bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptional Inactivation of p53, Bax, Bcl-2 and Mdm2 Correlates with Malignant Transformation of the Uterine Cervix
Authors: Soufla G. , Baritaki S. , Sifakis S. , Zafiropoulos A. , Spandidos D.A.
Published: January 2018

Deregulation of the apoptotic machinery plays a major role in cell death, cellular transformation and cancer. p53, Bcl-2, Bcl-XL, Bax and Mdm2 mRNA expression patterns were evaluated in tissue samples with cervical intraepithelial neoplasia (CIN) and cervical cancer compared to those of normal cervical tissues, and correlated with the underlying cervical lesions. Transcript levels of the above genes were assessed by RT-PCR analysis in a total of 44 cervical specimens. p53, Bcl-2, Bax and Mdm2 transcript levels were significantly different in the normal, CIN and cancer specimen groups (p=0.003, p=0.009, p=0.040 and p=0.001, respectively). Specifically, p53, Bax and Bcl-2 exhibited substantially lower transcript levels in CIN lesions compared to controls, whereas Bax mRNA levels showed a significant decrease in cancer compared to normal specimens. Mdm2 mRNA expression was considerably lower in cancer than in CIN lesions or normal cervix. High-grade squamous intraepithelial lesions exhibited lower p53 and Bcl-2 mRNA levels than controls (p=0.002, p=0.016). Coexpression analysis revealed more correlations between the above apoptosis-related molecules in normal tissues compared to CIN or cancer specimens. p53 showed significant coexpression with Bax, Bcl-2 and Mdm2 (p=0.040, p=0.013 and p=0.015, respectively) in normal cervical specimens. Bax and Bcl-XL mRNA expression was negatively correlated. Mdm2 transcriptional levels correlated significantly with those of Bax, Bcl-XL and Bcl-2. Our findings show that p53, Bax, Bcl-2 and Mdm2 mRNA expression levels correlate with the malignant transformation of the uterine cervix. mRNA coexpression patterns of the members of the pro- and anti-apoptotic family examined in cervical carcinogenesis were found to be disrupted in CIN and cancer, as already demonstrated at the protein level.
A New Nested Primer Pair Improves the Specificity of Ck-19 Mrna Detection by Rt-Pcr in Occult Breast Cancer Cells
Authors: Balducci E. , Azzarello G. , Valori L. , Toffolatti L. , Bolgan L. , Valenti M.T. , Bari M. , Pappagallo G.L. , Ausoni S. , Vinante O.
Published: January 2018

Reverse transcription polymerase chain reaction (RT-PCR) of cytokeratin-19 (CK-19) has been widely used to detect small numbers of circulating malignant epithelial cells in the bone marrow or the peripheral blood of patients with breast cancer. However, a high percentage of false positive results has been recorded and conflicting reports question the clinical relevance of this technical approach. We demonstrate that the use of a new nested primer pair for CK-19 RT-PCR avoids false positive results without affecting the sensitivity of the assay. Our experiments were carried out using MCF-7 cells alone or mixed with peripheral blood mononuclear cells (PBMNC) of healthy donors. The results were also validated in a large series of healthy donors and in a preliminary study on a limited number of patients with breast cancer, thus suggesting that our assay is feasible for application in the clinical evaluation of occult malignant epithelial cells.
Preoperative Plasma Soluble Urokinase Plasminogen Activator Receptor as a Prognostic Marker in Rectal Cancer Patients. An Eortc-Receptor and Biomarker Group Collaboration
Authors: Riisbro R. , Christensen I.J. , Nielsen H.J. , Brünner N. , Nilbert M. , Fernebro E.
Published: January 2018

Background and aims

Since approximately 30% of patients with Dukes’ stage B colorectal cancer will experience disease recurrence within five years of primary treatment, current staging of patients with early colorectal cancer apparently fails to adequately predict patient outcome. It has previously been shown that the preoperative plasma concentration of soluble urokinase plasminogen activator receptor (suPAR) is associated with the survival of patients with early colorectal cancer. In this study we sought to confirm the independent prognostic value of suPAR in rectal cancer.

Methods

suPAR was retrospectively determined by two different versions of a suPAR ELISA in preoperatively collected plasma samples from a Swedish (n=354) and a Danish (n=255) cohort of rectal cancer patients.

Results

In both cohorts the suPAR concentration was significantly higher in Dukes’ stage D patients than in Dukes’ stage A-C patients (p<0.0001). Among Dukes’ stage A-C patients, no differences in median suPAR values were seen. In univariate analysis, continuous suPAR was found to be associated with survival (p<0.0001 in both cohorts). Of particular interest was that similar results were obtained for Dukes’ stage A and B patients when analyzed separately. In multivariate analysis, continuous suPAR was found in both cohorts to be independent of Dukes’ stage.

Conclusions

This study confirms that the preoperative concentration of plasma suPAR contains independent prognostic information on patients with rectal cancer. This result was independent of the two different versions of an in-house suPAR ELISA used to perform the analyses. The next step in the evaluation of suPAR as a prognostic parameter in rectal cancer will be to launch an appropriately dimensioned prospective study where the benefit of applying preoperative plasma suPAR measurement to clinical decision-making regarding adjuvant therapy is assessed.
Free DNA in Urine: A New Marker for Bladder Cancer? Preliminary Data
Authors: Zancan M. , Franceschini R. , Mimmo C. , Vianello M. , Di Tonno F. , Mazzariol C. , Malossini G. , Gion M.
Published: January 2018

The aim of the present preliminary study was to investigate the presence of free DNA (FDNA) in urine as a possible marker for the diagnosis of bladder cancer. Naturally voided morning urine specimens were collected from 57 patients with suspected bladder cancer before cystoscopy. A standard urine test was performed; the specimens were then processed in order to obtain a quantitative evaluation of the presence of free DNA in the urine. Twenty-two patients were excluded from the study because they had leukocyturia and/or bacteriuria. Free DNA concentrations higher than 250 ng/mL were found in all 16 patients showing bladder cancer at cystoscopy and in seven (36.8%) of the 19 patients with negative cystoscopy. Urinary FDNA seems to have an excellent sensitivity: we observed no false negative cases and 36.8% false positive cases. By contrast, only 6.25% of the bladder cancer patients had positive urine cytology. Our results seem promising, although further studies and larger numbers are needed to define urinary free DNA as a reliable marker of bladder cancer.
An Epidermal Growth Factor Receptor Intron 1 Polymorphism in Healthy Women in Poland
Authors: Bielawski K.P. , Klos P. , Welnicka-Jaskiewicz M. , Tidow N. , Brandt B. , Falkiewicz B. , Zaczek A.
Published: January 2018

The frequency of CA allele combinations was assessed in healthy women from Poland and compared to previously published polymorphism data of individuals from Germany and a Caucasian reference group. There were close similarities between these three geographically and ethnically similar populations. By contrast, the distribution of these alleles in European and Asian (Japan) populations proved to be different. There might therefore be major ethnic differences in allelic frequencies of EGFR intron 1 polymorphism. Our results provide new data on EGFR microsatellite instability and may contribute to the understanding of EGFR gene expression regulation. The clinical relevance of these findings warrants further evaluation.
The Differential Regulation of Human Telomerase Reverse Transcriptase and Vascular Endothelial Growth Factor May Contribute to the Clinically More Aggressive Behavior of P63-Positive Breast Carcinomas
Authors: Ribeiro-Silva A. , Becker de Moura H. , Ribeiro do Vale F. , Zucoloto S.
Published: January 2018

p63, a p53 homologue, is a myoepithelial cell marker in the normal mammary gland but p63-positive neoplastic cells may be found in up to 11% of invasive breast carcinomas. This study aims to verify the relationship between p63 expression and several clinicopathological features and tumor markers of clinical significance in breast pathology including key regulators of the cell cycle, oncogenes, apoptosis-related proteins, metalloproteinases and their inhibitors. Immunohistochemistry with 27 primary antibodies was performed in 100 formalin-fixed paraffin-embedded samples of invasive ductal carcinomas. p63-positive cells were found in 16% of carcinomas. p63-positive carcinomas were poorly differentiated, hormone receptor-negative neoplasms with a high proliferation rate. p63 also correlated with advanced pathological stage, tumor size, and the expression of human telomerase reverse transcriptase (hTERT), tissue inhibitor of matrix metalloproteinase 1 (TIMP1) and vascular endothelial growth factor (VEGF). The expression of TIMP1 suggests that the anti-proteolytic stimuli may be preponderant in p63-positive carcinomas. hTERT activity is associated with nodal metastases and cellular proliferation. VEGF regulates angiogenesis, which is also a fundamental event in the process of tumor growth and metastatic dissemination. Thus, the differential regulation of hTERT and VEGF in p63-positive breast carcinomas may contribute to the clinically more aggressive behavior of these neoplasms.
Pancreatic Cancer Cells Invasiveness is Mainly Affected by Interleukin-1β not by Transforming Growth Factor-β1
Authors: Greco E. , Basso D. , Fogar P. , Mazza S. , Navaglia F. , Zambon C.-F. , Falda A. , Pedrazzoli S. , Ancona E. , Plebani M.
Published: January 2018

Background

We investigated in vitro whether IL-1β and TGF-β1 affect pancreatic cancer cell growth, adhesion to the extracellular matrix and Matrigel invasion.

Materials and methods

Adhesion to fibronectin, laminin and type I collagen, and Matrigel invasion after stimulation with saline, IL-1β and TGF-β1 were evaluated using three primary and three metastatic pancreatic cancer cell lines.

Results

Extracellular matrix adhesion of control cells varied independently of the metastatic characteristics of the studied cell lines, whereas Matrigel invasion of control cells was partly correlated with the in vivo metastatic potential. IL-1β did not influence extracellular matrix adhesion, whereas it significantly enhanced the invasiveness of three of the six cell lines. TGF-β1 affected the adhesion of one cell line, and exerted contrasting effects on Matrigel invasion of different cell lines.

Conclusions

IL-1β enhances the invasive capacity of pancreatic cancer cells, whereas TGF-β1 has paradoxical effects on pancreatic cancer cells; this makes it difficult to interfere with TGF-β1 signaling in pancreatic cancer treatment.
Extreme Elevation of Serum Alpha Fetoprotein in Decompensated Cirrhosis without Hcc: an Ominous Sign
Authors: Senturk H. , Cumali R.
Published: January 2018

Three cases of extreme elevation of serum alpha fetoprotein (>10,000 ng/mL) with decompensated cirrhosis without demonstrable hepatocellular carcinoma are reported. While 2 patients died of liver failure, 1 survived after liver transplantation. Extreme elevation of alpha fetoprotein not associated with hepatocellular carcinoma in liver cirrhosis heralds an ominous prognosis necessitating urgent liver transplantation.
Investigation of Tissue Inhibitor of Metalloproteinases 1 in Plasma from Colorectal Cancer Patients and Blood Donors by Surface-Enhanced Laser Desorption/Ionization Time-of-Flight Mass Spectrometry
Authors: Caspersen M.B. , Sørensen N.M. , Schrohl A.S. , Iversen P. , Nielsen H.J. , Brünner N.
Published: January 2018

Early detection of colorectal cancer (CRC) improves patient survival. Plasma tissue inhibitor of metalloproteinases 1 (TIMP-1) measurements by enzyme-linked immunosorbent assay (ELISA) have been suggested as a new method for the early detection of CRC. To further investigate the nature of TIMP-1 in plasma, surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI TOF MS) was used. TIMP-1 measurements of plasma from 16 healthy donors and 14 CRC patients were performed using TIMP-1 monoclonal antibody in SELDI TOF MS and ELISA. SELDI TOF MS applying an antibody to TIMP-1 revealed that human plasma TIMP-1 has a mass of 25.1 kDa and exhibits several isoforms. Both methods showed increased plasma TIMP-1 values for cancer patients as compared to healthy individuals. The p values for the separation of the groups were 0.0019 for ELISA and <0.0001 for SELDI TOF MS. CRC did not fundamentally affect the appearance of TIMP-1 as evaluated by SELDI TOF MS.
β-CTX and ICTP Act as Indicators of Skeletal Metastasis Status in Male Patients with Non-Small Cell Lung Cancer
Authors: Kong Q.Q. , Sun T.W. , Dou Q.Y. , Li F. , Tang Q. , Pei F.X. , Tu C.Q. , Chen Z.Q.
Published: January 2018

Bone metastasis is common in lung cancer patients and associated with reduced quality of life and reduced overall and median survival, so the early detection of bone metastasis and monitoring of its status is very important for clinicians. Serum bone-specific alkaline phosphatase (BAP), osteocalcin (OC), β isomer of C-terminal telopeptide of type I collagen (β-CTX) and cross-linked C-terminal telopeptide of type I collagen (ICTP) were compared with regard to their usefulness as indicators of bone metastasis in lung cancer. The serum concentrations of the 4 markers were measured by commercially available tests in 96 male patients with non-small cell lung cancer and 30 male patients with other pulmonary diseases. The levels of both β-CTX and ICTP were significantly higher in 61 lung cancer patients with bone metastases than in 35 lung cancer patients without bone metastases (both p<0.001), and significantly correlated with the extent of bone disease. Although ICTP had a better sensitivity and accuracy than β-CTX (75.4% vs 65.6% and 72.9% vs 68.8%, respectively), they had a similar area under the receiver operating characteristic curve (0.85 vs 0.83). These results support the use of β-CTX and ICTP as an adjunct tool for the diagnosis and screening of bone metastasis in lung cancer.
High-Risk Human Papillomavirus (HPV) in Parotid Lesions
Authors: Vageli D. , Sourvinos G. , Ioannou M. , Koukoulis G.K. , Spandidos D.A.
Published: January 2018

Although several studies have reported that oropharyngeal infection with HPV may predispose to tumorigenesis, little is known about the etiological factors of salivary gland tumors and the presence of HPV We studied 9 parotid lesions for HPV infection including an oncocytoma, an acinic cell carcinoma, a high-grade adenocarcinoma, a low-grade polymorphous adenocarcinoma, a Warthin's tumor and 2 pleomorphic adenomas, a lymphoepithelial cyst and a lipoma of the parotid gland. DNA was extracted from formalin-fixed and paraffin-embedded tissue sections. Solution PCR for HPV detection was performed using the GP5+/GP6+ primers, while HPV typing was carried out by multiplex PCR for HPV6, 11, 16, 18, and 33; positive samples were recorfirmed by PCR with specific primers for each type. Quantitative real-time PCR for the high-risk HPV genotypes 16, 18, 31, 33, 35, 52, 58 and 67 was also performed to quantitate the viral load. Finally, in situ PCR was employed with HPV16-specific primers by direct-detection method. Seven of the 9 parotid lesions were HPV positive while 6 of these 7 had been infected by HPV16 and/or HPV18 oncogenic types. High viral load of high-risk genotypes of HPV was found in the oncocytoma, in one of the pleomorphic adenomas, and in the Warthin's tumor. Finally, in situ PCR indicated that HPV16 amplification occurred in the salivary gland tumors. This is the first time that high-risk HPV genotypes are detected in these histological types of parotid lesions, suggesting the possible involvement of the virus in the disease.
Matrix Metalloproteinase-19 is a Predictive Marker for Tumor Invasiveness in Patients with Oropharyngeal Squamous Cell Carcinoma
Authors: Velinov N. , Aebersold D. , Haeni N. , Hlushchuk R. , Weinstein F. , Sedlacek R. , Djonov V.
Published: January 2018

Aims

To evaluate the expression of matrix metalloproteinase-19 (MMP-19) in oropharyngeal squamous cell carcinoma along with its association with structural features of invasiveness. To investigate whether MMP-19 expression correlates with lymphatic or systemic metastasis and prognosis in patients who have received definitive radiotherapy.

Methods and results

The histological evaluation of the invasive front was based on Bryne's malignancy grading system. We correlated the immunohistochemical expression pattern with morphological parameters which characterize tumor invasiveness such as keratinization, nuclear polymorphism, invasion pattern, and the host inflammatory response. Local immunoreactivity for MMP-19 was positively correlated with tumor invasiveness as reflected in its structural characteristics and the degree of nuclear polymorphism, and negatively correlated with the inflammatory response of the host. No correlation existed between MMP-19 expression and clinicopathological features (TNM stage, grade of differentiation) or a patient's outcome and prognosis.

Conclusions

This latter finding probably reflects the unique change for MMPs from high immunoreactivity within healthy tissue areas and non-invasive tumor parts, through absence in the least invasive neoplastic regions, to strong re-expression at a highly invasive front of the same tumor. Our findings indicate that MMP-19 can be used as a marker for tumor invasiveness in patients with oropharyngeal squamous cell carcinoma.
Altered Salivary Profile in Heavy Smokers and its Possible Connection to Oral Cancer
Authors: Nagler R.M.
Published: January 2018

Saliva is the first biological fluid to encounter inhaled cigarette smoke, whose numerous carcinogens and oxidants are responsible for the oral cancer so prevalent among smokers. Whole saliva, collected from 25 consenting heavy smokers and from a control group of 25 age- and gender-matched non-smokers, was subjected to sialochemical, biochemical, immunological and oxidative analyses. The mean flow rate was significantly higher in smokers than in non-smokers, as were the median activity value of superoxide dismutase (SOD) and the total salivary antioxidant capacity (ImAnOx) (by 32% and 12%, respectively, p=0.05). The salivary carbonyl concentration (an oxidative stress indicator) was significantly higher by 126% (p=0.0006) among smokers, while lactate dehydrogenase, albumin, total immunoglobulin G, and the metalloproteinases MMP-2 and MMP-9 concentrations were significantly lower in the smokers, by 86% (p=0.003), 65% (p=0.003), 61% (p=0.048), 35% (p=0.005) and 55% (p=0.035), respectively. Apparently, the oral cavity's salivary antioxidant system fails to cope with the severe attack of reactive oxygen species originating in cigarette smoke. Moreover, various other salivary functional and protective parameters also decreased among the smokers. Hence, further research aimed at examining the possibility of administration of agents as antioxidants or saliva substitutes to the oral cavity of smokers should be considered.
Measurement of mRNA of 11 Biomarkers by RT-PCR to Detect Lymph Node Involvement in Cervical Cancer
Authors: Samouëlian V. , Revillion F. , Alloy N. , Lhotellier V. , Leblanc E. , Peyrat J.P.
Published: January 2018

Lymph node metastases are a major prognostic factor in cervical carcinomas. The aim of this study was to characterize the expression of 11 markers in cervical tumors and negative lymph nodes and to determine which ones could be helpful for improving the specificity of molecular diagnosis of nodal involvement. Using TaqMan RT-PCR, we studied the expression of CK19, MUC1, HER1–HER4, VEGF, VEGF-C, uPA, MMP9, and PRAD1 in uterine cervical tumors and in histologically nonmetastatic lymph nodes of 8 patients diagnosed with locally advanced cervical cancer. We observed that CK19, MUC1, HER1–HER3, uPA, and VEGF had a significantly higher expression in cervical tumors than in the negative nodes, whereas VEGF-C expression level was higher in the negative nodes than in the tumors. PRAD1 harbored similar expression levels in the tumors and in the negative nodes. Interestingly, 1 of the 4 patients who presented a clinical recurrence, showed elevated HER1, HER2, uPA, and VEGF in the histologically negative nodes. Our results suggest that CK19, MUC1, HER1–3, uPA, and VEGF are biomarkers that have a higher expression in tumoral cervical tissues compared with the negative lymph nodes and could be useful to diagnose nodal involvement in uterine cervical carcinoma. Our results should encourage us in continue to investigate a greater number of patients, including patients with histologically involved nodes.
Expression of Mina53 and its Significance in Gastric Carcinoma
Authors: Zhang Q. , Hu CM. , Yuan Y.S. , He C.H. , Zhao Q. , Liu N.Z.
Published: January 2018

Aim

To study the expression of Mina53 and its relationships with clinicopathological characteristics, antioncogene inactivation and tumor proliferation in human gastric carcinoma, and to explore the role of Mina53 in carcinogenesis and tumor progression.

Methods

Expression of Mina53 and proliferating cell nuclear antigen (PCNA) was determined in gastric carcinoma (n=79), gastric dysplasia (n=21) and normal gastric tissues (n=20), while p53 was measured in gastric carcinoma tissues by immunohistochemistry.

Results

Mina53 was negatively expressed in all normal mucosa tissues. Dysplasia specimens showed weakly positive staining for Mina53 in 3 of 21 cases. Elevated expression of Mina53 was observed in 72 (91.1%) of the gastric carcinomas. No significant associations were found between Mina53 and clinicopathological characteristics such as sex, age, histological differentiation, distant metastasis and lymph node metastasis (p>0.05). There was a significant association with depth of invasion (χ2=5.385, p<0.05) and TMN stage (χ2=6.255, p<0.05). In gastric carcinoma, positive staining for p53 was detected in 53 of 79 cases (67.1%), showing a significant association with Mina53 (χ2=5.161, p<0.05). The mean (± SD) PCNA labeling index for gastric carcinoma was 39.47±16.92%. Mina53 expression was positively associated with PCNA level (r=0.756, p<0.01).

Conclusion

Mina53 was overexpressed in gastric carcinoma and associated with tumor proliferation and antioncogene inactivation. Mina53 could therefore play an important role in the carcinogenesis and progression of gastric carcinoma.
Protein Biochip Array of Adhesion Molecule Expression in Peripheral Blood of Patients with Nasal Polyposis
Authors: Corsi M.M. , Pagani D. , Dogliotti G. , Perona F. , Sambataro G. , Pignataro L.
Published: January 2018

Nasal polyposis is a chronic non-infectious inflammatory disease of the nasal and paranasal cavity mucosa of unknown multifactorial origin in which inflammatory cells, and in particular eosinophils, seem to play a pivotal role. Eosinophil migration from the bloodstream to nasal polyps is considered to be specific and is a complex process involving several different molecules such as ICAM-1, VCAM-1, and L-, P- and E-selectins. The aim of this study was to investigate, using a protein biochip array technology, the concentrations of these molecules in the peripheral blood of a group of patients affected by nasal polyposis. Patients exhibited a significantly higher expression of VCAM-1, E-selectin, and L-selectin compared to healthy controls, and Spearman's rank correlation test limited to the molecules with significant between-group differences demonstrated a significant correlation between VCAM-1 and E-selectin, VCAM-1 and L-selectin, and E-selectin and L-selectin. The results of this investigation are in line with those coming from various imunohistochemical analyses, and seem to confirm the role of inflammation in the pathogenesis of nasal polyposis. These molecules may also represent novel therapeutic targets in the treatment of nasal polyps, and may allow the selection of pharmacological prophylactics that would allow effective inhibition of the inflammation induced by a given allergen.
PSA Doubling Time as a Predictor of the Outcome of Random Prostate Biopsies Prompted by Isolated PSA Elevation in Subjects Referred to an Outpatient Biopsy Facility in a Routine Clinical Scenario
Authors: Ciatto S. , Rubeca T. , Martinelli F. , Pontenani G. , Lombardi C. , Di Lollo S.
Published: January 2018

Aim

To assess the validity of PSA doubling time (PSADT) as a predictor of prostate sextant biopsy outcome in patients with PSA levels in the 4–10 ng/mL range.

Material and methods

A consecutive series of 355 sextant biopsies performed during 2001–2007 in subjects with negative digital rectal examination and transrectal ultrasonography was considered. Variables tested as possible predictors were age, total and free/total PSA value, PSA velocity and PSA doubling time. While PSA at time of biopsy and free/total PSA were determined with a standardized method undergoing strict quality control, previous PSA values used to assess velocity/doubling time came from other labs using different assays over widely varying intervals of time. The association with biopsy outcome (cancer vs non-cancer) was investigated by univariate and multivariate analysis.

Results

Apart from free/total PSA ratio, no other studied variable showed a statistically significant and independent association with biopsy outcome, either at univariate or multivariate analysis. No studied variable had a good performance as a biopsy indicator. Depending on the variable considered, 1.17 to 1.97 cancers would be missed to spare 10 benign biopsies.

Conclusion

When based on PSA data determined with different assays over widely varying intervals and in the absence of an underlying protocol for PSA surveillance, PSA velocity and doubling time should never discount a biopsy prompted by total PSA elevation.
A Prediction Model for Breast Cancer Recurrence after Adjuvant Hormone Therapy
Authors: Boracchi P. , Coradini D. , Antolini L. , Oriana S. , Dittadi R. , Gion M. , Daidone M.G. , Biganzoli E.
Published: January 2018

Hormone therapy with tamoxifen has long been the established adjuvant treatment for node-positive, estrogen–receptor-positive breast cancer in postmenopausal women. Since 30–40% of these patients fail to respond, reliable outcome prediction is necessary for successful treatment allocation. Using pathobiological variables (available in most clinical records: tumor size, nodal involvement, estrogen and progesterone receptor content) from 596 patients recruited at a comprehensive cancer center, we developed a prediction model which we validated in an independent cohort of 175 patients recruited at a general hospital. Calculated at 3 and 4 years of follow-up, the discrimination indices were 0.716 [confidence limits (CL) 0.641, 0.752] and 0.714 (CL 0.650, 0.750) for the training data, and 0.726 (CL 0.591, 0.769) and 0.677 (CL 0.580, 0.745) for the testing data. Waiting for more effective approaches from genomic and proteomic studies, a model based on consolidated pathobiological variables routinely assessed at relatively low costs may be considered as the reference for assessing the gain of new markers over traditional ones, thus substantially improving the conventional use of prognostic criteria.
Heat Shock Protein Expression Independently Predicts Survival Outcome in Schistosomiasis-Associated Urinary Bladder Cancer
Authors: El-Kenawy A. EL-Meghawry , El-kott A.F. , Hasan M.S.
Published: January 2018

Background

Heat shock proteins (HSPs) are synthesized by cells in response to various stress conditions, including carcinogenesis. These molecules have been studied in several malignancies, among which bladder carcinoma. This is the first study attempting to clarify the significance of HSP27 and HSP70 in schistosomiasis-associated bladder carcinoma and their relation to prognosis.

Methods

HSP27 and HSP70 were localized immunohistochemically in tissue sections from 75 schistosomiasis-associated bladder carcinomas. Their expression was correlated with clinical and pathological features and their impact on 5-year disease-free survival was studied with univariate and multivariate analysis.

Results

I N all, 45 and 51 patients were positive for HSP27 and HSP70 expression, respectively. A significant correlation was found between expression of both HSPs and tumor grade, stage, DNA ploidy and recurrence. In univariate analysis, a statistically significant association of HSP27 and HSP70 expression with 5-year disease-free survival was found. In a multivariate Cox proportional hazards model, both HSP27 and HSP70 maintained a statistically significant impact on survival.

Conclusions

The current results indicate that expression of HSP27 and HSP70 may have prognostic relevance in patients with schistosomiasis-associated bladder cancer. HSPs may be useful markers for patients with this type of bladder carcinoma and may be used for predicting disease progression.
Expression of Heterochromatin Protein 1 in the Primary Tumor of Breast Cancer Patients in the Presence or Absence of Occult Metastatic Cells in the Bone Marrow
Authors: Abreu A.P.S. , Milani C. , Katayama M.L.H. , Barbosa E.M. , da Fonseca L. Gomes , Góes J.CS. , Brentani M.M. , Folgueira M.A.A. Koike
Published: January 2018

Gene silencing may occur in breast cancer samples from patients presenting with occult metastatic cells in the bone marrow and one mechanism regulating gene suppression is heterochromatin formation. We have studied whether members of the heterochromatin protein 1 family (HP1Hsα, HP1Hsβ and HP1Hsγ), which take part in chromatin packaging and gene expression regulation, were differentially expressed in tumors from patients with and without occult metastatic cells in their bone marrow. Tumor samples and bone marrow aspirates were obtained from 37 breast cancer patients. Median age was 63 years and 68% of the patients presented with clinical stage I/II disease. Presence of occult metastatic cells in bone marrow was detected through keratin-19 expression by nested RT-PCR in samples from 20 patients (54.1%). The presence of occult metastatic cells in bone marrow was not associated with node involvement, histological grade, estrogen receptor and ERBB2 immunoexpression. Relative gene expression of HP1Hsα, HP1Hsβ and HP1Hsγ was determined by real-time RT-PCR and did not vary according to the presence of occult metastatic cells in bone marrow. In addition, the combined expression of these three transcripts could not be used to classify samples according to the presence of bone marrow micrometastasis. Our work indicates that regulation of heterochromatin formation through HP1 family members may not be the sole mechanism implicated in the metastatic process to the bone marrow.
Detection of Cytokeratin 19 mRNA and CYFRA 21–1 (Cytokeratin 19 Fragments) in Blood of Tunisian Women with Breast Cancer
Authors: Marrakchi R. , Ouerhani S. , Benammar S. , Rouissi K. , Bouhaha R. , Bougatef K. , Messai Y. , Khadimallah I. , Rahal K. , Ammar-Elgaaied A. Ben
Published: January 2018

Cytokeratin 19 (CK19) is an acidic protein of 40 kDa that is part of the cytoskeleton of epithelial cells. It is highly expressed by all epithelial cells and represents a useful indicator of epithelial differentiation. The soluble fragment of CK19 (CYFRA 21–1) can be a useful circulating tumor marker and can be detected in the serum of cancer patients. The development of metastasis in patients with cancer of epithelial origin is due to the migration of tumor cells from the original tumor to distant organs. In order to detect micrometastasis in patients with breast cancer, we evaluated and compared CK19 gene expression using RT-PCR in blood samples collected from 80 healthy women and 80 patients with localized or metastatic breast cancer. The concentration of the soluble CK19 fragment CYFRA 21–1 was measured in serum of all study subjects by radioimmunoassay employing specific monoclonal antibodies. The relationship between the expression of this molecular marker and clinical stage, tumor differentiation and CK19 mRNA transcripts was investigated. We found that CK19 mRNA expression in blood (as a direct index of the presence of circulating tumor cells) was not correlated with CYFRA 21–1.
CHFR Promoter Hypermethylation and Reduced CHFR mRNA Expression in Ovarian Cancer
Authors: Gao Ying , Lou Ge , Zhang Guang-Mei , Sun Xi-Wen , Ma Yu-Yan , Yang Yan-Mei , Liu Ge
Published: January 2018

Background

Ovarian cancer is one of the most common cancers and can be treated with microtubule-targeting drugs. Checkpoint with forkhead and ring finger domains (CHFR) is a protein implicated in cancer sensitivity to microtubule-targeting drugs. Whereas CHFR downregulation, often with CHFR promoter hypermethylation, has been identified in a large number of tumor types, it has not been in ovarian cancer. We therefore searched for CHFR downregulation in primary ovarian tumors.

Methods

Fresh ovarian cancer tissues from 53 patients (test) and normal ovarian tissues from 21 patients (control) were tested for CHFR promoter hypermethylation and CHFR mRNA levels.

Results

The CHFR promoter was hypermethylated in 20.75% (11/53) of the ovarian cancers and none (0/21) of the normal controls. The normal controls had a mean mRNA level of 1.89 relative fluorescence units (RFU) with a range of 0.04–24.78 RFU. The cancer tissues had a mean mRNA level of 0.77 RFU with a range of 0.00–68.75 RFU. The median value of the cancer group was significantly lower than that of the control group (p=0.0067). Those cancer samples that had hypermethylated CHFR promoters also had low (n=3) or undetectable (n=8) CHFR mRNA levels.

Conclusions

In contrast to previous reports, we found that alterations in CHFR mRNA and CHFR methylation can be frequently found in ovarian cancers. CHFR hypermethylation was strongly associated with the loss of CHFR mRNA expression. CHFR downregulation in ovarian tumors may be clinically relevant as a staging biomarker, as an indicator of sensitivity to microtubule-targeting drugs, and as a future drug target.
Quantitation of the Cancer Marker LASA Using Immobilized Enzymes in a Semiautomated System
Authors: Yasinzai Masoom
Published: January 2018

Cancer patients are found to have elevated serum levels of lipid-associated sialic acid (LASA). LASA measurement provides a valuable test for the diagnosis of human cancer. The currently used measurement methods are tedious and nonselective. Here we report a method based on immobilized enzyme minicolumns in a flow system for the analysis of this clinically important analyte. Three enzymes comprising two minicolumns are introduced online and the analyte in a precisely injected volume of 20 μL is made to pass through these immobilized enzyme columns. The final product of the reaction is detected amperometrically. Neuraminidase and NANA-aldolase are coimmobilized on controlled pore glass, followed by a column of pyruvate oxidase. The method was applied to the quantitation of LASA in the sera of normal individuals and patients with cancer of the esophagus. We observed no loss of activity of the immobilized enzymes after analyzing about 300 samples. The sample throughput was 30 samples per hour.
Osteopontin is not a Specific Marker in Malignant Pleural Mesothelioma
Authors: Paleari Laura , Rotolo Nicola , Imperatori Andrea , Puzone Roberto , Sessa Fausto , Franzi Francesca , Meacci Elisa , Camplese Pierpaolo , Cesario Alfredo , Paganuzzi Michela
Published: January 2018

Background and aims: Osteopontin (OPN) is an integrin-binding protein recently shown to be related to tumorigenesis, progression and metastasis in different experimental models of malignancy. Malignant pleural mesothelioma (MPM) is a fatal disease in which the prognosis remains very poor and the knowledge of predictive factors for outcome is insufficient. The identification of new molecules involved in cancer initiation and development is a fundamental step for improving the curability of this kind of tumor. The purpose of this study is to define the role of OPN in the diagnosis of MPM by determining its prognostic and diagnostic value. Methods: a group of 24 surgically staged MPM subjects was compared with a group of 31 subjects with non-malignant pulmonary diseases, and with 37 healthy controls. Tumor tissue was analyzed for OPN by immunohistochemical tests, and plasma OPN levels were measured by an enzyme-linked immunosorbent assay. Results: Plasma OPN levels were not significantly higher in either of the patient groups compared with the control group. Immunohistochemical analysis revealed OPN staining of tumor cells in 21 of 24 MPMs. Receiver operating characteristic curve/area under the curve (ROC/AUC) analysis comparing the plasma OPN levels in the healthy group with those of MPM patients showed 40% sensitivity and 100% specificity at a cutoff value of 60.8 ng of OPN per milliliter (AUC 0.6). Conclusion: Plasma OPN levels do not discriminate between chronic inflammatory and malignant lung diseases and staining intensity in MPM specimens does not correlate with OPN plasma levels.
Methodology for the navigation optimization of a terrain-adaptive unmanned ground vehicle
Authors: Abad Eduardo Corral , Alonso Jesús Meneses , García María Jesús Gómez , García-Prada Juan Carlos
Published: January 2018

The goal of this article is to design a navigation algorithm to improve the capabilities of an all-terrain unmanned ground vehicle by optimizing its configuration (the angles between its legs and its body) for a given track profile function. The track profile function can be defined either by numerical equations or by points. The angles between the body and the legs can be varied in order to improve the adaptation to the ground profiles. A new dynamic model of an all-terrain vehicle for unstructured environments has been presented. The model is based on a half-vehicle and a quasi-static approach and relates the dynamic variables of interest for navigation with the topology of the mechanism. The algorithm has been created using a simple equation system. This is an advantage over other algorithms with more complex equations which need more time to be calculated. Additionally, it is possible to optimize to any ground-track-profile of any terrain. In order to prove the soundness of the algorithm developed, some results of different applications have been presented.
Chronic kidney disease
Authors: Ware Thuvaraka
Published: January 2018

Chronic kidney disease (CKD) is a broad term used to describe any abnormality of kidney structure or function. It is often asymptomatic in the early stages and co-exists with other chronic illnesses, such as diabetes and hypertension. It is associated with an increased risk of cardiovascular disease, end-stage renal failure, anaemia and metabolic bone disease. Early detection of CKD and managing risk factors may provide an opportunity to prevent progression of associated risks. This article will discuss the diagnosis, classification, management and complications of CKD, and when to refer to secondary care.
Genetic Diversity of Tropical Bats and Its Relationship With Ecological Role in a Tropical Semievergreen Rain Forest in El Ocote Biosphere Reserve, Chiapas, Mexico
Authors: Cruz-Salazar Bárbara , Ruiz-Montoya Lorena , Mendoza-Sáenz Víctor Hugo , Riechers-Pérez Alejandra , García-Bautista Maricela
Published: January 2018

Species that are functionally equivalent but with little taxonomical relationship may display similar genetic patterns if the ecological function evolves genetically in the same way. This study investigated the levels of genetic diversity in the D-Loop gene of random samples collected from 21 bat species inhabiting El Ocote Biosphere Reserve (REBISO, for its acronym in Spanish), and whether the genetic diversity pattern could be associated with the ecological role. Genetic differences between functional groups, localities, and species were evaluated through generalized linear models using the Gaussian distribution error family for nucleotide diversity (π) and the Poisson family for haplotype diversity ( h) and segregating sites ( s). To study the clustering pattern of species based on nucleotide variation, genetic distances (Kimura’s two-parameter model) between functional groups were calculated, and a Principal Components Analysis on genetic diversity parameters was run. Most of the species analyzed (20) maintained genetic diversity levels ranging from medium to high in all genetic diversity estimators. According to genetic distances, the species with the same ecological function shared a greater number of nucleotide substitutions, with some exceptions. The Principal Components Analysis did not detect any genetic structure in relation to the ecological function. Our study found no association between the diversity of the D-Loop gene and ecological function; nonetheless, it confirms the importance of REBISO as a reservoir of bat species richness and genetic diversity in Mexico.
Risk factors associated with liver steatosis and fibrosis in chronic hepatitis B patient with component of metabolic syndrome
Authors: Cai Shaohang , Ou Zejin , Liu Duan , Liu Lili , Liu Ying , Wu Xiaolu , Yu Tao , Peng Jie
Published: January 2018

Background

We investigated whether metabolic syndrome exacerbated the risk of liver fibrosis among chronic hepatitis B patients and risk factors associated with liver steatosis and fibrosis in chronic hepatitis B patients with components of metabolic syndrome.

Methods

This study included 1236 chronic hepatitis B patients with at least one component of metabolic syndrome. The controlled attenuation parameter and liver stiffness, patient information and relevant laboratory data were recorded.

Results

Controlled attenuation parameter was increased progressively with the number of metabolic syndrome components (p < 0.001). Multivariate analysis indicated younger age, high gamma‐glutamyltransferase level, high waist‐hip ratio, and high body mass index were independent risk factors associated with nonalcoholic fatty liver disease among chronic hepatitis B patients with metabolic syndrome. In the fibrosis and non‐fibrosis groups, most of blood lipid was relatively lower in fibrosis group. An increased proportion of chronic hepatitis B patients with liver fibrosis was found concomitant with an increasing number of components of metabolic syndrome. Male gender, older age, smoking, aspartate aminotransferase levels, high body mass index, and low platelet level were identified as independent risk factors associated with liver fibrosis.

Conclusions

For chronic hepatitis B patients with coexisting components of metabolic syndrome, stratification by independent risk factors for nonalcoholic fatty liver disease and fibrosis can help with management of their disease.
Cardiopulmonary Bypass for a Patient With Congenital Hyperinsulinemia
Authors: Crook Richard , Issitt Richard
Published: January 2018

Congenital hyperinsulinism is a clinical syndrome of pancreatic β-cell dysfunction characterized by failure to suppress insulin secretion in the presence of hypoglycemia. Here, we describe the concerns, the techniques used to ameliorate these potential problems, and the outcomes for a child with this condition undergoing cardiopulmonary bypass for correction of an atrial septal defect.
An Unusual Combination of Double Inlet Left Ventricle With Discordant Ventriculoarterial Connections and Bilateral Arterial Ducts
Authors: Alpat Safak , Crucean Adrian , Desai Tarak , McGuirk Simon , Anderson Robert H. , Botha Phil , Barron David
Published: January 2018

The presence of bilaterally persistent arterial ducts is an uncommon abnormality. Here, we describe the anatomy and successful management of an unusual patient with bilateral ducts in the setting of double inlet left ventricle, discordant ventriculoarterial connections, aortic atresia, and a severely hypoplastic and serpentine aortic arch.
Thromboelastography-based anticoagulation management during extracorporeal membrane oxygenation: a safety and feasibility pilot study
Authors: Panigada Mauro , E. Iapichino Giacomo , Brioni Matteo , Panarello Giovanna , Protti Alessandro , Grasselli Giacomo , Occhipinti Giovanna , Novembrino Cristina , Consonni Dario , Arcadipane Antonio , Gattinoni Luciano , Pesenti Antonio
Published: January 2018

Background

There is no consensus on the management of anticoagulation during extracorporeal membrane oxygenation (ECMO). ECMO is currently burdened by a high rate of hemostatic complications, possibly associated with inadequate monitoring of heparin anticoagulation. This study aims to assess the safety and feasibility of an anticoagulation protocol for patients undergoing ECMO based on thromboelastography (TEG) as opposed to an activated partial thromboplastin time (aPTT)-based protocol.

Methods

We performed a multicenter, randomized, controlled trial in two academic tertiary care centers. Adult patients with acute respiratory failure treated with veno-venous ECMO were randomized to manage heparin anticoagulation using a TEG-based protocol (target 16–24 min of the R parameter, TEG group) or a standard of care aPTT-based protocol (target 1.5–2 of aPTT ratio, aPTT group). Primary outcomes were safety and feasibility of the study protocol.

Results

Forty-two patients were enrolled: 21 were randomized to the TEG group and 21 to the aPTT group. Duration of ECMO was similar in the two groups (9 (7–16) days in the TEG group and 11 (4–17) days in the aPTT group, p = 0.74). Heparin dosing was lower in the TEG group compared to the aPTT group (11.7 (9.5–15.3) IU/kg/h vs. 15.7 (10.9–21.3) IU/kg/h, respectively, p = 0.03). Safety parameters, assessed as number of hemorrhagic or thrombotic events and transfusions given, were not different between the two study groups. As for the feasibility, the TEG-based protocol triggered heparin infusion rate adjustments more frequently (p < 0.01) and results were less frequently in the target range compared to the aPTT-based protocol (p < 0.001). Number of prescribed TEG or aPTT controls (according to study groups) and protocol violations were not different between the study groups.

Conclusions

TEG seems to be safely used to guide anticoagulation management during ECMO. Its use was associated with the administration of lower heparin doses compared to a standard of care aPTT-based protocol.

Trial registration ClinicalTrials.gov, October 22,2014. Identifier: NCT02271126.
Evaluation of Almitrine Infusion During Veno-Venous Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome in Adults
Authors: Esnault Pierre , Hraiech Sami , Bordes Julien , Forel Jean-Marie , Adda Mélanie , Rambaud Romain , Lehingue Samuel , Roch Antoine , Papazian Laurent , Guervilly Christophe
Published: January 2018

This single-center case series investigated the effect of almitrine infusion on Pao
2/fraction of inspired oxygen (Fio
2) in 25 patients on veno-venous extracorporeal membrane oxygenation for severe acute respiratory distress syndrome. A positive trial was defined as an increase of Pao
2/Fio
2 ratio ≥20%. Thirty-two trials were performed. Twenty (62.5%, 95% confidence interval, 37.5%–75%) trials in 18 patients were positive, with a median Pao
2/Fio
2 ratio increase of 35% (25%–43%). A focal acute respiratory distress syndrome and inhaled nitric oxide therapy were more frequent in patients with a positive response to almitrine. We observed no complications of almitrine use.
Identifying Novel Signaling Pathways: An Exercise Scientists Guide to Phosphoproteomics
Authors: Wilson Gary M. , Blanco Rocky , Coon Joshua J. , Hornberger Troy A.
Published: January 2018

We propose that phosphoproteomic-based studies will radically advance our knowledge about exercise-regulated signaling events. However, these studies use cutting-edge technologies that can be difficult for nonspecialists to understand. Hence, this review is intended to help nonspecialists 1) understand the fundamental technologies behind phosphoproteomic analysis and 2) use various bioinformatic tools that can be used to interrogate phosphoproteomic datasets.