Comprehensive Analysis and Identification of an Immune-Related Gene Signature with Prognostic Value for Prostate Cancer.

BACKGROUND: The tumor microenvironment (TME) has recently been proven to play a crucial role in the development and prognosis of tumors. However, the current knowledge on the potential of the TME in prostate cancer (PCa) remains scarce. PURPOSE: This study aims to elucidate the value of TME-related genes for PCa prognosis by integrative bioinformatics analysis. MATERIALS AND METHODS: We downloaded the immune and stromal scores of PCa samples via the ESTIMATE and correlated these scores to clinicopathological characteristics and recurrence-free survival (RFS) of patients. Based on these scores, the TME-related differentially expressed genes were identified for functional enrichment analysis. Cox regression analyses were performed to identify prognostic genes and establish a predictive risk model. Moreover, gene set enrichment analysis (GSEA) was performed to evaluate the relationship between risk score and immune pathway. RESULTS: The stromal and immune scores were associated with clinicopathological characteristics and RFS in PCa patients. In total, 238 intersecting differentially expressed genes were identified. Functional enrichment analysis further revealed that these genes dramatically participated in the immune-related pathways. The immune-related risk model was built with C-type lectin domain containing 7A (CLEC7A) and collagen type XI alpha 1 chain (COL11A1) using Cox regression analyses. Kaplan-Meier survival analysis showed that the expression levels of CLEC7A and COL11A1 were significantly associated with the RFS. Further, the RFS time in high-risk group was significantly shorter than that in low-risk group. The areas under the curve for the risk model in predicting 3- and 5-year RFS rates were 0.694 and 0.731, respectively. GSEA suggested that immunosuppression existed in high-risk PCa patients. CONCLUSION: CLEC7A and COL11A1 were selected to build a predictive risk model, which may help clinicians to assess the prognosis of PCa patients and select appropriate targets for immunotherapy.

Safety and Efficacy of Right Retroperitoneal Laparoscopic Live Donor Nephrectomy: A Retrospective Single-Center Study.

BACKGROUND The aim of this study was to investigate the efficacy and safety of right retroperitoneal laparoscopic live donor nephrectomy (LDN) in 81 cases of living-related renal transplant. MATERIAL AND METHODS We retrospectively reviewed all living-related donors who underwent right retroperitoneoscopic living donor nephrectomy between June 2010 and December 2017 at the First Hospital of Jilin University and their corresponding recipients. Demographic and clinical data were collected from the hospital's electronic clinical data system. Data on preoperative renal retention parameters, operative time, and donor kidney warm ischemia time, the trimmed length of the renal artery and vein of donor kidney, and the time to extubation were recorded. Complications in both donors and recipients were recorded. RESULTS We included 81 donors who underwent successful right-sided retroperitoneoscopic LDN, with 31 males and 50 females and a mean age of 47.1 years (range 21-63 years). There was no intraoperative conversion to open donor nephrectomy. The mean operative time was 120.68±29.8 min. The mean warm ischemic time was 49.26±3.86 s. The estimate blood loss was 54.32 mL (range 50-400 mL). The median length of hospital stay was 7 days (range 4-13 days). There was neither intraoperative complication such as hemorrhage or lymph fistula nor kidney graft injury. There was no graft renal vein thrombosis and ureteral stricture or other complications. No graft rejection occurred. CONCLUSIONS Right retroperitoneal laparoscopic live donor nephrectomy is safe and effective for renal transplant in living-related renal transplant by laparoscopic excision and extraction of the right kidney with vena cava flap.

Clopidogrel Reduces Fibronectin Accumulation and Improves Diabetes-Induced Renal Fibrosis.

Hyperglycemia-induced renal fibrosis causes end-stage renal disease. Clopidogrel, a platelet inhibitor, is often administered to decrease cardiovascular events in diabetic patients. We investigated whether clopidogrel can reduce diabetes-induced renal fibrosis in a streptozotocin-induced type 1 diabetes murine model and fibronectin involvement in this protective response. Diabetic and age-matched controls were sacrificed three months after the onset of diabetes, and additional controls and diabetic animals were further treated with clopidogrel or vehicle for three months. Diabetes induced renal morphological changes and fibrosis after three months. Clopidogrel, administered during the last three months, significantly decreased blood glucose, collagen and fibronectin expression compared to vehicle-treated diabetic mice. Diabetes increased TGF-ß expression, inducing fibrosis via Smad-independent pathways, MAP kinases, and Akt activation at three months but returned to baseline at six months, whereas the expression of fibronectin and collagen remained elevated. Our results suggest that activation of TGF-ß, CTGF, and MAP kinases are early profibrotic signaling events, resulting in significant fibronectin accumulation at the early time point and returning to baseline at a later time point. Akt activation at the three-month time point may serve as an adaptive response in T1D. Mechanisms of clopidogrel therapeutic effect on the diabetic kidney remain to be investigated as this clinically approved compound could provide novel approaches to prevent diabetes-induced renal disease, therefore improving patients' survival.

Cell-penetrating Peptide-coated Liposomes for Drug Delivery Across the Blood-Brain Barrier.

BACKGROUND/AIM: Glioma is a deadly form of brain cancer. Doxorubicin is cytotoxic against glioma cells. However, the blood-brain barrier (BBB) limits its ability to be delivered to the brain. MATERIALS AND METHODS: Liposomes (R8PLP) formed from, 1,2-dioleoyl-3-trimethylammonium-propane chloride (DOTAP), 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[methoxy-(polyethylene glycol)-2000] (PEG-DSPE), cholesterol and egg phosphatidylcholine (ePC) were modified by cell-penetrating peptide R8 conjugated with oleic acid as a novel method for delivering doxorubicin. The antitumor effect of R8PLP was evaluated by uptake, cytotoxicity and brain accumulation. RESULTS: The size of R8PLP was 95 nm. Doxorubicin was loaded into R8PLP by active loading with more than 95% encapsulation efficiency. Cellular uptake of R8PLP by U87-MG cells was 8.6-fold higher than that of unmodified liposomes. R8PLP reduced cell viability by 16.18% and 18.11% compared to cholesterol-ePC-liposomes and free doxorubicin, respectively, at 3.6 µM after 24 h treatment. The biodistribution of doxorubicin in the brain was significantly improved by R8PLP. The area under the concentration-time curve (AUC0.5-12 h) of R8PLP was 2.4-times higher than that of cholesterol-ePC-PEG-DSPE-liposomes. CONCLUSION: These results suggest that R8-conjugated oleic acid-modified liposomes are effective delivery vehicles for glioma.

Anticancer Properties of Fenofibrate: A Repurposing Use.

Cancer is a leading cause of death throughout the world, and cancer therapy remains a big medical challenge in terms of both its therapeutic efficacy and safety. Therefore, to find out a safe anticancer drug has been long goal for oncologist and medical scientists. Among clinically used medicines with no or little toxicity, fenofibrate is a drug of the fibrate class that plays an important role in lowering the levels of serum cholesterol and triglycerides while elevating the levels of high-density lipoproteins. Recently, several studies have implied that fenofibrate may exert anticancer effects via a variety of pathways involved in apoptosis, cell-cycle arrest, invasion, and migration. Given the great potential that fenofibrate may have anticancer effects, this review was to investigate all published works which directly or indirectly support the anticancer activity of fenofibrate. These studies provide evidence that fenofibrate exerted antitumor effects in several human cancer cell lines, such as breast, liver, glioma, prostate, pancreas, and lung cancer cell lines. Among these studies some have further confirmed the possibility and efficacy of fenofibrate anticancer in xenograft mouse models. In the last part of this review, we also discuss the potential mechanisms of action of fenofibrate based on the available information. Overall, we may repurpose fenofibrate as an anticancer drug in cancer treatment, which urgently need further and comprehensively investigated.

Circulating vitamin D concentration and risk of prostate cancer: a dose-response meta-analysis of prospective studies.

BACKGROUND: Though many studies have been performed to elucidate the association between circulating vitamin D and prostate cancer, no conclusive result is available. We carried out a dose-response meta-analysis to quantitatively examine the association of circulating 25-hydroxyvitamin D (25[OH]D) concentration with prostate cancer. METHODS: Only prospective studies examining the associations of circulating 25[OH]D concentration with prostate cancer were eligible for the meta-analysis. A random-effect meta-analysis was done first, to calculate the summary relative risk (RR) and 95% confidence intervals (CIs) comparing the higher concentration with the lower concentration of 25[OH]D. A dose-response meta-analysis using random-effects model was then carried out to evaluate the nonlinearity and calculate the summary RR caused per 10 ng/mL increment. RESULTS: Nineteen prospective cohort or nested case-control studies were included. Higher 25[OH]D concentration was significantly correlated with elevated risk of prostate cancer (RR =1.15, 95% CI 1.06-1.24). No nonlinear relationship was found between 25[OH]D concentration and risk of prostate cancer (P=0.654). Dose-response meta-analysis showed that the summary RR caused per 10 ng/mL increment in circulating 25[OH]D concentration was 1.04 (95% CI 1.02-1.06). Subgroup analysis also found a modest dose-response relationship. Funnel plot and Egger's test did not detect publication bias. CONCLUSION: The findings suggest that highest 25[OH]D concentration is correlated with elevated risk of prostate cancer and a modest dose-response effect exists in this association; however, more studies are needed.

The beneficial effects of Zn on Akt-mediated insulin and cell survival signaling pathways in diabetes.

Zinc is one of the essential trace elements and participates in numerous physiological processes. Abnormalities in zinc homeostasis often result in the pathogenesis of various chronic metabolic disorders, such as diabetes and its complications. Zinc has insulin-mimetic and anti-diabetic effects and deficiency has been shown to aggravate diabetes-induced oxidative stress and tissue injury in diabetic rodent models and human subjects with diabetes. Akt signaling pathway plays a central role in insulin-stimulated glucose metabolism and cell survival. Anti-diabetic effects of zinc are largely dependent on the activation of Akt signaling. Zn is also an inducer of metallothionein that plays important role in anti-oxidative stress and damage. However, the exact molecular mechanisms underlying zinc-induced activation of Akt signaling pathway remains to be elucidated. This review summarizes the recent advances in deciphering the possible mechanisms of zinc on Akt-mediated insulin and cell survival signaling pathways in diabetes conditions. Insights into the effects of zinc on epigenetic regulation and autophagy in diabetic nephropathy are also discussed in the latter part of this review.

Lower pole approach in retroperitoneal laparoscopic radical nephrectomy: a new approach for the management of renal vascular pedicle.

BACKGROUND: The objective of this study was to examine the effectiveness and safety of lower pole (LP) approach in retroperitoneal laparoscopic radical nephrectomy (LRN). METHODS: One hundred thirty-two renal cancer patients were scheduled for selective retroperitoneal LRN. The surgery parameters and outcomes were compared. Out of 132 patients, 78 (59.1%) patients underwent LRN via LP approach, while 54 (40.9%) patients underwent LRN via lateroposterior space (LPS) approach. RESULTS: Compared to LPS group, the LP group had a higher body mass index (27.0 ± 1.7 kg/m2 vs. 24.5 ± 1.8 kg/m2, P <  0.0001) and a larger tumor size (6.9 ± 3.5 cm vs. 4.1 ± 3.3 cm, P <  0.0001). The LP approach reduced the volumes of blood loss and transfusion significantly (135.3 ± 17.2 mL vs. 219.6 ± 30.9 mL, P <  0.0001; 55.6 ± 28.3 vs. 141.1 ± 50.4 mL, P <  0.0001) as compared to the LPS approach. The LP approach also decreased the risk of conversion to open procedure (1.3 vs. 7.4%, P <  0.05). CONCLUSIONS: The LP approach is an effective and safe alternative to the LPS approach for retroperitoneal LRN and might be more suitable for patients with obesity, large tumors, tumors located at the medial part of the kidney, or renal pedicular adhesion.

Fenofibrate inhibits mTOR-p70S6K signaling and simultaneously induces cell death in human prostate cancer cells.

Fenofibrate is the most widely used lipid-lowering drug, but it seems to have anti-tumor effects in several tumor cell lines. However, there are only a few reports on its effects on human prostate cancer cells. Thus, we investigated the anti-proliferative effects of fenofibrate on human prostate cancer cells and potential mechanisms. The methods used include cell viability analysis with an MTT assay, as well as apoptosis and related signaling pathway analyses with flow cytometry and Western blotting. Fenofibrate inhibited PC-3 cell growth in dose- and time-dependent manners. The fenofibrate-induced cell death is predominantly apoptotic death that is mediated by both the caspase-3 activation and apoptosis-inducing factor (AIF) signaling pathways. Fenofibrate also increased the expression of Bad and decreased the expression of Bcl-2 and Survivin. Mechanistically, fenofibrate-induced cell death was associated with decreased p-p70S6K and the mammalian target of rapamycin (mTOR) phosphorylation levels. When further exploring the upstream mediators of mTOR/p70S6K, we found that fenofibrate increased p38 MAPK and AMPK phosphorylation but did not significantly change the phosphorylation levels of PI3K, AKT, and JNK. However, the inhibition of either p38 MAPK or AMPK with their specific inhibitor did not change the effect of fenofibrate-induced cell death. These findings suggested that fenofibrate indeed significantly inhibited the proliferation of PC-3 cells via apoptotic action, which is associated with the inactivation of the mTOR/p70S6K-dependent cell survival pathway. Although the mechanisms by which fenofibrate inactivates this pathway remains unclear, this study reveals great potential for its use for the clinical treatment of prostate cancers.

Dynamics of B Cell Recovery In Kidney/Bone Marrow Transplant Recipients.

BACKGROUND: Previous studies identified B cell gene signatures and predominance of specific B cell subsets as a marker of operational tolerance after kidney transplantation. These findings suggested a role for B cells in the establishment or maintenance of tolerance. Here we analyzed B cell recovery in 4 subjects, 3 of whom achieved tolerance after combined kidney/bone marrow transplantation. METHODS: Peripheral B cell subsets were examined longitudinally by flow cytometry. Immunoglobulin heavy chain repertoire analysis was performed using next-generation sequencing. Lastly, the patients' serum reactivity to HLA was assessed by Luminex. RESULTS: B cell counts recovered approximately 1 year posttransplant except for 1 subject who experienced delayed reconstitution. This subject resumed immunosuppression for acute rejection at 10 months posttransplant and underwent preemptive retransplantation at 3 years for chronic rejection. B cell recovery was accompanied by a high frequency of CD20 + CD24CD38 transitional B cells and a diversified clonal repertoire. However, all 4 subjects showed prevalence of CD20 + CD27+ memory B cells around 6 months posttransplant when B cell counts were still low and the clonal B cell repertoire very limited. The predominance of memory B cells was also associated with high levels of somatically mutated immunoglobulin heavy chain variable sequences and transient serum reactivity to HLA. CONCLUSIONS: Our observations reveal the presence of memory B cells early posttransplant that likely escaped the preparative regimen at a time consistent with the establishment of tolerance. Further studies are warranted to characterize the functional properties of these persisting memory cells and evaluate their potential contribution to tolerance induction.

Farnesoid X receptor ligand CDCA suppresses human prostate cancer cells growth by inhibiting lipid metabolism via targeting sterol response element binding protein 1.

AIM: A wealth of studies have demonstrated that abnormal cellular lipid metabolism plays an important role in prostate cancer (PCa) development. Therefore, manipulating lipid metabolism is a potential PCa therapy strategy. In this study, our goal is to investigate the role of farnesoid X receptor (FXR) in regulating the proliferation and lipid metabolism of human PCa cells following its ligand chenodexycholic acid (CDCA) treatment. METHODS: Oil Red O was used to stain lipid contents in PCa cells, and siRNA knockdown was performed to deplete FXR expression. To study the cell proliferation when treated by CDCA or FXR knockdown, cell counting kit 8 (CCK8) was adopted to evaluate tumor cell growth. Western blot was used for protein analysis. RESULTS: Our data suggest that activation of FXR by CDCA reduces lipid accumulation and significantly inhibits cells proliferation in prostate tumor cells. Instead, CDCA treatment doesn't affect normal prostate epithelial RWPE-1 cells growth in vitro. FXR activation decreases mRNA and protein levels of sterol regulatory element binding protein 1 (SREBP1) and some other key regulators involved in lipid metabolism. Depletion of FXR by siRNA attenuates the inhibitory effects. CONCLUSION: Our study indicates that activation of FXR inhibits lipid metabolism via SREBP1 pathway and further suppresses prostate tumor growth in vitro.

Effect of preoperative intravenous oxycodone administration on sufentanil consumption after retroperitoneal laparoscopic nephrectomy.

BACKGROUND: The aim of this study was to evaluate the efficacy of preoperative intravenous oxycodone administration on postoperative sufentanil consumption in patients undergoing retroperitoneal laparoscopic nephrectomy. METHODS: Fifty patients scheduled for retroperitoneal laparoscopic nephrectomy were enrolled and randomly assigned to two groups- patients in Group O (n = 25) received intravenously 0.1 mg kg⁻¹ oxycodone; while the patients in Group C (n = 25) received 0.1 mL kg⁻¹ normal saline for 2 min, 10 min before the operation. All of the participants received intravenous sufentanil patient-controlled analgesia (PCA) after extubation, using a PCA device. The sufentanil consumption, rescue analgesia, Ramsay sedation scale (RSS) and visual analogue scale (VAS) scores at rest and during cough, the overall satisfaction and undesired events were all assessed. RESULTS: Cumulative sufentanil consumption delivered by PCA was significantly lower in Group O at all time points. VAS scores at rest and during coughing at 1, 2, 4, 8 and 12 hours after extubation of the patient were significantly lower in Group O than in Group C. There were no significant differences between the two groups according to the number of patients administered tramadol, RSS and the incidence of side effects. The degree of patients' satisfaction was higher in Group O. CONCLUSION: Preoperative intravenous oxycodone can reduce postoperative cumulative sufentanil consumption and postoperative pain intensity without an increase in side effects.

Advantages of caudal block over intrarectal local anesthesia plus periprostatic nerve block for transrectal ultrasound guided prostate biopsy.

OBJECTIVE: To compare caudal block with intrarectal local anesthesia plus periprostatic nerve block for transrectal ultrasound guided prostate biopsy. METHODS: One hundred and ninety patients scheduled for transrectal ultrasound guided prostate biopsy were randomized equally into Group-A who received caudal block (20 ml 1.2% lidocaine) and Group-B who received intrarectal local anesthesia (0.3% oxybuprocaine cream) plus periprostatic nerve block (10 ml 1% lidocaine plus 0.5% ropivacaine) before biopsy. During and after the procedure, the patients rated the level of pain/discomfort at various time points. Complications during the whole study period and the patient overall satisfaction were also evaluated. RESULTS: More pain and discomfort was detected during periprostatic nerve block than during caudal block. Pain and discomfort was significantly lower during prostate biopsy and during the manipulation of the probe in the rectum in Group-A than in Group-B. No significant differences were detected in the pain intensity after biopsy and side effects between the two groups. CONCLUSIONS: Caudal block provides better anesthesia than periprostatic nerve block plus intrarectal local anesthesia for TRUS guided prostate biopsy without an increase of side effects.

Effect of preoperative intravenous oxycodone on sufentanil consumption after laparoscopic radical gastrectomy.

OBJECTIVE: To investigate the effect of preoperative intravenous oxycodone on sufentanil consumption by patient-controlled intravenous analgesia (PCIA) after laparoscopic radical gastrectomy. METHODOLOGY: Forty-six patients scheduled for laparoscopic radical gastrectomy were randomly divided into two groups: group O (n = 23) received intravenous oxycodone (0.1 mg/kg) 10 minutes before surgery over 2 minutes and group C (n = 23) received normal saline as a placebo. A standardized general anesthesia and intravenous sufentanil PCIA were applied to all patients. Postoperative sufentanil doses delivered by PCIA, rescue analgesia, Ramsay sedation scale, visual analog scale (VAS) scores at rest, the overall satisfaction, and side effects were assessed. RESULTS: The numbers of sufentanil doses delivered by PCIA were significantly fewer and VAS scores at rest were significantly lower in group O than in group C at various time points after operation. The overall satisfaction degree was higher in group O than in group C. The incidences of side effects were similar between the two groups. CONCLUSIONS: Preoperative intravenous oxycodone can reduce postoperative pain and sufentanil consumption after laparoscopic radical gastrectomy without an increase of side effects.

Evidence to Support a Contribution of Polyreactive Antibodies to HLA Serum Reactivity.

BACKGROUND: Assessing the serum reactivity to HLA is essential for the evaluation of transplant candidates and the follow-up of allograft recipients. In this study, we look for evidence at the clonal level that polyreactive antibodies cross-reactive to apoptotic cells and multiple autoantigens can also react to HLA and contribute to the overall serum reactivity. METHODS: We immortalized B cell clones from the blood of 2 kidney transplant recipients and characterized their reactivity to self-antigens, apoptotic cells as well as native, denatured, and cryptic HLA determinants using enzyme-linked immunosorbent assay (ELISA), immunofluorescence, flow cytometry and Luminex assays. We also assessed the reactivity of 300 pretransplant serum specimens to HLA and apoptotic cells. RESULTS: We report here 4 distinct B cell clones cross-reactive to self and HLA class I. All 4 clones reacted to numerous HLA class I alleles but did not appear to target canonical "shared" epitopes. In parallel experiments, we observed a strong correlation between IgG reactivity to HLA and apoptotic cells in pretransplant serum samples collected from 300 kidney transplant recipients. Further analysis revealed that samples with higher reactivity to apoptotic cells displayed significantly higher class I percent panel-reactive antibodies compared to samples with low reactivity to apoptotic cells. CONCLUSIONS: We provide here (1) proof of principle at the clonal level that human polyreactive antibodies can cross-react to HLA, multiple self-antigens and apoptotic cells and (2) supportive evidence that polyreactive antibodies contribute to overall HLA reactivity in the serum of patients awaiting kidney transplant.

CLINICAL RESEARCH REGARDING PREEMPTIVE ANALGESIC EFFECT OF PREOPERATIVE KETAMINE AFTER TRANSURETHRAL RESECTION OF PROSTATE.

OBJECTIVE: To investigate whether a single intravenous dose of ketamine before transurethral resection of prostate (TURP) led to reduced postoperative pain and tramadol consumption. METHODOLOGY: Sixty patients undergoing elective TURP were randomized into one of two groups: the ketamine group (Group K, n = 30) received intravenous 0.5 mg/kg ketamine 10 min before surgery, and the control group (Group C, n = 30) received an equivalent volume of normal saline 30 min before surgery. A standardized general anesthesia method was used with a laryngeal mask airway device in all patients. Data on pain intensity, incidence of lower urinary tract discomfort, time to the first analgesic requirement, tramadol analgesia and consumption, overall patient satisfaction and side effects were recorded for 24 h after extubation of the patients. RESULTS: Group K had significantly decreased postoperative pain scores at 1, 2, 6, and 12 h. The number of patients who required postoperative analgesia was fewer and postoperative tramadol consumption was significantly less in Group K as compared with Group C. There was no significant difference in the incidence of lower urinary tract discomfort or any of side effects. The patients in Group K were more satisfied. CONCLUSION: Preemptive 0.5 mg/kg ketamine has a definitive role of preemptive analgesia for TURP without influence of LUT discomfort or an increase of adverse effects.

A case of kidney transplantation using donation after circulatory death with renal calculi.

Donation after circulatory death (DCD) supplies a big percentage of the organ source pool. Compared to living-related donations, donor kidneys from DCD are commonly with lower quality since they inevitably suffer from hypoxia, hypotension, and inadequate organ perfusion during the progression to circulatory arrest. The current case presents a 44-year-old male donor with wide range subarachnoid hemorrhage and multiple skull fracture from a car accident. Multiple stones were detected in his right kidney. We performed a modified ex vivo pyelolithotomy and ureteroscopy on the bench to render a stone-free allograft. We also improved the donor kidney with hypothermic/perfusion preservation machine before renal transplantation. The recipient showed no complications during the first two-month post-operational follow-up. Such a donor kidney with stones may probably be discarded by conventional perspective. Yet, the combination of the ex vivo bench-surgery technique and hypothermic oxygenation/perfusion makes it a qualified donor kidney. Thus we have demonstrated a promising way of saving borderline qualified DCD donor kidneys.

Ischemia/reperfusion-induced CHOP expression promotes apoptosis and impairs renal function recovery: the role of acidosis and GPR4.

Endoplasmic reticulum (ER) stress-induced apoptosis is implicated in a wide range of diseases, including ischemia/reperfusion injury (IRI). As a common feature of ER stress, the role of CCAT/enhancer-binding protein homologous protein (CHOP) in renal IRI has not been thoroughly investigated. We found that IR led to renal CHOP expression, accompanied by apoptosis induction. Renal IRI was markedly alleviated in CHOP-/- mice. Observations from bone marrow chimeras showed that this was based on CHOP inactivation in renal parenchymal cells rather than inflammatory cells. In vivo and in vitro studies demonstrated that IRI induced CHOP expression in both endothelial and epithelial cells, which was responsible for apoptosis induction. These results were reinforced by the observation that CHOP knockout led to improvement of the postischemic microcirculatory recovery. In vitro studies revealed hypoxia-induced acidosis to be a major inducer of CHOP in endothelial cells, and neutralizing acidosis not only diminished CHOP protein, but also reduced apoptosis. Finally, knockdown of a proton-sensing G protein-coupled receptor GPR4 markedly reduced CHOP expression and endothelial cell apoptosis after hypoxia exposure. These results highlight the importance of hypoxia-acidosis in ER stress signaling regulation in ischemic kidneys and suggest that GPR4 inhibitors or agents targeting CHOP expression may be promising in the treatment of renal IRI.

Renal solitary fibrous tumour: A rare pathological entity.

A solitary fibrous tumour (SFT) is a rare mesenchymal cell neoplasm that can develop at any site. SFT of the kidney is extremely rare. Recently, we had a case of solitary fibrous tumour involving the left kidney in a 71-year-old female patient. The SFT was incidentally found by imaging modalities at the time of a physical workup. Computed tomography and retrograde pyelography showed a 4 × 3.5 × 4-cm nodular mass in the middle poles of the left kidney adjacent to the renal pelvis. A laparoscopic radical resection of the left kidney was performed. The tumour was well-circumscribed and composed of a mixture of spindle cells; microscopically, we found dense collagenous bands. Immunohistochemical studies showed strong reactions with CD34, bcl-2 and CD99. A nuclear positivity with Ki-67 was observed in less than 1% of cells. The tumour was negative for desmin, SMA and CD117. Histopathological and immunohistochemical studies confirmed the diagnosis of a solitary fibrous tumour.

Multilocular cystic nephroma treated with laparoscopic nephron-sparing surgery: A case report.

Multilocular cystic nephroma is a relatively rare benign tumour of the kidney, which usually presents as a unilateral multicystic renal mass without solid elements. The lesions typically have a bimodal age, with peak incidence in male children under 24 months and another one in women over 40 old. We present an unusual case report of multilocular cystic nephroma in the right kidney in a 30-year-old male. Laparoscopic partial nephrectomy was performed. The pathologic examination confirmed a multi-locular cystic nephroma in the right renal specimens. We present the image findings, pathological features, treatment alternatives and a review of the literature.