Displaying publications 1 - 20 of 23 in total

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  1. 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: Transplantation, Heterologous*
  2. 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: Transplantation, Heterologous
  3. 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: Transplantation, Heterologous
  4. Vakhshiteh F, Allaudin ZN, Mohd Lila MA, Hani H
    Xenotransplantation, 2013 02 14;20(2):82-8.
    PMID: 23406308 DOI: 10.1111/xen.12023
    BACKGROUND: The successful isolation, purification, and culture of caprine islets has recently been reported. The present study shows arange of size distribution in caprine islet diameter from 50 to 250 μm, in which 80% of the total islet yield was comprised of small islets.

    METHODS: Caprine islets were isolated and purified. Islets were handpicked and the diameter of the islets was recorded using light microscopy. Viablility of the islets was analyzed by confocal microscopy. Insulin secretion assay was carried out and analyzed by ELISA.

    RESULTS: When tested at 48 h after isolation, these small islets were 29.3% more viable compared to the large-sized islets. Large islets showed a high ratio (P 

    Matched MeSH terms: Transplantation, Heterologous*
  5. 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: Transplantation, Heterologous
  6. Homayoun Hani, Mohd-Azmi Mohd-Lila, Rasedee Abdullah, Zeenathul Nazariah Allaudin, Kazhal Sarsaifi, Faez Firdaus Jesse Abdullah
    MyJurnal
    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: Transplantation, Heterologous
  7. Hani H, Allaudin ZN, Mohd-Lila MA, Ibrahim TA, Othman AM
    Xenotransplantation, 2014 Mar-Apr;21(2):174-82.
    PMID: 24645790 DOI: 10.1111/xen.12087
    BACKGROUND: Type 1 diabetes mellitus is a devastating disease for which there is currently no cure, but only lifetime management. Islet xenotransplantation is a promising technique for the restoration of blood glucose control in patients with diabetes mellitus. The purpose of this study was to explore the potential use of caprine (goat) islet cells as xenogeneic grafts in the treatment for diabetes in a mouse model.
    METHODS: Caprine pancreases were harvested and transported to the laboratory under conditions optimized to prevent ischemia. Islets were isolated, purified, and tested for functionality. Caprine islets (2000 islet equivalent) were transplanted beneath the kidney capsules of diabetic BALB/c mice under thalidomide-induced immunosuppression. Blood glucose and insulin levels of grafted mice were evaluated by glucometer and enzyme-linked immunosorbent assay kit, respectively. The functionality and quality of caprine pancreatic islet grafts were assessed by intraperitoneal glucose tolerance tests.
    RESULTS: The viability of purified islet cells exceeded 90%. Recipient mice exhibited normoglycemia (<11 mM glucose) for 30 days. In addition, weight gain negatively correlated with blood glucose level. The findings verified diabetes reversal in caprine islet recipient mice. A significant drop in non-fasting blood glucose level (from 23.3 ± 5.4 to 8.04 ± 0.44 mM) and simultaneous increase in serum insulin level (from 0.01 ± 0.001 to 0.56 ± 0.17 μg/l) and body weights (from 23.64 ± 0.31 to 25.85 ± 0.34 g) were observed (P < 0.05). Immunohistochemical analysis verified insulin production in the transplanted islets.
    CONCLUSIONS: Purified caprine islets were demonstrated to successfully sustain viability and functionality for controlling blood glucose levels in an immunosuppressed mouse model of diabetes. These results suggest the use of caprine islets as an addition to the supply of xenogeneic islets for diabetes research.
    KEYWORDS: caprine islets; streptozotocin‐injected mice; type 1 diabetes; xenotransplantation
    Matched MeSH terms: Transplantation, Heterologous*
  8. Koay AC, Yew YH, Ngo CT, Loo VP, Intan G, Chua CN
    Med J Malaysia, 2008 Dec;63(5):421-2.
    PMID: 19803308 MyJurnal
    Corneal perforation is an ocular emergency that requires early intervention to avoid permanent visual loss from endophthalmitis or irreversible structural changes. Although tectonic keratoplasty is the best choice for patching a large perforation, a donor cornea is not always immediately available. Consequently, an alternative material is required while awaiting a donor cornea. We report the use of preserved bovine pericardium as a temporizing graft to maintain the ocular integrity in two patients with corneal perforation.
    Matched MeSH terms: Transplantation, Heterologous/methods*
  9. Baharuddin A, Go BT, Firdaus MN, Abdullah J
    Clin Neurol Neurosurg, 2002 Sep;104(4):342-4.
    PMID: 12140102
    Bovine pericardium has widely been used for grafts in cardiac surgery and seems to have suitable properties for use as a dural graft. We report our experience of using locally processed bovine pericardium for dural grafts in 22 patients undergoing cranial operations.
    Matched MeSH terms: Transplantation, Heterologous*
  10. Hoe SLL, Tan LP, Abdul Aziz N, Liew K, Teow SY, Abdul Razak FR, et al.
    Sci Rep, 2017 09 28;7(1):12372.
    PMID: 28959019 DOI: 10.1038/s41598-017-12045-8
    Subpopulations of nasopharyngeal carcinoma (NPC) contain cells with differential tumourigenic properties. Our study evaluates the tumourigenic potential of CD24, CD44, EpCAM and combination of EpCAM/CD44 cells in NPC. CD44br and EpCAMbr cells enriched for higher S-phase cell content, faster-growing tumourigenic cells leading to tumours with larger volume and higher mitotic figures. Although CD44br and EpCAMbr cells significantly enriched for tumour-initiating cells (TICs), all cells could retain self-renewal property for at least four generations. Compared to CD44 marker alone, EpCAM/CD44dbr marker did not enhance for cells with faster-growing ability or higher TIC frequency. Cells expressing high CD44 or EpCAM had lower KLF4 and p21 in NPC subpopulations. KLF4-overexpressed EpCAMbr cells had slower growth while Kenpaullone inhibition of KLF4 transcription increased in vitro cell proliferation. Compared to non-NPC, NPC specimens had increased expression of EPCAM, of which tumours from advanced stage of NPC had higher expression. Together, our study provides evidence that EpCAM is a potentially important marker in NPC.
    Matched MeSH terms: Transplantation, Heterologous*
  11. Abdullah J, Rushdan A, Hamzah M, Ariff AR, Rani A
    Ann. Transplant., 1999;4(3-4):28-31.
    PMID: 10853777
    Four patients underwent reconstruction of anterior cranial fossa of skull defects between November 1997 and January 1998. All of them had traumatic anterior cranial fossa defect and were reconstructed with lyophilised bovine cortical bone graft. There was no cerebrospinal fluid leakage, meningitis, extradural abscess or other infections. This study demonstrates that the use of bovine bone graft in the reconstruction of anterior base defects is safe.
    Matched MeSH terms: Transplantation, Heterologous
  12. Azhim A, Syazwani N, Morimoto Y, Furukawa KS, Ushida T
    J Biomater Appl, 2014 Jul;29(1):130-41.
    PMID: 24384523 DOI: 10.1177/0885328213517579
    A novel decellularization method using sonication treatment is described. Sonication treatment is the combination of physical and chemical agents. These methods will disrupt cell membrane and release cell contents to external environments. The cell removal was facilitated by subsequent rinsing of sodium dodecyl sulfate detergents. Sonication treatment is used in the preparation of complete decellularized bioscaffolds. The aim of this study is to confirm the usefulness of sonication treatment for preparation of biological scaffolds. In this study, samples of aortic tissues are decellularized by sonication treatment at frequency of 170 kHz in 0.1% and 2% sodium dodecyl sulfate detergents for 10-h treatment time. The relation between decellularization and sonication parameters such as dissolved oxygen concentration, conductivity, and pH is investigated. Histological analysis and biomechanical testing is performed to evaluate cell removal efficiency as well as changes in biomechanical properties. Minimal inflammation response elicit by bioscaffolds is confirmed by xenogeneic implantation and immunohistochemistry. Sonication treatment is able to produce complete decellularized tissue suggesting that these treatments could be applied widely as one of the decellularization method.
    Matched MeSH terms: Transplantation, Heterologous
  13. Hani H, Ibrahim TA, Othman AM, Lila MA, bt Allaudin ZN
    Xenotransplantation, 2010 12 17;17(6):469-80.
    PMID: 21158948 DOI: 10.1111/j.1399-3089.2010.00616.x
    BACKGROUND: Insufficient availability of human donors makes the search for alternative source of islet cells mandatory for future developments in pancreatic transplantation. The present study investigates the potential of caprine as an alternative source of pancreatic islets. The objectives of the study were to optimize techniques for caprine islet isolation and purification for culture establishment, and to subsequently assess their viable and functional potential.

    METHODS: Caprine pancreatic tissues were collected from a local slaughterhouse and prior transported to the laboratory by maintaining the cold chain. Islets were obtained by a collagenase-based digestion and optimized isolation technique. Islet cell purity and viability were determined by dithizone and trypan blue staining, respectively. Islet clusters of different sizes were positively identified by staining methods and demonstrated 90% viability in the culture system. Following static incubation, an in vitro insulin secretion assay was carried out and analyzed by ELISA.

    RESULTS: The islets remained satisfactorily viable for 5 days in the culture system following regular media changes. The current study has successfully optimized the isolation, purification and culture maintenance of caprine islets.

    CONCLUSION: The successful yield, viability and functionality of islets isolated from the optimized protocol provide promising potential as an alternative source of islets for diabetes and transplantation researches.

    Matched MeSH terms: Transplantation, Heterologous
  14. Fåhraeus R, Fu HL, Ernberg I, Finke J, Rowe M, Klein G, et al.
    Int J Cancer, 1988 Sep 15;42(3):329-38.
    PMID: 2843473
    Expression of the Epstein-Barr virus (EBV) encoded nuclear antigens (EBNA 1 to 6) and membrane-associated protein (LMP) was investigated by immunoblotting in 83 nasopharyngeal carcinoma (NPC) biopsies and 25 other tumor and normal tissue specimens from the head and neck region. Fifty-eight of the 83 NPC biopsies were large enough to yield parallel data on virus DNA and viral expression. All 16 cases of clinically diagnosed and histologically confirmed NPCs from North Africa contained EBV DNA and expressed EBNA-1. Of 31 clinically diagnosed NPCs from China, 29 contained EBV DNA and 25 of these expressed EBNA-1. One control tissue biopsy from the oropharynx of NPC patients contained EBV DNA, but none expressed EBNA-1. The latent membrane protein (LMP) was detected in 22/31 of the Chinese and in 10/16 of the North African NPC biopsies. None of the NPC biopsies or control tissues expressed detectable amounts of EBNA 2 or any of the other 4 nuclear antigens which are invariably expressed in EBV-transformed B cells. A smaller number of tumors from Malaysia and East Africa exhibited a similar pattern of expression. EBV was rescued from a nude-mouse-passaged North African NPC tumor by co-cultivation of the tumor cells with umbilical cord blood lymphocytes. The tumor expressed EBNA 1 and LMP, but not EBNA 2 or the other 4 EBNAs. The resulting LCLs expressed all 6 nuclear antigens, EBNA 1 to 6 and LMP. Our data suggest that expression of the EBV genome is regulated in a tissue-specific fashion.
    Matched MeSH terms: Transplantation, Heterologous
  15. Teow SY, Liew K, Che Mat MF, Marzuki M, Abdul Aziz N, Chu TL, et al.
    BMC Biotechnol, 2019 06 14;19(1):34.
    PMID: 31200673 DOI: 10.1186/s12896-019-0528-4
    BACKGROUND: In vitro modelling of cancer cells is becoming more complex due to prevailing evidence of intimate interactions between cancer cells and their surrounding stroma. A co-culture system which consists of more than one cell type is physiologically more relevant and thus, could serve as a useful model for various biological studies. An assay that specifically detects the phenotypic changes of cancer cells in a multi-cellular system is lacking for nasopharyngeal carcinoma (NPC).

    RESULTS: Here, we describe a luciferase/luciferin (XenoLuc) assay that could specifically measure changes in the proliferation of cancer cells in the co-culture system using two modified NPC patient-derived tumour xenograft (PDTXs) cells: Xeno284-gfp-luc2 and XenoB110-gfp-luc2. Through this assay, we are able to show that the growth of NPC xenograft cells in both two-dimensional (2D) and three-dimensional (3D) models was enhanced when co-cultured with normal human dermal fibroblasts (NHDFs). In addition, potential applications of this assay in in vitro drug or inhibitor screening experiments are also illustrated.

    CONCLUSIONS: XenoLuc assay is specific, sensitive, rapid and cost-effective for measuring the growth of luciferase-expressing cells in a co- or multiple-culture system. This assay may also be adapted for tumour microenvironment studies as well as drug screening experiments in more complex 3D co-culture systems.

    Matched MeSH terms: Transplantation, Heterologous
  16. Khanna RK, Mokhtar E
    Indian J Ophthalmol, 2008 8 20;56(5):429-30.
    PMID: 18711278
    To describe use of a locally processed bovine pericardium (BP) to cover a large central corneal perforation following alkali injury and discuss postoperative outcome. A 27-year-old Malay male patient presented two weeks after alkali splashed in his left eye while working. A clinical diagnosis of left central corneal ulcer with limbal ischemia following alkali injury with secondary infection was made. After failed medical therapy, we performed a Gunderson conjunctival flap under local anesthesia that retracted after one week and resulted in a large central corneal perforation with surrounding stromal thinning. The perforation was covered with a locally processed BP xenograft (Lyolemb) supplied by the National Tissue Bank, University Sains Malaysia. Nine months follow-up showed a well-taken graft without any exposure/dehiscence and minimal inflammation. Amniotic membrane transplantation when used as a patch graft needs an urgent tectonic graft to promote corneal stability in patients with severe corneal thinning. The use of processed BP can be a viable option in treating such cases.
    Matched MeSH terms: Transplantation, Heterologous
  17. Leow SN, Luu CD, Hairul Nizam MH, Mok PL, Ruhaslizan R, Wong HS, et al.
    PLoS One, 2015;10(6):e0128973.
    PMID: 26107378 DOI: 10.1371/journal.pone.0128973
    To investigate the safety and efficacy of subretinal injection of human Wharton's Jelly-derived mesenchymal stem cells (hWJ-MSCs) on retinal structure and function in Royal College of Surgeons (RCS) rats.
    Matched MeSH terms: Transplantation, Heterologous
  18. Hani H, Allaudin ZN, Tengku Ibrahim TA, Mohd-Lila MA, Sarsaifi K, Camalxaman SN, et al.
    In Vitro Cell Dev Biol Anim, 2015 Feb;51(2):113-20.
    PMID: 25303943 DOI: 10.1007/s11626-014-9821-7
    Pancreatic islet transplantation is commonly used to treat diabetes. Cell isolation and purification methods can affect the structure and function of the isolated islet cells. Thus, the development of cell isolation techniques that preserve the structure and function of pancreatic islet cells is essential for enabling successful transplantation procedures. The impact of purification procedures on cell function can be assessed by performing ultrastructure and in vivo studies. Thus, the aim of this study was to evaluate the effect of caprine islets purification procedure on islet cell ultrastructure and functional integrity prior to and post-isolation/purification. The islets were isolated from caprine pancreas by using an optimized collagenase XI-S concentration, and the cells were subsequently purified using Euro-Ficoll density gradient. In vitro viability of islets was determined by fluorescein diacetate and propidium iodide staining. Static incubation was used to assess functionality and insulin production by islet cells in culture media when exposed to various levels of glucose. Pancreatic tissues were examined by using light microscopy, fluorescence microscopy, scanning, and transmission electron microscopy. In vivo viability and functionality of caprine islets were assessed by evaluating the transplanted islets in diabetic mice. Insulin assay of glucose-stimulated insulin secretion test showed that the insulin levels increased with increasing concentration of glucose. Thus, purified islets stimulated with high glucose concentration (25 mM) secreted higher levels of insulin (0.542 ± 0.346 μg/L) than the insulin levels (0.361 ± 0.219, 0.303 ± 0.234 μg/L) secreted by exposure to low glucose concentrations (1.67 mM). Furthermore, insulin levels of recipient mice were significantly higher (p 
    Matched MeSH terms: Transplantation, Heterologous
  19. Kamarul T, Krishnamurithy G, Salih ND, Ibrahim NS, Raghavendran HR, Suhaeb AR, et al.
    ScientificWorldJournal, 2014;2014:905103.
    PMID: 25298970 DOI: 10.1155/2014/905103
    The in vivo biocompatibility and toxicity of PVA/NOCC scaffold were tested by comparing them with those of a biocompatible inert material HAM in a rat model. On Day 5, changes in the blood parameters of the PVA/NOCC-implanted rats were significantly higher than those of the control. The levels of potassium, creatinine, total protein, A/G, hemoglobulin, erythrocytes, WBC, and platelets were not significantly altered in the HAM-implanted rats, when compared with those in the control. On Day 10, an increase in potassium, urea, and GGT levels and a decrease in ALP, platelet, and eosinophil levels were noted in the PVA/NOCC-implanted rats, when compared with control. These changes were almost similar to those noted in the HAM-implanted rats, except for the unaltered potassium and increased neutrophil levels. On Day 15, the total protein, A/G, lymphocyte, monocyte, and eosinophil levels remained unaltered in the PVA/NOCC-implanted rats, whereas urea, A/G, WBC, lymphocyte, and monocyte levels remained unchanged in the HAM-implanted rats. Histology and immunohistochemistry analyses revealed inflammatory infiltration in the PVA/NOCC-implanted rats, but not in the HAM-implanted rats. Although a low toxic tissue response was observed in the PVA/NOCC-implanted rats, further studies are necessary to justify the use of this material in tissue engineering applications.
    Matched MeSH terms: Transplantation, Heterologous
  20. Stebbing J, Zhang H, Xu Y, Lit LC, Green AR, Grothey A, et al.
    Oncogene, 2015 Apr 16;34(16):2103-14.
    PMID: 24909178 DOI: 10.1038/onc.2014.129
    Kinase suppressor of Ras-1 (KSR1) facilitates signal transduction in Ras-dependent cancers, including pancreatic and lung carcinomas but its role in breast cancer has not been well studied. Here, we demonstrate for the first time it functions as a tumor suppressor in breast cancer in contrast to data in other tumors. Breast cancer patients (n>1000) with high KSR1 showed better disease-free and overall survival, results also supported by Oncomine analyses, microarray data (n=2878) and genomic data from paired tumor and cell-free DNA samples revealing loss of heterozygosity. KSR1 expression is associated with high breast cancer 1, early onset (BRCA1), high BRCA1-associated ring domain 1 (BARD1) and checkpoint kinase 1 (Chk1) levels. Phospho-profiling of major components of the canonical Ras-RAF-mitogen-activated protein kinases pathway showed no significant changes after KSR1 overexpression or silencing. Moreover, KSR1 stably transfected cells formed fewer and smaller size colonies compared to the parental ones, while in vivo mouse model also demonstrated that the growth of xenograft tumors overexpressing KSR1 was inhibited. The tumor suppressive action of KSR1 is BRCA1 dependent shown by 3D-matrigel and soft agar assays. KSR1 stabilizes BRCA1 protein levels by reducing BRCA1 ubiquitination through increasing BARD1 abundance. These data link these proteins in a continuum with clinical relevance and position KSR1 in the major oncoprotein pathways in breast tumorigenesis.
    Matched MeSH terms: Transplantation, Heterologous
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