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)

We report a case of solitary fibrous tumor involving the spinal nerve root at the L1-L2 level in a 67-year-old man. The patient presented with lumbar pain and weakness in his right lower extremity. Histologically, the tumor was composed of a proliferation of monomorphous spindle cells in an abundant collagenous stroma; neither necrosis nor mitoses were evident. These cells were strongly immunoreactive with CD34, Bcl-2, CD99, and vimentin, but were negative with S100 protein, smooth muscle actin, and epithelial membrane antigen. Such an immunohistochemical profile was consistent with a solitary fibrous tumor of the spinal nerve rootlet and ruled out the main differential diagnoses, schwannoma and meningioma. The present case suggests that solitary fibrous tumor should be considered in differentiating spindle cell lesions of the spinal cord and nerve rootlet.
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PMID:Solitary fibrous tumor of the spinal nerve rootlet: report of a case mimicking schwannoma. 1498 50

Androgen-deprivation therapy, usually with combined androgen blockade, is standard initial treatment for advanced prostate cancer. With failure of initial treatment, as indicated by rising prostate-specific antigen (PSA) levels, second-line hormonal therapy is usually instituted. Over the past several years, it has become increasingly clear that systemic chemotherapy has an important role in hormone-refractory disease. Phase II trials have demonstrated high PSA and measurable disease response rates with taxane single-agent and combination treatments. One recent phase III trial showed that docetaxel (Taxotere)/ estramustine (Emcyt) significantly improved overall survival, progression-free survival, and PSA response rate compared with mitoxantrone (Novantrone) plus prednisone. Another phase III trial demonstrated that docetaxel given every 3 weeks plus prednisone significantly improved overall survival, PSA response rate, pain relief response rate, and quality of life compared with mitoxantrone and prednisone. On the basis of these findings, every-3-week docetaxel plus prednisone is now considered standard first-line therapy for metastatic hormone-refractory disease. There is considerable optimism that treatment can be further improved. Studies of taxane combinations with bevacizumab (Avastin), thalidomide (Thalomid), bortezomib (Velcade), antisense Bcl-2 oligonucleotide, mTOR inhibitors, epidermal growth factor receptor inhibitors, and KDR inhibitors are under way. Randomized phase III trials in progress or planned are examining docetaxel in combination with imatinib mesylate (Gleevec) or calcitriol and docetaxel/prednisone in combination with bevacizumab and an antisense clusterin compound. Other promising systemic agents include epothilones and atrasentan, and promising vaccines include Provenge, GVAX, and Prostvac.
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PMID:Recent progress in management of advanced prostate cancer. 1594 43

The taxoid analogue docetaxel is a potent inhibitor of microtubular depolymerisation and, in hormone-refractory metastatic prostate cancer, it also counters the effects of the anti-apoptotic protein Bcl-2. Overall survival was significantly increased in patients with hormone-refractory metastatic prostate cancer receiving intravenous docetaxel every 3 weeks plus oral prednisone or estramustine, compared with patients receiving intravenous mitoxantrone every 3 weeks plus prednisone in two large phase III trials (TAX 327 and SWOG [Southwest Oncology Group] 9916). In the TAX 327 study, patients receiving docetaxel 75 mg/m(2) every 3 weeks plus prednisone had a median overall survival duration of 18.9 months; in the SWOG 9916 study, median overall survival duration was 17.5 months with docetaxel 60 mg/m(2) every 3 weeks plus estramustine 280 mg three times daily on days 1-5. The median overall survival duration for the control arm of mitoxantrone 12 mg/m(2) every 3 weeks plus prednisone was 16-17 months. Compared with mitoxantrone plus prednisone, docetaxel plus prednisone improved prostate specific antigen response rate, pain and health-related quality of life, and docetaxel plus estramustine increased progression-free survival. Adverse events were more common with docetaxel- than mitoxantrone-based treatment regimens, but most events associated with docetaxel were mild-to-moderate in severity.
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PMID:Docetaxel in hormone-refractory metastatic prostate cancer. 1626 95

Prostate cancer is one of the most common non-skin cancers in men. Amygdalin is one of the nitrilosides, natural cyanide-containing substances abundant in the seeds of plants of the prunasin family that have been used to treat cancers and relieve pain. In particular, D-amygdalin (D-mandelonitrile-beta-D-gentiobioside) is known to exhibit selective killing effect on cancer cells. Apoptosis, programmed cell death, is an important mechanism in cancer treatment. In the present study, we prepared the aqueous extract of the amygdalin from Armeniacae semen and investigated whether this extract induces apoptotic cell death in human DU145 and LNCaP prostate cancer cells. In the present results, DU145 and LNCaP cells treated with amygdalin exhibited several morphological characteristics of apoptosis. Treatment with amygdalin increased expression of Bax, a pro-apoptotic protein, decreased expression of Bcl-2, an anti-apoptotic protein, and increased caspase-3 enzyme activity in DU145 and LNCaP prostate cancer cells. Here, we have shown that amygdalin induces apoptotic cell death in human DU145 and LNCaP prostate cancer cells by caspase-3 activation through down-regulation of Bcl-2 and up-regulation of Bax. The present study reveals that amygdalin may offer a valuable option for the treatment of prostate cancers.
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PMID:Amygdalin induces apoptosis through regulation of Bax and Bcl-2 expressions in human DU145 and LNCaP prostate cancer cells. 1688 Jun 11

Morphine is recommended as a first-line opioid analgesic in the pain management of cancer patients. Accumulating evidence shows that morphine has anti-apoptotic activity, but its impact on the therapeutic applications of antineoplastic drugs is not well known. The present study was undertaken to test the hypothesis that morphine might antagonize the pro-apoptotic activity of DOX (doxorubicin), a commonly used antitumour drug for the treatment of neuroblastoma, in cultured SH-SY5Y cells. In the present study we demonstrated that morphine suppressed DOX-induced inhibition of cell proliferation and programmed cell death in a concentration-dependent, and naloxone as well as pertussis toxin-irreversible, manner. Further studies showed that morphine inhibited ROS (reactive oxygen species) generation, and prevented DOX-mediated caspase-3 activation, cytochrome c release and changes of Bax and Bcl-2 protein expression. The antioxidant NAC (N-acetylcysteine) also showed the same effects as morphine on DOX-induced ROS generation, caspase-3 activation and cytochrome c release and changes in Bax (Bcl-2-associated X protein) and Bcl-2 protein expression. Additionally, morphine was found to suppress DOX-induced NF-kappaB (nuclear factor kappaB) transcriptional activation via a reduction of IkappaBalpha (inhibitor of nuclear factor kappaB) degradation. These present findings support the hypothesis that morphine can inhibit DOX-induced neuroblastoma cell apoptosis by the inhibition of ROS generation and mitochondrial cytochrome c release, as well as by blockade of NF-kappaB transcriptional activation, and suggests that morphine might have an impact on the antitumour efficiency of DOX.
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PMID:Morphine inhibits doxorubicin-induced reactive oxygen species generation and nuclear factor kappaB transcriptional activation in neuroblastoma SH-SY5Y cells. 1754 80

Glioblastoma patients receive anti-inflammatory agent for alleviation of vasogenic edema and pain prior to surgery, radiotherapy, and chemotherapy. Oxidative stress is an important mechanism of action of some chemotherapeutic agents in the treatment of glioblastoma. So, we examined the modulatory effects of methylprednisolone (MP, a steroidal anti-inflammatory agent) and indomethacin (IM, a non-steroidal anti-inflammatory agent) on apoptosis in rat C6 glioblastoma cells following oxidative stress with hydrogen peroxide (H(2)O(2)). Exposure of C6 cells to 1 mM H(2)O(2) for 24 h caused significant amounts of morphological and biochemical features of apoptosis. Expressions of Bax and Bcl-2 at mRNA and protein levels were altered resulting in an increase in Bax : Bcl-2 ratio in apoptotic cells, which also exhibited overexpression of 80 kDa calpain and an increase in calpain-cleaved 145 kDa alpha-spectrin breakdown product. Immunofluorescent and propidium iodide labeling detected caspase-3-p20 fragment in apoptotic cells, indicating activation of caspase-3 as well. Treatment of cells with 1 microM MP or 10 microM IM alone did not induce apoptosis. Pretreatment (1 h) with either 1 microM MP or 10 microM IM significantly inhibited H(2)O(2) mediated apoptosis in C6 cells. Thus, pretreatment of glioblastoma with an anti-inflammatory agent, either steroidal or non-steroidal, may compromise the action of a chemotherapeutic agent that mediates therapeutic action via oxidative stress.
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PMID:Methylprednisolone and indomethacin inhibit oxidative stress mediated apoptosis in rat C6 glioblastoma cells. 1757 61

Chronic pain has been reported to induce apoptosis. Both chronic excitation of neural pathways involved in pain transmission and control and the stress of pain may be potentially involved in apoptosis induced by pain. Here, we have investigated their possible role in pain-induced apoptosis. Inflammatory pain was induced by injection of formalin in intact and adrenalectomized (ADX) rats. Following exposure to repeated injections of 5% formalin, we detected Bax, Bcl-2, pro-caspase and activated caspase-3 proteins using immunoblotting. The results were compared with those obtained from animals suffered from chronic immobilization stress (IMO). These results showed an increased ratio of Bax/Bcl-2 and activated caspase-3 in hippocampus and dorsal lumbar spinal cord of animals treated with pain and IMO stress; these effects were reduced in ADX animals. On the other hand, the remaining apoptotic effect of pain in adrenalectomized rats was also significant. We surmise that both chronic neural activation and the stress induced by pain are involved in pain-induced apoptosis.
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PMID:Stress- and non-stress-mediated mechanisms are involved in pain-induced apoptosis in hippocampus and dorsal lumbar spinal cord in rats. 1882 55

Prostate cancer (PCA) is the most common invasive malignancy and the second leading cause of cancer-related death in males. The present study investigated the effects of fangchinoline (Fan), an important compound in Stephania Tetradra S. Moore (Fenfangji) with pain-relieving, blood pressure-depressing, and antibiotic activities, on human PCA. It was found that Fan inhibited human prostate cancer cell lines (PC3) cell proliferation in a dose- and time-dependent manner. Studies of cell-cycle progression showed that the anti-proliferative effect of Fan was associated with an increase in the G1/S phase of PC3 cells. Western blot results indicated that Fan-induced G1/S phase arrest was mediated through inhibition of cyclin-regulated signaling pathways. Fan induced p27 expression and inhibited cyclin D and proliferating cell nuclear antigen (PCNA) expression in PC3 cells. Increased exposure time to Fan caused apoptosis of PC3 cells, which was associated with up-regulation of pro-apoptotic proteins Bax and caspase 3, and down-regulation of anti-apoptotic protein Bcl-2. Furthermore, Fan had anti-tumorigenic activity in vivo, including reduction of tumor volume and pro-apoptotic and anti-proliferative effects in a PC3 nude mouse xenograft. Taking all this together, it can be concluded that Fan is an effective anti-proliferative agent that modulates cell growth regulators in prostate cancer cells.
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PMID:Fangchinoline induced G1/S arrest by modulating expression of p27, PCNA, and cyclin D in human prostate carcinoma cancer PC3 cells and tumor xenograft. 2020 55

Tolerance to the chronic administration of opioids such as morphine reduces the utility of these drugs in pain management. Despite significant investigation, the precise cellular mechanisms underlying opioid tolerance and dependence remain elusive. It has been indicated that tolerance to the analgesic effect of morphine is associated with apoptosis in the central nervous system. The aim of this study was to examine the effects of the intracerebroventricular (icv) administration of minocycline (a second-generation tetracycline) on morphine-induced apoptosis in the cerebral cortex and lumbar spinal cord of rats after morphine-induced tolerance. Different groups of rats received either morphine (ip) and distilled water (icv) or morphine and different doses of minocycline (icv) or minocycline alone once per day. The terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) method was used to analyze apoptosis. The anti-apoptotic factors, Bcl-2 and HSP 70 and the pro-apoptotic element caspase-3 were evaluated by immunoblotting. The results indicated that minocycline attenuated the number of apoptotic cells in both the cerebral cortex and lumbar spinal cord. Immunoblotting findings showed that the amounts of anti-apoptotic agents (Bcl-2 and HSP 70) were greater in the treatment groups than in the controls in both regions. Although minocycline did not change the level of caspase-3 at the doses used with morphine but the minocycline treated rats showed a significantly lower increase in caspase-3 activity than did in the control. In conclusion, minocycline decreased the number of TUNEL-positive cells and increased the amount of anti-apoptotic factors (Bcl-2 and HSP 70), but did not change the caspase-3 content.
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PMID:Minocycline prevents morphine-induced apoptosis in rat cerebral cortex and lumbar spinal cord: a possible mechanism for attenuating morphine tolerance. 2071 99

Opiates are the most effective drugs for pain relief. However, the repeated use of opiates induces tolerance to their analgesic effects. It has been shown that this morphine-induced tolerance is associated with apoptosis in the central nervous system. The aim of this study is to evaluate the effects of intracerebroventricular (i.c.v.) administration of riluzole, an anti-glutamatergic drug, on morphine-induced apoptosis in the lumbar region of the rat spinal cord. Animals were given daily injections of morphine and vehicle, morphine and riluzole, or riluzole alone. Nociception was assessed using a hot plate apparatus, and apoptosis was assessed using the in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method. The levels of anti-apoptotic factors Bcl-2 and HSP 70 and the pro-apoptotic agent caspase-3 were evaluated using immunoblotting. The glutamate concentration in the lumbar spinal cord was measured with high performance liquid chromatography (HPLC). The results indicate that the i.c.v. administration of riluzole attenuated morphine tolerance and reduced the number of TUNEL positive cells. Immunoblotting revealed that the levels of the selected anti-apoptotic agents were greater in the treatment groups compared to the controls. Furthermore, the results demonstrated that the administration of riluzole can attenuate the morphine-induced elevation of glutamate in the lumbar spinal cord. In conclusion, i.c.v. administration of riluzole attenuated morphine-induced tolerance to analgesia and apoptosis in addition to preventing the morphine-induced increase of glutamate in the lumbar spinal cord of rats.
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PMID:Intracerebroventricular administration of riluzole prevents morphine-induced apoptosis in the lumbar region of the rat spinal cord. 2088 6


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