tbuckley/cabot-search huggingface dataset:
P12.13 * SURGICAL TREATMENT OF BRAINSTEM TUMORS
Authors: A. Smolanka, T. Havryliv, V. Smolanka
Journal: Neuro-Oncology (2014)

OBJECTIVE: To determine the extent of resection and neurological outcomes after surgical treatment of brainstem tumors. METHODS: 34 patients with brainstem tumors operated in Regional Centre of Neurosurgery and Neurology from January, 2008 till January, 2014 were retrospectively analyzed. 20 (58.8%) patients were male, and 14 (41.2%) – female. Mean age of the patients was 22.7 years. Among them 16 (47.1%) were of pediatric age, 18 (52.9%) – adults. In 20 cases (58.8%) tumor had exophytic growth pattern into fourth ventricle. In purely intrinsic tumors (14 cases, 41.2%) the localization was: midbrain – 5 patients (14.7%), ponto-mesencephalic junction – 2 cases (5.9%), pons – 2 patients (5.9%), ponto-medullary junction – 2 cases (5.9 %), medulla oblongata – 3 patients (8.8%). Patients were examined neurologically on admission and one month after surgery. The extent of tumor resection was evaluated on early postoperative MRI (first 48 hours). RESULTS: Surgical approach was chosen individually in each case according to tumor location, using a 2-point method. In patients with midbrain tumors 3 different approaches were used: subtemporal (2 cases, 5.9%), occipital transtentorial (2 cases, 5.9%) and supracerebellar (1 patient, 2.9%). In 2 patients (5.9%) retrosigmoid approach was used. The “workhorse” approach in our series was median suboccipital with telo-velar entrance into the cavity of IV ventricle, which was used in 27 cases (79.4%). The tumors were resected through “safe entry” zones in the brainstem. In 28 cases (82.4%) gross total resection was achieved, in 6 patients (17.6%) the resection was subtotal (>90%). 5 patients (14.7%) deteriorated neurologically after surgery on 30 day follow-up, 29 patients (85.3%) improved or remained stable. None of the operated patients died. Histologic results: anaplastic ependymoma – 9 patients (26.5%), ependymoma – 5 patients (14.7%), pilocityc astrocytoma – 6 patients (17.6%), anaplastic astrocytoma – 4 patients (11.8%), medulloblastoma with significant brainstem invasion – 4 patients (11.8%), choroid plexus papilloma – 2 patients (5.9%), metastasis – 2 patients (5.9%), germinoma – 1 patient (2.9%), dermoid – 1 patient (2.9%). CONCLUSION: Surgical treatment of brainstem tumors can be done effectively (gross total removal in 82.4%) and relatively safe (morbidity – 14.7%, mortality – 0%).
The Effects of Antihypertensive Therapy on the Quality of Life
Authors: Sydney H. Croog, Sol Levine, Marcia A. Testa, Byron Brown, Christopher J. Bulpitt, C. David Jenkins, Gerald L. Klerman, Gordon H. Williams
Journal: New England Journal of Medicine (1986)

We conducted a multicenter randomized double-blind clinical trial among 626 men with mild to moderate hypertension to determine the effects of captopril, methyldopa, and propranolol on their quality of life. Hydrochlorothiazide was added if needed to control blood pressure. After a 24-week treatment period, all three groups had similar blood-pressure control, although fewer patients taking propranolol required hydrochlorothiazide. Patients taking captopril alone or in combination with a diuretic were least likely to withdraw from treatment because of adverse effects (8 percent vs. 20 percent for methyldopa and 13 percent for propranolol). The treatment groups were similar in scores for sleep dysfunction, visual memory, and social participation. However, patients taking captopril, as compared with patients taking methyldopa, scored significantly higher (P<0.05 to <0.01) on measures of general well-being, had fewer side effects, and had better scores for work performance, visual–motor functioning, and measures of life satisfaction. Patients taking propranolol also reported better work performance than patients taking methyldopa. Patients taking captopril reported fewer side effects and less sexual dysfunction than those taking propranolol and had greater improvement (P<0.05 to <0.01) on measures of general well-being. Our findings show that antihypertensive agents have different effects on the quality of life and that these can be meaningfully assessed with available psychosocial measures. (N Engl J Med 1986; 314:1657–64.)
Prognostic Value of a Four-Marker Panel Associated with Breast Cancer-Specific Survival
Authors: T.Z. Parris, A. Kovács, L. Aziz, S. Hajizadeh, S. Nemes, M. Semaan, E. Forssell-Aronsson, P. Karlsson, K. Helou
Journal: Annals of Oncology (2013)
Prolonged Injection Site Mass Can Occur with Methylene Blue but Not Lymphazurin Blue after the Sentinel Node Procedure.
Authors: I. Komenaka, G. Shirah, M. Bouton
Journal: Cancer Research (2009)

Abstract Objectives: The purpose of this study is to evaluate the differences in outcomes and complications of the sentinel node dissection for breast cancer using Methylene blue and Lymphazurin blue.Methods: From 2004-2008, 160 patients underwent the sentinel node procedure at a county hospital, teaching institution. The sentinel node procedure was performed using the combined technique of blue dye and radioactive isotope. From 2004 to June 2006, Lymphazurin blue (LB) was used. From July 2006 to 2008, Methylene blue (MB) was used. Axillary dissection was performed if the sentinel node procedure revealed positive lymph nodes or failed.Results: Fifty patients underwent the sentinel node procedure with LB and 110 underwent the procedure with MB. The patients were of similar age and stage of presentation. More patients in the MB group were Hispanic and underwent preoperative chemotherapy. The sentinel node identification rate was 100% in the LB group and 99% in the MB group (P = 1.0). The mean numbers of sentinel lymph nodes were similar (LB 2.2 vs. MB 2.7). In the LB group 34% of patients were lymph node positive compared to 40% in the MB group.There were no allergic reactions in either group. The infection rate in the breast was similar in both groups LB (2%) and MB (1.8%). Previous studies have reported skin manifestations of necrosis, ulceration, tattooing, erythema, rash, or telangiectasia/vascular change at the site of injection with methylene blue. These findings were not seen in any of the patients in this study. In ten of the 110 patients (9%) who underwent the procedure with MB, however, a local inflammatory reaction occurred which resulted in a palpable mass at the site of injection. No injection site reactions were noted in LB group. In the MB group, the masses were clearly more prominent than the surrounding breast tissue and identified either at the one week postoperative check (6) or at the first 6-month followup (4). Ultrasound of the injection sites did reveal a hypoechoic mass in one patient. Biopsies were performed on the first four patients, but revealed only inflammation and non-atypical hyperplasia. Nearly all of the masses resolved by one year, however, one resolved after 18 months.Conclusion: Methylene blue is a reasonable alternative to lymphazurin blue in the sentinel node procedure for breast cancer. Awareness of injection site reactions to MB are important, as a new dominant mass is always reason for concern in breast cancer patients. Palpable mass at the site of MB injection can occur but typically resolve over a one year period. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3115.
Abstract 3066: Comprehensive interactome of embryonic transcription factors, mitogenic stresses and miRNAs involved in breast tumorigenesis.
Authors: Emmanuelle Ruiz, Stephanie Courtois-Cox, Baptiste Gras, Amélie Veron, Stephane Ansieau, Alain Puisieux, Caroline MOYRET-LALLE
Journal: Cancer Research (2013)

Abstract Epithelial-to-Mesenchymal Transition (EMT) is associated with tumour initiation and progression. EMT is associated with a profound genetic reprogramming including reactivation of embryonic transcription factors (ETFs) and severe changes in miRNA expression. Cross-regulation between EMT-inducers and miRNAs was previously described like the Zeb1-miR-200 feed-back loop. Our goal is to determine whether specific expression networks between ETFs, miRNAs and mitogenic stresses exist in tumors, and represents a driving force towards transformation in breast tumorigenesis. We performed oncogenic cooperation assays in immortalized human mammary epithelial cells (HMEC-hTert) by using an EMT-inducer expression library in combination with various mitogenic stresses (activated form of beta-catenin, EGFR, shPTEN, shP53). As recently demonstrated in the laboratory, these combinations were efficient in transforming human cells, as assessed by soft-agar colony assay. EMT-inducer expression was next analyzed in a large number of colonies to evaluate a potential specificity of EMT-inducers according to the mitogenic insult. We found that expression of Slug was specifically enriched in colonies generated when EGFR is highly expressed, whereas Zeb1 expression was selected following PTEN depletion, p53 inactivation and beta-catenin activation. FoxC2 expression was enriched in cells expressing the activated form of beta-catenin. The prediction of specificity of the identified combinations is currently being validated by bioinformatics tools. In parallel, we developed an in silico approach utilizing predictive algorithms to identify novel miRNAs targeting embryonic transcription factors. We have identified two novel miRNAs able to regulate EMT inducers and we have validated their down-regulation in a panel of basal B breast cancer cell lines. We have also found new feedback loops between these two miRNA and some ETFs. The interplay between miRNAs, mitogenic proteins and EMT inducers will be further examined by assessing their expression in a large cohort of Basal B/ Claudin-low human breast tumours, a recently identified subtype displaying a mammary stem cell signature and EMT features. Citation Format: Emmanuelle Ruiz, Stephanie Courtois-Cox, Baptiste Gras, Amélie Veron, Stephane Ansieau, Alain Puisieux, Caroline MOYRET-LALLE. Comprehensive interactome of embryonic transcription factors, mitogenic stresses and miRNAs involved in breast tumorigenesis. [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 3066. doi:10.1158/1538-7445.AM2013-3066
ACTH and Cortisone in Diseases of the Skin
Authors: Walter F. Lever
Journal: New England Journal of Medicine (1951)

MORE than 70 patients with cutaneous diseases have been treated at Massachusetts General Hospital, Peter Bent Brigham Hospital, Robert Breck Brigham Hospital and Children's Hospital with ACTH or cortisone. Although it would be premature to draw definite conclusions, a preliminary, evaluation of the results obtained will be attempted.The fact that ACTH and cortisone are capable of suppressing allergic hypersensitivity reactions as well as inflammatory reactions not solely due to allergy explains the beneficial effect exerted by these drugs on many cutaneous diseases.In discussing the effects of ACTH and cortisone on cutaneous diseases one can divide these diseases into . . .
Abstract LB-160: CYP4F isoform expression and 20-HETE synthesis in prostate cancer cells are regulated by androgen and contribute to growth
Authors: Cheng-Chia Wu, Yunmeng Liu, Jonathan Chen, Katherine H. Gotlinger, Errabelli Ramu, John R. Falck, Michal L. Schwartzman
Journal: Cancer Research (2012)

Abstract 20-hydroxyeicosatetraenoic acid (20-HETE), a CYP450-derived arachidonic acid metabolite in the microcirculation, contributes to vascular tone and stimulates vascular and epithelial cell proliferation, angiogenesis and inflammation, all of which play a role in cancer progression. Our laboratory identified 20-HETE as the mediator of androgen-induced hypertension. Given that androgen contributes to the pathogenesis of prostate cancer, we examined the presence and function of 20-HETE in human prostate cancer cells. Androgen-responsive prostate cancer cells, LNCaP, produced 2-fold more 20-HETE compared to androgen-nonresponsive C4-2 cells (565±139 pg/mg protein vs 223±50 pg/mg protein). Both C4-2 and LNCaP produced greater amount of 20-HETE compared with U87 glioma, MCF-7 breast cancer and ML-1 thyroid cancer cells. 20-HETE levels in prostate primary stromal cells and epithelial RWPE-1 cells were barely detected (16±26 and 23±40 pg/mg protein respectively). Treatment of LNCaP with 5 alpha-dihydrotestosterone (DHT) stimulated 20-HETE production by 65% when compared to vehicle control. DHT treatment did not alter 20-HETE levels in C4-2. Treatment of C4-2 and LNCaP with HET0016, an inhibitor of 20-HETE synthesis, selectively decreased endogenous 20-HETE production while inhibiting cell growth in a dose-dependent manner. Further addition of exogenous 20-HETE stimulated growth. CYP4F2, CYP4F3 and CYP4F8 mRNA levels were several fold higher in LNCaP compared with C4-2, while levels of CYP4A11 and CYP4A22 mRNA were unchanged. In LNCaP, DHT increased CYP4F isoform expression without altering the CYP4A expression; flutamide abrogated DHT-induced expression of CYP4F2 and CYP4F3 but did not affect expression of CYP4F8. Importantly, flutamide inhibited DHT-stimulated 20-HETE production. These results suggest that 20-HETE has an important role in cancer cell proliferation and CYP4F2/3 might be the source of androgen-driven 20-HETE synthesis via androgen receptor dependent pathway. 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 LB-160. doi:1538-7445.AM2012-LB-160
A5.11 Bone formation inhibition and early bone loss correlated with arthritis outcome in rat adjuvant-induced arthritis
Authors: G Courbon, MT Linossier, N Laroche, L Vico, H Marotte
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background and objectives</h3> Rheumatoid arthritis (RA) features include synovial inflammation and periarticular bone loss. However, relationships between bone and synovia are not fully understood. We investigated early bone changes before inflammation onset in rat adjuvant-induced arthritis (AIA) and their predictability to later arthritis outcome. Bone loss is mainly due to resorption increase, already largely investigated. However, formation inhibition may be also involved and is poorly explored. Accordingly, we investigated gene expression regarding bone formation, resorption, and matrix degradation. <h3>Materials and methods</h3> Arthritis was induced (AIA, n = 35) or not (CTRL, n = 35) in female Lewis rats, and sacrificed at 7 stages. Ankle inflammation was recorded by articular index (AI), loss of function index (LFI), ankle perimeter, and in histological slides. Ankle bones microarchitecture was investigated with micro-computed tomography (µ-CT) and histomorphometry. Gene expression was assessed by quantitative RT-PCRs, and results were normalised to glyceraldehyde-3-phosphate deshydrogenase (GAPDH) expression. Non-parametric statistics were performed. P-values under 0.05 were considered statistically significant. <h3>Results</h3> As expected, inflammation parameters differed between CTRL and AIA rats from day 13 (AI, LFI, ankle perimeter, p &lt; 0.001, and weight, p &lt; 0.01), while ankle erosions where detected in µ-CT and histology in AIA rats from day 8. Early microarchitecture defects in ankles were quantifiable, and bone microarchitecture alterations at day 10 correlated with arthritis severity at day 17. Gene expression study revealed an upregulation of bone formation inhibitors such as dickkopf-related protein 1 (DKK1, p &lt; 0.05), secreted frizzled-related protein-1 (SFRP1, p &lt; 0.001), additionally to usual increase of bone resorption and degradation (RANK and RANKL upregulation, p &lt; 0.001 for both, osteoprotegerin downregulation, p &lt; 0.001), and bone matrix degradation (upregulation of matrix metalloproteinase (MMP)-2, p &lt; 0.05, MMP-9, p &lt; 0.001, and acid phosphatase, p &lt; 0.001). <h3>Conclusions</h3> Bone alterations might develop in parallel to synovial inflammation, giving new insights for bone compartment role in early RA joint and bone destruction. This early bone loss was predictive to arthritis outcome in the AIA model, and correlated with a lower but existing systemic bone loss. Finally, we observed that deregulation from both formation and resorption take part in this pattern.
1265 P53/P66SHC SIGNALING PATHWAY PLAYS A ROLE IN NONALCOHOLIC STEATOHEPATITIS PROGRESSION IN HUMAN AND MICE
Authors: K. Tomka, T. Teratani, T. Suzuki, H. Yokoyama, K. Shimamura, K. Nishiyama, Y. Okada, C. Kurihara, H. Ebinuma, H. Saito, R. Hokari, K. Sugiyama, K. Hatsuse, J. Yamamoto, T. Kanai, T. Hibi, S. Miura
Journal: Journal of Hepatology (2012)
ELEVATED PLASMA MARINOBUFAGENIN, AN ENDOGENOUS CARDIOTONIC STEROID, IS ASSOCIATED WITH RIGHT VENTRICULAR DYSFUNCTION AND NITRATIVE STRESS IN HEART FAILURE
Authors: Wai Hong Wilson Tang, Kevin Shrestha, Brendan Sheehy, Xinmin S. Li, Michael Finucan, Alaa Gabi, Anuradha Guggilam, Charles Medert, Kristen Westfall, Allen Borowski, Olga V. Fedorova, Olga V. Fedorova, Alexei Y. Bagrov, David Kennedy
Journal: Journal of the American College of Cardiology (2015)
New Delhi Congress Focuses on Cancer in the Developing World
Authors: S. Wagner, R. M. Romano
Journal: JNCI Journal of the National Cancer Institute (1994)

Journal Article New Delhi Congress Focuses on Cancer in the Developing World Get access Sally Wagner, Sally Wagner Search for other works by this author on: Oxford Academic PubMed Google Scholar Rose Mary Romano Rose Mary Romano Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 86, Issue 23, 7 December 1994, Pages 1750–1751, https://doi.org/10.1093/jnci/86.23.1750 Published: 07 December 1994
Public Trust in Physicians — U.S. Medicine in International Perspective
Authors: Robert J. Blendon, John M. Benson, Joachim O. Hero
Journal: New England Journal of Medicine (2014)

Among 29 industrialized countries, the United States ranks high in patients' satisfaction with their own care but low in public trust in the country's physicians. If the U.S. medical profession wants to influence health policy decisions, it must improve public trust.
Abstract 1790: The combination of MGCD265, a Met/VEGFR inhibitor in clinical development, and erlotinib potently inhibits tumor growth by altering multiple pathways including glycolysis
Authors: Claire Bonfils, Normand Beaulieu, Marielle Fournel, Helene Ste-Croix, Jeffrey M. Besterman, Christiane R. Maroun
Journal: Cancer Research (2012)

Abstract MGCD265 is an oral, multitargeted, receptor tyrosine kinase inhibitor in clinical development. MGCD265 targets the Met, VEGFR1, 2, 3, Tie2 and Ron receptor tyrosine kinases and blocks key pathways regulating cancer development and progression. Met-targeted agents, including MGCD265, have shown early signs of clinical activities when combined with EGFR inhibitors. While this combination is supported by a large body of evidence indicating that Met and EGFR functionally cooperate to amplify activating signals, how the combination of agents targeting these two pathways leads to efficient anti-tumor responses remains to be elucidated. We have previously demonstrated that the combination of MGCD265 with erlotinib achieved greater tumor growth inhibition than treatment with either agent alone in multiple xenografts including a gastric cancer model in which Met is amplified (MKN45). We performed gene expression analyses in this model to gain insight into the molecular mechanisms underlying the efficient anti-tumor activities of MGCD265 in combination with erlotinib. While these studies revealed the inhibition of cell growth and the induction of apoptosis pathways as enhanced by this combination, the regulation of glycolysis surfaced as a novel pathway altered by this combination. Although genes regulating this pathway were partly downmodulated by either agent alone, the combination significantly enhanced this effect. A key mediator of glycolysis, hexokinase 2 (HK2), known to be elevated in cancer cells and essential for the switch to aerobic glycolysis as well as for mitochondrial-initiated cell death, was significantly downregulated by the combination. Furthermore, PFKFB3, PGK, ENO1, PKM2 were also inhibited by the combination. These results suggest that regulating tumor cell glycolysis may present a novel pathway through which MGCD265 could block tumor cell growth. Thus, the inhibition of multiple molecular pathways involved in cancer growth and progression provides a rationale for the clinical development of MGCD265 in combination with erlotinib. Early results from an ongoing Phase I/II clinical trial of MGCD265 in combination with erlotinib has demonstrated encouraging signs of activity in gastric cancer patients. 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 1790. doi:1538-7445.AM2012-1790
Abstract 4403: Differential cytotoxic effects of atorvastatin in human hepatocellular carcinoma and pancreatic adenocarcinoma cells
Authors: Maria B. Lai, Vikas Bhardwaj, James CK Lai, Alok Bhushan
Journal: Cancer Research (2011)

Abstract Statins are lipid-lowering drugs that inhibit 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, the rate-limiting step in cholesterol synthesis. During cholesterol synthesis, isoprenoid intermediates are also formed which prenylate Ras and Rho proteins. Upon prenylation and transportation to the plasma membrane, Ras and Rho may interact with other molecules to partake in a signaling cascade that eventually lead to cell survival and proliferation. When statins inhibit cholesterol synthesis, they also inhibit the formation of these isoprenoid. Our studies focus on the potential anticancer effects of a statin (atorvastatin) in human hepatocellular carcinoma (HepG2) and pancreatic adenocarcinoma (AsPC-1) cells. We hypothesized that atorvastatin enhances cytotoxic effects of cisplatin in HepG2 and AsPC-1 treated cells. By utilizing a cell survival assay and western blot analysis, we found marked differences between the two cell lines after atorvastatin treatment. Our results indicate that treatment with atorvastatin at a concentration range of 0.1 µM to 20 µM for 48 and 72 hours significantly decreased cell survival of AsPC-1 cells, but not that of HepG2 cells. The IC50 value for atorvastatin in AsPC-1 treated cells was 3.5 µM; whereas, no effect on HepG2 cell survival was observed even at 20 µM concentration. Treatment with atorvastatin in combination with cisplatin in HepG2 cells did not potentiate the decrease in cell survival as compared to cisplatin treatment alone. However, treatment with 10 µM of atrovastatin in combination with 20 µM of cisplatin for 72 hours antagonized the effects of cisplatin treatment alone. After 48 hour treatments with atorvastatin, HepG2 and AsPC-1 cells had differential p-ERK expression, which could be an important factor in atorvastatin-induced cell death. Our preliminary findings suggest that statin treatment may be beneficial as a therapeutic avenue for pancreatic cancer but may not have the same benefits for liver cancer. The specific molecular mechanisms that decrease cancer cell survival following statin treatment have not been well understood and needs to be further studied. [Our project is supported by in part from NIH INBRE Grant P20RR016454]. 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 4403. doi:10.1158/1538-7445.AM2011-4403