Effect of macrophages on biological function of ovarian cancer cells in tumor microenvironment in vitro.

OBJECTIVE: To investigate the influence of two types of tumor-associated macrophages (TAMs) on the biological function of human ovarian cell lines in vitro. METHODS: (1) M2 macrophage release was induced by IL-4, and M1 macrophage release by phorbol myristate acetate (PMA) in vitro. Flow cytometry was used to distinguish these two types; (2) transwell culture system was used to establish a non-contact co-culture model of macrophage and ovarian cancer cells (SKOV3, HEY, HO8910 and A2780) in vitro. The microenvironment of ovarian cancer was simulated in vitro. (3) The proliferation, apoptosis, migration and invasion of ovarian cancer cells SKOV3, HEY, HO8910 and A2780 were analyzed after co-culture. Their proliferation was detected by CCK8 method, apoptosis by flow cytometry, Annexin V-FITC/PI double staining, invasion by Transwell assay, and migration by wound healing test. RESULTS: (1) IL-4-induced macrophages (M2) overexpressed CD163, and PMA-induced macrophages (M1) overexpressed HLA-DR. After co-culturing primary macrophages with ovarian cancer cells (SKOV3, HEY, HO8910, A2780), macrophage CD163 was highly expressed. (2) Proliferation and apoptosis of ovarian cancer cells (SKOV3, HEY, HO8910, A2780): the proliferation of ovarian cancer cells in M2 co-culture group increased compared to that in M1 co-culture group and primary co-culture group (p < 0.05); the apoptosis of ovarian cancer cells in M2 co-culture group decreased compared to that in M1 co-culture group and primary co-culture group (p < 0.05). (3) Migration and invasion of ovarian cancer cells (SKOV3, HEY, HO8910, A2780): the invasion of ovarian cancer cells in M2 co-culture group increased compared to that in M1 co-culture group and primary co-culture group (p < 0.05); the migration of ovarian cancer cells in M2 co-culture group increased compared to that in M1 co-culture group and the primary co-culture group (p < 0.05). CONCLUSION: In the simulated in vitro tumor microenvironment, co-cultured ovarian cancer cells polarized macrophages to the M2 phenotype. Furthermore, M2 macrophages enhanced the proliferation, invasion and migration, and inhibited the apoptosis of ovarian cancer cells.

Oncologic outcomes of early stage cervical cancer performed operation by different laparoscopic surgical procedures: analysis of clinical data from mutiple centers / 中华妇产科杂志

Objective:To evaluate the oncologic outcomes of different laparoscopic radical hysterectomy.Methods:From January 2011 to December 2014, the laparoscopic operation cases of cervical cancer at stage Ⅰb1, Ⅰb2, Ⅱa1 and Ⅱa2, including the histologic subtypes of squamous-cell carcinoma, adenocarcinoma and adenosquamous carcinoma, were collected in five clinical centers. The data were divided into two groups according to the surgical procedures, that is, modified laparoscopic-vaginal radical hysterectomy (mLVRH) and total laparoscopic radical hysterectomy (TLRH). The overall survival rate (OS), disease-free survival rate (DFS) at 5 years were retrospectively analyzed in this study.Results:There were 674 cases in total, including 377 cases of mLVRH, 297 cases of TLRH. (1) The OS at 5 years: the mLVRH was 96.1% and the TLRH was 92.0%, and the mLVRH was higher than that of TLRH （ P=0.010）. Stratify analysis， including stage of disease （Ⅰb1 and Ⅱa1）， histologic subtypes （squamous-cell carcinoma, adenocarcinoma）， lymph node metastasis， revealed that, ① Stage of disease: in stage Ⅰb1, the OS at five years of mLVRH was higher than that in TLRH group （98.6% vs 93.6%, P=0.012）. In stage Ⅱa1, there was significant difference between the two groups, the OS at five years of mLVRH and TLRH were 93.6% and 77.6% （ P=0.007）. ② Histologic subtypes: for the OS at five years of squamous-cell carcinoma, mLVRH and TLRH were 96.1% and 92.3%, and there was significant difference （ P=0.046）； for adenocarcinoma, the OS at five years were 91.0% and 88.6%， and there was no difference between two groups （ P=0.230）. ③ Lymph node metastasis： the mLVRH and TLRH with lymph node metastasis, the OS at five years were 98.6% and 96.4%; the mLVRH and TLRH without lymph node metastasis, the OS at five years were 89.3% and 80.8%. There were no significant differences between the two groups,respectively ( P=0.156， P=0.093）. (2) The DFS at 5 years: there was no significant difference between mLVRH and TLRH (94.1% vs 90.9%, P=0.220). Stratify analysis for stage of disease, the mLVRH group was higher than that in the TLRH group in stage Ⅰb1 (97.0% vs 92.8%, P=0.039). However, for stage Ⅱa1, there was no significant difference between mLVRH and TLRH group （88.2% vs 75.8%, P=0.074）. Conclusions:The results of this retrospective study indicated that different laparoscopy surgical procedures had diverse oncologic outcomes. The OS at 5 years of the mLVRH is superior to the TLRH. The DFS at 5 years in Ⅰb1 stage, the mLVRH is higher than the TLRH. Therefore, the modified laparoscopy is still an alternative surgery for early cervical cancer patients when following the principle of no-tumor-exposure.

Critical roles of GRP78 in carcinogenesis, growth and chemoresistance of malignancy / 国际肿瘤学杂志

GRP78,as endoplasmic reticulum resident chaperone,is highly induced by a variety of tumor microenvironmental stresses,such as hypoxia and glucose deprivation.GRP78 is implicated in tumor cell proliferation,apoptosis,invasion,metastasis and angiogenesis.Recent evidence indicates that GRP78 levels is correlated with pathological grade,stage and prognosis for the majority of solid tumors.In addition,GRP78 plays an important role in drug tolerance and knockdown of GRP78 has been shown to sensitize malignant cells.GRP78 could not only be a good biomarker to predict cancer progression and chemo-responsiveness,but also an appealing target for the development of a more selective chemotherapy.

Suppressive effect of IL-10 and TGF-β1 derived from regulatory T cells on osteoclast differentiation and bone resorption / 中华内分泌代谢杂志

ner. Furthermore, IL-10 and TGF-β1 showed a synergic effect. Conclusion IL-10 and TGF-β1, the cytokines of regulatory T cells, suppress the formation and bone resorption function of the osteoclasts.