tbuckley/cabot-search huggingface dataset:
P5-01-07: Identification of SORBS2 as a Candidate Marker To Predict Metastatic Relapse in Breast Cancer.
Authors: S Alsafadi, V Scott, P Pautier, A Goubar, V Lazar, P Dessen, L Lacroix, P Duvillard, P Morice, F André, S Delaloge
Journal: Cancer Research (2011)

Abstract Background Elucidation of promising cancer biomarkers from gene expression data can provide important insight into the relationship between signaling networks and cancer. SORBS2, sorbin and SH3 domain containing 2, is a multi-adapter protein involved in signal transduction associated to the cytoskeleton and was reported to be strongly repressed in pancreatic and cervical cancers. Methods: With the purpose of identifying genes involved in metastatic process, we compared gene expression profiling of 19 invasive ovarian cancers and 24 borderline tumors. Prognostic value of the selected genes was then tested in a gene expression array database that includes 1659 patients with early breast cancer (Gyorffy B et al. 2010). Upon isolation of SORBS2 as a predictor, its involvement in cell migration and tumor progression was investigated in vitro. Small interfering RNA targeting SORBS2 was used to downregulate its expression in T47D and Hela, two cell lines overexpressing SORBS2. Functional effect of siRNA-induced knockdown of SORBS2 on cell viability was determined by WST-1 assay and Trypan Blue exclusion test. Effect on cell migration was evaluated by wound-healing and transwell assays. Western blot analyses were also performed to examine the expressions of proteins involved in cell survival, death and migration. Results: High-throughput analyses of genes that are differentially expressed between borderline ovarian tumors and invasive carcinoma demonstrated that SORBS2 is significantly downregulated in invasive carcinoma (FDR&amp;lt;10e-10). Moreover, SORBS2 loss was a strong predictor of relapse in a gene expression array dataset of 1659 patients presenting an early breast cancer (HR=0.62, 0.52−0.72, p=6.4e-10). In vitro studies showed that SORBS2 specific downregulation stimulated cell proliferation, by an average of 40%, in T47D and Hela cell lines. SORBS2 knockdown had no effect on either cell migration rate or protein expressions of p-FAK and p-Paxillin, two focal adhesion proteins which are critical to cell adhesion and migration. No significant variations in protein expressions of Akt/mTOR pro-survival or caspases activation pathways were observed. Gene expression profiling before and after SORBS2 dowregulation is ongoing in the two cell lines. Conclusion: This study is the first to provide evidence for an antiproliferative activity of SORBS2 with no effect on cell migration in breast cancer cells. Our clinical and in vitro data suggest that SORBS2 is a candidate marker to predict relapse in patients with early breast cancer. Molecular mechanisms mediating the antiproliferative effect of SORBS2 are currently being investigated. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-01-07.
Case 34-2015
Authors: Arezou Khosroshahi, Subba R. Digumarthy, Fiona K. Gibbons, Vikram Deshpande
Journal: New England Journal of Medicine (2015)

A 36-year-old woman presented with a mass in the middle lobe of the right lung. Lobectomy was performed, and examination of the specimens revealed evidence of lipoid pneumonia and fibrinous pleuritis. Six months later, pain in the right hip developed. A diagnosis was made.
Estimating future health spending by source in 184 countries, 2013–2040
Authors: Tara Templin, Nafis Sadat, Abby Chapin, Joseph L Dieleman
Journal: The Lancet Global Health (2016)

Background There is great variation in annual health spending between countries, and differences in how this spending is financed. For example, the average annual spend on health care in low-income countries in sub-Saharan Africa in 2013 was $135 per person (in 2010 purchasing-power-parity dollars), whereas in high-income countries it is up to 22 times larger. Future health spending estimates and information about the expected source of those funds are hugely important for successful short-term and medium-term planning, maintaining fiscal sustainability, and addressing critical funding gaps. We aimed to forecast government health spending, out-of-pocket health spending, pre-paid health insurance spending, and development assistant for health in 184 countries from 2013 to 2040.
Phase I trial of erlotinib (E), modified FOLFOX6 (mFOLFOX6), and bevacizumab (B) as first-line therapy for metastatic colorectal cancer (MCRC)
Authors: D. Singh, L. Rath, J. A. Bokar, J. M. Brell, M. M. Cooney, A. Dowlati, J. Gibbons, C. J. Nock, P. Savvides, S. S. Krishnamurthi
Journal: Journal of Clinical Oncology (2008)

15076 Background: Pre-clinical and clinical data suggest epidermal growth factor receptor (EGFR)-inhibition may augment the activity of FOLFOX as treatment of MCRC. The severity of rash induced by EGFR-inhibitors correlates with response rate (RR) and survival. This phase I study of mFOLFOX6 and B plus the EGFR tyrosine kinase-inhibitor E, includes escalation of the E dose for patients (pts) without grade 2 E-related toxicities. Methods: The study endpoints are to evaluate the safety and efficacy of E + mFOLFOX6 + B and the feasibility of escalation of E dose above 150 mg daily. Enrollment of 20 evaluable pts is planned. Eligibility requirements: no prior chemotherapy or B for metastatic disease, no prior EGFR-inhibitor therapy, adequate organ function. Each cycle is 14 days. E 150 mg is administered daily and as a single agent in cycle 1. mFOLFOX6 (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, 5-FU bolus 400 mg/m2, and 46-hour continuous infusion 5-FU 2.4 g/m2) is added at cycle 2 and B (5mg/kg) is added at cycle 3; both are administered every 14 days. Pts without grade 2 E-related toxicity during the first 3 cycles have E increased to 200 mg daily. Pts are monitored for DLT during the first 3 cycles. DLT in 2 of the first 6 pts, 3 of the first 9 pts, or 4 of the first 12 pts will require that subsequent pts enrolled receive 100 mg E daily. Results: 10 pts have enrolled and thus far 8 are evaluable for toxicity and response. No patient met criteria for E dose escalation. Two pts experienced DLT of grade 3 rash. Other grade 3 toxicity within cycles 1–3 were vomiting (1 patient) and diarrhea (1 patient), neither optimally treated and therefore not DLT, and grade 3 ANC (2 pts). E was decreased to 100 mg in 3 pts after cycle 3 due to grade 3 diarrhea. Four pts had a partial response, 3 had stable disease, and 1 had disease progression. Enrollment is ongoing at the 150 mg E dose. Conclusions: This regimen of single agent E 150 mg daily for 14 days with sequential addition of mFOLFOX6 and 5 mg/kg B has had acceptable toxicity to date. Escalation of the E dose beyond 150 mg has not been possible. Supported by U01 CA062502–12. E provided by Genentech. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Genentech™ BioOncology Genentech™ BioOncology
Abstract 2084: Claudin-1 induces resistance to anoikis in Src dependent manner in colon cancer cells
Authors: Ashok Sharma, Amar B. Singh, Joshua J. Smith, Chen Xi, Robert D. Beauchamp, Punita Dhawan
Journal: Cancer Research (2012)

Abstract Anoikis, a complete loss of cell anchorage triggers apoptosis in primary human colonic epithelial cells (CEC), is often dysfunctional in metastatic cancer cells. We along with other groups have demonstrated that expression of Claudin-1, a tight junction protein, is markedly increased and mislocalized in colon cancer and helps promote the tumor progression especially metastasis. However the underlying mechanism remains poorly understood. To explore, we examined effect of claudin-1 expression upon anoikis. Colon cancer cells genetically manipulated (stable overexpression in SW480 cells and RNA-interference based gene silencing in SW620 cells) for claudin-1 expression were cultured on polyHEMA-coated culture dishes to induce anoikis. Results demonstrated a positive correlation between claudin-1 expression and resistance to anoikis. We also observed a positive correlation between claudin-1 expression, Src (L4A1) and Akt phosphorylation (Ser 473) and Bcl-2 expression in the cells subjected to anoikis. Notably, use of PP2, a Src-kinase inhibitor, inhibited claudin-1-dependent resistance to anoikis (2.5fold) as well as the increases in Akt-phosphorylation and Bcl-2 expression, and thus suggested a causal role of Src-activation in claudin-1-dependent resistance to anoikis. Our further studies revealed that claudin-1 associates with Src in a multi-protein complex that also included ZO-1, a PDZ-domain containing tight junction protein, known to associate with claudin-1and Src. Importantly, claudin-1 contains a PDZ-binding domain in its c-terminal. Deletion of the c-terminal domain of claudin-1 resulted in the loss of the physical association between claudin-1 and Src and a significant loss in claudin-1-dependent resistance to anoikis. Thus, our findings supported a role of claudin-1 in the regulation of colon cancer progression through its association with Src and dependent cell signaling. Our further analysis using a large database of colon cancer patient samples (microarray analysis; 260 colon cancer and 10 adjacent normal colon samples) showed a significant and positive correlation between claudin-1 and Src expression. Taken together, we here report a novel partnering between claudin-1 and Src proteins in colon cancer cells which has a function implication in the regulation of anoikis in a claudin-1/Src/PI3-kinase/Bcl-2-dependent manner. Our findings have clinical significance and have the potential to open potential new therapeutic opportunity in colon cancer treatment and/or management. 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 2084. doi:1538-7445.AM2012-2084
Infantile Hemangioendothelioma of the Liver, Spleen, and Anterior Abdominal Wall
Authors: RAKESH KUMAR, RITESH GUPTA, BHARATHI DASAN J, SHIKHA KHULLAR, ATUL MARWAH
Journal: Clinical Nuclear Medicine (2000)

Infantile hemangioendotheliomas are benign vascular tumors involving the liver, but it can also involve the spleen and other organs. Although benign, they are generally detected during infancy because shunting often results in high-output cardiac failure. The authors describe a 6-month-old infant with breathlessness, difficulty in breast-feeding, and abdominal distention that began at 3 months. Examination revealed tachypnea, tachycardia, gross hepatosplenomegaly, and bilateral crepitations. Ultrasound showed discrete hypoechoic lesions of the liver, spleen, and the anterior abdominal wall suggestive of multiple hemangiomas. Tc-99m phytate and Tc-99m RBC blood-pool imaging confirmed the diagnosis of multiple hemangiomas involving the liver, spleen, and the anterior abdominal wall.
Abstract 4241: Flavokawain B, a kava chalcone, induces apoptosis in synovial sarcoma cell lines
Authors: Toshinori Sakai, Yi Guo, Eskander Ramez, Jason Mefford, Justin Hopkins, Xiaolin Zi, Nitin N. Bhatia, Bang H. Hoang
Journal: Cancer Research (2011)

Abstract Synovial sarcoma (SS) is a soft tissue sarcoma with poor prognosis and lack of response to conventional cytotoxic chemotherapy. The regulatory mechanisms for the rapid proliferation of synovial sarcoma poorly understood. Surgical resection with/without adjuvant radiotherapy and chemotherapy are the mainstay of treatment. Although the sarcoma cell lines have moderate chemosensitivity to isofamide and doxorubicin therapy, the overall prognosis is still poor. Therefore, further development of the treatment for SS is required. Kava is an ancient crop of the western Pacific. The root extract of kava has been served as a traditional beverage for Pacific Islanders. Consumption of this traditional beverage has been thought to be correlated with low and uncustomary sex ratios of cancer incidence in 3 kava-drinking countrites: Fiji, Vanuatu and Western Samoa. We have already reported that a kind of fravokawains from kava extracts (FKA: flavokawein A) induced apoptosis against bladder cancer cells, and flavokawein B (FKB) was also significant effective in inhibiting the growth of prostate cancer cells. In this study, we examined the inhibitory proliferation effects of the FKB in synovial sarcoma growth and whether FKB modulates tumor apoptosis cascades in human synovial sarcoma cell lines. We treated 2 cell lines of synovial sarcoma (SYO-I, HS-SY-II) by different concentrations of FKB (0, 2.5, 5.0, 7.5 μg/μl) for 24 hours. From the results of real time PCR, depending on the concentrations of FKB in both cell lines, the expression of Survivin was found to be decreased, while those of DR5, Puma, and Bim were increased. These results indicated that FKB effectively induces apoptosis of the two cell lines depending on the concentration. In conclusion, our findings demonstrate that FKB is effective for growth inhibition of synovial sarcoma cell lines in vitro and suggest that FKB may be a new therapeutic option for patients with synovial sarcoma. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4241. doi:10.1158/1538-7445.AM2011-4241
Abstract 4065: Suppression of mannosylphospho dolichol synthase (DPMS) expression by vector-based siRNA technology reduces angiogenesis and inhibits tumor growth
Authors: Zhenbo Zhang, Aditi Banerjee, Jesus Santiago, Krishna Baksi, Dipak K. Banerjee
Journal: Cancer Research (2010)

Abstract Suppression of mannosylphospho dolichol synthase (DPMS) expression by vector-based siRNA technology reduces angiogenesis and inhibits tumor growth Zhenbo Zhang1, Aditi Banerjee1, Jesus Santiago1, Krishna Baksi2 and Dipak K. Banerjee1. 1Dept Biochem, Sch Med, Univ Puerto Rico, San Juan, PR and Dept Anatomy and Cell Biol, Sch Med, Universidad Central del Caribe, Bayamon, PR, USA. Mannosylphospho dolichol synthase (DPMS), a 31kDa phosphoprotein is essential for the synthesis of lipid-linked oligosaccharide (LLO; Glc3Man9GlcNAc2-PP-Dol), a pre-requisite for asparagine-linked (N-linked) protein glycosylation. Earlier observations from our laboratory have suggested that up-regulation of DPMS activity plays an important role in capillary endothelial cell proliferation and consequently in angiogenesis. Our recent study suggests that blockade of N-linked glycosylation by tunicamycin may provide a novel therapeutic approach for the treatment of cancers. However, the roles of suppressing DPMS expression by genetic manipulation and its impact on angiogenesis and tumor cell proliferation have not been investigated. We report here that knocking down DPMS expression by vector-based short interfering RNA technique dramatically reduced the N-linked glycosylation of protein in endothelial cells and inhibited angiogenesis and cell proliferation. After isolating DPMS overexpression and siRNA stable cell lines, DPMS expression in these cells has been confirmed by fluorescence microscopy, western blotting, QRT-PCR and measuring the catalytic activity. All detected elevated DPMS level in overexpressing clone but is down-regulated in cells silenced with siRNA. Fluorescence microscopy with WGA supported high expression of complex glycans on the cell surface overexpressing DPMS and is considerably reduced in cells DPMS silenced with siRNA. Two-dimension gel combined fluorescence with FITC-labeled Con A and Texas-Labeled WGA also support this observation. Overexpressing DPMS clone proliferates faster compared to the cells whose DPMS has been silenced with siRNA. This is corroborated with the cell proliferative antigens Bcl-2 and PCNA expression monitored by western blotting and/or by QRT-PCR. In wound healing assay DPMS overexpression facilitated faster cell migration than its siRNA clone. Thus, DPMS exerts influence on capillary endothelial cell proliferation and may serve as a modulator of angiogenesis. We, therefore, conclude that DPMS may serve as a potential target for developing anti-angiogenic therapeutics treating cancer. Supported by Susan G. Komen for the Cure BCTR 056206 (DKB) and NIH/NCRR/RCMI G12-RR0303 (KB) grants. 1 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 4065.
FRI0276 Alpha-melanocyte stimulating hormone analogue: beneficial effect in murine lupus activity
Authors: D. Botte, I. Noronha, D. Malheiros, S. Mello
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> Alpha-Melanocyte stimulating hormone (α-MSH) is a neuropeptide that plays antiinflamatory activity through the modulation of key molecules involved in the immune response. There is no data about their role in Systemic lupus erythematosus (SLE). <h3>Objectives</h3> The aim of the present study was to evaluate the anti-inflammatory efficacy of α-MSH in pristane-induced mice model of lupus. <h3>Methods</h3> Lupus-like model was induced in Balb/cAn mices by a intraperitoneal injection of a single dose of 500 μl of pristane oil. After SLE induction, animals were daily treated with the MSH analog (Nle4, DPhe7-α-MSH, 1.25 mg/Kg/day ip.) or saline 0.9%. After 6 month of SLE induction animals were sacrificed and the evaluated parameters of disease were: serum IgG isotypes (ELISA), antinuclear antibodies (ANA, in Hep-2 cells). The severity of arthritis was graded by assessing the level of swelling in each paw (0.5 = swelling of toes only or very slight ankle/wrist swelling; 1 = slight swelling of paw; 2 = moderate swelling of paw; 3 = marked swelling of paw; and 4 = substantial swelling of paw). Renal lesions were evaluated in 3 m paraffin sections stained with periodic acid Schiff (PAS) and hematoxylin and eosin (H&amp;E). Sections were graded as follows: 1 = mild focal mesangial hypercellularity alone; 2 = moderate mesangial hypercellularity; 3 = complex endocapillary hypercellularity with mild sclerosis or necrosis; 4 = severe endocapillary proliferative glomerulonephritis with necrosis/crescent formation. <h3>Results</h3> SLE animals presented increase in seric IgG1, 2a, 2b and 3 subtypes and ANA positivity. Arthritis and renal lesion score were increased when compared with normal animals (table). The treatment of SLE animal with α-MSH promoted a significant reduction of seric IgG subtypes, as well as in the number of animals with ANA positivity. The arthritis score was 70% reduced. SLE animals treated with α-MSH shows a reduction of 20% of glomerulus cellularity and 50% of reduction of renal lesion (table). <h3>Conclusions</h3> Our results suggest, for the first time, that the use of the α-MSH analog ameliorates the disease activity in an experimental model of lupus and seems to be a promising drug for treating SLE. <h3>Acknowledgements</h3> # Supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) <b>Disclosure of Interest</b>: None Declared
Linear X-Ray Shadows in Acquired Pulmonary Hemosiderosis and Congestion
Authors: Felix G. Fleischner, Leopold Reiner
Journal: New England Journal of Medicine (1954)

FAINT horizontal linear shadows are often observed in the lower lateral fields of the lung on roentgenograms of patients suffering from either acute or chronic recurrent pulmonary congestion, particularly in severe mitral stenosis. We have seen identical lines in pulmonary hemosiderosis in the absence of acute pulmonary congestion. This observation has not previously been recorded, either in the original descriptions of the latter condition by Rosenhagen1 and Zdansky2 or in the more recent comprehensive reviews by Scott et al.3 and Pendergrass and his co-workers.4 These linear shadows are usually best seen just above the costophrenic angle along the lateral chest . . .
Abstract C67: Gene expression profiling with human breast cancer cell lines exposed to gephyronic acid
Authors: Jeanette Young, Amy Leliaert, Zachary T. Schafer, Richard E. Taylor
Journal: Cancer Research (2011)

Abstract Gephyronic acid is an antibiotic natural product isolated at the HZI (Helmholtz-Zentrum für Infektionsforschung) by Sasse and Höfle from the myxobacterium Archangium gephyra in 1995. Gephyronic acid has been shown to inhibit the growth of yeast and mold in the micromolar range; it also exhibits a cytostatic effect on mammalian cell cultures (human cervix, human leukemia, hamster kidney, hamster ovary, mouse connective tissue, and monkey kidney cancer cells) in the nanomolar range. An in vitro translation assay demonstrated that gephyronic acid is a specific inhibitor of eukaryotic protein synthesis. Interdisciplinary efforts within our laboratory are directed to the evaluation of gephyronic acid as a potential anticancer agent and its structural and biological relationship to the myriaporones and tedanolides. Our recent structural assignment and total synthesis of gephyronic acid incorporates a synthetic route that provides a means by which to access significant quantities of gephyronic acid efficiently and selectively, thus facilitating further biological evaluation. Additionally, we seek to identify the mode of action for gephyronic acid by screening various cancer cell lines through transcriptome and proteome profiling. Our proposed method will analyze mRNA expression levels of cells treated with gephyronic acid, or without for control, through the application of cDNA microarrays. Transcript profiling will then be coupled to proteomic profiling utilizing a method of protein labeling called iTRAQ. Identifying specific genes and their associated proteins will secure the mode of action of gephyronic acid selective activity and further defines potential as a chemotherapeutic lead. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr C67.