Resilience and vulnerabilities of tumor cells under purine shortage stress.

Purpose: Purine metabolism is a promising therapeutic target in cancer; however, how cancer cells respond to purine shortage, particularly their adaptation and vulnerabilities, remains unclear.

Experimental Design: Using the recently developed purine shortage-inducing prodrug DRP-104 and genetic approaches, we investigated the responses in prostate, lung, and glioma cancer models.

Results: We demonstrate that when de novo purine biosynthesis is compromised, cancer cells employ microtubules to assemble purinosomes, multi-protein complexes of de novo purine biosynthesis enzymes that enhance purine biosynthesis efficiency.

FMNL2/SRC-mediated androgen receptor translocation into the nucleus promotes enzalutamide resistance of prostate cancer.

Enzalutamide, a second-generation androgen receptor (AR) antagonist, has represented the association with improved overall survival in men with prostate cancer (PCa). However, PCa patients receiving enzalutamide will eventually develop resistance through various mechanisms without effective regimens. Here, we observed a higher level of formin-like 2 (FMNL2) in enzalutamide-resistant PCa cells.

Resilience and vulnerabilities of tumor cells under purine shortage stress.

Purine metabolism is a promising therapeutic target in cancer; however how cancer cells respond to purine shortage,particularly their adaptation and vulnerabilities, remains unclear. Using the recently developed purine shortage-inducing prodrug DRP-104 and genetic approaches, we investigated these responses in prostate, lung and glioma cancer models. We demonstrate that when de novo purine biosynthesis is compromised, cancer cells employ microtubules to assemble purinosomes, multi-protein complexes of de novo purine biosynthesis enzymes that enhance purine biosynthesis efficiency.

Monoacylglycerol lipase blockades the senescence-associated secretory phenotype by interfering with NF-κB activation and promotes docetaxel efficacy in prostate cancer.

Metabolic reprogramming and cellular senescence greatly contribute to cancer relapse and recurrence. In aging and treated prostate, persistent accumulating senescence-associated secretory phenotype (SASP) of cancer cells often limits the overall survival of patients. Novel strategic therapy with monoacylglycerol lipase (MGLL) upregulation that counters the cellular and docetaxel induced SASP might overcome this clinical challenge in prostate cancer (PCa).

Two-Stage Deep-Learning Classifier for Diagnostics of Lung Cancer Using Metabolites.

We developed a machine-learning system for the selective diagnostics of adenocarcinoma (AD), squamous cell carcinoma (SQ), and small-cell carcinoma lung (SC) cancers based on their metabolomic profiles. The system is organized as two-stage binary classifiers. The best accuracy for classification is 92%.

HOXB3 drives WNT-activation associated progression in castration-resistant prostate cancer.

Enabled resistance or innate insensitiveness to antiandrogen are lethal for castration-resistant prostate cancer (CRPC). Unfortunately, there seems to be little can be done to overcome the antiandrogen resistance because of the largely unknown mechanisms. In prospective cohort study, we found that HOXB3 protein level was an independent risk factor of PSA progression and death in patients with metastatic CRPC.

Circular RNAs in Prostate Cancer: Is it Time to Further Explore Liquid Biopsies?

Background: Although diagnosis and treatment of prostate cancer (PCa) have evolved rapidly in recent years, clinically significant molecular biomarkers are still needed to lower the mortality. Circular RNAs (circRNAs) are a poorly characterized component of PCa transcriptome. Recently, since the development of deep RNA sequencing and novel bioinformatic pipelines, emerging evidence suggests circRNAs to have diverse functions in the development and progression of PCa.

Identification of LAT/ZAP70 characterized immune subtypes of prostate cancer.

Background: While immunotherapy has shown potent efficacy in clinical practices, patient selection to receive checkpoint blockade is still challenging in prostate cancer (PCa). LAT and ZAP70 functions in lymphocyte activation and plays a critical role in T cell receptor (TCR) signal transduction. However, PCa genomic and clinical data regarding the role of LAT and ZAP70 are limited.

The Relationship Between Serum Folate Level and Residual Renal Function in CAPD Patients.

Objective: To investigate the relationship between serum folate (FA) levels and residual renal function (RRF) in continuous ambulatory peritoneal dialysis (CAPD) patients.

Methods: Clinical data were collected from 180 hospitalized patients who received CAPD regularly. Patients were divided into the FA deficiency group and the FA non-deficiency group according to serum FA level.

hsa_circ_0092339 acts as a molecular sponge in castration-resistant prostate cancer via the hsa-mir-940/ axis.

We aimed to determine whether intronic circRNA acts as a molecular sponge in castration-resistant prostate cancer (CRPC). A gene chip technique was used to conduct sequencing. A qPCR experiment was performed to verify the result.

Oral Hydrogen-Rich Water Alleviates Oxalate-Induced Kidney Injury by Suppressing Oxidative Stress, Inflammation, and Fibrosis.

To explore the theraputic effects and potential mechanisms of hydrogen-rich water (HRW) against oxalate-induced kidney injury. The mouse model of Calcium oxalate (CaOx) crystallization was established by feeding a soluble oxalate diet. Crystal deposition, tubular injury, fibrosis and reactive oxygen species (ROS) production in kidneys were examined by histology.

YAP1 plays a key role of the conversion of normal fibroblasts into cancer-associated fibroblasts that contribute to prostate cancer progression.

Background: Cancer-associated fibroblasts (CAFs) are an important part of the tumour microenvironment, and their functions are of great concern. This series of experiments aimed to explore how Yes-associated protein 1 (YAP1) regulates the function of stromal cells and how the normal fibroblasts (NFs) convert into CAFs in prostate cancer (PCa).

Methods: The effects of conditioned media from different fibroblasts on the proliferation and invasion of epithelial cells TrampC1 were examined.

Restoration of FKBP51 protein promotes the progression of castration resistant prostate cancer.

Background: As deregulation of androgen receptor (AR) signaling target genes is associated with tumorigenesis and the development of prostate cancer (PCa), AR signaling is the primary therapeutic target for PCa. Although patients initially responses to first-line androgen deprivation therapies (ADTs), most of them with advanced PCa progress to lethal castration-resistant prostate cancer (CRPC). Recent studies have suggested the molecular mechanisms by which AR elicit the robust up-regulation of the gene.

Impact of squamous differentiation on intravesical recurrence and prognosis of patients with upper tract urothelial carcinoma.

Background: The prognostic role of squamous differentiation in upper urinary tract urothelial carcinoma (UTUC) is still unclear. This article describes the impact of squamous differentiation on prognosis and intravesical recurrence of patients with primary UTUC treated with radical nephroureterectomy (RNU).

Methods: Totally, we retrieved (I) 669 histologically confirmed UTUC patients without histologic variants; (II) 101 UTUC patients with squamous differentiation in our institution, dating from April 2003 to April 2016.

A retrospective analysis of the correlation between AXL expression and clinical outcomes of patients with urothelial bladder carcinoma.

Background: Immunohistochemistry (IHC) analysis of primary tumors revealed that AXL expression is associated with survival in patients with different cancers. The objective of our study is to investigate the relationship between the expression of AXL and clinical outcomes of patients with bladder carcinoma (BC).

Methods: A total of 407 samples from The Cancer Genome Atlas (TCGA) database and 203 patients with clinical and pathological diagnosis of BC in our hospital were used to assess the association of AXL and clinical outcomes of BC patients.

KIF20A Affects the Prognosis of Bladder Cancer by Promoting the Proliferation and Metastasis of Bladder Cancer Cells.

Objective: To investigate the expression of kinesin family member 20A (KIF20A) in bladder cancer, the effect of KIF20A on the proliferation and metastasis of bladder cancer cells, and the effect of KIF20A expression on the prognosis of bladder cancer patients.

Methods: Bladder cancer tissue and its adjacent tissues were collected from tumour patients. The mRNA and protein expression levels of KIF20A in the tissue samples were detected by qRT-PCR and western blot.

LncRNA PCAT1 activates AKT and NF-κB signaling in castration-resistant prostate cancer by regulating the PHLPP/FKBP51/IKKα complex.

In PTEN-deficient prostate cancers, AKT signaling may be activated upon suppression of androgen receptor signaling. Activation of AKT as well as NF-κB signaling involves a key regulatory protein complex containing PHLPP, FKBP51 and IKKα. Here, we report a critical role of lncRNA PCAT1 in regulating the PHLPP/FKBP51/IKKα complex and progression of castration-resistant prostate cancer (CRPC).

High Expression of KIF22/Kinesin-Like DNA Binding Protein (Kid) as a Poor Prognostic Factor in Prostate Cancer Patients.

BACKGROUND Kid (kinesin-like DNA binding protein), a member of microtubule-dependent molecular motor proteins, also known as KIF22, is reported to be associated with carcinogenesis and cancer progression in different types of malignant tumor, but the biologic behavior and clinical outcome of KIF22 in prostate cancer (PCa) has not been well studied. This study aimed to analyze the association between KIF22 and clinical outcome in PCa patients. MATERIAL AND METHODS The expression of KIF22 in tumor specimens compared with paired paracancerous tissue from 114 patients undergoing radical prostatectomy was detected by immunohistochemistry; results were verified using The Cancer Genome Atlas (TCGA) database.

Sox5 contributes to prostate cancer metastasis and is a master regulator of TGF-β-induced epithelial mesenchymal transition through controlling Twist1 expression.

Background: Metastatic castration-resistant prostate cancer (mCRPC) is one of the main contributors to the death of prostate cancer patients. To date, the detailed molecular mechanisms underlying mCRPC are unclear. Given the crucial role of epithelial-mesenchymal transition (EMT) in cancer metastasis, we aimed to analyse the expression and function of Transforming growth factor-beta (TGF-β) signal-associated protein named Sox5 in mCRPC.

Squamous differentiation in patients with superficial bladder urothelial carcinoma is associated with high risk of recurrence and poor survival.

Background: The independent prognostic role of squamous differentiation in pT1 bladder urothelial carcinoma has not been reported in previous studies. This article describes the impact of squamous differentiation on tumor recurrence and survival, and whether this histologic variant could indeed alter definitive treatment, based on single center-based retrospective data.

Methods: Totally, we retrieved (1)1449 histologically confirmed pT1 bladder urothelial carcinoma patients without histologic variants; (2)227 pT1 bladder urothelial carcinoma patients with squamous differentiation in our institution, from May 2004 to Oct 2015.

Clinicopathological study on thyroid follicular carcinoma-like renal tumor related to serious hypertension: Case report and review of the literature.

Rationale: Thyroid carcinoma-like tumor of the kidney (TLFCK) is an extremely rare variant of renal cell carcinoma. Most cases were incidentally found, while we report the first case of TLFCK presented with hypertension.

Patient Concerns: A 25-year-old woman was admitted to our hospital presenting with hypertension for ∼20 months, without gross hematuria, weight loss, and flank pain.