Displaying publications 841 - 860 of 1526 in total

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  1. Sulong NA, Latif MT, Sahani M, Khan MF, Fadzil MF, Tahir NM, et al.
    Chemosphere, 2019 Mar;219:1-14.
    PMID: 30528968 DOI: 10.1016/j.chemosphere.2018.11.195
    This study aimed to determine the distribution and potential health risks of polycyclic aromatic hydrocarbons (PAHs) in PM2.5 collected in Kuala Lumpur during different monsoon seasons. The potential sources of PM2.5 were investigated using 16 priority PAHs with additional of biomass tracers namely levoglucosan (LV), mannosan (MN) and galactosan (GL). This study also investigated the cytotoxic potential of the extracted PAHs towards V79-4 cells. A high-volume air sampler (HVS) was used to collect PM2.5 samples for 24 h. PAHs were extracted using dichloromethane (DCM) while biomass tracers were extracted by a mixture of DCM/methanol (3:1) before analysis with gas chromatography-mass spectrometry (GC-MS). The cytotoxicity of the PAHs extract was determined by assessing the cell viability through the reduction of tetrazolium salts (MTT). The results showed that the total mean ± SD concentrations of PAHs during the southwest (SW) and northeast (NE) monsoons were 2.51 ± 0.93 ng m-3 and 1.37 ± 0.09 ng m-3, respectively. Positive matrix factorization (PMF) using PAH and biomass tracer concentrations suggested four potential sources of PM2.5; gasoline emissions (29.1%), natural gas and coal burning (28.3%), biomass burning (22.3%), and diesel and heavy oil combustion (20.3%). Health risk assessment showed insignificant incremental lifetime cancer risk (ILCR) of 2.40E-07 for 70 years of exposure. MTT assay suggested that PAHs extracts collected during SW monsoon have cytotoxic effect towards V79-4 cell at the concentrations of 25 μg mL-1, 50 μg mL-1, 100 μg mL-1 whereas non-cytotoxic effect was observed on the PAHs sample collected during NE monsoon.
    Matched MeSH terms: Cell Survival
  2. Tang IP, Ngui LX, Ramachandran K, Lim LY, Voon PJ, Yu KL, et al.
    Eur Arch Otorhinolaryngol, 2019 Sep;276(9):2475-2482.
    PMID: 31227870 DOI: 10.1007/s00405-019-05522-5
    PURPOSE: To study the surgical and oncological outcomes of endoscopic endonasal transpterygoid nasopharyngectomy (EETN) in salvaging locally recurrent nasopharyngeal carcinoma (NPC).

    METHOD: This was a retrospective clinical record review study carried out at a tertiary centre from June 2013 until May 2017. A total of 55 locally recurrent NPC patients (rT1-rT4) underwent EETN performed by single skull base surgeon with curative intention with postoperative adjuvant chemotherapy but without postoperative radiotherapy.

    RESULTS: There were 44 (80.0%) males and 11 (20.0%) females, with mean age of 52.5 years. The mean operating time was 180 min (range 150-280 min). 85% (47/55) of patients achieved en bloc tumour resection. 93% (51/55) of patients obtained negative microscopic margin based on postoperative histopathological evaluation. Intraoperatively, one (1.8%) patient had internal carotid artery injury which was successfully stented and had recovered fully without neurological deficit. There were no major postoperative complications reported. During a mean follow-up period of 18-month (range 12-48 months) postsurgery, five patients (9.1%) had residual or recurrence at the primary site. All five patients underwent re-surgery. One patient at rT3 passed away 6 months after re-surgery due to distant metastasis complicated with septicaemia. The 1-year local disease-free rate was 93% and the 1-year overall survival rate was 98%.

    CONCLUSIONS: EETN is emerging treatment options for locally recurrent NPC, with relatively low morbidity and encouraging short-term outcome. Long-term outcome is yet to be determined with longer follow-up and bigger cohort study. However, a successful surgical outcome required a very experienced team and highly specialised equipment.

    Matched MeSH terms: Survival Rate
  3. Al Hariri YK, Sulaiman SAS, Khan AH, Adnan AS, Al Ebrahem SQ
    J Infect Public Health, 2019 07 04;12(6):751-759.
    PMID: 31281106 DOI: 10.1016/j.jiph.2019.06.014
    Leptospirosis is the most widely spread zoonosis and Leptospirosis Associated Acute Kidney Injury (LAKI) is common and fatal if not properly and swiftly treated. The aim of this review is to evaluate the mortality of LAKI and to identify the risk factors for its development. An electronic search was performed to identify the studies included LAKI patients series. Only studies which investigated mortality or risk factors for LAKI development in adults were included. Twenty-three studies with 24 patients series were included in the final analysis and included 1698 patients. The median series mortality was 10.05% (range 0-33.3%) with a total of 223 death. Only four studies identified the independent risk factors for LAKI development which were oliguria, jaundice, arrhythmia, crackles, elevated direct bilirubin level, elevated activated prothrombin time, hyperbilirubinemia and leukocytosis. Although the mortality of LAKI is high, its predictors are not studied enough in literature.
    Matched MeSH terms: Survival Analysis
  4. Ghani WMN, Ramanathan A, Prime SS, Yang YH, Razak IA, Abdul Rahman ZA, et al.
    Cancer Invest, 2019;37(7):275-287.
    PMID: 31307249 DOI: 10.1080/07357907.2019.1635614
    Previous studies found that ethnicity influences oral cancer patients' survival; however, most studies were limited to certain ethnic groups particularly from the West, thus of limited relevance to Asians where the disease is most prevalent. We investigated the relationship between ethnicity and patient survival in multi-racial Malaysia. 5-year survival rate was 40.9%. No statistically significant difference was observed in survival between Malays, Chinese, Indians and Indigenous peoples (45.7%, 44.0%, 41.3%, 27.7% respectively). Increased tumor size, lymph node involvement and advanced tumor were predictive of poor survival. We conclude that ethnicity has no effect on survival or its prognostic indicators.
    Matched MeSH terms: Survival Rate
  5. Ahn J, Lim J, Jusoh N, Lee J, Park TE, Kim Y, et al.
    PMID: 31380359 DOI: 10.3389/fbioe.2019.00168
    Bone is one of the most common sites of cancer metastasis, as its fertile microenvironment attracts tumor cells. The unique mechanical properties of bone extracellular matrix (ECM), mainly composed of hydroxyapatite (HA) affect a number of cellular responses in the tumor microenvironment (TME) such as proliferation, migration, viability, and morphology, as well as angiogenic activity, which is related to bone metastasis. In this study, we engineered a bone-mimetic microenvironment to investigate the interactions between the TME and HA using a microfluidic platform designed for culturing tumor cells in 3D bone-mimetic composite of HA and fibrin. We developed a bone metastasis TME model from colorectal cancer (SW620) and gastric cancer (MKN74) cells, which has very poor prognosis but rarely been investigated. The microfluidic platform enabled straightforward formation of 3D TME composed the hydrogel and multiple cell types. This facilitated monitoring of the effect of HA concentration and culture time on the TME. In 3D bone mimicking culture, we found that HA rich microenvironment affects cell viability, proliferation and cancer cell cytoplasmic volume in a manner dependent on the different metastatic cancer cell types and culture duration indicating the spatial heterogeneity (different origin of metastatic cancer) and temporal heterogeneity (growth time of cancer) of TME. We also found that both SW620 and MKN72 cells exhibited significantly reduced migration at higher HA concentration in our platform indicating inhibitory effect of HA in both cancer cells migration. Next, we quantitatively analyzed angiogenic sprouts induced by paracrine factors that secreted by TME and showed paracrine signals from tumor and stromal cell with a high HA concentration resulted in the formation of fewer sprouts. Finally we reconstituted vascularized TME allowing direct interaction between angiogenic sprouts and tumor-stroma microspheroids in a bone-mimicking microenvironment composing a tunable HA/fibrin composite. Our multifarious approach could be applied to drug screening and mechanistic studies of the metastasis, growth, and progression of bone tumors.
    Matched MeSH terms: Cell Survival
  6. Paul M, Asmi NH, Omar EK, Abdullah S, Mohamad I
    Oman Med J, 2019 Jan;34(1):74-77.
    PMID: 30671189 DOI: 10.5001/omj.2019.13
    Mantle cell lymphoma (MCL) is a rare, aggressive subtype of non-Hodgkin lymphoma with a poor prognosis and high recurrence rate. It seldom affects the Waldeyer's ring let alone the nasopharynx. Patients usually present at late stages of the disease leading to poor failure-free and overall survival rates. Intensive chemotherapy regimes and autologous stem cell transplantation have reported increased survival rates. We report a relapsed case of nasopharyngeal MCL, which previously occurred in the gastrointestinal tract. The patient had undergone a hemicolectomy for colon intussusception secondary to the intraluminal lymphoma mass. He was unable to complete the treatment regime for MCL due to the adverse side effects. Oropharyngeal mass was discovered during routine outpatient follow-up, which was confirmed as nasopharyngeal MCL. We discuss the prognosis, disease progression, and possible treatments.
    Matched MeSH terms: Survival Rate
  7. Zakaria Z, Zulkifle MF, Wan Hasan WAN, Azhari AK, Abdul Raub SH, Eswaran J, et al.
    Onco Targets Ther, 2019;12:7749-7756.
    PMID: 31571924 DOI: 10.2147/OTT.S214611
    Background: Epidermal growth factor receptor (EGFR) is a member of the ErbB family of tyrosine kinase receptor proteins that plays important roles in tumour cell survival and proliferation. EGFR has been reported to be overexpressed in up to 78% of triple-negative breast cancer (TNBC) cases suggesting it as a potential therapeutic target. The clinical trials of anti-EGFR agents in breast cancer showed low response rates. However, a subgroup of patients demonstrated response to EGFR inhibitors highlighting the necessity to stratify patients, who might benefit from effective combination therapy that could include anti EGFR-agents. Population variability in EGFR expression warrants systematic evaluation in specific populations.

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

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

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

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

    Matched MeSH terms: Cell Survival
  8. Mohd Sazlly Lim S, Zainal Abidin A, Liew SM, Roberts JA, Sime FB
    J Infect, 2019 12;79(6):593-600.
    PMID: 31580871 DOI: 10.1016/j.jinf.2019.09.012
    OBJECTIVE: The objective of this works was to assess the global prevalence of multidrug-resistance among A. baumannii causing hospital-acquired (HAP) and ventilator-associated pneumonia (VAP), and describe its associated mortality.

    METHODS: We performed a systematic search of four databases for relevant studies. Meta-analysis was done based on United Nations geoscheme regions, individual countries and study period. We used a random-effects model to calculate pooled prevalence and mortality estimates with 95% confidence intervals (CIs), weighted by study size.

    RESULTS: Among 6445 reports screened, we identified 126 relevant studies, comprising data from 29 countries. The overall prevalence of multidrug-resistance among A. baumannii causing HAP and VAP pooled from 114 studies was 79.9% (95% CI 73.9-85.4%). Central America (100%) and Latin America and the Caribbean (100%) had the highest prevalence, whereas Eastern Asia had the lowest (64.6%; 95% CI, 50.2-77.6%). The overall mortality estimate pooled from 27 studies was 42.6% (95% CI, 37.2-48.1%).

    CONCLUSIONS: We observed large amounts of variation in the prevalence of multidrug-resistance among A. baumannii causing HAP and VAP and its mortality rate among regions and lack of data from many countries. Data from this review can be used in the development of customized strategies for infection control and antimicrobial stewardship.

    Matched MeSH terms: Survival Analysis
  9. Djearamane S, Lim YM, Wong LS, Lee PF
    PeerJ, 2019;7:e7582.
    PMID: 31579572 DOI: 10.7717/peerj.7582
    Background: Zinc oxide nanoparticles (ZnO NPs) are widely used in household and cosmetic products which imply an increased releasing of these particles into the environment, especially aquatic ecosystems, resulting in the need of assessing the potential toxic effects of ZnO NPS on the aquatic organisms, particularly on microalgae which form the base for food chain of aquatic biota. The present study has investigated the dose- and time-dependent cellular accumulation and the corresponding cytotoxic effects of increasing concentrations of ZnO NPs from 10-200 μg/mL on microalga Haematococcus pluvialis at an interval of 24 h for 96 h.

    Methods: The scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX) was used to qualitatively detect the cellular accumulation of ZnO NPs in algal cells, while inductively coupled plasma optical emission spectrometry (ICP OES) was performed to quantify the cell associated-zinc in algal cells. The percentage of cell death, reduction in algal biomass, and loss in photosynthetic pigments were measured to investigate the cytotoxic effects of ZnO NPs on H. pluvialis. Extracellular and intracellular changes in algal cells resulted from the treatment of ZnO NPs were demonstrated through optical, scanning, and transmission electron microscopic studies.

    Results: SEM-EDX spectrum evidenced the accumulation of ZnO NPs in algal biomass and ICP OES results reported a significant (p < 0.05) dose- and time-dependent accumulation of zinc in algal cells from 24 h for all the tested concentrations of ZnO NPs (10-200 μg/mL). Further, the study showed a significant (p < 0.05) dose- and time-dependent growth inhibition of H. pluvialis from 72 h at 10-200 μg/mL of ZnO NPs. The morphological examinations revealed substantial surface and intracellular damages in algal cells due to the treatment of ZnO NPs.

    Discussion: The present study reported the significant cellular accumulation of ZnO NPs in algal cells and the corresponding cytotoxic effects of ZnO NPs on H. pluvialis through the considerable reduction in algal cell viability, biomass, and photosynthetic pigments together with surface and intracellular damages.

    Matched MeSH terms: Cell Survival
  10. Buskaran K, Bullo S, Hussein MZ, Masarudin MJ, Mohd Moklas MA, Fakurazi S
    Materials (Basel), 2021 Feb 09;14(4).
    PMID: 33572054 DOI: 10.3390/ma14040817
    Liver cancer is listed as the fifth-ranked cancer, responsible for 9.1% of all cancer deaths globally due to its assertive nature and poor survival rate. To overcome this obstacle, efforts have been made to ensure effective cancer therapy via nanotechnology utilization. Recent studies have shown that functionalized graphene oxide (GO)-loaded protocatechuic acid has shown some anticancer activities in both passive and active targeting. The nanocomposites' physicochemical characterizations were conducted. A lactate dehydrogenase experiment was conducted to estimate the severity of cell damage. Subsequently, a clonogenic assay was carried out to examine the colony-forming ability during long-term exposure of the nanocomposites. The Annexin V/ propidium iodide analysis showed that nanocomposites induced late apoptosis in HepG2 cells. Following the intervention of nanocomposites, cell cycle arrest was ascertained at G2/M phase. There was depolarization of mitochondrial membrane potential and an upregulation of reactive oxygen species when HepG2 cells were induced by nanocomposites. Finally, the proteomic profiling array and quantitative reverse transcription polymerase chain reaction revealed the expression of pro-apoptotic and anti-apoptotic proteins induced by graphene oxide conjugated PEG loaded with protocatechuic acid drug folic acid coated nanocomposite (GOP-PCA-FA) in HepG2 cells. In conclusion, GOP-PCA-FA nanocomposites treated HepG2 cells exhibited significant anticancer activities with less toxicity compared to pristine protocatechuic acid and GOP-PCA nanocomposites, due to the utilization of a folic acid-targeting nanodrug delivery system.
    Matched MeSH terms: Survival Rate
  11. Ahammad AKS, Asaduzzaman M, Uddin Ahmed MB, Akter S, Islam MS, Haque MM, et al.
    J Therm Biol, 2021 Feb;96:102830.
    PMID: 33627269 DOI: 10.1016/j.jtherbio.2020.102830
    Although indigenous climbing perch (Anabas testudineusis) is a highly valuable species, slow growth pattern during the culture period impeding its commercial success in aquaculture. In many fish species, it has been demonstrated that incubation temperature of eggs influenced the muscle development and growth rates, which persisted throughout the subsequent larval and juvenile phases. Therefore, this study aimed to investigate whether different incubation temperature of eggs prior to hatching can stimulate the muscle development, growth, and growth-related gene expression of the slow-growing indigenous species of climbing perch. The fertilized eggs of A. testudineus from an artificial breeding program were incubated under control temperature of 24 °C (IT24), 26 °C (IT26), 28 °C (IT28), and 30 °C (IT30) in 10L glass aquaria with four replicated units for each temperature treatment. After hatching, the larvae from each incubated temperature were separately reared at ambient temperature for 10 days in aquarium, 20 days in hapas, and the next 42 days in cages, totaling 72 days post-hatching (dph). The hatching rates were found significantly (P 
    Matched MeSH terms: Survival Rate
  12. Loh EYX, Fauzi MB, Ng MH, Ng PY, Ng SF, Mohd Amin MCI
    Int J Biol Macromol, 2020 Sep 15;159:497-509.
    PMID: 32387606 DOI: 10.1016/j.ijbiomac.2020.05.011
    In skin tissue engineering, a biodegradable scaffold is usually used where cells grow, produce its own cytokines, growth factors, and extracellular matrix, until the regenerated tissue gradually replaces the scaffold upon its degradation. However, the role of non-biodegradable scaffold remains unexplored. This study investigates the potential of a non-biodegradable bacterial nanocellulose/acrylic acid (BNC/AA) hydrogel to transfer human dermal fibroblasts (HDF) to the wound and the resulting healing effects of transferred HDF in athymic mice. Results demonstrated that the fabricated hydrogel successfully transferred >50% of HDF onto the wound site within 24 h, with evidence of HDF detected on day 7. The gene and protein study unveiled faster wound healing in the hydrogel with HDF group and characterized more mature newly formed skin microstructure on day 7, despite no visible differences. These findings give a new perspective regarding the role of non-biodegradable materials in skin tissue engineering, in the presence of exogenous cells, mainly at the molecular level.
    Matched MeSH terms: Cell Survival
  13. Woo YL, Kyrgiou M, Bryant A, Everett T, Dickinson HO
    Gynecol Oncol, 2012 Aug;126(2):286-90.
    PMID: 22507534 DOI: 10.1016/j.ygyno.2012.04.012
    Gynaecological cancers are the second most common cancers among women. It has been suggested that centralised care improves outcomes but consensus is lacking. This systematic review assesses the effectiveness of centralisation of care for patients with gynaecological cancer, in particular, survival advantage.
    Matched MeSH terms: Survival Analysis
  14. Albitar O, Ballouze R, Ooi JP, Sheikh Ghadzi SM
    Diabetes Res Clin Pract, 2020 Aug;166:108293.
    PMID: 32623035 DOI: 10.1016/j.diabres.2020.108293
    AIMS: COVID-19 is a current global pandemic. However, comprehensive global data analyses for its mortality risk factors are lacking. The current investigation aimed to assess the predictors of death among COVID-19 patients from worldwide open access data.

    METHODS: A total of 828 confirmed cases of COVID-19 with definite outcomes were retrospectively identified from open access individual-level worldwide data. Univariate followed by multivariable regression analysis were used to evaluate the association between potential risk factors and mortality.

    RESULTS: Majority of the patients were males 59.1% located in Asia 69.3%. Based on the data, older age (adjusted odds ratio (aOR), 1.079; 95% confidence intervals (95% CI), 1.064-1.095 per year increase), males (aOR, 1.607; 95% CI, 1.002-2.576), patients with hypertension (aOR, 3.576; 95% CI, 1.694-7.548), diabetes mellitus (aOR, 12.234; 95% CI, 4.126-36.272), and patients located in America (aOR, 7.441; 95% CI, 3.546-15.617) were identified as the risk factors of mortality among COVID-19 patients.

    CONCLUSIONS: Males, advanced age, hypertension patients, diabetes mellitus patients, and patients located in America were the independent risk factors of death among COVID-19 patients. Extra attention is required to be given to these factors and additional studies on the underlying mechanisms of these effects.

    Matched MeSH terms: Survival Rate
  15. Syukri Y, Taher M, Martien R, Lukitaningsih E, Nugroho AE, Zakaria ZA
    Adv Pharm Bull, 2021 Jan;11(1):171-180.
    PMID: 33747864 DOI: 10.34172/apb.2021.018
    Purpose:
    Insulin resistance is a characteristic of non-insulin-dependent diabetes mellitus associated with obesity and caused by the failure of pancreatic beta cells to secrete sufficient amount of insulin. Andrographolide (AND) improves beta-cell reconstruction and inhibits fat-cell formation. This research aimed to improve the delivery of water-insoluble AND in self-nanoemulsifying (ASNE) formulation, tested in streptozotocin (STZ)-induced diabetic rats and 3T3-L1 preadipocyte cells.
    Methods:
    A conventional formulation of AND in suspension was used as a control. The experimental rats were orally administered with self-nanoemulsifying (SNE) and suspension of AND for 8 days. Measurements were performed to evaluate blood glucose levels in preprandial and postprandial conditions. Immunohistochemistry was used to assess the process of islet beta cell reconstruction. In vitro study was performed using cell viability and adipocyte differentiation assay to determine the delivery of AND in the formulation.
    Results:
    ASNE lowered blood glucose levels (day 4) faster than AND suspension (day 6). The histological testing showed that ASNE could regenerate pancreatic beta cells. Therefore, ASNE ameliorated pancreatic beta cells. The in vitro evaluation indicated the inhibition of adipocyte differentiation by both AND and ASNE, which occurred in a time-dependent manner. ASNE formulation had better delivery than AND.
    Conclusion:
    ASNE could improve the antidiabetic activity by lowering blood glucose levels, enhancing pancreatic beta cells, and inhibiting lipid formation in adipocyte cells.
    Matched MeSH terms: Cell Survival
  16. Raja M, Yaacob Y, Wong Z, Chik I
    Med J Malaysia, 2021 03;76(2):151-156.
    PMID: 33742621
    INTRODUCTION: Hepatocellular carcinoma (HCC) is among the common death-causing cancers worldwide. This liver malignancy is primarily diagnosed using radiological imaging techniques. Most of the patients in Malaysia present late and were diagnosed at an intermediate or advanced stage of Barcelona Clinic of Liver Cancer (BCLC). This causes a limitation on the treatment options for the patients.

    MATERIALS AND METHODS: We performed a retrospective crosssectional study of HCC cases within a five-year period in our center with data collected from Hospital Canselor Tunku Mukhriz (HCTM). This study examines the HCC risk factors, the pattern of diagnosis, treatment options and overall survival.

    RESULTS: The findings from this study showed that viral hepatitis was the highest risk factor in which most of the patients were elderly males who presented with abdominal distension. In addition, given the high prevalence of metabolic diseases Malaysia, it is predicted that the number of non-alcoholic steatohepatosis (NASH)-related HCC cases might increase. Alpha-fetoprotein (AFP) proved to have no significant role in the detection of the disease. The number of patients detected at early BCLC was minimal, resulting in limited options of treatment. Overall survival of our HCC patients was poor at 17 months.

    CONCLUSION: We conclude that HCC patients in HCTM mostly presented at late stage to hospital, hence limiting the treatment options and resulted in poor survival rate. Disease awareness should be implemented at primary care level to detect HCC at its early stage. Subsequently, a multidisciplinary hospital team is required to manage the disease at its different stages of presentation.

    Matched MeSH terms: Survival Rate
  17. Osahor AN, Narayanan K
    Methods Mol Biol, 2021;2211:15-27.
    PMID: 33336267 DOI: 10.1007/978-1-0716-0943-9_2
    Gene delivery using invasive bacteria as vectors is a robust method that is feasible for plasmid and artificial chromosome DNA construct delivery to human cells presenting β1 integrin receptors. This technique is relatively underutilized owing to the inefficiency of gene transfer to targeted cell populations. Bacterial vectors must successfully adhere to the cell membrane, internalize into the cytoplasm, undergo lysis, and deliver DNA to the nucleus. There are limited studies on the use of exogenous reagents to improve the efficiency of bacteria-mediated gene delivery to mammalian cells. In this chapter, we describe how cationic lipids, conventionally used for DNA and protein transfection, as well as antimicrobial compounds, can be used to synergistically enhance the adherence of invasive bacterial vectors to the cell membrane and improve their predisposition to internalize into the cytoplasm to deliver DNA. Using simple combinatorial methods, functional DNA transfer can be improved by up to four-fold of invaded cell populations. These methods are easy to perform and are likely to be applicable for other bacterial vectors including Listeria and Salmonella.
    Matched MeSH terms: Cell Survival
  18. Masood A, Maheen S, Khan HU, Shafqat SS, Irshad M, Aslam I, et al.
    ACS Omega, 2021 Mar 30;6(12):8210-8225.
    PMID: 33817480 DOI: 10.1021/acsomega.0c06242
    The current research aimed at designing mesoporous silica nanoparticles (MSNs) for a controlled coadministration of salicylic acid (SA) and ketoconazole (KCZ) to effectively treat highly resistant fungal infections. The sol-gel method was used to formulate MSNs, which were further optimized using central composite rotatable design (CCRD) by investigating mathematical impact of independent formulation variables such as pH, stirring time, and stirring speed on dependent variables entrapment efficiency (EE) and drug release. The selected optimized MSNs and pure drugs were subjected to comparative in vitro/in vivo antifungal studies, skin irritation, cytotoxicity, and histopathological evaluations. The obtained negatively charged (-23.1), free flowing spherical, highly porous structured MSNs having a size distribution of 300-500 nm were suggestive of high storage stability and improved cell proliferation due to enhanced oxygen supply to cells. The physico-chemical evaluation of SA/KCZ-loaded MSNs performed through powder X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR), and thermal gravimetric analysis (TGA) indicates absolute lack of any interaction between formulation components and successful encapsulation of both drugs in MSNs. The EESA, EEKCZ, SA release, and KCZ release varied significantly from 34 to 89%, 36 to 85%, 39 to 88%, and 43 to 90%, respectively, indicating the quadratic impact of formulation variables on obtained MSNs. For MSNs, the skin tolerability and cell viability percentage rate were also having an extraordinary advantage over suspension of pure drugs. The optimized SA/KCZ-loaded MSNs demonstrated comparatively enhanced in vitro/in vivo antifungal activities and rapid wound healing efficacy in histopathological evaluation without any skin irritation impact, suggesting the MSNs potential for the simultaneous codelivery of antifungal and keratolyic agents in sustained release fashion.
    Matched MeSH terms: Cell Survival
  19. Abd Ghani MF, Othman R, Nordin N
    J Pharm Bioallied Sci, 2020 Nov;12(Suppl 2):S676-S680.
    PMID: 33828360 DOI: 10.4103/jpbs.JPBS_272_19
    The naturally derived flavonoids are well known to have anticarcinogenic effects. Flavonoids could be an alternative strategy for ovarian cancer treatment, due to existing platinum-based drugs are reported to develop resistance with low survival rates. Inhibition of antiapoptotic proteins, namely B-cell lymphoma (Bcl-2) and B-cell lymphoma-extra large (Bcl-xl), is the key target to stimulate apoptosis process in cancer cells. This study aimed to determine the binding interaction of five naturally derived flavonoids (biochanin A, myricetin, apigenin, galangin, and fisetin) with potential antiapoptotic target proteins (Bcl-2 and Bcl-xl). The molecular docking study was conducted using AutoDock Vina program. The binding affinity and the presence of hydrogen bonds between the flavonoids and target proteins were predicted. Our findings showed that all the flavonoids showed better binding affinity with Bcl-xl than that of Bcl-2 proteins. The highest binding affinity was recorded in fisetin-Bcl-xl protein complex (-8.8 kcal/mol). Meanwhile, the other flavonoids docked with Bcl-xl protein showed binding affinities, ranging from -8.0 to -8.6 kcal/mol. A total of four hydrogen bonds, four hydrophobic contacts, and one electrostatic interaction were detected in the docked fisetin-Bcl-xl complex, explaining its high binding affinity with Bcl-xl. The present results indicate that all flavonoids could potentially serve as Bcl-xl protein inhibitors, which would consequently lead to apoptotic process in ovarian cancers.
    Matched MeSH terms: Survival Rate
  20. Ang YLE, Ho GF, Soo RA, Sundar R, Tan SH, Yong WP, et al.
    BMC Cancer, 2020 Nov 17;20(1):1118.
    PMID: 33203399 DOI: 10.1186/s12885-020-07616-4
    BACKGROUND: We previously reported that low-dose, short-course sunitinib prior to neoadjuvant doxorubicin-cyclophosphamide (AC) normalised tumour vasculature and improved perfusion, but resulted in neutropenia and delayed subsequent cycles in breast cancer patients. This study combined sunitinib with docetaxel, which has an earlier neutrophil nadir than AC.

    METHODS: Patients with advanced solid cancers were randomized 1:1 to 3-weekly docetaxel 75 mg/m2, with or without sunitinib 12.5 mg daily for 7 days prior to docetaxel, stratified by primary tumour site. Primary endpoints were objective-response (ORR:CR + PR) and clinical-benefit rate (CBR:CR + PR + SD); secondary endpoints were toxicity and progression-free-survival (PFS).

    RESULTS: We enrolled 68 patients from 2 study sites; 33 received docetaxel-sunitinib and 35 docetaxel alone, with 33 breast, 25 lung and 10 patients with other cancers. There was no difference in ORR (30.3% vs 28.6%, p = 0.432, odds-ratio [OR] 1.10, 95% CI 0.38-3.18); CBR was lower in the docetaxel-sunitinib arm (48.5% vs 71.4%, p = 0.027 OR 0.37, 95% CI 0.14-1.01). Median PFS was shorter in the docetaxel-sunitinib arm (2.9 vs 4.9 months, hazard-ratio [HR] 2.00, 95% CI 1.15-3.48, p = 0.014) overall, as well as in breast (4.2 vs 5.6 months, p = 0.048) and other cancers (2.0 vs 5.3 months, p = 0.009), but not in lung cancers (2.9 vs 4.1 months, p = 0.597). Median OS was similar in both arms overall (9.9 vs 10.5 months, HR 0.92, 95% CI 0.51-1.67, p = 0.789), and in the breast (18.9 vs 25.8 months, p = 0.354), lung (7.0 vs 6.7 months, p = 0.970) and other cancers (4.5 vs 8.8 months, p = 0.449) subgroups. Grade 3/4 haematological toxicities were lower with docetaxel-sunitinib (18.2% vs 34.3%, p = 0.132), attributed to greater discretionary use of prophylactic G-CSF (90.9% vs 63.0%, p = 0.024). Grade 3/4 non-haematological toxicities were similar (12.1% vs 14.3%, p = 0.792).

    CONCLUSIONS: The addition of sunitinib to docetaxel was well-tolerated but did not improve outcomes. The possible negative impact in metastatic breast cancer patients is contrary to results of adding sunitinib to neoadjuvant AC. These negative results suggest that the intermittent administration of sunitinib in the current dose and schedule with docetaxel in advanced solid tumours, particularly breast cancers, is not beneficial.

    TRIAL REGISTRATION: The study was registered ( NCT01803503 ) prospectively on clinicaltrials.gov on 4th March 2013.

    Matched MeSH terms: Survival Rate
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