Current Issue : July-September Volume : 2025 Issue Number : 3 Articles : 5 Articles
Background/Objectives: Pancreatic ductal adenocarcinoma (PDA) is one of the most malignant solid cancers. KRAS mutation accounts for over 90% of cases. p21-activated kinases (PAKs) act downstream of KRAS and are involved in tumorigenesis. The inhibition of PAK4 suppresses PDA by stimulating the tumor infiltration of cytotoxic T cells. The major histocompatibility complex class I (MHC I) is a key in presenting antigens to cytotoxic T cells. MHC I degradation via autophagy promotes the immune evasion of pancreatic cancer. We investigated the effect of PAK4 inhibition on MHC I expression and autophagy. Methods: In this study, using proteomic analysis, fluorescence-activated cell sorting (FACS), and immunoblotting, we examined the effect of PAK4 knockout (KO) in human PDA cells on the expression of MHC I and autophagy to identify the mechanism involved in the stimulation of cytotoxic T cells by PAK4 inhibition. Results: We found that PAK4 KO increased MHC I expression in two human PDA cell lines: MiaPaCa-2 and PANC-1. PAK4 KO also increased cancer cell autophagy. However, the inhibition of autophagy by chloroquine (CQ) did not affect the effect of PAK4 KO on apoptosis and cell death. More importantly, the inhibition of autophagy by CQ did not alter the expression of MHC I stimulated by PAK4 KO, indicating that PAK4 KO stimulated MHC I expression via an autophagy-independent pathway. Conclusions: We identified a role of PAK4 in MHC I expression by PDA cells, which is independent of autophagy....
Background/Objectives: The aim of this study is to evaluate the impact of tumor characteristics on lesion conspicuity in contrast-enhanced mammography (CEM) and identify factors associated with different levels of conspicuity. Methods: In this retrospective study, we analyzed 552 patients with breast cancer who underwent CEM. Lesion conspicuity was categorized into three levels: 1 (low), 2 (moderate), and 3 (high). Tumor characteristics included age, histological subtype, hormone receptor status, HER2 status, Ki67 index, tumor grade, and molecular subtype. Univariate and multivariate analyses were conducted to assess associations between lesion conspicuity and these factors. Results: Of the 552 cases, the majority showed mass enhancement (78.1%), followed by non-mass enhancement (NME) (16.8%), and a combination of mass and NME (4.0%). Lesion conspicuity was significantly associated with enhancement type on CEM (p < 0.001). High conspicuity (score 3) was predominantly observed in masses (84.8%) compared to NME (7.6%). Larger tumor dimensions (median 20 mm) were also associated with higher conspicuity (p < 0.001). Molecular subtypes differed significantly in conspicuity, with Luminal A tumors showing lower conspicuity compared to HER2-positive and triplenegative breast cancers (p = 0.025). In multivariate analysis, lesion conspicuity was strongly associated with enhancement type (p < 0.001) and tumor dimensions (p < 0.001), while histological subtype and molecular characteristics had no significant independent impact. Conclusions: Lesion conspicuity in CEM is primarily influenced by the type of enhancement and tumor size. Mass-forming lesions, particularly larger ones, are more conspicuous, while NME tends to result in lower conspicuity. These findings suggest that enhancement patterns and tumor dimensions are key factors to consider when interpreting CEM in breast cancer diagnosis....
Introduction: Lobectomy with lymph node dissection is the gold standard treatment for stage IA–IIA Non-Small Cell Lung Cancer (NSCLC). Surgery is responsible for higher early mortality but offers better overall long-term survival. The patient population concerned is often elderly and combines the comorbidities of smoking and age. Several trials have shown good results of stereotactic radiotherapy (SABR) in terms of local control and tolerance in elderly subjects. Our objective is to study the survival and regional control of patients over 75 years treated by surgery or SABR for localized NSCLC. Materials and Method: We conducted a single-center retrospective study between January 2012 and December 2022 including elderly patients who received surgery or SABR for NSCLC less than 5 cm in size, N0, M0. A cumulative comorbidity index was calculated for each patient, considering severity and impact of treatment. We performed subgroup analyses using CART method to identify factors impacting survival and early death. Results: After propensity score matching, 127 operated patients were matched to 85 patients treated with SABR. Overall survival at 1 and 5 years for the operated patients was 83.87% and 47.30% compared with 88.8% and 31.5% in the radiotherapy group (p = 0.068). We have identified four factors influencing the incidence of early mortality: gender,World Health Organization Performance status (WHO status), Forced Expiratory Volume in 1 s (FEV1), and treatment group. Conclusions: Surgery seems to remain the standard of treatment in terms of overall survival and locoregional recurrence, in a context where SABR nevertheless provides excellent local control and tolerance in the short and long term. In order to improve patient selection, we are proposing for the first time a tool to aid therapeutic decision-making....
Pancreatic neuroendocrine tumors (pNETs) are rare but increasingly prevalent malignancies with varied prognoses and a diverse range of treatment options, including surgery, somatostatin analogues (SSAs), chemotherapy, targeted therapy, and peptide receptor radionuclide therapy (PRRT). This retrospective cohort study analyzed treatment patterns among 189 pNET patients treated between January 2010 and June 2021 at two Canadian cancer centres: the Verspeeten Family Cancer Centre (VFCC), which offers PRRT, and the Ottawa Hospital Cancer Centre (TOHCC), which does not at the time of the study. Data on demographics, tumor characteristics, and treatment modalities were collected, and statistical analyses were conducted using chi-square, Fisher’s exact test, and the Kruskal– Wallis test. Among eligible patients, 53% presented with stage IV disease. Surgical resection was the most common treatment, followed by SSAs, chemotherapy, PRRT, and targeted therapy. Stage IV patients at VFCC were significantly more likely to receive PRRT (60%) compared to TOHCC (6%) and underwent more PRRT cycles, with a higher prevalence of well-differentiated tumors observed at VFCC.With these differences it was clear that the non-PRRT centre was unable to provide patients with the same level of PRRT access during the study period compared to patients seen at the PRRT site. The findings underscore the critical role of PRRT availability in influencing treatment patterns and highlight the need for equitable access to specialized therapies across Canada to optimize outcomes for pNET patients....
Background: Male breast cancer (MaBC) is a rare disease and due to its rarity and the lack of specific protocols for its management, treatment algorithms are extrapolated from female breast cancer (FBC). To optimize MaBC treatment, we conceived an umbrella review with the aim of supplying an evidence-based summary of systematic reviews published about this topic in the last twenty years. Methods: This umbrella review was performed according to a predefined protocol (PROSPERO number CRD42024574299). We performed a literature search of the PubMed and Cochrane Libraries databases and we considered systematic reviews on MaBC treatment published from 2004 to 2024. We evaluated relevant treatments in the management of MaBC, including surgery, radiotherapy, and systemic treatments. We conducted the quality assessment according to A MeaSurement Tool to Assess systematic Reviews version 2 (AMSTAR-2), and the description of the main findings of eligible articles. Results: Seven systematic reviews were selected and the main findings were compiled. Breast-conserving surgery is a reasonable treatment approach and, in selected cases, equivalent in terms of safety and survival outcomes compared to mastectomy. Sentinel lymph node biopsy represents a successful surgical practice with similar accuracy compared to female cases. Adjuvant radiotherapy improves overall survival in MaBC patients following partial mastectomy and after radical mastectomy, in case of involved nodes. Finally, Tamoxifen is associated with an improvement of survival outcomes; aromatase inhibitor and gonadotrophin-releasing hormone should be used only in case of contraindications to tamoxifen. Conclusions: Further research and improved guidelines for MaBC treatment should consider these evidence-based data....
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