Survival Time Of Patients Research Articles

SMARCA4-deficient undifferentiated tumor with high quality of life and far exceeding predicted survival: A case report.

SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently reported rare malignancy that can rapidly metastasize to tissues and organs throughout the body. The tumor is characterized by a lower response to platinum-based chemotherapy. More regrettably, the mean survival time of patients with this disease after diagnosis is only 4 to 7 months. A 58-year-old man was admitted to a hospital for fatigue, sudden syncope, and a mass-like shadow of his left upper lobe demonstrated by a pulmonary computed tomographic. Based on his subsequent clinical and pathological features, he was highly suspected of SMARCA4-UT. Combined with next-generation sequencing genetic testing and immunohistochemical examination results, the patient was diagnosed with SMARCA4-UT. The patient received a left upper lobectomy and lymph node dissection, four-course chemotherapy divided into 8 sessions with the use of paclitaxel simply, and a proper post-discharge self-care. The patient's operation and chemotherapy were all successful and he maintained a high quality of life after surgery that far exceeded his predicted survival. Early diagnosis, higher education level, attention to the disease and complications, reducing chemotherapy damage, adequate nutrient intake, relieving symptoms, controlling depression, and maintaining immunity and the ability to perform activities of daily living may all be the positive factors that can prolong the survival of patients with SMARCA4-UT.

Pre-stereotactic radiosurgery neutrophil-to-lymphocyte ratio predicts post-stereotactic radiosurgery survival of patients with brain metastases concurrently treated with immune checkpoint inhibitors.

Treatment with immune checkpoint inhibitors (ICIs) has shown clinical benefit for a wide range of cancer types. The neutrophil-to-lymphocyte ratio (NLR) reportedly correlates with survival time or progression-free survival in patients treated with ICIs. However, NLR has not yet been assessed in patients with brain metastases (BMs) receiving stereotactic radiosurgery (SRS) combined with concurrent ICIs. The authors investigated the predictive impact of NLR on the survival data of patients with BMs who received SRS with concurrent ICIs. The clinical records of patients who had undergone SRS with concurrent ICIs for BMs between January 2015 and August 2023 were retrospectively analyzed. NLR was calculated using the data obtained from the last examination prior to SRS. The optimal NLR cutoff value was identified by receiver operating characteristic (ROC) curve analysis for time-to-event data (overall survival [OS] ≤ 18 months). OS and intracranial disease progression-free survival (IC-PFS) rates were compared between the two NLR groups. Of the 185 eligible patients included, 132 were male. The median (IQR) patient age was 69 (61-75) years. The primary cancers were lung, genitourinary, skin, breast, gastrointestinal, and others in 132, 23, 22, 2, 2, and 4 patients, respectively. The post-SRS median OS and IC-PFS times for the entire cohort were 18.4 (95% CI 14.0-23.1) months and 9.2 (95% CI 6.9-10.8) months, respectively. ROC curve analysis identified the optimal NLR cutoff value for 18-month OS to be 5.0 (area under the curve 0.64, Youden index 0.31). Kaplan-Meier analysis revealed that patients with high NLR (> 5) had a significantly shorter OS (median survival time 10.9 months for 48 patients vs 22.2 months for 137 patients, HR 2.0, 95% CI 1.3-3.0, p < 0.001). Similarly, a significant difference in median IC-PFS was noted: 4.8 months with high NLR versus 10.7 months with low NLR (HR 1.7, 95% CI 1.2-2.5, p = 0.003). The authors found elevated pre-SRS NLR (> 5) to be associated with shorter OS and IC-PFS after SRS with concurrent ICIs for BMs. NLR is a simple, cost-effective, and widely accessible biomarker, which can thus be used for managing patients with BMs receiving SRS concurrently with ICIs. Further investigation in other large datasets is, however, required to validate these findings.

Expression of NAP1L5 in Patients with First Diagnosis of Acute Myeloid Leukemia and its Clinical Significance.

The objective of this study was to assess the expression levels of NAP1L5 in individuals diagnosed with acute myeloid leukemia (AML) and to investigate its clinical and prognostic significance in those with primary AML. Between June 2021 and June 2023, the Department of Hematology at the First Affiliated Hospital of Bengbu Medical University collected 100 bone marrow specimens from primary AML patients and 30 from individuals with idiopathic thrombocytopenic purpura (ITP) for this medical research study. The researchers gathered comprehensive clinical data from patients diagnosed with acute myeloid leukemia (AML). Quantitative real-time polymerase chain reaction (qRT-PCR) was utilized to measure the mRNA levels of NAP1L5 in both the ex-perimental and the control group. The investigation involved analyzing the association between NAP1L5 expres-sion related to AML, clinical features, and overall prognosis. The study employed the Kaplan-Meier method to evaluate the impact of NAP1L5 expression on the overall survival time (OS) in AML patients, while the Cox hazard regression model was used to identify significant prognostic factors. NAP1L5 was found to be significantly more expressed in individuals with AML compared to those with ITP. Patients diagnosed with AML and exhibiting elevated NAP1L5 expression levels correlated with older age, ineffective response to chemotherapy, and a more unfavorable prognosis compared to those with lower NAP1L5 expression. Additionally, the group with high expression demonstrated a noticeably decreased overall survival (OS), compared to the group with low expression. Furthermore, a significant association was observed between the elevated NAP1L5 expression levels and an unfavorable clinical outcome in patients diagnosed with AML. The initial exploration of the elevated expression of NAP1L5 in AML and its clinical significance offers potential targets for AML treatment and prognostic evaluation.

Nomogram for predicting the risk and prognosis of lung metastasis of four subtypes of breast cancer: A population-based study from SEER

BackgroundBreast cancer (BC) is the most diagnosed cancer worldwide, and patients' survival decreases with metastasis. We conducted a retrospective study using data derived from the Surveillance, Epidemiology, and End Results (SEER) database and clinicopathological data to construct a clinical predictive model to predict the risk and prognosis of lung metastasis (LM) in patients with different subtypes of BC and validate its performance. MethodsA total of 1650 patients from the SEER database between 2011 and 2015 were enrolled in this study. Cox regression analysis was performed to identify prognostic factors for breast cancer lung metastasis (BCLM). A nomogram was constructed using the independent prognostic factors. The concordance index (C-index), area under the curve (AUC) value, calibration curve, and decision curve analysis (DCA) were used to test the prediction accuracy of the nomogram. External validation (n = 112) was performed using clinical data from the Affiliated Hospital of Qinghai University and the General Hospital of Ningxia Medical University. ResultsMultivariate Cox regression analyses suggested that age, grade, surgery, chemotherapy, subtype, and liver, bone, and brain metastases were independent prognostic factors for overall survival (OS). Kaplan–Meier survival analysis showed that the median survival times of patients with human epidermal growth factor receptor 2 (HER2)-positive, luminal A, luminal B, and triple-negative BC were 25 (95% confidence interval [CI], 20–37), 27 (95% CI, 23–29), 35 (95% CI, 30–44), and 12 (95% CI, 11–14), respectively. The C-indexes of the nomogram for predicting OS of the SEER training, SEER validation, and clinical validation cohorts were 0.7, 0.6, and 0.6, respectively, and the calculated AUCs at 3 years were 0.765, 0.794, and 0.799, respectively. The calibration curve indicates that the nomogram possessed a high level of accuracy. ConclusionsOur nomogram demonstrates significant predictive value, indicating that molecular subtypes, brain metastasis, and liver metastasis are closely associated with the prognosis of patients with LM. This information can guide clinical practice.

Malignant Hip Flexion Failure Syndrome: An Oncologic Disease Compared to Malignant Psoas Syndrome.

Malignant psoas syndrome (MPS) causes painful hip immobilization when a malignant tumor reaches the psoas muscle. However, there exists a different condition in which a malignant tumor invades the psoas muscle, leading to hip flexion failure without painful hip immobilization. This study aimed to define malignant hip flexion failure syndrome (MHFFS) as tumors located in the upper lumbar region or at the lesser trochanter of the femur, near the origin or termination of the psoas muscle, and to compare its prevalence, characteristics, and outcomes with those of classical MPS. We analyzed 291 patients who received palliative radiotherapy (RT) in the lumbar, pelvic, and lower leg regions from 2013 to 2023. The prevalence of MPS and MHFFS, pathological features, distinctive clinical presentations, treatment modalities, and treatment outcomes have been summarized. We also defined the 'Clinical sign reported by Ishikawa and Teramura (IT sign)' to describe the characteristic action of lifting the affected lower leg with both hands in MHFFS cases and assessed its clinical significance. Among the 291 patients, 6 (2.1%) had MHFFS and 11 (3.8%) had MPS. MHFFS resulted from metastatic tumors in the 11th and 12th thoracic vertebrae, as well as the 1st and 2nd lumbar vertebrae or the lesser trochanter of the femur, and it was characterized by hip and groin pain along with hip flexion dysfunction. All cases showed a positive IT sign. The response to RT varied, with symptomatic improvement observed in 50% of the patients. MPS is characterized by tumor invasion of the psoas muscle, causing severe lumbosacral nerve pain. Strong opioids were used for pain management in all patients, and epidural anesthesia was required in some patients. The median survival time of patients with MPS and MHFFS was 13.2 months. MPS required opioids more potently than MHFFS, but MHFFS responded relatively well to early RT.

Efficacy and Safety of 125I Seed Implantation in the Treatment of Pelvic Recurrent Cervical Cancer Following Radiotherapy: A Single-Arm Meta-Analysis of Chinese Patients.

The study aimed to assess the efficacy and safety of 125I seed implantation in the treatment of pelvic recurrent cervical cancer following radiotherapy. This meta-analysis was registered in PROSPERO. We looked up relevant studies in the databases of CNKI, Wanfang, CBM, PubMed, Embase, Cochrane Library, and Web of Science. The endpoint measures include the objective response rate, disease control rate, progression-free survival, overall survival, and adverse events. The meta-analysis included six studies and a total of 246 patients. The pooled ORR of tumor response was 63%, and the DCR was 87%. The median PFS was 9.09 months, and the median OS was 13.46 months. The incidence of adverse events of Grade ≥III was 6%. In conclusion, this meta-analysis confirmed that 125I seed implantation has a good local control rate and high safety in the treatment of pelvic recurrent cervical cancer following radiotherapy, and can be used as a remedial treatment for pelvic recurrent cervical cancer following radiotherapy to prolong the survival time of patients. PROSPERO: CRD42023423857.

Segmentectomy and wedge resection are equivalent for the treatment of early-stage pulmonary carcinoid tumors: A retrospective cohort study

Currently, there is no consensus regarding the extent of surgery for stage I pulmonary carcinoid (PC) tumors, which encompass typical carcinoid (TC) and atypical carcinoid (AC) tumors. Sublobar resection includes segmental resection and wedge resection; the former is regarded as a type of anatomical resection that is better suited for tumor treatment. Therefore, it needs to be further verified whether differences exist in the effects of the two surgical methods on the survival time of patients. Propensity score matching (PSM) was used. The primary endpoints were cancer-specific survival (CSS) and overall survival (OS) time. Survival differences were analyzed via the Kaplan–Meier method and the log-rank test. There was no significant difference in survival between the sublobar resection and lobectomy groups after PSM in either the TC or AC tumor groups (all p > 0.05). A total of 1680 patients underwent pulmonary wedge resection (TC: n = 1547, AC: n = 133), and 398 patients underwent segmental resection (TC: n = 365, AC: n = 33). After PSM, there were no statistically significant differences in survival, regardless of whether OS or CSS was considered the primary endpoint (OS: p = 0.337; CSS: p = 0.470). Furthermore, segmental resection did not prolong patient survival time compared with wedge resection in different subgroup analyses on the basis of histology, age, and tumor size (all p > 0.05). Finally, the same results were obtained via multivariate Cox analysis (OS: p = 0.153; HR = 1.21; CSS: p = 0.351, HR = 1.32). Sublobar resection could be considered for patients with early-stage typical or atypical pulmonary carcinoid, provided that a rigorous lymph node evaluation is conducted. If the tumor is distant from the pulmonary hilum, either segmentectomy or wedge resection may be performed depending on the specific location of the tumor and the clinical condition of the patient.

SIRT1 silencing promotes EMT and Crizotinib resistance by regulating autophagy through AMPK/mTOR/S6K signaling pathway in EML4-ALK L1196M and EML4-ALK G1202R mutant non-small cell lung cancer cells.

Most EML4-ALK rearrangement non-small cell lung cancer (NSCLC) patients inevitably develop acquired drug resistance after treatment. The main mechanism of drug resistance is the acquired secondary mutation of ALK kinase domain. L1196M and G1202R are classical mutation sites. We urgently need to understand the underlying molecular mechanism of drug resistance to study the therapeutic targets of mutant drug-resistant NSCLC cells. The silent information regulator sirtuin1 (SIRT1) can regulate the normal energy metabolism of cells, but its role in cancer is still unclear. In our report, it was found that the SIRT1 in EML4-ALK G1202R and EML4-ALK L1196M mutant drug-resistant cells was downregulated compared with EML4-ALK NSCLC cells. The high expression of SIRT1 was related to the longer survival time of patients with lung cancer. Activation of SIRT1 induced autophagy and suppressed the invasion and migration of mutant cells. Further experiments indicated that the activation of SIRT1 inhibited the phosphorylation level of mTOR and S6K by upregulating the expression of AMPK, thus activating autophagy. SIRT1 can significantly enhanced the sensitivity of mutant cells to crizotinib, improved its ability to promote apoptosis of mutant cells, and inhibited cell proliferation. In conclusion, SIRT1 is a key regulator of drug resistant in EML4-ALK L1196M and G1202R mutant cells. SIRT1 may be a novel therapeutic target for EML4-ALK drug resistant NSCLC.

HDAC8 Enhances the Function of HIF-2α by Deacetylating ETS1 to Decrease the Sensitivity of TKIs in ccRCC.

Drug resistance after long-term use of Tyrosine kinase inhibitors (TKIs) has become an obstacle for prolonging the survival time of patients with clear cell renal cell carcinoma (ccRCC). Here, genome-wide CRISPR-based screening to reveal that HDAC8 is involved in decreasing the sensitivity of ccRCC cells to sunitinib is applied. Mechanically, HDAC8 deacetylated ETS1 at the K245 site to promote the interaction between ETS1 and HIF-2α and enhance the transcriptional activity of the ETS1/HIF-2α complex. However, the antitumor effect of inhibiting HDAC8 on sensitized TKI is not very satisfactory. Subsequently, inhibition of HDAC8 increased the expression of NEK1, and up-regulated NEK1 phosphorylated ETS1 at the T241 site to promote the interaction between ETS1 and HIF-2α by impeded acetylation at ETS1-K245 site is showed. Moreover, TKI treatment increased the expression of HDAC8 by inhibiting STAT3 phosphorylation in ccRCC cells is also found. These 2 findings highlight a potential mechanism of acquired resistance to TKIs and HDAC8 inhibitors in ccRCC. Finally, HDAC8-in-PROTACs to optimize the effects of HDAC8 inhibitors through degrading HDAC8 and overcoming the resistance of ccRCC to TKIs are synthesized. Collectively, the results revealed HDAC8 as a potential therapeutic candidate for resistance to ccRCC-targeted therapies.

Correlation between abdominal computed tomography signs and postoperative prognosis for patients with colorectal cancer.

Patients with different stages of colorectal cancer (CRC) exhibit different abdominal computed tomography (CT) signs. Therefore, the influence of CT signs on CRC prognosis must be determined. To observe abdominal CT signs in patients with CRC and analyze the correlation between the CT signs and postoperative prognosis. The clinical history and CT imaging results of 88 patients with CRC who underwent radical surgery at Xingtan Hospital Affiliated to Shunde Hospital of Southern Medical University were retrospectively analyzed. Univariate and multivariate Cox regression analyses were used to explore the independent risk factors for postoperative death in patients with CRC. The three-year survival rate was analyzed using the Kaplan-Meier curve, and the correlation between postoperative survival time and abdominal CT signs in patients with CRC was analyzed using Spearman correlation analysis. For patients with CRC, the three-year survival rate was 73.86%. The death group exhibited more severe characteristics than the survival group. A multivariate Cox regression model analysis showed that body mass index (BMI), degree of periintestinal infiltration, tumor size, and lymph node CT value were independent factors influencing postoperative death (P < 0.05 for all). Patients with characteristics typical to the death group had a low three-year survival rate (log-rank χ 2 = 66.487, 11.346, 12.500, and 27.672, respectively, P < 0.05 for all). The survival time of CRC patients was negatively correlated with BMI, degree of periintestinal infiltration, tumor size, lymph node CT value, mean tumor long-axis diameter, and mean tumor short-axis diameter (r = -0.559, 0.679, -0.430, -0.585, -0.425, and -0.385, respectively, P < 0.05 for all). BMI was positively correlated with the degree of periintestinal invasion, lymph node CT value, and mean tumor short-axis diameter (r = 0.303, 0.431, and 0.437, respectively, P < 0.05 for all). The degree of periintestinal infiltration, tumor size, and lymph node CT value are crucial for evaluating the prognosis of patients with CRC.

Prognostic significance of pyrimidine metabolism-related genes as risk biomarkers in hepatocellular carcinoma

Hepatocellular carcinoma (HCC), as a malignancy derived from liver tissue, is typically associated with poor prognosis. Increasing evidence suggests a connection between pyrimidine metabolism and HCC progression. The purpose of this study was to establish a model applied to the prediction of HCC patients’ overall survival. Transcriptomic data of HCC patients were downloaded from The Cancer Genome Atlas (TCGA) website. Pyrimidine metabolism-related genes (PMRGs) were collected from the Gene Set Enrichment Analysis (GSEA) website. Differential gene expression analysis was carried out on the HCC data, followed by an intersection of the differentially expressed genes (DEGs) and PMRGs. Subsequently, a prognostic model incorporating nine genes was established using univariate/multivariate Cox regression and Least absolute shrinkage and selection operator (LASSO) regression. Survival analysis demonstrated that the high-risk group defined by this model had considerably shorter overall survival than the low-risk group in both TCGA and Gene Expression Omnibus (GEO) datasets. Receiver operating characteristic (ROC) analysis indicated the good predictive capability of the model. CIBERSORT and single sample gene set enrichment analysis (ssGSEA) algorithms revealed significantly higher levels of Macrophages M0 and lower levels of natural killer (NK)_cells in the high-risk group compared to the low-risk group. The immunophenoscore (IPS) and the tumor immune dysfunction and exclusion (TIDE) score demonstrated that the model could significantly differentiate patients who would be more suitable for immunotherapy. Moreover, the CellMiner database was utilized to predict anti-tumor drugs significantly associated with the model genes. Collectively, the potential prognostic significance of pyrimidine metabolism in HCC was revealed in this study. The prognostic model aids in evaluating the survival time and immune status of HCC patients.

Treatment-free survival and partitioned survival analysis of patients with advanced renal cell carcinoma treated with nivolumab plus ipilimumab versus sunitinib: 5-year update of CheckMate 214

BackgroundImmunotherapy can be associated with prolonged disease control even after cessation of treatment without the need for further cancer-directed therapy. Treatment-related adverse events (TRAEs) can also persist after discontinuation of...

Neoadjuvant immunotherapy ushers in a new era of gastric cancer treatment

Recent advances in tumor immunology have made immunotherapy a new direction for neoadjuvant treatment of gastric cancer. Multiple clinical trials have confirmed that combining immunotherapy with chemotherapy and targeted therapy in the neoadjuvant treatment of gastric cancer can effectively improve treatment response and prolong patient survival time. This article aims to comment on the application of immunotherapy in the neoadjuvant treatment of gastric cancer, exploring its mechanisms, integration strategies with traditional treatments, safety, and personalized precision therapy in the hope of providing new insights and directions for the field of gastric cancer treatment.

Circulating levels of galectin-9 are a potential biomarker of survival in advanced non-small-cell lung cancer.

The immune system is recognized to have therapeutic potential to destroy cancer cells. Soluble T-cell immunoglobulin mucin domain-3 (sTIM-3) and its ligand galectin 9 (Gal-9) cause suppression of cytokine production, cell cycle arrest and cell death. sTIM-3 and Gal-9 levels may have prognostic implications in non-small-cell lung cancer (NSCLC) patients. This prospective cohort study was performed at Instituto de Medicina Integral Prof. Fernando Figueira, Recife, Pernambuco, Brazil. Fifty-eight patients were diagnosed with advanced NSCLC from January 2019 to January 2020. The age median was of 64.0 years. Soluble galectin-9 (sGal-9) levels in the smokers compared to nonsmoker patients (p < 0.0001). By using the receiver operating characteristic curve, we found that a baseline of 1694 pg/mL (cutoff). sGAL9 with specificity (72.2%), sensitivity (83.2%) and area under the curve = 0.8497 (p < 0.0004). Until 18.2 months, 46.8% and 72.9% were alive in the sGAL9low and sGAL9high groups, respectively (log-rank test; p = 0.02). The median survival was 15.9 months for sGAL9low (≤1694 pg/mL). This study indicated an association of tobacco with the release of circulating sGal-9 levels and the accuracy of sGal-9 as a potential biomarker predictive of survival time in advanced NSCLC patients. Furthermore, sGal-9 has may be a potential therapeutic target in the advanced NSCLC.

China clinical practice guideline for stage Ⅳ primary lung cancer (2024 edition)

Primary lung cancer (abbreviated as lung cancer) stands as the most prevalent malignant disease and the leading cause of cancer-related death in China, with an estimated 106.06×104 incident cases and 73.33×104 deaths in 2022. Due to the absence of effective early screening methods, most patients with lung cancer in China are in stage Ⅳ when diagnosed. Multi-disciplinary treatment based on systemic therapy is the treatment principle for patients with stage Ⅳ lung cancer. Chemotherapy remains the cornerstone, but its effectiveness is still unsatisfactory. In recent years, with the rapid development of molecular targeted therapy and immunotherapy, the treatment concept for stage Ⅳ lung cancer has been continually evolving, leading to significant improvements in patient treatment outcomes. To ensure timely updates on the global progress in the treatment of stage Ⅳ lung cancer and further improve the level of standardized diagnosis and treatment of stage Ⅳ lung cancer in China, Medical Oncology Branch of China International Exchange and Promotive Association for Medical and Health Care and Chinese Association for Clinical Oncologists organized experts to compile "China clinical practice guideline for stage Ⅳ primary lung cancer (2024 edition)". This guideline systematically and comprehensively updates epidemiological data, TNM staging, new drugs, treatment regimens, and new indications approved by China National Medical Products Administration before June 30, 2024, etc. Based on the " Clinical practice guideline for stage Ⅳ primary lung cancer in China(2021 version)" and the " Clinical practice guideline for stage Ⅳ lung cancer in China (2023 edition)." This guideline incorporates recommendation levels for therapeutic drugs and treatment flowcharts for stage Ⅳ lung cancer. The guideline covers common clinical issues and corresponding guidance in the diagnosis and treatment process of stage Ⅳ lung cancer. The guideline aims to guide the clinical practice of stage Ⅳ lung cancer, comprehensively improve the standardized diagnosis and treatment level in China, prolong the survival time of patients with stage Ⅳ lung cancer, and improve patients' quality of life.

TSP50 facilitates breast cancer stem cell-like properties maintenance and epithelial-mesenchymal transition via PI3K p110α mediated activation of AKT signaling pathway

BackgroundStudies have confirmed that epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC)-like properties are conducive to cancer metastasis. In recent years, testes-specific protease 50 (TSP50) has been identified as a prognostic factor and is involved in tumorigenesis regulation. However, the role and molecular mechanisms of TSP50 in EMT and CSC-like properties maintenance remain unclear.MethodsThe expression and prognostic value of TSP50 in breast cancer were excavated from public databases and explored using bioinformatics analysis. Then the expression of TSP50 and related genes was further validated by quantitative RT-PCR (qRT-PCR), Western blot, and immunohistochemistry (IHC). In order to investigate the function of TSP50 in breast cancer, loss- and gain-of-function experiments were conducted, both in vitro and in vivo. Furthermore, immunofluorescence (IF) and immunoprecipitation (IP) assays were performed to explore the potential molecular mechanisms of TSP50. Finally, the correlation between the expression of TSP50 and related genes in breast cancer tissue microarray and clinicopathological characteristics was analyzed by IHC.ResultsTSP50 was negatively correlated with the prognosis of patients with breast cancer. TSP50 promoted CSC-like traits and EMT in both breast cancer cells and mouse xenograft tumor tissues. Additionally, inhibition of PI3K/AKT partly reversed TSP50-induced activation of CSC-like properties, EMT and tumorigenesis. Mechanistically, TSP50 and PI3K p85α regulatory subunit could competitively interact with the PI3K p110α catalytic subunit to promote p110α enzymatic activity, thereby activating the PI3K/AKT signaling pathway for CSC-like phenotypes maintenance and EMT promotion. Moreover, IHC analysis of human breast cancer specimens revealed that TSP50 expression was positively correlated with p-AKT and ALDH1 protein levels. Notably, breast cancer clinicopathological characteristics, such as patient survival time, tumor size, Ki67, pathologic stage, N stage, estrogen receptor (ER) and progesterone receptor (PR) levels, correlated well with TSP50/p-AKT/ALDH1 expression status.ConclusionThe effects of TSP50 on EMT and CSC-like properties promotion were verified to be dependent on PI3K p110α. Together, our study revealed a novel mechanism by which TSP50 facilitates the progression of breast cancer, which can provide new insights into TSP50-based breast cancer treatment strategies.

CircCOL5A1 is involved in proliferation, invasion, and inhibition of ferroptosis of colorectal cancer cells via miR-1287-5p/SLC7A11.

Colorectal cancer (CRC) is the leading cause of cancer-related death globally. Circular RNA circCOL5A1 plays an oncogene function in a variety of tumors. However, the function of circCOL5A1 in CRC is still unknown. Here, we aimed to elucidate the function and mechanism of circCOL5A1 in CRC. The correlation between circCOL5A1 and CRC clinicopathological was assessed through chi-square. The relevance between circCOL5A1 and CRC patient survival time was evaluated by Kaplan-Meier analysis. The expressions of circCOL5A1 in CRC were determined via quantitative real-time PCR. The function of circCOL5A1 in CRC was analyzed with Cell Counting Kit-8, EdU assay, Transwell, detection of reactive oxygen species and Fe2+ levels, and Western blot analysis. Moreover, the mechanism of circCOL5A1 was determined by dual-luciferase reporter assay, RNA immunoprecipitation, and RNA pull-down. Finally, the role of circCOL5A1 in vivo was elucidated through a mouse xenograft model, hematoxylin-eosin staining, and immunohistochemistry. CircCOL5A1 expression was increased in CRC, and increased circCOL5A1 levels were related to TNM stage, lymph node metastasis, distant metastasis, and tumor differentiation in CRC patients, and CRC patients with high circCOL5A1 levels had a low overall survival rate. For the circCOL5A1 function in CRC, we found that circCOL5A1 knockdown weakened CRC cell proliferation and invasion, and enhanced cell ferroptosis. For the circCOL5A1 mechanism in CRC, we further confirmed that circCOL5A1 bound to miR-1287-5p, miR-1287-5p bound to SLC7A11. SLC7A11 was negatively interrelated to miR-1287-5p and was positively interrelated to circCOL5A1 in CRC tissues. Furthermore, interfering circCOL5A1 decreased SLC7A11 expression, and this trend was abolished through miR-1287-5p cotransfection. Rescue assays further demonstrated that circCOL5A1 knockdown alleviated CRC cell malignant phenotype via miR-1287-5p/SLC7A11. Moreover, interference with circCOL5A1 reduced CRC growth in vivo. CircCOL5A1 functioned as an oncogene in CRC via miR-1287-5p/SLC7A11.

Targeted Therapy of CEA-CAR-NK Cells Against Colorectal Cancer Cells

Objective: Investigate the cytotoxic effect of CAR-NK cells targeting CEA on colorectal cancer cells with positive CEA expression. Methods: The mRNA and protein levels of CEA in different CRC cell lines were detected by qRT-PCR and Western blot analysis. Lentiviral transduction was used to construct CAR-NK cells and empty vector CON-NK cells targeting CEA. Fluorescence microscopy and WB were used to determine whether the cells successfully constructed and expressed CAR structures. The effector NK cells were co-cultured with target cells, and the levels of LDH, IFN-γ, and GM-CSF were detected. The killing rate of effector cells was calculated, and the release of cytokines during the killing of target cells by different effector cells was compared. Results: The expression level of CEA in colorectal cancer patients was significantly higher than that in normal samples and other tumor samples, and the prognosis survival time of patients with high CEA expression was lower than that of CRC patients with low or no CEA expression (P &lt; 0.05). The CEA expression of the HT29 cell line was significantly higher than that of the SW1116 cell line at both the mRNA and protein levels. CEA-CAR-NK92 cells and CON-NK92 cells expressed green fluorescence under a microscope, and WB results showed that CEA-CAR-NK92 cells successfully expressed the CAR structure. Compared with CON-NK92 cells and NK92 cells, CEA-CAR-NK92 cells effectively killed HT29 cells (P &lt; 0.05). CEA-CAR-NK92 cells secreted a large amount of IFN-γ and GM-CSF during the killing of HT29 cells, while the cytokine secretion of CON-NK92 cells and NK92 cells was not significant (P &lt; 0.05). Conclusion: CAR-NK92 cells targeting CEA can effectively kill CEA-positive colorectal cancer cells.

ITIH1 suppresses carcinogenesis in renal cell carcinoma through regulation of the NF‑κB signaling pathway.

Renal cell carcinoma (RCC) is a common malignancy of the urinary system. Although traditional therapies, such as surgery assisted with chemotherapy have improved the quality of life and survival time of patients with RCC, patients with metastasis or recurrence benefit little from such therapies. At present, little is known about the underlying mechanisms of RCC, rendering treatment selection and implementation challenging. Therefore, investigating the cause and underlying mechanisms of RCC remain of importance to explore potential new avenues for its treatment. Inter-α-trypsin inhibitor heavy chain 1 (ITIH1) is an inflammation-associated gene reported to suppress the progression of liver cancer. However, its role in RCC remains poorly understood. Therefore, the present study aimed to investigate the role and mechanism of ITIH1 in RCC. Based on data obtained from The Cancer Genome Atlas database, ITIH1 expression was demonstrated to be significantly higher in tumor tissues compared with normal tissues, which was in turn negatively associated with the survival of patients with RCC. However, in RCC cells, ITIH1 was shown to be expressed at significantly lower levels compared with those in HK-2 cells. The discrepancy between tissues and cell lines might be due to the different environment of cell growth. ITIH1 knockdown in RCC cells significantly increased cell proliferation and invasion whilst significantly decreasing the apoptosis rate, compared with those in control cells (without ITIH1 knockdown). By contrast, overexpression of ITIH1 significantly inhibited cell proliferation and invasion in RCC cells. In terms of western blotting results, the phosphorylation levels of NF-κB were significantly increased following ITIH1 knockdown. The protein expression level of IκB significantly decreased whereas that of IKK, Cyclin D1, proliferating cell nuclear antigen and α-smooth muscle actin were significantly increased in ITIH1-knockdown cells, compared with those in the control cells (without ITIH1 knockdown). This suggests that the NF-κB pathway may be activated after ITIH1 knockdown. Following treatment with the NF-κB pathway inhibitor JSH-23 in combination with ITIH1 knockdown, RCC cell proliferation and invasion were significantly reduced compared with those after ITIH1 knockdown alone. In summary, results from the present study suggest that ITIH1 can serve an inhibitory role in the progression of RCC, which could potentially be inhibited through the NF-κB signaling pathway.

Survival disparities among racial groups with hepatic malignant tumors.

Investigating the impact of race on the clinicopathologic characteristics and prognosis of hepatic malignant tumors represents a complex and significant area of research. Notably, distinct differences exist among various racial groups in terms of the clinical manifestations, pathologic features, and prognosis of hepatic malignant tumors. To explore the effect of race on clinicopathologic features and prognosis of hepatic malignancies. Data from patients with hepatic malignancies diagnosed between 2000 and 2019 were collected from the Surveillance, Epidemiology, and End Results database and statistically analyzed. This study included 123558 patients with hepatic malignant tumors, among whom 21078 (17.06%) were Asian, 14810 (11.99%) were Black, and 87670 (70.95%) were white. The median survival times for patients with hepatic malignant tumors of different races were 12.56, 7.70, and 9.35 months for Asian patients, Black patients, and white patients, respectively. The 3-year survival rates for Asian, Black, and white patients were 29%, 19%, and 21%, respectively, and the 5-year survival rates were 22%, 13%, and 15%, respectively. The Kruskal-Wallis test indicated a significant difference in the survival time of patients with hepatic malignant tumors between different races (P < 0.001). Univariate analysis revealed gender disparities in the prognosis among different ethnic groups (Asian: P > 0.05; Black: P < 0.001; White: P < 0.05). Among Black patients, the prognosis was less affected by the degree of hepatic fibrosis than among Asian patients and white patients (Black patients: P < 0.05; Asian patients: P < 0.001; White patients: P < 0.001). Significant differences were observed in the median survival time among patients with hepatic neuroendocrine tumors and hepatoblastomas during pathologic staging between races. Tumor number was inversely related to the prognosis. Cox regression analyses revealed that T stage, M stage, surgery, chemotherapy, alpha-fetoprotein, and tumor size independently influenced prognosis. Age was a specific independent prognostic factor for white patients. Among the tumor stages, N stage is a self-reliant prognostic element specific to white patients. Conversely, radiotherapy and liver fibrosis were not self-reliant prognostic factors for Black patients. Income alone did not independently influence the prognosis of Asian patients. The prognosis of hepatic malignant tumors is better among Asian patients than among Black patients. The prognosis of hepatic malignant tumors among white patients is affected by multiple factors, including age and N stage.