Displaying publications 21 - 40 of 89 in total

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  1. Fulltext Nuclear localization and intensity of staining of nm23 protein is useful marker for breast cancer progression
    Ismail NI, Kaur G, Hashim H, Hassan MS
    Cancer Cell Int, 2008;8:6.
    PMID: 18454879 DOI: 10.1186/1475-2867-8-6
    Breast cancer is the most common cause of cancer death in the western world. The expression differences of many proteins are associated with breast cancer progression or suppression. The purpose of the study was to determine the expression of nm23 protein in the invasion status and metastatic potential of breast cancer by using tissue microarray and to determine its role in breast cancer based on the expression of nm23 gene product.
  2. Fulltext S100A4 overexpression proves to be independent marker for breast cancer progression
    Ismail NI, Kaur G, Hashim H, Hassan MS
    Cancer Cell Int, 2008 Sep 05;8:12.
    PMID: 18771601 DOI: 10.1186/1475-2867-8-12
    BACKGROUND: Breast cancer is the most common cancer and cause of deaths in women around the world. Oncogene amplification usually occurs late in tumor progression and correlates well with aggressiveness of tumor. In fact the function of the S100A4 protein and its role in metastasis is unclear at present. The purpose of the study was to determine the expression of S100A4 protein in the invasion status and metastatic potential of breast cancer by using tissue microarray and to determine its role in breast cancer based on the expression of S100A4 gene product.

    METHODS: S100A4 protein expression was examined by immunohistochemistry (IHC) using commercially available tissue microarray containing malignant and normal breast tissue cores from 216 patients.

    RESULTS: S100A4 was absent in normal breast tissues while positive in 45.1% of infiltrating ductal carcinoma (IDC) node negative and 48.8% of infiltrating lobular carcinoma node negative. In paired samples, S100A4 protein was expressed in 13.5% of IDC node positive cases and 35.1% of matched lymph node metastasis.

    CONCLUSION: S100A4 protein expression appears widely expressed in early and advanced breast cancer stages compared with normal breast. Our study suggests S100A4 may play a role in breast cancer progression and may prove to be an independent marker of breast cancer which appears to be down regulated in more advanced stages of breast cancer.

  3. Fulltext Cancer Tissue Classification Using Supervised Machine Learning Applied to MALDI Mass Spectrometry Imaging
    Mittal P, Condina MR, Klingler-Hoffmann M, Kaur G, Oehler MK, Sieber OM, et al.
    Cancers (Basel), 2021 Oct 27;13(21).
    PMID: 34771551 DOI: 10.3390/cancers13215388
    Matrix assisted laser desorption/ionization mass spectrometry imaging (MALDI MSI) can determine the spatial distribution of analytes such as protein distributions in a tissue section according to their mass-to-charge ratio. Here, we explored the clinical potential of machine learning (ML) applied to MALDI MSI data for cancer diagnostic classification using tissue microarrays (TMAs) on 302 colorectal (CRC) and 257 endometrial cancer (EC)) patients. ML based on deep neural networks discriminated colorectal tumour from normal tissue with an overall accuracy of 98% in balanced cross-validation (98.2% sensitivity and 98.6% specificity). Moreover, our machine learning approach predicted the presence of lymph node metastasis (LNM) for primary tumours of EC with an accuracy of 80% (90% sensitivity and 69% specificity). Our results demonstrate the capability of MALDI MSI for complementing classic histopathological examination for cancer diagnostic applications.
  4. Use of tryptic peptide MALDI mass spectrometry imaging to identify the spatial proteomic landscape of colorectal cancer liver metastases
    Li CMY, Briggs MT, Lee YR, Tin T, Young C, Pierides J, et al.
    Clin Exp Med, 2024 Mar 16;24(1):53.
    PMID: 38492056 DOI: 10.1007/s10238-024-01311-5
    Colorectal cancer (CRC) is the second leading cause of cancer-related deaths worldwide. CRC liver metastases (CRLM) are often resistant to conventional treatments, with high rates of recurrence. Therefore, it is crucial to identify biomarkers for CRLM patients that predict cancer progression. This study utilised matrix-assisted laser desorption/ionisation mass spectrometry imaging (MALDI-MSI) in combination with liquid chromatography-tandem mass spectrometry (LC-MS/MS) to spatially map the CRLM tumour proteome. CRLM tissue microarrays (TMAs) of 84 patients were analysed using tryptic peptide MALDI-MSI to spatially monitor peptide abundances across CRLM tissues. Abundance of peptides was compared between tumour vs stroma, male vs female and across three groups of patients based on overall survival (0-3 years, 4-6 years, and 7+ years). Peptides were then characterised and matched using LC-MS/MS. A total of 471 potential peptides were identified by MALDI-MSI. Our results show that two unidentified m/z values (1589.876 and 1092.727) had significantly higher intensities in tumours compared to stroma. Ten m/z values were identified to have correlation with biological sex. Survival analysis identified three peptides (Histone H4, Haemoglobin subunit alpha, and Inosine-5'-monophosphate dehydrogenase 2) and two unidentified m/z values (1305.840 and 1661.060) that were significantly higher in patients with shorter survival (0-3 years relative to 4-6 years and 7+ years). This is the first study using MALDI-MSI, combined with LC-MS/MS, on a large cohort of CRLM patients to identify the spatial proteome in this malignancy. Further, we identify several protein candidates that may be suitable for drug targeting or for future prognostic biomarker development.
  5. 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.
  6. Fulltext Protein Profiling in Human Papillomavirus-Associated Cervical Carcinogenesis: Cornulin as a Biomarker for Disease Progression
    Kumarasamy G, Ismail MN, Tuan Sharif SE, Desire C, Mittal P, Hoffmann P, et al.
    Curr Issues Mol Biol, 2023 Apr 20;45(4):3603-3627.
    PMID: 37185759 DOI: 10.3390/cimb45040235
    Nearly 90% of cervical cancers are linked to human papillomavirus (HPV). Uncovering the protein signatures in each histological phase of cervical oncogenesis provides a path to biomarker discovery. The proteomes extracted from formalin-fixed paraffin-embedded tissues of the normal cervix, HPV16/18-associated squamous intraepithelial lesion (SIL), and squamous cell carcinoma (SCC) were compared using liquid chromatography-mass spectrometry (LC-MS). A total of 3597 proteins were identified, with 589, 550, and 1570 proteins unique to the normal cervix, SIL, and SCC groups, respectively, while 332 proteins overlapped between the three groups. In the transition from normal cervix to SIL, all 39 differentially expressed proteins were downregulated, while all 51 proteins discovered were upregulated in SIL to SCC. The binding process was the top molecular function, while chromatin silencing in the SIL vs. normal group, and nucleosome assembly in SCC vs. SIL groups was the top biological process. The PI3 kinase pathway appears crucial in initiating neoplastic transformation, while viral carcinogenesis and necroptosis are important for cell proliferation, migration, and metastasis in cervical cancer development. Annexin A2 and cornulin were selected for validation based on LC-MS results. The former was downregulated in the SIL vs. normal cervix and upregulated in the progression from SIL to SCC. In contrast, cornulin exhibited the highest expression in the normal cervix and lowest in SCC. Although other proteins, such as histones, collagen, and vimentin, were differentially expressed, their ubiquitous expression in most cells precluded further analysis. Immunohistochemical analysis of tissue microarrays found no significant difference in Annexin A2 expression between the groups. Conversely, cornulin exhibited the strongest expression in the normal cervix and lowest in SCC, supporting its role as a tumor suppressor and potential biomarker for disease progression.
  7. Myxoid liposarcoma of the breast in a 25-year-old female as a diagnostic pitfall in fine needle aspiration cytology: report of a rare case
    Pant I, Kaur G, Joshi SC, Khalid IA
    Diagn Cytopathol, 2008 Sep;36(9):674-7.
    PMID: 18677756 DOI: 10.1002/dc.20913
    Primary sarcomas of the breast are extremely rare comprising less than 1.0% of all malignant tumors of the breast. It is even rarer to be reported in a 25-year-old female. This can cause a diagnostic dilemma not only for the clinician but also for the cytopathologist. A 25-year-old woman presented with a well defined firm, mobile lump in her right breast. With fine needle aspiration cytology (FNAC) and ultrasonography a diagnosis of fibroadenoma was made. The patient underwent lumpectomy. Histopathologically it was diagnosed as myxoid liposarcoma. This case is reported to highlight the fact that, even though rare in young females but the possibility of a breast lump being a myxoid liposarcoma does exist. This report discusses a primary myxoid liposarcoma of female breast, considers cytologic differential diagnoses with review of the relevant literature.
  8. Clustering of cardiovascular risk factors in a middle-income country: a call for urgency
    Selvarajah S, Haniff J, Kaur G, Hiong TG, Cheong KC, Lim CM, et al.
    Eur J Prev Cardiol, 2013 Apr;20(2):368-75.
    PMID: 22345688 DOI: 10.1177/2047487312437327
    BACKGROUND: This study aimed to estimate the prevalence of cardiovascular risk factors and its clustering. The findings are to help shape the Malaysian future healthcare planning for cardiovascular disease prevention and management.
    METHODS: Data from a nationally representative cross-sectional survey was used. The survey was conducted via a face-to-face interview using a standardised questionnaire. A total of 37,906 eligible participants aged 18 years and older was identified, of whom 34,505 (91%) participated. Focus was on hypertension, hyperglycaemia (diabetes and impaired fasting glucose), hypercholesterolaemia and central obesity.
    RESULTS: Overall, 63% (95% confidence limits 62, 65%) of the participants had at least one cardiovascular risk factor, 33% (32, 35%) had two or more and 14% (12, 15%) had three risk factors or more. The prevalence of hypertension, hyperglycaemia, hypercholesterolaemia and central obesity were 38%, 15%, 24% and 37%, respectively. Women were more likely to have a higher number of cardiovascular risk factors for most age groups; adjusted odds ratios ranging from 1.1 (0.91, 1.32) to 1.26 (1.12, 1.43) for the presence of one risk factor and 1.07 (0.91, 1.32) to 2.00 (1.78, 2.25) for two or more risk factors.
    CONCLUSIONS: Cardiovascular risk-factor clustering provides a clear impression of the true burden of cardiovascular disease risk in the population. Women displayed higher prevalence and a younger age shift in clustering was seen. These findings signal the presence of a cardiovascular epidemic in an upcoming middle-income country and provide evidence that drastic measures have to be taken to safeguard the health of the nation.
    Study name: National Health and Morbidity Survey (NHMS-2006)
  9. IGFBP-2 in cervical cancer development
    Kaur G, Balasubramaniam SD, Lee YJ
    Exp Mol Pathol, 2020 04;113:104362.
    PMID: 31870856 DOI: 10.1016/j.yexmp.2019.104362
    OBJECTIVE: Increased expression of insulin-like growth factor binding protein 2, IGFBP-2, is associated with many cancers, though its role in cervical cancer is unclear. The aim of this study was to investigate the expression of IGFBP-2 protein and the transcriptomics profile of genes involved in the IGF signaling pathway during cervical cancer development.

    DESIGN: Immunohistochemical expression of IGFBP-2 protein was semi-quantitatively assessed in tissue microarrays containing 9 normal cervix, 10 low grade cervical intraepithelial neoplasia (LGCIN), 10 high grade cervical intraepithelial neoplasia (HGCIN) and 42 squamous cell carcinoma (SCC) cases. The gene expression profiles of IGFBP-2, IGF-1, IGF-1R, PTEN, MDM2, AKT1 and TP53 were determined in three cervical tissue samples each from normal cervix, human papillomavirus (HPV)-infected LGCIN, HGCIN and SCC, using Human Transcriptome Array 2.0.

    RESULTS: IGFBP-2 protein was highly expressed in the cytoplasm of SCC cells compared to normal cervix (p = .013). The expression was not significantly associated with CIN grade or SCC stage. Transcriptomics profiling demonstrated upregulation of IGFBP-2 and TP53 in HGCIN and SCC compared to normal cervix. IGF-1, IGF-1R and PTEN genes were downregulated in all histological groups. IGF-1 gene was significantly downregulated in SCC (p = .031), while PTEN gene was significantly downregulated in HGCIN (p = .012), compared to normal cervix. MDM2 and AKT1 genes were downregulated in LGCIN and HGCIN, while upregulated in SCC.

    CONCLUSION: In cervical carcinogenesis, IGFBP-2 appears to play an oncogenic role, probably through an IGF-independent mechanism.

  10. Nuclear and stromal expression of Manic fringe in renal cell carcinoma
    Cheng WK, Kaur G, Sjöberg E, Frödin M, Egevad L, Harmenberg U, et al.
    Exp Mol Pathol, 2021 Aug 08;122:104667.
    PMID: 34371013 DOI: 10.1016/j.yexmp.2021.104667
    Renal cell carcinoma (RCC) is the most common type of kidney cancer and has the highest mortality rate among genitourinary cancers. Despite the advances in molecular targeted therapies to treat RCC, the inevitable emergence of resistance has delineated the need to uncover biomarkers to prospectively identify patient response to treatment and more accurately predict patient prognosis. Fringe is a fucose specific β1, 3N-acetylglucosaminyltransferase that modifies the Notch receptors. Given the link between its function and aberrant Notch activation in RCC, Fringe may be implicated in this disease. The Fringe homologs comprise of Lunatic fringe (LFng), Manic fringe (MFng) and Radical fringe (RFng). MFng has been reported to play a role in cancer. MFng is also essential in the development of B cells. However, the expression profile and clinical significance of MFng, and its association with B cells in RCC are unknown. CD20 is a clinically employed biomarker for B cells. This pilot study aimed to determine if MFng protein expression can be utilized as a prospective biomarker for therapeutics and prognosis in RCC, as well as to determine its association with CD20+ B cells. Analysis of publicly available MFng gene expression datasets on The Cancer Genome Atlas Netlwork (TCGA) identified MFng gene expression to be up-regulated in Kidney Clear Cell Renal Carcinoma (KIRC) patients. However there was no significant association between the patient survival probability and the level of MFng expression in this cohort. Immunohistochemistry performed on a tissue microarray containing cores from 64 patients revealed an elevated MFng protein expression in the epithelial and stromal tissues of RCC compared to the normal kidney, suggesting a possible role in tumorigenesis. Our study describes for the first time to our knowledge, the protein expression of MFng in the nuclear compartment of normal kidney and RCC, implicating a prospective involvement in gene transcription. At the cellular level, cytoplasmic MFng was also abundant in the normal kidney and RCC. However, MFng protein expression in the malignant epithelial and stromal tissue of RCC had no positive correlation with the patients' overall survival, progression-free survival and time to metastasis, as well as the gender, age, tumor stage and RCC subtype, indicating that MFng may not be an appropriate prognostic marker. The association between CD20+ B cells and epithelial MFng was found to approach borderline insignificance. Nonetheless, these preliminary findings may provide valuable information on the suitability of MFng as a potential therapeutic molecular marker for RCC, thus warrants further investigation using a larger cohort.
  11. Fulltext In-House Packed Porous Graphitic Carbon Columns for Liquid Chromatography-Mass Spectrometry Analysis of N-Glycans
    Young C, Condina MR, Briggs MT, Moh ESX, Kaur G, Oehler MK, et al.
    Front Chem, 2021;9:653959.
    PMID: 34178940 DOI: 10.3389/fchem.2021.653959
    Protein glycosylation is a common post-translational modification that modulates biological processes such as the immune response and protein trafficking. Altered glycosylation profiles are associated with cancer and inflammatory diseases, as well as impacting the efficacy of therapeutic monoclonal antibodies. Consisting of oligosaccharides attached to asparagine residues, enzymatically released N-linked glycans are analytically challenging due to the diversity of isomeric structures that exist. A commonly used technique for quantitative N-glycan analysis is liquid chromatography-mass spectrometry (LC-MS), which performs glycan separation and characterization. Although many reversed and normal stationary phases have been utilized for the separation of N-glycans, porous graphitic carbon (PGC) chromatography has become desirable because of its higher resolving capability, but is difficult to implement in a robust and reproducible manner. Herein, we demonstrate the analytical properties of a 15 cm fused silica capillary (75 µm i.d., 360 µm o.d.) packed in-house with Hypercarb PGC (3 µm) coupled to an Agilent 6550 Q-TOF mass spectrometer for N-glycan analysis in positive ion mode. In repeatability and intermediate precision measurements conducted on released N-glycans from a glycoprotein standard mixture, the majority of N-glycans reported low coefficients of variation with respect to retention times (≤4.2%) and peak areas (≤14.4%). N-glycans released from complex samples were also examined by PGC LC-MS. A total of 120 N-glycan structural and compositional isomers were obtained from formalin-fixed paraffin-embedded ovarian cancer tissue sections. Finally, a comparison between early- and late-stage formalin-fixed paraffin-embedded ovarian cancer tissues revealed qualitative changes in the α2,3- and α2,6-sialic acid linkage of a fucosylated bi-antennary complex N-glycan. Although the α2,3-linkage was predominant in late-stage ovarian cancer, the alternate α2,6-linkage was more prevalent in early-stage ovarian cancer. This study establishes the utility of in-house packed PGC columns for the robust and reproducible LC-MS analysis of N-glycans.
  12. Fulltext Pilomatricoma as a diagnostic pitfall in clinical practice: report of two cases and review of literature
    Pant I, Joshi SC, Kaur G, Kumar G
    Indian J Dermatol, 2010 Oct;55(4):390-2.
    PMID: 21430899 DOI: 10.4103/0019-5154.74566
    Pilomatricoma (PMC) is a relatively uncommon benign skin neoplasm arising from the skin adnexa. Since the first description of PMC in 1880, there has been a gradual increase in understanding of the morphologic features and clinical presentation of this tumor. However, difficulties still persist in making clinical and cytologic diagnosis. We report the clinical and histopathological findings of two cases of pilomatricoma. In case 1, a 10-year-old girl presented with a right upper back mass. In case 2, a nine-year-old girl presented with a left ear lobe mass. The clinical findings in both the cases were suggestive of epidermoid/dermoid cyst. However, subsequent histopathologic examination confirmed these cases as pilomatricoma. This report reveals that pilomatricoma is a frequently misdiagnosed entity in clinical practice. The purpose of this article is to create awareness among clinicians on the possibility of pilomatricoma as a cause of solitary skin nodules, especially those on the head, neck or upper extremities.
  13. Fulltext Comparison of the Framingham Risk Score, SCORE and WHO/ISH cardiovascular risk prediction models in an Asian population
    Selvarajah S, Kaur G, Haniff J, Cheong KC, Hiong TG, van der Graaf Y, et al.
    Int J Cardiol, 2014 Sep;176(1):211-8.
    PMID: 25070380 DOI: 10.1016/j.ijcard.2014.07.066
    BACKGROUND:Cardiovascular risk-prediction models are used in clinical practice to identify and treat high-risk populations, and to communicate risk effectively. We assessed the validity and utility of four cardiovascular risk-prediction models in an Asian population of a middle-income country.
    METHODS:Data from a national population-based survey of 14,863 participants aged 40 to 65 years, with a follow-up duration of 73,277 person-years was used. The Framingham Risk Score (FRS), SCORE (Systematic COronary Risk Evaluation)-high and -low cardiovascular-risk regions and the World Health Organization/International Society of Hypertension (WHO/ISH) models were assessed. The outcome of interest was 5-year cardiovascular mortality. Discrimination was assessed for all models and calibration for the SCORE models.
    RESULTS:Cardiovascular risk factors were highly prevalent; smoking 20%, obesity 32%, hypertension 55%, diabetes mellitus 18% and hypercholesterolemia 34%. The FRS and SCORE models showed good agreement in risk stratification. The FRS, SCORE-high and -low models showed good discrimination for cardiovascular mortality, areas under the ROC curve (AUC) were 0.768, 0.774 and 0.775 respectively. The WHO/ISH model showed poor discrimination, AUC=0.613. Calibration of the SCORE-high model was graphically and statistically acceptable for men (χ(2) goodness-of-fit, p=0.097). The SCORE-low model was statistically acceptable for men (χ(2) goodness-of-fit, p=0.067). Both SCORE-models underestimated risk in women (p<0.001).
    CONCLUSIONS:The FRS and SCORE-high models, but not the WHO/ISH model can be used to identify high cardiovascular risk in the Malaysian population. The SCORE-high model predicts risk accurately in men but underestimated it in women.
    KEYWORDS:Cardiovascular disease prevention; Mortality; Risk prediction; Risk score; Validation
  14. Germline mutation and protein expression analysis of mismatch repair genes MSH6 and PMS2 in Malaysian Lynch syndrome patients
    Zahary MN, Kaur G, Hassan MR, Sidek AS, Singh H, Yeh LY, et al.
    Int J Colorectal Dis, 2014 Feb;29(2):261-2.
    PMID: 24072394 DOI: 10.1007/s00384-013-1770-1
  15. Andrographolide is neither a human organic anion transporter 1 (hOAT1) substrate nor inhibitor
    Chong YM, Kaur G, Tan ML
    J Asian Nat Prod Res, 2019 Aug;21(8):754-771.
    PMID: 30606060 DOI: 10.1080/10286020.2018.1520704
    Andrographolide, a major bioactive compound isolated from Andrographis paniculata (Burm. F.) Nees, was evaluated for its effects on the hOAT1 membrane transporter. Substrate determination and inhibition of hOAT1-mediated uptake transport assay was carried out using recombinant CHO-hOAT1 cells. The results showed that the uptake ratio of andrographolide was less than 2.0 at all concentrations tested, indicating that andrographolide is not a hOAT1 substrate. Andrographolide has no significant effects on the p-aminohippuric acid uptake and on the mRNA and protein expression of hOAT1. In conclusion, andrographolide may not pose a drug-herb interaction risk related to hOAT1.
  16. Fulltext Toxicological studies of Orthosiphon stamineus (Misai Kucing) standardized ethanol extract in combination with gemcitabine in athymic nude mice model
    Yehya AHS, Asif M, Kaur G, Hassan LEA, Al-Suede FSR, Abdul Majid AMS, et al.
    J Adv Res, 2019 Jan;15:59-68.
    PMID: 30581613 DOI: 10.1016/j.jare.2018.05.006
    Pancreatic cancer has the highest mortality rate among cancers due to its aggressive biology and lack of effective treatment. Gemcitabine, the first line anticancer drug has reduced efficacy due to acquired resistance. The current study evaluates the toxicological effects of Orthosiphon stamineus (O.s) and its marker compound (rosmarinic acid) in combination with gemcitabine. O.s (200 or 400 mg/kg/day) and rosmarinic acid (32 mg/kg/day) were administered orally and gemcitabine (10 mg/kg/3 days) intraperitoneally either alone or in combination treatment for fourteen days. Parameters including blood serum biochemistry, hematology, myeloid-erythroid ratio, incident of lethality, and histopathological analysis of liver, kidney, and spleen tissues were studied. Neither, individual drugs/extract nor chemo-herbal combinations at tested doses induced any toxicity and damage to organs in nude mice when compared to control group. Toxicological data obtained from this study will help to select the best doses of chemo-herbal combination for future pancreatic xenograft tumor studies.
  17. A preliminary evaluation of the efficacy and safety of Cogent db (an ayurvedic drug) in the glycemic control of patients with type 2-diabetes
    Shekhar KC, Achike FI, Kaur G, Kumar P, Hashim R
    J Altern Complement Med, 2002 Aug;8(4):445-57.
    PMID: 12230905
    A nonrandomized, non-placebo-controlled clinical trial to evaluate the efficacy of Cogent db (an herbal preparation; Cybele Herbal Laboratories [PVT] Ltd. Kochi, Kerala State, India) as an adjuvant in the treatment of patients with type 2 diabetes was carried out during a 3-month period.
  18. Fulltext Immunohistochemical expression of MAP1LC3A and MAP1LC3B protein in breast carcinoma tissues
    Othman EQ, Kaur G, Mutee AF, Muhammad TS, Tan ML
    J Clin Lab Anal, 2009;23(4):249-58.
    PMID: 19623642 DOI: 10.1002/jcla.20309
    Autophagy is a protein degradation process within the cell and its deregulation has been linked to various diseases and the formation of cancer. One of the important proteins involved in the autophagy process is microtubule-associated protein 1 light chain 3 (MAP1LC3). The aims of this study were to determine the MAP1LC3A and MAP1LC3B protein expression in both normal and cancer breast tissues and to determine the relationship between the expression of these proteins and type of tissues. Immunohistochemistry assessments were carried out on tissue microarrays consisting of breast tissues. MAP1LC3A expression was detected in 52/56 of normal breast tissue cores and 65/67 of breast cancer tissue cores. MAP1LC3B expression was detected in 55/56 of normal breast tissue cores and 67/67 of breast cancer tissue cores. MAP1LC3A and MAP1LC3B protein are expressed in the majority of normal and cancer breast tissues. A large number of MAP1LC3A and MAP1LC3B positive breast cancer tissues cores have high proportion of stained cells (81-100%) as compared with normal breast tissues. However, a significantly higher number of breast cancer tissues were found to express the MAP1LC3A protein with strong immunoreactivity as compared with the normal tissues, suggesting that MAP1LC3A may play a role in breast cancer development.
  19. Immunohistochemical determination of the P15 protein expression in cutaneous squamous cell carcinoma
    Moad AI, Lan TM, Kaur G, Hashim H, Mabruk MJ
    J Cutan Pathol, 2009 Feb;36(2):183-9.
    PMID: 18564286 DOI: 10.1111/j.1600-0560.2008.00989.x
    The tumor suppressor gene p15(INK4b) is a cyclin-dependent kinase inhibitor, in which its inactivation has been determined in primary tumors and in several tumor-derived cell lines. The precise role of p15(INK4b) protein expression in cutaneous squamous cell carcinoma (SCC) is currently not known. In a previous study, we have shown the frequent occurrence of allelic imbalance/loss of heterozygosity in cutaneous SCC using two microsatellite markers flanking the p15(INK4b) gene. This study is a continuation of our previous study and aims to determine the possible role of p15(INK4b) protein expression in the genesis of cutaneous SCC. P15(INK4b) protein expression was determined using immunohistochemical approach in 107 cases of cutaneous SCC tissue arrays and 19 cases of normal human skin tissues. The expression of p15(INK4b) was significantly reduced in the cutaneous SCC cases as compared with normal human skin (p = 0.017 and p < 0.05). However, there were no significant relationship between clinicopathologic variables of the patients (age, sex and tumor grade) and p15(INK4b) protein expression. The absence of p15(INK4b) expression in the majority of tissue microarray cores of cutaneous SCC indicated that p15(INK4b) could possibly be involved in the pathogenesis of cutaneous SCC.
  20. Characterization of renal hemodynamic and structural alterations in rat models of renal impairment: role of renal sympathoexcitation
    Salman IM, Ameer OZ, Sattar MA, Abdullah NA, Yam MF, Najim HS, et al.
    J Nephrol, 2010 5 4;24(1):68-77.
    PMID: 20437405 DOI: 10.5301/jn.2010.6
    BACKGROUND: Renal sympathetic innervation plays an important role in the control of renal hemodynamics and may therefore contribute to the pathophysiology of many disease states affecting the kidney. Thus, the present study aimed to investigate the role of the renal sympathetic nervous system in the early deteriorations of renal hemodynamics and structure in rats with pathophysiological states of renal impairment.

    METHODS: Anesthetized Sprague Dawley (SD) rats with cisplatin-induced acute renal failure (ARF) or streptozotocin (STZ)-induced diabetes mellitus (DM) were subjected to a renal hemodynamic study 7 days after cisplatin and STZ administration. During the acute study, renal nerves were electrically stimulated, and responses in renal blood flow (RBF) and renal vascular resistance (RVR) were recorded in the presence and absence of renal denervation. Post mortem kidney collection was performed for histopathological assessment.

    RESULTS: In innervated ARF or DM rats, renal nerve stimulation produced significantly lower (all p<0.05, vs. innervated control) renal vasoconstrictor responses. These responses were markedly abolished when renal denervation was performed (all p<0.05); however, they appeared significantly higher compared with denervated controls (all p<0.05). Kidney injury was suppressed in denervated ARF, while, irrespective of renal denervation, renal specimens from DM rats were comparable to controls.

    CONCLUSIONS: Renal sympathoexcitation is involved in the pathogenesis of the renal impairment accompanying ARF and DM, and may even precede the establishment of an observable renal injury. There is a possible enhancement in the renal sensitivity to intrarenal norepinephrine following renal denervation in ARF and DM rats.
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