tbuckley/cabot-search huggingface dataset:
Phase I dose-ranging, pharmacokinetic (PK) study of tesetaxel, a novel orally active tubulin-binding agent.
Authors: M. Beeram, K. Papadopoulos, A. Patnaik, A. Qureshi, A. W. Tolcher
Journal: Journal of Clinical Oncology (2010)

e13075 Background: Currently approved taxanes are given intravenously and associated with marked hypersensitivity and cumulative neurotoxicity. Tesetaxel is a new orally active tubulin-binding agent in the taxane class with potent cytotoxic activity against numerous human cancer cell lines in vitro and in vivo. Activity is especially superior to FDA-approved taxanes in resistant cell lines that overexpress P- glycoprotein. Second-line therapy with tesetaxel (27-35 mg/m2 q3 weeks) in phase IIa studies produced response rates of 20% and 38% in taxane-naive patients (pts) with gastric and breast cancer, respectively. Neutropenia was the most common serious adverse event. We conducted a dose- ranging study to elucidate safety and PK at doses around a previously determined MTD (27 mg/m2) and to describe activity in taxane-refractory pts. Methods: Eligibility criteria included advanced solid tumors, ECOG PS ≤ 2, and adequate organ function. Tesetaxel was given for 2 cycles q3 weeks, with additional cycles available for non-progressive disease. A starting dose of 18 mg/m2 was escalated in increments of 3 mg/m2 to a maximum of 27 mg/m2. At least 3 pts were treated at each dose, with 12 treated at the MTD. Serial plasma samples were collected for analysis of parent drug and metabolites. Results: A total of 26 pts (9 men, 17 women; age 40-84 yrs) were enrolled; median number of prior systemic therapies was 4. Among 24 pts who completed tesetaxel therapy, 10 received 4 cycles (7 of whom continued therapy in an extension study), 10 received 2 cycles, and 4 stopped after Cycle 1 due to disease progression/lack of benefit. The MTD was 24 mg/m2; Grade 4 neutropenia for > 5 days or Grade 4 febrile neutropenia were dose limiting. No Grade 3-4 neurotoxicity occurred. In 24 pts with response assessment, a PR was achieved with 21 mg/m2 in 1 pt with nasopharyngeal adenocarcinoma. Stable disease was observed in 9 pts (several with progression on prior taxanes). PK analyses are ongoing. Conclusions: In heavily pretreated pts, we observed tesetaxel activity at doses as low as 21 mg/m2(a previously unstudied dose); therapy was generally well tolerated. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Genta Chemotherapy Foundation Genta
Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Risk Score in Young Adults Predicts Coronary Artery and Abdominal Aorta Calcium in Middle Age
Authors: Samuel S. Gidding, Jamal S. Rana, Christopher Prendergast, Henry McGill, J. Jeffery Carr, Kiang Liu, Laura A. Colangelo, Catherine M. Loria, Joao Lima, James G. Terry, Jared P. Reis, C. Alex McMahan
Journal: Circulation (2015)

Background— We explored whether, the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) coronary and abdominal risk scores measured at 18 to 30 years of age and changes in these scores would more strongly predict coronary artery calcium (CAC) and abdominal aortic calcium (AAC) assessed 25 years later, than scores measured 25 years later. Methods and Results— In the Coronary Artery Risk Development in Young Adults (CARDIA) study, 3008 participants had measurements of risk score components at 5-year intervals beginning at 18 to 30 years of age. CAC and AAC were assessed at 43 to 55 years of age. Odds ratios (ORs) for the presence and extent of CAC/AAC per/point higher score and c-statistics for predicting CAC/AAC were calculated. The prevalence of CAC was 28% and AAC was 53%. For each 1 point higher PDAY score, the odds of CAC were higher using baseline scores than year 25 scores (OR, 1.29; 95% confidence interval [CI], 1.25–1.33 versus OR, 1.12; 95% CI, 1.11–1.14). For AAC, ORs at years 0 and 25 were similar (OR, 1.29; 95% CI, 1.24–1.34 versus OR, 1.22; 95% CI, 1.19–1.26). C-statistic for CAC prediction was higher at year 0 than year 25 (0.731 versus 0.705) but similar at years 0 and 25 for AAC (0.665 versus 0.670). ORs for CAC were highest at baseline, and, for AAC, ORs were highest at year 10. Including change in PDAY scores with baseline scores improved prediction. Conclusions— Atherosclerosis risk and change in risk assessed in young adulthood years before subclinical atherosclerosis imaging provide strong prediction of future subclinical atherosclerosis. CAC and AAC reflect chronic risk exposure in addition to risk measured at the time of study.
THE DEVELOPMENT OF CURRENT CONCEPTS OF CATECHOLAMINE FORMATION
Authors: H. Blaschko
Journal: Pharmacological Reviews (1959)

We can today, with a fair degree of certainty, describe the main stages in the formation of the catecholamines. But many problems remain, e.g., that of the intimate nature of some of the intermediate chemical reactions and also that of the spatial relationship of the various stages and their correlation in the living cell. It must remain for the future to discover the nature of the intracellular signalling system, by which the storage site is told that amine is to be released, and also to study what we might call the adequate stimulus for re-synthesis.
A survey of nursing staff on intercostal drain (ICD) care in a tertiary centre
Authors: R. Naseer, R. Ahmed, A. Scott, M.E.J. Callister
Journal: European Respiratory Journal (2011)

Introduction: A recent audit of ICD's for pleural effusions in our 800 bedded tertiary centre revealed that in a 2 month period a significant proportion of drains were being managed on non respiratory wards (44% oncology & 16% other medical wards). Guidelines recommend that ICD's are nursed on wards familiar with drains and their management.

Method: We carried out an anonymised survey of nursing staff to enquire about training,knowledge & comfort in managing ICD's. The completed survey questionnaires were returned via internal mail.

Results: 110 questionnaires were distributed & 71 were returned (65%). 76% were Staff nurses, 22.5% Sisters & 1.5% were matrons. 77% had been qualified more than 3 years. 38% worked in general medicine, 20% in respiratory, 24% in Oncology & 18% in other specialities. A majority of the nurses felt they did not have adequate training, very few of them had any post registration training.

View this table:

Table 1. Summary of findings





Conclusion: There is a clear need need for education and training for nursing staff who are expected to look after patients with ICD'S. There is also a need for a trust wide chest drain observation chart.
ICAM-1-Targeted, Lcn2 siRNA-Encapsulating Liposomes are Potent Anti-angiogenic Agents for Triple Negative Breast Cancer
Authors: Peng Guo, Jiang Yang, Di Jia, Marsha A. Moses, Debra T. Auguste
Journal: Theranostics (2015)

Lipocalin 2 (Lcn2) is a promising therapeutic target as well as a potential diagnostic biomarker for breast cancer.It has been previously shown to promote breast cancer progression by inducing the epithelial to mesenchymal transition in breast cancer cells as well as by enhancing angiogenesis.Lcn2 levels in urine and tissue samples of breast cancer patients has also been correlated with breast cancer status and poor patient prognosis.In this study, we have engineered a novel liposomal small interfering RNA (siRNA) delivery system to target triple negative breast cancer (TNBC) via a recently identified molecular target, intercellular adhesion molecule-1 (ICAM-1).This ICAM-1-targeted, Lcn2 siRNA-encapsulating liposome (ICAM-Lcn2-LP) binds human TNBC MDA-MB-231cells significantly stronger than non-neoplastic MCF-10A cells.Efficient Lcn2 knockdown by ICAM-Lcn2-LPs led to a significant reduction in the production of vascular endothelial growth factor (VEGF) from MDA-MB-231 cells, which, in turn, led to reduced angiogenesis both in vitro and in vivo.Angiogenesis (neovascularization) is a requirement for solid tumor growth and progression, and its inhibition is an important therapeutic strategy for human cancers.Our results indicate that a tumor-specific strategy such as the TNBC-targeted, anti-angiogenic therapeutic approach developed here, may be clinically useful in inhibiting TNBC progression.
Second test for Down’s syndrome is recommended for NHS
Authors: Jacqui Wise
Journal: BMJ (2016)

A second, non-invasive test for Down’s syndrome has been recommended to form part of the fetal anomaly screening programme in England. If the government approves the change it will mean fewer women will need to undergo invasive diagnostic tests, which carry a small associated risk of miscarriage.

The UK National Screening Committee has recommended that non-invasive prenatal testing be offered as an additional test for Down’s syndrome and two other genetic conditions: Edward’s syndrome and Patau’s syndrome. Currently women between 10 and 14 weeks pregnant are offered screening for these genetic abnormalities through a combined test that comprises …
Invasive versus conservative strategy in patients aged 80 years or older with non-ST-elevation myocardial infarction or unstable angina pectoris (After Eighty study): an open-label randomised controlled trial
Authors: Nicolai Tegn, Michael Abdelnoor, Lars Aaberge, Knut Endresen, Pål Smith, Svend Aakhus, Erik Gjertsen, Ola Dahl-Hofseth, Anette Hylen Ranhoff, Lars Gullestad, Bjørn Bendz
Journal: The Lancet (2016)
Assessment of fluorinated steroids to avert progression and mortality in anti-SSA/Ro-associated cardiac injury limited to the fetal conduction system
Authors: Peter M Izmirly, Amit Saxena, Sara K Sahl, Ummara Shah, Deborah M Friedman, Mimi Y Kim, Jill P Buyon
Journal: Annals of the Rheumatic Diseases (2015)

Extension of disease beyond the atrioventricular (AV) node is associated with increased mortality in cardiac neonatal lupus (NL). Treatment of isolated heart block with fluorinated steroids to prevent disease progression has been considered but published data are limited and discordant regarding efficacy. This study evaluated whether fluorinated steroids given to manage isolated advanced block prevented development of disease beyond the AV node and conferred a survival benefit.In this retrospective study of cases enrolled in the Research Registry for NL, inclusion was restricted to anti-SSA/Ro-exposed cases presenting with isolated advanced heart block in utero who either received fluorinated steroids within 1 week of detection (N=71) or no treatment (N=85). Outcomes evaluated were: development of endocardial fibroelastosis, dilated cardiomyopathy and/or hydrops fetalis; mortality and pacemaker implantation.In Cox proportional hazards regression analyses, fluorinated steroids did not significantly prevent development of disease beyond the AV node (adjusted HR=0.90; 95% CI 0.43 to 1.85; p=0.77), reduce mortality (HR=1.63; 95% CI 0.43 to 6.14; p=0.47) or forestall/prevent pacemaker implantation (HR=0.87; 95% CI 0.57 to 1.33; p=0.53). No risk factors for development of disease beyond the AV node were identified.These data do not provide evidence to support the use of fluorinated steroids to prevent disease progression or death in cases presenting with isolated heart block.
Abstract 174: Weekly Variation in Out-of-Hospital Cardiac Arrests in a Nationwide Japanese Patient Population: Analysis of a Nationwide Population-Based Registry
Authors: Takehiro Tsukada, Takanori Ikeda, Takahiro Uechi, Hideki Nomura, Hideaki Yoshino, Takeaki Matsuda, Yoshihiro Yamaguchi, Naohiro Yonemoto, Hiroshi Nonogi, Takeshi Kimura, Ken Nagao
Journal: Circulation (2012)

Background: It is well known that acute cardiovascular events and sudden cardiac death occur most frequently in the morning. There are few reports about weekly variation recently. This study aimed ...
WITHDRAWN: The effects of liposomal hemoglobin-based artificial oxygen carriers (hemoglobin-vesicles) and red blood cells resuscitation on transfusion-related acute lung injury in hemorrhagic shock model rats
Authors: Masahiro Tokuno, Kazuaki Taguchi, Keishi Yamasaki, Hiromi Sakai, Masaki Otagiri
Journal: Asian Journal of Pharmaceutical Sciences (2015)

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at http://www.elsevier.com/locate/withdrawalpolicy.
Abstract 5556: Enhancing response of Ganoderma lucidum (Reishi) and lapatinib in HER2+ inflammatory breast cancer cells
Authors: Yismeilin Feliz-Mosquea, Ivette Suarez-Arroyo, Yaliz Loperena, Luis A. Cubano, Michelle M. Martinez-Montemayor
Journal: Cancer Research (2015)

Abstract Inflammatory Breast Cancer (IBC) is an aggressive and unique form of breast cancer that develops rapidly. IBC, like non-IBC breast cancers, is a heterogeneous disease and can occur as any of the six molecular breast cancer subtypes. However, they are most commonly either triple negative; that is presenting with an absence of estrogen receptor (ER-), progesterone receptor (PR-) and the epidermal growth factor receptor 2 (HER2-) or ER-, PR- and HER2+ overexpressed. There is no specific IBC treatment; thus, it seems possible to find a therapeutic for this deadly disease. Our published data demonstrates that Ganoderma lucidum (Reishi) inhibits the viability of the triple negative IBC SUM149 cell line, but not of MCF10A noncancerous mammary epithelial cells. Subsequently, in this study, we aimed to investigate Reishi effects in the viability and molecular signaling of the ER-, PR-, HER2+ IBC cell lines SUM190, KPL-4 and IBC-3. Furthermore, we studied the effects of Reishi on IBC cells when treated in complement with the HER2 Tyrosine Kinase Inhibitor, lapatinib. The hypothesis for this study is that Reishi inhibits cancer cell viability and sensitizes IBC cells to lapatinib therapy and downregulates key proteins overexpressed in IBC. Herein, SUM190, KPL-4 and IBC-3 cells were treated with increasing concentrations of lapatinib and/or Reishi for 24 or 72h. The combination of lapatinib plus Reishi reduced cell viability of KPL-4 cells to 80% when treated with a concentration of 0.25 mg/mL of Reishi for 72h. Additionally, our data shows a reduction in cell viability of 70% in SUM190 cells treated with lapatinib plus Reishi for 72h. Also, Reishi and lapatinib downregulate the expression HER2 in KPL-4 cell after 72h of treatment. Our results provide evidence that Reishi inhibits cancer cell viability, highlighting the potential of Reishi as a natural anti-IBC-therapeutic. This project was sponsored by NIH/NCI #1F31 CA174307 to ISA, Title V PPOHA US Department of Education #P031M105050 to UCC/LAC, NIH/RCMI #G12 MD007583 to UCC/MMM, NIH/INBRE #5P20 GM103475 to UPR/UCC/MMM, NIH/NIMHD U54 MD008149 UH/MMM. Citation Format: Yismeilin Feliz-Mosquea, Ivette Suarez-Arroyo, Yaliz Loperena, Luis A. Cubano, Michelle M. Martinez-Montemayor. Enhancing response of Ganoderma lucidum (Reishi) and lapatinib in HER2+ inflammatory 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 5556. doi:10.1158/1538-7445.AM2015-5556
Prognostic factors for favorable outcome in disseminated germ cell tumors.
Authors: R Birch, S Williams, A Cone, L Einhorn, P Roark, S Turner, F A Greco
Journal: Journal of Clinical Oncology (1986)

Between 1978 and 1982, 180 patients from Indiana University (Indianapolis) were entered on the Southeastern Cancer Study Group (SECSG) protocol 78 GU 240, a randomized comparison of cisplatin, vinblastine, and bleomycin (PVB) v PVB plus doxorubicin induction chemotherapy regimens, with a second randomization to maintenance vinblastine v no further therapy. One hundred forty-eight of these patients obtained a favorable response to chemotherapy, defined as a complete response (CR) or a surgical resection of teratoma. The prognostic significance of various patient characteristics was investigated using the logistic regression model. Two classifications for the extent of disease were considered: the Indiana staging system and the M.D. Anderson (MDA) staging system. The Indiana staging system had the greater prognostic significance. This staging system allowed the population to be split into three groups (minimal, moderate, advanced disease) in which the observed proportions of favorable responders were 99%, 90%, and 58%, respectively. Within the advanced group, the number of elevated tumor markers subdivided these patients into three groups, with the observed proportions of favorable responders being 73%, 65%, and 45%. The Indiana and MDA staging systems were subsequently prospectively used in SECSG protocol GU 81 332, a study randomizing patients to remission induction therapy with PVB v cisplatin, VP-16, and bleomycin. The prognostic value of the Indiana staging system was prospectively validated in this study.
Phase II study of paclitaxel in patients with recurrent malignant glioma.
Authors: M D Prados, S C Schold, A M Spence, M S Berger, L D McAllister, M P Mehta, M R Gilbert, D Fulton, J Kuhn, K Lamborn, D J Rector, S M Chang
Journal: Journal of Clinical Oncology (1996)

PURPOSE To assess the efficacy and toxicity of paclitaxel administered as a 3-hour infusion to patients with recurrent malignant glioma. PATIENTS AND METHODS Adult patients with recurrent malignant glioma following radiation therapy, who had received no more than one prior chemotherapy regimen and who had a Karnofsky performance status (KPS) &gt; or = 60, were treated with a 3-hour infusion of paclitaxel every 3 weeks. The initial dose was 210 mg/m2; dose escalation to 240 mg/m2 was allowed. Tumor response was assessed at 6-week intervals using radiographic and clinical criteria. Treatment was continued until documented tumor progression or a total of 12 paclitaxel infusions. RESULTS Of 41 eligible patients, all were assessable for treatment toxicity and 40 (98%) were assessable for response. The response rate (disease stabilization or better) was 35%. Twenty-nine patients (71%) underwent dose escalation to 240 mg/m2 without the use of growth factors. Toxicities included alopecia (98%), nausea (22%), arthralgias (32%), CNS toxicity (24%), peripheral neuropathy (15%), cardiac toxicity (7%), and myelosuppression (10% grade 3 or 4 hematologic toxicity). No patient developed febrile neutropenia. There was one allergic reaction (2%). CONCLUSION Paclitaxel is well tolerated at this dose schedule in patients with recurrent malignant glioma, and affords a modest response rate. Because minimal myelotoxicity was encountered in our patients, a dose-escalating phase I/II study of paclitaxel is planned to determine the maximal-tolerated dose (MTD).
Therapeutic Targeting of Raf-Induced Paradoxical Erk Activation with a Vertical Combination Hitting Multiple Steps Along the Mapk Cascade
Authors: U. Cesta Incani, A. Del Curatolo, I. Falcone, A. Eramo, G. Sette, I. Sperduti, S. Matteoni, S. Shirasawa, M. Broggini, R. De Maria, F. Cognetti, L. Ciuffreda, M. Milella
Journal: Annals of Oncology (2014)
A Trial of Two Questions
Authors: Tim Whelan
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.20.4135 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12377955 A Trial of Two Questions Tim WhelanxTim WhelanSearch for articles by this author Show More Cancer Care Ontario Hamilton Regional Cancer Center, McMaster University, Hamilton, Ontario, Canada https://doi.org/10.1200/JCO.2002.20.20.4135 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology
MiR-215 Is Induced Post-transcriptionally via HIF-Drosha Complex and Mediates Glioma-Initiating Cell Adaptation to Hypoxia by Targeting KDM1B
Authors: Jing Hu, Tao Sun, Hui Wang, Zhengxin Chen, Shuai Wang, Lifeng Yuan, Tingyu Liu, Hai-Ri Li, Pingping Wang, Yukuan Feng, Qinhong Wang, Roger E. McLendon, Allan H. Friedman, Stephen T. Keir, Darell D. Bigner, Jeff Rathmell, Xiang-dong Fu, Qi-Jing Li, Huibo Wang, Xiao-Fan Wang
Journal: Cancer Cell (2016)
Antitumor activity of 1, 4-bis (2'-chloroethyl)-l, 4-diazabicyclo-[2.2.1] heptane dimaleate (Dabis Maleate) in M5076 and its subline resistant to cyclophosphamide M5/CTX
Authors: G. Tagliabue, S. Filippeschi, H. Hendricks, M. D'lncalci
Journal: Annals of Oncology (1992)
Corrigendum re: “Percutaneous Nephrolithotomy Versus Retrograde Intrarenal Surgery: A Systematic Review and Meta-analysis” [Eur Urol 2015;67:125–37]
Authors: Shuba De, Riccardo Autorino, Fernando J. Kim, Homayoun Zargar, Humberto Laydner, Raffaele Balsamo, Fabio C. Torricelli, Carmine Di Palma, Wilson R. Molina, Manoj Monga, Marco De Sio
Journal: European Urology (2016)
Glioma-targeted therapy using Cilengitide nanoparticles combined with UTMD enhanced delivery
Authors: Ying-Zheng Zhao, Qian Lin, Ho Lun Wong, Xiao-Tong Shen, Wei Yang, He-Lin Xu, Kai-Li Mao, Fu-Rong Tian, Jing-Jing Yang, Jie Xu, Jian Xiao, Cui-Tao Lu
Journal: Journal of Controlled Release (2016)
Abstract 19037: Impact of Stress Hyperglycemia on Coronary Flow Reserve Following Successfully Recanalized Primary Acute Myocardial Infarction in Non-Diabetic Patients
Authors: Sari Imamura, Kumiko Hirata, Ikuko Teraguchi, takashi Yamano, takashi tanimoto, Yasushi Ino, Tomoyuki Yamaguchi, Takashi Kubo, Toshio Imanishi, Takashi Akasaka
Journal: Circulation (2013)

Background: Stress hyperglycemia (SH) is associated with adverse outcome and reduction in myocardial salvage after acute myocardial infarction (AMI), especially in non-diabetic patients. However, no relationship has been identified between admission blood glucose level and coronary flow reserve (CFR) as an index of microvascular function in non-diabetic patients with AMI. Methods: This study assessed 73 consecutive patients with a first anterior AMI who underwent successful percutaneous coronary intervention within 24 h from onset of symptoms. Plasma blood glucose was measured on admission. SH was defined as blood glucose ≥10 mmol/L (180 mg/dl). We excluded the patients with a previous or current diagnosis of diabetes or an abnormal oral glucose tolerance test (OGTT, 75-g) 5 days after admission. CFR was calculated as the ratio of hyperemic, which was induced by intravenous adenosine administration, to baseline diastolic coronary flow velocity of the left anterior descending artery using transthoracic echocardiography 7 days after AMI. Results: In 73 non-diabetic patients (mean age: 65 years, 48 males), 14 patients showed SH (218±48mg/dl). Baseline diastolic coronary flow velocity in patients with SH (24±11cm/s) was higher than those without SH(19±6 cm/s, p=0.04), while there was no significant difference in hyperemic coronary flow velocity between the patients with (50±26 cm/s) and without SH (48±20 cm/s). Calculated CFR of the patients with stress hyperglycemia (2.0±0.4) was significantly lower than those without stress hyperglycemia (2.4±0.6, p=0.02). Conclusions: CFR was impaired in non-diabetic patients with hyperglycemia on admission. Impaired coronary microcirculation may partly contribute to reduced myocardial salvage and adverse outcome in patients with SH.