Glycine Decarboxylase (GLDC) Plays a Crucial Role in Regulating Energy Metabolism, Invasion, Metastasis and Immune Escape for Prostate Cancer.

Glycine decarboxylase (GLDC) is one of the core enzymes for glycine metabolism, and its biological roles in prostate cancer (PCa) are unclear. First, we found that GLDC plays a central role in glycolysis in 540 TCGA PCa patients. Subsequently, a metabolomic microarray showed that GLDC enhanced aerobic glycolysis in PCa cells, and GLDC and its enzyme activity enhanced glucose uptake, lactate production and lactate dehydrogenase (LDH) activity in PCa cells. Next, we found that GLDC was highly expressed in PCa, was directly regulated by hypoxia-inducible factor (HIF1-α) and regulated downstream LDHA expression. In addition, GLDC and its enzyme activity showed a strong ability to promote the migration and invasion of PCa both in vivo and in vitro. Furthermore, we found that the GLDC-high group had a higher TP53 mutation frequency, lower CD8+ T-cell infiltration, higher immune checkpoint expression, and higher immune exclusion scores than the GLDC-low group. Finally, the GLDC-based prognostic risk model by applying LASSO Cox regression also showed good predictive power for the clinical characteristics and survival in PCa patients. This evidence indicates that GLDC plays crucial roles in glycolytic metabolism, invasion and metastasis, and immune escape in PCa, and it is a potential therapeutic target for prostate cancer.

Optimal Starting Age and Baseline Level for Repeat Tests: Economic Concerns of PSA Screening for Chinese Men - 10-Year Experience of a Single Center.

OBJECTIVE: To investigate the optimal age for the baseline serum prostate-specific antigen (PSA) test and for repeat screening and its economic burden in a single center in China. MATERIALS AND METHODS: 35,533 men with PSA screening were retrospectively enrolled in this study. Follow-ups were conducted in 1,586 men with PSA >4 ng/mL, and receiver-operating characteristic (ROC) curves were employed to investigate the optimal cutoffs. RESULTS: ROC analysis indicated that the optimal age for initial PSA screening was 57.5 years (AUC = 0.84), 62.5 years (AUC = 0.902), 60.5 years (AUC = 0.909), and 61.5 years (AUC = 0.890) for individuals with PSA >4 and >10 ng/mL, a diagnosis of prostate cancer (PCa), and clinically significant PCa defined as the focus events, respectively. For Chinese men aged 50-59, 60-69, and >70 years, the initial PSA levels of 1.305 ng/mL (AUC = 0.699), 1.975 ng/mL (AUC = 0.711), and 2.740 ng/mL (AUC = 0.720) might have a PSA velocity >0.75 ng/mL per year during the follow-up. In addition, the total cost amounts to CNY 13,609,260 in these cases, but only 60 of the 35,533 (0.17%) men gained benefit from PSA screening. CONCLUSION: In our opinion, the optimal starting age for initial PSA testing was 57.5 years. The necessity for repeat screening should be based on the first PSA level depending on age. A cost--benefit analysis should be included in population-based screening.

[Study on Autophagy and Apoptosis Induced by Amiodarone Combined with Glycyrrhetinic Acid in HepG2 Cells].

OBJECTIVE: To investigate the effects of amiodarone combined with glycyrrhetinic acid on the activity, apoptosis and autophagy in human hepatoma HepG2 cells. METHODS: After using amiodarone and glycyrrhetinic acid alone or in combination treatment for HepG2 cells, MTT assay was used to detect cell proliferation, Annexin Ⅴ/PI flow cytometry was used to detect apoptosis; Western blot was used to detect the expression of autophagy-related proteins Beclin-1, LC3 and p62. The formation of EGFP-LC3 green fluorescent aggregates was observed under a fluorescence microscope. The effects of autophagy on cell proliferation and apoptosis were studied by autophagy inhibitor hydroxychloroquine (HCQ) and autophagy promoter Rapamycin. RESULTS: The cell viability in combination group was lower than that in single drug group, and the apoptosis rate was higher than that in single drug group. Compared with single-drug group, the expressions of Beclin-1 and LC3Ⅱ protein in the combination group were higher than that in the single-drug group, while the expression of p62 protein was lower in the single-drug group. Fluorescence microscopy results showed that the number of EGFP-LC3 fluorescent aggregates in the combination group were more than that in the single-drug. Using amiodarone and glycyrrhetinic acid treated HepG2 cells, inhibition of auotophagy could decrease cell viability, increase apoptosis rate of cells; promoting autophagy would decrease the apoptosis rate and increase cells viability. CONCLUSION: By increasing apoptosis of hepatocellular carcinoma HepG2 cells and autophagy level, and decreasing the cell activity, amiodarone combining with glycyrrhetinic acid treatment inducing autophagy a protective mechanism for cells.

[Application value of real-time contrast-enhanced ultrasound in transrectal prostate biopsy].

OBJECTIVE: To explore the application value of real-time contrast-enhanced ultrasound (RTCEU) in improving the detection rate of transrectal ultrasound-guided prostate biopsy. METHODS: This prospective study included 91 male patients with abnormally high PSA (4－20 µg/L) or abnormalities in DRE or MRI, who underwent 12+X prostate biopsy following conventional transrectal ultrasonography (TRUS) and RTCEU examination. We compared the numbers of suspected prostatic nodules before and after RTCEU as well as the detection rates of prostate cancer between conventional TRUS-guided 12PBx and 12PBx plus lesion-targeted biopsy procedures. RESULTS: Totally, 57 of the 86 suspected lesions on TRUS (66.3%), and 108 of the 118 abnormal nodules on RTCEU (91.5%) were confirmed to be prostate cancer. RTCEU achieved a significantly higher detection rate than TRUS (P<0.01). A total of 39 cases of prostate cancer (42.8%) were detected by RTCEU, while only 28 (30.7%) by TRUS, with statistically significant difference in the detection rate between the two procedures (P=0.033). CONCLUSIONS: Real-time contrast-enhanced ultrasound can significantly improve the detection rate of prostate cancer and provide a valuable guide to targeted prostate biopsy.

Treatment of a non-typical hepatic pseudolesion complicated by greatly elevated alpha fetoprotein: case report and literature review.

BACKGROUND: Hepatic pseudolesions detected by helical computed tomography (CT) are not rare, but it is difficult to make a final diagnosis when the hepatic lesion is complicated by the presence of greatly elevated alpha fetoprotein (AFP). Clinical treatment of non-typical hepatic pseudolesions complicated by greatly elevated AFP should confirm the diagnosis and minimize trauma. CASE PRESENTATION: Non-invasive procedures including ultrasonography, CT, and micro-invasive digital subtraction angiography could not safely differentiate this lesion from a malignant focus when it was complicated by greatly elevated AFP. Laparoscopic hepatectomy was performed, and pathological analysis showed chronic hepatitis, nodular regenerative hyperplasia, focal nodular hyperplasia of the liver, and mild vascular malformation. The tissue was HbsAg(-), HbcAg(-), and AFP(+). CONCLUSION: Heightened awareness of hepatic pseudolesion complicated by primarily elevated AFP will help physicians avoid unnecessary invasive procedures. Hepatic biopsy is inevitable because of greatly elevated AFP. For suspected hepatic pseudolesion with elevated AFP, needle-core biopsy and follow-up surveillance instead of hepatectomy are recommended to find the source of AFP and make a final diagnosis of pseudolesion.

Metaplastic carcinoma of the right breast and simultaneous giant ovarian teratoma: a case report.

We describe here a female patient who presented with a breast mass and giant abdominal mass. Fine needle aspiration cytology of the breast mass and histological examination after modified radical mastectomy confirmed metaplastic carcinoma of the breast. The epithelial components were formed by infiltrating ductal carcinoma with poor differentiation, and the sarcomatous components were formed by fibrosarcoma and osteosarcoma. Histological examination of the abdominal mass confirmed ovarian teratoma. The patient underwent modified radical mastectomy of the right breast and laparoscopic excision of the abdominal mass in the lower right quadrant. Having underwent six courses of chemotherapy, the patient is now in her tenth month after surgery and under follow-up, and she has no relapsed disease. These two diseases have never seen in one patient before. The case we report here provides some new data for research and clinical experience and it may also provide a new insight into the relationship between metaplastic breast carcinoma and ovarian teratoma.

[Co-expression of CD99/MIC2 and ALK in anaplastic large-cell lymphoma tissues and its significance].

OBJECTIVE: To investigate co-expression of CD99/MIC2 and anaplastic lymphoma kinase (ALK) protein in anaplastic large-cell lymphoma (ALCL) tissues and Karpas 299 cells and its significance. METHODS: Clinical prognoses and ALK protein expressions of 25 cases of ALCL were reviewed retrospectively, the median duration of survival was analyzed for patients with ALK(+) ALCL and ALK(-) ALCL. Histological and immunohistochemical staining were applied to other 25 cases of ALCL and paraffin-embedded tissue from human anaplastic large-cell lymphoma Karpas 299 cells to detect the protein of CD99 and ALK. RESULTS: Of former 25 cases of ALCL, median duration of survival for ALK(+) patients was 59 months, whereas 20 months for ALK(-) patients. The prognosis of ALK(+) group was better than that of ALK(-) group, survival curves of these two groups showed statistically significant (P < 0.05). CD99 was positive in 18 cases (72.0%) while negative in 7 cases (28.0%) of the latter 25 ALCL, ALK was positive in 19 cases (76.0%) while negative in 6 cases (24.0%); Of 19 ALK(+) ALCL, 16 (84.2%) cases co-expressed CD99-ALK; and in 6 ALK(-) ALCL, 2(33.3%) were CD99-ALK double negative, the expression of CD99 protein strongly correlated with that of ALK protein (P < 0.05). ALK and CD99 protein expressed in Karpas 299 cells with diffuse distribution. CONCLUSIONS: CD99 highly expressed in ALCL, and showed high rate of co-expression with ALK. CD99 protein expression could be considered as a helpful diagnostic and prognostic factor of ALCL, especially for ALK(+) ALCL.

Malignant paraganglioma originating from the kidney: a case report and literature review.

Paraganglioma is a rare neuroendocrine tumor arising from the undifferentiated cells of the primitive neural crest. We report a case of malignant paraganglioma originating from the left kidney. The 55-year-old female patient was admitted for intractable cough for a month and the presence of a solid mass in the left lung detected by computer tomography (CT). Sonography revealed a mass in the left kidney after admission. Complete surgical resection of the tumor was performed and the diagnosis of malignant paraganglioma originating from the left kidney was established pathologically. During the follow-up for 12 months, the patient showed a good general condition and sonography revealed no evidence of recurrence. Based on these findings, we discussed the diagnosis of this disease using medical imaging modalities.

[Expression of hypoxia-inducible factor-1alpha and matrix metalloproteinase-2 in degenerative lumbar intervertebral disc].

OBJECTIVE: To investigate the expression of hypoxia-inducible factor-1alpha (HIF-1alpha) and matrix metalloproteinase-2 (MMP-2) in degenerative human intervertebral disc. METHODS: Specimens of the nucleus pulposus of the degenerative discs were obtained from patients with lumbar disc herniation (experimental group), and those from young patients suffering thoracolumbal vertebral bursting fracture served as the control. The experimental group was divided into three subgroups according to the magnetic resonance imaging (MRI) results. The tissue specimens from all the groups were examined for HIF-1alpha and MMP-2 expressions using immunohistochemistry. RESULTS: The tissues in the experimental group showed significantly higher expressions of HIF-1alpha and MMP-2 than those in the control group (P<0.05), and the expressions increased significantly with the severity of the degenerative changes of the intervertebral discs (P<0.05). A positive correlation was found between the expressions of the HIF-1alpha and MMP-2 in degenerative intervertebral discs. CONCLUSION: HIF-1alpha and MMP-2 may participate in the degeneration of human intervertebral discs, in which process their expressions show a common pattern of enhancement with the progression of the condition.