Cancer Translational Medicine

Original Research | Open Access

Vol.8 (2022) | Issue-3 | Page No: 92-103

DOI: https://doi-ds.org/doilink/09.2022-42577891/A3

Quercetin Inhibits the Proliferation and Migration of Pancreatic Adenocarcinoma by Targeting the Prognostic-related Gene MMP1 via Bioinformatics and Network Pharmacology

Zhenhua Zu1,2#, Zhongguo Zhu3#, Zhiyu Xia2, Hongrang Chen1*, Yongsheng Li1*

Affiliations  

1. Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China

2. Department of Clinical Medicine, The First Clinical College of Anhui Medical University, Hefei, Anhui, China

3. Department of Rehabilitation Therapy, The First Clinical College of Anhui Medical University, Hefei, Anhui, China

# These authors contributed equally.

* Corresponding Author

Address for correspondence: Dr. Yongsheng Li, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No. 218, Jixi Road, Shushan District, Hefei 230022, Anhui, China. E-mail: ayfy_yshli @163.com

Dr. Hongrang Chen, Department of General Surgery, The First Affiliated Hospital of Anhui Medical University, No.218 Jixi Road, Shushan District, Hefei 230022, Anhui, China. E-mail: hongrangchen1988@163.com


Important Dates  

Date of Submission:   05-Jul-2022

Date of Acceptance:   12-Aug-2022

Date of Publication:   29-Sep-2022

ABSTRACT

Aim: To analyze the key prognostic genes and potential traditional Chinese medicine (TCM) targets of pancreatic adenocarcinoma (PAAD) through bioinformatics and TCM network pharmacology.

Methods: Differentially expressed genes (DEGs) in PAAD and adjacent noncancerous tissues were screened using GSE15471, GSE41368, and GSE62165 datasets from GEO Database. DEGs were subjected to GO and KEGG pathway enrichment analysis at the David website, the protein-protein interaction network (PPI) was drawn through the STRING database, and the Hub genes were obtained using Cytoscape software. Transcriptional expression and prognosis of Hub genes were analyzed in the GEPIA database. Four Chinese medicinal active ingredients and related targets were obtained from the Chinese Medicine System Pharmacology (TCMSP) database. A Venn diagram was used to screen the intersection targets of TCM and PAAD. PPI was constructed by Cytoscape. Finally, molecular docking verification was performed by AutoDock and PyMol.

Results: Total DEGs obtained were 151. GO and KEGG enrichment analyses indicated the involvement of Hub genes in affecting peptidase inhibitor activity, serine hydrolase and endopeptidase activity, glycosaminoglycan binding, Cell-Extracellular Matrix (ECM) receptor interaction, and ECM adhesion-related pathways. Quercetin and its core targets MMP2, IGFBP3, EGF, and MMP1 were obtained by network pharmacology analysis and PPI. Further molecular docking results showed that the ligand binding of the MMP1 protein receptor and the compound was stable and hydrogen bond interaction was formed.

Conclusion: Quercetin potentially inhibits the proliferation and migration of PAAD by targeting the MMP1 gene.

Keywords: Pancreatic adenocarcinoma, traditional Chinese medicine, network pharmacology, MMP1, prognosis


INTRODUCTION

Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies with the lowest survival rate worldwide.[1] Although the therapeutic approaches for pancreatic adenocarcinoma have been improved, the prognosis of patients remains poor, with a median survival of only 3-6 months and a 5-year survival rate of < 5%.[2] At present, surgical resection is the only curative therapy for pancreatic adenocarcinoma, but at diagnosis, it is often advanced and cannot undergo radical surgery, the reasons for which are attributed to insignificant early symptoms, lack of effective diagnostic methods, rapid disease progression, and susceptibility to early lymph node metastasis and distant metastasis. Therefore, comprehensive treatment of PAAD is considered an effective measure to improve the prognosis and survival of patients. Chemotherapy is the most important treatment modality after surgery, and current chemotherapeutic drugs are mainly gemcitabine and fluoropyrimidine drugs.

Gemcitabine can inhibit DNA synthesis and is a first-line chemotherapeutic agent for PAAD, but has some side effects such as nausea, vomiting, elevated transaminases, skin rash, leukocytosis, anemia, thrombocytopenia, dyspnea, alopecia, weakness, proteinuria, and hematuria. Fluorouracil is an antimetabolite with an antiproliferative effect, but its toxicity can induce mucositis, myelosuppression, nausea, vomiting, alopecia, and palmoplantar erythrodermic dysesthesia.[3] Therefore, it is particularly urgent and important to find core therapeutic targets and effective drugs that can inhibit pancreatic adenocarcinoma proliferation, migration, and block angiogenesis. Network pharmacology constructs a "drug-gene-target-disease" network of drugs and diseases based on bioinformatics, molecular biology, and various large databases, revealing the mechanism of traditional Chinese medicine (TCM) in the treatment of diseases systematically and completely. Different from the current "one target, one drug" approach, network pharmacology utilizes the strategy of "network target, multi-component".[4] Network pharmacology can be used to analyze the main active ingredients and potential target genes of plants thereby searching for therapeutic targets against a certain disease. Therefore, it has been widely used in mechanistic studies of TCM for the treatment of complex diseases (such as cancer, asthma, and cardiovascular disease).[5]

With the rapid development of modern biotechnology such as microarray and high-throughput sequencing in recent years, microarray technology combined with bioinformatics analysis has become an effective method for screening tumor target genes at the genomic level.[6] Shivangi Agarwal et al. screened out potential target identification and small molecule inhibitors for breast cancer by bioinformatics methods,[7] while Ting Li, Xujie Gao, and others analyzed hub genes with prognostic value in gastric cancer using the same bioinformatics method.[8] Li et al. predicted anticancer drugs and drug combinations based on bioinformatics of multi-omics data and applied in precision medicine to cancer treatment.[9]

In this study, differentially expressed genes (DEGs) were screened out from the biological information mining of the GEO (gene expression omnibus) database, and key genes were identified and functionally validated, followed by screening the active ingredients and target genes of TCMs through network pharmacology methods. Contrasting the key target genes and Hub genes, potential therapeutic gene targets were obtained. It aims to find therapeutic targets that can inhibit the proliferation and migration of pancreatic adenocarcinoma, so as to provide some help for the diagnosis and treatment of pancreatic adenocarcinoma in the future.


MATERIALS AND METHODS

Data resources

The three gene expression profiles of pancreatic adenocarcinoma (GSE15471, GSE41368, and GSE62165) were obtained from the GEO (gene expression omnibus, https://www.ncbi.nlm.nih.gov/geo/) database. The differential genes between the pancreatic adenocarcinoma tissues and the adjacent normal tissues on the three datasets were screened by the online analysis tool GEO2R, and the original gene expression data and volcanic diagram were obtained.

Data processing

p < 0.05, |Log FC| ≥ 2 was used as the criterion for screening the differentially expressed genes to obtain the differentially expressed genes, and the intersection of the differentially expressed genes in the three datasets was taken by drawing a Venn diagram (http://bioinformatics.psb.ugent.be/webtools/Venn/) to obtain the common differentially expressed genes of the three datasets.

Build PPI (protein-protein interaction) network

PPI analysis of differentially expressed genes was performed using the STRING (Search Tool for the Retrieval of Interacting Genes, https://string-db.org/) online bioanalytical database. The screened differentially expressed genes were input into STRING, set multiple proteins, species select human (Homo sapiens), took default parameters, and removed unrelated proteins to construct a PPI network map.

Screening Hub genes

Cytoscape is a software that can graphically display, analyze and edit network data. It describes the topological relationship between genes through several topological algorithms. The PPI network diagram was visualized by Cytoscape software. The intersection of the first 20 genes was calculated and designated as the Hub gene by CytoHubba plug-in and the PPI was drawn.

GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) enrichment analysis of differentially expressed genes

DAVID database(https://david.ncifcrf.gov)is an important database integrating gene annotation, visualization and comprehensive discovery for high-throughput functional analysis of genes. GO analysis is commonly used in functional enrichment studies and includes three categories: biological process (BP), molecular function (MF) and cellular component (CC). KEGG contains information on genomic biological pathways and system functions, and can systematically analyze gene functions. Enrichment analyses of the GO and KEGG pathways of the obtained differential genes using the DAVID database revealed that FDR < 0.05 and Count ≥ 10 were statistically significant; and visualize GO and KEGG using the GO/KEGG Analysis feature of HIPLOT (https://hiplot.com.cn/basic/r-code-flow).

Hub genes survival curve

The function of Survival Plots was selected in the database of dynamic analysis of gene expression profiling data (http://gepia.cancer-pku.cn, gepia), and overall survival (OS) was used as the indicator. Cancer name selected was ‘pancreatic adenocarcinoma’, and the survival curve diagram of the effect of each HUB gene on OS was drawn. The genes with p < 0.05 in survival analysis were screened out, which were the relevant genes with poor prognosis.

Differential expression of Hub genes in normal tissues and tumors

Box Plots in Expression were selected in the GEPIA database to compare the expression of Hub genes in adjacent normal and pancreatic adenocarcinoma tissues. Interactive web service database, TIMER, was used to draw the immune infiltration map of Hub gene and visually assesses tumor infiltrating immune cells.

Acquisition of active ingredients of traditional Chinese medicine

Using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, four Chinese medicinal materials including Folium Artemisiae Argyi, Semen Ginkgo, Herba Sedi, and Cortex Ailanthi were selected from the related Chinese medicinal materials (Related herbs) of PAAD. Besides, the data of relevant TCM ingredients and target genes were screened out based on ADME (A: absorption, D: distribution, M: metabolism, E: excretion): Oral Bioavailability (OB) ≥ 30% and Drug-Likeness (DL) ≥ 0.18. The collected target names were converted into normalized gene ID names using the protein database Uniprot (https://www.uniprot.org/).

Construction of interaction network between Chinese medicine components and PAAD differentially expressed genes

The intersection targets of PAAD differentially expressed gene targets and TCM active ingredient gene targets were intersected using Venn diagram tool to obtain the intersection targets of both. The intersecting targets were uploaded to the String (https://string-db.org) database for PPI network construction. With the species defined as "Homo sapiens", the remaining parameters were set at default to construct a PPI network model.

Molecular docking verification

Through the PDB (protein data bank) database and zinc (https://zinc.docking.org/substances/home/)databases download the 3D structures of target proteins and active ingredients of TCMs, respectively, taking the former as the receptor and the latter as the ligand for the recognition of intermolecular interactions, predicting the stable binding conformations of molecules and proteins to evaluate the binding strength and activity of the target and the active compound.


RESULTS

Obtaining target gene sets and differentially expressed genes

Among the three datasets obtained from GEO database, 267 DEGs were screened out from GSE15471 datasets, including 47 up-regulated genes and 220 down-regulated genes [Figure 1A]. A total of 950 DEGs were screened out on GSE62165 datasets, including 253 up-regulated genes and 697 down-regulated genes [Figure 1B]. A total of 503 DEGs were screened out on GSE41368 datasets, including 136 up-regulated genes and 367 down-regulated genes [Figure 1C]. After importing all the DEGs into the Venn diagram plotting tool, 133 differentially expressed genes common to the three datasets were obtained, including 104 upregulated DEGs [Figure 1D] and 29 downregulated DEGs [Figure 1E]. And the PPI network was constructed based on the DEGs of the above three datasets [Figure 2], in which green was the upregulated DEGs and red was the downregulated DEGs.

Figure 1.
Figure 1. DEGs obtained from GEO database analysis. (A) DEGs volcano map of GSE41368; (B) DEGs volcano map of GSE62165; (C) DEGs volcano map of GSE15471; (D) Up-regulated genes; (E) Down-regulated genes.

Figure 2.
Figure 2. Protein-Protein Interaction network (PPI) network of 133 DEGs.

Building PPI networks

The obtained 133 differential genes were imported into the STRING database, and the minimum required interaction score was set to 0.4 and concealing free protein nodes in the network to obtain a PPI. Removing free protein nodes, a total of 144 protein node connections formed 522 complex PPI networks [Figure 3].

Figure 3.
Figure 3. Protein-Protein Interaction network (PPI) network of 133 DEGs.

Screening Hub gene

Using the CytoHubba plug-in in Cytoscape to sort the differentially expressed genes according to the Degree value, we screened out 20 Hub genes in the following order: FN1, ALB, EGF, COL3A1, MMP2, LOX, POSTN, TIMP1, FBN1, BGN, VCAN, THBS2, COL5A2, SPARC, MMP1, CXCR4, IGF-BP3, COL12A1, CPA1, CDH11. And a PPI network of the 20 Hub genes was constructed [Figure 4].

Figure 4.
Figure 4. Protein-Protein Interaction network (PPI) network of 20 Hub.

GO and KEGG enrichment analysis of DEGS

GO and KEGG enrichment analysis of DEGs was performed using David, and differential genes were subjected to GO and KEGG visual enrichment analysis using the GO/KEGG analysis function in Hiplot. GO enrichment analysis includes Biological Process (BP), Cellular Component (CC) and Molecular Function (MF). The results of GO analysis showed that most of the DEGs were enriched in extracellular matrix (ECM) organization. In BP, the DEGs were mainly concentrated in ECM organization, extracellular structural tissues and tissue remodeling [Figure 5A]. In CC, the DEGs were mainly concentrated in collagen-containing ECM, endoplasmic reticulum cavity and basement membrane [Figure 5B]. In MF, the DEGs were mainly concentrated in the structural components of ECM, and affected the activities of glycosaminoglycan binding, collagen binding, peptidase inhibitor, serine hydrolase and serine endopeptidase [Figure 5C]. The KEGG enrichment analysis indicated that DEGs was mainly enriched in ECM- receptor interaction, fat digestion and absorption, pancreatic secretion, and protein digestion and absorption [Figure 5D].

Figure 5.
Figure 5. GO and KEGG. (A) Biological Process (BP); (B) Cellular Component (CC); (C) Molecular Function (MF); (D) KEGG.

Survival analysis of Hub gene

Using the survival analysis function of GEPIA2 website, we drew the survival curve of Hub gene and screened out the survival curve of Hub gene with Logrank p value less than 0.05 [Figure 6], indicating that these Hub genes are associated with the prognosis of pancreatic adenocarcinoma. The Hub genes finally screened out were COL12A1, LOX, and MMP1.

Figure 6.
Figure 6. Survival analysis of Hub genes—Overall Survival: (A) COL12A1; (B) LOX; (C) MMP1.

Differential expression of Hub gene in normal tissue and pancreatic adenocarcinoma tissue

Box plots of the differential expression of hub genes in normal and pancreatic adenocarcinoma tissues were drawn using the GEPIA 2 website (Figure 7 shows COL12A1 in Figure A, LOX in Figure B and MMP1 in Figure C). As shown in the figure, the COL12A1, LOX and MMP1 genes are all low expressed in normal tissues, and they are positively correlated with the progression of pancreatic adenocarcinoma in the pancreatic adenocarcinoma tissue. The correlation between differential expression of Hub gene target protein and immune infiltration is shown in Figure 8.

Figure 7.
Figure 7. Expression of Hub genes in normal and glioma tissues (Box Plot): (A) COL12A1; (B) LOX; (C) MMP1.

Figure 8.
Figure 8. Correlation between differential expression of Hub gene target protein and immune infiltration: (A) COL12A1; (B) LOX; (C) MMP1.

Screening of drugs and targets

The active traditional Chinese medicine compound targets satisfying ADME attribute values from Folium Artemisiae Argyi, Semen Ginkgo, Herba Sedi, and Cortex Ailanthi were screened from the TCMSP database. The active TCM compound targets shared by the four TCMs were screened out further [Table 1].

Table 1.
Table 1. Active ingredients of traditional Chinese medicine and their names.

Construction of PPI network of traditional Chinese medicine components-target genes

Differentially expressed genes in pancreatic adenocarcinoma and Chinese medicine targets were put into the Venn diagram tool, and the common intersection targets were screened out by plotting the Venn diagram. Finally obtained intersecting targets include: IGFBP 3, MMP2, MMP1 and EGF. Then, the intersection targets were substituted into the STRING database to construct a PPI network diagram [Figure 9].

Figure 9.
Figure 9. PPI network of Intersection gene.

Screening active components of traditional Chinese medicine

The Cytoscape software was used to construct the active ingredient-core gene interaction network of Chinese materia medica [Figure 10]. From the figure, we can see that MOL000098 is most closely related to the Hub gene. The monomer compound corresponding to MOL000098 is quercetin, and quercetin is the common monomer of the four TCMs.

Figure 10.
Figure 10. Interaction network of active ingredients of traditional Chinese medicine—differential expression target of core genes.

Molecular docking

The intersecting genes of 20 Hub genes and four core genes were taken, and the MMP1 with significantly up-regulated expression and high potential as a drug target was obtained. Using AutoDockTools-1.5.6 and PyMol software, we performed molecular docking between the targeted protein MMP1 and the active ingredient MMP1 of TCM, and the docking binding energy of MMP1 and quercetin was -2.33 kcal / mol, and the hydrogen bonds between quercetin and the amino acid residues SER-263 (length: 2.1 Å), ARG-262 (length: 2.2 Å), GLN-257 (length: 2.2 Å) of MMP1 led to the formation of a more stable complex [Figure 11]. Molecular docking verified that quercetin could directly or indirectly act on key potential targets such as MMP1, which could be used as the pivotal evidence for the inhibitory effect of quercetin on the growth of pancreatic adenocarcinoma and predicted its potential for targeted therapy for pancreatic adenocarcinoma.

Figure 11.
Figure 11. MMP1- quercetin molecular splicing: (A) molecular splicing; (B) spliced hydrogen bond connection.


DISCUSSION

Pancreatic adenocarcinoma is one of the most lethal malignant tumors in the world. Many factors lead to poor prognosis, such as the difficulty in establishing early diagnosis, recurrence, metastasis and resistance to chemotherapy and radiotherapy. Over the past 30 years, the long-term survival rate of patients with PAAD has been very low (as low as 6%).[10] According to a series of tests, about 90% of PAAD cases have distant metastasis.[11] Therefore, finding the target genes that may affect the proliferation and migration of pancreatic adenocarcinoma tissue is very important.

In this study, we obtained the potential DEGs related to pancreatic adenocarcinoma through gene expression and protein-protein expression analysis in GEO database. Then, with a series of bioinformatics tools, we finally obtained three key genes with good prognosis, which may be potential therapeutic targets for pancreatic adenocarcinoma. Using network pharmacology analysis, our study showed that a total of four traditional Chinese medicine components act through four target genes, and are effective anticancer components and targets. The final results showed that MOL000098 was more closely related to the target gene MMP1, and it was most likely to become the active ingredient monomer of Chinese medicine for the treatment of PAAD. MMP1 also has a good prognosis in the treatment of PAAD. The monomer of the effective component of traditional Chinese medicine corresponding to MOL000098 is quercetin.

In recent years, some studies have shown that quercetin has different biological effects,[12] including antiviral, cell cycle regulation, anti-oxidation, angiogenesis inhibition, anti-cancer, apoptosis induction and C-blocking protein kinase.[13],[14] The research indicated that quercetin, as antioxidant, could be used for chemoprevention at low concentration, but quercetin, as prooxidant, could be used for chemotherapy at high concentration.[15]

At present, it is considered that the anticancer effect of quercetin depends on its ability to reduce proliferation, induce apoptosis, cause cell cycle arrest and inhibit mitotic process by regulating cyclin, promoting apoptosis, PI3K/Akt and mitogen activated protein kinase (MAPK).[16] Mitochondrial mediated pathway is considered to be the main mechanism of quercetin induced apoptosis.[17]

Matrix metalloproteinases (MMPs) are various proteolytic enzymes that digest different components of extracellular matrix (ECM). Human fibroblast collagenase (MMP1), as an important member of MMPs family, plays an important role in many physiological and pathological processes, such as atherosclerosis, wound healing, inflammation and carcinogenesis.[18] MMP1 has been identified as a biomarker of bladder cancer,[19] esophageal cancer[20] and lung adenocarcinoma.[21] MMP1 performs several pro-tumor functions by activating protease-activated receptor 1 (PAR1), including promoting tumor metastasis through cross endothelial migration by exerting enhanced endothelial permeability,[22] and inducing protein activation to promote endothelial cell angiogenesis.[23] MMP1 is produced in two different forms of glycosylase, 52 kDa and 57 kDa, and the molecular weight of the active form are 42 kDa and 47 kDa, respectively. The human gene MMP1 is located on chromosome 11, q22.2–22.3.[24] MMP1 is involved not only in the regeneration of collagen fibers in the extracellular space, but also in the cleavage of many non-matrix substrates and cell surface molecules.

The level of MMP1 is usually low in normal human body, but its expression increases during wound healing, repair, or remodeling. More importantly, MMP1 is up-regulated in a variety of advanced cancers, and its expression is directly and negatively correlated with survival. Therefore, down-regulation of MMP1 at all stages of pancreatic adenocarcinoma invasion and metastasis may serve as a target for therapeutic strategy.[24]

As indicated by the GO and KEGG enrichment analysis results, quercetin may target MMP1 to reduce PAAD-induced mortality by enhancing cell adhesion, affecting fatty acid uptake, and Promote apoptosis in cancer cells. Other results reported are also consistent with our findings. Ghafouri-Fard et al.  found that quercetin can inhibit prostate cancer proliferation, increase cancer cell apoptosis, induce cell cycle arrest at G2/M stage, and activate endoplasmic network stress, and the secretion of reactive oxygen species surges.[25] Pang et al. showed that quercetin could affect CD36 and reduce PC mortality by improving cell adhesion.[26]


CONCLUSION

The results showed that quercetin could play a potential therapeutic role by targeting MMP1 to inhibit the proliferation and migration of pancreatic adenocarcinoma, or provide a theoretical basis for future research on therapeutic targets of pancreatic adenocarcinoma.

 

FINANCIAL SUPPORT AND SPONSORSHIP

This work was supported by the Key Research and Development Program of Jiangxi Province (No.20192BBGL70049, to Yongsheng Li).

 

CONFLICTS OF INTEREST

The authors have no conflicts of interest to declare.

 

ETHICS APPROVAL AND CONSENT TO PARTICIPATE

Not applicable.

 

AUTHOR CONTRIBUTIONS

(I) Conception and design: Y Li and H Chen; (II) Administrative support: Y Li; (III) Provision of study materials or patients: Z Zu and H Chen; (IV) Collection and assembly of data: Z Zu and Z Zhu; (V) Data analysis and interpretation: Z Zu and Z Xia; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.


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Anticoagulation might not be necessary for asymptomatic central venous catheter-related thrombosis in adults

Wei Zhang1, Zhi Xiang1, Qin Ma2, Chuanlin Zhang3, Yu Zhao1, Qining Fu1*


The Roles of microRNA in the Diagnosis and Prognosis of Papillary Thyroid Cancer

Jingya Gao1*, Li Liu2*


Lung Cancer Tumor Microenvironment: An Update on Recent Advances in Research

Guangda Yuan1, Bowen Hu1, Yong Yang1*


Quantified ADC Values and Attenuation Trends for Diagnosing Prostate Cancer with Multiple b Values MRI

Jing Hu1#, Jingying Bu1#,Zhe Wang2#, Zhengdan Su2, Xiaoxian Wang2, Haiyao Pi3, Diliang Li2, Zhaoyang Pu4, Xin Tian1*


Differential Expression of T-box Transcription Factor TBX19 Regulates the Progression of Hepatocellular Carcinoma

Guifang He1, Yanjiao Hu2, Fuguo Dong3, Changchang Liu1, Duo Cai1, Shihai Liu1*


Advances in Pathogenesis and Non-surgical Therapy of Cutaneous Basal Cell Carcinoma

Yichen Wu1, Jia Chen2*


Huge Lung Fibroleiomyomatous Hamartoma in the Pleural Cavity – A Case report

Minghui Liu1#, Xin Li1#, Hongbing Zhang1, Fan Ren1, Ming Dong1, Chunqiu Xia1, Jun Chen1,2*


Increased Expression of IL-17A, IL-6, STAT3, TGF-β, and VEGF: Potential Biomarkers in Bladder Cancer?

Zishen Xiao1, Chengxia Bai1, Teng Zhao1, Jiayu Lin1, Lijuan Yang1, Jian Liu2, Zhenjiang Wang1, Ying Sun3,4, Yanbo Liu1*


Identification of NSD2 as a Potential Diagnostic and Prognostic Biomarker for Hepatocellular Carcinoma

Wei Zhao1#, Xinyu Xiao1#, Yu Gao1,2, Shanshan Liu3, Xiuzhen Zhang1, Changhong Yang1, Qiling Peng1, Ning Jiang2*, Jianwei Wang1*


Quercetin Inhibits Glioma Proliferation by Targeting CDK1 and CCNB1 - Bioinformatics and Network Pharmacology

Huaixu Li1#, Peng Gao1#, Haotian Tian1, Zhenyu Han2, Xingliang Dai1*, Hongwei Cheng1*


Selective Internal Radiation Therapy with Yttrium-90 Microspheres in Hepatocellular Carcinoma – Applications and recent advances

Wei Wang1, Dawei Xie1, Bing Li1, Minghao Chen1*


Irreversible Electroporation in Pancreatic Cancer – Applications and recent advances

Yuanyuan Sun1, Qian Li2, Jia Hu2, Yanfang Liu2*, Xiaosong Li2*


Prognostic Value of Bismuth Typing and Modified T‑stage in Hilar Cholangiocarcinoma

Shengen Yi, Xiongjian Cui, Li Xiong, Xiaofeng Deng, Dongni Pei, Yu Wen, Xiongying Miao


MicroRNAs are Related to Rituximab in Combination with Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Resistance in Patients with Diffuse Large B-cell Lymphoma

Haibo Huang1, Junjiao Gu1, Shuna Yao1, Zhihua Yao1, Yan Zhao1, Qingxin Xia2, Jie Ma2, Ling Mai3, Shujun Yang1, Yanyan Liu1


Comparison of Intra-voxel Incoherent Motion Diffusion Magnetic Resonance Imaging and Apparent Diffusion Coefficient in the Evaluation of Focal Malignant Liver Masses

Jinrong Qu1, Xiang Li1, Lei Qin2, Lifeng Wang1, Junpeng Luo1, Jianwei Zhang1, Hongkai Zhang1, Jing Li1, Fei Sun3, Shouning Zhang1, Yanle Li1, Cuicui Liu1, Hailiang Li1


Extracting Breathing Signal Using Fourier Transform from Cine Magnetic Resonance Imaging

Jing Cai1,2, Yilin Liu2, Fangfang Yin1,2


Split End Family RNA Binding Proteins: Novel Tumor Suppressors Coupling Transcriptional Regulation with RNA Processing

Hairui Su1, Yanyan Liu2, Xinyang Zhao1


Thioredoxin-interacting Protein as a Common Regulation Target for Multiple Drugs in Clinical Therapy/Application

Pengxing  Zhang1, Xiaoling Pang2,3, Yanyang Tu1,4


Associations of Age and Chemotherapy with Late Skin and Subcutaneous Tissue Toxicity in a Hypofractionated Adjuvant Radiation Therapy Schedule in Post‑mastectomy Breast Cancer Patients

Mohammad Akram1, Ghufran Nahid1, Shahid Ali Siddiqui1, Ruquiya Afrose2


Monitoring of Disease Activity in Chronic Myeloid Leukemia‑chronic Phase Patients Treated with Indian Generic Veenat (NATCO) Imatinib Mesylate: A Tertiary Care Experience

Khushboo Dewan, Tathagat Chatterjee


Review of Cancer Immunotherapy: Application of Chimeric Antigen Receptor T Cells and Programmed Death 1/Programmed Death‑ligand 1 Antibodies

Tengfei Zhang1,2, Ling Cao1, Zhen Zhang1, Dongli Yue1, Yu Ping1, Hong Li1, Lan Huang1, Yi Zhang1,3,4,5


Systematic Review of MicroRNAs and its Therapeutic Potential in Glioma

Nan Liu1, Yanyang Tu2


The Involvement of p53‑miR‑34a‑CDK4 Signaling During the Development of Cervical Cancer

Huijun Zuo, Jieqi Xiong, Hongwei Chen, Sisun Liu, Qiaoying Gong, Fei Guo


Unusual Clinical Presentation of a Rare Type of Breast Malignancy: A Case Report and a Short Review of Literature

Nadeesha J. Nawarathna1, Navam R. Kumarasinghe1, Palitha Rathnayake2,
Ranjith J. K. Seneviratne1


Sweet’s Syndrome in Acute Lymphoblastic Leukemia with t (9:22)

Khushboo Dewan, Shailaja Shukla


Analysis of the Correlationship between Prostate Specific Antigen Related Variables and Risk Factor in Patients with Prostate Carcinoma

Daoyuan Wang1, Tiejun Yang2, Yongqiang Zou1, Xinqiang Yang1


Recent Progress in Genetic and Epigenetic Profile of Diffuse Gastric Cancer

Zhengxi He1, Bin Li1,2


Strategies for Management of Spinal Metastases: A Comprehensive Review

Zhantao Deng, Bin Xu, Jiewen Jin, Jianning Zhao, Haidong Xu


Application and Perspectives of Traditional Chinese Medicine in the Treatment of Liver Cancer

Xia Mao, Yanqiong Zhang, Na Lin


Primary Hepatic Carcinoid Tumor: A Case Report and Literature Review

Yupeng Lei1, Hongxia Chen2, Pi Liu1, Xiaodong Zhou1


Expression Characteristics of miR‑10b in Nasopharyngeal Carcinoma

Gang Li, Yunteng Zhao, Jianqi Wang, Haoran Huang, Mengwen Zhang


An Update on Immunohistochemistry in Translational Cancer Research

Zonggao Shi, M. Sharon Stack


Promoter Methylated Tumor Suppressor Genes in Glioma

Yingduan Cheng1, Yanyang Tu2, Pei Liang3


Palliative Treatment of Malignant Pleural Effusion

Chenyang Liu1*, Qian Qian2*, Shen Geng1, Wenkui Sun1, Yi Shi1


Functional Perspective and Implications of Gene Expression by Noncoding RNAs

Xiaoshuang Yan1, Huanyu Xu2, Zhonghai Yan3


Expression of E3 Ubiquitin Ligases in Multiple Myeloma Patients after Treatment with the Proteasome Inhibitor Bortezomib

James Joseph Driscoll


miR‑505 Downregulates 6‑Phosphofructo‑2‑Kinase/ Fructose‑2,6‑Biphosphatase 4 to Promote Cell Death in Glioblastoma

Esther H. Chung, Hongwei Yang, Hongyan Xing, Rona S. Carroll, Mark D. Johnson


Utility of Fine Needle Aspiration Cytology in Diagnosing Bone Tumors

Sonal Mahajan1, Akash Arvind Saoji2, Anil Agrawal1


Histone H2A and H2B Deubiquitinase in Developmental Disease and Cancer

Demeng Chen1, Caifeng Dai2, Yizhou Jiang3


Genetic Characteristics of Glioblastoma: Clinical Implications of Heterogeneity

Qian Li1, Yanyang Tu1,2


Acute Lymphoblastic Leukemia with Normal Platelet Count

Khushboo Dewan, Kiran Agarwal


Galanin is a Novel Epigenetic Silenced Functional Tumor Suppressor in Renal Cell Carcinoma

Shengkun Sun1*, Axiang Xu1*, Guoqiang Yang1, Yingduan Cheng2

 


Selenium Dioxide Induced Apoptosis in Cervical Cancer Cells via Regulating Apoptosis-related Let-7a MicroRNA and Proteins

Sisun Liu1, Jieqi Xiong2, Ling Guo3, Min Xiu1,4, Feng He1,4, Yuanlei Lou5, Fei Guo6,7


Low Expression of Polo‑like Kinase 1 is Associated with Poor Prognosis in Liver Cancer

Weixia Li1, Kunpeng Liu1, Dechen Lin2, Xin Xu2, Haizhen Lu3, Xinyu Bi4, Mingrong Wang2


Extracorporeal Photopheresis for Steroid‑refractory Chronic Graft‑versus‑host Disease After Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta‑Analysis

Runzhe Chen1, Baoan Chen1, Peter Dreger2, Michael Schmitt2, Anita Schmitt2


Glucans and Cancer: Historical Perspective

Petr Sima1, Luca Vannucci1, Vaclav Vetvicka2


Implications of Circadian Rhythm Regulation by microRNAs in Colorectal Cancer

Song Wu1, Andrew Fesler2, Jingfang Ju2


BCL2 Family, Mitochondrial Apoptosis, and Beyond

Haiming Dai1, X. Wei Meng2, Scott H. Kaufmann2


Quantum Dot‑based Immunohistochemistry for Pathological Applications

Li Zhou1, Jingzhe Yan2, Lingxia Tong3, Xuezhe Han4, Xuefeng Wu5, Peng Guo6


CD24 as a Molecular Marker in Ovarian Cancer: A Literature Review

Lu Huang1, Weiguo Lv2, Xiaofeng Zhao1


Etiological Trends in Oral Squamous Cell Carcinoma: A Retrospective Institutional Study

Varsha Salian, Chethana Dinakar, Pushparaja Shetty, Vidya Ajila


Effect of Irinotecan Combined with Cetuximab on Liver Function in Patients with Advanced Colorectal Cancer with Liver Metastases

Yan Liang1, Yang Li2, Xin Li3, Jianfu Zhao4


The Role of Precision Medicine in Pancreatic Cancer: Challenges for Targeted Therapy, Immune Modulating Treatment, Early Detection, and Less Invasive Operations

Khaled Kyle Wong1, Zhirong Qian2, Yi Le3


Targeting Signal Transducer and Activator of Transcription 3 for Colorectal Cancer Prevention and Treatment with Natural Products

Weidong Li1,2*, Cihui Chen3*, Zheng Liu2, Baojin Hua1


The Potential of Wnt Signaling Pathway in Cancer: A Focus on Breast Cancer

Mahnaz M. Kazi, Trupti I. Trivedi, Toral P. Kobawala, Nandita R. Ghosh


Imaging‑driven Digital Biomarkers

Enrico Capobianco


Target‑Matching Accuracy in Stereotactic Body Radiation Therapy of Lung Cancer: An Investigation Based on Four‑Dimensional Digital Human Phantom

Jing Cai1,2, Kate Turner2, Xiao Liang2, W. Paul Segars2,3, Chris R. Kelsey1, David Yoo1, Lei Ren1,2, Fang‑Fang Yin1,2


Downregulation of Death‑associated Protein Kinase 3 and Caspase‑3 Correlate to the Progression and Poor Prognosis of Gliomas

Ye Song, Tianshi Que, Hao Long, Xi’an Zhang, Luxiong Fang, Zhiyong Li, Songtao Qi


Hyaluronic Acid in Normal and Neoplastic Colorectal Tissue: Electrospray Ionization Mass Spectrometric and Fluor Metric Analysis

Ana Paula Cleto Marolla1, Jaques Waisberg2, Gabriela Tognini Saba2, Demétrius Eduardo Germini2, Maria Aparecida da Silva Pinhal1


Melanoma Antigen Gene Family in the Cancer Immunotherapy

Fengyu Zhu1, Yu Liang1, Demeng Chen2, Yang Li1


Combined Chronic Lymphocytic Leukemia and Pancreatic Neuroendocrine Carcinoma: A Collision Tumor Variation

Kaijun Huang1, Panagiotis J. Vlachostergios1, Wanhua Yang2, Rajeev L. Balmiki3


Antiproliferative and Apoptotic Effect of Pleurotus ostreatus on Human Mammary Carcinoma Cell Line (Michigan Cancer Foundation‑7)

Krishnamoorthy Deepalakshmi, Sankaran Mirunalini


Impact of Age on the Biochemical Failure and Androgen Suppression after Radical Prostatectomy for Prostate Cancer in Chilean Men

Nigel P. Murray1,2, Eduardo Reyes1,3, Nelson Orellana1, Cynthia Fuentealba1, Omar Jacob1


Carcinoma of Unknown Primary: 35 Years of a Single Institution’s Experience

Rana I. Mahmood1,2, Mohammed Aldehaim1,3, Fazal Hussain4, Tusneem A. Elhassan4,
Zubeir A. Khan5, Muhammad A. Memon6


Metformin in Ovarian Cancer Therapy: A Discussion

Yeling Ouyang1, Xi Chen2, Chunyun Zhang1, Vichitra Bunyamanop1, Jianfeng Guo3


The Progress in Molecular Biomarkers of Gliomas

Jing Qi1, Hongwei Yang2, Xin Wang2, Yanyang Tu1


Correlation between Paclitaxel Tc > 0.05 and its Therapeutic Efficacy and Severe Toxicities in Ovarian Cancer Patients

Shuyao Zhang1*, Muyin Sun2*, Yun Yuan3*, Miaojun Wang4*, Yuqi She1*, Li Zhou5, Congzhu Li5, Chen Chen1, Shengqi Zhang4


Identifying Gaps and Relative Opportunities for Discovering Membrane Proteomic Biomarkers of Triple‑negative Breast Cancer as a Translational Priority

Bhooma Venkatraman


The Molecular Mechanism and Regulatory Pathways of Cancer Stem Cells

Zhen Wang1, Hongwei Yang2, Xin Wang2, Liang Wang3, Yingduan Cheng4, Yongsheng Zhang5, Yanyang Tu1,2


Nanoparticle Drug Delivery Systems and Three‑dimensional Cell Cultures in Cancer Treatments and Research

Wenjin Shi1, Ding Weng2,3, Wanting Niu2,3


Choline Kinase Inhibitors Synergize with TRAIL in the Treatment of Colorectal Tumors and Overcomes TRAIL Resistance

Juan Carlos Lacal1, Ladislav Andera2


MicroRNA Regulating Metabolic Reprogramming in Tumor Cells: New Tumor Markers

Daniel Otero‑Albiol, Blanca Felipe‑Abrio


Biomarkers of Colorectal Cancer: A Genome‑wide Perspective

José M. Santos‑Pereira1, Sandra Muñoz‑Galván2


Nicotinamide Adenine Dinucleotide+ Metabolism Biomarkers in Malignant Gliomas

Manuel P. Jiménez‑García, Eva M. Verdugo‑Sivianes, Antonio Lucena‑Cacace


Patient-derived Xenografts as Models for Personalized Medicine Research in Cancer

Marco Perez, Lola Navas, Amancio Carnero


Genome‑wide Transcriptome Analysis of Prostate Cancer Tissue Identified Overexpression of Specific Members of the Human Endogenous Retrovirus‑K Family

Behnam Sayanjali1,2


Clinical Utility of Interleukin‑18 in Breast Cancer Patients: A Pilot Study

Reecha A. Parikh, Toral P. Kobawala, Trupti I. Trivedi, Mahnaz M. Kazi, Nandita R. Ghosh


Current and Future Systemic Treatment Options for Advanced Soft‑tissue Sarcoma beyond Anthracyclines and Ifosfamide

Nadia Hindi1,2, Javier Martin‑Broto1,2


The Genomic Organization and Function of IRX1 in Tumorigenesis and Development

Pengxing Zhang1, Hongwei Yang2, Xin Wang2, Liang Wang3, Yingduan Cheng4, Yongsheng Zhang5, Yanyang Tu1,2


Stem Cell‑based Approach in Diabetes and Pancreatic Cancer Management

Yi‑Zhou Jiang1, Demeng Chen2


Mutation Detection with a Liquid Biopsy 96 Mutation Assay in Cancer Patients and Healthy Donors

Aaron Yun Chen, Glenn D. Braunstein, Megan S. Anselmo, Jair A. Jaboni, Fernando Troy Viloria, Julie A. Neidich, Xiang Li, Anja Kammesheidt


The Application of Estrogen Receptor‑1 Mutations’ Detection through Circulating Tumor DNA in Breast Cancer

Binliang Liu, Yalan Yang, Zongbi Yi, Xiuwen Guan, Fei Ma


Circulating MicroRNAs and Long Noncoding RNAs: Liquid Biomarkers in Thoracic Cancers

Pablo Reclusa1, Anna Valentino1, Rafael Sirera1,2, Martin Frederik Dietrich3, Luis Estuardo Raez3, Christian Rolfo1


Exosomes Biology: Function and Clinical Implications in Lung Cancer

Martin Frederik Dietrich1, Christian Rolfo2, Pablo Reclusa2, Marco Giallombardo2, Anna Valentino2, Luis E. Raez1


Circulating Tumor DNA: A Potential Biomarker from Solid Tumors’ Monitor to Anticancer Therapies

Ting Chen1,2, Rongzhang He1,3, Xinglin Hu1,3,4, Weihao Luo1, Zheng Hu1,3, Jia Li1, Lili Duan1, Yali Xie1,2, Wenna Luo1,2, Tan Tan1,2, Di‑Xian Luo1,2


Novel Molecular Multilevel Targeted Antitumor Agents

Poonam Sonawane1, Young A. Choi1, Hetal Pandya2, Denise M. Herpai1, Izabela Fokt3,
Waldemar Priebe3, Waldemar Debinski1


Fish Oil and Prostate Cancer: Effects and Clinical Relevance

Pei Liang, Michael Gao Jr.


Stemness‑related Markers in Cancer

Wenxiu Zhao1, Yvonne Li2, Xun Zhang1


Autophagy Regulated by miRNAs in Colorectal Cancer Progression and Resistance

Andrew Fesler1, Hua Liu1, Ning Wu1,2, Fei Liu3, Peixue Ling3, Jingfang Ju1,3


Gastric Metastases Mimicking Primary Gastric Cancer: A Brief Literature Review

Simona Gurzu1,2,3, Marius Alexandru Beleaua1, Laura Banias2, Ioan Jung1


Possibility of Specific Expression of the Protein Toxins at the Tumor Site with Tumor‑specialized Promoter

Liyuan Zhou1,2, Yujun Li1,2, Changchen Hu3, Binquan Wang1,2


SKI‑178: A Multitargeted Inhibitor of Sphingosine Kinase and Microtubule Dynamics Demonstrating Therapeutic Efficacy in Acute Myeloid Leukemia Models

Jeremy A. Hengst1,2, Taryn E. Dick1,2, Arati Sharma1, Kenichiro Doi3, Shailaja Hegde4, Su‑Fern Tan5, Laura M. Geffert1,2, Todd E. Fox5, Arun K. Sharma1, Dhimant Desai1, Shantu Amin1, Mark Kester5, Thomas P. Loughran5, Robert F. Paulson4, David F. Claxton6, Hong‑Gang Wang3, Jong K. Yun1,2


A T‑cell Engager‑armed Oncolytic Vaccinia Virus to Target the Tumor Stroma

Feng Yu1, Bangxing Hong1, Xiao‑Tong Song1,2,3


Real‑world Experience with Abiraterone in Metastatic Castration‑resistant Prostate Cancer

Yasar Ahmed1, Nemer Osman1, Rizwan Sheikh2, Sarah Picardo1, Geoffrey Watson1


Combination of Interleukin‑11Rα Chimeric Antigen Receptor T‑cells and Programmed Death‑1 Blockade as an Approach to Targeting Osteosarcoma Cells In vitro

Hatel Rana Moonat, Gangxiong Huang, Pooja Dhupkar, Keri Schadler, Nancy Gordon,
Eugenie Kleinerman


Efficacy and Safety of Paclitaxel‑based Therapy and Nonpaclitaxel‑based Therapy in Advanced Gastric Cancer

Tongwei Wu, Xiao Yang, Min An, Wenqin Luo, Danxian Cai, Xiaolong Qi


Motion Estimation of the Liver Based on Deformable Image Registration: A Comparison Between Four‑Dimensional‑Computed Tomography and Four‑Dimensional-Magnetic Resonance Imaging

Xiao Liang1, Fang‑Fang Yin1,2, Yilin Liu1, Brian Czito2, Manisha Palta2, Mustafa Bashir3, Jing Cai1,2


A Feasibility Study of Applying Thermal Imaging to Assist Quality Assurance of High‑Dose Rate Brachytherapy

Xiaofeng Zhu1, Yu Lei1, Dandan Zheng1, Sicong Li1, Vivek Verma1, Mutian Zhang1, Qinghui Zhang1, Xiaoli Tang2, Jun Lian2, Sha X. Chang2, Haijun Song3, Sumin Zhou1, Charles A. Enke1


Role of Exosome microRNA in Breast Cancer

Wang Qu, Ma Fei, Binghe Xu


Recent Progress in Technological Improvement and Biomedical Applications of the Clustered Regularly Interspaced Short Palindromic Repeats/Cas System

Yanlan Li1,2*, Zheng Hu1*, Yufang Yin3, Rongzhang He1, Jian Hu1, Weihao Luo1, Jia Li1, Gebo Wen2, Li Xiao1, Kai Li1, Duanfang Liao4, Di-Xian Luo1,5


The Significance of Nuclear Factor‑Kappa B Signaling Pathway in Glioma: A Review

Xiaoshan Xu1, Hongwei Yang2, Xin Wang2, Yanyang Tu1


Markerless Four‑Dimensional‑Cone Beam Computed Tomography Projection‑Phase Sorting Using Prior Knowledge and Patient Motion Modeling: A Feasibility Study

Lei Zhang1,2, Yawei Zhang2, You Zhang1,2,3, Wendy B. Harris1,2, Fang‑Fang Yin1,2,4, Jing Cai1,4,5, Lei Ren1,2


The Producing Capabilities of Interferon‑g and Interleukin‑10 of Spleen Cells in Primary and Metastasized Oral Squamous Cell Carcinoma Cells-implanted Mice

Yasuka Azuma1,2, Masako Mizuno‑Kamiya3, Eiji Takayama1, Harumi Kawaki1, Toshihiro Inagaki4, Eiichi Chihara2, Yasunori Muramatsu5, Nobuo Kondoh1


“Eating” Cancer Cells by Blocking CD47 Signaling: Cancer Therapy by Targeting the Innate Immune Checkpoint

Yi‑Rong Xiang, Li Liu


Glycosylation is Involved in Malignant Properties of Cancer Cells

Kazunori Hamamura1, Koichi Furukawa2


Biomarkers in Molecular Epidemiology Study of Oral Squamous Cell Carcinoma in the Era of Precision Medicine

Qing‑Hao Zhu1*, Qing‑Chao Shang1*, Zhi‑Hao Hu1*, Yuan Liu2, Bo Li1, Bo Wang1, An‑Hui Wang1


I‑Kappa‑B Kinase‑epsilon Activates Nuclear Factor‑kappa B and STAT5B and Supports Glioblastoma Growth but Amlexanox Shows Little Therapeutic Potential in These Tumors

Nadège Dubois1, Sharon Berendsen2, Aurélie Henry1,2, Minh Nguyen1, Vincent Bours1,
Pierre Alain Robe1,2


Suppressive Effect of Mesenchymal Stromal Cells on Interferon‑g‑Producing Capability of Spleen Cells was Specifically Enhanced through Humoral Mediator(s) from Mouse Oral Squamous Cell Carcinoma Sq‑1979 Cells In Vitro

Toshihiro Inagaki1,2, Masako Mizuno‑Kamiya3, Eiji Takayama1, Harumi Kawaki1, Eiichi Chihara4, Yasunori Muramatsu5, Shinichiro Sumitomo5, Nobuo Kondoh1


An Interplay Between MicroRNA and SOX4 in the Regulation of Epithelial–Mesenchymal Transition and Cancer Progression

Anjali Geethadevi1, Ansul Sharma2, Manish Kumar Sharma3, Deepak Parashar1


MicroRNAs Differentially Expressed in Prostate Cancer of African‑American and European‑American Men

Ernest K. Amankwah


The Role of Reactive Oxygen Species in Screening Anticancer Agents

Xiaohui Xu1, Zilong Dang2, Taoli Sun3, Shengping Zhang1, Hongyan Zhang1


Panobinostat and Its Combination with 3‑Deazaneplanocin‑A Induce Apoptosis and Inhibit In vitro Tumorigenesis and Metastasis in GOS‑3 Glioblastoma Cell Lines

Javier de la Rosa*, Alejandro Urdiciain*, Juan Jesús Aznar‑Morales, Bárbara Meléndez1,
Juan A. Rey2, Miguel A. Idoate3, Javier S. Castresana


Cancer Stem‑Like Cells Have Cisplatin Resistance and miR‑93 Regulate p21 Expression in Breast Cancer

Akiko Sasaki1, Yuko Tsunoda2, Kanji Furuya3, Hideto Oyamada1, Mayumi Tsuji1, Yuko Udaka1, Masahiro Hosonuma1, Haruna Shirako1, Nana Ichimura1, Yuji Kiuchi1


The Contribution of Hexokinase 2 in Glioma

Hui Liu1, Hongwei Yang2, Xin Wang3, Yanyang Tu1


The Mechanism of BMI1 in Regulating Cancer Stemness Maintenance, Metastasis, Chemo‑ and Radiation Resistance

Xiaoshan Xu, Zhen Wang, Nan Liu, Pengxing Zhang, Hui Liu, Jing Qi, Yanyang Tu


A Multisource Adaptive Magnetic Resonance Image Fusion Technique for Versatile Contrast Magnetic Resonance Imaging

Lei Zhang1,2, Fang‑Fang Yin1,2,3, Brittany Moore1,2, Silu Han1,2, Jing Cai1,2,4


Senescence and Cancer

Sulin Zeng1,2, Wen H. Shen2, Li Liu1


The “Wild”‑type Gastrointestinal Stromal Tumors: Heterogeneity on Molecule Characteristics and Clinical Features

Yanhua Mou1, Quan Wang1, Bin Li1,2


Retreatment with Cabazitaxel in a Long‑Surviving Patient with Castration‑Resistant Prostate Cancer and Visceral Metastasis

Raquel Luque Caro, Carmen Sánchez Toro, Lucia Ochoa Vallejo


Therapy‑Induced Histopathological Changes in Breast Cancers: The Changing Role of Pathology in Breast Cancer Diagnosis and Treatment

Shazima Sheereen1, Flora D. Lobo1, Waseemoddin Patel2, Shamama Sheereen3,
Abhishek Singh Nayyar4, Mubeen Khan5


Glioma Research in the Era of Medical Big Data

Feiyifan Wang1, Christopher J. Pirozzi2, Xuejun Li1


Transarterial Embolization for Hepatocellular Adenomas: Case Report and Literature Review

Jian‑Hong Zhong1,2, Kang Chen1, Bhavesh K. Ahir3, Qi Huang4, Ye Wu4, Cheng‑Cheng Liao1, Rong‑Rong Jia1, Bang‑De Xiang1,2, Le‑Qun Li1,2


Nicotinamide Phosphoribosyltransferase: Biology, Role in Cancer, and Novel Drug Target

Antonio Lucena‑Cacace1,2,3, Amancio Carnero1,2


Enhanced Anticancer Effect by Combination of Proteoglucan and Vitamin K3 on Bladder Cancer Cells

Michael Zhang, Kelvin Zheng, Muhammad Choudhury, John Phillips, Sensuke Konno


Molecular Insights Turning Game for Management of Ependymoma: A Review of Literature

Ajay Sasidharan, Rahul Krishnatry


IDH Gene Mutation in Glioma

Leping Liu1, Xuejun Li1,2


Challenges and Advances in the Management of Pediatric Intracranial Germ Cell Tumors: A Case Report and Literature Review

Gerard Cathal Millen1, Karen A. Manias1,2, Andrew C. Peet1,2, Jenny K. Adamski1


Assessing the Feasibility of Using Deformable Registration for Onboard Multimodality‑Based Target Localization in Radiation Therapy

Ge Ren1,2,3, Yawei Zhang1,2, Lei Ren1,2


Research Advancement in the Tumor Biomarker of Hepatocellular Carcinoma

Qing Du1, Xiaoying Ji2, Guangjing Yin3, Dengxian Wei3, Pengcheng Lin1, Yongchang Lu1,
Yugui Li3, Qiaohong Yang4, Shizhu Liu5, Jinliang Ku5, Wenbin Guan6, Yuanzhi Lu7


Novel Insights into the Role of Bacterial Gut Microbiota in Hepatocellular Carcinoma

Lei Zhang1, Guoyu Qiu2, Xiaohui Xu2, Yufeng Zhou3, Ruiming Chang4


Central Odontogenic Fibroma with Unusual Presenting Symptoms

Aanchal Tandon, Bharadwaj Bordoloi, Safia Siddiqui, Rohit Jaiswal


The Prognostic Role of Lactate in Patients Who Achieved Return of Spontaneous Circulation after Cardiac Arrest: A Systematic Review and Meta‑analysis

Dongni Ren1, Xin Wang2, Yanyang Tu1,2


Inhibitory Effect of Hyaluronidase‑4 in a Rat Spinal Cord Hemisection Model

Xipeng Wang1,2, Mitsuteru Yokoyama2, Ping Liu3


Research and Development of Anticancer Agents under the Guidance of Biomarkers

Xiaohui Xu1, Guoyu Qiu1, Lupeng Ji2, Ruiping Ma3, Zilong Dang4, Ruling Jia1, Bo Zhao1


Idiopathic Hypereosinophilic Syndrome and Disseminated Intravascular Coagulation

Mansoor C. Abdulla


Phosphorylation of BRCA1‑Associated Protein 1 as an Important Mechanism in the Evasion of Tumorigenesis: A Perspective

Guru Prasad Sharma1, Anjali Geethadevi2, Jyotsna Mishra3, G. Anupa4, Kapilesh Jadhav5,
K. S. Vikramdeo6, Deepak Parashar2


Progress in Diagnosis and Treatment of Mixed Adenoneuroendocrine Carcinoma of Biliary‑Pancreatic System

Ge Zengzheng1, Huang-Sheng Ling2, Ming-Feng Li2, Xu Xiaoyan1, Yao Kai1, Xu Tongzhen3,
Ge Zengyu4, Li Zhou5


Surface-Enhanced Raman Spectroscopy to Study the Biological Activity of Anticancer Agent

Guoyu Qiu1, Xiaohui Xu1, Lupeng Ji2, Ruiping Ma3, Zilong Dang4, Huan Yang5


Alzheimer’s Disease Susceptibility Genes in Malignant Breast Tumors

Steven Lehrer1, Peter H. Rheinstein2


OSMCC: An Online Survival Analysis Tool for Merkel Cell Carcinoma

Umair Ali Khan Saddozai1, Qiang Wang1, Xiaoxiao Sun1, Yifang Dang1, JiaJia Lv1,2, Junfang Xin1, Wan Zhu3, Yongqiang Li1, Xinying Ji1, Xiangqian Guo1


Protective Activity of Selenium against 5‑Fluorouracil‑Induced Nephrotoxicity in Rats

Elias Adikwu, Nelson Clemente Ebinyo, Beauty Tokoni Amgbare


Advances on the Components of Fibrinolytic System in Malignant Tumors

Zengzheng Ge1, Xiaoyan Xu1, Zengyu Ge2, Shaopeng Zhou3, Xiulin Li1, Kai Yao1, Lan Deng4


A Patient with Persistent Foot Swelling after Ankle Sprain: B‑Cell Lymphoblastic Lymphoma Mimicking Soft‑tissue Sarcoma

Crystal R. Montgomery‑Goecker1, Andrew A. Martin2, Charles F. Timmons3, Dinesh Rakheja3, Veena Rajaram3, Hung S. Luu3


Coenzyme Q10 and Resveratrol Abrogate Paclitaxel‑Induced Hepatotoxicity in Rats

Elias Adikwu, Nelson Clemente Ebinyo, Loritta Wasini Harris


Progress in Clinical Follow‑up Study of Dendritic Cells Combined with Cytokine‑Induced Killer for Stomach Cancer

Ling Wang1,2, Run Wan1,2, Cong Chen1,2, Ruiliang Su1,2, Yumin Li1,2


Supraclavicular Lymphadenopathy as the Initial Manifestation in Carcinoma of Cervix

Priyanka Priyaarshini1, Tapan Kumar Sahoo2


ABO Typing Error Resolution and Transfusion Support in a Case of an Acute Leukemia Patient Showing Loss of Antigen Expression

Debasish Mishra1, Gopal Krushna Ray1, Smita Mahapatra2, Pankaj Parida2


Protein Disulfide Isomerase A3: A Potential Regulatory Factor of Colon Epithelial Cells

Yang Li1, Zhenfan Huang2, Haiping Jiang3


Clinicopathological Association of p16 and its Impact on Outcome of Chemoradiation in Head‑and‑Neck Squamous Cell Cancer Patients in North‑East India

Srigopal Mohanty1, Yumkhaibam Sobita Devi2, Nithin Raj Daniel3, Dulasi Raman Ponna4,
Ph. Madhubala Devi5, Laishram Jaichand Singh2


Potential Inhibitor for 2019‑Novel Coronaviruses in Drug Development

Xiaohui Xu1, Zilong Dang2, Lei Zhang3, Lingxue Zhuang4, Wutang Jing5, Lupeng Ji6, Guoyu Qiu1


Best‑Match Blood Transfusion in Pediatric Patients with Mixed Autoantibodies

Debasish Mishra1, Dibyajyoti Sahoo1, Smita Mahapatra2, Ashutosh Panigrahi3


Characteristics and Outcome of Patients with Pheochromocytoma

Nadeema Rafiq1, Tauseef Nabi2, Sajad Ahmad Dar3, Shahnawaz Rasool4


Comparison of Histopathological Grading and Staging of Breast Cancer with p53‑Positive and Transforming Growth Factor‑Beta Receptor 2‑Negative Immunohistochemical Marker Expression Cases

Palash Kumar Mandal1, Anindya Adhikari2, Subir Biswas3, Amita Giri4, Arnab Gupta5,
Arindam Bhattacharya6


Chemical Compositions and Antiproliferative Effect of Essential Oil of Asafoetida on MCF7 Human Breast Cancer Cell Line and Female Wistar Rats

Seyyed Majid Bagheri1,2, Davood Javidmehr3, Mohammad Ghaffari1, Ehsan Ghoderti‑Shatori4


Cyclooxygenase‑2 Contributes to Mutant Epidermal Growth Factor Receptor Lung Tumorigenesis by Promoting an Immunosuppressive Environment

Mun Kyoung Kim1, Aidin Iravani2, Matthew K. Topham2,3


Potential role of CircMET as A Novel Diagnostic Biomarker of Papillary Thyroid Cancer

Yan Liu1,2,3,4#, Chen Cui1,2,3,4#, Jidong Liu1,2,3,4, Peng Lin1,2,3,4,Kai Liang1,2,3,4, Peng Su5, Xinguo Hou1,2,3,4, Chuan Wang1,2,3,4, Jinbo Liu1,2,3,4, Bo Chen6, Hong Lai1,2,3,4, Yujing Sun1,2,3,4* and Li Chen 1,2,3,4*


Cuproptosis-related Genes in Glioblastoma as Potential Therapeutic Targets

Zhiyu Xia1,2, Haotian Tian1, Lei Shu1,2, Guozhang Tang3, Zhenyu Han4, Yangchun Hu1*, Xingliang Dai1*


Cancer Diagnosis and Treatments by Porous Inorganic Nanocarriers

Jianfeng Xu1,2, Hanwen Zhang1,2, Xiaohui Song1,2, Yangong Zheng3, Qingning Li1,2,4*


Delayed (20 Years) post-surgical Esophageal Metastasis of Breast Cancer - A Case Report

Bowen Hu1#, Lingyu Du2#, Hongya Xie1, Jun Ma1, Yong Yang1*, Jie Tan2*


Subtyping of Undifferentiated Pleomorphic Sarcoma and Its Clinical Meaning

Umair Ali Khan Saddozai, Zhendong Lu, Fengling Wang, Muhammad Usman Akbar, Saadullah Khattak, Muhammad Badar, Nazeer Hussain Khan, Longxiang Xie, Yongqiang Li, Xinying Ji, Xiangqian Guo


Construction of Glioma Prognosis Model and Exploration of Related Regulatory Mechanism of Model Gene

Suxia Hu, Abdusemer Reyimu, Wubi Zhou, Xiang Wang, Ying Zheng, Xia Chen, Weiqiang Li, Jingjing Dai


ESRP2 as a Non-independent Potential Biomarker-Current Progress in Tumors

Yuting Chen, Yuzhen Rao, Zhiyu Zeng, Jiajie Luo, Chengkuan Zhao, Shuyao Zhang


Resection of Bladder Tumors at the Ureteral Orifice Using a Hook Plasma Electrode: A Case Report

Jun Li, Ziyong Wang, Qilin Wang


Structural Characterization and Bioactivity for Lycium Barbarum Polysaccharides

Jinghua Qi1,2,  Hangping Chen3,Huaqing Lin2,4,Hongyuan Chen1,2,5* and Wen Rui2,3,5,6*


The Role of IL-22 in the Prevention of Inflammatory Bowel Disease and Liver Injury

Xingli Qi1,2, Huaqing Lin2,3, Wen Rui2,3,4,5 and Hongyuan Chen1,2,3


RBM15 and YTHDF3 as Positive Prognostic Predictors in ESCC: A Bioinformatic Analysis Based on The Cancer Genome Atlas (TCGA)

Yulou Luo1, Lan Chen2, Ximing Qu3, Na Yi3, Jihua Ran4, Yan Chen3,5*


Mining and Analysis of Adverse Drug Reaction Signals Induced by Anaplastic Lymphoma Kinase-Tyrosine Kinase Inhibitors Based on the FAERS Database

Xiumin Zhang1,2#, Xinyue Lin1,3#, Siman Su1,3#, Wei He3, Yuying Huang4, Chengkuan Zhao3, Xiaoshan Chen3, Jialin Zhong3, Chong Liu3, Wang Chen3, Chengcheng Xu3, Ping Yang5, Man Zhang5, Yanli Lei5*, Shuyao Zhang1,3*


Advancements in Immunotherapy for Advanced Gastric Cancer

Min Jiang1#, Rui Zheng1#, Ling Shao1, Ning Yao2, Zhengmao Lu1*


Tumor Regression after COVID-19 Infection in Metastatic Adrenocortical Carcinoma Treated with Immune Checkpoint Blockade: A Case Report

Qiaoxin Lin1, Bin Liang1, Yangyang Li2, Ling Tian3*, Dianna Gu1*


Mining and Analysis of Adverse Events of BRAF Inhibitors Based on FDA Reporting System

Silan Peng1,2#, Danling Zheng1,3#, Yanli Lei4#, Wang Chen3, Chengkuan Zhao3, Xinyue Lin1, Xiaoshan Chen3, Wei He3, Li Li3, Qiuzhen Zhang5*, Shuyao Zhang1,3*


Malignant Phyllodes Tumor with Fever, Anemia, Hypoproteinemia: A Rare and Strange Case Report and Literature Review

Zhenghang Li1, Yuxian Wei1*


Construction of Cuproptosis-Related LncRNA Signature as a Prognostic Model Associated with Immune Microenvironment for Clear-Cell Renal Cell Carcinoma

Jiyao Yu1#, Shukai Zhang2#, Qingwen Ran3, Xuemei Li4,5,6*


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