Displaying publications 1 - 20 of 32 in total

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  1. Othman N, Nagoor NH
    Int J Oncol, 2017 Dec;51(6):1757-1764.
    PMID: 29075783 DOI: 10.3892/ijo.2017.4174
    Lung cancer remains a major health problem with a low 5-year survival rate of patients. Recent studies have shown that dysregulation of microRNAs (miRNAs) are prevalent in lung cancer and these aberrations play a significant role in the progression of tumour progression. In the present study, bioinformatics analyses was employed to predict potential miR-608 targets, which are associated with signaling pathways involved in cancer. Luciferase reporter assay identified AKT2 as a novel target of miR-608, and suppression of its protein levels was validated through western blot analysis. Zebrafish embryos were microinjected with cells transfected with miR-608 to elucidate the role of miR-608 in vivo, and immunostained with antibodies to detect activated caspase-3. We present the first evidence that miR-608 behaves as a tumour suppressor in A549 and SK-LU-1 cells through the regulation of AKT2, suggesting that selective targeting of AKT2 via miR-608 may be developed as a potential therapeutic strategy for miRNA-based non-small cell lung cancer (NSCLC) therapy.
    Matched MeSH terms: Heterografts
  2. Papadaki V, Asada K, Watson JK, Tamura T, Leung A, Hopkins J, et al.
    Cancers (Basel), 2020 Nov 13;12(11).
    PMID: 33202923 DOI: 10.3390/cancers12113362
    Osteomodulin (OMD) and proline/arginine-rich end leucine repeat protein (PRELP) are secreted extracellular matrix proteins belonging to the small leucine-rich proteoglycans family. We found that OMD and PRELP were specifically expressed in umbrella cells in bladder epithelia, and their expression levels were dramatically downregulated in all bladder cancers from very early stages and various epithelial cancers. Our in vitro studies including gene expression profiling using bladder cancer cell lines revealed that OMD or PRELP application suppressed the cancer progression by inhibiting TGF-β and EGF pathways, which reversed epithelial-mesenchymal transition (EMT), activated cell-cell adhesion, and inhibited various oncogenic pathways. Furthermore, the overexpression of OMD in bladder cancer cells strongly inhibited the anchorage-independent growth and tumorigenicity in mouse xenograft studies. On the other hand, we found that in the bladder epithelia, the knockout mice of OMD and/or PRELP gene caused partial EMT and a loss of tight junctions of the umbrella cells and resulted in formation of a bladder carcinoma in situ-like structure by spontaneous breakdowns of the umbrella cell layer. Furthermore, the ontological analysis of the expression profiling of an OMD knockout mouse bladder demonstrated very high similarity with those obtained from human bladder cancers. Our data indicate that OMD and PRELP are endogenous inhibitors of cancer initiation and progression by controlling EMT. OMD and/or PRELP may have potential for the treatment of bladder cancer.
    Matched MeSH terms: Heterografts
  3. Yehya AHS, Asif M, Kaur G, Hassan LEA, Al-Suede FSR, Abdul Majid AMS, et al.
    J Adv Res, 2019 Jan;15:59-68.
    PMID: 30581613 DOI: 10.1016/j.jare.2018.05.006
    Pancreatic cancer has the highest mortality rate among cancers due to its aggressive biology and lack of effective treatment. Gemcitabine, the first line anticancer drug has reduced efficacy due to acquired resistance. The current study evaluates the toxicological effects of Orthosiphon stamineus (O.s) and its marker compound (rosmarinic acid) in combination with gemcitabine. O.s (200 or 400 mg/kg/day) and rosmarinic acid (32 mg/kg/day) were administered orally and gemcitabine (10 mg/kg/3 days) intraperitoneally either alone or in combination treatment for fourteen days. Parameters including blood serum biochemistry, hematology, myeloid-erythroid ratio, incident of lethality, and histopathological analysis of liver, kidney, and spleen tissues were studied. Neither, individual drugs/extract nor chemo-herbal combinations at tested doses induced any toxicity and damage to organs in nude mice when compared to control group. Toxicological data obtained from this study will help to select the best doses of chemo-herbal combination for future pancreatic xenograft tumor studies.
    Matched MeSH terms: Heterografts
  4. Sultan T, Cheah CW, Ibrahim NB, Asif MK, Vaithilingam RD
    J Dent, 2020 Oct;101:103455.
    PMID: 32828845 DOI: 10.1016/j.jdent.2020.103455
    OBJECTIVES: This clinical study assessed and compared the linear and volumetric changes of extraction sockets grafted with a combination of Platelet-Rich Fibrin (PRF) and Calcium Sulfate (CS) (PRF-CS), and extraction sockets grafted with a combination of PRF and xenograft (X) (PRF-X).

    METHODS: Five single maxillary premolar extraction sockets received PRF-CS grafts and five single maxillary premolar sockets received PRF-X grafts. Linear (horizontal and vertical) measurements were accomplished using Cone Beam Computed Tomography (CBCT) images and volumetric changes were assessed using MIMICS software. Soft tissue level changes were measured using Stonecast models. All measurements were recorded at baseline (before extraction) and at 5-months post-extraction.

    RESULTS: Significant reduction in vertical and horizontal dimensions were observed in both groups except for distal bone height (DBH = 0.44 ± 0.45 mm, p = 0.09) and palatal bone height (PBH = 0.39 ± 0.34 mm, p = 0.06) in PRF-X group. PRF-CS group demonstrated mean horizontal shrinkage of 1.27 ± 0.82 mm (p = 0.02), when compared with PRF-X group (1.40 ± 0.85 mm, p = 0.02). Vertical resorption for mesial bone height (MBH = 0.56 ± 0.25 mm, p = 0.008), buccal bone height (BBH = 1.62 ± 0.91 mm, p = 0.01) and palatal bone height (PBH = 1.39 ± 0.87 mm, p = 0.02) in PRF-CS group was more than resorption in PRF-X group (MBH = 0.28 ± 0.14 mm, p = 0.01, BBH = 0.63 ± 0.39 mm, p = 0.02 and PBH = 0.39 ± 0.34 mm, p = 0.06). Volumetric bone resorption was significant within both groups (PRF-CS = 168.33 ± 63.68 mm3, p = 0.004; PRF-X = 102.88 ± 32.93 mm3, p = 0.002), though not significant (p = 0.08) when compared between groups. In PRF-X group, the distal soft tissue level (DSH = 1.00 ± 0.50 mm, p = 0.03) demonstrated almost 2 times more reduction when compared with PRF-CS group (DSH = 1.00 ± 1.00 mm, 0.08). The reduction of the buccal soft tissue level was pronounced in PRF-CS group (BSH = 2.00 ± 2.00 mm, p = 0.06) when compared with PRF-X group (BSH = 1.00 ± 1.50 mm, p = 0.05).

    CONCLUSIONS: PRF-CS grafted sites showed no significant difference with PRF-X grafted sites in linear and volumetric dimensional changes and might show clinical benefits for socket augmentation. The study is officially registered with ClinicalTrials.gov Registration (NCT03851289).

    Matched MeSH terms: Heterografts
  5. Al Qabbani A, Al Kawas S, A Razak NH, Al Bayatti SW, Enezei HH, Samsudin AR, et al.
    J Craniofac Surg, 2018 Mar;29(2):e203-e209.
    PMID: 29303859 DOI: 10.1097/SCS.0000000000004263
    INTRODUCTION: Alveolar bone is critical in supporting natural teeth, dental implants as well as a removable and fixed prosthesis. Alveolar bone volume diminishes when its associated natural tooth is lost.

    OBJECTIVE: The aim of this study is to evaluate the effectiveness of bovine bone granules on alveolar bone socket augmentation for ridge preservation following atraumatic tooth extraction.

    MATERIALS AND METHODS: Twenty medically fit patients (12 males and 8 females aged between 18 and 40 years) who needed noncomplicated tooth extraction of 1 mandibular premolar tooth were divided randomly and equally into 2 groups. In control group I, the empty extraction socket was left untreated and allowed to heal in a conventional way. In group II, the empty extraction socket wound was filled with lyophilized bovine bone xenograft granules 0.25 to 1 mm of size, 1 mL/vial. A resorbable pericardium membrane was placed to cover the defect. Clinical and 3-dimensional radiological assessments were performed at day 0, 3 months, and 9 months postoperative.

    RESULTS: There were no clinical differences in general wound healing between the groups. Comparisons within the groups showed a significant difference of bone resorption of 1.49 mm (95% confidence interval, 0.63-2.35) at 3 months, and further resorption of 1.84 mm (P ≤ 0.05) at 9 months in the control group. No significant changes of bone resorption were observed in group II during the same time interval. Comparison between groups showed a significant difference of bone resorption at 3 and 9 months (2.40 and 2.88 mm, respectively).

    CONCLUSION: The use of lyophilized demineralized bovine bone granules in socket preservation to fill in the extraction socket seems essential in preserving the alveolar bone dimension as it showed excellent soft and hard tissue healing. This study concludes that the alveolar bone socket exhibited a dynamic process of resorption from the first day of tooth extraction. Evidence shows the possibility of using bovine bone granules routinely in socket volume preservation techniques following tooth extraction.

    Matched MeSH terms: Heterografts
  6. Baharuddin, N.A., Kamin, S., Samsuddin, A.R.
    Ann Dent, 2005;12(1):-.
    MyJurnal
    The aim of this study was to determine the effectiveness of demineralized freeze-dried bone xenograft (DFDBBX) in minimizing post-surgical recession in moderate to advanced adult periodontitis in patients. Nine patients with a total of eighteen intrabony defects were matched for the tooth type, location of defects and periodontal pocket depth (5 to 7mm). Following an initial nonsurgical treatment, recession at defects indicated for surgery was measured pre-operatively. Surgical treatment was carried out by split mouth design, where the test sites were assigned DFDBBX and the control sites were subjected to debridement without the use of DFDBBX. Recessions were measured at 3 months, 6 months and 9 months post-operatively. The results showed no statistically significant difference in mean recession at 3, 6 and 9 months post-operatively compared to baseline for both test and control groups. Thus, DFDBBX was ineffective in minimizing recession on patients with moderate to severe periodontitis, as compared to surgical debridement alone.
    Matched MeSH terms: Heterografts
  7. Baharuddin, N.A., Kamin, S., Samsuddin, A.R.
    Ann Dent, 2003;10(1):-.
    MyJurnal
    This study evaluated the effectiveness of demineralized freeze-dried bone xenograft in reducing post-surgical pocket depth in moderate to advanced adult periodontitis in patients. Nine patients with a total of eighteen intrabony defects were selected for this study. The bony defects were matched for tooth type, location and pocket depth. Following an initial non-surgical treatment, only pockets of 5 to 7 mm deep were indicated for surgery. Periodontal pockets were measured pre-operatively and at 3, 6 and 9 months post-surgically. The study protocol included a split mouth design, where surgical treatment was carried out at both test and control sites. The test sites were assigned demineralized freeze-dried bone xenograft and the control sites were subjected to debridement alone without the use of demineralized freeze-dried bone xenograft. The results from this study showed a statistically significant difference in the mean pocket depth at 6 and 9 months post-operatively for both test and control groups, but there was no statistically significant difference at 3 months. In conclusion, demineralized freeze-dried bone xenograft was ineffective in reducing periodontal pocket depth in patients with moderate to severe periodontitis, as compared to surgical debridement alone.
    Matched MeSH terms: Heterografts
  8. Teoh HK, Chong PP, Abdullah M, Sekawi Z, Tan GC, Leong CF, et al.
    Leuk. Res., 2016 Jan;40:44-53.
    PMID: 26626206 DOI: 10.1016/j.leukres.2015.10.004
    Studies demonstrated that mesenchymal stromal cells (MSC) from bone marrow stroma produced high concentration of interleukin-6 (IL-6) that promoted multiple myeloma cell growth. In view of the failure of IL-6 monoclonal antibody therapy to demonstrate substantial clinical responses in early clinical trials, more effective methods are needed in order to disrupt the favourable microenvironment provided by the bone marrow stroma. In this study, we evaluated the short interfering RNA (siRNA)-mediated silencing of IL-6 in MSC and the efficacy of these genetically modified MSC, with IL-6 suppression, on inhibition of U266 multiple myeloma cell growth. IL-6 mRNA and protein were significantly suppressed by 72h post IL-6 siRNA transfection without affecting the biological properties of MSC. Here we show significant inhibition of cell growth and IL-6 production in U266 cells co-cultured with MSC transfected with IL-6 siRNA when compared to U266 cells co-cultured with control MSC. We also show that the tumour volume and mitotic index of tumours in nude mice co-injected with U266 and MSC transfected with IL-6 siRNA were significantly reduced compared to tumours of mice co-injected with control MSC. Our results suggest potential use of RNA interference mediated therapy for multiple myeloma.
    Matched MeSH terms: Heterografts
  9. Lim WF, Mohamad Yusof MI, Teh LK, Salleh MZ
    Nutrients, 2020 Sep 30;12(10).
    PMID: 33007803 DOI: 10.3390/nu12102993
    Moringa oleifera is a miracle plant with many nutritional and medicinal properties. Chemopreventive values of the combined mixture of moringa leaves and seed residue (MOLSr) at different ratios (M1S9, M1S1 and M9S1) were investigated. MOLSr extracts were subjected to phytochemical screening, antioxidant assays, metabolite profiling and cytotoxic activity on the primary mammary epithelial cells (PMECs), non-malignant Chang's liver cells and various human cancer cell lines (including breast, cervical, colon and liver cancer cell lines). The MOLSr ratio with the most potent cytotoxic activity was used in xenograft mice injected with MDA-MB-231 cells for in vivo tumorigenicity study as well as further protein and gene expression studies. M1S9, specifically composed of saponin and amino acid, retained the lowest antioxidant activity but the highest glucosinolate content as compared to other ratios. Cell viability decreased significantly in MCF-7 breast cancer cells and PMECs after treatment with M1S9. Solid tumor from MDA-MB-231 xenograft mice was inhibited by up to 64.5% at third week after treatment with high-dose M1S9. High-dose M1S9 significantly decreased the expression of calcineurin (CaN) and vascular endothelial cell growth factor (VEGF) proteins as well as the secreted frizzled-related protein 1 (SFRP1) and solute carrier family 39 member 6 (SLC39A6) genes. This study provides new scientific evidence for the chemoprevention potential of MOLSr extracts in a breast cancer model; however, the precise mechanism warrants further investigation.
    Matched MeSH terms: Heterografts
  10. Jiang X, Li Y, Feng JL, Nik Nabil WN, Wu R, Lu Y, et al.
    Front Cell Dev Biol, 2020;8:598620.
    PMID: 33392189 DOI: 10.3389/fcell.2020.598620
    The re-proliferation of quiescent cancer cells is considered to be the primary contributor to prostate cancer (Pca) recurrence and progression. In this study, we investigated the inhibitory effect of safranal, a monoterpene aldehyde isolated from Crocus sativus (saffron), on the re-proliferation of quiescent Pca cells in vitro and in vivo. The results showed that safranal efficiently blocked the re-activation of quiescent Pca cells by downregulating the G0/G1 cell cycle regulatory proteins CDK2, CDK4, CDK6, and phospho-Rb at Ser807/811 and elevating the levels of cyclin-dependent kinase inhibitors, p21 and p27. Further investigation on the underlying mechanisms revealed that safranal suppressed the mRNA and protein expression levels of Skp2, possibly through the deregulation of the transcriptional activity of two major transcriptional factors, E2F1 and NF-κB subunits. Moreover, safranal inhibited AKT phosphorylation at Ser473 and deregulated both canonical and non-canonical NF-κB signaling pathways. Safranal suppressed the tumor growth of quiescent Pca cell xenografts in vivo. Furthermore, safranal-treated tumor tissues exhibited a reduction in Skp2, E2F1, NF-κB p65, p-IκBα (Ser32), c-MYC, p-Rb (Ser807), CDK4, CDK6, and CDK2 and an elevation of p27 and p21 protein levels. Therefore, our findings demonstrate that safranal suppresses cell cycle re-entry of quiescent Pca cells in vitro and in vivo plausibly by repressing the transcriptional activity of two major transcriptional activators of Skp2, namely, E2F1 and NF-κB, through the downregulation of AKT phosphorylation and NF-κB signaling pathways, respectively.
    Matched MeSH terms: Heterografts
  11. Kattimani VS, Prathigudupu RS, Jairaj A, Khader MA, Rajeev K, Khader AA
    J Contemp Dent Pract, 2019 Aug 01;20(8):987-993.
    PMID: 31797859
    Since a long time, the preservation of the socket is emphasized for various reasons. Many studies have suggested the ridge preservation through socket grafting using various bone graft substitute materials (GSMs). But none of the studies suggested the material of choice for the grafting. So, the systematic review was planned to analyze the outcomes of synthetic hydroxyapatite (SHA) graft material for socket preservation. The review was aimed to determine the existing evidence for the use of SHA GSM for grafting and its usefulness.

    MATERIALS AND METHODS: The literature search was performed for the studies published in the English language independently by all four authors (search team) in the Medline database through the PubMed search engine for the past 5 years. The study involved predetermined inclusion and exclusion criteria for the search. The final lists of clinical trials were analyzed to determine the existing evidence and suggested the mechanism of action.

    REVIEW RESULTS: The search resulted in 117 titles. After application of inclusion and exclusion criteria, a total of seven studies were found eligible for this systematic review. Out of seven, two studies were found eligible for meta-analysis whereas remaining included for the systematic review.

    CONCLUSION: The meta-analysis favors socket grafting compared to control in terms of preservation of existing bone height and width. The SHA grafting showed successful bone regeneration with less connective tissue component. The histomorphometric evaluation showed a good bone regeneration associated with SHA than xenograft. Within the limitations of this meta-analysis, the synthetic GSM can be used for socket grafting.

    CLINICAL SIGNIFICANCE: In the wake of increasing graft materials in the market and different origin raw material sources for the preparation of graft materials, clinicians are in dilemma for selection and its use. The success of grafting depends on the selection of appropriate material with a suitable calcium/phosphate (Ca/P) ratio. The review provided available evidence for the use of SHA.

    Matched MeSH terms: Heterografts
  12. Awang-Junaidi AH, Singh J, Honaramooz A
    Reprod Fertil Dev, 2020 Mar;32(6):594-609.
    PMID: 32051087 DOI: 10.1071/RD19043
    Ectopic implantation of donor testis cell aggregates in recipient mice results in de novo formation or regeneration of testis tissue and, as such, provides a unique invivo model for the study of testis development. However, currently the results are inconsistent and the efficiency of the model remains low. This study was designed to: (1) examine several factors that can potentially improve the consistency and efficiency of this model and (2) explore the use of ultrasound biomicroscopy (UBM) for the non-invasive invivo evaluation of implants. Testis cell aggregates, containing ~40% gonocytes, from 1-week-old donor piglets were implanted under the back skin of immunodeficient mice through skin incisions using gel matrices or through subcutaneous injection without using gel matrices. The addition of gel matrices led to inconsistent tissue development; gelatin had the greatest development, followed by collagen, whereas agarose resulted in poor development. The results also depended on the implanted cell numbers since implants with 100×106 cells were larger than those with 50×106 cells. The injection approach for cell implantation was less invasive and resulted in more consistent and efficient testis tissue development. UBM provided promising results as a means of non-invasive monitoring of implants.
    Matched MeSH terms: Heterografts
  13. Mh Busra F, Rajab NF, Tabata Y, Saim AB, B H Idrus R, Chowdhury SR
    J Tissue Eng Regen Med, 2019 05;13(5):874-891.
    PMID: 30811090 DOI: 10.1002/term.2842
    The full-thickness skin wound is a common skin complication affecting millions of people worldwide. Delayed treatment of this condition causes the loss of skin function and integrity that could lead to the development of chronic wounds or even death. This study was aimed to develop a rapid wound treatment modality using ovine tendon collagen type I (OTC-I) bio-scaffold with or without noncultured skin cells. Genipin (GNP) and carbodiimide (EDC) were used to cross-link OTC-I scaffold to improve the mechanical strength of the bio-scaffold. The physicochemical, biomechanical, biodegradation, biocompatibility, and immunogenicity properties of OTC-I scaffolds were investigated. The efficacy of this treatment approach was evaluated in an in vivo skin wound model. The results demonstrated that GNP cross-linked OTC-I scaffold (OTC-I_GNP) had better physicochemical and mechanical properties compared with EDC cross-linked OTC-I scaffold (OTC-I_EDC) and noncross-link OTC-I scaffold (OTC-I_NC). OTC-I_GNP and OTC-I_NC demonstrated no toxic effect on cells as it promoted higher cell attachment and proliferation of both primary human epidermal keratinocytes and human dermal fibroblasts compared with OTC-I_EDC. Both OTC-I_GNP and OTC-I_NC exhibited spontaneous formation of bilayer structure in vitro. Immunogenic evaluation of OTC-I scaffolds, in vitro and in vivo, revealed no sign of immune response. Finally, implantation of OTC-I_NC and OTC-I_GNP scaffolds with noncultured skin cells demonstrated enhanced healing with superior skin maturity and microstructure features, resembling native skin in contrast to other treatment (without noncultured skin cells) and control group. The findings of this study, therefore, suggested that both OTC-I scaffolds with noncultured skin cells could be promising for the rapid treatment of full-thickness skin wound.
    Matched MeSH terms: Heterografts
  14. Kong BH, Teoh KH, Tan NH, Tan CS, Ng ST, Fung SY
    PeerJ, 2020;8:e9650.
    PMID: 32832273 DOI: 10.7717/peerj.9650
    Background: Lignosus tigris, a recently discovered species of the unique Lignosus family, has been traditionally used by the indigenous communities in Peninsular Malaysia to treat various ailments and as an alternative medicine for cancer treatment. The L. tigris cultivar sclerotia (Ligno TG-K) was found to contain numerous bioactive compounds with beneficial biomedicinal properties and the sclerotial extract exhibited potent antioxidant activity. However, the anticancer property of the Ligno TG-K including in vitro and in vivo antitumor effects as well as its anticancer active compounds and the mechanisms has yet to be investigated.

    Methods: The cytotoxicity of the Ligno TG-K against human breast (MCF7), prostate (PC3) and lung (A549) adenocarcinoma cell lines was evaluated using MTT cytotoxicity assay. The cytotoxic mechanisms of the active high molecular weight proteins (HMWp) fraction were investigated through detection of caspases activity and apoptotic-related proteins expression by Western blotting. The in vivo antitumor activity of the isolated HMWp was examined using MCF7 mouse xenograft model. Shotgun LC-MS/MS analysis was performed to identify the proteins in the HMWp.

    Results and Discussion: Cold water extract of the sclerotia inhibited proliferation of MCF7, A549 and PC3 cells with IC50 ranged from 28.9 to 95.0 µg/mL. Bioassay guided fractionation of the extract revealed that HMWp exhibited selective cytotoxicity against MCF7 cells via induction of cellular apoptosis by the activation of extrinsic and intrinsic signaling pathways. HMWp activated expression of caspase-8 and -9 enzymes, and pro-apoptotic Bax protein whilst inhibiting expression of tumor survivor protein, Bcl-2. HMWp induced tumor-cell apoptosis and suppressed growth of tumor in MCF-7 xenograft mice. Lectins, serine proteases, RNase Gf29 and a 230NA deoxyribonuclease are the major cytotoxic proteins that accounted for 55.93% of the HMWp.

    Conclusion: The findings from this study provided scientific evidences to support the traditional use of the L. tigris sclerotia for treatment of breast cancer. Several cytotoxic proteins with high abundance have been identified in the HMWp of the sclerotial extract and these proteins have potential to be developed into new anticancer agents or as adjunct cancer therapy.

    Matched MeSH terms: Heterografts
  15. Lee HM, Lo KW, Wei W, Tsao SW, Chung GTY, Ibrahim MH, et al.
    J Pathol, 2017 05;242(1):62-72.
    PMID: 28240350 DOI: 10.1002/path.4879
    Undifferentiated nasopharyngeal carcinoma (NPC) is a cancer with high metastatic potential that is consistently associated with Epstein-Barr virus (EBV) infection. In this study, we have investigated the functional contribution of sphingosine-1-phosphate (S1P) signalling to the pathogenesis of NPC. We show that EBV infection or ectopic expression of the EBV-encoded latent genes (EBNA1, LMP1, and LMP2A) can up-regulate sphingosine kinase 1 (SPHK1), the key enzyme that produces S1P, in NPC cell lines. Exogenous addition of S1P promotes the migration of NPC cells through the activation of AKT; shRNA knockdown of SPHK1 resulted in a reduction in the levels of activated AKT and inhibition of cell migration. We also show that S1P receptor 3 (S1PR3) mRNA is overexpressed in EBV-positive NPC patient-derived xenografts and a subset of primary NPC tissues, and that knockdown of S1PR3 suppressed the activation of AKT and the S1P-induced migration of NPC cells. Taken together, our data point to a central role for EBV in mediating the oncogenic effects of S1P in NPC and identify S1P signalling as a potential therapeutic target in this disease. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    Matched MeSH terms: Heterografts
  16. Cilwyn-Shalitha B, Sasidharan S
    Microsc Microanal, 2023 Jun 09;29(3):1153-1167.
    PMID: 37749670 DOI: 10.1093/micmic/ozad023
    The present study investigated the effects of Polyalthia longifolia leaf extract against the growth of HeLa cell xenograft tumor in nude mice and its underlying mechanism. The nude mice xenografted with HeLa cells were treated with 5% DMSO (vehicle control), 20 mg/kg/body weight of etoposide (positive control), and 500 and 1000 mg/kg/body weight of leaf extract, respectively. Antitumor activity was evaluated with apoptosis, proliferation, and angiogenesis using microscopic-based histological and immunohistochemical microanalyses. The tumor tissue histological and immunohistochemical analyses showed that the HeLa tumor cell death was associated with apoptosis and decreased (p < 0.05) expression of Ki-67 in tumor tissues. The extract also inhibits tumor angiogenesis by downregulating (p < 0.05) the expression of VEGF and CD31 in tumor tissues after treatment for 35 days. Conclusively, the P. longifolia leaf extract effectively inhibited HeLa cell xenograft growth in nude mice. The possible mechanism was related to induction of apoptosis, inhibition of tumor HeLa cell proliferation by decreasing the Ki-67 protein expression, and prevention of tumor angiogenesis by reducing VEGF and CD31 protein expression in HeLa cells.
    Matched MeSH terms: Heterografts
  17. Hung TH, Li YH, Tseng CP, Lan YW, Hsu SC, Chen YH, et al.
    Cancer Gene Ther, 2015 May;22(5):262-70.
    PMID: 25908454 DOI: 10.1038/cgt.2015.15
    Inappropriate c-MET signaling in cancer can enhance tumor cell proliferation, survival, motility, and invasion. Inhibition of c-MET signaling induces apoptosis in a variety of cancers. It has also been recognized as a novel anticancer therapy approach. Furthermore, reports have also indicated that constitutive expression of P-glycoprotein (ABCB1) is involved in the HGF/c-MET-related pathway of multidrug resistance ABCB1-positive human hepatocellular carcinoma cell lines. We previously reported that elevated expression levels of PKCδ and AP-1 downstream genes, and HGF receptor (c-MET) and ABCB1, in the drug-resistant MES-SA/Dx5 cells. Moreover, leukemia cell lines overexpressing ABCB1 have also been shown to be more resistant to the tyrosine kinase inhibitor imatinib mesylate. These findings suggest that chemoresistant cancer cells may also develop a similar mechanism against chemotherapy agents. To circumvent clinical complications arising from drug resistance during cancer therapy, the present study was designed to investigate apoptosis induction in ABCB1-overexpressed cancer cells using c-MET-targeted RNA interference technology in vitro and in vivo. The results showed that cell viability decreased and apoptosis rate increased in c-MET shRNA-transfected HGF/c-MET pathway-positive MES-SA/Dx5 and MCF-7/ADR2 cell lines in a dose-dependent manner. In vivo reduction of tumor volume in mice harboring c-MET shRNA-knockdown MES-SA/Dx5 cells was clearly demonstrated. Our study demonstrated that downregulation of c-MET by shRNA-induced apoptosis in a multidrug resistance cell line.
    Matched MeSH terms: Heterografts
  18. Sakharkar MK, Dhillon SK, Mazumder M, Yang J
    Genes Cancer, 2021;12:12-24.
    PMID: 33884102 DOI: 10.18632/genesandcancer.210
    Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal type of cancer. In this study, we undertook a pairwise comparison of gene expression pattern between tumor tissue and its matching adjacent normal tissue for 45 PDAC patients and identified 22 upregulated and 32 downregulated genes. PPI network revealed that fibronectin 1 and serpin peptidase inhibitor B5 were the most interconnected upregulated-nodes. Virtual screening identified bleomycin exhibited reasonably strong binding to both proteins. Effect of bleomycin on cell viability was examined against two PDAC cell lines, AsPC-1 and MIA PaCa-2. AsPC-1 did not respond to bleomycin, however, MIA PaCa-2 responded to bleomycin with an IC50 of 2.6 μM. This implicates that bleomycin could be repurposed for the treatment of PDAC, especially in combination with other chemotherapy agents. In vivo mouse xenograft studies and patient clinical trials are warranted to understand the functional mechanism of bleomycin towards PDAC and optimize its therapeutic efficacy. Furthermore, we will evaluate the antitumor activity of the other identified drugs in our future studies.
    Matched MeSH terms: Heterografts
  19. Prodan Z, Mroczek T, Sivalingam S, Bennink G, Asch FM, Cox M, et al.
    PMID: 33984478 DOI: 10.1053/j.semtcvs.2021.03.036
    Valved allografts and xenografts for reconstruction of the right ventricular outflow tract (RVOT) lack durability and do not grow. We report the first clinical use of a completely bioabsorbable valved conduit (Xeltis pulmonary valve - XPV) in children. Twelve children (six male), median age five (two to twelve) years and median weight 17 (10 to 43) kg, underwent RVOT reconstruction with the XPV. Diagnoses were: pulmonary atresia with ventricular septal defect (VSD) (n=4), tetralogy of Fallot (n=4), common arterial trunk (n=3), and transposition of the great arteries with VSD and pulmonary stenosis (n=1). All had had previous surgery, including prior RVOT conduit implantation in six. Two diameters of conduit 16mm (n=5) and 18mm (n=7) were used. At 24 months none of the patients has required surgical re-intervention, 9 of the 12 are in NYHA functional class I and three patients in NYHA class II. None of the conduits has shown evidence of progressive stenosis, dilation or aneurysm formation. Residual peak gradient of >40 mm Hg was observed in three patients, caused by kinking of the conduit at implantation in 1 and distal stenosis in the peripheral pulmonary arteries in 2 patients. Five patients developed severe pulmonary valve insufficiency (PI); the most common mechanism was prolapse of at least one of the valve leaflets. The XPV conduit is a promising innovation for RVOT reconstruction. Progressive PI requires however an improved design (geometry, thickness) of the valve leaflets.
    Matched MeSH terms: Heterografts
  20. Ng MJ, Kong BH, Teoh KH, Yap YH, Ng ST, Tan CS, et al.
    J Ethnopharmacol, 2023 Mar 25;304:115957.
    PMID: 36509254 DOI: 10.1016/j.jep.2022.115957
    ETHNOPHARMACOLOGICAL RELEVANCE: Lignosus rhinocerus (Cooke) Ryvarden (also known as Tiger Milk mushroom, TMM), is a basidiomycete belonging to the Polyporaceae family. It has been documented to be used by traditional Chinese physicians and indigenous people in Southeast Asia to treat a variety of illnesses, such as gastritis, arthritis, and respiratory conditions, as well as to restore patients' physical well-being. TMM has also been used in folk medicine to treat cancer. For example, people from the indigenous Kensiu tribe of northeast Kedah (Malaysia) apply shredded TMM sclerotium mixed with water directly onto breast skin to treat breast cancer, while Chinese practitioners from Hong Kong, China prescribe TMM sclerotium as a treatment for liver cancer. L. rhinocerus has previously been demonstrated to possess selective anti-proliferative properties in vitro, however pre-clinical in vivo research has not yet been conducted.

    AIM OF STUDY: This study aimed to examine the anti-tumor activities of L. rhinocerus TM02®, using two different sample preparations [cold water extract (CWE) and fraction] via various routes of administration (oral and intraperitoneal) on an MCF7-xenograft nude mouse model. This study also investigated the inhibitory effect of TM02® CWE and its fractions against COX-2 in vitro using LPS-induced RAW264.7 macrophages, on the basis of the relationship between COX-2 and metastasis, apoptosis resistance, as well as the proliferation of cancer cells.

    MATERIALS AND METHODS: The first preparation, L. rhinocerus TM02® sclerotium powder (TSP) was dissolved in cold water to obtain the cold water extract (CWE). It was further fractionated based on its molecular weight to obtain the high (HMW), medium (MMW) and low (LMW) molecular weight fractions. The second preparation, known as the TM02® rhinoprolycan fraction (TRF), was obtained by combining the HMW and MMW fractions. TSP was given orally to mimic the daily consumption of a supplement; TRF was administered intraperitoneally to mimic typical tumorous cancer treatment with a rapid and more thorough absorption through the peritoneal cavity. Another experiment was conducted to examine changes in COX-2 activity in LPS-induced RAW264.7 macrophages after a 1-h pre-treatment with CWE, HMW, and MMW.

    RESULTS: Our results revealed that intraperitoneal TRF-injection (90 μg/g BW) for 20 days reduced initial tumor volume by ∼64.3% (n = 5). The percentage of apoptotic cells was marginally higher in TRF-treated mice vs. control, suggesting that induction of apoptosis as one of the factors that led to tumor shrinkage. TSP (500 μg/g BW) oral treatment (n = 5) for 63 days (inclusive of pre-treatment prior to tumor inoculation) effectively inhibited tumor growth. Four of the five tumors totally regressed, demonstrating the effectiveness of TSP ingestion in suppressing tumor growth. Although no significant changes were found in mouse serum cytokines (TNF-α, IL-5, IL-6 and CCL2), some increasing and decreasing trends were observed. This may suggest the immunomodulatory potential of these treatments that can directly or indirectly affect tumor growth. Pre-treatment with CWE, HMW and MMW significantly reduced COX-2 activity in RAW264.7 macrophages upon 24 h LPS-stimulation, suggesting the potential of L. rhinocerus TM02® extract and fractions in regulating M1/M2 polarization.

    CONCLUSION: Based on the findings of our investigation, both the rhinoprolycan fraction and crude sclerotial powder from L. rhinocerus TM02® demonstrated tumor suppressive effects, indicating that they contain substances with strong anticancer potential. The antitumor effects of L. rhinocerus TM02® in our study highlights the potential for further explorations into its mechanism of action and future development as a prophylactic or adjunct therapeutic against tumorous cancer.

    Matched MeSH terms: Heterografts
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