The non-coding RNA interactome in joint health and disease.

Non-coding RNAs have distinct regulatory roles in the pathogenesis of joint diseases including osteoarthritis (OA) and rheumatoid arthritis (RA). As the amount of high-throughput profiling studies and mechanistic investigations of microRNAs, long non-coding RNAs and circular RNAs in joint tissues and biofluids has increased, data have emerged that suggest complex interactions among non-coding RNAs that are often overlooked as critical regulators of gene expression. Identifying these non-coding RNAs and their interactions is useful for understanding both joint health and disease. Non-coding RNAs regulate signalling pathways and biological processes that are important for normal joint development but, when dysregulated, can contribute to disease. The specific expression profiles of non-coding RNAs in various disease states support their roles as promising candidate biomarkers, mediators of pathogenic mechanisms and potential therapeutic targets. This Review synthesizes literature published in the past 2 years on the role of non-coding RNAs in OA and RA with a focus on inflammation, cell death, cell proliferation and extracellular matrix dysregulation. Research to date makes it apparent that 'non-coding' does not mean 'non-essential' and that non-coding RNAs are important parts of a complex interactome that underlies OA and RA.

MicroRNA-34a-5p Promotes Joint Destruction During Osteoarthritis.

OBJECTIVE: MicroRNA-34a-5p (miR-34a-5p) expression is elevated in the synovial fluid of patients with late-stage knee osteoarthritis (OA); however, its exact role and therapeutic potential in OA remain to be fully elucidated. This study was undertaken to examine the role of miR-34a-5p in OA pathogenesis. METHODS: Expression of miR-34a-5p was determined in joint tissues and human plasma (n = 71). Experiments using miR-34a-5p mimic or antisense oligonucleotide (ASO) treatment were performed in human OA chondrocytes, fibroblast-like synoviocytes (FLS) (n = 7-9), and mouse OA models, including destabilization of the medial meniscus (DMM; n = 22) and the accelerated, more severe model of mice fed a high-fat diet and subjected to DMM (n = 11). Wild-type (WT) mice (n = 9) and miR-34a-knockout (KO) mice (n = 11) were subjected to DMM. Results were expressed as the mean ± SEM and analyzed by t-test or analysis of variance, with appropriate post hoc tests. P values less than 0.05 were considered significant. RNA sequencing was performed on WT and KO mouse chondrocytes. RESULTS: Expression of miR-34a-5p was significantly increased in the plasma, cartilage, and synovium of patients with late-stage OA and in the cartilage and synovium of mice subjected to DMM. Plasma miR-34a-5p expression was significantly increased in obese patients with late-stage OA, and in the plasma and knee joints of mice fed a high-fat diet. In human OA chondrocytes and FLS, miR-34a-5p mimic increased key OA pathology markers, while miR-34a-5p ASO improved cellular gene expression. Intraarticular miR-34a-5p mimic injection induced an OA-like phenotype. Conversely, miR-34a-5p ASO injection imparted cartilage-protective effects in the DMM and high-fat diet/DMM models. The miR-34a-KO mice exhibited protection against DMM-induced cartilage damage. RNA sequencing of WT and KO chondrocytes revealed a putative miR-34a-5p signaling network. CONCLUSION: Our findings provide comprehensive evidence of the role and therapeutic potential of miR-34a-5p in OA.

High intensity interval training exercise as a novel protocol for cardiac rehabilitation program in ischemic Egyptian patients with mild left ventricular dysfunction.

BACKGROUND: Exercise-based Cardiac rehabilitation (CR) plays a major role in reducing mortality and morbidity in patients with coronary artery disease (CAD). The standard protocol is usually of moderate intensity exercise. High-intensity interval training (HIIT) consists of alternating periods of intensive aerobic exercise with periods of passive or active moderate/mild intensity recovery. AIM: This study aimed to assess HIIT program for ischemic patients attending CR after percutaneous coronary intervention (PCI) who have mild left ventricular dysfunction and to compare its effect on the functional capacity and quality of life with standard exercise CR program. PATIENTS AND METHODS: Our study included 40 patients with documented CAD, who participated in the outpatient CR program in Ain Shams University hospital (Al-Demerdash Hospital) divided into two equal groups, each included 20 patients. Group A included the patients who underwent standard cardiac rehabilitation program, while group B joined the high intensity interval training exercise protocol. RESULTS: Groups A and B showed significant improvement in all items of comparison; especially functional capacity, lipid profile and quality of life. Group B showed better improvements in the emotional well-being items of QOL parameters. CONCLUSION: We emphasize the positive effects of exercise-based CR program on patients with CAD and mild left ventricular dysfunction after PCI. The novel high intensity cardiac training proved to be safe and at least as beneficial as the standard moderate intensity cardiac training protocols, with better quality of life improvement.

Comparison between colloid preload and crystalloid co-load in cesarean section under spinal anesthesia: a randomized controlled trial.

BACKGROUND: Hypotension is a common problem during spinal anesthesia for cesarean delivery. Intravenous fluid loading is used to correct preoperative dehydration and reduce the incidence and severity of hypotension. Different fluid regimens have been studied but colloid preload and crystalloid co-load have not been compared. METHODS: In this randomized double-blind study, 210 patients scheduled for elective cesarean section under spinal anesthesia were randomly allocated to receive either 6% hydroxyethyl starch 130/0.4 500 mL before spinal anesthesia (colloid preload) or Ringer's acetate solution 1000 mL administered rapidly starting with intrathecal injection (crystalloid co-load). Maternal hypotension (systolic blood pressure <80% of baseline or <90 mmHg) and severe hypotension (systolic blood pressure <80 mmHg) were treated with 5 and 10mg ephedrine boluses, respectively. The primary outcome was the incidence of hypotension. Secondary outcomes included the incidence of severe hypotension, total ephedrine dose, nausea and vomiting and neonatal outcome assessed by Apgar scores and umbilical artery blood gas analysis. RESULTS: Data analysis was performed on 205 patients; 103 in the colloid preload group and 102 in the crystalloid co-load group. There were no significant differences in the incidence of hypotension (52.4% vs. 42.2%; P=0.18) or severe hypotension (15.5% vs. 9.8%; P=0.31) between colloid preload and crystalloid co-load groups, respectively. The median [range] ephedrine dose was 5 [0-45]mg in the colloid preload group and 0 [0-35]mg in the crystalloid co-load group (P=0.065). There were no significant differences in maternal nausea or vomiting or neonatal outcomes between groups. CONCLUSION: The use of 1000 mL crystalloid co-load has similar effect to 500 mL colloid preload in reducing the incidence of hypotension after spinal anesthesia for elective cesarean delivery. Neither technique can totally prevent hypotension and should be combined with vasopressor use.

Evaluation of the frequency and pattern of local recurrence following intersphincteric resection for ultra-low rectal cancer.

INTRODUCTION: Abdomino-perineal resection has been the standard treatment for rectal tumors located ≤5cm from the anal verge. Recently, intersphincteric resection became a valid option which preserves the bowel continuity with better functional outcome. AIM: Is to evaluate the oncological and functional outcome alongside the associated surgical morbidity in patients with T1-3 rectal cancer, who underwent intersphincteric resection (ISR). PATIENTS & METHODS: Between the years 2006 and 2011, 55 patients with invasive rectal adenocarcinoma, T1-3 lesions, located 2-5cm from the anal verge underwent ISR with total mesorectal excision. When inevitable, complete. ISR was performed, otherwise partial ISR was done. All T3 patients underwent total meso-rectal excision (TME) while some had lateral lymph node dissection (LND) with concomitant pelvic autonomic nerve preservation (PANP). RESULTS: Among the 55 patients, 21 (38.1%) patients were T1-2 and 34 (61.9%) patients were T3. The tumor location range was 0-5cm from the anal verge (median 2.3cm). Partial or complete ISR was done for 35 (63.6%) and 20 (36.4%), respectively. Patients were followed for a median of 1.5 years (range 1-4.6 years). The 3 year local recurrence and distant metastasis free rates were 85.2% and 85.6%, respectively. All the 3 local recurrences occurred in T3 patients group, and had positive circumferential resection margins. Overall 3-year disease-free survival was 82.6%; while the overall 3-year survival was 88.7%. CONCLUSION: Intersphincteric resection with TME does not affect the local recurrence or overall survival rate in early rectal cancer T1-2 & 3, with preservation of bowel continuity and better life quality.

Do women with pain and bleeding in early pregnancy require a vaginal speculum examination as part of their assessment?

AIMS: To investigate whether a vaginal speculum examination (VSE) prior to a transvaginal scan (TVS) alters the diagnosis or management of women who complain of bleeding in early pregnancy. METHODS: A prospective study. Women were asked to describe their bleeding as heavy, moderate or light and to consent to VSE prior to TVS. TVS was performed to obtain a final diagnosis of pregnancy outcome. RESULTS: 221 consecutive women were included in the study. In 14.5% (n = 32) complaining of heavy bleeding, blood was seen in all but two VSE and 84% (n = 27) had a miscarriage diagnosed by TVS. Products of conception were removed in 18.8% (n = 6), but this did not alter the subsequent immediate management of any cases. 65.2% (n = 144) of women complained of light bleeding, blood was seen on VSE in 53% (n = 77). Of these women, 25% (n = 19) of those where blood was seen had a miscarriage, compared to 6% (n = 4) of women where blood was not seen. A cervical ectropion was visualised in 11.7% (n = 26) and 2.3% (n = 5) had a cervical polyp. No other clinically significant pathology was detected. CONCLUSION: The amount of bleeding reported by women in early pregnancy relates well with VSE findings. Performing a VSE did not alter the subsequent management of these patients. This study demonstrates that routine objective assessment of blood by a clinician performing VSE prior to a TVS is unnecessary.

Mechanism of human chorionic gonadotrophin-mediated immunomodulation in pregnancy.

Human chorionic gonadotrophin (hCG) is released within hours of fertilization and has a profound ability to downregulate maternal cellular immunity against trophoblastic paternal antigens. It also promotes angiogenic activity of the extravillous trophoblast, and impairment of this function may lead to inadequate placentation and an increased risk of preeclampsia. There is increasing evidence that hCG alters the activity of dendritic cells via an upregulation of indoleamine 2,3-dioxygenase activity. This reduces T-cell activation and cytokine production, as well as encouraging Treg cell recruitment to the fetal-maternal interface. These changes are critical in promoting maternal tolerance. hCG is also able to increase the proliferation of uterine natural killer cells, while reducing the activity of cytotoxic peripheral blood natural killer cells. There are rare reports of autoantibodies directed against hCG or the luteinizing hormone/hCG receptor in women with recurrent miscarriage. These autoantibodies are more frequent in women with thyroid autoimmunity. This may explain the association between thyroid autoimmunity and impaired fertility. Downregulating these anti-hCG and anti-luteinizing hormone/hCG receptor autoantibodies may be helpful in some women with early miscarriage or recurrent failed in vitro fertilization.

Aberrant beta-catenin and LEF1 expression may predict the clinical outcome for patients with oropharyngeal cancer.

Beta-catenin, normally expressed on the epithelial cell surface, plays a crucial role in cadherin-mediated cell adhesion. Recent evidence suggests that beta-catenin is also involved in other functions such as intracellular signaling via the Wnt pathway by creating a nuclear complex with members of the Lymphoid-Enhancer-Factor/T-Cell-Factor (LEF/TCF) family of transcription factors, and gene regulation that it is implicated in the development of several tumors. Little information is available on beta-catenin expression and its main partner in the Wnt signaling pathway, LEF1, in oropharyngeal squamous cell carcinomas (OP-SCCs). The aim of this study is to investigate the expression of beta-catenin and LEF1 expression in human primary OP-SCCs and to evaluate their clinical and prognostic significance. OP-SCCs and normal peritumoral areas were analyzed by immunohistochemistry, Western-blot and RT-PCR. Beta-catenin was overexpressed in tumors in comparison to normal peritumoral areas and displayed predominantly intracellular (cytosolic/nuclear) localization in 62% of the tumors. Immunoreactivity was correlated with clinicopathological parameters and long-term follow-up, and a significant association was found between protein expression and development of local recurrences (P =0.03). The OP-SCCs with poor clinical outcome, which displayed intracellular beta-catenin expression, were also strongly positive for LEF1, with their co-expression statistically significant (P = 0.040). All (100%) advanced (stages 3+4) SCCs, 66.7% of the SCCs with positive lymph nodes and 80% of the SSCs that developed local recurrences were LEF1 positive. Cox regression analysis confirmed a poorer overall survival in cases with high expression of beta-catenin and LEF1. Our results suggest that assessing intracellular beta-catenin and LEF1 expression might help in patient risk stratification and outcome prediction, and serve as novel therapeutic targets in advanced OP-SCC.

Is serum human chorionic gonadotrophin follow-up necessary after suspected spillage of trophoblast at the time of laparoscopic surgery for ectopic pregnancy?

BACKGROUND: Persistent trophoblast is a recognised complication of salpingostomy for the treatment of ectopic pregnancy, with reported rates of 3-20%; hence, women are advised to have serum human chorionic gonadotrophin (hCG) levels monitored post-operatively. Although much less common, there are also reports of disseminated trophoblastic peritoneal implants after laparoscopic salpingectomy. The aim of this study was to assess whether monitoring of post-operative serum hCG levels is necessary in women undergoing salpingectomy, where intra-operative spillage of trophoblast is thought to have occurred. METHODS: This was a retrospective study of women who underwent serum hCG follow-up after salpingectomy. Serum hCG levels were monitored if: (1) the ectopic pregnancy was found to be ruptured; (2) there was a significant haemoperitoneum (>500 ml); (3) there was thought to be spillage of trophoblast at the time of salpingectomy or (4) a tubal miscarriage was diagnosed. Serum hCG levels were taken at days 1-2, days 3-4, days 6-8 or days 13-15 post-surgery. Women were followed up until the serum hCG level was <15 IU/l. Persistent trophoblast was defined as a failure of the serum hCG level to decrease spontaneously after surgery. RESULTS: 105 women underwent serum hCG follow-up after a laparoscopy for a tubal ectopic pregnancy. Of these women, 92 had a laparoscopic salpingectomy and 13 were diagnosed with a tubal miscarriage at the time of laparoscopy. In all women the serum hCG decreased spontaneously. CONCLUSION: It does not appear necessary to routinely monitor serum hCG levels post-operatively in women diagnosed with tubal miscarriages, in those undergoing salpingectomy for a ruptured ectopic pregnancy or in cases of salpingectomy, where there is thought to be spillage of trophoblast.

Bartholin's, vulval and perineal abscesses.

Perineal infections are a common presenting complaint in women attending acutely to a gynaecology department. Specifically, Bartholin's abscesses can occur in approximately 2% of women. Conservative versus surgical approaches to manage these infections aims to reduce the need for hospital admission. We summarise the literature on the diagnosis and management of Bartholin's and other types of perineal infections and abscesses specific to gynaecology.

NH4+-stimulated and -inhibited components of K+ transport in rice (Oryza sativa L.).

The disruption of K(+) transport and accumulation is symptomatic of NH(4)(+) toxicity in plants. In this study, the influence of K(+) supply (0.02-40 mM) and nitrogen source (10 mM NH(4)(+) or NO(3)(-)) on root plasma membrane K(+) fluxes and cytosolic K(+) pools, plant growth, and whole-plant K(+) distribution in the NH(4)(+)-tolerant plant species rice (Oryza sativa L.) was examined. Using the radiotracer (42)K(+), tissue mineral analysis, and growth data, it is shown that rice is affected by NH(4)(+) toxicity under high-affinity K(+) transport conditions. Substantial recovery of growth was seen as [K(+)](ext) was increased from 0.02 mM to 0.1 mM, and, at 1.5 mM, growth was superior on NH(4)(+). Growth recovery at these concentrations was accompanied by greater influx of K(+) into root cells, translocation of K(+) to the shoot, and tissue K(+). Elevating the K(+) supply also resulted in a significant reduction of NH(4)(+) influx, as measured by (13)N radiotracing. In the low-affinity K(+) transport range, NH(4)(+) stimulated K(+) influx relative to NO(3)(-) controls. It is concluded that rice, despite its well-known tolerance to NH(4)(+), nevertheless displays considerable growth suppression and disruption of K(+) homeostasis under this N regime at low [K(+)](ext), but displays efficient recovery from NH(4)(+) inhibition, and indeed a stimulation of K(+) acquisition, when [K(+)](ext) is increased in the presence of NH(4)(+).

H-7 and fetal calf serum (FCS) act synergistically to increase apoptosis in the KB line of human oral carcinoma cells.

There is a high incidence of oral squamous cell carcinoma (SCC) worldwide. The survival rate is among the lowest of the major cancers and has not improved significantly over the past two decades. The KB line of human oral carcinoma cells is a useful experimental system for studies of the biology of oral SCC. In a previous study, we reported inhibition of KB cell proliferation and stimulation of desmosome formation in confluent cultures treated with 20 microM H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine). In the present study, the effects of this protein kinase C (PKC) inhibitor on the survival of KB cells were investigated. Apoptotic cells were detected using a combination of Hoechst 33258 nuclear stain, TUNEL technique and ultrastructural analysis. Our results indicated that H-7 significantly increased apoptosis in KB cells in a dose-dependent manner. Maximal stimulation occurred at 100 microM, the highest dose of H-7 tested. Apoptotic cells exhibited nuclear fragmentation, chromatin condensation and apoptotic bodies. Interestingly, H-7 and fetal calf serum (FCS) acted synergistically to increase apoptosis in KB cells, suggesting that there is a serum activated subpopulation of H-7 target cells in the cultures. The underlying mechanism of activation remains to be elucidated. Our study suggests that the PKC inhibitor H-7 is a potentially useful cytostatic agent for oral carcinoma cells.

Down-regulation of desmosomal molecules in oral and pharyngeal squamous cell carcinomas as a marker for tumour growth and distant metastasis.

Down-regulation of adhesion molecules has been observed in a number of squamous cell carcinomas (SCC) and is considered to be associated with tumour invasiveness and lymph node metastasis. The present prospective investigation aimed at analyzing the expression patterns of desmosomal markers in oral and pharyngeal SCC and correlations that may exist between these patterns and tumour behaviour. Two constitutive desmosomal molecules, desmoplakin (Dp) and plakoglobin (Pg), were examined in 26 samples of primary carcinoma of the head and neck. The correlation between Dp and Pg expression was only moderate, reflecting functional differences between the two proteins. Whereas decreased Dp and Pg expression was closely associated with distant metastasis formation, reduced Pg expression was correlated to the development of large tumours. There were also variable relationships between the expression of these markers and lymph node invasion, histological differentiation, or survival of the patients. Biochemical analysis of cytoskeletal fractions confirmed the decrease in desmosomal proteins, particularly in tumours which later developed metastases. Down-regulation of Dp and Pg in oral and pharyngeal SCC may represent a reliable marker for extensive tumour growth and the risk of distant metastasis formation, Dp and Pg apparently having metastasis- and tumour-suppressor properties, respectively.

Involvement of desmoplakin phosphorylation in the regulation of desmosomes by protein kinase C, in HeLa cells.

In the present study, we have examined how modulation of protein kinase C (PKC) activity affected desmosome organization in HeLa cells. Immunofluorescence and electron microscopy showed that PKC activation upon short exposure to 12-O-tetradecanoylphorbol 13-acetate (TPA) resulted in a reduction of intercellular contacts, splitting of desmosomes and dislocation of desmosomal components from the cell periphery towards the cytoplasm. As determined by immunoblot analysis of Triton X-100-soluble and -insoluble pools of proteins, these morphological changes were not correlated with modifications in the extractability of both desmoglein and plakoglobin, but involved almost complete solubilization of the desmosomal plaque protein, desmoplakin. Immunoprecipitation experiments and immunoblotting with anti-phosphoserine, antiphosphothreonine and anti-phosphotyrosine antibodies revealed that desmoplakin was mainly phosphorylated on serine and tyrosine residues in both treated and untreated cells. While phosphotyrosine content was not affected by PKC activation, phosphorylation on serine residues was increased by about two-fold. This enhanced serine phosphorylation coincided with the increase in the protein solubility, suggesting that phosphorylation of desmoplakin may be a mechanism by which PKC mediates desmosome disassembly. Consistent with the loss of PKC activity, we also showed that down-modulation of the kinase (in response to prolonged TPA treatment) or its specific inhibition (by GF 109203X) had opposite effects and increased desmosome formation. Taken together, these results clearly demonstrate an important role for PKC in the regulation ofdesmosomal junctions in HeLa cells, and identify serine phosphorylation of desmoplakin as a crucial event in this pathway.

Cytokeratin alterations as diagnostic and prognostic markers of oral and pharyngeal carcinomas. A prospective study.

Cytokeratin (CK) alterations have been reported in carcinomas from different anatomical sites, and these have been associated with specific aspects of tumour behaviour. In order to assess the relationships between CK modifications and future tumour behaviour, we conducted the present prospective study on 26 squamous cell carcinomas (SCC) of oral and pharyngeal mucosae and corresponding controls. Cytokeratins were investigated using two-dimensional gel electrophoresis and immunofluorescence techniques. All healthy tissues, oral lining and oropharyngeal mucosae, expressed the oesophageal type CKs, including CK 19. Other simple epithelial CKs (7, 8, 17 and 18) were not detected. In carcinomas originating from corresponding sites, expression of oesophageal CKs varied widely from one specimen to another, and simple epithelial keratins were often found. Statistical analysis indicated correlations between CK expression and the clinicopathological data of SCC patients. Small tumour size was strongly associated with the expression of CKs 10 and 19. Interestingly, an absence of lymph node involvement was significantly associated with CK 18 expression. Tumours giving rise to recurrences, metachronous tumours, and distant metastasis were significantly associated with an absence of CK 13. These results suggest that CKs 10, 19, 18 and 13 could be reliable diagnostic and prognostic markers in the assessment of oral and pharyngeal squamous carcinomas.

H-7 stimulates desmosome formation and inhibits growth in KB oral carcinoma cells.

Protein kinase inhibitor H-7 was reported to stimulate desmosome formation in normal keratinocytes and to inhibit proliferation of neural cell lines. In the present study, the effects of this inhibitor on adhesion and growth of KB human oral carcinoma cells were investigated. H-7 was found to enhance desmosome assembly, as evidenced by an increased punctate labeling for the major desmosomal markers. Immunogold labeling confirmed the formation of desmosomes both at the cell surface and in the cytoplasm. In order to assess cell proliferation and possible correlation with adhesion, confluent cultures were treated and both adherert and detached cell fractions were counted. Under serum-free conditions, H-7 significantly reduced cell detachment. In contrast, EGF stimulated cell detachment, and this effect was abolished when cells were simultaneously treated with both EGF and H-7. Total cell counts were also significantly reduced by H-7, both in the presence and absence of EGF. Using the TUNEL technique, labeled cells were increased after H-7 treatment, thus implicating protein kinase inhibition in cell death. These results indicate that H-7 inhibits growth and stimulates adhesion of KB carcinoma cells.

Cytoplasmic desmosome formation by H-7 and EGF treatment in cultured fetal rat keratinocytes.

Cytoplasmic desmosomes (CD) are classically found in dyskeratotic cells of many epithelial tumors. Their significance and mechanism of formation remain largely speculative. Recently, we have reported the induction of these structures in rat keratinocytes following a brief treatment with acrylamide, and proposed that protein kinase inhibition may be implicated in their formation. In the present study, we show that protein kinase inhibitor H-7 in the presence of EGF is able to induce CD in rat keratinocytes within half an hour. In serum free medium containing 20 ng/ml of EGF, desmosomal structures at different stages of assembly were obtained using H-7 at concentrations ranging between 20 and 80 microM. No such structures were found at lower concentrations. The plaque diameters were significantly small in comparison with plasma membrane plaques. EGF induced plakoglobin positive membrane invaginations and in the presence of H-7, desmosomal plaques assembled on these membranes as either half desmosomes or as symmetric ones. The present results implicate protein kinase inhibition in CD formation and suggest that EGF provides tubular membrane structures in the cytoplasm on which desmosomes may assemble.

Soluble tumor necrosis factor receptors and CA 125 in serum as markers for epithelial ovarian cancer.

Increased serum levels of soluble tumor necrosis factor receptors (TNFRs) have been observed in patients with various types of malignancies. For the monitoring of ovarian cancer during treatment serum TNFRs have given information equivalent or better than that obtained by CA 125. In this study, we compared the diagnostic value of TNFRs and CA 125 in discriminating ovarian cancer from benign pelvic masses. Preoperative serum levels of p55 and p75, two distinct types of TNFRs, and that of CA 125 were determined by immunoassays in 45 patients with malignant and 27 patients with benign tumors operated consecutively. A group of 26 healthy women served as controls. For each of the three markers the group with ovarian cancer showed significantly higher values than the group with benign masses (p < 0.01). The rate of marker elevation correlated with ovarian cancer staging. Using upper cutoff levels of 2.0 ng/ml (p55), 4.3 ng/ml (p75) and 20 U/ml (CA 125), the calculated sensitivities were 58% (p55), 16% (p75) and 82% (CA 125). The specificities were 89% (p55), 96% (p75) and 85% (CA 125), respectively. Adding p55 to CA 125 did not increase the diagnostic values compared to using the CA 125 test alone. Our data confirm the superiority of serum CA 125 as a marker for discriminating ovarian cancer from benign pelvic masses. The p75 marker was found to be of no value, and for the detection of early stage ovarian cancer the sensitivity of p55 was too low to be of clinical importance.

Comparison between soluble tumor necrosis factor receptors and CA125 in peritoneal fluids as a marker for epithelial ovarian cancer.

The levels of the soluble forms of the membrane-bound receptor for tumor necrosis factor (TNF), p55 and p75, were assessed in peritoneal fluid samples from 50 patients with ovarian cancer, from 20 patients operated for benign pelvic masses, and from 26 healthy women undergoing laparoscopy. The 95% cutoff for normal levels were 14.0 and 5.2 ng/ml for p55 and p75, respectively. In patients with active ovarian cancer, elevated levels of p55 and p75 were found in 54 (p55) and 84% (p75) of the patients, and elevated levels were seen in all histologic types. The levels correlated with peritoneal fluid quantity and with stage of disease. Among 20 patients operated for benign pelvic masses, 1 patient had elevated p55 and 8 patients (40%) had elevated p75. The concentration of CA125 in peritoneal fluids showed a 95% cutoff value in healthy individuals of 8.950 U/ml; and elevated CA125 levels were found in 7 patients with ovarian cancer (14%) and in none of the patients with benign masses. The results indicate that in peritoneal fluid, measurement of soluble TNF receptors, and particularly of p75, has an increased sensitivity and accuracy over CA125 in distinguishing ovarian cancer from benign pelvic masses.