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)

Reduced cellular immune response is well documented in patients with advanced breast cancer. To investigate immunocompetence at the time of diagnosis, 104 patients with breast cancer staged according to the TNM classification were studied preoperatively and compared with 95 age matched healthy women. Tests of blood mononuclear leukocytes included lymphocyte and monocyte counts, determination of rosette forming T (SER +) and B (MER +) lymphocytes, T lymphocyte subsets defined with monoclonal antibodies (Leu-1, Leu-2a, Leu-3a) and with lectin fractionation (soybean agglutinin, SBA), lymphocyte transformation tests with PHA and ConA and colony formation of T cells in agar (TL-CFC). Two age groups (A: 30-50, B: 51-70 years) and the different tumor stages (I-IV) were analyzed. Patients and controls did not differ in absolute numbers of lymphocytes, T and B cells. In patients of group B the absolute number of monocytes was slightly increased in stages II and III and significantly in stage IV (p less than 0.025). Similarly, the lymphocyte response to PHA was significantly reduced in stage IV group B only (p less than 0.05). ConA induced lymphocyte proliferation and TL-CFC capacity were not different in patients and controls. In the small number of patients and age matched controls, in whom T lymphocyte subsets were determined, the relative numbers of T cells with helper or suppressor phenotype as defined with Leu-3a, Leu-2a, or SBA were similar. In conclusion, in breast cancer, at the time of diagnosis, blood T lymphocyte populations and functions are not altered except in elderly patients with disseminated disease. The monocytosis and reduced PHA responsiveness observed in the latter group may be related phenomena.
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PMID:[Intact cellular immune response in patients with locally metastasizing breast carcinoma at the time of diagnosis]. 622 73

The present study attempts to clarify the specific contribution of cathepsin D (CD) and pS2 to the progression of breast cancer (BC) by examining the relationship between these two factors and TNM status, tumour grade, estradiol receptors (ER) and the prognosis factors epidermal growth factor receptor (EGFR) and neu amplification in a group of 270 BC patients. CD and pS2 were determined by an immunoradiometric procedure in tumour cytosols obtained for ER. Neu amplifications were evaluated by dot-blot, in tumour DNA. EGFR was determined in membrane tumour preparations obtained from ER cytosols by a two-point radiometric saturation assay. CD is basically related to bad prognosis factors and has a direct correlation with tumour size (P = 0.025) and EGFR content (P = 0.007) and is associated with the presence of metastases (P = 0.000). pS2 is mostly related to good prognosis factors and showed an inverse correlation with the Scarff-Bloom Index (P = 0.011) and a direct correlation with ER content (P = 0.014). Finally, pS2 and CD also showed a strong mutual association (P = 0.009) and the fact that both correlated with ER content confirms in tumours the experimental finding that they are estrogen-induced proteins.
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PMID:Specific oncological contribution of cathepsin D and pS2 in human breast cancer: their relationship with TNM status, estradiol receptors, epidermal growth factor receptor and neu amplification. 892 Feb 30

When mutations of the RETproto-oncogene were found in 1993 to account for hereditary medullary thyroid carcinoma (MTC), surgeons obtained the opportunity to operate on patients prophylactically (i. e., at a clinically asymptomatic stage). Whether this approach is justified, and, if so, when and to which extent surgery should be performed remained to be clarified. A questionnaire was sent to all surgical departments in Germany and Austria. All of the patients who fulfilled the following criteria were enrolled: (1) preoperatively proved RET mutation; (2) age </= 20 years, (3) clinically asymptomatic thyroid C cell disease; and (4) TNM classification pT0-1/pNX/pN0-1/M0. Seventy-five patients were identified, and fifteen mutations were detected in six codons. Two adolescents had unilateral pheochromocytomas as part of the multiple endocrine neoplasia II (MEN-II) syndrome. No hyperparathyroidism was noted. All patients underwent total thyroidectomy, and 57 patients went on to have lymph node dissection. Parathyroid glands were removed in 34 patients and autografted in 11. Histopathology revealed MTC in 46 patients (61%, youngest 4 years); C cell hyperplasia (CCH) only was detected in the other 29 patients. Three patients had lymph node metastases (LNMs) the youngest being age 14 years. Calcitonin levels were not useful for differentiating between CCH and MTC, but in all patients with LNMs at least the stimulated calcitonin levels were assayed. After surgery, five patients (6.7%) sustained permanent hypoparathyroidism, and one patient (1.3%) had a permanent unilateral recurrent nerve palsy. All but three patients (96%) were biochemically cured. In conclusion, prophylactic total thyroidectomy can be performed safely in experienced centers. We recommend prophylactic total thyroidectomy at age 6. Cervicocentral lymph node dissection should be included when calcitonin levels are elevated or if patients are older than 10 years. Bilateral lymph node dissection should be performed if LNMs are suspected or when patients with elevated calcitonin are older than 15 years.
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PMID:Prophylactic thyroidectomy in 75 children and adolescents with hereditary medullary thyroid carcinoma: German and Austrian experience. 960 92

The expression and coexpression of EGFR, c-erbB-2 and c-erbB-3 in 21 gastric cancers and 20 chronic gastritis was examined using immunohistochemistry on fresh frozen tissues considering clinicopathological variables. Generally, gastric cancer patients showed a higher incidence of EGFR, c-erbB-2 and d-erbB-3 overexpression than the group with chronic gastritis (81% and 43%; 38% and 45%; 35% and 20%, respectively), however, statistically significant differences were found only for EGFR expression (p = 0.01). No association between immunoreactivity of all growth factor receptors and the histopathological structure of gastric cancer was observed. EGFR and c-erbB-3 proteins were detected more frequently in patients with III/IV than in I/II of TNM stages, while c-erbB-2 overexpression was higher in I/II vs. III/IV stages. In chronic gastritis with intestinal metaplasia and or coexisting carcinoma lesions, a higher frequency of the expression of studied proteins was observed in comparison with chronic gastritis without those alternations; however, these differences were statistically insignificant. The percentage of positive cases with coexpression of two proteins was comparable in gastric cancer and chronic gastritis (33% and 35%) but the simultaneous expression of all three receptors was evident only in gastric cancer (19%). Our results indicate that at least one or two members of EGFR related receptors could appear in the early stages of gastric tumorigenesis. The enhancement of c-erbB-2 and c-erbB-3 reactivity seems to cooperate with EGFR activation in the gastric cancer development. Our results indicate the promotional rather than direct transformational role for EGFR supergene family in gastric carcinogenesis.
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PMID:Expression of epidermal growth factor receptor family proteins (EGFR, c-erbB-2 and c-erbB-3) in gastric cancer and chronic gastritis. 970 36

In hereditary medullary thyroid carcinoma (MTC), few genotype-phenotype correlations have been established. RET genotypes (exons 10, 11, 13, and 14) of 63 patients with hereditary MTC (from November 1994 to October 1999) were correlated with age at diagnosis, sex, the TNM system, and basal calcitonin levels. Mutations in exons 10, 11, 13, and 14 were demonstrated in 22% (14 of 63), 54% (34 of 63), 21% (13 of 63), and 3% (2 of 63). The median ages at diagnosis differed significantly (38, 27, 52, and 62 yr; P = 0.003). When grouped by cysteine codons (exons 10 and 11 vs. exons 13 and 14), this difference became even more evident (30 vs. 56 yr; P = 0.001). Apart from age at diagnosis, no other significant associations were noted. Based hereon, three MTC risk groups were devised according to genotype: a high risk group (codons 634 and 618) with the youngest ages of 3 and 7 yr at diagnosis; an intermediate risk group (codons 790, 620, and 611) with ages of 12, 34, and 42 yr; and a low risk group (codons 768 and 804) with ages of 47 and 60 yr, respectively. Age at diagnosis was unrelated to specific nucleotide and amino acid exchange within each codon. The current data demonstrate that there is a significant genotype-phenotype correlation, allowing for a more individualized approach to the timing and extent of prophylactic surgery.
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PMID:Genotype-phenotype correlations in hereditary medullary thyroid carcinoma: oncological features and biochemical properties. 1123 93

We have determined the frequency of 918 RET proto-oncogene mutations (ATG-->ACG) in primary MTC tumors and metastases and correlated the presence or absence of this mutation with the clinical outcome of patients suffering from sporadic medullary thyroid carcinoma (MTC). A total of 197 samples, consisting of both primary tumors and lymph node metastases from 34 patients with sporadic MTC, were collected for PCR analysis of the RET 918 mutation. In 75 of the samples (38%), codon 918 (ATG-->ACG) mutations could be detected. The mutations showed a heterogeneous distribution: 21/34 patients (62%) had mutations in at least 1 tumor sample, and in 13 patients (38%) the mutation was present in all examined samples. Patients were considered 918mt when at least 1 tumor sample showed the RET 918 mutation. These 918mt and 918 wild-type (918wt) patients did not differ significantly concerning sex, age at diagnosis, TNM stage at diagnosis, number of examined tumor samples or follow-up time. However, 918mt patients showed more aggressive development of distant metastases during follow-up (p = 0.032, Fisher's exact test) with decreased metastases-free survival (p < 0.005, log-rank test). Furthermore, 918mt patients had a significantly lower survival rate than 918wt patients (p = 0.048, log-rank test). These data show that the RET codon 918 mutation has a prognostic impact on patients with sporadic MTC which may influence follow-up treatment.
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PMID:Prognostic value of codon 918 (ATG-->ACG) RET proto-oncogene mutations in sporadic medullary thyroid carcinoma. 1124 13

Small-cell lung cancer (SCLC) carries a bad prognosis despite good initial response to chemotherapy. It is therefore important to identify molecular markers that influence survival as potential new therapeutic targets. In our study, expression of the tyrosine kinase c-erbB-2 (HER2/neu) receptor in tumor tissues of 107 consecutive newly diagnosed patients with primary SCLC was quantified using a monoclonal antibody directed against the c-terminal domain of c-erbB-2. A clear-cut positive expression of c-erbB-2 was observed in 13% of patients. Surprisingly, c-erbB-2 was an independent prognostic factor (RR = 2.16; p = 0.014) when a proportional-hazard model was adjusted to stage (limited vs. extensive disease) and performance status (WHO I-IV), the most relevant clinical parameters. Similarly, a significant association between c-erbB-2 and survival was obtained if a larger number of clinical parameters were included into the analysis, namely response to chemotherapy, TNM stage, lactate dehydrogenase (LDH), neuron-specific enolase (NSE), gender and age (p = 0.033). Interestingly, c-erbB-2 expression was more relevant for patients with advanced tumors. In the subgroup of patients with bad performance status (WHO II-IV), median survival of patients with undetectable c-erbB-2 expression was 274 days compared with only 23 days for patients with clear-cut positive c-erbB-2 immunohistochemistry (p = 0.0031; log-rank test). Similar results were obtained for patients with extensive disease (p = 0.028) and high TNM stages (T>2 or N>1 or M1; p < 0.068, all comparisons). In contrast, c-erbB-2 expression was not associated with survival in patients with limited disease (p = 0.97), low TNM stages (p > 0.56, all comparisons) and good performance status (p = 0.97). In conclusion, c-erbB-2 is expressed in more than 10% of SCLC. Expression of c-erbB-2 is an independent prognostic factor of survival. The effect of c-erbB-2 expression seems to become more important in advanced stages of the disease. Since c-erbB-2 is a therapeutical target in other types of cancer, further studies to identify the role of c-erbB-2 in SCLC are clearly warranted.
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PMID:c-erbB-2 expression in small-cell lung cancer is associated with poor prognosis. 1130 79

Axillary lymph node status continues to be the single most important prognostic variable for breast cancer survival despite significant progress in the molecular and genetic characterization of breast malignancies. All patients with invasive breast cancer who underwent axillary lymph node dissection as part of their treatment were evaluated by 11 clinical and pathologic factors, including the primary lesion's T category (TNM staging system), whether the lesion was clinically palpable, the presence of lymphatic or vascular invasion, nuclear grade, estrogen and progesterone receptors, S-phase, age, HER2/neu overexpression, histology (infiltrating lobular or ductal), and ploidy. A total of 2282 axillary dissections were performed: 391 in patients with ductal carcinoma in situ (DCIS) [3 of which (0.8%) contained metastases] and 1891 in patients with invasive breast cancer [680 of which (36%) contained metastases]. Multivariate analysis of patients with invasive cancer identified four factors as independent predictors of axillary lymph node metastases: lymph/vascular invasion, tumor size, nuclear grade, tumor palpability. Among a group of 189 patients with nonpalpable, non-high-grade invasive lesions 15 mm or smaller without lymph/vascular invasion, only 6 (3%) had metastases to lymph nodes. If any three of the favorable factors were present, lymph node positivity was 6% or less. Clinical and pathologic feature of the primary lesions can be used to estimate the risk of axillary lymph node metastases. Such risk assessment can be used for the treatment decision-making process.
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PMID:Predicting axillary nodal positivity in 2282 patients with breast carcinoma. 1137 14

The most recent clinical studies are increasingly concerned about the molecular factors in terms of prognosis, predictivity of response to treatments and development of novel, targeted therapeutic strategies. An integrated diagnostic and prognostic approach is envisaged where molecular biology with the study of biological markers "integrates" TNM to enhance the control of primary disease, resulting in a prolonged disease-free overall survival, earlier and effective control of locoregional progression and better quality of life (organ and function preservation). The prognostic or predictive role of the response to treatment for some markers (p53, EGFR, cyclin D1, telomerase activity) is defined in part in head and neck tumors. More statistically relevant data are necessary to establish which of these factors can permit a better selection of candidates for more aggressive or molecular targeted therapies or for a closer follow-up, thus contributing to the change of the natural history of these tumors.
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PMID:Biological factors and therapeutic modulation in radiotherapy of head and neck cancer. 1269 48

Many factors affect the prognosis in operable laryngeal squamous cell carcinoma (LSCC). Many clinical factors have been implicated in tumor recurrence and poor survival of the patients. The aim of the present study is to investigate the demographic, clinical and histological characteristics as prognostic factors. Moreover, our aim is to analyze the role of modern molecular biomarkers in the prognosis of patients with LSCC. One hundred patients with operable laryngeal carcinoma underwent surgery as primary treatment between April 1999 and April 2002. Ninety-four of them were men and 6 women, with a median age of 62 years (39-77). All demographic data of the patients were recorded. Staging of the tumor revealed 20 cases with T2 cancer, 46 cases with T3 and 34 cases with T4, while N classification included 91 patients with N0 tumor, 3 with N1 and 6 with N2. Among the 100 cases, 47 were located in the glottis, 46 in the supraglottic region and 7 were transglottic. Histology grading revealed 35 cases of grade G1, 50 cases of G2 and 15 cases of G3. Postoperatively, all patients were followed regularly for the possibility of tumor relapse, with a median follow-up period of 40.2 months (4.8-58.4). During the operation, a tissue specimen was collected from the tumor. The specimens were used for RNA and DNA extraction. Isolated RNA was used to investigate the expression of wt-p53, bcl-2, VEGF and EGFR by the reverse transcriptase PCR method (RT-PCR) using specific primers, while genomic DNA was used for the detection of EBV and HPV (16/18 subtypes) by the consensus primer-mediated polymerase chain reaction method (PCR). All data such as tumor recurrence and survival were recorded. Statistical analysis was performed using the SPSS and STATA statistical packages in order to investigate the role of all clinical and molecular factors and their combinations as significant prognostic markers. The tumor recurrence rate was 31%, while the tumor associated death rate was 27% and total death rate 30%. Univariate analysis for overall survival showed significance for the T stage, TNM stage and site of the tumor. Univariate analysis for the time to progression showed significance for the T stage, N stage, TNM stage, site of the tumor and tumors simultaneously positive for EGFR and VEGF, while EGFR expression was borderline insignificant. Multivariate analysis revealed TNM stage as the only significant factor for overall survival, and TNM stage, site of the tumor and EGFR expression as significant factors for time to progression. The molecular biomarkers EGFR and VEGF have a prognostic significance in laryngeal cancer in addition to the established clinical prognostic factors such as the stage and site of the tumor. These markers, apart from their role in carcinogenesis, seem to play an important role in tumor relapse.
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PMID:Clinical and molecular prognostic factors in operable laryngeal cancer. 1573 81


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