Three patients presenting with distinct clinical variants of porokeratosis are reported. This article discusses the etiology, classification and response to different modalities of treatment.
Triple negative breast cancer (TNBC) is the most aggressive intrinsic breast cancer subtype characterized by the lack of estrogen receptor (ER), progesterone receptor (PR), and low levels of human epidermal growth factor receptor 2 (HER2). The complex nature of TNBC has resulted in little therapeutic progress for the past several decades. The standard of care remains the FEC cocktail (5-fluorouracil (5-FU), epirubicin and cyclophosphamide). However, early relapse and metastasis in TNBC patients persists in causing dismal clinical outcomes. Due to complex heterogeneity features of TNBC, identifying the biomarker associated to the chemoresistance remains a challenge. The emergence of the long non-coding RNA (lncRNA) as a potential signature may have proven to be a new deterrent to diagnostic and treatment options. Previous studies unveiled the associations of lncRNA in the development of TNBCs whereby the aggressiveness and response to therapies may be associated by the abrogation of the molecular mechanism lncRNA. Terminal differentiation induced ncRNA (TINCR) is a lncRNA which have been linked with many cancers including TNBC. The expression and behavior of TINCR may exert unfavorable outcome in TNBCs. Nevertheless, the underlying molecular mechanism of TINCR in driving chemoresistance in TNBC is not well understood. This review will highlight the potential molecular mechanisms of TINCR in TNBC chemoresistance and how it can serve as a future potential prognostic and therapeutic target for a better treatment intervention.
Blastocystis is an enteric protozoan parasite with extensive genetic variation and unclear pathogenicity. It is commonly associated with gastrointestinal symptoms such as nausea, diarrhea, vomiting and abdominal pain in immunocompromised individuals. In this study, we explored the in vitro and in vivo effects of Blastocystis on the activity of a commonly used CRC chemotherapeutic agent, 5-FU. The cellular and molecular effects of solubilized antigen of Blastocystis in the presence of 5-FU were investigated using HCT116, human CRC cell line and CCD 18-Co, normal human colon fibroblast cells. For the in vivo study, 30 male Wistar rats were divided into six groups, as follows; Control Group: oral administration of 0.3 ml Jones' medium, Group A: rats injected with azoxymethane (AOM), Group A-30FU: Rats injected with AOM and administered 30 mg/kg 5-FU, Group B-A-30FU: rats inoculated with Blastocystis cysts, injected with AOM and administered 30 mg/kg 5-FU, Group A-60FU: rats injected with AOM and administered 60 mg/kg 5-FU and Group B-A-60FU: rats inoculated with Blastocystis cysts, injected with AOM and administered 60 mg/kg 5-FU. The in vitro study revealed that the inhibitory potency of 5-FU at 8 μM and 10 μM was reduced from 57.7% to 31.6% (p
Matched MeSH terms: Fluorouracil/pharmacology; Fluorouracil/therapeutic use
Nowadays, nano-platforms designed for drug delivery systems (DDSs) such as polymers, liposomes, and micelles have been demonstrated to be clinically efficient. The sustained drug release is one of the advantages of DDSs, especially polymer-based nanoparticles. The formulation could enhance the drug's durability, in which the biodegradable polymers are the most interesting building blocks of DDSs. Nano-carriers could circumvent many issues by localized drug delivery and release via certain internalization routes such as intracellular endocytosis paths and increasing biocompatibility. Polymeric nanoparticles and their nanocomposite are one of the most important classes of materials that can be used for the assembly of nanocarriers that can form complex, conjugated and encapsulated forms. The site-specific drug delivery may arise from the ability of nanocarriers to pass through the biological barrier, their specific interactions with receptors, and passive targeting. The better circulation, uptake, and stability along with targeting attributes lead to lesser side effects and damage to normal cells. Hence, in this review, the most recent achievements on polycaprolactone-based or -modified nanoparticles in drug delivery systems (DDSs) for 5-fluorouracil (5-FU) are presented.
Objectives: Isolation of Leptospira by culture represents a definitive growth and confirmation of the disease, yet it is hampered with its nature of slow growth. With slight modification of culture method, the study aims to isolate and characterize Leptospira spp. from patients with acute febrile illness. Methods: A total of 109 blood samples were collected from patients with acute febrile illness that presented at the Emergency Department of Hospital Universiti Sains Malaysia, Malaysia. Clinical samples were subjected to Leptospira IgM Rapid test, microscopic agglutination test (MAT), isolation by culture method, and direct real-time PCR test. For leptospiral isolation, the samples (whole blood and deposit from spun plasma) were cultured into modified Ellinghausen McCullough Johnson Harris (EMJH) media with and without 5'-fluorouracil (5-FU). In every culture positive sample, partial 16S rRNA gene sequencing was performed for molecular identification of the isolates. Phylogenetic analysis was carried out to determine the genetic relatedness among the isolates. An inhibition of 5-FU study was performed on Leptospirainterrogans serovar Canicola with different concentrations to compare the growth detection of the tested Leptospira with or without 5-FU within 7 days of incubation. Results: Leptospirosis was diagnosed in 14.7% of patients with acute febrile illness. Two Leptospira spp. (n = 2/109, 1.85%) were successfully isolated from whole blood and deposit from spun plasma samples. B004 and B208 samples were positive at day 11 and day 7, respectively, in EMJH media without addition of 5-FU. Sample B004 was identified as Leptospira interrogans and B208 as Leptospira weilli. Phylogenetic analysis confirmed that both of them were within pathogenic group and they were not related. The 5-FU inhibition study revealed that additional of 5-FU at final concentration of 200 µg/mL to EMJH media demonstrated an inhibitory effect on the growth of the tested strain Conclusion: Isolation of Leptospira spp. using EMJH media without addition of 5'-fluorouracil resulted in a better outcome. Two pathogenic Leptospira isolates were successfully cultivated from patients with acute febrile illness that were genetically not related.
Conventional fluid-bed and immersion film coating of hydrophilic zinc pectinate pellets by hydrophobic ethylcellulose is met with fast drug release. This study explored in situ intracapsular pellet coating for colon-specific delivery of 5-fluorouracil (5-FU). The solid coating powder constituted ethylcellulose and pectin in weight ratios of 11:0 to 2:9. Its weight ratio to pellets varied between 2:3 and 3:2. Pectin was used as excipient of core pellets and coating powder in view of its potential use in colon cancer treatment. Delayed 5-FU release and core pectin dissolution were attainable when the weight ratio of solid coating powder to pellets was kept at 3:2, and weight ratio of ethylcellulose and pectin in coating powder was kept at 8:3 with particle size of ethylcellulose reduced to 22 μm. In situ intracapsular wetting of pectin coat by dissolution medium resulted in the formation of ethylcellulose plug interconnecting with pellets through the binding action of pectin. Less than 25% of drug was released at the upper gastrointestinal tract. The majority of drug was released upon prolonged dissolution and in response to colonic enzyme pectinase, which digested core pellets.
Perdagangan lintas sempadan antara Sabah-Sarawak dan Kalimantan secara informal telah wujud sejak sebelumnya konfrontasi Indonesia berlaku pada tahun 1962-1966. Dalam hal ini, penyeludupan barangan di kawasan sempadan turut merupakan satu fenomena yang berterusan sehingga sekarang. Oleh itu, artikel ini ditulis bagi membincangkan mengenai fenomena penyeludupan barangan di kawasan sempadan dengan melihat kepada pandangan komuniti berkaitan permasalahan ini. Kajian ini menggunakan temu bual secara mendalam dan pemerhatian ke atas 15 orang informan bagi melihat kepada fenomena penyeludupan di kawasan kajian. Dapatan kajian mendapati bahawa sejarah perdagangan dan kekeluargaan di kedua-dua kawasan mempunyai kaitan dengan berlangsungnya aktiviti penyeludupan barangan dalam kalangan komuniti sempadan. Persepsi daripada komuniti dan pihak penguatkuasa turut mempengaruhi kelangsungan fenomena tersebut disebabkan sejarah perdagangan dan hubungan kekeluargaan yang dimiliki oleh kedua-dua komuniti sempadan. Namun demikian, dari sudut pandang nasional, fenomena tersebut merupakan satu aktiviti yang menyalahi undang-undang yakni penyeludupan. Oleh itu, bertitik-tolak daripada faktor tersebut isu ini terus berlaku di kawasan kajian.
This study focuses on the use of ethosome and microwave technologies to facilitate skin penetration and/or deposition of 5-fluorouracil in vitro and in vivo. Low ethanol ethosomes were designed and processed by mechanical dispersion technique and had their size, zeta potential, morphology, drug content and encapsulation efficiency characterized. The skin was pre-treated with microwave at 2450 MHz for 2.5 min with ethosomes applied topically and subjected to in vitro and in vivo skin drug permeation as well as retention evaluation. The drug and/or ethosomes cytotoxicity, uptake and intracellular trafficking by SKMEL-28 melanoma cell culture were evaluated. Pre-treatment of skin by microwave promoted significant drug deposition in skin from ethosomes in vitro while keeping the level of drug permeation unaffected. Similar observations were obtained in vivo with reduced drug permeation into blood. Combination ethosome and microwave technologies enhanced intracellular localization of ethosomes through fluidization of cell membrane lipidic components as well as facilitating endocytosis by means of clathrin, macropinocytosis and in particularly lipid rafts pathways. The synergistic use of microwave and ethosomes opens a new horizon for skin malignant melanoma treatment.
Leptospires are preserved by frequent sub-culturing in semisolid media due to the challenge of low recovery by freezing or liquid nitrogen methods. The present study evaluated three liquid EMJH medium compositions (Medium A: Leptospira medium base EMJH, Leptospira enrichment EMJH, 5-fluorouracil (3%), rabbit serum (1%) and calf serum (1%); Medium B: same as Medium A but without 5-fluorouracil; Medium C: same as Medium B but with the addition of sodium pyruvate) for the revival of leptospires after storage at -80 °C. A total of 18 Leptospira serovars cultured in Medium A was aliquoted into cryogenic vials and directly stored at -80 °C. A hundred microlitre from each serovar culture stored at -80 °C was sub-cultured on a selected time over a period of 30 months into Media A, B and C. Regrowth on Media B and C showed a better and faster recovery (89-100%) (p-value <0.05) compared to Medium A (67-100%). Leptospires can be stored longer at -80 °C and a good recovery could be obtained when sub-cultured on EMJH medium without 5-fluorouracil.
Dihydropyrimidine dehydrogenase (DPD) is a pyrimidine catabolic enzyme involved in the initial and rate-limiting step of the catabolic pathway of toxic metabolites of 5-fluorouracil (5-FU). Several studies have reported that deficiency of DPD and polymorphisms of its gene are related to 5-FU toxicities and death. Association between serum concentration of 5-FU and its related toxicity has also been previously demonstrated. Hence, this study aims to understand the role of DPYD variants in serum level of 5-FU and the risk of developing toxicity to prevent adverse reactions and maximize therapy outcome for personalized medicine.
Polysaccharide-based magnetic nanocomposites can eminently illuminate several attractive features as anticancer drug carriers. In this study, rice straw-based cellulose nanowhisker (CNW) was used as solid support for Fe3O4 nanofillers to synthesize magnetic CNW. Then, cross-linked chitosan-coated magnetic CNW for 5-fluorouracil carrier abbreviated as CH/MCNW/5FU. Fourier-transform infrared, X-Ray diffraction, and X-ray photoelectron spectroscopy analysis indicated successful fabrication and multifunctional properties of the CH/MCNW/5FU nanocomposites. In addition, CH/MCNW/5FU nanocomposites showed hydrodynamic diameter and zeta potential value of 181.31 ± 3.46 nm and +23 ± 1.8 mV, respectively. Based on images of transmission electron microscopy, magnetic CNW as reinforcement was coated with chitosan to obtain almost spherical CH/MCNW/5FU nanocomposites with an average diameter of 37.16 ± 3.08. The nanocomposites indicated desired saturation magnetization and thermal stability, high drug encapsulation efficiency, and pH-dependent swelling and drug release performance. CH/MCNW/5FU nanocomposites showed potent killing effects against colorectal cancer cells in both 2D monolayer and 3D spheroid models. These findings suggest CH/MCNW as a potential carrier for anticancer drugs with high tumour-penetrating capacity.
Drug delivery constitutes the formulations, technologies, and systems for the transport of pharmaceutical compounds to specific areas in the body to exert safe therapeutic effects. The main criteria for selecting the correct medium for drug delivery are the quantity of the drug being carried and the amount of time required to release the drug. Hence, this research aimed to improve the aforementioned criteria by synthesizing a medium based on calcium carbonate-nanocellulose composite and evaluating its efficiency as a medium for drug delivery. Specifically, the efficiency was assessed in terms of the rates of uptake and release of 5-fluorouracil. Through the evaluation of the morphological and chemical properties of the synthesized composite, the established 3D printing profiles of nanocellulose and CaCO3 took place following the layer-by-layer films. The 3D printed double laminated CaCO3-nanocellulose managed to release the 5-fluorouracil as an effective single composition and in a time-controlled manner.
There has been significant progress in the last few decades in addressing the biomedical applications of polymer hydrogels. Particularly, stimuli responsive hydrogels have been inspected as elegant drug delivery systems capable to deliver at the appropriate site of action within the specific time. The present work describes the synthesis of pH responsive semi-interpenetrating network (semi-IPN) hydrogels of N-succinyl-chitosan (NSC) via Schiff base mechanism using glutaraldehyde as a crosslinking agent and Poly (acrylamide-co-acrylic acid)(Poly (AAm-co-AA)) was embedded within the N-succinyl chitosan network. The physico-chemical interactions were characterized by Fourier transform infrared (FTIR), X-ray diffraction (XRD), thermogravimetric analysis (TGA), and field emission scanning electron microscope (FESEM). The synthesized hydrogels constitute porous structure. The swelling ability was analyzed in physiological mediums of pH 7.4 and pH 1.2 at 37°C. Swelling properties of formulations with various amounts of NSC/ Poly (AAm-co-AA) and crosslinking agent at pH 7.4 and pH 1.2 were investigated. Hydrogels showed higher swelling ratios at pH 7.4 while lower at pH 1.2. Swelling kinetics and diffusion parameters were also determined. Drug loading, encapsulation efficiency, and in vitro release of 5-fluorouracil (5-FU) from the synthesized hydrogels were observed. In vitro release profile revealed the significant influence of pH, amount of NSC, Poly (AAm-co-AA), and crosslinking agent on the release of 5-FU. Accordingly, rapid and large release of drug was observed at pH 7.4 than at pH 1.2. The maximum encapsulation efficiency and release of 5-FU from SP2 were found to be 72.45% and 85.99%, respectively. Kinetics of drug release suggested controlled release mechanism of 5-FU is according to trend of non-Fickian. From the above results, it can be concluded that the synthesized hydrogels have capability to adapt their potential exploitation as targeted oral drug delivery carriers.
This study aims to evaluate the practice of adjuvant chemotherapy in colorectal cancer at the Institute of Radiotherapy and Oncology, Hospital Kuala Lumpur. A retrospective analysis of 320 patients' records from 1986 to 1994 was carried out. Adjuvant chemotherapy was given to 98 patients. Cancers of the rectum and sigmoid colon constituted over 60% of the patients. All the regimes used were 5-fluorouracil-based. The oral route was the most commonly used (55.1%). Toxicity was seldom the reason for stopping treatment (2%). The adjuvant treatment employed has been tolerable while the survival was comparable with other centres.
Controlled release delivery system of chemotherapeutic agents at the site of colon endorses modern drug-entrapped delivery tools, which release the entrappedagents at a controlled rate for anextended period providing patient compliance and additional protection from the degradinggastric environment. Thus, the present study was aimed to develop and optimize a novel polymeric microsphere of 5-fluorouracil (5-FU) using natural gum katira to obtain an optimal therapeutic response at the colon. Due course of experimentation, in-vivo safety profile of the gum katira in an animal model was established. Modified solvent extraction/evaporation technique wasemployed to encapsulate 5-FU in the natural polymeric microsphere and was characterized using in-vitro studies to investigate particle size, morphology, encapsulation efficiency and release of the drug from developed formulation. Formulated and optimized polymeric microsphere of 5-FU using gum katira polymer own optimal physicochemical characteristics with a fine spherical particle with size ranged from 210.37±7.50 to 314.45±7.80 μm.Targeted microsphere exhibited good cytotoxicity and also has high drug entrapment efficiency, and satisfactory release pattern of the drug within a time frame of 12 h. Finally, we foresee that the optimized polymeric gum katiramicrosphere of 5-FU could be a promising micro-carrier for efficient colon drug targeting delivery tool with improved chemotherapeutic efficacy against colon cancer.
5-Fluororaucil (5-FU) as anti-cancer drug was reported to induce thymidine synthase (TS) overexpression and cancer cell resistance. To improve its therapeutic efficacy and selective targeting, here we developed a targeted delivery system mediated by the active ligand-folate receptor chemistry to deliver the 5-FU drug selectively into the tumor microenvironment. The preparation was achieved by exploring chitosan (CS)-biopolymer based system with folic acid (FA)-conjugation. The 5-FU@FACS-Mn:ZnS quantum dots (QDs) based on the histological assessment conducted in the 4T1 challenged mice showed an improved tumor remission in the liver, spleen and lungs. The 5-FU@FACS-Mn:ZnS composite induced anti-proliferative properties in these organs as compared to the free 5-FU drug. Unlike the 5-FU@FACS-Mn:ZnS treated groups which showed some specific morphological changes such as cell shrinkage without obvious presence of adipocytes, the excised section of the tumor in the untreated control group and the free 5-FU drug treated group showed necrotic and degenerated cells; these cells are multifocally distributed in the tumor mass with evidence of widely distributed adipocytes within the tumor mass. These findings suggest that the 5-FU@FACS-Mn:ZnS composite has a superior role during the induction of apoptosis in the 4T1 cells as compared to the free 5-FU drug treated groups. The results of the study therefore suggest that the impregnation of 5-FU anti-cancer drug within the FACS-Mn:ZnS system significantly improves its selective targeting efficacy, in addition to improving the anti-proliferative properties and attenuate possible tumor resistances to the 5-FU drug. The work discusses about the anti-metastatic effects of folic acid-bound 5-Fluororacil loaded Mn:ZnS quantum dots towards 4T1 cell line proliferation in mice based on the histological analysis.
Ensuring adherence to chemotherapy is important to prevent disease progression, prolong survival and sustain good quality of life. Capecitabine is a complex chemotherapeutic agent with many side effects that might affect patient adherence to treatment. This cross sectional study aimed to determine adherence to capecitabine and its contributing factors among cancer outpatients in Malaysia. One hundred and thirteen patients on single regime capecitabine were recruited from Hospital Sultan Ismail and Hospital Kuala Lumpur from October 2013 to March 2014. Adherence was determined based on adherence score using validated Medication Compliance Questionnaire. Patient socio-demographics, disease, and treatment characteristics were obtained from medical records. Satisfaction score was measured using the validated Patient Satisfaction with Healthcare questionnaire. The mean adherence score was 96.1% (standard deviation: 3.29%). The significant contributing factors of adherence to capecitabine were Malay ethnicity [β=1.3; 95% confidence interval (CI): 0.21, 2.43; p value=0.020], being female [β=1.8; 95%CI: 0.61, 2.99; p value=0.003]), satisfaction score [β=0.08; 95%CI: 0.06, 1.46; p value=0.035], presence of nausea or vomiting [β=2.3; 95%CI: 1.12, 3.48; p value <0.001] and other side effects [β=1.45; 95%CI: 0.24, 2.65; p value=0.019]. Adherence to capecitabine was generally high in our local population. Attention should be given to non-Malay males and patients having nausea, vomiting or other side effects. Sufficient information, proactive assessment and appropriate management of side effects would improve patient satisfaction and thus create motivation to adhere to treatment plans.
Matched MeSH terms: Fluorouracil/adverse effects; Fluorouracil/analogs & derivatives*; Fluorouracil/therapeutic use
A hospital based cross-sectional retrospective study was conducted to determine the frequency of hand foot syndrome (HFS) with Capecitabine as a single agent and in combination with Oxaliplatin. The study included 43 consecutive cases of colorectal carcinoma and conducted from June till December 2008. Patients on palliative care were excluded. SPSS was used for the application of chi-square test, by keeping the level of significance as p < 0.05. Fifteen (34.9%) patients developed HFS, 10 in the single-agent and 5 in the combination group. No significant association of HFS with either regimens was noted (p=0.876).