Displaying publications 301 - 320 of 812 in total

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  1. Fulltext Recent Emergence of Rhenium(I) Tricarbonyl Complexes as Photosensitisers for Cancer Therapy
    Liew HS, Mai CW, Zulkefeli M, Madheswaran T, Kiew LV, Delsuc N, et al.
    Molecules, 2020 Sep 12;25(18).
    PMID: 32932573 DOI: 10.3390/molecules25184176
    Photodynamic therapy (PDT) is emerging as a significant complementary or alternative approach for cancer treatment. PDT drugs act as photosensitisers, which upon using appropriate wavelength light and in the presence of molecular oxygen, can lead to cell death. Herein, we reviewed the general characteristics of the different generation of photosensitisers. We also outlined the emergence of rhenium (Re) and more specifically, Re(I) tricarbonyl complexes as a new generation of metal-based photosensitisers for photodynamic therapy that are of great interest in multidisciplinary research. The photophysical properties and structures of Re(I) complexes discussed in this review are summarised to determine basic features and similarities among the structures that are important for their phototoxic activity and future investigations. We further examined the in vitro and in vivo efficacies of the Re(I) complexes that have been synthesised for anticancer purposes. We also discussed Re(I) complexes in conjunction with the advancement of two-photon PDT, drug combination study, nanomedicine, and photothermal therapy to overcome the limitation of such complexes, which generally absorb short wavelengths.
    Matched MeSH terms: Neoplasms/drug therapy*
  2. G2/M cell cycle arrest on HT-29 cancer cells and toxicity assessment of triphenylphosphanegold(I) carbonimidothioates, Ph3PAu[SC(OR)=NPh], R=Me, Et, and iPr, during zebrafish development
    Ooi KK, Yeo CI, Mahandaran T, Ang KP, Akim AM, Cheah YK, et al.
    J Inorg Biochem, 2017 01;166:173-181.
    PMID: 27865929 DOI: 10.1016/j.jinorgbio.2016.11.008
    Phosphanegold(I) thiolates, Ph3PAu[SC(OR)=NPh], R=Me (1), Et (2) and iPr (3), were previously shown to be significantly cytotoxic toward HT-29 cancer cells and to induce cell death by both intrinsic and extrinsic apoptotic pathways whereby 1 activated the p73 gene, and each of 2 and 3 activated p53; 2 also caused apoptotic cell death via the c-Jun N-terminal kinase/mitogen-activated protein kinase pathway. Apoptosis pathways have been further evaluated by mitochondrial cytochrome c measurements and annexin V screening, confirming apoptotic pathways of cell death. Cell cycle analysis showed the majority of treated HT-29 cells were arrested at the G2/M checkpoint after 24h; results of both assays were confirmed by changes in populations of relevant genes (PCR array analysis). Cell invasion studies showed inhibition of metastasis through Matrigel™ matrix to 17-22% cf. untreated cells. LC50values were determined in zebrafish (8.36, 8.17, and 7.64μM for 1-3). Finally, the zebrafish tolerated doses of 1 and 2 up to 0.625μM, and 3 was tolerated at even higher doses of up to 1.25μM.
    Matched MeSH terms: Neoplasms/drug therapy*
  3. The influence of R substituents in triphenylphosphinegold(I) carbonimidothioates, Ph3PAu[SC(OR)=NPh] (R=Me, Et and iPr), upon in vitro cytotoxicity against the HT-29 colon cancer cell line and upon apoptotic pathways
    Yeo CI, Ooi KK, Akim AM, Ang KP, Fairuz ZA, Halim SN, et al.
    J Inorg Biochem, 2013 Oct;127:24-38.
    PMID: 23850666 DOI: 10.1016/j.jinorgbio.2013.05.011
    The Ph3PAu[SC(OR)=NPh], R=Me (1), Et (2) and iPr (3), compounds are significantly cytotoxic to the HT-29 cancer cell line with 1 being the most active. Based on human apoptosis PCR-array analysis, caspase activities, DNA fragmentation, cell apoptotic assays, intracellular reactive oxygen species (ROS) measurements and human topoisomerase I inhibition, induction of apoptosis is demonstrated and both the extrinsic and intrinsic pathways of apoptosis have been shown to occur. Compound 1 activates the p73 gene, whereas each of 2 and 3 activates the p53 gene. An additional apoptotic mechanism is exhibited by 2, that is, via the JNK/MAP pathway.
    Matched MeSH terms: Colonic Neoplasms/drug therapy*
  4. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study
    Burtness B, Harrington KJ, Greil R, Soulières D, Tahara M, de Castro G, et al.
    Lancet, 2019 11 23;394(10212):1915-1928.
    PMID: 31679945 DOI: 10.1016/S0140-6736(19)32591-7
    BACKGROUND: Pembrolizumab is active in head and neck squamous cell carcinoma (HNSCC), with programmed cell death ligand 1 (PD-L1) expression associated with improved response.

    METHODS: KEYNOTE-048 was a randomised, phase 3 study of participants with untreated locally incurable recurrent or metastatic HNSCC done at 200 sites in 37 countries. Participants were stratified by PD-L1 expression, p16 status, and performance status and randomly allocated (1:1:1) to pembrolizumab alone, pembrolizumab plus a platinum and 5-fluorouracil (pembrolizumab with chemotherapy), or cetuximab plus a platinum and 5-fluorouracil (cetuximab with chemotherapy). Investigators and participants were aware of treatment assignment. Investigators, participants, and representatives of the sponsor were masked to the PD-L1 combined positive score (CPS) results; PD-L1 positivity was not required for study entry. The primary endpoints were overall survival (time from randomisation to death from any cause) and progression-free survival (time from randomisation to radiographically confirmed disease progression or death from any cause, whichever came first) in the intention-to-treat population (all participants randomly allocated to a treatment group). There were 14 primary hypotheses: superiority of pembrolizumab alone and of pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival and progression-free survival in the PD-L1 CPS of 20 or more, CPS of 1 or more, and total populations and non-inferiority (non-inferiority margin: 1·2) of pembrolizumab alone and pembrolizumab with chemotherapy versus cetuximab with chemotherapy for overall survival in the total population. The definitive findings for each hypothesis were obtained when statistical testing was completed for that hypothesis; this occurred at the second interim analysis for 11 hypotheses and at final analysis for three hypotheses. Safety was assessed in the as-treated population (all participants who received at least one dose of allocated treatment). This study is registered at ClinicalTrials.gov, number NCT02358031.

    FINDINGS: Between April 20, 2015, and Jan 17, 2017, 882 participants were allocated to receive pembrolizumab alone (n=301), pembrolizumab with chemotherapy (n=281), or cetuximab with chemotherapy (n=300); of these, 754 (85%) had CPS of 1 or more and 381 (43%) had CPS of 20 or more. At the second interim analysis, pembrolizumab alone improved overall survival versus cetuximab with chemotherapy in the CPS of 20 or more population (median 14·9 months vs 10·7 months, hazard ratio [HR] 0·61 [95% CI 0·45-0·83], p=0·0007) and CPS of 1 or more population (12·3 vs 10·3, 0·78 [0·64-0·96], p=0·0086) and was non-inferior in the total population (11·6 vs 10·7, 0·85 [0·71-1·03]). Pembrolizumab with chemotherapy improved overall survival versus cetuximab with chemotherapy in the total population (13·0 months vs 10·7 months, HR 0·77 [95% CI 0·63-0·93], p=0·0034) at the second interim analysis and in the CPS of 20 or more population (14·7 vs 11·0, 0·60 [0·45-0·82], p=0·0004) and CPS of 1 or more population (13·6 vs 10·4, 0·65 [0·53-0·80], p<0·0001) at final analysis. Neither pembrolizumab alone nor pembrolizumab with chemotherapy improved progression-free survival at the second interim analysis. At final analysis, grade 3 or worse all-cause adverse events occurred in 164 (55%) of 300 treated participants in the pembrolizumab alone group, 235 (85%) of 276 in the pembrolizumab with chemotherapy group, and 239 (83%) of 287 in the cetuximab with chemotherapy group. Adverse events led to death in 25 (8%) participants in the pembrolizumab alone group, 32 (12%) in the pembrolizumab with chemotherapy group, and 28 (10%) in the cetuximab with chemotherapy group.

    INTERPRETATION: Based on the observed efficacy and safety, pembrolizumab plus platinum and 5-fluorouracil is an appropriate first-line treatment for recurrent or metastatic HNSCC and pembrolizumab monotherapy is an appropriate first-line treatment for PD-L1-positive recurrent or metastatic HNSCC.

    FUNDING: Merck Sharp & Dohme.

    Matched MeSH terms: Head and Neck Neoplasms/drug therapy*
  5. Rutin loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro
    Paudel KR, Wadhwa R, Tew XN, Lau NJX, Madheswaran T, Panneerselvam J, et al.
    Life Sci, 2021 Jul 01;276:119436.
    PMID: 33789146 DOI: 10.1016/j.lfs.2021.119436
    Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality globally. Despite the availability of therapeutic options, the improvement in patient survival is yet to be achieved. Recent advances in natural product (e.g., Rutin) research, therapeutic nanotechnology and especially the combination of both could aid in achieving significant improvements in the treatment or management of NSCLC. In this study, we explore the anti-cancer activity of Rutin-loaded liquid crystalline nanoparticles (LCNs) in an in vitro model where we have employed the A549 human lung epithelial carcinoma cell line. The anti-proliferative activity was determined by MTT and Trypan blue assays, whereas, the anti-migratory activity was evaluated by the scratch wound healing assay and a modified Boyden chamber assay. We also evaluated the anti-apoptotic activity by Annexin V-FITC staining, and the colony formation activity was studied using crystal violet staining. Here, we report that Rutin-LCNs showed promising anti-proliferative and anti-migratory activities. Furthermore, Rutin-LCNs also induced apoptosis in the A549 cells and inhibited colony formation. The findings warrant further detailed and in-depth anti-cancer mechanistic studies of Rutin-LCNs with a focus towards a potential therapeutic option for NSCLC. LCNs may help to enhance the solubility of Rutin used in the treatment of lung cancer and hence enhance the anticancer effect of Rutin.
    Matched MeSH terms: Lung Neoplasms/drug therapy*
  6. The Potential Use of Anticancer Peptides (ACPs) in the Treatment of Hepatocellular Carcinoma
    Ng CX, Lee SH
    Curr Cancer Drug Targets, 2020;20(3):187-196.
    PMID: 31713495 DOI: 10.2174/1568009619666191111141032
    Peptides have acquired increasing interest as promising therapeutics, particularly as anticancer alternatives during recent years. They have been reported to demonstrate incredible anticancer potentials due to their low manufacturing cost, ease of synthesis and great specificity and selectivity. Hepatocellular carcinoma (HCC) is among the leading cause of cancer death globally, and the effectiveness of current liver treatment has turned out to be a critical issue in treating the disease efficiently. Hence, new interventions are being explored for the treatment of hepatocellular carcinoma. Anticancer peptides (ACPs) were first identified as part of the innate immune system of living organisms, demonstrating promising activity against infectious diseases. Differentiated beyond the traditional effort on endogenous human peptides, the discovery of peptide drugs has evolved to rely more on isolation from other natural sources or through the medicinal chemistry approach. Up to the present time, the pharmaceutical industry intends to conduct more clinical trials for the development of peptides as alternative therapy since peptides possess numerous advantages such as high selectivity and efficacy against cancers over normal tissues, as well as a broad spectrum of anticancer activity. In this review, we present an overview of the literature concerning peptide's physicochemical properties and describe the contemporary status of several anticancer peptides currently engaged in clinical trials for the treatment of hepatocellular carcinoma.
    Matched MeSH terms: Liver Neoplasms/drug therapy*
  7. Fulltext Anti-Uterine Fibroid Effect of Standardized Labisia Pumila Var. Alata Extracts In Vitro and in Human Uterine Fibroid Cancer Xenograft Model
    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: Uterine Neoplasms/drug therapy*
  8. Fulltext Cytotoxic Activity of Christia vespertilionis Root and Leaf Extracts and Fractions against Breast Cancer Cell Lines
    Lee JJ, Saiful Yazan L, Kassim NK, Che Abdullah CA, Esa N, Lim PC, et al.
    Molecules, 2020 Jun 04;25(11).
    PMID: 32512700 DOI: 10.3390/molecules25112610
    Christia vespertilionis, commonly known as 'Daun Rerama', has recently garnered attention from numerous sources in Malaysia as an alternative treatment. Its herbal decoction was believed to show anti-inflammatory and anti-cancer effects. The present study investigated the cytotoxicity of the extract of root and leaf of C. vespertilionis. The plant parts were successively extracted using the solvent maceration method. The most active extract was further fractionated to afford F1-F8. The cytotoxic effects were determined using MTT assay against human breast carcinoma cell lines (MCF-7 and MDA-MB-231). The total phenolic content (TPC) of the extracts were determined. The antioxidant properties of the extract were also studied using DPPH and β-carotene bleaching assays. The ethyl acetate root extract demonstrated selective cytotoxicity especially against MDA-MB-231 with the highest TPC and antioxidant properties compared to others (p < 0.05). The TPC and antioxidant results suggest the contribution of phenolic compounds toward its antioxidant strength leading to significant cytotoxicity. F3 showed potent cytotoxic effects while F4 showed better antioxidative strength compared to others (p < 0.05). Qualitative phytochemical screening of the most active fraction, F3, suggested the presence of flavonoids, coumarins and quinones to be responsible toward the cytotoxicity. The study showed the root extracts of C. vespertilionis to possess notable anti-breast cancer effects.
    Matched MeSH terms: Breast Neoplasms/drug therapy
  9. The influence of genetic polymorphisms on the efficacy and side effects of anastrozole in postmenopausal breast cancer patients
    Abubakar MB, Wei K, Gan SH
    Pharmacogenet Genomics, 2014 Dec;24(12):575-81.
    PMID: 25203739 DOI: 10.1097/FPC.0000000000000092
    Breast cancer is a common cause of cancer mortality among women. Several genetic factors have been implicated in its development. Current treatment guidelines for estrogen receptor-positive breast cancer recommend that anastrozole [or any of the other two aromatase inhibitors (letrozole and exemestane)] is used as an alternative to tamoxifen or following several years of tamoxifen treatment. Nevertheless, this approach is still associated with many challenges, ranging from the recurrence of breast cancer to considerable interindividual variability in the tolerability of anastrozole, which may cause adverse effects, such as musculoskeletal symptoms, and lead to the withdrawal of many patients from treatment. Variabilities in the genes encoding the drug target (aromatase) or its metabolizing enzymes (CYP3A and UGT1A) contribute toward the interindividual variability in anastrozole's pharmacokinetics and/or pharmacodynamics. This paper reviews the role of genetic polymorphisms of CYP19A1, CYP3A4, and UGT1A4 in the responses of female hormone receptor-positive postmenopausal breast cancer patients to anastrozole. Many reviews in the literature have suggested that the study of functional polymorphisms and investigation of relevant genetic markers may provide valuable information in predicting responses to anastrozole in terms of its therapeutic and adverse effects. Nevertheless, more studies are required before the knowledge of its pharmacogenomics can be applied to the individualization of treatment to ensure that patients receive the maximum benefits. Therefore, future analyses, including but not limited to genome-wide association studies, are encouraged to address some of the gray areas in the pharmacogenomics of anastrozole therapy in postmenopausal breast cancer cases; this will help in providing guidance for future pharmacogenomics protocols when anastrozole is utilized in patients' management.
    Matched MeSH terms: Breast Neoplasms/drug therapy*
  10. Suppression of BCL-2 synergizes cisplatin sensitivity in nasopharyngeal carcinoma cells
    Low SY, Tan BS, Choo HL, Tiong KH, Khoo AS, Leong CO
    Cancer Lett, 2012 Jan 28;314(2):166-75.
    PMID: 22033244 DOI: 10.1016/j.canlet.2011.09.025
    The efficacy of cisplatin for treating nasopharyngeal carcinoma (NPC) is limited by the dose-related toxicities and the development of resistance to cisplatin. Recent studies have shown that B cell lymphoma-2 (BCL-2) is overexpressed and confers chemoresistance in NPC. Thus, targeted therapy against BCL-2 may enhance the antitumour effects of chemotherapy by sensitizing the tumor cells to undergo apoptosis. This study evaluated the combined effects of BCL-2 inhibition and cisplatin in NPC cells. Our results demonstrate that inhibition of BCL-2 by small-hairpin RNA (shRNA) or the BCL-2 inhibitor YC137, synergizes cisplatin sensitivity in NPC cells that overexpress BCL-2. We also show that YC137 enhance cisplatin-induced apoptosis in HK1 and CNE1 cells through suppression of BCL-2 protein expression, induction of mitochondrial depolarization and activation of caspase 9 and caspase 3/7. These findings suggest that the combination of BCL-2 inhibition and cisplatin represents a promising strategy for treating NPC.
    Matched MeSH terms: Nasopharyngeal Neoplasms/drug therapy*
  11. Multitargeted therapy of cancer by tocotrienols
    Nesaretnam K
    Cancer Lett, 2008 Oct 8;269(2):388-95.
    PMID: 18504069 DOI: 10.1016/j.canlet.2008.03.063
    Natural compounds with possible health benefits have become attractive targets for research in areas pertaining to human health. For both prevention and therapy of various human ailments, such compounds are preferred over synthetic ones due to their lesser toxicity. They are also easily absorbed and processed by our body. Vitamins are prominent among natural or endogenous compounds that are considered to be beneficial. The vitamin E group of compounds is among the better known of the vitamins due to their suggested health benefits including antioxidant and related protective properties. Among these, tocotrienols have gained prominence in recent years due to their potential applications and better protective effects in certain systems. These tocotrienols are vitamin E derivatives that are analogs of the more established forms of vitamin E namely tocopherols. In addition to their potent antioxidant activity, tocotrienols have other important functions, especially in maintaining a healthy cardiovascular system and a possible role in protection against cancer and other ailments.
    Matched MeSH terms: Neoplasms/drug therapy*
  12. Synthesis and Characterization of PLGA-PEG Thymoquinone Nanoparticles and Its Cytotoxicity Effects in Tamoxifen-Resistant Breast Cancer Cells
    Ahmad R, Kaus NHM, Hamid S
    Adv Exp Med Biol, 2020;1292:65-82.
    PMID: 30560443 DOI: 10.1007/5584_2018_302
    INTRODUCTION: Drug resistance has been a continuous challenge in cancer treatment. The use of nanotechnology in the development of new cancer drugs has potential. One of the extensively studied compounds is thymoquinone (TQ), and this work aims to compare two types of TQ-nanoformulation and its cytotoxicity toward resistant breast cancer cells.

    METHOD: TQ-nanoparticles were prepared and optimized by using two different formulations with different drugs to PLGA-PEG ratio (1:20 and 1:7) and different PLGA-PEG to Pluronic F68 ratio (10:1 and 2:1). The morphology and size were determined using TEM and DLS. Characterization of particles was done using UV-VIS, ATR-IR, entrapment efficiency, and drug release. The effects of drug, polymer, and surfactants were compared between the two formulations. Cytotoxicity assay was performed using MTS assay.

    RESULTS: TEM finding showed 96% of particles produced with 1:7 drug to PLGA-PEG were less than 90 nm in size and spherical in shape. This was confirmed with DLS which showed smaller particle size than those formed with 1:20 drug to PLGA-PEG ratio. Further analysis showed zeta potential was negatively charged which could facilitate cellular uptake as reported previously. In addition, PDI value was less than 0.1 in both formulations indicating monodispersed and less broad in size distribution. The absorption peak of PLGA-PEG-TQ-Nps was at 255 nm. The 1:7 drug to polymer formulation was selected for further analysis where the entrapment efficiency was 79.9% and in vitro drug release showed a maximum release of TQ of 50%. Cytotoxicity result showed IC50 of TQ-nanoparticle at 20.05 μM and free TQ was 8.25 μM.

    CONCLUSION: This study showed that nanoparticle synthesized with 1:7 drug to PLGA-PEG ratio and 2:1 PLGA-PEG to Pluronic F68 formed nanoparticles with less than 100 nm and had spherical shape as confirmed with DLS. This could facilitate its transportation and absorption to reach its target. There was conserved TQ stability as exhibited slow release of this volatile oil. The TQ-nanoparticles showed selective cytotoxic effect toward UACC 732 cells compared to MCF-7 breast cancer cells.

    Matched MeSH terms: Breast Neoplasms/drug therapy*
  13. Multiple asymptomatic vascular air embolisms following contrast-enhanced CT scan
    Zulkifle AM, Faisal M
    BMJ Case Rep, 2019 Aug 28;12(8).
    PMID: 31466969 DOI: 10.1136/bcr-2018-229169
    Vascular air embolism (VAE) is a known complication of contrast-enhanced CT (CECT) scan occurring in venous or arterial circulation with a wide spectrum of presentations. We report a case of a 44-year-old woman with endometrial adenocarcinoma stage IVB complicated with liver abscess and pulmonary embolism who developed VAE following a routine CECT scan after the sixth cycle of chemotherapy. This was an incidental finding and the patient remained asymptomatic throughout. As such, she was treated conservatively and gradually recovered. This case report serves as a reminder that VAE should be considered in patients presenting with unexplained symptoms following this procedure.
    Matched MeSH terms: Endometrial Neoplasms/drug therapy*
  14. Antineoplastic-related cardiovascular toxicity: A systematic review and meta-analysis in Asia
    Leong SL, Chaiyakunapruk N, Lee SWH
    Crit Rev Oncol Hematol, 2019 Sep;141:95-101.
    PMID: 31272046 DOI: 10.1016/j.critrevonc.2019.05.017
    BACKGROUND: Cancer and heart diseases are the leading causes of morbidity and mortality in many countries worldwide. Recent advancement in chemotherapy and targeted therapies has led to an improvement in cancer survival rates, but at a cost of higher cardiac side effects. However, report on antineoplastic-related cardiotoxicities incidence in Asia is lacking.

    METHODS: We systematically searched multiple databases to identify studies reporting incidence of antineoplastic-related cardiovascular toxicity in Asia published from inception to November 2018. Pre-specified subgroups were performed to explore heterogeneity and study quality assessed and reported according to PRISMA guidelines.

    RESULTS: A total of 61 studies across 11 countries in Asia reported 8 types of cardiovascular toxicities were included. These studies mostly reported on adult populations, and usually examined cardiotoxicities related to anthracycline use. The most frequently reported cardiotoxicities were heart failure, electrocardiogram abnormalities and left ventricular dysfunction. The pooled estimated incidence of cardiotoxicity was 4.27% (95% CI: 3.53-5.07). Subgroup analysis showed higher incidence in middle income countries compared to high income countries.

    CONCLUSIONS: Although robust incidence studies are sparse, cardiovascular complications affects approximately one in twenty cancer patients in Asia. This highlights a unique opportunity of cancer patients caring that need cardiologists and oncologist to become familiar with this emerging sub-specialty.

    Matched MeSH terms: Neoplasms/drug therapy*
  15. Potential of dihydropyrimidine dehydrogenase genotypes in personalizing 5-fluorouracil therapy among colorectal cancer patients
    Teh LK, Hamzah S, Hashim H, Bannur Z, Zakaria ZA, Hasbullani Z, et al.
    Ther Drug Monit, 2013 Oct;35(5):624-30.
    PMID: 23942539 DOI: 10.1097/FTD.0b013e318290acd2
    Dihydropyrimidine dehydrogenase (DPD) is a pyrimidine catabolic enzyme involved in the initial and rate-limiting step of the catabolic pathway of toxic metabolites of 5-fluorouracil (5-FU). Several studies have reported that deficiency of DPD and polymorphisms of its gene are related to 5-FU toxicities and death. Association between serum concentration of 5-FU and its related toxicity has also been previously demonstrated. Hence, this study aims to understand the role of DPYD variants in serum level of 5-FU and the risk of developing toxicity to prevent adverse reactions and maximize therapy outcome for personalized medicine.
    Matched MeSH terms: Colorectal Neoplasms/drug therapy*
  16. Fulltext Is tissue still the issue in detecting molecular alterations in lung cancer?
    Liam CK, Mallawathantri S, Fong KM
    Respirology, 2020 09;25(9):933-943.
    PMID: 32335992 DOI: 10.1111/resp.13823
    Molecular biomarker testing of advanced-stage NSCLC is now considered standard of care and part of the diagnostic algorithm to identify subsets of patients for molecular-targeted treatment. Tumour tissue biopsy is essential for an accurate initial diagnosis, determination of the histological subtype and for molecular testing. With the increasing use of small biopsies and cytological specimens for diagnosis and the need to identify an increasing number of predictive biomarkers, proper management of the limited amount of sampling materials available is important. Many patients with advanced NSCLC do not have enough tissue for molecular testing and/or do not have a biopsy-amenable lesion and/or do not want to go through a repeat biopsy given the potential risks. Molecular testing can be difficult or impossible if the sparse material from very small biopsy specimens has already been exhausted for routine diagnostic purposes. A limited diagnostic workup is recommended to preserve sufficient tissue for biomarker testing. In addition, tumour biopsies are limited by tumour heterogeneity, particularly in the setting of disease resistance, and thus may yield false-negative results. Hence, there have been considerable efforts to determine if liquid biopsy in which molecular alterations can be non-invasively identified in plasma cell-free ctDNA, a potential surrogate for the entire tumour genome, can overcome the issues with tissue biopsies and replace the need for the latter.
    Matched MeSH terms: Lung Neoplasms/drug therapy
  17. Fulltext Modified J-CAPRA scoring system in predicting treatment outcomes of metastatic prostate cancer patients undergoing androgen deprivation therapy
    Lim J, Hinotsu S, Onozawa M, Malek R, Sundram M, Teh GC, et al.
    Cancer Med, 2020 12;9(24):9346-9352.
    PMID: 33098372 DOI: 10.1002/cam4.3548
    The J-CAPRA score is an assessment tool which stratifies risk and predicts outcome of primary androgen deprivation therapy (ADT) using prostate-specific antigen, Gleason score, and clinical TNM staging. Here, we aimed to assess the generalisability of this tool in multi-ethnic Asians. Performance of J-CAPRA was evaluated in 782 Malaysian and 16,946 Japanese patients undergoing ADT from the Malaysian Study Group of Prostate Cancer (M-CaP) and Japan Study Group of Prostate Cancer (J-CaP) databases, respectively. Using the original J-CAPRA, 69.6% metastatic (M1) cases without T and/or N staging were stratified as intermediate-risk disease in the M-CaP database. To address this, we first omitted clinical T and N stage variables, and calculated the score on a 0-8 scale in the modified J-CAPRA scoring system for M1 patients. Notably, treatment decisions of M1 cases were not directly affected by both T and N staging. The J-CAPRA score threshold was adjusted for intermediate (modified J-CAPRA score 3-5) and high-risk (modified J-CAPRA score ≥6) groups in M1 patients. Using J-CaP database, validation analysis showed that overall survival, prostate cancer-specific survival, and progression-free survival of modified intermediate and high-risk groups were comparable to those of original J-CAPRA (p > 0.05) with Cohen's coefficient of 0.65. Around 88% M1 cases from M-CaP database were reclassified into high-risk category. Modified J-CAPRA scoring system is instrumental in risk assessment and treatment outcome prediction for M1 patients without T and/or N staging.
    Matched MeSH terms: Prostatic Neoplasms/drug therapy*
  18. Fulltext Mechanistic Actions between Garcinia atroviridis Essential Oil and 2 Deoxy-d-glucose in Cultured PANC-1 Human Pancreatic Cancer Cells
    Nik Mohamed Kamal NNS, Abdul Aziz FA, Tan WN, Fauzi AN, Lim V
    Molecules, 2021 Jun 09;26(12).
    PMID: 34207699 DOI: 10.3390/molecules26123518
    Pancreatic cancer is an aggressive disease that progresses in a relatively symptom-free manner; thus, is difficult to detect and treat. Essential oil is reported to exhibit pharmacological properties, besides its common and well-known function as aromatherapy. Therefore, this study herein aimed to investigate the anti-proliferative effect of essential oil extracted from leaves of Garcinia atroviridis (EO-L) against PANC-1 human pancreatic cancer cell line. The cell growth inhibitory concentration at 50% (IC50) and selective index (SI) values of EO-L analyses were determined as 78 µg/mL and 1.23, respectively. Combination index (CI) analysis revealed moderate synergism (CI values of 0.36 to 0.75) between EO-L and 2 deoxy-d-glucose (2-DG) treatments. The treatments of PANC-1 cells with EO-L, 2-DG and EOL+2DG showed evidence of depolarization of mitochondrial membrane potential, cell growth arrest and apoptosis. The molecular mechanism causing the anti-proliferative effect between EO-L and 2-DG is potentially through pronounced up-regulation of P53 (4.40-fold), HIF1α (1.92-fold), HK2 (2.88-fold) and down-regulation of CYP3A5 (0.11-fold), as supported by quantitative mRNA expression analysis. Collectively, the current data suggest that the combination of two anti-proliferative agents, EO-L and 2-DG, can potentially be explored as therapeutic treatments and as potentiating agents to conventional therapy against human pancreatic cancer.
    Matched MeSH terms: Pancreatic Neoplasms/drug therapy*
  19. A Review on Biological Properties and Synthetic Methodologies of Diarylpentadienones
    Abdullah MA, Mohd Faudzi SM, Nasir NM
    Mini Rev Med Chem, 2021;21(9):1058-1070.
    PMID: 33272171 DOI: 10.2174/1389557520999201203213957
    Medicinal chemists have continuously shown interest in new curcuminoid derivatives, diarylpentadienones, owing to their enhanced stability feature and easy preparation using a one-pot synthesis. Thus far, methods such as Claisen-Schmidt condensation and Julia- Kocienski olefination have been utilised for the synthesis of these compounds. Diarylpentadienones possess a high potential as a chemical source for designing and developing new and effective drugs for the treatment of diseases, including inflammation, cancer, and malaria. In brief, this review article focuses on the broad pharmacological applications and the summary of the structure-activity relationship of molecules, which can be employed to further explore the structure of diarylpentadienone. The current methodological developments towards the synthesis of diarylpentadienones are also discussed.
    Matched MeSH terms: Neoplasms/drug therapy*
  20. Doxorubicin-loaded micelles of amphiphilic diblock copolymer with pendant dendron improve antitumor efficacy: In vitro and in vivo studies
    Voon SH, Kue CS, Imae T, Saw WS, Lee HB, Kiew LV, et al.
    Int J Pharm, 2017 Dec 20;534(1-2):136-143.
    PMID: 29031979 DOI: 10.1016/j.ijpharm.2017.10.023
    Previously reported amphiphilic diblock copolymer with pendant dendron moieties (P71D3) has been further evaluated in tumor-bearing mice as a potential drug carrier. This P71D3-based micelle of an average diameter of 100nm was found to be biocompatible, non-toxic and physically stable in colloidal system up to 15days. It enhanced the in vitro potency of doxorubicin (DOX) in 4T1 breast tumor cells by increasing its uptake, by 3-fold, compared to free DOX. In 4T1 tumor-bearing mice, the tumor growth rate of P71D3/DOX (2mg/kg DOX equivalent) treated group was significantly delayed and their tumor volume was significantly reduced by 1.5-fold compared to those treated with free DOX. The biodistribution studies indicated that P71D3/DOX enhanced accumulation of DOX in tumor by 5- and 2-fold higher than free DOX treated mice at 15min and 1h post-administration, respectively. These results suggest that P71D3 micelle is a promising nanocarrier for chemotherapeutic agents.
    Matched MeSH terms: Breast Neoplasms/drug therapy
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