Xiaoaiping (XAP) Injection demonstrates the anti-prostate cancer (PCa) effects, yet the underlying mechanism remains unclear. This study aims to investigate the impact of XAP on PCa and elucidate its mechanism of action. PCa cell proliferation was evaluated using a cell counting kit-8 (CCK-8) assay. Cell apoptosis was assessed through Hoechst staining and Western blotting assays. Proteomics technology was employed to identify key molecules and significant signaling pathways modulated by XAP in PCa cells. To further validate potential key genes and important pathways, a series of assays were conducted, including acridine orange (AO) staining, transmission electron microscopy, and immunofluorescence assays. The molecular mechanism of XAP against PCa in vivo was examined using a PC3 xenograft mouse model. Results demonstrated that XAP significantly inhibited cell proliferation in multiple PCa cell lines. In C4-2 and prostate cancer cell line-3 (PC3) cells, XAP induced cellular apoptosis, evidenced by reduced B-cell lymphoma 2 (Bcl-2) levels and elevated Bcl-2-associated X (Bax) levels. Proteomic, immunofluorescence, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) investigations revealed a strong correlation between forkhead box O3a (FoxO3a) autophagic degradation and the anti-PCa action of XAP. XAP hindered autophagy by reducing the expression levels of autophagy-related protein 5 (Atg5)/autophagy-related protein 12 (Atg12) and enhancing FoxO3a expression and nuclear translocation. Furthermore, XAP exhibited potent anti-PCa action in PC3 xenograft mice and triggered FoxO3a nuclear translocation in tumor tissue. These findings suggest that XAP induces PCa apoptosis via inhibition of FoxO3a autophagic degradation, potentially offering a novel perspective on XAP injection as an effective anticancer therapy for PCa.
Male ; Humans ; Prostatic Neoplasms/physiopathology* ; Autophagy/drug effects* ; Animals ; Drugs, Chinese Herbal/pharmacology* ; Proteomics ; Mice ; Apoptosis/drug effects* ; Cell Line, Tumor ; Cell Proliferation/drug effects* ; Forkhead Box Protein O3/genetics* ; Xenograft Model Antitumor Assays ; Mice, Nude ; Mice, Inbred BALB C

Objective To compare the value of diffusion kurtosis imaging (DKI) model with single-index DWI model parameters in the differential diagnosis of benign and malignant breast lesions,and to explore the correlation between the parameters and molecular subtypes and prognostic factors of breast cancer.Methods A retrospective analysis was performed with inclusion of 64 cases of breast diseases from January 2016 to May 2017 in Shanghai First People's Hospital.The patients were pathologically confirmed and typed, 30 cases are malignant tumors and 34 cases are benign lesions. DKI and DWI were performed within 2 weeks before the pathological examination. Invasive ductal carcinoma of grade Ⅰ, Ⅱ and Ⅲ were revealed in 1, 7 and 13 cases respectively. Luminal A breast cancer was found in 10 cases, Luminal B breast cancer was diagnosed in 11 cases, HER-2 positive breast cancer was 4 cases and triple negative breast cancer was 5 cases. The expressions of estrogen receptor (ER), Progesterone receptor (PR), and HER-2 positive were found in 20, 14 and 15 cases respectively. Ki67 was highly expressed in 24 cases and low expression in 6 cases. All patients underwent both plain and enhanced mammography scanning. The kurtosis (MK), mean diffusivity (MD) and ADC value were measured. Prognosis analysis was performed according to the maximum diameter (>2 cm, ≤2 cm), vascular or neurological invasion (positive, negative), lymph node metastasis (positive, negative), ER (positive, negative), PR (positive, negative), HER-2 (positive, negative),Ki67 (positive, negative), pathological grade (grade Ⅰ+Ⅱ,Ⅲ). Two independent samples t test was used to compare DKI and DWI parameters between benign and malignant lesions. ROC analysis was performed for assessing the values of parameters in discriminating benign and malignant breast lesions. Mann-Whitney U and Kruskal-Wallis H tests were used for the comparison of various prognostic factors or molecular subtypes.Spearman rank correlation analysis was used to explore the correlation of different prognostic factors and DKI and DWI parameters. Results The MK value of malignant group was higher than that of benign group,and the MD value and ADC value were lower than that of benign group (P<0.05). The area under the ROC for MK, MD and ADC were 0.897, 0.827 and 0.776, respectively. The area under the ROC was improved to 0.935 when three parameters were combined. The MK of ER positive group was higher than that of negative group (P<0.05). There was no significant difference of parameters among the other prognostic groups (all P>0.05). There was a low positive correlation between ER and MK (r= 0.417, P= 0.022). There was no correlation between the other prognostic factors and parameters (r=－0.086 to 0.313, all P>0.05). There was no significant difference in the MD, MK and ADC values among the four different subtypes of breast cancer (all P>0.05). Conclusions MK, MD and ADC values can be used to discriminate benign and malignant breast tumors, among which MK value has the best diagnostic performance. There is a certain correlation between DKI model parameters and prognostic factors.

Objective To evaluate the diagnostic efficacy of MRI diffusion kurtosis imaging (DKI) and quantitative dynamic contrast enhancement MRI (DCE-MRI) in benign and malignant breast lesions, and to explore the differential diagnosis ability for different pathological types and molecular subtype lesions. Methods Sixty four females were retrospectively enrolled in the study of MRI diffusion kurtosis imaging and quantitative dynamic contrast enhancement between November 20 and May 2017. All of them were confirmed to have benign or malignant lesions after surgical resection or puncture. All patients underwent axial T1WI, DKI and DCE-MRI examinations. The mean kurtosis (MK) and mean diffusivity (MD) values were calculated by the DKI model, and the hemodynamic parameters were obtained by quantitative dynamic contrast enhancement, including volume transfer constant (Ktrans), rate constant (Kep), extravascular extracellular space distribute volume per unit tissue volume (Ve) and blood volume fraction (Vp). Pathological analysis was performed to monitor the expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2) and nuclear proliferation index Ki67. The breast cancer was divided into Luminal A type, Luminal B type, HER-2 positive and triple-negative 4 subtypes. The differences of DKI parameters and DCE-MRI parameters between benign and malignant breast lesions were compared using two independent samples t test (normal distribution and homogeneity of variance) or Mann-Whitney U test (skewed distribution or variance). ROC analysis was used to evaluate the value of DKI and DCE-MRI parameters in differential diagnosis of benign and malignant breast lesions with pathological results as the gold standard. The Mann-Whitney U test and Kruskal-Wallis H test were used to compare the differences of DKI and DCE-MRI parameters among different prognostic factors and molecular subtypes of breast cancer. Spearman rank correlation analysis was used to evaluate the correlation between DKI and DCE-MRI parameters and different prognostic factors. Results Sixty-four cases were single lesions, with breast cancer in 23 cases and 41 cases of benign lesions. In breast cancer, there were 9 cases of Luminal A type, 7 cases of Luminal B type, 3 cases of HER-2 positive type and 4 cases of triple negative type. The positive numbers of ER, PR and HER-2 were 14, 11 and 10 cases respectively. Nineteen cases showed high expression of Ki67, while 4 cases showed low expression. There were significant differences in MK, MD, Ktrans and Kep between benign and malignant lesions (P<0.05). However, there was no significant difference between Ve and Vp (P>0.05). The area under the ROC for the differential diagnosis of benign and malignant breast lesions were 0.897, 0.808, 0.844 and 0.842, respectively. The combined multi-parameter differential diagnosis improved the efficacy. Combined with the above four parameters, the area under the ROC was 0.950. The diagnosis Sensitivity, specificity and accuracy were 0.870, 0.951 and 0.922 respectively. The Ktrans and Vp values of patients with ER positive and ER negative, as well as Ve value of deferent lymph node status, were significantly different (P<0.05), but there was no significant difference between the other prognostic factors (P>0.05). There was a moderate positive correlation between ER and Ktrans and Vp values. There was a low positive correlation between lymph node status and Ve value (r= 0.6, 0.5 and 0.4, respectively, P<0.05). No correlation was found among other parameters and prognostic factors (P>0.05). There were no significant differences in DKI and DCE-MRI parameters among different subtypes of breast cancer patients (all P>0.05). Conclusion DKI combined with DCE-MRI can improve the differential diagnosis of breast lesions and some DCE-MRI parameters are related to prognostic factors.

Objective To evaluate the feasibility of MRI-guided vacuum-assisted breast biopsy in domestic clinical prac tice.Methods A total of 45 patients with 45 suspicious breast lesions were examined with MRI-guided vacuum assisted bi opsy.The complications were observed.And the followed-up was performed.Results In 45 suspected breast lesions,43 lesions (43/45,95.56％) were successfully sampled under MRI-guided vacuum-assisted biopsy and the pathologic diagnosis was obtained.For another 2 lesions (2/45,4.44％),the pathology diagnosis were not obtained.The time to perform MRI-guided biopsy was (45.87±8.41)min for one lesion.The 5 malignant lesions (5/45,11.11％) confirmed by biopsy pathology were consistent with postoperative pathological results.For the 38 benign lesions (38/45,84.44％) confirmed by biopsy pathology,there was no malignant performance found in MRI follow-up for 6 months.Because of successful MR imaging-guided core biopsy findings,the clinic treatments were changed in 14 patients (14/45,31.11％).Five cases (5/45,11.11％) with malignant tumors were diagnosed early.The surgical biopsy was avoided in 9 benign cases (9/45,20.00 ％) who suspected as malignant.In all 45 patients,no complications occurred,such as hematoma and infection.Con clusion MRI-Guided vacuum-assisted breast biopsy is sufficient and safe for obtaining histologic proof of lesions,and plays an important role in guiding clinic treatment of some lesions visible only by MRI.