Expression of KAI1/CD82 and MRP-1/CD9 in Transitional Cell Carcinoma of Bladder

The expression of KAI1/CD82 and MRP-1/CD9 in transitional cell carcinoma of bladder （TCCB） and its clinical significance were investigated. Immunohistochemistry was used to detect KAI1/CD82 and MRP-1/CD9 protein expression in 52 TCCB specimens. Correlation between the expression of KAI1/CD82 and MRP-1/CD9 to clinicopathologic factors was statistically analyzed. The results showed that the positive rate of KAI1/CD82 and MRP-1/CD9 in TCCB was 50% and 61.5%, respectively. The MRP-1/CD9 and KAI1/CD82 expression was significantly associated with grade of TCCB （P〈0.05）, but no correlation was found between MRP-1/CD9 or KAI1/CD82 expression and clinical stage of TCCB （P〉0.05）. The expression level of MRP-1/CD9 and KAI1/CD82 in recurrent TCCB samples was lower than that in non-recurrent samples （P〈0.05）. Meanwhile, the correlation between the KAI1/CD82 expression and MRP-1/CD9 expression was statistically significant （r=0.316, P〈0.05）. It was concluded that KAI1/CD82 and MRP-1/CD9 expression may be important prognostic indicators and potentially useful for assessing the biological behavior of TCCB.

MTHFR C677T polymorphisms are associated with aberrant methylation of the IGF-2 gene in transitional cell carcinoma of the bladder

The purpose of this study was to determine the relationship between methylation status of the insulin-like growth factor 2 （IGF-2） gene and methylenetetrahydrofolate reductase （MTHFR） C677T gene polymorphisms in bladder transitional cell carcinoma tissues in a Chinese population. The polymorphisms of the folate metabolism enzyme gene MTHFR were studied by restrictive fragment length polymorphism （RFLP）, PCR-based methods of DNA methylation analysis were used to detect the CpG island methylation status of the IGF-2 gene. The association between the methylation status of the IGF-2 gene and clinical characteristics, as well as MTHFR C677T polymorphisms, was analyzed. Aberrant hypomethylation of the IGF-2 gene was found in 68.3% bladder cancer tissues and 12.4% normal bladder tissues, respectively, while hypomethylation was not detected in almost all normal bladder tissues. The hypomethylation rate of the IGF-2 gene in cancer tissues was significantly higher in patients with lymph node metastasis than in those without lymph node metastasis （46.3% vs 17.2%, P = 0.018）. No association was found between aberrant DNA methylation and selected factors including sex, age, tobacco smoking, alcohol consumption and green tea consumption. After adjusting for potential confounding variables the variant allele of MTHFR C677T was found to be associated with hypomethylation of the IGF-2 gene. Compared with wildtype CC, the odds ratio was 4.33 （95% CI=1.06-10.59） for CT and 4,95 （95% CI=1.18-12.74） for TT. MTHFR 677 CC and CT genotypes might be one of the reasons that cause abnormal hypomethylation of the IGF-2 gene, and the aberrant CpG island hypomethylation of the IGF-2 gene may contribute to the genesis and progression of bladder transitional cell carcinoma.

RECURRENCE RISK FACTORS IN PATIENTS WITH TRANSITIONAL CELL CARCINOMA OF BLADDER

Objective： To study recurrence factors and set up a model to evaluate the prognosis of patients with bladder cancer. Methods： An analysis on recurrence-related factors was made by Cox＇s proportional hazards model analysis and logistic multiple linear regression model analysis in 212 patients with transitional cell carcinoma treated surgically from 1995-2001. These factors included clinical and pathologic figures. Results： The most important factor is metastasis to the regional lymph nodes, the Hazards ratio is 6.6 （P=0.0004）, followed by multiple tumors （Hr=2.255, P〈0.0001）, tumor in trigone and bladder neck （Hr=2.053, P〈0.0001）, stage （Hr=2.057, P〈0.0001）, grade （Hr=1.569, P=0.0081）, intravesical chemotherapeutic instillations （Hr-0.559, P=0.0011） and hematuria （Hr=0.762, P=0.0076）. A predicting equation was established, and the predicting values were calculated according to the individual features of patients. The predicting and actual values were compared, and the sensitivity, specificity and overall concordance were 83.5%, 67.6% and 80.1% respectively. Conelusion：The evaluation of prognosis could be made quite accurately based on these factors.

Cloning of Human Uroplakin Ⅱ Gene from Chinese Transitional Cell Carcinoma of Bladder and Construction of Its Eukaryotic Expression Vector

Summary: To clone Uroplakin Ⅱ gene from Chinese transitional cell carcinoma (TCC) of bladder and construct its eukaryotic expression vector, the molecular cloning method was used to extract total RNA from a GⅢ/ T 3N 0M 0 tissue sample of the bladder TCC patients. The primers were designed by Primer 5.0 software. Full length cDNA of Uroplakin Ⅱ gene was amplified by reverse transcription polymerase chain reaction (RT-PCR), assayed by nucleic acid sequencing and then inserted between XbaⅠ and HindⅢ restrictive sites of eukaryotic expression vector pcDNA3.0. The recombinant was assayed by restricted enzyme digestion. Under the induction of Lipofectamine 2000, the recombinant was transfected into Uroplakin Ⅱ negative bladder cancer cell line EJ. Cellular expression levels of Uroplakin Ⅱ were detected by RT-PCR. The nucleic acid sequencing results indicated that Chinese Uroplakin Ⅱ cDNA (555 bp) was successfully cloned. The BLAST analysis demonstrated that the cloned sequence is 100 % homologous with sequences reported overseas. The GenBank accession number AY455312 was also registered. The results of restricted enzyme digestion indicated that eukaryotic vector pcDNA-UPⅡ for Uroplakin Ⅱ was successfully constructed. After being transferred with pcDNA-UPⅡ for 72 h, cellular Uroplakin Ⅱ mRNA levels were significantly improved (P<0.01). It is concluded that human Uroplakin Ⅱ gene was successfully cloned from Chinese TCC tissues, which provided a basis for further exploration of the roles of Uroplakin Ⅱ gene in TCC biological behaviors and potential strategies for targeted biological therapy of TCC.

Research on the prognosis of different types of microvessels in bladder transitional cell carcinoma

BACKGROUND At present,there is controversy on the role of microvessel density(MVD)in tumors as a prognostic indicator of bladder transitional cell carcinoma(BTCC).However,the MVD in tumors is simply classified based on the expression of several different vascular markers,which has not been related to analytical research on the prognosis of patients with BTCC.AIM To explore the classification of blood vessels in tumors and studied the relationship between MVD and the prognosis of patients with BTCC.METHODS The tissue mass was detected by tissue microarray and immunohistochemical analysis with monoclonal antibodies against CD31,CD34,CD105,and vascular smooth muscle actin to investigate the MVD in BTCC.The measurement data are expressed as the mean±SD.The difference between the groups was analyzed by the t-test,the counting data were analyzed byχ2 test.The Kaplan-Meier survival curve was estimated by the product-limit method.The log-rank time-series test was employed to compare the tumor-free survival curves.RESULTS The MVD was closely related to the pathological grade,invasive depth,and prognosis of BTCC.Significant differences were found between grade I and grade II,grade II and grade III,superficial and invasive type,and the tumor-free survival group and the recurrence or metastasis group(P<0.01).Multivariate analysis showed that undifferentiated MVD was an independent prognostic factor for patient survival time.An inverse correlation between undifferentiated tumor MVD and differentiated tumor MVD in BTCC was also shown.CONCLUSION The classification of blood vessels in BTCC could act as an important prognostic indicator and may also be of great significance in the treatment of cancer.

Cetuximab combined with chemotherapy for simultaneous esophageal squamous cell carcinoma and colon adenocarcinoma:A case report

BACKGROUND Multiple primary carcinomas(MPCs)are defined as two or more independent primary cancers that occur simultaneously or sequentially in the same individual.Synchronous MPCs are rarer than solitary cancers or metachronous MPCs.Accurate diagnoses of synchronous MPCs and the choice of treatment are critical for successful outcomes in these cases.CASE SUMMARY A 64-year-old patient presented with dysphagia,without obvious cause.A diagnosis of synchronous esophageal squamous cell carcinoma and colon adenocarcinoma with liver metastasis was confirmed based on examination and laboratory results.After multi-disciplinary consultations,combination chemotherapy(a 3-wk cycle with oxaliplatin 212 mg administered on day 1 and capecitabine 1.5 g twice daily on days 1-14)and esophageal cancer radiotherapy were initiated.Based on the results of genetic testing,we switched to a regimen of leucovorin+fluorouracil+oxaliplatin and cetuximab regimen for 8 cycles.Subsequently,capecitabine and bevacizumab were administered until the most recent follow-up,at which the tumor remained stable.CONCLUSION Successful cetuximab chemotherapy treatment provides a reference for the nonoperative and homogeneous treatment of different pathological types of synchronous MCPs.

Long-term follow-up of Ta transitional cell carcinoma of bladder after treatment of TURBt plus intravesical therapy

To stduy the association between the prognosis of Ta transitional cell carcinoma (TCC) of the bladder and risk-related factors.Methods A total of 88 cases (62 males and 26 females;mean age,61 years;age range,41-81 years) of initial T.TCC of the bladder treated with transurethral resection of bladder tumor (TURBt) plus intravesical chemotherapy or immunotherapy were enrolled.Among them,there were 26 cases of G1,61 cases of G2 and 1 case of G3.For tumor site,62 cases (16 cases of G1,45 of G2,1 of G3) had single tumor and 26 cases (10 cases of G1,16 of G2) had multi-site tumors.The mean follow-up was 113 months (range,56-168 months).The tumor grade,original tumor number and their association with the recurrence and progression of this type of TCC were retrospectively analyzed.Results The overall recurrence rate (RR) was 60% (53/88).In single tumor group,RR of G1 cases was 25% (4/16);RR of G2 cases was 62% (28/45) and the total RR was 52% (32/62).In multi-site tumor group,RR of G1 cases was 80% (8/10),RR of G2 cases was 75% (12/16) and the total RR was 77% (20/26).The RR of multi-site tumor group was significantly higher than that of single tumor group (P<0.01).In single tumor group,RR of G2 cases was significantly higher than that of G1 cases (P<0.001).In multi-site tumor group,there was no association of RR with tumor grade.There was no progression in G1 tumor cases.The progression rate was 42.5% (17/40) in G2 tumor cases;among them,30% (12/40) progressed to T1G2 tumors and 12.5% (5/40) progressed to T2G2 tumors.The RR of cases who received thiotepa,mitomycin and BCG were 75% (12/16),68% (30/44) and 40% (11/27),respectively.Tumor specific mortality was 1.14% (1/88,a T2G3 case).Conclusion The multi-site Ta TCC of the bladder has relatively higher RR and greater chance of progression after the treatment of TURBt plus intravesical chemotherapy or immunotherapy,especially in the poor differentiated tumors,thus active treatment and close follow-up are essential in clinical practice.9 refs.

Plasmacytoid Transitional Cell Carcinoma of Bladder： A Clinico-pathological Study and Review of Literatures

客观：学习血浆的病理学的特征，并且分析诊断特征，为鉴别诊断的标准和肿瘤的临床的意义膀胱的似细胞的过渡房间癌。方法：膀胱 plasmacytoidtransitional 房间癌的二个盒子被学习。平淡的石蜡节与他染色，由 S-P 方法的奶头油迹 andimmunohistochemistry 在一台轻显微镜下面被观察。病理学、临床的数据被比较在文学与早报导的案例分析。结果：这个肿瘤的 Acharacteristic 特征具有在薄板 propria 或 muscularispropria 的深侵略，除了在粘膜的原位癌的部件，当肿瘤被诊断时。组织学的模式和 cytological 特征显示出类似到 plasmacytoidtumor。肿瘤房间为 AE1/AE3， CEA 和 CK18 是强烈积极的。预后看起来比平常的过渡房间癌更坏。结论：血浆膀胱的似细胞的过渡房间癌是稀罕的，但是有典型病理学，免疫组织学、临床的特征。病理学家们应该知道膀胱的这种原发性瘤。

Myocardial metastasis from ZEB1-and TWIST-positive spindle cell carcinoma of the esophagus:A case report

BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.

TuBG1 promotes hepatocellular carcinoma via ATR/P53-apoptosis and cycling pathways

Background:As reported,γ-tubulin(TuBG1)is related to the occurrence and development of various types of malignant tumors.However,its role in hepatocellular cancer(HCC)is not clear.The present study was to investigate the relationship between TuBG1 and clinical parameters and survival in HCC patients.Methods:The correlation between TuBG1 and clinical parameters and survival in HCC patients was ex-plored by bioinformatics analysis.Immunohistochemistry was used for the verification.The molecular function of TuBG1 was measured using colony formation,scratch assay,trans-well assay and flow cytometry.Gene set enrichment analysis(GSEA)was used to pick up the enriched pathways,followed by investigating the target pathways using Western blotting.The tumor-immune system interactions and drug bank database(TISIDB)was used to evaluate TuBG1 and immunity.Based on the TuBG1-related immune genes,a prognostic model was constructed and was further validated internally and externally.Results:The bioinformatic analysis found high expressed TuBG1 in HCC tissue,which was confirmed us-ing immunohistochemistry and Western blotting.After silencing the TuBG1 in HCC cell lines,more G1 arrested cells were found,cell proliferation and invasion were inhibited,and apoptosis was promoted.Furthermore,the silence of TuBG1 increased the expressions of Ataxia-Telangiectasia and Rad-3(ATR),phospho-P38 mitogen-activated protein kinase(P-P38MAPK),phospho-P53(P-P53),B-cell lymphoma-2 associated X protein(Bax),cleaved caspase 3 and P21;decreased the expressions of B-cell lymphoma-2(Bcl-2),cyclin D1,cyclin E2,cyclin-dependent kinase 2(CDK2)and CDK4.The correlation analysis of immunohistochemistry and clinical parameters and survival data revealed that TuBG1 was negatively corre-lated with the overall survival.The constructed immune prognosis model could effectively evaluate the prognosis.Conclusions:The increased expression of TuBG1 in HCC is associated with poor prognosis,which might be involved in the occurrence and development of HCC.

Latest insights into the global epidemiological features,screening,early diagnosis and prognosis prediction of esophageal squamous cell carcinoma

As a highly invasive carcinoma,esophageal cancer(EC)was the eighth most prevalent malignancy and the sixth leading cause of cancer-related death worldwide in 2020.Esophageal squamous cell carcinoma(ESCC)is the major histological subtype of EC,and its incidence and mortality rates are decreasing globally.Due to the lack of specific early symptoms,ESCC patients are usually diagnosed with advanced-stage disease with a poor prognosis,and the incidence and mortality rates are still high in many countries,especially in China.Therefore,enormous challenges still exist in the management of ESCC,and novel strategies are urgently needed to further decrease the incidence and mortality rates of ESCC.Although the key molecular mechanisms underlying ESCC pathogenesis have not been fully elucidated,certain promising biomarkers are being investigated to facilitate clinical decision-making.With the advent and advancement of highthroughput technologies,such as genomics,proteomics and metabolomics,valuable biomarkers with high sensitivity,specificity and stability could be identified for ESCC.Herein,we aimed to determine the epidemiological features of ESCC in different regions of the world,especially in China,and focused on novel molecular biomarkers associated with ESCC screening,early diagnosis and prognosis prediction.

MicroRNAs in hepatocellular carcinoma treatment:Charting the path forward

MicroRNAs(miRNAs)are recognized for their involvement in the regulation of gene expression and exhibit significant potential in both the prognostic assessment and treatment of hepatocellular carcinoma(HCC).HCC,like other tumors,seldom occurs in isolation;instead,it evolves within a microenvironment featuring oncogenic and tumor-suppressive elements.When combined with suitable delivery vehicles,miRNA technology provides the capability to directly engage with these elements,thereby hindering tumor formation and progression.Ongoing research in this domain holds the promise of enabling a more efficacious and multi-modal treatment approach for HCC in the near future.

Metadherin promotes stem cell phenotypes and correlated with immune infiltration in hepatocellular carcinoma

BACKGROUND Metadherin(MTDH)is a key oncogene in most cancer types,including hepato-cellular carcinoma(HCC).Notably,MTDH does not affect the stemness pheno-type or immune infiltration of HCC.AIM To explore the role of MTDH on stemness and immune infiltration in HCC.METHODS MTDH expression in HCC tissues was detected using TCGA and GEO databases.Immunohistochemistry was used to analyze the tissue samples.MTDH was stably knocked down or overexpressed by lentiviral transfection in the two HCC cell lines.The invasion and migration abilities of HCC cells were evaluated using Matrigel invasion and wound healing assays.Next,we obtained liver cancer stem cells from the spheroids by culturing them in a serum-free medium.Gene expression was determined by western blotting and quantitative reverse transcri-ption PCR.Flow cytometry,immunofluorescence,and tumor sphere formation assays were used to characterize stem-like cells.The effects of MTDH inhibition on tumor growth were evaluated in vivo.The correlation of MTDH with immune cells,immunomodulators,and chemokines was analyzed using ssGSEA and TISIDB databases.RESULTS HCC tissues expressed higher levels of MTDH than normal liver tissues.High MTDH expression was associated with a poor prognosis.HCC cells overex-pressing MTDH exhibited stronger invasion and migration abilities,exhibited a stem cell-like phenotype,and formed spheres;however,MTDH inhibition attenuated these effects.MTDH inhibition suppressed HCC progression and CD133 expression in vivo.MTDH was positively correlated with immature dendritic,T helper 2 cells,central memory CD8^(+)T,memory B,activated dendritic,natural killer(NK)T,NK,activated CD4^(+)T,and central memory CD4^(+)T cells.MTDH was negatively correlated with activated CD8^(+)T cells,eosinophils,activated B cells,monocytes,macrophages,and mast cells.A positive correlation was observed between the MTDH level and CXCL2 expression,whereas a negative correlation was observed between the MTDH level and CX3CL1 and CXCL12 expression.CONCLUSION High levels of MTDH expression in patients with HCC are associated with poor prognosis,promoting tumor stemness,immune infiltration,and HCC progression.

Hydrangea serrata extract exerts tumor inhibitory activity against hepatocellular carcinoma HepG2 cells via inducing p27/CDK2-mediated cell cycle arrest and apoptosis

Objective:To examine the inhibitory effect of Hydrangea serrata extract against hepatocellular carcinoma HepG2 cells and its underlying mechanisms.Methods:The effects of Hydrangea serrata extract on growth inhibition of tumor cells and spheroids were assessed using MTT and 3D culture assays.Quantitative real-time PCR and Western blot analyses were employed to investigate the changes in mRNA and protein expression levels of molecules related to cell cycle and apoptosis.Results:Hydrangea serrata extract effectively inhibited the growth of both tumor cells and spheroids.The extract also significantly upregulated p27 mRNA expression and downregulated CDK2 mRNA expression,leading to cell cycle arrest.Moreover,increased BAX/Bcl-2 ratio as well as caspase-9 and-3 were observed after treatment with Hydrangea serrata extract,indicating the induction of tumor cell apoptosis.Conclusions:Hydrangea serrata extract has the potential to alleviate tumors by effectively modulating cell-cycle-related gene expressions and inducing apoptosis,thereby inhibiting tumor growth.

Hypomethylation of glycine dehydrogenase promoter in peripheral blood mononuclear cells is a new diagnostic marker of hepatitis B virus-associated hepatocellular carcinoma

Background: Glycine dehydrogenase(GLDC) plays an important role in the initiation and proliferation of several human cancers. In this study, we aimed to detect the methylation status of GLDC promoter and its diagnostic value for hepatitis B virus-associated hepatocellular carcinoma(HBV-HCC). Methods: We enrolled 197 patients, 111 with HBV-HCC, 51 with chronic hepatitis B(CHB), and 35 healthy controls(HCs). The methylation status of GLDC promoter in peripheral mononuclear cells(PBMCs) was identified by methylation specific polymerase chain reaction(MSP). The mRNA expression was examined using real-time quantitative polymerase chain reaction(q PCR). Results: The methylation frequency of the GLDC promoter was significantly lower in HBV-HCC patients(27.0%) compared to that in CHB patients(68.6%) and HCs(74.3%)( P < 0.001). The methylated group had lower alanine aminotransferase level( P = 0.035) and lower rates of tumor node metastasis(TNM) Ⅲ/Ⅳ( P = 0.043) and T3/T4( P = 0.026). TNM stage was identified to be an independent factor for GLDC promoter methylation. GLDC mRNA levels in CHB patients and HCs were significantly lower than those in HBV-HCC patients( P = 0.022 and P < 0.001, respectively). GLDC mRNA levels were significantly higher in HBV-HCC patients with unmethylated GLDC promoters than those with methylated GLDC promoters( P = 0.003). The diagnostic accuracy of alpha-fetoprotein(AFP) combined with GLDC promoter methylation for HBV-HCC was improved compared with that of AFP alone(AUC: 0.782 vs. 0.630, P < 0.001). In addition, GLDC promoter methylation was an independent predictor for overall survival of HBV-HCC patients( P = 0.038). Conclusions: The methylation frequency of GLDC promoter was lower in PBMCs from HBV-HCC patients than that from patients with CHB and HCs. The combination of AFP and GLDC promoter hypomethylation significantly improved the diagnostic accuracy of HBV-HCC.

MicroRNAs:A novel signature in the metastasis of esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC)is a malignant epithelial tumor,characterized by squamous cell differentiation,it is the sixth leading cause of cancer-related deaths globally.The increased mortality rate of ESCC patients is predominantly due to the advanced stage of the disease when discovered,coupled with higher risk of metastasis,which is an exceedingly malignant charac-teristic of cancer,frequently leading to a high mortality rate.Unfortunately,there is currently no specific and effective marker to predict and treat metastasis in ESCC.MicroRNAs(miRNAs)are a class of small non-coding RNA molecules,approximately 22 nucleotides in length.miRNAs are vital in modulating gene expression and serve pivotal regulatory roles in the occurrence,progression,and prognosis of cancer.Here,we have examined the literature to highlight the intimate correlations between miRNAs and ESCC metastasis,and show that ESCC metastasis is predominantly regulated or regulated by genetic and epigenetic factors.This review proposes a potential role for miRNAs as diagnostic and therapeutic biomarkers for metastasis in ESCC metastasis,with the ultimate aim of reducing the mortality rate among patients with ESCC.

Role of deubiquitinase JOSD2 in the pathogenesis of esophageal squamous cell carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a deadly malignancy with limited treatment options.Deubiquitinases(DUBs)have been confirmed to play a crucial role in the development of malignant tumors.JOSD2 is a DUB involved in con-trolling protein deubiquitination and influencing critical cellular processes in cancer.AIM To investigate the impact of JOSD2 on the progression of ESCC.METHODS Bioinformatic analyses were employed to explore the expression,prognosis,and enriched pathways associated with JOSD2 in ESCC.Lentiviral transduction was utilized to manipulate JOSD2 expression in ESCC cell lines(KYSE30 and RESULTS )Preliminary research indicated that JOSD2 was highly expressed in ESCC tissues,which was associated with poor prognosis.Further analysis demonstrated that JOSD2 was upregulated in ESCC cell lines compared to normal esophageal cells.JOSD2 knockdown inhibited ESCC cell activity,including proliferation and colony-forming ability.Moreover,JOSD2 knockdown decreased the drug resistance and migration of ESCC cells,while JOSD2 overexpression enhanced these phenotypes.In vivo xenograft assays further confirmed that JOSD2 promoted tumor proliferation and drug resistance in ESCC.Mechanistically,JOSD2 appears to activate the MAPK/ERK and PI3K/AKT signaling pathways.Mass spectrometry was used to identify crucial substrate proteins that interact with JOSD2,which identified the four primary proteins that bind to JOSD2,namely USP47,IGKV2D-29,HSP90AB1,and PRMT5.CONCLUSION JOSD2 plays a crucial role in enhancing the proliferation,migration,and drug resistance of ESCC,suggesting that JOSD2 is a potential therapeutic target in ESCC.

Using MsfNet to Predict the ISUP Grade of Renal Clear Cell Carcinoma in Digital Pathology Images

Clear cell renal cell carcinoma(ccRCC)represents the most frequent form of renal cell carcinoma(RCC),and accurate International Society of Urological Pathology(ISUP)grading is crucial for prognosis and treatment selection.This study presents a new deep network called Multi-scale Fusion Network(MsfNet),which aims to enhance the automatic ISUP grade of ccRCC with digital histopathology pathology images.The MsfNet overcomes the limitations of traditional ResNet50 by multi-scale information fusion and dynamic allocation of channel quantity.The model was trained and tested using 90 Hematoxylin and Eosin(H&E)stained whole slide images(WSIs),which were all cropped into 320×320-pixel patches at 40×magnification.MsfNet achieved a micro-averaged area under the curve(AUC)of 0.9807,a macro-averaged AUC of 0.9778 on the test dataset.The Gradient-weighted Class Activation Mapping(Grad-CAM)visually demonstrated MsfNet’s ability to distinguish and highlight abnormal areas more effectively than ResNet50.The t-Distributed Stochastic Neighbor Embedding(t-SNE)plot indicates our model can efficiently extract critical features from images,reducing the impact of noise and redundant information.The results suggest that MsfNet offers an accurate ISUP grade of ccRCC in digital images,emphasizing the potential of AI-assisted histopathological systems in clinical practice.

Primary acinic cell carcinoma of the breast: A case report and review of literature

BACKGROUND In the current World Health Organization classification,acinic cell carcinoma(AcCC)of the breast is considered a rare histological subtype of triple-negative breast cancer.Because of the few reports in the literature,data concerning clinical outcomes are limited.Here,we report a case of AcCC of the breast in a 48-year-old woman.A 48-year-old woman with a mass in her right breast came to our hospital for further diagnosis.Mammography and an ultrasound(US)scan showed a mass in the upper inner side of the right breast.She then underwent surgery to resect the mass in her right breast.Postoperative pathological examination revealed that the tumor had abundant acinar-like structures formed by tumor cells with prominent eosinophilic granules in the cytoplasm,consistent with acinar cell carcinoma.The results of immunohistochemical analysis supported the diagnosis of breast acinar cell carcinoma.Two months later,she underwent breast-conserving surgery and sentinel lymph node biopsy.The pTNM stage was T2N0M0.After surgery,the patient received 30 radiotherapy sessions.The patient was followed up for a period of one year,and no recurrence was found.AcCC of the breast is a rare type of malignant tumor.Because it is usually asym-ptomatic and can be detected by imaging studies,routine breast US or mamm-ograms are important.However,there are no characteristic diagnostic imaging findings or clinical manifestations,so immunohistochemical examination is critical for an accurate diagnosis of AcCC of the breast.