Search Results (625)

This paper reports the first case in which a hyperlipidemic retriever (due to hypothyroidism) with a nasal tumor was successfully treated—achieving partial remission—and managed using a metronomic combination of chlorambucil (3.74 mg/m², SID) and prednisolone (0.28 mg/kg, SID) orally for 9 months at a general practice. A 35 kg spayed female golden retriever aged 8 years and 8 months with nosebleeds visited the Bundang New York Animal Hospital in July 2023 after being diagnosed with nasal carcinoma. A protocol of 4 weeks of chemotherapy followed by 1 week of rest was repeated in two cycles and continued metronomically for 9 months without pause after the two cycles. The nasal exudate was significantly reduced. The size of the nasal tumor was monitored using computed tomography (CT) imaging at a referral hospital. Since the first occurrence of epistaxis, 18 months have passed (as of January 2025) and the nasal exudate is barely visible, and the vital signs and weight of the dog remain stable. The size of the nasal tumor significantly decreased after 9 months of chemotherapy completion without moderate side effects, and all the blood work was normalized, including hypercholesteremia. This study demonstrates that, in hyperlipidemic cancer patients, a prednisolone/chlorambucil metronomic combination which is cost-effective can be an alternative to tyrosine kinase inhibitors such as sorafenib, even when excluding the price. Through a literature review, the author also investigates the effect of the hyperlipidemic state on cancer, focusing on carcinoma and vascular endothelial growth factor (VEGF), as well as the RAS-RAF-MEK pathway, which is a target for tyrosine kinase inhibitors, in order to reveal the molecular mechanism of chlorambucil metronomic chemotherapy. Also, the author investigates the molecular pathway of carcinoma development in human hyperlipidemia patients through single-cell RNA sequence analysis using open public data, and discusses the molecular action of chlorambucil. Full article

The overexpression of P-glycoprotein (P-gp) is often directly related to multidrug resistance (MDR), one of the greatest challenges in cancer treatment. This transmembrane efflux pump decreases the intracellular concentrations of chemotherapy drugs, reducing their effectiveness and resulting in treatment failure. This work used in silico methods to assess the potential of bioactive chemicals produced from mushrooms as P-gp modulators. A database comprising 211 bioactive compounds from mushrooms was investigated using molecular docking and virtual screening techniques against the P-gp structure. The compounds ergosta-4,6,8(14),22-tetraen-3-one, lucidumol A, (22E,24S)-ergosta-4,22-dien-3-one, antcin K, 3,11-dioxolanosta-8,24(Z)-diene-26-oic acid, and (22E)-19-norergosta-5,7,9,22-tetraen-3$\beta$-ol were identified as the six best candidates from our database of mushroom compounds based on their binding affinities, toxicity predictions, and pharmacological properties assessed through ADME analyses (absorption, distributions, metabolism, and excretion). These six compounds exhibited strong binding affinities, with binding energies ranging from −12.31 kcal/mol to −10.93 kcal/mol, all showing higher affinities than the control, tariquidar, which had a binding energy of −10.78 kcal/mol. Toxicity predictions indicated favorable safety profiles for all six, while ADME analyses found that all six compounds had high oral bioavailability and a low probability of acting as P-gp substrates. These results position bioactive mushroom compounds, particularly these six, as promising P-gp modulators, suggesting positive outcomes in cancer treatment. Full article

Gastrointestinal (GI) cancers represent a significant global health burden, with high morbidity and mortality often linked to late-stage detection and metastatic disease. The progression of these malignancies is critically driven by angiogenesis, the formation of new blood vessels, and the surrounding dynamic tumor microenvironment (TME), a complex ecosystem comprising various cell types and non-cellular components. This comprehensive review, based on a systematic search of the PubMed database, synthesizes the existing literature to define the intertwined roles of angiogenesis and the TME in GI tumorigenesis. The TME’s influence creates conditions favorable for tumor growth, invasion, and metastasis, but sometimes induces resistance to current therapies. Available therapeutic strategies for inhibiting angiogenesis involve antibodies and oral tyrosine kinase inhibitors, while immune modulation within the tumor microenvironment is mainly achieved through checkpoint inhibitor antibodies and chemotherapy. Creative emerging strategies encompassing cellular therapies, bispecific antibodies, and new targets such as CD40, DLL4, and Ang2, amongst others, are focused on inhibiting proangiogenic pathways more profoundly, reversing resistance to prior drugs, and modulating the TME to enhance therapeutic efficacy. A deeper understanding of the complex interactions between components of the TME is crucial for addressing the unmet need for novel and effective therapeutic interventions against aggressive GI cancers. Full article

Cutaneous and oral mucosal adverse events (AEs) are among the most common non-hematologic toxicities observed during breast cancer treatment. These complications arise across various therapeutic modalities including chemotherapy, targeted therapy, hormonal therapy, radiotherapy, and immunotherapy. Although often underrecognized compared with systemic side effects, dermatologic and mucosal toxicities can severely impact the patients’ quality of life, leading to psychosocial distress, pain, and reduced treatment adherence. In severe cases, these toxicities may necessitate dose reductions, treatment delays, or discontinuation, thereby compromising oncologic outcomes. The growing use of precision medicine and novel targeted agents has broadened the spectrum of AEs, with some therapies linked to distinct dermatologic syndromes and mucosal complications such as mucositis, xerostomia, and lichenoid reactions. Early detection, accurate classification, and timely multidisciplinary management are essential for mitigating these effects. This review provides a comprehensive synthesis of current knowledge on cutaneous and oral mucosal toxicities associated with modern breast cancer therapies. Particular attention is given to clinical presentation, underlying pathophysiology, incidence, and evidence-based prevention and management strategies. We also explore emerging approaches, including nanoparticle-based delivery systems and personalized interventions, which may reduce toxicity without compromising therapeutic efficacy. By emphasizing the integration of dermatologic and mucosal care, this review aims to support clinicians in preserving treatment adherence and enhancing the overall therapeutic experience in breast cancer patients. The novelty of this review lies in its dual focus on cutaneous and oral complications across all major therapeutic classes, including recent biologic and immunotherapeutic agents, and its emphasis on multidisciplinary, patient-centered strategies. Full article

Background: Childhood cancer is considered one of the main causes of mortality and morbidity worldwide. There is strong evidence of the oral toxic effects of oncologic treatments, but their incidence is difficult to determine. The novel therapeutic strategies in Pediatric Oncology have led to increased survival in this population, resulting in an increased incidence of long-term effects, which diminish the patient’s quality of life. Methods: The search for articles started on 5 November 2024 and ended on 5 December 2024. Following the PRISMA Statement, a total of 1266 articles were obtained, from which 13 were selected for review. All articles were considered to be of high quality. The antineoplastic treatments used in them were chemotherapy, radiotherapy, surgery and immune therapy. Results: Most articles were cohorts and case controls. Only one case report was obtained. The results revealed that the most prevalent sequelae in the pediatric population after antineoplastic treatment were enamel alterations, microdontia, dental caries, periodontal disease, gingivitis, hyposalivation, alteration of the oral microbiome, alteration of mandibular bone density and malocclusion. The lesions are different depending on the therapy used. Conclusions: Oncologic treatments in children with cancer cause multiple oral sequelae such as microdontia, dental caries, enamel alterations, salivary gland alterations, mucositis and root resorption. It cannot be concluded which therapy has the most detrimental effect as each has a different mechanism of action in the oral cavity. Full article

Peroxisome proliferator-activated receptor alpha (PPARα) is a key regulator of lipid metabolism, making its agonists valuable therapeutic targets for various diseases, including chronic peripheral neuropathy. Existing PPARα agonists face limitations such as poor selectivity, sub-optimal bioavailability, and safety concerns. We previously demonstrated that A190, a novel, potent, and selective PPARα agonist, effectively alleviates chemotherapy-induced peripheral neuropathy and CFA-induced inflammatory pain as a non-opioid therapeutic agent. However, A190 alone has solubility and permeability issues that limits its oral delivery. To overcome this challenge, in this study, four new-generation ester prodrugs of A190; A190-PD-9 (methyl ester), A190-PD-14 (ethyl ester), A190-PD-154 (isopropyl ester), and A190-PD-60 (cyclic carbonate) were synthesized and evaluated for their enzymatic bioconversion and chemical stability. The lead candidate, A190-PD-60, was further formulated as a microemulsion (A190-PD-60-ME) and optimized via Box–Behnken design. A190-PD-60-ME featured nano-sized droplets (~120 nm), low polydispersity (PDI < 0.3), and high drug loading (>90%) with significant improvement in artificial membrane permeability. Crucially, pharmacokinetic evaluation in rats demonstrated that A190-PD-60-ME reached a 16.6-fold higher Cmax (439 ng/mL) and a 5.9-fold increase in relative oral bioavailability compared with an A190-PD-60 dispersion. These findings support the combined prodrug-microemulsion approach as a promising strategy to overcome oral bioavailability challenges and advance PPARα-targeted therapies. Full article

Prostate cancer is a serious, life-threatening condition among men, usually requiring long-term chemotherapy. Due to its high efficacy, bicalutamide, a non-steroidal anti-androgen, has widespread use. However, its poor water solubility, low oral bioavailability, and nonspecific systemic exposure limit its application. To overcome these obstacles, our study explored the potential of non-carboxylated and carboxylated mesoporous carbon nanoparticles (MCN) as advanced drug carriers for bicalutamide (MCN/B and MCN-COOH/B). The physicochemical properties and release behaviour were thoroughly characterized. Functionalization with carboxylic groups significantly improved wettability, dispersion stability, as well as loading efficiency due to enhanced hydrogen bonding and π–π stacking interactions. Moreover, all systems exhibited sustained and near-infrared (NIR) triggered drug release with reduced burst-effect, compared to the release of free bicalutamide. Higher particle size and stronger drug–carrier interactions determined a zero-order kinetics and notably slower release rate of MCN-COOH/B compared to non-functionalized MCN. Cytotoxicity assays on LNCaP prostate cancer cells demonstrated that both MCN/B and MCN-COOH/B possessed comparable antiproliferative activity as free bicalutamide, where MCN-COOH/B exhibited superior efficacy, especially under NIR exposure. These findings suggest that MCN-COOH nanoparticles could be considered as a prospective platform for controlled, NIR-accelerated delivery of bicalutamide in prostate cancer treatment. Full article

Oral microbiota have been implicated in pancreatic ductal adenocarcinoma (PDAC) and may contribute to chemotherapy resistance. While previous studies attributed bacteria-induced resistance to indirect host modulation, recent findings suggest a direct mechanism. Escherichia coli expressing long-form cytidine deaminase (CDD_L) can degrade gemcitabine, a chemotherapeutic agent, into a non-toxic form, leading to resistance. In contrast, bacteria carrying short form (CDD_S) or lacking CDD did not induce resistance. This study investigates whether oral bacteria can cause gemcitabine resistance in PDAC cells through CDD-mediated degradation. Oral microbes associated with PDAC were selected based on CDD isoforms: Aggregatibacter actinomycetemcomitans carrying CDD_L, Enterococcus faecalis, Streptococcus mutans, Porphyromonas gingivalis, all carrying CDD_S, and Fusobacterium nucleatum lacking CDD. The selected microbes, along with wild-type and CDD-deficient E. coli, were co-incubated with gemcitabine to assess its degradation and PDAC cell proliferation. A. actinomycetemcomitans fully degraded gemcitabine and induced resistance. Surprisingly, CDD_S-expressing oral bacteria partially degraded gemcitabine in a strain-dependent manner. Expressing either CDD_L or CDD_S in CDD-deficient E. coli resulted in equivalent gemcitabine degradation and resistance, indicating that CDD function is independent of isoform length. These findings highlight the role of oral bacteria in gemcitabine resistance and the need for strategies to mitigate microbial-driven resistance in PDAC treatment. Full article

Background: Cachexia worsens prognosis, quality of life and chemotherapy treatment compliance of patients with lung cancer. Chemotherapy-induced cachexia has also been implicated in lowered mortality. This study aimed to evaluate the frequency of cachexia-related measures and symptoms as outcomes in lung cancer chemotherapy trial protocols and to examine how key trial characteristics influence them. Method: We conducted a cross-sectional data analysis of randomised controlled chemotherapy trials of lung cancer registered in four public trial registries between 2012 and 2023. Trial outcome measures included overall survival, treatment toxicity/side effects and cachexia-related indicators such as physical activity, weight/body mass index (BMI), dietary limitations, caloric intake and lean muscle mass. Symptom-related outcomes, including appetite loss, diarrhoea, pain, fatigue/insomnia, constipation, nausea, vomiting, dysphagia, dyspnoea and oral mucositis, were also extracted. Additionally, the number and type of performance status and assessment tool were recorded. Data were summarised descriptively. Chi-square tests were used to examine associations between trial outcomes and characteristics including cancer type, trial location, lead investigator/funding source, assessment tools and trial commencement year. A p < 0.05 was considered statistically significance. Results: Of the 335 trial protocols (non-small cell (87.2%) and small cell (12.8%)), most were from Europe (50.4%). The trial lead investigator was from industry (56.7%) followed by academia (25.1%). Allied health professional involvement was minimal (0.6%). Trial protocols mostly recorded overall survival (96.4%) and toxicity (83.9%). However, physical activity, weight/BMI, dysphagia, dyspnoea and oral mucositis were recorded in <30%, with dietary limitations, caloric intake and lean muscle mass recorded in <3% of the trials. Measures and symptoms were not associated with cancer type. Trial location was associated with the measures toxicity, physical activity and caloric intake and all symptoms. Lead investigator was associated with the measures toxicity and weight/BMI and all symptoms except for dyspnoea. Performance status and assessment tools were mentioned in 93.4% and 41.8% of the trials, respectively, with significant associations between assessment tools and outcomes, except for weight/BMI, dietary limitations, lean muscle mass, dysphagia and oral mucositis. There was a significant trend with trial commencement year for the measures physical activity (p = 0.002) and weight/BMI (p = 0.000) and all symptoms, except for appetite loss (p = 0.115) and pain (p = 0.433). Conclusions: While the reporting of measures and outcomes was generally higher compared to gastrointestinal chemotherapy cancer trials, it still faced significant under-reporting. Assessment tools should include cachexia-specific symptoms to accurately assess the quality of life in patients with lung cancer undergoing chemotherapy clinical trials. Full article

Background: Oral mucositis (OM) is a common and debilitating complication of cancer therapy, particularly in patients undergoing chemotherapy and radiotherapy. It significantly impairs quality of life and may necessitate the interruption of cancer treatment. This study aimed to evaluate the efficacy and safety of OROSOL, an oral spray device, in managing oral mucositis in pediatric patients undergoing chemotherapy or radiotherapy. Methods: This randomized, double-blind, placebo-controlled clinical trial compared OROSOL to a placebo in children with oral mucositis aged 3 to 17 years. Participants were followed for 28 days with regular medical visits. The primary endpoints were changes in the Oral Assessment Guide (OAG) scores and key symptoms (mucositis score, difficulty in oral feeding, ulceration and erythema, and pain sensation). Safety was assessed via adverse events and local tolerability. Results: Both groups were demographically balanced at baseline (p > 0.6). OROSOL demonstrated significantly greater improvements in the mucositis score beginning on Day 7 (p = 0.0122) and maintained superiority through Day 28 (p = 0.0007). Notable reductions in mucositis severity were observed, with significantly faster relief in the OROSOL group compared to the placebo (p < 0.001 for most timepoints). Oral feeding difficulty also showed a marked decline, with significant improvements starting from Day 5 (p = 0.0153). Ulceration and erythema scores significantly decreased from Day 14 onwards (p = 0.0188). Pain sensation showed a marked reduction from Day 14 (p = 0.0014). No serious adverse events were reported, and tolerability was consistent across all participants. Conclusions: OROSOL has a significant impact on reducing mucositis severity, oral feeding difficulty, ulceration, erythema, and pain. Coupled with its excellent safety profile, it is a valuable therapeutic option. This treatment is particularly beneficial for pediatric patients, ensuring improved comfort and recovery without notable adverse effects. Full article

The oral cavity harbors a highly intricate and dynamic microbial ecosystem of multiple microhabitats supporting diverse microbial populations. As the second most complex microbiome in the human body, surpassed only by the gut, the oral microbiome comprises over 1000 species. Disruptions in the microbial balance have been associated with an increased risk of both oral diseases (dental caries and periodontitis) and systemic conditions, including inflammatory diseases and certain types of cancers. In our pilot study, we purified bacterial DNA from pre-treated, saponin-based, host-depleted saliva samples and performed 16S amplicon sequencing, using Oxford Nanopore Technologies, to identify bacterial composition and investigate changes in the oral microbiota of patients with solid tumors in response to chemotherapy, either alone or in combination with immunotherapy. We found significant reductions in microbial diversity of the oral microbiota following cancer treatment, which may contribute to post-therapeutic complications such as oral mucositis. Moreover, our findings indicate that on the one hand, following chemotherapy treatment the microbial profile is characterized by an increased abundance of Streptococcus, Gemella, and Granulicatella and a decrease in the abundance of Neisseria and Veillonella. On the other hand, post combined treatment, only Streptococcus relative abundance increased, Veillonella exhibited a slight decline, and Haemophilus and Neisseria displayed a marked decrease, whilst Granulicatella and Gemella remained relatively stable. Our findings underline the impact of cancer therapy on the oral microbiome, highlighting the potential for precision-based strategies to restore microbial balance and minimize treatment-related complications. Full article

Background/Objectives: This study aimed to enhance the oral delivery and therapeutic synergy of atorvastatin (AT) and docetaxel (DT) through a metronomic schedule using a transporter-targeted nanoemulsion (NE), with the goal of improving antitumor efficacy and immune modulation. Methods: AT and DT were co-encapsulated in a NE system (AT/DT-NE#E) incorporating deoxycholic acid–DOTAP (D-TAP), biotin-conjugated phospholipid (Biotin-PE), and d-α-tocopherol polyethylene glycol succinate (TPGS) to exploit bile acid and multivitamin transport pathways and inhibit P-glycoprotein efflux. The optimized NE was characterized physicochemically and evaluated for permeability in artificial membranes and Caco-2/HT29-MTX-E12 monolayers. Pharmacokinetics, tumor suppression, and immune cell infiltration were assessed in vivo using rat and CT26.CL25 mouse models. Results: AT/DT-NE#E showed enhanced permeability of AT and DT by 45.7- and 43.1-fold, respectively, across intestinal cell models and improved oral bioavailability by 118% and 376% compared to free drugs. In vivo, oral metronomic AT/DT-NE#E reduced tumor volume by 65.2%, outperforming intravenous AT/DT. Combination with anti-PD1 therapy achieved a 942% increase in tumor suppression over the control, accompanied by marked increases in tumor-infiltrating CD45⁺, CD4⁺CD3⁺, and CD8⁺CD3⁺ T cells. Conclusions: Oral metronomic administration of AT/DT via a dual-transporter-targeted NE significantly improves drug absorption, tumor inhibition, and immune response. This strategy presents a safe and effective approach for colon cancer therapy, particularly when combined with immunotherapy. Full article

Background: Quality of life (QoL) is a critical indicator in assessing the success of oncological treatments for head and neck malignancies, reflecting their impact on physiological functions and psychosocial well-being beyond mere survival. Treatments (surgery, radiotherapy, chemotherapy) pose multiple functional and emotional challenges, and recent advancements underscore the necessity of evaluating post-treatment QoL. Objective: This literature review investigates the impact of oncological treatment on the QoL of patients with malignant head and neck cancers (oral, oropharyngeal, hypopharyngeal, laryngeal) and identifies factors influencing their QoL index. Methodology: Using a PICO framework, studies from PubMed Central were analyzed, selected based on inclusion (English publications, full text, PROM results) and exclusion criteria. The last research was conducted on 6 April 2025. From 231 identified studies, 49 were included after applying filters (MeSH: “Quality of Life,” “laryngeal cancer,” “oral cavity cancer,” etc.). Data were organized in Excel, and the methodology adhered to PRISMA standards. Results: Treatment Impact: Oncological treatments significantly affect QoL, with acute post-treatment declines in functions such as speech, swallowing, and emotional well-being (anxiety, depression). Partial recovery depends on rehabilitative interventions. Influencing Factors: Treatment type, disease stage, socioeconomic, and demographic contexts influence QoL. De-escalated treatments and prompt rehabilitation improve recovery, while complications like trismus, dysphagia, or persistent hearing issues reduce long-term QoL. Assessment Tools: Standardized PROM questionnaires (EORTC QLQ-C30, QLQ-H&N35, MDADI, HADS) highlighted QoL variations. Studies from Europe, North America, and Asia indicate regional differences in outcomes. Limitations: Retrospective designs, small sample sizes, and PROM variability limit generalizability. Multicentric studies with extended follow-up are recommended. Conclusions: Oncological treatments for head and neck malignancies have a complex impact on QoL, necessitating personalized and multidisciplinary strategies. De-escalated therapies, early rehabilitation, and continuous monitoring are essential for optimizing functional and psychosocial outcomes. Methodological gaps highlight the need for standardized research. Full article

Background: Invasive fungal infections (IFIs) are a major complication in patients with acute myeloid leukemia (AML), particularly during chemotherapy-induced neutropenia. Posaconazole is the standard drug for primary antifungal prophylaxis (PAP), but its use is limited by oral bioavailability and CYP3A4 interactions. Study Objective: This study aims to evaluate the clinical efficacy and safety of intravenous caspofungin versus oral posaconazole as PAP in AML patients during their first cycle of chemotherapy and assess their subsequent impact on clinical outcomes. Methods: A retrospective, monocentric study was conducted on 75 consecutive AML patients treated at the Federico II University Medical School of Naples, Italy (2021–2025). Patients received either caspofungin or posaconazole as PAP based on the drug–drug interaction risk or clinical conditions. IFIs were diagnosed using EORTC/MSG criteria. Logistic and Cox regression models were used to assess risk factors and overall survival (OS). Results: IFI incidence was 13.3% overall (9.4% proven/probable). No significant difference was found between the caspofungin and posaconazole groups (six vs. four IFIs; p = 0.878). Post-chemotherapy refractory AML (OR = 11.9; p = 0.003) and liver disease (OR = 30.4; p = 0.004) independently predicted IFI development. Median OS did not significantly differ in patients receiving caspofungin versus posaconazole (29.3 vs. 32.1 months, p = 0.6). Conclusions: Caspofungin appears clinically comparable to posaconazole for PAP in AML during the induction phase, especially when azole use is contraindicated. Prospective studies are warranted to refine prophylactic strategies in the era of new AML therapies. Full article

Background: Oral mucositis (OM) is a painful and debilitating stomatitis that often arises following head and neck radiotherapy, chemotherapy, or stem cell transplant, leading to treatment delays and potential patient intervention interruption. The aim of this narrative review was to explore the modalities in the management of OM. When supported by evidence, treatment is customized according to its severity. Method: A literature search was performed using the PubMed database. The search strategy consists of keywords such as “pain management”, “pain control”, and “oral mucositis”. Literature references from 1997 to 2024 were selected by the authors based on relevance to the current practice of oral mucositis pain management. Results: Fourteen studies were included in this review. Interventions were classified into pharmacological and non-pharmacological modalities. In relation to pain measurement, for grade 1 OM, topical treatments are the primary recommendation. For grades 2 to 4, where pain is moderate to severe, systemic analgesia should be administered. Honey and oral care are beneficial for OM with grades 2 to 4. Conclusions: Effective management of OM should be tailored to the severity of the condition, incorporating both pharmacological and non-pharmacological strategies. While various modalities have shown promise in relieving symptoms and enhancing the quality of life, a multifaceted, patient-centered approach remains essential. Advancing high-quality clinical trials, particularly those evaluating non-pharmacological interventions will be crucial to expanding treatment options. Future efforts should focus on personalized therapies, integration of combination treatments, adoption of standardized pain assessment tools, and long-term outcome studies to improve clinical effectiveness and optimize patient care. Full article