tbuckley/cabot-search huggingface dataset:
GERM-12. PITUITARY FAILURES IN CNS MIXED MALIGNANT GERM CELL TUMORS (MMGCTs). EXPERIENCE GENERATED IN SIOP CNS GCT 96
Authors: Christian Asmus Kuhrt, Rolf Dieter Kortmann, Didier Frappaz, Frank Saran, Maria Luisa Garre, Jans-Enno Müller, Umberto Ricardi, Thomas Czech, Claire Alapetite, James C Nicholson, Gabriele Calaminus
Journal: Neuro-Oncology (2018)

CNS MMGCTs are treated with a combination of chemotherapy and irradiation. In SIOP CNS GCT 96 radiotherapy (RT) doses given for local tumor control were 54 Gy. In cases with dissemination 30 Gy craniospinal RT was applied. We therefore examined the presence of pituitary failures in respect to RT dose to the pituitary region. We evaluated 149 patients treated between 10/96 and 31/12/2005; 86/149 patients were treated according to protocol, were alive and had no recurrence at the time of follow up in November 2009 (69 male, 17 female: mean age 14 years, observation time median 6.5 years). 30/86 patients had pituitary failure, of which 1 showed diabetes insipidus only, 16 had anterior pituitary failure only and 13 both. 18 of the 30 had no anterior pituitary failure at diagnosis, but only at follow-up. 10 of 86 patients had a prescription RT dose of 30 Gy and 43 had 0 Gy to the pituitary area; of these 53, 10 had pituitary failures at follow-up. 20/33 patients who received 54 Gy to the pituitary area showed anterior pituitary failure. Pituitary failures are a major long-term risk of CNS MMGCTs. 60% of patients treated with 54 Gy prescribed RT dose to pituitary area, had anterior pituitary failure at follow-up, compared with 19% treated with 0/30 Gy. Reduction of RT dose to pituitary area where possible should be an aim of future treatment strategies for MMGCTs. (supported in part by German Cancer Aid)
MBCL-41. TREATMENT FAILURE PATTERNS ACROSS MEDULLOBLASTOMA SUBGROUPS WITHIN A PROSPECTIVE PHASE II CLINICAL TRIAL OF RISK-ADAPTED, VOLUME-REDUCED RADIATION THERAPY AND DOSE-INTENSE CHEMOTHERAPY WITH STEM CELL SUPPORT
Authors: Christopher Tinkle, John Lucas, Sudharsan Srinivasan, Parker Tumlin, Arzu Onar-Thomas, Jie Huang, Zoltan Patay, David Ellison, Brent Orr, Paul Northcott, Giles Robinson, Amar Gajjar, Thomas Merchant
Journal: Neuro-Oncology (2018)

To characterize the patterns of progression across medulloblastoma (MB) clinical risk and molecular subgroups. METHODS AND 155 pediatric patients with newly diagnosed MB were treated at our institution on a prospective, multi-center phase II trial of adjuvant RT and dose-intense chemotherapy with autologous stem cell transplant. RT included CSI to 23.4 Gy (average risk, AR) or 36-39.6 Gy (high risk, HR) followed by conformal primary site RT with a 1 cm clinical target volume to a cumulative dose of 55.8 Gy. MB subgroup was determined using 450K DNA methylation. Progression was classified by anatomic site (primary site failure (PSF) +/- distant failure (DF), or isolated DF), and RT dosimetry. 32 patients have progressed (median follow-up 9.0 years (range, 0.3 - 14.2 y)). Anatomic failure pattern differed by clinical risk (P=0.0054) and methylation subgroup (P=0.0001). 10-year cumulative incidence (CI) of PSF was 6.2% and 5.6% in AR and HR patients, respectively (P=0.92), and did not differ across subgroups (P=0.16). 10-year CI of DF was 8.2% vs. 28.1% for AR vs. HR (P=0.0007); and 0% for WNT, 18.4% for SHH, 39.5% for G3, and 6.4% for G4 (P<0.0001). Of 9 patients with PSF, 8 were within the primary site RT field and 4 represented SHH tumors. The low incidence of PSF between clinical risk groups following conformal primary site RT is comparable to prior studies using larger primary site or posterior fossa boost volumes. Distinct anatomic failure patterns across MB subgroups suggest subgroup-specific treatment strategies should be considered.
Strategies to Prevent Obesity-Related Cancer
Authors: Yijun Chen, Erik Dutson, Guido Eibl
Journal: JAMA (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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Impact of HIF-1alpha and PKM1 expression on acquisition of paclitaxel resistance in gastric cancer
Authors: S. Fushida, M. Okazaki, J. Kinoshita, T. Yamaguchi, T. Ohta
Journal: Annals of Oncology (2018)

Introduction: In gastric cancer patients, one of the greatest obstacles to effective chemotherapy is the development of chemoresistance. It has been previously noted that HIF-1α was concerned with chemoresistance acquisition, and it was recently noted about the association of PKM1 and chemoresistance. The purpose of this study was to identify the effect of HIF-1α and PKM1 expression in leading to acquired chemoresistance using established paclitaxel-resistant gastric cancer cell line. Methods: Cancer cell line resistant to paclitaxel was established from MKN45 by stepwise exposure. The expressions of HIF-1α, apoptosis, VEGF, multidrug transporters and glycolytic enzyme were examined by western blotting, ELISA and Immunohistochemistry. We also assessed the tumor proliferation by subcutaneous tumor and peritoneal dissemination of mouse xenograft model. Results: The resistance index (RI) was 6.1 by determining as the ratio of the IC50 of rMKN45-PTX / IC50 of MKN45. Expression of NF-kB and HIF-1α was increased in rMKN45-PTX compared with those in the parent cells. Expressions of Bax and caspase-3 were significantly downregulated in rMKN45-PTX (p<0.05). In contrast, an increased expression of Bcl-xL, P-gp, MRP, and VEGF (2200 pg/ml) was observed in rMKN45-PTX. The expression level of PKM1 was 2 times up-regulated in rMKN45-PTX (p<0.05), on the other hand, PKM2 was almost similar to MKN45. We demonstrated that mouse subcutaneous tumors derived from rMKN45-PTX were significantly larger than those from MKN45 cells (1450 mm3 vs 750 mm3, p<0.05). Peritoneal dissemination model of rMKN45-PTX also showed larger than those of MKN45 (0.8 g/16 nodules vs 0.4 g/7 nodules, p<0.05). HIF-1α was key molecular of chemoresistance acquisition, which might be impacted the angiogenesis, cell proliferation, anti-apoptosis and multidrug transporter. Furthermore, PKM1 might be important molecular in chemoresistance acquisition. Conclusion: Under the stress of chemotherapeutic agent exposure, high expression of HIF-1α affects downstream various genes. Although the underlying mechanism is unknown, our data suggest that PKM1 is also a molecular target for gastric cancer treatment.
NSRG-06. BRAIN METASTASIS IN WILMS’ TUMOR: A CASE REPORT
Authors: Mehdi Borni, Anis Abdelhedi, Fatma Kolsi, Brahim Kammoun, Mohammed Zaher Boudawara
Journal: Neuro-Oncology (2018)

In children with solid tumors, brain metastasis is relatively uncommon, accounting for only 0.5-1.8% of all pediatric craniocerebral tumors. Wilms’ tumor is the most common abdominal tumor of childhood, and its cerebral metastasis is apparently very rare. We report the case of a 10-year-old boy underwent left nephrectomy for Wilms’ tumor with pulmonary and hepatic metastasis. Treatment after complete resection of the tumor included chemotherapy and radiotherapy. He was referred to our Neurosurgery department six months after initial diagnosis. He complained of frontal headache of increasing severity associated with weightiness in the left hemibody. On admission, his state of consciousness was found to be decreased and he had a left hemiplegia. A cranial computed tomography scan and a cerebral MRI were performed immediately showed an isodense mass in the right frontoparietal region with very little edema. After an intravenous injection of contrast medium there was marked homogenous enhancement of the lesion. A subsequent craniotomy was performed with removal of the neoplasm. Histopathological examination confirmed that it was a metastatic Wilms’ tumor. After the operation, the patient was treated with radiotherapy directed to the whole brain, and additional courses of chemotherapy were given. On a follow up examination 3 month later, the patient remained clinically stable.
Metformin exposure in first trimester of pregnancy and risk of all or specific congenital anomalies: exploratory case-control study
Authors: Joanne E Given, Maria Loane, Ester Garne, Marie-Claude Addor, Marian Bakker, Bénédicte Bertaut-Nativel, Miriam Gatt, Kari Klungsoyr, Nathalie Lelong, Margery Morgan, Amanda J Neville, Anna Pierini, Anke Rissmann, Helen Dolk
Journal: BMJ (2018)

<h3>Abstract</h3> <h3>Objective</h3> To investigate whether exposure to metformin during the first trimester of pregnancy, for diabetes or other indications, increases the risk of all or specific congenital anomalies. <h3>Design</h3> Population based exploratory case-control study using malformed controls. Cases of 29 specific subgroups of non-genetic anomalies, and all non-genetic anomalies combined, were compared with controls (all other non-genetic anomalies or genetic syndromes). <h3>Setting</h3> 11 EUROmediCAT European congenital anomaly registries surveying 1 892 482 births in Europe between 2006 and 2013. <h3>Participants</h3> 50 167 babies affected by congenital anomaly (41 242 non-genetic and 8925 genetic) including live births, fetal deaths from 20 weeks' gestation, and terminations of pregnancy for fetal anomaly. <h3>Main outcome measure</h3> Odds ratios adjusted for maternal age, registry, multiple birth, and maternal diabetes status. <h3>Results</h3> 168 babies affected by congenital anomaly (141 non-genetic and 27 genetic) were exposed to metformin, 3.3 per 1000 births. No evidence was found for a higher proportion of exposure to metformin during the first trimester among babies with all non-genetic anomalies combined compared with genetic controls (adjusted odds ratio 0.84, 95% confidence interval 0.55 to 1.30). The only significant result was for pulmonary valve atresia (adjusted odds ratio 3.54, 1.05 to 12.00, compared with non-genetic controls; 2.86, 0.79 to 10.30, compared with genetic controls). <h3>Conclusions</h3> No evidence was found for an increased risk of all non-genetic congenital anomalies combined following exposure to metformin during the first trimester, and the one significant association was no more than would be expected by chance. Further surveillance is needed to increase sample size and follow up the cardiac signal, but these findings are reassuring given the increasing use of metformin in pregnancy.
Distinguishing Mild, Moderate, and Severe Hidradenitis Suppurativa
Authors: Georgios Kokolakis, Robert Sabat
Journal: JAMA Dermatology (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 Dermatology 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 Dermatology journal
QOL-15. VISUAL IMPAIRMENT AND AUDITORY COMPENSATION IN CHILDREN TREATED FOR OPTIC PATHWAY GLIOMA
Authors: Chiara Papini, Nicola Pitchford, Rob Dineen, David Walker
Journal: Neuro-Oncology (2018)

Survivors of paediatric Optic Pathway Glioma (OPG) experience varying degrees of visual impairment. Yet sparse research has examined the impact of brain damage and the resulting vision loss on cognitive development and scholastic progression, and to date, no studies have investigated potential compensatory mechanisms and strategies in auditory functioning, as is reported in visually impaired individuals. This study describes the motor, cognitive, and scholastic abilities in a cohort of 12 children, aged 6-13 years, diagnosed with OPG and treated with observation and/or chemotherapy. Analogous tasks that rely on either visual or auditory input were used to assess core skills, including fine motor coordination, attention, memory, spoken English comprehension, and mathematics. Results showed no significant difference between visual and auditory performance across abilities. Only visual and auditory performance of the two scholastic abilities were associated, suggesting that a common mechanism might underpin complex capabilities crucial for school performance irrespective of the sensory modality of the task, while different visual and auditory neural processes could sustain specific motor and cognitive skills. Visual acuity in the best eye did not correlate with performance in visually-based behavioural tasks, suggesting no direct association between low-level sensorial experience and high-level cognition in the visual domain. Overall, these results demonstrate no evident compensation for the vision loss through the auditory channel and highlight the importance of including multiple sensory modalities in the neuropsychological follow-up assessment for these children. These results need to be corroborated with a larger sample of paediatric patients for generalisation at a population level.
The Burden of Bereavement: Early-Onset Depression and Impairment in Youths Bereaved by Sudden Parental Death in a 7-Year Prospective Study
Authors: Steven Pham, Giovanna Porta, Candice Biernesser, Monica Walker Payne, Satish Iyengar, Nadine Melhem, David A. Brent
Journal: American Journal of Psychiatry (2018)

The authors sought to determine the long-term impact of sudden parental death on youths and pathways between youth bereavement and impairment.
HGG-10. THE PI3K/mTOR PATHWAY CONTRIBUTES TO SEX DIFFERENCES IN GLIOBLASTOMA
Authors: Jasmin Sponagel, Kwanha Yu, Joseph Ippolito, Benjamin Deneen, Josh Rubin
Journal: Neuro-Oncology (2018)

Glioblastoma (GBM) occurs more commonly in males but female GBM patients survive significantly longer. In our efforts to identify the mechanisms underlying these differences, we found that EGFR amplification and increased mTOR phosphorylation worsen outcome for male, but not female patients. In order to investigate the contribution of the PI3K/mTOR pathway to sex differences in GBM, we used a murine model of GBM with inactivation of Neurofibromin 1 and p53 function. This model has previously yielded important insights into sexual dimorphism in GBM. When we activated the pathway in this model through PTEN depletion, we abrogated the sex differences. In a complimentary manner, when we inhibited this pathway with targeted drugs, we increased the sex differences. Thus, we hypothesized that the PI3K/mTOR pathway is sexually dimorphic in GBM. In support of this, we found greater activation of downstream mediators in male GBM cells upon treatment with EGF, insulin or IGF-1. A major mechanism by which the PI3K/mTOR pathway regulates GBM cell growth is through the regulation of glucose metabolism. We performed a metabolic screen of male and female murine GBM cells treated either with insulin or vehicle. Multiple central carbon metabolites, involved in glycolysis, nucleotide metabolism, and the TCA cycle, were significantly different in male and female cells. Together, these data indicate that the PI3K/mTOR pathway and its metabolic targets are sexually dimorphic in GBM. This dimorphism may contribute to sex differences in GBM incidence and outcome.
Estimating and Interpreting the Overall Survival Benefit of Checkpoint Inhibitors via Meta-analysis
Authors: Hajime Uno, Lu Tian, Lee-Jen Wei
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
<scp>JAK</scp>‐1 Inhibition Suppresses Interferon‐Induced <scp>BAFF</scp> Production in Human Salivary Gland
Authors: Jaeseon Lee, Jennifer Lee, Seung‐Ki Kwok, SeungYe Baek, Se Gwang Jang, Seung‐Min Hong, Jae‐Woong Min, Sun Shim Choi, Juhyun Lee, Mi‐La Cho, Sung‐Hwan Park
Journal: Arthritis & Rheumatology (2018)

Objective To examine whether a JAK inhibitor regulates functional responses of human salivary gland epithelial cells ( SGEC s) and disease parameters in an animal model of Sjögren's syndrome ( SS ). Methods Common differentially expressed genes ( DEG s) were analyzed among peripheral blood mononuclear cells from patients with primary SS and other data sets, using blood and SG tissue. Validation of expression in SG s was analyzed by focus score. Inhibition of messenger RNA expression of DEG s and BAFF by filgotinib was analyzed using reverse transcription–polymerase chain reaction in primary SGEC s. SG organoid cultures were used to determine the association between DEG s and BAFF via knockdown using small interfering RNA s or to determine regulation of BAFF by JAK inhibitor. Filgotinib (1.5 mg/kg) was intraperitoneally injected into 8‐week‐old NOD /ShiLtJ mice 3 times per week to analyze manifestations of disease. Finally, STAT signaling was assessed in human and mouse SGEC s. Results Expression of the DEG s IFNG and BAFF increased in SG s from patients with primary SS , as assessed by focus score. There was a significant correlation between IFIT 2 and BAFF expression. JAK inhibitor suppressed interferon ( IFN )–induced transcription of DEG s and BAFF in human primary SGEC s. Knockdown of DEG s or inhibition of JAK caused reduced secretion of BAFF in human SG organoid cultures. In addition, filgotinib‐treated mice exhibited increased salivary flow rates and marked reductions in lymphocytic infiltration of SG s. JAK inhibitor regulated IFN α‐ and IFN γ‐induced pSTAT ‐1 Y701 , pSTAT ‐3 Y705 , and protein inhibitor of activated STAT ‐3 ( PIAS ‐3) in human SGEC s as well as IFN γ‐induced pSTAT ‐1 Y701 , pSTAT ‐3 S727 , and PIAS ‐1 in mouse SGECs. Conclusion JAK inhibition controls aberrant activation of SGEC s and may be a novel therapeutic approach for primary SS .
Hypogonadotropic Hypogonadism in Men With Diabesity
Authors: Sandeep Dhindsa, Husam Ghanim, Manav Batra, Paresh Dandona
Journal: Diabetes Care (2018)

One-third of men with obesity or type 2 diabetes have subnormal free testosterone concentrations. The lower free testosterone concentrations are observed in obese men at all ages, including adolescents at completion of puberty. The gonadotropin concentrations in these males are inappropriately normal; thus, these patients have hypogonadotropic hypogonadism (HH). The causative mechanism of diabesity-induced HH is yet to be defined but is likely multifactorial. Decreased insulin and leptin signaling in the central nervous system are probably significant contributors. Contrary to popular belief, estrogen concentrations are lower in men with HH. Men with diabesity and HH have more fat mass and are more insulin resistant than eugonadal men. In addition, they have a high prevalence of anemia and higher mortality rates than eugonadal men. Testosterone replacement therapy results in a loss of fat mass, gain in lean mass, and increase in insulin sensitivity in men with diabesity and HH. This is accompanied by an increase in insulin-signaling genes in adipose tissue and a reduction in inflammatory mediators that interfere with insulin signaling. There is also an improvement in sexual symptoms, anemia, LDL cholesterol, and lipoprotein (a). However, testosterone therapy does not consistently affect HbA1c in men with diabetes. The effect of testosterone replacement on cardiovascular events or mortality in men with diabesity is not known and remains to be studied in prospective trials.
Treatment of IgM-associated immunoglobulin light-chain amyloidosis with rituximab-bendamustine
Authors: Richa Manwani, Sajitha Sachchithanantham, Shameem Mahmood, Darren Foard, Faye Sharpley, Tamer Rezk, Thirusha Lane, Cristina Quarta, Marianna Fontana, Helen J. Lachmann, Julian D. Gillmore, Carol Whelan, Philip N. Hawkins, Ashutosh D. Wechalekar
Journal: Blood (2018)