BACKGROUND Among all solid tumors,pancreatic ductal adenocarcinoma(PDAC)is charac-terized by markedly poor survival outcomes,reflecting its high lethality,primarily as a result of late-stage diagnosis and limited trea...BACKGROUND Among all solid tumors,pancreatic ductal adenocarcinoma(PDAC)is charac-terized by markedly poor survival outcomes,reflecting its high lethality,primarily as a result of late-stage diagnosis and limited treatment options.Pancreatic adenocarcinoma upregulated factor(PAUF)displays elevated expression in PDAC compared to non-neoplastic pancreatic samples and is involved in promoting tumor development.However,its exact diagnostic and prognostic significance remains unclear.This study aimed to assess the clinical relevance of PAUF expression in PDAC.We hypothesized that higher PAUF expression is associated with more aggressive clinicopathological features and poorer patient outcomes.AIM To investigate the expression of PAUF in PDAC and its value as a diagnostic and prognostic biomarker.METHODS PAUF expression levels were assessed using immunohistochemistry in tumor tissues from 93 patients with PDAC.Staining intensity and the proportion of tumor cells showing PAUF positivity were assessed to categorize patients into low and high PAUF expression groups.Associations between PAUF expression and clinicopathological characteristics or survival outcomes were analyzed.Public datasets(The Cancer Genome Atlas,Genotype-Tissue Expression,and Clinical Proteomic Tumor Analysis Consortium)were employed to validate differences in PAUF expression in PDAC at mRNA and protein levels.RESULTS PAUF expression was observed in 82.8%of samples,primarily localized within the cytoplasm of tumor cells.High PAUF expression showed a significant correlation with metastasis to lymph nodes(78.4%,P=0.0019),indicating a strong association with advanced disease.Public datasets confirmed elevated PAUF levels at both transcript and protein levels in PDAC relative to normal tissue.Kaplan-Meier estimates indicated that higher PAUF levels were linked with shorter overall survival(18.4 months vs 32.7 months,P=0.032).Multivariate Cox regression confirmed high PAUF expression as a prognostically significant variable contributing to poor clinical outcomes[hazard ratio(HR)=2.05;P=0.009].Poor tumor differentiation(HR=2.47;P=0.004)and lack of adjuvant therapy(HR=0.39;P=0.001)were also independently associated with unfavorable outcomes.CONCLUSION PAUF is a promising biomarker for tumor progression and prognosis in PDAC,with potential clinical utility in early diagnosis and the development of targeted therapies.展开更多
This study investigates the variability in cancer diagnosis across different tissues and organs, with a focus on the role of diagnostic methods such as Hematoxylin and Eosin (H&E) staining and immunohistochemistry...This study investigates the variability in cancer diagnosis across different tissues and organs, with a focus on the role of diagnostic methods such as Hematoxylin and Eosin (H&E) staining and immunohistochemistry (IHC). The predominance of female breast cancer (30%) aligns with global trends, underscoring the need for robust diagnostic protocols, particularly in developing regions. Other prevalent cancers, including skin, stomach, and cervix uteri, reflect a mix of environmental, genetic, and infectious factors. The underrepresentation of gallbladder and thyroid cancers (<1%) suggests potential underdiagnosis or lower prevalence. Age distribution data indicate peak cancer incidence in individuals aged 31 - 45 years, with gender-specific cancers like breast and cervical cancer predominantly affecting females (63.4%). The analysis also highlights significant diagnostic gaps, as 61.2% of cases did not undergo IHC testing due to resource constraints, leading to potential biases in cancer prevalence and diagnostic accuracy. The study emphasizes the complementary role of IHC in confirming ambiguous H&E findings, with strong alignment observed when both methods were used. However, the absence of IHC in many cases limits the robustness of conclusions, suggesting the need for increased access to IHC testing. The findings advocate for integrating IHC into routine diagnostics, expanding diagnostic capabilities, and improving sample sizes to ensure more reliable and comprehensive cancer data.展开更多
BACKGROUND Although thymopoietin(TMPO)has been elucidated to be overexpressed in cancers,its underlying mechanisms are not yet fully understood.AIM To investigate the expression and clinical significance of TMPO in pa...BACKGROUND Although thymopoietin(TMPO)has been elucidated to be overexpressed in cancers,its underlying mechanisms are not yet fully understood.AIM To investigate the expression and clinical significance of TMPO in papillary thyroid carcinoma(PTC).METHODS Databases such as Gene Expression Omnibus,The Cancer Genome Atlas Proand summary receiver operating characteristic curves were plotted to evaluate diagnostic performance.A Gene Set Enrichment Analysis enrichment analysis was conducted to identify TMPO-related signaling pathways.A protein interaction network was constructed to identify hub genes.The impact of TMPO on PTC cell proliferation and the effects of its knockout were analyzed using clustered regularly interspaced short palindromic repeats(CRISPR)knockout screening and the Cancer Cell Line Encyclopedia database.RESULTS The TMPO protein was significantly overexpressed in PTC tissues,primarily localized in the cytoplasm and nuclear membrane.The mRNA level analysis showed mild overexpression of TMPO in PTC tissues,with a certain discriminatory value(area under the curve=0.66).TMPO may promote cancer through involvement in cell adhesion,focal adhesion,leukocyte migration,and multiple cancer-related signaling pathways.Additionally,CRISPR gene knockout experiments confirmed that TMPO knockout significantly inhibited the proliferation of PTC cell lines,indicating its important role in tumor growth.CONCLUSION TMPO is overexpressed in PTC and may serve as a therapeutic target and molecular biomarker for PTC.展开更多
AIM： To study the endoscopic, pathological and immunoo histochemical features of esophageal mesenchymal tumors. METHODS： Twenty-nine patients diagnosed as esophageal rnysenchymal tumors by electronic endoscopy and e...AIM： To study the endoscopic, pathological and immunoo histochemical features of esophageal mesenchymal tumors. METHODS： Twenty-nine patients diagnosed as esophageal rnysenchymal tumors by electronic endoscopy and endoscopic ultrasound （EUS） were observed under light microscopes, and all tissues were stained by the immunohistochemical method. The expression of CD117, CD34, SMA and desmin were measured by staining intensity of cells and positive cell ratios. RESULTS： Endoscopically, esophageal gastrointestinal stromal tumors （GISTs） and leiomyomas （LMs） had similar appearances, showing submucosal protuberant lesions. They all showed low echo images originated from the muscularis propria or muscularis mucosa on EUS. Endoscopy and EUS could not exactly differentiate esophageal GISTs from LMs. Microscopically, there were two kinds of cells： spindle cell type and epitheloid cell type in esophageal GISTs. Leiomyomas and leiomyosarcornas were only of spindle cell type. One malignancy was found in five cases of esophageal GISTs, and one malignancy in 24 cases of leiomyomas and leiomyosarcomas. Using Fisher＇s exact method, the differences of malignant lesion proportion were not significant between esophageal LMs and GISTs, 1/5 vs 1/24 （P 〉 0.05）. All cases of esophageal GISTs were positive for CD117, and 3 cases were also positive for CD34. The 24 cases of leiomyomas and leiomyosarcomas were all negative for CD117 and CD34. The differences of positive rates of CD117 and CD34 were significant between esophageal GISTs and LMs, 5/5 vs 0/24, 3/5 vs 0/24 （P 〈 0.005）. All leiomyomas and leiomyosarcomas were positive for SMA, and desmin. Among 5 cases of esophageal GISTs, 2 cases were SMA positive, and 1 case was desmin positive. The differences in positive rates and expression intensity of SMA and desmin were significant between esophageal LMs and GISTs, 24/24 vs 2/5, 24/24 vs 115 （P 〈 0.005）. CONCLUSION： The most common esophageal mesenchymal tumors are leiomyomas, and esophageal GISTs are less common. Most of esophageal LMs and GISTs are benign. Endoscopy and EUS are the effective methods to diagnose esophageal mesenchymal tumors and they can provide useful information for the treatment of these tumors. However, they cannot exactly differentiate esophageal GISTs from LMs. Pathological, especially immunohistochemical features are useful to differentiate GISTs from leiomyomas.展开更多
AIM:To assess the role of IgM and IgG immunohistochemistry(IHC) in the evaluation of autoimmune liver conditions-autoimmune hepatitis(AIH),primary biliary cirrhosis(PBC),and primary sclerosing cholangitis(PSC).METHODS...AIM:To assess the role of IgM and IgG immunohistochemistry(IHC) in the evaluation of autoimmune liver conditions-autoimmune hepatitis(AIH),primary biliary cirrhosis(PBC),and primary sclerosing cholangitis(PSC).METHODS:Forty one biopsies from untreated patients diagnosed with autoimmune liver disease(AIH,n = 20;PBC,n = 13;PSC,n = 8) and fourteen biopsies of patients with chronic hepatitis C were selected.IgM and IgG-positive plasma cells were counted in each sample.RESULTS:A predominance of IgG-positive plasma cells was seen in AIH(90% of cases),PSC(75% of cases),and chronic hepatitis C(100% of cases),while IgMpositive plasma cells predominated in PBC(92.8% ofcases).The IgM /IgG ratio(< 1 or ≥ 1) accurately distinguished PBC from AIH in 90.9% of cases(sensitivity = 92.3%,specificity = 90%),and PBC from either AIH or PSC in 87.8% of cases(sensitivity = 92.3%,specificity = 85.7%).CONCLUSION:Plasmacytic infiltrates expressing predominantly IgM are characteristic of PBC,while other forms of liver disease analyzed in this study,including AIH,typically show an IgG-predominant plasma cell infiltrate.Our data indicate that IgM and IgG IHC may be a useful tool when PBC is a diagnostic consideration.展开更多
AIM: To determine cytomegalovirus (CMV) frequency in neonatal intrahepatic cholestasis by serology, histological revision (searching for cytomegalic cells), immunohistochemistry, and polymerase chain reaction (PCR), a...AIM: To determine cytomegalovirus (CMV) frequency in neonatal intrahepatic cholestasis by serology, histological revision (searching for cytomegalic cells), immunohistochemistry, and polymerase chain reaction (PCR), and to verify the relationships among these methods.METHODS: The study comprised 101 non-consecutive infants submitted for hepatic biopsy between March 1982 and December 2005. Serological results were obtained from the patient's f iles and the other methods were performed on paraffin-embedded liver samples from hepatic biopsies. The following statistical measures were calculated: frequency, sensibility, specif ic positive predictive value, negative predictive value, and accuracy.RESULTS: The frequencies of positive results were as follows: serology, 7/64 (11%); histological revision, 0/84; immunohistochemistry, 1/44 (2%), and PCR, 6/77 (8%). Only one patient had positive immunohistochemical fi ndings and a positive PCR. The following statistical measures were calculated between PCR and serology: sensitivity, 33.3%; specificity, 88.89%; positive predictive value, 28.57%; negative predictive value, 90.91%; and accuracy, 82.35%. CONCLUSION: The frequency of positive CMV varied among the tests. Serology presented the highest positive frequency. When compared to PCR, the sensitivity and positive predictive value of serology were low.展开更多
Renal cell carcinoma （RCC） compromises multiple types and has been emerging dramatically over the recent several decades. Advances and consensus have been achieved targeting common RCCs, such as clear cell carcinoma...Renal cell carcinoma （RCC） compromises multiple types and has been emerging dramatically over the recent several decades. Advances and consensus have been achieved targeting common RCCs, such as clear cell carcinoma, papillary RCC and chromophobe RCC. Nevertheless, little is known on the characteristics of several newly-identified RCCs, including clear cell （tubulo） papillary RCC, Xpl 1 translocation RCC, t（6;11） RCC, succinate dehydrogenase （SDH）-deficient RCC, acquired cystic disease- associated RCC, hereditary leiomyomatosis RCC syndrome-associated RCC, ALK translocation RCC, thyroid-like follicular RCC, tubulocystic RCC and hybrid oncocytic/chromophobe tumors （HOCT）. In current review, we will collect available literature of these newly-described RCCs, analyze their clinical pathologic characteristics, discuss their morphologic and immunohistologic features, and finally summarize their molecular and genetic evidences. We expect this review would be beneficial for the understanding of RCCs, and eventually promote clinical management strategies.展开更多
Blockade of immune checkpoints has recently emerged as a novel therapeutic strategy in various tumors. In particular,monoclonal antibodies targeting programmed cell death 1(PD-1) or its ligand(PD-L1) have been most st...Blockade of immune checkpoints has recently emerged as a novel therapeutic strategy in various tumors. In particular,monoclonal antibodies targeting programmed cell death 1(PD-1) or its ligand(PD-L1) have been most studied in lung cancer,and PD-1 inhibitors are now established agents in the management of non-small cell lung cancer(NSCLC). The reports on highprofile clinical trials have shown the association of PD-L1 expression by immunohistochemistry(IHC) with higher overall response rates to the PD-1/PD-L1 axis blockade suggesting that PD-L1 expression may serve as a predictive marker. Unfortunately,however, each PD-1 or PD-L1 inhibitor is coupled with a specific PD-L1 antibody, IHC protocol and scoring system for the biomarker assessment, making the head-to-head comparison of the studies difficult. Similarly, multiple clinical series that correlated PD-L1 expression with clinicopathologic and/or molecular variables and/or survival have reported conflicting results.The discrepancy could be explained by the differences in ethnicity and/or histologic types included in the studies, but it appears to be attributed in part to the differences in PD-L1 IHC methods. Thus, orchestrated efforts to standardize the PD-L1 IHC are warranted to establish the IHC as a predictive and/or prognostic biomarker in NSCLC.展开更多
Aim： To evaluate androgen receptor （AR） expression in clinically localized prostate cancer （PCa）. Methods： Specimens were studied from 232 patients who underwent radical prostatectomy for clinically localized pr...Aim： To evaluate androgen receptor （AR） expression in clinically localized prostate cancer （PCa）. Methods： Specimens were studied from 232 patients who underwent radical prostatectomy for clinically localized prostatic adenocarcinoma without neoadjuvant hormonal therapy or chemotherapy at our institution between November 2001 and June 2005. Immunohistochemical study was performed using an anti-human AR monoclonal antibody AR441. The mean AR density in the hot spots of different histological areas within the same sections were compared and the correlation of malignant epithelial AR density with clinicopathological parameters such as Gleason score, tumor, nodes and metastases （TNM） stage and pre-treatment prostate-specific antigen （PSA） value was assessed. Results： AR immunoreactivity was almost exclusively nuclear and was observed in tumor cells, non-neoplastic glandular epithelial cells and a proportion of peritumoral and interglandular stromal cells. Mean percentage of AR-positive epithelial cells was significantly higher in cancer tissues than that in normal prostate tissues （mean e SD, 90.0% ± 9.3% vs. 85.3% ±9.7%, P 〈 0.001）. The histological score yielded similar results. The percentage ofAR immunoreactive prostatic cancer nuclei and histological score were not correlated with existing parameters such as Gleason score, tumor, nodes and metastases stage and pre-treatment PSA value in this surgically treated cohort. Conclusion： The results of the present study suggest that there may be limited clinical use for determining AR expression （if evaluated in hot spots） in men with localized PCa.展开更多
Labrasol, as a non-ionic surfactant, can enhance the permeation and absorption of drugs, and is extensively used in topical, transdermal, and oral pharmaceutical preparations as an emulsifier and absorption enhancer. ...Labrasol, as a non-ionic surfactant, can enhance the permeation and absorption of drugs, and is extensively used in topical, transdermal, and oral pharmaceutical preparations as an emulsifier and absorption enhancer. Recent studies in our laboratory have indicated that labrasol has a strong absorption enhancing effect on different types of drugs in vitro and in vivo. This study was performed to further elucidate the action mechanism of labrasol on the corneal penetration. In this research, the fluorescein sodium, a marker of passive paracellular transport of tight junction, was selected as the model drug to assess the effect of labrasol on in vitro corneal permeability. To investigate the continuous and real-time influence of labrasol on the membrane permeability and integrity, the Ussing chamber system was applied to monitor the electrophysiological parameters. And, furthermore, we elucidated the effect of labrasol on excised cornea at the molecular level by application of RT-PCR, Western blot, and immunohistochemical staining. The results indicated that labrasol obviously enhance the transcorneal permeability of fluorescein sodium, and the enhancement was realized by interacting with and down-regulating the associated proteins, such as Factin, claudin-1 and β-catenin, which were contributed to cell-cell connections, respectively.展开更多
As a key contributor to memory storage, the synapse is one of the earliest affected neuronal components in Alzheimer＇s disease （AD）. Under physiological conditions, the synaptic con- nections between neurons underg...As a key contributor to memory storage, the synapse is one of the earliest affected neuronal components in Alzheimer＇s disease （AD）. Under physiological conditions, the synaptic con- nections between neurons undergo activity-dependent func- tional and morphological re-organisation. This dynamic, ＇plastic＇ neural ability critically depends on the structural integrity of the synapse. Thus, proteins that are implicated in preserving the organisation and dynamics of synaptic connections, including microtubules of the cytoskeleton and associated proteins, have attracted much focus for their involvement in the malfunction- ing AD synapse.展开更多
The accurate assessment ofa proto-oncogene, human epidermal growth factor receptor-2 gene （HER-2）, is extremely important for the therapy and prognosis of breast cancer. Currently, immunohistochemistry （IHC） is th...The accurate assessment ofa proto-oncogene, human epidermal growth factor receptor-2 gene （HER-2）, is extremely important for the therapy and prognosis of breast cancer. Currently, immunohistochemistry （IHC） is the method widely used for the detection of HER-2 protein. Fluorescence in situ hybridization （FISH） has been suggested to be a golden standard assay for HER-2 amplification. This study examined the expression and amplification of HER-2 in paraffin-embedded sections of breast cancer tissues, and compared the two methods on the measurement of HER-2 status. HER-2 gene and protein were determined in breast cancer samples from 52 Chinese women by FISH and IHC respectively. The findings indicated that the HER-2 gene amplification was found in 18 cases （34.6%） by FISH and the HER-2 protein over-expression （score 3＋） in 15 cases （28.8%） by IHC. hnmunohistochemically, 28.6% of the cases scored as 2＋ and 93.3% of the cases scored as 3＋ were HER-2-positive by FISH. There was a significant correlation between the HER-2 gene amplification and HER-2 protein over-expression in breast cancer （P〈0.005）. No correlation was noted between the HER-2 gene amplification and any of the clinicopathological parameters examined, including age, menopausal status, menarche age, tumor size, histological tumor type, histological grade, lymph node status, and the expression of ER and PR. It was concluded that the detection of HER-2 gene amplification in breast cancer by FISH is valuable and can compare with HER-2 protein detection by IHC.展开更多
Multiplexed immunohistochemistry/fluorescence(mIHC/IF)in combination with multispectral unmixing is a novel multitarget histopathological staining and imaging technique.By simultaneously revealing expression level and...Multiplexed immunohistochemistry/fluorescence(mIHC/IF)in combination with multispectral unmixing is a novel multitarget histopathological staining and imaging technique.By simultaneously revealing expression level and spatial information for up to eight biomarkers in situ,in addition to a nuclear stain within a single formalin-fixed paraffin-embedded(FFPE)tissue section,this technology can analyze the phenotype,abundance,morphology and intercellular relationship of cells while providing statistically significant results.In recent years,technical improvements have brought new insight into mIHC/IF and multispectral imaging approaches,which have been successfully applied in the field of cancer immunotherapy,specifically in regard to tumor microenvironment research,immunotherapy drug discovery,and prognostic and metastatic risk evaluation.This review highlights the principle,workflow,advantages and disadvantages of the technology,and discusses the latest applications of mIHC/IF-based imaging technology in the field of TME-related research and immunotherapy drug discovery.展开更多
The biological characteristics of the tumour are used to estimate prognosis and select appropriate systemic therapy for patients with(breast) cancer. The advent of molecular technology has incorporated new biomarkers ...The biological characteristics of the tumour are used to estimate prognosis and select appropriate systemic therapy for patients with(breast) cancer. The advent of molecular technology has incorporated new biomarkers along with immunohistochemical and serum biomarkers. Immunohistochemical markers are often used to guide treatment decisions, to classify breast cancer into subtypes that are biologically distinct and behave differently, and both as prognostic and predictive factors. Steroid hormone receptors, markers of tumour proliferation, and factors involved in angiogenesis and apoptosis are of scientific interest. In this review we will provide information on the immunohistochemical markers used in the management of breast cancer patients using available data from the literature. We consider the utility of established immunohistochemical markers, and discuss the challenges involved in integrating novel molecular markers into clinical practice.展开更多
BACKGROUND Gastric cancer(GC)is a highly heterogeneous disease,and the identification of molecular subtyping of gastric adenocarcinoma emerged as a promising option to define therapeutic strategies and prognostic subg...BACKGROUND Gastric cancer(GC)is a highly heterogeneous disease,and the identification of molecular subtyping of gastric adenocarcinoma emerged as a promising option to define therapeutic strategies and prognostic subgroups.However,the costs and technical complexity of molecular methodologies remains an obstacle to its adoption,and their clinical significance by other approaches needs further evidence.AIM To evaluate the clinicopathological characteristics and long-term survival of GC based on the subgroups of molecular classification by immunohistochemistry(IHC)and in situ hybridization(ISH).METHODS We retrospectively evaluated all patients who underwent D2-gastrectomy between 2009 and 2016 in a Western cohort of GC patients treated with curative intent.Microsatellite instability(MSI)status,E-cadherin,and p53 expression were analyzed by IHC,and Epstein-Barr virus(EBV)by ISH.Tissue microarrays were constructed for analysis.Clinicopathological characteristics and survival of GC were evaluated according to subtypes defined by The Cancer Genome Atlas(TCGA)Research Network Group and Asian Cancer Research Group(ACRG)classification systems.RESULTS A total of 287 GC patients were included.Based on IHC and ISH analysis,five profiles were defined as follows:E-cadherin aberrant(9.1%),MSI(20.9%),p53 aberrant(36.6%),EBV positivity(10.5%),and p53 normal(31%),which corresponded to tumors that showed no alteration in another profile.A flowchart according to the TCGA and ACRG classifications were used to define the subtypes,where clinical and pathological characteristics associated with GC subtypes were evidenced.Proximal location(P<0.001),total gastrectomy(P=0.001),and intense inflammatory infiltrate(P<0.001)were characteristics related to EBV subtype.MSI subtype was predominantly associated with advanced age(P=0.017)and the presence of comorbidities(P=0.011).While Laurén diffuse type(P<0.001)and advanced stage(P=0.029)were related to genomically stable(GS)subtype.GS tumors and microsatellite stable/epithelial to mesenchymal transition phenotype subtype had worse disease-free survival(DFS)and overall survival(OS)than other subtypes.Conversely,MSI subtype of GC had better survival in both classifications.Type of gastrectomy,pT and the TCGA subtypes were independent factors associated to DFS and OS.CONCLUSION The IHC/ISH analysis was able to distinguish immunophenotypic groups of GC with distinct characteristics and prognosis,resembling the subtypes of the molecular classifications.Accordingly,this method of classification may represent a viable option for use in a clinical setting.展开更多
The changes of carbamyl phosphate synthetase I(CPS 1)in diethylnitrosamine-(DEN)-inducedenzyme-altered liver cells were studied by means of immunohistochemical(PAP)and in situcDNA-mRNA hybridization methods.The experi...The changes of carbamyl phosphate synthetase I(CPS 1)in diethylnitrosamine-(DEN)-inducedenzyme-altered liver cells were studied by means of immunohistochemical(PAP)and in situcDNA-mRNA hybridization methods.The experimental rats were treated with DEN,2-acetylaminofluorene(2-AAF)and 2/3 hepatectomy according to Solt-Farber’s protocol andwere further promoted by oral daily administration of 0.05% phenobarbital in drinking water.The results showed that the average number of lesions showing abnormal expression of CPS1 was relatively constant over the course of the experiment(8 months),while the numberof normally expressing lesions gradually decreased.The former lesions were also largerin volume than the latter ones.We conclude that in DEN-initiated lesions the abnormallyexpressed CPS 1 lesions may grow continuously,thus leading to the formation of largernodules.We also suspect that some of these lesions have increased tendencies to developinto tumors.展开更多
Background The well-known ‘pyrotherapy’ of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play...Background The well-known ‘pyrotherapy’ of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play a pivotal role in neuroinfammatory processes. Maternal viral infection during pregnancy is associated with an increased risk for psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The present study was to quantify microglia activation in vivo in the mature offspring of rats exposed to polyriboinosinic–polyribocytidilicacid （Poly I：C） during pregnancy using ^11C-PK11195 positron emission tomography （PET） and immunohistochemistry.Objective The study aimed to quantify microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I：C exposed rats.Methods Offspring of Poly I：C-treated dams were the model group, offspring of saline-treated dams were the control group. Behavioural test for two groups was taken by spontaneous activity, prepulse inhibition （PPI） and latent inhibition （LI） test （including active avoidance conditioning task and passive avoidance conditioning task）. Randomly selected successful model rats were assessed by behavioural test in the model group and control group rats. 11C-PK11195 micro-PET/CT and immunohistochemistry were performed on the selected rats to measure microglia activation.Results The treatment group showed hyperlocomotion and defcits in PPI and LI compared with the control group. The treatment group also showed an increased 11C-PK11195 uptake ratio in the prefrontal cortex （t=-3.990, p=0.003） and hippocampus （t=-4.462, p=0.001）. The number of activated microglia cells was signifcantly higher in the treatment group than in the control group （hippocampus： t=8.204, p〈0.001; prefrontal： t=6.995, p〈0.001）. Within the treatment group, there were signifcant correlations between the behavioural parameters and the activation of microglia as measured by PET and immunohistochemistry.Conclusions The present study demonstrated microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I：C exposed rats. This study suggests that microglia activation may play a possible or potential role in the pathogenesis of schizophrenia.展开更多
Twelve quarters of six lactating cows were inoculated with Mycoplasma leachii strain GN407 through intramammary ductal infusion; another 12 quarters were inoculated with heat-inactivated M.leachii culture medium as ne...Twelve quarters of six lactating cows were inoculated with Mycoplasma leachii strain GN407 through intramammary ductal infusion; another 12 quarters were inoculated with heat-inactivated M.leachii culture medium as negative controls.Multidisciplinary procedures,including clinical assessment,etiology assessment,pathology and immunohistochemistry(IHC),were used to elucidate the pathogenicity of M.leachii in bovine mastitis.From post-inoculation days(PIDs) 3 to 9,12 inoculated quarters developed mild to severe clinical mastitis and mammary tissue histopathological changes,including inflammatory cell infiltration and architectural destruction of mammary gland ducts.The M.leachii antigen was also detected by IHC in the mammary gland epithelial cells of the inoculated quarters as a weak signal on PID 6 and as a strong signal on PID 9.The control quarters also developed mild mastitis and histopathological changes on PID 9,and M.leachii was also detected by IHC.Throughout the experimental period,the quarters of the negative control cow were clinically and pathologically normal,and the M.leachii antigen was not detected.In conclusion,direct histological and immunohistochemical evidence confirmed that M.leachii causes clinical bovine mastitis through histopathological lesions induced by invasion of the pathogen into mammary gland cells and through inflammatory cell infiltration.展开更多
One hundred and sixty-eight specimens of intestinal metaplasia(IM)with variousaccompanying lesions in gastric mucosa were studied with mucohistochemical and ABCimmunohistochemical staining,The quantitative analysis of...One hundred and sixty-eight specimens of intestinal metaplasia(IM)with variousaccompanying lesions in gastric mucosa were studied with mucohistochemical and ABCimmunohistochemical staining,The quantitative analysis of cell DNA was done withflowcytometry for 36 specimens.The results indicated that the incidence of type Ⅱb IM wassignificantly higher in the groups of dysplasia(34.6％)and mucosa adjacent to gastric cancer(GC)(51.7％)than in the chronic atrophic gastritis(CAG)group(16.0％)(P【0.01).The expres-sion rate of monoclonal antibody MG7 related antigen(MG7-Ag)in type Ⅱb IM(473％)wasalso significantly higher than those in type la(29.7％),Ib(26.1％)and Ⅱa IM(28.3％)(P【0.05).Expression rate of MG7-Ag,DNA aneuploid rate and percentage of S phase cell werestatistically higher in the type Ⅱb IM with dysphsia(62.5％,62.5％ and 143±32)than in typeⅡb 1M without dysplasia(47.3％,12.5％and12.7±2.9)(P【0.05 and P【0.01).These findingssuppor the supposed progressive process:CAG→type Ⅱb IM→dysplasia→GC,andtype Ⅱb IM with dysplasia is closely associated with GC.展开更多
Background: Brucellosis in male goats is characterized by arthritis, orchitis and epididymitis, which may induce infertility. Nevertheless, these lesions were categorized as chronic while acute lesions had not been de...Background: Brucellosis in male goats is characterized by arthritis, orchitis and epididymitis, which may induce infertility. Nevertheless, these lesions were categorized as chronic while acute lesions had not been described. This study investigates the histopathological and immuno histochemistry reactions in organs of bucks acutely infected by Brucella melitensis. Results: Only testis and prepuce of acutely infected bucks showed significantly severe histological lesions. Other internal organs had mild to moderate lesions. However, positive immunohistochemistry stainings were observed in organs except the bulbourethral gland. There was a significant positive correlation between the distribution of B. melitensis and IHC intensity but no significant correlation between the IHC intensity and histopathology lesions. Conclusion: The results indicate that acute brucellosis did not lead to clinical presentation, although B. melitensis was well distributed in various organs of bucks.展开更多
基金Supported by Seoul National University Bundang Hospital Research Fund,No.06-2021-0140National Research Foundation of Korea,No.RS-2024-00335454.
文摘BACKGROUND Among all solid tumors,pancreatic ductal adenocarcinoma(PDAC)is charac-terized by markedly poor survival outcomes,reflecting its high lethality,primarily as a result of late-stage diagnosis and limited treatment options.Pancreatic adenocarcinoma upregulated factor(PAUF)displays elevated expression in PDAC compared to non-neoplastic pancreatic samples and is involved in promoting tumor development.However,its exact diagnostic and prognostic significance remains unclear.This study aimed to assess the clinical relevance of PAUF expression in PDAC.We hypothesized that higher PAUF expression is associated with more aggressive clinicopathological features and poorer patient outcomes.AIM To investigate the expression of PAUF in PDAC and its value as a diagnostic and prognostic biomarker.METHODS PAUF expression levels were assessed using immunohistochemistry in tumor tissues from 93 patients with PDAC.Staining intensity and the proportion of tumor cells showing PAUF positivity were assessed to categorize patients into low and high PAUF expression groups.Associations between PAUF expression and clinicopathological characteristics or survival outcomes were analyzed.Public datasets(The Cancer Genome Atlas,Genotype-Tissue Expression,and Clinical Proteomic Tumor Analysis Consortium)were employed to validate differences in PAUF expression in PDAC at mRNA and protein levels.RESULTS PAUF expression was observed in 82.8%of samples,primarily localized within the cytoplasm of tumor cells.High PAUF expression showed a significant correlation with metastasis to lymph nodes(78.4%,P=0.0019),indicating a strong association with advanced disease.Public datasets confirmed elevated PAUF levels at both transcript and protein levels in PDAC relative to normal tissue.Kaplan-Meier estimates indicated that higher PAUF levels were linked with shorter overall survival(18.4 months vs 32.7 months,P=0.032).Multivariate Cox regression confirmed high PAUF expression as a prognostically significant variable contributing to poor clinical outcomes[hazard ratio(HR)=2.05;P=0.009].Poor tumor differentiation(HR=2.47;P=0.004)and lack of adjuvant therapy(HR=0.39;P=0.001)were also independently associated with unfavorable outcomes.CONCLUSION PAUF is a promising biomarker for tumor progression and prognosis in PDAC,with potential clinical utility in early diagnosis and the development of targeted therapies.
文摘This study investigates the variability in cancer diagnosis across different tissues and organs, with a focus on the role of diagnostic methods such as Hematoxylin and Eosin (H&E) staining and immunohistochemistry (IHC). The predominance of female breast cancer (30%) aligns with global trends, underscoring the need for robust diagnostic protocols, particularly in developing regions. Other prevalent cancers, including skin, stomach, and cervix uteri, reflect a mix of environmental, genetic, and infectious factors. The underrepresentation of gallbladder and thyroid cancers (<1%) suggests potential underdiagnosis or lower prevalence. Age distribution data indicate peak cancer incidence in individuals aged 31 - 45 years, with gender-specific cancers like breast and cervical cancer predominantly affecting females (63.4%). The analysis also highlights significant diagnostic gaps, as 61.2% of cases did not undergo IHC testing due to resource constraints, leading to potential biases in cancer prevalence and diagnostic accuracy. The study emphasizes the complementary role of IHC in confirming ambiguous H&E findings, with strong alignment observed when both methods were used. However, the absence of IHC in many cases limits the robustness of conclusions, suggesting the need for increased access to IHC testing. The findings advocate for integrating IHC into routine diagnostics, expanding diagnostic capabilities, and improving sample sizes to ensure more reliable and comprehensive cancer data.
基金Supported by Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project,No.Z-A20220521Guangxi Higher Education Undergraduate Teaching Reform Project,No.2022JGA147The National College Students’Innovation and Entrepreneurship Training Program,No.202310598042.
文摘BACKGROUND Although thymopoietin(TMPO)has been elucidated to be overexpressed in cancers,its underlying mechanisms are not yet fully understood.AIM To investigate the expression and clinical significance of TMPO in papillary thyroid carcinoma(PTC).METHODS Databases such as Gene Expression Omnibus,The Cancer Genome Atlas Proand summary receiver operating characteristic curves were plotted to evaluate diagnostic performance.A Gene Set Enrichment Analysis enrichment analysis was conducted to identify TMPO-related signaling pathways.A protein interaction network was constructed to identify hub genes.The impact of TMPO on PTC cell proliferation and the effects of its knockout were analyzed using clustered regularly interspaced short palindromic repeats(CRISPR)knockout screening and the Cancer Cell Line Encyclopedia database.RESULTS The TMPO protein was significantly overexpressed in PTC tissues,primarily localized in the cytoplasm and nuclear membrane.The mRNA level analysis showed mild overexpression of TMPO in PTC tissues,with a certain discriminatory value(area under the curve=0.66).TMPO may promote cancer through involvement in cell adhesion,focal adhesion,leukocyte migration,and multiple cancer-related signaling pathways.Additionally,CRISPR gene knockout experiments confirmed that TMPO knockout significantly inhibited the proliferation of PTC cell lines,indicating its important role in tumor growth.CONCLUSION TMPO is overexpressed in PTC and may serve as a therapeutic target and molecular biomarker for PTC.
基金Supported by the Scientific and Technological Foundation of the Jiangxi Provincial Department of Science and Technology
文摘AIM： To study the endoscopic, pathological and immunoo histochemical features of esophageal mesenchymal tumors. METHODS： Twenty-nine patients diagnosed as esophageal rnysenchymal tumors by electronic endoscopy and endoscopic ultrasound （EUS） were observed under light microscopes, and all tissues were stained by the immunohistochemical method. The expression of CD117, CD34, SMA and desmin were measured by staining intensity of cells and positive cell ratios. RESULTS： Endoscopically, esophageal gastrointestinal stromal tumors （GISTs） and leiomyomas （LMs） had similar appearances, showing submucosal protuberant lesions. They all showed low echo images originated from the muscularis propria or muscularis mucosa on EUS. Endoscopy and EUS could not exactly differentiate esophageal GISTs from LMs. Microscopically, there were two kinds of cells： spindle cell type and epitheloid cell type in esophageal GISTs. Leiomyomas and leiomyosarcornas were only of spindle cell type. One malignancy was found in five cases of esophageal GISTs, and one malignancy in 24 cases of leiomyomas and leiomyosarcomas. Using Fisher＇s exact method, the differences of malignant lesion proportion were not significant between esophageal LMs and GISTs, 1/5 vs 1/24 （P 〉 0.05）. All cases of esophageal GISTs were positive for CD117, and 3 cases were also positive for CD34. The 24 cases of leiomyomas and leiomyosarcomas were all negative for CD117 and CD34. The differences of positive rates of CD117 and CD34 were significant between esophageal GISTs and LMs, 5/5 vs 0/24, 3/5 vs 0/24 （P 〈 0.005）. All leiomyomas and leiomyosarcomas were positive for SMA, and desmin. Among 5 cases of esophageal GISTs, 2 cases were SMA positive, and 1 case was desmin positive. The differences in positive rates and expression intensity of SMA and desmin were significant between esophageal LMs and GISTs, 24/24 vs 2/5, 24/24 vs 115 （P 〈 0.005）. CONCLUSION： The most common esophageal mesenchymal tumors are leiomyomas, and esophageal GISTs are less common. Most of esophageal LMs and GISTs are benign. Endoscopy and EUS are the effective methods to diagnose esophageal mesenchymal tumors and they can provide useful information for the treatment of these tumors. However, they cannot exactly differentiate esophageal GISTs from LMs. Pathological, especially immunohistochemical features are useful to differentiate GISTs from leiomyomas.
基金Supported by Vanderbilt University Medical Center’s Digestive Disease Research Center,NIH Grant P30DK058404
文摘AIM:To assess the role of IgM and IgG immunohistochemistry(IHC) in the evaluation of autoimmune liver conditions-autoimmune hepatitis(AIH),primary biliary cirrhosis(PBC),and primary sclerosing cholangitis(PSC).METHODS:Forty one biopsies from untreated patients diagnosed with autoimmune liver disease(AIH,n = 20;PBC,n = 13;PSC,n = 8) and fourteen biopsies of patients with chronic hepatitis C were selected.IgM and IgG-positive plasma cells were counted in each sample.RESULTS:A predominance of IgG-positive plasma cells was seen in AIH(90% of cases),PSC(75% of cases),and chronic hepatitis C(100% of cases),while IgMpositive plasma cells predominated in PBC(92.8% ofcases).The IgM /IgG ratio(< 1 or ≥ 1) accurately distinguished PBC from AIH in 90.9% of cases(sensitivity = 92.3%,specificity = 90%),and PBC from either AIH or PSC in 87.8% of cases(sensitivity = 92.3%,specificity = 85.7%).CONCLUSION:Plasmacytic infiltrates expressing predominantly IgM are characteristic of PBC,while other forms of liver disease analyzed in this study,including AIH,typically show an IgG-predominant plasma cell infiltrate.Our data indicate that IgM and IgG IHC may be a useful tool when PBC is a diagnostic consideration.
基金Supported by The State of So Paulo Research Foundation (Fapesp)and the Coordination for Higher Level Graduates Improvement (Capes)
文摘AIM: To determine cytomegalovirus (CMV) frequency in neonatal intrahepatic cholestasis by serology, histological revision (searching for cytomegalic cells), immunohistochemistry, and polymerase chain reaction (PCR), and to verify the relationships among these methods.METHODS: The study comprised 101 non-consecutive infants submitted for hepatic biopsy between March 1982 and December 2005. Serological results were obtained from the patient's f iles and the other methods were performed on paraffin-embedded liver samples from hepatic biopsies. The following statistical measures were calculated: frequency, sensibility, specif ic positive predictive value, negative predictive value, and accuracy.RESULTS: The frequencies of positive results were as follows: serology, 7/64 (11%); histological revision, 0/84; immunohistochemistry, 1/44 (2%), and PCR, 6/77 (8%). Only one patient had positive immunohistochemical fi ndings and a positive PCR. The following statistical measures were calculated between PCR and serology: sensitivity, 33.3%; specificity, 88.89%; positive predictive value, 28.57%; negative predictive value, 90.91%; and accuracy, 82.35%. CONCLUSION: The frequency of positive CMV varied among the tests. Serology presented the highest positive frequency. When compared to PCR, the sensitivity and positive predictive value of serology were low.
基金Supported by National Natural Science Foundation of China(81472391,81101933,Q Rao)National Natural Science Foundation of China(81372743XJ Zhou)
文摘Renal cell carcinoma （RCC） compromises multiple types and has been emerging dramatically over the recent several decades. Advances and consensus have been achieved targeting common RCCs, such as clear cell carcinoma, papillary RCC and chromophobe RCC. Nevertheless, little is known on the characteristics of several newly-identified RCCs, including clear cell （tubulo） papillary RCC, Xpl 1 translocation RCC, t（6;11） RCC, succinate dehydrogenase （SDH）-deficient RCC, acquired cystic disease- associated RCC, hereditary leiomyomatosis RCC syndrome-associated RCC, ALK translocation RCC, thyroid-like follicular RCC, tubulocystic RCC and hybrid oncocytic/chromophobe tumors （HOCT）. In current review, we will collect available literature of these newly-described RCCs, analyze their clinical pathologic characteristics, discuss their morphologic and immunohistologic features, and finally summarize their molecular and genetic evidences. We expect this review would be beneficial for the understanding of RCCs, and eventually promote clinical management strategies.
基金supported by a Stand Up To Cancer-American Cancer Society Dream Team Translation Research Grant
文摘Blockade of immune checkpoints has recently emerged as a novel therapeutic strategy in various tumors. In particular,monoclonal antibodies targeting programmed cell death 1(PD-1) or its ligand(PD-L1) have been most studied in lung cancer,and PD-1 inhibitors are now established agents in the management of non-small cell lung cancer(NSCLC). The reports on highprofile clinical trials have shown the association of PD-L1 expression by immunohistochemistry(IHC) with higher overall response rates to the PD-1/PD-L1 axis blockade suggesting that PD-L1 expression may serve as a predictive marker. Unfortunately,however, each PD-1 or PD-L1 inhibitor is coupled with a specific PD-L1 antibody, IHC protocol and scoring system for the biomarker assessment, making the head-to-head comparison of the studies difficult. Similarly, multiple clinical series that correlated PD-L1 expression with clinicopathologic and/or molecular variables and/or survival have reported conflicting results.The discrepancy could be explained by the differences in ethnicity and/or histologic types included in the studies, but it appears to be attributed in part to the differences in PD-L1 IHC methods. Thus, orchestrated efforts to standardize the PD-L1 IHC are warranted to establish the IHC as a predictive and/or prognostic biomarker in NSCLC.
文摘Aim： To evaluate androgen receptor （AR） expression in clinically localized prostate cancer （PCa）. Methods： Specimens were studied from 232 patients who underwent radical prostatectomy for clinically localized prostatic adenocarcinoma without neoadjuvant hormonal therapy or chemotherapy at our institution between November 2001 and June 2005. Immunohistochemical study was performed using an anti-human AR monoclonal antibody AR441. The mean AR density in the hot spots of different histological areas within the same sections were compared and the correlation of malignant epithelial AR density with clinicopathological parameters such as Gleason score, tumor, nodes and metastases （TNM） stage and pre-treatment prostate-specific antigen （PSA） value was assessed. Results： AR immunoreactivity was almost exclusively nuclear and was observed in tumor cells, non-neoplastic glandular epithelial cells and a proportion of peritumoral and interglandular stromal cells. Mean percentage of AR-positive epithelial cells was significantly higher in cancer tissues than that in normal prostate tissues （mean e SD, 90.0% ± 9.3% vs. 85.3% ±9.7%, P 〈 0.001）. The histological score yielded similar results. The percentage ofAR immunoreactive prostatic cancer nuclei and histological score were not correlated with existing parameters such as Gleason score, tumor, nodes and metastases stage and pre-treatment PSA value in this surgically treated cohort. Conclusion： The results of the present study suggest that there may be limited clinical use for determining AR expression （if evaluated in hot spots） in men with localized PCa.
文摘Labrasol, as a non-ionic surfactant, can enhance the permeation and absorption of drugs, and is extensively used in topical, transdermal, and oral pharmaceutical preparations as an emulsifier and absorption enhancer. Recent studies in our laboratory have indicated that labrasol has a strong absorption enhancing effect on different types of drugs in vitro and in vivo. This study was performed to further elucidate the action mechanism of labrasol on the corneal penetration. In this research, the fluorescein sodium, a marker of passive paracellular transport of tight junction, was selected as the model drug to assess the effect of labrasol on in vitro corneal permeability. To investigate the continuous and real-time influence of labrasol on the membrane permeability and integrity, the Ussing chamber system was applied to monitor the electrophysiological parameters. And, furthermore, we elucidated the effect of labrasol on excised cornea at the molecular level by application of RT-PCR, Western blot, and immunohistochemical staining. The results indicated that labrasol obviously enhance the transcorneal permeability of fluorescein sodium, and the enhancement was realized by interacting with and down-regulating the associated proteins, such as Factin, claudin-1 and β-catenin, which were contributed to cell-cell connections, respectively.
基金supported by grant SDU2020 to Prof.Bente Finsen and Prof.Martin R.Larsen(COPING AD–Collaborative Project on the Interaction between Neurons and Glia in Alzheimer’s Disease)
文摘As a key contributor to memory storage, the synapse is one of the earliest affected neuronal components in Alzheimer＇s disease （AD）. Under physiological conditions, the synaptic con- nections between neurons undergo activity-dependent func- tional and morphological re-organisation. This dynamic, ＇plastic＇ neural ability critically depends on the structural integrity of the synapse. Thus, proteins that are implicated in preserving the organisation and dynamics of synaptic connections, including microtubules of the cytoskeleton and associated proteins, have attracted much focus for their involvement in the malfunction- ing AD synapse.
基金supported by a grant from Ministry of Public Health of China (No. WKJ2007-3-001)
文摘The accurate assessment ofa proto-oncogene, human epidermal growth factor receptor-2 gene （HER-2）, is extremely important for the therapy and prognosis of breast cancer. Currently, immunohistochemistry （IHC） is the method widely used for the detection of HER-2 protein. Fluorescence in situ hybridization （FISH） has been suggested to be a golden standard assay for HER-2 amplification. This study examined the expression and amplification of HER-2 in paraffin-embedded sections of breast cancer tissues, and compared the two methods on the measurement of HER-2 status. HER-2 gene and protein were determined in breast cancer samples from 52 Chinese women by FISH and IHC respectively. The findings indicated that the HER-2 gene amplification was found in 18 cases （34.6%） by FISH and the HER-2 protein over-expression （score 3＋） in 15 cases （28.8%） by IHC. hnmunohistochemically, 28.6% of the cases scored as 2＋ and 93.3% of the cases scored as 3＋ were HER-2-positive by FISH. There was a significant correlation between the HER-2 gene amplification and HER-2 protein over-expression in breast cancer （P〈0.005）. No correlation was noted between the HER-2 gene amplification and any of the clinicopathological parameters examined, including age, menopausal status, menarche age, tumor size, histological tumor type, histological grade, lymph node status, and the expression of ER and PR. It was concluded that the detection of HER-2 gene amplification in breast cancer by FISH is valuable and can compare with HER-2 protein detection by IHC.
基金supported by State Key Laboratory of Natural and Biomimetic Drugs,Peking University。
文摘Multiplexed immunohistochemistry/fluorescence(mIHC/IF)in combination with multispectral unmixing is a novel multitarget histopathological staining and imaging technique.By simultaneously revealing expression level and spatial information for up to eight biomarkers in situ,in addition to a nuclear stain within a single formalin-fixed paraffin-embedded(FFPE)tissue section,this technology can analyze the phenotype,abundance,morphology and intercellular relationship of cells while providing statistically significant results.In recent years,technical improvements have brought new insight into mIHC/IF and multispectral imaging approaches,which have been successfully applied in the field of cancer immunotherapy,specifically in regard to tumor microenvironment research,immunotherapy drug discovery,and prognostic and metastatic risk evaluation.This review highlights the principle,workflow,advantages and disadvantages of the technology,and discusses the latest applications of mIHC/IF-based imaging technology in the field of TME-related research and immunotherapy drug discovery.
文摘The biological characteristics of the tumour are used to estimate prognosis and select appropriate systemic therapy for patients with(breast) cancer. The advent of molecular technology has incorporated new biomarkers along with immunohistochemical and serum biomarkers. Immunohistochemical markers are often used to guide treatment decisions, to classify breast cancer into subtypes that are biologically distinct and behave differently, and both as prognostic and predictive factors. Steroid hormone receptors, markers of tumour proliferation, and factors involved in angiogenesis and apoptosis are of scientific interest. In this review we will provide information on the immunohistochemical markers used in the management of breast cancer patients using available data from the literature. We consider the utility of established immunohistochemical markers, and discuss the challenges involved in integrating novel molecular markers into clinical practice.
基金Supported by Fundação de Amparo à Pesquisa do Estado de São Paulo(FAPESP agency),No.2016/25524-0.
文摘BACKGROUND Gastric cancer(GC)is a highly heterogeneous disease,and the identification of molecular subtyping of gastric adenocarcinoma emerged as a promising option to define therapeutic strategies and prognostic subgroups.However,the costs and technical complexity of molecular methodologies remains an obstacle to its adoption,and their clinical significance by other approaches needs further evidence.AIM To evaluate the clinicopathological characteristics and long-term survival of GC based on the subgroups of molecular classification by immunohistochemistry(IHC)and in situ hybridization(ISH).METHODS We retrospectively evaluated all patients who underwent D2-gastrectomy between 2009 and 2016 in a Western cohort of GC patients treated with curative intent.Microsatellite instability(MSI)status,E-cadherin,and p53 expression were analyzed by IHC,and Epstein-Barr virus(EBV)by ISH.Tissue microarrays were constructed for analysis.Clinicopathological characteristics and survival of GC were evaluated according to subtypes defined by The Cancer Genome Atlas(TCGA)Research Network Group and Asian Cancer Research Group(ACRG)classification systems.RESULTS A total of 287 GC patients were included.Based on IHC and ISH analysis,five profiles were defined as follows:E-cadherin aberrant(9.1%),MSI(20.9%),p53 aberrant(36.6%),EBV positivity(10.5%),and p53 normal(31%),which corresponded to tumors that showed no alteration in another profile.A flowchart according to the TCGA and ACRG classifications were used to define the subtypes,where clinical and pathological characteristics associated with GC subtypes were evidenced.Proximal location(P<0.001),total gastrectomy(P=0.001),and intense inflammatory infiltrate(P<0.001)were characteristics related to EBV subtype.MSI subtype was predominantly associated with advanced age(P=0.017)and the presence of comorbidities(P=0.011).While Laurén diffuse type(P<0.001)and advanced stage(P=0.029)were related to genomically stable(GS)subtype.GS tumors and microsatellite stable/epithelial to mesenchymal transition phenotype subtype had worse disease-free survival(DFS)and overall survival(OS)than other subtypes.Conversely,MSI subtype of GC had better survival in both classifications.Type of gastrectomy,pT and the TCGA subtypes were independent factors associated to DFS and OS.CONCLUSION The IHC/ISH analysis was able to distinguish immunophenotypic groups of GC with distinct characteristics and prognosis,resembling the subtypes of the molecular classifications.Accordingly,this method of classification may represent a viable option for use in a clinical setting.
文摘The changes of carbamyl phosphate synthetase I(CPS 1)in diethylnitrosamine-(DEN)-inducedenzyme-altered liver cells were studied by means of immunohistochemical(PAP)and in situcDNA-mRNA hybridization methods.The experimental rats were treated with DEN,2-acetylaminofluorene(2-AAF)and 2/3 hepatectomy according to Solt-Farber’s protocol andwere further promoted by oral daily administration of 0.05% phenobarbital in drinking water.The results showed that the average number of lesions showing abnormal expression of CPS1 was relatively constant over the course of the experiment(8 months),while the numberof normally expressing lesions gradually decreased.The former lesions were also largerin volume than the latter ones.We conclude that in DEN-initiated lesions the abnormallyexpressed CPS 1 lesions may grow continuously,thus leading to the formation of largernodules.We also suspect that some of these lesions have increased tendencies to developinto tumors.
基金provided by the National Natural Science Foundation of China(No 81571318 to XQSNo 81371472 to LXL+5 种基金No 81401110 to XL)the Science and Technology Planning Project of Health and Family Planning Commission(No 201501015 to XQS)the International Science and Technology Cooperation Program of Henan(No 162102410061 to XQS)the Henan Province Union Fund Project(162300410275)the Zhengzhou University doctor team projectthe Youth Fund of the First Affiliated Hospital of Zhengzhou University(to XL and LJP)
文摘Background The well-known ‘pyrotherapy’ of Julius Wagner-Jauregg might be the beginning of the study on the immunological concepts of schizophrenia. As the primary immune effector cells in the brain, microglia play a pivotal role in neuroinfammatory processes. Maternal viral infection during pregnancy is associated with an increased risk for psychiatric disorders with presumed neurodevelopmental origin, including autism spectrum disorders and schizophrenia. The present study was to quantify microglia activation in vivo in the mature offspring of rats exposed to polyriboinosinic–polyribocytidilicacid （Poly I：C） during pregnancy using ^11C-PK11195 positron emission tomography （PET） and immunohistochemistry.Objective The study aimed to quantify microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I：C exposed rats.Methods Offspring of Poly I：C-treated dams were the model group, offspring of saline-treated dams were the control group. Behavioural test for two groups was taken by spontaneous activity, prepulse inhibition （PPI） and latent inhibition （LI） test （including active avoidance conditioning task and passive avoidance conditioning task）. Randomly selected successful model rats were assessed by behavioural test in the model group and control group rats. 11C-PK11195 micro-PET/CT and immunohistochemistry were performed on the selected rats to measure microglia activation.Results The treatment group showed hyperlocomotion and defcits in PPI and LI compared with the control group. The treatment group also showed an increased 11C-PK11195 uptake ratio in the prefrontal cortex （t=-3.990, p=0.003） and hippocampus （t=-4.462, p=0.001）. The number of activated microglia cells was signifcantly higher in the treatment group than in the control group （hippocampus： t=8.204, p〈0.001; prefrontal： t=6.995, p〈0.001）. Within the treatment group, there were signifcant correlations between the behavioural parameters and the activation of microglia as measured by PET and immunohistochemistry.Conclusions The present study demonstrated microglia activation in vivo in the prefrontal cortex and hippocampus in mature offspring of prenatal Poly I：C exposed rats. This study suggests that microglia activation may play a possible or potential role in the pathogenesis of schizophrenia.
基金funded by the Natural Science Fund Project of Heilongjiang Province of China (C201348)the grants from the Central Public-interest Scientific Institution Basal Research Fund,China (1610302016001)the National Science and Technology Program Topics of China (2012BAD12B03-3)
文摘Twelve quarters of six lactating cows were inoculated with Mycoplasma leachii strain GN407 through intramammary ductal infusion; another 12 quarters were inoculated with heat-inactivated M.leachii culture medium as negative controls.Multidisciplinary procedures,including clinical assessment,etiology assessment,pathology and immunohistochemistry(IHC),were used to elucidate the pathogenicity of M.leachii in bovine mastitis.From post-inoculation days(PIDs) 3 to 9,12 inoculated quarters developed mild to severe clinical mastitis and mammary tissue histopathological changes,including inflammatory cell infiltration and architectural destruction of mammary gland ducts.The M.leachii antigen was also detected by IHC in the mammary gland epithelial cells of the inoculated quarters as a weak signal on PID 6 and as a strong signal on PID 9.The control quarters also developed mild mastitis and histopathological changes on PID 9,and M.leachii was also detected by IHC.Throughout the experimental period,the quarters of the negative control cow were clinically and pathologically normal,and the M.leachii antigen was not detected.In conclusion,direct histological and immunohistochemical evidence confirmed that M.leachii causes clinical bovine mastitis through histopathological lesions induced by invasion of the pathogen into mammary gland cells and through inflammatory cell infiltration.
文摘One hundred and sixty-eight specimens of intestinal metaplasia(IM)with variousaccompanying lesions in gastric mucosa were studied with mucohistochemical and ABCimmunohistochemical staining,The quantitative analysis of cell DNA was done withflowcytometry for 36 specimens.The results indicated that the incidence of type Ⅱb IM wassignificantly higher in the groups of dysplasia(34.6％)and mucosa adjacent to gastric cancer(GC)(51.7％)than in the chronic atrophic gastritis(CAG)group(16.0％)(P【0.01).The expres-sion rate of monoclonal antibody MG7 related antigen(MG7-Ag)in type Ⅱb IM(473％)wasalso significantly higher than those in type la(29.7％),Ib(26.1％)and Ⅱa IM(28.3％)(P【0.05).Expression rate of MG7-Ag,DNA aneuploid rate and percentage of S phase cell werestatistically higher in the type Ⅱb IM with dysphsia(62.5％,62.5％ and 143±32)than in typeⅡb 1M without dysplasia(47.3％,12.5％and12.7±2.9)(P【0.05 and P【0.01).These findingssuppor the supposed progressive process:CAG→type Ⅱb IM→dysplasia→GC,andtype Ⅱb IM with dysplasia is closely associated with GC.
文摘Background: Brucellosis in male goats is characterized by arthritis, orchitis and epididymitis, which may induce infertility. Nevertheless, these lesions were categorized as chronic while acute lesions had not been described. This study investigates the histopathological and immuno histochemistry reactions in organs of bucks acutely infected by Brucella melitensis. Results: Only testis and prepuce of acutely infected bucks showed significantly severe histological lesions. Other internal organs had mild to moderate lesions. However, positive immunohistochemistry stainings were observed in organs except the bulbourethral gland. There was a significant positive correlation between the distribution of B. melitensis and IHC intensity but no significant correlation between the IHC intensity and histopathology lesions. Conclusion: The results indicate that acute brucellosis did not lead to clinical presentation, although B. melitensis was well distributed in various organs of bucks.
