Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P10415 (Bcl-2)
 33,771 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Surgical resection coupled with adjuvant radiotherapy and/or doxorubicin based chemotherapy are the mainstays of synovial sarcoma (SS) treatment. Although effective as a SS adjuvant, the proposed mechanism of action of doxorubicin remains controversial. Current opinion supports DNA damage-induced apoptosis. This in vitro study used cDNA gene expression profiling to investigate whether apoptosis, alone or in combination with cell senescence, is induced by doxorubicin in SS cells. Cell cultures of the FU-SY-1 SS, the pleomorphic SW982 sarcoma, and a primary dermal fibroblast (NHDF), were exposed to 500 nM doxorubicin, and then processed for cDNA microarray analysis. The one class response option of SAM (Significance Analysis of Microarrays) was used to test for significant overexpression of 15 apoptosis-related genes and nine senescence-related genes. Drug-induced cell senescence was quantified by measuring beta-galactosidase activity. None of 15 apoptosis-related genes and only two of nine senescence-related genes were identified by SAM as significantly overexpressed in doxorubicin-treated cultures. Drug-induced senescence as reflected by beta-galactosidase activity was significantly increased (p < 0.05) only in FU-SY-1 SS cultures. Apoptosis does not appear to be a major determinant of doxorubicin-induced mortality in FU-SY-1 SS or NHDF cultures, but may impact SW982 cells via the overexpression of BAX relative to Bcl-2. Doxorubicin-induced cell senescence was prominent in FU-SY-1 SS cultures, but negligible in SW982 and NHDF cultures. Likely, both apoptosis and cell senescence contribute to doxorubicin-induced cell death in this synovial sarcoma cell line.
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PMID:Doxorubicin induces cell senescence preferentially over apoptosis in the FU-SY-1 synovial sarcoma cell line. 1670 98

Renal solitary fibrous tumors (SFTs) have been reported infrequently. We report a 76-year-old man with a left renal mass that had previously been shown radiographically to be stable, but was now growing. Grossly, the mass measured 12 cm, was poorly circumscribed, and invaded beyond the renal capsule. Approximately 10% of the neoplasm consisted of haphazardly arranged spindle cells admixed with dense collagenous bands, which is typical of benign SFT. However, the remainder of the mass was composed of pleomorphic, spindled sarcoma cells with frequent mitoses and foci of necrosis. Immunohistochemically, we observed CD34 labeling in the benign SFT component with loss of expression in the sarcomatous component, focal labeling for Bcl-2 protein in both areas, and absence of labeling for cytokeratin, renal cell carcinoma marker, S100 protein, CD117, and muscle markers in both areas. To our knowledge, this is the first reported case of malignant renal SFT, likely representing transformation from a histologically documented benign SFT component.
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PMID:Malignant solitary fibrous tumor of the kidney: report of a case and comprehensive review of the literature. 1674 40

We previously reported that wogonin, a flavonoid compound, was a potent apoptosis inducer of human hepatoma SMMC-7721 cells and murine sarcoma S180 cells. In the present study, the effect of oroxylin A, one wogonin structurally related flavonoid isolated from Scutellariae radix, on human hepatocellular carcinoma cell line HepG2 was examined and molecular mechanisms were also investigated. Oroxylin A inhibited HepG2 cell proliferation in a concentration- and time-dependent manner measured by MTT-assay. Treatment with an apoptosis-inducing concentration of oroxylin A caused typical morphological changes and apoptotic blebbing in HepG2 cells. DNA fragmentation assay was used to examine later apoptosis induced by oroxylin A. FACScan analysis revealed a dramatic increase in the number of apoptotic and G(2)/M phase arrest cells after oroxylin A treatment. The pro-apoptotic activity of oroxylin A was attributed to its ability to modulate the concerted expression of Bcl-2, Bax, and pro-caspase-3 proteins. The expression of Bcl-2 protein and pro-caspase-3 protein was dramatically decreased after treatment with oroxylin A. These results demonstrated that oroxylin A could effectively induce programmed cell death and suggested that it could be a promising antitumor drug.
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PMID:Oroxylin A induced apoptosis of human hepatocellular carcinoma cell line HepG2 was involved in its antitumor activity. 1706 58

Soft tissue sarcoma is a heterogeneous group of rare tumours arising predominantly from the embryonic mesoderm. While the prognosis is excellent for patients diagnosed at an early stage and treated by adequate surgery, unresectable or advanced metastatic diseases shrink the overall survival at 5 years dramatically to less than 10%. For metastatic soft tissue sarcoma, the armamentarium of effective chemotherapeutic agents is limited, especially when patients failed anthracycline- and/or ifosfamide-based chemotherapy. Fortunately, progress in the understanding of molecular biology and pathogenesis of soft tissue sarcomas has been made recently and should in the near future translate into molecular tumour characterization and the development of new therapeutic strategies. In this review, we briefly describe the status of current treatment strategies for soft tissue sarcoma. We will focus on the new and emerging compounds including recent developments of targeted therapy and cytotoxics such as antiangiogenic and immunomodulatory drugs, Bcl-2 antisense therapy, raf kinase inhibitors, heat shock protein modulators, anti-cytotoxic T lymphocyte-associated antigen (CTLA)-4 monoclonal antibody, proteasome inhibitors, minor groove binders, topoisomerase I inhibitors, and other agents being extensively developed in these solid tumours.
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PMID:Novel treatment strategies for soft tissue sarcoma. 1714 19

Sinus histiocytosis with massive lymphadenopathy (SHML) also called as Rosai Dorfman disease is a rare histiocytic proliferative disorder of unknown etiology. Histological features currently define it. Persistent painless lymphadenopathy due to expansion of sinuses infiltrated with benign histiocytes and plasma cells and emperipolesis are the characteristic features of SHML. Our study includes seven cases (5 nodal and 2 extranodal) of SHML over a 5-year period whose slides and blocks were reviewed. IHC was performed on the main lesion, from a panel of S100, CD68, LCA, CD20, CD3, CD30, CD43, bcl2, cytokeratin and epithelial membrane antigen. In our series we have work up available in 7 cases out of which a detailed follow-up is available in 5 patients. Out of these 5 patients, 4 have a stable disease, while one developed histiocytic sarcoma after a gap of four years.
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PMID:Sinus histiocytosis with massive lymphadenopathy--a review of seven cases. 1718 39

Liposarcoma, a malignancy of adipose tissue, is the most common soft tissue sarcoma. Patients whose primary tumor cannot be resected or those who have developed metastasis, have poor prognosis since liposarcomas are highly resistant to chemotherapy. We recently generated a spontaneously immortalized cell line, named LS14, from a patient with metastatic liposarcoma. Our goal was to compare the responsiveness of LS14 and SW872 liposarcoma cells to anti-cancer drugs and explore mechanisms of chemoresistance. Using complementary assays for cell viability and number we found that SW872 cells responded robustly to relatively low concentrations of doxorubicin, cisplatin and vinblastine. This reduction in cell viability was due to apoptosis, as evident by phosphatidylserine exposure and caspase 3 cleavage. In contrast, only a high dose of doxorubicin or combination therapy effectively reduced LS14 cell viability and induced apoptosis. LS14 cells showed a higher expression of Bcl-2 and Bcl-xL, but a lower expression of survivin and Bax, than SW872 cells, suggesting that anti-apoptotic proteins contribute to chemoresistance in LS14 cells. Although LS14 cells did not form colonies in soft agar, they generated large tumors and metastases in SCID mice, establishing their tumorigenicity in vivo. In conclusion, LS14 cells are much more resistant to chemotherapy than SW872 cells, making them an excellent model for exploring the efficacy and mechanism of action of anti-cancer drugs in liposarcomas.
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PMID:LS14 cells: a model for chemoresistance in liposarcoma. 1742 41

Utilizing melanoma and sarcoma tumor models syngeneic to C57BL/6 mice, we previously reported the antitumor effects of intratumoral (i.t.) administration of dendritic cells (DC) combined with localized radiotherapy (RT). However, the mechanisms underlying the augmented therapeutic effects have yet to be fully defined. Using the BALB/c host, we explored in this study the capacity of RT to augment the therapeutic efficacy of DC in the syngeneic renal cell cancer, Renca. I.t. DC administration combined with RT inhibited tumor growth in a synergistic manner. This extends our previous findings using a different host strain and two histologically distinct tumor models. More importantly, we provide evidence in this report that RT induced significant apoptosis and necrosis in Renca tumor cells, which involved down-regulated expression of Bcl-2 and a concurrent up-regulated expression of Bax. We also found significantly elevated expression of TNFalpha in RT plus DC-treated Renca tumors. Furthermore, splenocytes isolated from DC plus RT-treated mice elaborated higher levels of IL-2, IL-4, IFNgamma and IgG, IgM in response to tumor cells compared with splenocytes from monotherapy-treated hosts. These data support the conclusion that radiotherapy enhanced DC vaccination by inducing tumor cell apoptosis in BABL/c host, and the significantly augmented therapeutic efficacy by RT+DC treatment was associated with an increased local production of TNFalpha as well as an amplified systemic antitumor responses conferred by the combined therapy. I.t. DC administration in concert with localized RT may represent a promising novel regimen for human cancer therapy.
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PMID:Radiation-induced apoptosis along with local and systemic cytokine elaboration is associated with DC plus radiotherapy-mediated renal cell tumor regression. 1744 28

Tumor growth depends on 2 distinctive pathways: cell proliferation and apoptosis. The p53 pathway is an important regulator of the cell cycle as it triggers growth arrest or leads to apoptosis in response to cellular stress and therefore is commonly targeted during tumorigenesis. Apoptosis is also controlled by the Bcl-2 family, which includes proapoptotic and antiapoptotic proteins. The aim of this study was to investigate the expression of proteins that are involved in the p53 pathway and apoptosis in different types of soft tissue sarcomas and to correlate the expression of these proteins with the histologic grade of sarcoma cases. One hundred fifty-two cases of different types of soft tissue sarcomas were analyzed. The cases consisted of 54 low-grade, 40 intermediate-grade, and 58 high-grade sarcomas. Immunohistochemical stains for p21(WAF1/CIP1), p53, Mdm2, Bcl-2, and Bax proteins were carried out on tissue microarrays. Nuclear reactivity for p53 was detected in 49 cases (32.2%). Overexpression of Mdm2 was found in 18 cases (11.8%) and p21(WAF1/CIP1) immunostaining was seen in 28 tumors (18.4%). p53 and p21(WAF1/CIP1) expression correlated with the tumor grade (low grade, 5.6% and 3.7%; intermediate grade, 22.5% and 20%; high grade, 63.8% and 31%, respectively). Expression of Bax protein was a common finding in soft tissue sarcoma cases. It was detected in 141 cases (92.8%). Bcl-2 was identified in 59 tumors (38.8%) and was more prevalent in high-grade sarcomas (low grade, 25.9%; intermediate grade, 32.5%; high grade, 55.2%). It was concluded that alterations in the p53 pathway and genes that regulate apoptosis are common events in soft tissue sarcomas. The expression of p53, p21(WAF1/CIP1), and Bcl-2 is closely associated with the histologic grade of the tumor, and therefore these proteins may be used as prognostic markers.
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PMID:Immunoreactivity of p53, Mdm2, p21(WAF1/CIP1) Bcl-2, and Bax in soft tissue sarcomas: correlation with histologic grade. 1753 10

Soft tissue sarcomas are a heterogeneous group of tumours arising predominantly from the embryonic mesoderm. They account for less than 1% of all adult malignancies. The prognosis of patients with advanced metastatic soft tissue sarcoma remains poor with a disease-free survival at 5 years less than 10%. Despite improvements in local tumour control due to surgery and radiotherapy, distant metastasis and death remain a significant problem in 50% of patients. Complete resection remains the major factor in providing cure with limited benefits in local tumour control by radiotherapy and only minimal benefit of systemic therapy for metastatic disease. Only few chemotherapeutic agents have been identified to be active with reported response rates for doxorubicin and ifosfamide around 20%. New strategies are urgently needed to improve patients' outcome. Progress in the molecular characteristics, the understanding of biology and pathogenesis of these tumours has been made and should in the near future translate into molecularly based therapies. We describe current treatment strategies and existing standards. Moreover, we give an overview on the emerging compounds for patients with soft tissue sarcoma including recent developments of targeted therapy focusing on antiangiogenic and immunomodulatory drugs, Bcl-2 antisense therapy, raf kinase and mTOR inhibition, minor groove binders, and other agents being developed.
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PMID:Standards and novel therapeutic options in the treatment of patients with soft tissue sarcoma. 1847 6

Paclitaxel is a microtubule stabilizing drug that causes dividing cells to arrest and then undergo apoptosis. It also has antiangiogenic activity because it alters cytoskeletal structure, affecting migration and invasion. Paclitaxel is an effective treatment for AIDS-related Kaposi's sarcoma (KS). KS is a tumor in which there is marked proliferation of endothelial cells in addition to the tumor cells, which themselves share many markers with activated (proliferating) endothelial cells.We sought to determine the mechanism by which paclitaxel exerts its anti-KS tumor effects. In vitro, KS cells are very sensitive to paclitaxel, with half-maximal growth inhibition observed at 0.8 nM. Inhibition of migration of KS cells was also observed at nanomolar concentrations of the drug. Paclitaxel induced cell cycle arrest with an accumulation of cells in sub-G1.This was accompanied in vitro by various events typical of apoptosis: phosphorylation of two anti-apoptotic proteins Bcl-2 and Bcl-(xL) , release of cytochrome c into the cytoplasm, cleavage and activation of caspase-3. In vitro results were borne out by studies of KS tumor xenografts in nude mice. Paclitaxel (10 mg/kg) inhibited tumor growth by 75% over 21 days. Histological examination of the tumors revealed a decrease in proliferative index, a decrease in the number of mitotic figures and an increase in apoptotic cells compared to tumors from untreated mice.
Sarcoma 2000
PMID:Paclitaxel Induces Apoptosis in AIDS-Related Kaposi's Sarcoma Cells. 1852 33


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