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In 2019, the scientific and medical community celebrated the 50th anniversary of the introduction of the very first marine-derived drug, Cytarabine, into clinics [...].In 2019, the scientific and medical community celebrated the 50th anniversary of the introduction of the very first marine-derived drug, Cytarabine, into clinics [...].

By the end of the year 2020, there are nine marine-derived anticancer drugs available on the market, and the field is currently growing exponentially [...].By the end of the year 2020, there are nine marine-derived anticancer drugs available on the market, and the field is currently growing exponentially [...].

The field of marine bioactive compounds (marine drugs) has evolved significantly in recent years [...].The field of marine bioactive compounds (marine drugs) has evolved significantly in recent years [...].

Das BuchUmfassender Überblick zu Tumorentitäten und Behandlungskonzepten.-Klassifikation, Klinik, Diagnostik-aktuelle, evidenzgesicherte Behandlungskonzepte-Empfehlungen und gängige Therapieschemata-Onkologische Notfälle, Supportivmaßnahmen und Palliativmedizin-MedikamentenübersichtVerfasst von interdisziplinären Autorenteams.Mit evidenzbasierten Handlungsempfehlungen.Für die tägliche Arbeit in Praxis und Klinik - für konzentrierten Überblick und zum Selbststudium.Online-VersionDie Online-Version des Taschenbuchs Hämatologie und Onkologie ist unter www.onkologie2024.de zugänglich.

The role of subcellular survivin compartmentalization in the biology and prognosis of prostate cancer is unclear. We therefore investigated subcellular localization of survivin in more than 3000 prostate cancer patients by quantitative immunohistochemistry and performed transcriptomics of 250 prostate cancer patients and healthy donors using publicly available datasets. Survivin (BIRC5) gene expression was increased in primary prostate cancers and metastases, but did not differ in recurrent vs non-recurrent prostate cancers. Survivin immunohistochemistry (IHC) staining was limited exclusively to the nucleus in 900 prostate cancers (40.0%), and accompanied by various levels of cytoplasmic positivity in 1338 tumors (59.4%). 0.5% of prostate cancers did not express survivin. Nuclear and cytoplasmic survivin staining intensities were strongly associated with each other, pT category, and higher Gleason scores. Cytoplasmic but not nuclear survivin staining correlated with high tumor cell proliferation in prostate cancers. Strong cytoplasmic survivin staining, but not nuclear staining predicted an unfavorable outcome in univariate analyses. Multivariate Cox regression analysis showed that survivin is not an independent prognostic marker. In conclusion, we provide evidence that survivin expression is increased in prostate cancers, especially in metastatic disease, resulting in higher aggressiveness and tumor progression. In addition, subcellular compartmentalization is an important aspect of survivin cancer biology, as only cytoplasmic, but not nuclear survivin accumulation is linked to biological aggressiveness and prognosis of prostate cancers.

By the end of 2017, there were seven marine-derived pharmaceutical substances that have been approved by the FDA for clinical use as drugs[...].By the end of 2017, there were seven marine-derived pharmaceutical substances that have been approved by the FDA for clinical use as drugs[...].

In Western countries, cancer is among the most frequent causes of death. Despite striking advances in cancer therapy, there is still an urgent need for new drugs in oncology. Current development favors so called “targeted agents” or drugs that target the immune system, i.e., therapeutic antibodies that enhance or facilitate an immune response against tumor cells (also referred to as “checkpoint inhibitors”). However, until recently, roughly 60% of drugs used in hematology and oncology were originally derived from natural sources, and one third of the top-selling agents are either natural agents or derivatives [1]. There is justified hope for the discovery and development of new anticancer agents from the marine environment. Historically, this habitat has proven to be a rich source of potent natural compounds such as alkaloids, steroids, terpenes, macrolides, peptides, and polyketides, among others. Interestingly, marine agents and cancer treatment have had a special relationship from the beginning. One of the first marine-derived compounds, discovered in 1945 that was later developed into a clinically used drug, was spongothymidine [2–4], which was the lead compound for the discovery of cytarabine [5]. Until today, cytarabine remains one of the most widely used agents in the treatment of acute myeloid leukemia and relapsed aggressive lymphomas. [...]

Background Germ cell tumors (GCTs) are developmental cancers, tightly linked to embryogenesis and germ cell development. The recent and expanding field of RNA modifications is being increasingly implicated in such molecular events, as well as in tumor progression and resistance to therapy, but still rarely explored in GCTs. In this work, and as a follow-up of our recent study on this topic in TGCT tissue samples, we aim to investigate the role of N6-methyladenosine (m 6 A), the most abundant of such modifications in mRNA, in in vitro and in vivo models representative of such tumors. Methods Four cell lines representative of GCTs (three testicular and one mediastinal), including an isogenic cisplatin resistant subline, were used. CRISPR/Cas9-mediated knockdown of VIRMA was established and the chorioallantoic membrane assay was used to study its phenotypic effect in vivo. Results We demonstrated the differential expression of the various m 6 A writers, readers and erasers in GCT cell lines representative of the major classes of these tumors, seminomas and non-seminomas, and we evidenced changes occurring upon differentiation with all-trans retinoic acid treatment. We showed differential expression also among cells sensitive and resistant to cisplatin treatment, implicating these players in acquisition of cisplatin resistant phenotype. Knockdown of VIRMA led to disruption of the remaining methyltransferase complex and decrease in m 6 A abundance, as well as overall reduced tumor aggressiveness (with decreased cell viability, tumor cell proliferation, migration, and invasion) and increased sensitivity to cisplatin treatment, both in vitro and confirmed in vivo. Enhanced response to cisplatin after VIRMA knockdown was related to significant increase in DNA damage (with higher γH2AX and GADD45B levels) and downregulation of XLF and MRE11. Conclusions VIRMA has an oncogenic role in GCTs confirming our previous tissue-based study and is further involved in response to cisplatin by interfering with DNA repair. These data contribute to our better understanding of the emergence of cisplatin resistance in GCTs and support recent attempts to therapeutically target elements of the m 6 A writer complex.

According to the PubMed database (US National Library of Medicine National Institutes of Health) the number of the annual publications referring to “autophagy” has risen over the last ten years more than 50 times from 128 papers/year (in 2009) to more than 7300 papers/year (in 2019, data for the middle of December 2019) and its total number has reached 46,000 [2]. [...]in 2016, the Nobel Prize in Physiology or Medicine was awarded to Prof. Yoshinori Ohsumi for “his discoveries of mechanisms for autophagy” [3]. [...]in conditions like cancer, excessive autophagy may be a positive factor at early stages of tumorigenesis (as it leads to the elimination of cancer cells via type II cell death), but negative at late stages of tumor development (as it might help malignant cells to overcome conditions of cellular stress and activate survival under chemo- and radiotherapy) [5,6]. [...]the biochemical tools which allow us to control and manipulate this process are of high impact and interest in biomedical science. [...]the number of annually published articles related to “autophagy” and “marine” topics has increased 25 times over the last decade (from 3/year in 2009 up to 76/year in 2019, according to the PubMed database) [14].

During mammalian development the fertilized zygote and primordial germ cells lose their DNA methylation within one cell cycle leading to the concept of active DNA demethylation. Recent studies identified the TET hydroxylases as key enzymes responsible for active DNA demethylation, catalyzing the oxidation of 5-methylcytosine to 5-hydroxymethylcytosine. Further oxidation and activation of the base excision repair mechanism leads to replacement of a modified cytosine by an unmodified one. In this study, we analyzed the expression/activity of TET1-3 and screened for the presence of 5 mC oxidation products in adult human testis and in germ cell cancers. By analyzing human testis sections, we show that levels of 5-hydroxymethylcytosine, 5-formylcytosine and 5-carboxylcytosine are decreasing as spermatogenesis proceeds, while 5-methylcytosine levels remain constant. These data indicate that during spermatogenesis active DNA demethylation becomes downregulated leading to a conservation of the methylation marks in mature sperm. We demonstrate that all carcinoma in situ and the majority of seminomas are hypomethylated and hypohydroxymethylated compared to non-seminomas. Interestingly, 5-formylcytosine and 5-carboxylcytosine were detectable in all germ cell cancer entities analyzed, but levels did not correlate to the 5-methylcytosine or 5-hydroxymethylcytosine status. A meta-analysis of gene expression data of germ cell cancer tissues and corresponding cell lines demonstrates high expression of TET1 and the DNA glycosylase TDG, suggesting that germ cell cancers utilize the oxidation pathway for active DNA demethylation. During xenograft experiments, where seminoma-like TCam-2 cells transit to an embryonal carcinoma-like state DNMT3B and DNMT3L where strongly upregulated, which correlated to increasing 5-methylcytosine levels. Additionally, 5-hydroxymethylcytosine levels were elevated, demonstrating that de novo methylation and active demethylation accompanies this transition process. Finally, mutations of IDH1 (IDH1 (R132)) and IDH2 (IDH2 (R172)) leading to production of the TET inhibiting oncometabolite 2-hydroxyglutarate in germ cell cancer cell lines were not detected.