المؤلفون: Li Li, Juan-Yu Hu, Jian-Yong Xu, Hai Meng, Zhengqing Yu, Xiaodong Yin

المصدر: Yonsei Medical Journal

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Progastrin-releasing peptide, 030204 cardiovascular system & hematology, GPI-Linked Proteins, Gastroenterology, Sensitivity and Specificity, 03 medical and health sciences, 0302 clinical medicine, Carcinoembryonic antigen, Stomach Neoplasms, Internal medicine, medicine, Biomarkers, Tumor, Humans, In patient, Antigens, Tumor-Associated, Carbohydrate, Stage (cooking), Peptide expression, Tumor node metastasis, Aged, Chemotherapy, biology, Receiver operating characteristic, business.industry, gastric cancer, Cancer, General Medicine, Middle Aged, medicine.disease, Prognosis, Peptide Fragments, Recombinant Proteins, Carcinoembryonic Antigen, Oncology, ROC Curve, 030220 oncology & carcinogenesis, Case-Control Studies, biology.protein, Disease Progression, Original Article, Female, progression, business

الوصف: PURPOSE The purpose of this study was to assess the diagnostic and prognostic value of serum progastrin-releasing peptide (ProGRP) in patients with gastric cancer (GC). MATERIALS AND METHODS A total of 150 patients with GC (89 males and 61 females) were recruited, including those with stage I (n=28), stage II (n=33), stage III (n=50), and stage IV (n=39) disease; 50 healthy controls and 66 patients with benign gastric diseases were also enrolled. Levels of serum ProGRP, carcinoembryonic antigen (CEA), and carbohydrate antigen 72-4 (CA72-4) were measured in all subjects. RESULTS Serum ProGRP levels were significantly higher in GC patients than in controls (p

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::bfb50c3e5a337466e778178576a5340bTest
http://europepmc.org/articles/PMC6938777Test

المؤلفون: Bénédicte Brulin, Unmesh Jadhav, Philippe Crespy, Zeinab Homayed, Jihane Boubaker-Vitre, Fanny Grillet, J. Hazerbroucq, Frédéric Hollande, Cyril Breuker, Julie Giraud, Christine Pignodel, J-F. Bourgaux, Ramesh A. Shivdasani, Philippe Jay, Julie Pannequin, Momeneh Foroutan

المساهمون: MORNET, Dominique, Institut de Génomique Fonctionnelle (IGF), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), University of Melbourne, Dana-Farber Cancer Institute [Boston], Harvard Medical School [Boston] (HMS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)

المصدر: Translational Oncology
Translational Oncology, 2020, 14 (2), pp.101001. ⟨10.1016/j.tranon.2020.101001⟩
Translational Oncology, Vol 14, Iss 2, Pp 101001-(2021)
Translational Oncology, Elsevier, 2020, 14 (2), pp.101001. ⟨10.1016/j.tranon.2020.101001⟩

مصطلحات موضوعية: 0301 basic medicine, Cancer Research, FACS, Fluorescence-Activated Cell Sorting, [SDV]Life Sciences [q-bio], Intestinal polyp, Enteroendocrine cell, Biology, Tumor initiating cells, lcsh:RC254-282, Lgr5 (GPR49), 03 medical and health sciences, 0302 clinical medicine, Intestinal mucosa, Lgr5, leucine-rich repeat containing G protein-coupled receptor 5, Neoplastic transformation, APC, Adenomatous Polyposis Coli, Original Research, PG, progastrin, Progastrin, Intestinal stem cells, Wnt signaling pathway, LGR5, CBC, crypt base columnar cells, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Adenomas, 3. Good health, SPF, Specific Pathogen Free, [SDV] Life Sciences [q-bio], 030104 developmental biology, EGFP, Enhanced Green Fluorescence Protein, Oncology, BMI1, 030220 oncology & carcinogenesis, Cancer research, Stem cell, DAPI, 4′,6-diamidino-2-phenylindole

الوصف: Highlights • Secretion of progastrin is a signature event of early malignant transformation in the colon. • In the healthy epithelium, progastrin is produced by a subset of enteroendocrine cells expressing both Bmi1 and Prox1. • LGR5-high intestinal stem cells are a primary source of progastrin production in early mouse and human intestinal adenomas.
Progastrin is an unprocessed soluble peptide precursor with a well-described tumor-promoting role in colorectal cancer. It is expressed at small levels in the healthy intestinal mucosa, and its expression is enhanced at early stages of intestinal tumor development, with high levels of this peptide in hyperplastic intestinal polyps being associated with poor neoplasm-free survival in patients. Yet, the precise type of progastrin-producing cells in the healthy intestinal mucosa and in early adenomas remains unclear. Here, we used a combination of immunostaining, RNAscope labelling and retrospective analysis of single cell RNAseq results to demonstrate that progastrin is produced within intestinal crypts by a subset of Bmi1+/Prox1+/LGR5low endocrine cells, previously shown to act as replacement stem cells in case of mucosal injury. In contrast, our findings indicate that intestinal stem cells, specified by expression of the Wnt signaling target LGR5, become the main source of progastrin production in early mouse and human intestinal adenomas. Collectively our results suggest that the previously identified feed-forward mechanisms between progastrin and Wnt signaling is a hallmark of early neoplastic transformation in mouse and human colonic adenomas.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0edac14cd110ff4d56111788f49ee3ddTest
https://hal.science/hal-03090781Test

المؤلفون: Kazuyoshi Kajimoto, Toshiko Sakuma, Masahiro Tominaga, Hironobu Goto, Toshihiko Yoshida, Yasuhiro Fujino, Dai Otsubo, Akinobu Furutani, Hisoka Yamane, Takashi Yamagishi, Sachiko Yoshida, Masayasu Nishi, Taku Matsumoto

المصدر: International Journal of Surgery Case Reports

مصطلحات موضوعية: medicine.medical_specialty, Radiography, medicine.medical_treatment, ICG, indocyanine green, Article, WHO, World Health Organization, SUVmax, maximum standardized uptake value, Metastasis, Lesion, 03 medical and health sciences, LCNEC, large-cell neuroendocrine carcinoma, 0302 clinical medicine, Case report, NET, neuroendocrine tumor, medicine, Lung cancer, Liver metastasis, Pathological, Survival rate, FDG-PET, 18F-fluorodeoxyglucose positron emission tomography, Lung, business.industry, Large cell neuroendocrine carcinoma, ProGRP, progastrin-releasing peptide, respiratory system, medicine.disease, SCLC, small cell lung carcinoma, respiratory tract diseases, CT, computed tomography, medicine.anatomical_structure, S7, segment 7, Laparoscopic hepatectomy, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Surgery, Radiology, Hepatectomy, medicine.symptom, business, MRI, magnetic resonance imaging

الوصف: Highlights • Lung large-cell neuroendocrine carcinoma (LCNEC) is an aggressive and a rare type of lung cancer. • The prognosis of LCNEC with distant metastasis is extremely poor. • Surgical resection for liver metastasis of LCNEC may improve prognosis.
Introduction Lung large-cell neuroendocrine carcinoma (LCNEC) is an aggressive and a rare type of lung cancer, and the prognosis of LCNEC with distant metastasis is extremely poor, with a five-year survival rate of 0%. Here, we report a case of laparoscopic hepatectomy for liver metastasis of lung LCNEC. Presentation of case A 63-year-old man received a routine physical examination, and abnormal chest radiographic findings were observed; chest computed tomography (CT) in our hospital revealed that the patient had left pneumothorax and a lesion measuring 18 mm in the inferior lingular segment of the lung. The patient underwent thoracoscopic lobectomy, and the final pathological diagnosis was lung LCNEC. Four years after surgery, abdominal CT revealed a mass measuring 27 mm in the liver. The patient underwent laparoscopic partial hepatectomy, and postoperative pathological examination showed liver metastasis of LCNEC. There was no sign of recurrence 6 months after hepatectomy. Discussion LCNEC with distant metastasis has a poor response to systemic chemotherapy, and the median survival time of patients with distant metastasis is estimated to be approximately 6 months, with a five-year survival rate of 0%. Although the common site of metastasis from LCNEC is the liver, there are no previous reports of hepatectomy for liver metastasis of LCNEC. Conclusion We report a case of laparoscopic hepatectomy for liver metastasis of lung LCNEC. It is suggested that surgical resection for solitary distant metastasis of LCNEC may improve prognosis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::86d54915c214183b0b9d43c54ea283c4Test
https://doi.org/10.1016/j.ijscr.2019.10.026Test

المؤلفون: Daniel Rouison, Manish Kohli, Thierry Cousin, Pierre Liaud, George Garnier, Frederic Berthier, Mélina Blairvacq, Dominique Joubert, Berengere Vire, Léa Payen, Winston Tan, Alexandre Prieur

المصدر: Cancers
Volume 13
Issue 3
Cancers, Vol 13, Iss 375, p 375 (2021)

مصطلحات موضوعية: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, endocrine system, urologic and male genital diseases, lcsh:RC254-282, 03 medical and health sciences, Risk model, 0302 clinical medicine, Risk groups, Renal cell carcinoma, Internal medicine, medicine, IMDC, In patient, circulating progastrin, Receiver operating characteristic, business.industry, Significant difference, Area under the curve, medicine.disease, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, hPG80, Keywords: metastatic renal cell carcinoma (mRCC), 030104 developmental biology, blood-based prognostic biomarker, metastatic renal cell carcinoma (mRCC), 030220 oncology & carcinogenesis, business, Kidney cancer

الوصف: Precise management of kidney cancer requires the identification of prognostic factors. hPG80 (circulating progastrin) is a tumor promoting peptide present in the blood of patients with various cancers, including renal cell carcinoma (RCC). In this study, we evaluated the prognostic value of plasma hPG80 in 143 prospectively collected patients with metastatic RCC (mRCC). The prognostic impact of hPG80 levels on overall survival (OS) in mRCC patients after controlling for hPG80 levels in non-cancer age matched controls was determined and compared to the International Metastatic Database Consortium (IMDC) risk model (good, intermediate, poor). ROC curves were used to evaluate the diagnostic accuracy of hPG80 using the area under the curve (AUC). Our results showed that plasma hPG80 was detected in 94% of mRCC patients. hPG80 levels displayed high predictive accuracy with an AUC of 0.93 and 0.84 when compared to 18&ndash
25 year old controls and 50&ndash
80 year old controls, respectively. mRCC patients with high hPG80 levels (>
4.5 pM) had significantly lower OS compared to patients with low hPG80 levels (<
4.5 pM) (12 versus 31.2 months, respectively
p = 0.0031). Adding hPG80 levels (score of 1 for patients having hPG80 levels >
4.5 pM) to the six variables of the IMDC risk model showed a greater and significant difference in OS between the newly defined good-, intermediate- and poor-risk groups (p = 0.0003 compared to p = 0.0076). Finally, when patients with IMDC intermediate-risk group were further divided into two groups based on hPG80 levels within these subgroups, increased OS were observed in patients with low hPG80 levels (<
4.5 pM). In conclusion, our data suggest that hPG80 could be used for prognosticating survival in mRCC alone or integrated to the IMDC score (by adding a variable to the IMDC score or by substratifying the IMDC risk groups), be a prognostic biomarker in mRCC patients.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::55203daeb0428300383f23a97d4db325Test

المؤلفون: Martina Fontana, Franco Keller, Luca Ceriani, Luca Giovanella, Gaetano Paone, Alfredo Campennì

مصطلحات موضوعية: Oncology, medicine.medical_specialty, Medullary cavity, Clinical Biochemistry, 030209 endocrinology & metabolism, Thyroid carcinoma, 03 medical and health sciences, 0302 clinical medicine, Carcinoembryonic antigen, Internal medicine, Gastrin-releasing peptide, Biomarkers, Tumor, medicine, Humans, calcitonin, carcinoembryonic antigen, medullary thyroid carcinoma, progastrin releasing peptide (ProGRP), thyroid tumor, Thyroid Neoplasms, Tumor marker, biology, business.industry, Biochemistry (medical), Thyroid, Medullary thyroid cancer, General Medicine, medicine.disease, Peptide Fragments, Recombinant Proteins, Carcinoembryonic Antigen, Carcinoma, Neuroendocrine, medicine.anatomical_structure, Gastrin-Releasing Peptide, Calcitonin, 030220 oncology & carcinogenesis, biology.protein, business

الوصف: Objectives Serum calcitonin (CT) is pivotal in medullary thyroid cancer (MTC) management. Recently, progastrin releasing peptide (ProGRP) has been proposed as a candidate complementary tumor marker of MTC. As current data are sparse our study was undertaken to evaluate the distribution of ProGRP in patients with MTC and its relationship with the tumor burden. Additionally, serial measurement of CT, carcinoembryonic antigen (CEA) and ProGRP was evaluated in three patients undergoing tyrosine kinase inhibitors (TKI). Methods Seventy-eight, 125 and 62 sera from patients with MTC, non-medullary malignant and benign thyroid diseases were collected, respectively. ProGRP measurement was performed by Elecsys® assays on Cobas e601 platform (Roche Diagnostics). Results Significantly higher ProGRP levels were found in MTC compared to non-MTC patients. Among MTC patients ProGRP levels accurately discriminate patients with active from those with cured disease and, respectively, patients with loco-regional active disease from those with distant metastasis. Finally, ProGRP performed better than CT and CEA in monitoring the response to TKI therapy in three patients monitored serially. Conclusions Serum ProGRP is promising as a complementary tumor marker in MTC patients. Further studies will be required, mainly focused on monitoring ProGRP during TKI treatment for early detection of resistance and assessing its usefulness to avoid the observed false positive fluctuations that occur with CT and carcinoembryonic antigen.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3bc520470e151527bcc74c4c55cae816Test
http://hdl.handle.net/11570/3212244Test

المؤلفون: Wenchu Lin, Yang Zhang, Wei Wang, Li-ting Qian, Dan Li, Ming Li, Chunyang Dai, Dandan Han

المصدر: Oncology Letters

مصطلحات موضوعية: 0301 basic medicine, Oncology, therapeutic monitoring, Cancer Research, medicine.medical_specialty, medicine.medical_treatment, Enolase, progastrin-releasing peptide, Drug resistance, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, small-cell lung cancer, medicine, Chemotherapy, Oncogene, Receiver operating characteristic, business.industry, Cancer, Articles, medicine.disease, Molecular medicine, neuron-specific enolase, respiratory tract diseases, 030104 developmental biology, 030220 oncology & carcinogenesis, Biomarker (medicine), business

الوصف: The utility of serum progastrin-releasing peptide (ProGRP) and neuron-specific enolase (NSE) as biomarkers for treatment monitoring and as prognostic factors was investigated in small cell lung cancer (SCLC) patients. Patients were first diagnosed pathologically at the First Affiliated Hospital of the University of Science and Technology of China and had their serum ProGRP and NSE levels measured using an electrochemiluminescence immunoassay. A total of 120 SCLC patients were enrolled. In responsive patients, ProGRP levels decreased significantly following two cycles of chemotherapy and continued to decline over the course of treatment. However, this decrease in ProGRP levels was not observed in non-responsive patients. Changes in ProGRP levels were more accurate than changes in NSE levels for monitoring the effects of chemotherapy in patients with SCLC. Following two treatment cycles or after the occurrence of drug resistance, changes in ProGRP levels in patients with low ProGRP levels at the time of diagnosis were not notably, regardless of whether or not patients were responders. The area under the receiver operating characteristic curve of the decline in ProGRP levels as a therapeutic biomarker of SCLC was 0.9643, and the cut-off value was 55.02%. A decline in ProGRP levels maybe a good predictor of objective response to chemotherapy in patients with SCLC with higher ProGRP levels at diagnosis. This model is expected to replace or be combined with imaging to predict chemotherapeutic treatment effects in patients with SCLC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2f6a3306e3d49a896d7222b05d628c28Test
https://doi.org/10.3892/ol.2020.12164Test

المؤلفون: Vahan Kepenekian, Veronique Saywell, Laurent Villeneuve, Benoit You, Pierre Liaud, Berengere Vire, Frederic Mercier, Delphine Maucort-Boulch, Winston Tan, Alexandre Prieur, Julien Soulé, Maud Flacelière, Philippe Elies, Manish Kohli, Olivier Glehen, Carole Langlois-Jacques, Fanny Belouin, Dominique Joubert, Thibault Mazard, E. Assenat, Marc Ychou, Lea Payen, Eric Morency, Marie Dupuy

المساهمون: Service d'Oncologie Médicale [Centre hospitalier Lyon Sud - HCL], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Eurobiodev, Institut de Génétique Moléculaire de Montpellier (IGMM), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire d'InfoRmatique en Image et Systèmes d'information (LIRIS), Université Lumière - Lyon 2 (UL2)-École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biométrie et Biologie Evolutive - UMR 5558 (LBBE), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de Recherche en Informatique et en Automatique (Inria)-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon, Université de Bretagne Occidentale - UFR Médecine et Sciences de la Santé (UBO UFR MSS), Université de Brest (UBO), Institut du Cancer de Montpellier (ICM), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Dpt of Oncology [Rochester], Mayo Clinic, Hospices Civils de Lyon (HCL), ECS Progastrin, Salvy-Córdoba, Nathalie, Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Lumière - Lyon 2 (UL2)

المصدر: EBioMedicine
EBioMedicine, 2020, 51, pp.102574. ⟨10.1016/j.ebiom.2019.11.035⟩
EBioMedicine, Elsevier, 2020, 51, pp.102574. ⟨10.1016/j.ebiom.2019.11.035⟩
EBioMedicine, Vol 51, Iss, Pp-(2020)

مصطلحات موضوعية: Male, [SDV.MHEP.HEM] Life Sciences [q-bio]/Human health and pathology/Hematology, 0301 basic medicine, MESH: Protein Precursors, Research paper, MESH: Oncogenes, Antibodies, Neoplasm, Colorectal cancer, Druggability, lcsh:Medicine, MESH: Spheroids, Cellular, MESH: Gastrins, Neutralization, Cohort Studies, MESH: Aged, 80 and over, 0302 clinical medicine, Neoplasms, Medicine, MESH: Neoplasms, MESH: Cohort Studies, MESH: Organ Specificity, Cancer, Aged, 80 and over, MESH: Aged, lcsh:R5-920, MESH: Middle Aged, MESH: Kinetics, Progastrin, [SDV.MHEP.HEM]Life Sciences [q-bio]/Human health and pathology/Hematology, MESH: Gene Expression Regulation, Neoplastic, General Medicine, Middle Aged, 3. Good health, Peritoneal carcinomatosis, Gene Expression Regulation, Neoplastic, Organ Specificity, MESH: Young Adult, 030220 oncology & carcinogenesis, Immunohistochemistry, Female, lcsh:Medicine (General), Adult, MESH: Cell Line, Tumor, Monitoring, Blood biomarker, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, General Biochemistry, Genetics and Molecular Biology, Young Adult, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cancer stem cell, Cell Line, Tumor, Spheroids, Cellular, MESH: Cell Proliferation, Gastrins, Humans, RNA, Messenger, Protein Precursors, Gene, Aged, Cell Proliferation, MESH: RNA, Messenger, MESH: Humans, hPG80, business.industry, lcsh:R, MESH: Adult, Oncogenes, medicine.disease, MESH: Male, Kinetics, MESH: Antibodies, Neoplasm, 030104 developmental biology, Cancer research, MESH: Antineoplastic Agents, Therapy, business, MESH: Female

الوصف: Background: In colorectal cancer, hPG80 (progastrin) is released from tumor cells, promotes cancer stem cells (CSC) self-renewal and is detected in the blood of patients. Because the gene GAST that encodes hPG80 is a target gene of oncogenic pathways that are activated in many tumor types, we hypothesized that hPG80 could be expressed by tumors from various origins other than colorectal cancers, be a drug target and be detectable in the blood of these patients. Methods: hPG80 expression was monitored by fluorescent immunohistochemistry and mRNA expression in tumors from various origins. Cancer cell lines were used in sphere forming assay to analyze CSC self-renewal. Blood samples were obtained from 1546 patients with 11 different cancer origins and from two retrospective kinetic studies in patients with peritoneal carcinomatosis or hepatocellular carcinomas. These patients were regularly sampled during treatments and assayed for hPG80. Findings: We showed that hPG80 was present in the 11 tumor types tested. In cell lines originating from these tumor types, hPG80 neutralization decreased significantly CSC self-renewal by 28 to 54%. hPG80 was detected in the blood of patients at significantly higher concentration than in healthy blood donors (median hPG80: 4.88 pM versus 1.05 pM; p

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::451983d1ed4c6399869f84f0b5b8feaaTest
https://doi.org/10.1016/j.ebiom.2019.11.035Test

المؤلفون: Aakash Gajjar, Shubhashish Sarkar, Pomila Singh, Carla Kantara, Malaney R. O'Connell, Gurinder Luthra, Robert L. Ullrich

المصدر: Laboratory investigation; a journal of technical methods and pathology

مصطلحات موضوعية: Pathology, medicine.medical_specialty, Colorectal cancer, DCLK1, Green Fluorescent Proteins, Mice, Nude, Article, Pathology and Forensic Medicine, Metastasis, Mice, 03 medical and health sciences, LGR5, 0302 clinical medicine, Recurrence, Cancer stem cell, medicine, Animals, Humans, CD44, Neoplasm Metastasis, Molecular Biology, Annexin A2, 030304 developmental biology, Mice nude, 0303 health sciences, business.industry, Progastrin, CK19, Circulating CSCs, Cell Biology, Neoplastic Cells, Circulating, medicine.disease, 3. Good health, 030220 oncology & carcinogenesis, Colonic Neoplasms, Neoplastic Stem Cells, Cancer research, business

الوصف: Cancer stem cells (CSCs) are believed to be resistant to currently available therapies and may be responsible for relapse of cancer in patients. Measuring circulating tumor cells (CTCs) in the blood of patients has emerged as a non-invasive diagnostic procedure for screening patients who may be at high risk for developing metastatic cancers or relapse of the cancer disease. However, accurate detection of CTCs has remained a problem, as epithelial-cell markers used to date are not always reliable for detecting CTCs, especially during epithelial-mesenchymal transition. As CSCs are required to initiate metastatic tumors, our goal was to optimize and standardize a method for identifying circulating CSCs (CCSCs) in patients, using established CSC markers. Here, we report for the first time the detection of CCSCs in the blood of athymic nude mice, bearing metastatic tumors, and in the blood of patients positive for colonic adenocarcinomas. Using a simple and non-expensive method, we isolated a relatively pure population of CSCs (CD45-/CK19+), free of red blood cells and largely free of contaminating CD45+ white blood cells. Enriched CCSCs from patients with colon adenocarcinomas had a malignant phenotype and co-expressed CSC markers (DCLK1/LGR5) with CD44/Annexin A2. CSCs were not found in the blood of non-cancer patients, free of colonic growths. Enriched CCSCs from colon cancer patients grew primary spheroids, suggesting the presence of tumor-initiating cells in the blood of these patients. In conclusion, we have developed a novel diagnostic assay for detecting CSCs in circulation, which may more accurately predict the risk of relapse or metastatic disease in patients. As CSCs can potentially initiate metastatic growths, patients positive for CCSCs can be treated with inhibitory agents that selectively target CSCs, besides conventional treatments, to reduce the risk of relapse/metastatic disease for improving clinical outcomes.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::eba594e19e4c20dfe4f2e7a56bb7d402Test
https://doi.org/10.1038/labinvest.2014.133Test

المؤلفون: Hongshan Wang, Yagnesh Tailor, Kosuke Sakitani, Guangchun Jin, Timothy C. Wang, Ying Jin, Daniel L. Worthley, Alexander Dubeykovskiy

المصدر: Oncotarget

مصطلحات موضوعية: 0301 basic medicine, Colorectal cancer, Carcinogenesis, Apoptosis, medicine.disease_cause, Receptors, G-Protein-Coupled, chemistry.chemical_compound, 0302 clinical medicine, Intestinal Mucosa, Mice, Knockout, Stem Cells, 3. Good health, Oncology, 030220 oncology & carcinogenesis, Colonic Neoplasms, Stem cell, Protein Binding, Research Paper, Genetically modified mouse, medicine.medical_specialty, Colon, proliferation, Mice, Transgenic, colorectal cancer, 03 medical and health sciences, progastrin, Internal medicine, Cell Line, Tumor, Gastrins, medicine, Animals, Humans, Protein Precursors, Cell Proliferation, Azoxymethane, business.industry, medicine.disease, digestive system diseases, Receptor, Cholecystokinin B, Mice, Inbred C57BL, stem cell, 030104 developmental biology, Endocrinology, GPR56, chemistry, Cancer cell, Cancer research, business

الوصف: // Guangchun Jin 1, 2 , Kosuke Sakitani 1 , Hongshan Wang 1, 3 , Ying Jin 1 , Alexander Dubeykovskiy 1 , Daniel L. Worthley 4 , Yagnesh Tailor 1 and Timothy C. Wang 1 1 Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY, USA 2 The Research Institute, Yanbian University Hospital, Jilin, China 3 Department of General surgery, Zhongshan Hospital, Fudan University, Shanghai, China 4 South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, South Australia, Australia Correspondence to: Timothy C. Wang, email: tcw21@columbia.edu Keywords: GPR56, progastrin, proliferation, stem cell, colorectal cancer Abbreviations: Human progastrin (hGAS), G-protein coupled receptor 56 (GPR56), 5-bromo-2’-deoxyuridine (BrdU), Bone morphogenetic protein (BMP). Received: November 02, 2016 Accepted: February 22, 2017 Published: March 23, 2017 ABSTRACT Overexpression of human progastrin increases colonic mucosal proliferation and colorectal cancer progression in mice. The G-protein coupled receptor 56 (GPR56) is known to regulate cell adhesion, migration, proliferation and stem cell biology, but its expression in the gut has not been studied. We hypothesized that the promotion of colorectal cancer by progastrin may be mediated in part through GPR56. Here, we found that GPR56 expresses in rare colonic crypt cells that lineage trace colonic glands consistent with GPR56 marking long-lived colonic stem-progenitor cells. GPR56 was upregulated in transgenic mice overexpressing human progastrin. While recombinant human progastrin promoted the growth and survival of wild-type colonic organoids in vitro , colonic organoids cultured from GPR56 −/− mice were resistant to progastrin. We found that progastrin directly bound to, and increased the proliferation of, GPR56-expressing colon cancer cells in vitro , and proliferation was increased in cells that expressed both GPR56 and the cholecystokinin-2 receptor (CCK2R). In vivo , deletion of GPR56 in the mouse germline abrogated progastrin-dependent colonic mucosal proliferation and increased apoptosis. Loss of GPR56 also inhibited progastrin-dependent colonic crypt fission and colorectal carcinogenesis in the azoxymethane (AOM) mouse model of colorectal cancer. Overall, we found that progastrin binds to GPR56 expressing colonic stem cells, which in turn promotes their expansion, and that this GPR56-dependent pathway is an important driver and potential new target in colorectal carcinogenesis.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::03232161df6d8b9d2083339d7c1dd1aeTest
https://pubmed.ncbi.nlm.nih.gov/28380450Test

المؤلفون: Shine Young Kim, Jin-Hyun Lee, Maria Hong, Ji-In Yu, Seul-Ki Park, Jae-Eun Lee, So-Youn Shin

المصدر: Osong Public Health and Research Perspectives

مصطلحات موضوعية: chemistry.chemical_classification, Plasma samples, Sample processing, Public Health, Environmental and Occupational Health, Peptide, Serum samples, cryopreservation, Cryopreservation, Andrology, biobank, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, chemistry, Biochemistry, 030220 oncology & carcinogenesis, Original Article, 030212 general & internal medicine, Non small cell, serum, plasma, progastrin-releasing peptide stability

الوصف: ObjectivesProgastrin-releasing peptide (proGRP) is a promising biomarker for small cell lung cancer. However, not much is known about how sample processing and storage conditions affect the stability of proGRP. Here, we examined the effects of repeated freeze–thaw cycles on the stability of proGRP in plasma and serum.MethodsConcentrations of proGRP were measured in plasma and serum samples exposed to two, three, or four freeze–thaw cycles and these were compared with values of corresponding samples exposed to one cycle (baseline). We also performed the area under the receiver-operating-characteristic curve (AUC) analysis to determine whether the differences of proGRP concentrations between each paired plasma and serum sample (ΔproGRP) can be used for identifying the samples that have been exposed to multiple freeze–thaw cycles.ResultsConcentrations of proGRP gradually decreased in both plasma and serum samples with increasing numbers of freeze–thaw cycles. Reduction rates of proGRP concentrations were greater in serum than in plasma samples and serum proGRP levels declined with statistical significance (p < 0.001) up to 10.1% after four freeze–thaw cycles. The ΔproGRP measurement showed fair accuracy (AUC = 0.741) for identifying samples that had been through four freeze–thaw cycles. The sensitivity was 82.8% and specificity was 62.1% at an optimal cut-off point of > 4.9.ConclusionOur study shows that the stability of circulating proGRP is affected in both plasma and serum samples by repeated freezing and thawing. We also show that ΔproGRP could be used for identifying paired plasma and serum samples subjected to multiple freeze–thaw cycles.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3184c8901aa4f3086f3dc2450ceb6cbfTest