Detection of Methylated Circulating DNA as Noninvasive Biomarkers for Breast Cancer Diagnosis

Internationally, breast cancer is the most common female cancer, and is induced by a combination of environmental, genetic, and epigenetic risk factors. Despite the advancement of imaging techniques, invasive sampling of breast epithelial cells is the only definitive diagnostic procedure for patients with breast cancer. To date, molecular biomarkers with high sensitivity and specificity for the screening and early detection of breast cancer are lacking. Recent evidence suggests that the detection of methylated circulating cell-free DNA in the peripheral blood of patients with cancer may be a promising quantitative and noninvasive method for cancer diagnosis. Methylation detection based on a multi-gene panel, rather than on the methylation status of a single gene, may be used to increase the sensitivity and specificity of breast cancer screening. In this review, the results of 14 relevant studies, investigating the efficacy of cell-free DNA methylation screening for breast cancer diagnosis, have been summarized. The genetic risk factors for breast cancer, the methods used for breast cancer detection, and the techniques and limitations related to the detection of cell-free DNA methylation status, have also been reviewed and discussed. From this review, we conclude that the analysis of peripheral blood or other samples to detect differentially methylated cell-free DNA is a promising technique for use in clinical settings, and may improve the sensitivity of screening for both, early detection and disease relapse, and thus improve the future prognosis of patients with breast cancer.published_or_final_versio

Paternal low protein diet affects adult offspring cardiovascular and metabolic function in mice

Although the association between maternal periconceptional diet and adult offspring health is well characterised, our understanding of the impact of paternal nutrition at the time of conception on offspring phenotype remains poorly defined. Therefore, we determined the effect of a paternal preconception low protein diet (LPD on adult offspring cardiovascular and metabolic health in mice. Male C57BL/6 mice were fed either normal protein diet (NPD; 18% casein or LPD (9% casein for 7 wk before mating. At birth, a reduced male-to-female ratio (P = 0.03 and increased male offspring weight (P = 0.009 were observed in litters from LPD compared with NPD stud males with no differences in mean litter size. LPD offspring were heavier than NPD offspring at 2 and 3 wk of age (P <0.02. However, no subsequent differences in body weight were observed. Adult male offspring derived from LPD studs developed relative hypotension (decreased by 9.2 mmHg and elevated heart rate (P <0.05, whereas both male and female offspring displayed vascular dysfunction and impaired glucose tolerance relative to NPD offspring. At cull (24 wk, LPD males had elevated adiposity (P = 0.04, reduced heart-to-body weight ratio (P = 0.04, and elevated circulating TNF-α levels (P = 0.015 compared with NPD males. Transcript expression in offspring heart and liver tissue was reduced for genes involved in calcium signaling (Adcy, Plcb, Prkcb and metabolism (Fto in LPD offspring (P <0.03. These novel data reveal the impact of suboptimal paternal nutrition on adult offspring cardiovascular and metabolic homeostasis, and provide some insight into the underlying regulatory mechanisms

MiR-199a-5p confers tumor-suppressive role in triple-negative breast cancer

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Sustained and repeated response of relapsed acute promyelocytic leukaemia to intravenous or oral arsenic trioxide

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Unmanipulated bone marrow transplantation from one-Hla antigen mismatched siblings carries high transplant-related mortality compared with the Hla-identical counterparts

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Non-myeloablative allogeneic peripheral stem cell transplantation for multiple myeloma

Objective. To present an institution's 2-year experience of non-myeloablative allogeneic stem cell transplantation among Chinese patients. Design. Retrospective study. Setting. Bone marrow transplantation unit at a university hospital, Hong Kong. Patients. Ten patients with multiple myeloma who received non-myeloablative allogeneic stem cell transplantation between March 2000 and October 2002. Intervention. Fludarabine (90 mg/m 2) and total body irradiation (300 cGy) were given as conditioning regimens, followed by non-myeloablative allogeneic stem cell transplantation. Main outcome measures. Engraftment, regimen-related toxicity, treatment-related mortality (in the first 100 days), incidence of graft-versus-host disease, chimerism, disease response, and survival rate. Results. All 10 patients had active disease before transplantation. The donors were eight human leukocyte antigen-matched siblings, a mismatched sibling, and a matched daughter. Satisfactory engraftment before day 21 was achieved without early treatment-related mortality. Five patients developed full donor chimerism by day 28 and three other patients had 100% donor chimerism by day 100. Acute graft-versus-host disease developed in six patients (five with grade III and one with grade IV disease), and chronic graft-versus-host disease developed in eight patients (four with extensive disease). Complete remission and partial response were achieved in three and four patients, respectively. Three patients did not respond to treatment, and one case of relapse was observed. Only one patient, who had shown a partial response, received donor lymphocyte infusion; seven patients received thalidomide for graft-versus-host disease with or without graft-versus-myeloma effect. All patients were alive after a median follow-up of 1 year. Conclusion. Non-myeloablative allogeneic stem cell transplantation for multiple myeloma is effective, has low toxicity, and results in low treatment-related mortality. Studies of more cases with longer follow-up durations are required.published_or_final_versio

Intensive chemotherapy with peripheral blood stem cell (PBSC) support in the treatment of leukemia relapse after allogeneic bone marrow transplantation: clinical results and chimerism findings

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Sustained and repeated response of relapsed acute promyelocytic leukemia (APL) to arsenic therapy

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Oral arsenic trioxide in the treatment of relapsed acute promyelocytic leukaemia

INTRODUTION: Arsenic trioxide (As2O3) induces a remission in over 90% of patients with relapsed acute promyelocytic leukaemia (APL). To date, only the intravenous (i.v.) preparation of As2O3 has been used. We have recently developed an oral preparation of As2O3 that achieves blood levels of elemental arsenic comparable with those of i.v. As2O3 (Eur J Clin Pharmacol Oct 11, 2002 online). In this study, the efficacy and safety of oral As2O3 were …published_or_final_versio

Oral arsenic trioxide in the treatment of relapsed acute promyelocytic leukaemia

INTRODUTION: Arsenic trioxide (As2O3) induces a remission in over 90% of patients with relapsed acute promyelocytic leukaemia (APL). To date, only the intravenous (i.v.) preparation of As2O3 has been used. We have recently developed an oral preparation of As2O3 that achieves blood levels of elemental arsenic comparable with those of i.v. As2O3 (Eur J Clin Pharmacol Oct 11, 2002 online). In this study, the efficacy and safety of oral As2O3 were …published_or_final_versio