1.IsomiRs have functional importance
The Malaysian Journal of Pathology 2015;37(2):73-81
Since the inception of deep sequencing, isomiRs are consistently observed to be produced by most
miRNA genes in a variety of cell types. IsomiRs appear as a variation in length from the canonical
sequence annotated in miRBase, due to an addition or deletion of one or more nucleotides at the
5’ or 3’ ends or both. As the seed sequence is located at the 5’ end of the microRNA, the target
mRNA will be theoretically different. Therefore, 5’isomiRs might potentially target a new set mRNA
compared to their canonical counterpart. This article gives an overview of investigations that explored
the functional potential of isomiRs such as their ability to incorporate into Argonaute protein, the
differential expression of isomiRs in various tissue types and cell lines, and the differences of
mRNA targets between isomiR and its canonical microRNA. In addition, this article provides a
brief introduction of RNA sponges as a potential way to inhibit isomiRs.
2.MicroRNA-induced pluripotent stem cells.
The Malaysian Journal of Pathology 2012;34(2):167-8; author reply 169
3.An immunohistochemical study of Toll-like receptors 2 and 4 in placenta with and without infection
Abdul Rahman Hayati ; Abdulwakil Elraied Mohamed ; Geok Chin Tan
The Malaysian Journal of Pathology 2010;32(1):13-19
Objective: The placenta constitutes a physical and immunological barrier against infectious agents.
Toll-like receptors (TLRs) are essential components for the induction of innate immunity responses in
different human tissues including the placenta. We investigated the expressions of TLR2 and TLR4 in
the decidua and amniotic cells in non-infl amed placenta and placenta with infection. Materials and
Methods: There were a total 74 placentas (37 with infection and 37 without infection- 25 bacterial,
10 viral and 2 toxoplasma). TLR2 and TLR4 expressions were assessed using immunohistochemical
technique. Positive cells were indicated by cytoplasmic staining and the percentage of positive
in 100 cells was recorded and graded. The grades were 1+ (<25%), 2+ (25-75%) and 3+ (>75%).
Results: We found signifi cantly higher expression of TLR2 in the amniotic cells and decidua cells
in infected placentas as compared to non-infl amed placentas among the preterm placenta. A higher
number of cases have TLR4 expression in the amnion of preterm infected placenta than in term
placenta. This, however, is not statistically signifi cant. Conclusion: Our fi ndings suggest that TLR2
plays a role in the innate immunity in bacterial and viral infection in the placenta, however, their
role in protection against toxoplasma may be limited. This study further supports the observations
that TLR2 expression was higher in placenta with infection which strengthened the role of TLR2
in the protection of preterm placenta against infection.
5.Construction of a doxycycline inducible lentivirus that expresses stem cell-specific miR-302 cluster
The Malaysian Journal of Pathology 2020;42(1):91-97
Introduction: The polycistronic miR-302 cluster encodes five miRNA genes that have an important role in the regulation of embryonic stem cell function. Studies showed that the miR-302 cluster can reprogram both mouse and human fibroblasts to induced pluripotent stem cells (iPSCs) with high efficiency. The aim of this study was to generate an inducible lentivirus that expresses miR-302 cluster in order to further investigate somatic cell reprogramming by these miRNAs. Materials and Methods: The miR-302 cluster was amplified by polymerase chain reaction technique from human genomic DNA and was ligated into pTRIPz, an inducible lentiviral vector. Results: MRC5 fibroblasts and HEK293 (human embryonic kidney) cells were infected with pTRIPz-302 cluster lentivirus and the family of 302 miRNAs were strongly expressed in HEK293 cells but lowly expressed in MRC5 fibroblasts. When cultured in hESC conditions, MRC5 cells expressed only low levels of DNMT3B, Nanog, Oct4 and Lin28 and failed to show stem cell induction. The red fluorescent expression seen in the majority of MRC5 cells, indicated that the rate of infection by lentivirus was efficient. Discussion: The efficiency of reprogramming may be improved perhaps by either using a different cell type or a high expression vector with a different type of promoter.
6.Beta-human Chorionic Gonadotropin-secreting Lung Adenocarcinoma
Yin Ping Wong ; Geok Chin Tan ; Suraya Aziz ; Sucharit Pongprakyun ; Fuad Ismail
Malaysian Journal of Medical Sciences 2015;22(4):76-80
Overexpression of beta-human chorionic gonadotropin (β-hCG) is frequently associated with germ cell tumours, especially choriocarcinoma. Ectopic secretion of β-hCG by non-small cell lung cancer is exceptional. We present an exceedingly rare case of pulmonary adenocarcinoma that secretes β-hCG. Our patient is a 62-year-old postmenopausal woman, a nonsmoker, who presented with a six-month history of progressive dyspnoea, associated with decreased appetite and significant weight loss. Her serum β-hCG was very high (11211.9 mIU/ml), which prompted investigations to exclude germ cell tumour. Radiological imaging revealed a 10-cm right lung mass with adrenal metastasis. No other focal lesions were detected. Microscopy of the lung biopsy specimen showed replacement of normal lung tissue by sheets of malignant cells, forming vague glands in some areas. Immunohistochemically, the malignant cells showed focal immunopositivity for thyroid transcription factor 1 (TTF-1), napsin A, cytokeratin 7 (CK7) and β-hCG. A diagnosis of β-hCG-secreting pulmonary poorly differentiated adenocarcinoma was rendered. Serum β-hCG level decreased significantly to 168.6 mIU/ml after the first cycle of chemotherapy. In conclusion, β-hCG expression in lung cancer should be recognised to facilitate prompt diagnosis and initiation of appropriate intervention.
7.CNS germinoma with extensive calcification: An unusual histologic finding
The Malaysian Journal of Pathology 2019;41(1):71-73
Introduction: Intratumoral calcification is a feature that is more often observed in pineal parenchymal tumour than germinoma. We describe a 13-year-old male with pineal region germinoma demonstrating extensive intratumoral calcification. Case report: He presented with worsening headache that was associated with fatigue, nausea and vomiting. Radiologic examination revealed a multilobular mass in the pineal region with internal calcifications. Biopsy showed a pure germinoma with unusually extensive calcification. Discussion: Although a diagnosis may be suggested with a careful evaluation of imaging, there is no pathognomonic pattern. Thus, histologic verification is necessary for most pineal region masses.
Germinoma
8.Myeloid sarcoma of the urinary bladder with cutaneous tumour seeding after percutaneous suprapubic catheterization
Geok Chin TAN ; Masir NORAIDAH ; Noor HAMIDAH Hussin ; Mohd Sidik SHIRAN ; Boon Cheok LEE ; Thean Yean KEW
The Malaysian Journal of Pathology 2011;33(1):47-51
Myeloid sarcoma (MS) is a rare extramedullary myeloid tumour. It has been reported in various
sites, including lymph node, bone, skin, soft tissue, various organs and the CNS. It may precede
or occur concurrently with acute myeloid leukemia. Urinary bladder involvement is extremely
uncommon. We report a 70-year-old female who had MS of the urinary bladder, presented with
frank and persistent hematuria associated with lower abdominal pain. She subsequently had tumour
seeding in the abdominal skin via percutaneous suprapubic catheter. Tumours from both the urinary
bladder and skin showed immature cells that were immunoreactive toward LCA (focal), MPO (strong),
CD99 (weak) and CD117 (weak). Summary of cases in the literature is presented. The potential of
its misdiagnosis and the useful markers for the diagnosis of MS are discussed
9.Comparative aspects of microRNA expression in canine and human cancers
Kabiru SAHABI ; Gayathri T SELVARAJAH ; Rasedee ABDULLAH ; Yoke Kqueen CHEAH ; Geok Chin TAN
Journal of Veterinary Science 2018;19(2):162-171
MicroRNAs (miRNAs) have important roles in all biological pathways in multicellular organisms. Over 1,400 human miRNAs have been identified, and many are conserved among vertebrates and invertebrates. Regulation of miRNA is the most common mode of post-transcriptional gene regulation. The miRNAs that are involved in the initiation and progression of cancers are termed oncomiRs and several of them have been identified in canine and human cancers. Similarly, several miRNAs have been reported to be down-regulated in cancers of the two species. In this review, current information on the expression and roles of miRNAs in oncogenesis and progression of human and canine cancers, as well the roles miRNAs have in cancer stem cell biology, are highlighted. The potential for the use of miRNAs as therapeutic targets in personalized cancer therapy in domestic dogs and their possible application in human cancer counterparts are also discussed.
Animals
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Biology
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Carcinogenesis
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Dogs
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Gene Expression
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Humans
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Invertebrates
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MicroRNAs
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Neoplastic Stem Cells
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Stem Cells
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Vertebrates
10.The spectrum of pathological findings of tonsils in children: A clinicopathological review
Geok Chin TAN ; Melissa STALLING ; Sura AL-RAWABDEH ; Basil M KAHWASH ; Razan F ALKHOURY ; Samir B KAHWASH
The Malaysian Journal of Pathology 2018;40(1):11-26
Tonsillectomy is among the most commonly performed operations in children. Although follicular lymphoid hyperplasia is usually the main and only pathologic finding at microscopic examination, a variety of other rare but important pathologic changes may be encountered. This review aims to provide an inclusive practical resource and reference for both training and practising pathologists. It discusses the spectrum of pathologic findings, including both neoplastic and non-neoplastic conditions and provides illustrative images.
Tonsil