المؤلفون: Qiang He, Jian Luo, Jin-Zhi Xu, Chun-xia Wang, Xian-zhi Meng, Guo-Qing Pan, Tian Li, Ze-Yang Zhou

المصدر: mSphere, Vol 5, Iss 1 (2020)

مصطلحات موضوعية: sporoplasm, microsporidia, Nosema bombycis, morphology, infection mechanism, transcriptome, Microbiology, QR1-502

الوصف: ABSTRACT Microsporidia are obligate intracellular parasites that infect a wide variety of host organisms, including humans. The sporoplasm is the initial stage of microsporidian infection and proliferation, but its morphological and molecular characteristics are poorly understood. In this study, the sporoplasm of Nosema bombycis was successfully isolated and characterized after the induction of spore germination in vitro. The sporoplasm was spherical, 3.64 ± 0.41 μm in diameter, had the typical two nuclei, and was nonrefractive. Scanning and transmission electron microscopy analyses revealed that the sporoplasm was surrounded by a single membrane, and the cytoplasm was usually filled with relatively homogeneous granules, possibly ribosomes, and contained a vesicular structure comprising a concentric ring and coiled tubules. Propidium iodide staining revealed that the sporoplasm membrane showed stronger membrane permeability than did the cell plasma membrane. Transmission electron microscopy (TEM) revealed that the sporoplasm can gain entry to the host cell by phagocytosis. Transcriptome analysis of mature spores and sporoplasms showed that 541 significantly differentially expressed genes were screened (adjusted P value [Padj] < 0.05), of which 302 genes were upregulated and 239 genes were downregulated in the sporoplasm. The majority of the genes involved in trehalose synthesis metabolism, glycolysis, and the pentose phosphate pathway were downregulated, whereas 10 transporter genes were upregulated, suggesting that the sporoplasm may inhibit its own carbon metabolic activity and obtain the substances required for proliferation through transporter proteins. This study represents the first comprehensive and in-depth investigation of the sporoplasm at the morphological and molecular levels and provides novel insights into the biology of microsporidia and their infection mechanism. IMPORTANCE Once awoken from dormancy, the cellular matter of microsporidia is delivered directly into the host cell cytoplasm through the polar tube. This means that the microsporidia are difficult to study biologically in their active state without a contaminating signal from the host cell. Sporoplasm is a cell type of microsporidia in vitro, but relatively little attention has been paid to the sporoplasm in the past 150 years due to a lack of an effective separation method. Nosema bombycis, the first reported microsporidium, is a type of obligate intracellular parasite that infects silkworms and can be induced to germinate in alkaline solution in vitro. We successfully separated the N. bombycis sporoplasm in vitro, and the morphological and structural characteristics were investigated. These results provide important insight into the biology and pathogenesis of microsporidia and potentially provide a possible strategy for genetic manipulation of microsporidia targeting the sporoplasm.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2379-5042Test

الوصول الحر: https://doaj.org/article/d6e0787cc5e74e90b1a02efa28405d79Test

المؤلفون: Xianzhi Meng, Tian Li, Guoqing Pan, Chen Xu, Chunfeng Li, Jin-Zhi Xu, Jian Luo, Bin Yu, Zeyang Zhou

المصدر: International Journal of Molecular Sciences, Vol 22, Iss 5051, p 5051 (2021)
International Journal of Molecular Sciences
Volume 22
Issue 9

مصطلحات موضوعية: 0301 basic medicine, animal structures, organelle, Nucleolus, QH301-705.5, viruses, proteome, computer.software_genre, Genome, Catalysis, Inorganic Chemistry, 03 medical and health sciences, Bombyx mori, Organelle, Physical and Theoretical Chemistry, Biology (General), silkworm, Molecular Biology, Gene, QD1-999, Spectroscopy, database, 030102 biochemistry & molecular biology, biology, Database, Endoplasmic reticulum, Organic Chemistry, fungi, General Medicine, biology.organism_classification, Computer Science Applications, Chemistry, 030104 developmental biology, GenBank, Proteome, computer

الوصف: Silkworm Bombyx mori is an economically important insect and a lepidopteran model. Organelle proteome is vital to understanding gene functions
however, it remains to be identified in silkworm. Here, using the engineered ascorbate peroxidase APEX, we constructed transgenic B. mori embryo cells (BmE) expressing APEX-NLS, COX4-APEX, APEX-Rev, and APEX-KDEL in nucleus, mitochondrial matrix (MM), cytosol, and endoplasmic reticulum (ER), and isolated the biotin-labeled proteins using streptavidin-affinity purification, respectively. The isolated proteins were determined using LC-MS/MS and annotated by searching B. mori genomes downloaded from GenBank, SilkBase, SilkDB 2.0, and SilkDB 3.0, resulting in 842, 495, 311, and 445 organelle proteins identified, respectively. We mapped the 296 MM proteins annotated in the GenBank data to mitochondrial protein databases of the fly, human, and mouse, and found that 140 (47%) proteins are homologous to 80 fly proteins, and 65 (22%) proteins match to 31 and 29 human and mouse proteins, respectively. Protein orthology was predicted in multiple insects using OrthoMCL, producing 460 families containing 839 proteins we identified. Out of 460 families, 363 were highly conserved and found in all insects, leaving only three proteins without orthology in other insects, indicating that the identified proteins are highly conserved and probably play important roles in insects. A gene ontology enrichment analysis by clusterProfiler revealed that the nucleus proteins significantly enriched in cellular component terms of nucleus and nucleolus, the MM proteins markedly enriched in molecular function terms of nucleotide binding, and the cytosol proteins mainly enriched in biological process terms of small molecule metabolism. To facilitate the usage and analysis of our data, we developed an open-access database, Silkworm Organelle Proteome Database (SilkOrganPDB), which provides multiple modules for searching, browsing, downloading, and analyzing these proteins, including BLAST, HMMER, Organelle Proteins, Protein Locations, Sequences, Gene Ontology, Homologs, and Phylogeny. In summary, our work revealed the protein composition of silkworm BmE organelles and provided a database resource helpful for understanding the functions and evolution of these proteins.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::56bd5f79a526238ea38c725db3e8a9daTest
https://www.mdpi.com/1422-0067/22/9/5051Test

المؤلفون: Rafael Morales-Barrera, Daniel E. Castellano, Peter H. O'Donnell, Petros Grivas, Jacqueline Vuky, Thomas Powles, Kylea R. Potvin, Susanna Y. Cheng, Eli Rosenbaum, Noah M. Hahn, Daniel Keizman, Fausto Roila, Jose Luis Perez-Gracia, Elizabeth R. Plimack, Ronald De Wit, Jin Zhi Xu, Kentaro Imai, Haojie Li, Josephine M. Norquist, Joaquim Bellmunt

المصدر: Journal of Clinical Oncology. 40:4561-4561

مصطلحات موضوعية: Cancer Research, Oncology

الوصف: 4561 Background: Frontline cisplatin-based chemotherapy improves survival in patients (pts) with UC, but ̃50% are cisplatin-ineligible owing to poor performance status or comorbidity. The definition of platinum ineligibility is not standardized; hence, treatment decisions are almost solely made by clinical judgment. Pembrolizumab (pembro) showed antitumor activity and manageable toxicity as frontline therapy in 370 cisplatin-ineligible pts in the single arm, phase 2 KEYNOTE-052 trial (NCT02335424). We present effects of pembro on HRQoL of pts in KEYNOTE-052 who were potentially platinum ineligible in this exploratory analysis. Methods: Eligible pts for KEYNOTE-052 were adults with no prior systemic chemotherapy for advanced/metastatic UC, ECOG PS ≤2, and measurable disease per RECIST v1.1 by blinded independent central review. Pembro 200 mg IV was administered Q3W for up to 2 y. Clinical characteristics of frail pts (platinum ineligible) were identified by extensive review of real-world treatment patterns and relevant literature. Consequently, platinum ineligibility was defined as having an ECOG PS ≥2 plus ≥1 of the following: visceral disease, creatinine clearance < 60 mL/min, or age ≥80 y. HRQoL was assessed using the EORTC QLQ-C30 and EQ-5D-3L during the first 4 cycles, then every 2 cycles for 1 year or until treatment discontinuation (whichever occurred first), and at least 30 days after treatment discontinuation. Key end points were change from baseline per the QLQ-C30 global health status (GHS)/QoL score, QLQ-C30 physical functioning subscale, and EQ-5D visual analog scale (VAS). The minimum important difference (MID) was 10 for QLQ-C30 score change (improved: ≥10; stable: –10 to 10; deteriorated: –10 or less); MID for VAS score change was 7 (improved: ≥7; stable: –7 to 7; deteriorated: –7 or less). Results: Median age for 143 pts was 75 y (range, 34-91); 129 pts (90.2%) had visceral disease; 142 (99.3%) had ECOG PS 2; 1 had ECOG PS 3 (enrolled in error). Compliance rate for HRQoL questionnaires was 93.7% at baseline. At the prespecified analysis time of week 9, 77.6% of pts had improved (n = 51) or stable (n = 60) QLQ-C30 GHS/QoL scores, 64.3% had improved (n = 35) or stable (n = 57) QLQ-C30 physical functioning scores, and 62.2% had improved (n = 56) or stable (n = 33) EQ-5D VAS scores. These scores were stable throughout the HRQoL assessment period for pts who continued pembro. Conclusions: In this exploratory analysis, pembro maintained HRQoL for pts with advanced/metastatic UC in KEYNOTE-052 who were potentially platinum-ineligible per the above criteria. Together with the efficacy and safety data from KEYNOTE-052, these data suggest that pembro monotherapy is a valuable treatment option for select pts with advanced UC who are more senior and/or deemed medically frail. Clinical trial information: NCT02335424.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::03684d61419b5114fede9b528ab7ad85Test
https://doi.org/10.1200/jco.2022.40.16_suppl.4561Test

المؤلفون: Tian Li, Hailong Gao, Zeyang Zhou, Jian Luo, Jiajing Chen, Yinze Han, Chunxia Wang, Bing Han, Boyan Pei, Jin-Zhi Xu, Bin Yu

مصطلحات موضوعية: medicine.anatomical_structure, Encephalitozoon hellem, Downregulation and upregulation, Chemistry, Host (biology), medicine, Endoplasmic-reticulum-associated protein degradation, Nucleus, Protein ubiquitination, Cell biology

الوصف: Background: Microsporidia, a group of obligate intracellular parasites that can infect humans and nearly all animals, have lost the pathways for de novo amino acid, lipid and nucleotide synthesis and instead evolved strategies to manipulate host metabolism and immunity. The endoplasmic reticulum (ER) is a vital organelle for producing and processing proteins and lipids and is often hijacked by intracellular pathogens. However, little is known about how microsporidia modulate host ER pathways. Herein, we identified a secreted protein of Encephalitozoon hellem, EhHNTP1, and characterized its subcellular localization and functions in host cells.Methods: A polyclonal antibody against EhHNTP1 was produced to verify the protein subcellular localization in E. hellem-infected cells using indirect immunofluorescence assay (IFA) and Western blotting. HEK293 cells were transfected with wild-type or mutant EhHNTP1 fused with HA-EGFP, and the impacts on pathogen proliferation, protein subcellular localization and sequence functions were assessed. RNA sequencing of EhHNTP1-transfected cells was conducted to identify differentially expressed genes (DEGs) and pathway responses by bioinformatics analysis mainly with R packages. The DEGs in the transfected cells were experimentally confirmed with RT-qPCR and Western blotting. The regulatory effects of candidate DEGs were analyzed via RNA interference and cell transfection, and the effects were determined with RT-qPCR and Western blotting.Results: EhHNTP1 is secreted into the host nucleus, and its translocation depends on a nuclear localization signal sequence (NLS) at the C-terminus from amino acids 239 to 250. Transfection and overexpression of EhHNTP1 in HEK293 cells significantly promoted pathogen proliferation. RNA-seq of the transfected cells showed that genes involved in ER-associated degradation (ERAD), a quality control mechanism that allows for the targeted degradation of proteins in the ER, were prominently upregulated. Upregulation of the ERAD genes PDIA4, HERP, HSPA5 and Derlin3 determined by RNA-seq data was verified using RT-qPCR and Western blotting. Protein ubiquitination in the transfected cells was then assayed and found to be markedly increased, confirming the activation of ERAD. PDIA4 knockdown with RNAi significantly suppressed the expression of HERP, indicating that PDIA4 is a vital ERAD component exploited by EhHNTP1. Moreover, EhHNTP1ΔHRD, a deletion mutant lacking the histidine-rich domain (HRD) in the C-terminus, predominantly suppressed the upregulation of ERAD genes, indicating that the HRD is essential for EhHNTP1 functions.Conclusion: This study is the first report on a microsporidian secretory protein that targets the host nucleus to upregulate the ERAD pathway and subsequently promote protein ubiquitination. Our work provides new insights into microsporidia-host interactions.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::a103c12b7737c11ef8cc5943bf0a63d6Test
https://doi.org/10.21203/rs.3.rs-319485/v1Test

المؤلفون: Wen Quan Wang, Liang Liu, Hao Li, Wu Hu Zhang, Jin Xu, Shi Rong Zhang, Shuo Li, Hua Xiang Xu, Jin Zhi Xu, He Li Gao, Xianjun Yu, Chun Tao Wu

المصدر: Journal of Cancer. 10:4123-4131

مصطلحات موضوعية: 0301 basic medicine, animal structures, Tissue microarray, biology, business.industry, medicine.disease, medicine.disease_cause, Hedgehog signaling pathway, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Oncology, GLI1, CDKN2A, 030220 oncology & carcinogenesis, Pancreatic cancer, Cancer research, biology.protein, medicine, KRAS, Sonic hedgehog, business, Smoothened

الوصف: Background: Pancreatic ductal adenocarcinoma (PDAC) progression is mediated by mutations in driver genes and a complex stroma that is mainly dependent on the Sonic hedgehog (Shh) signaling pathway. However, the association between driver genes and Shh-pathway proteins and their potential prognostic significance remain unclear. Methods: We analyzed protein expressions of the KRAS, TP53, SMAD4, and CDKN2A/P16 driver genes and the Shh-pathway molecules, including Shh, glioma-associated oncogene (Gli) 1, Gli2, and smoothened (SMO) by immunohistochemistry using tissue microarrays in 237 patients with resectable PDAC and statistically determined their prognostic significance. Results: SMAD4lost mutation was associated with shorter survival outcomes [overall survival (OS): Hazard ratio (HR) 1.887, p < 0.001]; recurrence-free survival (RFS): HR 1.886, p < 0.001) and abnormal p53 immunolabeling was associated with poor OS (HR 1.436, p = 0.011) in patients with PDAC. The mutational status of p16 had no effect on patient survival. High levels of SMO and Gli1 expression were associated with poor survival outcomes in both univariate and multivariate analyses. Pearson's χ2 test showed a medium correlation between the SMAD4lost mutation and Shh (R = 0.343) and Gli1 (R = 0.505) expression levels (p < 0.001). Patients with the SMAD4lost mutation and high levels of Shh and Gli1 expression showed the poorest survival outcomes (RFS: HR 2.976; OS: HR 3.598; p < 0.001 for both) compared with other patients in the study. Conclusion: Loss of SMAD4 associated with a strongly activated Shh pathway resulted in poor survival outcomes in patients with resected PDAC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::a9051cf59c0b70dbca0f62f6e145d291Test
https://doi.org/10.7150/jca.30883Test

المؤلفون: Peter H. O'Donnell, Arjun Vasant Balar, Daniel E. Castellano, Ronald De Wit, David J. Vaughn, Thomas Powles, Jacqueline Vuky, Jae-Lyun Lee, Yves Fradet, Joaquim Bellmunt, Lawrence Fong, Daniel P. Petrylak, Winald R. Gerritsen, David I. Quinn, Stephane Culine, Dean F. Bajorin, Jin Zhi Xu, Kentaro Imai, Blanca Homet Moreno, Petros Grivas

المصدر: Journal of Clinical Oncology. 40:516-516

مصطلحات موضوعية: Cancer Research, Oncology

الوصف: 516 Background: Pembro showed antitumor activity in 1L and 2L for pts with UC in the single-arm, phase 2 KEYNOTE-052 study (NCT02335424) and the randomized phase 3 KEYNOTE-045 (NCT02256436) study, respectively. This post hoc exploratory analysis evaluated whether primary tumor location affected efficacy and safety of pembro (KEYNOTE-052; KEYNOTE-045) and chemotherapy (chemo; KEYNOTE-045). Methods: KEYNOTE-052 enrolled cisplatin-ineligible pts with advanced/metastatic UC who had not previously received systemic therapy; they received pembro (200 mg IV Q3W). KEYNOTE-045 enrolled pts with advanced/metastatic UC who had received platinum-containing chemo; pts were randomly assigned 1:1 to receive pembro (200 mg IV Q3W) or investigator’s choice of chemo (paclitaxel, docetaxel, or vinflunine). Both studies required pts to have measurable disease per RECIST v1.1. Upper tract (UT) UC included primary tumors in the renal pelvis or ureter; lower tract (LT) UC included primary tumors in the bladder or urethra. Pts with UT and LT disease (UT/LT) were classified as LT. Pts receiving pembro were treated until disease progression, unacceptable toxicity, or withdrawal of consent, for up to 2y. End points were PFS, ORR, and DOR per RECIST v1.1 by central radiology assessment and OS. Results: A total of 369 pembro-treated pts (68 UT; 301 LT [79 UT/LT]) from KEYNOTE-052 plus 270 pembro-treated pts (93 UT; 177 LT [33 UT/LT]) and 272 chemo-treated pts (94 UT; 178 LT) from KEYNOTE-045 were evaluated. Median follow-up from randomization to data cutoff (09/26/20 and 10/1/20, respectively) was ≥56 mo. Both studies enrolled a similar percentage of pts with PD-L1–positive tumors (25%-30%). PFS, ORR, DOR, and OS for pembro were consistent regardless of tumor location, although ORR for KEYNOTE-045 was lower for the UT group (Table). In the chemo arm of KEYNOTE-045, similar efficacy was observed regardless of tumor location or regimen. Grade 3-5 TRAEs occurred at similar rates in KEYNOTE-052 (19.1% UT; 21.6% LT) and KEYNOTE-045 (17.2% UT; 16.8% LT). Conclusions: In this exploratory analysis, pembro showed similar clinical activity and manageable safety regardless of primary UC tumor location. Clinical trial information: NCT02256436 and NCT02335424. [Table: see text]

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::bafbe209abdb3ecbfd414e1a37e58086Test
https://doi.org/10.1200/jco.2022.40.6_suppl.516Test

المؤلفون: Daniel E. Castellano, Arjun Vasant Balar, Peter H. O'Donnell, Petros Grivas, David J. Vaughn, Thomas Powles, Jacqueline Vuky, Jae-Lyun Lee, Yves Fradet, Joaquim Bellmunt, Miguel Ángel Climent, Nicholas J. Vogelzang, Elizabeth R. Plimack, Howard Gurney, Noah M. Hahn, Cora N. Sternberg, Jin Zhi Xu, Kentaro Imai, Blanca Homet Moreno, Ronald De Wit

المصدر: Journal of Clinical Oncology. 40:512-512

مصطلحات موضوعية: Cancer Research, Oncology

الوصف: 512 Background: Pembrolizumab (pembro) has shown efficacy in advanced/unresectable and metastatic UC (mUC). There is interest in determining whether pts should be treated subsequently with checkpoint inhibitors such as anti–PD-1 therapy if mUC responds then later progresses. Pembro retreatment after disease progression has shown efficacy in melanoma and NSCLC. This post hoc exploratory analysis investigated the efficacy of pembro retreatment for pts with advanced UC or mUC enrolled in KEYNOTE-045 and KEYNOTE-052 with a best overall response (BOR) of SD or better and whose disease progressed after discontinuation or completion of 2 y of therapy. Methods: The phase 3 KEYNOTE-045 trial (NCT02256436) was designed to compare the efficacy and safety of pembro vs chemotherapy (chemo) in pts with mUC that recurred/progressed on platinum containing chemo; ≤2 prior lines of systemic chemo for mUC were permitted. The phase 2 KEYNOTE-052 trial (NCT02335424) was designed to evaluate the efficacy and safety of first-line pembro in cisplatin-ineligible pts with advanced UC. In both studies, pembro was administered for up to 2 y; pts were eligible for retreatment if they stopped pembro after CR or had a BOR of CR, PR, or SD and completed 2 y of treatment. Pts must have investigator-confirmed radiographic PD after therapy cessation, have ECOG PS score 0-1, and not have received anticancer treatment after the last pembro dose. BOR to retreatment is reported. Results: At data cutoff for KEYNOTE-045 (Oct 1, 2020), 11 pts were retreated: 5 (45%) achieved objective response to retreatment (3 CR; 2 PR; Table) and 6 had SD, for a disease control rate (DCR; CR+PR+SD) of 100%. Median treatment-free interval was 7.7 mo (IQR, 3.6-16.5); median duration of retreatment was 11.4 mo (IQR, 7.6-12.0). Seven pts (64%) were alive at cutoff. At data cutoff for KEYNOTE-052 (Sep 26, 2020), 10 pts were retreated; 5 (50%) had objective response to retreatment (1 CR; 4 PR) and 4 had SD, for a DCR of 90%. Retreatment BOR was PD for 1 pt (10%). Median treatment-free interval was 13.0 mo (9.2-16.6); median duration of retreatment was 6.0 mo (IQR, 4.9-9.2). Four pts (40%) were alive at cutoff. Conclusions: Although the number of pts who received retreatment was small, objective responses were observed. The findings are generally consistent with observations from retreatment in other tumor types (e.g., melanoma). Clinical trial information: NCT02256436 and NCT02335424. [Table: see text]

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::e5a3ee2c3016a5da8b2884bc7ce9eaf2Test
https://doi.org/10.1200/jco.2022.40.6_suppl.512Test

المؤلفون: Chen Liu, Wei Jin, Hua Xiang Xu, Jin Zhi Xu, Liang Liu, Chun Tao Wu, Quanxing Ni, He Li Gao, Wen Quan Wang, Jin Xu, Jiang Long, Zi Hao Qi, Shi Rong Zhang, Shuo Li, Xianjun Yu

المصدر: Pancreatology. 18:671-677

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, CA-19-9 Antigen, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Kaplan-Meier Estimate, Adenocarcinoma, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Recurrence free survival, Late Recurrence, Biomarkers, Tumor, Humans, Medicine, Postoperative Period, 030212 general & internal medicine, Adjuvant chemoradiotherapy, Aged, Aged, 80 and over, Hepatology, business.industry, Membrane Proteins, Chemoradiotherapy, Adjuvant, Middle Aged, medicine.disease, Survival Analysis, Progression-Free Survival, digestive system diseases, Independent factor, Carcinoembryonic Antigen, Pancreatic Neoplasms, Treatment Outcome, CA-125 Antigen, 030220 oncology & carcinogenesis, Female, CA19-9, Lymph Nodes, Lymph, business, Radical resection, Follow-Up Studies

الوصف: To evaluate the prediction of benefits from adjuvant chemoradiotherapy by postoperative serum CA19-9, CA125 and CEA.The relations between benefits from adjuvant chemoradiotherapy and levels of postoperative serum CA19-9, CA125 and CEA were investigated in 804 pancreatic adenocarcinoma patients who received radical resection.Adjuvant chemoradiotherapy was an independent factor for late recurrence [12.2 vs. 8.5 months, P = 0.001 for recurrence free survival (RFS)] and long survival [23.7 vs. 17.0 months, P 0.001 for overall survival (OS)] in resected pancreatic adenocarcinoma. Postoperative serum CA19-9, CA125 and CEA were independent risk predictors for poor surgical outcome in pancreatic adenocarcinoma (P 0.001 for all). Adjuvant chemradiotherapy (hazard ratio: 0.359, 95% confidence interval: 0.253-0.510, P 0.001 for OS; hazard ratio: 0.522, 95% confidence interval: 0.387-0.705, P 0.001 for RFS) were confirmed to improve the surgical outcome in patients with abnormal levels of any one of the three postoperative markers, but not in patients with normal levels of the three postoperative markers. In the subgroup of patients with negative lymph node, its improvement of surgical outcome was also significant in patients with abnormal levels of any one of postoperative serum CA19-9, CA125 and CEA (hazard ratio: 0.412, 95% confidence interval: 0.244-0.698, P = 0.001 for OS; hazard ratio: 0.546, 95% confidence interval: 0.352-0.847, P = 0.007 for RFS).Postoperative serum CA19-9, CA125 and CEA could serve as predictors of response for adjuvant chemoradiotherapy even if the status of lymph nodes is negative.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3c50ed5f5ddd3c2db858b0a403a442caTest
https://doi.org/10.1016/j.pan.2018.05.479Test

المؤلفون: Shi-Rong Zhang, Lie Yao, Wen-Quan Wang, Jin-Zhi Xu, Hua-Xiang Xu, Wei Jin, He-Li Gao, Chun-Tao Wu, Zi-Hao Qi, Hao Li, Shuo Li, Quan-Xing Ni, Xian-Jun Yu, De-Liang Fu, Liang Liu

المصدر: Annals of Surgical Oncology. 25:3984-3993

مصطلحات موضوعية: Blood Platelets, Male, 0301 basic medicine, Platelet Count, Kaplan-Meier Estimate, Middle Aged, Risk Assessment, Disease-Free Survival, Pancreatic Neoplasms, Survival Rate, 03 medical and health sciences, 030104 developmental biology, 0302 clinical medicine, Platelet Glycoprotein GPIb-IX Complex, Oncology, 030220 oncology & carcinogenesis, Preoperative Period, Humans, Female, Surgery, Carcinoma, Pancreatic Ductal, Neoplasm Staging

الوصف: Platelets are believed to promote tumor growth and metastasis in several tumor types. The prognostic role of blood platelets in pancreatic ductal adenocarcinoma (PDAC) remains controversial, and the prognostic value of tumor-infiltrating platelets (TIPs) remains unknown.A total of 303 patients who underwent curative pancreatectomy for PDAC were enrolled from two independent centers in China and divided into three cohorts. Paired preoperative blood samples and surgical specimens from all patients were analyzed. The correlations between patient outcomes and preoperative blood platelet counts and the presence of TIPs, respectively, were analyzed. TIPs were identified by immunohistochemical staining of CD42b. Prognostic accuracy was estimated by concordance index (C-index) and Akaike information criterion (AIC).TIPs, but not preoperative blood platelet counts, were associated with overall survival (OS; all P 0.001) and recurrence-free survival (RFS; all P 0.001) in the training, testing, and validation sets. Positive CD42b expression predicted poor postsurgical survival. Incorporation of TIPs improved the predictive accuracy of the 8th edition American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system for OS in each of the three cohorts (C-index: 0.7164, 0.7569, and 0.7050, respectively; AIC: 472, 386, and 1019, respectively). The new predictor system was validated by incorporating TIPs with the 7th edition AJCC TNM staging system (C-index: 0.7052, 0.7623, and 0.7157; AIC: 476, 386, and 1015).TIPs were an independent prognostic factor that could be incorporated into the AJCC TNM staging system to refine risk stratification and predict surgical outcomes of patients with PDAC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::409b70757d0f61a4392da508466c4e22Test
https://doi.org/10.1245/s10434-018-6727-8Test

المؤلفون: He Li Gao, Hua Xiang Xu, Jin Zhi Xu, Hao Li, Shi Rong Zhang, Shuo Li, Zi Hao Qi, Wei Jin, Liang Liu, Quan Xing Ni, Xianjun Yu, Wen Quan Wang, Chun Tao Wu

المصدر: Angiogenesis. 22:15-36

مصطلحات موضوعية: 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, Standard of care, Physiology, Angiogenesis, Clinical Biochemistry, Angiogenesis Inhibitors, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Pancreatic cancer, medicine, Animals, Humans, Tumor growth, Survival rate, Therapeutic strategy, Microvessel density, Neovascularization, Pathologic, business.industry, Hematogenous metastasis, medicine.disease, Pancreatic Neoplasms, 030104 developmental biology, 030220 oncology & carcinogenesis, business

الوصف: Pancreatic cancer is one of the most lethal malignancies worldwide. Although the standard of care in pancreatic cancer has improved, prognoses for patients remain poor with a 5-year survival rate of

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::4c0f99b7be70b7bbd095b67e8f19a18bTest
https://doi.org/10.1007/s10456-018-9645-2Test