Long-lasting renal dysfunction following tacrolimus induction therapy in ulcerative colitis patients.

Although tacrolimus (TAC) has remarkable effects in ulcerative colitis (UC) patients when given as remission induction therapy, some can develop renal dysfunction during TAC administration, resulting in withdrawal, though related details remain poorly understood. This study was conducted to determine the impact of oral TAC on renal function for remission induction therapy in UC patients. Fifty-five patients (10 elderly, 45 non-elderly) with UC and treated with oral TAC at our hospital were retrospectively evaluated. Renal function was assessed using estimated glomerular filtration rate (eGFR). Although a high clinical response to TAC was seen in both elderly and non-elderly, a decline in eGFR was noted in nearly all patients regardless of age, with a maximum change of -34.4% from the baseline value at week 11. Furthermore, eGFR decline recovered quickly after TAC discontinuation, though did not return to the baseline at two years following cessation. The rate of eGFR change at week 12 was significantly associated with patient age (ß = -0.3242, p = 0.0103) and peak serum trough level during TAC treatment (ß = 0.3563, p = 0.0051). Furthermore, the rate of decline in eGFR was significantly greater during treatment with TAC in the elderly as compared to non-elderly, with a large difference in eGFR decline rate between those groups also noted at two years after withdrawal of treatment. Careful attention to renal function when administering oral TAC for UC is important and changes in eGFR should be monitored closely in elderly patients even after treatment cessation.

Diagnostic utility of VEGF mRNA and SP1 mRNA expression in bronchial cells of patients with lung cancer.

BACKGROUND AND OBJECTIVE: Bronchial brushing is important for cytological diagnosis of lung carcinoma; however, cytological evaluation alone remains relatively insensitive. The aim of this study was to assess the diagnostic utility of vascular endothelial growth factor (VEGF) messenger ribonucleic acid (mRNA) and specificity protein 1 (SP1) mRNA in bronchial brushings in patients with or without lung cancer. METHODS: VEGF mRNA and SP1 mRNA were measured in liquid-based cells from bronchial brushings in patients with verified lung cancer (n = 93) and with benign lung disease that included tuberculosis (n = 51). This was done using the reverse-transcription polymerase chain reaction. RESULTS: Both VEGF mRNA and SP1 mRNA were significantly more likely to be expressed in the cancer group than in the control (benign) group, whatever their cell type. It was also more often found in the tuberculosis group than in the inflammation group (P < 0.01). In the cancer group, VEGF mRNA was significantly correlated with SP1 mRNA (P < 0.01). Of the 36 false negative cytology results, 30 gave positive results for VEGF mRNA and 34 for SP1 mRNA. The four false positive VEGF results were all diagnosed as tuberculosis. VEGF mRNA gave the highest diagnostic performance with serial use: sensitivity 89.2% and accuracy 90.3%. This was significantly better than cytology (P < 0.01). CONCLUSIONS: Detection of VEGF mRNA and SP1 mRNA in bronchial brushing cells may be used as an ancillary tool to cytological diagnosis for detection of early-stage lung cancer. It may also help distinguish tuberculosis from other causes of lung inflammation.

Transcription expression and clinical significance of dishevelled-3 mRNA and δ-catenin mRNA in pleural effusions from patients with lung cancer.

OBJECTIVE: To evaluate diagnostic utility of Dishevelled-3 (DVL-3) mRNA and δ-catenin mRNA expression in pleural effusions of patients with lung cancer. METHODS: DVL-3 mRNA and δ-catenin mRNA levels were assessed by performing RT-PCR on pleural effusion specimens from patients with lung cancer (n = 75) and with lung benign disease (n = 51). RESULTS: The expressions of DVL-3 mRNA and δ-catenin mRNA were significantly higher in malignant than in benign lung disease (P < 0.01) and were obviously higher than cytology in adenocarcinoma (P < 0.01). In single use, DVL-3 mRNA had the highest specificity (94.1%) and PPV (95.7%), whereas δ-catenin mRNA had the highest sensitivity (92.0%) and NPV (88.5%). When combinations of markers were evaluated together, DVL-3 mRNA and δ-catenin mRNA gave a high-diagnostic performance: sensitivity of 100.0%, NPV of 100.0%, and accuracy of 96.0%, respectively. CONCLUSION: As molecular markers of detecting pleural micrometastasis, DVL-3 mRNA and δ-catenin mRNA are helpful to diagnose the cancer cells in pleural effusions of patients with lung cancer.

The significance of detecting glucose transporter 1 and calretinin in serous effusions to differentiate between carcinoma cells and reactive mesothelial cells.

BACKGROUND: The cytologic evaluation of serous effusions to distinguish malignant cells from reactive mesothelial cells (RMCs)was an enormous challenge. The purpose of this study was to investigate the diagnostic value of glucose transporter 1 (GLUT1) and calretinin (CR) in serous effusions of patients with malignant and in order to significantly ameliorate the diagnostic accuracy. METHODS: The expressions of GLUT1 and CR were measured by streptavidin-peroxidase (S-P) immunocytochemical technique in serous effusions of 183 patients with malignant and in 95 patients with benign diseases. RESULTS: The positive ratio of GLUT1 was 91.8% (168/183) in serous effusions from patients with malignant and 5.3% (5/95) in benign diseases, they had a significant difference (P < .01). CR was expressed 89.5% (85/95) in benign diseases and 6.6% (12/183) in malignant, it also showed an important difference (P < 0.01). The combination of GLUT1 + CR revealed the best efficiency: the sensitivity and specificity were 100% and 98.9%, respectively. CONCLUSION: Immunocytochemical staining for GLUT1 and CR may be used as a complementary tool for the detection of malignant effusions and help to make a distinction between cancer cells and RMCs. The combination of GLUT1 and CR with immunocytochemistry stained can be achieved a higher diagnostic performance.

Down-Regulation of AHNAK2 Inhibits Cell Proliferation, Migration and Invasion Through Inactivating the MAPK Pathway in Lung Adenocarcinoma.

AHNAK nucleoprotein 2 (AHNAK2) has been emerged as a crucial protein for neuroblast differentiation and cell migration, thereby involving in the development of various cancers. However, the specific molecular mechanism of AHNAK2 in lung adenocarcinoma is inconclusive. By accessing to the Oncomine dataset and GEPIA website, a higher expression level of AHNAK2 was observed in lung adenocarcinoma tissue samples. Overall survival (OS) curve plotted by Kaplan-Meier method showed that up-regulation of AHNAK2 was related with poor prognosis of lung adenocarcinoma patients. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) analysis and western blot were conducted to examine the expression level of genes in lung adenocarcinoma cells. Through functional in vitro experiments, cell proliferation, migration and invasion were all suppressed after AHNAK2 knockdown using Cell counting kit-8 (CCK-8) assay, wound-healing and transwell analysis. Reduction of AHNAK2 decreased the apoptosis rate using flow cytometry analysis. Moreover, the key markers of MAPK pathway, p-MEK, p-ERK and p-P90RSK were decreased due to the transfection of si-AHNAK2 in A549 cells. U0126, a MEK inhibitor, showed the similar effects on MAPK-related protein levels with si-AHNAK2. To sum up, AHNAK2 is significantly increased in lung adenocarcinoma and plays a carcinogenic role by activating the MAPK signaling pathway, providing a novel insight and raising possibility for lung adenocarcinoma treatment.

Effects of chemoradiotherapy and chemotherapy on survival of patients with locally advanced pancreatic cancer: A meta-analysis of randomized controlled trials.

To comparatively evaluate chemoradiotherapy (CRT) and chemotherapy (CT) for the treatment of locally advanced pancreatic cancer (LAPC) by meta-analysis.A literature search was performed until August 2016 to identify comparative studies assessing survival rates and complications. Pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) were determined with the fixed or random effects model.Five randomized controlled trials (RCTs) met the defined inclusion criteria. A total of 593 patients were included, with 295 and 298 treated with CRT and CT, respectively. Overall survival showed no statistically significant difference in patients treated with CRT and CT at 6, 12, 18, and 24 months (respectively: OR = 1.13, 95% CI: 0.60-2.17; OR = 1.15, 95% CI: 0.53-2.52; OR = 1.13, 95% CI: 0.43-2.95; OR = 1.07, 95% CI: 0.67-1.72). Meanwhile, CRT had higher rates of grade 3 to 4 adverse events (nausea and vomiting, OR = 2.74, 95% CI: 1.36-5.52; diarrhea, OR = 4.28, 95% CI: 1.16-15.71).The data are not sufficient to change from CT to CRT in the treatment of patients with LAPC and thus clinical discretion is required until more data is accumulated.

Breast Metaplastic Squamous Cell Carcinoma Diagnosed with Fine Needle and Core Biopsy: A Case Study.

BACKGROUND Breast metaplastic squamous cell carcinoma (SCC) is a rare primary breast carcinoma, and overexpression of HER2 in this carcinoma is extremely uncommon. CASE REPORT We presented a case of a 48-year-old Asian female with breast metaplastic SCC. Fine needle aspiration biopsy (FNAB) and core needle biopsy (CNB) of the lesion were taken prior to surgical resection. FNAB smears demonstrated highly atypical squamous cells and a diagnosis positive for malignancy was rendered. CNB and a surgical resection specimen revealed invasive squamous carcinoma with keratin pearl formation and intercellular bridges. Further study demonstrated this was an unusual metaplastic SCC case with basal-HER2 (+) phenotype. HER2 has been linked to poor prognosis and response to therapy. CONCLUSIONS The pathological diagnosis of the breast metaplastic SCC was made initially by FNAB and CNB. Identification of basal-HER2 (+) phenotype was critical for selection of hormonal therapies and chemotherapy.

Diagnostic Utility of HPV16 E6 mRNA or E7 mRNA Quantitative Expression for Cervical Cells of Patients with Dysplasia and Carcinoma.

Current human papillomavirus (HPV)16 DNA testing has high sensitivity but low specificity, while mRNA testing (qualitative) improves the specificity. However, both techniques are not able to discriminate between transient and persistent infections. To overcome the disadvantages, we quantitatively detected E6 and E7 mRNAs by quantitative real-time polymerase chain reaction (qRT-PCR) in cervical brushing cells from 87 HPV16+ and 31 HPV16- patients. Our results showed that the expression levels of E6 mRNA or E7 mRNA were significantly increased in HPV16-positive cases than that in the negative cases. Furthermore, in HPV16+ cases, the expression levels of E6 mRNA were significantly increased in invasive cancer compared with high-grade squamous intraepithelial lesion (HSIL; p < 0.01), and HSIL compared with low-grade squamous intraepithelial lesion (LSIL; p < 0.01). There were no significant changes between LSIL and benign lesions. The expression levels of E7 mRNA presented no significant difference among the above-mentioned four groups. To test whether qRT-PCR can discriminate between transient and persistent infections, 57 HPV16+ patients were followed up for 1 year, and our results demonstrated that the expression levels of both E6 mRNA and E7 mRNA in the persistent infection group were significantly increased relative to the transient infection group ( p < 0.01 or 0.05). Thus, a quantitative detection of the expression levels of E6 mRNA in cervical brushing cells may not only be used as an ancillary tool to cytological diagnosis of cervical neoplasia, but may also help to determine the severity of the lesions and the triage of transient infection.

Expression and significance of MOC-31 and calretinin in pleural fluid of patients with lung cancer.

BACKGROUND: The cytologic assessment of pleural effusions to distinguish carcinoma cells from reactive mesothelial cells is particularly challenging. The aim of this study was to investigate the diagnostic value of monoclonal antibody (MOC-31) and calretinin in pleural fluid of patients with lung cancer to significantly improve the diagnostic accuracy. METHODS: The expressions of MOC-31 and calretinin were detected by means of S-P immunocytochemical technique in pleural effusions of patients with lung cancer (n = 92) and in patients with benign lung disease (n = 70). RESULTS: The positive rate of MOC-31 in pleural fluid was 90.2% (83/92) from patients with lung cancer and 2.9% (2/70) from patients with benign lung diseases, showing a significant difference (P < 0.01). Calretinin was expressed 87.1% (61/70) in benign lung diseases and 6.5% (6/92) in lung cancer, also showing a significant difference (P < 0.01). The optimal combination for assay was MOC-31 + calretinin: Sensitivity and specificity were 100 and 98.6%, respectively. CONCLUSION: MOC-31 and calretinin are of important clinical value for diagnosing and differentially diagnosing the cancer cells in pleural fluid of patients with lung cancer.

hTERT gene amplification and clinical significance in pleural effusions of patients with lung cancer.

PATIENTS AND METHODS: Human telomerase reverse transcriptase (hTERT) gene amplification was detected in pleural effusions of patients with lung cancer (n = 69) and in patients with benign lung disease (n = 46) when using a quantitative polymerase chain reaction (qPCR) technique. RESULTS: hTERT gene relative copy numbers were significantly higher in effusions from patients with malignant, adenocarcinoma and small-cell lung cancer than in effusions from patients with benign lung disease (P < .01). By using a threshold value of 1.39, hTERT gene amplification was significantly more frequent in malignant effusions compared with benign effusions and more likely to be positive for malignant effusions, compared with cytology (P < .01). The diagnostic performance of qPCR of hTERT gene amplification was significantly higher than that of cytology, in terms of sensitivity (91.3% vs. 56.5%), negative predictive value (87.8% vs. 60.5%), and accuracy (92.2% vs. 73.9%). CONCLUSIONS: Detecting hTERT gene amplification by qPCR appears suitable for distinguishing carcinoma cells from reactive mesothelial cells in pleural effusions. hTERT gene amplification was more sensitive than cytology and may be useful for diagnosing pleural micrometastases.

New Hg2+-selective chromo- and fluoroionophore based upon 8-hydroxyquinoline.

A new 8-hydroxyquinoline derivative having an appended boron-dipyrromethene function has been prepared, and its metal ion sensing properties were investigated. The designed compound exhibited pronounced Hg(2+)-selective on-off-type fluoroionophoric properties among the representative transition- and heavy-metal ions in aqueous dioxane solution. The fluorescence was efficiently quenched more than 98% with 5 equiv of Hg(2+) ions, and the detection limit was found to be 5 x 10(-)(6) M in a dioxane-water (1:3, v/v) solvent system. The ionophore also showed a selective chromogenic behavior toward Hg(2+) ions by changing the color of the solution from light amber to red, which can be detected with the naked eye.