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Comprehensive Multi-Omics Analysis Reveals NPC2 and ITGAV Genes as Potential Prognostic Biomarkers in Gastrointestinal Cancers 综合多组学分析揭示NPC2和ITGAV基因是胃肠道癌症潜在的预后生物标志物
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-12-17 DOI: 10.1002/cnr2.70087
Moein Piroozkhah, Mohammadreza Zabihi, Pooya Jalali, Zahra Salehi

Background

Gastrointestinal cancers (GICs) continue to dominate in terms of both incidence and mortality worldwide. Due to the absence of efficient and accurate prognostic biomarkers, the prognosis and treatment outcomes of many GICs are poor. Identifying biomarkers to predict individual clinical outcomes efficiently is a fundamental challenge in clinical oncology. Although several biomarkers have been continually discovered, their predictive accuracy is relatively modest, and their therapeutic use is restricted. In light of this, the discovery of reliable biomarkers for predicting prognosis and outcome in GIC is urgently required.

Materials and Methods

We evaluated the Human Protein Atlas dataset and identified NPC Intracellular Cholesterol Transporter 2 (NPC2) and Integrin Subunit Alpha V (ITGAV) as probable poor predictive genes for these cancers. In addition, we used the GEPIA2, cBioPortal, UALCAN, LinkedOmics, STRING, Enrichr, TISDB, TIMER2.0, hTFTarget, miRTarBase, circBank, and drug–gene interaction database databases to conduct a comprehensive and systematic analysis of the NPC2 and ITGAV genes.

Result

Our results found high expression levels of NPC2 and ITGAV in most GICs. The aforementioned gene expressions were linked to several clinicopathological characteristics of GICs as well as poorer prognosis in LIHC and STAD. The most common alteration type of NPC2 was amplification, and for ITGAV was deep deletion. Significant promotor hypermethylation was also seen in NPC2 and ITGAV in PAAD and COAD, respectively. For the immunologic significance, NPC2 and ITGAV were positively correlated with the abundance of tumor-infiltrating lymphocytes and macrophages. Furthermore, various immunomodulators showed strong correlations with the expression of these genes. There were currently 10 small molecule drugs targeting ITGAV.

Conclusion

Consequently, our bioinformatics analysis showed that NPC2 and ITGAV might be used as potential biomarkers to determine the prognosis of various GICs and are also related to immune infiltration.

背景:胃肠道癌症(gic)在世界范围内的发病率和死亡率方面继续占主导地位。由于缺乏有效和准确的预后生物标志物,许多gic的预后和治疗结果都很差。识别生物标志物以有效预测个体临床结果是临床肿瘤学的一个基本挑战。尽管一些生物标记物不断被发现,但它们的预测准确性相对较低,而且它们的治疗用途也受到限制。鉴于此,迫切需要发现可靠的生物标志物来预测GIC的预后和结局。材料和方法:我们评估了人类蛋白质图集数据集,并确定鼻咽癌细胞内胆固醇转运蛋白2 (NPC2)和整合素亚单位α V (ITGAV)可能是这些癌症的不良预测基因。此外,我们利用GEPIA2、cbiopportal、UALCAN、LinkedOmics、STRING、富集、TISDB、TIMER2.0、hTFTarget、miRTarBase、circBank、药物-基因相互作用数据库等数据库对NPC2和ITGAV基因进行了全面系统的分析。结果:NPC2和ITGAV在大多数GICs中高表达。上述基因表达与GICs的几个临床病理特征以及LIHC和STAD的较差预后有关。NPC2基因最常见的变异类型是扩增,而ITGAV基因最常见的变异类型是深度缺失。在PAAD和COAD的NPC2和ITGAV中也分别观察到显著的启动子超甲基化。在免疫学意义上,NPC2和ITGAV与肿瘤浸润淋巴细胞和巨噬细胞丰度呈正相关。此外,各种免疫调节剂与这些基因的表达有很强的相关性。目前针对ITGAV的小分子药物有10种。结论:因此,我们的生物信息学分析表明,NPC2和ITGAV可能作为判断各种gic预后的潜在生物标志物,并与免疫浸润有关。
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引用次数: 0
Knockdown of Methylation-Related Gene MBD2 Blocks Cell Growth by Upregulating p21 Expression in Head and Neck Squamous Cell Carcinoma 敲除甲基化相关基因 MBD2 可通过上调 p21 表达阻止头颈部鳞状细胞癌细胞生长
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-12-16 DOI: 10.1002/cnr2.70080
Ting Cao, Xia Shen, Fei Pei, Taogeng Jiang, Jun Zhang, Hong Zhou

Background

Methyl-CpG-binding domain 2 (MBD2) attaches to methylated DNA, which mediates methylated gene transcription, leading to gene silencing and affecting tumor progression. The molecular mechanisms of MBD2 in head and neck squamous cell carcinoma (HNSCC) remain insufficiently characterized.

Aims

This study sought to assess the clinical relevance of MBD2 expression in HNSCC, with a particular focus on elucidating its functional role in tumor progression and its regulatory influence on p21 expression and cellular proliferation.

Methods

We analyzed the relationships between MBD2 expression, clinicopathological features, and survival outcomes in HNSCC patients using data from the UALCAN, TCGA, and cBioPortal databases. The functional role of MBD2 in HNSCC was further investigated through in vitro experiments. p21 expression was assessed using western blotting and qRT-PCR in TU212 and AMC-HN8 cells. These cells were treated with either shRNA targeting MBD2, 5-azacytidine (5-Aza), or a combination of shRNA MBD2 and 5-Aza. Additionally, cell proliferation and viability were measured in each treatment group.

Results

MBD2 was found to be frequently overexpressed in HNSCC tissues, and its altered expression was significantly associated with reduced overall survival (OS) and disease-free survival (DFS). Both shRNA-mediated MBD2 knockdown and 5-Aza treatment increased p21 expression in HNSCC cells, exhibiting similar functions with additive effects. Furthermore, both treatments significantly inhibited cell proliferation and viability.

Conclusion

These results indicated that shRNA-mediated MBD2 knockdown suppresses HNSCC cell growth by upregulating p21 expression. In addition to its role as an oncogene, MBD2 may serve as a prognostic biomarker and therapeutic target for HNSCC patients.

背景:甲基cpg结合域2 (methyll - cpg binding domain 2, MBD2)附着在甲基化DNA上,介导甲基化基因转录,导致基因沉默,影响肿瘤进展。MBD2在头颈部鳞状细胞癌(HNSCC)中的分子机制尚不清楚。目的:本研究旨在评估MBD2在HNSCC中表达的临床相关性,特别关注阐明其在肿瘤进展中的功能作用及其对p21表达和细胞增殖的调节作用。方法:我们使用来自UALCAN、TCGA和cBioPortal数据库的数据,分析了HNSCC患者MBD2表达、临床病理特征和生存结局之间的关系。通过体外实验进一步探讨MBD2在HNSCC中的功能作用。采用western blotting和qRT-PCR检测TU212和AMC-HN8细胞中p21的表达。这些细胞分别用靶向MBD2、5-氮杂胞苷(5-Aza)的shRNA或靶向MBD2和5-Aza的shRNA处理。并测定各处理组细胞增殖和活力。结果:MBD2在HNSCC组织中经常过表达,其表达改变与总生存期(OS)和无病生存期(DFS)降低显著相关。shrna介导的MBD2敲低和5-Aza处理均增加了HNSCC细胞中p21的表达,表现出相似的功能和叠加效应。此外,两种处理均显著抑制细胞增殖和活力。结论:shrna介导的MBD2下调可通过上调p21的表达抑制HNSCC细胞的生长。除了作为癌基因的作用外,MBD2还可以作为HNSCC患者的预后生物标志物和治疗靶点。
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引用次数: 0
Demographic and Treatment Analysis of Periosteal Osteosarcoma 骨膜骨肉瘤的人口统计学和治疗分析
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-12-15 DOI: 10.1002/cnr2.70086
Michael C. Larkins

Background and Aims

Periosteal osteosarcoma (PO) is a rare bone cancer that makes up between 1% and 6% of osteosarcomas. No epidemiological survey of the United States has been conducted to study this disease, and most of the literature is limited to single-center analyses and case reports. We seek to perform the first such assessment.

Methods

The Surveillance, Epidemiology, and End Results (SEER) Program was queried for patients with primary PO (ICD-O-3 code 9193/3). Analysis of demographic, disease, and treatment variables was conducted via Fisher's exact test and 20-year cause-specific survival (20y CSS) was assessed via logrank analysis.

Results

Fifty-four patients with PO were identified; median age was 20–24 years at diagnosis. Multivariate analysis demonstrated surgery provided 20y CSS benefit (hazard ratio [HR] = 0.08, p = 0.040) while chemotherapy (CTX) did not (p = 0.29); however, given the limited number of events (n = 11), recalculation of Cox regression for each variable demonstrated significance only with race (p = 0.026). Younger patients were more likely to be diagnosed with PO of the appendicular skeleton compared to the axial skeleton (p = 0.038). Mean survival time was greater among patients diagnosed with appendicular PO (16.0 years [14.2, 17.9]) compared to axial PO (10.9 years [9.5, 12.4]). Stage-stratified survival analysis demonstrated surgery alone was non-inferior to surgery with the addition of CTX (local disease: p = 0.37; regional disease: p = 0.85).

Conclusion

Axial PO is associated with decreased mean 20y CSS compared to appendicular PO, though in general, appendicular PO is more common than axial PO. In keeping with current literature, treatment of PO with CTX in addition to surgery should be reserved for high-risk patients, though its use in the treatment of PO is questionable.

背景和目的:骨膜骨肉瘤(PO)是一种罕见的骨癌,占骨肉瘤的 1%-6%。美国尚未对这种疾病进行流行病学调查,大多数文献仅限于单中心分析和病例报告。我们试图进行首次此类评估:方法:我们向监测、流行病学和最终结果(SEER)计划查询了原发性 PO(ICD-O-3 编码 9193/3)患者的情况。通过费雪精确检验对人口统计学、疾病和治疗变量进行了分析,并通过对数秩分析评估了20年病因特异性生存率(20年CSS):结果:共发现 54 名 PO 患者;诊断时的中位年龄为 20-24 岁。多变量分析表明,手术可使患者获得20年CSS生存率(危险比[HR] = 0.08,p = 0.040),而化疗(CTX)则没有(p = 0.29);然而,由于事件数量有限(n = 11),对每个变量重新进行Cox回归计算后发现,只有种族因素具有显著性(p = 0.026)。与轴向骨骼相比,更年轻的患者更有可能被诊断为阑尾骨骼 PO(p = 0.038)。被确诊为阑尾PO的患者的平均生存时间(16.0年 [14.2,17.9])比被确诊为轴向PO的患者(10.9年 [9.5,12.4])长。分期生存分析表明,单纯手术治疗效果不优于加用CTX的手术治疗(局部疾病:P = 0.37;区域性疾病:P = 0.85):结论:与阑尾PO相比,轴向PO与平均20年CSS下降有关,但总体而言,阑尾PO比轴向PO更常见。根据目前的文献,高危患者应在手术的基础上使用 CTX 治疗 PO,但 CTX 在 PO 治疗中的应用尚存疑问。
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引用次数: 0
Exploring Oesophageal Cancer in Ethiopia: Elevated Incidence in Females and Younger Cases 探讨埃塞俄比亚食管癌:女性和年轻病例的发病率升高。
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-12-12 DOI: 10.1002/cnr2.70048
Girma Mulisa, Tamrat Abebe, Bekele Gutema, Jannatul Mahmuda, Md. Al Amin Khan, Tarik Gheit, Zdenko Herceg, Fazlur Rahman Talukdar

Background

Oesophageal cancer is a public health concern in Ethiopia. Identifying the incidence and demographic profile of the two histological subtypes: oesophageal squamous cell carcinoma (ESCC) and oesophageal adenocarcinoma (EAC) are the key steps in recognizing the disease burden and potential aetiopathological associations.

Aim

The aim of this study is to identify the age and gender-specific incidence patterns of the most common subtype of oesophageal cancer in a high-incidence area of Ethiopia.

Methods

A retrospective cross-sectional study from a high-incidence oesophageal cancer district in Ethiopia identified 630 cases from the pathology registry of nine hospitals. The patient records were carefully reviewed and data on age, gender, tumour location and histological types was systematically compiled. The patient data were retrieved and descriptive statistics were used to generate results.

Results

ESCC subtype, accounted for constituting 500 (79.437%) cases. A gender disparity was observed, with 62.80% of cases occurring in females and 37.20% in males. This distribution of higher female ESCC incidences aligns with previous findings indicating a regional consistency and probable aetiological factor. Furthermore, ESCC incidence peaked at 40–50 years in females, highlighting an age-related incidence trend. EAC was observed in 67 (51.5%) females and 63 (48.5%) males showing similar prevalence. Spatial analysis revealed that the majority of ESCC cases were located in the lower oesophagus, followed by the middle part, with fewer instances in the upper oesophagus.

Conclusion

This study from Ethiopia identified ESCC as the predominant subtype, with a marked female predominance and age-related gender disparities. EAC with a lesser proportion identified with consistent spatial distribution patterns in both genders provide valuable insights into the epidemiological landscape of this disease. These findings emphasize the urgency of targeted research to uncover the underlying factors.

背景:食管癌是埃塞俄比亚的一个公共卫生问题。确定两种组织学亚型:食管鳞状细胞癌(ESCC)和食管腺癌(EAC)的发病率和人口统计学特征是认识疾病负担和潜在病因病理学关联的关键步骤。目的:本研究的目的是确定埃塞俄比亚高发地区最常见的食管癌亚型的年龄和性别特异性发病率模式。方法:一项来自埃塞俄比亚食管癌高发地区的回顾性横断面研究,从9家医院的病理登记处确定了630例病例。我们仔细审查了患者的记录,并系统地汇编了年龄、性别、肿瘤位置和组织学类型的数据。检索患者数据并使用描述性统计来生成结果。结果:ESCC亚型占500例(79.437%)。性别差异较大,女性占62.80%,男性占37.20%。女性ESCC发病率较高的分布与先前的研究结果一致,表明存在区域一致性和可能的病因因素。此外,ESCC发病率在40-50岁的女性中达到高峰,突出了与年龄相关的发病率趋势。女性67例(51.5%),男性63例(48.5%),发病率相近。空间分析显示,ESCC以食管下段居多,其次为中段,上段较少。结论:来自埃塞俄比亚的这项研究确定ESCC为主要亚型,具有明显的女性优势和与年龄相关的性别差异。较小比例的EAC在两性中具有一致的空间分布模式,这为了解该病的流行病学格局提供了有价值的见解。这些发现强调了有针对性的研究以揭示潜在因素的紧迫性。
{"title":"Exploring Oesophageal Cancer in Ethiopia: Elevated Incidence in Females and Younger Cases","authors":"Girma Mulisa,&nbsp;Tamrat Abebe,&nbsp;Bekele Gutema,&nbsp;Jannatul Mahmuda,&nbsp;Md. Al Amin Khan,&nbsp;Tarik Gheit,&nbsp;Zdenko Herceg,&nbsp;Fazlur Rahman Talukdar","doi":"10.1002/cnr2.70048","DOIUrl":"10.1002/cnr2.70048","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Oesophageal cancer is a public health concern in Ethiopia. Identifying the incidence and demographic profile of the two histological subtypes: oesophageal squamous cell carcinoma (ESCC) and oesophageal adenocarcinoma (EAC) are the key steps in recognizing the disease burden and potential aetiopathological associations.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aim</h3>\u0000 \u0000 <p>The aim of this study is to identify the age and gender-specific incidence patterns of the most common subtype of oesophageal cancer in a high-incidence area of Ethiopia.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A retrospective cross-sectional study from a high-incidence oesophageal cancer district in Ethiopia identified 630 cases from the pathology registry of nine hospitals. The patient records were carefully reviewed and data on age, gender, tumour location and histological types was systematically compiled. The patient data were retrieved and descriptive statistics were used to generate results.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>ESCC subtype, accounted for constituting 500 (79.437%) cases. A gender disparity was observed, with 62.80% of cases occurring in females and 37.20% in males. This distribution of higher female ESCC incidences aligns with previous findings indicating a regional consistency and probable aetiological factor. Furthermore, ESCC incidence peaked at 40–50 years in females, highlighting an age-related incidence trend. EAC was observed in 67 (51.5%) females and 63 (48.5%) males showing similar prevalence. Spatial analysis revealed that the majority of ESCC cases were located in the lower oesophagus, followed by the middle part, with fewer instances in the upper oesophagus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>This study from Ethiopia identified ESCC as the predominant subtype, with a marked female predominance and age-related gender disparities. EAC with a lesser proportion identified with consistent spatial distribution patterns in both genders provide valuable insights into the epidemiological landscape of this disease. These findings emphasize the urgency of targeted research to uncover the underlying factors.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"7 12","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11635477/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812112","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gastric Outlet Obstruction as a First Symptom of a Non-Muscle Invasive Bladder Cancer (NMIBC) Progression—A Case Report 胃出口梗阻作为非肌性浸润性膀胱癌(NMIBC)进展的第一症状- 1例报告。
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-12-12 DOI: 10.1002/cnr2.70077
Duje Apostolski, Florian Roitner

Background

Metastatic disease of a urinary bladder cancer localized in the upper abdomen is very rare. This case report describes the first patient with a urinary bladder cancer progression, initially presenting as a gastric outlet obstruction due to peritoneal carcinomatosis.

Case

We present the case of a 78-years-old male patient who was admitted to Hospital St. Josef Braunau in Austria with persistent vomiting. In the medical history, the most prominent finding was a diagnosed high-risk NMIBC. At the time, patient was between 2. and 3. BCG maintenance instillation cycle, following two transurethral resections. Routine follow-up cystoscopy 1 month before admission to our department showed no evidence of disease recurrence. Due to the therapy resistant vomiting, gastroscopy was performed, revealing duodenal stenosis without mucosal changes. Subsequently performed abdominal CT-scan showed homogenous swelling of the mesenteric fat tissue around duodenum, spreading retroperitoneal to both kidneys. In the absence of the typical peritoneal carcinomatosis features, the finding was firstly described as an inflammation of mesenteric fat or panniculitis mesenterialis. Further deterioration of patient's condition and later occurred bilateral hydronephrosis raised a suspicion of peritoneal carcinomatosis. Consequently, conducted laparoscopic exploration confirmed the suspicion describing the tissue conglomerate typical for peritoneal carcinomatosis surrounding the duodenum. Pathohistological analysis of taken samples proved urothelial cancer cells, confirming the diagnosis of metastatic bladder cancer disease.

Conclusion

This case report presents a very unusual presentation of metastatic urinary bladder cancer that could help clinicians to consider this diagnosis when encountering similar clinical features.

背景:膀胱癌转移到上腹部是非常罕见的。本病例报告描述了第一例膀胱癌进展的患者,最初表现为腹膜癌病引起的胃出口梗阻。病例:我们提出的情况下,78岁的男性患者住进医院圣约瑟夫布劳瑙在奥地利持续呕吐。在病史中,最突出的发现是诊断为高风险的NMIBC。当时,病人年龄在2岁之间。和3。卡介苗维持灌注周期,在两次经尿道切除后。入院前1个月例行膀胱镜随访未见疾病复发。由于治疗抵抗性呕吐,胃镜检查显示十二指肠狭窄,未见粘膜改变。随后进行腹部ct扫描显示十二指肠周围肠系膜脂肪组织均匀肿胀,向腹膜后扩散至双肾。在没有典型腹膜癌特征的情况下,该发现首先被描述为肠系膜脂肪炎症或肠系膜炎。患者病情进一步恶化,后来出现双侧肾积水,怀疑为腹膜癌。因此,腹腔镜探查证实了对十二指肠周围腹膜癌典型组织团块的怀疑。病理组织学分析证实尿路上皮癌细胞,确认转移性膀胱癌的诊断。结论:本病例报告提出了一个非常不寻常的转移性膀胱癌的表现,可以帮助临床医生在遇到类似的临床特征时考虑这种诊断。
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引用次数: 0
An Integrated Approach to Develop a Potent Vaccine Candidate Construct Against Prostate Cancer by Utilizing Machine Learning and Bioinformatics 利用机器学习和生物信息学开发一种有效的前列腺癌候选疫苗的综合方法。
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-12-09 DOI: 10.1002/cnr2.70079
Aqel Albutti

Background

Prostate cancer is the most common malignancy among males. Prostaglandin G/H synthase (PGHS) is an essential enzyme in the synthesis of prostaglandins, and its activation has been linked to many malignancies, including colorectal cancer.

Aims

Due to the limited effectiveness and specificity of existing prostate cancer therapies, this study was designed to formulate improved treatment techniques.

Methods

Several immunoinformatic, reverse vaccinology, and molecular modeling methodologies were used to discover B- and T-cell epitopes for the glioblastoma multiforme tumor PGH2_HUMAN. This research evaluated Prostaglandin G/H synthase 2 protein as a potential vaccine candidate against the malignancy. The multi-epitope vaccine architecture is engineered to activate the immune system, with each epitope docked to its respective HLAs. Further, MD simulations analysis was performed to validate the findings.

Results

A multi-epitope subunit vaccine candidate was developed by concatenating the chosen B- and T-cell epitopes. Results yield a codon adaptive index (CAI) of 0.93 and a GC content of 56.77%. Thus, it conforms to a biological requirement for effective protein expression, suggesting competent vaccine efficacy inside the Escherichia coli system. Significant interleukin and cytokine responses were seen, characterized by elevated levels of IL-2 and IFN-γ in the immune system's response to the immunization. Molecular docking demonstrated an efficient binding affinity of −278 kcal/mol, with hydrogen bonding to several residues. Furthermore, the system total root mean square deviation (RMSD) reached 3.23 Å, with a maximum of up to 5.0 Å at the 100 ns time point but remains stable till 400 ns time intervals followed by stable root mean square fluctuation (RMSF) and radius of gyration values. The hydrogen bond cloud residues are the critical sites that significantly influence the binding energies of MMPBSA and MMGBSA via substantial van der Waals interactions.

Conclusion

It has been determined that these in silico analyses will further augment the comprehension necessary for advancing the creation of targeted therapies for chemotherapeutic cancer treatments.

背景:前列腺癌是男性最常见的恶性肿瘤。前列腺素G/H合成酶(PGHS)是合成前列腺素的必需酶,其激活与包括结直肠癌在内的许多恶性肿瘤有关。目的:由于现有前列腺癌治疗方法的有效性和特异性有限,本研究旨在制定改进的治疗技术。方法:采用多种免疫信息学、反向疫苗学和分子建模方法,发现多形性胶质母细胞瘤PGH2_HUMAN的B细胞和t细胞表位。本研究评价前列腺素G/H合成酶2蛋白作为抗恶性肿瘤的潜在候选疫苗。多表位疫苗结构被设计为激活免疫系统,每个表位与各自的hla对接。此外,进行了MD模拟分析来验证研究结果。结果:通过连接选定的B细胞和t细胞表位,获得了一种多表位亚单位候选疫苗。结果表明,该菌株的密码子自适应指数(CAI)为0.93,GC含量为56.77%。因此,它符合有效蛋白表达的生物学要求,表明疫苗在大肠杆菌系统内具有有效的效力。显著的白细胞介素和细胞因子反应被观察到,其特征是免疫系统对免疫反应中IL-2和IFN-γ水平升高。分子对接显示出-278 kcal/mol的有效结合亲和力,并与多个残基形成氢键。此外,系统总均方根偏差(RMSD)达到3.23 Å,在100 ns时间点最大可达5.0 Å,但在400 ns时间间隔内保持稳定,随后均方根波动(RMSF)和旋转半径值稳定。氢键云残基是通过大量的范德华相互作用显著影响MMPBSA和MMGBSA结合能的关键位点。结论:已经确定,这些计算机分析将进一步增强对推进化疗性癌症治疗的靶向治疗创造所必需的理解。
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引用次数: 0
Investigation of the Effects of Blocking Potassium Channels With 4-Aminopyridine on Paclitaxel Activity in Breast Cancer Cell Lines 4-氨基吡啶阻断钾通道对乳腺癌细胞紫杉醇活性影响的研究。
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-12-08 DOI: 10.1002/cnr2.70072
Esra M. Cüce-Aydoğmuş, G. Ayşe İnhan-Garip

Background

Paclitaxel (PTX) has been used as a chemotherapeutic agent for several malignancies, including breast cancer, and efforts to increase the efficiency of PTX are continuous. Previous studies have shown that the voltage-gated K+ channels are over-expressed in breast cancer cell lines; therefore, blocking this type of K+ channel reduces cell proliferation and viability.

Aims

In this study, FDA-approved 4-aminopyridine (4-AP), a voltage-gated potassium channel blocker, was used in combination with PTX to improve the anticancer activity of PTX in MCF-7 and MDA-MB-231 cell lines.

Methods and Results

Viability was determined with trypan blue, a clonogenic assay was performed, and the cell cycle was determined with a flow cytometer and immunochemistry. To gain an insight into the mechanism, intracellular K+ concentration, intracellular Ca2+ (calcium) concentration, and transmembrane potential measurements were made with corresponding fluorescent dyes. The apoptotic cell number was determined using Annexin /PI method by flow cytometer. Viability decreased with combination therapy and the clonogenic assay proved decreased colony formation. The apoptotic cell number was increased after treatment with the combination in both cell lines. Cell cycle measurements showed G1 arrest for both MCF-7 and MDA-MB-231 cell lines upon 4-AP treatment. PTX caused G1 arrest in MCF-7 cells and S phase arrest in MDA-MB-231 cells. Combination treatment caused S phase arrest in MCF-7 cells and S phase and G2/M phase arrest in MDA-MB-231 cells. Intracellular K+ concentration was increased after all treatments in both cell lines. Ca2+ concentration was increased significantly after combination treatment. Depolarization in the transmembrane potential was observed after all treatments in both cell lines.

Conclusion

Biophysical parameters like the transmembrane potential and ion fluxes have been defined in cancer progression which can provide new aspects for cancer treatments. This study shows that the combination of 4-AP with PTX is a promising alternative the mechanism of which needs further investigation considering the results obtained for Ca2+, K+, and membrane potential.

背景:紫杉醇(PTX)已被用作多种恶性肿瘤的化疗药物,包括乳腺癌,并且不断努力提高PTX的效率。先前的研究表明,电压门控K+通道在乳腺癌细胞系中过度表达;因此,阻断这种类型的K+通道会降低细胞的增殖和活力。目的:在本研究中,fda批准的电压门控钾通道阻滞剂4-氨基吡啶(4-AP)与PTX联合使用,以提高PTX在MCF-7和MDA-MB-231细胞系中的抗癌活性。方法和结果:台盼蓝法测定细胞活力,克隆生成法测定细胞周期,流式细胞仪和免疫化学法测定细胞周期。为了深入了解其机制,用相应的荧光染料测量细胞内K+浓度、细胞内Ca2+(钙)浓度和跨膜电位。流式细胞仪Annexin /PI法测定凋亡细胞数。联合治疗后细胞活力下降,克隆生成试验证实菌落形成减少。两种细胞系联合用药后凋亡细胞数均增加。细胞周期测量显示,4-AP处理后MCF-7和MDA-MB-231细胞系的G1停滞。PTX在MCF-7细胞中引起G1期阻滞,在MDA-MB-231细胞中引起S期阻滞。联合处理导致MCF-7细胞S期阻滞,MDA-MB-231细胞S期和G2/M期阻滞。两种细胞系在所有处理后细胞内K+浓度均升高。联合治疗后Ca2+浓度显著升高。两种细胞系在所有处理后均观察到跨膜电位的去极化。结论:明确了肿瘤进展过程中的跨膜电位、离子通量等生物物理参数,为肿瘤治疗提供了新的思路。本研究表明,4-AP与PTX联合是一种很有前景的替代方案,考虑到Ca2+, K+和膜电位的结果,其机制有待进一步研究。
{"title":"Investigation of the Effects of Blocking Potassium Channels With 4-Aminopyridine on Paclitaxel Activity in Breast Cancer Cell Lines","authors":"Esra M. Cüce-Aydoğmuş,&nbsp;G. Ayşe İnhan-Garip","doi":"10.1002/cnr2.70072","DOIUrl":"10.1002/cnr2.70072","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Paclitaxel (PTX) has been used as a chemotherapeutic agent for several malignancies, including breast cancer, and efforts to increase the efficiency of PTX are continuous. Previous studies have shown that the voltage-gated K<sup>+</sup> channels are over-expressed in breast cancer cell lines; therefore, blocking this type of K<sup>+</sup> channel reduces cell proliferation and viability.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>In this study, FDA-approved 4-aminopyridine (4-AP), a voltage-gated potassium channel blocker, was used in combination with PTX to improve the anticancer activity of PTX in MCF-7 and MDA-MB-231 cell lines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>Viability was determined with trypan blue, a clonogenic assay was performed, and the cell cycle was determined with a flow cytometer and immunochemistry. To gain an insight into the mechanism, intracellular K<sup>+</sup> concentration, intracellular Ca<sup>2+</sup> (calcium) concentration, and transmembrane potential measurements were made with corresponding fluorescent dyes. The apoptotic cell number was determined using Annexin /PI method by flow cytometer. Viability decreased with combination therapy and the clonogenic assay proved decreased colony formation. The apoptotic cell number was increased after treatment with the combination in both cell lines. Cell cycle measurements showed G<sub>1</sub> arrest for both MCF-7 and MDA-MB-231 cell lines upon 4-AP treatment. PTX caused G<sub>1</sub> arrest in MCF-7 cells and S phase arrest in MDA-MB-231 cells. Combination treatment caused S phase arrest in MCF-7 cells and S phase and G<sub>2</sub>/M phase arrest in MDA-MB-231 cells. Intracellular K<sup>+</sup> concentration was increased after all treatments in both cell lines. Ca<sup>2+</sup> concentration was increased significantly after combination treatment. Depolarization in the transmembrane potential was observed after all treatments in both cell lines.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Biophysical parameters like the transmembrane potential and ion fluxes have been defined in cancer progression which can provide new aspects for cancer treatments. This study shows that the combination of 4-AP with PTX is a promising alternative the mechanism of which needs further investigation considering the results obtained for Ca<sup>2+</sup>, K<sup>+</sup>, and membrane potential.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"7 12","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11625685/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142794400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
An Inflammation-Related lncRNA Signature for Prognostic Prediction in Colorectal Cancer 一个炎症相关的lncRNA标记用于结直肠癌的预后预测。
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-12-05 DOI: 10.1002/cnr2.70043
Zhenling Zhang, Yingshu Luo, Yuan Liu, Jiangnan Ren, Zhaoxiong Fang, Yanzhi Han

Background

Colorectal cancer (CRC) represents a commonly diagnosed malignancy affecting the digestive system. Mounting evidence shows long noncoding RNAs (lncRNAs) contribute to carcinogenesis. However, inflammation-related lncRNAs (IRLs) regulating CRC are poorly defined.

Aims

The current study aimed to develop an IRL signature for predicting prognosis in CRC and to examine the involved molecular mechanism.

Methods and Results

RNA-seq findings and patient data were retrieved from The Cancer Genome Atlas (TCGA), and inflammation-associated genes were obtained from the GeneCards database. IRLs with differential expression were determined with “limma” in R. Using correlation and univariable Cox analyses, prognostic IRLs were identified. The least absolute shrinkage and selection operator (LASSO) algorithm was employed to construct a prognostic model including 13 IRLs. The model's prognostic value was examined by Kaplan–Meier (K-M) survival curve and receiver operating characteristic (ROC) curve analyses. Furthermore, the association of the signature with the immune profile was assessed. Finally, RT-qPCR was carried out for verifying the expression of inflammation-related lncRNAs in nonmalignant and malignant tissue samples. A model containing 13 inflammation-related lncRNAs was built and utilized to classify cases into two risk groups based on risk score. The signature-derived risk score had a higher value in predicting survival compared with traditionally used clinicopathological properties in CRC cases. In addition, marked differences were detected in immune cells between the two groups, including CD4+ T cells and M2 macrophages. Furthermore, RT-qPCR confirmed the expression patterns of these 13 lncRNAs were comparable to those of the TCGA-CRC cohort.

Conclusion

The proposed 13-IRL signature is a promising biomarker and may help the clinical decision-making process and improve prognostic evaluation in CRC.

背景:结直肠癌(CRC)是一种常见的影响消化系统的恶性肿瘤。越来越多的证据表明,长链非编码rna (lncRNAs)参与致癌作用。然而,调节CRC的炎症相关lncrna (irl)定义不清。目的:本研究旨在建立预测结直肠癌预后的IRL信号,并探讨其分子机制。方法和结果:从癌症基因组图谱(TCGA)中检索RNA-seq结果和患者数据,从GeneCards数据库中获取炎症相关基因。差异表达的irl用“limma”在r中确定,使用相关性和单变量Cox分析,确定预后irl。采用最小绝对收缩和选择算子(LASSO)算法构建包含13个irl的预后模型。通过Kaplan-Meier (K-M)生存曲线和受试者工作特征(ROC)曲线分析检验模型的预后价值。此外,还评估了该特征与免疫特征的关联。最后,通过RT-qPCR验证炎症相关lncrna在非恶性和恶性组织样本中的表达。构建包含13个炎症相关lncrna的模型,并根据风险评分将病例分为两个风险组。在CRC病例中,与传统使用的临床病理特性相比,特征衍生风险评分在预测生存方面具有更高的价值。此外,两组免疫细胞CD4+ T细胞和M2巨噬细胞也有明显差异。此外,RT-qPCR证实了这13个lncrna的表达模式与TCGA-CRC队列的表达模式相似。结论:提出的13-IRL标记是一种有前景的生物标志物,可能有助于临床决策过程和改善CRC的预后评估。
{"title":"An Inflammation-Related lncRNA Signature for Prognostic Prediction in Colorectal Cancer","authors":"Zhenling Zhang,&nbsp;Yingshu Luo,&nbsp;Yuan Liu,&nbsp;Jiangnan Ren,&nbsp;Zhaoxiong Fang,&nbsp;Yanzhi Han","doi":"10.1002/cnr2.70043","DOIUrl":"10.1002/cnr2.70043","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Colorectal cancer (CRC) represents a commonly diagnosed malignancy affecting the digestive system. Mounting evidence shows long noncoding RNAs (lncRNAs) contribute to carcinogenesis. However, inflammation-related lncRNAs (IRLs) regulating CRC are poorly defined.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Aims</h3>\u0000 \u0000 <p>The current study aimed to develop an IRL signature for predicting prognosis in CRC and to examine the involved molecular mechanism.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods and Results</h3>\u0000 \u0000 <p>RNA-seq findings and patient data were retrieved from The Cancer Genome Atlas (TCGA), and inflammation-associated genes were obtained from the GeneCards database. IRLs with differential expression were determined with “limma” in R. Using correlation and univariable Cox analyses, prognostic IRLs were identified. The least absolute shrinkage and selection operator (LASSO) algorithm was employed to construct a prognostic model including 13 IRLs. The model's prognostic value was examined by Kaplan–Meier (K-M) survival curve and receiver operating characteristic (ROC) curve analyses. Furthermore, the association of the signature with the immune profile was assessed. Finally, RT-qPCR was carried out for verifying the expression of inflammation-related lncRNAs in nonmalignant and malignant tissue samples. A model containing 13 inflammation-related lncRNAs was built and utilized to classify cases into two risk groups based on risk score. The signature-derived risk score had a higher value in predicting survival compared with traditionally used clinicopathological properties in CRC cases. In addition, marked differences were detected in immune cells between the two groups, including CD4<sup>+</sup> T cells and M2 macrophages. Furthermore, RT-qPCR confirmed the expression patterns of these 13 lncRNAs were comparable to those of the TCGA-CRC cohort.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>The proposed 13-IRL signature is a promising biomarker and may help the clinical decision-making process and improve prognostic evaluation in CRC.</p>\u0000 </section>\u0000 </div>","PeriodicalId":9440,"journal":{"name":"Cancer reports","volume":"7 12","pages":""},"PeriodicalIF":1.5,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11621381/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142784244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Anti-Cancer Effect of Sulforaphane in Human Pancreatic Cancer Cells Mia PaCa-2 萝卜硫素对人胰腺癌细胞的抗癌作用
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-12-04 DOI: 10.1002/cnr2.70074
Min Ju Park, Yoon Hee Kim

Background

Pancreatic cancer is difficult to treat early as it has no early symptoms. The presence of sulforaphane (SFN) in cruciferous vegetables has been found to possess anti-cancer effects in gastric and colon cancers. Glycogen synthase kinase-3 beta (GSK-3β), a serine/threonine kinase, plays a significant role in pancreatic cancer progression, influencing tumor growth, metastasis, and treatment resistance. Targeting GSK-3β has shown potential to enhance the efficacy of chemotherapy. However, the mechanism underlying the anticancer effects of SFN on pancreatic cancer through GSK-3β is unclear.

Aims

In this study, we examined the anticancer effects of SFN in human pancreatic cancer cell line Mia PaCa-2 and evaluated its molecular mechanisms with respect to the GSK-3β-related pathway.

Methods and Results

SFN increased the protein expression of the phosphorylated form of GSK3β (Ser9). In the Wingless Int-1 homolog/β-catenin pathway, GSK3β induced apoptosis by phosphorylating β-catenin. However, in mutant Kirsten rat sarcoma viral oncogene homolog-like-dependent cells such as Mia PaCa-2, GSK3β was suppressed and the β-catenin level was increased, thus inducing apoptosis. Indeed, SFN increased the protein expression of β-catenin in the cytoplasm and nucleus. Subsequently, we measured the level of cMyc, the target gene of β-catenin. SFN decreased cMyc expression despite an increase in the β-catenin. We measured the expression of nuclear factor (NF)-κB, a downstream factor of GSK3β and an upstream factor of cMyc. SFN decreased the expression of NF-κB and cMyc, indicating that SFN inhibits cell proliferation by suppressing the GSK3β/NF-κB/cMyc pathway. As the suppression of NF-κB results in a decrease in B-cell lymphoma 2 (BCL-2) which is the anti-apoptotic gene, we tested the effect of SFN in the expression of BCL-2. SFN inhibited the expression of BCL-2 and increased the ratio of the apoptotic regulator gene BCL-2 associated X (BAX), where SFN induced the cleaved cysteine aspartase-3 and poly-adenosine diphosphate ribose polymerase.

Conclusion

These results indicate that SFN may have therapeutic potential in the inhibition of pancreatic cancer.

背景:胰腺癌没有早期症状,早期治疗困难。十字花科蔬菜中的萝卜硫素(SFN)已被发现对胃癌和结肠癌具有抗癌作用。糖原合成酶激酶-3β (GSK-3β)是一种丝氨酸/苏氨酸激酶,在胰腺癌的进展、肿瘤生长、转移和治疗抵抗中起重要作用。靶向GSK-3β已显示出提高化疗疗效的潜力。然而,SFN通过GSK-3β对胰腺癌产生抗癌作用的机制尚不清楚。目的:在本研究中,我们检测了SFN对人胰腺癌细胞系Mia PaCa-2的抗癌作用,并就gsk -3β相关途径评估其分子机制。方法和结果:SFN增加GSK3β (Ser9)磷酸化形式的蛋白表达。在Wingless Int-1同源物/β-catenin通路中,GSK3β通过磷酸化β-catenin诱导细胞凋亡。然而,在突变型Kirsten大鼠肉瘤病毒癌基因同源样依赖细胞Mia PaCa-2中,GSK3β被抑制,β-catenin水平升高,从而诱导细胞凋亡。确实,SFN增加了细胞质和细胞核中β-catenin的蛋白表达。随后,我们测量了β-连环蛋白靶基因cMyc的水平。SFN降低了cMyc的表达,尽管β-catenin增加。我们检测了GSK3β的下游因子核因子(NF)-κB和cMyc的上游因子的表达。SFN降低了NF-κB和cMyc的表达,表明SFN通过抑制GSK3β/NF-κB/cMyc通路抑制细胞增殖。由于抑制NF-κB导致抗凋亡基因b细胞淋巴瘤2 (BCL-2)的表达减少,我们检测了SFN对BCL-2表达的影响。SFN抑制BCL-2的表达,增加凋亡调节基因BCL-2相关X (BAX)的比例,其中SFN诱导裂解半胱氨酸天冬氨酸酶-3和多腺苷二磷酸核糖聚合酶。结论:SFN可能具有抑制胰腺癌的治疗潜力。
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引用次数: 0
Fathers' Experience of Their Child's Paediatric Brain Tumour 父亲对孩子患小儿脑瘤的经历
IF 1.5 Q4 ONCOLOGY Pub Date : 2024-12-03 DOI: 10.1002/cnr2.70061
Florence Labrell, Christine Hassler, Christelle Dufour, Jacques Grill, Hugo Câmara-Costa

Background

This exploratory study explores the impact of paediatric brain cancer on the experiences of the fathers from the time of diagnosis, while most studies have focused on the mothers.

Methods

The content of interviews conducted with six fathers of children who had brain tumours at the age of approximately 10 years was analysed using a qualitative methodology, following the COREQ guidelines.

Results

The fathers first talked about their feelings about the way the brain tumour affected their child and how he/she coped with the illness and treatments, and they also described the difficulties encountered. These French fathers likewise talked about their rights, their need to be listened to, and their wish to remain close to their child during treatment.

Conclusion

Improving communication with fathers during care and medical visits could help promote more balanced support for both parents in the vulnerable period of serious paediatric illnesses such as brain tumours.

本探索性研究旨在探讨儿童脑癌从诊断时起对父亲经历的影响,而大多数研究都集中在母亲身上。方法根据COREQ指南,采用定性方法对6名10岁左右患有脑肿瘤的儿童父亲的访谈内容进行分析。结果父亲们首先谈到了他们对脑肿瘤影响孩子的感受,以及他/她如何应对疾病和治疗,他们也描述了遇到的困难。这些法国父亲同样谈到了他们的权利,他们需要被倾听,以及他们希望在治疗期间与孩子保持密切联系。结论在儿童严重疾病如脑肿瘤的易危期,改善与父亲的沟通有助于促进对父母双方的平衡支持。
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引用次数: 0
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