bluuebunny/crossref_metadata_2025_split huggingface dataset:
Central venous catheterization for acute trauma resuscitation: Tip position analysis using routine emergency computed tomography
Authors: Struck Manuel F , Ewens Sebastian , Schummer Wolfram , Busch Thilo , Bernhard Michael , Fakler Johannes K M , Stumpp Patrick , Stehr Sebastian N , Josten Christoph , Wrigge Hermann 
Published: March 2018

Purpose: Central venous catheter insertion for acute trauma resuscitation may be associated with mechanical complications, but studies on the exact central venous catheter tip positions are not available. The goal of the study was to analyze central venous catheter tip positions using routine emergency computed tomography. Methods: Consecutive acute multiple trauma patients requiring large-bore thoracocervical central venous catheters in the resuscitation room of a university hospital were enrolled retrospectively from 2010 to 2015. Patients who received a routine emergency chest computed tomography were analyzed regarding central venous catheter tip position. The central venous catheter tip position was defined as correct if the catheter tip was placed less than 1 cm inside the right atrium relative to the cavoatrial junction, and the simultaneous angle of the central venous catheter tip compared with the lateral border of the superior vena cava was below 40°. Results: During the 6-year study period, 97 patients were analyzed for the central venous catheter tip position in computed tomography. Malpositions were observed in 29 patients (29.9%). Patients with malpositioned central venous catheters presented with a higher rate of shock (systolic blood pressure <90 mmHg) at admission (58.6% vs 33.8%, p = 0.023) and a higher mean injury severity score (38.5 ± 15.7 vs 31.6 ± 11.8, p = 0.041) compared with patients with correctly positioned central venous catheter tips. Logistic regression revealed injury severity score as a significant predictor for central venous catheter malposition (odds ratio = 1.039, 95% confidence interval = 1.005–1.074, p = 0.024). Conclusion: Multiple trauma patients who underwent emergency central venous catheter placement by experienced anesthetists presented with considerable tip malposition in computed tomography, which was significantly associated with a higher injury severity.
DNA Chips: The Future of Biomarkers
Authors: de Benedetti V.M.G. , Biglia N. , Sismondi P. , de Bortoli M. 
Published: March 2018

DNA chips are small, solid supports such as microscope slides onto which thousands of cDNAs or oligonucleotides are arrayed, representing known genes or simply EST clones, or covering the entire sequence of a gene with all its possible mutations. Fluorescently labeled DNA or RNA extracted from tissues is hybridized to the array. Laser scanning of the chip permits quantitative evaluation of each individual complementary sequence present in the sample. DNA chip technology is currently being proposed for qualitative and quantitative applications, firstly for the detection of point mutations, small deletions and insertions in genes involved in human diseases or affected during cancer progression; secondly, to determine on a genome-wide basis the pattern of gene expression in tumors, as well as in a number of experimental situations. The extraordinary power of DNA chips will have a strong impact on medicine in the near future, both in the molecular characterization of tumors and genetic diseases and in drug discovery and evaluation. Quantitative applications will soon spread through all fields of biology.
Molecular Detection of Codon 12 K-RAS Mutations in Circulating DNA from Serum of Colorectal Cancer Patients
Authors: Salbe C. , Trevisiol C. , Ferruzzi E. , Mancuso T. , Nascimbeni R. , Di Fabio F. , Salerni B. , Dittadi R. 
Published: March 2018

Point mutations of the K-RAS gene at codon 12 are found in about 40% of cases with colorectal cancer. The diagnostic implications of the detection of these mutations and their clinical utility are still unclear. The aim of this study was to test both the feasibility of the detection of the mutated K-RAS gene in serum and its potential role in colorectal cancer detection and monitoring. Codon 12 K-RAS mutations were examined in DNA extracted from the serum of 35 patients with colorectal cancer and were compared with the K-RAS status in the corresponding primary tumor. Molecular detection was performed by the mutant-enriched PCR (ME-PCR) assay, a sensitive method capable of distinguishing a small quantity of mutated DNA in the presence of abundant wild-type DNA. The occurrence of mutations was compared with clinicopathological parameters as well as CEA and CA19.9 serum levels. We found codon 12 K-RAS mutations in the tissue of 13/35 (37%) patients. Serum mutations were detected in 5/13 (38.5%) patients with mutated K-RAS in the tissue. 26/35 (74%) patients showed an identical K-RAS pattern in tissue and serum. No codon 12 K-RAS alterations were found in serum samples of 22 patients with benign gastrointestinal diseases. Elevated serum CEA levels were detected in 16 patients, four of whom also presented serum RAS mutations. Our results confirm that K-RAS mutations can be found in circulating DNA extracted from serum samples of patients with colorectal cancer and show that there is a correspondence between serum and tissue K-RAS patterns.
The Prognostic Value of the Tumor Marker CA 15–3 at Initial Diagnosis of Patients with Breast Cancer
Authors: McLaughlin R. , McGrath J. , Grimes H. , Given H.F. 
Published: March 2018

CA 15–3 has been most widely used as a serum tumor marker in follow-up and detection of breast cancer recurrence. In this study we have specifically focused upon the prognostic implications and utility of preoperative CA 15–3 levels. We have identified on our database 414 patients with breast cancer in whom serial levels of the serum tumor marker CA 15–3 had been determined at diagnosis and follow-up. We have analyzed the follow-up and clinical outcomes in these patients and from this data we have assessed the potential of CA 15–3 as a predictor of five-year overall and disease-free survival. Our results show that an initially elevated CA 15–3 level is associated with a very poor prognosis in both early and late stage disease. Elevated pre-biopsy CA 15–3 levels are associated with 14% five-year disease-free survival rates and 17% overall survival rates at five years. In contrast, normal CA 15–3 levels are associated with 47% five-year disease-free survival rates and 54% overall survival rates at five years (p<0.01). Comparison of five-year survival rates between patients with elevated and normal CA 15–3 levels in early breast cancer (stage I and II) also showed significant differences, with survival being 41% and 75%, respectively (p<0.01).
Circulating Angiogenesis Regulators in Cancer Patients
Authors: Kuroi K. , Toi M. 
Published: March 2018

Background/Aims To date, numerous studies have demonstrated that several angiogenesis regulators circulate in the blood and may function as endocrine factors in cancer patients. This review aims to give a comprehensive insight into the possible clinical value of circulating angiogenesis regulators, mainly basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF), angiogenin, pleiotrophin, thrombospondin (TSP) and endostatin (ES) in cancer patients. Methods A computerized (MEDLINE) and a manual search based on the reference lists of the publications were performed to identify articles published on this topic. Results In a detailed literature search, approximately 100 publications were found up to the end of 1999. Circulating angiogenic factors such as bFGF, VEGF, HGF and angiogenin have been evaluated not only as diagnostic and/or prognostic factors but also as predictive factors in cancer patients. On the other hand, little is known about the clinical significance of negative regulators. Neither the source nor the mechanism of protein externalization has been clarified in detail. Conclusions Although there are no known factors with established clinical utility, circulating angiogenesis regulators may be useful in several situations. They could be used to determine the risk of developing cancer, to screen for early detection, to distinguish benign from malignant disease, and to distinguish between different types of malignancies. In patients with established malignancies such factors might be used to determine prognosis, to predict the response to therapy, and to monitor the clinical course. Further investigations are warranted to assess the specific utility of each factor.
Relationship between Mesenteric and Peripheral Blood Levels of CA 19-9 in Patients with Colorectal Cancer
Authors: Forones N. M. , Tanaka M. , Matos D. 
Published: March 2018

Introduction CA19-9 is one of the most important tumor markers used in patients with colorectal cancer, mainly in radical surgery follow-up. Aim: The purpose of this study was to evaluate the preoperative CA19-9 level obtained from a peripheral vein (PV) and compare it to the level obtained from the mesenteric vein (MV). Materials and methods Blood was collected from a PV of the arm and from the MV of 59 patients with colorectal cancer before primary surgery. Of these 59 patients fourteen had stage I disease, 10 stage II, 22 stage III, and 13 stage IV. CA19-9 was determined in serum by immunoenzymatic assay (Abbott Diagnostica). Results Fifteen patients (24%) had elevated serum levels of CA19-9 in the MV and 13 (22%) in the PV. None of the stage I or II patients had elevated serum levels of CA19-9. There were no differences between marker levels in blood collected from the MV or PV, independent of clinical stage. The CA19-9 values obtained from the MV differed significantly in the different stages of the disease according to the Kruskal-Wallis analysis (p=0.026); this difference was not statistically significant (p=0.08) in serum from the PV. There was no correlation between venous infiltration by the tumor and positivity of CA19-9 serum levels collected from the mesenteric vein. We observed a close correlation between the serum levels of CA19-9 collected from the PV and from the MV (r=0.9). Conclusion The current study demonstrates a close correlation between the serum levels of CA19-9 collected from a peripheral vein and from the mesenteric vein. Our results confirmed the poor sensitivity of serum CA19-9 at diagnosis, independent of the collection site.
Loss of Heterozygosity on Chromosomes 1, 2, 8, 9 and 17 in Cerebral Atherosclerotic plaques
Authors: Miniati P. , Sourvinos G. , Michalodimitrakis M. , Spandidos D.A. 
Published: March 2018

Objective Atherosclerosis is a fibroproliferative disease which has been attributed to several factors including genetic and molecular alterations. Initial studies have shown genetic alterations at the microsatellite level in the DNA of atherosclerotic plaques. Extending our initial findings, we performed a microsatellite analysis on cerebral atherosclerotic plaques. Methods Twenty-seven cerebral atherosclerotic plaques were assessed for loss of heterozygosity (LOH) and microsatellite instability (MI) using 25 microsatellite markers located on chromosomes 2, 8, 9 and 17. DNA was extracted from the vessels as well as the respective blood from each patient and subjected to polymerase chain reaction. Results Our analyses revealed that specific loci on chromosomes 2, 8, 9 and 17 exhibited a significant incidence of LOH. Forty-six percent of the specimens showed loss of heterozygosity at 2p13–p21, 48% exhibited LOH at 8p12–q11.2, while allelic imbalance was detected in 47% of the cases. The LOH incidence was 39%, 31% and 27% at 17q21, 9q31–34 and 17p13, respectively. Genetic alterations were detected at a higher rate as compared to the corresponding alterations observed in plaques from other vessels. Discussion This is the first microsatellite analysis using atherosclerotic plaques obtained from cerebral vessels. Our results indicate an elevated mutational rate on specific chromosomal loci, suggesting a potential implication of these regions in atherogenesis.
An Alternative Cyclin-D1 Splice Site is Not Linked to Inflammatory Bowel Disease-Associated Neoplasia
Authors: Kanaan Ziad , Eichenberger M. Robert , Young Michael , Colliver Daniel , Crawford Nigel , Cobbs Gary A. , Hein David W. , Galandiuk Susan 
Published: March 2018

Background Inflammatory bowel diseases (IBD) encompass inflammatory disorders affecting the gastrointestinal tract, primarily ulcerative colitis (UC) and Crohn's disease (CD). The risk of developing colorectal cancer (CRC) is increased in patients with IBD. The CCND1 protein is the regulatory subunit of an enzyme that inactivates the retinoblastoma protein, a tumor suppressor protein, and promotes progression through the G1-S phase of the cell cycle. The CCND1 870G-A gene polymorphism influences susceptibility to colorectal cancer. The mutant allele of CCND1 in IBD-associated neoplasia leads to a greater frequency of alternate splicing during transcription, resulting in a more stable CCND1 protein. This creates a higher concentration of CCND1, facilitating easier passage through the G1/S checkpoint, abnormal cell cycle progression, and possibly carcinogenesis. Methods We conducted a case-control study involving 396 individuals with IBD. IBD subgroups included CD, UC, and indeterminate colitis (IC). We studied patients with sporadic colorectal cancer (n=75) and patients without gastrointestinal disease as a control group (n=93). We extracted DNA from blood and performed polymerase chain reaction followed by high-performance liquid chromatography to screen for mutations. We confirmed the polymorphism at nucleotide A870G in exon 4. For statistical analysis, we used exact analyses of two-way contingency tables. Power calculations were done and correction for multiple testing was performed by computing the false discovery rate (FDR). Results and discussion Our study had a power of 75% at a 0.05 significance level. A870G SNP allele frequency in the IBD group was 44.8%, compared to 51.6% in the control population. Only the IC group showed a significant association with CCND1 splice site after correction for multiple testing (FDR=0.042). There were no differences between the other IBD groups and controls. Conclusion We found an association between CCND1 A870G SNP and IC group only (p=0.014, FDR=0.042). However, our data do not show an association between CCND1 A870G SNP and CD-associated or UC-associated neoplasia.
Detection of Cytokeratin 19, Human Mammaglobin, and Carcinoembryonic Antigen-Positive Circulating Tumor Cells by Three-Marker Reverse Transcription-Pcr Assay and Its Relation to Clinical Outcome in Early Breast Cancer
Authors: Chen Yan , Zou Tian Ning , Wu Zhi Ping , Zhou Yong Chun , Gu Yu Lan , Liu Xin , Jin Cong Guo , Wang Xi Cai 
Published: March 2018

Aims To investigate the diagnostic, predictive, and prognostic value of the detection of circulating tumor cells (CTCs) using a three-marker (CK19, hMAM and CEA) RT-PCR assay in patients with early breast cancer. Patients and methods Peripheral blood was obtained from 50 patients with early-stage breast cancer before any systemic adjuvant therapy and analyzed for the presence of CK-19, hMAM and CEA mRNA-positive CTCs using an RT-PCR assay. The specificity of the primers used was evaluated in 20 healthy individuals, 24 patients with benign breast disease, and 30 patients with metastatic breast cancer. The detection of CTCs was correlated with clinical outcome. Results The detection rate of three-marker-positive CTCs in the blood of patients with early breast cancer was 54.0%, significantly higher than in patients with benign breast disease and healthy blood donors (p=0.002 and p=0.000, respectively). The three-marker RT-PCR assay had 58.8% sensitivity in the parallel test and 100% specificity for CTC detection in the serial test, which was higher than the sensitivity and specificity of single-marker assays. For early breast cancer, correlation analysis between detection of three-marker-positive CTCs and clinicopathological characteristics indicated that detection of three-marker-positive CTCs was significantly correlated with elevated serum CEA levels (p=0.001). After three years of follow-up, 13 of the 27 patients with three-marker-positive CTCs in their blood had relapsed and detection of three-marker-positive CTCs was significantly associated with locoregional recurrence and/or distant metastasis (p=0.002). Detection of three-marker-positive CTCs in peripheral blood was an independent risk factor for reduced median relapse-free interval (p=0.000). Conclusion The three-marker RT-PCR assay can enhance the sensitivity and specificity of CTC detection compared to single-marker assay. Detection of three-marker-positive CTCs was associated with relapse and might have important predictive and prognostic implications in early breast cancer.
Evidence that Genetic Variants of Metabolic Detoxication and Cell Cycle Control Are Not Related to Gallbladder Cancer Risk in Chilean Women
Authors: Tsuchiya Yasuo , Baez Sergio , Calvo Alfonso , Pruyas Martha , Nakamura Kazutoshi , Kiyohara Chikako , Oyama Mari , Ikegami Kikuo , Yamamoto Masaharu 
Published: March 2018

Background and aims High consumption of red chili pepper has been shown to be a risk factor for gallbladder cancer (GBC) in Chilean women. However, genetic factors in addition to this and other environmental factors may also be associated with an increased risk of GBC. We aimed to examine the associations of cytochrome P450 1A1 (CYP1A1), glutathione S-transferase class mu (GSTM1), and tumor protein p53 (TP53) polymorphisms with the risk of GBC in Chilean women. Methods A hospital-based case-control study of 57 patients with GBC, 119 patients with gallstones, and 70 controls was conducted. The statuses of the polymorphisms CYP1A1 rs4646903, CYP1A1 rs1048943, and TP53 rs1042522 were assayed using Custom Taqman® SNP Genotyping Assays and TaqMan®SNP Genotyping Assay. GSTM1 deletion polymorphism was detected by allele-specific PCR analysis. Results No significant differences in the genotypic or allelic frequencies in the CYP1A1, GSTM1, and TP53 polymorphisms were found between the three groups. Conclusion These genetic variants were not related to an increased risk of GBC in Chilean women. Other polymorphisms, such as red-chili-pepper-related polymorphisms, may contribute to the development of GBC in Chilean women.
Serum SCCA, Cyfra 21–1, EGFR and Cyclin D1 Levels in Patients with Oral Squamous Cell Carcinoma
Authors: Feng Xiao-yu , Li Jian-hua , Li Jin-zhong , Li Hua , Han Zheng-xue , Xing Ru-dong 
Published: March 2018

Objectives To determine the concentrations of SCCA, Cyfra 21–1, EGFR and Cyclin D1 in serum of patients with oral squamous cell carcinoma, and investigate their diagnostic value and their relationship with clinical stage, histological differentiation and lymph node metastasis. Methods Seventy hospitalized patients with oral squamous cell carcinoma and 72 healthy individuals were included in the study. Venous blood was collected from all study participants, in the oral carcinoma patients before tumor resection. One week after surgery, venous blood was collected again from 20 patients. Serum marker levels were determined by enzyme-linked immunosorbent assay (ELISA). Results The serum SCCA, EGFR and Cyclin D1 concentrations were significantly higher in patients with oral squamous cell carcinoma than in healthy controls, while there was no significant difference in Cyfra 21–1 levels between patients and controls. The serum SCCA concentration decreased after surgery, but there was no significant difference in the serum Cyfra 21–1, EGFR and Cyclin D1 concentrations before and after surgery. Serum SCCA, Cyfra 21–1, EGFR and Cyclin D1 concentrations were not correlated with clinical stage, histological differentiation and lymph node metastasis. When SCCA, EGFR and Cyclin D1 were measured separately, EGFR had the highest diagnostic sensitivity and accuracy and Cyclin D1 had the highest specificity; when any two of the markers were tested in combination, the combined detection of EGFR and Cyclin D1 had the highest sensitivity, specificity and accuracy. Conclusions SCCA, EGFR and Cyclin D1 may prove to be useful tumor markers in oral squamous cell carcinoma. The combined determination of EGFR and Cyclin D1 may be of value in the diagnosis of oral squamous cell carcinoma. Serum SCCA may be used as an adjunct in monitoring treatment response.
The Potential Value of CA125 as a Tumour Marker in Small Volume, Non-Evaluable Epithelial Ovarian Cancer
Authors: Cruickshank D.J. , Terry P.B. , Fullerton W.T. 
Published: March 2018

Seventy four consecutive patients with epithelial ovarian cancer have been followed up longitudinally with serial serum CA125 for up to 48 months. From this database, the CAl25 changes in small volume disease have been evaluated. For long term complete responders (n = l2), the mean plateau level of CA125 was 7.2 U/ml (95% confidence interval; 5.6 to 9.2 U/ml). The natural half-life of CA125 at 5.1 days (range 3.8 to 7 days) was calculated from five patients with Stage I and II disease who underwent complete surgical excision. A mean lead time of 99 days (range 14 to 255 days) was demonstrated between marker detection of disease progression and clinically apparent progressive disease in 12 out of 13 patients (92%) who relapsed after chemotherapy induced complete remission. The threshold of tumour volume detection with CA125 is unlikely to be determined by an arbitrary cut-off level. The kinetics of CA125 provide more useful information and the potential to define complete response or indeed cure with CA125 parameters requires further investigation.
Characterization of Monoclonal Antibody 436 Recognizing the ARG-PRO-ALA-PRO Sequence of the Polymorphic Epithelial Mucin (PEM) Protein Core in Breast Carcinoma Cells
Authors: Nuti M. , Turchi V. , Rughetti A. , Viacava P. , Masci A.M. , Castagna M. , Frati L. 
Published: March 2018

Epithelial mucins have obtained increasing clinical relevance since they were found in the serum of cancer patients and were shown to be elevated in metastatic disease. We report here the characterization of the monoclonal antibody (MAb) 436 which recognises the protein core of the polymorphic epithelial mucin (PEM) of the human breast. MAb 436 was generated by immunizing Balb/c mice with membrane-enriched fractions prepared from metastatic lesions in the axillary lymph nodes. The antigenic determinant recognized by the MAb 436 is expressed on the surface of breast cancer cells and was measured by ELISA on all of 50 cytosol preparations of primary breast tumors. Immunohistochemistry showed 98% of primary and 100% of metastatic breast cancer lesions to be positive with the 436 antigenic determinant expressed both in the cytoplasm and at the plasma membrane level of the tumor cells. Moreover, the antigen was expressed in a homogeneous fashion (80-100% of the total number of tumor cells) in more than 60% of the tumors. Reactivity with normal tissues was rare and scattered and restricted to glandular structures particularly at the luminal border level except for the distal and collecting tubules of adult and fetal kidney, where a cytoplasmic 436 antigen distribution was observed. Other cancers proved positive but the reactivity was always variable and heterogeneous. The antigen recognized by MAb 436 appears in Western Blotting as a Mr of more than 200,000 daltons protein resolved in two bands. Epitope mapping experiments using overlapping octapeptides in the repeat unit of the PEM identified in the RPAP (Arg-Pro-Ala-Pro) sequence the binding site of the 436 antigen. With the selective reactivity shown and the homogeneous expression of the corresponding epitope in breast cancer cells of primary and metastic lesions, the MAb 436 represents a good reagent with potential application in the diagnosis and therapy of breast cancer.