Displaying publications 21 - 40 of 102 in total

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  1. Polymer-albumin conjugate for the facilitated delivery of macromolecular platinum drugs
    Dag A, Jiang Y, Karim KJ, Hart-Smith G, Scarano W, Stenzel MH
    Macromol Rapid Commun, 2015 May;36(10):890-7.
    PMID: 25790077 DOI: 10.1002/marc.201400576
    The delivery of macromolecular platinum drugs into cancerous cells is enhanced by conjugating the polymer to albumin. The monomers N-(2-hydroxypropyl)methacrylamide (HPMA) and Boc protected 1,3-diaminopropan-2-yl acrylate (Ac-DAP-Boc) are copolymerized in the presence of a furan protected maleimide functionalized reversible addition-fragmentation chain transfer (RAFT) agent. The resulting polymer with a composition of P(HPMA14 -co-(Ac-DAP-Boc)9 ) and a molecular weight of Mn = 7600 g mol(-1) (Đ = 1.24) is used as a macromolecular ligand for the conjugation to the platinum drug. Thermogravimetric analysis reveals full conjugation. After deprotection of the maleimide functionality of the polymer, the reactive polymer is conjugated to albumin using the Cys34 functionality. The conjugation is monitored using size exclusion chromatography, MALDI-TOF (matrix assisted laser desorption ionization time-of-flight), and SDS Page (sodium dodecyl sulphate polyacrylamide gel electrophoresis). The polymer-albumin conjugates self-assemble in water into nanoparticles of sizes of around 80 nm thanks to the hydrophobic nature of the platinum drugs. The albumin coated nanoparticles are readily taken up by ovarian cancer cell lines and they show superior toxicity compared to a control sample without protein coating.
    Matched MeSH terms: Cisplatin/pharmacology*; Cisplatin/chemistry
  2. [Zn(phen)(O,N,O)(H2O)] and [Zn(phen)(O,N)(H2O)] with O,N,O is 2,6-dipicolinate and N,O is L-threoninate: synthesis, characterization, and biomedical properties
    Chin LF, Kong SM, Seng HL, Tiong YL, Neo KE, Maah MJ, et al.
    J Biol Inorg Chem, 2012 Oct;17(7):1093-105.
    PMID: 22825726 DOI: 10.1007/s00775-012-0923-y
    Two ternary Zn(II) complexes, with 1,10-phenanthroline (phen) as the main ligand and a carboxylate-containing ligand [dipicolinate (dipico) or L-threoninate (L-Thr)] as the subsidiary ligand, were prepared and characterized by elemental analysis, Fourier transform IR, UV, and fluorescence spectroscopy, X-ray diffraction, molar conductivity, and electrospray ionization mass spectrometry. X-ray structure analysis shows that both [Zn(phen)(dipico)(H(2)O)]·H(2)O (1) and [Zn(phen)(L-Thr)(H(2)O)Cl]·2H(2)O (2) have octahedral geometry about the Zn(II) atom. Both complexes can inhibit topoisomerase I, and have better anticancer activity than cisplatin against nasopharyngeal cancer cell lines, HK1 and HONE-1, with concentrations causing 50 % inhibition of cell proliferation (IC(50)) in the low micromolar range. Complex 2 has the highest therapeutic index for HK1. Both Zn(II) complexes can induce cell death by apoptosis. Changing the subsidiary ligand in the Zn(II) complexes affects the UV-fluorescence spectral properties of the coordinated phen ligand, the binding affinity for some DNA sequences, nucleobase sequence-selective binding, the phase at which cell cycle progression was arrested for treated cancer cells, and their therapeutic index.
    Matched MeSH terms: Cisplatin/pharmacology; Cisplatin/chemistry
  3. Fulltext Radiosensitization Effects by Bismuth Oxide Nanoparticles in Combination with Cisplatin for High Dose Rate Brachytherapy
    Sisin NNT, Abdul Razak K, Zainal Abidin S, Che Mat NF, Abdullah R, Ab Rashid R, et al.
    Int J Nanomedicine, 2019;14:9941-9954.
    PMID: 31908451 DOI: 10.2147/IJN.S228919
    Purpose: The aim of this study was to investigate the potential of the synergetic triple therapeutic combination encompassing bismuth oxide nanoparticles (BiONPs), cisplatin (Cis), and high dose rate (HDR) brachytherapy with Ir-192 source in breast cancer and normal fibroblast cell line.

    Methods: In vitro models of breast cancer cell lines (MCF-7, MDA-MB-231) and normal fibroblast cell line (NIH/3T3) were employed. Cellular localization and cytotoxicity studies were conducted prior to inspection on the radiosensitization effects and generation of reactive oxygen species (ROS) on three proposed radiosensitizers: BiONPs, Cis, and BiONPs-Cis combination (BC). The optimal, non-cytotoxic concentration of BiONPs (0.5 mM) and the 25% inhibitory concentration of Cis (1.30 µM) were applied. The radiosensitization effects were evaluated by using a 0.38 MeV Iridium-192 HDR brachytherapy source over a prescribed dose range of 0 Gy to 4 Gy.

    Results: The cellular localization of BiONPs was visualized by light microscopy and accumulation of the BiONPs within the vicinity of the nuclear membrane was observed. Quantification of the sensitization enhancement ratio extrapolated from the survival curves indicates radiosensitization effects for MCF-7 and MDA-MB-231 when treated with BiONPs, Cis, and BC. However, NIH/3T3 cells exhibited contradictive behavior as it only reacted towards the BC combination. Nonetheless, the MCF-7 cell line loaded with BC shows the highest SER of 4.29. ROS production analysis, on the other hand, shows that Cis and BC radiosensitizers generated the highest free radicals in comparison to BiONPs alone.

    Conclusion: A BiONPs-Cis combination was unveiled as a novel approach that offers promising radiosensitization enhancement that will increase the efficiency of tumor control while preserving the normal tissue at a reduced dose. This data is the first precedent to prove the synergetic implication of BiONPs, Cis, and HDR brachytherapy that will be beneficial for future chemoradiotherapy strategies in cancer care.

    Matched MeSH terms: Cisplatin/administration & dosage; Cisplatin/pharmacology*
  4. Fulltext Aberrant expression of the S1P regulating enzymes, SPHK1 and SGPL1, contributes to a migratory phenotype in OSCC mediated through S1PR2
    Patmanathan SN, Johnson SP, Lai SL, Panja Bernam S, Lopes V, Wei W, et al.
    Sci Rep, 2016 05 10;6:25650.
    PMID: 27160553 DOI: 10.1038/srep25650
    Oral squamous cell carcinoma (OSCC) is a lethal disease with a 5-year mortality rate of around 50%. Molecular targeted therapies are not in routine use and novel therapeutic targets are required. Our previous microarray data indicated sphingosine 1-phosphate (S1P) metabolism and signalling was deregulated in OSCC. In this study, we have investigated the contribution of S1P signalling to the pathogenesis of OSCC. We show that the expression of the two major enzymes that regulate S1P levels were altered in OSCC: SPHK1 was significantly upregulated in OSCC tissues compared to normal oral mucosa and low levels of SGPL1 mRNA correlated with a worse overall survival. In in vitro studies, S1P enhanced the migration/invasion of OSCC cells and attenuated cisplatin-induced death. We also demonstrate that S1P receptor expression is deregulated in primary OSCCs and that S1PR2 is over-expressed in a subset of tumours, which in part mediates S1P-induced migration of OSCC cells. Lastly, we demonstrate that FTY720 induced significantly more apoptosis in OSCC cells compared to non-malignant cells and that FTY720 acted synergistically with cisplatin to induce cell death. Taken together, our data show that S1P signalling promotes tumour aggressiveness in OSCC and identify S1P signalling as a potential therapeutic target.
    Matched MeSH terms: Cisplatin
  5. Fulltext Cisplatin-Resistance in Oral Squamous Cell Carcinoma: Regulation by Tumor Cell-Derived Extracellular Vesicles
    Khoo XH, Paterson IC, Goh BH, Lee WL
    Cancers (Basel), 2019 Aug 14;11(8).
    PMID: 31416147 DOI: 10.3390/cancers11081166
    Drug resistance remains a severe problem in most chemotherapy regimes. Recently, it has been suggested that cancer cell-derived extracellular vesicles (EVs) could mediate drug resistance. In this study, the role of EVs in mediating the response of oral squamous cell carcinoma (OSCC) cells to cisplatin was investigated. We isolated and characterized EVs from OSCC cell lines showing differential sensitivities to cisplatin. Increased EV production was observed in both de novo (H314) and adaptive (H103/cisD2) resistant lines compared to sensitive H103 cells. The protein profiles of these EVs were then analyzed. Differences in the proteome of EVs secreted by H103 and H103/cisD2 indicated that adaptation to cisplatin treatment caused significant changes in the secreted nanovesicles. Intriguingly, both resistant H103/cisD2 and H314 cells shared a highly similar EV protein profile including downregulation of the metal ion transporter, ATP1B3, in the EVs implicating altered drug delivery. ICP-MS analysis revealed that less cisplatin accumulated in the resistant cells, but higher levels were detected in their EVs. Therefore, we inhibited EV secretion from the cells using a proton pump inhibitor and observed an increased drug sensitivity in cisplatin-resistant H314 cells. This finding suggests that control of EV secretion could be a potential strategy to enhance the efficacy of cancer treatment.
    Matched MeSH terms: Cisplatin
  6. Fulltext Phytochemicals and Cytotoxicity of Quercus infectoria Ethyl Acetate Extracts on Human Cancer Cells
    Yusof WNSW, Abdullah H
    Trop Life Sci Res, 2020 Apr;31(1):69-84.
    PMID: 32963712 DOI: 10.21315/tlsr2020.31.1.5
    Conventional and modern cancer treatment were reported to manifest adverse effects to the patients. More researches were conducted to search for selective cytotoxic agent of plant natural product on cancer cells. The presences of wide range phytochemicals in Quercus infectoria (QI) extract have been implicated with the cytotoxic effect against various types of cancer cell which remain undiscovered. This present study aimed to evaluate cytotoxic effect of QI extracts on selected human cancer cells and then, the most potent extract was further analysed for general phytochemical constituents. QI galls were extracted successively with n-hexane, ethyl acetate and methanol yielded three main extracts; n-hexane (QIH), ethyl acetate (QIEA) and methanol (QIM), respectively. The most potent extract was qualitatively analysed for the present of tannin, alkaloids, glycosides, saponins, terpenoids, flavonoids and phenolic compounds. Next, the extracts were tested to determine the cytotoxic activity against cervical cancer cells (HeLa), breast cancer cells (MDA-MB-231) and liver cancer cells (Hep G2) using MTT assay. Cytotoxic activity of QI extracts against normal fibroblast (L929) cell line was also evaluated to determine the cytoselective property. Meanwhile, DMSO-treated cells served as negative control while cisplatin-treated cells served as positive control. The most potent extract then chosen to be further investigated for DNA fragmentation as hallmark of apoptosis using Hoechst staining. Qualitative phytochemical analysis revealed the presence of tannin, alkaloids, glycosides, saponins, terpenoids, flavonoids and phenolic compounds. QIEA extract exhibited the most potent cytotoxic activity against HeLa cells with (IC50 value = 6.33 ± 0.33 μg/mL) and showed cytoselective property against L929 cells. DNA fragmentation revealed QIEA induced apoptosis in the treated cells. The richness of phytochemical constituents in QIEA extract might contribute to the potency of cytotoxic activity towards HeLa cells.
    Matched MeSH terms: Cisplatin
  7. In vitro and in vivo evaluation of drug-eluting microspheres designed for transarterial chemoembolization therapy
    Wang Y, Molin DG, Sevrin C, Grandfils C, van den Akker NM, Gagliardi M, et al.
    Int J Pharm, 2016 Apr 30;503(1-2):150-62.
    PMID: 26965198 DOI: 10.1016/j.ijpharm.2016.03.002
    Poly(d,l-lactic acid) biodegradable microspheres, loaded with the drugs cisplatin and/or sorafenib tosylate, were prepared, characterized and studied. Degradation of the microspheres, and release of cisplatin and/or sorafenib tosylate from them, were investigated in detail. Incubation of the drug-carrying microspheres in phosphate buffered saline (pH=7.4) revealed slow degradation. Nevertheless, significant release of cisplatin and sorafenib tosylate from microspheres loaded with both drugs was apparent in vitro; this can be attributed to their porous structure. Supernatants from microspheres loaded with both drugs showed strong toxic effects on cells (i.e. endothelial cells, fibroblast cells and Renca tumor cells) and potent anti-angiogenic effect in the matrigel endothelial tube assay. In vivo anti-tumor effects of the microspheres were also observed, in a Renca tumor mouse model. The poly(d,l-lactic acid) microspheres containing both cisplatin and sorafenib tosylate revealed highest therapeutic efficacy, probably demonstrating that combined local administration of cisplatin and sorafenib tosylate synergistically inhibits tumor growth in situ. In conclusion, this study demonstrates the applicability of biodegradable poly(d,l-lactic acid) microspheres loaded with cisplatin and sorafenib tosylate for local drug delivery as well as the potential of these microspheres for future use in transarterial chemoembolization.
    Matched MeSH terms: Cisplatin
  8. Fulltext Intraperitoneal chemotherapy following refractory intravenous route in advanced ovarian cancer
    Shafiee, M.N., Omar, M.H., Suraya, A., Hatta, M.
    Journal of Surgical Academia, 2013;3(1):28-31.
    MyJurnal
    Platinum based adjuvant chemotherapy is generally recommended for ovarian cancer to improve the survival rate. Intravenous route is commonly used, easily administered and less associated complications. However, intraperitoneal route is gaining its popularity as a single procedure or adjunctive to the intravenous route. Numerous questions on its eligibility and safety are still perplexed. A case review on a patient with non optimal debulking surgery of advanced ovarian cancer was studied. Intravenous platinum based chemotherapy combined with paclitaxel failed to bring her to clinical remission. Second line chemotherapy, gemcitabin rendered her to poor response with unresolved debilitating ascites needing recurrent drainage. Surprisingly, a trial of intraperitoneal chemotherapy with cisplatin revealed a great response with a complete clinical remission.
    Matched MeSH terms: Cisplatin
  9. Fulltext Extra-gonadal germ cell tumour – what about the testis!
    Johann, F.K., Praveen, S., Christopher, C.K.H., Goh, E.H., Razman, J., Zulkifli, M.Z.
    Journal of Surgical Academia, 2011;1(1):28-31.
    MyJurnal
    Extra-gonadal germ cell tumours (EGGCT) are rare. Therefore further investigations of the testis is aimed at sourcing a possible primary origin of gonadal tumour. Over the years, various case series on EGGCT have been reported questioning its true nature as in a majority of them, a primary source is found in the testis, thus representing a metastatic gonadal tumour. The testis pathology could be either a true germ cell foci, an intra-tubular epithelial neoplasia or an area of fibrosis, indicating a ‘burnt out tumour’. We report a 39-year-old male who underwent laparotomy and excision of a retroperitoneal tumour. Histopathological examination revealed retroperitoneal lymph node of mixed germ cell tumour origin. Clinical and ultrasound examination of bilateral testis was normal. The patient refused orchidectomy or a testicular biopsy. He underwent four cycles of bleomycin, cisplatin, and etoposide with no evidence of tumour recurrence on follow up and remains disease free after 12 months of diagnosis. A literature review of EGGCT, its relation and factors relating with future testicular tumour is presented.
    Matched MeSH terms: Cisplatin
  10. Fulltext Suppression of Cisplatin-Induced Vomiting byCannabis sativain Pigeons: Neurochemical Evidences
    Ullah I, Subhan F, Alam J, Shahid M, Ayaz M
    Front Pharmacol, 2018;9:231.
    PMID: 29615907 DOI: 10.3389/fphar.2018.00231
    Cannabis sativa
    (CS, familyCannabinaceae) has been reported for its anti-emetic activity against cancer chemotherapy-induced emesis in animal models and in clinics. The current study was designed to investigateCSfor potential effectiveness to attenuate cisplatin-induced vomiting in healthy pigeons and to study the impact on neurotransmitters involved centrally and peripherally in the act of vomiting. High-performance liquid chromatography system coupled with electrochemical detector was used for the quantification of neurotransmitters 5-hydroxytryptamine (5HT), dopamine (DA) and their metabolites; Di-hydroxy Phenyl Acetic acid (Dopac), Homovanillic acid (HVA), and 5-hydroxy indole acetic acid (5HIAA) centrally in specific brain areas (area postrema and brain stem) while, peripherally in small intestine. Cisplatin (7 mg/kg i.v.) induce emesis without lethality across the 24 h observation period.CShexane fraction (CS-HexFr; 10 mg/kg) attenuated cisplatin-induced emesis ∼ 65.85% (P< 0.05); the reference anti-emetic drug, metoclopramide (MCP; 30 mg/kg), produced ∼43.90% reduction (P< 0.05). At acute time point (3rdh), CS-HexFr decreased (P< 0.001) the concentration of 5HT and 5HIAA in the area postrema, brain stem and intestine, while at 18thh (delayed time point) CS-HexFr attenuated (P< 0.001) the upsurge of 5HT caused by cisplatin in the brain stem and intestine and dopamine in the area postrema.CS-HexFr treatment alone did not alter the basal neurotransmitters and their metabolites in the brain areas and intestine except 5HIAA and HVA, which were decreased significantly. In conclusion the anti-emetic effect ofCS-HexFr is mediated by anti-serotonergic and anti-dopaminergic components in a blended manner at the two different time points, i.e., 3rdand 18thh in pigeons.
    Matched MeSH terms: Cisplatin
  11. Fulltext Vestibulotoxicity Associated With Platinum-Based Chemotherapy in Survivors of Cancer: A Scoping Review
    Prayuenyong P, Taylor JA, Pearson SE, Gomez R, Patel PM, Hall DA, et al.
    Front Oncol, 2018;8:363.
    PMID: 30319960 DOI: 10.3389/fonc.2018.00363
    Background: Cochleotoxicity following the treatment with platinum-based chemotherapy is well documented. The potential for vestibulotoxicity is still unclear. This scoping review examined the extent of current research literature, summarized research findings and identified research gaps regarding vestibular-related adverse effects associated with platinum-based chemotherapy in survivors of cancer. Methods: Inclusion criteria followed the PICO principles: Participants, adult, and pediatric cancer patients of any cancer type; Intervention, platinum-based chemotherapy (such as cisplatin, carboplatin, and oxaliplatin); Control, none or any; Outcomes, vestibular-related adverse effects. English language articles published since 1978 were retrieved. Seventy-five eligible studies were identified from a systematic literature search, and relevant data were charted, collated, and summarized. Results: Testing for vestibulotoxicity predominately featured functional evaluation of the horizontal semicircular canal using the caloric and rotational tests. The rate of abnormal vestibular function test results after chemotherapy administration varied from 0 to 50%. The results of objective testing did not always correspond to patient symptoms. There is tentative support for patients with pre-existing loss of vestibular function to be more likely to experience vestibular toxicity after dosing with cisplatin. Conclusions: A number of studies reported significant evidence of vestibular toxicities associated with platinum-based chemotherapy, especially cisplatin. This scoping review emphasizes that vestibular toxicity needs more attention and comprehensive evaluation. Specifically, studies that analyse cumulative dose of platinum-based chemotherapy, affected sites of lesion in vestibular end organs, and the correlation and temporal patterns of cochlear and vestibular toxicity are needed.
    Matched MeSH terms: Cisplatin
  12. Inhibition of nasopharyngeal carcinoma cell proliferation and synergism of cisplatin with silvestrol and episilvestrol isolated from Aglaia stellatopilosa
    Daker M, Yeo JT, Bakar N, Abdul Rahman AS, Ahmad M, Yeo TC, et al.
    Exp Ther Med, 2016 Jun;11(6):2117-2126.
    PMID: 27284293
    Nasopharyngeal carcinoma (NPC) is a type of tumour that arises from the epithelial cells that line the surface of the nasopharynx. NPC is treated with radiotherapy and cytotoxic chemotherapeutic drugs such as cisplatin and 5-fluorouracil. However, current strategies are often associated with potential toxicities. This has prompted efforts to identify alternative methods of treatment. The present study aimed to investigate silvestrol and episilvestrol-mediated inhibition of cell proliferation in human NPC cells. The growth kinetics of NPC cells treated with silvestrol or episilvestrol were monitored dynamically using a real-time, impedance-based cell analyzer, and dose-response profiles were generated using a colorimetric cell viability assay. Furthermore, apoptosis was evaluated using flow cytometry and high content analysis. In addition, flow cytometry was performed to determine cell cycle distribution. Finally, the effects of combining silvestrol or episilvestrol with cisplatin on NPC cells was examined. Apoptosis was not observed in silvestrol and episilvestrol-treated NPC cells, although cell cycle perturbation was evident. Treatment with both compounds induced a significant increase in the percentage of cells in the G2/M phase, as compared with the control. In vitro cultures combining silvestrol or episilvestrol with cisplatin showed synergistic effects against NPC cells. The results of the present study suggested that silvestrol and episilvestrol had an anti-tumour activity in NPC cells. Silvestrol and episilvestrol, particularly in combination with cisplatin, merit further investigation, so as to determine the cellular mechanisms underlying their action(s) as anti-NPC agents.
    Matched MeSH terms: Cisplatin
  13. Renal denervation restores the baroreflex control of renal sympathetic nerve activity and heart rate in Wistar-Kyoto rats with cisplatin-induced renal failure
    Khan SA, Sattar MA, Rathore HA, Abdulla MH, Ud Din Ahmad F, Ahmad A, et al.
    Acta Physiol (Oxf), 2014 Mar;210(3):690-700.
    PMID: 24438102 DOI: 10.1111/apha.12237
    There is evidence that in chronic renal failure, the sympathetic nervous system is activated. This study investigated the role of the renal innervation in suppressing high- and low-pressure baroreflex control of renal sympathetic nerve activity and heart rate in cisplatin-induced renal failure.
    Matched MeSH terms: Cisplatin/toxicity
  14. Fulltext Pulchrin A, a New Natural Coumarin Derivative of Enicosanthellum pulchrum, Induces Apoptosis in Ovarian Cancer Cells via Intrinsic Pathway
    Nordin N, Fadaeinasab M, Mohan S, Mohd Hashim N, Othman R, Karimian H, et al.
    PLoS One, 2016;11(5):e0154023.
    PMID: 27136097 DOI: 10.1371/journal.pone.0154023
    Drug resistance presents a challenge in chemotherapy and has attracted research interest worldwide and particular attention has been given to natural compounds to overcome this difficulty. Pulchrin A, a new compound isolated from natural products has demonstrated novel potential for development as a drug. The identification of pulchrin A was conducted using several spectroscopic techniques such as nuclear magnetic resonance, liquid chromatography mass spectrometer, infrared and ultraviolet spectrometry. The cytotoxicity effects on CAOV-3 cells indicates that pulchrin A is more active than cisplatin, which has an IC50 of 22.3 μM. Significant changes in cell morphology were present, such as cell membrane blebbing and formation of apoptotic bodies. The involvement of phosphatidylserine (PS) in apoptosis was confirmed by Annexin V-FITC after a 24 h treatment. Apoptosis was activated through the intrinsic pathway by activation of procaspases 3 and 9 as well as cleaved caspases 3 and 9 and ended at the executioner pathway, with the occurrence of DNA laddering. Apoptosis was further confirmed via gene and protein expression levels, in which Bcl-2 protein was down-regulated and Bax protein was up-regulated. Furthermore, the CAOV-3 cell cycle was disrupted at the G0/G1 phase, leading to apoptosis. Molecular modeling of Bcl-2 proteins demonstrated a high- binding affinity, which inhibited the function of Bcl-2 proteins and led to cell death. Results of the current study can shed light on the development of new therapeutic agents, particularly, human ovarian cancer treatments.
    Matched MeSH terms: Cisplatin/pharmacology
  15. Beware the undescended testis and abdominal mass
    Koh KB
    Aust N Z J Surg, 1996 Dec;66(12):851-3.
    PMID: 8996073
    We report five patients who presented with seminoma of an undescended testis to highlight the importance of dealing with adult cryptorchidism. On the basis of the literature review and our experience, we advocate orchidectomy for post-pubertal cryptorchid patients of any age because follow-up may be difficult, and treatment for the tumour may be unsuccessful.
    Matched MeSH terms: Cisplatin/administration & dosage
  16. Adverse effects of cytotoxics-platinum agents
    Selvaratnam G, Philips RH, Mohamed AK, Radzi A
    Adverse Drug React Toxicol Rev, 1997 Aug;16(3):171-97.
    PMID: 9512763
    Matched MeSH terms: Cisplatin/adverse effects*
  17. Fulltext Ondansetron against metoclopramide/dexamethasone--a comparative study
    Lim AKH, Haron MR, Yap TM
    Med J Malaysia, 1994 Sep;49(3):231-8.
    PMID: 7845271
    This trial was carried out in Hospital Kuala Lumpur. Fifty-two patients who were scheduled to receive their first or subsequent courses of cancer chemotherapy with single dose cisplatinum containing chemotherapy regimens were evaluated. Thirty-four patients were given ondansetron in one group while 18 in the other group received metoclopramide with dexamethasone. The response to treatment was categorised as complete (0 emetic episode), major (1 or 2 emetic episodes), minor (3 to 5 emetic episodes) or failure (> 5 emetic episodes or rescue medication). Among the 52 patients, a complete or major control (0 to 2 emetic episodes) was achieved in 23/34 patients (68%) from the ondansetron group and in 3/18 patients (17%) from the metoclopramide with dexamethasone group (p < 0.002) on day 1. Similarly, the control of nausea was greater in the ondansetron group compared with the metoclopramide with dexamethasone group (p < 0.0009) on day 1. Two patients were excluded (dropped out) after day one from each of the two study groups due to excessive vomiting subsequent to cisplatinum therapy. From days 2 to 6, there was a trend in favour of ondansetron. Both treatments were well tolerated. The results of this trial show that in the prophylaxis of nausea and vomiting induced by cisplatinum containing chemotherapy, the efficacy of ondansetron is superior to that of a standard anti-emetic combination, metoclopramide with dexamethasone.
    Matched MeSH terms: Cisplatin/adverse effects*
  18. Adjuvant cytotoxic chemotherapy following Wertheim radical hysterectomy for cervical cancer
    Sivanesaratnam V, Sen DK, Jayalakshmi P
    Aust N Z J Obstet Gynaecol, 1987 Aug;27(3):231-3.
    PMID: 2449159
    Patients at high risk of recurrence or metastases following radical surgery for Stage 1B and 2A cervical carcinoma include those with pelvic node metastases, lymphatic or vascular space permeation in the cervix by tumour cells, large size of the primary tumour, involvement of the full thickness of the cervix and parametrial spread. We report the initial results of adjuvant chemotherapy using a combination of cisplatinum, bleomycin and vinblastine in 22 patients who had undergone Wertheim radical hysterectomy and were thought to be at high risk of developing recurrence. The mean duration of follow-up was 23 months. All are alive after follow-up ranging from 13 to 43 months. Three patients developed recurrences--one in the pelvis, another at the posterior aspect of the urethral meatus and the third developed pulmonary secondaries at 20 to 23 months after surgery. Toxicity from the chemotherapy was acceptable.
    Matched MeSH terms: Cisplatin/administration & dosage
  19. Fulltext Synergetic Influence of Bismuth Oxide Nanoparticles, Cisplatin and Baicalein-Rich Fraction on Reactive Oxygen Species Generation and Radiosensitization Effects for Clinical Radiotherapy Beams
    Talik Sisin NN, Abdul Razak K, Zainal Abidin S, Che Mat NF, Abdullah R, Ab Rashid R, et al.
    Int J Nanomedicine, 2020;15:7805-7823.
    PMID: 33116502 DOI: 10.2147/IJN.S269214
    Purpose: This study aimed to quantify synergetic effects induced by bismuth oxide nanoparticles (BiONPs), cisplatin (Cis) and baicalein-rich fraction (BRF) natural-based agent on the reactive oxygen species (ROS) generation and radiosensitization effects under irradiation of clinical radiotherapy beams of photon, electron and HDR-brachytherapy. The combined therapeutic responses of each compound and clinical radiotherapy beam were evaluated on breast cancer and normal fibroblast cell line.

    Methods: In this study, individual BiONPs, Cis, and BRF, as well as combinations of BiONPs-Cis (BC), BiONPs-BRF (BB) and BiONPs-Cis-BRF (BCB) were treated to the cells before irradiation using HDR brachytherapy with 0.38 MeV iridium-192 source, 6 MV photon beam and 6 MeV electron beam. The individual or synergetic effects from the application of the treatment components during the radiotherapy were elucidated by quantifying the ROS generation and radiosensitization effects on MCF-7 and MDA-MB-231 breast cancer cell lines as well as NIH/3T3 normal cell line.

    Results: The ROS generated in the presence of Cis stimulated the most substantial amount of ROS compared to the BiONPs and BRF. Meanwhile, the combination of the components had induced the higher ROS levels for photon beam than the brachytherapy and electron beam. The highest ROS enhancement relative to the control is attributable to the presence of BC combination in MDA-MB-231 cells, in comparison to the BB and BCB combinations. The radiosensitization effects which were quantified using the sensitization enhancement ratio (SER) indicate the highest value by BC in MCF-7 cells, followed by BCB and BB treatment. The radiosensitization effects are found to be more prominent for brachytherapy in comparison to photon and electron beam.

    Conclusion: The BiONPs, Cis and BRF are the potential radiosensitizers that could improve the efficiency of radiotherapy to eradicate the cancer cells. The combination of these potent radiosensitizers might produce multiple effects when applied in radiotherapy. The BC combination is found to have the highest SER, followed by the BCB combination. This study is also the first to investigate the effect of BRF in combination with BiONPs (BB) and BC (BCB) treatments.

    Matched MeSH terms: Cisplatin/pharmacology*
  20. Over-expression of MAGED4B increases cell migration and growth in oral squamous cell carcinoma and is associated with poor disease outcome
    Chong CE, Lim KP, Gan CP, Marsh CA, Zain RB, Abraham MT, et al.
    Cancer Lett, 2012 Aug 1;321(1):18-26.
    PMID: 22459352 DOI: 10.1016/j.canlet.2012.03.025
    MAGE proteins have been shown to be good targets for cancer immunotherapy. We demonstrate that MAGED4B is over-expressed in more than 50% of Oral Squamous Cell Carcinoma (OSCC) tissues and the expression of MAGED4B is associated with lymph node metastasis and poor disease specific survival. OSCC cell lines that over-express MAGED4B promote migration in vitro, exhibit an increase in cell growth both in vitro and in vivo, and are more resistant to apoptosis compared to control cells. Our data suggest that MAGED4B over-expression is a driver in oral carcinogenesis and argues strongly that this protein may represent a potential therapeutic target in OSCC.
    Matched MeSH terms: Cisplatin/therapeutic use
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