Urinary Excretion of Cyanuric Acid in Association with Urolithiasis: A Matched Case-Control Study in Shanghai Adults

Melamine (MEL) has raised human concern since the 2008 milk scandal. Co-exposure to MEL and one of its analogues, cyanuric acid (CYA), has been reported to have a synergistic effect on promoting urolithiasis. However, few epidemiological studies have reported urolithiasis in association with exposure to CYA based on our knowledge. We therefore conducted a case-control study to investigate whether cases of urolithiasis had higher excretion of urinary CYA than the controls. Spot urine samples from 70 adult cases and first-morning urine samples from 70 controls (matched by age and sex) were collected for the measurement of MEL, CYA, and other two analogues in urine. The case group also had 2.81-fold higher concentration of urinary CYA than the control group (34.87 versus 12.43 ng/mL, p-value < 0.001). Multivariate conditional logistic regression models adjusting potential confounders of personal characteristics identified the risk factor of urinary CYA as a continuous variable with odds ratio (OR) (95% confidence interval, 95%CI) of 1.11 (1.02–1.21) (p-value = 0.021) and having meals at restaurants with OR of 5.71 (1.01–32.31) (p-value = 0.049). Compared to the participants having the lowest quartile of CYA concentration in urine, participants at the second, third, and fourth quartile groups had ORs of 13.94, 83.69, and 118.65 with p-values of 0.004, <0.001, and <0.001, respectively. The high excretion of urinary CYA in urolithiasis cases might be the sign of stones in patients consisting of CYA, then proving the attribution of CYA exposure in the etiology of urolithiasis. These findings are important since CYA is a degraded by-product of chlorinated isocyanuric acid disinfectants, which are widely used in daily life not only in swimming pool water but also in other scenarios, such as serving as anti-pandemic disinfectants. Risk assessment of CYA serving as a by-product of disinfectants needs to be conducted in future studies

Mini-flank supra-12th rib incision for open partial nephrectomy compared with laparoscopic partial nephrectomy and traditional open partial nephrectomy.

PURPOSE: The purpose of this study was to report our approach of partial nephrectomy (PN) using a supra-12th rib mini-flank incision. We compared mini-incision open partial nephrectomy (MI-OPN) with open partial nephrectomy (OPN) and laparoscopic partial nephrectomy (LPN) to verify whether MI-OPN can be an alternative to OPN and LPN. METHODS: This was a retrospective single-center study including 194 patients who underwent partial nephrectomy (PN) between February 2005 and December 2010. Demographic, perioperative, and complication data were compared among the MI-OPN group, OPN group and LPN group. RESULTS: No statistical differences were reported in either group for age, sex, BMI, tumour side (right or left kidney), RENAL nephrometry scores, PADUA score and preoperative eGFR. The operative time was longer in LPN group when compared with MI-OPN and OPN group (all P<0.001). The warm ischemia time of LPN group was longer than MI-OPN group (P = 0.032) and OPN group (P = 0.005). The length of stay of LPN group was shorter than OPN group (P = 0.018), but was similar to MI-OPN group (P = 0.094). The incidence of renal artery clamping was lower in OPN group when compared with MI-OPN and LPN group (all P<0.001). More estimated blood loss was found in OPN group when compared with MI-OPN group (p = 0.003) and LPN group (P = 0.014). The overall incidence of postoperative complications was similar. CONCLUSIONS: The approach of MI-OPN can couple the benefits of both minimally invasive and open partial nephrectomy techniques with less estimated blood loss, shorter operative time, shorter length of stay, less postoperative complications, and a smaller incision. MI-OPN may be an effective alternative to laparoscopic or traditional open approaches, which maybe more suitable for the tumors with high RENAL nephrometry score or PADUA score

HSP90 Inhibitor Encapsulated Photo-Theranostic Nanoparticles for Synergistic Combination Cancer Therapy.

Photodynamic therapy (PDT) is a promising non-invasive therapeutic modality that has been proposed for treating prostate cancer, but the procedure is associated with limited efficacy, tumor recurrence and photo-toxicity. In the present study, we proposed to develop a novel multifunctional nano-platform for targeted delivery of heat, reactive oxygen species (ROS) and heat shock protein 90 (Hsp90) inhibitor simultaneously for combination therapy against prostate cancer. This new nano-platform combines two newly developed entities: 1) a unique organic and biocompatible nanoporphyrin-based drug delivery system that can generate efficient heat and ROS simultaneously with light activation at the tumor sites for dual-modal photothermal- and photodynamic- therapy (PTT/PDT), and 2) new nano-formulations of Hsp90 inhibitors that can decrease the levels of pro-survival and angiogenic signaling molecules induced by phototherapy, therefore, further sensitizing cancer cells to phototherapy. Furthermore, the nanoparticles have activatable near infrared (NIR) fluorescence for optical imaging to conveniently monitor the real-time drug delivery in both subcutaneous and orthotopic mouse models bearing prostate cancer xenograft. This novel multifunctional nano-platform has great potential to improve the care of prostate cancer patients through targeted combination therapy

Comparisons of the receiver operating characteristic (ROC) curves for prediction of survival by the EZH2 score, TNM stage, and H3K27me3 score.

<p>(A) (E) DFS, (B) (F) OS in the training set. (C) (G) DFS, (D) (H) OS in the validation set. (A-D) the area under the ROC curves (AUROC) of EZH2 score versus the AUROC of TNM stage, or H3K27me3 score. (E-H) the AUROC of the combined EZH2 and TNM stage model versus the AUROC of the TNM stage or EZH2 expression alone model.</p

Daunorubicin-containing CLL1-targeting nanomicelles have anti-leukemia stem cell activity in acute myeloid leukemia.

Patients with acute myeloid leukemia have a very poor prognosis related to a high rate of relapse and drug-related toxicity. The ability of leukemia stem cells (LSCs) to survive chemotherapy is primarily responsible for relapse, and eliminating LSCs is ultimately essential for cure. We developed novel disulfide-crosslinked CLL1-targeting micelles (DC-CTM), which can deliver high concentrations of daunorubicin (DNR) into both bulk leukemia cells and LSCs. Compared to free DNR, DC-CTM-DNR had a longer half-life, increased DNR area under the curve concentration by 11-fold, and exhibited a superior toxicity profile. In patient-derived AML xenograft models, DC-CTM-DNR treatment led to significant decreases in AML engraftment and impairment of secondary transplantation compared to control groups. Collectively, we demonstrate superior anti-LSC/AML efficacy, and preferable pharmacokinetic and toxicity profiles of DC-CTM-DNR compared to free DNR. DC-CTM-DNR has the potential to significantly improve treatment outcomes and reduce therapy-related morbidity and mortality for patients with AML

Kaplan-Meier analysis of disease-free survival (DFS) in renal cell carcinoma according to expression of the EZH2 or H3K27me3 score.

<p>(A), (D) all patients in the training set. (B), (E) patients with I+II stage disease in the training set. (C), (F) patients with III+IV stage disease in the training set. (G), (J) all patients in the validation set. (H), (K) patients with I+II stage disease in the validation set. (I), (L) patients with III+IV stage disease in the validation set. </p

Combination of cyclin-dependent kinase and immune checkpoint inhibitors for the treatment of bladder cancer

BackgroundPerturbation of the CDK4/6 pathway is frequently observed in advanced bladder cancer. We investigated the potential of targeting this pathway alone or in combination with chemotherapy or immunotherapy as a therapeutic approach for the treatment of bladder cancer METHODS: The genetic alterations of the CDK4/6 pathway in bladder cancer were first analyzed with The Cancer Genome Atlas database and validated in our bladder cancer patient-derived tumor xenografts (PDXs). Bladder cancer cell lines and mice carrying PDXs with the CDK4/6 pathway perturbations were treated with a CDK4/6 inhibitor palbociclib to determine its anticancer activity and the underlying mechanisms. The combination index method was performed to assess palbociclib and gemcitabine drug-drug interactions. Syngeneic mouse bladder cancer model BBN963 was used to assess whether palbociclib could potentiate anti-PD1 immunotherapy.ResultsOf the 413 bladder cancer specimens, 79.2% harbored pertubations along the CDK4/6 pathway. Palbociclib induced G0/G1 cell cycle arrest but with minimal apoptosis in vitro. In mice carrying PDXs, palbociclib treatment reduced tumor growth and prolonged survival from 14 to 32&nbsp;days compared to vehicle only controls (p = 0.0001). Palbociclib treatment was associated with a decrease in Rb phosphorylation in both cell lines and PDXs. Palbociclib and gemcitabine exhibited antagonistic cytotoxicity in vitro (CI &gt; 3) and in vivo, but palbociclib&nbsp;significantly enhanced the treatment efficacy of anti-PD1 immunotherapy and induced CD8+ T lymphocyte infiltration in syngeneic mouse models.ConclusionsThe CDK4/6 pathway is feasible as a potential target for the treatment of bladder cancer, especially in combination with immunotherapy. A CDK4/6 inhibitor should not be combined with gemcitabine