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Query: UNIPROT:Q86TM3 (cage)
 29,987 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

During the past fifteen years strong evidence has accumulated that particular types of human papilloma viruses are involved in the aetiology of cervical cancer. Early reports suggested that women with cytological signs of papilloma virus infection have a significantly higher risk to develop cervical cancer. Recent studies with sensitive detection methods for viral nucleic acids, however, demonstrated that latent papilloma virus infections are widespread and that only a minor part of infected people will suffer from epithelial lesions that may progress to invasive cancer. The infection per se is apparently not sufficient to induce the malignant phenotype in genital keratinocytes. Detailed molecular analysis of cervical cancer cells revealed that the DNA of the cancer associated papilloma viruses is usually integrated into the cellular genome of the carcinoma cells. Only two viral genes (E6 and E7) are always preserved in a functional active state. The expression of these two genes is deregulated since physiological control mechanisms for viral gene expression are eliminated by the integration process. Artificial introduction of the E6-E7 genes into genital keratinocytes leads to unlimited growth of these cells in tissue culture but does not convert them into the malignant state. Keratinocytes that express the E6-E7 genes resemble in some aspects cells found in premalignant lesions, e.g. the cervical intraepithelial neoplasia (CIN). Thus, the deregulated expression of the papilloma virus E6-E7 genes appears not to be sufficient to evoke cancer. Additional not yet characterized factors must cooperate with the viral E6-E7 genes to transform keratinocytes into the full malignant phenotype.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[The role of papillomaviruses in the etiology of cervix cancer]. 216 60

Cumulative evidence strongly implicates human papillomavirus (HPV) in the genesis of squamous neoplasia of the lower female genital tract, including the vulva. The association of HPV with neoplasms at that site includes the relationship of specific HPV types with neoplasms and evidence that those HPV DNA types can transform epithelial cells in vitro. The capacity for in vitro transformation has been isolated to specific regions of the HPV genome. That may be unique in cancer-associated viruses. Nevertheless, epidemiologic evidence points to additional factors, including immunologic, habitual and environmental, that may play an important role in the development of lower genital tract carcinomas. In particular, the marked differences in mean age and other variables between women with vulvar precancers and invasive cancer suggest that the evolution of invasive cancer involves more than HPV infection alone. Hence, the prevention of invasive vulvar cancer in older age groups will require an understanding of the unique host factors that render a small group of women susceptible to the disease in the face of an epidemic of HPV infection in the population at large.
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PMID:Papillomavirus and vulvovaginal neoplasia. 255 10

Focal apocrine metaplasia was studied in 293 whole human breasts by a subgross sampling technique with histologic confirmation. There were 186 breasts obtained from random autopsies. Another 107 breasts were obtained that were cancer-associated; these breasts either contained an invasive cancer or were situated contralateral to a cancer-containing breast. The observations support a lobular origin for most if not all apocrine metaplasia and demonstrate some correlation between the presence of apocrine metaplasia and coincident invasive breast cancer on either the contralateral or ipsilateral side. When extensive, apocrine metaplasia appears to be a useful phenotypic marker for tissue at a modestly increased risk for breast cancer. There were no breast carcinomas of the apocrine type in this series, supporting the belief that apocrine metaplastic epithelium has little intrinsic malignant potential. Finally, the data support the hypothesis that most breast cysts arise from apocrine metaplastic lobules.
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PMID:Apocrine cystic metaplasia: subgross pathology and prevalence in cancer-associated versus random autopsy breasts. 355 40

A detailed retrospective analysis was undertaken of the effect of perioperative blood transfusion on long-term survival of 113 patients with Dukes' Stages A, B and C1 cancer of the colon and 383 patients with invasive cancer of the breast who were treated in our institution between 1973 and 1978 and followed for 5 to 10 years. In the patients with colon cancer, a significant adverse effect of transfusion on long-term survival was seen. In this group there was a cumulative 5-year overall survival of 48% for the transfused and 74% for the nontransfused patients (P = 0.007, log-rank test). Perioperative blood transfusion was associated with a relative risk of 3.42 for all deaths (P = 0.005) and 4.25 for death due to cancer (P = 0.03), after adjustment for other important variables such as age, sex, stage, location of tumor, surgical procedure, and preoperative hemoglobin level. In contrast, in our study group of patients with breast cancers, who all underwent a modified radical mastectomy, no effect of blood transfusion on long-term survival was seen. Multivariate analysis adjusting for size of tumor, number of positive regional lymph nodes, menopausal status, estrogen receptor status and the addition or absence of chemotherapy, did not show any increased risk in all deaths or death due to cancer associated with blood transfusion. Although no definite explanation is available, our data show that there seems to be a difference in the relationship between perioperative blood transfusion and survival for colon and breast cancer patients.
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PMID:Perioperative blood transfusion and cancer prognosis. Different effects of blood transfusion on prognosis of colon and breast cancer patients. 380 42

Epidemiologic evidence on the relation between nutrition and cervical cancer is reviewed. Cervical cancer is the leading cancer among women in many developing countries, and remains a major public health problem worldwide. This review of nutritional research on cervical neoplasia encompasses the range of epithelial abnormalities from early preneoplastic lesions to invasive cancer. Identified risk factors for cervical neoplasia suggest a multifactorial etiology with several cancer-associated human papillomaviruses (HPV) as the central cause. Studies of nutritional predictors of cervical neoplasia to date, however, have been limited by inadequate HPV measures, which compromise the interpretations of findings. Current research using accurate measures of HPV will be most revealing. Nonetheless, agreement in findings from previous studies suggest a role for nutritional factors in some or all stages of cervical neoplasia. Low vitamin C and carotenoid status are associated fairly consistently with both cervical cancer and precursors, whereas results for vitamin E status are less consistent. The effect of folate status may be restricted to early preneoplastic cervical lesions and not to more advanced disease. Current research is addressing nutritional influences on HPV infection and persistence and on progression of cervical disease. Limitations and recommendations for future research directions are discussed in light of methodologic issues related to nutritional and HPV research.
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PMID:Nutrition and cervical neoplasia. 885 Apr 40

Human papillomavirus (HPV) DNA has been detected in the great majority of cancers of the uterine cervix and anus, whereas the association of HPV DNA with cancer at other anogenital sites has produced less consistent results. This study was designed to compare HPV exposure among anogenital cancer cases and matched controls. Cases (1782) of anogenital cancer diagnosed in the Seattle area from 1978 to 1998 were identified and interviewed. Their responses were compared with those of 2383 age- and sex-matched controls. Blood was drawn at interview from both cases and controls and tested for antibodies to HPV-16 and HPV-18. Tissue blocks were tested for HPV DNA for 649 cases. Serum antibodies to HPV-16 were associated with in situ and invasive cancer at all sites among men and women with the exception of in situ penile cancer. Anti-HPV-18 antibodies were associated with cancers at all sites among women. The increased risk of cancer associated with HPV-16 seropositivity ranged from odds ratio = 1.8 (95% confidence interval, 1.4-2.5) for adenocarcinoma of the cervix to odds ratio = 5.9 (95% confidence interval, 3.4-10.3) for anal cancer in men. Associations between seroprevalence and cancers were stronger when analyses were restricted to HPV-16- or HPV-18 DNA-positive cases. HPV DNA was detected in >80% of cancers from all sites tested. HPV-16 DNA was the type most frequently detected at all sites (range, 40.9-82.2%). HPV-18 DNA was detected in 44.7% of adenocarcinomas of the cervix but detected much less often (2.6-18.1%) at other sites. These findings support an important role for HPV infection in anogenital cancer at all sites. Differences in the proportion of seropositives among HPV-16 DNA-positive cases by site suggest either that the immune response varies by site or that cancer development may lead to changes in antibody responses in a site-specific fashion.
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PMID:Human papillomavirus 16 and 18 L1 serology compared across anogenital cancer sites. 1128 Jul 49

A multistep model of carcinogenesis has recently been proposed for pancreatic ductal adenocarcinomas. In this model, noninvasive precursor lesions in the pancreatic ductules accumulate genetic alterations in cancer-associated genes eventually leading to the development of an invasive cancer. The nomenclature for these precursor lesions has been standardized as pancreatic intraepithelial neoplasia or PanIN. Despite the substantial advances made in understanding the biology of invasive pancreatic adenocarcinomas, little is known about the initiating genetic events in the pancreatic ductal epithelium that facilitates its progression to cancer. Telomeres are distinctive structures at the ends of chromosomes that protect against chromosomal breakage-fusion-bridge cycles in dividing cells. Critically shortened telomeres can cause chromosomal instability, a sine qua non of most human epithelial cancers. Although evidence for telomeric dysfunction has been demonstrated in invasive pancreatic cancer, the onset of this phenomenon has not been elucidated in the context of noninvasive precursor lesions. We used a recently described in situ hybridization technique in archival samples (Meeker AK, Gage WR, Hicks JL, Simon I, Coffman JR, Platz EA, March GE, De Marzo AM: Telomere length assessment in human archival tissues: combined telomere fluorescence in situ hybridization and immunostaining. American Journal of Pathology 2002, 160:1259-1268) for assessment of telomere length in tissue microarrays containing a variety of noninvasive pancreatic ductal lesions. These included 82 PanIN lesions of all histological grades (24 PanIN-1A, 23 PanIN-1B, 24 PanIN-2, and 11 PanIN-3) that were selected from pancreatectomy specimens for either adenocarcinoma or chronic pancreatitis. Telomere fluorescence intensities in PanIN lesions were compared with adjacent normal pancreatic ductal epithelium and acini (62 of 82 lesions, 76%), or with stromal fibroblasts and islets of Langerhans (20 of 82 lesions, 24%). Telomere signals were strikingly reduced in 79 (96%) of 82 PanINs compared to adjacent normal structures. Notably, even PanIN-1A, the earliest putative precursor lesion, demonstrated a dramatic reduction of telomere fluorescence intensity in 21 (91%) of 23 foci examined. In chronic pancreatitis, reduction of telomere signal was observed in all PanIN lesions, whereas atrophic and inflammatory ductal lesions retained normal telomere length. Telomere fluorescence intensity in PanIN lesions did not correlate with proliferation measured by quantitative Ki-67-labeling index or topoisomerase IIalpha expression. Thus, telomere shortening is by far the most common early genetic abnormality recognized to date in the progression model of pancreatic adenocarcinomas. Telomeres may be an essential gatekeeper for maintaining chromosomal integrity, and thus, normal cellular physiology in pancreatic ductal epithelium. A critical shortening of telomere length in PanINs may predispose these noninvasive ductal lesions to accumulate progressive chromosomal abnormalities and to develop toward the stage of invasive carcinoma.
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PMID:Telomere shortening is nearly universal in pancreatic intraepithelial neoplasia. 1241 2

Solid tumors co-opt the body's endogenous extracellular proteolytic machinery for their invasion and metastasis. This is supported by a large number of independent observations ranging from histochemical and prognostic studies of cancer patient material to animal experiments. There are several extracellular proteolytic systems that are relevant in the context of cancer, but the plasminogen activation (PA) system and the matrix metalloproteases (MMPs) remain the most thoroughly investigated. Localization studies by immunohistochemistry and in situ mRNA hybridization in tumors of common human cancers have repeatedly identified members of the PA and MMP systems in stromal cells. The cancer cells, of epithelial origin, contribute PA and MMP components in some cases, but their contribution fades in comparison with the overwhelming expression of proteolytic components by fibroblasts, macrophages, endothelial cells, and other stromal cells. Ideal animal models of human cancers should recapitulate this fundamental proteolytic aspect of tumor biology. However, in the transplantable tumor models where PA or MMP components have been studied at the cellular level in vivo, this is most often not the case. Transgenic cancer models may provide a closer parallel to the human situation, in that PA and MMP components are synthesized by the tumor stroma. The pivotal role of stromal cells has been confirmed experimentally in mouse models in which the expression pattern of proteolytic components is strongly reminiscent of human tumors. In these models it is possible to reconstitute the wild-type tumor characteristics of proteolytically deficient tumor-bearing mice by transplantation with wild-type fibroblasts or hemapoietic cells. These studies collectively show that cancer-associated proteolysis is a collaborative effort of malignant cancer cells and various stromal cells--a collaboration in which stromal cells contribute the majority of the active proteolytic components that are necessary for the invasive behavior of the tumors. This cellular division of labor positions the stromal cells as prime targets for future research and possibly therapy. Vascular endothelial cells are already the focus of intense therapeutically relevant research, but tumor-associated fibroblasts, macrophages, neutrophils, lymphendothelial cells, etc. provide additional largely unexplored territory in the ongoing search for efficient countermeasures against invasive cancer.
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PMID:Stromal cell involvement in cancer. 1279 Mar 19

Pancreatic cancer is an almost universally lethal disease. Research over the last two decades has shown that pancreatic cancer is fundamentally a genetic disease, caused by inherited germline and acquired somatic mutations in cancer-associated genes. Multiple alterations in genes that are important in pancreatic cancer progression have been identified, including tumor suppressor genes, oncogenes, and genome maintenance genes. Furthermore, the identification of noninvasive precursor lesions of pancreatic adenocarcinoma has led to the formulation of a multi-step progression model of pancreatic cancer and the subsequent identification of early and late genetic alterations culminating in invasive cancer. In addition, an increased understanding of the molecular basis of the disease has facilitated the identification of new drug targets enabling rational drug design. The elucidation of genetic alterations in combination with the development of high-throughput sensitive techniques should lead to the discovery of effective biomarkers for early detection of this malignancy. This review focuses mainly on the current knowledge about the molecular insights of the pathogenesis of pancreatic ductal adenocarcinoma.
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PMID:Pancreatic carcinogenesis. 1838 97

According to recently published data, the epithelial-mesenchymal transition--a process important for embryonic development, may be involved in many pathological processes such as wound healing, tissue fibrosis or cancer progression. The EMT process in cell is driven by growth factors (EGF, PDGF, HGF) or other signaling proteins such as TGF-beta, sonic hedgehog (Shh), Wnt/beta-catenin and extracellular matrix (ECM) components that may stimulate cellular growth and migration. During cancer progression, the EMT process is necessary to the conversion of benign tumor to aggressive and highly invasive cancer. This is due to complex changes in cancer cells and their microenvironment that lead to dissolution of intracellular junctions and their detachment from basolateral membrane, and changes in the interactions between cancer cells and ECM. The loss of adhesion is accompanied by molecular and morphologic changes in cancer cells that are essential for the phenotypic change from epithelial to mesenchymal one, and the acquirement of higher migration and invasion potential. During the colonization of distant sites, a reverse process mesenchymal-epithelial transition (MET) takes place and metastatic cancer cells again acquire the epithelial phenotype. The EMT in cancer progression is not only specific for cancer cells. It has been suggested that also cells within tumor microenvironment e.g. cancer associated fibroblasts (CAF) are generated in part from normal epithelial cells in EMT process. The understanding of the role of EMT and MET processes in cancer progression and their relationship with cancer stem cells, cancer associated fibroblasts and other stroma cells might lead to the discovery of new, targeted cancer therapies.
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PMID:[Epithelial-mesenchymal transition in cancer progression]. 1982 67


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