Renal cancer in kidney transplanted patients

Frascà, Giovanni M.; Cosmai, Laura; Porta, Camillo; Asch, William S.; Santoni, Matteo; Salviani, Chiara; d’Errico, Angelo; Malvi, Deborah; Balestra, Emilio; Gallieni, Maurizio

doi:10.1007/s40620-015-0219-8

Cited by 41 publications

(38 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…c-Met-mediated Ras activation plays a major role in the accelerated growth of renal cancer, which is also a critical problem in immuno-suppressed patients 4, 19, 21, 24 . Here, we report that HNK can effectively inhibit c-Met-mediated growth promoting pathways in RCC, involving the cytoprotective molecule HO-1.…”

Section: Discussionmentioning

confidence: 99%

“…Also, there is an unmet need to identify novel therapeutic drugs/approaches to effectively suppress CNI-induced tumor growth 19 . HNK is one such promising drug with both chemopreventive and anti-inflammatory properties 1 ; therefore, the use of HNK as a therapeutic for patients after organ transplantation can potentially have dual benefit, i.e.…”

Section: Discussionmentioning

confidence: 99%

“…Although aberrant c-Met and other RTK hyper-activation are the major drivers of renal cancer growth, recent reports clearly suggest an alarmingly high incidence of renal cancer in patients receiving calcineurin inhibitors (CNIs) as immunosuppressive therapy for the treatment of immune disorders or after having organ transplants 19–21 . The CNI Cyclosporine A (CsA) inhibits T cell activation, by down-regulating the phosphatase activity of calcineurin and preventing the nuclear translocation of NFAT, a crucial factor for T cell activation, and thereby suppresses immune system 22 .…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Honokiol inhibits c-Met-HO-1 tumor-promoting pathway and its cross-talk with calcineurin inhibitor-mediated renal cancer growth

Balan

Chakraborty

Flynn

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Honokiol (HNK) is a small molecule with potent anti-inflammatory and anti-tumorigenic properties; yet the molecular targets of HNK are not well studied. Hyperactivation of the receptor tyrosine kinase c-Met and overexpression of the cytoprotective enzyme heme oxygenase-1 (HO-1) play a critical role in the growth and progression of renal cell carcinoma (RCC). Interestingly, the calcineurin inhibitor (CNI) cyclosporine A (CsA), an immunosuppressant used to prevent allograft rejection, can also increase the risk of RCC in transplant patients. We studied the potential role of c-Met signaling axis on CNI-induced renal tumor growth and tested the anti-tumor efficacy of HNK. Importantly, CNI treatment promoted c-Met induction and enhanced c-Met-induced Ras activation. We found that HNK treatment effectively down-regulated both c-Met phosphorylation and Ras activation in renal cancer cells. It inhibited the expression of both c-Met- and CNI-induced HO-1, and promoted cancer cell apoptosis. In vivo, HNK markedly inhibited CNI-induced renal tumor growth; and it decreased the expression of phospho-c-Met and HO-1 and reduced blood vessel density in tumor tissues. Our results suggest a novel mechanism(s) by which HNK exerts its anti-tumor activity through the inhibition of c-Met-Ras-HO-1 axis; and it can have significant therapeutic potential to prevent post-transplantation cancer in immunosuppressed patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Honokiol inhibits c-Met-HO-1 tumor-promoting pathway and its cross-talk with calcineurin inhibitor-mediated renal cancer growth

Balan

Chakraborty

Flynn

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…Goh et al recommended screening ultrasound every 2 years for patients with ACKD and every 5 years for recipients without ACKD . Frasca et al proposed annual screening ultrasound for patients with ADPKD or ACKD and every 2 years for patients older than 60 years who had been receiving dialysis longer than 5 years before transplantation …”

Section: Renal Cell Carcinomamentioning

confidence: 99%

Urologic malignancies in kidney transplantation

Hickman

Sawinski

Guzzo

et al. 2018

American Journal of Transplantation

View full text Add to dashboard Cite

With advances in immunosuppression, graft and patient outcomes after kidney transplantation have improved considerably. As a result, long-term complications of transplantation, such as urologic malignancies, have become increasingly important. Kidney transplant recipients, for example, have a 7-fold risk of renal cell carcinoma (RCC) and 3-fold risk of urothelial carcinoma (UC) compared with the general population. While extrapolation of data from the general population suggest that routine cancer screening in transplant recipients would allow for earlier diagnosis and management of these potentially lethal malignancies, currently there is no consensus for posttransplantation RCC or UC screening as supporting data are limited. Further understanding of risk factors, presentation, optimal management of, and screening for urologic malignancies in kidney transplant patients is warranted, and as such, this review will focus on the incidence, surveillance, and treatment of urologic malignancies in kidney transplant recipients.

show abstract

“…However, considering that transplanted patients inherently have an increased risk of cancer when compared with the general population, mainly due to prolonged immunosuppressive therapy [6], they should be evaluated carefully before listing, in order to avoid first of all the risk of worsening the patient prognosis instead of improving it, and secondly the use of a scarce resource, such as donated organs, for subjects with a limited life span.…”

Section: Introductionmentioning

confidence: 99%

Kidney transplantation in patients with previous renal cancer: a critical appraisal of current evidence and guidelines

et al. 2018

Self Cite

View full text Add to dashboard Cite

Due to the increasing occurrence of renal cell carcinoma (RCC) in the general population and the high prevalence of chronic kidney disease among cancer patients, many people with a previous RCC are considered as potential candidates for renal transplantation. They should accordingly be evaluated to assess their life expectancy and the risk that the chronic immunosuppressive therapy needed after grafting might impair their long-term outcome.Current guidelines on listing patients for renal transplantation suggest that no delay is required for subjects with small or incidentally discovered RCC, while the recommendations for patients who have been treated for a symptomatic RCC or for those with large or invasive tumours are conflicting.The controversial results reported by even recent studies focussing on the cancer risk in kidney graft recipients with a prior history of malignancy do not help to clarify the doubts arising in everyday clinical practice.Several tools, including integrated scoring systems, are currently available to assess the prognosis of patients with a previous RCC and, although they have not been validated in subjects receiving long-term immunosuppressive drugs, they can be used to identify patients suitable to be listed for grafting. Among these, the Leibovich score is currently the most widely used as it has proved simple and reliable enough and helps categorize renal transplant candidates. According to this system, subjects with a score from 0 to 2 are at low risk and may be listed without delay, while those with a score of 6 or higher should be excluded from grafting. In addition, other factors have an established positive prognostic value, including cromophobe or clear cell papillary tumour, or G1 grade cancer, while medullary or Bellini's duct carcinoma or those with sarcomatoid dedifferentiation at histological examination should be excluded.Pending studies specifically focussing on cancer risk evaluation in people already treated for malignancy receiving long-term immunosuppressive therapy, all other patients had better be submitted to careful individual evaluation by an Oncologist and Urologist before being listed for renal transplantation.listing previous

show abstract

Renal cancer in kidney transplanted patients

Cited by 41 publications

References 79 publications

Honokiol inhibits c-Met-HO-1 tumor-promoting pathway and its cross-talk with calcineurin inhibitor-mediated renal cancer growth

Honokiol inhibits c-Met-HO-1 tumor-promoting pathway and its cross-talk with calcineurin inhibitor-mediated renal cancer growth

Urologic malignancies in kidney transplantation

Kidney transplantation in patients with previous renal cancer: a critical appraisal of current evidence and guidelines

Contact Info

Product

Resources

About