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  1. A Comparative Study of Cellular Uptake and Subcellular Localization of Doxorubicin Loaded in Self-Assemblies of Amphiphilic Copolymers with Pendant Dendron by MDA-MB-231 Human Breast Cancer Cells
    Viswanathan G, Hsu YH, Voon SH, Imae T, Siriviriyanun A, Lee HB, et al.
    Macromol Biosci, 2016 06;16(6):882-95.
    PMID: 26900760 DOI: 10.1002/mabi.201500435
    Previously synthesized amphiphilic diblock copolymers with pendant dendron moieties have been investigated for their potential use as drug carriers to improve the delivery of an anticancer drug to human breast cancer cells. Diblock copolymer (P71 D3 )-based micelles effectively encapsulate the doxorubicin (DOX) with a high drug-loading capacity (≈95%, 104 DOX molecules per micelle), which is approximately double the amount of drug loaded into the diblock copolymer (P296 D1 ) vesicles. DOX released from the resultant P71 D3 /DOX micelles is approximately 1.3-fold more abundant, at a tumoral acidic pH of 5.5 compared with a pH of 7.4. The P71 D3 /DOX micelles also enhance drug potency in breast cancer MDA-MB-231 cells due to their higher intracellular uptake, by approximately twofold, compared with the vesicular nanocarrier, and free DOX. Micellar nanocarriers are taken up by lysosomes via energy-dependent processes, followed by the release of DOX into the cytoplasm and subsequent translocation into the nucleus, where it exert its cytotoxic effect.
    Matched MeSH terms: Doxorubicin/administration & dosage*
  2. Fulltext A pH-sensitive, biobased calcium carbonate aragonite nanocrystal as a novel anticancer delivery system
    Shafiu Kamba A, Ismail M, Tengku Ibrahim TA, Zakaria ZA
    Biomed Res Int, 2013;2013:587451.
    PMID: 24324966 DOI: 10.1155/2013/587451
    The synthesised biobased calcium carbonate nanocrystals had demonstrated to be an effective carrier for delivery of anticancer drug doxorubicin (DOX). The use of these nanocrystals displayed high levels of selectivity and specificity in achieving effective cancer cell death without nonspecific toxicity. These results confirmed that DOX was intercalated into calcium carbonate nanocrystals at high loading and encapsulation efficiency (4.8 and 96%, resp.). The CaCO₃/DOX nanocrystals are relatively stable at neutral pH (7.4), resulting in slow release, but the nanocrystals progressively dissociated in acidic pH (4.8) regimes, triggering faster release of DOX. The CaCO₃/DOX nanocrystals exhibited high uptake by MDA MB231 breast cancer cells and a promising potential delivery of DOX to target cells. In vitro chemosensitivity using MTT, modified neutral red/trypan blue assay, and LDH on MDA MB231 breast cancer cells revealed that CaCO₃/DOX nanocrystals are more sensitive and gave a greater reduction in cell growth than free DOX. Our findings suggest that CaCO₃ nanocrystals hold tremendous promise in the areas of controlled drug delivery and targeted cancer therapy.
    Matched MeSH terms: Doxorubicin/administration & dosage*
  3. Fulltext Combination chemotherapy for small cell lung cancer
    Sufarlan AW, Zainudin BM
    Med J Malaysia, 1993 Jun;48(2):166-70.
    PMID: 8394502
    Small cell lung cancer (SCLC) disseminates early and has poor prognosis. However, SCLC is highly chemosensitive, thus chemotherapy has been established as the primary mode of treatment. Seventeen patients (15 males and 2 females) with median age of 60 years (range 49 to 74 years) were treated with combination cyclophosphamide 750 mg/m2, adriamycin 40 mg/m2, vincristine 1.4 mg/m2 on day 1 and etoposide (VP 16) 75 mg/m2 on days 1 to 3 (CAVE). This combination was given in 6 courses at 3 weekly intervals. The response to the chemotherapy and the quality of life of patients was assessed at the third cycle and after the completion of therapy (sixth cycle). The overall response rate was 76.4%; 52.9% achieved complete response and 23.5% had partial response. The survival rate at 6 months was 70.8% and 4 patients (23.5%) were still alive after 1 year of chemotherapy. The median survival after therapy was 36 weeks. There was a 30% overall improvement in the Karnofsky performance score at the completion of chemotherapy. This study illustrated that the CAVE regimen is effective and beneficial in the majority of our patients with small cell lung cancer.
    Matched MeSH terms: Doxorubicin/administration & dosage
  4. Fulltext Comparison of doxorubicin anticancer drug loading on different metal oxide nanoparticles
    Javed KR, Ahmad M, Ali S, Butt MZ, Nafees M, Butt AR, et al.
    Medicine (Baltimore), 2015 Mar;94(11):e617.
    PMID: 25789952 DOI: 10.1097/MD.0000000000000617
    Nanomaterials are being vigorously investigated for their use in anticancer drug delivery regimes or as biomarkers agents and are considered to be a candidate to provide a way to combat severe weaknesses of anticancer drug pharmacokinetics, such as their nonspecificity. Because of this weakness, a bigger proportion of the drug-loaded nanomaterials flow toward healthy tissues and result in undesirable side effects. It is very important to evaluate drug loading and release efficiency of various nanomaterials to find out true pharmacokinetics of these drugs.This observational study aims to evaluate various surface functionalized and naked nanomaterials for their drug loading capability and consequently strengthens the Reporting of Observational Studies in Epidemiology (STROBE). We analyzed naked and coated nanoparticles of transition metal oxides for their further loading with doxorubicin, a representative water-soluble anticancer drug.Various uncoated and polyethylene glycol-coated metal oxide nanoparticles were synthesized and loaded with anticancer drug using simple stirring of the nanoparticles in a saturated aqueous solution of the drug. Results showed that surface-coated nanoparticles have higher drug-loading capabilities; however, certain naked metal oxide nanoparticles, such as cobalt oxide nanoparticles, can load a sufficient amount of drug.
    Matched MeSH terms: Doxorubicin/administration & dosage*
  5. Conventional versus Doxorubicin-Eluting Beads Transarterial Chemoembolization for Unresectable Hepatocellular Carcinoma: a Tertiary Medical Centre Experience in Malaysia
    Rahman FA, Naidu J, Ngiu CS, Yaakob Y, Mohamed Z, Othman H, et al.
    Asian Pac J Cancer Prev, 2016;17(8):4037-41.
    PMID: 27644658
    BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer that is frequently diagnosed at an advanced stage. Transarterial chemoembolisation (TACE) is an effective palliative treatment for patients who are not eligible for curative treatment. The two main methods for performing TACE are conventional (c-TACE) or with drug eluting beads (DEB-TACE). We sought to compare survival rates and tumour response between patients undergoing c-TACE and DEB-TACE at our centre.

    MATERIALS AND METHODS: A retrospective cohort study of patients undergoing either treatment was carried out from January 2009 to December 2014. Tumour response to the procedures was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). Kaplan-Meier analysis was used to assess and compare the overall survival in the two groups.

    RESULTS: A total of 79 patients were analysed (34 had c-TACE, 45 had DEB-TACE) with a median follow-up of 11.8 months. A total of 20 patients in the c-TACE group (80%) and 12 patients in the DEB-TACE group (44%) died during the follow up period. The median survival durations in the c-TACE and DEB-TACE groups were 4.9 ± 3.2 months and 8.3 ± 2.0 months respectively (p=0.008). There was no statistically significant difference noted among the two groups with respect to mRECIST criteria.

    CONCLUSIONS: DEB-TACE demonstrated a significant improvement in overall survival rates for patients with unresectable HCC when compared to c-TACE. It is a safe and promising approach and should potentially be considered as a standard of care in the management of unresectable HCC.

    Matched MeSH terms: Doxorubicin/administration & dosage*
  6. Doxorubicin-loaded magnetic gold nanoshells for a combination therapy of hyperthermia and drug delivery
    Mohammad F, Yusof NA
    J Colloid Interface Sci, 2014 Nov 15;434:89-97.
    PMID: 25170601 DOI: 10.1016/j.jcis.2014.07.025
    In the present work, nanohybrid of an anticancer drug, doxorubicin (Dox) loaded gold-coated superparamagnetic iron oxide nanoparticles (SPIONs@Au) were prepared for a combination therapy of cancer by means of both hyperthermia and drug delivery. The Dox molecules were conjugated to SPIONs@Au nanoparticles with the help of cysteamine (Cyst) as a non-covalent space linker and the Dox loading efficiency was investigated to be as high as 0.32 mg/mg. Thus synthesized particles were characterized by HRTEM, UV-Vis, FT-IR, SQUID magnetic studies and further tested for heat and drug release at low frequency oscillatory magnetic fields. The hyperthermia studies investigated to be strongly influenced by the applied frequency and the solvents used. The Dox delivery studies indicated that the drug release efficacy is strongly improved by maintaining the acidic pH conditions and the oscillatory magnetic fields, i.e. an enhancement in the Dox release was observed from the oscillation of particles due to the applied frequency, and is not effected by heating of the solution. Finally, the in vitro cell viability and proliferation studies were conducted using two different immortalized cell lines containing a cancerous (MCF-7 breast cancer) and non-cancerous H9c2 cardiac cell type.
    Matched MeSH terms: Doxorubicin/administration & dosage*
  7. Fulltext FOXP2-positive diffuse large B-cell lymphomas exhibit a poor response to R-CHOP therapy and distinct biological signatures
    Wong KK, Gascoyne DM, Soilleux EJ, Lyne L, Spearman H, Roncador G, et al.
    Oncotarget, 2016 Aug 16;7(33):52940-52956.
    PMID: 27224915 DOI: 10.18632/oncotarget.9507
    FOXP2 shares partially overlapping normal tissue expression and functionality with FOXP1; an established diffuse large B-cell lymphoma (DLBCL) oncogene and marker of poor prognosis. FOXP2 is expressed in the plasma cell malignancy multiple myeloma but has not been studied in DLBCL, where a poor prognosis activated B-cell (ABC)-like subtype display partially blocked plasma cell differentiation. FOXP2 protein expression was detected in ABC-DLBCL cell lines, and in primary DLBCL samples tumoral FOXP2 protein expression was detected in both germinal center B-cell-like (GCB) and non-GCB DLBCL. In biopsies from DLBCL patients treated with immunochemotherapy (R-CHOP), ≥ 20% nuclear tumoral FOXP2-positivity (n = 24/158) correlated with significantly inferior overall survival (OS: P = 0.0017) and progression-free survival (PFS: P = 0.0096). This remained significant in multivariate analysis against either the international prognostic index score or the non-GCB DLBCL phenotype (P < 0.05 for both OS and PFS). Expression of BLIMP1, a marker of plasmacytic differentiation that is commonly inactivated in ABC-DLBCL, did not correlate with patient outcome or FOXP2 expression in this series. Increased frequency of FOXP2 expression significantly correlated with FOXP1-positivity (P = 0.0187), and FOXP1 co-immunoprecipitated FOXP2 from ABC-DLBCL cells indicating that these proteins can co-localize in a multi-protein complex. FOXP2-positive DLBCL had reduced expression of HIP1R (P = 0.0348), which is directly repressed by FOXP1, and exhibited distinct patterns of gene expression. Specifically in ABC-DLBCL these were associated with lower expression of immune response and T-cell receptor signaling pathways. Further studies are warranted to investigate the potential functional cooperativity between FOXP1 and FOXP2 in repressing immune responses during the pathogenesis of high-risk DLBCL.
    Matched MeSH terms: Doxorubicin/administration & dosage
  8. FZD1 activates protein kinase C delta-mediated drug-resistance in multidrug-resistant MES-SA/Dx5 cancer cells
    Hung TH, Chen CM, Tseng CP, Shen CJ, Wang HL, Choo KB, et al.
    Int J Biochem Cell Biol, 2014 Aug;53:55-65.
    PMID: 24814288 DOI: 10.1016/j.biocel.2014.04.011
    Multidrug-resistant (MDR) cancer is a major clinical problem in chemotherapy of cancer patients. We have noted inappropriate PKCδ hypomethylation and overexpression of genes in the PKCδ/AP-1 pathway in the human uterus sarcoma drug-resistant cell line, MES-SA/Dx5 cells, which also overexpress p-glycoprotein (ABCB1). Recent studies have indicated that FZD1 is overexpressed in both multidrug-resistant cancer cell lines and in clinical tumor samples. These data have led us to hypothesize that the FZD1-mediated PKCδ signal-transduction pathway may play an important role in drug resistance in MES-SA/Dx5 cells. In this work, the PKCδ inhibitor Rottlerin was found to reduce ABCB1 expression and to inhibit the MDR drug pumping ability in the MES-SA/Dx5 cells when compared with the doxorubicin-sensitive parental cell line, MES-SA. PKCδ was up-regulated with concurrent up-regulation of the mRNA levels of the AP-1-related factors, c-JUN and c-FOS. Activation of AP-1 also correlated with up-regulation of the AP-1 downstream genes HGF and EGR1. Furthermore, AP-1 activities were reduced and the AP-1 downstream genes were down-regulated in Rottlerin-treated or PKCδ shRNA-transfected cells. MES-SA/Dx5 cells were resensitized to doxorubicin-induced toxicity by co-treatment with doxorubicin and Rottlerin or PKCδ shRNA. In addition, cell viability and drug pump-out ability were significantly reduced in the FZD1 inhibitor curcumin-treated and FZD1 shRNA-knockdown MES-SA/Dx5 cells, indicating involvement of PKCδ in FZD1-modulated ABCB1 expression pathway. Taken together, our data demonstrate that FZD1 regulates PKCδ, and the PKCδ/AP-1 signalling transduction pathway plays an important role in drug resistance in MES-SA/Dx5 cells.
    Matched MeSH terms: Doxorubicin/administration & dosage
  9. Fine needle aspiration cytology of undifferentiated embryonal sarcoma of the liver: a case report
    Sharifah NA, Muhaizan WM, Rahman J, Zulfikar A, Zahari Z
    Malays J Pathol, 1999 Dec;21(2):105-9.
    PMID: 11068415
    The cytological features of a rare case of undifferentiated (embryonal) sarcoma of the liver are presented. The cytology smears showed singly dispersed polygonal and spindle cells as well as loose clusters of cells held together in myxoid material. Neoplastic cells were generally large with round, oval or lobulated nuclei. The cytoplasm was variable in amount with ill-defined borders. Occasional multinucleated cells were also present. Hyaline globules were present on sections of the cell block. Immunohistochemical studies performed showed positivity for vimentin, cytokeratin and alpha-1-antitrypsin (AAT) in the tumour cells.
    Matched MeSH terms: Doxorubicin/administration & dosage
  10. Hemodynamic effects of HPMA copolymer based doxorubicin conjugate: A randomized controlled and comparative spectral study in conscious rats
    Cheah HY, Šarenac O, Arroyo JJ, Vasić M, Lozić M, Glumac S, et al.
    Nanotoxicology, 2017 03;11(2):210-222.
    PMID: 28098511 DOI: 10.1080/17435390.2017.1285071
    Conjugation of Doxorubicin (DOX) to N-(2-hydroxypropyl) methylacrylamide copolymer (HPMA) has significantly reduced the DOX-associated cardiotoxicity. However, the reports on the impact of HPMA-DOX conjugates on the cardiovascular system such as blood pressure (BP) and heart rate (HR) were in restrained animals using tail cuff and/or other methods that lacked the resolution and sensitivity. Herein, we employed radiotelemetric-spectral-echocardiography approach to further understand the in vivo cardiovascular hemodynamics and variability post administration of free DOX and HPMA-DOX. Rats implanted with radio-telemetry device were administered intravenously with DOX (5 mg/kg), HPMA-DOX (5 mg DOX equivalent/kg) and HPMA copolymer and subjected to continuous cardiovascular monitoring and echocardiography for 140 days. We found that DOX-treated rats had ruffled fur, reduced body weight (BW) and a low survival rate. Although BP and HR were normal, spectral analysis indicated that their BP and HR variabilities were reduced. All rats exhibited typical signs of cardiotoxicity at histopathology. In contrast, HPMA-DOX rats gained weight over time and survived. Although BP, HR and related variabilities were unaffected, the left ventricular end diastolic volume (EDV) of these rats, as well as of the HPMA copolymer-treated rats, was found increased at the end of observation period. Additionally, HPMA copolymer caused microscopic injury of the heart tissue. All of these suggest the necessity of caution when employing HPMA as carrier for prolonged drug delivery. The current study also indicates the potential of radiotelemetric-spectral-echocardiography approach for improved preclinical cardiovascular risk assessment of polymer-drug conjugate and other nano-sized-drug constructs.
    Matched MeSH terms: Doxorubicin/administration & dosage
  11. Fulltext Hippuric acid nanocomposite enhances doxorubicin and oxaliplatin-induced cytotoxicity in MDA-MB231, MCF-7 and Caco2 cell lines
    Hussein Al Ali SH, Al-Qubaisi M, Hussein MZ, Ismail M, Bullo S
    Drug Des Devel Ther, 2013;7:25-31.
    PMID: 23345969 DOI: 10.2147/DDDT.S37070
    The aim of the current study is to design a new nanocomposite for inducing cytotoxicity of doxorubicin and oxaliplatin toward MDA-MB231, MCF-7, and Caco2 cell lines. A hippuric acid (HA) zinc layered hydroxide (ZLH) nanocomposite was synthesized under an aqueous environment using HA and zinc oxide (ZnO) as the precursors.
    Matched MeSH terms: Doxorubicin/administration & dosage
  12. Infantile fibrosarcoma of the penis in a 2-year-old boy
    Taib F, Mohamad N, Mohamed Daud MA, Hassan A, Singh MS, Nasir A
    Urology, 2012 Oct;80(4):931-3.
    PMID: 22854139 DOI: 10.1016/j.urology.2012.05.021
    Fibrosarcoma is rare in the pediatric age group. It generally involves the extremities and the trunk but rarely involves the genital area. We report a case of a large fungating infantile fibrosarcoma of the penis in a 2-year-old Malay boy. Partial recovery of the penile structure was achieved after chemotherapy. The difficulty in managing the social and surgical aspect of this case is discussed in our report. To the best of our knowledge, this is the first case report of infantile fibrosarcoma involving the penis in an Asian region.
    Matched MeSH terms: Doxorubicin/administration & dosage
  13. Fulltext Magnetic Properties of Polyvinyl Alcohol and Doxorubicine Loaded Iron Oxide Nanoparticles for Anticancer Drug Delivery Applications
    Nadeem M, Ahmad M, Akhtar MS, Shaari A, Riaz S, Naseem S, et al.
    PLoS One, 2016;11(6):e0158084.
    PMID: 27348436 DOI: 10.1371/journal.pone.0158084
    The current study emphasizes the synthesis of iron oxide nanoparticles (IONPs) and impact of hydrophilic polymer polyvinyl alcohol (PVA) coating concentration as well as anticancer drug doxorubicin (DOX) loading on saturation magnetization for target drug delivery applications. Iron oxide nanoparticles particles were synthesized by a reformed version of the co-precipitation method. The coating of polyvinyl alcohol along with doxorubicin loading was carried out by the physical immobilization method. X-ray diffraction confirmed the magnetite (Fe3O4) structure of particles that remained unchanged before and after polyvinyl alcohol coating and drug loading. Microstructure and morphological analysis was carried out by transmission electron microscopy revealing the formation of nanoparticles with an average size of 10 nm with slight variation after coating and drug loading. Transmission electron microscopy, energy dispersive, and Fourier transform infrared spectra further confirmed the conjugation of polymer and doxorubicin with iron oxide nanoparticles. The room temperature superparamagnetic behavior of polymer-coated and drug-loaded magnetite nanoparticles were studied by vibrating sample magnetometer. The variation in saturation magnetization after coating evaluated that a sufficient amount of polyvinyl alcohol would be 3 wt. % regarding the externally controlled movement of IONPs in blood under the influence of applied magnetic field for in-vivo target drug delivery.
    Matched MeSH terms: Doxorubicin/administration & dosage*
  14. Fulltext Modified methods of nanoparticles synthesis in pH-sensitive nano-carriers production for doxorubicin delivery on MCF-7 breast cancer cell line
    Hamidu A, Mokrish A, Mansor R, Razak ISA, Danmaigoro A, Jaji AZ, et al.
    Int J Nanomedicine, 2019;14:3615-3627.
    PMID: 31190815 DOI: 10.2147/IJN.S190830
    Purpose: Modified top-down procedure was successfully employed in the synthesis of aragonite nanoparticles (NPs) from cheaply available natural seawater cockle shells. This was with the aim of developing a pH-sensitive nano-carrier for effective delivery of doxorubicin (DOX) on MCF-7 breast cancer cell line. Methods: The shells were cleaned with banana pelts, ground using a mortar and pestle, and stirred vigorously on a rotary pulverizing blending machine in dodecyl dimethyl betane solution. This simple procedure avoids the use of stringent temperatures and unsafe chemicals associated with NP production. The synthesized NPs were loaded with DOX to form DOX-NPs. The free and DOX-loaded NPs were characterized for physicochemical properties using field emission scanning electron microscopy, transmission electron microscopy, zeta potential analysis, Fourier transform infrared spectroscopy, and X-ray diffraction. The release profile, cytotoxicity, and cell uptake were evaluated. Results: NPs had an average diameter of 35.50 nm, 19.3% loading content, 97% encapsulation efficiency, and a surface potential and intensity of 19.1±3.9 mV and 100%, respectively. A slow and sustained pH-specific controlled discharge profile of DOX from DOX-NPs was observed, clearly showing apoptosis/necrosis induced by DOX-NPs through endocytosis. The DOX-NPs had IC50 values 1.829, 0.902, and 1.0377 µg/mL at 24, 48, and 72 hrs, while those of DOX alone were 0.475, 0.2483, and 0.0723 µg/mL, respectively. However, even at higher concentration, no apparent toxicity was observed with the NPs, revealing their compatibility with MCF-7 cells with a viability of 92%. Conclusions: The modified method of NPs synthesis suggests the tremendous potential of the NPs as pH-sensitive nano-carriers in cancer management because of their pH targeting ability toward cancerous cells.
    Matched MeSH terms: Doxorubicin/administration & dosage*
  15. Fulltext Multi-Target Approach to Metastatic Adrenal Cell Carcinoma
    Wahab NA, Zainudin S, AbAziz A, Mustafa N, Sukor N, Kamaruddin NA
    Arch Iran Med, 2016 Sep;19(9):671-3.
    PMID: 27631184 DOI: 0161909/AIM.0012
    Adrenal cell carcinoma is a rare tumor and more than 70% of patients present with advanced stages. Adrenal cell carcinoma is an aggressive tumor with a poor prognosis. Surgical intervention is the gold standard treatment and mitotane is the only drug approved for the treatment of adrenal cell carcinoma. Until recently in 2012, the etoposide, doxorubicin, cisplatin plus mitotane are approved as first-line therapy based on response rate and progression-free survival. This case illustrates a case of advanced adrenal cell carcinoma in a young girl who presented with huge adrenal mass with inferior vena cava thrombosis and pulmonary embolism. Multi-approach of therapy was used to control the tumor size and metastasis. Therefore, it may prolong her survival rate for up to 5 years and 4 months.
    Matched MeSH terms: Doxorubicin/administration & dosage
  16. Myasthenia gravis and a rare complication of chemotherapy
    Ng CV
    Med J Aust, 2005 Feb 07;182(3):120.
    PMID: 15698357
    We describe a patient with myasthenia gravis and thymoma who developed recurrent severe myasthenic crises associated with the use of combination chemotherapy.
    Matched MeSH terms: Doxorubicin/administration & dosage
  17. Outcome of treatment in adult acute lymphoblastic leukaemia in an Asian population: comparison with previous multicentre German study
    Bosco I, Teh A
    Leukemia, 1995 Jun;9(6):951-4.
    PMID: 7596183
    Reports on the outcome of treatment in ALL in Asian (non-Caucasian) adults have been few, and published results compare very unfavourably with results of treatment from 'Western' centres. Seventy-four newly diagnosed Malaysian patients with ALL between the ages of 15 and 69 were treated from 1986 to 1990. The clinical features and prognostic factors were similar to those reported in 'Western' series. The chemotherapy protocol utilized was adapted from the one used by Hoelzer et al in the multicentre German study. The complete remission rate was 73%. The probability of continuous complete remission at 5 years was 29% with a median duration of remission of 15 months. This compares with Hoelzer's initial results of 77% CR rate and 35% CCR at 5 years. Patients with an initial white cell count of less than 30 x 10(9)/l at presentation were found to have a significantly better disease-free survival than those with a count of more than 30 x 10(9)/l (35 vs 22%, P = 0.026, univariate analysis). There was no difference in leukaemia-free survival according to age, sex, ethnic group, or immunophenotype. These results show that the use of moderately intensive chemotherapy protocols in Asian (non-Caucasian) patients achieves similar results to those used in Caucasians. We also showed that the difficulties in 'curing' approximately 70% of adult patient with ALL are universal.
    Matched MeSH terms: Doxorubicin/administration & dosage
  18. PXR, CAR and HNF4alpha genotypes and their association with pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin in Asian patients
    Hor SY, Lee SC, Wong CI, Lim YW, Lim RC, Wang LZ, et al.
    Pharmacogenomics J, 2008 Apr;8(2):139-46.
    PMID: 17876342
    Previously studied candidate genes have failed to account for inter-individual variability of docetaxel and doxorubicin disposition and effects. We genotyped the transcriptional regulators of CYP3A and ABCB1 in 101 breast cancer patients from 3 Asian ethnic groups, that is, Chinese, Malays and Indians, in correlation with the pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin. While there was no ethnic difference in docetaxel and doxorubicin pharmacokinetics, ethnic difference in docetaxel- (ANOVA, P=0.001) and doxorubicin-induced (ANOVA, P=0.003) leukocyte suppression was observed, with Chinese and Indians experiencing greater degree of docetaxel-induced myelosuppression than Malays (Bonferroni, P=0.002, P=0.042), and Chinese experiencing greater degree of doxorubicin-induced myelosuppression than Malays and Indians (post hoc Bonferroni, P=0.024 and 0.025). Genotyping revealed both PXR and CAR to be well conserved; only a PXR 5'-untranslated region polymorphism (-24381A>C) and a silent CAR variant (Pro180Pro) were found at allele frequencies of 26 and 53%, respectively. Two non-synonymous variants were identified in HNF4alpha (Met49Val and Thr130Ile) at allele frequencies of 55 and 1%, respectively, with the Met49Val variant associated with slower neutrophil recovery in docetaxel-treated patients (ANOVA, P=0.046). Interactions were observed between HNF4alpha Met49Val and CAR Pro180Pro, with patients who were wild type for both variants experiencing least docetaxel-induced neutropenia (ANOVA, P=0.030). No other significant genotypic associations with pharmacokinetics or pharmacodynamics of either drug were found. The PXR-24381A>C variants were significantly more common in Indians compared to Chinese or Malays (32/18/21%, P=0.035) Inter-individual and inter-ethnic variations of docetaxel and doxorubicin pharmacokinetics or pharmacodynamics exist, but genotypic variability of the transcriptional regulators PAR, CAR and HNF4alpha cannot account for this variability.
    Matched MeSH terms: Doxorubicin/administration & dosage
  19. Fulltext Phase III HEAT Study Adding Lyso-Thermosensitive Liposomal Doxorubicin to Radiofrequency Ablation in Patients with Unresectable Hepatocellular Carcinoma Lesions
    Tak WY, Lin SM, Wang Y, Zheng J, Vecchione A, Park SY, et al.
    Clin Cancer Res, 2018 01 01;24(1):73-83.
    PMID: 29018051 DOI: 10.1158/1078-0432.CCR-16-2433
    Purpose: Lyso-thermosensitive liposomal doxorubicin (LTLD) consists of doxorubicin contained within a heat-sensitive liposome. When heated to ≥40°C, LTLD locally releases a high concentration of doxorubicin. We aimed to determine whether adding LTLD improves the efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC) lesions with a maximum diameter (dmax) of 3 to 7 cm.Experimental Design: The HEAT Study was a randomized, double-blind, dummy-controlled trial of RFA ± LTLD. The 701 enrolled patients had to have ≤4 unresectable HCC lesions, at least one of which had a dmax of 3 to 7 cm. The primary endpoint was progression-free survival (PFS) and a key secondary endpoint was overall survival (OS). Post hoc subset analyses investigated whether RFA duration was associated with efficacy.Results: The primary endpoint was not met; in intention-to-treat analysis, the PFS HR of RFA + LTLD versus RFA alone was 0.96 [95% confidence interval (CI), 0.79-1.18; P = 0.71], and the OS HR ratio was 0.95 (95% CI, 0.76-1.20; P = 0.67). Among 285 patients with a solitary HCC lesion who received ≥45 minutes RFA dwell time, the OS HR was 0.63 (95% CI, 0.41-0.96; P < 0.05) in favor of combination therapy. RFA + LTLD had reversible myelosuppression similar to free doxorubicin.Conclusions: Adding LTLD to RFA was safe but did not increase PFS or OS in the overall study population. However, consistent with LTLD's heat-based mechanism of action, subgroup analysis suggested that RFA + LTLD efficacy is improved when RFA dwell time for a solitary lesion ≥45 minutes. Clin Cancer Res; 24(1); 73-83. ©2017 AACR.
    Matched MeSH terms: Doxorubicin/administration & dosage
  20. Fulltext Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumour of breast
    Ikhwan SM, Kenneth VK, Seoparjoo A, Zin AA
    BMJ Case Rep, 2013 Jun 21;2013.
    PMID: 23813511 DOI: 10.1136/bcr-2013-009584
    Primary primitive neuroectodermal tumour (PNET) and extraskeletal Ewing's sarcoma belongs to the Ewing's family of tumours. Primary tumours arising from breast are very rare. There are only a few case reports published on primary extraskeletal Ewing's sarcoma and PNET arising from breast. We present an extremely rare case of an inoperable primary Ewing's sarcoma arising from left breast with contralateral breast, lymphatic and lung metastasis.
    Matched MeSH terms: Doxorubicin/administration & dosage
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