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Fulltext C-kit proto-oncogene expression in uterine leiomyosarcomas: case series

Naik, V.R., Hasnan, J.

International Medical Journal Malaysia, 2008;7(2):51-54.
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Introduction: The proto-oncogene c-kit is the cellular homologue of the oncogene v-kit of HZ4 feline sarcoma virus. It is located on chromosome 4 (4q11-12) in the human genome. Interaction between the c-kit receptor and its ligand, stem cell factor, is essential in the development of tissues. C-kit expression has been identified in a number of different neoplasms like seminoma/dysgerminoma, and gastrointestinal stromal tumors (GIST). Recently it has been reported that c-kit is also present in leiomyosarcomas. Tyrosine kinase inhibitors (TKIs) are a promising new therapy in the treatment of cancer. These agents target cellular proteins like kit and its related homologues decreasing cellular proliferation and survival. TKIs may be helpful in treating leiomyosarcomas expressing c-kit. Materials and Methods: In this study a total of 6 cases diagnosed as leiomyosarcomas at Department of Pathology, Universiti Sains Malaysia, Kubang Kerian, Malaysia, were investigated for reactivity for c-kit using immunohistochemical stain. Stain was considered positive if more than 10 percent of the cells showed membrane or cytoplasmic positivity. Results: Two leiomyosarcomas stained faintly with c-kit and in less than 10 percent of the cells. The other 4 cases showed no staining. The control showed good membrane and cytoplasmic positivity. Conclusion: Uterine leiomyosarcomas did not express c-kit. The reason for this could be that the tumors are inherently c-kit negative. More study using larger number of cases is required to validate these findings and further molecular characterization of these mesenchymal tumors is needed to identify the true nature of these sarcomas.
Nucleolar organizer regions distribution in fine needle aspiration cytological smears from breast lesions

Hasnan J, Jayaram G

Malays J Pathol, 1996 Jun;18(1):35-41.
PMID: 10879223

Fine needle aspiration (FNA) cytology is now an integral part of the pre-operative investigation of breast lesions and the therapeutic protocol is today often planned on the basis of cytodiagnosis. However, from time to time the cytological picture may be equivocal or inconclusive. In recent years, nucleolar organizer region (NOR) scores have been explored for potential value in the diagnosis of malignancy as the scores in malignant nuclei are seen to be higher than in benign or reactive nuclei. With a view to applying NOR scoring in the evaluation of cytologically equivocal cases, we adopted the argyrophil technique for staining NOR s (AgNOR) in FNA cytological smears of 56 breast lesions, comprising 31 benign and 25 malignant lesions. Histological correlation was possible in 26 of these cases (17 malignant and 9 benign) and AgNOR scoring was done on paraffin sections of these as well. There was a significant difference between mean AgNOR scores in benign and malignant lesions in the cytological smears (P < 0.001). The AgNOR scores ranged from 2.5 to 5.0 per cell in benign lesions and 5.8 to 17.2 per cell in malignant lesions. None of the cases fell into the gray zone of overlap. One malignant lesion that was cytologically equivocal showed a mean AgNOR score of 6.08. The AgNOR scores on histological sections also showed a statistically significant difference (P < 0.001) between benign and malignant lesions with mean scores ranging from 1.34 to 2.58 dots per cell in benign lesions and scores of 2.42 to 5.28 dots per cell in malignant lesions. However, the scores overlapped in four cases and therefore it was considered unsuitable for routine diagnostic work. From this preliminary study, we conclude that an FNA AgNOR score of 5.0 and less strongly favours a benign lesion whereas a score above 5.0 would be in favour of a malignant lesion. A larger study would be needed to verify our impression that AgNOR scoring can be useful in cytologically equivocal cases.
Solvent abuse: a case report and a review

Sarvesvaran R, Hasnan J

Malays J Pathol, 1994 Dec;16(2):167-71.
PMID: 9053568

The deliberate inhalation of solvents among children and adolescents "for kicks" is becoming more common in the West. It was generally regarded as a relatively harmless practice and consequently little attention had been paid to the isolation of the toxic agent from the variety of substances used. It is now well recognised that solvent abuse not only can result in sudden death but also cause pathological changes to the liver, kidney, brain, heart and lungs. A case of toluene associated death in Malaysia is discussed both from a medico-legal and pathological standpoint.
Effects of asiatic acid on passive and active avoidance task in male Spraque-Dawley rats

Nasir MN, Habsah M, Zamzuri I, Rammes G, Hasnan J, Abdullah J

J Ethnopharmacol, 2011 Mar 24;134(2):203-9.
PMID: 21167268 DOI: 10.1016/j.jep.2010.12.010

Centella asiatica has a reputation to restore declining cognitive function in traditional medicine. To date, only a few compounds that show enhancing learning and memory properties are available. Therefore, the present study investigates the effects of for acute administration of asiatic acid (A-A) isolated from Centella asiatica administration on memory and learning in male Spraque-Dawley rats.
Fulltext Prevalence of colorectal cancer associated with Streptococcus bovis among inflammatory bowel and chronic gastrointestinal tract disease patients

Al-Jashamy K, Murad A, Zeehaida M, Rohaini M, Hasnan J

Asian Pac J Cancer Prev, 2010;11(6):1765-8.
PMID: 21338230

Colorectal cancer (CRC) is the second most common cause of cancer mortality among men and women worldwide; the risk of its occurrence has been shown to be increased by chronic bacterial infections. A case control study was therefore carried out at Hospital Universiti Sains Malaysia (HUSM) to determine the incidence of colorectal cancer associated with S. bovis infection. A total of 166 stool specimens were collected from diseased patients and healthy individuals and S. bovis isolates were identified. Suspected colon tumor and cancer cases were diagnosed and confirmed. It was found that overall prevalence of S. bovis was 41 (24.7%) out of 166 cases studied. Some 41(48.6%) of these S. bovis isolates was found in patients with colonic polyps, adenocarcinomas, inflammatory bowel disease (IBD) and chronic gastrointestinal tract (GIT). It was also found that colorectal cancer incidence was 24.7%, adenocarinomas accounting for 51% with the highest incidence in the sigmoid part of the colon. Among the IBD and chronic GIT cases, ulcerative colitis featured in the majority of cases (41.4%). In conclusion, there is a high incidence of colorectal cancer associated with S. bovis.
Acute toxicity study of the standardized methanolic extract of Mitragyna speciosa Korth in rodent

Harizal SN, Mansor SM, Hasnan J, Tharakan JK, Abdullah J

J Ethnopharmacol, 2010 Sep 15;131(2):404-9.
PMID: 20643198 DOI: 10.1016/j.jep.2010.07.013

ETHNOPHARMACOLOGICAL RELEVANCE: Mitragyna speciosa Korth (ketum) is widely used in Malaysia as a medicinal agent for treating diarrhea, worm infestations and also acts as an analgesic and antipyretic.
AIM: The aim of the study is to determine the acute toxicity of Mitragyna speciosa Korth standardized methanol extract in vivo in 4-weeks-old Sprague-Dawley rats.
METHODOLOGY: Rats were orally administrated single dose of 100, 500 and 1000 mg/kg Mitragyna speciosa Korth standardized methanol extract and the control group received 430 mg/kg of morphine orally. There were 10 rats in each group. All animals were sacrificed after 14 days of treatment. Eight parameters were tested: cage side observation, body weight measurement, food and water consumption, blood pressure, absolute and relative organ weight, hematology, biochemical analysis and histopathology, to look for evidence of toxicity.
RESULT: No mortality was noted after 14 days of treatment. In general, behavior, food and water consumption, hematological studies and organ weights showed no significant changes. The standardized methanol extraction of Mitragyna speciosa Korth increased rat blood pressure (systolic: 147.4+/-1.01, 131.64+/-4.94 and 137.8+/-4.46) after an hour of 100, 500 and 1000 mg/kg doses, respectively. Biochemical studies showed significant elevation of ALT, AST, albumin, triglycerides, cholesterol and albumin (p>0.05), at all levels of doses. But, nephrotoxicity evidenced by elevated creatinine was seen only at a dose of 1000 mg/kg. Histological examination showed congestion of sinusoids, hemorrhage hepatocytes, fatty change, centrilobular necrosis and increased number of Kuppfer cells in the liver of all Mitragyna speciosa Korth standardized methanol extract treated groups.
CONCLUSION: Oral administration of standardized methanolic extraction of Mitragyna speciosa Korth resulted in increasing rat blood pressure after an hour of drug administration. The highest dose of extract also induced acute severe hepatotoxicity and mild nephrotoxicity. However, Mitragyna speciosa Korth shows no effects on body weight, food and water consumption, absolute and relative organ weight and also hematology parameters.
Histopathological studies of cardiac lesions after long term administration of methamphetamine in high dosage--Part II

Islam MN, Jesmine K, Kong Sn Molh A, Hasnan J

Leg Med (Tokyo), 2009 Apr;11 Suppl 1:S147-50.
PMID: 19345131 DOI: 10.1016/j.legalmed.2009.02.035

A small amount of Methamphetamine (MA) can produce behavioural changes such as euphoria, increased alertness, paranoia, decreased appetite and increased physical activity. In cardiovascular system, it can produce chest pain and hypertension which can result in cardiovascular collapse. In addition, MA causes accelerated heartbeat, elevated blood pressure. It can also cause irreversible damage to blood vessels in the brain. A number of sympathomimetic amines are capable of causing myocardial damage, but the cardio-toxic action of MA has been of particular interest since standardized dosage consistently produces myocardial lesions. As this drug is a choice of many teenagers and young adults, the damage to their health, as well as their future aspects could be greatly affected, therefore more evidence must be sought to convince them the negative root and show them the optimism of recovery and salvation. To clarify the effect of Methamphetamine (MA) on myocardium, 56 male Wister rats aged four weeks were divided equally into MA, Methamphetamine withdrawal (MW), Placebo (P) and Control (C) group were examined following daily intra-peritoneal administration of MA at a dose of 5 mg/kg body weight for 2, 4, 8 and 12 weeks. Normal saline was similarly injected in P group. Light microscopic changes was seen in the myocardium of MA treated group including eosinophilic degeneration, atrophy, hypertrophy, disarray, edema, cellular infiltration, myolysis, granulation tissue, fibrosis and vacuolization. On the other hand, the withdrawal group showed evidence of gradual recovery of those myocardial changes. Optimism is therefore generated about possibility of returning towards normal by withdrawing of this drug by the addicts.
Orbital rhabdomyosarcoma in an HIV positive child

Khairy-Shamel ST, Shatriah I, Adil H, Zunaina E, Bakiah S, Rohaizan Y, et al.

Orbit, 2008;27(5):388-90.
PMID: 18836940 DOI: 10.1080/01676830802336629

We reported a case of orbital rhabdomyosarcoma with an intracranial extension in an HIV-infected child. It was an uncommon sarcoma in a retroviral-positive patient that resulted in a diagnostic and therapeutic dilemma. The child is currently asymptomatic following surgery, chemotherapy, and reinstitution of highly active retroviral therapy (HAART).
Immunoglobulin Heavy Chain Gene Rearrangement in Non B-cell Haematological Malignancies

Noor Haslina MN, Marini R, Rosnah B, Shafini MY, Wan Haslindawani WM, Mohd Nazri H, et al.

West Indian Med J, 2013 Nov;62(8):701-4.
PMID: 25014854 DOI: 10.7727/wimj.2013.253

OBJECTIVE: Clonality detection through amplifying immunoglobulin heavy chain (IGH) gene rearrangements by polymerase chain reaction (PCR) is a useful tool in diagnosis of various B-lymphoid malignancies. Immunoglobulin heavy chain gene rearrangement can be an optimal target for clonality detection in B-lymphoid malignancies. In the present study, we evaluated the presence of IGH gene rearrangement in non B-cell haemato-oncology patients including T-cell acute lymphoblastic leukaemia (T-ALL), acute myeloblastic leukaemia (AML) and biphenotypic leukaemia.
MEHTODS: We studied 18 cases of haematological malignancies which comprised five patients with T-ALL, 12 patients with AML and one with biphenotypic leukaemia.
RESULTS: We found that the incidence of IGH gene rearrangement in T-ALL and AML were three (60%) and two (16.7%), respectively. The patient with biphenotypic leukaemia was negative for IGH gene rearrangement.
CONCLUSION: Immunoglobulin gene rearrangement, which occurs in almost all haematological malignancies of B-cell lineage, also presents in a very small proportion of T-cell or myeloid malignancies.
Giant nerve sheath tumour: report of six cases

Ghani AR, Ariff AR, Romzi AR, Sayuthi S, Hasnan J, Kaur G, et al.

Clin Neurol Neurosurg, 2005 Jun;107(4):318-24.
PMID: 15885392

Giant nerve sheath tumour is a rare tumour originating from the nerve sheath. It differs from the conventional nerve sheath tumour only by the size these tumours can reach. There are two main type of tumours that occur in the nerve sheath which include neurofibroma and schwannoma. The current views are that schwannomas arise from the progenitor of the schwann cell. Whereas the neurofibroma series probably arise from a mesenchymal origin closer to a fibroblast. We report on six cases of nerve sheath tumour that occur in the spinal and paraspinal region that presented to us over a 5 year period.
Fulltext Relationship between apoptotic markers (Bax and Bcl-2) and biochemical markers in type 2 diabetes mellitus

Hasnan J, Yusof MI, Damitri TD, Faridah AR, Adenan AS, Norbaini TH

Singapore Med J, 2010 Jan;51(1):50-5.
PMID: 20200776

Bax is essential for apoptosis in normal cells. However, overexpression of Bcl-2 enhances cell survival by suppressing apoptosis in cells subjected to apoptosis-inducing stimuli. The aim of this study was to examine the expression of apoptotic (Bax and Bcl-2) and biochemical markers in type 2 diabetics mellitus.
Fulltext Expression of survivin and its clinicopathological correlations in invasive ductal carcinoma of the breast

Al-Joudi FS, Iskandar ZA, Hasnan J, Rusli J, Kamal Y, Imran AK, et al.

Singapore Med J, 2007 Jul;48(7):607-14.
PMID: 17609820

INTRODUCTION: Survivin is a 16.5-kDa intracellular protein that inhibits apoptosis and regulates cell division, and belongs to the inhibitors of apoptosis gene family. It appears to have an important role in regulating apoptosis at the cell cycle checkpoints. Survivin has been found to have a differential distribution in cancer compared to normal tissue, as it is over-expressed in malignant tumours.
METHODS: In addition to the demographical analysis of the disease, data from 382 women with invasive ductal carcinoma of the breast were collected from three hospitals in Northeast Malaysia, and analysed for survivin expression by immunohistochemistry.
RESULTS: Invasive ductal carcinoma of the breast was found to be the most prevalent breast cancer type. Survivin was detected in 260 (68.1 percent) study cases. In addition, significant correlations have been shown between survivin expression on one hand, and tumour size and lymph node involvement on the other hand (p-value is less than 0.05). However, no significant correlations were found with other clinicopathological factors, such as tumour histological grade, tumour side, oestrogen and progesterone receptors. Nuclear expression of survivin was detected in 16.5 percent of the study cases, cytoplasmic expression was detected in 24.1 percent, and 27.5 percent of the cases expressed survivin in both nuclear and cytoplasmic locations simultaneously. The subcellular localisation of survivin was significantly correlated (p is less than 0.001) with the lymph node involvement indicating its value in predicting the aggressiveness of tumour cells, since it increases the resistance to apoptosis and promotes cell proliferation.
CONCLUSION: This is the fi rst known report on survivin expression in cancer in West Malaysia and Southeast Asia. It emphasises the importance of the detection of survivin in breast cancer to aid in diagnosis, confirm malignancy, and to assess the disease progress and response to therapy.
Chromosomal alterations in Malaysian patients with nasopharyngeal carcinoma analyzed by comparative genomic hybridization

Natasya Naili MN, Hasnita CH, Shamim AK, Hasnan J, Fauziah MI, Narazah MY, et al.

Cancer Genet. Cytogenet., 2010 Dec;203(2):309-12.
PMID: 21156250 DOI: 10.1016/j.cancergencyto.2010.07.136

Nasopharyngeal carcinoma (NPC) is one of the most common cancers in Malaysia, mainly occurring among the Chinese population. To detect common genetic alterations in NPC, we screened seven cases of NPC using the comparative genomic hybridization (CGH) technique. Before proceeding to the CGH technique, the tumors were first confirmed to consist of 75% tumor cells or more. In brief, the technique consists of binding tumor DNA with normal DNA and human Cot-1 DNA, which is then hybridized to normal metaphase spreads. The slides were then counterstained with 4,6 diamino-2-phenylindole (DAPI II) for detection. Analyses were performed using CGH software (Cytovision). We found genetic alterations in all seven NPC samples. The common chromosomal gains (57%, four cases) were found on chromosome arms 1q, 4p, 5, 7q, 11, 14p, 15q, 18p, and 21p, and common chromosomal losses (43%, three cases) were found on chromosome arm 16p. Our results showed chromosomal alterations in all seven NPC cases in the Malaysian population. This result provides the platform for further investigations to locate tumor suppressor genes and oncogenes at specific chromosomal regions in Malaysian NPC patients.
Prognostic factors and survival rate of osteosarcoma: A single-institution study

Faisham WI, Mat Saad AZ, Alsaigh LN, Nor Azman MZ, Kamarul Imran M, Biswal BM, et al.

Asia Pac J Clin Oncol, 2017 Apr;13(2):e104-e110.
PMID: 25870979 DOI: 10.1111/ajco.12346

AIM: Osteosarcoma is a highly malignant primary bone tumor. The study aim to evaluate the prognostic factors influencing the survival rate in our center.
METHODS: This was a retrospective cohort study of all patients treated between January 2005 and December 2010.
RESULTS: We included 163 patients with an age range of 6-59 years (median = 19). The median follow-up was 47 months (range 36-84). The overall survival in patients who completed chemotherapy and surgery (n = 117) was 72% at 2 years and 44% at 5 years. Histologically, 99 (85%) had osteoblastic, 6 (5%) had chondroblastic and 3 (2.5%) had telangiectatic osteosarcoma. Limb salvage surgery was performed in 80 (49%) and 41 (25%) underwent amputation. However, 46 patients (28%) underwent no surgical intervention and incomplete chemotherapy. In total, 38/79 patients had a good chemotherapy response. There was a significantly better survival rate for limb salvage versus amputation. Independent prognostic factors for survival are compliance to treatment and presence of lung metastasis.
CONCLUSION: The overall survival of osteosarcoma patients was influenced by the presence of pulmonary metastases and compliance to treatment. Histological subtype, different chemotherapy regimens and histological necrosis after chemotherapy did not significantly influence survival. The patients who did not complete treatment had significantly poorer survival.

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