tbuckley/cabot-search huggingface dataset:
Complications of BCG Immunotherapy in Patients with Cancer
Authors: Frank C. Sparks, Melvin J. Silverstein, John S. Hunt, Charles M. Haskell, Yosef H. Pilch, Donald L. Morton
Journal: New England Journal of Medicine (1973)

Abstract Eighty-two patients with solid neoplasms were treated with BCG. BCG was well tolerated when given intradermally and alone by the multiple-puncture tine technic (24 patients) or with a tumor-cell vaccine (34 patients). Intratumor injection of BCG was associated with frequent complications, including marked malaise and an influenza-like syndrome in 16 of 25 patients, a temperature of 40°C or higher in 12, reversible hepatic dysfunction in six, and jaundice in three patients. Antituberculous chemotherapy with isoniazid promptly alleviated symptoms in seven patients so treated. BCG administration appears to be well tolerated with the multiple-puncture technic, but the intra-tumor injection of BCG may be associated with more serious side effects. (N Engl J Med 289:827–830, 1973)
Exercise-Induced Ischemia in Mildly Symptomatic Patients with Coronary-Artery Disease and Preserved Left Ventricular Function
Authors: Robert O. Bonow, Kenneth M. Kent, Douglas R. Rosing, K. K. Gordon Lan, Edward Lakatos, Jeffrey S. Borer, Stephen L. Bacharach, Michael V. Green, Stephen E. Epstein
Journal: New England Journal of Medicine (1984)

To determine prospectively whether the severity of reversible left ventricular ischemia provides prognostic information in mildly symptomatic patients with coronary-artery disease and preserved left ventricular function at rest (ejection fraction greater than 40 per cent), we studied 117 patients by means of exercise electrocardiography and radionuclide angiography. No patient had stenosis of the left main coronary artery. Mortality during subsequent medical therapy was significantly associated (by univariate life-table analysis) with three-vessel coronary-artery disease and the magnitude of the ejection fraction during exercise. In patients with three-vessel disease who had both ST-segment depression of 1 mm or more and a decrease in ejection fraction during exercise, in association with an exercise tolerance of 120 W or less, the probability of survival at four years was only 71 +/- 11 per cent (S.E.). All deaths occurred in this subgroup. Thus, objective evidence of left ventricular ischemia during exercise and exercise capacity identify one subgroup of minimally symptomatic patients with three-vessel disease with an excellent prognosis and another subgroup at relatively high risk of dying during subsequent medical therapy.
Abstract 5338: MicroRNA-CGU promotes progression and metastasis through a negative regulation of ERM protein in human gastric cancer.
Authors: Chia-Siu Wang, Ming Ming Tsai, Liang-Mou Kuo, Kwang-Huei Lin
Journal: Cancer Research (2013)

Abstract Background: miRNAs have an important role in tumor carcinogenesis. They may act either as oncogenes or tumor suppressor genes through their regulated-target genes. The aim of this study was to identify useful biomarkers from miRNAs that might regulate the tumorigenesis or progression of gastric cancer. Materials and Methods: Differential miRNA profile was analyzed with a 270 miRNAs-based qRT-PCR assay in a total of 6 pairs of tumor tissues and matched non-tumor mucosa from surgical specimens. One of the top strongest up-regulated miRNAs was selected, and it was validated by qRT-PCR in fresh frozen tissues of gastrectomized specimens from gastric cancer patients. The target gene was searched and identified. The clinicopathologic correlations of the candidate miRNA and target gene were evaluated for their clinical significance. Results: The miR-CGU significantly increases by more than 40.2-fold (p &amp;lt; 0.001) in gastric cancer tissues compared with their matched adjacent nontumorous tissues (n = 109). Overexpression of miRNA was significantly associated with tumor progression that included serosal invasion, lymph node metastasis, distant metastasis and pathological stage (all p &amp;lt; 0.001). Higher expression of miR-CGU was significantly associated with a worse 5-year survival outcome (log rank p &amp;lt; 0.001, and p = 0.005, respectively). Functional assays showed that overexpression of this miRNA enhanced gastric cancer cell migration and invasion in vitro and lung metastasis formation in vivo. In addition, a target gene, ERM protein, was identified for miR-CGU. Elevated expression of miRNA in gastric cancer cells could reduce the mRNA and protein levels of ERM protein, and vice versa. Luciferase assays confirmed that miR-CGU could directly bind to the 2-8 nucleotides of 3’ untranslated region of ERM protein. Moreover, an inverse correlation between miR-CGU and ERM protein expression was observed in gastric cancer tissues. The Interaction of miR-CGU and ERM protein expression was further studied in gastric cell lines. Conclusion: The miR-CGU is highly upreglated in gastric cancer tissues. It functions as a tumor metastasis enhancer in gastric cancer, and its overexpression contributes to lymph node metastasis and progression of gastric cancer. Overexpression of its target gene, ERM protein may have a therapeutic potential to suppress gastric cancer metastasis. Citation Format: Chia-Siu Wang, Ming Ming Tsai, Liang-Mou Kuo, Kwang-Huei Lin. MicroRNA-CGU promotes progression and metastasis through a negative regulation of ERM protein in human gastric cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 5338. doi:10.1158/1538-7445.AM2013-5338
The Effects of New Platelet Inhibitory Drug E-5510 on Platelet Deposition on Aortic Bifurcation Grafts: Assessment by Indium-111-Oxime Labeled Platelet Imaging
Authors: KAZUYOSHI SUGA, KAZUYA NISHIGAUCHI, NORIHIKO KUME, KEIKO KISHIMOTO, NAOFUMI MATSUNAGA, KENTARO FUJIOKA, NORIIYA ZEMPO, ESATO KENSUKE
Journal: Clinical Nuclear Medicine (1998)

The effects of a recently synthesized anti-platelet aggregation drug (E-5510) on platelet deposition in a knitted Dacron aortic graft underwent preliminary evaluation by In-111 oxime labeled platelet imaging. Seven patients undergoing aortofemoral bypass using this graft for occlusive disease were randomized into two groups: those receiving E-5510 and those receiving no medication. This agent was administered for 17 days postoperatively, and on the 14th day In-111 platelets were injected and images were acquired at 24, 48, and 72 hours. Platelet deposits in the grafts were assessed by the ratios of graft radioactivity to that of the adjacent native iliac arteries. Platelet deposition at the sites of anastomosis and deposition along the entire graft were normalized by initial deposition at 24 hours, and had significantly decreased at 72 hours in the three treated patients, while the normalized deposition increased progressively over time in the remaining four nonmedicated patients. E-5510 seems to have the potential to inhibit excessive platelet deposition on recently implanted grafts.
Gender differences on thought disturbance measures among schizophrenic patients
Authors: W Perry, D Moore, D Braff
Journal: American Journal of Psychiatry (1995)

This study examined gender differences on three measures of thought disturbance among patients with schizophrenia and the relation between thought disturbance and social competency.Fifty-three male and 34 female patients diagnosed with schizophrenia according to the DSM-III-R criteria were assessed on measures of thought disturbance: subscales of the Scale for the Assessment of Positive Symptoms (SAPS), subscales of the Brief Psychiatric Rating Scale (BPRS), and the Ego Impairment Index. Gender differences on the three measures of thought disturbance and the relation of these measures to demographic variables and other variables, such as social competency, were examined.Male and female schizophrenic patients demonstrated similar degrees of thought disturbance on the pertinent subscales of the SAPS and the BPRS, but the male schizophrenic patients had scores showing greater impairment on the Ego Impairment Index. Furthermore, a relationship between thought disturbance and social competency was confirmed.These findings support other studies in which female patients were found to have a "milder" form of schizophrenia, generally characterized by better social functioning, than their male counterparts. The literature regarding gender-related differences in thought disturbance in schizophrenia has been unclear and complicated by design issues such as obtaining adequate samples of subjects and optimizing measurement selection. The findings of this study suggest that use of a converging-measures strategy allows a better assessment of thought disturbance in severely ill schizophrenic patients and an understanding of the importance of thought disorder with respect to gender-related patterns of clinical characteristics, such as social competency.
Disseminated Lupus Erythematosus Occurring among Student Nurses*
Authors: L. Fred Ayvazian, Theodore L. Badger
Journal: New England Journal of Medicine (1948)

IN the course of a follow-up survey‡ on a group of 750 nurses who trained at a large municipal hospital between 1932 and 1946,1 it was found that 3 of these girls had developed and succumbed to disseminated lupus erythematosus. These cases represent 23 per cent of the total mortality among the nurses, the disease being second only to tuberculosis as the major cause of death. The deaths in the entire group have numbered 13, and have been distributed as shown in Table 1.The occurrence of lupus three times in this group is by itself a curious and unexpected finding, . . .
Abstract 4753: Targeting nucleotide excision repair: Chemical synthetic lethality and biology-based combination therapy
Authors: John J. Turchi, Jiyoon Lee, Jeremiah Hendricks, Tracy M. Neher, Richard W. Fitch
Journal: Cancer Research (2012)

Abstract As DNA repair defects in cancer can be exploited for therapeutic benefit via synthetic lethality, new DNA repair targets and compounds to inhibit them will expand the armamentarium against cancer. While most targeted therapies involve disrupting enzyme-substrate interactions we have pursued targeting protein-DNA interactions to validate an entire new class of molecular interactions that can be targeted with small molecule drugs. We have focused on the nucleotide excision repair (NER) pathway and two proteins, the single-stranded DNA binding protein, replication protein A (RPA) and the xeroderma pigmentosum group A (XPA) protein. We have identified and developed small molecule inhibitors (SMIs) of each target. In vitro analysis of XPA SMI has led to a 50-fold increase in potency and revealed structure-activity relationships that define the important pharmacophores for XPA interaction. Both reversible and irreversible SMIs of RPA have been identified and cellular analysis of irreversible RPA SMI's revealed single agent anticancer activity at sub-micro-molar concentrations. The degree of the anticancer effect of cellular RPA inhibition varied among cancer types and was dependent on the DNA repair phenotype. Synergy between NER inhibition and cisplatin will be presented and as a function of DNA repair phenotype. These data demonstrate the ability to develop SMI of protein-DNA interactions that impact DNA repair and can be employed to increase the sensitivity of repair deficient tumors to DNA damaging therapeutics. This works was supported by NIH grant R01-CA82741 to JJT Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4753. doi:1538-7445.AM2012-4753
Abstract 4215: Integrin-dependent mechanisms for sensitizing melanomas to chemotherapy
Authors: Jennifer L. Bays, Melissa Palma, Kris A. DeMali
Journal: Cancer Research (2012)

Abstract BRAF is mutated in 50-70% of human melanomas, resulting constitutive activation of the MEK-ERK1/2 signal transduction pathway and resistance to apoptosis. Agents that target the oncogenic BRAF signaling pathway are revolutionizing the treatment of metastatic melanoma. However, it is already evident that there is both intrinsic and acquired resistance to this class of compounds suggesting that combinatorial therapies may be needed to combat melanoma resistance. We recently described a novel compound, denoted vinculin activating peptide (VAP) that engages defective integrins with the extracellular matrix and consequently sensitizes melanomas to chemotherapy. VAP is relatively large and the minimal sequences required for the sensitization of melanomas to chemotherapy are not known. In this study, we investigated the smallest domains of VAP that are required for its chemosensitizing effects. Here, we report that VAP contains three small domains, termed vinculin binding sites (VBSs) which are sufficient to bind the integrin-associated protein, vinculin and sensitize melanoma cells to chemotherapeutics. Out of the three VBSs within VAP, VBS3 exhibits stronger binding to vinculin and increases cell-matrix adhesion and focal adhesion number to a greater extent. Furthermore, VBS3 enhances melanoma sensitivity to chemotherapy more than VBS1 or VBS2. The residues of VBS3 required for the sensitization of melanomas have been investigated and suggest that divergent residues are important for chemosensitization. Collectively these data suggest that small molecule mimetics of VBS3 would be an ideal therapy to overcome the resistance of metastatic melanomas to chemotherapeutic agents. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4215. doi:1538-7445.AM2012-4215
EUS-FNA for patients with suspected malignant biliary strictures after negative results by endoscopic transpapillary brush cytology or forceps biopsy
Authors: Ohshima Yasuhiro
Journal: Endoscopy (2011)

Background: Endoscopic transpapillary brush cytology or forceps biopsy is widely used for patients with suspected malignant biliary strictures. However, since the sensitivity of these methods remain insufficient, it is sometimes difficult to confirm the diagnosis of malignancy. In such cases, alternative sampling techniques are required for providing a definitive diagnosis that will aid in choosing a treatment strategy.
FRI0406 Seven-year follow-up of autologous hematopoietic stem cell transplantation for severe systemic sclerosis
Authors: H. Tsukamoto, T. Horiuchi, T. Miyamoto, H. Niiro, Y. Arinobu, M. Akahoshi, M. Ayano, A. Tanaka, N. Ueda, K. Akashi
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Autologous stem cell transplantation for international scleroderma (ASTIS) trial demonstrated that autologous hematopoietic stem cell transplantation (auto-HSCT) is more effective than conventional intravenous cyclophosphamide in the treatment of severe systemic sclerosis (SSc). However, there is paucity of the study showing the long-term efficacy of auto-HSCT for severe SSc. <h3>Objectives</h3> The aim of this study is to investigate seven-year follow-up results of auto-HSCT for severe SSc. <h3>Methods</h3> Nineteen patients (4 male and 15 female) with severe SSc were enrolled. Peripheral blood stem cells (PBSCs) were mobilized with cyclophosphamide (CY, 4 g/m<sup>2</sup>) and G-CSF. After collecting PBSCs more than 2x 10<sup>6</sup>CD34+cells/kg by apheresis, CD34+ cells were immunologically selected in 11 patients. All of the patients were treated with high-dose CY (200 mg/kg) and received CD34-selected (n=11; a group with CD34-selection) or unmanipulated (n=8; a group without CD34-selection) auto-HSCT. Immune reconstitution was evaluated serially by analyzing lymphocyte subpopulations for 36 months after HSCT. <h3>Results</h3> There was no treatment-related mortality. As toxicity, there were a variety of post-transplant infections such as adenoviral hemorrhagic cystitis, herpes zoster and cytomegaloviral antigenemia. Sclerosis of the skin was markedly improved in all of the patients within 6 months and the improvement was sustained for 84 months after auto-HSCT. Vital capacity was significantly increased at 48 and 60 months after HSCT and KL-6, a marker for interstitial pneumonia (IP), was significantly decreased in patients with IP during 12-84 months after HSCT. A titer of anti-Scl-70 was significantly decreased during 1-84 months after HSCT. Five and seven years after auto-HSCT, the overall survival was 89 and 78%, and the progression-free survival was 65 and 57%, respectively. Interestingly, the reduction of the skin scores was significantly greater and viral infections were more frequent in the patients with CD34-selection than those without. Effect of auto-HSCT on interstitial pneumonia, and the recovery of lymphocyte subpopulations after auto-HSCT were not significantly different between two groups. <h3>Conclusions</h3> Auto-HSCT was effective in the treatment of SSc and the effect was sustained for 7 years. <h3>References</h3> Tsukamoto H, Nagafuji K, Horiuchi T, et al. A Phase I-II Trial of Autologous Peripheral Blood Stem Cell Transplantation in the Treatment of Refractory Autoimmune Disease. Ann Rheum Dis. 65: 508-14, 2006. Tsukamoto H, Nagafuji K, Horiuchi T, et al. Analysis of immune reconstitution after autologous CD34+ stem/progenitor cell transplantation for systemic sclerosis: predominant reconstitution of Th1 CD4+ T cells. Rheumatology 2011; 50: 944-52. <h3>Disclosure of Interest</h3> None Declared
Abstract B54: Identification of the PI3K-mTOR pathway as regulator of mutant p53 turnover in human cancer cells
Authors: Monika Bug, Matthias Dobbelstein
Journal: Cancer Research (2009)

Abstract The tumor suppressor p53 plays a crucial role in our cells to induce cell cycle arrest or apoptosis in response to different kinds of genotoxic stresses. In 50% of all solid tumors, p53 is mutated by a single point mutation within the DNA-binding domain and thereby loses its activity as a tumor suppressor. However, at the same time, mutant p53 actively contributes to chemoresistance and tumor progression through a gain of function (Dittmer et al., 1993). It was previously shown that mutant p53 highly accumulates in tumors of mice with targeted germ line mutations of the p53 gene (knock-in), whereas normal cells of these mice express it at low levels (Lang et al., 2004; Terzian et al., 2008). This argues that the deregulation of tumor-specific signaling cascades leads to an accumulation of mutant p53 and subsequently to tumor progression. Our study aims at identifying these signaling pathways that contribute to the regulation of mutant p53 expression, and to describe their mechanisms. We performed quantitative analysis of mutant p53 protein levels in a cancer cell line after the individual knock-down of all known human kinases using automated microscopy (high content cell screening). The bladder carcinoma derived cell line 5637 (carrying the p53 R280T mutation) was transfected with three different synthetic siRNAs targeting each known kinase or kinase regulator in a 96-well format, and p53 was detected by automated immunofluorescence microscopy. In each of the resulting 2400 cell populations the p53 expression levels were determined for at least 500 individual cells. Alterations in the distribution of p53 staining intensities were assessed for each kinase relative to non-targeting control siRNAs. The results of the kinases, that lead to the strongest up- or down-regulations of mutant p53 in the screen, were confirmed in different cell lines (U251 and U373, both derived from glioma, with the p53 hot spot mutation R273H), by immunofluorescence and immunoblot analysis. We identified a group of kinases currently known to act in the PI3-kinase → mTOR pathway as potential regulators of mutant p53. The knock-down of these kinases resulted in a decrease of mutant p53 expression. Studying the mechanism of mutant p53 regulation, we performed quantitative real-time PCR after siRNA transfection and found no significant impairment of the p53 transcription. On the contrary, posttranslational modifications (phosphorylation and acetylation) of mutant p53 were decreased after knock-down of the identified kinases, even more strongly than the overall levels of the protein. These observations support the idea that the degradation of mutant p53 is decreased in cancer cells through alterations of PI3K-mTOR pathway associated kinases, resulting in p53 accumulation and oncogenic gain of function. Citation Information: Cancer Res 2009;69(23 Suppl):B54.
THU0260 Circulating levels of tnf-like cytokine 1A (TL1A) are increased in patients with ankylosing spondylitis
Authors: M. Konsta, M. Tektonidou, A. Iliopoulos, G. Bamias, P.P. Sfikakis
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> TL1A (TNFSF15) is a newly identified TNF-like cytokine that associates with the death domain receptor DR3 (TNFRSF25), expressed on activated lymphocytes. TL1A-DR3 binding produces costimulatory signals resulting in lymphocyte proliferation, secretion of pro-inflammatory cytokines and induction of apoptotic signals [1]. Recent studies have shown that both TL1A and DR3 are upregulated and possibly implicated in the pathogenesis of several chronic inflammatory conditions, including, inflammatory bowel disease, rheumatoid arthritis, and psoriasis [2, 3]. <h3>Objectives</h3> (a) To examine whether soluble TL1A is increased in Ankylosing Spondylitis (AS). (b) To search for possible correlations between TL1A serum concentration, and various clinical and laboratory parameters of AS. (c) To study the effect of anti-TNF treatment on soluble TL1A levels. <h3>Methods</h3> Seventy-five consecutive patients with AS (61 men), aged 47.2±15.5 years (mean±SD) with disease duration of 20.3±13.9 years, were included in this cross-sectional study. Nineteen age and sex-matched healthy individuals served as controls. Forty four patients were anti-TNF treatment-naïve, whereas the remaining patients were on infliximab (n=21), adalimumab (n=3), or etanercept (n=7). The patients' perceived disease activity and functional limitation were recorded by Bath AS Disease Index (BASDAI) and Bath AS Functional Index (BASFI) respectively. The objective functional status was evaluated by measurements of spinal mobility (AS-Metrology). Serum concentrations of TL1A were measured by ELISA. Mann-Whitney two-sample statistics was used for group comparisons and Spearman's coefficients for testing correlation between variables. <h3>Results</h3> Average serum concentration of TL1A were 3-fold higher in anti-TNF- naïve (601±1066 pg/ml) compared to anti-TNF-treated patients (196±302 pg/ml, p=0.018) and healthy controls (199±286 pg/ml, p=0.03). No significant association between individual TL1A serum levels and functional status (BASFI-score, AS metrology parameters), presence of extra-articular manifestations such as intestinal inflammation and uveitis, or C-reactive protein levels measured in the same individual was found. A positive correlation between individual serum levels of TL1A and BASDAI scores was noted (Spearman r=0.3, p=0.01). <h3>Conclusions</h3> We report increased serum concentrations of TL1A in AS which correlate with clinical disease activity and can be controlled by anti-TNF treatment. Interactions between TL1A and its receptors may be important in the pathogenesis of the disease. <h3>References</h3> Migone TS et al. Immunity 2002;16: 479-92. Bamias G et al. Clin Immunol 2008;129:249-55. Bamias G et al. Exp Dermatol 2011; 20:725-31. <h3>Disclosure of Interest</h3> None Declared