tbuckley/cabot-search huggingface dataset:
Abstract MP079: Coronary Artery Calcium Incidence and Progression Among South Asians: Results From the MASALA Study
Authors: Alka M Kanaya, Namratha Kandula, David Herrington, Kiang Liu, Matthew Budoff
Journal: Circulation (2017)

Background: South Asians have a high burden of cardiovascular disease. We have reported that South Asians have similarly high prevalence of coronary artery calcium (CAC) compared to non-Hispanic Whites, and higher CAC than other U.S. ethnic minority groups. No studies have determined the incidence or progression of CAC among South Asians. Methods: We used data from a community-based cohort of South Asians (MASALA) and calculated change in CAC Agatston score between Exam 1 (2010-2013) and Exam 2 (2015-2016) among 379 South Asians. We calculated the average annual incident CAC for those with no CAC at Exam 1, and CAC progression among those with CAC at Exam 1. We compared these findings to the previously reported CAC incidence and progression in the Multi-Ethnic Study of Atherosclerosis (MESA). We also determined factors associated with a ≥100 change in CAC score. Results: We used data from 240 men and 139 women with repeat CAC measured after 4.5±0.7 years of follow-up. Among those with no detectable CAC at baseline, 6.8% developed incident CAC annually (9.2% of men and 4.4% of women), which was similar to MESA race/ethnic groups. Among those with known CAC at baseline, the median annual CAC progression was 23 (interquartile range, 8-56). The table shows the distribution of annual CAC progression. South Asians overall, but particularly South Asian men, had significantly higher annual CAC progression compared to the reported average in MESA (overall median 18, 4-53). Established risk factors (age, male sex, diabetes and hypertension), pericardial fat volume and visceral fat area were associated with greater CAC progression. Conclusions: These preliminary results suggest that South Asian men have significantly greater CAC progression compared to other race/ethnic groups. Longer follow-up of MASALA will determine whether CAC score or CAC progression are important predictors of cardiovascular disease events.
HCT related toxicities and mortality in frail recipients.
Authors: Merve Pamukcuoglu, Smita Bhatia, Daniel Jordan Weisdorf, Todd E. DeFor, Celalettin Ustun, Manju Nayar, Shernan Holtan, Najla H. El Jurdi, Bharat Thyagarajan, Claudio Brunstein, Veronika Bachanova, Erica D. Warlick, Mukta Arora
Journal: Journal of Clinical Oncology (2019)

e18534 Background: Frailty is a state characterized by diminished physiological reserve and increased vulnerability to stress, and adversely affects outcomes in older patients with cancer. Geriatric assessments are not routinely used to screen older HCT (hematopoietic cell transplant) recipients. There is limited knowledge of the impact of pre-HCT frailty on severe/ life-threatening (CTCAE, version 5.0) grade 3-4 non-hematologic toxicities within 1y after HCT. We aimed to determine the relationship between pre-HCT frailty and grade 3-4 non-hematologic toxicities and mortality in HCT recipients, and also examined whether age at HCT moderated that association. Methods: In a prospective longitudinal study of 117 patients undergoing HCT at age ≥ 40y, we performed pre-HCT geriatric assessments. Frailty was assessed using Fried’s criteria. Post-HCT toxicities were abstracted through chart reviews Results: Median age at HCT was 60y (40-73). Pre-HCT frailty could be evaluated in 98 (84%) patients [(51 autologous, 47 allogeneic (allo)]. Pre-HCT comorbidity index (CI) was high in 27%, intermediate in 40% and low in 33%. The prevalence of pre-HCT frailty was 21%. Overall, frail recipients (vs. non-frail) had a higher cumulative incidence of any grade 3-4 toxicity [86% (95% CI: 62-100%) vs. 70% (57-83%), p = 0.03]; and the following organ specific grade 3-4 toxicities: non-neutropenic infections [(38% (17-59%) vs. 13% (6-20%), p &lt; 0.01)]; nervous system disorders [(19% (3-35%) vs. 4% (0-8%), p = 0.02)]; and pneumonia [(38% (17-59%) vs. 10% (4-17%), p &lt; 0.01]. Frail recipients also had a higher overall mortality [52%, (30-75%) vs. 19%, (11-28%) (p &lt; 0.01)]. In Cox regression analysis controlling for age, donor type, disease risk, conditioning and HCT-CI, frail recipients were 1.9 fold more likely to suffer any grade 3-4 toxicities (p = 0.03), 4-fold more likely to suffer non-neutropenic infections and pneumonia, both p = 0.01; and 8.6-fold more likely to suffer nervous system disorders, p = 0.01. Frail recipients who underwent an allo-HCT were at 2.7 fold higher risk of death vs. non-frail allo- HCT recipients, p = 0.06. Conclusions: The higher toxicity and mortality in frail recipients needs attention. Studies focusing on pre-HCT interventions to reduce frailty are needed.
GP who altered a medical report in accident insurance claim is suspended for 12 months
Authors: Clare Dyer
Journal: BMJ (2019)

A GP who altered a medical report at a solicitor’s request in an accident insurance claim has been suspended from the UK medical register for 12 months.

Asef Zafar initially wrote that a taxi driver’s injuries from a car accident had caused mild pain and stiffness that resolved after a week. But after the patient complained to his solicitor, who then contacted Zafar, a new report was produced saying that his injuries would take six to eight months to resolve.

The deception was uncovered in August 2013 when both medical reports, bearing the same date, were inadvertently left in a bundle of legal papers submitted to the court.

Liverpool Victoria, the insurers of the other driver, took contempt of court proceedings against the doctor, which …
A Chitosan–Carbon Nanotube‐Modified Microelectrode for In Situ Detection of Blood Levels of the Antipsychotic Clozapine in a Finger‐Pricked Sample Volume
Authors: Rajendra P. Shukla, Hadar Ben‐Yoav
Journal: Advanced Healthcare Materials (2019)

Abstract The antipsychotic clozapine is the most effective medication available for schizophrenia and it is the only antipsychotic with a known efficacious clinical range. However, it is dramatically underutilized due to the inability to test clozapine blood levels in finger‐pricked patients' samples. This prevents obtaining immediate blood levels information, resulting in suboptimal treatment. The development of an electrochemical microsensor is presented, which enables, for the first time, clozapine detection in microliters volume whole blood. The sensor is based on a microelectrode modified with micrometer‐thick biopolymer chitosan encapsulating carbon nanotubes. The developed sensor detects clozapine oxidation current, in the presence of other electroactive species in the blood, which generate overlapping electrochemical signals. Clozapine detection, characterized in whole blood from healthy volunteers, displays a sensitivity of 32 ± 3.0 µA cm −2 µmol −1 L and a limit‐of‐detection of 0.5 ± 0.03 µmol L −1 . Finally, the developed sensor displays a reproducible electrochemical signal (0.6% relative standard deviation) and high storage stability (9.8% relative standard deviation after 8 days) in serum samples and high repeatability (9% relative standard deviation for the 5th repetition) in whole blood samples. By enabling the rapid and minimally invasive clozapine detection at the point‐of‐care, an optimal schizophrenia treatment is provided.
Abstract 4745: Reversal by inhibiting XBP1 activation of glucose deprivation-induced tolerance to multiple anticancer therapies
Authors: Mini Jeong, Serin Jo, Serkin Park, Jeongwon Sohn, Yun Gyu Park
Journal: Cancer Research (2019)

Abstract Tumor microenvironment is harsh condition including low pH, hypoxia and nutrient deprivation. Cancer cells can switch their phenotypes and characteristics dependent on the microenvironment. Most previous researches have focused mainly on the effect of hypoxia on cancer cells plasticity and resistance to anticancer therapies. Despite the accumulation of emerging evidences, the effect of nutrient deficiency to multiple anticancer therapies is still unclear.In this study, human lung adenocarcinoma cells (A549), triple-negative breast cancer (MDA-MB-231), hepatocellular carcinoma cells (HepG2), pancreas adenocarcinoma cells (AsPC-1) were cultured in the medium containing low concentrations of glucose. Low sensitivity to cisplatin or taxol was observed in the cancer cells maintained for 28 weeks or so under the glucose-deprived condition. In addition, the multidrug tolerant cells were also insensitive to cytotoxic T cell (CTL)-based immunotherapy and had increased migration ability compared with control group under normal glucose condition. Reversion to normal glucose condition only for short term period (at least 4 days) made the multidrug tolerant cells susceptible to cisplatin-induced apoptotic cell death. In the unfolded protein response, BiP-XBP1 signaling was increased but PERK signaling was decreased in response to long-term glucose deprivation. Sensitivity to cisplatin treatment and CTL-based immunotherapy was restored by inhibiting XBP1 splicing in glucose deprivation-induced multidrug tolerant cells in various types of cancer.This study demonstrated that glucose deprivation-induced tolerance to multiple anti-cancer therapies is transient and reversible, and requires activation of IRE1-XBP1 pathway.This research was supported by the National Research Foundation of Korea (2018R1D1A1B07045297, 2016R1D1A1A02936945 and 2017R1D1A1B03036008). Citation Format: Mini Jeong, Serin Jo, Serkin Park, Jeongwon Sohn, Yun Gyu Park. Reversal by inhibiting XBP1 activation of glucose deprivation-induced tolerance to multiple anticancer therapies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4745.
Abstract 896: Knocking out the gene (SNCA) that codes for the Parkinson’s disease-related protein alpha-synuclein in SK-Mel-28 melanoma cells significantly retards tumor growth in SCID mice
Authors: Sahar Shekoohi, Santhanasabapathy Rajasekaran, Shu Yang, Sureshbabu Nagarajan, Dhaval Patel, Xiuping Yu, Stephan N. Witt
Journal: Cancer Research (2019)

Abstract The Parkinson’s disease-associated protein alpha-synuclein (α-syn) is often highly expressed in melanoma. α-Syn appears to exert a pro-survival function in melanoma cells, possibly by maintaining autophagy homeostasis. The long-term goal of our work is to determine the mechanism by which α-syn confers survival in melanoma cells. Herein, we used CRISPR (clustered regularly interspaced short palindromic repeats) to disrupt SNCA, the gene that codes for α-syn, in the melanoma cell line SK-Mel-28. Western blotting and real-time-qPCR verified that we generated four α-syn knockout (KO) clones. Three clones showed no expression of α-syn, whereas one had about 50% less α-syn than the control cells. DNA sequencing is consistent with three of the clones having both alleles of SNCA knocked out, whereas one clone has only one allele knocked out. α-Syn KO clones were tested in a variety of assays to ascertain the function of α-syn. First, the percentage of cells with exofacial phosphatidylserine (PS) was determined by annexin V-FITC/PI staining in conjunction with fluorescence-activated cell sorting. On average, there was a statistically significant 50% increase in exofacial PS (annexin V+/PI-) in three of the four α-syn KO clones compared to control cells. Exofacial PS was increased in the α-syn KO clones without a concomitant increase in apoptotic cells (annexin V+/PI+). Second, the clones were tested for growth in vivo using SCID mice. All four clones showed a ~65% reduction in the rate of tumor growth, followed over 12 weeks. Third, immunohistochemical staining of excised tumors from the SCID mice showed that the proliferation marker Ki-67 was significantly (p&amp;lt; 0.0001) lower in the tumors generated from the KO clones compared to tumors from control cells. In conclusion, given that α-syn avidly binds to PS, one possibility is that α-syn is like molecular Velcro that binds to PS molecules embedded in the inner leaflet, and this binding helps ATP-driven flippases keep PS in the inner leaflet. Loss α-syn then increases exofacial PS, which is a marker of senescence. Our working model is that α-syn is an anti-senescence protein, and that the α-syn KO clones grow slower than control cells in vivo because the clones have entered a senescent state. Citation Format: Sahar Shekoohi, Santhanasabapathy Rajasekaran, Shu Yang, Sureshbabu Nagarajan, Dhaval Patel, Xiuping Yu, Stephan N. Witt. Knocking out the gene (SNCA) that codes for the Parkinson’s disease-related protein alpha-synuclein in SK-Mel-28 melanoma cells significantly retards tumor growth in SCID mice [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 896.
Abstract 1240: Identification of molecular targets of Tris DBA [Tris(dibenzylideneacetone)dipalladium(0)] for cancer therapy
Authors: Loukik Arora, Chris Soon Heng Tan, Radoslaw M. Sobota, Gautam Sethi
Journal: Cancer Research (2019)

Abstract Cancer is complex disease involving complex genetic and epigenetic heterogeneity making it the second leading cause of death globally after heart disease. While conventional treatments like surgery, radiotherapy, chemotherapy are principal strategies, the focus is shifting to therapies that can target multiple pathways to treat cancers. In the present report, we hypothesized that Tris DBA, an organometallic compound, can inhibit proliferation, tumor growth, and induce apoptosis in multiple myeloma (MM) and hepatocellular carcinoma (HCC) cells, thereby potentially exhibiting significant anticancer effects. Our preliminary results clearly indicated that Tris DBA could substantially inhibit both constitutive as well as IL-6 inducible STAT3 activation and abrogate proliferation/survival in MM and HCC cells. A phospho-proteomic profiling revealed several key phosphorylation changes induced by Tris DBA treatment which further indicate broad anticancer potential of the compound. Additionally, the agent exhibited potent antitumor actvitiy in vivo, with little adverse effects. The ongoing work is aimed at investigating the possible binding target(s) of Tris DBA and further characterize the molecular mechanism(s) underlying STAT3 inhibitory effects of the drug. Citation Format: Loukik Arora, Chris Soon Heng Tan, Radoslaw M. Sobota, Gautam Sethi. Identification of molecular targets of Tris DBA [Tris(dibenzylideneacetone)dipalladium(0)] for cancer therapy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1240.
Abstract LB-115: Preclinical assessment of retinoid X-receptor agonist, UAB110, for potential treatment of cutaneous T-cell lymphoma
Authors: Chu-Fang Chou, Jason Esla, Venkatram Atigadda, Donald Muccio, Clinton Grubbs, Elmets Craig, Pi-Ling Chang
Journal: Cancer Research (2019)

Abstract Cutaneous T-cell lymphomas (CTCLs) are a group of non-Hodgkin diseases characterized by localization of neoplastic T-cells in the skin. The most common forms of CTCLs are mycosis fungoides (MF) and Sézary syndrome (SS). Bexarotene (Targretin®) is currently the only FDA approved retinoid X receptor (RXR) -selective agonist (rexinoid) for the treatment of CTCLs. Despite its low toxicity compared to retinoids and other chemotherapeutic agents, it induces hypothyroidism and markedly elevates serum triglycerides (TGs). Thus, improved rexinoids for the treatment of this indolent disease is necessary. A potential candidate is the novel rexinoid, UAB110, which does not elevate TGs in animal studies and effectively prevents mammary cancer development. Compared to bexarotene, it has higher binding affinity for RXRα receptor and transcriptional activation activity. The purpose of this study is to assess preclinical efficacy, mechanism of action of UAB110, and compare its action with bexarotene and the rexinoid 9-cisUAB30 (UAB30) using human-derived CTCL cell lines, MyLa and HuT78, which are representative of MF and SS, respectively. Cell proliferation analysis and cell-cycle related markers were determined by hemocytometer and Western blot analysis, respectively. UAB110 is as effective as UAB30 and bexarotene in suppressing cell proliferation. Furthermore, it significantly (p &amp;lt; 0.05 relative to DMSO control) suppresses the protein expression of SKP2 (S-phase kinase-associated protein 2, a F-box protein that targets p27kip1 for degradation by 26S proteasome) and PSMA7 (proteasome subunit alpha type 7, a component of the 20S proteolytic complex in 26S proteasome). The decrease in SKP2 resulted in a concomitant up-regulation of p27kip1 protein, the major cell cycle inhibitor. The downregulating of PSMA7 impaired the 20S proteasome activity in both cell lines. These findings indicate that the novel rexinoid is effective in inhibiting cell proliferation of CTCL cells, in part, by suppressing SKP2 expression and the 20S proteasome activity resulting in increasing p27kip1 protein. In sum, UAB110 and also UAB30 with minimal effect in elevating serum TGs are both possible alternatives to bexarotene for the treatment of CTCLs. Citation Format: Chu-Fang Chou, Jason Esla, Venkatram Atigadda, Donald Muccio, Clinton Grubbs, Elmets Craig, Pi-Ling Chang. Preclinical assessment of retinoid X-receptor agonist, UAB110, for potential treatment of cutaneous T-cell lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr LB-115.
Weighting the impact of virulence on the outcome of Pseudomonas aeruginosa bloodstream infections
Authors: I. Sánchez-Diener, L. Zamorano, C. Peña, A. Ocampo-Sosa, G. Cabot, S. Gómez-Zorrilla, B. Almirante, M. Aguilar, A. Granados, E. Calbo, J. Rodriguez-Baño, F. Rodríguez-López, F. Tubau, L. Martínez-Martínez, A. Navas, A. Oliver
Journal: Clinical Microbiology and Infection (2019)
Abstract 3973: Nivolumab-based ELISA revealed increased serum PD-1 levels in advanced RCC patients
Authors: Kosuke Mizutani, Kengo Horie, Taku Kato, Keita Nakane, Kyojiro Kawakami, Yasunori Fujita, Masafumi Ito
Journal: Cancer Research (2019)

Abstract Introduction: Antibody therapy has been successfully used for several caners, but the efficacy is still limited. To select patients that respond well to the therapy, development of companion diagnostics is essential. Although PD-L1 expression determined by immunohistochemistry has been shown to be a marker to select patients with non-small-cell lung cancer who will benefit from antibody therapy, its potential for Nivolumab treatment in renal cell carcinoma (RCC) patients is unclear. Detection of the soluble form of PD-1 in serum has been reported, but there are few studies demonstrating its clinical role in RCC. Antibody-based assays may rely on characteristics and quality of antibody used. We hypothesized that the use of Nivolumab as a capture antibody in ELISA would give more clinically relevant results to evaluate the serum PD-1 levels in RCC patients. Materials and Methods: After approval of the study by the Medical Review Board of Gifu University, a total of 71 participants were recruited (22; healthy volunteers, 29; localized RCC and 20; RCC patients with metastasis or recurrence). Serum PD-1 levels were determined using PD-1 Human ELISA Kit (Thermo Fisher Scientific Inc., MA, USA). For Nivolumab-based ELISA, a capture antibody included in the kit was changed to Nivolumab. Nivolumab was coated to 96-well microplates using a commercially available kit. Results: Medians of the serum PD-1 levels measured by conventional ELISA were 31.8, 29.8 and 34.3 pg/ml in healthy volunteers, localized RCC patients and those with metastasis or recurrence, respectively, which showed no statistically significant difference. When the same set of patients were analyzed by Nivolumab-based ELISA, medians were 24.6, 23.7 and 46.4 pg/ml and the serum PD-1 levels were significantly elevated in patients with metastasis or recurrence (P = 0.013) compared to controls and localized patients. Of the 29 localized patients, 3 patients with relatively higher serum PD-1 levels at initial diagnosis relapsed later. Among 6 patients with metastasis who were treated with Nivolumab, well responders showed relatively lower serum PD-1 levels before treatment. Conclusion: The serum PD-1 levels determined using Nivolumab were increased in advanced RCC patients. Our results suggest that the detection of target molecules using a therapeutic antibody may yield more clinically relevant information, thus providing a novel approach to develop companion diagnostics. Citation Format: Kosuke Mizutani, Kengo Horie, Taku Kato, Keita Nakane, Kyojiro Kawakami, Yasunori Fujita, Masafumi Ito. Nivolumab-based ELISA revealed increased serum PD-1 levels in advanced RCC patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3973.
Abstract 16980: A High Throughput Assay for PCSK9 Proteolysis Reveals its Substrate Specificity
Authors: John S Chorba, Adri Galvan, Kevan M Shokat
Journal: Circulation (2017)

PCSK9 binds and directs the LDL receptor (LDL-R) for lysosomal degradation, reducing surface LDL-R levels and elevating serum LDL cholesterol (LDL-C). Targeting PCSK9 has thus proven an attractive ...
Abstract 615: Roles of <i>XRCC1</i> genetic polymorphism in head and neck cancer patients receiving radiation therapy in Taiwan
Authors: Shiang-Fu Huang, Huei-Tzu Chien, Chun-Ta Liao, Hung-Ming Wang, Yuan-Hung Wang
Journal: Cancer Research (2019)

Abstract In Taiwan, oral cancer (including sub-sites in the oral cavity, oropharynx and hypopharynx) is the fourth most common cancer in men. The incidence of oral cancer still increased in the past decade. Oxidative stress generated from cigarette smoking, AQ chewing and alcohol drinking was shown to contribute to oral cancer development. The oxidative stress associated DNA lesions are repaired via the DNA base excision repair (BER) pathway. In constrast, radiation therapy was an important treatment modality either as primary or adjuvant in these patients. Ionizing radiation induced DNA damage was also repaired by BER related mechanisms. To investigate the role of BER genes XRCC1 in patients receiving radiation therapy in Taiwan, a comprehensive study on evaluation of polymorphisms of XRCC1 genes was carried out in 753 oral cancer male cases received radiation therapy as primary or adjuvant treatment. Patients with XRCC1 194Arg, XRCC1 280Arg, and XRCC1399Gln homozygous genotypes had worse disease-free survival (p = 0.015, p = 0.587 and p = 0.013, respectively). A linkage disequilibrium exists between XRCC1 194Arg and XRCC1 399Gln genotyping. We further investigated the influence of XRCC1 194Arg and XRCC1 399Gln haplotype in the radiation effects in oral cancer patients. XRCC1 194 Arg/Arg homozygous and its combination with XRCC1 399 Arg/Gln genotyping were selected. We found that the XRCC1 194Arg/Arg and XRCC1 399Gln/Gln haplotype had the worse survival (p = 0.022, ). Multivariate Cox regression adjusting tumor stage, lymph node metastasis and tumor differentiation confirmed that XRCC1 194Arg and XRCC1 399Gln haplotype was an independent prognostic factor for oral cancer receiving radiation therapy. These indicated that XRCC1 194Arg and XRCC1 399Gln genotypes had adverse influence in oral cancer patients receiving radiation therapy. XRCC1 194Arg and XRCC1 399Gln haplotype predicts poor prognosis in these patients. Citation Format: Shiang-Fu Huang, Huei-Tzu Chien, Chun-Ta Liao, Hung-Ming Wang, Yuan-Hung Wang. Roles of XRCC1 genetic polymorphism in head and neck cancer patients receiving radiation therapy in Taiwan [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 615.