tbuckley/cabot-search huggingface dataset:
Abstract 2365: Does a combination of type 2 diabetes mellitus and increased alcohol intake affect prospective total adenoma accumulation
Authors: Martin Tobi, Fadi Antaki, Stephanie Judd, Paula Sochacki, MaryAnn Rambus, Harvinder Talwar, Michael Lawson, Edi Levi, Benita McVicker
Journal: Cancer Research (2020)

Abstract Introduction: Adenoma formation data in diabetics is inconclusive. Alcohol intake (AI), associated with colorectal neoplasia (CRN) has not been systematically studied in diabetes. We investigated effects of diabetes and AI in a prospective patient cohort at increased CRN risk. Methods: Diabetes diagnoses based on patients' problem list, corroborated by HbA1c and glucose levels. Self-reported AI was quantified as more than occasional/social. Cumulative adenoma number were computed using available records. In a subset of patients, CRN-related Paneth cell marker p87 was used to semi-quantify immunohistochemically the colonic regions binding this label. Results: 680 patients (348 diabetics 332 non-diabetic) were ascertained with 12.4-year median follow-up. Diabetics had more adenomas than non-diabetics (2.3±3.54 versus 1.81±2.91, p=0.05) and p87 levels were significantly higher in the descending colon (p&amp;lt;0.03) and rectum (p&amp;lt;0.008). Significant demographic differences of increased black ethnicity, lesser survival, increased BMI and increased smoking were appreciated in diabetics. In non-drinking patients, adenomas were also similarly increased in diabetics and demographics and p87 levels were as reported above without significant smoking differences. Comparing diabetics who drank actively with non-diabetics who did not, the diabetics had increased polyp accumulation (2.90±4.29 versus 1.62±2.45 p&amp;lt;0.012), increased proportion of black ethnicity, increased BMI and were younger. Rectal p87 was significantly increased (p&amp;lt;0.04) without smoking effects on polyp number. Conclusion: Diabetics accumulate more adenomas than controls which is reflected in the increase of left-sided p87 expression. A combination of increased AI and diabetes particularly increases adenoma formation seemingly independent of factors such as age and smoking. Citation Format: Martin Tobi, Fadi Antaki, Stephanie Judd, Paula Sochacki, MaryAnn Rambus, Harvinder Talwar, Michael Lawson, Edi Levi, Benita McVicker. Does a combination of type 2 diabetes mellitus and increased alcohol intake affect prospective total adenoma accumulation [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2365.
Abstract 5367: Identification and clinical value of the circulating tumor cells (CTCs) in the colorectal cancer
Authors: Faysal-Bin Hamid, Farhad Islam, Cu-Tai Lu, Marco Matos, Tracie Cheng, Vinod Gopalan, Alfred King-yin Lam
Journal: Cancer Research (2020)

Abstract The number of circulating tumor cells (CTCs) hase been found as a promising predictive and diagnostic biomarker of colorectal cancer (CRC). The purpose of the study was to enumerate and characterize CTCs from the CRC patients and evaluate the correlation with the clinical stages.Peripheral blood from 57 CRC patients and 6 healthy donors were subjected to isolate CTC by a negative selection (EasySepTM) method. The CTCs were detected by the immunofluorescence staining with the tumor cell markers such as epithelial cell adhesion molecule (EPCAM) and cytokeratin (CK) antibodies and counted them. The extent of positive expressions of EPCAM and cytokeratin (CK) proteins were used to characterize the CTCs and the subpopulations were correlated with the tumor stages of the CRC patients. P&amp;lt;0.05 was considered as statistically significant.CTCs were detected in 72% (41/57) of the CRC patients. Comparing to the healthy donors (HD), the CTC count was higher (p=0.0062) in the CRC patients. In addition, CTC clusters were found in 32% (18/57) of patients with CRC while total CTCs were significantly higher than the cluster count (p=0.001). Among the CRC patients, CTCs were more abundant in the advanced stages compared to the early stages (p=0.0019). Moreover, we found the length of the individual CTCs were significantly larger than the CTCs in the cluster (p&amp;lt;0.0001) and significantly correlated (p=0.036) with the tumor stages. However, we identified the EPCAMPosCkPos subclones in 38 (93%) out of 41 CTC positive cases and a median of 8.0 (range: 0-60) CTCs were counted. In contrast, EPCAMPosCkNeg subpopulations were detected in 27 (66%) patients and the median CTC count was 2.0 (range: 0-18). Interestingly, EPCAMPosCkPos CTC subclones were significantly higher (p=0.011) than EPCAMPosCkNeg subclones, and the number of EPCAMPosCkPos CTCs was merely associated (p=0.0068) with the tumor stages. We conclude that the morphological and phenotypic features of the CTCs are closely relevant to the clinical stages, which could provide vital information to improve the patient stratification and treatment selection. Citation Format: Faysal-Bin Hamid, Farhad Islam, Cu-Tai Lu, Marco Matos, Tracie Cheng, Vinod Gopalan, Alfred King-yin Lam. Identification and clinical value of the circulating tumor cells (CTCs) in the colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5367.
Abstract 2835: Effector T-cell shape is a potential digital biomarker for assessing CD8 lymphocyte activation in colorectal cancer (CRC) tumors
Authors: Natalie Zwing, Xiao Li, Derrek Hibar, Henrik Failmezger, Yao Nie, Fabien Gaire, Konstanty Korski
Journal: Cancer Research (2020)

Abstract With the recent advances in cancer immunotherapy it is critical to identify innovative biomarkers, reflecting the interaction between the tumor and its immune microenvironment. As a model system, CRC tumors are considered as non-immunogenic cancers with minor exception of microsatellite instable (MSI) cases that, in contrast to microsatellite stable (MSS) tumors, are characterized by a high tumor mutational burden (TMB) due to defects in mismatch repair (MMR) genes. These characteristics make MSI tumors more visible for the immune system, causing higher lymphocytic influx. When analyzing T cell kinetics, live cell imaging studies shown that T cells elongate while trafficking and are rounded while interacting or resting in the tissue. Based on these initial observations, we hypothesized that by assessing the density, distribution and shape of CD8 cytotoxic T cells in tumor areas, we could find a surrogate combined digital image-derived biomarker reflecting tumor immune microenvironment dynamics. To visualize this fundamental correlation, multiplexed immunohistochemistry was performed on 74 selected cases of primary CRC from our tissue bank collection with subsequent whole slide image analysis trained by machine learning. The CD8 T cell shape was assessed by nuclear eccentricity, along with PD1 and Ki67 activation status of the detected cell. Spatial plots revealed a haphazard T cell distribution in the overall tumor area, locating round and elongated CD8 T cells in both, tumor epithelium and tumor stroma compartments. Further discrimination of CD8 T cells according to PD1 and Ki67 positivity, showed higher activation / exhaustion in the round shaped T lymphocytes. In addition, we correlated the T cell shape with the MMR status and TMB assigned to the patient. Finally, integration of differential gene expression analysis provided insights into the role of the T cell shape in distinct tumor immune microenvironment conditions. With this novel approach, we discovered a new potential digital biomarker associated with the T effector cell function. Our results warrant further validation on bigger CRC patient cohorts, other tumor indications and through expanding the image analysis scope. Citation Format: Natalie Zwing, Xiao Li, Derrek Hibar, Henrik Failmezger, Yao Nie, Fabien Gaire, Konstanty Korski. Effector T-cell shape is a potential digital biomarker for assessing CD8 lymphocyte activation in colorectal cancer (CRC) tumors [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2835.
The Russian vaccine for COVID-19
Authors: Talha Khan Burki
Journal: The Lancet Respiratory Medicine (2020)

On Aug 11, 2020, Russia became the first country in the world to approve a vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The vaccine, which is based on two adenovirus vectors, was developed by the Gamaleya National Center of Epidemiology and Microbiology (Moscow, Russia). Its approval was announced by President Vladimir Putin. "I know [the vaccine] works quite effectively, helps to develop strong immunity, and has gone through all the necessary tests", declared Putin at a cabinet meeting.
Abstract 2168: A growth rate corrected metric for cytotoxic co-culture systems
Authors: Johannes Christian Melms, Clarence Yapp, Caitlin Elizabeth Mills, Peter Sorger, Benjamin Izar
Journal: Cancer Research (2020)

Abstract Tumor/T-cell co-cultures in combination with large-scale genome-editing tools emerged as powerful tools for discovery of drivers of resistance to immunotherapies. Traditionally, chromium or lactate-dehydrogenase release and/or target cell viability counts before and after co-culture treatment are used as surrogate endpoint assays to estimate the selection pressure applied. These assays cannot dissect growth arrest, cell death, cell viability and target cell outgrowth, all of which occur as a consequence of released cytokines and direct tumor/T-cell interactions, hence, significantly impact the interpretation of small- and large-scale screens in co-culture models. These biases are particularly relevant when comparing cell lines or genotypes with different growth kinetics. Here, we use a dual reporter system and adopt pharmaco-mathematical principles to dissect these biases to create a growth-rate corrected co-culture metric (GRC), which normalizes T-cell mediated antiproliferative and cytotoxic effects in tumor target cells. We illustrate the value of this metric by comparing fast and slow-growing tumor cells in autologous patient-derived melanoma/T-cell co-culture pairs. At tumor-T-cell ratios resulting in a half maximal relative reduction of target cell counts compared to controls, the fast-proliferating cell line had not changed in absolute cell counts since baseline while the slow-growing cell line showed a 50% reduction. This indicates that in one instance (fast growing cell line) growth-retardation occurred due to a balance of immune editing and target cell proliferation, while in the other (slow-growing cell line) T-cell mediated killing resulted in net loss of tumor cells. Using GRC, these differences can be readily distinguished, and comparable selection conditions can be selected. This has important implications for large-scale screens with perturbations within cancer cells: drop-outs from a screen in the fast-growing cell line would not only contain perturbations that increase specific sensitivity to T-cell mediated cytotoxicity, but also perturbations causing a general loss in proliferation/survival fitness. In addition, some of the discrepancy in recently published screens may be explained by differences in models with varying proliferation rates and therefore selection conditions. In summary, the GRC metric enhances the interpretation of co-culture experiments and could contribute to improved selection of targets from large-scale screens investigating resistance to T-cell mediated toxicity for drug development. Citation Format: Johannes Christian Melms, Clarence Yapp, Caitlin Elizabeth Mills, Peter Sorger, Benjamin Izar. A growth rate corrected metric for cytotoxic co-culture systems [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2168.
Targeting FcRn for immunomodulation: Benefits, risks, and practical considerations
Authors: Hans-Hartmut Peter, Hans D. Ochs, Charlotte Cunningham-Rundles, Donald C. Vinh, Peter Kiessling, Bernhard Greve, Stephen Jolles
Journal: Journal of Allergy and Clinical Immunology (2020)

The neonatal fragment crystallizable (Fc) receptor (FcRn) functions as a recycling mechanism to prevent degradation and extend the half-life of IgG and albumin in the circulation. Several FcRn inhibitors selectively targeting IgG recycling are now moving rapidly toward clinical practice in neurology and hematology. These molecules accelerate the destruction of IgG, reducing pathogenic IgG and IgG immune complexes, with no anticipated effects on IgA, IgM, IgE, complement, plasma cells, B cells, or other cells of the innate or adaptive immune systems. FcRn inhibitors have potential for future use in a much wider variety of antibody-mediated autoimmune diseases. Given the imminent clinical use, potential for broader utility, and novel mechanism of action of FcRn inhibitors, here we review data from 4 main sources: (a) currently available activity, safety, and mechanism-of-action data from clinical trials of FcRn inhibitors; (b) other procedures and treatments that also remove IgG (plasma donation, plasma exchange, immunoadsorption); (c) diseases resulting in loss of IgG; and (d) primary immunodeficiencies with potential mechanistic similarities to those induced by FcRn inhibitors. These data have been evaluated to provide practical considerations for the assessment, monitoring, and reduction of any potential infection risk associated with FcRn inhibition, in addition to highlighting areas for future research.
Abstract 2332: Correlation of lifestyle factors with epigenetic aging unveiled in the practice of a DNA methylation-based age test
Authors: Wei Guo, Yap Ching Chew, Xiaojing Yang, Michiko Suwoto, Taikun Yamada, Xi Yu Jia
Journal: Cancer Research (2020)

Abstract Background: DNA methylation clocks have been developed recently to estimate epigenetic age which is associated with chronological age in mouse and human. Changes in epigenetic age were reported in patients with health conditions including cancer. Different from genetic variations, epigenetic properties can be modified by environmental factors. Epigenetic age tests using blood samples have been offered directly to customers recently. We sought to analyze relationships between epigenetic aging and lifestyle factors, medication and aging interventions in the hope of assisting healthier living. Methods: Epigenetic age, called DNAge, is estimated using linear regression of DNA methylation levels at 206 loci containing 1344 CpGs and chronological age. Delta age is defined as the difference of epigenetic age minus chronological age. Correlations between lifestyle factors or medication and delta age of hundreds of whole blood samples were evaluated using biweight midcorrelation. Statistical significance is set at 0.05. Results: Our results showed positive correlations between accelerated epigenetic aging and BMI (bicor=0.148, p=0.009, n=311), current smoker (bicor=0.143, p=0.011, n=315), or stress (bicor=0.088, p=0.128, n=302). Factors with positive correlation but not reaching statistical significance included total cholesterol, alcohol consumption and Keto diet. Factors with negative correlation but not statistically significant included exercise, balanced diet, mostly meat, mostly vegetables, and education. Conclusions: The epigenetic age analysis of real customer data confirmed beneficial and adversarial health effects of certain lifestyle factors. The DNAge test offered proves to be useful as a biomarker for biological age and as a practical tool for monitoring and evaluation of health status which may be used in cancer epidemiology study and help cancer prevention. Citation Format: Wei Guo, Yap Ching Chew, Xiaojing Yang, Michiko Suwoto, Taikun Yamada, Xi Yu Jia. Correlation of lifestyle factors with epigenetic aging unveiled in the practice of a DNA methylation-based age test [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2332.
Phase Ib Study of Ribociclib plus Fulvestrant and Ribociclib plus Fulvestrant plus PI3K Inhibitor (Alpelisib or Buparlisib) for HR+ Advanced Breast Cancer
Authors: Sara M. Tolaney, Young-Hyuck Im, Emiliano Calvo, Yen-Shen Lu, Erika Hamilton, Andres Forero-Torres, Thomas Bachelot, Michela Maur, Angelica Fasolo, Ralph Tiedt, Lisa Nardi, Uz Stammberger, Ahmed M. Abdelhady, Shiling Ruan, Soo Chin Lee
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Resistance to treatment with endocrine therapy in patients with HR+, HER2− advanced breast cancer (ABC) is common and dual inhibition of CDK4/6 and PI3K pathways may delay the development of resistance. This phase Ib trial evaluates the safety and tolerability of triple and double regimens containing the CDK4/6 inhibitor ribociclib. Patients and Methods: In this open-label, multicenter, phase Ib study, 70 postmenopausal women with HR+, HER2− ABC were enrolled into one of four treatment combinations: ribociclib (once daily, 3 weeks on, 1 week off) plus fulvestrant; ribociclib (continuous dosing) plus fulvestrant; ribociclib plus alpelisib plus fulvestrant; or ribociclib plus buparlisib plus fulvestrant. Results: The recommended phase II dose (RP2D) of ribociclib was confirmed to be 600 mg (3 weeks on, 1 week off) and 400 mg (continuous dosing) plus fulvestrant 500 mg. For the triple combination with buparlisib, the RP2D was ribociclib 400 mg plus buparlisib 30 mg plus fulvestrant 500 mg. Enrollment for the triple combinations was stopped due to unexpected toxicity. No RP2D was determined for the alpelisib combination. The safety profiles of the ribociclib plus fulvestrant combinations were consistent with those in previous studies. There was no marked difference in ribociclib exposure in the presence of triple-combination partners. The highest overall response rate was seen in the buparlisib triple combination (25.0%; 95% confidence interval, 9.8–46.7). Conclusions: Ribociclib plus fulvestrant demonstrated safety in the treatment of patients with HR+, HER2− ABC. Triple combinations with alpelisib or buparlisib plus fulvestrant are not recommended for phase II investigation. See related commentary by Clark et al., p. 371
Intramural generated Angiotensin 1-7 mediates splanchnic vasodilation via mas-receptor stimulation and thereby vascular dysfunction in cirrhosis
Authors: Sabine Klein, Josephine A Grace, Michaela Granzow, Robert Schierwagen, Chandana B Herath, Louise M Burrell, Peter W Angus, Tilman Sauerbruch, Jonel Trebicka
Journal: Hepatology (2012)
Digital technology, tele-medicine and artificial intelligence in ophthalmology: A global perspective
Authors: Ji-Peng Olivia Li, Hanruo Liu, Darren S.J. Ting, Sohee Jeon, R.V. Paul Chan, Judy E. Kim, Dawn A. Sim, Peter B.M. Thomas, Haotian Lin, Youxin Chen, Taiji Sakomoto, Anat Loewenstein, Dennis S.C. Lam, Louis R. Pasquale, Tien Y. Wong, Linda A. Lam, Daniel S.W. Ting
Journal: Progress in Retinal and Eye Research (2020)
Abstract 6396: Sarcoma treatment using HSP90 inhibitors in combinatorial synergy with doxorubicin
Authors: Matt Kirkham, Sarah Luelling, Kaniz Fatema, Jared Barrott
Journal: Cancer Research (2020)

Abstract Synovial sarcoma, a rare muscle cancer, has few targeted therapies, and is most commonly treated using doxorubicin (DOX). Even as a primary treatment agent, successful treatment and remission rates are low, and the significant cardiotoxicity of DOX limits dosage options. Synovial sarcoma, and other sarcomas, have a high expression of HSP90, a protein that acts as a chaperone molecule to stabilize and help fold other proteins within the cellular matrix. Under high stress situations, HSP90 is upregulated and acts to stabilize other more thermally labile proteins, including many oncogenes. Using FDA approved drug panels, it was determined that HSP90 is a suitable target for treatment. We look to use a novel HSP90 inhibitor (HS10) compound, to target the high expression of HSP90 within synovial sarcoma and osteosarcoma in combination with the chemotherapy standard DOX to determine if a synergistic effect is observed. This synergistic effect would allow for an overall decreased dose to induce effective cancer cell targeting, reducing overall systemic toxicity within patients. Our results indicate such synergism does occur between DOX and HS10, at a dosage of 5-25 nM DOX and 1000 nM HS10, reducing cell survival to 37-68%, dependent on cell line. DOX dosage alone reduced cell survival to 74% in the most effective case, with no reduction in the least effective case, at a dose of 100 nM. This dose is four times stronger than the highest DOX synergistic dose. It can be concluded, then, that synergistic combination does exist between DOX and HS10, and dosage of DOX can be reduced with more effective targeting for synovial and osteosarcoma cell lines. Protein expression was evaluated using immunoblotting to isolate protein fractions within the cytoplasm and cell membrane, showing high expression within the cytoplasm. Isolated blood plasma from mice with and without tumors was analyzed through ELISA, showing elevated HSP90 presence in mice with tumors (236.4±190pg) vs mice without tumors (6.5±3.5pg). This confirmation of elevated HSP90 expression within sarcoma patients suggests targeting using HS10 to induce synergy to be a viable approach for advanced sarcoma treatment. Citation Format: Matt Kirkham, Sarah Luelling, Kaniz Fatema, Jared Barrott. Sarcoma treatment using HSP90 inhibitors in combinatorial synergy with doxorubicin [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 6396.