Cytokine-Induced NK-Like T Cells: From Bench to Bedside

Cytokine-induced killer (CIK) cells are polyclonal T effector cells generated when cultured under cytokine stimulation. CIK cells exhibit potent, non-MHC-restricted cytolytic activities against susceptible tumor cells of both autologous and allogeneic origins. Over the past 20 years, CIK cells have evolved from experimental observations into early clinical studies with encouraging preliminary efficacy towards susceptible autologous and allogeneic tumor cells in both therapeutic and adjuvant settings. This paper is our attempt to summarize the available published literature related to CIK cells. Looking into the future, we anticipate that the continuous therapeutic application of CIK cells will likely be developed along two major directions: overcoming the challenge to organize large prospective randomized clinical trials to define the roles of CIK cells in cancer immunotherapy and expanding its spectrum of cytotoxicity towards resistant tumor cells through experimental manipulations

Use of Valacyclovir for the treatment of cytomegalovirus antigenemia after hematopoietic stem cell transplantation

10.1186/s12878-015-0028-2BMC Hematology151

Characterization of Novel and Uncharacterized p53 SNPs in the Chinese Population – Intron 2 SNP Co-Segregates with the Common Codon 72 Polymorphism

Multiple single nucleotide polymorphisms (SNPs) have been identified in the tumor suppressor gene p53, though the relevance of many of them is unclear. Some of them are also differentially distributed in various ethnic populations, suggesting selective functionality. We have therefore sequenced all exons and flanking regions of p53 from the Singaporean Chinese population and report here the characterization of some novel and uncharacterized SNPs - four in intron 1 (nucleotide positions 8759/10361/10506/11130), three in intron 3 (11968/11969/11974) and two in the 3′UTR (19168/19514). Allelic frequencies were determined for all these and some known SNPs, and were compared in a limited scale to leukemia and lung cancer patient samples. Intron 2 (11827) and 7 (14181/14201) SNPs were found to have a high minor allele frequency of between 26–47%, in contrast to the lower frequencies found in the US population, but similar in trend to the codon 72 polymorphism (SNP12139) that shows a distribution pattern correlative with latitude. Several of the SNPs were linked, such as those in introns 1, 3 and 7. Most interestingly, we noticed the co-segregation of the intron 2 and the codon 72 SNPs, the latter which has been shown to be expressed in an allele-specific manner, suggesting possible regulatory cross-talk. Association analysis indicated that the T/G alleles in both the co-segregating intron 7 SNPs and a 4tagSNP haplotype was strongly associated increased susceptibility to lung cancer in non-smoker females [OR: 1.97 (1.32, 3.394)]. These data together demonstrate high SNP diversity in p53 gene between different populations, highlighting ethnicity-based differences, and their association with cancer risk

Developing Traditional Chinese Medicine in the Era of Evidence-Based Medicine: Current Evidences and Challenges

Evidence-based medicine (EBM), by integrating individual clinical expertise with the best available clinical evidence from systematic research, has in recent years been established as the standard of modern medical practice for greater treatment efficacy and safety. Traditional Chinese Medicine (TCM), on the other hand, evolved as a system of medical practice from ancient China more than 2000 years ago based on empirical knowledge as well as theories and concepts which are yet to be mapped by scientific equivalents. Despite the expanding TCM usage and the recognition of its therapeutic benefits worldwide, the lack of robust evidence from the EBM perspective is hindering acceptance of TCM by the Western medicine community and its integration into mainstream healthcare. For TCM to become an integral component of the healthcare system so that its benefits can be rationally harnessed in the best interests of patients, it is essential for TCM to demonstrate its efficacy and safety by high-level evidence in accordance with EBM, though much debate remains on the validity and feasibility of applying the EBM model on this traditional practice. This review aims to discuss the current status of research in TCM, explore the evidences available on its efficacy and safety, and highlight the issues and challenges faced in applying EBM to TCM

Natural Killer Cells for Therapy of Leukemia

Clinical application of natural killer (NK) cells against leukemia is an area of intense investigation. In human leukocyte antigen-mismatched allogeneic hematopoietic stem cell transplantations (HSCT), alloreactive NK cells exert powerful anti-leukemic activity in preventing relapse in the absence of graft-versus-host disease, particularly in acute myeloid leukemia patients. Adoptive transfer of donor NK cells post-HSCT or in non-transplant scenarios may be superior to the currently widely used unmanipulated donor lymphocyte infusion. This concept could be further improved through transfusion of activated NK cells. Significant progress has been made in good manufacturing practice (GMP)-compliant large-scale production of stimulated effectors. However, inherent limitations remain. These include differing yields and compositions of the end-product due to donor variability and inefficient means for cryopreservation. Moreover, the impact of the various novel activation strategies on NK cell biology and in vivo behavior are barely understood. In contrast, reproduction of the thirdparty NK-92 drug from a cryostored GMP-compliant master cell bank is straightforward and efficient. Safety for the application of this highly cytotoxic cell line was demonstrated in first clinical trials. This novel ‘off-theshelf’ product could become a treatment option for a broad patient population. For specific tumor targeting chimeric-antigen-receptor-engineered NK-92 cells have been designed

Evidence-Based Medicine for Traditional Chinese Medicine: Exploring the Evidence from a Western Medicine Perspective

This article reviews the evidence of clinical efficacy of Traditional Chinese Medicine (TCM). Extracts from single herbs have been studied by the conventional path of drug discovery to become useful drugs in Western Medicine (WM), testifying to the pharmacological activity of herbs used in TCM formulations. Complex formulations prescribed in accordance to the principles of TCM have been in use for centuries. Much effort has been made in proving its efficacy by the criteria of Evidence Based Medicine (EBM). Problems peculiar to adopting such an approach for TCM is discussed, including issues inherent to TCM as well as the lack of well conducted randomised controlled trial to provide robust evidence. As a result the purported efficacy of TCM treatment for many conditions could not be validated by EBM criteria. A selection of studies and meta-analyses providing convincing evidence to the efficacy of some TCM treatment is cited in this review. Improved methodology and reporting in TCM clinical trials will be essential in establishing the role of TCM in the management of certain defined diseases and complementing current Western medical treatment