This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and ...This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and FAO datasets were used to identify these key genes.Wilcoxon rank sum test was used to assess the levels of acyl-CoA dehydrogenase medium chain(ACADM)between KIRC and non cancer samples.The logistic regression and Wilcoxon rank sum test were used to explore the association between ACADM and clinical features.The diagnostic performance of ACADM for KIRC was asessed using a diagnostic receiver operating ch aracteristic(ROC)curve.The co-expressed genes of ACADM were identifed in LinkedOmics database,and their function and pathway enrichment were analyzed.The correlation between ACADM expression level and immune infitration was analyzed by Gene Set Variation Analysis(GSVA)method Additionally,the proliferation,migration,and invasion abilities of KIRC cells were assessed after overexpressing ACADM.Following differential analysis and intersection,we identifed six hub genes,induding ACADM.We found that the expression level of ACADM was decreased in KIRC tissues and had a better diagnostic efect(AUC=0.916).Survival analysis suggested that patients with decreased ACADM expression had a worse prognosis.According to correlation analysis,a variety of dinical features were associated with the expression level of ACADML By analyzing the infiltration level of immune cells,we found that ACADM may be related to the enrichment of immune cells.Finally,ACADM overexpression inhibited proliferation,migration,and invasion of KIRC cells.In conclusion,our findings suggest that reduced ACADM expression in KIRC patients is indicative of poor prognosis.These results imply that ACADM may be a diagnostic and prognostic marker for individuals with KIRC,offering a reference for dinicians in diagnosis and treatment.展开更多
EVI2A has emerged as a significant biomarker in various diseases;however,its biological role and mechanism in kidney renal clear cell carcinoma(KIRC)remains unexplored.We used TCGA and GEO databases to analyze EVI2A g...EVI2A has emerged as a significant biomarker in various diseases;however,its biological role and mechanism in kidney renal clear cell carcinoma(KIRC)remains unexplored.We used TCGA and GEO databases to analyze EVI2A gene expression comprehensively and performed pan-cancer assessments.Clinical relevance was evaluated through Kaplan-Meier analysis and ROC curves.The gene’s immune relevance was explored through analyses of the tumor microenvironment(TME),Tumor Immune Single-cell Hub(TISCH),immune checkpoints,and immunotherapy sensitivity.Our results indicate that EVI2A expression is upregulated in KIRC,showing correlations with tumor grade and T/N/M stage.EVI2A demonstrates high diagnostic accuracy(AUC=0.906)and predicts poor overall and progression-free survival in KIRC patients.Furthermore,EVI2A expression exhibits significant associations with immunity,including TME scores and specific immune cell types such as Tfh cells,CD4 memory T cells,and CD8+T cells.Elevated EVI2A expression suggests increased sensitivity to PD-1/CTLA-4 and tyrosine kinase inhibitors.In vitro assays confirmed the impact of EVI2A on KIRC behavior,with its knockdown resulting in reduced cell proliferation and migration.In conclusion,our comprehensive analysis identifies EVI2A as a promising biomarker and a novel therapeutic target for intervening in KIRC.These findings hold significant implications for further research and potential clinical applications.展开更多
BACKGROUND Endobronchial metastases(EBMs)are tumours that metastasise from a malignant tumour outside the lungs to the central and subsegmental bronchi,and are visible under a bronchofibrescope.Most EBMs are formed by...BACKGROUND Endobronchial metastases(EBMs)are tumours that metastasise from a malignant tumour outside the lungs to the central and subsegmental bronchi,and are visible under a bronchofibrescope.Most EBMs are formed by direct invasion or metastasis of intrathoracic malignant tumours,such as lung cancer,oesophageal cancer or mediastinum tumours.Renal cell carcinoma(RCC),accounting for 2%to 3%of all tumours,is a common malignant tumour of the urinary system.Renal clear cell carcinoma(RCCC)constitutes the predominant pathological subtype of RCC,comprising approximately 70%to 80%of all RCC cases.RCCC can spread and metastasise through arterial,venous and lymphatic circulation to almost all organs of the body.Moreover,lung,bone,liver,brain and local recurrence are the most common metastatic neoplasms of RCCC.However,EBM from RCCC has a low complication rate and is often misdiagnosed as primary lung cancer.CASE SUMMARY A 71-year-old male patient who had undergone radical left nephrectomy 7 years prior due to RCCC was referred to our hospital due to a 1-mo history of productive cough.The results of an enhanced chest CT scan indicated the presence of a soft tissue nodule in the upper lobe of the left lung,and flexible bronchoscopy revealed a hypervascular lesion in the bronchus of the left lung's superior lobe.Therefore,the patient underwent thoracoscopic left superior lobe wedge resection,and pathology confirmed EBM from the RCCC.CONCLUSION EBM from RCCC has a low incidence and no characteristic clinical manifestations in the early stage.If a bronchial tumour is found in a patient with RCCC,the possibility of bronchial metastatic cancer should be considered.展开更多
AIM:To clarify the therapeutic strategies and prognosis factors of primary clear cell carcinoma of the liver(PCCCL) . METHODS:The clinical pathological data of 64 patients with PCCCL treated with hepatectomy in our ho...AIM:To clarify the therapeutic strategies and prognosis factors of primary clear cell carcinoma of the liver(PCCCL) . METHODS:The clinical pathological data of 64 patients with PCCCL treated with hepatectomy in our hospital from January 2000 to January 2006 were analyzed retrospectively.The patients were divided into two groups to make treatment analysis:curative resection only(n=40) ;and curative resection and postoperative chemotherapy with calcium folinate and tegafur(n= 24) .Meanwhile,the PCCCL patients were subdivided into two subgroups on the basis of the proportion of clear cells in the tumor for pathological analysis.There were 36 cases in subgroup A for which the proportion of clear cells was more than 70%,and 28 cases in subgroup B for which the proportion was less or equal to 70%,comparing analysis of median survival time of the counterpart groups.Univariate and multivariate analyses were performed to examine factors that affect-ed clinical prognosis,recurrence and metastasis. RESULTS:Median survival period of the curative surgery group was 38 mo,while the counterpart was 41 mo.Median survival period for group A was 41 mo,while group B was 19 mo.The Kaplan-Meier method showed that capsule formation,preoperative liver function,hepatitis C virus infection,large vascular invasion and multiple tumor occurrences were related to disease-free survival.Cox regression analysis showed that the clear cell ratio,capsule formation,preoperative liver function and large vascular invasion were independent risk factors for overall survival. CONCLUSION:Postoperative chemotherapy has no obvious effect on survival of patients with PCCCL. Clear cell ratio,capsule formation,preoperative liver function,and vascular invasion were independent risk factors for prognosis.展开更多
AIM: To retrospectively analyze the computed tomography (CT) and magnetic resonance imaging (MRI) appearances of primary clear cell carcinoma of the liver (PCCCL) and compare the imaging appearances of PCCCL and commo...AIM: To retrospectively analyze the computed tomography (CT) and magnetic resonance imaging (MRI) appearances of primary clear cell carcinoma of the liver (PCCCL) and compare the imaging appearances of PCCCL and common type hepatocellular carcinoma (CHCC) to determine whether any differences exist between the two groups. METHODS: Twenty cases with pathologically proven PCCCL and 127 cases with CHCC in the Second Affiliated Hospital of Sun Yat-sen University were included in this study. CT or MRI images from these patients were retrospectively analyzed. The following imaging findings were reviewed: the presence of liver cirrhosis, tumor size, the enhancement pattern on dynamic contrast scanning, the presence of pseudo capsules, tumor rupture, portal vein thrombosis and lymph node metastasis. RESULTS: Both PCCCL and CHCC were prone to occur in patients with liver cirrhosis, the association rate of liver cirrhosis was 80.0% and 78.7%, respectively (P > 0.05). The mean sizes of PCCCL and CHCC tumors were (7.28 ± 4.25) cm and (6.96 ± 3.98) cm, respectively. Small HCCs were found in 25.0% (5/20) of PCCCL and 19.7% (25/127) of CHCC cases. No significant differences in mean size and ratio of small HCCs were found between the two groups (P = 0.658 and 0.803, respectively). Compared with CHCC patients, PCCCL patients were more prone to form pseudo capsules (49.6% vs 75.0%, P = 0.034). Tumor rupture, typical HCC enhancement patterns and portal vein tumor thrombosis were detected in 15.0% (3/20), 72.2% (13/18) and 20.0% (4/20) of patients with PCCCL and 3.1% (4/127), 83.6% (97/116) and 17.3% (22/127) of patients with CHCC, respectively. There were no significant differences between the two groups (all P > 0.05). No patients with PCCCL and 2.4% (3/127) of patients with CHCC showed signs of lymph node metastasis (P > 0.05). CONCLUSION: The imaging characteristics of PCCCL are similar to those of CHCC and could be useful for differentiating these from other liver tumors (such as hemangioma and hepatic metastases). PCCCLs are more prone than CHCCs to form pseudo capsules.展开更多
Objective:To study the correlation between hyaluronic acid(HA),hyaluronic acid synthase(HAS) and human renal clear cell carcinoma(RCCC).Methods:The expression of three HAS isoforms' gene and HA in 93 RCCC tis...Objective:To study the correlation between hyaluronic acid(HA),hyaluronic acid synthase(HAS) and human renal clear cell carcinoma(RCCC).Methods:The expression of three HAS isoforms' gene and HA in 93 RCCC tissues,27 nephridial tissues by the side of RCCC from two hospitals were measured with Real-Time RT-PCR、Western Blot and immunohistochemical methods and analyzed.Results:All RCCC and adjacent normal tissues expressed three HASs' mRNA protein;at the mRNA level,both RCCC and adjacent normal tissues,expressed more HAS3 than HAS1 or HAS2,their differences were statistically significant(all P values 0.05);but,at the protein level,all HAS isoforms presented the equivalent expression.Compared with the adjacent non-neoplastic kidney tissues,the expression of all HAS isoforms' mRNA in RCCC tissues were increased evidently and their differences were significant(all P values 0.0001);but at the protein level,only the expression of HAS3 increased evidently(P=0.022).In all adjacent normal tissues,more than 80% renal tubular cells strongly expressed HA,however,only the minority RCCC cases(16/93) presented weakly positive HA staining in few cancer nests(5%-30%),the difference were significant(P0.0001).In RCCC tissues subgrouped according to clinical stage,pathological grade,lymphatic metastasis or not and distant metastasis or not,the HASs' mRNA protein differential expression all had no statistical significance(all P values 0.05).Conclusion:Different from other malignancy,HA and HASs(except for HAS3) may not play important roles in the biological progress of human RCCC.展开更多
BACKGROUND Hyalinizing clear cell carcinoma(HCCC)is an uncommon tumor that originates in the salivary glands.This neoplasia constitutes less than 1%of minor salivary gland tumors.CASE SUMMARY A 67-year-old female visi...BACKGROUND Hyalinizing clear cell carcinoma(HCCC)is an uncommon tumor that originates in the salivary glands.This neoplasia constitutes less than 1%of minor salivary gland tumors.CASE SUMMARY A 67-year-old female visited the maxillofacial surgery department owing to a smooth,slightly yellowish protruding mass on the left side of the floor of the mouth,at the level of the molars;the tumor mass had a soft consistency on palpation and did not adhere to deep planes.The microscopical analysis of the excisional biopsy showed that the lesion was composed of sheets and cords of clear cells separated by thick eosinophilic bands of hyaline collagen.Normal glandular tissue was absent,periodic acid-Schiff with and without diastase stains,and immunohistochemical reactions were performed to confirm the diagnosis.This is the second case reported in the literature of HCCC arising in the floor of the mouth.CONCLUSION HCCC is a rare salivary gland tumor that has not been studied extensively.Its diagnosis is usually challenging,because clinically,it can be confused with a benign neoplasm.展开更多
The chemokine ligand 13-chemokine receptor 5(CXCL13-CXCR5)axis has been characterized as a critical tumor-promoting signaling pathway in the tumor microenvironment(TME)in multiple types of solid tumors.In this study,w...The chemokine ligand 13-chemokine receptor 5(CXCL13-CXCR5)axis has been characterized as a critical tumor-promoting signaling pathway in the tumor microenvironment(TME)in multiple types of solid tumors.In this study,we analyzed the expression profile of CXCL13 in kidney clear cell carcinoma(KIRC)and its correlation with tumor-infiltrating immune cells(TIICs).A monoclonal antibody against CXCL13 with high affinity and purity was generated in our lab for western blot and immunohistochemistry(IHC).Bioinformatic analysis was performed based on bulk-seq data from the Cancer Genome Atlas(TCGA)-KIRC and single-cell RNA-seq data from scRNASeqDB and PanglaoDB.Results showed that high CXCL13 expression in TME was associated with shorter progression-free survival(PFS),disease-specific survival(DSS),and overall survival(OS).KIRC cell lines,as well as several other cancer cell lines,had negative CXCL13 expression.IHC staining from the Human Protein Atlas(HPA)and our tissue array indicated that CXCL13 might be mainly expressed by TIICs,but not KIRC tumor cells.CXCL13 expression was strongly and positively correlated withγδT cell abundance in TME.Besides,γδT cell infiltration was associated with poor survival of KIRC.Methylation 450k array data showed that CXCL13 promoter hypomethylation was common in TIICs.The methylation level of cg16361705 within the CXCL13 promoter might play an important role in modulating CXCL13 transcription.In conclusion,our study revealed that CXCL13 expression andγδT cell infiltration in TME is associated with unfavorable survival of KIRC.TIICs,most possiblyγδT cells,are the dominant source of CXCL13 in KIRC TME.展开更多
BACKGROUND Renal clear cell carcinoma(RCC)is a malignant tumor of the genitourinary system with a predilection for males.The most common metastatic sites are the lung,liver,lymph nodes,contralateral kidney or adrenal ...BACKGROUND Renal clear cell carcinoma(RCC)is a malignant tumor of the genitourinary system with a predilection for males.The most common metastatic sites are the lung,liver,lymph nodes,contralateral kidney or adrenal gland,however,skin metastasis has only been seen in 1.0%-3.3%of cases.The most common site of skin metastasis is the scalp,and metastasis to the nasal ala region is rare.CASE SUMMARY A 55-year-old man with clear cell carcinoma of the left kidney was treated with pembrolizumab and axitinib for half a year after surgery and was found to have a red mass on his right nasal ala for 3 mo.The skin lesion of the patient grew rapidly to the size of 2.0 cm×2.0 cm×1.2 cm after discontinuation of targeted drug therapy due to the coronavirus disease 2019 epidemic.The patient was finally diagnosed with skin metastasis of RCC in our hospital.The patient refused to undergo surgical resection and the tumor shrank rapidly after resuming target therapy for 2 wk.CONCLUSION It is rare for an RCC to metastasize to the skin of the nasal ala region.The tumor size change of this patient before and after treatment with targeted drugs shows the effectiveness of combination therapy for skin metastasis.展开更多
BACKGROUND To investigate the clinicopathological features of endometrial clear cell carcinoma that has invaded the right oviduct with a cooccurring ipsilateral oviduct adenomatoid tumor.CASE SUMMARY A case of endomet...BACKGROUND To investigate the clinicopathological features of endometrial clear cell carcinoma that has invaded the right oviduct with a cooccurring ipsilateral oviduct adenomatoid tumor.CASE SUMMARY A case of endometrial clear cell carcinoma invading the right oviduct with a cooccurring ipsilateral oviduct adenomatoid tumor was collected and analyzed using pathomorphology and immunohistochemistry.Endometrial clear cell carcinoma cells were distributed in a solid nest,papillary,shoe nail-like,and glandular tube-like distribution.There was infiltrative growth,and tumor cells had clear cytoplasm and obvious nuclear heteromorphism.The cancer tissue was necrotic and mitotic.The cancer tissue invaded the right oviduct.The ipsilateral oviduct also had an adenomatoid tumor.The adenomatoid tumor was arranged in microcapsules lined with flat or cubic cells that were surrounded by smooth muscle tissue.The adenomatoid tumor cells were round in shape.CONCLUSION Clear cell carcinoma of the endometrium can invade the oviduct and occur simultaneously with tubal adenomatoid tumors.Upon pathological diagnosis,one should pay close attention to distinguishing whether an endometrial clear cell carcinoma is invading the oviduct or whether it is accompanied by an adenomatoid tumor of the oviduct.Immunohistochemistry is helpful to differentiate these two disease entities.Endometrial clear cell carcinomas express Napsin-A and P16 and are negative for estrogen receptor and progesterone receptor.The presence of endometrial clear cell carcinoma does not affect the expression of CK and calretinin in adenomatoid tumors.展开更多
Medullary sponge kidney(MSK)is a characteristic renal malformation,with a relatively low incidence.Radiologically,identification of MSK is sometimes ambiguous when compared to a renal mass.Here,we report a novel renal...Medullary sponge kidney(MSK)is a characteristic renal malformation,with a relatively low incidence.Radiologically,identification of MSK is sometimes ambiguous when compared to a renal mass.Here,we report a novel renal clear cell carcinoma in MSK,and discuss our approach to treatment.We recommended that a preoperative biopsy should be performed,followed by a comprehensive discussion regarding the appropriate perioperative preparations and careful surgical techniques that should be performed for this complex disease.展开更多
Clear cell carcinoma (CCC) of the uterine cervix is rare, and its etiology is unclear, except for reports of prenatal diethylstilbestrol (DES) exposure. In this case report of a 78-year-old postmenopausal Japanese wom...Clear cell carcinoma (CCC) of the uterine cervix is rare, and its etiology is unclear, except for reports of prenatal diethylstilbestrol (DES) exposure. In this case report of a 78-year-old postmenopausal Japanese woman with pelvic endometriosis, cervical CCC presented as a deep interstitial tumor, strongly suggesting the patient suffered from cervical endometriosis for a long time. A </span><span style="font-family:Verdana;">cystic lesion without solid components was detected in the uterine cervix.</span><span style="font-family:Verdana;"> Although the patient had regular gynecological examinations every 6 months, she presented 5 years later with a complaint of watery vaginal discharge. Ul</span><span style="font-family:Verdana;">trasonography and magnetic resonance imaging (MRI) detected a uterine</span><span style="font-family:Verdana;"> cervical cystic mass with a solid component. Although no malignancy was confirmed preoperatively, surgery was performed under a high suspicion of cervical cancer. Intraoperative pathology revealed CCC in a solid tumor, so debulking surgery, including lymphadenectomy, was done. Endometrial tissue was found adjacent to the tumor, strongly suggesting the tumor arose from cervical endometriosis. Because endometriosis in ectopic sites carries a risk of </span><span style="font-family:Verdana;">carcinogenesis, as is the case in ovarian endometriosis, it may be recom</span><span style="font-family:Verdana;">mended that a cervical cystic lesion with pelvic endometriosis should be followed up regularly for the early detection of uterine cancer.展开更多
Primary clear cell carcinoma of the nasopharynx is a rare and locally invasive minor salivary gland neoplasm,only two cases have been reported yet in the literature.Now a 57-year man,with primary nasopharyngeal clear ...Primary clear cell carcinoma of the nasopharynx is a rare and locally invasive minor salivary gland neoplasm,only two cases have been reported yet in the literature.Now a 57-year man,with primary nasopharyngeal clear carcinoma,received radiotherapy and chemotherapy.After treatment,the mass of nasopharynx visibly reduced.Follow-up two months and repeated MRI,CT,abdominal B-ultrasonograpy,electronic nasopharyngoscopy,no tumor recurrence or metastasis.展开更多
Primary clear cell carcinoma of the breast is a rare tumor with different morphological characteristics compared to ordinary breast carcinomas. The clear cell morphology of the neoplastic population in these tumors ha...Primary clear cell carcinoma of the breast is a rare tumor with different morphological characteristics compared to ordinary breast carcinomas. The clear cell morphology of the neoplastic population in these tumors has been ascribed to the presence of intracellular lipid, mucin or glycogen, or to myoepithelaial, apocrine, or neuroendocrine differentiation. We describe 2 cases of glycogen-rich clear cell carcinoma of the breast as follows.展开更多
This report documents a rare case of complete spontaneous regression of clear cell carcinoma of the endometrium. An elderly woman with paranoid schizophrenia was admitted to the hospital because of vaginal bleeding. D...This report documents a rare case of complete spontaneous regression of clear cell carcinoma of the endometrium. An elderly woman with paranoid schizophrenia was admitted to the hospital because of vaginal bleeding. Diagnostic curetting and biopsy were performed and she was diagnosed with clear cell carcinoma of endometrium. Anti-tumour therapy was not possible because of her poor psychiatric status. 13 months later the woman died of a natural cause and at autopsy the endometrial tumour could no longer be identified. Myocardial infarction, aggravated by poor functional status of organism due to sepsis, was concluded to be the cause of death.展开更多
Background: Ovarian clear cell carcinoma (CCC) is often diagnosed at stage I. However, because of the poor prognosis of recurrent cases, even for stage Ia CCC, treatment strategies such as expansion of fertility-spari...Background: Ovarian clear cell carcinoma (CCC) is often diagnosed at stage I. However, because of the poor prognosis of recurrent cases, even for stage Ia CCC, treatment strategies such as expansion of fertility-sparing treatment and omission of adjuvant chemotherapy have been carefully discussed in recent years. We previously reported the possibility of the maximum standardized uptake value (SUVmax) as a biomarker of CCC prognosis prediction at all stages. In this study, we confirmed differences in SUVmax within stage I CCC and considered treatment strategies. Methods: We selected all 31 patients with ovarian CCC stage I who underwent fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) before treatment between 2006 and 2013 at our institution. This retrospective study was based on their medical records. Results: Clinical tumor stage was Ia in 13 patients, and Ic in 18 (Ic (b) in 11, and Ic (1) + Ic (2) in seven). There were no differences in serum CA125 level, maximum tumor diameter or mural nodules. Median SUVmax was significantly higher in stage Ic (5.87) than stage Ia (3.08) cases (P = 0.02). Progression-free survival was longer in the low SUVmax group than the high SUVmax group (P = 0.08). Conclusions: SUVmax for primary lesions in CCC was significantly higher in stage Ic than stage Ia. As SUVmax represents a prognostic factor in stage I CCC, these findings may suggest SUVmax as an indicator for the application of fertility-sparing surgery and omission of adjuvant chemotherapy for stage Ia CCC.展开更多
Background:Tumor heterogeneity is closely related to the occurrence,progression and recurrence of renal clear cell carcinoma(ccRCC),making early diagnosis and effective treatment difficult.DNA methylation is an import...Background:Tumor heterogeneity is closely related to the occurrence,progression and recurrence of renal clear cell carcinoma(ccRCC),making early diagnosis and effective treatment difficult.DNA methylation is an important regulator of gene expression and can affect tumor heterogeneity.Methods:In this study,we investigated the prognostic value of subtypes based on DNA methylation status in 506 ccRCC samples with paired clinical data from the TCGA database.Differences in DNA methylation levels were associated with differences in T,N and M categories,age,stage and prognosis.Finally,the samples were divided into the training group and the testing group according to 450K and 27K.Univariate and multivariate Cox regression analysis was used to construct the prediction model in the training group,and the model was verified and evaluated in the testing group.Results:By univariate Cox regression analysis,21,122 methylation sites and 6,775 CpG sites were identified as potential DNA methylation biomarkers for overall survival of ccRCC patients(P<0.05).3,050 CpG sites independently associated with prognosis were identified with T,N,M,stage and age as covariables.Consensus cluster of 3,050 potential prognostic methylation sites was used to identify different DNA methylation subsets of ccRCC for prognostic purposes.We performed functional enrichment analysis on these 3,640 genes and identified 75 significantly enriched pathways(P<0.05).We then researched the expression of methylated genes in subgroups.Verifing with the training set,suggesting that DNA methylation levels generally reflect the expression of these genes.Conclusion:Based on TCGA database and a series of bioinformatics methods,We identified prognostic specific methylation sites and established prognostic prediction models for ccRCC patients.This model helps to identify novel biomarkers,precision drug targets and disease molecular subtypes in patients with ccRCC.Therefore,this model may be useful in predicting the prognosis,clinical diagnosis and management of patients with different epigenetic subtypes of ccRCC.展开更多
Objective To explore the diagnosis and treatment features of tuberous sclerosis complex associated renal cell carcinoma. Methods A 22-year-old boy with a childhood history of epilepsy and mental retardation pres-
Objective: Memory stem T cells(Tscm) have attracted attention because of their enhanced self-renewal, multipotent capacity, and anti-tumor capacities. However, little is known about Tscm in patients with renal clear c...Objective: Memory stem T cells(Tscm) have attracted attention because of their enhanced self-renewal, multipotent capacity, and anti-tumor capacities. However, little is known about Tscm in patients with renal clear cell carcinoma(RCC) and the role of Wnt signaling in these cells. We evaluated Tscm from RCC patients concerning their activation of Wnt signaling in vitro and explored the mechanism of preferential survival.Methods: Flow cytometry identified surface markers and cytokines produced from accumulated Tscm in the presence of the glycogen synthase kinase beta inhibitor TWS119. Apoptosis was evaluated after induction using tumor necrosis factor-alpha.Immunofluorescence and Western blot analyses were used to investigate the activation of the nuclear factor-kappa B(NF-КB)pathway.Results: RCC patients had a similar percentage of CD4^+ and CD8^+ Tscm as healthy donors. Activation of Wnt signaling by TWS119 resulted in the accumulation of Tscm in activated T cells, but reversal of differentiated T cells to Tscm was not achieved.Preferential survival of Tscm was associated with increased anti-apoptotic ability mediated downstream of the NF-КB activation pathway.Conclusions: The finding that Tscm can accumulate by Wnt signaling in vitro in blood from RCC patients will help in devising new cancer therapy strategies of Tscm-based adoptive immunotherapy, such as dendritic cell-stimulated Tscm, and T cell receptor or chimeric antigen receptor-engineered Tscm.展开更多
We report the case of a 67-year-old female who presented with a large renal mass. Gross examination of the nephrectomy specimen demonstrated a 6-cm renal mass that invaded into the renal sinus and perinephric fat. His...We report the case of a 67-year-old female who presented with a large renal mass. Gross examination of the nephrectomy specimen demonstrated a 6-cm renal mass that invaded into the renal sinus and perinephric fat. Histologic examination revealed two distinct tumor types. The first type was a conventional(clear cell) renal cell carcinoma that was of low nuclear grade and comprised the minority of the overall tumor. The second type was a high-grade collecting duct carcinoma with glandular/tubular differentiation and composed the majority of the tumor. Immunohistochemical studies demonstrated distinctive patterns of the two tumor types, thus confirming two distinct lineages. Five months postoperatively, the patient developed metastasis to the lungs and right hilar lymph node region. A fine needle aspiration of a lung nodule demonstrated a metastatic, poorly differentiated carcinoma, similar to the collecting duct carcinoma component in the kidney. Collision tumors of the kidney are rare with fewer than 10 cases reported in the literature. Our report further expands the spectrum of this rare phenomenon.展开更多
基金the National Natural Science Foundation of China(Grant Nos.82072816 and 81672553)the Natural Science Foundation of Shandong Province(Grant No.ZR2021LZY003).
文摘This research aims to identify the key fatty acid beta-oxidation(FAO)genes that are altered in kidney renal clear cell carcinoma(KIRC)and to analyze the role of these genes in KIRC The Gene Expression Omnibus(GEO)and FAO datasets were used to identify these key genes.Wilcoxon rank sum test was used to assess the levels of acyl-CoA dehydrogenase medium chain(ACADM)between KIRC and non cancer samples.The logistic regression and Wilcoxon rank sum test were used to explore the association between ACADM and clinical features.The diagnostic performance of ACADM for KIRC was asessed using a diagnostic receiver operating ch aracteristic(ROC)curve.The co-expressed genes of ACADM were identifed in LinkedOmics database,and their function and pathway enrichment were analyzed.The correlation between ACADM expression level and immune infitration was analyzed by Gene Set Variation Analysis(GSVA)method Additionally,the proliferation,migration,and invasion abilities of KIRC cells were assessed after overexpressing ACADM.Following differential analysis and intersection,we identifed six hub genes,induding ACADM.We found that the expression level of ACADM was decreased in KIRC tissues and had a better diagnostic efect(AUC=0.916).Survival analysis suggested that patients with decreased ACADM expression had a worse prognosis.According to correlation analysis,a variety of dinical features were associated with the expression level of ACADML By analyzing the infiltration level of immune cells,we found that ACADM may be related to the enrichment of immune cells.Finally,ACADM overexpression inhibited proliferation,migration,and invasion of KIRC cells.In conclusion,our findings suggest that reduced ACADM expression in KIRC patients is indicative of poor prognosis.These results imply that ACADM may be a diagnostic and prognostic marker for individuals with KIRC,offering a reference for dinicians in diagnosis and treatment.
基金the Ethics Committee of the First Affiliated Hospital of Nanchang University(Approval:(2023)CDYFYYLK(03-013)).
文摘EVI2A has emerged as a significant biomarker in various diseases;however,its biological role and mechanism in kidney renal clear cell carcinoma(KIRC)remains unexplored.We used TCGA and GEO databases to analyze EVI2A gene expression comprehensively and performed pan-cancer assessments.Clinical relevance was evaluated through Kaplan-Meier analysis and ROC curves.The gene’s immune relevance was explored through analyses of the tumor microenvironment(TME),Tumor Immune Single-cell Hub(TISCH),immune checkpoints,and immunotherapy sensitivity.Our results indicate that EVI2A expression is upregulated in KIRC,showing correlations with tumor grade and T/N/M stage.EVI2A demonstrates high diagnostic accuracy(AUC=0.906)and predicts poor overall and progression-free survival in KIRC patients.Furthermore,EVI2A expression exhibits significant associations with immunity,including TME scores and specific immune cell types such as Tfh cells,CD4 memory T cells,and CD8+T cells.Elevated EVI2A expression suggests increased sensitivity to PD-1/CTLA-4 and tyrosine kinase inhibitors.In vitro assays confirmed the impact of EVI2A on KIRC behavior,with its knockdown resulting in reduced cell proliferation and migration.In conclusion,our comprehensive analysis identifies EVI2A as a promising biomarker and a novel therapeutic target for intervening in KIRC.These findings hold significant implications for further research and potential clinical applications.
文摘BACKGROUND Endobronchial metastases(EBMs)are tumours that metastasise from a malignant tumour outside the lungs to the central and subsegmental bronchi,and are visible under a bronchofibrescope.Most EBMs are formed by direct invasion or metastasis of intrathoracic malignant tumours,such as lung cancer,oesophageal cancer or mediastinum tumours.Renal cell carcinoma(RCC),accounting for 2%to 3%of all tumours,is a common malignant tumour of the urinary system.Renal clear cell carcinoma(RCCC)constitutes the predominant pathological subtype of RCC,comprising approximately 70%to 80%of all RCC cases.RCCC can spread and metastasise through arterial,venous and lymphatic circulation to almost all organs of the body.Moreover,lung,bone,liver,brain and local recurrence are the most common metastatic neoplasms of RCCC.However,EBM from RCCC has a low complication rate and is often misdiagnosed as primary lung cancer.CASE SUMMARY A 71-year-old male patient who had undergone radical left nephrectomy 7 years prior due to RCCC was referred to our hospital due to a 1-mo history of productive cough.The results of an enhanced chest CT scan indicated the presence of a soft tissue nodule in the upper lobe of the left lung,and flexible bronchoscopy revealed a hypervascular lesion in the bronchus of the left lung's superior lobe.Therefore,the patient underwent thoracoscopic left superior lobe wedge resection,and pathology confirmed EBM from the RCCC.CONCLUSION EBM from RCCC has a low incidence and no characteristic clinical manifestations in the early stage.If a bronchial tumour is found in a patient with RCCC,the possibility of bronchial metastatic cancer should be considered.
文摘AIM:To clarify the therapeutic strategies and prognosis factors of primary clear cell carcinoma of the liver(PCCCL) . METHODS:The clinical pathological data of 64 patients with PCCCL treated with hepatectomy in our hospital from January 2000 to January 2006 were analyzed retrospectively.The patients were divided into two groups to make treatment analysis:curative resection only(n=40) ;and curative resection and postoperative chemotherapy with calcium folinate and tegafur(n= 24) .Meanwhile,the PCCCL patients were subdivided into two subgroups on the basis of the proportion of clear cells in the tumor for pathological analysis.There were 36 cases in subgroup A for which the proportion of clear cells was more than 70%,and 28 cases in subgroup B for which the proportion was less or equal to 70%,comparing analysis of median survival time of the counterpart groups.Univariate and multivariate analyses were performed to examine factors that affect-ed clinical prognosis,recurrence and metastasis. RESULTS:Median survival period of the curative surgery group was 38 mo,while the counterpart was 41 mo.Median survival period for group A was 41 mo,while group B was 19 mo.The Kaplan-Meier method showed that capsule formation,preoperative liver function,hepatitis C virus infection,large vascular invasion and multiple tumor occurrences were related to disease-free survival.Cox regression analysis showed that the clear cell ratio,capsule formation,preoperative liver function and large vascular invasion were independent risk factors for overall survival. CONCLUSION:Postoperative chemotherapy has no obvious effect on survival of patients with PCCCL. Clear cell ratio,capsule formation,preoperative liver function,and vascular invasion were independent risk factors for prognosis.
文摘AIM: To retrospectively analyze the computed tomography (CT) and magnetic resonance imaging (MRI) appearances of primary clear cell carcinoma of the liver (PCCCL) and compare the imaging appearances of PCCCL and common type hepatocellular carcinoma (CHCC) to determine whether any differences exist between the two groups. METHODS: Twenty cases with pathologically proven PCCCL and 127 cases with CHCC in the Second Affiliated Hospital of Sun Yat-sen University were included in this study. CT or MRI images from these patients were retrospectively analyzed. The following imaging findings were reviewed: the presence of liver cirrhosis, tumor size, the enhancement pattern on dynamic contrast scanning, the presence of pseudo capsules, tumor rupture, portal vein thrombosis and lymph node metastasis. RESULTS: Both PCCCL and CHCC were prone to occur in patients with liver cirrhosis, the association rate of liver cirrhosis was 80.0% and 78.7%, respectively (P > 0.05). The mean sizes of PCCCL and CHCC tumors were (7.28 ± 4.25) cm and (6.96 ± 3.98) cm, respectively. Small HCCs were found in 25.0% (5/20) of PCCCL and 19.7% (25/127) of CHCC cases. No significant differences in mean size and ratio of small HCCs were found between the two groups (P = 0.658 and 0.803, respectively). Compared with CHCC patients, PCCCL patients were more prone to form pseudo capsules (49.6% vs 75.0%, P = 0.034). Tumor rupture, typical HCC enhancement patterns and portal vein tumor thrombosis were detected in 15.0% (3/20), 72.2% (13/18) and 20.0% (4/20) of patients with PCCCL and 3.1% (4/127), 83.6% (97/116) and 17.3% (22/127) of patients with CHCC, respectively. There were no significant differences between the two groups (all P > 0.05). No patients with PCCCL and 2.4% (3/127) of patients with CHCC showed signs of lymph node metastasis (P > 0.05). CONCLUSION: The imaging characteristics of PCCCL are similar to those of CHCC and could be useful for differentiating these from other liver tumors (such as hemangioma and hepatic metastases). PCCCLs are more prone than CHCCs to form pseudo capsules.
文摘Objective:To study the correlation between hyaluronic acid(HA),hyaluronic acid synthase(HAS) and human renal clear cell carcinoma(RCCC).Methods:The expression of three HAS isoforms' gene and HA in 93 RCCC tissues,27 nephridial tissues by the side of RCCC from two hospitals were measured with Real-Time RT-PCR、Western Blot and immunohistochemical methods and analyzed.Results:All RCCC and adjacent normal tissues expressed three HASs' mRNA protein;at the mRNA level,both RCCC and adjacent normal tissues,expressed more HAS3 than HAS1 or HAS2,their differences were statistically significant(all P values 0.05);but,at the protein level,all HAS isoforms presented the equivalent expression.Compared with the adjacent non-neoplastic kidney tissues,the expression of all HAS isoforms' mRNA in RCCC tissues were increased evidently and their differences were significant(all P values 0.0001);but at the protein level,only the expression of HAS3 increased evidently(P=0.022).In all adjacent normal tissues,more than 80% renal tubular cells strongly expressed HA,however,only the minority RCCC cases(16/93) presented weakly positive HA staining in few cancer nests(5%-30%),the difference were significant(P0.0001).In RCCC tissues subgrouped according to clinical stage,pathological grade,lymphatic metastasis or not and distant metastasis or not,the HASs' mRNA protein differential expression all had no statistical significance(all P values 0.05).Conclusion:Different from other malignancy,HA and HASs(except for HAS3) may not play important roles in the biological progress of human RCCC.
文摘BACKGROUND Hyalinizing clear cell carcinoma(HCCC)is an uncommon tumor that originates in the salivary glands.This neoplasia constitutes less than 1%of minor salivary gland tumors.CASE SUMMARY A 67-year-old female visited the maxillofacial surgery department owing to a smooth,slightly yellowish protruding mass on the left side of the floor of the mouth,at the level of the molars;the tumor mass had a soft consistency on palpation and did not adhere to deep planes.The microscopical analysis of the excisional biopsy showed that the lesion was composed of sheets and cords of clear cells separated by thick eosinophilic bands of hyaline collagen.Normal glandular tissue was absent,periodic acid-Schiff with and without diastase stains,and immunohistochemical reactions were performed to confirm the diagnosis.This is the second case reported in the literature of HCCC arising in the floor of the mouth.CONCLUSION HCCC is a rare salivary gland tumor that has not been studied extensively.Its diagnosis is usually challenging,because clinically,it can be confused with a benign neoplasm.
基金funded by the National Science and Technology Major Project for Major New Drug Innovation and Development(2017ZX09302010).
文摘The chemokine ligand 13-chemokine receptor 5(CXCL13-CXCR5)axis has been characterized as a critical tumor-promoting signaling pathway in the tumor microenvironment(TME)in multiple types of solid tumors.In this study,we analyzed the expression profile of CXCL13 in kidney clear cell carcinoma(KIRC)and its correlation with tumor-infiltrating immune cells(TIICs).A monoclonal antibody against CXCL13 with high affinity and purity was generated in our lab for western blot and immunohistochemistry(IHC).Bioinformatic analysis was performed based on bulk-seq data from the Cancer Genome Atlas(TCGA)-KIRC and single-cell RNA-seq data from scRNASeqDB and PanglaoDB.Results showed that high CXCL13 expression in TME was associated with shorter progression-free survival(PFS),disease-specific survival(DSS),and overall survival(OS).KIRC cell lines,as well as several other cancer cell lines,had negative CXCL13 expression.IHC staining from the Human Protein Atlas(HPA)and our tissue array indicated that CXCL13 might be mainly expressed by TIICs,but not KIRC tumor cells.CXCL13 expression was strongly and positively correlated withγδT cell abundance in TME.Besides,γδT cell infiltration was associated with poor survival of KIRC.Methylation 450k array data showed that CXCL13 promoter hypomethylation was common in TIICs.The methylation level of cg16361705 within the CXCL13 promoter might play an important role in modulating CXCL13 transcription.In conclusion,our study revealed that CXCL13 expression andγδT cell infiltration in TME is associated with unfavorable survival of KIRC.TIICs,most possiblyγδT cells,are the dominant source of CXCL13 in KIRC TME.
基金Supported by the National Natural Science Foundation of China,No.81803160.
文摘BACKGROUND Renal clear cell carcinoma(RCC)is a malignant tumor of the genitourinary system with a predilection for males.The most common metastatic sites are the lung,liver,lymph nodes,contralateral kidney or adrenal gland,however,skin metastasis has only been seen in 1.0%-3.3%of cases.The most common site of skin metastasis is the scalp,and metastasis to the nasal ala region is rare.CASE SUMMARY A 55-year-old man with clear cell carcinoma of the left kidney was treated with pembrolizumab and axitinib for half a year after surgery and was found to have a red mass on his right nasal ala for 3 mo.The skin lesion of the patient grew rapidly to the size of 2.0 cm×2.0 cm×1.2 cm after discontinuation of targeted drug therapy due to the coronavirus disease 2019 epidemic.The patient was finally diagnosed with skin metastasis of RCC in our hospital.The patient refused to undergo surgical resection and the tumor shrank rapidly after resuming target therapy for 2 wk.CONCLUSION It is rare for an RCC to metastasize to the skin of the nasal ala region.The tumor size change of this patient before and after treatment with targeted drugs shows the effectiveness of combination therapy for skin metastasis.
文摘BACKGROUND To investigate the clinicopathological features of endometrial clear cell carcinoma that has invaded the right oviduct with a cooccurring ipsilateral oviduct adenomatoid tumor.CASE SUMMARY A case of endometrial clear cell carcinoma invading the right oviduct with a cooccurring ipsilateral oviduct adenomatoid tumor was collected and analyzed using pathomorphology and immunohistochemistry.Endometrial clear cell carcinoma cells were distributed in a solid nest,papillary,shoe nail-like,and glandular tube-like distribution.There was infiltrative growth,and tumor cells had clear cytoplasm and obvious nuclear heteromorphism.The cancer tissue was necrotic and mitotic.The cancer tissue invaded the right oviduct.The ipsilateral oviduct also had an adenomatoid tumor.The adenomatoid tumor was arranged in microcapsules lined with flat or cubic cells that were surrounded by smooth muscle tissue.The adenomatoid tumor cells were round in shape.CONCLUSION Clear cell carcinoma of the endometrium can invade the oviduct and occur simultaneously with tubal adenomatoid tumors.Upon pathological diagnosis,one should pay close attention to distinguishing whether an endometrial clear cell carcinoma is invading the oviduct or whether it is accompanied by an adenomatoid tumor of the oviduct.Immunohistochemistry is helpful to differentiate these two disease entities.Endometrial clear cell carcinomas express Napsin-A and P16 and are negative for estrogen receptor and progesterone receptor.The presence of endometrial clear cell carcinoma does not affect the expression of CK and calretinin in adenomatoid tumors.
文摘Medullary sponge kidney(MSK)is a characteristic renal malformation,with a relatively low incidence.Radiologically,identification of MSK is sometimes ambiguous when compared to a renal mass.Here,we report a novel renal clear cell carcinoma in MSK,and discuss our approach to treatment.We recommended that a preoperative biopsy should be performed,followed by a comprehensive discussion regarding the appropriate perioperative preparations and careful surgical techniques that should be performed for this complex disease.
文摘Clear cell carcinoma (CCC) of the uterine cervix is rare, and its etiology is unclear, except for reports of prenatal diethylstilbestrol (DES) exposure. In this case report of a 78-year-old postmenopausal Japanese woman with pelvic endometriosis, cervical CCC presented as a deep interstitial tumor, strongly suggesting the patient suffered from cervical endometriosis for a long time. A </span><span style="font-family:Verdana;">cystic lesion without solid components was detected in the uterine cervix.</span><span style="font-family:Verdana;"> Although the patient had regular gynecological examinations every 6 months, she presented 5 years later with a complaint of watery vaginal discharge. Ul</span><span style="font-family:Verdana;">trasonography and magnetic resonance imaging (MRI) detected a uterine</span><span style="font-family:Verdana;"> cervical cystic mass with a solid component. Although no malignancy was confirmed preoperatively, surgery was performed under a high suspicion of cervical cancer. Intraoperative pathology revealed CCC in a solid tumor, so debulking surgery, including lymphadenectomy, was done. Endometrial tissue was found adjacent to the tumor, strongly suggesting the tumor arose from cervical endometriosis. Because endometriosis in ectopic sites carries a risk of </span><span style="font-family:Verdana;">carcinogenesis, as is the case in ovarian endometriosis, it may be recom</span><span style="font-family:Verdana;">mended that a cervical cystic lesion with pelvic endometriosis should be followed up regularly for the early detection of uterine cancer.
文摘Primary clear cell carcinoma of the nasopharynx is a rare and locally invasive minor salivary gland neoplasm,only two cases have been reported yet in the literature.Now a 57-year man,with primary nasopharyngeal clear carcinoma,received radiotherapy and chemotherapy.After treatment,the mass of nasopharynx visibly reduced.Follow-up two months and repeated MRI,CT,abdominal B-ultrasonograpy,electronic nasopharyngoscopy,no tumor recurrence or metastasis.
文摘Primary clear cell carcinoma of the breast is a rare tumor with different morphological characteristics compared to ordinary breast carcinomas. The clear cell morphology of the neoplastic population in these tumors has been ascribed to the presence of intracellular lipid, mucin or glycogen, or to myoepithelaial, apocrine, or neuroendocrine differentiation. We describe 2 cases of glycogen-rich clear cell carcinoma of the breast as follows.
文摘This report documents a rare case of complete spontaneous regression of clear cell carcinoma of the endometrium. An elderly woman with paranoid schizophrenia was admitted to the hospital because of vaginal bleeding. Diagnostic curetting and biopsy were performed and she was diagnosed with clear cell carcinoma of endometrium. Anti-tumour therapy was not possible because of her poor psychiatric status. 13 months later the woman died of a natural cause and at autopsy the endometrial tumour could no longer be identified. Myocardial infarction, aggravated by poor functional status of organism due to sepsis, was concluded to be the cause of death.
文摘Background: Ovarian clear cell carcinoma (CCC) is often diagnosed at stage I. However, because of the poor prognosis of recurrent cases, even for stage Ia CCC, treatment strategies such as expansion of fertility-sparing treatment and omission of adjuvant chemotherapy have been carefully discussed in recent years. We previously reported the possibility of the maximum standardized uptake value (SUVmax) as a biomarker of CCC prognosis prediction at all stages. In this study, we confirmed differences in SUVmax within stage I CCC and considered treatment strategies. Methods: We selected all 31 patients with ovarian CCC stage I who underwent fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) before treatment between 2006 and 2013 at our institution. This retrospective study was based on their medical records. Results: Clinical tumor stage was Ia in 13 patients, and Ic in 18 (Ic (b) in 11, and Ic (1) + Ic (2) in seven). There were no differences in serum CA125 level, maximum tumor diameter or mural nodules. Median SUVmax was significantly higher in stage Ic (5.87) than stage Ia (3.08) cases (P = 0.02). Progression-free survival was longer in the low SUVmax group than the high SUVmax group (P = 0.08). Conclusions: SUVmax for primary lesions in CCC was significantly higher in stage Ic than stage Ia. As SUVmax represents a prognostic factor in stage I CCC, these findings may suggest SUVmax as an indicator for the application of fertility-sparing surgery and omission of adjuvant chemotherapy for stage Ia CCC.
文摘Background:Tumor heterogeneity is closely related to the occurrence,progression and recurrence of renal clear cell carcinoma(ccRCC),making early diagnosis and effective treatment difficult.DNA methylation is an important regulator of gene expression and can affect tumor heterogeneity.Methods:In this study,we investigated the prognostic value of subtypes based on DNA methylation status in 506 ccRCC samples with paired clinical data from the TCGA database.Differences in DNA methylation levels were associated with differences in T,N and M categories,age,stage and prognosis.Finally,the samples were divided into the training group and the testing group according to 450K and 27K.Univariate and multivariate Cox regression analysis was used to construct the prediction model in the training group,and the model was verified and evaluated in the testing group.Results:By univariate Cox regression analysis,21,122 methylation sites and 6,775 CpG sites were identified as potential DNA methylation biomarkers for overall survival of ccRCC patients(P<0.05).3,050 CpG sites independently associated with prognosis were identified with T,N,M,stage and age as covariables.Consensus cluster of 3,050 potential prognostic methylation sites was used to identify different DNA methylation subsets of ccRCC for prognostic purposes.We performed functional enrichment analysis on these 3,640 genes and identified 75 significantly enriched pathways(P<0.05).We then researched the expression of methylated genes in subgroups.Verifing with the training set,suggesting that DNA methylation levels generally reflect the expression of these genes.Conclusion:Based on TCGA database and a series of bioinformatics methods,We identified prognostic specific methylation sites and established prognostic prediction models for ccRCC patients.This model helps to identify novel biomarkers,precision drug targets and disease molecular subtypes in patients with ccRCC.Therefore,this model may be useful in predicting the prognosis,clinical diagnosis and management of patients with different epigenetic subtypes of ccRCC.
文摘Objective To explore the diagnosis and treatment features of tuberous sclerosis complex associated renal cell carcinoma. Methods A 22-year-old boy with a childhood history of epilepsy and mental retardation pres-
基金supported by grants from the National Science and Technology Support Project (Grant No. 2015BAI12B12)the National Natural Science Foundation of China (Grant No. 81401887)+1 种基金the National Natural Science Foundation of China (Grant No. 81470293)the Tianjin Natural Science Foundation (Grant No. 14JCQNJC11500)
文摘Objective: Memory stem T cells(Tscm) have attracted attention because of their enhanced self-renewal, multipotent capacity, and anti-tumor capacities. However, little is known about Tscm in patients with renal clear cell carcinoma(RCC) and the role of Wnt signaling in these cells. We evaluated Tscm from RCC patients concerning their activation of Wnt signaling in vitro and explored the mechanism of preferential survival.Methods: Flow cytometry identified surface markers and cytokines produced from accumulated Tscm in the presence of the glycogen synthase kinase beta inhibitor TWS119. Apoptosis was evaluated after induction using tumor necrosis factor-alpha.Immunofluorescence and Western blot analyses were used to investigate the activation of the nuclear factor-kappa B(NF-КB)pathway.Results: RCC patients had a similar percentage of CD4^+ and CD8^+ Tscm as healthy donors. Activation of Wnt signaling by TWS119 resulted in the accumulation of Tscm in activated T cells, but reversal of differentiated T cells to Tscm was not achieved.Preferential survival of Tscm was associated with increased anti-apoptotic ability mediated downstream of the NF-КB activation pathway.Conclusions: The finding that Tscm can accumulate by Wnt signaling in vitro in blood from RCC patients will help in devising new cancer therapy strategies of Tscm-based adoptive immunotherapy, such as dendritic cell-stimulated Tscm, and T cell receptor or chimeric antigen receptor-engineered Tscm.
文摘We report the case of a 67-year-old female who presented with a large renal mass. Gross examination of the nephrectomy specimen demonstrated a 6-cm renal mass that invaded into the renal sinus and perinephric fat. Histologic examination revealed two distinct tumor types. The first type was a conventional(clear cell) renal cell carcinoma that was of low nuclear grade and comprised the minority of the overall tumor. The second type was a high-grade collecting duct carcinoma with glandular/tubular differentiation and composed the majority of the tumor. Immunohistochemical studies demonstrated distinctive patterns of the two tumor types, thus confirming two distinct lineages. Five months postoperatively, the patient developed metastasis to the lungs and right hilar lymph node region. A fine needle aspiration of a lung nodule demonstrated a metastatic, poorly differentiated carcinoma, similar to the collecting duct carcinoma component in the kidney. Collision tumors of the kidney are rare with fewer than 10 cases reported in the literature. Our report further expands the spectrum of this rare phenomenon.