tbuckley/cabot-search huggingface dataset:
Abstract 1699: Protumoral role of trans fatty acid in colorectal cancer
Authors: Hitoshi Ohmori, Toshio Kuwai, Yasuhiko Kitadai, Kiyomu Fujii, Rina Fujiwara, Yukiko Nishiguchi, Tomonori Sasahira, Hiroki Kuniyasu
Journal: Cancer Research (2016)

Abstract Trans fatty acids (TFAs) is a recent focus of health problems. TFA is a definitive risk factor for cardiovascular diseases and the death. TFA is also possible risk factor for Alzheimer's disease, obesity, diabetes, fatty liver, and ovulation infertility. Relation of TFA with carcinogenic risk is controversy; however, TFA is reported to increase the risk of breast cancer and prostate cancer. Elaidic acid (EA), a trans form of oleic acid, enhances cancer cell growth, invasion, and anti-apoptotic survival. By animal models, EA promotes tumor growth and metastasis to the lung, liver, and peritoneum. EA induces stemness in cancer cells through transactivation of EFGR via SRC from GPR40/120 as receptors in EA-integrated cholesterol raft. Activated EGFR relays the signals to activate canonical and non-canonical wnt pathway and to inactivate notch1 pathways. EA also increases miR-494, which inhibits cell differentiation through decrease of target genes. Continuous EA feeding with dosage alteration increased cancer cell stemness. EA diminishes the efficiency of 5-fluorouracil by increase of residual cancer stem cells. These findings suggest that TFA is a relevant cancer promoting factor. Decision of removal of TFA from foods by FDA might provide an impact to cancer clinics. Citation Format: Hitoshi Ohmori, Toshio Kuwai, Yasuhiko Kitadai, Kiyomu Fujii, Rina Fujiwara, Yukiko Nishiguchi, Tomonori Sasahira, Hiroki Kuniyasu. Protumoral role of trans fatty acid in colorectal cancer. [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 1699.
Abstract 657: N-Myc and STAT Interactor knock out in the mammary epithelium prompts hyper-proliferation
Authors: Hawley C. Pruitt, Brandon J. Metge, Sarah K. Bailey, Lalita A. Shevde, Rajeev S. Samant
Journal: Cancer Research (2016)

Abstract N-Myc and STAT Interactor (NMI) is an evolutionarily conserved protein that is widely expressed in fetal and adult tissues. Early studies implicated its role in regulating the activities of transcription factors (such as MYC, STATs, BRCA1, TIP60 etc.) critical to tumor progression and metastasis. However, the functional relevance of these regulatory activities of NMI remains unknown. Recent findings from our lab have revealed that NMI protein expression is decreased by 70% in primary tumor specimens from patients with metastatic breast cancer. Most recently, we have found that lack of NMI expression in breast cancer cells confers resistance to chemotherapy by blocking autophagy-induced cell death. Thus the status of NMI expression in breast cancer patients may be an important clinical consideration. Additionally, our functional studies have demonstrated that loss of NMI expression allows manifestation of TGFβ and Wnt driven EMT that results in increased invasion and metastatic dissemination. Overall, we have noticed a profound impact of NMI on multiple developmental signaling pathways that are essential for mammary development as well as tumor progression. To further elucidate the biological role of NMI, we have created a genetically engineered mammary specific Nmi knock out model. We observed that in normal murine mammary tissue Nmi is expressed in the mammary epithelium during all stages of mammary development. However, it's expression is strikingly induced at the onset of pregnancy, implicating an important role of NMI in mammary ductal development and/or lactation. Remarkably, the Nmi knock out mice exhibit distinctly increased number of alveolar structures (30% more than in control mice) during lactation. Moreover, these Nmi-/- mammary glands also show 20% more proliferating mammary epithelial cells (MECs) compared to respective littermate controls. In addition, 3D-alveologenesis of Nmi knock out MECs is highly responsive to induction by growth factors such as TGFα and FGFs when compared to MECs from littermate controls. Hyper-proliferative phenotype has been implicated as one of the key factors for breast cancer initiation as well as progression. Overall, our work describes a direct evidence for the role of NMI as a key regulator of mammary epithelial cell proliferation. Citation Format: Hawley C. Pruitt, Brandon J. Metge, Sarah K. Bailey, Lalita A. Shevde, Rajeev S. Samant. N-Myc and STAT Interactor knock out in the mammary epithelium prompts hyper-proliferation. [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 657.
Air pollution affects lung cancer survival
Authors: Jaime E Hart
Journal: Thorax (2016)

Lung cancer is one of the most commonly occurring cancers in the USA. The American Cancer Society estimates that a total of 221 200 individuals were newly diagnosed with lung cancer in 2015, representing approximately 13% of all new cancer diagnoses.1 Worldwide, lung cancer is the most commonly diagnosed malignancy. In their most recent report, WHO estimated that there were 1.8 million new lung cancer cases diagnosed in 2012.2

In addition to being one of the most commonly diagnosed cancers, survival from lung cancer is poor, making it the leading cause of cancer death in the USA.3 The 5-year lung cancer survival rate for cases diagnosed in 2011 was only 17.8%, with wide variations in survival rates by stage at diagnosis and specific histological subtype.4 The survival rate has only improved modestly in recent decades; the Surveillance, Epidemiology, and End Results (SEER) programme of the National Cancer Institute estimated that overall 5-year survival rates were 12.2% for cases diagnosed in 1975–1977, 13.0% for cases diagnosed in 1987–1989 and 14.6% for cases diagnosed in 1996–1998.4 Therefore, interventions or other strategies to increase survival are a source of consistent research, with a focus on lifestyle and treatment interventions.5 , …
PTU-030 10 Year Retrospective Review Of Abdominal Tuberculosis From A London Teaching Hospital: Diagnostic Methods: Abstract PTU-030 Table 1
Authors: JS Nayagam, C Mullender, A Poullis, C Cosgrove
Journal: Gut (2014)

<h3>Introduction</h3> Abdominal tuberculosis (TB) is difficult to diagnose, due to non-specific symptoms and radiological, histological and endoscopic similarity to other conditions. It can mimic Crohn’s disease and should always be considered as a differential diagnosis. There are significant risk of incorrectly diagnosing TB and committing patients to a prolonged course of toxic chemotherapy; or missing TB with public health implications and causing life-threathening disseminated TB when immunosuppressing patients. We sought to review the route to diagnosis of patients treated for abdominal TB, their sites of disease and the yield of various diagnostic modalities. <h3>Methods</h3> A retrospective review of patients treated at St George’s Hospital, London, for abdominal TB from June 2003 to August 2013 was conducted. Information was gained from electronic patient records and the hospital’s tuberculosis database. <h3>Results</h3> 65 cases of abdominal TB were identified. Average age was 42 years (range 18–97), with 49.2% females. Pre-diagnosis: 49.2% underwent endoscopy, 64.6% ultrasound, 70.8% CT, 3.1% MRI and 10.8% small bowel series. TB was cultured in 47.7% of patients, in the remaining 52.3% the diagnosis of abdominal TB was based on radiology, symptoms, suggestive histopathology, exclusion of other conditions or TB at another site. The site was: peritonitis in 35.4%, enteritis in 27.7%, solid organ TB in 3.1%, combination of sites in 33.8%. 24.6% had co-existent pulmonary TB isolated on sputum culture. The rate of culture positivity varied from modality of specimen acquisition as outlined in the table 1 case was resistant to isoniazid and streptomycin. <h3>Conclusion</h3> Confirming a diagnosis of abdominal TB is notoriously difficult, with the rate of positive culture below 50% in our series. Non-invasive imaging is commonly used and is useful to characterise the phenotype of abdominal TB and suggest sites for sampling, however it does not assist in obtaining a definitive diagnosis. Invasive testing is a cornerstone of diagnosis. Ascitic fluid and surgically acquired biopsies had a higher diagnostic rate than endoscopy. There was a low rate of endoscopic biopsies being sent for Microbiology. If TB is part of the differential diagnosis endoscopists must ensure microbiological samples are taken into normal saline solution and sent for mycobacterial culture. <h3>Disclosure of Interest</h3> None Declared.
Abstract 1064: MicroRNA-based diagnosis and therapy in NRF2-stabilized tumor
Authors: Jun Inoue, Naoto Fujiwara, Shinsuke Yamamoto, Tatsuyuki Kawano, Johji Inazawa
Journal: Cancer Research (2016)

Abstract NRF2 is a master transcriptional regulator that integrates cellular stress responses and is negatively regulated by KEAP1 at the posttranslational level. In human cancers, aberrantly stabilized NRF2, either by mutation of NRF2 or KEAP1, plays a vital role in chemoresistance and tumor cell growth through the transcriptional activation of target genes, suggesting that targeted inhibition of NRF2 is a potential therapy for NRF2-stabilized tumors. Some tumor-suppressing microRNAs (miRNAs) target multiple oncogenes concurrently and therefore may be useful as cancer therapeutic agents. Further, such miRNAs may be useful to address chemotherapeutic resistance in cancer, which remains a primary clinical challenge in need of solutions. Thus, cytoprotective processes upregulated in cancer cells that are resistant to chemotherapy are a logical target for investigation. By using a reporter-coupled miRNA library screening, we have recently identified four miRNAs (miR-507, -634, -450a, and -129-5p) that negatively regulate the NRF2 activity by directly targeting. Importantly, downregulation of these miRNAs, in addition to the somatic mutation of NRF2 or KEAP1, is associated with stabilized NRF2 and poor prognosis in esophageal squamous cell carcinoma (ESCC). Interestingly, we found that overexpression of miR-634 activates the mitochondrial apoptotic pathway by direct concurrent targeting of genes associated with mitochondrial homeostasis, antiapoptosis, and autophagy, together with NRF2-mediated antioxidant ability. In particular, we showed how enforced expression of miR-634 enhanced chemotherapy-induced cytotoxicity in a model of ESCC, where resistance to chemotherapy remains clinically problematic. Our findings illustrate how reversing miRNA-mediated cytoprotective processes may offer a broadly useful approach to improving cancer therapy. Citation Format: Jun Inoue, Naoto Fujiwara, Shinsuke Yamamoto, Tatsuyuki Kawano, Johji Inazawa. MicroRNA-based diagnosis and therapy in NRF2-stabilized tumor. [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 1064.
Effect of short term adjuvant intravesical chemotherapy on recurrence rates compared with one immediate postoperative intravesical chemotherapy in patients with non muscle invasive bladder carcinoma with low or intermediate recurrent risk.
Authors: Yoshio Naya, Masakatsu Oishi, Takashi Ueda, Hiroyuki Nakanishi, Terukazu Nakamura, Fumiya Hongo, Kazumi Kamoi, Koji Okihara, Tsuyoshi Iwata, Motohiro Kanazawa, Kazuya Mikami, Hiroaki Miyashita, Tsuneharu Miki
Journal: Journal of Clinical Oncology (2015)

e15523 Background: We present a randomized, prospective, multicenter study comparing one immediate postoperative intravesical chemotherapy with short-term adjuvant intravesical chemotherapy after transurethral resection of bladder tumor (TURBT) for non-muscle invasive bladder carcinoma (NMIBC) with low or intermediate recurrent risk. Methods: This study was a multicenter, prospective, randomized controlled trial, and was approved by the ethics committees of Kyoto Prefectural University of Medicine in September 2010. One hundred six patients with low or intermediate recurrent risk of NMIBC were randomized to one immediate postoperative intravesical instillation of pirarubicin (THP) 30mg (Group A), or additional intravesical chemotherapy of THP 30mg weekly for 8 weeks (Group B). The patients were examined by cystoscopy and urine cytological examination every 3 months after TURBt to determine bladder tumor recurrence. Results: The 2-year recurrence free rate were 65.3% for Group A and 87.2% for Group B, respectively (log rank test, p = 0.038). In patients with intermediate recurrent risk, the 2year recurrence free rate were 62.3% for Group A and 86.8% in group B, respectively (log rank test, p = 0.0261). There was no patient with progression during this period. Adverse events were documented in 0% and 24.4% in Group A and Group B, respectively. There was no patient with severe adverse event (Grade 3 or more). Conclusions: Additional instillation of THP 30mg weekly for 8 weeks reduced the risk of tumor recurrence without severe toxicity in NMIBC patients with intermediate recurrent risk. Our data provide a rationale for adjuvant intravesical chemotherapy after TURBT in NMIBC patients with intermediate recurrent risk.
Whole Exome Sequencing Detecting Kinesin Family Gene Defects In Myeloid Neoplasm
Authors: Chantana Polprasert, Hideki Makishima, Bartlomiej P Przychodzen, Naoko Hosono, Wenyi Shen, Dayong Huang, Yuichi Shiraishi, Satoru Miyano, Kenichi Yoshida, Seishi Ogawa, Jaroslaw P. Maciejewski
Journal: Blood (2013)
Abstract 2104: ERK-dependent IL-6 autocrine signaling mediates adaptive resistance to pan-PI3K inhibitor in head and neck squamous cell carcinoma
Authors: Mi Ran Yun, Han Na Kang, Byoung Chul Cho
Journal: Cancer Research (2016)

Abstract Purpose: To investigate resistant mechanisms to NVP-BKM120, a pan-PI3K inhibitor, and potential combination therapies in head and neck squamous cell carcinoma (HNSCC). Experimental Design: A panel of 10 human HNSCC cell lines including NVP-BKM120-resistant HNSCC patient-derived cell lines were used to evaluate the antitumor activity of NVP-BKM120. Patient-derived tumor xenograft (PDTX) models were established from recurrent/metastatic HNSCC patients treated with and resistant to NVP-BKM120. Results: Treatment of NVP-BKM120 led to upregulation of interleukin 6 (IL-6) and subsequent activation of either extracellular signal-regulated kinase (ERK) or signal transducers and activators of transcription 3 (STAT3), resulting in a modest antitumor effects on HNSCC cells. In a subset of cell lines, blockade of IL-6 autocrine signaling with IL-6 receptor (IL-6R) siRNA or IL-6R neutralizing antibody completely abolished constitutive or NVP-BKM120-induced activation of ERK and STAT3 as well as expression of oncogenic factors including Bcl2 and cMYC, resulting in the enhanced sensitivity to NVP-BKM120 with a marked reduction of S phase and significant increment of G0/G1 arrest. Interestingly, trametinib, a MEK inhibitor, significantly reduced NVP-BKM120-induced IL-6 and cMYC upregulation, whereas it had no effect on STAT3 inhibition. Moreover, combination of NVP-BKM120 with trametinib yielded more potent anti-tumor effects than combination with a pharmacologic inhibitor of STAT3 or siSTAT3. Furthermore, combination of NVP-BKM120 with trametinib or tocilizumab, a humanised anti-IL-6 receptor antibody, synergistically suppressed the growth of NVP-BKM120-resistant PDTX models as compared with either agent alone, which was confirmed in two PDTX-derived cell lines. Conclusions: Collectively, these results suggested that IL-6/ERK signaling contributes to intrinsic and adaptive resistance to NVP-BKM120 in HNSCC, providing a rationale for a novel therapeutic strategy to overcome resistance to pan-PI3K inhibitors. Citation Format: Mi Ran Yun, Han Na Kang, Byoung Chul Cho. ERK-dependent IL-6 autocrine signaling mediates adaptive resistance to pan-PI3K inhibitor in head and neck squamous cell carcinoma. [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 2104.
Optimizing chimeric antigen receptor (CAR) T cell therapy for adult patients with relapsed or refractory (r/r) acute lymphoblastic leukemia (ALL).
Authors: Noelle V. Frey, Pamela A Shaw, Elizabeth O. Hexner, Saar Gill, Katherine Marcucci, Selina M. Luger, James K. Mangan, Stephan A. Grupp, Shannon L. Maude, Solveig Ericson, Bruce Levine, Simon F. Lacey, Jan J. Melenhorst, Carl H. June, David L. Porter
Journal: Journal of Clinical Oncology (2016)

7002 Background: Genetically modified T cells expressing an anti-CD19 CAR result in response rates of 90% in children with r/r CD19+ ALL. Cytokine release syndrome (CRS) is the most significant treatment-related toxicity and usually responds to anti-cytokine therapy. We now report outcomes from 27 adults with r/r ALL, 3 who died with refractory CRS. Methods: Autologous T cells were transduced with a lentiviral vector encoding a murine anti-CD19 scFv/4-1BB/CD3ζ (CTL019) CAR. Adults with r/r CD19+ ALL received CTL019 on one of 2 trials (NCT02030847; NCT01029366). All pts received lymphodepletion followed by CTL019 as a 1-time infusion or fractionated infusions over 3 days (10%:D1, 30%:D2 and 60%:D3). Total planned CTL019 dose varied (5 x 107 - 5 x 108) with protocol modifications for CRS toxicity. Results: 27 pts (median age 44 (range 21-72); received CTL019 via 4 dosing cohorts (Table 1). 5 pts had primary refractory disease, 9 had prior blinatumomab, 9 had prior allogeneic SCT. 9 pts were tx with 5x107 CTLO19 cells with either a 1-time dose (n = 6) or fractionated dosing. 6/9 pts had Gr 3-4 CRS managed with tocilizumab and only 3 pts achieved a CR (33%). 6 pts were tx with a 1-time CTL019 dose of 5x108. 3/6 pts died with CRS refractory to tocilizumab and corticosteroids. These 3 pts also had concurrent culture positive sepsis. The other 3 pts achieved CR. 12 pts were then tx with a planned CTL019 dose of 5x108 administered via fractionated dosing. If early CRS was noted, subsequent infusions of CTL019 were held allowing for intra-patient dose modification. Anti-cytokine tx was initiated at Gr 3 CRS. 9/12 had manageable Gr 3-4 CRS with an ORR rate of 83% (9/12 CR; 1/12 PR). Conclusions: Higher doses of CTL019 may be more effective and split dosing may improve safety allowing for intra-patient dose modification without compromising efficacy in adult pts with r/r ALL. There is a high risk of fatal outcome with concurrent sepsis and CRS and measures to prevent infection and intervene early for CRS are warranted. Clinical trial information: NCT01029366.Cohort N CTL019 Dose Fractionation CRS ≥ Gr3 CRS Gr5 ORR 1-2 9 5x107 N/Y 6/9 0 33% 3 6 5x108 N 6/6 3 50% 4 12 5x108 Y 9/12 0 83%
Case 17-1989
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Gary R. Epler, Eugene J. Mark
Journal: New England Journal of Medicine (1989)

Presentation of CaseA 58-year-old man was admitted to the hospital because of fever, chills, night sweats, and cough.The patient was well until two or three months earlier, when he experienced the onset of malaise and easy fatigue, with a nonproductive cough and intermittent chest pain. Fever appeared, with occasional shaking chills and anorexia. During the months preceding entry the cough and chest pain worsened, and exertional dyspnea developed. One week before admission the temperature rose to 40°C, and he was no longer able to work. He was admitted to the hospital.Twenty years earlier the patient had worked . . .
Abstract LB-067: Proteomic analysis identifies multi-dimensional deregulated signaling pathways in SCLC lung cancer
Authors: Klarisa Rikova, Ben Hall, Tyler Levy, Anthony Possemato, Mike Aguiar, Sean Beausoleil, Jian Min Ren, Kimberly Lee Lee, Scott Lonning, Michael Comb
Journal: Cancer Research (2016)

Abstract Lung cancer is the most common type of cancer in the U.S., with 5 yr. survival rates of 18% and 6% for non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC) patients, respectively. In spite of success with targeted therapies for 15-20% of patients with NSCLCs, the success is generally short-lived as the tumors become resistant to treatment. In contrast to NSCLC, no successful targeted therapies have been identified in SCLC. Further understanding of the regulatory cell signaling networks for SCLCs, may enable the discovery of new actionable lung cancer drivers. Posttranslational modifications (PTMs), including phosphorylation, acetylation and methylation, act alone and in combination to regulate protein function, cellular behavior and epigenetics. All three types of PTMs are deregulated in various cancers. In this study we developed a highly quantitative MS/MS approach combining TMT labeling with a number of motif and site-specific antibodies to identify deregulated signaling pathways between tumor and normal specimens. PTM-specific antibodies were used to enrich modified peptides followed by 6-plex TMT mass-spec analyses to quantitatively measure over 15,300 differentially phosphorylated, acetylated, and methylated sites on over 4,600 proteins from 17 SCLC patient tissues and 5 para-normals. Understanding cell-signaling networks at the intersection of multiple pathways and protein modification systems in SCLC lung cancers leads to the identification of new druggable disease drivers. Citation Format: Klarisa Rikova, Ben Hall, Tyler Levy, Anthony Possemato, Mike Aguiar, Sean Beausoleil, Jian Min Ren, Kimberly Lee Lee, Scott Lonning, Michael Comb. Proteomic analysis identifies multi-dimensional deregulated signaling pathways in SCLC lung cancer. [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 LB-067.