tbuckley/cabot-search huggingface dataset:
Abstract 843: Coffee consumption and risk of renal cell carcinoma: A meta-analysis of cohort evidence
Authors: Jongeun Rhee, Rachel Lim, Mark P. Purdue
Journal: Cancer Research (2021)

Abstract Background: Coffee consumption has been associated with a reduced risk of some cancers, although for renal cell carcinoma (RCC) the evidence is inconclusive. Several cohort analyses investigating coffee intake and RCC have been conducted, although most have been limited by small case numbers. To summarize the cohort evidence of this relationship, we conducted a meta-analysis. Methods: A literature search was performed in PubMed, Embase and The Cochrane Library for all studies published up to May 2020 using the key words “cancer”, “tumor”, “carcinoma”, “malignant neoplasm”, “renal cell carcinoma”, “kidney cancer”, “renal cancer” “coffee”, “caffeine” and “beverages”. Additionally, the reference lists of all retrieved articles and previous meta-analysis studies were checked to identify additional studies. From our collection of full-text articles (n=7219) we excluded irrelevant topic articles (n=7125), non-English articles (n=2), systematic reviews or editorial letter (n=46), relevant articles not reporting measure of association (n=9), case-control studies (n=27). Following these exclusions, 10 cohort studies remained. Meta-analyses using a random effects model were conducted for relative risks (RRs) contrasting the highest vs lowest level of coffee intake per day. In addition, meta-analyses were conducted for reported sex-specific findings as well as findings restricted to non-smokers. Between-study heterogeneity was assessed using Cochran Q-statistic and quantified by Higgins I2 statistic. Results: In a meta-analysis of the 10 identified studies, we found a summary RR of 0.88 (95% CI 0.78-0.99) relating the highest study category of coffee intake (vs. the lowest category or non-drinkers) and renal cancer risk, with no significant between-study heterogeneity observed (I2=35%, p = 0.13). The summary RR was comparable for men and women (0.89 and 0.85 respectively). A slightly stronger inverse association was observed among non-smokers (RR 0.78, 95% CI 0.59-1.03), although with moderate evidence of study heterogeneity (I2=62%, p = 0.07). Conclusions: In this meta-analysis of cohort evidence, we observed overall evidence suggestive of a weak inverse association between higher coffee consumption and lower renal cancer risk. Citation Format: Jongeun Rhee, Rachel Lim, Mark P. Purdue. Coffee consumption and risk of renal cell carcinoma: A meta-analysis of cohort evidence [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 843.
Robot Assisted Partial Nephrectomy using Intra-Arterial Renal Hypothermia for Highly Complex Endophytic or Hilar Tumors: Case series and Description of Surgical Technique
Authors: P. De Backer, J. Vangeneugden, C. Van Praet, M. Lejoly, S. Vermijs, C. Vanpeteghem, K. Decaestecker
Journal: European Urology (2021)
Abstract 2151: Neuroendocrine cancer cells have changed HOX code during trans-differentiation
Authors: Siyuan Cheng, Shu Yang, Yingli Shi, Runhua Shi, Yunshin Yeh, Xiuping Yu
Journal: Cancer Research (2021)

Abstract Background: HOX genes encode Homeobox-containing proteins. There are 39 HOX genes organized into 4 clusters in human. The nested and partially overlapping expression of HOX genes in an anatomic region can determine its tissue specificity, which is termed as “HOX code”. In this study, we examined the expression of HOX genes in neuroendocrine prostate cancer (NEPCa), an aggressive subtype prostate cancer that arises from prostate adenocarcinoma (AdPCa) trough trans-differentiation. Methods: The HOX genes expression data were extracted from Cancer Cell Line Encyclopedia (CCLE) dataset. All in silico analysis were performed by using R language. Immunohistochemistry (IHC), dual immunofluorescence staining, Western blot and RT-qPCR were conducted to access the expression of HOXs. Results: Using the HOXs' mRNA expression data from CCLE, we generated HOX codes for 25 different types of tissues. These HOX codes were validated in TCGA pan cancer. By calculating the Pearson correlation, we were able to use 9 HOX codes including prostatic HOX code to identify the tissue origins of the cancer samples. Further, we found that in prostate cancer, the NEPCa samples have lost prostatic HOX code while majority of the AdPCa samples maintain the prostatic HOX code. The expression of HOXB13, the most prominent HOX expressed in prostatic tissues, was increased in AdPCa along with PCa progression but was decreased in NEPCa. Similarly, we found that in breast cancer, a sub-group of samples correlated well with the HOX code of mammary gland, but the rest did not. By comparing the differentially expressed genes in these two subgroups of samples, we found that the neuroendocrine markers including CHGA, CHGB and SYP were higher in HOX code-negative samples compared with HOX code-positive ones. Additionally, we observed a similar phenomenon in colorectal cancer samples: The expression of neurogenesis genes were enriched in HOX code-negative subgroup. Conclusions: 1) The expression of HOXB13 is decreased in NEPCa. 2) NEPCa has changed HOX code, suggesting the loss of prostatic identity in these samples. 3) The association of neuroendocrine phenotype with the changes in HOX code is not limited to prostate cancer but also is observed in other types of cancer. Significance: The HOX codes we established can be used in pan cancer research to identify the tissue origins of cancer samples and to study the trans-differentiation of cancer cells. Funding: This study is supported by: The LSUHS Office of Research SEED awards, NIH R01 CA226285 and Feist-Weiller Cancer Center. Citation Format: Siyuan Cheng, Shu Yang, Yingli Shi, Runhua Shi, Yunshin Yeh, Xiuping Yu. Neuroendocrine cancer cells have changed HOX code during trans-differentiation [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 2151.
Incorrectly analysing stratified and minimised trials may lead to wrongfully rejecting superiority of interventions
Authors: Reinier Cornelis Anthonius van Linschoten, Rachel West, Desirée van Noord, Nikki van Leeuwen
Journal: Gut (2021)

It is with great interest that we read the report of Yoshida et al 1 on the effect of second-generation narrow band imaging compared to white light imaging on detecting early gastric cancer in high-risk patients. The trial was expertly designed with a large patient population and, although superiority of narrow band imaging could not be proven, has important implications for further research on this topic. However, a significant issue concerning the analyses attracted our interest and we would like to comment on it.

The primary outcome, the difference in proportion of patients in whom early gastric cancer was diagnosed, failed to reach statistical significance (p=0.412). This difference in proportions was tested for significance using Fisher’s exact test. This might not have been the proper method for analysis, as patients in the study were randomised using minimisation with a random component, stratified by institution, age and indication of endoscopy.

Imbalance of risk factors between treatment and control arms can occur by chance …
Impact of decipher biopsy testing on clinical outcomes in localized prostate cancer in a prospective statewide collaborative
Authors: R. Vince, J. Qi, F. Felix, S. Linsell, A. Johnson, S. Shetty, P. Hurley, D. Miller, A. George, K. Ghani, F. Sun, M. Seymore, R. Dess, W. Jackson, M. Schipper, D. Spratt, T. Morgan
Journal: European Urology (2021)
Severity of COVID-19 infection in prostate cancer patients and effect of ADT on disease presentation
Authors: C. García Fuentes, E. Jiménez Alcaide, V. Hernández, E. De La Pena Zarzuelo, A. Guijarro Cascales, A. Castro Fajardo, E. Pérez-Fernández, C. Llorente
Journal: European Urology (2021)
Quick-start infrastructure for untargeted metabolomics analysis in GNPS
Authors: Tiago F. Leao, Chase M. Clark, Anelize Bauermeister, Emmanuel O. Elijah, Emily C. Gentry, Makhai Husband, Michelli F. Oliveira, Nuno Bandeira, Mingxun Wang, Pieter C. Dorrestein
Journal: Nature Metabolism (2021)
Abstract 1713: Novel, potent and orally bioavailable small molecule CD73 inhibitors for cancer immunotherapy
Authors: Chandregowda Venkateshappa, Kishore Narayanan, Prasath Kothandaraman, Garima Priyadarshani, Rashmi Nair, Megha Goyal, Vijay Kamal Ahuja, Sagar Dadhania, AB Aravind, DS Samiulla, Girish Daginakkatte, Thomas Antony, Kavitha Nellore, Sunil Panigrahi, Dinesh Chikkanna, Susanta Samajdar, Murali Ramachandra
Journal: Cancer Research (2021)

Abstract CD73 is a cell surface ectoenzyme, which is overexpressed in many types of human and mouse cancers. CD73 is the primary enzymatic producer of immunosuppressive adenosine in the tumor microenvironment, and high CD73 expression is associated with significantly poorer prognosis in several tumor types. Inhibition of either adenosine generation or signaling by inhibiting CD73 have been shown to be effective therapeutic approaches. Here we sought to discover and develop novel and orally bioavailable small molecule inhibitors that target CD73. Aurigene's non-nucleotide small molecule exhibit potent inhibition of CD73 in respective biochemical and cellular assays. High potency translated into rescue of AMP induced repression of IFN-Υ and IL-2 in human PBMCs. Lead compounds exhibited desirable drug-like properties including solubility, Caco2 permeability, lack of CYP inhibition and excellent oral pharmacokinetic exposure. In summary, we have identified small molecule inhibitors with good drug like properties, which showed good in vitro potency and excellent PK. Evaluation of these lead compounds in syngeneic tumor model along with in vivo toxicity studies are currently under way. Citation Format: Chandregowda Venkateshappa, Kishore Narayanan, Prasath Kothandaraman, Garima Priyadarshani, Rashmi Nair, Megha Goyal, Vijay Kamal Ahuja, Sagar Dadhania, AB Aravind, DS Samiulla, Girish Daginakkatte, Thomas Antony, Kavitha Nellore, Sunil Panigrahi, Dinesh Chikkanna, Susanta Samajdar, Murali Ramachandra. Novel, potent and orally bioavailable small molecule CD73 inhibitors for cancer immunotherapy [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 1713.
Fully Automated Gross Tumor Volume Delineation From PET in Head and Neck Cancer Using Deep Learning Algorithms
Authors: Isaac Shiri, Hossein Arabi, Amirhossein Sanaat, Elnaz Jenabi, Minerva Becker, Habib Zaidi
Journal: Clinical Nuclear Medicine (2021)

Purpose The availability of automated, accurate, and robust gross tumor volume (GTV) segmentation algorithms is critical for the management of head and neck cancer (HNC) patients. In this work, we evaluated 3 state-of-the-art deep learning algorithms combined with 8 different loss functions for PET image segmentation using a comprehensive training set and evaluated its performance on an external validation set of HNC patients. Patients and Methods 18 F-FDG PET/CT images of 470 patients presenting with HNC on which manually defined GTVs serving as standard of reference were used for training (340 patients), evaluation (30 patients), and testing (100 patients from different centers) of these algorithms. PET image intensity was converted to SUVs and normalized in the range (0–1) using the SUV max of the whole data set. PET images were cropped to 12 × 12 × 12 cm 3 subvolumes using isotropic voxel spacing of 3 × 3 × 3 mm 3 containing the whole tumor and neighboring background including lymph nodes. We used different approaches for data augmentation, including rotation (−15 degrees, +15 degrees), scaling (−20%, 20%), random flipping (3 axes), and elastic deformation (sigma = 1 and proportion to deform = 0.7) to increase the number of training sets. Three state-of-the-art networks, including Dense-VNet, NN-UNet, and Res-Net, with 8 different loss functions, including Dice, generalized Wasserstein Dice loss, Dice plus XEnt loss, generalized Dice loss, cross-entropy, sensitivity-specificity, and Tversky, were used. Overall, 28 different networks were built. Standard image segmentation metrics, including Dice similarity, image-derived PET metrics, first-order, and shape radiomic features, were used for performance assessment of these algorithms. Results The best results in terms of Dice coefficient (mean ± SD) were achieved by cross-entropy for Res-Net (0.86 ± 0.05; 95% confidence interval [CI], 0.85–0.87), Dense-VNet (0.85 ± 0.058; 95% CI, 0.84–0.86), and Dice plus XEnt for NN-UNet (0.87 ± 0.05; 95% CI, 0.86–0.88). The difference between the 3 networks was not statistically significant ( P &gt; 0.05). The percent relative error (RE%) of SUV max quantification was less than 5% in networks with a Dice coefficient more than 0.84, whereas a lower RE% (0.41%) was achieved by Res-Net with cross-entropy loss. For maximum 3-dimensional diameter and sphericity shape features, all networks achieved a RE ≤ 5% and ≤10%, respectively, reflecting a small variability. Conclusions Deep learning algorithms exhibited promising performance for automated GTV delineation on HNC PET images. Different loss functions performed competitively when using different networks and cross-entropy for Res-Net, Dense-VNet, and Dice plus XEnt for NN-UNet emerged as reliable networks for GTV delineation. Caution should be exercised for clinical deployment owing to the occurrence of outliers in deep learning–based algorithms.
Abstract 1339: Investigations into rational combination approaches with ivosidenib in a mutant IDH1 acute myeloid leukemia patient-derived xenograft model
Authors: Christine Hudson, Rohini Narayanaswamy, Sebastien Ronseaux, Chris Bowden, Brandon Nicolay
Journal: Cancer Research (2021)

Abstract Background: Somatic mutations in isocitrate dehydrogenase 1 (IDH1) arise in roughly 6-10% of patients with acute myeloid leukemia (AML). These mutations lead to the production of the oncometabolite 2-hydroxyglutarate at concentrations shown to interfere with epigenetic control of gene expression, which prevents hematopoietic cell maturation. Ivosidenib (IVO; AG-120) is an oral, potent, targeted oral inhibitor of mutant IDH1 (mIDH1) and is FDA-approved for the treatment of mIDH1 relapsed/refractory AML patients and mIDH1 newly diagnosed (ND) AML in adults ≥ 75 years of age or with comorbidities precluding intensive induction chemotherapy. Methods: Currently, IVO is being investigated in combination with azacitidine (AZA) in the actively enrolling phase 3 AGILE study (NCT03173248). To support this ongoing effort, studies were undertaken to explore the IVO + AZA combination in a mIDH1 AML patient-derived xenograft (PDX) model in vivo. These studies examined the timing of IVO + AZA treatment with respect to disease burden control and durability in mice inoculated with a disseminated mIDH1 AML PDX model, both as a frontline treatment as well as in a maintenance therapy setting following either venetoclax (VEN) + AZA, or VEN + AZA + IVO. In addition, the studies examined the utility of combining IVO + VEN as an alternative frontline treatment approach in the same preclinical mIDH1 AML PDX disseminated model. Results: The IVO + AZA combination led to a &amp;gt; 99% reduction in hCD45+ cells within the bone marrow and undetectable disease in the peripheral blood of 7/10 mice by Week 10. Similar results were observed with IVO + VEN treated animal bone marrow (99% reduction in hCD45+ cells) and undetectable disease was observed in 8/10 mice by week 10. Conclusions: Each combination was well tolerated by the mice. The observed disease control with either combination in the animals was greater than any of the three single agents alone. Ongoing follow-up xenograft studies investigating the utility of the combinations with IVO as a maintenance therapy are still ongoing and outcomes will be presented. Citation Format: Christine Hudson, Rohini Narayanaswamy, Sebastien Ronseaux, Chris Bowden, Brandon Nicolay. Investigations into rational combination approaches with ivosidenib in a mutant IDH1 acute myeloid leukemia patient-derived xenograft model [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 1339.
Abstract 213: BART cancer: A web resource for transcriptional regulators in cancer genomes
Authors: Zachary V. Thomas, Zhenjia Wang, Chongzhi Zang
Journal: Cancer Research (2021)

Abstract The goal of this study is to develop a comprehensive data resource for transcriptional regulator activities in various cancers. Dysregulation of gene expression plays an important role in cancer development. Identifying transcriptional regulators (TRs), including transcription factors and chromatin regulators, that drive the oncogenic gene expression program is a critical task in cancer research. Genomic TR profiling data from primary cancer samples are limited in the public domain. Here, we present BART Cancer, an interactive web resource database to display putative TRs that are responsible for regulating differentially expressed genes across 15 different cancer types included in The Cancer Genome Atlas (TCGA). BART Cancer integrates over 10,000 gene expression profiling RNA-seq datasets from TCGA with over 7,000 ChIP-seq datasets from the Cistrome Data Browser database and the Gene Expression Omnibus (GEO). BART Cancer uses Binding Analysis for Regulation of Transcription (BART) for predicting TRs from differentially expressed genes comparing cancer samples with normal samples for each cancer type. BART Cancer also displays the activities of over 900 TRs across cancer types, by integrating computational prediction results from BART and from the Cistrome Cancer database. Focusing on transcriptiona regulatory activities in human cancers, BART Cancer provides unique insights into epigenetics and transcriptional regulation in cancer, and is a useful data resource for genomics and cancer research communities. BART Cancer web resource can be accessed at: http://bartcancer.org. Citation Format: Zachary V. Thomas, Zhenjia Wang, Chongzhi Zang. BART cancer: A web resource for transcriptional regulators in cancer genomes [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 213.
Abstract 1967: Chaperonin-Containing TCP1 complex (CCT) promotes breast cancer by targeting key cell cycle regulators
Authors: Heba H. Ghozlan, Adrian Showalter, Annette R. Khaled
Journal: Cancer Research (2021)

Abstract CCT is a protein folding complex that interacts with known oncoproteins, but its role as a driver of oncogenesis is unknown. Elucidating interactions of CCT with cell cycle regulators could reveal the oncogenic potential of the chaperonin. CCT is multi-subunit complex composed of two stacked rings formed by eight distinct subunits (CCT1-8). While different CCT subunits are associated with cancer and other diseases, we found that the CCT2 subunit is upregulated in breast cancer and other cancers and that its expression inversely correlates with patients' overall and progression free survival. Mining datasets from TCGA revealed that amplification of CCT2 is the predominant genomic alteration occurring in cancer patients and that CCT2 is frequently co-amplified or co-expressed with other oncogenes such as MDM2, FRS2, YEATS4, and CDK4 found in the 12q13-15 amplicon. Genetic alteration of CCT2 significantly associates with worse clinical outcome for cancer patients. To investigate the functional outcomes of CCT2 overexpression in breast cancer, spheroid culture was used. A CCT2-FLAG lentiviral vector was used to transduce T47D and MCF7 luminal breast cancer cells and cells grown in ultra-low attachment plates to induce spheroid growth. Expression of CCT2 increased growth of spheroids as compared to lentiviral control cells. In contrast, CCT2 depletion impaired spheroid formation, instead causing formation of loose aggregates. CCT2 overexpression increased the proliferative potential of spheroid cells and promoted progression though the G1/S phase of the cell cycle in synchronized cells by increasing expression of cell cycle regulators like Cyclin D1, CDK2 and CDK4. After 8 days in spheroid culture, CCT2 overexpressing cancer cells resumed attachment when transferred into 2D culture conditions; these cells acquire anchorage dependent and independent growth capability, increased actin expression, and proliferated. These characteristics of CCT2 overexpressing cells may be indicative of supporting a more invasive and metastatic phenotype. In support, we discovered that, along with cell cycle genes, CCT2 overexpressed cells increased expression of MYC, suggesting the CCT2 could be a novel regulator of MYC expression. Our results contribute new knowledge on the role of CCT2 in uncontrolled breast cancer progression and proliferation by regulating cell cycle genes. The recurrent amplification of CCT2 in different cancer types along with other oncogenes like MYC, MDM2 and CDK4 support it is role as a potential oncogene and novel therapeutic target for breast cancer. Citation Format: Heba H. Ghozlan, Adrian Showalter, Annette R. Khaled. Chaperonin-Containing TCP1 complex (CCT) promotes breast cancer by targeting key cell cycle regulators [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 1967.
Assessing the association between the template of pelvic salvage lymph node dissection for node-only recurrent prostate cancer and oncological outcomes. Results of a multi-institutional series
Authors: C.A. Bravi, N. Fossati, G. Gandaglia, G. Motterle, R.J. Karnes, D. Pfister, A. Heidenreich, A. Buchner, C. Stief, G. Devos, S. Joniau, H. Van Poppel, D. Osmonov, K. Jueneman, B. Grubmuller, S. Shariat, A. Nini, A. Hiester, P. Albers, D. Tilki, M. Graefen, I.S. Gill, A. Mottrie, F. Montorsi, A. Briganti
Journal: European Urology (2021)