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Onco, Volume 2, Issue 1 (March 2022) – 4 articles

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20 pages, 1755 KiB  
Review
Akt/mTOR Activation in Lung Cancer Tumorigenic Regulators and Their Potential Value as Biomarkers
by Carolina Sousa, Beatriz Silva-Lima and Mafalda Videira
Onco 2022, 2(1), 36-55; https://doi.org/10.3390/onco2010004 - 25 Feb 2022
Cited by 2 | Viewed by 3897
Abstract
The high incidence and modest therapeutic outcomes of lung cancer have prompted the identification of cell molecular targets/biomarkers within the complex networks of interactions involved in cell malignancy. Most of the EMT-related regulatory mediators underline patients’ biologic variations, therapeutic refractory events, and tumor [...] Read more.
The high incidence and modest therapeutic outcomes of lung cancer have prompted the identification of cell molecular targets/biomarkers within the complex networks of interactions involved in cell malignancy. Most of the EMT-related regulatory mediators underline patients’ biologic variations, therapeutic refractory events, and tumor cell heterogeneity. Patient stratification based on the understanding of the relevant pathways, such as the PI3K/Akt axis crucial in EMT initiation, could favorably alter disease management. Significant clinical advantage could be expected when overexpressed Akt tyrosine kinase (Akt2) is addressed as a malignant biomarker to guide clinical management decisions, improving prognosis in lung cancer patients. Moreover, one should not miss the opportunity of using it as a druggable target aiming at the inhibition of the downstream complexity that underlies cell proliferation and survival, expression of stemness markers and drug resistance. The value of mTOR, as a downstream target of Akt, and the further activation of EMT transcription factors Twist, Snail and Zeb1 are revisited in this review. An in-depth state-of-the-art assessment provides evidence of its role in the mechanistic inhibition of epithelial markers, such as E-cadherin and miR-200, while inducing the expression of the mesenchymal ones, such as vimentin, N-cadherin, and miR-21. Lastly, evidence suggesting another transcription factor, FOXM1, as the link between the PI3K/Akt and Wnt/β-catenin pathways, prompting cell metabolism through the regulation of p70S6K, is analyzed. A more realistic approach is advised to address unmet clinical needs and support decision making at a clinical level. Taking into consideration several complex intracellular interactions might further improve patient stratification and result in better outcomes. Full article
(This article belongs to the Special Issue Feature Papers in Onco)
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2 pages, 148 KiB  
Editorial
Targeting Abnormal Cell Cycle in Cancer: A Preface to the Special Issue
by Chiaki Takahashi and Jun-ya Kato
Onco 2022, 2(1), 34-35; https://doi.org/10.3390/onco2010003 - 13 Jan 2022
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Abstract
The accelerated cell cycle progression is one of the hallmarks of human cancer [...] Full article
(This article belongs to the Special Issue Targeting Abnormal Cell Cycle in Cancer)
15 pages, 2879 KiB  
Article
Optimizing the Pharmacological and Optical Dosimetry for Photodynamic Therapy with Methylene Blue and Nanoliposomal Benzoporphyrin on Pancreatic Cancer Spheroids
by Tristan Le Clainche, Nazareth Milagros Carigga Gutierrez, Núria Pujol-Solé, Jean-Luc Coll and Mans Broekgaarden
Onco 2022, 2(1), 19-33; https://doi.org/10.3390/onco2010002 - 07 Jan 2022
Cited by 4 | Viewed by 3051
Abstract
Photodynamic therapy (PDT) is a cancer treatment that relies on the remote-controlled activation of photocatalytic dyes (photosensitizers) in cancer tissues. To effectively treat cancer, a variety of pharmacological and optical parameters require optimization, which are dependent on the photosensitizer type. As most photosensitizers [...] Read more.
Photodynamic therapy (PDT) is a cancer treatment that relies on the remote-controlled activation of photocatalytic dyes (photosensitizers) in cancer tissues. To effectively treat cancer, a variety of pharmacological and optical parameters require optimization, which are dependent on the photosensitizer type. As most photosensitizers are hydrophobic molecules, nanoliposomes are frequently used to increase the biocompatibility of these therapeutics. However, as nanoliposomes can influence the therapeutic performance of photosensitizers, the most suitable treatment parameters need to be elucidated. Here, we evaluate the efficacy of PDT on spheroid cultures of PANC-1 and MIA PaCa-2 pancreatic cancer cells. Two strategies to photosensitize the pancreatic microtumors were selected, based on either nanoliposomal benzoporphyrin derivative (BPD), or non-liposomal methylene blue (MB). Using a comprehensive image-based assay, our findings show that the PDT efficacy manifests in distinct manners for each photosensitizer. Moreover, the efficacy of each photosensitizer is differentially influenced by the photosensitizer dose, the light dose (radiant exposure or fluence in J/cm2), and the dose rate (fluence rate in mW/cm2). Taken together, our findings illustrate that the most suitable light dosimetry for PDT strongly depends on the selected photosensitization strategy. The PDT dose parameters should therefore always be carefully optimized for different models of cancer. Full article
(This article belongs to the Special Issue Feature Papers in Onco)
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18 pages, 2219 KiB  
Article
Core Needle Biopsy Enhances the Activity of the CCL2/CCR2 Pathway in the Microenvironment of Invasive Breast Cancer
by Marja Heiskala, Kristiina Joensuu and Päivi Heikkilä
Onco 2022, 2(1), 1-18; https://doi.org/10.3390/onco2010001 - 30 Dec 2021
Cited by 1 | Viewed by 2413
Abstract
The use of core needle biopsy (CNB) as a means to verify malignancy preoperatively is a paradigm in current breast cancer care, and the risk of enhancing tumor development by this procedure has been considered insignificant. Experimental work in mice has shown preoperative [...] Read more.
The use of core needle biopsy (CNB) as a means to verify malignancy preoperatively is a paradigm in current breast cancer care, and the risk of enhancing tumor development by this procedure has been considered insignificant. Experimental work in mice has shown preoperative biopsies to increase tumor supportive elements in the microenvironment, whereas, in humans, the impact of CNB on the host’s immunologic response has not been investigated. In this pilot study, we compared the expression of CCL2/CCR2 pathway components at the protein level in samples from CNBs to those from the corresponding resected tumors from 52 patients with primary breast cancer. We found an increased expression of CD163, CD14 and CCR2 in monocytes/macrophages and a slight decrease of CCL2 in the malignant epithelium in the tumors after the biopsy. The increased infiltration of immunosuppressive monocytes/macrophages and the decreased tumor cell CCL2 expression, presumably due to the CCR2 availability-dependent CCL2 internalization, suggest that CNB enhances the activity of the CCL2/CCR2 pathway, and this finding warrants confirmatory examination. The switch in the context-dependent role of CCL2 on the polarization of macrophages may lead to increased tumor supportive function both locally and in the peripheral immune machinery. The future directions in breast cancer should include early interventions to support the tumor surveillance of the host. Full article
(This article belongs to the Special Issue Feature Papers in Onco)
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