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  1. 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
  2. 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
  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. 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
  5. 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
  6. Relapsed lymphoma mimicking venous ulcer: A case report
    Kamal WSA, Affandi AM, Bhullar A, Kamal WSZ
    Med J Malaysia, 2018 08;73(4):253-254.
    PMID: 30121690 MyJurnal
    Lymphoma presenting with ulceration is not typical. We report a case of relapsed DLBCL in a 73-year-old man presenting with a chronic non-healing leg ulcer. He has underlying varicose veins with recurrent venous ulcers. This patient was diagnosed to have DLBCL six years earlier when he presented with recurrent epistaxis originating from a left nasal cavity nodule. Complete resolution was achieved after eight cycles of R-CHOP and intrathecal methotrexate. For this current problem, this patient was treated with rituximab combined with chemotherapy which resulted in healing of the ulcer.
    Matched MeSH terms: Doxorubicin/administration & dosage
  7. 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
  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. 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. 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*
  11. 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
  12. 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
  13. 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*
  14. 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
  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. 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*
  17. 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*
  18. Fulltext Primary non-Hodgkin's lymphoma presenting as a uterine cervical mass
    Ab Hamid S, Wastie ML
    Singapore Med J, 2008 Mar;49(3):e73-5.
    PMID: 18362991
    We report a 43-year-old woman who presented with post-coital bleeding. Pelvic examination revealed a uterine cervical mass, which confirmed to be large B cell lymphoma on histopathological examination. Computed tomography showed a primary lesion in the uterine cervix with no lymph node or other extranodal involvement. The patient responded to CHOP (cyclophosphamide, adriamycin, vincristine and prednisolone) chemotherapy regime with no major side effects.
    Matched MeSH terms: Doxorubicin/administration & dosage
  19. 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
  20. 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*
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