tbuckley/cabot-search huggingface dataset:
Antidepressant use and cardiovascular risk: moving from emotive rhetoric towards evidence based care
Authors: Vlad Schlezak, Kripalani Mukesh
Journal: BMJ (2016)

When many psychiatrists are struggling to engage patients with protocols for physical health monitoring, we welcome the idea that antidepressant prescribing is safe when indicated.1 These findings counter media claims about increased numbers of prescriptions for antidepressants in the UK2 and suggestions from psychologists that …
High prevalence and allele burden-independent prognostic importance of p53 mutations in an inner-city MDS/AML cohort
Authors: S Goel, J Hall, K Pradhan, C Hirsch, B Przychodzen, A Shastri, I Mantzaris, M Janakiram, R Battini, N Kornblum, O Derman, K Gritsman, J Al-Hafidh, Y Wang, B Halmos, U Steidl, J P Maciejewski, I Braunschweig, A Verma
Journal: Leukemia (2016)
Pooling across cells to normalize single-cell RNA sequencing data with many zero counts
Authors: Aaron T. L. Lun, Karsten Bach, John C. Marioni
Journal: Genome biology (2016)

Normalization of single-cell RNA sequencing data is necessary to eliminate cell-specific biases prior to downstream analyses. However, this is not straightforward for noisy single-cell data where many counts are zero. We present a novel approach where expression values are summed across pools of cells, and the summed values are used for normalization. Pool-based size factors are then deconvolved to yield cell-based factors. Our deconvolution approach outperforms existing methods for accurate normalization of cell-specific biases in simulated data. Similar behavior is observed in real data, where deconvolution improves the relevance of results of downstream analyses.
Abstract P5-01-01: Real-time imaging of lymph node metastasis in response to systemic ezrin inhibitor treatment in breast cancer
Authors: A Ghaffari, V Hoskin, G Mullins, P Greer, F Kiefer, Y Madarnas, S SenGupta, B Elliott
Journal: Cancer Research (2016)

Abstract Lymph node (LN) metastasis is a key driver of recurrence and survival in breast cancer (BC) patients. However, the mechanisms of metastatic dissemination of tumour cells from LNs to distant sites and their predictors of response to systemic therapy remain poorly understood, mainly due to a lack of non-invasive in vivo imaging models. We have recently described ezrin, a pro-metastatic crosslinker protein, as a regulator of tumour lymphangiogenesis and metastasis in BC (Breast Cancer Res. 2014; 16(5): 438). Furthermore, we demonstrated significant association of high ezrin expression with lymphovascular invasion in a cohort (n=63) of premenopausal patients with invasive BC (p =0.024). These findings prompted us to examine the role of ezrin in migration and invasion of metastatic tumour cells in LNs and their response to ezrin-targeted therapy. Using a locally accrued LN positive patient cohort (n=94), we demonstrated a significant association between high ezrin levels and reduced recurrence-free survival (univariate Log-rank test, p=0.033), suggesting that ezrin is a potential predictor of relapse in LN positive BC. To address the mechanistic role of ezrin in LN metastasis, we developed a novel intravital imaging model using a lymphatic reporter transgenic mouse (B6-prox1-mOrange2-pA-BAC) to examine the response of tumour-draining LN to anti-ezrin systemic therapy in real time. Next, we tested the effects of a small molecule ezrin inhibitor (NSC668394) in vitro and observed significant suppression of ezrin activation (p-T567) and cancer cell invasive phenotype. Intravital imaging of inguinal LN metastases, derived from subcutaneously implanted breast adenocarcinoma E0771-LMV (lung metastatic variant) cells, demonstrated significant reduction in mobility and invasiveness (Mann Whitney, p&amp;lt;0.0001) of metastatic cells following systemic treatment with NSC668394 (0.5 mg/kg at 24h and 8h prior to imaging). Interestingly, LN metastases engagement by host T cell (CD3+) was notably increased, whereas T cell mobility was not affected by ezrin inhibition. Our findings present a novel non-invasive imaging model to study the LN metastasis response to anti-cancer therapy in real time, and provide new insight into the role of ezrin as a potential anti-metastatic target in BC. (Supported by CRS, CIHR, CBCF, BCAK, Queen's SRC). Citation Format: Ghaffari A, Hoskin V, Mullins G, Greer P, Kiefer F, Madarnas Y, SenGupta S, Elliott B. Real-time imaging of lymph node metastasis in response to systemic ezrin inhibitor treatment in breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-01-01.
Inhibition of Recovery From Bleomycin-Induced Potentially Lethal Damage 2
Authors: S. C. Barranco, B. R. Haenelt, W. E. Bolton
Journal: JNCI Journal of the National Cancer Institute (1977)

Mammalian cells are able to recover from bleomycin (Bleo)-induced potentially lethal damage. We examined the influences of inhibitors of DNA, RNA, or protein synthesis on that recovery. Cytosine arabinoside and cycloheximide did not inhibit recovery from Bleo-induced damage; however, actinomycin D (Act D) did inhibit it. At a dose that produced minimal cell killing and inhibited only RNA synthesis, inhibition of recovery by Act D was immediate and complete.
A phase 2, randomized, open-label study of lucitanib in patients with FGF aberrant metastatic breast cancer.
Authors: Maysa M. Abu-Khalaf, Ingrid A. Mayer, Chris Tankersley, Jadine Moy, Andrew R. Allen, Charles L. Vogel, Frankie Ann Holmes, Rita Nanda, Kathy Miller, Ravindranath Patel, Lajos Pusztai, Carlos L. Arteaga
Journal: Journal of Clinical Oncology (2015)

TPS628 Background: Lucitanib is a potent, oral inhibitor of the tyrosine kinase activity of Fibroblast Growth Factor Receptors 1-3 (FGFR1-3), Vascular Endothelial Growth Factor Receptors 1-3 (VEGFR1-3) and Platelet-Derived Growth Factor Receptors α/β (PDGFRα/β). FGF aberrancy is a hallmark genomic alteration observed in up to 25% of patients with breast cancer and is defined by amplification of FGFR1, and or 11q (containing FGF ligands 3, 4, 19, and CyclinD1). In a recent phase 1/2 clinical trial of lucitanib at daily doses of 5 to 20 mg, heavily pretreated patients with advanced breast cancer patients and FGF aberrancy experienced an objective response rate (ORR) of 50% and a median progression-free survival (PFS) of over 9 months (Soria et al, 2014). This compelling clinical activity has led to the initiation of a global clinical development program for lucitanib in breast cancer. Methods: The current phase 2 study was designed to evaluate the efficacy and safety of 2 different doses (10 and 15 mg) of l...
P0356 : Circulating free tumour DNA concentration is a more useful diagnostic marker than TP53 mutation detection in HBV-related HCC in West African patients
Authors: S. Knapp, J. Howell, Y. Sherwani, M. Shariff, L. Karanfilian, N. Ladep, E. Okeke, S. Taylor-Robinson, M. Thursz
Journal: Journal of Hepatology (2015)
Phase I study of intranodal direct injection of adenovirus encoding recombinant CD40-ligand (Ad-ISF35) in patients with chronic lymphocytic leukemia
Authors: J. E. Castro, J. D. Sandoval-Sus, J. Melo-Cardenas, D. Darrah, M. Urquiza, R. S. Pakbaz, C. E. Prussak, T. J. Kipps
Journal: Journal of Clinical Oncology (2009)

3003 Background: Transduction of chronic lymphocytic leukemia (CLL) cells with replication-defective adenovirus (Ad) encoding a genetically engineered, membrane-stablized CD154 (ISF35) converts transduced, and “bystander” non-transduced, CLL cells into proficient antigen presenting cells that can induce immunity against autologous leukemia cells. Preclinical studies demonstrated that direct injection of Ad-ISF35 into lymphoma nodules can induce potent anti-lymphoma immune responses in test animals, capable of eradicating lethal tumors at distal sites and protect against recurrent disease upon subsequent re-challenge with syngeneic tumor. Methods: We conducted a phase I study on 15 patients to evaluate the safety of intranodal direct injection (IDI) of Ad-ISF35. Pts, ages 45–71 yrs, with rapidly progressive disease (median CLL doubling time of 3.7 months) each received a single ultrasound guided IDI of 1 to 30 x 10 10 Ad-ISF35 viral particles in 4 different dose cohorts. Results: IDI of Ad-ISF35 was well-tolerated and effective in inducing systemic responses. Some pts had grade ≤ 2 injection-site erythema, pain and/or swelling, or flu-like symptoms. Some pts in the highest-dose cohorts had transient, asymptomatic grade 3/4 hypophosphatemia. No long-term (≥ 6 wk) adverse effects were observed. Although there was no evidence for dissemination of Ad-ISF35 beyond the injected lymph node, IDI of Ad-ISF35 induced blood CLL cells to express death receptors, pro-apoptotic proteins, and immune co-stimulatory molecules similar to those induced on “bystander” CLL cells co-cultured with Ad-ISF35 transduced cells in vitro. Importantly, IDI of Ad-ISF35 resulted in significant reductions in blood leukemia cell counts and a median reduction of 53.2% (range 25–75.4%) in the size of lymph nodes and/or spleen, which was durable (≥ 4 months) in 9 pts. Despite aggressive disease prior to treatment, the median treatment-free survival was 5.3 months and 3 pts have yet to require additional treatment after 1-year follow-up. Conclusions: Single IDI of Ad-ISF35 was safe and effective in inducing systemic biologic and clinical responses in pts with CLL. IDI of Ad-ISF35 might be effective in the treatment of CLL and related lymphomas. [Table: see text]
Proton Pump Inhibitors (PPIs) May Modulate More Than Just Reflux in Chronic Rhinosinusitis with Nasal Polyps
Authors: Jin Young Min, Robert C. Kern, Christopher J. Ocampo, Whitney W. Stevens, Caroline P.E. Price, Christopher F. Thompson, Tetsuya Homma, David B. Conley, Stephanie Shintani-Smith, Julia H. Huang, Lydia Suh, James E. Norton, Kathryn E. Hulse, Atsushi Kato, Robert P. Schleimer, Bruce K. Tan
Journal: Journal of Allergy and Clinical Immunology (2016)

Chronic rhinosinusitis with nasal polyps (CRSwNP) is frequently characterized by tissue eosinophilia but the relationship of eosinophilia to other type 2 biomarkers has not been explored. Furthermore, recent data suggesting PPIs modulate eotaxin-3 production in eosinophilic esophagitis may have therapeutic implications for CRSwNP. We sought to characterize levels of type 2 mediators and their relationship to tissue eosinophilia and radiographic severity in CRS. We further aimed to evaluate whether PPIs have therapeutic potential in CRS and identify possible mechanisms of action in airway epithelium. Type 2 mediators in nasal tissue and lavage fluid from control and CRS patients were measured by Luminex assay. Human sinonasal epithelial cells and BEAS-2B cells were stimulated with IL-13 in the presence and absence of PPIs. The effects of PPIs on IL-13-induced effects were measured by ELISA, qRT-PCR, and pH imaging. IL-13, eotaxin-2 and eotaxin-3 were highly elevated in CRSwNP compared to control and were correlated with tissue ECP and radiographic severity. CRS patients taking PPIs had significantly lower tissue eotaxin-2 and eotaxin-3 levels than those not taking PPIs. In vitro, 5 different PPIs and the competitive H+/K+-ATPase inhibitor SCH-28080 all significantly inhibited IL-13-induced eotaxin-3 release by airway epithelial cells. In addition, IL-13-induced eotaxin-3 expression was dependent on the presence of extracellular K+ and associated with a PPI sensitive efflux of H+ions. IL-13, eotaxin-2, and eotaxin-3 in tissue are potential biomarkers of eosinophilia and severity in CRSwNP. Inhibition of IL-13-induced eotaxin-3 by PPIs may provide therapeutic benefit in CRSwNP via a novel H+/K+-dependent mechanism.
Novel Therapeutic Approach To Graft-Versus-Host Disease With Allele-Specific Anti-HLA Monoclonal Antibody
Authors: Yusuke Nakauchi, Satoshi Yamazaki, Stephanie Carlisle Napier, Jo-ichi Usui, Yasunori Ota, Satoshi Takahashi, Nobukazu Watanabe, Hiromitsu Nakauchi
Journal: Blood (2013)
Mimicking Tissue Boundaries by Sharp Multiparameter Matrix Interfaces
Authors: Jiranuwat Sapudom, Stefan Rubner, Steve Martin, Tilo Pompe
Journal: Advanced Healthcare Materials (2016)

Engineering interfaces of distinct extracellular compartments mimicking native tissues are key for in-depth in vitro studies on developmental and disease processes in biology and medicine. Sharp interfaces of extracellular matrices are constructed based on fibrillar collagen I networks with a multiparameter control of topology, mechanics, and composition, and their distinct impact on triggering the directionality of cancer cell migration is demonstrated. As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re-organized for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
The “Pain Matrix” in Pain-Free Individuals
Authors: Tim V. Salomons, Gian Domenico Iannetti, Meng Liang, John N. Wood
Journal: JAMA Neurology (2016)

Human functional imaging provides a correlative picture of brain activity during pain. A particular set of central nervous system structures (eg, the anterior cingulate cortex, thalamus, and insula) consistently respond to transient nociceptive stimuli causing pain. Activation of this so-called pain matrix or pain signature has been related to perceived pain intensity, both within and between individuals,1,2 and is now considered a candidate biomarker for pain in medicolegal settings and a tool for drug discovery. The pain-specific interpretation of such functional magnetic resonance imaging (fMRI) responses, although logically flawed,3,4 remains pervasive. For example, a 2015 review states that “the most likely interpretation of activity in the pain matrix seems to be pain.”4 Demonstrating the nonspecificity of the pain matrix requires ruling out the presence of pain when highly salient sensory stimuli are presented. In this study, we administered noxious mechanical stimuli to individuals with congenital insensitivity to pain and sampled their brain activity with fMRI. Loss-of-function SCN9A mutations in these individuals abolishes sensory neuron sodium channel Nav1.7 activity, resulting in pain insensitivity through an impaired peripheral drive that leaves tactile percepts fully intact.5 This allows complete experimental disambiguation of sensory responses and painful sensations
Carcinoma of the Lung with Inappropriate Antidiuresis
Authors: Thomas T. Amatruda, Patrick J. Mulrow, John C. Gallagher, Wilbur H. Sawyer
Journal: New England Journal of Medicine (1963)

THE association of carcinoma of the lung with hyponatremiaand renal sodium loss has been reported on several occasions. Schwartz et al.1 first demonstrated the presence of inappropriate antidiuresis in patients with this syndrome and suggested that it was due to inappropriate secretion of antidiuretic hormone. There have been no reports of elevated levels of vasopressin in the blood of such patients. Even in maximal antidiuresis, however, peripheral blood concentrations of vasopressin could easily escape detection by presently available methods for extraction and biologic assay. The pathogenesis of the syndrome has been obscure, but a neurogenic basis due to involvement of . . .
A Childhood Leukaemia Cluster in Milan: Possible Role of Pandemic AH1N1 Swine Flu Virus.
Authors: Giovanni Cazzaniga, Luigi A. Bisanti, Chiara Palmi, Giorgia Randi, Fabrizio Pregliasco, Silvia Deandrea, Silvia Bungaro, Maria Grazia Valsecchi, Giuseppe Masera, Andrea Biondi, Mel Greaves
Journal: Blood (2012)
Somatic <i>DICER1</i> mutations in adult-onset pulmonary blastoma
Authors: Leanne de Kock, Ismaël Bah, Joan Brunet, Harriet Druker, Itziar Astigarraga, Joaquim Bosch-Barrera, Dorothée Bouron-Dal Soglio, Van-Hung Nguyen, David Malkin, John R. Priest, William D. Foulkes
Journal: European Respiratory Journal (2016)

Several rare lung tumours morphologically mimic embryonal structures of the developing human lung. Historically, these blastomatous tumours were described under the umbrella term of pulmonary blastoma. Subsequently, distinct entities were recognised, such as childhood pleuropulmonary blastoma (PPB) \[1\] (International Classification of Diseases for Oncology (ICD-O-3) code 8973/3). Later, adult-onset pulmonary blastoma was separated into well-differentiated fetal adenocarcinoma (WDFA) (ICD 8333/3) and pulmonary blastoma (ICD 8972/3) [2]. Pulmonary blastoma is a biphasic epithelial and mesenchymal malignancy, whereas PPB is purely sarcomatous and WDFA is characterised by a monophasic immature epithelium. Since 1988, the childhood PPB has received particular attention because of 1) its unique developmental progression from relatively indolent neonatal-onset lung cysts, to aggressive cystic-solid and solid sarcomas by age 72 months; 2) PPB's status heralding a newly recognised familial tumour predisposition syndrome and 3) its strong association with both germ-line and somatic DICER1 mutations, which is not only true for PPB, but also for many other tumours in pleiotropic predisposition syndrome (now referred to as DICER1 syndrome). Until recently, neither WDFA nor pulmonary blastoma had been observed in families manifesting DICER1 syndrome [3]. However, in 2015, we identified a second somatic DICER1 RNase IIIb mutation [4] in a WDFA that arose in a 16-year-old germ-line DICER1 mutation carrier [5]. In addition to DICER1 mutations in PPB and WDFA, somatic CTNNB1 mutations (encoding β-catenin) appear to characterise WDFA and pulmonary blastoma [6], and are far less frequent in PPB [7, 8]. In contrast, TP53 mutations are found in both PPB [8] and pulmonary blastoma [9], but not WDFA [9]. We identified two somatic DICER1 mutations in each of two adult pulmonary blastomas, implicating DICER1 in causation <http://ow.ly/10aM9V> We thank Talia Boshari (Lady Davis Institute, Jewish General Hospital, Montreal, QC, Canada) for help with sample acquisition and associated administrative work and Naciba Benlimame (George and Olga Minarik Research Pathology Facility, Jewish General Hospital, Montreal, QC, Canada) for help with IHC staining. We also thank Richard Hung (St Joseph's Health Centre, Toronto, ON, Canada) for performing the initial pathology review on case 1.
Is Anastrozole Superior to Tamoxifen as First-Line Therapy for Advanced Breast Cancer?: Letter 3
Authors: Charles M. Bagley, Ronald K. Rowbotham
Journal: Journal of Clinical Oncology (2001)

Article Tools SPECIAL DEPARTMENTS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2001.19.9.2578 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 11331342 Is Anastrozole Superior to Tamoxifen as First-Line Therapy for Advanced Breast Cancer?: Letter 3 Charles M. Bagley JrxCharles M. Bagley JrSearch for articles by this author , Ronald K. RowbothamxRonald K. RowbothamSearch for articles by this author Show More Puget Sound Cancer Centers, Seattle, WANorthwest Hospital, Seattle, WA https://doi.org/10.1200/JCO.2001.19.9.2578 First Page Full Text PDF Figures and Tables © 2001 by American Society of Clinical Oncology
CXCR4, EGFR and HER2 expression in patients with high-risk synovial sarcoma (SS): A clinicopathologic study
Authors: S. Grisanti, E. Rossi, L. Ardighieri, C. Farisoglio, V. D. Ferrari, L. Bercich, E. Simoncini, G. Marini, F. Facchetti
Journal: Journal of Clinical Oncology (2006)

9580 Background: CXCR4 is overexpressed in many human tumors and plays important role in targeted metastasis. CXCR4 activation has been described in osteosarcoma, rhabdomyosarcoma and Ewing’s sarcoma both in vivo and in vitro, but its role has not been elucidated in SS yet. EGFR and Her2/neu, have been described to be overexpressed in patients with SS and proposed as potential therapeutic targets. Because CXCR4 and Her2 have been found to be functionally linked in breast cancer cell lines, we characterized SS in terms of CXCR4, Her2 and EGFR coexpression. Materials and Methods: Six patients sequentially observed at the Spedali Civili di Brescia from 1999 to 2005, with a diagnosis of synovial sarcoma were included in the study. The diagnosis of SS, a FISH analysis for t(X;18) was performed by using a commercial probe specific for the SYT gene breakpoint region (18q11) or by RT-PCR. Her2 and EGFR expression were determined by IHC and Her2 gene amplification by FISH analysis. CXCR4 expression was determined by IHC with anti-human CXCR4 monoclonal antibody (Clone 44716, R&amp;D Systems) followed by incubation with the EnVision peroxidase kit (Dakocytomation, Glostrup, Denmark). Results: All patients were classified high-risk (stage III-IV) according to the AJCC/UICC VI Edition Staging System for soft tissue sarcomas. In all samples IHC analysis for Her2 was negative and no amplification was found by FISH. EGFR staining demonstrated positivity in 5 patients out of 6. CXCR4 reactivity was identified in 4 cases (nuclear staining in 3 and membrane staining in 1). CXCR4 and EGFR were coexpressed in 3 tumors. After a median follow-up of 24 months, 2 patients are dead of SS, 4 patients are alive, 3 of them are disease-free and one relapsed to the lung. The 3 patients alive and disease-free resulted positive for nuclear CXCR4 and EGFR while membrane CXCR4 was expressed in one dead patient. Conclusion: This study provides evidence that CXCR4 is expressed in cases of SS and is frequently coexpressed with EGFR but not with Her2. Due to the small size of this series it is not possible to establish any definitive prognostic or predictive value of CXCR4. However, nuclear expression of CXCR4 seems to be associated with a more indolent behaviour of the tumor and requires confirmation in larger series. No significant financial relationships to disclose.
Human Papillomavirus Vaccination Coverage Among School Girls in a Demonstration Project — Botswana, 2013
Authors: Mmakgomo Mimi Raesima, Sara E. Forhan, Andrew C. Voetsch, Shannon Hewitt, Susan Hariri, Susan A. Wang, Andrew R. Pelletier, Mpho Letebele, Tlhomamo Pheto, Doreen Ramogola-Masire, Shenaaz El-Halabi
Journal: MMWR Morbidity and Mortality Weekly Report (2015)

What is already known on this topic? Human papillomavirus (HPV) infection is common and aggressive in persons infected with human immunodeficiency virus (HIV). With an HIV prevalence of 28% among females aged 15–49, cervical cancer is the leading cause of cancer death among women in Botswana. Before 2013, HPV vaccine had not been used in the public sector in Botswana.What is added by this report? Efforts to expand services for cervical cancer through the Pink Ribbon Red Ribbon initiative focused on HPV-related disease in Botswana. A demonstration project for HPV vaccination was developed by the Ministry of Health for school girls aged ≥9 years in primary schools in one community. A total of 1,967 (79%) of 2,488 eligible girls received 3 doses of vaccine in the immunization effort that was centered in schools.What are the implications for public health practice? Preventing HPV infection in girls is an important component of a national comprehensive cervical cancer control program. HPV vaccination programming is challenging, and demonstration projects can prepare countries for national introduction. The success of the initial HPV vaccination effort in Botswana led to an expanded project in 2014, with implementation of nationwide rollout of the HPV vaccine in 2015. It might be beneficial for future HPV vaccination campaigns to include strategies to reach out-of-school girls.