tacrolimus and Carcinoma

Topics: Adenoma; Carcinoma; Humans; Neoplasms, Adnexal and Skin Appendage; Sebaceous Gland Neoplasms; Tacrolimus

Topics: Antifungal Agents; Antineoplastic Agents; Candidiasis; Carcinoma; Esophageal Neoplasms; Female; Humans; Immunosuppression Therapy; Kidney Transplantation; Middle Aged; Recurrence; Tacrolimus; Treatment Outcome

Topics: Administration, Topical; Adult; Calcineurin Inhibitors; Carcinoma; Dermatitis, Atopic; Humans; Keratinocytes; Skin Neoplasms; Tacrolimus

With this study we aimed to research the effects of immunosuppressive drugs, their cumulative doses, and viral infections on development of malign tumors in patients who have undergone treatment for 5 years.. We examined 100 patients who underwent renal transplantation from 2004 to 2009. Patients had mycophenolate mofetil and steroid in addition to cyclosporine, sirolimus, or tacrolimus as immunosuppressive treatment. For malignancy screening, physical examination, radiologic and endoscopic screening were done, and immunosuppressive drugs and their cumulative doses, age, sex, body mass index (BMI), dialysis history, and viral infection history were investigated.. The mean age of patients was 42.03 ± 11.30 years. There were 1 colon cancer patient, 1 retroperitoneal liposarcoma, 1 renal oncocytoma, 3 Kaposi sarcoma patients treated with cyclosporine; in those treated with Tac there were 1 basal cell carcinoma, 1 Kaposi sarcoma, 2 thyroid carcinoma, 1 breast carcinoma, 1 bladder carcinoma, 1 renal cell carcinoma, and 1 colon carcinoma patients. The mean age of patients having carcinoma was statistically significant compared with those without cancer (P < .01). The prednisolone cumulative dose was significantly higher in carcinoma patients than in patients without carcinoma (P < .01).. The use of long-term chronic immunosuppressive therapy may increase the development of cancer. The risk of carcinoma increases with increasing drug dose and time period of the immunosuppressive drug. There was not a negative effect on cancer prevalence in patients with cyclosporine or tacrolimus. But the cumulative dose of steroids significantly increased malignancy occurence.

Topics: Adult; Breast Neoplasms; Carcinoma; Colonic Neoplasms; Cyclosporine; Early Detection of Cancer; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; Mycophenolic Acid; Neoplasms; Retroperitoneal Neoplasms; Sarcoma, Kaposi; Sirolimus; Steroids; Tacrolimus; Thyroid Neoplasms; Time Factors; Urologic Neoplasms

To date, no study has compared the clinical characteristics, malignancy associations, and treatment of dermatomyositis in predominantly Caucasian vs. Asian populations.. This prospective study was conducted to compare clinical characteristics of dermatomyositis, its relationship to malignancy, and treatment between two tertiary medical centers in the USA and Singapore. A total of 19 newly-diagnosed patients in the USA and 15 patients in Singapore were enrolled. Dermatomyositis or amyopathic dermatomyositis were diagnosed based on clinical assessment, skin and muscle biopsies, and muscle testing.. Ninety-five percent of patients in the USA group were of Caucasian descent, while 93% of patients in the Singapore group were of Chinese descent. Both groups were predominantly female. Pruritus was the most common initial symptom reported in both groups, while periungual erythema and Gottron's papules were the most common skin presentations. Heliotrope eruption was more common in the Singapore group, occurring in 80% of patients vs. 32% of patients in the USA group (P = 0.007). Three patients in the Singapore group developed a malignancy, with two of these patients having nasopharyngeal carcinoma. None of the USA patients developed malignancies in a follow- up period of 2-5 years. Immunosuppressive steroid sparing therapy with hydroxychloroquine was more frequently used in Singapore, while topical tacrolimus was more frequently used in the USA.. The clinical presentations of dermatomyositis vary among different ethnic populations. Chinese patients with dermatomyositis have a significant risk for nasopharyngeal carcinoma.

Topics: Adrenal Cortex Hormones; Adult; Aged; Antibodies, Monoclonal, Murine-Derived; Asian People; Bone Density Conservation Agents; Calcium Compounds; Carcinoma; Dermatomyositis; Dietary Supplements; Diphosphonates; Erythema; Female; Humans; Hydroxychloroquine; Immunosuppressive Agents; Male; Methotrexate; Middle Aged; Mycophenolic Acid; Nasopharyngeal Neoplasms; Oxides; Prospective Studies; Pruritus; Rituximab; Singapore; Tacrolimus; Tertiary Care Centers; United States; Vitamin D; White People

Topics: Carcinoma; Demyelinating Diseases; Female; Humans; Immunosuppressive Agents; Liver Neoplasms; Magnetic Resonance Imaging; Middle Aged; Neurotoxicity Syndromes; Tacrolimus

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

The present study examines whether resistance to Cyclosporin A (CyA) and Tacrolimus (FK506) develops in T cells from individual patients and the role of P-glycoprotein 170 (P-gp) in mediating drug resistance. IC50s were established for CyA and FK506 in cell cultures from 46 renal allograft recipients. P-gp expression and functional activity were determined by flow cytometry. Mean ID50 for CyA was 29 microg/li (range 2.5-100) and for FK506 1.2 microg/li (range 0.085-5.5). The sensitivities to the two drugs were correlated (P = 0.0001). There was variation in the ratio of the ID50s depending on the drug used for treatment (P = 0.02). There was no difference in P-gp expression and functional activity in patients with sensitive or resistant cells. The data indicate an association between the sensitivities to CyA and FK506 and evidence of selective resistance to whichever drug was used. P-gp drug transport does not explain this variation.

Topics: Adult; Aged; ATP Binding Cassette Transporter, Subfamily B, Member 1; Breast Neoplasms; Calcineurin; Calcineurin Inhibitors; Carcinoma; Cells, Cultured; Cyclosporine; Cyclosporins; Drug Resistance; Drug Tolerance; Female; Humans; Immunosuppressive Agents; Kidney Transplantation; Male; Middle Aged; T-Lymphocytes; Tacrolimus; Tumor Cells, Cultured

T47D human breast carcinoma cells and the chicken oviduct were used to study the structure of the nonactivated progesterone receptor (PR) complex. Immunoprecipitation of PR (B form) from cytosol extracts was performed using monoclonal antibody PR6, a cross-reactive antibody prepared to chicken PR. Analysis of the PR complex by sodium dodecyl sulfate gels and Western immuno-blotting revealed the presence of several specific copurifying proteins. Consistent with previous reports, the two heat shock proteins, hsp90 and hsp70, were shown to be present. A third 59-kilodalton (kDa) protein observed previously was confirmed to be p59 (also called hsp56 or FKBP52), which has been shown to bind the immunosuppressant drug FK506. Two additional PR-associated proteins were observed that had not been previously recognized with human PR. These have molecular masses of 54-kDa and 23-kDa and have been shown by Western blotting to be related to the proteins p54 and p23 that are associated with chicken PR. P23 is a novel protein of unknown function and p54 or FKBP54 has been recently shown to be another FK506-binding protein related to p59. Finally, the cyclosporin A-binding protein, CyP-40, could be detected in isolated chicken PR complexes and in PR complexes that were reconstituted in vitro, but this protein was not detected in human PR complexes, which are less stable than chicken PR complexes in cytosol extracts. The functional significance of FK506 and cyclosporin A-binding proteins to hormone action was tested using a T47D cell line that contained a progestin reporter gene, MMTV-CAT. Treatment with cyclosporin A had no effect on the basal level of CAT expression, but it caused a dramatic increase in the sensitivity and magnitude of the response to the synthetic progestin, R5020. The enhanced response elicited by drug treatment was blocked by the antiprogestin RU486 indicating that this effect was receptor-mediated. While cyclosporin A enhanced progestin action in T47D cells, it inhibited a PR/reporter gene system in L cells. The drugs FK506 and rapamycin had no effect on progestin action in T47D cells, but they stimulated glucocorticoid action in T47D cells. Thus, the effects of these immunosuppressant drugs vary with the cell type and hormonal system that is tested. Whether these drug effects relate directly to the immunophilins bound in receptor complexes remains unknown.

Topics: Animals; Breast Neoplasms; Carcinoma; Carrier Proteins; Chickens; Cyclosporine; DNA-Binding Proteins; Gene Transfer Techniques; Heat-Shock Proteins; Humans; Immunosuppressive Agents; Mice; Receptor Aggregation; Receptors, Progesterone; Tacrolimus; Tacrolimus Binding Proteins; Tumor Cells, Cultured

A novel antitumor bicyclic depsipeptide, FR901228, was isolated from a broth culture of Chromobacterium violaceum No. 968 as colorless prisms and the molecular formula was determined as C24H36N4O6S2. This antibiotic reverted the transformed morphology of a Ha-ras transformant to normal, and exhibited prominent antitumor activities against murine and human tumor cell lines both in vitro and in vivo.

Topics: 3T3 Cells; Adenocarcinoma; Animals; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Carcinoma; Cell Line, Transformed; Chromobacterium; Depsipeptides; Drug Screening Assays, Antitumor; Female; Fermentation; Humans; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred C57BL; Mice, Inbred DBA; Mice, Nude; Microbial Sensitivity Tests; Neoplasm Transplantation; Peptides, Cyclic; Tacrolimus; Tumor Cells, Cultured