https://nova.newcastle.edu.au/vital/access/ /manager/Index ${session.getAttribute("locale")} 5 It is not all about the alpha: elevated expression of p53β variants is associated with lower probability of survival in a retrospective melanoma cohort https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:53356 Wed 28 Feb 2024 15:24:08 AEDT ]]> Adjuvant Therapy of Nivolumab Combined with Ipilimumab Versus Nivolumab Alone in Patients with Resected Stage IIIB-D or Stage IV Melanoma (CheckMate 915) https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50584 Wed 28 Feb 2024 15:06:35 AEDT ]]> Monitoring patient response to pembrolizumab with peripheral blood exhaustion marker profiles https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44986 Wed 26 Oct 2022 15:06:56 AEDT ]]> Founder mutations for early onset melanoma as revealed by whole exome sequencing suggests that this is not associated with the increasing incidence of melanoma in Poland https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44984 CDKN2A-variants. A replication study using a set of 1,200 melanoma patient DNA samples and similarly large series of healthy controls was undertaken. Results: We selected 21 potentially deleterious variants in 20 genes (VRK1, MYCT1, DNAH14, CASC3, MS4A12, PRC1, WWOX, CARD6, EXO5, CASC3, CASP8AP2, STK33, SAMD11, CNDP2, CPNE1, EFCAB6, CABLES1, LEKR1, NUDT17, and RRP15), which were identified by WES and confirmed by Sanger sequencing for an association study. Evaluation of the allele distribution among carriers and their relatives in available family trios revealed that these variants were unlikely to account for many familial cases of melanoma. Replication study revealed no statistically significant differences between cases and controls. Conclusion: Although most of the changes seemed to be neutral we could not exclude an association between variants in VRK1, CREB3L3, EXO5, and STK33 with melanoma risk.]]> Wed 26 Oct 2022 09:22:11 AEDT ]]> Identification of the NR2C subtype of the N-Methyl-D-Aspartate Receptor (NMDAR) as a potential molecular target for melanoma treatment https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37717 Wed 24 Mar 2021 16:17:33 AEDT ]]> ACTN4 regulates the stability of RIPK1 in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:37515 Wed 23 Aug 2023 09:36:21 AEST ]]> BRAF/MEK inhibitors promote CD47 expression that is reversible by ERK inhibition in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30575 Wed 20 Mar 2019 12:05:15 AEDT ]]> Implication of unfolded protein response and autophagy in the treatment of BRAF inhibitor resistant melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28828 V600E mutation, is one of the key alterations in melanoma. Accordingly, two BRAF inhibitors (BRAFi), vemurafenib and dabrafenib are utilized to treat melanoma and resulted in an excellent clinical outcome. However, the clinical success is not long-lasting, and the BRAFi resistance and disease progression inevitably occurs in nearly all patients. Endoplasmic reticulum stress-induced unfolded protein response and autophagy have emerged as potential pro-survival mechanisms adopted by melanoma cells in response to BRAFi. In this review, we discuss the role of unfolded protein response and autophagy that are implicated in the development of BRAFi-resistant melanoma and the corresponding strategy aiming at overcoming the intractable clinical problem.]]> Wed 19 Jan 2022 15:18:22 AEDT ]]> Histone deacetylases (HDACs) as mediators of resistance to apoptosis in melanoma and as targets for combination therapy with selective BRAF inhibitors https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27649 Wed 17 May 2017 11:47:32 AEST ]]> Silica-based nanomaterials as drug delivery tools for skin cancer (melanoma) treatment https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39596 Wed 15 Jun 2022 12:47:16 AEST ]]> AEBP1 upregulation confers acquired resistance to BRAF (V600E) inhibition in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14360 Wed 11 Apr 2018 17:15:26 AEST ]]> Suppression of PP2A is critical for protection of melanoma cells upon endoplasmic reticulum stress https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21727 EL by protein phosphatase 2A (PP2A). However, melanoma cells are largely resistant to ER stress-induced apoptosis, suggesting that Bim activation is suppressed in melanoma cells undergoing ER stress. We show here that ER stress reduces PP2A activity leading to increased ERK activation and subsequent phosphorylation and proteasomal degradation of BimEL. Despite sustained upregulation of Bim at the transcriptional level, the BimEL protein expression was downregulated after an initial increase in melanoma cells subjected to pharmacological ER stress. This was mediated by increased activity of ERK, whereas the phosphatase activity of PP2A was reduced by ER stress in melanoma cells. The increase in ERK activation was, at least in part, due to reduced dephosphorylation by PP2A, which was associated with downregulation of the PP2A catalytic C subunit. Notably, instead of direct dephosphorylation of BimEL, PP2A inhibited its phosphorylation indirectly through dephosphorylation of ERK in melanoma cells. Taken together, these results identify downregualtion of PP2A activity as an important protective mechanism of melanoma cells against ER stress-induced apoptosis.]]> Wed 11 Apr 2018 17:12:53 AEST ]]> Cotargeting histone deacetylases and oncogenic BRAF synergistically kills human melanoma cells by necrosis independently of RIPK1 and RIPK3 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14354 V600E melanoma cells by induction of necrosis. Cotreatment with the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) or panobinostat (LBH589) and the BRAF inhibitor PLX4720 activated the caspase cascade, but caspases appeared dispensable for killing, in that inhibition of caspases did not invariably block induction of cell death. The majority of dying cells acquired propidium iodide positivity instantly when they became positive for Annexin V, suggesting induction of necrosis. This was supported by caspase-independent release of high-mobility group protein B1, and further consolidated by rupture of the plasma membrane and loss of nuclear and cytoplasmic contents, as manifested by transmission electron microscopic analysis. Of note, neither the necrosis inhibitor necrostatin-1 nor the small interference RNA (siRNA) knockdown of receptor-interacting protein kinase 3 (RIPK3) inhibited cell death, suggesting that RIPK1 and RIPK3 do not contribute to induction of necrosis by combinations of HDAC and BRAF inhibitors in BRAFV600E melanoma cells. Significantly, SAHA and the clinically available BRAF inhibitor vemurafenib cooperatively inhibited BRAFV600E melanoma xenograft growth in a mouse model even when caspase-3 was inhibited. Taken together, these results indicate that cotreatment with HDAC and BRAF inhibitors can bypass canonical cell death pathways to kill melanoma cells, which may be of therapeutic advantage in the treatment of melanoma.]]> Wed 11 Apr 2018 17:05:48 AEST ]]> Macrophage migration inhibitory factor engages PI3K/Akt signalling and is a prognostic factor in metastatic melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20455 Wed 11 Apr 2018 16:49:10 AEST ]]> Examining the expression of nucleotide excision repair genes in melanoma tumours https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27892 Wed 11 Apr 2018 16:44:14 AEST ]]> Noxa upregulation by oncogenic activation of MEK/ERK through CREB promotes autophagy in human melanoma cells https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19023 V600E or MEK downregulated Noxa, whereas activation of MEK/ERK caused its upregulation. In addition, introduction of BRAFV600E increased Noxa expression in melanocytes. Upregulation of Noxa was due to a transcriptional increase mediated by cAMP responsive element binding protein, activation of which was also increased by MEK/ERK signaling in melanoma cells. Significantly, Noxa appeared necessary for constitutive activation of autophagy, albeit at low levels, by MEK/ERK in melanoma cells. Furthermore, it was required for autophagy activation that delayed apoptosis in melanoma cells undergoing nutrient deprivation. These results reveal that oncogenic activation of MEK/ERK drives Noxa expression to promote autophagy, and suggest that Noxa has an indirect anti-apoptosis role in melanoma cells under nutrient starvation conditions.]]> Wed 11 Apr 2018 16:41:25 AEST ]]> Checkpoint immunotherapy for cancer: superior survival, unaccustomed toxicities https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27041 Wed 11 Apr 2018 16:32:14 AEST ]]> Regulation of apoptosis induced by targeting the RAF/MEK/ERK pathway in human melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15254 Wed 11 Apr 2018 16:23:04 AEST ]]> Inositol polyphosphate 4-phosphatase II (INPP4B) promotes P13K signalling and functions as an oncogenic regulator in human colon cancer and melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:16707 Wed 11 Apr 2018 16:05:23 AEST ]]> Evidence for upregulation of Bim and the splicing factor SRp55 in melanoma cells from patients treated with selective BRAF inhibitors https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15167 Wed 11 Apr 2018 16:01:18 AEST ]]> Regulators of global genome repair do not respond to DNA damaging therapy but correlate with survival in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14356 Wed 11 Apr 2018 15:41:30 AEST ]]> Survival in BRAF V600-mutant advanced melanoma treated with vemurafenib https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28543 Wed 11 Apr 2018 15:37:28 AEST ]]> Oncolysis of malignant human melanoma tumors by Coxsackieviruses A13, A15 and A18 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15677 Wed 11 Apr 2018 15:24:49 AEST ]]> TRIM16 inhibits proliferation and migration through regulation of interferon beta 1 in melanoma cells https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:18837 Wed 11 Apr 2018 15:08:53 AEST ]]> Safety and tumor responses with lambrolizumab (anti-PD-1) in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14865 Wed 11 Apr 2018 14:49:29 AEST ]]> Loss of PI(4,5)P₂ 5-phosphatase A contributes to resistance of human melanoma cells to RAF/MEK inhibitors https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14384 V600E and by the MEK inhibitor U0126 in both BRAFV600E and wild-type BRAF melanoma cells. This was due to inhibition of PI3K/Akt, as co-introduction of an active form of Akt (myr-Akt) abolished the effect of overexpression of PIB5PA on apoptosis induced by PLX4720 or U0126. While overexpression of PIB5PA triggered activation of Bad and down-regulation of Mcl-1, knockdown of Bad or overexpression of Mcl-1 recapitulated, at least in part, the effect of myr-Akt, suggesting that regulation of Bad and Mcl-1 is involved in PIB5PA-mediated sensitization of melanoma cells to the inhibitors. The role of PIB5PA deficiency in BRAF inhibitor resistance was confirmed by knockdown of PIB5PA, which led to increased growth of BRAFV600E melanoma cells selected for resistance to PLX4720. Consistent with its role in vitro, overexpression of PIB5PA and the MEK inhibitor selumetinib cooperatively inhibited melanoma tumor growth in a xenograft model. Taken together, these results identify loss of PIB5PA as a novel resistance mechanism of melanoma to RAF/MEK inhibitors and suggest that restoration of PIB5PA may be a useful strategy to improve the therapeutic efficacy of the inhibitors in the treatment of melanoma.]]> Wed 11 Apr 2018 14:44:27 AEST ]]> Apoptosis of human melanoma cells induced by inhibition of B-RAFᵛ⁶⁰⁰ᴱ involves preferential splicing of bimS https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:9452 Wed 11 Apr 2018 14:22:54 AEST ]]> OBATOCLAX and ABT-737 induce ER stress responses in human melanoma cells that limit induction of apoptosis https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14361 Wed 11 Apr 2018 13:27:51 AEST ]]> Repression of microRNA-768-3p by MEK/ERK signalling contributes to enhanced mRNA translation in human melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17254 V600E melanoma cells with the mutant BRAF inhibitor PLX4720 or exposure of either BRAFV600E or wild-type BRAF melanoma cells to the MEK inhibitor U0126 resulted in the upregulation of miR-768-3p and inhibition of nascent protein synthesis. This inhibition was partially blocked in cells cointroduced with anti-miR-768-3p. Significantly, miR-768-3p was similarly downregulated, which was inversely associated with the expression levels of eIF4E in fresh melanoma isolates. Taken together, these results identify downregulation of miR-768-3p and subsequent upregulation of eIF4E as an important mechanism in addition to phosphorylation of eIF4E responsible for MEK/ERK-mediated enhancement of protein synthesis in melanoma.]]> Wed 11 Apr 2018 13:07:32 AEST ]]> Enhancement of oncolytic coxasckievirus A21 with conventional chemotherapies and immune checkpoint inhibitors for the treatment of melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22457 Wed 11 Apr 2018 12:54:57 AEST ]]> The role of altered nucleotide excision repair and UVB-induced DNA damage in melanomagenesis https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12520 Wed 11 Apr 2018 12:41:53 AEST ]]> RIPK1 regulates survival of human melanoma cells upon endoplasmic reticulum stress through autophagy https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28314 Wed 11 Apr 2018 12:40:55 AEST ]]> Whole brain radiotherapy after local treatment of brain metastases in melanoma patients - a randomised phase III trial https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15470 Wed 11 Apr 2018 12:20:10 AEST ]]> A clinicopathological review of 33 patients with vulvar melanoma identifies c-KIT as a prognostic marker https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:18034 1 cm, and e) c-KIT expression as valuable prognostic predictors for disease-free survival. We conclude that c-KIT expression is, apart from Breslow's depth, another valuable predictor of prognosis and survival. Lichen sclerosus may be associated with vulvar melanoma.]]> Wed 11 Apr 2018 12:14:22 AEST ]]> The role of nucleotide excision repair in melanoma development and platinum chemotherapy resistance https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27882 Wed 11 Apr 2018 12:08:33 AEST ]]> Patterns of response to anti-PD-1 treatment: an exploratory comparison of four radiological response criteria and associations with overall survival in metastatic melanoma patients https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29771 P<0.0001). Delayed response post first scan was seen in 2 out of 37 (5%) deemed progressive (PD) by RECIST and 2 out of 14 (14%) deemed PD by irRC. Modified CHOI criteria showed response of 38% (14 out of 37). Change in tumour size and density on first follow-up assessment was associated with OS with each 1000 mm2 increase in tumour size from baseline increasing the hazard of dying by 25.9% (HR=1.259, (95% CI=1.116-1.420), P=0.0002). Similarly, each 20HU increase in density increased the HR by 15% (HR=1.15, (95% CI 1.045-1.260), P=0.004). Response defined by any criteria had superior OS (CHOI P=0.0084; mCHOI P=0.0183; irRC P<0.0001 and RECIST P=0.0003). Conclusions: Response by any criterion was prognostic. Novel patterns of response and changes on treatment in tumour density suggest complex anti-tumour responses to immunotherapy.]]> Wed 11 Apr 2018 12:06:49 AEST ]]> Real-world efficacy, toxicity and clinical management of ipilimumab treatment in metastatic melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:30091 Wed 11 Apr 2018 12:04:08 AEST ]]> Targeting adaptative mechanisms to endoplasmic reticulum stress in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14172 Wed 11 Apr 2018 11:56:01 AEST ]]> Cancer biomarker discovery: the entropic hallmark https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:9568 Wed 11 Apr 2018 11:52:59 AEST ]]> PI(4,5)P2 5-phosphatase A regulates PI3K/Akt signalling and has a tumour suppressive role in human melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14353 Wed 11 Apr 2018 11:50:58 AEST ]]> Expression of the uncharacterised isoform, BCL2β, in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27441 Wed 11 Apr 2018 11:10:42 AEST ]]> Dual processing of FAT1 cadherin protein by human melanoma cells generates distinct protein products https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:9196 Wed 11 Apr 2018 10:54:31 AEST ]]> Oncogenic suppression of PHLPP1 in human melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17266 Wed 11 Apr 2018 10:51:24 AEST ]]> Nucleotide excision repair of UVA-induced DNA damage: regulation in sunlight-induced melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21077 Wed 11 Apr 2018 10:47:55 AEST ]]> Sensitising human melanoma cells to TRAIL-induced apoptosis https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:12634 Wed 11 Apr 2018 10:45:58 AEST ]]> Insulin induces drug resistance in melanoma through activation of the PI3K/Akt pathway https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:14871 Wed 11 Apr 2018 10:34:19 AEST ]]> The effects of PIB5PA on migration and invasion of human melanoma cells https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20768 P < 0.05), and reduced the expression levels of p-AKT, p-FAK, MMP-2, MMP-9, TIMP-1, TIMP-2, MMP-2/ TIMP-2 and MMP-9/TIMP-1 proteins (all P < 0.05). Conclusion: Over-expression of PIB5PA can inhibit the abilities of migration and invasion of human melanoma Mel-FH cells in vitro , which may be associated with inactivity of AKT and FAK, and down-regulation of the relative expression levels of MMP-2/TIMP-2 and MMP-9/TIMP-1.]]> Wed 11 Apr 2018 10:29:22 AEST ]]> Somatic copy number amplification and hyperactivating somatic mutations of EZH2 correlate with DNA methylation and drive epigenetic silencing of genes involved in tumor suppression and immune responses in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29412 Wed 11 Apr 2018 09:50:06 AEST ]]> INPP4B is upregulated and functions as an oncogenic driver through SGK3 in a subset of melanomas https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22865 Wed 11 Apr 2018 09:31:09 AEST ]]> Sequential decitabine and carboplatin treatment increases the DNA repair protein XPC, increases apoptosis and decreases proliferation in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32798 Wed 09 Mar 2022 16:01:33 AEDT ]]> Nucleotide excision repair deficiency in melanoma in response to UVA https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:24616 40 % of lesions remained in melanoma cell lines at 48 h. This was coupled with a delayed and reduced induction of GGR component XPC in melanoma cells, independent of p53. Conclusion: These findings support that NER activity is reduced in melanoma cells due to deficient GGR. Further investigation into the role of NER in UVA-induced melanomagenesis is warranted and may have implications for melanoma treatment.]]> Wed 09 Feb 2022 15:53:41 AEDT ]]> Cylindromatosis is required for survival of a subset of melanoma cells https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:39074 Wed 04 May 2022 15:24:42 AEST ]]> Repair of UVB-induced DNA damage is reduced in melanoma due to low XPC and global genome repair https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:27853 T transitions. These mutations are found throughout the melanoma genome, particularly in non-transcribed regions. The global genome repair (GGR) branch of nucleotide excision repair (NER) is responsible for repairing UV-induced DNA damage across non-transcribed and silent regions of the genome. This study aimed to examine the relationship between UVB and GGR in melanoma. DNA repair capacity and relative expression of NER in melanocytes and melanoma cell lines before and after treatment with UVB was quantified. Transcript expression from 196 melanomas was compared to clinical parameters including solar elastosis and whole transcriptome data collected. Melanoma cell lines showed significantly reduced DNA repair when compared to melanocytes, most significantly in the S phase of the cell cycle. Expression of GGR components XPC, DDB1 and DDB2 was significantly lower in melanoma after UVB. In the melanoma tumours, XPC expression correlated with age of diagnosis and low XPC conferred significantly poorer survival. The same trend was seen in the TCGA melanoma dataset. Reduced GGR in melanoma may contribute to the UV mutation spectrum of the melanoma genome and adds further to the growing evidence of the link between UV, NER and melanoma.]]> Wed 02 Mar 2022 14:27:55 AEDT ]]> Confocal microscopy, dermoscopy, and histopathology features of atypical intraepidermal melanocytic proliferations associated with evolution to melanoma in situ https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:44783 Tue 30 Apr 2024 09:05:42 AEST ]]> Constitutional variants in POT1, TERF2IP, and ACDgenes in patients with melanoma in the Polish population https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:38900 POT1, ACD, and TERF2IP mutations among Polish melanoma patients. A cohort of 60 patients from melanoma-prone families, 1500 unselected cases and 1500 controls were genotyped. Methodology included Sanger sequencing, in-silico software predilection, and TaqMan assays. We identified three nonsynonymous variants: POT1 c.903 G>T; TERF2IP c.970 A>G; and ACD c.1544 T>C and a splice site variant ACD c.645 G>A. The c.903 G>T was predicted to be pathogenic according to PolyPhen-2, benign according to Mutation Taster, PROVEAN, AGVGD, and SIFT. The c.645 G>A was defined as disease caused by Mutation Taster and Human Splicing Finder and as variant of unknown significance by ClinVar. The other detected variants were described as benign. The c.903 G>T variant was present in two unselected cases and one control [P = 0.57, odds ratio (OR) = 2.00]; the c.645 G>A variant was not detected among the unselected cases and the controls; the c.970 A>G variant was present in 110 cases and 133 controls (P = 0.14, OR = 0.81); the c.1544 T>C variant was present in 687 cases and 642 controls (P = 0.11, OR = 1.07). We found no loss of heterozygosity of the c.903 G>T, c.970 A>G, and c.645 G>A variants. C.645 G>A variant had no effect on splicing or expression. The changes in POT1 c.903 G>T and ACD c.645 G>A can be classified as rare variants of unknown significance, the other variants appear to be polymorphisms. Germline mutations in POT1, ACD, and TERF2IP are infrequent among Polish melanoma patients.]]> Tue 01 Mar 2022 16:02:13 AEDT ]]> Intralesional PV-10 for the treatment of in-transit melanoma metastases - results of a prospective, non-randomized, single center study https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:35010 Thu 30 May 2019 14:51:49 AEST ]]> A novel compound which sensitizes BRAF wild-type melanoma cells to vemurafenib in a TRIM16-dependent manner https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25129 V600E/K mutation. In melanoma cells, loss of TRIM16 expression is a marker of cell migration and metastasis, while the BRAF inhibitor, vemurafenib, induces melanoma cell growth arrest in a TRIM16-dependent manner. Here we identify a novel small molecule compound which sensitized BRAF wild-type melanoma cells to vemurafenib. High throughput, cell-based, chemical library screening identified a compound (C012) which significantly reduced melanoma cell viability, with limited toxicity for normal human fibroblasts. When combined with the BRAFV600E/K inhibitor, vemurafenib, C012 synergistically increased vemurafenib potency in 5 BRAFWT and 4 out of 5 BRAFV600E human melanoma cell lines (Combination Index: CI < 1), and, dramatically reduced colony forming ability. In addition, this drug combination was significantly anti-tumorigenic in vivo in a melanoma xenograft mouse model. The combination of vemurafenib and C012 markedly increased expression of TRIM16 protein, and knockdown of TRIM16 significantly reduced the growth inhibitory effects of the vemurafenib and C012 combination. These findings suggest that the combination of C012 and vemurafenib may have therapeutic potential for the treatment of melanoma, and, that reactivation of TRIM16 may be an effective strategy for patients with this disease.]]> Thu 28 Oct 2021 12:37:19 AEDT ]]> The regenerating naevus https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29180 Thu 24 Mar 2022 11:30:18 AEDT ]]> The double life of RIPK1 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:50344 Thu 20 Jul 2023 14:26:55 AEST ]]> BRAF/MEK inhibitors promote CD47 expression that is reversible by ERK inhibition in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:32504 Thu 14 Apr 2022 10:59:36 AEST ]]> Immunotherapy-induced sarcoidosis in patients with melanoma treated with PD-1 checkpoint inhibitors: Case series and immunophenotypic analysis https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:34826 Thu 13 Jan 2022 10:31:11 AEDT ]]> Repurposing azacitidine and carboplatin to prime immune checkpoint blockade-resistant melanoma for anti-PD-L1 re-challenge https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:49310 Thu 11 May 2023 14:39:28 AEST ]]> Metastatic melanoma treatment: combining old and new therapies https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29594 Thu 03 Feb 2022 12:21:03 AEDT ]]> Melanoma: An immunotherapy journey from bench to bedside https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48125 Thu 02 Mar 2023 15:06:34 AEDT ]]> The emerging important role of microRNAs in the pathogenesis, diagnosis and treatment of human cancers https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:15221 Sat 24 Mar 2018 08:26:08 AEDT ]]> Developing chemotherapeutics which disable the actin cytoskeleton of melanoma cells https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13243 Sat 24 Mar 2018 08:17:36 AEDT ]]> Targeting anti-apoptotic mechanisms for reversal of resistance to BRAF inhibitors in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13255 Sat 24 Mar 2018 08:16:00 AEDT ]]> BRAF and NRAS mutational status are prognostically important in thick and locally advanced cutaneous melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13259 Sat 24 Mar 2018 08:15:59 AEDT ]]> CAVATAK (Coxsackievirus A21) displays potent oncolytic activity in BRAFV600E mutant melanoma cells resistant to selective BRAF kinase inhibitors https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13251 Sat 24 Mar 2018 08:15:58 AEDT ]]> Phosphatidylinositol 4,5-Bisphosphate 5-Phosphatase A regulates PI3K/Akt signaling in human melanoma cells https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13253 Sat 24 Mar 2018 08:15:58 AEDT ]]> Exploratory consensus of hierarchical clusterings for melanoma and breast cancer https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:10125 Sat 24 Mar 2018 08:13:41 AEDT ]]> Cystatin B inhibition of TRAIL-induced apoptosis is associated with the protection of FLIPL from degradation by the E3 ligase itch in human melanoma cells https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:10550 Sat 24 Mar 2018 08:10:18 AEDT ]]> Prevalence of the E318K and V320I MITF germline mutations in Polish cancer patients and multiorgan cancer risk-a population-based study https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20712 Sat 24 Mar 2018 08:06:21 AEDT ]]> Adipocytes contribute to resistance of human melanoma cells to chemotherapy and targeted therapy https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21445 Sat 24 Mar 2018 08:05:44 AEDT ]]> Sustained IRE1 and ATF6 signaling is important for survival of melanoma cells undergoing ER stress https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:21386 Sat 24 Mar 2018 08:05:03 AEDT ]]> Oncogenic suppression of PHLPP1 in human melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17503 Sat 24 Mar 2018 08:04:05 AEDT ]]> Methoxyphenylcipro induces antitumor activity in human cancer cells https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17312 Sat 24 Mar 2018 08:01:52 AEDT ]]> Obesity and melanoma: exploring molecular links https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:18436 Sat 24 Mar 2018 07:59:47 AEDT ]]> A narrative review of the potential for self- tanning products to substitute for solaria use among people seeking a tanned appearance https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:18466 Sat 24 Mar 2018 07:59:43 AEDT ]]> Modulation of NOXA and MCL-1 as a strategy for sensitizing melanoma cells to the BH3-mimetic ABT-737 https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20878 Sat 24 Mar 2018 07:57:56 AEDT ]]> Ets-1 mediates upregulation of Mcl-1 downstream of XBP-1 in human melanoma cells upon ER stress https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:17732 Sat 24 Mar 2018 07:57:44 AEDT ]]> Targeted therapy in melanoma: the era of personalized medicine https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:19810 Sat 24 Mar 2018 07:57:12 AEDT ]]> Side effects and toxicities of targeted therapies in stage IV melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:20976 Sat 24 Mar 2018 07:54:20 AEDT ]]> ER stress-induced autophagy in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:28082 Sat 24 Mar 2018 07:39:48 AEDT ]]> Evaluation of immune-related response criteria and RECIST v1.1 in patients with advanced melanoma treated with pembrolizumab https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29413 Sat 24 Mar 2018 07:36:21 AEDT ]]> Programmed death-ligand 1 expression and response to the anti-programmed death 1 antibody pembrolizumab in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29414 Sat 24 Mar 2018 07:36:12 AEDT ]]> Targeting apoptotic pathways in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:25800 Sat 24 Mar 2018 07:34:44 AEDT ]]> Association of pembrolizumab with tumor response and survival among patients with advanced melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29369 Sat 24 Mar 2018 07:34:17 AEDT ]]> EZH2 as a mediator of treatment resistance in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:29370 Sat 24 Mar 2018 07:34:17 AEDT ]]> RIP1 kinase is an oncogenic driver in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:26954 Sat 24 Mar 2018 07:27:01 AEDT ]]> Melanoma early detection and awareness: how countries developing melanoma awareness programs could benefit from melanoma-proficient countries https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:22175 Sat 24 Mar 2018 07:14:58 AEDT ]]> The melanoma-associated antigen MAGE-D2 suppresses TRAIL receptor 2 and protects against TRAIL-induced apoptosis in human melanoma cells https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:23422 Sat 24 Mar 2018 07:13:54 AEDT ]]> Actin crosslinking protein α-actinin-4 (ACTN4) regulates receptor-interacting serine/threonine-protein kinase 1 (RIPK1) in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:33913 Mon 23 Sep 2019 10:51:36 AEST ]]> Expression of NGF/proNGF and Their Receptors TrkA, p75<sup>NTR</sup> and Sortilin in Melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:51398 Mon 04 Sep 2023 14:57:50 AEST ]]> Anti-PD-1-induced high-grade hepatitis associated with corticosteroid-resistant T cells: a case report https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48634 3.5-fold after steroid and ATG treatment. This case illustrates the need to consider this form of steroid resistance in patients failing treatment with corticosteroids. It also highlights the need for both better identification of patients at risk and the development of treatments that involve more specific immune suppression.]]> Mon 03 Apr 2023 10:14:28 AEST ]]> A systematic review and meta-analysis of locoregional treatments for in-transit melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:45488 Fri 28 Oct 2022 14:57:09 AEDT ]]> MC1R CpG island regulates MC1R expression and is methylated in a subset of melanoma tumours https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:48085 Fri 24 Feb 2023 14:56:04 AEDT ]]> BRCA1/2 mutations are not a common cause of malignant melanoma in the Polish population https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:42998 A and c.4534 C>T. Disease allele frequency was evaluated by genotyping of 1230 consecutive melanoma cases, 5000 breast cancer patients, 3500 prostate cancers and 9900 controls. Both variants were found to be absent among unselected cancer patients and healthy controls. The MutationTaster, Polyphen2 and SIFT algorithms indicate that c.9334G>A is a damaging variant. Due to lack of tumour tissue LOH analysis could not be performed for this variant. The variant segregated with the disease. The c.4534 C>T variant did not segregate with disease, there was no LOH of the variant. The c.9334G>A variant, classified as a rare variant of unknown significance, on current evidence may predisposes to cancers of the breast, prostate and melanoma. Functional studies to describe how the DNA change affects the protein function and a large multi-center study to evaluate its penetrance are required. © 2018 DeÎbniak et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.]]> Fri 09 Sep 2022 14:03:47 AEST ]]> Activating kinase mutations in melanoma https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:13257 Fri 07 Dec 2018 16:28:48 AEDT ]]> RIP1 protects melanoma cells from apoptosis induced by BRAF/MEK inhibitors https://nova.newcastle.edu.au/vital/access/ /manager/Repository/uon:36768 Fri 03 Jul 2020 14:41:43 AEST ]]>