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Article ; Online: The Immunobiology of Kidney Cancer.

Drake, Charles G / Stein, Mark N

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2018 , Page(s) JCO2018792648

Abstract: Although kidney cancer (renal cell carcinoma [RCC]) is susceptible to immunotherapy, the immunologic aspects of the tumor microenvironment (TME) in RCC are relatively unique among tumor types. In RCC, baseline CD8 T-cell infiltration is associated with a ...

Abstract	Although kidney cancer (renal cell carcinoma [RCC]) is susceptible to immunotherapy, the immunologic aspects of the tumor microenvironment (TME) in RCC are relatively unique among tumor types. In RCC, baseline CD8 T-cell infiltration is associated with a worse prognosis. In addition, kidney cancer responds to programmed death-1/programmed death-ligand 1 blockade, despite a relatively low tumor mutation burden. Recent clinical data highlight the efficacy of combined immune checkpoint blockade and demonstrate that combining antiangiogenic agents with programmed death-1/programmed death-ligand 1 blockade has additive activity. Yet an important unanswered question in RCC is the nature of the antigens that are targeted by the immune system when immunotherapy is successful. Ongoing clinical studies are interrogating the multiple suppressive mechanisms in the RCC TME, including metabolic pathways such as those mediated by adenosine and tryptophan as well as cytokine-based therapies. Future regimens are likely to be combinatorial and may eventually be based on a broader understanding of the RCC TME and how it is modulated by both conventional and immune-based therapy.
Language	English
Publishing date	2018-10-29
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.2018.79.2648
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Article ; Online: Reply to C.G. Drake.

Stein, Mark N / Jang, Thomas L

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2016 Volume 35, Issue 4, Page(s) 471–472

Language	English
Publishing date	2016-11-21
Publishing country	United States
Document type	Letter ; Comment
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.2016.70.7745
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Article ; Online: Identification of molecularly unique tumor-associated mesenchymal stromal cells in breast cancer patients.

Gordon, Jonathan A R / Evans, Mark F / Ghule, Prachi N / Lee, Kyra / Vacek, Pamela / Sprague, Brian L / Weaver, Donald L / Stein, Gary S / Stein, Janet L

PloS one

2023 Volume 18, Issue 3, Page(s) e0282473

Abstract: The tumor microenvironment is a complex mixture of cell types that bi-directionally interact and influence tumor initiation, progression, recurrence, and patient survival. Mesenchymal stromal cells (MSCs) of the tumor microenvironment engage in crosstalk ...

Abstract	The tumor microenvironment is a complex mixture of cell types that bi-directionally interact and influence tumor initiation, progression, recurrence, and patient survival. Mesenchymal stromal cells (MSCs) of the tumor microenvironment engage in crosstalk with cancer cells to mediate epigenetic control of gene expression. We identified CD90+ MSCs residing in the tumor microenvironment of patients with invasive breast cancer that exhibit a unique gene expression signature. Single-cell transcriptional analysis of these MSCs in tumor-associated stroma identified a distinct subpopulation characterized by increased expression of genes functionally related to extracellular matrix signaling. Blocking the TGFβ pathway reveals that these cells directly contribute to cancer cell proliferation. Our findings provide novel insight into communication between breast cancer cells and MSCs that are consistent with an epithelial to mesenchymal transition and acquisition of competency for compromised control of proliferation, mobility, motility, and phenotype.
MeSH term(s)	Cell Line, Tumor ; Cell Proliferation ; Epithelial-Mesenchymal Transition/genetics ; Mesenchymal Stem Cells/metabolism ; Signal Transduction ; Stromal Cells/metabolism ; Transcriptome ; Tumor Microenvironment/genetics ; Humans ; Breast Neoplasms/diagnosis ; Breast Neoplasms/genetics
Language	English
Publishing date	2023-03-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2267670-3
ISSN	1932-6203 ; 1932-6203
ISSN (online)	1932-6203
ISSN	1932-6203
DOI	10.1371/journal.pone.0282473
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Article ; Online: Striving Toward a Cure for Prostate Cancer.

Stein, Mark N / Jang, Thomas L

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

2016 Volume 34, Issue 18, Page(s) 2075–2078

MeSH term(s)	Humans ; Male ; Prostate-Specific Antigen ; Prostatic Neoplasms
Chemical Substances	Prostate-Specific Antigen (EC 3.4.21.77)
Language	English
Publishing date	2016-03-28
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	604914-x
ISSN	1527-7755 ; 0732-183X
ISSN (online)	1527-7755
ISSN	0732-183X
DOI	10.1200/JCO.2015.66.3146
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Article ; Online: Identification of molecularly unique tumor-associated mesenchymal stromal cells in breast cancer patients.

Jonathan A R Gordon / Mark F Evans / Prachi N Ghule / Kyra Lee / Pamela Vacek / Brian L Sprague / Donald L Weaver / Gary S Stein / Janet L Stein

PLoS ONE, Vol 18, Iss 3, p e

2023 Volume 0282473

Abstract	The tumor microenvironment is a complex mixture of cell types that bi-directionally interact and influence tumor initiation, progression, recurrence, and patient survival. Mesenchymal stromal cells (MSCs) of the tumor microenvironment engage in crosstalk with cancer cells to mediate epigenetic control of gene expression. We identified CD90+ MSCs residing in the tumor microenvironment of patients with invasive breast cancer that exhibit a unique gene expression signature. Single-cell transcriptional analysis of these MSCs in tumor-associated stroma identified a distinct subpopulation characterized by increased expression of genes functionally related to extracellular matrix signaling. Blocking the TGFβ pathway reveals that these cells directly contribute to cancer cell proliferation. Our findings provide novel insight into communication between breast cancer cells and MSCs that are consistent with an epithelial to mesenchymal transition and acquisition of competency for compromised control of proliferation, mobility, motility, and phenotype.
Keywords	Medicine ; R ; Science ; Q
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The Shared Core Resource as a Partner in Innovative Scientific Research: Illustration from an Academic Microscopy Imaging Center.

Taatjes, Douglas J / Ghule, Prachi N / Bouffard, Nicole A / Lee, Kyra / DeLance, Nicole M / Evans, Mark F / Weaver, Donald L / Deakin, Nicholas / Carr, Frances E / Sprague, Brian L / Stein, Gary S / Stein, Janet L

Journal of biomolecular techniques : JBT

2022 Volume 33, Issue 1

Abstract: Core facilities have a ubiquitous and increasingly valuable presence at research institutions. Although many shared cores were originally created to provide routine services and access to complex and expensive instrumentation for the research community, ... ...

Abstract	Core facilities have a ubiquitous and increasingly valuable presence at research institutions. Although many shared cores were originally created to provide routine services and access to complex and expensive instrumentation for the research community, they are frequently called upon by investigators to design protocols and procedures to help answer complex research questions. For instance, shared microscopy resources are evolving from providing access to and training on complex imaging instruments to developing detailed innovative protocols and experimental strategies, including sample preparation techniques, staining, complex imaging parameters, and high-level image analyses. These approaches require close intellectual collaboration between core staff and research investigators to formulate and coordinate plans for protocol development suited to the research question. Herein, we provide an example of such coordinated collaboration between a shared microscopy facility and a team of scientists and clinician-investigators to approach a complex multiprobe immunostaining, imaging, and image analysis project investigating the tumor microenvironment from human breast cancer samples. Our hope is that this example may be used to convey to institute administrators the critical importance of the intellectual contributions of the scientific staff in core facilities to research endeavors.
MeSH term(s)	Academies and Institutes ; Health Facilities ; Humans ; Microscopy ; Research Design ; Research Personnel
Language	English
Publishing date	2022-03-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2116011-9
ISSN	1943-4731 ; 1943-4731
ISSN (online)	1943-4731
ISSN	1943-4731
DOI	10.7171/3fc1f5fe.2507f36c
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Article ; Online: ADXS31142 Immunotherapy ± Pembrolizumab Treatment for Metastatic Castration-Resistant Prostate Cancer: Open-Label Phase I/II KEYNOTE-046 Study.

Stein, Mark N / Fong, Lawrence / Tutrone, Ronald / Mega, Anthony / Lam, Elaine T / Parsi, Megan / Vangala, Surya / Gutierrez, Andres A / Haas, Naomi B

The oncologist

2022 Volume 27, Issue 6, Page(s) 453–461

Abstract: ... alone (n = 13) or with pembrolizumab (n = 37). Among the 37 RECIST-evaluable patients (n = 8 Part A; n ... in combination-treated patients who had received prior docetaxel (16.0 months, 95% CI: 6.4-34.6; n = 20) and ... those with visceral metastasis (16.4 months, 95% CI 4.0-not evaluable; n = 11). All patients had ≥1 treatment-related ...

Abstract	Background: ADXS31-142 is an attenuated Listeria monocytogenes-based immunotherapy targeting prostate-specific antigen (PSA), being evaluated as monotherapy and combined with pembrolizumab for metastatic castration-resistant prostate cancer (mCRPC). Patients and methods: The 2-part phase I/II KEYNOTE-046 study enrolled men with mCRPC who have progressed after 2 or fewer prior systemic treatment regimens in the metastatic setting. In Part A, intravenous ADXS31-142 monotherapy was given every 3 weeks (q3w) to 3 dose-escalation cohorts. In Part B, ADXS31-142 (1 × 109 colony-forming units) plus pembrolizumab (200 mg) was administered intravenously q3w for 3 doses with a fourth pembrolizumab dose 3 weeks later (12-week cycles) for up to 24 months or until progression/toxicity. Endpoints included safety, overall response rate, progression-free survival (PFS), overall survival (OS), and immunogenicity. Results: Fifty patients received ADXS31-142 alone (n = 13) or with pembrolizumab (n = 37). Among the 37 RECIST-evaluable patients (n = 8 Part A; n = 29 Part B), there were no objective responses. Median PFS was 2.2 months (95% CI: 0.8-7.4) with monotherapy and 5.4 months (95% CI: 2.3-7.9) with the combination; median OS was 7.8 months (95% CI: 4.4-18.5) and 33.7 months (95% CI: 15.4-not evaluable), respectively. Promising OS benefit was observed in combination-treated patients who had received prior docetaxel (16.0 months, 95% CI: 6.4-34.6; n = 20) and those with visceral metastasis (16.4 months, 95% CI 4.0-not evaluable; n = 11). All patients had ≥1 treatment-related adverse event, mostly grade 1/2 manageable events. No additive toxicity was observed with combination treatment. Conclusions: Combining ADXS31-142 with pembrolizumab was safe and well tolerated. The observed OS in mCRPC warrants further testing of this combination. Clinical trial registration: NCT02325557.
MeSH term(s)	Antibodies, Monoclonal, Humanized/pharmacology ; Antibodies, Monoclonal, Humanized/therapeutic use ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Docetaxel/therapeutic use ; Humans ; Immunotherapy ; Male ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/pathology
Chemical Substances	Antibodies, Monoclonal, Humanized ; Docetaxel (15H5577CQD) ; pembrolizumab (DPT0O3T46P)
Language	English
Publishing date	2022-03-26
Publishing country	England
Document type	Clinical Trial, Phase I ; Clinical Trial, Phase II ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1409038-7
ISSN	1549-490X ; 1083-7159
ISSN (online)	1549-490X
ISSN	1083-7159
DOI	10.1093/oncolo/oyac048
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Article: Impact of Phosphoproteomics in the Era of Precision Medicine for Prostate Cancer.

Ramroop, Johnny R / Stein, Mark N / Drake, Justin M

Frontiers in oncology

2018 Volume 8, Page(s) 28

Abstract: Prostate cancer is the most common malignancy in men in the United States. While androgen deprivation therapy results in tumor responses initially, there is relapse and progression to metastatic castration-resistant prostate cancer. Currently, all ... ...

Abstract	Prostate cancer is the most common malignancy in men in the United States. While androgen deprivation therapy results in tumor responses initially, there is relapse and progression to metastatic castration-resistant prostate cancer. Currently, all prostate cancer patients receive essentially the same treatment, and there is a need for clinically applicable technologies to provide predictive biomarkers toward personalized therapies. Genomic analyses of tumors are used for clinical applications, but with a paucity of obvious driver mutations in metastatic castration-resistant prostate cancer, other applications, such as phosphoproteomics, may complement this approach. Immunohistochemistry and reverse phase protein arrays are limited by the availability of reliable antibodies and evaluates a preselected number of targets. Mass spectrometry-based phosphoproteomics has been used to profile tumors consisting of thousands of phosphopeptides from individual patients after surgical resection or at autopsy. However, this approach is time consuming, and while a large number of candidate phosphopeptides are obtained for evaluation, limitations are reduced reproducibility, sensitivity, and precision. Targeted mass spectrometry can help eliminate these limitations and is more cost effective and less time consuming making it a practical platform for future clinical testing. In this review, we discuss the use of phosphoproteomics in prostate cancer and other clinical cancer tissues for target identification, hypothesis testing, and possible patient stratification. We highlight the majority of studies that have used phosphoproteomics in prostate cancer tissues and cell lines and propose ways forward to apply this approach in basic and clinical research. Overall, the implementation of phosphoproteomics
Language	English
Publishing date	2018-02-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2649216-7
ISSN	2234-943X
ISSN	2234-943X
DOI	10.3389/fonc.2018.00028
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Article ; Online: Creating ophthalmology experiences in undergraduate medical education: pilot of a cased-based learning ophthalmology tool.

Tran, Jessica H / Loebel, Emma / Edouard, Mark / Quehl, Thomas / Walsh, Erin / Ginsburg, Robin / Frempong, Tameisha / Fredrick, Douglas / Stein, Laura K / Fara, Michael G / Farouk, Samira S / Chadha, Nisha

BMC medical education

2023 Volume 23, Issue 1, Page(s) 559

Abstract: ... Most (n = 21/23, 91.3%) rated the tool as good/excellent. Of 145 neurology clerkship students, 125 (86 ...

Abstract	Purpose: To evaluate medical student perceptions of a novel ophthalmology resource delivered through facilitated workshops in the core clerkship curriculum. Methods: We created www.2020sim.com, a free case-based learning (CBL) ophthalmology tool, adapted from NephSIM (www.nephsim.com). The tool was first piloted with the internal medicine (IM) residents. After confirming a need, we focused on undergraduate medical education (UME) by expanding the 20/20 SIM content and partnering with the neurology (pilot academic year [AY] 2020-2021) and pediatric clerkships (pilot AY 2021-2022) to deliver a facilitated one-hour ophthalmology workshop within each clerkship's didactic curriculum. We evaluated the tool using pre- and post-surveys and knowledge assessments. Results: Of 80 IM residents, 33 (41.3%) completed the needs assessment. Of the 25 residents who attended the workshop, 23 (92.0%) completed the exit survey. IM residents reported discomfort in several ophthalmology domains (9 of 14 rated mean score < 3.0), confirming a need. Most (n = 21/23, 91.3%) rated the tool as good/excellent. Of 145 neurology clerkship students, 125 (86.2%) and at least 88 (60.7%) students completed the pre- and post-test/exit surveys, respectively. On average, participants highly rated the tool, perceiving 20/20 SIM to be relevant to their education [4.1 (0.8)]. Mean pre- to post-test knowledge scores increased from 7.5 to 8.5/10.0 points (p < 0.001). Of the 136 pediatric clerkship students, 67 (49.3%) and 51 (37.5%) completed the pre- and post-surveys, respectively. Respondents perceived increased comfort with ophthalmology topics after the facilitated workshop [3.8 (0.8)]. Mean pre- to post-test knowledge scores trended from 1.8 to 2.0/5.0 points (p = 0.30). Collectively, 20/139 (14.4%) of exit survey respondents visited www.2020sim.com within 1 month after the workshop. Conclusion: After identifying areas of greatest need with residents, we partnered with core clerkships to deliver cross-disciplinary ophthalmology content in UME. We found high engagement with 20/20 SIM, with trends toward increased knowledge.
MeSH term(s)	Humans ; Child ; Education, Medical, Undergraduate ; Ophthalmology ; Clinical Clerkship ; Curriculum ; Students, Medical
Language	English
Publishing date	2023-08-09
Publishing country	England
Document type	Journal Article
ZDB-ID	2044473-4
ISSN	1472-6920 ; 1472-6920
ISSN (online)	1472-6920
ISSN	1472-6920
DOI	10.1186/s12909-023-04514-8
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Article ; Online: Efficacy and safety of roflumilast cream for chronic plaque psoriasis with facial/neck and intertriginous area involvement: a post hoc analysis from a randomized controlled trial.

Draelos, Zoe D / Adam, David N / Hong, H Chih-Ho / Lebwohl, Mark G / Lynde, Charles W / Nahm, Walter K / Papp, Kim A / Pariser, David M / Stein Gold, Linda / Stewart, Daniel / Higham, Robert C / Berk, David R / Krupa, David / Burnett, Patrick

The British journal of dermatology

2023 Volume 188, Issue 6, Page(s) 810–812

MeSH term(s)	Humans ; Psoriasis/drug therapy ; Aminopyridines/adverse effects ; Benzamides ; Emollients ; Treatment Outcome ; Double-Blind Method ; Severity of Illness Index
Chemical Substances	Roflumilast (0P6C6ZOP5U) ; Aminopyridines ; Benzamides ; Emollients
Language	English
Publishing date	2023-03-08
Publishing country	England
Document type	Randomized Controlled Trial ; Journal Article
ZDB-ID	80076-4
ISSN	1365-2133 ; 0007-0963
ISSN (online)	1365-2133
ISSN	0007-0963
DOI	10.1093/bjd/ljad060
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