323 results match your criteria: "and University of Pittsburgh Cancer Institute[Affiliation]"

Migfilin promotes autophagic flux through direct interaction with SNAP29 and Vamp8.

J Cell Biol

November 2024

Department of System Biology, School of Life Sciences, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, Shenzhen, China.

Autophagy plays a crucial role in cancer cell survival by facilitating the elimination of detrimental cellular components and the recycling of nutrients. Understanding the molecular regulation of autophagy is critical for developing interventional approaches for cancer therapy. In this study, we report that migfilin, a focal adhesion protein, plays a novel role in promoting autophagy by increasing autophagosome-lysosome fusion.

View Article and Find Full Text PDF

PARVB deficiency alleviates cisplatin-induced tubular injury by inhibiting TAK1 signaling.

Cell Mol Life Sci

September 2024

Department of Systems Biology, School of Life Sciences, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, Shenzhen, 518055, China.

Cisplatin-induced renal tubular injury largely restricts the wide-spread usage of cisplatin in the treatment of malignancies. Identifying the key signaling pathways that regulate cisplatin-induced renal tubular injury is thus clinically important. PARVB, a focal adhesion protein, plays a crucial role in tumorigenesis.

View Article and Find Full Text PDF

Unlike chronological age, biological age is a strong indicator of health of an individual. However, the molecular fingerprint associated with biological age is ill-defined. To define a high-resolution signature of biological age, we analyzed metabolome, circulating senescence-associated secretome (SASP)/inflammation markers and the interaction between them, from a cohort of healthy and rapid agers.

View Article and Find Full Text PDF

Background: Multiple antigens, autoantibodies (AAb), and antigen-autoantibody (Ag-AAb) complexes were compared for their ability to complement CA125 for early detection of ovarian cancer.

Methods: Twenty six biomarkers were measured in a single panel of sera from women with early stage (I-II) ovarian cancers (n = 64), late stage (III-IV) ovarian cancers (186), benign pelvic masses (200) and from healthy controls (502), and then split randomly (50:50) into a training set to identify the most promising classifier and a validation set to compare its performance to CA125 alone.

Results: Eight biomarkers detected ≥ 8% of early stage cases at 98% specificity.

View Article and Find Full Text PDF

Kindlin-2 enhances c-Myc translation through association with DDX3X to promote pancreatic ductal adenocarcinoma progression.

Theranostics

September 2023

Department of System Biology, School of Life Sciences, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, Shenzhen, 518055, China.

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive solid tumor, with extremely low survival rates. Identifying key signaling pathways driving PDAC progression is crucial for the development of therapies to improve patient response rates. Kindlin-2, a multi-functional protein, is involved in numerous biological processes including cell proliferation, apoptosis and migration.

View Article and Find Full Text PDF

Kindlin-2 promotes Src-mediated tyrosine phosphorylation of androgen receptor and contributes to breast cancer progression.

Cell Death Dis

May 2022

Department of Biology, School of Life Sciences, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, Shenzhen, 518055, China.

Androgen receptor (AR) signaling plays important roles in breast cancer progression. We show here that Kindlin-2, a focal adhesion protein, is critically involved in the promotion of AR signaling and breast cancer progression. Kindlin-2 physically associates with AR and Src through its two neighboring domains, namely F1 and F0 domains, resulting in formation of a Kindlin-2-AR-Src supramolecular complex and consequently facilitating Src-mediated AR Tyr-534 phosphorylation and signaling.

View Article and Find Full Text PDF

Interactions between the immune system and the nervous system are crucial in maintaining homeostasis, and disturbances of these neuro-immune interactions may participate in carcinogenesis and metastasis. Nerve endings have been identified within solid tumors in humans and experimental animals. Although the involvement of the efferent sympathetic and parasympathetic innervation in carcinogenesis has been extensively investigated, the role of the afferent sensory neurons and the neuropeptides in tumor development, growth, and progression is recently appreciated.

View Article and Find Full Text PDF

Circulating Cancer Biomarkers.

Cancers (Basel)

February 2021

Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.

Cancer is among the major public health problems worldwide, representing the leading cause of morbidity and mortality in industrialized countries [...

View Article and Find Full Text PDF

Communications between actin filaments and integrin-mediated focal adhesion (FA) are crucial for cell adhesion and migration. As a core platform to organize FA proteins, the tripartite ILK/PINCH/Parvin (IPP) complex interacts with actin filaments to regulate the cytoskeleton-FA crosstalk. Rsu1, a Ras suppressor, is enriched in FA through PINCH1 and plays important roles in regulating F-actin structures.

View Article and Find Full Text PDF

Human papillomavirus (HPV)(+) and HPV(-) head and neck cancer (HNC) cells' interactions with the host immune system are poorly understood. Recently, we identified molecular and functional differences in exosomes produced by HPV(+) vs. HPV(-) cells, suggesting that genetic cargos of exosomes might identify novel biomarkers in HPV-related HNCs.

View Article and Find Full Text PDF

Background: Accumulating evidence suggests a relationship between endometrial cancer and ovarian cancer. Independent genome-wide association studies (GWAS) for endometrial cancer and ovarian cancer have identified 16 and 27 risk regions, respectively, four of which overlap between the two cancers. We aimed to identify joint endometrial and ovarian cancer risk loci by performing a meta-analysis of GWAS summary statistics from these two cancers.

View Article and Find Full Text PDF

Cancer is a complex ecosystem and should be considered in the context of its cellular and molecular microenvironment, which includes the nerves. Peripheral nerves can modulate phenotype and behavior of the malignant cells and thus affect tumor growth and metastasis. Only recently has the role of neuroimmune cross-talk surfaced as a key contributor to cancer progression.

View Article and Find Full Text PDF

PINCH-1 interacts with myoferlin to promote breast cancer progression and metastasis.

Oncogene

March 2020

Department of Biology, Guangdong Provincial Key Laboratory of Cell Microenvironment and Disease Research, Shenzhen Key Laboratory of Cell Microenvironment, Southern University of Science and Technology, Shenzhen, 518055, China.

PINCH-1 is a cytoplasmic component of the cell-extracellular matrix (ECM) adhesion machine that is frequently overexpressed in cancer. The functions and mechanism of PINCH-1 in cancer, however, remain to be determined. Here, we show that PINCH-1 interacts with myoferlin, a transmembrane protein that is critical for cancer progression.

View Article and Find Full Text PDF

Ovarian cancer is the leading cause of death among gynecologic diseases in the USA and Europe. High-grade serous carcinoma (HGSC) of the ovary, the most aggressive type of ovarian cancer, is typically diagnosed at advanced stages when the 5-year survival is dismal. Since the cure rate for stage I HGSC is high, early detection of localized initial disease may improve patient outcomes.

View Article and Find Full Text PDF
Article Synopsis
  • Women of African ancestry experience lower rates of epithelial ovarian cancer (EOC) but poorer survival outcomes compared to women of European ancestry, prompting research into genetic factors.
  • A genome-wide association study identified ten loci potentially related to EOC and high-grade serous ovarian carcinoma (HGSOC) in African ancestry women, with some variants linked to genes regulating hormones and cancer.
  • The study suggests shared genetic risk factors for EOC between different ancestries and highlights specific genetic variants that may influence ovarian cancer risk and outcomes in African ancestry women.
View Article and Find Full Text PDF

Primary ovarian mucinous tumors can be difficult to distinguish from metastatic gastrointestinal neoplasms by histology alone. The expected immunoprofile of a suspected metastatic lower gastrointestinal tumor is CK7/CK20/CDX2/PAX8. This study assesses the addition of a novel marker SATB2, to improve the diagnostic algorithm.

View Article and Find Full Text PDF

We evaluated daily setup reproducibility of deep inspiration breath hold (DIBH) using mega voltage (MV) imaging for left breast cancer radiation therapy. Analysis of 109 left breast cancer patients across UPMC Hillman Cancer Center network treated using DIBH technique with daily MV imaging was done. Patient characteristics, MV imaging procedure used and inter-fraction directional shifts were collected.

View Article and Find Full Text PDF

Mechano-regulation of proline metabolism and cancer progression by kindlin-2.

Mol Cell Oncol

April 2019

Department of Pathology, School of Medicine and University of Pittsburgh Cancer Institute, University of Pittsburgh, Pittsburgh, PA, USA.

Alterations of cell mechano-environment and metabolism are common features of malignant neoplasm. We recently showed that increased stiffness of extracellular matrix is intrinsically linked to up-regulation of proline synthesis through a mechano-responsive fermitin family homolog 2 (FERMT2, best known as kindlin-2) and pyrroline-5-carboxylate reductase 1(PYCR1) complex, which in turn promotes collagen matrix synthesis, cell proliferation, survival, and cancer progression.

View Article and Find Full Text PDF

An association between genetic variants in the vitamin D receptor (VDR) gene and epithelial ovarian cancer (EOC) was previously reported in women of African ancestry (AA). We sought to examine associations between genetic variants in VDR and additional genes from vitamin D biosynthesis and pathway targets (EGFR, UGT1A, UGT2A1/2, UGT2B, CYP3A4/5, CYP2R1, CYP27B1, CYP24A1, CYP11A1, and GC). Genotyping was performed using the custom-designed 533,631 SNP Illumina OncoArray with imputation to the 1,000 Genomes Phase 3 v5 reference set in 755 EOC cases, including 537 high-grade serous (HGSOC), and 1,235 controls.

View Article and Find Full Text PDF

Purpose: Previous epidemiologic studies have shown that smoking, obesity, and physical inactivity are associated with poor survival following a diagnosis of ovarian cancer. Yet, the combined relationship of these unfavorable lifestyle factors on ovarian cancer survival has not been sufficiently investigated.

Methods: Using data pooled from 13 studies, we examined the associations between combined exposures to smoking, overweight/obesity weight, and physical inactivity and overall survival (OS) as well as progression-free survival (PFS) among women diagnosed with invasive epithelial ovarian carcinoma (n = 7,022).

View Article and Find Full Text PDF

Identification of molecular alterations driving breast cancer progression is critical for the development of effective therapy. In this study, we show that the level of α-parvin is elevated in triple-negative breast cancer cells. The depletion of α-parvin from triple-negative breast cancer cells effectively inhibits breast cancer cell growth, migration, and invasion in vitro, and tumor progression and metastasis in vivo.

View Article and Find Full Text PDF

Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer.

N Engl J Med

February 2019

From the German Breast Group, Neu-Isenburg (G.M., S.L., H.H.F., P.W.), the Center for Hematology and Oncology Bethanien, Frankfurt (S.L.), the AGO-B and HELIOS Klinikum Berlin-Buch, Berlin (M.U.), the National Center for Tumor Diseases, Heidelberg University Hospital and German Cancer Research Center, Heidelberg (A.S.), Evangelische Kliniken Gelsenkirchen, Gelsenkirchen (H.H.F.), the Arbeitsgemeinschaft Gynäkologische Onkologie - Breast and Sana Klinikum Offenbach, Offenbach (C.J.), the Department of Gynecology and Obstetrics, University Hospital Erlangen, Comprehensive Cancer Center Erlangen-EMN, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen (P.A.F.), and Mammazentrum Hamburg am Krankenhaus Jerusalem, Hamburg (P.W.) - all in Germany; the National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan (C.-S.H.); Instituto do Câncer do Estado de São Paulo, São Paulo (M.S.M.); the National Surgical Adjuvant Breast and Bowel Project (NSABP) Foundation and Orlando Health University of Florida Health Cancer Center, Orlando (E.P.M.); the NSABP Foundation and Allegheny Health Network Cancer Institute (N.W.) and the NSABP Foundation and University of Pittsburgh Cancer Institute, School of Medicine (P.R.), Pittsburgh; Hospital Universitario La Paz-Instituto de Investigación Hospital Universitario La Paz, Madrid (A.R.); Institut Régional du Cancer de Montpellier, Université de Montpellier, INSERM Unité 1194, Montpellier, France (W.J.); the NSABP Foundation and Providence Portland Medical Center, Portland, OR (A.K.C.); the National Cancer Institute, Mexico City (C.A.-S.); the NSABP Foundation and Stanford University School of Medicine, Stanford (I.L.W.), and Genentech, South San Francisco (L.H.L., D.T., M.S., S.M.S.) - both in California; Yale University School of Medicine, Yale Cancer Center, and Smilow Cancer Hospital, New Haven, CT (M.P.D.); the Ireland Cooperative Oncology Research Group, Dublin (J.P.C.); Fudan University Shanghai Cancer Center (Z.S.) and Roche (China) Holding (H.W.), Shanghai; the Cancer Center Azienda Socio Sanitaria Territoriale Papa Giovanni XXIII, Bergamo, Italy (E.R.C.); F. Hoffmann-La Roche, Welwyn Garden City, United Kingdom (H.D.); and the NSABP Foundation and Virginia Commonwealth University Massey Cancer Center, Richmond (C.E.G.).

Background: Patients who have residual invasive breast cancer after receiving neoadjuvant chemotherapy plus human epidermal growth factor receptor 2 (HER2)-targeted therapy have a worse prognosis than those who have no residual cancer. Trastuzumab emtansine (T-DM1), an antibody-drug conjugate of trastuzumab and the cytotoxic agent emtansine (DM1), a maytansine derivative and microtubule inhibitor, provides benefit in patients with metastatic breast cancer that was previously treated with chemotherapy plus HER2-targeted therapy.

Methods: We conducted a phase 3, open-label trial involving patients with HER2-positive early breast cancer who were found to have residual invasive disease in the breast or axilla at surgery after receiving neoadjuvant therapy containing a taxane (with or without anthracycline) and trastuzumab.

View Article and Find Full Text PDF

We aimed to validate the prognostic association of p16 expression in ovarian high-grade serous carcinomas (HGSC) and to explore it in other ovarian carcinoma histotypes. p16 protein expression was assessed by clinical-grade immunohistochemistry in 6525 ovarian carcinomas including 4334 HGSC using tissue microarrays from 24 studies participating in the Ovarian Tumor Tissue Analysis consortium. p16 expression patterns were interpreted as abnormal (either overexpression referred to as block expression or absence) or normal (heterogeneous).

View Article and Find Full Text PDF

A Transcriptome-Wide Association Study Among 97,898 Women to Identify Candidate Susceptibility Genes for Epithelial Ovarian Cancer Risk.

Cancer Res

September 2018

Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee.

Large-scale genome-wide association studies (GWAS) have identified approximately 35 loci associated with epithelial ovarian cancer (EOC) risk. The majority of GWAS-identified disease susceptibility variants are located in noncoding regions, and causal genes underlying these associations remain largely unknown. Here, we performed a transcriptome-wide association study to search for novel genetic loci and plausible causal genes at known GWAS loci.

View Article and Find Full Text PDF

Variants in genes encoding small GTPases and association with epithelial ovarian cancer susceptibility.

PLoS One

December 2018

Division of Population Sciences, Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, FL, United States of America.

Article Synopsis
  • Epithelial ovarian cancer (EOC) is a major cause of cancer deaths in women, and the study explores how variations in small GTPase genes may impact EOC risk.* -
  • Researchers analyzed genetic data from over 44,000 participants to find that specific variants in genes ARHGEF10L and AKAP6 are linked to increased risk for certain types of EOC.* -
  • The findings suggest that these genetic variants might influence EOC susceptibility by affecting gene regulation, indicating a need for further studies to confirm these associations.*
View Article and Find Full Text PDF