Introduction: Hepatocellular carcinoma is one of the most common cancers that affected human in more than half of the world population. Although there is yet any alternatives treatment found for this disease, the antitumor property of thymoquinone has been well studied in most of cancer cell lines. Nonetheless, poor bioavailability of TQ limits its efficiency. The encapsulation form of TQ, TQ-NLC is suggested to enhance its bioavailability as well as cytotoxicity towards cancer cells via increasing resistance time and targeting drug to specified location in the body. Therefore, it is a great advantage to look at the effects of TQ-NLC towards HepG2. This study is design to look at the anti-proliferative effect of TQ-NLC on HepG2 and the changes in the cells morphology. Methods: Both cells were bought from ATCC and cultured in supplemented DMEM. Cell viability was determined via MTT assay. Pro-apoptotic effect of TQ-NLC was further confirmed with Annexin V staining. Morphology hallmarks of apoptosis of treated cells were also analysed using inverted microscope. Images were captured at 24, 48 and 72 hours. Results: TQ-NLC was very potent towards HepG2 compared to 3T3 with the relative IC50 of 25 µM. TQ-NLC was also more potent compared to the non-encapsulated form, TQ. Further analysis confirmed that TQ-NLC capable to increase the percentage of apoptotic cells in time-dependent manner. Qualitatively, all treated cells displayed the apoptosis morphology with increasing concentration and longer time-point. Conclusion: TQ-NLC showed greater cytotoxic effects towards HepG2 which was further confirmed with the morphological analysis
Cancer

Bacteria and their metabolites are shown to be a potential therapeutic agent for cancer treatment. Much attention has been directed to Lactic acid bacteria (LAB) which exhibits several killing mechanisms via invasion and colonization of solid tumors. Discovery of the characteristics of postbiotic metabolites that exert the same probiotic effects has attracted immense attention towards anti-cancer effect. It is known that LAB improves health and composition of microbiota in the gut. Supplementation of LAB is proven to enhance the host immunity and modulation of the immune system to fight diseases including cancers. Lactobacillus plantarum I-UL4 is the LAB species isolated from Malaysian fermented food, Tapai Ubi which capable of producing bioactive metabolic products. In this review, the properties of UL4-PPM will be discussed including anti-microbial, anti-cancer and immunomodulatory effects. Overall, it would be beneficial to discover the potential effects of UL4-PPM to possibly serve as an alternative treatment for cancer.
Cancer

Introduction: Insulin-like growth factor binding protein-related protein 1 (IGFBP-rP1) is an important component of the IGF system that regulates insulin resistance-related to tumour development. The aim of this study is to investigate the expression of IGFBP-rP1 among female cancer patients who are known or not known to have Type 2 Diabetes Mellitus (T2DM). Materials and Methods: Using a cross-sectional design, cases of ovarian and breast cancer with clinical status of T2DM were selected over a 10-year period in Hospital Universiti Sains Malaysia. Immunohistochemical staining for IGFBP-rP1 was performed on paraffin-embedded tissues and the results were correlated with the patient’s demographic and clinicopathological data. Results: A total of 152 breast cancer patients were recruited into the current study with 33.5% (51/152) patients were positive T2DM. Most of the breast cancer patients with T2DM were IGFBP-rP1-negative (66.7%, 34/51). The IGFBP-rP1 expression was significantly difference between breast cancer subjects with and without T2DM (p<0.001). There was no significant association of IGFBP-rP1 expression with data on the demographic and clinicopathological profiles of patients with breast cancer. Meanwhile, positive IGFBP-rP1 expression was evident in 44 out of 108 (40.74%) ovarian cancer cases. Among these cases, 36 were T2DM. In contrast to breast cancer cases, IGFBP-rP1 was mostly expressed among ovarian cancer patients with T2DM (66.7%, 24/36, p < 0.001). However, the -positive expression was not significantly associated with any sociodemographic and clinicopathological features of ovarian cancers. Conclusions: Majority of breast cancer patients with T2DM did not express IGFBP-rP1. In contrast, majority of the ovarian cancer patients with T2DM expressed IGFBP-rP1.
Breast cancer ; ovarian cancer

No abstract available.
Cancer Vaccines*

Introduction: This study focused on PF4 effects on caspase-3,-6, -7, -8 and -9 which regulate the apopotosis process in breast cancer. Materials and Methods: Breast tumours were induced in forty 21-day-old female Sprague Dawley rats (SDRs) using MNU until tumour size reached 14.5 mm (SD: 0.5 mm). The rats were then divided into two groups: Group 1 (control injected with 0.9% saline; n = 20), and Group 2 (platelet factor 4 (PF4); n = 20). PF4 was administered through focal intralesional injection at 20 µg/lesion dose. Following 5-day treatment, the SDRs were sacrificed. Subsequently, representative sections from the tumour were obtained for haematoxylin and eosin (H&E) staining. The expressions of caspase-3, -6, -7, -8 and -9 were evaluated using immunohistochemistry (IHC) staining. Results: The majority of breast tumour specimens were of aggressive types [ncontrol = 13 (65%); nPF4 = 12 (60%)]. Invasive ductal carcinoma not otherwise specified (IDC-NOS) was the most commonly observed breast tumour histology for control and PF4 groups (n = 8 (40%) in respective groups). PF4-treated group exhibited significant differences in the caspase-3, -6 and -8 expression levels compared to the control group (all p < 0.001). There were no significant differences in caspase-7 (p = 0.347) and caspase-9 (p = 0.373) expression levels between both groups. Conclusion: This study found that PF4 acts via the caspase-mediated extrinsic apoptosis pathway without the involvement of the intrinsic pathway.
breast cancer

Introduction: Evaluation of HER2 status in breast cancer using immunohistochemistry (IHC) and in-situ-hybridisation (ISH) study is important to establish prognosis and to select patient for targeted therapy. Objective: The study aims to determine the concordance between HER2 protein IHC score and its gene status by dual-colour dual-hapten in-situ-hybridization (DDISH) study. Materials and Methods: Retrospective study was performed on 767 referred breast cancer cases over a period of five years. The HER2 IHC score (the initial and repeat test score) and the results of HER2 gene status by DDISH were retrieved from the histopathological reports. The agreement between initial IHC score with repeat test score was measured using Cohen Kappa. Chi square test analyzed the association between HER2 IHC score with its gene status by DDISH. Results: The concordance of HER2 IHC score between the initial and repeat test were 52.7% and 89.4% for IHC score 2+ and 3+ respectively. There was moderate agreement of HER2 IHC score between the initial and repeat test score (κ = 0.526, p<0.001). A significant association noted between HER2 IHC score with its gene status by DDISH (p<0.001). Only 56 out of 207 cases (27.1%) with 2+ IHC score showed HER2 gene amplification while the majority of cases with 3+ IHC score were gene-amplified (446 out of 451, 98.9%). Conclusion: ISH study should be done in all IHC-equivocal cases (2+) to select patient for targeted therapy. Gene amplification must also be confirmed in IHC-positive cases (3+) to prevent from giving non-effective treatment with possible adverse effects to patient with nonamplified HER2 gene.
breast cancer

Introduction: Liver cancer is among the main leading cause of mortality in Malaysia and the world. Therefore, there is an urgent need to understand the complex mechanisms and pathways involved in liver cancer. Methods: Microarray datasets GSE84402, GSE60502, GSE29721 and GSE19665 were downloaded from GEO database. The datasets were normalised and differentially expressed genes (DEGs) were calculated using GeneSpring software. GO and KEGG pathway enrichment analyses were then performed using DAVID. Finally, Cytoscape stringApp plugin was utilised to construct a protein-protein interaction (PPI) network. Results: A total of 1382, 714, 1038 and 1828 DEGs satisfying p value cut-off 0.01 and fold change cut-off 2.0 are identified from each dataset. 412 DEGs appeared in at least three datasets, consisting of 167 up-regulated and 245 down-regulated genes. These genes are most significantly enriched in terms related to cell division and mitotic nuclear division. Construction of PPI network produced a network with 275 nodes and 2157 edges with confidence score 0.7. Topological analysis identified CDK1, TOP2A and NDC80 as key genes. MCODE plugin extracted five modules from the network with mitotic cell cycle process being the most enriched term in module 1. Meanwhile, platelet degranulation, epoxygenase P450 pathway, cellular response to zinc ion and complement and coagulation cascade are the terms enriched in module 2, 3, 4 and 5. Conclusion: The key genes and pathways identified from this study provide information on the molecular mechanism underlying liver cancer to increase our understanding regarding liver cancer development and progression at molecular level
Liver cancer

Introduction: Curcumin is an active constituent derived from turmeric with a variety of pharmacological activities. It suppressed cell proliferation and induced apoptosis in several cancer cell lines. However, due to its poor bioavailability, derivative analogue of curcumin has been synthesized to enhance the drug-like effects. BHMC was synthesized by removing β-diketone moiety from curcumin structure and modify it into conjugated double bonds. It has been proved to exhibit stronger anticancer effects with improved bioavailability compared to curcumin. Objective: This study aims to investigate the toxicity effect of BHMC and curcumin on human liver cancer, HepG2 and non-cancer mouse fibroblast, 3T3. Methods: Both cell lines were purchased from ATCC and cultured in supplemented DMEM. Cell viability was determined via MTT assay and confirmed with trypan blue assay. Morphology hallmarks of apoptosis of both treated cells were analyzed using inverted microscope at 40X magnifications. Results: BHMC and curcumin were very potent towards HepG2 and normal 3T3. These data were further confirmed with trypan blue assay which showed that both compounds significantly reduced the percentage of HepG2 and 3T3 cells viability. Both treated cells also displayed all the morphology hallmarks of apoptosis upon treatment. Conclusion: BHMC has a greater cytotoxicity effect on HepG2 compared to curcumin despite its non-selective cytotoxicity effect on non-cancer 3T3.
Liver cancer

Cancer metastasis is a multistep process, which results in cancer cells disseminating to other organs. The crucial metastasis step involves cancer invasion which occurs via actin-protrusion by invasive malignant cells, termed as invadopodia. In solid tumours, invadopodia formation increases as a result of hypoxia which is found to be resistant against chemotherapy and radiotherapy. Phytochemicals have been potentially identified as a prime source of effective conventional drugs for metastasis treatments, which target cancer cell invasion, particularly molecular components of the invadopodia formation. The Hypoxia-Inducible Factor-1α (HIF-1α) is an essential target in terms of treatment for hypoxic tumour, as well as helping to identify the mode of action for the drugs, particularly phytochemical compounds. The aim of this review is to highlight the current development with regards to the ability of phytochemicals in targeting cancer metastasis, as well as phytochemical compounds which are able to inhibit HIF-1α and invadopodia formation. The use of phytochemicals for targeting hypoxic cancer cells may open new prospects for reducing cancer metastasis
Cancer Metastasis

INTRODUCTION: Ovarian cancer is one of the leading causes of mortality in women. In 2020, 5,395 (6.2%) of diagnosed malignancies in females were ovarian in origin. It also ranked second among gynecologic malignancies after cervical cancer. The prevalence in Asian /Pacific women is 9.2 per 100,000 population. Increased mortality and poor prognosis in ovarian cancer are caused by asymptomatic growth and delayed or absent symptoms for which about 70% of women have an advanced stage (III/IV) by the time of diagnosis. The most associated gene mutations are Breast Cancer gene 1 (BRCA1) which is identified in chromosome 17q21 and Breast Cancer gene 2 (BRCA2) identified in chromosome 13. Both proteins function in the double-strand DNA break repair pathway especially in the large framework repair molecules. Olaparib is a first-line drug used in the management of ovarian cancer. It targets affected cells by inhibition of poly (ADP-ribose) polymerase (PARP) activity which induces synthetic lethality in mutated BRCA1/2 cancers by selectively targeting tumor cells that fail to repair DNA double-strand breaks (DSBs). OBJECTIVE: The study aims to determine the prevalence of pathogenic somatic mutations in BRCA1 and BRCA2 among patients diagnosed of having ovarian cancer, to characterize the identified variants into benign/ no pathogenic variant identified, variant of uncertain significance (VUS), and pathogenic, and to determine the relationship of specific mutations detected with histomorphologic findings and clinical attributes. METHODOLOGY: Ovarian cancer tissues available at the St. Luke’s Medical Center Human Cancer Biobank and formalin-fixed paraffin-embedded (FFPE) tissue blocks diagnosed as ovarian cancer from the year 2016 to 2020 were included. Determination of the prevalence of somatic BRCA1 and BRCA2 mutations using Next Generation Sequencing (NGS). RESULTS: A total of 60 samples were processed, and three samples were excluded from the analysis due to an inadequate number of cells. In the remaining 57 samples diagnosed ovarian tumors, pathogenic BRCA1/2 variants were identified in 10 (17.5%) samples. Among the BRCA1/2 positive samples, 3 (5.3%) BRCA1 and 7 (12.3%) BRCA2 somatic mutations were identified. CONCLUSION Identification of specific BRCA1/2 mutations in FFPE samples with NGS plays a big role in the management of ovarian cancer, particularly with the use of targeted therapies such as Olaparib. The use of this drug could provide a longer disease-free survival for these patients. Furthermore, we recommend that women diagnosed with ovarian cancer should be subjected to genetic testing regardless of the histologic subtypes or clinical features. Lastly, genetic testing should be done along with proper genetic counseling, especially for patients who are susceptible to these mutations.
ovarian cancer