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Cells
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Translational Research on Solid Tumors
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Translational Research on Solid Tumors

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cellular Pathology".

Deadline for manuscript submissions: closed (31 March 2023) | Viewed by 10261

Special Issue Editors

Dr. Paola Ulivi

E-Mail Website
Guest Editor
Biosciences Laboratory, Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, via P. Maroncelli 40, 47014 Meldola, Italy
Interests: translational research; biomarkers; liquid biopsy; oncology
Special Issues, Collections and Topics in MDPI journals
Dr. Milena Urbini

E-Mail Website
Guest Editor
Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” (IRST) , via P. Maroncelli 40, 47014 Meldola, Italy
Interests: molecular biology; oncology; translational research; next-generation sequencing
Special Issues, Collections and Topics in MDPI journals
Dr. Giorgia Marisi

E-Mail Website
Guest Editor
Biosciences Laboratory, IRCCS Istituto Romagnolo per lo Studio dei Tumori “Dino Amadori” (IRST), via P. Maroncelli 40, 47014 Meldola, Italy
Interests: molecular biology; oncology; translational research; liquid biopsy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues, 

In recent years, the treatment of solid tumors has focused more on the personalization of treatment, gradually orienting itself towards what is defined as precision medicine. Tumor molecular characteristics, tumor microenvironment composition, and other patient’s characteristics heavily affect prognosis and response to therapy. Moreover, for many types of cancers, the tumor molecular characterization represents the starting point for treatment decision making. Moreover, the heterogeneity of the tumor and its evolution during treatment have led to the use of alternative and non-invasive methods for molecular characterization, such as liquid biopsy.

For the current Special Issue, we invite contributions which showcase the latest research in terms of tumor and microenvironment molecular characterization, in relation to prognosis and response to therapy, also focalizing on the use of non-invasive methods for molecular characterization.

This Special Issue will include (but is not limited to) papers on the following topics: 

  • prognostic biomarkers;
  • tumor heterogeneity;
  • resistance mechanisms to therapy;
  • tumor microenvironment;
  • liquid biopsy;
  • epigenetics;
  • targeted therapy;
  • immunotherapy.

Dr. Paola Ulivi
Dr. Milena Urbini
Dr. Giorgia Marisi
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. Cells 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 2700 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

  • translational research
  • oncology
  • liquid biopsy

Related Special Issue

Published Papers (6 papers)

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Research

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12 pages, 960 KiB  
Article
Prognostic Role of Circulating Tumor Cell Trajectories in Metastatic Colorectal Cancer
by Valentina Magri, Luca Marino, Chiara Nicolazzo, Angela Gradilone, Gianluigi De Renzi, Michela De Meo, Orietta Gandini, Arianna Sabatini, Daniele Santini, Enrico Cortesi and Paola Gazzaniga
Cells 2023, 12(8), 1172; https://doi.org/10.3390/cells12081172 - 16 Apr 2023
Cited by 4 | Viewed by 1703
Abstract
Background: A large amount of evidence from clinical studies has demonstrated that circulating tumor cells are strong predictors of outcomes in many cancers. However, the clinical significance of CTC enumeration in metastatic colorectal cancer is still questioned. The aim of this study was [...] Read more.
Background: A large amount of evidence from clinical studies has demonstrated that circulating tumor cells are strong predictors of outcomes in many cancers. However, the clinical significance of CTC enumeration in metastatic colorectal cancer is still questioned. The aim of this study was to evaluate the clinical value of CTC dynamics in mCRC patients receiving first-line treatments. Materials and methods: Serial CTC data from 218 patients were used to identify CTC trajectory patterns during the course of treatment. CTCs were evaluated at baseline, at a first-time point check and at the radiological progression of the disease. CTC dynamics were correlated with clinical endpoints. Results: Using a cut-off of ≥1 CTC/7.5 mL, four prognostic trajectories were outlined. The best prognosis was obtained for patients with no evidence of CTCs at any timepoints, with a significant difference compared to all other groups. Lower PFS and OS were recognized in group 4 (CTCs always positive) at 7 and 16 months, respectively. Conclusions: We confirmed the clinical value of CTC positivity, even with only one cell detected. CTC trajectories are better prognostic indicators than CTC enumeration at baseline. The reported prognostic groups might help to improve risk stratification, providing potential biomarkers to monitor first-line treatments. Full article
(This article belongs to the Special Issue Translational Research on Solid Tumors)
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18 pages, 5601 KiB  
Article
Molecular Analysis of the Superior Efficacy of a Dual Epidermal Growth Factor Receptor (EGFR)-DNA-Targeting Combi-Molecule in Comparison with Its Putative Prodrugs 6-Mono-Alkylamino- and 6,6-Dialkylaminoquinazoline in a Human Osteosarcoma Xenograft Model
by Caterina Facchin, Ana B. Fraga-Timiraos, Julie Schmitt, Nadia Babaa, Naveet Pannu, Antonio Aliaga, Anne-Laure Larroque and Bertrand J. Jean-Claude
Cells 2023, 12(6), 914; https://doi.org/10.3390/cells12060914 - 16 Mar 2023
Viewed by 1484
Abstract
Background: ZR2002 is a dual EGFR-DNA-targeting combi-molecule that carries a chloroethyl group at the six-position of the quinazoline ring designed to alkylate DNA. Despite its good pharmacokinetics, ZR2002 is metabolized in vivo into dechlorinated metabolites, losing the DNA-alkylating function required to damage [...] Read more.
Background: ZR2002 is a dual EGFR-DNA-targeting combi-molecule that carries a chloroethyl group at the six-position of the quinazoline ring designed to alkylate DNA. Despite its good pharmacokinetics, ZR2002 is metabolized in vivo into dechlorinated metabolites, losing the DNA-alkylating function required to damage DNA. To increase the DNA damage activity in tumor cells in vivo, we compared ZR2002 with two of its 6-N,N-disubstituted analogs: “JS61”, with a nitrogen mustard function at the six-position of the quinazoline ring, and “JS84”, with an N-methyl group. Methods: Tumor xenografts were performed with the human Saos-2 osteosarcoma cell line expressing EGFR. Mice were treated with ZR2002, JS84 or JS61, and the tumor burden was measured with a caliper and CT/PET imaging. Drug metabolism was analyzed with LC-MS. EGFR and ɣ-H2AX phosphorylation were quantified via Western blot analysis and immunohistochemistry. Results: In vivo analysis showed that significant tumor growth inhibition was only achieved when ZR2002 was administered in its naked form. The metabolic dealkylation of JS61 and JS84 did not release sufficient concentrations of ZR2002 for the intratumoral inhibition of P-EGFR or enhanced levels of P-H2AX. Conclusions: The results in toto suggest that intratumoral concentrations of intact ZR2002 are correlated with the highest inhibition of P-EGFR and induction of DNA damage in vivo. ZR2002 may well represent a good drug candidate for the treatment of EGFR-expressing osteosarcoma. Full article
(This article belongs to the Special Issue Translational Research on Solid Tumors)
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13 pages, 2009 KiB  
Article
Overexpression of KMT9α Is Associated with Aggressive Basal-like Muscle-Invasive Bladder Cancer
by Florestan J. Koll, Eric Metzger, Jana Hamann, Anna Ramos-Triguero, Katrin Bankov, Jens Köllermann, Claudia Döring, Felix K. H. Chun, Roland Schüle, Peter J. Wild and Henning Reis
Cells 2023, 12(4), 589; https://doi.org/10.3390/cells12040589 - 11 Feb 2023
Cited by 5 | Viewed by 1603
Abstract
Muscle-invasive bladder cancer (MIBC) is associated with limited response rates to systemic therapy leading to a significant risk of recurrence and death. A recently discovered histone methyltransferase KMT9, acts as an epigenetic regulator of carcinogenesis in different tumor entities. In this study, we [...] Read more.
Muscle-invasive bladder cancer (MIBC) is associated with limited response rates to systemic therapy leading to a significant risk of recurrence and death. A recently discovered histone methyltransferase KMT9, acts as an epigenetic regulator of carcinogenesis in different tumor entities. In this study, we investigated the presence and association of histological and molecular subtypes and their impact on the survival of KMT9α in MIBC. We performed an immunohistochemical (IHC) analysis of KMT9α in 135 MIBC patients undergoing radical cystectomy. KMT9α was significantly overexpressed in the nucleus in MIBC compared to normal urothelium and low-grade urothelial cancer. Using the HTG transcriptome panel, we assessed mRNA expression profiles to determine molecular subtypes and identify differentially expressed genes. Patients with higher nuclear and nucleolar KMT9α expression showed basal/squamous urothelial cancer characteristics confirmed by IHC and differentially upregulated KRT14 expression. We identified a subset of patients with nucleolar expression of KMT9α, which was associated with an increased risk of death in uni- and multivariate analyses (HR 2.28, 95%CI 1.28–4.03, p = 0.005). In conclusion, basal-like MIBC and the squamous histological subtype are associated with high nuclear KMT9α expression. The association with poor survival makes it a potential target for the treatment of bladder cancer. Full article
(This article belongs to the Special Issue Translational Research on Solid Tumors)
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13 pages, 2468 KiB  
Article
Identification and Validation of RELN Mutation as a Response Indicator for Immune Checkpoint Inhibitor Therapy in Melanoma and Non-Small Cell Lung Cancer
by Zhenpeng Li, Xin Wang, Yi Yang, Fuyan Shi, Wenjing Zhang, Qinghua Wang and Suzhen Wang
Cells 2022, 11(23), 3841; https://doi.org/10.3390/cells11233841 - 30 Nov 2022
Cited by 4 | Viewed by 1560
Abstract
Remarkable clinical benefits in several advanced cancers are observed under the treatment of immune checkpoint inhibitor (ICI) agents. However, only a smaller proportion of patients respond to the treatments. Reelin (RELN) is frequently mutated in the cancer genome. In this study, the RELN [...] Read more.
Remarkable clinical benefits in several advanced cancers are observed under the treatment of immune checkpoint inhibitor (ICI) agents. However, only a smaller proportion of patients respond to the treatments. Reelin (RELN) is frequently mutated in the cancer genome. In this study, the RELN mutation association with ICI treatment efficacy in melanoma and non-small cell lung cancer (NSCLC) was elucidated. Data from 631 melanoma and 109 NSCLC patients with both ICI treatment data and pre-treatment mutational profiles were collected. In addition, from the Cancer Genome Atlas (TCGA) project, we also obtained both tumors to explore the immunologic features behind RELN mutations. Melanoma patients with RELN mutations exhibited a favorable ICI survival benefit when compared with wild-type patients (HR: 0.66, 95% CI: 0.51–0.87, p = 0.003). A higher response rate was also noticed in RELN-mutated patients (38.9% vs. 28.3%, p = 0.017). The association of RELN mutations with a preferable immunotherapy outcome and response was further confirmed in NSCLC. Further exploration demonstrated that favorable immunocyte infiltration and immune response signaling pathways were found in patients with RELN mutations. In this study, RELN mutations were identified to connect with a better immune microenvironment and an improved ICI efficacy in melanoma and NSCLC, which provides a potential biomarker for immunological feature evaluation and immunotherapeutic outcome prediction at the molecular level. Full article
(This article belongs to the Special Issue Translational Research on Solid Tumors)
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20 pages, 16281 KiB  
Article
Quantitative Phase Imaging Detecting the Hypoxia-Induced Patterns in Healthy and Neoplastic Human Colonic Epithelial Cells
by Igor Buzalewicz, Monika Mrozowska, Alicja Kmiecik, Michał Kulus, Katarzyna Haczkiewicz-Leśniak, Piotr Dzięgiel, Marzenna Podhorska-Okołów and Łukasz Zadka
Cells 2022, 11(22), 3599; https://doi.org/10.3390/cells11223599 - 14 Nov 2022
Cited by 3 | Viewed by 1954
Abstract
Hypoxia is a frequent phenomenon during carcinogenesis and may lead to functional and structural changes in proliferating cancer cells. Colorectal cancer (CRC) is one of the most common neoplasms in which hypoxia is associated with progression. The aim of this study was to [...] Read more.
Hypoxia is a frequent phenomenon during carcinogenesis and may lead to functional and structural changes in proliferating cancer cells. Colorectal cancer (CRC) is one of the most common neoplasms in which hypoxia is associated with progression. The aim of this study was to assess the optical parameters and microanatomy of CRC and the normal intestinal epithelium cells using the digital holotomography (DHT) method. The examination was conducted on cancer (HT-29, LoVo) and normal colonic cells (CCD-18Co) cultured in normoxic and hypoxic environments. The assessment included optical parameters such as the refractive index (RI) and dry mass as well as the morphological features. Hypoxia decreased the RI in all cells as well as in their cytoplasm, nucleus, and nucleoli. The opposite tendency was noted for spheroid-vesicular structures, where the RI was higher for the hypoxic state. The total volume of hypoxic CCD-18Co and LoVo cells was decreased, while an increase in this parameter was observed for HT-29 cells. Hypoxia increased the radius and cell volume, including the dry mass of the vesicular content. The changes in the optics and morphology of hypoxic cells may suggest the possibility of using DHT in the detection of circulating tumor cells (CTCs). Full article
(This article belongs to the Special Issue Translational Research on Solid Tumors)
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Review

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18 pages, 1878 KiB  
Review
The Promise of Epigenetics Research in the Treatment of Appendiceal Neoplasms
by Luisa Ladel, Wan Ying Tan, Thanushiya Jeyakanthan, Bethsebie Sailo, Anup Sharma and Nita Ahuja
Cells 2023, 12(15), 1962; https://doi.org/10.3390/cells12151962 - 29 Jul 2023
Viewed by 1308
Abstract
Appendiceal cancers (AC) are a rare and heterogeneous group of malignancies. Historically, appendiceal neoplasms have been grouped with colorectal cancers (CRC), and treatment strategies have been modeled after CRC management guidelines due to their structural similarities and anatomical proximity. However, the two have [...] Read more.
Appendiceal cancers (AC) are a rare and heterogeneous group of malignancies. Historically, appendiceal neoplasms have been grouped with colorectal cancers (CRC), and treatment strategies have been modeled after CRC management guidelines due to their structural similarities and anatomical proximity. However, the two have marked differences in biological behavior and treatment response, and evidence suggests significant discrepancies in their respective genetic profiles. In addition, while the WHO classification for appendiceal cancers is currently based on traditional histopathological criteria, studies have demonstrated that histomorphology does not correlate with survival or treatment response in AC. Due to their rarity, appendiceal cancers have not been studied as extensively as other gastrointestinal cancers. However, their incidence has been increasing steadily over the past decade, making it crucial to identify new and more effective strategies for detection and treatment. Recent efforts to map and understand the molecular landscape of appendiceal cancers have unearthed a wealth of information that has made it evident that appendiceal cancers possess a unique molecular profile, distinct from other gastrointestinal cancers. This review focuses on the epigenetic landscape of epithelial appendiceal cancers and aims to provide a comprehensive overview of the current state of knowledge of epigenetic changes across different appendiceal cancer subtypes, highlighting the challenges as well as the promise of employing epigenetics in the quest for the detection of biomarkers, therapeutic targets, surveillance markers, and predictors of treatment response and survival in epithelial appendiceal neoplasms. Full article
(This article belongs to the Special Issue Translational Research on Solid Tumors)
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