Cancer Management and Research最新文献

Purpose: Cervical cancer is the fourth leading cause of cancer-related death in women. Furthermore, owing to its significant risk of recurrence or metastasis, the overall prognosis of patients with cervical cancer remains poor. Activating transcription factor 5 (ATF5) plays a crucial role in cell proliferation, survival, and apoptosis, and has been implicated in the progression of various types of cancer. However, the biological function and precise mechanism of ATF5 in cervical cancer remain unclear. This study, aimed to explore the function of ATF5 and its potential mechanisms in cervical cancer.

Patients and methods: Quantitative real-time PCR, Western blot and immunohistochemistry were used to detect the expression of ATF5 in cervical cancer tissues and cell lines. Knockdown ATF5 expression in cervical cancer cell lines was constructed using lentivirus-mediated shRNA to explore the role of ATF5 in cervical cancer through cell viability, transwell, and wound healing experiments. The expression of Wnt3a and β-catenin were investigated using quantitative real-time PCR and Western blot.

Results: ATF5 was overexpressed in cervical cancer, and upregulation of ATF5 expression was associated with a poor prognosis. ATF5 knockdown inhibited the proliferation, migration and invasion abilities of cervical cancer cells. Furthermore, the downregulation of ATF5 led to the suppression of Wnt3a and β-catenin expression, which are key molecules in the Wnt/β-catenin signaling pathway.

Conclusion: ATF5 promotes tumorigenic capability in cervical cancer through the Wnt/β-catenin signaling pathway. ATF5 may be a potential prognostic biomarker and therapeutic target in the management of cervical cancer.

Locally advanced rectal cancer (LARC) is a common malignancy that is often managed with neoadjuvant radiotherapy to downstage the tumor and increase the rate of complete response. Recent evidence suggests that total neoadjuvant therapy (TNT) may further improve complete response rates and overall survival compared to conventional treatment methods. This case report describes a 61-year-old male patient with LARC who achieved a clinical complete response following TNT. The treatment regimen followed the CinClare study protocol, which included radiotherapy targeting both the rectum and regional lymph nodes, in combination with chemotherapy consisting of irinotecan and capecitabine. After concurrent chemoradiotherapy, the patient underwent six additional cycles of consolidation chemotherapy, leading to a near-complete clinical response. This case demonstrates the potential effectiveness of a high-intensity, dose-dense regimen involving synchronous radiotherapy followed by a six-cycle consolidation chemotherapy course aimed at optimizing organ preservation. This approach highlights a novel model for enhancing organ preservation in patients with low-grade LARC.

Objective: This study aims to assess the clinical significance of the peripheral blood neutrophil-to-lymphocyte ratio (NLR) in predicting chemotherapy outcomes for patients with small cell lung cancer (SCLC).

Methods: A cohort of 44 patients diagnosed with SCLC between January 2021 to June 2022 at Fuyang People's Hospital was selected for analysis. All patients in this group received a first-line platinum-based doublet chemotherapy regimen. In parallel, a control group consisting of 44 healthy individuals undergoing routine physical examinations at the same hospital was also selected. Fasting venous blood samples were collected in the morning within one week before the initiation of chemotherapy, and a complete blood cell count was performed to calculate the NLR.

Results: The NLR in the plasma of patients with SCLC was significantly elevated compared to that of healthy individuals (P < 0.01). After two cycles of chemotherapy, there were no statistically significant differences in plasma NLR in SCLC patients compared to pre-chemotherapy levels (P > 0.05). However, in the subgroup of patients with a partial response (PR) to treatment, the NLR decreased to 2.625 (95% CI: 1.900, 3.625), down from a pre-chemotherapy level of 3.430 (2.688, 4.800) (Z = -3.127, P = 0.002). Conversely, in patients whose disease progressed (PD) following chemotherapy, the NLR increased to 3.880 (95% CI: 2.953, 5.223) from a pre-chemotherapy level of 2.060 (1.915, 2.968) (Z = -2.521, P = 0.012).

Conclusion: The dynamic variations in the peripheral blood NLR before and after chemotherapy in patients with SCLC are strongly associated with the efficacy of first-line chemotherapy regimens. These changes in NLR levels may serve as a crucial indicator for predicting the effectiveness of first-line chemotherapy in patients with SCLC.

Purpose: In Norway, 5-year survival rates of patients with renal cell carcinoma (RCC) are increasing. The objective of this study was to describe the survival of real-world patients with metastatic RCC (mRCC) across Norway and to identify associated factors. The results may provide additional information on the benefits of tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) in clinical practice.

Patients and methods: We performed a longitudinal, retrospective, non-interventional cohort study using data from four national registries. The study included adults diagnosed with mRCC between 1 January 1995 and 31 December 2018. Primary endpoint was to evaluate overall survival (OS) in all included patients. Secondary endpoints included further analysis of treatment patterns and possible impact on OS. Secondary endpoint analysis was performed in patients diagnosed with mRCC between 1 January 2008 and 31 December 2018, as complete data on systemic therapies were available from 2008 and onwards.

Results: In total, 4078 patients were diagnosed with mRCC in the period from 1995 to 2018. The median OS since initial mRCC diagnosis was 1.17 years. OS appeared to improve over time, 5-year OS was 10% in patients diagnosed in the period 1995-2001 compared to 25% in 2012-2015. The secondary analysis included 2338 patients. Fifty-five percent (55%) of the patients received systemic treatment. No differences were observed in the number of treatment lines administered over time or in the number of lines of treatment administered according to tumor histology. Among 343 patients who received ≥3 treatment lines, we observed longer OS in patients who received an ICI as a part of their treatment, with a median OS of 4.51 compared to 2.31 years.

Conclusion: Provision of information into registries is mandatory in Norway. This retrospective, registry-based study provides real-world evidence on patient outcomes and treatments of the Norwegian patients with mRCC in the period from 1995 to 2018.

Background: Signaling pathways centered on the G-protein ADP-ribosylation factor 6 (Arf6) and its downstream effector ArfGAP with the SH3 Domain, Ankyrin Repeat and PH Domain 1 (AMAP1) drive cancer invasion, metastasis, and therapy resistance. The Arf6-AMAP1 pathway has been reported to promote receptor recycling leading to programmed cell death-ligand 1 (PD-L1) overexpression in pancreatic ductal carcinoma. Moreover, AMAP1 regulates of nuclear factor-kappa B (NF-κB), which is an important molecule in inflammation and immune activation, including tumor immune interaction through PD-L1 regulation. In this study, we investigated the function of AMAP1 on PD-L1 expression using lung cancer cells.

Methods: We used two non-small cell lung cancer cell lines. Protein expression was evaluated by Western blotting. AMAP1 and NF-kB expression were reduced by conventional siRNA methods, and osimertinib was used as an epithelial growth factor receptor (EGFR) inhibitor. Multiple analysis of receptor tyrosine kinases (RTKs) was conducted using a semi-comprehensive RTKs assay.

Results: We found that AMAP1 inversely regulated PD-L1 expression. Based on these results, we examined the activation levels of RTKs associated with both AMAP1 and PD-L1. Following a semi-comprehensive phosphorylated RTK assay, we observed the upregulation of phosphorylated EGFR (pEGFR) led by the downregulation of AMAP1. The inhibition of pEGFR by osimertinib downregulates PD-L1 expression. We investigated the relationships between AMAP1, NF-κB, and PD-L1 expression. AMAP1 knockdown upregulated the expression of both NF-κB and PD-L1. Subsequently, NF-κB knockdown downregulated PD-L1 levels, while double knockdown of AMAP1 and NF-κB, restored PD-L1 expression.

Conclusion: AMAP1 may inversely regulate PD-L1 through negative feedback of pEGFR and activation of NF-κB in NSCLC cell lines.

Purpose: To investigate the impact of Intensity-Modulated Radiation Therapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) on hippocampal radiation dosage and psychological status in patients newly diagnosed with nasopharyngeal carcinoma (NPC).

Patients and methods: A retrospective analysis was conducted on 269 NPC patients who received initial treatment between January 2013 and April 2022. Patients were categorized into the IMRT group and the VMAT group based on the radiotherapy technique employed. The differences in hippocampal doses for NPC patients at different stages between the two groups were analyzed. The Hospital Anxiety and Depression Scale (HADS) was used to assess patients' anxiety and depression states. Before radiotherapy, patients with anxiety scores (HADS-A) between 0 and 10 points were included to analyze the differences in anxiety occurrence rates between IMRT and VMAT techniques. Similarly, patients with depression scores (HADS-D) between 0 and 10 points were included to analyze the differences in depression occurrence rates between the two radiotherapy techniques.

Results: In patients with T1-2 stage, those treated with IMRT had significantly higher hippocampal doses compared to those treated with VMAT. Furthermore, after radiotherapy, the occurrence rates of anxiety (HADS-A ≥ 11) and depression (HADS-D ≥ 11) in the IMRT group were 27.3% and 19.5%, respectively, while in the VMAT group, they were 9.5% and 7.4%, both showing significant statistical differences (P=0.010, P=0.035). However, there was no significant correlation between the radiotherapy technique and anxiety or depression occurrence rates in patients with T3-4 stage. Additionally, age and gender exhibited certain influences on psychological status.

Conclusion: In the absence of hippocampal protection, opting for a VMAT treatment plan over IMRT may potentially reduce the incidence of anxiety and depression. This perspective offers new insights for optimizing treatment strategies and improving quality of life.

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related deaths worldwide. Mutations within the TP53 gene represent critical molecular events in NSCLC, contributing to the tumorigenesis in the pulmonary epithelial tissues. TP53 is a widely researched prognostic indicator in NSCLC, and pathological investigations have revealed a weak to mild negative predictive effect for TP53. Mutated p53 protein may have some pro-oncogenic impact, and the variations may change tumor inhibitors into oncogenes. The diverse mutational spectrum of TP53 in NSCLC with different mutations is linked to varied treatment responses. In contrast, first-line chemotherapeutics to this progress are limited, however, randomized trials with new chemotherapeutics have shown significant survival benefits. This review highlighted the critical influence of TP53 gene mutations on pathological-sensitivity and overall survival outcomes in NSCLC. Further research is needed to explore TP53 mutation-specific pathways and their effects on NSCLC progression and treatment effectiveness.

Introduction: Superior orbital fissure syndrome (SOFS) is a rare condition that involves damage to multiple structures within the superior orbital fissure, often caused by trauma, inflammation, or tumors. Lung adenocarcinoma, known for its propensity to metastasize, can lead to orbital metastases, which can manifest as SOFS. This case underscores the diagnostic and therapeutic challenges associated with such rare metastatic presentations.

Case presentation: A 60-year-old woman with a history of left lung adenocarcinoma presented with left eyelid ptosis and fixed eye position following hair dyeing. Despite initial treatments and imaging, her condition persisted. Subsequent imaging and thorough clinical evaluation revealed metastasis to the left superior orbital fissure. The patient was treated with volumetric modulated arc therapy (VMAT), leading to significant clinical improvement and reduction of the orbital mass.

Conclusion: This case highlights the critical role of comprehensive diagnostic evaluation and communication between specialists in managing rare metastatic conditions. It also demonstrates the efficacy of localized radiotherapy in treating such uncommon presentations of lung cancer metastasis.

Background: Cancer immunotherapy is an advanced therapeutic approach that harnesses the body's immune system to target and eliminate tumor cells. Traditional Chinese medicine (TCM), with a history rooted in centuries of clinical practice, plays a crucial role in enhancing immune responses, alleviating cancer-related symptoms, and reducing the risks of infections and complications in cancer patients.

Methodology: This review systematically examines the current literature on TCM-based formulations in cancer immunotherapy. It explores the mechanisms by which TCM augments immune responses, particularly focusing on how these formulations influence both innate and adaptive immunity. Various TCM herbs and compounds, their active ingredients, and their application in cancer prevention and treatment were analyzed through an integrated review of preclinical studies, clinical trials, and molecular mechanistic investigations.

Results: TCM formulations contribute to cancer therapy by modulating the body's internal environment to improve immune defense. They enhance the immune system's ability to detect and destroy cancer cells, promote apoptosis in tumor cells, inhibit tumor growth and metastasis, and augment the effectiveness of conventional cancer treatments. The review highlights specific TCM herbs and formulations that have demonstrated significant anti-cancer properties, including their ability to strengthen immune responses and provide synergistic effects with existing cancer therapies.

Conclusion: TCM-derived formulations represent a promising addition to cancer immunotherapy. The mechanisms through which these formulations enhance anti-tumor immunity are multifaceted, involving modulation of immune cell activity, apoptosis induction, and suppression of tumor progression. As cancer immunotherapy evolves, the integration of TCM into conventional treatment regimens may offer enhanced therapeutic efficacy, reduced side effects, and improved overall outcomes for cancer patients. Further clinical research is needed to fully elucidate the therapeutic potential and safety of TCM-based immunotherapeutic strategies in cancer care.

Objective: Our research has pinpointed the gut microbiome's role in the progression of various pathological types of non-small cell lung cancer (NSCLC). Nonetheless, the characteristics of the gut microbiome and its metabolites across different clinical stages of NSCLC are yet to be fully understood. The current study seeks to explore the distinctive gut flora and metabolite profiles of NSCLC patients across varying TNM stages.

Methods: The research team gathered stool samples from 52 patients diagnosed with non-small cell lung cancer (NSCLC) and 29 healthy individuals. Subsequently, they performed 16S rRNA gene amplification sequencing and untargeted gas/liquid chromatography-mass spectrometry metabolomics analysis.

Results: The study revealed that the alpha-diversity of the gut microbiome in NSCLC patients at different stages did not exhibit statistically significant differences. Notably, Lachnospira and Blautia were more abundant in healthy controls. The distribution of gut microbial species in patients with varying stages of NSCLC was uneven, with Bacteroides and Bacteroidaceae being most prevalent in stage T2, and Prevotella dominating in stage T4. Levels of Ruminococcus gnavus were notably elevated in stages N3 and M. The genus levels of Klebsiella, Parabacteroides, and Tannerellaceae were higher in stage II patients. Rodentibacter was the bacterium with increased levels in stage III NSCLC patients. Further metabolomics studies revealed significantly elevated levels of quinic acid and 3-hydroxybenzoic acid in the healthy control group. In contrast, Stage I+II non-small cell lung cancer (NSCLC) patients exhibited reduced levels of L-cystathionine. Notably, quinic acid, phthalic acid, and L-lactic acid were observed to be increased in Stage III+IV NSCLC patients.

Conclusion: Compared to the analysis of a single microbial dataset, this study provides deeper functional insights by incorporating comprehensive metabolomic profiling. This approach demonstrates that both the gut microbiome and associated metabolites are altered in NSCLC patients across different clinical stages. Our findings may offer novel perspectives on the pathogenesis of NSCLC at various TNM stages. Further research is warranted to validate and clinically apply these potential biomarkers.