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Quality of life in children with acute leukaemias: preliminary study using SF36 questionnaires

Zahilah, Z., Fadzil, A., Jamal, R.

Malaysian Journal of Paediatrics and Child Health, 2005;14(1):41-50.
MyJurnal

Life (QOL) of patients with childhood leukaemias presenting at the Hospital Universiti Kebangsaan Malaysia (HUKM). The objectives of this pilot study were 1) To assess the feasibility and applicability of assessing quality of life in leukaemia patients using the adult-based SF-36 questionnaire. 2) To compare the differences of QOL scores among patients based on gender and treatment status. The Short-Form-36 Health Survey (SF36) was used. The items in SF-36 were drawn from the original 245-item MOS questionnaire, which includes multi-item scales that measured the eight dimensions of quality of life namely physical function, role limitations (physical problems), bodily pain, general health, vitality, social functioning, role limitations (emotional problems) and mental health. Patients with acute leukaemias were chosen to participate in the study. Twenty-eight patients were recruited, twelve were males and 16 were females. Ten patients had completed therapy whilst 18 others were still undergoing treatment. The results showed that those patients off treatment have a better quality of life than those on chemotherapy. However, this was only significant with respect to the role limitation pertaining to physical problems. Although the use of the SF-36 was feasible, there were limitations especially in the younger age group.
Serobiological features and risk factors of hepatitis C virus infection in multiply transfused thalassaemia patients

Ghazali, F., Jamal, R., Zakaria, S.Z., Ismail, Z.H., Malik, Y.

Malaysian Journal of Paediatrics and Child Health, 1998;10(2):14-18.
MyJurnal

The two vital aspects of treatment for patients with tha-lassaemia are regular blood transfusions and iron chela-tion therapy. Unfortunately, the use of blood transfu-sions exposes these patients to the risks of acquiring transfusion related viral infections such as hepatitis C. Patients who acquire the hepatitis C virus (HCV) may develop chronic hepatitis and later on hepatocellular carcinoma. Hence, patients with thalassaemia should be regularly screened for the presence of HCV. We report here the results of a cross-sectional study conducted in a typical day-care centre for thalassaemics at the Hospital Universiti Kebangsaan Malaysia, involving 85 multiply transfused patients. We found that 19 patients (22.4%) were seropositive for HCV and two of them had positive HCV-RNA. Those who had started receiv-ing their transfusions before 1995, i.e. the year routine screening for HCV amongst blood donors were com-menced, and those who received transfusions 2-4 week-ly had a significantly higher risk of acquiring HCV infection.
Circular RNAs as Promising Biomarkers: A Mini-Review

Abu N, Jamal R

Front Physiol, 2016;7:355.
PMID: 27588005 DOI: 10.3389/fphys.2016.00355

The interest in circular RNAs has resurfaced in the past few years. What was considered as "junk" for nearly two decades is now one of the most interesting molecules. Circular RNAs are non-coding RNAs that are formed by back-splicing events and have covalently closed loops with no poly-adenylated tails. The regulation of circular RNAs is distinctive and they are selectively abundant in different types of tissues. Based on the current knowledge of circular RNAs, these molecules have the potential to be the "next big thing" especially as biomarkers for different diseases. This mini-review attempts to concisely look at the biology of circular RNAs, the putative functional activities, the prevalence of circular RNAs, and the possible role of circular RNA as biomarkers for diagnosis or measuring drug response.
Fulltext Thymoma: a case report and review of the literature

Hamidah, A., Poulsaeman, V., Suria, A.A., Zarina, A.L., Zulfiqar, M.A., Jamal, R.

Medicine & Health, 2010;5(1):49-54.
MyJurnal

Thymomas comprise about 1% of all mediastinal tumours and are rare in children. Typically, these tumours are aggressive, with a poor outcome. The current treatment of invasive thymoma is often multidisciplinary. We report a 16-year-old boy with invasive thymoma who was successfully treated with systemic chemotherapy, surgical resection and irradiation. The patient has been in continuous remission for 6 years without radiographic evidence of tumour recurrence.
Fulltext Minimal residual disease status in childhood acute lymphoblastic leukaemias by flow cytometry and their clinical and haematological features

Azma, R.Z., Zarina, A.L., Hamidah, A., Cheong, SK, Jamal, R., Hamidah, N.H.

Medicine & Health, 2010;5(1):22-33.
MyJurnal

Residual disease in patients with acute leukaemia indicates unfavorable prognosis. The evaluation of remission using flow cytometry allows a better estimation of minimal residual disease (MRD) after induction chemotherapy in childhood acute lymphoblastic leukaemia (ALL) cases. Patients in morphological marrow remission with presence of blast cells of less than 5%, may still have up to 1010 leukaemic cells. However with flow cytometric analysis, lower levels of the residual leukaemic cells (1 in 104 cells) can be detected and it can be used as a tool to predict relapse. This study compared the presenting clinical and haematological features of children with ALL and their residual disease status determined by flow cytometry. Analysis of their MRD status following remission-induction chemotherapy were done at day-28, week-12 and week-20. The cases were also followed up to five years, to determine their survival status. Their residual disease status by flow cytometric immunophenotyping was also compared with their bone marrow findings morphologically. Thirty-eight cases of precursor B-ALL in pediatric patients from UKM Medical Centre (UKMMC) were analyzed. There was no significant correlation between demographic, clinical and haematological features with MRD status at day-28. However, there was a significant correlation between MRD status by flow cytometry and by morphological marrow examination at week-12. Three cases showed persistent MRD findings until week-20 where two of the cases relapsed and died subsequently. Twenty four patients were still alive after five years of follow up.
Fulltext Peginterferon alfa-2b and ribavirin in thalassaemia/chronic hepatitis C virus-co-infected non-responder to standard interferon-based

Hamidah A, Thambidorai CR, Jamal R

Med J Malaysia, 2005 Oct;60(4):517-9.
PMID: 16570722

We describe a patient with HbE-beta thalassaemia and chronic hepatitis C virus infection (genotype 1a) who was treated successfully with peginterferon alfa-2b and ribavirin, following failure to respond to standard interferon and ribavirin therapy. She had sustained virological response for nearly 24 months after completing peginterferon alfa-2b and ribavirin therapy. Transfusion requirements were significantly increased during combination therapy due to ribavirin-induced haemolysis. The adverse effects of interferon were well tolerated. Combination therapy with peginterferon alfa-2b and ribavirin maybe a feasible treatment option for a subset of thalassaemia/HCV infected non-responders to standard interferon-based therapy.
Evaluation of two types of leukocyte removal filters on transfusion dependent thalassaemics

Jamal R, Mazeni NR, Hussin H

Malays J Pathol, 2000 Dec;22(2):79-83.
PMID: 16329539

The advent of leukocyte filters has enabled effective removal of leukocytes from certain blood products thus avoiding many adverse effects of blood transfusion. Many different materials have been incorporated into these filters to achieve >95% leukocyte removal. In this study we evaluated the efficacy of leukocyte removal of two different filters, using actual bedside transfusion settings involving patients with transfusion dependent thalassaemia. Fifty-one transfusion events were randomised to use either a polyurethane filter or a non-woven polyester filter. We found that the two filters achieved 98.4% and 96.2% leukocyte removal respectively (p = 0.022). We also found no significant correlation between pre-filtration white blood cell count and the volume transfused with the efficacy of leukodepletion. No untoward events or transfusion reactions were observed during the study.
Fulltext Cancer-Derived Exosomes as Effectors of Key Inflammation-Related Players

Othman N, Jamal R, Abu N

Front Immunol, 2019;10:2103.
PMID: 31555295 DOI: 10.3389/fimmu.2019.02103

Exosomes, a category of small lipid bilayer extracellular vesicles that are naturally secreted by many cells (both healthy and diseased), carry cargo made up of proteins, lipids, DNAs, and RNAs; all of which are functional when transferred to their recipient cells. Numerous studies have demonstrated the powerful role that exosomes play in the mediation of cell-to-cell communication to induce a pro-tumoral environment to encourage tumor progression and survival. Recently, considerable interest has developed in regard to the role that exosomes play in immunity; with studies demonstrating the ability of exosomes to either metabolically alter immune players such as dendritic cells, T cells, macrophages, and natural killer cells. In this review, we summarize the recent literature on the function of exosomes in regulating a key process that has long been associated with the progression of cancer-inflammation and immunity.
Fulltext Short stature and truncal shortening in transfusion dependent thalassemia patients: results from a thalassemia center in Malaysia

Hamidah A, Rahmah R, Azmi T, Aziz J, Jamal R

Southeast Asian J Trop Med Public Health, 2001 Sep;32(3):625-30.
PMID: 11944728

One of the major complications in patients with transfusion dependent thalassemia is growth impairment secondary to iron overload. We studied the growth status in 66 patients with beta-thalassemia major and HbE-beta thalassemia who were transfusion dependent, aged from 2 to 24 years, and 66 controls matched for sex and age. The prevalence of short stature in transfusion-dependent thalassemics was 54.5% compared to 4.5% in control group (p<0.001). Short stature was more prevalent in those above the age of 10 years in this study group (83.3% vs 16.7%). Transfusion dependent thalassemics with short stature were found to have significantly lower mean standing height standard deviation scores (SDS), sitting height SDS and subischial leg length SDS values (p<0.001). There was also a significant difference between the mean sitting height SDS and the mean subischial leg length SDS in our thalassemics with short stature, suggesting that the short stature was due to disproportionate truncal shortening. Serum ferritin levels were significantly higher in transfusion dependent thalassemics who were short compared to those who were of normal height (p = 0.002). However, the mean pre-transfusion hemoglobin levels did not differ significantly between patients with short stature and those with normal height (p = 0.216). The prevalence of short stature also did not differ significantly between those with beta-thalassemia major and those with HbE-beta thalassemia (p = 0.32). This study highlighted the importance of providing optimal treatment in these patients, including monitoring of growth parameters and optimizing iron chelation therapy.
Prolonged remission after splenectomy for refractory Evans syndrome--a case report and literature review

Hamidah A, Thambidorai CR, Jamal R

Southeast Asian J Trop Med Public Health, 2005 May;36(3):762-4.
PMID: 16124452

We describe a patient with Evans syndrome (autoimmune hemolytic anemia and autoimmune thrombocytopenia) who was refractory to steroids and intravenous immunoglobulin. She responded to splenectomy and has remained in clinical remission for 3 years. In the majority of cases, splenectomy rarely induces a durable remission but it may be beneficial in a small group of patients, hence should be considered as alternative therapy in the management of these patients.
Risk assessment and microbiological profile of infections in paediatric cancer patients with febrile neutropenia

Latiff Z, Zulkifli SZ, Jamal R

Malays J Pathol, 2002 Dec;24(2):83-9.
PMID: 12887165

Febrile neutropenia is a common and potentially fatal problem encountered in cancer patients undergoing chemotherapy. We carried out an observational study to evaluate the possible risk factors of developing fever amongst neutropenic children with an underlying malignancy. We also looked at the microbiological profile of causative pathogens in patients with febrile neutropenia. During a study period of 1 year, a total of 90 neutropenic episodes were recorded amongst 57 patients who were on treatment and follow-up during the study period. Multivariate analysis showed that factors such as chemotherapy status, underlying disease, existing central venous catheters, presenting white blood cell counts at chemotherapy, use of steroid therapy or hospitalisation at the onset of neutropenia, were not significant risk factors for developing fever during neutropenic episodes. Although the presence of a central venous catheter was associated with a higher risk of developing fever, it did not reach statistical significance (p=0.11). Of the 90 neutropenic episodes, 59 (65.6%) developed fever and 25 of these had positive blood cultures. The causative organisms include gram-negative bacteria (64%), gram positive bacteria (16%) and fungus (20%). Of the gram-negative organisms, Klebsiella spp. predominated (28%) with the extended spectrum beta-lactamase producing strain forming the majority (16%). Amongst those with fungaemia, Candida spp. and Candida tropicalis formed the majority (8% each) of the isolates.
Fulltext Treatment of chronic hepatitis C virus infection with interferon alfa and ribavirin: sustained response in two patients with transfusion dependent thalassaemia

Hamidah A, Yong JF, Zulkifli HI, Jamal R

Med J Malaysia, 2002 Sep;57(3):353-6.
PMID: 12440276

We describe two cases of transfusion dependent thalassaemics with chronic hepatitis C virus infection whom were treated successfully with interferon and ribavirin, following failure of response or relapse after an initial response to interferon monotherapy. They had sustained virological response for more than twelve months after completing therapy. Transfusion requirements were significantly increased during the combination therapy, probably due to ribavirin-induced haemolysis. Serum ferritin level decreased significantly during the treatment. Combination therapy with interferon alfa and ribavirin may be a feasible treatment option for some nonresponders to prior interferon monotherapy.
Probing the endogenous peptidomes of cancer for biomarkers: A new endeavor

Lee PY, Low TY, Jamal R

Adv Clin Chem, 2018 12 27;88:67-89.
PMID: 30612607 DOI: 10.1016/bs.acc.2018.10.004

The life span of cancer patients can be prolonged with appropriate therapies if detected early. Mass screening for early detection of cancer, however, requires sensitive and specific biomarkers obtainable from body fluids such as blood or urine. To date, most biomarker discovery programs focus on the proteome rather than the endogenous peptidome. It has been long-established that tumor cells and stromal cells produce tumor resident proteases (TRPs) to remodel the surrounding tumor microenvironment in support of tumor progression. In fact, proteolytic products of TRPs have been shown to correlate with malignant behavior. Being of low molecular weight, these unique peptides can pass through the endothelial barrier of the vasculature into the bloodstream. As such, the cancer peptidome has increasingly become a focus for biomarker discovery. In this review, we discuss on the various aspects of the peptidome in cancer biomarker research.
Fulltext miR-200c Regulation of Metastases in Ovarian Cancer: Potential Role in Epithelial and Mesenchymal Transition

Sulaiman SA, Ab Mutalib NS, Jamal R

Front Pharmacol, 2016;7:271.
PMID: 27601996 DOI: 10.3389/fphar.2016.00271

Among the gynecological malignancies, ovarian cancer is the most fatal due to its high mortality rate. Most of the identified cases are epithelial ovarian cancer (EOC) with five distinct subtypes: high-grade serous carcinoma, low-grade serous carcinoma, mucinous carcinoma, endometrioid carcinoma, and clear-cell carcinoma. Lack of an early diagnostic approach, high incidence of tumor relapse and the heterogenous characteristics between each EOC subtypes contribute to the difficulties in developing precise intervention and therapy for the patients. MicroRNAs (miRNAs) are single-stranded RNAs that have been shown to function as tumor suppressors or oncomiRs. The miR-200 family, especially miR-200c, has been shown to be implicated in the metastasis and invasion of ovarian carcinoma due to its functional regulation of epithelial-to-mesenchymal transition (EMT). This mini review is aimed to summarize the recent findings of the miR-200c functional role as well as its validated targets in the metastasis cascade of ovarian cancer, with a focus on EMT regulation. The potential of this miRNA in early diagnosis and its dual expression status are also discussed.
Fulltext Meta-analysis of gene expression in relapsed childhood B-acute lymphoblastic leukemia

Chow YP, Alias H, Jamal R

BMC Cancer, 2017 02 10;17(1):120.
PMID: 28183295 DOI: 10.1186/s12885-017-3103-1

BACKGROUND: Relapsed pediatric B-acute lymphoblastic leukemia (B-ALL) remains as the leading cause of cancer death among children. Other than stem cell transplantation and intensified chemotherapy, no other improved treatment strategies have been approved clinically. Gene expression profiling represents a powerful approach to identify potential biomarkers and new therapeutic targets for various diseases including leukemias. However, inadequate sample size in many individual experiments has failed to provide adequate study power to yield translatable findings. With the hope of getting new insights into the biological mechanisms underpinning relapsed ALL and identifying more promising biomarkers or therapeutic targets, we conducted a meta-analysis of gene expression studies involving ALL from 3 separate studies.
METHOD: By using the keywords "acute lymphoblastic leukemia", and "microarray", a total of 280 and 275 microarray datasets were found listed in Gene Expression Omnibus database GEO and ArrayExpress database respectively. Further manual inspection found that only three studies (GSE18497, GSE28460, GSE3910) were focused on gene expression profiling of paired diagnosis-relapsed pediatric B-ALL. These three datasets which comprised of a total of 108 matched diagnosis-relapsed pediatric B-ALL samples were then included for this meta-analysis using RankProd approach.
RESULTS: Our analysis identified a total of 1795 upregulated probes which corresponded to 1527 genes (pfp 1), and 1493 downregulated probes which corresponded to 1214 genes (pfp
The potential immune-eliciting cancer testis antigens in colorectal cancer

Chi Soh JE, Abu N, Jamal R

Immunotherapy, 2018 09;10(12):1093-1104.
PMID: 30185136 DOI: 10.2217/imt-2018-0044

The identification of cancer testis antigens (CTAs) has been an important finding in the search of potential targets for cancer immunotherapy. CTA is one of the subfamilies of the large tumor-associated antigens groups. It is aberrantly expressed in various types of human tumors but is absent in normal tissues except for the testis and placenta. This CTAs-restricted pattern of expression in human malignancies together with its potential immunogenic properties, has stirred the interest of many researchers to use CTAs as one of the ideal targets in cancer immunotherapy. To date, multiple studies have shown that CTAs-based vaccines can elicit clinical and immunological responses in different tumors, including colorectal cancer (CRC). This review details our current understanding of CTAs and CRC in regard to the expression and immunological responses as well as some of the critical hurdles in CTAs-based immunotherapy.
Simultaneous determination of 25-hydroxyvitamin D2 and 25-hydroxyvitamin D3 in human serum by ultra performance liquid chromatography: An economical and validated method with bovine serum albumin

Chin SF, Osman J, Jamal R

Clin Chim Acta, 2018 Oct;485:60-66.
PMID: 29935177 DOI: 10.1016/j.cca.2018.06.024

A simple and economical method has been developed for simultaneous determination of human serum 25-hydroxyvitamin D2 (25OHD2) and 25-hydroxyvitamin D3 (25OHD3) using Ultra Performance Liquid Chromatography (UPLC). Non-human matrix of 4% BSA was used to construct the calibration curve and in quality control samples' preparation to avoid interference of the endogenous 25-hydroxyvitamin D (25OHD) present in the human serum. 25OHD2, 25OHD3 and dodecanophenone (internal standard, IS) were separated on a CORTECS solid-core particle column and monitored by photodiode array detector at wavelength of 265 nm within five min run time. The relationship between 25OHD concentration and peak area ratio (25OHD:IS) was linear over the range of 12.5 - 200 nM with mean correlation coefficients (r2) >0.998. The limit of detection (LOD) for 25OHD2 and 25OHD3 was 3.00 nM and 3.79 nM, while the lower limit of quantification (LLOQ) was 9.11 nM and 11.48 nM, respectively. High repeatability was obtained for both isomers with intra-day CV% <5.6% and <5.3% for inter-day assay. This method was further tested with a commercial lyophilized serum control with an accuracy of 92.87-108.31% and applied on 214 human serum samples. In summary, this validated method with BSA can be reliably applied for routine quantification of 25OHD in adults.
Fulltext Piperacillin-tazobactam plus amikacin as an initial empirical therapy of febrile neutropenia in paediatric cancer patients

Hamidah A, Rizal AM, Nordiah AJ, Jamal R

Singapore Med J, 2008 Jan;49(1):26-30.
PMID: 18204765

We evaluated piperacillin-tazobactam in association with amikacin in the initial empirical therapy of febrile neutropenic children.
Fulltext Regulatory Non-coding RNAs Network in Non-alcoholic Fatty Liver Disease

Sulaiman SA, Muhsin NIA, Jamal R

Front Physiol, 2019;10:279.
PMID: 30941061 DOI: 10.3389/fphys.2019.00279

Non-alcoholic fatty liver disease (NAFLD) spectrum comprises simple steatosis and non-alcoholic steatohepatitis (NASH) that can lead to fibrosis and cirrhosis. The patients usually have no history of excessive alcohol consumption and other etiologies that can cause fatty liver. Understanding of the pathophysiology of NAFLD has revealed that non-coding RNAs (ncRNAs) play significant roles in modulating the disease susceptibility, pathogenesis and progression. Currently, the ncRNAs are grouped according to their sizes and their regulatory or housekeeping functions. Each of these ncRNAs has a wide range of involvement in the regulation of the genes and biological pathways. Here, we briefly review the current literature the regulatory ncRNAs in NAFLD pathogenesis and progression, mainly the microRNAs, long non-coding RNAs and circular RNAs. We also discuss the co-regulatory functions and interactions between these ncRNAs in modulating the disease pathogenesis. Elucidation of ncRNAs in NAFLD may facilitate the identification of early diagnostic biomarkers and development of therapeutic strategies for NAFLD.
Fulltext Simultaneous analysis of 25 trace elements in micro volume of human serum by inductively coupled plasma mass spectrometry (ICP-MS)

Mohammed Nawi A, Chin SF, Jamal R

Pract Lab Med, 2020 Jan;18:e00142.
PMID: 31720354 DOI: 10.1016/j.plabm.2019.e00142

INTRODUCTION: In recent years, trace elements have gained importance as biomarkers in many chronic diseases. Unfortunately, the requirement for sample volume increases with the extent of investigation either for diagnosis or elucidating the mechanism of the disease. Here, we describe the method development and validation for simultaneous determination of 25 trace elements (lithium [Li], beryllium [Be], magnesium [Mg], aluminium [Al], vanadium [V], chromium [Cr], manganese [Mn], iron [Fe], cobalt [Co], nickel [Ni], copper [Cu], zinc [Zn], gallium [Ga], arsenic [As], selenium [Se], rubidium [Rb], strontium [Sr], silver [Ag], cadmium [Cd], caesium [Cs], barium [Ba], mercury [Hg], thallium [Tl], lead [Pb], uranium [U]) using only 20 μL of human serum.
METHODS: Serum samples were digested with nitric acid and hydrochloric acid (ratio 1:1, v/v) and analysed by inductively coupled plasma-mass spectrometry (ICP-MS). Seronorm®, a human-derived serum control material was used as quality control samples.
RESULTS: The coefficient of variations for both intra- and inter-day precisions were consistently <15% for all elements. The validated method was later tested on 30 human serum samples to evaluate its applicability.
CONCLUSION: We have successfully developed and validated a precise and accurate analytical method for determining 25 trace elements requiring very low volume of human serum.

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