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

We examined plasma levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 54 patients with gastric carcinoma. Postoperative survival was significantly poorer in patients with plasma VEGF levels more than 10.0 pg/ml at the time of surgery. By an univariate analysis of the factors affecting survival, serosal invasion, lymph node metastasis, peritoneal dissemination, lymphatic vessel invasion, curability, and VEGF proteins were significant. By a multivariate analysis only VEGF levels and curability remained significant. Patients with recurrent disease, including liver metastasis, had significantly higher plasma VEGF concentrations than those with resectable primary tumors. VEGF, not bFGF, may serve as an independent prognosticator and a sensitive indicator for liver recurrence in patients with gastric carcinoma.
 ...
PMID:Plasma concentrations of VEGF and bFGF in patients with gastric carcinoma. 1077 24

We investigated the expression of vascular endothelial growth factor (VEGF) and microvascular density in 54 cases of invasive laryngeal squamous cell carcinoma (SCC) and in ten samples of normal laryngeal tissue using immunohistochemistry methods. The study also focused on the distribution of mast cells in and around the SCCs. The microvascular density in laryngeal carcinoma tissue was higher than that in normal tissue (P = 0.02). VEGF was localized in SCCs, stromal cells, endothelial cells, minor salivary glands, and non-cancer epithelium adjacent to the tumor. VEGF expression in the tumor cells was found in 13 of 54 cases (24.1%), whereas mast cells around the carcinomas were VEGF positive in all 54 cases. Staining of VEGF in SCCs was strong in the area of high microvascular density (P = 0.0002). Using a multi-labeling subtraction immunostaining method, VEGF-positive stromal cells were classified mostly as mast cells and, in a few instances, as macrophages. VEGF staining in SCCs was associated with the mast cell count (P = 0.0001). There was no distinct correlation between VEGF expression and pTNM stage of an SCC. In conclusion, the results suggest that VEGF might be an important angiogenic factor in cancer invasion. Laryngeal cancer cells and mast cells may control the angiogenic response by releasing VEGF.
 ...
PMID:Association of vascular endothelial growth factor and mast cells with angiogenesis in laryngeal squamous cell carcinoma. 1078 83

Angiogenesis, the process leading to the formation of new blood vessels from a preexisting vascular network, is necessary for tumor growth, invasion, and metastasis. Data from experimental and clinical studies indicate that breast carcinoma is an angiogenesis-dependent tumor. Most retrospective studies evaluating the prognostic value of determination of intratumoral microvessel density (IMD) at the vascular "hot spot" (a surrogate marker of angiogenesis) found that IMD is a significant and independent prognostic indicator in patients with both node-negative and node-positive breast cancers. More recently, the expression of certain endothelial growth factors has been tested. Among these, vascular endothelial growth factor (VEGF), the most potent endothelial cell mitogen and also a regulator of vascular permeability, is emerging as a powerful new prognostic tool. Eight of the nine published retrospective studies reported that VEGF is significantly associated with relapse-free survival, overall survival, or both. Patients with early stage breast cancer who have tumors with elevated levels of VEGF have a higher likelihood of recurrence or death than patients with low-angiogenic tumors, even if treated with conventional adjuvant therapy. High levels of VEGF can differentiate the subgroups of patients with breast cancer with poor prognosis who benefit minimally from conventional adjuvant therapy but who may benefit from validated anti-VEGF treatments.
 ...
PMID:Prognostic value of vascular endothelial growth factor in breast cancer. 1080 90

To understand the relationship between the expression of vascular endothelial growth factor (VEGF) and the growth, metastasis of hepatocellular carcinoma (HCC), immunohistochemistry and Northern blot were used to investigate VEGF protein and mRNA in 21 cases of HCC with and without metastasis. VEGF protein was found in 8 of 9 cases with metastasis, whereas only in 4 of 12 cases without metastasis. The positive rate of the former was significantly higher than that in the latter. VEGF mRNA was detectable in both carcinoma and its surrounding liver tissues, but its level in the former was 2-3 times higher than that in the latter. In carcinoma with metastasis, the mRNA level was 5-6 times higher than that without metastasis. It is concluded that VEGF is closely related to the growth of HCC as well as its metastasis and it might be a useful indicator for the metastatic potential of HCC.
 ...
PMID:Expression of vascular endothelial growth factor in hepatocellular carcinoma and its relationship to tumor growth and metastasis. 1080 93

Both epidermal growth factor receptor (EGF-R) signaling mechanisms and angiogenesis have been evaluated as independent targets for therapy of human pancreatic carcinoma, but a link between the two processes has been identified only recently. This study evaluated whether EGF-R blockade therapy with anti-EGF-R antibody C225 inhibits pancreatic carcinoma growth and metastasis in an orthotopic nude mouse model via tumor-mediated angiogenesis and whether gemcitabine potentiates this effect. In vitro treatment of human pancreatic carcinoma L3.6pl cells with C225 inhibited EGF-R autophosphorylation, producing a maximum of 20% cytostasis. Treatment with C225 plus gemcitabine resulted in additive cytotoxic effects that increased with increasing gemcitabine concentrations. Dose-dependent decreases in expression of the angiogenic factors vascular endothelial growth factor and interleukin 8 (but not basic fibroblast growth factor) were observed in the C225-treated cells (mRNA and protein levels). In L3.6pl tumors established in the pancreas of nude mice, systemic therapy with C225 alone and C225 in combination with gemcitabine resulted in growth inhibition, tumor regression, and abrogation of metastasis; median tumor volume was reduced from 538 to 0.3 and to 0 mm3, respectively. Gemcitabine treatment alone reduced median tumor volume from 538 to 152 mm3. Liver metastases were present in 50% of the controls, 30% of the gemcitabine-treated animals, and 20% of C225-treated animals. No macroscopically visible liver metastases were observed in the combination treatment group. As early as 11 days after C225 treatment, the median percentage of proliferating cell nuclear antigen-positive cells was substantially reduced compared with gemcitabine treatment alone (26% versus 73%, respectively) versus controls (92%), correlating with in vivo blockade of EGF-R activation. Similarly after 11 days treatment, production of vascular endothelial growth factor and interleukin 8 was significantly lower in C225 and C225 plus gemcitabine-treated tumors versus gemcitabine-treated and control tumors. Significant differences in microvessel density were observed 18 days after C225 or combination treatments (but not gemcitabine alone) in direct correlation with the difference in percentage of apoptotic endothelial cells, as visualized by double immunofluorescence microscopy. These experiments indicate that therapeutic strategies targeting EGF-R have a significant antitumor effect on human L3.6pl pancreatic carcinoma growing in nude mice which is mediated in part by inhibition of tumor-induced angiogenesis, leading to tumor cell apoptosis and regression. Furthermore, this effect is potentiated in combination with gemcitabine.
 ...
PMID:Epidermal growth factor receptor blockade with C225 plus gemcitabine results in regression of human pancreatic carcinoma growing orthotopically in nude mice by antiangiogenic mechanisms. 1081 19

The combination of 5-fluorouracil (5-FU) and cisplatin is used most commonly for gastric carcinoma. Recent studies have indicated that vascular endothelial growth factor (VEGF) is related to drug delivery through angiogenesis and vascular permeability. In this study, we evaluated the efficacy and toxicity of continuous infusion of 5-FU and low dose cisplatin infusion as first-line treatment in patients with unresectable gastric adenocarcinoma. We also examined the relationship between chemotherapy response and immunohistochemical expression of VEGF in the biopsy samples of gastric primary. All 30 patients enrolled in this study were assessable for response, adverse reactions, and VEGF expression. The regimen consisted of 5-FU (350 mg/m2/day every day by continuous venous infusion) and low dose cisplatin (7 mg/m2/day by drip infusion over 1 h on days 1-5 every week). This treatment was repeated weekly for 3 consecutive weeks. Four weeks after the second cycle, mesurable lesions were estimated for response. An overall response rate was 46.7% (14/30). Patients with intestinal histologic type (10/12) and good performance status ([PS], 13/18) showed good response rate (83.3%, and 72.2%, respectively) compared to patients with diffuse histologic type (4/18) and poor PS [(1/12) 22.2%, and 8. 3%, respectively]. The response rate of VEGF-positive cases and VEGF-negative cases was 75% (12/16), and 16.7% (2/14), respectively. Multivarite analysis revealed that VEGF-positive and good PS had a significant impact on chemotherapy response in this treatment. The most common garde 3 or higher toxicities were myelosuppression (30%) and diarrhea (13.3%). Continuous infusion of 5-FU and low dose cisplatin infusion is an effective treatment for patients with unresectable gastric carcinoma, and VEGF expression may be a useful predictor of chemotherapy response in this regimen.
 ...
PMID:Immunohistochemical expression of vascular endothelial growth factor can predict response to 5-fluorouracil and cisplatin in patients with gastric adenocarcinoma. 1085 55

Epithelial-stromal interactions are important not only in growth, development, and functional cytodifferentiation of the prostate but also in derangements of prostate gland such as BPH and prostate carcinoma. This chapter explores the roles of epithelium and stroma during this delicate process and highlights the role and mutual influence of each on the other. It also examines the importance of ECM in mediating the effects of androgens and drawn attention to estrogen and genetic factors in the process. During this process of epithelial-stromal interaction, growth factors play a central role in mediating the interactions. This chapter focuses on the role of several growth factors including epidermal growth factor, fibroblast growth factor, transforming growth factor alpha, transforming growth factor beta, insulin-like growth factor-1, vascular endothelial growth factor, nerve growth factor, platelet-derived growth factor, and hepatocyte growth factor. This chapter emphasizes the importance of epithelial-stromal interactions in tumorigenesis and highlights the switch of paracrine to autocrine mode during the process of carcinogenesis.
 ...
PMID:Growth factors and epithelial-stromal interactions in prostate cancer development. 1087 77

The expression of interleukin 8 (IL-8) by human gastric carcinomas directly correlates with tumor vascularity and disease progression. To determine whether IL-8 can act in an autocrine manner to regulate the expression of other disease-progression genes, we examined the expression of IL-8 receptors IL-8RA (CXCR1) and IL-8RB (CXCR2) in six different human gastric carcinoma cell lines and 38 surgical specimens of human gastric carcinomas. All of the gastric carcinoma cell lines expressed mRNA and protein for IL-8RA and IL-8RB protein. In all surgical specimens, the majority of the tumor cells and small vessel endothelial cells stained positive for IL-8RA and IL-8RB protein. In vitro treatment of human gastric cancer MKN-1 cells with exogenous IL-8 enhanced the expression of epidermal growth factor receptor, type IV collagenase (metalloproteinase-9), vascular endothelial growth factor, and IL-8 mRNA. In contrast, treatment with exogenous IL-8 decreased expression of E-cadherin mRNA. IL-8 treatment increased invasive capacity of MKN-1 cells, which was associated with activity of metalloproteinase-9. Collectively, these results demonstrate that human gastric carcinoma cells express receptors for IL-8 and that IL-8 may play a role in the progressive growth of human gastric carcinoma by autocrine/paracrine mechanisms.
 ...
PMID:Regulation of disease-progression genes in human gastric carcinoma cells by interleukin 8. 1091 18

The poly(L-glutamic acid)-paclitaxel (PG-TXL) conjugate has been shown to exhibit significantly greater antitumor activity than conventionally formulated paclitaxel (TXL) against solid tumors (Li et al., Cancer Res., 58: 2404-2409, 1998). Here we report that local tumor irradiation enhanced the distribution of PG-TXL given 24 h later to ovarian OCa-1 carcinoma implanted i.m. in C3Hf/Kam mice. Radiation significantly increased tumor uptake of PG-TXL and tumor vascular permeability, caused elevation of the serum concentration of vascular endothelial growth factor, and arrested OCa-1 cells in the G1 phase of cell cycle. The enhancement factors, as measured by incremental tumor growth delay compared with PG-TXL alone, ranged from 1.36-4.44. Complete tumor regression was also observed at a higher radiation dose (>10 Gy) and a higher PG-TXL dose (>80 mg equivalentTXL/kg). Furthermore, combined radiation and PG-TXL produced a significantly greater tumor growth delay than treatment with radiation and TXL when both drugs were given at the same equivalent TXL dose of 60 mg/kg 24 h after tumor irradiation (enhancement factors, 4.44 versus 1.50). These data suggest that conjugation of TXL to poly(L-glutamic acid) is necessary for improved response and that the supra-additive effect of combined radiation and PG-TXL therapy is due in part to modulation of the enhanced permeability and retention effect of macromolecules by radiation. We propose a treatment strategy combining radiation and macromolecular chemotherapy that may have important clinical implications in terms of scheduling and optimization of the therapeutic ratio.
 ...
PMID:Tumor irradiation enhances the tumor-specific distribution of poly(L-glutamic acid)-conjugated paclitaxel and its antitumor efficacy. 1091 31

We established a new cell line, AZ-P7a, with high peritoneal-metastatic potential in nude mice. AZ-P7a cells were derived from the human gastric carcinoma line AZ-521, which has low capacity for peritoneal dissemination. AZ-P7a cells developed peritoneal metastasis in 11 / 14 (78.6%) mice, whereas the parental AZ-521 cells developed metastasis in 2 / 6 (33.3%) mice. The metastatic foci in the peritoneum showed essentially the same histological appearance as those induced by parental cells. The tumorigenicity and the motile activity of AZ-P7a cells were stronger than those of the parental AZ-521 cells; in contrast, adhesion to the extracellular matrix and the production of vascular endothelial growth factor by AZ-P7a cells were decreased. In fluorescence-activated cell sorter (FACS) analysis, AZ-P7a cells expressed significantly greater levels of integrins alpha2, alpha3, alpha5, alpha6 and alphavbeta5, as compared with AZ-521 cells. However, alpha1, alpha4, alphavbeta3, hCD44H, hCD44v3, hCD44v6 and hCD44v10 were not expressed in either cell line. AZ-P7a cells developed no liver metastasis when administered by the intrasplenic injection method, though the highly liver metastatic cell line AZ-H5c showed the same rate of peritoneal dissemination as that exhibited by AZ-P7a cells after intraabdominal injection. These findings suggested that the mechanism of peritoneal dissemination differed from that of hematogenous metastasis. Moreover, the latter appears to be controlled by more complex mechanisms than the former. Thus, this cell line might be useful for investigating the mechanism of peritoneal dissemination of human gastric cancer.
 ...
PMID:A novel experimental mouse model of peritoneal dissemination of human gastric cancer cells: different mechanisms in peritoneal dissemination and hematogenous metastasis. 1092 Feb 79


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>