Outcomes and clinical characteristics of the compassionate use of plitidepsin in COVID-19 patients with solid tumours, haematological malignancies or anti-CD20 antibody treatment.

Objective: To study the effect of plitidepsin antiviral treatment in immunocompromised COVID-19 patients with underlying haematological malignancies or solid tumours, particularly those who have undergone anti-CD20 therapies.

Design: We conducted a retrospective observational study, involving 54 adults treated with plitidepsin on compassionate use as an antiviral drug. Our analysis compared outcomes between patients with solid tumours and those with haematological malignancies, and a cohort of cases treated or not with anti-CD20 monoclonal antibodies.

SARS-CoV-2 variants evolve convergent strategies to remodel the host response.

SARS-CoV-2 variants of concern (VOCs) emerged during the COVID-19 pandemic. Here, we used unbiased systems approaches to study the host-selective forces driving VOC evolution. We discovered that VOCs evolved convergent strategies to remodel the host by modulating viral RNA and protein levels, altering viral and host protein phosphorylation, and rewiring virus-host protein-protein interactions.

Outcomes and clinical characteristics of the compassionate use of plitidepsin for immunocompromised adult patients with COVID-19.

Objectives: To evaluate the compassionate use of plitidepsin as an antiviral treatment in hospitalized immunocompromised adult patients with moderate-to-severe COVID-19.

Design: Retrospective observational study of data -collected from January 01, 2021 to April 30, 2022- from 35 immunocompromised adult patients with COVID-19 non-eligible for other available antiviral treatments. Main outcome measures were time to respiratory recovery (SpFi ≥ 315); COVID-19-related 30-day-cumulative mortality after first plitidepsin infusion; and time to undetectable levels of viral RNA.

Plitidepsin in adult patients with COVID-19 requiring hospital admission: A long-term follow-up analysis.

Introduction: The APLICOV-PC study assessed the safety and preliminary efficacy of plitidepsin in hospitalized adult patients with COVID-19. In this follow-up study (E-APLICOV), the incidence of post-COVID-19 morbidity was evaluated and any long-term complications were characterized.

Methods: Between January 18 and March 16, 2022, 34 of the 45 adult patients who received therapy with plitidepsin in the APLICOV-PC study were enrolled in E-APLICOV (median time from plitidepsin first dose to E-APLICOV enrollment, 16.

Plitidepsin has a positive therapeutic index in adult patients with COVID-19 requiring hospitalization.

Unlabelled: Plitidepsin is a marine-derived cyclic-peptide that inhibits SARS-CoV-2 replication at low nanomolar concentrations by the targeting of host protein eEF1A (eukaryotic translation-elongation-factor-1A). We evaluated a model of intervention with plitidepsin in hospitalized COVID-19 adult patients where three doses were assessed (1.5, 2 and 2.

Plitidepsin (Aplidin) is a potent inhibitor of diffuse large cell and Burkitt lymphoma and is synergistic with rituximab.

Plitidepsin (Aplidin), an antitumor agent of marine origin, presently is undergoing phase II/III clinical trials, and has shown promise for the treatment of lymphoma. Here, we describe the antitumor effects of plitidepsin alone and in combination with rituximab and investigated the effects of each drug and the combination on the cell cycle and mechanism of cell death. Several Diffuse Large Cell Lymphoma (DLCL) lines and Burkitt cell lines were tested for sensitivity to plitidepsin and rituximab.

Diverse cross-resistance phenotype to ET-743 and PM00104 in multi-drug resistant cell lines.

Purpose: ET-743 (Yondelis, trabectedin) and PM00104 (Zalypsis) are marine derived compounds which demonstrate anti-tumor activity. The present study was performed to elucidate the relationship between the expression of ABCB1/MDR1 and ABCC1/MRP1 with resistance to either ET-743 or PM00104.

Methods: We evaluate the association between expression of Pgp1, MRP1, and BCRP proteins and ET-743 or PM00104 resistance in a large panel of multi-drug resistant cell lines derived from histologically unrelated human tumors that were selected with paclitaxel, doxorubicin, cisplatin, mitoxantrane, or gemcitibine.

In vitro radiosensitisation by trabectedin in human cancer cell lines.

Purpose: To examine the potential radiosensitising properties of trabectedin (ET-743, Yondelis).

Methods And Materials: In vitro chemosensitivity was assessed in four tumour cell lines (DU145, HeLa, HT29, HOP62) by the crystal violet method. IC10s and IC50s were established for 1-h, 24-h and 7-day (continuous) exposure times.

Phase I clinical and pharmacokinetic study of kahalalide F in patients with advanced androgen refractory prostate cancer.

Purpose: The purpose is to determine the maximum tolerated dose, profile of adverse events, and dose-limiting toxicity of Kahalalide F (KF) in patients with androgen refractory prostate cancer. Furthermore, the pharmacokinetics after KF administration and preliminary antitumor activity were evaluated. KF is a dehydroaminobutyric acid-containing peptide isolated from the marine herbivorous mollusk, Elysia rufescens.

Liquid chromatographic assay for the cyclic depsipeptide aplidine, a new marine antitumor drug, in whole blood using derivatization with trans-4'-hydrazino-2-stilbazole.

A sensitive bio-analytical assay for the depsipeptide aplidine in plasma has been modified and tested for human whole blood samples. The adapted method is based on reversed-phase liquid chromatography and fluorescence detection of the trans-4'-hydrazino-2-stilbazole derivative of the analyte. Aplidine is isolated from the matrix by solid-phase extraction on an octadecyl modified silica stationary phase.

A clinical armamentarium of marine-derived anti-cancer compounds.

The sea, covering 70% of the Earth's surface, offers a considerably broader spectrum of biological diversity than terra firma. Containing approximately 75% of all living organisms, the marine environment offers a rich source of natural products with potential therapeutic application. Marine organisms have evolved the enzymatic capability to produce potent chemical entities that make them promising sources of innovative cytotoxic compounds.