Vincristine could partly suppress stromal support to T-ALL blasts during pegylated arginase I treatment

BACKGROUND: Relapsed T-lineage acute lymphoblastic leukemia (T-ALL) has been an incurable disease. Recent reports showed that an L-arginine depleting enzyme, pegylated arginase (BCT-100) may be effective against T-ALL cells. On the other hand, studies including ours had shown the symbiosis of ALL blasts and human mesenchymal stromal cells (hMSCs) in bone marrow microenvironment during L-asparaginase treatment. As L-asparaginase and BCT-100 both act by depleting lymphoid cells of specific amino acid, we hypothesized that hMSCs may also protect T-ALL blasts from BCT-100 treatment in co-culture and such protection may be abrogated by pre-treating hMSCs with vincristine (VCR). METHODS: XTT assay was used to test sensitivities of T-ALL cell lines and hMSCs to BCT-100. Apoptosis of T-ALL cell lines with or without BCT-100 treatment were tested by annexin V / propidium iodide (AV/PI) assay using flow cytometer. Western blotting was performed to analyze the expression of ornithine transcarbamylase (OTC), an enzyme involved in L-arginine metabolism which may account for BCT-100 resistance. RESULTS: hMSCs were resistant to BCT-100 while CCRF-CEM, Jurkat and MOLT-4 were very sensitive to it. hMSCs could protect all the three cell lines from BCT-100 treatment in transwell co-culture. All the 3 T-ALL cell lines were also found to be rescued by an L-arginine precursor citrulline, while the breakdown product of BCT-100, ornithine only had limited salvaging effect on CCRF-CEM but not Jurkat and MOLT-4. Both hMSCs and 3 T-ALL cell lines express citrulline synthesis enzyme, ornithine transcarbamylase (OTC) at basal level while only hMSCs could express OTC at relatively higher level under BCT-100 treatment. Treating hMSCs with vincristine before co-culturing with T-ALL could resume the cytotoxicity of BCT-100 to CCRF-CEM and MOLT-4 cells. CONCLUSIONS: Our results suggest a possible strategy to overcome resistance to BCT-100 from cancer microenvironments by suppressing hMSCs either in marrow or in the perivascular niche using vincristine.published_or_final_versio

Systemic effects of gut microbiota and its relationship with disease and modulation

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Orofacial complications in children undergoing cancer therapy in Hong Kong

Objectives. To investigate the orofacial complications in children undergoing cancer therapy and to increase their awareness of oral health. Methods. A randomly selected convenient sample of 46 children aged below 18 years undergoing combination chemotherapy for hematological malignancies or solid tumors at Queen Mary Hospital were recruited. Clinical examination and a parental questionnaire survey were performed. Parents were taught about oral health and received a talk that focused on the common oral complications of cancer therapy and their management. Results. Oral mucositis presenting as erythema or ulceration, mostly on the buccal mucosa, was present in approximately one third of children. Many had dry and cracked lips with varying degrees of xerostomia. Oral hygiene was generally unsatisfactory, although the majority brushed their teeth and 60% rinsed their mouth with antiseptics. The prevalence of opportunistic infection was nonetheless very low. Only one child presented with acute pseudomembranous candidiasis and none had herpes simplex infection. Most parents or caretakers reported that their children experienced pain in the mouth during cancer therapy. Many reported that their children had difficulty in speaking, pain while swallowing, salivary changes, and a dry mouth. Other oral complications included alteration of taste, bad breath, bleeding gums, and tooth decay. Conclusion. Oral mucositis was a common complication during cancer therapy together with pain in the oral cavity, poor oral hygiene, and dental caries. Professional oral care should be mandatory before, during, and after cancer therapy.published_or_final_versio

Health-related quality of life assessment for Hong Kong Chinese children with cancer

Key Messages 1. The direct measurement of quality of life in young children aged 30 to 72 months is feasible and valid. 2. An interactive storybook was developed to help inform young children with cancer of the medical procedures and consequences. The storybook had good construct, convergent, and criterion validity.published_or_final_versio

HIV-1 Tat dysregulation of KSHV induced immune response through the production of IL-8

Poster PresentationHuman immunodeficiency virus (HIV) causes acquired immunodeficiency syndrome (AIDS) and is a major health issue around the world. HIV is known to induce a number of pathological problems in AIDS patients via the transactivator (Tat) protein that is expressed and released by infected cells. One of the most important function of Tat is the dysregulation of the immune response. IL-8 is a chemokine known to be highly expressed in AIDS patients and Tat plays a major role in its production. IL-8 increases the HIV transmission and replication rate; and plays a role in Kaposi's sarcoma associated herpesvirus (KSHV) infection, which is a major opportunistic pathogen that AIDS patients are at risk to. KSHV is also known to induce the expression of IL-8 in patients, and IL-8 is known to assist tumour development by increasing angiogenesis. In our study, we investigated the role that Tat may have in manipulating the expression of IL-8 induced by KSHV in primary blood monocyte derived macrophages (PBMac). The results showed that pretreatment of PBMac with Tat inhibited the expression of IL-8 induced by KSHV by approximately 40%. We also found that Tat was able to inhibit the phosphorylation of STAT-1 induced by KSHV, and the inhibition of STAT-1 phosporylation was related to the expression of IL-8 induced by KSHV. In conclusion, we found that Tat was able to manipulate the expression of IL-8 induced by KSHV in macrophages, and this inhibition of IL-8 expression was regulated through the STAT-1 related pathways.published_or_final_versio

Effects of chelators (desferal, deferiprone & deferaairox) on the growth of klebsiella and aeromonas isolated from transfusion dependent thalassemia patients

Poster Presentation (Doctor’s Session)Infection is among the leading causes of death for thalassemia major patients. The known predisposing factors of infection include prior splenectomy, iron overload and use of iron chelator such as desferal (desferrioxamine). While encapsulated organisms frequently found in splenectomized patients were readily controlled by prophylactic vaccination and vigilant antibiotic treatment, ferrophilic organisms such as Yersinia and Klebsiella remains common among Thalassemic patients. The inductive iron overloaded environment favours the growth of these organisms but their growth is also affected by the environment temperature. For example, Yersinia infection is more prevalent in temperate regions and Klebsiella infection is commonly found in subtropical areas. Furthermore, the use of iron chelator in the form of desferal further aggravates the risk of Yersinia infection. It is because the iron membrane transport protein siderophore found in desferal can be adopted by the bacteria for iron acquisition. However, oral chelators such as deferiprone do not enhance growth of Yersinia in vitro or in vivo. In order to find out whether such observation can be extended to Klebsiella and Aeromona infection, in vitro culture assay using Klebsiella pneumoniae and Aeromonas hydrophila obtained directly from our transfusion dependent thalassaemic patients were performed. The growth rates of the bacteria under iron rich, iron poor with or without different chelators were assessed. The growth rates were analyzed by both: (1) optic density of bacterial broth; and (2) colony count by bacterial agar plate. We found that the growth of Klebsiella was marginally enhanced by desferal in vitro when compared to Yersinia. Such unfavourable effect was not found in either deferiprone or deferasirox in vitro. On the other hand, the growth of Aeromonas was not affected by the presence of any of the 3 chelators. Therefore, we suggested that factors other than desferal may account for the increase prevalence of Klebsiella and Aeromonas infection among Asian thalassemic patients. It also suggests that oral chelators are safe for thalassemic patients during febrile illness. Unlike desferal, withholding iron chelator during infectious period may not be mandatory. But care has to be exercised especially for patients on deferiprone, since neutropenia has to be ruled out during febrile illness. This project was supported by the Children's Thalassaemia Foundationspublished_or_final_versio

Urate oxidase for the prevention and treatment of tumour lysis syndrome in children with cancer

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Malignancies in Chinese patients with neurofibromatosis type 1

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Oral complications related to cancer therapy and bone marrow transplantation (BMT) amongst Chinese children

Abstract no. 271published_or_final_versio