Efficacy, Safety, and Tolerability of Tivozanib in Heavily Pretreated Patients With Advanced Clear Cell Renal Cell Carcinoma.

BACKGROUND: Tivozanib has been approved as a third-line or later therapy for advanced renal cell carcinoma based on the TIVO-3 trial, which was conducted before immune checkpoint therapies (ICT), cabozantinib, and lenvatinib/everolimus became incorporated in the current sequential treatment paradigm for advanced clear cell RCC (ccRCC). METHODS: We performed a retrospective study of patients with advanced ccRCC treated with tivozanib at MD Anderson Cancer Center during 6/2021-7/2023. A blinded radiologist assessed tumor response by RECIST v1.1. We assessed overall response rate (ORR), clinical benefit rate (CBR) [percentage of all treated patients who achieved radiologic response or stable disease (SD) for ≥ 6 months], progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Of 30 analyzed patients, 23% had performance status ≥ 2; 47% had International Metastatic RCC Database Consortium (IMDC) poor-risk disease. Median number of prior therapies was 4 (range 1-8). All patients received prior ICT, 87% cabozantinib and 60% lenvatinib ± everolimus. Of 26 evaluable patients, 2 patients had confirmed partial response (ORR 7.7%); 5 patients had SD for ≥ 6 months (CBR 23.3%). Median PFS was 3.8 months (range 0.7-13.9); median OS was 14.1 months (range 0.3-28.5). Fifteen patients (50%) had ≥ 1 treatment-related adverse event (TRAE). There were 6 grade ≥ 3 TRAEs [hypertension, congestive heart failure (3), mucositis, and GI perforation (grade 5)]. CONCLUSIONS: In this cohort of heavily pretreated patients with advanced ccRCC, tivozanib yielded a modest clinical benefit in a minority of patients who received prior ICT, cabozantinib, and lenvatinib ± everolimus. TRAEs were consistent with previously published reports.

An intrinsic CRF signaling system within the optic tectum.

Previous work indicates that CRF administration inhibits visually guided feeding in amphibians. We used the African clawed frog Xenopus laevis to examine the hypothesis that CRF acts as a neurotransmitter in the optic tectum, the major brain area integrating the visual and premotor pathways regulating visually guided feeding in anurans. Reverse transcriptase PCR revealed that cells in the optic tectum express mRNA for CRF and the CRF R1 receptor but not the CRF R2 receptor. Radioligand binding studies indicated that specific binding of [(125)I]-Tyr-oCRF to tectal cell membranes can be displaced by the CRF R1 antagonists antalarmin or NBI-27914. CRF increased the expression of mRNA encoding regulator of G-protein signaling 2 (rgs2) in tectal explants and this effect was blocked by antalarmin. CRF had no effect on basal glutamate or gamma-aminobutyric acid (GABA) secretion but inhibited secretion of norepinephrine from tectal explants, an effect that completely blocked by antalarmin. Using a homologous radioimmunoassay we determined that CRF release from tectal explants in vitro was potassium- and calcium-dependent. Basal and depolarization-induced CRF secretion was greater from optic tectum than hypothalamus/thalamus, telencephalon, or brainstem. We concluded that the optic tectum possesses a CRF signaling system that may be involved in modulating communication between sensory and motor pathways involved in food intake.

US, MRI, CT Performance and Interpretation of Uterine Masses.

Uterine masses are commonly encountered as incidental findings during cross-sectional imaging or when individuals present with symptoms such as pain and bleeding. The World Health Organization categorizes tumors of the uterine corpus into 5 distinct groups: endometrial epithelial tumors and their precursors, tumor-like growths, mesenchymal uterine tumors, tumors with a combination of epithelial and mesenchymal elements, and various other types of tumors. The primary imaging method for assessing uterine abnormalities is transvaginal ultrasound. However, magnetic resonance imaging (MRI) can be employed to enhance the visualization of soft tissues, enabling a more detailed characterization of uterine masses. This article aims to outline the imaging features of both benign and malignant uterine masses using ultrasound, MRI, and computed tomography.

Unusual Metastatic Prostate Cancer in Subcarinal Lymph Node and Peritoneal Nodule Found on 18 F-PSMA PET/CT With Rising PSA of 0.4 ng/mL.

ABSTRACT: A 79-year-old man with metastatic prostate cancer underwent radical prostatectomy and bilateral lymph node dissection and received multiple lines of systematic treatment for his biopsy-proven peritoneal carcinomatosis. During the disease course, his prostate-specific antigen rose from 0.1 ng/mL to 0.4 ng/mL in 4 months, and testosterone level was <3 ng/dL. Workup 18 F-DCFPyL PET/CT showed unusual prostate-specific membrane antigen-avid, 1.1-cm subcarinal lymph node and a 0.8-cm peritoneal nodule, which were not hypermetabolic on an 18 F-FDG PET/CT 6 days later. This case illustrated the sensitivity for 18 F-DCFPyL PET/CT in detecting metastatic castration-resistant prostate cancer.

High throughput RNA sequencing utility for diagnosis and prognosis in colon diseases.

RNA sequencing is the use of high throughput next generation sequencing technology to survey, characterize, and quantify the transcriptome of a genome. RNA sequencing has been used to analyze the pathogenesis of several malignancies such melanoma, lung cancer, and colorectal cancer. RNA sequencing can identify differential expression of genes (DEG's), mutated genes, fusion genes, and gene isoforms in disease states. RNA sequencing has been used in the investigation of several colorectal diseases such as colorectal cancer, inflammatory bowel disease (ulcerative colitis and Crohn's disease), and irritable bowel syndrome.