tbuckley/cabot-search huggingface dataset:
Beta blockers and improved progression-free survival in patients with advanced HER2 negative breast cancer: a retrospective analysis of the ROSE/TRIO-012 study
Authors: G. Spera, R. Fresco, H. Fung, J.R.B. Dyck, E. Pituskin, I. Paterson, J.R. Mackey
Journal: Annals of Oncology (2017)
Lymphocyte density determined by computational pathology validated as a predictor of response to neoadjuvant chemotherapy in breast cancer: secondary analysis of the ARTemis trial
Authors: H.R. Ali, A. Dariush, J. Thomas, E. Provenzano, J. Dunn, L. Hiller, A.-L. Vallier, J. Abraham, T. Piper, J.M.S. Bartlett, D.A. Cameron, L. Hayward, J.D. Brenton, P.D.P. Pharoah, M.J. Irwin, N.A. Walton, H.M. Earl, C. Caldas
Journal: Annals of Oncology (2017)

We have previously shown lymphocyte density, measured using computational pathology, is associated with pathological complete response (pCR) in breast cancer. The clinical validity of this finding in independent studies, among patients receiving different chemotherapy, is unknown.
Minimally Invasive Techniques for Treating Gynecologic Malignancies
Authors: Amanda N. Fader
Journal: Journal of the National Comprehensive Cancer Network (2017)

For many women with endometrial and cervical cancers, minimally invasive surgery represents an alternative standard of care to open abdominal procedures, with fewer complications, better postoperative quality of life, and overall lower cost. At the NCCN 22nd Annual Conference, Amanda N. Fader, MD, reviewed several minimally invasive strategies for treating gynecologic cancers, including conventional laparoscopy, robotic-assisted laparoscopy, sentinel lymph node technology, and single-port surgery; highlighted some of the contemporary literature on the role of these procedures; and explored some of the challenges and barriers to their successful performance.
Proapoptotic signaling induced by deletion of receptor‐interacting kinase 1 and TNF receptor‐associated factor 2 results in liver carcinogenesis
Authors: Petra Hirsova, Maria Eugenia Guicciardi, Gregory J. Gores
Journal: Hepatology (2017)

Hirsova, Petra Ph.D.; Guicciardi, Maria Eugenia Ph.D.; Gores, Gregory J. M.D. Author Information
Exercise training in Diastolic Heart Failure (Ex‐<scp>DHF</scp>): rationale and design of a multicentre, prospective, randomized, controlled, parallel group trial
Authors: Frank Edelmann, Anna Bobenko, Götz Gelbrich, Gerd Hasenfuss, Christoph Herrmann‐Lingen, André Duvinage, Silja Schwarz, Meinhard Mende, Christiane Prettin, Tobias Trippel, Ruhdja Lindhorst, Daniel Morris, Elisabeth Pieske‐Kraigher, Kathleen Nolte, Hans‐Dirk Düngen, Rolf Wachter, Martin Halle, Burkert Pieske
Journal: European Journal of Heart Failure (2017)
Phase II trial of vandetanib in Von Hippel-Lindau-associated renal cell carcinoma.
Authors: Lambros Stamatakis, Brian Shuch, Eric A. Singer, Jeffrey Nix, Hong Truong, Julia C. Friend, Sarah Fowler, Gennady Bratslavsky, Adam R. Metwalli, Joanna H. Shih, W. Marston Linehan, Ramaprasad Srinivasan
Journal: Journal of Clinical Oncology (2013)

4584 Background: Germline mutations in the von Hippel Lindau (VHL) gene are associated with the development of bilateral multifocal clear-cell renal cell carcinoma (RCC). VHL patients with localized disease are surgically managed, with nephron sparing resection recommended once tumors reach 3 cm. Patients typically undergo multiple surgeries with significant cumulative morbidity. In this phase 2 trial of vandetanib, a dual VEGFR2/EGFR inhibitor, a systemic approach to these tumors was explored. Methods: Patients with VHL-associated RCC were treated with 300 mg vandetanib daily until disease progression or unacceptable toxicity. Cross sectional imaging was performed at baseline and every 12 weeks. The primary endpoint was overall renal tumor response assessed by RECIST. Results: A total of 34 subjects were enrolled, with a mean age of 47 years (range 28 – 72). The median number of targeted lesions per subject was 2 (range 1 – 6) and the mean tumor diameter was 2.3 cm (range 1.2 – 4.0). Twenty-seven (80%) subjects had baseline imaging and at least one follow-up study to allow response evaluation. Median time on study was 6.1 months (range 1.0 – 23.3). Thirteen (38%) subjects demonstrated overall reduction in tumor burden with a median reduction of 6% (range 4-54%). One (3%) subject had a PR by RECIST and 26 (77%) had stable disease as their best response. Eleven (32%) subjects were taken off study due to growth of at least one lesion that met criteria for surgical resection or disease progression. Nine (27%) subjects required dose reductions due to toxicity. Although the majority of adverse events encountered on trial were grade 2 or less, 9 (27%) subjects were taken off trial due to drug-related toxicities and 9 (27%) withdrew due to intolerable side effects. Rash (71%), and QTc prolongation (41%) were the most common adverse events noted. Conclusions: In the largest phase II study of a systemic agent for VHL-related RCC, vandetanib demonstrated anti-tumor activity. Despite a reasonable safety profile, poor tolerability necessitated drug withdrawal in a significant proportion of patients. Newer agents that selectively target the VEGF receptors may offer a more tolerable alternative and might optimize clinical benefits in this population. Clinical trial information: NCT0056695.
Unusual Tumors Involving the Head and Neck Region
Authors: Marwan G. Fakih, Marie C. Defrances, N. Paul Ohori, Ramesh K. Ramanathan
Journal: Journal of Clinical Oncology (2001)

Article Tools DIAGNOSIS IN ONCOLOGY Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.21.4173 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11689586 Unusual Tumors Involving the Head and Neck Region Case 1. Angiosarcoma of the Scalp Marwan G. FakihxMarwan G. FakihSearch for articles by this author , Marie C. DefrancesxMarie C. DefrancesSearch for articles by this author , N. Paul OhorixN. Paul OhoriSearch for articles by this author , Ramesh K. RamanathanxRamesh K. RamanathanSearch for articles by this author Show More University of Pittsburgh, Pittsburgh, PA https://doi.org/10.1200/JCO.2001.19.21.4173 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
Designing a survivorship program for head and neck cancer patients.
Authors: Jolie Ringash, Maurene McQuestion
Journal: Journal of Clinical Oncology (2013)

e17007 Background: Our institution receives approximately 700 new patients with head and neck cancer (HNC) annually. A need was identified to develop, provide and evaluate services for the unique needs of HNC patients and their families. Methods: A dual leadership model was established, involving two HNC specialists: an advanced practice nurse and a radiation oncologist. After a literature search and environmental survey, we contacted identified H&amp;N survivorship programs. Internal participants were identified from the HNC clinical team and existing institutional survivorship program. We established interdisciplinary Steering (focused on development and oversight of clinical &amp; education programs) and Research (tasked with assessing needs and outcomes) committees. We sought consensus on program principles, scope, a definition of survivorship, and a theoretical model of the HNC journey. A half-day retreat including community partners and patient/family representatives was held to set 5-year priorities. Results: Little published literature on survivorship initiatives specific to HNC exists. Three HNC survivorship clinical or research programs were identified; the largest (established in 2009) was visited, while telephone contact was made with investigators at the others. Principles guiding program development included interdisciplinary collaboration, grass-roots expertise, and a holistic scope. We defined survivors as all HNC patients and their families, from diagnosis through death. Program scope includes physical, emotional, social, financial, functional and psychosocial needs. A theoretical map of the cancer journey and evolving challenges was developed. The retreat included 50 participants, representing 20 different roles. We identified these top priorities: 1) Establish a post-treatment team; 2) Make survivorship a (mandatory) standard of care; 3) Optimize patient navigation; 4) Match services to specific patient groups (eg. men); 5) Expand access to allied health services; and 6) Develop a clinical care pathway. Conclusions: Survivorship is a complex and evolving area of research and care delivery. A team-based, comprehensive approach has been developed to address the needs of the highly specialized HNC population.
Pragmatic prospection emphasizes utility of predicting rather than mere predictability
Authors: Roy F. Baumeister, Cory J. Clark, JongHan Kim
Journal: Behavioral and Brain Sciences (2017)

Abstract Contrary to one assumption of CLASH, we suggest that colder rather than warm climates are the harsh, unpredictable ones, thus requiring greater self-control. We propose shifting emphasis from predictability to utility of prediction. Northern climates may be less predictable than tropical ones, making predictions and planning far more important, insofar as they can prevent fatalities and promote other pragmatic benefits.
NEMO, a Transcriptional Target of Estrogen and Progesterone, Is Linked to Tumor Suppressor PML in Breast Cancer
Authors: Hanan S. Elsarraj, Kelli E. Valdez, Yan Hong, Sandra L. Grimm, Lawrence R. Ricci, Fang Fan, Ossama Tawfik, Lisa May, Therese Cusick, Marc Inciardi, Mark Redick, Jason Gatewood, Onalisa Winblad, Susan Hilsenbeck, Dean P. Edwards, Christy R. Hagan, Andrew K. Godwin, Carol Fabian, Fariba Behbod
Journal: Cancer Research (2017)

The beneficial versus detrimental roles of estrogen plus progesterone (E+P) in breast cancer remains controversial. Here we report a beneficial mechanism of E+P treatment in breast cancer cells driven by transcriptional upregulation of the NFκB modulator NEMO, which in turn promotes expression of the tumor suppressor protein promyelocytic leukemia (PML). E+P treatment of patient-derived epithelial cells derived from ductal carcinoma
Strategies for Management of Relapsed or Refractory Hodgkin Lymphoma
Authors: Leo I. Gordon
Journal: Journal of the National Comprehensive Cancer Network (2017)

The advent of effective therapies has improved outcomes for those with newly diagnosed Hodgkin lymphoma (HL), with a resulting cure rate of at least 80%. However, with limited data on therapeutic options in the setting of advanced disease, individualized treatment is recommended, and potential long-term effects of therapy remain a key consideration. At the NCCN 22nd Annual Conference, Dr. Leo I. Gordon explored strategies for systemic therapy in the relapsed or refractory setting, focusing primarily on the standard of high-dose therapy/autologous stem cell rescue, the CD30-targeted antibody drug conjugate brentuximab vedotin, and checkpoint inhibition.
Association between duration of treatment (DOT) and healthcare costs in multiple myeloma (MM) patients receiving initial therapy with bortezomib.
Authors: Yongling Xiao, Bruce J. Wong, Patrick Lefebvre, Jonathan Fortier, Esprit Ma, Vijayveer Bonthapally, Mei Sheng Duh
Journal: Journal of Clinical Oncology (2015)

e17792 Background: Extended bortezomib treatment to higher cumulative doses has been shown to be associated with efficacious outcomes, yet there is a lack of real-world evaluation of the association between first-line bortezomib DOT and healthcare costs in MM patients. Methods: A retrospective analysis of US-based Truven Health Analytics MarketScan database from 04/2008 through12/2013 was conducted. MM patients aged ≥ 18 years, initiating first-line bortezomib therapy (index date) with ≥ 6 months’ follow-up were analyzed. Mean healthcare costs per-patient-per-month (PPPM) from the index date to end of insurance eligibility were compared between bortezomib DOT groups ( < 6 months [shorter] or ≥ 6 [longer]). Adjusted mean PPPM cost difference for each cost category was estimated using multivariate linear regression models adjusting for age, sex, Charlson comorbidity index, diabetes, peripheral neuropathy, renal disease, cerebrovascular disease, fractures, year of index-date, region, payer type, baseline medical costs, and baseline pharmacy costs. Non-parametric bootstrap procedures with 999 replications were used to estimate 95% CIs and p-values. Subgroup analyses compared patients with longer initial bortezomib DOT with those who switched to a later line of therapy within the 6 months (switchers). Results: Among 3729 eligible MM patients, 1053 had longer and 2676 shorter bortezomib DOT. Patients with shorter DOT were younger (median 62 vs 65 years). Patients with longer first-line bortezomib DOT had significantly higher PPPM pharmacy costs compared with shorter DOT (adjusted cost difference [CD]: $358, p = 0.006). The higher pharmacy cost associated with longer DOT was offset by lower PPPM medical costs (adjusted CD: –$730, p = 0.016), particularly in inpatient services (adjusted CD: –$1920, p < 0.001). MM patients with longer initial bortezomib DOT also had significantly lower total PPPM healthcare costs than switchers (adjusted CD: –$2782, p < 0.001). Conclusions: MM patients with longer first-line bortezomib DOT had consistently lower healthcare costs. This association was more pronounced when compared with patients who switched therapy.
Positive Selection of Thymocytes
Authors: Stephen C. Jameson, Kristin A. Hogquist, Michael J. Bevan
Journal: Annual Review of Immunology (1995)

Differentiation of αβ T cell receptor (TCR)-expressing T cells involves an obligatory interaction with self-major histocompatibility complex (MHC) molecules in the thymus. This process, called positive selection, both rescues thymocytes from programmed cell death and induces their differentiation into mature T cells. Another critical event in thymic development is to prevent maturation of hazardous autoreactive T cells; thus, mechanisms exist to eliminate T cells with self-reactive receptors (negative selection). How can these two pathways be distinguished? This question, which has long taxed immunologists, is more opposite because many features of the interactions in positive and negative selection are shared: Both processes are exquisitely MHC-allele specific, they involve MHC-bound peptide recognition, and employ at least some overlapping signal transduction pathways. However, resolution of this paradox has become much more feasible with the advent of powerful systems for withdrawing and reconstituting individual components involved in positive selection. This review describes recent advances in our understanding of the cells, receptors, ligands, and signaling pathways involved in this process. A pivotal part of this puzzle is the basis for discrimination between TCR ligands that induce positive vs negative selection. Recent work suggests that the peptide/MHC ligand for positive selection may bind with low avidity to the TCR. The implications of these data for the nature of T cell recognition during positive selection are discussed below.
Prospective analysis of UGT1A1 genotyping for predicting toxicities in advanced colorectal cancer (aCRC) treated with irinotecan (IRI)-based regimens: Interim safety analysis of a Japanese observational study.
Authors: Wataru Ichikawa, Keisuke Uehara, Keisuke Minamimura, Chihiro Tanaka, Yasumasa Takii, Sotaro Sadahiro, Hideaki Miyauchi, Katsunori Shinozaki, Takuya Miyagaki, Toshio Otsuji, Takeshi Kambara, Satoshi Morita, Yuichi Ando, Yukihiro Okutani, Masahiro Sugihara, Toru Sugiyama, Yasuo Ohashi, Yuh Sakata
Journal: Journal of Clinical Oncology (2013)

3535 Background: UGT1A1*6 and UGT1A1*28 are risk factors for severe IRI-related toxicities in Asians, but recommended IRI doses based on UGT1A1 genotypes and other risk factors are unclear. We conducted a prospective analysis to examine the correlation between UGT1A1 genotypes and the efficacy and safety of IRI-based regimens in Japanese aCRC patients (pts), (NCT 01039506). Methods: Pts who had histologically confirmed aCRC, PS of 0–2, received IRI-based regimens (FOLFIRI, IRI+S-1, IRI monotherapy), were UGT1A1 genotyped, and provided written informed consent were included. UGT1A1 polymorphisms were analyzed and categorized into 3 groups: wild (*1/*1), hetero (*1/*6, *1/*28), and homo (*6/*6, *6/*28, *28/*28). Detailed toxicities in the first 3 months of treatment were prospectively recorded. For interim safety analysis, incidences of grade 3–4 (severe) toxicities were compared among UGT1A1 genotypes and a logistic regression model was used to predict the risk of severe toxicities. Severe toxicities and associated risk factors were predicted using a nomogram and bootstrap validation was performed. Results: We enrolled 1376 pts between October 2009 and March 2012. At the time of abstract submission, toxicity data of 504 pts were available; 46% pts had wild, 44% hetero, and 11% homo polymorphisms. FOLFIRI was administered to 63% pts. Severe neutropenia developed during the first 3 months of treatment in 33% pts: 36% in hetero [OR, 1.5; 95% CI, 1.0–2.3], 47% in homo (OR, 2.3; 95% CI, 1.2–4.4), and 28% in wild. Severe diarrhea incidence was 5%, which did not correlate with UGT1A1 genotypes. Multiple logistic regression model included regimen, initial IRI dose, gender, age, UGT1A1 genotype, and PS as predictors of severe neutropenia in the first treatment cycle. The resulting nomogram demonstrated good accuracy in predicting severe neutropenia, with a bootstrap-corrected concordance index of 0.74. Conclusions: Considering UGT1A1 genotype along with other clinical factors is important for managing pts undergoing IRI-based regimens. Our presentation will provide analysis of data from more than 1000 pts. Clinical trial information: NCT01039506.
Obesity is not just elevated adiposity, it is also a state of metabolic perturbation
Authors: Jonathan CK Wells
Journal: Behavioral and Brain Sciences (2017)

Nettle et al. miss the crucial difference between adaptive models of storing energy and explanations for the pathological metabolic state of obesity. I suggest that the association of food insecurity with obesity in women from industrialized settings is most likely due to reverse causation: Poverty reduces agency to resist obesogenic foods, and this scenario is compounded by perturbations of insulin metabolism stemming from high adiposity and lipogenic diets.
Assessment of Breast Cancer Risk Factors Reveals Subtype Heterogeneity
Authors: Johanna Holm, Louise Eriksson, Alexander Ploner, Mikael Eriksson, Mattias Rantalainen, Jingmei Li, Per Hall, Kamila Czene
Journal: Cancer Research (2017)

Abstract Subtype heterogeneity for breast cancer risk factors has been suspected, potentially reflecting etiologic differences and implicating risk prediction. However, reports are conflicting regarding the presence of heterogeneity for many exposures. To examine subtype heterogeneity across known breast cancer risk factors, we conducted a case–control analysis of 2,632 breast cancers and 15,945 controls in Sweden. Molecular subtype was predicted from pathology record–derived IHC markers by a classifier trained on PAM50 subtyping. Multinomial logistic regression estimated separate ORs for each subtype by the exposures parity, age at first birth, breastfeeding, menarche, hormone replacement therapy use, somatotype at age 18, benign breast disease, mammographic density, polygenic risk score, family history of breast cancer, and BRCA mutations. We found clear subtype heterogeneity for genetic factors and breastfeeding. Polygenic risk score was associated with all subtypes except for the basal-like (Pheterogeneity &amp;lt; 0.0001). “Never breastfeeding” was associated with increased risk of basal-like subtype [OR 4.17; 95% confidence interval (CI) 1.89–9.21] compared with both nulliparity (reference) and breastfeeding. Breastfeeding was not associated with risk of HER2-overexpressing type, but protective for all other subtypes. The observed heterogeneity in risk of distinct breast cancer subtypes for germline variants supports heterogeneity in etiology and has implications for their use in risk prediction. The association between basal-like subtype and breastfeeding merits more research into potential causal mechanisms and confounders. Cancer Res; 77(13); 3708–17. ©2017 AACR.
Topical delivery of acetazolamide by encapsulating in mucoadhesive nanoparticles
Authors: Satish Manchanda, Pravat Kumar Sahoo
Journal: Asian Journal of Pharmaceutical Sciences (2017)

The intent of this study was to provide topical delivery of acetazolamide by preparing chitosan-STPP (sodium tripolyphosphate) nanoparticles of acetazolamide and evaluate the particle size, zeta potential, drug entrapment, particle morphology; in vitro drug release and in vivo efficacy. The particles showed sustained in vitro drug release which followed the Higuchi kinetic model. The results indicate that the nanoparticles released the drug by a combination of dissolution and diffusion. The optimised formulation was having particle size 188.46 ± 8.53 nm and zeta potential + 36.86 ± 0.70 mV. The particles were spherical with a polydispersity index of 0.22 ± 0.00. Powder X-ray diffraction and differential scanning calorimetry indicated diminished crystallinity of drug in the nanoparticle formulation. In the in vitro permeation study, the nanoparticle formulation showed elevated permeation as compared to that of drug solution with negative signs of corneal damage. In vitro mucoadhesion studies showed 90.34 ± 1.12% mucoadhesion. The in vivo studies involving ocular hypotensive activity in rabbits revealed significantly higher hypotensive activity (P < 0.05) as compared with plain drug solution with no signs of ocular irritation. The stability studies revealed that formulation was quite stable.
Patient education and access of ESRD patients to renal replacement therapies beyond in-center hemodialysis
Authors: Brad H Rovin, Yuxiao Tang, Junfeng Sun, Haikady N Nagaraja, Kevin V Hackshaw, Linda Gray, Robert Rice, Daniel J Birmingham, Chack-Yung Yu, Dan N Spetie, Amy Aziz, Lee A Hebert
Journal: Kidney International (2005)
Rapid Prenatal Diagnosis of Sickle Cell Anemia by a New Method of DNA Analysis
Authors: Stephen H. Embury, Stephen J. Scharf, Randall K. Saiki, Mary Ann Gholson, Mitchell Golbus, Norman Arnheim, Henry A. Erlich
Journal: New England Journal of Medicine (1987)

We have used a new method of DNA analysis for the rapid prenatal diagnosis of sickle cell anemia in two fetuses at risk for this disease. This method of detecting the sickle gene is a modification of standard restriction-enzyme techniques and requires only a small amount of DNA. The first step involves a 200,000-fold enzymatic amplification of the specific beta-globin DNA sequences that may carry the sickle mutation. This provides a sufficient quantity of DNA for the analysis. Next, a short radiolabeled synthetic DNA sequence homologous to normal beta A-globin gene sequences is hybridized to the amplified target sequences. The hybrid "duplexes" are then digested sequentially with two restriction endonucleases. The presence of beta A- or beta S-globin gene sequences in the amplified target DNA from the patient determines whether the beta A-hybridization probe anneals perfectly or with a single nucleotide mismatch. This difference affects the restriction-enzyme digestion of the DNA and the size of the resulting radiolabeled digestion products, which can be distinguished by electrophoresis followed by autoradiography. This method is sufficiently sensitive and rapid that the prenatal diagnosis of sickle cell anemia can be made on the same day that the fetal DNA is made available. It can also be applied to the diagnosis of hemoglobin C disease.