Curcumin induces the expression of NF-κB and Bcl-2/Bax in human renal cell carcinoma cell line ACHN

Objective： To explore the in vitro effects of curcumin on the proliferation and apoptosis of the human renal cell carcinoma cell line ACHN, and to investigate its mechanisms of action. Methods： The human renal cell carcinoma cell line ACHN was treated with different concentrations of curcumin for 24 h. The MTT assay was used to evaluate the cytotoxic effects of curcumin and flow cytometry was utilized to observe and detect the apoptosis of ACHN cells induced by curcumin. The expression levels of Bcl-2, Bax and NF-κBP65 mRNA were evaluated by Reverse Transcription-Polymerase Chain Reaction （RT-PCR）, while the expression of Bcl- 2, Bax, NF-κBP65 and IκB proteins was evaluated by Western blot. Results： The concentrations of curcumin used significantly inhibited the proliferation of ACHN human renal cell carcinoma cells in vitro in a dose and time-dependent manner （Ftime=5.55, P 〈 0.05; Fdose=110.05, P 〈 0.05）. Obvious apoptosis of cells treated with different concentrations of curcumin could be observed by FCM. Compared with the control group, the apoptosis rates of curcumin-treated cells were markedly increased （F=96.35, P 〈 0.05）. Lower dose of curcumin significantly induced the apoptosis of ACHN cells. With intervention of different concentrations of curcumin （0, 10, 20 and 40 μmol/L） for 24 h, the expression levels of Bcl-2 and NF-κBP65 mRNA in ACHN cells were decreased while the expression level of Bax mRNA was increased （P 〈 0.05）, and Bcl-2, and NF-κBP65 protein decreased, while Bax and IκB protein increased compared with those in the untreated group. Conclusion： Curcumin inhibited proliferation and increased apoptosis of the human renal cell carcinoma cell line ACHN. These curcumin effects appear to involve up-regulating IκB, down-regulating NF-κB, and regulating the expression of the apoptosis genes Bcl-2/Bax.

Optimal sequential therapy using tyrosine kinase inhibitors as the first-line treatment in patients with metastatic renal cell carcinoma: A nationwide multicenter study

Objective:The purpose of the study was to identify the best sequence of therapy beginning with a tyrosine kinase inhibitor(TKI)as the first-line therapy for patients with metastatic renal cell carcinoma(mRCC)in terms of overall survival(OS),progression-free survival(PFS),and rates of discontinuation and adverse effects during the treatment period.Methods:This is a retrospective,nationwide multicenter study of patients with mRCC after diagnosis at 10 different tertiary medical centers in Korea from January 1992 to December 2017.We focused on patients at either“favorable”or“intermediate”risk according to the International mRCC Database Consortium criteria,and they were followed up(median 335 days).Finally,a total of 1409 patients were selected as the study population.We generated a Cox proportional hazard model adjusted for covariates,and the different therapy schemes were statistically tested in terms of OS as well as PFS.In addition,frequencies of discontinuation and adverse events were compared among the therapy schemes.Results:Of the primary patterns of treatment sequences(24 sequences),“sunitinib epazopanib”and“sunitinibeeverolimuseimmunotherapy”showed the most beneficial results in both OS and PFS with significantly lower hazards than“sunitinib”,which is the most commonly treated agent in Korea.Considering that the“TKIeTKI”structure showed relatively higher discontinuation rates with higher adverse effects,the overall beneficial sequence would be“sunitinibeeverolimuseimmunotherapy”.Conclusion:Among several sequential therapy starting with TKIs,“sunitinibeeverolimuse immunotherapy”was found to be the best scheme for mRCC patients with“favorable”or“intermediate”risks.

Primary parenchymal squamous cell carcinoma of the kidney:A case report

BACKGROUND Primary squamous cell carcinoma(SCC)of the renal parenchyma is extremely rare,with only nine cases reported.CASE SUMMARY This study reports a 51-year-old man with primary SCC of the renal parenchyma.The patient was admitted with recurrent dull pain and discomfort in the right lumbar region,which had worsened over 2 weeks,accompanied by painful gross hematuria.SCC antigen(SCCA)levels were elevated,and imaging revealed a renal mass with associated calculi.The patient underwent laparoscopic unilateral nephrectomy and lymph node dissection.Postoperative pathology confirmed highly differentiated SCC with necrosis in the right renal parenchyma,with negative renal pelvis and ureter.The pathological stage was Pt3aN1M0.Four months after surgery,the tumor recurred with involvement of the liver,right psoas major muscle,and inferior vena cava.The patient refused chemotherapy and succumbed to the disease 6 months postoperatively due to disease progression.CONCLUSION We report a case of primary SCC of the renal parenchyma,a rare renal malignancy.The clinical symptoms,laboratory tests,and imaging findings are nonspecific,making accurate and timely diagnosis challenging.According to the literature,for patients with renal calculi accompanied by a renal mass,elevated serum SCCA levels,and magnetic resonance imaging showing cystic or cystic-solid masses within the kidney with pseudocapsules and heterogeneous mild enhancement,the possibility of this disease should be considered.

Ipsilateral retroperitoneal papillary renal cell carcinoma 27 years after simple nephrectomy for a renal abscess:A case report

BACKGROUND Cases of severe inflammatory renal disease and renal cell carcinoma(RCC)that occur simultaneously in the same kidney have been occasionally reported.However,extrarenal RCC that does not originate from the native kidney has rarely been reported.To our knowledge,this is the first reported case of RCC developing in the ipsilateral retroperitoneal space after a simple nephrectomy(SN)for inflammatory renal disease.CASE SUMMARY A 63-year-old woman was referred to our hospital following the incidental discovery of a left retroperitoneal mass without specific symptoms.Her medical history revealed a left SN 27 years ago due to a renal abscess.Magnetic resonance imaging of the abdomen revealed three oval masses in the left retroperitoneum.The masses were successfully excised,and subsequent pathology confirmed papillary RCC.After surgery,the patient remained disease-free for 11 years without adjuvant therapy.CONCLUSION Clinicians should be vigilant of RCC in patients with retroperitoneal masses,especially after SN for inflammatory renal disease.

Endobronchial metastasis secondary to renal clear cell carcinoma:A case report

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.

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.

Integrative bioinformatics and in vitro exploration of EVI2A expression:unraveling its immunological and prognostic implications in kidney renal clear cell carcinoma

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.

Low expression of fatty acid oxidation related gene ACADM indicates poor prognosis of renal clear cell carcinoma and is related to tumor immune infltration

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.

Incidental renal cell carcinoma post bilateral nephrectomy in autosomal dominant polycystic kidney disease

BACKGROUND Renal cell carcinoma(RCC)is more common in patients with autosomal dominant polycystic kidney disease(ADPKD)than in the general population.Diagnosing RCC in ADPKD is challenging due to the presence of multiple renal cysts,often leading to delays and difficulties in distinguishing RCC from cyst infection or hemorrhage.A total of 38 kidneys were excised from 19 patients,with a mean age of 56.8 years and an average hemodialysis duration of 84.2 months.Eight patients underwent open nephrectomies,and 11 underwent hand-assisted laparoscopic nephrec-tomies.RCC was detected in 15.8%of kidneys,affecting 21.1%of patients.Two patients had multifocal RCC in both kidneys.All RCC cases were pT1 stage,with the largest lesion averaging 16.5 mm in diameter.The average operative duration was 120 minutes,with intraoperative blood loss averaging 184.2 mL.Five patients required blood transfusions.Postoperative complications occurred in five patients,with a mean hospital stay of 17.1 days.The mean follow-up period was 28.1 months.CONCLUSION The prevalence of RCC is higher in patients with ADPKD with ESRD than in those with ESRD alone.Thus,clinicians should be cautious and implement surveillance programs to monitor the development of RCC in patients with ADPKD,particularly those on dialysis.

Toripalimab in combination with chemotherapy effectively suppresses local recurrence and metastatic sarcomatoid renal cell carcinoma:A case report

BACKGROUND Sarcomatoid renal cell carcinoma(SRCC)is a rare variant of renal cell carcinoma associated with an unfavorable prognosis.The efficacy of conventional chemo-therapy and targeted therapies are limited,whereas the emergence of immune checkpoint inhibitor has introduced new avenues for managing advanced SRCC.CASE SUMMARY A 77-year-old female patient was referred to our hospital following the incidental detection of a right kidney tumor without specific symptoms.The tumor was successfully resected,and subsequent pathological examination confirmed SRCC.She experienced both local recurrence and distant metastasis eight months after the initial laparoscopic resection.Following six cycles of toripalimab combined with pirarubicin chemotherapy,the patient achieved a partial response.Subse-quently,the patient attained an almost-complete continuous response to toripa-limab monotherapy maintenance for an additional six cycles.She has not experienced disease progression for 15 months,and her overall survival has reached 24 months thus far.CONCLUSION Combination therapy with programmed death 1 antibodies and cytotoxic agents may be a recommended first-line treatment approach for SRCC.

Comprehensive assessment of the association between tumorinfiltrating immune cells and the prognosis of renal cell carcinoma

BACKGROUND According to current statistics,renal cancer accounts for 3%of all cancers world-wide.Renal cell carcinoma(RCC)is the most common solid lesion in the kidney and accounts for approximately 90%of all renal malignancies.Increasing evi-dence has shown an association between immune infiltration in RCC and clinical outcomes.To discover possible targets for the immune system,we investigated the link between tumor-infiltrating immune cells(TIICs)and the prognosis of RCC.AIM To investigate the effects of 22 TIICs on the prognosis of RCC patients and iden-tify potential therapeutic targets for RCC immunotherapy.METHODS The CIBERSORT algorithm partitioned the 22 TIICs from the Cancer Genome Atlas cohort into proportions.Cox regression analysis was employed to evaluate the impact of 22 TIICs on the probability of developing RCC.A predictive model for immunological risk was developed by analyzing the statistical relationship between the subpopulations of TIICs and survival outcomes.Furthermore,multi-variate Cox regression analysis was used to investigate independent factors for the prognostic prediction of RCC.A value of P<0.05 was regarded as statistically significant.RESULTS Compared to normal tissues,RCC tissues exhibited a distinct infiltration of im-mune cells.An immune risk score model was established and univariate Cox regression analysis revealed a significant association between four immune cell types and the survival risk connected to RCC.High-risk individuals were correlated to poorer outcomes according to the Kaplan-Meier survival curve(P=1E-05).The immunological risk score model was demonstrated to be a dependable predictor of survival risk(area under the curve=0.747)via the receiver operating characteristic curve.According to multivariate Cox regression analysis,the immune risk score model independently predicted RCC patients'prognosis(hazard ratio=1.550,95%CI:1.342–1.791;P<0.001).Finally,we established a nomogram that accurately and comprehensively forecast the survival of patients with RCC.CONCLUSION TIICs play various roles in RCC prognosis.The immunological risk score is an independent predictor of poor survival in kidney cancer cases.

Eosinophilic solid and cystic renal cell carcinoma with aggressive behavior:Two case reports

BACKGROUND Eosinophilic solid and cystic(ESC)renal cell carcinoma(RCC),a unique and emerging subtype of RCC,has an indolent nature;in some rare instances,it may exhibit metastatic potential.Current cases are inadequate to precisely predict the clinical outcome of ESC RCC and determine treatment choices.CASE SUMMARY Herein,we report two patients with ESC RCC.Patient 1 was a young woman with classical pathological characteristics.Patient 2 was a 52-year-old man with multifocal metastases,involving the pulmonary hilar and mediastinal lymph nodes,liver,brain,mesosternum,vertebra,rib,femur,and symphysis pubis.Awareness of ESC RCC,along with its characteristic architecture and immunophenotype,would contribute to making a definitive diagnosis,even on core biopsy samples.CONCLUSION The discovery of ESC RCC molecular signatures may provide new therapeutic strategies in the future.

Advances in treatment strategies for non–clear cell renal cell carcinoma

Renal cell carcinoma is the sixth most commonly diagnosed cancer in men and the tenth in women,with clear cell renal cell carcinoma accounting for nearly 75%of cases.The remaining 25%consists of non–clear cell renal cell carcinoma,a diverse and less prevalent group.Although current treatments for clear cell types are well-defined,progress in treating non–clear cell renal cell carcinoma has been limited owing to its heterogeneity and rarity,relying primarily on findings from small-scale phase Ⅱ clinical trials.This review examined recent advancements in the treatment of non–clear cell renal cell carcinoma,particularly in the areas of immunotherapy and targeted therapy.

Network pharmacology and molecular docking analysis reveal insights into the molecular mechanism of Gualou Qumai Wan in clear cell renal cell carcinoma

Background:To initially clarify the potential therapeutic targets and pharmacological mechanism regarding Gualou Qumai Wan(GQW),a kind of traditional Chinese medicine(TCM),in clear cell renal cell carcinoma(ccRCC)by virtue of the network pharmacology analysis and molecular docking analysis.Methods:The screening of bioactive components and targets of GQW was based on the Traditional Chinese Medicine System Pharmacology(TCMSP)and the UniProt platform served for standardizing their targets.Online Mendelian Inheritance in Man(OMIM),PharmGkb,TTD,DrugBank and GeneCards databases were searched to collect the disease targets of ccRCC.Cytoscape assisted in constructing herb-compound-target(H-C-T)networks.The STRING database was searched for constructing the target protein-protein interaction(PPI)networks,while the R programming language served for analyzing GO functional terms and the KEGG pathways related to potential targets.Analyses of core genes related to survival and tumor microenvironment(TME)were conducted respectively based on the GEPIA2 database and TIMER 2.0 database.Human Protein Atlas(HPA)and The Cancer Genome Atlas(TCGA)helped to obtain core genes’protein expression as well as transcriptome expression level.Autodock Vina software validated the molecular docking regarding GQW components and pivotal targets.Results:The constructed H-C-T networks mainly had 33 compounds and 65 targets.A topological analysis of the PPI network identified that ESR1,AKT1,HIF1A,PTGS2,TP53 and VEGFA serve as core targets in the way GQW affects ccRCC.According to the GO and KEGG pathway enrichment analyses,the effects of GQW are mediated by genes related to hypoxia and oxidative stress as well as the Chemical carcinogenesis-receptor activation and PI3K-Akt signaling pathways.AKT1 shows a close relation to the recruitment of various immune cells and can remarkably affect disease prognosis according to reports.Molecular docking and molecular dynamics simulations showed that diosgenin has higher affinity with core targets.Conclusion:The study makes a comprehensive explanation of the biological activity,potential targets,as well as molecular mechanism regarding GQW against ccRCC,which promisingly assists in revealing the action mechanism of TCM formulae in disease treatment and the respective and scientific basis.

Comparison of efficacy, safety, and quality of life between sorafenib and sunitinib as first.line therapy for Chinese patients with metastatic renal cell carcinoma

Background: Sorafenib and sunitinib are widely used as first-line targeted therapy for metastatic renal cell carcinoma(mRCC) in China.This study aimed to compare the efficacy, safety, and quality of life(QoL) in Chinese mRCC patients treated with sorafenib and sunitinib as first-line therapy.Methods: Clinical data of patients with mRCC who received sorafenib(400 mg twice daily; 4 weeks) or sunitinib(50 mg twice daily; on a schedule of 4 weeks on treatment followed by 2 weeks off) were retrieved. Primary outcomes were overall survival(OS), progression-free survival(PFS), adverse events(AEs), and QoL(SF-36 scores), and secondary outcomes were associations of clinical characteristics with QoL.Results: Medical records of 184 patients(110 in the sorafenib group and 74 in the sunitinib group) were reviewed.PFS and OS were comparable between the sorafenib and sunitinib groups(both P > 0.05).The occurrence rates of leukocytopenia, thrombocytopenia, and hypothyroidism were higher in the sunitinib group(36.5% vs. 10.9%,P< 0.001; 40.5% vs. 10.9%, P < 0.001; 17.6% vs. 3.6%, P = 0.001), and that of diarrhea was higher in the sorafenib group(62.7% vs. 35.2%, P < 0.001). There was no significant difference in SF-36 scores between the two groups. Multivariate analysis indicated that role-physical and bodily pain scores were associated with the occurrence rate of grade 3 or 4 AEs(P = 0.017 and 0.005).Conclusions: Sorafenib has comparable efficacy and lower toxicity profile than sunitinib as first-line therapy for mRCC. Both agents showed no significant impact on QoL of patients.

Inhibition of Proliferation Induced by Cyclin D1 Gene Silence in Human Renal Carcinoma ACHN Cells

Objective： To confirm feasibility of Cyclin D1 gene as a new target for cancer gene therapy and to verify the effectiveness of shRNA expression vector-mediated gene silencing. Methods： A RNA interference DNA template targeting Cyclin D1 gene was designed and synthesized. By ligation, the fragment was inserted into Pgenesil-1-U6 to constract the recombinant plasmid Pgenesil-shRNA-Cyclin D1. The identified recombinant plasmid was transfected into ACHN cells with lipofactamine. Cyclin D1 mRNA and protein expression was analyzed by RT-PCR and western-blotting. MTT method was used for observing cell proliferation and drawing growth curve. The cell cycle and ratios of apoptotic cell were assessed by flow cytometric detection. The ability of invasion of cell migration was detected by Transwell chamber invasive models. Results： The plasmid was constructed successfully. After interference, The expression rate of Cyclin D1 mRNA decreased to 0.10±0.04 in Cyclin D1-shRNA（experimental） group and were significantly lower than Pgenesil-NC （negative） group （0.92±0.03） and ACHN （blank control） group（0.94±0.04）（P0.05）. As well, the expression rate of Cyclin D1 protein was decreased evidently in experimental group. The results of flow cytometric detection showed that, including early and late apoptotic cells, the apoptotic ratio of experimental group increased to （37.26±0.60）% significantly, while, the negative group and blank control group were only （4.62±0.40）% and （5.95±1.20）%, respectively. The cell growth curves indicated that the proliferation of experimental group cells was inhibited significantly（P0.05） and Transwell results suggested that the abilities of invasion cells transfected with Pgenesil–CyclinD1-shRNA decreased conspicuously（P0.05）. Conclusion： The shRNA can inhibit Cyclin D1 expression, specifically and persistently. The down-regulation of Cyclin D1 expression can inhibit the proliferation and induce the apoptosis of renal cell adenocarcinoma cell line ACHN.

Translating new data to the daily practice in second line treatment of renal cell carcinoma:The role of tumor growth rate

The therapeutic options for patients with metastatic renal cell carcinoma(mRCC) have completely changed during the last ten years. With the sequential use of targeted therapies, median overall survival has increased in daily practice and now it is not uncommon to see patients surviving kidney cancer for more than four to five years. Once treatment fails with the first line targeted therapy, head to head comparisons have shown that cabozantinib, nivolumab and the combination of lenvatinib plus everolimus are more effective than everolimus alone and that axitinib is more active than sorafenib. Unfortunately, it is very unlikely that we will ever have prospective data comparing the activity of axitinib, cabozantinib, lenvatinib or nivolumab. It is frustrating to observe the lack of biomarkers that we have in this field, thus there is no firm recommendation about the optimal sequence of treatment in the second line. In the absence of reliable biomarkers, there are several clinical endpoints that can help physicians to make decisions for an individual patient, such as the tumor burden, the expected response rate and the time to achieve the response to each agent, the prior response to the agent administered, the toxicity profile of the different compounds and patient preference. Here, we propose the introduction of the tumor-growth rate(TGR) during first-line treatment as a new tool to be used to select the second line strategy in m RCC. The rapidness of TGR before the onset of the treatment reflects the variability between patients in terms of tumor growth kinetics and it could be a surrogate marker of tumor aggressiveness that may guide treatment decisions.

Effects of Peptide Nucleic Acids against Ki-67 Gene on the Proliferation and Apoptosis of Human Renal Carcinoma Cell Line

To investigate the effects of anti-sense peptide nucleic acids （PNAs） targeting Ki-67 gene on modulation of the proliferation and apoptosis of human renal carcinoma cell lines, human renal carcinoma cell line 786-0 cells were treated with anti-sense PNAs at different concentrations （1.0 μmol/L, 2.0 μmol/L, 10.0 μmol/L）. The Ki-67 expression of 786-0 cells was detected by immunohistochemical technique and Western blot method respectively. The proliferation of 786-0 cells was studied by cell growth curves and ^3H-thymidine incorporation. The apoptosis of 786-0 cells was detected by TUNEL assay. The control groups were treated with anti-sense oligonucleotide （ASODNs） targeting Ki-67 gene. Our results showed that the Ki-67 expression of 786-0 cells treated with anti-sense PNAs （16.9±0.7） was significantly inhibited as compared with that of the control groups （28.6±0.4） （P〈0.01）. The Ki-67 protein rate of 786-0 cells treated with anti-sense PNAs （42.1 ±2.2） was significantly reduced when compared with that of the control groups （83.6± 1.4） （P〈0.01）. Proliferation of 786-0 cells treated with anti-sense PNAs （20.7 ± 1.5） was significantly inhibited as compared with that of the control groups （58.6± 1.4） （P〈0.01）. The apoptosis rate of 786-0 cells treated with anti-sense PNAs （28.7 ± 2.3） was significantly increased higher compared with that of the control groups （13.8 ±1.0） （P〈0.01）. From these finds we are led to conclude that anti-sense PNAs targeting Ki-67 gene have stronger effects on the inhibition of the proliferation and induction of apoptosis of human renal carcinoma cells than ASODNs targeting Ki-67 gene. The strategies using anti-sense PNAs targeting Ki-67 gene may be a promising approach for the treatment of renal cell carcinoma.

Effects of Arsenic Trioxide on Human Renal Cell Carcinoma Lines in Vitro

Objective: To observe the effects of arsenic trioxide (As2O3) on human renal cell carcinoma (RCC) lines in vitro and to explore its possible molecular mechanisms. Methods: The microculture tetrazoli-um (MTT) assay was used to determine the anti-proliferative effects of As2O3 on human RCC lines. Flow cy-tometry was performed to investigate the effects of As2O3 on cell cycle and cell apoptosis. The reverse tran-scription-polymerase chain reaction (RT-PCR) was conducted to detect mRNA expression of Bcl-2, Bax, p53 and c-myc. Results: As2O3 inhibited the growth of RCC lines in vitro in a concentration-dependent manner. At the concentrations of 0.5, 1.0, 2.0 and 4.0μmol/L, the inhibition rates of As2O3 on RCC-WCS cells were 27.60%, 30.09%, 41.03% and 50.77%, respectively. Compared with untreated RCC-WCS, there was significant difference at each concentration (P<0.01). As2O3 induced a G1 phase arrest in RCC-LSL cells, but a G2/M phase arrest in RCC-WCS and RCC-SHK. As2O3 induced cell apoptosis in these cell lines. The mRNA level of p53 and c-myc decreased, but no detectable changes of Bcl-2 and Bax were observed after As2O3 treatmen. Conclusion: As2O3 in therapeutic concentrations inhibited the in vitro growth of RCC lines via cell cycle arrest and apoptosis. One of its possible mechanisms was down-regulation of p53 and c-myc. Our results suggest that As2O3 is probably a new candidate agent for the treatment of human renal carcinoma.

Efficacy and Safety of Axitinib as First-Line Therapy in Japanese Patients with Metastatic Renal Cell Carcinoma

Previous study reported that patients treated with axitinib as second-line therapy had longer median progression-free survival than those treated with sorafenib for metastatic renal cell carcinoma (mRCC). In this study, we reviewed our experience of axitinib as a first-line therapy for mRCC in Japanese patients, focusing on its efficacy and safety. We retrospectively assessed 26 patients treated with axitinib as a first-line therapy for mRCC from July 2010 to July 2014 at Chiba Cancer Center and Kinki University Hospital. Observation period was 24.6 ± 18.3 months. The objective response rate was 50.0%, and the median progression-free survival was 27.5 months. Overall survival was not estimable. Common grade 3 adverse events were hypertension in 19 patients and proteinuria in 5 patients. Axitinib demonstrated significant efficacy as a first-line therapy in Japanese patients with mRCC. Careful monitoring and management of the adverse effects may help to control its toxicities.