Antioxidative stress protein SRXN1 can be used as a radiotherapy prognostic marker for prostate cancer.

PURPOSE: To explore the mechanisms of radiotherapy resistance and search for prognostic biomarkers for prostate cancer. METHODS: The GSE192817 and TCGA PRAD datasets were selected and downloaded from the GEO and UCSC Xena databases. Differential expression and functional annotation analyses were applied to 52 tumour cell samples from GSE192817. Then, the ssGSEA or GSVA algorithms were applied to quantitatively score the biological functional activity of samples in the GSE192817 and TCGA PRAD datasets, combined with specific gene sets collected from the Molecular Signatures Database (MSigDB). Subsequently, the Wilcoxon rank-sum test was used to compare the differences in ssGSEA or GSVA scores among cell types or PRAD patients. Moreover, radiotherapy resistance-associated gene screening was performed on DU145 and PC3 cells (prostate cancer cells), and survival analysis was used to evaluate the efficacy of these genes for predicting the prognosis of PRAD patients. RESULTS: A total of 114 genes that were differentially expressed in more than two different cancer cell types and associated with either sham surgery or radiotherapy treatment (X-ray or photon irradiation) were detected in cancer cells from GSE192817. Comparison of DNA damage-related ssGSEA scores between sham surgery and radiotherapy treatment in prostate cancer cells (DU145 and PC3) showed that photon irradiation was potentially more effective than X-ray treatment. In the TCGA PRAD dataset, patients treated with radiotherapy had much higher "GOBP_CELLULAR_RESPONSE_TO_DNA_DAMAGE_STIMULUS", "GOBP_G2_DNA_DAMAGE_CHECKPOINT" and "GOBP_INTRA_S_DNA_DAMAGE_CHECKPOINT" GSVA scores, and the Wilcoxon rank-sum test p values were 0.0005, 0.0062 and 0.0800, respectively. Furthermore, SRXN1 was upregulated in DU145 cells (resistant to X-ray irradiation compared to PC3 cells) after radiotherapy treatment, and low SRXN1 expression in patients was beneficial to radiotherapy outcomes. The log-rank test p value for PFS was 0.0072. CONCLUSIONS: Radiotherapy can damage DNA and induce oxidative stress to kill tumour cells. In this study, we found that SRXN1, as an antioxidative stress gene, plays an important role in radiotherapy for prostate cancer treatment, and this gene is also a potential biomarker for predicting the prognosis of patients treated with radiotherapy.

Efficacy and safety of LY01005 versus goserelin implant in Chinese patients with prostate cancer: A multicenter, randomized, open-label, phase III, non-inferiority trial.

BACKGROUND: LY01005 (Goserelin acetate sustained-release microsphere injection) is a modified gonadotropin-releasing hormone (GnRH) agonist injected monthly. This phase III trial study aimed to evaluated the efficacy and safety of LY01005 in Chinese patients with prostate cancer. METHODS: We conducted a randomized controlled, open-label, non-inferiority trial across 49 sites in China. This study included 290 patients with prostate cancer who received either LY01005 or goserelin implants every 28 days for three injections. The primary efficacy endpoints were the percentage of patients with testosterone suppression ≤50 ng/dL at day 29 and the cumulative probability of testosterone ≤50 ng/dL from day 29 to 85. Non-inferiority was prespecified at a margin of -10%. Secondary endpoints included significant castration (≤20 ng/dL), testosterone surge within 72 h following repeated dosing, and changes in luteinizing hormone, follicle-stimulating hormone, and prostate specific antigen levels. RESULTS: On day 29, in the LY01005 and goserelin implant groups, testosterone concentrations fell below medical-castration levels in 99.3% (142/143) and 100% (140/140) of patients, respectively, with a difference of -0.7% (95% confidence interval [CI], -3.9% to 2.0%) between the two groups. The cumulative probabilities of maintaining castration from days 29 to 85 were 99.3% and 97.8%, respectively, with a between-group difference of 1.5% (95% CI, -1.3% to 4.4%). Both results met the criterion for non-inferiority. Secondary endpoints were similar between groups. Both treatments were well-tolerated. LY01005 was associated with fewer injection-site reactions than the goserelin implant (0% vs . 1.4% [2/145]). CONCLUSION: LY01005 is as effective as goserelin implants in reducing testosterone to castration levels, with a similar safety profile. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04563936.

Single-cell sequencing reveals MYC targeting gene MAD2L1 is associated with prostate cancer bone metastasis tumor dormancy.

BACKGROUND: Among malignant tumors, bone metastasis is frequently associated with prostate cancer which is seen in about 80% of patients. During cancer treatments, some tumor cells switch to a "dormant mode" to help tumor cells avoid attack from the immune system and anti-tumor therapies. In this dormant mode, tumor cells can be resuscitated, causing cancer to reoccur. The generally accepted explanation for this phenomenon is that the tumor cells have spread to the bone marrow before treatment and are dormant in the bone marrow. However, the key mechanism for inducing and maintaining the dormancy of these prostate cancer disseminated tumor cells in the bone marrow is still unclear. Therefore, studying the dormancy mechanism of tumor cells in bone metastasis is of great significance for the treatment and the prevention of recurrence of prostate cancer. METHODS: We obtained single-cell RNA-seq data of tumors from mouse models of prostate cancer bone metastasis mouse model numbered (GSE147150) from the GEO database, and obtained RNA-seq expression data and clinical information from The Cancer Genome Atlas Program (TCGA) of prostate cancer patients from the USCS Xena database. Screening of differential genes and annotation of GO functions were performed separately. Subsequently, the screened differential genes were compared and analyzed with 50 classic Hallmark signaling pathways, and the prognosis analysis of prostate cancer patients in TCGA data was performed to discover the key genes of the dormant mechanism of tumor cells in bone metastasis, and obtain new biomarkers that can be used to predict the prognosis of patients. RESULTS: A total of 378 differentially expressed genes were screened, of which 293 were significantly up-regulated and 85 were significantly down-regulated. Among them, the up-regulated genes were mainly related to the immune response, and the down-regulated genes were mainly related to the cell cycle. Through GSVA (Gene set variation analysis), it is found that there are differences in a total of 3 signal pathways: COMPLEMENT, MYC_TARGETS_V1 and MYC_TARGETS_V2. By comparing and analyzing the significantly down-regulated genes in dormant tumor cells with MYC_TARGETS_V1, MYC_TARGETS_V2, three significantly down-regulated genes were obtained: Ccna2, Mad2L1 and Plk1. CONCLUSION: In summary, our findings indicate that the MYC targeting gene Mad2L1 is potentially related to the dormancy mechanism of prostate cancer. At the same time, Mad2L1, a gene associated with dormant prostate cancer cells, may be used as a biomarker for prognostic survival.

Rare case of brucellosis misdiagnosed as prostate carcinoma with lumbar vertebra metastasis: A case report.

BACKGROUND: Prostatitis caused by Brucella infection is rare and usually lacks typical lower urinary tract symptoms. However, Brucella infection can cause serum prostate-specific antigen levels to become abnormally elevated. When concurrent with lumbar vertebra infection and erosion, brucellosis can easily be misdiagnosed as prostate cancer with bone metastasis. CASE SUMMARY: A 45-year-old man complained of recurrent low back pain and fever for 2 wk. Magnetic resonance imaging of the lumbar vertebrae showed abnormal signs at the rear of the L4-5 vertebral body. Serum prostate-specific antigen level was 17.64 ng/mL, and positron emission tomography/computed tomography suggested the possibility of prostate cancer with liver and lumbar metastases. The patient was transferred to our department for further treatment. He experienced repeated bouts of fever and low back pain during hospitalization. Biopsy results indicated prostatitis. There was no significant increase in white blood cell count or procalcitonin levels. The Mycobacterium tuberculosis smear and antibody detection results were negative. Cefoperazone sulbactam was not effective. Blood culture test results were positive for brucellosis, confirming the diagnosis of brucellosis. After oral anti-infection treatment with doxycycline and rifampicin, the body temperature gradually returned to normal, and lumbago improved. After continuous treatment for 6 mo, the patient recovered. CONCLUSION: In patients with low back pain and fever accompanied by elevated prostate-specific antigen levels and lesions of the prostate and lumbar spine, a detailed medical history and blood and urine cultures should be obtained, and attention should be given to the local epidemic infectious disease situation.

A mobile terminal application program was used for endotracheal tube cuff pressure measurement.

We studied the application of a mobile terminal application program in endotracheal tube (ETT) cuff pressure measurement to improve the implementation rate of scientific ETT cuff pressure measurement and to ensure that the pressure falls within the recommended range. A pre-post controlled study lasting for 18 months was undertaken in a 40-bed general intensive care unit (GICU). This included a 6-month baseline period (baseline group) and a 6-month intervention period (intervention group). The mobile terminal application program was applied to monitor the cuff pressure of endotracheal intubation as an intervention measure during the intervention period. ETT pressure was the main outcome measure, while gender, age, causes for ICU admission, sedation score, duration of prior intubation, size of ETT, and number of VAP patients were secondary outcomes. ETT cuff pressure was monitored 742 times in both the baseline group and the intervention group. A total of 56.9% of the cuff pressure measurements in the baseline group were within the recommended range, while 78.4% of measurements in the intervention group were within the recommended range, reflecting a statistically significant difference (P < 0.05). The application of the mobile terminal application program used for ETT cuff pressure measurement could improve the percentage of ETT cuff pressure measurements falling within the recommended range.

Giant Pelvic Adenoma Originating from Ectopic Prostatic Tissue.

Ectopic prostatic tissue detected outside the genitourinary system has been rarely reported. A case with a giant pelvic adenoma that originated from ectopic prostatic tissue is presented. A 71-year male was detected with lower abdominal mass for eight months and recurrent acute urinary retention for one week. This patient already had mild lower urinary tract symptoms for three years. The physical examination, laboratory tests, ultrasonography, and MRI of this patient were analysed, and the pathological diagnosis was ectopic prostatic adenoma. The suprapubic incision for pelvic exploration and tumorectomy was chosen. The recognition and awareness of this unusual lesion is important, in order not to confuse this particular lesion with other pelvic tumors.

Rare presentation of a right retroperitoneal accessory spleen: A case report.

An accessory spleen is a congenital malformation, which is defined as ectopic splenic parenchyma. Here, an extremely rare case of a right retroperitoneal accessory spleen, mimicking a retroperitoneal neoplasm, is reported. A 40-year-old woman was referred following the incidental detection of a retroperitoneal neoplasm. Computed tomography and magnetic resonance imaging scans confirmed the presence of a retroperitoneal neoplasm at the hepatorenal recess. Retroperitoneoscopic excision was conducted, with excellent results. Pathological examination of the resected specimen revealed splenic tissue. In conjunction with a review of the literature and a discussion of the salient radiological features, the present case highlights the requirement for accurate preoperative diagnosis of an accessory spleen in the right retroperitoneal space, in order to avoid unnecessary surgical intervention.

Estrogen in combination with 5-azacitidine up-regulates p75NTR expression and induces apoptosis in 22Rv1 prostate cancer cells.

Previous studies suggest that the low-affinity neurotrophin receptor p75NTR inhibits the proliferation of human prostate cancer cells, and that estrogen interacts with p75NTR in many tissues. In this study, we exposed 22Rv1 androgen-independent prostate cancer cells to 17-ß-estradiol and the DNA demethylating agent 5-azacitidine (5-AzaC) to explore the interactions between estrogen and p75NTR. We found that estrogen induced estrogen receptor (ESR) subtype?2 and p75NTR expression in 22Rv1 cells, and that 5-AzaC further enhanced these effects. Estrogen in combination with 5-AzaC induced cell apoptosis, which was associated with the inhibition of NF-κB translocation to the nucleus. These results provide evidence that the up-regulation of ESR2 and p75NTR by estrogen plus 5-AzaC may be a potential therapeutic strategy for the treatment of androgen-refractory prostate cancer.