tbuckley/cabot-search huggingface dataset:
SP0147 Non-anti-TNF biologics in PSA
Authors: P. Mease
Journal: Annals of the Rheumatic Diseases (2013)

Despite the substantial benefit of TNFi therapy for psoriatic arthritis, as demonstrated in clinical trials and in over a decade of clinical use globally, there remains an unmet medical need for effective therapies for patients who do not benefit from TNFi initially, lose response over time, or have adverse effects, even with trials of multiple TNFi agents and traditional oral DMARDs. The definition of adequate response (low disease activity or remission) for PsA is evolving, as is the concept of treatment to target. The target of response in PsA is constituted by several clinical domains: arthritis, enthesitis, dactylitis, spondylitis, and dermatitis, all of which effect function and quality of life, and should be considered when determining a comprehensive treatment response. An understanding of the pathophysiology of the clinical domains of PsA provides a basis for selecting targets of therapy. Many of the pathophysiologic features of PsA overlap with those of rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriasis, and so it is natural to consider effective treatments for these conditions for the treatment of PsA. Preliminary evidence of the effectiveness of drugs with varying mechanism of action, shown to be effective in RA and/or psoriasis, exists or is being developed in PsA and will be reviewed. These include cellular modulators: co-stimulatory blockade agents which modulate T cell activity (abatacept and alefacept) and an agent which ablates B cells (rituximab). Several key pro-inflammatory cytokines other than TNF are being targeted, such as IL-12/23, IL-17, IL-6, and the multiple cytokines inhibited by the JAK inhibitors or the phosphodiesterase 4 (PDE4) inhibitor, apremilast, supported by data in RA, AS, and/or psoriasis. <h3>Disclosure of Interest</h3> None Declared
Abstract 3342: Tumor-initiating cells in human glioblastoma are heterogeneous populations which reside in distinct environmental niches
Authors: Sara Grazia Maria Piccirillo, Inma Spiteri, Andrea Sottoriva, Nicholas Marko, Simon Tavare', Peter Collins, Colin Watts
Journal: Cancer Research (2012)

Abstract We previously demonstrated that it is possible to objectively interrogate human glioblastoma (GBM) by using 5-aminolevulinic acid (5-ALA), an endogenous intermediate of the porphyrin biosynthesis pathway. It acts as a prodrug that is metabolised intracellularly leading to the selective accumulation of the fluorescent molecule protoporphyrin IX (PpIX) in tumor cells. Tumor tissue resection is then performed on a fluorescence-guided basis allowing direct visualization of tumor tissue and diffusely infiltrative disease. This approach gave us the possibility to identify and characterize tumor compartments in GBM. We have now interrogated tumor compartments based on PpIX fluorescence. Our results demonstrate that: 1) cells residing in the tumor margin do not resemble the “cancer stem cell” phenotype but are tumorigenic to some extent, 2) the margin tissue expresses markers of apoptosis, 3) fluorescence material is present in the SVZ of 65% of our GBM (n=65 patients) and it is possible to isolate TICs from these SVZs. These cells are phenotypically similar to those isolated from the tumor mass and possess all the “cancer stem cell” cardinal features, 4) SNP analysis of SVZ tissue samples reveals distinct genetic aberrations, 5) TICs in the SVZ reside in a pro-angiogenic environment. Further characterization of niches in tumor edges and SVZ as well as response to chemotherapeutic agents is in progress to highlight intra-tumoral heterogeneity of TICs. 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 3342. doi:1538-7445.AM2012-3342
Intravascular Small Cell Neuroendocrine Tumor in the Neck
Authors: Chian A. Chang, Ian Jong, Anna Nowicki, Shakher Ramdave
Journal: Clinical Nuclear Medicine (2014)

A 40-year-old man presented with a painless enlarging right neck mass over several weeks without a history of trauma or infection. Ultrasound, contrast-enhanced CT, and MRI showed a mass in an expanded vein extending into the parotid gland. Blood-stained fine-needle aspiration biopsy demonstrated atypical lymphoid cells, but there was insufficient material for a diagnosis. The mass was intensely avid on 18F-FDG PET/CT and was suggestive of a neoplasm. Excision confirmed a mass within the external jugular vein with areas of invasion through the vessel wall. A diagnosis of small cell neuroendocrine carcinoma was made on histology.
Abstract 535: Development of small-molecule hepsin inhibitors
Authors: Xi Tang, Valeri Vasioukhin
Journal: Cancer Research (2010)

Abstract Hepsin is a cell-surface serine protease prominently overexpressed in the majority of human prostate tumors. We and others have previously demonstrated that hepsin promotes prostate cancer progression and metastasis in vivo. These findings identified hepsin as a very attractive therapeutic target in prostate cancer. To develop small molecule hepsin inhibitors, we have previously performed in vitro screenings of libraries of small drug-like molecules. These efforts resulted in identification of several lead compounds inhibiting hepsin proteolytic activity. We now identified and performed additional characterization of the derivatives of most potent hepsin lead inhibitors. We also developed a novel cell-based hepsin activity assay, which utilizes expressed on the cell-surface human hepsin and C-terminally HA-tagged pro-HGF, as its specific cleavage substrate. Overall, this study identified specific and potent small-molecule hepsin inhibitors that may be potentially used in the future as therapeutic agents to attenuate prostate cancer progression in the ‘watchful waiting’ cohort of prostate cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 535.
The Effectiveness of a Regulatory Strategy in Containing Hospital Costs
Authors: Allan S. Detsky, Sidney R. Stacey, Claire Bombardier
Journal: New England Journal of Medicine (1983)

This study documents the increases in real inputs (e.g., labor and equipment) employed in Ontario's hospital sector between 1968 and 1981--a period of universal government-financed hospital insurance and a government regulatory strategy involving global budgeting. Total expenditures in Ontario increased by only 16 per cent in terms of real inputs, as compared with an increase of 101 per cent in the United States. Real inputs per patient-day increased at a mean annual rate of 0.68 per cent in Ontario versus 5.19 per cent in the United States (P less than 0.001). Real inputs per admission decreased at a mean annual rate of 1.12 per cent in Ontario, as compared with an increase of 4.15 per cent in the United States (P less than 0.0001). We conclude that regulation can contain the growth of real inputs employed in the hospital sector even in the face of an incentive structure that does not promote cost consciousness on the part of patients or physicians. Although the effect of this strategy on the quality of care is unknown, so far it appears to have been politically acceptable in Ontario.
Induction of Renal Tumors in Cynomolgus Monkeys (Macaca fascicularis) by Prenatal Exposure to 1,2-Dimethylhydrazine
Authors: D. Sh. Beniashvili
Journal: JNCI Journal of the National Cancer Institute (1989)

Nephroblastomas were induced at an early age in two of six cynomolgus monkeys by prenatal exposure to 1,2-dimethylhydrazine. In one, the tumor of the right kidney had metastasized into the lower lobes of the lungs. By their histologic structure, development, and clinical course, the induced nephroblastomas were analogous to the Wilms' tumors often found in children.
A Study of Virus Carriers from a Poliomyelitis Outbreak at a Boys' Camp
Authors: A. Daniel Rubenstein, J. Pervis Milnor, Herdis von Magnus, Joseph L. Melnick
Journal: New England Journal of Medicine (1948)

SMALL, localized outbreaks of poliomyelitis offer unusual opportunities for epidemiologic study. The more isolated the population unit under observation, the less complex appears the task of tracing chains of infection. However, it remains for future discoveries to determine how true this may actually be so far as poliomyelitis is concerned.A recent outbreak of poliomyelitis in a boy-scout camp in western Massachusetts seemed to be particularly well suited for epidemiologic study. In the first place, prior to its occurrence, no cases of infantile paralysis had been reported from all of western Massachusetts for three months. Furthermore, the location of the . . .
Idarubicin improves blast cell clearance during induction therapy in children with AML: results of study AML-BFM 93
Authors: U Creutzig, J Ritter, M Zimmermann, J Hermann, H Gadner, D Blütters Sawatzki, CM Niemeyer, D Schwabe, B Selle, J Boos, J Kühl, A Feldges
Journal: Leukemia (2001)
AB0503 A comparative study of early clinical efficacy among three anti-TNF agents – drag race study
Authors: Y. Hirano, Y. Oishi, K. Yamauchi, T. Mieno
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Anti-tumor necrosis factor (TNF) therapy is recommended when conventional DMARDs therapy fails to decrease disease activity of rheumatoid arthritis (RA) to at least low disease activity. One of the advantages in anti-TNF therapy is its rapid response in comparison to conventional DMARDs therapy. Although several anti-TNF agents are available in clinical setting, the information on the difference in rapidness of early response among different anti-TNF agents is lacking. <h3>Objectives</h3> The objectives of this retrospective study is to compare early clinical efficacy among three anti-TNF agents, namely infliximab (IFX), etanercept (ETN) and adalimumab (ADA), in RA patients. This study is called "Drag Race Study". <h3>Methods</h3> Bio-naive RA patients treated with one of three anti-TNF agents with concomitant MTX were included in this Drag Race Study. Clinical data at initiation and at 6 weeks in IFX-group (n=64) and clinical data at in initiation and at 4 weeks in ETN-group (n=43) and ADA-group (n=24) were used. IFX was infused in the dosage of 3mg/kg at 0w, 2w and 6w. ETN was subcutaneously injected in the dosage of 50mg/w or 25mg/w. ADA was subcutaneously injected at the dosage of 40mg per every other week. Improvement rate (%) and improvement value (Delta) of 6 indices (DAS28-ESR, DAS28-CRP, VAS, CRP, ESR, MMP-3, mHAQ) were compared between groups. Comparison between ETN25mg/w-group and ETN 50mg/w-group was also performed. <h3>Results</h3> Mean age (years old) in IFX-G, ETN-G and ADA-G was 54, 58 and 58, respectively. Mean RA duration (years) in IFX-G, ETN-G and ADA-G was 9.8, 9.6 and 9.6, respectively. The baseline characteristics of patients and the baseline disease activity were comparable among there groups. Results were shown in the table. No significant difference was observed between groups. There was no significant difference in early clinical efficacy between ETN25mg/w-G and ETN50mg/w-G. <h3>Conclusions</h3> This study showed that all of three anti-TNF agents had early excellent clinical efficacy in same extent and that early efficacy in ETN25mg/w-G was comparable to that in ETN50mg/w-G. This study suggests that rapid step-up in the treatment, for example dose escalation of biological agents or concomitant DMARDs, may be necessary when early effects of anti-TNF therapy are not excellent. <h3>Disclosure of Interest</h3> None Declared
Use of the Tank Respirator in Overwhelming Bacterial Pneumonia
Authors: Frank L. Miller, Alfonso Zerbi-Ortiz, John T. Elkins
Journal: New England Journal of Medicine (1960)

WHEN conventional forms of treatment have proved ineffective in an illness that is rapidly progressing toward death, a successful outcome with an unconventional form of treatment is most unusual. The patient described below, who had overwhelming staphylococcal pneumonia, was moribund when placed in an Emerson tank respirator. All conventional forms of therapy had been tried and had failed. We believe that the successful use of this form of mechanical ventilation for primary bacterial pneumonia is without precedent and is worthy of report.Case ReportA 37-year-old Negro incurred an abdominal injury in an automobile accident on October 21, 1958. This . . .
Initial Experience Using 99mTc-MIBI SPECT/CT for the Differentiation of Oncocytoma From Renal Cell Carcinoma
Authors: Steven P Rowe, Michael A Gorin, Jennifer Gordetsky, Mark W Ball, Phillip M Pierorazio, Takahiro Higuchi, Jonathan I Epstein, Mohamad E Allaf, Mehrbod S Javadi
Journal: Clinical Nuclear Medicine (2015)

Purpose The differentiation of oncocytoma from renal cell carcinoma (RCC) remains a challenge with currently available cross-sectional imaging techniques. As a result, a large number of patients harboring a benign oncocytoma undergo unnecessary surgical resection. In this study, we explored the utility of 99mTc-MIBI SPECT/CT for the differentiation of these tumors based on the hypothesis that the large number of mitochondria in oncocytomas would lead to increased 99mTc-MIBI uptake. Patients and Methods In total, 6 patients (3 with oncocytoma and 3 with RCC) were imaged with 99mTc-MIBI SPECT/CT. Relative quantification was performed by measuring tumor-to-normal renal parenchyma background ratios. Results All 3 oncocytomas demonstrated radiotracer uptake near or above the normal renal parenchymal uptake (range of uptake ratios, 0.85–1.78). In contrast, the 3 RCCs were profoundly photopenic relative to renal background (range of uptake ratios, 0.21–0.31). Conclusions 99mTc-MIBI SPECT/CT appears to be of value in scintigraphically distinguishing benign renal oncocytoma from RCC.
Case 18-1988
Authors: Richard C. Cabot, Robert E. Scully, Eugene J. Mark, William F. McNeely, Betty U. McNeely, Stephen C. Schoenbaum, Richard L. Kradin
Journal: New England Journal of Medicine (1988)

Presentation of CaseA 30-year-old man was admitted to the hospital because of cough, dyspnea, and weight loss.He was well until three weeks earlier, when he had a brief illness characterized by fever and malaise; the illness was followed by increasing malaise and marked fatigue. Two weeks before admission the patient became bedridden because of severe weakness. Dyspnea appeared and worsened progressively. During the week before entry a cough developed and was productive of thick yellow to brown sputum, with myalgia and diarrhea. He was admitted to the hospital.The patient was single and lived alone. He worked as . . .
Abstract 901: Overexpression of inhibitors of apoptosis (IAP) family members in human breast and ovarian cancer models of non-<i>MDR1</i> taxane resistance.
Authors: George E. Duran, Anamaria Brozovic, Francisco J. Martinez, E Brian Francisco, Yan C. Wang, Branimir I. Sikic
Journal: Cancer Research (2013)

Abstract Four breast cancer cell lines (MCF-7, BT-549, MDA-MB-231 and T-47D) and four ovarian cancer cell lines (1A9/A2780, ES-2, MES-OV and OVCAR-3) were selected for taxane resistance by exposing cells to either docetaxel or paclitaxel in the presence of the P-glycoprotein inhibitor, PSC-833 (valspodar, 2 μM). All of these co-selected variants are MDR1/ABCB1(-), and the resistance to taxanes is not transporter-mediated. We have previously reported elevated class III β-tubulin (TUBB3), reduced BRCA1, elevated CDKN1A (p21), and altered epithelial-mesenchymal transition (EMT) genes in the majority of the non-MDR1 taxane variants. Inhibitors of apoptosis (IAP) proteins directly bind and inhibit several caspases, and may play a critical role in determining cell fate after exposure to chemotherapeutic agents. In this study, we profiled the expression of IAP proteins and found elevated content in this panel of taxane-resistant human breast and ovarian cancer cell lines. In both the paclitaxel- (TP) and docetaxel-selected (TxTP) ovarian cancer cell lines we observed significantly overexpressed cIAP1 (BIRC2), cIAP2 (BIRC3), XIAP (BIRC4), and Livin (BIRC7) relative to parental cell lines. Expression of cIAP2 was undetectable in OVCAR-3 and its taxane resistant cell lines, OVCAR-3/TP20 and OVCAR-3/TxTP5. Elevated cIAP1 and XIAP levels were detected in the human breast cancer variant BT-549/TxTP50, and Livin was overexpressed in all taxane-resistant breast cancer cell models. Survivin (BIRC5) is highly expressed in cancers and has been associated with taxane resistance via its effects on apoptosis and the cell cycle. We observed reduced Survivin content in the majority of the variants established in our laboratory except for the ovarian ES-2/TP80 cell line where we found slightly elevated expression resulting from paclitaxel selection relative to its parental control. In addition to these alterations in IAP content, we observed elevated Bcl-2 in ovarian (MES-OV/TP40 and MES-OV/TxTP50) and breast (MCF-7/TxTP50, BT-549/TxTP50, and MDA231/TxTP50) cancer cell lines at the transcript level by rt-PCR and confirmed by immunoblotting. Specific gene silencing by RNAi and treatment with small molecule inhibitors will test the functional significance of IAP alterations in these models of taxane resistance. Citation Format: George E. Duran, Anamaria Brozovic, Francisco J. Martinez, E Brian Francisco, Yan C. Wang, Branimir I. Sikic. Overexpression of inhibitors of apoptosis (IAP) family members in human breast and ovarian cancer models of non-MDR1 taxane resistance. [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 901. doi:10.1158/1538-7445.AM2013-901
Gossypiboma successfully removed by endoscopy after endoscopic ultrasound-guided transmural drainage
Authors: K. Matsumoto, A. Katanuma, H. Maguchi, K. Takahashi, M. Osanai, K. Yane, T. Kin, R. Takaki, T. Matsumori, K. Gon, A. Tomonari
Journal: Endoscopy (2013)

Endoscopy is an emerging diagnostic as well as treatment modality for gossypiboma [1] [2] [3] [4] [5]. Here we report successful endoscopic removal of a gossypiboma after endoscopic ultrasound (EUS)-guided transmural drainage.
Successful Management of Massive Small-Bowel Resection Based on Assessment of Absorption Defects and Nutritional Needs
Authors: S. J. Winawer, S. A. Broitman, D. A. Wolochow, M. P. Osborne, N. Zamcheck
Journal: New England Journal of Medicine (1966)

MASSIVE resection of more than two thirds of the small intestine is a clinical catastrophe.1 , 2 Although earlier studies were concerned mostly with survival statistics3 more recent studies have emphasized an evaluation of the absorptive potential of the remaining gut as a guide to treatment.4 5 6 7 8 9 10 11 12 13 The present study reports the successful management, nutritional requirements and absorptive capacity in a seventeen-year-old boy who has to date survived for more than two years since massive resection of the small bowel. His remaining small intestine consists of duodenum, 13 cm. of proximal jejunum and 5 cm. of terminal ileum. The ileocecal valve and colon . . .
P4-10-10: Breast Cancer Risk Factors among Asian Versus Caucasian Women with BRCA1/2 Mutations.
Authors: Bruin MA de, A Kwong, BA Goldstein, JA Lipson, DM Ikeda, LA McPherson, B Sharma, A Kardashian, EA Schackmann, KE Kingham, MA Mills, DW West, JM Ford, AW Kurian
Journal: Cancer Research (2011)

Abstract Background Prior research suggests that the prevalence and penetrance of BRCA1/2 mutations may be different in Asians compared with Caucasians. Such differences in penetrance could be related to genetic, as well as hormonal, reproductive and lifestyle factors. Methods: Chinese and Caucasian BRCA1/2 mutation carriers were recruited from genetics clinics in Hong Kong and California. We compared personal and family history of cancer, as well as hormonal, reproductive and lifestyle exposures between racial groups. Breast density was estimated using BIRADS breast composition categories on mammogram. We analyzed DNA samples for single-nucleotide polymorphisms (SNPs) that may modify BRCA-associated cancer risk, and compared the prevalence between groups. A multivariable analysis of potential modifiers of cancer risk is underway. Results: Forty-two Chinese women from Hong Kong and forty-nine Caucasian women from California were enrolled. BRCA1 mutations were more common in Caucasian women (63% vs. 43%, P=0.05), while BRCA2 mutations were more common among Chinese women (57% vs. 33%, P=0.02). More Chinese women had a personal history of breast cancer (91% vs. 53%) and ovarian cancer (12% vs. 4%). In contrast, significantly more Caucasian women had a family history of breast and ovarian cancer. On average, Caucasian women had higher parity, breastfed more, had less dense breasts on mammogram, and more often underwent prophylactic oophorectomy, all of which are protective against breast cancer in the general population. However, Caucasian women also consumed more alcohol and had higher average BMI. Risk associated alleles in RAD51, MAP3K1 and TOX3/TNRC9 were more common in Chinese women; risk associated alleles in FGFR2 and RASSF1 were similar in frequency between groups. Results of the multivariable analysis are pending and will be presented. Discussion: We found notable differences between Chinese and Caucasian women in the proportion of BRCA1 versus BRCA2 mutations, and in the distribution of hormonal, reproductive and lifestyle factors, and SNPs associated with breast cancer risk. Such variations in risk-modifying factors may contribute to differences in BRCA mutation penetrance. Enhanced understanding of racial differences in BRCA1/2 mutation epidemiology may inform targeted cancer screening and prevention strategies. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-10-10.