Displaying publications 1 - 20 of 28 in total

  1. Baharuddin, N.A., Kamin, S., Samsuddin, A.R.
    Ann Dent, 2005;12(1):-.
    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
  2. Baharuddin, N.A., Kamin, S., Samsuddin, A.R.
    Ann Dent, 2003;10(1):-.
    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
  3. 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
  4. Amin L, Hashim H, Mahadi Z, Che Ngah A, Ismail K
    Xenotransplantation, 2018 11;25(6):e12430.
    PMID: 29932474 DOI: 10.1111/xen.12430
    BACKGROUND: Advances in xenotransplantation have the potential to resolve the issue of organ shortages. Despite this, the procedure is expected to meet with a degree of resistance from the public. The purpose of this study was to identify the relevant factors influencing stakeholders' attitudes towards xenotransplantation.

    METHODS: A multidimensional survey instrument measuring attitudes to xenotransplantation, including the factors that predict such attitudes, was developed based on earlier studies and validated. It was then completed by 469 respondents who were stratified in accordance with stakeholder groups in Malaysia. A single-step SEM analysis was then conducted to estimate the measurement and create a structural model using IBM SPSS Amos version 20 with a maximum-likelihood function.

    RESULTS: The attitudes of Malaysian stakeholders towards xenotransplantation were moderately positive (mean score of 4.20). The most important direct predictor of attitude to xenotransplantation was perceived benefit (β = 0.59, P 

    Matched MeSH terms: Heterografts
  5. Homayoun Hani, Mohd-Azmi Mohd-Lila, Rasedee Abdullah, Zeenathul Nazariah Allaudin, Kazhal Sarsaifi, Faez Firdaus Jesse Abdullah
    Diabetes is one of the major life-threatening health problems worldwide today. It is one of the most fastgrowing diseases that cause many health complications and a leading cause of decreasing life expectancy and high mortality rate. Many studies have suggested several different types of intervention to treat Type 1 diabetes such as insulin therapy, islet transplantation, islet xenotransplantation and stem cell therapy. However, issues regarding the efficacy, cost and safety of these treatments are not always well addressed. For decades, diabetes treatments with few side effects and long-lasting insulin independence has remained one of the most challenging tasks facing scientists. Among the treatments mentioned above, application of human islet transplantation in patients with type 1 diabetes has progressed rapidly with significant achievement. Again, the lack of appropriate donors for islet transplantation and its high cost have led researchers to look for other alternatives. In this review, we discuss very pertinent issues that are related to diabetes treatments, their availability, advantages, disadvantages and also cost,
    Matched MeSH terms: Heterografts
  6. Zhang Y, Lee SH, Wang C, Gao Y, Li J, Xu W
    Jpn J Clin Oncol, 2020 Jun 24.
    PMID: 32579167 DOI: 10.1093/jjco/hyaa089
    BACKGROUND: Patient-derived xenograft model is a powerful and promising tool for drug discovery and cancer biology studies. The application of previous metastatic colorectal cancer models has been greatly limited by its low success rate and long time to develop metastasis. Therefore, in this study, we aim to describe an optimized protocol for faster establishment of colorectal cancer metastatic patient-derived xenograft mouse models.

    METHODS: Smaller micro tissues (˂150 μm in diameter) mixed with Matrigel were engrafted subcutaneously into NSG mice to generate the passage 1 (P1) patient-derived xenograft. The micro tumours from P1 patient-derived xenograft were then excised and orthotopically xenografted into another batch of NSG mice to generate a metastatic colorectal cancer patient-derived xenograft, P2. Haematoxylin and eosin and immunohistochemistry staining were performed to compare the characters between patient-derived xenograft tumours and primary tumours.

    RESULTS: About 16 out of 18 P1 xenograft models successfully grew a tumour for 50.8 ± 5.1 days (success rate 89.9%). Six out of eight P1 xenograft models originating from metastatic patients successfully grew tumours in the colon and metastasized to liver or lung in the NSG recipients for 60.9 ± 4.5 days (success rate 75%). Histological examination of both P1 and P2 xenografts closely resembled the histological architecture of the original patients' tumours. Immunohistochemical analysis revealed similar biomarker expression levels, including CDH17, Ki-67, active β-catenin, Ki-67 and α smooth muscle actin when compared with the original patients' tumours. The stromal components that support the growth of patient-derived xenograft tumours were of murine origin.

    CONCLUSIONS: Metastatic patient-derived xenograft mouse model could be established with shorter time and higher success rate. Although the patient-derived xenograft tumours were supported by the stromal cells of murine origin, they retained the dominant characters of the original patient tumours.

    Matched MeSH terms: Heterografts
  7. Fayaz MA, Awang-Junaidi AH, Singh J, Honaramooz A
    Ultrasound Med Biol, 2020 Nov;46(11):3088-3103.
    PMID: 32800471 DOI: 10.1016/j.ultrasmedbio.2020.07.010
    Testis tissue xenografting and testis cell aggregate implantation from various donor species into recipient mice are novel models for the study and manipulation of testis formation and function in target species. Thus far, the analysis of such studies has been limited to surgical or post-mortem retrieval of samples. Here we used ultrasound biomicroscopy (UBM) to monitor the development of neonatal porcine testis grafts and implants in host mice for 24 wk, and to correlate UBM and (immuno)histologic changes. This led to long-term visualization of gradual changes in volume, dimension and structure of grafts and implants; detection of a 4 wk developmental gap between grafts and implants; and revelation of differences in implant development depending on the craniocaudal site of implantation on the back of host mice. Our data support the reliability and precision of UBM for longitudinal study of transplants, which eliminates the need for frequent surgical sampling.
    Matched MeSH terms: Heterografts
  8. 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
  9. Saad N, Alberio R, Johnson AD, Emes RD, Giles TC, Clarke P, et al.
    Oncotarget, 2018 Mar 23;9(22):16008-16027.
    PMID: 29662623 DOI: 10.18632/oncotarget.24664
    Inducing stable control of tumour growth by tumour reversion is an alternative approach to cancer treatment when eradication of the disease cannot be achieved. The process requires re-establishment of normal control mechanisms that are lost in cancer cells so that abnormal proliferation can be halted. Embryonic environments can reset cellular programmes and we previously showed that axolotl oocyte extracts can reprogram breast cancer cells and reverse their tumorigenicity. In this study, we analysed the gene expression profiles of oocyte extract-treated tumour xenografts to show that tumour reprogramming involves cell cycle arrest and acquisition of a quiescent state. Tumour dormancy is associated with increased P27 expression, restoration of RB function and downregulation of mitogen-activated signalling pathways. We also show that the quiescent state is associated with increased levels of H4K20me3 and decreased H4K20me1, an epigenetic profile leading to chromatin compaction. The epigenetic reprogramming induced by oocyte extracts is required for RB hypophosphorylation and induction of P27 expression, both occurring during exposure to the extracts and stably maintained in reprogrammed tumour xenografts. Therefore, this study demonstrates the value of oocyte molecules for inducing tumour reversion and for the development of new chemoquiescence-based therapies.
    Matched MeSH terms: Heterografts
  10. 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
  11. 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
  12. Zainal NS, Lee BKB, Wong ZW, Chin IS, Yee PS, Gan CP, et al.
    Cancer Biol Med, 2019 May;16(2):264-275.
    PMID: 31516747 DOI: 10.20892/j.issn.2095-3941.2018.0257
    Objective: Lack of effective therapies remains a problem in the treatment of oral squamous cell carcinoma (OSCC), especially in patients with advanced tumors. OSCC development is driven by multiple aberrancies within the cell cycle pathway, including amplification of cyclin D1 and loss of p16. Hence, cell cycle inhibitors of the CDK4/6-cyclin D axis are appealing targets for OSCC treatment. Here, we determined the potency of palbociclib and identified genetic features that are associated with the response of palbociclib in OSCC.

    Methods: The effect of palbociclib was evaluated in a panel of well-characterized OSCC cell lines by cell proliferation assays and further confirmed by in vivo evaluation in xenograft models. PIK3CA-mutant isogenic cell lines were used to investigate the effect of PIK3CA mutation towards palbociclib response.

    Results: We demonstrated that 80% of OSCC cell lines are sensitive to palbociclib at sub-micromolar concentrations. Consistently, palbociclib was effective in controlling tumor growth in mice. We identified that palbociclib-resistant cells harbored mutations in PIK3CA. Using isogenic cell lines, we showed that PIK3CA mutant cells are less responsive to palbociclib as compared to wild-type cells with concurrent upregulation of CDK2 and cyclin E1 protein levels. We further demonstrated that the combination of a PI3K/mTOR inhibitor (PF-04691502) and palbociclib completely controlled tumor growth in mice.

    Conclusions: This study demonstrated the potency of palbociclib in OSCC models and provides a rationale for the inclusion of PIK3CA testing in the clinical evaluation of CDK4/6 inhibitors and suggests combination approaches for further clinical studies.

    Matched MeSH terms: Heterografts
  13. Tan YJ, Lee YT, Petersen SH, Kaur G, Kono K, Tan SC, et al.
    Ther Adv Med Oncol, 2019;11:1758835919878977.
    PMID: 31632470 DOI: 10.1177/1758835919878977
    Background: This study aims to investigate the combination effect of a novel sirtuin inhibitor (BZD9L1) with 5-fluorouracil (5-FU) and to determine its molecular mechanism of action in colorectal cancer (CRC).

    Methods: BZD9L1 and 5-FU either as single treatment or in combination were tested against CRC cells to evaluate synergism in cytotoxicity, senescence and formation of micronucleus, cell cycle and apoptosis, as well as the regulation of related molecular players. The effects of combined treatments at different doses on stress and apoptosis, migration, invasion and cell death mechanism were evaluated through two-dimensional and three-dimensional cultures. In vivo studies include investigation on the combination effects of BZD9L1 and 5-FU on colorectal tumour xenograft growth and an evaluation of tumour proliferation and apoptosis using immunohistochemistry.

    Results: Combination treatments exerted synergistic reduction on cell viability on HCT 116 cells but not on HT-29 cells. Combined treatments reduced survival, induced cell cycle arrest, apoptosis, senescence and micronucleation in HCT 116 cells through modulation of multiple responsible molecular players and apoptosis pathways, with no effect in epithelial mesenchymal transition (EMT). Combination treatments regulated SIRT1 and SIRT2 protein expression levels differently and changed SIRT2 protein localization. Combined treatment reduced growth, migration, invasion and viability of HCT 116 spheroids through apoptosis, when compared with the single treatment. In addition, combined treatment was found to reduce tumour growth in vivo through reduction of tumour proliferation and necrosis compared with the vehicle control group. This highlights the potential therapeutic effects of BZD9L1 and 5-FU towards CRC.

    Conclusion: This study may pave the way for use of BZD9L1 as an adjuvant to 5-FU in improving the therapeutic efficacy for the treatment of colorectal cancer.

    Matched MeSH terms: Heterografts
  14. 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
  15. Zakaria N, Mohd KS, Ahmed Saeed MA, Ahmed Hassan LE, Shafaei A, Al-Suede FSR, et al.
    Asian Pac J Cancer Prev, 2020 Apr 01;21(4):943-951.
    PMID: 32334454 DOI: 10.31557/APJCP.2020.21.4.943
    BACKGROUND: Uterine fibroids are a common type of solid tumor presenting in women of reproductive age. There are very few alternative treatment available from conventional treatment involving surgeries. Labisia pumila var. alata or locally known as 'Kacip Fatimah' was widely used as traditional medicine in Malaysia. This plant has been used to maintain a healthy female reproductive system. The present study aimed to evaluate anti fibroid potential of L. pumila extracts through in vitro apoptosis activity against uterine leiomyoma cells (SK-UT-1) and in uterine leiomyoma xenograft model. Evaluation of bioactive markers content were also carried out.

    METHODS: Apoptotic induction of the extracts was determined by morphological examination of AO/PI dual staining assay by flourescent microscopy and flow cytometry analysis on Annexin V-FITC/PI stained cells. In vivo study was done in immune-compromised mouse xenograft model. HPLC analysis was employed to quantify marker compounds.

    RESULTS: Morphological analysis showed L. pumila induced apoptosis in a dose dependent manner against SK-UT-1 cells. In vivo study indicated that L. pumila significantly suppressed the growth of uterine fibroid tumor. All tested extracts contain bioactive marker of gallic acid and cafeic acid.

    CONCLUSION: This work provide significant data of the potential of L. pumila in management of uterine fibroids.

    Matched MeSH terms: Heterografts
  16. 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
  17. 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
  18. 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
  19. 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
  20. 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
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