tbuckley/cabot-search huggingface dataset:
660. Enhance Antitumor Effect by Combining Oncolytic Virus HF10 and Bevacizumab in the Treatment of Human Breast Cancer Xenograft
Authors: Gewen Tan, Hideki Kasuya, Zhiwen Wu, Tsutomu Fujii, Maki Tanaka, Saori Fukuda, Toyone Kikumori, Nengquan Sheng, Zhigang Wang, Yasuhiro Kodera
Journal: Molecular Therapy (2016)

Background: The high prevalence and poor prognosis of breast cancer provides a strong rationale for developing new treatment strategies. Oncolytic herpes simplex viruses has a promising prospect because of its selectivity, and the replicating and tumor killing ability. In our study, the antitumor effect by combining oncolytic virus HF10 and Bevacizumab in the treatment of human breast cancer xenograft is evaluated. Methods: The VEGFA gene transcription and protein expression were measured in candidate cell lines (MCF-7,T47D and MDA-MB-231) by RT-PCR, Western blot and ELISA. The MTT analysis was applied to evaluate the efficiency of the combination therapy in vitro. Viral replication was assessed by PCR and plaque assay. Animal models were formed by implanting MDA-MB-231 tumor in the flank site of female BALB/c nude mice. The HF10 group of advanced tumor model received two injections of 106 pfu/dose intratumorally on Day 1 and Day 14. The HF10 group of single tumor model received single injection of 106 pfu/dose intratumorally on Day 1. The Bevacizumab group received 5µg/g Bevacizumab intra-peritoneally twice a week for two weeks. The combination group received both intratumoral HF10 and intraperitoneal Bevacizumab at the same dose of single treatment groups. The tumor diameter was measured twice a week. On Day 3 and Day 36, the tumors were collected and observed respectively. Histopathological parameters were HIF1α, VEGFA, CD31 driven microvascular density, Caspase 3 and HSV-1 antigen. Results: MDA-MB-231 cells have the highest level of VEGFA expression, while T47D cells have the lowest level. The cytotoxic effect of HF10 is time- and dose- dependent in vitro. The combination therapy does not affect viral replication in vitro. The combination group has the smallest tumor volume comparing with other groups in both animal models (P<0.05). The combination therapy induces synergistic antitumor effect in both animal models. Viral distribution is significantly enhanced in the combination group compared to the HF10 group on both Day 3 and Day 36. Enhanced tumor hypoxia and the up-regulation of angiogenesis gene as well as enlarged population of apoptotic cells in the combination group are also demonstrated in the tumor sample on Day 3. Conclusions: Increased angiogenesis effect and limited viral distribution remain obstacles of oncolytic viral therapy. Anti-angiogenesis reagent is considered to be effective to achieve better antitumor effect of oncolytic virus. Our results show that Bevacizumab enhances viral distribution as well as tumor hypoxia and enlarges the population of apoptotic cells, and therefore induces a synergistic antitumor effect. It can be a promising virus-associated agent in the anticancer treatment.
Abstract A11: GIFT4-reprogrammed leukemic B cells for CLL immunotherapy.
Authors: Jiusheng Deng, Jonathon Cohen, Andrea Pennati, Yuanqiang Wu, Shala Yuan, Christopher Flowers, Jacques Galipeau
Journal: Clinical Cancer Research (2015)

Abstract Chronic lymphocytic leukemia (CLL) is characterized by the clonal proliferation and accumulation of typically CD5 positive B cells. Recently, we have developed a novel GM-CSF and IL-4 Fusion Transgene (named GIFT4), and found that GIFT4 protein triggers a robust anti-tumor B cell response (Deng et al. Cancer Research 2014). Considering CLL B cells broadly express the IL-4 receptor, we tested the immune function of human GIFT4 on CLL B cells, and discovered that GIFT4 protein possess a unique pharmaceutical property and reprograms leukemic B cells into anti-CLL effectors with T-helper features. We showed that GIFT4 protein led to hyper-phosphorylation of STAT5 in primary human CLL cells, which involed cluster of JAK1, JAK2 and JAK3 signaling. GIFT4 treated CLL B-cells up-regulated the expression of co-stimulatory molecules CD40, CD80 and CD86. Inhibition of JAK signaling with specific inhibitors suppressed the expression of the co-stimulatory molecules. GIFT4-reprogrammed CLL cells secreted IL-1β, IL-6, ICAM1 and substantial IL-2. GIFT4-CLL B cells further propelled the expansion of IFN-γ-producing autologous cytotoxic T cells and NK cells in vitro. Administration of GIFT4 protein in immune deficient NSG mice decreased the survival of primary CLL cells from patients in murine circulation. Altogether, our data demonstrate that GIFT4 has potent anti-CLL immune function by reprograming leukemic B cells into anti-CLL helper cells. We propose that the newly bio-engineered fusokine GIFT4 could serve as a potential therapeutic for CLL treatment, and GIFT4-reprogrammed leukemic B cells could provide an entirely novel B-cell driven therapeutic strategy for the potential personalized cellular immunotherapy for individuals with CLL. Citation Format: Jiusheng Deng, Jonathon Cohen, Andrea Pennati, Yuanqiang Wu, Shala Yuan, Christopher Flowers, Jacques Galipeau. GIFT4-reprogrammed leukemic B cells for CLL immunotherapy. [abstract]. In: Proceedings of the AACR Special Conference on Hematologic Malignancies: Translating Discoveries to Novel Therapies; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Clin Cancer Res 2015;21(17 Suppl):Abstract nr A11.
Outcomes of Allogeneic Stem Cell Transplant in Patients with Myeloid Leukemias Over 65 Years of Age. Rationale for Aggressive Therapy with Curative Intent.
Authors: Sergio Giralt, Rima M Saliba, Gabriela Rondon, Leandro de Padua Silva, Amin M. Alousi, Uday Popat, Marco De Lima, Borje Andersson, Partow Kebriae, Paolo Anderlini, Chitra Hosing, Roy Jones, Elizabeth J. Shpall, Richard E. Champlin, Issa F. Khouri
Journal: Blood (2008)
Effect of a costimulatory endodomain on the performance of T cells expressing CD19-directed chimeric antigen receptors (CARs) in subjects with relapsed/refractory B-cell malignancies
Authors: C. A. Ramos, B. Savoldo, E. Liu, C. M. Bollard, M. P. Mims, M. J. Keating, A. P. Gee, Z. Mei, C. M. Rooney, H. E. Heslop, M. K. Brenner, G. Dotti
Journal: Journal of Clinical Oncology (2011)

2541 Background: CARs usually combine the antigen binding domain of a monoclonal antibody with the ζ signaling domain of the T cell receptor complex. CAR expression in T cells produces potent MHC-unrestricted effector function against tumor cells in vitro but limited T-cell persistence in vivo, likely due to their incomplete activation, as tumors do not express costimulatory molecules. Incorporation of costimulatory endodomains in the CAR (e.g. CD28) may enhance their benefit in vivo. Methods: We report a phase I trial of T cells redirected to CD19 given to patients with refractory/relapsed B-cell malignancies. Subjects simultaneously received 2 autologous T-cell products, both expressing CARs with identical CD19-specific exodomains. In one product, the endodomain contained only the ζ sequence (CAR.19ζ) while the second incorporated a costimulatory CD28 domain (CAR.19-28ζ). We generated the T-cell products by activating autologous peripheral blood mononuclear cells with OKT3 followed by transduction with retroviral vectors encoding either CAR.19ζ or CAR.19-28ζ and ex vivo expansion for a median of 14 days (range 6-18) in the presence of IL-2. Six subjects have been treated at 3 cell dose levels (0.2, 1 and 2×108 cells/m2). Persistence of CAR+ T cells was assessed in blood by Q-PCR assays specific for each population. Results: All infusions were well tolerated. CAR.19-28ζ cells were detected at a low level after infusion, but progressively increased 7- to 63-fold, peaking at 1-2 wk, before declining to background levels over the ensuing 3 mo. By contrast, CAR.19ζ cells were barely detectable after infusion, showed no expansion and disappeared rapidly. Following treatment, 2 patients had stable disease for up to 6 mo and 4 had progressive disease. Conclusions: Infusion of both CAR.19ζ and CD19-28ζ T cells is safe at the doses used. Direct comparison of each cell product in individual patients showed that the CD28 endodomain enhances expansion and persistence of the CAR+ T cells. The limited clinical benefits suggest that additional modifications will be required and our approach will allow these changes to be systematically evaluated.
Effect of yoga on QOL, cortisol rhythym, and HRV for women with breast cancer undergoing radiotherapy.
Authors: L. Cohen, K. Chandwani, N. V. Raghuram, R. Haddad, G. H. Perkins, A. Spelman, R. Nagarathna, K. Johnson, A. Fortier, B. Arun, Q. Wei, C. Kirschbaum, H. R. Nagendra
Journal: Journal of Clinical Oncology (2011)

9009 Background: Radiotherapy (XRT) can decrease quality of life (QOL), disrupt cortisol rhythm and contribute to cardiovascular disease. We examined the effects of yoga on buffering changes in QOL, cortisol slope and heart rate variability (HRV) in women with breast cancer undergoing XRT. Methods: Patients with stage 0-III disease were recruited prior to XRT (baseline) and randomized to one of three groups: Yoga (YG-n=53) or Stretching (STR-n=56) 3 times a week for 6 weeks during XRT or Waitlist Control (WLC-n=54). Self-report measures of fatigue (BFI), depression (CESD), QOL (SF-36), benefit finding (BF), and spirituality (FACT-SP) were completed, and saliva and 10-minute ECGs were collected at baseline, end of treatment, and 1, 3, and 6 months later. We examined change from baseline for questionnaires and HRV data and slope analyses for cortisol. Results: By the end of XRT, the YG and STR groups had a reduction in fatigue while the WLC had an increase (YG: -0.23, STR: -0.45, WLC: 0.52; p’s<.05). At 1, 3, and 6 months after XRT, the YG group had a greater increase in SF-36 physical functioning compared to STR and WLC (1 month: 5.8, 2.0, 0.8; 3 months: 6.5, 3.4, -0.2; 6 months: 6.1, 3.4, 1.1; p’s<.05), with differences between STR and WLC at 3 months (p<.02) and similar outcomes for SF-36 general health scores. By 3 and 6 months after XRT, there was a significant increase in BF for the YG group (3 months: 3.1, -2.5, -2.5; 6 months: 1.1; -3.9; -4.7; p’s<.05). There were no differences for spirituality and depression. Cortisol slope was steepest for the YG group compared to STR and WLC (end of XRT: -0.12, -0.08, -0.08; 1 month: -0.12, -0.08, -0.07; p’s<.01). Within group changes of the standard deviation of all n-n intervals (SDNN) from baseline to the end of XRT revealed significant increases in HRV for YG (p<.05; 64.3ms) but not for STR or WLC (5.8ms, -8.1ms). Conclusions: While stretching improved fatigue and physical functioning, yoga buffered changes associated with XRT in terms of fatigue, QOL and benefit finding, resulted in steeper cortisol slopes, and increased HRV. This is the first yoga study to include an active control group, suggesting that the benefits of yoga are due to more than simple stretching, social support or other indirect effects.
Abstract 2013: SYNTHETIC LECTINS FOR THE DETERMINATION OF BREAST CANCER SUBTYPE
Authors: Kathleen M. O'Connell, Erin E. Gatrone, Anna A. Veldkamp, John J. Lavigne
Journal: Cancer Research (2015)

Abstract Glycans represent promising biomarkers for cancer diagnostics. Aberrant glycosylation is known to occur in cancer cells and changes continue to occur as the disease progresses. This study sought to determine if glycan ‘fingerprints’ can distinguish between differing cell types associated with cancer; specifically for the early detection and subtyping of breast cancers. Synthetic Lectins (SLs) are small peptides functionalized with boronic acids that selectively bind to glycans. Different SLs, with differing peptide backbones, acting as an array can be used to study glycans and generate glycan ‘fingerprints’ of analytes. An array of nine SLs, present on resin beads, were incubated with fluorescently labeled membrane proteins extracted from 1.) Breast cancer cell lines 2.) Matched normal and cancerous breast tissue from patients. Binding intensity information was obtained for each sample and analyzed statistically. Linear Discriminant Analysis was used to build two models, of breast cancer cell lines, based on a) metastatic potential and b) breast cancer subtype. Leave one out analysis determined that the models could distinguish between healthy/cancerous non-metastatic/cancerous metastatic cells with 98% accuracy and between breast cancer subtypes with 99% accuracy. Classification accuracy based on metastatic potential was validated using clinical specimens. N = 3 matched normal and cancerous tissues were analyzed and classification accuracies of 97% were obtained. We have developed an array, which distinguishes between healthy and cancerous cells as well as breast cancer subtypes with high accuracy. Work to expand validation to a larger group of patient samples as well as testing the array using patient serum is ongoing. Citation Format: Kathleen M. O'Connell, Erin E. Gatrone, Anna A. Veldkamp, John J. Lavigne. SYNTHETIC LECTINS FOR THE DETERMINATION OF BREAST CANCER SUBTYPE. [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 2013. doi:10.1158/1538-7445.AM2015-2013
Prenatal Carrier Screening
Authors: Imran S. Haque, Gabriel A. Lazarin, Ronald J. Wapner
Journal: JAMA (2016)

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Assessing the Predictive Value of Plasma FLT3-L Levels for Hematologic Toxicity after Yttrium-90 Ibritumomab Tiuxetan ([90Y]-Zevalin) Given as Consolidation in Patients with Advanced B-Cell Follicular NHL Responding to First Line Therapy.
Authors: F. Morschhauser, J. Radford, A. van Hoof, I. Kuss, A. Chlistalla, A. Hagenbeek
Journal: Blood (2005)
Prospective study of cognitive function (cog fcn) in women with early-stage breast cancer (ESBC): Predictors of cognitive decline.
Authors: Hope S. Rugo, Amy N DeLuca, Lara Heflin, Sally Fang, Michelle E. Melisko, Mark M. Moasser, John W. Park, Amy Jo Chien, Pamela N. Munster, Laura Esserman, Susan M Landau, William J Jagust, Joel H Kramer
Journal: Journal of Clinical Oncology (2013)

6620 Background: Cog complaints are common among women receiving adjuvant therapy (Rx) for ESBC. Longitudinal prospective data is needed to help identify predictors of cog decline. We conducted a prospective trial to evaluate the effects of chemo- (CTX) &amp; hormone therapy (HRx) on brain &amp; cog fcn in pts with ESBC using multiple objective &amp; subjective tests as well as MRI/PET imaging. Here we report evaluation of clinical characteristics that predict decline in cog fcn. Methods: Eligibility included female patients (pts) planning to receive adjuvant Rx for ESBC. Pts were enrolled in 3 Rx groups (grps): CTX, CTX &amp; HRx, and HRx, with a 4 th no Rx age/education matched control grp. All pts underwent a battery of objective &amp; subjective cog tests before start of Rx, 1 mo after CTX or 5 mo after start of HRx (FU1), then 9 mo (FU2) &amp; 18 mo (FU3) after CTX. Brain MRI, PET &amp; serum estradiol (E) were performed at baseline, FU1 &amp; FU2. Results: 81 pts were enrolled as follows, 14 CTX, 33 CTX &amp; HRx, 22 HRx, 12 control. 90% completed FU1, 72% FU2, &amp; 62% FU3, with 29 pts waiting to complete testing. Demographics were similar between grps, median age 54, 78% Caucasian. At each FU, ~25% of pts showed decline in cog fcn compared to the prior time point using a reliable change index; 51% showed decline at &gt; 1 time point, primarily in tests measuring executive function &amp; verbal memory. 62% of pts who declined from baseline to FU1 later stabilized or improved; 77% of pts who declined from FU1 to FU2 later stabilized or improved. Compared to controls, receipt of CTX &amp; HRx (OR 3.15, p=.008), or HRx overall (OR 4.94, p=.004) but not serum E, menopausal status, or CTX, were significant predictors of decline at any time point. Rx group did not predict poorer perceived cog fcn (FACT-COG); depression &amp; fatigue did not predict decline in objective cog fcn. Conclusions: Decline in cog fcn is common in pts receiving adjuvant Rx for ESBC. Predictors included CTX &amp; HRx, or HRx overall but not other treatment &amp; pt related factors. Ongoing HRx, particularly after CTX, appears to be a risk factor for worse cog fcn. Pts should be aware that HRx may be a risk factor for cog deficits, &amp; intervention studies should be designed to focus on this group of pts. Funding: NIH R01 1AG025303-01A2. Clinical trial information: NCT00755313.
Non-Myeloablative Conditioning with Allogeneic Progenitor Cell Transplantation for Relapsed Hodgkin’s Lymphoma: High Response Rate Despite Prior Chemoresistance.
Authors: Steven C. Goldstein, Selina M. Luger, Edward Stadtmauer, Stephen Schuster, Donald Tsai, Sunita Nasta, Alison Loren, Alexander Perl, Greg Orloff, Julie Oliver, Robert Sachs, Stephen Emerson, David L. Porter
Journal: Blood (2004)
IDH1 and IDH2 Mutations in Therapy-Related Acute Myeloid Leukemia Are Associated with a Normal Karyotype or Der(1;7)(q10;p10) Combined with RUNX1 Mutations,
Authors: Maj K. Westman, Morten T. Andersen, Jens Pedersen-Bjergaard, Mette K. Andersen
Journal: Blood (2011)
Brentuximab Vedotin in Combination with Multi-Agent Chemotherapy Is Well Tolerated and Shows Promising Activity As Frontline Treatment for Primary Mediastinal B-Cell Lymphoma
Authors: Jakub Svoboda, Lauren E. Strelec, Sunita Dwivedy Nasta, Daniel J. Landsburg, Anthony R. Mato, Barbara Pro, Stefan Klaus Barta, Nirav N. Shah, Sarah Jordan Nagle, Elise A. Chong, Ellen Napier, Samantha Garrett, Stephen J. Schuster
Journal: Blood (2015)
Treatment Experience of Acute Lymphoblastic Leukemia with Hgm/LAL07 Regimen at Hospital General De Mexico
Authors: Christian Omar Ramos Peñafiel, Humberto Baldemar Castellanos Sinco, Efreen Montaño Figueroa, María Guadalupe Leon Gonzalez, Etta Rozen Fuller, Juan Julio Kassack Ipiña, Carlos Martinez Murillo, Juan Collazo Jaloma
Journal: Blood (2015)
Phase II Pilot Study of Rituximab + CHOP in Patients with Newly Diagnosed Waldenström’s Macroglobulinemia, an Eastren Cooperative Oncology Group Trial (Study E1A02).
Authors: Rafat Abonour, Lijun A. Zhang, Vincent Rajkumar, Gordan Srkalovic, Philip R. Greipp, Rafael Fonseca, Morie Gertz
Journal: Blood (2007)
Usefulness of Wharton’s Jelly, Cord Blood, and Adipose Tissue as Alternative Sources of Mesenchymal Stem Cells.
Authors: Jun Ho Jang, Hyun Woo Lee, Young-Woo Eom, Seok Yun Kang, Joon Seong Park, Jin Hyuk Choi, Hugh C. Kim
Journal: Blood (2006)
B-Cell Lymphoproliferative Disorders with t(11;14)(q13;q32) or t(14;18)(q32;q21) Can Be Subdivided into 4 Distinct Categories Based on Their Pattern of Additional Cytogenetic Aberrations and Antigen Expression.
Authors: Claudia Haferlach, Lena Reindl, Frank Dicker, Susanne Schnittger, Torsten Haferlach, Wolfgang Kern
Journal: Blood (2007)
Abstract 2751: Identification of predisposition genes involved in thyroid and breast carcinomas in patients with family history of these tumors by whole exome sequencing
Authors: Maisa Pinheiro, Fabio Marchi, Sandra Drigo, Patricia Reis, Luiz Lehmann Coutinho, Sonia Andrade, Luis Paulo Kowaslki, Maria Isabel Achatz, Silvia Rogatto
Journal: Cancer Research (2015)

Abstract A significant number of patients with family history of breast (BC) and papillary thyroid carcinomas (PTC) have been detected at Oncogenetics Dept of AC Camargo Cancer Center, SP, Brazil. The aim of this study was to identify genetic alterations in patients with family cancer history of BC and TC by using whole exome sequencing (WES) analysis. All patients included in this study fulfilled the inclusion criteria as follows: proband with non-medullary TC and/or BC with family cancer history of these tumors AND at least two 1st- or 2nd- degree relatives with one of these tumors either diagnosed &amp;lt;45 years old OR one 1st- relative with one of these tumors and proband diagnosed &amp;lt;40 years old AND history of other tumors. Exclusion criteria comprised female patients with BC treated by radiotherapy before TC diagnosis and probands affected with common mutations in major hereditary predisposition genes. Twenty-four blood samples and four tumor samples were included in WES analysis. Libraries were prepared by using Nextera Exome Enrichment kit following manufacturer's instructions and were sequenced in HiSeq2000 sequencer (Illumina). An average depth of 95x was obtained. The analysis focusing in single nucleotide polymophisms (SNPs) in high penetrance genes detected 12 SNPs in six genes. Particularly, two potential pathogenic SNPs mapped at BRCA1 gene, previously associated with PTC and BC, were detected in at least 25% of samples. The evaluation of rare pathogenic alterations shared by all cases revealed two single nucleotide variations (SNVs) mapped at HYDIN gene. Alternative variants of HYDIN gene were previously detected in serum of patients diagnosed with colorectal, lung, breast and thyroid tumors [Laske K et al, Cancer Immunol Res 1: 190, 2013]. Further analyses are needed to confirm these alterations as potential predisposition candidates associated with breast and thyroid hereditary carcinomas. Furthermore, the data generated in this study could be incorporated into the general knowledge of cancer genetics, allowing the development of prevention strategies, screening and genetic counseling in these families. Financial Support: FAPESP (2013/01867-8 and 2014/03983-8) and CNPq (481132/2012-0) Citation Format: Maisa Pinheiro, Fabio Marchi, Sandra Drigo, Patricia Reis, Luiz Lehmann Coutinho, Sonia Andrade, Luis Paulo Kowaslki, Maria Isabel Achatz, Silvia Rogatto. Identification of predisposition genes involved in thyroid and breast carcinomas in patients with family history of these tumors by whole exome sequencing. [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 2751. doi:10.1158/1538-7445.AM2015-2751
Monitoring and Preventing Congenital Zika Syndrome
Authors: Margaret A. Honein, Denise J. Jamieson
Journal: New England Journal of Medicine (2016)

The devastating fetal and infant outcomes associated with thalidomide use and rubella infection during pregnancy were key factors in the establishment of population-based surveillance for birth defects in the United States and globally to better monitor and address the effect of teratogens.1,2 This year, the recognition that Zika virus (ZIKV) infection during pregnancy can cause microcephaly and serious brain abnormalities and growing evidence of its association with other birth defects has similar potential to transform our approach to global surveillance for, research on, and prevention of birth defects.3 ZIKV infection during pregnancy highlights the challenges of adequately monitoring and . . .