Revisiting the GBB reaction and redefining its relevance in medicinal chemistry: A review.

Multicomponent reactions (MCRs) have significant relevance in the field of synthetic chemistry, and in recent times one of the MCR variants, named the Groebke-Blackburn-Bienaymé (GBB) reaction, has attracted massive attention for the synthesis of biologically important scaffolds. The present review elaborates on the chemical advancement reported for the GBB reaction with an emphasis on the role of various catalytic systems. Further, the role of the GBB reaction has been redefined as a standard protocol for the synthesis of an array of potential bioactive compounds.

Clinical Outcome and Morphology-Based Analysis of p53 Aberrant and Mismatch Repair Protein-Deficient Ovarian Clear Cell Carcinoma and Their Association With p16, HER2, and PD-L1 Expression.

Objectives: We studied the prevalence and prognostic significance of mismatch repair deficient (MMRD) and p53 aberrant ovarian clear cell carcinoma (CCO) and their association with other prognostic and theranostic biomarkers (p16, HER2, PD-L1). We also aimed to identify morphologic features to serve as screening tools for immunohistochemical testing for these biomarkers.

Methods: Tissue microarrays with 3-mm cores from 71 pure CCOs were immunostained with PMS2, MSH6, p53, p16, HER2, and PD-L1.

Polysaccharides and lipoproteins as reactants for the synthesis of pharmaceutically important scaffolds: A review.

The growing number of diseases in the past decade has once again highlighted the need for extensive research on the development of novel drugs. There has been a major expansion in the number of people suffering from malignant diseases and types of life-threatening microbial infections. The high mortality rates caused by such infections, their associated toxicity, and a growing number of microbes with acquired resistance necessitate the need to further explore and develop the synthesis of pharmaceutically important scaffolds.

Ovarian Clear Cell Carcinoma and Markers of Epithelial-Mesenchymal Transition (EMT): Immunohistochemical Characterization of Tumor Budding.

Tumor budding, largely considered a manifestation of epithelial-mesenchymal transition (EMT) is an established prognostic marker for several cancers. In a recent study, tumor budding was associated with poor clinical outcomes in early-stage ovarian clear cell carcinoma. Here, we evaluated the immune expression of 3 proteins shown to be associated with EMT (E-cadherin, β-catenin, and glypican-3) in 72 primary tumors of ovarian clear cell carcinoma with median follow-up of 39.

Programmed Death Ligand 1 (PD-L1) Expression and CD8 + Tumor-infiltrating Lymphocyte-based Tumor Immune Microenvironment Classification in Gynecologic Carcinosarcoma: Prognostic Impact and Implications for Therapy.

To investigate the prevalence and prognostic significance of programmed death ligand-1 (PD-L1) expression and CD8 + tumor-infiltrating lymphocytes (TILs) in gynecologic carcinosarcoma, 81 cases (68 uterine, 12 ovarian, and 1 fallopian tube) were immunostained with PD-L1 and CD8 using tissue microarrays (3 mm core diameter) from intratumoral areas with the highest TILs. Tumor proportion score (TPS) ≥1% and combined positive score (CPS) ≥1 were considered positive for PD-L1. CD8 + TILs were counted in each core, and CD8 + TIL density (CD8TILD) was calculated.

Integrated Analysis of Ovarian Juvenile Granulosa Cell Tumors Reveals Distinct Epigenetic Signatures and Recurrent TERT Rearrangements.

Purpose: Adult granulosa cell tumor (AGCT) is characterized by the somatic FOXL2 p.C134W mutation, and recurrences have been associated with TERT promoter and KMT2D-truncating mutations. Conversely, the molecular underpinnings of the rare juvenile granulosa cell tumor (JGCT) have not been well elucidated.

Exploration of novel TOSMIC tethered imidazo[1,2-a]pyridine compounds for the development of potential antifungal drug candidate.

New candidates of imidazo[1,2-a]pyridine were designed by combining 2-amino pyridine, TOSMIC and various assorted aldehydes to explore their antioxidant and antifungal potential. The design of these derivatives was based on utilizing the antifungal potential of azoles and TOSMIC moiety. These derivatives were synthesized by adopting multi-component reaction methodology, as it serves as a rapid and efficient tool to target structurally diverse heterocyclic compounds in quantitative yield.

Intratumoral budding is associated with poor clinical outcome in early-stage clear cell carcinoma of ovary.

Aims: Clear cell carcinoma of ovary (CCC) is considered a high-grade malignancy by default and the role of histological grading for assessing clinical outcome is not established. We aimed to evaluate histopathological features associated with clinical outcome in CCC patients.

Methods And Results: Seventy-six cases of CCC with available clinical follow-up information were studied.

Amplification of MDM2 and Loss of p16 Expression: Do They Have a Role in Malignant Transformation of Ovarian Brenner Tumor?

Objectives: To review the significance of MDM2 and cyclin D1 expression and loss of p16 expression in malignant and borderline Brenner tumors (BTs) of the ovary.

Methods: We describe 2 new cases of ovarian BT, 1 malignant and 1 borderline. We studied MDM2, p16, and cyclin D1 expression by immunohistochemistry in the benign, borderline, and malignant components of these 2 cases and in 5 additional cases of benign BT.

Novel nucleosides as potential inhibitors of fungal lanosterol 14α-demethylase: an and study.

The global burden of fungal infections has transitioned from a case-specific observation to a major cause of high human mortality. Therefore, novel compounds with innovative methodologies need to be synthesized and evaluated for their antifungal potential to keep pace with the current clinical demands. An efficient synthetic pathway was developed for the synthesis of 21 synthetic novel nucleosides.

Inflammatory Myofibroblastic Tumor in Female Genital Tract.

Context.—: Inflammatory myofibroblastic tumor is a mesenchymal neoplasm of low malignant potential. It was first described in lung, but is known to occur in many extrapulmonary sites including female genital organs, most commonly the uterus.

Hormonal and Growth Regulation of Epithelial and Stromal Cells From the Normal and Malignant Endometrium by Pigment Epithelium-Derived Factor.

We discovered that pigment epithelium-derived factor (PEDF)-null mice have endometrial hyperplasia, the precursor to human type I endometrial cancer (ECA), which is etiologically linked to unopposed estrogen (E2), suggesting that this potent antiangiogenic factor might contribute to dysregulated growth and the development of type I ECA. Treatment of both ECA cell lines and primary ECA cells with recombinant PEDF dose dependently decreased cellular proliferation via an autocrine mechanism by blocking cells in G1 and G2 phases of the cell cycle. Consistent with the known opposing effects of E2 and progesterone (Pg) on endometrial proliferation, Pg increases PEDF protein synthesis and release, whereas E2 has the converse effect.

Marjolin's Ulcer of the Pleural Surface Within a Long-Standing Eloesser Flap.

Marjolin's ulcers typically result from long-term chronic inflammation of a squamous surface, most often related to burns and other scars. This report describes a squamous cell carcinoma arising from the pleural surface in a patient with a chronically neglected Eloesser flap.

TGF-β activates APC through Cdh1 binding for Cks1 and Skp2 proteasomal destruction stabilizing p27kip1 for normal endometrial growth.

We previously reported that aberrant TGF-β/Smad2/3 signaling in endometrial cancer (ECA) leads to continuous ubiquitylation of p27(kip1)(p27) by the E3 ligase SCF-Skp2/Cks1 causing its degradation, as a putative mechanism involved in the pathogenesis of this cancer. In contrast, normal intact TGF-β signaling prevents degradation of nuclear p27 by SCF-Skp2/Cks1 thereby accumulating p27 to block Cdk2 for growth arrest. Here we show that in ECA cell lines and normal primary endometrial epithelial cells, TGF-β increases Cdh1 and its binding to APC/C to form the E3 ligase complex that ubiquitylates Cks1 and Skp2 prompting their proteasomal degradation and thus, leaving p27 intact.

Pelvic Ependymoma With Clinical Response to GnRH Analog Therapy: A Case Report With an Overview of Primary Extraneural Ependymomas.

Extraneural ependymomas are rare tumors that occur in sacrococcygeal, pelvic and extra pelvic regions. While sacrococcygeal extraneural ependymomas are equally distributed among males and females, pelvic and extra pelvic ependymomas have been exclusively reported in women, mainly of child bearing age. We present a case of extraneural, pelvic ependymoma that showed clinical response to GnRH therapy with its immunohistochemical and electron microscopic analysis, and an overview of primary extraneural ependymomas based on a review of all such cases published in English literature.

Juxta-adrenal Ancient Schwannoma: A Rare Retroperitoneal Tumor.

Retroperitoneal schwannoma is a rare tumor that is often misdiagnosed as malignancy due to a concerning appearance on cross-sectional imaging. Pathology and immunohistochemistry form the gold standard for diagnosis; as such, local excision is the treatment of choice for this disease. We present two cases of juxta-adrenal ancient schwannoma that were treated with adrenalectomy and discuss the current literature regarding this entity.

Retropharyngeal ganglioneuroma: a case report.

Ganglioneuromas are uncommon, benign, and highly differentiated tumors arising from sympathetic ganglia. Common sites for these tumors include the paraspinal region of the retroperitoneum and posterior mediastinum. We report a case of a retropharyngeal ganglioneuroma, a rare occurrence, emphasizing its key imaging characteristics.

Fascin expression in serous tumors of ovary correlates with aggressiveness of malignancy.

Ovarian serous tumors make up about one-fourth of all ovarian tumors. There is a spectrum of proliferation and cellular atypia in these tumors with benign serous cystadenoma, borderline tumors, and low grade or type I serous carcinoma at the lower end and type II or high-grade serous papillary cystadenocarcinoma at the higher end. Fascin is a globular actin cross-linking protein involved in cell motility that has been shown to be upregulated in many human neoplasms and associated with the aggressiveness of malignancy.

Utility of p16INK4a, CEA, Ki67, P53 and ER/PR in the differential diagnosis of benign, premalignant, and malignant glandular lesions of the uterine cervix and their relationship with Silverberg scoring system for endocervical glandular lesions.

Early detection of premalignant and malignant glandular lesions of the uterine cervix and their distinction from benign mimics is crucial but sometimes difficult. In this study, we investigated utility of expression of p16, CEA, Ki67, p53 and ER/PR in evaluating the benign, premalignant, and malignant glandular lesions of the uterine cervix. A total of 35 cervical cone or LEEP cases were collected including 14 adenocarcinoma in situ (AIS), 7 endocervical glandular dysplasia (EGD), and 14 benign mimics (BM).