Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

DCs are the most potent antigen-presenting cells that play a major role in initiating the antitumor immune response. Although the clinical significance of TIDCs has been investigated in a variety of human cancers, few studies have focused on the in situ maturation status of DCs. We have analyzed the maturation-specific significance of TIDCs in the prognosis of patients with breast carcinoma. We evaluated 130 breast carcinomas for the presence of TIDCs using immunohistochemistry with an anti-CD1a antibody for immature DCs and an anti-CD83 antibody for mature DCs. Intratumoral expression of immunosuppressive cytokines was also examined. All samples contained CD1a(+) TIDCs, and 82 (63.1%) samples contained CD83(+) TIDCs. The number of CD83(+) TIDCs was inversely correlated with lymph node metastasis and with tissue expression of VEGF and TGF-beta, whereas the number of CD1a(+) TIDCs was not. Kaplan-Meier analysis (log rank statistics) revealed a significant association of increasing number of CD83(+) TIDCs with longer relapse-free (p = 0.002) and overall (p < 0.001) survival. Furthermore, among patients with lymph node metastasis, the survival rate of those with larger numbers of CD83(+) TIDCs was significantly better than that of patients with fewer CD83(+) TIDCs. Multivariate analysis revealed that CD83(+) TIDCs had independent prognostic relevance in breast carcinomas. The infiltration of tumors by mature DCs expressing CD83 may be of great importance in initiating the primary antitumor immune response and is confirmed as an independent, immunologic prognostic parameter for survival in patients with breast cancer.
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PMID:Prognostic value of tumor-infiltrating dendritic cells expressing CD83 in human breast carcinomas. 1253 24

Angiogenic cytokines in the plasma and serum of cancer patients may serve as 'surrogate' markers of tumour neoangiogenesis. Serum VEGF correlates with disease stage in colorectal cancer (CRC), but the role of bFGF in CRC is uncertain. This study aimed to assess plasma bFGF levels in CRC patients before treatment, during chemoradiotherapy and at one-year follow-up. Plasma samples were taken from 124 CRC patients, 26 polyp patients and 55 controls, and bFGF levels were measured by ELISA. 19 patients underwent pre-operative chemoradiotherapy. One-year follow-up samples were available from 48 disease-free patients and 18 patients with progressive disease. There were no detectable differences between plasma bFGF levels in polyp, Dukes' A or B patients (4.55, 5.77, 4.25 pg/ml, respectively), but there was a significant increase in metastatic CRC patients [Dukes' C and D (7.42 and 6.6 pg/ml; P = 0.004 and 0.048, respectively)], relative to median control levels of 4.14 pg/ml. At follow-up, there was a significant fall in plasma bFGF levels in disease-free patients (pre-op 6.09 and follow-up 3.45 pg/ml, P = 0.0004), but a non-significant rise in 18 patients with progressive disease (pre-treatment 5.90 and follow-up 9.99 pg/ml, P = 0.33). Pre-treatment plasma bFGF in patients receiving chemo-radiotherapy was similar in those with responsive and non-responsive tumours. There were no detectable changes in plasma bFGF through the adenoma-carcinoma sequence or patient groups with non-metastatic cancers. Elevated plasma bFGF was, however, associated with metastatic spread. The significant fall in bFGF in disease-free patients following therapy suggests that bFGF may be useful in clinical practice.
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PMID:Plasma basic fibroblast growth factor levels in colorectal cancer: a clinically useful assay? 1255 80

In the past few years, new agents based on monoclonal antibodies have been developed in Oncology. Indeed in some case tumor cells express antigenic targets at higher levels than normal cells. There are 2 main types of monoclonal antibodies that can be either conjugated to cytotoxic drugs or radio-active compounds or be non-conjugated. Among the last category, some are currently used in the treatment of patients, including 2 monoclonal antibodies targeting receptors with tyrosine kinase activity (HER2: Herceptin (DCI: trastuzumab), EGFr: Erbitux (DCI: cetuximab). A third monoclonal antibody is commonly used in cancer treatment, which targets CD20, a transmembrane marker of B lymphoma (MabThera (DCI: rituximab). Both Herceptin and MabThera have been associated with improved survival in patients with breast carcinoma and lymphoma, respectively. New promising agents are under investigation such anti EGFr in colon and head and neck carcinoma or new compounds such as anti-VEGF. These examples outline the importance of the recent progress in selectively targeting tumor antigen and the potential impact of these approaches in Oncology.
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PMID:[Principal therapeutic uses of monoclonal antibodies in oncology]. 1258 79

Hybridization with cDNA arrays was used to obtain expression profiles of 263 protein-tyrosine kinase (PTK), protein-tyrosine phosphatase (PTP), dual-specific phosphatase (DuSP), and other genes for the normal prostate tissue, primary prostate carcinomas (PC) of 84 patients, 7 xenografts, and 5 carcinoma cell lines. Analysis of 96 profiles revealed eight clusters of genes coexpressed in PC (coefficient of correlation r > 0.7). According to the known functions of their genes, the clusters were designated as proliferating-cell (CDC42, TOP2A, FGFR3, MYC, etc.), neoangiogenesis and blood-cell (LCK, VAV1, KDR, VEGF, MMP9, SYK, PTPRS, and FLT4), invasion-1 and invasion-2 (ADAM17, TRPM2, DUSP6, VIM, CAV1, CAV2, JAK1, PTPNS1, FYN, and PDGFB), HER2, and PSA/PSM/HER3. Basing on expression profiles of 66 genes, a molecular classification of PC was constructed and allowed discrimination between PC and cell lines or xenografts at 98.9% probability. The results suggested that, along with PSA, PSM (FOLH1), kallikrein-2, and a-2-macroglobulin, cell signaling genes EGFR, HER2, HER3, TOP2, KRT8, KRT18, VEGF, CD44, VIM, CAV1, and CAV2 may serve as diagnostic and prognostic markers in PC. The HER2, VEGF, and CD44 genes and the MMP and ADAM families were assumed to be promising targets for inhibitors of PC cell proliferation and metastasis.
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PMID:[Gene expression profiles of protein kinases and phosphatases obtained by hybridization with cDNA arrays: molecular portrait of human prostate carcinoma]. 1262 52

We describe the third case world-wide of a chorangiocarcinoma, a tumour with an abnormal trophoblast proliferation in combination with a hypervascular chorangiosis of the villous stroma. The lesion was an incidential finding by a healthy 31-year-old woman, gravida 1, para 1 when the pregnancy was terminated at 34 weeks gestation because of fetal distress and intrauterine growth restriction. Hormonal levels were within the normal range. Mother and infant had an uneventful postpartum course. Immunohistochemical studies of the abnormal trophoblasts demonstrated strong immunoreactivity for HCG and in 80% for Ki 67. The semiquantitative expression of angiogenic growth factors (VEGF, bFGF, Ang-1 und Ang-2, PDGF) in the tumour trophoblasts was similar to that seen in the normal villi. The pathogenesis of this tumour with a villous vascular response is curious and unclear. Possibilities include the occurrence of a variant of a chorion carcinoma, the occurrence of a new tumour entity or of two separate lesions, a chorangioma and incidential chorion carcinoma, present together as a "collision" tumour. Another possibility is a composition tumour or a reactive lesion of trophoblasts and the villous vascular tree.
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PMID:[Incidental chorangiocarcinoma. Case report, immunohistochemistry and theories of possible histogenesis]. 1267 2

HIF-1 is reported to transactivate expression of VEGF, which is an important angiogenic factor. To determine whether HIF-1alpha plays a role in angiogenesis through its regulation of VEGF, we examined expression of HIF-1alpha and its relation to clinicopathologic features, VEGF expression and prognosis of patients with colorectal carcinoma. Expression of HIF-1alpha and VEGF was examined in 4 colorectal carcinoma cell lines (COLO320DM, COLO201, DLD-1, WiDr) and 149 colorectal carcinoma tissues (10 fresh specimens, 139 archival, paraffin-embedded specimens). HIF-1alpha protein levels were increased by hypoxia in 3 of 4 colorectal carcinoma cell lines (COLO201, DLD-1, WiDr), and VEGF mRNA levels were also increased by hypoxia in the same cell lines. In 8 of 10 patients with colorectal cancer, expression of HIF-1alpha and VEGF was increased in tumor tissues compared to corresponding normal mucosa. Of 139 archival specimens of colorectal carcinoma, 81 (58.3%) expressed HIF-1alpha protein at a high level. HIF-1alpha expression was correlated with tumor invasion, tumor stage, lymphatic invasion, venous invasion and liver metastasis. Moreover, HIF-1alpha expression was correlated significantly with VEGF expression and microvessel density. Although there was a tendency for poorer prognosis in patients with high HIF-1alpha-expressing tumors, this correlation was not statistically significant. These findings suggest that HIF-1alpha may play a role in angiogenesis and tumor progression via regulation of VEGF in human colorectal carcinoma.
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PMID:Expression of hypoxia-inducible factor-1alpha is associated with tumor vascularization in human colorectal carcinoma. 1267 75

Undifferentiated nasopharyngeal carcinoma (NPC) is closely associated with EBV infection, and the EBV-encoded latent membrane protein 1 (LMP1) is frequently detected in NPC. However, little is known about the pathologic roles of LMP1 in this disease. Recently, we reported the morphologic transformation and increased expression of the LAMC2 and ITGalpha6 genes in LMP1-expressing NPC cell lines. In this study, we further examine the effects of LMP1 in an immortalized nasopharyngeal epithelial cell line called NP69. This cell line was established from primary nonmalignant nasopharyngeal epithelial cells and may represent a model of premalignant nasopharyngeal epithelial cells. LMP1 induced many phenotypic changes in NP69 cells. These include morphologic transformation, increased cell proliferation, anchorage-independent growth, resistance to serum free-induced cell death, and enhanced cell migration and invasion. In addition, expression array analysis identified 28 genes that demonstrated a more than 2-fold difference in expression of NP69 cells expressing LMP1 when compared with a vector control. Two of the up-regulated genes (VEGF and vimentin) identified have been previously reported as LMP1 targets. The majority of the identified genes are associated with cell growth, differentiation, cell shape, and invasion. The present findings support the proposed roles of LMP1 in promoting cell transformation, migration, and invasion in premalignant nasopharyngeal epithelial cells. The present study also indicates the activation of the Ras/MAPK pathway in LMP1-expressing cells, which may be involved in mediating some of the transforming effects of LMP1 observed in nasopharyngeal epithelial cells.
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PMID:Alterations of biologic properties and gene expression in nasopharyngeal epithelial cells by the Epstein-Barr virus-encoded latent membrane protein 1. 1274 79

In this study we describe and discuss the dichotomous effects of docetaxel trastuzumab (Herceptin)/docetaxel therapy on the angiogenic molecular profile in two patients with her-2 + chemo-resistant recurrent breast carcinoma. In the first case, an intensification of angiogenesis occurred following therapy, accompanied by an impressive increase of the cancer cell proliferation index. This tumor did not express HIF1 alpha and shared a HIF-independent VEGF overexpression, which remained unaffected by therapy. An intensified formation of thymidine phosphorylase (TP)-rich stroma, presumably a response to docetaxel, shows a TP-dependent angiogenic response. In the second patient, VEGF and HIF1 alpha were down-regulated in post-treatment biopsies and this was accompanied by a sharp reduction of the vascular density and of the cancer cell proliferation rate. In both cases, c-erbB-2 expression was abrogated by Herceptin. Taking into account that Herceptin down-regulates VEGF through reduction of HIF1 alpha synthesis, this clinical study provides evidence that an anti-angiogenic effect from Herceptin/Docetaxel therapy is expected only in tumors with HIF1 alpha-dependent VEGF overexpression. In contrast, HIF1 alpha-independent VEGF angiogenic activity cannot be abrogated by Herceptin. Docetaxel mediated up-regulation of TP in the tumoral stroma may, on the contrary, result in angiogenesis intersification and rapid tumor relapse. Such an effect should be of clinical importance since Herceptin/Docetaxel-based regimens are currently evaluated for the adjuvant therapy of her-2 + breast cancer patients. Studying the Herceptin-induced phenotypic changes of tumors could lead to the identification of specific molecular profiles that bring about diverging angiogenic responses. Adjustment of the chemotherapy regimen accordingly would prove of clinical importance.
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PMID:The effect of trastuzumab/docatexel combination on breast cancer angiogenesis: dichotomus effect predictable by the HIFI alpha/VEGF pre-treatment status? 1282 Apr 39

Two receptors, neuropilin 1 (NP1) and neuropilin 2 (NP2), bind class 3 semaphorins, axon guidance molecules including SEMA3F, the gene for which was isolated from a 3p21.3 deletion in lung cancer. In addition, they bind VEGF (vascular endothelial growth factor), enhancing the effects of VEGF binding to KDR/Flk-1. Elevated VEGF levels are associated with the loss and cytoplasmic delocalization of SEMA3F in lung cancer, suggesting competition for their NP1 and NP2 receptors. To determine the timing of these events, we compared by immunohistochemistry VEGF, SEMA3F, NP1 and NP2 expression in 50 preneoplastic lesions and 112 lung tumours. In preneoplastic lesions, VEGF increased from low-grade to high-grade dysplasia (p=0.001) whereas SEMA3F levels remained low. NP1 and NP2 levels increased from dysplasia to microinvasive carcinoma (p=0.0001) and correlated with VEGF expression (p=0.04 and 0.0002, respectively). Non-small cell lung carcinoma overexpressed VEGF and NP1 and NP2 significantly more often than neuroendocrine tumours including small cell lung carcinoma. SEMA3F loss or delocalization correlated with advanced tumour stage. Migrating cells overexpressed VEGF, SEMA3F, NP1 and NP2 with cytoplasmic delocalization of NP1 as demonstrated in an in vitro wound assay. These results demonstrate early alteration of the VEGF/SEMA3F/NP pathway in lung cancer progression.
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PMID:Expression of VEGF, semaphorin SEMA3F, and their common receptors neuropilins NP1 and NP2 in preinvasive bronchial lesions, lung tumours, and cell lines. 1284 30

Various angiogenic and angiostatic factors regulate angiogenesis. Tumor angiogenesis is a complicated process for which the detailed mechanisms remain unclear. The aim of this study was to elucidate the clinical significance of TSP-1 expression in relation to expression of VEGF and IL-10 and angiogenesis at the deepest invasive tumor site as a predictor of invasive/metastatic potential and prognosis of advanced colorectal carcinoma (CRC). Patients (n=152) who had undergone surgical resection for advanced CRC were entered in this study. Expression of TSP-1, VEGF, and IL-10 was examined immunohistochemically with specific antibodies. Tumor microvessel density (MVD) was also determined immunohistochemically with anti-CD34 antibody (NU-4A1). Expression of TSP-1, VEGF, and IL-10 at the deepest invasive tumor site was detected in 46 (30.3%), 62 (40.8%), and 39 (25.7%) of 152 lesions, respectively. TSP-1, VEGF, and IL-10 expression at the superficial part was detected in 60 (39.5%), 35 (23.0%), and 46 (30.3%) of 152 lesions, respectively. Although there was no significant difference between the incidence of TSP-1 and IL-10 expression at the deepest invasive site or at the superficial part, there was a significant difference between the incidence of VEGF expression at the deepest invasive site and that at the superficial part. Expression of TSP-1 and IL-10 at the deepest invasive tumor site was inversely correlated with metastatic potential and prognosis in relation to MVD. Furthermore, lesions that were TSP-1-negative and VEGF-positive at the deepest invasive tumor site showed the strongest association with MVD. The 5-year survival rate for patients with TSP-1-negative or IL-10 negative lesions at the deepest invasive tumor site was significantly poorer than that for patients with TSP-1-positive or IL-10-positive lesions, respectively. The 5-year survival rate for patients with VEGF expression at the deepest invasive tumor site was significantly poorer than that for patients without VEGF expression. The 5-year survival rate for patients with TSP-1-negative, VEGF-positive lesions at the deepest invasive site were significantly poorer than that for patients with lesions without these characteristics. Multivariate analysis with logistic regression for 5-year survival in patients with curative surgery showed that lymph node metastasis and VEGF expression were significant prognostic factors. Although lack of TSP-1 or IL-10 expression was associated significantly with poorer prognosis, this may be less important in poorer prognosis than the presence of VEGF expression.
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PMID:Clinical significance of thrombospondin-1 expression in relation to vascular endothelial growth factor and interleukin-10 expression at the deepest invasive tumor site of advanced colorectal carcinoma. 1296 68


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