LIVIVO - Search results -

Search results

Result 1 - 10 of total 38

Search options

Article ; Online: Technical feasibility of novel immunostimulatory low-dose radiation for polymetastatic disease with CBCT-based online adaptive and conventional approaches.

Nasser, Nour / Perez, Bradford A / Penagaricano, Jose A / Caudell, Jimmy J / Oliver, Daniel E / Latifi, Kujtim / Moros, Eduardo G / Redler, Gage

Journal of applied clinical medical physics

2024 , Page(s) e14303

Abstract: Purpose: A workflow/planning strategy delivering low-dose radiation therapy (LDRT) (1 Gy) to all polymetastatic diseases using conventional planning/delivery (Raystation/Halcyon = "conventional") and the AI-based Ethos online adaptive RT (oART) platform ...

Abstract	Purpose: A workflow/planning strategy delivering low-dose radiation therapy (LDRT) (1 Gy) to all polymetastatic diseases using conventional planning/delivery (Raystation/Halcyon = "conventional") and the AI-based Ethos online adaptive RT (oART) platform is developed/evaluated. Methods: Using retrospective data for ten polymetastatic non-small cell lung cancer patients (5-52 lesions each) with PET/CTs, gross tumor volumes (GTVs) were delineated using PET standardized-uptake-value (SUV) thresholding. A 1 cm uniform expansion of GTVs to account for setup/contour uncertainty and organ motion-generated planning target volumes (PTVs). Dose optimization/calculation used the diagnostic CT from PET/CT. Dosimetric objectives were: D Results: All initial plans generated, both for Raystation and Ethos, achieved clinical goals within acceptable variation. For all patients, D Conclusions: This study demonstrates feasibility of conventional planning/treatment with Raystation/Halcyon and highlights efficiency gains when utilizing semi-automated planning/online-adaptive treatment with Ethos for immunostimulatory LDRT conformally delivered to all sites of polymetastatic disease.
Language	English
Publishing date	2024-02-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	2010347-5
ISSN	1526-9914 ; 1526-9914
ISSN (online)	1526-9914
ISSN	1526-9914
DOI	10.1002/acm2.14303
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

This service is chargeable due to the Delivery terms set by subito. Orders including an article and supplementary material will be classified as separate orders. In these cases, fees will be demanded for each order.

Article ; Online: Methodology for computed tomography characterization of commercially available 3D printing materials for use in radiology/radiation oncology.

Kozee, Madison / Weygand, Joseph / Andreozzi, Jacqueline M / Hunt, Dylan / Perez, Bradford A / Graham, Jasmine A / Redler, Gage

Journal of applied clinical medical physics

2023 Volume 24, Issue 6, Page(s) e13999

Abstract: 3D printing in medical physics provides opportunities for creating patient-specific treatment devices and in-house fabrication of imaging/dosimetry phantoms. This study characterizes several commercial fused deposition 3D printing materials with some ... ...

Abstract	3D printing in medical physics provides opportunities for creating patient-specific treatment devices and in-house fabrication of imaging/dosimetry phantoms. This study characterizes several commercial fused deposition 3D printing materials with some containing nonstandard compositions. It is important to explore their similarities to human tissues and other materials encountered in patients. Uniform cylinders with infill from 50 to 100% at six evenly distributed intervals were printed using 13 different filaments. A novel approach rotating infill angle 10
MeSH term(s)	Humans ; Radiation Oncology ; Tomography, X-Ray Computed/methods ; Radiography ; Printing, Three-Dimensional ; Radiometry ; Phantoms, Imaging
Language	English
Publishing date	2023-04-24
Publishing country	United States
Document type	Journal Article
ZDB-ID	2010347-5
ISSN	1526-9914 ; 1526-9914
ISSN (online)	1526-9914
ISSN	1526-9914
DOI	10.1002/acm2.13999
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Deep Learning-Guided Dosimetry for Mitigating Local Failure of Patients With Non-Small Cell Lung Cancer Receiving Stereotactic Body Radiation Therapy.

Dudas, Denis / Saghand, Paymen Ghasemi / Dilling, Thomas J / Perez, Bradford A / Rosenberg, Stephen A / El Naqa, Issam

International journal of radiation oncology, biology, physics

2023

Abstract: Purpose: Non-small cell lung cancer (NSCLC) stereotactic body radiation therapy with 50 Gy/5 fractions is sometimes considered controversial, as the nominal biologically effective dose (BED) of 100 Gy is felt by some to be insufficient for long-term ... ...

Abstract	Purpose: Non-small cell lung cancer (NSCLC) stereotactic body radiation therapy with 50 Gy/5 fractions is sometimes considered controversial, as the nominal biologically effective dose (BED) of 100 Gy is felt by some to be insufficient for long-term local control of some lesions. In this study, we analyzed such patients using explainable deep learning techniques and consequently proposed appropriate treatment planning criteria. These novel criteria could help planners achieve optimized treatment plans for maximal local control. Methods and materials: A total of 535 patients treated with 50 Gy/5 fractions were used to develop a novel deep learning local response model. A multimodality approach, incorporating computed tomography images, 3-dimensional dose distribution, and patient demographics, combined with a discrete-time survival model, was applied to predict time to failure and the probability of local control. Subsequently, an integrated gradient-weighted class activation mapping method was used to identify the most significant dose-volume metrics predictive of local failure and their optimal cut-points. Results: The model was cross-validated, showing an acceptable performance (c-index: 0.72, 95% CI, 0.68-0.75); the testing c-index was 0.69. The model's spatial attention was concentrated mostly in the tumors' periphery (planning target volume [PTV] - internal gross target volume [IGTV]) region. Statistically significant dose-volume metrics in improved local control were BED D Conclusions: Deep learning-identified dose-volume metrics have shown significant prognostic power (log-rank, P = .003) and could be used as additional actionable criteria for treatment planning in NSCLC stereotactic body radiation therapy patients receiving 50 Gy in 5 fractions. Although our data do not confirm or refute that a significantly higher BED for the prescription dose is necessary for tumor control in NSCLC, it might be clinically effective to escalate the nominal prescribed dose from BED 100 to 105 Gy.
Language	English
Publishing date	2023-12-05
Publishing country	United States
Document type	Journal Article
ZDB-ID	197614-x
ISSN	1879-355X ; 0360-3016
ISSN (online)	1879-355X
ISSN	0360-3016
DOI	10.1016/j.ijrobp.2023.11.059
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 1218: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article: Inhibitors Targeting CDK9 Show High Efficacy against Osimertinib and AMG510 Resistant Lung Adenocarcinoma Cells.

Padmanabhan, Jaya / Saha, Biswarup / Powell, Chase / Mo, Qianxing / Perez, Bradford A / Chellappan, Srikumar

Cancers

2021 Volume 13, Issue 15

Abstract: Non-small cell lung cancer has a 5-year survival rate of less than 12-15%, calling for the development of additional therapeutic strategies to combat this disease. Here we tested the efficacy of inhibiting cyclin-dependent kinase 9 (CDK9) on lung cancer ... ...

Abstract	Non-small cell lung cancer has a 5-year survival rate of less than 12-15%, calling for the development of additional therapeutic strategies to combat this disease. Here we tested the efficacy of inhibiting cyclin-dependent kinase 9 (CDK9) on lung cancer cell lines with K-Ras and EGFR mutations and on lung cancer organoids. Three different CDK9 inhibitors reduced the viability and anchorage-independent growth of lung cancer cell lines at very low nanomolar to micromolar concentrations. CDK9 inhibition suppressed the expression of the anti-apoptotic protein, Mcl1, as well as the embryonic stem cell transcription factors, Sox2 and Sox9, which are pro-tumorigenic. In contrast, treatment with CDK9 inhibitors increased the levels of WT p53 and its downstream target p21 in K-Ras mutant cell lines. Furthermore, the CDK9 inhibitors could markedly reduce the viability of Osimertinib-resistant PC9 and AMG510-resistant H23 and H358 cells with comparable efficacy as the parental cells. CDK9 inhibitors could also significantly reduce the growth and viability of lung cancer organoids with high potency. Taken together, the data presented here strongly suggest that CDK9 inhibitors would be efficacious against K-Ras mutant and EGFR mutant NSCLCs, including those that develop resistance to targeted therapies.
Language	English
Publishing date	2021-08-03
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers13153906
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Article ; Online: Radiotherapy before and after radical prostatectomy for high-risk and locally advanced prostate cancer.

Perez, Bradford A / Koontz, Bridget F

Urologic oncology

2015 Volume 33, Issue 5, Page(s) 226–234

Abstract: Objectives: Men with localized high-risk prostate cancer carry significant risk of prostate cancer-specific mortality. The best treatment approach to minimize this risk is unclear. In this review, we evaluate the role of radiation before and after ... ...

Abstract	Objectives: Men with localized high-risk prostate cancer carry significant risk of prostate cancer-specific mortality. The best treatment approach to minimize this risk is unclear. In this review, we evaluate the role of radiation before and after radical prostatectomy. Methods and materials: A critical review of the literature was performed regarding the application of external radiation therapy (RT) in combination with prostatectomy for high-risk localized prostate cancer. Results: Up to 70% of men with high-risk localized disease may require adjuvant therapy because of adverse pathologic features or biochemical recurrence in the absence of systemic disease. The utility of adjuvant RT among men with adverse pathologic features are well established at least regarding minimizing biochemical recurrence risk. The optimal timing of salvage radiation is the subject of ongoing studies. Neoadjuvant RT requires further study but is a potentially attractive method because of decreased radiation field sizes and potential radiobiologic benefits of delivering RT before surgery. Salvage prostatectomy is effective at treating local recurrence after radiation but is associated with significant surgical morbidity. Conclusions: Combining local therapies including radical prostatectomy and RT can be a reasonable approach. Care should be taken at the initial presentation of high-risk localized prostate cancer to consider and plan for the likelihood of multimodality care.
MeSH term(s)	Combined Modality Therapy ; Humans ; Male ; Prostatectomy/methods ; Prostatic Neoplasms/pathology ; Prostatic Neoplasms/radiotherapy ; Prostatic Neoplasms/surgery ; Risk
Language	English
Publishing date	2015-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1336505-8
ISSN	1873-2496 ; 1078-1439
ISSN (online)	1873-2496
ISSN	1078-1439
DOI	10.1016/j.urolonc.2014.09.018
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 4817: 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)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Magnetic Resonance-Guided Stereotactic Body Radiation Therapy/Hypofractionated Radiation therapy for Metastatic and Primary Central and Ultracentral Lung Lesions.

Sandoval, Maria L / Sim, Austin J / Bryant, John M / Bhandari, Menal / Wuthrick, Evan J / Perez, Bradford A / Dilling, Thomas J / Redler, Gage / Andreozzi, Jacqueline / Nardella, Louis / Feygelman, Vladimir / Latifi, Kujtim / Rosenberg, Stephen A

JTO clinical and research reports

2023 Volume 4, Issue 5, Page(s) 100488

Abstract: Introduction: The recent results from the Nordic-HILUS study indicate stereotactic body radiation therapy (SBRT) is associated with high-grade toxicity for ultracentral (UC) tumors. We hypothesized that magnetic resonance-guided SBRT (MRgSBRT) or ... ...

Abstract	Introduction: The recent results from the Nordic-HILUS study indicate stereotactic body radiation therapy (SBRT) is associated with high-grade toxicity for ultracentral (UC) tumors. We hypothesized that magnetic resonance-guided SBRT (MRgSBRT) or hypofractionated radiation therapy (MRgHRT) enables the safe delivery of high-dose radiation to central and UC lung lesions. Methods: Patients with UC or central lesions were treated with MRgSBRT/MRgHRT with real-time gating or adaptation. Central lesions were defined as per the Radiation Therapy Oncology Group and UC as per the HILUS study definitions: (1) group A or tumors less than 1 cm from the trachea and/or mainstem bronchi; or (2) group B or tumors less than 1 cm from the lobar bronchi. The Kaplan-Meier estimate and log-rank test were used to estimate survival. Associations between toxicities and other patient factors were tested using the Mann-Whitney Results: A total of 47 patients were included with a median follow-up of 22.9 months (95% confidence interval: 16.4-29.4). Most (53%) had metastatic disease. All patients had central lesions and 55.3% (n = 26) had UC group A. The median distance from the proximal bronchial tree was 6.0 mm (range: 0.0-19.0 mm). The median biologically equivalent dose (α/β = 10) was 105 Gy (range: 75-151.2). The most common radiation schedule was 60 Gy in eight fractions (40.4%). Most (55%) had previous systemic therapy, 32% had immunotherapy and 23.4% had previous thoracic radiation therapy. There were 16 patients who underwent daily adaptation. The 1-year overall survival was 82% (median = not reached), local control 87% (median = not reached), and progression-free survival 54% (median = 15.1 mo, 95% confidence interval: 5.1-25.1). Acute toxicity included grade 1 (26%) and grade 2 (21%) with only two patients experiencing grade 3 (4.3%) in the long term. No grade 4 or 5 toxicities were seen. Conclusions: Previous studies noted high rates of toxicity after SBRT to central and UC lung lesions, with reports of grade 5 toxicities. In our cohort, the use of MRgSBRT/MRgHRT with high biologically effective doses was well tolerated, with two grade 3 toxicities and no grade 4/5.
Language	English
Publishing date	2023-02-25
Publishing country	United States
Document type	Journal Article
ISSN	2666-3643
ISSN (online)	2666-3643
DOI	10.1016/j.jtocrr.2023.100488
Database	MEDical Literature Analysis and Retrieval System OnLINE

Order via subito

Inter-library loan at ZB MED

Your chosen title can be delivered directly to ZB MED Cologne location if you are registered as a user at ZB MED Cologne.

Article ; Online: Combination IFNβ and Membrane-Stable CD40L Maximize Tumor Dendritic Cell Activation and Lymph Node Trafficking to Elicit Systemic T-cell Immunity.

Zheng, Hong / Yu, Xiaoqing / Ibrahim, Mohammed L / Foresman, Dana / Xie, Mengyu / Johnson, Joseph O / Boyle, Theresa A / Ruffell, Brian / Perez, Bradford A / Antonia, Scott J / Ready, Neal / Saltos, Andreas N / Cantwell, Mark J / Beg, Amer A

Cancer immunology research

2023 Volume 11, Issue 4, Page(s) 466–485

Abstract: Oncolytic virus therapies induce the direct killing of tumor cells and activation of conventional dendritic cells (cDC); however, cDC activation has not been optimized with current therapies. We evaluated the adenoviral delivery of engineered membrane- ... ...

Abstract	Oncolytic virus therapies induce the direct killing of tumor cells and activation of conventional dendritic cells (cDC); however, cDC activation has not been optimized with current therapies. We evaluated the adenoviral delivery of engineered membrane-stable CD40L (MEM40) and IFNβ to locally activate cDCs in mouse tumor models. Combined tumor MEM40 and IFNβ expression induced the highest cDC activation coupled with increased lymph node migration, increased systemic antitumor CD8+ T-cell responses, and regression of established tumors in a cDC1-dependent manner. MEM40 + IFNβ combined with checkpoint inhibitors led to effective control of distant tumors and lung metastases. An oncolytic adenovirus (MEM-288) expressing MEM40 + IFNβ in phase I clinical testing induced cancer cell loss concomitant with enhanced T-cell infiltration and increased systemic presence of tumor T-cell clonotypes in non-small cell lung cancer (NSCLC) patients. This approach to simultaneously target two major DC-activating pathways has the potential to significantly affect the solid tumor immunotherapy landscape.
MeSH term(s)	Mice ; Animals ; Carcinoma, Non-Small-Cell Lung ; CD40 Ligand ; Lung Neoplasms ; CD8-Positive T-Lymphocytes ; Dendritic Cells ; Immunotherapy ; Cell Line, Tumor
Chemical Substances	CD40 Ligand (147205-72-9)
Language	English
Publishing date	2023-02-07
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2732489-8
ISSN	2326-6074 ; 2326-6066
ISSN (online)	2326-6074
ISSN	2326-6066
DOI	10.1158/2326-6066.CIR-22-0927
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 7022: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Analysis of Relapse Events After Definitive Chemoradiotherapy in Locally Advanced Non-Small-Cell Lung Cancer Patients.

Grass, G Daniel / Naghavi, Arash O / Abuodeh, Yazan A / Perez, Bradford A / Dilling, Thomas J

Clinical lung cancer

2018 Volume 20, Issue 1, Page(s) e1–e7

Abstract: Background: The appropriate follow-up frequency after definitive chemoradiotherapy (CRT) for locally advanced non-small-cell lung cancer patients is unknown. Although surveillance guidelines have been proposed, very few data support current ... ...

Abstract	Background: The appropriate follow-up frequency after definitive chemoradiotherapy (CRT) for locally advanced non-small-cell lung cancer patients is unknown. Although surveillance guidelines have been proposed, very few data support current recommendations. Here we analyze relapse events after CRT and investigate whether symptomatic relapses versus those detected by surveillance imaging influences outcomes. Patients and methods: Stage III non-small-cell lung cancer patients treated with CRT at our institution between 2005 and 2014 were retrospectively analyzed. Relapse events were grouped into posttreatment intervals and analyzed with cumulative tables. Time to relapse and overall survival (OS) were compared between patients with relapse detection via symptomatic presentation versus surveillance imaging. Results: A total of 211 patients were identified for analysis. The median follow-up was 43 months for patients alive at the time of analysis. The median age was 63 years, and equal proportions had IIIA or IIIB disease. A total of 135 patients (64%) experienced disease relapse, and of these, 74% did so within 12 months. In those who did not experience relapse at ≤ 12 months, 16%, 6%, and < 5% experienced relapse during 12 to 24, 24 to 36, and > 36 months of follow-up, respectively. In patients with relapse, 56% presented symptomatically, which led to inferior median OS compared to those identified by surveillance imaging (23 vs. 36 months; P = .013). Conclusion: This study identified that most relapses occur within 1 year of completing CRT, and approximately half of these occur within 6 months. A symptomatic relapse led to inferior OS. More aggressive surveillance imaging may therefore identify asymptomatic relapses that are amenable to earlier salvage therapy.
MeSH term(s)	Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/epidemiology ; Carcinoma, Non-Small-Cell Lung/mortality ; Chemoradiotherapy ; Cohort Studies ; Female ; Follow-Up Studies ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/epidemiology ; Lung Neoplasms/mortality ; Male ; Middle Aged ; Neoplasm Recurrence, Local/epidemiology ; Neoplasm Staging ; Platinum/therapeutic use ; Retrospective Studies ; Survival Analysis ; United States/epidemiology
Chemical Substances	Platinum (49DFR088MY)
Language	English
Publishing date	2018-08-29
Publishing country	United States
Document type	Journal Article
ZDB-ID	2145146-1
ISSN	1938-0690 ; 1525-7304
ISSN (online)	1938-0690
ISSN	1525-7304
DOI	10.1016/j.cllc.2018.08.009
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Zs.A 5893: 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.MO 440: Show issues

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Clinical outcomes of non-small cell lung cancer brain metastases treated with stereotactic radiosurgery and immune checkpoint inhibitors, EGFR tyrosine kinase inhibitors, chemotherapy and immune checkpoint inhibitors, or chemotherapy alone.

Dohm, Ammoren E / Tang, Joseph D / Mills, Matthew N / Liveringhouse, Casey L / Sandoval, Maria L / Perez, Bradford A / Robinson, Timothy J / Creelan, Benjamin C / Gray, Jhanelle E / Etame, Arnold B / Vogelbaum, Michael A / Forsyth, Peter / Yu, Hsiang-Hsuan Michael / Oliver, Daniel E / Ahmed, Kamran A

Journal of neurosurgery

2022 , Page(s) 1–8

Abstract: Objective: Immune checkpoint inhibitors (ICIs) and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are commonly used in the systemic management of non-small cell lung cancer (NSCLC) brain metastases (BMs). However, optimizing ... ...

Abstract	Objective: Immune checkpoint inhibitors (ICIs) and epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are commonly used in the systemic management of non-small cell lung cancer (NSCLC) brain metastases (BMs). However, optimizing control of NSCLC BM with stereotactic radiosurgery (SRS) and various systemic therapies remains an area of investigation. Methods: Between 2016 and 2019, the authors identified 171 NSCLC BM patients with 646 BMs treated with single-fraction SRS within 3 months of receiving treatment with ICIs (n = 56; 33%), EGFR-TKI (n = 30; 18%), chemotherapy and ICIs (n = 23; 14%), or standard chemotherapy alone (n = 62; 36%). Time-to-event analysis was conducted, and outcomes included distant intracranial control (DIC), local control (LC), and overall survival from SRS. Results: The median follow-up from BM diagnosis was 8.9 months (range 0.3-127 months). The 12-month Kaplan-Meier DIC rates were 37%, 53%, 41%, and 21% (p = 0.047) for the ICI, EGFR-TKI, ICI and chemotherapy, and chemotherapy-alone groups, respectively. On multivariate analysis, DIC was improved with EGFR-TKI (HR 0.4, 95% CI 0.3-0.8, p = 0.005) compared with conventional chemotherapy and treatment with SRS before systemic therapy (HR 0.5, 95% CI 0.3-0.9, p = 0.03) compared with after; and LC was improved with SRS before (HR 0.4, 95% CI 0.2-0.9, p = 0.03) or concurrently (HR 0.3, 95% CI 0.1-0.6, p = 0.003) compared with after. No differences in radionecrosis were noted by timing or type of systemic therapy. Conclusions: The authors' analysis showed significant differences in DIC based on receipt of systemic therapy and treatment with SRS before systemic therapy improved DIC. Prospective evaluation of the potential synergism between systemic therapy and SRS in NSCLC BM management is warranted.
Language	English
Publishing date	2022-11-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	3089-2
ISSN	1933-0693 ; 0022-3085
ISSN (online)	1933-0693
ISSN	0022-3085
DOI	10.3171/2022.9.JNS221896
Database	MEDical Literature Analysis and Retrieval System OnLINE

In stock of ZB MED Cologne/Königswinter

Uk I Zs.135: Show issues

Location:
Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular
ab Jg. 2022: Lesesaal (EG)

Order via subito

Details ▾
- See ZB MED holdings
- Order with fees

Article ; Online: Olfactory Receptor OR2H1 Is an Effective Target for CAR T Cells in Human Epithelial Tumors.

Martin, Alexandra L / Anadon, Carmen M / Biswas, Subir / Mine, Jessica A / Handley, Katelyn F / Payne, Kyle K / Mandal, Gunjan / Chaurio, Ricardo A / Powers, John J / Sprenger, Kimberly B / Rigolizzo, Kristen E / Innamarato, Patrick / Harro, Carly M / Mehta, Sumit / Perez, Bradford A / Wenham, Robert M / Conejo-Garcia, Jose R

Molecular cancer therapeutics

2022 Volume 21, Issue 7, Page(s) 1184–1194

Abstract: Although chimeric antigen receptor (CAR)-expressing T cells have proven success in hematologic malignancies, their effectiveness in solid tumors has been largely unsuccessful thus far. We found that some olfactory receptors are expressed in a variety of ... ...

Abstract	Although chimeric antigen receptor (CAR)-expressing T cells have proven success in hematologic malignancies, their effectiveness in solid tumors has been largely unsuccessful thus far. We found that some olfactory receptors are expressed in a variety of solid tumors of different histologic subtypes, with a limited pattern of expression in normal tissues. Quantification of OR2H1 expression by qRT-PCR and Western blot analysis of 17 normal tissues, 82 ovarian cancers of various histologies, eight non-small cell lung cancers (NSCLCs), and 17 breast cancers demonstrated widespread OR2H1 expression in solid epithelial tumors with expression in normal human tissues limited to the testis. CAR T cells recognizing the extracellular domain of the olfactory receptor OR2H1 were generated with a targeting motif identified through the screening of a phage display library and demonstrated OR2H1-specific cytotoxic killing in vitro and in vivo, using tumor cells with spontaneous expression of variable OR2H1 levels. Importantly, recombinant OR2H1 IgG generated with the VH/VL sequences of the CAR construct specifically detected OR2H1 protein signal in 60 human lung cancers, 40 ovarian carcinomas, and 73 cholangiocarcinomas, at positivity rates comparable with mRNA expression and without OR2H1 staining in 58 normal tissues. CRISPR/Cas9-mediated ablation of OR2H1 confirmed targeting specificity of the CAR and the tumor-promoting role of OR2H1 in glucose metabolism. Therefore, T cells redirected against OR2H1-expressing tumor cells represent a promising therapy against a broad range of epithelial cancers, likely with an admissible toxicity profile.
MeSH term(s)	Female ; Humans ; Cell Line, Tumor ; Immunotherapy, Adoptive ; Lung Neoplasms/genetics ; Lung Neoplasms/therapy ; Neoplasms, Glandular and Epithelial/metabolism ; Ovarian Neoplasms/metabolism ; Receptors, Odorant/metabolism ; T-Lymphocytes
Chemical Substances	Receptors, Odorant ; OR2H1 protein, human
Language	English
Publishing date	2022-05-02
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2063563-1
ISSN	1538-8514 ; 1535-7163
ISSN (online)	1538-8514
ISSN	1535-7163
DOI	10.1158/1535-7163.MCT-21-0872
Database	MEDical Literature Analysis and Retrieval System OnLINE

Full text online

Accessible to users with ZB MED library card

In stock of ZB MED Cologne/Königswinter

Zs.A 5750: 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)

Order via subito

Details ▾

To top

More links

Kategorien

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

Order via subito

Inter-library loan at ZB MED

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito

Full text online

More links

Kategorien

In stock of ZB MED Cologne/Königswinter

Order via subito