CCT251545 enhances drug delivery and potentiates chemotherapy in multidrug-resistant cancers by Rac1-mediated macropinocytosis.

It was well known that P-glycoprotein (P-gp/ABCB1) is a master regulator of multidrug resistance (MDR) in cancers. However, the clinical benefit from blocking this pathway remains inconclusive, which motivates a paradigm shift towards alternative strategies for enhancing drug influx. Using a patient-derived organoid (PDO)-based drug screening platform, we report that the combined use of chemotherapy and CCT251545 (CCT) displays robust synergistic effect against PDOs and reduces proliferation of MDR cancer cells in vitro, and results in regression of xenograft tumors, reductions in metastatic dissemination and recurrence rate in vivo.

Macrophage-Specific Cathepsin as a Marker Correlated with Prognosis and Tumor Microenvironmental Characteristics of Clear Cell Renal Cell Carcinoma.

Background: Cathepsin Z (CTSZ) is a cathepsin family member that plays a dual role in the adhesion and migration of immune and tumor cells.

Methods: The expression pattern of CTSZ in clear cell renal cell carcinoma (ccRCC) was observed by immunohistochemistry and validated by using double-labeling immunofluorescence. Publicly available single-cell sequencing data was used to further define the cell type-specific CTSZ expression in ccRCC.

Identification of an amino acid metabolism-associated gene signature predicting the prognosis and immune therapy response of clear cell renal cell carcinoma.

Background: The upregulation of amino acid metabolism is an essential form of metabolic reprogramming in cancer. Here, we developed an amino acid metabolism signature to predict prognosis and anti-PD-1 therapy response in clear cell renal cell carcinoma (ccRCC).

Methods: According to the amino acid metabolism-associated gene sets contained in the Molecular Signature Database, consensus clustering was performed to divide patients into two clusters.

Metabolic Adaptation-Mediated Cancer Survival and Progression in Oxidative Stress.

Undue elevation of ROS levels commonly occurs during cancer evolution as a result of various antitumor therapeutics and/or endogenous immune response. Overwhelming ROS levels induced cancer cell death through the dysregulation of ROS-sensitive glycolytic enzymes, leading to the catastrophic depression of glycolysis and oxidative phosphorylation (OXPHOS), which are critical for cancer survival and progression. However, cancer cells also adapt to such catastrophic oxidative and metabolic stresses by metabolic reprograming, resulting in cancer residuality, progression, and relapse.

Integrated Analysis of Energy Metabolism Signature-Identified Distinct Subtypes of Bladder Urothelial Carcinoma.

Bladder urothelial carcinoma (BLCA) is the most common type of bladder cancer. In this study, the correlation between the metabolic status and the outcome of patients with BLCA was evaluated using data from the Cancer Genome Atlas and Gene Expression Omnibus datasets. The clinical and transcriptomic data of patients with BLCA were downloaded from the Cancer Genome Atlas and cBioPortal datasets, and energy metabolism-related gene sets were obtained from the Molecular Signature Database.

Reoperation for Recurrent Adrenocortical Carcinoma: A Systematic Review and Pooled Analysis of Population-Based Studies.

Background: Adrenocortical carcinoma (ACC) is a rare neoplasm with a high recurrence rate. This study aimed to assess the role of surgery in the clinical management of recurrent ACC.

Methods: The PubMed, Embase, Web of Science, and Cochrane Library databases were searched, and the hazard ratios were pooled.

Inhibition of NPC1L1 disrupts adaptive responses of drug-tolerant persister cells to chemotherapy.

Entering a drug-tolerant persister (DTP) state of cancer cells is a transient self-adaptive mechanism by which a residual cell subpopulation accelerates tumor progression. Here, we identified the acquisition of a DTP phenotype in multidrug-resistant (MDR) cancer cells as a tolerance response to routine combination treatment. Characterization of MDR cancer cells with a DTP state by RNA-seq revealed that these cells partially prevented chemotherapy-triggered oxidative stress by promoting NPC1L1-regulated uptake of vitamin E.

Nanoparticle-Based RNAi Therapeutics Targeting Cancer Stem Cells: Update and Prospective.

Cancer stem cells (CSCs) are characterized by intrinsic self-renewal and tumorigenic properties, and play important roles in tumor initiation, progression, and resistance to diverse forms of anticancer therapy. Accordingly, targeting signaling pathways that are critical for CSC maintenance and biofunctions, including the Wnt, Notch, Hippo, and Hedgehog signaling cascades, remains a promising therapeutic strategy in multiple cancer types. Furthermore, advances in various cancer omics approaches have largely increased our knowledge of the molecular basis of CSCs, and provided numerous novel targets for anticancer therapy.

Metalated Porous Phenanthroline-Based Polymers as Efficient Heterogeneous Catalysts for Regioselective C-H Activation of Heteroarenes.

Direct C-H bond activation of heterocycles as a step-economical and environmentally friendly approach to build the heterobiaryls motifs is highly attractive, but it still has a challenge to design and prepare a cheap and regioselective heterogeneous catalyst. To tackle this challenge, we have introduced Ni species into a porous phenanthroline-based organic polymer donated as POP-Phen@Ni. This heterogeneous catalyst shows excellent catalytic performances in regioselective C-H activation of heterocycles, even better than those of the corresponding homogenous catalyst.

Porous Organic Phenanthroline-Based Polymer as an Efficient Transition-Metal-Free Heterogeneous Catalyst for Direct Aromatic C-H Activation.

Direct C-H bond transformation has been regarded as one of the most important areas in organic synthesis in both academia and industry. However, the heterogeneous transition-metal-free catalysis of direct C-H bond transformation has remained a contemporary challenge. To tackle this challenge, we designed and constructed a porous phenanthroline-based polymer (namely POP-Phen) via free radical polymerization of vinyl-functionalized phenanthroline monomers.

Clinical significance of prognostic nutritional index in renal cell carcinomas.

Prognostic nutritional index (PNI) could reflect the nutrition and inflammation status in cancer patients. This study aims to identify the prognostic significance of PNI in patients with renal cell carcinoma (RCC).A total of 694 RCC patients from our institution were included in this study.

Nomogram predicting survival to assist decision-making of radical prostatectomy in patients with metastatic prostate cancer.

Background: Radical prostatectomy (RP) has heterogeneous effects on survival of patients with metastatic prostate cancer (mPCa). A reliable model to predict risk of cancer-specific mortality (CSM) and the potential benefit derived from RP is needed.

Methods: Patients diagnosed with mPCa were identified using the Surveillance, Epidemiology, and End Results database (2004-2015) and categorized in RP versus nonlocal treatment (NLT).

Operative intervention for recurrence of adrenocortical carcinoma: A single-center experience.

Introduction: Adrenocortical carcinoma is a rare endocrine malignancy with a high recurrence rate. The aim of this study was to evaluate the role of surgery for patients with local or distant recurrent adrenocortical carcinoma and to attempt to identify prognostic features related to survival benefit in patients undergoing resection of recurrence.

Methods: The data of 47 patients with recurrent adrenocortical carcinoma in West China Hospital, Sichuan, China, between 2009 and 2019 were retrospectively collected.

Clinicopathological and Prognostic Characteristics of CD276 (B7-H3) Expression in Adrenocortical Carcinoma.

Background: Adrenocortical carcinoma (ACC) is a rare malignant endocrine tumor with a high tumor recurrence rate and poor postoperative survival. Recent studies suggest that CD276- (B7-H3) targeted therapy represents a promising therapeutic option for solid tumors. However, little is known about the expression status of CD276 or its association with progression and prognosis of ACC.

The clinical utility of 'GRAS' parameters in stage I-III adrenocortical carcinomas: long-term data from a high-volume institution.

Background: Adrenocortical carcinoma (ACC) is a rare cancer with poor survival. We sought to identify prognostic factors and assess its clinical utility in postoperative management of nonmetastatic ACC.

Methods: We included 65 patients who underwent adrenalectomy and clinicopathological diagnosed as European Network for the Study of Adrenal Tumors (ENSAT) stage I-III ACC in our center from 2009 to 2017.

Expression of FSCN1 and FOXM1 are associated with poor prognosis of adrenocortical carcinoma patients.

Background: Adrenocortical carcinoma (ACC) is a rare malignant endocrine tumour. Due to a high tumour recurrence rate, the post-operative overall survival (OS) and disease-free survival (DFS) of ACCs is limited. Our research aims to identify the role of the epithelial-mesenchymal transition (EMT) related genes FSCN1 and FOXM1 in the tumour microenvironment and assess their prognostic value in ACCs.

Location matters: cooperativity of catalytic partners in porous organic polymers for enhanced CO transformation.

Herein, we show that by following molecular engineering of the inter-site distance between the two functionalities in porous organic materials, it is possible to enable them to work in a concerted manner. Specifically, the activity can be amplified by the placement of the hydroxyl group in the meta position of the phosphonium salts in the representative cycloaddition of epoxides and CO.

Bio-inspired creation of heterogeneous reaction vessels via polymerization of supramolecular ion pair.

Precise control of the outer-sphere environment around the active sites of heterogeneous catalysts to modulate the catalytic outcomes has long been a challenge. Here, we demonstrate how this can be fulfilled by encapsulating catalytic components into supramolecular capsules, used as building blocks for materials synthesis, whereby the microenvironment of each active site is tuned by the assembled wall. Specifically, using a cationic template equipped with a polymerizable functionality, anionic ligands can be encapsulated by ion pair-directed supramolecular assembly, followed by construction into porous frameworks.

Increased expression of miR-155 correlates with abnormal allograft status in solid organ transplant patients and rat kidney transplantation model.

Aims: Increasing evidence has shown the diagnostic value of miR-155 in organ transplantation. The dysregulation of miR-155 is reported to be associated with development of acute or chronic complications in solid organ transplant recipients. Here, we summarized related evidence to explore the correlation between the dysregulation of miR-155 and various allograft dysfunction in transplant recipients, and verified the dynamic change of miR-155 level in acute rejection (AR) using a rat renal transplantation model.

Reaction Environment Modification in Covalent Organic Frameworks for Catalytic Performance Enhancement.

Herein, we show how the spatial environment in the functional pores of covalent organic frameworks (COFs) can be manipulated in order to exert control in catalysis. The underlying mechanism of this strategy relies on the placement of linear polymers in the pore channels that are anchored with catalytic species, analogous to outer-sphere residue cooperativity within the active sites of enzymes. This approach benefits from the flexibility and enriched concentration of the functional moieties on the linear polymers, enabling the desired reaction environment in close proximity to the active sites, thereby impacting the reaction outcomes.

Knockdown of ribosomal protein S15A inhibits human kidney cancer cell growth in vitro and in vivo.

Ribosomal protein S15A (RPS15A), a member of the ribosomal protein gene family, was demonstrated to be closely associated with tumorigenesis in multiple human malignancies. Nevertheless, the role of RPS15A in the progression of renal cell carcinoma (RCC) remains unknown. In the present study, by comparing the publicly available data from RCC tissues and reverse transcription‑quantitative polymerase chain reaction results, it was identified that RPS15A was upregulated in RCC tissues and cell lines (P<0.

Early post-operative serum albumin level predicts survival after curative nephrectomy for kidney cancer: a retrospective study.

Background: Previous studies have shown that albumin-related systemic inflammation is associated with the long-term prognosis of cancer, but the clinical significance of an early (≤ 7 days) post-operative serum albumin level has not been well-documented as a prognostic factor in patients with renal cell cancer.

Methods: We retrospectively included patients hospitalized for kidney cancer from January 2009 to May 2014. First, the receiver operating characteristic analysis was used to define the best cut-off of an early post-operative serum albumin level in determining the prognosis, from which survival analysis was performed.