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Strategies and challenges for systematically mapping biologically significant molecular pathways regulating carcinoma epithelial-mesenchymal transition

Said NA, Simpson KJ, Williams ED

Cells Tissues Organs (Print), 2013;197(6):424-34.
PMID: 23774256 DOI: 10.1159/000351717

Enormous progress has been made towards understanding the role of specific factors in the process of epithelial-mesenchymal transition (EMT); however, the complex underlying pathways and the transient nature of the transition continues to present significant challenges. Targeting tumour cell plasticity underpinning EMT is an attractive strategy to combat metastasis. Global gene expression profiling and high-content analyses are among the strategies employed to identify novel EMT regulators. In this review, we highlight several approaches to systematically interrogate key pathways involved in EMT, with particular emphasis on the features of multiparametric, high-content imaging screening strategies that lend themselves to the systematic discovery of highly significant modulators of tumour cell plasticity.

Matched MeSH terms: Neoplasms/pathology*
Total testosterone and sex hormone-binding globulin are significantly associated with metabolic syndrome in middle-aged and elderly men

Chin KY, Ima-Nirwana S, Mohamed IN, Aminuddin A, Ngah WZ

Exp. Clin. Endocrinol. Diabetes, 2013 Jul;121(7):407-12.
PMID: 23765753 DOI: 10.1055/s-0033-1345164

Testosterone and sex hormone-binding globulin (SHBG) have been shown to be associated with metabolic syndrome (MS) in men. This study aimed at validating these relationships in a group of middle-aged and elderly men and assessing their strength of association to MS. A cross-sectional study of 332 Malaysian men aged 40 years and above was conducted. The blood of subject was collected under fasting condition for determination of testosterone, SHBG, glucose and lipid levels. Their medical history, smoking and alcohol consumption status, waist circumference (WC), body mass index (BMI) and blood pressure (BP) were recorded. All testosterone and SHBG levels were significantly reduced in MS subjects compared to non-MS subjects (p<0.05). Testosterone and SHBG were correlated significantly with most of the MS indicators without adjustments. In multiple regression analysis, the triglyceride level was the only MS indicator that was significantly, inversely and independently associated with all testosterone measurements and SHBG (p<0.05). Waist circumference was significantly and negatively associated with SHBG level (p<0.05) though not independent of BMI. Total testosterone and SHBG were significantly and inversely associated with the presence of MS. Testosterone and SHBG are potential intervention targets for the prevention of MS in men.

Matched MeSH terms: Metabolic Syndrome X/pathology
Fulltext Oral cancer prognosis based on clinicopathologic and genomic markers using a hybrid of feature selection and machine learning methods

Chang SW, Abdul-Kareem S, Merican AF, Zain RB

BMC Bioinformatics, 2013;14:170.
PMID: 23725313 DOI: 10.1186/1471-2105-14-170

Machine learning techniques are becoming useful as an alternative approach to conventional medical diagnosis or prognosis as they are good for handling noisy and incomplete data, and significant results can be attained despite a small sample size. Traditionally, clinicians make prognostic decisions based on clinicopathologic markers. However, it is not easy for the most skilful clinician to come out with an accurate prognosis by using these markers alone. Thus, there is a need to use genomic markers to improve the accuracy of prognosis. The main aim of this research is to apply a hybrid of feature selection and machine learning methods in oral cancer prognosis based on the parameters of the correlation of clinicopathologic and genomic markers.

Matched MeSH terms: Mouth Neoplasms/pathology
Does long term supplementation of vitamin E cause detrimental effects on the central nervous system? Morphological and histological study in experimental male Wistar rats

Mohamad Fairuz Y, Azian A, Nursiati MT, Srijit D, Hamzaini AH, Wan Zurinah WN, et al.

Clin Ter, 2013;164(2):119-24.
PMID: 23698204 DOI: 10.7417/CT.2013.1529

Aging is attributed to neuronal loss associated with increased oxidative stress. Vitamin E, and in particular, tocotrienol are potent antioxidants, which have been shown to be neuroprotective. The main aim of the present study was to observe the effect of long term intake of vitamin E in the form of tocotrienol rich fraction (TRF) and refined, bleached, deodorized palm olein (RBDPO) on the brain of experimental rats.

Matched MeSH terms: Central Nervous System Diseases/pathology*
Fulltext Effect of germicidal UV-C light(254 nm) on eggs and adult of house dustmites, Dermatophagoides pteronyssinus and Dermatophagoides farinae (Astigmata: Pyroglyhidae)

Lah EF, Musa RN, Ho TM

Asian Pac J Trop Biomed, 2012 Sep;2(9):679-83.
PMID: 23569994 DOI: 10.1016/S2221-1691(12)60209-3

To examined the immediate and 24 hours post- irradiation germicidal effects of UV-C lamp on eggs and adults of house dust mites Dermatophagoides pteronyssinus (D. pteronyssinus) and Dermatophagoides farinae (D. farinae).

Matched MeSH terms: Ovum/pathology
Distinctive features of advancing breast cancer cells and interactions with surrounding stroma observed under the scanning electron microscope

Jaafar H, Sharif SE, Murtey MD

Asian Pac J Cancer Prev, 2012;13(4):1305-10.
PMID: 22799323

Breast cancer cells undergo transformation when they spread into surrounding tissues. Studies have shown that cancer cells undergo surface alterations and interact with the surrounding microenvironment during the invasion process. The aim of the present study was to analyse these cancer cell surface alterations and interactions of cancer cells and stroma. Twenty 1-methyl-1-nitrosourea-induced breast cancer samples taken from five rats were fixed in McDowell-Trump fixative and then washed in 0.1 M phosphate buffer. The samples were then treated with osmium tetroxide before being washed in distilled water and subsequently dehydrated through graded ethanols. The dehydrated samples were immersed in hexamethyldisilazane (HMDS), then following removal of excess HMDS, the samples were air dried at room temperature in a dessicator. The dried samples were mounted onto specimen stubs and coated with gold coater before being viewed under a scanning electron microscope. We detected the presence of membrane ruffles on the surface of cancer cells and the formation of unique surface membrane protrusions to enhance movement and adhesion to the surrounding stroma during the process of invasion. Advancing cancer cells demonstrated formation of lamellipodia and invadopodia. The stroma at the advancing edge was desmoplastic with many collagen fibres laid down near the cancer cells. Our data suggest that all of these abnormalities could act as hallmarks of invasiveness for breast cancer.

Matched MeSH terms: Breast Neoplasms/pathology*
The role of proton pump inhibitors in adenoid hypertrophy in children

Iqbal FR, Goh BS, Mazita A

Otolaryngol Head Neck Surg, 2012 Aug;147(2):329-34.
PMID: 22496101 DOI: 10.1177/0194599812444528

To establish the efficacy of proton pump inhibitors (PPI) in the treatment of adenoid hypertrophy in children.

Matched MeSH terms: Adenoids/pathology*
Fulltext Cellular transcripts of chicken brain tissues in response to H5N1 and Newcastle disease virus infection

Balasubramaniam VR, Wai TH, Omar AR, Othman I, Hassan SS

Virol J, 2012;9:53.
PMID: 22361110 DOI: 10.1186/1743-422X-9-53

Highly-pathogenic avian influenza (HPAI) H5N1 and Newcastle disease (ND) viruses are the two most important poultry viruses in the world, with the ability to cause classic central nervous system dysfunction in poultry and migratory birds. To elucidate the mechanisms of neurovirulence caused by these viruses, a preliminary study was design to analyze host's cellular responses during infections of these viruses.

Matched MeSH terms: Brain/pathology*
Fulltext Intramedullary cervical spine germinoma: a case report

Ashraf S

Med J Malaysia, 2012 Apr;67(2):207-9.
PMID: 22822645 MyJurnal

Primary intramedullary germinoma arising in the cervical spinal cord is a very rare entity. We present one such case arising in a young man who presented with radiculopathy and myelopathy, which was partially excised. Upon histological confirmation, he was treated successfully with radiotherapy alone. To our knowledge, this is only the second reported case worldwide which is histologically confirmed. Although extremely rare, differential diagnosis for intramedullary spinal cord tumor should include germinoma.

Matched MeSH terms: Cervical Vertebrae/pathology*
Fulltext Pancreatic metastases from ovarian carcinoma--diagnosis by endoscopic ultrasound-guided fine needle aspiration

Hadzri MH, Rosemi S

Med J Malaysia, 2012 Apr;67(2):210-1.
PMID: 22822646

Pancreatic metastases are very uncommon and originate most commonly from lung, colon, breast and kidney cancer. Ovarian adenocarcinoma has been reported as a primary site of pancreatic metastasis, but its diagnosis has rarely being reported by endoscopic ultrasound guided fine needle aspiration (EUS-FNA). We report a case of multiple metastases to the pancreas from ovarian carcinoma occurring four years after original resection of the primary tumour. Our patient presented with severe epigastric pain which was initially treated as acute pancreatitis. Further imaging modalities showed multiple large pseudocystic lesions in the pancreatic head and body. Subsequent EUS-FNA confirmed that the lesions were metastatic disease from an advanced ovarian carcinoma. She underwent palliative chemotherapy and the pancreatic lesion showed receding size.

Matched MeSH terms: Ovarian Neoplasms/pathology*
Quality of life in Malaysian colorectal cancer patients: a preliminary result

Natrah MS, Ezat S, Syed MA, Rizal AM, Saperi S

Asian Pac J Cancer Prev, 2012;13(3):957-62.
PMID: 22631679

OBJECTIVE: Rapidly increasing colorectal cancer (CRC) incidence in Malaysia and the introduction of cutting edge new treatments, which prolong survival, mean that treatment outcome measures meed to be evaluated, including consideration of patient's quality of life (QoL) assessment. There are limited data on QoL in CRC patients, especially in Malaysia. Therefore, this study was performed focusing on cancer stages and age groups.
METHODS: The cross sectional study was conducted from June to September 2011 at three public tertiary hospitals with the EORTC QLQ C-30 questionnaire in addition to face to face interview and review of medical records of 100 respondents.
RESULTS: The mean age was 57.3 (SD 11.9) years with 56.0% are males and 44.0% females, 62% of Malay ethnicity, 30% Chinese, 7% Indian and 1% Sikh. Majority were educated up to secondary level (42%) and 90% respondents had CRC stages III and IV. Mean global health status (GHS) score was 79.1 (SD 21.4). Mean scores for functional status (physical, emotional, role, cognitive, social) rangeds between 79.5 (SD 26.6) to 92.2 (SD 13.7). Mean symptom scores (fatigue, pain, nausea/vomiting, constipation, diarrhea, insomnia, dyspnoea, loss of appetite) ranged between 4.00 (SD 8.58) to 20.7 (SD 30.6). Respondents role function significantly deteriorates with increasing stage of the disease (p=0.044). Females had worse symptoms of pain (p=0.022), fatigue (p=0.031) and dyspnoea (p=0.031). Mean insomnia (p=0.006) and diarrhea (p=0.024) demonstrated significant differences between age groups.
CONCLUSION: QOL in CRC patients in this study was comparable to that in other studies done in developed countries. Pain, fatigue and dyspnoea are worse among female CRC patients. Given that functions deteriorates with advanced stage of the disease at diagnosis, a systematic screening programme to detect cases as early as possible is essential nationwide.

Matched MeSH terms: Colorectal Neoplasms/pathology
Fulltext Concurrent massive breast enlargement, myasthenia gravis and dermopathy as manifestations of penicillamine toxicity in a Wilson's disease patient

Tan SS, Latif SA, Poh WY

Med J Malaysia, 2012 Jun;67(3):323-5.
PMID: 23082426 MyJurnal

Penicillamine toxicity in Wilson's disease has been well reported but rarely seen now as newer agents are being used. We present a case who developed multiple rare complications of Penicillamine concurrently. Our patient is one of three siblings on Penicillamine, she was the only one who developed massive breast enlargement four months after commencing Penicillamine therapy, as well as dermatological adverse reactions and myasthenia gravis three more months later. All the adverse effects improved soon after substitution of the offending agent with Trientine.

Matched MeSH terms: Breast/pathology*
Evaluation of power Doppler ultrasonography for prostate biopsy in men with elevated serum prostate specific antigen levels

Ho CC, Khor TW, Singam P, Goh EH, Tan GH, Bahadzor B, et al.

Clin Ter, 2012;163(3):211-4.
PMID: 22964693

OBJECTIVE: To evaluate power doppler ultrasonography (PDU)-directed prostate biopsy in patients with elevated serum prostate specific antigen (PSA) levels.
MATERIALS AND METHODS: Men with serum total PSA levels of more than 4 ng/ml undergoing biopsy for the first time were included. Grey-scale transrectal ultrasound (TRUS) and PDU were performed. PDU signal on vascularity accumulation and perfusion characteristics were recorded and graded as normal or abnormal in the peripheral zone of the prostate. Abnormalities were defined on transverse image as radial or arc hypervascularities. A biopsy regime based on Vienna-normogram was performed in all patients.
RESULTS: Overall, prostate adenocarcinoma detection rate was 21.4% and abnormal accumulation on PDU signal was identified in 96.7% of those patients (p = 0.01). PDU directed prostate biopsies were positive in 66.7% of the patients with prostate cancer. The sensitivity, specificity, positive predictive value and negative predictive value of PDU signal alone for prostate cancer detection was 96.7%, 24.5% and 96.4% respectively, and PDU guided biopsies were 66.7%, 24.5%, 19.4% and 73% respectively.
CONCLUSIONS: The high sensitivity and negative predictive value of PDU makes it useful as an aid for TRUS biopsy in selected patient with previous negative biopsies at risk of harbouring prostate cancer.

Matched MeSH terms: Prostate/pathology*
Fulltext Cardiac mass in a patient with sigmoid adenocarcinoma: a metastasis?

Ngow HA, Khairina WM

Cardiovasc J Afr, 2012 Aug;23(7):e10-2.
PMID: 22915057 DOI: 10.5830/CVJA-2012-027

Cardiac metastasis from a bowel malignancy seldom occurs and there is a limited number of case reports published on this subject. Although colorectal cancer is the third commonest malignancy in Malaysia, the incidence of cardiac metastasis has never been reported. We report a case of an elderly man with recently diagnosed adenocarcinoma of the sigmoid colon, who presented with congestive cardiac failure secondary to mechanical obstruction by a right atrial mass. The intractable shock led to his sudden death before any intervention could be planned. If an intra-cavity cardiac mass is detected in a patient with an underlying metastatic malignancy, cardiac metastasis should be suspected. However, primary cardiac tumour or thrombus could also be the differential diagnosis. In our case, the definitive cardiac pathology remained unsolved as an autopsy was refused.

Matched MeSH terms: Sigmoid Neoplasms/pathology*
Pulmonary embolism following histoacryl glue embolization for a large thigh arteriovenous malformation

Harunarashid H, Lily S, Rozman Z, Azim MI, Das S

Clin Ter, 2012;163(5):393-5.
PMID: 23099967

Arteriovenous malformation (AVM) are commonly congenital in origin. We hereby describe the case of a 24-year-old male who was diagnosed of left thigh intramuscular AVM at the time of 14 years old. The computerized tomography (CT) scan confirmed a large deep seated intramuscular AVM with the size of 20 x 15 cm, with dilated and distended feeding vessel from profunda femoris artery (PFA) and superficial femoral artery (SFA). He also had another AVM near the left supracondylar region adherent to the sciatic nerve. The main AVM lesion was earlier treated with surgical resection and it remained for asymptomatic for next seven years. Following this, the patient presented again to the clinic with recurring swelling, pain and occasional paraesthesia on the same site. He was then managed with a series of embolization (total of 6 attempts) with histoacryl glue. These attempts of embolization were successful. The interesting case of pulmonary embolism due histoacryl glue following embolization of an AVM is described.

Matched MeSH terms: Arteriovenous Malformations/pathology
Fulltext Development of multicellular tumor spheroid (MCTS) culture from breast cancer cell and a high throughput screening method using the MTT assay

Ho WY, Yeap SK, Ho CL, Rahim RA, Alitheen NB

PLoS One, 2012;7(9):e44640.
PMID: 22970274 DOI: 10.1371/journal.pone.0044640

In comparison to monolayer cells, MCTS has been claimed as more suitable candidate for studying drug penetration due to the high resemblance to solid tumors. However, the cultivation of MCTS is cumbersome, time consuming, and most technique fail to generate spheroids with uniform sizes. Therefore, the application of spheroid cultures in high throughput screening has been rather limiting. Besides, the lack of a well established screening protocol method that is applicable to spheroid could also be attributed to this limitation. Here we report a simple way of cultivating homogenous MCTS cultures with compact and rigid structure from the MCF-7 cells. Besides, we had also made some modifications to the standard MTT assay to realize high throughput screening of these spheroids. Using the modified protocol, tamoxifen showed cytotoxicity effect towards MCTS cultures from MCF-7 with high consistency. The results correlated well with the cultures' response assessed by LDH release assay but the latter assay was not ideal for detecting a wide range of cytotoxicity due to high basal background reading. The MTT assay emerged as a better indicator to apoptosis event in comparison to the LDH release assay. Therefore, the method for spheroid generation and the modified MTT assay we reported here could be potentially applied to high throughput screening for response of spheroid cultures generated from MCF-7 as well as other cancer cell lines towards cytotoxic stimuli.

Matched MeSH terms: Breast Neoplasms/pathology*
Detection of cardiac geometry via difference intensity of echocardiogram images

Mohd Adib MA, Yusof MF, Ahmad Z, Mohd Hasni NH

J Integr Bioinform, 2012;9(2):195.
PMID: 22781711 DOI: 10.2390/biecoll-jib-2012-195

Echocardiogram is an ultrasound image of the heart that demonstrates the size, motion and composition of cardiac structures and is also used to diagnose various abnormalities of the heart including abnormal chamber size, shape and congenital heart disease. Echocardiography provides important morphological and functional details of the heart. Most of the presented automatic cardiac disease recognition systems that use echocardiograms based on defective anatomical region detection. In this paper we present a simple technique for cardiac geometry detection via echocardiogram images which conquer these borders and exploits cues from cardiac structure. To demonstrate the effectiveness of this technique, we present results for cardiac geometry detection through difference intensity of echocardiogram images. We have developed a simple program code for the prediction of cardiac geometry using difference intensity of echocardiogram images. With this code, users can generate node or point for detection of cardiac geometry as ventricle and atrium in size, shape and location.

Matched MeSH terms: Heart Diseases/pathology
Hemophagocytosis in dengue: comprehensive report of six cases

Tan LH, Lum LC, Omar SF, Kan FK

J Clin Virol, 2012 Sep;55(1):79-82.
PMID: 22789140 DOI: 10.1016/j.jcv.2012.06.005

Hemophagocytic syndrome is a potentially fatal disorder. It is being increasingly reported but remained under-recognized in dengue. Most reported cases were in association with plasma leakage and shock but multi-organ impairment was also observed. We describe the time-lines of 6 cases of confirmed dengue with varying severities of hemophagocytosis. All had persistent fever, cytopenia and elevated transaminases with markedly elevated ferritin levels during and beyond the plasma leakage phase. Acute renal failure and central nervous system manifestation were observed in two patients. Morphological hemophagocytosis was demonstrated in three patients. All survivors showed clinical and biochemical resolution of hemophagocytosis indicating its transient nature. Persistence of fever and cytopenia together with multi-organ dysfunction, out of proportion to and beyond the plasma leakage phase should prompt clinicians to consider this phenomenon.

Matched MeSH terms: Dengue/pathology*
Fulltext Effects of newcastle disease virus strains AF2240 and V4-UPM on cytolysis and apoptosis of leukemia cell lines

Alabsi AM, Bakar SA, Ali R, Omar AR, Bejo MH, Ideris A, et al.

Int J Mol Sci, 2011;12(12):8645-60.
PMID: 22272097 DOI: 10.3390/ijms12128645

Newcastle disease virus (NDV) is used as an antineoplastic agent in clinical tumor therapy. It has prompted much interest as an anticancer agent because it can replicate up to 10,000 times better in human cancer cells than in most normal cells. This study was carried out to determine the oncolytic potential of NDV strain AF2240 and V4-UPM on WEHI-3B leukemia cell line. Results from MTT cytotoxicity assay showed that the CD(50) values for both strains were 2 and 8 HAU for AF2240 and V4-UPM, respectively. In addition, bromodeoxyuridine (BrdU) and trypan blue dye exclusion assays showed inhibition in cell proliferation after different periods. Increase in the cellular level of caspase-3 and detection of DNA laddering using agarose gel electrophoresis on treated cells with NDV confirmed that the mode of cell death was apoptosis. In addition, flow-cytometry analysis of cellular DNA content showed that the virus caused an increase in the sub-G1 region (apoptosis peaks). In conclusion, NDV strains AF2240 and V4-UPM caused cytolytic effects against WEHI-3B leukemic cell line.

Matched MeSH terms: Blood Cells/pathology
Fulltext The inference of breast cancer metastasis through gene regulatory networks

Ahmad FK, Deris S, Othman NH

J Biomed Inform, 2012 Apr;45(2):350-62.
PMID: 22179053 DOI: 10.1016/j.jbi.2011.11.015

Understanding the mechanisms of gene regulation during breast cancer is one of the most difficult problems among oncologists because this regulation is likely comprised of complex genetic interactions. Given this complexity, a computational study using the Bayesian network technique has been employed to construct a gene regulatory network from microarray data. Although the Bayesian network has been notified as a prominent method to infer gene regulatory processes, learning the Bayesian network structure is NP hard and computationally intricate. Therefore, we propose a novel inference method based on low-order conditional independence that extends to the case of the Bayesian network to deal with a large number of genes and an insufficient sample size. This method has been evaluated and compared with full-order conditional independence and different prognostic indices on a publicly available breast cancer data set. Our results suggest that the low-order conditional independence method will be able to handle a large number of genes in a small sample size with the least mean square error. In addition, this proposed method performs significantly better than other methods, including the full-order conditional independence and the St. Gallen consensus criteria. The proposed method achieved an area under the ROC curve of 0.79203, whereas the full-order conditional independence and the St. Gallen consensus criteria obtained 0.76438 and 0.73810, respectively. Furthermore, our empirical evaluation using the low-order conditional independence method has demonstrated a promising relationship between six gene regulators and two regulated genes and will be further investigated as potential breast cancer metastasis prognostic markers.

Matched MeSH terms: Breast Neoplasms/pathology

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