HTDMA-modified bentonite clay for effective removal of Pb(II) from aqueous solution.

This work studies the Pb(II) removal onto bentonite clay modified by hexadecyl trimethyl ammonium bromide (HDTMA). Characterizations of the unmodified and modified materials were performed by using XRD, SEM, TG-DSC, FT-IR, and BET surface area analyses. Factors influencing the uptake of Pb(II) from aqueous solution, such as pHsolution, ion strength, uptake time, adsorbent dosage, and initial Pb(II) concentration, were examined. The obtained results showed that bentonite clay was successfully modified by HDTMA, resulting in an increase in its surface area by about 70 %. The Pb(II) adsorption onto modified bentonite clay reached equilibrium at pH = 5.0 after 120 min. Studies within the isotherm and kinetic models demonstrated that the adsorption followed the Sips isotherm and pseudo-second-order kinetic models. The maximum monolayer adsorption capacity calculated from the Langmuir model at 30 °C was 25.8 mg/g, which is much higher than that obtained for the unmodified sample (18.9 mg/g). The FT-IR and TG-DSC analyses indicated that the formation of inner-sphere complexes plays a fundamental role in the mechanism of Pb(II) uptake onto HDTMA-bentonite clay. This mechanism of Pb(II) adsorption was further investigated, for the first time, by using the positron annihilation lifetime (PAL) and electron momentum (EMD) measurements. The PAL and EMD analyses indicated that the existence of Al and Si mono-vacancies in the HDTMA-bentonite should have essential contributions to the adsorption mechanism. In particular, we found a very interesting mechanism that the Pb(II) adsorption should occur inside the interlayer spaces of the HDTMA-bentonite.

SCCRO promotes glioma formation and malignant progression in mice.

Originally identified as an oncogene activated by amplification in squamous cell carcinomas, several lines of evidence now suggest that squamous cell carcinoma-related oncogene (SCCRO; aka DCUN1D1) may play a role in the pathogenesis of a wide range of human cancers including gliomas. SCCRO's oncogenic function is substantiated by its ectopic expression, resulting in transformation of cells in culture and xenograft formation in nude mice. The aim of this study was to assess the in vivo oncogenicity of SCCRO in a murine model. Ubiquitous expression of SCCRO resulted in early embryonic lethality. Because SCCRO overexpression was detected in human gliomas, its in vivo oncogenic activity was assessed in an established murine glioma model. Conditional expression of SCCRO using a replication-competent ASLV long terminal repeat with splice acceptor/nestin-(tumor virus-A) tv-a model system was not sufficient to induce tumor formation in a wild-type genetic background, but tumors formed with increasing frequency and decreasing latency in facilitated background containing Ink4a deletion alone or in combination with PTEN loss. Ectopic expression of SCCRO in glial progenitor cells resulted in lower-grade gliomas in Ink4a(-/-) mice, whereas its expression in Ink4a(-/-)/PTEN(-/-) background produced high-grade glioblastoma-like lesions that were indistinguishable from human tumors. Expression of SCCRO with platelet-derived growth factor-beta (PDGF-beta) resulted in an increased proportion of mice forming glioblastoma-like tumors compared with those induced by PDGF-beta alone. This work substantiates SCCRO's function as an oncogene by showing its ability to facilitate malignant transformation and carcinogenic progression in vivo and supports a role for SCCRO in the pathogenesis of gliomas and other human cancers.

Epidermal growth factor receptor signaling in adenocarcinomas with bronchioloalveolar components.

BACKGROUND: Epidermal growth factor receptor (EGFR) has gained importance in non-small cell lung cancer given impressive responses to agents targeting this molecule, particularly in bronchioloalveolar carcinoma (BAC) and adenocarcinomas, mixed subtype, with BAC components (adeno/BAC). This study assesses EGFR signaling in these tumors. METHODS: One hundred fifty tumors were classified as BAC or adeno/BAC. Tumor marker expression was determined by immunohistochemistry. Correlations with expression were examined for all tumors (BAC and adeno/BAC), and by BAC and adeno/BAC subset analyses. RESULTS: Positive immunophenotype was observed in 40.6% of tumors for EGFR, 51.3% for p-AKT, 58.7% for p-ERK, and 28.0% for PTEN, with increased overexpression of EGFR (p = 0.025) and p-AKT (p < 0.0001) in adeno/BAC. Epidermal growth factor receptor immunophenotype was greater in never-smokers (p = 0.008) and correlated with improved overall survival (p = 0.018). On subset analysis, EGFR correlated with improved overall survival (p = 0.05) and disease-free interval (p = 0.044) only in adeno/BAC. Epidermal growth factor receptor independently predicted improved disease-free interval in adeno/BAC (p = 0.03; hazard ratio, 0.47; 95% confidence interval, 0.23 to 0.94). CONCLUSIONS: Overexpression of EGFR in lung adenocarcinomas with components of BAC histology correlate with never-smoker status and improved overall survival and disease-free interval. Epidermal growth factor receptor immunophenotype may be a useful predictor of clinical outcomes in this tumor subset.

Mutational analysis of EGFR and related signaling pathway genes in lung adenocarcinomas identifies a novel somatic kinase domain mutation in FGFR4.

BACKGROUND: Fifty percent of lung adenocarcinomas harbor somatic mutations in six genes that encode proteins in the EGFR signaling pathway, i.e., EGFR, HER2/ERBB2, HER4/ERBB4, PIK3CA, BRAF, and KRAS. We performed mutational profiling of a large cohort of lung adenocarcinomas to uncover other potential somatic mutations in genes of this signaling pathway that could contribute to lung tumorigenesis. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed genomic DNA from a total of 261 resected, clinically annotated non-small cell lung cancer (NSCLC) specimens. The coding sequences of 39 genes were screened for somatic mutations via high-throughput dideoxynucleotide sequencing of PCR-amplified gene products. Mutations were considered to be somatic only if they were found in an independent tumor-derived PCR product but not in matched normal tissue. Sequencing of 9MB of tumor sequence identified 239 putative genetic variants. We further examined 22 variants found in RAS family genes and 135 variants localized to exons encoding the kinase domain of respective proteins. We identified a total of 37 non-synonymous somatic mutations; 36 were found collectively in EGFR, KRAS, BRAF, and PIK3CA. One somatic mutation was a previously unreported mutation in the kinase domain (exon 16) of FGFR4 (Glu681Lys), identified in 1 of 158 tumors. The FGFR4 mutation is analogous to a reported tumor-specific somatic mutation in ERBB2 and is located in the same exon as a previously reported kinase domain mutation in FGFR4 (Pro712Thr) in a lung adenocarcinoma cell line. CONCLUSIONS/SIGNIFICANCE: This study is one of the first comprehensive mutational analyses of major genes in a specific signaling pathway in a sizeable cohort of lung adenocarcinomas. Our results suggest the majority of gain-of-function mutations within kinase genes in the EGFR signaling pathway have already been identified. Our findings also implicate FGFR4 in the pathogenesis of a subset of lung adenocarcinomas.

Thoracoscopic lobectomy facilitates the delivery of chemotherapy after resection for lung cancer.

BACKGROUND: We conducted a study of patients who underwent anatomic resection with adjuvant chemotherapy to determine if thoracoscopic lobectomy enables more effective administration of adjuvant chemotherapy than lobectomy by thoracotomy. METHODS: We reviewed the outcomes of 100 consecutive patients with non-small cell lung cancer (NSCLC) who underwent lobectomy and received adjuvant chemotherapy (1999 to 2004). The variables analyzed were time to initiation of chemotherapy, percentage of planned regimen received, number of delayed or reduced chemotherapy doses, toxicity grade, length of hospitalization, chest tube duration, 30-day mortality, and major complications (pneumonia, respiratory failure, atrial fibrillation). The chi2 test and Student t test were used to compare dichotomous and continuous variables, respectively. RESULTS: Complete resection was performed by thoracotomy in 43 patients and by thoracoscopy in 57 (no conversions). All patients received adjuvant chemotherapy, and 20 (20%) received adjuvant radiation therapy: 13 (30%) of 43 in the thoracotomy group and 7 (12%) of 57 in the thoracoscopy group (p = 0.04). Patients undergoing thoracoscopic lobectomy had significantly fewer delayed (18% versus 58%, p < 0.001) and reduced (26% versus 49%, p = 0.02) chemotherapy doses. A higher percentage of patients undergoing thoracoscopic resection received 75% or more of their planned adjuvant regimen without delayed or reduced doses (61% versus 40%, p = 0.03). There were no significant differences in time to initiation of chemotherapy or toxicity. Patients undergoing a thoracoscopic lobectomy had a shorter median length of hospitalization (4 days versus 5 days, p = 0.02). CONCLUSIONS: Thoracoscopy was associated with an overall higher compliance rate and fewer delayed or reduced doses of chemotherapy in patients receiving adjuvant chemotherapy.

Thoracoscopic lobectomy: a safe and effective strategy for patients receiving induction therapy for non-small cell lung cancer.

BACKGROUND: Thoracoscopic lobectomy is an accepted oncologic approach for early stage non-small cell lung cancer (NSCLC). We conducted a retrospective study of patients who underwent lobectomy after induction therapy to determine the feasibility of thoracoscopic lobectomy compared with conventional thoracotomy lobectomy. METHODS: The outcomes of 97 consecutive patients with NSCLC who received induction therapy followed by lobectomy from 1996 to 2005 were reviewed. Outcome variables analyzed included complete resection, chest tube duration, length of hospitalization, 30-day mortality, hemorrhage, pneumonia, respiratory failure, and other major complications. The Student t test and chi2 or RxC contingency tables were used to compare continuous and categoric variables, respectively. RESULTS: Lobectomy was performed by thoracotomy in 85 patients and thoracoscopically in 12 patients (1 conversion), with complete resection in all patients. All patients received induction chemotherapy, and 74 (76%) received induction radiotherapy as well: 66 of 85 (78%) in the thoracotomy group and 8 of 12 (67%) in the thoracoscopy group. The overall median survival was 2.3 years, with no difference between the groups. Patients undergoing a thoracoscopic lobectomy had a shorter median hospital stay (3.5 vs 5 days, p = 0.0024) and chest tube duration (2 vs 4 days, p < 0.001). There were no significant differences in 30-day mortality, hemorrhage, pneumonia, or respiratory failure. CONCLUSIONS: Thoracoscopic lobectomy is a feasible approach for selected patients undergoing resection after induction therapy, and is associated with shorter hospital stay and chest tube duration. Long-term follow-up of survival will determine the role of thoracoscopic lobectomy in the management of patients after induction therapy.

Use of cigarette-smoking history to estimate the likelihood of mutations in epidermal growth factor receptor gene exons 19 and 21 in lung adenocarcinomas.

PURPOSE: Lung adenocarcinomas with mutations in exons 19 and 21 of the epidermal growth factor receptor gene (EGFR) demonstrate sensitivity to gefitinib or erlotinib. Investigators have reported an association between EGFR mutations and the amount and duration of cigarette smoking, with the highest incidence of mutations seen in never smokers. METHODS: EGFR exon 19 and 21 mutation status was determined in 265 tumor samples using direct sequencing, polymerase chain reaction (PCR), or PCR-based restriction fragment length polymorphism analysis. A detailed smoking history was obtained. Patients were categorized as never smokers (< 100 lifetime cigarettes), former smokers (quit > or = 1 year ago), or current smokers (quit < 1 year ago). RESULTS: We detected EGFR mutations in 34 (51%) of 67 never smokers (95% CI, 38% to 64%), 29 (19%) of 151 former smokers (95% CI, 13% to 27%), and two (4%) of 47 current smokers (95% CI, 1% to 16%). Significantly fewer EGFR mutations were found in people who smoked for more than 15 pack-years (P < .001) or stopped smoking less than 25 years ago (P < .02) compared with individuals who never smoked. The number of smoking pack-years and smoke-free years predicted the prevalence of EGFR mutations (areas under receiver operating characteristic curve = 0.78 and 0.77, respectively). CONCLUSION: The likelihood of EGFR mutations in exons 19 and 21 decreases as the number of pack-years increases. Mutations were less common in people who smoked for more than 15 pack-years or who stopped smoking cigarettes less than 25 years ago. These data can assist clinicians in assessing the likelihood of exon 19 and 21 EGFR mutations in patients with lung adenocarcinoma when mutational analysis is not feasible.

Clinical course of patients with non-small cell lung cancer and epidermal growth factor receptor exon 19 and exon 21 mutations treated with gefitinib or erlotinib.

PURPOSE: In patients with non-small cell lung cancer (NSCLC), mutations in the epidermal growth factor receptor (EGFR) tyrosine kinase domain have been associated with sensitivity to erlotinib and gefitinib. We undertook this study to explore the relationship between EGFR mutation type and clinical variables, including treatment with gefitinib and erlotinib. EXPERIMENTAL DESIGN: In patients with NSCLC, EGFR exon 19 deletion mutations and EGFR L858R point mutations were analyzed by nonsequencing PCR-based methods from paraffin blocks of tissue obtained before treatment. The results were correlated with clinical information (sex, pathologic subtype, race/ethnicity, treatment, and overall survival). RESULTS: The two most common EGFR mutations were identified in 24% (70 of 291; 95% confidence interval, 26%-38%) of tumors from patients with NSCLC. EGFR mutation was associated with Asian ethnicity (P = 0.0023) and being a "never smoker" (P = 0.0001). Among patients with EGFR mutations, 39% (27 of 70) had EGFR L858R, whereas 61% (43 of 70) had an EGFR exon 19 deletion. After treatment with erlotinib (n = 12) or gefitinib (n = 22), patients with EGFR mutations had a median overall survival of 20 months. After treatment with erlotinib or gefitinib, patients with EGFR exon 19 deletions had significantly longer median survival than patients with EGFR L858R (34 versus 8 months; log-rank P = 0.01). CONCLUSIONS: EGFR mutations in exons 19 or 21 are correlated with clinical factors predictive of response to gefitinib and erlotinib. Those with EGFR exon 19 deletion mutations had a longer median survival than patients with EGFR L858R point mutation. These observations warrant confirmation in a prospective study and exploration of the biological mechanisms of the differences between the two major EGFR mutations.

SCCRO expression correlates with invasive progression in bronchioloalveolar carcinoma.

BACKGROUND: Overexpression of squamous cell carcinoma-related oncogene (SCCRO) is associated with invasive progression and poor outcomes in non-small cell lung cancer. We assessed the role of SCCRO as a tumor marker in bronchioloalveolar carcinoma (BAC), a subtype of adenocarcinoma exhibiting evidence of histologic tumor progression. We hypothesized that SCCRO expression would correlate with invasive tumor phenotypes and worse survival in BAC. METHODS: We classified 150 tumors as pure BAC, BAC with focal invasion, or adenocarcinoma with BAC features. A tissue microarray was constructed from areas of benign lung, BAC, and invasive adenocarcinoma in these tumors. Squamous cell carcinoma-related oncogene expression was graded by immunohistochemistry from 0 to 3 (absent, low, moderate, or high), with positive SCCRO phenotype defined as grade 3. Squamous cell carcinoma-related oncogene specificity was determined by Wilcoxon rank test and area under the receiver-operator curve, survival by the Kaplan-Meier method, and correlation with prognostic factors by log-rank test. RESULTS: Of the 86.0% (129 of 150) of specimens suitable for analysis, positive SCCRO phenotype was seen in 16.3% (21 of 129) and was 100.0% specific for tumor versus benign tissue (area under receiver-operator curve, 0.92). Positive SCCRO phenotype was greater in tumors with increasing degrees of invasive histologic type (7.0% pure BAC, 13.6% BAC with focal invasion, and 28.6% adenocarcinoma with BAC features; p = 0.02). Low-level SCCRO expression was present in 83.9% (99 of 118) of benign tissues and correlated with tobacco use and poor survival (p = 0.05). CONCLUSIONS: Squamous cell carcinoma-related oncogene is a marker of invasive tumor progression in BAC. Low-level expression in adjacent benign lung predicts worse survival, and may represent field cancerization or host-tumor effects.