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)

A retrospective analysis of 600 patients treated for head and neck malignancy at the Cooper Hospital/University Medical Center was undertaken. Patients who had surgical intervention (excluding biopsy) were withdrawn from this review. Fifty-eight patients with Stage I Glottic Laryngeal Carcinoma were identified and constitute the basis of this report. Various parameters were analyzed to assess their impact on local control. These include age, sex, serum hemoglobin, tumor bulk, differentiation, field size, total dose, total treatment time, and fraction size. Overall local control was 87% with a median follow-up of 63 months. The only factor that influenced local control was fraction size. Of 28 patients treated with 180 cGy fractions, seven (25%) had a local recurrence within 3 years. Twenty-eight patients treated with 200 cGy or greater fractions have had no failures to date. The difference in control rate when comparing the two treatment schema was significant (p less than 0.01). The median dose in the controlled 180 cGy group was 6660 cGy (range, 6300-7020 cGy). In the patients who failed in the 180 cGy group the median dose was 6660 cGy (range, 6480-6840 cGy). The patients receiving 200 cGy fractions or greater had a median dose of 6600 cGy (range, 6000-6950 cGy) and an average dose of 6507 cGy. The mean NSD in the 180 cGy group failing was 1787 RET (range, 1735-1843 RET). Patients who were controlled and received 180 cGy fractions had a median NSD of 1796 RET (range, 1743-1868). The mean NSD in the 200 cGy group was 1847 RET. The median TDF in the 180 cGy group of patients controlled was 102. Those failing also had a TDF of 102 (range, 101-105). Patients receiving 200 cGy fractions or greater had a median TDF of 109. It appears from this data that fraction size is a highly significant factor in our ability to control glottic laryngeal cancer.
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PMID:The effect of fraction size on control of early glottic cancer. 334 52

The property of methandrostenolone, a synthetic male hormone, as a stimulator of proliferative activity of tumour cells was studied in experimental analyses, conducted on the transplanted culture of HEP-2 cells and on xenografts of the human larynx cancer cultured in diffusive chambers. This property of the hormone was used to increase the sensitivity of human laryngeal tumour, to ionizing emission. The morphological study of histological specimens prepared from xenografts and histological specimens of patients with laryngeal tumour, who received preoperative distant gamma-therapy against a background of the methadrostenolone use, gave the results which allow recommending this hormone to be used during radiotherapy of patients with the laryngeal cancer.
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PMID:[Radiomodifying effect of methandrostenolone on laryngeal cancer cells]. 358 42

The expression of EGF/EGFR in 47 laryngeal surgical specimens from 44 patients was examined. PCNA analysis as an index of proliferating cells was also performed in 32 cases of laryngeal cancer, six cases of pre-cancerous lesions and nine cases of normal laryngeal mucosa. EGFR failed to show a significant correlation with tumour behaviour, but EGF expression was statistically significantly higher in malignant (SCC) than in non-malignant tissues (pre-cancerous and normal tissues) (p < 0.006), and PCNA also showed a statistically significant difference (p < 0.016) between the two. In malignant tissues when EGF/EGFR in 'double-positive' and 'double-negative' cases was compared, a statistically significant difference in PCNA was found (p < 0.029); but this was not seen in non-malignant tissues. Our results support the hypothesis that an autocrime mechanism exists in laryngeal cancer and in this mechanism EGF may play an important role in tumour progression, especially when EGFR is overexpressed.
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PMID:Expression of EGF, EGFR and PCNA in laryngeal lesions. 756 70

The effect of human on PCNA expressions of HEP-2 lines was investigated using LSAB (Labelled streptacidin biotin method) with monoclonal antibody Ki-67 (anti-PCNA). The results showed that the PCNA expression which reflects the proliferative activity of cells was dependent on dose of rhu-IFN-gamma in HEP-2 cell lines. Thus, our data suggest that rhu-IFN-gamma might be useful in the treatment of laryngeal cancer because it provides effective cytostatic.
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PMID:[Effect of human recombinant gamma-interferon on proliferative activity of human laryngeal cancer cell lines]. 964 84

The function of VEGF in laryngeal carcinoma was studied by observing either the expressions of VEGF and its receptor flk-1 in laryngeal carcinoma, or the effect of anti-VEGF antibody and anti-VEGF receptor antibody on the growth of human laryngeal cancer cell line HEP-2 in vitro. The expression of VEGF and flt in the specimen of laryngeal carcinoma were determined by standardized immunohistochemistry (Elite ABC method). Anti-VEGF antibody and anti-VEGF receptor antibody were also added at various concentrations to the culture medium, respectively, and the growth of HEP-2 was measured by MTT assay. The immunohistochemical staining showed that the expressions of VEGF and flt were detected both in carcinoma cells and endothelial cells. The growth of HEP-2 cell line in vitro was suppressed when adding various concentration of anti-VEGF antibody and anti-VEGF receptor antibody to the culture medium. The laryngeal cancer cells can secret VEGF and there exists VEGF-binding site on laryngeal cancer cell. Both blockading VEGF with anti-VEGF antibody and blockading VEGF-binding site with anti-VEGF receptor antibody could inhibit HEP-2 growth.
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PMID:[The influence of vascular endothelial growth factor and its receptor on the growth of laryngeal cancer cell]. 1126 58

This study aimed to explore the molecular mechanism in tumor invasion and metastasis. The expression of matrix metalloproteinase-2, -9 (MMP-2, MMP-9), tissue inhibitor-1 of matrix metalloproteinase (TIMP-1), cell adhesion molecule 44 variant 6 (CD44v6), HER2/neu and p53 was investigated in 154 patients with head and neck squamous cell carcinoma (SCC) by ABC and ImmunoMax immunohistochemical method. Their clinical relevance and correlation were analysed. The expression of MMP-2, MMP-9, TIMP-1, CD44v6, HER2/neu and p53 was found in cancer cells in 87.01%, 85.71%, 68.18%, 98.05%, 55.19% and 50.65% cases respectively. Linear regression and correlation analysis revealed that there was close positive relationship (P<0.05) between the expression of MMP-2 and MMP-9, TIMP-1 and CD44v6, HER2/neu and MMP-9, MMP-2 and p53. Up-regulation of MMP-2 was accompanied by advanced T stage (P<0.01). There was also a trend of MMP-2 expression being related with tumor metastasis. Increased expression of HER2/neu was found in patients with tumor recurrence(P<0.05). The expression of TIMP-1 was higher in laryngeal cancer than that in pharyngeal cancer, and higher in keratinizing and non-keratinizing SCC than that in basaloid SCC(P<0.05). These findings suggested that MMP-2 and MMP-9, HER2/neu and MMP-9, MMP-2 and p53 had a coordinate function in aggression of tumor; that MMP-2 had a more important function than MMP-9 in tumor invasion and metastasis; and that HER2/neu might serve as a biomarker for poor prognosis in HNSCC.
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PMID:Correlation of matrix metalloproteinase-2, -9, tissue inhibitor-1 of matrix metalloproteinase and CD44 variant 6 in head and neck cancer metastasis. 1286 29

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

Judging from recent data, heritable forms account for 30-40% of pheochromocytomas. The molecular basis for the familial pheochromocytoma has been largely elucidated and the role of germline mutation of the VHL, RET, SDHB, and SDHD genes has been established. However, on genotyping a group of 172 sporadic or familial pheochromocytomas, we characterized four unrelated probands with familial pheochromocytomas without any sequence variants of RET (exons 8, 10, 11, 13, 14, 15, and 16) or the entire coding sequence of VHL, SDHB, SDHC, SDHD, and EGLN3 (exon-intron boundaries included). The proband of family 1 is a man who had a bilateral pheochromocytoma at the age of 32 and a local recurrence at the age of 48 years. His brother died of malignant pheochromocytoma and his nephew died suddenly of an undiagnosed pheochromocytoma. The proband of family 2 is a female who had a 5-cm benign adrenal pheochromocytoma at the age of 34 years, while her cousin (maternal branch) had a monolateral pheochromocytoma at the age of 42 years. No other tumors had been reported in either family. The proband of family 3 is a female who had a bilateral pheochromocytoma at the age of 66 years. Her sister had a bilateral pheochromocytoma and breast cancer at the age of 54 years. Several other tumors were recorded in this family, including laryngeal cancer, leukemia, and a case of medullary thyroid carcinoma (MTC) in one brother. MTC was naturally ruled out in the proband and her sister. In family 4, the proband was a female who had a bilateral pheochromocytoma at the age of 46 years and a local recurrence a few years later, with liver metastases from the pheochromocytoma. Her brother had a monolateral benign pheochromocytoma. The proband also had a melanoma and bilateral renal cysts. This case revealed a VHL sequence variant IVS2+43 A>G, which was also found in one other unrelated sporadic pheochromocytoma. VHL mRNA integrity is currently being evaluated. The proband had no cerebellar or spinal NMR findings or retinal alterations. In family 5, the proband was a female who had a right adrenal pheochromocytoma at the age of 50 years and a breast cancer at 49 years of age. Her mother had had a right adrenal pheochromocytoma at 61 years of age. Although other molecular mechanisms, such as particular variants in untranslated regions or partial gene deletions, cannot be ruled out, we think finding families with nonsyndromic pheochromocytoma without any RET, VHL, SDHB, SDHC, SDHD, or EGLN3 mutation may argue in favor of the presence of other pheochromocytoma susceptibility genes.
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PMID:Familial nonsyndromic pheochromocytoma. 1710 81

Sulindac has antineoplastic effects on various cancer cell lines; consequently, we assessed sulindac's effects on laryngeal squamous cell carcinoma (SCC) cells in vitro and in vivo. In vitro, SCC (HEP-2) cells treated with various cyclooxygenase inhibitors or transfected with constitutively active signal transducer and activator of transcription 3 (Stat3) or survivin vectors were analyzed using Western blot analysis, annexin V assay, and cell proliferation assay. In parallel, nude mice injected subcutaneously with HEP-2 cells were either treated intraperitoneally with sulindac or left untreated, and analyzed for tumor weight, survivin expression, and tyrosine-phosphorylated Stat3 expression. In vitro studies confirmed the selective antiproliferative and proapoptotic effects of sulindac, which also downregulated Stat3 and survivin protein expression. Stat3 or survivin forced expression partially rescued the antiproliferative effects of sulindac. In vivo studies showed significant repression of HEP-2 xenograft growth in sulindactreated mice versus controls, with near-complete resolution at 10 days. Additionally, tumor specimens treated with sulindac showed downregulation of phosphorylated tyrosine-705 Stat3 and survivin expression. Taken together, our data suggest, for the first time, a specific inhibitory effect of sulindac on tumor growth and survivin expression in laryngeal cancer, both in vitro and in vivo, in a Stat3-dependent manner, suggesting a novel therapeutic approach to head and neck cancer.
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PMID:Sulindac induces apoptosis and inhibits tumor growth in vivo in head and neck squamous cell carcinoma. 1740 59

Despite abundant literature on the use of PET in head and neck cancer, a little is known about the visualization of small laryngeal cancer. Moreover, most literature deals with the radiopharmaceutical (18)F-fludeoxyglucose (FDG), whereas only a few papers address the use of (11)C labeled amino acids. This study was performed to evaluate the feasibility of (11)C-labeled methionine in visualizing small laryngeal cancer. Ten patients with a de novo small laryngeal cancer (7 T1, 3 T2) underwent a MET PET at least 3 weeks after biopsy but prior to further treatment. Static scans were made in 'whole body' mode, covering the head from the external auditory meatus downwards to the whole thorax. The resulting images were judged by experienced specialists in nuclear medicine, who assessed the relative visibility of each tumor on a 3-point scale. Nine tumors were visualized (5 clearly, 4 moderately). One (T1) was not visualized. Small laryngeal cancer can be visualized with (11)C-methionine PET.
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PMID:Visualization of small glottic laryngeal cancer using methyl-labeled 11C-methionine positron emission tomography. 1914 93


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