Curcumin induces apoptotic cell death and protective autophagy by inhibiting AKT/mTOR/p70S6K pathway in human ovarian cancer cells.

PURPOSE: Curcumin (Cur), a yellow-colored dietary flavor from the plant (Curcuma longa), has been demonstrated to potentially resist diverse diseases, including ovarian cancer, but drug resistance becomes a major limitation of its success clinically. The key molecule or mechanism associated with curcumin resistance in ovarian cancer still remains unclear. The aim of our study was to investigate the effects of curcumin on autophagy in ovarian cancer cells and elucidate the underlying mechanism. METHODS: In our study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), EdU proliferation assay and colony-forming assay were used to assess cell viability. Apoptosis was detected by western blot and flow cytometric analysis of apoptosis. Autophagy was defined by both electron microscopy and immunofluorescence staining markers such as microtubule-associated protein 1 light chain 3 (LC3). Plasmid construction and shRNA transfection helped us to confirm the function of curcumin. RESULTS: Curcumin reduced cell viability and induced apoptotic cell death by MTT assay in human ovarian cancer cell lines SK-OV-3 and A2780 significantly. Electron microscopy, western blot and immunofluorescence staining proved that curcumin could induce protective autophagy. Moreover, treatment with autophagy-specific inhibitors or stable knockdown of LC3B by shRNA could markedly enhance curcumin-induced apoptosis. Finally, the cells transiently transfected with AKT1 overexpression plasmid demonstrated that autophagy had a direct relationship with the AKT/mTOR/p70S6K pathway. CONCLUSIONS: Curcumin can induce protective autophagy of human ovarian cancer cells by inhibiting the AKT/mTOR/p70S6K pathway, indicating the synergistic effects of curcumin and autophagy inhibition as a possible strategy to overcome the limits of current therapies in the eradication of epithelial ovarian cancer.

The association of depressive symptoms and medication adherence in asthma patients: The mediation effect of medication beliefs.

BACKGROUND: The significant role of depression in influencing medication beliefs, which are pivotal cognitive factors that strongly influence medication adherence, has been established. Poor adherence to asthma-controlled medication poses an significant barrier to achieving optimal asthma management. OBJECTIVE: To explore the potential mediating effects of medication beliefs on the relationship between depressive symptoms and medication adherence in patients with asthma. METHODS: Demographic and clinical characteristics, depressive symptoms, medication adherence, and medication beliefs were collected using questionnaires. Structural equation modeling, was utilized to model medication beliefs as mediators in the relationship between depressive symptoms and medication adherence. Bootstrapping was performed to analyze the mediation- and contrast-specific indirect effects of the two medication beliefs. RESULTS: Among the patients who participated in the study, 29.6 % with depressive symptoms were more prone to poor adherence and exhibited skepticism toward asthma medications. Depression had a direct effect (direct effect = -0.275, 95%CI: -0.369 to -0.190) and an indirect effect on adherence mediated by medication beliefs (indirect effect = -0.168, 95%CI: -0.224 to -0.121). The specific mediation effect of concern belief was stronger than that of necessity belief (difference = -0.076, 95%CI: -0.132 to -0.029). CONCLUSION: Depressive symptoms have a direct impact on medication adherence as well as an indirect effect mediated by beliefs about medication, particularly concerns belief.

Impact of perioperative red blood cell transfusion on the prognosis of patients with epithelial ovarian cancer.

Background: Surgery for advanced ovarian cancer tends to be extensive. We performed an analysis to determine whether perioperative red blood cell transfusion (PRBCT) is associated with a poor prognosis in women with epithelial ovarian cancer (EOC). Methods: Our retrospective analysis included 314 women. The Mann-Whitney rank-sum test and chi-square test were used to analyze the clinical characteristics of the PRBCT and non-PRBCT groups, and Cox proportional hazard models were used for the multivariate analysis. Results: PRBCT was associated with higher relapse and mortality rates in 121 (38.54 %) patients. After multivariate analysis, transfused patients were 1.59 times at risk of death (hazard ratio [HR] = 1.59; 95%CI, 1.12-2.25) and 1.63 times at risk of recurrence (HR = 1.63; 95%CI, 1.22-2.18) than non-transfused patients. Conclusions: PRBCT could prolong hospital stay, and increased hospital costs were significantly associated with increased cancer recurrence and overall mortality in patients with EOC.

Enhanced Recovery After Surgery Impact on the Systemic Inflammatory Response of Patients Following Gynecological Oncology Surgery: A Prospective Randomized Study.

OBJECTIVE: Enhanced recovery after surgery (ERAS) protocol has widely gained acceptance in gynecological surgery. Its safety and efficacy should be evaluated fully via well-designed, randomized, control trials. The main objective of our study is to compare the ERAS protocol with the conventional perioperative care program after gynecological oncology. Furthermore, the secondary objectives of our study are the identification of markers that allow us to evaluate the effectiveness of the application of ERAS elements in the modulation of the body's response to surgical stress. METHODS: Patients with gynecological tumors indicated for surgery were randomly assigned to either the ERAS group or the conventional group. The ERAS protocol included short fasting time, fluid restriction, early oral feeding, reduced opioid consumption and immediate mobilization after surgery. The primary endpoint was the reduction of hospital stay in the ERAS group. The day of first flatus, postoperative nausea and vomiting (PONV), maximum pain score by the visual analogue scale (VAS) and complication, readmission rate, reoperation rate, postoperative mortality, total hospital cost and systemic inflammatory response (SIR) were secondary endpoints. RESULTS: A total of 130 patients in gynecological tumor surgery were enrolled (ERAS = 65, conventional = 65). The ERAS group had faster bowel function recovery, significantly less pain, less PONV, shorter hospital stay, and less total hospital costs. SIR markers were estimated and screened out that postoperative platelet, neutrophil-lymphocyte-ratio (NLR) and platelet-lymphocyte-ratio (PLR) were significantly lower in ERAS groups compared to conventional groups. CONCLUSION: The implementation of ERAS protocol is safe and enhances postoperative recovery after gynecological oncology surgery. We firstly reveal the beneficial effect of ERAS protocols on the alleviation of postoperative SIR, which is a reflection of the magnitude of surgical trauma. Postoperative platelet, NLR or PLR could be the novel and inexpensive markers to assess how ERAS protocols modulate gynecological oncology surgery. TRIAL REGISTRATION: The trial was registered in ClinicalTrials.gov (NCT03629626).

Fertility-sparing management of low-grade endometrial stromal sarcoma: analysis of an institutional series, a population-based analysis and review of the literature.

BACKGROUND: Low-grade endometrial stromal sarcoma (LGESS) is the second most common malignant mesenchymal tumor of the uterus which usually affects young women. However, the researches on the safety and feasibility of the fertility-sparing management of it are limited. METHODS: A retrospective analysis was performed including 5 women diagnosed with LGESS treated with fertility-sparing management at Qilu Hospital of Shandong University from 2010 to 2019. Besides that, 1,070 patients diagnosed with LGESS in SEER database from 1973 to 2016 were examined. By using the Kaplan-Meier method, survival curves were estimated, and comparisons of statistical significance were performed with the stratified log-rank test within each group. RESULTS: Five patients with LGESS were enrolled in this study. All patients were submitted to fertility-sparing surgeries, after surgery, they all continued hormonal therapy for one year. Four out of the 5 patients recurred, to be more exact, 3 of them recurred in uterus and the other one in the uterus and iliac vascular region. They all suffered further surgery and all 5 patients were alive at the time of last contact. Besides, among these patients, two conceived naturally and delivered a healthy baby by cesarean section. Among 1,070 patients in SEER database, only 28 (2.6%) patients underwent local tumor excision, including excisional biopsy (39%), myomectomy (25%), laser ablation or excision (4%) and polypectomy (4%). There was no statistical significance was observed among TH±BSO, radical hysterectomy, subtotal hysterectomy and local tumor excision (P=0.29). CONCLUSIONS: Our analysis indicated that for those young LGESS patients who wish to preserve their fertility, the feasibility and safety of fertility-sparing management should be considered after gynecological oncologist and gynecological pathologist making professional decisions.

Pathological features, clinical presentations and prognostic factors of ovarian large cell neuroendocrine carcinoma: a case report and review of published literature.

BACKGROUND: There is no consensus on the optimal chemotherapy regimen and the prognostic factors for ovarian large cell neuroendocrine carcinoma (LCNEC), a rare type of tumor. The objective of the present study is to present the case of a recent encounter of pure ovarian LCNEC and perform a brief review to summarize the clinicopathological features and prognostic factors of 57 cases of LCNEC patients that have been previously reported. METHOD: CASE PRESENTATION: Eligible studies were searched for online and 57 cases with clear follow-up data were found to have been reported. We present the 58th case, which is of a 70-year-old woman with stage IIIc primary pure LCNEC of the ovary. The initial symptom of this patient was abdominal distension (more than 2 months). A recent ultrasound test showed a solid-cystic mass occupying the pelvic and abdominal cavity. She received two courses of cisplatin-etoposide chemotherapy as an adjuvant therapy. No signs of nonclinical or radiological evidence of disease recurrence was found at follow-up examinations during the first 3 months after operation. A retrospective review of these 58 cases was conducted and survival curves were estimated. Using the Kaplan-Meier method. CONCLUSION: The patients included were aged between 18 and 80 years. A Kaplan-Meier survival curve revealed that the median overall survival was 10.000 months, while 26 (44.83%) patients died within 12 months. We compared the overall mean survival time of all patients with that of stage I patients (42.418 vs 42.047 months), which suggests that ovarian LCNEC has a very poor prognosis even at stage I. Mean survival was longer for patients who had undergone postoperative chemotherapy than for those without postoperative chemotherapy (48.082 vs 9.778 months). A small series, such as this, does not provide adequate data to establish a firm correlation between the postoperative chemotherapy and prognosis (p = 0.176). In our review of 58 cases with ovarian LCNEC, prognosis was unfavorable in most cases. Given the rarity of LCNEC, it is highly recommended that a global medical database of ovarian LCNEC and a standard system of diagnosis and treatment is established.

Cellular leiomyoma with necrosis and mucinous degeneration presenting as pseudo-Meigs' syndrome with elevated CA125.

Pseudo-Meigs' syndrome is a syndrome rarely caused by leiomyomas. Elevated CA125 usually suggests malignancy of the ovary. No reported case of pseudo-Meigs' syndrome presenting with necrosis and mucinous degeneration of uterine cellular leiomyomas (CLs) and an elevated CA125 level was found upon a PubMed search. A 37-year-old woman presenting with massive ascites, bilateral pleural effusions and a pelvic mass measuring 20 x 18 x 10 cm is described. The pre-operative serum CA125 was 920.4 U/ml. After total abdominal hysterectomy and partial omentumectomy, the final pathologic diagnosis was CL with focal hemorrhage, necrosis and mucinous degeneration. The ascites and pleural effusion disappeared, and the CA125 level returned to normal in one month. Benign leiomyoma accompanied by pseudo-Meigs' syndrome and elevated serum CA125 can mimic a pelvic malignancy.

Coexistence of benign struma ovarii, pseudo-Meigs' syndrome and elevated serum CA 125: Case report and review of the literature.

Struma ovarii is an uncommon ovarian teratoma comprised predominantly of mature thyroid tissue. The combination of pseudo-Meigs' syndrome, and elevation of CA 125 to the struma ovarii is a rare condition that can mimic ovarian malignancy. We reported a case of benign struma ovarii, presenting with the clinical features of advanced ovarian carcinoma: complex pelvic mass, gross ascites, bilateral pleural effusion and markedly elevated serum CA 125 levels. The patient underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Ascites and pleural effusion were not evident and the CA 125 levels returned to normal following surgical excision. A systematic review of reported cases of coexistent benign struma ovarii, pseudo-Meigs' syndrome and elevated serum CA 125 was performed. Struma ovarii accompanied by pseudo-Meigs' syndrome and elevated serum CA 125 should be considered in the differential diagnosis of ovarian epithelial cancer.

[Influences of active immunotherapy on T helper cell type 1 and 2 cytokines in women with unexplained habitual abortion].

OBJECTIVE: To investigate the influences of active immunotherapy on T helper cell (Th)1/Th2 type cytokines in women with unexplained habitual abortion (UHA). METHODS: A total of 55 patients with UHA were studied, including 30 cases after active immunotherapy (AIT) and 25 cases without any therapy (NAIT). Fifteen cases of normal nonpregnant (NNP) women were selected as control group. Supernatants from trophoblast-activated peripheral blood mononuclear cells (PBMC) of the three groups were tested by enzyme-linked immunosorbent assay (ELISA) for interferon gamma (IFN-gamma), interleukin-2 (IL-2), IL-4, IL-10. RESULTS: (1) The levels of IL-2 and IFN-gamma in AIT group [(108 +/- 37) ng/L and (110 +/- 52) ng/L, respectively] were lower significantly than those in NAIT group [(223 +/- 85) ng/L and (326 +/- 92) ng/L, respectively] (P < 0.05). The levels of IL-4 and IL-10 in AIT group [(50 +/- 11) ng/L and (140 +/- 37) ng/L, respectively] were higher than those in NAIT group [(23 +/- 11) ng/L and (52 +/- 28) ng/L] +/- (P < 0.05). The levels of IL-2 and IFN-gamma in NAIT group were higher than those in NNP group [(92 +/- 32) ng/L and (102 +/- 35) ng/L] (P < 0.05). The levels of IL-4 and IL-10 in NAIT group were lower than those in NNP group [(62 +/- 21) ng/L and (150 +/- 42) ng/L] (P < 0.05). The level of every cytokine had no difference in AIT group and NNP group (P > 0.05). (2) Twenty-six women in AIT group got pregnant, but 8 women experienced pregnancy loss repeatedly whose IL-2, IFN-gamma levels were higher than those in other 18 women got successful pregnancy and IL-4, IL-10 levels lower than the latter. CONCLUSIONS: UHA patients have Th1 type immunity to trophoblast and produce high-level Th1 type cytokines which probably result in pregnancy loss. Active immunotherapy could make a shift from Th1 to Th2 immunity, thus favoring the maintenance of pregnancy.

Conservative management of endometrial stromal sarcoma at stage III: A case report.

Endometrial stromal sarcoma (ESS) is a rare malignant tumor of the uterus. The standard treatment is surgery, such as total hysterectomy with bilateral salpingo-oophorectomy. The use of adjuvant treatment, including chemotherapy, radiation therapy and endocrine therapy, remains controversial, so it is uncommon for conservative management to be performed in patients with low-grade ESS. The present study reports the case of a 19-year-old female with ESS at stage III who underwent a local mass resection by laparoscopic surgery. A high dose of progestin (medroxyprogesterone acetate) therapy was then administered. Conservative management resulted in complete remission of the low-grade ESS, with no sign of recurrence at the 33-month follow-up.

Successful pregnancy following conservative management of low-grade endometrial stromal sarcoma: A case report.

It is uncommon that fertility is preserved in young nulliparous females with low-grade endometrial stromal sarcoma (ESS). Therefore, successful pregnancy following such conservative management has been rarely reported in previous literature. A 25-year-old female (gravida, 0; para, 0) underwent hysteroscopic surgery and was pathologically diagnosed with an endometrial stromal nodule. The patient underwent fertility-preserving local resection and uterine reconstruction, with a final pathological diagnosis of low-grade ESS. Endocrine therapy was then administered. Conservative management resulted in the complete remission of low-grade ESS. The patient naturally conceived and successfully delivered a healthy baby at 42 weeks' gestation by cesarean section, ~30 months following diagnosis with low-grade ESS. In conclusion, conservative management, including fertility-preserving local mass resection and endocrine therapy, can be effective for low-grade ESS and may yield a favorable outcome for young nulliparous females desiring fertility preservation.