Displaying publications 1 - 20 of 29 in total

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  1. Targeted polymeric nanoparticle for anthracycline delivery in hypoxia-induced drug resistance in metastatic breast cancer cells
    Almoustafa HA, Alshawsh MA, Chik Z
    Anticancer Drugs, 2021 Aug 01;32(7):745-754.
    PMID: 33675612 DOI: 10.1097/CAD.0000000000001065
    Poly lactic-co-glycolic acid (PLGA) nanoparticles are intensively studied nanocarriers in drug delivery because of their biodegradability and biochemical characteristics. Polyethylene glycol (PEG) coating for nanocarriers gives them long circulation time in blood and makes them invisible to the reticuloendothelial system. Breast cancer cells have greater uptake of hyaluronic acid compared to normal cells as it binds to their overexpressed CD44 receptors. Since hypoxia plays an important role in cancer metastasis; we formulated PEG-PLGA nanoparticles coated with hyaluronic acid as targeted delivery system for doxorubicin (DOX) using nanoprecipitation method, and characterized them for chemical composition, size, surface charge, shape, and encapsulation efficiency. Then we tested them in vitro on hypoxia-optimized metastatic breast cancer cells. The nanoparticles were spherical with an average size of about 106 ± 53 nm, a negative surface charge (-15 ± 3 mV), and high encapsulation efficiency (73.3 ± 4.1%). In vitro investigation with hypoxia-elevated CD44 MDA-MB-231 cells showed that hyaluronic acid-targeted nanoparticles maintained their efficacy despite hypoxia-induced drug resistance unlike free DOX and nontargeted nanoparticles. In conclusion, this study revealed a simple third generation nanoparticle formulation for targeted treatment of hypoxia-induced drug resistance in breast cancer metastatic cells. Further, optimization is needed including In vivo efficacy and nanoparticle-specific pharmacokinetic studies.
    Matched MeSH terms: Doxorubicin/administration & dosage
  2. 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
  3. Treatment options for locally advanced breast cancer--experience in an Asian tertiary hospital
    Chong HY, Taib NA, Rampal S, Saad M, Bustam AZ, Yip CH
    Asian Pac J Cancer Prev, 2010;11(4):913-7.
    PMID: 21133600
    BACKGROUND: Locally advanced breast cancer (LABC) is characterized by the presence of a large primary tumour (>5 cm) associated with or without skin or chest-wall involvement (T4) or with fixed (matted) axillary lymph nodes in the absence of any evidence of distant metastases. These cancers are classified as stage IIIA and IIIB according to the AJCC Staging System. Treatment of choice involves combinations of surgery, chemotherapy, radiotherapy and/or hormonal therapy. Current guidelines recommend primary surgery or neoadjuvant therapy followed by surgery. The primary objective of this study was to compare the outcome of LABC patients subjected to neoadjuvant chemotherapy before surgery and those who underwent surgery as the primary treatment and to determine prognostic predictors. Secondary objectives were to evaluate the response after neoadjuvant therapy and to determine the treatment compliance rate.

    METHODS: This retrospective study of Stage III breast cancer patients was conducted over a 5 year period from 1998 to 2002. The survival data were obtained from the National Registry of Births and Deaths with the end-point of the study in April 2006. The Kaplan Meier method was applied for survival analysis. Cox regression analysis by stepwise selection was performed to identify important prognostic factors.

    RESULTS: Out of a 155 evaluable patients, 74 (47.7%) had primary surgery, 62 (40%) had neoadjuvant chemotherapy, 10 patients (6.5%) were given Tamoxifen as the primary treatment, while 9 patients (5.8%) defaulted any form of treatment. After neoadjuvant chemotherapy, 9 patients defaulted further treatment, leaving 53 evaluable patients. Out of these 53 evaluable patients, 5 patients (9.4%) had complete pathological response, 5 (9.4%) a complete clinical response, and 26 (49.1%) had partial response after neoadjuvant chemotherapy. The 5-year survival in the primary surgery group was 56.7 % compared to 44.7% in the neoadjuvant chemotherapy group (p<0.01). The important prognostic factors were race, size of tumour, nodal status, estrogen receptor status and response to neoadjuvant chemotherapy.

    CONCLUSION: Patients who had primary surgery had better survival than those who underwent neoadjuvant chemotherapy, which may be due to bias in the selection of patients for neoadjuvant chemotherapy. Out of a total of 155 patients, 25.1% defaulted part of the treatment, or did not receive optimal treatment, emphasizing the importance of psychosocial support and counselling for this group of patients.

    Matched MeSH terms: Doxorubicin/administration & dosage
  4. 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*
  5. 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
  6. 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*
  7. Fulltext Synergistic inhibition of melanoma xenografts by Brequinar sodium and Doxorubicin
    Dorasamy MS, Ab A, Nellore K, Wong PF
    Biomed Pharmacother, 2019 Feb;110:29-36.
    PMID: 30458345 DOI: 10.1016/j.biopha.2018.11.010
    Malignant melanoma continues to be a fatal disease for which novel and long-term curative breakthroughs are desired. One such innovative idea would be to assess combination therapeutic treatments - by way of combining two potentially effective and very different therapy. Previously, we have shown that DHODH inhibitors, A771726 and Brequinar sodium (BQR) induced cell growth impairment in melanoma cells. Similar results were seen with DHODH RNA interference (shRNA). In the present study, we showed that combination of BQR with doxorubicin resulted in synergistic and additive cell growth inhibition in these cells. In addition, in vivo studies with this combination of drugs demonstrated an almost 90% tumor regression in nude mice bearing melanoma tumors. Cell cycle regulatory proteins, cyclin B1 and its binding partner pcdc-2 and p21 were significantly downregulated and upregulated respectively following the combined treatment. Given that we have observed synergistic effects with BQR and doxorubicin, both in vitro and in vivo, these drugs potentially represent a new combination in the targeted therapy of melanoma.
    Matched MeSH terms: Doxorubicin/administration & dosage*
  8. 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
  9. 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
  10. 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*
  11. 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*
  12. 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
  13. 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*
  14. Treatment of childhood acute lymphoblastic leukemia in Malaysia, 1976-1982
    Lin HP, Sinnah D, Menaka N, Cherian R, Singh P
    Med. Pediatr. Oncol., 1983;11(5):327-32.
    PMID: 6579342
    One hundred four children with acute lymphoblastic leukaemia were diagnosed at the University Hospital, Kuala Lumpur, Malaysia, between 1976 and 1982; 87 were evaluable with respect to treatment. They were divided into good prognosis (GP) and bad prognosis (BP) groups based on their initial total white cell count, their treatment differing only during the maintenance phase. Remission was achieved in 82 patients (94%) of whom ten (12%) subsequently died in remission from infection. Twenty-eight (34%) relapsed while on treatment and three while off therapy. Eleven patients ceased treatment after 3 yr of continuous complete remission (CCR). Three of these later relapsed, two within the first year. Survival in CCR was significantly better in the GP group up to 30 months, after which the difference diminished. There was no difference in survival between boys and girls. The overall disease-free survival at 3 yr and 5 yr was 40% and 25%, respectively, with a median follow-up period of 20 months (range 4-69 months). The reasons for the relatively low survival rates as compared with those in developed countries are discussed.
    Matched MeSH terms: Doxorubicin/administration & dosage
  15. 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*
  16. 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
  17. 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
  18. 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*
  19. Fulltext Thermally-responsive Virus-like Particle for Targeted Delivery of Cancer Drug
    Thong QX, Biabanikhankahdani R, Ho KL, Alitheen NB, Tan WS
    Sci Rep, 2019 03 08;9(1):3945.
    PMID: 30850643 DOI: 10.1038/s41598-019-40388-x
    Multifunctional nanocarriers displaying specific ligands and simultaneously response to stimuli offer great potentials for targeted and controlled drug delivery. Several synthetic thermally-responsive nanocarriers have been studied extensively for hyperthermia incorporated chemotherapy. However, no information is available on the application of virus-like particle (VLP) in thermally-controlled drug delivery systems. Here, we describe the development of a novel multifunctional nanovehicle based on the VLP of Macrobrachium rosenbergii nodavirus (MrNVLP). Folic acid (FA) was covalently conjugated to lysine residues located on the surface of MrNVLP, while doxorubicin (Dox) was loaded inside the VLP using an infusion method. This thermally-responsive nanovehicle, namely FA-MrNVLP-Dox, released Dox in a sustained manner and the rate of drug release increased in response to a hyperthermia temperature at 43 °C. The FA-MrNVLP-Dox enhanced the delivery of Dox to HT29 cancer cells expressing high level of folate receptor (FR) as compared to CCD841CoN normal cells and HepG2 cancer cells, which express low levels of FR. As a result, FA-MrNVLP-Dox increased the cytotoxicity of Dox on HT29 cells, and decreased the drug's cytotoxicity on CCD841CoN and HepG2 cells. This study demonstrated the potential of FA-MrNVLP-Dox as a thermally-responsive nanovehicle for targeted delivery of Dox to cancer cells rich in FR.
    Matched MeSH terms: Doxorubicin/administration & dosage*
  20. Fulltext pH-responsive Virus-like Nanoparticles with Enhanced Tumour-targeting Ligands for Cancer Drug Delivery
    Biabanikhankahdani R, Alitheen NBM, Ho KL, Tan WS
    Sci Rep, 2016 11 24;6:37891.
    PMID: 27883070 DOI: 10.1038/srep37891
    Multifunctional nanocarriers harbouring specific targeting moieties and with pH-responsive properties offer great potential for targeted cancer therapy. Several synthetic drug carriers have been studied extensively as drug delivery systems but not much information is available on the application of virus-like nanoparticles (VLNPs) as multifunctional nanocarriers. Here, we describe the development of pH-responsive VLNPs, based on truncated hepatitis B virus core antigen (tHBcAg), displaying folic acid (FA) for controlled drug delivery. FA was conjugated to a pentadecapeptide containing nanoglue bound on tHBcAg nanoparticles to increase the specificity and efficacy of the drug delivery system. The tHBcAg nanoparticles loaded with doxorubicin (DOX) and polyacrylic acid (PAA) demonstrated a sustained drug release profile in vitro under tumour tissue conditions in a controlled manner and improved the uptake of DOX in colorectal cancer cells, leading to enhanced antitumour effects. This study demonstrated that DOX-PAA can be packaged into VLNPs without any modification of the DOX molecules, preserving the pharmacological activity of the loaded DOX. The nanoglue can easily be used to display a tumour-targeting molecule on the exterior surface of VLNPs and can bypass the laborious and time-consuming genetic engineering approaches.
    Matched MeSH terms: Doxorubicin/administration & dosage*
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