tbuckley/cabot-search huggingface dataset:
Cannabinoids for Symptom Management and Cancer Therapy: The Evidence
Authors: Mellar P. Davis
Journal: Journal of the National Comprehensive Cancer Network (2016)

Cannabinoids bind not only to classical receptors (CB1 and CB2) but also to certain orphan receptors (GPR55 and GPR119), ion channels (transient receptor potential vanilloid), and peroxisome proliferator-activated receptors. Cannabinoids are known to modulate a multitude of monoamine receptors. Structurally, there are 3 groups of cannabinoids. Multiple studies, most of which are of moderate to low quality, demonstrate that tetrahydrocannabinol (THC) and oromucosal cannabinoid combinations of THC and cannabidiol (CBD) modestly reduce cancer pain. Dronabinol and nabilone are better antiemetics for chemotherapy-induced nausea and vomiting (CINV) than certain neuroleptics, but are not better than serotonin receptor antagonists in reducing delayed emesis, and cannabinoids have largely been superseded by neurokinin-1 receptor antagonists and olanzapine; both cannabinoids have been recommended for breakthrough nausea and vomiting among other antiemetics. Dronabinol is ineffective in ameliorating cancer anorexia but does improve associated cancer-related dysgeusia. Multiple cancers express cannabinoid receptors directly related to the degree of anaplasia and grade of tumor. Preclinical in vitro and in vivo studies suggest that cannabinoids may have anticancer activity. Paradoxically, cannabinoid receptor antagonists also have antitumor activity. There are few randomized smoked or vaporized cannabis trials in cancer on which to judge the benefits of these forms of cannabinoids on symptoms and the clinical course of cancer. Smoked cannabis has been found to contain Aspergillosis. Immunosuppressed patients should be advised of the risks of using "medical marijuana" in this regard.
Mutations in<i><scp>POGLUT</scp>1</i>in Galli–Galli/Dowling–Degos disease
Authors: N.J. Wilson, C. Cole, K. Kroboth, W.N. Hunter, J.A. Mann, W.H.I. McLean, K. Kernland Lang, H. Beltraminelli, R.A. Sabroe, N. Tiffin, G.J. Sobey, L. Borradori, E. Simpson, F.J.D. Smith
Journal: British Journal of Dermatology (2016)

The group of reticulate pigmentary disorders includes the rare autosomal dominant Dowling-Degos disease (DDD) and Galli-Galli disease (GGD;.OMIM 179850, OMIM 615327, OMIM 615696). 1 In light of substantial clinical, histological and mutational overlap between GGD and DDD they are considered to belong to the same entity. 2-3 Mutations in KRT5 (encoding keratin 5) have been associated with GGD/DDD since 2006. 2-5 With the development of whole exome sequencing (WES), mutations in POFUT1 (encoding protein O-fucosyltransferase 1) 6-7 and POGLUT1 (encoding protein O-glucosyltransferase 1) 8 have been shown to underlie some cases of GGD/DDD. We report mutations in POGLUT1 in 3 families of European ancestry.

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Isolated limb infusion chemotherapy with or without hemofiltration for recurrent limb melanoma
Authors: V. Casadei, S. Cecchini, D. Sarti, S. Ricci, S. Serresi, G. Ricotti, L. Mulazzani, P. Alessandroni, S. Luzi Fedeli, G. Fiorentini
Journal: Annals of Oncology (2015)
Abstract 42: A new type of drug resistance in cancer: extracellular ATP-induced resistance through ATP internalization and ATP-drug competition
Authors: Xuan Wang, Yunsheng Li, Yanrong Qian, Yanyang Cao, Xiaozhuo Chen
Journal: Cancer Research (2016)

Abstract Drug resistance is a major problem in cancer therapies and responsible for most relapse, one of the major causes of death in cancer. Several cancer drug resistance mechanisms are known, including genetic mutations in protooncogenes or tumor suppressor genes, cancer stem cells, and multi-drug resistance (MDR). Among these mechanisms, MDR is ATP-dependent. Intratumoral (extracellular) ATP levels of various cancer types are 10⁁3 to 10⁁4 times higher than those in their corresponding normal tissues but the biological significance of the high intratumoral ATP concentrations is unknown. We recently reported that extracellular ATP is internalized by cancer cells via macropinocytosis and enhances their growth and survival (1). Based on these results, we hypothesized that the internalized ATP also promotes drug resistance. Here we report that extracellular ATP, at concentrations in or below the range of reported intratumoral ATP levels, substantially increased intracellular ATP levels and promoted cancer cell drug resistance to tyrosine kinase inhibitor (TKI) sunitinib in human NSCLC A549 cells. The ATP increase and the drug resistance were mediated, at least in part, by macropinocytosis, clathrin- and caveolae-mediated endocytoses. The elevated intracellular ATP induced upregulated phosphorylation of PDGFR and proteins/enzymes in the PDGFR-mediated signaling pathways, such as Akt, mTOR, Raf and MEK, resulting in augmented cell growth and reduced apoptosis induced by sunitinib. The upregulated phosphorylation was not mediated by purinergic receptor signaling. Furthermore, in vitro, ex vivo, and in vivo, extracellular ATP partially restored phosphorylation levels of PDGRF and its downstream proteins/enzymes inhibited by sunitinib, a PDGFR inhibitor (TKI). These results strongly suggest that the extracellular ATP-increased intracellular ATP reversed the inhibition of TKIs by competing with the inhibitors for the ATP-binding site of PDGFR, enhancing the Akt-mTOR and Raf-MEK signaling pathways and promoting cancer cell survival. All these findings significantly expand our understanding of the roles of extracellular ATP in the Warburg effect (2) and drug resistance in cancer and indentify a new anti-drug resistance target. 1. Qian Y, Wang X, et al., Cancer Lett. 351(2014): 242-5. 2. Chen X, Qian Y, Wu S. Free. Radic. Biol. Med. 79(2015): 253-263. Citation Format: Xuan Wang, Yunsheng Li, Yanrong Qian, Yanyang Cao, Xiaozhuo Chen. A new type of drug resistance in cancer: extracellular ATP-induced resistance through ATP internalization and ATP-drug competition. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 42.
Abstract 3460: Breast and ovarian cancer prevention: is it time for population screening for BRCA mutations
Authors: Ian G. Campbell, Ella Thompson, Gillian Mitchell, Alison Trainer, Mary-Anne Young, Paul James
Journal: Cancer Research (2016)

Abstract Germline mutations in BRCA1 and BRCA2 confer high lifetime risk of breast and ovarian cancer but importantly these risks are not irreversible. Identification of asymptomatic carriers could significantly reduce the incidence of these diseases. The traditional model of familial breast and ovarian cancer practice involves ascertaining high-risk individuals based on family history. In general, the family is first identified because one member develops cancer and because of high-risk indicators, is referred to a Familial Cancer Centre. However, more than 50% of women who carry a BRCA1/2 mutation may not have a family history of cancer in a close relative. Momentum toward genetic screening of the asymptomatic population is growing but there remain some significant unknowns. For example it is unclear what is the true frequency of actionable mutations in the general western population and the extent to which the public would accept such screening, particularly for those individuals identified with an actionable mutation in the absence of an overt family history. As a first step toward population based BRCA gene screening, we are sequencing the entire coding region of 18 known and proposed HBOC genes in 4,000 cancer-free Australian women recruited from the lifepool study (www.lifepool.org), which is a cohort of women attending the Australian population, based mammographic screening program. To date, data from 1,997 women has identified 17 with actionable mutations in BRCA1 (4 mutations), BRCA2 (9 mutations) or PALB2 (4 mutations). All 17 women subsequently accepted an invitation to attend a Familial Cancer Centre and then proceeded to formal clinical genetic testing. In addition 4 women had pathogenic mutations in BRIP1. Our unique pilot data directly demonstrates a population carrier frequency of ∼1% for pathogenic mutations in these recognized high risk breast and/or ovarian cancer genes and that such testing is well accepted by the screened population. Citation Format: Ian G. Campbell, Ella Thompson, Gillian Mitchell, Alison Trainer, Mary-Anne Young, Paul James. Breast and ovarian cancer prevention: is it time for population screening for BRCA mutations. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3460.
Effect of enalapril, hydralazine plus isosorbide dinitrate, and prazosin on hospitalization in patients with chronic congestive heart failure
Authors: H. S. Loeb, G. Johnson, A. Henrick, R. Smith, J. Wilson, R. Cremo, J. N. Cohn
Journal: Circulation (1993)

Background. Hospitalization of persons with congestive heart failure for recurrent heart failure or other complications is common. Methods and Results. Male patients aged 18-75 with chronic heart failure were randomized in two sequential trials designed to study the efficacy of vasodilator therapy. Patients were evaluated every 3 months, and information regarding hospitalizations between visits was obtained from the patient, bis family, and/or hospital records. Hospitalization data also were obtained for patients who bad died between scheduled clinic visits. Hospitalizations were not recorded if a patient died during transit to the hospital or in the hospital emergency department before admission
Response to Rituximab Induction Is a Predictive Biomarker in Post-Transplant Lymphoproliferative Disorder (PTLD) and Allows Successful Treatment Stratification in an International Phase II Trial Including 152 Patients
Authors: Ralf Ulrich Trappe, Daan Dierickx, Heiner Zimmermann, Franck Morschhauser, Peter Mollee, Jan M Zaucha, Martin H. Dreyling, Ulrich Dührsen, Petra Reinke, Gregor Verhoef, Marion Subklewe, Andreas Hüttmann, Thomas Tousseyn, Gilles A. Salles, Volker Kliem, Corrado Tarella, Eric W Van Den Neste, Ingeborg A Hauser, Olivier Gheysens, Iannis Anagnostopoulos, Veronique Leblond, Hanno Riess, Sylvain Choquet
Journal: Blood (2015)
Profiling Myelodysplastic Syndromes By Mass Cytometry Demonstrates Distinct Immunophenotypic Aberrancies in Stem and Progenitor Populations
Authors: Gregory K. Behbehani, Rachel Finck, Nikolay Samusik, Pier Federico Gherardini, Kunju J Sridhar, Wendy J. Fantl, Peter L. Greenberg, Garry P. Nolan
Journal: Blood (2014)
Bariatric surgery and fractures
Authors: Marco Bueter
Journal: BMJ (2016)

Surgeons should consider assessing fracture risk in post-surgical patients

Obesity is escalating at an alarming rate globally and threatens healthcare systems worldwide. Although bariatric surgery has emerged as an effective treatment, and numbers of operations performed worldwide have risen sharply,1 many commentators still question surgical means to treat obesity. Scepticism has been fuelled by some evidence of negative long term effects including increased risks for nephrolithiasis and chronic kidney disease,2 relapse of type 2 diabetes mellitus,3 4 alcohol consumption,5 and suicide.6

Bariatric surgery may also have detrimental effects on bone health, indicated by a reduced bone mineral density postoperatively.7 8 9 10 However, whether this translates into a higher fracture risk is unclear.

The linked study by Rousseau and colleagues (doi:10.1136/bmj.i3794) aims to fill this gap in knowledge and evidence.11 The authors did a retrospective, nested case-control study including patients …
Abstract 3474: Prevalence of <i>BRCA1</i> and <i>BRCA2</i> small mutation and large genomic rearrangements in breast cancer patients visiting a genetic counseling clinic
Authors: Ji Yeon Sohn, Boyoung Park, Kyong-Ah Yoon, Soo Jin Park, Moo Hyun Lee, Eun Hae Cho, Keun Seok Lee, Myong Cheol Lim, Sun-Young Kong, Eun Sook Lee
Journal: Cancer Research (2016)

Abstract BACKGROUND: This study was conducted to investigate mutation prevalence of the BRCA1 and BRCA2 genes in breast cancer patients, including both small mutations and large genomic rearrangements (LGRs) following the patients in the process of genetic counseling. METHODS: A total of 358 breast cancer patients who visited genetic counseling clinic and screened for BRCA1/2 mutation at the National Cancer Center were included. Among the non-carriers by direct sequencing, a subset of patients who were agreed on participation of the research were screened for the presence of LGRs using a multiple ligation-dependent probe amplification (MLPA) assay. Clinico-pathologic characteristics of cancer were evaluated thorough medical record review and characteristics for those who found BRCA mutation through MLPA were described. RESULTS: 53 (14.8%) mutation carriers were identified. The frequency of BRCA small mutations in specific subgroups was as follows: 18.0% of patients with a family history, 12.8% of early-onset breast cancer, and 20.6% of bilateral breast cancer patients. MLPA identified BRCA1 LGRs in 3 (1.5%) out of 204 patients with BRCA1 and BRCA2 small mutation-negative results. Those with LGRs showed higher probabilities of BRCA mutation carriers estimated by risk assessment models and receptor negatives of tumor immunohistochemistry. CONCLUSIONS: The prevalence of BRCA1/2 mutation prevalence in breast cancer patients with family history or personal risk factors were comparable to previous Korean studies. MLPA to screen for mutations in the BRCA1 gene could be recommended for breast cancer patients negative for small mutations. To specify proper targets of MLPA, probabilities of carrying BRCA1/2 mutation and tumor receptor status could be considered. Citation Format: Ji Yeon Sohn, Boyoung Park, Kyong-Ah Yoon, Soo Jin Park, Moo Hyun Lee, Eun Hae Cho, Keun Seok Lee, Myong Cheol Lim, Sun-Young Kong, Eun Sook Lee. Prevalence of BRCA1 and BRCA2 small mutation and large genomic rearrangements in breast cancer patients visiting a genetic counseling clinic. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3474.
Second Bacteremia During Antibiotic Treatment In Children With Acute Myeloid Leukemia: A Report From The Canadian Infections In AML Research Group
Authors: Thai Hoa Tran, Rochelle Yanofsky, Donna Johnston, David Dix, Biljana Gillmeister, Marie-Chantal Ethier, Carol Portwine, Victoria E. Price, David Mitchell, Sonia Cellot, Victor A. Lewis, Shayna Zelcer, Mariana Silva, Bruno Michon, Lynette Bowes, Kent Stobart, Josee Brossard, Joseph Beyene, Lillian Sung
Journal: Blood (2013)
Abstract 2153: ATP7B is a promising therapeutic target for uterine leiomyosarcoma
Authors: Mamoru Kakuda
Journal: Cancer Research (2016)

Abstract Objective Resistance to platinum drugs remains a significant problem in uterine leiomyosarcoma (LMS). We investigated the role of ATP7B in the resistance to platinum drugs in LMS using both in vitro and in vivo models. Methods The expression of the typical platinum transporters (MDR1, MRP2, ATP7A, and ATP7B) was examined in LMS cell lines using Western blotting analysis. ATP7A expression was investigated by immunohistochemistry (IHC) using clinical samples of LMS. IC50 values to cisplatin were measured in SK-LMS cells, SK-LMS-ATP7B-suppressed cell line (SK-LMS-7B cells), which permanently transfected PRS ATP7B shRNA vector. We established xenografted mice by inoculating SK-LMS cells and SK-LMS-7B cells, and examined in vivo platinum sensitivity with cisplatin for both tumors. This study was approved by the Institutional Review Board and the Ethics Committee of the Osaka University Hospital (approval #10302, approved on March 11, 2011). Results The expression of ATP7B was identified in the SK-LMS cells. ATP7B expression was identified in 70% (14/20) of the LMS clinical samples using IHC. The IC50-values to cisplatin improved from 17 mM to 4.3 mM after the suppression of ATP7B in SK-LMS-7B cells. A significant anti-tumor effect of cisplatin was observed in SK-LMS-7B xenografted mice than in SK-LMS xenografted mice. We also identified CuSO4 as an preferentially inhibitor of ATP7B in vitro. Conclusion ATP7B is associated with platinum resistance. CuSO4 acting as an inhibitor of ATP7B can be a therapeutic target for LMS. Citation Format: Mamoru Kakuda. ATP7B is a promising therapeutic target for uterine leiomyosarcoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2153.
Abstract 966: Circulating exosomal miRNAs as potential biomarker in liposarcoma
Authors: Lucia Casadei, Chad Creighton, Kara Batte, Dina Chelouche-Lev, Carlo M. Croce, Raphael E. Pollock
Journal: Cancer Research (2016)

Abstract Liposarcoma (LPS) is the most common soft tissue sarcoma histological subtype. Despite the development of combined modality treatments in recent years, a significant proportion of patients respond poorly to chemotherapy, leading to local recurrence or distant metastasis. Thus, early detection of recurrent or metastatic disease or early decision making could improve patient prognosis. However, there are no useful biomarkers for these purposes. Thus, the discovery of novel biomarkers to detect tumors, predict their drug sensitivity, and monitor their progression is one of the most important challenges that must be overcome. miRNAs are short (approximately 22 nucleotides in length) non-coding RNAs (ncRNAs) that regulate gene expression by binding to specific mRNA targets and promoting their degradation and/or translational inhibition; since their discovery in body fluids (secreted in cell-borne membrane vesicles or associated with macromolecular complexes), circulating blood-borne microRNAs are being investigated as potent minimally invasive biomarkers of several diseases including tumors. In this study, our goal is to identify potential biomarkers in the peripheral blood of LPS patients that could be useful for LPS diagnostic, prognostic and therapeutic purposes. To determine the miRNA expression profiles of LPS in peripheral blood (PB) and in peripheral blood exosomes (PBX), a series of 16 human LPS patient specimens and 8 healthy controls was analyzed on a miRNA microarray platform capable of detecting 800 human miRNAs (nCounter Human microRNA expression Assay Nanostring v3). Validation of the array was performed by qRT-PCR on a new set of samples (10 human LPS and 9 healthy controls). To identify differentially expressed miRNAs, we compared miRNAs expression profiles from PBX of 15 patients to 8 healthy samples. A total of 26 miRNAs were significantly upregulated and 3 miRNAs were significantly down regulated (p&amp;lt;0.004). When we compared miRNA expression profiles from PB to healthy controls, fewer miRNAs were consistently deregulated (18 miRNAs were upregulated and 3 miRNAs were downregulated, p&amp;lt;0.02). Moreover the miRNAs found to be consistently deregulated in PB were all also significantly deregulated in the PBX. Validation of the miRNA panel in an independent cohort of LPS patients confirmed this signature. Our study has identified a specific miRNA signature in circulating exosomes that may have a novel role in the diagnosis, prognosis and or treatment of LPS patients in a clinical setting. Citation Format: Lucia Casadei, Chad Creighton, Kara Batte, Dina Chelouche-Lev, Carlo M. Croce, Raphael E. Pollock. Circulating exosomal miRNAs as potential biomarker in liposarcoma. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 966.
Abstract 1828: Analysis of putative serum biomarker candidates for cardiotoxicity prediction in a cohort of early stage breast cancer patients treated with docetaxel, cyclophosphamide, and bevacizumab
Authors: David W. Murray, Alice C. O’Farrell, Giuseppe Gullo, Ashwini Maratha, Patrick Dicker, Mairin Rafferty, Verena Murphy, Bonnie Ky, William M. Gallagher, Norma O’Donovan, John Crown, Annette T. Byrne
Journal: Cancer Research (2016)

Abstract Background: Breast cancer is the leading cause of cancer in women, with 1.8 million patients diagnosed globally each year. In early stage disease, anthracycline regimens are commonly employed, but the risk of cardiotoxicity is high. Replacing anthracyclines with taxanes in combination with cyclophosphamide may improve response [1] and Bevacizumab (BVZ) may provide addtional benefit. However, as BVZ can cause hypertension and increased risk of cardiac failure, a rationale exists for studying biomarkers of cardiotoxicity in this setting. Methods: We assessed a panel of biomarkers in n = 57 early stage breast cancer patients whom underwent docetaxel/cyclophosphamide/BVZ therapy on the TC-Avastin Trial (NCT00911716). Serum was collected prior to treatment and at 3 months. Cardiotoxicity was defined as decline in left ventricular ejection fraction ≥ 10% to &amp;lt;55% over 1 year treatment + 2 year follow-up. Cardiac troponin I and T [cTnI, cTnT], Endothelin-1, Galectin-3, Placental Growth Factor [PlGF], Platelet Derived Growth Factor, Vascular Endothelial Growth Factor receptors 1 and 2, total nitrous oxide NO and myeloperoxidase [MPO]) were screened by ELISA in a subgroup (n = 16). Pilot and recently published findings [2] implicated PlGF, cTn1 and MPO, which were subsequently assessed in the larger cohort. Results: Changes in serum MPO or cTnI were not related to cardiotoxicity when analysed in the larger cohort. However, a “cut-off” PlGF fold change of 0.99 could differentiate patients who developed cardiotoxicity from those that did not. 74% of cardiotoxicity patients, compared to only 35% of non-cardiotoxicity fell below the 0.99 cut-off. Conversely, 65% of non-cardiotoxicity patients, compared to 25% of cardiotoxicity patients fell above the cut-off (p = 0.0042). Conclusions: Our data suggest that decreased PlGF at 3 months may predict cardiotoxicity. These observations require further validation. This work was funded by AngioTox, an EC FP7 IAPP Marie Curie Award (Grant Agreement 251528). [1]Jones et al., J. Clin. Oncol.27, 1177-1183 (2009); [2] Putt et al., Clin. Chem 61, 1164-1172 (2015). Citation Format: David W. Murray, Alice C. O’Farrell, Giuseppe Gullo, Ashwini Maratha, Patrick Dicker, Mairin Rafferty, Verena Murphy, Bonnie Ky, William M. Gallagher, Norma O’Donovan, John Crown, Annette T. Byrne. Analysis of putative serum biomarker candidates for cardiotoxicity prediction in a cohort of early stage breast cancer patients treated with docetaxel, cyclophosphamide, and bevacizumab. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1828.