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.
As the cellular prion protein (PrP(C)) has been implicated in carcinogenesis, we aimed to investigate the effects of cancer cell-specific PrP(C) overexpression from the invasion, metastasis, and apoptosis aspects, by performing cell motility assays, cell proliferation assays under anchorage-dependent and anchorage-independent conditions, and apoptosis evasion when subjected to multiple anti-cancer drugs. Overexpression of PrP(C) in LS 174T was achieved by stable transfection. PrP(C) overexpression was shown to increase cell proliferation in anchorage-dependent and anchorage-independent manners, as shown by more viable cells in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, more colonies formed in soft agar assay and increased resistance to anoikis in poly-2-hydroxyethyl methacrylate-coated surface. PrP(C) overexpression also increased cell motility and invasiveness of LS 174T. Cell adhesion to extracellular matrix using collagen- and fibronectin-coated surfaces revealed increased cell attachment in LS 174T cells overexpressing PrP(C). Analysis of apoptotic and necrotic cells by propidium iodide/annexin V-fluorescein isothiocyanate microscopy and 7-amino-actinomycin D/annexin V-phycoerythrin flow cytometry revealed that PrP(C) overexpression attenuated doxorubicin-induced apoptosis. Human apoptosis antibody array with 35 apoptosis-related proteins revealed that three inhibitor of apoptosis proteins (IAPs)-survivin, X-linked inhibitor of apoptosis protein (XIAP), and cellular inhibitor of apoptosis protein-1 (cIAP-1)-were upregulated in LS 174T cells overexpressing PrP(C) in doxorubicin-induced apoptosis. In conclusion, the overexpression of PrP(C) could enhance the invasiveness and survival of LS 174T colorectal cancer cells, indicating that PrP(C) plays a role in colorectal cancer biology.
γ-synuclein, a neuronal protein of the synuclein family, is involved in carcinogenesis. To investigate its role in colorectal cancer carcinogenesis, we overexpressed γ-synuclein in LS 174T colon adenocarcinoma cell line (termed LS 174T-γsyn). When compared with untransfected/mock transfectants, LS 174T-γsyn had higher mobility in scratch wound assay, tend to scatter more in cell-scattering assay, and had enhanced lamellipodia and filopodia formation in cell-spreading assay. Enhanced adhesion of LS 174T-γsyn to fibronectin and collagen and significantly higher proliferation rate showed that γ-synuclein was able to increase extracellular matrix interaction and promoted proliferation of LS 174T. Higher invasiveness of LS 174T-γsyn was evidenced by enhanced invasion to the bottom of the basement membrane in Boyden chamber assay. However, LS 174T-γsyn were significantly more vulnerable to doxorubicin, vincristine and hydrogen peroxide insults, via apoptotic cell death. LS 174T-γsyn also had reduced anchorage-independent growth as shown by reduced colony formation and reduced anoikis resistance. We found that overexpression of γ-synuclein confers both pro-invasive and doxorubicin-mediated pro-apoptotic properties to LS 174T, where the former was mediated through enhanced cyclic adenosine monophosphate response element binding protein (CREB) phosphorylation, while the latter involved hepatocyte growth factor (HGF) downregulation and subsequent downstream signalling pathways possibly involving extracellular signal-regulated kinases (ERK)1/2, p38α, c-Jun N-terminal kinase (JNK) pan and Signal Transducers and Activators of Transcription (STATs). This unexpected contrasting finding as compared to other similar studies on colon cancer cell lines might be correlated with the degree of tumour advancement from which the cell lines were derived from.
Doxorubicin (DOX) adalah salah satu ubat kemoterapi yang paling berkesan untuk merawat pelbagai neoplasma seperti leukemia, limfoma dan kanser payudara. Walau bagaimanapun, ia sering dikaitkan dengan kardiomiopati. Pada masa ini, tiada rawatan yang sesuai untuk mengurangkan kesan kardiomiopati tanpa kesan sampingan yang ketara. Oleh itu, kajian ini bertujuan untuk mengkaji kesan-kesan perlindungan potensi ekstrak benih padi (RSE) terhadap kesitotoksikan yang disebabkan oleh DOX menggunakan kajian kultur sel vitro. Keupayaan antioksidan RSE dinilai, dan hasilnya menunjukkan jumlah kandungan fenolik yang lebih rendah (TPC), tetapi jumlah kandungan flavonoid total (TFC) dan kapasiti antioksidan yang setara trolox (TEAC), dibandingkan dengan ekstrak benih wheatgrass. Satu siri eksperimen spektroskopi penyerapan dan pendarfluor menunjukkan bahawa RSE boleh menghalang pembentukan kompleks DOX-DNA pada kepekatan yang diuji. Tambahan pula, daya maju sel kardiomiosit sel, H9c2 (2-1), telah diuji selepas 24, 48 dan 72 jam rawatan DOX terhadap RSE menggunakan ujian proliferasi sel berdasarkan garam tetrazolium (MTS reagent). Hasilnya menunjukkan kesan perlindungan yang signifikan terhadap RSE terhadap kesitotoksikan yang disebabkan oleh DOX. Jalur sel karsinoma nasofarinks, HK1, digunakan sebagai kawalan untuk menentukan sama ada keberkesanan DOX terjejas oleh pentadbiran bersama RSE. Hasilnya tidak menunjukkan kesan negatif terhadap keberkesanan dadah. Pelbagai sifat berfaedah RSE menunjukkan potensi kuatnya untuk membangunkan agen kardioprotektif untuk melengkapi rawatan DOX dalam tetapan klinikal.
This paper describes a new validated high performance liquid chromatography (HPLC) method for the simultaneous determination of two anti-cancer drugs, Arabinoside-C (Ara-C) and doxorubicin hydrochloride (DOX). A simultaneous determination method saves cost and time as both drugs can be injected into a single HPLC system without the need to change or re-equilibrate with a new mobile phase. The objective of the study is to develop a simultaneous determination method of two anti-cancer drugs, Ara-C and DOX. The mobile phase consisted of a mixture (45:55) of acetonitrile:ammonium hydrogen phosphate aqueous solution (0.01 M) at pH 6.2 at a flow rate of 0.3 ml/min, with UV detection at 252 nm. Separation was achieved on a C-18 column (5 µm: 250 mm × 4.6 mm) maintained at 30°C in a column oven. The method was linear between 325 ng/ml and 10 µg/ml for Ara-C and 625 ng/ml and 20 µg/ml for DOX. The limit of detection (LOD) was 20 ng/ml for Ara-C and 60 ng/ml for DOX. The developed HPLC method achieved good precision and accuracy as well as limit of quantitations. The developed and validated method is suitable to be used for routine analysis of Ara-C and DOX.
INTRODUCTION: The use of e-cigarettes (EC) has reached alarming proportions among Malaysians. On a national level, little is known about the profile and perceptions of Malaysian EC users. This study aimed to explore the prevalence of long-term EC usage and its associated factors among EC users in Malaysia.
METHODS: This nationwide online questionnaire survey was administered among 694 EC users across 13 states and 1 Federal Territory in Malaysia, between January and April 2018. A survey link was e-mailed to EC users that were recruited from an official national vape entity through their Facebook association page. We obtained information on respondents' sociodemographic characteristics, smoking habits, long-term e-cigarette usage and perceptions of EC use. We estimated long-term EC user prevalence and fitted multivariate regression models to predict factors associated with long-term EC usage. Statistical significance was set at p<0.05.
RESULTS: Respondents were predominantly Malays (87.6%), aged >30 years (68.1%) and tertiary educated (71%). The majority were employed (93.1%) with a monthly household income of MYR 4000 or less (56.6%). About 84% were former smokers, while 10% were current smokers. The prevalence of long-term EC usage in this study was 82.3%. Most users believed that EC had helped them to cut down tobacco smoking (94.8%), reduced the urge to smoke (88.3%) and ultimately helped them to quit smoking (87.2%). Respondents aged >30 years and those who perceived that EC has helped them stop smoking were significantly more likely to be long-term EC users.
CONCLUSIONS: Most respondents engaged in EC use to quit smoking. They were more likely to be long-term EC users if they were older and perceived that EC has helped them to quit smoking. This information is valuable for targeted prevention, health promotion and policy regulations.
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.
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.
Fluorouracil, doxorubicin, cyclophosphamide protocol (FAC) is a commonly used regimen for breast cancer due to its proven efficacy, acceptable toxicity, high affordability. While hepatic insufficiency dosing for doxorubicin and fluorouracil have been set, there is paucity of data in the literature on how to reduce doses in renal insufficiency. We sought to determine whether there is an association with pre-chemotherapy creatinine clearance, and the occurrence of clinically significant grade 3 to 5 neutropenia during the course of FAC chemotherapy.
The leaves of Nerium indicum Mill. have been utilized traditionally to cure cancer. By Bioassay (BST) guided isolation method, six compounds were isolated from the CHCl3 extract of the leaves. Selectivity of these compounds (in 0.6-12,500 ng/ml) was tested on various human cancer (MCF7, EVSA-T, T47D, H226, IGROV, A498, WIDR, M19, HeLa) and normal (Vero) cells in vitro. Doxorubicin and cysplatin were used as positive controls. The result indicated that NiO2D (5alpha-oleandrin) possessed the best cytotoxic effect on HeLa cells (IC50, 8.38 x10(-6) mM) and NiO2C (16, 17-dehidrodeasetil-5alpha-oleandrin) on A498 cells (IC50, 1.43 x 10(-6) mM). Those two compounds were not cytotoxic to normal cell.
Matched MeSH terms: Doxorubicin/pharmacology; Doxorubicin/therapeutic use
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.
One hundred and fifty patients with urothelial tumours were reviewed. They form the majority of patients with bladder cancer referred to the Institute of Urology over the past three years. From the study it becomes very apparent that the majority of patients are seen late in the course of their disease. The results of treatment of patients with early lesions have been satisfactory but the patients with late invasive lesions have very poor prognosis. A plea is made that one be more aware of this condition and that symptoms of haematuria and urinary tract infections should have a full urological assessment early.
Nasopharyngeal carcinoma (NPC) is one of the commonest presentation of head and neck cancers in Malaysia, especially in the Chinese. The standard treatment is radical radiotherapy to the post-nasal space and the neck. Chemotherapy is given to patients with primary advanced disease and to patients with recurrence. The study reviews results of chemotherapy given to 33 patients at the University Hospital, Kuala Lumpur, over the last four years.
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; Doxorubicin/therapeutic use
We describe a patient with myasthenia gravis and thymoma who developed recurrent severe myasthenic crises associated with the use of combination chemotherapy.
NK/T cell lymphoma, nasal type is an aggressive and uncommon malignancy. Disease that occurs outside of the aerodigestive tract exhibits an even more aggressive clinical behaviour and does not respond as well to conventional therapy compared to its nasal counterpart. We report such a case of NK/T cell lymphoma, nasal type, that presented as an anterior chest wall mass, arising from the left pectoralis muscle. An interesting feature we wish to highlight is the associated eosinophilia that corresponded to disease activity, exhibiting fluctuations with surgical resection and chemotherapy. To the best of our knowledge this is the third reported case of NK/T cell lymphoma that is associated with peripheral eosinophilia. Our case highlights the role of certain NK cell subsets that play a major role in eosinophilic activation in NK/T lymphomas and calls for more research into further classification of this disease by virtue of its NK cell subsets.
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.
Targeted drug delivery is one of the key challenges in cancer nanomedicine. Stoichiometric and spatial control over the antibodies placement on the nanomedicine vehicle holds a pivotal role to overcome this key challenge. Here, a DNA tetrahedral is designed with available conjugation sites on its vertices, allowing to bind one, two, or three cetuximab antibodies per DNA nanostructure. This stoichiometrically definable cetuximab conjugated DNA nanostructure shows enhanced targeting on the breast cancer cells, which results with higher overall killing efficacy of the cancer cells.
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.