Search Results (2,305)

Background/Objectives: Curcumin (CUR) is well known for its therapeutic properties, particularly attributed to its antioxidant and anti-inflammatory effects in managing chronic diseases such as arthritis. While CUR application for biomedical purposes is well known, the phytochemical has several restrictions given its poor water solubility, physicochemical instability, and low bioavailability. These limitations have led to innovative formulations, with nanocarriers emerging as a promising alternative. For this reason, this study aimed to address the potential advantages of associating CUR with nanocarrier systems in managing arthritis through a scoping review. Methods: A systematic literature search of preclinical (in vivo) and clinical studies was performed in PubMed, Scopus, and Web of Science (December 2024). General inclusion criteria include using CUR or natural derivatives in nano-based formulations for arthritis treatment. These elements lead to the question: “What is the impact of the association of CUR or derivatives in nanocarriers in treating arthritis?”. Results: From an initial 536 articles, 34 were selected for further analysis (31 preclinical investigations and three randomized clinical trials). Most studies used pure CUR (25/34), associated with organic (30/34) nanocarrier systems. Remarkably, nanoparticles (16/34) and nanoemulsions (5/34) were emphasized. The formulations were primarily presented in liquid form (23/34) and were generally administered to animal models through intra-articular injection (11/31). Complete Freund’s Adjuvant (CFA) was the most frequently utilized among the various models to induce arthritis-like joint damage. The findings indicate that associating CUR or its derivatives with nanocarrier systems enhances its pharmacological efficacy through controlled release and enhanced solubility, bioavailability, and stability. Moreover, the encapsulation of CUR showed better results in most cases than in its free form. Nonetheless, most studies were restricted to the preclinical model, not providing direct evidence in humans. Additionally, inadequate information and clarity presented considerable challenges for preclinical evidence, which was confirmed by SYRCLE’s bias detection tools. Conclusions: Hence, this scoping review highlights the anti-arthritic effects of CUR nanocarriers as a promising alternative for improved treatment. Full article

Background/Objectives: Pancreatic cancer (PC) is the seventh leading cause of cancer-related deaths worldwide, with its incidence rising each year. Despite its relatively low incidence, the aggressiveness of pancreatic cancer results in high mortality, with only 12% of patients surviving five years post-diagnosis. Surgical resection remains the only potentially curative treatment, but the tumor is often diagnosed at an advanced stage. The goal of this work is to identify vulnerabilities that can affect the efficacy of treatments and improve the efficacy of therapy. Methods: MAP17 overexpression in pancreatic cancer cell lines, RT-qPCR analysis, xenografts, in vitro and in vivo treatments, analysis of data from pancreatic tumors in transcriptomic patient databases. Results: We studied the prognostic and predictive value of MAP17 (PDZK1IP1) expression in pancreatic cancer, and we found that high MAP17 mRNA expression was associated with poor prognosis. In addition, single-cell analysis revealed that high MAP17 expression was present only in tumor cells. We investigated whether the response to various antitumor agents depended on MAP17 expression. In 2D culture, MAP17-expressing pancreatic cancer cells responded better to gemcitabine and 5-fluorouracil. However, in vivo xenograft tumors with MAP17 expression showed resistance to all treatments. Additionally, MAP17-expressing cells had a high NAD pool, which seems to be effectively depleted in vivo by NAMPT inhibitors, the primary enzyme for NAD biosynthesis. Conclusions: Our findings suggest that MAP17 expression could enhance the prognostic stratification of pancreatic cancer patients. Moreover, the coadministration of NAMPT inhibitors with current treatments may sensitize tumors with high MAP17 expression to chemotherapy and improve the efficacy of chemotherapy. Full article

Acalitus simplex is an eriophyoid mite pest of the ornamental plant Ruellia simplex. Acalitus simplex compromises the esthetics of R. simplex by inducing erinea formation. Management practices for A. simplex are currently lacking. This study assessed the potential of commercial biorational (citric acid, potassium salt of fatty acids, garlic, thyme, and mineral oil) and conventional (abamectin, fenpyroximate, bifenthrin, spiromesifen) pesticides under laboratory conditions, using two types of spray applications: (A) curative, after erinea formation, and (B) prophylactic, before erinea formation. In the curative application, abamectin, garlic oil, and mineral oil were most effective; in the prophylactic application, abamectin and mineral oil showed the highest efficacies. Abamectin and mineral oil were further tested under greenhouse conditions. Both treatments effectively controlled A. simplex by preventing erinea formation over a four-week post-application period, regardless of the application type. At the end of the experiment, mites were extracted from R. simplex plants. In the curative application, significantly fewer mites were extracted from abamectin and mineral oil treatments than in the control. In the prophylactic application, mites were absent in abamectin and mineral oil treatments but present in the control. Abamectin and mineral oil can be used to manage A. simplex in landscapes. Full article

Zearalenone (ZEN), a mycotoxin commonly found in cereal crops and foods, induces testicular damage and disrupts gut microbial composition. Curcumin (CUR), a bioactive compound derived from turmeric, is known to enhance intestinal microbial balance and exhibit anti-inflammatory properties. This study aimed to investigate the mechanism by which CUR alleviates ZEN-induced reductions in sperm quality through the modulation of the gut microbiota–testis axis. Forty-eight 6-week-old Balb/c male mice were randomly assigned to four treatment groups: control (CON), CUR (200 mg/kg body weight CUR), ZEN (40 mg/kg body weight ZEN), and ZEN + CUR (200 mg/kg CUR + 40 mg/kg ZEN). The degree of sperm damage was quantified by assessing both the survival rate and the morphological integrity of the spermatozoa. CUR was found to mitigate ZEN-induced reductions in the testosterone levels, testicular structural damage, and disrupted spermatogenesis. Exposure to ZEN markedly perturbed the gut microbiota, characterized by increased relative abundances of Prevotella and Bacteroides and a concomitant reduction in Lactobacillus. These alterations were accompanied by pronounced activation of the IL-17A–TNF-α signaling axis, as demonstrated by elevated transcriptional and translational expression of pathway-associated genes and proteins. Co-administration of CUR effectively reinstated microbial homeostasis and mitigated ZEN-induced IL-17A pathway activation. In conclusion, ZEN induces testicular inflammation and reduced sperm quality by lowering testosterone levels and disrupting gut microbial balance, which drives the testicular IL-17A signaling pathway. CUR alleviates ZEN-induced testicular inflammation and sperm quality reduction by restoring beneficial gut microbes and testosterone levels. Full article

Background and Purpose: Stratification based on specific image biomarkers applicable in clinical settings could help optimize treatment outcomes for recurrent non-small cell lung cancer patients. For this purpose, we aimed to determine the clinical impact of positive delta changes (any difference above zero > 0) between baseline [¹⁸F]FDG PET/CT metrics before the first treatment course and reirradiation. Material/Methods: Forty-seven patients who underwent thoracic reirradiation with curative intent at our institute between 2013 and 2021 met the inclusion criteria. All patients had histologically verified NSCLC, ECOG (Eastern Cooperative Oncology Group) ≤ 2, and underwent [¹⁸F]FDG PET/CT for initial staging and re-staging before primary radiotherapy and reirradiation, respectively. The time interval between radiation treatments was at least nine months. Quantitative metabolic volume and intensity parameters were measured before first irradiation and before reirradiation, and the difference above zero (>0; delta change) between them was statistically correlated to locoregional control (LRC), progression-free survival (PFS), and overall survival (OS). Results: Patients were followed for a median time of 33 months after reirradiation. The median OS was 21.8 months (95%-CI: 16.3–27.3), the median PFS was 12 months (95%-CI: 6.7–17.3), and the median LRC was 13 months (95%-CI: 9.0–17.0). Multivariate analysis revealed that the delta changes in SULpeak, SUVmax, and SULmax of the lymph nodes significantly impacted OS (SULpeak p = 0.017; SUVmax p = 0.006; SULmax p = 0.006), PFS (SULpeak p = 0.010; SUVmax p = 0.009; SULmax p = 0.009), and LRC (SULpeak p < 0.001; SUVmax p = 0.003; SULmax p = 0.003). Conclusions: Delta changes in SULpeak, SUVmax, and SULmax of the metastatic lymph nodes significantly impacted all clinical endpoints (OS, PFS and LRC) in recurrent NSCLC patients treated with reirradiation. Hence, these imaging biomarkers could be helpful with regard to patient selection in this challenging clinical situation. Full article

Background/Objectives: The global population of individuals aged ≥ 80 years is rapidly growing, leading to an increasing incidence of cancer diagnoses in this age group. While stereotactic body radiotherapy (SBRT) has proven effective in treating pulmonary oligometastases, patients over 80 remain underrepresented in clinical analyses. This study aimed to evaluate clinical outcomes and toxicity of SBRT for pulmonary oligometastases in octogenarians. Methods: This retrospective, single-centre analysis included 34 patients aged ≥ 80 years treated with SBRT for histologically confirmed pulmonary oligometastases between 2010 and 2024. Results: A total of 46 pulmonary metastases were treated with curative intent using fractionation schemes of 3 × 15 Gy, 6 × 8 Gy, or 10 × 6 Gy. Median biologically effective dose (BED10) was 112.5 Gy. Follow-up included regular CT imaging and toxicity assessment according to CTCAE. With a median follow-up of 22.6 months, 1-, 2-, and 3-year local control (LC) rates were 95.2%, 95.2%, and 90.2%, respectively. Median overall survival (OS) was 46.6 months, with 1-, 2-, and 3-year OS rates of 78.4%, 71.4%, and 59.5%. Progression-free survival (PFS) at 1, 2, and 3 years was 63.4%, 51.6%, and 47.3%, respectively. No grade ≥ 3 toxicities were observed. Grade 2 pneumonitis and dermatitis occurred in 2.9% each and were well managed. Asymptomatic rib fractures were detected in 5.9% of patients. No significant predictors for LC, PFS, or OS were identified in univariate analysis. Conclusions: SBRT for pulmonary oligometastases in patients ≥ 80 years is feasible, safe, and effective. High local control, favourable cancer-specific survival, and minimal toxicity support its use as a curative-intent treatment in this growing patient population. These findings contribute important site- and age-specific evidence and support the inclusion of very elderly patients in future prospective SBRT trials. Full article

The global burden of hepatitis B virus (HBV) remains high, with ongoing concerted efforts to eliminate viral hepatitis as a public health concern by 2030. The absence of curative treatment against HBV makes it an active area of research to further study HBV pathogenesis. In vitro cell culture systems are essential in exploration of molecular mechanisms for HBV propagation and the development of therapeutic targets for antiviral agents. The lack of an efficient cell culture system is one of the challenges limiting the development and study of novel antiviral strategies for HBV infection. However, the evolution of cell culture systems to study HBV pathogenesis and treatment susceptibility in vitro has made a significant contribution to public health. The currently available cell culture systems to grow HBV have their advantages and limitations, requiring further optimization. The discovery of sodium taurocholate co-transporting polypeptide (NTCP) as a receptor for HBV was a major breakthrough for the development of a robust cell model, allowing the study of de novo HBV infection through NTCP expression in the HepG2 hepatoma cell line. This review is aimed at highlighting the evolution of cell culture systems to study HBV pathogenesis and in vitro treatment susceptibility. Full article

Background/Objectives: Primary malignant lung tumors in children are rare and diagnostically challenging. This study presents a single-center experience in the diagnosis and treatment of these tumors, emphasizing the role of histopathological and genetic profiling in informing individualized therapeutic strategies. Methods: We retrospectively reviewed records of seven pediatric patients (ages 2–18) treated from 2015 to 2025. Diagnostics included laboratory tests, chest CT, bronchoscopy, and histopathological/immunohistochemical analysis. Treatment primarily involved surgical resection, complemented by chemo-, radio-, or targeted therapies when indicated. Results: Inflammatory myofibroblastic tumor (IMT) represented the most commonly diagnosed entity (3/7 cases). The tumors presented with nonspecific symptoms, most frequently dry cough. Tumor type distribution was age-dependent, with aggressive forms such as pleuropulmonary blastoma predominantly affecting younger children, whereas IMT and carcinoid tumors were more common in older patients. Surgical resection remained the mainstay of treatment in the majority of cases. Bronchoscopy served as a valuable adjunct in the initial management of tumors exhibiting intraluminal growth, allowing for direct visualization, tissue sampling, and partial debulking to alleviate airway obstruction. In patients with an initially unresectable IMT harboring specific gene fusion rearrangement (e.g., TFG::ROS1), neoadjuvant targeted therapy with crizotinib enabled adequate tumor shrinkage to allow for subsequent surgical resection. Two patients in the study cohort died as a result of disease progression. Conclusions: A multidisciplinary diagnostic approach—integrating radiologic, bronchoscopic, histopathological, and genetic evaluations—ensures high diagnostic accuracy. While conventional treatments remain curative in many cases, targeted therapies directed at specific molecular alterations may offer essential therapeutic options for selected patients. Full article

Background: Despite advances in treatment, oral squamous cell carcinoma (OSCC) remains associated with high recurrence and mortality rates. Traditional TNM staging, while foundational, may not fully capture tumor aggressiveness. This study aimed to identify clinical and histopathological predictors of survival to enhance risk stratification and guide treatment planning in OSCC patients. Methods: A retrospective study of 100 patients with confirmed OSCC treated surgically with curative intent between January 2019 and January 2024 was analyzed. Clinicopathologic variables—including tumor volume, angioinvasion, perineural invasion, lymphatic invasion, and nodal status—were evaluated. Disease-specific survival (DSS) was assessed using Kaplan–Meier estimates, Cox regression, and logistic regression models. Results: The cohort had a mean age of 62.1 years, with a 46% OS rate and 43% DSS at study end. Perineural invasion (44%) and lymphatic invasion (42%) were the most common invasive features. Kaplan–Meier analysis revealed significantly reduced DSS in patients with angioinvasion, perineural invasion, and pN+ status. Multivariate logistic regression identified perineural invasion (OR = 3.93, p = 0.0023) and pN+ status (OR = 2.74, p = 0.0284) as independent predictors of cancer-specific mortality. Tumor volume was significantly associated with lymphatic invasion but not directly with DSS. Conclusions: Perineural invasion, angioinvasion, lymph node involvement, and tumor volume are important prognostic markers in OSCC, offering critical information beyond TNM staging. Incorporating these features into risk assessment models could improve prognostic accuracy and inform more individualized treatment strategies for high-risk OSCC patients. Full article

Most patients with non-small-cell lung cancer (NSCLC) present with advanced/metastatic disease at diagnosis, and molecular profiling is critical in guiding treatment decisions. This retrospective cohort study aimed to characterize EGFR mutations (EGFRm) in advanced/metastatic NSCLC patients, treatment patterns, and real-world outcomes. Adults diagnosed between 2018 and 2021 and treated at a Comprehensive Care Center were included. Time-to-event outcomes were analyzed using the Kaplan–Meier method. A total of 110 patients were included, with a median age of 69.0 years (range, 37–93), 76.4% female, and 83.2% non-smokers. About 97.3% had adenocarcinomas, with 93.6% at stage IV, 40.9% with ≥ three metastatic sites (brain metastases in 24.5%), 33.6% ECOG 2–4, and 58.2% with an EGFR exon-19 deletion. A minority started supportive care or curative-intent treatment, and 81.8% underwent first-line palliative systemic therapy (TKIs, 91.1%; chemotherapy, 8.9%). Median real-world overall survival (rwOS) was 18.9 months (95% CI, 13.8–28.1). Worse rwOS was observed in patients with ECOG 2–4 versus ECOG 0–1 (10.3 vs. 22.8 months; HR 1.82, 95% CI 1.17–2.85; p = 0.008) and in patients with exon-21 L858R versus exon 19 deletions (15.8 vs. 24.2 months; HR 1.59, 95% CI 1.00–2.54; p = 0.048). In patients treated with palliative systemic treatment, median progression-free survival was 10.9 months (95% CI, 8.8–13.6). This study provides important insights regarding real-world characteristics, treatment patterns, and outcomes from a cohort of EGFRm advanced/metastatic NSCLC patients. Full article

Background/Objectives: Biliary tract cancers (BTCs) are aggressive malignancies with a poor prognosis. Surgery remains the only curative option, yet recurrence rates are high, and the role of adjuvant chemotherapy remains debated. This study aims to evaluate the impact of adjuvant chemotherapy and prognostic factors on survival outcomes in resected BTCs. Methods: We conducted a retrospective multicenter study analyzing patients diagnosed with intrahepatic (iCCA) and extrahepatic cholangiocarcinoma (eCCA) or gallbladder cancer (GBC) who underwent curative-intent surgical resection between 1999 and 2023. Demographic, clinicopathological, and treatment data were collected from institutional databases. Survival outcomes were assessed using Kaplan–Meier analysis, and prognostic factors were identified through Cox proportional hazards regression. Results: A total of 155 patients were included, with a median follow-up of 84.6 months. The cohort comprised 38.7% iCCA, 31.6% eCCA, and 29.7% GBC. R0 resection was achieved in 77.4% of cases, while lymph node involvement was present in 39.4%. Median overall survival (OS) significantly varied by stage (p < 0.001), ranging from >60 months for stage I to ~12 months for stage IVA. Eastern Cooperative Oncology Group (ECOG) performance status (PS) emerged as the strongest independent prognostic factor for OS (p < 0.001). Adjuvant chemotherapy, administered to 49.0% of patients, did not significantly improve OS in the overall cohort (p = 0.899). However, subgroup analyses suggested potential benefits in iCCA and eCCA but not in GBC. High CA19-9 levels and vascular invasion were associated with poorer survival outcomes. Conclusions: This study highlights the prognostic significance of ECOG PS, resection margin status, lymph node involvement, and CA19-9 levels in resected BTCs. The lack of a clear survival benefit from adjuvant chemotherapy underscores the need for improved therapeutic strategies. Future research should focus on refining risk stratification models and identifying more effective adjuvant treatments to enhance long-term survival outcomes in patients with BTC. Full article

Background and Objectives: The combined use of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is employed for the treatment of peritoneal carcinomatosis (PC). To achieve optimal cytoreduction, there may be a need for extensive resection and subsequent reconstruction of urologic structures. This study was designed to evaluate the outcomes of urinary tract resection or repair performed in CRS/HIPEC in terms of operative and oncological outcomes. Materials and Methods: After institutional review board approval, data from 550 consecutive patients who underwent the CRS/HIPEC procedure from January 2007 to July 2018 at six university hospitals was retrieved from prospectively maintained databases. Data from patients who had a concomitant curative resection and reconstruction of the bladder, ureter, or kidney during the CRS/HIPEC procedure were analyzed retrospectively. Results: A total of 50 out of 550 patients had undergone resection with a repair of the urinary tract due to tumor invasion or iatrogenic injury. Postoperative (within 30 days) urologic complications were observed in 9 of the 50 patients. It was found that having a peritoneal cancer index (PCI) equal to or greater than 20 (p < 0.009) was the sole significant risk factor associated with the occurrence of early urinary complications. Survival time post CRS/HIPEC treatment did not significantly differ between patients with and without urologic complications (median overall survival: 23 vs. 27 months, p = 0.683). Conclusions: Despite urinary tract issues during CRS/HIPEC for PC, including a PCI over 20 and potential complications from resection or repair, the procedure still offers significant survival benefits. Full article

Background: Paediatric hepatocellular carcinoma (HCC), including its fibrolamellar variant (FLC), is a rare malignancy with distinct biological behaviour and limited therapeutic options. While complete surgical resection is a key determinant of survival, many patients present with unresectable tumours at diagnosis. The role of neoadjuvant chemotherapy in improving resectability, particularly in histologically distinct subtypes, remains inconclusive. Methods: We retrospectively analysed 43 patients (<18 years) with histologically confirmed conventional HCC (cHCC, n = 27) or FLC (n = 16) enrolled in the German Pediatric Liver Tumour Registry. We assessed clinical characteristics, treatment response, surgical outcomes, and survival. Special focus was placed on the impact of neoadjuvant chemotherapy in initially unresectable tumours. Results: FLC and cHCC exhibited significant differences in clinical presentation, such as age of presentation, AFP elevation, or presence of underlying liver disease. Although overall survival did not significantly differ between groups, cHCC tumours showed a markedly higher response to chemotherapy (62.5% partial remission vs. 0% in FLC). Complete resection (R0) was achieved in 77% of all patients and was the strongest predictor of survival. Importantly, a subset of cHCC patients who initially had unresectable tumours became eligible for curative surgery following neoadjuvant chemotherapy. Notably, delayed resection after chemotherapy led to outcomes comparable to those with upfront surgery, whereas progression during chemotherapy was associated with a universally poor prognosis. Conclusions: This study supports upfront resection as the preferred strategy in paediatric HCC and FLC whenever feasible. In cHCC, neoadjuvant chemotherapy demonstrated a favourable response profile and contributed to secondary resectability in a subset of initially unresectable cases, supporting a potential role within a multimodal treatment approach. In contrast, FLC showed limited responsiveness to current systemic therapies. These findings emphasise the importance of histology-specific strategies and highlight the ongoing need for more effective systemic options, particularly for unresectable FLC. Full article

Background: Circadian rhythms regulate critical cellular processes, including DNA repair and cell cycle dynamics, potentially influencing the effectiveness of radiotherapy (RT). This study evaluated whether RT timing impacts clinical outcomes and symptom burden in prostate cancer patients. Patients/Methods: This retrospective study (n = 336, median follow-up 55 months) included men who received curative intent external beam RT between 2010 and 2019 (median age 69, 69% black, median PSA 11.3, 40% with Gleason 8–10). Treatment times (TTs) were averaged and analyzed by quartile/median. Outcomes included freedom from biochemical failure (FFBF) and distant metastasis (FFDM), GI and GU toxicity, and quality of life (QOL). Subgroup analyses by race and hormone therapy status were performed. Results: Across the overall cohort, TT was not associated with FFBF or FFDM. However, in white men, earlier TTs were significantly associated with higher 5-year FFBF (89% vs. 67%, p = 0.0139) and FFDM (93% vs. 72%, p = 0.0268). In the multivariate analysis (MVA), TT was not associated with FFBF or FFDM for all men, but in white men, earlier TT was associated with improved FFBF (HR 2.8, p = 0.06) in a model also including risk category (p = 0.21). Overall, no significant differences were observed for grade 2–3+ toxicity and TT. Trends for inferior QOL, and worse grade 2+ (p = 0.2) and 3+ GU toxicity (p = 0.1) were observed for later TTs. In white men, bowel, urinary continence, and irritative/obstructive urinary QOL were worse with later TTs (p < 0.05). Conclusions: TT may influence clinical outcomes and symptom burden, particularly in white men. These findings underscore the potential of chronoradiotherapy as a personalized treatment strategy and highlight the need for prospective trials. Full article

Polycystic liver disease (PLD) is a rare genetic disorder characterized by the development of >10 fluid-filled cysts in the liver. While PLD can occur in isolation, it is most commonly associated with autosomal dominant polycystic kidney disease, adding complexity to its management. PLD is often asymptomatic but can lead to hepatomegaly, causing symptoms such as abdominal distension, pain and discomfort, early satiety, gastroesophageal reflux, and malnutrition, ultimately affecting patients’ quality of life. Current treatment strategies, including pharmacological and interventional approaches, focus on reducing liver volume and alleviating symptoms. However, management remains largely symptomatic, as no definitive therapies exist to halt cyst progression. Liver transplantation is the only curative option for patients with severe, progressive disease and refractory complications. The EASL guidelines recognize that PLD-related symptoms, primarily due to hepatomegaly, can contribute to involuntary weight loss and recommend assessing symptomatic patients for malnutrition and sarcopenia. Although evidence suggests that patients with PLD may be at risk of malnutrition, original data on the quality and extent of nutritional alterations remain scarce. The potential influence of nutrition on disease progression, symptom burden, and overall well-being is also largely unexplored. Given these knowledge gaps, addressing nutritional challenges, such as early satiety, is essential for optimizing symptom management and maintaining overall nutritional status. This review outlines a possible pathophysiology of malnutrition, specific dietary considerations and recommendations, and weight management in patients with PLD. Additionally, dietary complexities in patients with concurrent renal involvement are discussed, offering a practical framework for clinicians and dietitians in managing this challenging condition. Full article