Search Results (286)

Purpose: To investigate whether the season in which photorefractive keratectomy (PRK) with mitomycin C (MMC) is performed influences postoperative corneal transparency considering seasonal variations in ultraviolet (UV) exposure. Methods: This retrospective study included 100 eyes of 50 patients who underwent MMC-assisted PRK for myopic refractive error. Patients were divided into two groups based on the season of surgery: winter (November–April, low UV exposure) and summer (May–October, high UV exposure). All patients were evaluated preoperatively and at 12 months postoperatively. Corneal transparency was objectively assessed using Scheimpflug-based corneal densitometry obtained with the Pentacam system, focusing on the central (0–2 mm) and paracentral (2–6 mm) zones. Postoperative densitometry values were compared between seasonal groups. Results: Corneal densitometry values showed a significant reduction postoperatively compared with preoperative measurements in both central and paracentral zones. When comparing seasonal groups, no statistically significant differences were observed in postoperative densitometry values between eyes operated on during summer and winter months. No clinically detectable corneal haze was observed in any patient throughout the follow-up period. Conclusions: Surgical season did not significantly influence postoperative corneal densitometry or clinically detectable haze formation after MMC-assisted PRK for low-to-moderate myopia, suggesting that deferral during high-UV months may not be necessary with standard postoperative UV protection. Full article

Polymerised type I collagen (polymerised collagen) and pirfenidone (PFD) reduce fibrosis. However, their use as pharmacological monotherapy for tracheal stenosis (TS) has not been evaluated. This study aimed to evaluate the effects of polymerised collagen or PFD, used either as monotherapy for TS, or in combination with tracheal resection (TRE) on the development of restenosis (RTS), apoptotic body (AB) formation, production of profibrotic proteins, ITGβ1 expression and metalloproteinase (MMP) expression in a rat model of TS. Eighty Wistar rats underwent TS. Forty received monotherapy (treatment A) with: saline solution (SS), mitomycin C (MMC), polymerised collagen, or PFD. The other forty received TRE combined with the pharmacological treatment (treatment B). They were clinically evaluated. Four weeks after treatment, AB formation, ITGβ1, TGF-β, profibrotic proteins, and MMPs expression were assessed in TS tissue and post-TRE tissue. Our findings showed that treatment A with polymerised collagen or PFD did not reverse TS but halted its progression, reduced the expression of profibrotic proteins, ITGβ1 and MMP-9, and increased AB and MMP-1. Treatment B promoted normal tracheal healing and prevented RTS. We conclude that the use of polymerised collagen or PFD as monotherapy does not reverse TS. However, they halt disease progression by modulating the production of profibrotic factors. In combination with TRE, these agents promote favourable tracheal healing and prevent RTS. Full article

Cell migration is a fundamental process in cancer progression, playing a central role in tumor invasion and metastasis. This highly coordinated behavior is regulated by dynamic interactions between cancer cells and extracellular environment. Among the different tumor types, glioblastoma (GB) represents a particularly aggressive form of cancer in which enhanced migratory capacity is a key determinant of diffuse brain infiltration, tumor recurrence, and poor prognosis. In this context, extracellular vesicles (EVs) have emerged as important mediators, regulating cell migration in several cancer types, including GB. EVs are lipid bilayer-enclosed nano- and micro-sized particles, containing various bioactive molecules that can target specific recipient cells, thereby modulating cellular properties, including the migratory behavior. Among the available methods for studying cell migration, the wound healing assay is the most widely used. Although simple, cost-effective and not requiring sophisticated equipment, its reliability and reproducibility can be affected by technical variability and the diversity of existing protocols. Here, we present an optimized protocol for executing and analyzing a cellular wound healing assay designed to assess EV-mediated migration in GB cells. The protocol incorporates the use of silicone culture inserts to enhance wound homogeneity and reproducibility, together with continuous Mitomycin C incubation to inhibit cell proliferation without inducing cytotoxicity, enabling specific assessment of cell migration. We outline a step-by-step description of the procedure, detailing all required materials and equipment and highlighting critical steps, checkpoints, and key parameters. This method provides a robust framework for reproducible wound healing assays to investigate EV effects on GB cell migration. Full article

Background: Head and neck squamous cell carcinoma (HNSCC) is among the top 10 most common cancer entities worldwide. For patients with locally advanced, non-metastatic HNSCC, the standard of care treatment often includes concomitant chemoradiotherapy with cisplatin. However, a considerable number of these patients are cisplatin-ineligible. To inform treatment selection for cisplatin-unfit patients undergoing radiotherapy (RT) for HNSCC, a network meta-analysis was performed. Method: In November 2023 a systematic search was conducted and updated in January 2026 searching four electronic databases (Medline, Web of Science, Cochrane Library, and Scopus) to identify randomized controlled trials (RCTs) analyzing overall survival (OS), progression-free survival (PFS), locoregional control (LC) and adverse events (AE) of RT combined with chemo-/immunotherapy with relevance to treatment selection in cisplatin-ineligible patients with HNSCC. Results: From all (15,551) search results, 52 publications concerning 28 RCTs reporting on approximately 7000 patients were included. The therapeutic concepts in the experimental group included all combinations of RT with concurrent systemic therapy, excluding cisplatin-based regimens, and were compared with any control treatment. All studies had sufficient quality for inclusion. None of the systemic agents showed a significant improvement in OS, PFS, or LC compared to cisplatin. Carboplatin + 5-FU and mitomycin C + 5-FU improved LC compared to hyperfractionated accelerated radiotherapy (HART). Compared to cisplatin, durvalumab and cetuximab were associated with less dysphagia, cetuximab with less renal impairment, and panitumumab and cetuximab with less weight loss. Conclusions: Carboplatin + 5-FU and Mitomycin C + 5-FU achieve superior LC compared to HART. Targeted therapy and immunotherapy were associated with less severe AEs. Full article

Transmitochondrial cybrid technology is a key approach for elucidating the effects of mitochondrial DNA (mtDNA) mutations in defined nuclear genetic backgrounds and for studying nuclear–mitochondrial interactions. However, its application is limited by the availability of suitable recipient cell lines and by technically demanding enucleation procedures. We report three advances in cybrid technology: (1) enucleation using mitomycin C, a widely used agent for generating feeder layers in stem cell culture, which does not depend on cell attachment and provides a gentler alternative to actinomycin D; (2) selection of cybrids using mitochondrial uncouplers, which can reduce background survival of non-cybrid cells; and (3) cryopreservation of enucleated donor cells in liquid nitrogen, preserving fusion competence and increasing experimental flexibility. Additionally, we validate newly developed mtDNA-free (ρ⁰) derivatives of HCT116, HT1080, and U2OS cell lines as recipients for cybrid generation. These advances facilitated donor cell preparation, improved cybrid selection, and enhanced experimental flexibility, including the demonstration of preserved fusion competence of enucleated HeLa cells after 10 years of cryostorage. The ρ⁰ derivatives of HCT116, HT1080, and U2OS cells were confirmed as effective recipients. Together, these improvements enhance the efficiency and accessibility of transmitochondrial cybrid technology and are expected to facilitate its broader application. Full article

Background and Objective: Transurethral resection of bladder tumor (TURBT) is the standard for non-muscle-invasive bladder cancer (NMIBC), yet recurrence rates remain high. This study evaluates the safety, tolerability, and efficacy of neoadjuvant intravesical mitomycin C (neoMMC) before TURBT in reducing recurrence and improving surgical outcomes. Methods: This randomized phase III trial enrolled patients with primary or recurrent NMIBC. Participants were randomized 1:1 to a neoadjuvant group receiving two instillations of MMC (day −14 and −7) before TURBT, or a control group undergoing standard TURBT without neoadjuvant treatment. The primary endpoint was 12-month recurrence-free survival (RFS). Secondary endpoints included surgical quality (complete resection, cauterization only, absence of residual tumor) and safety. Exploratory endpoints included histopathologic response and time to recurrence. Key Findings and Limitations: Among 95 patients (48 neoMMC, 47 controls), baseline characteristics were balanced. After a median follow-up of 19.4 months, recurrences occurred in 9 StA and 4 NeoA patients, with one progression to MIBC in the NeoA arm. RFS did not differ significantly between groups at 12 or 18 months. Neoadjuvant MMC was well tolerated, with only grade 1–2 AEs. Exploratory microbiota analyses suggested that neoadjuvant MMC modulated urinary microbial diversity and was associated with a microbiota profile more similar to that observed in non-recurrent patients. Limitations include single-center design and relatively short follow-up. Conclusions and Clinical Implications: Neoadjuvant intravesical MMC before TURBT was feasible and well tolerated in patients with NMIBC, with no unexpected safety signals. In this prematurely terminated and underpowered trial, no significant improvement in RFS was observed. Larger adequately powered studies are needed to clarify the oncologic efficacy of this approach. Full article

Background: Conjunctival melanoma is a rare but potentially aggressive ocular surface malignancy characterized by frequent local recurrence and risk of metastatic spread. In carefully selected cases, depending on tumor extent, clinical course, and patient condition, management may require balancing oncologic control with preservation of the globe, visual function, and quality of life. Case Presentation: We report the case of a 78-year-old woman with amelanotic conjunctival melanoma of the left eye. Initial treatment consisted of wide local excision using a no-touch technique, conjunctival autograft reconstruction, and adjuvant topical Mitomycin C (MMC). During a 10-year follow-up period, the patient developed multiple local recurrences requiring repeated surgical excisions and additional MMC therapy. Despite the chronic relapsing course, useful visual function and globe preservation were maintained. In December 2024, a subcutaneous lesion of the upper eyelid was detected and histopathologically confirmed as locoregional metastasis from the primary conjunctival melanoma. Given the patient’s advanced age, preserved visual function, absence of documented distant metastatic disease, and overall clinical context, management continued with a conservative, eye-preserving approach. Conclusions: This case illustrates that prolonged eye preservation may be achievable in carefully selected patients with recurrent conjunctival melanoma through repeated conservative management. However, this strategy does not eliminate the risk of delayed progression and requires individualized decision-making together with long-term surveillance. Full article

Hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases relies primarily on DNA-damaging agents whose efficacy depends on sustained cytotoxic exposure. Whether brief treatment can induce durable transcriptional remodeling remains unclear. Mithramycin A (MA) is a GC-rich DNA-binding agent with transcriptional regulatory activity involving chromatin-associated pathways. Here, we investigated the molecular and functional consequences of a single 90-min HIPEC-mimetic MA exposure in colorectal cancer models. RNA sequencing revealed extensive and coordinated transcriptional remodeling, affecting a substantial fraction of expressed genes and producing a response qualitatively distinct from mitomycin C. MA selectively suppressed key chromatin-associated regulatory factors, including DNMT1, JARID2, and HDAC4, while coordinately activating canonical cyclin-dependent kinase inhibitors CDKN1A, CDKN1C, and CDKN2C. Gene set enrichment analysis demonstrated enrichment of G2/M checkpoint pathways and suppression of oncogenic gene networks. These molecular changes translated into sustained inhibition of clonogenic growth and activation of caspase-dependent apoptosis following drug washout, with hyperthermia potentiating apoptotic signaling. Collectively, these findings indicate that brief MA exposure induces selective modulation of chromatin regulators and durable transcriptional reorganization, supporting modulation of chromatin regulatory networks as a potential therapeutic strategy for HIPEC-based colorectal cancer therapy. Full article

Background: Localized soft tissue sarcoma (STS) is primarily treated with surgical resection with or without radiotherapy (RT), while the role of chemotherapy (CT) as a radiosensitizer remains unclear. We report our single-institution experience with combined chemoradiotherapy (CCRT) in treating localized STS. Methods: We conducted a retrospective analysis of patients with localized STS treated at Mayo Clinic with mitomycin, cisplatin, and doxorubicin (MitoAP) concurrently with RT between 1/1/85 and 12/12/19. Results: We identified 179 patients (median age 58 years; median tumor size 9.5 cm), with 83.8% of tumors located in the extremities or trunk. Among them, 77.1% received perioperative CT in addition to CCRT, with 95% of those treated in the neoadjuvant setting. Median RT dose was 50 Gray. The 5-year disease-specific survival (DSS) was 77.9% (95% confidence interval, CI: 70.8–83.4%). The addition of perioperative CT to CCRT was associated with improved DSS compared with CCRT alone (p = 0.01, Hazard Ratio, HR: 0.48, 95% CI: 0.27–0.85). Median post-CCRT tumor viability was 30% and did not differ by CT use (p = 0.39), but varied significantly by histology (p < 0.001). Conclusions: Our institutional protocol utilizing two cycles of MitoAP with RT was well tolerated. DSS in our cohort was similar to historical data using perioperative RT alone, suggesting no clear benefit from CCRT. However, the majority of patients in our cohort were classified as high risk, which may have attenuated a potential survival benefit in the absence of appropriate comparative controls. Furthermore, additional perioperative CT to CCRT was associated with improved DSS and differential histology-specific responses in tumor viability, suggesting that a more aggressive neoadjuvant and perioperative approach may be beneficial in selected patients. Full article

Leaves of Actinidia chinensis Planch. var. deliciosa (A.Chev.) A.Chev. (A. deliciosa) represent agro-industrial byproducts with potential for valorization. The present study evaluated the metabolomics profiling, cytotoxicity, genotoxicity, and antigenotoxicity of the methanolic extract of A. deliciosa leaves. The metabolomics profiling was determined using an untargeted metabolomic approach employing UPLC-HRMS. Cytotoxicity, genotoxicity, and antigenotoxicity were assessed in Chinese hamster ovary K1 (CHO-K1) cells using the in vitro cytokinesis-block micronucleus (CBMN) assay. The metabolic profile of A. deliciosa leaf extracts revealed the presence of three major classes of secondary/specialized metabolites: proanthocyanidins, flavonols, and triterpenoid saponins. Medium-polar metabolites were monomeric fla-van-3-ols, such as (+)-catechin and (−)-epicatechin, oligomeric procyanidins and prodelphinidins, and flavonols. Certain glycosylated flavonols and their derivatives, such as myricetin, quercetin, and kaempferol. Low-polarity metabolites were characterized by low-polarity triterpenoids such as maslinic, corosolic, oleanolic, and ursolic acids. At concentrations of 37.5, 75, and 150 µg/mL, the extract did not significantly increase micronuclei frequency compared to untreated control cells, indicating an absence of genotoxic potential. Moreover, co-treatment of CHO-K1 cells with the extract and mitomycin C (MMC) at 0.025 µg/mL resulted in a significant reduction in micronuclei formation induced by MMC at concentrations of 75 and 150 µg/mL, suggesting antigenotoxic activity likely associated with the phytochemical constituents presented in the extract. Full article

Introduction and Importance: Colorectal adenocarcinoma typically metastasizes to the liver and lungs, with pleural, breast, or osseous involvement being exceedingly rare. Here, we report an unusual case of rectal adenocarcinoma metastasizing to the chest wall with simultaneous involvement of the lung, pleura, ribs, and subcutaneous breast tissue, forming a dominant giant metastasis (25 × 18 × 16 cm) accompanied by additional satellite lesions between the ribs and pectoral muscles, as well as intrapulmonary nodules. Presentation of case: The patient underwent radical resection including rib excision, followed by hyperthermic intrathoracic chemotherapy (HITHOC) with mitomycin. Chest wall integrity was restored using a synthetic mesh and titanium plating, ensuring both oncologic clearance and structural stability. Multimodal therapy also included neoadjuvant chemotherapy with bevacizumab, which was continued postoperatively. Clinical discussion: This case underscores the critical role of a multidisciplinary strategy in managing rare and aggressive metastatic patterns of colorectal cancer. In selected patients, a combination of systemic therapy, extensive surgical resection, advanced reconstruction, and regional chemotherapy may offer the potential for short-term local disease control. Conclusions: The radical excision of the giant tumour enabled continuation of systemic therapy under the national drug programme, was associated with short-term local control, and improved the patient’s quality of life. Full article

Background/Objectives: Retinoblastoma represents the most common intraocular malignancy in childhood; however, the clinical applicability of mitomycin C (MMC) is restricted by dose-dependent ocular toxicity. Consequently, the development of pharmacological strategies that sensitize tumor cells to MMC while allowing dose reduction remains an unmet therapeutic objective. In this context, quercetin, a bioactive flavonoid with pleiotropic anticancer properties, has emerged as a potential chemosensitizing agent. Methods: Human retinoblastoma cell lines Y79 and WERI-Rb1 were exposed to MMC and quercetin, administered either individually or in fixed-ratio combinations. Cytotoxic responses were quantified through dose–response modeling and IC₅₀ determination following 24 and 48 h of treatment. Drug–drug interactions were quantitatively characterized using the Chou–Talalay combination index (CI) approach and isobologram analysis. Cell cycle distribution was assessed by propidium iodide (PI)-based flow cytometric analysis to evaluate treatment-associated alterations in cell cycle progression. Apoptotic cell death was assessed by Annexin V-FITC/PI flow cytometry, while transcriptional modulation of genes associated with apoptosis, cell cycle regulation, and oxidative stress (BAX, BCL-2, TP53, CASP3, CDKN1A, and HMOX1) was evaluated by qRT-PCR. Modulation of tumor-supportive signaling was examined by measuring VEGF and IL-6 secretion. Translational relevance was further investigated using a three-dimensional (3D) tumor spheroid model, and the functional contribution of reactive oxygen species (ROS) was interrogated through N-acetyl-L-cysteine (NAC) rescue experiments. Results: Quercetin significantly enhanced the cytotoxic activity of MMC in both retinoblastoma cell lines, with CI values below 1 across IC₅₀–IC₉₀ effect levels, indicating a synergistic pharmacological interaction. PI–FACS analysis revealed that combined MMC and quercetin treatment induced a pronounced accumulation of cells in the G2/M phase, consistent with cell cycle arrest, with a more marked effect observed in Y79 cells compared with WERI-Rb1 cells. Combination treatment resulted in a pronounced increase in apoptotic cell populations compared with single-agent exposure and triggered a coordinated pro-apoptotic transcriptional response, characterized by increased expression of BAX, TP53, CASP3, CDKN1A, and HMOX1, alongside suppression of BCL-2 and a marked shift in the BAX/BCL-2 ratio. Concurrently, VEGF and IL-6 secretion were significantly reduced, reflecting attenuation of pro-angiogenic and pro-inflammatory signaling. Notably, synergistic cytotoxicity was maintained in 3D tumor spheroids, where combined treatment induced spheroid shrinkage, architectural disruption, and reduced viability. NAC pretreatment diminished ROS accumulation and partially restored cell viability, indicating that oxidative stress contributes to, but does not solely account for, the observed synergistic cytotoxic effect. Conclusions: Collectively, these findings indicate that quercetin appears to function as an effective chemosensitizing adjuvant to MMC in retinoblastoma models, through transcriptional changes consistent with p53-associated apoptotic signaling at the transcriptional level, G2/M cell cycle arrest, and partial involvement of ROS-related cellular stress responses, along with suppression of tumor-supportive signaling pathways. The preservation of synergistic activity in 3D tumor spheroids supports the potential preclinical relevance of this combination. However, these findings are based on transcriptional and phenotypic analyses and should be interpreted as hypothesis-generating, requiring further validation through protein-level and in vivo studies before translational application. Full article

Effectively activating protective CD8⁺ T cell immunity specifically against cancer antigens is an important pathway to prevent the growth of various types of cancers. A major obstacle in this approach is variations in cancer antigens among patients. A valuable material to overcome the antigen variation among cancer patients is the use of each individual’s own cancer cells for immunization. In colorectal cancer (CRC), approximately one-third of the patients who receive curative surgical resection have a recurrence of cancer. Therefore, the use of surgically resected CRC for immunotherapy to specifically activate the protective CD8⁺ T cells against their own cancer cells is a valuable approach to prevent the recurrence of cancer. However, since cancer-specific antigens are often not strongly immunogenic, a potent immunostimulant is required as an adjuvant for efficiently facilitating the activation of cancer-specific protective CD8⁺ T cells. We recently identified that a protein molecule, the amino-terminus region of the dense granule protein 6 (GRA6Nt) of Toxoplasma gondii, selectively activates innate expressions of IFN-γ and IL-18 and functions as a powerful adjuvant when used in immunization with nonreplicable (treated with mitomycin C or irradiated) MC38 CRC cells to potently activate the cytotoxic activity and IFN-γ production of CD8⁺ T cells against cancer cells. In addition, immunization using the GRA6Nt protein adjuvant effectively inhibits the growth of identical CRC cells after its challenge implantation, which mimics a recurrence of the surgically resected CRC used for the immunizations. In contrast to the two nucleotide- or deoxynucleotide-based Toll-like receptor agonists currently being used as adjuvants in cancer immunotherapy in clinical settings, GRA6Nt is a protein molecule. Thus, the rGRA6Nt protein adjuvant provides a new pathway in cancer immunotherapy to effectively activate the protective CD8⁺ T cells specific for the individual’s cancer cells to prevent the recurrence of surgically resected CRC in patients. Full article

Chemical monitoring of pollutants and hazardous materials in water supply systems traditionally depends on centralized laboratories, advanced instrumentation, and trained personnel, limiting accessibility and preventing real-time, on-site analysis. This work presents an alternative cost-effective, field-deployable approach that uses genetically engineered bioluminescent bioreporters, encapsulated in self-sufficient alginate capsules and integrated with an optoelectronic detection circuit, to detect and quantify target materials in water. We have developed a scalable single-channel prototype featuring four sensing tracks—two for sample measurement, one for clean water, and one for a standard reference solution. The latter employs the standard ratio (SR) method to ensure robust quantification, compensating for batch variability and environmental effects. System characterization showed high uniformity across tracks. Validation with nalidixic acid (NA) demonstrated reliable quantitative performance, with a blind test estimation of 5.6 mg/L for a true concentration of 5 mg/L, well within the calibration error range. Additional sensitivity testing confirmed detection of mitomycin C (MMC) at concentrations as low as 50 µg/L. Overall, the results highlight the potential of bacterial chemical sensing as a practical and scalable tool for real-time, in situ water quality monitoring networks. Full article

Background/Objectives: This study aims to depict trends in Endoscopic Dacryocystorhinostomy research in Asian countries. Methods: A bibliometric analysis was performed in April 2024 utilizing the SCOPUS database. The keywords “Endoscopic Dacryocystorhinostomy” OR “Endo-DCR” OR “Endonasal Endoscopic Dacryocystorhinostomy” were used. Data cleaning was then performed. Microsoft Excel and Vosviewer software were used to analyze data. Results: 730 articles and 37 keywords were yielded after exclusion. Our analysis revealed a notable increase in Endoscopic Dacrycocystorhinostomy publications from the early 2000s, with a significant surge post-2010. India and China were the leading contributors to Endoscopic Dacryocystorhinostomy research in Asia. Keywords such as “endoscopy”, “silicone tube”, and “epiphora” were commonly used. However, keywords like “mitomycin C”, “mucosal flap” and “success rate” were infrequently found. Conclusions: The emergence of Endoscopic Dacryocystorhinostomy publications witnessed a notable increase from 1972 to 2023 with most studies affiliated to India and China. Certain keywords such as “mitomycin C”, “mucosal flap”, “revision”, “laser”, “drill”, and “success rate” were infrequently used. Full article