bluuebunny/crossref_metadata_2025_split huggingface dataset:
Behavior of free Testosterone in Patients with Prostate Cancer on Androgen Deprivation Therapy
Authors: Morote J. , Esquena S. , Abascal J.M. , Trilla E. , Cecchini L. , Raventós C.X. , Catalín R. , Reventós J. 
Published: January 2018

Objectives Determination of free testosterone (FT) serum level is an efficient method to evaluate bioavailable testosterone. We analyzed the behavior of serum FT in patients with prostate cancer receiving androgen deprivation therapy (ADT) and correlated FT with total testosterone (TT). We also analyzed the efficiency of both isoforms in the evaluation of the ADT. Methods Serum levels of TT and FT were determined in 191 patients with prostate cancer in a cross-sectional study. A subset of 56 patients submitted only to radical prostatectomy served as control group. The remaining 135 patients with advanced prostate cancer on three-month LHRH agonist treatment comprised the study group. The median age of the population was 73 years (range, 53–86 years) and the median time on ADT was 42 months (6–198). Results A significant correlation and linear regression between TT and FT was observed (r2 0.948). The efficiency of TT and FT to discriminate patients with and without ADT was similar (AUC: 0.993 and 0.995, respectively, p>0.05). A castration level of serum FT established at 1.7 pg/mL had a sensitivity of 85.9% and a specificity of 100%, which are similar to the sensitivity and specificity of 50 ng/dL of TT. All patients without ADT had levels of serum TT and FT above the castration level. In 19 of the 135 (14.1%) patients on ADT serum TT was above 50 ng/dL. In 12 of these 19 patients (63.2%) serum FT was below 1.7 pg/mL while in seven patients (5.2%) FT was also above the castration level. Conclusions The castration level of FT was established at 1.7 pg/mL. Serum TT and TF correlated very well; however, they seemed to provide complementary information in the evaluation of ADT efficiency. 14.1% of the patients on ADT failed to reach the castration level of serum TT; determination of serum FT in these patients would reduce this rate to 5.2%.
Neuroendocrine Phenotype of Non-Small Cell Lung Carcinoma: Immunohistological Evaluation and Biochemical Study
Authors: Slodkowska J. , Zych J. , Szturmowicz M. , Demkow U. , Rowinska-Zakrzewska E. , Roszkowski-Sliz K. 
Published: January 2018

Aims and methods The prevalence and distribution of neuroendocrine differentiation in non-small cell lung cancer (NSCLC) was estimated by assays for synaptophysin (SYN), chromogranin A (CgA), Leu7 and neuron-specific enolase (NSE). Serum NSE and CgA were determined in parallel to find the values of these markers for distinguishing neuroendocrine differentiation in NSCLC. Fifty-eight resected NSCLC specimens and 34 sera of NSCLC patients entered the study. Neuroendocrine differentiation was graded according to the percentage of neuroendocrine tumor cells as NE0 – 0%, NE1–NE4 – 1%->76%. Serum NSE <12.5 ng/mL and serum CgA <46 U/L were taken as cutoff levels. Results 63.8% (37/58) of NSCLC were scored as NE1–NE4 according to the SYN, CgA and Leu7 levels; 34.5% as NE1; 29.3% as NE2–NE4. 56.8% of tumors were positive for SYN, 34.4% for CgA, 22.4% for Leu7, and 79.3% for NSE. A significant relationship was found between tumor SYN and tumor CgA expression, and between tumor SYN expression and tumor stage. Adenocarcinomas showed a significantly higher rate of neuroendocrine differentiation than squamous cell carcinomas. All normal serum CgA levels corresponded to a lack of CgA expression in the tumors. The increased serum NSE levels presented by 26% of NSCLC patients (mainly <16 ng/mL) did not correlate with tumor NSE expression. Conclusions The prevalence of neuroendocrine differentiation in NSCLC varies and depends on the immunohistochemical criteria used; this warrants standardization of the immunohistochemical criteria for neuroendocrine differentiation in NSCLC. NSE expression in the tumor and a mild increase in serum NSE are poor markers for distinguishing neuroendocrine differentiation in NSCLC.
Collagenase-3 (MMP-13) Expression in Cutaneous Malignant Melanoma
Authors: Corte M.D. , Gonzalez L.O. , Corte M.G. , Quintela I. , Pidal I. , Bongera M. , Vizoso F. 
Published: January 2018

Background Matrix metalloproteases (MMPs), enzymes with the ability to degrade the extracellular matrix, play an important role in tissue invasion by cutaneous malignant melanoma (CMM). One specific MMP, collagenase-3 (MMP-13), is thought to have a key function in the activation of MMP. Aims To evaluate the expression of MMP-13 in CMM and assess its possible relationship to clinical and pathological parameters. Methods MMP-13 expression was analyzed in 51 paraffin-embedded tumor samples from patients with invasive CMM, ten samples from in situ melanomas, and in eight samples from benign lesions (three dermal melanocytic nevi, three compound melanocytic nevi and two atypical melanocytic nevi) using immunohistochemical techniques. The median follow-up period in patients with invasive CMM was 50 months. Results Benign lesions were consistently negative for MMP-13, whereas three of the ten in situ melanomas (30%) and 23 of the 51 invasive CMMs (45%) showed positive immunostaining for MMP-13. The percentage of MMP-13-positive tumors correlated significantly and positively with the mitotic index (p=0.002) in invasive CMM. However, our results did not show any significant association between tumoral MMP-13 expression and relapse-free survival in patients with invasive CMM. Conclusions MMP-13 appears to be a factor associated with tumor aggressiveness in CMM. It seems to eliminate an important barrier not only against tumoral invasion but also against proliferation.
Prognostic Biomarkers in Renal Cell Carcinoma: Relevance of DNA Ploidy in Predicting Disease-Related Survival
Authors: Pinto A.E. , Monteiro P. , Silva G. , Ayres J.V. , Soares J. 
Published: January 2018

Objective To investigate the prognostic value of DNA ploidy, Ki-67 index and p53 expression in relation to disease-related survival in a consecutive series of patients with renal cell carcinoma (RCC). Material and methods The study group consisted of 64 RCC patients treated by radical nephrectomy. Histological type, pathological staging and nuclear anaplasia were assessed according to the WHO classification, TNM system and Fuhrman grading criteria, respectively. Ploidy was determined by DNA flow cytometry using two sampling methods (frozen vs paraffin-embedded tissue). Ki-67 and p53 were evaluated by immunohistochemistry techniques using two cutoff points (10% vs mean value) for staining interpretation. Kaplan-Meier and Cox regression analyses were used for prognostic evaluation. Results Thirty-one tumors (48.4%) showed DNA diploidy and 33 (51.6%) were DNA aneuploid. Concordance between both ploidy measurement methods was found in 85.5% of cases (p=0.0455). The mean values for Ki-67 and p53 immunostaining were 3.65% (0–23.5%) and 5.90% (0–55.9%), respectively. DNA ploidy significantly correlated with staging, tumor size (pT), nuclear grading, and Ki-67 (mean value cutoff). Ki-67 (10% cutoff) correlated with staging and pT, while p53 (mean value cutoff) was associated with Ki-67 (mean value cutoff). There were significant differences between survival curves for pathological stage, pT, nuclear grade, ploidy, Ki-67 (both cutoffs), and p53 (10% cutoff). By univariate regression analysis, stage III and stage IV, pT3, aneuploidy, high Ki-67 (both cutoffs), and p53 overexpression (10% cutoff) showed significant correlations with worse disease-related survival. In addition, DNA aneuploidy significantly correlated with poor prognosis within stages I/II (p=0.0355) and stages III/IV (p=0.0138) of the disease. Conclusion The results indicate that DNA ploidy has relevant prognostic value in RCC, adding useful information to the classic histopathological indicators of clinical outcome.
Levels of Circulating Cell-Free Serum DNA in Benign and Malignant Breast Lesions
Authors: Zanetti-Dällenbach R.A. , Schmid S. , Wight E. , Holzgreve W. , Ladewig A. , Hahn S. , Zhong X.Y. 
Published: January 2018

Purposes of the study: We analyzed circulating cell-free DNA in the serum of patients with benign and malignant breast disease and in healthy individuals to determine its diagnostic value. Basic procedures: Serum samples were obtained from 50 healthy individuals, 33 patients with malignant breast disease and 32 patients with benign breast disease. Circulatory DNA was extracted from serum samples. Cell-free DNA was quantified by real-time quantitative PCR for the glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene. Tissue samples from patients with malignant and benign breast lesions were histopathologically examined. Main findings: The mean levels of circulating cell-free DNA in serum samples were 41,149 genome equivalents (GE)/mL in patients with malignant disease, 30,826 GE/mL in patients with benign disease, and 13,267 GE/mL in healthy individuals. Healthy individuals had significantly lower levels of cell-free DNA than patients with malignant or benign breast disease (p=0.001, p=0.031). No significant difference was observed between malignant and benign disease. There was a correlation between cell-free DNA levels and tumor size but not with other tumor characteristics. Principal conclusion: Our results suggest that levels of circulating cell-free DNA in serum could have diagnostic value to discriminate between healthy individuals and patients with breast lesions but not between patients with malignant and benign breast lesions.
Cytoplasmic Localization of BAG-1 in Leukoplakia and Carcinoma of the Tongue: Correlation with p53 and C-Erbb2 in Carcinoma
Authors: Vora H.H. , Mehta S.V. , Shah K.N. , Brahmbhatt B.V. , Desai N.S. , Shukla S.N. , Shah P.M. 
Published: January 2018

Background The present study evaluated the clinical significance of BAG-1, an antiapoptotic protein, in leukoplakia and carcinoma of the tongue. Methods BAG-1 expression was evaluated by immunohistochemistry in paraffin-embedded tissues of leukoplakia (n=25) and carcinoma of the tongue (n=61). Results Cytoplasmic expression was predominantly seen in 80% and 70% of patients with leukoplakia and carcinoma, respectively. BAG-1 expression was found to be significantly lower in tobacco users than in non-tobacco users. BAG-1 expression in tobacco-using leukoplakia and carcinoma patients was compared by grouping the carcinoma patients according to lymph node status and disease stage. Carcinoma patients with tumor-positive lymph nodes had significantly lower BAG-1 expression than patients with negative lymph nodes and leukoplakia. Further, a trend towards an inverse correlation was observed with p53 and c-erbB2. In univariate and multivariate survival analysis, patient subgroups with 2+ or 3+ marker positivity (BAG-1 negativity, p53 and c-erbB2 positivity) had a reduced overall survival compared with patient subgroups with 1+ marker positivity or negativity. Conclusion BAG-1 negativity in association with p53 and c-erbB2 positivity identified a subgroup of tongue cancer patients with an aggressive phenotype. Hence, an antiapoptotic protein, BAG-1, was found to be down-regulated in chewing-tobacco-mediated tongue carcinogenesis.
Nuclear and Cytoplasmic Expression of ErbB-4 in Prostate Cancer
Authors: Ben-Yosef R. , Sarid D. , Vexler A. , Lidawi G. , Inbar M. , Marmor S. , Starr A. , Hahoshen N. Yaal 
Published: January 2018

Purpose To evaluate cytoplasmic and nuclear ErbB-4 expression in prostate cancer specimens and its association with outcome. Basic procedures Specimens of 50 prostate cancer patients were investigated for ErbB-4 overexpression using immunohistochemistry staining. Cytoplasmic and nuclear staining was graded as 0–3 according to its intensity. The prognostic parameters were tumor stage, PSA level, Gleason score, probability of positive lymph nodes (Partin's tables and Roach equation), and 5-year disease free survival (Kattan nomogram). Main findings Overexpression of ErbB-4 (≥1) was detected in 30 (60%) patients and overexpression using cytoplasmic and nuclear staining was ≥2 in 19 (38%) and 17 (34%) patients, respectively. In only one third of the specimens was there any similarity between the 2 types of staining. Advanced tumor stage, high pretreatment PSA levels and high Gleason scores were evenly distributed among the patients with low (≤1) and intermediate/high (≥2) ErbB-4 expression. The probability of lymph node involvement and 5-year disease free survival were similar in both types of staining. Principal conclusions ErbB-4 was overexpressed (cytoplasmic and nuclear staining) in approximately one third of prostate cancer patients. The rate of similarity between the 2 staining types was only 33%: overexpression was evenly distributed among intermediate/high and low risk prostate cancer patients with both staining methods.
Prognostic Significance of TP53 Mutations in Oral Squamous Cell Carcinoma with Human Papilloma virus Infection
Authors: Kozomara R.J. , Brankovic-Magic M.V. , Jovic N.R. , Stosic S.M. , Magic Z.M. 
Published: January 2018

Purpose The aim of this study was to analyze the prognostic impact of mutated TP53 in patients with oral squamous cell carcinoma (OSCC) whose tumors were infected with human papillomavirus (HPV). Methods Thirty-two HPV-positive OSCC patients were included. Most of them were clinically classified as stage III (n=29). All patients underwent postoperative radiotherapy (follow-up from 12 to 60 months, median 32). There were 21 relapses. DNA was isolated by phenol extraction from tumor tissue. HPV DNA (type 16, 18, 31, 33) was detected in genomic DNA of the tumors by the PCR-PAGE method. TP53 mutations (exons 4–8) were detected by the PCR-SSCP method. Results A statistically significant difference in the number of relapses in HPV-infected (13/21) versus HPV-infected and TP53-mutated (8/8) patients was observed. Patients with both TP53 mutation and HPV infection had a significantly shorter disease-free interval than patients with HPV infection only (median 6 versus 31 months, respectively). Conclusions TP53 mutations are associated with a higher risk of relapse and contribute to an even worse prognosis of patients with OSCC when the tumors are HPV infected. The shorter disease-free interval in patients with TP53 mutations indicates that the response to postoperative radiotherapy may be influenced by TP53 status. The presence of both HPV infection and TP53 mutations may define a particular group of tumors with a more aggressive phenotype in advanced OSCC.
CYP1A1 *2B and *4 Polymorphisms are associated with Lung Cancer Susceptibility in Mexican Patients
Authors: Gallegos-Arreola M.P. , Figuera-Villanueva L.E. , Troyo-Sanroman R. , Morgán-Villela G. , Puebla-Pérez A.M. , Flores-Marquez M.R. , Zúñiga-González G.M. 
Published: January 2018

Background CYP1A1 is a gene involved in the high aryl hydrocarbon hydroxylase -inducible phenotype, which is a genetically-determined variation among individuals that has been associated with lung cancer risk. More specifically, CYP1A1*2B and *4 polymorphisms have been associated with high susceptibility to lung cancer among cigarette smokers. Materials and methods: DNA was obtained from blood samples and we studied by PCR-RFLP the distribution of CYP1A1*2B (n=248) and *4 (n=222) polymorphisms in healthy controls and 222 lung cancer patients from a Mexican population. Results Comparisons between groups showed an increased risk for lung cancer patients of *2B/*2B (18%; OR 7.6; 95% CI 3.0–19.2) and *4/*4 genotypes (15%; OR 11.45; 95% CI 2.19–59.85) compared to the control group (1% for *2B/*2B and 4.4% for *4/*4). A significant association between lung cancer and homozygous *2B/*2B passive smokers and *4/*4 ever (cigarettes) and passive smokers was also observed (p<0.05). Multivariate analysis revealed an increased risk for the *2B/2B genotype (OR 6.83), as well as for *4/*4 (OR 28.8). Conclusion The results of the study indicate a significant association between *2B/*2B and *4/*4 genotypes and the risk of developing lung cancer among Mexicans.
Antiphospholipid Antibodies and Acute-Phase Response in Non-Metastatic Colorectal Cancer Patients
Authors: Battistelli S. , Stefanoni M. , Petrioli R. , Genovese A. , Dell'Avanzato R. , Donati G. , Vittoria A. , Roviello F. 
Published: January 2018

Aim To investigate the plasma levels and prevalence of the most common antiphospholipid antibodies, as well as their relationships with several plasma markers of inflammation, in order to characterize some aspects of cancer thrombophilia. Materials and methods Eighty-three cancer patients with non-metastatic colorectal solid tumors and 94 control subjects were tested for the presence of IgG/IgM/IgA anti-cardiolipin and anti-β2-glycoprotein I antibodies and of several acute-phase reactants, i.e., fibrinogen, factor VIII:C and C4b-binding protein. Results In cancer patients the plasma levels of the acute-phase reactants and the IgA/IgG anti-cardiolipin and IgA anti-β2-glycoprotein I antibodies were significantly higher; the acute-phase reactants were significantly correlated with anti-cardiolipin antibodies; the prevalence of antiphospholipid antibodies was not significantly higher. Conclusions In patients with non-metastatic colorectal cancer the acute-phase response is associated with antiphospholipid generation. This could represent a further pathogenetic mechanism for the short-term post-surgery thrombotic complications of patients with colorectal cancer.
Coagulation Factor Levels in Non-Metastatic Colorectal Cancer Patients
Authors: Battistelli S. , Stefanoni M. , Lorenzi B. , Dell'Avanzato R. , Varrone F. , Pascucci A. , Petrioli R. , Vittoria A. 
Published: January 2018

There is evidence that high plasma levels of factor (F) VIII, FIX, FXI and fibrinogen are independent risk factors for venous thromboembolism. Aim To determine the plasma concentrations of several coagulation factors and C4b-binding protein (C4BP) in a group of patients with non-metastatic colorectal cancer in order to investigate some aspects of cancer-acquired thrombophilia. Methods: Plasma fibrinogen, FII, FV, FVII, FVIII, FIX, FX, FXI and FXII activity levels and C4BP concentrations were determined in 73 patients with non-metastatic colorectal cancer (48 colon and 25 rectum) and in 67 matched control subjects. No one in either group had had previous thrombotic events. Results Mean plasma concentrations of fibrinogen (functional and antigen), FVIII, FIX, FV and C4BP were significantly higher in colorectal cancer patients than in control subjects, while FVII and FXII levels were significantly decreased. Several correlations were found between the increased coagulation factors and C4BP concentrations, while FVII was highly correlated with FXII. Conclusions In colorectal cancer patients high plasma fibrinogen, FVIII and FIX levels might represent further risk factors for venous thrombotic complications in the immediate post-surgery period, while decreased FVII and FXII concentrations may be an index of intravascular coagulation activation, still in a subclinical phase.
TP53 Mutations in Breast Cancer: Association with Ductal Histology and Early Relapse of Disease
Authors: Brankovic-Magic M.V. , Jankovic R.N. , Dobricic J.D. , Borojevic N.D. , Magic Z.M. , Radulovic S.S. 
Published: January 2018

Purpose This study aimed to investigate the incidence of core domain TP53 mutations in Serbian breast cancer patients in view of their possible correlation with prognostic parameters, tumor characteristics and clinical disease course. Methods 145 breast cancer patients were included. Data on clinical disease course were available for 100 patients including 30 node-negative and 70 node-positive patients. After surgery, node-positive patients underwent adjuvant chemotherapy, mostly CMF. TP53 mutations were detected by PCR-SSCP. Results 31 mutations were found in 27/145 patients including 4/59 node-negative patients and 23/83 node-positive patients (4 double mutations). 26/31 TP53 mutations were found in patients with invasive ductal carcinoma and only 2 in patients with invasive lobular carcinoma. The presence of TP53 mutations was correlated with clinical disease course in premenopausal node-positive patients (n=70). 11/20 patients with TP53 mutations relapsed. Within the first 24 months of follow-up, significantly shorter disease-free intervals were observed in TP5. 3-mutated patients. Conclusions TP53 mutations correlated only with nodal status and ductal histology. The significance of the predominant distribution of TP53 mutations in tumors with a ductal histology for the aggressive behavior of these tumors has yet to be proved, since the favorable biological features of tumors with a lobular histology do not result in a better prognosis. Early relapse in mutated- TP5. 3 carriers may support data on its predictive value with respect to adjuvant CMF.
Circulating Tumor Cells in HER-2 Positive Metastatic Breast Cancer Patients Treated with Trastuzumab and Chemotherapy
Authors: Nunes Raquel A. , Li Xiaochun , Kang Soonmo Peter , Burstein Harold , Roberts Lisa , Carney Walter , Blackwell Kimberly , Ryan Paula , Borges Virginia , Iglehart J. Dirk , Friedman Paula , Harris Lyndsay N. 
Published: January 2018

The detection of circulating tumor cells (CTCs) in peripheral blood may have important prognostic and predictive implications in breast cancer treatment. A limitation in this field has been the lack of a validated method of accurately measuring CTCs. While sensitivity has improved using RT-PCR, specificity remains a major challenge. The goal of this paper is to present a sensitive and specific methodology of detecting CTCs in women with HER-2-positive metastatic breast cancer, and to examine its role as a marker that tracks disease response during treatment with trastuzumab-containing regimens. The study included patients with HER-2-positive metastatic breast cancer enrolled on two different clinical protocols using a trastuzumab-containing regimen. Serial CTCs were measured at planned time points and clinical correlations were made. Immunomagnetic selection of circulating epithelial cells was used to address the specificity of tumor cell detection using cytokeratin 19 (CK19). In addition, the extracellular domain of the HER-2 protein (HER-2/ECD) was measured to determine if CTCs detected by CK19 accurately reflect tumor burden. The presence of CTCs at first restaging was associated with disease progression. We observed an association between CK19 and HER-2/ECD. The association of HER-2/ECD with clinical response followed a similar pattern to that seen with CK19. Finally, the absence of HER-2/ECD at best overall response and a change of HER-2/ECD from positive at baseline to negative at best overall response was associated with favorable treatment response. Our study supports the prognostic and predictive role of the detection of CTCs in treatment of HER-2-positive metastatic breast cancer patients. The association between CK19 and markers of disease burden is in line with the concept that CTCs may be a reliable measure of tumor cells in the peripheral blood of patients with metastatic breast cancer. The association of CTCs at first restaging with treatment failure indicates that CTCs may have a role as surrogate markers to monitor treatment response.