American journal of cancer research最新文献

{"title":"Construction and clinical validation of risk model for predicting bone cement leakage after the surgical management of spinal metastases.","authors":"Yanrong Liu, Ziyan Zhang, Jianzhong Huo","doi":"10.62347/JAIR5009","DOIUrl":"10.62347/JAIR5009","url":null,"abstract":"<p><p>This study aimed to comprehensively analyze the risk factors associated with bone cement leakage (LCK) during the surgical management of spinal metastases, construct a joint risk model for predictive assessment, and validate the clinical applicability of the risk model in an independent patient cohort. A retrospective analysis was conducted on patients who underwent surgery for spinal metastases between February 2022 and June 2023. Patients were divided into a non-LCK group (n=134) and an LCK group (n=86) based on the presence or absence of bone cement leakage after surgery. Additionally, a validation group was established, consisting of 21 patients with LCK and 65 patients without. Analysis focused on patient demographics, intraoperative parameters, LCK location, complications, pain management, and improvements in activities of daily living (ADL). Logistic regression, calibration curve, clinical impact curve (CIC) analysis, decision curve analysis (DCA) and receiver operating characteristic (ROC) analysis were used to assess the risk factors and construct a joint risk model. There were significant differences between the two groups in pathologic fracture, Tomita classification, posterior wall destruction, injected laterality, injected bone cement volume, radicular pain, pulmonary embolism, and medullary compression. Pathologic fracture, radicular pain, pulmonary embolism, and medullary compression were positively correlated with the occurrence of LCK, while Tomita classification, posterior wall destruction, injection laterality, and injected bone cement volume were negatively correlated with the occurrence of LCK. Pathological fracture, Tomita classification, posterior wall destruction, injected laterality, injected bone cement volume, and specific postoperative complications were identified as significant risk factors associated with LCK. The constructed joint risk model, incorporating these risk factors, demonstrated substantial predictive value, with an Area Under the Curve (AUC) of 0.885. Clinical validation in an independent patient cohort further confirmed the predictive power of the joint risk model, with an AUC of 0.846. This study underscores the multifactorial nature of LCK in surgical management of spinal metastases, providing valuable insights for risk assessment and management.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 10","pages":"4841-4854"},"PeriodicalIF":3.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560829/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Survival benefit of surgery in elderly patients with locally advanced rectal cancer.","authors":"Hsuan-Yi Huang, Chia-Jen Tsai, Chia-Lin Chou, Li-Chin Cheng, Yu-Hsuan Kuo, Yu-Cih Wu, Chung-Han Ho, Ching-Chieh Yang","doi":"10.62347/XSKR3897","DOIUrl":"10.62347/XSKR3897","url":null,"abstract":"<p><p>Neoadjuvant therapy followed by radical surgery is standard for locally advanced rectal cancer (LARC). However, compared to younger patients, elderly patients often had multiple commodities and may refuse surgery due to being medically unfit or the high risk of operative mortality. This study aims to explore the effects of surgery on short- and long-term mortality in elderly LARC patients using a nationwide cancer registry. The cohort included 6211 patients aged over 65, with 2556 matched through propensity scoring for comparison between surgery (N = 1704) and non-surgery (N = 852) groups. The Cox proportional hazard model compared mortality between these groups. Our results showed that the elderly LARC patients who underwent surgery were more likely to be younger (65-75 years), have clinically-positive lymph nodes, and no comorbidities. Surgery was associated with significantly lower 3-month, 6-month, and 5-year mortality rates, with a greater absolute survival benefit (adjusted hazard ratio [aHR], 4.78; 95% CI, 2.71-8.43; aHR, 4.50; 95% CI, 3.07-6.58 and aHR, 3.81; 95% CI, 3.21-4.51). In stratified analysis, surgery remains provide significantly survival benefit according different age, gender and clinical classification. Furthermore, among non-surgical patients, those receiving chemoradiation had better survival outcomes compared to those receiving radiation, chemotherapy, or no treatment (all P < 0.001). This study highlights the survival advantage of surgery in elderly LARC patients and offers valuable guidance for clinical decision-making.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 10","pages":"4956-4968"},"PeriodicalIF":3.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560825/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646604","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predict value of tumor markers combined with interleukins for therapeutic efficacy and prognosis in ovarian cancer patients.","authors":"Fang Cheng, Xijia Ma, Zhenyang Cheng, Yami Wang, Xuelin Zhang, Chunzheng Ma","doi":"10.62347/GSRD2580","DOIUrl":"10.62347/GSRD2580","url":null,"abstract":"<p><p>Ovarian cancer (OC) is the most prevalent and fatal malignancy of the female reproductive system, with the majority of patients diagnosed at an advanced stage due to the lack of early screening. Despite surgery and chemotherapy being the standard treatments, overall survival rates have not improved significantly, highlighting the need for new biomarkers for therapeutic efficacy and prognostic evaluation. This study aimed to clarify the application value of tumor markers (TMs), including carbohydrate antigen 125 (CA125), alpha-fetoprotein (AFP), and carcinoembryonic antigen (CEA), combined with interleukins (ILs), such as IL-1β, IL-2, IL-6, IL-8, and IL-10, in the evaluation of therapeutic efficacy and prognosis of OC, and to establish a prediction model. A retrospective analysis was conducted on 184 OC patients treated at the Affiliated Hospital of Henan University of Traditional Chinese Medicine from February 2020 to February 2023. Serum levels of CA125, AFP, and CEA were quantified by chemiluminescence immunoassay, and ILs by enzyme-linked immunosorbent assays. Significant decreases in CA125, AFP, CEA, IL-1β, IL-2, IL-6, and IL-10 levels were observed after treatment (all P<0.001), while IL-8 levels showed no significant change (P=0.597). The death group exhibited notably higher levels of CA125, IL-6, and IL-8 than the survival group (all P<0.001). Cox regression analysis identified CA125, IL-8, histological grading, ascites, intravascular tumor thrombus, and International Federation of Gynecology and Obstetrics (FIGO) staging as independent prognostic factors. The Nomogram model based on these factors showed strong predictive ability in predicting patient mortality with an area under the curve (AUC) of 0.756. In conclusion, the combination of TMs and ILs is valuable in evaluating therapeutic efficacy and prognosis in OC. Dynamic monitoring of CA125, IL-6, and IL-8 can guide clinical treatment adjustments, improving diagnostic accuracy and prognosis reliability.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 10","pages":"4868-4879"},"PeriodicalIF":3.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560821/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646561","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk factor analysis and development of predictive models for osteoradionecrosis in patients with nasopharyngeal carcinoma after concurrent chemoradiotherapy.","authors":"Ming-Jie Gong, Zhi-Gang Lai, Yun-Xia Zhang, Na Hu","doi":"10.62347/RIWX7204","DOIUrl":"10.62347/RIWX7204","url":null,"abstract":"<p><p>Nasopharyngeal carcinoma (NPC) is a malignant tumor that targets the nasopharyngeal mucosal epithelium. Concurrent chemoradiotherapy (CCRT) is a pivotal treatment modality for NPC, yet it poses a risk for osteoradionecrosis (ORN), a complication that can impede further treatment. This study sought to explore the risk factors for ORN in NPC patients post-CCRT and to construct predictive models. We performed a retrospective analysis of clinical data from 417 NPC patients treated with CCRT at the Affiliated Hospital of Jiangnan University, with 204 patients from Longyan First Hospital as a validation cohort for the models. Our findings indicated that a high radiation dose, tooth extraction after radiotherapy, inadequate oral hygiene, smoking, anemia, and advanced T staging were associated with an elevated risk of ORN in NPC patients following CCRT. We formulated risk prediction models for ORN utilizing a nomogram, gradient boosting machine (GBM), and random forest (RF) algorithms. The area under the curve (AUC) was 0.813 (95% CI: 0.724-0.902) for the nomogram model in the validation cohort, 0.821 (95% CI: 0.732-0.910) for the GBM, and 0.735 (95% CI: 0.614-0.855) for the RF. Delong's test indicated no statistically significant differences in the AUC values among the three models. The nomogram has strong performance across both the training and validation cohorts, featuring a straightforward structure that is both intuitive and comprehensible. Taking into account the model's discriminative power, generalizability, and clinical practicability, the nomogram was proven to be highly applicable in the current study.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 10","pages":"4760-4771"},"PeriodicalIF":3.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560816/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142650560","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NRG1 secreted by cancer-associated fibroblasts contributes to enzalutamide resistance in prostate cancer cells.","authors":"Chunyu Wang, Hongwen Cao, Peng Sun, Lei Chen, Yigeng Feng, Renjie Gao","doi":"10.62347/OTTR3398","DOIUrl":"10.62347/OTTR3398","url":null,"abstract":"<p><p>While androgen deprivation therapy (ADT) continues to be a fundamental aspect of prostate cancer treatment, the development of castration-resistant prostate cancer (CRPC) emphasizes the necessity for a more profound understanding of the tumor microenvironment (TME). Normal fibroblasts (NFs) and cancer-associated fibroblasts (CAFs) were isolated and characterized from normal control and prostate cancer specimens, respectively. PC3 and DU145 cells, and the corresponding enzalutamide resistant counterparts, PC3-EnzR and DU145-EnzR, were co-cultured with NFs or CAFs to evaluate the effects of TME in driving enzalutamide resistance. Cell viability of prostate cancer cells was examined by MTT assay. The study also utilized recombinant human neuregulin-1 (NRG1) protein and siRNA to modulate NRG1 expression in CAFs. RT-qPCR, Western blot, and ELISA were employed to assess gene and protein expressions related to the NRG1-HER3 signaling pathway and its association with enzalutamide resistance. CAFs significantly promoted cell growth and enzalutamide resistance of PC3-EnzR and DU145-EnzR cells through substantial increased secretion of NRG1 by CAFs. Co-culturing enzalutamide-resistant prostate cancer cells (PC3-EnzR and DU145-EnzR) with CAFs further enhanced enzalutamide resistance, as evidenced by elevated IC50 values. Inhibition of NRG1 in CAFs attenuated their impact on enzalutamide resistance, providing insight into the role of NRG1 in mediating the crosstalk between CAFs and prostate cancer in the context of enzalutamide resistance. This study elucidates the pivotal role of CAF-secreted NRG1 in promoting enzalutamide resistance in prostate cancer, providing valuable insights for developing targeted therapeutic strategies to overcome resistance in advanced prostate cancer.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 10","pages":"4830-4840"},"PeriodicalIF":3.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560826/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646510","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tumor size, HER-2 status, CA125, CEA, SII, and PNI: key predictors of pathological complete response in LABC patients.","authors":"Xinyi Guo, Ronglan Wen, Liangfei Yu, Hui Lin","doi":"10.62347/YAWK6271","DOIUrl":"10.62347/YAWK6271","url":null,"abstract":"<p><p>The objective of this study was to identify characteristic factors for pathological complete response (pCR) in patients with locally advanced breast cancer (LABC) undergoing surgery and neoadjuvant chemotherapy (NACT). We retrospectively collected pathological data from 237 LABC patients treated in Affiliated Fuzhou First Hospital of Fujian Medical University from January 2010 to June 2021 and divided them into a training group (n = 166) and a validation group (n = 71) in a 7:3 ratio. A predictive model for pCR was established through logistic regression analysis and evaluated using the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Significant differences between the pCR and non-pCR groups were observed in tumor size (P = 0.001), T stage (P = 0.003), estrogen receptor (ER) (P = 0.031), progesterone receptor (PR) (P = 0.013), human epidermal growth factor receptor 2 (HER-2) (P = 0.001), and molecular type (P = 0.001). The pCR group also had lower levels of carbohydrate antigen 19-9 (P = 0.013), cancer antigen 125 (P = 0.011), carcinoembryonic antigen (CEA) (P = 0.001), and systemic inflammatory index (SII) (P = 0.006), but a higher prognostic nutritional index (PNI) (P = 0.001) compared to the non-pCR group. There were no statistical differences in baseline data between the training and validation groups (P>0.05). Multivariate logistic regression analysis identified tumor size (P = 0.001), HER-2 (P = 0.010), CA125 (P = 0.005), CEA (P = 0.001), SII (P = 0.010), and PNI (P = 0.001) as independent risk factors for pCR. We constructed and visualized a nomogram model that included these 6 factors and developed a dynamic prediction model using the Dynamic Nomogram (DynNom) package. In a random sample of 6 patients, the probability of non-pCR reached 98.8%. The model's AUC was 0.881 in the training group, with a clinical benefit rate of 71.68% and a concordance index (C-index) of 0.881, indicating a good fit. In the validation group, the AUC was 0.722, with a clinical benefit rate of 70.2% and a C-index of 0.722, also indicating a good fit. The Delong test showed a significant difference in AUC between the two groups (P = 0.027). In conclusion, this study constructed and validated a Nomogram model based on clinical pathological features and hematological indicators, finding that higher pCR rates were associated with smaller tumor size, HER-2 positivity, lower levels of CA125 and CEA, lower SII, and higher PNI, significantly enhancing breast cancer management and offering important clinical implications.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 10","pages":"4880-4895"},"PeriodicalIF":3.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560830/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive analysis of the oncogenic potential of eukaryotic initiation factor 3M via SAAL1 interaction in lung adenocarcinoma.","authors":"Hung-Hsing Chiang, Kuan-Li Wu, Hung-Pei Tsai, Chai-Tung Ong, Chao-Yuan Chang, Yu-Yuan Wu, Tzu-Yen Shen, Jen-Yu Hung, Hsiao-Chen Lee, Ya-Ling Hsu, Ying-Ming Tsai","doi":"10.62347/JKTJ7904","DOIUrl":"10.62347/JKTJ7904","url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) carries a poor prognosis at advanced stages underscoring the need to elucidate the underlying molecular mechanisms driving its pathogenesis. This study aimed to investigate the roles of eukaryotic translation initiation factor 3 subunit M (<i>EIF3M</i>) and its associated effector, serum amyloid A-like 1 (<i>SAAL1</i>), in LUAD development and progression. Bioinformatic analyses such as TNMplot, The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO), and other public databases were used to evaluate <i>EIF3M</i> and <i>SAAL1</i> expression levels, methylation status, clinical associations, and potential transcriptional regulators across LUAD datasets. Patient samples were analyzed for <i>EIF3M</i>/<i>SAAL1</i> expression by qRT-PCR, immunohistochemistry, and ELISA. <i>EIF3M</i> and <i>SAAL1</i> were overexpressed in LUAD tumor tissues compared with normal lung tissues, correlated with advanced stage, nodal metastasis, and poor survival outcomes. High <i>EIF3M</i>/<i>SAAL1</i> levels associated with increased cell proliferation, epithelial-mesenchymal transition, metastasis, and regulatory T cell dysfunction based on gene set enrichment analysis (GSEA). Mechanistically, <i>EIF3M</i>/<i>SAAL1</i> upregulation was linked to promoter hypomethylation, and transcriptionally regulated by JMJD1C, via hTFtarget prediction. The <i>EIF3M</i>/<i>SAAL1</i> promote oncogenic cellular programs and immunosuppressive microenvironments that conferred unfavorable prognosis. These findings nominate EIF3M/SAAL1 as potential therapeutic targets and biomarkers in LUAD.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 10","pages":"4817-4829"},"PeriodicalIF":3.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockdown of EPS8 expression attenuates the proliferation of enzalutamide-resistant prostate cancer cells.","authors":"Wei-Lun Huang, Sih-Han Chen, Richard Chen-Yu Wu, Hsing-Cha Mai, Chun-Hsien Wu, Pei-Fang Hsieh, See-Tong Pang, Victor Chia-Hsiang Lin","doi":"10.62347/YQWJ7498","DOIUrl":"10.62347/YQWJ7498","url":null,"abstract":"<p><p>Androgen deprivation therapies, the key treatment options for prostate cancer, have shown resistance and disease progression in many patients receiving these treatments. Therefore, it is crucial to identify new targetable pathways. Epidermal growth factor receptor pathway substrate 8 (Eps8) is one such potential target. Although this pathway is associated with the progression of various cancers, studies on the role of Eps8 in prostate cancer remain limited. This study investigated the role of Eps8 in prostate cancer. The LNCaP cell line and enzalutamide-resistant LNCaP (LNCaP Enz-R) cell lines were utilized for the investigation. Overexpression of Eps8 was observed in the LNCaP Enz-R cells. Transfecting pCMV-EPS8 also increased the levels of epithelial-to-mesenchymal transition (EMT), cell proliferation, and cell viability in both cell lines. Conversely, knockdown of Eps8 expression decreased the levels of EMT, cell proliferation, and cell viability in both cell lines. Furthermore, EPS8-induced EMT activation could be reversed by suppressing the Ras/JAK/PI3K signaling pathway. In vivo animal study also confirmed the crucial role of Eps8 expression in prostate cancer progression. Therefore, we suggest that targeting Eps8 by knocking down its expression is promising as a therapeutic approach for prostate cancer treatment.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 10","pages":"4717-4730"},"PeriodicalIF":3.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560819/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646483","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preoperative prognostic nutritional index and systemic immune inflammation index for predicting the efficacy and survival time of patients with osteosarcoma undergoing neoadjuvant chemotherapy combined with surgery.","authors":"Jin Jiang, Tingxiao Zhao, Longtao Yao, Tao Zhang, Lichen Ji, Wei Zhang, Yanlei Li, Jinlong Tian, Xiaoyan Ding, Yongqin Lin, Liang Han","doi":"10.62347/MHXS8480","DOIUrl":"10.62347/MHXS8480","url":null,"abstract":"<p><strong>Objective: </strong>To explore the value of preoperative prognostic nutritional index (PNI) and systemic immune inflammation index (SII) for predicting the efficacy and prognosis of patients with osteosarcoma undergoing neoadjuvant chemotherapy (NACT) combined with surgery.</p><p><strong>Methods: </strong>A retrospective study was conducted on patients with osteosarcoma undergoing NACT combined with surgery in Sun Yat-sen University Cancer Center from January 2017 to May 2019. The patients were grouped into a remission group (pCR group, 85 patients) and a non-remission group (non-pCR, 79 patients), according to the treatment efficacy. The pathological data as well as clinical data were collected from patients, which were subsequently employed for statistical analysis to determine the factors affecting the efficacy of the treatment. The diagnostic value of PNI and SII for predicting the efficacy were assessed through following up the patients for 5 years to observe their overall survival rate. COX regression analysis was leveraged to identify risk factors affecting the survival time. The impact of different PNI and SII levels on the survival time was observed.</p><p><strong>Results: </strong>Multivariate regression analysis showed that factors including Enneking stage, PNI level and SII level were in association with poor efficacy after NATC combined with surgery. The mortality within 5 years was higher and the 5-year overall survival rate was lower in the non-pCR group than those in the pCR group (both P < 0.05). The COX regression analysis indicated that PNI and SII levels were risk factors for poor prognosis in patients with osteosarcoma following NACT combined with surgery. Further analysis showed that patients with low PNI and high SII levels had a lower 5-year survival rate (P < 0.05).</p><p><strong>Conclusion: </strong>Enneking stage, PNI, and SII levels were risk factors for poor efficacy in patients with osteosarcoma after NACT combined with surgery. Patients whose PNI level was low and SII level was high presented poor prognosis following the treatment.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 10","pages":"4946-4955"},"PeriodicalIF":3.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560818/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cell-based assay to detect small molecules restoring levels of let-7 miRNAs.","authors":"Sirinapa Szewczyk, Brian Buckley, Mikhail Chernov, Xinjiang Wang, Shilpa Pathak, Herman Yeger, Kristopher M Attwood, Renae Holtz, Christine B Ambrosone, Michael J Higgins","doi":"10.62347/MBLD9480","DOIUrl":"10.62347/MBLD9480","url":null,"abstract":"<p><p>Blockage of <i>let-7</i> miRNA biogenesis by LIN28, or other mechanisms, results in derepression of <i>let-7</i> target genes, some of which are oncogenic (e.g., <i>MYCN</i>) potentially contributing to tumor progression and drug resistance. We have developed a cell-based assay to identify small molecules that increase levels of mature functional let-7 miRNAs by inhibiting the function of Lin28B protein or by other means. This system consists of a reporter gene (GFP) regulated by the tTR-KRAB repressor protein which in turn is regulated by processed <i>let-7</i> miRNAs. Using this system, we screened approximately 4000 small molecules and identified more than a dozen compounds capable of augmenting levels of mature <i>let-7</i> miRNAs. Among those compounds, Kenpaullone and BIO were shown to increase <i>let-7</i> miRNA levels with consequent suppression of MYCN protein in neuroblastoma cell lines. This novel strategy provides an additional cell-based assay for candidate cancer drug screening in a high throughput setting and will facilitate the identification of anti-cancer drugs. Moreover, this assay could be used to screen shRNA and CRISPR libraries to identify novel components of the LIN28-<i>let-7</i> axis which may provide new therapeutic targets.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 10","pages":"4772-4787"},"PeriodicalIF":3.6,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11560832/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}