tbuckley/cabot-search huggingface dataset:
Extended analyses: Combined androgen blockade (CAB) therapy with bicalutamide vs. luteinizing hormone-releasing hormone agonist (LHRHa) monotherapy in Japanese men with untreated advanced prostate cancer
Authors: H. Akaza, S. Hinotsu, M. Usami, Y. Arai, H. Kanetake, S. Naito, Y. Hirao
Journal: Journal of Clinical Oncology (2008)

5063 Background: Phase III trial (PIII) results of first-line CAB (bicalutamide 80 mg [licensed dose in Japan] plus LHRHa) for Japanese men with advanced prostate cancer (PC) were shown to be significantly better than LHRHa monotherapy in TTP and TTTF without reduced tolerability, and achieve earlier QOL improvement. This report was cited in the 2007 Update of ASCO Practice Guideline Recommendations. PSA was also decreased significantly faster and lower with CAB than LHRHa alone. The PIII showed no difference in overall survival (OS) between the groups because of lack of events, but a long-term follow-up of PIII conducted by CABPC Study did indicate a significant OS benefit for CAB over LHRHa alone. Here we present the final analyses of this long-term follow-up study. Methods: Five-year survival rates for 203 Japanese men with advanced PC in the original study (CAB=102, LHRHa alone=101) were calculated (Kaplan- Meier method), and OS, cause-specific survival (CSS) and OS by PSA nadir were analyzed by use of Cox regression (HR) and log-rank test. Results: Both groups were demographically similar. At the 270 weeks median follow-up, there were 26 deaths in the CAB and 38 in the LHRHa alone. OS for the CAB group was significantly better than for LHRHa alone p=0.0425. Five-year survival rates for CAB and LHRHa alone were 75.3% and 63.4% respectively. CSS was higher with CAB, but the difference was not statistically significant. OS by PSA nadir ≤1 ng/mL was significantly better than for those >1 ng/mL (p<0.0001). Conclusions: For Japanese men with advanced PC, long-term follow-up data had shown a significant OS benefit for CAB with bicalutamide compared with LHRHa monotherapy; and exploratory data suggesting that lowering PSA may be prognostic for OS. In this study, antiandrogens were added to most men with disease progression in the LHRHa alone (response rate 78%, median duration of response 40wks); most with progression in the CAB were observed for AWS (AWS rate 39%, median duration of AWS 58wks). So this result suggests that immediate CAB prolongs survival better than deferred CAB. No significant financial relationships to disclose.
The role of venography in the evaluation of malfunctioning central venous access ports (CVAPs)
Authors: E. Atallah, M. Salomon, C. A. Schiffer, B. El-Rayes
Journal: Journal of Clinical Oncology (2006)

18535 Background: Malfunction of CVAPs is common in cancer patients receiving chemotherapy. We evaluated the role of venography as a means of assessing the cause of malfunction. Methods: We reviewed and analyzed data available from cancer patients who had a venogram for a malfunctioning CVAP between 1/03 to 3/05. All patients in our institution who have a malfunctioning CVAP receive a trial of intracatheter thrombolytics. If the malfunction persists, then a venogram is performed through the catheter. Results: Seventy-seven patients were studied. The indication for evaluation was inability to aspirate blood (54%), pain (18%), swelling at site of injection (10%), difficult aspiration and infusion (6.5%) and others (11.5%). Forty-four patients had chest ports (31% left and 26% right side), while 33 patients had the CVAP placed in the upper extremity (24% right and 18% left arm). Fibrin sheath or thrombus was the most common finding in 44% of patients, and 41% of venograms were normal. Only two patients had soft tissue extravasation of contrast. Sites of extravasation were in the chest at the catheter/port junction and in the supraclavicular area secondary to a catheter fracture. In patients with aspiration failure, 68% had either a fibrin sheath or thrombus at the catheter tip, 14% had CVAP malposition as the only abnormality, 14% were normal and one patient had extravasation. The CVAP tips were optimally positioned in 70% of patients (distal superior vena cava (SVC), venocava-atrial junction or atrium), while 30% were in a suboptimal position (proximal SVC, brachiocephalic, azygous, or internal jugular vein). Suboptimally positioned CVAPs had a higher incidence of an associated abnormality compared to optimally positioned CVAPs (58% vs. 4% P = 0.001). Only five CVAPs were removed, for extravasation (1), cellulitis (2), and malposition (2). Conclusion: Although the incidence of extravasation was low, venography evaluation could be considered in patients with malfunctioning catheters receiving a vesicant drug to help prevent a potentially significant complication. CVAPs with suboptimally positioned tips had a higher rate of associated abnormalities, emphasizing the importance of proper tip position. No significant financial relationships to disclose.
The why of fragging
Authors: T C Bond
Journal: American Journal of Psychiatry (1976)

The author studied 28 men convicted and confined for use of explosives in assaults on superior officers during the Viet Nam war. There were several predominant characteristics in this group, including deprivation and/or brutality in family backgrounds, poor self-image, lack of critical self-observation, the use of externalization, and feelings of insecurity or vulnerability. Drug use joined with these and several other factors related to the situation of these men in Viet Nam in a lethal combination that led to the perpetration of an indirect assault with an explosive device on a figure perceived as powerful and threatening.
Guideline discordance in the use of radiographic imaging during initial workup of patients with prostate cancer (CaP).
Authors: Aaron David Falchook, Laura H. Hendrix, Ronald C. Chen
Journal: Journal of Clinical Oncology (2013)

109 Background: Overuse of imaging in patients unlikely to have metastatic disease is costly and can lead to patient harm from unnecessary procedures. However, underuse of imaging leads to undiagnosed metastatic disease, resulting in aggressive treatments in incurable patients. The National Comprehensive Cancer Network (NCCN) recommends bone scans and computed tomography (CT) or magnetic resonance imaging (MRI) during initial work-up of select patients with intermediate or high risk CaP. We quantify the proportion of patients who received work-up discordant with NCCN guidelines. Methods: Patients in the Surveillance Epidemiology and End Results (SEER)-Medicare database diagnosed from 2004-2007 were included. We report bone scan and CT/MRI from date of diagnosis to the earlier of treatment or 6 months. Results: 65% of patients for whom bone scan is recommended received it, and 49% received recommended CT/MRI. Further, 43% of patients for whom bone scan is not recommended received it, and 38% received unnecessary CT/MRI. Age and race were significantly associated with discordance on multivariate models (Table). Underuse of recommended bone and CT/MRI scans decreased in more recent years, but overuse of unnecessary CT/MRI increased. There was significant regional variation. Conclusions: There is a high prevalence of both overuse and underuse of guideline-recommended imaging in CaP. [Table: see text]
Pilot trial assessing the feasibility of intra-ductal delivery of epirubicin (epi)-containing nanoparticles (NP) via InDuct<sup>@</sup> Breast Microcatheter (IDBM)
Authors: R. J. Goulet, S. Badve, L. Brannon-Peppas, D. Rouch, C. Huntley, A. M. Storniolo
Journal: Journal of Clinical Oncology (2004)

828 Background: Over 95% of breast cancers (BC) originate in the epithelial cells lining the breast duct. We piloted the use of the IDBM as a targeted drug delivery tool to infuse epi-containing NP into the breast duct. Methods: Epi, a naturally fluorescent anthracycline, was encapsulated into biodegradable NP (diameter < 1μ), which could then be suspended in saline for injection. Informed consent was obtained from women with planned mastectomies. In the operating room, the mastectomy was performed and the tumor specimen was removed for pathologic assessment. Via the IDBM, 3–5 ml of NP (200 mg/ml suspended in saline), containing 6% epi, were injected into a breast duct that had been previously marked with vital blue dye. The duct was dissected, frozen intact, and subsequently “step-sectioned”. Sections were examined by fluorescent microscopy to assess presence of intact NP within the ductal lumen. “Success” was defined as the presence of intact NP within the lumen of the distal one-third of the dissected duct. Results: Nineteen women signed informed consent prior to their mastectomies. Thirteen duct dissections were frozen and examined. Of these 13, intact NP were seen in the terminal lobules in 8 specimens. Of the remaining 5 specimens, the duct wall had been perforated (1) and the NP clumped in the syringe (1). No explanations were provided for the remaining 3 NP-free specimens. In 6 patients, the cannulations were unsuccessful because of history of prior areolar surgery (2); history of prior breast irradiation (1); specimen inadvertently fixed in formalin (1); schedule mishap (1); and no reason provided (1). Conclusion: This pilot study demonstrated that it is feasible to use the IDBM to cannulate the breast ducts and infuse a substance throughout a specific ductal network, all the way to the terminal lobules. In vivo Phase I trials using this technique are being planned. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biogel Technology, Inc. Cytyc Corp.
Loss of Heterozygosity and Microsatellite Instability at theMLL Locus Are Common in Childhood Acute Leukemia, but not in Infant Acute Leukemia
Authors: Julie C. Webb, Irina Golovleva, Alan H. Simpkins, Helena Kempski, Brian Reeves, Natalie Sturt, Judith M. Chessells, Paul M. Brickell
Journal: Blood (1999)
Abstract 1635: Mesenchymal Stem Cell Therapy Prevents Ischemia/Reperfusion Injury
Authors: E Manning, S Pham, S Li, R Vazquez-Padron, J Mathew, P Ruiz, S Salgar
Journal: Circulation (2008)

Ischemic heart disease, especially myocardial infarction, is an important cause for heart failure. However, therapeutic potential of mesenchymal stem cells (MSC) for myocardial or pulmonary ischemia/reperfusion (IR) injury is not well studied. MSC were tested for their ability to prevent warm IR injury.   Methods:  Bone marrow cells from Lewis rat were cultured in plastic tissue culture flasks for 72 hours; cells in suspension were discarded and the adherent cells (MSC) were expanded. Experimental design: following 120 minutes of left lung ischemia, Group A, rats received MSC (~2 x 10 6 ; i.v.; passage 2– 6); Group B, rats received fibroblasts (~2 x 10 6 ; i.v.) ; Group C, received saline; and Group D received no ischemia or MSC. Left lung ischemia was performed by clamping left pulmonary artery/vein/bronchus at end inspiration. At 4h, 24h and 72h following ischemia, blood was collected from left and right pulmonary veins, separately.   Results : Mean blood oxygenation (PaO2/FIO2 ratio, mmHg) at 24h was significantly (P  Ex vivo  expanded MSC (passage 2) were highly positive for stem cell markers CD29, CD90, and CD44 (70–95%) and weakly positive for CD31, CD45 and CD11b (6 –24%).   Conclusions:  Autologous MSC therapy to prevent IR injury and improve lung function in cardiopulmonary diseases seems promising.
Computer Vision Tool and Technician as First Reader of Lung Cancer Screening CT Scans
Authors: Alexander J. Ritchie, Calvin Sanghera, Colin Jacobs, Wei Zhang, John Mayo, Heidi Schmidt, Michel Gingras, Sergio Pasian, Lori Stewart, Scott Tsai, Daria Manos, Jean M. Seely, Paul Burrowes, Rick Bhatia, Sukhinder Atkar-Khattra, Bram van Ginneken, Martin Tammemagi, Ming Sound Tsao, Stephen Lam
Journal: Journal of Thoracic Oncology (2016)
Perturbed Mucosal Immunity and Dysbiosis Accompany Clinical Disease in a Rat Model of Spondyloarthritis
Authors: Mark J. Asquith, Patrick Stauffer, Sean Davin, Claire Mitchell, Phoebe Lin, James T. Rosenbaum
Journal: Arthritis & Rheumatology (2016)

The HLA-B27/β2 -microglobulin (β2 m)-transgenic (Tg) rat is a leading model of B27-associated spondyloarthritis (SpA), and the disease is dependent on the presence of intestinal bacteria. Previous studies have shown that adult HLA-B27/β2 m-Tg rats have an altered intestinal microbiota. This study sought to better define the age-dependent changes to both mucosal immune function and dysbiosis in this rat model of SpA.Intestinal contents were collected from wild-type and HLA-B27/β2 m-Tg rats postweaning (ages 3 and 6 weeks), at disease onset (age 10 weeks), and after the establishment of disease (ages ≥16 weeks). The microbial community structure was determined by 16S ribosomal RNA sequencing and quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Mucosal and systemic Th1, Th17, and Treg cell responses were analyzed by flow cytometry, as was the frequency of IgA-coated intestinal bacteria. Intestinal expression of inflammatory cytokines and antimicrobial peptides (AMPs) was determined by qRT-PCR.An inflammatory cytokine signature and elevated AMP expression during the postweaning period preceded the development of clinical bowel inflammation and dysbiosis in HLA-B27/β2 m-Tg rats. An early and sustained expansion of the Th17 cell pool was specifically observed in the cecal and colonic mucosa of HLA-B27/β2 m-Tg rats. Strongly elevated intestinal colonization of Akkermansia muciniphila and an increased frequency of IgA-coated fecal bacteria were significantly associated with expression of HLA-B27 and arthritis development.HLA-B27/β2 m expression in this rat model renders the host hyperresponsive to microbial antigens from infancy. Early activation of innate immunity and expansion of a mucosal Th17 signature are soon followed by dysbiosis in HLA-B27/β2 m-Tg animals. The pathologic processes of perturbed mucosal immunity and dysbiosis strongly merit further study in both prediseased and diseased populations of patients with SpA.
Gamma-Glutamyl Transpeptidase: A Positive Marker for Cultured Rat Liver Cells Derived From Putative Premalignant and Malignant Lesions2
Authors: Brian A. Laishes, Katsuhiro Ogawa, Esther Roberts, Emmanuel Farber
Journal: JNCI Journal of the National Cancer Institute (1978)

Journal Article Gamma-Glutamyl Transpeptidase: A Positive Marker for Cultured Rat Liver Cells Derived From Putative Premalignant and Malignant Lesions Get access Brian A. Laishes, Brian A. Laishes 4 4Address reprint requests to Dr. Laishes at his present address: McArdle Laboratory for Cancer Research, University of Wisconsin, Madison, Wis.53706. Search for other works by this author on: Oxford Academic PubMed Google Scholar Katsuhiro Ogawa, Katsuhiro Ogawa Search for other works by this author on: Oxford Academic PubMed Google Scholar Esther Roberts, Esther Roberts Search for other works by this author on: Oxford Academic PubMed Google Scholar Emmanuel Farber Emmanuel Farber Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 60, Issue 5, May 1978, Pages 1009–1016, https://doi.org/10.1093/jnci/60.5.1009 Published: 01 May 1978 Article history Received: 13 June 1977 Accepted: 02 November 1977 Published: 01 May 1978
PWE-319 The relationship with body composition of ccr7-positive cells in colorectal cancer
Authors: G Malietzis, GH Lee, D Bernardo, S Knight, M Moorghen, HO Al-Hassi, JT Jenkins
Journal: Gut (2015)

<h3>Introduction</h3> Emerging data support the link between systemic inflammatory response (IR) and body composition alterations in cancer patients but limited information exists on how the local IR to the tumour is associated to these changes. Regulation of the local IR is largely achieved through chemokine synthesis from the tumour microenvironment such as C-Chemokine-Receptor-7 (CCR7). In the present study, we determined the expression of CCR7 in primary colorectal cancer (CRC) and also correlated the expression of CCR7 with the patients’ clinical and pathological parameters (including their body composition derived from computerised tomography (CT) analysis) to explore the relationship between body composition and tumour immunology in CRC. <h3>Method</h3> A study of paraffin-embedded tissue specimens was carried out in 116 patients with non-metastatic CRC. CCR7 expression was determined by immunohistochemistry. Analysis of computer tomography scans was used to calculate BC parameters. The relationship between CCR7 expression and other clinicopathological parameters was assessed using nonparametric statistics. <h3>Results</h3> The median tumour infiltrating CCR7+ cell density was 15.85% (Inter Quartile Range (IQR) 10.02–21.83%) in the tumour stroma, and 7.17% (IQR 3.90–12.37%) at the tumour margin. CCR7+ cell density of the two areas correlated positively (Spearman r = 0.77; p &lt; 00.001). We divided the cases into high and low CCR7+ groups according to the median value of CCR7 + cell density. High CCR7+ cell density at both the tumour centre and the margin was significantly associated with older age, higher tumour stage, lymph node metastasis and the presence of myosteatosis. High CCR7+ cell density at the tumour margin was also significantly associated with female sex and the presence of lymphovascular invasion. There was no significant association between CCR7+ cell density either at the margin or within an intra-tumoural location with BMI, site of tumour, grade of differentiation, myopenia or visceral adiposity. <h3>Conclusion</h3> We found that a high density of tumour-infiltrating CCR7+ cells was significantly associated with age, histological invasion, higher tumour stage, lymph node metastasis and myosteatosis that are adverse prognostic factors in CRC. These findings may therefore suggest a model whereby the stimulus for the local immune cell response is not only induced by the tumour but also influenced by host-related factors. We have now identified that myosteatosis is also related to an adverse local inflammatory response as measured by a high CCR7 density. To our knowledge these findings are novel and may support the hypothesis that host LIR may influence the development and persistence of myosteatosis. <h3>Disclosure of interest</h3> None Declared.
Diamond‐Nanoneedle‐Array‐Facilitated Intracellular Delivery and the Potential Influence on Cell Physiology
Authors: Xiaoyue Zhu, Muk Fung Yuen, Li Yan, Zhenyu Zhang, Fujin Ai, Yang Yang, Peter K. N. Yu, Guangyu Zhu, Wenjun Zhang, Xianfeng Chen
Journal: Advanced Healthcare Materials (2016)

Vertical arrays of nanostructures can provide access to the cell cytoplasma and probe intracellular molecules. Here, the simple combination of diamond nanoneedle arrays with centrifugation‐induced supergravity is shown to efficiently deliver drugs and biomaterials into the cytosol within several minutes, negotiating the endocytososomal system. The potential influence of the technique on cell metabolism is thoroughly studied. By detecting the phosphorylated histone variant H2AX (pH2AX) in the nucleus, it is proved that the operating process will not lead to DNA double‐strand breaks. However, the mechanical disruption can temporarily improve the permeability of the cell membranes. Nanoneedle treatment affects cell metabolism at multiple points. The treatment can slightly elevate the apoptotic signal in A549 cells and can significantly increase the production of reactive oxygen species (ROS) in cells, particularly if combined with anticancer drugs. Meanwhile, the activity of cytosolic glucose 6‐phosphate dehydrogenase (G6PD) is also raised to counterbalance the elevated ROS content. A detected depolarization of the mitochondrial membrane potential suggests mitochondrial involvement in the intracellular redox reactions and cell apoptosis which are induced by diamond nanoneedle treatment. Overall this study provides a novel understanding on the intracellular delivery mediated by nanoneedles, especially the impact on cell physiology.
Isorhapontigenin suppresses growth of patient-derived glioblastoma spheres through regulating miR-145/SOX2/cyclin D1 axis
Authors: Zhou Xu, Xingruo Zeng, Jiawei Xu, Derek Xu, Jingxia Li, Honglei Jin, Guosong Jiang, Xiaosi Han, Chuanshu Huang
Journal: Neuro-Oncology (2015)

Glioblastoma (GBM) is the most common malignant brain tumor, and glioma stem cells (GSCs) are considered a major source of treatment resistance for glioblastoma. Identifying new compounds that inhibit the growth of GSCs and understanding their underlying molecular mechanisms are therefore important for developing novel therapy for GBM. We investigated the potential inhibitory effect of isorhapontigenin (ISO), an anticancer compound identified in our recent investigations, on anchorage-independent growth of patient-derived glioblastoma spheres (PDGS) and its mechanism of action. ISO treatment resulted in significant anchorage-independent growth inhibition, accompanied with cell cycle G0-G1 arrest and cyclin D1 protein downregulation in PDGS. Further studies established that cyclin D1 was downregulated by ISO at transcription levels in a SOX2-dependent manner. In addition, ISO attenuated SOX2 expression by specific induction of miR-145, which in turn suppressed 3′UTR activity of SOX2 mRNA without affecting its mRNA stability. Moreover, ectopic expression of exogenous SOX2 rendered D456 cells resistant to induction of cell cycle G0-G1 arrest and anchorage-independent growth inhibition upon ISO treatment, whereas inhibition of miR-145 resulted in D456 cells resistant to ISO inhibition of SOX2 and cyclin D1 expression. In addition, overexpression of miR-145 mimicked ISO treatment in D456 cells. ISO induces miR-145 expression, which binds to the SOX2 mRNA 3′UTR region and inhibits SOX2 protein translation. Inhibition of SOX2 leads to cyclin D1 downregulation and PDGS anchorage-independent growth inhibition. The elucidation of the miR-145/SOX2/cyclin D1 axis in PDGS provides a significant insight into understanding the anti-GBM effect of ISO compound.
PROs in the Balance: Ethical Implications of Collecting Patient Reported Outcome Measures in the Electronic Health Record
Authors: Joshua S. Crites, Cynthia Chuang, Anne Dimmock, Wenke Hwang, Bobbie Johannes, Anuradha Paranjape, Albert W. Wu
Journal: The American Journal of Bioethics (2016)

"PROs in the Balance: Ethical Implications of Collecting Patient Reported Outcome Measures in the Electronic Health Record." The American Journal of Bioethics, 16(4), pp. 67–68
Peroral endoscopic myotomy using the posterior approach in an 11-month-old girl with achalasia, severe malnutrition, and recurrent pneumonia
Authors: Xiao-Cen Zhang, Quan-Lin Li, Ying Huang, Shi-Jian Miao, Ping-Hong Zhou
Journal: Endoscopy (2015)

Peroral endoscopic myotomy (POEM) has become widely accepted as a minimally invasive procedure for treatment of achalasia. Here we report a case of achalasia in an 11-month-old girl that was managed by POEM.
Can women themselves assess the outcome of an early medical abortion as safely and effectively as a clinic follow-up visit? : A randomised controlled, non-inferiority trial in India
Authors: Kirti Iyengar, Mandira Paul, Sharad Iyengar, Marie Klingberg-Allvin, Birgitta Essen, Johan Bring, Kristina Gemzell-Danielsson
Journal: The Lancet Global Health (2015)