A Stem-like Patient-Derived Ovarian Cancer Model of Platinum Resistance Reveals Dissociation of Stemness and Resistance.

To understand chemoresistance in the context of cancer stem cells (CSC), a cisplatin resistance model was developed using a high-grade serous ovarian cancer patient-derived, cisplatin-sensitive sample, PDX4. As a molecular subtype-specific stem-like cell line, PDX4 was selected for its representative features, including its histopathological and mutation status, and exposed to cisplatin in vitro. In the cisplatin-resistant cells, transcriptomics were carried out, and cell morphology, protein expression, and functional status were characterized.

Role of epithelial-mesenchymal transition factor SNAI1 and its targets in ovarian cancer aggressiveness.

Ovarian cancer remains the most lethal gynecologic malignancy in the USA. For over twenty years, epithelial-mesenchymal transition (EMT) has been characterized extensively in development and disease. The dysregulation of this process in cancer has been identified as a mechanism by which epithelial tumors become more aggressive, allowing them to survive and invade distant tissues.

Racial and Ethnic Disparities in Gynecologic Carcinosarcoma: A Single-Institution Experience.

We aimed to determine the incidence, treatment regimen, and treatment outcomes (including progression-free survival and overall survival) of gynecologic carcinosarcoma, a rare, aggressive, and understudied gynecologic malignancy. This retrospective review included all patients with gynecologic cancers diagnosed and treated at a single tertiary care comprehensive cancer center between January 2012 and May 2021. A total of 2116 patients were eligible for review, of which 84 cases were identified as carcinosarcoma: 66 were uterine (5.

GA-OH enhances the cytotoxicity of photon and proton radiation in HPV HNSCC cells.

Introduction: Treatment-related toxicity following either chemo- or radiotherapy can create significant clinical challenges for HNSCC cancer patients, particularly those with HPV-associated oropharyngeal squamous cell carcinoma. Identifying and characterizing targeted therapy agents that enhance the efficacy of radiation is a reasonable approach for developing de-escalated radiation regimens that result in less radiation-induced sequelae. We evaluated the ability of our recently discovered, novel HPV E6 inhibitor (GA-OH) to radio-sensitize HPV+ and HPV- HNSCC cell lines to photon and proton radiation.

Genetic Testing in the Latinx community: Impact of acculturation and provider relationships.

Objectives: The current study aimed to explore attitudes toward genetic germline testing and intentions to test in Latinas from Southern California. We hypothesized that patients' acculturation and education levels, as well as comfort with health care providers, are positively associated with attitudes and intentions toward genetic testing.

Methods: A survey was offered concurrently to Latinx female patients at a gynecologic oncology practice and to unaffiliated Latinx community members.

TOP1 inhibition induces bifurcated JNK/MYC signaling that dictates cancer cell sensitivity.

Triple-negative breast cancer (TNBC) does not respond to anti-estrogen and anti-HER2 therapies and is commonly treated by chemotherapy. TNBC has a high recurrence rate, particularly within the first 3 years. Thus, there is an urgent clinical need to develop more effective therapies for TNBC.

Reduces Aggressive Phenotype and Induces in Ovarian Cancer Cells.

High-grade serous carcinoma of the ovary is a deadly gynecological cancer with poor long-term survival. Dysregulation of microRNAs has been shown to contribute to the formation of cancer stem cells (CSCs), an important part of oncogenesis and tumor progression. The family of microRNAs has previously been shown to regulate stemness and has tumor suppressive actions in a variety of cancers, including ovarian.

The Epithelial-Mesenchymal Transcription Factor Represses Transcription of the Tumor Suppressor miRNA in Cancer.

We aimed to determine the mechanism of epithelial-mesenchymal transition (EMT)-induced stemness in cancer cells. Cancer relapse and metastasis are caused by rare stem-like cells within tumors. Studies of stem cell reprogramming have linked repression and acquisition of stemness with the EMT factor, .

Germline BRCA Mutation Rates in Latina Women Presenting for Gynecologic Oncology Care.

Objective: Germline BRCA mutation rates in the Latina population are yet to be well described. We aimed to quantitate the rates of referral for genetic testing in qualifying women and testing completion rates in a population of women presenting for gynecologic oncology care. Results were then stratified by ethnic/racial background.

Current opinion, status and future development of digital pathology in Switzerland.

Aims: The transition from analogue to digital pathology (DP) is underway in Switzerland. To assess relevant experiences of pathologists with DP and gauge their outlook towards a digital future, a national survey was conducted by the Swiss Digital Pathology Consortium. Similar surveys were conducted in other countries, enabling a meta-analysis of DP experiences.

Let-7 as biomarker, prognostic indicator, and therapy for precision medicine in cancer.

Abnormal regulation and expression of microRNAs (miRNAs) has been documented in various diseases including cancer. The miRNA let-7 (MIRLET7) family controls developmental timing and differentiation. Let-7 loss contributes to carcinogenesis via an increase in its target oncogenes and stemness factors.

Putative tumor suppressor cytoglobin promotes aryl hydrocarbon receptor ligand-mediated triple negative breast cancer cell death.

Nearly 40 000 women die annually from breast cancer in the United States. Clinically available targeted breast cancer therapy is largely ineffective in triple negative breast cancer (TNBC), characterized by tumors that lack expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2). TNBC is associated with a poor prognosis.

Epithelial-mesenchymal Transition and Cancer Stem Cells: At the Crossroads of Differentiation and Dedifferentiation.

In this review, we explore the connections between epithelial-mesenchymal transition (EMT) and differentiation status. EMTs in development have been described as differentiation events, while in most cases EMTs in cancer have been depicted as dedifferentiation events. We will briefly summarize both embryo development and cancer progression with regard to the involvement of EMT and cell differentiation status.

RNA sequencing reveals upregulation of a transcriptomic program associated with stemness in metastatic prostate cancer cells selected for taxane resistance.

Patients with metastatic castration-resistant prostate cancer (mCRPC) develop resistance to conventional therapies including docetaxel (DTX). Identifying molecular pathways underlying DTX resistance is critical for developing novel combinatorial therapies to prevent or reverse this resistance. To identify transcriptomic signatures associated with acquisition of chemoresistance we profiled gene expression in DTX-sensitive and -resistant mCRPC cells using RNA sequencing (RNA-seq).

Snail knockdown reverses stemness and inhibits tumour growth in ovarian cancer.

To develop effective therapies for advanced high grade serous ovarian cancer (HGSOC), understanding mechanisms of recurrence and metastasis is necessary. In this study, we define the epithelial/mesenchymal status of cell lines that accurately model HGSOC, and evaluate the therapeutic potential of targeting Snai1 (Snail), a master regulator of the epithelial/mesenchymal transition (EMT) in vitro and in vivo. The ratio of Snail to E-cadherin (S/E index) at RNA and protein levels was correlated with mesenchymal morphology in four cell lines.

Hyaluronic acid conjugated nanoparticle delivery of siRNA against TWIST reduces tumor burden and enhances sensitivity to cisplatin in ovarian cancer.

TWIST protein is critical to development and is activated in many cancers. TWIST regulates epithelial-mesenchymal transition, and is linked to angiogenesis, metastasis, cancer stem cell phenotype, and drug resistance. The majority of epithelial ovarian cancer (EOC) patients with metastatic disease respond well to first-line chemotherapy but most relapse with disease that is both metastatic and drug resistant, leading to a five-year survival rate under 20%.

Palmitic acid is a toll-like receptor 4 ligand that induces human dendritic cell secretion of IL-1β.

Palmitic acid (PA) and other saturated fatty acids are known to stimulate pro-inflammatory responses in human immune cells via Toll-like receptor 4 (TLR4). However, the molecular mechanism responsible for fatty acid stimulation of TLR4 remains unknown. Here, we demonstrate that PA functions as a ligand for TLR4 on human monocyte derived dendritic cells (MoDCs).

Chimeric Vaccine Stimulation of Human Dendritic Cell Indoleamine 2, 3-Dioxygenase Occurs via the Non-Canonical NF-κB Pathway.

A chimeric protein vaccine composed of the cholera toxin B subunit fused to proinsulin (CTB-INS) was shown to suppress type 1 diabetes onset in NOD mice and upregulate biosynthesis of the tryptophan catabolic enzyme indoleamine 2, 3-dioxygenase (IDO1) in human dendritic cells (DCs). Here we demonstrate siRNA inhibition of the NF-κB-inducing kinase (NIK) suppresses vaccine-induced IDO1 biosynthesis as well as IKKα phosphorylation. Chromatin immunoprecipitation (ChIP) analysis of CTB-INS inoculated DCs showed that RelB bound to NF-κB consensus sequences in the IDO1 promoter, suggesting vaccine stimulation of the non-canonical NF-κB pathway activates IDO1 expression in vivo.

A nontranscriptional role for Oct4 in the regulation of mitotic entry.

Rapid progression through the cell cycle and a very short G1 phase are defining characteristics of embryonic stem cells. This distinct cell cycle is driven by a positive feedback loop involving Rb inactivation and reduced oscillations of cyclins and cyclin-dependent kinase (Cdk) activity. In this setting, we inquired how ES cells avoid the potentially deleterious consequences of premature mitotic entry.

The epithelial-mesenchymal transition factor SNAIL paradoxically enhances reprogramming.

Reprogramming of fibroblasts to induced pluripotent stem cells (iPSCs) entails a mesenchymal to epithelial transition (MET). While attempting to dissect the mechanism of MET during reprogramming, we observed that knockdown (KD) of the epithelial-to-mesenchymal transition (EMT) factor SNAI1 (SNAIL) paradoxically reduced, while overexpression enhanced, reprogramming efficiency in human cells and in mouse cells, depending on strain. We observed nuclear localization of SNAI1 at an early stage of fibroblast reprogramming and using mouse fibroblasts expressing a knockin SNAI1-YFP reporter found cells expressing SNAI1 reprogrammed at higher efficiency.

Influence of threonine metabolism on S-adenosylmethionine and histone methylation.

Threonine is the only amino acid critically required for the pluripotency of mouse embryonic stem cells (mESCs), but the detailed mechanism remains unclear. We found that threonine and S-adenosylmethionine (SAM) metabolism are coupled in pluripotent stem cells, resulting in regulation of histone methylation. Isotope labeling of mESCs revealed that threonine provides a substantial fraction of both the cellular glycine and the acetyl-coenzyme A (CoA) needed for SAM synthesis.

Nanog-like regulates endoderm formation through the Mxtx2-Nodal pathway.

In mammalian embryonic stem cells, the acquisition of pluripotency is dependent on Nanog, but the in vivo analysis of Nanog has been hampered by its requirement for early mouse development. In an effort to examine the role of Nanog in vivo, we identified a zebrafish Nanog ortholog and found that its knockdown impaired endoderm formation. Genome-wide transcription analysis revealed that nanog-like morphants fail to develop the extraembryonic yolk syncytial layer (YSL), which produces Nodal, required for endoderm induction.