tbuckley/cabot-search huggingface dataset:
Abstract 1579: Oncolytic adenovirus Delta-24-RGDOX collaborates with adoptive cell therapy to sustain anti-tumor immunity
Authors: Hong Jiang, Teresa T. Nguyen, Dong Ho Shin, Sagar S. Sohoni, Sumit Gupta, Yanhua Yi, Xuejun Fan, Candelaria Gomez-Manzano, Juan Fueyo
Journal: Cancer Research (2021)

Abstract Oncolytic virotherapy and adoptive T cell therapy (ACT) are promising strategies for cancer treatment, but both are underdeveloped into routine clinical interventions for solid tumors. We reported previously that localized treatment with oncolytic adenovirus Delta-24-RGDOX (DNX-2440), which expresses immune co-stimulator OX40 ligand, stimulated tumor-specific T cells proliferation and migration to untreated disseminated tumors. We hypothesize that intratumorally injected Delta-24-RGDOX complements with ACT to overcome antigen escape, leading to more sustainable anti-cancer effect. To test the hypothesis, we used B16-OVA-C57BL/6 subcutaneous (s.c.)/s.c. melanoma model to assess the effect of the combination therapy. Briefly, 10 days after the first tumor implantation, we injected OVA-specific CD8+ T cells from OT-I mice into the first tumor, followed by three injections of Delta-24-RGDOX into the same tumor. We found the combination was more potent to inhibit the injected 1st tumor and untreated disseminated 2nd tumor growth and resulted in improved survival rate than either of the agent alone (p less than 0.05). Interestingly, we observed relapse of the regressed tumors in the group treated by T cells alone, which recapitulated the effect of CAR T therapy in cancer patients. But the relapse was not observed in most of the mice from the combination group, indicating the combination induces more sustainable tumor regression than T cells alone. The survivors from the combination therapy were protected from rechallenging with B16-OVA cells but not lung carcinoma cells, suggesting the development of immune memory against the same tumor cells. Furthermore, profiling the tumor-infiltrating lymphocytes with flow cytometry revealed that the combination promotes the T cell presence within the tumor and increase the population of the T cells targeting other antigens in addition to the original ACT targeted antigen. Collectively, the results demonstrate that Delta-24-RGDOX collaborates with ACT to induce more potent systemic immunity against the tumors, leading to more sustainable tumor regression and improved survival rate. Our study suggests the virus induces antigen spread, resulting in T cell repertoire to target more tumor-associated antigens to overcome cancer relapse due to cancer heterogeneity and limited targets in ACT and CAR T therapy. Citation Format: Hong Jiang, Teresa T. Nguyen, Dong Ho Shin, Sagar S. Sohoni, Sumit Gupta, Yanhua Yi, Xuejun Fan, Candelaria Gomez-Manzano, Juan Fueyo. Oncolytic adenovirus Delta-24-RGDOX collaborates with adoptive cell therapy to sustain anti-tumor immunity [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 1579.
Should Patients with High-risk Localised or Locally Advanced Prostate Cancer Receive Abiraterone Acetate in Addition to Androgen Deprivation Therapy? Update on a Planned Analysis of the STAMPEDE Trial
Authors: Gerhardt Attard, Louise C. Brown, Noel W. Clarke, Mahesh K.B. Parmar, Nicholas D. James
Journal: European Urology (2021)
Abstract 3023: B7 H3 and autophagy in medulloblastoma
Authors: Ayse E. Kesaf, Katherine Shishido, Kiran K. Velpula, Swapna Asuthkar
Journal: Cancer Research (2021)

Abstract B7-H3 and Autophagy in Medulloblastoma (MB) is the most common malignant pediatric brain tumor and we reported high expression of the immune checkpoint protein, B7-H3. We also showed that B7-H3 promotes exosome secretion, with a plausible cross-talk between exosomes and autophagy in tumor development. Autophagy promotes or suppresses tumorigenesis but its role in pediatric brain tumors has not be elucidated. As our recent research has shown, the elevated levels of B7-H3 in MB enhances exosome secretion that may regulate autophagy processes favoring tumorigenesis over tumor suppression. Therefore, the goal of this study is to investigate the relationship between B7-H3 and autophagy pathways in MB in efforts to improve treatment options and patient survival. Datamining studies conducted using MB patient datasets showed a negative correlation between B7-H3 and autophagy markers; Beclin1, LC3, and ATGs. Kaplan-Meier analysis further demonstrated an inverse relationship between autophagy markers and B7-H3 in the survival curves. Next, using human autophagy array, we observed significant reduction in the expression of Beclin1, LC3, and ATGs upon B7-H3 overexpression in D425 cells. In a separate experiment, we show that silencing B7-H3 using specific shRNA resulted in increased levels of LC3-II. Functional studies performed using FACs analyses and clonogenic assay on shB7-H3 treated- D425, UW228 cells revealed that inhibition of B7-H3 was associated with augmented apoptosis and reduction in colony formation, respectively. These results demonstrate the negative role of B7-H3 in MB autophagy regulation. Therefore, inhibition of B7-H3 may prove effective at promoting autophagy-mediated cell death in MB cells. Citation Format: Ayse E. Kesaf, Katherine Shishido, Kiran K. Velpula, Swapna Asuthkar. B7 H3 and autophagy in medulloblastoma [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 3023.
Comparison of Spending on Common Generic Drugs by Medicare vs Costco Members
Authors: Erin Trish, Laura Gascue, Rocio Ribero, Karen Van Nuys, Geoffrey Joyce
Journal: JAMA Internal Medicine (2021)

This cross-sectional study uses 2017 and 2018 Medicare Part D clams to compare the amount Medicare pays for common generic prescriptions in Part D with prices available to patients without insurance at Costco.
Abstract 1956: Lycorine promotes cell senescence of hepatocellular carcinoma by regulating CDK1
Authors: Haiyang Yu, Shuangshuang Yin, Yuling Qiu, Yanming Luo, Gaoyong Hu, Jia Lu, Shiyue Zhou, Tao Wang
Journal: Cancer Research (2021)

Abstract Hepatocellular carcinoma (HCC) is a serious threat to human health because of its high malignancy and low survival rate. The abnormal expression of genes along with the development of HCC, especially the genes related to the cell cycle. The abnormal expression of these genes in the growth of tumor cells makes them out of the original orbit and out of control. CDKs play critical part in cell cycle control, transcription, and development. Lycorine, a natural products, extract from lycoris radiate, possess biological activities. In this study, we found that Lycorine could up regulated the senescence related protein expression such as p16,p27,p21, however, CDK1 knockout also promote the occurrence of senescence. Unexpectedly, we found that lycorine inhibited CDK1 expression and promoted senescence with a dose-dependent manner in HCC cells, the results of CETSA and DARTS assay also showed that Lycorine could slow down the degradation rate of CDK1 protein; all findings indicated that lycorine might directly inhibit the expression of CDK1 to restrain the occurrence and development of HCC. These findings may provide a new perspective for the treatment of HCC. Citation Format: Haiyang Yu, Shuangshuang Yin, Yuling Qiu, Yanming Luo, Gaoyong Hu, Jia Lu, Shiyue Zhou, Tao Wang. Lycorine promotes cell senescence of hepatocellular carcinoma by regulating CDK1 [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 1956.
Abstract 772: A novel recurrence-associated metabolic prognostic model for risk stratification and therapeutic responses prediction in patients with stage I lung adenocarcinoma
Authors: Chengming Liu, Nan Sun, Jie He
Journal: Cancer Research (2021)

Abstract Background: The proportion of patients with stage I lung adenocarcinoma (LUAD) has dramatically increased with the prevalence of low-dose computed tomography use for screening. Up to 30% of patients with stage I LUAD experience recurrence within 5 years after curative surgery. A robust risk stratification tool is urgently needed to predict the patients who might benefit from adjuvant treatment. Methods: In this first investigation of the relationship between metabolic reprogramming and recurrence in stage I LUAD, we developed a recurrence-associated metabolic signature (RAMS). This RAMS was based on metabolism-associated genes to predict cancer relapse and overall prognosis of patients with stage I LUAD. The clinical significance and immune landscapes of the signature were comprehensively analyzed. Results: Based on a gene expression profile from the GSE31210 database, functional enrichment analysis revealed a significant difference in metabolic reprogramming that distinguished patients with stage I LUAD with relapse from those without relapse. We then identified a metabolic signature (i.e., RAMS) represented by two genes (ACADM and RPS8) significantly related to recurrence-free survival and overall survival times of patients with stage I LUAD using transcriptome data analysis of a training set. The training set was well-validated in a test set. The discriminatory power of the two-gene metabolic signature was further validated using protein values in an additional independent cohort. The results indicated a clear association between a high-risk score and a very poor patient prognosis. Stratification analysis and multivariate Cox regression analysis revealed that the RAMS was an independent prognostic factor. We also found that risk score was positively correlated with inflammatory response, the antigen-presenting process, and the expression levels of many immunosuppressive checkpoint molecules (e.g., PD-L1, PD-L2, B7-H3, galectin-9, and FGL-1). These results suggested that high-risk patients had immune response suppression. Further analysis revealed that anti-PD-1/PD-L1 immunotherapy did not have significant benefits for high-risk patients. However, they could respond better to chemotherapy. Conclusion: This study was the first to highlight the relationship between metabolic reprogramming and recurrence in stage I LUAD and develop a clinically feasible signature. This signature may be a powerful prognostic tool and help further optimize the cancer therapy paradigm. Citation Format: Chengming Liu, Nan Sun, Jie He. A novel recurrence-associated metabolic prognostic model for risk stratification and therapeutic responses prediction in patients with stage I lung adenocarcinoma [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 772.
Abstract LB100: Pemetrexed disodium heptahydrate and cisplatin have distinctive growth inhibitory effects in monotherapy and combination therapy on A549 cells
Authors: Md Mohiuddin, Hideharu Kimura, Takashi Sone, Satoshi Watanabe, Hiroki Matsuoka, Keigo Saeki, Nanao Terada, Miki Abo, Kazuo Kasahara
Journal: Cancer Research (2021)

Abstract Background: Cisplatin combined with pemetrexed disodium heptahydrate (pemetrexed) is considered the standard treatment for patients with advanced, non-squamous, non-small-cell lung cancer (NSCLC). However, its individual growth inhibitory effects on KRAS-dependent A549 human lung cancer cells as monotherapy and combination therapy are not well understood. The aim of this study was to compare the effects of cisplatin (CDDP) and pemetrexed (PEM) on A549 cells as monotherapy and combination therapy.Methods: For in vitro studies, A549 cells were exposed to cisplatin and pemetrexed as monotherapy and combination therapy for 72 h. The results were then evaluated by a cell viability assay, apoptosis assay, ROS assay, TUNEL assay and Western blotting.Results: Our results revealed that cisplatin monotherapy was the most potent growth inhibitor; cisplatin plus pemetrexed combination therapy had an intermediate effect; and pemetrexed monotherapy induced a minimal growth inhibitory effect in the A549 cell line, which was observed by the inhibition of the RAS/RAF/MEK/ERK signaling pathway. Furthermore, apoptotic effects were examined according to ROS-mediated DNA damage and increased levels of cleaved caspase-3, cleaved caspase-9 and cleaved PARP. Interestingly, cisplatin monotherapy was the primary eliminator of cellular senescence; combination therapy with cisplatin plus pemetrexed had an intermediate eliminator effect, while pemetrexed monotherapy increased cellular senescence in A549 cells, which was assessed by the expression of the β-galactosidase protein. The results of Western blotting of proteins in the AMPK/mTOR signaling pathway indicated that the highest inducer of autophagy was pemetrexed monotherapy, while combination therapy with cisplatin plus pemetrexed had an intermediate inhibitory effect on autophagy. Cisplatin monotherapy showed the strongest autophagy inhibitory activity.Conclusion: In light of these findings, cisplatin monotherapy showed the most potent anticancer effects, suggesting that cisplatin monotherapy may be more effective than pemetrexed monotherapy or cisplatin plus pemetrexed combination therapy in A549 cells. Citation Format: Md Mohiuddin, Hideharu Kimura, Takashi Sone, Satoshi Watanabe, Hiroki Matsuoka, Keigo Saeki, Nanao Terada, Miki Abo, Kazuo Kasahara. Pemetrexed disodium heptahydrate and cisplatin have distinctive growth inhibitory effects in monotherapy and combination therapy on A549 cells [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 LB100.
Abstract 797: Cancers of unknown primary: A descriptive study in the U.S. military health system
Authors: Julie A. Bytnar, Jie Lin, Joel T. Moncur, Craig D. Shriver, Kangmin Zhu
Journal: Cancer Research (2021)

Abstract Background: Cancers of unknown primary (CUP) are defined as histologically confirmed metastatic cancers that do not have an identified primary site of origin despite an appropriate diagnostic work-up. It is known that accessibility to and quality of medical care are associated with cancer diagnosis. This study aimed to describe the demographic, histologic, and temporal trend characteristics of CUP patients in the Military Health System (MHS), which provides universal healthcare access. Methods: The data were obtained from the Department of Defense (DoD)'s Automated Tumor Registry (ACTUR) which collects cancer data from beneficiaries who were diagnosed or received treatment in the (MHS). We described the demographic and histologic distributions in CUP patients aged 18 or older diagnosed from 1987-2013. We calculated the proportion of CUP patients among all metastatic cancers and the most common histologic categories of those tumors. We then evaluated whether the proportion of histologic types changed over time. Results: CUP comprised 15.1% of all metastatic cancers in ACTUR during the study period. The majority of CUP within ACTUR was well and moderately differentiated adenocarcinoma (51.3%) and poorly differentiated carcinomas (23.2%) followed by squamous cell carcinomas (12.5%). The percentages of CUP among metastasized cancers of the same histologic category ranged 12-15% for well and moderately differentiated adenocarcinomas, squamous cell, and poorly differentiated carcinomas, and 41-46% for malignant neuroendocrine carcinomas and undifferentiated neoplasms. However, the percentages varied by sex, race, and age for certain pathologies. The proportion of CUP patients among all metastatic cancer patients has steadily declined from 22.4% to 8.3% from 1987 to 2013. Conclusion: The proportion and trends of CUP in the MHS were generally consistent with other descriptive CUP studies. This study provides a description of CUP in a healthcare system with universal access and provides a foundation for future studies on CUP. Citation Format: Julie A. Bytnar, Jie Lin, Joel T. Moncur, Craig D. Shriver, Kangmin Zhu. Cancers of unknown primary: A descriptive study in the U.S. military health system [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 797.
P-99 Circulating RNA detection, circulating tumor cells count, and molecular tumor profiling in a cohort of untreated metastatic colorectal cancer: A prospective multicenter ancillary study to the randomized VISNÚ trials
Authors: M. Valladares-Ayerbes, M. Toledano Fonseca, J. Vieitez de Prado, E. Inga-Saavedra, S. Gil, B. Graña Suarez, B. García-Paredes, A. Salud, F. Rivera Herrero, M. Salgado Fernandez, P. García-Alfonso, R. López-López, R. Ferreiro Monteagudo, J. Sastre, E. Diaz-Rubio, E. Aranda
Journal: Annals of Oncology (2021)
Abstract 2015: Interplay of the pH regulator, carbonic anhydrase IX and the glutamine transporter, ASCT2 in hypoxic tumor microenvironment
Authors: Geetha Venkateswaran, Shawn Chafe, Shannon Awrey, Oksana Nemirovsky, Shoukat Dedhar
Journal: Cancer Research (2021)

Abstract Solid tumors are characterized by poor vasculature, thereby causing insufficient oxygen and nutrient supply within the tumor. To thrive in such conditions, hypoxic tumor cells stimulate the expression of nutrient transporters to support cell metabolism and pH regulators to buffer the intracellular pH changes caused by metabolic by-products. Carbonic Anhydrase IX (CAIX) is a membrane-bound enzyme that plays a vital role in the pH regulation of hypoxic tumor cells. CAIX is highly expressed in several solid tumors, and is an indicator of poor prognosis and response to therapy. Although the importance of CAIX's role in mediating tumor progression is well-known, the underlying mechanism remains unclear. To identify the interactors of CAIX in the hypoxic tumor microenvironment, we performed a proteomic analysis using proximity dependent biotin identification (BioID) and found the Alanaine, Serine, Cysteine transporter (ASCT2) to be a high confidence interactor of CAIX from this analysis. ASCT2, which predominantly acts as a glutamine transporter is upregulated in several cancers and is shown to support tumor growth by facilitating increased glutamine uptake. In this study, using a panel of solid tumor cell lines, we validate the interaction of CAIX with ASCT2 in the hypoxic microenvironment. Functionally, loss of CAIX causes an increased glutamine uptake via ASCT2 and an increased capacity of cells to utilize glutamine for mitochondrial respiration. Concomitantly, ROS and glutathione (GSH) levels also increase upon CAIX inhibition. Cytotoxicity studies show a robust cell death in the absence of glutamine, following treatment with the CAIX/XII small molecule inhibitor SLC-0111. A similar effect on cell death is observed by blocking glutamine metabolism using inhibitors such as V-9302 (ASCT2 inhibitor) or CB-839 (Glutaminase-1 inhibitor) with SLC-0111. Furthermore, blocking GSH synthesis using BSO (Glutamylcysteine synthatase inhibitor) with SLC-0111 causes significant cell death. These results suggest that CAIX depletion causes increased cellular stress and to overcome this, cells increase glutamine uptake in part for GSH synthesis. In summary, we show that CAIX and ASCT2 coordinate their functions in hypoxic cancer cells to support tumor growth, and co-targeting them could be beneficial in treating solid tumors. Citation Format: Geetha Venkateswaran, Shawn Chafe, Shannon Awrey, Oksana Nemirovsky, Shoukat Dedhar. Interplay of the pH regulator, carbonic anhydrase IX and the glutamine transporter, ASCT2 in hypoxic tumor microenvironment [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 2015.
Over 60s in England could pay for prescriptions until retirement, says government consultation
Authors: Abi Rimmer
Journal: BMJ (2021)

The government is consulting on plans to align the upper age exemption for NHS prescription charges with the state pension age in England.

Currently, people receive free prescriptions when they turn 60 in England, whereas the state pension age is 66.

The consultation, published on 1 July,1 said that owing to the default retirement age being abolished, “many people in the age range 60 to 65 are and can remain in employment and be economically active and more able to meet the cost of their …
Routine urinary biochemistry does not accurately predict stone type nor recurrence in kidney stone formers: A multi-centre, multi-model, externally validated machine-learning study
Authors: R. Geraghty, I. Wilson, E. Olinger, P. Cook, S. Troup, D. Kennedy, A. Rogers, M. Shaw, B. Somani, N. Dhayat, D. Fuster, J. Sayer
Journal: European Urology (2021)
急性左心室圧過負荷時における僧帽弁複合体ジオメトリの動態:リアルタイム3D心エコー図の使用によるin vivo実験研究
Authors: Yamada Ryotaro, Watanabe Nozomi, Kume Teruyoshi, Neishi Yoji, Kawamoto Takahiro, Toyota Eiji, Okahashi Noriko, Saito ken, Okura Hiroyuki, Yoshida Kiyoshi
Journal: Circulation (2007)
Science, not speculation, is essential to determine how SARS-CoV-2 reached humans
Authors: Charles H Calisher, Dennis Carroll, Rita Colwell, Ronald B Corley, Peter Daszak, Christian Drosten, Luis Enjuanes, Jeremy Farrar, Hume Field, Josie Golding, Alexander E Gorbalenya, Bart Haagmans, James M Hughes, Gerald T Keusch, Sai Kit Lam, Juan Lubroth, John S Mackenzie, Larry Madoff, Jonna Keener Mazet, Stanley M Perlman, Leo Poon, Linda Saif, Kanta Subbarao, Michael Turner
Journal: The Lancet (2021)
Cellular and molecular mechanisms of perineural invasion of pancreatic ductal adenocarcinoma
Authors: Jingbo Li, Rui Kang, Daolin Tang
Journal: Cancer Communications (2021)

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignant disease with a unique tumor microenvironment surrounded by an interlaced network of cancer and noncancerous cells. Recent works have revealed that the dynamic interaction between cancer cells and neuronal cells leads to perineural invasion (PNI), a clinical pathological feature of PDAC. The formation and function of PNI are dually regulated by molecular (e.g., involving neurotrophins, cytokines, chemokines, and neurotransmitters), metabolic (e.g., serine metabolism), and cellular mechanisms (e.g., involving Schwann cells, stromal cells, T cells, and macrophages). Such integrated mechanisms of PNI not only support tumor development, growth, invasion, and metastasis but also mediate the formation of pain, all of which are closely related to poor disease prognosis in PDAC. This review details the modulation, signaling pathways, detection, and clinical relevance of PNI and highlights the opportunities for further exploration that may benefit PDAC patients.