tbuckley/cabot-search huggingface dataset:
Chemotherapy Acts as an Adjuvant to Convert the Tumor Microenvironment into a Highly Permissive State for Vaccination-Induced Antitumor Immunity
Authors: Tae Heung Kang, Chih-Ping Mao, Sung Yong Lee, Alexander Chen, Ji-Hyun Lee, Tae Woo Kim, Ronald D. Alvarez, Richard B.S. Roden, Drew Pardoll, Chien-Fu Hung, T.-C. Wu
Journal: Cancer Research (2013)

Multiple classes of pharmacologic agents have the potential to induce the expression and release of proinflammatory factors from dying tumor cells. As a result, these cells can in theory elicit an immune response through various defined mechanisms to permanently eradicate disseminated cancer. However, the impact of chemotherapy on the tumor-specific immune response in the context of the tumor microenvironment is largely unknown. Within the tumor microenvironment, the immune response promoted by chemotherapy is antagonized by an immune-suppressive milieu, and the balance of these opposing forces dictates the clinical course of disease. Here, we report that high antigen exposure within the tumor microenvironment following chemotherapy is sufficient to skew this balance in favor of a productive immune response. In elevating antigen exposure, chemotherapy can achieve long-term control of tumor progression without the need of an additional adjuvant. We found that chemotherapy initiated this phenomenon in the tumor microenvironment through an accumulation of dendritic cells, which stimulated CD8(+) T cells and the type I IFN pathway. From this conceptual base, we developed a simple approach to cancer therapy combining chemotherapy and vaccination that may be widely applicable.
Antigen-specific expansion and differentiation of natural killer cells by alloantigen stimulation
Authors: Tsukasa Nabekura, Lewis L. Lanier
Journal: The Journal of Experimental Medicine (2014)

Natural killer (NK) cells provide important host defense against microbial pathogens and can generate a population of long-lived memory NK cells after infection or immunization. Here, we addressed whether NK cells can expand and differentiate after alloantigen stimulation, which may be important in hematopoietic stem cell and solid tissue transplantation. A subset of NK cell in C57BL/6 mice expresses the activating Ly49D receptor that is specific for H-2Dd. These Ly49D+ NK cells can preferentially expand and differentiate when challenged with allogeneic H-2Dd cells in the context of an inflammatory environment. H-2Dd is also recognized by the inhibitory Ly49A receptor, which, when coexpressed on Ly49D+ NK cells, suppresses the expansion of Ly49D+ NK cells. Specificity of the secondary response of alloantigen-primed NK cells was defined by the expression of activating Ly49 receptors and regulated by the inhibitory receptors for MHC class I. Thus, the summation of signals through a repertoire of Ly49 receptors controls the adaptive immune features of NK cells responding to allogeneic cells.
Fcγ Receptor Polymorphisms as Biomarkers for Epidermal Growth Factor Receptor Antibodies
Authors: Thomas Valerius
Journal: Journal of Clinical Oncology (2010)

With great interest I read the editorial by Shepherd and Tsao 1 on epidermal growth factor receptor (EGFR) biomarkers in non-small-cell lung cancer (NSCLC).In this article, the authors comment on the biomarker analyses of the BMS099 trial, which appear in the same issue of Journal of Clinical Oncology, 2 and similar results from the First-Line Erbitux in Lung Cancer (FLEX) study, which have only been published in abstract form so far. 3 Interestingly, validated biomarkers for EGFR-directed tyrosine kinase inhibitors in NSCLC, such as EGFR or KRAS mutations, were not predictive for responses to EGFR antibodies, suggesting fundamental differences in the therapeutic modes of action between these two classes of EGFR inhibitors.In contrast to tyrosine kinase inhibitors, EGFR antibodies, including the immunoglobulin G2 antibody panitumumab, 4 recruit effector cells for antibody-dependent cellular cytotoxicity (ADCC).In vitro, in vivo, and clinical data, demonstrating an association between functional Fc␥ receptor polymorphisms and response to antibody therapy, have suggested ADCC as a major effector mechanism of other therapeutic antibodies. 5For cetuximab, two studies reported correlations between Fc␥ receptor polymorphisms and clinical responses in colorectal cancer, suggesting that blockade of signaling is not the only mechanism of action of cetuximab in vivo. 6,7Pending data on the impact of these Fc␥ receptor polymorphisms for the outcome of antibody therapy in NSCLC may trigger novel approaches to enhance antibody efficacy in this difficult-to-treat tumor entity because the interactions between Fc␥ receptors and therapeutic antibodies are amenable to antibody engineering. 8For example, Fc-engineered EGFR antibodies triggered killing of KRAS-mutated tumor cells that were resistant to growth inhibition and ADCC by wild-type EGFR antibodies. 9
Infection of an Established Mouse Cell Line With Cell-Free Rauscher Leukemia Virus. I. Cytological Study With the Electron Microscope&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;
Authors: H C Chopra, G P Shibley
Journal: JNCI Journal of the National Cancer Institute (1967)

Infecting mouse bone marrow cells (JLS-V9) with cell-free Rauscher leukemia virus demonstrated that monolayers of JLS-V9 cells were susceptible to infection with both cell-free plasma and tissue-culture-propagated Rauscher virus. The infected cultures maintained the continuous release of the virus. Cells and concentrated supernatant fluids from infected cells were periodically examined under the electron microscope by thin sectioning and negative staining techniques after inoculation with either mouse plasma or tissue-culture-propagated virus. After adsorption the virus underwent a prolonged eclipse or latent period. Virus budding was initially detected about 10 days after primary infection. These observations were further confirmed by the simultaneous appearance of extracellular virus. The budding process was followed by accelerated virus multiplication which reached maximum production 2-3 weeks later. Before the onset of budding no significant morphologic changes were seen in the infected cells.
Clinical Illness and Outcomes in Patients with Ebola in Sierra Leone
Authors: John S. Schieffelin, Jeffrey G. Shaffer, Augustine Goba, Michael Gbakie, Stephen K. Gire, Andres Colubri, Rachel S.G. Sealfon, Lansana Kanneh, Alex Moigboi, Mambu Momoh, Mohammed Fullah, Lina M. Moses, Bethany L. Brown, Kristian G. Andersen, Sarah Winnicki, Stephen F. Schaffner, Daniel J. Park, Nathan L. Yozwiak, Pan-Pan Jiang, David Kargbo, Simbirie Jalloh, Mbalu Fonnie, Vandi Sinnah, Issa French, Alice Kovoma, Fatima K. Kamara, Veronica Tucker, Edwin Konuwa, Josephine Sellu, Ibrahim Mustapha, Momoh Foday, Mohamed Yillah, Franklyn Kanneh, Sidiki Saffa, James L.B. Massally, Matt L. Boisen, Luis M. Branco, Mohamed A. Vandi, Donald S. Grant, Christian Happi, Sahr M. Gevao, Thomas E. Fletcher, Robert A. Fowler, Daniel G. Bausch, Pardis C. Sabeti, S. Humarr Khan, Robert F. Garry
Journal: New England Journal of Medicine (2014)

Limited clinical and laboratory data are available on patients with Ebola virus disease (EVD). The Kenema Government Hospital in Sierra Leone, which had an existing infrastructure for research regarding viral hemorrhagic fever, has received and cared for patients with EVD since the beginning of the outbreak in Sierra Leone in May 2014.
PMO-151 Excellent disease free and overall survival rates after long term follow-up of a cohort of injecting drug users treated for HCV: Abstract PMO-151 Figure 1
Authors: H Lewis, M Wilkinson, J Dalton, H Gardner, J Hothi, N Ibrahim, K King, M Mirza, A Tippett, J Turton, C Woods, S Wynne, R Igbe, G R Foster
Journal: Gut (2012)

<h3>Introduction</h3> Hepatitis C virus (HCV) is common in injecting drug users (IDU9s), but &lt;10% of those known to be infected are currently treated. Antiviral therapy for injecting drug users with HCV in North East London is provided by a Blood Borne Virus nursing team based in community outreach clinics. We aimed to examine HCV and drug related outcomes in patients treated by this service. <h3>Methods</h3> A retrospective notes analysis was performed of all patients treated between September 2006 and June 2011. Data were collected on demographics, HCV treatment, health and social outcomes. Minitab 16 and Prism 5 were used to perform statistical analysis. The Wilcoxon signed rank test, unpaired T test, and Mann–Whitney test were used to analyse drug and alcohol and demographic outcomes. <h3>Results</h3> 152 patients were treated. 77 were active IDU9s and 75 were ex-IDU9s. 80% were male. 45% were genotype 1, 54% were genotype 2 or 3. 81% of patients were compliant with treatment. 105 patients (69%) achieved an end of treatment response (ETR) Sustained viral response (SVR) rate was 58%. Overall survival post SVR was 100% and HCV free survival was 98%. Two patients were re-infected at 14 and 51 months after treatment (See Abstract PMO-151 figure 1) five deaths occurred 21, 32, 35, 37 and 44 months after treatment finished. All deaths were in non-responders. No deaths were attributable to treatment. There was no significant difference in demographics or treatment outcomes between active and ex-IDU9s. Full data on heroin injection use was available in 133 patients, crack use in 58 patients and alcohol in 72 patients. Overall heroin injection use pre- and post-treatment reduced from 51% of patients to 38% (p&lt;0.0001), crack use reduced from 34% to 19% (p&lt;0.0001), and alcohol use from 38% to 32% (p=0.0035). <h3>Conclusion</h3> This is the largest study published to-date examining the impact of antiviral therapy in patients actively using illicit drugs. Of importance long term follow-up data showing low re-infection rates, a significant reduction in illicit drug use after therapy and excellent disease free and overall survival in patients who achieve SVR is presented. Our findings confirm previous, small scale studies showing that effective treatment for injectors is possible within the appropriate clinical setting. <h3>Competing interests</h3> None declared.
Empirically Derived Decision Trees for the Treatment of Late-Life Depression
Authors: Carmen Andreescu, Benoit H. Mulsant, Patricia R. Houck, Ellen M. Whyte, Sati Mazumdar, Alexandre Y. Dombrovski, Bruce G. Pollock, Charles F. Reynolds
Journal: American Journal of Psychiatry (2008)

Objective: Several predictors of treatment response in late-life depression have been reported in the literature. The aim of this analysis was to develop a clinically useful algorithm that would allow clinicians to predict which patients will likely respond to treatment and thereby guide clinical decision making. Method: A total of 461 patients with late-life depression were treated under structured conditions for up to 12 weeks and assessed weekly with the 17-item Hamilton Rating Scale for Depression (HAM-D-17). The authors developed a hierarchy of predictors of treatment response using signal-detection theory. The authors developed two models, one minimizing false predictions of future response and one minimizing false predictions of future nonresponse, to offer clinicians two clinically useful treatment algorithms. Results: In the first model, early symptom improvement (defined by the relative change in HAM-D-17 total score from baseline to week 4), lower baseline anxiety, and an older age of onset predict response at 12 weeks. In the second model, early symptom improvement represents the principal guide in tailoring treatment, followed by baseline anxiety level, baseline sleep disturbance, and—for a minority of patients—the adequacy of previous antidepressant treatment. Conclusions: Our two models, developed to help clinicians in different clinical circumstances, illustrate the possibility of tailoring the treatment of late-life depression based on clinical characteristics and confirm the importance of early observed changes in clinical status.
Dislocation of Metatarso -- Tarsal Joints
Authors: W. D. Park
Journal: BMJ (1947)

collapse was less, profound pain had greatly increased.It was spasmodic in character, causing him to cry out and to grip his abdominal wall.Generalized abdominal rigidity was noted during the attacks of pain, but in the intervals guarding was only apparent around the umbilicus, there was no visible peristalsis, and the abdomen was silent on auscultation.Lieut.-Col.W. Brindle, R.A.M.C., was called in consultation, and made a diagnosis of mesenteric thrombosis; he recom- mended surgical intervention.By 10 a.m., after administration of 21 pints (1.42 1.) of plasma, the patient's general condition improved; his pulse rate was 110 and his blood pressure 98/70.Operation.-MajorWard, R.A.M.C., induced anaesthesia with 0.5 g. of thiopentone and continued with gas-and-oxygen.In addition the tissues of the abdominal wall were infiltrated with 2 % " novocain."A midline incision extending 4 in.(10 cm.) above and below the umbilicus was employed, and on incising the peritoneum much blood-stained fluid escaped.Distended coils of chocolate-coloured small intestine with oedematous haemorrhagic mesentery presented and were delivered from the wound.The peritoneal coat of the damaged gut still retained the normal sheen, but the upper and lower limits of devitalization were sharply demarcated.Bowel clamps were applied to healthy intestine 2 in.(5 cm.) above and below the involved segment and resection was rapidly performed.The mesentery was clamped and removed at its base beyond the areas of most intense haemorrhage.In all 91 in.(231 cm.) of gut was removed, and repair was effected by means of an end-to-end anastomosis.The omentum was sutured around the junction and over the mesenteric stump.The abdominal cavity was then mopped dry, and the abdominal wall was closed in layers without drainage.Post-operative Treatment and Progress.-Continuousgastric suction was instituted, and 2 pints (1.14 1.) of whole blood was administered.Injections of morphine 1/4 gr.(16 mg.), were given four-hourly during the first 24 hours.By the following day the patient's general condition was much improved.His
Noninvasive measurements of coronary collateral flow velocity using transthoracic doppler echocardiography
Authors: Nozomi Watanabe, Yasuko Yamaura, Maki Akiyama, Yoji Neishi, Yuji Koyama, Shuichiro Kaji, Yasuhiro Saito, Norio Kamiyama, Ryoji Suetsuna, Takashi Akasaka, Kiyoshi Yoshida
Journal: Journal of the American College of Cardiology (2002)
Clinical outcome of patients with brain metastases from HER2-positive breast cancer treated with lapatinib and capecitabine
Authors: G. Metro, J. Foglietta, M. Russillo, L. Stocchi, A. Vidiri, D. Giannarelli, L. Crinò, P. Papaldo, M. Mottolese, F. Cognetti, A. Fabi, S. Gori
Journal: Annals of Oncology (2010)
Beta 2 adrenergic receptor gene restriction fragment length polymorphism and bronchial asthma.
Authors: M Ohe, M Munakata, N Hizawa, A Itoh, I Doi, E Yamaguchi, Y Homma, Y Kawakami
Journal: Thorax (1995)

BACKGROUND--Beta 2 adrenergic dysfunction may be one of the underlying mechanisms responsible for atopy and bronchial asthma. The gene encoding the human beta 2 adrenergic receptor (beta 2ADR) has recently been isolated and sequenced. In addition, a two allele polymorphism of this receptor gene has been identified in white people. A study was carried out to determine whether this polymorphism is functionally important and has any relation to airways responsiveness, atopy, or asthma. METHODS--The subjects studied were 58 family members of four patients with atopic asthma. Restriction fragment length polymorphism (RFLP) with Ban-I digestion of the beta 2ADR gene was detected by a specific DNA probe with Southern blot analysis. Airways responses to inhaled methacholine and the beta 2 agonist salbutamol, the skin prick test, and serum IgE levels were also examined and correlated to the beta 2ADR gene RFLP. In addition, measurements of cAMP responses to isoproterenol in peripheral mononuclear cells were performed in 22 healthy subjects whose genotype for beta 2ADR was known. RESULTS--A two allele polymorphism (2.3 kb and 2.1 kb) of the beta 2ADR gene was detected in the Japanese population. Family members without allele 2.3 kb (homozygote of allele 2.1 kb) had lower airways responses to inhaled salbutamol than those with allele 2.3 kb. The incidence of asthma was higher in those without allele 2.3 kb than in those with allele 2.3 kb. The beta 2ADR gene RFLP had no relation to airways responses to methacholine and atopic status. cAMP responses in peripheral mononuclear cells of the subjects without allele 2.3 kb tended to be lower than those of the subjects with allele 2.3 kb. CONCLUSIONS--These results suggest that Ban-I RFLP of the beta 2ADR gene may have some association with the airways responses to beta 2 agonists and the incidence of bronchial asthma.
Red flags to screen for malignancy and fracture in patients with low back pain: systematic review
Authors: A. Downie, C. M. Williams, N. Henschke, M. J. Hancock, R. W. J. G. Ostelo, H. C. W. de Vet, P. Macaskill, L. Irwig, M. W. van Tulder, B. W. Koes, C. G. Maher
Journal: BMJ (2013)

Objective To review the evidence on diagnostic accuracy of red flag signs and symptoms to screen for fracture or malignancy in patients presenting with low back pain to primary, secondary, or tertiary care. Design Systematic review. Data sources Medline, OldMedline, Embase, and CINAHL from earliest available up to 1 October 2013. Inclusion criteria Primary diagnostic studies comparing red flags for fracture or malignancy to an acceptable reference standard, published in any language. Review methods Assessment of study quality and extraction of data was conducted by three independent assessors. Diagnostic accuracy statistics and post-test probabilities were generated for each red flag. Results We included 14 studies (eight from primary care, two from secondary care, four from tertiary care) evaluating 53 red flags; only five studies evaluated combinations of red flags. Pooling of data was not possible because of index test heterogeneity. Many red flags in current guidelines provide virtually no change in probability of fracture or malignancy or have untested diagnostic accuracy. The red flags with the highest post-test probability for detection of fracture were older age (9%, 95% confidence interval 3% to 25%), prolonged use of corticosteroid drugs (33%, 10% to 67%), severe trauma (11%, 8% to 16%), and presence of a contusion or abrasion (62%, 49% to 74%). Probability of spinal fracture was higher when multiple red flags were present (90%, 34% to 99%). The red flag with the highest post-test probability for detection of spinal malignancy was history of malignancy (33%, 22% to 46%). Conclusions While several red flags are endorsed in guidelines to screen for fracture or malignancy, only a small subset of these have evidence that they are indeed informative. These findings suggest a need for revision of many current guidelines.
Effect of growth hormone therapy on nitric oxide formation in cystic fibrosis patients
Authors: C. Grasemann, F. Ratjen, D. Schnabel, E. Reutershahn, U. Vester, H. Grasemann
Journal: European Respiratory Journal (2007)

Airway nitric oxide production is decreased in cystic fibrosis. As growth hormone therapy has been shown to increase nitric oxide production in growth hormone-deficient patients, it may also affect nitric oxide production in patients with cystic fibrosis. The objective of the present study was to investigate the effect of growth hormone therapy on systemic and airway nitric oxide formation in patients with cystic fibrosis. Nitric oxide metabolites in serum and urine, amino acid concentrations in serum and sputum, as well as exhaled nitric oxide, were measured in children with cystic fibrosis before, during and after 1 yr of treatment with human growth hormone. Nitric oxide metabolite concentrations increased significantly in serum and urine during the treatment period. Serum amino acid concentrations (including l -arginine, the substrate for nitric oxide synthases) also increased during treatment. The systemic bioavailability of l -arginine for nitric oxide synthases, expressed as ratio of l -arginine/ l -ornithine+lysine, remained unchanged. In contrast, l -arginine concentrations in sputum decreased significantly during growth hormone treatment, as did exhaled nitric oxide levels. Treatment with growth hormone in children with cystic fibrosis decreases exhaled nitric oxide by reducing the concentration of l -arginine in the airways.
Clinical Relevance of Conditional Survival of Cancer Patients in Europe: Age-Specific Analyses of 13 Cancers
Authors: Maryska L.G. Janssen-Heijnen, Adam Gondos, Freddie Bray, Timo Hakulinen, David H. Brewster, Hermann Brenner, Jan-Willem W. Coebergh
Journal: Journal of Clinical Oncology (2010)

Purpose When cancer survivors wish to receive accurate information on their current prognosis during follow-up, conditional 5-year relative survival may be most suitable. We have estimated conditional 5-year relative survival for 13 cancers using a large European database—European Network for Indicators on Cancer (EUNICE)—of 10 dedicated long-standing cancer registries across Europe. Patients and Methods Patients age 15 years and older diagnosed between 1985 and 2004 were included. Conditional 5-year relative survival for each age group was computed for every additional year survived up to 10 years. Period analysis with follow-up period 2000 to 2004 was used. Results All patients with cutaneous melanoma or colorectal, endometrial, or testis cancer and younger patients with stomach, glottis, cervix, ovary, or thyroid cancer or non-Hodgkin's lymphoma exhibited hardly any excess mortality (conditional 5-year relative survival &gt; 95%) given that they were alive at a defined time point within 10 years of initial diagnosis. However, patients with supraglottis, lung, breast, and kidney cancer, as well as older patients with most cancers exhibited substantial excess mortality (conditional 5-year relative survival &lt; 90%). Initial differences in relative survival at diagnosis between age groups largely disappeared with time since initial diagnosis for melanoma, or stomach, colorectal, corpus uteri, or testicular cancer but persisted for patients diagnosed with other tumors. Differences between stage groups became smaller over time or disappeared. Conclusion Conditional relative survival shows clinically relevant variations according to time since diagnosis, type of cancer, and age, and can help serve as a guide for cancer survivors in planning for their future and for doctors in planning schedules for surveillance.