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Fulltext Monitoring T Cells Responses Mounted by Therapeutic Cancer Vaccines

Lim KP, Zainal NS

Front Mol Biosci, 2021;8:623475.
PMID: 33937323 DOI: 10.3389/fmolb.2021.623475

With the regulatory approval of Provenge and Talimogene laherparepvec (T-VEC) for the treatment of metastatic prostate cancer and advanced melanoma respectively, and other promising clinical trials outcomes, cancer vaccine is gaining prominence as a cancer therapeutic agent. Cancer vaccine works to induce T cell priming, expansion, and infiltration resulting in antigen-specific cytotoxicity. Such an approach that can drive cytotoxicity within the tumor could complement the success of checkpoint inhibitors as tumors shown to have high immune cell infiltration are those that would respond well to these antibodies. With the advancements in cancer vaccine, methods to monitor and understand how cancer vaccines modify the immune milieu is under rapid development. This includes using ELISpot and intracellular staining to detect cytokine secretion by activated T cells; tetramer and CyTOF to quantitate the level of antigen specific T cells; proliferation and cell killing assay to detect the expansion of T cell and specific killing activity. More recently, T cell profiling has provided unprecedented detail on immune cell subsets and providing clues to the mechanism involved in immune activation. Here, we reviewed cancer vaccines currently in clinical trials and highlight available techniques in monitoring the clinical response in patients.

Matched MeSH terms: Melanoma
Folate-induced nanostructural changes of oligochitosan nanoparticles and their fate of cellular internalization by melanoma

Musalli AH, Talukdar PD, Roy P, Kumar P, Wong TW

Carbohydr Polym, 2020 Sep 15;244:116488.
PMID: 32536388 DOI: 10.1016/j.carbpol.2020.116488

This study examined the effects of folate environment of oligochitosan nanoparticles on their cellular internalization profiles in human melanoma cells. The conjugates and nanoparticles of oligochitosan-folate, oligochitosan-carboxymethyl-5-fluorouracil, and oligochitosan-folate-carboxymethyl-5-fluorouracil were synthesized by carbodiimide chemistry and prepared by nanospray drying technique respectively. The cellular internalization profiles of oligochitosan-folate nanoparticles against the human malignant melanoma cell line (SKMEL-28) were evaluated using confocal scanning electron microscopy technique through fluorescence labelling and endocytic inhibition, as a function of nanoparticulate folate content, size, polydispersity index, zeta potential, shape, surface roughness and folate population density. The cytotoxicity and cell cycle arrest characteristics of oligochitosan-folate-carboxymethyl-5-fluorouracil nanoparticles, prepared with an optimal folate content that promoted cellular internalization, were evaluated against the oligochitosan-folate and oligochitosan-carboxymethyl-5-fluorouracil conjugate nanoparticles. The oligochitosan-folate conjugate nanoparticles were endocytosed by melanoma cells via caveolae- and lipid raft-mediated endocytic pathways following them binding to the cell surface folate receptor. Nanoparticles that were larger and with higher folic acid contents and zeta potentials exhibited a higher degree of cellular internalization. Excessive conjugation of nanoparticles with folate resulted in a high nanoparticulate density of folate which hindered nanoparticles-cell interaction via folate receptor binding and reduced cellular internalization of nanoparticles. Conjugating oligochitosan with 20 %w/w folate was favorable for cellular uptake as supported by in silico models. Conjugating of oligochitosan nanoparticles with carboxymethyl-5-fluorouracil and 20 %w/w of folate promoted nanoparticles-folate receptor binding, cellular internalization and cancer cell death via cell cycle arrest at S phase at a lower drug dose than oligochitosan-carboxymethyl-5-fluorouracil conjugate nanoparticles and neat carboxymethyl-5-fluorouracil.

Matched MeSH terms: Melanoma/drug therapy*
Chitosan-Carboxymethyl-5-Fluorouracil-Folate Conjugate Particles: Microwave Modulated Uptake by Skin and Melanoma Cells

Nawaz A, Wong TW

J Invest Dermatol, 2018 11;138(11):2412-2422.
PMID: 29857069 DOI: 10.1016/j.jid.2018.04.037

5-Fluorouracil delivery profiles in the form of chitosan-folate submicron particles through skin and melanoma cells in vitro were examined using microwaves as the penetration enhancer. The in vivo pharmacokinetic profile of 5-fluorouracil was also determined. Chitosan-carboxymethyl-5-fluorouracil-folate conjugate was synthesized and processed into submicron particles by spray-drying technique. The size, zeta potential, morphology, drug content, and drug release, as well as skin permeation and retention, pharmacokinetics, in vitro SKMEL-28 melanoma cell line cytotoxicity, and intracellular trafficking profiles of drug/particles, were examined as a function of skin/melanoma cell treatment by microwaves at 2,450 MHz for 5 + 5 minutes. The level of skin drug/particle retention in vitro and in vivo increased in skin treated by microwaves. This was facilitated by the drug conjugating to chitosan and microwaves fluidizing both the protein and lipid domains of epidermis and dermis. The uptake of chitosan-folate particles by melanoma cells was mediated via lipid raft route. It was promoted by microwaves, which fluidized the lipid and protein regimes of the cell membrane, and this increased drug cytotoxicity. In vivo pharmacokinetic study indicated skin treatment by microwave-enhanced drug retention but not permeation. The combination of microwaves and submicron particles synergized skin drug retention and intracellular drug delivery.

Matched MeSH terms: Melanoma/drug therapy*
5-Fluorouracil ethosomes - skin deposition and melanoma permeation synergism with microwave

Khan NR, Wong TW

Artif Cells Nanomed Biotechnol, 2018;46(sup1):568-577.
PMID: 29378453 DOI: 10.1080/21691401.2018.1431650

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.

Matched MeSH terms: Melanoma/pathology*
Panduratin A induces protective autophagy in melanoma via the AMPK and mTOR pathway

Lai SL, Mustafa MR, Wong PF

Phytomedicine, 2018 Mar 15;42:144-151.
PMID: 29655680 DOI: 10.1016/j.phymed.2018.03.027

BACKGROUND: Targeting autophagy is emerging as a promising strategy in cancer therapeutics in recent years. Autophagy can be modulated to drive cancer cell deaths that are notoriously resistant to apoptotic-inducing drugs. In addition, autophagy has been implicated as a prosurvival mechanism in mediating cancer chemoresistance. Our previous study has demonstrated that Panduratin A (PA), a plant-derived active compound exploits ER-stress-mediated apoptosis as its cytotoxic mechanism on melanoma.
PURPOSE: Our previous proteomics analysis revealed that treatment with PA resulted in the upregulation of an autophagy marker, LC3B in melanoma cells. Therefore, the present study sought to investigate the role of PA-induced autophagy in melanoma cells.
METHODS: Transmission electron microscopy was performed for examination of autophagic ultra-structures in PA-treated A375 cells. Cytoplasmic LC3B and p62/SQSMT1 punctate structures were detected using immunofluorescene staining. Expression levels of LC3B II, p62/SQSMT1, ATG 12, Beclin 1, phospho S6 (ser235/236), phospho AMPK (Thr172) and cleaved PARP were evaluated by western blotting.
RESULTS: Autophagosomes, autolysosomes and punctuates of LC3 proteins could be observed in PA-treated A375 cells. PA-induced autophagy in A375 melanoma cells was found to be mediated through the inhibition of mTOR signaling and activation of AMPK pathway. Furthermore, we showed that PA-induced apoptosis was increased in the presence of an autophagy inhibitor, signifying the cytoprotective effect of PA-induced autophagy in melanoma cells.
CONCLUSION: Taken together, results from the present study suggest that the inhibition of autophagy by targeting mTOR and AMPK could potentiate the cytotoxicity effects of PA on melanoma cells.

Matched MeSH terms: Melanoma/drug therapy*; Melanoma/metabolism; Melanoma/pathology
Fulltext Synergistic inhibition of melanoma xenografts by Brequinar sodium and Doxorubicin

Dorasamy MS, Ab A, Nellore K, Wong PF

Biomed Pharmacother, 2019 Feb;110:29-36.
PMID: 30458345 DOI: 10.1016/j.biopha.2018.11.010

Malignant melanoma continues to be a fatal disease for which novel and long-term curative breakthroughs are desired. One such innovative idea would be to assess combination therapeutic treatments - by way of combining two potentially effective and very different therapy. Previously, we have shown that DHODH inhibitors, A771726 and Brequinar sodium (BQR) induced cell growth impairment in melanoma cells. Similar results were seen with DHODH RNA interference (shRNA). In the present study, we showed that combination of BQR with doxorubicin resulted in synergistic and additive cell growth inhibition in these cells. In addition, in vivo studies with this combination of drugs demonstrated an almost 90% tumor regression in nude mice bearing melanoma tumors. Cell cycle regulatory proteins, cyclin B1 and its binding partner pcdc-2 and p21 were significantly downregulated and upregulated respectively following the combined treatment. Given that we have observed synergistic effects with BQR and doxorubicin, both in vitro and in vivo, these drugs potentially represent a new combination in the targeted therapy of melanoma.

Matched MeSH terms: Melanoma/drug therapy*; Melanoma/pathology
Fulltext The Role of PPARβ/δ in Melanoma Metastasis

Lim JCW, Kwan YP, Tan MS, Teo MHY, Chiba S, Wahli W, et al.

Int J Mol Sci, 2018 Sep 20;19(10).
PMID: 30241392 DOI: 10.3390/ijms19102860

BACKGROUND: Peroxisome proliferator⁻activated receptor (PPAR) β/δ, a ligand-activated transcription factor, is involved in diverse biological processes including cell proliferation, cell differentiation, inflammation and energy homeostasis. Besides its well-established roles in metabolic disorders, PPARβ/δ has been linked to carcinogenesis and was reported to inhibit melanoma cell proliferation, anchorage-dependent clonogenicity and ectopic xenograft tumorigenicity. However, PPARβ/δ's role in tumour progression and metastasis remains controversial.
METHODS: In the present studies, the consequence of PPARβ/δ inhibition either by global genetic deletion or by a specific PPARβ/δ antagonist, 10h, on malignant transformation of melanoma cells and melanoma metastasis was examined using both in vitro and in vivo models.
RESULTS: Our study showed that 10h promotes epithelial-mesenchymal transition (EMT), migration, adhesion, invasion and trans-endothelial migration of mouse melanoma B16/F10 cells. We further demonstrated an increased tumour cell extravasation in the lungs of wild-type mice subjected to 10h treatment and in Pparβ/δ-/- mice in an experimental mouse model of blood-borne pulmonary metastasis by tail vein injection. This observation was further supported by an increased tumour burden in the lungs of Pparβ/δ-/- mice as demonstrated in the same animal model.
CONCLUSION: These results indicated a protective role of PPARβ/δ in melanoma progression and metastasis.

Matched MeSH terms: Melanoma/genetics*; Melanoma/pathology
Antimelanogenesis and Anti-Inflammatory Activity of Selected Culinary-Medicinal Mushrooms

Saad HM, Sim KS, Tan YS

Int J Med Mushrooms, 2018;20(2):141-153.
PMID: 29773006 DOI: 10.1615/IntJMedMushrooms.2018025463

Five culinary-medicinal mushrooms are commonly available in the Malaysian market: Agaricus bisporus (white and brown), Ganoderma lucidum, Hypsizygus marmoreus, Pleurotus floridanus, and P. pulmonarius. These species were selected for use in the current study, the aim of which was to investigate the antimelanogenesis and anti-inflammatory activity of these mushrooms in an attempt to evaluate their potential use in cosmeceuticals. Mushroom fruiting bodies were extracted with hot water, and the extracts were freeze-dried before testing. The antimelanogenesis activity of the extracts was determined by cell viability assay, measurement of intracellular melanin content, and cellular tyrosinase assay with B16F10 melanoma cells. The anti-inflammatory activity of the mushroom extracts was tested by measuring the levels of nitric oxide (NO), tumor necrosis factor (TNF)-α, and interleukin-10 excreted by RAW264.7 macrophages. Brown A. bisporus reduced intracellular melanin content to the largest extent-up to 57.05 ± 3.90%-without a cytotoxic effect on B16F10 melanoma cells. This extract also reduced cellular tyrosinase activity to 17.93 ± 2.65%, performing better than kojic acid, the positive control. In parallel, the extract from brown A. bisporus, at the highest concentration tested, has appreciable anti-inflammatory activity through reductions of NO and TNF-α levels. The other 5 extracts showed moderate antimelanogenesis and anti-inflammatory activities. In summary, our findings show that A. bisporus (brown) extract has the potential to be used as an ingredient in whitening skincare products and to sooth the inflammatory response on the skin.

Matched MeSH terms: Melanoma
Fulltext A lesion mistaken for malignant melanoma of the posterior uvea: a case report

Sukumaran K, Chandran S, Visvaraja S, Couper NT, Tan PE

Med J Malaysia, 1984 Dec;39(4):317-9.
PMID: 6544942

A case is presented to illustrate the difficulties
encountered in the clinical diagnosis of an intraocular mass. The fundus was not visible ophthalmoscopically because of opaque media. The anterior surface of the iris showed three discrete hyperpigmented nodular patches. Ultrasound showed an intraocular mass occupying half the posterior segment. The eye did not have useful vision and was enucleated after a clinical diagnosis of malignant melanoma of the choroid was made. The eye did not contain a melanoma but an organised blood clot after an extensive vitreous haemorrhage because of systemic hypertension.

Matched MeSH terms: Melanoma/diagnosis*
Fulltext Acral melanoma of the extremities: a study of 33 cases Sarawakian patients

Zainal AI, Zulkarnaen M, Norlida DK, Syed Alwi SA

Med J Malaysia, 2012 Feb;67(1):60-5.
PMID: 22582550

Acral melanoma involve the non-pigmented palmoplantar and subungual areas and are commonly seen among Asians. Patients commonly display advanced stage of disease at presentation. It may appear unnoticed and mimic benign lesions.

Matched MeSH terms: Melanoma/pathology*
Malignant melanomas in the Eur-African-Malay population of South Africa

Isaacson C, Spector I

Am J Dermatopathol, 1987 Apr;9(2):109-10.
PMID: 3504109

Malignant melanoma is common among the whites of South Africa. In the black population, the tumor is much less frequent and occurs predominantly on the lower limb--particularly the sole of the foot. This study brings to light the anomalous situation that among the Eur-African-Malay population (those of mixed ancestry), malignant melanoma has probably the lowest incidence in the world.

Matched MeSH terms: Melanoma/ethnology; Melanoma/epidemiology*
Amelanotic spitzoid melanoma in a prepubescent boy

Goh EH, Zarina AL, Thambidorai CR, Maizaton AA, Siti AM, Somasundram S

Pediatr Surg Int, 2008 Apr;24(4):447-9.
PMID: 17437116

The diagnosis of malignant melanoma (MM) in children is difficult due to its uncommon occurrence as well histological similarities to Spitz nevus. A case of MM of the foot in an 11-year-old boy is reported illustrating the histological overlap between Spitz nevus and MM. In our patient, both the primary foot lesion and the regional inguinal metastases were amelanotic, further increasing the diagnostic difficulty. The literature on MM in children is limited and the documentation of such unusual cases is necessary to improve the knowledge on this disease.

Matched MeSH terms: Melanoma, Amelanotic/pathology*; Melanoma, Amelanotic/secondary; Melanoma, Amelanotic/surgery
Fulltext Malignant melanoma of the foot in patients with diabetes mellitus--a trap for the unwary

Hussin P, Loke SC, Noor FM, Mawardi M, Singh VA

Med J Malaysia, 2012 Aug;67(4):422-3.
PMID: 23082455

Melanomas on the foot are difficult to differentiate from diabetic foot ulcers (DFU). In particular, acral lentiginous and amelanotic melanomas have a high chance of being misdiagnosed. We present two patients with diabetes mellitus and malignant melanomas of the foot initially diagnosed as DFU. Both cases were treated with wide excision amputation and local dissection, without adjuvant chemotherapy or radiotherapy. Both patients remain disease-free up to the last follow-up visit. It is important to maintain a high index of suspicion and a skin biopsy should be done in any DFU with atypical features.

Matched MeSH terms: Melanoma/complications; Melanoma/diagnosis*; Melanoma/surgery
Fulltext Bioactive Constituents of Zanthoxylum rhetsa Bark and Its Cytotoxic Potential against B16-F10 Melanoma Cancer and Normal Human Dermal Fibroblast (HDF) Cell Lines

Santhanam RK, Ahmad S, Abas F, Safinar Ismail I, Rukayadi Y, Tayyab Akhtar M, et al.

Molecules, 2016 May 24;21(6).
PMID: 27231889 DOI: 10.3390/molecules21060652

Zanthoxylum rhetsa is an aromatic tree, known vernacularly as "Indian Prickly Ash". It has been predominantly used by Indian tribes for the treatment of many infirmities like diabetes, inflammation, rheumatism, toothache and diarrhea. In this study, we identified major volatile constituents present in different solvent fractions of Z. rhetsa bark using GC-MS analysis and isolated two tetrahydrofuran lignans (yangambin and kobusin), a berberine alkaloid (columbamine) and a triterpenoid (lupeol) from the bioactive chloroform fraction. The solvent fractions and purified compounds were tested for their cytotoxic potential against human dermal fibroblasts (HDF) and mouse melanoma (B16-F10) cells, using the MTT assay. All the solvent fractions and purified compounds were found to be non-cytotoxic to HDF cells. However, the chloroform fraction and kobusin exhibited cytotoxic effect against B16-F10 melanoma cells. The presence of bioactive lignans and alkaloids were suggested to be responsible for the cytotoxic property of Z. rhetsa bark against B16-F10 cells.

Matched MeSH terms: Melanoma, Experimental/drug therapy*; Melanoma, Experimental/pathology
Fulltext Inhibition of MAPKs, Myc/Max, NFκB, and hypoxia pathways by Phyllanthus prevents proliferation, metastasis and angiogenesis in human melanoma (MeWo) cancer cell line

Tang YQ, Jaganath IB, Manikam R, Sekaran SD

Int J Med Sci, 2014;11(6):564-77.
PMID: 24782645 DOI: 10.7150/ijms.7704

Melanoma is the most fatal form of skin cancer. Different signalling pathways and proteins will be differentially expressed to pace with the tumour growth. Thus, these signalling molecules and proteins are become potential targets to halt the progression of cancer. The present works were attempted to investigate the underlying molecular mechanisms of anticancer effects of Phyllanthus (P.amarus, P.niruri, P.urinaria and P.watsonii) on skin melanoma, MeWo cells.

Matched MeSH terms: Melanoma/drug therapy; Melanoma/genetics; Melanoma/pathology*
Fulltext The anti-proliferative effects of a palm oil-derived product and its mode of actions in human malignant melanoma MeWo cells

Komarasamy TV, Sekaran SD

J Oleo Sci, 2012;61(4):227-39.
PMID: 22450124

Melanoma incidence and mortality have risen dramatically in recent years. No effective treatment for metastatic melanoma exists; hence currently, an intense effort for new drug evaluation is being carried out. In this study, we investigated the effects of a palm oil-derived nanopolymer called Bio-12 against human malignant melanoma. The nanopolymers of Bio-12 are lipid esters derived from a range of fatty acids of palm oil. Our study aims to identify the anti-proliferative properties of Bio-12 against human malignant melanoma cell line (MeWo) and to elucidate the mode of actions whereby Bio-12 brings about cell death. Bio-12 significantly inhibited the growth of MeWo cells in a concentration- and time- dependent manner with a median inhibitory concentration (IC₅₀) value of 1/25 dilution after 72 h but was ineffective on human normal skin fibroblasts (CCD-1059sk). We further investigated the mode of actions of Bio-12 on MeWo cells. Cell cycle flow cytometry demonstrated that MeWo cells treated with increasing concentrations of Bio-12 resulted in S-phase arrest, accompanied by the detection of sub-G1 content, indicative of apoptotic cell death. Induction of apoptosis was further confirmed via caspase (substrate) cleavage assay which showed induction of early apoptosis in MeWo cells. In addition, DNA strand breaks which are terminal event in apoptosis were evident through increase of TUNEL positive cells and formation of a characteristic DNA ladder on agarose gel electrophoresis. Moreover, treatment of MeWo cells with Bio-12 induced significant increase in lactate dehydrogenase (LDH) activity. These results show that Bio-12 possesses the ability to suppress proliferation of human malignant melanoma MeWo cells and this suppression is at least partly attributed to the initiation of the S-phase arrest, apoptosis and necrosis, suggesting that it is indeed worth for further investigations.

Matched MeSH terms: Melanoma/drug therapy*; Melanoma/metabolism
Fulltext Phyllanthus spp. induces selective growth inhibition of PC-3 and MeWo human cancer cells through modulation of cell cycle and induction of apoptosis

Tang YQ, Jaganath IB, Sekaran SD

PLoS One, 2010;5(9):e12644.
PMID: 20838625 DOI: 10.1371/journal.pone.0012644

Phyllanthus is a traditional medicinal plant that has been used in the treatment of many diseases including hepatitis and diabetes. The main aim of the present work was to investigate the potential cytotoxic effects of aqueous and methanolic extracts of four Phyllanthus species (P.amarus, P.niruri, P.urinaria and P.watsonii) against skin melanoma and prostate cancer cells.

Matched MeSH terms: Melanoma/drug therapy; Melanoma/physiopathology*
Fulltext Anti-proliferative property of porcupine bezoar extract on melanoma (A375)

Al’aina Yuhainis Firus Khan, Faizah Abdullah Asuhaimi, Tara Jalal, Hatim Abdullah Natto, Opeyemi Roheem, Fatimah, Qamar Uddin Ahmed, et al.

International Journal of Allied Health Sciences, 2017;1(2):1-13.
MyJurnal

Porcupine bezoar (PB) has been previously reported to possess various medicinal properties. However, its potential as an anticancer agent against human cancers is still poorly studied and understood. Hence, in this study, porcupine bezoar (PB) aqueous extract was evaluated for its potential as a safe anticancer agent. Initially PB was infused in water for 18 h to get PB aqueous extract which was preliminary tested for total phenolic content (TPC), total flavonoid content (TFC), DPPH activity in order to confirm the presence of bioactive agents as antioxidants in PB. Later, PB aqueous extract was subjected to A375 (Melanoma) (IC50, cell proliferation assay) and HGF-1
(normal cell, for cytotoxicity assay) to evaluate its anticancer potential. PB aqueous extract showed 11.68 μg/mL ± 0.67 TPC value expressed as gallic acid equivalents while TFC was not detected confirming the absence of flavonoids in PB aqueous extract. IC50 for DPPH was found to be 0.79 μg/mL ± 0.07. The IC50 result for A375 was found to be 10.1 µg/mL ± 0.17. PB aqueous extract showed significant antiproliferation pattern at 24, 48 and 72 hours exposures. The data from this study suggest the potential alternative use of PB in developing natural antioxidants and antiproliferative agents for improving human health.

Matched MeSH terms: Melanoma
Genotoxicity and apoptotic effect of silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(p-tolyl)phosphine on malignant melanoma cells, SK-MEL-28

Ooi TC, Nordin FJ, Rahmat NS, Abdul Halim SN', Sarip R, Chan KM, et al.

Mutat Res Genet Toxicol Environ Mutagen, 2023;886:503581.
PMID: 36868695 DOI: 10.1016/j.mrgentox.2022.503581

Complexes of coinage metals can potentially be used as alternatives to platinum-based chemotherapeutic drugs. Silver is a coinage metal that can potentially improve the spectrum of efficacy in various cancers treatment, such as malignant melanoma. Melanoma is the most aggressive form of skin cancer that is often diagnosed in young and middle-aged adults. Silver has high reactivity with skin proteins and can be developed as a malignant melanoma treatment modality. Therefore, this study aims to identify the anti-proliferative and genotoxic effects of silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(p-tolyl)phosphine ligands in the human melanoma SK-MEL-28 cell line. The anti-proliferative effects of a series of silver(I) complex compounds labelled as OHBT, DOHBT, BrOHBT, OHMBT, and BrOHMBT were evaluated on SK-MEL-28 cells by using the Sulforhodamine B assay. Then, DNA damage analysis was performed in a time-dependent manner (30 min, 1 h and 4 h) by using alkaline comet assay to investigate the genotoxicity of OHBT and BrOHMBT at their respective IC50 values. The mode of cell death was studied using Annexin V-FITC/PI flow cytometry assay. Our current findings demonstrated that all silver(I) complex compounds showed good anti-proliferative activity. The IC50 values of OHBT, DOHBT, BrOHBT, OHMBT, and BrOHMBT were 2.38 ± 0.3 μM, 2.70 ± 0.17 μM, 1.34 ± 0.22 μM, 2.82 ± 0.45 μM, and 0.64 ± 0.04 μM respectively. Then, DNA damage analysis showed that OHBT and BrOHMBT could induce DNA strand breaks in a time-dependent manner, with OHBT being more prominent than BrOHMBT. This effect was accompanied by apoptosis induction in SK-MEL-28, as evaluated using Annexin V-FITC/PI assay. In conclusion, silver(I) complexes with mixed-ligands of thiosemicarbazones and diphenyl(p-tolyl)phosphine exerted anti-proliferative activities by inhibiting cancer cell growth, inducing significant DNA damage and ultimately resulting in apoptosis.

Matched MeSH terms: Melanoma*
Primary Melanoma of the Third Metatarsal

Singh VA, Lim CY, Yan HC, Rahman NA

J Foot Ankle Surg, 2017 06 26;56(6):1292-1297.
PMID: 28659241 DOI: 10.1053/j.jfas.2017.05.005

Melanoma is a well-known malignant neoplasm of the skin, although it can also arise from other structures. Bone metastasis is not an uncommon event associated with melanoma, although primary osseous melanoma is very rare. In the present report, we describe a case of primary melanoma arising from the left third metatarsal in an adult male. The lesion was treated with surgical excision without adjunct chemotherapy, and recurrence developed approximately 12 months after the foot surgery. The patient died of the cancer 34 months after it had been identified. Primary melanoma arising in a metatarsal is rare, and we wished to highlight this unusual presentation.

Matched MeSH terms: Melanoma/pathology*; Melanoma/surgery*

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