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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cancer is a real challenge for modern medicine. Biologically, it is of a host origin and therefore its eradication appears not so easy as one could expect to do it. Cancer presents itself with many faces as if it would be Janus the deity. The basic knowledge on tumorigenesis at the level of evolutionary science is weak. Additionally, accumulating molecular data are still focused on experimental systems, but more important fact is to determine the molecular pathobiology that could have impact on improvement of control of malignant disease. Poland is among the countries with high cancer morbidity and mortality. Multidisciplinary approach to detect, control, and treat cancer diseases is the only way to get improved clinical results. Moreover, it is worth pointing out that individual considerations of every patient would offer clinical benefits. Biology of human tumors with the modem armament of molecular and chemical methods would be a help-hand to construct novel drugs. Making a list of crucial pathways worth blocking with their translation into clinical benefits appears to be a great step forward. Chemistry is a real partner to modem medicine due to a technical possibility to have impact on molecules (xenobiotics) that will finally become approved drugs. Combinatorial chemistry offers automated methods for pipeline organic synthesis a large number of chemicals that are further capable of undertaking investigation at a bed. Many chemicals have been used for more than ten years upon treating various cancer patients. New drugs have various origin , i.e., monoclonal antibodies (Herceptin, Erbitux, Avastin) or small molecules (Glivec, Tarceva, Sutent, Nexavar). We do hope that in the future many new drugs will be available for treatment of particular disease in relation to genetic characterization of individual patient's tumor. At the same time, we realize the great need for changes in the financial facets of modem individual treatment, and hoping not to hamper the development of new drugs due to the lack of financial solution how to make new and expensive drugs available to many patients.
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PMID:Molecular underpinnings of the targeted therapy for cancer. 1917 44

We report the detailed molecular study of angiogenesis-ralated genes and target therapy of the case of a male 46-year-old patient with extrarenal rhabdoid tumor of pelvic retroperitoneum. The patient was found to have a huge pelvic soft tissue sarcoma and underwent pelvic tumorectomy and appendectomy. The microscopically morphological features and molecular profile by immunohistochemical analysis supported the surgical histological diagnosis of extrarenal rhabdoid tumor. The tumor recurred two weeks after surgery and metastasized to the lung, left abdominal wall and mesenteric lymph nodes. Systemic chemotherapy including ifosfamide, liposomal doxorubicin, Taxol and cisplatin, concurrently with pelvic radiotherapy (58 Gy of total dose). However, the patient did not respond to the combination of chemotherapy and radiotherapy. Immunohistochemical staining and fluorescence in situ hybridization of tumor cells indicated negative expression of human epidermal growth factor receptor-2 (HER-2) and epidermal growth factor receptor (EGFR) and positive expression of vascular endothelial growth factor (VEGF) and vascular endothelial growth factor receptor (VEGFR). So anti-VEGF targeted therapy (Bevacizumab) was administered following the fourth course chemotherapy. However, the condition worsened after the administration of the second cycle of Bevacizumab. Multiple organ failure led to the death of the patient. The patient only survived five months and 20 days after the surgery of the primary tumor.
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PMID:Case report of extrarenal rhabdoid tumor of pelvic retroperitoneum molecular profile of angiogenesis and its implication in new treatment strategy. 1927 48

Breast cancer (BC) is the most common neoplasm in women in Western countries. Tumoral angiogenesis (TA) is essential for the growth and spread of BC cells. There are at least 6 different angiogenic growth factors associated with TA in BC. The major mediator of TA is vascular endothelial growth factor (VEGF), a homodimeric heparin-binding glycoprotein. VEGF signals through VEGF receptor-2 (VEGFR-2), the major VEGF signalling receptor that mediates sprouting angiogenesis. Recently, different antiangiogenic agents have shown efficacy in the treatment of advanced BC. Bevacizumab, a humanised monoclonal antibody against VEGF, in combination with taxanes improves progression-free survival and overall response rate in first-line therapy. Other new antiangiogenic agents, called multi-kinase inhibitors (sunitinib and pazopanib), are under investigation. Finally, a schedule of treatment called metronomic chemotherapy, with antiangiogenic activity, has also demonstrated efficacy in the treatment of advanced BC.
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PMID:Tumoral angiogenesis and breast cancer. 1929 50

Neoplastic angiogenesis is an essential process in the progressive growth of neoplasms and the production of metastasis. Angiogenesis consists of a series of linked and sequential steps that ultimately leads to the development of a neovascular blood supply to the tumor mass. VEGF has got an essential role in neoplastic angiogenesis, therefore it is an important target in the treatment of neoplasms. Bevacizumab, a humanized monoclonal antibody, inhibits VEGF, and may also improve the delivery of chemotherapy to the tumor mass. Multi-kinase ihibitors (sorafenib and sunitinib) are orally administered small-molecules, that inhibit different receptors (essentials in the neoplastic angiogenesis), such as the VEGFR or PDGFR. These agents are useful in the treatment of advanced renal-cell carcinoma, and are under investigation in several tumors.
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PMID:[Neoplastic angiogenesis]. 1929

Lung cancer is the leading cause of cancer-related mortality in the United States. Patients treated with adjuvant chemotherapy have a 5-year survival rate of 25% to 70% depending on stage, whereas those with advanced disease have a median survival of approximately 8 months when treated with standard platinum-based therapy. Improvements in our understanding of cancer biology have led to the development of novel agents that more precisely affect the target of interest, allowing for a more rational approach to clinical trial design. Angiogenesis, the growth of new vessels from preexisting vessels, is a fundamental step in tumor growth and progression. Inhibition of tumor-related angiogenesis has become an attractive target for anticancer therapy. Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), is the most studied antiangiogenic agent in patients with non-small-cell lung cancer (NSCLC). There was an improvement in overall survival when bevacizumab was combined with paclitaxel and carboplatin in patients with advanced NSCLC that was not seen when bevacizumab was combined with cisplatin and gemcitabine. Studies with bevacizumab in the adjuvant and advanced setting are ongoing in patients with NSCLC. Small-molecule inhibitors targeting the VEGF receptor and the tyrosine kinase receptor have also shown promise when combined with standard chemotherapy, but their role in the treatment of patients with NSCLC remains to be determined. This article reviews clinical trials that have incorporated antiangiogenic agents in the treatment of patients with NSCLC.
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PMID:Emerging data with antiangiogenic therapies in early and advanced non-small-cell lung cancer. 1936 48

In the past 10 years, tremendous headway has been made in the fight against colorectal cancer. Advances have included the approval of new cytotoxic agents (oxaliplatin, irinotecan, and capecitabine), as well as biologic agents (cetuximab, bevacizumab, and panitumumab). Studies of bevacizumab, an antibody that targets vascular endothelial growth factor, provided the first proof of principle that addition of antiangiogenic therapy to chemotherapy provided a survival benefit for patients with previously untreated metastatic colorectal cancer. Since then, data have shown that bevacizumab treatment provides this same benefit in the second-line setting. Bevacizumab also appears to be effective when added to various chemotherapy regimens. The mechanisms of action of bevacizumab appear to involve both decreasing the number of abnormal tumor blood vessels that feed the tumor and preventing the growth of future blood vessels; and normalizing the abnormal tumor blood vessels to allow for better delivery of chemotherapy. Future research directions in the setting of metastatic colorectal cancer include continued evaluation of bevacizumab combined with different chemotherapeutic regimens, use of bevacizumab as maintenance therapy, continuation of bevacizumab through multiple lines of treatment, and bevacizumab combined with other biologic agents, such as epidermal growth factor receptor inhibitors.
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PMID:Antiangiogenic agents in first-line and second-line therapy for advanced colorectal cancer. 1936 74

Interleukin-6 (IL6) and vascular endothelial growth factor (VEGFA) are abundantly produced by glioma cells and contribute to malignancy by promoting angiogenesis, cell proliferation and resistance to apoptosis. We compared the effect of inhibiting IL6 and VEGF on U87-derived experimental glioma grown on the chick chorio-allantoic membrane (CAM) or in the brain of xenografted mice. Tumor growth was monitored by biomicroscopy and immunohistology. In vitro, IL6 knockdown had no effect on proliferation but substantially enhanced invasion. In the CAM experimental glioma, IL6 or VEGF knockdown reduced growth and vascularization of the tumors with a comparable efficiency, but increased invasion of residual tumor cells. In contrast, combined IL6/VEGF knockdown not only showed enhanced reduction of tumor growth and angiogenesis but also significantly prevented invasion of residual tumor cells. In mice, combining IL6 knockdown and Avastin treatment completely abrogated tumor development and infiltration. Molecular response of tumor cells to single or combined treatment was studied by transcriptomic profiling. Many cell cycle promoting genes and chromatin components were silenced in the double knockdown. In addition, specific migratory signatures detected in tumors under single IL6 or VEGF knockdown were partially erased in combined IL6/VEGF knockdown tumors. Our results show that treatment with a combination of IL6 and VEGF inhibitors brings synergistic antitumoral benefit and reduces global activity of major pathways of cell survival, proliferation and invasiveness in remaining tumor cells that may be induced by using VEGF or IL6 inhibitors alone.
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PMID:Combined targeting of interleukin-6 and vascular endothelial growth factor potently inhibits glioma growth and invasiveness. 1943 Nov 43

Human lung cancer is the leading cause of cancer death worldwide. Bevacizumab, a monoclonal antibody against vascular endothelial growth factor (VEGF), in combination with chemotherapy showed significant therapeutic efficacy in human lung cancer patients. However, increased adverse effects limit its clinical utilization. Previous studies demonstrated that polysaccharide beta-glucan significantly augments antitumor monoclonal antibody-mediated efficacy via stimulation of the innate effector neutrophil complement receptor 3. Here, we explored combined beta-glucan with bevacizumab therapy for human lung cancer using murine xenograft models. To that end, human lung adenocarcinomas were screened for membrane-bound VEGF expression. Both subcutaneous and orthotopic lung cancer xenograft models were used to evaluate the combination therapy. We found that PC14PE6 adenocarcinoma cells express membrane-bound VEGF both in vitro and in vivo. Bevacizumab bound to surface VEGF on PC14PE6 cells and activated complement. In the subcutaneous PC14PE6 tumor model, beta-glucan plus bevacizumab showed augmented efficacy in terms of tumor progression and long-term survival compared with bevacizumab-treated alone. These effects were accompanied with massive complement deposition and neutrophil infiltration within tumors. However, this effect was not observed in surface-bound VEGF-negative human lung tumors. Therapeutic efficacy of beta-glucan with bevacizumab was further demonstrated in an orthotopic lung cancer model. Thus, our data suggest that beta-glucan enhances bevacizumab-mediated efficacy and may provide therapeutic benefits for lung cancers with membrane-bound VEGF expression.
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PMID:Effect of yeast-derived beta-glucan in conjunction with bevacizumab for the treatment of human lung adenocarcinoma in subcutaneous and orthotopic xenograft models. 1956 38

Renal cell carcinoma (RCC) is very resistant to both chemotherapy and radiotherapy. Localized disease can be cured by surgery but most patients are diagnosed when distant metastases are already present and about 30% of patients relapse after nephrectomy. Until 2 years ago, cytokine-based immunotherapy (interleukin-2 and interferon-alpha) was the only therapeutic option for advanced RCC patients. Fewer than 20% of patients benefit from this treatment, but some of these may experience very prolonged complete responses and progression-free intervals, suggesting a possibility of cure in a very few cases. Thanks to our expanding knowledge of the biology and pathogenesis of RCC, the treatment of this disease has recently undergone a major advance, through the development of potent angiogenesis inhibitors and targeted agents. Bevacizumab, an antibody directed against vascular endothelial growth factor (VEGF), has shown significant activity in combination with interferon-alpha (IFN-alpha). Sunitinib and sorafenib, multikinase inhibitors with proven antiangiogenic activity, have also been approved for the treatment of this tumor. Finally, temsirolimus and everolimus, which belong to the family of mammalian target of rapamycin (mTOR), have shown some activity in selected patients. The aim of this paper is to review clinical trials with these new agents, describing their activity and profiles of toxicity, and to evaluate potential future developmental strategies.
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PMID:A survey of therapy for advanced renal cell carcinoma. 1957

To understand the mechanisms of the effects of combination treatments, we established animal models showing antitumor activity of bevacizumab as a monotherapy and in combination with capecitabine or capecitabine and oxaliplatin and measured thymidine phosphorylase (TP) and vascular endothelial growth factor (VEGF) levels. Tumor-inoculated nude mice were treated with bevacizumab, capecitabine, and oxaliplatin, alone or in combination, after tumor growth was confirmed and volume and microvessel density (MVD) in tumors were evaluated. Levels of TP and VEGF in the tumor were examined by ELISA. Bevacizumab showed significant antitumor activity as a monotherapy in three xenograft models (COL-16-JCK, COLO 205 and CXF280). The MVD in tumor tissues treated with bevacizumab was lower than that of the control. Antitumor activity of bevacizumab in combination with capecitabine was significantly higher than that of each agent alone (COL-16-JCK, COLO 205). Furthermore, the antitumor activity of bevacizumab in combination with capecitabine + oxaliplatin was significantly superior to that of capecitabine + oxaliplatin (COL-16-JCK). TP and VEGF levels were not increased by bevacizumab or capecitabine, respectively, suggesting there are other potentially efficacious mechanisms involved. In the present study we established human colorectal cancer xenograft models which reflect the efficacy of clinical combination therapies, capecitabine + bevacizumab and capecitabine + oxaliplatin + bevacizumab. We will further investigate the mechanisms of the combination therapies using these models.
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PMID:Antitumor activity of bevacizumab in combination with capecitabine and oxaliplatin in human colorectal cancer xenograft models. 1957 62


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