Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tumoral biological markers of breast cancer expand the predictive value of conventional prognostic factors, such as tumor size, axillary lymph node status, and histoprognostic grade. They include tumor estrogen and progesterone receptor levels, flow cytometric DNA analysis, to convey a prognostic value. Expression of the product of the gene pS2, which reflects the functional integrity of the estradiol receptor, indicates a good prognosis. In contrast, presence of growth factor receptors, such as the EGF receptor, or amplification of the HER2/neu or INT2 oncogene indicate a poor prognosis. Study of protein gp 170 and GST-pi predicts the response of tumors to chemotherapy, while the study of the potential doubling time (Tpot) provides an indication of the renewal capacity of the tumor. Markers of tumor invasiveness and metastatic potential include proteases (activators and inhibitors) produced either by tumor cells or by the cells of the stroma, gene nm 23, and membrane fatty acids. The place of the last markers in patients' treatment is not known yet. The knowledge of the tumor biological parameters along with clinical features should provide an accurate prediction of the aggressiveness of the tumor, allowing the best adjustment of treatment with the expected behavior of the disease.
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PMID:[Intratumoral biological markers in breast cancers]. 148 91

We report a linkage between cell aggressiveness, protein kinase C (PKC) activity, tyrosine kinase (PTK) activity and serum requirement. We used 2 leukemic cell lines induced by Moloney murine leukemia virus (MLV). One line was highly aggressive (BS-24-1) and required low serum concentrations (3%) for optimal growth in comparison to the less aggressive line (RO2T) that needed 10% serum for optimal growth. The more malignant cells exhibited higher PKC and PTK activity. This activity was independent of serum concentration between 0.01-10%. In contrast, the weakly malignant cells need a high serum concentration (10%) for optimal PKC or PTK activity. Immunoblot analysis revealed a higher level of PKC protein in the BS-24-1 cells than in the RO2T cells. Serum induction of PKC activity did not change the amount of PKC protein in the cytosol or the membrane fractions, indicating post-translational mechanism regulation of PKC. We suggest that the aggressiveness of BS-24-1 resulted from its ability to become independent of growth regulation by serum factors, via autocrine stimulation of PKC and PTK.
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PMID:Elevated activities of protein kinase C and tyrosine kinase correlate to leukemic cell aggressiveness. 172 4

The retinoid N-(hydroxyphenyl) retinamide (4-HPR) appears to be a promising tool for chemoprevention of breast carcinoma, and clinical trials to evaluate its effect are in progress. However, its action on tumor cells has remained largely undefined. We report here that 4-HPR induced apoptosis and/or differentiation in breast cancer cell lines, independent of hormone receptor status and retinoic acid receptor expression, although it was slightly more efficient in inhibiting proliferation of estrogen receptor-positive cells. 4-HPR up-modulated expression of several differentiation markers (class 1 HLA, laminin, and beta 1 integrin chain) and down-regulated expression of molecules associated with tumor progression, including the p185/HER2 oncoprotein, the epidermal growth factor receptor, and the M(r) 67,000 laminin receptor. These data suggest that 4-HPR could exert a beneficial effect by inhibiting cell proliferation and modulating breast tumor aggressiveness.
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PMID:Modulation of markers associated with tumor aggressiveness in human breast cancer cell lines by N-(4-hydroxyphenyl) retinamide. 754 8

The expression of Cath-D c-erbB-2 and EGFR in breast cancer and its correlation of lymphatic metastases were studied in 277 cases by immunohistochemical technique. Positive staining of Cath-D was detected in 107 cases (38.62%), of which, 89 cases (83.17%) had documented metastasis in the lymph nodes. One hundred and seventy cases (61.38%) stained negative for Cath-D, of which 64 cases (37.64%) had detectable lymphatic metastases. There was a significant difference in the rate of the lymphatic metastases between the Cath-D positive and Cath-D negative groups (P < 0.0001). Fifty-six out of 107 Cath-D positive cases (52.34%) were c-erbB-2 positive as well. However, only 27 out of 170 Cath-D negative cases (15.88%) were c-erbB-2 positive. The positive rate of c-erbB-2 in Cath-D positive group was significantly different from that of Cath-D negative group (P < 0.0001). Among those 107 Cath-D positive cases, 49 cases (45.79%) were EGFR positive. Only 24 cases (14.12%) were EGFR positive among the 170 Cath-D negative cases. The positive rate of EGFR between these two groups was also significantly different (P < 0.0001). The results suggest that Cath-D status can be used as an indicator of the aggressiveness of the breast cancer. Breast cancer cases with a positive Cath-D staining are more likely to have lymphatic metastases and a poor prognosis. Therefore, alternative therapeutic strategies and close follow-ups are needed for these patients.
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PMID:[The expression of Cath-D, c-erbB-2 and EGFR in breast cancer and its correlation to lymphatic metastasis]. 765 92

The AKT2 gene is one of the human homologues of v-akt, the transduced oncogene of the AKT8 virus, which induces lymphomas in mice. In previous studies, AKT2, which codes for a serine-threonine protein kinase, was shown to be amplified and overexpressed in some human ovarian carcinoma cell lines and amplified in primary tumors of the ovary. To confirm and extend these findings, we conducted a large-scale, multicenter study of AKT2 alterations in ovarian and breast cancer. Southern-blot analysis demonstrated AKT2 amplification in 16 of 132 (12.1%) ovarian carcinomas and in 3 of 106 (2.8%) breast carcinomas. No AKT2 alteration was detected in 24 benign or borderline tumors. Northern-blot analysis revealed overexpression of AKT2 in 3 of 25 fresh ovarian carcinomas which were negative for AKT2 amplification. The difference in the incidence of AKT2 alterations in ovarian and breast cancer suggests a specific role for this gene in ovarian oncogenesis. No significant association was found between AKT2 amplification and amplification of the proto-oncogenes MYC and ERBB2, suggesting that amplification of AKT2 defines an independent subset of breast and ovarian cancers. Ovarian cancer patients with AKT2 alterations appear to have a poor prognosis. Amplification of AKT2 was especially frequent in undifferentiated tumors (4 of 8, p = 0.019), suggesting that AKT2 alterations may be associated with tumor aggressiveness.
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PMID:Molecular alterations of the AKT2 oncogene in ovarian and breast carcinomas. 765 93

In order to examine whether the expression of the oncoproteins might be important for the malignancy of tumors, the relationship between the take rate of 88 human squamous cell lung carcinomas in nude mice and the expression of protooncogene products was analyzed. The expression of c-fos, c-jun, c-ras, c-erbB1, c-neu and c-myc at the protein level was investigated by immunohistochemistry. Tumor take was assumed if within three months growing nodules were detected and confirmed histologically. The take rate of squamous cell lung carcinomas in nude mice was 49%. Sixty-eight percent of the tumors were positive for Fos, 40% for Jun, 67% for Ras, 77% for ErbB1, 35% for Neu and 39% for Myc. Tumors with an (over)expression of the proteins encoded by the oncogenes c-fos, c-jun, c-erbB1 and c-ras had a significantly higher take rate in nude mice than tumors without an (over)expression of the oncogene products. In contrast, the expression of the c-neu and the c-myc genes at the protein level had no influence on the take rate of the tumors in nude mice. Interestingly, only patients with tumors with an (over)expression of the proteins encoded by the oncogenes c-fos, c-jun, c-erbB1 and c-ras had significantly shorter survival times than patients whose tumors did not show an (over) expression of the oncogene products. These results demonstrate that the aggressiveness of the tumors visible in the higher take rate of the tumors in nude mice and in the shorter survival times of patients can be detected by measurement of the expression of c-fos, c-jun, c-erbB1 and c-ras at the protein level.
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PMID:Correlation between successful heterotransplantation of lung tumors in nude mice, poor prognosis of patients and expression of Fos, Jun, ErbB1, and Ras. 829 9

Platelet monoamine oxidase (MAO) activities were determined in 58 non-psychotic males at forensic psychiatric examinations. The aim of the study was to investigate the role of platelet MAO activity as a biological marker in forensic psychiatry, a clinical field with growing need of safe predictors for both treatment outcome and behavior. The study population was heterogeneous with respect to clinical and personality disorders and personality traits. The results confirmed the role of platelet MAO activity as a biological marker for stable personality traits such as impulsiveness, monotony avoidance and aggressiveness. Disorders with high frequencies of these personality traits such as borderline personality disorder and type II alcoholism could secondarily be associated with low levels of platelet MAO activity, whereas no such associations could be found regarding other clinical or personality disorders. Neither psychopathy as assessed by the means of PCL-R nor behavior such as abuse or criminality could be associated with platelet MAO activity. The conclusion is that, due to its close relationship with stable personality traits, platelet MAO activity serves a marker for vulnerability also in forensic psychiatric populations. On the other hand it is not a marker for clinical or personality disorders, or behavior per se.
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PMID:Platelet monoamine oxidase activity as a biological marker in a Swedish forensic psychiatric population. 910 75

Malignant tumors of the thyroid gland vary considerably in aggressiveness, ranging from a well-differentiated, clinically indolent, to an undifferentiated, often lethal phenotype. Undifferentiated (anaplastic) thyroid tumors are supposed to be derived, through a process of progression, from previously differentiated neoplasms. A common genetic alteration in thyroid tumors is the rearrangement of the tyrosine kinase-encoding RET proto-oncogene, leading to the generation of chimeric RET/PTC oncogenes. To define the characteristics of the thyroid tumor subset with RET rearrangements, we have investigated its activation by a combined immunohistochemistry and reverse transcription-PCR approach in a series of 316 well-characterized thyroid tumors representative of the main diagnostic groups. RET activation was detected in 81 of 201 (40.3%) papillary carcinomas. It correlated with tumors exhibiting the "classic" morphological features of papillary cancer or with the microcarcinoma subtype (P = 0.017). RET activation in papillary carcinoma was not associated with clinical markers (such as large tumor size, extrathyroidal extension, or metastases) of increased morbidity. Follicular-type neoplasms (61 adenomas and 22 carcinomas), as well as the aggressive poorly differentiated (15 cases) or undifferentiated (anaplastic) carcinomas (17 cases), were negative. This study demonstrates that all thyroid carcinomas harboring activating RET rearrangements exhibit a well-differentiated phenotype, that of papillary carcinoma, and indicates that the subset of RET/PTC-positive papillary carcinomas do not progress to more aggressive, less differentiated tumor phenotypes.
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PMID:RET/PTC oncogene activation defines a subset of papillary thyroid carcinomas lacking evidence of progression to poorly differentiated or undifferentiated tumor phenotypes. 1058 93

The papillary carcinoma family (PCF) of thyroid tumors includes a wide variety of neoplastic entities regarded as well-differentiated, poorly differentiated, and undifferentiated papillary thyroid carcinomas. Recent studies have established the presence of alternative oncogenic rearrangements of the RET and NTRK1 genes in a consistent fraction (< or = 50%) of papillary thyroid tumors. RET oncogenic rearrangements are also very frequent (approximately 60%) in Chernobyl radiation-associated papillary thyroid neoplasias, which show an increased aggressiveness in terms of pathological stage at disease onset. These observations prompted us to study the relationship between the presence or absence of RET and NTRK1 oncogenes and the clinicopathological features (age, sex, histopathology, and pTNMC2 staging) of 76 consecutive, non-radiation-related tumors of the PCF. As previously reported, statistical univariate analysis revealed a correlation between the combination of RET and NTRK1 (RET/NTRK1) positivity and young age of patients at diagnosis. In addition, a significant association was found between RET/NTRK1 positivity and locally advanced stage of disease at presentation (pT4: P < 0.015). The multivariate analysis confirmed that RET/NTRK1 activation parallels an unfavorable disease presentation, which may correlate with a less favorable disease outcome. Furthermore, within the PCF, the frequency of RET/NTRK1 positivity was not influenced by the different neoplastic subtypes or the tumor versus degree of differentiation.
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PMID:RET/NTRK1 rearrangements in thyroid gland tumors of the papillary carcinoma family: correlation with clinicopathological features. 951 75

It has now been clearly established that quantitative immunohistochemical methods applied to tumour angiogenesis under suitable quality control conditions are a powerful prognostic tool for use in the initial assessment of breast carcinomas. Appropriate parameters for predicting the aggressiveness of tumours and their sensitivity to treatment are, however, still required. To determine whether the microvessel count (MVC) may serve to predict the chemotherapeutic response, a retrospective study was carried out on a series of 162 patients with breast carcinoma, who were all treated with the same standard adjuvant chemotherapy. Angiogenesis was assessed by performing CD31 immunostaining and MVC per mm2. Several other factors such as P53, ERBB2, BCL2, and Ki67 were also measured, and their prognostic value was compared with that of the MVC. The MVC was not found to be correlated with any of the other prognostic parameters, but turned out to be of great prognostic value whatever the threshold value chosen, which suggests that it is continuously valid at all levels. The median value of the MVC (43.5 per mm2) divided this series into two significantly different prognostic categories, in terms of both disease-free survival (P = 0.0002) and overall survival (P = 0.037). Univariate analysis showed that most of the parameters analysed were of prognostic value regarding the disease-free survival, namely grade (P = 0.029), mitotic index (P = 0.049), size (P = 0.015), oestrogen receptors (P = 0.022), progesterone receptors (P = 0.018), P53 (P = 0.0045), ERBB2 (P = 0.046), and Ki67 (P = 0.0008). As regards overall survival, grade and ERBB2 showed a loss of prognostic value. In multivariate analysis on disease-free survival, the MVC was the most accurate prognostic factor (RR = 2.64), followed by Ki67 (RR = 2.06) and P53 (RR = 1.69). With respect to overall survival, the MVC ranked third among the prognostic parameters analysed. Standard chemotherapy did not reduce the high prognostic value of the MVC performed on tumour angiogenesis. This suggests that the MVC may predict the degree of resistance to chemotherapy. Patients with high levels of angiogenesis, particularly node-negative patients, might therefore be able to benefit from adjuvant therapy of another kind.
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PMID:Angiogenesis as a prognostic marker in breast carcinoma with conventional adjuvant chemotherapy: a multiparametric and immunohistochemical analysis. 960


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