tbuckley/cabot-search huggingface dataset:
Abstract 3: Deep learning-based integration of esophageal cancer morphology with genomics
Authors: Ruchika Verma, Wei Wu, Neeraj Kumar, Elizabeth Yu, Won-Tak Choi, Sarah Umetsu, Trever Bivona
Journal: Cancer Research (2021)

Abstract Esophageal cancer is a major cause of cancer mortality world-wide. Even with advanced treatment options available, patients with esophageal cancer have a poor 5-year survival rate of 16%. Genomic studies of esophageal cancer have revealed frequently mutated genes involved in different oncogenic pathways. In this study, we attempted to predict genomic alterations, pathological and clinical features directly from H&amp;E-stained whole slide images (WSIs) of individual esophageal cancer cases by utilizing modern deep learning methods. We used WSIs with esophageal cancer obtained from TCGA and annotated cancerous epithelial and stromal components separately for esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC) (n= 25 cases for each) to create a training set. Subsequently, patches of size 256×256 pixels were extracted, and a U-Net convolutional neural network (CNN) was trained for semantic segmentation of tumor epithelium and stromal pixels. Tumor epithelium regions identified by the first U-Net CNN were fed into a Squeezenet model to learn to distinguish between EAC and ESCC in the training phase. Finally, for each subtype (EAC and ESCC), separate Densenet models were trained to predict gene mutation status. We also trained independent Densenet models to predict tumor stage, grade, and survival outcome from the tumor epithelial patches. After training, we tested these models on an independent validation set obtained from TCGA (n = 99) and UCSF (n = 25) patients, ensuring patient level separation between the training and the validation sets. We obtained an average AUC of 0.90 and 0.87 for epithelium vs. stromal and EAC vs. ESCC classification, respectively, on the validation datasets. These models enabled us to predict tumor stage, grade, and survival outcome with an accuracy of &amp;gt; 0.9. TP53 gene alterations were detected in over 50% of esophageal cancer cases, and our model was able to predict TP53 gene mutation status on WSIs with an AUC of 0.91. Overall, this study demonstrates how deep learning algorithms can aid in better understanding and predicting key biological and clinical features of aggressive malignancies at both population and individual patient level. This integration of artificial intelligence with molecular and histopathologic features could also help to accelerate precision cancer diagnosis and treatment in the clinical setting. Citation Format: Ruchika Verma, Wei Wu, Neeraj Kumar, Elizabeth Yu, Won-Tak Choi, Sarah Umetsu, Trever Bivona. Deep learning-based integration of esophageal cancer morphology with genomics [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 3.
Survival among patients with relapsed/refractory diffuse large B cell lymphoma treated with single-agent selinexor in the SADAL study
Authors: Marie Maerevoet, Josee M. Zijlstra, George Follows, Rene-Olivier Casasnovas, J. S. P. Vermaat, Nagesh Kalakonda, Andre Goy, Sylvain Choquet, Eric Van Den Neste, Brian Hill, Catherine Thieblemont, Federica Cavallo, Fatima De la Cruz, John Kuruvilla, Nada Hamad, Ulrich Jaeger, Paolo Caimi, Ronit Gurion, Krzysztof Warzocha, Sameer Bakhshi, Juan-Manuel Sancho, Michael Schuster, Miklos Egyed, Fritz Offner, Theodoros P. Vassilakopoulos, Priyanka Samal, Matthew Ku, Xiwen Ma, Kelly Corona, Kamal Chamoun, Jatin Shah, Sharon Shacham, Michael G. Kauffman, Miguel Canales
Journal: Journal of Hematology & Oncology (2021)

Abstract Patients with RR DLBCL who have received ≥ 2 lines of therapy have limited treatment options and an expected overall survival (OS) of &lt; 6 months. The SADAL study evaluated single-agent oral selinexor in patients with RR DLBCL and demonstrated an overall response rate (ORR) of 29.1% with median duration of response (DOR) of 9.3 months. The analyses described here evaluated a number of subpopulations in order to understand how response correlates with survival outcomes in order to identify patients who could most optimally benefit from selinexor treatment. Median age was 67 years; 44.8% of patients were ≥ 70 years of age. The median OS was 9.0 months (95% CI 6.2, 13.7) at a median follow-up of 14.8 months. The median OS was not reached in patients with a CR or PR, while patients who did not respond have a median OS of 4.9 months ( p &lt; 0.0001). Patients &lt; 70 years had an OS of 11.1 months compared with 7.8 months in patients ≥ 70 years. Among patients with or without prior ASCT, the median OS was 10.9 and 7.8 months, respectively. Among patients with disease refractory to the most recent DLBCL treatment regimen, the median OS was 7.0 months compared with 11.1 months for disease not refractory to the most recent treatment. In a patient population in which survival is expected to be &lt; 6 months, treatment with single-agent oral selinexor was associated with a median survival of 9 months. Increased median OS observed in patients responding to selinexor was consistent across subgroups regardless of age, prior ASCT therapy, or refractory status. Randomized studies of selinexor in combination with a variety of other anti-DLBCL agents are planned. This trial was registered at ClinicalTrials.gov (NCT02227251) on August 28, 2014. https://clinicaltrials.gov/ct2/show/NCT02227251 .
Assessment of Screening Mammography Recommendations
Authors: Paul L. Baron, Julie A. Margenthaler, Jill R. Dietz
Journal: JAMA Internal Medicine (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Abstract 570: Detecting cancer using genome-wide cfDNA nucleosomal fragmentation in a prospective multi cancer cohort
Authors: Jacob Carey, Alessandro Leal, Bryan Chesnick, Denise Butler, Michael Rongione, Sian Jones, Rob Scharpf, Mette Villadsen, Stig E. Bojesen, Julia S. Johansen, Claus L. Feltoft, Victor E. Velculescu, Nicholas C. Dracopoli
Journal: Cancer Research (2021)

Abstract Genome-wide cfDNA fragmentation patterns have previously been demonstrated to distinguish with high sensitivity and specificity between plasma samples from individuals with and without cancer. To further evaluate cfDNA fragmentation as a blood-based screening test for cancer, we have used low coverage whole genome sequencing to analyze plasma samples from 280 patients referred to an advanced diagnostic center due to non-organ specific signs and symptoms of cancer. Within three months of inclusion, 74 of these patients were diagnosed with one of 16 different solid cancers while 206 patients did not have cancer. Using an improved version of our genome-wide cfDNA fragmentation analyses, we observed high performance in distinguishing cancer and non-cancer samples (AUC=0.92, 95% CI 0.88-0.96), including lung cancer (n=12, AUC=0.91, 95% CI 0.80-1.00) and colorectal cancer (n=12, AUC=0.94, 95% CI 0.89-0.99). Although many of the patients in this cohort had other common illnesses including cardiovascular, autoimmune, and inflammatory diseases, the machine learning models of cfDNA fragmentation were able to detect cancer with high sensitivity and specificity. These data support the development of genome-wide cfDNA fragmentation analyses as a non-invasive detection screening approach for both single and multiple cancers. Citation Format: Jacob Carey, Alessandro Leal, Bryan Chesnick, Denise Butler, Michael Rongione, Sian Jones, Rob Scharpf, Mette Villadsen, Stig E. Bojesen, Julia S. Johansen, Claus L. Feltoft, Victor E. Velculescu, Nicholas C. Dracopoli. Detecting cancer using genome-wide cfDNA nucleosomal fragmentation in a prospective multi cancer cohort [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 570.
Complications, revision and perceived health after surgery for stress urinary incontinence by mid urethra sling inthe VIGI-MESH register: Description and medium-term incidence for 1814 women
Authors: T. Charles, L. Wagner, S. Campagne-Loiseau, P. Ferry, C. Saussine, M. Cosson, X. Deffieux, M. Hummel, L. Panel, J.-P. Lucot, P. Debodinance, C. Carlier-Guérin, A.-C. Pizzoferrato, A. Vidart, T. Thubert, R. Ramanah, E. Nkounkou, A. Fauconnier, X. Fritel
Journal: European Urology (2021)
Urologists, sex and pandemic. How did we do?
Authors: M. Capdevila Gonzalo, F. Agreda Castañeda, A. Vicens Morton, J. Torremade Barrena, P. Luque Galvez, R. Cocera Rodriguez, V. Parejo Cortes, J.M. Corral Molina
Journal: European Urology (2021)
Abstract 610: Paired alterations of 35-gene expressing profiles before and after neoadjuvant chemoradiation in esophageal squamous cell carcinoma patients impact clinical prognosis
Authors: Yu-Jen Chen, Prerana Bhan, Terry Wu, Hang Chang, Chi-Jung Lee
Journal: Cancer Research (2021)

Abstract Purpose: Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is widely used for treating locally advanced esophageal cancer in the thorax. The aim of this study was to evaluate alterations of the 35-gene expression profiles in irradiated esophageal tissues before and after chemoradiation. Materials and Methods: A total number of 50 patients with Esophageal squamous cell carcinoma (ESCC) received neoadjuvant CCRT were retrospectively reviewed. The prescribed radiation dose for gross tumor and metastatic lymph nodes or subclinical mucosal/submucosal disease and regional lymphatic basin were 48 Gy and 43.2 Gy, respectively. All patients underwent CCRT using the intensity-modulated radiation therapy in 24 fractions and received concurrent chemotherapy with cisplatin. A 35-gene expression profile derived from reported ESCC-specific next-generation sequencing was performed. Paired 35-gene expression profiles were analyzed using pre-CCRT biopsy and post-CCRT esophagectomy specimens. In vitro validation of differential expression genes by using human ESCC cell lines 81T and TE2 was performed using the same 35-gene panel. Results: The alterations in mutation of genes between pre-CCRT biopsy and post-CCRT surgical specimens (delta expression profiles) correlated with pathological complete remission, overall survival and progression free survival. Among the delta expression profiles, the most significant alterations with prognostic impact were noted in MYH4 (p.Gln1210fs) and TTN (p.Asp7145His). Mutation of MYH4 (p.Gln1210fs) and TTN (p.Asp7145His) were demonstrated with favorable and unfavorable impact on rate of pathological complete remission, respectively. The mutation of MYH4 was also noted in human ESCC cell lines 81T and TE2 cells. Conclusion: By using the 35-gene expression profiles, specific mutations correlated to prognosis in esophageal squamous cell carcinoma patients receiving neoadjuvant chemoradiation and esophagectomy were found. The role of MYH4 mutation in treatment outcome and development as therapeutic target of esophageal squamous cell carcinoma remains to be clarified. Citation Format: Yu-Jen Chen, Prerana Bhan, Terry Wu, Hang Chang, Chi-Jung Lee. Paired alterations of 35-gene expressing profiles before and after neoadjuvant chemoradiation in esophageal squamous cell carcinoma patients impact clinical prognosis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 610.
Assessment of Screening Mammography Recommendations—Reply
Authors: Jennifer L. Marti
Journal: JAMA Internal Medicine (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
CXCR4 Expression Demonstrated by 68Ga-Pentixafor PET/CT Imaging in a Case of Systemic Mastocytosis Mimicking Lymphoma
Authors: Murat Yilmaz Kiran, Evsen Apaydin Arikan, Yasemin Sanli, Gulcin Yegen, Serkan Kuyumcu
Journal: Clinical Nuclear Medicine (2021)

Abstract 68 Ga-Pentixafor is a novel radiotracer for imaging chemokine receptor subtype 4 (CXCR4) receptors, which are expressed exceptionally high in several hematologic malignancies, including various types of lymphoma. Herein we report a case of a 64-year-old man patient with suspected hematologic malignancy who underwent 18 F-FDG and 68 Ga-pentixafor PET/CT. Both scans demonstrated diffusely increased activity related to bone marrow involvement. 68 Ga-Pentixafor PET/CT demonstrated CXCR4-expressing intra-abdominal lymph nodes that were not detected by 18 F-FDG PET/CT. The patient was highly suspicious of lymphoma; however, histopathological examination of the bone marrow revealed systemic mastocytosis with associated myelofibrosis.
Abstract 462: The development of a highly efficient diagnostic marker combined with PSA of prostate cancer (PCa)
Authors: SeungBaek Lee, JungJin Kim
Journal: Cancer Research (2021)

Abstract Prostate-Specific Antigen (PSA) is a well-known diagnosis maker for detecting prostate cancer (PCa) using a serum test. However, PSA testing remains controversial because it shows a high false-positive rate and lacks the sensitivity of PCa patients with low PSA levels, although patients have metastasis. Recently, we found an E3 ubiquitin ligase, WSB1, highly expressed in PCa patients with low PSA levels. Overexpressed WSB1 is found in various human cancers, such as pancreatic cancer, lung cancer, breast cancer, and PCa. Especially with PCa, WSB1 is highly expressed in metastatic PCa. Using RNA seq. database from PCa patients (65 primaries and 25 metastasis), we found that WSB1 is highly expressed in 90% (9/10) of patients among ten primary patients with normal PSA levels and 100% (6/6) of patients among six metastasis patients with normal PSA levels. WSB1 expression shows a significant correlation with aggressive PCa progression. Furthermore, WSB1 can secrete into cell culture media like PSA. Therefore, we suggest that WSB1 could be a highly efficient marker combined with PSA for PCa diagnosis as well as being developed as a screening test for the early detection of PCa in the high-risk group. Citation Format: SeungBaek Lee, JungJin Kim. The development of a highly efficient diagnostic marker combined with PSA of prostate cancer (PCa) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 462.
Abstract 1722: Enhancement of anti-tumor T-cell immunity by means of an oral small molecule targeting the intracellular immune checkpoint MAP4K1
Authors: Gabriele Leder, Rafael Carretero, Jeffrey Mowat, Sandra Berndt, Roland Neuhaus, Nuria Aiguabella Font, Ulf Boemer, Oliver von Ahsen, Uwe Eberspaecher, Judith Guenther, Mareike Grees, Corinna Link, Barbara Nicke, Daniel Baumann, Martina Schaefer, Mine Oezcan-Wahlbrink, Nicolas D. Werbeck, Ingo Hartung, Bertolt Kreft, Rienk Offringa
Journal: Cancer Research (2021)

Abstract Immune checkpoint blockade using antibodies targeting the cell surface expressed proteins CTLA-4, PD-1 and PD-L1 has revolutionized cancer care and its clinical impact in several indications has prompted a search for complementary immunostimulatory approaches that can further increase the efficacy of these drugs. Mitogen-activated protein kinase kinase kinase kinase 1 (MAP4K1; HPK1), a serine/threonine kinase expressed exclusively in hematopoietic cell lineages, mediates a negative feedback signal downstream of T-cell receptor stimulation. Its activity is enhanced by PGE2 and TGFβ, factors commonly present in the tumor microenvironment. Mice deficient for MAP4K1 or expressing a kinase-dead variant of MAP4K1 exhibit enhanced T-cell function, including increased anti-tumor immunity. We developed the small molecule inhibitor BAY-405 that displays potent nanomolar MAP4K1 inhibition in biochemical and cellular assays, good kinase selectivity, and in vivo exposure after oral dosing. Pharmacological inhibition of MAP4K1 enhances T-cell immunity and overcomes the suppressive impact of PGE2, TGFβ and CD4+ T-regulatory cells. Single agent treatment of tumor-bearing mice results in suppression of tumor outgrowth in several syngeneic models. This is accompanied by an increase in the anti-tumor T-cell response, dependent on an intact T-cell compartment, while not involving direct anti-tumor cytotoxicity. Inhibition of MAP4K1 in conjunction with PD-L1 blockade results in further suppression of tumor outgrowth. Moreover, we found that MAP4K1 is expressed in both PD-L1-high and PD-L1-low human cancers. In summary, our data show that selective inhibition of MAP4K1 by means of small molecule drugs may be used to expand the patient population responding to immune checkpoint inhibition. Citation Format: Gabriele Leder, Rafael Carretero, Jeffrey Mowat, Sandra Berndt, Roland Neuhaus, Nuria Aiguabella Font, Ulf Boemer, Oliver von Ahsen, Uwe Eberspaecher, Judith Guenther, Mareike Grees, Corinna Link, Barbara Nicke, Daniel Baumann, Martina Schaefer, Mine Oezcan-Wahlbrink, Nicolas D. Werbeck, Ingo Hartung, Bertolt Kreft, Rienk Offringa. Enhancement of anti-tumor T-cell immunity by means of an oral small molecule targeting the intracellular immune checkpoint MAP4K1 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1722.
Abstract 1970: Preclinical candidate TQB3824, a small molecule inhibitor of CDC7, shows strong antitumor efficacy in colorectal and pancreatic tumor models
Authors: Gang Li, Xiquan Zhang, Ling Yang, Xin Tian, Zhong xiong, Lihong Hu, Yuanfeng xia, Chi-chung chan, Charles Z. Ding, Shuhui Chen
Journal: Cancer Research (2021)

Abstract Objective: Cell division cycle 7 (CDC7), a receptor serine/threonine kinase which features high-affinity with protein DBF4, plays an important role in DNA replication and DNA damage response via MCM2 phosphorylation. CDC7 has been reported to be up-regulated by about 50% in various human cancers and is being investigated as a therapeutic target in clinical trials. The purpose of this study is to investigate the in-vitro and in-vivo antitumor activities of TQB3824, a small molecule of CDC7 kinase inhibitor, in preclinical models with CDC7 overexpression. Method: Kinase inhibition activities of TQB3824 were determined with CDC7/DBF4 kinase assays. Cellular anti-proliferative activities were evaluated in COLO205 cell line and NCI-H226 cell line, which features CDC7 overexpression and no CDC7 expression, respectively. Three CDX models, colorectal cancer COLO205/SW620 and pancreatic cancer CAPAN-1 with KRAS mutation, were used to test the efficacy of TQB-3824 in vivo. Result: TQB3824 showed potent activities in both kinase inhibition and COLO205 cell anti-proliferation, with IC50 of 2.9 nM and 14.5 nM, separately. In contrast, TQB3824 showed much weaker anti-proliferative activity in NCI H226 cells with IC50 of 8154 nM. TQB3824 displayed strong antitumor efficacy in CDC7 highly expressed colorectal cancer CDX model COLO205 (TGI = 77% @5 mpk, BID), SW620 CDX model (TGI = 100% @5 mpk, BID), and pancreatic cancer CAPAN-1 CDX model (TGI = 115% @6 mpk, BID). Conclusion: We have identified a novel potent CDC7 inhibitor TQB3824, which shows high antitumor efficacy in CDC7 overexpressed solid tumor models. TQB3824 represents a promising clinical candidate for treating solid tumors with high CDC7 expression. Citation Format: Gang Li, Xiquan Zhang, Ling Yang, Xin Tian, Zhong xiong, Lihong Hu, Yuanfeng xia, Chi-chung chan, Charles Z. Ding, Shuhui Chen. Preclinical candidate TQB3824, a small molecule inhibitor of CDC7, shows strong antitumor efficacy in colorectal and pancreatic tumor models [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1970.