tbuckley/cabot-search huggingface dataset:
Inhibition of the receptor tyrosine kinase ROR1 by anti-ROR1 monoclonal antibodies and siRNA induced apoptosis of melanoma cells.
Authors: Mohammad Hojat Farsangi, Fatemeh Ghaemimanesh, Amir Hossein Daneshmanesh, Ali-Ahmad Bayat, Jafar Mahmoudian, Mahmood Jeddi-Tehrani, Hakan Mellstedt
Journal: Journal of Clinical Oncology (2013)

e22198 Background: The receptor tyrosine kinase ROR1 has important functions during normal embryogenesis. It is overexpressed and of importance for the survival of different malignancies, including lung adenocarcinoma, breast cancer and chronic lymphocytic leukemia (CLL). ROR1 inhibition in CLL cells and cell lines with high expression of ROR1 induced specific apoptosis of the cells. There is however little information on the expression and function of ROR1 in melanoma. Here, we investigated ROR1 expression, phosphorylation and the effects of anti-ROR1 monoclonal antibodies (mAbs) and ROR1 suppressing siRNA on seven melanoma cell lines. Methods: ROR1 expression and phosphorylation was analysed in a series of malignant melanoma cell lines using RT-PCR, immunocytochemistry, flow cytometry and western blot. Annexin V/PI staining, MTT assay, PARP and caspase 8 and 9 cleavage as well as MCL-1 protein were used for detection of apoptosis induced by anti-ROR1 mAbs. The cytotoxic effects of anti-ROR1 mAbs were evaluated in the absence or presence of complement (CDC) or immune effector cells (ADCC). Transfection of melanoma cell lines using ROR1 siRNA was used for gene silencing. Results: ROR1 was shown to be overexpressed to a varying degree at protein level. ROR1 was phosphorylated at tyrosine and serine residues. Three out of four anti-ROR1 mAbs (clones 3H9, 5F1 and 1A8) induced a significant direct apoptosis of the ESTDAB049, ESTDAB112, DFW and A375 cell lines as well as cell death in the presence of complement or immune effector cells. ESTDAB081 and 094 cell lines were resistant to direct apoptosis of the four anti-ROR1 mAbs alone compared to the other melanoma cell lines, but not to complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC). ROR1 siRNA transfection induced down-regulation of the ROR1 expression both at the mRNA and protein levels proceeded by a significant apoptosis of the melanoma cells. Conclusions: The results indicate that ROR1 may play an important role in the survival of melanoma cells. The surface expression of ROR1 on melanoma cells may support the notion that ROR1 might be a suitable targeted for mAb therapy.
Health‐related quality of life in patients with melanoma – characterization of a Swedish cohort
Authors: H. Tufvesson Stiller, R. Mikiver, S. Uppugunduri, C. Lindholm, E. Månsson Brahme, M. Schmitt‐Egenolf
Journal: British Journal of Dermatology (2019)

Only few studies that have investigated the Health-Related Quality of Life (HR-QoL) in melanoma patients 1-4 , reviewed in Chernyshov et al.5 . This is to the best of our knowledge the first popula ...
P14.120 Phase II study of weekly carboplatin in pretreated adult malignant gliomas
Authors: V Villani, A Pace, A Vidiri, A Tanzilli, F Sperati, I Terrenato, M Carosi, B Casini, M Maschio, T koudriavtseva, F Cognetti, A Fabi
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Patients with relapse of recurrent glioma have a poor outcome and limited treatment options. The aim of this study is to investigate the clinical benefit and tolerability of weekly intravenous administration of carboplatin-based monotherapy in adult glioma patients who had progressed from previous chemotherapy lines based on temozolomide and nitrosoureas MATERIAL AND METHODS This was a single arm, Phase II study. Eligibility criteria included progressive or recurrent malignant glioma after radiotherapy and chemotherapy-based treatments and Karnofsky Performance Status (KPS) &gt; 60. RESULTS Thirty-two patients (median age: 43.5 y) were enrolled to receive weekly carboplatin monotherapy in intravenous mode of administration. The median duration of response was 7.3 months with an overall disease control rate of 31.3%. Median progression-free survival (PFS) was 2.3 months while overall survival (OS) was 5.5 months. Patients achieving clinical benefit exhibited a longer PFS (4.6 vs 1.5 months; p&gt;0.001) and OS (7.9 vs 3.2 months; p=0.041) compared to those not achieving clinical benefit. CONCLUSION Our findings show that single agent, weekly, intravenous carboplatin may have a role in the treatment patients with recurrent malignant glioma
Postnatal checks for new mothers need to be properly funded, charity tells government
Authors: Jacqui Wise
Journal: BMJ (2019)

Almost half (47%) of new mothers get less than three minutes or no time to discuss their mental and physical health at the routine six week postnatal check-up, according to a survey by the National Childbirth Trust (NCT).

The charity is calling on the government to provide funding for a full postnatal check-up so that GPs have sufficient time to talk to a new mother about her health and wellbeing rather than …
Assessment for Perioperative Hyperglycemia Prior to Total Joint Replacement in Patients With and Without Diabetes
Authors: Lindsey A. MacFarlane, Yinzhu Jin, Patricia D. Franklin, Joyce Lii, Jeffrey N. Katz, Seoyoung C. Kim
Journal: JAMA Network Open (2019)

Part A or B 136 093 Medicare Part D 8171 Excluded owing to ICD-9 code for complication related to diabetes but no ICD-9 code for diabetes 46 66 236 Excluded 66 094 Age <65 y 26 No claims in 260 days 70 Both hip and knee replacement on index date Bilateral procedureThe criteria for exclusions were checked consecutively. ICD-9 indicates International Classification of
Effect of LIM domain only (LMO2) protein expression on survival in multiple myeloma patients.
Authors: Engin Kelkitli, Memis Hilmi Atay, Levent Yildiz, Mehmet Turgut
Journal: Journal of Clinical Oncology (2013)

e19500 Background: Better understanding of the biology of myeloma paved the way for new treatments that target myeloma cells which are playing a critical role in the pathogenesis of the disease and microenvironments of the bone marrow. LMO2 (LIM domain only 2) is located on 11p13 and belongs to a family of 4 genes encoding LIM only proteins, that are transcription regulators that control cell fate in normal hematopoiesis. LMO2 has been identified as a novel oncogene associated with carcinogenesis and better prognosis in several malignant tumors such as pancreatic, prostate cancer. We examined if LMO2 protein expression can predict the outcome in MM patients. Methods: Forty-one patients were enrolled with MM admitted to our hospital. Immunohistochemistry on bone marrow biopsy material for LMO2 protein was performed in our hospital pathology laboratory, and staining in greater than 30% of plasma cells was assigned positive score. Results: Of the 41 patients , 21 were male and 20 were female. The mean age was 62±11. The demographic characteristics of patients are shown in the table. Thirty patients had LMO2 protein expression in bone marrow samples whereas in eleven patients LMO2 protein expression was not detected. LMO2 negativity were more frequent in patients with type of lambdaM protein (P=0.04). The risk of death was increased in the patients with LMO2 protein expression compared with patients who had no LMO2 protein expression. While overall survival was %100 in the patients with no LMO2 protein expression, it was %76.7 in the patients with LMO2 protein expression (according to Kaplan Meier test, long rank p=0.04). Conclusions: We report that the no LMO2 protein expression is correlated with improved overall survival in the MM patients. This method is simple, inexpensive, and effective. We suggest that the expression of LMO2 should be tested in a larger series of MM patients. [Table: see text]
Measles, Mumps, Rubella Vaccination and Autism
Authors: Anders Hviid, Jørgen Vinsløv Hansen, Morten Frisch, Mads Melbye
Journal: Annals of Internal Medicine (2019)

Letters3 September 2019Measles, Mumps, Rubella Vaccination and AutismAnders Hviid, DrMedSci, Jørgen Vinsløv Hansen, PhD, Morten Frisch, DrMedSci, and Mads Melbye, DrMedSciAnders Hviid, DrMedSciStatens Serum Institut, Copenhagen, Denmark (A.H., J.V.H., M.F., M.M.), Jørgen Vinsløv Hansen, PhDStatens Serum Institut, Copenhagen, Denmark (A.H., J.V.H., M.F., M.M.), Morten Frisch, DrMedSciStatens Serum Institut, Copenhagen, Denmark (A.H., J.V.H., M.F., M.M.), and Mads Melbye, DrMedSciStatens Serum Institut, Copenhagen, Denmark (A.H., J.V.H., M.F., M.M.)Author, Article, and Disclosure Informationhttps://doi.org/10.7326/L19-0383 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:Dr. Mawson suggests that we should have compared the risk for autism between fully vaccinated and completely unvaccinated groups of children or between children who only received the MMR vaccine and their completely unvaccinated counterparts. Figure 3 of our article does compare the risk for autism in MMR-vaccinated and MMR-unvaccinated children among the subset of children who did not receive the DTaP-IPV/Hib vaccine in infancy, resulting in a hazard ratio of autism of 1.09 (95% CI, 0.77 to 1.56). Comparing children who received both 2 or more DTaP-IPV/Hib vaccines in infancy and the MMR vaccine with children who ... Author, Article, and Disclosure InformationAffiliations: Statens Serum Institut, Copenhagen, Denmark (A.H., J.V.H., M.F., M.M.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M18-2101. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoMeasles, Mumps, Rubella Vaccination and Autism Anders Hviid , Jørgen Vinsløv Hansen , Morten Frisch , and Mads Melbye Measles, Mumps, Rubella Vaccination and Autism Jake Crosby Measles, Mumps, Rubella Vaccination and Autism Anthony R. Mawson Metrics Cited byComprehensive investigations revealed consistent pathophysiological alterations after vaccination with COVID-19 vaccinesReversible regression in early childhoodThe VACCINES Act: Deciphering Vaccine Hesitancy in the Time of COVID-19Culturally diverse families of young children with ASD in Sweden: Parental explanatory modelsSeroprevalence of Measles, Mumps, and Rubella antibodies among Southwestern Libyan students.Vaccination 3 September 2019Volume 171, Issue 5Page: 388KeywordsAutismChildrenDisclosureHazard ratioMMR vaccineStatistical methodsSurvival analysisVaccines ePublished: 3 September 2019 Issue Published: 3 September 2019 Copyright & PermissionsCopyright © 2019 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Radium-223 chloride (Ra-223) impact on skeletal-related events (SREs) and ECOG performance status (PS) in patients with castration-resistant prostate cancer (CRPC) with bone metastases: Interim results of a phase III trial (ALSYMPCA).
Authors: A. Oliver Sartor, Daniel Heinrich, Joe M. O'Sullivan, Sophie D. Fossa, Ales Chodacki, Pawel J. Wiechno, John P. Logue, Mihalj Seke, Anders Widmark, Dag Clement Johannessen, Sten Nilsson, Peter Hoskin, David Bottomley, Robert Edward Coleman, Nicholas J. Vogelzang, C. Gillies O'Bryan-Tear, Jose E. Garcia-Vargas, Minghua Shan, Chris Parker
Journal: Journal of Clinical Oncology (2012)

4551 Background: Ra-223, a 1st-in-class alpha-pharmaceutical, targets bone metastases (mets) with high-energy alpha-particles of short range (&lt;100 μm). ALSYMPCA, a phase III, double-blind, randomized, multinational study, compared Ra-223 plus best standard of care (BSC) v placebo (pbo) plus BSC in patients (pts) with bone mets in CRPC. The primary endpoint was OS; secondary endpoints included SREs and ECOG PS. Methods: Eligible pts had progressive, symptomatic CRPC with ≥ 2 bone mets on scintigraphy and no known visceral mets; were receiving BSC; and either previously received docetaxel, were docetaxel ineligible, or refused docetaxel. Pts were randomized 2:1 to 6 injections of Ra‑223 (50 kBq/kg IV) q4 wks or matching pbo and stratified by prior docetaxel use, baseline ALP level, and current bisphosphonate use. Results: 921 pts were randomized from 6/2008-2/2011. In a planned interim analysis (n = 809), Ra-223 significantly improved OS v pbo (median OS 14.0 v 11.2 mo, respectively; two-sided P = .00185; HR = .695; 95% CI, .552-.875).SREs were lower in the Ra-223 v pbo group, and time to 1st SRE was significantly delayed (median time to SRE 13.6 mo v 8.4 mo, respectively; P = .00046; HR = .610; 95% CI, .461-.807). The proportion of pts with ECOG PS deterioration (≥ 2 points) was less in Ra-223 v pbo group at Wk 12 and Wk 24 (4%, 15/389 v 9%, 16/180 and 7%, 16/236 v 12%, 10/83, respectively). Time to ECOG PS deterioration (≥ 2 points) was significantly delayed by Ra-223 v pbo (P = .003; HR = .62; 95% CI, .46-.85). Conclusions: Ra-233 significantly delayed time to 1st SRE and SRE components, notably SCC. Fewer pts in the Ra-223 group had ECOG PS deterioration. Ra-223 improves OS with excellent safety and may provide a new standard of care for CRPC pts with bone mets. [Table: see text]
Phase II Study of the ALK5 Inhibitor Galunisertib in Very Low-, Low-, and Intermediate-Risk Myelodysplastic Syndromes
Authors: Valeria Santini, David Valcárcel, Uwe Platzbecker, Rami S. Komrokji, Ann L. Cleverly, Michael M. Lahn, Jan Janssen, Yumin Zhao, Alan Chiang, Aristoteles Giagounidis, Susan C. Guba, Ivelina Gueorguieva, Allicia C. Girvan, Mariana da Silva Ferreira, Tushar D. Bhagat, Kith Pradhan, Ulrich Steidl, Ashwin Sridharan, Britta Will, Amit Verma
Journal: Clinical Cancer Research (2019)

Abstract Purpose: Overactivation of TGF-β signaling is observed in myelodysplastic syndromes (MDS) and is associated with dysplastic hematopoietic differentiation. Galunisertib, a first-in-class oral inhibitor of the TGF-β receptor type 1 kinase (ALK5) has shown effectiveness in preclinical models of MDS and acceptable toxicity in phase I studies of solid malignancies. Patients and Methods: A phase II multicenter study of galunisertib was conducted in patients with very low-, low-, or intermediate-risk MDS by the Revised International Prognostic Scoring System criteria with hemoglobin ≤ 10.0 g/dL. Patients received oral galunisertib 150 mg twice daily for 14 days on/14 days off. Results: Ten of 41 evaluable patients (24.4%; 95% confidence interval, 12.4–40.3) achieved hematologic improvement erythroid response by International Working Group (IWG) 2006 criteria. A total of 18 of 41 patients (43.9%) achieved erythroid response as per IWG 2000 criteria. Nine of 28 (32.1%) of transfusion-dependent patients had hematologic improvement. A total of 18 of 41 (44%) patients had a significant reduction in fatigue. Overall median duration of response was 90 days in all patients. Rigorous stem and progenitor flow cytometry showed that patients with an early stem cell differentiation block were more likely to respond to galunisertib. The most common treatment-emergent adverse events were grade 1 or 2 in 20 (49%) of 41 patients, including any-grade fatigue (8/41, 20%), diarrhea (7/41, 17%), pyrexia (5/41, 12%), and vomiting (5/41, 12%). Conclusions: In summary, galunisertib treatment has an acceptable safety profile and was associated with hematologic improvements in lower- and intermediate-risk MDS, with responses in heavily transfusion-dependent patients and in those with signs of an early stem cell differentiation block.
Population-Level Symptom Assessment Following Pancreaticoduodenectomy for Adenocarcinoma
Authors: Stephanie Tung, Laura E. Davis, Julie Hallet, Michail N. Mavros, Alyson L. Mahar, Lev D. Bubis, Ahmed Hammad, Haoyu Zhao, Craig C. Earle, Lisa Barbera, Natalie G. Coburn, Mina Siqqidui, Qing Li, Maryam Elmi, Elizabeth Shin, Eugene Hsieh, Nik Goyert
Journal: JAMA Surgery (2019)

Postoperative morbidity associated with pancreaticoduodenectomy (PD) for pancreatic adenocarcinoma (PA) remains as high as 70%. However, to our knowledge, few studies have examined quality of life in this patient population.To identify symptom burden and trajectories and factors associated with high symptom burden following PD for PA.This population-based cohort study of patients undergoing PD for PA diagnosed between 2009 and 2015 linked population-level administrative health care data to routinely prospectively collected Edmonton Symptom Assessment System (ESAS) scores from 2009 to 2015, with a data analysis undertaken in 2018.Baseline characteristics, including age, sex, income quintile, rurality, immigration status, and comorbidity burden, as well as treatment characteristics, including year of surgery and receipt of chemotherapy.The outcome of interest was moderate to severe symptoms (defined as ESAS ≥4) for anxiety, depression, drowsiness, lack of appetite, nausea, pain, shortness of breath, tiredness, and impaired well-being. The monthly prevalence of moderate to severe symptoms was presented graphically for each symptom. Multivariable regression models identified factors associated with the reporting of moderate to severe symptoms.We analyzed 6058 individual symptom assessments among 615 patients with PA who underwent resection (285 women [46.3%]) with ESAS data. Tiredness (443 [72%]), impaired well-being (418 [68%]), and lack of appetite (400 [65%]) were most commonly reported as moderate to severe. The proportion of patients with moderate to severe symptoms was highest immediately after surgery (range, 14%-66% per symptom) and decreased over time, stabilizing around 3 months (range, 8%-42% per symptom). Female sex, higher comorbidity, and lower income were associated with a higher risk of reporting moderate to severe symptoms. Receipt of adjuvant chemotherapy was not associated with the risk of moderate to severe symptoms.There is a high prevalence of symptoms following PD for PA, with improvement over the first 3 months following surgery. In what to our knowledge is the largest cohort reporting on symptom burden for this population, we have identified factors associated with symptom severity. These findings will aid in managing patients' perioperative expectations and designing strategies to improve targeted symptom management.
Epidemiology of BCC and cSCC in the U.K. 2013‐15
Authors: Z.C. Venables, T. Nijsten, K.F. Wong, P. Autier, J. Broggio, A. Deas, C.A. Harwood, L.M. Hollestein, S.M. Langan, E. Morgan, C. Proby, J. Rashbass, I.M. Leigh
Journal: British Journal of Dermatology (2019)

The two most common types of skin cancer (tumour) are called basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC). BCC and cSCC have previously been removed from U.K. national cancer statistics, collected by cancer registries, because it was difficult to accurately estimate tumour counts. Improvements to registry data collection of BCC and cSCC since 2013 have resulted in the largest and most complete dataset of BCC and cSCC in the world. Therefore, the aim of this study was to provide better estimates of BCC and cSCC tumour counts using registry data in the U.K. This study confirms that skin cancers are four times more common than any other cancer in the U.K. The authors were able to show that BCCs and cSCCs affected over 210,000 people in the U.K in 2015 with BCCs affecting 3 in 1000 people and cSCCs affecting 1 in 1000 people in 2015 alone. As they most commonly affect elderly people, it is not surprising that incidence rates are increasing by around 5% per year. Although they are less dangerous than melanomas and therefore there is less public awareness of BCC and cSCC, together, they are more than ten times more common than melanomas. This study exposes the previously unreported burden of skin cancers in the U.K. and highlights the importance of skin cancer prevention through protection against excessive ultraviolet radiation through natural (sunshine) or unnatural (tanning booths) exposure.
Non-IgM Secreting Lymphoplasmacytic Lymphoma - Experience of a Reference Center for Waldenstrom Macroglobulinemia
Authors: Gilad Itchaki, Toni Dubeau, Andrew Keezer, Kirsten Meid, Lian Xu, Guang Yang, Zachary R Hunter, Steven P Treon, Jorge J. Castillo
Journal: Blood (2018)
P14.09 INITIAL GLOBAL SYMPTOMS IN GLIOBLASTOMA ARE OFTEN MISINTERPRETED AND ASSOCIATED WITH SHORTER SURVIVAL
Authors: H Bruhn, C Dahle, M Vrethem, R Henriksson, J Lindh
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND A seizure as the only symptom before diagnosing glioblastoma improves survival rate. Apart from seizures, the main presenting symptom of glioma in adults is cognitive dysfunction. The effect of generalized symptoms or loss of function on lead times and survival of glioblastoma has not been studied. Generalized symptoms include cognitive dysfunction, headache, dizziness and fatigue. Loss of function comprise paresis, sensory deficit and speech aberrations. The objective of this study was to evaluate the influence of different presenting symptoms regarding health care level, lead times and survival. MATERIAL AND METHOD Medical case notes regarding 189 consecutive patients with histopathologically verified glioblastoma, were reviewed for information about the date and level of care of the first medical appointment, presenting symptom/s, and date of the diagnostic radiology. The extent of surgery was noted. Data on oncologic treatment was retrieved. Summary statistics were provided for patient demographics and treatment factors. The estimates of overall survival were calculated using the Kaplan-Meier method. Survival time was calculated from the date of radiological diagnosis. RESULTS The majority of patients (66%) presented with generalized symptoms, which significantly reduced survival compared to not having generalized symptoms (mean survival 10.5 months vs 19.9 months, p=0.001). The most common generalized symptom was cognitive dysfunction which further reduced survival (mean survival 9.0 months, p=0.0001). Among the different cognitive aberrations, personality change and memory impairment were associated with a significantly poorer survival, (mean survival 7.9 months, p=0.015 and 8.0 months p=0.010, respectively). Disorientation also significantly reduced survival (mean survival 8.2 months p=0.001). Presenting with loss of function (58%) did not influence survival (mean survival 12.3 months). 32% of patients with an epileptic seizure as initial symptom had significantly prolonged survival compared to those not having an epileptic seizure (mean 18.9 months vs 11.0 months p=0.002). When comparing focal and secondary generalized epileptic seizures, focal epileptic seizures were more favorable. The first medical appointment was evenly distributed between primary health care and the emergency units. 8.4% of patients had multiple contacts in primary health care without being admitted to radiology or specialized care. All but one of them presented with generalized symptoms. CONCLUSION Glioblastoma patients presenting with generalized symptoms such as cognitive dysfunction are difficult to identify and have significantly poorer survival than other glioblastoma patients. Patients presenting with an epileptic seizure have shorter leadtime and longer survival.