Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04626 (erbB-2)
 5,251 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

K1 is a murine monoclonal antibody (MAb) derived from a hybridoma generated by the fusion of splenocytes of BALB/c mice immunized with a human ovarian tumor cell line, OVCAR-3. This antibody reacts strongly with epithelial ovarian tumors and mesotheliomas. The antigen recognized by MAb K1, designated CAK1, has recently been characterized as a 40-kDa protein probably anchored to the cell surface by glycosyl-phosphatidylinositol. Using immunoperoxidase histochemical methods, we examined 37 squamous-cell carcinoma (SqCC) samples from cervix, lung, esophagus and other origins, and 12 normal squamous epithelia of the cervix and esophagus for their reactivity with MAb K1. Of the SqCC specimens, 81% showed K1 reactivity with variable intensity, but none of 12 normal tissue samples of squamous epithelia did so. Two patterns of CAK1 expression in tumor samples were found, i.e., a heterogeneous pattern with strong intensity, and a homogeneous pattern with weak intensity. Three carcinomas in situ of the larynx, vulva and esophagus were moderately positive with K1, suggesting that CAK1 antigen may occur in the early stage of carcinogenesis of SqCC. The expression of CAK1 was also compared with expression of CA125, HER-2/neu, p53 and P-glycoprotein, and MAb K1 was found to react most consistently with SqCC. Since K1 reacts with a majority of cervical and esophageal carcinomas but has no detectable reactivity in normal epithelia of the cervix uteri and esophagus, MAb K1 could be of value as a reagent to help distinguish between normal and neoplastic cells on sections as well as in cytological samples.
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PMID:Frequent expression of the tumor antigen CAK1 in squamous-cell carcinomas. 135 Oct 45

The effects of treatment in a hydrated autoclave (121 degrees C, 2 atm for 20 min), microwave oven (in water), and simple heating (60 degrees C overnight in distilled water or 90 degrees C for 10 min in ZnSO4) on the stainability of 56 antigens by commercially available antibodies in formalin-fixed paraffin-embedded tissue sections were evaluated. The detectability of nuclear antigens, glycoprotein, lymphocytic surface markers, and chromogranin A was significantly and reproducibly improved by these treatments, whereas the detectability of viral antigens and peptide hormones was attenuated or unchanged. This enhancement includes not only the distinctiveness of the positive staining, but also the number of positive cells, as revealed by comparing serial sections. Among these four heating procedures, microwave heating and autoclaving were more effective than the others on p53, c-erbB-2, and CA125, whereas simple heating was best for smooth-muscle actin (HHF35 and CGA7). Generally the effects of the heating procedures for these antigens were consistent among the cases, but the effects on GFAP varied with the case. The alterations we observed could significantly influence the interpretation of immunohistochemical staining of currently popular tumor markers such as p53 in terms of their prevalence (28% vs 64% in gastric cancer; 36% vs 82% in metastatic liver cancer) and other diagnostically important markers.
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PMID:Alteration of immunoreactivity by hydrated autoclaving, microwave treatment, and simple heating of paraffin-embedded tissue sections. 751 73

An epithelial ovarian cancer cell line is established from a patient with recurrent familial ovarian cancer. Two of the patient's sisters and her mother have also had ovarian cancer. The histological resemblance of the cell line to the patient's Stage IV, Grade 3 papillary serous ovarian primary cancer is striking. The cell line does not secrete CA125 and is estrogen and progesterone receptor negative. Overexpression of the p53 tumor suppressor gene but not the HER-2/neu oncogene was detected by immunohistochemical analysis. An unusual chemosensitivity to cisplatin, doxorubicin, etoposide, and taxol is demonstrated, suggesting that a chemosensitivity mechanism might explain prolonged survival of some patients with familial ovarian cancers. This truly unique cell line should prove invaluable in the further evaluation of molecular genetic changes associated with familial ovarian cancers.
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PMID:Isolation and preliminary characterization of an ovarian carcinoma cell line from a patient with familial ovarian cancer. 782 46

A cell line derived from human endometrial clear cell adenocarcinoma was newly established and named TEN. The tumor cells were obtained from uterine body of a 74-year-old who had been undergone an abdominal simple hysterectomy. The histologic features of the tumor cells showed abundant clear cytoplasm with diastase digested glycogen granule growing in solid nest and tubular pattern. The TEN cells were continuously propagated in vitro during the past 45 months and they were at 75th passage. They grew in a monolayered sheet with a doubling time of about 53 hours. The TEN cells resembled the structure of the original tumor and had abundant glycogen granules, lipid droplets in the cytoplasm. The histopathology of the transplanted tumor in SCID mice resembled that of the original tumors. The TEN cells secreted a high content of CA125. Immunohistochemically, the TEN cells had c-erbB-2 and Cathepsin D immunoreactivity in some parts of the cell population. But they did not have estrogen, progesterone and EGF receptor. Sensitivities of the TEN cells to a variety of anti-cancer drugs were examined. In in-vitro tests, MTT assays employed. The results suggested that the TEN cells were not sensitive to any of 13 agents. On the other hand, in-vivo sensitivity test of transplanted tumor in SCID mice, the tumors were sensitive to CPT-11 and paclitaxel. We conclude that the TEN cell line will be effective material for chemosensitivities against the endometrial clear cell adenocarcinoma.
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PMID:Characterization of a newly established human tumor cell line (TEN) from a patient with clear cell carcinoma of the uterine body and its sensitivity to anti-cancer agents. 943 40

We examined gene amplifications of the c-erbB-2 and FGF-3 gene in 48 epithelial ovarian cancers by differential PCR and addressed their association with clinico-pathological features including clinical outcome. Overall, 25.0 and 20.8% of ovarian cancers displayed amplified c-erbB-2 or FGF-3 gene, respectively. Amplification of the c-erbB-2 gene was significantly associated with particular histological cell types, higher histological grade, and low levels of serous CA125. However, there was no correlation between c-erbB-2 gene amplification and patient outcome. No correlation was observed between FGF-3 gene amplification and any clinico-pathological features including overall survival. These findings suggested that c-erbB-2 or FGF-3 gene amplification might be one of the oncogenic events implicated in the development of ovarian cancers, yet is not a useful prognostic marker.
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PMID:Detection of c-erbB-2 and FGF-3 (INT-2) gene amplification in epithelial ovarian cancer. 1085 25

The purpose of this Phase I study was to determine the feasibility of using an anti-erbB-2-encoding adenovirus (Ad21) to treat erbB-2-overexpressing ovarian cancer. Recurrent ovarian cancer patients were treated i.p. with Ad21 in dosages ranging from 1 x 10(9) to 1 x 10(11) pfu. Patients were monitored after treatment for evidence of clinical toxicity and efficacy. Peritoneal aspirates and serum samples were obtained to assess for evidence of gene transfer/expression, for generation of wild-type vector, and antiadenoviral humoral response. Fifteen patients were treated per study specifications. Treatment-specific grade 1/2 fever was experienced by 9 of 15 (60%) patients. Other transient grade 1/2 constitutional, pain, and gastrointestinal symptoms were also experienced. No dose-limiting vector-related toxicity was experienced. Of 13 patients evaluable for response, 5 (38%) had stable disease and 8 (61%) had evidence of progressive disease. One patient with nonmeasurable disease normalized her CA125 at the 8-week evaluation, and one patient with nonmeasurable disease remained without clinical evidence of disease for 6 months after treatment. PCR analysis of peritoneal aspirates demonstrated the presence of Ad21 in 84.6%, 84.6%, and 61.6% of evaluable specimens at days 2, 14, and 56 after treatment, respectively. No wild-type virus was detected. Reverse transcription-PCR analysis demonstrated expression of the anti-erbB-2 sFv-encoding gene in 10 of 14 evaluable patients at day 2. Five of six evaluable patients had an increase in antiadenovirus antibody titer. This study suggests that adenoviral-mediated gene therapy using an anti-erbB-2-directed intrabody is feasible in the context of human ovarian cancer.
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PMID:A cancer gene therapy approach utilizing an anti-erbB-2 single-chain antibody-encoding adenovirus (AD21): a phase I trial. 1095 87

Ovarian cancer screening protocols generally have been limited by inadequate recognition of the normal behavior of tumor markers in women at risk of ovarian cancer. We have characterized the behavior of five serum tumor markers in a large cohort of healthy women and examined the implications for screening. Serial measurements of CA125, HER-2/neu, urinary gonadotropin peptide, lipid-associated sialic acid, and Dianon marker 70/K were obtained during 6 years of follow-up of 1257 healthy women at high risk of ovarian cancer. We analyzed individual-specific tumor marker behavior and explored methods that can exploit this information to develop individual-specific screening rules. These five tumor markers behaved approximately independently. Substantial heterogeneity was observed among women in the behavior of each tumor marker, particularly CA125. Intraclass correlation (ICC), or the proportion of total variability that occurs between individuals, was approximately 0.6 for log-transformed CA125 and urinary gonadotropin peptide, and less than 0.4 for the other markers. This degree of tumor marker heterogeneity among healthy women, and the relative independence of these markers, has important implications for screening and diagnostic tests. Independence of markers results in the clinically useful fact that the combined false positive rate from screening with multiple markers may be estimated by the sum of individual false positive rates. Heterogeneity of tumor marker patterns in healthy women implies that a fixed screening cutoff level is suboptimal to a degree that depends strongly on ICC. Using information on longitudinal measurements and ICC, individual-specific screening rules may be developed with the potential to improve early detection of ovarian cancer.
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PMID:Ovarian cancer tumor marker behavior in asymptomatic healthy women: implications for screening. 1104 95

The role of urokinase plasminogen activator receptor (uPAR) and c-erbB-2 in breast and ovarian cancer was investigated. Eighty patients of breast and ovarian cancer and benign lesions, as well as twenty normal controls were evaluated for the expression of c-erbB-2 by Western blotting and uPAR levels by ELISA. The c-erbB-2 and uPAR showed a significant increase in both types of cancer investigated compared to normal control and benign lesions. The frequency of c-erbB-2 was significantly higher in breast cancer lesions (p < 0.01). Levels of CA15.3 in breast cancer and CA125 in ovarian cancer were significantly higher in cases expressing c-erbB-2 (p < 0.01) than in negative c-erbB-2 cases. The uPAR showed a significant positive correlation with advanced stages of breast cancer (r = 0.7971) and ovarian cancer (r = 0.83662), while significant correlations were found for CA15.3 in breast cancer (r = 0.64967) and CA125 in ovarian cancer (r = 0.83996). Taken together, our data suggest that the c-erbB-2 and uPAR in the sera of ovarian and breast cancer act as valuable markers for the evaluation of the patients preoperatively.
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PMID:Detection of urokinase plasminogen activator receptor and c-erbB-2 in sera of patients with breast and ovarian carcinoma. 1456 47

The prognostic value of p53 and c-erbB-2 immunostaining and preoperative serum levels of CEA and CA125 was investigated in a prospective multicentric study including 465 consecutive non-small cell lung cancer (NSCLC) patients with resectable tumors. Four end-points were used: lung cancer death, first relapse (either locoregional or metastasis), loco-regional recurrence and metastasis development. Standard statistical survival methods (Kaplan-Meier and Cox regression) were used. The specificity of the prognostic effect across different types of tumors was also explored, as had been planned in advance. Our results showed, once again, that pathological T and N classifications continue to be the strongest predictors regarding either relapse or mortality. Three of the studied markers seemed to add further useful information, however, but in a more specific context. For example, increased CEA concentration defined a higher risk population among adenocarcinomas but not among people with squamous tumors; and p53 overexpression implied a worse prognosis mainly in patients with well differentiated tumors. The analysis of type of relapse proved to be very informative. Thus, CA125 level was associated with a worse prognosis mainly related with metastasis development. Another interesting result was the influence of smoking, which showed a clear dose-response relationship with the probability of metastasis. For future studies, we recommend the inclusion of different endpoints, namely considering the relationship of markers with the type of relapse involved in lung-cancer recurrence. They can add useful information regarding the complex nature of prognosis.
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PMID:Clinical value of p53, c-erbB-2, CEA and CA125 regarding relapse, metastasis and death in resectable non-small cell lung cancer. 1456 28