First-line chemotherapy for advanced-stage non-small-cell lung cancer: focus on docetaxel

Systemic chemotherapy results in modest improvements in survival and quality of life for patients with advanced-stage non-small-cell lung cancer (NSCLC). Administration of a platinum compound in combination with a taxane (paclitaxel or docetaxel), gemcitabine, vinorelbine, or irinotecan is considered optimal first-line therapy for patients with advanced-stage NSCLC who have a good performance status. Studies that have compared various platinum agent-based doublet regimens have demonstrated comparable efficacy between these regimens. In addition, non-platinum agent-based regimens have also demonstrated response rates and survival similar to the platinum agent-based combinations. These developments have allowed for tailoring of chemotherapy to individual patients based on factors such as toxicity profile, treatment schedule, and cost. Docetaxel is approved for first-line therapy and salvage treatment of advanced-stage NSCLC. Multiple randomized clinical trials have established the efficacy of platinum-agent/docetaxel regimens for first-line treatment of advanced-stage NSCLC. Improvements in various lung cancer-related symptoms and global quality of life indices have been noted with docetaxel-based regimens. Combination chemotherapy appears to be beneficial even for elderly patients. The current generation of clinical trials is evaluating the incorporation of molecularly targeted agents into existing 2-drug chemotherapy regimens. This article will discuss the role of docetaxel as first-line chemotherapy for patients with advanced-stage NSCLC.     

G, N, and P gene-based analysis of Chandipura viruses, India

An encephalitis outbreak in 2003 in children from India was attributed to Chandipura virus. Sequence analyses of G, N, and P genes showed 95.6%-97.6% nucleotide identity with the 1965 isolate (G gene, 7-11 amino acid changes); N and P genes were highly conserved.     

HPV-associated carcinoma of esophagus in the young: a case report and review of literature

Esophageal carcinoma (EC) is rare in the younger age group, with only 15 cases reported in world literature. It is even rarer for an etiological agent to be implicated.A case of a 15-yr-old boy with squamous cell carcinoma of the esophagus is reported. Human papillomavirus (HPV) 16 DNA sequences were detected in the neoplasm and the adjacent mucosa by polymerase chain reaction followed by restriction fragment length polymorphism (PCR-RFLP). The adjacent mucosa also showed virus-induced changes.     

Virtual bronchoscopy for diagnosis of inhalation injury in burnt patients

Virtual bronchoscopy using a multislice CT scanner, is a new non-invasive imaging technique and its utility in the diagnosis of inhalation injury in burnt patients has not been reported in literature yet. Initial experience of technique is encouraging and it merits more interest. It overcomes many of the limitations of the presently established procedure of fibreoptic bronchoscopy. Ten burned patients with clinical suspicion of inhalation injury underwent this investigation and in eight of these the diagnosis was confirmed.     

Incidence of primary neoplasms in explanted lungs: long-term follow-up from 214 lung transplant patients

BACKGROUND: Undetected neoplasms in explanted lungs at transplantation are an unusual occurrence that may significantly complicate both the short- and long-term outcome of these patients. The incidence and survival of undetected primary neoplasms in explanted lungs with clinical and radiologic correlation have not been studied in a large cohort of patients. METHODS: We reviewed the files of 214 consecutive lung transplants from the Transplant Center at the Cleveland Clinic Foundation from 1991 to 2000. Data collected included age, gender, pathology of explanted lung, and survival. Retrospective review of all imaging studies was performed in those cases where a primary neoplasm was detected after transplant. RESULTS: One hundred thirteen males and 101 females underwent lung transplantation for the following diagnoses: emphysema, 118; cystic fibrosis, 35; primary pulmonary hypertension, 27; usual interstitial pneumonia, 26; lymphangioleiomyomatosis, 4; sarcoidosis, 2; and pneumoconiosis, 2. Four neoplasms were found in the explanted lungs, representing a 2% incidence. All four neoplasms were bronchogenic carcinomas, including three adenocarcinomas and one squamous cell carcinoma. Three of four neoplasms were found in the setting of emphysema and were detected at an early stage (stage I), and the fourth presented as stage IV in the setting of usual interstitial fibrosis. No recurrence of tumor was seen in the stage I cases. The stage IV case died in the perioperative period. Retrospective review of the imaging studies showed that, in all four cases, a portable chest radiograph performed immediately before transplant failed to identify the lesions. A chest computerized tomogram was performed in all four cases from 3 to 27 months prior to transplantation and revealed a suspicious lesion in one of the four. CONCLUSIONS: Undetected neoplasms in explanted lungs at transplantation are uncommon, with an incidence of 2% at our institution. Adenocarcinoma was the most common cell type. In long-term survivors, no recurrences were found. The 3-year survival was 50% and this approaches the 3-year survival of transplant recipients without lung tumors (58.8%) at our institution. Chest radiographs appear to have a very low sensitivity for the detection of small lesions suspicious for a neoplasm. Chest computerized tomograms performed immediately prior to transplantation may be of benefit in detecting these neoplasms.     

Cryopreservation of stem cells using trehalose: evaluation of the method using a human hematopoietic cell line

While stem cell cryopreservation methods have been optimized using dimethylsulfoxide (DMSO), the established techniques are not optimal when applied to unfertilized human embryonic cells. In addition, important questions remain regarding the toxicity and characteristics of DMSO for treatment of stem cells for clinical use. The objective of this study was to establish an optimal method for cryopreservation of stem cells using low concentrations (0.2 M) of trehalose, a nontoxic disaccharide of glucose, which possesses excellent protective characteristics, in place of current methods utilizing high concentrations (1-2 M) of DMSO. A human hematopoietic cell line was used in this investigation as a surrogate for human stem cells. Trehalose was loaded into cells using a genetically engineered mutant of the pore-forming protein alpha-hemolysin from Staphylococcus aureus. This method results in a nonselective pore equipped with a metal-actuated switch that is sensitive to extracellular zinc concentrations, thus permitting controlled loading of trehalose. Preliminary experiments characterized the effects of poration on TF-1 cells and established optimal conditions for trehalose loading and cell survival. TF-1 cells were frozen at 1 degrees C/min to -80 degrees C with and without intra- and extracellular trehalose. Following storage at -80 degrees C for 1 week, cells were thawed and evaluated for viability, differentiation capacity, and clonogenic activity in comparison to cells frozen with DMSO. Predictably, cells frozen without any protective agent did not survive freezing. Colony-forming units (CFU) generated from cells frozen with intra- and extracellular trehalose, however, were comparable in size, morphology, and number to those generated by cells frozen in DMSO. There was no observable alteration in phenotypic markers of differentiation in either trehalose- or DMSO-treated cells. These data demonstrate that low concentrations of trehalose can protect hematopoietic progenitors from freezing injury and support the concept that trehalose may be useful for freezing embryonic stem cells and other primitive stem cells for therapeutic and investigational use.