tbuckley/cabot-search huggingface dataset:
Single CTC characterization to identify phenotypic and genomic heterogeneity as a mechanism of resistance to AR signaling directed therapies (AR Tx) in mCRPC patients.
Authors: Howard I. Scher, Ryon Graf, Jessica Louw, Adam Jendrisak, Ann Johnson, Stephanie Greene, Angel Rodriguez, Nicole A. Schreiber, Brigit McLaughlin, Lyndsey Dugan, Martin Fleisher, Jerry Lee, Yipeng Wang, Dena C. Marrinucci, Mark Landers, Ryan Vance Dittamore
Journal: Journal of Clinical Oncology (2016)

163 Background: AR directed Tx, including Abiraterone (A) and Enzalutamide (E), prolong survival in patients with mCRPC and are FDA approved. After primary Tx with either A or E, the response to E or A is decreased as is the duration of response. NGS tissue sequencing of mCRPC shows a range of disease phenotypes and genotypes which are associated with increased tumor heterogeneity. Single site biopsy, may not represent the diversity of disease. Our objective is to develop biomarkers of heterogeneity from the analysis of single cells from patients with mCRPC. Methods: 221 blood samples from 179 unique patients (pts) were collected from pts about to begin AR Tx (n = 150) or Taxanes (n = 71). Samples were analyzed with the Epic Sciences platform. Analysis included digital pathology of 20 discrete phenotypic cell features inclusive of AR, CK, size and shape measures. 9225 single CTCs were characterized, data standardized, features clustered and categorized into 15 phenotypically distinct CTC subtypes. Individual pt samples were then analyzed for the frequency and heterogeneity (Shannon Index) of CTC subtypes and monitored for clinical endpoints. A subset of CTCs (n = 350) were individually sequenced and analyzed for clonality and CNV to assess genomic heterogeneity. Results: A diversity of CTC phenotypes were observed at each line of therapy. In AR Tx pts, high heterogeneity predicts 6mo PFS (OR = 2.57, p = 0.01) and shorter OS (HR = 4.5, p &lt; 0.001). Separately, specific CTC phenotypes also predict 6mo PFS (OR = 5, p &lt; 0.001) and shorter OS (HR = 5.8, p &lt; 0.001). Heterogeneity scores were not associated with taxane resistance. NGS analysis identified subclonal drivers of disease progression including multiple private and/or clustered genomic drivers. Conclusions: Single CTC characterization of phenotype and genotype supports the concept of tumor heterogeneity as a driver of disease resistance. The heterogeneity observed supports the potential value of single cell characterization to identify rare somatic sub-clonal alterations and can aid in the development of rational therapeutic trials.
Cytochemical Observations on the Adenovirus Type-12-Transformed Hamster-Embryo Cell Cultures&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: George I. Malinin
Journal: JNCI Journal of the National Cancer Institute (1969)

Cytochemical and morphological evaluation of normal hamster-embryo cell monolayers revealed 3 predominant cell types: large epithelioid cells with moderate affinity for RNA stains and no cytochemically demonstrable tyrosine (type 1), and round mononuclear (type 2) and binuclear (type 3) cells characterized by intense staining reactions for RNA, tyrosine, and carbohydrates. Inoculation of the intact cultures with the adenovirus type 12 produced no apparent cytopathic effect the first 5 days. This dormancy interval was followed by an intermediate stage (5–10 days) characterized by karyorrhexis of mainly type 2 and 3 cells, presence of extranuclear DNA particles, and appearance of intercellular hexagonal crystals with DNA cores and, less frequently, by the intranuclear crystalline-like inclusions. Concomitantly, type 1 cells gave rise to the mononucleated giant cells often containing multiple intranuclear “asters.” Type 2 and 3 cells formed transformed colonies characterized by strong staining reactions for proteins, tyrosine, DNA, but not for RNA. The cells, not included into transformed colonies, evolved into granular cytoplasm-type cells containing 0.5–4 μ cytoplasmic granules and a prominent chromophobic Golgi zone. The high cellular levels of RNA and tyrosine-containing proteins may constitute the initial prerequisite for transformation by the adenovirus type 12, whereas the transformed cells depend on DNA and proteins for their growth.
Food industry body admits that voluntary agreements lack punch
Authors: Caroline White
Journal: BMJ (2016)

Voluntary agreements between the UK government and industry to improve the nation’s diet and curb the rising tide of obesity have reached the end of the road and legislation is needed, says a senior figure of the body that represents the country’s major supermarkets and fast food chains.

Speaking in London on 9 March at the Westminster Food and Nutrition Forum on the next steps for obesity policy, Andrea Martinez-Inchausti, deputy director of food policy at the British Retail Consortium, said that retailers understood that they had a role in improving the nation’s health.

Retailers had done “a lot of work” on product reformulation to reduce salt, fat, …
Comparable Allogeneic Hematopoietic Cell Transplantation Outcome Of Haplo-Identical Family Donor With Matched Unrelated/Mismatched Family Donor In Adult Aplastic Anemia
Authors: Hawk Kim, Je-Hwan Lee, Young-Don Joo, Sung-Hwa Bae, Jung-Hee Lee, Dae-Young Kim, Jae-Cheol Jo, Jae Hoo Park, Won Sik Lee, Hun-Mo Ryoo, Sang-Kyu Park, Kyoo Hyung Lee
Journal: Blood (2013)
Talking about cross-talk: the immune system and the microbiome
Authors: David Zeevi, Tal Korem, Eran Segal
Journal: Genome biology (2016)

A report on the first EMBO conference entitled "Next Gen Immunology-From Host Genome to the Microbiome: Immunity in the Genomic Era", held at the Weizmann Institute of Science, Israel, 14-16 February, 2016.
Abstract 16380: Bosentan Inhibits Proliferation of Cells Isolated from Patients with Chronic Thromboembolic Pulmonary Hypertension
Authors: Aiko Ogawa, Kazufumi Nakamura, Satoshi Akagi, Kengo F Kusano, Hiroshi Ito
Journal: Circulation (2010)

Background: Chronic thromboembolic pulmonary hypertension (CTEPH) develops in about 4% of patients with acute pulmonary thromboembolism. About 50% of CTEPH patients are inoperable or suffering from...
Abnormal Glomerular Basement Membrane Laminins in Murine, Canine, and Human Alport Syndrome
Authors: CLIFFORD E. KASHTAN, YOUNGKI KIM, GEORGE E. LEES, PAUL S. THORNER, ISMO VIRTANEN, JEFFREY H. MINER
Journal: Journal of the American Society of Nephrology (2001)

Abstract. Kidneys from mice, dogs, and humans with X-linked and autosomal-recessive forms of Alport syndrome were examined by immunofluorescence for expression of laminin α, β, and γ chains using monospecific antibodies. Laminin α2 chain was absent from glomerular basement membranes (GBM) in normal human, murine, and canine kidneys but was abnormally deposited in Alport GBM, regardless of species or inheritance pattern. In murine and canine Alport kidneys, laminin α2 seems to be deposited as part of both laminin-2 (α2β1γ1) and laminin-4 (α2β2γ1) but as part of only laminin-4 in human Alport kidneys. GBM laminin α2 chain deposition was not observed in a variety of non-Alport human glomerulopathies. This finding adds to the list of proteins that are aberrantly deposited in Alport GBM as a consequence of the absence of the α3, α4, and α5 chains of type IV collagen: ( 1 ) type IV collagen α1 and α2 chains, ( 2 ) type V collagen, ( 3 ) type VI collagen, and most recently ( 4 ) the laminin α2 chain and ( 5 ) the laminin α1 and β1 chains in mice and dogs. These findings emphasize further the critical role played by the α3, α4, and α5 chains of type IV collagen in establishing and maintaining the composition, structure, and function of mature GBM.
Four Different Phenotypes of Bhr Changing Pattern in School Children and It's Risk Factors
Authors: Young-Ho Kim, Eun Lee, Song-I. Yang, Hyun-Ju Cho, Hyung-Young Kim, Ji-Won Kwon, Young Ho Jung, Byoung-Ju Kim, Ju-Hee Seo, Hyo-Bin Kim, So-Yeon Lee, Ho-Jang Kwon, Soo-Jong Hong
Journal: Journal of Allergy and Clinical Immunology (2016)
Selection and In Vivo Properties of Lectin-Attachment Variants of Malignant Murine Lymphosarcoma Cell Lines&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: C L Reading, P N Belloni, G L Nicolson
Journal: JNCI Journal of the National Cancer Institute (1980)

Variants of malignant RAW117 lymphosarcoma cell lines were selected by sequential nonadherence to polystyrene-immobilized lectins. Parental murine lymphosarcoma line RAW-117-P grew in suspension and was rapidly bound by immobilized concanavalin A (Con A), Rlclnus communis agglutinin I (RCA1), peanut agglutinin (PNA), or wheat germ agglutinin (WGA). After attachment of most cells to lectin-substituted petri dishes, the unattached cells (<1%) were removed by aspiration and subcultured. Selection by nonadherence to immobilized lectins was repeated seven to ten times, and the resulting cell lines were tested in BALB/c mice to determine their malignant potentials. Parental line RAW117-P formed few (median, 0; range, 0-20) liver tumor colonies per 5×103 iv injected cells after 14 days, whereas a variant line selected ten times on immobilized Con A (RAW117-P Con Aa1c) formed a median of 95 (range, 9->200) liver colonies. RAW117-P cells selected by nonadherence on immobilized WGA, PNA, or RCAI showed no increase in liver tumor formation compared to the cells of the parental line. In contrast, RAW117-H10, a variant line selected ten times in vivo for liver colonization, formed more than 200 liver tumor colonies, and selection eight times on immobilized WGA yielded a line (RAW117-H10 WGAa8) that formed a median of only 1 (range, 0–4) tumor colony. Variants of the RAW117-H10 line selected on immobilized RCAI, Con A, or PNA still formed more than 200 liver tumor colonies.125l-labeled lectin-binding studies indicated decreased lectin-binding sites on the in vivo and some of the immobilized lectin-selected lines. Autoradiographs of125l-labeled Con A-stained sodium dodecyl sulfate polyacrylamide gels showed a decrease in the major Con A-staining band (mol wt, ≈70,000) in the in vivo and immobilized Con A-selected lines. These studies indicated that alterations in cell surface lectin receptors could modify in vivo malignant behavior.
Association of decreased expression of protein phosphatase 2A subunit PR55γ (PPP2R2C) with an increased risk of metastases and prostate cancer-specific mortality.
Authors: Elysia Sophia Spencer, Eric Gregory Bluemn, Richard Johnston, Xiaotun Zhang, Ryan Robert Gordon, Daniel Lewinshtein, Jared Lucas, Peter Nelson, Christopher R. Porter
Journal: Journal of Clinical Oncology (2012)

4669 Background: The protein phosphatase 2A (PP2A) holoenzyme complex negatively controls cell growth, differentiation and apoptosis. Down regulation of PP2A activity is associated with oncogenic transformation of papillomas and is a target for the small-T viral oncogene. The PR55γ (2R2C) subunit regulates PP2A target specificity, inhibiting c-Src activity in some cell lines. c-Src activity enhances growth and invasion in prostate cancer. This study evaluates whether PPP2R2C protein levels in radical prostatectomy (RP) specimens were predictive for the development of metastases or prostate-cancer specific mortality (PCSM). Methods: From 1954-1997, 1004 consecutive patients underwent RP at Virginia Mason Medical Center in Seattle. Metastases were confirmed radiographically or by tissue diagnosis. Death certificates confirmed PCSM. Patients without stored tissue were excluded. 34 patients with metastases or PCSM were matched to patients without recurrence (NR) at a 1:2 ratio. Paraffin-embedded tissue was stained with anti-PPP2R2C monoclonal antibody, clone 6D1 (Abnova, Taiwan). A pathologist evaluated the percentage and intensity of nuclei stained using a 4-point scale. Statistical analysis was performed on SAS. Results: Mean follow up was 10.26 years. PPP2R2C was detected in 13/18 (72.2%) PCSM, 18/22 (81.8%) metastases and 45/49 (91.8%) NR patients. Mean expression was lower in cancerous vs benign glands, 1.74 vs 2.04 (p = 0.001). Expression intensity from PCSM vs NR was 1.45 vs 1.80 (p = 0.041). On multivariate analysis, expression was lower in metastases or PCSM versus NR 1.79 vs 2.35 (p = 0.002), independent of pre-op PSA and Gleason grade. Conclusions: PPP2R2C loss was highly correlated with metastasis and PCSM. Patients with the lowest levels of expression were at the highest risk for PCSM. As tissue was obtained at time of surgery, this analysis reflects a truly prognostic biomarker, independent of Gleason grade and PSA. We have shown that PPP2R2C scoring is a useful metric to identify patients at high risk of developing advanced disease. With further validation may allow for more accurate individual patient treatment plans and counseling.
Prevalence and risk factors of vitamin D insufficiency in cancer
Authors: K. A. Hauser, M. Karafa, D. Seyidova-Khoshknabi, M. P. Davis, D. Walsh
Journal: Journal of Clinical Oncology (2009)

9581 Background: Low vitamin D has been linked to increased cancer incidence and reduced prognosis. Little is known about prevalence and risks of insufficiency in cancer. Methods: Electronic medical records of all adult solid tumor patients treated at The Cleveland Clinic in 2006–2007 were reviewed. Data extracted: demographics (age, gender, race), cancer site (primary and metastatic, ICD-9 codes) and first 25 hydroxy vitamin D level [25OHD] during the study period. Laboratory data (calcium, hepatic and renal function), medications prescribed (anticonvulsants, antineoplastic, corticosteroids, vitamin D) and treatment procedures (chemotherapy and radiotherapy) in 2 months preceding vitamin D were recorded. Clinical factors were compared between those tested for 25OHD vs not, and those insufficient (25OH D ≤30ng/ml) vs not (25OH D &gt;31ng/ml) by Chi square or T-tests. Stepwise logistic regression identified independent predictors of vitamin D insufficiency. Results: n=39,254. 19,030 (48%) were female, mean age 63 (± 14), 86% Caucasian. Most common cancers: breast (19%), prostate (18%), skin (13%). 2,100 (5%) had vitamin D tested. They were more likely female (66% vs 47%), and to have breast, hepatobiliary, skin or thyroid cancer, than those not tested (both p&lt;0.001). 1446 (69%) were insufficient, and 200 (10%) were frankly deficient (25OHD ≤12ng/ml). Insufficiency was associated with male gender, race (African American), month of test (Feb-Apr, Oct), cancer type (hepatobiliary, genitourinary, pancreas, upper gastrointestinal), metastatic disease, low albumin, high bilirubin and AST, and lack of antineoplastic or vitamin D medication (all p&lt;0.01). Multivariable predictors were cancer type, test month, African American race, low albumin, and lack of antineoplastic or vitamin D medication (all p&lt;0.01). Conclusions: Vitamin D insufficiency is highly prevalent among cancer patients tested. This study is limited by selection bias but indicates need for prospective vitamin D evaluation in cancer. No significant financial relationships to disclose.
Abstract 15154: Effect of Continuous-Flow Mechanical Support on Microvasculature Remodeling may Contribute Adversely to Bridge to Recovery in the Failing Heart
Authors: Tetsuya Saito, Shigeru Miyagawa, Hiroyuki Nishi, Yasushi Yoshikawa, Satsuki Fukushima, Daisuke Yoshioka, Akima Harada, Koichi Toda, Yoshiki Sawa
Journal: Circulation (2012)

Introduction: Left ventricle (LV) unloading using a left ventricular assist device (LVAD) has been shown to enhance reverse LV remodeling. Despite the increasing need for its usage, the direct effect of continuous-flow LVAD with decreased pulsatility and shear stress on microvasculature is unknown. We examined that pulseless continuous flow may affect myocardial microvasculature and remodeling of the failing heart. Methods: The study included 24 patients with chronic heart failure who underwent LVAD implantation. Pulsatile-flow LVAD was used in 11 patients (P group) with a median support period of 954 days, whereas continuous-flow LVAD was used in 13 patients (C group) with a median support period of 709 days. Serial echocardiograms were compared between the 2 groups. Transmural LV tissues were sampled during both the implantation and explantation of the LVAD in all patients for histopathological assessment including immunolabeling for CD31 and α-smooth muscle actin (SMA). Results: Echocardiography showed...
Electrocardiographic Early Repolarization
Authors: Kristen K. Patton, Patrick T. Ellinor, Michael Ezekowitz, Peter Kowey, Steven A. Lubitz, Marco Perez, Jonathan Piccini, Mintu Turakhia, Paul Wang, Sami Viskin
Journal: Circulation (2016)

The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship
Factors Affecting Control and Adherence to One Year Treatment in Elderly Asthmatics in Turkey
Authors: Bilun Gemicioglu, Hasan Bayram, Arif Cimrin, Oznur Abadoglu, Aykut Cilli, Esra Uzaslan, Hakan Gunen, Levent Akyildiz, Mecit Suerdem, Tevfik Ozlu, Zeynep Misirligil
Journal: Journal of Allergy and Clinical Immunology (2016)
Prospective evaluation of serum tissue inhibitor of metalloproteinase-1 (TIMP-1) and carbonic anhydrase IX (CAIX) in correlation to circulating tumor cells in patients with metastatic breast cancer.
Authors: T. N. Fehm, B. K. Rack, W. Janni, P. A. Fasching, J. Zeitz, E. Solomayer, B. Aktas, S. Kasimir-Bauer, K. Pantel, V. Mueller
Journal: Journal of Clinical Oncology (2010)

1153 Background: Circulating tumor cells (CTC) reflect aggressive tumor behavior by hematogenus tumor cell dissemination in patients with breast cancer. The tissue inhibitor of metalloproteinase 1 (TIMP-1) plays a role in tissue invasion and angiogenesis. Carbonic anhydrase IX (CAIX) is a metalloenzym involved in cell adhesion, growth, and survival of tumor cells. The aim of this study was therefore to investigate the role of TIMP1 and CAIX levels and their association with the presence of CTC in metastatic breast cancer. Methods: Serum was obtained in a prospective multicenter setting from 253 pts with metastatic breast cancer at the time of disease progression. Serum TIMP-1 and CAIX were determined using commercial ELISA-kits (Oncogene Science). CTC were detected with the CellSearch system (Veridex) with a cut off of 5 or more cells. Results: Five or more CTC were detected in 122 of 245 evaluable pts. Seventy of 253 (28%) metastatic pts had elevated serum TIMP-1 levels above 454 ng/mL. Serum CAIX was elevated above 506ng/mL in 90 (35%) pts. Both serum markers had prognostic significance. Median PFS was 6 mo in pts with elevated TIMP-1 versus 10 mo in those with nonelevated levels (p=0.01). OS was 6 mo vs. 11 mo (p< 0.01). Median PFS was 7 mo in pts with elevated CAIX versus 10 mo in those with nonelevated levels. OS was 13 mo vs. 16 mo (p<0.01). In pts. with ≥5 CTC, serum levels were above the cut off for CAIX in 47% vs. 25% in those with less than 5 CTC (p=0.01). For TIMP-1, 37% pts. with ≥5 CTC had elevated CAIX serum levels and 17%, with less than 5 CTC (p=0.01). Including TIMP-1, CAIX, and established prognostic factors in the multivariate analysis, (site of metastatic disease, ER, PR, HER2, therapy-line, and extent of metastatic disease) only the presence of CTC remained an independent predictor of both OS and PFS. Conclusions: Our study demonstrates with a prospective design that serum TIMP-1 and CAIX have prognostic impact in metastatic breast cancer and that elevated serum levels of these invasion markers are associated with presence of CTC. Their influence on hematogeneous tumor cell dissemination has to be further elucidated. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Roche Roche, Veridex
Final Results of a Randomized Phase Ii Study with Neo-Adjuvant Triplet or Doublet Therapy, Radiation and Total Mesorectal Excision for Locally Advanced Rectal Cancer: Axe Beam
Authors: G. Chiritescu, K. Dumon, P. Vergauwe, J. Arts, L. Verbeke, M. Polus, Y. Humblet, J. van Laethem, J. Daisne, J. Decaestecker, A. D'Hoore, F. Mardjuadi, A. Debucquoy, M. Verstraete, X. Sagaert, K. Haustermans, E. Van Cutsem
Journal: Annals of Oncology (2014)
Long-Acting Reversible Contraception and Condom Use Among Female US High School Students
Authors: Riley J. Steiner, Nicole Liddon, Andrea L. Swartzendruber, Catherine N. Rasberry, Jessica M. Sales
Journal: JAMA Pediatrics (2016)

Long-acting reversible contraception (LARC), specifically intrauterine devices and implants, offers an unprecedented opportunity to reduce unintended pregnancies among adolescents because it is highly effective even with typical use. However, adolescent LARC users may be less likely to use condoms for preventing sexually transmitted infections compared with users of moderately effective contraceptive methods (ie, oral, Depo-Provera injection, patch, and ring contraceptives).To compare condom use between sexually active female LARC users and users of moderately effective contraceptive methods.Cross-sectional analysis using data from the 2013 national Youth Risk Behavior Survey, a nationally representative sample of US high school students in grades 9 through 12. Descriptive analyses were conducted among sexually active female students (n = 2288); logistic regression analyses were restricted to sexually active female users of LARC and moderately effective contraception (n = 619). The analyses were conducted in July and August 2015.Contraceptive method at last sexual intercourse was assessed by 1 item-respondents could select birth control pills; condoms; an intrauterine device or implant; injection, patch, or ring; withdrawal or other method; or not sure. A separate item asked whether respondents used a condom at last sexual intercourse. We created an indicator variable to distinguish those reporting use of (1) LARC (intrauterine device or implant), (2) oral contraceptives, and (3) Depo-Provera, patch, or ring.Among the 2288 sexually active female participants (56.7% white; 33.6% in 12th grade), 1.8% used LARC; 5.7% used Depo-Provera, patch, or ring; 22.4% used oral contraceptives; 40.8% used condoms; 11.8% used withdrawal or other method; 15.7% used no contraceptive method; and 1.9% were not sure. In adjusted analyses, LARC users were about 60% less likely to use condoms compared with oral contraceptive users (adjusted prevalence ratio [aPR], 0.42; 95% CI, 0.21-0.84). No significant differences in condom use were observed between LARC users and Depo-Provera injection, patch, or ring users (aPR, 0.57; 95% CI, 0.26-1.25). The LARC users were more than twice as likely to have 2 or more recent sexual partners compared with oral contraceptive users (aPR, 2.61; 95% CI, 1.75-3.90) and Depo-Provera, patch, or ring users (aPR, 2.58; 95% CI, 1.17-5.67).Observed differences in condom use may reflect motivations to use condoms for backup pregnancy prevention. Users of highly effective LARC methods may no longer perceive a need for condoms even if they have multiple sexual partners, which places them at risk for sexually transmitted infections. As uptake of LARC increases among adolescents, a clear need exists to incorporate messages about condom use specifically for sexually transmitted infection prevention.