tbuckley/cabot-search huggingface dataset:
GERM-11. TREATMENT AND OUTCOMES OF CENTRAL NERVOUS SYSTEM NON-GERMINOMATOUS GERM CELL TUMORS WITH EARLY RELAPSE DURING INDUCTION CHEMOTHERAPY
Authors: Hung Tran, Ashley Margol, Nathan Robison, Kenneth Wong, Jonathan Finlay, Girish Dhall
Journal: Neuro-Oncology (2018)

Prognosis for central nervous system (CNS) non-germinomatous germ cell tumor (NGGCT) patients that relapse during induction is poor. We present our experience for these patients. Medical records of CNS NGGCT patients at Children’s Hospital Los Angeles between 2008 and 2014 were reviewed for clinical characteristics, treatment, and outcome. Eight (27.6%) of 29 patients relapsed or were refractory during induction chemotherapy, an average of 6.3 months from diagnosis. Five patients had pineal primaries and three patients had synchronous pineal and suprasellar tumors. All patients had tumor marker (TM) elevation in serum and/or CSF; four patients underwent biopsy. Three patients had local relapse, two local and ventricular, and three had TM-only relapse. All received re-induction chemotherapy with gemcitabine 800mg/m2, paclitaxel 170mg/m2, and oxaliplatin 100mg/m2 (GemPOx). After re-induction, the three TM-only relapses continued to have no evidence of disease (NED) radiographically, three patients showed a partial response (PR), and two patients had stable disease (SD). Seven patients received high-dose chemotherapy with a thiotepa-based regimen followed by autologous stem cell rescue (ASCR). After ASCR, radiographically, three TM positive cases continued to be NED, three had a PR, and one patient had SD. Six received additional irradiation post-transplant, of which five are alive. Six of eight relapsed/refractory patients are alive at 41, 42, 66, 71, 78, 79 months from initial diagnosis. Relapsed/refractory CNS NGGCT patients can be successfully salvaged by re-induction chemotherapy followed by consolidation with a thiotepa-based myeloablative regimen and re- irradiation.
The Urgent Need in Oncology for a Comprehensive Cost of Care Task Force
Authors: Joshua D. Palmer, Tejash T. Patel, Scot A. Fisher
Journal: JAMA Oncology (2018)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Oncology HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Oncology journal
New Relief for Opioid Withdrawal
Authors: Rebecca Voelker
Journal: JAMA (2018)

Lofexidine hydrochloride has received FDA approval to help alleviate opioid withdrawal symptoms. It’s the first nonopioid medication approved to relieve the misery of symptoms such as nausea, vomiting, profuse sweating, and tachycardia. In March an FDA advisory committee recommended the approval.
EPEN-19. SUPRATENTORIAL EPENDYMOMAS - L1CAM EXPRESSION AND RELA FUSION, THEIR CORRELATION WITH CLINICOPATHOLOGICAL FEATURES
Authors: Gouri Anvekar, Mamta Gurav, Omshree Shetty, Vinayak Kadam, Ayushi Sahay, Girish Chinnaswamy, Prakash Shetty, Aliasgar Moiyadi, Tejpal Gupta, Rakesh Jalali, Sridhar Epari
Journal: Neuro-Oncology (2018)

This study was undertaken to evaluate the frequency of RELA fusion 1/2 in supratentorial ependymomas and its L1CAM and cylin D1 expression. MATERIALS AND Evaluated for histological features, immunohistochemical parameters (p53 protein, cyclin D1 and L1CAM expression) and rt-PCR for RELA fusion 1/2. The clinical parameters of these cases were also noted. Total 71 cases; age range: 1-76yrs (interquartile range: 6-24yrs). Male (n=46): female (n=25) ratio 1.8: 1. Intraparenchymal-58 (commonly parietal), ventricular-13. Histological subtypes were subependymoma (grade I, n=4), ependymoma (grade II, n=8), anaplastic ependymoma (grade III, n=54) and ependymoma with atypical features (intermediate between grade II and III, n=5). 64.7% (44/68) showed p53 protein over-expression, 79.7% (55/69) cyclin D1 over-expression and 57.7% (41/71) L1CAM positivity. RELA fusion 1/2 positivity was detected in 45% of the cases (27/60; 22 Type 1, 5 Type 2). 63.2% (24/38) were ≤14 years (0-3yrs: 5/8, 4-9yrs: 12/17, 10-14yrs: 7/13). All RELA fusion-positive cases showed p53 protein, cyclin D1 and L1CAM over-expression while none of the cyclin D1 or L1CAM negative cases showed RELA fusion. With RELA fusion by rt-PCR as the reference test, L1CAM IHC showed 100% sensitivity, 59.4% specificity, 66.7% PPV and 100% NPV. RELA fusions 1/2 are common in younger age (≤ 14yrs) and identified across all histological subtypes except subependymoma. All L1CAM and cyclin D1 negative cases were also negative for RELA fusion, thus combined L1CAM and cyclin D1 negativity can be used as predictive maker for RELA fusion negativity.
ATRT-34. TARGETING PRIMARY CILIOGENESIS IN ATYPICAL TERATOID/RHABDOID TUMORS
Authors: Lena Blümel, Kornelius Kerl, Nan Qin, Johannes Berlandi, Katharina Thiel, Isabel Tegeder, Astrid Jeibmann, Daniel Picard, Maike Langini, Kai Stühler, Frauke-Dorothee Meyer, Bastian Malzkorn, Max C Liebau, Pascal D Johann, Serap Erkek, Marcel Kool, Stefan M Pfister, Michael C Frühwald, Arndt Borkhardt, Guido Reifenberger, Martin Hasselblatt, Marc Remke
Journal: Neuro-Oncology (2018)

Atypical teratoid/rhabdoid tumors (AT/RT) are among the most common malignant brain tumors in infants. Comprehensive genomic studies revealed three distinct molecular subgroups (AT/RT-TYR, -MYC and -SHH). As primary cilia (PC) have already been shown to play a central role in other tumor entities, we aimed to characterize the distribution of PC across AT/RT subgroups and to target primary ciliogenesis in these tumors with dismal prognosis. We performed immunofluorescence to detect PC in AT/RT cell lines (n=2) and primary tumor sections (n=13). The functional role of PC was investigated by knockdown of KIF3A and pharmacological inhibition with Ciliobrevin D in vitro. The relevance of primary ciliogenesis in AT/RT biology was further elucidated using a fly model of SMARCB1 deficiency. We detected PC in both AT/RT cell lines and all primary tumors investigated in this study. Notably, we observed a significant subgroup-specific difference in the proportion of PC-positive cells. Specifically, AT/RT-TYR demonstrated the highest percentage of ciliated cells. Knockdown of KIF3A significantly reduced cell proliferation and stem cell properties. Additionally, death receptor 5 signaling was significantly up-regulated. Pharmacological inhibition by Ciliobrevin D phenocopied these results, specifically after induction of primary ciliogenesis through serum starvation. In a fly model of SMARCB1 deficiency, concomitant knockdown of several cilia-associated genes resulted in a substantial shift of the lethal phenotype with >20% of flies reaching adulthood. In conclusion, these results implicate PC as a key feature of AT/RT biology and suggest primary ciliogenesis as a potential therapeutic target, especially in AT/RT-TYR.
MBRS-45. EXPRESSION AND FUNCTIONAL ANALYSIS OF THE CD166/ACTIVATED LEUKOCYTE CELL ADHESION MOLECULE (ALCAM) IN MEDULLOBLASTOMA
Authors: Takamune Achiha, Noriyuki Kijima, Naoki Kagawa, Chisato Yokota, Yasunori Fujimoto, Haruhiko Kishima
Journal: Neuro-Oncology (2018)

CD166/activated leukocyte cell adhesion molecule (CD166/ALCAM) is a transmembrane receptor, widely expressed in various tissues, and is involved in several functions such as cell adhesion, neurogenesis and angiogenesis. It was also reported that CD166/ALCAM expression was as a prognostic marker, and was related to stemness and invasion capacity in human cancer, including glioblastoma. However, CD166/ALCAM expression in medulloblastoma (MB) is not extensively studied. In this study, we investigated the expression and the biological roles of CD166/ALCAM in MB. For immunohistochemical analysis, 23 formalin-fixed paraffin-embedded (FFPE) MB samples from patients were analyzed. Five of 23 MBs (22%) were CD166/ALCAM positive, which showed diffuse or insular patterns. Four MB cell lines (Daoy, D341, D283, ONS-76) were analyzed for CD166/ALCAM expression by flow cytometry, and its expression ranged from high (Daoy) to low (D283). CD166/ALCAM knockdown by shRNAs decreased migration of Daoy cells in a wound healing assay. Furthermore, CD166/ALCAM knockdown Daoy cells tended to promote tumor cell invasion and dissemination when orthotopically transplanted in immuno-deficient mice. Our results showed distinct expression of CD166/ALCAM in MB and CD166/ALCAM is involved in MB cell migration and invasion.
RAS status in Algerian metastatic colorectal cancer
Authors: A. Bensalem
Journal: Annals of Oncology (2018)

Introduction: The identification of genetic anomalies within the cancerous cells today constitutes very valuable information to guide the diagnosis, the classification, the choice and the monitoring of the treatment for a growing number of cancers. Mutations in the gene RAS are found in meadows of half of the colorectal cancers and their research is therefore of paramount importance for the therapeutic care and the choice of a targeted therapy appropriate. Methods: It is a retrospective study, from records of patients followed in Medical Oncology Department, for a metastatic colorectal cancer, based on the study of bio molecular RAS status; from March 2016 to November 2017. 89 cases were collected; the parameters studied were: age, histological type, location, status NRAS, KRAS and the degree of tumor infiltration. Results: Of the 89 cases studied, the average age of discovery was 59 years old (40-77). The histological type adenocarcinoma represented 100% (n = 89) of cases. In 36.92% (n = 24) of the cases the localization was colic; 9.23% (n = 6) of cases were rectal and 3.06% (n = 2). The KRAS wild was in 51.68% (n = 46) of cases, in 19.10% (n = 17) at the level of exons 2, 3, 4 and at the level of the: codon 12 in 19.10% (n = 17), codon 13 in 17.97% (n = 16. The NRAS was wild in 46,06% (n = 41) of cases; in 17.97% (n = 16) at the level of exons 2, 3, 4 and posted in 3.37% (n = 3) of the cases, at the level of: the exon 2.4 in 2.24% (n = 2) and the exon 3 in 1.12% (n = 1).The average of the tumor infiltration was 66% (40% - 90%). The response to treatment was different (right versus left) and patients achieved treatment in more than 80% of cases. DISCUSSION: It is necessary to raise the percentage of the wild character at the beginning for the KRAS and the interest of the anti-EGFR. The development of the technique of the research of the NRAS has regained less wild suggesting that some of the non-responses to anti-EGFR are probably due to this difference in the determination of the Full RAS; deserving all the interest of the clinician in the support of adequate patients. Conclusion: The targeted therapies constitute a major evolution in digestive cancer. Before the effects very promising of these drugs, other molecules of the same therapeutic classes (anti-VEGF, anti EGFR) are in course of development and will probably to further the therapeutic effects.
Designing and implementing a curriculum for Sports and Exercise Medicine elective course for undergraduate medical students of Tehran University of Medical Sciences
Authors: Pardis Noormohammadpour, Farzin Halabchi, Reza Mazaheri, Mohammad Ali Mansournia, Zahra Alizadeh, Tohid Seif Barghi, Maryam Abolhasani, Ramin Kordi
Journal: British Journal of Sports Medicine (2018)

The addition of exercise prescription as a part of patient treatment to medical school curricula currently seems necessary due to the high rate of morbidity and mortality of non-communicable diseases (NCDs).1 Many studies have shown the importance of regular physical activity in preventing NCDs and their risk factors such as cardiovascular problems, diabetes, cancer, hypertension and obesity.2 Based on the World Health Organization (WHO)’s action plan, healthcare policies should be in line with increasing physical activity for all people.2 Physicians can play an important role in making this possible.3 Studies have shown, however, that graduate medical students are not well prepared to achieve this goal.4 5 Also, with an increase in athletes’ participation in recreational and professional sports activities, physicians can play a significant role in the management of athletes’ injuries.6 Therefore, creating an educational Sports and Exercise Medicine (SEM) curriculum for medical students is both helpful and necessary.

### Challenges ahead

Considering the variety of educational courses offered at medical school and students’ compact study schedule, finding the time, relevant content and experienced faculty members who can teach the syllabus of the SEM curriculum are all challenging. Harden has proposed 10 steps for planning and developing a curriculum (Harden’s 10 questions).7 Identification of needs and establishment of learning outcomes are the primary steps. It is expected that young doctors should be able to prescribe exercise and physical activity for the promotion of health and NCD prevention, and course evaluations should be defined based on these goals. Methods of content organisation and educational strategies should then be selected. Across the various proposed learning strategies, problem-based learning, integrated methods and elective programmes make it easier to reach the aforementioned goals. Professors can apply a range of teaching methods including lectures, study groups, slides, computers and simulators. For …
Smoking and prostate cancer risk in young men in Appalachian Kentucky.
Authors: Indraneel Gowdar, Priya Mallikarjun, Indraneel Reddy, Anjali Shankar, Mark Dignan
Journal: Journal of Clinical Oncology (2012)

e12004 Background: Kentucky has the highest smoking rates in the US, with 25.2% of the adult population considered current smokers compared to 18.4% nationwide (CRC, 2011 statistics), as well as high rates of chronic conditions including diabetes, heart disease, and lung cancer. In particular, the Appalachian area of Kentucky appears to have particularly high rates of both smoking and prostate cancer, beyond what is typical for the state as a whole. Recent data on prostate cancer from the Kentucky State Cancer Registry from 2004-2008 showed an incidence rate of 144 vs. 139.8 per 100,000 for "Appalachia" and Kentucky as a state, respectively. The purpose of this study is to investigate the relationship between smoking and risk of prostate cancer in Appalachian Kentucky. Methods: Data were collected on all prostate cancers diagnosed from 1996-2005 in a large hospital serving the Appalachian region. Data were collected without identifiers. Relevant statistics recorded included age at diagnosis, family history, and smoking status (classified as current smoker, non-smoker, or unknown smoking status). Results: A total of 286 patients with diagnosed prostate cancer were collected. The patients ranged from 45 to 94 years of age at diagnosis (Mean = 71, SD = 9.8). Of the 286, 89 (31.1%) had never smoked, and 94 (32.9%) were current or former cigarette smokers (Mean pack years = 25.4). To control for the age-related increase in cancer risk, patients were separated into two age groups: age 65 and younger (n=86, 30.1%), and older than 65 (n=200, 69.9%). The proportion of the younger group who smoked was significantly greater than that of the older group (44.2% vs. 28%, respectively; p= 0.009, Fischer's exact test). Conclusions: These data suggest that smoking in males younger than 65 is positively associated with an increased risk of prostate cancer in Appalachian Kentucky. Further study is needed to elucidate this relationship, as well as to evaluate any association between smoking severity and Gleason score.
Stable or fluctuating temperatures in winter: which is worse for your lungs?
Authors: Kin Bong Hubert Lam
Journal: Thorax (2018)

The ratification of the Paris Agreement in 20151 signifies a worldwide consensus on climate change has been reached. The Intergovernmental Panel on Climate Change has warned as global warming intensifies, extreme weather events (such as heat waves, droughts, floods) will become more frequent and more severe.2 Indeed in the UK, within the first few months of 2018, there has already been a cold wave between late February and early March (with maximum temperature 8°C–12°C below average for the time of year)3 and an unusually warm week in April (which saw a rise of almost 20°C from 6°C–7°C in the previous week).4 That heat waves or cold spells could lead to excess deaths has been documented in previous studies5–7 and is probably unquestionable. However, even in the absence of extreme temperature episodes, exposure to so-called non-optimum ambient temperatures has shown to be associated with elevated risks of morbidity and mortality.8–10 A recent study of over 74 million deaths from 13 countries has found most of the temperature-related short-term (days to weeks after the exposure) mortality displacement could in fact be attributed to moderate hot and cold temperatures, rather than extreme heat (temperature higher than 97.5th percentile) or cold (lower than 2.5th percentile).9 

Many of these previous studies have used mean daily temperature as the exposure metric. The fact that health impact has been observed in both colder and hotter temperatures suggests there is adaptation to usual temperatures and unexpected fluctuations in temperature may be more relevant. Temperature variability, as …
DEV-08. PEDIATRIC INTRA-MEDULLARY SPINAL CORD TUMORS AT CHILDREN’S CANCER HOSPITAL EGYPT; A SINGLE-CENTER 10-YEAR-EXPERIENCE
Authors: Moatasem El-Ayadi, Soha Abdel-Razek, Ahmed Elhemaly, Eslam Maher, Ayda Yousef, Mohamed El-Beltagy, Hala Taha
Journal: Neuro-Oncology (2018)

AIM: To evaluate intramedullary spinal cord tumors in pediatric patients regarding their clinical and radiological findings, histopathological diagnoses, therapeutic modalities and survival outcome. PATIENTS AND A total of 77 patients with intramedullary spinal tumors were diagnosed and treated at Children Cancer Hospital Egypt (CCHE-57357) between July 2007 and June 2017. Their medical records were reviewed for demographics, clinical, radiological and histopathological data, treatment received; chemotherapy, radiotherapy, surgical resection, as well as their treatment response, clinical events, and survival outcome. The median age was 5.35 years (range: 0.53 – 17.46 years; male/female ratio: 0.88). Commonest types were astrocytoma (n = 36, 46.8%) and ependymoma (n = 21, 27.3%). Overall, 80.6% of astrocytomas and 76.2% of ependymomas were low-grade. There was no correlation between tumor volume at presentation and histopathologic diagnosis. Seventy-two patients underwent surgery (gross-total resection (GTR), 22.2%; subtotal resection, 40.3%; biopsy, 37.5%). Extent of resection correlated significantly with histopathology, with GTR being more achieved with ependymoma (P-value <0.001). Fifty patients (65%) received chemotherapy while 34 patients (44.2%) received radiotherapy. The 5-year overall survival rate was 74.5%; and event-free survival rate was 69%. Only histopathological type correlated significantly with survival; embryonal tumors were negative prognostic factor for survival (P-value <0.001) while ependymomas were positive predictors of outcome (P-value < 0.05). Survival didn’t significantly differ with gender, age, nor extent of resection. Most pediatric spinal cord intramedullary tumors are low-grade tumors. Spinal ependymomas are amenable for GTR with favorable outcome. Surgery remains the main treatment in intramedullary spinal tumors.
LGG-51. METABOLIC PROFILING IN PEDIATRIC LOW GRADE GLIOMA IDENTIFIES GLUTATHIONE DEPLETION AFTER MTORC1 INHIBITION AND VALIDATES EVEROLIMUS AND CARBOPLATIN AS A POTENTIAL COMBINATION THERAPY
Authors: Brad Poore, Ming Yuan, Antje Arnold, Antionette Price, Jesse Alt, Jeffrey Rubens, Barbara Slusher, Charles Eberhart, Eric Raabe
Journal: Neuro-Oncology (2018)

The mTOR pathway contributes to the tumorigenicity of aggressive pediatric low grade glioma (pLGG) and TORC1 inhibitors have demonstrated efficacy in treating pLGG cell lines. The FDA-approved TORC1 inhibitor, everolimus, is currently in clinical trials for patients with recurrent/refractory pLGG. We hypothesized that metabolic alterations downstream of TORC1 inhibition could be targeted to synergize with everolimus and reduce pLGG tumorigenicity. We identified through unbiased metabolic screens and stable isotope tracing that glutathione was downregulated (p<0.001) after everolimus treatment in both in vitro and in vivo models of pLGGs. Based on this finding, we combined everolimus with carboplatin, a DNA damaging agent that is detoxified by glutathione conjugation. We treated 5 pLGG models (4 cell lines and one patient-derived xenograft) representing a range of mutations commonly found in pLGG including, BRAF-KIAA1549 fusion, BRAFV600E, and NF1 loss. To our knowledge, this study is the first to use a pLGG NF1 null cell line, JHH-NF1-PA1. Carboplatin synergized with everolimus to slow cell growth in most cell lines (CI<1 at Fa 0.5). The combination increased expression of apoptotic markers, (cleaved-PARP, cleaved caspase-3) and markers of DNA damage (phosphorylation of gamma-H2AX, 154%-1800% increase compared to carboplatin alone). The combination of carboplatin and everolimus reduced BRAFV600E-driven BT40 pLGG xenograft tumor growth better than either agent alone, (p<0.001 by ANOVA). Exogenous glutathione rescued the effects of everolimus, further supporting the mechanism of synergy between these agents. In summary, this study provides the pre-clinical justification for combining everolimus with carboplatin in pLGG clinical trials.
ACE2 as therapy for pulmonary arterial hypertension: the good outweighs the bad
Authors: Christophe Guignabert, Frances de Man, Marc Lombès
Journal: European Respiratory Journal (2018)

<b>Based on this highly encouraging clinical proof-of-concept, there is now a clear plan to explore interventions that stimulate the ACE2–Ang-(1–7)–Mas pathway further in large clinical trials</b>http://ow.ly/adXT30k1Z5h