Axillary lymph node metastasis (ALNM) in triple negative breast cancer (TNBC) will lead to poor prognosis. Recent studies have shown that long non-coding RNAs (lncRNAs) were involved in the progression of tumors. This study aimed to explore the role and mechanism of lncRNA-MALAT1 in the progression of TNBC and its relationship with ALNM.
View Article and Find Full Text PDFAccessory navicular (AN) is a developmental variation of the secondary ossification center of the navicular tuberosity. Ten percent of patients with AN will have pain symptoms that affect walking and life. As the AN changes the position of the posterior tibial tendon insertion, children with AN often have posterior tibial tendon function insufficiency and flexible flat foot.
View Article and Find Full Text PDFTo identify drivers of sensitivity and resistance to Protein Arginine Methyltransferase 5 (PRMT5) inhibition, we perform a genome-wide CRISPR/Cas9 screen. We identify TP53 and RNA-binding protein MUSASHI2 (MSI2) as the top-ranked sensitizer and driver of resistance to specific PRMT5i, GSK-591, respectively. TP53 deletion and TP53 mutation are biomarkers of resistance to GSK-591.
View Article and Find Full Text PDFpeptide and its complexes have the effect of lowering uric acid (UA)-levels. To identify the effect and possible mechanisms, different concentrations of peptide and its complexes were administered to the zebrafish and mice hyperuricemia models, and the UA level was measured. Meanwhile, the hyperuricemic mice were treated orally at 0.
View Article and Find Full Text PDFSea cucumbers are one of many marine echinoderm animals that contain valuable nutrients and medicinal compounds. The bioactive substances in sea cucumbers make them have promising biological and pharmacological properties, including antioxidant, anti-bacterial, and anti-tumor effects. In this study, sea cucumber intestinal peptide (SCIP) is a small molecular oligopeptide (<1,000 Da) extracted from sea cucumber intestines hydrolyzed by alkaline protease.
View Article and Find Full Text PDFBackground: Triple-negative breast cancer (TNBC) is characterized by its aggressiveness and poor prognosis. Docetaxel is the common chemotherapeutic drug used in the treatment of TNBC. However, resistance to docetaxel has limited the effectiveness of TNBC treatment.
View Article and Find Full Text PDFB-cell lymphoma 6 (BCL6) is a zinc finger transcriptional repressor possessing a BTB-POZ (BR-C, ttk, and bab for BTB; pox virus and zinc finger for POZ) domain, which is required for homodimerization and association with corepressors. BCL6 has multiple roles in normal immunity, autoimmunity, and some types of lymphoma. Mice bearing disrupted BCL6 loci demonstrate suppressed high-affinity antibody responses to T-dependent antigens.
View Article and Find Full Text PDFThe profound efficacy of pan-BET inhibitors is well documented, but these epigenetic agents have shown pharmacology-driven toxicity in oncology clinical trials. The opportunity to identify inhibitors with an improved safety profile by selective targeting of a subset of the eight bromodomains of the BET family has triggered extensive medicinal chemistry efforts. In this article, we disclose the identification of potent and selective drug-like pan-BD2 inhibitors such as pyrazole (GSK809) and furan (GSK743) that were derived from the pyrrole fragment .
View Article and Find Full Text PDFThe aim of this study was to identify some biomarkers for predicting lymph node metastasis and prognosis of human epidermal growth factor receptor 2 (Her-2)-positive breast cancer (BC). We analyzed correlations between microRNAs (miRNAs) and the prognosis of patients with BC based on data collected from The Cancer Genome Atlas (TCGA) database. The expression levels of miR-455, miR-143, and miR-99a were measured in clinical samples of Her-2-positive BC patients with different degrees of lymph node metastasis.
View Article and Find Full Text PDFOnco Targets Ther
July 2018
Breast cancer is one of the most common malignancies for women, which accounts for 30% of all female malignancies. The formation of breast cancer stem cells (BCSCs) is attributed to the acquisition of stemness of tumor cells. With self-renewal potential, these stem cells are insensitive to either radiotherapy or chemotherapy but are significant in regulating tumor behaviors and drug resistance.
View Article and Find Full Text PDFWith abilities to renew themselves and lead to heterogeneity of tumors, cancer stem cells (CSCs) are similar to stem cells. As three leading causes of death that endanger women's health, breast cancer, ovarian cancer and cervical cancer are characterized by high degree of malignancy, metastasis and recurrence. Associated with women's fertility, these three malignancies are common and representative among females.
View Article and Find Full Text PDFEvasion of the potent tumour suppressor activity of p53 is one of the hurdles that must be overcome for cancer cells to escape normal regulation of cellular proliferation and survival. In addition to frequent loss of function mutations, p53 wild-type activity can also be suppressed post-translationally through several mechanisms, including the activity of PRMT5. Here we describe broad anti-proliferative activity of potent, selective, reversible inhibitors of protein arginine methyltransferase 5 (PRMT5) including GSK3326595 in human cancer cell lines representing both hematologic and solid malignancies.
View Article and Find Full Text PDFBET inhibitors exhibit broad activity in cancer models, making predictive biomarkers challenging to define. Here we investigate the biomarkers of activity of the clinical BET inhibitor GSK525762 (I-BET; I-BET762) across cancer cell lines and demonstrate that KRAS mutations are novel resistance biomarkers. This finding led us to combine BET with RAS pathway inhibition using MEK inhibitors to overcome resistance, which resulted in synergistic effects on growth and survival in RAS pathway mutant models as well as a subset of cell lines lacking RAS pathway mutations.
View Article and Find Full Text PDFBreast cancer is one of the malignant tumors with the highest morbidity and mortality. It is helpful to reduce the rate of tumor recurrence and metastasis by treating breast cancer with adjuvant chemotherapy, so as to increase the cure rate or survival of patients. In recent years, liposomes have been regarded as a kind of new carrier for targeted drugs.
View Article and Find Full Text PDFTracking transplanted stem cells is necessary to clarify cellular properties and improve transplantation success. In this study, we designed and synthesized melanin-based gadolinium (Gd )-chelate nanoparticles (MNP-Gd ) of ∼7 nm for stem cell tracking in vivo. MNP-Gd possesses many beneficial properties, such as its high stability and sensitivity, shorter T1 relaxation time, higher cell labeling efficiency, and lower cytotoxicity compared with commercial imaging agents.
View Article and Find Full Text PDFHuman epidermal growth factor receptor 2 (HER2/neu or HER2) has long been recognized as an attractive therapeutic target for breast cancer. The YVMA in-frame insertion at the residue G776 (G776(YVMA)) of HER2 kinase domain is a frequently observed mutation that can largely shift drug sensitivity in targeted therapy of HER2-positive breast cancer. Here, the molecular mechanism and biological significance of tyrosine kinase inhibitor (TKI) response to HER2 G776(YVMA) insertion were investigated in detail.
View Article and Find Full Text PDFObjective: To evaluate efficacies of three commonly used oral drugs including Berbamine Hydrochloride Tablet (B), Qijiao Shengbai Capsule (Q), and Leucogen Tablet (L) (by single drug, two drugs or three drugs) combined with granulocyte colony-stimulating factor (G-CSF) for treat ment of chemotherapy related leukocytopenia in mice.
Methods: Totally 156 Kunming male mice were divided into the normal control group (A, n=24), the model group (B, n=24), the G-CSF group (C, n =24), the G-CSF+Q group (D, n=12), G-CSF+ B (E, n=12), the G-CSF+L group (F, n=12), the G-CSF + Q + B group (G, n=12), the G-CSF + Q + L group (H, n=12), the G-CSF + L + B group (I, n=12), and the G-CSF + L + Q + B (J, n=12). Mouse models of chemotherapy related leukocytopenia were established by intraperitoneal injection of cyclophosphamide (CTX).
Objective: To investigate the protective effects and mechanisms of Radix Astragali Injection on multiple organs of rats with obstructive jaundice (OJ).
Methods: A total of 180 rats were randomly divided into the sham-operated, model control and treated groups (60 in each group). On 7, 14, 21 and 28 days after operation, the serum contents of alanine aminotransferase (ALT), aspartate aminotransferase (AST), r-glutamyl transpeptidase (r-GT), total bilirubin (TBil), direct bilirubin (DBil), blood urine nitrogen (BUN), and creatinine (CREA) were determined.
Obstructive jaundice (OJ) is classified as extrahepatic OJ or intrahepatic OJ. Extrahepatic OJ is attributed to a variety of intricate etiological factors. Research has begun with Chinese medicine (CM), which can be used as an adjunctive therapy for extrahepatic OJ.
View Article and Find Full Text PDFEthnopharmacological Relevance: The deer velvet antler is well known for its traditional medicinal value, and is widely used in the clinic. It is recorded in the Compendium of Materia Medica that the deer velvet antler replenishes vital essence and strengthens the bone.
Aim Of The Study: The goal of this study was to investigate the anti-osteoporotic effect of total velvet antler polypeptides from Cervus elaphus Linnaeus (TVAPL) on ovariectomized rats (OVX), and their possible mechanism of the action.
Background: Severe acute pancreatitis (SAP) is characterized by fatal pathogenic conditions and a high mortality. It is important to study SAP complicated with multiple organ injury. In this study we compared the protective effects of three traditional Chinese medicines (Ligustrazine, Kakonein and Panax Notoginsenoside) on the small intestine and immune organs (thymus, spleen and lymph nodes) of rats with SAP and explored their mechanism of action.
View Article and Find Full Text PDFBackground: Intestinal mucosa injury in cases of severe acute pancreatitis (SAP) or obstructive jaundice (OJ) is one of the main reasons for the accelerated aggravation of these diseases. Besides being an organ to digest and absorb nutrients, the intestine is also a unique immune organ. When SAP and OJ develop, the destruction of the intestinal mucosa barrier is an important contributing factor for the development of bacterial translocation, systemic inflammatory response syndrome, and multiple organ dysfunction syndrome.
View Article and Find Full Text PDFHepatobiliary Pancreat Dis Int
February 2010
Background: Severe acute pancreatitis (SAP) is a commonly seen acute abdominal syndrome characterized by sudden onset, rapid progression and high mortality rate. The damage in peripheral organs may be more severe than that in the pancreas, and can even lead to multiple organ dysfunction. It is critical to recognize early pathological changes in multiple organs.
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