tacrolimus and Stomach-Neoplasms
tacrolimus has been researched along with Stomach-Neoplasms* in 4 studies
Other Studies
4 other study(ies) available for tacrolimus and Stomach-Neoplasms
Article | Year |
---|---|
mTOR signal and hypoxia-inducible factor-1 alpha regulate CD133 expression in cancer cells.
The underlying mechanism regulating the expression of the cancer stem cell/tumor-initiating cell marker CD133/prominin-1 in cancer cells remains largely unclear, although knowledge of this mechanism would likely provide important biological information regarding cancer stem cells. Here, we found that the inhibition of mTOR signaling up-regulated CD133 expression at both the mRNA and protein levels in a CD133-overexpressing cancer cell line. This effect was canceled by a rapamycin-competitor, tacrolimus, and was not modified by conventional cytotoxic drugs. We hypothesized that hypoxia-inducible factor-1 alpha (HIF-1 alpha), a downstream molecule in the mTOR signaling pathway, might regulate CD133 expression; we therefore investigated the relation between CD133 and HIF-1 alpha. Hypoxic conditions up-regulated HIF-1 alpha expression and inversely down-regulated CD133 expression at both the mRNA and protein levels. Similarly, the HIF-1 alpha activator deferoxamine mesylate dose-dependently down-regulated CD133 expression, consistent with the effects of hypoxic conditions. Finally, the correlations between CD133 and the expressions of HIF-1 alpha and HIF-1 beta were examined using clinical gastric cancer samples. A strong inverse correlation (r = -0.68) was observed between CD133 and HIF-1 alpha, but not between CD133 and HIF-1 beta. In conclusion, these results indicate that HIF-1 alpha down-regulates CD133 expression and suggest that mTOR signaling is involved in the expression of CD133 in cancer cells. Our findings provide a novel insight into the regulatory mechanisms of CD133 expression via mTOR signaling and HIF-1 alpha in cancer cells and might lead to insights into the involvement of the mTOR signal and oxygen-sensitive intracellular pathways in the maintenance of stemness in cancer stem cells. Topics: AC133 Antigen; Antigens, CD; Cell Line, Tumor; Chromones; Colorectal Neoplasms; Down-Regulation; Glycoproteins; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lung Neoplasms; Morpholines; Neoplasms; Peptides; Protein Kinases; RNA, Messenger; Signal Transduction; Sirolimus; Stomach Neoplasms; Tacrolimus; TOR Serine-Threonine Kinases; Transcription, Genetic; Up-Regulation | 2009 |
Esophageal squamous cell carcinoma after liver transplantation.
The occurrence of an oesophageal squamous cell carcinoma following liver transplantation is very infrequent. Such an event has been related to a history of alcohol-induced cirrhosis, as in other squamous cell tumours of the oropharynx. We report the case of a 64-year-old male patient diagnosed as having oesophageal squamous cell carcinoma six years after having had a liver transplant due to alcohol-induced cirrhosis. The tumour was treated surgically and consisted of an Ivor-Lewis oesophagectomy. The patient is disease-free 17 months after surgery. A review of the cases reported in the literature indicated treatment with chemotherapy and radiation therapy, and with excision in some cases. Generally, despite aggressive treatment the prognosis is poor. Topics: Alcoholism; Carcinoma, Squamous Cell; Cardia; Deglutition Disorders; Esophageal Neoplasms; Esophageal Stenosis; Esophagectomy; Humans; Immunocompromised Host; Immunosuppression Therapy; Immunosuppressive Agents; Liver Cirrhosis, Alcoholic; Liver Transplantation; Male; Middle Aged; Neoplasms, Multiple Primary; Postoperative Complications; Remission Induction; Stomach Neoplasms; Tacrolimus | 2005 |
Inhibition of interferon-gamma-activated nuclear factor-kappa B by cyclosporin A: A possible mechanism for synergistic induction of apoptosis by interferon-gamma and cyclosporin A in gastric carcinoma cells.
We previously reported synergistic induction of apoptosis by IFN-gamma plus either cyclosporin A (CsA) or tacrolimus (FK506) in gastric carcinoma cells. In this study, we aimed to elucidate the mechanism for this synergistic induction of apoptosis. IFN-gamma plus CsA synergistically induced caspase-3 mediated apoptosis in gastric carcinoma cells. Although IFN-gamma induced activation of signal transducer and activator of transcription1 (STAT1) and expression of interferon regulatory factor-1 (IRF-1) mRNA, IFN-gamma alone was not able to induce caspase-3 activation and apoptosis. When gastric carcinoma cells were treated with cyclohexamide, a protein synthesis inhibitor, following IFN-gamma pretreatment, caspase-3 was activated, and apoptosis was markedly induced. These findings suggest the existence of IFN-gamma-induced anti-apoptotic pathway and we evaluated the effect of IFN-gamma and CsA on calcium-sensitive nuclear factor-kappa B (NF-kappa B) activation. IFN-gamma increased intracellular calcium ion concentration ([Ca(2+)](i)) consisting of a spike and a sustained phase, and the latter was completely abrogated by CsA. Activation of NF-kappa B occurred in response to IFN-gamma, and which was markedly inhibited by either CsA or FK506. NF-kappa B decoy also enhanced the cytotoxic effect of IFN-gamma. These results suggest that IFN-gamma may simultaneously induce the STAT1-mediated apoptotic pathway and the anti-apoptotic pathway through calcium-activated NF-kappa B and that inhibition of the latter by CsA may result in dominance of the apoptosis-inducing pathway. Topics: Antineoplastic Agents; Apoptosis; Calcium; Carcinoma; Caspase 3; Caspases; Cycloheximide; Cyclosporine; DNA-Binding Proteins; Drug Synergism; Humans; Interferon Regulatory Factor-1; Interferon-gamma; Models, Biological; NF-kappa B; Phosphoproteins; Protein Synthesis Inhibitors; RNA, Messenger; STAT1 Transcription Factor; Stomach Neoplasms; Tacrolimus; Trans-Activators; Tumor Cells, Cultured | 2003 |
The role of endogenous interleukin-2 in proliferation of human carcinoma cell lines.
Interleukin (IL-2) and IL-2Rbeta/gamma have been shown to be expressed in human carcinomas in culture and in situ. Recently, expression of endogenous IL-2 and IL-2R in the cytoplasm was found to be up-regulated in tumour cells undergoing mitosis. This observation suggested that similar to its role in lymphocytes, the IL-2/IL-R pathway is involved in the regulation of carcinoma cell proliferation. Metabolic labelling followed by immunoprecipitation and Western blot results showed that IL-2 in carcinomas was identical to that in human lymphocytes. However, tumour cells did not secrete IL-2 detectable by immunoassays, although membrane-associated IL-2 was detectable on a proportion of these cells cultured in the absence of exogenous IL-2. Antibodies to IL-2 failed to inhibit proliferation of carcinoma cells, but antibodies specific for the ligand-binding site of the IL-2R were growth inhibitory. Growth of tumour cells was also inhibited by the immunosuppressive drugs, cyclosporin A (CsA), FK506 and rapamycin (RPA), known to interfere with the IL-2 pathway in lymphocytes. To further confirm the role of endogenous IL-2 in the growth of carcinomas, tumour cells were incubated with an IL-2-specific antisense oligonucleotide. The treatment was shown to transiently inhibit IL-2 mRNA and IL-2 protein expression as well as proliferation of tumour cells. Tumour cells treated with IL-2-specific antisense oligonucleotide demonstrated increased apoptosis in comparison to untreated or sense oligonucleotide-treated control cells. The data indicate that in human carcinomas, endogenous IL-2 promotes growth and protects tumour cells from apoptosis. Topics: Antibodies; Apoptosis; Carcinoma, Squamous Cell; Cell Division; Head and Neck Neoplasms; Humans; Interleukin-2; Jurkat Cells; Oligonucleotides, Antisense; Receptors, Interleukin-2; Sirolimus; Stomach Neoplasms; Tacrolimus; Tumor Cells, Cultured | 1999 |