economical-efficient-protocol-for-isolating-culturing-bone-marrow

Economical and Efficient Protocol for Isolating and Culturing Bone Marrow-derived Dendritic Cells from Mice

The demand for dendritic cells (DCs) is gradually increasing as immunology research advances. However, DCs are rare in all tissues. The traditional method ...

The Second Hospital of Tianjin Medical University

Genetic polymorphisms in glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) genes have been widely reported and considered to have a significant effect on prostate cancer (PCa) risk, but the results are inconsistent. To evaluate the impact of the GSTM1 and GSTT1 polymorphism on PCa risk, we conducted a comprehensive meta-analysis based on 18 eligible studies. A total of 18 studies, including 7,119 subjects for GSTM1 and 6,454 subjects for GSTT1 between 1999 and 2012 were identified through researching MEDLINE, PubMed, Web of Science, EMBASE, Chinese National Knowledge Infrastructure database, and Chinese Biomedical Literature database. A meta-analysis was performed to obtain summary-estimated odd ratios and 95% confidence intervals of GSTM1 and GSTT1 polymorphisms for PCa, with attention to study quality and publication bias. Overall, there is a significant association between GSTM1 (odds ratio (OR) = 1.407, 95% confidence intervals (95% CI) = 1.147-1.727, I(2) = 73.2%, P = 0.001) genotypes and PCa susceptibility. Significant associations were also observed in subgroups of Caucasian populations (OR = 1.262, 95% CI = 1.055-1.511, I(2) = 48.7%, P = 0.011) and Asian populations (OR = 1.776, 95% CI = 1.134-2.781, I(2) = 83.4%, P = 0.012). However, no significant association was found (OR = 1.776, 95% CI = 1.134-2.781, P = 0.243) in African-American populations when stratified by ethnicity. While, there was no significant association seen between GSTT1 (OR = 1.003, 95% CI = 0.823-1.298, I(2) = 68.8%, P = 0.778) genotypes and PCa risk. However, no significant associations were observed in subgroups of Caucasian populations (OR = 1.086, 95% CI = 0.801-1.471, I(2) = 72.1%, P = 0.597) and Asian populations (OR = 0.961, 95% CI = 0.644-1.434, I(2) = 73.0%, P = 0.846), and similar result was found among African-American populations (OR = 0.802, 95% CI = 0.194-3.321, P = 0.761) when stratified by ethnicity. Our results suggest that the GSTM1 gene polymorphism contributes to PCa susceptibility, while GSTT1 gene polymorphism is not associated with PCa in our study.

Association between glutathione S-transferases M1 and T1 gene polymorphisms and prostate cancer risk: a systematic review and meta-analysis.

We present a rare case of silent giant pheochromocytoma with leukemoid reaction that has not been reported before. The patient was a 61-year-old woman who complained of progressive weight loss for 3 months. Preoperatively the urine vanillylmandelic acid was 105.54 mg/24 hours. White blood cell count was 56.9 × 10/L. Abdominal ultrasound and computed tomography revealed a mass measuring 18 × 11 cm in the left adrenal area. The patient underwent adrenal gland neoplasm resection. Postoperative histopathologic evaluation confirmed the diagnosis of pheochromocytoma. The leukocyte dropped to normal gradually in 10 days after the operation. Giant pheochromocytoma with leukemoid reaction was very rare. Resection is the only curative treatment.

Giant Pheochromocytoma With Leukemoid Reaction: A Case Report.

The prognostic value of C-reactive protein (CRP) in metastatic renal cell carcinoma (RCC) patients receiving tyrosine kinase inhibitors (TKIs) has been investigated in previous studies; however, the results remain inconclusive. This study investigated the prognostic value of pretreatment CRP in patients with metastatic RCC treated with TKIs.

C-reactive protein is a predictor of prognosis in renal cell carcinoma patients receiving tyrosine kinase inhibitors: A meta-analysis.

Previous studies have investigated the prognostic significance of Ki-67/MIB-1 expression in renal cell carcinoma (RCC), however, the reports are controversial and inconsistent. This study aimed to investigate Ki-67/MIB-1 expression in RCC and its correlation with prognosis and clinicopathological features.

Prognostic and clinicopathological value of Ki-67/MIB-1 expression in renal cell carcinoma: a meta-analysis based on 4579 individuals.

The prognostic value of p53 expression in renal cell carcinoma (RCC) had been investigated in previous studies; however, the results remain inconsistent. This study was performed to investigate the prognostic and clinicopathological significance of p53 protein expression in RCC.

Prognostic and clinicopathological value of p53 expression in renal cell carcinoma: a meta-analysis.

The prognostic significance of PD-L1 in renal cell carcinoma (RCC) had been investigated in previous studies; however, the results remain controversial. The primary aim of this meta-analysis was to investigate the prognostic and clinicopathological significance of the PD-L1 expression in patients with RCC. Relevant literature was identified form PubMed, Embase, Web of Science and Cochrane library, which compared the prognostic significance between PD-L1 expression and RCC. Hazard ratios (HRs) for survival outcomes and odds ratios (ORs) for clinical parameters associated with PD-L1 were extracted from eligible studies. Heterogeneity was assessed using the I value. The fixed-effects model was used if there was no evidence of heterogeneity; otherwise, the random-effects model was used. Publication bias was evaluated using Begg's funnel plots and Egger's regression test. A total of 1863 patients from ten eligible studies were analyzed. The results showed that PD-L1 expression is associated with poor overall survival in clear cell RCC (ccRCC) (HR = 2.76, 95%CI: 2.25-3.38, I = 14.4%, P < 0.001) and non-clear cell RCC (non-ccRCC) (HR = 2.77, 95%CI: 1.62-4.72, I = 28.8%, P < 0.001). In addition, PD-L1 expression was found to be significantly associated with primary tumor stage (OR = 1.76, 95%CI: 1.39-2.23; I = 56.3%), regional lymph node involvement (OR = 2.10, 95%CI: 1.48-2.98; I = 14.9%), distant metastases (OR = 2.69, 95%CI: 2.05-3.54; I = 0.0%), nuclear grade (OR = 1.72, 95%CI: 1.32-2.23; I = 79.4%) and histologic tumor necrosis (OR = 2.25, 95%CI: 1.59-3.18; I = 66.1%) in patients with RCC. The outcome stability was confirmed by sensitivity analysis. Both the Begg's funnel plot test (P = 0.276) and the Egger's (P = 0.388) verified that there was no publication bias within the included studies. This study suggests that PD-L1 expression is correlated with poor prognosis and advanced clinicopathological features in RCC patients.

Prognostic and clinicopathological significance of PD-L1 in patients with renal cell carcinoma: a meta-analysis based on 1863 individuals.

Castration resistant prostate cancer (CRPC) is a stage of relapse that arises after various forms of androgen ablation therapy (ADT) and causes significant morbidity and mortality. However, the mechanism underlying progression to CRPC remains poorly understood. Here, we report that YAP1, which is negatively regulated by AR, influences prostate cancer (PCa) cell self-renewal and CRPC development. Specifically, we found that AR directly regulates the methylation of YAP1 gene promoter via the formation of a complex with Polycomb group protein EZH2 and DNMT3a. In normal conditions, AR recruits EZH2 and DNMT3a to YAP1 promoter, thereby promoting DNA methylation and the repression of YAP1 gene transcription. Following ADT treatment or when AR activity is antagonized by Bicalutamide or Enzalutamide, YAP1 gene expression is switched on. In turn, YAP1 promotes SOX2 and Nanog expression and the de-differentiation of PCa cells to stem/progenitor-like cells (PCSC), which potentially contribute to disease recurrence. Finally, the knock down of YAP1 expression or the inhibition of YAP1 function by Verteporfin in TRAMP prostate cancer mice significantly suppresses tumor recurrence following castration. In conclusion, our data reveals that AR suppresses YAP1 gene expression through a novel epigenetic mechanism, which is critical for PCa cells self-renewal and the development of CRPC.

YAP1 regulates prostate cancer stem cell-like characteristics to promote castration resistant growth.

The prognostic value of plated-lymphocyte ratio (PLR) in multiple malignancies had been investigated in previous studies; however, its prognostic value in renal cell carcinoma (RCC) remains controversial. This study was performed to assess the prognostic value of preoperative PLR in RCC patients.

Platelet-lymphocyte ratio acts as an independent predictor of prognosis in patients with renal cell carcinoma.

The prognostic value of PBRM1 expression in renal cell carcinoma (RCC) had been investigated in previous studies; however, the results remain inconclusive. We investigated the prognostic value and clinicopathological significance of PBRM1 protein expression in RCC.

Prognostic and clinicopathological value of PBRM1 expression in renal cell carcinoma.

The prognostic value of neutrophil-lymphocyte ratio (NLR) in patients with castration-resistant prostate cancer (CRPC) had been investigated in previous studies; however, the results remain inconsistent. This study was aimed to investigate the prognostic value of NLR in CRPC patients.

Neutrophil-lymphocyte ratio is a predictor of prognosis in patients with castration-resistant prostate cancer: a meta-analysis.

[This corrects the article DOI: 10.18632/oncotarget.21971.].

Correction: Prognostic and clinicopathological value of p53 expression in renal cell carcinoma: a meta-analysis.

Chemotherapy may be a valuable treatment option as neoadjuvant treatment for locally advanced penile cancer according to some previous studies, but the rarity of the sample and the Lack of large-scale clinical trials hampered the attempt to establish a solid evidence base for its routine use. The purpose of this study was to evaluate the efficacy of the neoadjuvant chemotherapy combined with a ITP regimen including docetaxel, cisplatin and ifosfamide for treating advanced penile cancer patients.

Neoadjuvant docetaxel, cisplatin and ifosfamide (ITP) combination chemotherapy for treating penile squamous cell carcinoma patients with terminal lymph node metastasis.

In recent years, there has been an increase in the incidence of small renal masses (SRMs) and nephrectomy was the standard management of this disease in the past. Currently, the use of active surveillance has been recommended as an alternative option in the case of some patients with SRMs due to its heterogenicity. However, limited studies focused on the regarding risk stratification. Therefore, in the current study, we developed a nomogram for the purpose of predicting the presence of high-grade SRMs on the basis of the patient information provided (clinical information, hematological indicators, and CT imaging data).

Development and validation of CT imaging-based preoperative nomogram in the prediction of unfavorable high-grade small renal masses.

(1) Background: There are currently limited treatments for castration-resistant prostate cancer. Immunotherapy involving Sipuleucel-T has increasingly drawn attention for prostate cancer management. BCG plays a vital role in treating bladder cancer, mainly by inducing immune activation, but is rarely used for prostate cancer. (2) Methods: The TCGA database, PCR, and Western blotting were used to analyze the expression of STEAP1 in mouse and human tissues. Then, we constructed a fusion protein vaccine with  Ag85B and three repeated octapeptide epitopes of a six-transmembrane epithelial antigen of the prostate 1 (STEAP1), Ag85B-3×STEAP1. The uptake of the fusion protein vaccine by DCs was evaluated by confocal microscopy, and DC markers were detected using flow cytometry after incubation with the fusion protein. The immune response against prostate cancer was evaluated by the LDH assay and xenografts in vitro and in vivo. Then, the tumor microenvironment was determined using IHC and ELISA. In addition, the epitope was mutated using CRISPR-Cas9 to illustrate that the fusion protein elicited immunization against STEAP1. (3) Results: The TCGA database analysis, PCR, and Western blotting showed that STEAP1 was highly expressed in human and murine prostate cancer. After the uptake of the purified fusion protein vaccine by DCs, CD11c, CD80, CD86, and MHC II were upregulated and triggered a cytotoxic T lymphocyte (CTL) response against TRAMP-C1 and RM1 cells in vitro. Furthermore, the fusion protein vaccine inhibited tumor growth and improved the tumor microenvironment in vivo, with more CD3 cells and fewer FOXP3 cells in the tumor. Serum IFN-γ and IL-2 were significantly higher than in the control group, while IL-4 expression was lower, indicating that the fusion protein vaccine activated Th1 immunity. The immune response against prostate cancer was greatly suppressed when the antigen targets were knocked out using CRISPR-Cas9. (4) Conclusion: In summary, our results provide the first evidence that a vaccine based on a fusion protein consisting of Ag85B and a prostate cancer octapeptide epitope with complete Freund's adjuvant (CFA), triggers a robust immune response and inhibits tumor growth in murine prostate cancer.

Fusion Protein Vaccine Based on Ag85B and STEAP1 Induces a Protective Immune Response against Prostate Cancer.

 It has been reported that thymidine kinase 1 (TK1) was up-regulated in multiple malignancies and participated in the regulation of tumor malignant behavior. However, its specific role in prostate cancer (PCa) remains unclear.  TK1 expression in PCa patients and cell lines was identified via crossover analysis of the public datasets. A series of  experiments and  models was applied to investigate the function of TK1 in PCa. Functional enrichment analyses were further conducted to explore the underlying mechanism. Additionally, TISIDB was applied to explore the correlation between TK1 expression and tumor-infiltrating lymphocytes, immune subtypes, and immune regulatory factors.  TK1 expression was significantly up-regulated in PCa patients and cell lines. TK1 ablation inhibited tumor cell proliferation and migration potential, and  experiments showed that TK1 inactivation can significantly restrain tumor growth. Functional enrichment analysis revealed TK1-related hub genes (AURKB, CCNB2, CDC20, CDCA5, CDK1, CENPA, CENPM, KIF2C, NDC80, NUF2, PLK1, SKA1, SPC25, ZWINT), and found that TK1 was closely involved in the regulation of cell cycle. Moreover, elevated mRNA expression of TK1 was related with higher Gleason score, higher clinical stage, higher pathological stage, higher lymph node stage, shorter overall survival, and DFS in PCa patients. Particularly, TK1 represented attenuated expression in C3 PCa and was related with infiltration of CD4, CD8 T cells, and dendritic cells as well as immunomodulator expression.  Our study indicates that TK1 is a prognostic predictor correlated with poor outcomes of PCa patients, and for the first time represented that TK1 can promote the progression of PCa. Therefore, TK1 may be a potential diagnostic and prognostic biomarker, as well as a therapeutic target for PCa.

Article	Year
Association between glutathione S-transferases M1 and T1 gene polymorphisms and prostate cancer risk: a systematic review and meta-analysis. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine\| PubMed ID: 23888321	2014
Giant Pheochromocytoma With Leukemoid Reaction: A Case Report. Urology\| PubMed ID: 27720771	2017
C-reactive protein is a predictor of prognosis in renal cell carcinoma patients receiving tyrosine kinase inhibitors: A meta-analysis. Clinica chimica acta; international journal of clinical chemistry\| PubMed ID: 29080691	2017
Prognostic and clinicopathological value of Ki-67/MIB-1 expression in renal cell carcinoma: a meta-analysis based on 4579 individuals. Cancer management and research\| PubMed ID: 29200888	2017
Prognostic and clinicopathological value of p53 expression in renal cell carcinoma: a meta-analysis. Oncotarget\| PubMed ID: 29254251	2017
Prognostic and clinicopathological significance of PD-L1 in patients with renal cell carcinoma: a meta-analysis based on 1863 individuals. Clinical and experimental medicine\| PubMed ID: 29362922	2018
YAP1 regulates prostate cancer stem cell-like characteristics to promote castration resistant growth. Oncotarget\| PubMed ID: 29383141	2017
Platelet-lymphocyte ratio acts as an independent predictor of prognosis in patients with renal cell carcinoma. Clinica chimica acta; international journal of clinical chemistry\| PubMed ID: 29462592	2018
Prognostic and clinicopathological value of PBRM1 expression in renal cell carcinoma. Clinica chimica acta; international journal of clinical chemistry\| PubMed ID: 30006290	2018
Neutrophil-lymphocyte ratio is a predictor of prognosis in patients with castration-resistant prostate cancer: a meta-analysis. Cancer management and research\| PubMed ID: 30271208	2018
Correction: Prognostic and clinicopathological value of p53 expression in renal cell carcinoma: a meta-analysis. Oncotarget\| PubMed ID: 30555638	2018
Neoadjuvant docetaxel, cisplatin and ifosfamide (ITP) combination chemotherapy for treating penile squamous cell carcinoma patients with terminal lymph node metastasis. BMC cancer\| PubMed ID: 31238987	2019
Development and validation of CT imaging-based preoperative nomogram in the prediction of unfavorable high-grade small renal masses. Cancer management and research\| PubMed ID: 31576175	2019
Fusion Protein Vaccine Based on Ag85B and STEAP1 Induces a Protective Immune Response against Prostate Cancer. Vaccines\| PubMed ID: 34358202	2021
Assessing the Potential Prognostic and Immunological Role of TK1 in Prostate Cancer. Frontiers in genetics\| PubMed ID: 35559045	2022

Zhun Wang

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