Clinical & Translational Oncology最新文献

Reproductive cancers, such as ovarian, cervical, and endometrial carcinomas, have a poor prognosis in metastatic stages. Researchers are continuously seeking improved and safer methods to target cancer-related oncoproteins, addressing the limitations of current treatments, including their limited effectiveness, drug resistance, and off-target effects. Recent advancements in understanding the molecular mechanisms involved in the progress of reproductive cancers have provided valuable insights into potential targeted therapies. By engaging with oncoproteins and co-chaperones, heat-shock protein 90 (HSP90) regulates signaling networks and fixes protein folding errors in cancer cells. The potential of HSP90 inhibition as cancer-targeted treatments is underscored by the continuous discovery and testing of novel HSP90-targeted molecules for their antitumor properties in preclinical and clinical settings. Therefore, this study aims to shed light on the mechanism and recent research breakthroughs of HSP90, as well as provide an in-depth review of their therapeutic potential in reproductive cancers.

Introduction: The COVID-19 pandemic is a great burden worldwide, but its impact on patients with genitourinary cancer (GUC) is poorly characterized. This study aimed to characterize the clinical features and evolution of GUC patients affected by COVID-19 in Spain.

Patients and methods: SOGUG-COVID-19 was an observational ambispective non-interventional study that recruited patients with SARS-CoV-2 infection who had been treated for GUC in 32 Spanish hospitals. Data were collected from patients' medical records in a short period of time, coinciding with the first waves of COVID-19, when the mortality was also higher in the general population.

Results: From November 2020 to April 2021, 408 patients were enrolled in the study. The median age was 70 years, and 357 patients (87.5%) were male. Most frequent Cancer Origin was: prostate (40.7%), urothelial (31.4%) and kidney (22.1%). Most patients (71.3%) were diagnosed at the metastatic stage, and 33.3% had poorly differentiated histology. Anticancer treatment during the infection was reported in 58.3% of patients, and 21.3% had received immunotherapy prior to or concurrent with the infection. The most frequent COVID-19 symptoms were pyrexia (49.0%), cough (38.2%) and dyspnea (31.9%). Median age was higher for patients with pneumonia (p < 0.001), patchy infiltrates (p = 0.005), ICU admission (p < 0.001) and death (p < 0.001). Tumor stage was associated with complications (p = 0.006). The fatality rate was 19.9% and the 6-month COVID-19-specific survival rate was 79.7%.

Conclusion: Patients with genitourinary cancers seem exceptionally vulnerable to COVID-19 regardless of tumor type or anticancer therapy. Age and tumor stage were the only identified risk factors for severe COVID-19.

Aim: To examine melanoma mortality trends in Spanish Autonomous Communities from 1999 to 2022, focusing on gender and age differences.

Methods: Data from the National Statistics Institute were used to calculate age-standardized mortality rates (ASMRs). Joinpoint regression identified trend changes.

Results: Melanoma mortality varied significantly by region, gender, and age. Eastern Spain had higher male mortality, while western regions had lower rates. Asturias had higher female mortality, with lower rates in Andalusia, Extremadura, and Castilla-La Mancha. Men generally exhibited higher ASMRs than women, with variations across regions. While ASMRs remained stable in most areas, Madrid experienced a notable decline (AAPC: - 1.3%). A national trend reversal occurred in 2014 (AAPC: - 1.3%). For individuals aged 45-74 years, Catalonia saw a significant decrease (AAPC: - 1.1%, p < 0.05), whereas Andalusia experienced an increase (APC: 2.1% since 2007). Nationally, ASMRs for this age group declined (AAPC: - 0.7%). Among those aged 75 years and over, ASMRs varied considerably, with increases observed in Andalusia and Aragon. Nationally, male ASMRs rose (AAPC: 1.6% per year), while female rates were stable. Regional disparities were evident, with higher female mortality in the Balearic Islands and fluctuating rates in the Community of Madrid (an increase followed by a decrease after 2015). The gender gap in mortality varied across regions, with some areas showing a narrowing gap and others widening disparities.

Conclusion: Continuous monitoring of melanoma mortality, especially among men and older adults, is crucial. Public health efforts should address regional disparities, improve early detection, and enhance treatment access to optimize outcomes nationwide.

Purpose: Cervical cancer (CC) is a prevalent malignancy among women with high morbidity and poor prognosis. Sorting nexin 10 (SNX10) is a newly recognized cancer regulatory factor, while its action on CC progression remains elusive. Hence, this study studied the effect of SNX10 on CC development and investigated the mechanism.

Methods: The SNX10 level in CC and the overall survival of CC cases with different SNX10 expressions were determined by bioinformatics analysis in GEPIA. The SNX10 expression in tumor tissues and clinical significance were studied in 64 CC cases. The overall survival was assessed using Kaplan-Meier analysis. The formation of LC3 was evaluated using immunofluorescence. Cell invasion was measured using the Transwell assay. Epithelial-to-mesenchymal transition (EMT) was determined by observing cell morphology and assessing EMT marker levels. A xenograft tumor was constructed to evaluate tumor growth.

Results: SNX10 was elevated in CC tissues and cells, and the CC cases with high SNX10 levels exhibited poor overall survival. Besides, SNX10 correlated with the FIGO stage, lymph node invasion, and stromal invasion of CC. SNX10 silencing induced CC cell autophagy and suppressed CC cell invasion and EMT. Meanwhile, silenced SNX10 could suppress invasion and EMT via inducing autophagy. Furthermore, SNX10 inhibition suppressed the PI3K/AKT pathway. Moreover, silenced SNX10 restrained the tumor growth, autophagy, and EMT of CC in vivo.

Conclusion: SNX10 was enhanced in CC and correlated with poor prognosis. Silenced SNX10 induced autophagy to suppress invasion and EMT and inhibited the PI3K/AKT pathway in CC, making SNX10 a valuable molecule for CC therapy.

Background: Endometrial cancer (UCEC) is one of the most common malignant tumors in gynecology, and early diagnosis is crucial for its treatment. Currently, there is a lack of early screening tests specific to UCEC, and treatment advances are limited. It is crucial to identify more sensitive biomarkers for screening, diagnosis, and predicting UCEC. Previous studies have shown that UBE2T is involved in the development of various tumors such as breast cancer and liver cancer, but research on the role of UBE2T in UCEC is limited.

Methods: Using data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and UALCAN databases, we analyzed the differential expression of UBE2T mRNA and protein in endometrial cancer (UCEC), along with its clinical relevance. A total of 113 clinical samples were collected, and immunohistochemistry and Western blot analysis were employed to validate bioinformatics analysis results. Volcano plots were generated using UBE2T and its differentially expressed genes, and a protein-protein interaction (PPI) network was constructed. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), gene set enrichment analysis (GSEA), and immune infiltration analysis were used to predict the functional role of UBE2T in UCEC progression. Correlation between UBE2T expression and patient survival was analyzed using TCGA data, and Kaplan-Meier survival curves were plotted.

Results: UBE2T is significantly overexpressed in UCEC and correlates with poor prognosis. Its overexpression is closely associated with mitosis, cell cycle regulation, and histological grade in UCEC patients.

Conclusion: UBE2T is highly expressed in UCEC and suppresses anti-tumor immune responses in UCEC patients. It serves as a key participant in UCEC progression, associated with a range of adverse outcomes, and holds potential as a clinical diagnostic and prognostic biomarker.

Purpose: This study aimed to investigate the predictive value of intratumoral and peritumoral radiomics model for the cribriform component (CC) of invasive lung adenocarcinoma (LUAD).

Materials and methods: The 144 patients with invasive LUAD from our center were randomly divided into training set (n = 100) and internal validation set (n = 44) in a ratio of 7:3, and 75 patients from center 2 were regarded as the external validation set. Clinical risk factors were examined using univariate and multivariate logistic regression to construct the clinical model. We extracted radiomics features from gross tumor volume (GTV), gross and peritumoral volume (GPTV), and peritumoral volume (PTV), respectively. Radiomics models were constructed with selected features. A combined model based on the optimal Radscore and clinically independent predictors was constructed, and its predictive performance was assessed by receiver operating characteristic curve (ROC), calibration curve, and decision curve analysis (DCA).

Results: The area under curves (AUCs) of the GTV model were 0.882 (95% CI 0.817-0.948), 0.794 (95% CI 0.656-0.932), and 0.766 (95% CI 0.657-0.875) in the training, internal validation, and external validation sets, and the PTV model had AUCs of 0.812 (95% CI 0.725-0.899), 0.749 (95% CI 0.597-0.902), and 0.670 (95% CI 0.543-0.798) in the training, internal validation, and external validation sets, respectively. However, the GPTV radiomics model showed better predictive performance compared with the GTV and PTV radiomics models, with the AUCs of 0.950 (95% CI 0.911-0.989), 0.844 (95% CI 0.728-0.959), and 0.815 (95% CI 0.713-0.917) in the training, internal validation and external validation sets, respectively. In the clinical model, tumor shape, lobulation sign and maximal diameter were the independent predictors of CC in invasive LUAD. The combined model including independent clinical predictors and GPTV-Radscore show the considerable instructive to clinical practice, with the AUCs of 0.954(95% CI 0.918-0.990), 0.861(95% CI 0.752-0.970), and 0.794(95% CI 0.690-0.898) in training, internal validation, and external validation sets, respectively. DCA showed that the combined model had good clinical value and correction effect.

Conclusion: Radiomics model is a very powerful tool for predicting CC growth pattern in invasive LUAD and can help clinicians make the strategies of treatment and surveillance in patients with invasive LUAD.

Purpose: While treatments for primary brain tumors increase survival, they have cognitive sequelae. Neurocognition's anatomical distribution makes it susceptible to brain damage. This study aims to evaluate the contribution of radiotherapy on short-term cognitive impairment.

Methods/patients: Using a prospective database of cognitive rehabilitation in adults operated on for primary brain tumors, a retrospective sub-analysis of the contribution of radiotherapy was performed. Thirty-four subdivisions of 12 neurocognitive regions were delineated in 48 irradiated patients and 30 non-irradiated patients. In the first group, the correlation between radiation dose and deterioration was evaluated. In all patients, the impact of tumor and surgical changes on dysfunction was calculated and compared with dose-dependent response.

Results: The correlation between cognitive status and radiation dose is especially strong and significant in the left hemisphere and in specific subdivisions such as the posterior hippocampus or the dorsolateral prefrontal cortex, with the left prevailing over posterior dominance. Memory is the most affected domain 1 month after radiotherapy, as attention is three months later. The hippocampus is involved in various cognitive domains in addition to memory. The prefrontal subregions and the genu of the corpus callosum are more affected by the relationship with disease and surgical changes than by radiation exposure. Patients ongoing a course of radiotherapy do not benefit from concurrent cognitive rehabilitation.

Conclusions: There is a correlation between the dose of radiation received by several encephalic regions and degree of short-term domain-specific cognition decline, considering other factors of risk and cognitive rehabilitation.

Purpose: This scoping review aims to deepen the understanding of end-of-life anticancer drug use in lung cancer patients, a disease marked by high mortality and symptom burden. Insight into unique end-of-life treatment patterns is crucial for improving the appropriateness of cancer care for these patients.

Methods: Comprehensive searches were carried out in Medline and Embase to find articles on the utilization of anticancer drugs in the end of life of lung cancer patients.

Results: We identified 68 publications, highlighting the methodological characteristics of studies including the timing of the research, disease condition, treatment regimen, type of treatment, and features of the treatment. We outlined the frequency of anticancer drug use throughout different end-of-life periods.

Conclusion: This review provides a comprehensive overview of primary studies exploring end-of-life treatments in lung cancer patients. Methodological inconsistencies pose many challenges, revealing a notable proportion of patients experiencing potential overtreatment, warranting more standardized research methods for robust evaluations.