Search Results (1,801)

The absent decline in cancer mortality rates is primarily due to moderate therapeutic efficacy and intrinsic or acquired tumor cell resistance toward treatments. Combining different oncology treatments increases therapy success and decreases the chance of refractory tumor cells. Therefore, combination cancer treatments are the principal paradigm of 21st-century oncology. Physical modalities such as radiotherapy have a long-standing tradition in such combination treatments. In the last decade, another physical principle emerged as a promising anticancer agent: cold gas plasma. This partially ionized gas, operated at about body temperature, emits multiple bioactive components, including reactive oxygen and nitrogen species (ROS/RNS). This technology’s multi-ROS/RNS nature cannot be phenocopied by other means, and it capitalizes on the vulnerability of tumor cells within metabolic and redox signaling pathways. Many cancer models exposed to mono or combination gas plasma treatments have shown favorable results, and first cancer patients have benefited from cold gas plasma therapy. The main findings and proposed mechanisms of action are summarized. Considering the specific application modes, this review identifies promising gas plasma combination therapies within guideline-directed treatment schemes for several tumor entities. In conclusion, gas plasmas may become a potential (neo)adjuvant therapy to existing treatment modalities to help improve the efficacy of oncological treatments. Full article

Background: Endometrial cancer (EC) is the most common gynecologic malignancy in developed countries. Despite advances in diagnosis and treatment, recurrence and mortality remain significant concerns. The neutrophil-to-lymphocyte ratio (NLR), a marker of systemic inflammation, has shown prognostic value in several malignancies, but its utility in EC remains underexplored. Objective: To evaluate the prognostic significance of the preoperative NLR in patients with endometrial cancer undergoing primary surgical treatment. Methods: We conducted a retrospective cohort study including 398 patients with histologically confirmed endometrial adenocarcinoma surgically treated at a tertiary cancer center. Preoperative complete blood counts were used to calculate NLR, and a cutoff value of 2.27 was determined through Receiver Operating Characteristic (ROC) analysis. Survival outcomes were assessed using Kaplan–Meier analysis and Cox proportional hazards modeling. Results: Patients with NLR ≥ 2.27 had significantly reduced median overall survival (OS) compared to those with NLR < 2.27 (72.3 vs. 92.8 months, p = 0.008). In multivariate analysis, elevated NLR remained an independent predictor of poorer OS (HR = 1.87; 95% CI: 1.156–3.017; p = 0.011), alongside age ≥ 64 years, lymphovascular space invasion (LVSI), lymph node involvement, and distant metastases. ROC analysis yielded an Area Under the Curve (AUC) of 0.646 for NLR. Notably, vaginal brachytherapy was associated with improved survival (HR = 0.53; p = 0.026), while other adjuvant therapies were not independently significant. Conclusions: Preoperative NLR is an accessible, independent prognostic biomarker in endometrial cancer and may serve as a surrogate indicator of tumor-promoting inflammation and immune dysregulation. Its integration into preoperative assessment could enhance risk stratification and guide personalized treatment strategies. However, findings should be interpreted in light of the study’s retrospective design, single-center setting, and lack of molecular classification data. Prospective validation is warranted to confirm its clinical utility. Full article

Purpose of Review: In approximately 10–15% of patients with prostate cancer (PCa), pathological lymph node metastases (pN1) are detected at radical prostatectomy (RP). The aim of this review is to describe the various treatment options for pN1 patients, with a focus on the most recent evidence reported in the literature. Evidence Synthesis: Due to the lack of prospective studies, several retrospective analyses were conducted according to different types of treatment. Most common strategies are represented by observation plus early salvage radiotherapy (RT) in case of PSA rising, adjuvant androgen deprivation therapy (ADT) alone, or adjuvant RT with or without ADT. Patients with pN1 disease and favorable disease characteristics (lower T stage and ISUP ≤ 2 at RP, <3 metastatic nodes at pathology) have a similar overall mortality risk if observed with PSA testing and eventual use of early salvage RT compared to patients directly treated with adjuvant RT with or without ADT. While conflicting results in terms of survival benefit were reported for the use of adjuvant ADT only, several studies showed an overall survival benefit in patients with pN1 disease treated with adjuvant RT when high-risk features (such as an increasing number of positive nodes, ISUP > 3) were detected at RP. Lastly, few studies analyzed the rate of adverse events following adjuvant ADT or RT, leaving the issue of treatment-related side effects still open. Summary: There is no clearly established standard of care for men with pN1 PCa, and disease characteristics should guide the choice of optimal post-operative management for these patients. Prospective data and clinical trials are clearly needed to define the most effective therapeutic strategy. Full article

Background: Vulvar leiomyosarcoma (VLMS) is a rare and aggressive soft tissue malignancy arising from smooth muscle cells, comprising less than 3% of vulvar cancers. Its clinical resemblance to benign vulvar lesions often leads to delayed diagnosis. Despite surgical resection and adjuvant therapy, VLMS is associated with high recurrence rates and a poor prognosis, and due to its rarity, there is no standardized management or surveillance protocol. Case Report: We present a case of high-grade VLMS in a postmenopausal woman, initially diagnosed in 2020 and managed with surgical excision and adjuvant radiotherapy. The primary tumor was a 10 cm solid, lobulated mass involving the mons pubis, with histology confirming high-grade leiomyosarcoma based on marked cellular atypia, high mitotic activity, and smooth muscle differentiation. Immunohistochemistry was positive for SMA, vimentin, and CD34, and negative for S100 and MyoD1. Five years later, the patient developed a local recurrence with an enlarged inguinal lymph node. She underwent complete tumor resection and bilateral inguinal lymphadenectomy. Histology of the recurrent lesion mirrored the initial findings, with no lymph node metastases. This case highlights the aggressive nature and potential for late recurrence in vulvar leiomyosarcoma, underscoring the importance of long-term surveillance. Conclusions: High-grade VLMS is a rare malignancy with a high recurrence risk. This case highlights the importance of early diagnosis, radical surgical treatment, and long-term surveillance. Although recurrence occurred five years after the initial treatment, timely surgical intervention led to a favorable postoperative course. Multidisciplinary management and individualized follow-up strategies remain key to improving outcomes in these rare gynecologic sarcomas. Full article

Perioperative/neoadjuvant chemo-immunotherapy is a standard treatment for patients with resectable non-small cell lung cancer (NSCLC). However, several key clinical questions remain unresolved, including the monitoring of tumor response during neoadjuvant treatment, detection of residual disease after neoadjuvant treatment or after surgery, stratification of recurrence risk, and earlier detection of disease recurrence. Circulating tumor DNA (ctDNA) has emerged as a promising biomarker to address these challenges. Data from several recent clinical trials of perioperative/neoadjuvant chemo-immunotherapy demonstrated that ctDNA clearance before surgery was associated with higher rates of major pathological response. Additionally, landmark ctDNA positivity after surgery identified patients at high risk of disease recurrence, and longitudinal ctDNA monitoring enabled earlier detection of recurrence compared with radiographic surveillance. Several ongoing trials are incorporating ctDNA as a biomarker to guide treatment decisions, including optimizing the duration of neoadjuvant therapy, evaluating the need for surgery, and tailoring adjuvant strategies. These trials, together with further development of ctDNA detection technologies, will clarify the role of ctDNA analysis in refining perioperative treatment strategies and may ultimately enable individualized care in patients with resectable NSCLC. In this review, we discuss the current research data on ctDNA analysis in NSCLC in this era of perioperative chemo-immunotherapy. Full article

Adenoma-like adenocarcinoma (ALAC) of the colon is a recently recognized histological subtype of colorectal adenocarcinoma, characterized by a villous architecture, low-grade cytologic atypia, and deceptive bland morphology despite its invasive potential, which can mimic non-invasive adenomas, leading to underdiagnosis in limited biopsy samples. Herein, we report the case of an 81-year-old male presenting with right-upper-quadrant pain that was found to have a hepatic abscess and a 4 cm villous lesion in the ascending colon. Histopathological examination of the right hemicolectomy specimen revealed a villous adenocarcinoma with invasion of the muscularis propria, consistent with adenoma-like adenocarcinoma. Isolated loss of PMS2 indicated a mismatch repair deficiency. However, adjuvant therapy was not indicated. The patient remained recurrence-free for three years, until he died from unrelated causes in the context of progressive frailty and comorbidities, with no evidence of cancer progression. This case highlights the diagnostic challenges posed by ALAC and underscores the importance of recognizing its distinct morphological features. Awareness of this entity is essential to avoid misclassification and ensure adequate treatment, especially given its typically favorable prognosis with low metastatic potential. Full article

This study aimed to evaluate the effects of dextromethorphan (DX), alone and in combination with gemcitabine (GEM), on cell viability, apoptosis, and epithelial–mesenchymal transition (EMT) markers in PANC-1 human pancreatic cancer cells. PANC-1 human pancreatic cancer cells were cultured and treated with varying concentrations of dextromethorphan (DX), gemcitabine (GEM), and 5-fluorouracil (5-FU), both as monotherapies and in combination. Cytotoxic effects were assessed using the MTT assay, and IC₅₀ values were calculated at 24, 48, and 72 h. Apoptotic responses were evaluated using Annexin V-FITC/PI staining followed by flow cytometry. Protein expression levels of Bax, Bcl-2, and Vimentin were determined via immunocytochemistry, while EMT markers (E-cadherin, N-cadherin, Vimentin) were analyzed using flow cytometry. Relative mRNA expression of apoptotic and EMT-related genes was quantified by qRT-PCR. DX exhibited time- and dose-dependent cytotoxicity in PANC-1 cells, with IC₅₀ values of 280.4 µM at 24 h, 163.2 µM at 48 h, and 105.6 µM at 72 h. For GEM, the 72 h IC₅₀ was 57.53 µM. The combination of DX 50 µM + GEM 12.5 µM resulted in significantly lower cell viability (24.93 ± 3.12%) compared to GEM 25 µM (35.33 ± 5.22%) and DX 100 µM (51.40 ± 3.10%) (p < 0.001). Flow cytometry revealed significant increases in early (21.83 ± 1.32%) and late apoptotic cells (32.20 ± 0.84%) in the combination group, with a corresponding reduction in viable cells compared to control (24.93 ± 3.12% vs. 89.53 ± 0.97%, p < 0.001). Immunocytochemical analysis showed increased Bax-positive cell count (62.0 cells/unit area), and decreased Bcl-2 (19.0) and Vimentin (28.0) levels in the combination group compared to control (Bax: 15.0, Bcl-2: 60.0, Vimentin: 70.0) (p < 0.001). Flow cytometry for EMT markers demonstrated increased E-cadherin (83.84 ± 0.65%) and decreased Vimentin (71.04 ± 1.17%) and N-cadherin (30.47 ± 0.72%) expression in the DX + GEM group compared to EMT control (E-cadherin: 68.97 ± 1.43%, Vimentin: 91.00 ± 0.75%, N-cadherin: 62.47 ± 1.13%) (p < 0.001). qRT-PCR supported these findings with increased Bax (2.1-fold), E-cadherin (2.0-fold), and reduced Bcl-2 (0.3-fold) and XIAP (0.6-fold) in the combination group (p < 0.05). Dextromethorphan, particularly in combination with gemcitabine, appears to enhance apoptosis and suppress EMT-associated marker expression in PANC-1 cells, supporting its potential as an adjuvant agent in pancreatic cancer therapy. Full article

Aromatase inhibitors (AIs), with or without gonadotropin-releasing hormone analogs, are the cornerstone of adjuvant endocrine therapy for women with hormone receptor-positive early-stage breast cancer, offering significant reductions in recurrence risk and improving long-term survival. Their use is frequently accompanied by treatment-related toxicities that can adversely affect patients’ quality of life (QoL) and adherence to therapy. Commonly reported side effects include vasomotor symptoms, such as hot flashes; musculoskeletal disorders, such as arthralgia and myalgia; mood disorders; and genitourinary discomfort, such as vaginal dryness and dyspareunia. Additionally, AIs are associated with a heightened risk of bone loss, leading to osteoporosis and fractures, and may have implications for cardiovascular health. Effective management of these adverse events is pivotal in maintaining treatment adherence and preserving QoL. Evidence-based strategies to address these toxicities include pharmacological interventions, such as analgesics for joint pain, bisphosphonates or denosumab for bone health, and hormonal or non-hormonal approaches for vasomotor and genitourinary symptoms. Non-pharmacological measures, including physical activity, dietary adjustments, and complementary therapies, can also help mitigate symptoms. This review examines the broad spectrum of AI-associated toxicities, discusses their clinical implications, and provides an overview of evidence-based management strategies. These insights aim to support clinicians in optimizing patient care while minimizing the toxicities of therapy. Full article

Surgical site infections (SSIs) occur in 10–15% of patients and are linked to up to 29% of delays in starting adjuvant treatment. This study assessed the association between SSIs in patients with ovarian and uterine cancer and their impact on time to adjuvant therapy and oncologic outcomes. Patients who underwent surgery from 1 January 2015 to 30 September 2017 were included, using institutional National Surgical Quality Improvement Program (NSQIP) data and chart reviews. Among 371 patients (median follow-up 4.1 years), 243 (65.5%) received adjuvant treatment. The median time to start was 39 days for chemotherapy, 61 days for radiotherapy, and 42 days for combined therapy (p < 0.001). Patients with ovarian cancer began treatment sooner than those with uterine cancer (39 vs. 52 days, p < 0.001), but no significant difference was observed between those with or without SSIs. In 238 patients with uterine cancer, those with SSIs had a twofold higher recurrence risk (HR 1.97, p = 0.022) and over threefold lower overall survival (HR 3.45, p = 0.018). Multivariable analysis showed that surgical route and disease stage were independent predictors; SSI was not an independent factor. No survival difference related to SSIs was found in patients with ovarian cancer. Further research is needed to clarify the impact of SSIs on treatment timing and recurrence. Full article

Identifying effective adjuvants to prevent and alleviate the adverse effects of chemotherapy remains a critical challenge in cancer therapy. This study investigated the protective effects of longan polysaccharide (LP) against cyclophosphamide-induced immunosuppression and oxidative stress in mice. Our findings revealed that LP administration significantly improved systemic immune function, as evidenced by marked increases in serum immunoglobulin levels (IgG2a: 1.82-fold, IgG2b: 1.46-fold, IgM: 1.26-fold, and IgG1: 1.22-fold) and key cytokines (IL-10: 1.53-fold, IL-12: 1.22-fold, and IFN-γ: 1.20-fold), accompanied by substantial reductions in pro-inflammatory mediators (TGF-β1: 28.72% decrease and IL-21: 36.28% decrease). Concurrently, LP restored oxidative balance by increasing SOD, GSH, and NO levels in multiple organs (liver, kidneys, and small intestine) and serum. Mechanistic studies using an in vitro Caco-2/RAW264.7 coculture system revealed that four purified LP fractions (LPIa-LPIVa) effectively suppressed NF-κB pathway activation through downregulation of TLR4 expression, reduction of the p-IκB-α/IκB-α ratio, and inhibition of nuclear NF-κB translocation. These molecular effects correlated with decreased production of inflammatory mediators (TNF-α, IL-6, IL-8, iNOS, and NO). Collectively, these findings provide compelling evidence that LP possesses dual immunomodulatory and antioxidant capabilities, highlighting its potential as a natural adjuvant for alleviating chemotherapy-induced side effects. Full article

Honokiol (HON) and magnolol (MAG), structural isomers from Magnolia officinalis, exhibit notable anticancer activity, particularly against head and neck squamous cell carcinoma (HNSCC). However, due to their high lipophilicity, their intravenous administration is challenging. This study aimed to develop HON- and MAG-loaded intravenous (IV) nanoemulsions using commercial lipid preparations with varying fatty acid compositions. The formulations were physicochemically characterized and evaluated in vitro using FaDu and SCC-040 HNSCC cell lines. HON and MAG were sterilized via ionizing radiation at doses of 25, 100, and 400 kGy. Their suitability for IV use was assessed through PXRD, DSC, TGA, EPR, FT-IR, NMR, and HPLC analyses. All formulations met safety criteria for IV administration, with mean droplet diameters below 241 nm and encapsulation efficiencies exceeding 95%. They significantly reduced cancer cell viability, with a synergistic effect observed in combined HON and MAG formulations compared to single-compound nanoemulsions. Clinoleic-based formulations showed enhanced anticancer efficacy, likely due to the pro-apoptotic properties of oleic acid. Notably, radiation sterilization at the standard 25 kGy dose preserved the thermal, crystalline, and structural stability of HON and MAG, whereas higher doses (400 kGy) induced degradation. Although free radicals were detected via EPR, their transient nature and rapid decay confirmed the method’s safety. HON/MAG-loaded nanoemulsions exhibited strong anticancer potential, while radiation sterilization at 25 kGy ensured sterility without compromising stability. These findings provide a preliminary in vitro basis for future in vivo studies investigating HON and MAG as potential adjuvant therapies for HNSCC. Full article

Melanoma is a type of skin cancer with high lethality and increasing incidence. Current treatments typically involve surgery as the first step, followed by adjuvant treatments, which are necessary in most cases. These adjuvant treatments may include radiotherapy, phototherapy, chemotherapy, immunotherapy, and combined therapies. However, patients with melanoma still face great difficulties, such as the inefficiency of therapies and serious side effects, in addition to uncomfortable scars. Most of these problems are related to limitations of antitumor therapies, such as the low bioavailability of drugs, degradation in biological fluids, rapid clearance, difficulty in reaching the tumors, the low capacity for accumulation and infiltration in tumor cells, toxicity to healthy cells, and systemic action. Thus, antitumor therapy for melanoma remains a challenge. In this line, nanotechnology has brought new perspectives and has been the subject of intensive research on the use of nanoparticles (liposomes, lipid nanoparticles, polymeric nanoparticles, inorganic nanoparticles, carbon nanotubes, dendrimers, nanogels, and biomimetic nanoparticles, among others) as carriers for the controlled release of drugs and tumor diagnosis. This work outlines the main limitations of current melanoma therapies and explores how nanoparticle-based drug delivery systems can overcome these challenges, highlighting recent research and clinical developments. Full article

Cucurbitacin B (CuB), a tetracyclic triterpenoid compound isolated from Cucurbitaceae plants, exhibits inhibitory effects on various tumor cells (e.g., liver, gastric, and colorectal cancer cells). Since the 1970s–1980s, cucurbitacin tablets containing CuB have been used as an adjuvant therapy for chronic hepatitis and primary liver cancer. CuB exerts anticancer effects through multiple mechanisms: inducing apoptosis, cell cycle arrest (G2/M or S phase), autophagy, and cytoskeleton disruption; inhibiting migration, invasion, and angiogenesis (via VEGF/FAK/MMP-9 and Wnt/β-catenin pathways); regulating metabolic reprogramming and immune responses; inducing pyroptosis, ferroptosis, and epigenetic changes; and reversing tumor drug resistance. These effects are associated with signaling pathways like JAK/STAT, PI3K/Akt/mTOR, and FOXM1-KIF20A. To improve its application potential, strategies such as structural modification (e.g., NO donor conjugation), combination therapy (with gemcitabine or cisplatin), and nanomaterial-based delivery (e.g., liposomes and exosome-mimicking nanoparticles) have been developed to enhance efficacy, reduce toxicity, and improve bioavailability. CuB shows broad-spectrum anticancer activity, but further research is needed to clarify the mechanisms underlying its cell-specific sensitivity and interactions with the immune system. This review systematically summarizes the physicochemical properties, anticancer mechanisms, and strategies for applying CuB and suggests future research directions, providing references for scientific research and clinical translation. Full article

The optimal sequencing of chemotherapy in locally advanced gastric cancer (LAGC) remains controversial. This study aimed to compare survival outcomes between adjuvant (ACT) and neoadjuvant (NACT) chemotherapy and to identify clinicopathological factors associated with progression-free survival (PFS) and overall survival (OS) in a real-world setting. Methods: We retrospectively analyzed 103 patients with non-metastatic gastric cancer treated between 2014 and 2024. Patients were categorized into ACT (n = 56) and NACT (n = 47) groups. Kaplan–Meier and Cox regression analyses were used to assess survival outcomes and prognostic factors. Results: The NACT group was younger and had more proximal tumors. Median OS was 48.7 months in the ACT group versus 17.7 months in the NACT group (p = 0.048). Median PFS was not reached in the ACT group and was 15.6 months in the NACT group (p = 0.008). Negative surgical margin status was independently associated with improved survival, whereas age was an independent negative prognostic factor for OS. No significant associations were found between OS or PFS and histologic subtype, lymphovascular invasion, perineural invasion, gender, D2 dissection, or type of surgery. Notably, 21% of NACT patients did not proceed to surgery due to progression, treatment intolerance, or refusal. Conclusion: Although ACT was associated with longer PFS and OS in this cohort, these differences are most likely explained by baseline imbalances, patient selection factors, and survivorship bias rather than the timing of chemotherapy itself. These findings highlight the importance of careful patient selection for NACT and underscore the need for prospective, randomized studies to define optimal sequencing strategies in LAGC. Our study contributes descriptive, real-world data rather than definitive evidence of treatment superiority. Full article

Background/Objectives: Colorectal cancer (CRC) remains a major health challenge due to its high incidence and resistance to conventional therapies. Natural compounds have gained attention as potential adjuvant treatments. The study assesses whether combining Allium sativum and Vitis vinifera [rich in oligomeric proanthocyanidins condensed (OPCs)] extracts enhances cell viability reduction and migration inhibition. Methods: Human colorectal cancer cell lines (Caco-2 and HT-29) were treated with increasing concentrations of both extracts individually and in combination. Cell viability was assessed using MTT assays, while migration was evaluated through scratch wound assays. Synergistic effects were analyzed using Combenefit software. Results: Both extracts significantly reduced cell viability in a dose- and time-dependent manner. The combination of both extracts led to an enhanced reduction in cell viability, with a transient synergistic effect observed at 24 h in HT-29 cells. Regarding migration, OPCs showed a transient anti-migratory effect at 6 h in HT-29 cells, but no significant impact was observed in Caco-2 cells or at later time points. Conclusions: These findings suggest that Allium sativum and Vitis vinifera extracts have potential as complementary treatments for colorectal cancer, mainly through their effect on cell viability. This study opens a field of research on the possible therapeutic effects of natural extracts. Full article