tbuckley/cabot-search huggingface dataset:
Prospective study of fatigue and metabolic parameters in patients with early breast cancer (EBC) receiving concomitant radiotherapy and anthracycline-based adjuvant chemotherapy
Authors: J. de Grève, C. Fontaine, K. Torosian, A. Meulemans, L. de Meirleir, E. Gerlo, K. von Kemp, P. Goyens, A. de Waele
Journal: Journal of Clinical Oncology (2005)

852 Background: Fatigue affects the quality of life of cancer patients. Treatment and disease related factors contribute to the symptom. The metabolic factors involved have not been studied adequately in humans. We have initiated a clinical-metabolic study of the effect of adjuvant chemotherapy on fatigue, excluding confounding disease-related factors. The hypothesis was that chemotherapy affects mitochondrial energy production. Methods: Patients were treated with 6 cycles of adjuvant CEF, concurrent with locoregional radiotherapy. Consenting patients were prospectively followed with the FACT-F subscale; an standardized aerobic forearm exercise test with measurement of blood levels of lactate, pyruvate, pH, free carnitine and acylcarnitines, pO2, pCO2, urinary organic acids and arterial flow. All measurements were performed at baseline, after 3 and 6 cycles of chemotherapy, and 3 and 6 months of follow-up. The variables were determined at rest, during exercise and in the recovery phase. Results: Seventeen patients were included, 12 patients are currently evaluable after 3 cycles of chemotherapy. Mean age was 53 years (39–65 years). At baseline the FACT-F subscale was less than 32 in two patients whom were considered severely fatigued. At test 2, two more felt severe fatigue. The mean fatigue subscale score at baseline was 37(4–49), whereas after 3 cycles of chemotherapy the score decreased at 33 (6–46). This is a clinically important difference. Tissue extraction of O2 and arterial blood flow were not affected. Mean free carnitine levels were supernormal at baseline and decreased by 33%; acylcarnitines decreased by 22% after cycle 3. Conclusions: This is the first prospective study to demonstrate a clinically significant decline in the fatigue subscale under adjuvant anthracycline-based chemotherapy in early breast cancer. The results suggest that oxidative phosphorylation is not significantly affected but that a chemotherapy-induced decrease in carnitine levels might be responsible for the fatigue symptoms. No significant financial relationships to disclose.
Deacetylase Inhibitor Cocktails Provide Striking Synergistic Interactions in Human Leukemia Cells.
Authors: Michele Cea, Antonia Cagnetta, Floriana Fruscione, Santina Bruzzone, Gabriele Zoppoli, Anna Garuti, Eva Moran, Valentina Grillo, Fabio Ferrando, Salvatore Casciaro, Ivana Pierri, Marco Gobbi, Alberto Ballestrero, Franco Patrone, Alessio Nencioni
Journal: Blood (2009)
Unauthorized Online Sales of Secondhand Continuous Positive Airway Pressure Devices
Authors: Marisa I. Peine, J. Roxanne Prichard, Ken M. Kunisaki
Journal: JAMA Internal Medicine (2016)

Unauthorized Online Sales of Secondhand Continuous Positive Airway Pressure DevicesContinuous positive airway pressure (CPAP) devices are used to treat obstructive sleep apnea and can improve patients' blood pressure, reaction times while driving, and quality of life. 1 Health insurance generally covers CPAP devices, but the typical cost of $600 to $2000 for patients without insurance or with minimal coverage can be prohibitive. 2 In the United States, CPAP devices require a prescription for purchase.According to the US Food and Drug Administration, CPAP devices are Class II medical devices with possible risks. 3 Although the US Food and Drug Administration does not authorize sales of secondhand CPAP devices, such devices are bought and sold by private individuals.
A phase I, first-in-human study of argx-111, a monoclonal antibody targeting c-met in patients with solid tumors.
Authors: Philippe G. Aftimos, Philippe Barthelemy, Christian D. Rolfo, Valerie Hanssens, Natalie De Jonge, Karen Silence, Torsten Dreier, Hans de Haard, Marc Peeters, Alain Thibault, Ahmad Awada
Journal: Journal of Clinical Oncology (2015)

2580 Background: Dysregulation of the tyrosine kinase receptor c-Met, is associated with tumorigenesis, metastasis and progression via hepatocyte growth factor (HGF)-dependent or-independent mechanisms. Methods: ARGX-111, a monoclonal IgG1 SIMPLE Antibody glyco-engineered for enhanced ADCC properties (POTELLIGENT), is currently being investigated in a Phase 1 clinical trial (accelerated titration design) in patients with advanced solid tumors (NCT 02055066). Results: As of January 2015, 16 patients (median age: 59 years; prior chemotherapy/targeted therapies/biological therapies: 81%/44%/31%;) with tumors staining positive (> 50% of tumor cells) for c-Met by immunohistochemistry have been treated at 4 dose levels (0.3, 1, 3, and 10 mg/kg IV q3 weeks; n = 2, 2, 9, and 3, respectively) and received a total of 41 cycles (median = 2; range 1-9). Patients with different histologies were enrolled (5 upper GI, 3 RCC, 2 pancreas, 2 NSCLC, 2 cervix and 2 others). The most common drug-related adverse events (AE) were: infusion-related reaction (IRR) (56%), fatigue (38%) and diarrhea (25%). Drug-related Grade 3 AEs (IRRs) were observed in 2 patients. The MTD was 3 mg/kg IV q3 weeks. Pharmacokinetics were dose-linear, with a half-life of 3-4 days. Serum HGF levels remained stable during treatment. Ex vivoADCC and depletion of circulating c-Met+ cells were observed in all patients and NK cell counts remained stable during treatment across all dose levels. One patient with metastatic, c-Met amplified gastric cancer refractory to platinum and taxane-based chemotherapy regimens, was treated at 0.3 mg/kg (escalated to 1.0 mg/kg) and maintained stable disease by RECIST for 6 months, associated with mixed metabolic response on PET scan, and a more than 50% reduction in CTCs. Conclusions: Recruitment of the safety expansion cohort is ongoing. Full results will be presented at the meeting. Clinical trial information: NCT 02055066. Dose 0.3 mg/kg 1 mg/kg 3 mg/kg 10 mg/kg Cmax(mean) (µg/ml) 5.6 11.4 43.4 113.2 ADA No No No No HGF levels Stable Stable Stable ND ADCC Yes Yes Yes Yes NK-cell count Stable Stable Stable Stable
Identifying components for programmatic latent tuberculosis infection control in the European Union
Authors: Andreas Sandgren, Jannigje M Vonk Noordegraaf-Schouten, Anouk M Oordt-Speets, Gerarda B van Kessel, Sake J de Vlas, Marieke J van der Werf
Journal: Eurosurveillance (2016)

Individuals with latent tuberculosis infection (LTBI) are the reservoir of Mycobacterium tuberculosis in a population and as long as this reservoir exists, elimination of tuberculosis (TB) will not be feasible. In 2013, the European Centre for Disease Prevention and Control (ECDC) started an assessment of benefits and risks of introducing programmatic LTBI control, with the aim of providing guidance on how to incorporate LTBI control into national TB strategies in European Union/European Economic Area (EU/EEA) Member States and candidate countries. In a first step, experts from the Member States, candidate countries, and international and national organisations were consulted on the components of programmatic LTBI control that should be considered and evaluated in literature reviews, mathematical models and cost-effectiveness studies. This was done through a questionnaire and two interactive discussion rounds. The main components identified were identification and targeting of risk groups, determinants of LTBI and progression to active TB, optimal diagnostic tests for LTBI, effective preventive treatment regimens, and to explore the potential for combining LTBI control with other health programmes. Political commitment, a solid healthcare infrastructure, and favourable economic situation in specific countries were identified as essential to facilitate the implementation of programmatic LTBI control.
Optimizing Treatment for Elderly Patients With Newly Diagnosed Multiple Myeloma: A Personalized Approach
Authors: Alessandra Larocca, Antonio Palumbo
Journal: Journal of Clinical Oncology (2016)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice. An 84-year-old woman presented with bone pain and lytic bone lesions in April 2010. Diagnosis of multiple myeloma was based on the presence of an immunoglobulin G lambda serum M protein (4,784 mg/dL) and confirmed by the findings of bone marrow plasma cell infiltration, with t(11;14) chromosomal abnormality detected by fluorescence in situ hybridization analysis. The patient's medical history was significant for hypertension; she had an Eastern Cooperative Oncology Group performance status of 1, International Staging System (ISS) stage of 1, and Durie-Salmon stage of IIIA. In May 2010, the patient was enrolled in a randomized phase III trial comparing different lenalidomide-based treatments and received induction with lenalidomide plus dexamethasone (nine cycles) followed by lenalidomide maintenance. The patient started treatment with lenalidomide 25 mg per day for 21 days and reduced-dose dexamethasone 20 mg per week per protocol because of age. Induction was well tolerated; no relevant complications occurred, except for grade 1 fatigue and grade 1 diarrhea. Best response was partial response. In March 2011, she started maintenance with lenalidomide 10 mg per day. A dose reduction of lenalidomide 5 mg per day was required because of grade 2 diarrhea. In July 2015, the patient experienced relapse, with painful collapse of L3 vertebral body.
Mortality trends and differentials in South Africa from 1997 to 2012: second National Burden of Disease Study
Authors: Victoria Pillay-van Wyk, William Msemburi, Ria Laubscher, Rob E Dorrington, Pam Groenewald, Tracy Glass, Beatrice Nojilana, Jané D Joubert, Richard Matzopoulos, Megan Prinsloo, Nadine Nannan, Nomonde Gwebushe, Theo Vos, Nontuthuzelo Somdyala, Nomfuneko Sithole, Ian Neethling, Edward Nicol, Anastasia Rossouw, Debbie Bradshaw
Journal: The Lancet Global Health (2016)

BackgroundThe poor health of South Africans is known to be associated with a quadruple disease burden. In the second National Burden of Disease (NBD) study, we aimed to analyse cause of death data for 1997–2012 and develop national, population group, and provincial estimates of the levels and causes of mortality.MethodWe used underlying cause of death data from death notifications for 1997–2012 obtained from Statistics South Africa. These data were adjusted for completeness using indirect demographic techniques for adults and comparison with survey and census estimates for child mortality. A regression approach was used to estimate misclassified HIV/AIDS deaths and so-called garbage codes were proportionally redistributed by age, sex, and population group population group (black African, Indian or Asian descent, white [European descent], and coloured [of mixed ancestry according to the preceding categories]). Injury deaths were estimated from additional data sources. Age-standardised death rates were calculated with mid-year population estimates and the WHO age standard. Institute of Health Metrics and Evaluation Global Burden of Disease (IHME GBD) estimates for South Africa were obtained from the IHME GHDx website for comparison.FindingsAll-cause age-standardised death rates increased rapidly since 1997, peaked in 2006 and then declined, driven by changes in HIV/AIDS. Mortality from tuberculosis, non-communicable diseases, and injuries decreased slightly. In 2012, HIV/AIDS caused the most deaths (29·1%) followed by cerebrovascular disease (7·5%) and lower respiratory infections (4·9%). All-cause age-standardised death rates were 1·7 times higher in the province with the highest death rate compared to the province with the lowest death rate, 2·2 times higher in black Africans compared to whites, and 1·4 times higher in males compared with females. Comparison with the IHME GBD estimates for South Africa revealed substantial differences for estimated deaths from all causes, particularly HIV/AIDS and interpersonal violence.InterpretationThis study shows the reversal of HIV/AIDS, non-communicable disease, and injury mortality trends in South Africa during the study period. Mortality differentials show the importance of social determinants, raise concerns about the quality of health services, and provide relevant information to policy makers for addressing inequalities. Differences between GBD estimates for South Africa and this study emphasise the need for more careful calibration of global models with local data.FundingSouth African Medical Research Council's Flagships Awards Project.
NRBP2 Overexpression Increases the Chemosensitivity of Hepatocellular Carcinoma Cells via Akt Signaling
Authors: Lixing Zhang, Chao Ge, Fangyu Zhao, Yang Zhang, Xin Wang, Ming Yao, Jinjun Li
Journal: Cancer Research (2016)

Abstract Hepatocellular carcinoma is highly resistant to chemotherapy. Research data supported that cancer stem cells (CSC) may be responsible for the chemoresistance and strategies that suppress CSCs stemness could also inhibit the drug resistance. In this study, we found that nuclear receptor binding protein 2 (NRBP2) expression was downregulated in the CD133+ hepatocellular carcinoma CSCs. Most adjacent noncancerous liver tissue analyzed expressed higher level of NRBP2 compared with cancerous tissue in hepatocellular carcinoma patients, and high NRBP2 expression indicated a better prognosis. Real-time PCR results showed that NRBP2 negatively correlated with stemness-related genes, including Oct3/4, Nanog, Notch1, Ep300, and CD133 mRNA expression. High NRBP2 expression in hepatocellular carcinoma cells downregulated CK19 protein expression, inhibited tumorsphere formation, and tumorigenesis ability, indicating that high NRBP2 expression restrains the hepatocellular carcinoma cell stemness. Overexpression of NRBP2 reduced the IC50 of sorafenib in hepatocellular carcinoma cells, and NRBP2 expression was negatively correlated with hepatocellular carcinoma cell resistance to the chemotherapy agents, including cisplatin and the Akt signaling inhibitor perifosine. Coimmunoprecipitation results showed that NRBP2 could bind with Annexin A2 (ANXA2) and inhibit ANXA2 expression. Coexpression of ANXA2 restored the chemoresistant ability in NRBP2-overexpressing hepatocellular carcinoma cells. Further analysis showed that NRBP2 downregulated Akt and its downstream signaling target Bad phosphorylation level. ANXA2 coexpression partially restored the Akt phosphorylation. Analysis of the expression of Bcl2 family proteins showed that NRBP2 may increase hepatocellular carcinoma cell chemosensitivity by regulating expression of survival proteins involved in the Akt and Bcl2 pathway. These results suggest that NRBP2 plays an important role in the tumor progression and chemotherapeutic resistance of hepatocellular carcinoma. Cancer Res; 76(23); 7059–71. ©2016 AACR.
Identifying the baseline: Oncologists’ understanding of cancer immunotherapy in metastatic melanoma.
Authors: Tara Herrmann, Suman Pearce, Haleh Kadkhoda, Sheryl L Konrad, Jeffrey S. Weber
Journal: Journal of Clinical Oncology (2015)

e20041 Background: Melanoma is a leading cause of cancer in the US. Although death rates from most types of cancer have decreased, death rates from melanoma have steadily increased in the last 2 decades. The objective of this study was to evaluate oncologists’ familiarity with cancer immunotherapy in the context of metastatic melanoma and the impact of education on narrowing gaps in clinical practice. Methods: An expert panel identified educational gaps in cancer immunotherapy. A series of 9 CME activities were developed, 3 of which focused on melanoma. Interactivity questions allowed learners to self-report their familiarity with immunotherapy concepts in the treatment of melanoma; case- and knowledge-based questions were constructed around evidence-based medicine. Confidentiality of respondents was maintained and responses de-identified and aggregated prior to analyses. Results: 2617 oncologists participated in the activities on melanoma. Oncologists reported a lack of familiarity with immunotherapies for the treatment of metastatic disease; less than 5% were very familiar. Upon completion of the education activities, there was an increase in the number of oncologists able to identify the role of immune checkpoint inhibitors in the adaptive immune response (44% at baseline to 55% post education, P < 0.05), mechanism of action for PD-1 inhibitors (81% vs 94%, P < 0.05), and a clinical response to cancer immunotherapies (43% vs 52%, P < 0.05). Improvement in detection of a patient’s clinical response was accompanied by a greater ability to differentiate irRC and RECIST criteria (70% vs 89%, P < 0.05). Despite improvements, several important gaps remained; understanding how immune checkpoints downregulate T cell responses, recognizing clinical responses, and comfort with managing side effects associated with use of cancer immunotherapies. Conclusions: Our study demonstrates the feasibility of targeted educational interventions for improving the knowledge and practice patterns of oncologists treating patients with \melanoma. Additional education is needed to maintain learning and continue to improve oncologists’ competence in the use of cancer immunotherapies in the management of metastatic melanoma.
Investigation of potential salivary biomarkers for the diagnosis of breast cancer.
Authors: Hiromitsu Jinno, Takeshi Murata, Makoto Sunamura, Masahiro Sugimoto
Journal: Journal of Clinical Oncology (2015)

145 Background: Saliva is an easily accessible and informative biological fluid which has high potential for the early diagnosis of diseases. Saliva-based diagnostics, particularly those based on metabolomics technology, offer a promising clinical strategy by characterizing the association between salivary analysts and a particular disease. The aim of this study is to investigate potential biomarkers in human saliva to facilitate the early diagnosis of breast cancer. Methods: We conducted a comprehensive metabolite analysis of saliva samples obtained from 60 breast cancer patients and 20 healthy controls, using capillary electrophoresis time-of-flight mass spectrometry (CE-TOF-MS). Statistical analyses were performed by using a nonparametric Mann-Whitney U test, multiple logistic regression and the receiver operating characteristics (ROC) to evaluate the predictive power of biomarkers. Results: Forty-nine patients (81.7 %) had invasive ductal carcinoma (IDC) and 9 patients (15.0 %) had ductal carcinoma in situ. In 33 patients receiving neoadjuvant treatment, saliva samples were obtained just before surgery. After removing the concomitantly observed peaks and noise peaks, an average of 205 peaks were derived from the metabolites. Among these peaks, five potential salivary biomarkers demonstrated significantly higher concentrations in breast cancer patients comparing with healthy individuals (p &lt; 0.05). Especially, salivary biomarkers obtained from patients with IDC before neoadjuvant treatments tended to be higher concentrations than those obtained after treatment. In these metabolites, the area under the ROC curves (AUCs) were 0.765 for substance A, 0.716 for substance B, 0.809 for substance C, 0.819 for substance D and 0.850 for substance E. Conclusions: Salivary metabolites are promising biomarkers for the early diagnosis of breast cancer.
Efficient Oncoretroviral Gene Transfer in Primary, Secondary and Tertiary NOD/SCID Mice under Serum-Free Conditions.
Authors: Loretta Gammaitoni, Simona Lucchi, Stefania Bruno, Melania Tesio, Monica Gunetti, Ymera Pignochino, Lorenza Lazzari, Massimo Aglietta, Paolo Rebulla, Wanda Piacibello
Journal: Blood (2004)
Bisphosphonate therapy in patients under androgen deprivation therapy for prostate cancer: A systematic review and meta-analysis.
Authors: M. L. Wroclawski, A. Serpa Neto, M. Tobias-Machado, M. A. Esteves, F. L. Fonseca, M. D. Senra, A. C. Pompeo, A. Del Giglio
Journal: Journal of Clinical Oncology (2010)

e15142 Background: Osteoporosis could be associated with the hormone therapy for metastatic prostate carcinoma (CaP) and with CaP per se. The objective of the study is to clarify the relationship between prostate cancer (under or not hormone therapy) and osteoporosis as well as the role of bisphosphonates in the treatment of this associated comorbidity. Methods: The Medline, Embase, Cancerlit, and American Society of Clinical Oncology Abstract databases were searched for published randomized, placebo-controlled trials evaluating the usage of bisphosphonates in patients with prostate cancer under androgen deprivation therapy. The outcomes assessed were: fracture, osteoporosis, osteopenia, the incidence of adverse events incidence and changes in bone mineral density (BMD) during the treatment. Results: Fifteen articles (2,634 participants) were included in the meta-analysis. Treatment with bisphosphonates showed a substantial effect in preventing fractures (RR, 0.80; p = 0.005) and osteoporosis (RR, 0.39; p < 0.00001). The zolendronate showed the best number needed to treat, compared with placebo, in relation to fractures and osteoporosis (NNT = 14.9 and 2.68, respectively). The between-group difference (bisphosphonates vs. placebo) in lumbar spine and femoral neck BMD were, respectively, 5.18 ± 3.38% and 2.35 ± 1.16%. This benefit of bone loss prevention could be reached without major side effects. Conclusions: Bisphosphonates are effective in preventing bone loss in patients with prostate cancer who are under androgen deprivation therapy. No significant financial relationships to disclose.