Melanoma inhibitory activity in Brazilian patients with cutaneous melanoma

Abstract BACKGROUND: Melanoma inhibitory activity is a protein secreted by melanoma cells and has been used as a tumor marker. Increased Melanoma inhibitory activity serum levels are related to metastatic disease or tumor recurrence. Currently there are no studies on Melanoma inhibitory activity and cutaneous melanoma involving Brazilian patients. OBJECTIVE: To evaluate the performance and feasibility of measuring Melanoma inhibitory activity levels in Brazilian patients with cutaneous melanoma. METHODS: Blood was obtained from ten patients with proved metastatic cutaneous melanoma (Group 1), 15 patients resected for cutaneous melanoma without metastasis (Group 2) and 5 healthy donors (Group 3). Melanoma inhibitory activity was measured using a commercially available ELISA kit. RESULTS: There was a statistically significant difference of Melanoma inhibitory activity levels between patients with and without metastasis (p=0.002), and between patients with metastasis and healthy donors (p=0.002). There was no difference between patients without metastasis and healthy donors (p=0.443). CONCLUSION: Melanoma inhibitory activity is a tumor marker for cutaneous melanoma and the Melanoma inhibitory activity-ELISA test can be easily performed. Patients with metastasis have increased Melanoma inhibitory activity serum levels when compared to patients without metastasis and healthy donors. .

Effect of Combined Sex Hormone Replacement on Bone/Cartilage Turnover in a Murine Model of Osteoarthritis

BACKGROUND: Estrogens act on estrogen receptors distributed in articular cartilages, synovial membrane, and ligaments, which are thought to be related with degenerative changes. Meanwhile, progesterone is known to have a weak anabolic action on bone formation This study evaluates the effects of estrogen and progesterone hormone on bone/cartilage turnover in ovariectomized (OVX) rats. METHODS: Thirty-five 7-month-old female Sprague-Dawley rats were randomly divided into 5 groups and then ovariectomized bilaterally except the sham control group. The first and the second group acting as controls did not receive hormonal therapy, the third group received estrogen, the fourth group received progesterone, and the fifth group received combination of both hormones 10 weeks after surgery. Evaluations were done using the serum levels of cartilage oligomeric matrix protein (COMP) for cartilage turnover, collagen type I C-telopeptide (CTX-1) and osteocalcin (OC) for bone turnover at 11, 15, 19 weeks after OVX and histology using the Osteoarthritis Research Society International (OARSI) osteoarthritis (OA) cartilage histopathology assessment system. RESULTS: Significantly less cartilage degradation (decreased levels of COMP) was found in the combined hormone treated group in comparison with OVX group. Similarly, both hormonal treatment resulted in increased bone formation and decreased bone resorption i.e., a low overall bone turnover status (decrease in the serum OC and CTX-1 levels). CONCLUSIONS: Combined estrogen and progesterone therapy was found to be convincing in terms of reducing the severity of OA in this experimental model.

Diagnostic and prognostic value of some biochemical markers in early knee osteoarthritis

Osteoarthritis [OA]; the most common joint disease, is not only characterized by cartilage destruction; but also by alteration of bone and synovial tissue metabolism, though their relative importance in the initiation and progression of OA is still debated. To identify patients with a high risk for destructive OA, more sensitive techniques than plain X-rays are needed. To study the diagnostic and prognostic value of some biochemical markers serum hyaluronic acid [HA] and serum cartilage oligomeric matrix protein [COMP], high sensitive C-reactive protein [hs-CRP] in the included patients had early OA knees and their relation to disease progression. Sixty patients had early knee OA and 20 control subjects were included. WOMAC index, laboratory investigations [COMP, HA, hs-CRP] and radiological evaluation [Kellgren and Lawrence grading scale and Thomas compartmental score] were performed for each patient at baseline and after one year. HA was significantly higher in patients than controls [p > 0.001] with the highest specificity and positive predictive value. It was significantly correlated with COMP at baseline and after one year [p = 0.01]. The levels of HA at baseline correlated with its levels after one year [p > 0.001]. It also correlated with K-L grading score [p = 0.02]. COMP was significantly higher in patients than controls [p > 0.001]. It was significantly correlated with Thomas score after one year [p = 0.007]. Baseline levels of COMP correlated significantly with its levels after one year [p = 0.005]. The differences of the serum levels of hs-CRP at the baseline evaluation and after one year between patients and controls were not statistically significant [p = 0.4, 0.5, respectively]. The measurements of HA and COMP may be of diagnostic and prognostic value in differentiating patients with early joint destruction and in determining disease progression. A single biochemical marker has definitive diagnostic value and the combination with other biochemical markers as well as with clinical and radiographic data would most likely help to improve the clinical assessment of patients. Serum hs-CRP is not a good predictor of individual patient progression and has a poor sensitivity and specificity

Serum COMP and their correlations with various disease parameters in patients with systemic lupus erythematosus and osteoarthritis

The cartilage oligomeric matrix protein [COMP] is a glycoprotein, which occurs mainly in an articular cartilage. The amount of this protein increases under the influence of cytokines and growth factors. As a result of various diseases that cause damage to cartilage, fragments of matrix protein are released into synovial fluid and then into blood. The assessment of matrix protein level in serum, for example COMP, permits the establishment of the degree of cartilage damage in inflammatory joint diseases, and permits observation of the effectiveness of the treatment. To assess serum COMP level, as a marker for cartilage degradation, in SLE and OA patients and to find a correlation between serum COMP level and other markers as well as activity of disease, disease duration and the age of the patients. Blood was collected from 40 systemic lupus erythematosus [SLE] patients group I, [the patients were further subdivided into two subgroups, group [Ia] comprised 20 SLE patients received 1 g IV methylprednisolone [MP] daily for three successive days, group [Ib] comprised 20 SLE patients did not receive IV methylprednisolone [MP]], and from 20 patients with knee osteoarthritis [OA] group II who constituted the control group. Serum COMP level was determined using an inhibition enzyme-linked immunosorbent assay [ELISA]. The measured values of the serum COMP level in SLE patients ranged from 1.32 to 1.71 microg/ml with a mean of 1.51 +/- 0.13 microg/ml in group [Ia], and ranged from 2.43 to 3.56 microg/ml with a mean of 2.86 +/- 0.31 microg/ml in group [Ib]. While in OA group [II] the value of serum COMP ranged from 0.97 to 2.65 microg/ml with a mean of 1.25 +/- 0.37 microg/ml. We found significantly elevated COMP levels in the SLE group [Ib] compared to the SLE group [Ia] patients and OA group [II] [p < 0.001]. We found a statistically significant positive correlations with the number of tender joints [correlation coefficient Pearson's: r = 0.45, p < 0.01], the number of swollen joints [r = 0.55, p < 0.001], SLAM value [r = 0.56, p < 0.001]. A significant positive correlation was found between serum COMP level and the ESR value in the first hour [r = 0.35, p < 0.001]. While the serum COMP level was independent of the patients' age [r = 0.04, p = NS], disease duration [r = -0.03, p = NS] and morning stiffness duration [r = -0.05, p = NS]. Also a Negative correlation was found between the serum COMP level and haemoglobin value [r = -0.11, p = NS]. As regards the OA group, no correlation was found between the serum COMP level and patients' age [r = -0.05, p = NS] and disease duration [r = 0.24, p = NS]. There were positive correlations between serum COMP and WOMAC index score for the lower limbs [r = 0.64, p < 0.05]. The serum COMP level can be an important marker of disease activity and cartilage destruction in SLE and OA Patients, and that serum levels of COMP can be used as a parameter for monitoring the therapy response in SLE patients undergoing an intravenous bolus steroid therapy

Serum levels of hyaluronic acid [HA] and cartilage oligomeric matrix protein [COMP] as predictors of disease progression in rheumatoid arthritis

To measure the serum concentrations of specific cartilage and bone molecules reflecting tissue turnover to investigate disease activity. The study included 30 rheumatoid arthritis [RA] patients with age range 42 - 66 years. Sixteen patients had rapid erosive disease and fourteen had slow erosive, compared with 20 matched apparently healthy volunteers. All studied individuals were subjected to full history taking, clinical examination and laboratory investigations including measurement of serum levels of cartilage oligomeric matrix protein [COMP], hyaluronic acid [HA], high sensitive C- reactive protein [CRP], erythrocyte sedimentation rate [ESR] and RF concentration as well as measurement of activity of RA by disease activity score [DAS] 28 joint counts. The study showed a significantly higher values of COMP, HA, CRP and ESR in slow erosive [p<0.001] and rapid erosive [p<0.0001] RA patients when compared to controls. There were significantly higher values of COMP, HA, CRP and ESR in rapid erosive RA patients compared to slow erosive RA patients. A significant positive correlation between serum levels of COMP and HA and age, disease duration, Larsen score, DAS and CRP and ESR was found. Also there was a significant positive correlation between serum levels of COMP and HA [r = 0.674, p<0.01]. It could be concluded that the measurement of some serological biomarkers that reflect bone and cartilage destruction in RA patients, could be used to investigate disease activity and increase the knowledge of the basic pathophysiology of joint disease

Evaluation of serum cartilage oligomeric matrix protein [Comp], soluble tumour necrosis factor receptor-II[sTNF-RII] and interleukin-6 [IL-6] levels in relation to serum estradiol, functional and radiologic findings in postmenopausal females with knee joint osteoarthritis

To evaluate the possible relation between serum levels of cartilage oligomeric matrix protein COMP, sTNF-RII, IL-6 and estradiol in post-menopausal females with clinically and radiologically documented osteoarthritic changes in the knee joint. Twenty post-menopausal females [PMOA] -with clinically and radiologically documented knee joint osteoarthritis were compared to a control group of ten post-menopausal females [control group [I]] and ten pre-menopausal females [control group [2]] "who were clinically and radiologically free of knee joint osteoarthritis. To all the studied subjects, a complete clinical examination was performed, including body mass index calculation, as well as scoring .systems for functional assessment of joint. Plain X-ray of both knee joints was performed. Serum samples were obtained for analysis of urea, creatinine, uric acid, total calcium, inorganic phosphates, C-reactive protein, rheumatoid factor COMP, sTNF-fUI, IL-6, and estradiol levels. The mean serum estradiol values in the PMOA, and control group [I] were significantly lower than their corresponding value in control group [2], and slightly lower in the PMOA than control group [1]. The mean serum COMP value was slightly higher in the PMOA group than its corresponding value in control group [1], and both mean sera values were significantly higher than their corresponding mean value in control group [2]. The mean serum sTNF-RII value was significantly higher in the PMOA group than its corresponding values in control group [1] and control group [2]. As regards mean serum IL-6 value, it was significantly higher in control group [1] than its corresponding values in the both PMOA and control group [2]. Based on ROC curve analysis in PMOA and control group [1], both serum COMP and sTNF-RII yitld a diagnostic specificity of 90% each, while the diagnostic sensitivity was 45% and 50% respectively. By using the combined approach, we were able to increase the diagnostic sensitivity of serum COMP and sTNF-RII to 90% and 83% respectively. On the other hand, the receiver operating characteristics [ROC] curve analysis of the same parameters in PMOA and control group [2], revealed a diagnostic sensitivity of 100% for each of serum COMP and s TNF-PJI as well as a diagnostic specificity of 90% for serum COMP and 70% for sTNF-RII. The fact that radiographic evidence of OA usually appears in advanced stages of the disease led to the need of identifying possible serum biochemical markers that could reflect the joint tissue status. From the above mentioned results, it could be concluded that the combined measurement of serum levels of the biochemical markers COMP and sTNF-RII may be used in identifying osteoarthritis in post-menopausal females. Furthermore, menopausal state per-se could play a role in the limitation of the diagnostic sensitivity of either of the two parameters if one of both analytes was chosen alone for measurement

Cartilage oligomeric matrix protein [COMP] in arthritis: is it a valuable serum marker of inflammation and bone mineral density changes?

Cartilage Oligomeric Matrix Protein [COMP] is a non-collagenous glycoprotein, which occurs mainly in an articular cartilage. This protein increases under the influence of cytokines and growth factors as a result of various diseases that cause damage to cartilage, fragments of it are released into synovial fluid and then into blood [serum COMP]. To assess the value of serum COMP [sCOMP] as an inflammatory marker in Rheumatoid Arthritis [RA], Systemic Lupus Erythematosus [SLE], Osteoarthritis [OA] patients, and to find its correlation with disease activity and bone mineral density changes [BMD]. This study was conducted on 100 subjects including ten healthy volunteers as group I, 30 RA patients [group II], 25 SLE patients [group III], and 35 patients with knee OA [group IV]. In addition to the physical examinations, activity was assessed in RA and SLE patients. WO MAC index was also performed for OA patients. Assessment of sCOMP level was determined, in addition to assessment of bone mineral density changes by DEXA, The mean values of sCOMP in RA, SLE and OA patients were 10.6 +/- 3.8 U/l 1L9 +/- 3.1U/1, and 10.9 +/- 2.9U/l respectively. In the control group it was 5.9 +/- L1U/L Serum COMP level in RA patients was significantly higher in patients with DAS >3.7 [p<0.05], and in patients with [ESR] value > 40 mm/h compared with patients with ESR value < 40mm/h [p<0.05]. A high significant elevation of sCOMP level was obtained in SLE patients with hemoglobin [Hb] <11.0 g/l, as well as those with ESR > 40 mm/h [p<0.01]. In addition, SLE patients with SLEDAI > 6 showed high significantly elevated sCOMP level than those with SLEDAI < 6 [p<0.01]. In OA patients, the level of sCOMP was significantly elevated in those with BMD < -2.5 than those with BMD >/= 2.5, High significant elevation was detected on comparing sCOMP level in either of group II, group III or group IV with group I [p<0, 01 for all]. In RA patients a significant positive correlation was detected between the sCOMP level and disease activity score [DAS], Hb, ESR [r = 0, 42, 0.39, 0.37 respectively] [p<0.05 for all]. In SLE patients a high significant negative correlation was found between the sCOMP level and Hb [r= -0.50, p<0.01], and significant positive correlation was found between the sCOMP level and ESR [r = 0.40, p<0.05]. In OA patients a significant positive correlation was found between the sCOMP level and WOMAC index [r =0.39], and high significant negative correlation between the sCOMP level and T-score [r=-0.60, p>0.01]. Measurement of sCOMP is valuable for monitoring inflammation in both inflammatory e.g. [SLE, RA] and degenerative joint diseases e.g. [OA] we observed its correlations with activity parameters in RA and SLE. More over OA patients had significant and high significant positive correlation of sCOMP with WOMAC index and the changes of bone mineral density [T-score] values respectively