tbuckley/cabot-search huggingface dataset:
Abstract CT160: Clinical application of a natural polypeptide, poly-γ-glutamic acid, which has immunotherapeutic efficacy
Authors: Jae-Kwan Lee, Kyung-Jin Min, Kwang Kim, Haryoung Poo, Moon-Hee Sung
Journal: Cancer Research (2016)

Abstract Poly-gamma-glutamic acid (γ-PGA) is known as viscous component of Korean chungkookjang and a natural polypeptide consisting of only glutamic acid with gamma-amide linkages. High molecular weight γ-PGA was isolated and mass-produced from Bacillus subtilisChungkookjang. Previously, accumulating evidences indicate that the γ-PGA inducesinnate immune response including natural killer (NK) cell activation and interferon secretion throughtoll-like receptor 4 (TLR4). To evaluate the immunotherapeutic effects, we’ve investigated the effect of γ-PGA on human NK cell activity and antiviral effect. First human study involving 99 healthy volunteers revealed thathigh-dosage γ-PGA group were significantly higher cytotoxic activities of NK cells than the low dosage and placebo groups at weeks 4 and 8 after the treatment. Furthermore, westudied the effect of γ-PGA on the treatment of vaginal intraepithelial neoplasia (VAIN). A retrospectiveobservational study on γ-PGA therapy for biopsy-proven VAIN suggest that γ-PGA may be helpful for the cytological regression and reduction of viral load in patients with high-risk HPV-positive VAIN. Since previous human studies showed the possibility of drug, we have accomplished a phase I dose escalation study to determine the safety, tolerance and pharmacokinetics of γ-PGA in healthy adult male subjects. The phase I study of oral γ-PGA was conducted in 20 healthy volunteers. There was no any significant difference in abnormal diagnoses or clinically relevant changes in laboratory parameters, vital signs, or other safety parameters. Currently, we have initiated a phase II trial to determine the efficacy and safety of γ-PGA compared with placebo in patients with cervical intraepithelial neoplasia grade 1 (CIN1). Total 200 patients with CIN1 will be administered with γ-PGA or placebo for 4 weeks followed by 8 weeks observation and compare the regression rate of CIN1.So far there was no serious adverse event (SAE) during phase II study. These results indicate that the oral administration of γ-PGAcan serve as treatment option that are safe and clinical efficacy via inducing NK cell activity and anti viral effect. Citation Format: Jae-Kwan Lee, Kyung-Jin Min, Kwang Kim, Haryoung Poo, Moon-Hee Sung. Clinical application of a natural polypeptide, poly-γ-glutamic acid, which has immunotherapeutic efficacy. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT160.
Abstract 2229: PD-L1 is expressed on CD11bhighCD14highHLA-DR+ myeloid cells in the tumor microenvironment of non-small cell lung cancer (NSCLC)
Authors: Chung-Hee Sonn, Yunji Oh, Tae Eun Kim, Jung Sun Ha, Hong Kwan Kim, Jong Ho Cho, Sumin Shin, Jhingook Kim
Journal: Cancer Research (2016)

Abstract Understanding the immune system of cancer patients is essential for the development of optimal treatment. We analyzed tumor cells and infiltrating immune cells in tumor tissues of NSCLC to determine the type of cells which expressed immune checkpoint molecules and/or their ligands, and compared them to clinicopathological characteristics. To obtain a single cell suspension from the tumor tissues of lung cancer patients, each fresh tumor sample was chopped and treated with collagenase and DNase. The dissociated tumor tissue cells (DTCs) were stained with fluorochrome-labeled mAbs and the distribution of immune cell components and expression of surface markers in DTCs were determined by FACSuite analysis. The yield of DTCs was 5.87±4.73×10⁁7/gram. PD-L1, which is a ligand for immune checkpoint molecule PD-1, is expressed on CD11bhigh myeloid cells in the blood, regardless of HLA-DR expression. On the other hand, PD-L1 is expressed on CD11highCD14highSSClow myeloid cells in the tumor site. All PD-L1 expressing cells were positive for HLA-DR, a ligand for a T cell receptor of CD4 T cells. Furthermore, these cells also expressed both CD86 and CD124. Interestingly, most tumor cells expressed very low levels of the PD-L1 molecule. And we found that CD11highCD14+HLA-DR- myeloid cells did not express PD-L1. The proportion of CD11highCD14+HLA-DR-PD-L1- myeloid cells was higher in advanced stage patients than early stage patients. In conclusion, PD-L1 is expressed on CD11bhighCD14highHLA-DR+SSClow myeloid cells, but not CD11bhighCD14+HLA-DR- myeloid cells. We propose that the PD-L1+ myeloid cells are likely to play an important role in tumor immunity. Further functional studies will be necessary to determine how the interaction between the cells will affect immunity. code noagegendersmokingstagecell typePD-L1+HLA-DR+CD14highCD11bhigh cells (%)PD-L1-HLA-DR-CD14+CD11bhi cells (%)L-03257maleyesIAmucinous adenocarcinoma39.81.2L-05281maleyesIAadenocarcinoma19.44.1L-04849maleyesIIIAsquamous cell carcinoma4.09.0L-02471maleyesIIIAadenocarcinoma11.20.4L-03665maleyesIVadenocarcinoma11.45.3L-04273maleyesIVadenocarcinoma21.65.5L-04674malenoIAadenocarcinoma6.11.6L-02167femalenoIBlarge cell, adenocarcinoma14.72.3L-01976femalenoIBadenocarcinoma15.816.7L-27145femalenoIVadenocarcinoma11.217.2L-27245femalenoIVadenocarcinoma9.924.8 Citation Format: Chung-Hee Sonn, Yunji Oh, Tae Eun Kim, Jung Sun Ha, Hong Kwan Kim, Jong Ho Cho, Sumin Shin, Jhingook Kim. PD-L1 is expressed on CD11bhighCD14highHLA-DR+ myeloid cells in the tumor microenvironment of non-small cell lung cancer (NSCLC). [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2229.
Heme Affects Sensitivity to Imatinib through Regulation of Nrf2 Activity in BCR/ABL-Positive Cell Lines.
Authors: Takuji Miyoshi, Tadashi Nagai, Makiko Nakamura, Ken Ohmine, Hiroyoshi Fujita, Shigeru Taketani, Norio Komatsu, Keiya Ozawa
Journal: Blood (2004)
Change in fracture risk and fracture pattern after bariatric surgery: nested case-control study
Authors: Catherine Rousseau, Sonia Jean, Philippe Gamache, Stéfane Lebel, Fabrice Mac-Way, Laurent Biertho, Laëtitia Michou, Claudia Gagnon
Journal: BMJ (2016)

To investigate whether bariatric surgery increases the risk of fracture. Retrospective nested case-control study. Patients who underwent bariatric surgery in the province of Quebec, Canada, between 2001 and 2014, selected using healthcare administrative databases. 12 676 patients who underwent bariatric surgery, age and sex matched with 38 028 obese and 126 760 non-obese controls. Incidence and sites of fracture in patients who had undergone bariatric surgery compared with obese and non-obese controls. Fracture risk was also compared before and after surgery (index date) within each group and by type of surgery from 2006 to 2014. Multivariate conditional Poisson regression models were adjusted for fracture history, number of comorbidities, sociomaterial deprivation, and area of residence. Before surgery, patients undergoing bariatric surgery (9169 (72.3%) women; mean age 42 (SD 11) years) were more likely to fracture (1326; 10.5%) than were obese (3065; 8.1%) or non-obese (8329; 6.6%) controls. A mean of 4.4 years after surgery, bariatric patients were more susceptible to fracture (514; 4.1%) than were obese (1013; 2.7%) and non-obese (3008; 2.4%) controls. Postoperative adjusted fracture risk was higher in the bariatric group than in the obese (relative risk 1.38, 95% confidence interval 1.23 to 1.55) and non-obese (1.44, 1.29 to 1.59) groups. Before surgery, the risk of distal lower limb fracture was higher, upper limb fracture risk was lower, and risk of clinical spine, hip, femur, or pelvic fractures was similar in the bariatric and obese groups compared with the non-obese group. After surgery, risk of distal lower limb fracture decreased (relative risk 0.66, 0.56 to 0.78), whereas risk of upper limb (1.64, 1.40 to 1.93), clinical spine (1.78, 1.08 to 2.93), pelvic, hip, or femur (2.52, 1.78 to 3.59) fractures increased. The increase in risk of fracture reached significance only for biliopancreatic diversion. Patients undergoing bariatric surgery were more likely to have fractures than were obese or non-obese controls, and this risk remained higher after surgery. Fracture risk was site specific, changing from a pattern associated with obesity to a pattern typical of osteoporosis after surgery. Only biliopancreatic diversion was clearly associated with fracture risk; however, results for Roux-en-Y gastric bypass and sleeve gastrectomy remain inconclusive. Fracture risk assessment and management should be part of bariatric care.
Current trends in HIV/ AIDS epidemiology in Poland, 1999 – 2004
Authors: M Rosinska
Journal: Eurosurveillance (2006)

The first HIV/ AIDS cases in Poland were diagnosed in the mid-1980, and the outbreak in injecting drug users was first observed in 1989. For many years the HIV epidemic in Poland was driven by injecting drug use. In this study we examine the trends in the HIV/ AIDS epidemic based on the surveillance data for 1999-2004. During this period, 3561 new HIV infections (annual rate of 15.4 per 1 000 000 inhabitants) were reported and 803 incident AIDS cases (incidence 3.5 per 1 000 000) were diagnosed. Both the annual number of newly detected HIV infections and the AIDS incidence showed a slight increasing trend. In particular, the vertically transmitted AIDS incidence increased from 0.46 in 1999 - 2000 to 0.91 per 1 000 000 children under 15 years in 2003 - 2004. Approximately 36% of AIDS patients aged 15 years or above had not been previously diagnosed with HIV. The annual number of the late presenters increased markedly between 1999 and 2004 and was higher amongst individuals infected through sexual transmission (51.0%) than those infected by injecting drug use (20.1%) . Injecting drug users made up 78.6% of new HIV infections with known transmission route, but for 47.9% of all cases the route of transmission was not reported. In order to generate more accurate data, HIV surveillance must be enhanced. Nevertheless, there is clear evidence for implementation of a comprehensive programme of prevention of vertical transmission and encouraging more extensive HIV testing especially in the groups at risk for sexual transmission. An effort is needed to enhance HIV surveillance and prevention in the framework of programmes for STI.
Difference between Enbrel and Benepali treatment groups in ‘hepatobiliary disorders’
Authors: Morton Scheinberg, Valderilio Azevedo
Journal: Annals of the Rheumatic Diseases (2016)

Difference between Enbrel and Benepali treatment groups in 'hepatobiliary disorders'We read with interest the study from Emery et al 1 reporting the phase III trial comparing the biosimilar SB4 with originator etanercept, as well as the summary for the public that appeared in the European Public Assessment Report (EPAR) 2 issued by European Medicines Agency on 28 January 2016.In our reading of the documents, we were struck by the discrepancy of reporting safety between these two documents.The discussion on clinical safety Benepali EPAR notes, one can read the following, 'There was a difference between the treatment groups in the hepatobiliary disorders System Organ Class Adverse Events (SOC AES): 17 treatment-emergent adverse events (TEAEs) in 11 patients reported in the Benepali (SB4) compared with no AEs in the EU Enbrel group (four events of cholelithiasis in four subjects, three events of liver disease disorder in three subjects, three events of chronic cholecystitis in two subjects, two events of bile duct stone in one subject and one event of biliary colic, cholangitis, cholecystitis and associated gall bladder perforation and elevated transaminases each reported in one subject.Could the authors comment on the decision to exclude this information from the primary manuscript and also help us understand the specific biliary risk factors in the Benepali arm that may have contributed to the hepatobiliary events.Given that the trials were very well balanced, this appears to be a rather significant difference between the two medicines.We feel that this additional information once provided may help to understand the nature of these differences and if the missing data on the composite outcomes could have an impact on whether patients receiving Benepali should be previously screened for gallbladder disease.
Abstract 3998: Sequencing the B-cell and T-cell repertoire
Authors: Fiona J. Stewart, Mehmet Karaca, Kris Adams, Chris Clouser, Bonny Patel, Sonia Timberlake, William Donahue, Lynne Apone, Salvatore Russello, Eileen T. Dimalanta, Theodore B. Davis, Francois Vigneault
Journal: Cancer Research (2016)

Abstract Immune sequencing allows for the study of complex immunological diseases by sequencing millions of V(D)J combinations from B-cell antibody and T-cell receptors. The popularity of this technique has increased due to recent throughput and read length improvements in next-generation sequencing technologies. However, structural and sequence complexities of antibody genes have made reliable targeting approaches challenging. We have developed and optimized a method for accurate sequencing of full-length immune gene repertoires of B-cells and T-cells. The method uses a unique barcoding scheme specifically designed to tag every mRNA molecule with a unique identifier (UID) so that all PCR copies of each mRNA fragment can be collapsed into a single consensus sequence. This makes the assay extremely accurate, by resolving PCR bias and sequencing errors as well as allowing quantitative digital molecule counting. Immune sequencing libraries were generated from total RNA extracted from Peripheral Blood Mononuclear Cells in duplicate from a single patient. The use of UIDs enabled absolute quantification of starting RNA molecules present in the original sample and therefore accurate ranking of the antibody clone abundance, by avoiding the bias incorporated by PCR or sequencing when total reads only were measured. Using the same sequencing method, tumor samples were analyzed for abundance of expanded clones via grouping clones by V gene, J gene and CDR3 similarity and ranking by mRNA abundance. Additionally, the use of isotype-specific primers (IgM, IgD, IgG, IgA and IgE) enabled measurement of the heavy chain isotype proportions within the samples. Further, alignment of full-length heavy chain antibody sequences generated using this method to germline genes from reference databases enabled quantitation of the mutation level of each antibody sequence, thereby providing information on the overall maturity and mutational profile of the sample repertoire. Citation Format: Fiona J. Stewart, Mehmet Karaca, Kris Adams, Chris Clouser, Bonny Patel, Sonia Timberlake, William Donahue, Lynne Apone, Salvatore Russello, Eileen T. Dimalanta, Theodore B. Davis, Francois Vigneault. Sequencing the B-cell and T-cell repertoire. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3998.
Response to Comment on Rosenstock and Ferrannini. Euglycemic Diabetic Ketoacidosis: A Predictable, Detectable, and Preventable Safety Concern With SGLT2 Inhibitors. Diabetes Care 2015;38:1638–1642
Authors: Julio Rosenstock, Ele Ferrannini
Journal: Diabetes Care (2016)

We were surprised that Dr. Cushard felt uneasy (1) with our commentary (2) stating that euglycemic diabetic ketoacidosis (euDKA) induced by sodium–glucose cotransporter 2 inhibitors (SGLT2i) was not just “predictable” but also “detectable” and “preventable.” However, in regard to the case he reports, it is clear that more efforts should have been spent to persuade the patient to start the much needed insulin to address the severe hyperglycemia and ketonuria instead of doing unnecessary testing such as serum insulin, C-peptide, and, for whatever clinical purpose, HOMA-B and insulin resistance calculation. Thus, as outlined in our commentary, this event could have been easily prevented. Clearly this patient with poorly controlled diabetes despite treatment with sitagliptin, metformin, and glipizide needed insulin instead of switching to dapagliflozin and stopping the sulfonylurea, as presumably the SGLT2i only counteracted the expected deterioration of glucose control with the discontinuation of glipizide.

Before SGLT2i treatment was initiated, Dr. Cushard’s patient …
Long Term Safety and Efficacy of Sustained Eculizumab Treatment In Patients with Paroxysmal Nocturnal Hemoglobinuria (PNH)
Authors: Robert A Brodsky, Carlos de Castro, Hubert Schrezenmeier, Antonio M. Risitano, Joerg Schubert, Jaroslaw P Maciejewski, Ulrich Duehrsen, Lucio Luzzatto, Petra Muus, Jeffrey Szer, Gérard Socié, Peter Hillmen
Journal: Blood (2010)
Dendritic Cells (DC) Generated from AML Blasts Express Leukemia Associated Antigens Eliciting Specific Cytotoxic T Cell Responses in the Autologous Host after DC Vaccination.
Authors: Li Li, Peter Reinhardt, Iwona Hus, Jacek Rolinski, Anna Dmoszynska, Markus Wiesneth, Hartmut Dohner, Michael Schmitt
Journal: Blood (2004)
Abstract 239: Alteration of drug sensitivity according to the induction and reversion of epithelial-to-mesenchymal transition (EMT) in human lung adenocarcinoma cell lines harboring an EGFR mutation
Authors: Ryota Kurimoto, Shunichiro Iwasawa, Takahiro Ebata, Tsukasa Ishiwata, Ikuo Sekine, Yuji Tada, Koichiro Tatsumi, Shuhei Koide, Atsushi Iwama, Yuichi Takiguchi
Journal: Cancer Research (2016)

Abstract Introduction: EMT phenotype is known to relate to drug resistance and immune tolerance of cancer. However, mechanism underling these phenomena, including the mechanism of the induction and reversion of EMT, are not fully understood. Methods: EGFR mutated human lung adenocarcinoma cell lines, HCC-827 and PC-9, were treated with TGF-ß and/or FGF-2 to induce EMT. EMT was reversed by treating the induced EMT cells with either of PP242 (mTOR inhibitor), metformin and DMSO. The phenotypic alterations according to the induction and reversion of EMT were accessed by a wound healing assay for mobility, flow cytometry for cell cycle, MTT and apoptosis assays for drug sensitivity to cisplatin and gefitinib, and RT-PCR and fluorescence IHC for PD-L1 expression. Results: The treatment with combination of TGF-ß/FGF-2 showed an efficient increase in expressions of mesenchymal markers and slug in both cell lines, and a decrease in E-cadherin expression in HCC827. In immunoblotting analyses, the Smad3 pathway in PC-9, and the Smad3, MEK/Erk and mTOR pathways in HCC-827 were involved in the induction of the EMT. The induced EMT was accompanied by enhanced cell motility and accumulation in the G0/G1 phases in both cell lines. The induced EMT also made the cells less sensitive to gefitinib in both cell lines, and to cisplatin in HCC-827. Increased PD-L1 expression was observed in both cell lines. Treatment of the induced EMT cells with PP242, metformin and DMSO reverted the altered expressions of epithelial and mesenchymal markers, cell motility and cell cycle. These agents reverted the EMT to different extents and through different pathways, depending on the cell lines. Reversion of the EMT using each of the 3 agents partly restored drug sensitivity, and suppressed PD-L1 expression. Conclusion: Inducing EMT by treatment with TGF-ß/FGF-2 is an effective way to acquire drug resistance and up-regulation of PD-L1. Reversion of the EMT, therefore, has a potential to overcome drug resistance and immune tolerance of cancer. Citation Format: Ryota Kurimoto, Shunichiro Iwasawa, Takahiro Ebata, Tsukasa Ishiwata, Ikuo Sekine, Yuji Tada, Koichiro Tatsumi, Shuhei Koide, Atsushi Iwama, Yuichi Takiguchi. Alteration of drug sensitivity according to the induction and reversion of epithelial-to-mesenchymal transition (EMT) in human lung adenocarcinoma cell lines harboring an EGFR mutation. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 239.
P126 Medical Thoracoscopy Experience in a District General Hospital: Abstract P126 Table 1
Authors: S Selvaraj, U Maqsood, M Chaudri, P Brammer
Journal: Thorax (2012)

<h3>Background</h3> In patients with pleural effusion, even after extensive diagnostic evaluation, the aetiology often remains unclear. The diagnostic yield from simple pleural fluid aspiration and blind pleural biopsy is very limited. Medical thoracoscopy can be performed under controlled sedation and enables direct visualisation of the pleural surfaces to obtain targeted sampling, to improve the diagnostic yield.<sup>1</sup> <h3>Aim</h3> To review local practise and experience of medical thoracoscopy. <h3>Methods</h3> Retrospective analysis of 112 cases over a period of four years was performed to look at the diagnostic yield. We compared simple pleural aspiration with thoracoscopy and examined the relationship between the computed tomography (CT) appearances and histology results. <h3>Results</h3> Of the 112 cases, 83 (74%) were male and 27 (26%) female. The age range was 32 to 90 years (mean – 69). No major adverse events were reported following the procedure. Two patients had the procedure performed twice due to recurrence. One sample was lost. The results for the remaining 111 patients are presented in the table. Of the 69 patients who were diagnosed with malignancy, pleural fluid aspiration was positive in only 29 (43%) cases. CT evidence of pleural thickening was noted in only 28 (41%) of these cases, all of which turned to be malignant. <h3>Conclusions</h3> Our study reiterates the fact that medical thoracoscopy has a better diagnostic yield than simple pleural aspiration and is a safe procedure that can be performed safely by chest physicians in a DGH setting. In our case series the presence of pleural thickening on CT was a strong predictor of malignancy. However the majority of malignant cases had no evidence of pleural thickening. <h3>Reference.</h3> BTS pleural disease guideline - 2010.
Inhibition of Growth of Neoplastic Mast Cells by CD44 mAb A3D8 Is Associated with G1 Cell Cycle Arrest and Apoptosis.
Authors: Alexandra Boehm, Stefan Florian, Karoline Gleixner, Karoline Sonneck, Karl J. Aichberger, Sophia Derdak, Winfried F. Pickl, Peter Valent, Wolfgang R. Sperr
Journal: Blood (2005)