Operation for locally advanced cervical cancer after concurrent chemoradiotherapy.

OBJECTIVE: This paper aimed to discuss the scope of operation and clinical effects for locally advanced cervical cancer (LACC) after concurrent chemoradiotherapy (CCRT). METHODS: We retrospectively reviewed the records of 444 patients with stages IB2-IIB cervical cancer who were divided into two groups whether or not they received CCRT before radical operation in our institute from January 2013 to December 2016. Patients' characteristics, treatments, and outcomes were analyzed. RESULTS: The total efficiency (CR + PR) of the CCRT + operation group was 96.2%. Specifically, the CR rate was 9.1%, and the PR rate was 87.1%. The positive rates of cervical deep interstitial infiltration, lymphatic metastasis, and lymphangial infiltration of the operation group were significantly higher than those of the CCRT + operation group (P < 0.05). A total of 24 and 162 patients in the CCRT + operation group and the operation group, respectively, received adjuvant therapy (P < 0.05). The incidence rate of edema of the lower extremity, radiation enteritis, and radiocystitis after postoperative adjuvant radiotherapy in the operation group was significantly higher than that of the CCRT + operation group (P < 0.05). The 5-year survival rates and 5-year progression-free survival (PFS) rates of the CCRT + operation and operation groups were 79.3% versus 64.0% and 68.9% versus 45.2%, respectively (P < 0.05). CONCLUSIONS: Comprehensive treatment that combines CCRT and radical operation to LACC achieves satisfying clinical effects without increasing the occurrence rate of intraoperative and postoperative complications. Moreover, such treatment can improve the 5-year PFS rate and OS rate.

Clinicopathologic characteristics and prognostic factors of patients with surgically treated high-grade neuroendocrine carcinoma of the cervix: A multicenter retrospective study.

OBJECTIVE: To evaluate the prognostic factors and survival outcomes of patients with surgically treated high-grade neuroendocrine carcinoma of the cervix (NECC). METHODS: This multicenter, retrospective study involved 98 cervical cancer patients with stage IA2-IIA2 and IIIC1/2p high-grade NECC. We divided the patients into two groups based on histology: the pure and mixed groups. All clinicopathologic variables were retrospectively evaluated. Cox regression and Kaplan-Meier methods were used for analysis. RESULTS: In our study, 60 patients were in the pure group and 38 patients were in the mixed group. Cox multivariate analysis showed that mixed histology was a protective factor impacting overall survival (OS) (P = 0.026) and progression free survival (PFS) (P = 0.018) in surgically treated high-grade NECC. Conversely, survival outcomes were negatively impacted by ovarian preservation (OS: HR, 20.84; 95% CI: 5.02-86.57, P < 0.001), age >45 years (OS: HR, 4.50; 95% CI: 1.0-18.83, P = 0.039), tumor size >4 cm (OS: HR, 6.23; 95% CI: 2.34-16.61, P < 0.001), parity >3 (OS: HR, 4.50; 95% CI: 1.02-19.91, P = 0.048), and perineural invasion (OS: HR, 5.21; 95% CI: 1.20-22.53, P = 0.027). Kaplan-Meier survival curves revealed notable differences in histologic type (OS: P = 0.045; PFS: P = 0.024), chemotherapy (OS: P = 0.0056; PFS: P = 0.0041), ovarian preservation (OS: P = 0.00031; PFS: P = 0.0023), uterine invasion (OS: P < 0.0001; PFS: P < 0.0001), and depth of stromal invasion (OS: P = 0.043; PFS: P = 0.022). CONCLUSION: Patients with mixed histologic types who undergo surgery for high-grade NECC have a better prognosis. Meanwhile, ovarian preservation, tumor size >4 cm, parity >3, age >45 years and perineural invasion were poor prognostic predictors. Therefore, patients with high-risk factors should be considered in clinical practice.

Stromal cell-derived factor-1 (SDF-1) enhances cells invasion by αvß6 integrin-mediated signaling in ovarian cancer.

Ovarian carcinoma is a common gynecological malignancy and a great threat to health as a result of metastasis. The chemokine stromal-derived factor (SDF-1) plays multiple roles in tumor pathogenesis. However, the precise molecular mechanism underlying SDF-1-induced ovarian cancer cell invasion is still undefined. αvß6 integrin is an important factor in tumor progression. Therefore, we speculate that SDF-1-enhanced ovarian cancer cell invasion is related to αvß6 integrin-mediated signaling. After culturing with SDF-1, an obvious time- and dose-dependent increase in αvß6 integrin was demonstrated. Furthermore, CXC receptor 4 (CXCR4) was responsible for SDF-1-induced αvß6 integrin expression. Simultaneously, SDF-1 was found to dramatically enhance extracellular matrix degradation via urokinase-type plasminogen activator (uPA) expression and cell invasion by αvß6 integrin expression; these reinforce failed to be increased when pretreatment was performed with the CXCR4 inhibitor AMD3100 or anti-αvß6 integrin antibody, respectively. In addition, αvß6 integrin induced the phosphorylation of p38 MAPK and PI3 K/Akt, contributing to the up-regulation of uPA, as treatment with the specific inhibitor for p38 mitogen-activated protein kinases (MAPK) (SB203580) or phosphatidylinositol 3-kinase (PI3 K)/Akt (LY294002) strikingly abrogated uPA expression. Taken together, these results demonstrated that SDF-1 enhanced ovarian cancer cell invasion through αvß6 integrin-mediated uPA expression via the p38 MAPK and PI3 K/Akt pathway. Consequently, our findings will provide a new explanation about how SDF-1 aggravates the pathogenesis of ovarian cancer.

Uterine packing during cesarean section in the management of intractable hemorrhage in central placenta previa.

OBJECTIVE: To determine the safety and effectiveness of uterine packing in the management of intractable hemorrhage during cesarean section for central placenta previa. METHODS: This retrospective study was conducted on 70 pregnant women with central placenta previa from May 2005 to March 2010. Patients with uterine packing in the control of massive hemorrhage during cesarean section were identified. The indications, uterine packing procedures, estimated blood loss, postoperative complications, and packing material used were reviewed. RESULTS: A total of 70 patients were identified among 1,121 women with placenta previa during the study period. Sixty-five cases were successful in the control of intraoperative bleeding using uterine packing. Two patients with severe placenta accreta had hemorrhage during cesarean section, and packing with gauze in the uterine cavity was not able to control the bleeding, thereby resulting in cesarean hysterectomy. One case demonstrated failure in packing because of disseminated intravascular coagulation occurring before hospital admission. The remaining two patients had massive vaginal bleeding after uterine packing in cesarean section and underwent laparotomy or hysterectomy 4 h postoperative. CONCLUSION: Uterine packing is a safe and effective technique in the control of intractable hemorrhage in cesarean section. It is a reasonable alternative to further surgical intervention in patients with intractable obstetric hemorrhage, especially in developing countries.

Artificial Intelligence Algorithm-Based Computerized Tomography Image Features Combined with Serum Tumor Markers for Diagnosis of Pancreatic Cancer.

The objective of this study was to analyze the value of artificial intelligence algorithm-based computerized tomography (CT) image combined with serum tumor markers for diagnoses of pancreatic cancer. In the study, 68 hospitalized patients with pancreatic cancer were selected as the experimental group, and 68 hospitalized patients with chronic pancreatitis were selected as the control group, all underwent CT imaging. An image segmentation algorithm on account of two-dimensional (2D)-three-dimensional (3D) convolution neural network (CNN) was proposed. It also introduced full convolutional network (FCN) and UNet network algorithm. The diagnostic performance of CT, serum carbohydrate antigen-50 (CA-50), serum carbohydrate antigen-199 (CA-199), serum carbohydrate antigen-242 (CA-242), combined detection of tumor markers, and CT-combined tumor marker testing (CT-STUM) for pancreatic cancer were compared and analyzed. The results showed that the average Dice coefficient of 2D-3D training was 84.27%, which was higher than that of 2D and 3D CNNs. During the test, the maximum and average Dice coefficient of the 2D-3D CNN algorithm was 90.75% and 84.32%, respectively, which were higher than the other two algorithms, and the differences were statistically significant (P < 0.05). The penetration ratio of pancreatic duct in the experimental group was lower than that in the control group, the rest were higher than that in the control group, and the differences were statistically significant (P < 0.05). CA-50, CA-199, and CA-242 in the experimental group were 141.72 U/mL, 1548.24 U/mL, and 83.65 U/mL, respectively, which were higher than those in the control group, and the differences were statistically significant (P < 0.05). The sensitivity, specificity, positive predictive value, and authenticity of combined detection of serum tumor markers were higher than those of CA-50, CA-199, and CA-242, and the differences were statistically significant (P < 0.05). The results showed that the proposed algorithm 2D-3D CNN had good stability and image segmentation performance. CT-STUM had high sensitivity and specificity in diagnoses of pancreatic cancer.

Pregnancy complicating systemic lupus erythematosus: a series of 86 cases.

OBJECTIVE: To investigate the timing of pregnancy and pregnancy termination and its management in women with pregnancy complicating systemic lupus erythematosus (SLE). METHODS: A series of 86 cases of pregnancy complicating SLE treated in our hospital from January 2005 to June 2010 were retrospectively reviewed, including 54 cases of planned pregnancy and 32 cases of unplanned pregnancy. The pregnancy courses and clinical outcomes were analyzed. RESULTS: While 12 patients in planned pregnancy group showed active SLE during pregnancy, all 32 patients in the unplanned pregnancy group presented severe SLE complications. The incidences of pregnancy loss, preterm delivery and neonatal asphyxia in the unplanned pregnancy group were significantly higher than planned pregnancy group (P < 0.05), and the infant body weight was lower in the unplanned pregnancy group (P < 0.05). A total of 78 live infants were born and no mortality was reported, including 15 preterm infants and one neonatal SLE. CONCLUSION: Planned pregnancy during stable stage, appropriate treatment in pregnancy and close monitoring can improve the security of pregnancy complicating SLE. In situations that the drug treatment is ineffective and the mother and infant are threatened, or the fetus is mature, the pregnancy should be terminated promptly, thereby reducing the complications, and increasing the success rate of pregnancy and perinatal survival rate.

Repeated medical abortions and the risk of preterm birth in the subsequent pregnancy.

PURPOSE: The aim of this study was to determine the impact of repeated first trimester mifepristone-induced medical abortions on the risk of preterm birth in a subsequent pregnancy. METHODS: This is a pregnancy-based cohort study. Clinical data were collected from seven public hospitals in Chengdu, China from January 2006 to December 2009. Pregnant women with one or more first trimester mifepristone-induced medical abortions, and/or one or more surgical abortions, or no previous induced abortions were included in the study. The women were monitored through pregnancy and birth. Samples for analysis included 18,024 singleton births. RESULTS: The risk of preterm birth among women with one or more first trimester mifepristone-induced abortions did not differ significantly from the risk among primigravida women (OR 1.03, 95% confidence interval 0.53-1.63). The risks of preterm birth were higher among women with repeated surgical abortions in comparison to women with repeated medical abortions (OR 1.22, 95% confidence interval 1.03-1.64). CONCLUSIONS: A history of multiple first trimester mifepristone-induced abortions is not associated with a higher risk of preterm delivery among singleton births in the first subsequent pregnancy.

Dysbindin facilitates invasion and metastasis by promoting phosphorylation of ERK in epithelial ovarian cancer.

Dysbindin has been reported to be correlated with several malignancies. However, the clinical significance and biological role of dysbindin in epithelial ovarian cancer remains largely unknown. Here we demonstrated that the mRNA and protein levels of dysbindin were significantly upregulated in EOC tissues compared with normal ovarian tissues. High levels of dysbindin were significantly correlated with worse clinicopathological characteristics and poor prognosis in EOC patients. Overexpression and silencing of dysbindin promoted and inhibited, respectively, invasion and metastasis of EOC cells in vitro and in vivo. Mechanistically, dysbindin activates phosphorylation of ERK to promote the epithelial-mesenchymal transition and to mediate the invasive and metastatic ability of EOC cells. Our findings suggest that dysbindin facilitates invasion and metastasis by promoting the EMT of EOC cells and may serve as a potential therapeutic target in EOC.

CDK4/6 inhibition promotes immune infiltration in ovarian cancer and synergizes with PD-1 blockade in a B cell-dependent manner.

Great progress has been made in the field of tumor immunotherapy in the past decade. However, the therapeutic effects of immune checkpoint blockade (ICB) against ovarian cancer are still limited. Recently, an inhibitor of cyclin-dependent kinases 4 and 6 (CDK4/6i) has been reported to enhance antitumor immunity in preclinical models. The combined use of CDK4/6i and ICB may be beneficial, but the effects of CDK4/6is on the tumor immune microenvironment and whether they can synergize with ICB in treating ovarian cancer remain unknown. Methods: In this study, we first assessed the antitumor efficacy of abemaciclib, an FDA-approved CDK4/6i, in a syngeneic murine ovarian cancer model. Then, immunohistochemistry, immunofluorescence and flow cytometry were performed to evaluate the number, proportion, and activity of tumor-infiltrating lymphocytes. Cytokine and chemokine production was detected both in vivo and in vitro by PCR array analysis and cytokine antibody arrays. The treatment efficacy of combined abemaciclib and anti-PD-1 therapy was evaluated in vivo, and CD8+ and CD4+ T cell activities were analyzed using flow cytometry. Lastly, the requirement for both CD8+ T cells and B cells in combination treatment was evaluated in vivo, and potential cellular mechanisms were further analyzed by flow cytometry. Results: We observed that abemaciclib monotherapy could enhance immune infiltration, especially CD8+ T cell and B cell infiltration, in the ID8 murine ovarian cancer model. Immunophenotyping analysis showed that abemaciclib induced a proinflammatory immune response in the tumor microenvironment. PCR array analysis suggested the presence of a Th1-polarized cytokine profile in abemaciclib-treated ID8 tumors. In vitro studies showed that abemaciclib-treated ID8 cells secreted more CXCL10 and CXCL13, thus recruiting more lymphocytes than control groups. Combination treatment achieved better tumor control than monotherapy, and the activities of CD8+ and CD4+ T cells were further enhanced when compared with monotherapy. The synergistic antitumor effects of combined abemaciclib and anti-PD-1 therapy depended on both CD8+ T cells and B cells. Conclusion: These findings suggest that combined treatment with CDK4/6i and anti-PD-1 antibody could improve the efficacy of anti-PD-1 therapy and hold great promise for the treatment of poorly immune-infiltrated ovarian cancer.

SDF-1/CXCR4 axis facilitates myeloid-derived suppressor cells accumulation in osteosarcoma microenvironment and blunts the response to anti-PD-1 therapy.

Immune checkpoint inhibitors, such as anti-PD-1/PD-L1, are a novel class of inhibitors that function as a tumor suppressing factor via modulation of immune cell-tumor cell interaction. To date, PD-1/PD-L1 inhibitors have been approved for the treatment of specific types of tumors and obtained good clinical efficacy. However, patients with osteosarcoma showed poor response to anti-PD-1/PD-L1 therapy, the mechanism of which is not well understood. In this study, we found that osteosarcoma tissues were heavily infiltrated by myeloid-derived suppressor cells (MDSCs) which could inhibit cytotoxicity T cell (CTL) expansion. Further study revealed that the vast majority of tumor-infiltrating MDSCs were CXCR4 positive and could migrate toward an SDF-1 gradient. The binding of SDF-1 to its receptor CXCR4 results in the activation of downstream AKT pathway that mediates reduced apoptosis of MDSCs. We also demonstrated that AMD3100, a CXCR4 antagonist, has a synergistic effect with anti-PD-1 antibody in tumor treatment in a murine model of osteosarcoma. These findings provide the basis for establishing CXCR4 antagonist and PD-1/PD-L1 inhibitors co-administration as a novel therapeutic regimen for patients with osteosarcoma and hold great promise for improving the therapeutic effect of osteosarcoma.

Desferrioxamine decreases NAD redox potential of intact red blood cells: evidence for desferrioxamine as an inducer of oxidant stress in red blood cells.

BACKGROUND: Desferrioxamine (DFO) is an important iron chelating agent. It has also been thought of as an agent with anti-oxidant potential as it chelates ferric iron in various parts of the body. However, there is evidence suggesting that it may paradoxically affect red blood cells (RBC) by inducing intracellular oxidant stress. To further understand the mechanism of DFO's interaction with RBC, we conducted a study to determine the effect of DFO upon RBC's redox status. METHODS: We examined NAD redox potential in intact RBC (N = 5) incubated with DFO. RBC were incubated with 6 mM DFO for 2 hours. RESULTS: Significant decreases in NAD redox potential were observed after incubation of RBC with 6 mM DFO. The mean decrease was 10.01 PlusMinus; 1.98% (p < 0.0004). CONCLUSIONS: The data confirm the oxidant effect of DFO on RBC.

SDF-1/CXCR7 axis enhances ovarian cancer cell invasion by MMP-9 expression through p38 MAPK pathway.

Ovarian cancer is an aggressive gynecological malignancy with high metastatic potential. Recently, the CXC receptor (CXCR7) has been identified as a new receptor for stromal-derived factor-1 (SDF-1), and exerts important roles in cancer development. However, its effect on ovarian cancer and the underlying mechanism remain unknown. In this study, we detected abundant CXCR7 expression in ovarian cancer tissues and cells. Moreover, SDF-1 induced dramatically upregulation of CXCR7 mRNA and protein levels, indicating that the SDF-1/CXCR7 axis existed in ovarian cancer. Further analysis confirmed that SDF-1 enhanced cell adhesion and subsequent invasion, which were significantly attenuated when pretreated with CXCR7 small interference RNA (siRNA), indicating the critical function of SDF-1/CXCR7 in cell invasion. Further mechanistic analysis indicated that SDF-1/CXCR7 enhanced cell invasion by matrix metalloproteinase (MMP)-9, as pretreatment with MMP-9 siRNA significantly abrogated a number of invading cells. Additionally, SDF-1/CXCR7 induced phosphorylation of the p38 MAPK pathway, which was accounted for MMP-9 expression as preconditioning with the p38 MAPK inhibitor SB203580 obviously decreased MMP-9 expression. Together, our data implied that SDF-1/CXCR7 enhanced ovarian cancer cell invasion by MMP-9 expression through the p38 MAPK pathway. Thus, these findings confirmed the critical role of SDF-1/CXCR7 during the pathological processes of ovarian cancer and supported its potential targets for further development of antiovarian cancer therapy.