American journal of cancer research最新文献

{"title":"The effect of body mass index at diagnosis on survival of patients with squamous cell head and neck carcinoma.","authors":"Roberta Pastorino, Denise Pires Marafon, Nicolò Lentini, Ilda Hoxhaj, Adriano Grossi, Luca Giraldi, Antonella Rondinò, Gabriella Cadoni, Jerry Polesel, Diego Serraino, Carlo La Vecchia, Werner Garavello, Cristina Canova, Lorenzo Richiardi, Jolanta Lissowska, Tamas Pandics, Tom Dudding, Andy Ness, Steve Thomas, Miranda Pring, Karl Kelsey, Michael McClean, Patrick Bradshaw, Zuo-Feng Zhang, Hal Morgenstern, Laura Rozek, Gregory Wolf, Andrew Olshan, Geoffrey Liu, Rayjean Hung, Marta Vilensky, Marcos Brasilino de Carvalho, Rossana Verónica Mendonza López, Victor Wunsch-Filho, Paolo Boffetta, Mia Hashibe, Yuan-Chin Amy Lee, Stefania Boccia","doi":"10.62347/UUXK7608","DOIUrl":"10.62347/UUXK7608","url":null,"abstract":"<p><p>The aim of this study is to investigate the prognostic role of body mass index (BMI) on survival from head and neck cancer (HNC). We performed a pooled analysis of studies included in the International Head and Neck Cancer Epidemiology consortium. We used Cox proportional hazards models to estimate the adjusted hazard ratios (HR) for overall survival and HNC-specific survival, and we stratified the results according to cancer site. The study included 10,177 patients from 10 studies worldwide. Underweight patients had lower overall survival (HR=1.69, 95% CI: 1.31-2.19) respect to those having normal weight with consistent results across the HNC sites. Overweight and obese patients had a favourable HNC-specific survival (HR=0.77 (95% CI: 0.70-0.84) and HR=0.80 (95% CI: 0.76-0.84), respectively), with heterogenous results according to HNC site. Our findings show that high BMI values at cancer diagnosis improved the survival rates in patients with HNC, especially among smokers. This association may be explained by residual confounding, reverse causation, and collider stratification bias, but may also suggest that a nutritional reserve may help patients survive HNC cancer.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5411-5426"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805869","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":"Reproductive factors and expression of stem cell markers in women with incident benign breast disease.","authors":"Tengteng Wang, Yujing J Heng, Brian R Sardella, Bernard Rosner, Rulla M Tamimi, Lusine Yaghjyan","doi":"10.62347/KLAC9365","DOIUrl":"10.62347/KLAC9365","url":null,"abstract":"<p><p>Reproductive factors are well-established risk factors for breast cancer. The prevailing hypothesis suggested that stem cell changes may be the key underlying mechanisms, but epidemiological evidence has been notably scarce. Herein we examined the relationship between reproductive risk factors and the expression of well-established stem cell markers CD44, CD24, and ALDH1A1 in benign breast biopsy non-cancerous samples. Our study included 735 participants from the Nurses' Health Study II who were diagnosed with biopsy-confirmed incident benign breast disease (BBD). Reproductive history and other BBD/breast cancer risk factors were measured from self-reported biennial questionnaires. Immunohistochemistry was performed on breast tissue microarrays from normal terminal ductal-lobular units (TDLU) cores. Marker expression in epithelium and stroma was quantified using semi-automated image analysis. The generalized linear regression was used to examine the associations of reproductive factors with the positive expression of CD44, CD24, and ALDH1A1, adjusted for known breast cancer risk factors. Age at first birth ≥30 years old (vs. <25 years) was associated with lower ALDH1A1 expression in the epithelium (β for ≥30 vs. <25 years = -0.30, 95% CI -0.57; -0.03, p-trend = 0.03). Parity, breastfeeding, age at menarche, and the time interval between menarche and age at first birth were not associated with the expression of any of the three markers in epithelium or stroma. These findings suggest age at first birth may influence the ALDH1A1 expression in breast tissue. Our study added to the very limited evidence regarding the potential impact of reproductive factors on breast stem cell markers.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5434-5445"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626268/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805854","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":"Sotorasib inhibits ubiquitination degradation of TXNIP and suppresses glucose metabolism in <i>KRAS^G12C</i> mutant bladder cancer.","authors":"Zhi-Rong Zhang, Min-Qi Liu, Yang Ji, Di Xiao, Wei-Fan Wang, Xiao-Chen Zhou, Ling-Hui Wang, Duo Li, Hui Zou, Xiao-Ping Yang","doi":"10.62347/XEBR7848","DOIUrl":"10.62347/XEBR7848","url":null,"abstract":"<p><p>Bladder cancer is the most common malignant tumor of the urinary system. Currently, treatment strategies for bladder cancer remain limited, highlighting the urgent need to explore novel therapeutic approaches. Sotorasib, the first successful small molecule drug targeting KRAS, has been approved for treating non-small cell lung cancer (NSCLC), but it has not yet been studied in bladder cancer. Additionally, glucose metabolism-related proteins, such as GLUT1, PKM2, and LDHA are highly expressed in most bladder cancer cell lines, promoting tumor progression. <i>KRAS^G12D</i> mutant cells exhibit enhanced glucose uptake and glycolysis. However, little is known about whether <i>KRAS^G12C</i> mutant cells exhibit enhanced glucose metabolism. Various techniques, including glucose and lactate analysis, Seahorse assay, western blot, qRT-PCR, and immunofluorescence, were used to investigate whether Sotorasib can inhibit glucose metabolism in bladder cancer cells. The results demonstrated that Sotorasib significantly inhibited glucose metabolism in <i>KRAS^G12C</i> mutant bladder cancer, both <i>in vitro</i> and <i>in vivo</i>, but not in wild-type bladder cancer. Furthermore, Sotorasib's inhibition of glucose metabolism was associated with suppressing the degradation of thioredoxin-interacting protein (TXNIP), a negative regulator of glucose metabolism. Additionally, Sotorasib increased TXNIP expression by regulating the RAS/RAF/ERK axis. This study uncovers the mechanism by which Sotorasib inhibits glucose metabolism in <i>KRAS^G12C</i> mutant bladder cancer cells and suggests a potential therapeutic benefit for the treatment of <i>KRAS^G12C</i> mutant bladder cancer.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5251-5268"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626273/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805864","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":"The role of novel adipokines in hepatocellular carcinoma progression: a mini review.","authors":"Panpan Hu, Dezhi Guo, Keyun Cao, Tianying Xu","doi":"10.62347/PZDM1736","DOIUrl":"10.62347/PZDM1736","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC), which originates from hepatocytes, accounts for the majority of primary liver cancers. Globally, HCC ranks among the most common cancers and is a leading cause of cancer-related deaths. Obesity, a growing health issue worldwide, is increasingly recognized as a critical risk factor for HCC, influenced by both epidemiological and clinical factors. Adipokines, secreted by adipocytes, have been shown to play pivotal roles in the tumor microenvironment, affecting cancer progression, metastasis, and resistance to therapies through various signaling mechanisms. Despite inconsistencies in certain findings, a substantial body of research supports the significant role of adipokines in HCC development. This review focuses on exploring newly identified adipokines and their mechanisms in HCC, with the goal of uncovering potential therapeutic targets for improved management and treatment strategies.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5471-5485"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626281/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805891","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":"Adjuvant osimertinib therapy guided by ctDNA-assessed MRD in resected EGFR-mutated stage IA-IIA non-small-cell lung cancer: a randomized clinical trial study protocol.","authors":"Kun Wang, Junrui Ma, Wei Luo, Qing Yin, Xugang Zhang, Yize Li, Hushan Zhang","doi":"10.62347/IFRH7248","DOIUrl":"10.62347/IFRH7248","url":null,"abstract":"<p><strong>Aims: </strong>We investigate the value of postoperative minimal residual disease (MRD) detection using circulating tumor DNA (ctDNA) in guiding adjuvant therapy for patients with potentially high recurrence risk in non-small cell lung cancer (NSCLC) due to the presence of MRD.</p><p><strong>Patients and methods: </strong>A randomized controlled trial will enroll stage IA-IIA NSCLC patients with Epidermal Growth Factor Receptor (EGFR) mutation and negative resection margins to evaluate the clinical value of MRD in guiding adjuvant osimertinib. That is, if the patient's peripheral blood does not show ctDNA (negative) after next generation sequencing (NGS) testing, postoperative observation and follow-up are sufficient. Conversely, if ctDNA is positive, the patient will be randomly assigned to two groups and receive adjuvant treatment with osimertinib or observation and follow-up. In total 1068 postoperative patients should be recruited, finally, 32 MRD positive patients were divided into a treatment group or an observation group.</p><p><strong>Primary endpoint: </strong>progression-free survival (PFS). Secondary endpoints: 2- and 5-year PFS rates, regimen safety, and tolerability. Exploratory indicator in the MRD-positive group: ctDNA clearance rate at 12 and 24 months.</p><p><strong>Results and conclusions: </strong>This study provides crucial insights into therapy guidance for EGFR-mutated NSCLC patients with MRD, potentially enhancing patient outcomes.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5427-5433"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626269/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805973","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":"Efficacy and safety of immune checkpoint inhibitors in heavily pretreated patients with microsatellite stable metastatic colorectal cancer: a real-world retrospective study.","authors":"Wensi Zhao, Yongshun Chen","doi":"10.62347/KAFY8529","DOIUrl":"10.62347/KAFY8529","url":null,"abstract":"<p><p>Immune checkpoint inhibitor (ICI) has changed the situation of anti-tumor therapy. Several phase I/II clinical trials explored ICI-based combinations in microsatellite stable (MSS) metastatic colorectal cancer (mCRC) with mixed outcomes. However, real-world data regarding ICI-based combinations in this population is lacking. This retrospective study aimed to evaluate the efficacy and safety of ICI in MSS mCRC patients in third-line or above setting. A total of 143 eligible patients who received third-line or above ICI monotherapy or ICI-based combinations at the Cancer Center of Renmin Hospital of Wuhan University from June 2019 to April 2024 were included in this study. The primary endpoints were real-world median progression-free survival (PFS) and overall survival (OS), and the secondary endpoints included objective response rate (ORR), disease control rate (DCR), safety and prognostic analyses. Results showed that the median PFS was 4.6 months, and the median OS was 11.8 months, with an ORR of 11.2% and a DCR of 72.7%. ICI plus small molecule tyrosine kinase inhibitors have become the most popular combination for MSS mCRC patients at third-line or above setting with a median PFS of 4.4 months and OS of 10.1 months. The subgroup of patients with liver metastasis had worse clinical outcomes and liver metastasis was an independent prognostic factor for PFS (HR = 2.35, 95% CI, 1.54-3.59; <i>P</i> = 0.000) and OS (HR = 1.77, 95% CI, 1.06-2.96; <i>P</i> = 0.030). Forty-eight patients received cross-line ICI and obtained significantly improved OS (15.8 months vs 10.2 months; HR = 0.59, 95% CI, 0.38-0.89; <i>P</i> = 0.017). No new safety concerns were detected. Grade 3/4 treatment-related adverse events were generally controllable, with an incidence of 39.9%. To conclude, ICI-based combinations provide survival benefits for these heavily pretreated MSS mCRC patients with manageable safety, which is worthy of further study.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5378-5388"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626271/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805606","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":"Artificial intelligence algorithms for real-time detection of colorectal polyps during colonoscopy: a review.","authors":"Meng-Yuan Nie, Xin-Wei An, Yun-Can Xing, Zheng Wang, Yan-Qiu Wang, Jia-Qi Lü","doi":"10.62347/BZIZ6358","DOIUrl":"10.62347/BZIZ6358","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is one of the most common cancers worldwide. Early detection and removal of colorectal polyps during colonoscopy are crucial for preventing such cancers. With the development of artificial intelligence (AI) technology, it has become possible to detect and localize colorectal polyps in real time during colonoscopy using computer-aided diagnosis (CAD). This provides a reliable endoscopist reference and leads to more accurate diagnosis and treatment. This paper reviews AI-based algorithms for real-time detection of colorectal polyps, with a particular focus on the development of deep learning algorithms aimed at optimizing both efficiency and correctness. Furthermore, the challenges and prospects of AI-based colorectal polyp detection are discussed.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5456-5470"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805924","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":"Integration of bioinformatics analysis reveals ZNF248 as a potential prognostic and immunotherapeutic biomarker for LIHC: machine learning and experimental evidence.","authors":"Lifang Weng, Zhicheng Cheng, Zhisong Qiu, Jin Shi, Libin Chen, Chunsheng He, Lijuan Wang, Feng Jin","doi":"10.62347/CDUS5096","DOIUrl":"10.62347/CDUS5096","url":null,"abstract":"<p><p>Liver hepatocellular carcinoma (LIHC) is a major contributor to cancer-related mortality worldwide, posing substantial diagnostic and therapeutic challenges. Although zinc finger proteins (ZNFs) are known to play a role in LIHC, the specific function of ZNF248 remains poorly understood. In this study, we analyzed genomic and clinical data from The Cancer Genome Atlas (TCGA) to elucidate the role of ZNF248 through differential expression analysis, bioenrichment, immune response correlation, and drug sensitivity evaluation. Machine learning was employed to identify prognostic signatures derived from ZNF248, which were further validated using Receiver Operating Characteristic (ROC) analysis. Functional assays, including Western blot and rescue experiments, were performed to assess the impact of ZNF248 on the PI3K/AKT signaling pathway. Our results demonstrate that ZNF248 is significantly overexpressed in LIHC patients and is associated with poor prognosis. Bioenrichment analysis revealed activation of oncogenic pathways, and elevated ZNF248 expression correlated with increased immune cell infiltration and enhanced immune scores, thereby influencing both immunotherapy response and drug sensitivity. Functional assays further confirmed that ZNF248 promotes LIHC progression and invasion, while silencing ZNF248 inhibited the PI3K/AKT pathway - a phenomenon reversible by the AKT activator SC79. These findings suggest that ZNF248 contributes to LIHC progression through the PI3K/AKT pathway and may represent a novel immunotherapeutic target and prognostic biomarker for LIHC.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5230-5250"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805681","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":"RBM15 increase tumor-infiltrating CD4+ T cell in ESCC <i>via</i> modulating of PLOD3.","authors":"Xuyang Lin, Xiao Han, Wubi Zhou, Xiaoxia Gong, Yu Zhou, Qilong Wang, Chengwan Zhang","doi":"10.62347/IDCP2061","DOIUrl":"10.62347/IDCP2061","url":null,"abstract":"<p><strong>Background: </strong>Collagen, a primary protein component of the extracellular matrix (ECM), undergoes a notable series of alterations concomitant with the growth of the tumor. Procollagen-lysine,2-oxoglutarate 5-dioxygenase 3 (PLOD3) is involved in the synthesis of collagen and has been associated with a variety of cancers. However, it is unclear how PLOD3 functions in esophageal squamous cell carcinoma (ESCC).</p><p><strong>Methods: </strong>Differentially expressed genes between ESCC and adjacent normal tissues were identified using proteomic and transcriptomic analyses. These genes were then subjected to survival analysis to identify prognostic markers. Immune cell infiltration in the two subgroups was evaluated. Spearman's correlation analysis was performed to examine the correlation between PLOD3 and RBM15 expression in TCGA-ESCC database. shRNA-mediated approach was used to knockdown RBM15 in ESCC cells. The effects of RBM15 knockdown on PLOD3 expression were assessed by real-time PCR and Western blot. Moreover, COX algorithm was employed to construct a prognostic signature.</p><p><strong>Results: </strong>PLOD3 was found to be highly expressed in ESCC patients and correlated with a favorable prognosis. Immune cell infiltration estimation indicated tumor-infiltrating CD4+ T cell was increased in PLOD3-high group. Correlation analysis revealed that PLOD3 was associated with RBM15 and was closely related to CD4+ T cell infiltration. Moreover, loss-of-function approaches showed that depletion of RBM15 attenuated PLOD3 expression in ESCC cells. Following univariate and multivariate Cox regression analyses, PLOD3 and RBM15 were identified as a two-gene prognostic signature for ESCC.</p><p><strong>Conclusion: </strong>RBM15 enhances tumor-infiltrating CD4+ T Cell abundance in ESCC by regulating PLOD3. Two new independent prognostic factors, PLOD3 and RBM15, may be useful in predicting the prognosis of ESCC.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5486-5503"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805848","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":"Anti-carcinogenic effects and mechanisms of actions of <i>Citrus limon</i> fruit peel hydroethanolic extract and limonene in diethylnitrosmine/2-acetylaminofluorene-induced hepatocellular carcinoma in Wistar rats.","authors":"Rania S Ezzat, Adel Abdel-Moneim, Khairy Ma Zoheir, Eman E Mohamed, Howida S Abou-Seif, Mohamed Hefnawy, Osama M Ahmed","doi":"10.62347/FOYI6658","DOIUrl":"10.62347/FOYI6658","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the third most common cause of cancer death and disability in the world. Citrus species and their constituents have many biological activities including antioxidant, anti-inflammatory and anti-carcinogenic properties. This study aimed to assess the anti-carcinogenic effects and postulate the possible mechanisms of action for Citrus limon fruit peel hydroethanolic extract (CLFPHE) and limonene in diethylnitrosamine (DEN)/2-acetylaminofluorene (2AAF)-induced HCC in male Wistar rats. For analysis and characterization of CLFPHE, gas chromatography-mass spectrum (GC-MS) and high performance liquid chromatography (HPLC) methods were applied. A HCC was elaborated by DEN intraperitoneal injection (150 mg/kg/week) for two weeks followed by oral delivery of 2AAF (20 mg/kg) four times a week for three weeks. The DEN/2AAF-administered rats were treated with CLFPHE (50 mg/kg) and limonene (20 mg/kg) by oral gavage every other day for 24 weeks. CLFPHE and limonene significantly attenuated the harmful effects of DEN on liver function. Histopathological analysis confirmed that both treatments inhibited DEN/2AAF-induced tumorigenesis in association with the suppression of serum tumor markers including AFP, CEA, and CA19.9 and liver proliferator indicator (Ki-67). Moreover, CLFPHE and limonene prevented the oxidative stress and enhanced the antioxidant defenses in DEN/2AAF-administered rats. These ameliorations were manifested by decreases in liver lipid peroxidation, increases in GSH, SOD and GPx levels and upregulation of Nrf2. The treatments also abated inflammation by suppressing TNF-α and IL-1β levels and IL-8 and NF-κB expression. CLFPHE and limonene substantially decreased hepatic BCL-2, IQGAP1, IQGAP3, HRAS, KRAS and Ki-67 while they elevated BAX, P53, PDCD5 and IQGAP2 expressions. Our findings suggest that CLFPHE and limonene may abate HCC development via enhancement of apoptotic, antioxidant, cell anti-proliferatory and anti-inflammatory effects.</p>","PeriodicalId":7437,"journal":{"name":"American journal of cancer research","volume":"14 11","pages":"5193-5215"},"PeriodicalIF":3.6,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11626260/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142805923","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}