tbuckley/cabot-search huggingface dataset:
Excessive Neurotoxicity in a Phase II Trial of Combined Bortezomib and Rituximab in Patients with Relapsed/Refractory Mantle Cell (MCL) and Follicular (FL) Non-Hodgkin’s Lymphoma.
Authors: Kristie A. Blum, Margaret S. Lucas, Jeffrey S. Johnston, James Dalton, Donn Young, Robert A. Baiocchi, Thomas S. Lin, Pierluigi Porcu, John C. Byrd
Journal: Blood (2006)
Day 21 Chimerism Is a Critical Prognostic Factor for Graft Failure and Survival in Recipients of Myeloablative Conditioning and Umbilical Cord Blood (UCB) Transplantation
Authors: Nelli Bejanyan, Claudio G Brunstein, Qing Cao, Bharat Thyagarajan, Karamjeet S. Sandhu, Mukta Arora, Daniel J. Weisdorf, John E Wagner
Journal: Blood (2014)
Abstract 3399: Using protein chips to develop a highly specific HER2 antibody for HER2 amplification testing
Authors: Lixin Zhou, Kehu Yuan, Fangfang Ren, Lili Qi, Zhongwu Li, Guiyin Wu, Xiaozheng Huang, Yi Shen, Min Zhao, Wei Fu, Huibo Liu, Boyang Chu, Guangli Wang, Youmin Shu, Donghui Ma, Wei-Wu He, Jian Chen
Journal: Cancer Research (2015)

Abstract Human epidermal growth factor receptor 2 (HER2) is an orphan receptor tyrosine kinase member of the EGFR families and is found to be a key tumor driver gene. In breast cancer and gastric cancer, HER2 amplification can be effectively treated by its neutralizing antibody, trastuzumab. In clinic, the HER2 immunohistochemistry (IHC) was used as the primary screening method to diagnose HER2 amplification. However, recent evidence suggested that the frequently used rabbit HER2 antibody 4B5 cross reacted to another family member HER4. IHC staining also indicated that it has strong non-specific cytoplasmic and nucleus staining in normal gastric mucosal cells and some gastric cancer samples. Using a protein lysate array which covers 85% of the human proteome, we have successfully identified and confirmed that the 4B5 bound to HER4 and a nuclear protein ZSCAN18 besides HER2. The non-specific binding accounts for the unexpected cytoplasmic and unclear staining of 4B5 on normal gastric epithelium. Finally, we have developed a novel HER2 mouse monoclonal antibody UMAB36 with similar sensitivity to 4B5 but only reacted to HER2 across the 17,000 proteins on the protein chip. In 129 breast cancer and 158 gastric cancer samples, UMAB36 showed 100% sensitivity and specificity comparing to the HER2 FISH reference results with no unspecific staining in the gastric mucosa layer. UMAB36 could provide an alternative high specific IHC reagent for HER2 amplification testing in gastric cancer population. Citation Format: Lixin Zhou, Kehu Yuan, Fangfang Ren, Lili Qi, Zhongwu Li, Guiyin Wu, Xiaozheng Huang, Yi Shen, Min Zhao, Wei Fu, Huibo Liu, Boyang Chu, Guangli Wang, Youmin Shu, Donghui Ma, Wei-Wu He, Jian Chen. Using protein chips to develop a highly specific HER2 antibody for HER2 amplification testing. [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 3399. doi:10.1158/1538-7445.AM2015-3399
Deep Vein Thrombosis in Myeloma: Estimate of Prevelance and Recommendations for Therapy Based upon a Survey of Members of the International Myeloma Working Group (IMWG).
Authors: Brian G.M. Durie, Paul Richardson, Antonio Palumbo, Meletios A. Dimopoulos, Michele Cavo, Roman Hajek, Douglas E. Joshua, Kazuyuki Shimizu, Guido J. Tricot, Morie Gertz, Patrizia Tosi, David H. Vesole, Mohamad A. Hussein, Heinz Ludwig, Hartmut Goldschmidt, J.F. San Miguel, Pieter Sonneveld, S. Vincent Rajkumar
Journal: Blood (2006)
Abstract P3-07-27: Patterns of chemotherapy (CT) use by molecularly-defined subtype among a population-based cohort of breast cancer (BC) patients (pts) from California
Authors: Christina A Clarke, Laura Chu, Lisa Wang, Chunyan Song, Marjorie Green, Lisa Moy, Juan Yang, Li Tao, Scarlett Lin Gomez
Journal: Cancer Research (2015)

Abstract Background: Guidelines describe recommended BC treatments (tx) according to tumor subtype; however, population-based data regarding tx utilization are limited. Objective: To describe tx utilization by tumor HER2, hormone receptor (HR) status, and stage among representative pts from California. Methods: We examined patterns of CT (including biologic tx) reported as received for all 131,450 female BC pts diagnosed with primary invasive BC in California between 1/1/2005 and 12/31/2011 in the California Cancer Registry, including n=19,918 HER2+ [65% HR+, 33% HR-]; n=91,919 HER2- [84% HR+, 15% HR-]; and n=19,613 HER2 unknown. Neoadjuvant &amp; adjuvant CT data was only available for a subset of 35,040 pts diagnosed 2010-2011 (4,609 HER+; 27, 604 HER2-). Descriptive statistics were used for comparisons. Results: CT was reported as highest among pts with metastatic breast cancer (MBC) and HER2+ status (Table 1). The proportion of pts with early BC (EBC) receiving CT increased from 58% in 2005 to 69% in 2010, but was generally steady for MBC pts (74.2% in 2005 to 79.6% in 2011). 20.7% of HER2+ pts received neoadjuvant CT vs 8.6% for HER2- pts. Similarly, adjuvant CT was more common in HER2+ (55.5%) than HER2- (28.5%) pts. As expected the proportion of pts receiving CT was lower in HR+ vs HR- pts for EBC and MBC [eg. all stages HER2+ (62% vs 71%); HER2- (33% vs 68%)]. Conclusion: In this population-based cohort, ∼20-40% of MBC pts may not have received any CT or biologics. CT was more commonly received by HER2+ patients compared to HER2- patients for both EBC and MBC. Table 1. Patterns of chemotherapy (including biologics) use among California female BC pts by stage and HER2 status, 2005-2011EBCMBCHER2+HER2-HER2+HER2-Any chemotherapyNo5898 (33.4%)52467 (61.0%)317 (22.6%)1519 (43.7%)Yes11463 (64.8%)32403 (37.7%)1063 (75.9%)1894 (54.5%)Unknown322 (1.8%)1128 (1.3%)20 (1.4%)60 (1.7%)Any neoadjuvant therapy (2010-2011 data only)No3546 (76.9%)24794 (89.8%)**Yes953 (20.7%)2381 (8.6%)**Unknown110 (2.4%)429 (1.6%)**Any adjuvant therapy (2010-2011 data only)No1943 (42.2%)19296 (69.9%)**Yes2556 (55.5%)7879 (28.5%)**Unknown110 (2.4%)429 (1.6%)*** not applicable Citation Format: Christina A Clarke, Laura Chu, Lisa Wang, Chunyan Song, Marjorie Green, Lisa Moy, Juan Yang, Li Tao, Scarlett Lin Gomez. Patterns of chemotherapy (CT) use by molecularly-defined subtype among a population-based cohort of breast cancer (BC) patients (pts) from California [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P3-07-27.
Autologous Stem Cell (AUTO) vs Non-Myeloablative Allogeneic Transplantation (NMT) after High-Dose Rituximab (HD-R) -Containing Conditioning Regimens for Relapsed Chemosensitve Follicular Lymphoma (FL).
Authors: Issa F. Khouri, Rima M. Saliba, Chitra M. Hosing, Sandra A. Acholonu, Luis E. Fayad, Martin J. Korbling, Celina Saenz, Barbara Pro, Barry I. Samuels, Marcos J. de Lima, Sergio A. Giralt, Anas Younes, Peter W. McLaughlin, Richard E. Champlin
Journal: Blood (2005)
PWE-022 Can fibre improve bowel function in inflammatory conditions of the rectum? A pilot study in prostate cancer patients receiving radiotherapy
Authors: L Wedlake, H McNair, G McVie, K Thomas, D Dearnaley, J Andreyev
Journal: Gut (2010)

Introduction The anti-inflammatory role of dietary fibre, its impact on bowel frequency and stool consistency is inadequately studied. Therapeutic radiotherapy for prostate cancer provides a unique opportunity to assess the potential efficacy of fibre in protecting the rectum from cumulative, radiation-therapy induced, inflammatory insults. The rectum inevitably receives some radiation dose during prostate irradiation. Rectal function in most men, will be normal before the radiotherapy starts and a predictable inflammatory response occurs during radiotherapy which peaks during the second week of treatment, causing the worst symptoms by the fourth to fifth weeks. We investigated whether patients could follow a fluid and fibre prescription designed to regularise bowel habit commencing before and continuing for the 6–9 weeks of radiotherapy. Additionally, the effect of the diet on gastrointestinal symptoms, rectal distension and stool consistency was examined. Methods Fibre and fluid intake was assessed at baseline and individualised prescriptions given to regularise frequency of bowel motion to at least 1 motion/day and ensure adequate fluid intake. Compliance was measured daily as was stool frequency and type (consistency) using the Bristol Stool Form 7-point scale. Symptoms were assessed at baseline and at end-RT (end of radiotherapy) using a modified IBDQ (Inflammatory Bowel Disease Questionnaire) and IBDQ-B, bowel subset. Rectal gas (5-point scale) and distension (rectal Cross Sectional Area in cm2) defined as rectal volume/length were measured throughout treatment from serial CT scans. Result 22 patients were invited to participate. 21 (median: 71 years; range: 59–82 years) provided evaluable data. Between baseline and end-RT, 14 patients increased fibre intake (NSP: Englyst) and seven decreased intake (5 g/day and -2 g/day, respectively). 13 patients exceeded and eight patients did not meet their prescribed fibre intake. Stool frequency increased from mean 1.9 to 2.4 motions/day at end-RT. The mean fall in IBDQ-B scores (n=21) was 10.8 points which was similar in both the increasing and decreasing fibre groups (10.3 vs 11.6 points, respectively). The mean fall in IBDQ scores was twofold greater in the decreasing fibre group compared to increasing (34.6 vs 17.6, respectively). Rectal distension was significantly correlated with rectal gas (p=0.04) but was not associated with change in fibre intake. Mean rectal CSAcm2 decreased from 7.5 cm2 at baseline to 6.8 cm2 at end-RT. Conclusion Patients are able to follow fibre prescriptions based on normally-consumed foods for prolonged periods but there is a tendency to exceed dose and therefore it is important to set upper limits. Increased fibre intake (25% more than habitually consumed) appeared to offer protection from symptoms and did not have an adverse effect on rectal gas, distension, stool frequency or consistency.
Abstract 4032: Functional analysis of exosomes derived from human esophageal squamous cell carcinoma
Authors: Yasunori Matsumoto, Masayuki Kano, Yasunori Akutsu, Takanori Nishimori, Naoyuki Hanari, Isamu Hoshino, Kentaro Murakami, Takeshi Toyozumi, Hiroshi Suito, Masahiko Takahashi, Nobufumi Sekino, Yoshihiro Nabeya, Hisahiro Matsubara
Journal: Cancer Research (2015)

Abstract Exosomes are small membrane vesicles (30-100 nm) released by many types of cells including cancer cells, and are thought to play an important role in cell-to-cell communications. Exosomes contain lipids, proteins, and nucleic acids such as mRNAs or microRNAs, they are tought to have relationship with tumor growth or metastasis. Our laboratory was previously reported the level of microRNA-1246, expressed mainly in tumor tissues of esophageal squamous cell carcinoma (ESCC), was significantly high in exosomes extracted from the serum of ESCC patients. However, the exosome dynamics and transportation between cancer cells and the other cells are still unclear. In this study, we assessed the cell-to-cell communication via exosomes with fluorescent imaging and analyzed the effect of cancer cell derived exosome to tumor progression. In order to image and analyze the movement of cancer cell-derived exosomes, green fluorescent protein (GFP)-tagged CD63, which is a general marker of exosomes, was expressed in human esophageal squamous cancer cell line TE2. Exosomes were extracted from supernatant with ultracentrifuge method. Extracted GFP-tagged exosomes were added to the other cells to obtain the images of transportation. The effects of exosomes to tumor progression were also assessed with cell proliferation assay, invasion oassay, and migration assay. Our data indicates that cancer cell derived exosomes affect tumor progression. Citation Format: Yasunori Matsumoto, Masayuki Kano, Yasunori Akutsu, Takanori Nishimori, Naoyuki Hanari, Isamu Hoshino, Kentaro Murakami, Takeshi Toyozumi, Hiroshi Suito, Masahiko Takahashi, Nobufumi Sekino, Yoshihiro Nabeya, Hisahiro Matsubara. Functional analysis of exosomes derived from human esophageal squamous cell carcinoma. [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 4032. doi:10.1158/1538-7445.AM2015-4032
613. Characterization of IPSC-Derived Myogenic Progenitors Isolated from Mouse Models of Duchenne Muscular Dystrophy
Authors: Niclas E. Bengtsson, John K. Hall, André M. Lieber, Jeffrey S. Chamberlain
Journal: Molecular Therapy (2015)

Duchenne muscular dystrophy (DMD) affects approximately 1 in 5000 children and is characterized by progressive muscle wasting, weakness and premature death. DMD is caused by mutations in the gene encoding dystrophin, which plays an essential role in maintaining muscle integrity by providing a structural link between the cytoskeleton and the extracellular matrix. In the absence of dystrophin, affected muscles experience repeated bouts of injury, inflammation and necrosis, resulting in reduced regenerative capacity and the replacement of muscle mass with fibrotic and adipose tissue. Both gene and cell therapies are candidate approaches to replace the defective dystrophin gene. While gene therapy has the potential to halt disease progression in targeted muscles, cell therapies could both introduce replacement genes and generate new muscle or muscle stem cells to affected tissues. Cell therapies for DMD have thus far shown moderate success due to limited ex vivo expansion potential of progenitor cells, poor survival and migration of cells following transplantation, inefficient myogenic conversion of non-myogenic cells as well as host rejection of donor cells. Most of these limitations could potentially be addressed using gene corrected induced pluripotent stem (iPS) cells derived from biopsies of affected patients. We have established and characterized several iPSC lines from control, dystrophic (mdx) and transgenic-mdx mice. Selected iPS cells expressed markers associated with pluripotency, exhibited normal karyotypes and were able to form all three germ layers during in vivo teratoma assays. To generate myogenic progenitors from iPS cells, we have investigated the use of an inducible form of the myogenic regulatory factor MyoD (MyoD-ER[T]). Upon transient activation of MyoD-ER[T], iPSCs are readily converted into myogenic progenitor cells that can efficiently differentiate into myocytes and fuse into myotubes in vitro. iPS cells derived from dystrophic mice and which carry different versions of dystrophin expression cassettes can engraft into mdx muscles in vivo and generate dystrophin-positive myofibers. We are currently comparing the efficiency of various myogenic cell populations resulting from MyoD-ER[T] induction to generate functional myogenic engraftment in vivo following transplantation into mdx mouse hosts. We are also comparing the relative efficiency of dystrophin production in myogenic cells derived from mdx iPSCs using gene replacement vs. gene modification approaches. Together, these approaches show potential for ex vivo gene therapy of DMD using dystrophin-corrected autologous cell transplantation.
Thalidomide and Dexamethasone Induction Therapy Is Associated with Superior Progression-Free Survival after Autotransplant for Myeloma.
Authors: Dan T. Vogl, Selina Luger, David L. Porter, Elise A. Chong, Stephen J. Schuster, Donald E. Tsai, Alexander Perl, Alison W. Loren, Stephen Goldstein, Sunita D. Nasta, Charalambos Andreadis, Patricia A. Mangan, Kimberly Hummel, Donald L. Siegel, Eli Glatstein, Edward A. Stadtmauer
Journal: Blood (2005)
Community Based Evaluation of Prevalence of Inhibitors in Patients with Severe Hemophilia A in India and Their Correlation with Environmental and Genetic Factors
Authors: Sachin David, Vikram Mathews, Shashikant Apte, Giridhara R Jayandharan, Sukesh C Nair, Dolly Daniel, Suresh Kumar, Ansu Abu Alex, Saravanan Ganesan, Kannan Subramanian, Rayaz Ahmed, Aby Abraham, Auro Viswabandya, Biju George, Alok Srivastava
Journal: Blood (2012)
Biomechanical CT metrics are associated with patient outcomes in COPD
Authors: Sandeep Bodduluri, Surya P Bhatt, Eric A Hoffman, John D Newell, Carlos H Martinez, Mark T Dransfield, Meilan K Han, Joseph M Reinhardt
Journal: Thorax (2017)

Traditional metrics of lung disease such as those derived from spirometry and static single-volume CT images are used to explain respiratory morbidity in patients with COPD, but are insufficient. We hypothesised that the mean Jacobian determinant, a measure of local lung expansion and contraction with respiration, would contribute independently to clinically relevant functional outcomes.We applied image registration techniques to paired inspiratory-expiratory CT scans and derived the Jacobian determinant of the deformation field between the two lung volumes to map local volume change with respiration. We analysed 490 participants with COPD with multivariable regression models to assess strengths of association between traditional CT metrics of disease and the Jacobian determinant with respiratory morbidity including dyspnoea (modified Medical Research Council), St Georges Respiratory Questionnaire (SGRQ) score, 6-min walk distance (6MWD) and the Body Mass Index, Airflow Obstruction, Dyspnoea and Exercise Capacity (BODE) index, as well as all-cause mortality.The Jacobian determinant was significantly associated with SGRQ (adjusted regression coefficient β=-11.75,95% CI -21.6 to -1.7; p=0.020), and with 6MWD (β=321.15, 95% CI 134.1 to 508.1; p<0.001), independent of age, sex, race, body mass index, FEV1, smoking pack-years, CT emphysema, CT gas trapping, airway wall thickness and CT scanner type. The mean Jacobian determinant was also independently associated with the BODE index (β=-0.41, 95% CI -0.80 to -0.02; p=0.039) and mortality on follow-up (adjusted HR=4.26, 95% CI 0.93 to 19.23; p=0.064).Biomechanical metrics representing local lung expansion and contraction improve prediction of respiratory morbidity and mortality and offer additional prognostic information beyond traditional measures of lung function and static single-volume CT metrics.NCT00608764; Post-results.
Abstract 178: Targeting of multiple oncogenic miRNAs on NUMB gene to mediate head and neck carcinogenesis
Authors: Chung-Shan Chou, Kuo-Wei Chang, Shu-Chun Lin
Journal: Cancer Research (2015)

Abstract Head and neck squamous cell carcinoma (HNSCC) is the 6th leading malignancy in the world. MicroRNAs (miRNAs) are small, non-coding RNAs, which are associated with the genesis and progression of cancers. NUMB is a multi-functional adaptor protein, which can activate E3 ubiquitin ligase and degrade target proteins to modulate pathogenesis. In silico modules predict that miR-31, miR-96, miR-182 and other miRNAs might target NUMB. This study investigates the concordant targeting of multiple oncogenic miRNAs to NUMB, and to verify the roles of NUMB in HNSCC. miR-31, miR-96 and miR-182 were found up-regulated in the vast majority of HNSCC tissues. On the contrary, NUMB expression was largely down-regulated in the tumors. A reverse correlation was noted between miR-31 expression and NUMB expression. Reporter assays using wild type and mutant constructs specified that these oncogenic miRNAs directly target the sequences in the 3′UTR of NUMB gene. However, miR-31 was unable to target a predicted site in the coding sequence of NUMB gene to mediate regulation. Exogenous expression of these miRNAs decreased NUMB expression and increased the migration of HNSCC cells. Knockdown of NUMB expression enhanced oncogenicity of HNSCC cells. However, the exogenous NUMB expression decreased the migration and anchorage-independent growth of HNSCC cells. The oncogenicity induced by these oncogenic miRNAs was attenuated by NUMB expression. This study provides in vitro and in vivo clues demonstrating that miR-31, miR-96 and miR-182 co-target NUMB gene in HNSCC. The coordinative abrogation of these miRNAs together with NUMB enhancement may be contributive to new therapeutic intervention against head and neck cancers. Citation Format: Chung-Shan Chou, Kuo-Wei Chang, Shu-Chun Lin. Targeting of multiple oncogenic miRNAs on NUMB gene to mediate head and neck carcinogenesis. [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 178. doi:10.1158/1538-7445.AM2015-178
Patterns of Immune Infiltration in Breast Cancer and Their Clinical Implications: A Gene-Expression-Based Retrospective Study
Authors: H. Raza Ali, Leon Chlon, Paul D. P. Pharoah, Florian Markowetz, Carlos Caldas
Journal: PLoS Medicine (2016)

Background Immune infiltration of breast tumours is associated with clinical outcome. However, past work has not accounted for the diversity of functionally distinct cell types that make up the immune response. The aim of this study was to determine whether differences in the cellular composition of the immune infiltrate in breast tumours influence survival and treatment response, and whether these effects differ by molecular subtype. Methods and Findings We applied an established computational approach (CIBERSORT) to bulk gene expression profiles of almost 11,000 tumours to infer the proportions of 22 subsets of immune cells. We investigated associations between each cell type and survival and response to chemotherapy, modelling cellular proportions as quartiles. We found that tumours with little or no immune infiltration were associated with different survival patterns according to oestrogen receptor (ER) status. In ER-negative disease, tumours lacking immune infiltration were associated with the poorest prognosis, whereas in ER-positive disease, they were associated with intermediate prognosis. Of the cell subsets investigated, T regulatory cells and M0 and M2 macrophages emerged as the most strongly associated with poor outcome, regardless of ER status. Among ER-negative tumours, CD8+ T cells (hazard ratio [HR] = 0.89, 95% CI 0.80–0.98; p = 0.02) and activated memory T cells (HR 0.88, 95% CI 0.80–0.97; p = 0.01) were associated with favourable outcome. T follicular helper cells (odds ratio [OR] = 1.34, 95% CI 1.14–1.57; p < 0.001) and memory B cells (OR = 1.18, 95% CI 1.0–1.39; p = 0.04) were associated with pathological complete response to neoadjuvant chemotherapy in ER-negative disease, suggesting a role for humoral immunity in mediating response to cytotoxic therapy. Unsupervised clustering analysis using immune cell proportions revealed eight subgroups of tumours, largely defined by the balance between M0, M1, and M2 macrophages, with distinct survival patterns by ER status and associations with patient age at diagnosis. The main limitations of this study are the use of diverse platforms for measuring gene expression, including some not previously used with CIBERSORT, and the combined analysis of different forms of follow-up across studies. Conclusions Large differences in the cellular composition of the immune infiltrate in breast tumours appear to exist, and these differences are likely to be important determinants of both prognosis and response to treatment. In particular, macrophages emerge as a possible target for novel therapies. Detailed analysis of the cellular immune response in tumours has the potential to enhance clinical prediction and to identify candidates for immunotherapy.
Synergistic Growth Inhibition by the Combination of Acyclic Retinoid Plus Vitamin K2 in HL-60 Cells
Authors: Junichi Kitagawa, Senji Kasahara, Takeshi Hara, Nobuhiro Kanemura, Masahito Shimizu, Hisashi Tsurumi, Hisataka Moriwaki
Journal: Blood (2008)