NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 (NDUFS3) is the core subunit of the respiratory chain complex I (CI). We found NDUFS3 were abnormally elevated in human melanoma and promoted melanoma proliferation. Furthermore, NDUFS3 could promote the oxidative phosphorylation (OXPHOS) and the pentose phosphate pathway (PPP), as well as attenuated glycolysis. As NDUFS3-mediated the metabolic changes of OXPHOS and glucose metabolism, melanoma cells produced more ATP, resulting in the inhibition of AMP kinase (AMPK). AMPK induced phosphoribosyl pyrophosphate synthetase1 (PRPS1) phosphorylation, which resulted in suppressed PRPS1 activity. Briefly, the NDUFS3-AMPK-PRPS1 signaling axis coupled OXPHOS, glucose metabolism, and purine nucleotide biosynthesis to regulate melanoma proliferation. Our study highlighted an unrecognized role for NDUFS3 in melanoma, which might be used as a potential therapeutic target for the treatment of this type of cancer.

Breast cancer (BC) remains a leading cause of cancer-related mortality in women worldwide. Through online data mining, we identified the significant upregulation of the RNA-binding protein La Ribonucleoprotein 1 (LAR1) in BC. Functionally, LAR1 knockdown impeded S-phase entry, migration, and invasion of BC cells in vitro. Consistently, it markedly suppressed tumor growth and liver metastasis in BALB/c nude mice. Mechanistically, LAR1 promoted AKT phosphorylation and IκBα degradation, leading to NF-κB activation, with the NF-κB inhibitor PDTC rescuing LAR1's effects. Integrated analysis of transcriptome and previous data of LAR1-mRNA interactome revealed Apolipoprotein C1 (APOC1) as a key target. LAR1 bound to the APOC1 3'-UTR to stabilize its mRNA, and APOC1 overexpression counteracted the effects of LAR1 knockdown. In conclusion, our study defines the LAR1-APOC1-NF-κB axis as a crucial driver of BC progression, offering a promising therapeutic strategy for BC treatment.

Nucleotide-binding oligomerization domain 2 (NOD2) is an immune sensor crucial for eliciting the innate immune responses. Nevertheless, discrepancies exist regarding the effect of NOD2 on different types of cancer. This study aimed to investigate these function of NOD2 in melanoma and its underlying mechanisms. We have validated the tumor suppressor effect of NOD2 in melanoma. NOD2 inhibited the proliferation of melanoma cells, hindering their migration and invasion while promoting the onset of apoptosis. Our study showed that NOD2 expression is closely related to pyrimidine and folate metabolism. NOD2 inhibits thymidylate synthase (TYMS) expression by promoting K48-type ubiquitination modification of TYMS, thereby decreasing the resistance of melanoma cells to 5-fluorouracil (5-FU) and capecitabine (CAP). TYMS was identified to form a complex with Polo-like Kinase 1 (PLK1) and activate the PLK1 signaling pathway. Furthermore, we revealed that the combination of the PLK1 inhibitor volasertib (BI6727) with 5-FU or CAP had a synergistic effect repressing the proliferation, migration, and autophagy of melanoma cells. Overall, our research highlights the protective role of NOD2 in melanoma and suggests that targeting NOD2 and the TYMS/PLK1 signaling axis is a high-profile therapy that could be a prospect for melanoma treatment.

Myc-associated Zinc-finger Protein (MAZ) has been implicated in the malignant progression of various tumors. However, its expression and functional relationship of MAZ in melanoma have not been previously investigated. This study confirms elevated expression of MAZ in melanoma, correlating with poor patient prognosis. Furthermore, our findings demonstrate that MAZ enhances melanoma progression by promoting proliferation, migration and invasion. It is worth noting that we found that MAZ can target and regulate the transcription of NADH dehydrogenase [ubiquinone] iron-sulfur protein 3 (NDUFS3), a core subunit of mitochondrial complex I, to enhance mitochondrial metabolism and thus promote malignant progression of melanoma. Predictive modeling indicates that the co-expression of MAZ and NDUFS3 could serve as a potential prognostic marker for melanoma patients. Myc-associated Zinc-finger Protein MAZ regulates the transcription of NDUFS3, a core subunit of mitochondrial complex I, to enhance mitochondrial metabolism, thus promoting malignant progression of melanoma.

Long noncoding RNAs (lncRNAs) play crucial roles in melanoma initiation and development, serving as potential therapeutic targets and prognostic markers for melanoma. lncRNA survival-associated mitochondrial melanoma-specific oncogenic noncoding RNA (SAMMSON) is upregulated in many types of human cancers. However, the functions of SAMMSON in melanoma have not been fully elucidated. This study is aimed at investigating the expression and functions of SAMMSON in melanoma development. Bioinformatics analysis was performed to determine the expression of SAMMSON and its correlation with the 10-year overall survival (OS) in melanoma patients. Cell proliferation, migration, invasion, and tumorigenesis were detected by MTT, colony formation, Transwell assays, and mouse xenograft model. The expression of cell cycle-related factors, epithelial-to-mesenchymal transition (EMT) makers, and matrix metalloproteinases (MMPs) was assessed by RT-qPCR and western blotting analysis. The results demonstrated that SAMMSON expression was upregulated in melanoma tissues and cells, and lower SAMMSON expression was correlated with longer 10-year OS. SAMMSON knockdown decreased the proliferation, migration, and invasion of melanoma cells by regulating the expression of proliferation-related genes, EMT factors, and MMPs, respectively. Additionally, Forkhead box protein A2 (FOXA2) was confirmed to be a target of SAMMSON, and the biological effects induced by FOXA2 overexpression were similar to those induced by SAMMSON silencing in melanoma cells. Further studies showed that SAMMSON downregulated FOXA2 expression in melanoma cells by modulating the EZH2/H3K27me3 axis. Taken together, our data indicate that SAMMSON plays an important role in melanoma progression and can be a valuable biomarker and therapeutic target in melanoma.

目的 探讨透明细胞乳头状肾细胞肿瘤(ccpRCT)的临床病理学特点.方法 对9 例ccpRCT的临床表现、大体及组织学特征、免疫组化进行分析,并复习相关文献.结果 9 例患者中男7 例,女2 例,年龄47～67 岁,平均年龄56岁,3 例患者有肉眼血尿,其余为体检时发现肾占位;9 例患者中6 例发生在左肾,3 例发生在右肾;6 例行肾部分切除术,其余为根治性肾全切术.大体上肿块大小1～6 cm;镜下大部分以乳头状结构为主,少数可见囊性改变和腺管状结构,被覆立方上皮细胞,胞浆空亮透明,细胞核圆形或卵圆形,核膜规则,染色深,核仁不明显.免疫组化:9 例均表达 CK7、CAIX、CKL、CKH及VIM.结论 ccpRCT是2022 年新更名的肾肿瘤实体,总体生物学行为表现为惰性,需正确区分该肿瘤与其他肾恶性肿瘤.

1 病例 患者女, 48岁, 因"体检发现肾血管瘤"入院, 无腹痛腹胀等明显异常, 患者入院前半月在外院就诊行腹部 CT 检查提示: 左肾血管平滑肌瘤, 故于2020 年2 月3 日入我院行进一步治疗,入院行腹部增强CT检查示: 左肾上方见一大小约10. 2 × 14. 7 cm的混杂密度团块影, 其内见骨骼及脂肪成分, 考虑畸胎瘤伴周围脏器受压变形, 见图1.尿常规见红细胞、白细胞、上皮细胞均高于正常水平, 完善相关辅助检查后, 行剖腹探查发现, 肿块位于左肾周, 表面光滑, 切除肿块后行病理检查.

Purpose High-risk human papillomavirus (HR-HPV)-positive but cytology-negative cervical cancer screening results are not uncommon. This study aimed to investigate colposcopy's accuracy and diagnostic value in patients with cytology-negative HR-HPV-positive screening results. Methods This retrospective study included patients with HR-HPV-positive cytology-negative screening results who underwent electronic colposcopy with acetic acid and multi-point cervical biopsy, HPV typing (24 HPV subtypes), and quantitative HPV detection. Results Among 229 patients, 130 had chronic cervicitis, and 99 had cervical lesions (CIN1, n = 37; CIN2/3, n = 55; invasive carcinoma, n = 7). Using colposcopy as a reference, the cervical cytology false-negative rate was 43.2% (99/229). Colposcopy was more accurate in patients with HR-HPV16/18 or high viral loads. Multivariable analyses showed HPV viral load and childbearing history were the independent factors affecting the accuracy of colposcopy (P < 0.05). Conclusion Colposcopy in HR-HPV-positive cytology-negative patients has a moderate diagnostic accuracy. The type of cervical transformation zone and HPV viral load are independent factors affecting the accuracy of colposcopy-based diagnosis.

Background: Breast cancer is the most common malignancy and the leading cause of cancer death among women. Glycoprotein V (GP V) is involved in thrombin-induced platelet activation and in other platelet responses. However, its roles and underlying mechanisms in the pathogenesis of breast cancer are still unclear. This study aimed at assessing GP V expression in breast cancer, its subsequent effects on cancer cell apoptosis, proliferation, invasion, and migration, and the underlying molecular mechanisms. Methods: GP V mRNA expression was analysed in total RNA samples obtained from tumor and adjacent normal tissue of 41 breast cancer patients and cell lines (MDA-MB-231, MCF-7 and MCF-10A). The correlation between the expression of GP V and clinicopathological features was analyzed by immunohistochemical (IHC) staining. Stable knockdown and overexpression MDA-MB-231 cell lines were generated by using the lentiviral system. Then, the cells were harvested for CCK-8 assay, flow cytometry, scratch healing experiments, and western blotting. Two samples each from the Stable knockdown and control groups were used for transcriptome sequencing and pathway analysis. Finally key molecules associated with the related signaling pathways were analyzed by RT-PCR and western blot. Results: The results showed that the mRNA (P<0.0001) and protein expression (P<0.001) of GP V in the breast cancer tissues was significantly increased compared with in the adjacent non-tumor tissues. The protein and mRNA expression of GP V were significantly higher in MDA-MB-231 and MCF-7cell lines compared with human normal breast epithelial cells (MCF-10A) (P<0.01). GP V expression was positively correlated with higher histological grade and advanced TNM stage. (P<0.05), but was not related to gender, age, menopausal status, tumor size, vascular invasion, ER, PR, Ki-67 and lymph node metastasis (P>0.05). CCK-8 assay showed that cell viability was enhanced after GP V upregulation compared to the control group (P<0.05). The in vitro scratch assay showed that the number of GP-V-overexpressing cells migrating to the scratch area was significantly higher than that of the control group at 24 h and 48 h, respectively (P<0.001). Flow cytometric analysis demonstrated there was no significant difference in cell cycle distribution and apoptosis. Differential gene expression analysis showed 13 significantly down- and 141 upregulated mRNAs. The mRNA expression levels of PI3K and AKT were significantly increased after GP V upregulation compared with those in the control group (P<0.001). N-cadherin, Vimentin and MMP2/9 were up-regulated after GP V upregulation compared with those in the control group (P<0.05).Conclusion: GP5 is highly expressed in breast cancer tissues and may play an important role as a cancer-promoting gene in breast cancer. The high expression of GP5 was significantly associated with higher nuclear grade, TNM stage and Her-2 negativity. GP5 can promote the proliferation, invasion, and metastasis of breast cancer cells. GP5 may promote the proliferation, invasion, and metastasis by activating PI3K/AKT signaling pathway to upregulate MET, and is expected to become a potential target for clinic diagnosis and treatment. Citation Format: Kui Xiang, Wang Yan, Hua Yanshan, Yi Xiaojia, Zhao Chunmei, Guo Minmin. Pg5 promotes breast cancer metastasis by activatingpi3k/akt/mtor signaling pathways [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P3-06-06.

Recent evidences have shown that glycoprotein V (GP5) protein, which is initially considered as an important adhesion molecule unique to the megakaryocyte line, was also specifically expressed in malignant human breast epithelial cells. However, its expression level and function are not clear. This study aimed to reveal the abnormal expression of GP5 in breast cancer (BC), research the associations between the GP5 abnormal expression and BC progression, and explore the molecular mechanism of GP5 in BC. Immunohistochemistry, Western blot (WB), and quantitative reverse transcription-polymerase chain reaction (RT-PCR) assays were used to determine the expression patterns of GP5 in BC tissues and cells. The expression profiles of GP5 in the Cancer Genome Atlas databases were analyzed by UALCAN. The GP5 knockdown and over-expression BC cell lines were constructed and confirmed by RT-PCR and WB. Transcriptome sequencing and KEGG database were performed to screen cellular processes and signal pathways. Phosphatidylinositol 3-kinase (PI3K)/AKT pathway was verified by RT-qPCR, and epithelial-mesenchymal transition (EMT) was confirmed by WB. The results indicated GP5 was highly expressed in BC tissues and might play an important role as a cancer-promoting gene in BC. The high expression of GP5 was significantly associated with higher nuclear grade, higher TNM stage, and human epidermal growth factor receptor 2 (HER2) negativity. GP5 may promote the proliferation, invasion, and metastasis of BC cells by activating PI3K/AKT signaling pathway to up-regulate the EMT. This study provides a new idea that GP5 was expected to become a potential molecular target for early BC clinic diagnosis and treatment.

Background: Clear cell renal cell carcinoma (ccRCC) is a cell metabolic disease with high metastasis rate and poor prognosis. Our previous studies demonstrate that glucose-6-phosphate dehydrogenase (G6PD), the first and rate-limiting enzyme of the pentose phosphate pathway, is highly expressed in ccRCC and predicts poor outcomes of ccRCC patients. The aims of this study were to confirm the oncogenic role of G6PD in ccRCC and unravels novel mechanisms involving Cyclin El and MMP9 in G6PD-mediated ccRCC progression. Methods: Real-time RT-PCR, Western blot and immunohistochemistry were used to determine the expression patterns of G6PD, Cyclin El and MMP9 in ccRCC. TCGA dataset mining was used to identify Cyclin El and MMP9 correlations with G6PD expression, relationships between clinicopathological characteristics of ccRCC and the genes of interest, as well as the prognosis of ccRCC patients. The role of G6PD in ccRCC progression and the regulatory effect of G6PD on Cyclin El and MMP9 expression were investigated by using a series of cytological function assays in vitro. To verify this mechanism in vivo, xenografted mice models were established. Results: G6PD, Cyclin El and MMP9 were overexpressed and positively correlated in ccRCC, and they were associated with poor prognosis of ccRCC patients. Moreover, G6PD changed cell cycle dynamics, facilitated cells proliferation, promoted migration in vitro, and enhanced ccRCC development in vivo, more likely through enhancing Cyclin El and MMP9 expression. Conclusion: These findings present G6PD, Cyclin El and MMP9, which contribute to ccRCC progression, as novel biomarkers and potential therapeutic targets for ccRCC treatment.

目的 探讨MRI对直肠癌术前评估的价值.方法 选取84例行外科手术治疗的直肠癌患者的MRI、病理、临床资料.用卡方检验评价MRI对诊断肿瘤T分期、N分期、环周切缘(CRM)受累情况、壁外血管浸润的准确性,用配对t检验评估MRI分析病灶与齿状线位置关系的准确性.结果 MRI可较准确地评估对诊断肿瘤T分期、N分期、环周切缘受累情况、壁外血管浸润状态(P＜0.01),可大致评估低位直肠癌病灶距齿状线距离(P＞0.05).结论 MRI可较准确地评估对诊断肿瘤T分期、N分期、环周切缘受累情况、壁外血管浸润状态.受测量习惯、测量误差、肠管走行等因素的影响,MRI可大致评估病灶距齿状线距离,且测量误差在外科可接受范围内.MRI为临床手术选择及术前评估提供了有价值的影像学依据.

纺锤体成分25(SPC25)作为Ndc80复合体成员之一,是有丝分裂的重要调节因子,在染色体的分离过程中起着重要作用,同时也是纺锤体组装检查点所必须的,可维持遗传物质精确分配.SPC25异常表达会造成有丝分裂紊乱,导致细胞异常增殖,最终增加恶性肿瘤形成的几率.目前在多种恶性肿瘤中均发现SPC25过表达,研究SPC25在恶性肿瘤中的表达情况与患者预后及各项临床病理参数的相关性,探索SPC25在恶性肿瘤中的发生发展机制,寻求SPC25靶向治疗药物,充分发掘SPC25的应用价值,是为肿瘤患者寻得生机的重要途径.本文就SPC25在细胞分裂中的作用、SPC25在肝癌、肺癌、乳腺癌、前列腺癌和其他肿瘤中的研究及其在非肿瘤性病变中的研究作一综述.

Phosphoribosyl pyrophosphate synthetase 1 (PRPS1) is the first enzyme in the de novo purine nucleotide synthesis pathway and is essential for cell development. However, the effect of PRPS1 on melanoma proliferation and metastasis remains unclear. This study aimed to investigate the regulatory mechanism of PRPS1 in the malignant progression of melanoma. Here, we found PRPS1 was upregulated in melanoma and melanoma cells. In addition, our data indicated that PRPS1 could promote the proliferation and migration and invasion of melanoma both in vitro and in vivo. PRPS1 also could inhibit melanoma cell apoptosis. Furthermore, we found NRF2 is an upstream transcription factor of PRPS1 that drive malignant progression of melanoma.

Clear cell renal carcinoma (ccRCC) is histologically defined by its cytoplasmic lipid deposits. Lipid metabolism disorder largely increases the risk of ccRCC. In this study, we aimed to investigate the biological functions and molecular mechanisms of carnitine palmitoyl transferase 1A (CPT1A) in ccRCC. Our results showed that CPT1A is decreased in ccRCC clinical samples and cell lines compared with that in normal samples. Lentivirus overexpressing CPT1A was used to investigate the neoplastic phenotypes of ccRCC, and the results showed that lipid accumulation and tumor growth are attenuated both and . In addition, CPT1A prevents cholesterol uptake and lipid accumulation by increasing the peroxisome proliferator-activated receptor α (PPARα) level through regulation of Class B scavenger receptor type 1 (SRB1) and cluster of differentiation 36 (CD36). Furthermore, PI3K/Akt signaling pathway promotes tumor cell proliferation in ccRCC, which is related to the enhanced expression of CD36. Functionally, weakened CPT1A expression is critical for lipid accumulation to promote ccRCC development. Collectively, our research unveiled a novel function of CPT1A in lipid metabolism via PPARα/CD36 axis, which provides a new theoretical explanation for the pathogenesis of ccRCC. Targeting CPT1A may be a potential therapeutic strategy to treat ccRCC.

Background: Clear cell renal cell carcinoma (ccRCC) is a cell metabolic disease with high metastasis rate and poor prognosis. Our previous studies demonstrate that glucose-6-phosphate dehydrogenase (G6PD), the first and rate-limiting enzyme of the pentose phosphate pathway, is highly expressed in ccRCC and predicts poor outcomes of ccRCC patients. The aims of this study were to confirm the oncogenic role of G6PD in ccRCC and unravels novel mechanisms involving Cyclin E1 and MMP9 in G6PD-mediated ccRCC progression. Methods: Real-time RT-PCR, Western blot and immunohistochemistry were used to determine the expression patterns of G6PD, Cyclin E1 and MMP9 in ccRCC. TCGA dataset mining was used to identify Cyclin E1 and MMP9 correlations with G6PD expression, relationships between clinicopathological characteristics of ccRCC and the genes of interest, as well as the prognosis of ccRCC patients. The role of G6PD in ccRCC progression and the regulatory effect of G6PD on Cyclin E1 and MMP9 expression were investigated by using a series of cytological function assays in vitro. To verify this mechanism in vivo, xenografted mice models were established. Results: G6PD, Cyclin E1 and MMP9 were overexpressed and positively correlated in ccRCC, and they were associated with poor prognosis of ccRCC patients. Moreover, G6PD changed cell cycle dynamics, facilitated cells proliferation, promoted migration in vitro, and enhanced ccRCC development in vivo, more likely through enhancing Cyclin E1 and MMP9 expression. Conclusion: These findings present G6PD, Cyclin E1 and MMP9, which contribute to ccRCC progression, as novel biomarkers and potential therapeutic targets for ccRCC treatment.

正>原发性心包恶性肿瘤较为少见,以心包恶性间皮瘤居多,原发性心包脂肪肉瘤极为罕见,目前国内外报道甚少[1-2],而继发性心脏恶性病变的患病率是原发性心脏恶性肿瘤的20～40倍。为进一步提高对原发性心包恶性肿瘤的认识,避免临床漏诊及误诊,现结合相关文献,就1例转移性心包黏液样脂肪肉瘤（myxoid liposarcoma,MLPS）的临床病理学特征、鉴别诊断及相关预后予以报道。

文章首先阐述了5G时代新媒体的相关内容,然后分析了5G时代新媒体在研究生组织与网络协同育人中应用的"危"与"机",最后提出了5G时代新媒体在研究生组织与网络协同育人中应用的路径.

目的 通过为1例直肠癌同时性肝转移患者制定个性化综合治疗方案,探讨多学科团队(MDT)在直肠癌肝转移(CRLM)患者诊治中的作用.方法 2015年3月20日就诊于普外科的1例CRLM患者男性,54岁,在MDT(肝胆外科,胃肠外科,肿瘤科,放射科,影像科,病理科)病例讨论模式下对患者治疗全程不同时期进行全面评估和制定治疗方案.结果 经过MDT多次病例讨论及转化治疗后,患者直肠原发病灶及肝转移灶和复发灶接受两次手术及放化疗、靶向、局部射频等综合治疗,迄至2019年4月患者最终达到无瘤生存状态,实现生存获益.结论 MDT诊疗模式在直肠癌肝转移治疗中可提供个体化最佳方案,确保患者获得最佳治疗.