tbuckley/cabot-search huggingface dataset:
Influence of obesity on survival in non-metastatic triple negative breast cancer; a retrospective analysis.
Authors: Suman Paul, Rachana Yendala, Naga Praneeth Raja, Iman Mohamed
Journal: Journal of Clinical Oncology (2016)

e12546 Background: Obesity has been linked with both increased incidence and poor outcome in hormone receptor positive breast cancer. However the effect of obesity in triple negative breast cancer (TNBC) which accounts for 20% of all breast cancers remains unclear. While early research (trials E1199 in 2008, E5188 in 2005) have shown little effect of body mass index (BMI) on TNBC prognosis, later trials (SUCCESS A trial 2015) demonstrated reduced survival in TNBC patients with obesity. This conflicting evidence warranted additional studies to evaluate the effect of obesity on TNBC prognosis. Methods: We performed retrospective study from data gathered from 74 patients diagnosed with non-metastatic TNBC and treated with anthracycline, cyclophosmamide and taxane based chemotherapy between 2004 and 2010 at the University of Toledo Dana Cancer Center. Patients were grouped as normal weight (BMI < 25.0), overweight (BMI 25.0-29.9), obese (BMI 30.0-39.9) and extremely obese (BMI > 40.0) based on NIH/NHLBI guidelines, and the effect of BMI on disease-free survival (DFS) and overall survival (OS) was evaluated. Median follow-up was 68 months Results: Cox regression analysis revealed that compared with normal weight patients, extremely obese patients (BMI > 40) demonstrated significantly reduced OS (hazard ratio (HR) 2.89, 95% confidence interval (CI) 1.14-7.33, p < 0.05) and reduced DFS (HR 2.25, 95% CI 1.02-4.93, p < 0.05). The survival rates of overweight patients (overall survival HR 4.7, CI 0.36-6.0, p = 0.23, disease-free survival HR 2.4 CI 0.24-2.49 p = 0.44) and obese patients (overall survival HR 2.55, CI 0.83-7.83, p = 0.1, disease-free survival HR 2.23, CI 0.76-7.09, p = 0.13) were not statistically different from survival rates of normal weight patients. Conclusions: Extreme obesity at time of diagnosis of non-metastatc TNBC significantly worsens prognosis when compared to that of patients with normal BMI. This effect of BMI on TNBC could represent an unrecognized effect of obesity related endocrine dysregulation and TNBC tumorigenesis.
OP0016 Osteoclast numbers in joints of rats with adjuvant arthritis are decreased by treatment with il-1ra and/or peg stnf-ri
Authors: U Feige, YL Hu, S Morony, G Campagnuolo, D Duryea, B Bolon
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Adjuvant arthritis (AdA) induced in Lewis rats by injection of mycobacteria in oil is characterised by marked inflammation and skeletal damage. Recent work by our group using the AdA model has shown that skeletal destruction is mediated by the osteoclast differentiation factor osteoprotegerin (OPG) ligand,<sup>1</sup> and that inhibition of bone loss is associated with anti-inflammatory efficacy.<sup>2</sup> <h3>Objectives</h3> The current study was performed to assess whether anti-inflammatory molecules act to spare bone by regulating intra-lesional numbers of osteoclasts. <h3>Methods</h3> AdA was induced in male Lewis rats (n = 6/group) on Day 0, and hind paw swelling developed on Day 9. Animals were treated for 7 days (Days 9–15) and then necropsied (Day 16). Therapy consisted of interleukin-1 receptor antagonist (IL-1ra) or pegylated soluble tumour necrosis factor receptor type I (PEG sTNF-RI), administered alone or in all possible combinations, at the following doses: IL-1ra, 0.2, 1.0 or 5.0 mg/kg/hr (by s.c. infusion); PEG sTNF-RI, 0.25, 1.0 or 4.0 mg/kg/day (s.c bolus). Osteoclasts were detected by an indirect immunohistochemical method for cathepsin K. Inflammation, bone erosion and osteoclast numbers were scored blindly using tiered, semi-quantitative grading scales. <h3>Results</h3> Dose-dependent reductions in inflammation, bone erosion and osteoclast scores were observed for high doses of both anti-cytokine therapies, whether given alone or in combination. <h3>Conclusion</h3> These data indicate that anti-inflammatory doses of IL-1ra and PEG sTNF-RI protect the structural integrity of arthritic joints by regulating osteoclast numbers. <h3>References</h3> Kong, <i>et al</i>. Nature 1999;402:304 Feige, <i>et al</i>. Cell Mol Life Sci. 2000;57:1457
A meta-analysis of the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor treatment in non-small-cell lung cancer patients.
Authors: Hongmei Xu, Kaitlyn Minchella, Diansong Zhou, Nidal Al-Huniti
Journal: Journal of Clinical Oncology (2016)

e20604 Background: Non-small cell lung cancer (NSCLC) accounts for approximately 85% of lung cancer cases. Tyrosine kinase inhibitors (TKI) targeting epidermal growth factor receptor (EGFR) mutations have been the driving force for the treatment of NSCLC in recent years. An important clinical question that arises within oncology drug development is whether we can use early clinical endpoints from phase II or even phase I studies to predict phase III overall survival (OS) outcome for a new treatment. Methods: The Pubmed database was searched for randomized clinical trials from 2010 to 2015. Only phase II or phase III trials using EGFR TKIs (gefitinib, erlotinib, afatinib, dacomitinib, and icotinib) for patients with advanced NSCLC were included. The trials were categorized by line of treatment (1st line, 2nd line or above) and by patient populations (unselected or molecularly selected (EGFR mutation)). Median progression free survival (PFS) and median OS, PFS hazard ratio (HR) and OS HR were analyzed using Spearman’s rank order correlation. Results: In total, 38 trials (68 arms) were identified for unselected and molecularly selected patient population. Out of those, 62 arms were on EGFR TKI treatment. The median number of patients in each arm was 71 (range: 18- 617). Of 38 trials, 30 were unselected, and 8 were molecularly selected trials. The correlation between median PFS and median OS or between PFS HR and OS HR was generally low for most of the trials. There was no significant difference in OS between monotherapy and combination (median OS: 9.2 vs 9.1 months). Strongest correlation between median PFS and OS was observed from the molecularly selected population (r2= 0.626). The median OS was higher in molecularly selected patients than those in unselected (16.7 vs. 8.7 months). Conclusions: There is no significant correlation between median PFS and OS for most of trials except for studies in EGFR molecularly selected patients, indicating PFS could be a reasonable predictor of OS in molecularly selected patients for TKI therapies.
A Retrospective Pilot Study of Longitudinal Molecular Discordance of Primary versus Recurrent Triple Negative Breast Cancer (TNBC).
Authors: Yuan Yuan, Xiwei Wu, Susan Yost, Jinhui Wang, Lu Yang, Leanne Goldstein, Zheng Liu, Yate-Ching Yuan
Journal: Journal of Clinical Oncology (2016)

e12558 Background: Metastatic TNBC is a heterogeneous disease with poor clinical outcome. Tumor evolution at molecular level through the process of disease progression is poorly understood. Paired genomic analysis of TNBC at time of initial diagnosis will be compared with recurrent/refractory disease. Methods: An IRB-approved protocol was established to retrospectively collect paired primary and recurrent/refractory TNBC tissue between 2002-2015, with 46 paired specimens identified. Planed analyses include miRNA profiling and mRNA profiling. Nucleic acid from six paired tissues were extracted with Qiagen AllPrep FFPE kit. The miRNA libraries were prepared and sequenced on Hiseq2500. Sequences were aligned to hg19 genome and miRNA expression levels were counted by in house built R scripts. Further pathway annotation was identified using Qiagen Ingenuity pathway analysis. Validation for potential biomarkers was performed using TCGA TNBC patient cohort (n = 135). ANOVA and Kaplan Meier overall survival analysis using in house implemented R Bioconductor scripts was completed. Results: We have identified several miRNA from our preliminary statistical filtering small cohorts and validated using TCGA normal (n = 104) and TNBC (n = 135) with more than 4 fold expression changes. P-value less than 0.001 were up-regulated in TNBC such as miR-183, miR200c, and miR-203. These miRNA are involved in regulation of cell cycles and apoptosis. Let-7b, 125b-1, and 99a were down-regulated in our recurrent tumor samples. Results were further validated using TCGA with more than 3 fold significant decrease in TNBC compared to normal breast samples. Statistically significant differentially-expressed miRNAs identified from our TNBC patient cohort will be validated using TCGA. Conclusions: A number of miRNAs with differential expression between primary and paired recurrent TNBC tumor specimens were validated using NCI TCGA TNBC patient genomic profiling. Further analyses will be performed to understand the underlying molecular pathways. Parallel analyses of mRNAprofiling for molecular subtyping will be performed.
Anti-CD30-lentiviral targeted gene therapy approach for Hodgkin's lymphoma
Authors: Quang Luong, Kouki Morizono, Irvin Chen, Sven de Vos
Journal: Cancer Research (2007)

921  Combination chemotherapy for the treatment of Hodgkin lymphoma (HL) has a current success rate of over 85%, however, there still remains an unresolved problem of chemotherapy-resistant disease with most of these patients eventually dying due to progression. CD30 is a 120-kDa transmembrane glycoprotein belonging to the tumor necrosis factor (TNF)-receptor superfamily and is highly expressed on HL Reed-Sternberg cells; hence HL is an ideal disease for targeted therapy. We propose that specific, antibody-mediated, CD30-directed delivery of lentiviral vector constructs, encoding for a lethal cellular toxin, will be an effective anti-lymphoma strategy. However, gene delivery based therapy is limited by the transduction of non-target cells. The technology developed by Morizono et al. [Cell Cycle 2005(4); Nature Medicine 2005(11)] demonstrated that lentiviruses could be specifically and effectively directed to target cells by conjugation of an antibody to a modified ZZ Sindbis viral envelope (m168). For this study, we used HL cell lines (CD30+: L591, L428, Hs445, RPMI6666) and Burkitt lymphoma (BL) cell lines (CD20+/CD30-: Raji, Ramos). We show that conjugation of an anti-CD30 antibody to m168 (m168αCD30) results in specific targeting and transduction of CD30+ Hodgkin lymphoma cells while avoiding CD30- Raji and Ramos cells [range 11-83% for HL cells versus 1-4% for BL cells]. Similarly, targeting of CD20+ cells can be achieved. Several of our HL cell lines (L591, Hs445 and RPMI6666) are CD30+/CD20+ [range 11-25% by flow cytometry] and we demonstrate that we can equally transduce these cells with an anti-CD20 antibody (m168αCD20) conjugated to our lentivirus [range 11-30% for CD20+ HL cells; 3% for L428 cells; 40-47% for BL cells]. In addition, re-targeted viruses can transduce a greater percentage of L591 target cells than an unmodified virus (VSVG) [83% for m168αCD30 versus 43% for VSVG]. Our data clearly demonstrate that the efficacy and specificity of targeted therapy can be greatly enhanced, and lay the foundation for the development of more stable anti-CD30 directed lentiviral constructs expressing cellular toxins.
Risk, persistence, and multiplicity of HPV infections among HIV-negative and HIV-positive Nigerian women.
Authors: Sally Nneoma Adebamowo, Toyosi Olawande, Ayo Famooto, Eileen Dareng, Richard Offiong, Clement Adebamowo
Journal: Journal of Clinical Oncology (2016)

1565 Background: The incidence prevalence, persistence and multiplicity of high-risk HPV infection is different comparing HIV-positive to HIV-negative women. We examined the association between HIV and HPV infections among women in a prospective cohort in Nigeria. Methods: We enrolled women presenting at cervical cancer screening programs in Abuja, between 2012 and 2014 and collected information on demography, risk factors of HPV infection and cervical exfoliated cells samples at baseline and 12 months follow-up visits. DNA enzyme immunoassay (DEIA) and Roche Linear Array HPV Genotyping Test were used to characterize HPV. Persistent HPV infection was defined as positive results on 2 consecutive DEIA tests. Logistic regression models were used to estimate the association between HIV and risk of HPV infections. Results: Among the 1020 women enrolled, the mean age (±SD) was 37(8), 44% and 56% were HIV+ and HIV-, respectively. In the study population, HPV52 and 35 were the most common HPV types; the prevalence was 34% for any HPV, 24% for persistent HPV and 9% for multiple HPV infections; these were higher among HIV+ women (p-value < 0.001). The multivariate odds ratio (OR) and 95 % CI comparing HIV+ to HIV- women was 6.29 (95% CI 3.64 – 10.87, p-value < 0.001) for any high-risk HPV; 6.22 (95% CI 3.02 – 12.83, p-value < 0.001) for persistent high-risk HPV; and 6.46 (95% CI 2.69 – 15.52, p-value < 0.001) for multiple high-risk HPV infections. Conclusions: HIV infection is associated with increased risk of persistence and multiplicity of low-risk and high-risk HPV infections. These findings may explain in part, the increased risk of cervical cancer among women with HIV infections. Odds ratios and 95% CI of high-risk (HR) HPV infections by HPV status. HIV Negative HIV Positive P-value n = 427 n = 535 Risk of HR-HPV Infections Age Adjusted 1.00 6.49 (3.99 – 10.56) < 0.001 Model 1 1.00 6.21 (3.73 – 10.34) < 0.001 Model 2 1.00 6.29 (3.64 – 10.87) < 0.001 Persistence of HR-HPV Infections Age Adjusted 1.00 5.80 (3.04 – 11.06) < 0.001 Model 1 1.00 6.18 (3.14 – 12.19) < 0.001 Model 2 1.00 6.22 (3.02 – 12.83) < 0.001 Multiplicity of HR-HPV Infections Age Adjusted 1.00 8.66 (3.84 – 19.52) 0.01 Model 1 1.00 8.52 (3.67 – 19.82) 0.01 Model 2 1.00 6.46 (2.69 – 15.52) 0.05
Role and Mechanisms of Rhoa G17V in the Pathogenesis of AITL
Authors: Jose R Cortes, Alberto Ambesi-Impiombato, Lucile Couronne, Christine S Kim, Zachary West, Laura Belver, Ana Carolina da Silva Almeida, Govind Bhagat, Olivier A. Bernard, Adolfo A. Ferrando, Teresa Palomero
Journal: Blood (2016)
Clinical and Biological Implications of CUX1 Mutations in Myeloid Neoplasms
Authors: Mai Aly, Naoko Hosono, Przychodzen Bartlomiej, Hideki Makishima, Nagata Yasunobu, Cassandra M. Hirsch, Mikkael A. Sekeres, Jaroslaw P. Maciejewski
Journal: Blood (2016)
Poor awareness of colorectal cancer symptoms; a preventable cause of late presentation?
Authors: AT Manning, CYJ Chan, R Waldron, K Barry
Journal: Endoscopy (2005)

Aims: Awareness of colorectal cancer (CRC) symptoms leads to earlier presentation with increased potential for curative treatment. We aimed to review disease stage and duration of symptoms in patients diagnosed with CRC over a two year period, and to assess knowledge of CRC symptoms among outpatient attendees.
Changes in Coronary Artery Plaque With Testosterone Therapy—Reply
Authors: Matthew J. Budoff, Susan S. Ellenberg, Peter J. Snyder
Journal: JAMA (2017)

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Accuracy of Fine Needle Cytology in Histological Prediction of Papillary Thyroid Carcinoma Variants: a Prospective Study
Authors: Anna Cipolletta Campanile, Maria Gabriella Malzone, Nunzia Simona Losito, Gerardo Botti, Maria Grazia Chiofalo, Antongiulio Faggiano, Roberta Siciliano, Annamaria Colao, Luciano Pezzullo, Franco Fulciniti
Journal: Endocrine Pathology (2017)
Primary brain tumor and risk of venous thromboembolism.
Authors: Ashish Dutta Dwary, Ankita Gupta, Gary Von Burton, Prakash Peddi
Journal: Journal of Clinical Oncology (2017)

e13518 Background: Venous thromboembolism (VTE) is frequently associated with primary brain tumors (PBT). Brain tumors have been associated with higher rates of VTE in multiple studies. Studies comparing VTE incidence in meningioma (MEN), astrocytoma (AA), oligodendroglioma (OG) and glioblastoma multiforme (GBM) are lacking. The aim of this retrospective study is to report the VTE outcomes in all of the above brain tumors. Methods: Retrospective data from 476 patients with PBTs diagnosed between 1995-2015 at Louisiana State University Health Sciences Center-Shreveport was analyzed. The incidence of VTE (deep vein thrombosis or pulmonary embolism) was studied in these patients. Results: Out of 476 patients, 298 were females and 179 were male. One hundred and twenty seven (127) patients had GBM, 52 had AA, 33 had OG and 264 had MEN. Only two patients out of 264 with MEN had VTE (one patient had central line catheter associated DVT). VTE incidence did not correlate with the type of primary treatment i.e surgery verses radiation verses observation in this patient group. The incidence of VTE was 7.8 % in GBM patients. The risk of VTE in AA and OG patients were 7.7% and 9.0 % respectively. The VTE event in the OG, AA and GBM occurred during all phases of treatment including inpatient hospitalization for surgical resection, during concurrent chemo-radiation and in maintenance phase. Biopsy versus partial resection versus complete resection of GBM didn’t correlate with VTE occurrence. Conclusions: VTE is prevalent among adult patients with both low and high grade glial tumors. The thrombotic events occur during all phases of therapy indicating hypercoagulable state for many patients. Life-long anticoagulation may be necessary in these patients with thrombotic events. Thrombotic events in patients with MEN, however, are rare ( &lt; 1%). MEN do not appear to be a hypercoagulable and life-long anticoagulation is probably unnecessary in those with VTE.
The Na+-dependent chloride-bicarbonate exchanger SLC4A8 mediates an electroneutral Na+ reabsorption process in the renal cortical collecting ducts of mice
Authors: Françoise Leviel, Christian A. Hübner, Pascal Houillier, Luciana Morla, Soumaya El Moghrabi, Gaëlle Brideau, Hatim Hassan, Mark D. Parker, Ingo Kurth, Alexandra Kougioumtzes, Anne Sinning, Vladimir Pech, Kent A. Riemondy, R. Lance Miller, Edith Hummler, Gary E. Shull, Peter S. Aronson, Alain Doucet, Susan M. Wall, Régine Chambrey, Dominique Eladari
Journal: Journal of Clinical Investigation (2011)
Donor SIRPα polymorphism modulates the innate immune response to allogeneic grafts
Authors: Hehua Dai, Andrew J. Friday, Khodor I. Abou-Daya, Amanda L. Williams, Steven Mortin-Toth, Matthew L. Nicotra, David M. Rothstein, Warren D. Shlomchik, Takashi Matozaki, Jeffrey S. Isenberg, Martin H. Oberbarnscheidt, Jayne S. Danska, Fadi G. Lakkis
Journal: Science Immunology (2017)

Mice devoid of T, B, and natural killer (NK) cells distinguish between self and allogeneic nonself despite the absence of an adaptive immune system. When challenged with an allograft, they mount an innate response characterized by accumulation of mature, monocyte-derived dendritic cells (DCs) that produce interleukin-12 and present antigen to T cells. However, the molecular mechanisms by which the innate immune system detects allogeneic nonself to generate these DCs are not known. To address this question, we studied the innate response of Rag2-/- γc-/- mice, which lack T, B, and NK cells, to grafts from allogeneic donors. By positional cloning, we identified that donor polymorphism in the gene encoding signal regulatory protein α (SIRPα) is a key modulator of the recipient's innate allorecognition response. Donors that differed from the recipient in one or both Sirpa alleles elicited an innate alloresponse. The response was mediated by binding of donor SIRPα to recipient CD47 and was modulated by the strength of the SIRPα-CD47 interaction. Therefore, sensing SIRPα polymorphism by CD47 provides a molecular mechanism by which the innate immune system distinguishes between self and allogeneic nonself independently of T, B, and NK cells.
Outcome of Immune-Suppressive Therapy (IST) and Hematopoietic Stem Cell Transplantation (SCT) in Patients with Aplastic Anemia: A Retrospective Single Center Experience
Authors: Onyee Chan, Onyemaechi Okolo, Muhammad Husnain, Irbaz Bin Riaz, Faiz Anwer
Journal: Blood (2016)
Durable complete responses observed in IDH1 mutated high grade glioma at first recurrence undergoing treatment with Toca 511 and Toca FC.
Authors: Timothy Francis Cloughesy, Derek Ostertag, Joseph C. Landolfi, Tobias Walbert, Michael A. Vogelbaum, J. Bradley Elder, Steven Bloomfield, Bob Carter, Clark Chen, Steven N. Kalkanis, Santosh Kesari, Albert Lai, Ian Lee, Linda M. Liau, Tom Mikkelsen, Phioanh Leia Nghiemphu, David Eric Piccioni, Douglas J. Jolly, Harry E. Gruber, Asha Das
Journal: Journal of Clinical Oncology (2017)

e13504 Background: Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector (RRV). RRVs selectively infect cancer cells due to cell division requirements for virus integration into the genome and defects in innate and adaptive immune responses found in cancers that support virus replication. Toca 511 spreads through cancer cells and stably delivers the gene for an optimized yeast cytosine deaminase that converts the prodrug Toca FC (an investigational, extended-release formulation of 5-fluorocytosine) into 5-fluorouracil (5-FU). 5-FU kills infected cancer cells that are dividing, diffuses and kills surrounding cancer cells as well as myeloid derived suppressor cells and tumor associated macrophages, thus reestablishing immunity to tumor. Methods: In this phase 1 trial (NCT01470794), ascending doses of Toca 511 were injected into the resection bed of patients with recurrent high grade glioma undergoing resection, followed by oral administration of courses of Toca FC 5-7 weeks after Toca 511 injection. Additional cohorts included combination of Toca 511 &amp; Toca FC with bevacizumab or lomustine. Results: Objective responses (ORs) are observed in IDH1 wildtype (wt) and mutant (mt) phenotypes, including 3 complete responses (CRs) (2 IDH1 mt and 1 IDH1 wt) and 2 partial responses (2 IDH1 wt) for patients treated with Toca 511 &amp; Toca FC, and 1 CR (1 IDH1 mt) for a patient treated with Toca 511 &amp; Toca FC and bevacizumab. ORs are observed 6-19 months after Toca 511 injection and are consistent with an immunologic mechanism. Median time to initial response is 9.2 months; median duration of response (mDOR) is 25.2 months. Excluding the combination cohorts, mDOR is 26.7 months. All responders are alive 21.2+ to 42.6+ months, suggesting a correlation of OR and OS. An additional radiologic CR is observed in 1 IDH1 mt patient at 1st recurrence who received intravenous Toca 511 plus injection into the resection bed. All 4 IDH1 mt patients treated at 1st recurrence had CRs. Conclusions: There may be an association between ORs and IDH1 mutation with Toca 511 &amp; Toca FC treatment. Updated clinical benefit, molecular profiles and tumor mutational load are reported. Clinical trial information: NCT01470794.