tbuckley/cabot-search huggingface dataset:
Mitochondrial Resequencing Arrays Detect Tumor-Specific Mutations in Salivary Rinses of Patients with Head and Neck Cancer
Authors: Suhail K. Mithani, Ian M. Smith, Shaoyu Zhou, Andrew Gray, Wayne M. Koch, Anirban Maitra, Joseph A. Califano
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Alterations of the mitochondrial genome have been identified in multiple solid tumors and in many head and neck squamous cell carcinomas (HNSCC). Identification of mitochondrial mutations in the salivary rinses of patients with HNSCC has potential application in disease detection. In this study, we used the MitoChip v2.0 mitochondrial genome resequencing array to detect minor populations of mitochondrial DNA in salivary rinses of patients with HNSCC. Experimental Design: Salivary rinses from 13 patients with HNSCC, whose tumors carried mitochondrial mutations, were collected before surgical resection. DNA isolated from salivary rinses and serial dilutions of DNA derived from HNSCC-derived cell lines with known mitochondrial mutations were sequenced using the MitoChip, and analyzed using a quantitative algorithm which we developed to detect minor populations of mitochondrial DNA from MitoChip probe intensity data. Results: We detected heteroplasmic populations of mitochondrial DNA up to a 1:200 dilution using MitoChip v2.0 and our analysis algorithm. A logarithmic relationship between the magnitude of assay intensity and concentration of minor mitochondrial populations was shown. This technique was able to identify tumor-specific mitochondrial mutations in salivary rinses from 10 of 13 (76.9%) patients with head and neck cancer. Conclusions: Minor populations of mitochondrial DNA and disease-specific mitochondrial mutations in salivary rinses of patients with HNSCC can be successfully identified using the MitoChip resequencing array and the algorithm which we have developed. This technique has potential application in the surveillance of patients after resection and may have applicability in the surveillance of body fluids in other tumor types.
Sarcoma Rejection in Mice Born of Mothers Actively Immunized Against Murine Leukemia Viruses&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: J. A. Otten, R. L. Tyndall, A. C. Upton
Journal: JNCI Journal of the National Cancer Institute (1970)

Transplantable sarcomas infected with Rauscher leukemia virus (RLV) were rejected by mice whose mothers were actively immunized with formalized preparations of RLV. Uninfected sarcomas were not rejected. The RLV-infected sarcomas were also rejected by mice whose mothers were actively immunized with Friend leukemia virus preparations, but not with extracts from AKR mouse lymphomas. Foster-nursing experiments indicated that protection could be transferred from mother to newborn through the milk. The protective effect of sera from immunized mice could also be demonstrated in an in vitro microcytotoxic test with an established cell culture infected with RLV as the target cell.
Parental Alcohol Consumption, Cigarette Smoking, and Risk of Infant Leukemia: a Childrens Cancer Group Study
Authors: X.-O. Shu, J. A. Ross, T. W. Pendergrass, G. H. Reaman, B. Lampkin, L. L. Robison
Journal: JNCI Journal of the National Cancer Institute (1996)

Whether parental drinking and smoking during pregnancy are associated with an increased risk of cancer in offspring is controversial. There are some indications that maternal alcohol consumption is associated with an elevated risk of acute myeloid leukemia (AML) appearing in very young children. Evidence for an association between maternal smoking during pregnancy and risk of leukemia in offspring has been inconsistent.Using data from a Children's Cancer Group case-control study, we evaluated relationships between infant leukemia risk and parental alcohol consumption and/or cigarette smoking during pregnancy or during the month prior to it.Three hundred two leukemia cases (203 acute lymphoid leukemias [ALLs], 88 AMLs, and 11 other leukemia types) diagnosed in children at 18 months of age or younger and 558 individually matched, regional (i.e., same telephone area code and exchange number) controls were included in the analysis. Information concerning parental alcohol consumption and smoking behavior during the index pregnancy and during the month prior to it was collected by telephone interviews with the mothers of all case and control subjects and the fathers of 250 case and 361 control subjects. Odds ratios (ORs) were used to measure the risk of infant leukemia associated with parental smoking and drinking; tests for trend were used to assess dose-response relationships. The data were analyzed further after stratifying the leukemia cases according to histologic and morphologic types. Reported P values are from two-sided tests of statistical significance.Maternal drinking during pregnancy (compared with not drinking) was associated with ORs of 1.43 (95%) confidence interval [CI] = 1.00-2.04) for ALL and 2.64 (95% CI = 1.36-5.06) for AML. A dose-response relationship was observed for total maternal alcohol consumption during pregnancy and risk of AML (P < .01). Alcohol-related risk appeared to be most pronounced for children who developed AML with a morphology of M1 (myeloblastic with minimal maturation) or M2 (myeloblastic with maturation (OR = 7.62; 95% CI = 2.03-28.64). Paternal alcohol consumption did not confer an increased risk of infant leukemia. Maternal smoking during pregnancy (compared with not smoking) was negatively associated with infant leukemia risk (OR = 0.66 and 95% CI = 0.46-0.94 for total leukemia; OR = 0.45 and 95% CI = 0.21-0.96 for AML), whereas paternal smoking 1 month prior to pregnancy (compared with not smoking during the same period) was related to an elevated risk of ALL (OR = 1.56; 95% CI = 1.03-2.36).Maternal alcohol consumption during pregnancy increases the risk of infant leukemia, especially AML. Maternal smoking, however, does not elevate risk for either AML or ALL.The data suggest that in utero exposure to alcohol may contribute to leukemogenesis involving myeloid cells.
Noonan Syndrome Mutation Q79R in Shp2 Increases Proliferation of Valve Primordia Mesenchymal Cells via Extracellular Signal–Regulated Kinase 1/2 Signaling
Authors: Maike Krenz, Katherine E. Yutzey, Jeffrey Robbins
Journal: Circulation Research (2005)

The molecular pathways regulating valve development are only partially understood. Recent studies indicate that dysregulation of mitogen-activated protein kinase (MAPK) signaling might play a major role in the pathogenesis of congenital valvular malformations, and, in this study, we explored the role of extracellular signal-regulated kinase (ERK) 1/2 activation in valve primordia expressing the Noonan syndrome mutation Q79R-Shp2. Noonan syndrome is an autosomal dominant disease characterized by dysmorphic features and cardiac abnormalities, with frequent pulmonic stenosis. The Q79R mutation of PTPN11 previously identified in Noonan syndrome families results in a gain-of-function of the encoded protein tyrosine phosphatase Shp2. We compared the effects of wild-type Shp2 and Q79R-Shp2 on endocardial cushion development. Atrioventricular and outflow tract endocardial cushions were excised from chick embryos, infected with wild-type Shp2 or Q79R-Shp2 adenovirus and embedded in a gel matrix. Q79R-Shp2, but not wild-type-Shp2, expression resulted in increased outgrowth of cells into the gel. The dependence of the Q79R-Shp2 effect on ERK1/2 and p38 MAPK signaling was then determined. The MAPK/ERK kinase (MEK)-1 inhibitor U0126, but not the p38-MAPK pathway inhibitor SB203580, abolished the effect of Q79R-Shp2 on cushion outgrowth. Coinfection with Q79R-Shp2 and dominant negative MEK-1 prevented enhanced endocardial cushion outgrowth, whereas expression of constitutively active MEK-1 mimicked the effect of Q79R-Shp2. Furthermore, dissociated cushion cells displayed increased 5-bromodeoxyuridine incorporation when infected with Q79R-Shp2 but not with wild-type Shp2. This promitotic effect was eliminated by U0126. Our results demonstrate that ERK1/2 activation is both necessary and sufficient to mediate the hyperproliferative effect of a gain-of-function mutation of Shp2 on mesenchymal cells in valve primordia.
Augmented topological maps for three-dimensional navigation
Authors: Herbert Peremans, Dieter Vanderelst
Journal: Behavioral and Brain Sciences (2013)

Abstract We describe an augmented topological map as an alternative for the proposed bicoded map. Inverting causality, the special nature of the vertical dimension is then no longer fixed a priori and the cause of specific navigation behavior, but a consequence of the combination of the specific geometry of the experimental environment and the motor capabilities of the experimental animals.
Synergistic Effect of Bone Marrow Mobilization and Vascular Endothelial Growth Factor-2 Gene Therapy in Myocardial Ischemia
Authors: Atsuhiko Kawamoto, Toshinori Murayama, Kengo Kusano, Masaaki Ii, Tengiz Tkebuchava, Satoshi Shintani, Atsushi Iwakura, Ingrid Johnson, Patrick von Samson, Allison Hanley, Mary Gavin, Cindy Curry, Marcy Silver, Hong Ma, Marianne Kearney, Douglas W. Losordo
Journal: Circulation (2004)

We performed a series of investigations to test the hypothesis that combining angiogenic gene therapy and cytokine (CK)-induced endothelial progenitor cell mobilization would be superior to either strategy alone for treatment of chronic myocardial ischemia.A swine model of chronic myocardial ischemia and a murine model of acute myocardial infarction were used in this study. In both models, animals were randomly assigned to 1 of 4 treatment groups: Combo group, intramyocardial vascular endothelial growth factor (VEGF)-2 gene transfer plus subcutaneous injection of CKs; VEGF-2, VEGF-2 gene transfer plus saline subcutaneously injected; CK, empty vector transfer plus CKs; and control, empty vector plus subcutaneous saline. Acute myocardial infarction was also induced in wild-type mice 4 weeks after bone marrow transplantation from enhanced green fluorescent protein transgenic mice to permit observation of bone marrow-derived cells in the myocardium after acute myocardial infarction. In chronic myocardial ischemia, combination therapy resulted in superior improvement in all indexes of perfusion and function compared with all other treatment groups. In the bone marrow transplant mice, double immunofluorescent staining revealed that the combination of CK-induced mobilization and local VEGF-2 gene transfer resulted in a significant increase in the number of bone marrow-derived cells incorporating into the neovasculature, indicating that recruitment and/or retention of bone marrow-derived progenitors was enhanced by mobilization and that local VEGF-2 gene transfer can provide signals for recruitment or incorporation of circulating progenitor cells.Mobilization of endothelial progenitor cells with cytokines potentiates VEGF-2 gene therapy for myocardial ischemia and enhances bone marrow cell incorporation into ischemic myocardium.
FAS/FAS Ligand Ratio: A Marker of Oxaliplatin-Based Intrinsic and Acquired Resistance in Advanced Colorectal Cancer
Authors: Cristina Nadal, Joan Maurel, Rosa Gallego, Antoni Castells, Raquel Longarón, Maribel Marmol, Sergi Sanz, Rafael Molina, Marta Martin-Richard, Pere Gascón
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Oxaliplatin-5-fluorouracil combinations have increased responses in first-line therapy up to 40% in advanced colorectal cancer. Unfortunately, those patients who will respond are unknown and initially sensitive patients become rapidly resistant to current therapies. FAS (CD95) and FAS ligand (FASL; CD95L) have been implicated in chemosensitivity through leading to apoptosis in response to DNA-damaging drugs. Whereas the proapoptotic role of FAS and FASL is well characterized, the function of their soluble forms as predictors of chemosensitivity remains unknown. Patients and Methods: Blood samples were obtained from 68 patients with advanced colorectal cancer who received oxaliplatin-5-fluorouracil combinations in first-line therapy. Computed tomographic scans were done every 3 months and responses were evaluated by Response Evaluation Criteria in Solid Tumors criteria. ELISA soluble FAS and soluble FASL analysis were done before treatment and every 3 months until disease progression. Ratios between soluble FAS and soluble FASL were established and its values and variations through time were related to treatment responses. Results: We found a significant increase in soluble FAS levels and a significant decrease in FASL at 3 months compared with baseline (13.2 versus 10.02 ng/mL; P = 0.0001; 0.07 versus 0.14 ng/mL; P = 0.007, respectively). A significant increase in the soluble FASL levels up to 9 months (fourth to fifth extractions; 0.26 ng/mL) of therapy compared with first to third extractions (0.11 ng/mL; P = 0.003) was also found. A random effect regression statistical model determined that &amp;gt;1.2-fold increase in soluble FAS/soluble FASL ratio was a marker of chemosensitivity (P = 0.001). Conclusions: These data strongly indicate that an increment of soluble FAS/soluble FASL ratio after treatment could be an excellent marker of chemosensitivity in colorectal cancer. On the other hand, a decreased ratio after treatment can be a predictor of chemoresistance despite an initial response.
Carboxyterminal propeptide of type I procollagen in ELF: elevation in asbestosis, but not in pleural plaque disease
Authors: L. Lammi, L. Ryhänen, E. Lakari, J Risteli, P Pääkkö, M. Ruotsalainen, S Lähde, V.l. Kinnula
Journal: European Respiratory Journal (1999)

Markers of collagen metabolism may possibly be used in the assessment of pulmonary involvement in asbestosis-related pulmonary diseases. In this study the levels of the carboxyterminal propeptide of type I procollagen (PICP) and the aminoterminal propeptide of type III procollagen (PIIINP) were evaluated in bronchoalveolar lavage fluid (BALF), epithelial lining fluid (ELF) and serum from patients with asbestos related pulmonary and pleural involvement. Forty-two consecutive patients with occupational exposure to asbestos fibres, who underwent bronchoscopy and bronchoalveolar lavage (BAL) at the time of the diagnosis were investigated. Five patients were diagnosed as having asbestosis, while 37 showed no parenchymal involvement. Of the latter group, 25 had pleural plaques, while 12 had no detectable changes in chest radiographs. The patients were followed-up for an average of 7 yrs. The PICP in BALF and ELF was detectable in all patients with asbestosis and in 8/37 subjects without parenchymal involvement. The levels of PICP in BALF and ELF were significantly higher in the asbestosis group compared to the patients without asbestosis (9.8+/-1.8 microg x L(-1) versus 0.6+/-1.3 microg x L(-1), p&lt;0.001 and 488.9+/-208.8 microg x L(-1) versus 22.6+/-50.6 microg x L(-1), p&lt;0.001, respectively). Only 1 patient with asbestosis and 3 patients without parenchymal involvement had detectable levels of PIIINP in BALF. The serum levels of PICP and PIIINP did not differ between the patients with asbestosis and those with exposure to asbestos fibres without asbestosis and were within the normal range. None of the 37 patients exposed to asbestos fibres without parenchymal involvement at the baseline developed asbestosis during the follow-up period of 7 yrs. In conclusion, the data show that the carboxyterminal propeptide of procollagen type I, but not the aminoterminal propeptide of type III procollagen is highly elevated in bronchoalveolar lavage fluid and epithelial lining fluid in patients with asbestosis, but not in those without parenchymal involvement. This suggests that the determination of carboxyterminal propeptide of procollagen type I in bronchoalveolar lavage fluid could be used as a marker of parenchymal involvement in patients exposed to asbestos fibres.
Histone Deacetylase Inhibitor AR-42 Differentially Affects Cell-cycle Transit in Meningeal and Meningioma Cells, Potently Inhibiting <i>NF2</i>-Deficient Meningioma Growth
Authors: Sarah S. Burns, Elena M. Akhmametyeva, Janet L. Oblinger, Matthew L. Bush, Jie Huang, Volker Senner, Ching-Shih Chen, Abraham Jacob, D. Bradley Welling, Long-Sheng Chang
Journal: Cancer Research (2012)

Meningiomas constitute about 34% of primary intracranial tumors and are associated with increased mortality in patients with neurofibromatosis type 2 (NF2). To evaluate potential medical therapies for these tumors, we have established a quantifiable orthotopic model for NF2-deficient meningiomas. We showed that telomerase-immortalized Ben-Men-1 benign meningioma cells harbored a single nucleotide deletion in NF2 exon 7 and did not express the NF2 protein, merlin. We also showed that AR-42, a pan-histone deacetylase inhibitor, inhibited proliferation of both Ben-Men-1 and normal meningeal cells by increasing expression of p16(INK4A), p21(CIP1/WAF1), and p27(KIP1). In addition, AR-42 increased proapoptotic Bim expression and decreased anti-apoptotic Bcl(XL) levels. However, AR-42 predominantly arrested Ben-Men-1 cells at G(2)-M whereas it induced cell-cycle arrest at G(1) in meningeal cells. Consistently, AR-42 substantially decreased the levels of cyclin D1, E, and A, and proliferating cell nuclear antigen in meningeal cells while significantly reducing the expression of cyclin B, important for progression through G(2), in Ben-Men-1 cells. In addition, AR-42 decreased Aurora A and B expression. To compare the in vivo efficacies of AR-42 and AR-12, a PDK1 inhibitor, we generated and used luciferase-expressing Ben-Men-1-LucB cells to establish intracranial xenografts that grew over time. While AR-12 treatment moderately slowed tumor growth, AR-42 caused regression of Ben-Men-1-LucB tumors. Importantly, AR-42-treated tumors showed minimal regrowth when xenograft-bearing mice were switched to normal diet. Together, these results suggest that AR-42 is a potential therapy for meningiomas. The differential effect of AR-42 on cell-cycle progression of normal meningeal and meningioma cells may have implications for why AR-42 is well-tolerated while it potently inhibits tumor growth.
Steps to a better Belfast: physical activity assessment and promotion in primary care
Authors: Neil Heron, Mark A Tully, Michelle C McKinley, Margaret E Cupples
Journal: British Journal of Sports Medicine (2013)

Background Low physical activity (PA) levels which increase the risk of chronic disease are reported by two-thirds of the general UK population. Promotion of PA by primary healthcare professionals is advocated but more evidence is needed regarding effective ways of integrating this within everyday practice. This study aims to explore the feasibility of a randomised trial of a pedometer-based intervention, using step-count goals, recruiting patients from primary care. Method Patients, aged 35–75, attending four practices in socioeconomically deprived areas, were invited to complete a General Practice PA Questionnaire during routine consultations. Health professionals invited ‘inactive’ individuals to a pedometer-based intervention and were randomly allocated to group 1 (prescribed a self-determined goal) or group 2 (prescribed a specific goal of 2500 steps/day above baseline). Both groups kept step-count diaries and received telephone follow-up at 1, 2, 6 and 11 weeks. Step counts were reassessed after 12 weeks. Results Of the 2154 patients attending, 192 questionnaires were completed (8.9%). Of these, 83 were classified as ‘inactive’; 41(10 men; 31 women) completed baseline assessments, with the mean age of participants being 51 years. Mean baseline step counts were similar in group 1 (5685, SD 2945) and group 2 (6513, SD 3350). The mean increase in steps/day was greater in groups 1 than 2 ((2602, SD 1957) vs (748, SD 1997) p=0.005). Conclusions A trial of a pedometer-based intervention using self-determined step counts appears feasible in primary care. Pedometers appear acceptable to women, particularly at a perimenopausal age, when it is important to engage in impact loading activities such as walking to maintain bone mineral density. An increase of 2500 steps/day is achievable for inactive patients, but the effectiveness of different approaches to realistic goal-setting warrants further study.
Protective Role of Toll-like Receptor 4 during the Initiation Stage of Cutaneous Chemical Carcinogenesis
Authors: Nabiha Yusuf, Tahseen H. Nasti, J. Alan Long, Mohammed Naseemuddin, Alan P. Lucas, Hui Xu, Craig A. Elmets
Journal: Cancer Research (2008)

Abstract Toll-like receptors (TLR) activate multiple steps in inflammatory reactions in innate immune responses. They also activate signals that are critically involved in the initiation of adaptive immune responses. Many tumorigenic chemicals have been associated with endotoxin hypersensitivity mediated through TLR4. To determine the role of TLR4 in cutaneous skin carcinogenesis, we treated TLR4-deficient C3H/HeJ mice and the TLR4-normal C3H/HeN mice with the carcinogenic polyaromatic hydrocarbon 7,12-dimethylbenz(a)anthracene (DMBA). TLR4-deficient C3H/HeJ mice developed more tumors relative to the TLR4-normal C3H/HeN mice. Both C3H/HeN and C3H/HeJ mice developed a T-cell–mediated immune response to topically applied DMBA. Interestingly, the cell-mediated immune response was mediated by IFN-γ in C3H/HeN mice and by interleukin (IL)-17 in C3H/HeJ mice. Moreover, C3H/HeN mice had elevated circulating levels of IFN-γ following topical application of DMBA, whereas IL-17 was elevated in C3H/HeJ mice. The results of this study indicate that TLR4 plays an important role in the prevention of DMBA skin tumorigenesis and that this is associated with differences in the T-cell subtype activated. Efforts to divert the cell-mediated immune response from one that is IL-17 mediated to one that is IFN-γ mediated may prove to be beneficial in the prevention of DMBA-induced cutaneous tumors. [Cancer Res 2008;68(2):615–22]
Hematopoietic stem cell transplantation for CD3δ deficiency
Authors: Nufar Marcus, Hidetoshi Takada, Jason Law, Morton J. Cowan, Juana Gil, Jose R. Regueiro, Diego Plaza Lopez de Sabando, Eduardo Lopez-Granados, Jignesh Dalal, Wilhelm Friedrich, Hoenig Manfred, Imelda Celine Hanson, Eyal Grunebaum, William T. Shearer, Chaim M. Roifman
Journal: Journal of Allergy and Clinical Immunology (2011)
Experimental rhesus lymphocryptovirus infection in immunosuppressed macaques: an animal model for Epstein-Barr virus pathogenesis in the immunosuppressed host
Authors: Pierre Rivailler, Angela Carville, Amitinder Kaur, Pasupuleti Rao, Carol Quink, Jeffery L. Kutok, Susan Westmoreland, Sherry Klumpp, Meredith Simon, Jon C. Aster, Fred Wang
Journal: Blood (2004)