tbuckley/cabot-search huggingface dataset:
An Accumulation of Cytogenetic and Molecular Genetic Events Characterizes the Progression From MDS to Secondary AML: An Analysis of Paired Samples in 38 Patients Analyzed by Cytogenetics, Mutation Analysis and SNP Microarrays.
Authors: Johanna Flach, Sonja Schindela, Frank Dicker, Susanne Schnittger, Beray Kazak, Alexander Kohlmann, Wolfgang Kern, Torsten Haferlach, Claudia Haferlach
Journal: Blood (2009)
Aggressive end-of-life (EOL) chemotherapy (CT) use in metastatic non-small cell lung cancer (mNSCLC): A National Comprehensive Cancer Network (NCCN) outcomes database analysis.
Authors: K. E. Bickel, J. C. Niland, R. Mamet, C. C. Zornosa, D. S. Ettinger, K. Pisters, G. A. Otterson, M. Koczywas, M. E. Reid, M. S. Rabin, T. A. D'Amico, C. Earle, T. M. Pini, G. P. Kalemkerian
Journal: Journal of Clinical Oncology (2011)

7537 Background: Aggressive EOL cancer care is a health care quality and cost issue. As lung cancer is the leading cause of cancer-related death in the U.S., and NCCN member institutions are considered to offer high-quality, evidence-based care, we examined the aggressiveness of mNSCLC EOL care at NCCN institutions. Methods: The NCCN database was queried to identify all deceased mNSCLC patients (pts) actively treated at 8 NCCN institutions from January 2007-June 2010. Aggressive EOL care was defined as 1) Starting a new CT regimen within 30 days of death (30d New), 2) Receipt of CT within 14 days of death (14d Any), or 3) Any ICU admission within the last 30 days of life (30d ICU). Among pts receiving CT, multivariate logistic regression was used to investigate associations between pt factors and aggressive CT use, controlling for age, NCCN institution, performance status (PS), and comorbidity. Multivariate analysis was not possible for the ICU model due to small sample size. Results: Among 1,092 eligible pts, 18.9% had 1 or more aggressive EOL events: 10.7% 30d New, 11.8% 14d Any, and 3.2% 30d ICU. Forty (34%) of 30d New pts started first line CT. Median age overall was 63 (range 25-91) and was 61 for all pts in the aggressive CT analyses. Initial overall PS was 57% 0-1 and was still predominantly 0-1 (23-38%) at the last CT in all groups. The multivariate results are listed below; an odds ratio > 1 indicating aggressive care more likely. Conclusions: While typical pt factors, such as age and PS, are used to determine fitness for CT receipt in mNSCLC, our analysis suggests that aggressive EOL CT receipt in mNSCLC at NCCN institutions is associated with other pt or clinical factors. Analysis Pt factor Odds ratio 95% CI 30 d New* Liver metastasis 1.82 1.19-2.77 Hospice discussion 2.73 1.24-6.04 14 d Any* Prior radiation 1.80 1.17-2.79 ≥2 prior CT regimens 1.79 1.08-2.94 Prior smoker 0.42 0.24-0.73 Current smoker 0.51 0.28-0.94 *No associations seen with other factors, including age, institution, PS, comorbidity, other metastatic sites, clinical trial participation, time from metastatic diagnosis, gender, race, insurance type, histology, or smoking status at diagnosis.
Abstract 1141: LPA stimulates glycolytic shift of ovarian cancer cells via gip2 oncogenes
Authors: Ji Hee Ha, Rangasudhagar Radhakrishnan, Danny Dhanasekaran
Journal: Cancer Research (2015)

Abstract Ovarian cancer patients show increased levels of lysophosphatidic acid (LPA) in their serum and ascitic fluid. Our previous studies have established a critical role for LPA in inducing proliferation as well as migration of ovarian cancer cells. In the present study, we focused on identifying novel therapeutic targets in the oncogenic signaling pathway regulated by LPA. Using a commercial pathway reporter array of 45 transcription factors, we found that hypoxia-induced factor-1 alpha (HIF-1 alpha) was the most activated transcription factor induced by LPA. Both stable as well as transient silencing of Galphai2, a downstream signaling mediator for LPA, abrogates LPA induced increase in HIF-1 alpha expression. In addition, our results indicate that LPA stimulated an increase in the expression of Hexokinase-2 (HK2) and Glucose transporter 1 (GLUT1), which are targets of HIF-1 alpha, are also mediated via Galphai2 signaling pathway. To determine the outcome LPA induced increase in HK2 and GLUT1 on glycolytic rates, we measured the extracellular acidification rate (ECAR) in ovarian cancer cells following treatment with LPA, using an XFe analyzer. In both SKOV3-ip and OVCA429 cells, LPA increased ECAR in a dose-dependent manner. Silencing Galphai2 as well as HIF-1 alpha in ovarian cancer cells reduced ECAR indicative of reduced glycolytic rate. The current study, points to the identification of LPA(R)-Galphai2-HIF-1 alpha-GLUT1 signaling axis as potential metabolism-targets in ovarian cancer treatment. Citation Format: Ji Hee Ha, Rangasudhagar Radhakrishnan, Danny Dhanasekaran. LPA stimulates glycolytic shift of ovarian cancer cells via gip2 oncogenes. [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 1141. doi:10.1158/1538-7445.AM2015-1141
MECp, a Salvage Regimen with Drugs Not Employed as Frontline Therapy, Allowed to Obtain a High CR Rate and to Bring to Unrelated Allogeneic Transplantation a High Proportion of Adult Patients with Relapsed ALL.
Authors: Erika Borlenghi, Elisa Cerqui, Chiara Cattaneo, Francesco Zuccalà, Piero Galbiati, Liliana Baushi, Mariella D'Adda, Giuseppe Rossi
Journal: Blood (2009)
458. Sensitizing Ovarian Cancer Cells To Chemotherapy By Interfering With Pathways That Are Involved in the Formation and Maintenance of Cancer Stem Cells
Authors: Kamola Saydaminova, Robert Strauss, Min Xie, Charles Dreshner, Sheng Ding, Andre Lieber
Journal: Molecular Therapy (2015)

It has been suggested that tumor re-growth, as well as chemotherapy resistance and metastasis, are dependent on a small sub-population of cancer cells within the tumor that are thought to represent cancer stem cells (CSCs), i.e. self-renewing cells with pluripotent potential and tumor forming ability. We and others have shown that putative ovarian CSCs are in a transitional phase between epithelial and mesenchymal cell stages and that considerable plasticity exists between non-CSCs and CSCs. These transitions are based on epigenetic changes involving either epithelial-to-mesenchymal transition (EMT) or the reverse process mesenchymal-to-epithelial transition (MET). Here we report that primary ovarian cancer cells treated with the chemotherapeutic drug cisplatin undergo partial EMT/MET-like changes in culture and in xenograft tumors. Concurrently with the induction of partial EMT/MET, cisplatin treatment of primary ovarian cancer cells enriched for CSCs that were positive for the stem cell markers Nanog, Oct4, and Sox2, indicating that the formation of CSC involves partial EMT/MET-like events. In vivo cisplatin treatment of mice with xenograft tumors showed an increase in Nanog and E-cadherin expression as well as in MAPK signaling. Notably, MET initiates and is required for the nuclear reprogramming of fibroblasts into induced pluripotent stem (iPS) cells indicating similarities in the formation of iPS cells and CSCs. We therefore screened 30 compounds from a library of small molecules, which has previously been generated to study EMT/MET signaling in iPS cells. We identified compounds (e.g. compound GHDM1516) that blocked EMT and the formation of CSCs in primary ovarian cancer cultures. Co-treatment of cancer cells with GHDM1516 significantly increased cisplatin induced apoptosis/necrosis in CSCs as assessed by flow cytometry for Annexin V/7-AAD. In contrast, compounds that promoted MET (e.g. compound SD83) acted synergistically with cisplatin and increased the number of CSCs and cisplatin-resistant cancer cells. We are currently performing in vivo studies with a combination GHDM1516 and cisplatin in xenograft models of ovarian cancer. Furthermore, a "wound healing", functional EMT assays showed the EMT inhibitory potential of GHDM1516 after treatment of ovarian cancer cells with other chemotherapy drugs such as Paclitaxel and Etoposide. Our findings suggest that similarities in iPS and CSC formation can be exploited to find new cancer treatments that are targeted towards CSCs. Our data indicate that it might be possible to sensitize late stage tumors to chemotherapy by interfering with pathways that are involved in the formation and maintenance of CSCs.
Abstract A85: Metabolic wiring dictates GOT1 dependency in pancreatic cancer
Authors: Costas A. Lyssiotis
Journal: Cancer Research (2016)

Abstract Pancreatic Ductal Adenocarcinoma (PDA) is an extremely aggressive disease. The 5-year survival rate is a shockingly low 8%, a number that has hardly increased in the last 30 years. This owes in large part to the fact that effective treatment options for PDA do not exist. A hallmark of pancreatic cancers, and one that contributes to this resistance, is the metabolic environments that they create locally and systemically. Pancreatic tumors exist in a highly inflammatory environment, are under severe physical and oxidative stress, and do not have functional vasculature to deliver oxygen and nutrients. Despite these unfavorable circumstances for growth, these tumors thrive. Clearly metabolism is rewired in unique ways to facilitate survival and growth in this unusual and hostile environment. Based on this framework, we have been mapping the metabolic pathways in PDA to identify aspects of metabolism that are unique or highly over-utilized. Previously, we defined a novel pathway used by PDA cells to maintain redox balance via NADPH generation. Inhibition of a central enzyme in this pathway, cytosolic aspartate aminotransferase (GOT1), dramatically impairs growth in vitro and in vivo. Importantly, these effects can be completely reversed by supplying PDA cells with antioxidants. We also found that this pathway is regulated by mutant KRAS in PDA and, accordingly, non-transformed pancreatic epithelial cells are unresponsive to GOT1 inhibition. Subsequently, we interrogated GOT1 dependence in another KRAS transformed cancer, colon cancer, and found that they, like non-transformed cells, do not respond to GOT1 inhibition. Through a detailed series of metabolomics and functional assays, we ultimately found that colon cancers bypass GOT1 dependence favoring flux through ATP citrate lyase (ACL), a mechanism dictated not at the transcriptional level but by the metabolic wiring in these cells. Furthermore, ACL knockdown dramatically sensitizes colon cancer cells to GOT1 inhibition mediated redox and growth defects. In addition to revealing novel aspects of tissue specific metabolic pathway regulation, this analysis also illustrated novel metabolic dependencies that can be exploited for therapeutic gain. Citation Format: Costas A. Lyssiotis.{Authors}. Metabolic wiring dictates GOT1 dependency in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A85.
Cellular p16 localization and survival outcomes in head and neck cancer.
Authors: D. N. Hayes, N. Zhao, M. Ang, M. Patel, M. D. Wilkerson, X. Yin, M. C. Hayward, W. K. Funkhouser, A. Olshan
Journal: Journal of Clinical Oncology (2011)

5572 Background: Head and neck squamous cell carcinoma (HNSCC) constitutes approximately 3-5 percent of all cancers. Recent data suggest an increasing incidence rate among younger people who are often non-smokers and non-drinkers, which are believed to be caused by human papillomavirus (HPV) infection. HPV positive tumors are typically found in the oropharynx and have better response to treatment and better disease outcome despite more advanced nodal stages. Therefore, HPV-positive HNSCCs represent a unique clinical subgroup with a separate tumor entity. Methods: Patients treated for HNSCC from 2002 to 2006 at UNC hospitals and had banked tissue available were eligible for this study. Tissue microarrays (TMA) were generated in triplicate. Immunohistochemical (IHC) staining for p16 was performed and scored separately for nuclear staining and cytoplasmic staining. Human papilloma virus (HPV) staining was also carried out using monoclonal antibody E6H4. P16 expression, HPV status and other clinical features were correlated with progression-free (PFS) and overall survival (OS). Results: 135 patients had sufficient sample for this analysis. Median age of diagnosis was 57 years (range 20-82), with 68.9% males, 8.9% never smokers and 32.6 % never drinkers. 3 year OS rate and PFS rate was 63.0% and 54.1% respectively. Based on the p16 staining score, patients were divided into three groups: high nuclear any cytoplasmic staining group (HNAC), low nuclear low cytoplasmic staining group (LNLC) and low nuclear high cytoplasmic staining group (LNHC). HNAC and LNLC groups had significantly better overall survival than LNHC groups with hazard ratios of 0.01 and 0.37 respectively, after controlling for other factors, including HPV status. HNAC and LNLC groups also had better progression-free survival than LNHC group, although not significantly. A similar trend was observed in an independent patient population with comparable magnitude of effect. Conclusions: Different p16 protein localization suggested different survival outcomes: high nuclear p16 staining is an indication of better survival while high cytoplasmic p16 staining signals poor survival outcome; and this effect is beyond the effect of HPV infection.
Ebola vaccine is highly protective, show latest study results
Authors: Zosia Kmietowicz
Journal: BMJ (2016)

Scientists have said that they will be prepared with an effective vaccine should Ebola emerge in a new outbreak, after trial results showed high protection against the disease.

No cases were shown among the 5837 people who received the vaccine, called rVSV-ZEBOV, in a 2015 trial carried out in Guinea, whereas 10 days or more after vaccination 23 cases were reported among 6004 people who did not receive the vaccine, showed the results, published in the Lancet .1

The findings add weight to early results of the trial published last year, which showed that none of the contacts of someone who had contracted the disease and who were vaccinated immediately became infected.2

The trial was led …
Controllably Switched Drug Release from Successively Dual‐Targeted Nanoreservoirs
Authors: Zhaomin Tang, Yuqian Gao, Dan Li, Shaobing Zhou
Journal: Advanced Healthcare Materials (2016)

The development of a nanocarrier with a capacity of releasing therapeutic agent "on demand" is of great importance for enhancing drug efficacy and reducing its side effect. Here, a multifunctional mesoporous silica nanoparticle is presented for cancer therapy. This nanoparticle can not only successively target tumor tissue and tumor cells but also has a function of controllably switching the drug release. Low molecular weight poly(ethyleneimine) segments, which are decorated on the surface of magnetic mesoporous silica nanoparticle with disulfide bonds, are chemically cross-linked, leading to the mesopores being "closed" in blood circulation but being "open" via taking off the coating in cytoplasm. As a result, the encapsulated drug can be kept in nanoparticles in the normal conditions, while be rapidly released in a reduction condition. In vivo antitumor activity demonstrates that this nanoparticle has the highest safety to body and the best therapeutic efficacy against tumors. Therefore, this work presents a good example of rational design of nanocarriers for highly effective cancer therapy.
Classification of Childhood Bone Marrow Failure Syndrome Based On Revised WHO Classification.
Authors: Asahito Hama, Ayami Yoshimi, Shinsuke Hirabayashi, Hideki Muramatsu, Nobuhiro Nishio, Toshihito Nagata, Yoshiyuki Takahashi, Masahiro Tsuchida, Masafumi Ito, Atsushi Manabe, Akira Ohara, Seiji Kojima
Journal: Blood (2009)
Effects of omeprazole or pantoprazole on platelet function in non-ST-segment elevation acute coronary syndrome patients receiving clopidogrel
Authors: Ruo-Xi Gu, Xiao-Zeng Wang, Jing Li, Jie Deng, Xing-Xing Li, Jiao Wang
Journal: Military Medical Research (2016)

This study evaluated the effect of omeprazole or pantoprazole on platelet reactivity in non-ST-segment elevation acute coronary syndrome (NSTE-ACS) patients receiving clopidogrel.Consecutive patients with NSTE-ACS (n = 620) from general hospital of Shenyang Military Command were randomized to the omeprazole or pantoprazole (20 mg/d) group (1:1), and received routine dual antiplatelet treatment. Patients' reversion rate of adenosine diphosphate-induced platelet aggregation (ADP-PA) was assessed at baseline, 12 to 24 h after administration of medication, and after 72 h of percutaneous coronary intervention (PCI). The primary endpoint of the study was platelet reactivity assessed with ADP-PA at 30 days after PCI. Adverse events (AEs) were recorded for 30-day and 180-day follow-up periods.There were no significant differences between both the groups in platelet response to clopidogrel at 12-24 h after drug administration (54.09% ± 18.90% vs 51.62% ± 19.85%, P = 0.12), 72 h after PCI (52.15% ± 19.45% vs 49.66% ± 20.05%, P = 0.18), and 30 days after PCI (50.44% ± 14.54% vs 48.52% ± 15.08%, P = 0.17). The rate of AEs did not differ significantly between groups during the 30-day (15.2% vs 14.8%, P = 0.91) and 180-day (16.5% vs 14.5%, P = 0.50) follow-up periods after PCI.The addition of omeprazole or pantoprazole to clopidogrel did not restrict the effect of platelet aggregation by reducing the conversion of clopidogrel. Compared with clopidogrel alone, pantoprazole-clopidogrel and omeprazole-clopidogrel combinations did not increase the incidence of adverse clinical events during 30-day and 180-day follow-up periods after PCI.The study is registered in the National Institutes of Health website with identifier NCT01735227. Registered 14 November 2012.
Randomized controlled trial comparing 35% trichloroacetic acid peel and 5-aminolaevulinic acid photodynamic therapy for treating multiple actinic keratosis
Authors: G. Holzer, A. Pinkowicz, S. Radakovic, J.B. Schmidt, A. Tanew
Journal: British Journal of Dermatology (2016)

Photodynamic therapy (PDT) and chemical peels with trichloroacetic acid (TCA) can be applied to large skin areas and thus are suitable treatment options for patients with multiple actinic keratosis (AK). However, despite its long use, TCA has been investigated only rarely in this indication. This randomized, observer‐blinded, intrapatient comparative study sought to investigate the efficacy and safety of 35% TCA vs. aminolaevulinic acid 20% (ALA) PDT in patients with extensive field cancerization and multiple AKs in the face or on the scalp. Twenty‐eight patients with at least five AKs in two comparable anatomical areas on the head were treated with 35% TCA and ALA PDT randomly assigned to each area. Their therapeutic efficacy, adverse events and cosmetic outcome were assessed by a blinded investigator at 1, 3, 6 and 12 months after treatment. After 12‐months' follow‐up TCA and ALA PDT reduced the total lesion count, the primary outcome, by 31% and 58%, respectively (P =0·006). Complete clearance of pre‐existing AKs were 49% for TCA and 74% for ALA PDT (P =0·011). Treatment failure (number of AKs greater than 50% of the baseline count) was observed in seven patients (25%) after TCA and in two patients (7%) after PDT treatment. Treatment‐related pain was significantly higher for ALA PDT (visual analogue scale 7·5 ± 2·3 vs. TCA: 5·1 ± 2·6; P =0·04), whereas scarring (n = 6, 21%) was seen only in TCA treated patients. ALA PDT provided better clinical results than TCA in the treatment of patients with extensive field cancerization and multiple AKs.
Prevalence and correlates of suicidal ideation among outpatients at a comprehensive cancer center.
Authors: J. M. Randall, L. Bazhenova, M. White, A. A. Bharne, K. A. Shimabukuro, Y. Matusov, K. Messer, A. Lowery, M. Loscalzo, K. Clark, W. Bardwell
Journal: Journal of Clinical Oncology (2011)

9044 Background: Suicide is a tragic and preventable cause of death among cancer patients. We examined prevalence and correlates of suicidal ideation (SI) in a series of patients with and without cancer at the UCSD Moores Comprehensive Cancer Center (MCCC). Methods: During initial consultations, patients at MCCC complete a 39-item survey assessing potential problems, including pain and mood disturbance, on a 5-point scale (0=not a problem, 1=mild problem, 2=moderate problem, 3=severe problem, 4=very severe problem). We report prevalence of SI, specifically, “Thoughts of ending my own life,” from 1,883 consecutive patients, 1,473 with cancer, and 410 without a cancer diagnosis. Results: Overall, 101 of 1883 (5.36%) patients endorsed SI. Sixty-seven patients rated the problem as mild (3.56%), 21 moderate (1.12%), 3 severe (0.16%), and 10 very severe (0.53%). Eighty-six out of 1,473 (5.84%) cancer patients endorsed SI, as compared to 15 out of 410 (3.6%) non-cancer patients (p = 0.08). SI was endorsed by 6.87% of men and 4.71% of women, nearing significant difference (p = 0.06). Patients age <30 years (1.75%) were significantly less likely to endorse SI than patients age ≥ 30 years (6.24%, p = 0.02). Marital status was not associated with the prevalence of SI (p = 0.46). Depression and pain were associated with the presence of SI (both p < 0.01). Ninety-three of 767 (12.1%) patients who endorsed depression as a problem also endorsed SI, as did 79 of 757 (10.4%) patients who reported pain. Of note, 49 of 269 (18.2%) patients “needing practical help at home” endorsed SI, compared to 44 of 1,293 patients who did not (p < 0.01). Additionally, 59 of 376 (15.6%) patients who noted a problem “being able to care for myself” endorsed SI, compared to 39 of 1,192 who reported no problem with self-care (p < 0.01). All p-values were calculated using Fisher’s exact test. Conclusions: SI is prevalent among outpatients at a comprehensive cancer center and particularly those >30 years old. The presence of pain and depression are associated with SI. Loss of autonomy and need of practical help at home are also strongly associated with SI. Clinicians should be especially mindful of SI in patients who are depressed, in pain, losing autonomy, and/or socially isolated.