Acylhydrazone-based reversibly photoswitchable ion pair transporter with OFF-ON cotransport activity.

The cellular membrane transport of physiologically important cations and anions is omnipresent and regulates different physiological functions. Whereas a notable number of cation-anion transporters are being developed to transport salts across the membrane, developing an artificial cation-anion symporter with stimulus-responsive activities is an immense obstacle. Herein, for the first time, we report reversibly photoswitchable acylhydrazone-based transporter 2 that has distinctive OFF-ON cation-anion co-transport abilities.

Clinicopathologic and Molecular Characterization of Inflammatory Bowel Disease-Associated Neuroendocrine Carcinomas and Mixed Neuroendocrine-Non-Neuroendocrine Neoplasms.

The pathogenesis of neuroendocrine carcinomas (NECs) and mixed neuroendocrine-non-neuroendocrine neoplasms (MiNENs) in the gastrointestinal tract remains poorly understood. This study aims to characterize the clinicopathologic and molecular features of NEC/MiNEN in patients with inflammatory bowel disease (IBD). Eighteen surgically resected IBD-associated intestinal carcinomas with a minimum of 30% neuroendocrine component were collected from 6 academic centers and compared with a control group of 12 IBD-associated carcinomas lacking neuroendocrine differentiation.

Real world predictors of response and 24-month survival in high-grade TP53-mutated myeloid neoplasms.

Current therapies for high-grade TP53-mutated myeloid neoplasms (≥10% blasts) do not offer a meaningful survival benefit except allogeneic stem cell transplantation in the minority who achieve a complete response to first line therapy (CR1). To identify reliable pre-therapy predictors of complete response to first-line therapy (CR1) and outcomes, we assembled a cohort of 242 individuals with TP53-mutated myeloid neoplasms and ≥10% blasts with well-annotated clinical, molecular and pathology data. Key outcomes examined were CR1 & 24-month survival (OS24).

Columnar Cell Thyroid Carcinoma: A Heterogeneous Entity Demonstrating Overlap Between Papillary Thyroid Carcinoma and Follicular Neoplasms.

Background: Columnar cell papillary thyroid carcinoma (CC-PTC) is a morphologic subtype of papillary thyroid carcinoma with a variable prognosis. It is characterized by neoplastic thyroid follicular-derived cells with pseudostratified columnar morphology arranged in papillary or follicular structures with supranuclear or subnuclear vacuoles. The molecular profile of this subtype has only recently come under scrutiny, with mixed results.

Uterine Inflammatory Myofibroblastic Tumors: p16 as a Surrogate for CDKN2A Deletion and Predictor of Aggressive Behavior.

Uterine inflammatory myofibroblastic tumors (IMTs) are rare mesenchymal neoplasms of uncertain malignant potential. Aside from the recently described risk stratification score, which has not been validated by other studies, and rare reports of aberrant p16 expression in malignant tumors, there are no criteria to reliably predict behavior. Herein, we evaluated the clinicopathologic features and p16 expression patterns in 30 IMTs, with genomic profiling performed in a subset (13 malignant, 3 benign).

Lung adenocarcinomas with isolated TP53 mutation: A comprehensive clinical, cytopathologic and molecular characterization.

Background: TP53 mutation is present in about 50.8% of lung adenocarcinomas, frequently in combination with other genetic alterations. However, a rare subset harbors the TP53 mutation alone.

Sequential tumor molecular profiling identifies likely germline variants.

Purpose: To identify likely germline DNA variants from sequential tumor profiling data from hematopoietic malignancies (HMs).

Methods: The coefficient of variance was calculated from variant allele frequency of next-generation sequencing assays. Variants' likelihood of being germline was ranked on a 1 to 5 scale.

Socioeconomic determinants of the biology and outcomes of acute lymphoblastic leukemia in adults.

Various socioeconomic and biologic factors affect cancer health disparities and differences in health outcomes. To better characterize the socioeconomic vs biologic determinants of acute lymphoblastic leukemia (ALL) outcomes, we conducted a single-institution, retrospective analysis of adult patients with ALL treated at the University of Chicago (UChicago) from 2010 to 2022 and compared our outcomes with the US national data (the Surveillance, Epidemiology, and End Results [SEER] database). Among 221 adult patients with ALL treated at UChicago, BCR::ABL1 was more frequent in patients with higher body mass index (BMI; odds ratio [OR], 7.

Synthesis and pharmacological evaluation of 1,3-diaryl substituted pyrazole based (thio)urea derivatives as potent antimicrobial agents against multi-drug resistant and .

The urgent development of newer alternatives has been deemed a panacea for tackling emerging antimicrobial resistance effectively. Herein, we report the design, synthesis, and biological evaluation of 1,3-diaryl substituted pyrazole-based urea and thiourea derivatives as antimicrobial agents. Preliminary screening results revealed that compound 7a (3,4-dichlorophenyl derivative) exhibited potent activity against (MIC = 0.

Identification of CYP3A4 inhibitors as potential anti-cancer agents using pharmacoinformatics approach.

Biguanide derivatives exhibit a wide variety of therapeutic applications, including anti-cancer effects. Metformin is an effective anti-cancer agent against breast cancer, lung cancer, and prostate cancer. In the crystal structure (PDB ID: 5G5J), it was found that metformin is found in the active site of CYP3A4, and the associated anti-cancer effect was explored.

Cystic MED15::TFE3 translocation renal cell carcinoma: histologic mimicker of multilocular cystic renal neoplasm of low malignant potential with review of the literature.

Presented are four cystic renal masses which harbored a MED15::TFE3 gene fusion detected by RNAseq, mimicking multilocular cystic neoplasm of low malignant potential. Clinicopathologic and outcomes data were collected for all cases. Radiologically, three cases were diagnosed as complex cystic masses and one case as a renal cyst, three years prior to surgery.

Endometrial Carcinomas With Subclonal Loss of Mismatch Repair Proteins: A Clinicopathologic and Genomic Study.

Subclonal loss of mismatch repair (MMR) proteins has been described in a small subset of endometrial carcinomas (ECs), but the genomic basis for this phenomenon has received limited attention. Herein, we retrospectively evaluated all ECs with MMR immunohistochemistry (n=285) for subclonal loss, and in those (n=6), performed a detailed clinicopathologic and genomic comparison of the MMR-deficient and MMR-proficient components. Three tumors were FIGO stage IA, and one each stage IB, II, and IIIC2.

Inactivation Predicts Rapid Recurrence in Inoperable Early-Stage Non-Small-Cell Lung Cancer.

Purpose: Molecular factors predicting relapse in early-stage non-small-cell lung cancer (ES-NSCLC) are poorly understood, especially in inoperable patients receiving radiotherapy (RT). In this study, we compared the genomic profiles of inoperable and operable ES-NSCLC.

Materials And Methods: This retrospective study included 53 patients with nonsquamous ES-NSCLC (stage I-II) treated at a single institution (University of Chicago) with surgery (ie, operable; n = 30) or RT (ie, inoperable; n = 23) who underwent tumor genomic profiling.

TSC/MTOR mutated renal cell carcinoma with leiomyomatous stroma is a distinct entity: a comprehensive study of 12 cases.

The 2016 World Health Organization (WHO) Classification of Tumors of the Urinary System includes renal cell carcinoma (RCC) with leiomyomatous stroma (RCC-LS) as a provisional category. Recent studies have shown that this category includes at least 4 subtypes: clear cell (CCRCC), clear cell papillary renal cell tumor (CCPRCT), ELOC (TCEB1) mutated, and a subtype of RCC with TSC/MTOR mutations. The most recent 2022 World Health Organization (WHO) Classification of Tumors of the Urinary System includes ELOC mutated RCC-LS as a distinct entity but does not address any other renal tumors with smooth muscle stroma.

Feasibility and limitations of cultured skin fibroblasts for germline genetic testing in hematologic disorders.

To avoid acquired variants found in the blood, cultured skin fibroblasts are a recommended DNA source for germline genetic testing in patients with hematologic disorders, but data are lacking regarding practicality and limitations. We conducted a retrospective cohort study of 350 subjects with hematologic disorders who underwent skin fibroblast culture for germline genetic testing. We analyzed next-generation sequencing data from the targeted capture of 144 inherited cancer and bonemarrow failure genes to identify variants at heterozygous and subclonal variant allele frequencies.

Recurrent Loss of Heterozygosity in Pancreatic Neuroendocrine Tumors.

Chromosomal aneuploidies are prognostic markers across a wide variety of tumor types, and recent literature suggests that pancreatic neuroendocrine tumors are no different. In this study 214 patients with grade 1, 2, or 3 pancreatic neuroendocrine tumors had their tissue examined for chromosomal copy number alterations using next-generation sequencing. Univariate and multivariate statistical analyses were performed with all-cause mortality and disease-specific mortality as the end comparators.

NF2-mutated Renal Carcinomas Have Common Morphologic Features Which Overlap With Biphasic Hyalinizing Psammomatous Renal Cell Carcinoma: A Comprehensive Study of 14 Cases.

Genetic alterations involving NF2 occur at low frequencies in renal cell carcinoma across all of the major histologic subtypes and have been associated with adverse outcomes. To better characterize tumors harboring these alterations, we identified 14 cases with NF2 mutations that had been previously diagnosed as papillary renal cell carcinoma; renal cell carcinoma, unclassified; or translocation associated renal cell carcinoma. These tumors were characterized by a tubulopapillary architecture, sclerotic stroma, microscopic coagulative necrosis, and psammomatous calcifications.

CDKN2A loss-of-function predicts immunotherapy resistance in non-small cell lung cancer.

Immune checkpoint blockade (ICB) improves outcomes in non-small cell lung cancer (NSCLC) though most patients progress. There are limited data regarding molecular predictors of progression. In particular, there is controversy regarding the role of CDKN2A loss-of-function (LOF) in ICB resistance.

Uterine inflammatory myofibroblastic tumor: First report of a ROS1 fusion.

Inflammatory myofibroblastic tumor (IMT) of the uterus is an uncommon mesenchymal neoplasm that frequently harbors ALK rearrangements. In this report, we describe the first uterine IMT with a FN1-ROS1 fusion, which occurred in a 43-year-old woman who presented with menorrhagia. Morphologically, the well-circumscribed 3 cm tumor was comprised of compact and myxoid foci of relatively bland spindle cells admixed with scattered chronic inflammatory cells limited to the myxoid areas.

Uterine PEComas: correlation between melanocytic marker expression and TSC alterations/TFE3 fusions.

Uterine PEComas often present a diagnostic challenge as they share morphological and immunohistochemical features with smooth muscle tumors. Herein we evaluated a series of 19 uterine PEComas to compare the degree of melanocytic marker expression with their molecular profile. Patients ranged from 32-77 (median 48) years, with six tumors classified as malignant based on the modified gynecologic-specific prognostic algorithm.

EWSR1-PATZ1 fusion renal cell carcinoma: a recurrent gene fusion characterizing thyroid-like follicular renal cell carcinoma.

Thyroid-like follicular renal cell carcinoma is an uncommon kidney tumor with no distinct molecular alteration described to date. This cohort of eight women with mean and median ages of 45 and 46 years, respectively (range 19-65 years), had unencapsulated, well-circumscribed tumors composed of tightly packed anastomosing follicle-like cysts filled with eosinophilic colloid-like material and lined by cuboidal cells with high nuclear to cytoplasmic ratios, oval to elongated nuclei with perpendicular arrangement toward the lumens, and prominent nuclear overlapping. The stroma between these was minimal with the exception of two tumors.

Embryonal rhabdomyosarcoma of the uterine corpus: a clinicopathological and molecular analysis of 21 cases highlighting a frequent association with DICER1 mutations.

Herein we evaluated a series of 21 embryonal rhabdomyosarcomas of the uterine corpus (ucERMS), a rare neoplasm, to characterize their morphology, genomics, and behavior. Patients ranged from 27 to 73 (median 52) years and tumors from 4 to 15 (median 9) cm, with extrauterine disease noted in two. Follow-up (median 16 months) was available for 14/21 patients; nine were alive and well, four died of disease, and one died from other causes.

Biguanides: Species with versatile therapeutic applications.

Biguanides are compounds in which two guanidine moieties are fused to form a highly conjugated system. Biguanides are highly basic and hence they are available as salts mostly hydrochloride salts, these cationic species have been found to exhibit many therapeutic properties. This review covers the research and development carried out on biguanides and accounts the various therapeutic applications of drugs containing biguanide group-such as antimalarial, antidiabetic, antiviral, anticancer, antibacterial, antifungal, anti-tubercular, antifilarial, anti-HIV, as well as other biological activities.