Cancer Treatment

50 Things About 50 Cancers

This ebook from medical practitioner and family doctor Dr. Parajuli gives you all of the signs and symptoms that you need to know in order to catch cancer in the very early stages and protect yourself from it. You don't have to worry about if you have cancer anymore, and better yet you don't have to spend thousands of dollars to make sure of that either! All it takes is a bit of knowledge and you are on your way! This book also teaches about other aspects of cancer patients, such as how to live with different kinds of cancer, how to prepare yourself mentally to accept this reality if it IS a reality for you, and how to deal with doctors and insurance companies. This book is easy to read and in PDF format, so you don't have to worry at all about reading it. Make it easy on yourself! Read more...

Do I Have Cancer Overview

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Atlas of Staging in Gynecological Cancer

Richard Smith, MB, ChB, MD, FRCOG Consultant Gynaecological Oncologist West London Gynaecological Cancer Centre Hammersmith & Queen Charlotte's Hospital London UK British Library Cataloguing in Publication Data Atlas of staging in gynecological cancer 1. Generative organs, Female - Cancer - Atlases 2. Tumors - Classification I. Smith, J. Richard II. Healy, Jeremiah III. Del Priore, Giuseppe 616.9'9465

Utility of Adenoviral Vectors in Animal Models of Human Disease I Cancer

Animal Models of Lung Cancer 535 A. Human Lung Cancer 535 B. Animal Models of Human Lung Cancer 537 C. Gene Therapy of Lung Cancer Using Adenoviral Vectors 543 III. Animal Models of Human Prostate Cancer 547 A. Human Prostate Cancer 547 B. Spontaneous and Transgenic Models of Human Prostate Cancer 547 C. Xenograft Models of Human Prostate Cancer 548 D. Gene Therapy Approaches with Adenovectors in Prostate Cancer 550

Imaging studies and cervical cancer

Lymphangiography can be used to assign staging in the FIGO system. A computed tomography (CT) scan, MRI and a PET scan cannot be included in the FIGO staging procedure, but certainly change treatment decisions when available. These imaging studies are useful in accurately determining the extent of disease spread in order to tailor treatment for patients with cervical cancer. Advances in imaging could improve the accuracy of staging cervical cancer by facilitating the detection of lymph node and distant organ metastases. This procedure is rarely used when the modern alternatives described below are available because it is painful and operator dependent leading to questionable reliability.9

Imaging studies and cervical cancer continued

In the staging of cervical cancer, CT may be unofficially substituted for an intravenous pyelogram in the evaluation of ureteral obstruction. In addition, CT scans may provide information regarding tumour size, lymph node enlargement and the presence of distant metastases. CT and MRI have comparable accuracies in determining lymph node metestases in cervical carcinoma of 85-95 .10 Meta-analysis of published studies confirmed that CT and MRI performed to a similar degree of accuracy in the detection of lymph node metestases and slightly better than lymphangiography. A finding of enlarged lymph nodes on CT scanning has a specificity of 93 , but a positive predictive value of only 39 .9,10

Tumor Escape And Future Approaches To Cancer Immunotherapy

Notion that tumors might also be able to protect themselves from immune effector cells by inducing their death was both appealing and supported by the extensive evidence that these effector cells are dysfunctional in the tumor microenvironment (21,23, Table 1). It also provided a reasonable explanation for the noted limited success of adoptive immunotherapies employing activated effector cells in patients with cancer (53). However, it has now become necessary to convincingly demonstrate that the newly identified mechanisms leading to apoptosis of immune cells apply to tumor-effector cell interactions. If immune effector cells die in the tumor, and if the rate of their demise exceeds that of survival, then it might be surmised that tumor-induced apoptosis of immune cells might be an important prognostic parameter. This hypothesis has to be tested. The potential ability of immunotherapies to protect effector cells from apoptosis might be related to the clinical response of patients, and...

Cancer Vaccines That Elicit

Tumor-unique antigens occur randomly and unpredictably, either in genes or in their associated introns (86) or even in control-region sequences. Thus the number of unique peptides that could be associated with any given cancer is potentially huge. Moreover, the heterogeneity in class I structures within a population makes it difficult, even with non-mutated tumor proteins, to predict which peptides will interact well with individual MHC structures, or to prepare peptide cocktails that will cross-react with sufficiently large numbers of alleles to make this approach economically feasible. On top of all that, selected peptides must find CTL with cognate receptors to be effective as vaccines. In spite of these difficulties, some striking results have been obtained with this approach, and are discussed briefly herewith. Vaccine trials with peptides representing other cancers including breast (91), cervical (92), and pancreatic (93), are underway, and have given broadly similar results...

SUMO and Cancer Caretakers and Gatekeepers

Tumourigenesis is strictly limited to complex organisms with renewable tissues that contain dividing or proliferation competent cells. Cancer can be simplistically defined as a case of aberrant cell hyperproliferation that develops in post-natal tissues and causes organismal disorder that, in most cases, leads to the death of the organism. Complex organisms have evolved specific tumour-suppressor mechanisms to curb uncontrolled cell proliferation. The molecules involved in these mechanisms can be broadly divided into caretakers and gatekeepers 57 . Caretaker tumour suppressors act predominantly on the genome, in principle, by preventing, sensing and repairing DNA damage. Gatekeeper tumour suppressors, on the other hand, act on cells by regulating and implementing apoptosis or cellular senescence. Apoptosis kills and ultimately eliminates cancerous cells, while cellular senescence irreversibly arrests cell growth and thus immobilizes cancerous cells (for further details see, for...

Example Visualization of Gene Clusters in Bladder Cancer

Figure 6.8 is a visualization of the most important genes (selected by their co-variance to the progression of the disease) in DNA microarray measurements in bladder cancer patients. Fig. 6.8 Hierarchical clustering of genes (rows) expressed in bladder cancers (columns). Yellow fields show up-regulation of genes (absolute difference in right panel, logfold change in left panel), blue fields show down-regulation of genes. (Figure by Christopher Workman using ClustArray software on data from Thykjaer et al., (2001) and postprocessing with Adobe Illustrator). (See color plate.)

Susceptibility To Skin Cancer

Among the residents aged 60 or more years in the BFD-endemic area, the prevalence of skin cancer was 4.8 , 16.5 and 25.6 , respectively, for males whose drinking water had arsenic concentrations of < 300, 300-599 and > 600 Mg l (Tseng et al., 1968). The corresponding figures for females were 0.9 , 6.2 and 11.0 , respectively. However, the status of undernourishment in the development of arsenic-induced skin cancer was not examined in this study. In a recent survey in the BFD-hyperendemic villages, the prevalence of skin cancer was found to increase with the duration of consuming sweet potato in a dose-response relationship (Hsueh et al., 1995). The multivariate-adjusted odds ratios were 5.5 and 8.5, respectively, for those who consumed sweet potato for 10-19 and > 20 years compared with those that had a consumption duration of < 10 years. In another nested case-control study in BFD-hyperendemic villages, the incidence of arsenic-induced skin cancer was found to increase with...

Chromosomal Alterations in Cancer

Chromosomal alterations have been widely documented in the various forms of cancer, and some of these chromosomal aberrations are recognized to be causally related to cancer induction and or progression. In some cases, these alterations represent loss of individual chromosomes, chromosome arms, or specific chromosomal segments, consistent with deletion of a tumor suppressor locus. In other cases, these alterations represent gain of individual chromosomes or specific chromosomal segments, consistent with activation of a positive mediator of cell proliferation. In addition, numerous complex chromosomal rearrangements (such as translocation) have been characterized in certain forms of cancer. In each of these cases, the result is alteration of gene dose (either as gene loss or gene amplification) and function (altered product or altered expression). Cytogenetic methods to characterize chromosomal alterations have been applied for many years, but recent developments have automated this...

The Functional Aspect Of The Rna Continent In Cancer Research

Accumulation of somatic genetic alterations and subsequent clonal expansions leads the cells to a malignant neoplasia formation. The pathway progresses in a stepwise manner and is called multistep carcinogenesis (Fearon and Vogelstein, 1990 Nowell, 1976 Sugimura, 1992 Weinberg, 1989). Cancer cells acquire a variety of growth-advantageous features such as suppression of apoptosis and loss of anchorage dependence during the process of carcinogenesis (Hanahan and Weinberg, 2000). The major target of environmental carcinogens is the DNA. Many of the susceptible genes for hereditary cancer-prone diseases encode DNA repair genes. Therefore, the cancer is a disease of DNA. Somatic DNA alterations cause cancer. Because the central dogma is an almost ultimate paradigm in the molecular biology, cancer scientists mainly concentrated their attention to the protein-coding genes as susceptibility genes for cancer. Hence, they may not have paid enough attention to the possibility that RNAs are...

Mirna And Other Small Rnas In Cancer

In terms of carcinogenesis, miRNA has been known as an important player (Hammond, 2006 Zhang et al., 2007). The first report suggesting the involvement of miRNA in malignant neoplasms appeared in 2002 (Calin et al., 2002). Calin et al. showed that two miRNAs, miR-15 and miR-16, are frequently deleted or downregulated in B cell chronic lymphocytic leukemia (CLL) (in 68 of the cases). Both miRNAs are located within a 30-kb region at chromosome 13q14, a region deleted in more than half of the CLL cases (Calin et al., 2002). It is also indicated that many human miRNA genes localize at fragile sites and cancer-related genomic regions, suggesting the involvement of change of expression of miRNA in carcinogenesis (Calin et al., 2004). One of the major topics of miRNA in cancer is that let-7 miRNA may suppress the protein expression of the protooncogene RAS (Hayashita et al., 2005 Johnson et al., 2005). It is shown that the target of the let-7 family, let-60, is a homologue of RAS in C....

Carcinogenic Interactions For Smoking And Occupational Inhaled Arsenic

Table 3 provides three examples of carcinogenicity from arsenic and smoking (Pershagen et al., 1981 Enterline, 1983 Pershagen, 1985). The first shows that the relative risk for lung cancer, comparing retired arsenic smelter workers to the male population in the state where the study was conducted, among nonsmokers is 5.1. If we compare smokers to nonsmokers among the general population of males, the relative risk is 7.2. If the effects were multiplicative then we would expect the arsenic-exposed workers who were smokers to have a relative risk of about 35. The actual relative risk is 20.7, indicating that there is interaction on the multiplicative scale the effects of smoking and arsenic exposure are less than multiplicative. If we express these numbers on the additive scale, we obtain an excess relative risk (ERR) for arsenic exposure among nonsmokers of 4.1, an ERR for smoking in the general population of males of 6.2, and an expected ERR, under an additive model, of 11.3 (...

Anticancer Drug Discovfry Basfd On Biological Fndpoints

During the past year for which antitumor evaluation has not as yet been reported. However, a number of natural products identified by their cytotoxic activity have recently entered clinical trial. These include the first marine natural product, didemnin B (1), to be evaluated extensively in man (5). This cyclic depsipeptide may be of greater interest as an immunosuppressive agent in transplantation as its preclinical profile in tumor models is not outstanding (6, 7). Mechanistic studies suggest that didemnin B may act as an inhibitor of protein biosynthesis (8). Another natural product of interest both as an antitumor agent and immunosuppressant is deoxyspergualin (2) (9, 10). An analog of 2. was initially discovered in a screen for inhibition of focus formation in Rous sarcoma virus infected chicken fibroblasts (11). Compound 2 is in Phase I clinical trial in cancer patients (12) despite the finding that its preclinical antitumor activity is limited to leukemia models (9) its...

Carcinogenic Interactions For Ingested Arsenic

Numerous factors have been or might be hypothesized to interact with arsenic ingested from drinking water in increasing the risk of, or altering susceptibility to, cancer. Table 4 summarizes these. Below, we review evidence for such effect modifiers. Methylation capacity has been hypothesized to play a role in susceptibility to arsenic-induced carcinogenicity. Hsueh et al. (1997) classified subjects from a Taiwanese study according to the percent of arsenic excreted as monomethyl arsonic acid (MMA) in urine and also by cumulative arsenic exposure. These authors found that the multivariate adjusted odds ratios for skin cancer differed in these four groups. Within the low cumulative arsenic exposure group, those with a higher percentage of urinary MMA showed a relative risk of 3.0 compared to those with a lower percentage (< 26.7 ). Among those with a low excretion of MMA, a higher cumulative arsenic exposure was associated with an 8-fold increased risk of skin cancer. However, when...

Models of carcinogenesis

The simplest experimental model of carcinogenesis is the three-stage model consisting of initiation, promotion and progression.19 At the initiation stage, a single cell is thought to acquire a mutation and then divide repeatedly so that the mutation is passed on to a clone of daughter cells, thus forming a focal lesion that can survive and grow at the expense of neighbouring cells. During promotion, the normal constraints on proliferation and spatial organisation within the affected tissue are disrupted further, and the appearance of further mutations to proto-oncogenes and tumour suppressor genes leads to a progressive loss of differentiation and orderly growth. The genes involved in this transition to cancer, and the functions they perform, are under intensive investigation and are particularly well characterised in the intestinal epithelium.20 At the progression stage the lesion has made the transition to malignancy and can give rise to secondary tumours at remote sites. Animal...

Mechanismrasfd Anticancer Drug Discovery

Although cytotoxicity assays and animal tumor models still play a critical role in the evaluation of lead compounds and selection of development candidates, mechanism-based approaches are increasingly used for initial detection of leads and to guide synthetic efforts. Specific biochemical assays can be used to discover and develop cytotoxic drugs which work by mechanisms similar to those of established anticancer drugs e.g., production of DNA damage, inhibition of nucleic acid biosynthesis, or interference with tubulin function. Such approaches are also being employed to identify lead compounds which selectively interfere with the expression of oncogenes or the function of oncogene products demonstrated to play a role in the malignant phenotype. Topoisomerase Inhibitors - Among mechanism-based approaches to anticancer drug discovery, the design and synthesis of topoisomerase inhibitors has received a great deal of attention recently. Many of the clinically important anticancer agents...

Anticancer Drugs Can Induce Apoptosis

Studies performed over the past 15 years have demonstrated that virtually all the agents currently utilized to treat cancer can induce apoptosis (1), a morphologically and biochemically distinct cell death process (2), in susceptible cells. Morphologically, this process is characterized by plasma membrane blebbing, cell shrinkage, and chromatin condensation followed by disassembly of the cell into multiple membrane-enclosed fragments, which are then engulfed by neighboring cells or professional phagocytes (2). From Cancer Drug Discovery and Development Apoptosis, Senescence, and Cancer Edited by D. A. Gewirtz, S. E. Holt and S. Grant Humana Press Inc., Totowa, NJ Additional analyses have suggested that apoptosis also occurs after administration of antileukemic therapy in the clinical setting (6-10) and after treatment of solid tumors in certain animal models (2,11,12). These observations, which suggest that proximal effects of divers anticancer drugs can lead to activation of a common...

Matrix Metalloproteinase Inhibitors for Treatment of Cancer

Introduction Cancer is the second most common cause of death in the advanced countries approximately one in five persons will die of this disease. It imposes great cost on society and individuals via premature disability, mortality and high treatment costs. Despite advances in the diagnosis and management of the disease and billions of dollars spent in research, only modest improvements in cure and survival rate have been realized. The primary treatment approach has relied upon cytotoxic strategies to limit tumor growth and metastasis. However, cytotoxic drugs and radiation therapy often lead to unacceptable side effects. Although the exact mechanisms responsible for the formation of the tumors and the onset of metastasis are not fully understood, the critical event signaling the initiation of the metastatic cascade in tumor invasion is thought to be the interaction of the tumor with the basement membrane. The matrix metalloproteinases (MMPs) are documented to be involved in the...

Warning Signs of Colorectal Cancer

Colorectal cancer often has no warning signs. Because of this, your doctor will recommend regular screening with fecal occult blood tests (to check for blood in your stool) and colonoscopy (see Diagnostic Procedures, page 282). However, if you experience any of the following symptoms, see your doctor immediately Treatment for colon cancer depends on how far the cancer has advanced and may include surgery, radiation therapy, chemotherapy (treatment with powerful anticancer drugs), or some combination of these. Surgical removal of the tumor and surrounding colon and lymph tissue is the most common treatment for colon cancer. After the cancerous section of the colon has been removed, the healthy sections are reconnected. In some cases the surgeon may perform a colostomy (see box on next page) to provide an outlet for feces. If the tumor is large, you may need to undergo radiation therapy before surgery to help shrink the tumor. Radiation therapy also may be used after surgery to ensure...

Treatment Of Vulval Lesions Microinvasive vulval cancer

Micro-invasive vulval cancer, which is defined as a single lesion measuring less than 2 cm in maximum diameter and with a depth of invasion less than or equal to 1.0 mm, is usually managed by complete local excision of the lesion only. Invasive vulval cancer No clinical evidence of lymphadenopathy In stage I and II lesions with no clinical evidence of lymph node enlargement, a wedge biopsy is performed in order to assess the depth of invasion and rule out the presence of micro-invasive disease. If the depth of invasion is confirmed to be more than 1 mm then a radical local excision and unilateral inguinofemoral node dissection is the treatment of choice. Bilateral nodal dissection is indicated if the lesion is situated in the midline, if the labia minora are involved or there are positive ipsilateral lymph nodes. This is based on the observation that, in early lateral tumours, the incidence of positive contra-lateral nodes is less than 1 .2

Proteomic Applications in Cancer

As of today, expression proteomic studies are available for all common human cancers and some rare tumors. 5.1.1. Lung Cancer Proteomic studies in lung cancer, the most common cancer worldwide, have been reviewed 37 . Initial studies on lung cancer proteomics were first published in the early 1990s. These early studies focused on the relationship between histopathological characteristics and 2D-PAGE reproducibility 38 . A few years later, the first differentially expressed proteins in lung cancer were identified in small cell lung cancer (SCLC), including -tubulin, heat-shock proteins 73 and 90, lamin B, and proliferating cell nuclear antigen (PCNA). This report demonstrated for the first time that 2D-PAGE combined with protein identification was an effective approach to identify biomarkers in cancer 39 . Later on, with improvements in MS technology, it was possible to identify about 20 potential biomarkers in lung cancer tissue 40 . Recently, a SELDI study in early lung cancer stages...

Replication Competent Adenoviruses in Cancer Patients

Over the past century a diverse array of viruses were injected into cancer patients by various routes, including adenovirus, Bunyamwara, Coxsackie, dengue, feline panleukemia, Ilheus, mumps, Newcastle disease virus, vaccinia, and West Nile 1, 45-47 , These studies illustrated both the promise and the hurdles to overcome with oncolytic viral therapy. Unfortunately, these previous clinical studies were not performed to current clinical research standards, and therefore none give interpretable and definitive results. At best, these studies are useful in generating hypotheses that can be tested in future trials. treat 30 cervical cancer patients 47 . Forty total treatments were administered by either direct intratumoral injection (n 23), injection into the artery perfusing the tumor (n 10), treatment by both routes (n 6), or intravenous administration (n 1). Characterization of the material injected into patients was minimal. The volume of viral supernatant injected is reported, but...

What Has Been Achieved in Cancer Proteomics

Understanding Cancer Large-scale proteomic studies have addressed on a molecular basis the complexity of the alterations associated with transition from benign to malignant tumor cells that lead to appearance and progression of cancer. For example, proteomic-based studies of the effects of transforming growth factor (TGF)- in early and late stages of carcinogenesis have widened our knowledge of TGF- -dependent regulation of cell proliferation, apoptosis, DNA damage repair, and transcription (reviewed in 118 ). Another example of the utility of global protein expression approaches in understanding carcinogenesis is demonstrated by an extensive comparative survey of alterations found in breast epithelium during malignant transformation 119 . These include differences in levels of key regulators of the cell cycle, signal transduction, apoptosis, transcriptional regulation, and cell metabolism. The impact of proteomic approach was also demonstrated in a study that compared the...

Diet Nutrition And Cancer Historical Perspectives

It is abundantly clear that diet and nutrition are important contributors to carcinogen-esis, both in humans and laboratory animals (6-10). Evidence documenting the critical role of nutrition in cancer risk began to accumulate after the separate disciplines of carcinogenesis and experimental nutrition were established in the first half of this century. During this period, the essential nutrients were identified, requirements of rodents and humans were defined, and human deficiency syndromes corrected in industrialized nations. Purified nutrients and components of foods were characterized for the preparation of carefully controlled experimental diets in laboratory animals. Scientists proceeded to examine the effects of specific nutrients on tumorigenesis in the rapidly expanding l ist of newly characterized rodent cancer models that were originally based on carcinogens found in the environment, such as the workplace. The meticulous studies from the laboratories of Tannenbaum (11-13),...

Example I Classification Of Bladder Cancer Subtypes

As an example, our lab was faced with the problem of building a classifier that could categorize a bladder cancer as superficial or invasive based on a DNA chip test of a biopsy from the patient (Thykjaer et al., 2001). We only had biopsies from 10 patients. We decided to use a model without any estimated parameters at all. We simply measured the angle between the vector of all gene expression levels for each patient and the vectors of two reference samples of pools of superficial and invasive cancer. The angle was always smallest to the correct pool, because the vector angle distance was smallest EXAMPLE II CLASSIFICATION OF SRBCT CANCER SUBTYPES EXAMPLE II CLASSIFICATION OF SRBCT CANCER SUBTYPES

Thalidomide And Analogs In Angiogenesis And Cancer

Negative results using thalidomide have been reported in rodent cancer models (41,45). These studies did not, however, take into consideration that thalidomide is neither teratogenic nor antiangiogenic in rodents when administered orally. In contrast, other studies in mice have shown that thalidomide had small antitumor effects, and in combination with 5,6-dimethylxanthenone-4-acetic acid, an analog of flavone acetic acid, resulted in complete cures in mice (46). Mice treated with thalidomide administered by intraperitoneal route in combination with cytoxan and adriamycin showed significantly smaller tumors than those given the two chemotherapeutic agents alone in a model of breast cancer (47). Since the effects of thalidomide may be more accurately reflected in rabbits than rodent models, thalidomide was tested

Patterns of LOH in Cancers

LOH has been detected on all chromosomes. Table 11.1 summarizes some associations between LOH and cancers, and Table 11.2 lists individual genes that are targets for allele loss in cancers. The following sections outline in more detail selected research on LOH in disease, with particular focus on known or putative tumor suppressor genes and their role in disease initiation or progression. LOH at 1p has been associated several cancers, including lung,48-51 colorectal,52 and gastrointestinal stromal tumors5 3 and hepatocellular carcinoma.54 LOH at 1p36 was found to Table 11.1. Associations between loss of heterozygosity (LOH) and some cancers. Table 11.1. Associations between loss of heterozygosity (LOH) and some cancers. Cancers Lung cancer Bladder cancer Small cell lung cancer GPX1 (selenium-containing antioxidant enzyme) Von Hippel-Lindau (VHL) (inherited cancer predisposition) BRCA1, -2 HRPT2 gene CDH13 FHIT gene Head and neck, lung, breast, 141 and colon cancers Multiple organs can...

Gastrointestinal Tract Including Carcinogenesis

Chronic alcohol consumption is associated with an increased risk of cancer in the upper alimentary tract and the colorectum 109 , It might be possible that the production ofROS is involved in alcohol-associated carcinogenesis since chronic alcohol consumption leads to an induction of cytochrome P450 in the oral mucosa in the esophagus and in the colon of rodents 110,111 , Such an induction can also be demonstrated in the human oral mucosa 112 . In addition, the presence of xanthine oxidase has been located in the epithelial cells of the mouse and of the esophagus 113 . In an experiment by Eskelsson and co-workers, it has been shown that the number of esophageal tumors induced by nitrosamines and stimulated by chronic alcohol administration can be significantly reduced by the concomitant application of vitamin E 114 . Furthermore, this reduction is associated with a reduction in lipid peroxidation products in the esophagus. This is indirect evidence for the involvement ofROS in alcohol...

Mode Of Action For Dma Carcinogenesis In The

In the human, arsenic-induced skin carcinogenesis appears to involve hyperkeratosis associated with epidermal hyperplasia (IARC, 1980 Schwartz, 1997). It is unclear whether this is due to a direct mitogenic effect of inorganic arsenic on the epidermis or if it is due to toxicity and regeneration (Germolec et al., 1998). Since DMA is not directly DNA reactive, carcinogenesis in the rat bladder secondary to administration of high doses of DMA is likely caused by increased proliferation, either due to increased cell births or decreased cell deaths. There is no evidence that arsenicals have a direct effect on apoptosis or differentiation of the bladder epithelium of the rat. Therefore, it is most likely that the increased cell proliferation is due to an increase in cell births. This could be due to direct mitogenesis or toxicity followed by regeneration.

Ist To Monitor T Cell Directed Vaccine Trials In Cancer Patients

IST is a useful tool to evaluate the induction, localization, and phenotype of antigen specific CD8+ T cells in tissues after T cell directed vaccination of cancer patients. As discussed above, T cells specific for the tumor antigen survivin taken from melanoma and breast cancer tumors were shown to be cytolytic ex vivo (6). In contrast, recent studies of T cells specific for the MART tumor epitope showed that the tumor specific T cells had effector function in circulating blood but were functionally tolerant in tumor lesions (21). Findings such as these demonstrate that the functional status of T cells in blood does not always reflect the functional status in tissues and stresses the importance of in situ analysis of T cells in tissues.

Animal Models of Lung Cancer

Human Lung Cancer Lung cancer is the leading cause of cancer-associated mortality in both men and women. Although susceptibility to environmental carcinogens may be predetermined and follow a pattern of autosomal dominant Mendelian inheritance 2, 3 , lung cancer results from an accumulation of acquired genetic mutations 4-6 . In fact, it is suggested that 10-20 genetic mutations may be necessary for the development of lung cancer 7 , although the discrete steps for the progression of a hyperplastic bronchial lesion to metaplasia and anaplasia have not been uncovered. Tobacco use is the strongest epidemiologic risk for the development of lung cancer and it is anticipated that approximately 10 of all smokers will develop lung cancer over their lifetime 8 . Current paradigms predict that lung cancer results from the widespread exposure of the carcinogen, leading to a process of field cancerization, whereby the entire aerodigestive track is exposed to the offending agents and leads to...

Animal Models of Human Prostate Cancer

Human Prostate Cancer After lung cancer, cancer of the prostate (CaP) is the second most common cause of cancer death in American males. A latent disease, many men have prostate cancer cells long before overt signs of the disease are apparent. The annual incidence of CaP is over 100,000 in the United States, of which over 40,000 will die of the disease. Nearly a third of patients present with locally advanced or metastatic disease, and androgen deprivation therapy forms the basis of conventional therapy for the majority of these patients. However, currently available approaches for advanced CaP are not curative 137 , primarily because the cells lose their dependence on androgenic stimulation. The mechanisms of progression of CaP cells to hormone independence under androgen ablation therapy remain unclear. To investigate the factors and mechanisms that underlie the development of androgen resistance and metastasis, reliable in vivo models that mimic human CaP progression are...

Tumor classification for tailored cancer therapy

Introduction - Cancer is an unmet clinical disease that remains the second largest killer in the Western world, with a steady rise in both the occurrence and death rates due to cancer throughout the last century. Cancer is a genetic disease which, together with its multi-stage nature and the realization that many environmental and dietary factors can influence the disease, has wide ranging implications for its treatment and prevention in the 21st century. Although chemotherapy is currently the most promising treatment in clinical use, its success is greatly limited by a severe lack of understanding of tumor biology. This leads to an inability to predict the response of a given tumor type to a particular treatment regime, and consequently a considerable failure rate in clinical oncology. The inherent heterogeneity of tumors makes classification frequently difficult and often impossible. Current methods for classifying tumors rely on pathological and clinical diagnosis to determine the...

Detection of Circulating Prostate Cancer Cells by Measurement of PSA mRNA

Amplification of organ-specific mRNA by reverse transcription-polymerase chain reaction (RT-PCR) is a powerful method for detection of circulating prostate cancer cells. Many groups have reported detection of PSA mRNA in circulating cells by measurement of PSA mRNA by RT-PCR 173 and this approach is potentially useful for evaluating the prognosis of prostate cancer. It has been suggested to improve preoperative staging and prognosis of prostate cancer 174, 175 by identifying preoperatively organ-confined and extracapsular cancers, respectively 176-178 . However, at present it is not clear whether PSA mRNA levels correlate with tumor stage and grade 179 . By RT-PCR even one circulating PSA expressing cell among more than 100 million other cells may be detected 180,181 . However, the method is prone to methodological problems and false-positive results have been found to be caused by low background expression of prostate-specific genes in normal hematopoietic tissues and blood cells...

Cancers of the Respiratory Tract

Macchiarini et al. (79) first assessed whether the degree of angiogenesis correlates with metastasis in nonsmall-cell lung cancer (NSCLC). They determined intratumoral microvessel density in a series of 87 patients with initial tumor stage T1N0M0 who underwent radical surgery. The 22 patients who developed recurrence during the follow-up period had tumors with a statistically higher vascularization, compared to those alive and disease-free. Seven subsequent studies (80-86) investigated the prognostic significance of vascularization in NSCLC, and, in all the series, the patients with radically resected, highly vascularized primary tumors had poorer prognosis, compared to those with low angiogenic tumors (Table 4). Of particular interest were the studies by Apolinario et al. (84), suggesting that the prognostic value of neovascularization is more relevant in patients with stage II disease, and that the degree of angiogenesis was not related to the other biological (p53, bcl-2, and bax...

Cancers of the Genitourinary Tract

Much more information is available on the association of microvessel density with stage disease in prostatic cancer (91-98) (Table 5). Wakui et al. (91) first reported that the blood capillary density ratio, as assessed by a marker antivimentin, was predictive of bone marrow metastasis. All the other authors (91-98) who performed the subsequent Several authors also evaluated the expression of angiogenesis factors, such as VEGF, fibroblast growth factors (FGFs), TP, hepatocyte growth factor (or scatter factor), and pleiotrophin in human cancer of the bladder (reviewed in ref. 102). The most important factors mediating angiogenesis in such a tumor seem to be acidic and basic FGFs, VEGF, and TP. A differential expression of VEGF and TP in superficial and invasive cancers suggests that different angiogenic pathways may occur at different stages of this neoplasm.

Mechanisms relating adiposity to cancer risk

Body weight has strong effects on metabolic factors that may subsequently affect cancer risk in particular, on circulating levels of peptide and steroid hormones and their binding factors. Specific effects vary somewhat by gender and by menopausal status in women and are summarized in Table 2. Insulin-like growth factors (IGFs) are mitogens that regulate energy-dependent growth processes (14). IGF-I stimulates cell proliferation and inhibits apoptosis and has been shown to have strong mitogenic affects in a wide variety of cancer cell lines. The synthesis of IGF-I and its main binding protein, IGFBP-3, are regulated primarily by pituitary growth hormone (GH). In the circulation, more than 90 of IGF-I is bound to IGFBP-3. Obesity and other conditions related to chronic hyperinsulinemia result in elevated blood glucose levels, decreased levels of IGF-binding proteins (IGFBP-1 and IGFBP-2) and higher levels of free plasma IGF-I, the small fraction of IGF-I unbound to any binding protein....

Cancers of the Digestive Tract

The prognostic value of microvessel density was little investigated in esophageal cancers. The study by Kumano et al. (103) suggested a significant association of high vascularization with the expansive and down-growth patterns of tumor growth patterns. Moreover, both carcinoma in situ and microinvasive cancers had higher microvessel counts, compared to the adjacent normal mucosa. Tanigawa et al. (104) stained intratumoral microvessels of 43 esophageal squamous cell carcinomas with anti-CD34 and fVIII-RA antibodies. Both the markers were found to be significant and independent prognostic markers. Regarding gastric carcinomas, the studies by Maeda et al. (105) and Tanigawa et al. (106) found that tumor angiogenesis was predictive of recurrence and time to progression and overall survival, respectively, in patients with invasive gastric carcinomas. Microvessel density was found to be significantly higher in VEGF-positive gastric carcinomas than in those VEGF-negative. Moreover, the...

Cancers of Head and Neck

Albo et al. (117) studied angiogenesis in a small series of patients with squamous cell carcinomas of the head and neck, using fVIII-RA to stain microvessels. They found that the patients with highly vascularized primary tumors had a significantly higher frequency of recurrent or metastatic disease than those with low angiogenic cancers. A subsequent study by Williams et al. (118) found that angiogenesis is a significant prognostic indicator of recurrence in a series of 66 patients with oral cavity tumors. Gasparini et al. (120) determined several predictive and prognostic markers in 73 patients with head and neck squamous cell invasive carcinoma, who were treated with concurrent cisplatin or carboplatin and radiation therapy for stage II-IV disease. Vascularization was assessed by the anti-CD31 antibody, and it was significantly predictive of the probability of response to therapy, but not of prognosis. The patients with highly vascularized primary tumors had a significantly lower...

Evaluation by the International Agency for Research on Cancer

An International Agency for Research on Cancer (IARC) Working Group on the Evaluation of Cancer-Preventive Strategies published a comprehensive evaluation of the available literature on weight and cancer that considered epidemiological, clinical, and experimental data (18). Their 2002 report concluded that there is sufficient evidence in humans for a cancer-preventive effect of avoidance of weight gain for cancers of the endometrium, female breast (postmenopausal), colon, kidney (renal cell), and esophagus (adenocarcinoma) (18). Regarding premenopausal breast cancer, the report concluded that available evidence on the avoidance of weight gain suggests lack of a cancer-preventive effect. For all other sites, IARC characterized the evidence for a cancer-preventive effect of avoidance of weight as inadequate in humans. The conclusions regarding the evidence in humans are based on epidemiological studies of overweight and or obese individuals compared with leaner individuals, not on...

Complications of Anemia in Cancer Patients

The complications of anemia in the older cancer patient may include Fatigue and functional dependence. Fatigue is a feeling of tiredness unrelated to physical activity and not relieved by rest (24). It is the most common chronic symptom both of cancer and of chemotherapy, and is associated with serious consequences in the life of the patient and his her caregivers, including reduction of working hours and even inability to work. Approximately 40 of cancer patients and 20 of their caregivers had to quit working or take leave from work because of the patient's fatigue (24). Fatigue is clearly related to anemia correction of anemia relieves the fatigue of the majority of cancer patients and improves their quality of life (2). In older patients, anemia is also associated with increased risk of functional dependence, that is need of external help to carry on the basic activities of daily living (ADL) or the instrumental activities of daily living (IADL) (25-29). In older cancer patients...

Hematopoietic Cancers

Several studies have examined the relationship between hematopoietic cancers and BMI, but results from most of these studies are based on relatively small numbers of events. Still, most of the available studies have observed modest obesity-associated Fig. 1. Summary of mortality from cancer according to body mass index for US men in the Cancer Prevention Study II, 1982 through 1998. For each relative risk, the comparison was between men in the highest BMI category (indicated in parentheses) and men in the reference category (BMI 18.5 to 24.9). Asterisks indicate relative risks for men who never smoked. Results of the linear test for trend were significant (p < 0.05) for all cancer sites. Reproduced with permission from ref. 3. Fig. 1. Summary of mortality from cancer according to body mass index for US men in the Cancer Prevention Study II, 1982 through 1998. For each relative risk, the comparison was between men in the highest BMI category (indicated in parentheses) and men in the...

Overweight obesity and cancer mortality

Recent results from a large American Cancer Society prospective mortality study illustrate that increased body weight is associated with increased death rates from all cancers combined and for cancers at multiple specific sites in both men and women (Figs. 1,2). These results were based on a population of more than 900,000 US adults who were followed from 1982 through 1998, and on more than 57,000 deaths from cancer that occurred during the 16-yr follow-up period (3). The results are based on cancer mortality and thus may reflect the influence of BMI on either cancer incidence or survival, or both. Fig. 2. Summary of mortality from cancer according to body mass index for US women in the Cancer Prevention Study II, 1982 through 1998. For each relative risk, the comparison was between women in the highest BMI category (indicated in parentheses) and women in the reference category (BMI 18.5 to 24.9). Asterisks indicate relative risks for women who never smoked. Results of the linear test...

Retinoic Acidinterferona Combination Cancer Therapy

Retinoids and interferons (IFNs) show clinical promise in several carcinogenic settings. Retinoids have demonstrated significant clinical activity in randomized chemopre-vention trials in the head and neck, skin, liver, and cervix (82-90). Interest in retinoids for cancer therapy was greatly stimulated by the high complete response rate of acute promyelocytic leukemia (APL) to all-trans-retinoic acid (ATRA) (91-93). Retinoids have shown activity in certain other hematologic malignancies as well (10,94,95). In general, however, ATRA and other retinoids have disappointing single-agent results in established cancers. There are data indicating that 13cRA and ATRA may improve the antitumor efficacy of radiation, cisplatin, and IFN (96-105). achieved encouraging results in locally advanced untreated cervical cancer (112-114), squamous cell carcinoma (SCC) of the skin (115,116), and renal cell carcinoma (117). Combined 13cRA and IFN-a has achieved an overall major response rate of 45 in 55...

Molecular Genetics of Cancer Syndromes

. . . some combinations of genes yield bodies that are much more prone than others to break out into that unregulated growth that is called cancer. Cancer is a disease of growth (sometimes visible more characteristically, inside), of abnormal, ultimately lethal growth that is measured, incessant, steady. . . . Cancer's a funny thing. Nobody knows what the cause is, Though some pretend they do It's like some hidden assassin Waiting to strike at you. FEW diseases cause as MUCH DREAD and grief as cancer. Everyone knows someone who has died of cancer. A university professor at the prime of his career has blurred vision and headaches, goes to the doctor, is diagnosed with a brain cancer, glioblastoma, and despite therapy dies within two years. A tennis player is unusually fatigued, goes to the doctor, is diagnosed with chronic myeloid leukemia (CML), and although therapy prolongs his life, he dies nine years after onset of the cancer. A mother feels a continual soreness in the abdominal...

Cell Proliferation and Cancer

The formation of many cells (multicellularity) from a single fertilized egg involves a complex, highly coordinated series of processes that include cell proliferation, cell quiescence, apoptosis, and activation of dormant cells by extracellular factors. After embryogenesis, under normal conditions, most of the cells are in a nondividing, quiescent state called G0. Some continue to divide as needed, and apoptosis ensures that there is not an excessive accumulation of cells in any tissue or organ (Figure 16.1). Dozens of different proteins are required to induce or constrain cell proliferation, maintain or prevent cell division cycles, and initiate or inhibit apoptosis. Cell proliferation is triggered by a cascade of activation and inactivation steps, which, for the most part, are mediated by protein kinases that phosphorylate tyrosine, threonine, or serine residues of cytoplasmic and nuclear proteins. The nuclear proteins usually are transcription factors that collectively regulate the...

Life On The Edge Alterations In The Apoptotic Machinery In Cancer Cells

Because transforming oncogenes activate the intrinsic apoptotic pathway when cells encounter unfavorable growth conditions (242,243), it is perhaps not surprising that the intrinsic pathway is inhibited in a number of different ways in various cancers (233-245). Antiapoptotic Bcl-2 family members are overexpressed in some cancers (15,246,247). In others, constitutive activation of the mitogen-activated kinase pathway (139) induces activation (Bcl-2) or stabilization (Mcl-1) of group I Bcl-2 family members (see Section 7). In leukemia cell lines (248) and a substantial portion of mismatch repair-deficient colon and gastric cancers (249), the BAX gene is mutated, although the heterozygous nature of these mutations in clinical cancer (249) stands in contrast to results obtained in animal models (250) and by itself fails to completely account for any apoptotic defect. In other tumors, changes that upregulate the Akt pathway (251), including autocrine or paracrine activation of receptor...

Genetic Polymorphisms And Cancer Heterogeneity

Failed to convincingly identify a correlation between HLA phenotype, immune responsiveness and toxicity (18). Extended studies based on polymorphism of lymphokines, chemokines and their receptors have demonstrated an association in individual susceptibility to immune pathology, survival of transplanted organs or predisposition to cancer (19 20) (21-23) (16). The vast majority of polymorphism found in cytokine genes and their receptors are located in the promoter, intronic and 3' untranslated regions. The sequence variances occurring in untranslated regions of the gene can, however, still affect gene expression and function. In addition, promoter polymorphism may disrupt or abolish binding of regulatory elements such as NF-AB, Jak, STAT and other molecules involved in signal transduction pathways. Furthermore, some of this molecules central to cytokine expression levels are polymorphic themselves. Finally, intronic variation may affect enhancer silencer sequences and certain...

The Relationship of IgE to Cancer

In what may be a myth, there exists a poorly founded notion among some physicians that allergic people may be more resistant to certain forms of cancer. This concept was initiated by a report of Cockroft et al. in 1979, which summarized a comparative survey of 392 patients with three types of malignancy and 303 controls and concluded that the patients with endodermal neoplasia (lung, gut, bladder, prostate) had lowered forms of allergic disease. The major weakness of the survey was that the sample sizes were too small to be significant. In two other notable surveys done in later years with larger patient populations, the results were largely either contrary to the earlier study or too variable to make definitive conclusion. An in-depth analysis of the data concerning the occurrence of tumors among patients treated with omalizumab is especially pertinent. Malignancies were found in 20 of 4127 (0.5 ) of patients exposed to anti-IgE compared to 5 of 2236 (0.2 ) of patients exposed to...

The Impact Of Genetic Variation And Cancer Heterogeneity On Immune Responsiveness

As we previously discussed, genetic background may influence immune responsiveness. However, the genetic background of patients has not been extensively scrutinized as a predictor of immune responsiveness (16). Obvious genetic markers that may affect immune responsiveness are the HLA complex that codes for molecules responsible for antigen presentation to T cells (51). However, correlates between HLA phenotype and treatment outcome or survival failed to provide conclusive evidence that individual variability in antigen presentation may determine immune responsiveness in the context of anti-cancer immune therapy (18 52 53). Others have pointed to other polymorphisms as harbingers of immune responsiveness. For instance polymorphisms of the IL-10 gene appears to be responsible for differential levels of expression of this cytokine in various conditions. Interestingly, individuals with a phenotype associated with low IL-2 production appear to bear an increased incidence of melanoma and...

Dynamic Monitoring Of Anticancer Immune Responses

Although genetic background may be responsible for immune responsiveness, it is also possible that the unstable nature of cancer cell phenotypes can strongly influence the susceptibility of cancerous lesions to immune attack. In fact very little is known about the algorithm that may determine the occurrence of immune-induced cancer regression in humans (56). The introduction of gene profiling arrays is particularly suited to circumstances when little is known about a biological event to conceive plausible hypotheses. This is clearly the case of immune-mediate cancer rejection. We tested whether global transcript analysis could segregate lesions likely to respond to immunotherapy by obtaining FNA from subcutaneous melanoma metastases prior to immunotherapy (49). This work was based on a previous observation suggesting that cutaneous melanomas can be segregated into two distinct taxonomies based on global transcript analysis (57). Such observation stimulated the question of whether two...

Oncogenicity And Role Of Hpv In Human Cancers

Common warts and plantar warts never become malignant. Direct conversion of condylomas to carcinomas has been described anecdotally but is extremely rare. In addition to experimental evidence, large-scale epidemiological studies performed during recent years have established HPV infections as the major risk factor for cervical cancer. Skin cancers arising in immunosuppressed patients are also increasingly found to contain HPV DNA. Since the matter of causality is being elucidated, the focus is at present, and in the years to come, being shifted towards the mechanisms by which the interplay between certain HPV genotypes, the infected host cells, their environment and other factors may initiate, establish and maintain oncogenic processes in the cervix as well as other locations. HPVs associated with anogenital lesions have been divided into 'low-risk' types (6, 11, 34, 40, 42, 43) or 'high-risk' types (16, 18, 31, 33, 35, 39, 45, 51, 52, 54, 56, 58) based on the preneoplastic character...

Abarelix Anticancer [68

Abarelix is an antagonist of the gonadotropin releasing-hormone (GnRH) receptor, and it was launched last year as an intramuscular injection for the palliative treatment of advanced symptomatic prostate cancer. Hormonal therapy of prostate cancer is based on the modulation of testosterone to achieve medical castration levels. The inhibition of GnRH activity causes the suppression of luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion, thereby reducing the secretion of testosterone by the testes. Abarelix is the first GnRH antagonist to reach its market. Hormonal therapy with GnRH agonists such as leuprolide, buse-relin, and goserelin has been in use for over two decades. Drugs of this type achieve the suppression of LH and FSH by a feedback inhibition mechanism, which involves an initial rise in the LH and FSH levels and, consequently, in the levels of testosterone. A testosterone surge may induce a clinical tumor flare that worsens cancer-related symptoms. This...

Bevacizumab Anticancer [1822

Bevacizumab, a humanized IgGl monoclonal antibody against vascular endothelial growth factor (VEGF), inhibits tumor angiogenesis and delays disease progression. It was launched in the US last year as an intravenous infusion for the treatment of metastatic colorectal cancer in combination with fluorouracil-based chemotherapy. Bevacizumab was developed by engineering the VEGF binding residues of the murine neutralizing antibody A.4.6.1 into the framework of the consensus human IgGl. Its amino acid sequence is approximately 93 human IgG and 7 murine antibody and is produced in a CHO cell expression system. Bevacizumab binds VEGF with high affinity (Kd 0.5 nM) and prevents its interaction with tyrosine kinase receptors VEGFR1 and VEGFR2 on the surface of endothelial cells, thereby inhibiting cell proliferation and microvascular growth. In mouse models, administration of bevacizumab blocked the growth of human tumor xenografts and reduced the size and number of metastases. The recommended...

Gene Expression Assays in Cancer

The technology and expertise required for analysis of gene expression were adopted at a very early stage in its development by the field of cancer biology. This was because it was recognized that, while there were available a number of useful clinical, morphological, and molecular parameters for diagnosis and or prognosis of human malignancies 36 , there remained a substantial margin of error. It can be the case that, even with these tools, patients receiving the same diagnosis can have markedly different treatment outcomes. Cancer diagnosis is often subject to subtyping of diagnostic categories as new diagnostic tools are developed. There was a pressing need for a diagnostic tool which would complement existing histopathological evaluation and enable the profiling of cancer cells in tissues 37 . In addition to providing accurate diagnosis, there was a further need to provide biomarkers which would be useful in (1) detecting cancerous cells early in the disease, (2) providing accurate...

Oncogenicity And Role In Human Cancers

Fully permissive host cells are usually killed by polyomavirus infection. Infected cells that have the viral tumour antigen expressed, and survive, may become immortalized and malignantly transformed. Large T-antigen contributes to this by at least two sets of activities as a host-cell transcription factor and by complexing with and inactivating the tumour suppressor p53 as well as the retinoblastoma gene product pRB, and probably also other host proteins that regulate cell cycle progression and growth. Small t-antigen also acts as a transactivating factor, most probably by complexing with and inactivating protein phosphatase 2A, a mechanism which keeps important intracellular signal transduction pathways active. The oncogenic potential of primate polyomaviruses is evident by infection of rodents, while in the authentic host systems the viruses seem to require cofactors to be transforming. Human polyomaviruses are certainly not the cause of any human cancer. To what extent some viral...

Lapatinib Anticancer [4347

Lapatinib, a new member of the 4-anilinoquinazoline class of RTK inhibitors (RTKIs), was launched last year as an oral treatment for breast cancer. Lapatinib has dual affinity for EGFR and HER2 tyrosine kinases. It is indicated in combination with capecitabine for treating patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab. Previously marketed drugs from the 4-anilinoquinazoline class include erlotinib (Tarceva ) and gefitinib (Iressa ), both of which are indicated for treating non-small-cell lung cancer (NSCLC). As with erlotinib and gefitinib, lapatinib is an ATP-competitive kinase inhibitor. It inhibits the tyrosine kinase activity EGFR and HER-2 with apparent Kj values of 3 and 13 nM, respectively, and has slow off-rate kinetics (ti 2X300min). Oral absorption of lapatinib is incomplete and variable. Peak plasma concentrations (Cmax) are achieved approximately 4 h...

Cancer Risk Reduction

An overwhelming body of data across species has demonstrated the potency of AFB1 as a carcinogen and mutagen.32 The best evidence indicating an interaction between hepatitis B virus (HBV) and aflatoxin in human liver cancer has come from a cohort study in Shanghai, China, involving more than 18,000 men.54 5674 Assays for urinary AFB1, its metabolites AFP1 and AFM1, DNA adducts, and hepatitis B surface antigen (HBsAg) status have been undertaken. Subjects with liver cancer were significantly more likely than controls to have detectable concentrations of the aflatoxin compounds. Positivity for HBsAg was strongly associated with liver cancer risk. Thus, aflatoxin exposure in the presence of a persistent HBV infection increases the risk of human liver cancer.28 Such factors as unknown genetic and host response interactions may play a role in the liver cancer HBV AFB interaction.28 33 Evans et al.20 compared three independent cohorts of male HBsAg carriers in Senegal, in Haimen City,...

G cmyc as Target for Anticancer Therapy

Transductions) or in the signal transduction pathways that regulate c-myc expression (Marcu et al., 1992 Spencer and Groudine, 1991). Since in normal cells c-Myc induces apoptosis in the absence of sufficient amounts of survival factors (Askew et al., 1991 Evan et al., 1992) activation of the oncogene c-Myc strongly selects for a second mutation that eliminates an apoptosis pathway (e.g., p53) or for activation of a second cooperating oncogene that inhibits apoptosis and stimulates cell survival (e.g., Bcl-2, Bcl-xL, Ras) (Nilsson and Cleveland, 2003 Oster et al., 2002). However, if c-Myc-induced apoptosis is suppressed (e.g., by coexpression of the anti-apoptotic proteins Bcl-xL or Bcl-2 or by an excess of local survival factors) c-Myc activation alone is sufficient to trigger immediate carcinogenic progression in the absence of other cooperating oncogenic lesions (Luo et al., 2005 Pelengaris and Khan, 2003a Pelengaris et al., 1999, 2002a,b). Vice versa, inactivation of the oncogene...

In Vivo Fluorescence Endomicroscopy in Cancer Treatment

Imatinib is a well-established chemotherapeutic agent of kinase-targeted treatment that has found increasing use in cancer treatment. Approximately > 90 of gastrointestinal stomal tumours (GIST) express the CD 117 (c-kit) antigen and have mutations in the corresponding gene, and a large majority of GIST patients benefit from treatment with imatinib, which is the main therapeutic modality in this disease. Therefore, in vivo fluorescence endo-microscopy detecting CD 117 in these tumours could be an effective method to identify which patients would benefit from imatinib therapy 19 . Other possible applications for in vivo fluorescence endomicroscopy might be the assessment of the epidermal-growth-factor-receptor (EGFR) expression in therapy-refractory colorectal carcinoma, which could stratify the patient population eligible for cetuximab treatment 20 .

Belotecan Anticancer [1417

Belotecan, a DNA topoisomerase I inhibitor, is an analog of camptothecin. It was launched last year in the Republic of Korea as an injectable formulation for the treatment of ovarian and small cell lung cancer. Although camptothecin exhibits potent antineoplastic activity in vitro, its clinical application is hampered by severe toxicity and poor water solubility. Several synthetic and semi-synthetic analogs of camptothecin with improved solubility and lower toxicity have been developed over the past two decades. Two drugs from this class, topotecan and irinotecan, have been launched in previous years and belotecan is the newest member to reach the market. It is prepared by a two-step semi-synthesis starting from camptothecin, first by converting to 7-methylcamptothecin via a free-radical methylation reaction using a combination of acetic acid, tert-butylhydroperoxide, ferrous sulfate and sulfuric acid, and subsequently, in the second step, a Mannich reaction with is-opropylamine...

Gene Mutations in Cancer

Mutations affecting a variety of genes have been characterized in cancer. Some of these mutations represent activating mutations of proto-oncogenes (or other positive mediators of cell proliferation) and others represent inactivating mutations of tumor suppressor genes (or other negative mediators of cell proliferation). Mutations in these genes synergize with other genetic (chromosomal) and epigenetic abnormalities to drive neoplastic transformation and tumorigenesis in affected cells and tissues. This review focuses on the mutation of ras and p53 in cancer. Mutation of the ras Gene Family in Cancer Each of these ras family of oncogenes have been found to be mutated with varying frequencies in major forms of human cancer. 1 30 K-ras is mutated in cancers of the lung, colon, and pancreas, as well as in myelodysplastic syndrome and some other cancers (such as seminoma). The frequency of K-ras mutation in pancreatic cancer is estimated to be 90 ,130 suggesting that this gene mutation is...

Talaporfin Sodium Anticancer [9195

In collaboration with Light Sciences Corp. and Meiji Seika Kaisha, Nippon Petrochemicals has developed and launched the injectable photosensitizer talaporfin sodium in Japan for the photodynamic therapy (PDT) of cancer. The initial approval is for the treatment of early stage lung cancer, but Light Sciences Corp. and its subsidiaries are also developing talaporfin sodium for other hyperproliferative diseases, such as, liver metastases arising from colorectal cancer, wet age-related macular degeneration, and atherosclerosis. Talaporfin sodium is typically supplied as a lyophilized green powder, and it is synthesized via a carbodiimide-mediated coupling of chlorin e6 (obtained from precursors that were extracted from natural sources) with L-aspartic acid. Since chlorin e6 contains three carboxylic acid groups, the coupling reaction produces a mixture of aspartic acid conjugates. The desired site of conjugation is the acetic acid side chain of C-20, and the other regioisomers are removed...

Dma Carcinogenesis In Rats

A major impediment to furthering our understanding of the mechanisms by which arsenic causes cancer in humans has been the lack of appropriate animal models (IARC, 1980 Huff et al., 2000). Despite its recognition as a human carcinogen, the various forms of arsenic have not been widely tested in animal models, including in standard two-year bioassays. However, recently, administration of relatively high doses of dimethylarsinic acid (DMA) were demonstrated to produce an increased incidence of cancer of the urinary bladder in rats, with females apparently more susceptible than males (van Gemert and Eldan, 1998 Wei et al., 1999). Bladder tumors were induced whether the chemical was administered in the diet (van Gemert and Eldan, 1998) or in the drinking water (Wei et al., 1999). Administration of DMA in drinking water appeared to produce a significantly greater toxicity at comparable doses. Nevertheless, the only tissue showing any incidence of tumors after two years in the rat was the...

ARCAs for Prostate Cancer CV706 and CV787

There are several criteria important in regard to the transcriptional response element (TRE) necessary for the successful engineering of a therapeutic adenovirus (1) the tissue-specific regulatory specificity must be tightly regulated, and transcription should be limited to tumor cells, or accessory cells with as few other sites of expression as medically tolerable, (2) the TRE must regulate the initiation of transcription of the adjacent gene, (3) the promoter must be strong enough to drive sufficient expression of essential viral genes, and (4) the TRE must be small enough to fit within the packaging limits of adenovirus. We chose prostate cancer and the TREs of PSA as our initial target. To test the feasibility of the ARCA technology, we engineered the PSE fragment into the adenovirus genome and generated a first generation virus, CV706. CV706 contains the PSE fragment (PSA promoter and enhancer) inserted immediately upstream of the El A region and transcription of the E1A region...

MMPs Identified in Urine of Patients with Cancer

Gelatin zymography has been used to demonstrate the presence of several forms of MMPs in the urine of patients with cancer. The potential for using this test for early diagnosis or staging of cancer has been proposed. In a subsequent study, Moses et al. (M16) reported that MMP-2 and MMP-9 in urine correlated with the presence of malignant disease, not just limited to the genitourinary tract. The presence of biologically active MMP-2 or MMP-9 alone in the urine was an independent predictor of organ-confined cancer the higher molecular weight MMP species (> 150 kDa) in the urine served as independent predictors of metastatic cancer (M16). The frequency of detection of the three MMP species in the urine was as follows normal or no evidence of disease (11-20 ), cancer (71 ), metastatic cancer (90 ). The frequency of urinary MMPs was significantly higher in patients with prostate and breast cancer, 75 and 100 , respectively. Odds of metastatic cancer were 30 times greater when the higher...

Hereditary Nonpolyposis Colorectal Cancer

Hereditary nonpolyposis colorectal cancer (HNPCC, Lynch syndrome), which affects about 1 in 200 individuals, is the most common inherited cancer syndrome. It behaves as an autosomal dominant trait. The phenotype is characterized by few colonic polyps (< 100) and early onset of multiple tumors in the In the early 1970s, when chromosome banding was a newly developed technique, Janet Rowley (b.1925) demonstrated the first consistent association between a chromosome translocation t(8 21)(q22 q22) and a cancer (acute myeloblastic leukemia, AML). Shortly afterward, she solved the mystery of the Philadelphia chromosome (Ph'). Since 1960, the Philadelphia chromosome, named after the city where it was first discovered, had been observed consistently in cases of chronic myeloid leukemia (CML). On the basis of whole chromosome staining, the Philadelphia chromosome appeared to consist of half of either chromosome 21 or 22. At this level of resolution, there was no evidence that it was part of a...

Colon Polyps A Warning Sign for Cancer

The most common type of polyps are hyperplastic (high-per-PLAS-tik) polyps. These are benign (beh-NINE) - ''kind'' or non-cancerous polyps -that simply represent an ''excessive or above normal'' (hyper-) ''formation'' (-plasia) of epithelial cells. This type never evolves into colon cancer, but can cause rectal bleeding if they become too large. The polyps that are dangerous are called adenomatous (ad-eh-NOH-mah-tus) polyps. These are literally ''gland'' (aden) ''tumors'' (-omas) that are shaped like little ''feet'' (polyps). Although the adenomatous polyps themselves, are benign, they are considered precancerous polyps that, if left to grow long enough, can develop into full-blown cancer of the colon. ''little tubes'' (tubul). This highly unusual mixture of abnormal cellular patterns is the probable forerunner of colon cancer. Everyone is recommended to have a routine screening colonoscopy by age 50, or much earlier, if a history of colon cancer runs in the family, or if rectal...

Beyond Kinases Purine Binding Enzymes as Cancer Targets

Heat-shock Protein 90 (Hsp90) - Hsp90s are ATP-dependent molecular chaperones that are preferentially over-expressed (2-10 fold) in some cancer cells (4). Crystallographic studies have revealed the existence of a non-conventional low affinity ATP binding cleft at their N-terminal domain that is well-conserved among the four family members Hsp90 a and p, Grp94 and Trap-1 (5). The occupancy of the ATP binding site by the ansamycin antibiotics geldanamycin (GM), 1_, and herbimycin A (HA), 2, as well as the structurally unrelated fungal metabolite radicicol, 3, inhibits the intrinsic weak ATPase of Hsp90, and results in simultaneous destabilization and eventual ubiquitin-dependent degradation of its client proteins (69). Uniquely, many of the Hsp90 client proteins are well-known oncoproteins that are frequently mutated or over-expressed in cancer cells, such as the mutated p53, Bcr-Abl, Raf-1, Akt, ErbB2, and steroid receptors (9). The association with Hsp90 allows these otherwise...

Emerging Microtubule Stabilizing Agents for Cancer Chemotherapy

Introduction - The discovery of the potent anti-cancer properties and subsequent elucidation of the mechanism of action of paclitaxel firmly established this compound as a leader in the treatment of difficult cancers. In addition, the unusual mechanism of action of paclitaxel, the stabilization of microtubules, distinguished it from other microtubule-binding agents, such as the vinca alkaloids, that act by destabilizing microtubules. In this paper, recent advances in the identification of non-taxane microtubule stabilizing agents for cancer chemotherapy will be discussed with an emphasis on work published in 2000-02.

Cancer Chemopreventive Activities Of Panax Notoginseng And Ginsenoside Rg11

Currently, although many kinds of anti-tumor agents are developed and the medicinal sciences make rapid progress in the treatment of cancer, cancer is the most tragic disease and one of the major cause of death in the world. Therefore, the advancement of cancer chemoprevention is very important as well as the development of cancer treatment. The mechanism of chemical carcinogenesis has been explained by either a two-stage theory or a multi-stage theory, which consist of the initiation, promotion and progression stage.2' In these stages, the promotion stage is long-term and reversible reaction, and the development of the inhibitors on promotion stage (anti-tumor-promoters) have been regarded as the most promissing method for the chemo- prevention of cancer. To search for possible anti-tumor promoters (cancer chemopreventive agents) from natural resources, we carried out an in vitro primary screening of many kind of natural products (triterpenoids3), flavonoids4', euglobals4', plant...

Mmp Inhibitors In Clinical Trials For Cancer

A third study with 29 is focused on patients with the least aggressive cancers. Two of the four trials due to be reported in 2000 involve patients with small-cell lung cancer. These patients have already responded to chemotherapy, so their tumor burden has been reduced to some extent. The other two studies are for patients with glioblastoma and ovarian cancer, both of which are aggressive cancers with high tumor burdens. Prinomastat (AG-3340, 30) is being developed for the treatment of cancer and age-related macular degeneration. In May of 1999, 30 entered Phase III trials for lung and prostate cancers. The recommended dose for these trials was 5 to 25 mg, b.i.d. Following the demonstration of an enhanced efficacy of chemotherapy when supplemented with 30, pilot combination studies and double-blinded, placebo-controlled Phase III trials in 700 patients are in progress for the treatment of non-small cell lung cancer (NSCLC) or advanced hormone-refractory prostate cancer (69). A Phase...

Cancer Epigenetics and Histone Acetylation

Although genetics have played a dominant role in cancer, in recent years the importance of epigenetic regulation of chromatin states through specific modifications to DNA or histones has become widely recognized 62, 284 . Thetermepigeneticisderived from theGreek forupon, epi,and canbeviewed as a secondary level of cellular information, in addition to the genomic DNA sequence, that maybe passed on during cell division. There are three conduits through which epigenetic information has thus far been shown to be conveyed via genomic DNA methylation, histone modification and silencing of genes on parent-of-origin-specific alleles by genomic imprinting. Many of the enzymes responsible for the establishment of specific epigenetic modifications have been identified to date and some have been shown to directly associate with leukaemogenic fusion proteins, such as t(15 17)-associated PML-RARa in APL 164 . An important characteristic of these epigenetic modifications is their potential...

From Cancer Research to Anti Apicomplexa

Since polyamines are known to be essential for cell proliferation and differentiation, numerous approaches have been taken to interfere with their metabolism, not only for tumor therapy but also in a preventive role 6-9 . The inhibition of polyamine biosynthesis, with a resultant depletion of polyamines, was initially proposed as a very promising antiproliferative strategy. Unfortunately, however, attempts to target the synthesis by using enzyme inhibitors and polyamine analogs have not yet proved to be as successful in cancer treatment as anticipated. Nonetheless, the use of these compounds either as preventive agents or in combination with other drugs has provided some benefits in multiple cancer trials. For example, alpha-difluoromethyl-ornithine (DFMO), an irreversible inhibitor of the enzyme ornithine decarboxylase (ODC), which catalyzes the initial step in polyamine biosynthesis, did not provide the expected curative effect in clinical trials, but did show promise as a...

National Cancer Institute Cbc Program

Purpose The NCI Chemical Biology Consortium (CBC) is a developing biotech-like venture designed to assist investigators in the development of novel cancer therapeutics. The program goal is to increase the number of early-stage drug candidates entering the NCI development pipeline by establishing a drug discovery consortium on the scale of a small biotech company. The focus of the group will be on high-risk, underrepresented areas, and in significantly advancing the discovery of novel agents against specific molecular and genetic cancer targets. The program will provide access to cutting-edge tools for iterative drug discovery, optimization, and development, including, when necessary, Phase 0 clinical trials. Project tasks are generally to be completed in collaboration with CBC investigators, NCI's Division of Cancer Treatment and Diagnosis (DCTD), the Center for Cancer Research (CCR) staff, and NCI DTP staff and contractors, rather than through directed investigator grants. The...

Hypoadiponectinemia and Cancers

Low levels of plasma adiponectin are closely correlated with several obesity- and insulin resistance-related cancers. A strong inverse association between plasma adiponectin levels and the risk of both breast cancer and endometrial cancer has recently been reported in two case-control studies (99,100). Importantly, these associations are independent of adiposity, insulin resistance, and other classical risk factors. Another study by Miyoshi et al. has shown that breast cancers arising in women with low adiponectin levels are more likely to show a biologically aggressive phenotype (101). Plasma adiponectin levels in patients with gastric cancer, especially those with upper gastric cancer, were also reported to be much lower than in control subjects (102). Interestingly, in patients with undifferentiated cancer, serum adiponectin showed a negative correlation with pathological findings such as tumor size, depth of invasion, as well as tumor stage. In a large prospective study comprising...

Biomarkers for Increased Risk of Developing Estrogen Initiated Cancer

Many types of markers are being evaluated to estimate risk of developing breast cancer. These include breast density body mass index expression of BRCA1 and or BRCA2 gene cytological changes in breast epithelial cells collected by ductal lavage and levels of estrogens and androgens in serum, breast tissue, or nipple aspirate fluid. Some studies suggest that levels of selected estrogen metabolites, estrogen conjugates, and or depurinating estrogen-DNA adducts in breast ductal fluid, collected either by nipple aspiration or ductal lavage, could prove to be early biomarkers of susceptibility to breast cancer. For example, in the recent study of estrogen metabolites and conjugates in breast tissue, the levels of both 4-OHE1(E2) and the combined 4-catechol estrogen-GSH, Cys, and NAcCys conjugates were significantly higher in women with breast carcinoma than in women without breast cancer (Table 1) (R1). Breast fluid is particularly attractive as a source of biomar-kers because the estrogen...

Section Iv Cancer And Infectious Diseases

Introduction - The incidence of opportunistic fungal infections such as Aspergillus species, Candida spp. (C. albicans and others) and Cryptococcus neoformans has been increasing worldwide despite active research programs devoted to the discovery and development of novel antifungal agents (1,2). Effectively treating opportunistic fungal infections represents a significant threat to the general human condition, especially those with compromised immune systems brought on by chemotherapy treatment for cancer, organ transplants, surgery, and inflictions with HIV AIDS or other immune compromising events (3,4). A second growing concern is the incidence of drug resistance of fungal pathogens to the currently known classes of antifungal agents used in the clinic (5,6). These two factors accentuate the urgency for the ongoing rapid identification of exploitable antifungal targets, to develop safer and more effective therapeutic agents, and to discover new chemical entities (NCE) to fight...

Intracellular Signaling Targets for Cancer Chemosensitization

Introduction - Chemotherapy and radiation exposure are the major options for the treatment of cancer. The application of both of these therapies is limited by severe adverse effects on normal tissues and the frequent development of tumor cell resistance. It is therefore highly desirable to improve the efficacy of these treatments without increasing the toxic side effects and to counteract the resistance mechanisms that can render tumors insensitive to therapy. In this review we will focus on the sensitization of tumors to chemotherapy. Most chemotherapeutic agents are cytotoxic drugs that kill cancer cells by interfering with the cell cycle and inducing cell death, either by disrupting nucleotide precursor synthesis, inducing DNA damage or impairing the function of microtubules. Intrinsic and acquired resistance to such chemotherapy may result from a number of mechanisms that fall into broad classes. These are decreased accumulation of the drug (e.g. by efflux pump overexpression)...

Mammary Adipose Tissue and Breast Cancer

It is known that inflammation can promote tumorigenesis. There is compelling evidence indicating that both normal mammary gland development and breast cancer growth depend, in part, on microenvironment, of which adipose tissue is a key component (ref. 28 and references therein). Interestingly, the mammary gland microenvironment during postlactational involution shares similarities with inflammation, which may be promotional for breast cancer development associated with pregnancy (54). Recently, an elegant study by Celis et al. (28) provided the most extensive proteomic analysis of the mammary adipose secretome in high-risk breast cancer patients. Adipose fibroblasts are another important cellular component of breast cancer microenvironment. These cells, being bona fide steroidogenic cells, are one of the major extragonadal sources of estrogen secretion. Estrogen synthesis is mediated by the enzyme aromatase cytochrome P450 (P450arom), which converts androgens to estrogens (55). In...

Usefulness of Mammography for Breast Cancer Screening

An essential component in determining the efficacy of a screening program is an evaluation of benefits versus risk of harm. For mammography, the major risks to be addressed include radiation-induced breast cancer and the effects of false-positive and false-negative diagnoses. The balancing of potential benefit and harm has been, and continues to be, difficult because of the limited amount of available data. However, it is possible to estimate the recall rate and biopsy-requested rate of mammography screening and to estimate the breast cancer mortality reduction from screening. It is also possible to estimate the average radiation dose received per examination, and the level of risk of radiation-induced breast cancer. When these are considered in the context of the natural incidence of carcinoma of the breast, a benefit risk ratio can be

Epimutations in Cancer

Neoplastic transformation is associated with alterations in DNA methylation, including both global hypomethylation and gene-specific hypermethylation.197-199 Gains of DNA methylation in cancer cells typically reflect hypermethyla-tion of CpG islands in gene promoter regions, which contributes to gene silencing. 1 97 Methylation-dependent gene silencing is a normal mechanism for regulation of gene expression.200 However, in cancer cells methylation-dependent epigenetic gene silencing represents a mutation-independent mechanism for inactivation of tumor suppressor genes or other negative mediators of neoplastic transformation.201 A significant number of cancer-related genes have been identified across all chromosome locations that are subject to methylation-dependent silencing,2 02 and many of these genes contribute to the hallmarks of cancer.203 It is likely that more genes are silenced by hypermethylation than through genetic altera-tions.204 Additionally, some genes that are silenced...

Azacitidine Anticancer [913

Azacitidine is an antineoplastic agent launched last year for the treatment of myelodysplastic syndrome (MDS). MDS is a group of closely related diseases caused by abnormal blood-forming stem cells of the bone marrow. They are characterized by a hyperproliferative bone marrow, the presence of clonal blood cells with impaired morphology and maturation, and peripheral blood cytopenias resulting from ineffective blood cell production. The initial stem cell injury can be from cytotoxic chemotherapy, radiation exposure, chemical exposure, or genetic predisposition. Subsequently a clonal mutation predominates over bone marrow thereby suppressing healthy stem cells. Azacitidine is indicated for the treatment of all five subtypes of MDS, which consist of refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation, and chronic myelomonocytic leukemia. Azacitidine is an analog of cytidine in which...

Pemetrexed Anticancer [7577

Pemetrexed, a pyrrolo 2,3-d pyrimidine-based antifolate that disrupts cell replication by inhibiting multiple folate-dependent metabolic processes, was initially developed and launched in the US for the treatment of malignant pleural mesothelioma in conjunction with cisplatin. Patients who are not candidates for surgery may benefit from this combination therapy. Clinical data demonstrated that the median overall survival time increased to 12.1 months, compared with 9.3 months for patients receiving cisplatin alone. In August of 2004, the FDA also approved pemetrexed as a second-line treatment of non-small-cell lung cancer (NSCLC). While median survival is comparable to the standard second-line treatment docetaxel, the improved toxicity profile (significant reduction in neutropenia) accelerated the approval for NSCLC. Its effectiveness as an anticancer drug is derived from its ability to gain internal cell access via the reduced folate carrier and membrane folate binding protein...

National Cancer Institute Next Program

Purpose The NCI Experimental Therapeutics (NExT) program is designed to assist investigators in bench to bedside translation of novel anticancer therapeutic interventions, synthetic, natural product, or biologic, arising from academic, industrial, or government entities. The program provides the resources for selected discovery tasks, comprehensive pre-clinical IND-enabling tasks, and biomarker development for Phase 0 clinical studies. The tasks are completed by NCI staff and contractors, rather than through direct investigator grants. The program goal is to provide NCI with an integrated pre-clinical pipeline of novel anticancer agents. Website http next.cancer.gov

Erlotinib Anticancer [3942

Erlotinib, launched last year as once daily oral treatment for patients with non-small-cell lung cancer (NSCLC), is an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, and it is the second small-molecule drug to be marketed with this mechanism of action. Both erlotinib and its predecessor, gefitinib, are members of the anilinoquinazoline class of tyrosine kinase inhibitors. They compete with the binding of ATP to the intracellular tyrosine kinase domain of EGFR, thereby inhibiting receptor autophosphorylation and blocking downstream signal transduction. Erlotinib is prepared by the condensation of 3-ethynyl-aniline with which is a key intermediate obtained in five synthetic steps starting from ethyl 3,4-dihydroxybenzoate. In vitro, Erlotinib inhibits purified human EGFR tyrosine kinase with an IC50 of 2 nM and blocks EGFR autophosphorylation in cellular assays with an IC50 of 20 nM. Treatment of human colon cancer cells with erlotinib was associated with...

Cervical Cancer

Approximately 12000 women were newly diagnosed with cervical cancer in the USA in 2003.1 Although cervical cancer remains a leading killer of women worldwide, the incidence in the USA represents a significant decrease, mainly attributable to the widespread implementation of Pap test screening. The Pap smear is designed for detecting pre-invasive disease of the cervix. This allows treatment to be initiated prior to the development of cancer.2 Human papillomavirus (HPV) is a sexually transmitted virus associated with cervical dysplasia and invasive cancer. Low-risk HPV types, such as 6 and 11, are associated with cervical intraepithelial neoplasia (CIN) I and condyloma. High-risk types of HPV, such as types 16, 18, 31, 33 and 35, are observed in association with high-grade dysplasia or cervical cancer. HPV DNA can be detected in close to 100 of patients with invasive cervical cancer. Although the prevalence of HPV in some populations approaches 30-90 , only a small number of these women...

Vaginal Cancer

Primary vaginal cancer is a rare malignancy, representing approximately 2 of gynaecological malignancies and only approximately 0.1-0.2 of all cancers.1 The vast majority (85 ) of vaginal cancers are of squamous origin however, adenocarcinomas, clear cell carcinomas, melanomas and sarcomas are infrequently identified. Although secondary vaginal carcinomas are more common than primary tumours, the keen pathologist can distinguish between the two using conventional standards. Specifically, a primary vaginal cancer should be diagnosed only when the cervix is uninvolved with an obvious focus of tumour origin in the vagina. When an apparent malignancy is found in the vagina and these conditions are not met, secondary vaginal cancer should be considered. Secondary vaginal cancer may represent an extension from a cervical cancer or metastatic disease from a uterine, ovarian, vulvar, bladder or colon primary tumour. Many authors deem the stage of disease at the time of diagnosis as the most...

Lung Cancer

Changes in the structure of some of the many types of cells that make up the lungs may begin almost immediately upon exposure to carcinogens (cancer-causing substances). Some of the thousands of chemicals contained in tobacco smoke both inhaled directly and released into the air through secondhand smoke are known respiratory carcinogens. Substances such as radon, asbestos, arsenic, uranium, and certain petroleum products also can cause lung cancer. malignant, however, it can invade and destroy surrounding tissue and may spread to other parts of the body through the bloodstream, causing new tumors (called metastases) to form in other tissues. And because all blood flows through the lungs, cancer that begins elsewhere in the body may spread to the lungs. A tumor in one of the bronchi can irritate the lining of the airway and cause a persistent cough, which may cause the tumor to bleed. As it grows, the tumor may block the airway, resulting in repeated bouts of pneumonia or other...

Cancer

Previous epidemiological studies have pointed to an association between low serum cholesterol levels and the incidence of gastro-intestinal cancers, in particular colorectal cancer 129 . This topic is still controversial 130,131 . However, this data taken together with the increasing evidence that statins can act as immunomodulators, in both animal models and in vitro, and the role of statins in reversing hypoxic inhibition of eNOS, thereby promoting increased local blood flow through eNOS activity, have raised concerns over the long term use of statins in terms of immune surveillance for tumours. However, large scale prolonged clinical trials have given no evidence for an association of statin use with cancer 132 .

Endometrial Cancer

Endometrial cancer (cancer of the uterine lining) was the first cancer to be recognized as being obesity-related. There is convincing and consistent evidence from both case-control and cohort studies that overweight and obesity are associated strongly with endometrial cancer (18,33). A linear increase in the risk of endometrial cancer with increasing weight or BMI has been observed in most studies (3,18,34-36). The increase in risk generally ranges from 2- to 3.5-fold in overweight and or obese women (Table 3), and might be somewhat higher in studies of mortality than incidence (3,18,37). The probable mechanism for the increase in risk of endometrial cancer associated with obesity in postmenopausal women is the obesity-related increase in circulating estrogens (38). In premenopausal women, endometrial cancer risk is also increased among women with polycystic ovary syndrome, which is characterized by chronic hyperinsulinemia and progesterone deficiency (39). Thus, in both pre- and...

Colorectal Cancer

Obesity has also been consistently associated with higher risk of colorectal cancer in men (relative risks of approx 1.5 to 2.0) and women (relative risks of approx 1.2 to 1.5) in both case-control and cohort studies (Table 3) (18,34,35,94,95). In studies that were able to examine the colon and rectum separately, relative risks have been generally higher for the colon (18,36,96). Similar relationships are seen for colon adenomas, with stronger associations observed between obesity and advanced adenomas (97-100). A gender difference, in which obese men are more likely to develop colorectal cancer than obese women, has been observed consistently across studies and populations. The reasons for this gender difference are speculative. One hypothesis is that central adiposity, which occurs more frequently in men, is a stronger predictor of colon cancer risk than peripheral adiposity or general overweight. Support for the role of central obesity in colo-rectal cancer comes from studies...

Kidney Cancer

The risk of kidney cancer (specifically, renal cell cancer) is 1.5- to 3-fold higher in overweight and obese persons than in normal weight men and women in study populations worldwide (Table 3) most studies have found a dose-response relationship with increasing weight or BMI (18,35,96,129-133). In several studies, the increase in risk with increasing BMI was greater in women than in men (3,134-141), although at present this finding remains unexplained and was not confirmed in a review of published studies (129), nor in a recent prospective cohort study (35). Importantly, the obesity-associated risk of renal cell cancer appears to be independent of blood pressure, indicating that hypertension and obesity might influence renal cell cancer through different mechanisms (142). The hypothesis that chronic hyperinsulinemia contributes to the association of BMI and renal cell cancer is supported indirectly by the increased risk of kidney cancer seen in diabetics (143).

Gallbladder Cancer

There have been a limited number of studies of gallbladder cancer and obesity most have been relatively small, as gallbladder cancer is quite rare, especially in men. However, these few studies have consistently found elevated risks of about twofold (Table 3) (3,37,96,132,155-158). One study found a greater than fourfold increase in risk for the highest category of BMI (> 30) in a Japanese cohort, but only among women (36). Obesity is thought to operate indirectly to increase the risk of gallbladder cancer by increasing the risk of gallstones, which in turn, causes chronic inflammation and increased risk of biliary tract cancer (134).

Liver Cancer

Seven studies that have examined obesity and liver cancer or hepatocellular carcinoma (HCC) found excess relative risk in both men and women in the range of 1.5 to 4.0 (3,34,95,96,132,155,158) however, two studies did not find any suggestion of an increased risk (36,131). Taken together, these studies suggest that obesity increases the risk of liver cancer, but the magnitude of the observed relative risk from existing studies is not consistent.

Pancreatic Cancer

Several recent studies suggest that high body mass is associated with increased risk for pancreatic cancer in men and women, with relative risk estimates for obesity generally in the range of 1.5 to 2.0 (Table 3) (3,34,131,155,158,161-166). However, other studies found smaller positive associations (36,132,167) or, in some cases, no association (35,95,96,168,169). Further research is needed to refine the magnitude of the risk in both men and women and to explain the inconsistency in current estimates of risk. Many of these studies are based on small numbers of cases, and retrospective studies of adiposity are hampered by weight loss that accompanies pancreatic cancer and that often begins prior to diagnosis. In addition, smoking is an important potential confounder of the relationship between adiposity and pancreatic cancer, and the smoking habits of the various study populations and differential adequacy of control for smoking may partly explain differences across studies. It is...

Prostate Cancer

There are many studies that do not support an association between body mass and incident prostate cancer (18,34-36,173), although four large recent studies found a small but statistically significant increased risk of prostate cancer among obese men (131,132,174) or a significant trend toward increasing risk with increasing BMI (96). In addition, there is accumulating evidence that obesity is associated with an increase in risk of advanced prostate cancer or death from prostate cancer (175-181). Recent studies consistently indicate that obese men with prostate cancer are more likely to have aggressive disease that recurs after radical prostatectomy than nonobese men (182-184). As with breast cancer, nonbiological issues of screening, detection, and treatment are important to the evaluation of the impact of adiposity on prostate cancer prognosis. It can be harder to perform a digital rectal examination in obese men because of their general adiposity in combination with larger prostate...

Ovarian Cancer

Ovarian cancer constitutes nearly 4 of all cancers among women and is the leading cause of death from gynaecological malignancies in the Western world. It was estimated that 24 400 new cases of ovarian cancer would be diagnosed and 14 300 deaths would occur from ovarian cancer in the USA in 2003. The overall incidence rate in the USA is 17.1 per 100 000 women and has been fairly stable over time.1 The age-specific incidence of ovarian cancer increases with age and peaks in the eighth decade. The median age of diagnosis is 63 years. Tumours of the ovary form a heterogeneous group of neoplasms. The surface epithelium, stroma and germ cells each cause an array of histogenetically distinctive tumours that can occur in pure or combined forms.2 Malignant epithelial tumours account for approximately 85 of ovarian cancers. Age at diagnosis, race, stage of the disease, tumour grade and histological type of tumour have all been shown to have a significant impact on prognosis. An improved...

Oral Cancer

Oral cancer is one of the most debilitating and disfiguring types of cancer. Tumors affecting the lip, mouth, tongue, and soft palate (the part of the throat at the back of the mouth) can interfere with swallowing and speech. If the cancer spreads to other parts of the body, it can cause disability and even death. But if oral cancer is detected and treated early, it has a very high cure rate. More important is the fact that oral cancer is highly preventable. Tobacco use is the number one cause of oral cancer. A smoker's risk of oral cancer is two to four times higher than that of nonsmokers. In fact, people who are most at risk of developing oral cancer are men over age 40 who smoke cigarettes, cigars, or a pipe, or who use smokeless tobacco (chewing tobacco or snuff). Smokeless tobacco is particularly dangerous because it contains 100 times the amount of cancer-causing compounds found in other forms of tobacco. This fact is especially disturbing because the use of smokeless tobacco...

10 Ways To Fight Off Cancer

10 Ways To Fight Off Cancer

Learning About 10 Ways Fight Off Cancer Can Have Amazing Benefits For Your Life The Best Tips On How To Keep This Killer At Bay Discovering that you or a loved one has cancer can be utterly terrifying. All the same, once you comprehend the causes of cancer and learn how to reverse those causes, you or your loved one may have more than a fighting chance of beating out cancer.

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