Marine-Derived Stichloroside C2 Inhibits Epithelial-Mesenchymal Transition and Induces Apoptosis through the Mitogen-Activated Protein Kinase Signalling Pathway in Triple-Negative Breast Cancer Cells.

Background: Triterpenoid saponins from sea cucumbers exhibit significant antitumour, antifungal, and antibacterial activities. However, the associated molecular mechanisms have yet to be elucidated. In this study, we screened and explored the antitumour activity and underlying mechanisms of triterpenoid saponins isolated from Thelenota ananas. Methods: We isolated and purified sea cucumber saponins, determined their chemical structures, and confirmed their function in vitro. We also screened and explored the antitumour activity and underlying mechanisms of triterpenoid saponins isolated from Thelenota ananas. Results: Four saponins were discovered from sea cucumber Thelenota ananas collected from the South China Sea. We found that stichloroside C2 (STC2) inhibited the proliferation and clonogenesis of the human triple-negative breast cancer (TNBC) cell line MDA-MB-231 and mouse TNBC cell line 4 T1 in a dose-dependent manner and induced apoptosis and cycle arrest in these two TNBC cell lines. STC2 induced DNA damage in two TNBC cell lines and significantly increased the protein expression level of the DNA double-strand break marker γ-H2AX. STC2 downregulated the protein expression levels of phosphorylated cyclin-dependent kinase 1 (CDK1), cyclin B1, CDK2, and cyclin A2 in MDA-MB-231 and 4 T1 cells. STC2 upregulated Bax and cleaved PARP protein expression in two types of breast cancer cells. In addition, STC2 promoted E-cadherin expression; inhibited vimentin expression; upregulated the phosphorylation levels of the mitogen-activated protein kinase (MAPK) signalling pathway-related proteins p38, JNK, and ERK1/2; and downregulated Akt phosphorylation. Conclusions: STC2 exerts anti-TNBC activity, inhibits epithelial-mesenchymal transition (EMT), and induces apoptosis by regulating the cell cycle, EMT-related proteins, and MAPK signalling pathway.

Aromatic Ring Substituted Aaptamine Analogues as Potential Cytotoxic Agents against Extranodal Natural Killer/T-Cell Lymphoma.

A chemical modification study was conducted on the marine natural product aaptamine (1), isolated from the marine sponge Aaptos aaptos. Thirty new derivatives substituted by various aromatic rings at the 3- and 7-positions of aaptamine were prepared by bromination, followed by the Suzuki coupling reaction. Sixteen compounds displayed cytotoxicities to four cancer cell lines (IC50 < 10 µM). In particular, compound 5i demonstrated a significant antiproliferative effect on the extranodal natural killer/T-cell lymphoma (ENKT) cell line SNK-6 with an IC50 value of 0.6 µM. Additionally, compound 5i showed cytotoxicities to multiple lymphoma cell lines, including Ramos, Raji, WSU-DLCL2, and SU-DHL-4 cells.

Aaptolines A and B, Two New Quinoline Alkaloids from the Marine Sponge Aaptos aaptos.

Two new quinoline alkaloids, aaptolines A and B, were isolated from the marine sponge Aaptos aaptos. Their structures were determined by HR-ESI-MS data, NMR analysis, and X-ray crystallography. Structurally, aaptoline A is characterized as having a quinoline skeleton fused with a 1,4-dioxane motif at the C(7)-C(8) position, whereas aaptoline B possessed an intriguing 1H-pyrrolo[2,3-g]quinoline moiety. The cytotoxic assay of these compounds showed no cytotoxicity towards HepG2, A549, and PC9 cancer cell lines and had IC50 values greater than 20 µm.

[Facial nerve function and hearing preservation experience in middle fossa approach removal of small acoustic tumor surgery].

OBJECTIVE: The aim of this study was to investigate the hearing and facial nerve preservation in the middle fossa approach surgery for the removal of small acoustic tumor (vestibular schwannomas, VS). METHODS: A prospective database was established, and data were retrospectively reviewed. Between January 2004 and February 2013, 13 patients with acoustic tumor underwent surgery via middle fossa approach for hearing preservation. The patients consisted of six men and seven women with a mean age of 48 years. Tumor size ranged from 0.8 cm to 1.5 cm. Hearing loss was categorized as American Academy of Otolaryngology Head and Neck Surgery (AAO-HNS) class A, class B, class C and class D. Facial nerve function was evaluated according to House-Brackmann (HB) Grade I-VI. RESULTS: Gross-total resection was accomplished in 12 of 13 patients. Preoperative hearing as class A in ten, class B in two, and class C in one patient respectively. Postoperatively, hearing was graded as class A in eight patients, class B in 3, and class C in 2 patients. Facial nerve function was House-Brackmann (HB) grade I in twelve patients, grade II in one patient preoperatively. Postoperatively, facial nerve function was HB Grade I in twelve patients and Grade III in one patient. The overall hearing preservation rate was at least 80% (8/10) and HB Grade I facial nerve outcome of 100% (12/12) . All cases were followed up for 0.5 to 5 years, no complications were observed. CONCLUSIONS: The middle fossa approach for the resection of small VS with hearing preservation is a viable and relatively option. It should be considered among the various options available for the management of small and growing VS.

[Expression of S518 phosphorylated Merlin and its interaction with CD44 in vestibular schwannoma].

OBJECTIVE: To investigate the impact of S518 phosphorylation in Merlin on the interaction with CD44 in vestibular schwannoma and the tumor growth. METHODS: Thirty-five samples of vestibular schwannoma were identified by pathology. Immunohistopathology and western blot were employed to analyze the expression and localization of S518 phosphorylated Merlin in the tumor tissues. Nerve tissues that were collected during other surgical operation were used as control. The expression level of S518 phosphorylated Merlin was compared with clinical stages, tumor size, clinical course and cystic degeneration. Immunoprecipitation was used to evaluate the impact of S518 phosphorylation in Merlin on the interaction with CD44. RESULTS: In vestibular schwannoma, Merlin was phosphorylated at S518 and demonstrated perinuclear localization. The S518 phosphorylation level was much lower in the normal control nerve tissues than that in vestibular schwannoma tissues. There was no correlation between the phosphorylation level on Merlin and clinical stages, tumor size, clinical course and cystic degeneration. The S518 phosphorylated Merlin bound CD44 was higher than wild-type Merlin bound CD44 in vestibular schwannoma tissues. CONCLUSIONS: The affinity of Merlin to CD44 was increased after phosphorylation at S518. Different cellular biological results might be triggered through binding to wild type Merlin and S518 phosphorylated Merlin.

[Expression and localization of merlin in vestibular schwannoma].

OBJECTIVE: To clarify the expression and subcellular localization of merlin in vestibular schwannoma. METHODS: Fifty four paraffin embedded vestibular schwannoma samples confirmed by pathology after resection were included in the study. The expression of merlin in vestibular schwannoma was analyzed by immunohistochemistry. Nerve tissues that were resected during surgical treatment for trigeminal neuralgia and Meniere's disease were used as control. Western blotting was used to analyze the electrophoresis migration of merlin in the acoustic neuroma. Image analysis was used to calculate the positive expression percentage of merlin in each individual. The expression percentage of merlin in the tumor tissue was compared with age and gender of the patients, clinical course of the tumor, tumor growth index, tumor diameter and clinical stage. RESULTS: Merlin was expressed in 0 to 87.5% of the cells in vestibular schwannoma tissue with a mean of (46.66 +/- 5.75)%. There was a negative correlation between merlin expression percentage and tumor growth index. There were no correlations between merlin expression percentage and the age, gender, tumor diameter and clinical stage. There exists a difference for the location of merlin, mainly in the nucleus and perinucleus. There was also a cytoplasmic location. Merlin in the tumor tissue was shown by western blot to be in 65000 and 125000 positions. CONCLUSIONS: Merlin was expressed in vestibular schwannoma tissue, with a different intra-cellular location. Merlin might also exist as a complex with other proteins in the tumor tissue.

[Laparoscopic radical hysterectomy and pelvic lymphadenectomy: analysis of 14 cases].

OBJECTIVE: To evaluate the feasibility and safety of surgical removal of the tumors through laparoscopy in patients with early-stage uterine cancer. METHODS: A retrospective analysis of the clinical data of 10 cervical cancer and 4 endometrial cancer cases, in which laparoscopic radical hysterectomy and pelvic lymphadenectomy were performed following the same surgical procedures as in laparotomy. RESULTS: The mean operating time was 302 min, and mean estimated blood loss was 760 ml, with the mean postoperative gastrointestinal recovery time of 30 h and average number of removed lymph nodes of 22. CONCLUSION: Laparoscopic surgery has equivalent curative effect to laparotomy, and laparoscopic radical hysterectomy and pelvic lymphadenectomy in the patients with early-stage uterine cancer is both feasible and efficient.