tbuckley/cabot-search huggingface dataset:
Retardation of Postsurgical Metastases With the Use of Extracted Tumor-Specific Transplantation Antigens and Cyclophosphamide&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN3"&gt;3&lt;/xref&gt;
Authors: S Nomi, N R Pellis, B D Kahan
Journal: JNCI Journal of the National Cancer Institute (1984)

In a 3-methylcholanthrene [(MCA) CAS: 56-49-5]-induced tumor model of C3H/HeJ mice excision of a growing primary tumor decreased concomitant immunity and facilitated experimental lung metastases. Administration of tumor-specific transplantation antigens extracted from viable MCA-F cells with the use of single-phase (2.5%) 1-butanol [crude butanol extract (CBE)] augmented immunity after resection of the primary MCA-F tumor. Two weeks after footpad inoculation of 2×105 MCA-F cells, the tumor-bearing limbs were amputated and the mice were challenged subsequently with 5×104 cells of clone-9-4, a metastatic variant of MCA-F, via the tail vein. Whereas treatment with either 50 µg CBE sc or 20 mg cyclophosphamide (CY)/kg ip failed to retard lung colonization, combination therapy with the two agents reduced the incidence of lung colonies by 69.8% (26.5 vs. 8; P<.001) compared with the incidence in the surgery-alone group and by 55.5% (18 vs. 8; P<.001) compared with the incidence in the group treated with surgery and CY. Furthermore, the combined effects of CBE and CY were immunologically specific: The combined therapy with the non-cross-reactive MCA-D-CBE did not protect against iv challenge with clone-9-4. Treatment with antigenic extracts induced a 21.4% (4.2 vs. 3.3%) decrease in the ratio of Lyt H:Lyt 2+ cells in the spleens of tumor-resected mice, which suggested restoration to normal levels. Therefore, in the combined regimen, antigen may induce specific activation of helper lymphocytes, while CY inhibits activation of suppressor cells.
Etanercept plus narrowband ultraviolet B phototherapy of psoriasis is more effective than etanercept monotherapy at 6 weeks
Authors: T. Gambichler, C. Tigges, N. Scola, J. Weber, M. Skrygan, F.G. Bechara, P. Altmeyer, A. Kreuter
Journal: British Journal of Dermatology (2011)

Background A substantial portion of patients with psoriasis does not achieve a satisfactory response under antitumour necrosis factor (TNF)‐α biological therapies. Objectives We aimed to evaluate whether etanercept plus narrowband ultraviolet B (NB‐UVB) phototherapy is superior to etanercept monotherapy in the management of psoriasis. Methods In this prospective study, patients with psoriasis were treated with etanercept 25 mg twice weekly. Two marker lesions were selected for determination of the modified Psoriasis Area and Severity Index (M‐PASI). NB‐UVB was administered thrice weekly whereby one marker lesion was covered as nonirradiated control. Skin biopsies for histology and immunohistochemistry were performed in both marker lesions after a 6‐week treatment course. Results After 6 weeks of therapy, the relative M‐PASI reduction (mean ± SD) in etanercept‐treated sites (53·7 ± 36·9%) was significantly lower than the reduction in etanercept plus NB‐UVB‐treated lesions (64 ± 27·8%; P =0·011). At the end of treatment, histology scores of etanercept‐treated psoriatic plaques were significantly higher than scores of etanercept plus NB‐UVB‐treated sites (4·6 ± 2·7 vs. 3·7 ± 2·4; P =0·045). Epidermal immunoreactivity for CD1a, CD4 and CD8 was significantly lower in etanercept plus NB‐UVB‐treated lesions when compared with etanercept monotherapy. Conclusions Etanercept combined with NB‐UVB is more effective than etanercept monotherapy at 6 weeks as demonstrated at a clinical, histological and immunohistological level. However, as there is an increased risk for malignancy by treatment with TNF‐α blockers alone or in combination with phototherapy, we recommend to restrict this highly effective combination to short periods of time, for instance to obtain a quicker response, and to avoid long‐term treatment.
MODIFICATION OF THE ELECTROFIT
Authors: DAVID J. IMPASTATO, ROBERT BAK, JOHN FROSCH, S. BERNARD WORTIS
Journal: American Journal of Psychiatry (1943)

1. Sodium amytal is effective in the management of the resistive and apprehensive patient, and the post convulsive excitement. It can be used to elicit prognostic productions. More patients can be treated during a given time period. 2. Our preliminary studies indicate that sodium amytal can lessen the severity of the ordinary convulsion or practically abolish it. 3. Our therapeutic results in a small group of patients are as good as those who have not received sodium amytal. 4. No fractures of the spine or other bones have been sustained by our patients. 5. Sodium amytal does not cause alarming apnea, nor does it have the other disadvantages of curare. 6. Our results warrant further use and investigation of the pre-convulsive intravenous use of sodium amytal.
SOD1 protein aggregates stimulate macropinocytosis in neurons to facilitate their propagation
Authors: Rafaa Zeineddine, Jay F. Pundavela, Lisa Corcoran, Elise M. Stewart, Dzung Do-Ha, Monique Bax, Gilles Guillemin, Kara L. Vine, Danny M. Hatters, Heath Ecroyd, Christopher M. Dobson, Bradley J. Turner, Lezanne Ooi, Mark R. Wilson, Neil R. Cashman, Justin J. Yerbury
Journal: Molecular Neurodegeneration (2015)

Amyotrophic Lateral Sclerosis is characterized by a focal onset of symptoms followed by a progressive spread of pathology that has been likened to transmission of infectious prions. Cell-to-cell transmission of SOD1 protein aggregates is dependent on fluid-phase endocytosis pathways, although the precise molecular mechanisms remain to be elucidated. We demonstrate in this paper that SOD1 aggregates interact with the cell surface triggering activation of Rac1 and subsequent membrane ruffling permitting aggregate uptake via stimulated macropinocytosis. In addition, other protein aggregates, including those associated with neurodegenerative diseases (TDP-43, Httex146Q, α-synuclein) also trigger membrane ruffling to gain entry into the cell. Aggregates are able to rupture unstructured macropinosomes to enter the cytosol allowing propagation of aggregation to proceed. Thus, we conclude that in addition to basic proteostasis mechanisms, pathways involved in the activation of macropinocytosis are key determinants in the spread of pathology in these misfolding diseases.
Histopathologic Prognostic Factors in Neuroblastic Tumors: Definition of Subtypes of Ganglioneuroblastoma and an Age-Linked Classification of Neuroblastomas
Authors: Hiroyuki Shimada, Jane Chatten, William A. Newton, Nancy Sachs, Ala B. Hamoudi, Tsuneo Chiba, Henry B. Marsden, Kazuaki Misugi
Journal: JNCI Journal of the National Cancer Institute (1984)

Histopathologic prognostic factors of 295 pretreatment tumors of a total 641 neuroblastomas and ganglioneuroblastomas were studied with the use of the following proposed tumor classification. The tumors were divided into 2 groups: stroma-poor (235 cases) and stroma-rich (60 cases) according to their organizational pattern (stromal development). The stroma-poor group was classified further into 2 subgroups: favorable stroma-poor (84% survival) and unfavorable stroma-poor (4.5% survival) according to the patient's age at diagnosis, degree of maturation, and nuclear pathology [mitosis-karyorrhexis index (MKI)] of the neuroblastic cells. The stroma-rich group was further classified into 3 subgroups: well differentiated (100% survival), intermixed (92% survival), and nodular (18% survival) on the basis of morphology of the immature element in the tumor tissue without regard to patient's age or quantitative maturation. Favorable stroma-poor and well-differentiated and intermixed stroma-rich groups seem to make good prognosis groups (87% survival), which show gradual progression along a maturational sequence according to the age of the patient. Unfavorable stroma-poor and nodular stroma-rich groups form poor prognosis groups (7% survival) and show morphological evidence of malignant or aggressive behavior, such as inappropriate immaturity for age, higher MKI, and gross nodule formation by immature neuroblasts.
Human Gastric Carcinoma: Prognosis in Relation to Macroscopic and Microscopic Features of the Primary Tumor
Authors: M Okada, S Kojima, M Murakami, T Fuchigami, T Yao, T Omae, A Iwashita
Journal: JNCI Journal of the National Cancer Institute (1983)

The correlation of prognosis with various clinical and pathologic factors was studied by use of multiple stepwise linear regression analysis among 77 patients undergoing resections for gastric cancer. Factors such as depth of penetration, invasion of the duodenum, macroscopic appearance, intramural and extramural growth pattern of the cancer, lymphatic or vascular invasion, and cancer cell-free dense submucosal fibrosis around the cancerous area were significant, and independent factors correlated with the prognosis, in that order. When these factors were taken into account, other factors such as sex and age of the patient, location, size, and histologic classification of the tumor, and folds' convergence were not significant.
Abstract IA27: Combination immunotherapy for melanoma
Authors: Jedd D. Wolchok
Journal: Cancer Research (2015)

Abstract The past decade has been a period of significant progress in the area of cancer immunotherapy enabled by significant advances in basic science allowing for a better understanding of molecular mechanisms of immune regulation and immune cell dynamics, stressing the importance of close collaboration between basic and translational and clinical scientists. Blockade of CTLA-4 was suggested to be an impactful means to augment tumor immunity based on the pioneering studies of Jim Allison, who hypothesized that impairment of this critical molecular brake would overcome tumor-induced immune suppression and allow for more robust immune response to tumors. In 2011, the US FDA approved ipilimumab for the treatment of metastatic melanoma with two randomized phase 3 trials demonstrating prolongation of overall survival, the first intervention ever to demonstrate this important endpoint in this challenging clinical situation. Investigation of blockade of the PD-1 (programmed death-1) pathway followed very shortly after the efficacy of ipilimumab was observed. PD-1 is a marker on T cells which, while being up-regulated after activation, serves to mark T cells as being exhausted and, when engaging one of its ligands (PD-L1 or -L2), can lower the threshold for apoptosis in T cells. An ever-expanding list of antibodies that block either PD-1 or PD-L1 has entered clinical trials with some currently in phase 3 investigation. It was therefore not completely surprising that PD-1 blockade showed clinical efficacy in melanoma. Given the activity noted with both CTLA-4 and PD-1 blockade and the complementary mechanism of action as well as supportive pre-clinical data, clinical trials are now investigating combination checkpoint blockade. The most mature data has come from a combination of ipilimumab + nivolumab in patients with melanoma and showed an overall response rate of 40% across dose cohorts with over 50% of patients in some cohorts showing rapid and deep (&amp;gt;80% reduction) tumor regressions in the context of manageable toxicity. Responses are generally rapidly apparent and durable. Two-year overall survival rates have been estimated at 79% across all cohorts. Phase 2 and 3 trials of this combination are ongoing. Citation Format: Jedd D. Wolchok. Combination immunotherapy for melanoma. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr IA27.
Effect of Laparoscopic-Assisted Resection vs Open Resection on Pathological Outcomes in Rectal Cancer
Authors: Andrew R. L. Stevenson, Michael J. Solomon, John W. Lumley, Peter Hewett, Andrew D. Clouston, Val J. Gebski, Lucy Davies, Kate Wilson, Wendy Hague, John Simes
Journal: JAMA (2015)

<h3>Importance</h3> Laparoscopic procedures are generally thought to have better outcomes than open procedures. Because of anatomical constraints, laparoscopic rectal resection may not be better because of limitations in performing an adequate cancer resection. <h3>Objective</h3> To determine whether laparoscopic resection is noninferior to open rectal cancer resection for adequacy of cancer clearance. <h3>Design, Setting, and Participants</h3> Randomized, noninferiority, phase 3 trial (Australasian Laparoscopic Cancer of the Rectum; ALaCaRT) conducted between March 2010 and November 2014. Twenty-six accredited surgeons from 24 sites in Australia and New Zealand randomized 475 patients with T1-T3 rectal adenocarcinoma less than 15 cm from the anal verge. <h3>Interventions</h3> Open laparotomy and rectal resection (n = 237) or laparoscopic rectal resection (n = 238). <h3>Main Outcomes and Measures</h3> The primary end point was a composite of oncological factors indicating an adequate surgical resection, with a noninferiority boundary of Δ = −8%. Successful resection was defined as meeting all the following criteria: (1) complete total mesorectal excision, (2) a clear circumferential margin (≥1 mm), and (3) a clear distal resection margin (≥1 mm). Pathologists used standardized reporting and were blinded to the method of surgery. <h3>Results</h3> A successful resection was achieved in 194 patients (82%) in the laparoscopic surgery group and 208 patients (89%) in the open surgery group (risk difference of −7.0% [95% CI, −12.4% to ∞];<i>P</i> = .38 for noninferiority). The circumferential resection margin was clear in 222 patients (93%) in the laparoscopic surgery group and in 228 patients (97%) in the open surgery group (risk difference of −3.7% [95% CI, −7.6% to 0.1%];<i>P</i> = .06), the distal margin was clear in 236 patients (99%) in the laparoscopic surgery group and in 234 patients (99%) in the open surgery group (risk difference of −0.4% [95% CI, −1.8% to 1.0%];<i>P</i> = .67), and total mesorectal excision was complete in 206 patients (87%) in the laparoscopic surgery group and 216 patients (92%) in the open surgery group (risk difference of −5.4% [95% CI, −10.9% to 0.2%];<i>P</i> = .06). The conversion rate from laparoscopic to open surgery was 9%. <h3>Conclusions and Relevance</h3> Among patients with T1-T3 rectal tumors, noninferiority of laparoscopic surgery compared with open surgery for successful resection was not established. Although the overall quality of surgery was high, these findings do not provide sufficient evidence for the routine use of laparoscopic surgery. Longer follow-up of recurrence and survival is currently being acquired. <h3>Trial Registration</h3> anzctr.org Identifier:ACTRN12609000663257
Physiologic Basis of Respiratory Disease
Authors: P. J. Sterk
Journal: European Respiratory Journal (2006)

Physiologic Basis of Respiratory Disease    Edited by Q. Hamid, J. Shannon and J. Martin    Published by BC Decker Inc., Hamilton, Ontario, Canada    Pages: 793. Price: £95, \#8364;140. ISBN: 1-55009-236-7    

This book is very timely and fills the wide gap between respiratory cell biology and clinical medicine. Since the 1990s there have been eye-catching advancements in the molecular as well as the clinical science of respiratory diseases. However, these two developments have largely occurred independently, as scientists at both ends encounter growing difficulties in understanding each other’s languages. This has certainly impeded the development of novel diagnostic and therapeutic strategies. Recently, it …
Racism in medicine
Authors: B R Pal, P. Singh, P. McDonald, N. Dogra, N. Karnik, C. Essex, J V R Barbour, R. Bhopal
Journal: BMJ (2001)

Editor—I applaud Bhopal for writing the truth about what each one of us has to face, personally and professionally during service in the NHS.1 It is time we all recognised that covert and overt racist practices occur within the NHS, and there needs to be an immediate arbitration panel in each region that can resolve issues speedily and hear both sides of disputes independently.
Video-assisted thoracoscopic surgery of mediastinal cysts: Report of 13 cases
Authors: Yener Aydin, Omer Araz, Mesut Ozgokce, Ilker Ince, Fatih Alper, Atilla Eroglu
Journal: European Respiratory Journal (2012)

Background : Mediastinal cysts are rare anomalies. The purpose of this study was to present our experience with mediastinal cysts who were thoracoscopic treated in our clinic and to discuss our findings along with those from the literature.   Methods:  We retrospectively investigated 13 patients who were diagnosed and thoracoscopic treated for mediastinal cysts in our clinic between January 2008 and December 2011.   Results:  Seven patients were female and six patients were male. The average age of the patients was 41.3 ± 20.3 (7-82 years old). The mediastinal cysts comprised five pericardial cysts; four bronchogenic cysts; one hydatid cyst; one benign cystic teratoma; one thymic cyst; and one neurenteric cyst. In a case with ruptured hydatid cyst, we passed to thoracotomy intra-operatively due to presence of advanced adhesion related to inflammation. Postoperative complication and mortality did not occur in any case. The average postoperative hospitalization period was 3.8 days (2-7 days).   Conclusion:  Video-assisted thoracoscopic surgery in mediastinal cysts is a reliable and effective approach with low morbidity and a shorter hospital stay.   Keywords:  Mediastinal cyst, VATS.
Phase II study of vinorelbine in patients with androgen-independent prostate cancer
Authors: S. Oudard, A. Caty, Y. Humblet, M. Beauduin, E. Sue, M. Piccart, F. Rolland, P. Fumoleau, R. Bugat, P. Houyau, A. Monnier, X. Sun, P. Montcuquet, J. Breza, J. Novak, T. Gil, D. Chopin
Journal: Annals of Oncology (2001)
Improving the cancer chemotherapy use process.
Authors: D S Fischer, S Alfano, M T Knobf, C Donovan, N Beaulieu
Journal: Journal of Clinical Oncology (1996)

PURPOSE Reports of the tragic consequences of erroneous cancer chemotherapy overdoses at a prominent cancer center and a university hospital prompted a review of our institution's practices and those of 123 other hospitals to ascertain for each the current in-house process to prevent chemotherapy errors. METHODS A multidisciplinary committee of oncologists, nurses, and pharmacists reviewed the chemotherapy use process and identified opportunities for improvement. A 1-page facsimile survey was answered by 150 of 215 members of the American Society of Clinical Oncology (ASCO) who received it. RESULTS We further restricted the writing of cytotoxic chemotherapy orders to physicians who were board-certified or -eligible in hematology or medical, pediatric, and gynecologic oncology and their approved fellows. Dispensation of drugs is limited to oncology-certified pharmacists, and administration to chemotherapy-certified nurses. Standard orders are used either on special oncology forms or designated order sets in the computer. Procedures to regulate the ordering of antineoplastic drugs for nonmalignant indications by nononcology specialists are outlined. A process to prevent chemotherapy errors is in place in 95% of hospitals. Dedicated medical oncology units are ubiquitous, and most cancer centers and university hospitals have dedicated gynecologic and pediatric oncology units. Chemotherapy orders are generally written by oncology fellows and countersigned by an attending oncologist in cancer centers and university hospitals, whereas private oncology attending physicians write them in most community hospitals. Drugs are administered by oncology-certified nurses in most institutions. CONCLUSIONS These recommendations should improve the safety and effective use of chemotherapy and reduce the error rate to as close to zero as human fallibility will allow.
Abstract 13469: Alpha1-AMPK Deletion Enhances Endothelial Dysfunction and Vascular Oxidative Stress During Chronic Angiotensin II Treatment by Upregulation of Nox2
Authors: Swenja Schuhmacher, Marc Foretz, Maike Knorr, Marcus Hortmann, Philip Wenzel, Matthias Oelze, Andreas Daiber, Thomas Munzel, Benoit Viollet, Eberhard Schulz
Journal: Circulation (2010)

Background: AMP-activated protein kinase (AMPK) plays a pivotal role in cellular adaptation to decreased energy supply. In the vasculature, AMPK activates endothelial NO synthase, promotes angiogen...
Margaret McCartney: The “breakthrough” drug that’s not been shown to help in Alzheimer’s disease
Authors: Margaret McCartney
Journal: BMJ (2015)

Our airwaves have been saturated, and the column inches heaved with the news: there's been a breakthrough."Landmark drug to stop Alzheimer's disease has been unveiled . . .Solanezumab has been shown to slow or even halt the illness," sang the Daily Mail. 1 A "very excited" Eric Karran, from the charity Alzheimer's Research UK, told the BBC that "these findings are hugely significant in that it's the first data that we've had with the drug actually slowing down the course of the disease . . .we could be on the verge of a . . .radical breakthrough for people with Alzheimer's disease."
Multiple Myeloma Cells Express Functional E-Selectin Ligands Which Can be Inhibited Both in-Vitro and in-Vivo Leading to Prolongation of Survival in a Murine Transplant Model
Authors: Alessandro Natoni, Michele Moschetta, Siobhan Glavey, Ping Wu, Gareth J. Morgan, Lokesh Joshi, John L. Magnani, Irene M. Ghobrial, Michael E O'Dwyer
Journal: Blood (2014)
Nonpharmacological interventions for insomnia: a meta-analysis of treatment efficacy
Authors: C M Morin, J P Culbert, S M Schwartz
Journal: American Journal of Psychiatry (1994)

Because of the role of psychological factors in insomnia, the shortcomings of hypnotic medications, and patients' greater acceptance of nonpharmacological treatments for insomnia, the authors conducted a meta-analysis to examine the efficacy and durability of psychological treatments for the clinical management of chronic insomnia.A total of 59 treatment outcome studies, involving 2,102 patients, were selected for review on the basis of the following criteria: 1) the primary target problem was sleep-onset, maintenance, or mixed insomnia, 2) the treatment was nonpharmacological, 3) the study used a group design, and 4) the outcome measures included sleep-onset latency, time awake after sleep onset, number of nighttime awakenings, or total sleep time.Psychological interventions, averaging 5.0 hours of therapy time, produced reliable changes in two of the four sleep measures examined. The average effect sizes (i.e., z scores) were 0.88 for sleep latency and 0.65 for time awake after sleep onset. These results indicate that patients with insomnia were better off after treatment than 81% and 74% of untreated control subjects in terms of sleep induction and sleep maintenance, respectively. Stimulus control and sleep restriction were the most effective single therapy procedures, whereas sleep hygiene education was not effective when used alone. Clinical improvements seen at treatment completion were well maintained at follow-ups averaging 6 months in duration.The findings indicate that nonpharmacological interventions produce reliable and durable changes in the sleep patterns of patients with chronic insomnia.