tbuckley/cabot-search huggingface dataset:
Impact of neoadjuvant HER2-directed therapy on HER2 status in breast cancer.
Authors: Nicholas Manguso, Jeffrey Johnson, Reva Kakkar Basho, Heather L. McArthur, Hisashi Tanaka, Armando E. Giuliano
Journal: Journal of Clinical Oncology (2017)

e12130 Background: Neoadjuvant chemotherapy (NAC) with HER2-directed therapy has become standard-of-care for most women with potentially curable HER2-positive (HER2+) breast cancer and is associated with a high pathologic complete response (pCR) rate. The HER2 status of residual disease after NAC is not well characterized and could potentially inform clinical decisions about additional systemic therapy. We describe tumoral HER2 status before and after NAC with HER2-directed therapy. Methods: An institutional database was screened to identify patients with stage 1-3 HER2+ breast cancer by fluorescence in situ hybridization (FISH) and/or immunohistochemistry (IHC) who received NAC with HER2-directed therapy followed by resection between 2011 and 2015. Clinicopathologic data was collected. Change in HER2 status by FISH and IHC following treatment was described. Results: 99 patients were identified. Median age was 49 years (range 26-85). Pre-treatment median HER2/CEP17 copy number ratio (CNR) for all tumors was 6.3 (range 1.9-20.7) by FISH and 84 (84.8%) tumors were IHC 3+. 44 (44.4%) patients achieved a pCR. Of the 55 patients with residual disease, 35 had sufficient residual tumor to evaluate HER2 status and 14/35 (40%) were HER2- by FISH and IHC (table). Tumors converting from HER2+ to HER2- had lower pre-treatment median HER2 copy numbers (11.9, range 4.6-22) compared to tumors that remained HER2+ (18.3, range 5.1-48.6; p=0.04) after neoadjuvant therapy. Additionally, pre-treatment median HER2/CEP17 CNR was lower among tumors that converted from HER2+ to HER2- (3.0, range 2.2-8.2) compared to those remaining HER2+ (6.8, range 2-15.7; p=0.02). Conclusions: While pCR rates are high with NAC and HER2-directed therapy, many patients still have residual tumor. In this cohort, 40% of patients with evaluable residual disease after NAC had HER2+ tumors that became HER2-. HER2 conversion was associated with lower pre-treatment HER2 copy numbers and HER2/CEP17 CNR. Conversion from HER2+ to HER2- in patients undergoing neoadjuvant therapy may have clinical significance and biological implications. [Table: see text]
Cytochrome c Oxidase Activity Is a Metabolic Checkpoint that Regulates Cell Fate Decisions During T Cell Activation and Differentiation
Authors: Tatyana N. Tarasenko, Susan E. Pacheco, Mary Kay Koenig, Julio Gomez-Rodriguez, Senta M. Kapnick, Francisca Diaz, Patricia M. Zerfas, Emanuele Barca, Jessica Sudderth, Ralph J. DeBerardinis, Raul Covian, Robert S. Balaban, Salvatore DiMauro, Peter J. McGuire
Journal: Cell Metabolism (2017)
A library of novel monoclonal antibodies for determining levels of 4-hydroxy cyclophosphamide in biological fluids
Authors: Salvatore J. Salamone, Jodi B. Courtney, Yunying Li, Dennis Stocker, O. Michael Colvin
Journal: Cancer Research (2006)

Proc Amer Assoc Cancer Res, Volume 47, 2006

3107 

The objective of this work was to develop monoclonal antibodies for a stable form of 4-hydroxy cyclophosphamide (HCY) in order to develop a rapid immunoassay for determining levels of HCY in the plasma of patients undergoing cyclophosphamide (CY) treatment. Cyclophosphamide is a widely used chemotherapeutic drug included in a number of cancer regimens. Cyclophosphamide is actually a pro-drug that becomes clinically active following metabolic conversion to HCY. Studies have shown high pharmacokinetic variability of cyclophosphamide and a relationship between systemic levels of the drug and clinical outcome. Determination of HCY levels in patient samples has been difficult because of the instability of this species. Several methods have been developed to trap HCY in a stable form as a hydrazone or an oxime so quantitative analysis by mass spectroscopic methods can be performed. An immunoassay would provide a rapid, automated method to determine levels of HCY in patient samples. However this is complicated since immunogens used to elicit antibody response to HCY would quickly decompose before an immunological response could be achieved. To circumvent this stability issue an immunogen was prepared to a stabilized form of HCY. The O-methyl oxime of HCY was attached to keyhole limpet hemocyanin (KLH) or bovine thyroglobulin (BTG) via a hydrocarbon tether bound through the phosphamide nitrogen. These immunogens were successful in eliciting nine highly selective monoclonal antibod ies for the O-methyl oxime of HCY with dose response curves in the range of 50 ng/mL to 3000 ng/mL by ELISA . The Table below lists performance characteristics that are elicited by this type of immunogen. [Table][1]: Monoclonal antibody 2.7B5-11 performance characteristics This library of monoclonal antibodies is the first report of antibodies able to measure HCY by detecting a stabilized derivative. These antibodies will be useful for the rapid and cost effective analysis of HCY in human samples. By monitoring the active form of the drug it should be possible to better adjust dosing of cyclophosphamide to individual patients.



![Figure][2]  [1]: #F1
 [2]: pending:yes
NEUROMUSCULAR CONTROL ADAPTATIONS TO BALANCE TRAINING: A SYSTEMATIC REVIEW
Authors: Sheila Miho Sato
Journal: British Journal of Sports Medicine (2017)

Background Balance training (BT) programs seem to be appropriate for non-athletes and athletes, but the use of multi-intervention BT protocols make difficult to observe how balance exercises improve neuromuscular control. Objective The purpose of this study is to evaluate the current knowledge regarding the neuromuscular control adaptations in healthy participants following a BT protocol with exclusively balance exercises. Design Systematic review. Setting Randomised controlled trials and controlled clinical trials. Patients (or Participants) Healthy and physically active participants. Interventions (or Assessment of Risk Factors) The methodological quality and risk of bias were assessed using a modified Downs and Black checklist. Main Outcome Measurements The primary outcome is the measurements of electromyography (EMG) activity, like the rate of muscle activation, H-reflex, and M-wave. Results There were inconsistent findings regarding neuromuscular control outcomes. In relation to muscular activity observed by EMG signs, there was no change in the majority of the studies. However, one study reported a decrease in EMG activity for plantar flexors, and two studies observed an increase in muscular activity for soleus, gastrocnemius medialis, and quadriceps muscles after BT. Concerning H-reflex/M-wave ratio of the soleus muscle, two studies observed no change, while three studies reported significant reduction. Also, the reduction observed in the H-reflex/M-wave ratio was associated with a decrease of the maximal H-reflex and no change of the maximal W-wave. Following BT, the rate of force development normalized by maximum voluntary contraction (MVC) had a transient increase for plantar flexors and leg extensors. Although some authors reported a slight enhancement or no improvement on isometric MVC for plantar flexors, leg extensors, quadriceps, and hamstrings muscles. Conclusions Despite the moderate level of proof for neuromuscular control enhancement following BT, adaptations in neuromuscular control remain a significant factor to determine an appropriate exercise that would improve specific athletic performance.
Socially Assistive Robots Help Patients Make Behavioral Changes
Authors: Jennifer Abbasi
Journal: JAMA (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 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
Surgical management associates independently with improved survival among de novo stage IV breast cancer patients without liver or brain metastasis.
Authors: Cuizhi Geng, Wenjin Zhang, Zhensheng Li
Journal: Journal of Clinical Oncology (2017)

e12106 Background: To examine the independent effect of surgical management of the primary tumor and axillary lymph node on survival in patients with de novo Stage IV breast cancer (BC) Methods: 113 patients with de novo stage BC between 2010 to 2013 were followed up to Oct. 1, 2016. Multivariable Cox proportional hazard models were constructed to assess the effect of mastectomy (MAS) and axillary lymph node dissection (ALND) on overall survival (OS) after univariate analyses and K-M curves. Non-treatment covariates included age, BMI, menopause, Stage T, Stage N, ER, PR, HER2, Ki67&gt;14% status, and metastasis sites (lung, liver, bone, brain and others). Chemotherapy, hormonal, target treatement and radiotherapy before the disease progression were others. Results: Mean age 52 (24 - 84) years old, metastasis site by bone 53% (60), lung 32% (36), liver 32% (36), brain 2% (2), and other 23% (23). Median survival 21.4 months. All 42% (48) surgical patients had simultaneous MAS and ALND. Younger (mean 49 vs. 54) and fewer post-menopause (42% vs. 62%) were significantly noticed in surgical patients with median survival 37.8 vs. 14.2 months of others. Multivariable analysis showed OS favorable HRs 0.53 (95% CI 0.24 - 1.17, p=0.12) of surgery and HR 0.48 (0.22 - 1.04, p=0.06) of hormonal drug, and significant HR 0.10, (0.02 - 0.52, p&lt;0.01) of target therapy, insignificant effects of chemotherapy HR 0.60(0.26 - 1.42, p=0.25) and radiotherapy HR 0.70 (0.33 - 1.50, p =0.36). Unfavorable metastasis sites were identified as brain and liver at multivariable model for subgroup analysis. K-M curves estimated median survival 29.3 vs. 14.4 months (favorable vs. unfavorable patients). Both univariate and multivariate analyses showed the significant effect of surgery in favorable subgroup (N=76) with HR 0.30 (0.16 - 0.56, p &lt;0.01) and 0.33 (0.11 - 0.98, p=0.05) on OS, respectively. In unfavorable subgroup (N=37), the results were insignificant effect of surgery on OS with HR 0.75 (0.37 - 1.55, p=0.54) and 1.60 (0.33 - 7.81, p=0.56). Conclusions: Surgical management associated independently with improved survival among de novo stage IV BC patients without liver or brain metastasis.
Quality of Life Scores Improve with Increasing Hemoglobin but Optimal Thresholds Vary According to Transfusion Dependence and Clinical Risk Scores: A Canadian Cross Sectional Study of 689 Patients with 2969 Measurements
Authors: Rena Buckstein, Richard A. Wells, Nancy Y Zhu, Michelle Geddes, Mitchell Sabloff, Brian Leber, Mary-Margaret Keating, John MH Storring, Karen W.L. Yee, Heather Leitch, Eve St-Hilaire, Thomas J. Nevill, April Shamy, Rajat Kumar, Mohamed Elemary, Robert Delage, Martha Lenis, Alexandre Mamedov, Jessica Ivo, Shabbir MH Alibhai
Journal: Blood (2016)
Increased Risk of Death, in the Hospital and Outside the Intensive Care Unit, for Patients With Cirrhosis After Cardiac Arrest
Authors: Megan E. Reinders, Gabriel Wardi, Ricki Bettencourt, Daniel Bouland, Jessica Bazick, Michel Mendler, Irine Vodkin, Denise Kalmaz, Thomas Savides, David Brenner, Rebecca E. Sell, Rohit Loomba
Journal: Clinical Gastroenterology and Hepatology (2017)
Epstein-Barr Virus–Positive Mucocutaneous Ulcer Mimicking Rectal Carcinoma at 18F-FDG PET/CT
Authors: Anna Margherita Maffione, Lucia Rampin, Rossella Paolini, Elisabetta Rodella, Laura Camilla Lisato, Maria Rosa Ballotta, Giovanni Pavanato, Giampaolo Montesi, Patrick M. Colletti, Domenico Rubello
Journal: Clinical Nuclear Medicine (2017)

We report focally intense F-FDG PET/CT rectal activity (SUVmax = 25) with a horseshoe distribution in an 81-year-old man with B-cell chronic lymphocytic leukemia and suspected Richter transformation. While imaging findings were typical for rectal adenocarcinoma, histology revealed Epstein-Barr virus-positive mucocutaneous ulcer.
Abstract MIP-072: IDENTIFICATION OF THE SIGNALING PATHWAYS DOWNSTREAM OF PTEN LOSS IN FALLOPIAN TUBE LEADING TO INITIATION AND PROGRESSION OF HGSOC
Authors: Angela Russo, Joanna E. Burdette
Journal: Clinical Cancer Research (2017)

Abstract High-grade serous ovarian carcinoma (HGSOC) is the most common histotype of ovarian cancer with the highest mortality rate. The lethality of these tumors is due mainly to the difficulty in detecting the disease at early stages. The findings of early lesions in the fallopian tube suggest that HGSOC may originate from the fallopian tube epithelium (FTE) and metastasize to the ovary. Recent transgenic animal models of FTE-derived HGSOC have pointed out the critical role of loss of PTEN (phosphatase and tensin homolog) in generating HGSOC when in combination with p53 mutation and alteration of BRCA1/2, but not by itself. Our lab was the first to show that deletion of PTEN alone in FTE is sufficient to lead to tumor formation and peritoneal dissemination suggesting that the importance of PTEN in the early events of the tumorigenic cascade may have been underestimated. Indeed, it has been found that loss of PTEN is a common alteration in STIC lesions. Recent studies revealed that loss of PTEN is predicted to be much more common (30% more) in HGSOC when the DNA contribution from stroma is excluded from tumor DNA analysis. The understanding of the sequence of the molecular alterations behind the genesis of HGSOC from FTE remains poorly defined and pivotal to early detection of HGSOC. The purpose of this study was to identify the markers of cancer initiation and progression altered upon loss of PTEN in FTE. Our data revealed increased mRNA levels of signaling components of the non-canonical (βcatenin-independent) WNT pathway. βcatenin was indeed not activated upon loss of PTEN, however inhibition of the WNT canonical and non-canonical pathway blocked PTEN-induced migration and ovarian colonization suggesting that the WNT non-canonical pathway is mediating loss of PTEN-induced tumorigenesis. Citation Format: Angela Russo, Joanna E. Burdette. IDENTIFICATION OF THE SIGNALING PATHWAYS DOWNSTREAM OF PTEN LOSS IN FALLOPIAN TUBE LEADING TO INITIATION AND PROGRESSION OF HGSOC [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-072.
Image Gallery: Microcystic adnexal carcinoma (syringomatous carcinoma and sclerosing sweat duct carcinoma) as an extensive sclerotic erythematous plaque with telangiectasia over the face
Authors: T. Namiki, K. Nojima, S. Tokoro, T. Hanafusa, H. Yokozeki
Journal: British Journal of Dermatology (2017)

Funding sources: none. Conflicts of interest: none declared. Dear Editor, A 79‐year‐old woman presented with a sclerotic erythematous plaque on her cheeks, forehead and nose (a, b). Telangiectasia was noted on her left cheek and nose. Histopathology showed tumour nests scattered throughout the entire dermis that had infiltrated into the cutaneous fat and partially into the muscle layers (c). Most of the tumour nests manifested tubular structures, and some had a silhouette similar to a tadpole appearance (d). Immunohistochemistry showed a positive reaction for epithelial membrane antigen (e). The diagnosis of microcystic adnexal carcinoma was made. It is important to know the various clinical presentations of microcystic adnexal carcinoma, including the features of this case.1,2
Glucose self monitoring may not improve control in non-insulin treated type 2 diabetes
Authors: Susan Mayor
Journal: BMJ (2017)

Patients with type 2 diabetes not treated with insulin who self monitor their blood glucose showed no significant difference in glycaemic control at one year from patients who do not regularly test their own blood glucose levels, a randomised trial has shown.1

Many patients with type 2 diabetes monitor their blood glucose regularly, but previous studies have shown conflicting results on glycaemic control.

Researchers randomly assigned …
Association of CMB305 or LV305-induced and baseline anti-NY-ESO-1 immunity with survival in recurrent cancer patients.
Authors: Seth Pollack, Hailing Lu, Neeta Somaiah, Sant P. Chawla, John Charles Morris, Khanh Tu Do, Joseph W. Kim, Matthew Stephen Block, Marissa Vignali, Julie Rytlewski, Erik Yusko, Frank J. Hsu, Gerry C. Bohac, Sacha Gnjatic, Jan Ter Meulen
Journal: Journal of Clinical Oncology (2017)

3090 Background: The correlation of immune response (IR) and clinical benefit in patients (pts) who receive active immunotherapy remains controversial. CMB305 is an active immunotherapy designed to generate and expand anti-NY-ESO-1 T cells, consisting of LV305 (a DC targeting lentiviral vector encoding NY-ESO-1) and a boost (NY-ESO-1 recombinant protein plus GLA-SE, a TLR-4 agonist). Phase 1 studies of LV305 and CMB305 evaluated the IR and survival of pts with NY-ESO-1 positive tumors. Methods: 62 pts with recurrent NY-ESO-1 expressing (by IHC) solid tumors were enrolled in 2 Phase 1 trials (31 pts each: 43 sarcomas, 12 ovarian, 4 melanomas, and 3 NSCLC). Peripheral blood was assessed pre and post therapy for anti-NY-ESO-1 T cell responses (IFNγ ELISPOT) and antibodies (Ab) (ELISA) (n = 62), TCR-β CDR3 repertoire and conserved (public) TCR (n = 28), and antigen spreading (ELISA, ELISPOT) (n = 23). Relationship between progression-free survival (PFS), overall survival (OS) and up to 15 biomarkers were analyzed by the Kaplan-Meier method. Results: Preexisting anti-NY-ESO-1 T cells and Ab were identified in 34% and 40% of pts. LV305 and CMB305 induced (de novo or increased) anti-NY-ESO-1 T-cells in 51% and 65% pts, and anti-NY-ESO-1 Ab responses in 13% and 68% pts, respectively. LV305 and CMB305 induced antigen spreading in 17% and 36% pts. TCR clonality increased after CMB305 as compared to LV305. The TCRβ-CDR3 amino acid sequences of three NY-ESO-1 specific TCR clones in a patient with a &gt; 2-year response were fully conserved in 20/28 patients. Biomarkers showing the strongest association with OS and PFS were pre-existing anti-NY-ESO-1 T-cell response and Ab, integrated IR (T cells and antibodies), and NY-ESO-1 expression level. Presence of public TCRs was associated with longer survival, particularly in pts with high ( &gt; 50%) NY-ESO-1 expression. Conclusions: While LV305 and CMB305 are both immunogenic, CMB305 resulted in a stronger and broader integrated IR, including antigen spreading. The three identified survival variables, preexisting and treatment-induced NY-ESO-1 IR and the presence of public TCRs, warrant validation in randomized studies of CMB305.
What is the best treatment to reduce the need for caesarean section in nulliparous women at term with delayed first stage of labour?
Authors: Sara Kenyon, Julia Sanders, Lee Middleton, Tracey Johnston
Journal: BMJ (2017)

#### What you need to know

Labour is commonly divided into three stages. The duration of the first and second stages of labour vary, dependent on parity. Figure 1⇓ depicts the stages of labour and expected duration as defined by the National Institute for Health and Care Excellence (NICE).1 Nulliparous women tend to have a longer labour than multiparous women. Delay can result from poor uterine contractions or the relationship between size, presentation, and position of the fetus and the maternal pelvis that obstructs vaginal delivery. Uterine contractile dysfunction affects between 11% and 30% of nulliparous women234 and is the focus of this paper.



Fig 1  The three stages of labour and their expected duration1



Delayed labour— There is some variation worldwide in the definition of delayed labour (table 1⇓). The World Health Organization considers delay as a rate of cervical dilation of less than 0.5-1 cm in four hours once labour is established, whereas NICE recommends waiting a further two hours with cervical dilation of less than 1 cm before delay is confirmed. Prolonged labour is associated with higher rates of chorioamnionitis9 with risk of neonatal sepsis and of unplanned caesarean section with associated risks of infection and bleeding.101112

View this table:

Table 1 
Summary of professional guidelines for normal duration of labour, definition of delay in the first stage of labour, and recommended treatment with oxytocin in nulliparous women



Oxytocin— Treatment for a confirmed delay …
Ectopic calcification in pseudoxanthoma elasticum responds to inhibition of tissue-nonspecific alkaline phosphatase
Authors: Shira G. Ziegler, Carlos R. Ferreira, Elena Gallo MacFarlane, Ryan C. Riddle, Ryan E. Tomlinson, Emily Y. Chew, Ludovic Martin, Chen-Ting Ma, Eduard Sergienko, Anthony B. Pinkerton, José Luis Millán, William A. Gahl, Harry C. Dietz
Journal: Science Translational Medicine (2017)

Ectopic calcification in PXE integrates both local and systemic perturbations of extracellular ATP metabolism and can be attenuated with a TNAP inhibitor.