Displaying publications 741 - 760 of 1065 in total

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  1. Huang D, Guo W, Gao J, Chen J, Olatunji JO
    Molecules, 2015;20(9):17405-28.
    PMID: 26393569 DOI: 10.3390/molecules200917405
    Clinacanthans nutans (Burm. f.) Lindau is a popular medicinal vegetable in Southern Asia, and its extracts have displayed significant anti-proliferative effects on cancer cells in vitro. However, the underlying mechanism for this effect has yet to be established. This study investigated the antitumor and immunomodulatory activity of C. nutans (Burm. f.) Lindau 30% ethanol extract (CN30) in vivo. CN30 was prepared and its main components were identified using high-performance liquid chromatography (HPLC) and mass spectrometry (LC/MS/MS). CN30 had a significant inhibitory effect on tumor volume and weight. Hematoxylin and eosin (H & E) staining and TUNEL assay revealed that hepatoma cells underwent significant apoptosis with CN30 treatment, while expression levels of proliferation markers PCNA and p-AKT were significantly decreased when treated with low or high doses of CN30 treatment. Western blot analysis of PAPR, caspase-3, BAX, and Bcl2 also showed that CN30 induced apoptosis in hepatoma cells. Furthermore, intracellular staining analysis showed that CN30 treatment increased the number of IFN-γ⁺ T cells and decreased the number of IL-4⁺ T cells. Serum IFN-γ and interleukin-2 levels also significantly improved. Our findings indicated that CN30 demonstrated antitumor properties by up-regulating the immune response, and warrants further evaluation as a potential therapeutic agent for the treatment and prevention of cancers.
    Matched MeSH terms: Carcinoma, Hepatocellular/drug therapy*; Carcinoma, Hepatocellular/immunology; Carcinoma, Hepatocellular/virology
  2. Fadlullah MZ, Chiang IK, Dionne KR, Yee PS, Gan CP, Sam KK, et al.
    Oncotarget, 2016 May 10;7(19):27802-18.
    PMID: 27050151 DOI: 10.18632/oncotarget.8533
    Emerging biological and translational insights from large sequencing efforts underscore the need for genetically-relevant cell lines to study the relationships between genomic alterations of tumors, and therapeutic dependencies. Here, we report a detailed characterization of a novel panel of clinically annotated oral squamous cell carcinoma (OSCC) cell lines, derived from patients with diverse ethnicity and risk habits. Molecular analysis by RNAseq and copy number alterations (CNA) identified that the cell lines harbour CNA that have been previously reported in OSCC, for example focal amplications in 3q, 7p, 8q, 11q, 20q and deletions in 3p, 5q, 8p, 18q. Similarly, our analysis identified the same cohort of frequently mutated genes previously reported in OSCC including TP53, CDKN2A, EPHA2, FAT1, NOTCH1, CASP8 and PIK3CA. Notably, we identified mutations (MLL4, USP9X, ARID2) in cell lines derived from betel quid users that may be associated with this specific risk factor. Gene expression profiles of the ORL lines also aligned with those reported for OSCC. By focusing on those gene expression signatures that are predictive of chemotherapeutic response, we observed that the ORL lines broadly clustered into three groups (cell cycle, xenobiotic metabolism, others). The ORL lines noted to be enriched in cell cycle genes responded preferentially to the CDK1 inhibitor RO3306, by MTT cell viability assay. Overall, our in-depth characterization of clinically annotated ORL lines provides new insight into the molecular alterations synonymous with OSCC, which can facilitate in the identification of biomarkers that can be used to guide diagnosis, prognosis, and treatment of OSCC.
    Matched MeSH terms: Carcinoma, Squamous Cell/drug therapy*; Carcinoma, Squamous Cell/genetics*; Carcinoma, Squamous Cell/pathology
  3. Patmanathan SN, Johnson SP, Lai SL, Panja Bernam S, Lopes V, Wei W, et al.
    Sci Rep, 2016 05 10;6:25650.
    PMID: 27160553 DOI: 10.1038/srep25650
    Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.
    Matched MeSH terms: Carcinoma, Squamous Cell
  4. Leow AH, Lim YY, Liew WC, Goh KL
    Aliment Pharmacol Ther, 2016 Apr;43(7):831-7.
    PMID: 26847417 DOI: 10.1111/apt.13550
    Marked epidemiological changes in upper gastrointestinal diseases and Helicobacter pylori infection have taken place in the Asian Pacific region. In particular, differences with respect to race in the multiracial Asian population in Malaysia have been important and interesting.
    Matched MeSH terms: Carcinoma, Squamous Cell/diagnosis; Carcinoma, Squamous Cell/ethnology; Carcinoma, Squamous Cell/microbiology
  5. Adwin Z, Nur A, Suhaimi S, Rahman R
    Oman Med J, 2016 Jan;31(1):69-72.
    PMID: 26816570 DOI: 10.5001/omj.2016.13
    Follicular thyroid adenoma and carcinoma are very common. Benign and malignant lesions are usually indistinguishable from cytology alone and often require confirmatory resection. The spread of follicular carcinoma is usually hematogenous and is treated with surgery and adjuvant radioactive iodine. Very rarely, metastases occur in the mediastinum. Patients usually present with severe compressive symptoms. With proper treatment and follow-up, the prognosis for these type of thyroid malignancies is excellent. In the case presented here, our patient presented to the Universiti Kebangsaan Malaysia Medical Center with a progressively enlarging anterior neck swelling. The swelling had started 10 years before his presentation. We diagnosed him with an advanced thyroid malignancy with bulky mediastinal metastases. After extensive investigations and counseling, we chose to treat the patient with tumor excision and mediastinal metastases resection. Typically, mediastinal resection involves the removal of the sternum and use of an acrylic implant to recreate the sternum. In this case, the sternum and ribs were removed with subsequent myocutaneous flap coverage for the wound defect. Our experience represents an alternative treatment option in cases where implant use is unsuitable.
    Matched MeSH terms: Carcinoma; Adenocarcinoma, Follicular
  6. Li LK, Rola AS, Kaid FA, Ali AM, Alabsi AM
    Arch Oral Biol, 2016 Apr;64:28-38.
    PMID: 26752226 DOI: 10.1016/j.archoralbio.2015.12.002
    Goniothalamin is a natural occurring styryl-lactone compound isolated from Goniothalamus macrophyllus. It had been demonstrated to process promising anticancer activity on various cancer cell lines. However, little study has been carried out on oral cancer. The aim of this study was to determine the cytotoxic effects of goniothalamin against H400 oral cancer cells and its underlying molecular pathways. Results from MTT assay demonstrated that goniothalamin exhibited selective cytotoxicity as well as inhibited cells growth of H400 in dose and time-dependent manner. This was achieved primarily via apoptosis where apoptotic bodies and membrane blebbing were observed using AO/PI and DAPI/Annexin V-FITC fluorescence double staining. In order to understand the apoptosis mechanisms induced by goniothalamin, apoptosis assessment based on mitochondrial membrane potential assay and cytochrome c enzyme-linked immunosorbent assay were carried out. Results demonstrated that the depolarization of mitochondrial transmembrane potential facilitated the release of mitochondrial cytochrome c into cytosol. Caspases assays revealed the activation of initiator caspase-9 and executioner caspase-3/7 in dose-dependent manners. This form of apoptosis was closely associated with the regulation on Bcl-2 family proteins, cell cycle arrest at S phase and inhibition of NF-κβ translocation from cytoplasm to nucleus. Conclusion, goniothalamin has the potential to act as an anticancer agent against human oral squamous cell carcinoma (H400 cells).
    Matched MeSH terms: Carcinoma, Squamous Cell
  7. Stepien M, Fedirko V, Duarte-Salles T, Ferrari P, Freisling H, Trepo E, et al.
    Cancer Epidemiol, 2016 Feb;40:179-87.
    PMID: 26773278 DOI: 10.1016/j.canep.2016.01.002
    INTRODUCTION: Serum liver biomarkers (gamma-glutamyl transferase, GGT; alanine aminotransferase, ALT; aspartate aminotransferase, AST; alkaline phosphatase, ALP; total bilirubin) are used as indicators of liver disease, but there is currently little data on their prospective association with risk of hepatobiliary cancers.

    METHODS: A nested-case control study was conducted within the prospective EPIC cohort (>520,000 participants, 10 European countries). After a mean 7.5 mean years of follow-up, 121 hepatocellular carcinoma (HCC), 34 intrahepatic bile duct (IHBC) and 131 gallbladder and biliary tract (GBTC) cases were identified and matched to 2 controls each. Circulating biomarkers were measured in serum taken at recruitment into the cohort, prior to cancer diagnosis. Multivariable adjusted conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (OR; 95%CI).

    RESULTS: In multivariable models, 1SD increase of each log-transformed biomarker was positively associated with HCC risk (OR(GGT)=4.23, 95%CI:2.72-6.59; OR(ALP)=3.43, 95%CI:2.31-5.10;OR(AST)=3.00, 95%CI:2.04-4.42; OR(ALT)=2.69, 95%CI:1.89-3.84; OR(Bilirubin)=2.25, 95%CI:1.58-3.20). Each liver enzyme (OR(GGT)=4.98; 95%CI:1.75-14.17; OR(AST)=3.10, 95%CI:1.04-9.30; OR(ALT)=2.86, 95%CI:1.26-6.48, OR(ALP)=2.31, 95%CI:1.10-4.86) but not bilirubin (OR(Bilirubin)=1.46,95%CI:0.85-2.51) showed a significant association with IHBC. Only ALP was significantly associated with GBTC risk (OR(ALP)=1.59, 95%CI:1.20-2.09).

    CONCLUSION: This study shows positive associations between circulating liver biomarkers in sera collected prior to cancer diagnoses and the risks of developing HCC or IHBC, but not GBTC.

    Matched MeSH terms: Carcinoma, Hepatocellular/metabolism; Carcinoma, Hepatocellular/epidemiology*; Carcinoma, Hepatocellular/pathology
  8. Johari B, Abdul Aziz YF, Krishnasamy S, Looi LM, Hashim SA, Raja Mokhtar RA
    Iran J Radiol, 2015 Apr;12(2):e11197.
    PMID: 26060549 DOI: 10.5812/iranjradiol.11197
    The presence of tumor thrombus in the right atrium is frequently the result of direct intraluminal extension of infra-diaphragmatic malignancy into the inferior vena cava (IVC) or supradiaphragmatic carcinoma into the superior vena cava (SVC). Right atrial tumor thrombus with extension into both SVC and IVC has not been reported in the literature. We present a patient who presented with symptoms of right atrial and SVC obstruction. Imaging revealed presence of a thrombus in the right atrium, extending to the SVC and IVC, with the additional findings of a left adrenal mass and multiple liver lesions. The histopathological examination of the right atrial mass revealed metastatic adenocarcinoma cells. The patient was given a presumptive diagnosis of metastatic adenocarcinoma, most likely adrenal in origin, with multiple hepatic lesions suspicious for metastasis. The clinical outcome of the patient was not favorable; the patient succumbed before the adrenal mass could be confirmed to be the primary tumor. This case highlights that in patients manifesting with extensive cavoatrial thrombus as, the existence of primary carcinoma should be considered especially in the adrenal cortex or in the lung.
    Matched MeSH terms: Adenocarcinoma; Carcinoma
  9. Ng BH, Rozita A, Adlinda A, Lee WC, Wan Zamaniah W
    Asian Pac J Cancer Prev, 2015;16(9):3827-33.
    PMID: 25987044
    BACKGROUND: Positive para-aortic lymph node (PALN) at diagnosis in cervical cancer patients confers an unfavorable prognosis. This study reviewed the outcomes of extended field radiotherapy (EFRT) and concurrent chemotherapy with extended field RT (CCEFRT) in patients with positive PALN at diagnosis.

    MATERIALS AND METHODS: Medical records of 407 cervical cancer patients between 1st January 2002 to 31st December 2012 were reviewed. Some 32 cases with positive PALN were identified to have received definitive extended field radiotherapy with or without chemotherapy. Treatment outcomes, clinicopathological factors affecting survival and radiotherapy related acute and late effects were analyzed.

    RESULTS: Totals of 13 and 19 patients underwent EFRT and CCEFRT respectively during the period of review. The median follow-up was 70 months. The 5-year overall survival (OS) was 40% for patients who underwent CCEFRT as compared to 18% for patients who had EFRT alone, with median survival sof 29 months and 13 months, respectively. The 5-years progression free survival (PFS) for patients who underwent CCEFRT was 32% and 18% for those who had EFRT. Median PFS were 18 months and 12 months, respectively. Overall treatment time (OTT) less than 8 weeks reduced risk of death by 81% (HR=0.19). Acute side effects were documented in 69.7% and 89.5% of patients who underwent EFRT and CCEFRT, respectively. Four patients (12.5%) developed radiotherapy late toxicity and there was no treatment-related death observed.

    CONCLUSIONS: CCEFRT is associated with higher 5-years OS and median OS compared to EFRT and with tolerable level of acute and late toxicities in selected patients with cervical cancer and PALN metastasis.

    Matched MeSH terms: Carcinoma, Squamous Cell/mortality; Carcinoma, Squamous Cell/secondary; Carcinoma, Squamous Cell/therapy*
  10. Wu YL, Zhou C, Liam CK, Wu G, Liu X, Zhong Z, et al.
    Ann Oncol, 2015 Sep;26(9):1883-1889.
    PMID: 26105600 DOI: 10.1093/annonc/mdv270
    BACKGROUND: The phase III, randomized, open-label ENSURE study (NCT01342965) evaluated first-line erlotinib versus gemcitabine/cisplatin (GP) in patients from China, Malaysia and the Philippines with epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC).

    PATIENTS AND METHODS: Patients ≥18 years old with histologically/cytologically confirmed stage IIIB/IV EGFR mutation-positive NSCLC and Eastern Cooperative Oncology Group performance status 0-2 were randomized 1:1 to receive erlotinib (oral; 150 mg once daily until progression/unacceptable toxicity) or GP [G 1250 mg/m(2) i.v. days 1 and 8 (3-weekly cycle); P 75 mg/m(2) i.v. day 1, (3-weekly cycle) for up to four cycles]. Primary end point: investigator-assessed progression-free survival (PFS). Other end points include objective response rate (ORR), overall survival (OS), and safety.

    RESULTS: A total of 217 patients were randomized: 110 to erlotinib and 107 to GP. Investigator-assessed median PFS was 11.0 months versus 5.5 months, erlotinib versus GP, respectively [hazard ratio (HR), 0.34, 95% confidence interval (CI) 0.22-0.51; log-rank P < 0.0001]. Independent Review Committee-assessed median PFS was consistent (HR, 0.42). Median OS was 26.3 versus 25.5 months, erlotinib versus GP, respectively (HR, 0.91, 95% CI 0.63-1.31; log-rank P = .607). ORR was 62.7% for erlotinib and 33.6% for GP. Treatment-related serious adverse events (AEs) occurred in 2.7% versus 10.6% of erlotinib and GP patients, respectively. The most common grade ≥3 AEs were rash (6.4%) with erlotinib, and neutropenia (25.0%), leukopenia (14.4%), and anemia (12.5%) with GP.

    CONCLUSION: These analyses demonstrate that first-line erlotinib provides a statistically significant improvement in PFS versus GP in Asian patients with EGFR mutation-positive NSCLC (NCT01342965).

    Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/drug therapy*; Carcinoma, Non-Small-Cell Lung/genetics; Carcinoma, Non-Small-Cell Lung/mortality
  11. Tan SH, Hindi KW, Chandran PA, Chong AW
    Iran J Otorhinolaryngol, 2015 May;27(80):243-6.
    PMID: 26082908
    INTRODUCTION: A rare case of basaloid squamous cell carcinoma (BSCC) of the larynx, which has not been previously reported, is described.

    CASE REPORT: A 60-year-old man was presented to the Otolaryngology Department with progressive dyspnoea and dysphagia to solids for over a period of 1 week. Direct laryngoscopy revealed a tumour at the laryngeal aspect of the epiglottis, which prolapsed into the laryngeal inlet each time the patient inspired. This resulted in an inspiratory stridor despite adequate glottic opening and normal mobility of the vocal cords.

    CONCLUSION: Therefore, in cases where a ball-valve lesion causes intermittent life-threatening airway obstruction, BSCC of the larynx, though rare, must be considered as a differential diagnosis.

    Matched MeSH terms: Carcinoma, Squamous Cell
  12. Zakaria N, Yusoff NM, Zakaria Z, Lim MN, Baharuddin PJ, Fakiruddin KS, et al.
    BMC Cancer, 2015;15:84.
    PMID: 25881239 DOI: 10.1186/s12885-015-1086-3
    Despite significant advances in staging and therapies, lung cancer remains a major cause of cancer-related lethality due to its high incidence and recurrence. Clearly, a novel approach is required to develop new therapies to treat this devastating disease. Recent evidence indicates that tumours contain a small population of cells known as cancer stem cells (CSCs) that are responsible for tumour maintenance, spreading and resistant to chemotherapy. The genetic composition of CSCs so far is not fully understood, but manipulation of the specific genes that maintain their integrity would be beneficial for developing strategies to combat cancer. Therefore, the goal of this study isto identify the transcriptomic composition and biological functions of CSCs from non-small cell lung cancer (NSCLC).
    Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/genetics*; Carcinoma, Non-Small-Cell Lung/metabolism; Carcinoma, Non-Small-Cell Lung/pathology
  13. Lopez JB, Balasegaram M, Timor J, Thambyrajah V
    Malays J Pathol, 1997 Jun;19(1):53-8.
    PMID: 10879242
    Although alpha-fetoprotein (AFP) is regarded as the reference marker for hepatocellular carcinoma (HCC), it sometimes produces false results. The objective of this study was to see if some of the readily available laboratory markers could complement AFP to improve the laboratory diagnosis of HCC. The markers tested and their sensitivities were: CA 125, 92%; ferritin, 71.3%; CA 19-9, 69.8%; beta-2-microglobulin (B2M), 53.3%; CA 72-4, 13.6%; and carcinoembryonic antigen (CEA), 10.6%. In comparison, AFP had a sensitivity of 58.8%. CA 72-4 and CEA (at the "tumour" cut-off level of 20 ng/ml) had specificities of 100%, and AFP, 97.4%. The specificities of the other markers were less impressive: CEA, 77.8% (at the cut-off level of 5 ng/ml); ferritin, 48.6%; CA 125, 48.5%; B2M, 39.6%; and CA 19-9, 37.3%. The efficiencies of the markers for HCC, which are based on the consideration of sensitivity and specificity together, were as follows: AFP, 77.6%; CA 125, 71.3%; ferritin, 60.5%; CA 19-9, 55.3; B2M, 46.9%; CEA, 40.8%; and CA 72-4, 34.5%. The receiver-operating characteristic plots confirmed AFP to be the most efficient marker for HCC. Nevertheless, it is proposed that CA 125 be combined with AFP for HCC screening because of their excellent sensitivity and specificity, respectively: a negative result for both, or even just CA 125 alone, would indicate that the disease is unlikely while a positive AFP (which would likely occur with a positive CA 125) would make its presence highly probable. A positive CA 125 and negative AFP would be equivocal for HCC. Other markers in combination with AFP are less useful.
    Matched MeSH terms: Carcinoma, Hepatocellular/blood*; Carcinoma, Hepatocellular/ethnology; Carcinoma, Hepatocellular/pathology
  14. Cheah PL
    Malays J Pathol, 1994 Jun;16(1):15-7.
    PMID: 16329570
    The surge of information on the aetiological association of the human papillomavirus (HPV) with some epithelial tumours emanating from various centres has prompted the initiation of a large-scale retrospective study at the Department of Pathology, University Hospital Kuala Lumpur to determine the prevalence and importance of this virus in some epithelial tumours of Malaysian patients. A retrospective analysis of 100 cases of large cell non-keratinising carcinoma of the uterine cervix by in-situ hybridisation on archival formalin-fixed, paraffin-embedded tissue has revealed the presence of HPV type 16 in 47% and type 18 in 41% of cases. This gives an overall detection rate of 88% of the two HPV types most commonly encountered in cervical carcinomas. Except for the unusually high frequency of HPV 18 detected in the cases, the overall prevalence is comparable to that reported in studies from most other centres. Although this higher frequency of HPV 18 may be due to geographical variation, the selection of the large cell non-keratinising type of squamous cell cervical carcinoma for study remains a possible reason for this phenomenon. In comparison to cervical carcinomas, HPV appears to be uncommon in penile carcinomas and HPV 6 was detected in only 1 of 23 cases studied.
    Matched MeSH terms: Carcinoma, Squamous Cell/epidemiology; Carcinoma, Squamous Cell/pathology; Carcinoma, Squamous Cell/virology*
  15. Shahrudin MD, Noori SM
    Hepatogastroenterology, 1997;44(14):441-4.
    PMID: 9164516
    BACKGROUND/AIMS: Recently an increasing number of young colorectal carcinoma patients attending the University Hospital, Kuala Lumpur were noted. This report represents our experience with patients suffering from colorectal cancer aged 30 years or younger.
    MATERIALS AND METHODS: All cases of primary carcinoma of the colon and rectum admitted to the University Hospital during 1990 to 1994 were respectively reviewed. Inclusion criteria was that the patient had been 30 years or younger. Data collected included age, gender, race, site of tumour, presenting symptomatology, duration of symptoms, histology, extension of tumour and nodal involvement predisposing factors, treatment and follow-up.
    RESULTS: 21 patients were included, 5 patients (24%) were 30 years old at diagnosis, 12 (57%) patients were aged 20-29 years and 4 patients (19%) were less than 20 years old. Thirteen of the 21 patients were female, and 8 (38%) were male, 6 of the 21 patients (29%) were Malaysian, while 1 was Indian (4%). The remainder were Chinese, 14 patients (67%). Six patients (29%) had their primary tumour located in the rectosigmoid, 4 (19%) in the left colon, 1 (4%) in the splenic flexure, 2 in the transverse colon (9%), 1 in the hepatic flexure (4%) and 5 in the caecum 24(%). One patient had a tumour too diffuse to detect a primary site at the time of operation. One patient with a family history of polyps had his entire colon removed at age 14. He had 3 separate foci of tumour. The 5-year survival rate was 25%.
    DISCUSSION: Most patients with extensive disease and mucinous histology. Lesions are commonly seen beyond the transverse colon (57%). Presentation included most commonly abdominal pain, haematochezia or haemoccult positive stools.
    CONCLUSION: The symptoms above should alert surgeons to colorectal carcinoma as a differential diagnosis
    Matched MeSH terms: Carcinoma/epidemiology*; Carcinoma/pathology; Carcinoma/secondary; Adenocarcinoma, Mucinous/epidemiology; Adenocarcinoma, Mucinous/pathology; Adenocarcinoma, Mucinous/secondary
  16. Lam KL, Yang KL, Sunderasan E, Ong MT
    Cell Prolif, 2012 Dec;45(6):577-85.
    PMID: 23046445 DOI: 10.1111/j.1365-2184.2012.00841.x
    OBJECTIVES: Latex from Hevea brasiliensis (natural rubber tree primarily cultivated for its rubber particles) has no known primary metabolic function, although its biological role is as a plant defence system. The present study has evaluated specific anti-proliferative effects of latex whole C-serum and its subfractions, on human cancer cell lines.

    MATERIALS AND METHODS: Cell viability assay using MTT, DNA fragmentation assay and real-time PCR were used to evaluate the cytotoxic effects of latex whole C-serum and its subfractions on the cell lines.

    RESULTS: MTT assay revealed very low LC(50) values, 2.0 and 280 ng/ml, for DCS and DCP treatments, respectively. DCS was proven to be more potent compared to DCP, in conferring specific anti-proliferative effects on the cancer cell lines. The study also indicated that anti-proliferative activity of pre-heated C-serum fractions diminished significantly.

    CONCLUSION: Although noteworthy cell death was reported, DNA fragmentation assay and real-time PCR confirmed that that induced by latex C-serum subfractions was not promoted via the classical apoptotic signalling pathway.

    Matched MeSH terms: Carcinoma, Hepatocellular/drug therapy*; Carcinoma, Hepatocellular/genetics; Carcinoma, Hepatocellular/metabolism
  17. Yip WK, Leong VC, Abdullah MA, Yusoff S, Seow HF
    Oncol Rep, 2008 Feb;19(2):319-28.
    PMID: 18202777
    The Akt pathway is one of the most common molecular alterations in various human malignancies. However, its involvement in nasopharyngeal carcinoma (NPC) tumorigenesis has not been well established. In this study, the status of Akt activation and expression of its upstream and downstream molecules was investigated in 64 NPC and 38 non-malignant nasopharyngeal tissues by immunohistochemistry. The hotspot mutations of PIK3CA, encoding the p110alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K), were also determined in 25 of these NPC tissues. No hotspot mutations were found in any of the samples tested. Akt was activated in 27 (42.2%) and 23 (35.9%) NPCs, as indicated by p-Akt (Thr308) and p-Akt (Ser473) immunoreactivity, respectively. PTEN loss did not correlate statistically with activated Akt. However, a positive correlation was observed between activated Akt and phospho-epidermal growth factor receptor (p-EGFR), suggesting that the EGFR signaling might be one of the upstream regulators of the Akt pathway. The phosphorylation of forkhead (FKHR) and Bcl-2 associated death domain (BAD), but not mammalian target of rapamycin and glycogen synthase kinase-3beta, was significantly correlated with Akt activation. This implies that Akt promotes cell proliferation (as estimated by Ki-67) and survival, at least, through the inactivation of FKHR and BAD in NPC. Our data revealed that the EGFR/PI3K/Akt signaling pathway is important in NPC pathogenesis and that PIK3CA hotspot mutations are rare in NPC.
    Matched MeSH terms: Carcinoma/enzymology*; Carcinoma/genetics; Carcinoma/pathology
  18. Lim KP, Hamid S, Lau SH, Teo SH, Cheong SC
    Oncol Rep, 2007 Jun;17(6):1321-6.
    PMID: 17487385 DOI: 10.3892/or.17.6.1321
    Inactivation of the retinoblastoma (pRB) pathway is a common event in oral squamous cell carcinoma particularly through the aberrant expression of the components within this pathway. This study examines the alterations of molecules within the pRB pathway by looking at the presence of homozygous deletions in p16(INK4A) and the expression patterns of pRB, cyclin D1 and CDK4, as well as the presence of human papillomavirus (HPV) in our samples. In our study, 5/20 samples demonstrated deletions of p16(INK4A) exon 1alpha. pRB overexpression was found in 20/20 samples, the expression was mainly observed in all layers of the epithelia, particularly in the basal layer where cells are actively dividing and aberrant pRB expression was found in 12/20 samples. Cyclin D1 and CDK4 overexpression was detected in 6/20 and 2/20 samples respectively in comparison to hyperplasias where both proteins were either not expressed or expressed at minimal levels (<10%). Strikingly, HPV was found to be present in all of our samples, suggesting that HPV plays a significant role in driving oral carcinogenesis. Notably, 17/20 of our samples showed more than one alteration in the pRB pathway, however, we did not find any significant relationship between the presence of HPV, homozygous deletion of p16(INK4A) and overexpression of pRB, cyclin D1 and CDK4. Collectively, this data demonstrates that alterations in the pRB pathway are a common event and involve the aberration of more than one molecule within the pathway. Furthermore, the involvement of HPV in all our samples suggests that HPV infection may play an important role in oral carcinogenesis.
    Matched MeSH terms: Carcinoma, Squamous Cell/etiology*; Carcinoma, Squamous Cell/metabolism; Carcinoma, Squamous Cell/virology
  19. Satar NA, Fakiruddin KS, Lim MN, Mok PL, Zakaria N, Fakharuzi NA, et al.
    Oncol Rep, 2018 Aug;40(2):669-681.
    PMID: 29845263 DOI: 10.3892/or.2018.6461
    Through the specific identification and direct targeting of cancer stem cells (CSCs), it is believed that a better treatment efficacy of cancer may be achieved. Hence, the present study aimed to identify a CSC subpopulation from adenocarcinoma cells (A549) as a model of non‑small cell lung cancer (NSCLC). Ιnitially, we sorted two subpopulations known as the triple‑positive (EpCAM+/CD166+/CD44+) and triple‑negative (EpCAM-/CD166-/CD44-) subpopulation using fluorescence-activated cell sorting (FACS). Sorted cells were subsequently evaluated for proliferation and chemotherapy-resistance using a viability assay and were further characterized for their clonal heterogeneity, self-renewal characteristics, cellular migration, alkaline dehydrogenase (ALDH) activity and the expression of stemness-related genes. According to our findings the triple‑positive subpopulation revealed significantly higher (P<0.01) proliferation activity, exhibited better clonogenicity, was mostly comprised of holoclones and had markedly bigger (P<0.001) spheroid formation indicating a better self-renewal capacity. A relatively higher resistance to both 5‑fluouracil and cisplatin with 80% expression of ALDH was observed in the triple‑positive subpopulation, compared to only 67% detected in the triple‑negative subpopulation indicated that high ALDH activity contributed to greater chemotherapy-resistance characteristics. Higher percentage of migrated cells was observed in the triple‑positive subpopulation with 56% cellular migration being detected, compared to only 19% in the triple‑negative subpopulation on day 2. This was similarly observed on day 3 in the triple‑positive subpopulation with 36% higher cellular migration compared to the triple‑negative subpopulation. Consistently, elevated levels of the stem cell genes such as REX1 and SSEA4 were also found in the triple‑positive subpopulation indicating that the subpopulation displayed a strong characteristic of pluripotency. In conclusion, our study revealed that the triple‑positive subpopulation demonstrated similar characteristics to CSCs compared to the triple‑negative subpopulation. It also confirmed the feasibility of using the triple‑positive (EpCAM+/CD166+/CD44+) marker as a novel candidate marker that may lead to the development of novel therapies targeting CSCs of NSCLC.
    Matched MeSH terms: Carcinoma, Non-Small-Cell Lung/drug therapy; Carcinoma, Non-Small-Cell Lung/genetics*; Carcinoma, Non-Small-Cell Lung/pathology
  20. Ahmad MS, Suardi N, Shukri A, Nik Ab Razak NNA, Oglat AA, Makhamrah O, et al.
    Eur J Radiol Open, 2020;7:100257.
    PMID: 32944594 DOI: 10.1016/j.ejro.2020.100257
    Introduction: Hepatocellular carcinoma (HCC) is one of the most common cancer in the world, and the effectiveness of its treatment lies in its detection in its early stages. The aim of this study is to mimic HCC dynamically through a liver phantom and apply it in multimodality medical imaging techniques including magnetic resonance imaging (MRI), computed tomography (CT), and ultrasound.

    Methods and materials: The phantom is fabricated with two main parts, liver parenchyma and HCC inserts. The liver parenchyma was fabricated by adding 2.5 wt% of agarose powder combined with 2.6 wt% of wax powder while the basic material for the HCC samples was made from polyurethane solution combined with 5 wt% glycerol. Three HCC samples were inserted into the parenchyma by using three cylinders implanted inside the liver parenchyma. An automatic injector is attached to the input side of the cylinders and a suction device connected to the output side of the cylinders. After the phantom was prepared, the contrast materials were injected into the phantom and imaged using MRI, CT, and ultrasound.

    Results: Both HCC samples and liver parenchyma were clearly distinguished using the three imaging modalities: MRI, CT, and ultrasound. Doppler ultrasound was also applied through the HCC samples and the flow pattern was observed through the samples.

    Conclusion: A multimodal dynamic liver phantom, with HCC tumor models have been fabricated. This phantom helps to improve and develop different methods for detecting HCC in its early stages.

    Matched MeSH terms: Carcinoma, Hepatocellular
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