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  1. Inn FX, Ahmed N, Hing EY, Jasman MH
    Urol Ann, 2017 5 10;9(2):194-196.
    PMID: 28479777 DOI: 10.4103/0974-7796.204178
    Tyrosine kinase inhibitor (TKI) and its side effects are well known. However, these are mainly descriptive, with pictorial data lacking. Here, in we report a case of metastatic renal cell carcinoma, treated with TKI, with classic side effects; supplemented with images that demonstrate the adverse effects of the drug. In addition, we discuss and demonstrate the computed tomography changes.
    Matched MeSH terms: Protein-Tyrosine Kinases
  2. Soria JC, Ohe Y, Vansteenkiste J, Reungwetwattana T, Chewaskulyong B, Lee KH, et al.
    N Engl J Med, 2018 01 11;378(2):113-125.
    PMID: 29151359 DOI: 10.1056/NEJMoa1713137
    BACKGROUND: Osimertinib is an oral, third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) that selectively inhibits both EGFR-TKI-sensitizing and EGFR T790M resistance mutations. We compared osimertinib with standard EGFR-TKIs in patients with previously untreated, EGFR mutation-positive advanced non-small-cell lung cancer (NSCLC).

    METHODS: In this double-blind, phase 3 trial, we randomly assigned 556 patients with previously untreated, EGFR mutation-positive (exon 19 deletion or L858R) advanced NSCLC in a 1:1 ratio to receive either osimertinib (at a dose of 80 mg once daily) or a standard EGFR-TKI (gefitinib at a dose of 250 mg once daily or erlotinib at a dose of 150 mg once daily). The primary end point was investigator-assessed progression-free survival.

    RESULTS: The median progression-free survival was significantly longer with osimertinib than with standard EGFR-TKIs (18.9 months vs. 10.2 months; hazard ratio for disease progression or death, 0.46; 95% confidence interval [CI], 0.37 to 0.57; P<0.001). The objective response rate was similar in the two groups: 80% with osimertinib and 76% with standard EGFR-TKIs (odds ratio, 1.27; 95% CI, 0.85 to 1.90; P=0.24). The median duration of response was 17.2 months (95% CI, 13.8 to 22.0) with osimertinib versus 8.5 months (95% CI, 7.3 to 9.8) with standard EGFR-TKIs. Data on overall survival were immature at the interim analysis (25% maturity). The survival rate at 18 months was 83% (95% CI, 78 to 87) with osimertinib and 71% (95% CI, 65 to 76) with standard EGFR-TKIs (hazard ratio for death, 0.63; 95% CI, 0.45 to 0.88; P=0.007 [nonsignificant in the interim analysis]). Adverse events of grade 3 or higher were less frequent with osimertinib than with standard EGFR-TKIs (34% vs. 45%).

    CONCLUSIONS: Osimertinib showed efficacy superior to that of standard EGFR-TKIs in the first-line treatment of EGFR mutation-positive advanced NSCLC, with a similar safety profile and lower rates of serious adverse events. (Funded by AstraZeneca; FLAURA ClinicalTrials.gov number, NCT02296125 .).

    Matched MeSH terms: Protein-Tyrosine Kinases/antagonists & inhibitors
  3. Omar E, Othman NH
    Med J Malaysia, 2003 Aug;58(3):461-2.
    PMID: 14750392
    Matched MeSH terms: Receptor Protein-Tyrosine Kinases/genetics*
  4. Kuan JW, Melaine Michael S
    Med J Malaysia, 2018 04;73(2):78-85.
    PMID: 29703870 MyJurnal
    OBJECTIVES: There are very few published chronic myeloid leukaemia (CML) epidemiology studies in South-East Asia and no representative from Malaysia.

    METHODS: This is a cross-sectional study of adult CML patients (citizen) in a single but representative centre in southern Sarawak.

    RESULTS: Total 79 patients (Malay 39%, Chinese 30.4%, Iban 17.7%, Bidayuh 12.7%) were identified from the databases. Median age at diagnosis was younger, 40, compared to developed countries due to population structure. M:F ratio was higher, 2.6:1 compared to other countries 1.3-1.7:1. Majority presented at chronic phase (89.5%), low/intermediate risk score (80%) and started imatinib (96%) as first line tyrosine kinase inhibitor (TKI), which 40% of them switched to other TKI due to intolerance (17%) and failure (including disease progression)/not achieving major molecular response (83%). Quantitative polymerase chain reaction (qPCR) assessment after three months of TKI treatment had higher positive predictive value to predict Imatinib failure, 75%, than qPCR assessment after six months of TKI treatment, 58%. Presenting phase, symptoms, signs and laboratory data were like most countries. Estimated prevalence and incidence of CML in southern Sarawak was 69.2/1,000,000 population at the Year 2016 (similar to most developing countries) and 8.0/1,000,000 population per year at the Year 2011-2016 (similar to most countries), respectively. The incidence increased with age and was lowest among Iban, 12.8 and highest among Chinese, 19.5, which was 4x higher than Chinese in China. The prevalence of different BCR-ABL1 transcript type was like other Asia countries CONCLUSION: Significant epidemiological differences on M:F ratio and ethnic groups compared to other countries warrant further study.

    Matched MeSH terms: Protein-Tyrosine Kinases
  5. Lee JS, Choi SJ, Kim L, Park IS, Han JY, Kim JM, et al.
    Malays J Pathol, 2019 Aug;41(2):213-222.
    PMID: 31427559
    INTRODUCTION: Anaplastic lymphoma kinase-positive (ALK+) anaplastic large cell lymphoma (ALCL) with a non-common pattern can be diagnostic challenging. Pathologists can be unavoidably and unintentionally blind to non-descript tumor cells in a lymphohistiocytic- (LH) or small-cell (SC)-pattern. We report a case of primary systemic ALK+ ALCL with a SC pattern that presented as secondary gastric lesions with a mixed LH and SC pattern that was masqueraded as inflammatory lesions.

    CASE REPORT: A 34-year-old woman with intractable epigastric pain was referred to have repeated endoscopy with biopsy. She was found to multiple gastric erosions and nodules that were diagnosed as inflammatory lesions both endoscopically and histologically. Meanwhile, she developed an acute onset of severe back pain associated with a pathologic compression fracture in the T3 thoracic vertebral body. Imaging studies disclosed a disseminated systemic disease involving abdominopelvic lymph nodes and cervical and thoracic vertebral bodies. The needle biopsy of the pelvic lymph node disclosed diffuse proliferation of monomorphic small round cells that were diffusely positive for CD30 and ALK. A diagnosis of ALK+ ALCL with a monomorphic SC pattern was rendered.

    DISCUSSION: A retrospective review of the gastric biopsies with the aid of immunohistochemistry enabled us to recognise the presence of lymphomatous infiltrates with a mixed LH and SC pattern in every piece of gastric biopsies that were repeatedly misdiagnosed as inflammatory lesions. This case illustrates a significant diagnostic pitfall of the LH- and SC-patterns in ALK+ ALCL, in which the tumour cells featuring lymphoid, plasmacytoid or histiocytoid appearance can be masqueraded as inflammatory cells.

    Matched MeSH terms: Receptor Protein-Tyrosine Kinases
  6. Ankathil R, Ismail SM, Mohd Yunus N, Sulong S, Husin A, Abdullah AD, et al.
    Malays J Pathol, 2020 Dec;42(3):307-321.
    PMID: 33361712
    Chronic myeloid leukaemia (CML) provides an illustrative disease model for both molecular pathogenesis of cancer and rational drug therapy. Imatinib mesylate (IM), a BCR-ABL1 targeted tyrosine kinase inhibitor (TKI) drug, is the first line gold standard drug for CML treatment. Conventional cytogenetic analysis (CCA) can identify the standard and variant Philadelphia (Ph) chromosome, and any additional complex chromosome abnormalities at diagnosis as well as during treatment course. Fluorescence in situ hybridization (FISH) is especially important for cells of CML patients with inadequate or inferior quality metaphases or those with variant Ph translocations. CCA in conjunction with FISH can serve as powerful tools in all phases of CML including the diagnosis, prognosis, risk stratification and monitoring of cytogenetic responses to treatment. Molecular techniques such as reverse transcriptase-polymerase chain reaction (RT-PCR) is used for the detection of BCR-ABL1 transcripts at diagnosis whereas quantitative reverse transcriptase-polymerase chain reaction (qRTPCR) is used at the time of diagnosis as well as during TKI therapy for the quantitation of BCR-ABL1 transcripts to evaluate the molecular response and minimal residual disease (MRD). Despite the excellent treatment results obtained after the introduction of TKI drugs, especially Imatinib mesylate (IM), resistance to TKIs develops in approximately 35% - 40% of CML patients on TKI therapy. Since point mutations in BCR-ABL1 are a common cause of IM resistance, mutation analysis is important in IM resistant patients. Mutations are reliably detected by nested PCR amplification of the translocated ABL1 kinase domain followed by direct sequencing of the entire amplified kinase domain. The objective of this review is to highlight the importance of regular and timely CCA, FISH analysis and molecular testing in the diagnosis, prognosis, assessment of therapeutic efficacy, evaluation of MRD and in the detection of BCR-ABL1 kinase mutations which cause therapeutic resistance in adult CML patients.
    Matched MeSH terms: Protein-Tyrosine Kinases/antagonists & inhibitors
  7. Yaakup H, Sagap I, Fadilah SA
    Singapore Med J, 2008 Oct;49(10):e289-92.
    PMID: 18946602
    Primary oesophageal lymphoma is a very rare entity, with fewer than 30 reported cases worldwide. It represents an important cause of dysphagia. Most of the oesophageal lymphomas are diffuse large B-cell type, with only one reported case of anaplastic large cell lymphoma (ALCL) of T-cell phenotype. Primary oesophageal lymphomas that are not associated with an immunocompromised state tend to affect elderly patients. We describe the first case of primary oesophageal Ki (CD30)-positive ALK+ALCL of T-cell phenotype in a 34-year-old immunocompetent woman, who presented with a two-year history of dysphagia. She was treated with chemotherapy and endoscopic oesophageal dilations and stenting, resulting in complete remission of the lymphoma and resolution of the dysphagia. She then underwent autologous peripheral blood haematopoietic stem cell transplantation and remained disease-free two years after the diagnosis.
    Matched MeSH terms: Protein-Tyrosine Kinases/biosynthesis*; Receptor Protein-Tyrosine Kinases
  8. Wan Mohamad Darani WNS, Mat Ruzlin AN, Azhar ZI, Chen XW
    Sci Rep, 2024 Mar 22;14(1):6890.
    PMID: 38519534 DOI: 10.1038/s41598-024-57593-y
    The growing Human Immunodeficiency Virus (HIV) incidences and insufficient HIV knowledge among Malaysian late adolescents necessitate immediate attention to HIV prevention via education. This study aims to develop and validate an Information-Motivation-Behavioural skills (IMB) model-based education kit for adolescents, PREM-Kit, to educate on HIV prevention among Malaysian late adolescents. Utilizing the Analysis, Design, Development, Implementation, and Evaluation model, we conducted the study in three phases: needs assessment, development of PREM-Kit, and validation of PREM-Kit by applying the IMB model to map the PREM-Kit's contents. PREM-Kit, developed in Malay language, consisted of an infographic flip chart and videos. Five multi-disciplinary experts validated the PREM-Kit using the content validity index (CVI), and 13 end-users validated the PREM-Kit using the Malay version of the Patient Education Materials Assessment Tool for Printable and Audiovisual Materials. The infographic flip chart comprised three modules covering 15 topics, and an animated video accompanied each module. PREM-Kit achieved CVI scores of 1.0 and median scores of over 80% for understandability and actionability. Overall, the newly developed IMB model-based HIV education kit has good content validity, is simple to comprehend and apply, and is ready for testing its effectiveness in improving adolescents' knowledge, attitudes, and practices for HIV prevention.
    Matched MeSH terms: Receptor Protein-Tyrosine Kinases
  9. Liam CK, Pang YK, Poh ME, Kow KS, Wong CK, Varughese R
    Respirol Case Rep, 2013 Sep;1(1):20-2.
    PMID: 25473531 DOI: 10.1002/rcr2.14
    Breast metastases from non-small cell lung carcinoma are rarely reported. We report a case of a female patient with primary adenocarcinoma of the lower lobe of her right lung presenting with a massive right-sided malignant pleural effusion. The tumor harbored an epidermal growth factor receptor insertion mutation in exon 20 but was anaplastic lymphoma kinase translocation negative. She did not respond to treatment with erlotinib. First- and second-line cytotoxic chemotherapy resulted in stable disease as the best responses. She developed right breast metastasis 20 months after her initial presentation. The rarity of the condition and the likely mechanism of the breast metastasis are discussed.
    Matched MeSH terms: Receptor Protein-Tyrosine Kinases
  10. Karim ME, Shetty J, Islam RA, Kaiser A, Bakhtiar A, Chowdhury EH
    Pharmaceutics, 2019 Feb 20;11(2).
    PMID: 30791612 DOI: 10.3390/pharmaceutics11020089
    Inorganic nanoparticles hold great potential in the area of precision medicine, particularly for treating cancer owing to their unique physicochemical properties, biocompatibility and improved pharmacokinetics properties compared to their organic counterparts. Here we introduce strontium sulfite nanoparticles as new pH-responsive inorganic nanocarriers for efficient transport of siRNAs into breast cancer cells. We employed the simplest nanoprecipitation method to generate the strontium sulfite nanoparticles (SSNs) and demonstrated the dramatic roles of NaCl and d-glucose in particle growth stabilization in order to produce even smaller nanosize particles (Na-Glc-SSN) with high affinity towards negatively charged siRNA, enabling it to efficiently enter the cancer cells. Moreover, the nanoparticles were found to be degraded with a small drop in pH, suggesting their potential capability to undergo rapid dissolution at endosomal pH so as to release the payload. While these particles were found to be nontoxic to the cells, they showed higher potency in facilitating cancer cell death through intracellular delivery and release of oncogene-specific siRNAs targeting ros1 and egfr1 mRNA transcripts, than the strontium sulfite particles prepared in absence of NaCl and d-glucose, as confirmed by growth inhibition assay. The mouse plasma binding analysis by Q-TOF LC-MS/MS demonstrated less protein binding to smaller particles of Na-Glc-SSNs. The biodistribution studies of the particles after 4 h of treatment showed Na-Glc-SSNs had less off-target distribution than SSNs, and after 24 h, all siRNAs were cleared from all major organs except the tumors. ROS1 siRNA with its potential therapeutic role in treating 4T1-induced breast tumor was selected for subsequent in vivo tumor regression study, revealing that ROS1 siRNA-loaded SSNs exerted more significant anti-tumor effects than Na-Glc-SSNs carrying the same siRNA following intravenous administration, without any systemic toxicity. Thus, strontium sulfite emerged as a powerful siRNA delivery tool with potential applications in cancer gene therapy.
    Matched MeSH terms: Protein-Tyrosine Kinases
  11. Mphahlele MJ, Paumo HK, Choong YS
    Pharmaceuticals (Basel), 2017 Nov 20;10(4).
    PMID: 29156606 DOI: 10.3390/ph10040087
    Series of the 2-unsubstituted and 2-(4-chlorophenyl)-substituted 4-anilino-6-bromoquinazolines and their 6-(4-fluorophenyl)-substituted derivatives were evaluated for in vitro cytotoxicity against MCF-7 and HeLa cells. The 2-unsubstituted 4-anilino-6-bromoquinazolines lacked activity, whereas most of their 2-(4-chlorophenyl) substituted derivatives were found to exhibit significant cytotoxicity and selectivity against HeLa cells. Replacement of bromine with 4-fluorophenyl group for the 2-unsubstituted 4-anilinoquinazolines resulted in superior activity against HeLa cells compared to Gefitinib. The presence of a 4-fluorophenyl group in the 2-(4-chlorophenyl) substituted derivatives led to increased cytotoxicity against HeLa cells, except for the 3-chloroanilino derivative. The most active compounds, namely, 3g, 3l, and 4l, were found to exhibit a moderate to significant inhibitory effect against epidermal growth factor receptor tyrosine kinase (EGFR-TK). The EGFR molecular docking model suggested that these compounds are nicely bound to the region of EGFR.
    Matched MeSH terms: Receptor Protein-Tyrosine Kinases
  12. Omar E, Madhavan M, Othman NH
    Pathology, 2004 Apr;36(2):152-9.
    PMID: 15203751
    To investigate RET and p53 expression in local thyroid lesions, in order to shed light on the pathogenesis of papillary carcinoma and explain the high prevalence of this condition among the nodular hyperplasia (multi-nodular goitre) cases.
    Matched MeSH terms: Receptor Protein-Tyrosine Kinases/metabolism*
  13. Tai YC, Kim LH, Peh SC
    Pathology, 2003 Oct;35(5):436-43.
    PMID: 14555389
    AIMS: The most common recurrent genetic aberration in anaplastic large cell lymphoma (ALCL) is translocation involving the ALK gene that results in ectopic expression of ALK protein in lymphoid tissue. This study aims to investigate the frequency of ALK gene rearrangement in a series of Asian ALCL.

    METHODS: ALK gene rearrangement was detected by immunostaining of ALK protein and fluorescence in situ hybridisation (FISH) targeting at the 2p23 region.

    RESULTS: The expression of ALK protein was detected in 24/34 (71%) of the cases, and it was significantly higher in childhood cases (100%) when compared to adult cases (47%). The analyses by FISH were consistent with the results from immunostaining of ALK protein, but the analyses were only successful in 15/34 (44%) cases. FISH analyses detected extra copies of ALK gene in three cases, including one case that expressed ALK protein and showed 2p23 rearrangement.

    CONCLUSIONS: The current series revealed a high frequency of ALK gene rearrangement, especially in the children. Immunostaining of ALK protein is a reliable indication of ALK gene rearrangement, and is superior to FISH. However, FISH analysis is useful in detecting other genetic aberrations that are not related to ALK gene rearrangement.

    Matched MeSH terms: Protein-Tyrosine Kinases/genetics*; Protein-Tyrosine Kinases/metabolism; Receptor Protein-Tyrosine Kinases
  14. Sosroseno W, Barid I, Herminajeng E, Susilowati H
    Oral Microbiol. Immunol., 2002 Apr;17(2):72-8.
    PMID: 11929552
    The aim of this study was to determine whether Actinobacillus actinomycetemcomitans lipopolysaccharide (LPS-A. actinomycetemcomitans) could stimulate a murine macrophage cell line (RAW264.7 cells) to produce nitric oxide (NO). The cells were treated with LPS-A. actinomycetemcomitans or Escherichia coli LPS (LPS-Ec) for 24 h. The effects of N(G)-monomethyl-L-arginine (NMMA), polymyxin B and cytokines (IFN-gamma, TNF-alpha, IL-4 and IL-12) on the production of NO were also determined. The role of protein tyrosine kinase, protein kinase C and microtubulin organization on NO production were assessed by incubating RAW264.7 cells with genistein, bisindolylmaleide and colchicine prior to LPS-A. actinomycetemcomitans stimulation, respectively. NO levels from the culture supernatants were determined by the Griess reaction. The results showed that LPS-A. actinomycetemcomitans stimulated NO production by RAW264.7 cells in a dose-dependent manner, but was slightly less potent than LPS-Ec. NMMA and polymyxin B blocked the production of NO. IFN-gamma and IL-12 potentiated but IL-4 depressed NO production by LPS-A. actinomycetemcomitans-stimulated RAW264.7 cells. TNF-alpha had no effects on NO production. Genistein and bisindolylmalemaide, but not colchicine, reduced the production of NO in a dose-dependent mechanism. The results of the present study suggest that A. actinomycetemcomitans LPS, via the activation of protein tyrosine kinase and protein kinase C and the regulatory control of cytokines, stimulates NO production by murine macrophages.
    Matched MeSH terms: Protein-Tyrosine Kinases/antagonists & inhibitors
  15. Zakaria Z, Zulkifle MF, Wan Hasan WAN, Azhari AK, Abdul Raub SH, Eswaran J, et al.
    Onco Targets Ther, 2019;12:7749-7756.
    PMID: 31571924 DOI: 10.2147/OTT.S214611
    Background: Epidermal growth factor receptor (EGFR) is a member of the ErbB family of tyrosine kinase receptor proteins that plays important roles in tumour cell survival and proliferation. EGFR has been reported to be overexpressed in up to 78% of triple-negative breast cancer (TNBC) cases suggesting it as a potential therapeutic target. The clinical trials of anti-EGFR agents in breast cancer showed low response rates. However, a subgroup of patients demonstrated response to EGFR inhibitors highlighting the necessity to stratify patients, who might benefit from effective combination therapy that could include anti EGFR-agents. Population variability in EGFR expression warrants systematic evaluation in specific populations.

    Purpose: To study EGFR alterations and expressions in a multi ethnic Malaysian TNBC patient cohort to determine the possibility of using anti-EGFR combinatorial therapy for this population.

    Patients and methods: In this study, we evaluated 58 cases of Malaysian TNBC patient samples for EGFR gene copy number alteration and EGFR protein overexpression using fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) methods, respectively.

    Results: EGFR protein overexpression was observed in about 30% while 15.5% displayed high EGFR copy number including 5.17% gene amplification and over 10% high polysomy. There is a positive correlation between EGFR protein overexpression and gene copy number and over expression of EGFR is observed in ten out of the 48 low copy number cases (20.9%) without gene amplification.

    Conclusion: This study provides the first glimpse of EGFR alterations and expressions in a multi ethnic Malaysian TNBC patient cohort emphasising the need for the nationwide large scale EGFR expression evaluation in Malaysia.

    Matched MeSH terms: Receptor Protein-Tyrosine Kinases
  16. Issac PK, Guru A, Chandrakumar SS, Lite C, Saraswathi NT, Arasu MV, et al.
    Mol Biol Rep, 2020 Sep;47(9):6727-6740.
    PMID: 32809102 DOI: 10.1007/s11033-020-05728-5
    Understanding the mechanism by which the exogenous biomolecule modulates the GLUT-4 signalling cascade along with the information on glucose metabolism is essential for finding solutions to increasing cases of diabetes and metabolic disease. This study aimed at investigating the effect of hamamelitannin on glycogen synthesis in an insulin resistance model using L6 myotubes. Glucose uptake was determined using 2-deoxy-D-[1-3H] glucose and glycogen synthesis were also estimated in L6 myotubes. The expression levels of key genes and proteins involved in the insulin-signaling pathway were determined using real-time PCR and western blot techniques. The cells treated with various concentrations of hamamelitannin (20 µM to 100 µM) for 24 h showed that, the exposure of hamamelitannin was not cytotoxic to L6 myotubes. Further the 2-deoxy-D-[1-3H] glucose uptake assay was carried out in the presence of wortmannin and Genistein inhibitor for studying the GLUT-4 dependent cell surface recruitment. Hamamelitannin exhibited anti-diabetic activity by displaying a significant increase in glucose uptake (125.1%) and glycogen storage (8.7 mM) in a dose-dependent manner. The optimum concentration evincing maximum activity was found to be 100 µm. In addition, the expression of key genes and proteins involved in the insulin signaling pathway was studied to be upregulated by hamamelitannin treatment. Western blot analysis confirmed the translocation of GLUT-4 protein from an intracellular pool to the plasma membrane. Therefore, it can be conceived that hamamelitannin exhibited an insulinomimetic effect by enhancing the glucose uptake and its further conversion into glycogen by regulating glucose metabolism.
    Matched MeSH terms: Protein-Tyrosine Kinases/genetics; Protein-Tyrosine Kinases/metabolism
  17. Siti-Aishah, M.A., Salwati, S., Idrus, M., Rahimah, R., Salmi, A., Leong, C.F., et al.
    Medicine & Health, 2008;3(1):69-74.
    MyJurnal
    Anaplastic large cell lymphoma (ALCL) is a rare tumour, accounting for approximately 3% of adult non-Hodgkin lymphomas.1 Primary systemic ALCL frequently involves both lymph nodes and extranodal sites. A 44-year-old woman presented with a firm, mobile mass in the left iliac fossa region. Ultrasound findings showed a well defined inhomogenous soft tissue mass, measuring 4x4x2.6cm in the deep subcutaneous region. Histopathological examination revealed that the mass was infiltrated by large lymphoid cells with marked nuclear atypia including kidney-shaped nuclei. These neoplastic cells expressed anaplastic lymphoma kinase (ALK) (both nuclear & cytoplasmic staining), CD30 and EMA but not for T-cell (CD45RO and CD3), and B-cell (CD20 & CD79α) markers. Fluorescence in situ hybridization (FISH) analysis showed a t(2;5)(p23;q35) chromosomal translocation. Subsequently the patient developed shortness of the breath and a thoracic computed tomography (CT) scan showed a mass encasing the right upper lobe bronchus. She also had bilateral axillary lymph nodes, measuring 1 cm in diameter (biopsy was not done). The mediastinum and endobronchial region did not show any abnormalities. She received 6 cycles of CHOP chemotherapy and remained disease free 2 years after diagnosis. ALCL, rarely present as a soft tissue tumour and this disease should be included as a differential diagnosis of any soft tissue mass.
    Matched MeSH terms: Receptor Protein-Tyrosine Kinases
  18. Hooi Yeen Yap, Jack Bee Chook, Sin Yeang Teow
    MyJurnal
    ntroduction: Nasopharyngeal carcinoma (NPC) is a prevalent cancer among human population in Southern China, Hong Kong and Southeast Asia. In Malaysia, NPC is the fourth most common cancer in both sexes, predominantly in the Chinese. Epstein-Barr virus (EBV) infection is known to be highly associated with NPC. Fibroblast growth factor receptor-4 (FGFR4) is part of the family of tyrosine kinase receptors that regulate cell survival, differentiation and pro-liferation. The binding of FGFR4 ligands such as fibroblasts growth factors (FGFs) has been shown to activate various oncogenic signalling pathway including MAPK, Ras and PI3K-Akt pathways. In the past, FGFR4 has been shown to promote tumorigenesis and tumour progression in various cancers such as liver, colon, breast and pancreatic and gastric cancers. However, its role in NPC establishment and pathogenesis is under-explored. This study aimed to evaluate the FGFR4 expression in NPC using various cell lines and its potential as a therapeutic target for NPC treat-ment by gene silencing. Methods: The basal FGFR4 level of NPC (EBV-positive: C666-1 and EBV-negative: HONE1 and HK1) and nasopharyngeal epithelial (NPE) normal (NP69 and NP460) cell lines was determined by western blot analysis and RT-qPCR. FGFR4 level at different time points (0, 24, 48, and 72 hours) in HONE1 and C666-1 cell lines were determined by western blot analysis. Luminescence-based assay was performed to determine the cell prolifer-ation of NPC cells in correlation with the FGFR4 expression. NPC cells were then treated with the optimised FGFR4 siRNA or FGFR inhibitor, BLU-9931 and the silencing/ inhibition of FGFR4 expression was confirmed by western blot analysis. The effect of FGFR4 inhibition on the cell proliferation and aggressiveness of NPC cells was then investigat-ed through wound healing assay and invasion marker analysis. Results: Out of the five tested cell lines, HONE1 and C666-1 highly expressed FGFR4, NP69 showed very low expression while HK1 and NP460 did not express FGFR4. In the time-point study, the FGFR4 level of HONE1 and C666-1 peaked at 24-48 hours which is the exponential phase of cells. Following that, the FGFR4 level decreased corresponding to the decreased cell growth rate due to the nutrient deprivation. siRNA experiments showed that 6.25nM of four siRNAs (5, 6, 9 and 10) could effectively target and silence the FGFR4 expression of HONE1, but not in C666-1 even up to 250nM was tested. When BLU-9931 was used, only modest inhibition was observed in both cells at 3uM. Compared to the untreated control, FGFR4-inhibited HONE1 exhibited decreased cell proliferation rate. Cell migration and invasion capabilities of HONE1 were also significantly reduced following the FGFR4 silencing, suggesting the potential of utilising FGFR4 as the therapeutic target. Conclusion: FGFR4 is highly expressed in C666-1 (EBV-positive) and HONE1 (initially EBV-positive, but lost EBV genome in subsequent in vitro passage) NPC cells, but not in EBV-negative HK1 NPC cell and normal NPE cells. FGFR4 gene silencing effectively inhibited the cell proliferation, migration and invasive potentials of NPC cell line. These findings highlight the therapeutic value of targeting FGFR4 for NPC treatment. Further investigations are war-ranted to reveal the molecular mechanism and the possible role of EBV in regulating FGFR4 pathway.
    Matched MeSH terms: Receptor Protein-Tyrosine Kinases
  19. Poh ME, Liam CK, Rajadurai P, Chai CS
    J Thorac Dis, 2018 Jul;10(7):E560-E563.
    PMID: 30174934 DOI: 10.21037/jtd.2018.06.122
    We report the first case of epithelial-to-mesenchymal transition (EMT) as the cause of acquired resistance to the second-generation EGFR-tyrosine kinase inhibitor (TKI), afatinib in a patient with advanced non-small cell lung cancer (NSCLC) harboring a sensitizing EGFR mutation. Patients with EGFR-mutant NSCLC inevitably develop acquired resistance while on EGFR-TKI treatment. EMT which renders cancer cells more invasive and migratory is one of the mechanisms of acquired resistance to EGFR-TKIs and correlates with a poor prognosis. Possible therapeutic strategies in patients with EMT include blocking M2 muscarinic receptor signalling, targeting EMT with histone deacetylase inhibitors such as entinostat and MEK-inhibitors such as selumetinib, inhibition of microRNAs, immunotherapy and inhibiting fibroblast growth factor receptor-1.
    Matched MeSH terms: Protein-Tyrosine Kinases
  20. Tablit S, Krache R, Amroune S, Jawaid M, Hachaichi A, Ismail AS, et al.
    J Mech Behav Biomed Mater, 2024 Apr;152:106438.
    PMID: 38359736 DOI: 10.1016/j.jmbbm.2024.106438
    Arundo donax L. is investigated in this study as a suitable reinforcing agent for PLA/PP waste blend 3D printing filament. To improve the compatibility of the fibre and polymer, the Arundo fibre was chemically modified using alkali and silane treatment. Untreated and treated fibres were extruded with Polymer blends before being 3D printed. Effect of chemical treatment on thermal, mechanical, and morphological properties of the composites was investigated. The tensile, Izod impact, and water absorption of the 3D printed specimens were also tested. The Alkali treated (ALK) and combination of alkali and silane treatment (SLN) composites displayed good results. Tensile strength and modulus of the materials increased, as well as their maintained stability in the Izod impact test, demonstrating that the incorporation of ArF did not result in a loss in performance. SEM examination supported these findings by confirming the creation of beneficial interfacial contacts between the matrix and fibre components, as demonstrated by the lack of void between the matrix and the fibre surface. Furthermore, the alkali treatment of the ArF resulted in a considerable reduction in water absorption inside the biocomposite, with a 64% reduction seen in ALK composite comparison to the untreated composite (Un). After the 43-day assessment period.
    Matched MeSH terms: Receptor Protein-Tyrosine Kinases
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