tbuckley/cabot-search huggingface dataset:
Abstract MIP-047: INHIBITION OF POLY ADP–RIBOSE POLYMERASE (PARP) IN OVARIAN CANCER CELLS ENRICHES FOR CD133 AND CD117 POSITIVE POPULATIONS
Authors: Chiara Bellio, Rosemary Foster, Whitfield B. Growdon, Panagiotis Konstantinopoulos, Bo R. Rueda
Journal: Clinical Cancer Research (2017)

Abstract Keywords: chemoresistance, cancer stem cells (CSC), DNA repair pathways, PARP inhibition INTRODUCTION: Ovarian cancer (OvCa) is the most lethal gynecologic malignancy as women commonly present with metastatic disease that ultimately develops chemotherapy resistance. The development of OvCa has been linked to alterations in DNA repair pathways and the poly (adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitor olaparib has demonstrated antitumor activity and is an FDA approved monotherapy for the treatment of recurrent OvCa in patients with a germline BRCA mutations. Despite promising response rates, not all patients derive benefit, and the majority develop resistance to this therapy that is poorly understood. We hypothesized that ultimate resistance to olaparib is in part mediated by small populations of cancer stem cells (CSCs) that are unaffected by olaparib therapy and may promote tumor resurgence. METHODS: UWB1.289 (BRCA1 mutated), UWB1.289 (WT), OVCAR4 (WT), and OVCAR3 (WT) cell lines and primary cell lines derived from serous OvCa obtained with IRB approval were treated in vitro with 0.1 μM, 1 μM and 10 μM olaparib for 7 days. We assessed cell viability and CSC marker expression (CD133 and CD117) via flow cytometric analysis, and sphere forming capacity via extreme limiting dilution assay (ELDA). RESULTS: Consecutive treatment over 7 days with olaparib decreased the viability of the non–sorted tumor cell population relative to the vehicle control treated cells. Despite the decrease in total cell number, the relative frequency of CD133+ and CD117+ cells increased (all lines p &amp;lt;0.05) in response to treatment with olaparib. This shift was not observed in vehicle treated cells. The increase in CD133+ and CD117+ cell frequency in response to olaparib was not different in the BRCA1 mutant line when compared to the BRCA1 wild type lines. ELDA revealed an increase in the frequency of sphere formation following olaparib treatment relative to that observed with vehicle treated cells, though mutation status did not impact this frequency. CONCLUSIONS: These results suggest that olaparib may enrich for CSC populations that could contribute to resistance and recurrence. These data expose a potential resistance mechanism to olaparib therapy that is in part independent of BRCA mutation status. Citation Format: Chiara Bellio, Rosemary Foster, Whitfield B. Growdon Panagiotis Konstantinopoulos, and Bo R. Rueda. INHIBITION OF POLY ADP–RIBOSE POLYMERASE (PARP) IN OVARIAN CANCER CELLS ENRICHES FOR CD133 AND CD117 POSITIVE POPULATIONS [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr MIP-047.
Disparities in liver cancer occurrence in the United States by race/ethnicity and state
Authors: Farhad Islami, Kimberly D. Miller, Rebecca L. Siegel, Stacey A. Fedewa, Elizabeth M. Ward, Ahmedin Jemal
Journal: CA A Cancer Journal for Clinicians (2017)

Abstract Liver cancer is highly fatal, and death rates in the United States are increasing faster than for any other cancer, having doubled since the mid‐1980s. In 2017, it is estimated that the disease will account for about 41,000 new cancer cases and 29,000 cancer deaths in the United States. In this article, data from the Surveillance, Epidemiology, and End Results (SEER) Program and the National Center for Health Statistics are used to provide an overview of liver cancer incidence, mortality, and survival rates and trends, including data by race/ethnicity and state. The prevalence of major risk factors for liver cancer is also reported based on national survey data from the Centers for Disease Control and Prevention. Despite the improvement in liver cancer survival in recent decades, only 1 in 5 patients survives 5 years after diagnosis. There is substantial disparity in liver cancer death rates by race/ethnicity (from 5.5 per 100,000 in non‐Hispanic whites to 11.9 per 100,000 in American Indians/Alaska Natives) and state (from 3.8 per 100,000 in North Dakota to 9.6 per 100,000 in the District of Columbia) and by race/ethnicity within states. Differences in risk factor prevalence account for much of the observed variation in liver cancer rates. Thus, in contrast to the growing burden, a substantial proportion of liver cancer deaths could be averted, and existing disparities could be dramatically reduced, through the targeted application of existing knowledge in prevention, early detection, and treatment, including improvements in vaccination against hepatitis B virus, screening and treatment for chronic hepatitis C virus infections, maintaining a healthy body weight, access to high‐quality diabetes care, preventing excessive alcohol drinking, and tobacco control, at both the state and national levels. CA Cancer J Clin 2017;67:273–289. © 2017 American Cancer Society.
Moderate drinking is linked to decline in brain health, study finds
Authors: Zosia Kmietowicz
Journal: BMJ (2017)

Alcohol consumption, even at moderate levels, is associated with increased risk of adverse brain outcomes and a steeper decline in cognitive skills, a study published in The BMJ has found.1

The authors said that these results support recent reductions in recommended alcohol limits in the UK to no more than 14 units of alcohol a week for men and women,2 adding that they raise questions about the current US limits.

Heavy drinking is known to be associated with poor brain health, but few studies have examined the effects of moderate drinking on the brain, and results are inconsistent.

To investigate the association between alcohol consumption and the brain’s structure and function, researchers from …
Personalized molecular oncology: An initial case series
Authors: Eric Lester, Craig Webb
Journal: Clinical Cancer Research (2007)

B27  Effective cancer therapies require the understanding of the many driving genetic and epigenetic alterations characteristic of each tumor. A broad examination of gene expression reflects these underlying changes. Here we explored the use of gene expression profiling in the individualized selection of chemotherapy for patients (pts) with advanced incurable cancer. Methods: With informed consent we obtained fresh frozen tumor samples from 7 pts. Gene expression was evaluated using Affymetrix U-133 Plus 2 GeneChips. The XenoBase (XB-BIS) system generated lists of aberrantly expressed genes in each tumor as well as drugs targeting these genes/proteins. Potential targets for available drugs were evaluated in particular (eg.VEGF, EGFR, TOP2A, ERCC1, RRM1, HER2, etc.). These data were shared with the oncologist (EPL) who selected drugs based upon pt informed consent, appropriate standards of care, available clinical data, and gene/drug data. Results: One stage IV non-small cell lung cancer (NSCLCA) pt achieved a near complete response with erlotinib, cisplatin, docetaxel, and bevacizumab (bev) (high EGFR, low ERCC1, high RRM1, and high VEGF). A second NSCLCA pt responded to third-line drugs with etoposide and bev (high TOP2A and VEGF). A recurrent ovarian ca pt had a tumor marker response to gemcitabine and bev (low RRM1, high VEGF) and had stable disease for 4 months on etoposide (high TOP2A) and bev. A renal ca pt showed partial remission after nephrectomy (high VEGF & VEGFR) and is maintained on sunitinib. One heavily pre-treated NSCLCA pt received herceptin (high HER2) and bortezomib with ongoing bev as third-line chemo but withdrew consent for more treatment and died 3 weeks later. A heavily pre-treated plasmacytoma pt responded to empiric bortezomib, thalidomide, and dexamethesone but relapsed and died before gene/drug data could be utilized. A recurrent lymphoma pt is too early to evaluate. Conclusion: A personalized molecular oncology approach, basing chemotherapy on relative gene expression in tumors, holds promise even at the relatively crude level employed here. Future studies correlating clinical/preclinical responses with gene expression data will permit development of more sophisticated algorithms for predicting the activation status of drug targets and biomarkers of drug efficacy, and determining their true value for predicting clinical behavior and tumor response.
Promoting Compliance to Practice Guidelines May Improve Primary Care for Thyroid Diseases—Reply
Authors: Rene Rodriguez-Gutierrez, Paola Portillo-Sanchez, Juan P. Brito
Journal: JAMA Internal Medicine (2017)

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 Internal Medicine 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 Internal Medicine journal
Extracellular matrix (ECM) protein fragments in serum and outcomes in two metastatic breast cancer cohorts.
Authors: Nicholas Willumsen, Kim Leitzel, Suhail M. Ali, Vinod Nagabhairu, Eric Marks, Hyma Vani Polimera, Angelique Ellerbee Richardson, Laura Krecko, Ayesha Ali, Diana Julie Leeming, Morten Asser Karsdal, Allan Lipton
Journal: Journal of Clinical Oncology (2017)

1085 Background: Extracellular matrix (ECM) is the non-cellular component of all tissues. Increased ECM formation and matrix metallo-protease (MMP) mediated ECM degradation are parts of tumorgenesis. The altered ECM remodeling generates specific ECM fragments that are released into the circulation. We evaluated the association of specific ECM/collagen fragments measured in serum with outcomes in two independent metastatic breast cancer (MBC) cohorts. Methods: C1M (MMP-degraded type I collagen), C3M (MMP-degraded type III collagen), C4M (MMP-degraded type IV collagen), and PRO-C3 (pro-peptide reflecting truetype III collagen formation) were measured by ELISA in pre-treatment serum from a phase III randomized clinical trial of 2 nd -line hormone therapy (HR+, n= 153), and a 1 st -line trastuzumab-treated cohort (HER2+, n=64). In both cohorts, all sites of metastases were included. The collagen-fragments were evaluated on continuous and categorical (75 th percentile cut-off) bases by univariate Cox-regression analysis for their association with time-to-progression (TTP) and overall survival (OS). Results: In the HR+ cohort, Pro-C3 measured as a continuous variable was significantly associated with TTP; C1M, C4M and Pro-C3 were associated with OS. On a categorical basis, C1M and C3M were associated with TTP; all fragments were associated with OS (Table). In the HER2+ cohort, continuous measurements of all fragments were associated with TTP and OS. On a categorical basis (Table), all fragments were associated with TTP; C4M and Pro-C3 were associated with OS. Conclusions: ECM remodeling quantified in pre-treatment serum was associated with shorter TTP and OS in two independent MBC cohorts receiving systemic therapy. If validated, quantification of ECM remodeling in serum has potential as prognostic and/or predictive biomarkers in MBC. [Table: see text]
Diagnostic and therapeutic outcomes in goblet cell appendiceal neuroendocrine tumors.
Authors: Christos Toumpanakis, Alex Baneke, Marinos Pericleous, Tim Meyer, Martyn E Caplin
Journal: Journal of Clinical Oncology (2012)

e14696 Background: Goblet cell appendiceal neuroendocrine tumours (GCA-NETs), comprise approximately 6% of appendiceal neuroendocrine tumours (NETs) and share histologic features of both adenocarcinomas and NETs. We are presenting our data from 37 patients, focusing on diagnostic features, prognostic markers, treatment and survival. Methods: A retrospective analysis included 18 male and 19 female patients (mean age: 48.8; range: 19-73 years). Follow-up was complete (mean follow-up: 4.1 years). Results: Although majority of patients (69%) presented with appendicitis, 15.5% had bowel obstruction and 15.5% atypical abdominal pain. 27% had metastases at presentation (1 in lungs). Chromogranin-A, CEA and CA-125 were not significantly raised in these patients. Initial treatment was appendicectomy (26 patients) and 24/26 had a subsequent prophylactic right hemicolectomy. Additional hysterectomy and bilateral oophorectomy was performed in 6 patients and 4 patients just underwent either single or bilateral oophorectomy . 12% had recurrence and all had Ki67 proliferation index ≥ 20%. Octreoscan was negative, but FDG-PET was positive in all these patients, and in patients with distal metastases at presentation. FOLFOX chemotherapy was given prophylactically in 2 patients with local lymph nodes resulting in no evidence of recurrence (Median=8 months) and in 2 patients with distal metastases resulting in only temporary disease stabilization. 19% have died with disease and again all had Ki67 ≥ 20%. Conclusions: GCA-NETs may metastasize to the lungs (first report in literature). Ki67≥ 20% seems to be related with a worse prognosis. FDG-PET is the molecular imaging of choice. No optimal biomarkers or chemotherapy regimens are available to date.
Risk factors associated with brain metastases in ECOG-ACRIN E1505, a phase III randomized trial of adjuvant chemotherapy with or without bevacizumab for patients with completely resected stage IB (&gt;/= 4 cm) - IIIA non-small cell lung cancer (NSCLC).
Authors: John M. Varlotto, Suzanne Eleanor Dahlberg, Heather A. Wakelee, Suresh S. Ramalingam, Joan H. Schiller
Journal: Journal of Clinical Oncology (2017)

8539 Background: ECOG-ACRIN E1505 was a phase III randomized trial of adjuvant chemotherapy with or without bevacizumab for patients with completely-resected Stage IB (&gt;4CM) – IIIA non-small cell lung cancer. Prior studies have shown that the risk of brain recurrence in patients after definitive surgical resection is approximately 10%; however, covariates associated with development of brain recurrence have varied across these studies. We sought to estimate the incidence of and risk factors for brain recurrence. Methods: Among the 1501 patients enrolled to ECOG-ACRIN E1505, 121 patients developed brain metastases as their first site of recurrence and are the subject of this investigation. All 1501 patients underwent a pneumonectomy (N = 192) or (bi)lobectomy and had an R0 resection. The cumulative incidence of brain recurrence was estimated after adjusting for recurrence at other sites and death as competing events. A multivariable regression model was fitted using the methodology of Fine and Gray to evaluate the effect of covariates on the subdistribution of brain recurrence. Results: With a median follow-up of 50.3 months, a total of 121 brain metastases had been reported as the first site of recurrence. The incidence of brain recurrence at 12 months post-randomization was 3.7% (95% CI: 2.8% – 4.7%), and it increased to 8.5% (95% CI: 7.0% - 10.0%) at 3 years, and to 9.9% (95% CI: 8.0% - 11.7%) at 6 years. Risk factors for brain metastases included pneumonectomy(HR=1.8; p=0.01), and nonsquamous histology(HR=2.04; p=0.003), but bevacizumab(HR=0.64; p=0.02) was associated with potentially protective effect. Conclusions: The cumulative incidence of brain recurrence increased over time to 9.9% at 6 years in this population of patients with surgically-resected non-small cell lung cancer. Treatment, tumor histology, and type of resection appear to be associated with the risk of brain recurrence. Clinical trial information: NCT00324805.
PET/MR in the Assessment of Pediatric Histiocytoses
Authors: Andrew C. Sher, Robert Orth, Kenneth McClain, Carl Allen, Shireen Hayatghaibi, Victor Seghers
Journal: Clinical Nuclear Medicine (2017)

The aim of this study was to analyze the feasibility and diagnostic performance of F-FDG PET/MR compared with F-FDG PET/CT in a cohort of pediatric histiocytosis patients with regard to image quality, lesion detection, and FDG quantification.Children with a diagnosis of Langerhans cell histiocytosis or Rosai-Dorfman disease were prospectively recruited. Seventeen PET/CT and PET/MR examinations were performed on 9 patients (mean age, 6.2 years) following a single-injection dual-imaging protocol. The indication was Langerhans cell histiocytosis in 10 examinations and Rosai-Dorfman disease in 7 examinations. The anonymized data were evaluated for image quality and lesion detection. SUV quantification of each lesion was compared between modalities.All PET/MR examinations had good or excellent image quality and were deemed clinically acceptable. There was substantial agreement of PET image quality among readers of PET/MR images. Per patient, PET/MR and PET/CT had complete concordance in identifying active disease. PET/MRI correctly classified 74 (96%) of 77 foci of disease identified on PET/CT. The per-lesion maximum SUVs were strongly correlated between modalities with a Spearman correlation coefficient of 0.73 (P < 0.001).The use of PET/MR is clinically feasible in pediatric patients with a histiocytic disease. PET/MR demonstrates comparable image quality and lesion detection to PET/CT while maintaining strongly correlated quantitative performance. Given the significant radiation dose savings, PET/MR represents an appealing alternative to PET/CT in the care of children with histiocytic disorders.
30-Year Mortality After Venous Thromboembolism
Authors: Kirstine Kobberøe Søgaard, Morten Schmidt, Lars Pedersen, Erzsébet Horváth–Puhó, Henrik Toft Sørensen
Journal: Circulation (2014)

Background— Studies on long-term mortality after venous thromboembolism (VTE) are sparse. Methods and Results— Using Danish medical databases, we conducted a 30-year nationwide population-based cohort study of 128 223 patients with first-time VTE (1980–2011) and a comparison cohort of 640 760 people from the general population (without VTE) randomly matched by sex, year of birth, and calendar period. The mortality risks for patients with deep venous thrombosis (DVT) and pulmonary embolism (PE) were markedly higher than for the comparison cohort during the first year, especially within the first 30 days (3.0% and 31% versus 0.4%). Using Cox regression, we assessed mortality rate ratios (MRRs) with 95% confidence intervals (CIs). The overall 30-year MRR was 1.55 (95% CI, 1.53–1.57) for DVT and 2.77 (95% CI, 2.74–2.81) for PE. The 30-day MRR was 5.38 (95% CI, 5.00–5.80) for DVT and 80.87 (95% CI, 76.02–86.02) for PE. Over time, the 30-day MRR was consistently 5- to 6-fold increased for DVT, whereas it improved for PE from 138 (95% CI, 125–153) in 1980 to 1989 to 36.08 (95% CI, 32.65–39.87) in 2000 to 2011. The 1- to 10-year and 11- to 30-year MRRs remained 25% to 40% increased after both DVT and PE but were 3- to 5-fold increased after DVT and 6- to 11-fold increased after PE when VTE was considered the immediate cause of death. Conclusions— Patients with VTE are at increased risk of dying, especially within the first year after diagnosis, but also during the entire 30 years of follow-up, with VTE as an important cause of death. Although 30-day mortality after DVT remained fairly constant over the last 3 decades, it improved markedly for PE.
French comment on article Reassessment colonoscopy to diagnose serrated polyposis syndrome in a colorectal cancer screening population1 Coloscopie de réévaluation pour le diagnostic de polypose festonnée en situation de dépistage
Journal: Endoscopy (2017)

Les progrès de la qualité optique des endoscopes sont corrélés à une augmentation de détection des polypes festonnés. La polypose festonnée, dont la prévalence est de l’ordre de 0,5 %, est définie: 1/ par la présence d’au moins 5 lésions festonnées en amont du sigmoïde dont au moins 2 de plus de 10 mm de diamètre, 2/ ou par la présence d’au moins une lésion festonnée en amont du sigmoïde en cas d’antécédent de polypose festonnée au premier degré, 3/ ou par la présence de plus de 20 lésions festonnées sur l’ensemble du colon.
Pre-clinical analysis of the CDK4/6 inhibitor palbociclib in HER2-positive breast cancer.
Authors: Bilal ElChaarani, Hillary Stires, Paula Raffin Pohlmann, Rebecca Riggins
Journal: Journal of Clinical Oncology (2017)

e12520 Background: There has been substantial progress in treatment of metastatic HER2+ breast cancer, unfortunately, treatment progression of the disease is universal. Palbociclib is an oral cyclin-dependent kinase (CDK) 4/6 inhibitor that is FDA approved in combination with endocrine therapy for treatment of patients with ER+ metastatic breast cancer. Here we present pre-clinical studies in HER2+ breast cancer cell lines investigating whether addition of palbociclib to the combination of trastuzumab and pertuzumab (TP) is an effective therapy, and whether we could identify predictive biomarkers for palbociclib in this setting. Methods: Crystal violet assays to measure growth of BT-474 (HER2+, ER+), SKBr3 (HER2+, ER-) and MDA-MB-361 (HER2+, ER+ but resistant to TP) were performed in the presence and absence of TP (5 µg/ml each) with increasing concentrations of palbociclib (25-500 µg/ml). Western blots were performed in the presence and absence of TP with and without palbociclib to demonstrate efficacy of TP (blocking phosphorylation of HER2), palbociclib (blocking phosphorylation of Rb), and expression of NIMA-related kinase 2 (NEK2), an established downstream target of CDK4 in HER2+ breast cancer cells. Results: We found growth inhibition in response to palbociclib as single agent in a dose-dependent manner in BT-474, SKBr3, and MDA-MB-361 cells (P &lt; 0.05). Treatment with TP prevented growth in BT-474 and SKBr3 cells to such a great extent that an additive effect between TP and palbociclib was not detectable. However, treatment with palbociclib maintained a dose-dependent decrease in growth in the presence of TP in MDA-MB-361 cells (P &lt; 0.05). Western blots showed decreased expression of pHER2 in response to TP in BT-474 and SKBr3, but not in MDA-MB-361. Treatment with palbociclib decreased pRB in BT474, SKBr3, and MDA-MB-361 with or without TP. NEK2 expression, however, was not affected in any of these cell lines. Conclusions: Palbociclib has an inhibitory effect in resistant and non-resistant HER2-positive cell lines suggesting palbociclib represents an alternate targeting pathway for growth inhibition. Our initial work did not show reliable biomarkers to predict palbociclib effects.