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Photodynamic application of protoporphyrin IX as a photosensitizer encapsulated by silica nanoparticles

Makhadmeh GN, Abdul Aziz A

Artif Cells Nanomed Biotechnol, 2018;46(sup3):S1043-S1046.
PMID: 30449196 DOI: 10.1080/21691401.2018.1528982

BACKGROUND: Achieved Silica Nanoparticles (SiNPs) to encapsulate the photosensitizer [Protoporphyrin IX (PpIX)] in photodynamic therapy (PDT) application was reported in this research.
MATERIALS AND METHODS: Cytotoxicity for five different concentrations of encapsulated and naked PpIX was measured. Optimum concentration and optimum exposure time of encapsulated and naked PpIX that needed to destroy the cells (Osteosarcoma cells) was measured.
RESULTS: The results showed that the encapsulated PpIX has more efficacy compared to the naked PpIX and the applicability of the encapsulated PpIX-SiNPs was proved on osteosarcoma cells.
CONCLUSION: The results established the important in-vitro photodynamic effectiveness of PpIX-SiNP, which may open a new application for PpIX in its clinical and in-vitro studies.

Matched MeSH terms: Osteosarcoma/drug therapy*
Fulltext Osteosarcoma: the outcome of limb salvage surgery

Faisham WI, Zulmi W, Halim AS, Biswal BM, Mutum SS

Med J Malaysia, 2004 Dec;59 Suppl F:24-34.
PMID: 15941157

We reviewed the surgical and oncological management 23 consecutive patients with osteosarcoma of the long bones to determine the outcome of limb salvage technique performed in our centre. All patients received neoadjuvant chemotherapy. There were 15 males and 8 females with a mean age at diagnosis of 19 years (9 to 36). The median follow-up was 30 months (10 to 60). Fifteen had lesion around the knee joint followed by three in the proximal humerus, two in distal humerus, two in the pelvis, and one in the distal tibia. Six patients presented with lung metastases at diagnosis. We performed limb salvage surgery to control local disease in 16 patients and amputation in 7. The resection margins of the primary lesion were adequate and free of tumour cells in all patients. Local recurrence developed in 1 patient of limb salvage group. The overall median survival was 22 months and actuarial survival was 52% at 3 years. Eleven patients died of pulmonary metastases within 2 years of follow-up. Median survival of the limb salvage surgery group was 30 months compared to 6 months in the amputation group. As per our experience, limb salvage technique is a feasible option in extremity osteosarcoma without compromising survival.

Matched MeSH terms: Osteosarcoma/drug therapy
p53 Status does not affect photodynamic cell killing induced by hypericin

Lee HB, Ho AS, Teo SH

Cancer Chemother Pharmacol, 2006 Jul;58(1):91-8.
PMID: 16211395

Given that p53 is a tumor suppressor that plays a central role in the cellular response to DNA damage and that more than 50% of all cancers have mutated p53, the wider utility of photodynamic therapy (PDT) in the treatment of cancer will depend on an understanding of whether p53 status modulates response to PDT. In this study, we investigated the photosensitivity of isogenic cell lines that differ only in their p53 status to PDT using hypericin as the photosensitizer.

Matched MeSH terms: Osteosarcoma/drug therapy
Fulltext Major surgery in an osteosarcoma patient refusing blood transfusion: case report

Dhanoa A, Singh VA, Shanmugam R, Rajendram R

World J Surg Oncol, 2010;8:96.
PMID: 21059231 DOI: 10.1186/1477-7819-8-96

We describe an unusual case of osteosarcoma in a Jehovah's Witness patient who underwent chemotherapy and major surgery without the need for blood transfusion. This 16-year-old girl presented with osteosarcoma of the right proximal tibia requiring proximal tibia resection, followed by endoprosthesis replacement. She was successfully treated with neoadjuvant chemotherapy and surgery with the support of haematinics, granulocyte colony-stimulating factor, recombinant erythropoietin and intraoperative normovolaemic haemodilution. This case illustrates the importance of maintaining effective, open communication and exploring acceptable therapeutic alternative in the management of these patients, whilst still respecting their beliefs.

Matched MeSH terms: Osteosarcoma/drug therapy
An unusual mutation in RECQ4 gene leading to Rothmund-Thomson syndrome

Balraj P, Concannon P, Jamal R, Beghini A, Hoe TS, Khoo AS, et al.

Mutat Res, 2002 Oct 31;508(1-2):99-105.
PMID: 12379465

Rothmund-Thomson syndrome (OMIM #268400) is a severe autosomal recessive genodermatosis: characterised by growth retardation, hyperpigmentation and frequently accompanied by congenital bone defects, brittle hair and hypogonadism. Mutations in helicase RECQ4 gene are responsible for a subset of cases of RTS. Only six mutations have been reported, thus, far and each affecting the coding sequence or the splice junctions. We report the first homozygous mutation in RECQ4 helicase: 2746-2756-delTGGGCTGAGGC in IVS8 responsible for the severe phenotype associated with RTS in a Malaysian pedigree. We report also a 5321 G-->A transition in exon 17 and the updated list of the RECQ4 gene mutations.

Matched MeSH terms: Osteosarcoma/drug therapy
Fulltext Emerging Anticancer Potentials of Selenium on Osteosarcoma

Pang KL, Chin KY

Int J Mol Sci, 2019 Oct 25;20(21).
PMID: 31731474 DOI: 10.3390/ijms20215318

Selenium is a trace element essential to humans and forms complexes with proteins, which exert physiological functions in the body. In vitro studies suggested that selenium possesses anticancer effects and may be effective against osteosarcoma. This review aims to summarise current evidence on the anticancer activity of inorganic and organic selenium on osteosarcoma. Cellular studies revealed that inorganic and organic selenium shows cytotoxicity, anti-proliferative and pro-apoptotic effects on various osteosarcoma cell lines. These actions may be mediated by oxidative stress induced by selenium compounds, leading to the activation of p53, proapoptotic proteins and caspases. Inorganic selenium is selective towards cancer cells, but can cause non-selective cell death at a high dose. This condition challenges the controlled release of selenium from biomaterials. Selenium treatment in animals inoculated with osteosarcoma reduced the tumour size, but did not eliminate the incidence of osteosarcoma. Only one study investigated the relationship between selenium and osteosarcoma in humans, but the results were inconclusive. In summary, although selenium may exert anticancer properties on osteosarcoma in experimental model systems, its effects in humans require further investigation.

Matched MeSH terms: Osteosarcoma/drug therapy*
Fulltext Curcumin Analog DK1 Induces Apoptosis in Human Osteosarcoma Cells In Vitro through Mitochondria-Dependent Signaling Pathway

Aziz MNM, Hussin Y, Che Rahim NF, Nordin N, Mohamad NE, Yeap SK, et al.

Molecules, 2018 Jan 05;23(1).
PMID: 29303982 DOI: 10.3390/molecules23010075

Osteosarcoma is one of the primary malignant bone tumors that confer low survival rates for patients even with intensive regime treatments. Therefore, discovery of novel anti-osteosarcoma drugs derived from natural products that are not harmful to the normal cells remains crucial. Curcumin is one of the natural substances that have been extensively studied due to its anti-cancer properties and is pharmacologically safe considering its ubiquitous consumption for centuries. However, curcumin suffers from a poor circulating bioavailability, which has led to the development of a chemically synthesized curcuminoid analog, namely (Z)-3-hydroxy-1-(2-hydroxyphenyl)-3-phenylprop-2-en-1-one (DK1). In this study, the cytotoxic effects of the curcumin analog DK1 was investigated in both U-2OS and MG-63 osteosarcoma cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and cell death was microscopically examined via acridine orange/propidium iodide (AO/PI) double staining. Flow cytometer analysis including Annexin V/Fluorescein isothiocyanate (FITC), cell cycle analysis and JC-1 were adapted to determine the mode of cell death. Subsequently in order to determine the mechanism of cell death, quantitative polymerase chain reaction (qPCR) and proteome profiling was carried out to measure the expression of several apoptotic-related genes and proteins. Results indicated that DK1 induced U-2 OS and MG-63 morphological changes and substantially reduced cell numbers through induction of apoptosis. Several apoptotic genes and proteins were steadily expressed after treatment with DK1; including caspase 3, caspase 9, and BAX, which indicated that apoptosis occurred through a mitochondria-dependent signaling pathway. In conclusion, DK1 could be considered as a potential candidate for an anti-osteosarcoma drug in the near future, contingent upon its ability to induce apoptosis in osteosarcoma cell lines.

Matched MeSH terms: Osteosarcoma/drug therapy
Fulltext In vitro delivery and controlled release of Doxorubicin for targeting osteosarcoma bone cancer

Kamba SA, Ismail M, Hussein-Al-Ali SH, Ibrahim TA, Zakaria ZA

Molecules, 2013 Aug 30;18(9):10580-98.
PMID: 23999729 DOI: 10.3390/molecules180910580

Drug delivery systems are designed to achieve drug therapeutic index and enhance the efficacy of controlled drug release targeting with specificity and selectivity by successful delivery of therapeutic agents at the desired sites without affecting the non-diseased neighbouring cells or tissues. In this research, we developed and demonstrated a bio-based calcium carbonate nanocrystals carrier that can be loaded with anticancer drug and selectively deliver it to cancer cells with high specificity by achieving the effective osteosarcoma cancer cell death without inducing specific toxicity. The results showed pH sensitivity of the controlled release characteristics of the drug at normal physiological pH 7.4 with approximately 80% released within 1,200 min but when exposed pH 4.8 the corresponding 80% was released in 50 min. This study showed that the DOX-loaded CaCO₃ nanocrystals have promising applications in delivery of anticancer drugs.

Matched MeSH terms: Osteosarcoma/drug therapy*