Recently Published - December 2012
Each month we would like to share the accomplishments of colleagues who have had studies published in medical and scientific journals. The Miner Library has pulled the following from PubMed within the last month, but we encourage researchers to share news of upcoming papers. If you have a paper scheduled to be published in the near future, please send details to firstname.lastname@example.org.
J Biol Chem. 2012 Nov 27. [Epub ahead of print]
Identification of microRNA-98 as a therapeutic target inhibiting prostate cancer growth and a biomarker induced by vitamin D.
Ting HJ, Messing J, Yasmin-Karin S, Lee YF.
University of Rochester Medical Center, United States.
The anti-tumor effect of vitamin D has been well recognized but its translational application is hindered by side effects induced by supra-physiological concentration of vitamin D required for cancer treatment. Thus, exploring vitamin D tumor suppressive functional mechanism can facilitate improvement of its clinical application. We screened miRNA profiles in response to vitamin D and found that a tumor suppressive miRNA, miR-98, is transcriptionally induced by 1alpha,25-dihydroxyvitamin D3 (1,25-VD) in LNCaP. Mechanistic dissection revealed that 1,25-VD-induced miR-98 is mediated through both a direct mechanism, enhancing the VDR binding response element in the promoter region of miR-98, and an indirect mechanism, down-regulating LIN-28 expression. Knockdown of miR-98 led to a reduction of 1,25-VD anti-growth effect and overexpression of miR-98 suppressed the LNCaP cells growth via inducing G2/M arrest. And CCNJ, a protein controlling cell mitosis, is down-regulated by miR-98 via targeting 3'-untranslated region of CCNJ. Interestingly, miR-98 levels in blood are increased upon 1,25-VD treatment in mice suggesting the biomarker potential of miR-98 in predicting 1,25-VD response. Together, the finding that growth inhibitive miR-98 is induced by 1,25-VD provides a potential therapeutic target for prostate cancer and a potential biomarker for 1,25-VD anti-tumor action.
PMID: 23188821 [PubMed - as supplied by publisher]
Dermatol Surg. 2012 Nov 16. doi: 10.1111/dsu.12029. [Epub ahead of print]
Malignant Tumors of the Penis.
Brady KL, Mercurio MG, Brown MD.
Department of Dermatology, University of Rochester, Rochester, New York.
Although penile cancer is rare in developed countries, it occurs more frequently in other parts of the world and causes significant morbidity and mortality.
To review the current literature on the pathogenesis, risk factors, clinical presentation, staging, and treatment of premalignant and malignant tumors of the penis.
MATERIALS AND METHODS:
A literature review using PubMed was conducted searching for articles on penile malignancies.
The majority of penile cancers are in situ or invasive squamous cell carcinomas, although other rare tumors of the penis occur, such as melanoma, basal cell carcinoma, extramammary Paget's disease, and soft tissue sarcomas.
Physicians should be aware of the risk factors and clinical presentation of penile malignancies because early diagnosis is essential in effective management and cure. Accurate staging is imperative for risk stratification and treatment planning. Depending on the type of tumor, size of tumor, location, staging, and grading, treatment modalities vary and may include topical chemotherapy, surgical excision, Mohs micrographic surgery, laser excision or ablation, systemic chemotherapy, and radiotherapy.
© 2012 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.
PMID: 23164051 [PubMed - as supplied by publisher]
Blood Cells Mol Dis. 2012 Nov 12. pii: S1079-9796(12)00191-X. doi: 10.1016/j.bcmd.2012.10.005. [Epub ahead of print]
A historical perspective on the development of the cytarabine (7days) and daunorubicin (3days) treatment regimen for acute myelogenous leukemia: 2013 the 40th anniversary of 7+3.
University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA. Electronic address: email@example.com.
This paper reviews the development of therapy for acute myelogenous leukemia that in 1973 led to the regimen of 7days of continuous intravenous arabinosylcytosine (cytarabine) and the first 3 concurrent days of intravenous daunorubicin, given the nickname "7+3." The state of leukemia treatment in the 1950s, 1960s and early 1970s is reviewed, the discovery of the two drugs in question described, and the introduction of clinical trials to reach an optimal regimen for their use delineated. During the 1950s, following World War Two and after a period of civil reconstitution, a national effort, facilitated by the U.S. Congress and federal investments in the National Cancer Institute, was initiated to enhance cancer therapy in the United States. The development of mouse models of leukemia and advances in understanding the structure and function of DNA and RNA and the process of cell proliferation provided new targets for drug development and new concepts for their use. The year, 2013, marks the 40th year that this protocol, 7+3, is the method of induction of remission for most patients with acute myelogenous leukemia. Its inadequacies also are made clear. Many patients with the disease die soon after diagnosis, and patients who have more unfavorable oncogenetic subtypes, intrinsically drug resistant cells, and greater intolerance to therapy make up the vast majority of the affected and few are cured. It is evident to all that new paradigms are needed if acute myelogenous leukemia is to be subdued in most patients with the disease.
Copyright © 2012 Elsevier Inc. All rights reserved.
PMID: 23154039 [PubMed - as supplied by publisher]
Hepatology. 2012 Nov 13. doi: 10.1002/hep.26135. [Epub ahead of print]
Targeting androgen receptor in bone marrow mesenchymal stem cells leads to better transplantation therapy efficacy in liver cirrhosis.
Huang CK, Lee SO, Lai KP, Ma WL, Lin TH, Tsai MY, Luo J, Chang C.
George Whipple Lab for Cancer Research, Departments of Pathology, Urology, Radiation Oncology, and The Wilmot Cancer Center, University of Rochester Medical Center, Rochester, NY 14642, USA.
Transplantation of bone marrow mesenchymal stem cells (BM-MSCs) has been considered as an alternative therapy, replacing liver transplantation in clinical trials, to treat liver cirrhosis, an irreversible disease that may eventually lead to liver cancer development. However, low survival rate of the BM-MSCs leading to un-satisfactory efficacy remains a major concern. Gender differences have been suggested in BM-MSCs therapeutic application, but the effect of the androgen receptor (AR), a key factor in male sexual phenotype, in this application is not clear. Using two liver cirrhosis mouse models induced by CCl4 or TAA, we show targeting AR in the BM-MSCs improves their self-renewal and migration potentials and increases paracrine effects to exert anti-inflammatory and anti-fibrotic actions to enhance liver repair. Mechanism dissection studies suggested that knocking out AR in BM-MSCs led to improved self-renewal and migration via alteration of the signaling of EGFR and MMP9, and resulted in suppression of infiltrating macrophages and hepatic stellate cells (HSC) activation through the modulation of IL1R/IL1Ra signaling. Therapeutic approaches using either AR-siRNA or the AR degradation enhancer, ASC-J9(®) , to target AR in BM-MSCs, all led to increased efficacy for repair liver, which may provide us a new way to battle liver cirrhosis. Conclusion: In summary, we provide this field a new process by which targeting AR, a key factor in male sexual phenotype, in BM-MSCs to improve the transplantation therapeutic efficacy for treating liver fibrosis may help us to better battle this irreversible disease in the future. (HEPATOLOGY 2012.).
Copyright © 2012 American Association for the Study of Liver Diseases.
PMID: 23150236 [PubMed - as supplied by publisher]
Ann Epidemiol. 2012 Nov 9. pii: S1047-2797(12)00396-1. doi: 10.1016/j.annepidem.2012.10.002. [Epub ahead of print]
The association between early life and adult body mass index and physical activity with risk of non-Hodgkin lymphoma: impact of gender.
Kelly JL, Fredericksen ZS, Liebow M, Shanafelt TD, Thompson CA, Call TG, Habermann TM, Macon WR, Wang AH, Slager SL, Cerhan JR.
School of Medicine and Dentistry, University of Rochester, Rochester, NY.
To evaluate the association of body mass index (BMI) and physical activity (PA) during adulthood and at the age of 18 years with risk of non-Hodgkin lymphoma (NHL).
We enrolled 950 newly diagnosed NHL patients and 1146 frequency-matched clinic-based controls. Height, weight, and PA (recent adult and at the age of 18 years) were self-reported. Odds ratios (ORs), 95% confidence intervals, and tests for trend were estimated using unconditional logistic regression adjusted for age, gender, and residence.
BMI at the age of 18 years was associated with an increased NHL risk (OR, 1.38 for highest vs. lowest quartile; p-trend = .0012), which on stratified analysis was specific to females (OR, 1.90; p-trend = .00025). There was no association of adult BMI with NHL risk. Higher PA in adulthood (OR, 1.03; p-trend = .85) or at the age of 18 years (OR, 0.88; 95% confidence interval, 0.72-1.07) was not associated with risk, but there was an inverse association for adult PA that was specific to females (OR, 0.71; p-trend = .039). Only BMI at the age of 18 years remained significantly associated with NHL risk when modeled together with PA in adulthood or at the age of 18 years. There was little evidence for heterogeneity in these results for the common NHL subtypes.
Early adult BMI may be of greatest relevance to NHL risk, particularly in females.
Copyright © 2012 Elsevier Inc. All rights reserved.
Mol Carcinog. 2012 Nov 9. doi: 10.1002/mc.21978. [Epub ahead of print]
Expression of UDP-glucuronosyltransferase 1A in bladder cancer: Association with prognosis and regulation by estrogen.
Izumi K, Li Y, Ishiguro H, Zheng Y, Yao JL, Netto GJ, Miyamoto H.
Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York.
Although UDP-glucuronosyltransferase 1A (UGT1A) plays an important role in preventing bladder cancer initiation by detoxifying carcinogenic compounds, its contribution to bladder cancer progression is poorly understood. We immunohistochemically stained for UGT1A in bladder specimens. UGT1A was positive in 130/145 (90%; 28 [19%] weak, 53 [37%] moderate, and 49 [34%] strong) urothelial neoplasms, which was significantly weaker than in matched non-neoplastic urothelial tissues (100/101 [99%]; 2 [2%] weak, 17 [17%] moderate, and 81 [80%] strong). Fifty (98%) of 51 low-grade/79 (99%) of 80 non-muscle-invasive tumors were immunoreactive to UGT1A, whereas 80 (85%) of 94 high-grade/51 (78%) of 65 muscle-invasive tumors were UGT1A-positive. Kaplan-Meier analysis showed strong associations between lower UGT1A expression versus the risk of recurrence in high-grade non-muscle-invasive tumors (P = 0.038) or disease-specific mortality in muscle-invasive tumors (P = 0.016). Multivariate analysis further revealed UGT1A loss as an independent prognosticator for disease-specific mortality in patients with muscle-invasive tumor (P = 0.010). Additionally, the expression of UGT1A was positively and negatively correlated with those of estrogen receptor-α and estrogen receptor-β, respectively. We then assessed UGT1A/Ugt1a levels in human cell lines/mouse tissues. 17β-Estradiol increased and decreased UGT1A expression in normal urothelium and bladder cancer lines, respectively, and an anti-estrogen abolished these effects. Ovariectomy in mice resulted in down-regulation of Ugt1a subtypes. These results suggest the involvement of UGT1A in not only bladder carcinogenesis but tumor progression. Moreover, UGT1A is likely regulated by estrogens in non-neoplastic urothelium versus bladder tumor in opposite manners, which could be underlying mechanisms of gender-specific differences in bladder cancer incidence and progression. © 2012 Wiley Periodicals, Inc.
Copyright © 2012 Wiley Periodicals, Inc.
PMID: 23143693 [PubMed - as supplied by publisher]