Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Positron emission tomography studies on malignant head and neck tumors have shown that tumor growth and elevated glucose uptake are associated. On a molecular level, glucose uptake is mediated by specific glucose transport proteins, which exhibit an altered expression in head and neck malignant neoplasms. However, it is unknown when during development of squamous cell carcinomas an alteration of the expression of glucose transport proteins occurs. We have studied the expression of different facilitating glucose transport proteins (GLUT 1, 2, 3 and 4) by immunohistochemistry in a variety of preneoplastic and neoplastic mucosal lesions of the head and neck. We have observed weak expression of GLUT 1 in normal mucosa, a marked expression of GLUT 1 throughout preneoplastic lesions, which correlated well with the degree of dysplasia. In squamous cell carcinomas of the head and neck (HNSCC) and metastases, GLUT 1 was always expressed strongly. In contrast, GLUT 2, 3 and 4 were not detected in any of the epithelial tissues examined. The increased expression of GLUT 1 in dysplastic lesions and its sustained expression in SCC indicate that changes of GLUT 1 expression are early events during development of HNSCC. Therefore, the detection of GLUT 1 might be a reliable marker in the diagnosis of premalignant lesions of the oropharyngeal mucosa.
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PMID:Expression of facilitative glucose transport proteins during development of squamous cell carcinomas of the head and neck. 993 99

Transforming growth factor-beta (TGF-beta) and interleukin 10 (Il-10) are cytokines that have a strong immunosuppressive ability. Their secretion by tumor cells is able to suppress an immunological response against tumor. Both factors have been shown to enhance tumor growth in glioblastomas and carcinoma of the breast. We determined the expression pattern of TGF-beta and Il-10 in squamous cell carcinomas of the head and neck (HNSCC) and a possible association with tumor stage and their pre-treatment cytokine serum levels. Cytokine expression in primary tumors and metastases of 21 patients with HNSCC was investigated by immunohistochemistry. To assess the TGF-beta2 and Il-10 levels in tumor patients before therapy 49 serum specimens were analyzed by ELISA. TGF-beta2 was detected in 95% of all tumor tissues analyzed and Il-10 in 79% of all tumors. TGF-beta2 was localized in tumor cells and tumor borders, while Il-10 was preferentially found in peritumoral connective tissue. Metastasizing tumors showed elevated pretreatment serum levels for TGF-beta2 and Il-10. There was no correlation between TGF-beta2 and Il-10 expression in tumor tissue and pretreatment serum levels. Our data show that the majority of HNSCC analyzed express TGF-beta2 and Il-10. A correlation between pretherapy elevated cytokine serum levels and tumor grade was shown.
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PMID:[Cytokine expression of transforming growth factor-beta2 and interleukin-10 in squamous cell carcinomas of the head and neck. Comparison of tissue expression and serum levels]. 1055 Mar 71

Although clonogenic or divisional death is the main mechanism by which DNA-damaging agents demonstrate antitumor activity, recent data indicate that strategies specifically designed to trigger apoptosis may also prove to be useful antitumor agents. Protein kinase C (PKC) isoenzymes are involved in the regulation of cell proliferation, differentiation, and survival. Whereas pharmacological inhibition of PKC activity triggers apoptosis in most mammalian cells, cell line and tissue differences in sensitivities to these inhibitors remain. Whereas PKC inhibitors have potential as antitumor agents, issue of kinase specificity and solubility have remained obstacles to their clinical use. In this report, we investigated the antitumor activity of the PKC inhibitor chelerythrine chloride (chelerythrine), a selective inhibitor of group A and B PKC isoforms. Chelerythrine exhibited cytotoxic activity against nine human tumor cell lines tested in vitro. On the basis of the finding that radioresistant and chemoresistant squamous cell carcinoma lines (HNSCC) undergo apoptosis rapidly after treatment with chelerythrine in vitro, we assessed the effects of this agent on p53-deficient SQ-20B HNSCC cells in vivo. The results demonstrate that chelerythrine treatment of nude mice bearing SQ-20B is associated with significant tumor growth delay. Significantly, treatment with chelerythrine resulted in minimal toxicity. These findings demonstrate a potential for chelerythrine as an antitumor drug against squamous cell carcinoma.
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PMID:In vitro and in vivo activity of protein kinase C inhibitor chelerythrine chloride induces tumor cell toxicity and growth delay in vivo. 1069 May 61

MMP-9, which degrades extracellular matrix, is believed to play a crucial role in tumor invasion and metastasis. Angiogenesis is also perceived as an important step in tumor growth and metastasis. The aim of this study was to investigate the expression of MMP-9 in tumor samples of HNSCC patients and to study a possible correlation to angiogenic markers. Cryostat sections of 52 HNSCC tumors were immunostained for MMP-9, bFGF and VEGF using a standard streptavidin-biotin complex procedure for light microscopic investigation. Microvessel density (MVD) was determined by staining of endothelial cells immunohistochemically using anti-vWF monoclonal antibody. MMP-9 positive staining was detected in 27/52 (52%) of the tumors. MMP-9 immunoreactivity did not correlate with the main clinicopathological characteristics of the patients (localisation, T-stage, N-stage, histological grading), but correlated with worse survival of the patients. MMP-9 negative tumors showed a significant lower mean MVD per microscopic field than MMP-9 positive tumors (p<0. 001). There was a significant association of MMP-9 and VEGF expression (p<0.05). The presence of MMP-9 in HNSCC cancer and the positive correlation with MVD and VEGF expression supports the theory that MMP-9 functions as a regulator of tumor angiogenesis supporting endothelial cell invasion. MMP-9 and VEGF might act co-operatively in the process of neovascularization in human head and neck cancer.
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PMID:Expression of 92-kDa type IV collagenase correlates with angiogenic markers and poor survival in head and neck squamous cell carcinoma. 1107 94

There have been a number of reports suggesting inhibition of prostaglandin production may impact tumor-mediated wasting and levels of associated humoral factors such as hypercalcemia. These reductions were achieved using traditional nonsteroidal anti-inflammatory drugs (NSAIDs), which are often contraindicated in cancer patients. This is especially true during chemotherapeutic regimens due to concerns of bleeding from gastrointestinal and hematopoietic toxicities associated with inhibition of the housekeeping cyclooxygenase enzyme COX-1. Here, we report that celecoxib, one of the new class of selective COX-2 inhibitors, has the potential to reverse tumor-mediated wasting and associated humoral factors such as interleukin (IL)-6 and hypercalcemia in preclinical models of cachexia. Tumor bearing mice in late stage cachexia regained weight within days of the start of celecoxib treatment. Two models were tested. The first was the Colon 26 (Col26) syngeneic murine model that induces high levels of circulating IL-6 and hypercalcemia. The second was the human head and neck 1483 HNSCC xenograft model, which is less inflammatory and produces less prostaglandin than Col26. Despite the observation that no significant impact on tumor growth was observed between vehicle and celecoxib-treated animals over the course of the studies, celecoxib rapidly reversed weight loss in both cachectic models. With the added safety of celecoxib over traditional NSAIDs, these results suggest a possible therapeutic use for celecoxib for treating tumor-mediated wasting.
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PMID:Inhibition of cyclooxygenase-2 by celecoxib reverses tumor-induced wasting. 1471 36

The suppressors of cytokine signaling (SOCS) are inhibitors of cytokine signaling that function via the Janus kinase (JAK)/signal transducers and activators of transcription (STAT) pathway. Recently, methylation of SOCS-1 and SOCS-3 has been implicated in the tumorigenesis of liver and lung cancer. This study was performed to elucidate the role of SOCS-1 and SOCS-3 in squamous cell carcinoma of the head and neck (HNSCC) and its precursor lesions. HNSCC of 94 patients and corresponding normal mucosa, lymph node metastases as well as 16 high- and 21 low-grade squamous cell dysplasias were studied by using methylation-specific PCR (MSP) for the SOCS-1 and SOCS-3 promoter after microdissection. The presence of SOCS-3 mRNA transcripts was confirmed by semiquantitative real-time PCR, and the SOCS-3 protein was analysed immunohistochemically. SOCS-3 hypermethylation was found in 85/94 HNSCC (90%) and in 10/16 high-grade and 9/21 low-grade dysplasias (63 and 43%, respectively). SOCS-1 promoter hypermethylation was detected in 10/94 HNSCC samples (11%) and in 2/16 high-grade and 1/21 low-grade dysplasias (13 and 5%, respectively). Lymph node metastases exhibited an identical methylation status as the primary tumors. Methylation of the SOCS-3 promoter correlated with downregulation of SOCS-3 transcripts and protein expression in these tumors and various cell lines. In the cell lines tested, SOCS-3 and SOCS-1 transcripts increased upon treatment with the demethylation compound 5-aza-2-deoxycytidine (5-AZA-DC). Overexpression of wild-type SOCS-3 in carcinoma cells with methylated SOCS-3 resulted in the induction of apoptosis and growth suppression as well as downregulation of STAT3, bcl-2 as well as bcl-xL. Our data suggest that promoter methylation and subsequent transcript downregulation of SOCS-3 transcripts and, to a much lesser extent, SOCS-1 are involved in the multistep carcinogenesis of HNSCC. During its involvement in tumor growth, restoration of SOCS-3 may hold treatment potential for HNSCC.
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PMID:SOCS-3 is frequently methylated in head and neck squamous cell carcinoma and its precursor lesions and causes growth inhibition. 1600 69

Although head and neck cancer is a common malignancy, investigations have not yet improved the poor prognosis of patients. Therefore, it is important to find new cancer treatment modalities. Recent studies showed that cyclooxygenase, especially its isoform cyclooxygenase-2, is involved in tumorigenesis, tumor growth and metastasis. Inhibition of this enzyme by cyclooxygenase inhibitors has been shown to be antiproliferative in numerous cancer cell lines. The aim of this study was to investigate if the selective cyclooxygenase-2 inhibitor nimesulide could enhance cytotoxicity of the standard chemotherapeutic agent cisplatin. Head and neck squamous cell cancer cells were incubated with nimesulide and/or cisplatin, and counted after 24, 48 and 72 h treatment. Visualization of apoptotic cells was done by immunohistochemistry. We demonstrated that nimesulide inhibits the cytotoxic effect of cisplatin in HNSCC cells. Therefore, COX-2 inhibitor nimesulide may not be a good partner for cisplatin in combination therapy for cancer.
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PMID:Inhibition of cytotoxicity of cisplatin by cyclooxygenase-2 inhibitor nimesulide in head and neck cancer cell lines. 1627 49

LZAP has been reported to inhibit cellular proliferation and clonogenic growth. Here, we report that decreased LZAP expression promoted cellular transformation, xenograft tumor growth, and xenograft tumor vascularity. Loss of LZAP also increased cellular invasion, and MMP-9 expression dependent on NF-kappaB. LZAP directly bound to RelA, impaired serine 536 phosphorylation of RelA, increased HDAC association with RelA, inhibited basal and stimulated NF-kappaB transcriptional activity, and was found at the promoter of selective NF-kappaB-responsive genes. LZAP protein levels were markedly decreased in 32% of primary HNSCCs (n = 28) and decreased LZAP levels in primary HNSCC correlated with increased expression of the NF-kappaB-regulated genes IL-8 and IkappaBalpha. In aggregate, these data support a role of LZAP in NF-kappaB regulation and tumor suppression.
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PMID:LZAP, a putative tumor suppressor, selectively inhibits NF-kappaB. 1778 5

Squamous cell carcinoma of the head and neck (HNSCC) is the seventh most common cancer in the United States. Angiogenesis, the process by which new blood vessels are formed, is an essential element at the basis of both tumor growth and metastases. This review discusses pertinent aspects of the role of imaging modalities in assessing angiogenesis and anti-angiogenic therapy in advanced HNSCC.
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PMID:Non-invasive imaging of angiogenesis in head and neck squamous cell carcinoma. 2038 43

The epidermal growth factor receptor (EGFR) is a validated target in squamous cell carcinoma of the head and neck (HNSCC). However, despite high expression of EGFR in these cancers, EGFR inhibitor monotherapy has only had modest activity. Potential mechanisms of resistance to EGFR-targeted therapies involve EGFR and Ras mutations, epithelial-mesenchymal transition, and activation of alternative and downstream pathways. Strategies to optimize EGFR-targeted therapy in head and neck cancer involve not only the selection for patients most likely to benefit but also the use of combination therapies to target the network of pathways involved in tumor growth, invasion, angiogenesis, and metastasis.
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PMID:New strategies in head and neck cancer: understanding resistance to epidermal growth factor receptor inhibitors. 2040 34


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