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Biomedicines
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Advances in Cancer Biology and Experimental Anticancer Therapies
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Advances in Cancer Biology and Experimental Anticancer Therapies

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (30 April 2024) | Viewed by 9587

Special Issue Editors

Dr. Damian Gawel

E-Mail Website
Guest Editor
1. Centre of Postgraduate Medical Education, Department of Immunohematology, Marymoncka 99/103, 01-813 Warsaw, Poland
2. Centre of Postgraduate Medical Education, Department of Biochemistry and Molecular Biology, Marymoncka 99/103, 01-813 Warsaw, Poland
Interests: cancer cell biology; biomarkers; cancer cell survival mechanisms; micro-RNAs; multidrug resistance; nanotools; experimental anticancer therapies
Dr. Tiziana Vavalà

E-Mail Website
Guest Editor
AOU Città della Salute e della Scienza, Torino, Italy
Interests: clinical oncology; metastasis; lung cancer; cell biology; Cancer Research; tumors; chemotherapy; cancer biology; cancer biomarkers

Special Issue Information

Dear Colleagues,

Cancer rates are on the rise. Among the various barriers to tumor treatment, the phenomenon of multidrug resistance (MDR) is a major obstacle limiting the effectiveness of the administered chemo drugs. Therefore, it is essential to intensify studies on the molecular mechanisms of carcinogenesis and develop novel tactics to predict, diagnose, and fight tumors. Currently, selective kinase inhibitors, micro-RNAs, nano-based theranostic tools, and combinatory approaches are considered the most promising strategies. This issue aims to provide an update on the currently investigated molecular factors promoting the progression of cancer and antitumor therapeutic strategies.

Dr. Damian Gawel
Dr. Tiziana Vavalà
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomedicines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • signaling pathways
  • metastasis
  • multidrug resistance
  • experimental anticancer therapies
  • exosomes
  • nano-tools
  • targeted therapies

Published Papers (6 papers)

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Research

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15 pages, 3816 KiB  
Article
Rotundifuran Induces Ferroptotic Cell Death and Mitochondria Permeability Transition in Lung Cancer Cells
by Myung-Ji Kang, Dong-Oh Moon, Ji-Yoon Park, Namho Kim, Su Hyeon Lee, Hyung Won Ryu, Yang Hoon Huh, Hyun-Sun Lee and Mun-Ock Kim
Biomedicines 2024, 12(3), 576; https://doi.org/10.3390/biomedicines12030576 - 05 Mar 2024
Viewed by 782
Abstract
Rotundifuran (RF), a potent anti-inflammatory and anti-cancer compound, is a natural compound predominantly present in Vitex Rotundifolia. Herein, we investigated the effects of RF on the growth of lung cancer cells. Our findings suggested that RF inhibits cell growth, highlighting its potential [...] Read more.
Rotundifuran (RF), a potent anti-inflammatory and anti-cancer compound, is a natural compound predominantly present in Vitex Rotundifolia. Herein, we investigated the effects of RF on the growth of lung cancer cells. Our findings suggested that RF inhibits cell growth, highlighting its potential as a therapeutic agent for cancer treatment. Interestingly, we observed that cell growth inhibition was not due to apoptosis, as caspases were not activated and DNA fragmentation did not occur. Furthermore, we found that intracellular vacuoles and autophagy were induced, but RF-induced cell death was not affected when autophagy was inhibited. This prompted us to investigate other possible mechanisms underlying cell growth inhibition. Through a cDNA chip analysis, we confirmed changes in the expression of ferroptosis-related genes and observed lipid peroxidation. We further examined the effect of ferroptosis inhibitors and found that they alleviated cell growth inhibition induced by RF. We also observed the involvement of calcium signaling, ROS accumulation, and JNK signaling in the induction of ferroptosis. Our findings suggested that RF is a potent anti-cancer drug and further studies are needed to validate its clinal use. Full article
(This article belongs to the Special Issue Advances in Cancer Biology and Experimental Anticancer Therapies)
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16 pages, 3209 KiB  
Article
A Novel Druggable Dual-Specificity tYrosine-Regulated Kinase3/Calmodulin Kinase-like Vesicle-Associated Signaling Module with Therapeutic Implications in Neuroblastoma
by Esteban J. Rozen, Kim Wigglesworth and Jason M. Shohet
Biomedicines 2024, 12(1), 197; https://doi.org/10.3390/biomedicines12010197 - 16 Jan 2024
Viewed by 942
Abstract
High-risk neuroblastoma is a very aggressive pediatric cancer, accounting for ~15% of childhood cancer mortality. Therefore, novel therapeutic strategies for the treatment of neuroblastoma are urgently sought. Here, we focused on the potential implications of the Dual-specificity tYrosine-Regulated Kinase (DYRK) family and downstream [...] Read more.
High-risk neuroblastoma is a very aggressive pediatric cancer, accounting for ~15% of childhood cancer mortality. Therefore, novel therapeutic strategies for the treatment of neuroblastoma are urgently sought. Here, we focused on the potential implications of the Dual-specificity tYrosine-Regulated Kinase (DYRK) family and downstream signaling pathways. We used bioinformatic analysis of public datasets from neuroblastoma cohorts and cell lines to search correlations between patient survival and expression of DYRK kinases. Additionally, we performed biochemical, molecular, and cellular approaches to validate and characterize our observations, as well as an in vivo orthotopic murine model of neuroblastoma. We identified the DYRK3 kinase as a critical mediator of neuroblastoma cell proliferation and in vivo tumor growth. DYRK3 has recently emerged as a key regulator of several biomolecular condensates and has been linked to the hypoxic response of neuroblastoma cells. Our data suggest a role for DYRK3 as a regulator of the neuroblastoma-specific protein CAMKV, which is also required for neuroblastoma cell proliferation. CAMKV is a very understudied member of the Ca2+/calmodulin-dependent protein kinase family, originally described as a pseudokinase. We show that CAMKV is phosphorylated by DYRK3, and that inhibition of DYRK3 kinase activity induces CAMKV aggregation, probably mediated by its highly disordered C-terminal half. Importantly, we provide evidence that the DYRK3/CAMKV signaling module could play an important role for the function of the mitotic spindle during cell division. Our data strongly support the idea that inhibition of DYRK3 and/or CAMKV in neuroblastoma cells could constitute an innovative and highly specific intervention to fight against this dreadful cancer. Full article
(This article belongs to the Special Issue Advances in Cancer Biology and Experimental Anticancer Therapies)
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29 pages, 9768 KiB  
Article
2-Aminoethyl Dihydrogen Phosphate (2-AEH2P) Associated with Cell Metabolism-Modulating Drugs Presents a Synergistic and Pro-Apoptotic Effect in an In Vitro Model of the Ascitic Ehrlich Tumor
by Monique G. Alves, Laertty G. S. Cabral, Paulo G. F. Totti, Felipe R. Azarias, Karine T. Pomini, Rose E. G. Rici, Rosa A. N. Laiso and Durvanei A. Maria
Biomedicines 2024, 12(1), 109; https://doi.org/10.3390/biomedicines12010109 - 04 Jan 2024
Viewed by 907
Abstract
The progression and maintenance of cancer characteristics are associated with cellular components linked to the tumor and non-cellular components with pro-tumoral properties. Pharmacological association with antagonists of the cellular components of the tumor, such as anti- and pro-apoptotic drugs, represents a novel adjuvant [...] Read more.
The progression and maintenance of cancer characteristics are associated with cellular components linked to the tumor and non-cellular components with pro-tumoral properties. Pharmacological association with antagonists of the cellular components of the tumor, such as anti- and pro-apoptotic drugs, represents a novel adjuvant strategy. In this study, the antiproliferative, pro-apoptotic, and pharmacological effects of the combination of monophosphoester 2-AEH2P with Simvastatin, Coenzyme Q10, the chemotherapeutic drug paclitaxel, and colony-stimulating factor (GM-CSF) were evaluated. Tests were conducted to determine cytotoxic activity using the MTT method, cell cycle phases, and fragmented DNA by flow cytometry, mitochondrial membrane potential, expression of cell markers Bcl2, TNF-α/DR-4, Cytochrome c, caspase 3, and P53, and analysis of drug combination profiles using Synergy Finder 2.0 Software. The results showed a synergistic effect among the combinations, compared to individual treatments with the monophosphoester and other drugs. In addition, there was modulation of marker expression, indicating a pro-apoptotic and immunomodulatory effect of 2-AEH2P. Pharmacological analysis revealed that tumor cells treated with GM-CSF + 2-AEH2P exhibited a synergistic effect, while groups of tumor cells treated with paclitaxel, Coenzyme Q10, and Simvastatin showed additive effects. Furthermore, treatment with the paclitaxel + 2-AEH2P combination (12 h) resulted in a significant reduction in mitochondrial membrane potential. Pharmacological combinations for normal cells did not exhibit deleterious effects compared to mammary carcinomatosis tumor (EAT) cells. Full article
(This article belongs to the Special Issue Advances in Cancer Biology and Experimental Anticancer Therapies)
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22 pages, 7809 KiB  
Article
Anti-Cancer Potential of Transiently Transfected HER2-Specific Human Mixed CAR-T and NK Cell Populations in Experimental Models: Initial Studies on Fucosylated Chondroitin Sulfate Usage for Safer Treatment
by Irina O. Chikileva, Alexandra V. Bruter, Nadezhda A. Persiyantseva, Maria A. Zamkova, Raimonda Ya. Vlasenko, Yuliya I. Dolzhikova, Irina Zh. Shubina, Fedor V. Donenko, Olga V. Lebedinskaya, Darina V. Sokolova, Vadim S. Pokrovsky, Polina O. Fedorova, Nadezhda E. Ustyuzhanina, Natalia Yu. Anisimova, Nikolay E. Nifantiev and Mikhail V. Kiselevskiy
Biomedicines 2023, 11(9), 2563; https://doi.org/10.3390/biomedicines11092563 - 18 Sep 2023
Cited by 1 | Viewed by 1358
Abstract
Human epidermal growth factor receptor 2 (HER2) is overexpressed in numerous cancer cell types. Therapeutic antibodies and chimeric antigen receptors (CARs) against HER2 were developed to treat human tumors. The major limitation of anti-HER2 CAR-T lymphocyte therapy is attributable to the low HER2 [...] Read more.
Human epidermal growth factor receptor 2 (HER2) is overexpressed in numerous cancer cell types. Therapeutic antibodies and chimeric antigen receptors (CARs) against HER2 were developed to treat human tumors. The major limitation of anti-HER2 CAR-T lymphocyte therapy is attributable to the low HER2 expression in a wide range of normal tissues. Thus, side effects are caused by CAR lymphocyte “on-target off-tumor” reactions. We aimed to develop safer HER2-targeting CAR-based therapy. CAR constructs against HER2 tumor-associated antigen (TAA) for transient expression were delivered into target T and natural killer (NK) cells by an effective and safe non-viral transfection method via nucleofection, excluding the risk of mutations associated with viral transduction. Different in vitro end-point and real-time assays of the CAR lymphocyte antitumor cytotoxicity and in vivo human HER2-positive tumor xenograft mice model proved potent cytotoxic activity of the generated CAR-T-NK cells. Our data suggest transient expression of anti-HER2 CARs in plasmid vectors by human lymphocytes as a safer treatment for HER2-positive human cancers. We also conducted preliminary investigations to elucidate if fucosylated chondroitin sulfate may be used as a possible agent to decrease excessive cytokine production without negative impact on the CAR lymphocyte antitumor effect. Full article
(This article belongs to the Special Issue Advances in Cancer Biology and Experimental Anticancer Therapies)
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11 pages, 2692 KiB  
Article
High-Resolution Magic-Angle-Spinning NMR in Revealing Hepatoblastoma Hallmarks
by Ljubica Tasic, Nataša Avramović, Milka Jadranin, Melissa Quintero, Danijela Stanisic, Lucas G. Martins, Tássia Brena Barroso Carneiro Costa, Estela Novak, Vicente Odone, Maria Rivas, Talita Aguiar, Dirce Maria Carraro, Isabela Werneck da Cunha, Cecilia Maria Lima da Costa, Mariana Maschietto and Ana Krepischi
Biomedicines 2022, 10(12), 3091; https://doi.org/10.3390/biomedicines10123091 - 01 Dec 2022
Cited by 3 | Viewed by 1429
Abstract
Cancer is one of the leading causes of death in children and adolescents worldwide; among the types of liver cancer, hepatoblastoma (HBL) is the most common in childhood. Although it affects only two to three individuals in a million, it is mostly asymptomatic [...] Read more.
Cancer is one of the leading causes of death in children and adolescents worldwide; among the types of liver cancer, hepatoblastoma (HBL) is the most common in childhood. Although it affects only two to three individuals in a million, it is mostly asymptomatic at diagnosis, so by the time it is detected it has already advanced. There are specific recommendations regarding HBL treatment, and ongoing studies to stratify the risks of HBL, understand the pathology, and predict prognostics and survival rates. Although magnetic resonance imaging spectroscopy is frequently used in diagnostics of HBL, high-resolution magic-angle-spinning (HR-MAS) NMR spectroscopy of HBL tissues is scarce. Using this technique, we studied the alterations among tissue metabolites of ex vivo samples from (a) HBL and non-cancer liver tissues (NCL), (b) HBL and adjacent non-tumor samples, and (c) two regions of the same HBL samples, one more centralized and the other at the edge of the tumor. It was possible to identify metabolites in HBL, then metabolites from the HBL center and the border samples, and link them to altered metabolisms in tumor tissues, highlighting their potential as biochemical markers. Metabolites closely related to liver metabolisms such as some phospholipids, triacylglycerides, fatty acids, glucose, and amino acids showed differences between the tissues. Full article
(This article belongs to the Special Issue Advances in Cancer Biology and Experimental Anticancer Therapies)
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Review

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23 pages, 1312 KiB  
Review
Ribosome-Directed Therapies in Cancer
by Gazmend Temaj, Silvia Chichiarelli, Margherita Eufemi, Fabio Altieri, Rifat Hadziselimovic, Ammad Ahmad Farooqi, Ilhan Yaylim and Luciano Saso
Biomedicines 2022, 10(9), 2088; https://doi.org/10.3390/biomedicines10092088 - 26 Aug 2022
Cited by 7 | Viewed by 3525
Abstract
The human ribosomes are the cellular machines that participate in protein synthesis, which is deeply affected during cancer transformation by different oncoproteins and is shown to provide cancer cell proliferation and therefore biomass. Cancer diseases are associated with an increase in ribosome biogenesis [...] Read more.
The human ribosomes are the cellular machines that participate in protein synthesis, which is deeply affected during cancer transformation by different oncoproteins and is shown to provide cancer cell proliferation and therefore biomass. Cancer diseases are associated with an increase in ribosome biogenesis and mutation of ribosomal proteins. The ribosome represents an attractive anti-cancer therapy target and several strategies are used to identify specific drugs. Here we review the role of different drugs that may decrease ribosome biogenesis and cancer cell proliferation. Full article
(This article belongs to the Special Issue Advances in Cancer Biology and Experimental Anticancer Therapies)
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