Case Report: Low-grade endometrial stromal sarcoma with intravenous and intracardiac extension: a case after misdiagnosis of endometrial stromal nodule as submucosal fibroid.

We present herein a rare case of large vascular and cardiac metastases of low-grade endometrial stromal sarcoma (LG-ESS) in a female patient, which occurred after misdiagnosis of endometrial stromal nodule (ESN) as submucosal leiomyoma 7 years ago. Preoperative three-dimensional CT reconstruction was used to assess the extent of the lesion. The patient underwent radical resection: thrombectomy and total hysterectomy with bilateral salpingo-oophorectomy without establishing the cardiopulmonary bypass. Intraoperative transesophageal ultrasound (TEE) was used to monitor whether the intracardiac mass was removed completely. To date, this patient is alive without any evidence of recurrence 3 years after surgery. The differential diagnosis of ESN and LG-ESS is often difficult. A clear distinction can only be reliably made after histological analysis of the tumor's entire interface with the neighboring myometrium. This case highlights that follow-ups of patients with ESN are important. Regular follow-up can detect metastasis and recurrence of misdiagnosed LG-ESS as early as possible. Distant metastasis of LG-ESS is rare, especially involving large vessels or the heart. The treatment should largely rely on multidisciplinary cooperation. Although the surgery is traumatic, the perioperative mortality rate is low, and patients can avoid death from congestive heart failure or sudden death.

Proportion of Uterine Malignant Tumors in Patients with Laparoscopic Myomectomy: A National Multicenter Study in China.

BACKGROUND: The Food and Drug Administration recently announced that the use of morcellation may cause fibroids or pelvic dissemination and metastasis of uterine sarcoma; therefore, the use of morcellation is limited in the USA. A large sample study is necessary to assess the proportion of uterine malignant tumors found in patients with laparoscopic myomectomy. METHODS: A national multicenter study was performed in China. From 2002 to 2014, 33,723 cases were retrospectively selected. We calculated the prevalence and recorded the clinical characteristics of the patients with malignancy after morcellation application. A total of 62 cases were finally pathologically confirmed as malignant postoperatively. Additionally, the medical records of the 62 patients were analyzed in details. RESULTS: The proportion of postoperative malignancy after morcellation application was 0.18% (62/33,723) for patients who underwent laparoscopic myomectomy. Nearly 62.9% (39/62) of patients had demonstrated blood flow signals in the uterine fibroids before surgery. And, 23 (37.1%) patients showed rapid growth at the final preoperative ultrasound. With respect to the pathological types, 38 (61.3%) patients had detectable endometrial stromal sarcoma, 13 (21.0%) had detectable uterine leiomyosarcoma, only 3 (3.2%) had detectable carcinosarcoma, and 5 (8.1%) patients with leiomyoma had an undetermined malignant potential. CONCLUSIONS: The proportion of malignancy is low after using morcellation in patients who undergo laparoscopic myomectomy. Patients with fast-growing uterine fibroids and abnormal ultrasonic tumor blood flow should be considered for malignant potential, and morcellation should be avoided.

Gestational Trophoblastic Neoplasia Metastasis to the Pituitary: A Case Report.

BACKGROUND: Pituitary metastasis secondary to gestational trophoblastic neoplasia (GTN) is an extremely rare condition that has not been previously reported in the literature. CASE: A 23-year-old female presented with symptoms of amenorrhea for 6 months. She was diagnosed with choriocarcinoma, and chemotherapy was scheduled. Three months after drug withdrawal she complained of headache and visualfield defects. Brain magnetic resonance images showed suprasellar and intrasellar space-occupying lesions. Pituitary metastasis of choriocarcinoma was considered. She received etoposide, methotrexate, actinomycin, etoposide, and cisplatinum multiagent chemotherapy combined with intrathecal methotrexate administration. Complete radiological remission was obtained after cessation of chemotherapy. During the 13-month follow-up period no disease progression or recurrence was noted. CONCLUSION: Pituitary metastasis of GTN is possible and is a curable disease that should be considered in young women with a history of choriocarcinoma who have neurologic symptoms. This metastasis responds well to chemotherapy.

[Reversion of resistance to cisplatin induced by MG132 in cervical cancer line HCE1 multicellular spheroid].

OBJECTIVE: To investigate the effect of the ubiquitin-proteasome pathway inhibitor MG132 on the natural resistance to cisplatin in the human cervical cancer line (HCE1) multicellular spheroid (HCE1/MCS) model and to probe it if MG132 could reverse the HCE1/MCS resistance to cisplatin, as well as the possible mechanism of drug resistance. METHODS: (1) HCE1/MCS was obtained using liquid overlay and rotating technique. (2) Four groups were established (MG132 group, cisplatin group, MG132+cisplatin group, the control group). Cell viability were measured by trypan blue exclusion assay. Cell cycle and apoptosis were detected by flow cytometry. (3) The expression of nuclear factor (NF) kappaB of both HCE1 monolayer cells (HCE1/MC) and HCE1/MCS was detected by western blot, and the expression of B cell lymphoma/leukemia-2 (bcl-2) was detected by immunohistochemistry. RESULTS: (1) HCE1/MCS was established successfully. (2) Cell inhibited rate of HCE1/MC and HCE1/MCS was: in MG132 group, (11.67+/-2.34)% vs (10.78+/-1.17)% (P>0.05); in MG132+cisplatin group, (92.67+/-2.52)% vs (91.33+/-2.18)% (P>0.05); in cisplatin group, (45.01+/-7.44)% vs (9.45+/-5.98)% (P<0.05). (3) The rate of apoptosis of HCE1/MC and HCE1/MCS were: in MG132 group, 8.14% and 5.97%; in MG132+cisplatin group, 99.01% and 95.22%; in cisplatin group, 33.61% and 0.88%. (4) The expression level of NF-kappaB and the high expression rate of bcl-2 were: in HCE1/MCS of control group, 0.67 and 60%; in HCE1/MCS of cisplatin group, 0.85 and 83%; in HCE1/MCS of MG132 group, 0.39 and 20%; in HCE1/MCS of MG132+cisplatin group, 0.47 and 33%. CONCLUSIONS: (1) HCE1/MCS present natural resistance to cisplatin and may become a good model for the study of cervical cancer drug resistance in vitro. (2) MG132 could induce the inhibition and apoptosis of HCE1/MCS cells and partially reverse the natural resistance of HCE1/MCS to cisplatin, of which partially reverse the natural resistance may be in relation to the down-regulation of NF-kappaB and bcl-2 expression.

[Inhibitory effect of quercetin on cervix cancer in mice].

OBJECTIVE: To investigate the antitumor effect and mechanism of quercetin on murine cervical carcinoma U14. METHODS: The 615-strain mice with U14 cervical cancer cells were randomly divided into 4 groups: a control, a low-dose intervention group [1.5 g/(kg . d)], a middle-dose intervention group [3.0 g/(kg . d)], and a high-dose intervention group [6.0 g/(kg . d)]. Different treatments were inoculated intraperitoneally after 6 days of transplantation and all mice were sacrificed after 26 days. The weight of tumors and inhibitory rates were measured. The expression levels of microvessel density (MVD) and nuclear factor-kappaB (NF-kappaB) were detected by immunohistochemistry. The apoptosis index (AI) was measured by terminal deoxynucleotidyl transferase assay in situ (TUNEL). RESULTS: Compared with the control group, the tumor growth in the high-dose intervention group was suppressed significantly, and the weight and volume of the tumor were markedly decreased (P<0.01). The inhibitory rate in the high-dose intervention group was higher than that in the low- and middle-dose groups(P<0.05). The expression levels of NF-kappaB and MVD were significantly decreased, and AI was enhanced in the high-dose intervention group (P<0.01). However, the low- and middle-dose quercetin had no obvious influence on the NF-kappaB expression, MVD and AI(P>0.05). CONCLUSION: Quercetin showed a marked inhibitive effect on U14 growth, and its antitumor mechanism may be associated with inhibiting the angiogenesis and inducing apoptosis.

[Inhibitory effects of human papilloma virus 18 E6 gene in HeLa cell transfected with shRNA].

OBJECTIVE: To investigate the inhibition of HPV18E6 gene in HeLa cell transfected with plasmid expressing human papilloma virus 18 E6 (HPV18E6) short hairpin RNA (shRNA). METHODS: We synthesized two HPV18E6 shRNA frames and sub-cloned them into pSUPER which can express shRNA in mammalian cells to construct pE6-1shRNA and pE6-2shRNA which were mutant in E6 shRNA frame. The pE6-1shRNA, pE6-2shRNA and pcDNA3.1 were co-transfected into HeLa cells by cationic liposome respectively and the positive transfectants were selected by G418. The HPV18E6 mRNA and protein expression level was detected by semi-quantitative RT-PCR and streptavidin-peroxidase conjugated method (SP) to assay the inhibitory effects of pE6shRNA. RESULTS: We successfully constructed several new HeLa cell lines transfected with pE6-1shRNA and pE6-2shRNA. In the HeLa cells without transfection and the HeLa cells transfected with pE6-1shRNA plasmid, the HPV18E6 mRNA levels were 1.14 +/- 0.45, 0.76 +/- 0.28 respectively, and the difference of HPV18E6 mRNA levels was significant (P < 0.05). The inhibition efficiency of HPV18E6 gene mRNA was 33.3% and the HPV18E6 protein levels were declined after transfection with pE6-1shRNA. In the HeLa cells transfected with pE6-2shRNA and pSUPER plasmids, HPV18E6 mRNA and protein expression levels were not different from those in wild HeLa cells. CONCLUSIONS: The pE6-1shRNA plasmid can inhibit HPV18E6 expression in HeLa cells, which is persistent, specific and heritable.

[Effect of progesterone on the secretion of matrix metalloproteinase-2 and matrix metalloproteinase-9 in human ectopic endometrial stromal cells].

OBJECTIVE: To determine the effect of progesterone on the secretion of matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) in ectopic endometrial stromal cells. METHODS: Ectopic endometrial stromal cells were obtained from 17 patients with endometriosis. Endometrial stromal cells were obtained from 12 patients with endometriosis and 14 cases of controls. Ectopic endometrial stromal cells of 15 cases were treated with progesterone. Culture supernatants of these stromal cells were analyzed for MMP-2 and MMP-9 by zymography. RESULTS: Endometriotic stromal cells released significantly higher levels of MMP-2 and MMP-9 than endometrial stromal cells from women with and without endometriosis. Progesterone at 10(-9) mol/L caused endometriotic stromal cells a significant reduction MMP-2 and MMP-9 levels. When progesterone concentration was increased from 10(-9) mol/L to 10(-7) mol/L, the release of MMP-9 was almost completely inhibited, wherease that of MMP-2 was not completely inhibited. CONCLUSION: Progesterone may inhibit the secretion of MMP-2 and MMP-9 in ectopic endometrial stromal cells, especially MMP-9.

[Antitumor immune response to cervix carcinoma in mice induced by HPV16 E6 DNA vaccines].

OBJECTIVE: To investigate the effect of HPV16E6 DNA vaccines on inducing the antitumor immune response to cervix carcinoma in vivo. METHODS: We prepared pCB/HPV16E6 DNA vaccines to prevent and treat 615 modle mice transplanted E6 + U14 in vivo respectively. Survival and tumor sizes of all mice were recorded and their lymphnodes and lung's metastases were detected by microscopic observation. The cytotoxicity of the spleen T cells of those mice immuned with HPV E6 DNA vaccines against the E6 U14 and U14 was detected by MTT assay. RESULTS: HPV16 E6 DNA vaccines prevented the transplanted tumor growth effectively in inbred strain mice and cured some tumor-bearing mice (P < 0. 001). Pathological results showed that the number of lymphodes with metastases foci decreased in the preventing group (P < 0.05). HPV16 E6 DNA vaccines induced special and higher cytotoxicity T lymphocytes against the E6 + U14 (P < 0.001). CONCLUSION: HPV16 E6 DNA vaccines can induce antitumor immune protection of the mice against E6 + U14 cells, suggesting that the vaccines may be effective in preventing and treating cervix cancer after an operation.

[Animal model of endometriosis treated with xenogeneic endothelial cells as vaccines in Lewis rats].

OBJECTIVE: To investigate a new therapy for endometriosis, which can inhibit the angiogenesis of ectopic endometrium. METHODS: Xeogeneic endothelial cells (human umbilical vein endothelial cells, HUVECs) were used as vaccines, and a variety of controlled cells (including rat aortic endothelial cells and human fibroblast cells) were cultured, fixed and resuspended in PBS. Thirty-six Lewis rats with experimentally induced endometriosis were divided into 6 groups. Group A was treated with HUVECs (1 x 10(5)); Group B was treated with HUVECs (5 x 10(5)); Group C was treated with HUVECs (1 x 10(6)); Group D (a control group) was treated with PBS (0.5 ml); Group E (a control group) was treated with human fibroblast cells (5 x 10(5)); and Group F (a control group) was treated with rat aortic endothelial cells (5 x 10(5)). Microvessel desity (MVD), area and the proliferative index were deteced in different groups 4 weeks after the treatment. The effect of immune serum on rat endothelial cell proliferation in vivo was determined with methyl thiazolyl tetrazolium (MTT) method. RESULTS: The area of the established endometriotic implant became smaller in Group B and Group C; compared with other groups, MVD decreased after the treatment with HUVECs as vaccines in Group B and Group C (P < 0.05). The proliferative index had no difference among these groups (P > 0.05). The immune sera induced by HUVECs could inhibit the proliferation of endothelial cells of rats in vivo (P < 0.05). CONCLUSION: As vaccines, HU- VECs can inhibit the angiogenesis of ectopic endometrium, and provide a new therapy for endometriosis.