bluuebunny/crossref_metadata_2025 huggingface dataset:
Touch Surgery: Analysis and Assessment of Validity of a Hand Surgery Simulation “App”
Authors: Tulipan Jacob , Miller Andrew , Park Andrew G. , Labrum Joseph T. , Ilyas Asif M.
Published: January 2018

Background: Surgical educators are increasingly exploring surgical simulation and other nonclinical teaching adjuncts in the education of trainees. The simulators range from purpose-built machines to inexpensive smartphone or tablet-based applications (apps). This study evaluates a free surgery module from one such app, Touch Surgery, in an effort to evaluate its validity and usefulness in training for hand surgery procedures across varied levels of surgical experience. Methods: Participants were divided into 3 cohorts: fellowship-trained hand surgeons, orthopedic surgery residents, and medical students. Participants were trained in the use of the Touch Surgery app. Each participant completed the Carpal Tunnel Release module 3 times, and participants’ score was recorded for each trial. Participants also completed a customized Likert survey regarding their opinions on the usefulness and accuracy of the app. Statistical analysis using a 2-tailed t test and analysis of variance was performed to evaluate for performance within and between cohorts. Results: All cohorts performed better on average with each subsequent simulation attempt. For all attempts, the experts outperformed the novice and intermediate participants, while the intermediate cohort outperformed the novice cohort. Novice users consistently gave the app better scores for usefulness as a training tool, and demonstrated more willingness to use the product. Conclusions: The study confirms app validity and usefulness by demonstrating that every cohort’s simulator performance improved with consecutive use, and participants with higher levels of training performed better. Also, user confidence in this app’s veracity and utility increased with lower levels of training experience.
The Abductive Art of Discovery
Authors: Caiata-Zufferey Maria
Published: January 2018

Qualitative analysis requires intuition, imagination, sensitivity, the creative linking of ideas, and a certain degree of luck. Interpreting and making sense of qualitative data have thus often been seen more as an art than a systematic activity. Because of its unstandardized character, the process of interpreting qualitative data has remained insufficiently described. This article looks retrospectively at the interpretation procedures that were used in a recent qualitative study, with the aim of identifying recurring mechanisms and basic conditions of discovery. The study was designed according to the grounded theory approach and dealt with the way unaffected women manage their genetic risk of breast and ovarian cancer. Specifically, this article offers various examples of the analytical reasoning that led to the transformation of observations into intelligible accounts. Based on these examples, the article concludes by identifying and illustrating five key moments in the process of knowledge construction: making a surprising observation, adopting a general principle of meaning, formulating hypotheses, verifying hypotheses, and constructing plausible explanations. These moments are not necessarily sequential but are instead intermingled in a typically abductive way. The complex process of discovery described may provide guidance to qualitative researchers in approaching their data and help them make their interpretative reasoning explicit, thus improving the transparency and credibility of qualitative reports.
Could be serum uric acid a risk factor for thrombosis and/or uveitis in Behcet’s disease?
Authors: Atıl Avcı , Deniz Avcı
Published: January 2018

Introduction

Serum uric acid level increases in many inflammatory conditions. Uric acid triggers the vascular inflammation and artery damage, which causes to an increased risk of endothelial dysfunction and atherosclerosis. It is not clear in the literature whether uric acid contributes to uveitis by similar mechanisms. We investigated whether uric acid level increases in Behcet’s disease patients with thrombosis or anterior uveitis.

Patients and methods

We reviewed the medical records of 914 Behcet’s disease. After screening for exclusion criteria, there were 50 Behcet’s disease patients with thrombotic complication and as the control group 202 BD patients without any vascular complication were included to the study. In the Anterior uveitis group, there were 53 Behcet’s disease patients. The Control group consisted of 39 Behçet’s disease patients without eye findings.

Results

Mean uric acid value was 4.96 ± 1.06 mg/dl in Behcet’s disease patients with thrombosis whereas 4.08 ± 0.94 mg/dl in controls, indicating a significant difference ( p < 0.001). There was no significant difference between the mean ages of the patients in both groups. The mean age of the BD group without eye findings was 39.31 ± 10.47 years and that of the Behcet’s disease with Anterior Uveitis group was 37.72 ± 9.65 years ( p = 0.453). The mean serum UA in the BD group without eye findings was 4.21 ± 1.21 mg/dl, while in the BD with Anterior Uveitis group it was 4.57 ± 1.37 mg/dl ( p = 0.201).

Conclusion

The extent of increase in uric acid level was greater in Behcet’s disease patients that have a thrombotic complication compared to those without thrombotic complication. Uric acid seems to play a role in the pathogenesis of thrombosis. It is concluded that the elevation of serum uric acid level in patients with anterior uveitis with Behcet’s disease is not statistically significant.
A Low-Density DNA Microarray for Analysis of Markers in Breast Cancer
Authors: Lacroix M. , Zammatteo N. , Remacle J. , Leclercq G.
Published: January 2018

Breast cancer remains a major cause of death in women from Western countries. In the near future, advances in both nucleic acids technology and tumor biology should be widely exploited to improve the diagnosis, prognosis, and outcome prediction of this disease. The DNA microarray, also called biochip, is a promising tool for performing massive, simultaneous, fast, and standardized analyses of multiple molecular markers in tumor samples. However, most currently available microarrays are expensive, which is mainly due to the amount (several thousands) of different DNA capture sequences that they carry. While these high-density microarrays are best suited for basic studies, their introduction into the clinical routine remains hypothetical. We describe here the principles of a low-density microarray, carrying only a few hundreds of capture sequences specific to markers whose importance in breast cancer is generally recognized or suggested by the current medical literature. We provide a list of about 250 of these markers. We also examine some potential difficulties (homologies between marker and/or variant sequences, size of sequences, etc.) associated with the production of such a low-cost microarray.
TP53 Mutations in Human Meningiomas
Authors: Verheijen F.M. , Sprong M. , Kloosterman J.M.E. , Blaauw G. , Thijssen J.H.H. , Blankenstein M.A.
Published: January 2018

Overexpression of p53 has been reported to play a role in the development of neoplasms of the central nervous system. Meningiomas are generally benign intracranial tumors originating from the meninges. Overexpression of the p53 protein in meningiomas and an association with histological type and recurrence has been reported. Mutation of the TP53 gene leads to a more stable p53 protein in quantities high enough for detection by immunohistochemistry. In the search for these mutations the core domain of the TP53 gene of meningiomas has been analyzed. Only a very low incidence of mutations was reported. The apparent discordance between overexpression of p53 protein and TP53 gene mutations may be explained by mutations located outside the core domain. This issue was addressed in the present study. All 11 exons of 17 meningiomas were analyzed for DNA alterations by PCR single-strand conformation polymorphism (PCR-SS-CP) analysis with subsequent sequencing. PCR-SSCP analysis showed a various number of band shifts and nucleotide alterations, caused either by alterations in the flanking introns or common polymorphisms (codon 36 and 72). The allele frequencies of the polymorphisms found in this small population of tumors resemble the frequencies reported in the literature. In addition, three nucleotide changes located in introns 2, 3 and 7 were found in 11, 3 and 4, respectively, of 17 specimens. Based on this study and on reports by others we conclude that it is not very likely that TP53 mutations are involved in the etiology of meningiomas.
Telomerase Activity in Breast Cancer in Western India (Gujarat)
Authors: Shah N.G. , Choksi T.J. , Patel D.D. , Vora H.H. , Ghosh N. , Trivedi T.I. , Trivedi K.A.
Published: January 2018

The purpose of this study was to examine the association of telomerase activity with clinical and histopathological prognostic variables in primary breast cancer (n=64). Telomerase activity in breast cancer was also compared with that in benign (n=10) and non-malignant tissues (n=8; post-lumpectomy tissues histopathologically defined as containing no residual tumor). The parameter was assessed using the Telomerase PCR ELISA kit. Values above OD 0.120 were considered positive. Estrogen and progesterone receptors (ER and PgR) were assayed by the dextran-coated charcoal method and levels >10 fmol/mg cytosol protein were taken as positive. Telomerase activity was detected in 20% and 50% of the patients with benign lesions and primary breast cancer, respectively, and in 50% of post-lumpectomy breast tissues histopathologically defined as containing no residual tumor. Telomerase activity was present in all stages of breast carcinoma and showed a significant inverse correlation with lymph node status (p=0.006), lymphatic invasion (p=0.035) and necrosis (p=0.033). Moreover, when stage II patients were grouped according to nodal involvement, a trend towards significance was observed (p=0.055). No correlation was observed with ER and PgR. The results of our study suggest that telomerase activity might be associated with the presence of cancer cells. Furthermore, telomerase activation may occur early in breast cancer and may be periodically downregulated during subsequent tumor progression.
Influence of 5-Fluorouracil and Folinic Acid on Interleukin-18 Production in Colorectal Cancer Patients
Authors: Merendino R.A. , Ruello A. , Cascinu S. , Ferlazzo B. , Bene A. , Bonanno D. , Quattrocchi P. , Caristi N. , Gangemi S.
Published: January 2018

Aims and Background

This study was carried out to evaluate the IL-18 blood concentrations of operated colorectal cancer patients and their possible variation in response to combination chemotherapy with 5-fluorouracil (5-FU) and folinic acid.

Methods

IL-18 levels were assayed in sera of 18 healthy donors and 18 surgical colorectal cancer patients before and after adjuvant chemotherapy with 5-fluorouracil and folinic acid. An ELISA kit for human IL-18 was used for the assay.

Results

Colorectal cancer patients showed significantly higher baseline levels of IL-18 than healthy donors (p<0.005). Furthermore, serum IL-18 levels increased significantly with respect to baseline in patients receiving adjuvant chemotherapy (p<0.005).

Conclusions

This study suggests that treatment with 5-fluorouracil and folinic acid may provoke an increase in IL-18 serum levels in colorectal cancer patients. This increase may help to explain the efficacy of adjuvant chemotherapy with 5-FU in colorectal cancer.
Reference Levels of the Tumor Markers Carcinoembryonic Antigen, the Carbohydrate Antigens 19-9 and 72-4, and Cytokeratin Fragment 19 Using the ®Elecsys Relecsys 1010 Analyzer in a Normal Population in Kuwait. The Importance of the Determination of Local Reference Levels
Authors: Behbehani A.I. , Mathew A. , Farghaly M. , van Dalen A.
Published: January 2018

The tumor markers CEA, CA 19-9, CA 72-4 and CYFRA 21-1 were analyzed in a group of apparently healthy subjects (n=232) in Kuwait using the ®Elecsys Relecsys 1010 analyzer. The distribution of the tumour marker levels was analyzed separately in Kuwaitis (n=103), non-Kuwaitis (n=129), smokers (n=68), non-smokers (n=164), males (n=138) and females (n=94). The distribution of CEA was significantly different in Kuwaitis vs. non-Kuwaitis in the total population (p=0.033) and in non-smokers (p=0.049); in males vs. females in the total population (p<0.0001) and in non-smokers (p=0.0002); and in smokers vs. non-smokers in the total population (p<0.0001) using the non-parametric Mann-Whitney U test. None of the other tumour markers showed significant differences in the subgroups. The upper reference level was defined as the 95th percentile of the normal values in each group. A higher reference level of CEA was observed in smokers (vs. non-smokers) in the total population. Also higher reference levels of CEA were observed in males (vs. females) both in the total population and in non-smokers. In the total population the respective reference levels were: CEA: 4.4 μg/L, CA 19-9: 35 kU/L, CA 72.4: 2.4 kU/L, and CYFRA 21.1: 2.1 μg/L. These results were compared with data in the kit inserts and literature data. The impact of 95th percentiles in a local heterogeneous population is discussed.
Insulin-Like Growth Factor II (IGF-II) Immunohistochemistry in Breast Cancer: Relationship with the Most Important Morphological and Biochemical Prognostic Parameters
Authors: Giani C. , Campani D. , Rasmussen A. , Fierabracci P. , Miccoli P. , Bevilacqua G. , Pinchera A. , Cullen K.J.
Published: January 2018

Recent in situ hybridization experiments have shown a high content of IGF-II mRNA in breast cancer stroma. The aim of this study was to examine the relationship between IGF-II protein expression and several prognostic parameters in 75 infiltrating ductal carcinomas (IDC) of the breast. Tissue sections were evaluated for proliferative activity, IGF-II protein, ER, PgR, p53, and p21 expression using immunohistochemical procedures. The degree of stromal proliferation was assessed. Menopausal status, axillary lymph node involvement and nuclear grade were known. Thirty-five patients (44.3%) were premenopausal and 47 (62.6%) had lymph node metastases. Marked stromal proliferation was found in 34 (45.3%) specimens and high nuclear grade in 20 (26.5%). Eighteen tumors (24%) showed no IGF-II immunostaining. In the positive cases, IGF-II was detected both in the tumor stroma and in the cytoplasm of epithelial cancer cells: a high IGF-II content was found in 12 specimens (16.0%), a low content in 14 (18.7%) and a moderate content in 31 (41.3%). Twenty-four tumors (32.0%) showed high proliferative activity. Both ER and PgR were expressed in the nucleus of cancer cells: 49 tumors (65.3%) were ER positive (ER+) and 34 (45.3%) PgR positive (PgR+). p21 protein was detected in 37 tumors (49.6%) and p53 in 12 (16%). IGF-II protein was not correlated with menopausal status, lymph node metastases, nuclear grade, proliferative activity, ER or p53. In contrast, IGF-II correlated strongly with stromal proliferation (p=0.008), PgR (p=0.03) and p21 (p=0.01). This study demonstrates that in IDC of the breast IGF-II protein is expressed in the epithelium and stroma of the majority of tumors and is correlated with stromal amount, PgR and p21 expression. These preliminary results indicate that IGF-II expression in breast cancer is connected with two important regulators of breast cancer growth and differentiation.
Vascular Endothelial Growth Factor Levels in Serum and Plasma following Esophageal Cancer Resection - Relationship to Platelet Count
Authors: Spence G.M. , Graham A.N.J. , Mulholland K. , Mcallister I. , Sloan J.M. , Armstrong M.A. , Campbell F.C. , Mcguigan J.A.
Published: January 2018

In patients with cancer circulating vascular endothelial growth factor (VEGF) may be tumor-derived and have prognostic significance. Activated platelets may also be a source of VEGF, releasing it in serum formation. Debate exists as to whether serum or plasma VEGF (S-VEGF, P-VEGF) is the most appropriate surrogate marker of tumor angiogenesis. As healing wounds produce VEGF that can spill over into the circulation, we aimed to investigate the potential confounding effects of cancer surgery on both perioperative S-VEGF and P-VEGF levels and to evaluate their relationship with platelet count. S-VEGF, P-VEGF and platelet counts were measured in 23 patients undergoing esophageal cancer resection. Samples were taken preoperatively and six weeks following surgery. Seven patients were also sampled on postoperative days 1, 5 and 10. VEGF was assayed using a commercial enzyme linked immunosorbent assay. S-VEGF and P-VEGF both rose after surgery (S-VEGF; day 5: 1017 [446–1224] pg/mL and day 10: 1231 [626–2046] pg/mL versus pre-op: 329 [189–599] pg/mL. P-VEGF; day 1: 55 [46–104] pg/mL and day 10: 58 [20–154] pg/mL versus pre-op: 23 [13–46] pg/mL), falling towards pre-operative levels by six weeks. Platelet count correlated with S-VEGF (rho=0.281; p<0.05, Spearman's rank) and P-VEGF (rho=0.330; p<0.01, Spearman's rank). Platelets may contribute to VEGF levels in plasma as well as in serum. The effects of surgery on S-VEGF or P-VEGF levels are mainly transient. Care must be exercised when interpreting circulating VEGF levels in the early postoperative period.
Prognostic value of Serum and Tumor Tissue CA 72-4 Content in Gastric Cancer
Authors: Aloe S. , D'alessandro R. , Spila A. , Ferroni P. , Basili S. , Palmirotta R. , Carlini M. , Graziano F. , Mancini R. , Mariotti S. , Cosimelli M. , Roselli M. , Guadagni F.
Published: January 2018

To date no general agreement has been reached regarding the prognostic significance of CEA, CA 19-9 and CA 72-4 as serum markers in gastric cancer, and only scattered information is available on the predictive value of marker expression in tumor tissue. Therefore, a longitudinal study was designed to analyze the presurgical serum and tumor tissue content of CA 72-4, CEA and CA 19-9 in 166 patients at different stages of gastric cancer, and to evaluate the possible correlation with clinicopathological features in respect to prognostic information on relapse-free survival. The results obtained showed that 48.4% of patients with tumor recurrence had positive presurgical CA 72-4 levels compared to approximately 24% of patients who remained free of disease. Furthermore, the median presurgical serum CA 72-4 levels were significantly elevated in relapsing patients. Serosa and lymph node involvement as well as positive presurgical serum CA 72-4 levels had independent prognostic value in predicting recurrence. A significant association between disease-free survival and lymph node involvement, depth of invasion and tumor tissue content of CA 72-4 was also demonstrated. We may therefore conclude that CA 72-4 antigen can be considered the marker of choice in the follow-up of gastric cancer patients and may be used as a prognostic indicator of relapse.
Antiangiogenic Activity of Chemopreventive Drugs
Authors: Pfeffer U. , Ferrari N. , Morini M. , Benelli R. , Noonan D.M. , Albini A.
Published: January 2018

Tumors growing within the host form dynamic aberrant tissue that consists of host components, including the stroma, an expanding vasculature and often chronic inflammation, in addition to the tumor cells themselves. These host components can contribute to, rather than limit, tumor expansion, whereas deprivation of vessel formation has the potential to confine tumors in small, clinically silent foci. Therapeutic inhibition of vessel formation could be best suited to preventive strategies aimed at the suppression of angiogenesis in primary tumors in subjects at risk, or of micrometastases after surgical removal of a primary tumor. Our analysis of potential cancer chemopreventive molecules including N-acetylcysteine, green tea flavonoids and 4-hydroxyphenyl-retinamide has identified antiangiogenic activities that could account -at least in part - for the tumor prevention effects observed with these compounds. These drugs appear to target common mechanisms of tumor angiogenesis that may permit identification of critical targets for antiangiogenic therapy and antiangiogenic chemoprevention.
Elevated 80K-H Protein in Breast Cancer: A Role for FGF-1 Stimulation of 80K-H
Authors: Forough R. , Lindner L. , Partridge C. , Jones B. , Guy G. , Clark G.
Published: January 2018

An increase in fibroblast growth factor-1 (FGF-1) is established as part of the cause of several important cancers including breast cancer, but the mechanisms by which it induces malignant behavior are not known. We now report that the protein 80K-H, a substrate for PKC, appears to be part of this mechanism and that it is increased in breast cancer and localizes to the nucleus as part of the mechanism. Our conclusion is based on an examination of a total of 58 biopsy specimens from human breast cancer patients for the presence of relationships between the 80K-H protein and the following: fibroblast growth factor receptor-1 (FGFR-1), tumor grade, microvessel counts (MVC), estrogen receptor (ER) and progesterone receptor (PgR) status. Based on histological grading and immunohistochemical (IHC) assays, we found strong direct relationships between 80K-H and FGFR-1 (r=0.49, p=0.003) and tumor grade (r=0.42, p=0.006). A trend for a direct relationship was observed with PgR (r=0.27, p=0.087). Notably, 80K-H immunostaining was largely limited to the epithelial cells of the mammary ducts.

Subsequently, we studied the effects of FGF-1 on 80K-H in cultured human mammary carcinoma epithelial cells in order to establish a more direct relationship between these two molecules. We observed that FGF-1 treatment of MCF-7 cells stimulated translocation of 80K-H protein to the cell nucleus, as demonstrated by subcellular fractionation studies. Maximal intranuclear 80K-H was observed approximately 30 minutes following FGF-1 treatment. In addition, FGF-1 treatment of MCF-7 cells increased growth and invasion of MCF-7 cells, as demonstrated by cell proliferation and a modified Boyden chamber assay, respectively. Further support for 80K-H nuclearization was provided by the immunostaining of human breast cancer specimens and computer-assisted identification of a putative nuclear localization signal (NLS) near the amino terminus of 80K-H protein structure.

These data support the existence of a previously unrecognized FGF-1/80K-H nuclear pathway in progression of human breast cancer and suggest that 80K-H may be useful for the assessment of breast tumor progression.
Prognostic and Predictive value of the Urokinase-Type Plasminogen Activator (uPA) and Its Inhibitors PAI-1 and PAI-2 in Operable Breast Cancer
Authors: Cufer T. , Borstnar S. , Vrhovec I.
Published: January 2018

The present study on the prognostic and predictive value of serine proteases was conducted in 460 early breast cancer patients mostly treated with some kind of adjuvant systemic therapy: 156 received chemotherapy, 141 hormone therapy and 111 a combination of both. Already in univariate analysis PAI-1 was the only proteolytic factor with a significant impact on DFS, which was retained in multivariate analysis (p=0.020); PAI-2 showed borderline significance in univariate analysis (p=0.0503) and uPA did not present as a significant prognostic factor for DFS in our patient series. In a separate univariate analysis of DFS on patient subgroups defined by adjuvant systemic therapy, a higher risk of relapse associated with higher uPA and PAI-1 levels was found in the subgroup of patients who did not receive any treatment; this difference did not reach the level of significance, probably due to the small number (n=52) of patients in this group (HR 1.37; p=0.71 and HR 2.14; p=0.321, respectively). A higher risk of relapse was also found in the subgroup of patients treated with adjuvant chemotherapy (HR 1.44; p=0.381 and HR 2.48; p=0.003, respectively). In contrast, the bad prognostic impact of high uPA and PAI-1 levels was lost in the subgroup of patients treated with adjuvant hormone therapy (HR 0.79; p=0.693 and HR 0.26; p=0.204, respectively). The same observations were made for the uPA/PAI-1 combination. Our study confirmed the prognostic value of serine proteases in early breast cancer. In addition, it pointed to a possible predictive value of these tumor markers for response to adjuvant hormone therapy with tamoxifen, which should be confirmed in further studies.
The Value of CEA and CA 19-9 in Detecting Cancer in a Group of High-Risk Subjects with Gastrointestinal Symptoms
Authors: Coban E. , Samur M. , Bozcuk H. , Ozdogan M.
Published: January 2018

The aim of this study was to evaluate the clinical value of CEA and CA 19-9 in a potential high-risk population of subjects with gastrointestinal complaints. The basic question was whether the determination of these markers, in addition to some other clinical features in this high risk population, could be helpful in diagnosing intraabdominal cancer. Two hundred and two patients with gastrointestinal complaints underwent standard diagnostic procedures and were followed for at least one year. For every patient, CEA and CA 19-9 levels were obtained at the first examination; the evaluating physician was blinded to the marker levels. The determinants of the likelihood of cancer were evaluated by multivariate analysis. Seventeen patients were diagnosed as having intraabdominal cancers. With the presence of melena (RR=101.63, p=0.007), nonspecific gastrointestinal symptoms (RR=12.54, p=0.026), increasing age (RR=1.09, p=0.028) and abnormal CEA (RR=240.79, p=0.000), the risk of having cancer increased significantly and independently. The presence of a primary gastric complaint was associated with a lower risk of cancer in this cohort (RR=0.01, p=0.04). Markers were not used in the diagnostic workup. In conclusion, in patients presenting with gastrointestinal complaints, the finding of elevated CEA levels may help in the diagnosis of cancer by prompting a more extensive search for intraabdominal cancer.
Limited Prognostic Value of c-erbB-2 Compared to uPA and PAI-1 in Primary Breast Carcinoma
Authors: Bouchet C. , Ferrero-Poüs M. , Hacène K. , Becette V. , Spyratos F.
Published: January 2018

In a retrospective study of 488 women with primary breast cancer, after a median follow-up of 10 years, we sought interactions between disease-free survival (DFS) and overall survival (OS) and tumor antigen levels of two components of the plasminogen system, urokinase-type plasminogen activator (uPA) and its inhibitor PAI-1, and the transmembrane growth factor receptor c-erbB-2. We used ELISAs (American Diagnostica, Greenwich, CT, USA) to quantify uPA and PAI-1 antigen levels in cytosols, and a double monoclonal antibody-based assay (EIA) (Ciba Corning Diagnostics, Alameda, CA, USA) to quantify c-erbB-2 in membrane extracts of the same tissues. Weak positive correlations were found between uPA and c-erbB-2 (rs=0.146; p=0.001) and between PAI-1 and c-erbB-2 (rs=0.154; p<0.001). In the overall population, using univariate analyses, c-erbB-2 overexpression and high uPA and PAI-1 antigen levels (>300 IU/mg, >1.40 ng/mg and >5.53 ng/mg, respectively) were significantly associated with shorter DFS (p=0.003, p<0.001 and p<0.001, respectively) and OS (p<0.001 in all cases). Using multivariate analyses, PAI-1, node status and tumor size were independent predictors of DFS and c-erbB-2 was retained in the model only for OS. In the node-negative subgroup, PAI-1 was the strongest significant survival predictor both for OS (p=0.003; HR 2.52) and DFS (p<0.001; HR 2.39). This study shows that in primary breast cancer c-erbB-2 offers no additional prognostic information when uPA and/or PAI-1 are candidates in the multivariate analyses.
TP53 Codon 72 Polymorphism does not Affect Risk of Cervical Cancer in Patients from the Gambia
Authors: Tanara G. , Falugi C. , Cesario A. , Margaritora S. , Russo P. , Cosimi A.
Published: January 2018

Aims

A case-control study was performed to investigate the relationship between cervical cancer and TP53 polymorphism at codon 72 in young black African women from The Gambia.

Materials and Methods

The TP53 polymorphism at codon 72 was examined by PCR amplification and SSCP analysis in 40 patients with primary cervical cancer and in 20 healthy women of the same age and from the same geographical area. The occurrence of TP53 polymorphism in combination with the HPV-16 E6 genotype (assayed by PCR) was evaluated.

Results

The distribution of TP53 genotypes in cervical cancer patients and in the control group was not statistically different (p=0.45) and homozygosity for argine at residue 72 was not associated with cervical cancer (odds ratio: 1.24; 95% confidence interval 0.21-9.16). Similarly, a different genotype distribution, cervical cancer and presence of HPV-16 E6 were not observed.

Conclusions

These results cannot rule out an association between TP53 polymorphism at codon 72, HPV infection and the etiology of cervical cancer in this population sample.
Analysis of Bone Alkaline Phosphatase as a Marker for the Diagnosis of Osteoporosis in Men under Androgen Ablation
Authors: Morote J. , Trilla E. , Esquena S. , Abascal J.M. , Segura R.M. , Catalan R. , Encabo G. , Reventós J.
Published: January 2018

The objective of this study was to evaluate the usefulness of serum determination of bone alkaline phosphatase (BAP) in the diagnosis of osteoporosis in men with prostate cancer under androgen ablation. Serum levels of BAP and bone mineral density (BMD) were assessed in 110 patients with non-metastatic, treated prostate cancer. Fifty-eight patients were under androgen deprivation during a period between two and 96 months and 52 had been submitted only to radical prostatectomy. Mean serum BAP was 11.8 ng/mL in patients with normal BMD, 16.7 ng/mL in patients with osteopenia (p. 0.058), and 19.3 ng/mL in patients with osteoporosis (p=0.044). The correlation between serum BAP and BMD was significant (p. 0.006) but with an index of only 0.26. Receiver operating characteristic analysis for the diagnosis of osteoporosis showed an area under the curve of 0.608. None of the cutoff points that provided specificities of 75%, 90% and 95% gave significant distributions. The positive and negative predictive values as well as the odds ratios were not of any clinical usefulness. We conclude that serum BAP should not be considered a good marker for the diagnosis of osteoporosis in men with prostate cancer. Therefore, BAP serum determination cannot replace bone densitometry as a diagnostic tool.
On the Clinical Usefulness of the Free-to-Total Prostate-Specific Antigen Ratio
Authors: Ciatto S. , Rubeca T. , Franceschini R. , Trevisiol C. , Confortini M. , Pontenani G. , Lombardi C.
Published: January 2018

The free-to-total prostate-specific antigen ratio (F/T PSA) is associated with the presence of prostate cancer and is thus used as an indicator for suspicion of prostate cancer and as a determinant for biopsy. We reviewed a recent retrospective series of 966 consecutive prostate biopsies where F/T PSA was blindly determined and did not influence biopsy indication. We simulated the association of F/T PSA with biopsy outcome and its impact as a biopsy determinant. When adopting an F/T PSA cutoff of 10%, 13%, 16% or 20% among random sextant biopsies in the 4–10 ng/mL total PSA range, the sensitivity was 15%, 37%, 55% and 72% and the specificity 89%, 80%, 64% and 44%, respectively. Using F/T PSA as a biopsy determinant, from 1.7 to 2.6 cancer biopsies would have been delayed to avoid 10 benign biopsies. As this balance is not acceptable, F/T PSA has no role as a biopsy indicator and its clinical use is questionable.
Levels of Tissue Inhibitor of Metalloproteinases 1 in Plasma and Urine from Patients with Bladder Cancer
Authors: Holten-Andersen M.N. , Brünner N. , Nielsen H.J. , Christensen I.J. , Møller Sørensen N. , Schrohl Rasmussen A.-S. , Primdahl H. , Ørntoft T.
Published: January 2018

Aim

To assess the potential use of plasma and urine levels of tissue inhibitor of metalloproteinases 1 (TIMP-1) in urothelial cancer.

Methods

TIMP-1 levels were determined in urine and plasma from healthy donors (n=26), patients with bacterial bladder infection (n=24), urothelial bladder adenoma (n=3) or adenocarcinoma (n=7).

Results

Free and total TIMP-1 in plasma were weakly but significantly correlated with age; urinary TIMP-1 was not. A strong correlation between free and total TIMP-1 in plasma was observed, with an average ratio of 0.85. No correlation between total TIMP-1 in urine and plasma was found (p=0.55). No significant differences in free or total TIMP-1 in plasma were found between healthy individuals, patients with cystitis or bladder cancer (p=0.4). Urinary TIMP-1 levels were significantly increased in patients with cystitis (p=0.001). No apparent differences in TIMP-1 levels were found in patients with bladder cancer at different stages.

Conclusion

Our previous observation of a weak but significant correlation between plasma TIMP-1 and age was confirmed. Likewise, an association between free and total TIMP-1 in plasma with a ratio of 0.85 was established. No correlation between plasma and urine TIMP-1 was found. Measurement of TIMP-1 in plasma and/or urine is apparently not useful for the identification of bladder cancer.
Association of TP53 Mutation, p53 Overexpression, and p53 Codon 72 Polymorphism with Susceptibility to Apoptosis in Adult Patients with Diffuse Astrocytomas
Authors: Uno M. , Oba-Shinjo S.M. , Wakamatsu A. , Huang N. , Alves V. Avancini Ferreira , Rosemberg S. , de Aguiar P.H. Pires , Leite C. , Miura F. , Junior R. Marino , Scaff M. , Nagahashi-Marie S.K.
Published: January 2018

Clarification of TP53 alterations is important to understand the mechanisms underlying the development of diffuse astrocytomas. It has been suggested that the alleles of TP53 at codon 72 differ in their ability to induce apoptosis in human cancers. The aim of this study was to analyze the possible association of TP53 mutation, p53 overexpression, and p53 codon 72 polymorphism with susceptibility to apoptosis in adult Brazilian patients with diffuse astrocytomas. We analyzed 56 surgical specimens of diffuse astrocytomas for alterations of TP53, using polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) direct sequencing. p53 and cleaved caspase 3 protein expression were assessed by immunohistochemistry. We found TP53 mutations in 19.6% (11 out of 56) of tumors tested, with the lowest mutation rate found in the cases of glioblastomas (8.8%) (p = 0.03). Only 16.1% of tumors tested showed cleaved caspase 3-positive staining, demonstrating that apoptosis is very inhibited in these tumors. All tumors having TP53 mutation and p53 accumulation had no expression of cleaved caspase 3. Additionally, no association was observed in tumors having proline and arginine alleles and expression of cleaved caspase 3. We concluded that clarification of the TP53 alterations allows a better understanding of the mechanisms involved in the progression of diffuse astrocytomas, and the allele status at codon 72 was not associated with apoptosis in these tumors.
p53 and HER2/neu Expression in Relation to Chemotherapy Response in Patients with Non-Small Cell Lung Cancer
Authors: Fijołek J. , Wiatr E. , Rowińska-Zakrzewska E. , Giedronowicz D. , Langfort R. , Chabowski M. , Orłowski T. , Roszkowski K.
Published: January 2018

The aim of the study was to investigate a relation between p53 and HER2/neu expression in resected lung tumors and the response of those tumors to neoadjuvant chemotherapy. The study population included 67 consecutive patients with non-small cell lung cancer (NSCLC) in stage II or III who were operated on at the Institute of Tuberculosis, Warsaw, Poland, between 20 April 2001 and 10 March 2003. All patients received two cycles of chemotherapy consisting of cisplatin and vinorelbine prior to the operation. The response to therapy was assessed as complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD), on the basis of CT scans performed before and after neoadjuvant chemotherapy. p53 and HER2/neu protein expression were evaluated by immunohistochemistry (IHC) using antibodies against p53 (clone PAb 1801, Novocastra) and against HER2/neu (Dako) in paraffin-embedded specimens of tumors. A response to therapy (CR+PR) was observed in 27 patients, while 40 patients (SD+PD) were regarded as resistant to therapy. Resistance was observed significantly more often in tumors above 3 cm in diameter. p53 expression was found in 16 tumors (23.9%) and HER2/neu in 26 tumors (38.8%). We observed a nonsignificant tendency to chemoresistance in tumors with HER-2/neu overexpression and also in tumors with p53 overexpression. If we consider HER-2/neu and p53 together, chemoresistance was observed statistically significantly more often when one or both markers were positive (p<0.05). This significance was independent of tumor size.
Prostate Cancer Progression and Surrounding Microenvironment
Authors: Alberti C.
Published: January 2018

Bidirectional cellular interactions between prostate cancer and prostate or bone stroma are needed for local tumor growth and distant metastasis. The genetics of cancer cells is affected by the host microenvironment and, reciprocally, permanent gene expression changes occur in the stroma surrounding epithelial cancer cells. The immune-mediated micromilieu also affects the progression of prostate cancer; the role of the immune system in controlling the growth of prostate cancer cells is complex, with immune escape mechanisms prevailing over effective antitumor response. Moreover, tumor stem cell models to explain the origin and progression of prostate cancer require appropriate environmental conditions. On the basis of a review of the literature, this article aims to outline the recent advances in the elucidation of the molecular mechanisms underlying the interactions between prostate cancer and its microenvironment.
Human Kallikrein 13 Expression in Salivary Gland Tumors
Authors: Darling M.R. , Jackson-Boeters L. , Daley T.D. , Diamandis E.P.
Published: January 2018

The human kallikrein 13 protein (hK13) is expressed in many normal tissues. Petraki et al have previously described presence of hK13 in salivary gland tissue, localized to duct epithelia and some acinar cells. The aim of this study was to determine whether hK13 is expressed in salivary gland tissues and salivary gland tumors (both benign and malignant), in order to compare normal with tumor tissues. Pleomorphic adenomas (PA), adenoid cystic carcinomas (ACC), polymorphous low grade adenocarcinomas (PLGA), acinic cell carcinomas (ACI), mucoepidermoid carcinomas (MEC) and adenocarcinomas not otherwise specified (ANOS) of both minor and major salivary glands were examined. The results of this study indicate that most salivary gland tumors show high levels of expression of hK13. Overall, staining in PA was significantly less than that seen in normal salivary gland tissue. PLGA, ACC and ANOS each stained significantly more than normal salivary gland tissue while MEC and ACI did not. Ductal cells and cells lining duct-like structures showed a higher intensity of staining than non-ductal cells in most tumors. Tumors which exhibited only non-ductal cells also exhibited cytoplasmic staining. In conclusion, we demonstrate the high expression of hK13 in several common salivary gland tumors.
Influence of Bicalutamide with or without Tamoxifen or Anastrozole on Insulin-like Growth Factor 1 and Binding Proteins in Prostate Cancer Patients
Authors: Boccardo F. , Rubagotti A. , Battaglia M. , Zattoni F. , Bertaccini A. , Romagnoli A. , Conti G.
Published: January 2018

Background

There is growing evidence that IGF-1 and binding proteins may be involved in prostate cancer promotion and progression.

Patients and methods

IGF-1 and binding proteins (IGFBP-1 and 3) serum levels were measured at baseline and after 3 and 6 months of treatment in a selected group of patients with prostate cancer who were randomly assigned to treatment with bicalutamide, bicalutamide plus anastrozole or bicalutamide plus tamoxifen in a comparative study investigating the role of pharmacological medication in the development of bicalutamide-induced gynecomastia.

Results

Bicalutamide monotherapy does not appear to alter the IGF-1/IGFBP system. In fact, the increase in IGF-1 levels induced by this treatment was paralleled by comparable increases in binding protein (IGFBP-3). No major changes from baseline up to month 6 either in IGF-1 or in IGFBP-1 and 3 were observed in the bicalutamide plus anastrozole arm. The addition of tamoxifen to bicalutamide produced a sharp decrease in IGF-1 levels (p<0.001) coupled with an increase in both IGFBP-1 (p=0.001) and, to a lesser extent, IGFBP-3 (p=0.5).

Conclusions

The concurrent administration of tamoxifen and bicalutamide reduces the synthesis and bioavailability of IGF-1. Moreover, increased binding protein levels might exert antiproliferative and proapoptotic effects on prostate cancer cells, independently of the IGF-1/IGF receptor-mediated survival system. Both effects might have a synergistic inhibitory influence on prostate cancer growth.
Clinical Utility of Determination of HER-2/neu and EGFR Fragments in Serum of Patients with Metastatic Breast Cancer
Authors: Witzel I. , Thomssen C. , Krenkel S. , Wilczak W. , Bubenheim M. , Pantel K. , Neumann R. , Jänicke F. , Müller V.
Published: January 2018

Introduction

The growth factor receptors EGFR and HER-2/neu are targets for new treatment strategies and are of potential use as prognostic and predictive factors. However, the optimal method of determination in order to obtain clinically relevant information remains a source of controversy.

Methods

HER-2/neu and EGFR expression was examined by immunohistochemistry in primary tumors of patients with breast cancer. In addition, serum was tested for the extracellular domains of HER-2/neu (HER-2/neu ECD) and EGFR (sEGFR) before initiation of therapy for metastatic disease (n=76). The course of disease from the time of metastasis with regard to these parameters was evaluated by univariate and multivariate analyses.

Results

HER-2/neu ECD levels at the time of metastatic disease were correlated with HER-2/neu expression determined by immunohistochemistry from primary tumors (p=0.001). No correlation was observed between expression of EGFR in primary tumors and sEGFR serum levels. HER-2/neu ECD and sEGFR levels at the onset of metastatic disease did not show a significant impact on overall survival.

Conclusions

Determination of HER-2/neu ECD levels in the serum measured by ELISA at the onset of metastatic disease could offer an alternative to immunohistochemistry of the primary tumor since serum levels are correlated with protein expression in primary tumors. In contrast, no such correlation was observed for EGFR.
Pre-Treatment Prediction of Chemoresistance in Second-Line Chemotherapy of Ovarian Carcinoma: Value of Serological Tumor Marker Determination (Tetranectin, YKL-40, CASA, CA 125)
Authors: Gronlund B. , Høgdall E.V.S. , Christensen I.J. , Johansen J.S. , Nørgaard-Pedersen B. , Engelholm S.A. , Høgdall C.
Published: January 2018

Objective

To examine if the determination of the levels of serological tumor markers at time of relapse had any predictive value for chemoresistance in the second-line treatment of ovarian cancer patients.

Methods

From a registry of consecutive single-institution patients with epithelial ovarian carcinoma pretreated with paclitaxel plus platinum, we selected 82 patients with (a) solid tumor recurrence, and (b) second-line chemotherapy consisting of topotecan (platinum-resistant disease) or paclitaxel plus carboplatin (platinum-sensitive disease). Stored serum samples were analyzed for the biochemical tumor markers tetranectin, YKL-40, CASA (cancer-associated serum antigen), and CA 125. The serum tumor marker levels at time of relapse were correlated with response status at landmark time after 4 cycles of second-line chemotherapy. Univariate and multivariate logistic regression analyses (chemoresistant vs non-chemoresistant disease) were performed.

Results

At landmark time, 26% of patients had progression according to the GCIG (Gynecologic Cancer Intergroup) progression criteria. In univariate logistic regression analysis, the tumor markers tetranectin (OR 0.4; 95% CI: 0.2–0.8; p=0.008), YKL-40 (OR 1.8; 95% CI: 1.0–3.3; p=0.045), and CASA (OR 1.8; 95% CI: 1.2–2.7; p=0.007) had predictive value for second-line chemoresistance, whereas serum CA 125 had no predictive value. In a multivariate logistic regression analysis, serum tetranectin and CASA both had independent predictive value for chemoresistance. The combined determination of tetranectin and CASA had a specificity of 90% with 33% sensitivity for the prediction of chemoresistance (area under the receiver operating characteristic curve = 0.78; 95% CI: 0.66–0.91; p=0.001).

Conclusion

Low serum levels of tetranectin, or high serum levels of CASA or YKL-40, are associated with increased risk of second-line chemoresistance in patients with ovarian cancer.
HPV Testing and Pap Test: Role for a Combined Approach in a Non-Screened Population
Authors: Marchetti I. , Zavaglia K. , Bertacca G. , Aretini P. , Matteoli B. , Viacava P. , Prato B. , De Punzio C. , Genazzani A.R. , Bevilacqua G. , Di Coscio G.
Published: January 2018

The aim of the present study was to test the polymerase chain reaction (PCR) as a tool to identify human papillomavirus (HPV) in routine cytological samples scraped from the uterine cervix. Moreover, attention has been focused on the correlation between HPV types and early intraepithelial lesions. The study involved 586 women who had undergone conventional Pap test. Analysis of HPV infection was performed by PCR and HPV typing by dot blot. In a group of 78 cases histologically diagnosed as high-grade squamous intraepithelial lesions (HSILs), the cytological diagnosis was correct in 92.3% and the HPV test was positive in 89.8% of cases; combined positivity at Pap and/or HPV tests raised this figure to 99.0%. In a group of 67 cases histologically diagnosed as low-grade squamous intraepithelial lesions (LSILs), the cytological diagnosis was correct in 73.1% and the PCR-based HPV test was positive in 64.2%; combined positivity at Pap and/or HPV tests raised this figure to 91.0%. This study confirms the limitations of screening programs based on Pap test only. Our results suggest, in fact, that adding the HPV test to primary screening could increase the yield of preinvasive cervical lesions.
Urinary Neopterin in Patients with Advanced Colorectal Carcinoma
Authors: Melichar B. , Solichová D. , Melicharová K. , Malířová E. , Cermanová M. , Zadák Z.
Published: January 2018

In previous studies, mostly in patients with early stage colorectal carcinoma, neopterin, an indicator of systemic immune activation, has been associated with poor prognosis. The aim of the present study was to evaluate urinary neopterin in patients with advanced or metastatic colorectal carcinoma treated with chemotherapy. A retrospective analysis was performed of urinary neopterin, determined by high-performance liquid chromatography, in 88 patients with advanced or metastatic colorectal carcinoma. Peripheral blood cell count and serum carcinoembryonic antigen (CEA) were determined in 72 patients before the start of chemotherapy. Urinary neopterin in colorectal carcinoma patients was significantly increased compared to controls, but lower than in patients with inflammatory bowel disease. Neopterin correlated significantly with serum CEA, age, peripheral blood leukocyte and platelet counts. The median survival of colorectal carcinoma patients with urinary neopterin below 214 μmol/mol creatinine was significantly longer compared to that of patients with higher neopterin concentrations (median 18 vs 5 months, log-rank test p=0.003). CEA and hemoglobin were also associated with survival in univariate analysis, but in multivariate analysis only urinary neopterin and serum CEA were independent predictors of survival. High urinary neopterin during follow-up was also predictive of poor prognosis.