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Article ; Online: Hot Tub Lung: Case Report and Review of the Literature.

Gundacker, Nathan D / Gonzalez, Jose Anel / Sheinin, Yuri M / Hirschtritt, Todd

WMJ : official publication of the State Medical Society of Wisconsin

2022 Volume 121, Issue 2, Page(s) E31–E33

Abstract: Introduction: Nontuberculous mycobacteria-related hypersensitivity pneumonitits (NTM-HP), otherwise known as hot tub lung, is an uncommon disease produced by exposure to aerosolized hot tub water containing nontuberculous mycobacteria. Patients usually ... ...

Abstract	Introduction: Nontuberculous mycobacteria-related hypersensitivity pneumonitits (NTM-HP), otherwise known as hot tub lung, is an uncommon disease produced by exposure to aerosolized hot tub water containing nontuberculous mycobacteria. Patients usually present with nonspecific, prolonged respiratory symptoms and require a thorough respiratory workup, including radiography and even pulmonary biopsies. Case presentation: We present the case of a 58-year-old patient with chronic respiratory symptoms and history of exposure to a hot tub. Discussion: There is little data on why certain patients develop NTM-HP; however, it seems to be an immunologic response to the nontuberculous mycobacteria, not a primary infection. The treatment, as in this case, is typically just hot tub avoidance. Conclusion: To our knowledge, this is the first case of NTM-HP reported from Wisconsin. NTM-HP can mimic nontuberculous mycobacterial disease and should be on the differential diagnosis for patients with unclear chronic respiratory problems.
MeSH term(s)	Biopsy ; Diagnosis, Differential ; Humans ; Lung/pathology ; Middle Aged ; Mycobacterium Infections, Nontuberculous/diagnosis ; Mycobacterium Infections, Nontuberculous/drug therapy ; Mycobacterium Infections, Nontuberculous/pathology ; Nontuberculous Mycobacteria
Language	English
Publishing date	2022-07-13
Publishing country	United States
Document type	Case Reports ; Review
ZDB-ID	441051-8
ISSN	2379-3961 ; 0043-6542 ; 1098-1861
ISSN (online)	2379-3961
ISSN	0043-6542 ; 1098-1861
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Article ; Online: Rare and complicated functional posterior mediastinal paraganglioma.

SenthilKumar, Gopika / Rokkas, Chris K / Sheinin, Yuri M / Linsky, Paul L

BMJ case reports

2022 Volume 15, Issue 6

Abstract: Functional mediastinal paragangliomas (PGs) are rare, catecholamine-secreting tumours. Surgical resection is the preferred treatment, but it can be complicated by catecholamine-related symptoms, involvement of cardiac structures and/or tumour supply from ...

Abstract	Functional mediastinal paragangliomas (PGs) are rare, catecholamine-secreting tumours. Surgical resection is the preferred treatment, but it can be complicated by catecholamine-related symptoms, involvement of cardiac structures and/or tumour supply from major blood vessels. We report a case of a man in his 30s with a subcarinal functional PG complicated by all three factors. The PG had arterial supplies from the right coronary and bronchial arteries, with mass effect on the left atrium. Given the high risk of intraoperative bleeding, catecholamine surges and injury to right coronary artery, we attempted a minimally invasive strategy that incorporates best practices from the few published cases on functional PGs. We show that a multidisciplinary approach involving alpha/beta blockade, preoperative embolisation of tumour blood supply, robotic-assisted tumour mobilisation and, if needed, open resection with cardiopulmonary bypass can be a safe strategy in the treatment of functional mediastinal paragangliomas adherent to cardiac structures.
MeSH term(s)	Catecholamines ; Humans ; Male ; Mediastinal Neoplasms/diagnostic imaging ; Mediastinal Neoplasms/surgery ; Mediastinum ; Paraganglioma/complications ; Paraganglioma/diagnostic imaging ; Paraganglioma/surgery ; Paraganglioma, Extra-Adrenal
Chemical Substances	Catecholamines
Language	English
Publishing date	2022-06-07
Publishing country	England
Document type	Case Reports ; Journal Article
ISSN	1757-790X
ISSN (online)	1757-790X
DOI	10.1136/bcr-2022-250500
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Article: Tumor Microenvironment-Responsive Polymeric iRGD and Doxorubicin Conjugates Reduce Spontaneous Lung Metastasis in an Orthotopic Breast Cancer Model.

Peng, Zheng-Hong / Jogdeo, Chinmay M / Li, Jing / Xie, Ying / Wang, Yazhe / Sheinin, Yuri M / Kopeček, Jindřich / Oupický, David

Pharmaceutics

2022 Volume 14, Issue 8

Abstract: Tremendous progress has been made in the field of nanomedicine for cancer treatment. However, most of the research to date has been focused on inhibiting primary tumor growth with comparatively less efforts directed towards managing tumor metastasis. ... ...

Abstract	Tremendous progress has been made in the field of nanomedicine for cancer treatment. However, most of the research to date has been focused on inhibiting primary tumor growth with comparatively less efforts directed towards managing tumor metastasis. Here, we introduce a polymeric conjugate P-DOX-iRGD that not only significantly suppressed primary tumor growth but also substantially inhibited pulmonary metastasis in an orthotopic mouse model of breast cancer. In addition, treatment with P-DOX-iRGD markedly reduced breast cancer-induced splenomegaly and liver hematopoiesis. Interestingly, contrasting results were seen for the free form and polymeric form of DOX in vitro and in vivo, which may be attributed to the enhanced permeability and retention (EPR) effect.
Language	English
Publishing date	2022-08-18
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527217-2
ISSN	1999-4923
ISSN	1999-4923
DOI	10.3390/pharmaceutics14081725
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Article ; Online: Diffuse interstitial pneumonia-like/macrophage activation syndrome-like changes in patients with COVID-19 correlate with length of illness.

Felix, Juan C / Sheinin, Yuri M / Suster, David / Ronen, Natali / Ratiani, Mariam / Vanden Heuvel, Tana / Winge, Emilie / Patton, Mollie D / Rau, Mary J / Ge, Linna / Sun, Yunguang / Udhane, Sameer S / Langenheim, John F / Rui, Hallgeir

Annals of diagnostic pathology

2021 Volume 53, Page(s) 151744

Abstract: Objectives: Assess the pathologic changes in the lungs of COVID-19 decedents and correlate these changes with demographic data, clinical course, therapies, and duration of illness.: Methods: Lungs of 12 consecutive COVID-19 decedents consented for ... ...

Abstract	Objectives: Assess the pathologic changes in the lungs of COVID-19 decedents and correlate these changes with demographic data, clinical course, therapies, and duration of illness. Methods: Lungs of 12 consecutive COVID-19 decedents consented for autopsy were evaluated for gross and histopathologic abnormalities. A complete Ghon "en block" dissection was performed on all cases; lung weights and gross characteristics recorded. Immunohistochemical studies were performed to characterize lymphocytic infiltrates and to assess SARS-CoV-2 capsid protein. Results: Two distinct patterns of pulmonary involvement were identified. Three of 12 cases demonstrated a predominance of acute alveolar damage (DAD) while 9 of 12 cases demonstrated a marked increase in intra-alveolar macrophages in a fashion resembling desquamative interstitial pneumonia or macrophage activation syndrome (DIP/MAS). Two patterns were correlated solely with a statistically significant difference in the duration of illness. The group exhibiting DAD had duration of illness of 5.7 days while the group with DIP/MAS had duration of illness of 21.5 days (t-test p = 0.014). Conclusions: The pulmonary pathology of COVID-19 patients demonstrates a biphasic pattern, an acute phase demonstrating DAD changes while the patients with a more prolonged course exhibit a different pattern that resembles DIP/MAS-like pattern. The potential mechanisms and clinical significance are discussed.
MeSH term(s)	Adult ; Aged ; Aged, 80 and over ; Autopsy ; COVID-19/complications ; COVID-19/diagnosis ; COVID-19/pathology ; COVID-19/virology ; Capsid Proteins/metabolism ; Comorbidity ; Female ; Humans ; Immunohistochemistry/methods ; Lung/metabolism ; Lung/pathology ; Lung Diseases, Interstitial/etiology ; Lung Diseases, Interstitial/pathology ; Lung Diseases, Interstitial/virology ; Lymphocytes/metabolism ; Lymphocytes/pathology ; Macrophage Activation Syndrome/etiology ; Macrophage Activation Syndrome/pathology ; Macrophage Activation Syndrome/virology ; Macrophages/pathology ; Male ; Middle Aged ; Pulmonary Alveoli/immunology ; Pulmonary Alveoli/pathology ; SARS-CoV-2/genetics ; Sick Leave
Chemical Substances	Capsid Proteins
Language	English
Publishing date	2021-04-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	1440011-x
ISSN	1532-8198 ; 1092-9134
ISSN (online)	1532-8198
ISSN	1092-9134
DOI	10.1016/j.anndiagpath.2021.151744
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Article ; Online: Loss of N-acetylgalactosaminyltransferase 3 in poorly differentiated pancreatic cancer: augmented aggressiveness and aberrant ErbB family glycosylation.

Chugh, Seema / Meza, Jane / Sheinin, Yuri M / Ponnusamy, Moorthy P / Batra, Surinder K

British journal of cancer

2016 Volume 114, Issue 12, Page(s) 1376–1386

Abstract: Background: Aberrant glycosylation of several proteins underlie pancreatic ductal adenocarcinoma (PDAC) progression and metastasis. O-glycosylation is initiated by a family of enzymes known as polypeptide N-acetylgalactosaminyl transferases (GalNAc-Ts/ ... ...

Abstract	Background: Aberrant glycosylation of several proteins underlie pancreatic ductal adenocarcinoma (PDAC) progression and metastasis. O-glycosylation is initiated by a family of enzymes known as polypeptide N-acetylgalactosaminyl transferases (GalNAc-Ts/GALNTs). In this study, we investigated the role of the O-glycosyltransferase GALNT3 in PDAC. Methods: Immunohistochemistry staining of GALNT3 was performed on normal, inflammatory and neoplastic pancreatic tissues. Several in vitro functional assays such as proliferation, colony formation, migration and tumour-endothelium adhesion assay were conducted in GALNT3 knockdown PDAC cells to investigate its role in disease aggressiveness. Expression of signalling molecules involved in growth and motility was evaluated using western blotting. Effect of GALNT3 knockdown on glycosylation was examined by lectin pull-down assay. Results: N-acetylgalactosaminyl transferase 3 expression is significantly decreased in poorly differentiated PDAC cells and tissues as compared with well/moderately differentiated PDAC. Further, knockdown of GALNT3 resulted in increased expression of poorly differentiated PDAC markers, augmented growth, motility and tumour-endothelium adhesion. Pull-down assay revealed that O-glycans (Tn and T) on EGFR and Her2 were altered in PDAC cells, which was accompanied by their increased phosphorylation. Conclusions: Our study indicates that loss of GALNT3 occurs in poorly differentiated PDAC, which is associated with the increased aggressiveness and altered glycosylation of ErbB family proteins.
MeSH term(s)	Carcinoma, Pancreatic Ductal/enzymology ; Carcinoma, Pancreatic Ductal/metabolism ; Carcinoma, Pancreatic Ductal/pathology ; Cell Differentiation/physiology ; Cell Line, Tumor ; Cell Movement/physiology ; Cell Proliferation/physiology ; Endothelial Cells/pathology ; ErbB Receptors/metabolism ; Gene Knockdown Techniques ; Glycosylation ; Humans ; Immunohistochemistry ; N-Acetylgalactosaminyltransferases/deficiency ; N-Acetylgalactosaminyltransferases/genetics ; N-Acetylgalactosaminyltransferases/metabolism ; Pancreatic Neoplasms/enzymology ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/metabolism ; Pancreatic Neoplasms/pathology ; Phosphorylation ; Polypeptide N-acetylgalactosaminyltransferase
Chemical Substances	N-Acetylgalactosaminyltransferases (EC 2.4.1.-) ; ErbB Receptors (EC 2.7.10.1)
Language	English
Publishing date	2016-05-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	80075-2
ISSN	1532-1827 ; 0007-0920
ISSN (online)	1532-1827
ISSN	0007-0920
DOI	10.1038/bjc.2016.116
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Article ; Online: hPaf1/PD2 interacts with OCT3/4 to promote self-renewal of ovarian cancer stem cells.

Karmakar, Saswati / Seshacharyulu, Parthasarathy / Lakshmanan, Imayavaramban / Vaz, Arokia P / Chugh, Seema / Sheinin, Yuri M / Mahapatra, Sidharth / Batra, Surinder K / Ponnusamy, Moorthy P

Oncotarget

2017 Volume 8, Issue 9, Page(s) 14806–14820

Abstract: Cancer stem cells (CSCs), which mediate drug resistance and disease recurrence in several cancers, are therapeutically relevant to ovarian cancer (OC), wherein approximately 80% of patients manifest with tumor recurrence. While there are several markers ... ...

Abstract	Cancer stem cells (CSCs), which mediate drug resistance and disease recurrence in several cancers, are therapeutically relevant to ovarian cancer (OC), wherein approximately 80% of patients manifest with tumor recurrence. While there are several markers for ovarian CSCs (OCSCs), the mechanism for their self-renewal maintenance by unique driver/markers is poorly understood. Here, we evaluated the role of hPaf1/PD2, a core component of RNA Polymerase II-Associated Factor (PAF) complex, in self-renewal of OCSCs through marker and functional analyses, including CRISPR/Cas9-silencing of hPaf1/PD2 in OCSCs and provided a possible mechanism for maintenance of OCSCs. Expression of hPaf1/PD2 showed moderate to intense staining in 32.4% of human OC tissues, whereas 67.6% demonstrated basal expression by immunohistochemistry analysis, implying that the minor proportion of cells overexpressing hPaf1/PD2 could be putative OCSCs. Isolated OCSCs showed higher expression of hPaf1/PD2 along with established CSC and self-renewal markers. Knockdown of hPaf1/PD2 in OCSCs resulted in a significant downregulation of CSC and self-renewal markers, and impairment of in vitro tumor sphere (P < 0.05) and colony formation (P = 0.013). Co-immunoprecipitation revealed that OCT3/4 specifically interacts with hPaf1/PD2, and not with other PAF components (Ctr9, Leo1, Parafibromin) in OCSCs, suggesting a complex-independent role for hPaf1/PD2 in OCSC maintenance. Moreover, there was a significant overexpression and co-localization of hPaf1/PD2 with OCT3/4 in OC tissues compared to normal ovary tissues. Our results indicate that hPaf1/PD2 is overexpressed in OCSCs and maintains the self-renewal of OCSCs through its interaction with OCT3/4; thus, hPaf1/PD2 may be a potential therapeutic target to overcome tumor relapse in OC.
MeSH term(s)	CRISPR-Cas Systems ; Cell Proliferation ; Female ; Humans ; Neoplasm Staging ; Neoplastic Stem Cells/metabolism ; Neoplastic Stem Cells/pathology ; Nuclear Proteins/antagonists & inhibitors ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Octamer Transcription Factor-3/genetics ; Octamer Transcription Factor-3/metabolism ; Ovarian Neoplasms/genetics ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology ; Prognosis ; Tumor Cells, Cultured
Chemical Substances	Nuclear Proteins ; Octamer Transcription Factor-3 ; PAF1 protein, human ; POU5F1 protein, human
Language	English
Publishing date	2017-02-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.14775
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Article ; Online: Development and characterization of carboxy-terminus specific monoclonal antibodies for understanding MUC16 cleavage in human ovarian cancer.

Aithal, Abhijit / Junker, Wade M / Kshirsagar, Prakash / Das, Srustidhar / Kaur, Sukhwinder / Orzechowski, Catherine / Gautam, Shailendra Kumar / Jahan, Rahat / Sheinin, Yuri M / Lakshmanan, Imayavaramban / Ponnusamy, Moorthy P / Batra, Surinder K / Jain, Maneesh

PloS one

2018 Volume 13, Issue 4, Page(s) e0193907

Abstract: MUC16 is overexpressed in ovarian cancer and plays important roles in invasion and metastasis. Previously described monoclonal antibodies against cell surface expressed MUC16 recognize the N-terminal tandemly repeated epitopes present in cancer antigen ... ...

Abstract	MUC16 is overexpressed in ovarian cancer and plays important roles in invasion and metastasis. Previously described monoclonal antibodies against cell surface expressed MUC16 recognize the N-terminal tandemly repeated epitopes present in cancer antigen 125 (CA125). MUC16 is cleaved at a specific location, thus, releasing CA125 into the extracellular space. Recent reports have indicated that the retained carboxy-terminal (CT) fragment of MUC16 might play an important role in tumorigenicity in diverse types of cancers. However, limited data is available on the fate and existence of CT fragment on the surface of the cancer cell. Herein, we characterize two monoclonal antibodies (mAbs) showing specificity to the retained juxtamembrane region of MUC16. For the first time, we demonstrate that MUC16 is cleaved in ovarian cancer cells (NIH:OVCAR-3 [OVCAR-3]) and that the cleaved MUC16 subunits remain associated with each other. Immunohistochemical analyses on different grades of ovarian tumor tissues indicated differential reactivity of CA125 and MUC16 CT mAbs. The CA125 (M11) mAb detected 32/40 (80%), while the CT mAb (5E6) detected 33/40 (82.5%) of total ovarian cancer cases. For serous and serous papillary cases, the CA125 (M11) mAb stained 27/31 cases (87%), while CT mAb (5E6) stained 29/31 cases (93.5%). The CT mAb(s) accurately predict expression of MUC16 since their epitopes are not tandemly repeated and their reactivity may not be dependent on O-linked glycosylation. These antibodies can serve as valuable reagents for understanding MUC16 cleavage and may also serve as potential therapeutic agents for treatment of ovarian cancer.
MeSH term(s)	Animals ; Antibodies, Monoclonal ; CA-125 Antigen/immunology ; CA-125 Antigen/metabolism ; Cell Line, Tumor ; Epitopes/immunology ; Female ; Humans ; Membrane Proteins/immunology ; Membrane Proteins/metabolism ; Mice ; Mice, Inbred BALB C ; Ovarian Neoplasms/metabolism ; Ovarian Neoplasms/pathology
Chemical Substances	Antibodies, Monoclonal ; CA-125 Antigen ; Epitopes ; MUC16 protein, human ; Membrane Proteins
Language	English
Publishing date	2018-04-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ISSN	1932-6203
ISSN (online)	1932-6203
DOI	10.1371/journal.pone.0193907
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Article ; Online: Crosstalk between PKCα and PI3K/AKT Signaling Is Tumor Suppressive in the Endometrium.

Hsu, Alice H / Lum, Michelle A / Shim, Kang-Sup / Frederick, Peter J / Morrison, Carl D / Chen, Baojiang / Lele, Subodh M / Sheinin, Yuri M / Daikoku, Takiko / Dey, Sudhansu K / Leone, Gustavo / Black, Adrian R / Black, Jennifer D

Cell reports

2018 Volume 24, Issue 3, Page(s) 655–669

Abstract: Protein kinase C (PKC) isozymes are commonly recognized as oncoproteins based on their activation by tumor-promoting phorbol esters. However, accumulating evidence indicates that PKCs can be inhibitory in some cancers, with recent findings propelling a ... ...

Abstract	Protein kinase C (PKC) isozymes are commonly recognized as oncoproteins based on their activation by tumor-promoting phorbol esters. However, accumulating evidence indicates that PKCs can be inhibitory in some cancers, with recent findings propelling a shift in focus to understanding tumor suppressive functions of these enzymes. Here, we report that PKCα acts as a tumor suppressor in PI3K/AKT-driven endometrial cancer. Transcriptional suppression of PKCα is observed in human endometrial tumors in association with aggressive disease and poor prognosis. In murine models, loss of PKCα is rate limiting for endometrial tumor initiation. PKCα tumor suppression involves PP2A-family-dependent inactivation of AKT, which can occur even in the context of genetic hyperactivation of PI3K/AKT signaling by coincident mutations in PTEN, PIK3CA, and/or PIK3R1. Together, our data point to PKCα as a crucial tumor suppressor in the endometrium, with deregulation of a PKCα→PP2A/PP2A-like phosphatase signaling axis contributing to robust AKT activation and enhanced endometrial tumorigenesis.
MeSH term(s)	Animals ; Carcinogenesis/metabolism ; Carcinogenesis/pathology ; Cell Line, Tumor ; Disease Models, Animal ; Endometrial Neoplasms/enzymology ; Endometrial Neoplasms/pathology ; Endometrium/enzymology ; Endometrium/pathology ; Enzyme Activation ; Female ; HEK293 Cells ; Humans ; Mice ; Neoplasm Grading ; Nuclear Proteins/metabolism ; PTEN Phosphohydrolase/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoprotein Phosphatases/metabolism ; Phosphorylation ; Protein Kinase C-alpha/deficiency ; Protein Kinase C-alpha/metabolism ; Protein Phosphatase 2/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction
Chemical Substances	Nuclear Proteins ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Protein Kinase C-alpha (EC 2.7.11.13) ; PHLPP1 protein, mouse (EC 3.1.3.16) ; Phosphoprotein Phosphatases (EC 3.1.3.16) ; Protein Phosphatase 2 (EC 3.1.3.16) ; PTEN Phosphohydrolase (EC 3.1.3.67)
Language	English
Publishing date	2018-08-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2649101-1
ISSN	2211-1247 ; 2211-1247
ISSN (online)	2211-1247
ISSN	2211-1247
DOI	10.1016/j.celrep.2018.06.067
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Article ; Online: B7-H1 expression in malignant pleural mesothelioma is associated with sarcomatoid histology and poor prognosis.

Mansfield, Aaron Scott / Roden, Anja C / Peikert, Tobias / Sheinin, Yuri M / Harrington, Susan M / Krco, Christopher J / Dong, Haidong / Kwon, Eugene D

Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer

2014 Volume 9, Issue 7, Page(s) 1036–1040

Abstract: Introduction: B7 homolog 1 (B7-H1; aka programmed cell death 1 ligand 1) is a negative costimulatory molecule that is associated with poor prognosis in many tumor types. Given the poor prognosis and the limited treatments available for mesothelioma, we ... ...

Abstract	Introduction: B7 homolog 1 (B7-H1; aka programmed cell death 1 ligand 1) is a negative costimulatory molecule that is associated with poor prognosis in many tumor types. Given the poor prognosis and the limited treatments available for mesothelioma, we decided to examine B7-H1 expression and its association with survival in patients with mesothelioma. Methods: Expression of B7-H1 was determined in 106 patients using a mouse monoclonal antihuman B7-H1 (clone 5H1-A3) antibody with immunohistochemistry. Positive expression was defined as ≥5% positively stained cells. Clinicopathologic features and survival were compared between B7-H1-positive and B7-H1-negative groups. Results: Malignant mesotheliomas of 42 patients (40%) expressed B7-H1. Patients with B7-H1-postive tumors were less likely to be offered or undergo therapeutic surgery (p = 0.03). All sarcomatoid mesotheliomas except one desmoplastic subtype expressed B7-H1. Survival was significantly decreased for patients whose tumors expressed B7-H1 (5 months median, 2-9.5 months interquartile range) compared with those whose tumors did not (14.5 months, 9.25-19 months; p < 0.0001). In a multivariate model, B7-H1 expression and sarcomatoid mesothelioma remained significantly associated with worse survival (risk ratio 1.71, 95% confidence interval 1.03-2.78 [p = 0.04] and risk ratio 2.18, 1.08-4.23 [p = 0.03], respectively). Conclusions: B7-H1 is expressed in a substantial proportion of malignant pleural mesotheliomas and is associated with poor survival. Almost all malignant pleural mesotheliomas with sarcomatoid differentiation expressed B7-H1. The expression of B7-H1 may have important therapeutic implications for the management of malignant pleural mesothelioma.
MeSH term(s)	Aged ; B7-H1 Antigen/analysis ; Female ; Humans ; Male ; Mesothelioma/chemistry ; Mesothelioma/pathology ; Middle Aged ; Pleural Neoplasms/chemistry ; Pleural Neoplasms/pathology ; Prognosis ; Survival Rate
Chemical Substances	B7-H1 Antigen ; CD274 protein, human
Language	English
Publishing date	2014-05-09
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2432037-7
ISSN	1556-1380 ; 1556-0864
ISSN (online)	1556-1380
ISSN	1556-0864
DOI	10.1097/JTO.0000000000000177
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Article ; Online: Mucins and associated O-glycans based immunoprofile for stratification of colorectal polyps: clinical implication for improved colon surveillance.

Krishn, Shiv Ram / Kaur, Sukhwinder / Sheinin, Yuri M / Smith, Lynette M / Gautam, Shailendra K / Patel, Asish / Jain, Maneesh / Juvvigunta, Vasthala / Pai, Priya / Lazenby, Audrey J / Roy, Hemant K / Batra, Surinder K

Oncotarget

2017 Volume 8, Issue 4, Page(s) 7025–7038

Abstract: Sessile serrated adenoma/polyps (SSA/P) are premalignant lesions of colorectal cancer that are difficult to distinguish histologically from hyperplastic polyps (HP) of minimal to no malignant potential. Specific markers for differentiating SSA/P from HP ... ...

Abstract	Sessile serrated adenoma/polyps (SSA/P) are premalignant lesions of colorectal cancer that are difficult to distinguish histologically from hyperplastic polyps (HP) of minimal to no malignant potential. Specific markers for differentiating SSA/P from HP can aid clinicians for optimizing colon surveillance intervals. The present study investigates the potential of mucins and associated O-glycans to distinguish SSA/P from HP. Expression of colonic mucins (MUC1, MUC4, MUC17, MUC2, and MUC5AC) and O-glycans [Sialyl LewisA (CA19-9) and Tn/Sialyl-Tn on MUC1] were analyzed in HP (n=33), SSA/P (n=39), and tubular adenoma (TA) (n=36) samples by immunohistochemistry. A significantly reduced expression of MUC4 (p=0.0066), elevated expression of MUC17 (p=0.0002), and MUC5AC (p<0.0001) was observed in SSA/P cases in comparison to HP cases. Interestingly, significantly higher number of SSA/P cases (p<0.0001) exhibited MUC5AC expression in the goblet cells as well as filled the crypt lumen compared to only goblet cells in majority of the HP cases. Improved diagnostic potential was revealed by multivariate logistic regression analysis where combinatorial panel of MUC5AC/MUC17 discriminated SSA/P from HP (SN/SP=85/82%). Finally, the decision tree model based marker panel (CA19-9/MUC17/MUC5AC) predicted HP, SSA/P and TA with SN/SP of 58%/95%, 79%/90% and 97%/83%, respectively. Overall, the mucin and associated O-glycan based panel defined in the present study could aid in discriminating SSA/P from HP to devise better colon surveillance strategies.
Language	English
Publishing date	2017-01-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2560162-3
ISSN	1949-2553 ; 1949-2553
ISSN (online)	1949-2553
ISSN	1949-2553
DOI	10.18632/oncotarget.12347
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