PAF1/HIF1α axis rewires the glycolytic metabolism to fuel aggressiveness of pancreatic cancer.

Background: PAF1/PD2 deregulation contributes to tumorigenesis, drug resistance, and cancer stem cell maintenance in Pancreatic Cancer (PC). Recent studies demonstrate that metabolic reprogramming plays a role in PC progression, but the mechanism is poorly understood. Here, we focused on examining the role of PAF1/PD2 in the metabolic rewiring of PC.

Chimeric antibody targeting unique epitope on onco-mucin16 reduces tumor burden in pancreatic and lung malignancies.

Aberrantly expressed onco-mucin 16 (MUC16) and its post-cleavage generated surface tethered carboxy-terminal (MUC16-Cter) domain are strongly associated with poor prognosis and lethality of pancreatic (PC) and non-small cell lung cancer (NSCLC). To date, most anti-MUC16 antibodies are directed towards the extracellular domain of MUC16 (CA125), which is usually cleaved and shed in the circulation hence obscuring antibody accessibility to the cancer cells. Herein, we establish the utility of targeting a post-cleavage generated, surface-tethered oncogenic MUC16 carboxy-terminal (MUC16-Cter) domain by using a novel chimeric antibody in human IgG1 format, ch5E6, whose epitope expression directly correlates with disease severity in both cancers.

MUC16 promotes triple-negative breast cancer lung metastasis by modulating RNA-binding protein ELAVL1/HUR.

Background: Triple-negative breast cancer (TNBC) is highly aggressive with an increased metastatic incidence compared to other breast cancer subtypes. However, due to the absence of clinically reliable biomarkers and targeted therapy in TNBC, outcomes are suboptimal. Hence, there is an urgent need to understand biological mechanisms that lead to identifying novel therapeutic targets for managing metastatic TNBC.

Identification of lipid regulatory genes modulated by polyherbal formulation in chicken liver tissues using transcriptome analysis.

Objective: To elucidate the cellular mechanisms of polyherbal formulation [Kolin Plus (KP)], genomics was performed to delineate the genes and pathways associated with lipid regulation through transcriptional profiling of the liver in commercial broilers raised on diets deficient in choline chloride (CCL).

Materials And Methods: The gene expression patterns were studied for four groups [normal diet: normal, choline chloride deficient (CCD), KP (400 gm/ton), and CCL (400 gm/ton)] using Agilent microarray on day 42. The hierarchical cluster analysis was carried out on 12,614 differentially expressed genes (DEGs) with a similar expression.

Small molecule inhibitor against onco-mucins disrupts Src/FosL1 axis to enhance gemcitabine efficacy in pancreatic ductal adenocarcinoma.

Mucin MUC4 is an aberrantly expressed oncogene in pancreatic ductal adenocarcinoma (PDAC), yet no pharmacological inhibitors have been identified to target MUC4. Here, we adapted an in silico screening method using the Cancer Therapeutic Response Database (CTRD) to Identify Small Molecule Inhibitors against Mucins (SMIMs). We identified Bosutinib as a candidate drug to target oncogenic mucins among 126 FDA-approved drugs from CTRD screening.

Muc16 depletion diminishes KRAS-induced tumorigenesis and metastasis by altering tumor microenvironment factors in pancreatic ductal adenocarcinoma.

MUC16, membrane-bound mucin, plays an oncogenic role in pancreatic ductal adenocarcinoma (PDAC). However, the pathological role of MUC16 in the PDAC progression, tumor microenvironment, and metastasis in cooperation with Kras and Trp53 mutations remains unknown. Deletion of Muc16 with activating mutations Kras and Trp53 in mice significantly decreased progression and prolonged overall survival in Kras; Trp53; Pdx-1-Cre; Muc16 (KPCM) and Kras; Pdx-1-Cre; Muc16 (KCM), as compared to Kras; Trp53; Pdx-1-Cre (KPC) and Kras; Pdx-1-Cre (KC) mice, respectively.

MUC16 Promotes Liver Metastasis of Pancreatic Ductal Adenocarcinoma by Upregulating NRP2-Associated Cell Adhesion.

Unlabelled: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer, as it commonly metastasizes to the liver resulting in an overall poor prognosis. However, the molecular mechanism involved in liver metastasis remains poorly understood. Here, we aimed to identify the MUC16-mediated molecular mechanism of PDAC-liver metastasis.

PGC1α-Mediated Metabolic Reprogramming Drives the Stemness of Pancreatic Precursor Lesions.

Purpose: Metabolic reprogramming and cancer stem cells drive the aggressiveness of pancreatic ductal adenocarcinoma (PDAC). However, the metabolic and stemness programs of pancreatic precursor lesions (PPL), considered early PDAC development events, have not been thoroughly explored.

Experimental Design: Meta-analyses using gene expression profile data from NCBI Gene Expression Omnibus and IHC on tissue microarrays (TMA) were performed.

Mucins reprogram stemness, metabolism and promote chemoresistance during cancer progression.

Mucins are high-molecular-weight glycoproteins dysregulated in aggressive cancers. The role of mucins in disease progression, tumor proliferation, and chemotherapy resistance has been studied extensively. This article provides a comprehensive review of mucin's function as a physical barrier and the implication of mucin overexpression in impeded drug delivery to solid tumors.

ST6GalNAc-I promotes lung cancer metastasis by altering MUC5AC sialylation.

Lung cancer (LC) is the leading cause of cancer-related mortality. However, the molecular mechanisms associated with the development of metastasis are poorly understood. Understanding the biology of LC metastasis is critical to unveil the molecular mechanisms for designing targeted therapies.

Metabolic programming of distinct cancer stem cells promotes metastasis of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) metastasizes to distant organs, which is the primary cause of mortality; however, specific features mediating organ-specific metastasis remain unexplored. Emerging evidence demonstrates that cancer stem cells (CSCs) and cellular metabolism play a pivotal role in metastasis. Here we investigated the role of distinct subtypes of pancreatic CSCs and their metabolomic signatures in organ-specific metastatic colonization.

Unraveling mucin domains in cancer and metastasis: when protectors become predators.

A dynamic mucosal layer shields the epithelial cells lining the body cavities and is made up of high molecular weight, heavily glycosylated, multidomain proteins called mucins. Mucins, broadly grouped into transmembrane and secreted mucins, are the first responders to any mechanical or chemical insult to the epithelia and help maintain tissue homeostasis. However, their intrinsic properties to protect and repair the epithelia are exploited during oncogenic processes, where mucins are metamorphosed to aid the tumor cells in their malignant journey.

Effect of dietary supplementation of phytogenic feed additive on performance traits, serum neopterin, and cutaneous basophil hypersensitivity response in heat-induced stress model of broiler chickens.

Objective: The trial was aimed at assessing the effect of phytogenic feed additive (PFA), a natural adaptogen, on growth performance, serum neopterin level, and cutaneous basophil hypersensitivity (CBH) response in heat-induced stress model of broilers.

Materials And Methods: One-day-old Ross 308 chicks ( = 360) were randomly distributed among normal control (NOR), heat-stress control (HSC), and PFA treatment (HSC plus PFA at 200 gm/ton of feed) group. HSC and PFA groups were subjected to heat stress (HS) (32°C-36°C) from 9:00 a.

Evaluation of a polyherbal formulation for the management of wet litter in broiler chickens: Implications on performance parameters, cecal moisture level, and footpad lesions.

Objective: The study was carried out to develop a wet litter model with magnesium chloride to assess the effectiveness of a polyherbal formulation (PHF) on growth performance, litter and cecal moisture (LCM) level, cecal consistency (CC) score, and footpad lesions (FPLs) score in Ross 308 broiler chickens.

Materials And Methods: 1,200 one-day-old chicks were assigned into five groups: normal control, negative control [NTC; treated with 1.7% magnesium chloride hexahydrate (MgCl.

Evaluation of polyherbal formulation and synthetic choline chloride on choline deficiency model in broilers: implications on zootechnical parameters, serum biochemistry and liver histopathology.

Objective: The study was designed to establish choline deficiency model (CDM) in broilers for evaluating efficacy of polyherbal formulation (PHF) in comparison with synthetic choline chloride (SCC).

Methods: A total of 2,550 one-day-old Cobb 430 broiler chicks were randomly assigned to different groups in three experiments. In experiment 1, G1 and G2 served as normal controls and were fed a basal diet with 100% soybean meal (SBM) as a major protein source supplemented with and without SCC, respectively.

Alleviation of Heat Stress by a Polyherbal Formulation, Phytocee™: Impact on Zootechnical Parameters, Cloacal Temperature, and Stress Markers.

Background: The range of thermoneutral zone of chickens is narrow, and they become easily susceptible to environmental stress, a common and major concern for poultry causing a production loss.

Objective: The present study was designed to comparatively evaluate anti-stress activity of Phytocee™ and Vitamin C in chickens reared under heat stress.

Materials And Methods: A total of 600-day-old chicks of Cobb 400 were randomly assigned to 4 groups with 6 replicates comprising 25 birds each ( = 150).

Giant obscurins regulate the PI3K cascade in breast epithelial cells via direct binding to the PI3K/p85 regulatory subunit.

Obscurins are a family of giant cytoskeletal proteins, originally identified in striated muscles where they have structural and regulatory roles. We recently showed that obscurins are abundantly expressed in normal breast epithelial cells where they play tumor and metastasis suppressing roles, but are nearly lost from advanced stage breast cancer biopsies. Consistent with this, loss of giant obscurins from breast epithelial cells results in enhanced survival and growth, epithelial to mesenchymal transition (EMT), and increased cell migration and invasion in vitro and in vivo.

Exploiting Nanotechnology for the Development of MicroRNA-Based Cancer Therapeutics.

MicroRNAs (miRNAs/miRs) represent a novel class of small non-coding RNAs that post-transcriptionally regulate gene expression by base pairing with complementary sequences in the 3' untranslated region (UTR) of target mRNAs. Functional studies suggest that miRNAs control almost every biological process, and their aberrant expression leads to a disease state, such as cancer. Differential expression of miRNAs in cancerous versus normal cells have generated enormous interest for the development of miRNA-based cancer cell-targeted therapeutics.

p-21 activated kinase 4 (PAK4) maintains stem cell-like phenotypes in pancreatic cancer cells through activation of STAT3 signaling.

Pancreatic cancer (PC) remains a highly lethal malignancy due to its unusual chemoresistance and high aggressiveness. A subpopulation of pancreatic tumor cells, known as cancer stem cells (CSCs), is considered responsible not only for tumor-maintenance, but also for its widespread metastasis and therapeutic failure. Here we investigated the role of p-21 activated kinase 4 (PAK4) in driving PC stemness properties.

Development and Characterization of a Novel in vitro Progression Model for UVB-Induced Skin Carcinogenesis.

Epidemiological studies suggest ultraviolet B (UVB) component (290-320 nm) of sun light is the most prevalent etiologic factor for skin carcinogenesis--a disease accounting for more than two million new cases each year in the USA alone. Development of UVB-induced skin carcinoma is a multistep and complex process. The molecular events that occur during UVB-induced skin carcinogenesis are poorly understood largely due to the lack of an appropriate cellular model system.

Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation.

African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood.

Colocalization of β-catenin with Notch intracellular domain in colon cancer: a possible role of Notch1 signaling in activation of CyclinD1-mediated cell proliferation.

The Wnt and Notch1 signaling pathways play major roles in intestinal development and tumorigenesis. Sub-cellular localization of β-catenin has been implicated in colorectal carcinogenesis. However, the β-catenin and Notch intracellular domain (NICD) interaction has to be addressed.

Distribution and homing pattern of c-kit+ Sca-1+ CXCR4+ resident cardiac stem cells in neonatal, postnatal, and adult mouse heart.

Introduction: The origin of heart-forming cells and their roles in organ development have fascinated biologists for over a century. C-X-C chemokine receptor type 4 plays a crucial role during embryonic development and in maintaining the stem cell niche and homing. The aim of the present was to study the expression pattern of resident cardiac stem cell markers and their homing factor in neonatal, postnatal, and adult mouse heart.