Mutation in the tyrosine kinase domain of epidermal growth factor receptor is a predictive and prognostic factor for gefitinib treatment in patients with non-small cell lung cancer.

PURPOSE: Mutations in epidermal growth factor receptor (EGFR) can be used to predict the tumor response of patients receiving gefitinib for non-small cell lung cancer (NSCLC). We investigated the association between mutations in EGFR tyrosine kinase domain and tumor response and survival in gefitinib-treated NSCLC patients. EXPERIMENTAL DESIGN: EGFR mutations in exons 18 to 21 were analyzed by DNA sequencing of paraffin-embedded tumor tissues from gefitinib-treated NSCLC patients. The results were correlated with clinical variables. RESULTS: EGFR mutations were found in 61.1% (33 of 54) of cases; response rate and disease control rate were 56.8% and 68.5%, respectively. There was no significant difference in mutation rates between adenocarcinoma (29 of 43) and nonadenocarcinoma (4 of 11; P = 0.085). However, all four nonadenocarcinomas with EGFR mutations had no response to gefitinib. Presence of EGFR mutations was the only independent predictor for disease control (P = 0.003) and tumor response (P = 0.017) in multivariate analysis; positive predictive values were 87.9% and 70.8% and negative predictive values were 61.9% and 69.2%, respectively. In comparison with patients whose tumor was negative for EGFR mutations, patients with EGFR mutations had better progression-free survival (median, 7.6 versus 1.7 months; P = 0.011) and overall survival (median, 14.7 versus 4.7 months; P = 0.046). CONCLUSIONS: Mutations in EGFR tyrosine kinase correlate with treatment response and survival in gefitinib-treated NSCLC patients and can be used as a predictive and prognostic factor. Thus, analysis of EGFR tyrosine kinase mutations in lung adenocarcinoma is of clinical significance, as it can permit the customization of treatment with EGFR tyrosine kinase inhibitors.     

Pyometra as a lower abdominal doughnut sign on a Ga-67 scan

A 77-year-old woman was referred for Ga-67 scan to evaluate intermittent fever and chills that had lasted more than 20 days. The Ga-67 whole-body scan revealed a doughnut-shaped Ga-67 accumulation in the lower abdominal region. Combined Ga-67 and Tc-99m MDP bone scan confirmed that this activity was in the uterus, because the shape of the urinary bladder on bone scan was different from that of the Ga-67-avid lesion. Pyometra was proved during operation, and pus culture was performed.     

Upregulated hPuf-A promotes breast cancer tumorigenesis

hPuf-A is a member of RNA-binding PUF family that regulates mRNA translation. Redistribution of hPuf-A from the nucleolus to the nucleoplasm upon genotoxic stress modulates the poly(ADP-ribosyl)ation activity of PARP-1. Here, we report a novel function of hPuf-A involved in promoting breast cancer progression. Immunohistochemical studies showed higher expression levels of hPuf-A in stage I, II, III, and IV breast cancer specimens in contrast with those of hPuf-A in ductal carcinoma in situ. The presence of hPuf-A is highly associated with colony formation capacities in breast cancer T47D and MDA-MB-231 cells. Xenograft growth of hPuf-A-silenced and hPuf-A overexpressing MDA-MB-231 cells in nude mice was substantially in concert with colony formation capacities. This promoting effect of hPuf-A in tumorigenesis might be correlated with the regulation of its associated mRNAs, such as RbAp48 and DDX3. Collectively, hPuf-A may have diagnostic values in breast cancer progression.     

Significant elevation of antiviral activity of strictinin from Pu’er tea after thermal degradation to ellagic acid and gallic acid

Compared with abundant catechins, strictinin is a minor constituent in teas and has been demonstrated to possess inhibitory potency on influenza virus. In this study, strictinin was found as the major phenolic compound in Pu’er teas produced from leaves and buds of wild trees. Due to its thermal instability, strictinin, in tea infusion or in an isolated form, was completely decomposed to ellagic acid and gallic acid after being autoclaved for 7 minutes. A plaque reduction assay was employed to compare the relative inhibitory potency between strictinin and its thermally degraded products against human influenza virus A/ Puerto Rico/8/34. The results showed that the antiviral activity of ellagic acid regardless of the presence or absence of gallic acid was significantly higher than that of strictinin. Thermal degradation of strictinin to ellagic acid and gallic acid seems to be beneficial for the preparation of Pu’er teas in terms of enhancing antiviral activity.     

Energy-regulated molecules maintain young status in the trophocytes and fat cells of old queen honeybees

Queen honeybees (Apis mellifera) have much longer lifespans than worker bees. Energy-regulated molecules in the trophocytes and fat cells of workers during aging have been determined, but are unknown in queen bees. In the present study, energy-regulated molecules were evaluated in the trophocytes and fat cells of young and old queen bees. Adenosine monophosphate-activated protein kinase α2 (AMPK-α2), phosphorylated AMPK-α2 (pAMPK-α2), and cAMP-specific phosphodiesterases activity increased with aging. The pAMPK-α2/AMPK-α2 ratio and AMPK activity; adenosine triphosphate (ATP), adenosine diphosphate (ADP), and adenosine monophosphate (AMP) concentrations; the ADP/ATP ratio and the AMP/ATP ratio; the cyclic adenosine monophosphate concentration; forkhead box protein O expression; Silent information regulator T1 (SirT1) expression and activity; and peroxisome proliferator-activated receptor-α (PPAR-α) expression were not significantly different between young and old queen bees. These results show that energy-regulated molecules maintain a youthful status in the trophocytes and fat cells of queen bees during aging. These cells seem to have longevity-promoting mechanisms and may clarify the secret of longevity in queen bees.     

Novel identification of biofluids using a multiplex methylation-specific PCR combined with single-base extension system

Purpose

Knowledge of the composition of complex body fluid mixtures may aid forensic investigations greatly. However, many of the traditional tests are presumptive in nature and can lead to ambiguous results. The aim of this study is to establish a reliable method to identify various biofluids via analysis of their DNA methylation profiles.

Methods

A total of eight biofluid-specific methylated markers for saliva, venous blood, vaginal fluids, and semen were isolated from the open database of Infinium HumanMethylation450 BeadChip. These biofluid-specific markers, a control marker to confirm bisulfite conversion, and a gender marker, were combined into a 10-plex methylation-specific PCR single-base-extension (MSP-SBE) system.

Results

Analysis of 65 DNA samples isolated from venous blood, semen, vaginal fluid, saliva, and menstrual blood that had been treated with bisulfite, resulted in all eight markers detecting the body fluid to which they were designed. Unambiguous body fluid identification occurred from both single sources of body fluids and complex mixtures. A threshold was devised for each marker to minimize the chance of a false inclusion. The efficacy of the assay and application to forensic practice was demonstrated using five non-probative samples from real alleged sexual assault cases. The system unambiguously determined the biofluid types for the non-probative forensic samples that previously resulted in inconclusive or conflicting results using traditional tests.

Conclusions

The results demonstrated the 10-plex MSP-SBE system established in this study is both sensitive and specific when applied to body fluid identification and can be readily adopted into forensic practice.

     

Phyllodes Tumor of the Breast: The Challenge Persists

Introduction Phyllodes tumors of the breast are uncommon, and it is difficult to predict biologic behavior based on clinicopathologic features. Despite the wealth of data on the factors to predict recurrence, little is known about the impact of treatment refinements. This study seeks to define changes in patient characteristics, histopathologic parameters, and outcome between the two periods before and after the care of patients with breast diseases was centralized to a breast specialty. Methods The records of 182 patients with phyllodes tumors managed surgically were reviewed. Patients treated from 1985 to 1996 (n = 81) were compared with those seen from 1997 to 2004 (n = 101). Results The analysis of the two treatment periods revealed that there was a decrease in tumor size at diagnosis, from 7.7 cm during the earlier period to 4.6 cm during the recent period (P = 0.003). The patients undergoing breast-conserving surgery were significantly increased during the recent period. In contrast, pathologic features and local recurrence rates remained unchanged during the study period. Multivariate analysis revealed that positive surgical margin was the only independent predictor of recurrence, with an increased hazard of 8.0. Overall, upgrading to the next grade was observed in 16% of recurrences. Conclusions Breast-conserving surgery with clear margins is the current treatment of choice for phyllodes tumors, but this strategy does not further reduce local recurrence effectively. Optimal management continues to be a challenge.     

Unexpected rapid progression of metastatic adenoid cystic carcinoma during treatment with imatinib mesylate

BACKGROUND: There is a lack of effective treatment for metastatic adenoid cystic carcinoma (ACC), a usually indolent tumor. We studied the efficacy of imatinib mesylate, a potent inhibitor of KIT tyrosine kinase, in patients with KIT-positive metastatic ACC. METHOD: Five patients with lung metastasis were treated in a pilot study with imatinib 400 mg by mouth twice a day. Mutations of c-kit and platelet-derived growth factor receptor (PDGFR)-alpha in tumors from these patients were analyzed. RESULTS: Disease progression was noted in three of five patients during the short treatment periods, ranging from 2 to 3 weeks. Three patients died of disease within 6 months. No detectable mutations were found in c-kit and PDGFR-alpha. CONCLUSION: We observed an unexpected high progression rate of metastatic ACC within short periods during imatinib treatment. Use of imatinib to treat cancers without c-kit or PDGFR-alpha mutation should be approached with caution.     

Pseudomembranous tracheobronchitis caused by Aspergillus in immunocompromised patients

We report 2 cases of Aspergillus pseudomembranous tracheobronchitis in patients with diabetes. The first patient succumbed to progressive obstructive respiratory failure despite mechanical ventilation and antifungal therapy. However, the second patient survived. Aspergillus tracheobronchitis should be considered in immuno-compromised patients presenting with cough, chest pain, fever, dyspnea and upper airway obstruction. Early bronchoscopy and histologic examination should be performed. Early, appropriate treatment may be life saving.