Renin angiotensin system deregulation as renal cancer risk factor (Review)

For numerous years, the non-cardiovascular role of the renin-angiotensin system (RAS) was underestimated, but recent studies have advanced the understanding of its function in various processes, including carcinogenesis. Numerous evidence comes from preclinical and clinical studies on the use of antihypertensive agents targeting the RAS, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers. It has been demonstrated that the use of ACEIs can alter the incidence of renal cell carcinoma (RCC) and may have a positive effect by prolonging patient survival. It has an effect on the complex action of ACEI, resulting in decreased angiotensin II (Ang-II) production and altered levels of bradykinin or Ang 1-7. The present review discusses the existing knowledge on the effects of ACE and its inhibitors on RCC cell lines, xenograft models, and patient survival in clinical studies. A brief introduction to molecular pathways aids in understanding the non-cardiovascular effects of RAS inhibitors and enables the conduction of studies on combined cancer treatment with the application of ACEIs. Recent evidence regarding the treatment of hypertension associated with tyrosine kinase inhibitors, one of the most pronounced and common side effects in modern RCC treatment, are also outlined. Captopril, an ACEI, may be used to lower blood pressure in patients, particularly due to its additional renoprotective actions

Culture in embryonic kidney serum and xeno-free media as renal cell carcinoma and renal cell carcinoma cancer stem cells research model

The use of fetal bovine serum hinders obtaining reproducible experimental results and should also be removed in hormone and growth factor studies. In particular hormones found in FBS act globally on cancer cell physiology and influence transcriptome and metabolome. The aim of our study was to develop a renal carcinoma serum free culture model optimized for (embryonal) renal cells in order to select the best study model for downstream auto-, para- or endocrine research. Secondary aim was to verify renal carcinoma stem cell culture for this application. In the study, we have cultured renal cell carcinoma primary tumour cell line (786-0) as well as human kidney cancer stem cells in standard 2D monolayer cultures in Roswell Park Memorial Institute Medium or Dulbecco’s Modified Eagle’s Medium and Complete Human Kidney Cancer Stem Cell Medium, respectively. Serum-free, animal-component free Human Embryonic Kidney 293 media were tested. Our results revealed that xeno-free embryonal renal cells optimized culture media provide a useful tool in RCC cancer biology research and at the same time enable effective growth of RCC. We propose bio-mimic RCC cell culture model with specific serum-free and xeno-free medium that promote RCC cell viability

32 Bezpośrednie wstrzykiwanie rTNFα do guzów nowotworowych wątroby

W około 70% badań sekcyjnych stwierdza się obecność guzów nowotworowych w wątrobie i są to głównie guzy przerzutowe. rTNFα jest cytokiną wykazującą cytotoksyczne działanie na komórki nowotworowe i jest stosowany w terapii eksperymentalnej nowotworów.W okresie od grudnia 1993 do stycznia 1995 r. rTNFα wstrzyknięto doguzowo z powodu zmian ogniskowych w wątrobie u 18 chorych (11 kobiet, 7 mężczyzn), badaniu klinicznemu zostali poddani chorzy z rozpoznaniami: pierwotny rak wątroby – 2 chorych, rak jelita grubego – 12 chorych, rak pęcherzyka żółciowego – 1 chorych, czerniak złośliwy – 1 chory, rak sutka – 1 chory, rak trzustki – 1 chory. rTNFα wstrzykiwano bezpośrednio do ognisk nowotworowych w wątrobie pod kontrolą ultrasonograficzną, w dawce od 100 do 500 μg (śr. 300 μg).U wszystkich chorych oceniano parametry kliniczne tj. temperaturę, czynność serca, ciśnienie tętnicze oraz laboratoryjne (biochemiczne i morfologiczne z krwi obwodowej). Dodatkowo u 6 chorych a rakiem jelita grubego, którzy otrzymywali 500μg rTNFα w surowicy oceniano kinetykę zmian stężenia rTNFα. Zmiany w obrębie ognisk nowotworowych oceniano w badaniu ultrasonograficznym.W badanej grupie chorych stwierdzono, że u 1 chorego z pierwotnym rakiem wątroby nie uzyskano zmiany obrazu ognisk patologicznych pod wpływem podawania rTNFα. U pozostałych 17 chorych stwierdzono zmiany w obrębie guzów obstrzykniętych tą cytokiną o charakterze hiperechogenicznym. W okresie od kilku do 72 godzin od chwili wstrzyknięcia stwierdzono normalizację parametrów klinicznych, biochemicznych i morfologicznych krwi. Największe stężenie rTNFα w surowicy krwi obwodowej stwierdzono w 1 godzinę od chwili wstrzyknięcia rTNFα −133,96 +/−291,40 pg/ml (ta wartość przed leczeniem wynosiła 279,72+/−23,20 pg/ml). Czas przeżycia chorych od chwili doguzowego wstrzyknięcia rTNFα wynosił od4 do 43 tygodni (mediana 18,8 tygodni)

Development of extracellular matrix supported 3D culture of renal cancer cells and renal cancer stem cells

Novel experimental conditions of cancer cell line culture have evolved throughout the recent years, with significantly growing interest in xeno-free, serum-free and three-dimensional culture variants. The choice of proper culture media may enable to mimic tumor microenvironment and promotion of cancer stem cells proliferation. To assess whether stem-like phenotype inducing media may be applied in renal cancer stem cell research, we performed a widespread screening of 13 cell culture media dedicated for mesenchymal cells, stem cells as well as mesenchymal stem cells. We have also screened extracellular matrix compounds and selected optimal RCC 3D—ECM supported culture model. Our results revealed that 786-O as well as HKCSCs cell line cultures in xeno-free media (NutriStem/StemXvivo) and laminin coated plates provide a useful tool in RCC cancer biology research and at the same time enable effective drug toxicity screening. We propose bio-mimic 3D RCC cell culture model with specific low-serum and xeno-free media that promote RCC cell viability and stem-like phenotype according to the tested genes encoding stemness factors including E-cadherin, N-cadherin, HIF1, HIF2, VEGF, SOX2, PAX2 and NESTIN

Second-line cabozantinib versus nivolumab in advanced renal cell carcinoma: Systematic review and indirect treatment comparison

Background: Nivolumab and cabozantinib, two new treatment options for previously-treated advanced/metastatic renal cell carcinoma (aRCC), have recently been approved. Methods: Two independent reviewers performed study selection, data extraction, and risk of bias assessment. Indirect treatment comparisons were carried out by directly assessing HR differences and statistical modeling of Kaplan-Meier curves from these two trials. Results: Publications identified showed that no head-to-head comparisons had been carried out. Two indirect treatment comparisons used agreed that there was no significant difference in OS between cabozantinib and nivolumab and that cabozantinib significantly improved PFS compared to nivolumab. Conclusions: The field of aRCC treatments is evolving rapidly, creating opportunities for individualized treatments and challenges for clinicians to keep up with the evidence. In lieu of availability of direct comparisons of all options, advanced modeling results presented herein can help to inform and improve personalized treatments

Opening an onconephrology clinic: recommendations and basic requirements

Onconephrology is a rapidly evolving subspeciality that covers all areas of renal involvement in cancer patients. The complexity of the field may benefit from well-defined multidisciplinary management administered by a dedicated team. Since there is an increasing need to address the needs of this population in dedicated outpatient clinics, it is critical to highlight basic characteristics and to suggest areas of development. In this brief perspective article, we analyse the requirements of an onconephrology clinic in terms of logistics, critical mass of patients and building a multidisciplinary team. We will further discuss which patients to refer and which conditions to treat. The last part of the article is dedicated to education and performance indicators and to analysis of the potential advantages of applying the hub-and-spoke model to this field. The ultimate aim of this experience-based article is to initiate debate about what an onconephrology outpatient clinic might look like in order to ensure the highest quality of care for this growing population of patients

Opening an onconephrology clinic: Recommendations and basic requirements

Onconephrology is a rapidly evolving subspeciality that covers all areas of renal involvement in cancer patients. The complexity of the field may benefit from well-defined multidisciplinary management administered by a dedicated team. Since there is an increasing need to address the needs of this population in dedicated outpatient clinics, it is critical to highlight basic characteristics and to suggest areas of development. In this brief perspective article, we analyse the requirements of an onconephrology clinic in terms of logistics, critical mass of patients and building a multidisciplinary team. We will further discuss which patients to refer and which conditions to treat. The last part of the article is dedicated to education and performance indicators and to analysis of the potential advantages of applying the hub-and-spoke model to this field. The ultimate aim of this experience-based article is to initiate debate about what an onconephrology outpatient clinic might look like in order to ensure the highest quality of care for this growing population of patients

Metastatic renal cell cancer treatments: An indirect comparison meta-analysis

Abstract Background Treatment for metastatic renal cell cancer (mRCC) has advanced dramatically with understanding of the pathogenesis of the disease. New treatment options may provide improved progression-free survival (PFS). We aimed to determine the relative effectiveness of new therapies in this field. Methods We conducted comprehensive searches of 11 electronic databases from inception to April 2008. We included randomized trials (RCTs) that evaluated bevacizumab, sorafenib, and sunitinib. Two reviewers independently extracted data, in duplicate. Our primary outcome was investigator-assessed PFS. We performed random-effects meta-analysis with a mixed treatment comparison analysis. Results We included 3 bevacizumab (2 of bevacizumab plus interferon-a [IFN-a]), 2 sorafenib, 1 sunitinib, and 1 temsirolimus trials (total n = 3,957). All interventions offer advantages for PFS. Using indirect comparisons with interferon-α as the common comparator, we found that sunitinib was superior to both sorafenib (HR 0.58, 95% CI, 0.38–0.86, P = < 0.001) and bevacizumab + IFN-a (HR 0.75, 95% CI, 0.60–0.93, P = 0.001). Sorafenib was not statistically different from bevacizumab +IFN-a in this same indirect comparison analysis (HR 0.77, 95% CI, 0.52–1.13, P = 0.23). Using placebo as the similar comparator, we were unable to display a significant difference between sorafenib and bevacizumab alone (HR 0.81, 95% CI, 0.58–1.12, P = 0.23). Temsirolimus provided significant PFS in patients with poor prognosis (HR 0.69, 95% CI, 0.57–0.85). Conclusion New interventions for mRCC offer a favourable PFS for mRCC compared to interferon-α and placebo