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Tan H.H.,Blood Services Group | Wong C.Y.,Singapore General Hospital | Thike A.A.,Singapore General Hospital | Tan P.H.,Singapore General Hospital | Ho G.H.,The Surgical Center
Clinical Cancer Research | Year: 2013

Purpose: There is a quest for novel noninvasive diagnostic markers for the detection of breast cancer. The goal of this study is to identify circulating microRNA (miRNA) signatures using a cohort of Asian Chinese patients with breast cancer, and to compare miRNA profiles between tumor and serum samples. Experimental Design: miRNA from paired breast cancer tumors, normal tissue, and serum samples derived from 32 patients were comprehensively profiled using microarrays or locked nucleic acid real-time PCR panels. Serum samples from healthy individuals (n=22) were also used as normal controls. Significant serum miRNAs, identified by logistic regression, were validated in an independent set of serum samples from patients (n = 132) and healthy controls (n = 101). Results: The 20 most significant miRNAs differentially expressed in breast cancer tumors included miRNA (miR)-21, miR-10b, and miR-145, previously shown to be dysregulated in breast cancer. Only 7 miRNAs were overexpressed in both tumors and serum, suggesting that miRNAs may be released into the serum selectively. Interestingly, 16 of the 20 most significant miRNAs differentially expressed in serum samples were novel. MiR-1, miR-92a, miR-133a, and miR-133b were identified as the most important diagnostic markers, and were successfully validated; receiver operating characteristic curves derived from combinations of these miRNAs exhibited areas under the curves of 0.90 to 0.91. Conclusion: The clinical use of miRNA signatures as a noninvasive diagnostic strategy is promising, but should be further validated for different subtypes of breast cancers. © 2013 American Association for Cancer Research. Source


Koh M.B.C.,Blood Services Group | Lao Z.T.,Singapore General Hospital | Rhodes E.,St Georges Hospital and Medical School
Bailliere's Best Practice and Research in Clinical Obstetrics and Gynaecology | Year: 2013

The management of patients with pre-existing haematological diseases during pregnancy can be particularly challenging. The potential maternal and foetal toxicities from treatment regimens including chemotherapy for malignant haematological disorders mean that joint management between obstetricians and haematologists is essential for achieving good outcomes for both mother and baby. Patients with inherited or acquired disorders of haemostasis including platelets (essential thrombocythaemia) and coagulation (antiphospholipid syndrome) resulting in a pro-thrombotic state also require special consideration as pregnancy is generally considered to be a pro-thrombotic condition which could exacerbate the pre-existing disorder. The choice, timing and duration of anticoagulation or anti-platelet therapy require careful coordination during the antenatal, perinatal as well as postnatal periods to ensure that both maternal and foetal risks are taken into consideration. Pregnancy in women with sickle cell disease has long been identified as high risk with medical and pregnancy related risks being more common compared to women without it. A range of foetal risks have also been reported but improvement in outcomes has been seen with better obstetric and haematological care and the emphasis on multidisciplinary teamwork. The meticulous management of iron overload and risks associated with repeated blood transfusions extends into the care of pregnant women with other haemoglobinopathies like thalassemias. Crown Copyright © 2013. Source


Koh M.B.C.,St Georges Hospital and Medical School | Koh M.B.C.,Blood Services Group | Lao Z.T.,Singapore General Hospital | Rhodes E.,St Georges Hospital and Medical School
Best Practice and Research: Clinical Obstetrics and Gynaecology | Year: 2013

The management of patients with pre-existing haematological diseases during pregnancy can be particularly challenging. The potential maternal and foetal toxicities from treatment regimens including chemotherapy for malignant haematological disorders mean that joint management between obstetricians and haematologists is essential for achieving good outcomes for both mother and baby. Patients with inherited or acquired disorders of haemostasis including platelets (essential thrombocythaemia) and coagulation (antiphospholipid syndrome) resulting in a pro-thrombotic state also require special consideration as pregnancy is generally considered to be a pro-thrombotic condition which could exacerbate the pre-existing disorder. The choice, timing and duration of anticoagulation or anti-platelet therapy require careful coordination during the antenatal, perinatal as well as postnatal periods to ensure that both maternal and foetal risks are taken into consideration. Pregnancy in women with sickle cell disease has long been identified as high risk with medical and pregnancy related risks being more common compared to women without it. A range of foetal risks have also been reported but improvement in outcomes has been seen with better obstetric and haematological care and the emphasis on multidisciplinary teamwork. The meticulous management of iron overload and risks associated with repeated blood transfusions extends into the care of pregnant women with other haemoglobinopathies like thalassemias.© 2013 Published by Elsevier Ltd. All rights. Source


Leemhuis T.,University of Cincinnati | Padley D.,Human Cellular Therapy Laboratory Mayo Clinic | Keever-Taylor C.,Medical College of Wisconsin | Niederwieser D.,University of Leipzig | And 7 more authors.
Bone Marrow Transplantation | Year: 2014

The Graft Processing subcommittee of the Worldwide Network for Blood and Marrow Transplantation wrote this guideline to assist physicians and laboratory technologists with the setting up of a cell processing laboratory (CPL) to support a hematopoietic stem cell transplant program, thereby facilitating the start-up of a transplant program in a new location and improving patient access to transplantation worldwide. This guideline describes the minimal essential features of designing such a laboratory and provides a list of equipment and supply needs and staffing recommendations. It describes the typical scope of services that a CPL is expected to perform, including product testing services, and discusses the basic principles behind the most frequent procedures. Quality management (QM) principles specific to a CPL are also discussed. References to additional guidance documents that are available worldwide to assist with QM and regulatory compliance are also provided. © 2014 Macmillan Publishers Limited All rights reserved. Source


Suck G.,Blood Services Group | Oei V.Y.S.,Blood Services Group | Oei V.Y.S.,National University of Singapore | Linn Y.C.,Singapore General Hospital | And 5 more authors.
Experimental Hematology | Year: 2011

Objective: Interleukin (IL)-15 is a promising novel cytokine for natural killer (NK) cell activation and survival. We studied the effects of IL-15 compared to IL-2 on NK cells in long-term cultures for clinical translation. Materials and Methods: CD56 +CD3 - NK cells were expanded with IL-2 or IL-15 for 2 to 4 weeks within lymphokine-activated killer (LAK) cell cultures (LAK-NK) in serum-enriched AIM V or CellGro Stem Cell Growth Medium (SCGM). Cell growth, viability, and NK cell content were monitored and cytotoxicity assessed in a flow cytometric cytotoxicity assay. Results: IL-15 (100-1000 U/mL) could replace IL-2 (1000 U/mL) in AIM V cultures to achieve efficient LAK cell expansion. However, IL-15-stimulated LAK cells exceeded cytotoxicity of IL-2-stimulated LAK cells against K562, notably at later culture points. In the powerful CellGro SCGM, LAK cells expanded over 28 days an average of 905-fold ± 320-fold standard error of the mean (SEM) for IL-2 (500 U/mL) and 484-fold ± 98-fold SEM for IL-15 (500 U/mL), and NK cells within such LAK cultures expanded an average of 2320-fold ± 975-fold SEM for IL-2 and 1084-fold ± 309-fold SEM for IL-15. Importantly, such IL-15-activated LAK-NK cells retained enhanced cytotoxicity at later culture points against K562 as well. IL-15-stimulated effectors were also highly cytotoxic against hematological targets MOLT-4 and KU812 and nontoxic against autologous nonmalignant cells. Interestingly, IL-15-LAK-NK cells showed overall significant upregulation of the main activating and inhibitory NK cell receptors after long-term cytokine stimulation. Conclusions: Our results demonstrate the potential for IL-15 to support large-scale expansion of clinical-grade LAK-NK effectors, which could retain enhanced longer-term potency and preserve activation receptors in therapy of hematological malignancies. Protocols are readily clinically translatable. © 2011 ISEH - Society for Hematology and Stem Cells. Source

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