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Effect of Omomyc on lymph node metastases from melanomas [SkMel147]

ABSTRACT: Skin melanomas are highly aggressive and metastatic. Omomyc is the best MYC inhibitor currently available. We analysed the effect of Omomyc expression in a transgenic and inducible (upon Doxycycline addition) manner in spontaneous lymph node metastases from SkMel147 (mutated in NRAS) melanoma cells in vivo. We used microarrays to detail the change in the gene expression programs induced by Omomyc on day 2.

ORGANISM(S): Homo sapiens

PROVIDER: GSE227843 | GEO | 2023/04/09

REPOSITORIES: GEO

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Effect of Omomyc on the in vivo growth of melanomas

Project description:Skin melanomas are highly aggressive and metastatic. Omomyc is the best MYC inhibitor currently available. We analysed the effect of Omomyc expression in a transgenic and inducible (upon Doxycycline addition) manner in melanoma cells in vivo in two different melanoma cell lines: A375 (mutated in BRAF), SkMel147 (mutated in NRAS). We used microarrays to detail the change in the gene expression programs induced by Omomyc on day 7.

2023-04-09 | GSE227841 | GEO

Effect of Omomyc on the in vivo growth of melanomas [SkMel147]

2023-04-09 | GSE227842 | GEO

Effect of Omomyc on lymph node metastases from melanomas [SkMel147]

Project description:Effect of Omomyc on lymph node metastases from melanomas [SkMel147]

| PRJNA947163 | ENA

Effect of Omomyc on the in vitro growth of A375 human melanoma cell line

Project description:Skin melanomas are highly aggressive and metastatic. Omomyc is the best MYC inhibitor currently available. We analysed the effect of Omomyc expression in a transgenic and inducible (upon Doxycycline addition) manner in melanoma cells in vitro in A375 (mutated in BRAF) melanoma cell line. We used microarrays to detail the change in the gene expression programs induced by Omomyc on day 4.

2023-04-09 | GSE227840 | GEO

Effect of Omomyc on the in vivo growth of melanomas

Project description:Effect of Omomyc on the in vivo growth of melanomas

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Effect of Omomyc on the in vivo growth of melanomas [SkMel147]

Project description:Effect of Omomyc on the in vivo growth of melanomas [SkMel147]

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BRAF activation by metabolic stress promotes glycolysis and survival, sensitizing NRASQ61 mutated melanomas to targeted therapy.

Project description:NRAS-mutated melanoma lacks an approved first-line treatment. Metabolic reprogramming is considered a novel target to control cancer; however, it is mostly unknow how the NRAS oncogene contributes to this cancer hallmark. Here, we show that NRASQ61-mutated melanomas harbor specific metabolic alterations that render cells sensitive to sorafenib upon metabolic stress. Mechanistically, these cells seem to depend on glucose metabolism, as glucose deprivation promotes the switch of the RAF isoform used from CRAF to BRAF. This process contributes to cell survival and sustains glucose metabolism through the phosphorylation of 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2/6- phosphofructo-2-kinase/fructose-2,6-bisphosph 3 (PFKFB2/PFKFB3) heterodimers by BRAF. In turn, this phosphorylation favors the allosteric activation of phosphofructokinase-1 (PFK1), generating a feedback loop linking glycolysis and the RAS signaling pathway. In vivo treatment of NRASQ61 mutant melanomas, including patient-derived xenografts, with the combination of 2-deoxy-D-glucose (2-DG) and sorafenib effectively inhibits tumor growth. Thus, we provide evidence of the contributions of NRAS oncogenes to metabolic rewiring and proof of principle for the treatment of NRAS-mutated melanoma with combinations of metabolic stress (glycolysis inhibitors) and already approved drugs such as sorafenib.

2023-01-09 | PXD028297 | Pride

Whole transcriptome analysis of T11 treated with FPP-1746-Omomyc

Project description:RNA Sequencing of claudin-low triple negative breast cancer cells T11 treated with FPP-1746-Omomyc, Omomyc, FPP-1746 and vehicle control (PBS) to determine differentially regulated genes induced by FPP-1746-Omomyc

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Individualized surgery: gamma-probe-guided lymphadenectomy in patients with clinically enlarged lymph node metastases from melanomas.

Project description:The value of a preoperative lymphoscintigraphy in melanoma patients with clinically evident regional lymph node metastases has not been studied. Therapeutic lymph node dissection (TLND) is regarded as the clinical standard, but the appropriate extent of TLND is controversial in all lymphatic basins.Of the 115 consecutive patients with surgery on palpable lymph node metastases, 34 received a pre-operative lymphoscintigraphy. Lymphatic drainage to a second nodal basin outside the clinically involved basin was found in 15 cases. In 13 patients, the ectopic tumor-draining lymph nodes were excised as in a sentinel node biopsy. The lymph nodes from the TLND specimens were postoperatively separated and classified as either radioactive or non-radioactive.A total of 493 lymph nodes were examined pathologically. The largest macrometastasis maintained the ability to take up radiotracer in 77% of cases. Radioactively labeled lymph nodes carried a higher risk of being involved with metastasis. The proportions of tumor involvement for radioactive and non-radioactive lymph nodes were 44.5 and 16.9%, respectively (P=0.00002). Of the 13 ectopic nodal basins surgically explored, six harbored clinically occult metastases.In patients undergoing TLND for palpable metastases, tumor-draining lymph nodes in a second, ectopic nodal basin should be excised, because they could be affected by occult metastasis. With respect to radioactive lymph nodes situated within the nodal basin of the macrometastasis but beyond the borders of a less-radical lymphadenectomy, further studies are needed.

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Deep Inguinal Lymph Node Metastases Can Predict Pelvic Lymph Node Metastases and Prognosis in Penile Squamous Cell Carcinoma.

Project description:ObjectivesTo evaluate the relationship between deep inguinal lymph node metastasis (ILNM) and pelvic lymph node metastasis (PLNM) and explore the prognostic value of deep ILNM in penile squamous cell carcinoma (PSCC).Materials and methodsThe records of 189 patients with ILNM treated for PSCC were analysed retrospectively. Logistic regression models were used to test for predictors of PLNM. Cox regression was performed in univariable and multivariable analyses of cancer-specific survival (CSS). CSS was compared using Kaplan-Meier analyses and log rank tests.ResultsPLNM were observed in 53 cases (28.0%). According to logistic regression models, only deep ILNM (OR 9.72, p<0.001) and number (≥3) of metastatic inguinal lymph nodes (ILNs) (OR 2.36, p=0.03) were independent predictors of PLNM. The incidences of PLNM were 18% and 19% with negative deep ILNM and extranodal extension (ENE); and 76% and 42% with positive deep ILNM and ENE, respectively. The accuracy of deep ILNM, ENE, bilateral involvement and number (≥3) of ILNMs for predicting PLNM were 81.0%, 65.6%, 63.5% and 67.2%, respectively. The CSS was significantly different in patients with positive and negative deep ILNM (median 1.7 years vs not reached, p<0.01). Patients who presented with deep ILNM had worse CSS (median 3.8 years vs not reached, p<0.01) in those with negative PLNs.ConclusionsDeep ILNM is the most accurate factor for predicting PLNM in PSCC according to our data. We recommend that patients with deep ILNM should be referred for pelvic lymph node dissection. Involvement of deep ILNs indicates poor prognosis. We propose that patients with metastases of deep ILNs may be staged as pN3.

| S-EPMC8479104 | biostudies-literature

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