Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0596263 (carcinogenesis)
 64,820 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumor registry data indicate a two- to fourfold increased incidence of breast cancer following mantle irradiation, but cumulative risk is unknown. Radiation exposure to the breasts underlying the mantle block ranges from 4 to 40 Gy and is dependent on relative positions of the breasts and mantle block. Unshielded outer breast quadrants near axillary nodal regions receive 36 to 40 Gy, while central breast quadrants under the lung blocks receive approximately 4 Gy as determined by dose volume histogram analysis. Relative dose risk analysis for breast cancer following mantle irradiation was performed and indicated an overall excess risk of 1.5 for the upper outer quadrant (total dose 40 Gy), 1.3 for the upper and lower inner, and central quadrants (total dose 15 to 20 Gy), and 1.2 for the lower outer quadrant (total dose 4 Gy). Linear and cell-kill carcinogenesis models demonstrated similar relative risk assessments in the low-dose regions, defined as < 15 Gy. Predicted risk for breast cancer in the high-dose regions (> or = 15 Gy) varied considerably according to the model evaluated. The linear model predicted a three to ten times greater risk above baseline breast cancer incidence for the high-dose regions. In contrast, the cell-kill model predicted no excess cases of breast cancer, assuming cell death at these higher dose levels. The greatest relative predicted risk is observed in women < 20 years of age at the time of irradiation; however, women older than 20 years continue to have a 50% higher than baseline risk for subsequent breast cancer development. All women treated for Hodgkin's lymphoma should undergo dose volume histogram evaluation. Prospective clinical and mammographic evaluations should be performed in all female patients following mantle irradiation to better define the risk for secondary breast carcinogenesis.
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PMID:Calculated risk of breast cancer following mantle irradiation determined by measured dose. 147 17

Curative treatment for Hodgkin's disease for patients who are pathology-staged IIIA, spleen-positive, consisted of total nodal irradiation (TNI) alone at the University of Minnesota Hospitals prior to 1975. This approach has been modified since 1975 to give low-dose irradiation to the liver in addition to TNI because of the high recurrence rate with TNI alone. Recurrence-free survival improved significantly when the liver was irradiated as compared to results with TNI alone (78% vs. 41% at 5 years, p = 0.004). The 5-year, overall survival was not significantly different in the two groups (90% vs. 80% at 5 years, p = 0.373). Various prognostic factors were examined. Patients who received liver treatment had statistically significant improvement in recurrence-free survival as compared to patients who did not receive liver treatment in the following categories: anatomic substage IIIA1, histologic classification of nodular sclerosis, male gender, age less than 40, number of primary sites, and extent of splenic disease. However, these factors failed to show clinical significance as prognostic factors. We conclude that TNI with low-dose liver irradiation should be used as the primary modality of treatment of Hodgkin's disease, pathology-staged IIIA patients. We conclude that chemotherapy should be reserved for recurrences in view of the excellent current results and the lesser risk from treatment, especially the risk of carcinogenesis.
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PMID:Liver irradiation in stage IIIA Hodgkin's disease patients with splenic involvement. 670 19

Instability of dinucleotide tandem repeat sequences has been reported to play a major role in the carcinogenic pathway of familial colon cancer, as well as a potential role in the carcinogenesis of other sporadic neoplasms. To determine the frequency of short tandem repeat instability in adenocarcinoma of the prostate, we studied 40 tumors that were stratified according to tumor grade. The tissue samples were screened with di-, tri- and tetranucleotide markers spanning a wide range of chromosomal loci, including an androgen receptor gene trinucleotide repeat. Microsatellite instability was observed overall in only one of the 40 (2.5%) prostate adenocarcinomas studied. This replication error-positive tumor demonstrated repeat length alterations at two loci. Five other tumors showed an alteration in microsatellite size at a single locus. These tumors were not considered to have the microsatellite instability phenotype. All changes were identified either within tetranucleotide sequences or within the androgen receptor gene repeat (4 or 20 total markers analyzed). Both repeat length expansions and contractions were identified. The replication error-positive case also included separate metastatic nodal tissue. Additional microsatellite analysis of the metastatic tumor tissue revealed allelic patterns identical with the normal tissue control. Our data indicate that microsatellite instability is rare in prostate adenocarcinoma. Therefore, observation of this low replication error frequency suggests that most prostate carcinomas develop in the absence of widespread accumulation of somatic mutations in short tandem repeat sequences. Additionally, these genetic alterations appear to occur more often in tetranucleotide repeat sequences as well as in an androgen receptor gene trinucleotide repeat.
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PMID:Microsatellite instability in adenocarcinoma of the prostate. 767 91

The bcl-2 gene provides a window on the basic cellular machinery of apoptosis or programmed cell death, a process involved in virtually all biologic events in multicellular organisms, but particularly relevant to neoplasia and development. bcl-2 gene function supports cell survival and appears to lie at a nodal point in pathways leading to activation or execution of apoptosis. Carcinogenesis may involve several steps at which cell death programs are normally activated and are bypassed in cancer cells, including apoptotic pathways activated by several oncogenes. Functional redundancy and the complexity of the regulation of cell survival are demonstrated by the less than expected phenotype of bcl-2 knockout mice and the cloning of several bcl-2 related genes, some of which promote cell death. The molecular function for bcl-2 is unknown, but several lines of evidence support a role in protection from oxidative stress. These studies suggest that many environmental perturbations and genetic pathways converge to disrupt a metabolic balance between oxidant generation and anti-oxidant defenses.
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PMID:bcl-2 in cancer, development and apoptosis. 788 92

To verity the role of metastasis-related nm23 genes in carcinogenesis and progression of ovarian carcinoma, we analyzed the mRNA levels of the nm23 genes of both isoforms, -H1 and -H2, together with those of the epidermal growth factor receptor, the c-erbB-2, and the c-erbB-3 genes in 45 ovarian carcinomas and 5 benign cystadenomas. Expressions of nm23 gene products/nucleoside diphosphate kinases, epidermal growth factor receptor, erbB-2 protein, and sex steroid receptor status in ovarian carcinomas were also examined by immunohistochemistry. The mRNA levels of nm23-H1 and nm23-H2 were higher in carcinoma tissues compared with benign tumors (H1, P < 0.01). The mRNA levels of c-erbB-2 and c-erbB-3 were also elevated in carcinoma tissues, and there was a positive correlation between mRNA levels of the nm23-H1 and the c-erbB-2 genes (r = 0.58; P < 0.05). Correlation of immunohistochemical staining between nucleoside diphosphate kinases and erbB-2 protein was also observed in ovarian carcinoma tissues. Sex steroid receptor positivity was related to a higher expression of nucleoside diphosphate kinases. Expression levels of the nm23 genes in ovarian carcinomas were not related to either histological subtype or local extension and peritoneal dissemination. Among stage III ovarian carcinomas, however, tumors possessing lymph node metastasis showed significantly lower nm23-H1 mRNA levels than those without nodal involvement (P < 0.05). Stage IV carcinomas also exhibited lower nm23-H1 and nm23-H2 expression levels compared with other stages (P < 0.05). These results suggest that expression of the nm23 genes, especially nm23-H1, is activated, accompanied by c-erbB-2 and c-erbB-3 overexpressions, in early stages of the carcinogenic process of ovarian carcinoma and reduction of nm23-H1 expression occurs in association with lymph nodal and/or distant metastasis.
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PMID:Expression of metastasis-related nm23-H1 and nm23-H2 genes in ovarian carcinomas: correlation with clinicopathology, EGFR, c-erbB-2, and c-erbB-3 genes, and sex steroid receptor expression. 790 45

Basic fibroblast growth factor (bFGF), a potent angiogenic peptide, is thought to provide a growth advantage to a number of tumors including squamous cancer of the head and neck. The purpose of this study was to demonstrate the in situ expression of bFGF in lesions of the upper aerodigestive tract (UADT) and to correlate that with clinical parameters and known risk factors for carcinoma. On surgical specimens from 52 patients, we used a colorimetric in situ hybridization assay to determine the expression of bFGF mRNA in normal and pathologic conditions commonly seen in squamous mucosa. The extent of reactivity for the bFGF transcript was recorded on a subjective scale from 1+ to 3+, based on the visual intensity of labeling. These findings were subsequently correlated with clinical data. Basic fibroblast growth factor mRNA was detected at low to moderate levels in all sections of normal mucosa, with no distinction between patients with or without squamous cancer. Inflamed mucosa had comparatively strong expression of bFGF mRNA. Among lesions implicated in the stepwise nature of squamous carcinogenesis, we found increases in bFGF expression that were most significant at the level of carcinoma in situ, persisting through the invasive and nodal metastatic stages of the disease (P < 0.005). Interestingly, those increases were significantly less frequent among former smokers (P = 0.02). We have established the expression of bFGF mRNA in normal, inflammatory, and neoplastic tissue within the UADT. Furthermore, we note for the first time that increased expression is associated with the acquisition of more aggressive biologic behavior in squamous carcinogenesis.
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PMID:Increased expression of basic fibroblast growth factor in squamous carcinogenesis of the head and neck is less prevalent following smoking cessation. 797 55

It is known that E2 protein of oncogenic human papillomavirus (HPV) inhibits the expression of E6 and E7 genes from their major promoters in vitro and suppresses the proliferation of cervical cancer cells. This suggests that the loss of functional E2 gene may provide selective advantages in the development of cervical cancer. Investigation of the relationship between the disruption of HPV-16/18 E2 genes by DNA integration and clinical outcome of cervical cancer may not only help to understand the mechanism of HPV-related cervical carcinogenesis, but may also provide novel management of cervical cancer. It was noted that integrated HPV-16/18 DNA was predominant in most patients with cervical cancers, marking 51 of a total of 68 cases (75%); episomal HPV DNAs were found in 5 cases (7.4%), and finally mixed forms of HPV DNAs with episome and integration were found in 12 cases (17.6%). Whole portions of E2 DNA of HPV-16 could be amplified by PCR in 19 (36.5%) of 52 cases of cervical intraepithelial neoplasia. It was shown that there was not statistically significant association with the different stages, but integrated HPV DNAs were detectable only in the patients with far-advanced stage of cervical cancers, which also means no episomal forms were detected. Episomal forms of HPV DNA were detectable in 14 (25.9%) of 54 squamous cell carcinomas (4 pure episomal forms and 10 mixed forms), whereas only 1 (8.3%) of 12 adenocarcinomas and adenosquamous cell carcinomas contained episomal viral DNA. When HPV DNA forms were compared with initial tumor size, lymphovascular space involvement, and frequency of nodal metastasis, statistically significant relationships were not found. The association of DNA integration with invasive cervical cancers was seen regardless of HPV type; however, there were differences between the integration profiles of HPV-16 and HPV-18 DNA. Of the 51 HPV-16-containing cancers, 36 (70.6%) revealed purely integrated HPV DNA, and another 10 cases (19.6%) displayed both integrated and episomal HPV DNAs. However, 5 (9.8%) cases showed only episomal copies of the HPV-16 genome. In contrast, all 17 HPV-18-containing cancers (5 cases positive for HPV-18 and 12 cases positive for both HPV-16 and -18) revealed only the integrated form of HPV-18 DNA. The expression of E6 and E7 transcripts of HPV-16/18 is uniformly correlated with the physical status of HPV DNAs. HPV E2 mRNAs were constantly expressed in the presence of the intact virus in cases with episome and mixed forms of HPV DNA. In general, amplified signals from HPV E2 RT-PCR are more intensive than those from DNA-PCR in the same patients. It is suggested that RT-PCR is a valuable method to evaluate dynamic expression of the specific gene and seems to be more sensitive than the DNA-PCR method in detecting intact E2 gene because of the gene copy numbers.
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PMID:Physical status and expression of HPV genes in cervical cancers. 910 1

In order to clarify critical events during bronchial carcinogenesis, and to evaluate a possible prognostic role for p21 immunohistochemical detection, we assessed the immunohistochemical expression of p21 protein in 60 surgically resected non-small-cell lung cancers (NSCLCs) that had been investigated previously for their p53 protein status. We found that p21 protein was expressed in both normal and neoplastic tissue. In normal tissue, p21 immunoreactivity was detectable in a low percentage of well-differentiated cells. We found immunostaining for p21 in 80% of the investigated neoplasms. In 73.3% of the neoplasms, p21 was considered to be overexpressed. No relationship was found between p21 overexpression and tumor stage or tumor-nodal-metastatic (TNM) status. The histologic grading was slightly correlated with the p21 status (P = -0.51), with no significant differences noted between squamous carcinomas and adenocarcinomas. Survival percentage curves for our lung-cancer patients, based on a comparison of different p21 expression levels and constructed through a Kaplan-Meier analysis, showed significant differences in mean (P < 0.001) and overall (P < 0.001) survival time between patients of different p21 status, suggesting a favorable prognostic value of p21 immunostaining for NSCLC patients.
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PMID:p21waf1/cip1mda-6 expression in non-small-cell lung cancer: relationship to survival. 947 8

This study used lectins as histologic probes to determine the cell surface oligosaccharide expression in different grades and types of vulvar intraepithelial neoplasia (VIN). Lectin binding patterns in metastasizing and non-metastasizing squamous cell carcinomas (SCCs) of the vulva were also compared to correlate lectin binding patterns with metastatic potential and other clinical/tumor characteristics. Twenty cases each of VIN epithelium, metastasizing SCC, and non-metastasizing vulvar carcinoma were randomly chosen from the pathology archives. Sixteen lectins were used to probe individual terminal oligosaccharide residues in formalin-fixed, paraffin-embedded tissue specimens from these cases through an indirect immunohistochemical technique. There were no differences in lectin binding patterns between the different histologic subtypes of VIN. In addition, there were no consistent differences between metastasizing and non-metastasizing primary tumors and no major differences in staining patterns between nodal metastases and the corresponding primary tumors. Furthermore, there was no identifiable correlation between lectin binding patterns and subsequent survival or local or regional recurrence; however, lectin staining of invasive tumor cells did appear to be related to local invasiveness. In addition, positive PNA binding was found to be a constant finding in each of the VIN and invasive SCC cases, confirming that the T-antigen becomes unmasked during the process of vulvar carcinogenesis. However, poorly-differentiated areas consistently showed absent lectin binding, suggesting loss of specific glycosyl transferase activities. In addition, the blood group "A" antigen appears to be lost during the process of tumorgenesis, although the blood group "O" antigen appears to be preserved.
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PMID:Lectins in the vulva. II. Vulvar intraepithelial neoplasia and squamous cell carcinoma. 955 14

We report herein the unusual case of a 59-year-old woman with Plummer-Vinson syndrome who developed gastric cancer. The patient had a longstanding history of dysphagia and iron deficiency anemia, for which she had sporadically taken iron supplements that improved the dysphagia to some extent, but not completely. Owing to her tolerance of the dysphagia, she had not been taking iron supplements for the past 17 years. On admission, she was in fair nutritional condition and not anemic. Blood chemistry results were all normal, including the serum iron level. Gastrointestinal radiographic series demonstrated cervical esophageal webs and advanced gastric cancer. Her dysphagia was successfully treated by endoscopic bougienage through the webs, and a distal partial gastrectomy with nodal dissection was performed. Histology of the resected stomach revealed atrophic mucosal change and, by chance, an adenomatous lesion in addition to adenocarcinoma. Her postoperative course was uneventful and she is now well, without any signs of recurrence. Although Plummer-Vinson syndrome is known to be associated with upper alimentary tract cancers, gastric cancer is extremely rare. A discussion on the etiology of Plummer-Vinson syndrome and its link with potential carcinogenesis follows this case report.
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PMID:Gastric cancer occurring in a patient with Plummer-Vinson syndrome: report of a case. 978 78


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