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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The traditional prognostic factors, including stage of disease and tumour grade, have shown a limited prognostic significance and an inability to predict clinical response to specific treatment in patients with laryngeal squamous-cell carcinoma. More recent data suggest that cell kinetics indices, DNA-ploidy, lysosomal cysteine proteinase expression and genetic changes of both tumour suppressor genes and protooncogenes may be considered as reliable and reproducible indicators of biological aggressiveness in these patients. Moreover, the frequency of different genetic alterations suggests that several pathways are involved in the genesis of these neoplasias and, in particular, it is very probable that p-53 expression and PCNA indices (increased in normal mucosa and preinvasive lesions) may constitute more important biomarkers for the early steps of laryngeal carcinogenesis.
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PMID:Biological characterization of laryngeal squamous-cell carcinoma. 869 53

Pancreaticobiliary maljunction is associated frequently with gall-bladder carcinoma. Although increased turnover of the gall-bladder epithelium in patients with pancreaticobiliary maljunction is thought to predispose to carcinogenesis, there is little data to confirm this hypothesis. In addition, no previously published study has addressed the process underlying cell proliferation. In this study, cell kinetics were first evaluated using two methods, proliferating cell nuclear antigen (PCNA) immunohistochemical staining and argyrophilic nucleolar organizer region (AgNOR) staining. Second, immunohistochemistry was used to investigate the expression of transforming growth factor-alpha (TGF alpha), a potential regulator of cell proliferation in the gall-bladder. The gall-bladders of 11 patients with pancreaticobiliary maljunction were studied, and 11 gall-bladders removed from patients during other surgery were used as controls. The number of PCNA-positive cells and the number of AgNOR per nucleus were significantly greater in the gall-bladders of patients with pancreaticobiliary maljunction than in the control gall-bladders. The expression of TGF alpha was also significantly greater in the gallbladders of patients with pancreaticobiliary maljunction than in the control gall-bladders. In conclusion, these results suggest that the increased TGF alpha expression induced by pancreaticobiliary maljunction promotes proliferation of the gall-bladder epithelium, which may lead to carcinogenesis.
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PMID:Increased cell proliferation and transforming growth factor-alpha (TGF alpha) in the gall-bladder epithelium of patients with pancreaticobiliary maljunction. 872 48

Histopathological and immunohistochemical studies during carcinogenesis in rat submandibular glands (SMGs) using a carcinogen (9,10-dimethyl-1,2-benzanthracene: DMBA) were evaluated. For carcinogenesis, the carcinogen-containing sponge was surgically inserted into the gland. Histopathological features during carcinogenesis were as follows; dilatation of ductal segments, the presence of duct-like structures and cystic lesion around the sponge were observed within 3 weeks of the experiment, squamous metaplasia in duct-like structures and lining epithelium of the cystic structures around the sponge were observed at 4-6 weeks of the experiment, and finally well differentiated squamous cell carcinomas (SCCs) were observed after 8 weeks of the experiment. The immunoreactivity of K8.12 keration (K8.12), S-100 protein (S-100), epidermal growth factor (EGF), laminin, and proliferating cell nuclear antigen (PCNA) were evaluated. In the normal SMG, EGF was confined to the granular cells and S-100 to the pillar cells of granular convoluted tubules (GCTs). K8.12 was found in striated (SD) and excretory duct (ED) cells and laminin showed linear staining of the basement membrane around the ducts, acini and blood vessels. PCNA-positive nuclei were rarely observed in the normal glandular parenchyma. During carcinogenesis, during the first stage, EGF in granular cells and S-100 in pillar cells of GCT segments disappeared, and cytokeration K8.12 was observed in duct-like structures and cystic epithelium around the DMBA sponge. PCNA-positive nuclei in the first stage were mainly confined to basal cells of morphologically altered ducts. During the second stage, squamous metaplastic cells showed an intense K8.12 reaction. During the third stage, the well differentiated SCC showed strong reaction for K8.12, and the linear staining for laminin staining had disappeared at the invading fronts. The PCNA index was nearly 40% in the tumour cell component. The stem cells or the progenitor cells during experimental carcinoma were most likely to be the ductal basal cells, and carcinogenesis was initiated with an increase of proliferating activity in small cell clusters surrounding a necrotic area, basal cells of dilated excretory ducts and duct-like structures. Thus, all ductal segments undergoing squamous metaplasia may participate in the genesis of neoplasia during experimental carcinogenesis.
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PMID:Growth pattern of experimental squamous cell carcinoma in rat submandibular glands--an immunohistochemical evaluation. 873 71

Well-designed and conducted Phase II clinical trials are very important to cancer chemoprevention drug development. Three critical aspects govern the design and conduct of these trials--well-characterized agents, suitable cohorts, and reliable biomarkers for measuring efficacy that can serve as surrogate endpoints for cancer incidence. Requirements for the agent are experimental or epidemiological data showing chemopreventive efficacy, safety on chronic administration, and a mechanistic rationale for the chemopreventive activity observed. Agents that meet these criteria for chemoprevention of cervical cancer include antiproliferative drugs (e.g., 2-difluoromethylornithine), retinoids, folic acid, antioxidant vitamins and other agents that prevent cellular oxidative damage. Because of the significant cervical cancer risk associated with human papilloma virus (HPV) infection, agents that interfere with the activity of HPV products may also prove to be effective chemopreventives. In endometrium, unopposed estrogen exposure has been associated with cancer incidence. Thus, pure antiestrogens and progestins may be chemopreventive in this tissue. Ovarian cancer risk is correlated to ovulation frequency; therefore, oral contraceptives are potentially chemopreventive in the ovary. Recent clinical observations also suggest that retinoids, particularly all-trans-N-4-hydroxyphenylretinamide, may be chemopreventive in this tissue. The cohort should be suitable for measuring the chemopreventive activity of the agent and the intermediate biomarkers chosen. In the cervix, patients with cervical intraepithelial neoplasia (CIN) and in endometrium, patients with atypical hyperplasia, fit these criteria. Defining a cohort for a Phase II trial in the ovary is more difficult. This tissue is less accessible for biopsy; consequently, the presence of precancerous lesions is more difficult to confirm. The criteria for biomarkers are that they fit expected biological mechanisms (i.e., differential expression in normal and high-risk tissue, on or closely linked to the causal pathway for the cancer, modulated by chemopreventive agents, and short latency compared with cancer), may be assayed reliably and quantitatively, measured easily, and correlate to decrease cancer incidence. They must occur in sufficient incidence to allow their biological and statistical evaluation relevant to cancer. Since carcinogenesis is a multipath process, single biomarkers are difficult to validate as surrogate endpoints, perhaps appearing on only one or a few of the many possible causal pathways. Panels of biomarkers, particularly those representing the range of carcinogenesis pathways, may prove more useful as surrogate endpoints. It is important to avoid solely on biomarkers that do not describe cancer but represent isolated events that may or may not be on the causal pathway or otherwise associated with carcinogenesis. These include markers of normal cellular processes that may be increased or expressed during carcinogenesis. Chemoprevention trials should be designed to evaluate fully the two or three biomarkers that appear to be the best models of the cancer. Additional biomarkers should be considered only if they can be analyzed efficiently and the sample size allows more important biomarkers to be evaluated completely. Two types of biomarkers that stand out regarding their high correlation to cancer and their ability to be quantified are measures of intraepithelial neoplasia and indicators of cellular proliferation. Measurements made by computer-assisted image analysis that are potentially useful as surrogate endpoint biomarkers include nuclear polymorphism comprising nuclear size, shape (roundness), and texture (DNA distribution patterns); nucleolar size and number of nucleoli/nuclei; DNA ploidy, and proliferation biomarkers such as S-phase fraction and PCNA...
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PMID:Strategies for phase II cancer chemoprevention trials: cervix, endometrium, and ovary. 874 72

Tenascin (TN) is an extracellular matrix glycoprotein that seems to be involved in embryogenesis, carcinogenesis and wound healing. In order to clarify the biological significance of TN in the human endometrium, we investigated its expression in the normal as well as in the hyperplastic and neoplastic human endometrium, using immunohistochemistry. We also investigated the coexistence of TN with proliferating cell nuclear antigen (PCNA), a marker of cell proliferation, in endometrial carcinoma to further assess the involvement of TN in regulating cell proliferation. TN expression was observed in the stroma surrounding the endometrial gland in the proliferative phase, whereas it could not be found in the secretory phase. The localization of TN and PCNA coincided frequently, as the stromal portion where the expression of TN was observed always showed positive for PCNA. These results suggest that TN is involved in cell proliferation and carcinogenesis in the human endometrium.
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PMID:Immunohistological localization of tenascin in the human endometrium. 879 95

Sarcophytol A (SaA), a cembrane-type diterpene, inhibits pancreatic carcinogenesis induced by N-nitrosobis(2-oxypropyl)amine (BOP) in hamsters. The experimental groups received two injections of BOP at 70 mg/kg dose, followed 2 weeks later by a 20 mg/kg dose injection, and were fed a basal diet or 0.01 and 0.05% SaA diets starting 1 week after the second injection of BOP. Control groups were injected with normal saline and fed the basal diet or the 0.05% SaA diet. All animals were killed 30 weeks after the start of the experiments. Seventeen BOP-treated hamsters fed the basal diet developed pancreatic tumors (77.3%) while only 12 of 21 hamsters fed the 0.01% SaA diet (57.1%) and 12 of 23 hamsters fed the 0.05% SaA diet (52.2%) developed pancreatic tumors. Pancreatic lesions included ductal hyperplasia, atypical ductal hyperplasia, and carcinoma in situ. Microscopic invasive carcinoma induced by BOP and the incidence of larger pancreatic tumors in hamsters were significantly higher in hamsters fed the basal diet than in hamsters fed the SaA diet (p < 0.05). The proliferating cell nuclear antigen (PCNA) labeling index of pancreatic carcinoma in BOP-treated hamsters fed the basal diet was 41.2 +/- 13.4%, whereas BOP-treated hamsters fed 0.01 and 0.05% SaA diets yielded PCNA indexes of 26.8 +/- 8.3 and 28.4 +/- 7.0%, respectively. k-ras mutation was detected in 40% of cancers in both groups. No pancreatic tumors developed in saline-treated groups, and no differences in body weights or histological findings in their organs, including the pancreas, were observed in either group. These findings suggest that SaA not only inhibits BOP-induced pancreatic carcinogenesis in hamsters, but also provides antipromotion and antiprogression effects on these tumors, even when SaA commences 1 week after the initiation of pancreatic carcinogenesis.
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PMID:Inhibitory effect of sarcophytol A on pancreatic carcinogenesis after initiation by N-nitrosobis(2-oxypropyl)amine in Syrian hamsters. 882 83

Heat shock proteins (hsps) are thought to play important roles in the cell cycle and various processes of carcinogenesis. Therefore, we evaluated the expression of hsps, mainly hsp90 and hsp70, in human breast cancer tissues. Hsp90alpha mRNA was expressed at much higher levels in the cancerous tissue than in the non-cancerous tissue. In addition, a close correlation between hsp90alpha mRNA expression and the proliferating-cell-nuclear-antigen labeling index (PCNA LI) was observed for the cancerous tissue. These findings suggest that increased expression of the hsp90alpha isoform may play a role in cell proliferation. On the other hand, hsp90beta mRNA expression was significantly higher in poorly differentiated carcinomas than in well differentiated carcinomas of the breast. The intracellular localization of hsp70 was consistent with that of ubiquitin. In specimens showing hsp70 in the nucleus, the PCNA LI was significantly high. Hsc73 mRNA, a member of the hsp70 family, was also expressed at higher levels in cancerous tissues associated with a high PCNA LI than in non-cancerous tissues. These results suggest that hsp90alpha may play a role in cancer cell proliferation and that hsp90beta may contribute to cell differentiation and structural constitution. In addition, hsp70, especially hsc73, is related to ubiquitin and seems to be a marker for cancer proliferation.
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PMID:Expression and roles of heat shock proteins in human breast cancer. 887 52

Histological type, malignancy grade, and tumor stage are among the most important parameters predicting outcome in cancer patients. Making use of immunocytochemistry as well as polymerase chain reaction-based techniques the demonstration of micrometastatic tumor spread, for example, into bone marrow, lymph nodes, and peritoneal cavity, is a new staging parameter of prognostic significance. In contrast, the prognostic value of different proliferation markers such as Ki67 (Mib 1), PCNA, and AgNOR has not yet been unequivocally established. A series of genetic change has been described in the development of cancer. In general, these changes seem to be of predictive value within defined tumor stages and it might be helpful to determine several genetic lesions within one tumor. Very recently a new mechanism of carcinogenesis closely related to the hereditary nonpolyposis cancer syndrome (HNPCC) was detected. Due to mutations in mismatch repair genes (hMSH 2, hMLH1, hPMS1,2) instabilities in simple repetitive genomic sequences occur, which are the genetic hallmark of most HNPCC tumors. This opens a new field to cancer prevention.
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PMID:Prognostic significance of molecular biological and immunohistological parameters in gastrointestinal carcinomas. 889 36

There is an increased prevalence of p53 mutations in hepatocellular carcinomas (HCCs). A total of 62 HCC samples with adjacent liver tissue were analyzed immunohistochemically for the presence of p53 by two different commercial sources of Pab 1801. Polyclonal antibodies anti-HbsAg and anti-HbcAg were employed for the detection of HBV in the adjacent tissue and PC-10 for the detection of proliferating cell nuclear antigen (PCNA). Positive staining for p53 was identified in 42% and 55% of the HCC cases using each monoclonal antibody. p53 was found in 42% of the low grade and 43% of the high grade HCC. In 32% of the HCC cases, p53 was found in the adjacent liver tissue. In 52.6% of the cases with evidence of HBV infection, p53 positive expression was observed. PCNA was detected in 56% of the HCC cases (69% low grade, 57% high grade HCC). Eighty-one percent of the p53 positive tumours expressed PCNA, mostly with a high index. p53 and PCNA were not related to histologic grade. A trend for positive correlation was observed between p53 expression and HBV infection. The detection of p53 in non neoplastic tissue and the absence of a significant correlation between p53 expression and degree of differentiation support the hypothesis that the p53 gene mutation is involved in early stages of hepatocellular carcinogenesis.
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PMID:Immunohistochemical expression of p53 protein and proliferating cell nuclear antigen in hepatocellular carcinoma. 892 68

Mice bearing the autosomal recessive mutation 'wasted' (wst/wst) express a disease syndrome characterized by neurologic dysfunction, immunodeficiency, and increased sensitivity to the killing effects of ionizing radiation relative to normal littermates (wst/-) and to parental control mice (BCF1, BALB/c, and C57BL/6). Many of these abnormalities, evident as early as 21 days of age, have been localized to thymic tissues and T-lymphocyte populations. Comparison of two-dimensional gel electrophoresis patterns of proteins from wst/wst and control mouse thymus revealed that an acidic protein with a molecular mass of approximately 30 kDa was consistently expressed at lower levels in wasted mice than in controls. Microsequencing of this protein revealed a sequence of 19 N-terminal amino acids identical to the sequence of murine proliferating cell nuclear antigen (PCNA). Northern blot analyses of PCNA expression in thymus and spleen demonstrated lower accumulation of PCNA-specific transcripts in wasted mice compared with that in controls. Because PCNA expression is associated with cell cycle progression, the percentages of thymic and splenic cells in each stage of the cell cycle were examined; there were no differences in the cell stage distribution of lymphocytes freshly isolated from wasted mice compared with littermate or parental controls. After activation with concanavalin A, however, splenocytes from wst/wst mice showed a lower percentage of cells in S phase compared with that in controls. Southern blots with PCNA probes showed that the PCNA loci from the wasted mice and their normal littermates have the same restriction maps. While differences in polymerase chain reaction (PCR) priming were obtained, these could be attributed to strain-specific differences in mouse PCNA pseudogenes. These results suggest the presence of an alteration in the pathway leading to PCNA expression in radiation-sensitive tissues of wasted mice.
Carcinogenesis 1996 Nov
PMID:Regulation of thymus PCNA expression is altered in radiation-sensitive wasted mice. 896 49


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