Abstract
Up to 85% of adult cancer survivors and 99% of adult survivors of childhood cancer live with an accumulation of chronic conditions, frailty, and/or cognitive impairments resulting from ...cancer and its treatment. Thus, survivors often show an accelerated development of multiple geriatric syndromes and need therapeutic interventions. To advance progress in this area, the National Cancer Institute convened the second of 2 think tanks under the auspices of the Cancer and Accelerated Aging: Advancing Research for Healthy Survivors initiative. Experts assembled to share evidence of promising strategies to prevent, slow, or reverse the aging consequences of cancer and its treatment. The meeting identified research and resource needs, including geroscience-guided clinical trials; comprehensive assessments of functional, cognitive, and psychosocial vulnerabilities to assess and predict age-related outcomes; preclinical and clinical research to determine the optimal dosing for behavioral (eg, diet, exercise) and pharmacologic (eg, senolytic) therapies; health-care delivery research to evaluate the efficacy of integrated cancer care delivery models; optimization of intervention implementation, delivery, and uptake; and patient and provider education on cancer and treatment-related late and long-term adverse effects. Addressing these needs will expand knowledge of aging-related consequences of cancer and cancer treatment and inform strategies to promote healthy aging of cancer survivors.
The Roll Back Malaria strategy recommends a combination of interventions for malaria control. Zanzibar implemented artemisinin-based combination therapy (ACT) for uncomplicated malaria in late 2003 ...and long-lasting insecticidal nets (LLINs) from early 2006. ACT is provided free of charge to all malaria patients, while LLINs are distributed free to children under age 5 y ("under five") and pregnant women. We investigated temporal trends in Plasmodium falciparum prevalence and malaria-related health parameters following the implementation of these two malaria control interventions in Zanzibar.
Cross-sectional clinical and parasitological surveys in children under the age of 14 y were conducted in North A District in May 2003, 2005, and 2006. Survey data were analyzed in a logistic regression model and adjusted for complex sampling design and potential confounders. Records from all 13 public health facilities in North A District were analyzed for malaria-related outpatient visits and admissions. Mortality and demographic data were obtained from District Commissioner's Office. P. falciparum prevalence decreased in children under five between 2003 and 2006; using 2003 as the reference year, odds ratios (ORs) and 95% confidence intervals (CIs) were, for 2005, 0.55 (0.28-1.08), and for 2006, 0.03 (0.00-0.27); p for trend < 0.001. Between 2002 and 2005 crude under-five, infant (under age 1 y), and child (aged 1-4 y) mortality decreased by 52%, 33%, and 71%, respectively. Similarly, malaria-related admissions, blood transfusions, and malaria-attributed mortality decreased significantly by 77%, 67% and 75%, respectively, between 2002 and 2005 in children under five. Climatic conditions favorable for malaria transmission persisted throughout the observational period.
Following deployment of ACT in Zanzibar 2003, malaria-associated morbidity and mortality decreased dramatically within two years. Additional distribution of LLINs in early 2006 resulted in a 10-fold reduction of malaria parasite prevalence. The results indicate that the Millennium Development Goals of reducing mortality in children under five and alleviating the burden of malaria are achievable in tropical Africa with high coverage of combined malaria control interventions.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Prostate cancer (PC) model systems that reflect the different disease stages are essential for studying the development and progression of PC and for testing new treatment modalities. This review ...summarizes the establishment and characterization of the PC346 progression model and compares it to other available human PC cell lines and xenografts.
The PC346 model was derived from the transurethral resection of a primary prostate tumor. Tumor samples were subcutaneously implanted into athymic mice, which resulted in the development of a series of xenografts from which in vitro cell cultures were established.
The PC346 panel includes sublines with hormone-response characteristics that range from androgen-sensitive to androgen-independent (AI) growth. In vivo and in vitro selection of androgen-sensitive lines under androgen-depleted conditions replicated the clinically relevant relapse phenomenon, and resulted in a series of modifications in the androgen-receptor (AR) pathway: AR mutation, overexpression, and downregulation.
The PC346 panel reproduces many biological characteristics of the different phases of clinical PC and the most common AR modifications observed in hormone-refractory tumors, being a valuable addition to the limited collection of available model systems.
Germline variants in the melanocortin 1 receptor gene (MC1R) might increase the risk of childhood and adolescent melanoma, but a clear conclusion is challenging because of the low number of studies ...and cases. We assessed the association of MC1R variants with childhood and adolescent melanoma in a large study comparing the prevalence of MC1R variants in child or adolescent patients with melanoma to that in adult patients with melanoma and in healthy adult controls.
In this retrospective pooled analysis, we used the M-SKIP Project, the Italian Melanoma Intergroup, and other European groups (with participants from Australia, Canada, France, Greece, Italy, the Netherlands, Serbia, Spain, Sweden, Turkey, and the USA) to assemble an international multicentre cohort. We gathered phenotypic and genetic data from children or adolescents diagnosed with sporadic single-primary cutaneous melanoma at age 20 years or younger, adult patients with sporadic single-primary cutaneous melanoma diagnosed at age 35 years or older, and healthy adult individuals as controls. We calculated odds ratios (ORs) for childhood and adolescent melanoma associated with MC1R variants by multivariable logistic regression. Subgroup analysis was done for children aged 18 or younger and 14 years or younger.
We analysed data from 233 young patients, 932 adult patients, and 932 healthy adult controls. Children and adolescents had higher odds of carrying MC1R r variants than did adult patients (OR 1·54, 95% CI 1·02-2·33), including when analysis was restricted to patients aged 18 years or younger (1·80, 1·06-3·07). All investigated variants, except Arg160Trp, tended, to varying degrees, to have higher frequencies in young patients than in adult patients, with significantly higher frequencies found for Val60Leu (OR 1·60, 95% CI 1·05-2·44; p=0·04) and Asp294His (2·15, 1·05-4·40; p=0·04). Compared with those of healthy controls, young patients with melanoma had significantly higher frequencies of any MC1R variants.
Our pooled analysis of MC1R genetic data of young patients with melanoma showed that MC1R r variants were more prevalent in childhood and adolescent melanoma than in adult melanoma, especially in patients aged 18 years or younger. Our findings support the role of MC1R in childhood and adolescent melanoma susceptibility, with a potential clinical relevance for developing early melanoma detection and preventive strategies.
SPD-Pilot/Project-Award-2015; AIRC-MFAG-11831.
Authors apart from NCGR and NCMA affiliates, FB and HMW (who performed 18S rRNA gene analyses), are community members who submitted samples for sequencing, including members of the advisory ...committee, but did not receive GBMF funds directly in support of these efforts. The number of people involved in this project at all levels was too great to allow all to be included in the author list, but in recognition of their tremendous efforts and their position as part of this community, we would like to thank Suzanne Strom (WWU), Mark Hildebrand (SIO); David Moreira, Purification Lopez Garcia (Université Paris-Sud); Adrian Reyes-Prieto (UNB); Bryndan P. Durham, Vanessa Varaljay (UGA); Behzad Imanian, Juan Saldarriaga, Jan Janouskovec, Greg Gavelis, Naoji Yabuki, Yingchun Gong (UBC); Charles Bachy, Sebastian Sudek, Hank Yu (MBARI); Chloe Deodato (UW); Chris Brown, Christien Laber, Kim Thamatrakoln, Brittany Schieler (Rutgers); Ida Orefice, Deepak Nanjappa (Stazione Zoologica Anton Dohrn); Roberto Sierra (University of Geneva); Rebecca Gast, Virginia Edgcomb, Sheean Haley, Harriet Alexander, David Beaudoin, Robert J. Olson (WHOI); Hollie M. Putnam, Michael P. Lesser (UH); Sheri Floge, Michael Preston (NCMA); Dreux Chappell, Amanda Burke, Gang Chen, Kelly Canesi, Andrea Drzewianowski, Joselynn Wallace, LeAnn Whitney, Kerry Whittaker, Amanda Montalbano (URI); Karen Pelletreau, Yunyun Zhuang, Huan Zhang, Yunyun Zhuang, (UCONN); Scott Lawrence (VUW); Min Park (LANL); Behzad Imanian, Jan Janouskovec, Juan Saldarriaga, Erick James, Greg Gavelis, Thierry Heger, Yoshihisa Hirakawa (UBC); K. Fraser Clark, Adam Acorn, Richard Cawthorn (UPEI); Raffaela M. Abbriano, Javier Paz Yepes, Christine N. Shulse (SIO); Kimberly deLong, Harry Masters (UNC-CH); Tom Savage (CSUS); Kendra Hayashi, Raphael Kudela (UCSC); Marianne Potvin, André Comeau (U Laval); Ewelina Rubin (SBU); Matthew Ashworth (UT Austin); Miguel Frada (Weizmann Institute of Science); Sandra Pucciarelli (University of Camerino); Dianna L. Berry, Matthew J. Harke, Yoonja Kang (SBU); Julia F. Hopkins, Eunsoo Kim, Naoko T. Onodera, Goro Tanifuji, Tommy Harding, Andrew Roger (Dalhousie University); Wei-Shu Hu (U Minnesota); William Rosado (U Puerto Rico); Jessica Grant, Dan Lahr (Smith College); Robert Molestina (American Type Culture Collection); Fran Van Dolah (NOAA); Anke Stüken, Russell Orr (U. Oslo); Simon Dittami (UiO); Sara Bender, Colleen Durkin, Gwenn Hennon, Julie Koester, Rhonda Morales, Irina Oleinikov, Micaela Parker, Francois Ribalet, Megan Schatz, Helena van Tol (UW); Robert Sanders (Temple); Karla Heidelberg (USC); Ramiro Logares (ICM, Barcelona); Anke Kremp (SYKE, Finland); Frederic Verret (IMBB); Vittorio Boscaro, Michele Castelli, Graziano Di Giuseppe, Fernando Dini, Graziano Di Giuseppe, Roberto Marangoni, Letizia Modeo (University of Pisa); Ian Probert, Priscillia Gourvil, Florence Le Gall (RCC); Marcus V. X. Senra (Federal University of Rio de Janeiro); Federico Buonanno, Claudio Ortenzi (University of Macerata); Susanna Theroux (JGI); Sophie Sanchez-Ferandin (UPMC); Sheree Yau (CNRS); Philipp Assmy, Sára Beszteri, Fabian Kilpert, Christine Klaas, Jan Meyer (AWI); Gurjeet Kohli (UTS); Sarah D'Adamo, Robert Jinkerson, Huiya Gu (CSM).
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patients with autoimmune polyendocrine syndrome type 1 often have autoantibodies against neurotransmitter synthesizing enzymes, including the pyridoxal phosphate-dependent enzymes glutamic acid ...decarboxylase and aromatic L-amino acid decarboxylase. Using a candidate approach, we have identified the histamine-synthesizing enzyme histidine decarboxylase, also pyridoxal phosphate dependent, as an autoantigen in this disorder. Anti-histidine decarboxylase antibodies reacting with in vitro translated antigen were found in 36/97 (37%) of autoimmune polyendocrine syndrome type 1 patients studied. The antibodies also reacted with the native enzyme in HMC-1 cell lysates and did not cross-react with the highly homologous aromatic L-amino acid decarboxylase. Anti-histidine decarboxylase antibodies were associated with a history of intestinal dysfunction (P = 0.017). Gastric and duodenal biopsies from a patient with anti-histidine decarboxylase antibodies were studied by immunohistochemistry. The oxyntic mucosa was found to lack the histamine producing enterochromaffin-like cells, suggestive of an autoimmune destruction. To our knowledge, this is the first report of autoantibodies against histidine decarboxylase and absence of gastric enterochromaffin-like cells.
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