tbuckley/cabot-search huggingface dataset:
Relationship of Success in Classical Immunotherapy to the Relative Immunorejective Strength of the Tumor&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: A E Reif
Journal: JNCI Journal of the National Cancer Institute (1986)

Six tumors of varying immunorejective strengths were used to compare the response of their isogenic hosts to standardized regimens of immunoprophylaxis and immunotherapy. The tumors were generated spontaneously or induced chemically [with 9,10-dimethyl-1,2-benzanthracene (CAS: 57-97-6)], virally (with murine leukemia virus), or radiogenically (with strontium-90). The hosts were C57BL/6J or BALB/cByJ mice. Immunoprophylaxis and immunotherapy were performed with isogenic irradiated tumor cells, withCorynebacterium parvum, or with both. The results of challenge experiments were quantified as the doses of viable tumor cells that produced 50% tumor deaths for immunized and for control mice. The results for these quantitative “classical” immunoprophylaxis and immunotherapy experiments were consistent with two theses: 1) that only immunorejective tumors give positive results with classical immunotherapy and 2) that classical immunoprophylaxis is more effective than classical immunotherapy when identical materials are used for immunizations. These results have important consequences for the clinical use of classical immunotherapy.
Intestinal Alkaline Phosphatase Activity in Familial Hypophosphatasia
Authors: Stuart H. Danovitch, Paul N. Baer, Leonard Laster
Journal: New England Journal of Medicine (1968)

Homogenates of small-Intestine mucosa obtained from members of a family with hypophosphatasia were assayed for alkaline phosphatase activity with four phosphate esters. The results were compared to those obtained for 14 control subjects. In one patient with clinical and biochemical manifestations of hypophosphatasia intestinal alkaline phosphatase activity for each substrate was either normal or elevated. Five relatives with only the biochemical abnormalities of the disease also had normal or elevated intestinal activities. Of two relatives with no apparent clinical or biochemical involvement, one had normal, and one had elevated intestinal alkaline phosphatase activities. The results show that, contrary to previous impressions, alkaline phosphatase activity is not uniformly reduced in all tissues in all patients with hypophosphatasia. These tissue differences may reflect differences in genetic control mechanisms.
A Girl With Marfanoid Habitus and Distinctive Orolabial Lesions
Authors: Nicole Knöpfel, Ana Martín-Santiago, Elsa Puerto-Carranza
Journal: JAMA Dermatology (2016)

An adolescent girl with no relevant family history was referred to the dermatology pediatric unit for evaluation of multiple asymptomatic lesions on her tongue that gradually developed since the first years of life; both lips were enlarged and felt nodular. What is your diagnosis?
Exosome-Transmitted lncARSR Promotes Sunitinib Resistance in Renal Cancer by Acting as a Competing Endogenous RNA
Authors: Le Qu, Jin Ding, Cheng Chen, Zhen-Jie Wu, Bing Liu, Yi Gao, Wei Chen, Feng Liu, Wen Sun, Xiao-Feng Li, Xue Wang, Yue Wang, Zhen-Yu Xu, Li Gao, Qing Yang, Bin Xu, Yao-Ming Li, Zi-Yu Fang, Zhi-Peng Xu, Yi Bao, Deng-Shuang Wu, Xiong Miao, Hai-Yang Sun, Ying-Hao Sun, Hong-Yang Wang, Lin-Hui Wang
Journal: Cancer Cell (2016)
Evaluation of gammadelta T cells as antigen-presenting cells for cancer immunotherapy.
Authors: A. Yamasaki, H. Onishi, T. Morisaki, M. Tanaka, M. Katano
Journal: Journal of Clinical Oncology (2010)

e21068 Background: Gammadelta T cells (γδ T cells), a subset of T cells, are involved in protective immunity system through cytokine secretion and cytotoxic activity. Recently, γδ T cells also have been reported to display characteristics of professional antigen presenting cells (APCs). This ability of γδ T cells to present antigens gives an opportunity to develop highly feasible cancer immunotherapy. Puropose:To examine proliferative activity and antigen presenting ability of γδ T cells for clinical application to cancer immunotherapy. Methods: We evaluated following items using peripheral blood mononuclear cells (PBMCs) of 35 advanced cancer patients. 1) To analyze proliferative activity of gd T cells: PBMCs were stimulated with either zoledronate (ZOL) or pyrophosphate (2M3B1PP) in the presence of IL-2 for 10 days. Total number of γδ T cells was counted with flow cytometry. 2) To analyze antigen presenting ability of γδ T cells: Firstly, expression of antigen presentation-related molecules on proliferating gd T cells was determined with flow cytometry. Secondly, inducible ability of cytotoxic T cells (CTL) by gd T cells was examined. Briefly, CD8+ T cells isolated from HLA-A24-positive patients were stimulated with HLA-A24-restricted CEA peptide -pulsed gd T cells. Ten days after the culture, CD8+ T cells were cocultured with HLA-A24-positive CEA-positive cancer cells. Induction of CTL was estimated by 51Cr release assay and ELISA. Results: 1) Number of gd T cells in PBMCs distinctly increased with either ZOL or 2M3B1PP in 32 patients. 2) Those proliferating gd T cells overexpressed HLA-DR, CD80 and CD86 molecules, which were indispensable to antigen presentation. 3) CD8+ T cells pre-stimulated with HLA-A24-restricted CEA peptide-pulsed gd T cells killed HLA-A24-positive CEA-positive cancer cells significantly compared to CD8+ T cells pre-stimulated with non-pulsed gd T cells or just CD8+ T cells. Those CD8+ T cells also induced a large amount of INF-g production. Conclusions: We could get a large number of gd T cells, which have sufficient antigen presenting ability, from cancer patients' PBMCs. Thus, gd T cells may become useful tool as a new antigen presenting cells for cancer immunotherapy. No significant financial relationships to disclose.
PTH-097 Notch1 is a master regulator of the senescence secretome through repression of c/ebpΒ
Authors: M Hoare, Y Ito, T-W Kang, S Menon, R Salama, L Zender, M Narita
Journal: Gut (2015)

<h3>Introduction</h3> Oncogene-induced senescence (OIS) is an intrinsic tumour suppressor mechanism, but its impact on tumorigenesis is largely dependent on the nature of SASP, senescence-associated secretory phenotype. Major components of the SASP include TGFβ1 and pro-inflammatory cytokines, such as IL1A, IL6, and IL8 that have pleiotropic context-dependent effects. <h3>Method</h3> We utilised the well validated ER:Ras<sup>G12V</sup>IMR90 HDF <i>in vitro</i>model which undergo Ras-induced senescence (RIS) with 4OHT. <i>In vivo</i>hepatocyte RIS was achieved with hydrodynamic tail-vein injection of NRas<sup>G12V</sup>-containing transposons. <h3>Results</h3> Previously, we have shown that Notch1, a highly conserved receptor is up-regulated in RIS. In contrast to the up-regulation of Notch1, downstream signalling is dynamically regulated; Notch-target genes were transiently up-regulated at an early phase of RIS, but down-regulated at full senescence. The dynamic expression pattern of N1ICD and TGF-β1 expression were nearly identical, and inversely correlated with the cytokines, IL1A and IL8. Inhibition of Notch1 signalling, through expression of a dominant-negative form of the Notch1 binding partner MAML1, led to a reduction in TGF-β1, but increased IL1A and IL8 expression during RIS, suggesting Notch1 signalling plays a critical role in secretome switching. It has been shown that the SASP in RIS is regulated by two major transcription factors, NFkB and CEBPβ. Strikingly, over-expression of N1ICD strongly down-regulated CEBPβ, but not NFkB, in fully established RIS cells. Further, expression of ectopic CEBPβ in N1ICD-expressing cells partially restored levels of IL6/8. N1ICD was also able to suppress pro-inflammatory cytokine expression in TNF-α stimulated cells, through repression of CEBPβ. These data indicate that Notch1 represses pro-inflammatory cytokines by down-regulating CEBPβ. Finally, Notch1 up-regulation in OIS was confirmed in Nras-driven hepatocyte senescence; Notch1 inhibition through dnMAML1 promoted immune-mediated clearance of senescent hepatocytes. <h3>Conclusion</h3> We propose that the transition to OIS is correlated with a switch from Notch1-driven TGFβ-rich secretome to a CEBPβ-driven IL1/8 rich secretome, and that dynamic Notch1 signalling modulates senescence and its long-term fate strictly through a non-cell-autonomous fashion. <h3>Disclosure of interest</h3> None Declared.
Preoperative Transcatheter Closure of Congenital Muscular Ventricular Septal Defects
Authors: Nancy D. Bridges, Stanton B. Perry, John F. Keane, Steven A.N. Goldstein, Valerie Mandell, John E. Mayer, Richard A. Jonas, Aldo R. Casteneda, James E. Lock
Journal: New England Journal of Medicine (1991)

Surgical repair of muscular ventricular septal defects, particularly those associated with complex heart lesions carries a higher risk of reoperation and death than the repair of membranous defects. Closing a muscular defect through an incision in the systemic ventricle may cause late ventricular dysfunction. In a collaborative approach to this problem, we undertook preoperative transcatheter closure of muscular ventricular septal defects remote from the atrioventricular and semilunar valves, followed by the surgical repair of associated conditions.In 12 patients selected jointly by a cardiologist and a cardiac surgeon, we attempted preoperative transcatheter umbrella closure of 21 defects. Half the patients had associated complex heart lesions; the others had had pulmonary-artery banding to reduce the amount of left-to-right shunting. Half had severe ventricular septal deficiency.All 21 defects were successfully closed without major complications. Subsequent cardiac surgery for associated conditions in 11 of the 12 patients resulted in a mean pulmonary-to-systemic flow ratio of 1.1, indicating minimal residual left-to-right shunting; 1 patient awaited surgical repair. No deaths, reoperations, or late complications have occurred after a follow-up of 7 to 20 months.A collaborative approach using transcatheter closure followed by the surgical repair of associated cardiac lesions may decrease rates of operative mortality, reoperation, and left ventricular dysfunction in patients with muscular ventricular septal defects.
P213 CXR follow-up after Community Acquired Pneumonia (CAP): Outcomes of adherence to guidelines
Authors: P Eaton, HJ Curtis
Journal: Thorax (2015)

<h3>Introduction and objectives</h3> BTS Community Acquired pneumonia (CAP) guidelines require a chest radiograph (CXR) 6 weeks after discharge in high risk patients. This is the hospital team’s responsibility. Malignancy is reported in 1.7% of patients. We wanted to assess how this was organised across our trust and the outcomes, aiming to improve organisation of the service. <h3>Methods</h3> Patients were identified via retrospective review of local NIV/COPD and critical care ICNARC databases. Xrays and reports were reviewed and eRecords interrogated for appointments, follow-up CXR and outcomes. <h3>Results</h3> 102 patients were identified between December 2013 to January 2015, (mean age 69 and 56 female patients). Only 54 patients had the follow up CXR. 16 patients did not need local follow-up for a variety of reasons: co-morbidities; current malignant diagnosis; CXR clear pre-discharge or usual residence outside geographical area. 7 patients did not attend the organised follow up appointment. Ultimately, 25 patients had no follow up plans made. The majority of follow-up CXR were organised by the hospital team (n = 53) compared to discharge correspondence instructions to GP to request a CXR (n = 14). The hospital requested CXR were significantly more likely to be undertaken, with 88% completed versus 57% from requests to GP (p &lt; 0.05 Chi-square). The majority of CXRs showed resolution of changes (n = 38/54), 3 patients had lung or pleural malignancy diagnosed, 2 patients are having on-going nodule follow-up and 1 patient had atypical mycobacterium diagnosed. 10 patients to date have incomplete resolution of their changes. These end-points were after 62 CXRs, 7 Ct scans, 2 bronchoscopies and 1 pleural biopsy. <h3>Conclusion</h3> There is room for improvement within our trust to improve this parameter for CAP patients. This would be best fulfilled by automatic request at time of discharge follow CAP. The follow up clearly requires increasing amounts of work and administration. How does the NHS keep up with guideline requirements and clinical outcomes in the ageing population? The finding of 5.5% (3/54) new malignancy shows the importance of follow-up and is higher than published reports.
Preliminary clinical outcomes and dosimetry study on adaptive IMRT integrated HDR brachytherapy in local advanced uterine cervical cancer.
Authors: Jinyi Lang, Weidong Wang, Zhiru Li, Gang Yin, Pei Wang, Binyu Fu
Journal: Journal of Clinical Oncology (2013)

e16520 Background: To analyze the dosimetry features of adaptive IMRT integrated 3D-HDR brachytherapy in local advanced cervical carcinoma and report its preliminary clinical results. Methods: From 2009.06 to 2012.06, patients with cervical carcinoma (IIb-IIIb by FIGO staging) in Sichuan Cancer Hospital were treated with IMRT firstly in a 45Gy/25f/5w fraction modal, replanning at 30Gy adapting to the volume alterations of cervical lesions. Subsequently, adaptive IMRT integrated 3D-HDR brachytherapy was applied to boost the dosage of residual cervical lesions, MRI/CT scanning and replanning for each fraction, 6 (8Gy/f×4) 6f. Concurrent chemotherapy with DDP 40 mg/m 2 , was used weekly in the full course. The DVH data were collected for dosimetry analysis. The acute and late side effects, early responses and long term efficacy were evaluated for these group of patients. Results: Seventy-nine patients with local advanced cervical cancer were recruited in this study with a median age of 50yr (29-70yr) and median follow-up of 25mons (6-34mons). Dosimetry analysis demonstrated that IMRT-HDR not only yielded substantially improved high-risk CTV coverage (average V95 = 96.2%), but also kept the doses to the bladder (D1cc 69 (76Gy) and rectum(D1cc 63 (70Gy) reasonably low. Out of this group of patients, 87.8% reached complete response (CR) and 12.2% partial response (PR). Two-year follow-up showed that local control rate (LC), distant-metastasis free survival rate (DMFS), overall survival rate (OS) was 93.2%, 86.4% and 87.5%,respectively. Blood toxicity was the main early side effect with a 37.5% grade III-IV (RTOG), mild toxicities occurred in bladder (grade I/II 24.2%) and rectum (grade I/II 26.6%). Late side effects were found in 3 patients (2 radiocystitis, 1 intestinal obstruction). Conclusions: IMRT integrated adaptive 3D-HDR brachytherapy is a feasible way to boost the dosage of cervical lesions,preliminary clinical evaluation showed a better outcome and tolerable side effects.
A microRNA-based diagnostic test for kidney tumors classification.
Authors: A. Chajut, E. Fridman, I. Barshack, Z. A. Dotan, M. Zepeniuk, S. Tabak, D. Lebanony, E. Klinke, S. Rosenwald, O. Zion, A. Faerman, M. Ben-David, A. Bokish, Y. Spector
Journal: Journal of Clinical Oncology (2011)

10578 Background: Renal cancers account for more then 3% of adult malignancies and cause more than 13,000 deaths per year in the U.S. alone. The four most common types of kidney tumors include the malignant renal cell carcinomas clear cell (conventional), papillary and chromophobe as well as the benign oncocytoma. These histological subtypes vary in their clinical courses and their prognosis, and different clinical strategies have been developed for their management. In some of the kidney tumor cases it is difficult for the pathologist to distinguish between tumor types on the basis of morphology. In this work we present a microRNA-based differential diagnosis test for primary kidney tumors. Methods: Over 200 formalin-fixed paraffin-embedded (FFPE) samples of primary kidney tumors were collected and reviewed by a pathologist with special experience in uropathology. High-quality totalRNA, including the well-preserved microRNA fraction, was extracted from the FFPE samples using a proprietary protocol. Expression levels of all known and additional Rosetta’s proprietary microRNAs were profiled using a custom array platform. Technical validation of the array results was performed using qRT-PCR. An assay which classifies the kidney tumors was developed based on the microRNAs expression in the different tumor types. A validation set of more than 150 independent samples was analyzed blindly and classified using the developed assay. Results: MicroRNAs showed differential expression in the four main histological types mentioned above with high correlation between the array and the qRT-PCR platforms. A set of microRNAs was identified that allows accurate classification of kidney tumors. A diagnostic assay based on the array technology was developed and clinical validation performed using an independent, blinded sample set. Conclusions: Expression levels of certain microRNAs are highly specific to subtypes of kidney tumors. These findings were the basis for the development of a standardized diagnostic assay that can be used for the classification of kidney tumors in FFPE samples from resections or biopsies.
Some determinants of maternal attachment
Authors: G H Peterson, L E Mehl
Journal: American Journal of Psychiatry (1978)

The authors conducted prenatal interviews and behavior observation sessions with 46 families in which the woman was pregnant. These families were again interviewed and observed 7 days, 1 month, 2 months, and 6 months after the child was born. The authors found that the most significant variable predicting the variance of maternal attachment was the length of separation of mother and infant: less separation was associated with greater attachment. The next most significant variable was birth experience, followed in importance by the length of labor and prenatal attitudes and expectations.
S40 Optimisation of a human BCG challenge model
Authors: MEM Wilkie, A Minhinnick, S Harris, J Peter, L Stockdale, ZR Manjaly-Thomas, S Vermaak, I Satti, P Moss, H McShane
Journal: Thorax (2015)

<h3>Introduction</h3> Tuberculosis remains a significant global disease burden with an estimated 9 million new cases and 1.5 million deaths in 2013. BCG continues to be the only licensed TB vaccine, however it is poorly efficacious against adult pulmonary TB disease and there is a desperate need for a better vaccine to provide greater and more consistent protection. Development of such a vaccine has been hampered by the lack of reliable and validated correlates of protection. A human mycobacterial challenge model, using BCG as a surrogate for Mycobacterium tuberculosis challenge would facilitate improved vaccine selection for progression into future field efficacy testing. In this study we evaluate the effect of two BCG strains at two doses to optimise this model. <h3>Methods</h3> 40 healthy BCG-naïve adults were assigned to one of four groups to receive intradermal BCG SSI or BCG Tice at standard or high dose. Two weeks following BCG challenge, skin biopsy from the BCG challenge site was performed. Volunteers were followed up for 28 days from challenge to assess reactogenicity and ensure no safety concerns. BCG mycobacterial load was quantified by solid culture and quantitative PCR. <h3>Results</h3> BCG, regardless of strain or dose, was tolerated well and reactogenicity was similar between groups. BCG strain did not significantly affect BCG recovery from skin biopsy, however there was significantly greater recovery from the high dose challenge groups compared with the standard dose. Consistent with previous findings there was an inverse correlation between ex-vivo IFN-γ ELISpot responses to PPD and amount of BCG recovered from the skin biopsies. <h3>Conclusions</h3> High dose BCG challenge regardless of strain used, significantly improves the sensitivity of this human mycobacterial challenge model. Practical reasons favour the use of BCG SSI over BCG Tice, as BCG SSI is licensed for intradermal administration in the UK and preparation is more straightforward with less product wastage or variability in dose between vials of BCG SSI. Looking ahead we plan to use this optimised BCG SSI challenge model to evaluate novel TB vaccine candidates in order to improve the selection of which vaccines then progress to expensive field efficacy trials.
Urinary-Tract Infections in Schoolchildren
Authors: Calvin M. Kunin, Elizabeth Zacha, Albert J. Paquin
Journal: New England Journal of Medicine (1962)

THE quantitative enumeration of bacteria in the urine has proved to be a useful procedure in the diagnosis of infections of the urinary tract in hospital and office practice1 2 3 4 5 6 and is being employed as an epidemiologic tool in investigations of the distribution of these infections in relatively asymptomatic populations.7 8 9 10 11 12 13 14 15 16 Most of the data accumulated thus far, with a few exceptions,9 , 11 , 14 15 16 have been obtained from studies of hospital and clinic patients and, although useful, may not accurately reflect the prevalence or severity of urinary-tract infections in the general population.In 1960 a pilot study of the prevalence of urinary-tract infections among . . .
Isoniazid Dosage in Patients with Renal Failure
Authors: D. Ward Bowersox, Richard H. Winterbauer, George L. Stewart, Burton Orme, Edward Barron
Journal: New England Journal of Medicine (1973)

ALTHOUGH isoniazid has been used in antituberculous therapy for 20 years, the influence of renal failure on isoniazid excretion has never been established. Paradoxically, this gap in medical knowledge continues despite expanded indications for the use of the drug in patients with renal failure. For example, the American Thoracic Society ad Hoc Committee on chemoprophylaxis has included tuberculin-positive patients with a variety of chronic renal diseases in their recommendations for isoniazid prophylaxis.1 In patients with normal renal function 50 to 80 per cent of a dose of isoniazid is excreted in the urine in 24 hours.2 3 4 5 Part of the drug . . .
Identification of radioresistant genes in oral cancer cells
Authors: Ting-yang Lin, Ann-joy Cheng
Journal: Cancer Research (2008)

AACR Annual Meeting-- Apr 12-16, 2008; San Diego, CA

1459 

In Taiwan, the incidence of oral cancer has become the 6th leading cancer, and is still increasing in recent years. Since oral cancer usually occurs in the middle age male, at the high peak of life responsibility, it has tremendous impact on family and society. Radiation therapy is an integral part of the treatment of oral cancer. However, local recurrence or tumor persistence after radiation therapy, that is radioresistant (RR) of the cancer, is the major cause of treatment failure. To investigate radioresistant mechanism, we established radioresistant (RR) subclones of two oral cancer cell lines, OEC-M1 and KB. After characterization of the radioresistant phenotype, the differential proteomes of parental and RR subclones were analyzed by gradient gel electrophoresis and identified by Mass spectrometry. Seven genes were identified as candidate RR genes. Gp96, Enolase-1 and annexin A2 were identified up-regulated in RR subclones. Heat shock protein Gp96 and TGF-s family protein GDF-15 were previously examined up-regulated in Nasopharyngeal cancer RR subclones. We investigate the role of Gp96 and GDF-15 in the radioresistance of oral cancer. gp96 and GDF-15-siRNA were constructed and transfected into oral cancer cells to examine alterations of their radiosensitivity. Prolonged radiation-induced growth delay, reduced colongenic survival, G2-M phase cell cycle arrest and enhanced ROS level were found in the gp96-siRNA transfectants. Xenograft model further demonstrates that Gp96 RNAi can serve as a radio-sensitizer for oral cancer treatment. These results demonstrate that Gp96 is involved in the radioresistant mechanisms of oral cancer. Knockdown of Gp96 may enhance radiosensitivity, which may lead to better prognosis in oral cancer treatment.