Stimulating Novel and Bioactive Metabolite Production by Cocultivation of Two Fungi─Aspergillus oryzae and Epicoccum dendrobii.

Fungi produce various bioactive secondary metabolites (SMs) as protective and weaponized tools to enhance survival in shared ecological niches. By mimicking a competitive ecosystem, cocultivation has been proven to be particularly successful in stimulating SM discovery. Here, we reported the identification of four novel metabolites, epiclactones A and B, epioxochromane and aoergostane, from the coculture of two biotechnologically important strains, Aspergillus oryzae and Epicoccum dendrobii. Transcriptome and metabolome analyses revealed widespread silent gene activation during fungal-fungal interaction. The majority of differentially expressed gene clusters were summarized for both strains. Based on these highly activated biosynthetic pathways, we suggested that a bidirectional chemical defense occurred under cocultivation. E. dendrobii enhanced the production of the spore inhibitor, fumigermin. Moreover, A. oryzae highly accumulated the antifungal agent kojic acid with a yield of up to 1.10 g/L. This study provides an excellent example for the discovery of hidden natural products by cocultivation.

Overexpression of LINC00673 Promotes the Proliferation of Cervical Cancer Cells.

OBJECTIVE: To study the expression of LINC00673 in cervical cancer and cervical intraepithelial neoplasia (CIN) and to explore the role of LINC00673 in the development of cervical cancer. METHODS: The expression of LINC00673 in serum from cervical cancer patients, CIN patients, and healthy participants was detected by RT-qPCR. The function of LINC00673 in cervical cancer cells was analyzed using in vitro and in vivo experiments. RESULTS: Our results revealed that serum LINC00673 levels were highest in cervical cancer patients, followed by patients with CIN and healthy controls. In vitro experiments demonstrated that overexpression of LINC00673 enhanced the proliferation and cell cycle progression of HeLa and SiHa cells. In vivo experiments showed that the tumor weight and volume of nude mice subcutaneously injected with LINC00673-overexpressing HeLa cells were larger than those of nude mice injected with control cells (P < 0.05). Western blotting showed that cell cycle-related proteins cyclin A2 and cyclin E and interstitial-associated proteins Snail and N-cadherin were upregulated and p53 signaling pathway-related proteins were downregulated in LINC00673-overexpressing HeLa and SiHa cells. CONCLUSION: LINC00673 plays an important role in the development of cervical cancer and may serve as a new therapeutic target for cervical cancer.

Intensity-modulated radiotherapy combined with intracavitary brachytherapy for locally advanced cervical cancer with uterus didelphys.

The purpose of this study was to investigate the clinical application of intensity-modulated radiotherapy combined with intracavitary radiotherapy for locally advanced cervical cancer complicated with uterus didelphys. We retrospectively reviewed the medical records of six patients with locally advanced cervical cancer associated with uterine malformations treated at the National Cancer Center/Cancer Hospital (Beijing, China) between 2015 and 2018. Six cases, including cervical squamous cell carcinoma (n = 3), cervical adenocarcinoma (n = 2), and clear cell adenocarcinoma (n = 1) were identified by pathological diagnosis. Uterine malformation included uterus didelphys (n = 6), with vaginal subseptum (n = 2). Six cases were treated with pelvic intensity-modulated radiotherapy. Four patients received three- dimensional intracavitary brachytherapy based on computed tomography, and two patients received conventional two-dimensional intracavitary brachytherapy. The acute and delayed responses of gastrointestinal and genitourinary toxicities were ≤grade 2 in 5 patients. Five patients achieved clinical complete remission and four patients had no recurrence during the follow-up period. One patient with cervical adenocarcinoma expired due to progression of the disease. The clinical results suggest that advanced cervical cancer associated with uterus didelphys required individual radiotherapy. The use of intensity-modulated radiotherapy combined with three-dimensional intracavitary brachytherapy is recommended in concurrent chemoradiotherapy.

IMRT and HDR-ICBT for Locally Advanced Clear Cell Adenocarcinoma of the Cervix in Uterus Didelphys Associated With Unilateral Renal Agenesis.

Clear cell adenocarcinoma of the cervix (CCAC) with genitourinary malformations is rare. Here, we report a case of CCAC in uterus didelphys (UD) associated with unilateral renal agenesis (URA) that was treated with intensity-modulated radiotherapy (IMRT) and high-dose rate intracavitary brachytherapy (HDR-ICBT). We also retrospectively reviewed the medical records of CCAC cases with genitourinary malformations treated at the National Cancer Center/Cancer Hospital (Beijing, China) between December 2006 and June 2017. Eight cases of this rare condition were identified by pathologic diagnosis. Seven patients received surgical treatment including radical hysterectomy (n = 4), modified radical hysterectomy (n = 1), and total hysterectomy (n = 2). Five patients received adjuvant radiotherapy and chemotherapy after surgery. One patient with CCAC in UD associated with URA was treated with radical IMRT and adjuvant chemotherapy. The eight patients were followed up for an average of 7.9 years; in seven cases, there was no evidence of disease recurrence, while one patient relapsed and died after 1.5 years of treatment. On the basis of these findings, locally advanced CCAC in UD associated with URA can be effectively treated with radical IMRT.

Long-Term Survival and Late Toxicity Associated With Pelvic Intensity Modulated Radiation Therapy (IMRT) for Cervical Cancer Involving CT-Based Positive Lymph Nodes.

The purpose of this study was to evaluate the outcomes and toxicity experienced by cervical cancer patients with positive lymph nodes (LNs) who were treated with intensity-modulated radiation therapy (IMRT) and intracavitary brachytherapy (ICBT) plus concurrent chemotherapy. We retrospectively evaluated 108 cervical cancer patients with computed tomography (CT)-based positive LNs treated with IMRT and ICBT plus concurrent chemotherapy between 2009 and 2011. IMRT plans were designed to deliver 50 Gy to 95% of the planning target volume (PTV; cervical tumor, pelvis, and parametrium), with daily doses of 1.6-1.8 and 60-70 Gy to 95% of the planning gross tumor volume (PGTV)-LN (pelvic or para-aortic LNs), with daily doses of 2.0-2.2 Gy. Overall survival (OS) and progression-free survival (PFS) Kaplan-Meier curves were plotted. Acute and late toxicities were evaluated according to the Radiation Therapy Oncology Group and European Organization for Research and Treatment of Cancer toxicity criteria. Of the 108 cases, 45 were stage IIB and 63 were stage IIIB. The median follow-up was 65 months (range 2-83). Overall, the 5 year cumulative incidences of pelvic failure alone, distant failure alone, and synchronous pelvic and distant failure were 8.3, 12.9, and 8.3%, respectively. The 5 year OS rate was 67.6%, and the 5 year PFS rate was 53.7%. The 5 year cumulative incidence was 9.2% for late gastrointestinal and genitourinary toxicities of Grade ≥3 and 51.8% for acute leukopenia of Grade ≥3. The clinical results suggest that IMRT and ICBT with concurrent chemotherapy is an effective treatment, with acceptable toxicity, for advanced cervical cancer involving positive LNs.

[Expression of P53, COX2 and CD44V6 in early-stage squamous carcinoma of cervix with lymph vascular space invasion positive and negative and its relationship with prognosis].

OBJECTIVE: To investigate the relationship between lymph vascular space invasion (LVSI) and various clinicopathologic factors in early-stage cervical squamous carcinoma; to explore the expression of P53, COX2 and CD44V6 in early stage squamous carcinoma of cervix and its relationship with prognosis. METHODS: A case-controlled study was conducted to compare LVSI positive group (n = 44) in early stage squamous carcinoma of cervix with LVSI negative group (n = 44). Expression of P53, COX2 and CD44V6 were evaluated by immunohistochemical method to analyze the relationship between LVSI, P53, COX2 and CD44V6 and various clinicopathologic factors and to investigate their prognostic influences. RESULTS: LVSI positive was correlated with lymph node metastasis and deep stromal invasion. The 5-year disease-free survival was 68.9% in LVSI positive group versus 94.7% in LVSI negative group (P < 0.01). And the 5-year overall survival was 70.2% in LVSI positive group versus 100% in LVSI negative group (P < 0.01) with a significant difference. COX2 was correlated with clinical stage and tumor volume while there was no correlation with P53, CD44V6 and clinical factors. The overall survival of P53, COX2 and CD44V6 positive cases were significantly shorter than that of negative ones, especially in constant positive cases of 3 markers (disease-free survival 60.0 months shorter than constant negative cases with an overall survival of 91.3 months, but there was no significant difference). CONCLUSION: LVSI is correlated with lymph node metastasis and deep stromal invasion in the early-stage squamous carcinoma of cervix while it is negatively correlated with disease-free survival and overall survival. COX2 is correlated with clinical stage and tumor volume. Furthermore P53 and CD44V6 are not correlated with clinical factors. The overall survival of P53, COX2 and CD44V6 positive cases are significantly shorter than that of negative ones.

[Impact of uterine fibroid embolization with danazol alginate microsphere on ovarian function and subsequent pregnancy].

OBJECTIVE: To investigate the impact of danazol alginate microspheres used for uterine arterial embolization (UAE) on ovarian function and subsequent pregnancy using rabbit as a model. METHODS: A total of 32 female rabbits were divided into 3 groups: a control group, danazol alginate microspheres (DKMG) group and alginate microspheres (KMG) group. Basal serum estradiol (E(2)), follicle stimulating hormone (FSH), luteinizing hormone (LH), testosterone (T) levels before UAE and 1 - 3 months after UAE were compared for all rabbits. In breeding field all rabbits mated after UAE. Estrus, and pregnancy rate were observed by veterinary. RESULTS: There were no significant changes from baseline FSH, LH, E(2), T levels measured at 1, 2 and 3 months after UAE (P > 0.05). The total pregnancy rate of DKMG or KMG group was 0 within 2 - 4 months after UAE. Compared to the control group (4/8), the difference was statistically significant (P < 0.05); the total pregnancy rate of DKMG, KMG and control groups within 5 - 7 months after UAE, respectively 17% (2/12), 25% (3/12) and 5/8 (P > 0.05); the total pregnancy rate was 42% (5/12), 50% (6/12) and 6/8 respectively within 8 - 10 months after UAE, there were also no significant differences between the three groups (P > 0.05). CONCLUSIONS: There is no obvious effect of danazol alginate microspheres used for uterine arterial embolization on ovarian function in rabbits. After UAE some animals are able to achieve pregnancies, while harmful effects are observed on short term pregnant rate.

[Clinical characters and prognosis of postpartum choriocarcinoma].

OBJECTIVE: To analyze the clinical characters and prognosis of postpartum choriocarcinoma. METHODS: Retrospective analysis of 103 patients diagnosed with postpartum choriocarcinoma in Peking Union Medical College Hospital between 1985 and 2005 was performed. RESULTS: In a total of 103 cases of postpartum choriocarcinoma treated with multiagent cytotoxic chemotherapy and combined modality therapy, 92 patients (89.3%) achieved a complete remission while 2 patients had a partial remission, and 9 patients died. Regarding 25 cases with chemorefractory choriocarcinoma and 4 relapsed cases, 18 and 3 cases achieved a complete remission respectively. According to the new International Federation of Gynecology and Obstetrics (FIGO) 2000 staging and risk factor scoring system, 17 cases were at FIGO stage I, 8 cases at stage II, 56 cases at stage III, and 22 cases at stage IV. Complete remission was achieved in 100%, 8/8, 95% and 64% respectively. Thirty-five cases in low risk group had FIGO scores < or = 6, and all achieved a complete remission. Of 68 cases in high risk group with FIGO scores > or = 7, 57 (84%) of them obtained a complete remission. There were significant differences in the two groups (P < 0.05). CONCLUSION: Postpartum choriocarcinoma could have an increasing probability of cure with early diagnosis and the use of modern multiagent cytotoxic chemotherapy and combined modality therapy.