tbuckley/cabot-search huggingface dataset:
Dissecting the invasive potential of esophageal cancer by siRNA library screening.
Authors: Shane P Duggan, Sinead Phipps, Fiona Behan, Catherine Garry, Dermot P Kelleher
Journal: Journal of Clinical Oncology (2015)

86 Background: The low survival for esophageal cancer is in part attributed to its high invasive potential and distant metastasis. In cancer, abnormal cell migration is an essential component of metastasis, and it is reasonable to consider that the conversion between different forms of morphology permits tumor cells to metastasise. Discovering regulators of esophageal cancer morphogenesis may aid in the development of novel targeted therapies that limit metastatic potential. Methods: GOhTRT cells were seeded and treated with siRNA (Human Druggable Genome, Dharmacon) by reverse transfection. Cells were fixed, immunostained for DNA, tubulin and actin and imaged with automated microscope. Cell images were processed using the InCell Analyzer software and the R statistical software systems CellHTS2 and RNAither. The effect of RNAi knockdown on cell viability and cell motility were assessed using MTT cell proliferation assay and scratch wound assay. Results: 127 gene candidates greatly exhibited effects on F-actin and α-tubulin area staining. This list was refined to six high quality candidates (RRM2, ITGB8, GPS1, SPRY1, NOL1 and MYO9B). Silencing of GPS1, MYO9B and SPRY1 increased the rate of migration in a scratch wound assay, with 86.98% ± 3.097%, 75.78% ±5.454% and 72.97% ± 5.463% (p =0.0022) respectively. There was no significant difference in cell viability absorbance values for siGPS1 (0.9037 ± 0.06575; p =0.1905) and siSPRY1 (0.9088 ± 0.09849; p =0.2985), which suggests that the increased rate of wound closure previously seen is by virtue of migratory signalling as oppose to an increase in cell proliferation. Cell viability was decreased considerably in siRRM2 cells (0.2492 ± 0.02798; p &lt;0.0001) and siMYO9B (0.4048 ± 0.04663; p&lt;0.0001) in comparison to siNT cells (1.046 ± 0.07712). Conclusions: In summary, this screen successfully identified high confidence hits associated with cytoskeletal remodelling, some of which are already associated with metastasis in literature and database searches. Further mechanistic studies and gene pathway analysis of candidate genes will provide novel therapeutic targets which can be utilised to block the spread of cancer in patients.
Abstract 17512: Importance of Pain-to-Door Time and Door-to-Balloon Time in Treating ST-Elevation Myocardial Infarction
Authors: Dong-Ho Shin, Yongsung Suh, Erdembileg Dander, Jung-Sun Kim, Byeong-Keuk Kim, Young-Guk Ko, Donghoon Choi, Hyun-Ah Ahn, Sun-Ho Joung, Young Mi Park, Myeong-Ki Hong, Namsik Chung, Yangsoo Jang
Journal: Circulation (2013)

Background and Objectives: In treating ST-elevation myocardial infarction (STEMI), early reperfusion therapy is very important. To reduce the ischemic time, pain-to-door time (PTD) might be importa...
From mice to men: A novel serum signature for prostate cancer diagnosis
Authors: S. Gillessen, I. Cima, A. Templeton, R. Schiess, S. Wyler, T. Leippold, H. Moch, T. Cerny, R. Aebersold, W. Krek
Journal: Journal of Clinical Oncology (2008)

11015 Background: Sensitivity and specificity of prostate specific antigen (PSA) for prostate cancer (CaP) detection are limited. Hence, discovery and validation of new biomarkers is important. We hypothesized that a comprehensive knowledge of the glycoproteome of CaP will allow a targeted search for serum glycopeptides and thus be a novel approach to uncover new biomarkers. Methods: We have established a new platform for human biomarker discovery that is based on the initial identification of the glycoproteome of the PTEN conditional knockout (cKO) mouse CaP model and the subsequent search of shed glycopeptides in the sera of mice and men. N- glycopeptides from murine prostate tissue and serum are enriched using a hydrazide chemistry-based approach. Label-free quantitation is performed to compare the differentially expressed glycoproteins in tumorigenic vs. normal prostate. Interesting proteins are monitored in the corresponding murine sera by targeted mass spectrometry. Potential biomarkers are then validated in human sera using standard ELISA techniques and targeted mass spectrometry. Fisher discriminance analysis is used as a multivariate statistical model to detect a signature for best discrimination between benign prostatic hyperplasia (BPH) and CaP. Results: We identified 153 proteins with interesting properties, among which 6 have now been validated in human sera. All 6 showed a significant differential expression in sera from patients with CaP compared to BPH. A multivariate model was created to distinguish between sera collected from 37 patients with BPH (n=19) or CaP (n=18). Using leave one-out cross-validation, the 6-biomarker signature had an accuracy of 78% (sens. 56%; spec. 100%), in comparison to PSA with an accuracy of 62% (sens. 28%; spec. 95%). By combining PSA with the 6-biomarker signature accuracy was further improved to 84% (sens. 72%; spec. 95%). Conclusions: By establishing a PTEN-dependent CaP glycoproteome catalogue, we were able to develop a new targeted approach to serum biomarker discovery. Specifically, we identified a novel 6-biomarker signature that can in addition to PSA potentially be used for improved diagnosis of human CaP. We propose that the glycoproteome of a tumor may be a good starting point for an unbiased sensitive search for cancer signatures in human serum. No significant financial relationships to disclose.
Noninvasive fatty liver markers predict liver disease mortality in the U.S. population
Authors: Aynur Unalp‐Arida, Constance E. Ruhl
Journal: Hepatology (2015)

Nonalcoholic fatty liver disease (NAFLD) contributes to premature death along with obesity, diabetes, and cardiovascular disease (CVD). We examined whether hepatic steatosis (HS) on ultrasound and liver enzyme activities were associated with increased liver disease mortality in the U.S. National Health and Nutrition Examination Survey (NHANES), 1988‐1994, with up to 23 years of linked‐mortality data. Survey‐linked National Death Index records were analyzed among 14,527 adult participants who were negative for viral hepatitis B and C and iron overload. HS on ultrasound was categorized as normal, mild, moderate, or severe. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma‐glutamyltransferase (GGT) elevation was defined as the highest sex‐specific decile. Cumulative mortality was 36.2% from all causes, including 16.3% from CVD, 10.8% from cancer, 5.4% from diabetes, and 1.1% from liver disease. Severe HS was associated with increased liver disease mortality in both age‐adjusted (hazard ratio [HR]: 3.92; 95% confidence interval [CI]: 1.49‐10.27; P for trend: 0.011) and multivariate‐adjusted analyses (HR, 2.68; 95% CI: 1.02‐7.03; P for trend: 0.072). HS was not independently associated with mortality from all causes, CVD, cancer, or diabetes. Higher liver disease mortality was found with elevated ALT (HR, 4.08; 95% CI: 1.99‐8.33), AST (HR, 4.33; 95% CI: 2.18‐8.59), and GGT (HR, 7.91; 95% CI: 3.06‐20.46). GGT elevation was associated with increased overall mortality (HR, 1.45; 95% CI: 1.21‐1.74). Liver enzymes were otherwise unrelated to overall or cause‐specific mortality. Conclusions: In the U.S. population, severe hepatic steatosis on ultrasound and liver enzyme elevation were associated with increased liver disease mortality, but were not independently associated with mortality from all causes (except for GGT), CVD, cancer, or diabetes. (H epatology 2016;63:1170–1183)
Long-Term Results of a Multicenter Randomized Phase III Trial of Induction Chemotherapy With Cisplatin, 5-fluorouracil, ± Docetaxel for Larynx Preservation
Authors: Guillaume Janoray, Yoann Pointreau, Pascal Garaud, Sophie Chapet, Marc Alfonsi, Christian Sire, Eric Jadaud, Gilles Calais
Journal: JNCI Journal of the National Cancer Institute (2015)

Background:The purpose of GORTEC 2000–01 was to compare the long-term efficacy and safety of induction chemotherapy with cisplatin (P) and 5-fluorouracil (F) with or without docetaxel (T) for larynx preservation.
Carbon monoxide encephalopathy: need for appropriate treatment
Authors: R Ginsburg, J Romano
Journal: American Journal of Psychiatry (1976)

The authors describe severe psychiatric and neurological sequelae in a patient who suffered carbon monoxide poisoning as a result of a suicide attempt. A review of the literature revealed that 15 to 40% of survivors of carbon monoxide poisoning develop neuropsychiatric symptoms, often following a period of apparent recovery. The authors advocate an aggressive treatment approach to carbon monoxide poisoning, emphasize the diagnostic value of extensive laboratory testing, and suggest that 2 to 4 weeks of bedrest may prevent delayed neuropsychiatric sequelae.
Weekly high-dose methotrexate and doxorubicin for osteosarcoma: the Dana-Farber Cancer Institute/the Children's Hospital--study III.
Authors: A M Goorin, A Perez-Atayde, M Gebhardt, J W Andersen, R H Wilkinson, M J Delorey, H Watts, M Link, N Jaffe, E Frei
Journal: Journal of Clinical Oncology (1987)

Weekly high-dose methotrexate with leucovorin rescue and vincristine (HDMTX) and doxorubicin was administered as adjuvant postoperative therapy to 46 patients with a diagnosis of conventional high-grade nonmetastatic osteosarcoma of an extremity between July 1976 and December 1981. The primary lesions were managed by wide or radical amputation (26 patients) or by limb-sparing resection in 20 selected patients. The margins of the resections were retrospectively classified as marginal in three, wide in 16, and radical in one. The 5-year relapse-free survival (RFS) for all patients is 59% (95% confidence interval [CI], 43%, 74%) and overall survival is 78% (95% CI, 65%, 91%). The RFS for patients initially having a limb resection procedure is 55% (95% CI, 32%, 77%) compared with 62% (95% CI, 43%, 81%) for those initially having amputations (P = .52). Using multivariate analysis, the only significant prognostic variables that predicted RFS of greater than or equal to 3 years, were the presence of moderate to marked lymphocytic infiltration of the primary tumor (P less than .002), primary site outside of the proximal humerus (P less than .005), and the absence of a predominance of osteoblastic pattern in the primary tumor (P less than .03).
CIDANE: comprehensive isoform discovery and abundance estimation
Authors: Stefan Canzar, Sandro Andreotti, David Weese, Knut Reinert, Gunnar W. Klau
Journal: Genome biology (2016)

We present CIDANE, a novel framework for genome-based transcript reconstruction and quantification from RNA-seq reads. CIDANE assembles transcripts efficiently with significantly higher sensitivity and precision than existing tools. Its algorithmic core not only reconstructs transcripts ab initio, but also allows the use of the growing annotation of known splice sites, transcription start and end sites, or full-length transcripts, which are available for most model organisms. CIDANE supports the integrated analysis of RNA-seq and additional gene-boundary data and recovers splice junctions that are invisible to other methods. CIDANE is available at http://ccb.jhu.edu/software/cidane/.
Estrogen, Progesterone, and Androgen Receptors in Breast Cancer in the Japanese: Brief Communication 2
Authors: H. Ochi, T. Hayashi, K. Nakao, T. Kawahara, K. Matsumoto
Journal: JNCI Journal of the National Cancer Institute (1978)

Estrogen, progesterone, and androgen receptors (ER, PgR, and AR, respectively) were determined by dextran-coated charcoal assay analyzed with Scatchard plots in cytosols from 81 Japanese patients with breast cancer. For the estimations of PgR and AR, the following compounds were used: a synthetic progestin, [3H]R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione), not bound by corticosteroid-binding globulin; and a synthetic androgen, [3H]R1881 (17beta-hydroxy-17-methylestra-4,9,11-trien-3-one), not bound by human sex steroid plasma-binding protein. Forty-two of 81 of the cancers revealed measurable amounts of ER (greater than 2 fmoles/mg cytosol protein), whereas the rates of measurable amounts of PgR (greater than 5) and AR (greater than 5) were 27% (18/67) and 36% (17/47), respectively. PgR were found in 45% of cancer patients with ER, but in only 9% of the cancer patients without ER. AR were found in 50% of the cancer patients with ER, but in only 22% of the cancer patients without ER. These results are consistent with those reported by Western investigators.
Interleukin-1 administration before lethal irradiation and allogeneic bone marrow transplantation: early transient increase of peripheral granulocytes and successful engraftment with accelerated leukocyte, erythrocyte, and platelet recovery
Authors: P Tiberghien, V Laithier, M Mabed, E Racadot, CW Reynolds, R Angonin, R Loumi, JJ Pavy, JY Cahn, A Noir
Journal: Blood (1993)
Effects of marihuana on adolescents and young adults
Authors: H. Kolansky
Journal: JAMA (1971)

The large amount of marihuana smoking (12 million to 20 million people) in this country was reviewed, as well as some of the literature concerning adverse effects. Thirty-eight individuals from age 13 to 24 years, all of whom smoked marihuana two or more times weekly, were seen by us between 1965 and 1970, and all showed adverse psychological effects. Some also showed neurologic signs and symptoms. Of the 20 male and 18 female individuals seen, there were eight with psychoses; four of these attempted suicide. Included in these cases are 13 unmarried female patients who became sexually promiscuous while using marihuana; seven of these became pregnant.
IL-1–induced Bhlhe40 identifies pathogenic T helper cells in a model of autoimmune neuroinflammation
Authors: Chih-Chung Lin, Tara R. Bradstreet, Elizabeth A. Schwarzkopf, Nicholas N. Jarjour, Chun Chou, Angela S. Archambault, Julia Sim, Bernd H. Zinselmeyer, Javier A. Carrero, Gregory F. Wu, Reshma Taneja, Maxim N. Artyomov, John H. Russell, Brian T. Edelson
Journal: The Journal of Experimental Medicine (2016)

The features that define autoreactive T helper (Th) cell pathogenicity remain obscure. We have previously shown that Th cells require the transcription factor Bhlhe40 to mediate experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Here, using Bhlhe40 reporter mice and analyzing both polyclonal and TCR transgenic Th cells, we found that Bhlhe40 expression was heterogeneous after EAE induction, with Bhlhe40-expressing cells displaying marked production of IFN-γ, IL-17A, and granulocyte-macrophage colony-stimulating factor. In adoptive transfer EAE models, Bhlhe40-deficient Th1 and Th17 cells were both nonencephalitogenic. Pertussis toxin (PTX), a classical co-adjuvant for actively induced EAE, promoted IL-1β production by myeloid cells in the draining lymph node and served as a strong stimulus for Bhlhe40 expression in Th cells. Furthermore, PTX co-adjuvanticity was Bhlhe40 dependent. IL-1β induced Bhlhe40 expression in polarized Th17 cells, and Bhlhe40-expressing cells exhibited an encephalitogenic transcriptional signature. In vivo, IL-1R signaling was required for full Bhlhe40 expression by Th cells after immunization. Overall, we demonstrate that Bhlhe40 expression identifies encephalitogenic Th cells and defines a PTX–IL-1–Bhlhe40 pathway active in EAE.
O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation and relation to 1p/19q loss in low grade gliomas: A GICNO study
Authors: L. Nicolardi, R. Bertorelle, L. Bonaldi, A. Compostella, A. Roma, E. Tebaldi, A. Pession, M. Reni, E. Franceschi, C. Ghimenton
Journal: Journal of Clinical Oncology (2006)

20064 Background: 1p and 19q deletions have been associated with a favorable response to chemotherapy and a good prognosis in patients (pts) with oligodendroglioma. MGMT promoter methylation has been associated with a longer survival in pts with glioblastoma who receive alkylating agents. As yet, there are no data on the expression of MGMT, and on the relationship between 1p/19q deletions and MGMT promoter methylation in low grade glioma (LGG). Methods: Pts that received a first line chemotherapy regimen with temozolomide for progressive LGG were enrolled in the study, designed to investigate the correlation between MGMT methylation status and 1p/19q deletions in this setting. 1p/19q deletions were analysed by FISH, and MGMT promoter methylation by methylation specific PCR (MSP). Results: Seventy-five pts (26 females, 49 males; median age 42 years: range 22–68 years) were accrued. Of these, 48 (64%) had oligodendrogliomas (O), 19 (25.3%) astrocytomas (A), and 8 (10.6%) oligoastrocytomas (OA); 44 (58.7%) had a history of epilepsy, 41 (54.7%) had a frontal tumor localization, 27 (36%) had MRI contrast enhancing lesions, and 35 (46.7%) had been pre-treated with radiotherapy. 1p/19q deletions, evaluable in 58 pts (77.3%), were both present in 36 pts (62%), (3 being A and 2 OA); 18 pts (31%) had no loss; 1 pt (1.7%) had 1p loss; 3 pts (5.2%) 19q loss. Combined 1p and 19q loss was not correlated with a frontal localization (p = 0.12), median age (0.47) and/or gender (0.62). MGMT promoter methylation, present in 17 (56.6%) of 30 assessable cases, was significantly associated with combined 1p/19q deletions (p = 0.03). MGMT promoter methylation was not significantly associated with age (p = 0.46), gender (p = 0.2), tumor localization (p = 0.12) and/or histology (0.37). Conclusions: 1p/19q deletions are strictly correlated to histology and to MGMT promoter methylation; further prospective trials are required to clarify the impact of these molecular signatures on clinical outcome. No significant financial relationships to disclose.
Quantitative Aspects of Carcinoembryonic Antigen Output by a Human Lung Carcinoma Cell Line
Authors: Morag L. Ellison, Lamb Denise, J. Rivett, A. Munro Neville
Journal: JNCI Journal of the National Cancer Institute (1977)

The release of carcinoembryonic antigen (CEA) or CEA-like material by a bronchial carcinoma cell line has been studied in more than 80 in vitro passages. The CEA output remained constant in culture over this period, provided the environmental conditions remained constant. Under such conditions, the amount of CEA released was proportional to the number of tumor cells in the culture. However, when the culture conditions were changed, the cell growth rate also changed, with consequent alteration in CEA release such that the amounts were inversely proportional to the rate of growth of the cells. If the cells were exposed to toxic conditions, CEA was released immediately. The implications of the quantitative relationship of CEA to the tumor cells which produce it were examined with reference to the potential of CEA as a clinical tumor index material.
A phase I trial of the small molecule pan-bcl-2 inhibitor obatoclax (GX15–070) in combination with docetaxel in patients with relapsed non-small cell lung cancer (NSCLC)
Authors: E. B. Haura, C. A. Williams, A. A. Chiappori, J. Adams, D. W. Northfelt, S. M. Malik, D. Van Echo, M. J. Edelman, M. Berger
Journal: Journal of Clinical Oncology (2008)

19035 Background: Over expression of bcl-2 family proteins is common in NSCLC and the BH-3 mimetic obatoclax (O) induces apoptosis in a subset of NSCLC where it synergizes with cisplatin (Li et al., Cancer Chemother. Pharmacol., 2008). Single agent O has shown clinical activity in hematological indications across 3 Phase I trials. This is the first trial combining O with a cytotoxic, docetaxel (D). Methods: Eligibility criteria included advanced stage IIIB/IV NSCLC, prior paclitaxel (but not D) allowed, measurable disease, ECOG PS ≤1, disease progression, adequate hematological, renal and hepatic function. D given as a 1 h infusion on day1 followed by flat dose O given as a 24 h continuous infusion on days 1 and 2, every 3 weeks for up to 8 cycles. Dose Level 1: D 55 mg/m2 and O 30 mg X 2; Dose Level 2: D 75 mg/m2 and O 30 mg X 2; Dose Level 3: D 75 mg/m2 and O 45 mg X 2; Dose Level 4: D 75 mg/m2 and O 60 mg X 2. PK samples were obtained at 1, 3, 24, 47 and 49 h after the start of the O infusion. Results: 18 patients enrolled (3, 3, 6 and 6 in consecutive Dose Levels). Patient characteristics: 11 male, median age = 62 (range= 44–81), PS = 0 in 11 and PS = 1 in 7, median prior regimens = 1 (range = 1–6). A total of 74 cycles were administered (median 4, range = 1–8). The only Grade 3–4 adverse events (AEs) were dyspnea (11%) and neutropenia (none in DL1, 60% in DL2–4). Known AEs of O were infrequent: somnolence only in 1/6 at DL4 and euphoria in 1/3 in DL2 and 1/6 in DL3. The mean ± SD plasma concentration of O at 1, 3, 24, 47, and 49 hr time-points from the start of infusion were 2.61±1.96, 2.00±1.43, 3.94±2.88, 4.04±3.33, and 1.61±0.86, respectively at 30 mg dose level. At 45 mg dose, the mean±SD concentrations at same time-points were 5.00±1.59, 6.21±2.24, 4.26±2.01, 7.32±2.84, and 2.42±1.30, respectively, and at 60 mg those concentrations were 5.03±4.61, 8.16±3.17, 10.34±7.34, 12.44±9.42, and 5.45±2.25, respectively. There have been 2 PRs (11%) and 4 confirmed SD (22%). Early PD was noted in 9 (50%). Conclusions: the BH3-mimetic O can be safely administered with D with no increase in neutropenia. The regimen described by DL4 is currently being evaluated in a phase II trial in relapsed NSCLC. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration GeminX GeminX
Hyperplastic and Neoplastic Alterations in the Livers of White Perch (&lt;italic&gt;Morone americana&lt;/italic&gt;) From the Chesapeake Bay
Authors: E B May, R Lukacovic, H King, M M Lipsky
Journal: JNCI Journal of the National Cancer Institute (1987)

White perch (Morone americana) sampled from 15 estuaries of the Chesapeake Bay contained a variety of hyperplastic and neoplastic alterations in their livers. The lesions were derived from bile ductular epithelium and/or hepatocytes. The biliary lesions consisted of hyperplasias and adenomas. The hepatocellular lesions consisted of focal populations of altered cells and neoplasms, of clear-cell and basophilic morphologic appearance. The hepatocellular lesions were conspicuous in the absence of the decreased amount of copper accumulation. In this respect, the cells comprising these lesions are reminiscent of cells from hepatocellular neoplasia in mice and rats resistant to accumulation of iron.
The Multifunctional, Multi-Institutional, and Sometimes Even Global Phase I Study: A Better Life for Phase I Evaluations or Just “Living Large”?
Authors: Anthony W. Tolcher, Chris H. Takimoto, Eric K. Rowinsky
Journal: Journal of Clinical Oncology (2002)

Article Tools EDITORIALS Article Tools OPTIONS & TOOLS Export Citation Track Citation Add To Favorites Rights & Permissions COMPANION ARTICLES No companion articles ARTICLE CITATION DOI: 10.1200/JCO.2002.20.21.4276 Journal of Clinical Oncology - published online before print September 21, 2016 PMID: 12409324 The Multifunctional, Multi-Institutional, and Sometimes Even Global Phase I Study: A Better Life for Phase I Evaluations or Just “Living Large”? Anthony W. TolcherxAnthony W. TolcherSearch for articles by this author , Chris H. TakimotoxChris H. TakimotoSearch for articles by this author , Eric K. RowinskyxEric K. RowinskySearch for articles by this author Show More Institute for Drug Development, Cancer Therapy and Research Center, University of Texas Health Science Center at San Antonio, San Antonio, TX https://doi.org/10.1200/JCO.2002.20.21.4276 First Page Full Text PDF Figures and Tables © 2002 by American Society of Clinical Oncology