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Cancers
Special Issues
Translational and Comparative Research on Innovative Anti-Cancer Therapies
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Translational and Comparative Research on Innovative Anti-Cancer Therapies

A special issue of Cancers (ISSN 2072-6694). This special issue belongs to the section "Cancer Therapy".

Deadline for manuscript submissions: closed (15 March 2022) | Viewed by 42639

Printed Edition Available!
A printed edition of this Special Issue is available here.

Special Issue Editors

Dr. Felisbina Luisa Queiroga

E-Mail Website
Guest Editor
Animal and Veterinary Research Centre (CECAV), Department of Veterinary Sciences, University of Trás-Os-Montes and Alto Douro, Vila Real, Portugal
Interests: small animals internal medicine; small animals oncology; small animals clinical pathology; small animals immunohistochemistry; small animals nefro-urology; small animals endocrinology
Special Issues, Collections and Topics in MDPI journals
Dr. Bruno Cogliati

E-Mail Website
Guest Editor
Department of Pathology, School of Veterinary Medicine and Animal Science, University of São Paulo (USP), 05508-060 São Paulo, Brazil
Interests: experimental pathology; animal models; liver disease; veterinary oncology; hepatocellular carcinoma; anti-cancer therapies; biomarkers; comparative hepatology

Special Issue Information

Dear Colleagues,

Cancer represents a major global challenge for medical practice in humans and companion animals. A plethora of basic and pre-clinical studies, involving cell cultures and animal models, have been screening novel anti-cancer drugs and innovative treatments such as immunotherapy and gene-based therapy. In addition, emerging alternative translational models based on comparative oncology have been showing promising results in anti-cancer drug discovery since companion animals develop spontaneous tumors and share the same environment as humans. Nonetheless, some gaps still exist in pre-clinical and clinical comparative animal models, in terms of biological behavior, genetics, molecular pathways, as well as the immunological features of cancer that should be fulfilled to enhance their translational value.

This Special Issue welcomes both original papers, review articles and systematic reviews addressing in vitro and in vivo models on basic cancer research as well as pre-clinical and clinical studies focusing on the development of innovative anti-cancer therapies, including those in the scope of comparative oncology.

Dr. Felisbina Queiroga
Dr. Bruno Cogliati
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. Cancers is an international peer-reviewed open access semimonthly 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 2900 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

  • anti-cancer therapies
  • animal models
  • in vitro assays
  • clinical trials
  • clinical oncology
  • comparative oncology
  • translational medicine

Published Papers (12 papers)

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Editorial

Jump to: Research, Review

3 pages, 188 KiB  
Editorial
Translational and Comparative Research on Innovative Anti-Cancer Therapies
by Felisbina Queiroga and Bruno Cogliati
Cancers 2023, 15(4), 1335; https://doi.org/10.3390/cancers15041335 - 20 Feb 2023
Cited by 2 | Viewed by 1144
Abstract
Oncology research has received considerable attention in recent years due to the increasing prevalence of cancer in human and animal populations worldwide [...] Full article
(This article belongs to the Special Issue Translational and Comparative Research on Innovative Anti-Cancer Therapies)

Research

Jump to: Editorial, Review

17 pages, 2757 KiB  
Article
Folic Acid Treatment Directly Influences the Genetic and Epigenetic Regulation along with the Associated Cellular Maintenance Processes of HT-29 and SW480 Colorectal Cancer Cell Lines
by Sára Zsigrai, Alexandra Kalmár, Barbara K. Barták, Zsófia B. Nagy, Krisztina A. Szigeti, Gábor Valcz, William Kothalawala, Titanilla Dankó, Anna Sebestyén, Gábor Barna, Orsolya Pipek, István Csabai, Zsolt Tulassay, Péter Igaz, István Takács and Béla Molnár
Cancers 2022, 14(7), 1820; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14071820 - 03 Apr 2022
Cited by 5 | Viewed by 3313
Abstract
Folic acid (FA) is a synthetic form of vitamin B9, generally used as a nutritional supplement and an adjunctive medication in cancer therapy. FA is involved in genetic and epigenetic regulation; therefore, it has a dual modulatory role in established neoplasms. We aimed [...] Read more.
Folic acid (FA) is a synthetic form of vitamin B9, generally used as a nutritional supplement and an adjunctive medication in cancer therapy. FA is involved in genetic and epigenetic regulation; therefore, it has a dual modulatory role in established neoplasms. We aimed to investigate the effect of short-term (72 h) FA supplementation on colorectal cancer; hence, HT-29 and SW480 cells were exposed to different FA concentrations (0, 100, 10,000 ng/mL). HT-29 cell proliferation and viability levels elevated after 100 ng/mL but decreased for 10,000 ng/mL FA. Additionally, a significant (p ≤ 0.05) improvement of genomic stability was detected in HT-29 cells with micronucleus scoring and comet assay. Conversely, the FA treatment did not alter these parameters in SW480 samples. RRBS results highlighted that DNA methylation changes were bidirectional in both cells, mainly affecting carcinogenesis-related pathways. Based on the microarray analysis, promoter methylation status was in accordance with FA-induced expression alterations of 27 genes. Our study demonstrates that the FA effect was highly dependent on the cell type, which can be attributed to the distinct molecular background and the different expression of proliferation- and DNA-repair-associated genes (YWHAZ, HES1, STAT3, CCL2). Moreover, new aspects of FA-regulated DNA methylation and consecutive gene expression were revealed. Full article
(This article belongs to the Special Issue Translational and Comparative Research on Innovative Anti-Cancer Therapies)
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18 pages, 4920 KiB  
Article
Effective Penetration of a Liposomal Formulation of Bleomycin through Ex-Vivo Skin Explants from Two Different Species
by Giulia Ferrari, Lisa Y. Pang, Fabio De Moliner, Marc Vendrell, Richard J. M. Reardon, Andrew J. Higgins, Sunil Chopra and David J. Argyle
Cancers 2022, 14(4), 1083; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14041083 - 21 Feb 2022
Cited by 2 | Viewed by 1961
Abstract
Bleomycin is a chemotherapy agent that, when administered systemically, can cause severe pulmonary toxicity. Bleosome is a novel formulation of bleomycin encapsulated in ultra-deformable (UD) liposomes that may be applicable as a topical chemotherapy for diseases such as non-melanoma skin cancer. To date, [...] Read more.
Bleomycin is a chemotherapy agent that, when administered systemically, can cause severe pulmonary toxicity. Bleosome is a novel formulation of bleomycin encapsulated in ultra-deformable (UD) liposomes that may be applicable as a topical chemotherapy for diseases such as non-melanoma skin cancer. To date, the ability of Bleosome to effectively penetrate through the skin has not been evaluated. In this study, we investigated the ability of Bleosome to penetrate through ex vivo skin explants from dogs and horses. We visualized the penetration of UD liposomes through the skin by transmission electron microscopy. However, to effectively image the drug itself we fluorescently labeled bleomycin prior to encapsulation within liposomes and utilized multiphoton microscopy. We showed that UD liposomes do not penetrate beyond the stratum corneum, whereas bleomycin is released from UD liposomes and can penetrate to the deeper layers of the epidermis. This is the first study to show that Bleosome can effectively penetrate through the skin. We speculate that UD liposomes are penetration enhancers in that UD liposomes carry bleomycin through the outer skin to the stratum corneum and then release the drug, allowing diffusion into the deeper layers. Our results are comparative in dogs and horses and warrant further studies on the efficacy of Bleosome as topical treatment. Full article
(This article belongs to the Special Issue Translational and Comparative Research on Innovative Anti-Cancer Therapies)
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17 pages, 2534 KiB  
Article
Proteomic Analysis Identifies FNDC1, A1BG, and Antigen Processing Proteins Associated with Tumor Heterogeneity and Malignancy in a Canine Model of Breast Cancer
by Yonara G. Cordeiro, Leandra M. Mulder, René J. M. van Zeijl, Lindsay B. Paskoski, Peter van Veelen, Arnoud de Ru, Ricardo F. Strefezzi, Bram Heijs and Heidge Fukumasu
Cancers 2021, 13(23), 5901; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13235901 - 24 Nov 2021
Cited by 10 | Viewed by 2762
Abstract
New insights into the underlying biological processes of breast cancer are needed for the development of improved markers and treatments. The complex nature of mammary cancer in dogs makes it a great model to study cancer biology since they present a high degree [...] Read more.
New insights into the underlying biological processes of breast cancer are needed for the development of improved markers and treatments. The complex nature of mammary cancer in dogs makes it a great model to study cancer biology since they present a high degree of tumor heterogeneity. In search of disease-state biomarkers candidates, we applied proteomic mass spectrometry imaging in order to simultaneously detect histopathological and molecular alterations whilst preserving morphological integrity, comparing peptide expression between intratumor populations in distinct levels of differentiation. Peptides assigned to FNDC1, A1BG, and double-matching keratins 18 and 19 presented a higher intensity in poorly differentiated regions. In contrast, we observed a lower intensity of peptides matching calnexin, PDIA3, and HSPA5 in poorly differentiated cells, which enriched for protein folding in the endoplasmic reticulum and antigen processing, assembly, and loading of class I MHC. Over-representation of collagen metabolism, coagulation cascade, extracellular matrix components, cadherin-binding and cell adhesion pathways also distinguished cell populations. Finally, an independent validation showed FNDC1, A1BG, PDIA3, HSPA5, and calnexin as significant prognostic markers for human breast cancer patients. Thus, through a spatially correlated characterization of spontaneous carcinomas, we described key proteins which can be further validated as potential prognostic biomarkers. Full article
(This article belongs to the Special Issue Translational and Comparative Research on Innovative Anti-Cancer Therapies)
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22 pages, 4111 KiB  
Article
Liquid Biopsy as a Diagnostic and Prognostic Tool for Women and Female Dogs with Breast Cancer
by Jucimara Colombo, Marina Gobbe Moschetta-Pinheiro, Adriana Alonso Novais, Bruna Ribeiro Stoppe, Enrico Dumbra Bonini, Francine Moraes Gonçalves, Heidge Fukumasu, Luiz Lehmann Coutinho, Luiz Gustavo de Almeida Chuffa and Debora Aparecida Pires de Campos Zuccari
Cancers 2021, 13(20), 5233; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13205233 - 19 Oct 2021
Cited by 8 | Viewed by 3141
Abstract
Introduction: Breast cancer (BC) is the malignant neoplasm with the highest mortality rate in women and female dogs are good models to study BC. Objective: We investigated the efficacy of liquid biopsy to detect gene mutations in the diagnosis and follow-up of women [...] Read more.
Introduction: Breast cancer (BC) is the malignant neoplasm with the highest mortality rate in women and female dogs are good models to study BC. Objective: We investigated the efficacy of liquid biopsy to detect gene mutations in the diagnosis and follow-up of women and female dogs with BC. Materials and Methods: In this study, 57 and 37 BC samples were collected from women and female dogs, respectively. After core biopsy and plasma samples were collected, the DNA and ctDNA of the tumor fragments and plasma were processed for next generation sequencing (NGS) assay. After preprocessing of the data, they were submitted to the Genome Analysis ToolKit (GATK). Results: In women, 1788 variants were identified in tumor fragments and 221 variants in plasma; 66 variants were simultaneously detected in tumors and plasma. Conversely, in female dogs, 1430 variants were found in plasma and 695 variants in tumor fragments; 59 variants were simultaneously identified in tumors and plasma. The most frequently mutated genes in the tumor fragments of women were USH2A, ATM, and IGF2R; in female dogs, they were USH2A, BRCA2, and RRM2. Plasma of women showed the most frequent genetic variations in the MAP3K1, BRCA1, and GRB7 genes, whereas plasma from female dogs had variations in the NF1, ERBB2, and KRT17 genes. Mutations in the AKT1, PIK3CA, and BRIP genes were associated with tumor recurrence, with a highly pathogenic variant in PIK3CA being particularly prominent. We also detected a gain-of-function mutation in the GRB7, MAP3K1, and MLH1 genes. Conclusion: Liquid biopsy is useful to identify specific genetic variations at the beginning of BC manifestation and may be accompanied over the entire follow-up period, thereby supporting the clinicians in refining interventions. Full article
(This article belongs to the Special Issue Translational and Comparative Research on Innovative Anti-Cancer Therapies)
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18 pages, 2822 KiB  
Article
Kallikrein 5 Inhibition by the Lympho-Epithelial Kazal-Type Related Inhibitor Hinders Matriptase-Dependent Carcinogenesis
by Elaine Zayas Marcelino da Silva, Thais Fernanda de Campos Fraga-Silva, Yao Yuan, Márcia Gaião Alves, Gabriel Azevedo Publio, Carol Kobori da Fonseca, Márcio Hideki Kodama, Gabriel Viliod Vieira, Marina Ferreira Candido, Lara Maria Alencar Ramos Innocentini, Mateus Gonçalves Miranda, Alfredo Ribeiro da Silva, Jose Carlos Alves-Filho, Vania Luiza Deperon Bonato, Ramiro Iglesias-Bartolome and Katiuchia Uzzun Sales
Cancers 2021, 13(17), 4395; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13174395 - 31 Aug 2021
Cited by 3 | Viewed by 2420
Abstract
Head and neck squamous cell carcinoma remains challenging to treat with no improvement in survival rates over the past 50 years. Thus, there is an urgent need to discover more reliable therapeutic targets and biomarkers for HNSCC. Matriptase, a type-II transmembrane serine protease, [...] Read more.
Head and neck squamous cell carcinoma remains challenging to treat with no improvement in survival rates over the past 50 years. Thus, there is an urgent need to discover more reliable therapeutic targets and biomarkers for HNSCC. Matriptase, a type-II transmembrane serine protease, induces malignant transformation in epithelial stem cells through proteolytic activation of pro-HGF and PAR-2, triggering PI3K-AKT-mTOR and NFKB signaling. The serine protease inhibitor lympho-epithelial Kazal-type-related inhibitor (LEKTI) inhibits the matriptase-driven proteolytic pathway, directly blocking kallikreins in epithelial differentiation. Hence, we hypothesized LEKTI could inhibit matriptase-dependent squamous cell carcinogenesis, thus implicating kallikreins in this process. Double-transgenic mice with simultaneous expression of matriptase and LEKTI under the keratin-5 promoter showed a prominent rescue of K5-Matriptase+/0 premalignant phenotype. Notably, in DMBA-induced SCC, heterotopic co-expression of LEKTI and matriptase delayed matriptase-driven tumor incidence and progression. Co-expression of LEKTI reverted altered Kallikrein-5 expression observed in the skin of K5-Matriptase+/0 mice, indicating that matriptase-dependent proteolytic pathway inhibition by LEKTI occurs through kallikreins. Moreover, we showed that Kallikrein-5 is necessary for PAR-2-mediated IL-8 release, YAP1-TAZ/TEAD activation, and matriptase-mediated oral squamous cell carcinoma migration. Collectively, our data identify a third signaling pathway for matriptase-dependent carcinogenesis in vivo. These findings are critical for the identification of more reliable biomarkers and effective therapeutic targets in Head and Neck cancer. Full article
(This article belongs to the Special Issue Translational and Comparative Research on Innovative Anti-Cancer Therapies)
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20 pages, 9426 KiB  
Article
Piperlongumine, a Potent Anticancer Phytotherapeutic, Induces Cell Cycle Arrest and Apoptosis In Vitro and In Vivo through the ROS/Akt Pathway in Human Thyroid Cancer Cells
by Fang-Ping Kung, Yun-Ping Lim, Wen-Ying Chao, Yi-Sheng Zhang, Hui-I Yu, Tsai-Sung Tai, Chieh-Hsiang Lu, Shu-Hsin Chen, Yi-Zhen Li, Pei-Wen Zhao, Yu-Pei Yen and Ying-Ray Lee
Cancers 2021, 13(17), 4266; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13174266 - 24 Aug 2021
Cited by 16 | Viewed by 3805
Abstract
Thyroid cancer (TC) is the most common endocrine malignancy, and its global incidence has steadily increased over the past 15 years. TC is broadly divided into well-differentiated, poorly differentiated, and undifferentiated types, depending on the histological and clinical parameters. Thus far, there are [...] Read more.
Thyroid cancer (TC) is the most common endocrine malignancy, and its global incidence has steadily increased over the past 15 years. TC is broadly divided into well-differentiated, poorly differentiated, and undifferentiated types, depending on the histological and clinical parameters. Thus far, there are no effective treatments for undifferentiated thyroid cancers or advanced and recurrent cancer. Therefore, the development of an effective therapeutic is urgently needed for such patients. Piperlongumine (PL) is a naturally occurring small molecule derived from long pepper; it is selectively toxic to cancer cells by generating reactive oxygen species (ROS). In this study, we demonstrate the potential anticancer activity of PL in four TC cell lines. For this purpose, we cultured TC cell lines and analyzed the following parameters: Cell viability, colony formation, cell cycle, apoptosis, and cellular ROS induction. PL modulated the cell cycle, induced apoptosis, and suppressed tumorigenesis in TC cell lines in a dose- and time-dependent manner through ROS induction. Meanwhile, an intrinsic caspase-dependent apoptosis pathway was observed in the TC cells under PL treatment. The activation of Erk and the suppression of the Akt/mTOR pathways through ROS induction were seen in cells treated with PL. PL-mediated apoptosis in TC cells was through the ROS-Akt pathway. Finally, the anticancer effect and safety of PL were also demonstrated in vivo. Our findings indicate that PL exhibits antitumor activity and has the potential for use as a chemotherapeutic agent against TC. This is the first study to show the sensitivity of TC cell lines to PL. Full article
(This article belongs to the Special Issue Translational and Comparative Research on Innovative Anti-Cancer Therapies)
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17 pages, 4978 KiB  
Article
miRNAs as Biomarkers for Diagnosing and Predicting Survival of Head and Neck Squamous Cell Carcinoma Patients
by Igor Piotrowski, Xiang Zhu, Tatiana Dandolini Saccon, Sarah Ashiqueali, Augusto Schneider, Allancer Divino de Carvalho Nunes, Sarah Noureddine, Agnieszka Sobecka, Wojciech Barczak, Mateusz Szewczyk, Wojciech Golusiński, Michal M. Masternak and Paweł Golusiński
Cancers 2021, 13(16), 3980; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13163980 - 06 Aug 2021
Cited by 17 | Viewed by 2704
Abstract
Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common cancer worldwide. These tumors originate from epithelial cells of the upper aerodigestive tract. HNSCC tumors in different regions can have significantly different molecular characteristics. While many microRNAs (miRNAs) have been found [...] Read more.
Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common cancer worldwide. These tumors originate from epithelial cells of the upper aerodigestive tract. HNSCC tumors in different regions can have significantly different molecular characteristics. While many microRNAs (miRNAs) have been found to be involved in the regulation of the carcinogenesis and pathogenesis of HNSCC, new HNSCC related miRNAs are still being discovered. The aim of this study was to explore potential miRNA biomarkers that can be used to diagnose HNSCC and prognose survival of HNSCC patients. For this purpose, we chose a panel of 12 miRNAs: miR-146a-5p, miR-449a, miR-126-5p, miR-34a-5p, miR-34b-5p, miR-34c-5p, miR-217-5p, miR-378c, miR-6510-3p, miR-96-5p, miR-149-5p, and miR-133a-5p. Expression of these miRNAs was measured in tumor tissue and neighboring healthy tissue collected from patients diagnosed with HNSCC (n = 79) in either the oral cavity, oropharynx, or larynx. We observed a pattern of differentially expressed miRNAs at each of these cancer locations. Our study showed that some of these miRNAs, separately or in combination, could serve as biomarkers distinguishing between healthy and tumor tissue, and their expression correlated with patients’ overall survival. Full article
(This article belongs to the Special Issue Translational and Comparative Research on Innovative Anti-Cancer Therapies)
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11 pages, 974 KiB  
Article
Intratumoral (Poly-ICLC) Therapy for Dogs with Advanced Cancers: First Report on Clinical Effectiveness, Quality of Life, and Adverse Events
by Alessandra Rinah Nogueira Voges, Rodrigo Ubukata, Karina Velloso Braga Yazbek, Otávia Luisa Caballero, Andres Mario Salazar, Cristina de Oliveira Massoco and Maria Lucia Zaidan Dagli
Cancers 2021, 13(9), 2237; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13092237 - 07 May 2021
Cited by 1 | Viewed by 2505
Abstract
Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (poly-ICLC) is a synthetic double-stranded viral RNA analog widely tested as a component of human therapeutic cancer vaccines and as a standalone agent for treating human cancers. However, there are no reports on the use of poly-ICLC for treating canine [...] Read more.
Polyinosinic-polycytidylic acid-poly-l-lysine carboxymethylcellulose (poly-ICLC) is a synthetic double-stranded viral RNA analog widely tested as a component of human therapeutic cancer vaccines and as a standalone agent for treating human cancers. However, there are no reports on the use of poly-ICLC for treating canine cancers. This study aimed to investigate the clinical efficacy, quality of life (QL), and adverse events of poly-ICLC treatment in dogs with advanced cancers. The treatment protocol consisted of weekly intratumoral doses of poly-ICLC. The canine patients underwent clinical, laboratory, and imaging tests, and their owners answered weekly QL questionnaires. Fourteen canine patients with different types of spontaneous advanced tumors were enrolled. Most dogs had received prior conventional therapies. Five dogs received at least 12 doses of poly-ICLC: the injected tumor was stable in three dogs, there was a partial response in one, and the injected tumor significantly enlarged in the other. The QL scoring remained stable or increased in most cases. Mild adverse events related to poly-ICLC were observed in 10 of the 14 patients. The data showed that intratumoral poly-ICLC therapy was well tolerated in dogs with advanced cancers, with clinical benefit and improved QL scores observed in some dogs. Full article
(This article belongs to the Special Issue Translational and Comparative Research on Innovative Anti-Cancer Therapies)
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Review

Jump to: Editorial, Research

20 pages, 1385 KiB  
Review
The Nervous System as a Regulator of Cancer Hallmarks: Insights into Therapeutic Implications
by Karla V. Torres-Juárez, Felisbina Luisa Queiroga and Laura P. Romero-Romero
Cancers 2022, 14(18), 4372; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers14184372 - 08 Sep 2022
Cited by 1 | Viewed by 1987
Abstract
The involvement of the nervous system in the development of cancer is controversial. Several authors have shown opinions and conflicting evidence that support the early effect of the nervous system on the carcinogenic process. For about a century, research has not been enough, [...] Read more.
The involvement of the nervous system in the development of cancer is controversial. Several authors have shown opinions and conflicting evidence that support the early effect of the nervous system on the carcinogenic process. For about a century, research has not been enough, questions remain open, ideas are not discarded, and although more research is still needed to answer all the questions, there is now enough evidence to support the theories and give hope of finding one more possible form of treatment. It is clear that malignant neoplasms have endogenous characteristics that allow them to establish and progress. Some of these characteristics known as hallmarks of cancer, are damage mechanisms in the pathology but necessary during other physiological processes which show some nerve dependence. The nervous system communicates with the whole organism, regulating physiological processes necessary to respond to external stimuli and for the maintenance of homeostasis. The modification of nerve activity could generate an overload and deregulate the state of cellular and tissue homeostasis; this could drive cancer development. In this review, we will address the issue in an evidence-oriented manner that supports that the nervous system is able to participate in the initial and progressive process of carcinogenesis by inducing biochemical, physiological, and cellular modifications involved in the hallmarks of cancer. Full article
(This article belongs to the Special Issue Translational and Comparative Research on Innovative Anti-Cancer Therapies)
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57 pages, 4650 KiB  
Review
In Vivo and In Vitro Models of Hepatocellular Carcinoma: Current Strategies for Translational Modeling
by Guilherme Ribeiro Romualdo, Kaat Leroy, Cícero Júlio Silva Costa, Gabriel Bacil Prata, Bart Vanderborght, Tereza Cristina da Silva, Luís Fernando Barbisan, Wellington Andraus, Lindsey Devisscher, Niels Olsen Saraiva Câmara, Mathieu Vinken and Bruno Cogliati
Cancers 2021, 13(21), 5583; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13215583 - 08 Nov 2021
Cited by 17 | Viewed by 6262
Abstract
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer-related death globally. HCC is a complex multistep disease and usually emerges in the setting of chronic liver diseases. The molecular pathogenesis of HCC varies according to [...] Read more.
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide and the third leading cause of cancer-related death globally. HCC is a complex multistep disease and usually emerges in the setting of chronic liver diseases. The molecular pathogenesis of HCC varies according to the etiology, mainly caused by chronic hepatitis B and C virus infections, chronic alcohol consumption, aflatoxin-contaminated food, and non-alcoholic fatty liver disease associated with metabolic syndrome or diabetes mellitus. The establishment of HCC models has become essential for both basic and translational research to improve our understanding of the pathophysiology and unravel new molecular drivers of this disease. The ideal model should recapitulate key events observed during hepatocarcinogenesis and HCC progression in view of establishing effective diagnostic and therapeutic strategies to be translated into clinical practice. Despite considerable efforts currently devoted to liver cancer research, only a few anti-HCC drugs are available, and patient prognosis and survival are still poor. The present paper provides a state-of-the-art overview of in vivo and in vitro models used for translational modeling of HCC with a specific focus on their key molecular hallmarks. Full article
(This article belongs to the Special Issue Translational and Comparative Research on Innovative Anti-Cancer Therapies)
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23 pages, 2448 KiB  
Review
Valproic Acid and Breast Cancer: State of the Art in 2021
by Anna Wawruszak, Marta Halasa, Estera Okon, Wirginia Kukula-Koch and Andrzej Stepulak
Cancers 2021, 13(14), 3409; https://0-doi-org.brum.beds.ac.uk/10.3390/cancers13143409 - 07 Jul 2021
Cited by 32 | Viewed by 8979
Abstract
Valproic acid (2-propylpentanoic acid, VPA) is a short-chain fatty acid, a member of the group of histone deacetylase inhibitors (HDIs). VPA has been successfully used in the treatment of epilepsy, bipolar disorders, and schizophrenia for over 50 years. Numerous in vitro and in [...] Read more.
Valproic acid (2-propylpentanoic acid, VPA) is a short-chain fatty acid, a member of the group of histone deacetylase inhibitors (HDIs). VPA has been successfully used in the treatment of epilepsy, bipolar disorders, and schizophrenia for over 50 years. Numerous in vitro and in vivo pre-clinical studies suggest that this well-known anticonvulsant drug significantly inhibits cancer cell proliferation by modulating multiple signaling pathways. Breast cancer (BC) is the most common malignancy affecting women worldwide. Despite significant progress in the treatment of BC, serious adverse effects, high toxicity to normal cells, and the occurrence of multi-drug resistance (MDR) still limit the effective therapy of BC patients. Thus, new agents which improve the effectiveness of currently used methods, decrease the emergence of MDR, and increase disease-free survival are highly needed. This review focuses on in vitro and in vivo experimental data on VPA, applied individually or in combination with other anti-cancer agents, in the treatment of different histological subtypes of BC. Full article
(This article belongs to the Special Issue Translational and Comparative Research on Innovative Anti-Cancer Therapies)
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