Dr. Jill Kruse describes the signs of different types of skin cancers.

PDR 2023-01-11 Dr. Jill Kruse - Skin Cancer

A new research paper was published in Oncotarget’s Volume 13 on December 29, 2022, entitled, “Calcium signaling induced by 15-deoxy-prostamide-J2 promotes cell death by activating PERK, IP3R, and the mitochondrial permeability transition pore.”

Melanoma is the deadliest form of skin cancer in the US. Although immunotherapeutic checkpoint inhibitors and small-molecule kinase inhibitors have dramatically increased the survival of patients with melanoma, new or optimized therapeutic approaches are still needed to improve outcomes. 15-deoxy-Δ12,14-prostamide J2 (15d-PMJ2) is an investigational small-molecule that induces ER stress-mediated apoptosis selectively in tumor cells. Additionally, 15d-PMJ2 reduces melanoma growth in vivo. 

To assess the chemotherapeutic potential of 15d-PMJ2, researchers Daniel A. Ladin, Margaret M. Nelson, Estefani Cota, Catherine Colonna, Colin Burns, Jacques Robidoux, Kelsey H. Fisher-Wellman, and Rukiyah Van Dross-Anderson from East Carolina University and University of North Carolina at Chapel Hill sought to uncover molecular pathways by which 15d-PMJ2 exerts its antitumor activity. 

B16F10 melanoma and JWF2 squamous cell carcinoma cell lines were cultured in the presence of pharmacological agents that prevent ER or oxidative stress as well as Ca2+ channel blockers to identify mechanisms of 15d-PMJ2 cell death. 

“Our data demonstrated the ER stress protein, PERK, was required for 15d-PMJ2-induced death.”

PERK activation triggered the release of ER-resident Ca2+ through an IP3R sensitive pathway. Increased calcium mobilization led to mitochondrial Ca2+ overload followed by mitochondrial permeability transition pore (mPTP) opening and the deterioration of mitochondrial respiration. Finally, the researchers showed that the electrophilic double bond located within the cyclopentenone ring of 15d-PMJ2 was required for its activity. 

“The present study identifies PERK/IP3R/mPTP signaling as a mechanism of 15d-PMJ2 antitumor activity.”

DOI: https://doi.org/10.18632/oncotarget.28334 

Correspondence to: Rukiyah Van Dross-Anderson - vandrossr@ecu.edu 

Keywords: calcium, mitochondrial respiration, endoplasmic reticulum stress, cancer, prostamide

About Oncotarget: 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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Oncotarget

Calcium Signaling Induced by 15-deoxy-prostamide-J2 Promotes Cell Death by...

#askdrmudgil #skincancer #thedrmudgilpodcast 

Using this great question from #reddit to shed some light on skin cancer. 

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Episode 65 - Skin Cancer 101

Us Together

Gaurav Gupta, venture capitalist with Lightspeed Venture Partners; and Dr. Roxana Daneshjou, a Stanford dermatologist studying artificial intelligence and machine learning in skin-cancer detection, on the promise -vs- hazards -vs- hype in the exploding field of AI.

Welcome to the Machine

A new research paper was published in Oncotarget's Volume 14 on May 26, 2023, entitled, “Deconstructing the role of MALAT1 in MAPK-signaling in melanoma: insights from antisense oligonucleotide treatment.”

The long non-coding RNA (lncRNA) MALAT1 is a regulator of oncogenesis and cancer progression. MAPK-pathway upregulation is the main event in the development and progression of human cancer, including melanoma and recent studies have shown that MALAT1 has a significant impact on the regulation of gene and protein expression in the MAPK pathway. However, the role of MALAT1 in regulation of gene and protein expression of the MAPK-pathway kinases RAS, RAF, MEK, and ERK in melanoma is largely unknown. 

In this study, researchers Valentin Feichtenschlager, Yixuan James Zheng, Wilson Ho, Linan Chen, Ciara Callanan, Christopher Chen, Albert Lee, Jose Ortiz, Klemens Rappersberger, and Susana Ortiz-Urda from the University of California San Francisco and Medical University Vienna demonstrated the impacts of antisense oligonucleotide (ASO)-based MALAT1-inhibition on MAPK-pathway gene regulation in melanoma.
 
“Our results showed that MALAT1-ASO treatment decreased BRAF RNA expression and protein levels, and MALAT1 had increased correlation with MAPK-pathway associated genes in melanoma patient samples compared to healthy skin.”

Additionally, drug-induced MAPK inhibition upregulated MALAT1-expression, a finding that resonates with a paradigm of MALAT1-expression presented in this work: MALAT1 is downregulated in melanoma and other cancer types in which MALAT1 seems to be associated with MAPK-signaling, while MALAT1-ASO treatment strongly reduced the growth of melanoma cell lines, even in cases of resistance to MEK inhibition. MALAT1-ASO treatment significantly inhibited colony formation in vitro and reduced tumor growth in an NRAS-mutant melanoma xenograft mouse model in vivo, while showing no aberrant toxic side effects. 

“Our findings demonstrate new insights into MALAT1-mediated MAPK-pathway gene regulation and a paradigm of MALAT1 expression in MAPK-signaling-dependent cancer types. MALAT1 maintains essential oncogenic functions, despite being downregulated.”

DOI - https://doi.org/10.18632/oncotarget.28447

Correspondence to - Valentin Feichtenschlager - valentin.feichtenschlager@ucsf.edu

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Keywords - MALAT1, MAPK-pathway, BRAF, melanoma, antisense oligonucleotides

About Oncotarget

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form, and then quickly released to Pubmed. On September 15, 2022, Oncotarget was accepted again for indexing by MEDLINE. Oncotarget is now indexed by Medline/PubMed and PMC/PubMed.

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Deconstructing the Role of MALAT1 in MAPK-Signaling in Melanoma

Dr. Andrew Ellsworth answers questions about plantar fasciitis, mental health, skin cancer, and congestive heart failure.

PDR 2023-06-07 Dr. Andrew Ellsworth - Ask Anything

The Youth Matter's Women's Hour with Cadence Verhoef airs every Wednesday on 98.5 One FM Radio Shepparton and discusses the topics that matter to women in our community and nation wide.

Today (Wednesday the 28th of June, 2023) Cadence talks about the issue of skin cancer.

Women's Hour with Cadence Verhoef airs on OneFM 98.5 from 6pm to 7pm on Wednesday nights.  

Contact the station on admin@fm985.com.au or (+613) 58313131 https://fm985.com.au/

The ONE FM 98.5 Community Radio podcast page operates under the APRA AMCOS and ACMA  license of Goulburn Valley Community Radio Inc. (One FM)Number 1385226/1.). This program is made with thanks to the Community Broadcasting Foundation.

Youth Matters - Women's Hour Cadence talks about skin cancer

A new research paper was published in Oncotarget's Volume 14 on July 7, 2023, entitled, “Effectiveness and toxicity of cetuximab with concurrent RT in locally advanced cutaneous squamous cell skin cancer: a case series.”

Treatment for locally advanced cutaneous squamous cell cancers (laCSCC) remains poorly defined. Most laCSCC tumors express high levels of epidermal growth factor receptors (EGFR). Cetuximab has activity in other EGFR expressing cancers and enhances the effectiveness of radiotherapy.

In this new study, researchers Mark Chang, Wolfram Samlowski and Raul Meoz from University Medical Center of Southern Nevada, Comprehensive Cancer Centers of Nevada, University of Nevada Las Vegas, and University of Nevada Reno conducted a retrospective review of institutional data and identified 18 patients with laCSCC treated with cetuximab induction and concurrent radiotherapy. 

“We performed a retrospectively review of treatment outcome and toxicity in our patients who received concurrent cetuximab and radiotherapy to show an additional potentially effective treatment option for patients with laCSCC. The goal is also to provide data to inform the design of potential prospective clinical trials.”

The loading dose of cetuximab was 400 mg/m² IV. Subsequent weekly doses of 250 mg/m² IV were infused throughout the period of radiation. The treatment doses ranged from 4500–7000 cGy, with a dose fraction of 200-250 cGy. The objective response rate was 83.2% with 55.5% complete responses and 27.7% partial responses. 

Median progression-free survival was 21.6 months. Progression-free survival was 61% at 1 year and 40% at 2 years. With longer follow-up, some patients developed a local recurrence (16.7%), distant metastases (11.1%) or a second primary cancer (16.3%). Cetuximab was well tolerated, with 68.4% patients experienced only mild acneiform skin rash or fatigue (Grade 1 or 2). Radiotherapy produced expected side effects (skin erythema, moist desquamation, mucositis).

“Cetuximab plus radiotherapy represents an active and tolerable treatment option for laCSCC, including patients with contraindications for checkpoint inhibitor therapy.”

DOI - https://doi.org/10.18632/oncotarget.28470

Correspondence to - Wolfram Samlowski - wsamlowski1@gmail.com

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Keywords - keratinocyte carcinoma, squamous cell skin cancer, cetuximab, epidermal growth factor receptor, radiation therapy

About Oncotarget: 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

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Cetuximab's Effectiveness and Toxicity in Advanced Cutaneous Squamous Cell Skin Cancer

The Youth Matter's Women's Hour with Cadence Verhoef airs every Wednesday on 98.5 One FM Radio Shepparton and discusses the topics that matter to women in our community and nation wide.

Today (Wednesday the 5th of July, 2023) Cadence talks about the issue of skin cancer.

Women's Hour with Cadence Verhoef airs on OneFM 98.5 from 6pm to 7pm on Wednesday nights.  

Contact the station on admin@fm985.com.au or (+613) 58313131 https://fm985.com.au/

The ONE FM 98.5 Community Radio podcast page operates under the APRA AMCOS and ACMA  license of Goulburn Valley Community Radio Inc. (One FM)Number 1385226/1.). This program is made with thanks to the Community Broadcasting Foundation.

Youth Matters - Women's Hour Cadence talks a bit more about skin cancer

BUFFALO, NY- July 26, 2024 – A new #research paper was #published in Oncotarget's Volume 15 on July 19, 2024, entitled, “Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma.”

Macrophage Migration Inhibitory Factor (MIF) and its homolog D-dopachrome Tautomerase (DDT) have been implicated as drivers of tumor progression across a variety of cancers. Recent evidence suggests MIF as a therapeutic target in immune checkpoint inhibition (ICI) resistant melanomas, however clinical evidence of MIF and particularly of DDT remain limited.

In this new retrospective study, researchers Caroline Naomi Valdez, Gabriela Athziri Sánchez-Zuno, Lais Osmani, Wael Ibrahim, Anjela Galan, Antonietta Bacchiocchi, Ruth Halaban, Rajan P. Kulkarni, Insoo Kang, Richard Bucala, and Thuy Tran from Yale University, Oregon Health and Science University, Cancer Early Detection Advanced Research Center (CEDAR), and the Department of Veterans Affairs Portland Health Care System analyzed 97 patients treated at Yale for melanoma between 2002–2020. 

“Our study significantly expands on prior work by De Azevedo et al. by encompassing a larger cohort of individuals, coupled with a comprehensive approach to defining high and low MIF and DDT expression.”

Bulk-RNA sequencing of patient tumor samples from the Skin Cancer SPORE Biorepository was used to evaluate for differential gene expression of MIF, DDT, CD74, and selected inflammatory markers, and gene expression was correlated with patient survival outcomes. Their findings revealed a strong correlation between MIF and DDT levels, with no statistically significant difference across common melanoma mutations and subtypes. 

Improved survival was associated with lower MIF and DDT levels and higher CD74:MIF and CD74:DDT levels. High CD74:DDT and CD74:MIF levels were also associated with enrichment of infiltrating inflammatory cell markers. These data suggest DDT as a novel target in immune therapy. Dual MIF and DDT blockade may provide synergistic responses in patients with melanoma, irrespective of common mutations, and may overcome ICI resistance. These markers may also provide prognostic value for further biomarker development.

“Our study is the first to report survival findings in association with intratumor DDT expression and CD74:DDT expression level ratio. Thus, CD74:MIF and CD74:DDT expression ratio measurements offer promise as prognostic markers for survival outcomes and ICI response in patients with melanoma.”

DOI - https://doi.org/10.18632/oncotarget.28615

Correspondence to - Thuy Tran - thuy.tran@yale.edu

Video short - https://www.youtube.com/watch?v=ULlzscn0PvQ

Subscribe for free publication alerts from Oncotarget - https://www.oncotarget.com/subscribe/

Keywords - cancer, MIF, DDT, melanoma, immune checkpoint inhibition, cancer transcriptomics

About Oncotarget 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

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Prognostic and Therapeutic Insights Into MIF, DDT, and CD74 in Melanoma

Macrophage Migration Inhibitory Factor (MIF) and its homolog D-dopachrome Tautomerase (DDT) have been implicated as drivers of tumor progression in various cancers. Recent evidence suggests that MIF could be a therapeutic target in immune checkpoint inhibition (ICI) resistant melanomas; however, clinical evidence for MIF, and particularly for DDT, remains limited.

Researchers Caroline Naomi Valdez, Gabriela Athziri Sánchez-Zuno, Lais Osmani, Wael Ibrahim, Anjela Galan, Antonietta Bacchiocchi, Ruth Halaban, Rajan P. Kulkarni, Insoo Kang, Richard Bucala, and Thuy Tran from Yale University; Oregon Health and Science University; Cancer Early Detection Advanced Research Center (CEDAR); and the Department of Veterans Affairs Portland Health Care System analyzed 97 patients treated at Yale for melanoma between 2002–2020. Their research paper was published in Oncotarget’s Volume 15 on July 19, 2024, entitled, “Prognostic and therapeutic insights into MIF, DDT, and CD74 in melanoma.”

Full blog - https://www.oncotarget.org/2024/08/28/key-roles-of-mif-ddt-and-cd74-in-melanoma-prognosis-and-therapy/

Paper DOI - https://doi.org/10.18632/oncotarget.28615

Correspondence to - Thuy Tran - thuy.tran@yale.edu

Video short - https://www.youtube.com/watch?v=ULlzscn0PvQ

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Keywords - cancer, MIF, DDT, melanoma, immune checkpoint inhibition, cancer transcriptomics

About Oncotarget 

Oncotarget (a primarily oncology-focused, peer-reviewed, open access journal) aims to maximize research impact through insightful peer-review; eliminate borders between specialties by linking different fields of oncology, cancer research and biomedical sciences; and foster application of basic and clinical science.

Oncotarget is indexed and archived by PubMed/Medline, PubMed Central, Scopus, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).

To learn more about Oncotarget, please visit https://www.oncotarget.com and connect with us:

Facebook - https://www.facebook.com/Oncotarget/
X - https://twitter.com/oncotarget
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MEDIA@IMPACTJOURNALS.COM

Key Roles of MIF, DDT, and CD74 in Melanoma Prognosis and Therapy

Oncotarget is a primarily oncology-focused, peer-reviewed, open access journal. Papers are published continuously within yearly volumes in their final and complete form and then quickly released to Pubmed.

Oncotarget is now indexed by MEDLINE, PubMed and PMC/PubMed.

Read about the Oncotarget Scientific Integrity Process: https://www.oncotarget.com/scientific_integrity/

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