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
AIM: To evaluate the anti-tumour activity and toxicological effects of Orthosiphon stamineus extract formulation (ID: C5EOSEW5050ESA trademarked as Nuva-staticTM), and gemcitabine combination on pancreatic xenograft model.
METHODS: Mice were randomly divided into six groups of 6 mice each (n = 6) and given different treatments for 28 d. The study design consisted of a 2 x 3 factorial treatment structure, with gemcitabine (yes/no) by oral (at 1200 and 400 mg/kg per day). Human pancreatic cancer cells were injected subcutaneously into the flanks of athymic nude mice. C5EOSEW5050ESA (200 or 400 mg/kg per day) was administered orally, while gemcitabine (10 mg/kg per 3 d) was given intraperitoneally either alone or in combination treatment. Histopathological analyses of vital organs, tumour tissues, and incidence of lethality were analysed. Analyses of tumour necrosis and proliferation were determined by haematoxylin-eosin staining and immunohistochemistry for Ki-67, respectively.
RESULTS: No signs of toxicity or damage to vital organs were observed in all treatment groups compared to the untreated group. C5EOSEW5050ESA at 200 mg/kg and gemcitabine combination had no additive antitumor effects compared to a single treatment. Remarkably, a comparably greater response in a reduction in tumour growth, Ki-67 protein expression, and necrosis was demonstrated by 400 mg/kg of C5EOSEW5050ESA and gemcitabine combination than that of the individual agents.
CONCLUSION: These results highlighted the synergistic activity of C5EOSEW5050ESA with gemcitabine to reduce pancreatic tumour growth in mice compared to a single treatment. Thus, this study provides valuable insights into using C5EOSEW5050ESA as a complementary treatment with gemcitabine for pancreatic cancer.
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.
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.
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.
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.
METHODS: The phytochemical and biological criteria of A. zerumbet were in vitro investigated as well as in mouse xenograft model.
RESULTS: A. zerumbet extracts, specially CH2Cl2 and MeOH extracts, exhibited the highest potent anti-tumor activity against Ehrlich ascites carcinoma (EAC) cells. The most active CH2Cl2 extract was subjected to bioassay-guided fractionation leading to isolatation of the naturally occurring 5,6-dehydrokawain (DK) which was characterized by IR, MS, 1H-NMR and 13C-NMR. A. zerumbet extracts, specially MeOH and CH2Cl2 extracts, exhibited significant inhibitory activity towards tumor volume (TV). Furthermore, A. zerumbet extracts declined the high level of malonaldehyde (MDA) as well as elevated the levels of superoxide dismutase (SOD) and catalase (CAT) in liver tissue homogenate. Moreover, DK showed anti-proliferative action on different human cancer cell lines. The recorded IC50 values against breast carcinoma (MCF-7), liver carcinoma (Hep-G2) and larynx carcinoma cells (HEP-2) were 3.08, 6.8, and 8.7 µg/mL, respectively.
CONCLUSION: Taken together, these findings open the door for further investigations in order to explore the potential medicinal properties of A. zerumbet.
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.
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).