tbuckley/cabot-search huggingface dataset:
Abstract 3071: A method for infratentorial structures segmentation for tumor treating fields treatment planning
Authors: Yana Glozman, Reuben R. Shamir, Zeev Bomzon
Journal: Cancer Research (2021)

Abstract Introduction: Tumor treating fields (TTFields) is an FDA approved treatment for the management of glioblastoma multiform (GBM) and mesothelioma (MPM) and is associated with a significant extension to patients' survival. We have developed software to optimize the location of the TTFields transducer arrays (TAs) on GBM patients' head to maximize the field in the tumor region. To that end, we first segment the patients' head MRIs into five normal and three abnormal tissues. However, the current method for head segmentation was found to be less accurate at the infratentorial regions, mark some sinuses with cerebrospinal fluid (CSF), and does not identify the cerebellum and brain-stem. Therefore, it is assuming the infratentorial structures have the same electrical properties as in the cerebrum. Methods: We have developed a new method for segmentation of the head MRI that overcomes these limitations. As in the previous method, we have incorporated an atlas that is composed of an MRI image and tissue probability maps (TPM). The TPM assign each voxel in the atlas MRI with a value in the range of 0-1. This value reflects the probability that the specific tissue resides in that voxel. We have generated new customized TPMs for the cerebellum, brain stem and sinuses. Moreover, we have carefully revised the other TPMs to ensure best results. Last, we have incorporated these TPMs in a new atlas-based segmentation method. We have validated the method on 10 GBM patients T1w +gad head MRIs. Results: The average Dice coefficient between gold-standard and algorithms' segmentation was 68.4% (SD=11.2%) that is similar to the value observed with the current method implemented in the treatment-planning software (67.8%; SD=10.6%). However, the new method presented here extends the current method with the cerebellum (average Dice = 84%) and brainstem (average Dice = 67%). Moreover, the sinuses are marked with air, and erroneous CSF segments in the sinuses were removed. Conclusions: We have presented a novel method for the segmentation of the head that facilitates accurate infratentorial and supratentorial structures' segmentation. Moreover, the method eliminates erroneous CSF segmentation in the sinuses. These improvements pave the way for TTFields planning for infratentorial tumors. Citation Format: Yana Glozman, Reuben R. Shamir, Zeev Bomzon. A method for infratentorial structures segmentation for tumor treating fields treatment planning [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 3071.
Opportunities and obstacles of translating elite sport research to public health
Authors: Gregoire P Millet, Stephen Seiler, Guillaume Y Millet
Journal: British Journal of Sports Medicine (2021)

In a recent editorial, Thornton et al 1 argued that ‘Like folklore hero Robin Hood, we - sport and exercise medicine (SEM) scientists and practitioners - can draw on the opportunity and expertise gained by working with the elite few and apply it for the benefit of many ’ . We applaud this positive point of view. It was, however, supported by only one example—the successful ‘11 for health’ programme. That sport science-driven knowledge and innovation developed from elite sport translates or ‘scales down’ (ie, ‘Formula-1 circus to my garage’ paradigm) remains debatable. The goals may be similar for elite athletes and general or clinical populations, that is, optimising training impact and minimising negative effects (injuries, chronic fatigue/overtraining) but we argue that knowledge developed by sport scientists and practitioners working with elite athletes cannot be directly translated to population health without careful analysis and adaptation. Athletes are not immune from diseases or co-morbidities,2 so ‘elite athlete’ and ‘non-healthy population’ categories overlap. Moreover, treatment may be more challenging in elite athletes due to added stress from exercise or antidoping regulations.3

By presenting …
Developing Drugs for Prevention of Chemotherapy-Induced Nausea and Vomiting: Draft Guidance from the FDA
Authors: Erica Lyons, Charles Line, Jessica J. Lee
Journal: Clinical Cancer Research (2021)

The administration of preventative therapy for chemotherapy-induced nausea and vomiting (CINV) is an essential component of the treatment plan for many patients with cancer. In May 2021, the FDA issued a draft guidance for industry to facilitate the clinical development of drugs for the prevention of CINV in adults. FDA guidance has a vital role in the regulatory dialogue between the Agency and external stakeholders. Sharing the FDA's current recommended approach can expedite drug development and ultimately the availability of safe and effective therapies to patients in need. In addition, guidance documents may be leveraged to facilitate communication between regulatory agencies, the academic community, patient advocacy groups, and the pharmaceutical industry. The draft guidance for industry Chemotherapy-Induced Nausea and Vomiting: Developing Drugs for Prevention (May 2021) outlines the FDA's current recommendations regarding clinical development programs for drugs for the prevention of CINV and the required attributes of patients for enrollment, aspects of trial design, and efficacy assessments. This article provides an overview of the recommendations contained in the draft guidance.
Healthcare Resource Utilization (HCRU) and treatment patterns in men with Erectile Dysfunction (ED) and Benign Prostatic Hyperplasia-associated Lower Urinary Tract Symptoms (BPH-LUTS) in the United States: A retrospective database study
Authors: T. Hassan, I. Goldstein, K.H. Zou, V. Divino, M. Dekoven, J.S. Imperato, V.R. Anupindi, J.Z. Li
Journal: European Urology (2021)
Evaluation for efficacy of repeat transurethral resection of bladder tumor at Ta high grade bladder cancer
Authors: S.H. Yoo, H.S. Yoon, G.H. Jung, D.H. Park, J.G. Suh, Y.S. Kho, H.D. Yuk, C.W. Jeong, C. Kwak, H.H. Kim, J.H. Ku
Journal: European Urology (2021)
Chronic Kidney Disease Testing Among Primary Care Patients With Type 2 Diabetes Across 24 U.S. Health Care Organizations
Authors: Nikita Stempniewicz, Joseph A. Vassalotti, John K. Cuddeback, Elizabeth Ciemins, Amy Storfer-Isser, Yingying Sang, Kunihiro Matsushita, Shoshana H. Ballew, Alex R. Chang, Andrew S. Levey, Robert A. Bailey, Jesse Fishman, Josef Coresh
Journal: Diabetes Care (2021)

Clinical guidelines for people with diabetes recommend chronic kidney disease (CKD) testing at least annually using estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (uACR). We aimed to understand CKD testing among people with type 2 diabetes in the U.S.Electronic health record data were analyzed from 513,165 adults with type 2 diabetes receiving primary care from 24 health care organizations and 1,164 clinical practice sites. We assessed the percentage of patients with both one or more eGFRs and one or more uACRs and each test individually in the 1, 2, and 3 years ending September 2019 by health care organization and clinical practice site. Elevated albuminuria was defined as uACR ≥30 mg/g.The 1-year median testing rate across organizations was 51.6% for both uACR and eGFR, 89.5% for eGFR, and 52.9% for uACR. uACR testing varied (10th-90th percentile) from 44.7 to 63.3% across organizations and from 13.3 to 75.4% across sites. Over 3 years, the median testing rate for uACR across organizations was 73.7%. Overall, the prevalence of detected elevated albuminuria was 15%. The average prevalence of detected elevated albuminuria increased linearly with uACR testing rates at sites, with estimated prevalence of 6%, 15%, and 30% at uACR testing rates of 20%, 50%, and 100%, respectively.While eGFR testing rates are uniformly high among people with type 2 diabetes, testing rates for uACR are suboptimal and highly variable across and within the organizations examined. Guideline-recommended uACR testing should increase detection of CKD.
Prognostic variability among high-risk prostate cancer patients with pN1 disease according to the primary tumour pathologic features after radical prostatectomy
Authors: D. Milonas, L. Tosco, A.L. Laenen, A.B. Briganti, P.G. Gontero, M.G. Graefen, P. Chlosta, C.G. Gratzke, G.M. Marchioro, R. Sanchez-Salas, B.T. Tombal, H. Van Der Poel, H. Van Poppel, R.J. Karnes, M.S. Spahn, G.DM. De Meerleer, S.J. Joniau
Journal: European Urology (2021)
A human three-dimensional neural-perivascular ‘assembloid’ promotes astrocytic development and enables modeling of SARS-CoV-2 neuropathology
Authors: Lu Wang, David Sievert, Alex E. Clark, Sangmoon Lee, Hannah Federman, Benjamin D. Gastfriend, Eric V. Shusta, Sean P. Palecek, Aaron F. Carlin, Joseph G. Gleeson
Journal: Nature Medicine (2021)
Abstract 2902: Beneficial effect of vactosertib combined with nal-IRI5-FU/LV in pancreatic cancer treatment
Authors: Eunji Hong, Sujin Park, Akira Oshima, Jinsun Heo, Jinah Park, Jihee Lee, Kyoungwha Pang, Songee Han, Hyeyeon Park, Seong-Jin Kim
Journal: Cancer Research (2021)

Abstract Pancreatic cancer is one of leading causes of cancer-related mortality in the world. Treatment of pancreatic cancer is difficult due to aggressiveness, distal metastasis, and genetic and epigenetic alterations. Especially, TGF-β is highly expressed in the pancreatic cancer patients, and it leads aggressive tumor metastasis. Regulation of TGF-β signaling is essential for controlling tumor progression and metastasis because TGF-β is involved in cell proliferation, epithelial-to-mesenchymal transition, angiogenesis, metastasis, and immune responses in cancer. Therefore, inhibition of TGF-β signaling may be the key concept of effective chemotherapies for metastatic pancreatic cancer. Recently, nanoliposomal iriotecan (nal-IRI), 5-flourouracil (5-FU) and leucovorin (LV) adjuvant therapy has been applied for pancreatic cancer patients' treatment. Vactosertib, one of the leading TGF-β inhibitor, has been used for clinical trials in many chemotherapy strategies. In this study, we investigated the combination treatment effect of nal-IRI/5-FU/LV and vactosertib on pancreatic cancer in syngeneic orthotopic pancreatic mouse model. The combination treatment significantly increased survival rate compare with control or single treatment of vactosertib or nal-IRI/5-FU/LV. In the histological analysis showed that cancer cell invasion to surrounding tissues was markedly reduced in vactosertib and combination treatment groups. In the RNA-sequencing analysis of tumor RNA, the apoptotic process are positively regulated in vactosertib plus nal-IRI/5-FU/LV group. Furthermore, we found the up-regulated differentially expressed gene (DEG), CCDC80, involved in cell migration, invasion and apoptosis. We ectopically overexpressed CCDC80 on pancreatic cancer cell lines and demonstrated the tumor suppressive role of CCDC80. In conclusion, the combination treatment with vactosertib with nal-IRI/5-FU/LV improved pancreatic cancer survival by inhibiting tumor invasion and inducing apoptosis. These results indicate that combination therapy can be applied to clinical trials in pancreatic cancer patient. This study supported by KHIDI grant (HI14C2640) and National R&amp;D Program for Cancer Control, Ministry for Health and Welfare, Republic of Korea (HA17C0037). Citation Format: Eunji Hong, Sujin Park, Akira Oshima, Jinsun Heo, Jinah Park, Jihee Lee, Kyoungwha Pang, Songee Han, Hyeyeon Park, Seong-Jin Kim. Beneficial effect of vactosertib combined with nal-IRI5-FU/LV in pancreatic cancer treatment [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 2902.
Abstract 2452: Metformin administration in hypoglycemia compromises cancer cell viability in glioblastoma initiating cells
Authors: Francesca Cianci, Riccardo Cazzoli, Ivan Verduci, Saverio Minucci, Michele Mazzanti
Journal: Cancer Research (2021)

Abstract Cancer cells show higher energy and biomolecules requirements than healthy cells, making the targeting of cancer metabolic dysfunctions an appealing therapeutic approach. Unfortunately, tackling the tumor metabolism is a daunting task, due to the ability of cancer cells to re-organize their metabolism switching between glycolysis and oxidative phosphorylation. Cancer metabolic plasticity and re-programming is partially supported by altered ionic channels expression and activity, our laboratory has described Chloride Intracellular Channel 1 (CLIC1) as a marker of malignancy in tumor cells and a possible therapeutic target. CLIC1 is a metamorphic protein able to switch between cytoplasmic and transmembrane forms (tmCLIC1), the latter characterized by chloride conductance. TmCLIC1 was found to be overexpressed in several solid tumors where supports cancer proliferation and growth, while it is mainly absent in healthy cells. Recently, it has been demonstrated that tmCLIC1 activity is affected by biguanide compounds, in particular metformin. Metformin was recently repurposed as an anticancer drug with unclear mechanisms. We demonstrated that in hypoglycemia, metformin displays increased toxic effect on cancer cells, inducing apoptosis. Metformin inhibits Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A), and hypoglycemia upregulates PP2A subunit B56δ targeting the Glycogen Synthase Kinase 3 Beta (GSK3b). Metformin treatment in combination with hypoglycemia leads to de-phosphorylation of GSK3b protein resulting in degradation of induced myeloid leukemia cell differentiation protein (MCL-1), a pro-survival protein, and cell death (Elgendy et al., Cancer Cell 2019). In primary glioblastoma cell lines enriched in tumor-initiating-cells (GSCs), metformin has proven to be effective in reducing cell growth without affecting viability (Gritti et al., Oncotarget 2014). Here, we are going to show studies trying to establish whether CLIC1 is a component of the established PP2A-mediated signaling network. Our work aims to clarify metformin molecular mechanism of action and to assess a new potential therapeutic approach for solid tumors in which tmCLIC1 is found to be overexpressed. Citation Format: Francesca Cianci, Riccardo Cazzoli, Ivan Verduci, Saverio Minucci, Michele Mazzanti. Metformin administration in hypoglycemia compromises cancer cell viability in glioblastoma initiating 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 2452.
Abstract 280: Sub-30-nm capsules for drug delivery
Authors: Xiaowei Ma, Ping Zhang, Chao Cui, Chang-Chun Ling, Lina Cui
Journal: Cancer Research (2021)

Abstract Systemic treatment of cancer using long-circulating nanomedicines is promising due to their passive tumor targeting ability to achieve higher and more selective accumulation in tumors with irregular vascularization, a phenomenon known as extended permeation and retention (EPR) effect.1,2 Clinical use of nanometer-sized carriers, such as Doxil and Abraxane, to deliver chemotherapeutics to solid tumors is proven effective in highly vascularized tumors such as breast cancer, ovarian cancer, multiple myeloma, and Kaposi's sarcoma.3-5 Most nanomedicines that are being developed or approved so far have a diameter of around 100-200 nm for prolonged retention in highly angiogenic and densely vascularized tumors,6 however, they suffer from limited accumulation and poor penetration to the inner core of avascular or hypovascular tumors (such as prostate and pancreatic cancer),7-9 therefore nanomedicines small than 100 nm are more preferred for improved tumor penetration.10,11 Here we present our strategy to form cyclodextrin-based sub-30-nm nanocarriers, which allows easy drug encapsulation, and successful delivery of therapeutics to human tumor xenografts with significantly reduced tumor growth rates and improved survival rates. Citation Format: Xiaowei Ma, Ping Zhang, Chao Cui, Chang-Chun Ling, Lina Cui. Sub-30-nm capsules for drug delivery [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 280.
Abstract 1448: Combination therapy of anti-sense oligonucleotide targeting TGF-beta2 (TASO) and IL-2 (Proleukin) has anti-cancer effect in solid cancer
Authors: Jun-Eui Park, Jihye Koo, Hong-Kyu Lee, Tae Hun Kim
Journal: Cancer Research (2021)

Abstract Background: TGF-Β (transforming growth factor-beta) is an essential cytokine for tumor proliferation and metastasis. The expression of TGF-Β correlates with malignancy of various cancers and involves immunosuppression and angiogenesis of a tumor. IL-2 is a major cytokine to proliferate T cells and NK cells which are major players of cancer immunity. However, the toxicity of high dose IL-2 limits its use in cancer therapy. Combination treatment of TGF-Β inhibitor and IL-2 would have an anti-tumor effect by immune cells through diminishing immunosuppression by TGF-Β and enforcement of immune cells by IL-2. Trabedersen is an anti-sense oligonucleotide targeting human TGF-Β mRNA. It is shown that Trabedersen is well tolerable in cancer patients and effective reagent to treat pancreatic cancer, melanoma, and glioblastoma. Proleukin is the only approved IL-2 reagent to treat Renal cell carcinoma and Melanoma. Methods: Trabedersen and Proleukin activated human PBMC (Peripheral Blood Mononuclear Cell) are treated to several solid cancer cell lines, such as Breast cancer, Pancreatic cancer, Melanoma, Lung cancer, and Colon cancer to see the cytotoxicity effect of combination therapy of Trabedersen and Proleukin. NSG mouse (NOD Scid Gamma mouse, NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ) which are humanized by human PBMC engraftment and the tumor growth of Melanoma and TNBC (Triple Negative Breast Cancer cell) cell line are monitored. Results: The combination treatment of Trabedersen and low dose Proleukin decreased cancer cell viability in vitro experiment in solid cancer cell lines. Melanoma and TNBC tumor growth was delayed in humanized NSG mouse model by Trabedersen and low dose IL-2 combination therapy and tumor growth delay was statistically significant to Trabedersen alone or IL-2 alone group. Tumor infiltrating lymphocyte population was increased in Trabedersen treated group and FoxP3+ regulatory T cell population in blood and tumor microenvironment was decreased by treatment of Trabedersen. Conclusion: TGF-Β inhibitor (Trabedersen) and low dose IL-2 (Proleukin) combination treatment is expected to be an effective regimen in solid cancer treatment than individual treatment by alteration of tumor environment. Modulation of the dose of Proleukin expects to help reduce the toxicity of IL-2 and increase the anti-cancer effect by combination with Trabedersen. Citation Format: Jun-Eui Park, Jihye Koo, Hong-Kyu Lee, Tae Hun Kim. Combination therapy of anti-sense oligonucleotide targeting TGF-beta2 (TASO) and IL-2 (Proleukin) has anti-cancer effect in solid cancer [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 1448.
Mask related acne is a problem for healthcare workers and those with pigmented skins
Authors: Portia Goldsmith, Jing Gao, Shefali Rajpopat, Rebeca Goiriz
Journal: BMJ (2021)

Mask related acne and other facial dermatoses highlighted by Rudd and Walsh1 are big problems for healthcare workers (HCWs).

During the second peak of the pandemic, our trust had 12 975 HCWs employed in covid-19 work. We found HCWs were not well informed about how to manage skin problems induced by their personal protective equipment (PPE). To tackle this, we uploaded …
Abstract 2460: Oncogenic regulation of lipogenesis in docetaxel resistant prostate cancer cells
Authors: Shannalee R. Martinez, Adrián Pérez Aybar, Carlos J. Díaz Osterman
Journal: Cancer Research (2021)

Abstract Prostate cancer is the second leading cause of cancer related deaths in men in the United States. Docetaxel is the standard chemotherapeutic agent available for patients with advanced prostate cancer, in both hormone sensitive and castration resistant settings. However, the development of resistance to docetaxel curtails the efficacy of the drug in prostate cancer patients. Aberrant lipid metabolism has been linked to poor outcomes and therapy resistance in prostate cancer, particularly through overexpression and activation of lipogenic enzymes including ATP citrate lyase, acetyl coA carboxylase, fatty acid synthase, and stearoyl coA desaturase. Together, these enzymes drive fatty acid biogenesis, which has been linked to docetaxel resistance. The purpose of this study is to delineate the molecular mechanisms underlying the lipogenic reprogramming of docetaxel resistant prostate cancer cells, as these represent targets for reversal of this drug resistance. Docetaxel resistant sublines of LNCaP, 22rv1, PC3 and DU145 cell lines were established through chronic continuous exposure to incrementally increasing concentrations of docetaxel, followed by authentication by single tandem repeat (STR) analysis and validation of resistance using MTT viability assays and immunoblot detection of multidrug resistance protein 1 (MDR1/p glycoprotein/ABCB1). Enhanced intracellular accumulation of lipids using BODIPY 493/593 staining and flow cytometric detection was used to confirm the lipogenic phenotype of docetaxel-resistant cells. Oncogenic cMYC expression was also detected by immunoblotting, and its role in regulating lipogenic enzyme expression was evaluated by siRNA interference in docetaxel resistant prostate cancer sublines. cMYC knockdown suppressed the expression of lipogenic enzymes including acetyl coA carboxylase, fatty acid synthase, and stearoyl CoA desaturase in docetaxel-resistant prostate cancer cells. Furthermore, pharmacological inhibition of cMYC production (JQ1) or activity (10058-F4) effectively resensitized resistant cells to docetaxel, as did targeting of key lipogenic enzymes. These data indicate that a cMYC associated lipogenic program is associated with docetaxel resistance in prostate cancer and may represent targets for interventions to enhance docetaxel response in patients with advanced prostate cancer. Citation Format: Shannalee R. Martinez, Adrián Pérez Aybar, Carlos J. Díaz Osterman. Oncogenic regulation of lipogenesis in docetaxel resistant prostate cancer 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 2460.
Вплив функціональних порушень біліарного тракту на стан печінки в підлітків
Authors: A.V. Yeshchenko
Journal: GASTROENTEROLOGY (2013)

У статті показана провідна роль гіпокінетичної дисфункції біліарного тракту, порушення внутрішньопечінкового кровотоку по судинах дрібного й середнього діаметра й інтенсифікації вільнорадикального окислення ліпідів у формуванні початкових порушень функції печінки в підлітків.