From Basic Research to a Clinical Perspective in Oncology

Introduction: Insulin resistance (IR), a key aspect of type 2 diabetes and a defining characteristic of obesity and its associated conditions, emerges as a mechanistic pathway potentially implicated in cancer pathophysiology. This presents an appealing intervention target for cancer patients. The objective of this study is to conduct a systematic review, examining the scientific evidence regarding the impact of physical activity on modifying insulin resistance in individuals with cancer. Methods: The selection criteria were specific: only randomized controlled clinical trials published in the last 13 years and written in English or Spanish were included. The databases utilized for the search included PubMed, Scopus, Cochrane Library, EBSCO, and WEB OF SCIENCE. The protocol for this review was duly registered in the International Register of Systematic Reviews (CRD42023435002). The final search was conducted on 14 May 2023. Results: The outcomes were assessed using the tool proposed by the Cochrane Handbook to evaluate the risk of bias in the included studies. Among the 12 studies incorporated, 8 demonstrated a low risk of bias, two had an unclear risk of bias, and the remaining two showed a high risk of bias. The variety of exercise types used across all studies was extensive, making definitive conclusions challenging. Physical activity was linked to enhanced insulin sensitivity in seven studies, while five studies showed no significant changes in insulin resistance between the intervention and control groups. Importantly, none of the interventions employed in the included studies exhibited adverse effects on the study participants. Conclusions: The role of exercise as a medicine against insulin resistance has been evidenced in many different studies, mostly related to obesity and cardiovascular diseases. Engaging in physical activity could be a healthy option to combat the effects of insulin resistance in cancer patients, although evidence is weak and limited, according to the results of our systemic review. We further found that literature is lacking at the level of optimal doses, timing, and type of exercise. More studies are needed with more defined PA programs in type and length. Full article

Background: The triad of 3D design, 3D printing, and xReality technologies is explored and exploited to collaboratively realize patient-specific products in a timely manner with an emphasis on designs with meta-(bio)materials. Methods: A case study on pelvic reconstruction after oncological resection (osteosarcoma) was selected and conducted to evaluate the applicability and performance of an inter-epistemic workflow and the feasibility and potential of 3D technologies for modeling, optimizing, and materializing individualized orthopedic devices at the point of care (PoC). Results: Image-based diagnosis and treatment at the PoC can be readily deployed to develop orthopedic devices for pre-operative planning, training, intra-operative navigation, and bone substitution. Conclusions: Inter-epistemic symbiosis between orthopedic surgeons and (bio)mechanical engineers at the PoC, fostered by appropriate quality management systems and end-to-end workflows under suitable scientifically amalgamated synergies, could maximize the potential benefits. However, increased awareness is recommended to explore and exploit the full potential of 3D technologies at the PoC to deliver medical devices with greater customization, innovation in design, cost-effectiveness, and high quality. Full article

Enigma protein, encoded by the PDLIM7 gene, is overexpressed in thyroid cancer in a stage-dependent manner, suggesting a potential involvement in the initiation and progression of thyroid cancer. The Enigma interacts with several cellular pathways, including PI3K/AKT, MDM2, and BMP-1. The Enigma is regulated by microRNAs. Specifically, we showed that the Enigma protein upregulation corresponds to the downregulation of Let-7 family genes. There is limited research on the interactions and regulation of the Enigma with other proteins/genes in thyroid cancer tissues, indicating a gap in current knowledge. Our aim is to establish the Enigma as a biomarker. We also aim to study the interacting partners of the Enigma signaling pathways and their probable miRNA regulation in thyroid cancer progression. Using Western blotting, densitometric analysis, immunoprecipitation (IP), and reverse IP, we detected the protein expression and protein–protein interactions in the corresponding papillary thyroid carcinomas (PTCs). Utilizing real-time qPCR assay and Pearson’s correlation test, we highlighted the correlation between PDLIM7 and Let-7g gene expression in the same tissues. The results showed the differential upregulations of the Enigma protein in different stages of PTCs compared to benign tissues along with AKT, VDR, BMP-1, and MDM2 proteins. Loss of DBP was observed in a subset of PTCs. Strong interactions of the Enigma with PI3K/AKT and MDM2 were noted, along with a weaker BMP-1 interaction. Pearson’s correlation coefficient analysis between PDLIM7 and let-7g gene expression was significant (p < 0.05); however, there was a weak inverse correlation (r = −0.27). The study suggests the potential utility of the PDLIM7-qPCR assay as a biomarker for thyroid cancer. The Enigma’s interactions with key signaling pathways may provide valuable insights into the development of thyroid cancer. The study contributes to understanding the molecular mechanisms involving the Enigma protein in thyroid cancer and highlights its potential as a biomarker. Full article

(1) Background: BRAF mutations affect 4–5% of lung adenocarcinomas. This study aimed to analyze the clinicopathological features of lung carcinomas with BRAF mutations, focusing on V600E vs. non-V600E and the presence of co-mutations. (2) Methods: All BRAF-mutated lung carcinomas were retrieved from a molecular diagnostic unit (the reference unit for four different hospitals). The samples were analyzed using next-generation sequencing. Statistical analyses included log-rank tests for overall survival (OS) and progression-free survival (PFS). (3) Results: In total, 60 BRAF-mutated lung carcinomas were retrieved: 24 (40.0%) with V600E and 36 (60.0%) with non-V600E mutations, and 21 (35.0%) with other co-mutations and 39 (65.0%) with only BRAF mutations. Survival data were available for 54/60 (90.0%) cases. Targeted therapy was documented in 11 cases. Patients with V600E mutations exhibited a better prognosis than patients with non-V600E mutations (p = 0.008 for OS, p = 0.018 for PFS); this was confirmed in PFS (p = 0.036) when considering only patients who received no targeted therapy. Patients with co-mutations displayed no prognostic difference compared to patients carrying only BRAF mutations (p = 0.590 for OS, p = 0.938 for PFS). (4) Conclusions: BRAF-mutated lung carcinomas with V600E (40.0%) had a better prognosis than those without V600E. Concomitant co-mutations (35.0%) did not affect the prognosis. Full article