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Adaptive drug-resistance mechanisms allow human tumors to evade treatment through selection and expansion of treatment-resistant clones. Here, studying clonal evolution of tumor cells derived from human pancreatic tumors, we demonstrate that in vitro cultures and in vivo tumors are maintained by a common set of tumorigenic cells that can be used to establish clonal replica tumors (CRTs), large cohorts of animals bearing human tumors with identical clonal composition. Using CRTs to conduct quantitative assessments of adaptive responses to therapeutics, we uncovered a multitude of functionally heterogeneous subpopulations of cells with differential degrees of drug sensitivity. High-throughput isolation and deep characterization of unique clonal lineages showed genetic and transcriptomic diversity underlying functionally diverse subpopulations. Molecular annotation of gemcitabine-naive clonal lineages with distinct responses to treatment in the context of CRTs generated signatures that can predict the response to chemotherapy, representing a potential biomarker to stratify patients with pancreatic cancer.
This article was published in the following journal.
Name: Cell reports
Pancreatic cancer is one of the most aggressive human malignancies and is associated with a dismal prognosis, which can be contributed to its atypical symptoms, metastatic propensity, and significant ...
Chemoresistance is one of the major challenges for the breast cancer treatment. Owing to its heterogeneous nature, the chemoresistance mechanisms of breast cancer are complicated, and not been fully e...
The embryonic origin of pericytes is heterogeneous, both between and within organs. While pericytes of coelomic organs were proposed to differentiate from the mesothelium, a single-layer squamous epit...
To evaluate the etiologic heterogeneity between medial and lateral tibiofemoral radiographic osteoarthritis (ROA).
Metabolic rewiring is an integral part of tumor growth. Among metabolic pathways, the Mevalonic-Acid-Pathway (MVAP) plays a key role in maintaining membrane architecture through cholesterol synthesis,...
This is a study to investigate the efficacy and safety of PDR001 in patients with advanced or metastatic non-functional neuroendocrine tumors of pancreatic, gastrointestinal (GI), or thora...
An investigation of a new catheter and pressure monitor system that may help to prevent a complication called compartment syndrome from developing in an injured leg. Compartment syndrome ...
The purpose of this study is to investigate if heterogeneity in head and neck squamous cell carcinoma as seen in functional imaging with PET/MR can be correlated to biologic heterogeneity ...
At present there is no validated prognostic tool for patients with resectable pancreatic cancer (RPC) to determine how best to tailor individual therapy. This study is to see if tumor feat...
We will investigate the feasibility of a simple outpatient one time injection regimen for the treatment of Chronic Exertional Compartment Syndrome (CECS). We think botulinum toxin injectio...
The presence of apparently similar characters for which the genetic evidence indicates that different genes or different genetic mechanisms are involved in different pedigrees. In clinical settings genetic heterogeneity refers to the presence of a variety of genetic defects which cause the same disease, often due to mutations at different loci on the same gene, a finding common to many human diseases including ALZHEIMER DISEASE; CYSTIC FIBROSIS; LIPOPROTEIN LIPASE DEFICIENCY, FAMILIAL; and POLYCYSTIC KIDNEY DISEASES. (Rieger, et al., Glossary of Genetics: Classical and Molecular, 5th ed; Segen, Dictionary of Modern Medicine, 1992)
A 36-amino acid pancreatic hormone that is secreted mainly by endocrine cells found at the periphery of the ISLETS OF LANGERHANS and adjacent to cells containing SOMATOSTATIN and GLUCAGON. Pancreatic polypeptide (PP), when administered peripherally, can suppress gastric secretion, gastric emptying, pancreatic enzyme secretion, and appetite. A lack of pancreatic polypeptide (PP) has been associated with OBESITY in rats and mice.
Extracts prepared from pancreatic tissue that may contain the pancreatic enzymes or other specific uncharacterized factors or proteins with specific activities. PANCREATIN is a specific extract containing digestive enzymes and used to treat pancreatic insufficiency.
A pancreatic trypsin inhibitor common to all mammals. It is secreted with the zymogens into the pancreatic juice. It is a protein composed of 56 amino acid residues and is different in amino acid composition and physiological activity from the Kunitz bovine pancreatic trypsin inhibitor (APROTININ).
A true cyst of the PANCREAS, distinguished from the much more common PANCREATIC PSEUDOCYST by possessing a lining of mucous EPITHELIUM. Pancreatic cysts are categorized as congenital, retention, neoplastic, parasitic, enterogenous, or dermoid. Congenital cysts occur more frequently as solitary cysts but may be multiple. Retention cysts are gross enlargements of PANCREATIC DUCTS secondary to ductal obstruction. (From Bockus Gastroenterology, 4th ed, p4145)
Pancreatitis Acute pancreatitis is inflammation of the pancreas caused by the release of activated pancreatic enzymes. Common triggers are biliary tract disease and chronic heavy alcohol intake. Diagnosis is based on clinical presentation...
Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...
The pancreas secretes a number of important hormones into the digestive tract and the blood stream. Cancers are most commonly exocrine than endocrine (neuroendocrine) tumors. Functional tumors secrete hormones; Insulinoma, Gastrinoma, Somatostatinoma, VI...