bluuebunny/crossref_metadata_2025 huggingface dataset:
Neuron-Specific Enolase and Embryology of the Trabecular Meshwork of the Rat Eye: An Immunohistochemical Study
Authors: Nucci P. , Tredici G. , Manitto M.P. , Pizzini G. , Rancato R.
Published: March 2018

Neuron-specific enolase (NSE) is a unique form of the glycolytic enzyme enolase found exclusively in neurons and neuroendocrine tissues.

Immunohistochemical techniques in which antineuron-specific enolase antibodies are used have made it possible to map out derivatives of the neural crest in humans. By using affinity-purified antibodies against NSE, we investigated whether the contribution of the neural crest cells to the development of the anterior ocular structures in the rat is similar to that in man. We found that filtration structures in rats show morphologically striking similarities with the analogous region of the human eye. Hence, the rat eye, with certain reservations, is a suitable model for experimental studies on ocular diseases that are characterized by chamber angle anomalies or congenital glaucoma.
DNA content in human colon cancer and non-neoplastic adjacent mucosa
Authors: Jotti G. Saccani , Fontanesi M. , Orsi N. , Sarli L. , Pietra N. , Peracchia A. , Sansebastiano G. , Becchi G.
Published: March 2018

DNA content was determined by flow cytometry in a series of 51 paired fresh tissue samples of primary colorectal carcinomas and the respective non-neoplastic adjacent mucosa in order to assess the relationship between DNA ploidy and the most commonly used prognostic factors. Aneuploidy was observed in 70.6% of the tumors and more than one aneuploid peak was present in 3.9%. Aneuploid tumor frequency was higher in left (93.3%) and right colon (64.7%) cancers than in rectal carcinomas (60.0%), and multiple aneuploid clones were detected more frequently in men than in women and in patients with advanced disease (Dukes stage D). Non-neoplastic mucosa adjacent to aneuploid tumors showed aneuploidy in 4 out of 51 samples (7.8%). The mucosa adjacent to diploid cancers had only diploid characteristics. Polidy did not correlate with histological abnormalities.

These findings suggest that DNA content as determined by flow cytometry needs further study with adequate follow-up to evaluate possible correlations with relapse-free and overall survival. Furthermore the aneuploidy of non-neoplastic mucosa provides evidence for a field defect in mucosa adjacent to colorectal cancer and supports the concept that this alteration may be of influence on carcinogenesis.
Study of serum tumor markers CEA, CA 15.3 and CA 27.29 as diagnostic parameters in patients with breast carcinoma
Authors: De Paterna L. Rodríguez , Arnaiz F. , Estenoz J. , Ortuño B. , Lanzós E.
Published: March 2018

Serum levels of CEA, CA 15.3 and CA 27.29 were measured during the follow-up of 499 breast cancer patients. Studies included three different groups of women: 82 blood donors free of disease, 42 patients with non-malignant breast diseases and 499 breast cancer patients. After the determinaion of cut-off values, serum levels of tumor markers did not show significant elevations in benign breast diseases. On the basis of our results CA 15.3 (sensitivity = 57%; accuracy = 87%) was the most effective marker, CA 27.29 (sensitivity = 62%; accuracy = 83%) was the most sensitive and CEA (sensitivity = 45%; accuracy = 81%) was the least sensitive and effective marker.

The combined use of markers was evaluated by step-wise logistic regression analysis. The regression coefficients showed that CA 15.3 (coeff. = 2.97) and CA 27.29 (coeff. = 1.46) were suitable for the detection of possible metastases during follow-up. Finally, we studied the relationship between pT, pN, pM and circulating levels of CA 15.3 and CA 27.29.
Longitudinal follow-up of breast cancer patients with the tumor markers CA 549 and CA 15.3
Authors: Vankrieken L. , Heureux F. , Longueville J. , De Hertogh R.
Published: March 2018

In order to verify the efficiency of the tumor markers CA 15.3 and CA 549 in the follow-up of breast cancer patients, it was necessary first to check the cutoff levels of each tumor marker in women with an increased age-related risk, but with no evidence of disease. From 132 serum samples in this age group, we confirmed the CA 549 cutoff level of 12.1 U/ml. However, the cutoff of CA 15.3 was 34 U/ml, which is higher than previously reported in the literature.

Fifty-two breast cancer patients with or without metastases at the time of entry into the study were followed for 2 to 3 years with both tumor markers. The sensitivity, specificity and the test efficiency for the presence of metastases were analyzed with each tumor marker. Taking into account the different cutoff levels, we concluded that both tumor markers can be used independently to follow the clinical situation of patients. In several cases an increase in both tumor markers was observed before a clinical diagnosis of metastases could be made. Combination of these two tumor markers gave no more significant information about the patient's clinical situation than each tumor marker alone.
Progesterone agonists and antagonists induce down– and up–regulation of estrogen receptors and estrogen inducible genes in human breast cancer cell lines
Authors: Savoldi G. , Ferrari F. , Ruggeri G. , Sobek L. , Albertini A. , Di Lorenzo D.
Published: March 2018

The effects of the synthetic progestin R5020 and the antiprogestin RU486 on the cellular content of estrogen receptors (ER) and on cell responsiveness to estrogens, have been investigated in the sex hormone-sensitive human breast cancer cell lines MCF-7 and T47D. When T47D cells were treated with R5020 (Promegestone) (10–8 M), ER was down-regulated to about 50% of the control level in a time-dependent manner. Maximum down-regulation was observed after 24 hours and remained at this level for the next 24 hours. Dihydrotestosterone (DHT) or dexamethasone (DEX) had no effect on ER sites. R5020 also down-regulated, although to a lesser extent, ER in the MCF-7 cells which contain fewer progesterone receptor (PR) sites.

When MCF-7 cells were transfected with a progesterone receptor expression vector (tMCF-7) to increase the number of PR sites, R5020 down-regulated the ER to a level similar to that reached in T47D cells. In both cell lines ER down-regulation was completely inhibited by a 10-fold molar excess of the antiprogestin RU486 (Mifepristone) (10–7 M). Surprisingly, when incubated with RU486 alone, T47D cells responded by up-regulating ER 2-4 fold.

The functional relevance of inhibition and up-regulation of ER for the estrogen responsiveness of hormone-sensitive human breast cancer cells was tested by assaying the synthesis of an estrogen-regulated product, the PS2 protein. Estrogen induction of this protein was inhibited by at least 70% in T47D cells exposed to R5020 for 24 hours before estrogen administration and by about 25% in MCF-7 cells under the same conditions. A 55% inhibition was observed in tMCF-7 cells. Up-regulation of ER by RU486 in T47D cells led to an increase in the estrogen induction of PS2 by about 18-20% compared to RU486 untreated cells.

These results indicate that the progestin and antiprogestin regulation of ER is functionally important for the estrogen responsiveness of breast cancer cells.
Analysis of antiglobulin (HAMA) response in a group of patients with B-lymphocytic malignancies treated with 131I-Lym-1
Authors: De Nardo G.L. , Kroger L.A. , Mirick G.R. , Lamborn K.R. , De Nardo S.J.
Published: March 2018

Host development of human anti-mouse antibodies (HAMA) in response to administered antibodies has been reported as a problem for antibody imaging and therapy. However, radioimmunotherapy has been shown to be effective in patients with B-cell malignancies because their immunodeficient state precludes or delays development of a HAMA response to mouse antibodies. Baseline HAMA activity was assayed in 60 patients with B-lymphocytic non-Hodgkin's lymphoma or chronic lymphocytic leukemia and sequentially in 43 patients who were subsequently treated with radiolabeled Lym-1 antibody. Pre-existing “HAMA” activity was found in 3 (5%) of the 60 patients screened for treatment consideration. The incidence of development of HAMA in the 43 patients treated with multiple doses of radiolabeled Lym-1 antibody was 12 (28%). There was no evidence for an anaphylactoid or related response in the HAMA positive patients. HAMA activity interrupted therapy in 14% of the patients (6 of 43) but did not preclude therapeutic responses to radiolabeled Lym-1 therapy. Median survival for the HAMA positive patients was longer (18 months) than for those who did not develop HAMA activity (9 months).
Evaluation of lipid-bound sialic acid (LSA) as a tumor marker
Authors: Sáez J.J. B. López , Senra-Varela A.
Published: March 2018

The objective of this study is the evaluation of serum levels of lipid-bound sialic acid (LSA) as a of marker cancer. This is a case-control study, and the levels of LSA were determined with blinded duplicates of cases and controls. Histologic verification of all cancer cases was used to confirm the diagnosis. The study included 135 patients with cancer (breast carcinoma, head and neck squamous cell carcinoma, lung cancer and gastrointestinal cancer) and 95 controls (57 normal subjects and 38 with chronic non-malignant diseases). Marker determination was done by the spectrophotometric procedure of Katopodis with resorcinol. The mean LSA level in the 57 healthy individuals was 15.09 mg/dl (95% C.I., 13.51-16.67), in the entire control group of 95 non-tumoral individuals it was 19.21 mg/dl (17.18-21.24), and in the 135 cancer patients it was 26.64 mg/dl (24.42-28.87). There was a statistically significant difference between patients with chronic non-tumoral diseases and healthy individuals (p<0.001) and also between cancer patients and healthy individuals (p<0.001), but not between cancer patients and patients with chronic non-tumoral diseases (p>0.05). The mean LSA serum values related to tumor site were (mg/dl): breast cancer, 21.49; gastrointestinal tumors, 28.45; head and neck cancer, 28.61 and lung cancer, 32.54. The means according to clinical stage were: complete remission, 18.50, significantly higher than the healthy controls (p<0.05); local disease, 23.50 (p<0.01); locoregional disease, (p<0.05); local disease, 23.50 (p < 0.01); locoregional disease, 27.21 (p < 0.001); metastatic disease, 34.49 (p < 0.001), and relapses, 20.87 (p<0.05). When comparing patients with clinically active cancer with healthy persons, the estimated cutoff value was 19.1 mg/dl, with a sensitivity of 74.7% and a specificity of 74.7%. We conclude that LSA values increase in cases of clinically active cancer and decrease in complete remission. LSA is of great value as a tumor marker in the diagnosis of disease extent.
Intraoperative Fall in Plasma Levels of Intact Parathyroid Hormone in Patients Undergoing Parathyroid Adenomectomy
Authors: Tommasi M. , Brocchi A. , Benucci A. , Manca G. , Borrelli D. , Cicchi P. , Cappelli G.
Published: March 2018

Intraoperative measurement of intact parathyroid hormone (PTH) can be used to evaluate the success of parathyroid surgery in primary hyperparathyroidism associated with parathyroid adenoma. To evaluate this approach we used a modified immunoradiometric assay (IRMA) to study the kinetic patterns of circulating PTH disappearance in 13 patients undergoing adenomectomy for single adenoma. The rapid and the standard assay for PTH measurement in plasma were used and compared. The two methods showed a highly significant correlation (r=0.995; p<0.0001).

We reported a decrease in PTH to 18.2±2.30 (mean±SEM) from baseline values at 15 minutes after successful parathyroid adenomectomy in the 13 patients. The biphasic pattern of serum PTH clearance was calculated in 8 of the studied patients with a fast phase showing a half-life (T1/2) of 3.99 (SEM 0.464) minutes and a slow phase with a T1/2 of 91.0 (SEM 33.6) minutes. Half the amount of the basal values was reached between 4 and 9 minutes.

Our study concludes that the modified IRMA for intraoperative measurement is feasible, reliable and sufficiently precise for low hormone values. Since it may yield information on the half-life of PTH in the circulation, it may play a role in the surgical guidance for total exeresis of hyperfunctioning tissue
Detection of Epstein-Barr virus Genome in Squamous Cell Carcinomas of the Larynx
Authors: Kiaris H. , Ergazaki M. , Segas J. , Spandidos D.A.
Published: March 2018

Epstein-Barr virus (EBV) is a B-lymphotropic virus with a tumorigenic potential. EBV infection has been recognized as the main cause of nasopharyngeal carcinoma and Burkitt's lymphoma. The aim of our study was to determine the incidence of EBV in squamous cell carcinomas of the larynx. We employed for our analysis a sensitive polymerase chain reaction (PCR) assay, followed by restriction fragment length polymorphism (RFLP) for further confirmation of the specificity of the PCR-amplification reaction. Our analysis revealed that 9 of 27 (33%) specimens harbored the EBV genome in the tumor tissue while only 4 (15%) specimens from adjacent normal tissue exhibited evidence of EBV infection. Three were EBV positive for both normal and tumor tissue. No association has been found with disease stage, histological differentiation and nodes at pathology. The relatively high incidence of EBV in the tumor tissue (33%) of patients with laryngeal cancer, as compared to the low (15%) incidence of the virus genome detected in the adjacent normal tissue of the patients, indicates a probable role of EBV in the development of the disease.
Growth Factors in Human Ovarian Follicle Fluid and Growth Factor Receptors in Granulosa-Luteal Cells
Authors: McWilliam R. , Leake R.E. , Coutts J.R.T.
Published: March 2018

The levels of oestradiol (E2), progesterone (P4), transforming growth factor a (TGFa), transforming growth factor β2 (TGFβ2), insulin-like growth factor I (IGF-I), platelet-derived growth factor AB (PDGF-AB) and epidermal growth factor (EGF) were measured in follicular fluids obtained from patients undergoing ovarian stimulation as part of an in vitro fertilisation program. Each of the substances was detected in all of the fluid samples tested, except TGFα (which was detected in 90% of samples tested), PDGF-AB (70%) and EGF (2%). Comparisons were made between each of these factors, follicular maturity, successful oocyte recovery and the outcome of fertilisation and embryo transfer. No statistically significant correlations were found. The presence of receptors for EGF, IGF-I and PDGF in extracts from granulosa-luteal cells isolated from follicular fluids was detected by means of Western blotting. The co-localisation of these growth factors and their receptors within the ovarian follicle suggests a likely role in control of follicular development.
Prostate-specific Antigen (PSA) and Cancer-Associated Serum Antigen (CASA) in Distinguishing Benign and Malignant Prostate Disease
Authors: Devine P.L. , Walsh M.D. , McGuckin M. A. , Quin R. J. , Hohn B. G. , Clague A. , Samaratunga H.
Published: March 2018

The Prostate-Specific Antigen (PSA) and the Cancer-Associated Serum Antigen (CASA) assay for the MUC1 mucin were compared in the serum of 303 patients with malignant or benign prostatic disease. Using cutpoints of 4, 10, and 20 μg/l, PSA was elevated in 93%, 81%, and 64% of patients with prostate cancer (n = 113), with corresponding specificities of 55%, 84%, and 96% in benign prostate disease (prostatic hyperplasia or prostatitis, n = 190). Using the recommended cutpoint of 4 Units/ml, CASA was elevated in 38% of patients with prostate cancer, with a specificity of 91% in benign disease. PSA and CASA showed a poor correlation in prostate cancer (r = 0.367) and benign disease (r = 0.158), and CASA was elevated in some PSA negative samples. Used together, PSA ≥20 μg/l and CASA ≥4 kU/l gave perfect specificity in benign disease, with a corresponding sensitivity of 29% (positive and negative predictive values of 100% and 70%, respectively). However, this combination gave no improvement over the use of PSA alone, with sensitivity 47% when the cutpoint was raised to give perfect specificity. These data suggest that CASA is of little use as an adjunct to PSA in the differentiation of benign and malignant prostate disease.
Reliability of volume or age-adjusted prostate specific antigen to improve diagnostic accuracy
Authors: Ciatto S. , Bonardi R. , Mazzotta A. , Santoni R.
Published: March 2018

Prostate Specific Antigen (PSA), PSA density, PSA excess, and PSA age-specific range have been compared in 331 subjects (35 cancers, 296 benign) with equivocal findings at screening by PSA or palpation + transrectal ultrasonography. The specificity of PSA using a cut-off of 4 ng/ml was only 0.49. A cutoff of 10 ng/ml improved the specificity to 0.88 but the sensitivity decreased from 0.97 to 0.63. The sensitivity and specificity for PSA density (cutoff 0.15), PSA excess (cutoff -5), and age-specific range were 0.86 and 0.80, 0.80 and 0.82, and 0.91 and 0.67, respectively. Avoided benign biopsies vs missed cancers on the basis of PSA density, PSA excess and PSA age-specific range would have been 19 and 5, 26 and 7, and 16 and 3, respectively. Methods adjusting for prostate volume allow a better interpretation of PSA values and may reduce the benign biopsy rate, but the consequent cost of delayed cancer diagnoses when the choice of biopsy is based only on these methods seems unacceptable.
Prostate Cancer Probability after Total PSA and Percent Free PSA Determination
Authors: Mione R. , Barioli P. , Barichello M. , Zattoni F. , Prayer-Galetti T. , Plebani M. , Aimo G , Terrone C. , Manferrari F. , Madeddu G , Caberlotto L. , Fandella A. , Pianon C. , Vianello L. , Gion M.
Published: March 2018

The percent free PSA value is a promising diagnostic tool for prostate cancer. However, its actual role has not yet been established because of the widely diverging sensitivity and specificity values. This could depend at least in part on analytical difficulties, since the free PSA concentration is much lower than that of total PSA. The present investigation was designed to evaluate the diagnostic performance of the percent free PSA in the most favorable analytical conditions.

Materials and methods

81 patients affected by newly diagnosed, untreated primary prostate cancer (CaP) and 239 patients with untreated benign prostatic hyperplasia (BPH) were prospectively enrolled. Hybritech total and free PSA were measured by the same technician using the same reagent batch.

Results

The percent free PSA was not significantly associated with age, tumor stage, gland volume, Gleason score, and total PSA, nor was it significantly affected by concomitant prostatic complications either in CaP or BPH. Percent free PSA was more effective than total PSA in the differential diagnosis between CaP and BPH in every evaluated dose range of total PSA. Percent free PSA determination could have reduced the rate of unnecessary biopsies in cases with total PSA ≥ 4 ng/mL and ≥ 10 ng/mL (avoided biopsies 61% and 63%, respectively). The post-test probability of the disease, which represents the proportion of patients with a positive percent free PSA value who have the disease, was, however, relatively low in younger patients with total PSA within the normal range.

Conclusions

The diagnostic performance of the percent free PSA value is enhanced when the methodological variability is reduced, particularly in men with low total PSA. Percent free PSA is superior to total PSA in distinguishing primary CaP from BPH in patients with total PSA between 2 and 30 ng/mL. The percent free PSA value is effective in reducing the rate of unnecessary biopsies in men with total PSA higher than 4 or 10 ng/mL. However, due to its relatively low post-test probability, the percent free PSA value should be interpreted with caution in the decision-making related to individual patients and should be used in association with clinical and instrumental evaluation of the patient.
Preliminary Evaluation of the Potential Prognostic Value of Serum Levels of Immunoglobulins (IgA, IgM, IgG, IgE) in Patients with Gastric Cancer
Authors: Tsavaris N. , Tsigalacis D. , Kosmas C. , Koufos CH. , Vaiopoulos G , Tzivras M. , Kouraklis G. , Papadimas V. , Georgoulis V. , Archimandritis A. , Sechas M.
Published: March 2018

Sixty patients with advanced gastric carcinoma who refused to receive cytotoxic chemotherapy were examined for serum immunoglobulin levels (IgG, IgM, IgA, IgE). Three samples were obtained every two months thereafter. The group of patients who had above-normal values of one or more of the examined immunoglobulins had a longer survival than the other (p<0.024). Immunoglobulin values were independent of the Helicobacter pylori antibody titer and of acute phase reactants. It is concluded that survival potentially correlates with serum immunoglobulin levels. Further studies including larger numbers of patients and correlating serum immunoglobulin levels with specific clinical parameters are needed to establish the prognostic role of serum immunoglobulins in patients with gastric carcinoma.
OVX1 and CEA in Patients with Colon Carcinoma, Colon Polyps and Benign Colon Disorders
Authors: Martell R.E. , Xu F.-J. , Davis W.Z. , Anselmino L. , Yu Y.H. , Daly L. , Bast R.C.
Published: March 2018

The OVX1 tumor marker promises to complement CA125 for detection of early stage ovarian carcinoma. OVX1 has also been shown to be elevated in colon cancer patients. This study is designed to assess serum OVX1 levels in patients with specific stages of colon cancer, colon polyps or other GI disorders. Serum OVX1 and CEA were measured by radioimmunoassay or enzyme immunoassay for 206 patients at the time of colonoscopy or staging for colon carcinoma. In patients with stage I, II, III, or IV colon carcinoma, serum OVX1 was positive in 37%, 48%, 74% and 63%, respectively. Fifty-three percent of patients with colon polyps had elevated OVX1 levels, while OVX1 levels were positive in only 7% of healthy controls. If both OVX1 and CEA were considered, at least one of these markers was elevated in 36%, 60%, 79% or 89% of patients with stage I, II, III or IV colon carcinoma, respectively. The majority of patients with inflammatory bowel disease or diverticulosis also had elevated OVX1 levels. Both markers were positive in 27% of patients with colon carcinoma, and not in any patients with a normal colonoscopy or with a diagnosis of diverticulosis or hemorrhoids. In conclusion, serum OVX1 improves the sensitivity of CEA for detecting colon polyps and colon cancer; however, the use of OVX1 in this setting is hindered by its elevation in non-malignant colonic processes.
Gonadotropin Levels in Ovarian Cyst Fluids: A Predictor of Malignancy?
Authors: Krämer S. , Leeker M. , Jäger W.
Published: March 2018

Gonadotropins can stimulate ovarian cancer growth in cell cultures. Corresponding LH/hCG receptors have been demonstrated in ovarian cancer. However, reduction of elevated serum gonadotropins by GnRH analogs in ovarian cancer patients did not lead to growth restriction, which means that serum levels of gonadotropins may not play the most important role in ovarian cancer. We therefore analyzed the LH and FSH concentrations in cyst fluids of ovarian cancer. Patients with preoperatively diagnosed cystic ovarian tumors were eligible for the study. Serum samples of the patients were obtained during surgery, while the fluids within the cysts were aspirated after surgical removal of the tumor. FSH and LH levels in serum and cyst fluids were measured using single antibody EIA (Boehringer Mannheim GmbH, Germany). Cyst fluids and sera of 108 patients were evaluated. While there were no significant differences in the FSH and LH serum concentrations, highly significant differences in the FSH and LH levels in cyst fluids were found. Only cancer cysts contained FSH and LH, while the corresponding concentrations in benign cysts were always below the measuring range of the assays. This clear division between high gonadotropin levels in cysts of serous ovarian cancer and low or absent concentrations in benign ovarian tumors further supports the hypothesis that FSH and LH may play a role in ovarian cancer; however, explanations for this surprising finding are still lacking.
More than 15 Years of CA 125: What is Known about the Antigen, Its Structure and Its Function
Authors: O'Brien T.J. , Tanimoto H. , Konishi I. , Gee M.
Published: March 2018

In 1997 CA 125 celebrated its 15th anniversary. Since the discovery of OC 125, an antibody that recognizes CA 125, by Bob Bast and his colleagues, considerable progress has been made toward the development of more sensitive and more precise assay systems. However, a great deal of mystery still remains about the CA 125 molecule and further enlightenment will probably not come until the gene for CA 125 is cloned and the complete open reading frame for the peptide core identified. In the meantime, we have learned some structural features of the CA 125 molecule as well as a little about its regulation and the requirements for its secretion or release from epithelial derived cells in cultures. The CA 125 molecule is almost certainly a glycoprotein with a predominance of O-linkages. It is heterogeneous with regard to both size and charge, most likely due to continuous deglycosylation of side chains during its life-span in bodily fluids. It exists as a very large complex (perhaps as much as 4 million daltons) under natural conditions. The core CA 125 subunit is in excess of 200,000 daltons and it retains the capacity to bind both OC 125 class antibodies and M 11 class antibodies. As a denatured purified subspecies the CA 125 molecule appears to autoproteolyse presumably due to an endogenous protease activity inherent to the molecule. Release or secretion of CA 125 appears directly linked to the epithelial growth factor receptor signal transduction pathway. Prior to its release from cultured cells, CA 125 is phosphorylated (at either/both serine and threonine) and dephosphorylated when released. To stimulate discussion on the regulation of CA 125 synthesis, its secretion and its structural configuration, we have presented a model of a theoretical CA 125 molecule. Perhaps it will provide a focus of attention until the CA 125 gene is cloned and the real molecule is described.
CA 125 - Epitopes and Molecular Size
Authors: Nustad K. , Onsrud M. , Jansson B. , Warren D.
Published: March 2018

CA 125 has two main immunogenic areas reactive with mouse and rat monoclonal antibodies. These areas are defined by the antibodies OC 125 and M11, respectively. Antibodies related to the main groups are named OC 125-like and M 11-like antibodies. The OC 125-like antibodies can be subgrouped into four sets, whereas the M 11-like antibodies segregate into many closely related binding specificities. One M 11-like antibody, ZR38, is not fully inhibited by any other M 11-like antibody and therefore represents a distinct subgroup. A single antibody, OV 197, is related to some OC 125-like antibodies, but not to OC 125. However, OC 125 enhances binding of OV 197 to its epitope. A new antibody, 7C 12, induces conformation changes, affecting binding of some M 11-like and some OC 125-like antibodies.

CA 125 exists as very large molecules that can be partly disrupted by SDS and heat. The form found in serum might be a degradation product from a larger molecule found in the abdominal and other serous cavities.
C-erbB-2 in Serum of Patients with Breast Cancer
Authors: Harris L. , Luftner D. , Jäger W. , Robertson J.F.R
Published: March 2018

c-erbB-2 is an oncoprotein which is overexpressed in some breast cancers. Recently it has been established that the extracellular domain of c-erbB-2 is shed into the serum of patients with breast cancer. There appears to be no association between tumor stage and extracellular domain of c-erbB-2 (c-erbB-2/ECD): c-erbB-2/ECD seems to correlate with patient prognosis whatever the stage of disease. The data also suggest that c-erbB-2/ECD may be useful in monitoring for tumor recurrence and in predicting resistance to hormonal therapy, but not as useful in predicting response to chemotherapy. This may relate to the power of this marker to reflect disease burden, which has an overwhelmingly negative impact on outcome.
Review of Clinical Studies of CA 27.29 in Breast Cancer Management
Authors: Beveridge R.A.
Published: March 2018

A critical review of CA 27.29 and CA 15-3 is performed in this paper. A review of the literature is undertaken. A review of the FDA submissions for 27.29 for both early stage and monitoring metastatic breast cancer patients is reviewed.
Multicenter Evaluation of the Performance and Clinical Utility in Longitudinal Monitoring of the Bayer Immuno 1™ Complexed PSA Assay
Authors: Allard W. J. , Cheli C. D. , Morris D. L. , Goldblatt J. , Pierre Y. , Kish L. , Chen Y. , Dai J. , Vessella R. L. , Chan D. W. , Schwartz M. K. , Zhou Z. , Yeung K. K.
Published: March 2018

We conducted a multicenter evaluation of the analytical and clinical performance of the automated Bayer Immuno 1™ complexed PSA (cPSA) assay, and compared assay performance to the Bayer Immuno 1™ PSA assay. We sought to determine whether measurements of cPSA could be of clinical utility in the management of patients with prostate cancer. Results of the 10–day imprecision across three evaluation sites produced total CV < 2.50% and an analytical sensitivity of 0.02μg/L. There was an increased trend in clinical sensitivity for prostate cancer with increasing stage of disease (71–86%). Clinical specificity for patients with benign urogenital disease was 74.8%, and for other nonprostate diseases ranged from 91.1–100%. Retrospective serial monitoring of 155 patients with prostate cancer demonstrated concordance of cPSA measurements to clinical status for 97% of the patients analyzed. Results from the clinical studies using the Bayer Immuno 1 cPSA assay were comparable to results obtained with the Bayer Immuno 1 PSA assay. The Bayer Immuno 1 cPSA assay demonstrates analytical performance and clinical effectiveness in the management of prostate cancer patients during the course of disease and therapy.
Disappearance Curves for Tumor Markers after Resection of Intrathoracic Malignancies
Authors: Yoshimasu T. , Maebeya S. , Suzuma T. , Bessho T. , Tanino H. , Arimoto J. , Sakurai T. , Naito Y.
Published: March 2018

Determination of the standard elimination kinetics of tumor markers will be helpful in the diagnosis of malignancies. We analyzed the disappearance curves for serum tumor marker levels after resection of intrathoracic malignancies. Serum levels of CEA, SLX, AFP, CA 19-9, SCC, TPA and CYFRA were measured several times after surgery in a total of 40 patients. To obtain precise biological half-lives, we applied non-linear least square analysis, taking into consideration the possibility of residual tumor cells. Disappearance curves were monophasic for CEA, SCC, TPA, CYFRA and SLX and biphasic for CA 19-9 and AFP. Temporary elevation of serum levels after surgery was observed for SCC, TPA and CYFRA. The average half-lives of CEA, SLX, SCC, TPA and CYFRA were 1.5 days, 2.7 days, 2.2 hours, 2.5 hours and 1.5 hours, respectively. The average half-life of CA 19-9 was 0.5 days in the first compartment and 4.3 days in the second compartment, while that of AFP was 1.0 days and 6.3 days, respectively. These values will be helpful in the interpretation of serum tumor marker levels after surgery.
CD30/CD30 Ligand and CD40/CD40 Ligand in Malignant Lymphoid Disorders
Authors: Younes A. , Carbone A.
Published: March 2018

CD30 and CD40 are members of the tumor necrosis factor (TNF) receptor family. These two receptors have pleiotropic biologic functions including induction of apoptosis and enhancing cell survival. This review will discuss the pattern of expression of these receptors in malignant lymphoid disorders and their prospective ligands. Understanding issues related to these two ligands and their receptors in lymphoid malignancies may help to improve the classification of these diseases and could open the doors for new treatment strategies.
Blood Concentrations of Tumor Necrosis Factor-Alpha in Malignant Lymphomas and Their Decrease as a Predictor of Disease Control in Response to Low-Dose Subcutaneous Immunotherapy with Interleukin-2
Authors: Lissoni P. , Bolis S. , MandalÀ M. , Viviani S. , Pogliani E. , Barni S.
Published: March 2018

Tumor necrosis factor-alpha (TNF-α), a cytokine provided by both immunomodulating and inflammatory activities, has been described to be abnormally increased in the blood of patients affected by malignant lymphomas, particularly NHL. However, the biological and clinical significance of TNF-α secretion in malignant lymphomas is still controversial. The present study was carried out to further define TNF-α secretion in untreated malignant lymphomas and during low-dose IL-2 immunotherapy. The study included 80 malignant lymphoma patients, 54 of whom were affected by HD and the other 26 by NHL. The mean TNF-α serum concentrations observed in untreated lymphoma patients were significantly higher than those seen in the healthy controls, without significant differences between HD and NHL. Moreover, both HD and NHL lymphoma patients at clinical stage III-IV showed significantly higher mean TNF-α levels than those at clinical stage I-II. Finally, patients with systemic symptoms had higher mean TNF-α concentrations than those without any systemic symptoms, even though statistical significance was observed only for NHL patients. In a second study we have evaluated changes in TNF-α levels in seven evaluable lymphoma patients (NHL: 6; HD: 1) - who did not respond to conventional therapies - during subcutaneous low-dose IL-2 (3 MIU/day 6 days/week for 4 weeks). Long-term stable disease was achieved in four patients with NHL, whereas the other three progressed. In patients with stable disease the mean TNF-α concentrations significantly decreased during treatment, whereas they increased in progressing patients. This study, by showing an abnormally enhanced TNF-α secretion in both NHL and HD patients with advanced disease and systemic symptoms and a decrease in its levels in patients who achieved disease control on IL-2 immunotherapy, appears to confirm the unfavorable prognostic significance of enhanced TNF-α levels in malignant lymphomas.
CA 72-4 Compared with Cea and CA 19-9 as a Marker of Some Gastrointestinal Malignancies
Authors: Lopez J.B. , Royan G.P , Lakhwani M.N. , Mahadaven M. , Timor J.
Published: March 2018

The objective of this study was to compare CA 72-4 with CEA and CA 19-9 in gastrointestinal malignancies. CA 72-4 was assayed by radioimmunoassay and CEA and CA 19-9 with the Abbott IMx analyser. The study included 52 patients with gastrointestinal cancer and 20 controls with benign gastrointestinal diseases. The 52 cases showed marker sensitivities of 39%, 49% and 35% for CA 72-4, CEA and CA 19-9, respectively, and 64% when the markers were combined. Marker expression in serum was highest in colorectal carcinoma followed by gastric and esophageal carcinoma. The sensitivities of the individual markers in colorectal, gastric and esophageal carcinomas, respectively, were: CA 72-4, 56%, 32% and 18%; CEA, 83%, 33% and 18%; CA 19-9, 53%, 25% and 18%. The sensitivity of the three markers in combination was 89%, 50% and 46% in colorectal, gastric and esophageal cancer, respectively. The specificity of CA72-4, CEA and CA 19-9 was 100%, 72% and 86%, respectively. However, CA 72-4 is not a useful a marker for gastrointestinal cancers because of its poor sensitivity. CEA, which had the best overall sensitivity and a reasonable specificity, was the most useful single marker, especially for colorectal cancer. Whereas the single markers were not useful in gastric and esophageal cancer, the combination of the three may be.
In Vitro Models of Angiogenesis: The use of Matrigel
Authors: Benelli R. , Albini A.
Published: March 2018

Tumor-induced angiogenesis is a key event for neoplastic progression. In vitro assays are important for identification of potential angiogenic agents and rapid sceening for pharmacological inhibitors. The increased interest in this field of study has generated several in vitro assays that recapitulate the steps of endothelial cell activation and differentiation. In this short report we emphasize the utility of Matrigel, a reconstituted basement membrane, to define two different steps in the angiogenic process: invasion in response to growth factors and organization of microvessels into a network with branching morphology on a Matrigel substrate.
The Role of the Thiol N-Acetylcysteine in the Prevention of Tumor Invasion and Angiogenesis
Authors: Morini M. , Cai T. , Aluigi M.G. , Noonan D.M. , Masiello L. , de Flora S. , D'Agostini F. , Albini A. , Fassina G.
Published: March 2018

We have extensively studied the effects of N-acetylcysteine (NAC), a cytoprotective drug that can prevent in vivo carcinogenesis. Here we review our findings NAC completely inhibits gelatinolytic activity of metalloproteases and chemotactic and invasive activities of tumor cells. In addition, NAC reduces the number of lung metastases when malignant murine melanoma cells are injected into nude mice. NAC treatment decreases the weight of primary tumors and produces a dose-related increase in tumor latency. Moreover, oral administration of NAC reduces the formation of spontaneous metastases. In experimental metastasis assays, we have found a synergistic reduction in the number of lung metastases after treatment with doxorubicin (DOX) and NAC in nude mice. In tumorigenicity and spontaneous metastasis assays, the combined administration of DOX and oral NAC again has shown synergistic effects on the frequency and weight of primary tumors and local recurrences and completely prevented the formation of lung metastases. The addition of NAC to endothelial cells strongly reduces their invasive activity in response to angiogenic stimuli. NAC inhibited the degradation and release of radiolabeled type IV collagen by activated endothelial cells, indicating that NAC blocks gelatinase activity. Oral administration of NAC reduces the angiogenic response induced by KS tumor cell products, confirming the ability of NAC to inhibit the invasive activity of endothelial cells in vivo and thereby blocking angiogenesis.
Clinical results of a new concept of neurothrombectomy coverage at a remote hospital—“drive the doctor”
Authors: Seker Fatih , Möhlenbruch Markus A , Nagel Simon , Ulfert Christian , Schönenberger Silvia , Pfaff Johannes , Ringleb Peter A , Steiner Thorsten , Bendszus Martin , Herweh Christian
Published: March 2018

Background

Many tertiary care hospitals cannot provide a continuous thrombectomy service due to the lack of a neurointerventionalist.

Aims

In this study, we present procedural and clinical results of a new concept in which neuroradiologists of a university hospital provide neurointerventional stroke service to a remote hospital (“drive the doctor”).

Methods

All consecutive patients with acute ischemic stroke due to large vessel occlusion of the anterior circulation treated with mechanical thrombectomy after hours at a remote hospital (distance of about 100 km) between 2012 and 2016 were analyzed retrospectively. These patients were compared to a group of patients referred to the above mentioned university hospital for MT over a comparable distance (“drip and ship”).

Results

A total of 60 patients were treated by “drive the doctor” and 66 patients were treated by “drip and ship.” Time from onset to imaging was similar in both groups (77 vs. 70 min, P = 0.6847). However, time from imaging to groin puncture was significantly lower in the “drive the doctor” model (112 vs. 232 min, P < 0.0001). Nonetheless, recanalization rate and clinical outcome were similar in both cohorts.

Conclusions

“Drive the doctor” is a feasible concept of neurothrombectomy coverage at remote hospitals. The presented data suggest that “drive the doctor” is not inferior compared to established stroke concepts such as “drip and ship” regarding recanalization rate and outcome. However, larger and prospective studies are necessary to confirm this finding.
Implementation of HbA1c Point of Care Testing in 3 German Medical Practices: Impact on Workflow and Physician, Staff, and Patient Satisfaction
Authors: Patzer Karl-Heinz , Ardjomand Payam , Göhring Katharina , Klempt Guido , Patzelt Andreas , Redzich Markus , Zebrowski Mathias , Emmerich Susanne , Schnell Oliver
Published: March 2018

Background:

Medical practices face challenges of time and cost pressures with scarce resources. Point-of-care testing (POCT) has the potential to accelerate processes compared to central laboratory testing and can increase satisfaction of physicians, staff members, and patients. The objective of this study was to evaluate the effects of introducing HbA1c POCT in practices specialized in diabetes.

Method:

Three German practices that manage 400, 550, and 950 diabetes patients per year participated in this evaluation. The workflow and required time before and after POCT implementation (device: Alere Afinion AS100 Analyzer) was evaluated in each practice. Physician (n = 5), staff (n = 9), and patient (n = 298) satisfaction was assessed with questionnaires and interviews.

Results:

After POCT implementation the number of required visits scheduled was reduced by 80% (88% vs 17.6%, P < .0001), the number of venous blood collections by 75% (91% vs 23%, P < .0001). Of patients, 82% (vs 13% prior to POCT implementation) were able to discuss their HbA1c values with treating physicians immediately during their first visit ( P < .0001). In two of the practices the POCT process resulted in significant time savings of approximately 20 and 22 working days per 1000 patients per year (95% CI 2-46; 95% CI 10-44). All physicians indicated that POCT HbA1c implementation improved the practice workflow and all experienced a relief of burden for the office and the patients. All staff members indicated that they found the POCT measurement easy to perform and experienced a relief of burden. The majority (61.3%) of patients found the capillary blood collection more pleasant and 83% saw an advantage in the immediate availability of HbA1c results.

Conclusions:

The implementation of HbA1c POCT leads to an improved practice workflow and increases satisfaction of physicians, staff members and patients.
The case of Sandra Nogueira and Others v Crewlink Ireland ltd and Miguel José Moreno Osacar v Ryanair Designated Activity Company. Comment to Court of Justice of the European Union (Second Chamber), judgement of 14 September 2017, Case C-168/16
Authors: Temming Felipe
Published: March 2018

One of the most fascinating branches of labour law – i.e. international labour law – is at the heart of a recent judgement of the ECJ. The case of Sandra Nogueira gives fruitful legal insights into Ryanair’s disadvantaging treatment of its employees and employees seconded as cabin crew with it. In this case note the author will first outline the ruling of the ECJ, and will then illustrate the impact of this important decision on legal practice.
Novel therapeutic strategies for degenerative disc disease: Review of cell biology and intervertebral disc cell therapy
Authors: Fernandez-Moure Joseph , Moore Caitlyn A , Kim Keemberly , Karim Azim , Smith Kevin , Barbosa Zonia , Van Eps Jeffrey , Rameshwar Pranela , Weiner Bradley
Published: March 2018

Intervertebral disc degeneration is a disease of the discs connecting adjoining vertebrae in which structural damage leads to loss of disc integrity. Degeneration of the disc can be a normal process of ageing, but can also be precipitated by other factors. Literature has made substantial progress in understanding the biological basis of intervertebral disc, which is reviewed here. Current medical and surgical management strategies have shortcomings that do not lend promise to be effective solutions in the coming years. With advances in understanding the cell biology and characteristics of the intervertebral disc at the molecular and cellular level that have been made, alternative strategies for addressing disc pathology can be discovered. A brief overview of the anatomic, cellular, and molecular structure of the intervertebral disc is provided as well as cellular and molecular pathophysiology surrounding intervertebral disc degeneration. Potential therapeutic strategies involving stem cell, protein, and genetic therapy for intervertebral disc degeneration are further discussed.
Chronic pelvic pain in benign and functional urological conditions: A review and comparison of the UK and European guidelines
Authors: Cashman Sophia , Biers Suzanne
Published: March 2018

We aim to provide a general overview of the available UK and European guidelines on non-oncological causes of chronic pelvic pain, and highlight any differences in practice. We have reviewed the current guidelines on chronic pelvic pain syndrome (defined as chronic pelvic pain with no identified underlying cause and/or the pain is non-specific or involves more than one organ) and other specific organ pain syndromes particularly relevant to urological clinical practice, including prostate pain syndrome, bladder pain syndrome and gynaecological causes of chronic pelvic pain. We have identified a relative paucity of UK guidelines, and accept that the European Association of Urology provides a comprehensive and current evidence based reference and guide which is utilised and regarded by most urologists as the ‘gold standard’ in UK practice.
EAU and NICE guidelines for the diagnosis and management of prostate cancer. How wide is the channel?
Authors: Jones Richard , Cornford Philip
Published: March 2018

Background:

Prostate cancer is the most common cancer in men in Europe. Both the European Association of Urologists (EAU) and the National Institute of Clinical Excellence (NICE) provide evidence-based guidelines for the diagnosis and management of prostate cancer. NICE is a national body involved in the production of efficacious guidelines for a wide spectrum of diseases across many specialities, whereas EAU is a specialist body of urologists and members of the urology multidisciplinary team across Europe. This paper describes the areas of agreement and explains the variations between these two often-quoted documents.

Objectives:

The objective of this paper is to review the guidelines of prostate cancer and to offer a comparison of prostate cancer guidance management for urologists and associated healthcare professionals.

Conclusion:

Both guidelines agree on areas of established consensus, especially in the diagnosis and staging of prostate cancer. There are however differences in the treatment algorithms, especially in advanced and metastatic disease. The differences in general seem to be due to the different functions and make-ups of the two bodies rather than disagreement on current evidence.
The management of non-muscle-invasive bladder cancer: A comparison of European and UK guidelines
Authors: Leiblich A , Bryant RJ , McCormick R , Crew J
Published: March 2018

Bladder cancer represents a significant health burden worldwide, with non-muscle-invasive tumours representing the majority of new bladder cancer diagnoses. Non-muscle-invasive bladder cancer (NMIBC) has a high prevalence and forms a large proportion of the caseload in urological practice, accounting for a significant cost in terms of urological healthcare. The last two decades have seen the development and refinement of guidelines from national and international organisations aiming to optimise management of NMIBC and bladder cancer in general. This review outlines the most recent European and United Kingdom guidelines on NMIBC, and in particular focuses on comparing and contrasting key recommendations from guidelines published by the European Association of Urology and the UK-based National Institute for Clinical Excellence.

Level of evidence: Not applicable for this multicentre audit.