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Author Vidaurre, T.; Santos, C.; Gomez, H.; Sarria, G.; Amorin, E.; Lopez, M.; Regalado, R.; Manrique, J.; Tarco, D.; Ayestas, C.; Calderon, M.; Mas, L.; Neciosup, S.; Salazar, M.; Chavez, J.C.; Ubillus, M.; Limache, A.; Ubillus, J.C.; Navarro, J.; Sarwal, K.; Sutcliffe, S.; Gutierrez-Aguado, A.; Silva, M.; Mena, A.; Guillen, M.E.; Castaneda, C.; Abugattas, J.
Title (down) The implementation of the Plan Esperanza and response to the imPACT Review Type Journal Article
Year 2017 Publication The Lancet. Oncology Abbreviated Journal Lancet Oncol
Volume 18 Issue 10 Pages e595-e606
Keywords Delivery of Health Care/organization & administration; Developing Countries; Early Detection of Cancer/*economics; Female; Health Care Costs; *Health Expenditures; Health Planning/*organization & administration; Humans; Male; Needs Assessment; Peru; Poverty; Preventive Medicine/*organization & administration; Risk Assessment
Abstract Following the implementation of the National Cancer Prevention and Control Results-based Budget Programme (PpR Cancer-024) in 2011, the Peruvian Government approved the Plan Esperanza-a population-based national cancer control plan-in 2012. Legislation that ensured full government-supported funding for people who were otherwise unable to access or afford care and treatment accompanied the Plan. In 2013, the Ministry of Health requested an integrated mission of the Programme of Action for Cancer Therapy (imPACT) report to strengthen cancer control in Peru. The imPACT Review, which was executed in 2014, assessed Peru's achievements in cancer control, and areas for improvement, including cancer control planning, further development of population-based cancer registration, increased prevention, early diagnosis, treatment and palliative care, and the engagement and participation of civil society in the health-care system. This Series paper gives a brief history of the development of the Plan Esperanza, describes the innovative funding model that supports it, and summarises how funds are disseminated on the basis of disease, geography, and demographics. An overview of the imPACT Review, and the government's response in the context of the Plan Esperanza, is provided. The development and execution of the Plan Esperanza and the execution of and response to the imPACT Review demonstrates the Peruvian Government's commitment to fighting cancer across the country, including in remote and urban areas.
Address National Institute of Neoplastic Diseases, Lima, Peru
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1470-2045 ISBN Medium
Area Expedition Conference
Notes PMID:28971826 Approved no
Call Number ref @ user @ Serial 97626
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Author Clark, P.A.; Gaal, J.T.; Strebe, J.K.; Pasch, C.A.; Deming, D.A.; Kuo, J.S.; Robins, H.I.
Title (down) The effects of tumor treating fields and temozolomide in MGMT expressing and non-expressing patient-derived glioblastoma cells Type Journal Article
Year 2017 Publication Journal of Clinical Neuroscience : Official Journal of the Neurosurgical Society of Australasia Abbreviated Journal J Clin Neurosci
Volume 36 Issue Pages 120-124
Keywords Antineoplastic Agents, Alkylating/*pharmacology; Cell Line, Tumor; Cell Proliferation/drug effects/radiation effects; Cell Survival/drug effects/radiation effects; Cells, Cultured; DNA Modification Methylases/genetics/*metabolism; DNA Repair Enzymes/genetics/*metabolism; Dacarbazine/*analogs & derivatives/pharmacology; *Electromagnetic Fields; Glioblastoma/genetics/*metabolism; Humans; Neoplastic Stem Cells/drug effects/radiation effects; Neurons/drug effects/radiation effects; Tumor Suppressor Proteins/genetics/*metabolism; Cancer stem cells; Glioblastoma; MGMT methylation; Temozolomide; Tumor treating fields
Abstract A recent Phase 3 study of newly diagnosed glioblastoma (GBM) demonstrated the addition of tumor treating fields (TTFields) to temozolomide (TMZ) after combined radiation/TMZ significantly increased survival and progression free survival. Preliminary data suggested benefit with both methylated and unmethylated O-6-methylguanine-DNA methyl-transferase (MGMT) promoter status. To date, however, there have been no studies to address the potential interactions of TTFields and TMZ. Thus, the effects of TTFields and TMZ were studied in vitro using patient-derived GBM stem-like cells (GSCs) including MGMT expressing (TMZ resistant: 12.1 and 22GSC) and non-MGMT expressing (TMZ sensitive: 33 and 114GSC) lines. Dose-response curves were constructed using cell proliferation and sphere-forming assays. Results demonstrated a 10-fold increase in TMZ resistance of MGMT-expressing (12.1GSCs: IC50=160muM; 22GSCs: IC50=44muM) compared to MGMT non-expressing (33GSCs: IC50=1.5muM; 114GSCs: IC50=5.2muM) lines. TTFields inhibited 12.1 GSC proliferation at all tested doses (50-500kHz) with an optimal frequency of 200kHz. At 200kHz, TTFields inhibited proliferation and tumor sphere formation of both MGMT GSC subtypes at comparable levels (12.1GSC: 74+/-2.9% and 38+/-3.2%, respectively; 22GSC: 61+/-11% and 38+/-2.6%, respectively; 33GSC: 56+/-9.5% and 60+/-7.1%, respectively; 114 GSC: 79+/-3.5% and 41+/-4.3%, respectively). In combination, TTFields (200kHz) and TMZ showed an additive anti-neoplastic effect with equal efficacy for TTFields in both cell types (i.e., +/- MGMT expression) with no effect on TMZ resistance. This is the first demonstration of the effects of TTFields on cancer stem cells. The expansion of such studies may have clinical implications.
Address University of Wisconsin Carbone Cancer Center, UWSMPH, United States; Division of Hematology and Oncology, Department of Medicine, UWSMPH, United States; William S Middleton Memorial Veterans Hospital, Madison, WI, United States; Department of Neurology, UWSMPH, United States; Department of Human Oncology, UWSMPH, United States. Electronic address: hirobins@wisc.edu
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0967-5868 ISBN Medium
Area Expedition Conference
Notes PMID:27865821 Approved no
Call Number ref @ user @ Serial 96622
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Author Goetz, L.G.; Valeggia, C.
Title (down) The ecology of anemia: Anemia prevalence and correlated factors in adult indigenous women in Argentina Type Journal Article
Year 2017 Publication American Journal of Human Biology : the Official Journal of the Human Biology Council Abbreviated Journal Am J Hum Biol
Volume 29 Issue 3 Pages
Keywords
Abstract OBJECTIVES: The Toba/Qom of Namqom are an indigenous community native to the Gran Chaco region of northern Argentina. Historically seminomadic foragers, the diet of peri-urban community members has rapidly changed from high-protein, high-fiber to hypercaloric, processed. This study aims to understand the impact of this nutritional transition on aspects of women's health by exploring the relationship between prevalence of anemia and current diet composition, place of birth, and reproductive history. METHODS: We measured the capillary hemoglobin (Hb) levels of 153 adult women. Each participant was also given two interviews characterizing reproductive history and a 24-hour food recall. RESULTS: The average Hb level was 12.6 g/dL (range 5.8-15.7 g/dL). In our sample, 28% of participants were anemic and 31% were borderline anemic. Iron and vitamin C consumption were negatively associated with Hb levels. Body mass index was marginally associated with Hb levels. Being born in a peri-urban setting, a proxy for early Westernized diet was associated with higher risk of anemia, suggesting developmental experience may play a role. Pregnant and lactating women had lower Hb levels than menstruating and menopausal women. Age, height, parity, and age at first pregnancy were not found to be statistically significant predictors of anemia. CONCLUSIONS: Iron deficiency represents a serious health concern for women, particularly pregnant ones. Our results suggest that both past and current nutritional ecology variables may be associated with the risk of anemia. These findings inform public health interventions, since reproductive history may be more difficult to modify than current diet.
Address Department of Anthropology, Yale University, New Haven, Connecticut, 05611
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1042-0533 ISBN Medium
Area Expedition Conference
Notes PMID:28101997 Approved no
Call Number ref @ user @ Serial 98030
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Author D'Alessandris, Q.G.; Biffoni, M.; Martini, M.; Runci, D.; Buccarelli, M.; Cenci, T.; Signore, M.; Stancato, L.; Olivi, A.; De Maria, R.; Larocca, L.M.; Ricci-Vitiani, L.; Pallini, R.
Title (down) The clinical value of patient-derived glioblastoma tumorspheres in predicting treatment response Type Journal Article
Year 2017 Publication Neuro-Oncology Abbreviated Journal Neuro Oncol
Volume 19 Issue 8 Pages 1097-1108
Keywords cancer stem cells; glioblastoma; radiotherapy; temozolomide; treatment outcome
Abstract Background: Advances from glioma stemlike cell (GSC) research, though increasing our knowledge of glioblastoma (GBM) biology, do not influence clinical decisions yet. We explored the translational power of GSC-enriched cultures from patient-derived tumorspheres (TS) in predicting treatment response. Methods: The relationship between TS growth and clinical outcome was investigated in 52 GBMs treated with surgical resection followed by radiotherapy and temozolomide (TMZ). The effect on TS of radiation (6 to 60 Gy) and of TMZ (3.9 muM to 1 mM) was related with patients' survival. Results: Generation of TS was an independent factor for poor overall survival (OS) and poor progression-free survival (PFS) (P < .0001 and P = .0010, respectively). Growth rate and clonogenicity of TS predicted poor OS. In general, TS were highly resistant to both radiation and TMZ. Resistance to TMZ was stronger in TS with high clonogenicity and fast growth (P < .02). Shorter PFS was associated with radiation LD50 (lethal dose required to kill 50% of TS cells) >12 Gy of matched TS (P = .0484). A direct relationship was found between sensitivity of TS to TMZ and patients' survival (P = .0167 and P = .0436 for OS and PFS, respectively). Importantly, values for TMZ half-maximal inhibitory concentration <50 muM, which are in the range of plasma levels achieved in vivo, identified cases with longer OS and PFS (P = .0020 and P = .0016, respectively). Conclusions: Analysis of TS holds translational relevance by predicting the response of parent tumors to radiation and, particularly, to TMZ. Dissecting the clonogenic population from proliferating progeny in TS can guide therapeutic strategies to a more effective drug selection and treatment duration.
Address Institute of Neurosurgery, Universita Cattolica del Sacro Cuore, Rome, Italy; Department of Hematology, Oncology and Molecular Medicine, Istituto Superiore di Sanita, Rome, Italy; Institute of Pathology, Universita Cattolica del Sacro Cuore, Rome, Italy; Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 1522-8517 ISBN Medium
Area Expedition Conference
Notes PMID:28204560 Approved no
Call Number ref @ user @ Serial 96607
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Author Lacovich, V.; Espindola, S.L.; Alloatti, M.; Pozo Devoto, V.; Cromberg, L.E.; Carna, M.E.; Forte, G.; Gallo, J.-M.; Bruno, L.; Stokin, G.B.; Avale, M.E.; Falzone, T.L.
Title (down) Tau Isoforms Imbalance Impairs the Axonal Transport of the Amyloid Precursor Protein in Human Neurons Type Journal Article
Year 2017 Publication The Journal of Neuroscience : the Official Journal of the Society for Neuroscience Abbreviated Journal J Neurosci
Volume 37 Issue 1 Pages 58-69
Keywords App; Alzheimer's; axonal transport; splicing; tau; tauopathies
Abstract Tau, as a microtubule (MT)-associated protein, participates in key neuronal functions such as the regulation of MT dynamics, axonal transport, and neurite outgrowth. Alternative splicing of exon 10 in the tau primary transcript gives rise to protein isoforms with three (3R) or four (4R) MT binding repeats. Although tau isoforms are balanced in the normal adult human brain, imbalances in 3R:4R ratio have been tightly associated with the pathogenesis of several neurodegenerative disorders, yet the underlying molecular mechanisms remain elusive. Several studies exploiting tau overexpression and/or mutations suggested that perturbations in tau metabolism impair axonal transport. Nevertheless, no physiological model has yet demonstrated the consequences of altering the endogenous relative content of tau isoforms over axonal transport regulation. Here, we addressed this issue using a trans-splicing strategy that allows modulating tau exon 10 inclusion/exclusion in differentiated human-derived neurons. Upon changes in 3R:4R tau relative content, neurons showed no morphological changes, but live imaging studies revealed that the dynamics of the amyloid precursor protein (APP) were significantly impaired. Single trajectory analyses of the moving vesicles showed that predominance of 3R tau favored the anterograde movement of APP vesicles, increasing anterograde run lengths and reducing retrograde runs and segmental velocities. Conversely, the imbalance toward the 4R isoform promoted a retrograde bias by a significant reduction of anterograde velocities. These findings suggest that changes in 3R:4R tau ratio has an impact on the regulation of axonal transport and specifically in APP dynamics, which might link tau isoform imbalances with APP abnormal metabolism in neurodegenerative processes. SIGNIFICANCE STATEMENT: The tau protein has a relevant role in the transport of cargos throughout neurons. Dysfunction in tau metabolism underlies several neurological disorders leading to dementia. In the adult human brain, two tau isoforms are found in equal amounts, whereas changes in such equilibrium have been associated with neurodegenerative diseases. We investigated the role of tau in human neurons in culture and found that perturbations in the endogenous balance of tau isoforms were sufficient to impair the transport of the Alzheimer's disease-related amyloid precursor protein (APP), although neuronal morphology was normal. Our results provide evidence of a direct relationship between tau isoform imbalance and defects in axonal transport, which induce an abnormal APP metabolism with important implications in neurodegeneration.
Address Instituto de Biologia y Medicina Experimental (IBYME-CONICET), Buenos Aires C1428ADN, Argentina
Corporate Author Thesis
Publisher Place of Publication Editor
Language English Summary Language Original Title
Series Editor Series Title Abbreviated Series Title
Series Volume Series Issue Edition
ISSN 0270-6474 ISBN Medium
Area Expedition Conference
Notes PMID:28053030 Approved no
Call Number ref @ user @ Serial 95902
Permanent link to this record