المؤلفون: Goyal, Lipika, Meric-Bernstam, Funda, Hollebecque, Antoine, Valle, Juan W, Morizane, Chigusa, Karasic, Thomas B, Abrams, Thomas A, Furuse, Junji, Kelley, Robin Katie, Cassier, Philippe A, Klümpen, Heinz-Josef, Chang, Heung-Moon, Chen, Li-Tzong, Tabernero, Josep, Oh, Do-Youn, Mahipal, Amit, Moehler, Markus, Komatsu, Yoshito, Ahn, Daniel H, Epstein, Robert S, Halim, Abdel-Baset, Wacheck, Volker, He, Yaohua, Liu, Mei, Benhadji, Karim A, Bridgewater, John A

المصدر: Future Oncology ; page 1-12 ; ISSN 1479-6694 1744-8301

الإتاحة: https://doi.org/10.1080/14796694.2024.2364504Test

المؤلفون: Kent, Johnathan, Nordgren, Rachel, Ahn, Daniel, Lysandrou, Maria, Diaz, Ashley, Fenton, David, Wignakumar, Thirushan, McMeekin, Nicola, Salerno, Christopher, Donington, Jessica, Madariaga, Maria Lucia L.

المصدر: Artificial Organs ; ISSN 0160-564X 1525-1594

الوصف: Background Portable ex vivo lung perfusion during lung transplantation is a resource‐intensive technology. In light of its increasing use, we evaluated the cost‐effectiveness of ex vivo lung perfusion at a low‐volume lung transplant center in the USA. Methods Patients listed for lung transplantation (2015–2021) in the United Network for Organ Sharing database were included. Quality‐of‐life was approximated by Karnofsky Performance Status scores 1‐year post‐transplant. Total transplantation encounter and 1‐year follow‐up costs accrued by our academic center for patients listed from 2018 to 2021 were obtained. Cost‐effectiveness was calculated by evaluating the number of patients attaining various Karnofsky scores relative to cost. Results Of the 13 930 adult patients who underwent lung transplant in the United Network for Organ Sharing database, 13 477 (96.7%) used static cold storage and 453 (3.3%) used ex vivo lung perfusion, compared to 30/58 (51.7%) and 28/58 (48.3%), respectively, at our center. Compared to static cold storage, median total costs at 1 year were higher for ex vivo lung perfusion ($918 000 vs. $516 000; p = 0.007) along with the cost of living 1 year with a Karnofsky functional status of 100 after transplant ($1 290 000 vs. $841 000). In simulated scenarios, each Karnofsky‐adjusted life year gained by ex vivo lung perfusion was 1.00–1.72 times more expensive. Conclusions Portable ex vivo lung perfusion is not currently cost‐effective at a low‐volume transplant centers in the USA, being 1.53 times more expensive per Karnofsky‐adjusted life year. Improving donor lung and/or recipient biology during ex vivo lung perfusion may improve its utility for routine transplantation.

الإتاحة: https://doi.org/10.1111/aor.14816Test

المؤلفون: Goyal, Lipika, Meric-Bernstam, Funda, Hollebecque, Antoine, Valle, Juan W., Morizane, Chigusa, Karasic, Thomas B., Abrams, Thomas A., Furuse, Junji, Kelley, Robin K., Cassier, Philippe A., Klümpen, Heinz-Josef, Chang, Heung-Moon, Chen, Li-Tzong, Tabernero, Josep, Oh, Do-Youn, Mahipal, Amit, Moehler, Markus, Mitchell, Edith P., Komatsu, Yoshito, Masuda, Kunihiro, Ahn, Daniel, Epstein, Robert S., Halim, Abdel-Baset, Fu, Yao, Salimi, Tehseen, Wacheck, Volker, He, Yaohua, Liu, Mei, Benhadji, Karim A., Bridgewater, John A.

المصدر: Goyal , L , Meric-Bernstam , F , Hollebecque , A , Valle , J W , Morizane , C , Karasic , T B , Abrams , T A , Furuse , J , Kelley , R K , Cassier , P A , Klümpen , H-J , Chang , H-M , Chen , L-T , Tabernero , J , Oh , D-Y , Mahipal , A , Moehler , M , Mitchell , E P , Komatsu , Y , Masuda , K , Ahn , D , Epstein , R S , Halim , A-B , ....

الوصف: Background: Alterations in fibroblast growth factor receptor 2 (FGFR2) have emerged as promising drug targets for intrahepatic cholangiocarcinoma, a rare cancer with a poor prognosis. Futibatinib, a next-generation, covalently binding FGFR1-4 inhibitor, has been shown to have both antitumor activity in patients with FGFR-altered tumors and strong preclinical activity against acquired resistance mutations associated with ATP-competitive FGFR inhibitors. Methods: In this multinational, open-label, single-group, phase 2 study, we enrolled patients with unresectable or metastatic FGFR2 fusion-positive or FGFR2 rearrangement-positive intrahepatic cholangiocarcinoma and disease progression after one or more previous lines of systemic therapy (excluding FGFR inhibitors). The patients received oral futibatinib at a dose of 20 mg once daily in a continuous regimen. The primary end point was objective response (partial or complete response), as assessed by independent central review. Secondary end points included the response duration, progression-free and overall survival, safety, and patient-reported outcomes. Results: Between April 16, 2018, and November 29, 2019, a total of 103 patients were enrolled and received futibatinib. A total of 43 of 103 patients (42%; 95% confidence interval, 32 to 52) had a response, and the median duration of response was 9.7 months. Responses were consistent across patient subgroups, including patients with heavily pretreated disease, older adults, and patients who had co-occurring TP53 mutations. At a median follow-up of 17.1 months, the median progression-free survival was 9.0 months and overall survival was 21.7 months. Common treatment-related grade 3 adverse events were hyperphosphatemia (in 30% of the patients), an increased aspartate aminotransferase level (in 7%), stomatitis (in 6%), and fatigue (in 6%). Treatment-related adverse events led to permanent discontinuation of futibatinib in 2% of the patients. No treatment-related deaths occurred. Quality of life was maintained ...

العلاقة: https://research.vumc.nl/en/publications/cd4cc245-ebdb-4ee6-adae-ae845072be13Test

الإتاحة: https://doi.org/10.1056/NEJMoa2206834Test
https://research.vumc.nl/en/publications/cd4cc245-ebdb-4ee6-adae-ae845072be13Test
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85149023684&origin=inwardTest
https://www.ncbi.nlm.nih.gov/pubmed/36652354Test

المؤلفون: Ou, Fang Shu, Ahn, Daniel H., Dixon, Jesse G., Grothey, Axel, Lou, Yiyue, Kasi, Pashtoon M., Hubbard, Joleen M., Van Cutsem, Eric, Saltz, Leonard B., Schmoll, Hans Joachim, Goldberg, Richard M., Venook, Alan P., Hoff, Paulo, Douillard, Jean Yves, Hecht, J. Randolph, Hurwitz, Herbert, Punt, Cornelis J.A., Koopman, Miriam, Bokemeyer, Carsten, Fuchs, Charles S., Diaz-Rubio, Eduardo, Tebbutt, Niall C., Cremolini, Chiara, Kabbinavar, Fairooz F., Bekaii-Saab, Tanios, Chibaudel, Benoist, Yoshino, Takayuki, Zalcberg, John, Adams, Richard A., de Gramont, Aimery, Shi, Qian

المساهمون: Cancer, Epi Kanker Team B, MS Medische Oncologie

مصطلحات موضوعية: cancer trials, tumor measurement-based endpoints, Oncology, Cancer Research

الوصف: Metastatic colorectal cancer (mCRC) is a heterogeneous disease that can evoke discordant responses to therapy among different lesions in individual patients. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria do not take into consideration response heterogeneity. We explored and developed lesion-based measurement response criteria to evaluate their prognostic effect on overall survival (OS). Patients and Methods: Patients enrolled in 17 first-line clinical trials, who had mCRC with ≥ 2 lesions at baseline, and a restaging scan by 12 weeks were included. For each patient, lesions were categorized as a progressing lesion (PL: > 20% increase in the longest diameter (LD)), responding lesion (RL: > 30% decrease in LD), or stable lesion (SL: neither PL nor RL) based on the 12-week scan. Lesion-based response criteria were defined for each patient as follows: PL only, SL only, RL only, and varied responses (mixture of RL, SL, and PL). Lesion-based response criteria and OS were correlated using stratified multivariable Cox models. The concordance between OS and classifications was measured using the C statistic. Results: Among 10,551 patients with mCRC from 17 first-line studies, varied responses were noted in 51.6% of patients, among whom, 3.3% had RL/PL at 12 weeks. Among patients with RL/SL, 52% had stable disease (SD) by RECIST 1.1, and they had a longer OS (median OS (mOS) = 19.9 months) than those with SL only (mOS = 16.8 months, HR (95% CI) = 0.81 (0.76, 0.85), p < 0.001), although a shorter OS than those with RL only (mOS = 25.8 months, HR (95% CI) = 1.42 (1.32, 1.53), p < 0.001). Among patients with SL/PL, 74% had SD by RECIST 1.1, and they had a longer OS (mOS = 9.0 months) than those with PL only (mOS = 8.0 months, HR (95% CI) = 0.75 (0.57, 0.98), p = 0.040), yet a shorter OS than those with SL only (mOS = 16.8 months, HR (95% CI) = 1.98 (1.80, 2.18), p < 0.001). These associations were consistent across treatment regimen subgroups. The lesion-based response criteria showed ...

وصف الملف: application/pdf

العلاقة: https://dspace.library.uu.nl/handle/1874/450042Test

الإتاحة: https://dspace.library.uu.nl/handle/1874/450042Test

المؤلفون: Johnson, Daniel Y., Ahn, Daniel, Lazenby, Kevin, Zeng, Sharon, Zhang, Kevin, Narang, Nikhil, Khush, Kiran, Parker, William F.

المصدر: The Journal of Heart and Lung Transplantation ; volume 42, issue 9, page 1175-1182 ; ISSN 1053-2498

مصطلحات موضوعية: Transplantation, Cardiology and Cardiovascular Medicine, Pulmonary and Respiratory Medicine, Surgery

الإتاحة: https://doi.org/10.1016/j.healun.2023.05.009Test
https://api.elsevier.com/content/article/PII:S1053249823018636?httpAccept=text/xmlTest
https://api.elsevier.com/content/article/PII:S1053249823018636?httpAccept=text/plainTest

المؤلفون: Desai, Aakash, Xiao, Alexander H., Choi, Daheui, Toruner, Merih D., Walden, Daniel, Halfdanarson, Thorvardur R., Alberts, Steven, McWilliams, Robert R., Mahipal, Amit, Ahn, Daniel, Babiker, Hani, Stybayeva, Gulnaz, Revzin, Alexander, Kizilbash, Sani, Adjei, Alex, Bekaii-Saab, Tanios, Mansfield, Aaron S., Carr, Ryan M., Ma, Wen Wee

المصدر: Cancers; May2024, Vol. 16 Issue 10, p1861, 12p

مصطلحات موضوعية: THERAPEUTIC use of antineoplastic agents, GENOMICS, RESEARCH funding, PROTEIN-tyrosine kinase inhibitors, COMPUTED tomography, TUMOR markers, CANCER patients, FLUORESCENT antibody technique, PANCREATIC tumors, SMALL molecules, GENETIC variation, DUCTAL carcinoma, DRUG efficacy, MEDICAL records, ACQUISITION of data, GENE expression profiling, GENETIC mutation, SEQUENCE analysis, OVERALL survival

مستخلص: Simple Summary: Pancreatic cancer is predicted to be the second-highest cause of cancer mortality in the US by 2040. It is driven by various mutations including KRAS, TP53, SMAD4, and CDKN2A. Roughly 1 in 10 patients with pancreatic cancer have wildtype KRAS (KRAS^WT). We studied 27 patients with KRAS^WT to better understand their molecular characteristics and potential for precision medicine. Our findings revealed that KRAS^WT PDAC is enriched with potentially treatable genetic alterations, including those affecting the MAPK pathway, DNA repair pathway, and kinase fusion genes. One of our KRAS^WT PDAC patients was found to have a specific, targetable TFG-MET mutation and they responded well to treatment with a cMET inhibitor. This suggests that KRAS^WT PDAC has unique genetic characteristics that could be targeted with specific treatments tailored to each patient, highlighting the importance of comprehensive genetic profiling in KRAS^WT PDAC. Purpose: To investigate the molecular characteristics of and potential for precision medicine in KRAS wildtype pancreatic ductal adenocarcinoma (PDAC). Patients and Methods: We investigated 27 patients with KRAS^WT PDAC at our institution. Clinical data were obtained via chart review. Tumor specimens for each subject were interrogated for somatic single nucleotide variants, insertion and deletions, and copy number variants by DNA sequencing. Gene fusions were detected from RNA-seq. A patient-derived organoid (PDO) was developed from a patient with a MET translocation and expanded ex vivo to predict therapeutic sensitivity prior to enrollment in a phase 2 clinical trial. Results: Transcriptomic analysis showed our cohort may be stratified by the relative gene expression of the KRAS signaling cascade. The PDO derived from our patient harboring a TFG-MET rearrangement was found to have in vitro sensitivity to the multi-tyrosine kinase inhibitor crizotinib. The patient was enrolled in the phase 2 SPARTA clinical trial and received monotherapy with vebrelitinib, a c-MET inhibitor, and achieved a partial and durable response. Conclusions: KRAS^WT PDAC is molecularly distinct from KRAS^MUT and enriched with potentially actionable genetic variants. In our study, transcriptomic profiling revealed that the KRAS signaling cascade may play a key role in KRAS^WT PDAC. Our report of a KRAS^WT PDAC patient with TFG-MET rearrangement who responded to a cMET inhibitor further supports the pursuit of precision oncology in this sub-population. Identification of targetable mutations, perhaps through approaches like RNA-seq, can help enable precision-driven approaches to select optimal treatment based on tumor characteristics. [ABSTRACT FROM AUTHOR]

: Copyright of Cancers is the property of MDPI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

المؤلفون: Ahn, Daniel P.

المصدر: Georgetown Journal of International Affairs, 2019 Oct 01. 20, 126-132.

الوصول الحر: https://www.jstor.org/stable/26794951Test

المؤلفون: Golan, Talia, Raitses‐Gurevich, Maria, Kelley, Robin K, Bocobo, Andrea G, Borgida, Ayelet, Shroff, Rachna T, Holter, Spring, Gallinger, Steven, Ahn, Daniel H, Aderka, Dan, Apurva, Jain, Bekaii‐Saab, Tanois, Friedman, Eitan, Javle, Milind

المصدر: The Oncologist. 22(7)

مصطلحات موضوعية: Biomedical and Clinical Sciences, Clinical Sciences, Oncology and Carcinogenesis, Prevention, Digestive Diseases, Clinical Research, Cancer, Genetic Testing, Rare Diseases, Genetics, Breast Cancer, Adult, Aged, BRCA1 Protein, BRCA2 Protein, Bile Duct Neoplasms, Cholangiocarcinoma, Female, Heterozygote, Humans, Male, Middle Aged, Mutation, Retrospective Studies, Survival Rate, BRCA-associated, Germline, somatic, PARPi, Oncology & Carcinogenesis, Oncology and carcinogenesis

الوصف: BackgroundBiliary tract malignancies, in particular cholangiocarcinomas (CCA), are rare tumors that carry a poor prognosis. BRCA2 mutation carriers have an increased risk of developing CCA with a reported relative risk of ∼5 according to the Breast Cancer Linkage Consortium. In addition to this risk, there are potential therapeutic implications in those harboring somatic and/or germline (GL) BRCA mutations. Therefore, it is important to define the clinical characteristics of GL/somatic BRCA1/2 variants in CCA patients.Materials and methodsWe performed a multicenter retrospective analysis of CCA patients diagnosed between January 2000 and December 2013 with GL or somatic variants in BRCA1/2 genes detected by GL mutations testing and/or by tumor next generation sequencing. Cases were identified from clinical databases at participating institutions. Data including demographics, clinical history, surgical procedures, and systemic chemotherapy or radiation were extracted from patients' records.ResultsOverall, 18 cases were identified: 5 carriers of GL BRCA1/2 mutations (4 BRCA2; 1 BRCA1) and 13 harboring somatic variations (7 BRCA1; 6 BRCA2). Mean age at diagnosis was 60, SD ± 10 years (range 36-75 years), with male and female prevalence rates of 61.2% and 38.8%, respectively. Stage at diagnosis was I (n = 4), II (n = 3), III (n = 3), and IV (n = 8). Six patients had extrahepatic CCA and the rest intrahepatic CCA. Thirteen patients received platinum-based therapy and four were treated with poly ADP ribose polymerase inhibitors, of whom one experienced sustained disease response with a progression-free survival of 42.6 months. Median overall survival from diagnosis for patients with stage I/II in this study was 40.3 months (95% confidence interval [CI], 6.73-108.15) and with stages III/IV was 25 months (95% CI, 15.23-40.57).ConclusionBRCA-associated CCA is uncommon. This multicenter retrospective study provides a thorough clinical analysis of a BRCA-associated CCA cohort, which can serve as a benchmark for future development and design of expanded analyses and clinical trials.Implications for practiceBRCA-associated CCA is uncommon but a very important subtype of hepatic malignancies, due to its rising prevalence. Better clinical characterization of this subtype might allow application of targeted therapy for CCA patients with germline or somatic mutations in BRCA1/2 genes, especially due to previously reported success of such therapies in other BRCA-associated malignancies. Thus this study, first of its kind, provides a basis for future multi-centered analyses in larger cohorts, as well as clinical trials. Additionally, this study emphasizes the importance of both germline and somatic genotyping for all CCA patients.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/3g69q1fdTest

المؤلفون: Greschner, Martin, Heitman, Alexander K, Field, Greg D, Li, Peter H, Ahn, Daniel, Sher, Alexander, Litke, Alan M, Chichilnisky, EJ

المصدر: Current Biology. 26(15)

مصطلحات موضوعية: Biological Sciences, Biomedical and Clinical Sciences, Psychology, Eye Disease and Disorders of Vision, Neurosciences, Underpinning research, 1.1 Normal biological development and functioning, Eye, Amacrine Cells, Animals, Electrophysiological Phenomena, Interneurons, Macaca fascicularis, Macaca mulatta, Retina, Visual Pathways, Medical and Health Sciences, Psychology and Cognitive Sciences, Developmental Biology, Biological sciences, Biomedical and clinical sciences

الوصف: Understanding the function of modulatory interneuron networks is a major challenge, because such networks typically operate over long spatial scales and involve many neurons of different types. Here, we use an indirect electrical imaging method to reveal the function of a spatially extended, recurrent retinal circuit composed of two cell types. This recurrent circuit produces peripheral response suppression of early visual signals in the primate magnocellular visual pathway. We identify a type of polyaxonal amacrine cell physiologically via its distinctive electrical signature, revealed by electrical coupling with ON parasol retinal ganglion cells recorded using a large-scale multi-electrode array. Coupling causes the amacrine cells to fire spikes that propagate radially over long distances, producing GABA-ergic inhibition of other ON parasol cells recorded near the amacrine cell axonal projections. We propose and test a model for the function of this amacrine cell type, in which the extra-classical receptive field of ON parasol cells is formed by reciprocal inhibition from other ON parasol cells in the periphery, via the electrically coupled amacrine cell network.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/1gk736s6Test

المؤلفون: Ahn, Daniel H, Barzi, Afsaneh, Ridinger, Maya, Samuëlsz, Errin, Subramanian, Ramanand A, Croucher, Peter J P, Smeal, Tod, Kabbinavar, Fairooz F, Lenz, Heinz-Josef

المصدر: Clin Cancer Res ; ISSN:1557-3265 ; Volume:30 ; Issue:10

الوصف: Onvansertib is a highly specific inhibitor of polo-like kinase 1 (PLK1), with demonstrated safety in solid tumors. We evaluated, preclinically and clinically, the potential of onvansertib in combination with chemotherapy as a therapeutic option for KRAS-mutant colorectal cancer.

العلاقة: https://doi.org/10.1158/1078-0432.CCR-23-3053Test; https://pubmed.ncbi.nlm.nih.gov/38231047Test; https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11094418Test/

الإتاحة: https://doi.org/10.1158/1078-0432.CCR-23-3053Test
https://pubmed.ncbi.nlm.nih.gov/38231047Test
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11094418Test/