tbuckley/cabot-search huggingface dataset:
Human antigen R as a predictive marker for response to gemcitabine-based chemotherapy in advanced cisplatin-resistant urothelial cancer.
Authors: Yasuyoshi Miyata, Kensuke Mitsunari, Akihiro Asai, Tomohiro Matsuo, Kojiro Ohba, Hideki Sakai
Journal: Journal of Clinical Oncology (2016)

421 Background: In patients with advanced urothelial cancer (UC), a combined therapy of cisplatin (CDDP) and gemcitabine (GEM) is the most commonly used first (1st)-line systematic chemotherapy. Although no regimen for CDDP-resistant UC has been established, GEM-based regimens are often used in these patients. In other cancers, HuR status in cancer cells is closely associated with response to GEM. The aim of this study was to establish the predictive value of HuR expression for disease progression and survival in UC patients treated with GEM-based regimens as 1st or second (2nd)-line chemotherapy. Methods: Fifty patients with advanced UC were included in the study. As 1st-line chemotherapy, MVEC (methotrexate, vinblastine, epirubicin, and CDDP) and GC therapy were performed in 34 (68.0%) and 16 patients (32.0%), respectively. After progression, 45 patients (90.0%) were treated with combined GEM and paclitaxel (PTX) therapy, and 5 patients (10.0%) were treated with GEM monotherapy. Cytoplasmic and nuclear Human antigen R (HuR) expression was evaluated using immunohistochemical techniques. The relationships between HuR expression and local response and outcome were analyzed. Results: In 1st-line chemotherapy, no anti-cancer effects were associated with nuclear or cytoplasmic HuR expression. In 2nd-line chemotherapy, although nuclear HuR expression also had no significant relationship to anti-cancer effects, local tumor response was significantly better if there was positive cytoplasmic HuR expression (P = 0.002). Multivariate analyses revealed that cytoplasmic HuR expression was a significant predictive marker for longer overall survival (hazard ratio, 0.22; 95% confidential interval, 0.09–0.56; P = 0.001). There is no significant relationship between nuclear HuR expression and parameters of anti-cancer effects. Conclusions: Cytoplasmic HuR expression is a significant predictive marker of response to GEM-based chemotherapy in CDDP-resistant UC. Despite limitations of a small retrospective study, our results might have important information to discuss the treatment strategies and warrant further basic and clinical research.
Long-lasting hematologic remission with imatinib therapy in idiopathic hypereosinophilic syndrome (HES) associated with lymphomatoid papulosis (LP): Case report.
Authors: L. Curreli, A.D. Palmas, G.C. Latte, P. Lai, A. Gabbas
Journal: Journal of Clinical Oncology (2010)

e17004 Background: We report the case of a 32-year-old male patient (pt) with HES associated with LP. Presenting symptoms were fever, hyperleukocytosis and cutaneous lesions at lower limbs. Pt received Hydroxiurea (HU) as the first line chemotherapy achieving about one year of disease control. Due to echocardiographic detection of bilateral ventricular thrombosis LMW Heparin and then warfarin were also started. LP disappeared on 1999, while therapeutic adjustments were required to maintain only a partial control of HES despite therapy-related toxicities : 1) HU plus alfa IFN ; 2) HU plus PUVA-therapy plus methotrexate. October 9, 2001 pt was admitted in the hospital because of high grade fever, poor general conditions, dyspnoea, cough and diffuse bone pain. Hematologic evaluation revealed leucocytosis (230 × 109/L), with eosinophilia (about 195 × 109/L). 6-Thioguanine, HU and broad spectrum antibiotic therapy was started, but general conditions worsened by hypotension, high grade fluid retention, dyspnoea, asthenia, adynamia, epigastralgia, hepatomegaly and severe liver pain. Left ventricular ejection fraction (LVEF) decreased to 50% and bilateral ventricular thrombosis appear again. Ten days course of low dose-Ara-C decreased leucocyte count without clinical benefit. Methods: October 26, 2001, on the basis of a recent literature report (Schaller JL and Burkland GA, Case report: rapid and complete control of idiopathic hypereosinophilia with imatinib mesylate. MedGenMed.2001 Sep 7;3[5]:9.), pt received salvage therapy with imatinib 100 mg daily. Detailed informed consent was previously obtained. Results: Quick onset and very impressive disease response was observed with an hematologic remission achieved after 4 days of therapy. General conditions, heart performance (LVEF 65%) and LV global kinetic were all improved. Until now pt maintains a complete hematologic remission lasting more than 98 months with a good heart performance. Maintenance therapy with daily imatinib 100 mg is still ongoing without side effects. Conclusions: Our finding confirms that imatinib may be an useful therapeutic tool in the treatment of some cases of HES. No significant financial relationships to disclose.
Abstract 1696: Mitochondrial haplotype alters metastasis in a non-cell autonomous manner
Authors: Amanda E. Brinker, Carolyn J. Vivian, Danny R. Welch
Journal: Cancer Research (2016)

Abstract Mitochondrial Nuclear Exchange (MNX) mice, created by transferring the nucleus from an oocyte from strain x into an enucleated oocyte of strain y, showed that mammary tumor formation and metastasis can be regulated by inherited mitochondrial polymorphisms (PMID26471915). Besides genetic (cell autonomous) changes observed, we asked whether mitochondrial polymorphisms in non-cancer compartments could exert effects on tumor formation or metastasis. Tumor cells were injected into syngeneic wild type mice and tumor growth and metastasis were compared to similarly injected cells into MNX mice sharing the same nuclear but different mtDNA backgrounds. Orthotopic tumor growth rates were equal for all of the cell lines tested. However, the ability to form experimental lung metastases following i.v. injection were dramatically altered. Compared to injections into wild-type, syngeneic mice, E0771 mammary carcinoma and B16-F10 melanoma cells (both syngeneic to C57BL/6J), formed significantly (P&amp;lt;0.01) more lung metastases in C57BL/6J-mtMNX(C3H/HeN) and K1735-M2 melanoma cells (syngeneic to C3H/HeN) formed significantly fewer lung metastases in C3H/HeNmtMNXC57BL/6J. These results have been replicated at least three times using &amp;gt;10 mice per experiment. Interestingly, C57BL/6J mitochondria confer resistance to metastasis in both cell autonomous and non-cell autonomous experiments. Basal metabolic differences comparing mouse embryonic fibroblasts isolated from wild-type and MNX mice are among mechanisms being explored. Together, our findings highlight the striking influences that mitochondrial haplotypes can exert on tumorigenicity and metastasis via both intrinsic and extrinsic mechanisms. Support: Susan G. Komen for the Cure (SAC11037), Natl Fndn Cancer Res, Steiner Family Fund for Metastasis Research, Kansas Bioscience Authority, CA134981, P30-CA168524 Citation Format: Amanda E. Brinker, Carolyn J. Vivian, Danny R. Welch. Mitochondrial haplotype alters metastasis in a non-cell autonomous manner. [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 1696.
The impact of HLA-matching on reduced intensity conditioning regimen unrelated donor allogeneic stem cell transplantation for acute myeloid leukemia in patients above 50 years—a report from the EBMT acute leukemia working party
Authors: Marie T. Rubio, Bipin N. Savani, Myriam Labopin, Emmanuelle Polge, Dietger Niederwieser, Arnold Ganser, Rainer Schwerdtfeger, Gerhard Ehninger, Jürgen Finke, Arnold Renate, Charles Craddock, Nicolaus Kröger, Michael Hallek, Pavel Jindra, Mohamad Mohty, Arnon Nagler
Journal: Journal of Hematology & Oncology (2016)

Data comparing fully matched and mismatched-unrelated-donor (M- and mM-URD) allogeneic hematopoietic stem cell transplant (allo-SCT) following reduced intensity conditioning regimens for acute myeloid leukemia are limited. We retrospectively compared the outcome of 3398 patients above the age of 50 years who underwent 10/10 M-URD (n = 2567), 9/10 (n = 723), or 8/10 (n = 108) mM-URD allo-SCT for acute myeloid leukemia after reduced intensity conditioning regimen between 2000 and 2013. The Kaplan-Meier estimator, the cumulative incidence function, and Cox proportional hazards regression models were used where appropriate. HLA matching had no impact on engraftment (p = 0.31). In univariate analysis, in comparison to 10/10 M-URD, mM-URD was associated with higher incidence of grade II–IV acute graft-versus-host disease (GVHD) (p = 0.0002), similar rates of chronic GVHD (p = 0.138) but increased incidence of its extensive form (p = 0.047). Compared to 10/10 M-URD, patients transplanted in the first complete remission (CR1) with a 9 or an 8/10 mM-URD had decreased 2-year leukemia free (LFS) (p = 0.005) and overall survivals (OS) (56.7, 46.1, and 50.2 %, respectively, p = 0.005), while outcomes were comparable between all groups for patients transplanted beyond CR1. In multivariate analysis, 9/10 versus 10/10 URD was associated with higher non-relapse mortality (HR 1.34, p = 0.001), similar risk of relapse and chronic GVHD and inferior LFS (HR 1.25, p = 0.0001), and OS (HR 1.27, p = 0.0001). There was no difference in adjusted transplant outcomes between 9/10 and 8/10 mM-URD. Reduced intensity conditioned allo-SCT with a 10/10 M-URD remains the preferable option for AML patients above the age of 50 years. The use of a 9/10 or an 8/10 mM-URD in patients not having a fully matched donor represents an alternative therapeutic option that should be compared to other alternative donor transplant strategies.
On Risk Estimation versus Risk Stratification in Early Prostate Cancer
Authors: Sigrid V. Carlsson, Michael W. Kattan
Journal: PLoS Medicine (2016)

Clinically localized prostate cancer (PC) is a heterogeneous disease with highly variable clinical outcome.When counseling a patient with PC, the clinician ought to provide outcome probabilities as accurately as possible, given the patient and data at hand.Here is where the clinical question becomes a statistical one: what is the long-term prognosis and marginal benefit of treatment A versus treatment B versus no treatment-and in relation to death from other causes?Although randomized trials are under way (e.g., UK ProtecT trial), we do not have data on long-term outcomes comparing radical prostatectomy (RP), radiotherapy (RT), and active surveillance (AS) to provide patients with these numbers.To help clinicians communicate prognostic information and guide appropriate management for the patient, a wide array of risk assessment tools combining clinical and pathologic variables are available [1].Risk categories typically combine stage, grade, and prostate-specific antigen (PSA) concentration into categorizations such as "low," "intermediate," or "high" risk.One of the most commonly used is the D'Amico (1998) risk classification system [2], but limitations include significant heterogeneity, i.e., a wide range in risk of biochemical recurrence (BCR) within each risk group stratum-compared with predicting risk using a mathematical formula-and considerable overlap in risk between the intermediate-and high-risk groups [3].A modified risk stratification scheme adopted by the National Comprehensive Cancer Network (NCCN) incorporates very low-and very high-risk groups, number of prostate biopsy cores positive, percent cancer core involvement, and PSA density, but is still limited by heterogeneity in recurrence within the risk strata [4].Recently, novel tissue-based molecular biomarkers have been developed to help sub-stratify risk based on tumor biology [5].Other means of classifying risk include probability tables, such as the Partin tables [6], which combine variables (stage, grade, PSA) into simple-to-use look-up tables, and risk scores, such as the University of California, San Francisco (UCSF)-Cancer of the Prostate Risk Assessment (CAPRA) score [7], which calculates risk through a summation of points for each variable in a total score of 0-10.However, risk strata are often collapsed; for example, the Gleason score (GS) is often re-categorized into a three-tiered grouping (6, 7, and 8-10).In addition, because of the range of the scale (from 6 to 10), some patients misinterpret the lowest score (GS 6) as a "middle" score.Communication of risk then becomes an inaccurate reflection of prognosis and could make some patients with low-risk disease opt for primary treatment over initial expectant management.Also, GS 7 is sometimes used as a single score, when 3+4 = 7 or 4+3 = 7 have been shown to be prognostically different; the first number indicates the predominant, or most a11111
The effect of erlotinib after gefitinib failure in advanced non-small cell lung cancer (NSCLC) patients with poor performance status (PS): A matched-pair case-control study.
Authors: M. Huang, D. Luo, X. Zhang, M. Yu, B. Zou, Y. Li, J. Long, J. Wang, F. Peng, Y. Xu, L. Li, L. Ren, M. Hou, Y. Lu
Journal: Journal of Clinical Oncology (2011)

e18057 Background: Gefitinib plays an important role in non-small cell lung cancer (NSCLC) treatment. However, most patients have disease progressed even after obtaining an initial response, and the role of erlotinib treatment after gefitinib failure remains to be debated, especially in those heavily treated with poor performance status (PS). Therefore a retrospective matched-pair case-control study was carried out to evaluate the role of erlotinib after gefitinib failure in patients with advanced NSCLC. Methods: A total of 58 patients were identified at West China Hospital from May 2005 to July 2009. The two groups were balanced according to nine variables: age, gender, smoking history, stage, histopathology, number of prior systemic chemotherapy regimens before gefitinib, tumor response to gefitinib, ECOG performance score before erlotinib or BSC, number of prior systemic therapies before erlotinib or BSC. EGFR genotypes were detected by the amplification refractory system. Results: All patients had PS ≥2 scores and almost all patients (89.7%) accepted more than two systemic therapies before erlotinib or BSC while 75% of the patients with PS=2 scores had received more than three systematic therapy regimens. The EGFR genotypes were detected in 36 (62.1%) patients, 19 of them were in the erlotinib group. Median overall survival (OS) for the total 58 patients was 6 months. Median OS for patients received erlotinib and BSC was 10 and 3 months, respectively (P=0.001). Disease control rate (DCR) and objective response rate (ORR) were 51.7% and 10.3% in patients received erlotinib, respectively, while median time to progression (TTP) of 3 months was obtained. Among 19 patients of the erlotinib group with biomarker results available, those with EGFR mutation achieved significant longer median TTP (9.3 months vs. 3.0 months, P=0.016) and better DCR (83.3% vs. 46.2%, P=0.177) than those with wild-type EGFR. Conclusions: a switch to erotinib after gefitinib failure improved OS in advanced NSCLC patients with poor PS, and the patients with EGFR mutation seemed to be associated with better survival.
Abstract 2466: Development of a novel gene targeting and clone screening platform to engineer common pediatric glioma mutations into model cell lines
Authors: Nathan R. Fons, Yulia Surovtseva, Gregory A. Breuer, Ranjini K. Sundaram, Ranjit S. Bindra
Journal: Cancer Research (2016)

Abstract The utility of CRISPR/Cas9 gene targeting tools to alter endogenous genomic loci has revolutionized biomedical research across numerous disease focus areas, with especially large gains made in the development of disease models. However, the introduction of specific mutations using CRISPR/Cas9 can be associated with low yields of single cell clones harboring the desired homozygous or heterozygous mutations. Conventional clone screening methods can be a labor intensive and expensive process and thus, better approaches are needed to identify cells with the desired genotype(s). In parallel, there is a dearth of human tumor cell model systems for pediatric cancers, especially for Diffuse Intrinsic Pontine Glioma (DIPG). To address these needs, we recently designed and validated a platform which utilizes a novel, inducible Cas9 expression system coupled with a high-resolution DNA melt (HRM) analysis protocol to rapidly identify mutant clones. We applied our platform to model several common DIPG mutations, including truncating mutations within exon 6 of the gene, protein phosphatase 1D (PPM1D). Using our HRM analysis protocol, clones containing activating mutations in PPM1D were detectable and grouped distinctly from wild-type and non-functional clones; as validated through conventional Sanger sequencing and Ion Torrent Next Generation Sequencing. Importantly, multiple PPM1D mutant clones were generated in an expedited manner (&amp;lt; 4 weeks), using our unique HRM process-flow. We subsequently validated these clones in a collection of secondary assays, and we confirmed that the mutant proteins were functionally active. Several unique findings were identified in these studies, including substantial cell cycle-associated defects and basal activation of key proteins in the DNA damage response network. To our knowledge, we have created the first set of astrocyte cell lines harboring engineered PPM1D mutations at the endogenous gene locus. We are now testing these cell lines in high-throughput synthetic lethal screens to identify novel inhibitors of PPM1D-mutant DIPG tumors. These findings highlight the utility and power of our unique approach to rapidly create pertinent mutant cell lines for use in mutation-targeted biological assays. Our platform likely will become an invaluable tool for the development of better pediatric glioma cell line models in the future. Citation Format: Nathan R. Fons, Yulia Surovtseva, Gregory A. Breuer, Ranjini K. Sundaram, Ranjit S. Bindra. Development of a novel gene targeting and clone screening platform to engineer common pediatric glioma mutations into model cell lines. [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 2466.
Clinical Profile of Single-Agent Oprozomib in Patients (Pts) with Multiple Myeloma (MM): Updated Results from a Multicenter, Open-Label, Dose Escalation Phase 1b/2 Study
Authors: Ravi Vij, Michael Savona, David S. Siegel, Jonathan L. Kaufman, Ashraf Badros, Irene M. Ghobrial, Agne Paner, Sundar Jagannath, Andrzej Jakubowiak, Joseph R. Mikhael, Prashant Kapoor, Linda L. Neuman, Ju RueyJiuan Lee, Jesus G. Berdeja
Journal: Blood (2014)
Abstract 2231: IO125 is a potent inducer of tumor immunogenicity
Authors: Sanghamitra Mylavarapu, Shelly Kaushik, Yashpal Yadav, Monideepa Roy, Aniruddha Sengupta, Shiladitya Sengupta
Journal: Cancer Research (2016)

Abstract Combinatorial treatments with chemotherapeutics and immunotherapies are currently being investigated in several cancers. Chemotherapeutics can increase the immunogenicity of tumors besides modulating the immune system. Here we describe the development of a novel platinum-based therapeutic, IO-125, which assembles into stable nanoscale supramolecular structures. IO125 demonstrates enhanced activity compared with standard Pt drug across cancer lines. IO-125 preferentially targets tumors in vivo, and demonstrated improved efficacy in triple negative breast cancer (4T1), Lewis lung carcinoma (LLC) and melanoma (B16/F10) tumor models. Treatment with IO-125 elevates expression of immune-markers (including IGKC, PD-L1, PD-1, CD8A), which are associated with good prognosis. In addition, combinatorial treatment with IO-125 and antibody against immune checkpoint inhibitor(s) resulted in superior antitumor efficacy compared to treatment with antibody alone. This study shows that supramolecular therapeutics, especially IO125, can emerge as a novel approach to focally modulate the tumor immune contexture. Citation Format: Sanghamitra Mylavarapu, Shelly Kaushik, Yashpal Yadav, Monideepa Roy, Aniruddha Sengupta, Shiladitya Sengupta. IO125 is a potent inducer of tumor immunogenicity. [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 2231.
Abstract 2586: Evaluation of risk-based colposcopy in the ALTS trial
Authors: Angela H. Liu, Mark Schiffman, Julia C. Gage, Philip E. Castle, Nicolas Wentzensen
Journal: Cancer Research (2016)

Abstract Objective: Women referred to colposcopy have a wide spectrum of underlying risk of precancer that could influence colposcopic practice and management. We sought to evaluate important risk-strata based on HPV status, cytology, and colposcopic impression in women undergoing colposcopy. Methods: Among participants in the ASCUS-LSIL Triage Study, we stratified women from the immediate colposcopy and HPV triage study arms based on enrollment HPV typing, study cytology, and colposcopic impression. In each group, absolute risk of CIN3+ at enrollment colposcopy and cumulative risk over 2-year follow-up were estimated. Immediate CIN3+ risk of LSIL and HSIL cytology were used as thresholds for colposcopy referral and immediate treatment, respectively. Results: We observed substantial differences in risk of precancer across strata. Women with HSIL cytology, who were HPV16-positive, and high-grade colpscopic impression had a 71% baseline and 78% 2-year risk of CIN3+, respectively. HPV16-positive women with HSIL cytology and low-grade impression, and women with high-grade impression and either HSIL cytology or HPV16 infection, also showed significant CIN3+ risk exceeding the risk of HSIL. In contrast, women with normal colposcopy, &amp;lt;HSIL cytology, and absence of HPV16 infection had the lowest baseline CIN3+ risk (3.2%), below the colposcopy referral threshold in ALTS. Conclusion: Risk assessment at colposcopy can inform colposcopy-biopsy practice and guide management. In the low-risk group, biopsy yields little additional disease and a normal colposcopy may confer higher reassurance that CIN3+ is not present; while in the highest risk groups, immediate treatment without biopsy confirmation could be considered according to current guidelines. Analyses evaluating the benefit of multiple biopsies in these risk strata are underway and will be presented at the meeting. Citation Format: Angela H. Liu, Mark Schiffman, Julia C. Gage, Philip E. Castle, Nicolas Wentzensen. Evaluation of risk-based colposcopy in the ALTS trial. [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 2586.