Melanoma targeting with the loco-regional chemotherapeutic, Melphalan: From cell death to immunotherapeutic efficacy

Dudek-Perić, Aleksandra M.; Gołąb, Jakub; Garg, Abhishek D.; Agostinis, Patrizia

doi:10.1080/2162402x.2015.1054600

Cited by 4 publications

(4 citation statements)

References 10 publications

(11 reference statements)

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“…SJW extracts are also the main source of natural hypericin. This naphtodianthrone is regarded as an efficient anticancer compound that induces an apoptotic response after specifically binding to melanoma cancer cells [ 28 ]. The successful application of hypericin in cancer photodynamic therapy (PDT) takes advantage of the properties of hypericin as one of the most powerful photosensitizers known in nature [ 11 ].…”

Section: The Relevance Of Hyperforin Hypericin and Other Bioactivmentioning

confidence: 99%

The Biochemical and Genetic Basis for the Biosynthesis of Bioactive Compounds in Hypericum perforatum L., One of the Largest Medicinal Crops in Europe

Rizzo

Altschmied

Ravindran

et al. 2020

Genes

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Hypericum perforatum L. commonly known as Saint John’s Wort (SJW), is an important medicinal plant that has been used for more than 2000 years. Although H. perforatum produces several bioactive compounds, its importance is mainly linked to two molecules highly relevant for the pharmaceutical industry: the prenylated phloroglucinol hyperforin and the naphtodianthrone hypericin. The first functions as a natural antidepressant while the second is regarded as a powerful anticancer drug and as a useful compound for the treatment of Alzheimer’s disease. While the antidepressant activity of SJW extracts motivate a multi-billion dollar industry around the world, the scientific interest centers around the biosynthetic pathways of hyperforin and hypericin and their medical applications. Here, we focus on what is known about these processes and evaluate the possibilities of combining state of the art omics, genome editing, and synthetic biology to unlock applications that would be of great value for the pharmaceutical and medical industries.

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Section: The Relevance Of Hyperforin Hypericin and Other Bioactivmentioning

confidence: 99%

The Biochemical and Genetic Basis for the Biosynthesis of Bioactive Compounds in Hypericum perforatum L., One of the Largest Medicinal Crops in Europe

Rizzo

Altschmied

Ravindran

et al. 2020

Genes

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“…Whereas hyperforin is contained in translucent (or pale) glands (Ciccarelli et al, 2001;Soelberg et al, 2007) which give the leaf a perforated appearance and hence the species its scientific name, hypericin on the other hand accumulates in so-called dark glands (DGs) which differentiate in leaves (Zobayed et al, 2006) and other tissues ( Figure S1). Hypericin is considered a promising agent for cancer photodynamic therapy (Dudek-Peri c et al, 2015;Garg et al, 2010Garg et al, , 2012 being classified as a type II immunogenic cell death (ICD) inducer (Krysko et al, 2013). By targeting the endoplasmic reticulum, hypericin induces cellular damage and apoptosis signalling (Krysko et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Discovery of key regulators of dark gland development and hypericin biosynthesis in St. John's Wort (Hypericum perforatum)

Rizzo

Altschmied

Stark

et al. 2019

Plant Biotechnology Journal

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Summary Hypericin is a molecule of high pharmaceutical importance that is synthesized and stored in dark glands (DGs) of St. John's Wort (Hypericum perforatum). Understanding which genes are involved in dark gland development and hypericin biosynthesis is important for the development of new Hypericum extracts that are highly demanded for medical applications. We identified two transcription factors whose expression is strictly synchronized with the differentiation of DGs. We correlated the content of hypericin, pseudohypericin, endocrocin, skyrin glycosides and several flavonoids with gene expression and DG development to obtain a revised model for hypericin biosynthesis. Here, we report for the first time genotypes which are polymorphic for the presence/total absence (G+/G−) of DGs in their placental tissues (PTs). DG development was characterized in PTs using several microscopy techniques. Fourier transform infrared microscopy was established as a novel method to precisely locate polyaromatic compounds, such as hypericin, in plant tissues. In addition, we obtained transcriptome and metabolome profiles of unprecedented resolution in Hypericum. This study addresses for the first time the development of dark glands and identifies genes that constitute strong building blocks for the further elucidation of hypericin synthesis, its manipulation in plants, its engineering in microbial systems and its applications in medical research.

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“…Finally, selecting the appropriate agents for intraperitoneal chemotherapy is a major consideration, especially in recurrent disease. Sarcomas for the most part are considered chemoresistant and melphalan has been described as a successful agent in the treatment of aggressive chemoresistant neoplasms, such as soft tissue sarcomas and melanomas of the extremities when combined with hyperthermia . Alkylating agents such as melphalan, cyclophosphamide, and ifosfamide had the highest activation energy by hyperthermia , with melphalan having the greatest thermal enhancement cytotoxicity and drug penetration into tumor .…”

Section: Discussionmentioning

confidence: 99%

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in seven patients with peritoneal sarcomatosis from uterine sarcoma

Sardi

Muñoz‐Zuluaga

Sittig

et al. 2018

Clinical Case Reports

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Key Clinical MessagePeritoneal sarcomatosis from uterine sarcoma is a rare disease with no effective treatment and poor prognosis. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) has successful results in peritoneal carcinomatosis from gastrointestinal/gynecological origins. We show that CRS/HIPEC is safe, feasible, and may benefit selected patients with peritoneal sarcomatosis from uterine sarcoma.

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Melanoma targeting with the loco-regional chemotherapeutic, Melphalan: From cell death to immunotherapeutic efficacy

Cited by 4 publications

References 10 publications

The Biochemical and Genetic Basis for the Biosynthesis of Bioactive Compounds in Hypericum perforatum L., One of the Largest Medicinal Crops in Europe

The Biochemical and Genetic Basis for the Biosynthesis of Bioactive Compounds in Hypericum perforatum L., One of the Largest Medicinal Crops in Europe

Discovery of key regulators of dark gland development and hypericin biosynthesis in St. John's Wort (Hypericum perforatum)

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in seven patients with peritoneal sarcomatosis from uterine sarcoma

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