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Novel Molecular Pathways in Oncology

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (30 April 2023) | Viewed by 27569

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Guest Editor
Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, Viale Ferdinando Stagno D’Alcontres, 31-98166 Messina, Italy
Interests: neuroinflammation; neurodegeneration; inflammation; oncology; brain tumor
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Special Issue Information

Dear Colleagues,

Oncology research continues to unveil the molecular signatures that define tumor characteristics and behavior, increasingly shifting its focus on the complex molecular pathways implicated in tumorigenesis, cancer cell proliferation, inflammation and angiogenesis, tissue infiltration and dissemination to distant sites. Novel research should focus on better investigating the molecular mechanisms that promote cancer and on the development of efficient therapeutic and pharmacological interventions. In the current issue, we welcome research and review articles focusing on diverse molecular mechanisms implicated in different steps of carcinogenesis which could serve as therapeutic targets.

Dr. Giovanna Casili
Guest Editor

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Keywords

  • molecular pathway involved in tumorigenesis
  • cancer therapy
  • targeted therapy
  • anticancer drugs
  • brain cancer
  • oral cancer
  • gastrointestinal cancer

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Published Papers (13 papers)

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Research

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19 pages, 3737 KiB  
Article
Repurposing Study of 4-Acyl-1-phenylaminocarbonyl-2-substituted-piperazine Derivatives as Potential Anticancer Agents—In Vitro Evaluation against Breast Cancer Cells
by Emilio Guillén-Mancina, María del Rosario García-Lozano, Estefanía Burgos-Morón, Sarah Mazzotta, Pablo Martínez-Aguado, José Manuel Calderón-Montaño, José Manuel Vega-Pérez, Miguel López-Lázaro, Fernando Iglesias-Guerra and Margarita Vega-Holm
Int. J. Mol. Sci. 2023, 24(23), 17041; https://doi.org/10.3390/ijms242317041 - 1 Dec 2023
Viewed by 1145
Abstract
Breast cancer is the most common type of cancer in women. Although current treatments can increase patient survival, they are rarely curative when the disease is advanced (metastasis). Therefore, there is an urgent need to develop new cytotoxic drugs with a high selectivity [...] Read more.
Breast cancer is the most common type of cancer in women. Although current treatments can increase patient survival, they are rarely curative when the disease is advanced (metastasis). Therefore, there is an urgent need to develop new cytotoxic drugs with a high selectivity toward cancer cells. Since repurposing approved drugs for cancer therapy has been a successful strategy in recent years, in this study, we screened a library of antiviral piperazine-derived compounds as anticancer agents. The compounds included a piperazine ring and aryl urea functions, which are privileged structures present in several anti-breast cancer drugs. The selective cytotoxic activity of a set of thirty-four 4-acyl-2-substituted piperazine urea derivatives against MCF7 breast cancer cells and MCF 10A normal breast cells was determined. Compounds 31, 32, 35, and 37 showed high selective anticancer activity against breast cancer cells and were also tested against another common type of cancer, non-small cell lung cancer (A549 lung cancer cells versus MRC-5 lung normal cells). Compounds 35 and 37 also showed selectivity against lung cancer cells. These results suggest that compounds 35 and 37 may be promising hit compounds for the development of new anticancer agents. Full article
(This article belongs to the Special Issue Novel Molecular Pathways in Oncology)
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15 pages, 5504 KiB  
Article
Translocation of Methionine Adenosyl Transferase MAT2A and Its Prognostic Relevance for Liver Hepatocellular Carcinoma
by Pei-Yi Chu, Dev-Aur Chou, Po-Ming Chen and En-Pei Isabel Chiang
Int. J. Mol. Sci. 2023, 24(10), 9103; https://doi.org/10.3390/ijms24109103 - 22 May 2023
Viewed by 2496
Abstract
Methionine adenosyl transferases (MATs) catalyze the synthesis of the biological methyl donor adenosylmethionine (SAM). Dysregulation of MATs has been associated with carcinogenesis in humans. We previously found that downregulation of the MAT1A gene enriches the protein-associated translation process and worsens liver hepatocellular carcinoma [...] Read more.
Methionine adenosyl transferases (MATs) catalyze the synthesis of the biological methyl donor adenosylmethionine (SAM). Dysregulation of MATs has been associated with carcinogenesis in humans. We previously found that downregulation of the MAT1A gene enriches the protein-associated translation process and worsens liver hepatocellular carcinoma (LIHC) prognosis. We also discovered that subcellular localization of the MAT2A protein has independently prognostic relevance in breast cancer patients. The present study aimed to examined the clinical relevance of MAT2A translocation in human LIHC. Essential methionine cycle gene expressions in TCGA LIHC datasets were analyzed using Gene Expression Profiling Interactive Analysis 2 (GEPIA2). The protein expression pattern of MAT2A was determined in the tissue array of our own LIHC cohort (n = 261) using immuno-histochemistry, and the prognostic relevance of MAT2A protein’s subcellular localization expression was examined using Kaplan–Meier survival curves. LIHC patients with higher MAT2A mRNA expression had a worse survival rate (p = 0.0083). MAT2A protein immunoreactivity was observed in both cytoplasm and nucleus fractions in the tissue array. Tumor tissues had elevated MAT2A protein expression in both cytoplasm and nucleus compared to their adjacent normal tissues. A higher cytoplasmic to nuclear MAT2A protein expression ratio (C/N) was found in female LIHC patients compared to that of male patients (p = 0.047). Kaplan–Meier survival curves showed that a lower MAT2A C/N correlated with poor overall survival in female LIHC patients (10-year survival rate: 29.2% vs. 68.8%, C/N ≤ 1.0 vs. C/N > 1.0, log-rank p = 0.004). Moreover, we found that specificity protein 1 (SP1) may have a potential interaction with nuclear MAT2A protein, using protein–protein interaction; this we found using the GeneMANIA algorithm. We explored the possible protective effects of the estrogen axis in LIHC using the Human Protein Atlas (HPA), and found evidence supporting a possible protective effect of estrogen-related protein ESSRG in LIHC. The localization of SP1 and MAT2 appeared to be inversely associated with ESRRG expression in LIHC. The present study demonstrated the translocation of MAT2A and its prognostic relevance in female LIHC patients. Our findings suggest the potential of estrogen in SP1 regulation and localization of MAT2A, as therapeutic modalities against in female LIHC patients. Full article
(This article belongs to the Special Issue Novel Molecular Pathways in Oncology)
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20 pages, 2444 KiB  
Article
Microphthalmia-Associated Transcription Factor: A Differentiation Marker in Uveal Melanoma
by Maria Chiara Gelmi, Robert M. Verdijk, Laurien E. Houtzagers, Pieter A. van der Velden, Wilma G. M. Kroes, Gregorius P. M. Luyten, T. H. Khanh Vu and Martine J. Jager
Int. J. Mol. Sci. 2023, 24(10), 8861; https://doi.org/10.3390/ijms24108861 - 16 May 2023
Cited by 1 | Viewed by 1442
Abstract
Microphthalmia-associated transcription factor (MITF) is an important regulator of melanogenesis and melanocyte development. In cutaneous melanoma, MITF loss has been linked to an increased expression of stem cell markers, a shift in epithelial-to-mesenchymal transition (EMT)-related factors, and increased inflammation. We explored the role [...] Read more.
Microphthalmia-associated transcription factor (MITF) is an important regulator of melanogenesis and melanocyte development. In cutaneous melanoma, MITF loss has been linked to an increased expression of stem cell markers, a shift in epithelial-to-mesenchymal transition (EMT)-related factors, and increased inflammation. We explored the role of MITF in Uveal Melanoma (UM) using a cohort of 64 patients enucleated at the Leiden University Medical Center. We analysed the relation between MITF expression and clinical, histopathological and genetic features of UM, as well as survival. We performed differential gene expression and gene set enrichment analysis using mRNA microarray data, comparing MITF-low with MITF-high UM. MITF expression was lower in heavily pigmented UM than in lightly pigmented UM (p = 0.003), which we confirmed by immunohistochemistry. Furthermore, MITF was significantly lower in UM with monosomy 3/BAP1 loss than in those with disomy 3/no BAP1 loss (p < 0.001) and with 8q gain/amplification 8q (p = 0.02). Spearman correlation analysis showed that a low MITF expression was associated with an increase in inflammatory markers, hallmark pathways involved in inflammation, and epithelial-mesenchymal transition. Similar to the situation in cutaneous melanoma, we propose that MITF loss in UM is related to de-differentiation to a less favourable EMT profile and inflammation. Full article
(This article belongs to the Special Issue Novel Molecular Pathways in Oncology)
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14 pages, 2784 KiB  
Article
Compositional Analysis of Glycosaminoglycans in Different Lung Cancer Types—A Pilot Study
by Domonkos Pál, Gábor Tóth, Simon Sugár, Kata Dorina Fügedi, Dániel Szabó, Ilona Kovalszky, Dávid Papp, Gitta Schlosser, Csaba Tóth, Tamás Tornóczky, László Drahos and Lilla Turiák
Int. J. Mol. Sci. 2023, 24(8), 7050; https://doi.org/10.3390/ijms24087050 - 11 Apr 2023
Cited by 4 | Viewed by 1853
Abstract
Lung cancer is one of the most commonly diagnosed cancer types. Studying the molecular changes that occur in lung cancer is important to understand tumor formation and identify new therapeutic targets and early markers of the disease to decrease mortality. Glycosaminoglycan chains play [...] Read more.
Lung cancer is one of the most commonly diagnosed cancer types. Studying the molecular changes that occur in lung cancer is important to understand tumor formation and identify new therapeutic targets and early markers of the disease to decrease mortality. Glycosaminoglycan chains play important roles in various signaling events in the tumor microenvironment. Therefore, we have determined the quantity and sulfation characteristics of chondroitin sulfate and heparan sulfate in formalin-fixed paraffin-embedded human lung tissue samples belonging to different lung cancer types as well as tumor adjacent normal areas. Glycosaminoglycan disaccharide analysis was performed using HPLC-MS following on-surface lyase digestion. Significant changes were identified predominantly in the case of chondroitin sulfate; for example, the total amount was higher in tumor tissue compared to the adjacent normal tissue. We also observed differences in the degree of sulfation and relative proportions of individual chondroitin sulfate disaccharides between lung cancer types and adjacent normal tissue. Furthermore, the differences in the 6-O-/4-O-sulfation ratio of chondroitin sulfate were different between the lung cancer types. Our pilot study revealed that further investigation of the role of chondroitin sulfate chains and enzymes involved in their biosynthesis is an important aspect of lung cancer research. Full article
(This article belongs to the Special Issue Novel Molecular Pathways in Oncology)
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12 pages, 4070 KiB  
Article
High Expression of Tetraspanin 5 as a Prognostic Marker of Colorectal Cancer
by Sanghyun Roh, Sooyoun Kim, Inpyo Hong, Minho Lee, Han Jo Kim, Tae Sung Ahn, Dong Hyun Kang, Moo-Jun Baek, Hyoung Jong Kwak, Chang-Jin Kim and Dongjun Jeong
Int. J. Mol. Sci. 2023, 24(7), 6476; https://doi.org/10.3390/ijms24076476 - 30 Mar 2023
Cited by 2 | Viewed by 1517
Abstract
Cancer is a major disease and the leading cause of death worldwide, with colorectal cancer (CRC) being the third-most common cancer in Korea. The survival rate associated with CRC reduces as the disease stage increases. Therefore, its early detection and treatment can greatly [...] Read more.
Cancer is a major disease and the leading cause of death worldwide, with colorectal cancer (CRC) being the third-most common cancer in Korea. The survival rate associated with CRC reduces as the disease stage increases. Therefore, its early detection and treatment can greatly increase patient survival rates. In this study, we identified the tetraspanin 5 (TSPAN5) gene as an important biomarker for predicting the prognosis of patients with CRC. A TMA slide was used for statistical analysis. pN and clinical stage were found to be significant factors according to chi-square analysis, whereas pT, pN, metastasis, clinical stage, and TSPAN5 expression were significant according to Cox regression analysis. In order to prove the usefulness of TSPAN5, which is overexpressed in patients with metastatic CRC, as a biomarker, proliferation, migration, invasion, and tumorigenicity were examined using cell lines inhibited using small interfering RNA. The evaluations confirmed that TSPAN5 suppression, in turn, suppressed proliferation, migration, invasion, and tumorigenesis, which are characteristic of cancer cells. Therefore, the evaluation of TSPAN5 expression may help observe the prognosis of CRC and determine an appropriate treatment method for patients with CRC. Full article
(This article belongs to the Special Issue Novel Molecular Pathways in Oncology)
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14 pages, 2312 KiB  
Article
Cancer Cell-Derived PDGFB Stimulates mTORC1 Activation in Renal Carcinoma
by Asmaa Y. Abuhamad, Nurul Nadia Mohamad Zamberi, Sakari Vanharanta, Siti Nur Hasanah Mohd Yusuf, M. Aiman Mohtar and Saiful Effendi Syafruddin
Int. J. Mol. Sci. 2023, 24(7), 6447; https://doi.org/10.3390/ijms24076447 - 29 Mar 2023
Cited by 2 | Viewed by 1548
Abstract
Clear cell renal cell carcinoma (ccRCC) is a hypervascular tumor that is characterized by bi-allelic inactivation of the VHL tumor suppressor gene and mTOR signalling pathway hyperactivation. The pro-angiogenic factor PDGFB, a transcriptional target of super enhancer-driven KLF6, can activate the mTORC1 signalling [...] Read more.
Clear cell renal cell carcinoma (ccRCC) is a hypervascular tumor that is characterized by bi-allelic inactivation of the VHL tumor suppressor gene and mTOR signalling pathway hyperactivation. The pro-angiogenic factor PDGFB, a transcriptional target of super enhancer-driven KLF6, can activate the mTORC1 signalling pathway in ccRCC. However, the detailed mechanisms of PDGFB-mediated mTORC1 activation in ccRCC have remained elusive. Here, we investigated whether ccRCC cells are able to secrete PDGFB into the extracellular milieu and stimulate mTORC1 signalling activity. We found that ccRCC cells secreted PDGFB extracellularly, and by utilizing KLF6- and PDGFB-engineered ccRCC cells, we showed that the level of PDGFB secretion was positively correlated with the expression of intracellular KLF6 and PDGFB. Moreover, the reintroduction of either KLF6 or PDGFB was able to sustain mTORC1 signalling activity in KLF6-targeted ccRCC cells. We further demonstrated that conditioned media of PDGFB-overexpressing ccRCC cells was able to re-activate mTORC1 activity in KLF6-targeted cells. In conclusion, cancer cell-derived PDGFB can mediate mTORC1 signalling pathway activation in ccRCC, further consolidating the link between the KLF6-PDGFB axis and the mTORC1 signalling pathway activity in ccRCC. Full article
(This article belongs to the Special Issue Novel Molecular Pathways in Oncology)
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18 pages, 11702 KiB  
Article
Generation of a Perfusable 3D Lung Cancer Model by Digital Light Processing
by Yikun Mei, Dongwei Wu, Johanna Berg, Beatrice Tolksdorf, Viola Roehrs, Anke Kurreck, Thomas Hiller and Jens Kurreck
Int. J. Mol. Sci. 2023, 24(7), 6071; https://doi.org/10.3390/ijms24076071 - 23 Mar 2023
Cited by 6 | Viewed by 2848
Abstract
Lung cancer still has one of the highest morbidity and mortality rates among all types of cancer. Its incidence continues to increase, especially in developing countries. Although the medical field has witnessed the development of targeted therapies, new treatment options need to be [...] Read more.
Lung cancer still has one of the highest morbidity and mortality rates among all types of cancer. Its incidence continues to increase, especially in developing countries. Although the medical field has witnessed the development of targeted therapies, new treatment options need to be developed urgently. For the discovery of new drugs, human cancer models are required to study drug efficiency in a relevant setting. Here, we report the generation of a non-small cell lung cancer model with a perfusion system. The bioprinted model was produced by digital light processing (DLP). This technique has the advantage of including simulated human blood vessels, and its simple assembly and maintenance allow for easy testing of drug candidates. In a proof-of-concept study, we applied gemcitabine and determined the IC50 values in the 3D models and 2D monolayer cultures and compared the response of the model under static and dynamic cultivation by perfusion. As the drug must penetrate the hydrogel to reach the cells, the IC50 value was three orders of magnitude higher for bioprinted constructs than for 2D cell cultures. Compared to static cultivation, the viability of cells in the bioprinted 3D model was significantly increased by approximately 60% in the perfusion system. Dynamic cultivation also enhanced the cytotoxicity of the tested drug, and the drug-mediated apoptosis was increased with a fourfold higher fraction of cells with a signal for the apoptosis marker caspase-3 and a sixfold higher fraction of cells positive for PARP-1. Altogether, this easily reproducible cancer model can be used for initial testing of the cytotoxicity of new anticancer substances. For subsequent in-depth characterization of candidate drugs, further improvements will be necessary, such as the generation of a multi-cell type lung cancer model and the lining of vascular structures with endothelial cells. Full article
(This article belongs to the Special Issue Novel Molecular Pathways in Oncology)
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13 pages, 494 KiB  
Article
Pilot Study on the Impact of Polymorphisms Linked to Multi-Kinase Inhibitor Metabolism on Lenvatinib Side Effects in Patients with Advanced Thyroid Cancer
by Silvia Cantara, Cristina Dalmiglio, Carlotta Marzocchi, Alfonso Sagnella, Lucia Brilli, Andrea Trimarchi, Fabio Maino, Laura Valerio and Maria Grazia Castagna
Int. J. Mol. Sci. 2023, 24(6), 5496; https://doi.org/10.3390/ijms24065496 - 13 Mar 2023
Cited by 2 | Viewed by 1652
Abstract
Multi-kinase inhibitors (MKIs) represent the best therapeutic option in advanced thyroid cancer patients. The therapeutic efficacy and toxicity of MKIs are very heterogeneous and are difficult to predict before starting treatment. Moreover, due to the development of severe adverse events, it is necessary [...] Read more.
Multi-kinase inhibitors (MKIs) represent the best therapeutic option in advanced thyroid cancer patients. The therapeutic efficacy and toxicity of MKIs are very heterogeneous and are difficult to predict before starting treatment. Moreover, due to the development of severe adverse events, it is necessary to interrupt the therapy some patients. Using a pharmacogenetic approach, we evaluated polymorphisms in genes coding for proteins involved with the absorption and elimination of the drug in 18 advanced thyroid cancer patients treated with lenvatinib, and correlated the genetic background with (1) diarrhea, nausea, vomiting and epigastric pain; (2) oral mucositis and xerostomia; (3) hypertension and proteinuria; (4) asthenia; (5) anorexia and weight loss; (6) hand foot syndrome. Analyzed variants belong to cytochrome P450 (CYP3A4 rs2242480 and rs2687116 and CYP3A5 rs776746) genes and to ATP-binding cassette transporters (ABCB1 rs1045642, rs2032582 and rs2235048 and ABCG2 rs2231142). Our results suggest that the GG genotype for rs2242480 in CYP3A4 and CC genotype in rs776746 for CYP3A5 were both associated with the presence of hypertension. Being heterozygous for SNPs in the ABCB1 gene (rs1045642 and 2235048) implicated a higher grade of weight loss. The ABCG2 rs2231142 statistically correlated with a higher extent of mucositis and xerostomia (CC genotype). Heterozygous and rare homozygous genotypes for rs2242480 in CYP3A4 and for rs776746 for CYP3A5 were found to be statistically linked to a worse outcome. Evaluating the genetic profile before starting lenvatinib treatment may help to predict the occurrence and grade of some side effects, and may contribute to improving patient management. Full article
(This article belongs to the Special Issue Novel Molecular Pathways in Oncology)
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14 pages, 4887 KiB  
Article
Therapeutic Potential of Dimethyl Fumarate in Counteract Oral Squamous Cell Carcinoma Progression by Modulating Apoptosis, Oxidative Stress and Epithelial–Mesenchymal Transition
by Rossella Basilotta, Marika Lanza, Alessia Filippone, Giovanna Casili, Deborah Mannino, Federica De Gaetano, Giulia Chisari, Lorenzo Colarossi, Gianmarco Motta, Michela Campolo, Salvatore Cuzzocrea, Irene Paterniti and Emanuela Esposito
Int. J. Mol. Sci. 2023, 24(3), 2777; https://doi.org/10.3390/ijms24032777 - 1 Feb 2023
Cited by 3 | Viewed by 1949
Abstract
Oral squamous cell carcinoma (OSCC) is a common human tumor, that originates from buccal mucosa and the tongue, associated with a high mortality rate. Currently, the treatment for OSCC involves surgery, chemotherapy and radiotherapy; however, survival outcomes for OSCC patients remain poor. For [...] Read more.
Oral squamous cell carcinoma (OSCC) is a common human tumor, that originates from buccal mucosa and the tongue, associated with a high mortality rate. Currently, the treatment for OSCC involves surgery, chemotherapy and radiotherapy; however, survival outcomes for OSCC patients remain poor. For this reason, it is necessary to investigate new therapeutic strategies to counteract the progression of OSCC. In this study, we aimed to evaluate the role of dimethyl fumarate (DMF) in modulation of OSCC progression, both in vitro and in an in vivo orthotopic xenograft model. In vitro results revealed that DMF was able to reduce the expression of anti-apoptotic factors as BCL-2 and increased the expression of pro-apoptotic factors as Bax, Caspase-3 and BID. DMF appears to be involved in the modulation of oxidative stress mediators, such as MnSOD and HO-1. Furthermore, DMF showed to reduce the migratory ability of tumor cells and to modulate the expression of markers of epithelial-mesenchymal transition (EMT), as N-cadherin and E-cadherin. The in vivo study confirmed the data obtained in vitro significantly decreasing tumor mass and also reducing oxidative stress and apoptosis. Therefore, based on these results, the use of DMF could be considered a promising strategy to counteract oral cancer progression. Full article
(This article belongs to the Special Issue Novel Molecular Pathways in Oncology)
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19 pages, 6766 KiB  
Article
Mining TCGA Database for Genes with Prognostic Value in Breast Cancer
by Alexandru Filippi and Maria-Magdalena Mocanu
Int. J. Mol. Sci. 2023, 24(2), 1622; https://doi.org/10.3390/ijms24021622 - 13 Jan 2023
Cited by 4 | Viewed by 2596
Abstract
The aim of the study was to use transcriptomics data to identify genes associated with advanced/aggressive breast cancer and their effect on survival outcomes. We used the publicly available The Cancer Genome Atlas (TCGA) database to obtain RNA sequence data from patients with [...] Read more.
The aim of the study was to use transcriptomics data to identify genes associated with advanced/aggressive breast cancer and their effect on survival outcomes. We used the publicly available The Cancer Genome Atlas (TCGA) database to obtain RNA sequence data from patients with less than five years survival (Poor Prognosis, n = 101), patients with greater than five years survival (Good Prognosis, n = 200), as well as unpaired normal tissue data (normal, n = 105). The data analyses performed included differential expression between groups and selection of subsets of genes, gene ontology, cell enrichment analysis, and survival analyses. Gene ontology results showed significantly reduced enrichment in gene sets related to tumor immune microenvironment in Poor Prognosis and cell enrichment analysis confirmed significantly reduced numbers of macrophages M1, CD8 T cells, plasma cells and dendritic cells in samples in the Poor Prognosis samples compared with Good Prognosis. A subset of 742 genes derived from differential expression analysis as well as genes coding for immune checkpoint molecules was evaluated for their effect on overall survival. In conclusion, this study may contribute to the better understanding of breast cancer transcriptomics and provide possible targets for further research and eventual therapeutic interventions. Full article
(This article belongs to the Special Issue Novel Molecular Pathways in Oncology)
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13 pages, 3197 KiB  
Article
Tumor Targeting by Conjugation of Chlorambucil with Zwitterionic Near-Infrared Fluorophore for Cancer Phototherapy
by Gayoung Jo, Eun Jeong Kim and Hoon Hyun
Int. J. Mol. Sci. 2022, 23(22), 14093; https://doi.org/10.3390/ijms232214093 - 15 Nov 2022
Cited by 3 | Viewed by 1394
Abstract
Improving the tumor targeting of anticancer drugs to minimize systemic exposure remains challenging. The chemical conjugation of anticancer drugs with various near-infrared (NIR) fluorophores may provide an effective approach to improve NIR laser-induced cancer phototherapy. Towards this end, the selection of NIR fluorophores [...] Read more.
Improving the tumor targeting of anticancer drugs to minimize systemic exposure remains challenging. The chemical conjugation of anticancer drugs with various near-infrared (NIR) fluorophores may provide an effective approach to improve NIR laser-induced cancer phototherapy. Towards this end, the selection of NIR fluorophores conjugated with hydrophobic anticancer drugs is an important consideration for targeted cancer photothermal therapy (PTT). In this study, a highly water-soluble zwitterionic NIR fluorophore (ZW800) was prepared to conjugate with a water-insoluble anticancer drug, chlorambucil (CLB), to improve tumor targeting, in vivo biodistribution, and PTT performance. The in vivo results using an HT-29 xenograft mouse model demonstrated that the CLB-ZW800 conjugate not only exhibited high tumor accumulation within 4 h after injection, but also showed rapid body clearance behavior for less systemic toxicity. Furthermore, the tumor tissue targeted by the CLB-ZW800 conjugate was exposed to 808 nm NIR laser irradiation to generate photothermal energy and promote apoptotic cell death for the effective PTT of cancer. Therefore, this study provides a feasible strategy for developing bifunctional PTT agents capable of tumor-targeted imaging and phototherapy by the conjugation of small molecule drugs with the versatile zwitterionic NIR fluorophore. Full article
(This article belongs to the Special Issue Novel Molecular Pathways in Oncology)
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Review

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39 pages, 7942 KiB  
Review
Targeting Breast Cancer: An Overlook on Current Strategies
by Domenico Iacopetta, Jessica Ceramella, Noemi Baldino, Maria Stefania Sinicropi and Alessia Catalano
Int. J. Mol. Sci. 2023, 24(4), 3643; https://doi.org/10.3390/ijms24043643 - 11 Feb 2023
Cited by 21 | Viewed by 3847
Abstract
Breast cancer (BC) is one of the most widely diagnosed cancers and a leading cause of cancer death among women worldwide. Globally, BC is the second most frequent cancer and first most frequent gynecological one, affecting women with a relatively low case-mortality rate. [...] Read more.
Breast cancer (BC) is one of the most widely diagnosed cancers and a leading cause of cancer death among women worldwide. Globally, BC is the second most frequent cancer and first most frequent gynecological one, affecting women with a relatively low case-mortality rate. Surgery, radiotherapy, and chemotherapy are the main treatments for BC, even though the latter are often not aways successful because of the common side effects and the damage caused to healthy tissues and organs. Aggressive and metastatic BCs are difficult to treat, thus new studies are needed in order to find new therapies and strategies for managing these diseases. In this review, we intend to give an overview of studies in this field, presenting the data from the literature concerning the classification of BCs and the drugs used in therapy for the treatment of BCs, along with drugs in clinical studies. Full article
(This article belongs to the Special Issue Novel Molecular Pathways in Oncology)
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16 pages, 1877 KiB  
Review
The Intracellular and Secreted Sides of Osteopontin and Their Putative Physiopathological Roles
by Ana Clara Santos da Fonseca Bastos, Amanda Vitória Pampolha Gomes, Gabriela Ribeiro Silva, Mariana Emerenciano, Luciana Bueno Ferreira and Etel Rodrigues Pereira Gimba
Int. J. Mol. Sci. 2023, 24(3), 2942; https://doi.org/10.3390/ijms24032942 - 2 Feb 2023
Cited by 12 | Viewed by 2650
Abstract
Classically, osteopontin (OPN) has been described as a secreted glycophosprotein. Indeed, most data concerning its physiological and pathological roles are mainly related to the secreted OPN (sOPN). However, there are several instances in which intracellular OPN (iOPN) has been described, presenting some specific [...] Read more.
Classically, osteopontin (OPN) has been described as a secreted glycophosprotein. Indeed, most data concerning its physiological and pathological roles are mainly related to the secreted OPN (sOPN). However, there are several instances in which intracellular OPN (iOPN) has been described, presenting some specific roles in distinct experimental models, such as in the immune system, cancer cells, and neurological disorders. We herein aimed to highlight and discuss some of these secreted and intracellular roles of OPN and their putative clinical and biological impacts. Moreover, by consolidating data from the OPN protein database, we also analyzed the occurrence of signal peptide (SP) sequences and putative subcellular localization, especially concerning currently known OPN splicing variants (OPN-SV). Comprehending the roles of OPN in its distinct cellular and tissue environments may provide data regarding the additional applications of this protein as biomarkers and targets for therapeutic purposes, besides further describing its pleiotropic roles. Full article
(This article belongs to the Special Issue Novel Molecular Pathways in Oncology)
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