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Pyogenic liver abscess as initial presentation in locally advanced right colon cancer invading the liver

Kai Qu, Chang Liu, Aasef M A Mansoor, Bo Wang, Jincai Chen, Liang Yu, Yi Lv

《医学前沿（英文）》 2011年 第5卷 第4期   页码 434-437 doi: 10.1007/s11684-011-0157-3

摘要： Locally advanced colorectal cancer complicated with adjacent organic invasion may remain confined to the local area with minimal metastasis. In the present paper, we report on a patient with advanced right colon cancer, including liver, gallbladder, and duodenal invasion behind the scene of liver abscess. resection was performed on the patient, with right-hemicolectomy, cholecystectomy, partial duodental resection, and hepatectomy. Postoperative management was administered, including nutritional support in the early postoperative period, effective anti-infection treatment, and adjuvant chemotherapy (FOLFOX4). The patient survived for 16 months after the operation. Common clinical manifestations of colorectal cancer were digestive symptoms and changes in defecation. However, the clinical manifestation of locally advanced colon cancer was extremely complicated. Extended or multivisceral resection may offer patients a chance to survive an acute crisis and allow for treatment with adjuvant therapy.

关键词： liver abscess     locally advanced colon cancer     multiorganic invasion    

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Bioinformatic exploration of MTA1-regulated gene networks in colon cancer

null

《医学前沿（英文）》 2016年 第10卷 第2期   页码 178-182 doi: 10.1007/s11684-016-0442-2

摘要：

Metastasis-associated gene 1 (MTA1) controls a series of biological processes in tumor progression. Tumor progression is a complex process regulated by a gene network. The global cancer gene regulatory network must be analyzed to determine the position of MTA1 in the molecular network and its cooperative genes by further exploring the biological functions of this gene. We used TCGA data sets and GeneCards database to screen MTA1-related genes. GO and KEGG pathway analyses were conducted with DAVID and gene network analysis via STRING and Cytoscape. Results showed that in the development of colon cancer, MTA1 is linked to certain signal pathways, such as Wnt/Notch/nucleotide excision repair pathways. The findings also suggested that MTA1 demonstrates the closest relationship in a coregulation process with the key molecules AKT1, EP300, CREBBP, SMARCA4, RHOA, and CAD. These results lead MTA1 exploration to an in-depth investigation in different directions, such as Wnt, Notch, and DNA repair.

关键词： metastasis-associated gene 1     colon cancer     bioinformatics    

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G protein-coupled receptor LGR6 is an independent risk factor for colon adenocarcinoma

Wenjing Wang, Shigang Ding, Hejun Zhang, Jun Li, Jun Zhan, Hongquan Zhang

《医学前沿（英文）》 2019年 第13卷 第4期   页码 482-491 doi: 10.1007/s11684-018-0633-0

摘要： LGR6 is a member of the G protein-coupled receptor family that plays a tumor-suppressive role in colon cancer. However, the relationship between LGR6 expression in patients and clinicopathological factors remains unclear. This study aimed to clarify whether the expression level of LGR6 is correlated with colon adenocarcinoma progression. Immunohistochemistry was used to detect LGR6 expression in colon adenoma tissues ( = 21), colon adenocarcinoma tissues ( = 156), and adjacent normal tissues ( = 124). The expression levels of LGR6 in colon adenoma and adenocarcinoma were significantly higher than those in normal colon epithelial tissues ( <0.001). Low LGR6 expression predicted a short overall survival in patients with colon adenocarcinoma (log-rank test, = 0.016). Univariate and multivariate survival analyses showed that, in addition to N and M classification, LGR6 expression served as an independent prognostic factor. Thus, low expression of LGR6 can be used as an independent prognostic parameter in patients with colon adenocarcinoma.

关键词： LGR6     colon adenocarcinoma     immunohistochemistry     prognosis    

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结直肠癌、基质和正常结肠黏膜显微解剖区域N-糖组的显著多样性 Article

Di Wang, Katarina Madunić , Tao Zhang, Guinevere S.M. Lageveen-Kammeijer, Manfred Wuhrer

《工程（英文）》 2023年 第26卷 第7期   页码 32-43 doi: 10.1016/j.eng.2022.08.016

摘要：

Aberrant glycosylation is considered to be a hallmark of colorectal cancer (CRC), as demonstrated by various studies. While the N-glycosylation of cell lines and serum has been widely examined, the analysis of cancer-associated N-glycans from tissues has been hampered by the heterogeneity of tumors and the complexity of N-glycan structures. To overcome these obstacles, we present a study using laser capture microdissection that makes it possible to largely deconvolute distinct N-glycomic signatures originating from different regions of heterogeneous tissues including cancerous, stromal, and healthy mucosa cells. N-glycan alditols were analyzed by means of porous graphitized carbon liquid chromatography-electrospray ionization tandem mass spectrometry, enabling the differentiation and structural characterization of isomeric species. In total, 116 N-glycans were identified that showed profound differences in expression among cancer, stroma, and normal mucosa. In comparison with healthy mucosa, the cancer cells showed an increase in α2-6 sialylation and monoantennary N-glycans, as well as a decrease in bisected N-glycans. Moreover, specific sialylated and (sialyl-)LewisA/X antigen-carrying N-glycans were exclusively expressed in cancers. In comparison with cancer, the stroma showed lower levels of oligomannosidic and monoantennary N-glycans, LewisA/X epitopes, and sulfation, as well as increased expression of (core-)fucosylation and α2-3 sialylation. Our study reveals the distinct N-glycomic profiles of different cell types in CRC tumor and control tissues, proving the necessity of their separate analysis for the discovery of cancer-associated glycans.

 

关键词： 结直肠癌     肿瘤     多孔石墨化碳液相色谱-质谱     N-糖组     抗体反应    

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Expression of STAT6 and NF-κB p65 in the colon mucosa of patients with ulcerative colitis

Rui ZHU MD, Heng FAN MD, Lin SHEN MD, Jianguo LIU BD, Jia ZHAO MM,

《医学前沿（英文）》 2009年 第3卷 第4期   页码 475-479 doi: 10.1007/s11684-009-0086-6

摘要： The expression of signal transducer and activator of transcription 6 (STAT6) and nuclear factor-κB (NF-κB) in the colonic mucosa of patients with ulcerative colitis (UC) was examined. Real-time polymerase chain reaction and immunohistochemistry were used to detect the expression of STAT6 and NF-κB p65 at both mRNA and protein levels in the colonic mucosa of patients with UC and healthy volunteers. The results showed that the expression levels of STAT6 and NFκB p65 in the colonic mucosa of patients with UC were significantly higher than in normal controls at both mRNA and protein levels. These data suggest that STAT6 and NFκB p65 perhaps play an important role in the pathogenesis of UC and underscore the potential value of anti-UC strategies in the clinical management of this disease.

关键词： ulcerative colitis     signal transducer and activator of transcription 6 (STAT6)     nuclear factor-κ     B p65 (NF-κ     B p65)    

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Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer

《医学前沿（英文）》 2021年 第15卷 第6期   页码 942-942 doi: 10.1007/s11684-021-0876-z

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Progress and challenges in RET-targeted cancer therapy

《医学前沿（英文）》 2023年 第17卷 第2期   页码 207-219 doi: 10.1007/s11684-023-0985-y

摘要： The rearranged during transfection (RET) is a receptor protein tyrosine kinase. Oncogenic RET fusions or mutations are found most often in non-small cell lung cancer (NSCLC) and in thyroid cancer, but also increasingly in various types of cancers at low rates. In the last few years, two potent and selective RET protein tyrosine kinase inhibitors (TKIs), pralsetinib (BLU-667) and selpercatinib (LOXO-292, LY3527723) were developed and received regulatory approval. Although pralsetinib and selpercatinib gave high overall response rates (ORRs), < 10% of patients achieved a complete response (CR). The RET TKI-tolerated residual tumors inevitably develop resistance by secondary target mutations, acquired alternative oncogenes, or MET amplification. RET G810 mutations located at the kinase solvent front site were identified as the major on-target mechanism of acquired resistance to both selpercatinib and pralsetinib. Several next-generation of RET TKIs capable of inhibiting the selpercatinib/pralsetinib-resistant RET mutants have progressed to clinical trials. However, it is likely that new TKI-adapted RET mutations will emerge to cause resistance to these next-generation of RET TKIs. Solving the problem requires a better understanding of the multiple mechanisms that support the RET TKI-tolerated persisters to identify a converging point of vulnerability to devise an effective co-treatment to eliminate the residual tumors.

关键词： pralsetinib     selpercatinib     RET-alteration     lung cancer     thyroid cancer     tumor-agnostic therapy     drug resistance    

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Epithelial-to-mesenchymal transition in cancer: complexity and opportunities

Yun Zhang, Robert A. Weinberg

《医学前沿（英文）》 2018年 第12卷 第4期   页码 361-373 doi: 10.1007/s11684-018-0656-6

摘要：

The cell-biological program termed the epithelial-to-mesenchymal transition (EMT) plays an important role in both development and cancer progression. Depending on the contextual signals and intracellular gene circuits of a particular cell, this program can drive fully epithelial cells to enter into a series of phenotypic states arrayed along the epithelial-mesenchymal phenotypic axis. These cell states display distinctive cellular characteristics, including stemness, invasiveness, drug-resistance and the ability to form metastases at distant organs, and thereby contribute to cancer metastasis and relapse. Currently we still lack a coherent overview of the molecular and biochemical mechanisms inducing cells to enter various states along the epithelial-mesenchymal phenotypic spectrum. An improved understanding of the dynamic and plastic nature of the EMT program has the potential to yield novel therapies targeting this cellular program that may aid in the management of high-grade malignancies.

关键词： epithelial-to-mesenchymal transition     cancer     metastasis     cancer stem cell    

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Metformin for cancer prevention

Yonghua Yang

《医学前沿（英文）》 2011年 第5卷 第2期   页码 115-117 doi: 10.1007/s11684-011-0112-3

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Orlistat induces ferroptosis-like cell death of lung cancer cells

《医学前沿（英文）》 2021年 第15卷 第6期   页码 922-932 doi: 10.1007/s11684-020-0804-7

摘要： Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers, including lung cancer; however, targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need. In this study, we tested the anticancer activity of orlistat, an FDA-approved anti-obesity drug, in human and mouse cancer cells in vitro and in vivo, and we found that orlistat, as a single agent, inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro. Mechanistically, we found that orlistat reduced the expression of GPX4, a central ferroptosis regulator, and induced lipid peroxidation. In addition, we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2, a molecule regulating the lipid droplet homeostasis, as a novel target of orlistat. Moreover, in a mouse xenograft model, orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control (P<0.05). Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.

关键词： orlistat     ferroptosis     FAF2     lung cancer    

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Role of the forkhead transcription factor FOXO-FOXM1 axis in cancer and drug resistance

null

《医学前沿（英文）》 2012年 第6卷 第4期   页码 376-380 doi: 10.1007/s11684-012-0228-0

摘要：

The forkhead transcription factors FOXO and FOXM1 have pivotal roles in tumorigenesis and in mediating chemotherapy sensitivity and resistance. Recent research shows that the forkhead transcription factor FOXM1 is a direct transcriptional target repressed by the forkhead protein FOXO3a, a vital downstream effector of the PI3K-AKT-FOXO signaling pathway. Intriguingly, FOXM1 and FOXO3a also compete for binding to the same gene targets, which have a role in chemotherapeutic drug action and sensitivity. An understanding of the role and regulation of the FOXO-FOXM1 axis will impact directly on our knowledge of chemotherapeutic drug action and resistance in patients, and provide new insights into the design of novel therapeutic strategy and reliable biomarkers for prediction of drug sensitivity.

关键词： FOXO3a     FOXM1     transcription factor     cancer     drug resistance     tumorigenesis    

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Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic

《医学前沿（英文）》 doi: 10.1007/s11684-023-1050-6

摘要： Pancreatic cancer, notorious for its late diagnosis and aggressive progression, poses a substantial challenge owing to scarce treatment alternatives. This review endeavors to furnish a holistic insight into pancreatic cancer, encompassing its epidemiology, genomic characterization, risk factors, diagnosis, therapeutic strategies, and treatment resistance mechanisms. We delve into identifying risk factors, including genetic predisposition and environmental exposures, and explore recent research advancements in precursor lesions and molecular subtypes of pancreatic cancer. Additionally, we highlight the development and application of multi-omics approaches in pancreatic cancer research and discuss the latest combinations of pancreatic cancer biomarkers and their efficacy. We also dissect the primary mechanisms underlying treatment resistance in this malignancy, illustrating the latest therapeutic options and advancements in the field. Conclusively, we accentuate the urgent demand for more extensive research to enhance the prognosis for pancreatic cancer patients.

关键词： pancreatic cancer     cancer screening     single cell     molecular alterations     precancerous lesion     therapy resistance    

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Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future

《医学前沿（英文）》 2023年 第17卷 第1期   页码 18-42 doi: 10.1007/s11684-022-0976-4

摘要： With the improved understanding of driver mutations in non-small cell lung cancer (NSCLC), expanding the targeted therapeutic options improved the survival and safety. However, responses to these agents are commonly temporary and incomplete. Moreover, even patients with the same oncogenic driver gene can respond diversely to the same agent. Furthermore, the therapeutic role of immune-checkpoint inhibitors (ICIs) in oncogene-driven NSCLC remains unclear. Therefore, this review aimed to classify the management of NSCLC with driver mutations based on the gene subtype, concomitant mutation, and dynamic alternation. Then, we provide an overview of the resistant mechanism of target therapy occurring in targeted alternations (“target-dependent resistance”) and in the parallel and downstream pathways (“target-independent resistance”). Thirdly, we discuss the effectiveness of ICIs for NSCLC with driver mutations and the combined therapeutic approaches that might reverse the immunosuppressive tumor immune microenvironment. Finally, we listed the emerging treatment strategies for the new oncogenic alternations, and proposed the perspective of NSCLC with driver mutations. This review will guide clinicians to design tailored treatments for NSCLC with driver mutations.

关键词： non-small cell lung cancer     driver mutations     treatment strategy     resistant mechanism     immune-checkpoint inhibitors    

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Low-dose CT for lung cancer screening: opportunities and challenges

null

《医学前沿（英文）》 2018年 第12卷 第1期   页码 116-121 doi: 10.1007/s11684-017-0600-1

摘要：

Lung cancer is among the most frequently diagnosed cancers worldwide and the leading cause of cancer death in both males and females. Screening for lung cancer coupled with earlier intervention has long been studied as an approach to mortality reduction. However, minimal progress was achieved until recently, when low-dose spiral computed tomography (LDCT) screening demonstrated a 20% reduction in mortality from lung cancer in a randomized controlled trial (RCT), the National Lung Screening Trial, from the United States. On the basis of this finding, LDCT has been recommended for lung cancer screening in high-risk populations by several clinical guidelines. However, results from the following independent RCTs in Europe failed to show consistent conclusions. In addition, intractable problems gradually emerged with the progress of LDCT screening. This paper summarizes and discusses the main observations and challenges of LDCT screening for lung cancer. Before spreading implementation of LDCT screening, challenges, including high false-positive rates, overdiagnosis, enormous costs, and radiation risk, must be addressed. Complementary biomarkers and technical improvement are expected in the field of lung cancer screening in the near future.

关键词： lung cancer     low-dose computerized tomography     early detection     opportunities     challenges    

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Developments in cancer prevention and treatment using traditional Chinese medicine

Hongsheng Lin, Jie Liu, Ying Zhang

《医学前沿（英文）》 2011年 第5卷 第2期   页码 127-133 doi: 10.1007/s11684-011-0137-7

摘要： Through the joint efforts of several generations of practitioners in traditional Chinese medicine (TCM) and integrated medicine of oncology, we have made some achievements in cancer treatment using TCM in over 50 years, including treatment concepts, methods, and basic and clinical research. Currently, TCM plays an indispensable role in cancer prevention and treatment. However, we also clearly recognize that there are some issues that have yet to be resolved. In the future, cancer treated with TCM will face unprecedented opportunities and challenges. This article reviews the developments of TCM in the treatment of cancer.

关键词： traditional Chinese medicine (TCM)     cancer    

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标题 作者 时间 类型 操作

Pyogenic liver abscess as initial presentation in locally advanced right colon cancer invading the liver

Kai Qu, Chang Liu, Aasef M A Mansoor, Bo Wang, Jincai Chen, Liang Yu, Yi Lv

期刊论文

Bioinformatic exploration of MTA1-regulated gene networks in colon cancer

null

期刊论文

G protein-coupled receptor LGR6 is an independent risk factor for colon adenocarcinoma

Wenjing Wang, Shigang Ding, Hejun Zhang, Jun Li, Jun Zhan, Hongquan Zhang

期刊论文

结直肠癌、基质和正常结肠黏膜显微解剖区域N-糖组的显著多样性

Di Wang, Katarina Madunić , Tao Zhang, Guinevere S.M. Lageveen-Kammeijer, Manfred Wuhrer

期刊论文

Expression of STAT6 and NF-κB p65 in the colon mucosa of patients with ulcerative colitis

Rui ZHU MD, Heng FAN MD, Lin SHEN MD, Jianguo LIU BD, Jia ZHAO MM,

期刊论文

Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer

期刊论文

Progress and challenges in RET-targeted cancer therapy

期刊论文

Epithelial-to-mesenchymal transition in cancer: complexity and opportunities

Yun Zhang, Robert A. Weinberg

期刊论文

Metformin for cancer prevention

Yonghua Yang

期刊论文

Orlistat induces ferroptosis-like cell death of lung cancer cells

期刊论文

Role of the forkhead transcription factor FOXO-FOXM1 axis in cancer and drug resistance

null

期刊论文

Improving the prognosis of pancreatic cancer: insights from epidemiology, genomic alterations, and therapeutic

期刊论文

Treatment of advanced non-small cell lung cancer with driver mutations: current applications and future

期刊论文

Low-dose CT for lung cancer screening: opportunities and challenges

null

期刊论文

Developments in cancer prevention and treatment using traditional Chinese medicine

Hongsheng Lin, Jie Liu, Ying Zhang

期刊论文