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Fulltext Primary Breast Sarcoma in a Middle Age Lady: A Rare Presentation

Adzwani.M, ang.X.J, Salleh MS, Norra.H, Aina.K.A

IIUM Medical Journal Malaysia, 2019;18(101):24-0.
MyJurnal

Sarcoma is an aggressive, malignant condition of a breast. It is a rare condition, which makes it difficult to diagnose at clinicopathological study. We are reporting a case of a primary breast sarcoma in a 54-year-old menopausal lady that came with painless fast growing right breast lump within 6 months of duration. Clinically, there was a huge mobile painless right breast lump without discoloration of skin noted. Both axilla and supraclavicular lymph node were not palpable. A mammogram showed large lobulated dense mass 8.3cm x 10.0cm in size occupying right upper outer quadrantcorrespond to BIRADS 4 lesion. A trucut biopsy reported as a papillary lesion. Repeated trucut biopsy reported as mesenchymal lesion with smooth muscle differentiation. With this histopathology report, she was diagnosed with mesenchymal tumor of right breast. She underwent an uneventful mastectomy. Histopathological examination of the surgical specimen reported as tumor with mesenchymal differentiation which requiring further confirmation by breast-endocrine pathologist as primary breast sarcoma. She was subjected to post op radiotherapy to the chest wall followed by adjuvant chemotherapy.
Fulltext Semisolid metal processing techniques for nondendritic feedstock production

Mohammed MN, Omar MZ, Salleh MS, Alhawari KS, Kapranos P

ScientificWorldJournal, 2013;2013:752175.
PMID: 24194689 DOI: 10.1155/2013/752175

Semisolid metal (SSM) processing or thixoforming is widely known as a technology that involves the formation of metal alloys between solidus and liquidus temperatures. For the procedure to operate successfully, the microstructure of the starting material must consist of solid near-globular grains surrounded by a liquid matrix and a wide solidus-to-liquidus transition area. Currently, this process is industrially successful, generating a variety of products with high quality parts in various industrial sectors. Throughout the years since its inception, a number of technologies to produce the appropriate globular microstructure have been developed and applied worldwide. The main aim of this paper is to classify the presently available SSM technologies and present a comprehensive review of the potential mechanisms that lead to microstructural alterations during the preparation of feedstock materials for SSM processing.
Fulltext Clinicopathological and Prognostic Characteristics of Malaysian Triple Negative Breast Cancer Patients Undergoing TAC Chemotherapy Regimen

Abdul Aziz AA, Md Salleh MS, Ankathil R

Int J Breast Cancer, 2020;2020:8424365.
PMID: 32308997 DOI: 10.1155/2020/8424365

Triple negative breast cancer (TNBC) is associated with aggressive tumour phenotype and early tumour relapse following diagnosis. Generally, clinicopathological features such as tumour size, patient's age at diagnosis, tumour histology subtypes, grade and stage, involvement of lymph nodes, and menopausal status are commonly used for predicting disease progression, prospects of recurrence, and treatment response. Prognostic value of clinicopathological features on Malaysian TNBC patients is limited. Thus, this study is aimed at investigating the association of clinicopathological features on disease-free survival (DFS) and overall survival (OS) of Malaysian TNBC patients undergoing TAC chemotherapy. Seventy-six (76) immunohistochemistry-confirmed TNBC patients were recruited. The clinicopathological features of TNBC patients were collected and recorded. Kaplan-Meier and log-rank followed by a Cox proportional hazard regression model were performed to evaluate the TNBC patients' survival. Out of 76 TNBC patients, 25 were chemoresistant and 51 were chemoresponders to the TAC chemotherapy regimen. The overall 5-year cumulative DFS and OS of TNBC patients were 63.5% and 76.3%, respectively. Multivariate Cox analysis demonstrated that medullary and metaplastic histology subtypes and positive axillary lymph node metastasis were significant prognostic factors associated with relapse with adjusted HR: 5.76, 95% CI: 2.35, 14.08 and adjusted HR: 3.55, 95% CI: 1.44, 8.74, respectively. Moreover, TNBC patients with medullary and metaplastic histology subtypes and positive axillary lymph node metastases had a higher risk to death than patients who had infiltrating ductal carcinoma and negative axillary lymph node metastasis (adjusted HR: 8.30, 95% CI: 2.38, 28.96 and adjusted HR: 6.12, 95% CI: 1.32, 28.42, respectively). Our results demonstrate the potential use of medullary and metaplastic histology subtype and positive axillary lymph node metastasis as a potential biomarker in predicting relapse and survival of the TNBC patients. This warrants further studies on intensification of chemotherapy and also identification and development of targeted therapy to reduce relapses and improve survival of TNBC patients.
Fulltext Microstructural evolution during DPRM process of semisolid ledeburitic D2 tool steel

Mohammed MN, Omar MZ, Syarif J, Sajuri Z, Salleh MS, Alhawari KS

ScientificWorldJournal, 2013;2013:828926.
PMID: 24223510 DOI: 10.1155/2013/828926

Semisolid metal processing is a relatively new technology that offers several advantages over liquid processing and solid processing because of the unique behaviour and characteristic microstructure of metals in this state. With the aim of finding a minimum process chain for the manufacture of high-quality production at minimal cost for forming, the microstructural evolution of the ledeburitic AISI D2 tool steel in the semisolid state was studied experimentally. The potential of the direct partial remelting (DPRM) process for the production of AISI D2 with a uniform globular microstructure was revealed. The liquid fraction was determined using differential scanning calorimetry. The microstructures of the samples were investigated using an optical microscope and a scanning electron microscope equipped with an energy dispersive spectroscopy analyser, while X-ray phase analysis was performed to identify the phase evolution and the type of carbides. Mechanical characterisation was completed by hardness measurements. The typical microstructure after DPRM consists of metastable austenite which was located particularly in the globular grains (average grain size about 50 μ m), while the remaining interspaces were filled by precipitated eutectic carbides on the grain boundaries and lamellar network.
Fulltext Comparison of antioxidant effects of honey, glibenclamide, metformin, and their combinations in the kidneys of streptozotocin-induced diabetic rats

Erejuwa OO, Sulaiman SA, Wahab MS, Salam SK, Salleh MS, Gurtu S

Int J Mol Sci, 2011;12(1):829-43.
PMID: 21340016 DOI: 10.3390/ijms12010829

Hyperglycemia-induced increase in oxidative stress is implicated in diabetic complications. This study investigated the effect of metformin and/or glibenclamide in combination with honey on antioxidant enzymes and oxidative stress markers in the kidneys of streptozotocin (60 mg/kg; intraperitoneal)-induced diabetic rats. Diabetic rats were randomized into eight groups of five to seven rats and received distilled water (0.5 mL); honey (1.0 g/kg); metformin (100 mg/kg); metformin (100 mg/kg) and honey (1.0 g/kg); glibenclamide (0.6 mg/kg); glibenclamide (0.6 mg/kg) and honey (1.0 g/kg); metformin (100 mg/kg) and glibenclamide (0.6 mg/kg); or metformin (100 mg/kg), glibenclamide (0.6 mg/kg) and honey (1.0 g/kg) orally once daily for four weeks. Malondialdehyde (MDA) levels, glutathione peroxidase (GPx) and superoxide dismutase (SOD) activities were significantly elevated while catalase (CAT) activity, total antioxidant status (TAS), reduced glutathione (GSH), and GSH:oxidized glutathione (GSSG) ratio was significantly reduced in the diabetic kidneys. CAT, glutathione reductase (GR), TAS, and GSH remained significantly reduced in the diabetic rats treated with metformin and/or glibenclamide. In contrast, metformin or glibenclamide combined with honey significantly increased CAT, GR, TAS, and GSH. These results suggest that combination of honey with metformin or glibenclamide might offer additional antioxidant effect to these drugs. This might reduce oxidative stress-mediated damage in diabetic kidneys.
Fulltext The Values of Receptor Activator Nuclear Kappa-B Ligand Expression in Stage III Giant Cell Tumor of the Bone

Ghani SA, Wan Ismail WF, Md Salleh MS, Yahaya S, Syahrul Fitri ZM

Indian J Orthop, 2018 2 9;52(1):31-34.
PMID: 29416167 DOI: 10.4103/ortho.IJOrtho_153_17

Background: Giant cell tumor (GCT) of bone is a benign locally aggressive primary bone tumor which is risky for local recurrences and pulmonary metastasis. Till date, there are still many uncertainties in predicting the aggressiveness of GCT. We aim to investigate whether receptor activator nuclear kappa-B ligand (RANKL) expression may determine the prognosis of the lesion.
Materials and Methods: We examined RANKL expression in 39 patients (21 males, 18 females) by immunohistochemistry. Four patients (10%) were presented with tumor recurrence, eight patients (20%) were complicated with lung metastasis, and two patients (5%) were presented with both recurrence and lung metastasis. Positive RANKL expression was assessed according to a scoring system evaluating the percentage of the immunostained epithelial area and the staining intensity. The cumulative score was calculated to determine the final score value. Data were analyzed using PASW version 18.0 and independent t-test between nonrecurrence/recurrence groups, and nonlung metastasis/lung metastasis groups. Significance was set at P < 0.05.
Results: Thirty-two patients (82%) scored 3 in RANKL-staining percentage from whole stromal cell population (>75%), 6 patients scored 2, and 1 patient scored 1. Nine patients (23%) scored 3 in RANKL-staining intensity (most intense), 19 patients (48%) scored 2, and 11 patients (29%) scored 1. Twenty six patients (67%) had strong RANKL expression (total score of 5-6), 12 patients (31%) showed moderate score (3-4) whereas only 1 patient (2%) showed weak RANKL expression. Together, the mean value of RANKL-staining percentage was 2.79, intensity 1.95 and the total score 4.77. The mean RANKL-staining percentage between recurrence and nonrecurrence groups was statistically significant (P = 0.009). There was no significant difference in the mean staining intensity and total score between nonrecurrence and recurrence groups, and staining percentage staining intensity and a total cumulative score of RANKL expression between lung metastasis and nonlung metastasis groups.
Conclusion: RANKL expression is generally high in Stage III GCT and is a reliable prognostic marker in predicting the risk of local recurrence however not in lung metastasis.
Comparison of Clinical Results and Pathological Examinations Between Locally Synthesized Bone-derived Hydroxyapatite and Medpor® Orbital Implants in Animal Models

Roslinah M, Wan Hitam WH, Md Salleh MS, Abdul Hamid SS, Shatriah I

Cureus, 2019 Jan 25;11(1):e3954.
PMID: 30956907 DOI: 10.7759/cureus.3954

We aimed to compare clinical and pathological reactions towards locally synthesized bovine bone derived from hydroxyapatite (bone docosahexaenoic acid (dHA)) and commercially available porous polyethylene (Medpor®, Porex Surgical Incorporation, Georgia, USA) orbital implants in animal models. An experimental study was performed on 14 New Zealand white rabbits. Group A (n=7) was implanted with bovine bone dHA and group B (n=7) was implanted with Medpor®. Clinical examinations were performed on Days 1, 7, 14, 28, and 42 post-implantation. The implanted eyes were enucleated on Day 42 and were sent for pathological evaluation. Serial clinical examinations included urine color and odor; feeding and physical activity demonstrated normal wellbeing in all the subjects. Localized minimal infection was observed in both groups during the first two weeks following implantation, and the subjects responded well to topical moxifloxacin. Both groups exhibited evidence of wound breakdown. No signs of implant migration or extrusion were observed in either group. The histopathological examination revealed no statistically significant difference in inflammatory cell reactions and fibrovascular tissue maturation between both types of implants. However, all (100%) of the bovine bone dHA implants displayed complete fibrovascular ingrowth compared to Medpor® implants (57.1%) at six weeks post-implantation (p=0.001). In conclusion, bovine bone dHA and Medpor® orbital implants were well-tolerated clinically and displayed similar inflammatory reactions and fibrovascular tissue maturation. Locally synthesized bovine bone dHA orbital implants displayed significantly greater complete fibrovascular ingrowth in comparison with Medpor® implants.
ADAM9 Expression in Uterine Cervical Cancer and Its Associated Factors

Mohd Isa SA, Md Salleh MS, Ismail MP, Hairon SM

Asian Pac J Cancer Prev, 2019 Apr 29;20(4):1081-1087.
PMID: 31030477

Background: Cervical cancer is a preventable disease caused by human papillomaviruses. It is the third most
common cancer to occur in women of reproductive age. The ADAM9 protein plays a role in basement membrane
degradation and tumour metastasis in certain types of tumour. Thus, it has the potential to become a new targeted
therapy. The objective of this study was to investigate ADAM9 expression in cervical cancer and to determine the
factors associated with ADAM9-positive expression. Methods: This cross-sectional study was conducted in Hospital
Universiti Sains Malaysia (HUSM) Kelantan, Malaysia from December 2010 to December 2012. Histological slides
obtained from 95 cervical cancer cases diagnosed and/or treated in HUSM from 2000 to 2010 were analysed. The
ADAM9 immunostain was then performed on the paraffin blocks. The statistical data entry and analysis were done
using SPSS version 18.0. Multiple logistic regression analysis was performed to determine the factors associated with
ADAM9-positive expression. Result: Of the 95 cervical cancer patients included in the study, 72 (75.8%) patients showed
positive ADAM9 expression. The mean age of the patients was 53.89 (10.83) years old. Squamous cell carcinoma was
the most common type of cervical cancer (n = 67, 70.5%). Factors that showed a statistically significant association
with ADAM9-positive expression were tumour size (adjusted odds ratio [adj. OR]: 1.08; 95% confidence interval
[CI]: 1.02, 1.13; p = 0.004), distant metastasis (adj. OR: 12.82; 95% CI: 1.91, 86.13; p = 0.009) and the histological
type of cervical cancer (i.e. squamous cell carcinoma) (adj. OR: 7.39; 95% CI: 1.42, 38.51; p = 0.017). Conclusion:
The ADAM9 immunostain was consistently positive in malignant cells. Thus, ADAM9 expression can be used as a
prognostic/therapeutic indicator in aiding clinician decision-making regarding patient treatment (targeted therapy).
Fulltext Early Development of Fig (Ficus carica L.) Root and Shoot Using Different Propagation Medium and Cutting Types

Shamsuddin MS, Shahari R, Amri CNAC, Tajudin NS, Mispan MR, Salleh MS

Trop Life Sci Res, 2021 Mar;32(1):83-90.
PMID: 33936552 DOI: 10.21315/tlsr2021.32.1.5

This study aimed at determining the effects of propagation medium and cutting types on the early growth performance of fig (Ficus carica L.) root and shoot. The experiment was conducted at the Glasshouse and Nursery Complex (GNC), International Islamic University Malaysia (IIUM). The split-plot design was employed with the main plot (propagation medium) and sub-plot (types of cutting). The propagation medium were sand:topsoil (1:3) (M1), topsoil:peat:sawdust (1:1:1) (M2) and peat:perlite (1:1) (M3). Two types of cutting were semi-hardwood (C1) and hardwood (C2). As a result, there were a significant effect of propagation medium on measured parameters. This study revealed that the most effective propagation medium and cutting types for the propagation of fig were a combination of peat and perlite at 1:1 ratio (M3) and hardwood cutting (C2), respectively as evidenced by significantly higher root and shoot growth quality as compared to other treatments.
Microcalcification in the arterial wall and its relationship to the ultrasound criteria of maturation of the arteriovenous fistula

Tang WJ, Adnan AS, Md Salleh MS, Mat Saad AZ

J Vasc Access, 2018 Oct 01.
PMID: 30269637 DOI: 10.1177/1129729818775359

INTRODUCTION: A functioning and reliable arteriovenous fistula is a lifeline for individuals suffering from chronic kidney disease. The success and failure to arteriovenous fistula maturation have been frequently related to patient and surgeon factors.
METHOD: In total, 138 participants with stage IV and V chronic kidney disease were included in this prospective observational study. Preoperative vascular mapping using ultrasound was performed to evaluate the condition and size of the vessels to fulfil the inclusion criteria. Intraoperatively, the vessel size was measured prior to anastomosis under magnified view. A specimen from the arterial wall of 5 mm in diameter was obtained from the arterotomy for histopathology assessment. Arteriovenous maturation was assessed at 6 weeks with the guidance of the ultrasound criteria of rule of sixes.
RESULTS: From the total of 138 participants, 110 participants (79.7%) had matured arteriovenous fistula in 6 weeks. The mean size of the artery measured intraoperatively was 3.82 ± 1.33 mm and the vein was 4.05 ± 1.20 mm. Microcalcification in the arterial media which was hypothesised to be the cause of the arteriovenous fistula failure was insignificant, with a p value of 0.115. Despite having atherosclerosis in the artery, 83.3% of the arteriovenous fistula matured.
CONCLUSION: Microcalcification and atherosclerosis are frequently seen in the arteries of chronic kidney disease patients, but they do not explain arteriovenous fistula non-maturation.
Fulltext Genetic Association of CYP1B1 4326 C>G Polymorphism with Disease-Free Survival in TNBC Patients Undergoing TAC Chemotherapy Regimen

Abdul Aziz AA, Md Salleh MS, Yahya MM, Zakaria AD, Ankathil R

Asian Pac J Cancer Prev, 2021 Apr 01;22(4):1319-1324.
PMID: 33906328 DOI: 10.31557/APJCP.2021.22.4.1319

BACKGROUND: Triple negative breast cancer (TNBC) which is treated with taxane, adriamycin and cyclophosphamide (TAC) chemotherapy regimen show variation in treatment response. CYP1B1 4326 C>G polymorphism has been implicated in contributing to the differences in treatment response in various types of cancers.
AIM: The objective of the present study was to investigate whether this polymorphism modulate the risk of disease recurrence in TNBC patients undergoing TAC chemotherapy regimen.
METHODS: Blood samples of 76 immunohistochemistry confirmed TNBC patients were recruited. The genotyping of CYP1B1 4326 C>G polymorphism was carried out using PCR-RFLP technique. The genotype patterns were categorized into homozygous wildtype, heterozygous and homozygous variant. Kaplan-Meier analysis followed by Cox proportional hazard regression model were performed to evaluate the TNBC patients' recurrence risk.
RESULTS: Out of 76 TNBC patients, 25 (33.0%) showed disease recurrence after one-year evaluation. Kaplan Meier analysis showed that TNBC patients who are carriers of CYP1B1 4326 GG variant genotypes (37.0%) had a significantly lower probability of disease-free rates as compared to TNBC patients who are carriers of CYP1B1 4326 CC/CG genotypes (71.0%). Univariate and multivariate Cox analysis demonstrated that TNBC patients who carried CYP1B1 4326 GG variant genotype had a significantly higher risk of recurrence with HR: 2.50 and HR: 4.18 respectively, even after adjustment as compared to TNBC patients who were carriers of CYP1B1 4326 CC and CG genotypes.
CONCLUSION: Our results demonstrate the potential use of CYP1B1 4325 GG variant genotype as a candidate biomarker in predicting risk of recurrence in TNBC patients undergoing TAC chemotherapy regimen.
Fulltext Glibenclamide or metformin combined with honey improves glycemic control in streptozotocin-induced diabetic rats

Erejuwa OO, Sulaiman SA, Wahab MS, Sirajudeen KN, Salleh MS, Gurtu S

Int J Biol Sci, 2011 Mar 14;7(2):244-52.
PMID: 21448302 DOI: 10.7150/ijbs.7.244

Diabetes mellitus is associated with deterioration of glycemic control and progressive metabolic derangements. This study investigated the effect of honey as an adjunct to glibenclamide or metformin on glycemic control in streptozotocin-induced diabetic rats. Diabetes was induced in rats by streptozotocin. The diabetic rats were randomized into six groups and administered distilled water, honey, glibenclamide, glibenclamide and honey, metformin or metformin and honey. The animals were treated orally once daily for four weeks. The diabetic control rats showed hypoinsulinemia (0.27 ± 0.01 ng/ml), hyperglycemia (22.4 ± 1.0 mmol/L) and increased fructosamine (360.0 ± 15.6 µmol/L). Honey significantly increased insulin (0.41 ± 0.06 ng/ml), decreased hyperglycemia (12.3 ± 3.1 mmol/L) and fructosamine (304.5 ± 10.1 µmol/L). Although glibenclamide or metformin alone significantly (p < 0.05) reduced hyperglycemia, glibenclamide or metformin combined with honey produced significantly much lower blood glucose (8.8 ± 2.9 or 9.9 ± 3.3 mmol/L, respectively) compared to glibenclamide or metformin alone (13.9 ± 3.4 or 13.2 ± 2.9 mmol/L, respectively). Similarly, glibenclamide or metformin combined with honey produced significantly (p < 0.05) lower fructosamine levels (301.3 ± 19.5 or 285.8 ± 22.6 µmol/L, respectively) whereas glibenclamide or metformin alone did not decrease fructosamine (330.0 ± 29.9 or 314.6 ± 17.9 µmol/L, respectively). Besides, these drugs or their combination with honey increased insulin levels. Glibenclamide or metformin combined with honey also significantly reduced the elevated levels of creatinine, bilirubin, triglycerides, and VLDL cholesterol. These results indicate that combination of glibenclamide or metformin with honey improves glycemic control, and provides additional metabolic benefits, not achieved with either glibenclamide or metformin alone.
Antioxidant protection of Malaysian tualang honey in pancreas of normal and streptozotocin-induced diabetic rats

Erejuwa OO, Sulaiman SA, Wahab MS, Sirajudeen KN, Salleh MS, Gurtu S

Ann Endocrinol (Paris), 2010 Sep;71(4):291-6.
PMID: 20398890 DOI: 10.1016/j.ando.2010.03.003

Glucotoxicity contributes to beta-cell dysfunction through oxidative stress. Our previous study demonstrated that tualang honey ameliorated renal oxidative stress and produced hypoglycemic effect in streptozotocin (STZ)-induced diabetic rats. This present study investigated the hypothesis that hypoglycemic effect of tualang honey might partly be due to protection of pancreas against oxidative stress. Diabetes was induced by a single dose of STZ (60 mg/kg; ip). Diabetic rats were randomly divided into two groups and administered distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). Similarly, two groups of non-diabetic rats received distilled water (0.5 ml/d) and tualang honey (1.0 g/kg/d). The animals were treated orally for 28 days. At the end of the treatment period, the honey-treated diabetic rats had significantly (p<0.05) reduced blood glucose levels [8.8 (5.8)mmol/L; median (interquartile range)] compared with the diabetic control rats [17.9 (2.6)mmol/L]. The pancreas of diabetic control rats showed significantly increased levels of malondialdehyde (MDA) and up-regulation of superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities. Catalase (CAT) activity was significantly reduced while glutathione-S-transferase (GST) and glutathione reductase (GR) activities remained unchanged in the pancreas of diabetic rats. Tualang honey significantly (p<0.05) reduced elevated MDA levels. Honey treatment also restored SOD and CAT activities. These results suggest that hypoglycemic effect of tualang honey might be attributed to its antioxidative effect on the pancreas.
Fulltext Association of ABCG2 Polymorphisms on Triple Negative Breast Cancer (TNBC) Susceptibility Risk

Hao Ing Y, Md Salleh MS, Yahya MM, Ankathil R, Abdul Aziz AA

Asian Pac J Cancer Prev, 2023 Nov 01;24(11):3891-3897.
PMID: 38019248 DOI: 10.31557/APJCP.2023.24.11.3891

OBJECTIVE: The aim of this study was to elucidate the association of ATP-binding cassette super-family G member 2 (ABCG2) gene polymorphisms with individual susceptibility to Triple Negative Breast Cancer (TNBC) as well as clinicopathological variables in TNBC patients. Two common polymorphisms in Asian population, ABCG2 34 G>A and 421 C>A was selected in this study.
METHODS: Blood samples were collected from 75 TNBC patients and 83 controls. Genomic DNA was extracted from blood samples and the SNP genotyping was performed by using PCR-RFLP technique. The genotypes were characterized and grouped into homozygous wildtype, heterozygote and homozygous variant based on the band size. The result was subjected to statistical analysis.
RESULTS: The A allele and AA genotype of ABCG2 421 C>A had OR of 3.011 (p=0.003, 95% CI: 1.417-6.398) and 9.042 (p=0.011, 95% CI: 1.640-49.837), to develop advanced staging carcinoma respectively. The AA genotype of ABCG2 421 C>A polymorphism was also associated with metaplastic and medullary carcinoma with an OR of 6.429 (p=0.018, 95% CI: 1.373-30.109). A significant association was also found in haplotype 34G/421A of ABCG2 with advanced cancer staging as well as metaplastic and medullary carcinoma with OR of 2.347 (p=0.032, 95% CI: 1.010-5.560) and 2.546 (p=0.008, 95% CI: 1.005-6.447), respectively. Conclusion: The present study suggests that ABCG2 421 C>A polymorphism was associated with metaplastic and medullary histology and advanced cancer staging in TNBC patients.
Fulltext Antioxidant protective effect of glibenclamide and metformin in combination with honey in pancreas of streptozotocin-induced diabetic rats

Erejuwa OO, Sulaiman SA, Wahab MS, Salam SK, Salleh MS, Gurtu S

Int J Mol Sci, 2010 May 05;11(5):2056-66.
PMID: 20559501 DOI: 10.3390/ijms11052056

Hyperglycemia exerts toxic effects on the pancreatic beta-cells. This study investigated the hypothesis that the common antidiabetic drugs glibenclamide and metformin, in combination with tualang honey, offer additional protection for the pancreas of streptozotocin (STZ)-induced diabetic rats against oxidative stress and damage. Diabetes was induced in male Sprague Dawley rats by a single dose of STZ (60 mg/kg; ip). Diabetic rats had significantly elevated levels of lipid peroxidation (TBARS), up-regulated activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) while catalase (CAT) activity was significantly reduced. Glibenclamide and metformin produced no significant effects on TBARS and antioxidant enzymes except GPx in diabetic rats. In contrast, the combination of glibenclamide, metformin and honey significantly up-regulated CAT activity and down-regulated GPx activity while TBARS levels were significantly reduced. These findings suggest that tualang honey potentiates the effect of glibenclamide and metformin to protect diabetic rat pancreas against oxidative stress and damage.
Fulltext Differential responses to blood pressure and oxidative stress in streptozotocin-induced diabetic Wistar-Kyoto rats and spontaneously hypertensive rats: effects of antioxidant (honey) treatment

Erejuwa OO, Sulaiman SA, Wahab MS, Sirajudeen KN, Salleh MS, Gurtu S

Int J Mol Sci, 2011;12(3):1888-907.
PMID: 21673929 DOI: 10.3390/ijms12031888

Oxidative stress is implicated in the pathogenesis and/or complications of hypertension and/or diabetes mellitus. A combination of these disorders increases the risk of developing cardiovascular events. This study investigated the effects of streptozotocin (60 mg/kg; ip)-induced diabetes on blood pressure, oxidative stress and effects of honey on these parameters in the kidneys of streptozotocin-induced diabetic Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). Diabetic WKY and SHR were randomized into four groups and received distilled water (0.5 mL) and honey (1.0 g/kg) orally once daily for three weeks. Control SHR had reduced malondialdehyde (MDA) and increased systolic blood pressure (SBP), catalase (CAT) activity, and total antioxidant status (TAS). SBP, activities of glutathione peroxidase (GPx) and glutathione reductase (GR) were elevated while TAS was reduced in diabetic WKY. In contrast, SBP, TAS, activities of GPx and GR were reduced in diabetic SHR. Antioxidant (honey) treatment further reduced SBP in diabetic SHR but not in diabetic WKY. It also increased TAS, GSH, reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio, activities of GPx and GR in diabetic SHR. These data suggest that differences in types, severity, and complications of diseases as well as strains may influence responses to blood pressure and oxidative stress.
Hypoglycemic and antioxidant effects of honey supplementation in streptozotocin-induced diabetic rats

Erejuwa OO, Omotayo EO, Gurtu S, Sulaiman SA, Ab Wahab MS, Sirajudeen KN, et al.

Int J Vitam Nutr Res, 2010 Jan;80(1):74-82.
PMID: 20533247 DOI: 10.1024/0300-9831/a000008

Oxidative stress plays a crucial role in the development of diabetic complications. The aims of this study were to investigate whether honey could reduce hyperglycemia and ameliorate oxidative stress in kidneys of streptozotocin-induced diabetic rats.
Single-nucleotide polymorphisms and mRNA expression of CYP1B1 influence treatment response in triple negative breast cancer patients undergoing chemotherapy

Abdul Aziz AA, Md Salleh MS, Mohamad I, Krishna Bhavaraju VM, Mazuwin Yahya M, Zakaria AD, et al.

J Genet, 2018 Dec;97(5):1185-1194.
PMID: 30555068

Triple negative breast cancer (TNBC) is typically associated with poor and interindividual variability in treatment response. Cytochrome P450 family 1 subfamily B1 (CYP1B1) is a metabolizing enzyme, involved in the biotransformation of xenobiotics and anticancer drugs. We hypothesized that, single-nucleotide polymorphisms (SNPs), CYP1B1 142 C>G, 4326 C>G and 4360 A>G, and CYP1B1 mRNA expression might be potential biomarkers for prediction of treatment response in TNBC patients. CYP1B1 SNPs genotyping (76 TNBC patients) was performed using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism methods and mRNA expression of CYP1B1 (41 formalin-fixed paraffin embeddedblocks) was quantified using quantitative reverse transcription PCR. Homozygous variant genotype (GG) and variant allele (G) of CYP1B1 4326C>G polymorphism showed significantly higher risk for development of resistance to chemotherapy with adjusted odds ratio (OR): 6.802 and 3.010, respectively. Whereas, CYP1B1 142 CG heterozygous genotype showed significant association with goodtreatment response with adjusted OR: 0.199. CYP1B1 142C-4326G haplotype was associated with higher risk for chemoresistance with OR: 2.579. Expression analysis revealed that the relative expression of CYP1B1 was downregulated (0.592) in cancerous tissue compared with normal adjacent tissues. When analysed for association with chemotherapy response, CYP1B1 expression was found to be significantly upregulated (3.256) in cancerous tissues of patients who did not respond as opposed to those of patients who showed response to chemotherapy. Our findings suggest that SNPs together with mRNA expression of CYP1B1 may be useful biomarkers to predict chemotherapy response in TNBC patients.
TRPM4 expression is associated with activated B cell subtype and poor survival in diffuse large B cell lymphoma

Loo SK, Ch'ng ES, Md Salleh MS, Banham AH, Pedersen LM, Møller MB, et al.

Histopathology, 2017 Jul;71(1):98-111.
PMID: 28248435 DOI: 10.1111/his.13204

AIMS: Transient receptor potential channel melastatin 4 (TRPM4) is an ion channel that regulates influx of calcium cations (Ca2+ ). Recent studies suggest that TRPM4 is an oncoprotein, and its up-regulated transcript level has been reported in diffuse large B cell lymphoma (DLBCL). We aimed to investigate TRPM4 protein expression pattern in non-malignant tissues and DLBCL cases, and its association with clinico-demographic parameters and survival in DLBCL.
METHODS AND RESULTS: Analysis of publicly available DLBCL microarray data sets showed that TRPM4 transcripts were up-regulated in DLBCL compared to normal germinal centre B (GCB) cells, were expressed more highly in the activated B cell-like DLBCL (ABC-DLBCL) subtype and higher TRPM4 transcripts conferred worse overall survival (OS) in R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone)-treated DLBCL cases (P < 0.05). Our immunohistochemical analysis showed that TRPM4 was expressed in various human tissues but not in normal B cells within lymphoid tissues (reactive tonsil, lymph node and appendix). TRPM4 protein was present in 26% (n = 49 of 189) of our cohort of R-CHOP-treated DLBCL cases and this was associated significantly with more aggressive clinical parameters, including higher lactate dehydrogenase (LDH), Eastern Cooperative Oncology Group (ECOG) scores or stage (P < 0.01 for each of the parameters) and the ABC-DLBCL subtype (P = 0.016). TRPM4 positivity conferred significantly worse OS (P = 0.004) and progression-free survival (PFS) (P = 0.005). Worse OS remained associated significantly with TRPM4 positivity in multivariate analysis, including higher International Prognostic Index (IPI) or the non-GCB DLBCL phenotype (P < 0.05).
CONCLUSIONS: TRPM4 protein expression is up-regulated in DLBCL cases compared to non-malignant B cells with preferential expression in ABC-DLBCL cases, and it confers significantly poorer DLBCL patient outcomes.
Fulltext Frequency, geographical distribution and outcomes of pit viper bites in Malaysia consulted to Remote Envenomation Consultancy Services (RECS) from 2017 to 2020

Qamruddin RM, Safferi RS, Mohamed Ismail Z, Salleh MS, Abd Hamid MNH, Frederic Ng VER, et al.

PLoS Negl Trop Dis, 2023 Aug;17(8):e0011569.
PMID: 37585486 DOI: 10.1371/journal.pntd.0011569

Not all pit viper species are present in every state of Malaysia and their distribution varies according to altitude. There is limited information on pit viper bite incidence and its geographical distribution. This was a cross-sectional study of confirmed pit viper bite cases referred to Remote Envenomation Consultancy Services (RECS) from January 2017 to December 2020. Data was collected following the approval of institutional research ethics committee. Universal sampling methods were used. Confirmed pit viper bite cases in each state, geographical location and the antivenom used were reported. A total of 523 confirmed pit viper bite injuries occurred over the 4-year study period. The majority were Malaysians, male and young adults. Most were non-occupational related (83.9%) and involved the upper limbs (46.8%). The commonest pit viper species involved was Trimeresurus purpureomaculatus (23.7%). Green pit viper antivenom (GPAV) was the most frequent antivenom used (n = 51) with the majority of patients requiring only one dose (3 vials). This study provides a better appreciation of indigenous pit viper species distribution for each state and reflects the requirement of appropriate antivenom to be stocked in each state or district hospital.

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