Search Results (1,254)

Background: Breast cancer is the most prevalent malignancy among women globally. In Romania, it is the most frequent form of cancer affecting women, with approximately 12,000 new cases diagnosed annually, and the second most common cause of cancer-related mortality, second only to lung cancer. Methods: This study looked at 79 breast cancer patients from Oltenia, concentrating on epidemiology, histology, diagnostic features, and treatments. Patients were chosen based on inclusion criteria such as histopathologically verified diagnosis, availability of clinical and treatment data, and follow-up information. The analyzed biological material consisted of tissue samples taken from the breast parenchyma and axillary lymph nodes. Even though not the primary subject of this paper, all patients underwent immunohistochemical (IHC) evaluation both preoperatively and postoperatively. Results: We found invasive ductal carcinoma to be the predominant type, while ductal carcinoma in situ (DCIS) and mixed types were rare. We performed cross-tabulations of metastasis versus nodal status and age versus therapy type; none reached significance (all p > 0.05), suggesting observed differences were likely due to chance. A chi-square test comparing surgical interventions (breast-conserving vs. mastectomy) in patients who did or did not receive chemotherapy showed, χ² = 3.17, p = 0.367, indicating that chemotherapy did not significantly influence surgical choice. Importantly, adjuvant chemotherapy and radiotherapy were used at similar rates across age groups, whereas neoadjuvant hormonal (endocrine) therapy was more common in older patients (but without statistical significance). Conclusions: Finally, we discussed the consequences of individualized care and early detection. Romania’s shockingly low screening rate, which contributes to delayed diagnosis, emphasizes the importance of improved population medical examination and tailored treatment options. Also, the country has one of the lowest rates of mammography uptake in Europe and no systematic population screening program. Full article

Background/Objectives: Gallbladder cancer (GBC) is a lethal malignancy curable only by surgical resection in early stages (Tis, T1, T2). Significant controversy exists regarding the optimal extent of surgery. This review summarizes recent trends and evidence on surgical strategies for Tis, T1, and T2 GBC to guide practice and research. Methods: This narrative review synthesizes recent literature on surgical management of Tis, T1a, T1b, and T2 GBC based on American Joint Committee on Cancer (AJCC) 8th edition staging. It examines simple vs. extended cholecystectomy (simple cholecystectomy (SC) vs. extended/radical cholecystectomy (EC/RC)), the role of lymphadenectomy (LND) and hepatectomy, and minimally invasive surgery (MIS). Results: Simple cholecystectomy is curative for Tis/T1a GBC. For T1b, regional LND is essential for staging/potential benefit, especially examining ≥5–6 nodes. Tumor size is critical; SC alone may suffice for T1b < 1 cm (low lymph node metastasis (LNM) risk), while EC/RC with LND is indicated for ≥1 cm (higher LNM risk). Routine hepatectomy for T1b lacks survival support. For T2 GBC, mandatory regional LND (≥6 nodes) is required for both T2a and T2b substages due to high LNM rates; T2b has higher LNM than T2a. Routine hepatectomy for T2 is debated; evidence suggests no routine benefit for T2a beyond LND, with conflicting findings for T2b. R0 resection is paramount. MIS is feasible for early stages in experienced hands. Conclusions: Management of early GBC is moving towards risk stratification. SC is standard for Tis/T1a. Adequate regional LND is crucial for T1b (especially ≥1 cm) and mandatory for T2 GBC. Routine hepatectomy, particularly for T2b, remains controversial. Tailored surgery prioritizes R0 resection and comprehensive LND, necessitating further standardized research. Full article

Penile cancer is a rare malignancy, with approximately 2100 cases diagnosed annually in the United States. The 5-year overall survival rate varies significantly depending on the node involvement status, at 79% in node-negative disease versus 51% for patients with inguinal metastasis. Inguinal lymph nodes are involved in micrometastatic disease in up to one out of four patients. Early inguinal lymph node dissection (ILND) has been shown to provide a survival advantage, which is why many patients undergo inguinal lymph node dissection for diagnostic and therapeutic purposes. Unfortunately, ILND is associated with high morbidity rates, which have led to potential overtreatment and decreased quality of life in the penile cancer population. Several advancements have been made to mitigate these challenges, such as dynamic sentinel node dissection, modifications to the technique or surgical templates, the introduction of minimally invasive procedures, and changes to the postoperative pathway. This manuscript examines the evolution in managing the inguinal lymph nodes in penile cancer, its associated complications, and effective strategies for their prevention and management. Full article

Background: Patients with resected stage IIB and IIC melanoma are at high risk of recurrence and distant metastasis, despite surgical treatment. The recent emergence of immune checkpoint inhibitors (ICIs) has led to their evaluation in the adjuvant setting for early-stage disease. This review aims to synthesize current evidence regarding adjuvant immunotherapy for stage IIB/IIC melanoma, explore emerging strategies, and highlight key challenges and future directions. Methods: We conducted a comprehensive literature review of randomized clinical trials, observational studies, and relevant mechanistic and biomarker research on adjuvant therapy in stage IIB/IIC melanoma. Particular focus was placed on pivotal trials evaluating PD-1 inhibitors (KEYNOTE-716 and CheckMate 76K), novel vaccine and targeted therapy trials, mechanisms of resistance, immune-related toxicity, and biomarker development. Results: KEYNOTE-716 and CheckMate 76K demonstrated significant improvements in recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) with pembrolizumab and nivolumab, respectively, compared to placebo. However, no definitive overall survival benefit has yet been shown. Adjuvant immunotherapy is linked to immune-related adverse events, including permanent endocrinopathies. Emerging personalized approaches, such as circulating tumor DNA monitoring and gene expression profiling, may enhance patient selection, but remain investigational. Conclusions: Adjuvant PD-1 blockade offers clear RFS benefits in high-risk stage II melanoma, but optimal patient selection remains challenging, due to uncertain overall survival benefit and toxicity concerns. Future trials should integrate biomarker-driven approaches to refine therapeutic decisions and minimize overtreatment. Full article

Colorectal cancer (CRC) is not only the third most common cancer worldwide, with 1.1 million new cases per year; it is also the second leading cause of cancer death. However, mortality has decreased since 2012 due to early detection programs and better therapeutic approaches. While many patients are diagnosed at an early stage, there is up to 50% relapse after optimal initial treatment. Therefore, it is crucial to explore the mechanism underlying the development of recurrences and metastasis. It is known that tumors release dormant cells that escape chemotherapy and nest in a target organ without proliferating. Under certain circumstances that are not yet entirely clear, they can be activated and metastasize. Therefore, the objective of this work is to explore the detailed mechanisms of dormancy, including early detection of recurrence and therapeutic approaches for the treatment of CRC. The specific objectives are to determine biomarkers that may be useful in identifying dormant cells to detect minimal residual disease (MRD) after surgery and predicting disease progression, as well as evaluating biomarkers that are susceptible to therapeutic intervention. Full article

Background: Epidermal growth factor receptor (EGFR) mutations are presented in approximately 50% of East Asian populations with advanced non-small cell lung cancer (NSCLC). While EGFR-tyrosine kinase inhibitors (TKIs) are the standard treatment, patient outcomes are also influenced by host-related factors. This study aimed to investigate clinical and radiological factors associated with early mortality and develop a prognostic prediction model in advanced EGFR-mutated NSCLC. Methods: A retrospective cohort was conducted in patients with EGFR-mutated NSCLC treated with first line EGFR-TKIs from January 2012 to October 2022 at Chiang Mai University Hospital. Clinical data and radiologic findings at the initiation of treatment were analyzed. A multivariable flexible parametric survival model was used to determine the predictors of death at 18 months. The predicted survival probabilities at 6, 12, and 18 months were estimated, and the model performance was evaluated. Results: Among 189 patients, 84 (44.4%) died within 18 months. Significant predictors of mortality included body mass index <18.5 or ≥23, bone metastasis, neutrophil-to-lymphocyte ratio ≥ 5, albumin-to-globulin ratio < 1, and mean pulmonary artery diameter ≥ 29 mm. The model demonstrated good performance (Harrell’s C-statistic = 0.72; 95% CI: 0.66–0.78). Based on bootstrap internal validation, the optimism-corrected Harrell’s C-statistic was 0.71 (95% CI: 0.71–0.71), derived from an apparent C-statistic of 0.75 (95% CI: 0.74–0.75) and an estimated optimism of 0.04 (95% CI: 0.03–0.04). Estimated 18-month survival ranged from 87.1% in those without risk factors to 2.1% in those with all predictors. A web-based tool was developed for clinical use. Conclusions: The prognostic model developed from fundamental clinical and radiologic parameters demonstrated promising utility in predicting 18-month mortality in patients with advanced EGFR-mutated NSCLC receiving first-line EGFR-TKI therapy. Full article

Background: Colorectal liver metastasis (CRLM) represents a major clinical challenge in oncology, affecting 25–50% of colorectal cancer patients and significantly impacting survival. While multimodal therapies—including surgical resection, systemic chemotherapy, and local ablative techniques—have improved outcomes, prognosis remains heterogeneous due to variations in tumor biology, patient factors, and institutional practices. Methods: This review synthesizes current evidence on prognostic factors influencing CRLM management, encompassing clinical (e.g., tumor burden, anatomic distribution, timing of metastases), biological (e.g., CEA levels, inflammatory markers), and molecular (e.g., RAS/BRAF mutations, MSI status, HER2 alterations) determinants. Results: Key findings highlight the critical role of molecular profiling in guiding therapeutic decisions, with RAS/BRAF mutations predicting resistance to anti-EGFR therapies and MSI-H status indicating potential responsiveness to immunotherapy. Emerging tools like circulating tumor DNA (ctDNA) and radiomics offer promise for dynamic risk stratification and early recurrence detection, while the gut microbiome is increasingly recognized as a modulator of treatment response. Conclusions: Despite advancements, challenges persist in standardizing resectability criteria and integrating multidisciplinary approaches. Current guidelines (NCCN, ESMO, ASCO) emphasize personalized strategies but lack granularity in terms of incorporating novel biomarkers. This exhaustive review underscores the imperative for the development of a unified, biomarker-integrated framework to refine CRLM management and improve long-term outcomes. Full article

Bone metastasis remains a significant cause of morbidity and diminished quality of life in patients with advanced breast, prostate, and lung cancers. Emerging research highlights the pivotal role of reversible epigenetic alterations, including DNA methylation, histone modifications, chromatin remodeling complex dysregulation, and non-coding RNA networks, in orchestrating each phase of skeletal colonization. Site-specific promoter hypermethylation of tumor suppressor genes such as HIN-1 and RASSF1A, alongside global DNA hypomethylation that activates metastasis-associated genes, contributes to cancer cell plasticity and facilitates epithelial-to-mesenchymal transition (EMT). Key histone modifiers, including KLF5, EZH2, and the demethylases KDM4/6, regulate osteoclastogenic signaling pathways and the transition between metastatic dormancy and reactivation. Simultaneously, SWI/SNF chromatin remodelers such as BRG1 and BRM reconfigure enhancer–promoter interactions that promote bone tropism. Non-coding RNAs, including miRNAs, lncRNAs, and circRNAs (e.g., miR-34a, NORAD, circIKBKB), circulate via exosomes to modulate the RANKL/OPG axis, thereby conditioning the bone microenvironment and fostering the formation of a pre-metastatic niche. These mechanistic insights have accelerated the development of epigenetic therapies. DNA methyltransferase inhibitors (e.g., decitabine, guadecitabine) have shown promise in attenuating osteoclast differentiation, while histone deacetylase inhibitors display context-dependent effects on tumor progression and bone remodeling. Inhibitors targeting EZH2, BET proteins, and KDM1A are now advancing through early-phase clinical trials, often in combination with bisphosphonates or immune checkpoint inhibitors. Moreover, novel approaches such as CRISPR/dCas9-based epigenome editing and RNA-targeted therapies offer locus-specific reprogramming potential. Together, these advances position epigenetic modulation as a promising axis in precision oncology aimed at interrupting the pathological crosstalk between tumor cells and the bone microenvironment. This review synthesizes current mechanistic understanding, evaluates the therapeutic landscape, and outlines the translational challenges ahead in leveraging epigenetic science to prevent and treat bone metastases. Full article

Background/Objectives: Brain metastasis (BM) is a common and often early manifestation in lung adenocarcinoma (LUAD), yet its tumor microenvironment remains poorly defined at the time of initial diagnosis. This study aims to characterize early immune microenvironmental alterations in synchronous BM using spatial proteomic profiling. Methods: We performed digital spatial proteomic profiling using the NanoString GeoMx platform on formalin-fixed paraffin-embedded tissues from five treatment-naïve LUAD patients in whom BM was the initial presenting lesion. Paired primary lung and brain metastatic samples were analyzed across tumor and stromal compartments using 68 immune- and tumor-related protein markers. Results: Spatial profiling revealed distinct expression patterns between primary tumors and brain metastases. Immune regulatory proteins—including IDO-1, PD-1, PD-L1, STAT3, PTEN, and CD44—were significantly reduced in brain metastases (p < 0.01), whereas pS6, a marker of activation-induced T-cell death, was significantly upregulated (p < 0.01). These alterations were observed in both tumor and stromal regions, suggesting a more immunosuppressive and apoptotic microenvironment in brain lesions. Conclusions: This study provides one of the first spatially resolved proteomic characterizations of synchronous BM at initial LUAD diagnosis. Our findings highlight early immune escape mechanisms and suggest the need for site-specific immunotherapeutic strategies in patients with brain metastasis. Full article

Endometrial cancer is one of the most prevalent gynecologic malignancies in developed countries, with its incidence steadily increasing each year. Early diagnosis is crucial for a favorable prognosis; however, certain patients experience recurrence and distant metastasis after surgery, similar to advanced cancer patients, with limited treatment options. Therefore, effective strategies for early screening, diagnosis, predicting local recurrence, and guiding rapid treatment interventions are essential for improving survival rates and prognosis. Liquid biopsy, a method known for being non-invasive, safe, and effective, has attracted widespread attention for cancer diagnosis and treatment. Although its clinical application in endometrial cancer is less established than in other cancers, research on biomarkers using liquid biopsy in endometrial cancer patients is currently in progress. This review examines the latest advancements in non-invasive biomarkers identified through liquid biopsy and provides a comprehensive overview of their clinical applications in endometrial cancer. Additionally, it discusses the challenges and future prospects of liquid biopsy, offering valuable insights into the diagnosis and personalized treatment of endometrial cancer. Full article

Background: Tongue squamous cell carcinoma (TSCC) is an aggressive oral malignancy characterized by early submucosal invasion and a high risk of cervical lymph node metastasis. Accurate and timely diagnosis is essential, but it remains challenging when relying solely on conventional imaging and histopathology. This systematic review aimed to evaluate studies applying artificial intelligence (AI) in the diagnostic imaging of TSCC. Methods: This review was conducted under PRISMA 2020 guidelines and included studies from January 2020 to December 2024 that utilized AI in TSCC imaging. A total of 13 studies were included, employing AI models such as Convolutional Neural Networks (CNNs), Support Vector Machines (SVMs), and Random Forest (RF). Imaging modalities analyzed included MRI, CT, PET, ultrasound, histopathological whole-slide images (WSI), and endoscopic photographs. Results: Diagnostic performance was generally high, with area under the curve (AUC) values ranging from 0.717 to 0.991, sensitivity from 63.3% to 100%, and specificity from 70.0% to 96.7%. Several models demonstrated superior performance compared to expert clinicians, particularly in delineating tumor margins and estimating the depth of invasion (DOI). However, only one study conducted external validation, and most exhibited moderate risk of bias in patient selection or index test interpretation. Conclusions: AI-based diagnostic tools hold strong potential for enhancing TSCC detection, but future research must address external validation, standardization, and clinical integration to ensure their reliable and widespread adoption. Full article

Early prediction of lymph node metastasis (LNM) following neoadjuvant therapy (NAT) is crucial for timely treatment optimization in esophageal squamous cell carcinoma (ESCC). This study developed and validated a computed tomography-based radiomic model for predicting pathologically confirmed LNM status at the time of surgery in ESCC patients after NAT. A total of 469 ESCC patients from Sun Yat-sen University Cancer Center were retrospectively enrolled and randomized into a training cohort (n = 328) and a test cohort (n = 141). Three signatures were constructed: the tumor-habitat-based signature (Habitat_Rad), derived from radiomic features of three tumor subregions identified via K-means clustering; the multiple instance learning-based signature (MIL_Rad), combining features from 2.5D deep learning models; and the clinicoradiological signature (Clinic), developed through multivariate logistic regression. A combined radiomic nomogram integrating these signatures outperformed the individual models, achieving areas under the curve (AUCs) of 0.929 (95% CI, 0.901–0.957) and 0.852 (95% CI, 0.778–0.925) in the training and test cohorts, respectively. The decision curve analysis confirmed a high net clinical benefit, highlighting the nomogram’s potential for accurate LNM prediction after NAT and guiding individualized therapy. Full article

Background: Lysosomal-associated membrane protein 1 (LAMP1), typically localized to the lysosomal membrane, is increasingly implicated as a marker of cancer aggressiveness and metastasis when expressed on the cell surface. This study aimed to develop a LAMP1-targeted antibody-based PET tracer and assess its efficacy in mouse models of human breast and colon adenocarcinoma. Methods: To determine the source of LAMP1 expression, we utilized human single-cell RNA sequencing and spatial transcriptomics, complemented by in-house flow cytometry on xenografted mouse models. Tissue microarrays of multiple epithelial cancers and normal tissue were stained for LAMP-1, and staining was quantified. An anti-LAMP1 monoclonal antibody was conjugated with desferrioxamine (DFO) and labeled with zirconium-89 (⁸⁹Zr). Human triple-negative breast cancer (MDA-MB-231) and colon cancer (Caco-2) cell lines were implanted in nude mice. PET/CT imaging was conducted at 24, 72, and 168 h post-intravenous injection of ⁸⁹Zr-DFO-anti-LAMP1 and ⁸⁹Zr-DFO-IgG (negative control), followed by organ-specific biodistribution analyses at the final imaging time point. Results: Integrated single-cell and spatial RNA sequencing demonstrated that LAMP1 expression was localized to myeloid-derived suppressor cells (MDSCs) and cancer-associated fibroblasts (CAFs) in addition to the cancer cells. Tissue microarray showed significantly higher staining for LAMP-1 in tumor tissue compared to normal tissue (3986 ± 2635 vs. 1299 ± 1291, p < 0.001). Additionally, xenograft models showed a significantly higher contribution of cancer cells than the immune cells to cell surface LAMP1 expression. In vivo, PET imaging with ⁸⁹Zr-DFO-anti-LAMP1 PET/CT revealed detectable tumor uptake as early as 24 h post-injection. The ⁸⁹Zr-DFO-anti-LAMP1 tracer demonstrated significantly higher uptake than the control ⁸⁹Zr-DFO-IgG in both models across all time points (MDA-MB-231 SUV_max at 168 h: 12.9 ± 5.7 vs. 4.4 ± 2.4, p = 0.003; Caco-2 SUV_max at 168 h: 8.53 ± 3.03 vs. 3.38 ± 1.25, p < 0.01). Conclusions: Imaging of cell surface LAMP-1 in breast and colon adenocarcinoma is feasible by immuno-PET. LAMP-1 imaging can be expanded to adenocarcinomas of other origins, such as prostate and pancreas. Full article

Breast cancer (BC) is a neoplasm characterized by high heterogeneity and is influenced by intrinsic molecular subtypes and clinical stage, aspects that remain underexplored in the Colombian population. This study aimed to characterize metabolic alterations associated with subtypes and disease progression in a group of newly diagnosed, treatment-naive Colombian women using an untargeted metabolomics approach. To improve metabolite coverage, samples were analyzed using LC-QTOF-MS and GC-QTOF-MS, along with amino acid profiling. The Luminal B subtype exhibited elevated levels of long-chain acylcarnitines and higher free fatty acid concentrations than the other subtypes. It also presented elevated levels of carbohydrates and essential glycolytic intermediates, suggesting that this subtype may adopt a hybrid metabolic phenotype characterized by increased glycolytic flux as well as enhanced fatty acid catabolism. Tumor, Node, and Metastasis (TNM) staging analysis revealed progressive metabolic reprogramming of BC. In advanced stages, a sustained increase in phosphatidylcholines and a decrease in lysophosphatidylcholines were observed, reflecting lipid alterations associated with key roles in tumor progression. In early stages (I-II), plasma metabolites with high discriminatory power were identified, such as glutamic acid, ribose, and glycerol, which are associated with dysfunctions in energy and carbohydrate metabolism. These results highlight metabolomics as a promising tool for the early diagnosis, clinical follow-up, and molecular characterization of BC. Full article

Early diagnosis of lung cancer is crucial for improving patient prognosis. In this study, we developed a diagnostic model for lung cancer based on serum proteomic data from the GSE168198 dataset using four machine learning algorithms (nnet, glmnet, svm, and XGBoost). The model’s performance was validated on datasets that included normal controls, disease controls, and lung cancer data containing both. Furthermore, the model’s diagnostic capability was further validated on an independent external dataset. Our analysis identified SLC16A4 as a key protein in the model, which was significantly downregulated in lung cancer serum samples compared to normal controls. The expression of SLC16A4 was closely associated with clinical pathological features such as gender, tumor stage, lymph node metastasis, and smoking history. Functional assays revealed that overexpression of SLC16A4 significantly inhibited lung cancer cell proliferation and induced cellular senescence, suggesting its potential role in lung cancer development. Additionally, correlation analyses showed that SLC16A4 expression was linked to immune cell infiltration and the expression of immune checkpoint genes, indicating its potential involvement in immune escape mechanisms. Based on multi-omics data from the TCGA database, we further discovered that the low expression of SLC16A4 in lung cancer may be regulated by DNA copy number variations and DNA methylation. In conclusion, this study not only established an efficient diagnostic model for lung cancer but also identified SLC16A4 as a promising biomarker with potential applications in early diagnosis and immunotherapy. Full article