Switch to a Sirolimus‐Based Immunosuppression in Long‐Term Renal Transplant Recipients: Reduced Rate of (Pre‐)Malignancies and Nonmelanoma Skin Cancer in a Prospective, Randomized, Assessor‐Blinded, Controlled Clinical Trial

Salgo, Rebekka; Goßmann, Jan; Schöfer, Helmut; Kachel, Heinz-Georg; Kuck, Joachim; Geiger, Helmut; Kaufmann, R.; Scheuermann, Ernst-Heinrich

doi:10.1111/j.1600-6143.2009.02997.x

Cited by 202 publications

(152 citation statements)

References 35 publications

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“…By inhibiting mTOR, rapamycin inhibits the transduction of microenvironmental signals, including cytokines, and abrogates cell proliferation and protein synthesis in immune cells, thus inhibiting immune responses (11). Rapamycin was first used as an immunosuppressive drug in combination with cyclosporine and was shown to decrease the risk of posttransplant malignancies (36,37) due to its properties as an inhibitor of cancer cell proliferation, leading to its use in cancer therapies.…”

Section: Discussionmentioning

confidence: 99%

Rapamycin Impairs Antitumor CD8+ T-cell Responses and Vaccine-Induced Tumor Eradication

et al. 2015

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The metabolic sensor mTOR broadly regulates cell growth and division in cancer cells, leading to a significant focus on studies of rapamycin and its analogues as candidate anticancer drugs. However, mTOR inhibitors have failed to produce useful clinical efficacy, potentially because mTOR is also critical in T cells implicated in immunosurveillance. Indeed, recent studies using rapamycin have demonstrated the important role of mTOR in differentiation and induction of the CD8 þ memory in T-cell responses associated with antitumor properties.

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Section: Discussionmentioning

confidence: 99%

Rapamycin Impairs Antitumor CD8+ T-cell Responses and Vaccine-Induced Tumor Eradication

et al. 2015

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“…Whether this effect is related to the rapamycin-induced increase in apoptotic responses we have observed after UV irradiation (21), is not clear. From a clinical perspective, recent trials do suggest rapamycin treatment decreases the development of skin carcinomas in organ transplant recipients (22,23).…”

Section: Introductionmentioning

confidence: 99%

Dietary Immunosuppressants Do Not Enhance UV-Induced Skin Carcinogenesis, and Reveal Discordance between p53-Mutant Early Clones and Carcinomas

Voskamp

Bodmann

Koehl

et al. 2013

Cancer Prevention Research

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Immunosuppressive drugs are thought to cause the dramatically increased risk of carcinomas in sunexposed skin of organ transplant recipients. These drugs differ in local effects on skin. We investigated whether this local impact is predictive of skin cancer risk and may thus provide guidance on minimizing the risk. Immunosuppressants (azathioprine, cyclosporine, tacrolimus, mycophenolate mofetil, and rapamycin) were assessed on altering the UV induction of apoptosis in human skin models and of p53 mutant cell clones (putative tumor precursors) and ensuing skin carcinomas (with mutant p53) in the skin of hairless mice. Rapamycin was found to increase apoptosis (three-fold), whereas cyclosporine decreased apoptosis (three-fold). Correspondingly, a 1.5-to five-fold reduction (P ¼ 0.07) or a two-to three-fold increase (P < 0.001) was found in cell clusters overexpressing mutant p53 in chronically UV-exposed skin of mice that had been fed rapamycin or cyclosporine, respectively. Deep sequencing showed, however, that the allelic frequency ($5%) of the hotspot mutations in p53 (codons 270 and 275) remained unaffected. The majority of cells with mutated p53 seemed not to overexpress the mutated protein. Unexpectedly, none of the immunosuppressants admixed in high dosages to the diet accelerated tumor development, and cyclosporine even delayed tumor onset by approximately 15% (P < 0.01). Thus, in contrast to earlier findings, the frequency of p53-mutant cells was not predictive of the incidence of skin carcinoma. Moreover, the lack of any accelerative effect on tumor development suggests that immunosuppressive medication is not the sole cause of the dramatic increase in skin cancer risk in organ transplant recipients. Cancer Prev Res; 6(2);

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“…Changing azathioprine to rapamycin may ameliorate the skin cancers (32). However, there is a significant risk of worsening proteinuria and inducing graft dysfunction, especially in this patient with proteinuria and recurrent membranous.…”

Section: Discussion Of Question 2bmentioning

confidence: 99%

American Society of Nephrology Quiz and Questionnaire 2012

Brennan

Glassock

Bleyer

2013

Clinical Journal of the American Society of Nephrology

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SummaryPresentation of the Nephrology Quiz and Questionnaire has become an annual tradition at the meetings of the American Society of Nephrology. It is a very popular session, as judged by consistently large attendance. Members of the audience test their knowledge and judgment on a series of case-oriented questions prepared and discussed by experts. They can also compare their answers in real time, using audience response devices, to those of program directors of nephrology training programs in the United States, acquired through an Internet-based questionnaire. Topics presented here include fluid and electrolyte disorders, transplantation, and ESRD and dialysis. Cases representing each of these categories, along with single-best-answer questions, were prepared by a panel of experts (Drs. Palmer, Fervenza, Brennan, and Mehrotra, respectively). The correct and incorrect answers were briefly discussed after the audience responses, and the results of the questionnaire were displayed. This article recapitulates the session and reproduces its educational value for a larger audience-that of the readers of the Clinical Journal of the American Society of Nephrology. Have fun.Clin J Am Soc Nephrol 8: 1267-1272, 2013. doi: 10.2215/CJN.00430113Transplantation Case 1A 51-year-old man with ESRD from IgA nephropathy received a one-haplotype matched living-related transplant from his brother. The baseline panel-reactive antibody level was 0%, and both donor and recipient were cytomegalovirus (CMV) seropositive. Induction immunosuppression included 1 mg/kg rabbit antithymocyte globulin (r-ATG) initiated intraoperatively, 2 mg/kg r-ATG given postoperatively on days 1 and 2, and 500 mg methylprednisolone. The recipient's maintenance immunosuppression consists of tacrolimus (trough, 7 ng/dl); enteric mycophenolic acid salt, 360 mg twice daily; and prednisone, 5 mg daily. He presents 25 days after transplantation with acute onset of fever, jaw pain, and bilateral hip and shoulder pain. He is receiving prophylactic trimethoprimsulfamethoxazole, 400/800 mg/d, and valganciclovir, 450 mg/d. He also takes clopidogrel for a history of coronary artery disease, status post drug-eluting stent placement. He had a history of raising, hunting, and ingesting rabbits.The physical examination findings include a body temperature of 36.5°C, BP of 134/84 mmHg, no graft tenderness, and pain and limited range of motion of the affected joints. The patient has a functioning left CiminoBrescia fistula. His baseline serum creatinine level is 1.5 mg/dl, with an estimated GFR of 58 ml/min per 1.73 m 2

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Switch to a Sirolimus‐Based Immunosuppression in Long‐Term Renal Transplant Recipients: Reduced Rate of (Pre‐)Malignancies and Nonmelanoma Skin Cancer in a Prospective, Randomized, Assessor‐Blinded, Controlled Clinical Trial

Cited by 202 publications

References 35 publications

Rapamycin Impairs Antitumor CD8+ T-cell Responses and Vaccine-Induced Tumor Eradication

Rapamycin Impairs Antitumor CD8+ T-cell Responses and Vaccine-Induced Tumor Eradication

Dietary Immunosuppressants Do Not Enhance UV-Induced Skin Carcinogenesis, and Reveal Discordance between p53-Mutant Early Clones and Carcinomas

American Society of Nephrology Quiz and Questionnaire 2012

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