Malaysian Journal of Pathology最新文献

No abstract available.

Conventionally, megakaryocytes (MKs) are regarded as platelet-producing cells and their platelet-related functions in haemostasis have been well documented. However, it is increasingly evident that MKs have functions beyond platelet production. Convincing findings suggest that MKs are active participants in immunity and infections. Many reviews in the published literature have examined the immune functions of MK-derived platelets. However, relatively few reviews have emphasised on the role of MKs as immune cells. This review gives an overview of MKs, megakaryopoiesis and thrombocytopoiesis, as well as a thorough examination of the evidence that favours MKs as immune cells. The emerging and multifaceted contributions of MKs to host defence against various infections are also discussed. Together, these findings identify MKs as key players in both immune homeostasis and host-pathogen interactions, presenting new therapeutic opportunities.

No abstract available.

No abstract available.

Introduction: Oral cancer is considered the sixth most common form of cancer worldwide. It causes significant morbidity and mortality, especially in low socioeconomic status groups. However, Cancer chemoprevention encompasses the use of specific compounds to suppress the growth of tumours or inhibit carcinogenesis. Natural products have been identified as one of the most significant sources of anti-cancer agents. Meanwhile, several synthetic drugs exhibit potential cytotoxicity and can induce a wide range of degenerative diseases.

Aim of the review: This review aims to determine the various plants, vegetables, and fruits possessing natural chemotherapeutic agents against oral cancer cells.

Materials and methods: A comprehensive review of findings reported in articles retrieved from searches of computerised databases, hand searches, and authoritative texts. Inclusion databases include PubMed, Medline, Web of Science, Scopus, and Scientific. Exclusion Computerised databases: Wikipedia or unknown sources.

Results: Natural products have fewer side effects, high selectivity, low toxicity, and eliminate cancer cells. Thus, the application of natural products as alternative oral and other cancer therapies has recently demonstrated remarkable progress.

Conclusion: Natural products have been widely used in developing oral anti-cancer drugs. Most of these natural products present bioactive chemical agents and novel mechanisms of action, such as the inhibition of tumour cell growth, the induction of apoptosis, DNA damage, and the inhibition of topoisomerases I and II. In future, the successful integration of natural products in oral cancer chemoprevention field depends on the advancement of molecular targeting, personalised approaches, and the exploration of novel drug delivery systems. Furthermore, integration of preclinical findings in clinical trials will be important for translating research into impactful interventions.

Introduction: The emergence of mutations in the BCR::ABL1 kinase domain (KD) impairs imatinib mesylate (IM) binding capacity, thus contributing to IM resistance. Identification of these mutations is important for treatment decisions and precision medicine in chronic myeloid leukaemia (CML) patients. Our study aims to determine the frequency of BCR::ABL1 KD mutations in CML patients with IM resistance.

Materials and methods: Twenty three CML patients (26.7%) showed to have BCR:ABL1 KD mutations with IM resistance.

Results: A total of 14 different types of mutations were identified which are Y253H, E255K, T267A, A287T, M290R, F3111, T3151, F317L, F359V, F3591, F359C, K357T, A399T, E459K and two novel mutations; M290R and K357T. We also discovered two silent mutations at codons 389 and 401.

Conclusion: Mutational analysis is recommended to identify patients at risk of disease progression. Therefore, early detection of such mutations may allow timely treatment intervention to prevent or overcome resistance.

Introduction: The current first-line therapy for nasopharyngeal carcinoma (NPC) is often associated with long-term complications. Oncolytic measles virus (MV) therapy offers a promising alternative to cancer therapy. This study aims to investigate the efficacy of MV in killing NPC cells in vitro, both with or without resistance to radiation and drug therapy.

Materials and methods: NPC cell lines, CNE-1, CNE-2, HONE-1 and C666-1, were exposed to repeated cycles of gamma-irradiation and cisplatin to establish radio- and chemo-resistant cell lines, respectively. The expression of MV receptors, CD46 and nectin-4, were assessed with flow cytometer. To test the efficacy of viral infection, parental and both resistant NPC cells were infected with Measles-GFP-NIS in vitro. The progress of syncytia spread on NPC cells was monitored with fluorescence microscopy up to 60-hours post-infection (p.i.). MV-mediated killing was assessed using tetrazolium-based cell viability assay.

Results: We established cisplatin-resistant (CR) NPC cell lines that exhibit more than two-fold shift in IC50 against cisplatin. Only CNE-2 and C666-1 acquired resistant traits after a cumulative 60-Gy gamma irradiation. All untreated parental and resistant NPCs expressed CD46 but not nectin-4 on their cell surface and were susceptible to MV infection. Syncytia were observable as early as 24 hours p.i. and cell loss was observable at 48-hours p.i. onwards. Interestingly, Measles-GFP-NIS shows higher infectivity in NPC with resistance phenotypes, except in CR-C666-1, and were killed more compared to their non-resistant counterparts.

Conclusion: Measles-GFP-NIS demonstrated potential as an alternative treatment in relapse, recurrent, or advanced stage NPC which often exhibits resistance towards chemo- and radiotherapy.

Introduction: Candida albicans and Streptococcus mutans co-exist in biofilms in the oral cavity. In this study, the impact of S. mutans on the growth of C. albicans within a mixed-species biofilm was examined.

Materials and methods: Single species C. albicans biofilms and mixed species biofilms containing C. albicans and S. mutans at 1:3 and 1:10 ratios were constructed in 6-well microtiter plates. After 24 hours of incubation, the density of resuspended biofilm cells was determined as CFU/ml and used to compare the growth of C. albicans in single species and mixed species biofilms.

Results: The CFU/ml of C. albicans in mixed-species biofilms was found to be higher than that in single-species biofilms.

Conclusion: S. mutans promotes the growth of C. albicans in a co-inhabited biofilm.

Introduction: Leukaemia is the most common cancer in children, however, there is still a big gap in knowledge about the genomic alterations in childhood acute myeloid leukaemia (AML) compared to adult AML. Relapsed AML remains as a leading cause of cancer deaths among children. This study aims to understand the molecular mechanisms of relapsed AML by elucidating the mutational landscape before and during relapse.

Materials and methods: Whole genome sequencing was performed on matched samples collected at diagnosis, remission and relapse from three patients of de novo childhood AML. Sanger sequencing was performed for validation in 47 patients' samples, followed by functional analysis.

Results: Overall, we identified 312 somatic mutations including synonymous single nucleotide variants (SNVs), missense SNVs, deletions and insertion frameshifts, stopgains and splice sites. After prioritisation, only 46 variants were present at diagnosis (13-17 mutations per patient) and 49 variants at relapse (12-20 mutations per patient). Out of 81 variants, there were 35 new variants detected at relapse but not present at diagnosis. Six potential driver mutations (KIT, CDC73, HNF1A, RBM10, ZMYM4 and ETV6) were identified in predicting relapse for the 3 patients, with recurrent mutations of the ETV6 gene in 2 patients. Functional analysis of the ETV6 mutation showed that ETV6 lost its tumour suppressive function when both mutant ETV6 p.P25fs and ETV6 p.N75fs were tested in vitro.

Conclusion: This study has uncovered the mutational landscape in three local childhood AML patients and contributes to a better understanding of the molecular mechanisms of relapsed AML.

No abstract available.