The role of serum osteoprotegerine in metastatic prostate cancer - a case control study.

INTRODUCTION: Prostate cancer is one of the most common malignant neoplastic diseases in men. Early control of the disease progression contributes significantly to survival rates and patients' quality of life. Osteoprotegerin is a dimeric glycoprotein, which affects bone metabolism and inhibits osteoclastogenesis. In the present study, we evaluated the expression of osteoprotegerin in the serum of prostate cancer patients with or without skeletal metastases. METHODS: The expression of serum osteoprotegerin, as measured by enzyme-linked immunosorbent assay, has been studied in 82 patients with locally controlled prostate cancer, in 49 patients with metastatic bone disease and in a control group of 41 healthy males. At sampling time 65/131 of included patients were newly diagnosed, while 66/131 patients were already under hormonal therapy. All eligible prostate cancer patients had histologically confirmed malignancy. Serum total prostate-specific antigen (PSA) was determined by an immunoradiometric assay. We investigated the expression of osteoprotegerin in hormone-dependent and hormone-refractory prostate cancer and its relation to disease progression. RESULTS: Among the 131 patients with prostate cancer, higher osteoprotegerin and PSA concentrations have been observed in metastatic bone patients' sera (p <0.001). ROC analysis between the metastatic and locally controlled prostate cancer patients has shown a statistically significant area curve (p <0.001) and a cut-off limit of 89.6 pg/ml. Moreover, 15.3 % of patients became hormone-resistant, with osteoprotegerin values significantly increased compared with hormone-sensitive prostate cancer patients (p <0.001). CONCLUSIONS: It seems that elevated levels of serum osteoprotegerin in patients with prostate cancer reflect the bone metastatic extent and may potentially be used in metastatic patients' follow-ups. Hippokratia 2016, 20(2): 133-138.

Profiling serum HER-2/NEU in prostate cancer.

One of the four transmembrane receptors that belong to the erB family, is the HER2/neu oncoprotein. It forms heterodimers by binding to specific ligands, enhancing cell signaling and assisting in cell growth and differentiation. A variety of human epithelial tumors are characterised by an overexpression and gene amplification of the HER2/neu oncoprotein. This is the case of breast tumors, in which the receptor's overexpression and its gene have been studied extensively and its overexpression has been associated with unfavorable prognosis. In addition, HER2/neu plays a major role in understanding the oncogenesis of prostate adenocarcinoma. For this reason, clarifying the HER2/neu expression is particularly important in androgen independent prostate cancer (PCa), due to the increasing interest in using anti-HER2 targeted therapies for advanced disease treatment. On the other hand, the overexpression of HER2/neu has been reported to release soluble extracellular domain (ECD) in the serum of PCa patients. For this reason, the present review focuses only on studies referring to Serum HER2/neu levels in PCa patients. Serum levels of HER2/neu generally increase with advanced disease state and higher levels have been associated with recurrent or metastatic PCa and a clinically worse outcome. Therefore, it may be concluded that since there is a correlation between increased HER2/neu levels and a poor prognosis in prostate adenocarcinoma, serum HER2/neu could be used in clinical practice and follow up of patients with advanced PCa.

SPECT study with I-123-Ioflupane (DaTSCAN) in patients with essential tremor. Is there any correlation with Parkinson's disease?

OBJECTIVES: The differential diagnosis between essential tremor (ET) and Parkinson's disease (PD) may be, in some cases, very difficult on clinical grounds alone. In addition, it is accepted that a small percentage of ET patients presenting symptoms and signs of possible PD may progress finally to a typical pattern of parkinsonism. Ioflupane, N-u-fluoropropyl-2a-carbomethoxy-3a-(4-iodophenyl) nortropane, also called FP-CIT, labelled with (123)I (commercially known as DaTSCAN) has been proven to be useful in the differential diagnosis between PD and ET and to confirm dopaminergic degeneration in patients with parkinsonism. The aim of this study is to identify dopaminergic degeneration in patients with PD and distinguish them from others with ET using semi-quantitative SPECT (123)I-Ioflupane (DaTSCAN) data in comparison with normal volunteers (NV), in addition with the respective ones of patients referred as suffering from ET, as well as, of patients with a PD diagnosis at an initial stage with a unilateral presentation of motor signs. METHODS: Twenty-eight patients suffering from ET (10 males plus 18 females) and 28 NV (12 males and 16 females) were enroled in this study. In addition, 33 patients (11 males and 22 females) with an established diagnosis of PD with unilateral limb involvement (12 left hemi-body and 21 right hemi-body) were included for comparison with ET. We used DaTSCAN to obtain SPECT images and measure the radiopharmaceutical uptake in the striatum (S), as well as the caudate nucleus (CN) and putamen (P) in all individuals. RESULTS: Qualitative (Visual) interpretation of the SPECT data did not find any difference in the uptake of the radiopharmaceutical at the level of the S, CN and P between NV and ET patients. Reduced accumulation of the radiopharmaceutical uptake was found in the P of all PD patients. Semiquantitative analysis revealed significant differences between NV and ET patients in the striatum, reduced in the latter. There was also a significant reduction in the tracer accumulation in the left putamen of patients with right hemi-parkinsonism compared to ET and NV. Patients with left hemi-parkinsonism, demonstrated reduced radioligand uptake in the right putamen in comparison with ET and NV. Clinical follow-up of 20 patients with ET at (so many months afterwards) revealed no significant change in clinical presentation, particularly no signs of PD. Follow-up DaTSCAN performed in 10 of them (so many months afterwards) was negative in all but one. This one had an equivocal baseline study which deteriorated 12 months later. CONCLUSIONS: Our results do not support the hypothesis of a link between essential tremor and Parkinson's disease. However, it appears that ET patients have a small degree of striatal dopaminergic degeneration. If this is due to alterations in the nigrostriatl pathway or of other origin it is not clear. Follow-up studies of essential tremor patients are warranted to assess progression of disease and to understand better the possible cause for striatal dopaminergic degeneration.

Long acting somatostatin analogues in combination to antineoplastic agents in the treatment of small cell lung cancer patients.

BACKGROUND: Long acting somatostatin analogues combined with platinum analogues have demonstrated an antiproliferative effect on growth of human SCLC xenographs. METHOD: 130 previously untreated SCLC patients--54 with limited disease (LD) and positive somatostatin receptors were included in the study. All patients performed 111In-Octreotide scanning before chemotherapy (CHT), every 3 months and up to 4 times. All patients were treated with paclitaxel 190 mg/m2+carboplatin AUC=5.5 for up to 6 cycles. 47/130 patients (Group A, control group) received only CHT. Forty eight hours after each CHT 43/130 patients (Group B) were also administered 30 mg somatuline® (lanreotide) by a single subcutaneous (s.c.) injection to stimulate somatostatin receptors (SSTRS) for 2 weeks. 40/130 patients (Group C) received 60 mg somatuline® autogel to stimulate SSTRS for 4 weeks. Patients in Groups A and B after the completion of the CHT continued maintenance therapy with somatuline. NSE, IGF1, VEGFA, VEGFC, VEGFR2, HER2 levels were monitored. In histological samples Bcl-2 and VEGF were also explored by immunohistochemistry. RESULTS: No statistically significant differences were observed between the 3 Groups regarding LD and extensive disease (ED) patient ratios, age and PS. Group B had a survival benefit in comparison to Groups A and C (p=0.029). LD patients of Group B had a significant benefit compared to Groups A and C (p=0.012, Breslow test). In LD Group B had a significant longer TTP (p=0.02) in comparison to Groups A and C. Adverse effects had no statistically significant difference between the Groups and toxicity was well managed. INTERPRETATION: Long acting somatostatin analogues could be used as an additive therapy in combination to antineoplastic agents in patients positive for somatostatin receptors. A dose of 30 mg improved survival only in LD SCLC patients.

Radiation exposure to patients and radiologists during interventional procedures.

Patients who undergo interventional radiological examinations and the medical doctors who perform them receive a noticeable radiation dose. Twenty-six angiographies and six angioplasties were included in the present study. They were classified as examinations of lower limbs, abdominal aorta and aortic arch/carotid artery. Thermoluminescent dosemeters (TLDs) were placed underneath and over the lead apron of the doctors at all of the 32 examinations as well as next to the eyes and over the thyroid of 22 patients. Dose area product (DAP) values, time duration and other parameters were registered. Patients' effective dose (ED) and doses to the various organs were calculated with the aid of ODS-60 software. The EDs were normalised to DAP measured in each procedure. Based on TLD measurements, the Niklason method was applied for the calculation of doctors' ED. The calculated ED by ODS-60 were in the range of 0.00-1.46, 2.63-49.32 and 0.07-45.12 mSv for the three groups, respectively, while E/DAP indices were 0.023, 0.310 and 0.105 mSv Gy(-1) cm(-2). Very good correlation was found between TLD measurements of the eye and the thyroid of the patients and the relative values calculated by ODS-60. The ED for the radiologists ranged from 0.4 to 47.0 µSv for all the procedures. Taking into consideration the annual number of examinations performed in the department, the estimated dose to the radiologists' eyes is considerably high, so wearing leaded glasses is recommended for the optimisation of the procedure.

Radionuclide imaging with human polyclonal immunoglobulin (Tc-HIG) and bone scan in patients with rheumatoid arthritis and serum-negative polyarthritis.

BACKGROUND AND AIM: Rheumatoid arthritis (RA) is a chronic polyarthritic syndrome in which actively inflamed joints coexist with others being in remission. Compatible bone scan (BS) reveals joints with increased activity due to degenerative alterations, whilst scanning with human polyclonal immunoglobulin (HIG) is capable to show which of the joints present active inflammation of the synovial membrane. The aim of the study is to investigate the utility of molecular imaging with HIG in patients suffering from RA. PATIENTS AND METHODS: Forty patients (9 males plus 31 females), suffering from painful polyarthritic syndrome, with a mean age 45.3±7 years and a duration of disease 18.3±4.2 months were enrolled in the study. Twenty-six of the patients were serum positive to RA factor, considered as suffering from RA, whilst fourteen of them were RA factor negatives and they were considered as patients with serum-negative polyarthritis. All patients were submitted to x-rays and ultrasound examination (US) in joints of interest, plus whole body BS with (99m)Tc-MDP and finally scan with (99m)Tc-HIG. RESULTS: A total of 1680 joints have been evaluated. In 6 of the patients-two with serum negative RA (252 joints), radionuclide imaging with HIG was within normal limits, despite the fact that in compatible bone scan degenerative alterations have been mentioned in 30 joints. In all these patients disease was evaluated as inactive ("arthrotic changes"). In the remaining 34 patients-12 with serum negative RA (1428 joints), increased accumulation of HIG, concerning serum positive patients, has been mentioned to 163 joints ("arthritic changes"), whilst in the same group, BS revealed degenerative changes to 265 joints. Concerning serum negative patients, the respective results were 64 versus 190 joints. Increased uptake of HIG has been found in 189/226 swollen and painful joints (overall sensitivity according to clinical criteria 83.3%) and in 38 joints without any clinical evidence of inflammation, with clinical active inflammation presented after follow-up to 35 of them, yielding thus specificity at the level of 92%. Matched findings between these two methods have been mentioned to 185 out of 227 joints with an abnormal scan with HIG. Abnormal x-rays and US findings have been mentioned in 67 of the joints. CONCLUSIONS: According to the above mentioned, BS in RA reveals joints being actively inflamed or not, whilst radionuclide study with HIG is capable to distinguish actively inflamed joints, even in patients with serum negative RA, in a greater extent than anatomical imaging modalities.

A single measurement with (51)Cr-tagged red cells or (125)I-labeled human serum albumin in the prediction of fractional and whole blood volumes: an assessment of the limitations.

This study investigated variations in the prediction of blood volumes from a single measurement of red cell volume (RCV) with (51)Cr or plasma volume (PV) with (125)I human serum albumin (HSA). In 111 subjects, fractional and whole blood volumes were estimated from separate direct measurements of RCV and PV. The f ratio (body to venous hematocrit) was also determined. There was a very good correlation between (125)I-HSA measured PV (2857 +/- 822 ml) and that estimated with (51)Cr-tagged red blood cells (2864 +/- 747 ml) (r = 0.936, p = 0.000) and also between (51)Cr measured RCV (2600 +/- 774 ml) and that estimated with (125)I-HSA (2589 +/- 843 ml) (r = 0.944, p = 0.000). The 95% limits of agreement (mean +/- 2SD of differences, relative to the mean of paired data) ranged -0.2% +/- 20.3% and 0.4% +/- 21.4%, respectively. The 95% prediction intervals of measured from estimated fractional blood volumes spanned +/-20.3% and +/-19.5%, respectively, relative to the predicted values with regression equations. Proportional degrees of inaccuracy were found in whole blood volume estimations. The f ratio was inconstant and correlated with PV and the body hematocrit. We conclude that blood volumes can be determined reliabily only with direct measurements of RCV and PV. Estimated blood volumes may lead to misconceptions.

Impact of porcine Orexin A on glucagon plasma concentrations in pigs.

In 1998, Orexin A was added to the long list of orexigenic neuropeptides of the brain's physiology. Orexin A is involved in the central control of appetite and in energy homeostasis, as well as in the regulation of many other physiological functions. It is produced by a small cluster of the brain's neurons, located mainly in and around the lateral hypothalamic area. This site is known to be involved in regulating feeding in mammals. An intracerebroventricular injection of Orexin A into the rat's brain causes an impressive increase in the consumption of food, while an intravenous injection induces changes on glucagon plasma concentrations in rats. In addition, there are signs of changes on glucagon plasma concentrations when Orexin A acts on individual pancreatic islets of rats. In this study, we investigated the potential effects of the central administration of porcine Orexin A on glucagon plasma concentrations in pigs, and examined whether these changes are associated with the possible effect of the neuropeptide on the enteroinsular axis.

The effect of porcine Orexin A on insulin plasma concentrations in pigs.

Orexin A is a member of a wider family of orexigenic neuropeptides that have been recently discovered. They are produced by a small group of neurons located in the area of the brain, round the nucleus of the fornix (posterior hypothalamus), in the paraventricular nucleus, the dorsomedial nucleus, the ventromedial hypothalamus, as well as in the lateral hypothalamic region; these are sites that are known to be involved in regulating feeding in mammals. Orexin A is a neuropeptide, which is involved in appetite regulation and energy homeostasis. An intracerebroventricular (i.c.v.) injection of Orexin A in the brain of rats causes an impressive increase in food consumption. In addition, a subcutaneous or intravenous (IV) injection of Orexin A produces changes on insulin plasma concentrations in rats. Recent research suggests that Orexin A is also involved in regulating many other physiological functions. In this study, we examined the potential effects of the central administration of porcine Orexin A on insulin plasma concentrations in pigs, and whether these changes are connected with the possible effect of the neuropeptide on the enteroinsular axis.