Deciphering the ovarian cancer ascites fluid peptidome

Background

Conventional proteomic approaches have thus far been unable to identify novel serum biomarkers for ovarian cancer that are more sensitive and specific than the current clinically used marker, CA-125. Because endogenous peptides are smaller and may enter the circulation more easily than proteins, a focus on the low-molecular-weight region may reveal novel biomarkers with enhanced sensitivity and specificity. In this study, we deciphered the peptidome of ascites fluid from 3 ovarian cancer patients and 3 benign individuals (ascites fluid from patients with liver cirrhosis).

Results

Following ultrafiltration of the ascites fluids to remove larger proteins, each filtrate was subjected to solid phase extraction and fractionated using strong cation exchange chromatography. The resultant fractions were analyzed using an Orbitrap mass spectrometer. We identified over 2000 unique endogenous peptides derived from 259 proteins. We then catalogued over 777 peptides that were found only in ovarian cancer ascites. Our list of peptides found in ovarian cancer specimens includes fragments derived from the proteins vitronectin, transketolase and haptoglobin.

Conclusions

Peptidomics may uncover previously undiscovered disease-specific endogenous peptides that warrant further investigation as biomarkers for ovarian cancer.     

Fertile heteroallelic combinations of mutant alleles of the otu locus of Drosophila melanogaster

Summary This paper describes the ovarian pathologies observed when 108 different heteroallelic combinations were made involving 17 independent mutations at the ovarian tumor (otu) locus. Most of the mutant phenotypes can be explained as graded responses by individual germ cells to different levels of functionally active otu gene product (OGP) synthesized by the mutant cells themselves. The lowest and highest levels of OGP appear to be produced by otu ¹⁰ and otu ¹⁴, respectively. In most heteroallelic ovaries the alleles have additive effects, and hybrid germ cells reach a developmental stage more advanced than the weaker homozygote but less advanced than the stronger homozygote. However, examples of both positive and negative complementation also have been found, and these suggest that the products encoded by different mutant alleles can combine to form dimers or multimers which may be superior or inferior to the homodimers. In flies homozygous for otu ¹¹ most ovarioles contain tumors, but some germ cells are able to develop further than those in otu ¹⁴ homozygotes. This suggests that, while otu ¹¹ produces intermediate levels of OGP, it also produces a second product (which otu ¹⁴ cannot make) that is utilized at the period in oogenesis when development in cells homozygous for otu ¹⁴ is blocked. When otu ¹¹ is combined with any one of eight specific alleles, it allows oocyte/nurse cell syncytia to differentiate that can complete development and undergo embryogenesis, if fertilized. The endopolyploid nurse cells of these hybrids have giant polytene chromosomes, and the presence of GPCs in functionally active, germ-line derived cells provides an interesting new system for experimental study. Analysis of the characteristic ovarian pathologies produced by flies of different genotypes leads to the conclusion that the products of the otu ⁺ gene are utilized during at least six different periods in Drosophila oogenesis.     

Ovarian steroids and serotonin neural function

The serotonin neural system originates from ten nuclei in the mid- and hindbrain regions. The cells of the rostral nuclei project to almost every area of the forebrain, including the hypothalamus, limbic regions, basal ganglia, thalamic nuclei, and cortex. The caudal nuclei project to the spinal cord and interact with numerous autonomic and sensory systems. This article reviews much of the available literature from basic research and relevant clinical research that indicates that ovarian steroid hormones, estrogens and progestins, affect the function of the serotonin neural system. Experimental results in nonhuman primates from this laboratory are contrasted with studies in rodents and humans. The sites of action of ovarian hormones on the serotonin neural system include effects within serotonin neurons as well as effects on serotonin afferent neurons and serotonin target neurons. Therefore, information on estrogen and progestin receptor-containing neurons was synthesized with information on serotonin afferent and efferent circuits. The ability of estrogens and progestins to alter the function of the serotonin neural system at various levels provides a cellular mechanism whereby ovarian hormones can impact mood, cognition, pain, and numerous other autonomic functions.     

TEP au 18-FDG et carcinose péritonéale d’origine ovarienne : valeurs diagnostique et pronostique avant chimio-hyperthermie intra-péritonéale (CHIP)

AimEvaluate 18-FDG PET/CT diagnostic and prognostic value before HIPEC.Materials and methodsThis retrospective monocentric study included 38 patients with recurrent (n = 27) or primary (n = 11) ovarian cancer who were blinded reviewed for the presence of peritoneal lesions on PET/CT before HIPEC treatment. The results were compared to surgical and histopathological findings, and to survival curves.ResultsThirty-two patients had peritoneal carcinomatosis based on surgical and histopathological findings, and 19 based on PET. There was no suspicious site of abnormal FGD uptake in the supradiaphragmatic regions. The sensitivity and specificity were respectively 56.2 and 100%. Among the 14 false negative patients, 11 had infracentimetric peritoneal implants, and most of them (n = 13) had chemotherapy before HIPEC. There was significantly more patients treated by chemotherapy in the negative PET group (P = 0.02). Even if the event rate observed was higher in the positive PET group for both event free and overall survival (respectively 68% vs. 64% and 26.3% vs. 17.6%), no significant difference was observed using the survival curves (respectively P = 0.62 and 0.59).ConclusionFDG PET/CT before HIPEC showed excellent specificity and lower sensitivity, due to small peritoneal implants and probably to chemotherapy before HIPEC. No significant prognostic value of FDG PET was observed in our study. FDG PET could be considered as a useful tool for detecting distant metastasis with an impact on therapeutic management.     

N-三甲基壳聚糖包裹喜树碱治疗卵巢癌淋巴结转移的研究

目的:采用N-三甲基壳聚糖包裹喜树碱(CPT-TMC)以增加其水溶性,并检测其抑制卵巢癌细胞淋巴结转移的效应。方法:体外实验,PI染色检测CPT-TMC促肿瘤细胞凋亡作用,体内实验,荷瘤裸鼠随机分为4组(5只/组):NS组、TMC组、CPT组及CPT-TMC组,通过尾静脉给药,每周2次,持续3周,Evan's Blue Dye染色,显影腹腔肿大转移的淋巴结。结果:PI染色提示CPT-TMC显著促进肿瘤细胞凋亡(P0.05);Evan's Blue Dye显影显示CPT-TMC显著抑制肿瘤细胞淋巴结转移(P0.05)。结论:CPT-TMC具有明显抑制卵巢癌细胞淋巴结转移效应,它可能成为一种新的有效的卵巢癌治疗药物。     

卵巢高/低级别浆液性癌的定量蛋白质组学比较研究

目的:探讨卵巢高级别浆液性癌和低级别浆液性癌的差异表达蛋白,为阐明卵巢癌发生机制及寻找诊断和预后标志物的提供线索。方法:收集卵巢癌新鲜组织标本冻存于液氮中,经病理学确诊为高级别浆液性癌和低级别浆液性癌,两种类型各收集15例。应用i TRAQ定量蛋白质组学技术筛选及鉴定高/低级别浆液性癌的差异表达蛋白,并进行生物信息学分析。结果:卵巢高级别和低级别浆液性癌组织的定量蛋白质组学比较研究鉴定出差异表达蛋白314个,其中与低级别浆液性癌组比较,高级别浆液性癌组上调蛋白有97种,下调蛋白有217种。GO分析显示这些差异蛋白在分子功能、生物学功能、细胞成分方面均具有一定分布特点。KEGG分析显示这些差异蛋白涉及复杂的信号通路。结论:高/低级别浆液性癌之间存在差异表达蛋白,这些蛋白涉及复杂的功能和信号通路可能在两型卵巢癌发生机制及肿瘤生物学行为差异中具有重要意义。     

Establishment of predictive model for analyzing clinical pregnancy outcome based on IVF-ET and ICSI assisted reproductive technology

ObjectiveIn order to explore the predictive model for analyzing clinical pregnancy outcomes based on IVF-ET (in vitro fertilization and embryo transfer) and ICSI (Intracytoplasmic sperm injection) assisted reproductive technology (ART). Methods: this study selected the embryo transfer (fresh) patients who received IVF-ET or ICSI treatment in the First Affiliated Hospital of Guangxi Medical University as the subjects. Moreover, the controlled ovarian stimulation (COS) and follow-up were conducted to collect relevant data for analysis, and finally a prediction model was established. Results: The results showed that the patients were divided into different ovarian response groups at first. The age, bFSH and bFSH/bLH were the highest in the poor ovarian response group (POR), followed by the normal ovarian response group (NOR) and the lowest in the high ovarian response group (HOR). The area under the ROC curve was 0.669 according to the predictive model of pregnancy-related factors. The confidence interval of 94% was 0.629–0.697, with statistical significance (P = 0.000, P < 0.01). Conclusion: it can be concluded that in clinical pregnancy, for many related factors, regression equation can be used to establish a prediction model to diagnose the success rate of pregnancy. In conclusion, a prediction model can be built based on the relevant experimental results, to provide experimental reference ideas for increasing the success rate of ART in late clinical pregnancy, which is of great research significance.     

Effect modification of body mass index on the association between ovarian cysts and endometrial cancer

BackgroundOvarian cysts represent a common condition among women. Epidemiologic studies are inconsistent in determining if women with cysts are more likely to develop endometrial cancer (EC) regardless of overweight/obesity. We investigated the combined role of cysts and body mass index (BMI) on EC risk.MethodsWe pooled data from three case-control studies conducted in Italy and Switzerland on 920 women with EC and 1700 controls. The prevalence of cysts was 5% among both cases and controls, with 63% of cases being overweight/obese. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using logistic regression models, adjusting for potential confounders. We conducted stratified analyses according to BMI, and estimated the interaction between cysts and BMI; we carried out additional analyses according to age at diagnosis of cysts.ResultsOverall, history of cysts was not associated to EC (OR=1.27, 95% CI=0.82–1.97, P = 0.29). Normal weight women reporting cysts had an increased risk of EC (OR=2.49, 95% CI=1.31–4.74), while no such effect was found among overweight/obese women (OR=0.65, 95% CI=0.36–1.18; P for interaction=0.004). The association was limited to women below 65 years of age and was stronger in those who reported cysts at age 48 or older.ConclusionsCysts appeared to be a risk factor for EC in lean women but not in overweight/obese ones; these results are consistent with an effect of cysts and obesity on EC along common pathways.     

The Photoperiodic Entrainment and Induction of Reproductive Rhythms in Male Blackheaded Buntings (Emberiza Melanocephala)

Groups of photosensitive, unstimulated or stimulated, male blackheaded buntings were subjected to photoregimes of 15 hr of green light of three intensities and 9 hr of dark per day. In some groups green light was interrupted with 90 min of bright fluorescent light at different times in the subjective day. While gonads did not develop or regressed in some groups, birds in others behaved as if exposed to long daylengths. The results besides suggesting the involvement of endogenous circadian rhythm during initiation and maintenance of gonadal growth indicate that the reproductive rhythms are entrained and induced by environmental photoperiod.