Lidocaine induces apoptosis in head and neck squamous cell carcinoma through activation of bitter taste receptor T2R14.

Head and neck squamous cell carcinomas (HNSCCs) have high mortality and significant treatment-related morbidity. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life. Bitter taste receptors (T2Rs) are expressed in HNSCCs, and T2R activation can induce apoptosis.

Clonal hematopoiesis and risk of prostate cancer in large samples of European ancestry men.

Little is known regarding the potential relationship between clonal hematopoiesis (CH) of indeterminate potential (CHIP), which is the expansion of hematopoietic stem cells with somatic mutations, and risk of prostate cancer, the fifth leading cause of cancer death of men worldwide. We evaluated the association of age-related CHIP with overall and aggressive prostate cancer risk in two large whole-exome sequencing studies of 75 047 European ancestry men, including 7663 prostate cancer cases, 2770 of which had aggressive disease, and 3266 men carrying CHIP variants. We found that CHIP, defined by over 50 CHIP genes individually and in aggregate, was not significantly associated with overall (aggregate HR = 0.

Impact of sweet, umami, and bitter taste receptor (TAS1R and TAS2R) genomic and expression alterations in solid tumors on survival.

Originally identified on the tongue for their chemosensory role, the receptors for sweet, umami, and bitter taste are expressed in some cancers where they regulate important cellular processes including apoptosis and proliferation. We examined DNA mutations (n = 5103), structural variation (n = 7545), and expression (n = 6224) of genes encoding sweet or umami receptors (TAS1Rs) and bitter receptors (TAS2Rs) in 45 solid tumors subtypes compared to corresponding normal tissue using The Cancer Genome Atlas and the Genotype Tissue Expression Project databases. Expression of TAS1R and TAS2R genes differed between normal and cancer tissue, and nonsilent mutations occurred in many solid tumor taste receptor genes (~ 1-7%).

Impact of birth season on second-to-fourth digit ratio, prostate volume, and prostate cancer.

Purpose: The second-to-fourth digit ratio (digit ratio), which is determined , is associated with exposure to visible sunlight during early pregnancy and the season of birth. The digit ratio is also associated with benign prostatic hyperplasia (BPH) and prostate cancer. This suggests that BPH and prostate cancer may be related to the birth season.

T2R bitter taste receptors regulate apoptosis and may be associated with survival in head and neck squamous cell carcinoma.

Better management of head and neck squamous cell carcinomas (HNSCCs) requires a clearer understanding of tumor biology and disease risk. Bitter taste receptors (T2Rs) have been studied in several cancers, including thyroid, salivary, and GI, but their role in HNSCC has not been explored. We found that HNSCC patient samples and cell lines expressed functional T2Rs on both the cell and nuclear membranes.

Genomic, Transcriptomic, and Proteomic Profiling of Metastatic Breast Cancer.

Purpose: Metastatic breast cancer (MBC) is not curable and there is a growing interest in personalized therapy options. Here we report molecular profiling of MBC focusing on molecular evolution in actionable alterations.

Experimental Design: Sixty-two patients with MBC were included.

A novel patient-derived orthotopic xenograft model of esophageal adenocarcinoma provides a platform for translational discoveries.

Mouse models of gastroesophageal junction (GEJ) cancer strive to recapitulate the intratumoral heterogeneity and cellular crosstalk within patient tumors to improve clinical translation. GEJ cancers remain a therapeutic challenge due to the lack of a reliable mouse model for preclinical drug testing. In this study, a novel patient-derived orthotopic xenograft (PDOX) was established from GEJ cancer via transabdominal surgical implantation.

Sonographic findings of mass-forming extramammary Paget's disease in the scrotum.

Extramammary Paget's disease (EMPD) is a rare cutaneous malignancy involving the scrotum and may be confused with other scrotal malignancy. We describe the sonographic findings of an extremely rare case of mass-forming EMPD of the scrotal wall. Ultrasonography, which shows mild heterogeneous hyperechoic masses with a stalk connected to the dermis, can help predict the depth of vertical invasion of the lesion.

Hybrid oncocytic/chromophobe renal tumors are molecularly distinct from oncocytoma and chromophobe renal cell carcinoma.

Hybrid oncocytic/chromophobe tumor (HOCT) of the kidney represents a poorly understood clinicopathologic entity with pathologic features that overlap between benign renal oncocytoma (RO) and malignant chromophobe renal cell carcinoma (ChRCC). Consequently, characterization of HOCT and its separation from the foregoing entities are clinically important. The aim of this study was to describe the pathologic and molecular features of HOCT and to compare them with those of RO and ChRCC.

Adaptive responses in a PARP inhibitor window of opportunity trial illustrate limited functional interlesional heterogeneity and potential combination therapy options.

Poly (ADP-ribose) polymerase inhibitor (PARPi)-based combination therapies are demonstrating efficacy in patients, however, identifying the right combination for the right patient remains a critical challenge. Thus, it is urgent to develop approaches able to identify patients likely to benefit from specific combination therapies. Several groups, including ours, have demonstrated that targeting adaptive responses induced by PARPi increases depth and duration of response.

Sequential Therapy with PARP and WEE1 Inhibitors Minimizes Toxicity while Maintaining Efficacy.

We demonstrate that concurrent administration of poly(ADP-ribose) polymerase (PARP) and WEE1 inhibitors is effective in inhibiting tumor growth but poorly tolerated. Concurrent treatment with PARP and WEE1 inhibitors induces replication stress, DNA damage, and abrogates the G DNA damage checkpoint in both normal and malignant cells. Following cessation of monotherapy with PARP or WEE1 inhibitors, effects of these inhibitors persist suggesting that sequential administration of PARP and WEE1 inhibitors could maintain efficacy while ameliorating toxicity.

Integrated transcriptomic-genomic tool Texomer profiles cancer tissues.

Profiling of both the genome and the transcriptome promises a comprehensive, functional readout of a tissue sample, yet analytical approaches are required to translate the increased data dimensionality, heterogeneity and complexity into patient benefits. We developed a statistical approach called Texomer ( https://github.com/KChen-lab/Texomer ) that performs allele-specific, tumor-deconvoluted transcriptome-exome integration of autologous bulk whole-exome and transcriptome sequencing data.

Use of Targeted Next-Generation Sequencing to Identify Activating Hot Spot Mutations in Cherry Angiomas.

Importance: Shared gene variants in benign-malignant process pairs, such as BRAF mutations common to benign nevi and melanoma, are associated with differing phenotypic manifestations. Study of gene mechanisms underlying cherry angioma may uncover previously unknown disease relationships.

Objective: To identify somatic mutations present in cherry angioma specimens by using targeted next-generation sequencing.

The Efficacy of Early Extracorporeal Shockwave Lithotripsy for the Treatment of Ureteral Stones.

Purpose: To determine the efficacy of early extracorporeal shockwave lithotripsy (e-ESWL) in colic patients with ureteral stones and the patient criteria for the most effective e-ESWL.

Materials And Methods: 335 patients who received ESWL due to ureteral stone, were divide in two groups: e-ESWL and d-ESWL by the critical cut-off point. we performed the sensitivity and specificity cut-off analyses to identified the critical cut off point.

Survival Outcomes by Mutation Status in Metastatic Breast Cancer.

Purpose: We sought to determine the significant genomic alterations in patients with metastatic breast cancer (MBC), and survival outcomes in common genotypes.

Patients And Methods: High-depth next generation sequencing was performed for 202 genes in tumor and normal DNA from 257 patients with MBC, including 165 patients with ER/PR+ HER2- (hormone receptor positive, HR+ positive), 32 patients with HER2+ and 60 patients with triple negative (ER/PR/HER2-) cancer. Kaplan Meier survival analysis was performed in our discovery set, in breast cancer patients analyzed in The Cancer Genome Atlas, and in a separate cohort of 98 patients with MBC who underwent clinical genomic testing.

Urology as rehabilitation medicine: a literature review.

As a urologist, we usually encounter with two representative functional behaviors, namely, voiding and sexual function. These are not only important but also complex and synchronized so if these functions are impaired, patients need active functional rehabilitation to recover. These functional impairments should be recognized and corrected early because they could not only cause direct damage to the affected functions but also have harmful consecutive consequences such as kidney damage due to voiding abnormality and self-esteem damage due to decreased sexual function.

Cancer driver mutation prediction through Bayesian integration of multi-omic data.

Identification of cancer driver mutations is critical for advancing cancer research and personalized medicine. Due to inter-tumor genetic heterogeneity, many driver mutations occur at low frequencies, which make it challenging to distinguish them from passenger mutations. Here, we show that a novel Bayesian hierarchical modeling approach, named rDriver can achieve enhanced prediction accuracy by identifying mutations that not only have high functional impact scores but also are associated with systemic variation in gene expression levels.

Pathogenic Germline Variants in 10,389 Adult Cancers.

We conducted the largest investigation of predisposition variants in cancer to date, discovering 853 pathogenic or likely pathogenic variants in 8% of 10,389 cases from 33 cancer types. Twenty-one genes showed single or cross-cancer associations, including novel associations of SDHA in melanoma and PALB2 in stomach adenocarcinoma. The 659 predisposition variants and 18 additional large deletions in tumor suppressors, including ATM, BRCA1, and NF1, showed low gene expression and frequent (43%) loss of heterozygosity or biallelic two-hit events.

The Association of A Number of Risk Factors With Depression in Patients With Prostate Cancer Undergoing Androgen Deprivation Therapy.

Purpose: To identify factors affecting depressive symptoms in patients undergoing androgen-deprivation therapy (ADT) to treat prostate cancer.

Materials And Methods: The patients with prostate cancer visiting the psychiatry department without referral because of depressive symptoms while undergoing ADT participated. To assess depressive symptoms, the Beck Depression Inventory (BDI) was used.

Enucleated Weight/Enucleation Time, Is It Appropriate for Estimating Enucleation Skills for Holmium Laser Enucleation of the Prostate? A Consideration of Energy Consumption.

Purpose: To date, the parameters for evaluating enucleation efficiency have only considered enucleation time, although operators simultaneously consume both time and energy during holmium laser enucleation of the prostate. This study was undertaken to find a better way of assessing enucleation skills, considering both enucleation time and consumed energy.

Materials And Methods: One hundred (n=100) consecutive patients who underwent holmium laser enucleation of the prostate from April 2012 to April 2014 by a single surgeon were enrolled.

Larger Testicular Volume Is Independently Associated with Favorable Indices of Lung Function.

Background: Men with chronic obstructive pulmonary disease, have reduced endogenous testosterone levels, but the relationship between pulmonary function and endogenous testosterone levels, is inconsistent. Testicular volume is a known indicator of endogenous testosterone levels, male fertility, and male potency. In the present study, the authors investigated the relationship, between testicular volume and lung function.

Sarcomatoid Renal Cell Carcinoma Has a Distinct Molecular Pathogenesis, Driver Mutation Profile, and Transcriptional Landscape.

Sarcomatoid renal cell carcinoma (SRCC) ranks among the most aggressive clinicopathologic phenotypes of RCC. However, the paucity of high-quality, genome-wide molecular examinations of SRCC has hindered our understanding of this entity. We interrogated the mutational, copy number, and transcriptional characteristics of SRCC and compared these data with those of nonsarcomatoid RCC (RCC).

Comprehensive Genomic Characterization of Upper Tract Urothelial Carcinoma.

Background: Upper urinary tract urothelial cancer (UTUC) may have unique etiologic and genomic factors compared to bladder cancer.

Objective: To characterize the genomic landscape of UTUC and provide insights into its biology using comprehensive integrated genomic analyses.

Design, Setting, And Participants: We collected 31 untreated snap-frozen UTUC samples from two institutions and carried out whole-exome sequencing (WES) of DNA, RNA sequencing (RNAseq), and protein analysis.