Cancers最新文献

Background/Objectives: Early and aggressive metastasis is a major feature of pancreatic ductal adenocarcinoma. Understanding the processes underlying metastasis is crucial for making a difference to disease outcome. Towards these ends, we looked in a comprehensive manner for genes that are metastasis-specific. Methods: A genome-wide CRISPR-Cas9 gene knockout screen with 259,900 single guide RNA constructs was performed on pancreatic cancer cell lines with very high or very low metastatic capacity, respectively. Functional aspects of some of the identified genes were analysed in vitro. The injection of tumour cells with or without a gene knockout into mice was used to confirm the effect on metastasis. Results: The knockout of 590 genes-and, with higher analysis stringency, 67 genes-affected the viability of metastatic cells substantially, while these genes were not vital to non-metastasizing cells. Further evaluations identified different molecular processes related to this observation. One of the genes was MYBL2, encoding for a well-known transcription factor involved in the regulation of cell survival, proliferation, and differentiation in cancer tissues. In our metastasis-focussed study, no novel functional activity was detected for MYBL2, however. Instead, a metastasis-specific transformation of its genetic interaction with FOXM1 was observed. The interaction was synergistic in cells of low metastatic capacity, while there was a strong switch to a buffering mode in metastatic cells. In vivo analyses confirmed the strong effect of MYBL2 on metastasis. Conclusions: The genes found to be critical for the viability of metastatic cells form a basis for further investigations of the processes responsible for triggering and driving metastasis. As shown for MYBL2, unexpected processes of regulating metastasis might also be involved.

Objectives: This retrospective observational study investigated to determine whether surgery or chemoradiation therapy after induction chemotherapy leads to better swallow function for oropharyngeal cancer patients. Methods: We documented the treatment paths and results of 267 patients with oropharyngeal squamous cell cancer (OPSCC). By quantifying nasogastric (NG) tube usage, surgery after induction chemotherapy (IC-surgery), and chemoradiation therapy after induction chemotherapy (IC-CRT) could be compared to determine the effectiveness of each. Cancer stages were also recorded concerning treatment options. The differences in NG tube usage IC-surgery and IC-CRT groups were compared. The NG tube dependence rates were also presented. Results: The prognosis and tube dependence differed significantly between the two groups. The IC-surgery had a better prognosis compared to IC-CRT for oropharyngeal cancer. The findings indicated that NG tube dependence was greater in advanced tumor stage 4 compared to stages 1-3, and NG tube dependence rates were higher for patients who underwent chemoradiation therapy after induction chemotherapy. Swallowing function was better in the IC-surgery group compared to the IC-CRT group. Conclusions: Higher NG tube retention rates and NG dependence are found in OPSCC patients who choose CRT as their treatment and also in the advanced-stage group.

Background: 5-Aminolevulinic acid-guided surgery for adult gliomas has been approved by the European Medicines Agency and the US Food and Drug Administration, becoming a reliable tool for improving gross total resection rates and patient outcomes. This has led several medical centers to explore the off-label use of 5-ALA in the resection of pediatric brain tumors, assessing its efficacy and safety across various tumor types. However, given the differences between children and adults, the appropriateness of 5-ALA use in pediatric populations has not yet been fully established. Methods: We collected eligible publications from Embase, Scopus, PubMed, and Proquest, ultimately selecting 27 studies. Data extraction and retrospective analysis of 249 surgical cases were conducted to determine the current efficacy and safety of 5-ALA in pediatric brain tumors. The fluorescence rate and utility stratified by several clinical features, including WHO grade, tumor classification, and tumor location, were analyzed. Results: Most studies suggest that 5-ALA can enhance tumor identification in high-grade tumors, including glioblastomas and anaplastic astrocytomas. Changes in survival or recurrence rates associated with 5-ALA-guided resection have not been reported. None of the cases reported significant postoperative complications related to the use of 5-ALA. Conclusions: 5-ALA can aid in the resection of high-grade gliomas in pediatric patients. The efficacy of 5-ALA in low-grade gliomas and other tumors may require enhancement with additional tools or modified administration protocols. The safety of 5-ALA has reached a preliminary consensus, although further randomized controlled trials and data on survival and molecular characteristics are needed.

Background: Pharmacologically targeting the STING pathway offers a novel approach to cancer immunotherapy. However, small-molecule STING agonists face challenges such as poor tumor accumulation, rapid clearance, and short-lived effects within the tumor microenvironment, thus limiting their therapeutic potential. To address the challenges of poor specificity and inadequate targeting of STING in breast cancer treatment, herein, we report the design and development of a targeted liposomal delivery system modified with the tumor-targeting peptide iRGD (iRGD-STING-PFP@liposomes). With LIFU irradiation, the liposomal system exploits acoustic cavitation, where gas nuclei form and collapse within the hydrophobic region of the liposome lipid bilayer (transient pore formation), which leads to significantly enhanced drug release. Methods: Transmission electron microscopy (TEM) was used to investigate the physicochemical properties of the targeted liposomes. Encapsulation efficiency and in vitro release were assessed using the dialysis bag method, while the effects of iRGD on liposome targeting were evaluated through laser confocal microscopy. The CCK-8 assay was used to investigate the toxicity and cell growth effects of this system on 4T1 breast cancer cells and HUVEC vascular endothelial cells. A subcutaneous breast cancer tumor model was established to evaluate the tumor-killing effects and therapeutic mechanism of the newly developed liposomes. Results: The liposome carrier exhibited a regular morphology, with a particle size of 232.16 ± 19.82 nm, as indicated by dynamic light scattering (DLS), and demonstrated low toxicity to both HUVEC and 4T1 cells. With an encapsulation efficiency of 41.82 ± 5.67%, the carrier exhibited a slow release pattern in vitro after STING loading. Targeting results indicated that iRGD modification enhanced the system's ability to target 4T1 cells. The iRGD-STING-PFP@liposomes group demonstrated significant tumor growth inhibition in the subcutaneous breast cancer mouse model with effective activation of the immune system, resulting in the highest populations of matured dendritic cells (71.2 ± 5.4%), increased presentation of tumor-related antigens, promoted CD8+ T cell infiltration at the tumor site, and enhanced NK cell activity. Conclusions: The iRGD-STING-PFP@liposomes targeted drug delivery system effectively targets breast cancer cells, providing a new strategy for breast cancer immunotherapy. These findings indicate that iRGD-STING-PFP@liposomes could successfully deliver STING agonists to tumor tissue, trigger the innate immune response, and may serve as a potential platform for targeted immunotherapy.

Background: Metabolic syndrome increases the risk of developing various systemic cancers. The prevalence of metabolic syndrome in newly diagnosed glioblastoma patients is unknown. Further, there have been contradictory reports about how metabolic syndrome affects clinical outcomes. Therefore, the purpose of this study is to test the hypothesis that metabolic syndrome is associated with an increased prevalence of glioblastoma and worsened survival outcomes.

Methods: This retrospective cohort study examines seventy-three patients with isocitrate dehydrogenase (IDH)-wild-type glioblastoma as it provides a relatively homogeneous population to examine. Patient characteristics, vital signs, lab results, tumor molecular markers, and overall survival were analyzed. Patients with metabolic syndrome and individual risk factors were identified, and survival outcomes were examined.

Results: Our results demonstrate that there is a higher prevalence of metabolic syndrome in our cohort of patients with glioblastoma than in the general population (41% vs. 33%), though this effect is confounded by older age. We also demonstrate that after correction for confounding variables, metabolic syndrome is not significantly associated with overall survival (p = 0.1). When analyzing individual metabolic risk factors, we demonstrate that there is a significant association between the accumulation of metabolic risk factors and decreased survival (p = 0.03), and hyperglycemia emerges as a significant independent risk factor for decreased survival (p = 0.05).

Conclusions: These results suggest that metabolic risk factors can affect survival in patients with glioblastoma, which can have significant implications for clinical practice. These findings need to be further explored through further clinical and mechanistic studies.

Objectives: Additional adjuvant treatment in patients with rectal cancer with limited response to neoadjuvant treatment to mitigate their higher risk of treatment failure remains controversial. Methods: This is a post hoc analysis of a cohort study of 3 randomized phase 2 or 3 trials (CAO/ARO/AIO-94, -04, and -12 trial) that included 1948 patients with locally advanced rectal adenocarcinoma. After excluding patients with missing information, 1788 patients (1254 men and 524 women; median age: 62.6 years, age range: 19-84 years) were eligible. We analyzed the extent of tumor response and its association with the incidence of treatment failure after different neoadjuvant treatment approaches. Results: Tumor response was significantly enhanced with more intensive neoadjuvant treatment. After a median follow-up of 55 months for the entire cohort (IQR: 37 months-62 months), the incidence of treatment failure (TF) stratified by tumor response or post-neoadjuvant pathological outcome was not significantly affected by the intensity of neoadjuvant treatment, whereas the ypTNM stage was significantly associated with the risk of treatment failure. Conclusions: In this cohort study, we provide evidence that limited or no response to intensified neoadjuvant treatment protocols is not likely to be more strongly associated with an extensive risk of TF after 5-FU CRT+/- adjuvant chemotherapy.

Breast cancer (BCa) poses a severe threat to women's health worldwide as it is the most frequently diagnosed type of cancer and the primary cause of death for female patients. The biopsy procedure remains the gold standard for accurate and effective diagnosis of BCa. However, its adverse effects, such as invasiveness, bleeding, infection, and reporting time, keep this procedure as a last resort for diagnosis. A mammogram is considered the routine noninvasive imaging-based procedure for diagnosing BCa, mitigating the need for biopsies; however, it might be prone to subjectivity depending on the radiologist's experience. Therefore, we propose a novel, mammogram image-based BCa explainable AI (BCaXAI) model with a deep learning-based framework for precise, noninvasive, objective, and timely manner diagnosis of BCa. The proposed BCaXAI leverages the Inception-ResNet V2 architecture, where the integration of explainable AI components, such as Grad-CAM, provides radiologists with valuable visual insights into the model's decision-making process, fostering trust and confidence in the AI-based system. Based on using the DDSM and CBIS-DDSM mammogram datasets, BCaXAI achieved exceptional performance, surpassing traditional models such as ResNet50 and VGG16. The model demonstrated superior accuracy (98.53%), recall (98.53%), precision (98.40%), F1-score (98.43%), and AUROC (0.9933), highlighting its effectiveness in distinguishing between benign and malignant cases. These promising results could alleviate the diagnostic subjectivity that might arise as a result of the experience-variability between different radiologists, as well as minimize the need for repetitive biopsy procedures.

Background/objectives: The landscape of advanced melanoma treatments has shifted dramatically in recent years. Target therapy and immunotherapy have changed the management of patients with both metastatic (stage IV according to AJCC 8th ed.) and nodal (stage IIB/C and III) disease. As the use of novel agents has increased, so have the cutaneous toxicities associated with these medications. While most skin reactions are low-grade and can be managed conservatively with topical therapies, high-grade or life-threatening drug reactions can arise during therapy, requiring prompt dermatologic recognition and treatment. Given the survival benefit attributed to these new agents, treating skin toxicity and maintaining a patient's quality of life is of paramount importance.

Methods: We undertook a prospective, monocentric, and descriptive study in Bologna, Italy, including patients referred to the Oncologic Dermatology Unit of IRCCS AOU of Bologna who developed biopsy-proven cutaneous adverse events (AE) under treatment with immunotherapy for cutaneous melanoma with nodal (stage IIB/C, III) and metastatic (stage IV) disease from January 2016 to April 2024.

Results: In 202 identified patients, 75 (37.5%) developed skin AEs. Ipilimumab was causal for 48.1% of skin AEs, followed by nivolumab (37%) and pembrolizumab (31.4%). Recorded types of skin AEs included erythematous rash, vitiligo, alopecia, lichenoid, maculopapular, acneiform, urticarial, psoriasiform, granulomatous, eczematous, and severe cutaneous AEs, such as Erythema multiforme/Stevens-Johnson syndrome and bullous autoimmune dermatoses. Most AEs were low-grade [CTCAE 1-2] (97%) and typically occurred after 10 weeks of treatment.

Conclusions: This study comprehensively describes skin AEs occurring during systemic treatment with ICIs for cutaneous melanoma at a single center.

Background/Objectives: The presence of paraneoplastic syndromes (PNS) in patients with renal cell carcinoma (RCC) is associated with worse survival; however, little is known about whether resolution of PNS after intervention has any prognostic value. We sought to determine if resolution of PNS by one year after cytoreductive nephrectomy was significantly associated with improved overall survival (OS) and cancer-specific survival (CSS). Methods: We retrospectively reviewed a prospectively maintained nephrectomy database for patients with any histology metastatic RCC (mRCC) who underwent nephrectomy between 2000 and 2022. Patients with the necessary laboratory studies available within 90 days before and by one year after surgery were included for study. PNS resolution was defined as an abnormal value compared to established laboratory cutoffs by one year after surgery. Multiple PNS in one patient was allowed, and resolution of each PNS was measured separately. OS and CSS were assessed using Kaplan-Meier curves and Cox proportional hazards models. Results: A total of 253 patients met inclusion criteria. A total of 177 patients (70.0%) met criteria for at least one PNS resolution by one year. Five-year OS and CSS rates were 15.7% and 36.2% for no PNS resolved, 24.5% and 31.6% for 1 PNS resolved, and 43.0% and 58.2% for ≥2 PNS resolved, respectively (p < 0.001). On multivariable analysis, no PNS resolution was associated with worse OS (HR 2.75, p < 0.001) and CSS (HR 2.62, p < 0.001) compared to ≥2 PNS resolved. Conclusions: Resolution of preoperative PNS abnormalities by one year following surgery is associated with improved OS and CSS in patients with mRCC.

Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) has emerged as an effective and minimally invasive treatment for pancreatic lesions, particularly in patients at high surgical risk. Utilizing thermal energy, RFA induces the coagulative necrosis of the tissue and potentially triggers immunomodulation by releasing intracellular antigens. Numerous studies have confirmed the technical feasibility, safety, and efficacy of EUS-RFA in pancreatic neuroendocrine tumors and premalignant cystic lesions, with an acceptable profile of adverse events. The technique's potential immunomodulatory effects offer intriguing implications for the treatment of advanced pancreatic malignancies, encouraging further evaluation. This review paper aims to highlight the EUS-RFA principles, technology, and clinical applications in various pancreatic lesions and safety, and the future research directions.