Search Results (77)

Background/Objectives: Doxorubicin (DOX), a widely used anthracycline chemotherapeutic agent, is recognized for its efficacy in treating various malignancies. However, its clinical application is critically limited due to dose-dependent cardiotoxicity, predominantly induced by oxidative stress and compromised antioxidant defenses. Photobiomodulation (PBM), a non-invasive intervention that utilizes low-intensity light, has emerged as a promising therapeutic modality in regenerative medicine, demonstrating benefits such as enhanced tissue repair, reduced inflammation, and protection against oxidative damage. This investigation sought to evaluate the cardioprotective effects of PBM preconditioning in human-induced pluripotent stem cell-derived ventricular cardiomyocytes (hiPSC-vCMs) subjected to DOX-induced toxicity. Methods: Human iPSC-vCMs were allocated into three experimental groups: control cells (untreated), DOX-treated cells (exposed to 2 μM DOX for 24 h), and PBM+DOX-treated cells (preconditioned with PBM, utilizing 660 nm ±10 nm LED light at an intensity of 10 mW/cm² for 500 s, delivering an energy dose of 5 J/cm², followed by DOX exposure). Cell viability assessments were conducted in conjunction with evaluations of oxidative stress markers, including antioxidant enzyme activities and malondialdehyde (MDA) levels. Furthermore, transcriptional profiling of 40 genes implicated in cardiac dysfunction was performed using TaqMan quantitative polymerase chain reaction (qPCR), complemented by analyses of protein expression for markers of cardiac stress, inflammation, and apoptosis. Results: Exposure to DOX markedly reduced the viability of hiPSC-vCMs. The cells exhibited significant alterations in the expression of 32 out of 40 genes (80%) after DOX exposure, reflecting the upregulation of markers associated with apoptosis, inflammation, and adverse cardiac remodeling. PBM preconditioning partially restored the cell viability, modulating the expression of 20 genes (50%), effectively counteracting a substantial proportion of the dysregulation induced by DOX. Notably, PBM enhanced the expression of genes responsible for antioxidant defense, augmented antioxidant enzyme activity, and reduced oxidative stress indicators such as MDA levels. Additional benefits included downregulating stress-related mRNA markers (HSP1A1 and TNC) and apoptotic markers (BAX and TP53). PBM also demonstrated gene reprogramming effects in ventricular cells, encompassing regulatory changes in NPPA, NPPB, and MYH6. PBM reduced the protein expression levels of IL-6, TNF, and apoptotic markers in alignment with their corresponding mRNA expression profiles. Notably, PBM preconditioning showed a diminished expression of BNP, emphasizing its positive impact on mitigating cardiac stress. Conclusions: This study demonstrates that PBM preconditioning is an effective strategy for reducing DOX-induced chemotherapy-related cardiotoxicity by enhancing cell viability and modulating signaling pathways associated with oxidative stress, as well as inflammatory and hypertrophic markers. Full article

Colorectal cancer (CRC) is a multifactorial disease increasingly recognized for its complex interplay with the gut microbiota. The disruption of microbial homeostasis—dysbiosis—has profound implications for intestinal barrier integrity and host immune function. Pathogenic bacterial species such as Fusobacterium nucleatum, Escherichia coli harboring polyketide synthase (pks) island, and enterotoxigenic Bacteroides fragilis are implicated in CRC through mechanisms involving mucosal inflammation, epithelial barrier disruption, and immune evasion. These pathogens promote pro-tumorigenic inflammation, enhance DNA damage, and suppress effective anti-tumor immunity. Conversely, commensal and probiotic bacteria, notably Lactobacillus and Bifidobacterium species, exert protective effects by preserving epithelial barrier function and priming host immune responses. These beneficial microbes can promote the maturation of dendritic cells, stimulate CD8⁺ T cell cytotoxicity, and modulate regulatory T cell populations, thereby enhancing anti-tumor immunity. The dichotomous role of the microbiota underscores its potential as both a biomarker and a therapeutic target in CRC. Recent advances in studies have explored microbiota-modulating strategies—ranging from dietary interventions and prebiotics to fecal microbiota transplantation (FMT) and microbial consortia—as adjuncts to conventional therapies. Moreover, the composition of the gut microbiome has been shown to influence the responses to immunotherapy and chemotherapy, raising the possibility of microbiome-informed precision oncology therapy. This review synthesizes the current findings on the pathogenic and protective roles of bacteria in CRC and evaluates the translational potential of microbiome-based interventions in shaping future therapeutic paradigms. Full article

Magnesium (Mg²⁺) has gained oncologists’ attention due to its wide range of biological functions and frequent use as a complementary or integrative agent. This review outlines Mg’s actions, its complex role in carcinogenesis and tumor risk, and clinical issues. Mg²⁺ is essential in numerous biochemical processes, including adenosine triphosphate production, cellular signal transduction, DNA, RNA and protein synthesis, and bone formation. Pertinent full-text articles were thoroughly examined, and the most relevant ones were selected for inclusion in this review. There is conflicting scientific evidence about the relationship between Mg²⁺ changes and cancer risk, apart from colorectal cancer. Chronic Mg²⁺ deficiency leads to immune dysfunctions and enhanced baseline inflammation associated with oxidative stress related to various age-associated morbidities and cancer. On the other hand, Mg²⁺ deficiency is associated with drug or chemotherapy-related hypomagnesemia, postoperative pain, cachexia, opioid-induced constipation, normal tissue protection from radiation damage, and prevention of nephrotoxicity. A balanced diet usually provides sufficient Mg²⁺, but supplementation may be necessary in some clinical settings. Full article

Triple-negative breast cancer (TNBC), characterized by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), remains a therapeutic challenge due to its aggressive nature, limited treatment options, and high recurrence rates. Current therapies, including chemotherapy and immune checkpoint inhibitors, face resistance driven by tumor heterogeneity, immunosuppressive signaling, and dysregulated redox pathways. This review explores silibinin’s potential to modulate the tumor immune microenvironment (TIME) and overcome therapeutic resistance in TNBC. Silibinin exerts multifaceted anticancer effects by suppressing PD-L1 expression through the inhibition of JAK/STAT3 signaling and MUC1-C interaction, attenuating NF-κB-driven inflammation, and downregulating CCL2-mediated recruitment of tumor-associated macrophages (TAMs). Additionally, silibinin disrupts redox adaptation by targeting the Nrf2-EGFR-MYC-TXNIP axis, enhancing oxidative stress and chemosensitivity. Preclinical studies highlight its ability to inhibit epithelial–mesenchymal transition (EMT), reduce cancer stem cell (CSC) populations, and synergize with existing therapies like PD-1 inhibitors. Despite its low bioavailability, advanced formulations such as liposomes and nanoparticles show promise in improving delivery and efficacy. By reshaping TIME through dual antioxidant and immunomodulatory mechanisms, silibinin emerges as a viable adjunct therapy to reverse immunosuppression and chemoresistance in TNBC. Full article

The sustainable use of agri-food by-products offers a significant opportunity. Increasing evidence shows that these by-products have various bioactive compounds that help reduce inflammation and, in turn, the severity of several proliferative diseases. Numerous epidemiological studies have suggested an inverse relationship between the consumption of fruits and vegetables and the incidence of breast cancer. Anti-breast cancer effects involve a variety of mechanisms, inhibiting proliferation, migration, metastasis, and angiogenesis of breast tumor cells; inducing apoptosis and cell cycle arrest; and enhancing the sensitivity of breast tumor cells to radiotherapy and chemotherapy. Extensive research suggests that the Mediterranean diet has various bioactive compounds known to provide protective effects against a wide range of non-communicable diseases. Among the phytochemicals identified as protective against breast cancer, natural polyphenols have shown antioxidant, anti-inflammatory, immunomodulatory, and anticancer properties. This review highlights the potential role of natural dietary products and their primary bioactive components in preventing and treating breast cancer, with special emphasis on the mechanisms of action. The integration of agri-food by-products into the diet not only offers opportunities for the prevention and treatment of breast cancer but also promotes sustainable use of resources, contributing to the reduction of waste and the improvement of global health. Full article

Background: Granulomatous and amyloidogenic cardiomyopathies are infiltrative conditions that can be fatal if left untreated. Among these, cardiac amyloidosis and cardiac sarcoidosis are significant but often underdiagnosed causes of heart failure, each serving as cardiac manifestations of broader systemic diseases. Advancements in imaging techniques and the emergence of novel therapies—particularly for cardiac amyloidosis—have brought these conditions into sharper focus for both clinicians and researchers. Methods: We conducted a comprehensive review of the literature by searching databases including PubMed and Scopus for studies published since 1990 regarding clinical features, diagnostic techniques, and treatment strategies for cardiac amyloidosis and cardiac sarcoidosis. Studies were selected based on relevance to imaging methods, including echocardiography, cardiac magnetic resonance imaging (CMR), positron emission tomography (PET), and technetium-labeled nuclear scintigraphy, as well as treatment modalities for both conditions. Results: Imaging techniques, particularly CMR, technetium-labeled nuclear scan, and PET, were found to be crucial for the early identification and differentiation of cardiac amyloidosis and cardiac sarcoidosis. Distinct late gadolinium enhancement patterns were observed in CMR along with morphological differences, aiding in diagnosis. Technetium-labeled nuclear scintigraphy can definitively distinguish between subtypes of cardiac amyloidosis in the absence of paraproteinemia. Early diagnosis has been shown to significantly improve patient outcomes. Early treatment can reduce morbidity in both cardiomyopathies. Conclusions: Multimodality imaging can help in the early detection of cardiac amyloidosis and cardiac sarcoidosis. Treatment strategies differ substantially: cardiac amyloidosis is primarily managed with disease-modifying therapies for the transthyretin subtype and chemotherapy/stem cell transplant for the AL subtype, while cardiac sarcoidosis is treated with corticosteroids and immunosuppressive drugs to reduce inflammation. Early and accurate diagnosis through advanced imaging techniques is critical to improving outcomes for patients with these conditions. Full article

Background: Gastric cancer (GC) is a highly aggressive disease often complicated by resistance to chemotherapy agents like paclitaxel (PTX), which targets microtubules to induce apoptosis. Resistance arises through complex molecular mechanisms, including the overexpression of pro-angiogenic factors (VEGFA, ANG-2), activation of survival pathways (PDGFRβ, PPARγ), and epithelial-mesenchymal transition (EMT) driven by proteins such as VIM, E-CAD, N-CAD, and FLOT-1. The extracellular matrix (ECM), regulated by COL1A1 and influenced by PPARγ, acts as a physical barrier to drug penetration. Small extracellular vesicles (sEVs) have emerged as critical mediators of intercellular communication and may influence these resistance pathways. Methods: This study investigated the role of sEVs isolated from metastatic GC patients treated with Ramucirumab and PTX. Patients were stratified by progression-free survival (PFS) into rapidly progressing (RP) and controlled disease (CD) groups. sEVs from these patients were applied to HCEC-1CT and HEPA-RG cell lines. Cell viability assays, gene and protein expression analyses, and bioinformatic studies were conducted to assess the impact of sEVs on resistance-related markers. Results: Results showed that sEVs from CD patients reduced the expression of markers associated with drug resistance, while sEVs from RP patients increased these markers, promoting angiogenesis, EMT, and ECM remodeling. These changes correlated with enhanced cell survival and resistance phenotypes. Bioinformatic analyses confirmed that sEVs modulate inflammation, ECM dynamics, and EMT pathways. Conclusions: In conclusion, sEVs from metastatic GC patients significantly influence chemoresistance and tumor progression. Targeting sEV-mediated signaling may offer novel therapeutic strategies to overcome resistance and improve treatment outcomes in gastric cancer. Full article

Background/Objectives: The low permeability of the blood-brain barrier (BBB) represents a significant challenge to effective systemic chemotherapy for primary and metastatic brain cancers. Kinin receptors play a crucial role in modulating BBB permeability, and their agonist analogs have been explored in preclinical animal models to enhance drug delivery to the brain. In this study, we investigated whether des-Arg⁹-bradykinin (DBK), a physiological agonist of kinin B₁ receptor (B1R), acts as a brain drug delivery adjuvant by promoting the transient opening of the BBB. Methods: Human brain microvascular endothelial cells (HBMECs) were treated with DBK in the culture medium and in conditioned media from glioblastoma cell lines, namely T98G (CMT98G) and U87MG (CMU87). Immunofluorescence, RT-qPCR, in-cell Western assay, and proximity ligation assay (PLA) were performed to analyze BBB components, kinin receptors and TLR4, a receptor associated with the kinin pathway and inflammation. The effect of DBK on enhancing paracellular molecule transport was evaluated using Evans blue dye (EB) quantification in a cell culture insert assay and in an in vivo model, where mice with and without brain tumors were treated with DBK. To assess the functional impact of the transient BBB opening induced by DBK, the chemotherapeutic drug doxorubicin (DOX) was administered. Results: Treatment with DBK facilitates the presence of EB in the brain parenchyma by transiently disrupting the BBB, as further evidenced by the increased paracellular passage of the dye in an in vitro assay. B1R activation by DBK induces transient BBB opening lasting less than 48 h, enhancing the bioavailability of the DOX within the brain parenchyma and glioma tumor mass. The interaction between B1R and TLR4 is disrupted by the secreted factors released by glioblastoma cells, as conditioned media from T98G and U87 reduce TLR4 staining in endothelial cells without affecting B1R expression. Conclusions: These results further support the potential of B1R activation as a strategy to enhance targeted drug delivery to the brain. Full article

Estrogen receptors (ERs) play a critical role in breast cancer (BC) development and progression, with ERα being oncogenic and ERβ exhibiting tumor-suppressive properties. The interaction between ER signaling and other molecular pathways, such as PI3K/AKT/mTOR, influences tumor growth and endocrine resistance. Emerging research highlights the role of prebiotics in modulating gut microbiota, which may influence estrogen metabolism, immune function, and therapeutic responses in BC. This review explores the impact of prebiotics on estrogen receptor modulation, gut microbiota composition, immune regulation, and metabolic pathways in breast cancer. The potential of prebiotics as adjunctive therapies to enhance treatment efficacy and mitigate chemotherapy-related side effects is discussed. A comprehensive analysis of recent preclinical and clinical studies was conducted, examining the role of prebiotics in gut microbiota modulation, immune regulation, and metabolic reprogramming in breast cancer. The impact of short-chain fatty acids (SCFAs) derived from prebiotic fermentation on epigenetic regulation and endocrine resistance was also evaluated. Prebiotics were found to modulate the gut microbiota-estrogen axis, reduce inflammation, and influence immune responses. SCFAs demonstrated selective estrogen receptor downregulation and metabolic reprogramming, suppressing tumor growth. Synbiotic interventions mitigate chemotherapy-related side effects, improving the quality of life in breast cancer patients. Prebiotics offer a promising avenue for breast cancer prevention and therapy by modulating estrogen metabolism, immune function, and metabolic pathways. Future clinical trials are needed to validate their efficacy as adjunctive treatments in breast cancer management. Full article

Radiation is often used as the primary treatment for a range of cancers. Nonetheless, its ability to trigger secondary tumors has emerged as a significant issue. Therefore, gaining insight into and predicting radiation-induced secondary cancers is essential for enhancing the long-term prognosis of cancer survivors. Background and Objectives: Previous studies have identified several factors; however, research on the use of serum-based inflammatory markers as prognostic tools for predicting radiation-induced secondary malignancies is limited. Investigating the potential of serum-based inflammation prognostic scores could provide a minimally invasive and affordable method for the early prediction of secondary malignancies. Methods: We retrospectively analyzed a patient cohort with radiation-induced secondary malignancy from the electronic database MIMIC-IV to investigate whether a serum-based inflammatory marker score can serve as a predictive tool. Results: This study seeks not only to assess the efficacy of the risk score, but also to develop a clinical utility tool nomogram for predicting the occurrence of radiation-induced secondary cancers. A RISM of 4.28% was observed in a cohort from the MIMIC-IV database using SIRI-RT as a risk index, with the Charlson comorbidity index, chemotherapy, and creatinine levels as significant confounding risk factors. Conclusions: Our study suggests that elevated serum-based inflammation prognostic scores and the nomogram developed herein can be used to predict a greater likelihood of developing secondary malignancies following radiation therapy. Full article

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a rising global health issue. Chronic intestinal inflammation is an important risk factor for colorectal cancer (CRC). Despite significant progress in IBD and CRC treatment, numerous patients remain resistant to standard pharmacotherapy or experience severe side effects that prevent them from continuing treatment. There is evidence suggesting that bioactive substances in Lentinula edodes have immunomodulatory and anticancer properties. This fungus is currently classified as a functional food, considering its beneficial effects on human health and special nutritional value. Studies conducted in vitro and in animal models demonstrated that L. edodes bioactive compounds, in particular glucans, have anti-inflammatory and antioxidant effects, induce apoptosis of cancer cells, reduce tumor angiogenesis, restore gut microbiome heterogeneity and improve gut barrier dysfunction. Moreover, clinical trials confirmed that these compounds combined with standard chemotherapy have a significant effect in improving the prognosis of CRC patients. In addition, L. edodes glucans increase microbial diversity and enhance interferon (IFN)-γ production by immune cells. Future studies must be focused on understanding the pathways and mechanisms associated with the observed effects. Moreover, both randomized trials and long-term follow-up studies are needed to confirm their effectiveness in the treatment of IBD and CRC. Full article

Glioblastoma (GBM) remains the most aggressive primary brain tumor, with poor survival outcomes and treatment limited to maximal safe surgical resection, chemotherapy with temozolomide, and radiotherapy. While immunotherapy and targeted treatments show promise, therapeutic resistance and disease progression remain major challenges. This is partly due to GBM’s classification as a “cold tumor” with low mutational burden and a lack of distinct molecular targets for drug delivery that selectively spare healthy tissue. Emerging evidence highlights the gut microbiota as a key player in cancer biology, influencing both glioma development and treatment response. This review explores the intersectionality between the gut microbiome and GBM, beginning with an overview of microbiota composition and its broader implications in cancer pathophysiology. We then examine how specific microbial populations contribute to glioma oncogenesis, modulating immune responses, inflammation, and metabolic pathways that drive tumor initiation and progression. Additionally, we discuss the gut microbiome’s role in glioma therapeutic resistance, including its impact on chemotherapy, radiotherapy, and immunotherapy efficacy. Given its influence on treatment outcomes, we evaluate emerging strategies to modulate gut flora, such as probiotics, dietary interventions, and microbiota-based therapeutics, to enhance therapy response in GBM patients. Finally, we address key challenges and future directions, emphasizing the need for standardized methodologies, mechanistic studies, and clinical trials to validate microbiota-targeted interventions in neuro-oncology. By integrating gut microbiome research into GBM treatment paradigms, we may unlock novel therapeutic avenues to improve patient survival and outcomes. Full article

In-hospital patients who are in the gynecologic oncology setting often suffer from malnutrition, which is one of the primary problems, the rate of which reportedly ranges from 28% to 70%. Malnutrition is a significant risk factor for immunosuppression, negatively impacting immune response and postoperative recovery capacity. At the time of the surgeries, due to their wide scope and aggressive treatments such as chemotherapy and radiotherapy, the situation becomes more serious. Those micronutrients taking part in immunonutrition, namely, arginine, omega-3 fatty acids, nucleotides, and antioxidants, have the potential to prevent inflammation, protect against infections, and promote healing after the surgery. Research has shown that immunonutrition can lower the risk of postoperative infection, promote the normal healing of wounds, and reduce the hospital stays of patients, as well as support malnutrition status during chemotherapy. This review is based on a literature search conducted in Medline, Scopus, Clinicaltrials.gov, Cochrane CENTRAL, and Google Scholar, with the last search date being November 2024. Some studies. found that perioperative immunonutrition decreases wound infections and affects some immune indexes in gynecologic oncology patients positively. However, factors such as non-compliant patients, high costs, and non-standard formulations can deter its wider use. Patient adherence drops postoperatively mainly due to nausea and decreased appetite, whereas the cost of enriched formulations acts as an economic barrier. Postoperative compliance drops from ~78% prior to surgery to ~28% due to nausea, anorexia, and chemotherapy. Additionally, cost remains a constraining factor since special formulas are 2–4 times that of normal nutrition. While immunonutrition reduces hospital stay (by ~2–3 days) and infection rate (by 25–40%), access is hindered by prohibitive initial costs and lack of insurance coverage. Approaches such as subsidized schemes, enhanced palatability, and cost–benefit analyses are required to increase adoption. In addition, the lack of standardized protocols makes the clinical community hesitant to adopt this approach. Immunonutrition is, despite these problems, still hoped to be the new adjunct to gynecologic oncology patients. In future studies, it is imperative to pay attention to the best formulations that produce the best outcomes and evaluate and implement guidelines that are based on evidence. Together, with these improvements, immunonutrition could very well be an integral part of perioperative care thus completing the process by which patients in intense treatments are benefited not only via treatment but also via quality of life. Full article

Background and Objectives: Despite the development of treatment methods and the emergence of alternative new approaches in recent years, the visual prognosis of retinoblastoma contains deficiencies and this situation increases the need for the development of new treatment approaches. The cytotoxic and apoptosis-inducing effects of the combination of boswellic acid (BA), which has been determined to have significant potential in preclinical and clinical studies of various diseases, and Cisplatin (Cis), a potent chemotherapy agent, were investigated on the human retinoblastoma cell line (Y79). Materials and Methods: The cytotoxic effect of BA and Cis on Y79 cells was determined by the water soluble tetrazolium-1 (WST-1) test, the apoptotic rate of the cells was determined by annexin V staining, and the gene expressions of Protein53 (p53), Caspase-3 and Nuclear factor kappa B (NF-κB), which play an important role in apoptosis, were determined by RT-qPCR analysis. Interleukin 1-beta (IL1-β), tumor necrosis factor-α (TNF-α) and interferon γ (IFN-γ) levels were analyzed in cell lysates obtained from the experimental groups. Results: The combination of BA and Cis selectively inhibited the growth of Y79 cells and modulated NF-κB signaling, potentially through post-translational regulatory mechanisms. Moreover, it induced apoptosis by increasing p53 and Caspase-3 expressions, confirming its pro-apoptotic effects. Additionally, the combination treatment was associated with a reduction in inflammatory cytokine levels (TNF-α, IL1-β), suggesting a potential regulatory effect on inflammation-related pathways rather than direct inhibition of NF-κB activation. Conclusions: These findings suggest that BA combined with Cis inhibits Y79 retinoblastoma cell growth by inducing apoptosis and modulating NF-κB signaling. While NF-κB mRNA levels increased, reduced inflammatory cytokines and enhanced apoptosis suggest potential post-translational regulation. Further studies are needed to confirm NF-κB protein-level effects and in vivo efficacy. Full article

Breast cancer therapies have dramatically improved survival rates, but their long-term effects, especially on aging survivors, need careful consideration. This review delves into how breast cancer treatments and aging intersect, focusing on the epigenetic changes triggered by chemotherapy, radiation, hormonal treatments, and targeted therapies. Treatments can speed up biological aging by altering DNA methylation, histone modifications, and chromatin remodeling, affecting gene expression without changing the DNA sequence itself. The review explains the double-edged sword effect of therapy-induced epigenetic modifications, which help fight cancer but also accelerate aging. Chemotherapy and targeted therapies, in particular, impact DNA methylation and histone modifications, promoting chronic inflammation and shortening telomeres. These changes increase biological age, as seen in epigenetic clocks and biomarkers like p21, which also play roles in drug resistance and therapeutic decisions. Chronic inflammation, driven by higher levels of inflammatory cytokines such as TNF-α and IL-6 as well as telomere shortening, significantly contributes to the aging characteristics of breast cancer survivors. Non-coding RNAs, including microRNAs and long non-coding RNAs, are crucial in regulating gene expression and aging pathways altered by these treatments. This review explores new therapies targeting these epigenetic changes, like DNA methylation inhibitors, histone deacetylase inhibitors, and microRNA-based treatments, to reduce the aging effects of cancer therapy. Non-drug approaches, such as dietary changes and lifestyle modifications, also show promise in combating therapy-induced aging. It also highlights the clinical signs of aging-related side effects, such as heart and lung problems, endocrine and reproductive issues, and reduced quality of life. The development of comprehensive methods like the CHEMO-RADIAT score to predict major cardiovascular events after therapy is discussed. Understanding the epigenetic changes caused by breast cancer therapies offers valuable insights for creating interventions to enhance the health span and quality of life for survivors. Continued research is crucial to fully understand these epigenetic alterations and their long-term health impacts. Full article