Leupaxin: A Prospective Therapeutic Target for Esophageal Squamous Carcinoma Treatment
0
Citation
60
Reference
10
Related Paper
Abstract:
Abstract Esophageal squamous cell carcinoma (ESCC) is a prevalent malignant tumor. Immunotherapy research has led to advances in its treatment, but further research is necessary to identify its effective biomarkers. This study investigated the expression, pathological and prognostic significance, protein interactions, pathway enrichment, immune microenvironment, correlations between immune regulators and infiltration of immune cells, associations with drug resistance genes, and chemosensitivity of the immune-related biomarker leupaxin (LPXN) in ESCC using bioinformatics. The relative expression levels of LPXN mRNA and protein were evaluated and verified in both healthy and ESCC tissues using quantitative polymerase chain reaction and immunohistochemistry. The potential role of LPXN in ESCC was investigated using cell proliferation, apoptosis, clonogenic, and migration assays. The co-expression of LPXN and programmed cell death-ligand 1 (PD-L1) at the protein level in ESCC lines was determined by western blotting. We validated the expression of the LPXN gene in ESCC using clinical samples and investigated the correlation between LPXN gene expression and the efficacy of immune therapy for ESCC. Functional experiments demonstrated that inhibiting LPXN led to decreased cell proliferation, increased apoptosis, and impaired cell migration and invasion in ESCC cells. Our results indicate the involvement of the immune-related biomarker LPXN in the proliferation and migration processes of ESCC, establishing a novel framework for treatment.bcl-2 암유전자는 여러 가지 자극에 의한 apoptosis를 차단함으로써 유전자 이상을 가진 세포가 계속 생존하면서 유전자 변이가 누적되는 결과를 초래한다고 알려져 있다. 한편 c-myc 암유전자는 세포증식과 apoptosis를 유도하는 이중적 기능을 가지고 있으며 생존 신호가 결여될 경우에는 오히려 세포의 apoptosis를 유발한다고 알려져 있다. 그러나 c-myc과 bcl-2가 동시에 발현되면 bcl-2는 c-myc의 세포증식 작용은 영향을 주지 않고 apoptosis만을 선택적으로 차단함으로써 유전자 변이 세포의 생존 뿐만 아니라 증식을 촉진하는 것으로 관찰되었다. 자궁경부암에서 c-myc과 bcl-2 발현에 관한 개별적 보고는 있었으나 이들 두 유전자의 동시발현 및 이들 유전자들이 실제 암조직상에서 세포증식 및 apoptosis에 어떠한 영향을 미치는가에 관한 연구는 보고된 것이 없다. 따라서 본 연구에서는 자궁경부암 발생 과정중에서 bcl-2 및 c-myc 발현과 세포증식, apoptosis와의 상관관계를 알아보고자 하였다. 본 연구에서는 10개의 정상 자궁경부조직, 30개의 자궁경부 상피내종양 조직, 20개의 자궁경부암조직에서 bcl-2와 c-myc에 대한 면역조직화학 검사를 시행하였으며 세포증식과 apoptosis는 각각 Ki-67 면역조직화학적 방법과 TUNEL 방법으로 확인하였다. 또한 환자의 임상병리학적 인자들과의 상관관계도 알아보았다. 정상 자궁경부, 자궁경부 상피내종양, 자궁경부암조직 중 자궁경부암조직에서만 bcl-2와 c-myc 단백이 각각 35%와 50%에서 관찰되었으며, 또한 bcl-2와 c-myc의 동시발현이 25%에서 관찰되었다. 세포증식 지수(상피세포 100개중 Ki-67양성 세포수)는 정상 자궁경부, 상피내종양, 자궁경부암으로 진행되면서 10.2, 24.1, 59.7, 71.2로 유의하게 증가하는 양상을 보였으며(p<0.01), apoptosis 지수(상피세포 100개중 apoptosis 세포수)도 0, 0.33, 1.85, 3.89로 점차 증가하는 양상을 보였다(p<0.01). 또한 세포증식 지수와 apoptosis 지수와는 높은 상관관계(r=0.7451, p=0.0002)를 나타내었다. 그러나 자궁경부암 조직중 bcl-2 발현군과 비발현군간에 apoptosis지수에는 차이가 없었으며(p=0.4765), c-myc 발현군과 비발현군간에도 세포증식 지수에는 차이가 없었다(p=0.6891). 또한 bcl-2와 c-myc의 동시 발현군과 나머지 군간에도 증식지수와 apoptosis 지수에 차이가 없었다(각각 p=0.6311 및 p=0.7600). 한편 bcl-2와 c-myc의 동시 발현과 잘 알려져 있는 자궁경부암의 임상병리학적 예후인자들(종양 크기, FIGO 임상병기, 림프절 전이등)과는 유의한 상관관계가 없었다. 이상과 같은 결과에서 자궁경부암발생 과정에서 세포증식과 apoptosis는 병변의 등급과 비례하여 증가하고 apoptosis는 세포증식과 관련된 변화로 사료되었다. 한편 bcl-2와 c-myc과 발현은 자궁경부암에서만 관찰되는 유전자 변이로서 자궁경부 상피내종양의 발생과 진행과정에는 영향을 미치지 않으며, 또한 자궁경부암 조직에서도 암조직 전체의 세포증식 및 apoptosis와는 관련이 없을 것으로 사료되었다.
Cite
Citations (0)
瞄准：学习是否消炎痛(IND )(NS ) ，一个非选择的 cyclooxygenase (艇长) 禁止者或 NS-398，一个 COX-2-selective 禁止者，在人的结肠癌房间导致 apoptosis 并且 apoptosis 相关的基因和小径它被包含。方法：人的结肠癌 Caco-2 房间与也被对待：安慰剂， IND (0.05-0.5 mmol/L ) 或为 1， 5 和 18 h 的 NS (0.01-0.2 mmol/L ) 。我们然后学习了：(1 ) 由 TUNEL 方法的细胞死亡，(2 ) 用 DNA 微数组的 96 apoptosis 相关的基因的 mRNA 表示，(3 ) 选择 apoptosis 的表示由西方的弄污联系了蛋白质。结果：IND 和 NS 以一种剂量依赖者方式在 Caco-2 房间的 30%-50% 导致了 apoptosis。IND (为 1 h 的 0.1 mmol/L ) 在四个家庭的显著地起来调整的 pro-apoptotic 基因：(1 ) TNF 受体和 ligand，(2 ) Caspase，(3 ) Bcl-2 并且(4 ) Caspase 招募领域。NS 治疗起来调整的类似的 pro-apoptotic 基因作为 IND。另外，国际机场家庭的 IND 也下面调整的 anti-apoptotic 基因。结论：(1 ) 非选择并且在以一种剂量依赖者方式的结肠癌房间的 COX-2-selective NSAID induce apoptosis。(2 ) 两 NSAID 由激活二条主要 apoptotic 小径导致 apoptosis：死亡受体小径(包含的 TNF-R ) 和 mitochondrial 小径。(3 ) IND 由起来调整的 pro-apoptotic 基因和下面调整的 anti-apoptotic 基因导致 apoptosis，当时 NS 仅仅起来调整 pro-apoptotic 基因。(4 ) 在由 NSAID 的结肠癌房间的 apoptosis 的正式就职可以部分地解释，他们结肠癌生长上的禁止的行动。
Caspase 8
Intrinsic apoptosis
Cite
Citations (0)
Immunohistochemistry (IHC) is the technique of assessing the expressed protein in vivo through antigen-antibody reaction. In this technique, a more expressed protein is darkly stained than a less expressed one. Immunohistochemistry (IHC) is a technique that involves histological, immunological, and biochemical techniques. IHC with both direct (involving primary antibody) and indirect (involving both primary and secondary antibodies) methods was discussed. A detailed protocol for IHC has been discussed with practical examples of IHC as conducted in our laboratory of growth hormone in pituitary gland, and CD4 and CD8 expressions in uterus. The basic steps for IHC include fixing and embedding the tissue; cutting and mounting the section; deparaffinizing and rehydrating the section; antigen retrieval; immunohistochemical staining; counterstaining (if desired); dehydrating and stabilizing with mounting medium; and viewing the staining under the microscope.
Antigen retrieval
Cite
Citations (26)
Cite
Citations (5)
Immunohistochemistry has become an important tool in research and in surgical pathology. Rapid growth of a new methods in immunohistochemistry supplement traditional histochemical and histological light microscopy investigations. Immunohistochemistry has given pathologists a chance to location different antigens on the cell surface as well as in the cell compartments. The expression of antigens are mostly influenced by factors connected with tissue processing; fixation and embedding. The aim of present article is to show the role of these factors and their influence on some immunohistochemical staining results. Not all the problems are discussed here, the main goal which authors would like to obtain is to show the way how to solve problems which can occur during immunohistochemical staining procedure. They want also to delineate the importance of standardization in immunohistochemistry to make the results more reliable between different laboratories.
Cite
Citations (1)
Immunohistochemistry [IHC] is an important application of monoclonal as well as polyclonal antibodies to determine the tissue distribution of an antigen [protein or lipid] by specific antigen/antibody reaction tagged with a visible label. Immunohistochemistry has an expanding role in diagnostic and research laboratories. This article highlights the various applications of IHC in health and diseases and gives more information in the Future directions of immunohistochemistry.
Polyclonal antibodies
Histopathology
Histology
Cite
Citations (2)
Objective To discuss the application o immunohistochemistry autostainer in immunohistochemistry.Methods More than 30 kinds of first antibodies of the Pathology Department,such as AAT,CerBb-2,CK,HBcAg,ER,PR,Ki-67,and unified second antibodies were selected.Immunohistochemistry autostainer and manual operation were applied to the staining of the antibodies,and then the results by the above methods were compared.Results The antibodies stained by immunohistochemistry autostainer,gifted with clear background,no edge effect,uniform staining and accurate positive results,were all better than those by manual operation from all aspects.Conclusion Immunohistochemistry autostainer is highly automatic,time-saving,manpower-saving,repeatable and highly standardized.
Cite
Citations (0)
In the diagnosis of clinical pathology,immunohistochemistry(IHC) is a very important technology and tools.The immunohistochemical technique used in the pathological diagnosis started the 1970s,pathologist diagnosis of tumor classification,prognosis had a huge impact,but also extends the understanding of the people for various diseases and tumor formationpathological diagnosis and research..However,with the extensive application of immunohistochemistry,the immunohistochemical technique have some limitations.In-depth study of the principles and techniques of immunohistochemistry,familiar with all kinds of really positive antibody reaction site,and inter-laboratory standardization of immunohistochemistry,play the largest role in support of immunohistochemistry in the pathological diagnosis.This article on the above issues as follows.
Cite
Citations (0)
Cite
Citations (3)
Immunohistochemistry (IHC) is an important application of monoclonal as well as polyclonal antibodies to determine the tissue distribution of an antigen of interest in health and disease. IHC is widely used for diagnosis of cancers; specific tumor antigens are expressed de novo or up-regulated in certain cancers. This article deals with the various applications of IHC in diagnosis of diseases, with IHC playing an important role in diagnostic and research laboratories.
Polyclonal antibodies
Cite
Citations (185)