Efficacy and Safety of Platinum-Based Chemotherapy for Ovarian Cancer During Pregnancy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Based on the available data on ovarian cancer during pregnancy, we performed a review and meta-analysis to evaluate the efficacy and safety of platinum-based chemotherapy against ovarian cancer during pregnancy. METHODS: We systematically searched three databases including the PubMed, Embase, and Cochrane Library databases for articles published from January 1986 to December 2020 using the following terms: "ovarian tumors OR ovarian carcinoma OR adnexal masses OR ovarian cancer" AND "pregnancy" AND "chemotherapy." Two authors (Yaping Pei and Yuanfeng Gou) independently searched the literature and extracted data from each eligible study. The outcome measures were overall survival (OS) and progression-free survival (PFS). The OS and PFS of all patients were estimated by Kaplan-Meier survival curves and log-rank tests. RESULTS: A total of 43 studies including 55 cases of ovarian cancer during pregnancy were selected. Forty-eight patients were comprehensively staged using the International Federation of Gynecology and Obstetrics (FIGO) staging system. Twenty-six of the 48 patients (54.17%) were diagnosed with early-stage disease, while the remaining had advanced stages (II, III, and IV). The mean age at diagnosis was 29.31 years. The majority of patients in this meta-analysis were diagnosed at a mean gestational age of 16.05 weeks. The mean GA at chemotherapy administration was 17.42 weeks. Overall, 55 women gave birth to 56 newborns, including a pair of twins. At the end of follow-up (median 10 months, range 0-73 months), all the children were healthy, except for one child who died 5 days after delivery due to a congenital abnormality. During 2-204 months of follow-up, there were five cases of recurrence, with no evidence of recurrence in the remaining cases. Unfortunately, one patient died 29 months after diagnosis. Neither median overall survival nor median progression-free survival was obtained. CONCLUSION: Platinum-based chemotherapy may be a good choice for pregnant women with ovarian cancer who want to continue their pregnancy.

ENO1 monoclonal antibody inhibits invasion, proliferation and clone formation of cervical cancer cells.

α-enolase (ENO1), highly expressing in cell membranes, cytoplasm and nuclei of cervical cancer and other tumors, acts as a plasminogen receptor and a glycolytic enzyme. ENO1 is found to be associated with tumorigenesis, invasion and migration, and proves to be an ideal target of tumor therapy. In this study, ENO1 monoclonal antibodies (ENO1mAb) was prepared to blockade ENO1 and the therapeutic role was observed in cervical cancer cells. First, ENO1mAb was prepared and screened by evaluating the inhibitory effect on migration and invasion of cervical cancer cells, which is supposed to block ENO1 expressed on cell membrane. Second, folic acid (FA) conjugated PLGA nanoparticles (FA-SS-PLGA) targeting tumor cells were prepared to mediate ENO1mAb entry into cells and its anti-tumor effects were investigated in vitro. We found that PLGA/FA-SS-PLGA nanoparticles-mediated ENO1mAb could antagonize the activity of ENO1 enzyme, significantly decreased the contents of lactic acid and pyruvate, and inhibited the proliferation, migration and clone formation of cervical cancer cells compared with the sham control (P < 0.05). In summary, ENO1mAb could specifically block ENO1 expressed on cell membrane and inhibit ENO1 glycolysis enzyme activity inside tumor cells, and plays a therapeutic role against cervical cancer cells. It suggests that ENO1mAb has promising anti-tumor effects.

Oxymatrine Liposomes for Intervertebral Disc Treatment: Formulation, in vitro and vivo Assessments.

PURPOSE: Intervertebral disc degeneration (IVDD) is the main cause of modern low back pain, leading to high societal economic costs. To find an effective medical treatment for this disease, oxymatrine liposomes (OMT-LIP) were prepared with the pH-gradient method. MATERIALS AND METHODS: Nucleus pulposus (NP) cells from Sprague-Dawley rats were used for the cell experiments. Kunming mice were used for in vivo imaging. LIP were employed to deliver OMT, and the particle size, ζ-potential, morphology, in vitro stability and in vitro release characteristics were evaluated. The OMT-LIP targeting effect was measured by in vivo imaging. Cell Counting Kit-8 assays were used to detect the cytotoxicity of OMT and OMT-LIP on NP cells. Therapeutic efficacy was measured by Western blot, real-time quantitative polymerase chain reaction, and apoptosis assays. Radiologic analysis was performed to evaluate the therapeutic effects in vivo. RESULTS: Orthogonal test results revealed that the mass ratio of egg yolk phosphatidylcholine to cholesterol was the key factor to effectively trap OMT in LIP. Optimal OMT-LIP showed multivesicular structure with entrapment efficiency of 73.4 ± 4.1%, particle size of 178.1 ± 2.9 nm, and ζ-potential of -13.30 ± 2.34 mV. OMT-LIP manifested excellent stability in vitro and presented significantly longer sustained release compared to OMT solution in phosphate-buffered saline (pH 7.4). OMT-LIP conspicuously increased OMT accumulation in the degenerative disc, attenuated NP cell apoptosis, reduced the expression of matrix metalloproteinases 3/9 and interleukin-6, and decreased degradation of type II collagen. In in vivo study, X-ray demonstrated that OMT-LIP inhibited IVDD. CONCLUSION: OMT-LIP may be a useful treatment to alleviate disc inflammation and IVDD.

ICAM5 as a Novel Target for Treating Cognitive Impairment in Fragile X Syndrome.

Fragile X syndrome (FXS) is the most common inherited form of intellectual disability, resulted from the silencing of the Fmr1 gene and the subsequent loss of fragile X mental retardation protein (FMRP). Spine dysgenesis and cognitive impairment have been extensively characterized in FXS; however, the underlying mechanism remains poorly understood. As an important regulator of spine maturation, intercellular adhesion molecule 5 (ICAM5) mRNA may be one of the targets of FMRP and involved in cognitive impairment in FXS. Here we show that in Fmr1 KO male mice, ICAM5 was excessively expressed during the late developmental stage, and its expression was negatively correlated with the expression of FMRP and positively related with the morphological abnormalities of dendritic spines. While in vitro reduction of ICAM5 normalized dendritic spine abnormalities in Fmr1 KO neurons, and in vivo knockdown of ICAM5 in the dentate gyrus rescued the impaired spatial and fear memory and anxiety-like behaviors in Fmr1 KO mice, through both granule cell and mossy cell with a relative rate of 1.32 ± 0.15. Furthermore, biochemical analyses showed direct binding of FMRP with ICAM5 mRNA, to the coding sequence of ICAM5 mRNA. Together, our study suggests that ICAM5 is one of the targets of FMRP and is implicated in the molecular pathogenesis of FXS. ICAM5 could be a therapeutic target for treating cognitive impairment in FXS.SIGNIFICANCE STATEMENT Fragile X syndrome (FXS) is characterized by dendritic spine dysgenesis and cognitive dysfunctions, while one of the FMRP latent targets, ICAM5, is well established for contributing both spine maturation and learning performance. In this study, we examined the potential link between ICAM5 mRNA and FMRP in FXS, and further investigated the molecular details and pathological consequences of ICAM5 overexpression. Our results indicate a critical role of ICAM5 in spine maturation and cognitive impairment in FXS and suggest that ICAM5 is a potential molecular target for the development of medication against FXS.

Calsyntenin-1 Negatively Regulates ICAM5 Accumulation in Postsynaptic Membrane and Influences Dendritic Spine Maturation in a Mouse Model of Fragile X Syndrome.

Fragile X syndrome (FXS) is a neurodevelopmental disorder that causes intellectual disability, as well as the leading monogenic cause of autism spectrum disorders (ASD), in which neurons show aberrant dendritic spine structure. The reduction/absence of the functional FMRP protein, coded by the X-linked Fmr1 gene in humans, is responsible for the syndrome. Targets of FMRP, CLSTN1, and ICAM5, play critical roles in the maturation of dendritic spines, synapse formation and synaptic plasticity. However, the implication of CLSTN1 and ICAM5 in dendritic spine abnormalities and the underlying neuropathologic processes in FXS remain uninvestigated. In this study, we demonstrated that CLSTN1 co-localizes and co-transports with ICAM5 in cultured cortical neurons. Also we showed that shRNA-mediated downregulation of CLSTN1 in cultured WT neurons increases ICAM5 on the surface of synaptic membrane, subsequently affecting the maturation of dendritic spines. Whereas, normalization of CLSTN1 level in Fmr1 KO neurons reduces ICAM5 abundance and rescues impaired dendritic spine phenotypes. Most importantly, CLSTN1 protein is reduced in the postnatal medial prefrontal cortex of Fmr1 KO mice, which is correlated with increased ICAM5 levels on the surface of synapses and excessive filopodia-like spines. In conclusion, this study demonstrates that CLSTN1 plays a critical role in dendritic spine formation and maturation in FXS by regulating ICAM5 redistribution.

Effects of partial desulfation on antioxidant and inhibition of DLD cancer cell of Ulva fasciata polysaccharide.

Ulva fasciata belonging to the family Ulvaceae, commonly known as 'sea lettuce', is an abundantly growing green seaweed in coastal seashore of South China. Three different molecular weight sulfated polysaccharides (UFP1, UFP2 and UFP3) were extracted and separated from U. fasciata by hot water extraction and ultrafiltration. The three native UFP fractions had partial desulfurization by solvolytic desulfation respectively and the effect of sulfate content on the exhibition of the antioxidant and anti-tumor capacities had been evaluated and compared. The results showed that each native polysaccharide (UFP1, UFP2, UFP3) with high sulfate content exhibited better antioxidant activities compared with the partial desulfated polysaccharides (DS-UFP1, DS-UFP2, DS-UFP3). Specifically, UFP2 with relatively high sulfate content, molecular weight and uronic acid content had consistently excellent antioxidant performances. However, UFP2 demonstrated the minimal inhibitory effects on growth of DLD intestinal cancer cells. Instead, DS-UFP3 with the lowest sulfate content but highest uronic acid content and molecular weight exhibited the best antitumor activity.

In intro antioxidant activities of different sulfated polysaccharides from chlorophytan seaweeds Ulva fasciata.

Four different molecular weight sulfated polysaccharides (UFP1, UFP2, UFP3 and UFP4) were extracted and separated from Ulva fasciata by hot water extraction and ultrafiltration. Their chemical and physical characteristics were determined and antioxidant activities were investigated on the basis of superoxide radical assay, hydroxyl radical assay, ABTS radical assay, and reducing power assay. The results showed that four polysaccharides exhibited antioxidant properties, and UFP2 and UFP3, which have lower content of sulfate showed higher antioxidant activities than UFP1 and UFP4, which have higher content of sulfate. Besides, the content of protein, uronic acid and molecular weights of polysaccharides also influence their antioxidant activities. The antioxidant activities of UFP were not a function of a single factor but a combination of several factors.