Comparison of limited surgery and three-dimensional conformal radiation in high-risk patients with stage I non-small cell lung cancer.

Introduction: Anatomic resection is currently the standard of care for patients with stage I non-small cell lung cancer (NSCLC). Some stage I patients are unable to tolerate lobectomy because of limited lung function or prohibitive comorbidities. In this study, we retrospectively compared the outcome of patients treated with wedge resection or three-dimensional (3-D) conformal radiation therapy, the most common treatment modalities used for such high-risk patients.

Fragile histidine triad-mediated tumor suppression of lung cancer by targeting multiple components of the Ras/Rho GTPase molecular switch.

The fragile histidine triad (FHIT) gene has been shown to function as a tumor suppressor gene in vitro and in vivo. However, the mechanism of its action is still largely unknown. To elucidate the molecular mechanism and biological pathway in FHIT-mediated tumor suppression, we used a complementary gene and protein expression profiling with DNA microarray and ProteinChip technologies to quantitatively monitor cellular changes in gene and protein expression and discover the molecular targets of FHIT in non-small cell lung carcinoma (NSCLC) cells.

Proliferative changes in the bronchial epithelium of former smokers treated with retinoids.

Background: Retinoids have shown antiproliferative and chemopreventive activity. We analyzed data from a randomized, placebo-controlled chemoprevention trial to determine whether a 3-month treatment with either 9-cis-retinoic acid (RA) or 13-cis-RA and alpha-tocopherol reduced Ki-67, a proliferation biomarker, in the bronchial epithelium.

Methods: Former smokers (n = 225) were randomly assigned to receive 3 months of daily oral 9-cis-RA (100 mg), 13-cis-RA (1 mg/kg) and alpha-tocopherol (1200 IU), or placebo.

Outcomes after extrapleural pneumonectomy and intensity-modulated radiation therapy for malignant pleural mesothelioma.

Background: Malignant pleural mesothelioma is a locally aggressive tumor that is usually fatal. Extrapleural pneumonectomy (EPP) followed by hemithoracic irradiation has shown promise, but local failure remains a significant problem. To improve local control, we have used intensity-modulated radiation therapy (IMRT) as it allows better dose distribution to regions at risk of recurrence as well as reduced radiation to surrounding organs.

The double-stranded RNA-activated protein kinase mediates radiation resistance in mouse embryo fibroblasts through nuclear factor kappaB and Akt activation.

Purpose: Activation of the double-stranded RNA-activated protein kinase (PKR) leads to the induction of various pathways including the down-regulation of translation through phosphorylation of the eukaryotic translation initiation factor 2alpha (eIF-2alpha). There have been no reports to date about the role of PKR in radiation sensitivity.

Experimental Design: A clonogenic survival assay was used to investigate the sensitivity of PKR mouse embryo fibroblasts (MEF) to radiation therapy.

Use of aprotinin in extrapleural pneumonectomy: effect on hemostasis and incidence of complications.

Background: The purpose of this study was to examine the effect of aprotinin on blood loss in extrapleural pneumonectomy and to identify potential treatment-related complications.

Methods: Between March 1, 1999, and July 1, 2004, 27 (52%) of 52 patients who underwent extrapleural pneumonectomy received half-dose aprotinin (1 million kallikrein inhibition units load; 250,000 kallikrein inhibition units per hour infusion). A retrospective data review and analysis were performed.

Sarcomatoid carcinoma of the lung: a predictor of poor prognosis.

Background: Sarcomatoid cancer (SARC) of the lung is a rare histologic type of non-small cell lung cancer (NSCLC). Although believed to be associated with poor prognosis, its effect on survival and recurrence has not been well defined. Our goal was to determine the prognostic significance of SARC histology in patients undergoing pulmonary resection.

Long-term results of RTOG trial 8911 (USA Intergroup 113): a random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer.

Purpose: We update Radiation Therapy Oncology Group trial 8911 (USA Intergroup 113), a comparison of chemotherapy plus surgery versus surgery alone for patients with localized esophageal cancer. The relationship between resection type and between tumor response and outcome were also analyzed.

Patients And Methods: The chemotherapy group received preoperative cisplatin plus fluorouracil.

Proposed modification of nodal status in AJCC esophageal cancer staging system.

Background: The current American Joint Committee on Cancer (AJCC) esophageal cancer staging for nodal status is difficult to interpret and is based solely on lymph node location relative to the primary tumor's esophageal location. Recent reports suggest that the number of lymph nodes involved is also an important factor. We reviewed our esophageal experience to propose an improved nodal staging system.

Tumor-specific activation of human telomerase reverses transcriptase promoter activity by activating enhancer-binding protein-2beta in human lung cancer cells.

The up-regulated expression and telomerase activity of human telomerase reverse transcriptase (hTERT) are hallmarks of tumorigenesis. The hTERT promoter has been shown to promote hTERT gene expression selectively in tumor cells but not in normal cells. However, little is known about how tumor cells differentially activate hTERT transcription and induce telomerase activity.

Stereotactic body radiation therapy for stage I non-small cell lung cancer.

Image-guided SBRT with the delivery of a BED greater than 100 Gy is feasible and safe in the treatment of peripherally located inoperable stage I NSCLC. The 3- to 5-year local control and overall survival rates for SBRT seem to be much better than the rates for conventional radiotherapy, and the toxicity rate is minimal. Particularly for stage Ia (T1N0M0) disease, survival rates with SBRT were comparable with rates seen with surgical resection.

Tumor suppressor 101F6 and ascorbate synergistically and selectively inhibit non-small cell lung cancer growth by caspase-independent apoptosis and autophagy.

101F6 is a candidate tumor suppressor gene harbored on chromosome 3p21.3, a region with frequent and early allele loss and genetic alterations in many human cancers. We previously showed that enforced expression of wild-type 101F6 by adenoviral vector-mediated gene transfer significantly inhibited tumor cell growth in 3p21.

A peptide selected by biopanning identifies the integrin alphavbeta6 as a prognostic biomarker for nonsmall cell lung cancer.

The development of new modes of diagnosis and targeted therapy for lung cancer is dependent on the identification of unique cell surface features on cancer cells and isolation of reagents that bind with high affinity and specificity to these biomarkers. We recently isolated a 20-mer peptide which binds to the lung adenocarcinoma cell line, H2009, from a phage-displayed peptide library. We show here that the cellular receptor for this peptide, TP H2009.

Propensity-matched analysis of three techniques for intrathoracic esophagogastric anastomosis.

Background: A cervical side-to-side stapled esophagogastric anastomosis appears to decrease morbidity compared with traditional hand-sewn techniques. We evaluated our experience with this novel technique in intrathoracic anastomoses and compared the outcome with circular-stapled or hand-sewn techniques.

Methods: All patients undergoing transthoracic esophagectomy from 1999 to 2005 for esophageal cancer with gastric replacement were reviewed.

Induction of apoptosis by tumor suppressor FHIT via death receptor signaling pathway in human lung cancer cells.

FHIT is a novel tumor suppressor gene located at human chromosome 3p14.2. Restoration of wild-type FHIT in 3p14.

Synergistic tumor suppression by coexpression of FUS1 and p53 is associated with down-regulation of murine double minute-2 and activation of the apoptotic protease-activating factor 1-dependent apoptotic pathway in human non-small cell lung cancer cells.

FUS1 is a novel tumor suppressor gene identified in human chromosome 3p21.3 region. Loss of expression and deficiency of posttranslational modification of FUS1 protein have been found in a majority of human lung cancers.

Aberrant promoter methylation profile and association with survival in patients with non-small cell lung cancer.

Purpose: The aim of this study was to investigate the prognostic value of hypermethylation of tumor suppressor genes in patients with non-small cell lung cancer (NSCLC).

Experimental Design: We examined the methylation status of nine genes in 155 tumors from patients with NSCLC using quantitative methylation-specific PCR. We analyzed the associations between gene methylation status and overall patient survival.

Management of intrathoracic leaks following esophagectomy.

Mortality from esophageal anastomotic leaks has declined dramatically in contemporary practice, which seems to be caused by a management strategy that includes observation of contained, asymptomatic leaks, operation on uncontained leaks using muscle flaps to reinforce the leak repair, and percutaneous drainage of contained, symptomatic leaks. With further advances in surgical technique, critical care, and multimodality treatment, this trend is likely to continue.

Increased risk of aspiration and pulmonary complications after lung resection in head and neck cancer patients.

Background: Patients with head and neck cancers (HNCs) may have impaired deglutition and airway protection. The risk of pulmonary complications after lung resection has not been evaluated in HNC patients. We therefore reviewed the risk of aspiration-related pulmonary complications in HNC patients after pulmonary resection.

The 3p21.3 tumor suppressor NPRL2 plays an important role in cisplatin-induced resistance in human non-small-cell lung cancer cells.

NPRL2 is one of the novel candidate tumor suppressor genes identified in the human chromosome 3p21.3 region. The NPRL2 has shown potent tumor suppression activity in vitro and in vivo and has been suggested to be involved in DNA mismatch repair, cell cycle checkpoint signaling, and regulation of the apoptotic pathway.

Adenovirus-mediated transfer of human papillomavirus 16 E6/E7 antisense RNA and induction of apoptosis in cervical cancer.

Objective: In most cervical cancers, human papillomaviruses (HPVs) are identified. The E6 and E7 genes of HPVs encode proteins, that interfere with the function of the tumor suppressor proteins p53 and Rb. We are exploring the potential use of antisense HPV RNA transcripts for gene therapy for HPV-positive cervical cancers.

The addition of induction chemotherapy to preoperative, concurrent chemoradiotherapy improves tumor response in patients with esophageal adenocarcinoma.

Background: Tumor viability assessed by pathologic analysis of resected specimens in patients with preoperatively treated esophageal adenocarcinoma (EAC) is a prognostic indicator. The feasibility of induction chemotherapy followed by concurrent chemoradiotherapy (CCRT) and surgery for patients with locoregionally advanced EAC has been demonstrated. In this study, the authors evaluated the efficacy of CCRT compared with traditional concurrent chemoradiotherapy (CRT).

A rapid and efficient method for purification of recombinant adenovirus with arginine-glycine-aspartic acid-modified fibers.

Recombinant adenoviral vectors (adenovectors) have been subject to various genetic modifications to improve their transduction efficiency and targeting capacity. Production and purification of adenovectors with modified capsid proteins can be problematic using conventional two-cycle CsCl gradient ultracentrifugation. We have developed a new method for purifying recombinant adenovectors in two steps: iodixanol discontinuous density gradient ultracentrifugation and size exclusion column chromatography.

Comparison of clinical stage, therapy response, and patient outcome between squamous cell carcinoma and adenocarcinoma of the esophagus.

Purpose: To analyze the differences in clinical stage, pathologic response to chemoradiotherapy, patterns of failure, and overall survival (OS) between patients with squamous cell carcinoma (SCC) and adenocarcinoma (ACA) of the esophagus.

Patients And Methods: We stratified patients by two histologies, ACA and SCC, and statistically compared their clinical stage, post-therapy pathologic response, patterns of failure, and OS.

Results: Of the 235 patients who underwent preoperative chemoradiotherapy, 42 (18%) had SCC and 193 (82%) had ACA.