Objective: To investigate the impact of a prior cervical excisional procedure on the oncologic outcomes of patients with apparent early-stage cervical carcinoma undergoing radical hysterectomy. Methods: The National Cancer Database (2004–2015) was accessed, and patients with FIGO 2009 stage IB1 cervical cancer who had a radical hysterectomy with at least 10 lymph nodes (LNs) removed and a known surgical approach were identified. Patients who did and did not undergo a prior cervical excisional procedure (within 3 months of hysterectomy) were selected for further analysis. Overall survival (OS) was evaluated following the generation of Kaplan–Meier curves and compared with the log-rank test. A Cox model was constructed to control a priori-selected confounders. Results: A total of 3159 patients were identified; 37.1% (n = 1171) had a prior excisional procedure. These patients had lower rates of lymphovascular invasion (29.2% vs. 34.9%, p = 0.014), positive LNs (6.7% vs. 12.7%, p < 0.001), and a tumor size >2 cm (25.7% vs. 56%, p < 0.001). Following stratification by tumor size, the performance of an excisional procedure prior to radical hysterectomy was associated with better OS even after controlling for confounders (aHR: 0.45, 95% CI: 0.30, 0.66). The rate of minimally invasive surgery was higher among patients who had a prior excisional procedure (61.5% vs. 53.2%, p < 0.001). For these patients, performance of minimally invasive radical hysterectomy was not associated with worse OS (aHR: 1.37, 95% CI: 0.66, 2.82). Conclusions: For patients undergoing radical hysterectomy, preoperative cervical excision may be associated with a survival benefit. For patients who had a prior excisional procedure, minimally invasive radical hysterectomy was not associated with worse overall survival. Full article

Background and Objectives: Heart rate variability (HRV) is defined as a physiological variation in duration between sinus beats. The aim of this study was to research and analyze the HRV between various groups of patients. Materials and Methods: A retrospective study was conducted in an outpatient setting. Patients who had undergone a tilt-table test were selected for this study and were divided into three groups based on their self-reported health anamnesis: group 1 (n = 84, mean age 45.8 ± 17.8) consisted of patients with no known orthostatic intolerance or neurodegenerative disease, group 2 consisted of patients with a known or suspected orthostatic intolerance (n = 50, mean age 46.5 ± 18.6), and group 3 consisted of patients with a known or suspected neurodegenerative disorder (n = 29, mean age 55.6 ± 20.4). During the tilt-table test, HRV frequency-domain parameters—normalized low frequency (LFnu) and high frequency (HFnu), absolute powers—absolute low frequency (LF-RRI), absolute high frequency (HF-RRI), and LF/HF ratio—were recorded during 5 min rest in the supine position. Results: Group 1 had a reduced LFnu at 52.93% (SD: 18.00) compared to group 2 at 58.57% (18.06) and group 3 at 61.80% (SD: 17.74), and group 1 had increased HFnu: group 1—47.08% (SD: 17.97), group 2—41.41% (SD: 18.03), and group 3—38.16% (SD: 14.7). LFnu and HFnu differences were statistically significant (p < 0.05). LF-RRI was reported as follows: group 1—531.32 ms² (SD: 578.57), group 2—346.2 ms² (SD: 447.96), and group 3—143.21 ms² (SD: 166.96). HF-RRI was reported as follows: group 1—835.87 ms² (SD: 1625.42), group 2—297.46 ms² (SD: 507.15), and group 3—70.83 ms² (SD: 75.67). LF-RRI and HF-RRI comparisons between groups were statistically significant (p < 0.001). LF/HF ratios were reported as follows: group 1—1.91 (SD: 2.29), group 2—2.43 (SD: 2.33), and group 3–2.54 (SD: 2.17). LF/HF ratio comparisons between groups were statistically significant at p < 0.05. Conclusions: This study shows that patients with known or suspected orthostatic intolerance and neurodegenerative disorders have reduced HRV, possibly caused by reduced parasympathetic modulation. HRV in patients with known or suspected neurodegenerative disorders is reduced more severely than in patients with orthostatic disorders. Other studies in HRV have indicated a possible increase of risk in cardiovascular disorders in patients with reduced HRV, and therefore, HRV analysis could be a potential clinical diagnostic tool. However, the lack of universally agreed upon methodology, reference values, and possible external and internal factor influence hinders the introduction of HRV examinations into wider clinical practice. Full article

The synthesis and structural characterization of new “2+1” mixed ligand fac-[Re(CO)₃(OO)(L)] and Re(CO)₂(OO)(L)₂ complexes are reported herein. Maltol and kojic acid were chosen as bidentate OO ligands, while imidazole, isocyanocyclohexane or triphenylphosphine were selected as the monodentate ligands. The synthesis of the rhenium complexes was based on the reaction of [NEt₄]₂[Re(CO)₃Br₃] with maltol and kojic acid to generate the intermediate aqua complex fac-[Re(CO)₃(OO)(H₂O)], followed by the replacement of the labile aqua ligand by the monodentate ligand. Structural characterization of all Re complexes was established by NMR and IR spectroscopies, as well as two of them by single-crystal X-ray crystallography, revealing distorted octahedral geometry around the Re center. In the crystal lattice, the complexes form supramolecular networks due to the development of intermolecular interactions of the N-H⋯O, C-H⋯O and C-H⋯π type. Full article

The continuous discharge of organic dyes into freshwater resources poses a long-term hazard to aquatic life. The advanced oxidation Fenton process is a combo of adsorption and degradation of pollutants to detoxify toxic effluents, such as anti-bacterial drugs, antibiotics, and organic dyes. In this work, an activated attapulgite clay-loaded iron-oxide (A-ATP@Fe₃O₄) was produced using a two-step reaction, in which attapulgite serves as an enrichment matrix and Fe₃O₄ functions as the active degrading component. The maximum adsorption capacity (q_t) was determined by assessing the effect of temperature, pH H₂O₂, and adsorbent. The results showed that the A-ATP@Fe₃O₄ achieves the highest removal rate of 99.6% under optimum conditions: 40 °C, pH = 3, H₂O₂ 25 mM, and 0.1 g dosage of the composite. The dye removal procedure achieved adsorption and degradation equilibrium in 120 and 30 min, respectively, by following the same processes as the advanced oxidation approach. Catalytic activity, kinetics, and specified surface characteristics suggest that A-ATP@Fe₃O₄ is one of the most promising candidates for advanced oxidation-enrooted removal of organic dyes. Full article

In order to solve problems such as a slow switching speed, a high switching power, a loss of pure IGBT modulators, and the weak withstanding load short-circuit ability of pure SiC MOSFET modulators used for vacuum loads, this paper proposes a new scheme for high-voltage pulse modulators based on SiC MOSFET/IGBT hybrid connecting circuits. It has a low power loss like the pure SiC MOSFET modulator and a strong withstanding load short-circuit ability like the pure IGBT modulator. Firstly, the principle circuit of the hybrid connecting modulator are discussed and chosen. And the basic working processes of the hybrid parallel-series modulator is described in detail. Secondly, three key points in this new scheme are analyzed and designed as follows: the static and dynamic voltage sharing; the actualizing of the ZVS process for IGBTs; the improvement of short-circuit protection for SiC MOSFETs. A modulator consisting of 16-stage 1200 V-SiC MOSFETs and 1200 V-IGBTs in hybrid parallel-series states is tested. Based on the sample circuit, the working data, such as high-voltage pulse waveforms of 10 kV/2 KHz/10 μs, static and dynamic voltage sharing, the driving control sequence, the U/I sequence of the IGBT, the short-circuit protection waveform, and the calculation, are obtained and discussed. Full article

Background and Objectives: The purpose of the study was to analyze the relationships among several clinical factors and also the tumor topography and surgical strategies used in patients with colorectal cancer. Materials and Methods: We designed an analytical, observational, retrospective study that included patients admitted to our emergency surgical department and diagnosed with colorectal cancer. The study group inclusion criteria were: patients admitted during 2020–2022; patients diagnosed with colorectal cancer (including the ileocecal valve); patients who benefited from a surgical procedure, either emergency or elective. Results: In our study group, consisting of 153 patients, we accounted for 56.9% male patients and 43.1% female patients. The most common clinical manifestations were pain (73.2% of the study group), followed by abdominal distension (69.3% of the study group) and absence of intestinal transit (38.6% of the study group). A total of 69 patients had emergency surgery (45.1%), while 84 patients (54.9%) benefited from elective surgery. The most frequent topography of the tumor was the sigmoid colon, with 19.60% of the patients, followed by the colorectal junction, with 15.68% of the patients, and superior rectum and inferior rectum, with 11.11% of the patients in each subcategory. The most frequent type of procedure was right hemicolectomy (21.6% of the study group), followed by rectosigmoid resection (20.9% of the study group). The surgical procedure was finished by performing an anastomosis in 49% of the patients, and an ostomy in 43.1% of the patients, while for 7.8% of the patients, a tumoral biopsy was performed. Conclusions: Colorectal cancer remains one of the most frequent cancers in the world, with a heavy burden that involves high mortality, alterations in the quality of life of patients and their families, and also the financial costs of the medical systems. Full article

DNA damage checkpoints are essential for coordinating cell cycle arrest and gene transcription during DNA damage response. Exploring the targets of checkpoint kinases in Saccharomyces cerevisiae and other fungi has expanded our comprehension of the downstream pathways involved in DNA damage response. While the function of checkpoint kinases, specifically Rad53, is well documented in the fungal pathogen Candida albicans, their targets remain poorly understood. In this study, we explored the impact of deleting RAD53 on the global transcription profiles and observed alterations in genes associated with ribosome biogenesis, DNA replication, and cell cycle. However, the deletion of RAD53 only affected a limited number of known DNA damage-responsive genes, including MRV6 and HMX1. Unlike S. cerevisiae, the downregulation of HOF1 transcription in C. albicans under the influence of Methyl Methanesulfonate (MMS) did not depend on Dun1 but still relied on Rad53 and Rad9. In addition, the transcription factor Mcm1 was identified as a regulator of HOF1 transcription, with evidence of dynamic binding to its promoter region; however, this dynamic binding was interrupted following the deletion of RAD53. Furthermore, Rad53 was observed to directly interact with the promoter region of HOF1, thus suggesting a potential role in governing its transcription. Overall, checkpoints regulate global gene transcription in C. albicans and show species-specific regulation on HOF1; these discoveries improve our understanding of the signaling pathway related to checkpoints in this pathogen. Full article

Zeolites of natural origin are materials exhibiting many positive effects on the human body. Silver-modified zeolites have already been introduced as bactericidal agents, although studies dealing with their toxicity are insufficient. This work describes the synthesis of activated and silver-loaded Bulgarian zeolite using a simple wet impregnation method. Morphological characteristics and compositions of natural zeolite, activated zeolite, and Ag-nanocomposites were studied by the X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM) methods. Silver loading is approximately 13 wt. %, with mean Ag particle size around 19 nm. Analyses of the samples included antioxidant activity assays based on ABTS radical scavenging ability and in vitro cytotoxicity tests with human normal fibroblasts and three adenocarcinoma cell lines. The experiments were performed with natural, activated, and Ag-modified zeolite in comparison to two commercial food supplements. Our results indicated moderate antioxidant activity of the tested samples. Silver-modified zeolite demonstrated cytotoxic effects against both tumor cells and normal fibroblasts, but the detected levels of inhibition were stronger against the adenocarcinoma cells, suggesting anti-tumor potential. The present article indicates a new aspect of Bulgarian natural zeolite and Ag-loaded zeolite biological activity. It highlights the need for detailed toxicity evaluations of Ag-nanocomposites prior to healthcare applications. Full article

Background: Food insecurity is a heightened concern among economically disadvantaged youth, and it may contribute to the atypical body mass index (BMI) patterns frequently observed in this group. Self-efficacy seems to intervene in the negative impacts of contextual restraints. This study investigated the relationship between food insecurity, self-efficacy, and BMI trajectory among economically disadvantaged Taiwanese youth. Methods: We utilized three-wave longitudinal data from the Taiwan Database of Children and Youth in Poverty. The Food Insecurity Score (FIS) assessed food insecurity with a 4-item scale measuring reduced meal frequency, hunger, skipping meals, and economic constraints. Moreover, the General Self-Efficacy Scale (GSES) assessed self-efficacy, showcasing the ability to handle stress effectively and envision success scenarios, contributing to positive outcomes. By employing latent growth modeling, we were able to delineate the impacts of baseline food insecurity and self-efficacy on initial BMI and its subsequent growth trajectory. Results: Elevated baseline FIS significantly predicted higher initial BMI (coefficient = 0.420, p = 0.042). Baseline GSES was negatively associated with initial BMI (coefficient = −0.093, p < 0.001) but positively predicted the BMI growth rate (coefficient = 0.023, p = 0.011). Conclusion: Enhancing self-efficacy may be an effective multidisciplinary intervention to address psychosocial and socioeconomic factors when tackling weight problems in vulnerable youth groups. Full article

Adipose-derived stem cells (ADSCs) are mesenchymal stem cells with a great potential for self-renewal and differentiation. Exosomes derived from ADSCs (ADSC-exos) can imitate their functions, carrying cargoes of bioactive molecules that may affect specific cellular targets and signaling processes. Recent evidence has shown that ADSC-exos can mediate tissue regeneration through the regulation of the inflammatory response, enhancement of cell proliferation, and induction of angiogenesis. At the same time, they may promote wound healing as well as the remodeling of the extracellular matrix. In combination with scaffolds, they present the future of cell-free therapies and promising adjuncts to reconstructive surgery with diverse tissue-specific functions and minimal adverse effects. In this review, we address the main characteristics and functional properties of ADSC-exos in tissue regeneration and explore their most recent clinical application in wound healing, musculoskeletal regeneration, dermatology, and plastic surgery as well as in tissue engineering. Full article

Methyltransferases are a wide-ranging, yet well-conserved, class of molecules that have been found to modify a wide variety of substrates. Interest in RNA methylation has surged in recent years with the identification of the major eukaryotic mRNA m6A methyltransferase METTL3. METTL16 has also been identified as an RNA m6A methyltransferase; however, much less is known about its targets and actions. Interestingly, in addition to their catalytic activities, both METTL3 and METTL16 also have “methylation-independent” functions, including translational regulation, which have been discovered. However, evidence suggests that METTL16’s role as an RNA-binding protein may be more significant than is currently recognized. In this review, we will introduce RNA methylation, specifically m6A, and the enzymes responsible for its deposition. We will discuss the varying roles that these enzymes perform and delve deeper into their RNA targets and possible roles as methylation-independent RNA binding proteins. Finally, we will touch upon the many open questions still remaining. Full article

Alkaline seawater electrolysis has garnered significant attention as an efficient, green, and sustainable method for producing green hydrogen in recent years. However, the lack of highly active anodes in seawater electrolysis to prevent chloride oxidation reactions has limited its commercial application. In this study, Au single atoms were deposited on NiCoFeS through the electrochemical deposition method. The optimized catalyst exhibited significantly enhanced activity in seawater electrolyte; the Au@NiCoFeS catalyst achieved a current density of 10 mA/cm² with only 183 mV and maintained its performance without degradation for 250 h at a current density of 200 mA/cm², with no corrosion observed on either the catalyst or the substrate. Full article

This research focuses on the target deconvolution of the natural compound myrianthic acid, a triterpenoid characterized by an ursane skeleton isolated from the roots of Myrianthus arboreus and from Oenothera maritima Nutt. (Onagraceae), using MS-based chemical proteomic techniques. Application of drug affinity responsive target stability (DARTS) and targeted-limited proteolysis coupled to mass spectrometry (t-LiP-MS) led to the identification of the enzyme fatty acid synthase (FAS) as an interesting macromolecular counterpart of myrianthic acid. This result, confirmed by comparison with the natural ursolic acid, was thoroughly investigated and validated in silico by molecular docking, which gave a precise picture of the interactions in the MA/FAS complex. Moreover, biological assays showcased the inhibitory activity of myrianthic acid against the FAS enzyme, most likely related to its antiproliferative activity towards tumor cells. Given the significance of FAS in specific pathologies, especially cancer, the myrianthic acid structural moieties could serve as a promising reference point to start the potential development of innovative approaches in therapy. Full article

Background and Objective: This study aimed to identify the incidence of sarcopenia and disease risk factors in Korean adults and to provide data for sarcopenia prevention. Materials and Methods: Based on the Korea National Health and Nutrition Survey, 2008–2011, we selected 14,185 adults over the age of 20 who participated in sarcopenia diagnostic tests and health surveys. We analyzed sarcopenia risk factors using complex sample multi-logistic regression analysis. Results: The prevalence of sarcopenia in Korea was 31.3%, with 20.2% in men and 40.4% in women. In men, there was a higher risk of sarcopenia in those of older age, without a spouse, with a low body mass index (BMI), who never engage in resistance exercise, or who do mid-level intensity resistance exercises. In women, sarcopenia risk was higher in those in their 20s compared to those in their 60s, and risk factors included a low BMI, high-density lipoprotein cholesterol and waist circumference measurements, alcohol consumption, aerobic exercise, and resistance exercise. Conclusions: Interventions and lifestyle improvements will help prevent the onset of sarcopenia in elderly men and young women with risk factors such as a low BMI. Full article

Key aspects of communities of the Internet of Things (IoT) smart objects presenting social aspects are represented by trust and reputation relationships between the objects. Several trustworthiness models have been presented in the literature in the context of multi-smart object community that could be adopted in the IoT scenario; however, most of these approaches represent the different dimensions of trust using scalar measures, then integrating these measures in a global trustworthiness value. In this paper, we discuss the limitation of this approach in the IoT context, highlighting the necessity of modeling complex trust relationships that cannot be captured by a vector-based model, and we propose a new trust model in which the trust perceived by an object with respect to another object is modeled by a directed, weighted graph whose vertices are trust dimensions and whose arcs represent relationships between trust dimensions. By using this new model, we provide the IoT community with the possibility of representing also situations in which an object does not know a trust dimension, e.g., reliability, but it is able to derive it from another one, e.g., honesty. The introduced model can represent any trust structure of the type illustrated above, in which several trust dimensions are mutually dependent. Full article

The fourth industrial revolution has transformed the industry, with information technology playing a crucial role in this shift. The increasing digitization of industrial systems demands efficient sensing and control methods, giving rise to soft sensors that have the potential to replace traditional physical sensors in order to reduce costs and enhance efficiency. This study explores the implementation of an artificial neural network (ANN) based soft sensor model in a water supply system to predict flow rates within the system. The soft sensor is centered on a Long Short-Term Memory (LSTM) artificial neural network model using Monte Carlo dropout to reduce uncertainty and improve estimation performance. Based on the results of this work, it is concluded that the proposed soft sensor (with Monte Carlo dropout) can predict flow rates more precisely, contributing to the reduction in water losses, as well as cost savings. This approach offers a valuable solution for minimizing water losses and ensuring the efficient use of this vital resource. Regarding the use of soft sensors based on LSTM neural networks with a careful choice of Monte Carlo dropout parameters, when compared to the multilayer perceptron model, the LSTM model with Monte Carlo dropout showed better mean absolute error, root mean square error, and coefficient of determination: 0.2450, 0.3121, and 0.996437 versus 0.2556, 0.3522, and 0.9954. Furthermore, this choice of Monte Carlo dropout parameters allowed us to achieve an LSTM network model capable of reducing uncertainty to 1.8290, keeping the error metrics also at low levels. Full article

Polymers have become an important part of everyday life, but most of the polymers currently used are petroleum-based. This poses an environmental problem, especially with respect to products that are quickly discarded. For this reason, current packaging development focuses on sustainable materials as an alternative to synthetic ones. Nanocellulose, a relatively new material derived from cellulose, has unique properties such as high strength, low density, high surface area, and good barrier properties, making it popular in various applications. Additionally, 3D printing technologies have become an important part of industrial and commercial processes, enabling the realization of innovative ideas and functionalities. The main aim of this research was to develop a hydrogel of bacterial nanocellulose with suitable rheological properties for the 3D printing of polymer foils. Three variations of bacterial nanocellulose hydrogel differing in ratios of bacterial nanocellulose to cationic starch were produced. The rheological studies confirmed the suitability of the hydrogels for 3D printing. Foils were successfully 3D-printed using a modified 3D printer. The physical-mechanical, surface, and optical properties of the foils were determined. All foils were homogeneous with adequate mechanical properties. The 3D-printed foils with the highest amount of cationic starch were the most homogeneous and transparent and, despite their rigidity, very strong. All foils were semi-transparent, had a non-glossy surface, and retained poor water wettability. Full article

The aging population and increasing incidence of trauma among younger age groups have heightened the increasing demand for reliable implant materials. Effective implant materials must demonstrate rapid osseointegration and strong antibacterial properties to ensure optimal patient outcomes and decrease the chance of implant rejection. This study aims to enhance the bone–implant interface by utilizing 45S5 bioglass modified with various concentrations of Fe₃O₄ as a coating material. The effect of the insertion of Fe₃O₄ into the bioglass structure was studied using Raman spectroscopy which shows that with the increase in Fe₃O₄ concentration, new vibration bands associated with Fe-related structural units appeared within the sample. The bioactivity of the prepared glasses was evaluated using immersion tests in simulated body fluid, revealing the formation of a calcium phosphate-rich layer within 24 h on the samples, indicating their potential for enhanced tissue integration. However, the sample modified with 8 mol% of Fe₃O₄ showed low reactivity, developing a calcium phosphate-rich layer within 96 h. All the bioglasses showed antibacterial activity against the Gram-positive and Gram-negative bacteria. The modified bioglass did not present significant antibacterial properties compared to the bioglass base. Full article

Sustainable rural development forms a robust foundation for economic and social sustainability. Moreover, the digital economy acts as a catalyst for advancing rural sustainable development by altering the distribution of production factors. Thus, this study concentrates on 30 provinces in China, constructing an evaluation index system for both the digital economy and rural sustainable development. The study employs various methods and models to analyze the spatiotemporal changes and driving factors affecting the coupling and coordination between these two aspects. The research findings are as follows: the coupling and coordination levels among provinces in China have been on the rise year by year. By 2022, the coupling and coordination levels of most provinces range between 0.5 and 0.6. Regional disparities are the primary determinant of the poor overall coupling and coordination level in China. In 2022, the coupling and coordination level in the eastern region is 0.6663, compared to 0.5420 in the central region and 0.5087 in the western region. Factors such as urbanization, industrial structure transformation, technological innovation, higher education, economic development, and government support significantly influence the coupling and coordination level. Nevertheless, their effects vary across regions, with a more pronounced impact in the eastern region than in the central and western regions. Therefore, this paper proposes policy recommendations, including infrastructure optimization, rural digitization promotion, regional resource allocation enhancement, cross-regional development mechanism exploration, and differentiated development strategy implementation. Full article

The compound classification strategies addressed in this study encounter challenges related to either low efficiency or accuracy. Precise classification of chemical compounds from SMILES symbols holds significant importance in domains such as drug discovery, materials science, and environmental toxicology. In this paper, we introduce a novel hybrid optimization framework named GA-CMA-ES which integrates Genetic Algorithms (GA) and the Covariance Matrix Adaptation Evolution Strategy (CMA-ES) to train Recurrent Neural Networks (RNNs) for compound classification. Leveraging the global exploration capabilities og GAs and local exploration abilities of the CMA-ES, the proposed method achieves notable performance, attaining an 83% classification accuracy on a benchmark dataset, surpassing the baseline method. Furthermore, the hybrid approach exhibits enhanced convergence speed, computational efficiency, and robustness across diverse datasets and levels of complexity. Full article

Experiments conducted on triple-negative breast cancer have shown that fucoidan from Lessonia trabeculata (FLt) exhibits cytotoxic and antitumor properties. However, further research is necessary to gain a complete understanding of its bioactivity and level of cytotoxicity. The cytotoxic effect of FLt was determined by the 2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Apoptosis was analyzed using annexin V and caspase 3/7 staining kit and DNA fragmentation. In addition, transcriptional expression of antiapoptotic (Bcl-2 and XIAP) and proapoptotic (caspase 8, caspase 9, and AIF) genes were analyzed in TNBC 4T1 cells. After 72 h of culture, the IC₅₀ for FLt was 561 μg/mL, while doxorubicin (Dox) had an IC₅₀ of 0.04 μg/mL. In addition, assays for FLt + Dox were performed. Annexin V and caspase 3/7 revealed that FLt induces early and late-stage apoptosis. DNA fragmentation results support necrotic death of 4T1 cells. Similarly, transcripts that prevent cell death were decreased, while transcripts that promote cell death were increased. This study showed that FLt induces apoptosis by both caspase-dependent and caspase-independent mechanisms. These findings suggest that FLt may have potential applications in breast cancer treatment. Further research will provide more information to elucidate the mechanism of action of FLt. Full article

Dysregulation of the insulin-like growth factor (IGF) system determines the onset of various pathological conditions, including cancer. Accordingly, therapeutic strategies have been developed to block this system in tumor cells, but the results of clinical trials have been disappointing. After decades of research in the field, it is safe to say that one of the major reasons underlying the poor efficacy of anti-IGF-targeting agents is derived from an underestimation of the molecular complexity of this axis. Genetic, transcriptional, post-transcriptional and functional interactors interfere with the activity of canonical components of this axis, supporting the need for combinatorial approaches to effectively block this system. In addition, cancer cells interface with a multiplicity of factors from the extracellular compartment, which strongly affect cell destiny. In this review, we will cover novel extracellular mechanisms contributing to IGF system dysregulation and the implications of such dangerous liaisons for cancer hallmarks and responses to known and new anti-IGF drugs. A deeper understanding of both the intracellular and extracellular microenvironments might provide new impetus to better decipher the complexity of the IGF axis in cancer and provide new clues for designing novel therapeutic approaches. Full article