Spore Oil enhances the effect of cyclophosphamide inhibiting programmed death-1 and prolongs the survival of H22 tumor-bearing mice.

OBJECTIVE: To investigate the effect of Ganoderma Lucidum Spore Oil (GLSO) on the tumor growth and survival of H22 tumor-bearing mice treated with cyclophosphamide (CTX), and explore the underlying mechanism. METHODS: Allograft H22 hepatocellular carcinoma mouse model was applied to investigate the effect of GLSO on the tumor growth and survival of animals, and Kaplan-Meier survival analysis was used to analyze the life span. Plasma biochemical examination was used to determine the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea (UREA) and creatinine (CRE). Western blot analysis was performed to detect Programmed Death-1 (PD-1), Programmed Death Ligand 1 (PD-L1), Janus Kinase 2 (JAK2), phosphorylated Signal Transducer and Activator of Transcription 3 (p-STAT3), and Signal Transducer and Activator of Transcription 3 (STAT3) expression. RESULTS: GLSO increased the anti-tumor effect of CTX and prolonged the survival of H22 tumor-bearing mice treated with CTX. Meanwhile, GLSO increased the thymus index and showed no obvious toxicity to liver functions of animals. GLSO also decreased the level of UREA in H22 tumor-bearing mice treated with CTX. Furthermore, GLSO could inhibit the expression of PD-1 in spleen, which was independent of JAK2 expression and STAT3 phosphorylation. However, GLSO did not affect the expression of PD-L1, JAK2, and p-STAT3 in tumor tissue. CONCLUSION: GLSO could strengthen the anti-tumor effect of CTX and prolong the life span of H22 tumor-bearing mice, while the underlying mechanism might be relevant to the amelioration effect of thymus function and inhibition of PD-1 expression in spleen. Furthermore, these findings implied the promising role of GLSO in combination with CTX to extend the survival of patients in clinical chemotherapy of hepatocellular carcinoma.

[Pregnancy-preserving and maternal-fetal management in a patient with rare large cell neuroendocrine carcinoma of the uterine cervix].

OBJECTIVE: To explore the strategy of pregnancy-preserving and maternal- fetal management in patients with primary gynecologic neuroendocrine tumors (gNETs) during pregnancy. METHODS: We performed whole genome sequencing (WGS) for analyzing maternal and fetal somatic and germline single nucleotide variations (SNVs) and small insertions and deletions (InDels) for a 29-year-old pregnant woman diagnosed with stage IB2 large cell neuroendocrine carcinoma (LCNEC) and adenocarcinoma in the cervix. A systematic literature review was performed to explore the strategies for treatment of such rare histological type while maintaining pregnancy. RESULTS: Global case analysis of cervical NETs during pregnancy suggested that negative lymph node metastasis and an early FIGO stage were potentially associated with a good prognosis of the patients. In the case presented herein, a pregnancy-preserving strategy was adopted and favorable maternal-fetal outcomes were achieved after neoadjuvant chemotherapy, radical surgery and postoperative systemic chemotherapy. At 35+5 weeks, the fetus was delivered by caesarian section, and the patient has by now had a disease-free survival of 19 months postoperatively. WGS analysis revealed 6 missense somatic pathogenic mutations in two cancer tissues of the patient, and among them KARS and VEGFA were related with targeted therapy. Five pathogenic germline variants were detected in the patient and her son, suggesting the necessity of a long-term follow-up schedule including precise genetic counselling for both the mother and the child. CONCLUSIONS: Although gNETs in pregnancy are rare and highly risky, pregnancy-preserving managements of gNETs can still be considered and favorable maternalfetal outcomes are possible with proper assessment of the clinical indications and implementation of multimodal treatments. Precise treatment and follow-up strategies based on the results of WGS for risk-reducing intervention of cancer recurrence or occurrence can potentially benefit the patient and the neonate.

Survivin is not a promising serological maker for the diagnosis of hepatocellular carcinoma.

Survivin expression in the serum of patients with hepatocellular carcinoma (HCC) and nonmalignant chronic liver diseases remain to be elucidated. The aims of the present study were to evaluate the diagnostic role of survivin in the serum of patients with HCC and identify which ELISA kit performed best in detecting the levels of serum survivin. In total, 80 patients were included in the present study, including 20 patients with HCC, 20 patients with liver cirrhosis, 20 patients with chronic hepatitis B virus infection and 20 healthy volunteers. The levels of survivin protein in the serum were detected using two different ELISA kits (R&D and Abnova). The positive ratios of serum survivin detected by the R&D ELISA kit in all the cases were 8.75% (7/80; median, 0 pg/ml; range, 0-39.8 pg/ml) and in HCC patients were 5% (1/20; median, 0 pg/ml; range, 0-39.8 pg/ml). For the same samples analyzed using the Abnova ELISA kit, the positive ratios of serum survivin in all the cases were 22.5% (18/80; median, 0 pg/ml; range, 0-553.5 pg/ml) and in HCC patients were 25% (5/20; median, 0 pg/ml; range, 0-93.5 pg/ml). The results obtained by the different ELISA kits demonstrated no statistically significant differences in the level of survivin between HCC patients and healthy controls. The correlation coefficient was 0.0064 (P=0.481) when analyzing the same serum samples with the different ELISA kits. In addition, the highest positive ratio of serum survivin was observed using the Abnova kit. A statistically significant difference in the results was observed between the R&D and Abnova kits. In general, the levels and positive ratios of serum survivin in the patients with HCC were significantly low. Furthermore, no difference was observed between HCC patients and controls in regard to the levels of serum survivin detected by the R&D and Abnova ELISA kits. In conclusion, survivin is unlikely to be a promising serological maker for the diagnosis of HCC.

BMI-1, a promising therapeutic target for human cancer.

BMI-1 oncogene is a member of the polycomb-group gene family and a transcriptional repressor. Overexpression of BMI-1 has been identified in various human cancer tissues and is known to be involved in cancer cell proliferation, cell invasion, distant metastasis, chemosensitivity and patient survival. Accumulating evidence has revealed that BMI-1 is also involved in the regulation of self-renewal, differentiation and tumor initiation of cancer stem cells (CSCs). However, the molecular mechanisms underlying these biological processes remain unclear. The present review summarized the function of BMI-1 in different human cancer types and CSCs, and discussed the signaling pathways in which BMI-1 is potentially involved. In conclusion, BMI-1 may represent a promising target for the prevention and therapy of various cancer types.