Special Issue "Research on Cancer Biology"

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Oncology".

Deadline for manuscript submissions: closed (31 July 2021).

Special Issue Editor

Dr. Alberto Ouro Villasante
E-Mail Website1 Website2
Guest Editor
Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, The National Institute for Biotechnology in the Negev, Beer-Sheva 8410501, Israel
Interests: sphingolipids; cancer; inflammation; signaling pathways; neurosciences; Alzheimer’s disease; memory
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

To understand the mechanisms that lead to cancer development and progression, researchers must first understand the differences between normal and cancer cells, and, therefore, the importance of elucidating the processes that involve such differences. In recent decades, great advances have been made in cancer treatments that could not have been carried out without the knowledge acquired in the study of cancer biology. One of the most important points in these advances has been the diversification of the study areas, such as metabolism, proteogenomics, sphingolipids, signaling pathways, immune system or tumor microenvironments. Technological and experimental advances in cancer biology are essential for the development of clinical therapies. Collaborations between different disciplines notoriously increase the opportunity to understand the mechanisms that give rise to the appearance of cancer cells and their advances in different stages. This Special Issue provides the opportunity to share and contribute to the knowledge of cancer biology from different disciplines.

Dr. Alberto Ouro Villasante
Guest Editor

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 papers will be 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. Medicina 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 1500 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

  • Cancer
  • Tumor
  • Metastasis
  • Metabolism
  • Microenviroment
  • Signaling pathway
  • Proteogenomic
  • Immune system
  • Somatic stem cell

Published Papers (7 papers)

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Editorial

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Editorial
Cancer Biology Analysis—Tackled from Different Points of View
Medicina 2021, 57(9), 937; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57090937 - 05 Sep 2021
Viewed by 405
Abstract
In the last few decades, great advances have been made in the detection and treatment of cancer, thus increasing the survival rate [...] Full article
(This article belongs to the Special Issue Research on Cancer Biology)

Research

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Article
Role of Luteolin-Induced Apoptosis and Autophagy in Human Glioblastoma Cell Lines
Medicina 2021, 57(9), 879; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57090879 - 26 Aug 2021
Cited by 1 | Viewed by 538
Abstract
Background and Objectives: Malignant glioblastoma (GBM) is caused by abnormal proliferation of glial cells, which are found in the brain. The therapeutic effects of surgical treatment, radiation therapy, and chemo-therapy against GBM are relatively poor compared with their effects against other tumors. Luteolin [...] Read more.
Background and Objectives: Malignant glioblastoma (GBM) is caused by abnormal proliferation of glial cells, which are found in the brain. The therapeutic effects of surgical treatment, radiation therapy, and chemo-therapy against GBM are relatively poor compared with their effects against other tumors. Luteolin is abundant in peanut shells and is also found in herbs and other plants, such as thyme, green pepper, and celery. Luteolin is known to be effective against obesity and metabolic syndrome. The anti-inflammatory, and anti-cancer activities of luteolin have been investigated. Most studies have focused on the antioxidant and anti-inflammatory effects of luteolin, which is a natural flavonoid. However, the association between the induction of apoptosis by luteolin in GBM and autophagy has not yet been investigated. This study thus aimed to confirm the occurrence of luteolin-induced apoptosis and autophagy in GBM cells and to assess their relationship. Materials and Methods: A172 and U-373MG glioblastoma cell lines were used for this experiment. We confirmed the apoptosis effect of Luteolin on GBM cells using methods such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, immunofluorescence, Flow cytometry (FACS) western blot, and real-time quantitative PCR (qPCR). Results: In the luteolin-treated A172 and U-373MG cells, cell viability decreased in a concentration- and time-dependent manner. In addition, in A172 and U-373MG cells treated with luteolin at concentrations greater than 100 μM, nuclear fragmentation, which is a typical morphological change characterizing apoptosis, as well as fragmentation of caspase-3 and Poly (ADP-ribose) polymerase (PARP), which are apoptosis-related factors, were observed. Autophagy was induced after treatment with at least 50 μM luteolin. Inhibition of autophagy using 3MA allowed for a low concentration of luteolin to more effectively induce apoptosis in A172 and U-373MG cells. Conclusions: Results showed that luteolin induces apoptosis and autophagy and that the luteolin-induced autophagy promotes cell survival. Therefore, an appropriate combination therapy involving luteolin and an autophagy inhibitor is expected to improve the prognosis of GBM treatment. Full article
(This article belongs to the Special Issue Research on Cancer Biology)
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Article
Role of the Inflammatory Response of RAW 264.7 Cells in the Metastasis of Novel Cancer Stem-Like Cells
Medicina 2021, 57(8), 778; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57080778 - 30 Jul 2021
Cited by 1 | Viewed by 593
Abstract
Background and objectives: Tumor progression and the immune response are intricately linked. Additionally, the presence of macrophages in the microenvironment is essential for carcinogenesis, but regulation of the polarization of M1- and M2-like macrophages and their role in metastasis remain unclear. Based [...] Read more.
Background and objectives: Tumor progression and the immune response are intricately linked. Additionally, the presence of macrophages in the microenvironment is essential for carcinogenesis, but regulation of the polarization of M1- and M2-like macrophages and their role in metastasis remain unclear. Based on previous studies, both reactive oxygen species (ROS) and the endoplasmic reticulum (ER) are emerging as key players in macrophage polarization. While it is known that cancers alter macrophage inflammatory responses to promote tumor progression, there is limited knowledge regarding how they affect the macrophage-dependent innate host defense. Materials and methods: We detected the levels of ROS, the ability of chemotaxis, the expressions of markers of M1-/M2-like macrophages in RAW264.7 in presence of T2- and T2C-conditioned medium. Results: The results of this study indicated that ROS levels were decreased in RAW 264.7 cells when cultured with T2C-conditioned medium, while there was an improvement in chemotaxis abilities. We also found that the M2-like macrophages were characterized by an elongated shape in RAW 264.7 cells cultured in T2C-conditioned medium, which had increased CD206 expression but decreased expression of CD86 and inducible nitric oxide synthase. Suppression of ER stress shifted polarized M1-like macrophages toward an M2-like phenotype in RAW 264.7 cells cultured in T2C-conditioned medium. Conclusions: Taken together, we conclude that the polarization of macrophages is associated with the alteration of cell shape, ROS accumulation, and ER stress. Full article
(This article belongs to the Special Issue Research on Cancer Biology)
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Article
From Benign Inflammatory Dermatosis to Cutaneous Lymphoma. DNA Copy Number Imbalances in Mycosis Fungoides versus Large Plaque Parapsoriasis
Medicina 2021, 57(5), 502; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57050502 - 15 May 2021
Cited by 1 | Viewed by 743
Abstract
Background and Objectives: Mycosis fungoides (MF) and large plaque parapsoriasis (LPP) evolution provide intriguing data and are the cause of numerous debates. The diagnosis of MF and LPP is associated with confusion and imprecise definition. Copy number alterations (CNAs) may play an essential [...] Read more.
Background and Objectives: Mycosis fungoides (MF) and large plaque parapsoriasis (LPP) evolution provide intriguing data and are the cause of numerous debates. The diagnosis of MF and LPP is associated with confusion and imprecise definition. Copy number alterations (CNAs) may play an essential role in the genesis of cancer out of genes expression dysregulation. Objectives: Due to the heterogeneity of MF and LPP and the scarcity of the cases, there are an exceedingly small number of studies that have identified molecular changes in these pathologies. We aim to identify and compare DNA copy number alterations and gene expression changes between MF and LPP to highlight the similarities and the differences between these pathologies. Materials and Methods: The patients were prospectively selected from University Clinic of Dermatology and Venereology Timișoara, Romania. From fresh frozen skin biopsies, we extracted DNA using single nucleotide polymorphism (SNP) data. The use of SNP array for copy number profiling is a promising approach for genome-wide analysis. Results: After reviewing each group, we observed that the histograms generated for chromosome 1–22 were remarkably similar and had a lot of CNAs in common, but also significant differences were seen. Conclusions: This study took a step forward in finding out the differences and similarities between MF and LPP, for a more specific and implicitly correct approach of the case. The similarity between these two pathologies in terms of CNAs is striking, emphasizing once again the difficulty of approaching and differentiating them. Full article
(This article belongs to the Special Issue Research on Cancer Biology)
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Article
Rare Occurrence of Microsatellite Instability in Gastrointestinal Stromal Tumors
Medicina 2021, 57(2), 174; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57020174 - 18 Feb 2021
Cited by 1 | Viewed by 665
Abstract
Background and Objectives: This study aimed to objectively determine microsatellite instability (MSI) status using a next-generation sequencing (NGS)-based MSI panel and to resolve the discrepancy regarding whether or not MSI is a rare phenomenon, irrespective of diverse genomic alterations in gastrointestinal stromal tumors [...] Read more.
Background and Objectives: This study aimed to objectively determine microsatellite instability (MSI) status using a next-generation sequencing (NGS)-based MSI panel and to resolve the discrepancy regarding whether or not MSI is a rare phenomenon, irrespective of diverse genomic alterations in gastrointestinal stromal tumors (GISTs). Materials and Methods: Genomic DNA was subjected to MSI panel sequencing using an Ion AmpliSeq Microsatellite Instability Assay, as well as to cancer gene panel sequencing using an Oncomine Focus DNA Assay. Results: All of our GIST patients showed microsatellite-stable (MSS) status, which confirmed that MSI status did not affect the molecular pathogenesis of GIST. The KIT gene (79%, 38/48) was the most frequently mutated gene, followed by the PDGFRA (8%, 4/48), PIK3CA (8%, 4/48), and ERBB2 (4%, 2/48) mutations. KIT exon 11 mutant patients were more favorable in responding to imatinib than those with exon 9 mutant or wild-type GISTs, and compared to non-KIT exon 11 mutant GISTs (p = 0.041). The NGS-based MSI panel with MSICall confirmed a rare phenomenon of microsatellite instability in GISTs irrespective of diverse genomic alterations. Conclusion: Massively parallel sequencing can simultaneously provide the MSI status as well as the somatic mutation profile in a single test. This combined approach may help us to understand the molecular pathogenesis of GIST carcinogenesis and malignant progression. Full article
(This article belongs to the Special Issue Research on Cancer Biology)
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Review

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Review
Ceramide Metabolism Enzymes—Therapeutic Targets against Cancer
Medicina 2021, 57(7), 729; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57070729 - 19 Jul 2021
Cited by 1 | Viewed by 1416
Abstract
Sphingolipids are both structural molecules that are essential for cell architecture and second messengers that are involved in numerous cell functions. Ceramide is the central hub of sphingolipid metabolism. In addition to being the precursor of complex sphingolipids, ceramides induce cell cycle arrest [...] Read more.
Sphingolipids are both structural molecules that are essential for cell architecture and second messengers that are involved in numerous cell functions. Ceramide is the central hub of sphingolipid metabolism. In addition to being the precursor of complex sphingolipids, ceramides induce cell cycle arrest and promote cell death and inflammation. At least some of the enzymes involved in the regulation of sphingolipid metabolism are altered in carcinogenesis, and some are targets for anticancer drugs. A number of scientific reports have shown how alterations in sphingolipid pools can affect cell proliferation, survival and migration. Determination of sphingolipid levels and the regulation of the enzymes that are implicated in their metabolism is a key factor for developing novel therapeutic strategies or improving conventional therapies. The present review highlights the importance of bioactive sphingolipids and their regulatory enzymes as targets for therapeutic interventions with especial emphasis in carcinogenesis and cancer dissemination. Full article
(This article belongs to the Special Issue Research on Cancer Biology)
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Review
Spontaneous and Induced Tumors in Germ-Free Animals: A General Review
Medicina 2021, 57(3), 260; https://0-doi-org.brum.beds.ac.uk/10.3390/medicina57030260 - 11 Mar 2021
Cited by 1 | Viewed by 556
Abstract
Cancer, bacteria, and immunity relationships are much-debated topics in the last decade. Microbiome’s importance for metabolic and immunologic modulation of the organism adaptation and responses has become progressively evident, and models to study these relationships, especially about carcinogenesis, have acquired primary importance. The [...] Read more.
Cancer, bacteria, and immunity relationships are much-debated topics in the last decade. Microbiome’s importance for metabolic and immunologic modulation of the organism adaptation and responses has become progressively evident, and models to study these relationships, especially about carcinogenesis, have acquired primary importance. The availability of germ-free (GF) animals, i.e., animals born and maintained under completely sterile conditions avoiding the microbiome development offers a unique tool to investigate the role that bacteria can have in carcinogenesis and tumor development. The comparison between GF animals with the conventional (CV) counterpart with microbiome can help to evidence conditions and mechanisms directly involving bacterial activities in the modulation of carcinogenesis processes. Here, we review the literature about spontaneous cancer and cancer modeling in GF animals since the early studies, trying to offer a practical overview on the argument. Full article
(This article belongs to the Special Issue Research on Cancer Biology)
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