Dutcher J.P.,New York Medical College |
Dutcher J.P.,Cancer Research Foundation of New York |
Wiernik P.H.,New York Medical College |
Wiernik P.H.,Cancer Research Foundation of New York |
And 4 more authors.
Familial Cancer | Year: 2016
The relationship between renal cell cancer (RCC) and hematologic malignancy (HM) in the same individual has been reported for more than 20 years, and is noted in SEER database studies. Family histories suggest a familial association as well. This study evaluates the occurrence of renal cell cancer and hematologic malignancies in individual patients and families, and the occurrence of age-of-onset anticipation among generations. Family history data from our familial patient registry, including more than 700 pedigrees of familial hematologic malignancies, and 700 patients with renal cell cancer, were reviewed. Twenty-six patients with a personal history of both RCC and HM are reported. Seventy four patients with RCC are noted to have 95 family members with HM. Consistent with past reports, there was male predominance among the patients with both diseases (71 %), and among the RCC patients’ relatives with HM (57 %). Also consistent was a predominance of lymphoid malignancies in those with both diseases (92 %) and in the HMs among family members of RCC patients (79 %). The majority (95 %) of HM relatives were first or second degree relatives of the patient with RCC. Thirty of 34 parent/child pairs demonstrated age of onset anticipation in which the child developed either disease at a younger age than the parent. The co-occurrence of RCC and HM in the same patient has been shown to be significantly greater than expected. Families also appear to have an increased association. The appearance of anticipation suggests that genetic factors may be significant in this association of RCC and HM. © 2016 Springer Science+Business Media Dordrecht
Reis L.M.,Medical College of Wisconsin |
Tyler R.C.,Medical College of Wisconsin |
Muheisen S.,Medical College of Wisconsin |
Salviati L.,University of Padua |
And 6 more authors.
Human Genetics | Year: 2013
Pediatric cataracts are observed in 1-15 per 10,000 births with 10-25 % of cases attributed to genetic causes; autosomal dominant inheritance is the most commonly observed pattern. Since the specific cataract phenotype is not sufficient to predict which gene is mutated, whole exome sequencing (WES) was utilized to concurrently screen all known cataract genes and to examine novel candidate factors for a disease-causing mutation in probands from 23 pedigrees affected with familial dominant cataract. Review of WES data for 36 known cataract genes identified causative mutations in nine pedigrees (39 %) in CRYAA, CRYBB1, CRYBB3, CRYGC (2), CRYGD, GJA8 (2), and MIP and an additional likely causative mutation in EYA1; the CRYBB3 mutation represents the first dominant allele in this gene and demonstrates incomplete penetrance. Examination of crystallin genes not yet linked to human disease identified a novel cataract gene, CRYBA2, a member of the βγ-crystallin superfamily. The p.(Val50Met) mutation in CRYBA2 cosegregated with disease phenotype in a four-generation pedigree with autosomal dominant congenital cataracts with incomplete penetrance. Expression studies detected cryba2 transcripts during early lens development in zebrafish, supporting its role in congenital disease. Our data highlight the extreme genetic heterogeneity of dominant cataract as the eleven causative/likely causative mutations affected nine different genes, and the majority of mutant alleles were novel. Furthermore, these data suggest that less than half of dominant cataract can be explained by mutations in currently known genes. © 2013 Springer-Verlag Berlin Heidelberg.
Loewen G.,Providence Regional Cancer Center |
Jayawickramarajah J.,Tulane University |
Zhuo Y.,Kadlec Regional Medical Center |
Shan B.,Washington State University
Journal of hematology & oncology | Year: 2014
Long non-coding RNAs (lncRNAs) govern fundamental biochemical and cellular processes. lncRNA HOX transcript antisense RNA (HOTAIR) represses gene expression through recruitment of chromatin modifiers. The expression of HOTAIR is elevated in lung cancer and correlates with metastasis and poor prognosis. Moreover, HOTAIR promotes proliferation, survival, invasion, metastasis, and drug resistance in lung cancer cells. Here we review the molecular mechanisms underlying HOTAIR-mediated aggressive phenotypes of lung cancer. We also discuss HOTAIR's potential in diagnosis and treatment of lung cancer, as well as the challenges of exploiting HOTAIR for intervention of lung cancer.
Brown A.,Kadlec Regional Medical Center
American Journal of Health-System Pharmacy | Year: 2012
Purpose. The use of anticoagulants for the prevention of venous thromboembolism (VTE) in hospitalized medical and surgical oncology patients is discussed. Summary. Hospitalized patients are often at risk for developing VTE, and risk is increased in patients who have cancer. Moreover, the incidence of VTE appears to be rising in hospitalized cancer patients, who have a 2.2-fold increased risk of mortality with a VTE compared with similar patients without VTE. The literature indicates that these patients are often inadequately anticoagulated, despite strong recommendations for prophylaxis. Although there are few studies that specifically address VTE prophylaxis in cancer patients, there are several large trials that have examined data in cancer subgroups. The trials have directly compared low-molecular-weight heparin (LMWH) with placebo, unfractionated heparin with LMWH, factor Xa inhibitor (fondaparinux) with placebo, and fondaparinux with LMWH. Three important guidelines provide current recommendations for VTE prophylaxis; the American Society of Clinical Oncology (ASCO), theNational Comprehensive Cancer Network (NCCN), and the American College of Chest Physicians (ACCP) recommend unfractionated heparin, LMWH, or fondaparinux for VTE prophylaxis when there are no contraindications. Pharmacists can play an essential role in ensuring that VTE prophylaxis is appropriate for individual patients. Interventions to improve compliance with guidelines are particularly important now due to financial incentives from qualityfocused organizations whose mandate is to decrease preventable mortality events in hospitals. Conclusion. Hospitalized patients with cancer often do not receive appropriate thromboprophylaxis. Guidelines from ASCO, ACCP, and NCCN recommend unfractionated heparin, an LMWH, or fondaparinux for VTE prophylaxis when there are no contraindications to such therapy. Copyright © 2012, American Society of Health-System Pharmacists, Inc. All rights reserved.
Smith R.P.,Maine Medical Center Research Institute |
Elias S.P.,Maine Medical Center Research Institute |
Borelli T.J.,Maine General Medical Center |
Missaghi B.,University of Calgary |
And 6 more authors.
Emerging Infectious Diseases | Year: 2014
We observed an increase in the ratio of pathogenic Babesia microti to B. odocoilei in adult Ixodes scapularis ticks in Maine. Risk for babesiosis was associated with adult tick abundance, Borrelia burgdorferi infection prevalence, and Lyme disease incidence. Our findings may help track risk and increase the focus on blood supply screening. © 2014, Emerging Infectious Diseases. All Rights Reserved.