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)

We analyzed the alteration of int-2, c-erbB-2 and EGFR genes in 32 cases of transitional cell carcinoma of the urinary tract, 15 cases of renal cell carcinoma and 14 cases of prostatic carcinoma by Southern blot hybridization method. Three- to 12 fold amplification of int-2 gene was observed in 4 (12.5%) of 32 transitional cell carcinomas. Of these 4 cases 3 were G3 tumor with muscle invasion and the remaining was G1, pTa tumor with subsequent recurrence of multiple tumors. The other 2 cases (6.3%) with invasive transitional cell carcinoma showed amplification of c-erbB-2 gene. Neither amplification nor gross rearrangement of EGFR gene was detected in transitional cell carcinoma. On the other hand, renal cell carcinomas and prostatic carcinomas had neither amplification nor gross rearrangement of these 3 genes. These results suggest that the int-2 gene located in chromosome locus 11q13 and the c-erbB-2 gene have a specific role in carcinogenesis and in progression of transitional cell carcinoma through their gene amplifications.
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PMID:[int-2 and c-erbB-2 gene amplification in urological cancers]. 136 54

Cell kinetic data are an important adjunct to histologically based tumor classifications and provide reliable information about future tumor behaviour. The growth fraction of 62 transitional cell carcinomas was assessed using Ki-67 and PCNA (Proliferating cell nuclear antigen/cyclin) immunostainings. Ki-67 recognises an unknown nuclear antigen expressed in dividing cells and requires the use of frozen sections. PCNA, a non histone nuclear protein, identifies proliferating cells within fixed, embedded tissue sections. The percentage of labeled cells was expressed as the labeling index (LI). The median LI in normal urothelium and transitional cell carcinoma were 0.5% and 8%, respectively for Ki-67, and 1.5% and 12% for PCNA. A general agreement between indices of cell proliferation and histological grade and stage was demonstrated. Although some discrepancies were observed, there was a strong correlation between Ki-67 and PCNA Lis (r = 0.8308, P < 0.01). In addition, tumor EGFR positive had PCNA values greater than those found in cancer EGFR negative (P = 0.01). These findings suggest that immunohistochemical nuclear labeling with anti-PCNA on routinely processed tissue is a simple technique for the assessment of transitional cell carcinomas.
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PMID:PCNA/cyclin expression in transitional cell carcinomas of the human bladder: its correlation with Ki-67 and epidermal growth factor receptor immunostainings. 793 59

The bladder transitional cell carcinoma cell line, BTT739 from the T739 mouse, was transfected with a plasmid that encoded an enhanced green fluorescence protein (GFP) and the cells stably expressing GFP were selected and subcloned. 1 x 10(3)-1 x 10(4) GFP-labeled BTT739 cells were injected under the skin of ear of T739 mice. On day 2-5 post injection, the most interesting manifestations observed were the chemotaxis-like movement of the tumor cells toward the pre-existing host vasculature, host vessel dilation and tortuosity and increased extravasation. On day 10 or later, the sprout from pre-existing host vasculature was observed. Once angiogenesis was triggered on, the tumor cells grew more rapidly and exhibited a specific growth pattern where tumor cells always associated with or surrounded the vessels. The newly formed microvessels always showed heavy extravasation. Immunohistochemistry staining revealed strong VEGF and VEGFR2 (Flk-1) expression in tumor cells. Angiography using Rhodamin-labeled dextran showed neovascularization with unprecedented clarity. However, the tumor mass, even bigger than 2 mm and being neovascularized, shrunk and then disappear in 3-5 days and left only delicated host vessels and recovered extravasation. The evidence from this observation indicated that angiogenesis induced by tumor cells after implantation into the host begins at very early stage. The micrometastases foci could not form or survive without vigorous and continuous angiogenesis. Furthermore, there was active VEGF paracrine and autocrine expression in tumor and high level VEGF secretion by tumor cells plays an important role in initiating angiogenesis and supporting micrometastases.
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PMID:[A novel model for visualization of tumor cell-induced angiogenesis in vivo]. 1195 29

The improved understanding of the molecular biology of urothelial malignancies is helping to define the role of new targets and prognostic indices that can direct the most appropriate choice of treatment for advanced disease. Many human tumors express high levels of growth factors and their receptors that can be used as potential therapeutical targets. Tyrosine-kinase receptors, including many growth factor receptors such the receptors for epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and Her2/neu, have been found overexpressed in urothelial tumors. For many of these growth factor receptors, the degree of expression has been associated with the progression of cancer and a poor prognosis. Among the best studied growth factor receptors are the two members of EGF receptor familiy EGFr (ErbB-1), and Her2/neu (ErbB-2). Several preclinical studies in bladder cancer models, have confirmed that systemic administration of growth factor inhibitors inhibits the growth and metastasis of human transitional cell carcinoma established in the bladder wall of athymic nude mice. Additional studies indicate that therapy with EGFR inhibitors enhances the activity of conventional cytoreductive chemotherapeutic agents, in part by inhibiting tumor cell proliferation, angiogenesis, and inducing apoptosis. Novel targeted therapy hold promise to improve the current results of bladder cancer treatment. Based on the success seen with anti-HER2 monoclonal antibodies (Herceptin) and the promising results with EGFR targeted agents (IMC-C225 Cetuximab, ZD1389 Iressa, OSI-774 Tarceva, GW 57016) in other tumor types, and based on the results obtained in preclinical models, there is a great interest in assessing these agents in patients with bladder cancer. Several trials are now ongoing testing these new agents alone or in combination with chemotherapy in bladder cancer patients. The integration of these newer biologic agents, probably to supplement rather than to supplant chemotherapeutic drugs, should be a primary direction of research with the objective to interfere with multiple aspects of bladder cancer progression. However, the value of integration of biologically targeted agents into combined modality treatment for patients with bladder cancer has still to be proven.
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PMID:Novel approaches with targeted therapies in bladder cancer. Therapy of bladder cancer by blockade of the epidermal growth factor receptor family. 1285 May 30

The mortality from transitional cell carcinoma (TCC) of the urinary bladder increases significantly with the progression of superficial or locally invasive disease (pTa/pT1) to detrusor muscle-invasive disease (pT2+). The most common prognostic markers in clinical use are tumour stage and grade, which are subject to considerable intra- and interobserver variation. Polysomy 17 and HER2/neu gene amplification and protein overexpression have been associated with more advanced disease. Standardised techniques of fluorescence in situ hybridisation and immunohistochemistry, which are currently applied to other cancers with a view to offering anti-HER2/neu therapies, were applied to tumour pairs comprising pre- and postinvasive disease from 25 patients undergoing treatment for bladder cancer. In the preinvasive tumours, increased HER2/neu copy number was observed in 76% of cases and increased chromosome 17 copy number in 88% of cases, and in the postinvasive group these values were 92 and 96%, respectively (not significantly different P=0.09 and 0.07, respectively). HER2 gene amplification rates were 8% in both groups. Protein overexpression rates were 76 and 52%, respectively, in the pre- and postinvasive groups (P=0.06). These results suggest that HER2/neu abnormalities occur prior to and persist with the onset of muscle-invasive disease. Gene amplification is uncommon and other molecular mechanisms must account for the high rates of protein overexpression. Anti-HER2/neu therapy might be of use in the treatment of TCC.
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PMID:HER2/neu overexpression in the development of muscle-invasive transitional cell carcinoma of the bladder. 1452 Apr 64

Urothelial carcinoma (UC), the common histological subtype of bladder cancer, presents as a papillary tumor or as an invasive, often lethal form. To study UC molecular biology, candidate gene and genome-wide approaches have been followed. Here, it is argued that a 'cancer pathway' perspective is useful to integrate findings from both approaches. According to this view, papillary cancers typically exhibit activation of the MAPK pathway, as a consequence of oncogenic mutations in FGFR3 or HRAS, with increased Cyclin D1 expression. In contrast, invasive UC are characterized by severe disturbances in proximate cell cycle regulators, e.g. RB1 and CDKN2A/p16(INK4A), which decrease dependency on mitogenic signaling. In addition, these disturbances permit, promote and are in turn exacerbated by chromosomal instability, which is further enhanced by loss of TP53 function. In another vicious cycle, defective cell cycle regulation interacts with DNA methylation alterations. The transition toward invasive UC may require concomitant and interacting defects in cell cycle regulation and the control of genomic stability. Intriguingly, neither canonical WNT/beta-Catenin nor hedgehog signaling appear to play major roles in UC. This may reflect its origin from more differentiated urothelial cells possessing a high regenerative potential rather than a stem cell population.
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PMID:Understanding urothelial carcinoma through cancer pathways. 1655 69

A hospital-based case-control study was conducted near a former black-foot disease (BFD)-endemic area in southwestern Taiwan to examine the possible risk factors and genetic susceptibility for urinary transitional cell carcinoma (TCC). A total of 221 patients with pathologically confirmed TCC and 223 age-sex-matched control subjects from urology outpatient clinics were recruited between 1998 and 2002. The results showed that residency in the BFD area and consumption of well water for more than 10 years was a strong factor on urinary cancer risk (odds ratio [OR],8.16, 95% confidence interval [CI],3.34-19.90, p<0.0001). Dose response relationship between average arsenic concentration in well water and TCC risk was also observed. Cigarette smoking played a relatively minor role in urinary carcinogenesis in this study. The GSTP1 Ile105Val A-->G polymorphism was significantly associated with cancer risk (A/G+G/G: OR=0.60, 95%CI=0.39-0.94, p=0.02), and the effect of Val105 allele was largely confined to the subjects diagnosed earlier than 55 years old (A/G+G/G: OR,0.29; 95% CI, 0.09-0.87, p=0.03). The results suggest that GSTP1 is a candidate for susceptibility locus and Ile105 allele may predispose individuals to early-onset urinary TCC. The GSTM1 null genotype was associated with tumors of high-invasiveness (OR,2.21; 95% CI, 1.34-4.73) as well as with early-onset TCC risk (OR,2.53; 95% CI, 0.97-6.59). Our preliminary results showed the XRCC1 Arg194Trp were associated with arsenic-related urinary TCC and the interaction between the genotype and the exposure was statistically significant. The modulating effect of the GSTM1, GSTT1, GSTP1 Ile105Val, EPHX Tyr113His and XRCC1 Arg280His on arsenic-related TCC risk was also suggestive. These observations implied that impaired metabolism of carcinogenic exposure as well as impaired DNA repair function play an important role in arsenic-related urinary transitional cell carcinogenesis.
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PMID:SNPs of GSTM1, T1, P1, epoxide hydrolase and DNA repair enzyme XRCC1 and risk of urinary transitional cell carcinoma in southwestern Taiwan. 1819 64

Malignant lymphoma presenting in the bladder has been classified in primary cases, as the first sign of disseminated disease and as a secondary infiltration. Most of the examples in the literature have been reported as single cases. Reported herein is the case of a 45-year-old man with an anaplastic large cell lymphoma (anaplastic lymphoma kinase (ALK) and granzyme B positive) that presented as a bladder neoplasm. The morphological differential diagnosis was complex because the EMA-positive immunophenotype, CD45 and CD3 negativity and the clinical manifestation simulated a transitional cell carcinoma. It is important to be aware of its existence because a poorly differentiated bladder carcinoma cannot be ruled out if CD30 and ALK immunostaining are not performed. T-cell receptor-gamma clonal rearrangement could be also helpful in these cases. Although bladder involvement by recurrent lymphoma is a sign of widely disseminated disease and it is associated with a very poor prognosis, it seems that chemotherapeutic regimens in this kind of ALK-positive lymphoma could be effective, given that the present patient had an impressive response to chemotherapy treatment.
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PMID:Anaplastic lymphoma kinase-positive anaplastic large cell lymphoma presenting as a bladder neoplasm. 1832 19

This study investigates the potential clinical significance of c-erbB-2 gene and chromosome 17 alterations by fluorescence in situ hybridization (FISH) analysis and HER2/neu overexpression by immunohistochemical staining in transitional cell carcinoma (TCC) of urinary bladder correlating the results with tumor stage and grade categories and with clinical behavior. Sixty-three cases of TCC retrieved from the files of 2 institutions were analyzed for chromosome 17 aberrations and c-erbB-2 amplification by FISH analysis and evaluated immunohistochemically for HER2/neu overexpression. Five tumors were G1, 29 intermediate grade (G2), and 29 tumors high grade (G3); 32 tumors had stage Ta, 18 tumors T1, and 13 tumors T2. We found polysomy of chromosome 17 in 58.7% of TCC with average chromosome copy number >2.26; increased number of HER2/neu gene copy was observed in 66.7% of tumors. C-erbB-2 amplification occurred in 6.3% of tumors. Immunohistochemically, 60.3% of TCC overexpressed HER2/neu and 39.7% of tumors were negative. All tumors with polysomy showed simultaneously increase of HER2/neu gene copy number of which 34/37 with protein overexpression. A statistically significant correlation between polysomy of chromosome 17 and tumor stage (P = .0003) and tumor grade (P < .0001) was found; polysomy was not seen in G1 tumors; however, 8/29 G2 tumors and 29/29 G3 tumors revealed polysomy of chromosome 17; in 8/32 Ta tumors, 14/18 T1 and 13/13 of deeply invasive tumors (T2) polysomy 17 was observed. Moreover, it was found that 7 superficial tumors (1 Ta and 6 T1) showed high polysomy with average of chromosome 17 copy number > or =3.76 as observed in all invasive tumors. The data suggest that although HER2/neu amplification, found in high grade and invasive tumors, is a rare event in TCC, polysomy of chromosome 17 is an important factor correlated with tumor stage and grade categories and could be considered a molecular marker of tumor progression with interesting diagnostic implications.
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PMID:Role of polysomy 17 in transitional cell carcinoma of the bladder: immunohistochemical study of HER2/neu expression and fish analysis of c-erbB-2 gene and chromosome 17. 1944 84

The author reports a rare case of sarcomatoid carcinoma with an emphasis on immunohistochemical features. A 79-year-old man was admitted to our hospital because of hematuria. An endoscopy revealed a large polypoid tumor in the bladder, and urine cytology demonstrated malignant cells. A cystectomy was performed. The patient is now alive without metastasis 4 months after the operation. Grossly, a large polypoid tumor (5 x 6 x 5 cm) was present in the bladder. Microscopically, the tumor consisted of high-grade transitional cell carcinoma element (10% in area) and sarcomatoid element (90% in area). There was a gradual transition between the two. The tumor cells were invaded into peribladder tissue (pT3b). Immunohistochemically, the sarcomatoid element was positive for four types of pancytokeratins, high-molecular weight cytokeratin (CK), CK5/6, CK7, CK18, CK19, epithelial membrane antigen (EMA), vimentin, p53 protein, p63, Ki-67 (labeling = 92%), neuron-specific enolase (NSE), and platelet-derived growth factor receptor-alpha (PDGFRA). It was negative for CK14, CK20, melanosome, carcinoembryonic antigen (CEA), desmin, S100 protein, myoglobin, alpha-smooth muscle antigen (ASMA), CD34, chromogranin, synaptophysin, CD56, CD68, and KIT. The transitional cell carcinoma element showed similar immunoreactivity except for negative CK5/6, positive CK20, and negative vimentin. A molecular genetic analysis of KIT gene (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) gene with the use of PCR-direct sequencing showed no mutations. The present case is the first report of sarcomatoid carcinoma of the urinary bladder demonstrating extensive immunohistochemistry and mutational status of KIT and PDGFRA genes. The sarcomatoid carcinoma in the present case may be derived from sarcomatous differentiation of high-grade transitional cell carcinoma.
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PMID:Sarcomatoid carcinoma of the urinary bladder: a case report with immunohistochemical and molecular genetic analysis. 1952 96


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