tbuckley/cabot-search huggingface dataset:
Abstract 867: Reproductive factors and risk of B-cell non-Hodgkin lymphoma among women in Los Angeles
Authors: Yani Lu, Jianning Luo, Sophia Wang, Jane Sullivan-Halley, Wendy Cozen, Leslie Bernstein
Journal: Cancer Research (2015)

Abstract Background: Overall, non-Hodgkin lymphoma (NHL) incidence is higher in men than women, and the male to female ratio differs by NHL subtype. Historically, female reproductive characteristics and patterns have been inconsistently linked to NHL risk, though studies on this topic remain limited. Because a woman experiences changes in immune function during pregnancy, that permit her to establish and maintain a successful pregnancy, we hypothesize that such pregnancy-associated changes in immune function could affect the risk of NHL, a cancer of the immune cells. Methods: We conducted a population-based case-control study among women in Los Angeles County comprising 998 histologically confirmed B-cell NHL patients diagnosed 2004-2008 from the Los Angeles Cancer Surveillance Program and 998 individually matched controls (matched on age, race and socioeconomic status). Conditional logistic regression was used to calculate the associations [odds ratios (OR) and 95% confidence intervals (CI)] between female reproductive factors (e.g., ever pregnant; number of full-term pregnancies; breastfeeding) with B-cell NHL overall and unconditional logistic regression was used to calculate the associations with major NHL subtypes. Results: Compared to women who had never been pregnant, women who had full-term pregnancies had 17% decreased risk of B-cell NHL (OR = 0.83, 95% CI = 0.64-1.08); the decreased risk was most pronounced for the diffuse large B-cell lymphoma (DLBCL) subtype (OR = 0.68, 95% CI = 0.47-0.98). Increasing number of full-term pregnancies was inversely associated with B-cell NHL overall (P-trend = 0.02), DLBCL (P-trend = 0.03) and follicular lymphoma (P-trend = 0.04). Women who had reported breastfeeding also had decreased risk of B-cell NHL overall (OR = 0.80, 95% CI = 0.64-1.00) and follicular lymphoma (OR = 0.71, 95% CI = 0.50-1.00). Among women who had full-term pregnancies, women who breastfed for 60 weeks or more had 30% decreased risk of B-cell NHL overall (OR = 0.70, 95% CI = 0.52-0.93; P-trend = 0.06), which was consistent for follicular lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). Conclusions: Our results provide evidence for an association between female reproductive factors and decreased risk of B-cell NHL, supporting a role for hormonal factors in B-cell NHL etiology. Citation Format: Yani Lu, Jianning Luo, Sophia Wang, Jane Sullivan-Halley, Wendy Cozen, Leslie Bernstein. Reproductive factors and risk of B-cell non-Hodgkin lymphoma among women in Los Angeles. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 867. doi:10.1158/1538-7445.AM2015-867
Regulation of Stimulated and Basal Release of Weibel-Palade Bodies By Syntaxin-3 Containing SNARE-Complexes
Authors: Dorothee Van Breevoort, Maryam Wahedi, Maaike Schillemans, Tom Carter, Stephan Huveneers, Maartje van den Biggelaar, J.J. Voorberg, Ruben Bierings
Journal: Blood (2014)
Choosing the Right Patients for Clinical Trials in Essential Thrombocythemia or Polycythemia Vera: Leukemic or Fibrotic Transformation Risk Assessment among 1061 Patients from a Single Institution.
Authors: Ayalew Tefferi, Naseema Gangat, Alexandra P. Wolanskyj, Susan M. Schwager, Animesh Pardanani, Ruben A. Mesa, Rebecca F. McClure, Chin-Yang Li, Curtis A. Hanson
Journal: Blood (2007)
Abstract 1957: Negative regulation of Sox9 by glycogen synthase kinase 3 beta phosphorylation and SCFFbw7-dependent ubiquitination in cancer
Authors: Xuehui Hong, Wenyu Liu, Hiroyuki Inuzuka, Lianxin Liu, Sharon R. Pine
Journal: Cancer Research (2015)

Abstract Sox9 is a member of the SOX [Sry-related high-mobility group (HMG) box] family of transcription factors, with known functions in proliferation, epithelial-mesenchymal transition (EMT), stem cell maintenance and senescence. Sox9 protein levels are elevated in several different cancer types, including lung cancer and osteosarcoma. Furthermore, Sox9 overexpression is associated with poor survival in both cancer types. We recently reported that Sox9 is a direct transcriptional target of the Notch signaling pathway and mediates Notch1-induced EMT in lung cancer (Capaccione et al., Oncotarget, 2014). Fbxw7 (F-box and WD repeat domain-containing 7) is a member of the SCFFbw7E3 ubiquitin ligase complexthat targets several oncogenic proteins for degradation, including Notch1. We hypothesized that Sox9 is targeted for degradation by SCFFbw7. Knocking down or overexpressingFbxw7 significantly increasedor decreased, respectively, endogenous Sox9 protein levels in lung cancer and osteosarcoma cell lines. In addition, overexpression of Fbxw7 resulted in active degradation of ectopic Sox9 protein levels, when assessed in combination with cycloheximide, and did so in a dose dependent-manner.Furthermore, both Sox9 and FBXW7 were detected in immunoblots after the reciprocal protein was immunoprecipitated. Because substrate degradation by SCFFbw7 is typically phosphorylation-dependent, frequently by glycogen synthase kinase (GSK)3-beta, we examined whether modulation of GSK3-beta could affect FBXW7-induced Sox9 degradation. Treatment of cells with the GSK3-beta inhibitor, CHIR99021, completely abolished Sox9 degradation by ectopically overexpressed FBXW7, in a dose-dependent manner. We next identified four putative phosphorylation sites within potential FBXW7 degron motifs in Sox9.Mass spectrophotometric analysis confirmed these sites within Sox9 are indeed phosphorylated.In summary, we found that the E3 ubiquitin ligase complex (SCFFbw7) targets Sox9 for ubiquitin-mediated degradation in a GSK3-beta-mediated Sox9 phosphorylation-dependent manner. As a result, this negative regulation of Sox9 by GSK3-beta/FBXW7 could lead to inhibition of Sox9-mediated proliferation, EMT and stemness. This new regulatory mechanism of Sox9 could have diagnostic and therapeutic implications for lung cancer, osteosarcoma, as well as other cancers. Citation Format: Xuehui Hong, Wenyu Liu, Hiroyuki Inuzuka, Lianxin Liu, Sharon R. Pine. Negative regulation of Sox9 by glycogen synthase kinase 3 beta phosphorylation and SCFFbw7-dependent ubiquitination in cancer. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1957. doi:10.1158/1538-7445.AM2015-1957
284. High-Efficiency Targeted Introduction of an Anti-CD19 CAR Into the CCR5 Locus in Primary Human T Cells
Authors: Malika Hale, Guillermo S. Romano Ibarra, Iram F. Khan, Jaya Sahni, Andrew M. Scharenberg, David J. Rawlings
Journal: Molecular Therapy (2015)

The safety and efficacy of anti-CD19 chimeric antigen receptor (CD19-CAR) therapeutic cell transfer for treatment of CD19+ B cell malignancies is currently being evaluated in multiple clinical trials. Current protocols employ randomly integrating lentiviral or gamma-retroviral vectors to introduce the CAR into patient- or donor-derived T cells. This strategy carries with it an inherent risk of insertional mutagenesis as well as variable CAR expression. Here we have developed a method of targeting a CD19-CAR construct directly into the CCR5 locus by homology directed recombination (HDR). Using a CCR5 megaTAL nuclease (an engineered homing endonuclease and TALEN chimera) and an AAV donor template (comprised of an MND promoter-CD19CAR-T2A-BFP expression cassette between CCR5 homology arms), we obtained efficient targeting rates in primary human T cells. CAR expression was confirmed by flow cytometry and homologous recombination within the CCR5 locus was verified by PCR analysis and by direct sequencing. Rates of biallelic HDR were assessed using single cell PCR. T cells with the CD19-CAR at the CCR5 locus demonstrated activation, cytokine production and specific killing in the presence of CD19+ cells. Activity levels were indistinguishable from T cells transduced with LV expressing an identical CD19-CAR construct. Seamless targeting to CCR5 has important therapeutic advantages over traditional viral delivery, including a reduced potential for oncogenic insertions and uniform levels of gene expression, in parallel with effective disruption of the co-receptor for CCR5-tropic HIV-1. Further, the targeting methods used are directly amenable to clinical application. As HIV patients develop aggressive B cell lymphomas at increased rates, we believe this technique has substantial potential for clinical implementation including the protection of autologous CD19-CAR effector T cell products from HIV infection in vivo.
Genome-Wide Analysis of Copy Number Analysis of Myelodysplastic Syndromes Using High-Density SNP-Genotyping Microarrays.
Authors: Masashi Sanada, Yasuhito Nannya, Kumi Nakazaki, Go Yamamoto, Lili Wang, Noriko Hosoya, Akira Hangaishi, Mineo Kurokawa, Shigeru Chiba, Seishi Ogawa
Journal: Blood (2005)
The Efficacy and Toxicity of the RAD Regimen (Revlimid®, Adriamycin®, Dexamethasone) in Relapsed and Refractory Multiple Myeloma - A Phase I/II Trial of “Deutsche Studiengruppe Multiples Myelom”.
Authors: Stefan Knop, Christian Gerecke, Peter Liebisch, Max S. Topp, Georg Hess, Uwe Platzbecker, Sandra Frohnert, Hermann Einsele, Ralf Bargou
Journal: Blood (2007)
N-acetylcysteine in preclinical mouse and baboon models of thrombotic thrombocytopenic purpura
Authors: Claudia Tersteeg, Jan Roodt, Walter J. Van Rensburg, Charlotte Dekimpe, Nele Vandeputte, Inge Pareyn, Aline Vandenbulcke, Barbara Plaimauer, Seb Lamprecht, Hans Deckmyn, José A. Lopez, Simon F. De Meyer, Karen Vanhoorelbeke
Journal: Blood (2016)
Engineered Oncogene Activation by Somatic Hypermutation Results in a Faithful Mouse Model of MGUS/Multiple Myeloma.
Authors: Davide F. Robbiani, Kaity Colon, Paul Szabo, Maurizio Affer, Helen Nickerson, Chen-Feng Qi, Herbert C. Morse, Marta Chesi, Peter Leif Bergsagel
Journal: Blood (2004)
48. Treatment of Methylmalonic Acidemia by Promoterless Gene-Targeting Using Adeno-Associated Viral (AAV) Mediated Homologous Recombination
Authors: Randy J. Chandler, Adi Barzel, Mark A. Kay, Charles P. Venditti
Journal: Molecular Therapy (2016)

Methylmalonic acidemia (MMA) is an autosomal recessive inborn error of metabolism most typically caused by mutations in methylmalonyl-CoA mutase (MUT). While the hallmark of this disease is elevated levels of methylmalonic acid in the plasma, other disease related metabolites such as methylcitrate are elevated in the plasma as well. Patients with MMA suffer from frequent and potential lethal bouts of metabolic instability that can be eliminated by liver transplantation. Adeno-associated viral (AAV) gene therapy has shown great promise as the treatment for MMA in a murine model of the disease. However, a majority of the AAV-treated mice developed hepatocellular cancer, which was determined to arise from AAV-mediated insertional mutagenesis. In an attempt to create a safer gene therapy platform for the treatment of MMA, we created a novel vector for site-specific gene addition of human MUT into the mouse albumin (Alb) locus. This promoterless AAV vector contains a 2A-peptide coding sequence proximal to a codon-optimized human MUT gene. The 2A-MUT sequence is flanked by arms of homology immediately upstream of mouse Alb stop codon. Since albumin is expressed exclusively in hepatocytes, we prepared an AAV serotype 8 vector to take advantage of the murine liver tropism conferred by this capsid. This newly created vector was named AAV8-Alb-A2-MUT. After site-specific integration of the vector into the Alb locus in the liver, ribosomal skipping generates both Alb and MUT as separate proteins derived from the same transcript. We delivered a dose of 2.5e12 GC of AAV8-Alb-2A-MUT to five mice with MMA by intraperitoneal injection at birth. At one month post-injection, we observed increased hepatic expression of the MUT by western blot, improved growth and a significant reduction of disease related metabolites, in the treated MMA mice (Table 1). This gene delivery approach is anticipated to provide permanent hepatic transgene expression while reducing the risk of off-target integration and vector-mediated insertional mutagenesis.Table 1Markers of Correction in MMA Murine ModelUntreated (n=3-8)AAV8-Alb-A2-MUT (n=5)P ValuePercent of Wild-type Mut ExpressionND11.3+/-9.1NAPlasma Methylmalonic Acid (uM)969+/−396563+/−98<0.05Plasma Methylcitrate (nM)5, 020+/−8732, 904+/−638<0.0001Weight at 1 Month6.9+/−1.610.7+/−0.6<0.003 Open table in a new tab
Efficacy of infusional 5-fluorouracil, doxorubicin, and mitomycin-C (iFAM) chemotherapy and analysis of prognostic factors in previously treated advanced hepatocellular carcinoma.
Authors: Kyu-Hyoung Lim, Sae-Won Han, Do-Youn Oh, Seock-Ah Im, Tae-You Kim, Yung-Jue Bang
Journal: Journal of Clinical Oncology (2012)

269 Background: In advanced HCC, the role of salvage chemotherapy after failure of prior chemotherapy including sorafenib has not been fully studied. The aims of this study were to evaluate the efficacy of infusional 5-fluorouracil (5-FU), doxorubicin, and mitomycin-C (iFAM) as salvage regimen in advanced HCC and to identify the prognostic factors in a salvage setting. Methods: Eligibility included the following: 1) age &gt; 18 years; 2) Diagnosed as HCC; 3) previously treated with palliative chemotherapy; 4) ECOG PS 0-2; 5) Child-Pough Class A or B; and 6) adequate BM and renal function. iFAM consisted of 5-FU 800 mg/m2 over 10 hours on days 1-5, doxorubicin 30 mg/m2 on day 1 and mitomycin-C 8 mg/m2 on day 1, every 4 weeks. Response evaluation was done every 8 weeks with RECIST criteria. Results: A total of thirty-five patients were enrolled. The median age was 50.2 years (range: 23.3-74.7). ECOG PS was; PS 0-1 (80%) and PS 2 (20%). The etiology of HCC was; HBV (82.8%), HCV (2.9%) and others (14.3%). Liver function was; Child Pough A (91.4%) and B (8.6%). Nine patients had macrovascular invasion and all had extrahepatic metastatic lesion. Prior chemotherapies were sorafenib or 5-FU based regimens. A total of 94 cycles of iFAM were delivered (median 2: range 1-7). There were 2 PR and 6 SD, resulting in RR 5.7% (95% CI, 1.6-18.6%) and DCR 22.9% (95% CI, 12.1-39%). The PFS and OS were 2.4 months and 8.6 months, respectively. The 6- and 12-month survival rates were 67.7% and 35.3%, respectively. Grade 3/4 hematologic toxicity was neutropenia (14.3%). Frequent non-hematological toxicities were; anorexia (45.7%), alopecia (40%), stomatitis (20%), all of which were grade 1/2. In multivariate analysis, PS and serum α-FP were significantly associated with OS. Patients were classified into 3 risk groups based on the number of prognostic factors (0 vs. 1 vs. 2). This classification was well-correlated to OS (16.1 months vs. 10.5 months vs. 3.8 months, respectively; p &lt; 0.0001). Conclusions: iFAM is an effective and tolerable treatment option in advanced HCC and could be considered as salvage regimen. PS and α-FP are significant prognostic factors in a salvage setting.
Targeting Chk1 in p53-deficient triple-negative breast cancer is therapeutically beneficial in human-in-mouse tumor models
Authors: Cynthia X. Ma, Shirong Cai, Shunqiang Li, Christine E. Ryan, Zhanfang Guo, W. Timothy Schaiff, Li Lin, Jeremy Hoog, Reece J. Goiffon, Aleix Prat, Rebecca L. Aft, Matthew J. Ellis, Helen Piwnica-Worms
Journal: Journal of Clinical Investigation (2012)

shown that inhibition of Chk1 in a p53-deficient background results in apoptosis in response to DNA damage.
Novel Dissemination Efforts for Hematology-Related Serious Adverse Drug Reactions (sADRs): Findings from the Research on Adverse Drug Events and Reports Project (RADAR)
Authors: Cara C Tigue, Dennis P West, Dennis W Raisch, Beatrice J Edwards, Simone N Boyle, Athena T Samaras, Paul Bennett, Charles L. Bennett
Journal: Blood (2008)
Treatment of metastatic renal cancer with high-dose interleukin-2 after targeted therapy.
Authors: Robert E. Hawkins, Victoria Galvis, Jonathan Shanks, Neha Dalal, Fiona Thistlethwaite, Andrea Spencer-Shaw
Journal: Journal of Clinical Oncology (2012)

439 Background: High-Dose Interleukin-2 (HD IL2) remains a good option for treatment of metastatic renal cancer. As a first-line treatment, in carefully selected patients, it can produce high rates of response ( OR 50%; CR 25%) (Shablak A et al., J Immunotherapy 2011, 34(1):107-122). Its use after targeted therapies is controversial and there are reports of increased toxicity, particularly an increased incidence of cardiovascular toxicity (and possibly a reduced response rate (Cho DC et al., J Immunotherapy 2009, 32(2):181-520). However, there is potential to use it either in patients who have failed treatment with targeted therapy or as a consolidation therapy after successful treatment with a targeted agent. Methods: Here we present the outcomes of 16 patients treated with first-line immunotherapy with HD-IL2 after targeted therapy: of these 8 had been treated after failure of 1-3 lines of targeted therapy and 8 have been treated as consolidation after initial response to sunitinib. The histological characteristics of the tumours all fitted into the “favourable” group as defined previously by us and all had high levels of expression of CAIX (&gt; 80%). All had ECOG PS 0/1, a satisfactory baseline stress echo, an interval of at least 8 weeks from last dose of targeted agent to start of HD-IL2 and at most 2 organs of disease. Results: Toxicity is indistinguishable from that of patients without prior treatment and no patient needed inotropic support or admission to intensive care. The number of doses given per cycle was also similar to that in unpretreated patients. Overall the response rates are excellent – with 9/13 evaluable patients having RECIST defined response and 6/13 having a complete remission. To date none of the patients in complete remission have realpsed but follow up is relatively short with the longest being 24 months. The responses have been particularly striking following treatment with mTor inhibitors. Conclusions: Overall, HD IL2 can be given safely in carefully selected patients after targeted therapies. It appears to be effective as a salvage therapy and potentially as a consolidation therapy. Updated results will be presented.
C22orf2 Gene (22q13.1) Translocation Downstream of Bcr Breakpoint (22q11) to the Derivative 9 Chromosome Is Associated with Reduced Expression of Its Protein, the Beta-Catenin Antagonist Chibby, in Chronic Myeloid Leukemia Progenitors
Authors: Michela Aluigi, Manuela Mancini, Elisa Leo, Fausto Castagnetti, Carmen Baldazzi, Enza Barbieri, Maria Alessandra Santucci
Journal: Blood (2011)
Abstract 3728: Rapid deployment of statewide tobacco cessation program for cancer patients
Authors: Laura Petersen, Hilary Baca, Karen Brown, Jamie Lindsay, Sarah Mott, Jane Severson, Anna Schulze, Graham Warren
Journal: Cancer Research (2015)

Abstract Purpose Tobacco use is not only associated with the development of cancer, but after a patient develops cancer, its continued use is associated with poorer cancer treatment outcomes. Despite this fact, most oncologists do not regularly provide tobacco cessation support. The purpose of this study was to implement an expedited process of patient identification and tobacco cessation for cancer patients. Methods The Michigan Oncology Quality Consortium (MOQC) collaborated with the Michigan Department of Community Health, Blue Cross and Blue Shield of Michigan, and the Michigan Cancer Consortium to enhance tobacco cessation support for cancer patients. A statewide tobacco cessation demonstration project using a lean engineering approach was developed to provide structured tobacco assessments, referral to state quitline resources, and provide tailored cessation support to cancer patients consisting of behavioral counseling and free pharmacotherapy where appropriate. These steps were rapidly deployed in over 30 locations including those in private oncology practices and cancer centers in the first year. Data were analyzed to evaluate participation, retention, and quit rates for cancer patients enrolled in the program. Results Previous reports have described high rates of patient contact and participation in the cessation program. In the 690 patients with at least 12 months since program enrollment, 200 (29%) participated in only 1 call, 313 (45%) participated in 1-2 follow-up calls, and 177 (26%) participated in 3 or more follow-up calls. Follow-up 30 day quit rate data was obtained in 198, 138, and 199 patients at 3, 6, and 12 months respectively. Self-reported quit rates remained largely consistent with 29.8% at 3 months, 27.5% at 6 months, and 30.2% at 12 months. Conclusions The MOQC demonstration project represents a model partnership between payors, clinicians, and statewide quitlines that maintained consistent and moderate quit rates in cancer patients. Large-scale deployment of this model program may provide a clinically efficient and effective mechanism to enhance widespread tobacco cessation efforts for cancer patients. Citation Format: Laura Petersen, Hilary Baca, Karen Brown, Jamie Lindsay, Sarah Mott, Jane Severson, Anna Schulze, Graham Warren. Rapid deployment of statewide tobacco cessation program for cancer patients. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3728. doi:10.1158/1538-7445.AM2015-3728
Pleural Effusion in Patients (pts) with Chronic Myelogenous Leukemia (CML) Treated with Dasatinib after Imatinib Failure.
Authors: Alfonso Quintas-Cardama, Hagop M. Kantarjian, Reginald Munden, Moshe Talpaz, John Bruzzi, Susan O’Brien, Guillermo Garcia-Manero, Claude Nicaise, Jorge Cortes
Journal: Blood (2006)
Correction
Authors: Qiang Pan-Hammarström, Aleksi Lähdesmäki, Yaofeng Zhao, Likun Du, Zhihui Zhao, Sicheng Wen, Victor L. Ruiz-Perez, Deborah K. Dunn-Walters, Judith A. Goodship, Lennart Hammarström
Journal: The Journal of Experimental Medicine (2006)
Improved Remission Induction Rate of Childhood AML: Preliminary Results of the AML02 Trial.
Authors: Jeffrey Rubnitz, Bassem Razzouk, Paul Bowman, Gary Dahl, Norman Lacayo, Jeffrey Taub, Yaddanapudi Ravindranath, Soheil Meshinchi, Gladstone Airewele, Shelly Lensing, Stanley Pounds, Raul Ribeiro, Ching-Hon Pui, Elaine Coustan-Smith, Dario Campana
Journal: Blood (2005)
Discovery and Preclinical Characterization of INCB018424, a Selective JAK2 Inhibitor for the Treatment of Myeloproliferative Disorders.
Authors: Jordan Fridman, Roberto Nussenzveig, Phillip Liu, James Rodgers, Timothy Burn, Patrick Haley, Peggy Scherle, Robert Newton, Gregory Hollis, Steven Friedman, Srdan Verstovsek, Kris Vaddi
Journal: Blood (2007)