[A multicenter study on childhood Hodgkin lymphoma treated with HL-2013 regimen in China].

Objective: To evaluate the efficacy of the Hodgkin lymphoma (HL)-2013 regimen in the treatment of children with HL, and to investigate the prognostic factors of childhood HL. Methods: Clinical data of 145 children (aged ≤18 years) with newly diagnosed HL, treated with HL-2013 regimen in 8 tertiary referral centers for childhood cancer from August 2011 to April 2021 were analyzed retrospectively. All the diagnosis were confirmed by histopathological morphology and immunohistochemical examination. The clinical characteristics and treatment outcomes were summarized, and the patients were divided into different groups according to clinical characteristics. Kaplan-Meier method was used for survival analysis, and the comparison of survival rates between groups was performed with Log-rank test. Results: Of the 145 cases, there were 115 males and 30 females, the age at diagnosis was 7.9 (5.8, 10.6) years. Cervical lymph node enlargement (114 cases, 78.6%) was the common symptom of the disease, and 57 patients (39.3%) were accompanied by large masses. The most common pathological classification was mixed cell type (93 cases, 64.1%). According to the Ann Arbor staging system, there were 9 cases of stage Ⅰ, 62 cases of stage Ⅱ, 45 cases of stage Ⅲ, 29 cases of stage Ⅳ. According to the risk stratification: there were 14 cases of low-risk group, 76 cases of medium-risk group and 55 cases of high-risk group. Of all patients, 68 cases (46.9%) achieved an early complete remission (CR) after 2 courses of chemotherapy, and the CR rate was 93.8% (136/145) after first-line treatment. Disease recurrence or progression occurred in 22 cases (15.2%). Of all patients, 125 cases survived, 6 cases died and 14 cases were lost to follow-up. Among the survived cases, 123 cases were continuously at CR state,and the follow-up time was 55 (40, 76) months. The 5-year overall survival (OS) and event free survival (EFS) rates were (95.3±1.9)% and (84.2±3.0)% for the entire group, respectively. 5-year OS and EFS rates for patients with stage Ⅲ-Ⅳ were both lower than those for patients with stage Ⅰ-Ⅱ (χ2=6.28 and 7.58, both P<0.05), the 5-year OS and EFS rates for patients in high-risk group were both lower than those for patients in low-risk and medium-risk group (χ2=10.93, 7.79, both P<0.05). The 5-year OS rates for the patient with early CR and without early CR were 100.0% and (90.9±3.6)% (χ2=5.77, P=0.016). EFS rates for the patient with early CR (68 cases) and without early CR (77 cases) were (93.8±3.0)% and (75.8±5.0)% (χ2=8.78, P=0.003). Conclusions: HL-2013 regimen is significantly effective in the treatment of pediatric HL. However, the patients in high-risk group and those without early CR are prone to disease recurrence or progression. Stage Ⅲ-Ⅳ and without early CR were associated with worse prognosis.

[Correlation between temporomandibular joint osteoarthrosis and coronoid process].

Objective: To investigate the morphological characteristics of coracoid process in different stages of temporomandibular joint osteoarthrosis (TMJOA), and to provide theoretical data for clinical and anatomic study. Methods: A total of 290 patients who were diagnosed with TMJOA in the Department of Temporomandibular Joint, Kunming Medical University School and Hospital of Stomatology from January 2015 to February 2021 were collected, including 69 males and 221 females, with an average age of 35.1±13.7 years (16-69 years old), 64 cases of unilateral lesions (64 sides), and 226 cases of bilateral lesions (452 sides). According to the TMJOA X-ray staging standard put forward by Ma Xuchen in 2005, the affected joints were divided into stage I (227 sides), stage Ⅱ (38 sides), stage Ⅲ (164 sides) and stage Ⅳ (87 sides). Twenty-six patients without clinical and imaging manifestations of temporomandibular disorders in the Department of Radiology, Kunming Medical University School and Hospital of Stomatology from October 2020 to June 2021 were selected as the control group, including 8 males and 18 females. The average age was (34.3±13.9) years (17-60 years). The dicom data of each group were imported into SimplantPro11.04 software to measure the height of coracoid process, anteversion angle and the ratio of coracoid vertex to mandibular corner to condylar vertex to mandibular angle. R 3.6.1 was used to analyze the difference of the morphological characteristics of coracoid process between in the affected side of TMJOA and in the both sides of the control group, in the healthy side and the affected side of unilateral patients and in different stages of TMJOA. Results: The height of the coracoid process [(16.26±2.81 mm)], the ratio of the coracoid process vertex-mandibular angle point and the condyle vertex-mandibular angle point distance [0.96(0.92,1.01)] on the affected side of TMJOA were significantly higher than those in the control group [(15.31±3.03)mm;0.95(0.89、0.99)] (t=2.18, P=0.033; t=2.87, P=0.004). There was no significant difference between the ante-version angle and the control group (t=-1.37, P=0.176). The ratio of the distance between the apex of the coracoid process and the apex of the mandibular angle to the apex of the condyle and the angle of the mandible in the affected side of unilateral patients was significantly greater than that in the healthy side (t=-3.46, P=0.001). There was no significant difference in coracoid height, coracoid anteversion angle and the healthy side (t=-1.85, P=0.069; t=-0.06, P=0.955) in different periods. The intra-group analysis showed that there was no significant difference in the height of the coracoid process in different stages (F=0.37, P=0.774). There was no significant difference in the ante-version angle of the coracoid process: stage I, stage Ⅱ, and stage Ⅲ (P>0.008), but all were significantly smaller than stage Ⅳ (PⅠ-Ⅳ<0.001, PⅡ-Ⅳ=0.009, PⅢ-Ⅳ<0.001). The ratio of the distance between coracoid apex-mandibular angle and condyle apex-mandibular angle: there was no significant difference in stage I, stage Ⅱ, and stage Ⅲ (P>0.008), and stage I and stage Ⅲ were significantly smaller than stage Ⅳ (P<0.001). Conclusions: The coracoid height and the ratio of the coracoid apex-mandibular angle to the condyle apex-mandibular angle distance on the TMJOA side were significantly greater than those without temporomandibular joint disorders. The bone deposition was mainly concentrated in the upper and posterior part of the condyle. TMJOA had a certain correlation with the height of the coracoid process.

[Clinical diagnosis and treatment of 27 cases of metanephric adenoma].

The clinical features, imaging features, treatment methods and pathological features of 27 patients with metanephric adenoma were analyzed. It was found that the clinical features and imaging features of metanephric adenoma were difficult to differentiate from renal malignantology. Pathology can be clearly diagnosed and some can be combined with malignant components. Nephron sparing surgery is the first choice, and the prognosis is good, but still need regular follow-up.

[Transcriptome sequencing-based classification and quantification of IKZF1 transcript isoforms in B-cell acute lymphoblastic leukemia].

Objective: To classify and quantify IKZF1 mutant transcripts in B-cell acute lymphoblastic leukemia (B-ALL) by RNA sequencing (RNA-seq) and bioinformatics analysis. Methods: A cohort of 263 B-ALL cases was enrolled at Hebei Yanda Ludaopei Hospital from September 2018 to September 2020. An integrated bioinformatics pipeline was developed to adapt the classification and quantification of IKZF1 transcripts from RNA-seq and was applied to sequencing data of these cases. The IKZF1 mutant transcripts classified by RNA-seq analysis were compared with the qualitative reverse transcription PCR (RT-PCR). Results: IKZF1 mutant transcripts were identified in 53 B-ALL patients by RT-PCR and Sanger sequencing, among which IK6 and IK10 transcripts accounted for 67.9% (36/53) and 28.3% (15/53) respectively. Additionally, 2 patients were double positive for IK6 and IK10. RNA-seq analysis identified 51 patients with IKZF1 mutant transcripts. Compared with the RT-PCR result, the detection sensitivity and specificity of RNA-seq analysis reached 94.3% (50/53) and 99.5% (209/210), respectively. Among the 50 patients with IKZF1 mutant transcripts both in RNA-seq and RT-PCR analysis, the ratio of mutant transcripts to total IKZF1 transcripts in 6 patients was 0.14 (0.11, 0.35), which was significantly lower than that of the other 44 patients [0.88 (0.35, 0.97), Z=-3.945,P<0.001]. IKZF1 mutations mostly occurred in Ph+and Ph-like B-ALL, characterized by abnormal JAK-STAT pathway, and B-ALL with PAX5 translocation. Conclusions: Through the optimized bioinformatics analysis process, RNA-seq data can be used to classify and quantitatively analyze IKZF1 transcripts in B-ALL. Furthermore, the relative expression of mutant IKZF1 transcripts was found to cluster into two groups, and IKZF1 mutation was found often accompanied with PAX5 translocations.

[ABO gene subtypes and gene expression analysis in three cases of hematological malignancies patients].

Objective: To explore the application and discovery of genotyping, gene sequencing, and gene expression analysis in the determination of ABO blood group subtypes and antigen expression abnormalities in hematological malignancies patients. Methods: From June 2019 to May 2020, three clinical cases were found with forward and reverse ABO typing discrepancy or atypical serologic agglutination pattern in the laboratory and blood transfusion department of Hebei Yanda Ludaopei Hospital were selected. Sequence-specific primer PCR (PCR-SSP) and Sanger sequencing of ABO gene coding regions were performed to determine the ABO genotypes, and whole transcriptome sequencing was used to analyze ABO and FUT1 gene expression levels. Results: A 12-year-old female acute lymphoblastic leukemia patient was determined as O.01.02 and BA.04 sub-genotype, corresponding to the serological B(A) subtype, and her ABO gene expression was normal (354.80). A 41-year-old female acute myeloid leukemia patient was determined as A1.02 and B.01 genotype, corresponding to the serological A(1)B phenotype, and her ABO gene expression was significantly reduced (45.70). A 42-year-old male with myelodysplastic syndrome and myelofibrosis was determined as A1.02 and A2.05 sub-genotype, corresponding to the serological A(1) and A(2) phenotype, respectively, and his ABO expression was negative. FUT1 expression was in the normal range in all three cases. The clinical blood product infusion strategy was formulated according to the genotype and the corresponding immunological subtype, and no significant transfusion-related adverse reactions occurred. Conclusion: Blood group sub-genotypes or aberrant gene expression can lead to ambiguities in serological blood group determination in hematological malignancies patients. ABO genotyping and gene expression analysis can help in this scenario and escort blood product infusion safety.

Full-length sequence of the MICA allele, MICA*067, identified in a Chinese individual.

MICA*067 differs from MICA*004:01:01 by a single nucleotide change in exon 3, 374 A>G.

[The impact of KIT and other concomitant gene mutations on the prognoses of patients with core-binding factor acute myeloid leukemia].

Objective: To study the impact of KIT and other concomitant gene mutations on the prognoses of patients with core-binding factor acute myeloid leukemia (CBF-AML). Methods: A total of 104 newly diagnosed patients with CBF-AML in Hebei Yanda Lu Daopei Hospital from January 2014 to February 2018 were analyzed, and high-throughput gene sequencing for the detection of mutations among 58 genes was executed. Also, the clinical features of KIT mutation-positive CBF-AML (KIT+CBF-AML) patients and the effects of other concomitant gene mutations on the prognoses of patients were also analyzed. Results: A total of 56 cases (53.85%) with KIT mutations were found in 104 CBF-AML patients. Among this, KIT D816 mutation was the most common (32 patients), followed by the N822 mutation (17 patients). Patients with KIT+CBF-AML have a higher proportion of bone marrow blasts at the time of diagnoses and are more likely to have sex chromosome loss. Among the 52 patients with KIT+CBF-AML who were followed up, the allogeneic hematopoietic stem cell transplantation (allo-HSCT) group had a higher overall survival rate (OS) than that of the chemotherapy group (88.9% vs 57.1%, χ(2)=6.076, P<0.05). The event-free survival (EFS) and OS of patients with KIT+CBF-AML with FLT3 mutation were both significantly lower than those of the FLT3 mutation-negative group (EFS: 40.0% vs 72.3%, χ(2)=6.557, P<0.05; OS: 60.0% vs 87.2%, χ(2)=8.305, P<0.05). The OS of the patient with TET2 mutation was lower than that of the TET2 mutation-negative group (50.0% vs 87.5%, χ(2)=4.130, P<0.05). Conclusion: Patients with KIT+CBF-AML with concomitant gene mutations, especially FLT3 and TET2, have poor prognoses, which can be improved by allo-HSCT.

Genetic variant spectrum in 265 Chinese patients with hemophagocytic lymphohistiocytosis: Molecular analyses of PRF1, UNC13D, STX11, STXBP2, SH2D1A, and XIAP.

Hemophagocytic lymphohistiocytosis (HLH) is a rare life-threatening hyperinflammatory disease. This study aimed to investigate the frequencies and distributions of inherited variants in PRF1, UNC13D, STX11, STXBP2, SH2D1A, and XIAP genes in Chinese patients with HLH. A total of 265 patients diagnosed with HLH from January, 2010 to December, 2016 were recruited and analyzed for the 6 genes. Genetic variants were observed in 87 (32.83%) patients. 36 (13.58%) exhibited variants in UNC13D, 18 (6.79%) exhibited PRF1 variants, 10 (3.77%) had variants in XIAP, 9 (3.40%) exhibited variants in STXBP2, 6 (2.26%) carried variants in SH2D1A, 1 (0.38%) had STX11 variant, and 7 (2.64%) exhibited digenic variants. Monoallelic variants were the most common, which accounted for 49.43% of all cases with variants. All variants were confirmed to be germline-derived. The present study describes a distinct variant spectrum in Chinese patients with HLH, whereby UNC13D is the most frequently mutated gene with missense variants that are the most common molecular defects. The variant profile of Chinese HLH patients is quite different from that of Western cohorts but similar to that of Korean patients, yet showing its own uniqueness. This racial difference shows the role of genetic background in the occurrence of HLH.

SEGMENTATION OF ORGANS AT RISK IN THORACIC CT IMAGES USING A SHARPMASK ARCHITECTURE AND CONDITIONAL RANDOM FIELDS.

Cancer is one of the leading causes of death worldwide. Radiotherapy is a standard treatment for this condition and the first step of the radiotherapy process is to identify the target volumes to be targeted and the healthy organs at risk (OAR) to be protected. Unlike previous methods for automatic segmentation of OAR that typically use local information and individually segment each OAR, in this paper, we propose a deep learning framework for the joint segmentation of OAR in CT images of the thorax, specifically the heart, esophagus, trachea and the aorta. Making use of Fully Convolutional Networks (FCN), we present several extensions that improve the performance, including a new architecture that allows to use low level features with high level information, effectively combining local and global information for improving the localization accuracy. Finally, by using Conditional Random Fields (specifically the CRF as Recurrent Neural Network model), we are able to account for relationships between the organs to further improve the segmentation results. Experiments demonstrate competitive performance on a dataset of 30 CT scans.

Cotransplantation of bone marrow-derived mesenchymal stem cells in haploidentical hematopoietic stem cell transplantation in patients with severe aplastic anemia: an interim summary for a multicenter phase II trial results.

This corrects the article DOI: 10.1038/bmt.2016.347.

Cotransplantation of bone marrow-derived mesenchymal stem cells in haploidentical hematopoietic stem cell transplantation in patients with severe aplastic anemia: an interim summary for a multicenter phase II trial results.

Haploidentical hematopoietic stem cell transplantation (haplo-HSCT) for severe aplastic anemia (SAA) is mainly limited by the high incidence of graft failure and GvHD. Mesenchymal stem cells (MSCs) have been shown to support hematopoiesis in vivo and to display potent immunosuppressive effects to prevent or treat GvHD after HSCT. In a multicenter phase II trial, we developed an approach with co-transplantation of MSCs in patients undergoing haplo-HSCT. Forty-four patients with SAA were included. The conditioning regimen included busulfan, cyclophosphamide and thymoglobulin (ATG). The recipients received cyclosporin A (CsA), mycophenolate mofetil and short-term methotrexate for GvHD prophylaxis. Three out of 44 patients, who died early before hematopoietic engraftment, were not assessed. Evaluable patients (97.6%; 40/41) achieved hematopoietic reconstitution and sustained full donor chimerism. The median time for myeloid engraftment was 12 days (range 8-21 days) and for platelet engraftment was 19 days (range 8-154 days). The incidence was 29.3% for grade II-IV acute GvHD and 14.6% for chronic GvHD. The overall survival was 77.3% with a median 12-month (range 0.9-30.8) follow-up for surviving patients. These data suggest that co-transplantation of MSCs could reduce the risk of graft failure and severe GvHD in haplo-HSCT for SAA.

A novel HLA-A*24 allele, HLA-A*24:325, identified in a Chinese individual.

HLA-A*24:325 differs from A*24:02:01:01 by two nucleotide substitutions at position 411 and 412.

Hepatitis C virus core protein interacts with Snail and histone deacetylases to promote the metastasis of hepatocellular carcinoma.

Downregulation of E-cadherin by the transcriptional repressor Snail is associated with acquisition of metastatic potential. Although hepatitis C virus (HCV) core protein has been implicated in hepatocarcinogenesis, it is unclear whether Snail is involved in HCV core-induced dysregulation of E-cadherin. Herein, we investigated the mechanism by which HCV core induces E-cadherin repression and the role of Snail in HCV core-mediated invasiveness and metastasis. We found that HCV infection, especially HCV core expression, effectively induced the epithelial-mesenchymal transition (EMT) in hepatoma cells by repressing E-cadherin. HCV core interacted with Snail and enhanced its binding to the E-box in the promoter region of E-cadherin, leading to decreased E-cadherin promoter activity. We found that HCV core, Snail, and the histone deacetylases HDAC1/HDAC2 formed a co-repressor complex at the E-cadherin promoter. Moreover, HCV core was shown to stabilize Snail through activation of the PI3K/Akt/GSK3ß pathway. Silencing Snail expression restored E-cadherin expression and inhibited HCV core-promoted tumor growth and distant lung metastasis in vivo. Collectively, these results demonstrated that HCV core induced EMT by interacting with the transcriptional repressor complex Snail/HDACs at the E-cadherin promoter, which led to E-cadherin repression and increased invasiveness of hepatoma cells. These findings increase understanding of factors regulating metastasis in hepatoma and may ultimately lead to the development of novel treatment strategies for HCV-associated hepatocellular carcinoma.

Nicotine elevates sperm motility and induces Pfn1 promoter hypomethylation in mouse testis.

Many studies have addressed the hazardous role of cigarette smoking on male fertility, but the exact molecular mechanisms involved in the impairments caused by nicotine remain unclear. To evaluate the detrimental effects of nicotine exposure on spermatogenesis, two-dimensional gel electrophoresis and mass spectrometry analysis were performed to screen and identify differentially expressed proteins from the testes of mice exposed to nicotine daily. Data mining analysis indicated that the 15 identified proteins were mainly involved in actin cytoskeleton regulation and in the tricarboxylic acid cycle, which are related to cell motility. Further investigation of a central regulatory factor in the cytoskeleton regulation, profilin 1 (PFN1), revealed that nicotine-induced Pfn1 over-expression in mouse testes, specifically in elongated spermatids, by Pfn1 promoter hypomethylation. Interestingly, elevated sperm motility parameters were observed in nicotine-treated mice. We assume that nicotine-induced PFN1 over-expression in mouse spermatids may promote actin polymerization and ultimately enhance sperm motility.

HLA-A*11:188: a new allele identified by sequence-based typing in a Chinese blood donor.

A novel allele HLA-A*11:188 differs from HLA-A*11:01:01 by a single mutation at position 439 in exon 3.

Identification of the novel HLA-C*03:240 allele.

HLA-C*03:240 differs from HLA-C*03:42 by a single nucleotide substitution that results in a missense mutation Tyr 99 Cys (TAT to TGT).

Comparison of long-term and short-term administration of itraconazole for primary antifungal prophylaxis in recipients of allogeneic hematopoietic stem cell transplantation: a multicenter, randomized, open-label trial.

BACKGROUND: The optimal agents and duration of primary antifungal prophylaxis in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain a matter of discussion. OBJECTIVE: Our objective was to compare the efficacy and safety of long-term and short-term administration of itraconazole (ITCZ) for primary antifungal prophylaxis in allo-HSCT recipients. METHODS: This multicenter, randomized, open-label pilot study was performed in 4 transplant centers in China. Recipients of allo-HSCT without a history of invasive fungal disease (IFD) were randomly assigned to the long-term or the short-term arm. Randomization was carried out by a center computer system. Intravenous ITCZ was given to the patients in both study arms with a loading dose of 400 mg/day for 2 days followed by 200 mg/day until day +14 or when the white blood cell count was >1.0 × 10(9) /L, and then switched to oral ITCZ solution; prophylaxis was continued until day +30 post transplantation in the short-term arm or until day +90 in the long-term arm. The trough serum concentrations of ITCZ also were measured. The primary study endpoint was the incidence of IFD (proven, probable, and possible) within day +90 post transplantation. RESULTS: A total of 128 recipients were enrolled in this study; 59 of them were randomized to the long-term arm and 62 were randomized to the short-term arm, forming the modified intent-to-treat (mITT) set. The incidence of IFD within day +90, the primary endpoint, was not significantly different between the 2 arms for the mITT set (6.78% in the long-term arm vs. 6.45% in the short-term arm, P = 0.94), or for the per-protocol set (6.90% in the long-term arm vs. 6.67% in the short-term arm, P = 0.96). From day +30 to day +90, the incidence of IFD was 0% and 6.45%, respectively, in the patients with long-term and short-term prophylaxis for the mITT set (P = 0.11). The mean trough serum concentrations of ITCZ was maintained at >500 ng/mL throughout administration. The incidences of withdrawal because of drug-related adverse events in patients with long-term and short-term prophylaxis were 6.78% and 0%, respectively (P = 0.05). CONCLUSIONS: Long-term and short-term administration of ITCZ both seemed effective in preventing IFD in recipients of allo-HSCT. Further study with large sample size should be performed to evaluate this result. ITCZ shows the same pharmacokinetics in recipients of allo-HSCT as in non-recipients.

Hepatitis C virus core protein epigenetically silences SFRP1 and enhances HCC aggressiveness by inducing epithelial-mesenchymal transition.

Hepatocellular carcinoma (HCC) is one of the most deadly cancers. Aberrant oncogenic activation of the Wnt/ß-catenin signaling pathway contributes to hepatocellular carcinogenesis. Various epigenetic modifications of the Wnt antagonist secreted frizzled-related protein (SFRP) family have been implicated in regulating Wnt signaling. Here, we report that Hepatitis C virus (HCV) core protein downregulates SFRP1 expression when it is expressed in Huh7 and HepG2 cells. SFRP1 expression can be effectively restored by using either a DNA methylation inhibitor alone or in combination with a histone deacetylase inhibitor. DNA methylation analysis of the SFRP1 promoter revealed that cytosine-phosphate-guanine (CpG) islands close to the transcriptional start site (TSS) in the SFRP1 promoter were hypermethylated in core-expressing Huh7 cells, suggesting that HCV core protein may downregulate SFRP1 expression by inducing hypermethylation of the SFRP1 promoter. Chromatin immunoprecipitation revealed that HCV core protein markedly increased the expression level and binding of DNA methyltransferase-1 (Dnmt1) and histone deacetylase-1 (HDAC1) to the TSS of the SFRP1 promoter region, resulting in repression of acetyl-histone H3-binding capacity to SFRP1 promoter and the eventual epigenetic silencing of SFRP1 expression. Furthermore, the core protein-promoted cell proliferation, migration and invasiveness were effectively abrogated either by Dnmt1 knockdown or restoration of SFRP1 expression in hepatoma cells. Dnmt1 knockdown or SFRP1 overexpression also inhibited HCV core-induced epithelial-mesenchymal transition (EMT) and significantly decreased the expression levels of activated ß-catenin and Wnt/ß-catenin target genes, c-Myc and cyclin D1. We further showed that knockdown of Dnmt1 and restoration of SFRP1 inhibited core-induced in vivo tumor growth and aggressiveness in a xenograft HCC model. Taken together, our results strongly suggest that the HCV core-induced epigenetic silencing of SFRP1 may lead to the activation of the Wnt signaling pathway and thus contribute to HCC aggressiveness through induction of EMT.

Radiosensitivity of human prostate cancer cells can be modulated by inhibition of 12-lipoxygenase.

Nearly 30% of prostate cancer (PCa) patients treated with potentially curative doses relapse at the sites of irradiation. How some tumor cells acquire radioresistance is poorly understood. The platelet-type 12-lipoxygenases (12-LOX)-mediated arachidonic acid metabolism is important in PCa progression. Here we show that 12-LOX confers radioresistance upon PCa cells. Treatment with 12-LOX inhibitors baicalein or BMD122 sensitizes PCa cells to radiation, without radiosensitizing normal cells. 12-LOX inhibitors and radiation, when combined, have super additive or synergistic inhibitory effects on the colony formation of both androgen-dependent LNCaP and androgen-independent PC-3 PCa cells. In vivo, the combination therapy significantly reduced tumor growth.