tbuckley/cabot-search huggingface dataset:
Recent advances of biomimetic nano-systems in the diagnosis and treatment of tumor
Authors: Anning Li, Jiawei Zhao, Jingru Fu, Jia Cai, Peng Zhang
Journal: Asian Journal of Pharmaceutical Sciences (2019)

The lack of effective methods of diagnosis and treatment presents a major barrier to combat against tumor. The biomimetic concept is an emerging field that expresses great application potential in tumor fighting. Strategy for combining nano-systems with biomimetic technology has gained increasing attention that is proved bioinspired, environmentally benign, and promising. Herein, we provide an up-to-date review of biomimetic nano-systems as well as their applications in tumor therapy. In addition, the challenges and future directions of biomimetic nano-systems to achieve clinical translation are also pointed out.
Analysis of plasma-based <i>BRAF</i> and <i>NRAS</i> mutation detection in patients with stage III and IV melanoma.
Authors: David Polsky, Jyothirmayee S. Tadepalli, Shria Hafner, Gregory Chang, Nathaniel H. Fleming, Yongzhao Shao, Farbod Darvishian, Anna C. Pavlick, Russell S. Berman, Richard L. Shapiro, Iman Osman, Cynthia Spittle
Journal: Journal of Clinical Oncology (2013)

9023 Background: Patients with metastatic melanoma are eligible for BRAF inhibitor therapy if the BRAF V600E mutation can be identified in their tumor specimen. Patients lacking an available specimen for genotyping are unable to receive inhibitor therapy. We developed two mutation-specific genotyping platforms and tested their ability to detect BRAF and NRAS mutations in archived plasma and tumor samples to determine the potential utility of blood-based tumor genotyping in melanoma. Methods: We analyzed a group of 96 patients with stage III or IV melanoma, prospectively enrolled and followed in the NYU Melanoma Biorepository program. Each patient had a plasma sample and one or more tumor samples available for analysis. We used a combination of allele-specific PCR (Taqman) and SNaPshot assays to identify BRAF V600 and NRAS Q61 mutations in the tumor and plasma samples. Results: Among the 96 patients, 51 had stage III disease at the time of analysis; 45 had stage IV disease. Seventy-two patients had 2 or more tumor samples available for analysis, for a total of 204 tumors analyzed. In total, 52/96 (54%) patients had one or more BRAF or NRAS mutant tumors, including one patient with separate BRAF and NRAS mutant tumors (BRAF, n=35 (36%); NRAS, n=18 (19%)). We successfully amplified plasma DNA from 39/52 (75%) patients with tumor-associated mutations. Among those patients with amplifiable plasma DNA we detected mutations in 7 (18%) patients including 3 BRAF V600E, one V600K, 2 NRAS Q61K and one Q61L. Plasma-based mutations matched tumor-associated mutations in all 7 patients. All 7 patients had active disease at the time of blood draw. There were 32 patients with tumor-associated mutations in which a mutation could not be detected in the plasma. Only 15 of those 32 (47%) had active disease at the time of blood draw. There were no mutations detected in the plasma of the 44 patients whose tumors lacked BRAF or NRAS mutations. Conclusions: These data suggest that plasma-based detection of BRAF and NRAS mutations has a high specificity for tumor-associated mutations. It may prove to be a useful adjunct to tumor-based genotyping in patients with active disease, especially those lacking an available tumor specimen.
P14.27 The significance of multicentric noncontrast-enhancing lesions distant from surgically resected glioblastoma: Case series of 3 patients
Authors: J Hwang, H An, S Yoon, K Park
Journal: Neuro-Oncology (2019)

Abstract BACKGROUND Glioblastoma is the most malignant primary brain tumor. The tumor location and multiplicity plays an important role in surgical and further treatment. The incidence of multiple lesions at the time of diagnosis was known as 1–20%, which showed a poor prognostic factor. Most researches has focused on multiple contrast-enhancing lesions, however, multicentric non-enhancing lesions distant from glioblastoma has been rarely evaluated. The authors reported the case series of the patient who showed multicentric non contrast-enhancing lesions without connection to histologically-proven glioblastoma. MATERIAL AND METHODS Multicentric non contrast-enhancing lesions were defined as areas of FLAIR hyperintensity and mass effect without post-contrast enhancement, separated from the histologically-proven glioblastoma in a newly diagnosed disease. Three patients who showed distant non-enhancing lesions with appearance of a multicentric low-grade glioma were included in this study. The typical enhancing lesions were surgically resected and standard chemo-radiotherapy was followed in all patients. RESULTS All patients were male and their age was 38, 60 and 65 years old respectively. Multicentric tumor location was as follows: Case 1, left frontal lobe with non-enhancing lesion in left parahippocampal gyrus; Case 2, left parietal with non-enhancing lesion in left anteromedial temporal lobe; Case 3, left thalamus with non-enhancing lesions in both basal frontal and right temporal lobe. Pathologically, the resected enhancing tumor revealed glioblastoma in 2 patients and diffuse midline glioma in 1. All tumors were IDH-wild type. The resected enhanced lesion showed no progression but all non-enhancing lesions developed contrast-enhancing tumors at 3, 13 and 17 months after initial treatment, with high tracer uptake on 18FDG-PET or 18FDOPA-PET. Despite multidisciplinary treatment, two patients died from disease progression at 30 and 32 months after diagnosis and one patient is still alive with overall survival of 15 months. CONCLUSION The appearance of multicentric non-enhancing lesions distant from a typically enhancing tumor showed an uncommon finding in glioblastoma and poor prognostic features. These lesions progress faster than expected for a low-grade glioma. These lesions should be distinguished from typical low-grade glioma and should be considered more advanced lesions than their appearances suggest.
Efficacy and safety of oral etoposide maintenance therapy following cisplatin plus etoposide in advanced small cell lung cancers (Study of the Anatolian Society of Medical Oncology).
Authors: Zuhat Urakci, Muhammet Ali Kaplan, Olcun Umit Unal, Mehmet Kucukoner, Alper Sevinc, Ilhan Oztop, Ali Suner, Tulay Eren, Mevlude Inanc, Dogan Koca, Omer Kamil Yazici, Abdurrahman Isikdogan
Journal: Journal of Clinical Oncology (2013)

e18546 Background: Small cell lung cancers (SCLC) constitute a mean of 15% of lung cancers and present with advanced disease at time of diagnosis in 60% of cases. Cisplatin plus etoposide schedule is the standard treatment in these patients , whereas the role of maintenance therapy is debated. We assessed the efficacy and safety of oral etoposide maintenance therapy following cisplatin plus etoposide in advanced SCLC. Methods: Demographic features, treatment response, survival rate, and toxicity rate were assessed in our patients who were followed up for advanced SCLC between 2006 and 2012, had a ECOG performance status of 0-1, and were given oral etoposide maintenance therapy (50mg/day, given 14 days of a 21-day cycle, a total of 6 cycles) following 6 courses of cisplatin (75 mg/m 2 , 1 day) and etoposide (100mg/m 2 , 3 days). Results: A total of 51 patients were studied, 46 (90.2%) of whom were male; the mean age was 59 (28-78) years at diagnosis. Forty-four (86.2%) patients had partial remission while 7 (13.7%) had complete remission. Nine (17.6%) developed neutropenic fever while grade 3-4 toxicities, neutropenia, anemia, thrombocytopenia, neuropathy, diarrhea, nausea and vomiting were present in 39.2%, 9.8%, 5.9%, 1.9%, 3.9%, 3.9%, and 1.9% respectively. Chemotherapy was postponed in fourteen (27.4%) patients due to toxicity. Six (11.7%) patients taking oral etoposide developed febrile neutropenia and 3 (5.9%) developed grade 3-4 thrombocytopenia. Chemotherapy was postponed in 5 (9.8%) patients due to toxicity while no toxic death was observed. After a median follow-up of 19 months, 32 (62.7%) patients experienced progression of disease and 29 (56.8%) died. Median progression free survival was found 11.6 months (%95 CI; 10.2-12.9 months) and median overall survival was found 15.6 (%95CI; 11.5-19.7 months) months. Conclusions: Our results were similar with the previous literature. Oral etoposide maintenance therapy following cisplatin plus etoposide therapy in advanced SCLC is effective and tolerable. Further randomized studies are needed in this topic.
Prediction and Treatment of Radiation Enteropathy: Can Intestinal Bugs Lead the Way?
Authors: Suk Yee Lam, Maikel P. Peppelenbosch, Gwenny M. Fuhler
Journal: Clinical Cancer Research (2019)

Radiation-induced gastrointestinal toxicity is a significant comorbidity affecting many patients with cancer. Intestinal microbial changes are observed in patients suffering from radiation enteropathy, although a causal relationship with disease activity has yet to be proven. Implementation of bacterial profiling in clinical care could improve recognition and management of this debilitating disease.See related article by Reis Ferreira et al., p. 6487.
Effects of Individual Placement and Support Supplemented With Cognitive Remediation and Work-Focused Social Skills Training for People With Severe Mental Illness
Authors: Thomas Nordahl Christensen, Iben Gammelgård Wallstrøm, Elsebeth Stenager, Anders Bo Bojesen, Christian Gluud, Merete Nordentoft, Lene Falgaard Eplov
Journal: JAMA Psychiatry (2019)

Individual placement and support (IPS) seems to be an effective vocational intervention for people with severe mental illness, but its effects have not yet been shown in the Danish welfare model. Also, effects may be enhanced by adding cognitive remediation and work-focused social skills training (IPS with enhancements [IPSE]).To investigate the effects of IPS vs IPSE vs service as usual (SAU) on a population of individuals with severe mental illness in Denmark.This was an investigator-initiated, 3-group, parallel, assessor-blinded randomized clinical trial that used early-intervention teams or community mental health services in 3 Danish cities to recruit participants with severe mental illness. Participants were randomly assigned to receive IPS, IPSE, or SAU from November 2012 to February 2016, and follow-up continued until August 2017.Participants allocated to the IPS intervention received vocational support per the principles of the IPS model. Participants in the IPSE arm received cognitive remediation and social skills training in addition to IPS. The group receiving SAU received vocational rehabilitation at the Danish job centers.The primary outcome was the number of hours in competitive employment or education during the 18-month follow-up. Secondary outcomes included intergroup differences in employment or education at any point during follow-up; time to employment or education; and cognitive and social functioning, self-esteem, and self-efficacy.Of the 720 included participants (mean [SD] age, 32.8 [9.9] years; 276 [38.3%] women), 243 received IPS, 238 received IPSE, and 239 received SAU. Most participants (551 [76.5%]) were diagnosed with a schizophrenia spectrum disorder. During the 18-month follow-up, the IPSE group worked or studied a mean (SD) of 488.1 (735.6) hours, compared with 340.8 (573.8) hours in the group receiving SAU (success-rate difference [SRD], 0.151 [95% CI, 0.01-0.295]; P = .016). The mean (SD) in the IPS group was 411 (656.9) (SRD, 0.127 [95% CI, -0.017 to 0.276]; P = .004). There was no difference between IPS and IPSE in any vocational outcomes, and the 3 groups showed no differences in any nonvocational outcomes, except that the IPS and IPSE groups were more satisfied with the services received than the group receiving SAU (IPS vs SAU: SRD, 0.310 [95% CI, 0.167-0.445]); IPSE vs SAU: SRD, 0.341 [95% CI, 0.187-0.478]).Compared with SAU, IPS and IPSE seem to be viable routes to increase employment and education rates in people with severe mental illness in Denmark, but no additional effects were observed by enhancing IPS.ClinicalTrials.gov identifier: NCT01722344.
Abstract 19485: Migrant South Asian Women Have Increased Arterial Stiffness Compared to Black and White Women Residing in the United States
Authors: Danny J Eapen, Pankaj Manocha, Riyaz Patel, Shafaat Ali Khan, Vivek Menon, Hatem Al Kassem, Mohammad Hammadah, Ayman Samman Tahhan, Nima Ghasemzadeh, Mohamed Khayata, Mohammad Tarek Kabbany, Mohammad Asfari, Amr Mohamed Rashed Mohamed, Ashraf Khuram, Neal Bhatia, Naveen Bellam, Salman Sher, Uzair Janjua, Meera Shah, Ying X Liu, Laurence Sperling, Arshed Quyyumi
Journal: Circulation (2012)

Introduction: Death from cardiovascular disease (CVD) is proportionally higher in Black and South Asians (SA) residing in the United States (U.S.) compared to their White counterparts. While all other sex- ethnic groups demonstrated a decline in all cause and CVD mortality, it has recently been shown that Asian Indian women residing in the U.S. experienced an increase. Arterial Stiffness indices, such as Augmentation Index, have been associated with CVD in western populations. We hypothesized that, in a community setting, migrant SA Women in the U.S. have a greater degree of arterial stiffness than do their Black (BW) and White Women (WW) counterparts. Methods: We studied 697 volunteers residing in the metro Atlanta area from 2006-2010 that include 263 SA women (age 49±12 years), 140 BW (age 46±10 years), and 294 WW (age 48±10 years). Using radial artery tonometry (Sphygmocor©, Atcor) we calculated Augmentation Index Adjusted for heart rate (AIX) as a surrogate measure of arterial stiffness. Anthropometric, clinical and lipid levels were assessed. Women were studied as a whole and a subset of women free of traditional CVD risk factors were analyzed separately. Univariate and multivariate regression models adjusted for age, race, BMI, hypertension, diabetes, dyslipidemia, smoking status, and lipid levels were performed. Results: SA women had a greater AIX compared to their BW and WW counterparts respectively (32 vs 25 vs 23, p&lt;0.001). BMI was lowest in SA Women followed by WW and BW respectively (26.7 vs 26.8 vs 31.7, p&lt;0.001). There was a similar amount of hypertension (18%) and dyslipidemia (6%) in SA women but more diabetes (23%) compared to WW (17%, 22%, 5%) and BW (29%, 16%, 6%) (p&lt;0.001 for all). In the subset of women free of CVD risk factors, SA women still had a greater degree of arterial stiffness compared to their BW and WW counterparts (31 vs 24 vs 22, p&lt;0.001). In the entire cohort and in the subset of women free of traditional CVD risk factors, LDL, age and race (p&lt;0.001 for both groups) were significant independent predictors of AIX. Conclusions: Community dwelling migrant SA women have a significantly greater degree of arterial stiffness compared to their WW and BW counterparts despite having similar traditional CVD risk factors.
Altered Gene Expression along the Glycolysis–Cholesterol Synthesis Axis Is Associated with Outcome in Pancreatic Cancer
Authors: Joanna M. Karasinska, James T. Topham, Steve E. Kalloger, Gun Ho Jang, Robert E. Denroche, Luka Culibrk, Laura M. Williamson, Hui-Li Wong, Michael K.C. Lee, Grainne M. O'Kane, Richard A. Moore, Andrew J. Mungall, Malcolm J. Moore, Cassia Warren, Andrew Metcalfe, Faiyaz Notta, Jennifer J. Knox, Steven Gallinger, Janessa Laskin, Marco A. Marra, Steven J.M. Jones, Daniel J. Renouf, David F. Schaeffer
Journal: Clinical Cancer Research (2019)

Identification of clinically actionable molecular subtypes of pancreatic ductal adenocarcinoma (PDAC) is key to improving patient outcome. Intertumoral metabolic heterogeneity contributes to cancer survival and the balance between distinct metabolic pathways may influence PDAC outcome. We hypothesized that PDAC can be stratified into prognostic metabolic subgroups based on alterations in the expression of genes involved in glycolysis and cholesterol synthesis.We performed bioinformatics analysis of genomic, transcriptomic, and clinical data in an integrated cohort of 325 resectable and nonresectable PDAC. The resectable datasets included retrospective The Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC) cohorts. The nonresectable PDAC cohort studies included prospective COMPASS, PanGen, and BC Cancer Personalized OncoGenomics program (POG).On the basis of the median normalized expression of glycolytic and cholesterogenic genes, four subgroups were identified: quiescent, glycolytic, cholesterogenic, and mixed. Glycolytic tumors were associated with the shortest median survival in resectable (log-rank test P = 0.018) and metastatic settings (log-rank test P = 0.027). Patients with cholesterogenic tumors had the longest median survival. KRAS and MYC-amplified tumors had higher expression of glycolytic genes than tumors with normal or lost copies of the oncogenes (Wilcoxon rank sum test P = 0.015). Glycolytic tumors had the lowest expression of mitochondrial pyruvate carriers MPC1 and MPC2. Glycolytic and cholesterogenic gene expression correlated with the expression of prognostic PDAC subtype classifier genes.Metabolic classification specific to glycolytic and cholesterogenic pathways provides novel biological insight into previously established PDAC subtypes and may help develop personalized therapies targeting unique tumor metabolic profiles.See related commentary by Mehla and Singh, p. 6.
Evolving Priorities for Imaging Utilization Research
Authors: Deborah Levine, Richard Duszak
Journal: JAMA (2019)

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 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) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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
Systemic delivery of a Gli inhibitor via polymeric nanocarriers inhibits tumor-induced bone disease
Authors: Joseph P. Vanderburgh, Kristin A. Kwakwa, Thomas A. Werfel, Alyssa R. Merkel, Mukesh K. Gupta, Rachelle W. Johnson, Scott A. Guelcher, Craig L. Duvall, Julie A. Rhoades
Journal: Journal of Controlled Release (2019)
A Phase I Study of the Combination of Rituximab and Ipilimumab in Patients with Relapsed/Refractory B-Cell Lymphoma
Authors: Joseph M. Tuscano, Emanual Maverakis, Susan Groshen, Denice Tsao-Wei, Guillaume Luxardi, Alexander A. Merleev, Anne Beaven, John F. DiPersio, Leslie Popplewell, Robert Chen, Mark Kirschbaum, Mark A. Schroeder, Edward M. Newman
Journal: Clinical Cancer Research (2019)

Based on the potential for ipilimumab (I) to augment T-cell activation, we hypothesize that ipilimumab would augment the efficacy of rituximab (R) in patients with relapsed/refractory (R/R) CD20+non-Hodgkin's lymphoma (NHL). This phase I study aimed to identify a recommended phase 2 dose, document toxicities, and preliminarily assess efficacy and potential predictive biomarkers.Thirty-three patients with R/R CD20+B-cell lymphoma received R at 375 mg/m2weekly for 4 weeks and I at 3 mg/kg on day 1 and every 3 weeks for four doses. Responding patients went on to maintenance with each agent given every 12 weeks. To facilitate correlative analysis, the expansion phase randomized patients to simultaneous R+I versus R with I delayed 2 weeks.Toxicity was manageable; no dose-limiting toxicity was observed at the doses studied. When considering the entire cohort, efficacy was modest, with an objective response rate (ORR) of 24% and median progression-free survival (PFS) of 2.6 months. However, in follicular lymphoma patients, the ORR was 58% with a median PFS of 5.6 months. The randomized comparison of R with R+I demonstrated that R+I resulted in more effective B-cell depletion (BCD). Both B-cell depletion and the ratio of CD45RA-regulatory T cell (Treg) to Treg were associated with response at all time points.The combination of R+I has manageable toxicity and encouraging efficacy in R/R follicular lymphoma. The ratio of CD45RA-Tregs to total Tregs, and peripheral BCD should be studied further as potential predictors of response.
Beyond the synucleinopathies: alpha synuclein as a driving force in neurodegenerative comorbidities
Authors: Naomi P. Visanji, Anthony E. Lang, Gabor G. Kovacs
Journal: Translational Neurodegeneration (2019)

The fundamental role that alpha-synuclein (aSyn) plays in the pathogenesis of neurodegenerative synucleinopathies, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy, is a well-accepted fact. A wealth of experimental evidence has linked this relatively small but ubiquitously expressed protein to a plethora of cytopathologic mechanisms and suggests that aSyn may be capable of seeding the progressive spread of synucleinopathy throughout the brain. Beyond the synucleinopathies, the abnormal deposition of aSyn is frequently seen in a variety of other neurodegenerative proteinopathies including Alzheimer's disease. In spite of the fact that the frequency of concomitant aSyn pathology in these disorders is such that it can be considered the rule rather than the exception, the potential role that aSyn may have in these disorders has received relatively little attention. In this article we postulate that aSyn may in fact be a key protein in driving the pathogenic processes in neurodegenerative comorbidities. In addition to reviewing the frequency of concomitant deposition of aSyn in the neurodegenerative proteinopathies, we also consider our current understanding of the interaction of aSyn with other neurodegenerative disease-associated proteins, including tau, TDP-43, amyloid-β and prion protein, in the context of neuropathologic studies describing the anatomical sites of potential concomitant pathology. We conclude that a growing body of evidence, encompassing neuropathology studies in human brain, animal models of concomitant proteinopathies and studies employing sophisticated methods of probing protein-protein interaction, cumulatively suggest that aSyn is well positioned to exert a strong influence on the pathogenesis of the neurodegenerative comorbidities. We hope to stimulate research in this emerging field and consider that future studies exploring the contribution of aSyn to the pathogenic processes in neurodegenerative comorbidities may provide critical information pertaining to diagnosis and the development of vital disease modifying treatments for these devastating diseases.