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Displaying publications 21 - 29 of 29 in total

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Oral 5-fluorouracil colon-specific delivery through in vivo pellet coating for colon cancer and aberrant crypt foci treatment

Bose A, Elyagoby A, Wong TW

Int J Pharm, 2014 Jul 1;468(1-2):178-86.
PMID: 24709212 DOI: 10.1016/j.ijpharm.2014.04.006

In situ coating of 5-fluorouracil pellets by ethylcellulose and pectin powder mixture (8:3 weight ratio) in capsule at simulated gastrointestinal media provides colon-specific drug release in vitro. This study probes into pharmacodynamic and pharmacokinetic profiles of intra-capsular pellets coated in vivo in rats with reference to their site-specific drug release outcomes. The pellets were prepared by extrusion-spheronization technique. In vitro drug content, drug release, in vivo pharmacokinetics, local colonic drug content, tumor, aberrant crypt foci, systemic hematology and clinical chemistry profiles of coated and uncoated pellets were examined against unprocessed drug. In vivo pellet coating led to reduced drug bioavailability and enhanced drug accumulation at colon (179.13 μg 5-FU/g rat colon content vs 4.66 μg/g of conventional in vitro film-coated pellets at 15 mg/kg dose). The in vivo coated pellets reduced tumor number and size, through reforming tubular epithelium with basement membrane and restricting expression of cancer from adenoma to adenocarcinoma. Unlike uncoated pellets and unprocessed drug, the coated pellets eliminated aberrant crypt foci which represented a putative preneoplastic lesion in colon cancer. They did not inflict additional systemic toxicity. In vivo pellet coating to orally target 5-fluorouracil delivery at cancerous colon is a feasible therapeutic treatment approach.

Matched MeSH terms: Antimetabolites, Antineoplastic/administration & dosage*; Antimetabolites, Antineoplastic/blood; Antimetabolites, Antineoplastic/pharmacokinetics; Antimetabolites, Antineoplastic/chemistry
Fulltext Cost-effectiveness of aspirin adjuvant therapy in early stage colorectal cancer in older patients

Soon SS, Chia WK, Chan ML, Ho GF, Jian X, Deng YH, et al.

PLoS One, 2014;9(9):e107866.
PMID: 25250815 DOI: 10.1371/journal.pone.0107866

Recent observational studies showed that post-operative aspirin use reduces cancer relapse and death in the earliest stages of colorectal cancer. We sought to evaluate the cost-effectiveness of aspirin as an adjuvant therapy in Stage I and II colorectal cancer patients aged 65 years and older.

Matched MeSH terms: Antimetabolites, Antineoplastic/economics; Antimetabolites, Antineoplastic/therapeutic use
Systemic anti-CTLA-4 and intravesical Bacille-Calmette-Guerin therapy in non-muscle invasive bladder cancer: Is there a rationale of synergism?

Fahmy O, Khairul-Asri MG, Stenzl A, Gakis G

Med Hypotheses, 2016 Jul;92:57-8.
PMID: 27241256 DOI: 10.1016/j.mehy.2016.04.037

Although intravesical instillation of Bacille-Calmette-Guerin (BCG) immunotherapy was approved many decades ago as a first line therapy for intermediate to high-risk non-muscle invasive bladder cancer, its long-term efficacy is still arguable as a proportion of up to 30-40% of patients will develop recurrence or progression of their disease. Based on currently available data on the clinical application of checkpoint inhibitors in solid tumors, the mucosa-associated lymphoid tissue seems to be a main target for anti-CTLA-4 antibodies. In this manuscript we hypothesize that the combination of anti-CTLA-4 therapy with BCG might enhance the immune activity in the bladder submucosal tissue, and subsequently, improve oncological outcomes of NMIBC.

Matched MeSH terms: Antimetabolites, Antineoplastic/administration & dosage
Antioxidant value and antiproliferative efficacy of mitragynine and a silane reduced analogue

Goh TB, Koh RY, Mordi MN, Mansor SM

Asian Pac J Cancer Prev, 2014;15(14):5659-65.
PMID: 25081682

BACKGROUND: To investigate the antioxidant value and anticancer functions of mitragynine (MTG) and its silane-reduced analogues (SRM) in vitro.
MATERIALS AND METHODS: MTG and SRM was analyzed for their reducing power ability, ABTS radical inhibition and 1,1-diphenyl-2-picryl hydrazylfree radicals scavenging activities. Furthermore, the antiproliferation efficacy was evaluated using MTT assay on K 562 and HCT116 cancer cell lines versus NIH/3T3 and CCD18-Co normal cell lines respectively.
RESULTS: SRM and MTG demonstrate moderate antioxidant value with ABTS assay (Trolox equivalent antioxidant capacity (TEAC): 2.25±0.02 mmol trolox / mmol and 1.96±0.04 mmol trolox / mmol respectively) and DPPH (IC50=3.75±0.04 mg/mL and IC50=2.28±0.02 mg/mL respectively). Both MTG and SRM demonstrate equal potency (IC50=25.20±1.53 and IC50= 22.19±1.06 respectively) towards K 562 cell lines, comparable to control, betulinic acid (BA) (IC5024.40±1.26). Both compounds showed concentration-dependent cytototoxicity effects and exert profound antiproliferative efficacy at concentration > 100 μM towards HCT 116 and K 562 cancer cell lines, comparable to those of BA and 5-FU (5-Fluorouracil). Furthermore, both MTG and SRM exhibit high selectivity towards HCT 116 cell lines with selective indexes of 3.14 and 2.93 respectively compared to 5-FU (SI=0.60).
CONCLUSIONS: These findings revealed that the medicinal and nutitional values of mitragynine obtained from ketum leaves that growth in tropical forest of Southeast Asia and its analogues does not limited to analgesic properties but could be promising antioxidant and anticancer or chemopreventive compounds.

Matched MeSH terms: Antimetabolites, Antineoplastic/pharmacology
Adjuvant treatment in colorectal cancer. Experience from a referral center in eastern peninsular Malaysia

Biswal BM, Sain AH, Othman NH, Baba A

Trop Gastroenterol, 2002 Jul-Sep;23(3):134-7.
PMID: 12693156

Colorectal cancer is one of the most common malignancies in the West, but in Asia the incidence is low. However in Malaysia, colorectal cancer is increasing with a reported figure of 15% of all cancer cases. Adjuvant chemo and radiotherapy are now more frequently used in such patients. The present retrospective analysis was performed to document the effect of such therapy among patients with colorectal cancer in Malaysia.

Matched MeSH terms: Antimetabolites, Antineoplastic/administration & dosage
Development and evaluation of nanostructured lipid carrier-based hydrogel for topical delivery of 5-fluorouracil

Rajinikanth PS, Chellian J

Int J Nanomedicine, 2016 Oct 5;11:5067-5077.
PMID: 27785014

The aim of this study was to develop a nanostructured lipid carrier (NLC)-based hydrogel and study its potential for the topical delivery of 5-fluorouracil (5-FU). Precirol(®) ATO 5 (glyceryl palmitostearate) and Labrasol(®) were selected as the solid and liquid lipid phases, respectively. Poloxamer 188 and Solutol(®) HS15 (polyoxyl-15-hydroxystearate) were selected as surfactants. The developed lipid formulations were dispersed in 1% Carbopol(®) 934 (poly[acrylic acid]) gel medium in order to maintain the topical application consistency. The average size, zeta potential, and polydispersity index for the 5-FU-NLC were found to be 208.32±8.21 nm, -21.82±0.40 mV, and 0.352±0.060, respectively. Transmission electron microscopy study revealed that 5-FU-NLC was <200 nm in size, with a spherical shape. In vitro drug permeation studies showed a release pattern with initial burst followed by sustained release, and the rate of 5-FU permeation was significantly improved for 5-FU-NLC gel (10.27±1.82 μg/cm(2)/h) as compared with plain 5-FU gel (2.85±1.12 μg/cm(2)/h). Further, skin retention studies showed a significant retention of 5-FU from the NLC gel (91.256±4.56 μg/cm(2)) as compared with that from the 5-FU plain gel (12.23±3.86 μg/cm(2)) in the rat skin. Skin irritation was also significantly reduced with 5-FU-NLC gel as compared with 5-FU plain gel. These results show that the prepared 5-FU-loaded NLC has high potential to improve the penetration of 5-FU through the stratum corneum, with enormous retention and with minimal skin irritation, which is the prerequisite for topically applied formulations.

Matched MeSH terms: Antimetabolites, Antineoplastic/administration & dosage
LOC285629 regulates cell proliferation and motility in colorectal cancer cells

Nasir SN, Abu N, Ab Mutalib NS, Ishak M, Sagap I, Mazlan L, et al.

Clin Transl Oncol, 2018 Jun;20(6):775-784.
PMID: 29098557 DOI: 10.1007/s12094-017-1788-x

PURPOSE: Colorectal cancer (CRC) is one of the most widely diagnosed cancers in men and women worldwide. With the advancement of next-generation sequencing technologies, many studies have highlighted the involvement of long non-coding RNAs (lncRNAs) in cancer development. Growing evidence demonstrates that lncRNAs play crucial roles in regulating gene and protein expression and are involved in various cancers, including CRC. The field of lncRNAs is still relatively new and a lot of novel lncRNAs have been discovered, but their functional roles are yet to be elucidated. This study aims to characterize the expression and functional roles of a novel lncRNA in CRC.
METHOD: Several methods were employed to assess the function of LOC285629 such as gene silencing, qPCR, proliferation assay, BrdU assay, transwell migration assay, ELISA and protein profiler.
RESULTS: Via in silico analyses, we identified significant downregulation of LOC285629, a novel lncRNA, across CRC stages. LOC285629 expression was significantly downregulated in advanced stages (Stage III and IV) compared to Stage I (Kruskal-Wallis Test; p = 0.0093). Further in-house validation showed that the expression of LOC285629 was upregulated in colorectal cancer tissues and cell lines compared to the normal counterparts, but was downregulated in advanced stages. By targeting LOC285629, the viability, proliferative abilities, invasiveness and resistance of colorectal cancer cells towards 5-fluorouracil were reduced. It was also discovered that LOC285629 may regulate cancer progression by targeting several different proteins, namely survivin, BCL-xL, progranulin, PDGF-AA, enolase 2 and p70S6 K.
CONCLUSION: Our findings suggest that LOC285629 may be further developed as a potential therapeutic target for CRC treatment.

Matched MeSH terms: Antimetabolites, Antineoplastic/pharmacology
Splenic infarct as a diagnostic pitfall in radiology

Joshi SC, Pant I, Shukla AN, Anshari MA

J Cancer Res Ther, 2008 8 9;4(2):99-101.
PMID: 18688130

Follow-up of colorectal carcinoma after therapy is based on symptoms, tumor markers, and imaging studies. Clinicians sometimes face diagnostic dilemmas because of unusual presentations on the imaging modalities coupled with rising serum markers. We report a case of colorectal carcinoma that presented with gastrointestinal symptoms 14 months after completion of treatment. Investigations showed rise in carcinoembryonic antigen (CEA). Suspecting disease recurrence, complete radioimaging workup was performed; the only abnormality detected was a smooth, hypodense area in the posterior third of the spleen on contrast-enhanced computed tomography abdomen. In view of the previous diagnosis of carcinoma colon, the symptoms reported by the patient, the elevated CEA, and the atypical CECT appearance, a diagnosis of splenic metastasis was made. The patient was subjected to splenectomy as a curative treatment. However, the histopathological report revealed it to be a splenic infarct. The present case reemphasizes the limitations of radiological studies in the follow-up of carcinoma colon.

Matched MeSH terms: Antimetabolites, Antineoplastic/therapeutic use
Identification of inhibitors synergizing gemcitabine sensitivity in the squamous subtype of pancreatic ductal adenocarcinoma (PDAC)

Er JL, Goh PN, Lee CY, Tan YJ, Hii LW, Mai CW, et al.

Apoptosis, 2018 Jun;23(5-6):343-355.
PMID: 29740790 DOI: 10.1007/s10495-018-1459-6

Pancreatic adenocarcinoma (PDAC) is a highly aggressive cancer with a high chance of recurrence, limited treatment options, and poor prognosis. A recent study has classified pancreatic cancers into four molecular subtypes: (1) squamous, (2) immunogenic, (3) pancreatic progenitor and (4) aberrantly differentiated endocrine exocrine. Among all the subtypes, the squamous subtype has the worst prognosis. This study aims to utilize large scale genomic datasets and computational systems biology to identify potential drugs targeting the squamous subtype of PDAC through combination therapy. Using the transcriptomic data available from the International Cancer Genome Consortium, Cancer Cell Line Encyclopedia and Connectivity Map, we identified 26 small molecules that could target the squamous subtype of PDAC. Among them include inhibitors targeting the SRC proto-oncogene (SRC) and the mitogen-activated protein kinase kinase 1/2 (MEK1/2). Further analyses demonstrated that the SRC inhibitors (dasatinib and PP2) and MEK1/2 inhibitor (pimasertib) synergized gemcitabine sensitivity specifically in the squamous subtype of PDAC cells (SW1990 and BxPC3), but not in the PDAC progenitor cells (AsPC1). Further analysis revealed that the synergistic effects are dependent on SRC or MEK1/2 activities, as overexpression of SRC or MEK1/2 completely abrogated the synergistic effects SRC inhibitors (dasatinib and PP2) and MEK1/2 inhibitor (pimasertib). In contrast, no significant toxicity was observed in the MRC5 human lung fibroblast and ARPE-19 human retinal pigment epithelial cells. Together, our findings suggest that combinations of SRC or MEK inhibitors with gemcitabine possess synergistic effects on the squamous subtype of PDAC cells and warrant further investigation.

Matched MeSH terms: Antimetabolites, Antineoplastic/therapeutic use*