tbuckley/cabot-search huggingface dataset:
Abstract 710: CRP induction in tamoxifen-resistant breast cancer cells
Authors: Min Chang Choi, Aree Moon, Keon Wook Kang
Journal: Cancer Research (2015)

Abstract Breast cancer is one of the most common cancer types among post-menopausal women. Tamoxifen has been known as the most effective therapeutic option for estrogen receptor-positive breast cancer. One of the main issues of breast cancer is acquisition of tamoxifen resistance, and if it does, the way to treat tamoxifen-resistant breast cancer has not been discovered. It has been recently suggested that c-reactive protein (CRP), inflammatory marker found in many diseases may be related to breast cancer progression. Here, we found that tamoxifen-resistant breast cancer (TAMR-MCF-7) cells expresses much higher protein and mRNA level of CRP compared to parent breast cancer (MCF-7) cells. CRP knock-down by lentiviral shRNA did not affect cell proliferation rate of TAMR-MCF-7 cells. One of the main characteristics of tamoxifen-resistant breast cancer is higher migratory ability. Through trans-well migration assay, we have discovered that CRP alone increases migratory function of MCF-7 cells. Moreover, CRP knock-down significantly reduced cell migration of TAMR-MCF-7 cells. It has been recently reported that sphingosine-1-phosphate (S1P) induces CRP in mammary epithelial cells and ultimately causes cancer cell transformation. S1P treatment increased CRP expression in MCF-7 cells. Protein expression of sphingosine kinase (Sphk) 1 and 2, which catalyzes conversion of sphingosine to S1P, was also increased in TAMR-MCF-7 cells. Among five S1P receptors, we also discovered that S1P receptor 3 (S1Pr3) is related with CRP induction in TAMR-MCF-7 cells. Taken together, tamoxifen-resistant breast cancer expresses high level of CRP and S1P-S1Pr3 plays a key role in CRP induction in TAMR-MCF-7 cells. Higher levels of CRP increases migratory function of tamoxifen-resistant breast cancer cells. CRP may be an important therapeutic target for the treatment of tamoxifen-resistant breast cancer. Citation Format: Min Chang Choi, Aree Moon, Keon Wook Kang. CRP induction in tamoxifen-resistant breast cancer cells. [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 710. doi:10.1158/1538-7445.AM2015-710
New Insights into the Function of N-Terminal 11 Amino Acids of Band 3 from Structural and Functional Study of a Naturally Occuring Band 3 Variant.
Authors: Silverio Perrotta, Borriello Adriana, Lucia De Franceschi, Bruno Nobili, Achille Iolascon, Anna Maria Brunati, Francesca Rossi, Francesco Turrini, Fulvio Della Ragione, Philip Low, Narla Mohandas
Journal: Blood (2004)
From the authors
Authors: J. Cohen, N. R. Douma, N. H. T. ten Hacken, D. S. Postma
Journal: European Respiratory Journal (2008)

Assessing small airways diseaseTo the Editors:In their excellent study of the effect of small particle corticosteroids on small airway involvement in asthma, COHEN et al. [1], along with LAHZAMI and KING [2] in the accompanying lead editorial [2], decry the complexity associated with current measurements of small airways function.Those authors stress the desirability of finding simpler methods to assess small airways dysfunction.A simple method of assessing smaller airways obstruction is easily available and could be used retrospectively.In contrast to the mean forced expiratory flow between 25 and 75% of forced vital capacity (FVC; FEF25-75%), which measures the mid-portion of exhalation ending at nearly the same time as the forced expiratory volume in one second (FEV1) in these subjects, the FEV3/FVC% or (1-FEV3/FVC)% are excellent measures of small airways function.They measure the fraction of volume exhaled near the end of a forced exhalation, i.e. from airspaces and airways with the longest time constants [3,4].However, because they are ratios (as are FEV1/FVC and FEF25-75%) they are not ideal measurements of airway responsiveness to bronchodilators.Rather, pre-and post-absolute volumes, such as FEV1, FEV3 and FEV6, should be compared to assess bronchodilator effect.Presumably, if there is a small airways bronchodilator effect in the ciclesonide-treated group, the increase from pre-to post FEV3 (DFEV3) or FEV6 (DFEV6) should exceed that of pre-to post-FEV1 (DFEV1).For example, if the DFEV1 was 150 mL and the DFEV3 and DFEV6 were also 150 mL, the dominant change was in the larger airways.If the DFEV1 was 150 mL and the DFEV3 and DFEV6 were 200-250 mL, there was also an important change in the smaller airways.These simple measurements would objectively disclose whether the smaller airways were directly affected by the ciclesonide.It would be of interest and importance if COHEN et al. [1] and other authors would retrospectively or prospectively measure and report these findings to see whether these simple, quick and inexpensive measures are useful in evaluating drugs that modify small airways obstruction.
SNP Array-Based Analysis of Chromosome 17 Reveals Biallelic TP53 Mutations Due to Uniparental Disomy 17p in Advanced MDS and AML with Cooperating Deletions of Chromosomes 5 and 7
Authors: Monika Jasek, Lukasz P. Gondek, Nelli Bejanyan, Ramon V. Tiu, Jungwon Huh, Karl S. Theil, Christine O’ Keefe, Michael A. McDevitt, Jaroslaw P. Maciejewski
Journal: Blood (2008)
Oral etoposide monotherapy for Chinese patients with metastatic breast cancer: Efficacy and tolerance regardless of heavy prior therapy.
Authors: P. Yuan, B. Xu, F. Ma, J. Wang, Y. Fan
Journal: Journal of Clinical Oncology (2011)

1107 Background: Effective treatment options for metastatic breast cancer (MBC) patients heavily pretreated with chemotherapy are limited. Oral etopside 50mg/m2/daily for consecutive 21 days among 28 days has single-agent activity in these patients. However, the patients who have received heavy prior chemotherapy may have poor tolerance to prolonged oral etoposide for 21 days. Dosage and usage of oral etoposide remain uncertain. This study was designed as a prospective clinical trial to evaluate the efficacy and safety of short-term oral etoposide in Chinese patients with MBC who had received heavy prior therapy. Methods: Patients with measurable disease who had been previously treated with at least 2 chemotherapy regimens were treated with oral etoposide at 60 mg/m2 on day 1 to day 10 of a 21 day cycle. The primary end point was the progression free survival (PFS). The secondary end points were objective response rate (ORR), clinical benefit rate (CBR), overall survival (OS), and toxicity profiles. Results: Thirty-two patients received 230 cycles with a median of 6 cycles (range, 2 to 20 cycles) per patients. 8 patients (25%) had partial response (PR), 14 patients achieved stable disease (SD) and the ORR was 25%. 9 patients achieved SD for more than 24 weeks and CBR was 53%. Medium PFS was 5 months. The medium OS was 16 months (range, 3-51months). The patients achieved clinical benefit had longer survival time than those didn’t (25.0 verses 11.0 months, p<.01). Among the 16 patients who have received more than 4 previous regimens treatment, 4 patients got PR, and 4 patients achieved SD for more than 24 weeks, which lead to a CBR of 50%. The most common hematologic adverse events were anemia (43.8%) and neutropenia (38.5%), whereas nausea/vomiting (75.0%) and alopecia (62.5%) were the most frequent non-hematologic toxicity. Conclusions: These data demonstrate that oral etoposide given for 10 days of a 21-day cycle is effective and represents a well-tolerated treatment option for Chinese women with heavily pretreated MBC.
A transistor-like pH nanoprobe for tumour detection and image-guided surgery
Authors: Tian Zhao, Gang Huang, Yang Li, Shunchun Yang, Saleh Ramezani, Zhiqiang Lin, Yiguang Wang, Xinpeng Ma, Zhiqun Zeng, Min Luo, Esther de Boer, Xian-Jin Xie, Joel Thibodeaux, Rolf A. Brekken, Xiankai Sun, Baran D. Sumer, Jinming Gao
Journal: Nature Biomedical Engineering (2016)
HSV-TK Engineered Donor Lymphocytes Add-Backs Reduce Late Mortality and Improve Survival of High Risk Acute Leukemia after Haplo-HSCT: Results of a Phase II Multicenter Trial.
Authors: F. Ciceri, C. Bonini, M.T. Lupo Stanghellini, A. Bondanza, Z. Magnani, S. Perna, M. Bernardi, J. Peccatori, A. Pescarollo, P. Servida, F. Crippa, L. Callegaro, M. Salomoni, L. Turchetto, S. Toma, P. Bruzzi, L. Castagna, A. Santoro, J. Apperley, S. Slavin, S. Colombi, C. Gallo Stampino, M. Bregni, C. Bordignon
Journal: Blood (2005)
Randomized phase II trial evaluating different schedules of zoledronic acid administration on bone mineral density in patients with stage D prostate cancer beginning androgen deprivation.
Authors: J. M. Lang, J. C. Eickhoff, N. C. Binkley, M. J. Staab, G. Liu, G. Wilding, D. G. McNeel
Journal: Journal of Clinical Oncology (2011)

4643 Background: Androgen deprivation therapy (ADT), the primary treatment for patients (pts) with metastatic prostate cancer (PC), causes bone loss. Zoledronic acid (ZA) is FDA approved for the treatment of bone metastatic PC, and in that setting is typically used on an every 3-4 week schedule. ZA is also approved for osteoporosis treatment in which setting it is typically used once per year. Methods: In this trial we evaluated changes in bone mineral density (BMD) following 3 different schedules of ZA administration in pts with recurrent PC who were beginning ADT. 44 pts were enrolled and randomized to one of 3 different treatment arms. 14 pts were treated once with 4 mg ZA one week prior to beginning ADT (arm A); 15 pts were treated once with 4 mg ZA 6 mo after beginning ADT (arm B); and 15 pts were treated monthly with 4 mg ZA for six mo beginning six mo after starting ADT (arm C). BMD measurements of the lumbar spine (LS) and femur by dual energy x-ray absorptiometry were assessed at baseline, and after 6, 12, 18 and 24 mo. As of March 2011, all pts will have completed 24 mo of follow up. Results: In pts treated on arm A, BMD increased from baseline to 6 mo at the total proximal femur (TPF) (+1.1% +/- 1.9%) that was significantly greater than the loss of BMD observed over the same period in patients in Arm B (-0.2% +/- 1.6%, p=0.05) or Arm C (-0.6% +/- 2.0%, p=0.01). Similar trends were observed at other measured sites. At 24 months, increases in BMD were greatest in pts treated on Arm C (1.5% +/- 3.3% at the TPF), compared with Arm B (0.12% +/- 2.0%) or Arm A (-0.9% +/- 2.6%). AEs believed at least possibly related to ZA consisted of grade 1 constitutional symptoms, grade 1 or 2 musculoskeletal symptoms, and grade 1 insomnia or irritability. Conclusions: Overall, these data demonstrate that BMD loss occurs within months after beginning ADT, and early administration of ZA may prevent significant BMD loss. Consequently the timing of ZA administration may be important for men initiating ADT. Furthermore, ZA administration results in a delayed increase in BMD in patients previously started on ADT.
620. Cancer Associated Fibroblasts-Targeted Oncolytic Virus Results in Enhanced Antitumor Activity in Mouse Model
Authors: Feng Yu, Bangxing Hong, Xiaotong Song
Journal: Molecular Therapy (2015)

Oncolytic vaccinia virus (VV) therapy has shown promise in preclinical models and in clinical studies. However, complete responses have rarely been observed. Targeting cancer-associated fibroblasts (CAFs) in addition to cancer cells may enhance antitumor effects, since CAFs, the central component of the tumor stroma, directly support tumor growth and contribute to the immunosuppressive tumor microenvironment. To target CAFs we developed a new oncolytic vaccinia virus that encodes a secretory bispecific T-cell engager consisting of two single- chain variable fragments specific for CD3 and the fibroblast activation protein (FAP) (FAP-T-cell engager-armed VV (FAP-TEA-VV)). FAP-TEA-VV induced robust FAP- and TRP2-specific T-cell responses in tumor environment, resulting in greater antitumor activity in the B16 melanoma model in comparison to unmodified VVs. FAP-TEA-VV enhanced tumor infiltration of CD8-positive T cells, and enhanced virus spread with tumors. Thus, targeting of CAFs has the potential to improve current virus therapy for cancer.
Abstract 732: Using functional and chemical genomics to identify mechanisms of Enzalutamide resistance in prostate cancer
Authors: Sujeeve Jeganathan, Amina Zoubeidi, Martin Gleave, Brad G. Wouters, Anthony M. Joshua
Journal: Cancer Research (2015)

Abstract Introduction: Enzalutamide is a recently approved potent androgen receptor antagonist for prostate cancer both in the pre- and post-docetaxel settings. Its action relies upon 3 defined mechanisms of action: 1) blocking testosterone binding to the androgen receptor (AR), 2) preventing nuclear translocation of AR, and 3) inhibiting AR-DNA binding. However, despite its utility in prolonged overall survival in both these settings, disease relapse is inevitable, suggesting that resistance to the drug is somehow being acquired and is of vital concern. Methods: Using a combination of high-throughput functional genomic (kinome-shRNA) and chemical genomic (pharmacological inhibitor) screens, along with various in vitro / in vivo assays (proliferation, apoptosis, necrosis, soft agar growth, etc.) we have identified the IkB kinase (IKK) / IkB / NFkB signaling axis as important for acquisition of, and continued resistance to, Enzalutamide. Results: Using a panel of Enzalutamide-resistant and -sensitive cell lines, we show that targeting this signaling axis will selectively kill Enzalutamide-resistant cells while not affecting the proliferation of sensitive cells. Moreover, our data shows that the pharmacological inhibitors and shRNAs are effective even without Enzalutamide administration, negating any potential drug-drug interaction issues. Finally, we have found that our cells are resistant to Enzalutamide in an AR-V7-independent manner, suggesting that NFkB signaling is acting in a novel manner to bring about the resistance phenotype. Conclusions: Through in vitro and in vivo experiments, we provide evidence that targeting activators of NFκB signalling can be a strategy to help patients with Enzalutamide-resistant prostate cancer. Note: This abstract was not presented at the meeting. Citation Format: Sujeeve Jeganathan, Amina Zoubeidi, Martin Gleave, Brad G. Wouters, Anthony M. Joshua. Using functional and chemical genomics to identify mechanisms of Enzalutamide resistance in prostate 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 732. doi:10.1158/1538-7445.AM2015-732
Protein Phosphatase 2B Inhibition Promotes the Secretion of Von Willebrand Factor from Endothelial Cells
Authors: Leticia Nolasco, Francisca C. Gushiken, Vimal Patel, Nancy Turner, Subhashree Pradhan, Jing-fei Dong, Joel L. Moake, K. Vinod Vijayan
Journal: Blood (2008)
Abstract 4394: Selective accumulation and specific tumor damage by folate receptor-targeted CA-4 prodrug as part of a combination of photodynamic therapy and site-specific chemotherapy
Authors: Nkepang Gregory, Moses Bio, Pallavi Rajaptura, Samuel G. Awuah, Youngjae You
Journal: Cancer Research (2015)

Abstract A non-invasive or minimally invasive tumor ablation regimen is an attractive tool with which to control tumors. This approach is complementary to primary treatment options without causing systemic side effects or severe physical burdens from the treatment itself. Clinically approved photodynamic therapy (PDT) is one such regimen. In PDT, photosensitizers are activated by visible and near IR light to destroy tumors. However, the therapeutic efficacy of PDT is limited due to the spatial and temporal restrictions of the effector of PDT, singlet oxygen. We have been developing a new prodrug strategy that can overcome these limits by using a unique combination of PDT and site-specific chemotherapy. The prodrug is composed of photosensitizer and anticancer drug via a singlet oxygen-cleavable linker. Upon illumination, the prodrugs cause PDT damage and simultaneously release anticancer drugs only at the illuminated target area. In our previous publications, we reported 1) the design and synthesis of prodrugs of combretastatin A-4, 2) visible/ near IR light-controlled release of the drug from the prodrug, 3) bystander effects from the released anticancer drug, and 4) the superior antitumor effect of the prodrug compared to a simple combination of PDT and chemotherapy. Recently, a more advanced CA-4 prodrug was developed to achieve selective delivery to tumors via folate receptors (FRs) overexpressed in numerous cancer cell lines. The targeted prodrug showed FR-mediated uptake to FR-expressing cancer cells (colon 26 cells) in vitro and to FR-expressing tumors in vivo. Notably, the targeted CA-4 prodrug effectively ablated the tumors without causing collateral damage to the surrounding skin. Citation Format: Nkepang Gregory, Moses Bio, Pallavi Rajaptura, Samuel G. Awuah, Youngjae You. Selective accumulation and specific tumor damage by folate receptor-targeted CA-4 prodrug as part of a combination of photodynamic therapy and site-specific chemotherapy. [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 4394. doi:10.1158/1538-7445.AM2015-4394
Sequential Evaluation of Outcome in Enteropathy Associated T Cell Lymphoma Comparing Standard Therapeutic Approaches – Surgery or CHOP-Like Chemotherapy with a New High Dose Ifosfamide/Methotrexate and Autologous Stem Cell Transplant Regimen: A Prospective Study of Scotland and Newcastle Lymphoma Group
Authors: Michal Sieniawski, Nithia Angamuthu, Kathryn Boyd, Richard Chasty, John Davies, Paul Revell, Stephen J Proctor, Anne L Lennard
Journal: Blood (2008)
Rituximab Maintenenance Therapy in CD20+ B-Cell Non-Hodgkin-Lymphoma - First Interim Results of a Prospective Randomised Phase II Study.
Authors: Mathias Witzens-Harig, Manfred Hensel, Kai Neben, Axel Benner, Johann W. Schmier, Peter Dreger, Alwin Kraemer, Anthony D. Ho
Journal: Blood (2005)
Obesity increases the risk of end-stage renal disease among living kidney donors
Authors: Jayme E. Locke, Rhiannon D. Reed, Allan Massie, Paul A. MacLennan, Deirdre Sawinski, Vineeta Kumar, Shikha Mehta, Roslyn B. Mannon, Robert Gaston, Cora E. Lewis, Dorry L. Segev
Journal: Kidney International (2016)
Abstract LB-120: HER2 as a potential predictive marker and target for therapy in cervical cancer
Authors: Mari K. Halle, Akinyemi I. Ojesina, Ingvild L. Tangen, Frederik Holst, Hilde R. Engerud, Bjørn I. Bertelsen, Camilla Krakstad, Helga B. Salvesen
Journal: Cancer Research (2015)

Abstract Cervical cancer is the third leading cause of cancer in the female population worldwide, causing the death of more than 240,000 patients annually in developing countries. Increased molecular knowledge is crucial to identify robust prognostic and predictive biomarkers that can better guide treatment. The tumor response to trastuzumab is well established and strongly links to HER2 expression status evaluated by the Hercep Test, hence, it is essential to define the level of expression of this receptor using the FDA-approved Hercep Test to stratify cervical cancer patients with potential benefits from trastuzumab treatment. Comprehensive molecular characterization has been conducted on 88 paired normal and tumor cases identifying ERBB2 to be frequently altered in cervical cancers. We here explore the protein expression of HER2 by immunohistochemical staining in a larger validation series (n = 220) and relate HER2 expression to the ERBB2 gene alterations, patients molecular profile and clinicopathological features. We find a highly significant correlation between Hercep Test score and mRNA ERBB2 expression (p&amp;lt;0.001). The level of ERBB2 mRNA was also significantly associated with copy number status (p = 0.007). Further clinocopathological parameters like high FIGO stage, high grade, adenocarcinomas and normal p53 status was significantly linked to high HER2 protein expression. Kaplan Meier survival analysis revealed that within the squamous cell carcinomas, high protein levels of HER2 was linked to poorer disease specific survival. Our results show a link between ERBB2 amplification, high mRNA expression and protein levels for HER2 in aggressive cervical cancers. Further studies of HER2 as a potential predictive marker for response to trastuzumab treatment in cervical cancer are needed. Citation Format: Mari K. Halle, Akinyemi I. Ojesina, Ingvild L. Tangen, Frederik Holst, Hilde R. Engerud, Bjørn I. Bertelsen, Camilla Krakstad, Helga B. Salvesen. HER2 as a potential predictive marker and target for therapy in cervical 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 LB-120. doi:10.1158/1538-7445.AM2015-LB-120
Young children risk choking on whole grapes, doctors warn
Authors: Jacqui Wise
Journal: BMJ (2016)

Young children can choke to death when eating whole grapes, doctors have warned in the Archives of Disease in Childhood .1

Amy Lumsden and Jamie Cooper, of the emergency department at Aberdeen Royal Infirmary, UK, described three cases of young children who needed emergency treatment after eating whole grapes, two of whom died. The authors called for greater public awareness about the risk of choking on grapes and said that young children should be supervised while eating.

They also urged the Scottish and UK governments to clearly label foods such as grapes and …
Frequency of axillary node dissection and chemotherapy in breast cancer patients over 60 years of age compared with those younger than 60 years of age
Authors: L. M. Forbes, C. Simmons, T. O'Shea, A. Eisen
Journal: Journal of Clinical Oncology (2004)

8161 Background: Axillary lymph node dissection (ALND) is used to stage breast cancer (BRCA) patients and to select appropriate adjuvant therapy. Older patients may not be offered ALND under the assumption they would not be candidates for chemotherapy. As a result, many patients over age 60 may be undertreated and have an increased risk of BRCA recurrence. The purpose of this study is to compare the rate of chemotherapy and ALND in patients older than 60 years with patients younger than 60 years. Methods: Retrospective chart review of invasive BRCA patients referred for adjuvant treatment at a single academic centre between January 1999 and March 2001. Demographic information, tumour characteristics, surgical and chemotherapy treatment data were collected. Co-morbidity was documented using the Charlson score which assigns 1–2 points for conditions including diabetes, angina, and vascular disease. Results: 293 patients less than 79 years of age were identified. In 166 patients under 60 years, 93.4% received node dissections, 69.3% received chemotherapy and 3.6% declined chemotherapy. However, of 127 patients between 60 and 79 years, 61.5% received axillary dissections, 29.1% received chemotherapy, and 9.5% declined chemotherapy. Average co-morbidity scores for patients less than 60 were 0.14, while those above 60 were slightly higher at 0.54. 7.2% of patients below age 60 had co-morbidities, in comparison 31.5% of those 60–79 had co-morbidities. Of those over 60 years with co-morbidity, the majority had only 1–2 health problems (80%). Tumour size (21 mm vs. 18 mm) and number of lymph nodes in those with ALND (1.1 vs. 0.8) were similar between groups. Conclusions: Although women aged 60–79 did not have a heavy burden of co-morbid illness; they were less likely to receive ALND or chemotherapy. Treatment decisions may be influenced by age rather than by co-morbid status or patient preference in those aged 60–79 who may otherwise be candidates for more aggressive treatment. No significant financial relationships to disclose.