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Article: mRNA Localization and Local Translation of the Microtubule Severing Enzyme, Fidgetin-Like 2, in Polarization, Migration and Outgrowth.

Birnbaum, Rayna / Biswas, Jeetayu / Singer, Robert H / Sharp, David J

bioRxiv : the preprint server for biology

2023

Abstract: Cell motility requires strict spatiotemporal control of protein expression. During cell migration, mRNA localization and local translation in subcellular areas like the leading edge and protrusions are particularly advantageous for regulating the ... ...

Abstract	Cell motility requires strict spatiotemporal control of protein expression. During cell migration, mRNA localization and local translation in subcellular areas like the leading edge and protrusions are particularly advantageous for regulating the reorganization of the cytoskeleton. Fidgetin-Like 2 (FL2), a microtubule severing enzyme (MSE) that restricts migration and outgrowth, localizes to the leading edge of protrusions where it severs dynamic microtubules. FL2 is primarily expressed during development but in adulthood, is spatially upregulated at the leading edge minutes after injury. Here, we show mRNA localization and local translation in protrusions of polarized cells are responsible for FL2 leading edge expression after injury. The data suggests that the RNA binding protein IMP1 is involved in the translational regulation and stabilization of FL2 mRNA, in competition with the miRNA let-7. These data exemplify the role of local translation in microtubule network reorganization during migration and elucidate an unexplored MSE protein localization mechanism.
Language	English
Publishing date	2023-04-17
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.04.17.537087
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Article ; Online: Theranostic Targeting of CUB Domain Containing Protein 1 (CDCP1) in Pancreatic Cancer-Letter.

Birnbaum, David J / Finetti, Pascal / Birnbaum, Daniel / Bertucci, François

Clinical cancer research : an official journal of the American Association for Cancer Research

2020 Volume 26, Issue 20, Page(s) 5539

MeSH term(s)	Antibodies/genetics ; Antibodies/therapeutic use ; Antigens, Neoplasm/genetics ; Cell Adhesion Molecules/antagonists & inhibitors ; Cell Adhesion Molecules/genetics ; Cell Line, Tumor ; Disease-Free Survival ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Molecular Targeted Therapy ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/immunology ; Pancreatic Neoplasms/pathology
Chemical Substances	Antibodies ; Antigens, Neoplasm ; CDCP1 protein, human ; Cell Adhesion Molecules
Language	English
Publishing date	2020-10-13
Publishing country	United States
Document type	Letter
ZDB-ID	1225457-5
ISSN	1557-3265 ; 1078-0432
ISSN (online)	1557-3265
ISSN	1078-0432
DOI	10.1158/1078-0432.CCR-20-1969
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Zs.A 4223: Show issues

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Article ; Online: The aetiology and molecular landscape of insulin resistance.

James, David E / Stöckli, Jacqueline / Birnbaum, Morris J

Nature reviews. Molecular cell biology

2021 Volume 22, Issue 11, Page(s) 751–771

Abstract: Insulin resistance, defined as a defect in insulin-mediated control of glucose metabolism in tissues - prominently in muscle, fat and liver - is one of the earliest manifestations of a constellation of human diseases that includes type 2 diabetes and ... ...

Abstract	Insulin resistance, defined as a defect in insulin-mediated control of glucose metabolism in tissues - prominently in muscle, fat and liver - is one of the earliest manifestations of a constellation of human diseases that includes type 2 diabetes and cardiovascular disease. These diseases are typically associated with intertwined metabolic abnormalities, including obesity, hyperinsulinaemia, hyperglycaemia and hyperlipidaemia. Insulin resistance is caused by a combination of genetic and environmental factors. Recent genetic and biochemical studies suggest a key role for adipose tissue in the development of insulin resistance, potentially by releasing lipids and other circulating factors that promote insulin resistance in other organs. These extracellular factors perturb the intracellular concentration of a range of intermediates, including ceramide and other lipids, leading to defects in responsiveness of cells to insulin. Such intermediates may cause insulin resistance by inhibiting one or more of the proximal components in the signalling cascade downstream of insulin (insulin receptor, insulin receptor substrate (IRS) proteins or AKT). However, there is now evidence to support the view that insulin resistance is a heterogeneous disorder that may variably arise in a range of metabolic tissues and that the mechanism for this effect likely involves a unified insulin resistance pathway that affects a distal step in the insulin action pathway that is more closely linked to the terminal biological response. Identifying these targets is of major importance, as it will reveal potential new targets for treatments of diseases associated with insulin resistance.
MeSH term(s)	Antigens, CD/genetics ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/pathology ; Glucose/genetics ; Glucose/metabolism ; Humans ; Insulin/genetics ; Insulin/metabolism ; Insulin Resistance/genetics ; Liver/metabolism ; Liver/pathology ; Muscle, Skeletal/metabolism ; Muscle, Skeletal/pathology ; Obesity/genetics ; Obesity/metabolism ; Obesity/pathology ; Proto-Oncogene Proteins c-akt/genetics ; Receptor, Insulin/genetics ; Signal Transduction/genetics
Chemical Substances	Antigens, CD ; Insulin ; INSR protein, human (EC 2.7.10.1) ; Receptor, Insulin (EC 2.7.10.1) ; Proto-Oncogene Proteins c-akt (EC 2.7.11.1) ; Glucose (IY9XDZ35W2)
Language	English
Publishing date	2021-07-20
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2031313-5
ISSN	1471-0080 ; 1471-0072
ISSN (online)	1471-0080
ISSN	1471-0072
DOI	10.1038/s41580-021-00390-6
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Zs.A 5446: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MG 26: Show issues

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Article ; Online: 3D-on-2D: A Physiologically Relevant and Gel-Free In Vitro Coculture Method to Assay Antimetastatic Agents.

Dey, Abhinav / Eisenberg, Samuel / Birnbaum, Rayna / Sharp, David J

Methods in molecular biology (Clifton, N.J.)

2022 Volume 2423, Page(s) 103–107

Abstract: Metastasis of cancer cells leads to 90% of lethality among cancer patients. A crucial step in the hematogenous spread of metastatic cancer is the detachment of cells from the primary tumor followed by invasion through nearby blood vessels (Wong and Hynes. ...

Abstract	Metastasis of cancer cells leads to 90% of lethality among cancer patients. A crucial step in the hematogenous spread of metastatic cancer is the detachment of cells from the primary tumor followed by invasion through nearby blood vessels (Wong and Hynes. Cell Cycle 5(8):812-817, 2006). This is common to several solid tumors, including medulloblastoma (Van Ommeren et al. Brain Pathol 30:691-702, 2020). Because invasion is a crucial step in metastasis, the development of assays studying invasion are important for identifying antimetastatic drugs. There is always a need to develop better 3D in vitro models that not only mimic the complexity of in vivo architecture of solid tumors and their microenvironment, but are also simple to execute in medium to high throughput. We developed an in vitro coculture invasion assay that relies on the binary interaction between cancer cells and endothelial cells for research on tumor invasion and antimetastatic drug discovery. The goal of the current protocol is to use the simplicity of a two-dimensional endothelial cell culture to create a gel-free physiological substratum that can facilitate cancer cell invasion from a 3D cancer spheroid. This provides a simple and reproducible biomimetic 3D cell-based system for the analysis of invasion capacity in large populations of tumor spheroids. Using this assay, we can compare the effect of invasion inhibitors/activators on cancer spheroids. The results are analyzed by manual scoring of images for the presence or absence of sprouting from cancer spheroids. This enables simple and fast analysis of metastasis, which facilitates multiparameter examination.
MeSH term(s)	Antineoplastic Agents/pharmacology ; Cell Culture Techniques/methods ; Cell Line, Tumor ; Coculture Techniques ; Endothelial Cells ; Humans ; Spheroids, Cellular
Chemical Substances	Antineoplastic Agents
Language	English
Publishing date	2022-01-03
Publishing country	United States
Document type	Journal Article
ISSN	1940-6029
ISSN (online)	1940-6029
DOI	10.1007/978-1-0716-1952-0_10
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Article ; Online: Low cholesterol biosynthesis favors epithelial-to-mesenchymal transition maintenance and influences tumor molecular subtyping and disease-free survival in colon cancer patients.

Aulas, Anaïs / Liberatoscioli, Maria Lucia / Finetti, Pascal / Cabaud, Olivier / Birnbaum, David J / Usclade, Lucas / Birnbaum, Daniel / Bertucci, François / Mamessier, Emilie

Cancer communications (London, England)

2022 Volume 42, Issue 8, Page(s) 793–797

MeSH term(s)	Cholesterol ; Colonic Neoplasms/genetics ; Colonic Neoplasms/pathology ; Disease-Free Survival ; Epithelial-Mesenchymal Transition ; Humans
Chemical Substances	Cholesterol (97C5T2UQ7J)
Language	English
Publishing date	2022-06-30
Publishing country	United States
Document type	Letter
ISSN	2523-3548
ISSN (online)	2523-3548
DOI	10.1002/cac2.12329
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Article: Analyzing the Effects of Demographic Differences on Patient Outcomes Following Non-pyogenic Intracranial Venous Thrombosis.

Labagnara, Kevin F / Birnbaum, Jessie / Unda, Santiago R / Altschul, David J

Cureus

2021 Volume 13, Issue 11, Page(s) e19753

Abstract: Objective: To investigate the effect of racial and demographic differences on the short-term outcome of patients following a non-pyogenic cerebral venous thrombosis.: Methods: Data from the National Inpatient Sample were gathered from the years 2013 ... ...

Abstract	Objective: To investigate the effect of racial and demographic differences on the short-term outcome of patients following a non-pyogenic cerebral venous thrombosis. Methods: Data from the National Inpatient Sample were gathered from the years 2013 to 2016. Patients who had a non-pyogenic cerebral venous thrombosis were identified. Admissions of patients between different racial groups were compared. Outcome measures included inpatient mortality, length of stay (LOS), all patients refined diagnosis-related group (APR-DRG) severity and mortality risk scores, non-routine discharges, total charges, sepsis, and urinary tract infections (UTIs). Results: We identified 973 patients who were admitted with a non-pyogenic cerebral venous thrombosis between 2013 and 2016. Of those, 65.7% were classified as White, 15.6% as Black, 14.1% as Hispanic, and 4.6% as Asian or Pacific Islander. Compared to White patients, Black patients were found to have a higher severity score upon admission (2.94 ± 0.818 vs 2.77 ± 0.839; p = 0.025) as well as a longer adjusted LOS (8.085 ± 5.917 vs 6.503 ± 5.552; p = 0.004) and log LOS (0.934 ± 0.507 vs 0.773 ± 0.521; p = 0.001). On initial analysis, we found that older age, elevated WBC count, income group, anemia, and an expected primary payer of Medicare/Medicaid were significantly associated with Black race and also worse outcomes. When controlling for these variables using multivariate regression, older age, lower income group, and elevated WBC count were not significantly associated with any measures of outcome. The race was no longer associated with a higher APR-DRG severity score but was still significant for adjusted LOS (p = 0.001) and adjusted log LOS (p = 0.004). Lastly, we noted that anemia and the expected primary payer of Medicare/Medicaid were both independently and significantly associated with APR-DRG severity score (p = 0.003; p = 0.010) and the adjusted log LOS (p = 0.019; p = 0.035). Conclusions: Black patients admitted with a non-pyogenic intracranial venous thrombosis have significantly longer LOS compared to White patients. Anemia and Medicare/Medicaid as the primary expected payer also seem to play a role in longer LOS, as well as the severity of the case.
Language	English
Publishing date	2021-11-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	2747273-5
ISSN	2168-8184
ISSN	2168-8184
DOI	10.7759/cureus.19753
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Article ; Online: The European Union Ban on Microplastics Includes Artificial Turf Crumb Rubber Infill: Other Nations Should Follow Suit.

Zuccaro, Philip / Thompson, David C / de Boer, Jacob / Llompart, Maria / Watterson, Andrew / Bilott, Robert / Birnbaum, Linda S / Vasiliou, Vasilis

Environmental science & technology

2024 Volume 58, Issue 6, Page(s) 2591–2594

MeSH term(s)	Rubber ; Microplastics ; Plastics ; European Union ; Environmental Exposure/analysis
Chemical Substances	Rubber (9006-04-6) ; Microplastics ; Plastics
Language	English
Publishing date	2024-02-01
Publishing country	United States
Document type	Journal Article
ISSN	1520-5851
ISSN (online)	1520-5851
DOI	10.1021/acs.est.4c00047
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Article: CMTM6 stabilizes PD-L1 expression and refines its prognostic value in tumors.

Mamessier, Emilie / Birnbaum, David J / Finetti, Pascal / Birnbaum, Daniel / Bertucci, François

Annals of translational medicine

2017 Volume 6, Issue 3, Page(s) 54

Language	English
Publishing date	2017-12-18
Publishing country	China
Document type	Editorial ; Comment
ZDB-ID	2893931-1
ISSN	2305-5847 ; 2305-5839
ISSN (online)	2305-5847
ISSN	2305-5839
DOI	10.21037/atm.2017.11.26
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Article: Molecular classification as prognostic factor and guide for treatment decision of pancreatic cancer.

Birnbaum, David J / Bertucci, François / Finetti, Pascal / Birnbaum, Daniel / Mamessier, Emilie

Biochimica et biophysica acta. Reviews on cancer

2018 Volume 1869, Issue 2, Page(s) 248–255

Abstract: Clinico-pathological factors fail to consistently predict the outcome after pancreatic resection for pancreatic ductal adenocarcinoma (PDAC). PDACs show a high level of inter- and intra- tumor genetic heterogeneity. A molecular classification should help ...

Abstract	Clinico-pathological factors fail to consistently predict the outcome after pancreatic resection for pancreatic ductal adenocarcinoma (PDAC). PDACs show a high level of inter- and intra- tumor genetic heterogeneity. A molecular classification should help sort patients into less heterogeneous and more appropriate groups regarding the metastatic risk and the therapeutic response, with the consequences of better predicting evolution and better orienting the treatment. PDAC can be classified based on mutational subtypes and 18gene alterations. Whole-genome sequencing identified mutational signatures, mutational burden and hyper-mutated tumors with specific DNA repair defects. Their overlap/similarities allow the definition of molecular subtypes. DNA and RNA classifications can be used in prognosis assessment. They are useful in therapeutic choice for they allow the design of approaches that can predict the respective drug sensitivity of each molecular subtype. This review provides a comprehensive analysis of available molecular classifications in PDAC and how this can help guide clinical decisions.
MeSH term(s)	Animals ; Antineoplastic Agents/therapeutic use ; Biomarkers, Tumor/metabolism ; Carcinoma, Pancreatic Ductal/classification ; Carcinoma, Pancreatic Ductal/drug therapy ; Carcinoma, Pancreatic Ductal/genetics ; Carcinoma, Pancreatic Ductal/pathology ; Clinical Decision-Making ; DNA Mutational Analysis ; Gene Expression Profiling ; Gene Expression Regulation ; Genetic Heterogeneity ; Genetic Predisposition to Disease ; Humans ; Molecular Diagnostic Techniques ; Molecular Targeted Therapy ; Mutation ; Pancreatic Neoplasms/classification ; Pancreatic Neoplasms/drug therapy ; Pancreatic Neoplasms/genetics ; Pancreatic Neoplasms/pathology ; Phenotype ; Precision Medicine ; Predictive Value of Tests ; Transcriptome
Chemical Substances	Antineoplastic Agents ; Biomarkers, Tumor
Language	English
Publishing date	2018-02-28
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	60-7
ISSN	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650 ; 0304-419X ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 1570-9639 ; 0925-4439 ; 1874-9399
ISSN (online)	1879-2596 ; 1879-260X ; 1872-8006 ; 1879-2642 ; 1879-2618 ; 1879-2650
ISSN	0304-419X ; 0006-3002 ; 0005-2728 ; 0005-2736 ; 0304-4165 ; 0167-4838 ; 1388-1981 ; 0167-4889 ; 0167-4781 ; 1570-9639 ; 0925-4439 ; 1874-9399
DOI	10.1016/j.bbcan.2018.02.001
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Uc I Zs.247: Show issues

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Article ; Online: Peripheral Monocytosis at Admission to Predict Cerebral Infarct and Poor Functional Outcomes in Subarachnoid Hemorrhage Patients.

Unda, Santiago R / Birnbaum, Jessie / Labagnara, Kevin / Wong, Megan / Vaishnav, Dhrumil P / Altschul, David J

World neurosurgery

2020 Volume 138, Page(s) e523–e529

Abstract: Objective: Increasing evidence points monocytes' role to be larger than thought in developing cerebral infarction (CI) after subarachnoid hemorrhage (SAH). However, there is no clinical evidence of the relationship between peripheral monocytes and CI ... ...

Abstract	Objective: Increasing evidence points monocytes' role to be larger than thought in developing cerebral infarction (CI) after subarachnoid hemorrhage (SAH). However, there is no clinical evidence of the relationship between peripheral monocytes and CI and clinical outcomes. Therefore we determine whether an increase in monocytes in the acute phase is useful to predict CI and functional outcomes in SAH patients. Methods: We included 204 patients with an SAH diagnosis. We collected patient-related factors, comorbidities, Hunt-Hess grade, modified Fisher grade, treatment, delayed cerebral ischemia, CI, aneurysm characteristics, and peripheral monocytes from vein blood at admission. Poor outcomes were defined as modified Rankin Scale score ≥3. Results: Fifty (24.5%) patients had CI before discharge. In a multivariate model, increased monocytes at admission were significantly associated with CI after adjusting for IV-V Hunt-Hess grade and delayed cerebral ischemia (odds ratio: 3.193, 95% confidence interval: 1.069-9.532, P = 0.037). In receiver operating characteristic curve analysis, a monocyte count of 0.60 was identified as the best cutoff value to discriminate the development of CI (area under the curve = 0.622, P = 0.010; CI for monocytes <0.60 17.4% vs. CI for monocytes ≥0.60 29.1% P = 0.046). Admission monocytes ≥0.60 predicted poor functional outcomes at discharge (monocytes <0.60 52% vs. monocytes ≥0.60 64.7%) and at 12 months (monocytes <0.60 29.4% vs. monocytes ≥0.60 70.6%). Conclusions: Increased peripheral monocytes at admission is a risk factor for developing CI after SAH. Moreover, short- and long-term poor clinical outcomes were associated with higher monocyte count. Therefore monocytes could be a convenient biomarker for prognosis unfavorable outcomes and a possible target for new therapeutic strategies.
MeSH term(s)	Adult ; Aged ; Cerebral Infarction/blood ; Cerebral Infarction/diagnosis ; Female ; Humans ; Leukocyte Count ; Male ; Middle Aged ; Monocytes ; Prognosis ; Retrospective Studies ; Risk Factors ; Subarachnoid Hemorrhage/blood ; Subarachnoid Hemorrhage/diagnosis ; Treatment Outcome
Language	English
Publishing date	2020-03-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	2534351-8
ISSN	1878-8769 ; 1878-8750
ISSN (online)	1878-8769
ISSN	1878-8750
DOI	10.1016/j.wneu.2020.02.170
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