Outcomes after neoadjuvant or adjuvant chemotherapy for cT2-4N0-1 non–small cell lung cancer: A propensity-matched analysis

Objective

Comparative survival between neoadjuvant chemotherapy and adjuvant chemotherapy for patients with cT2-4N0-1M0 non–small cell lung cancer has not been extensively studied.

The epidemiology of traumatic rupture of the thoracic aorta in children: a 13-year review

Traumatic rupture of the thoracic aorta (TRA) is a rare but highly lethal injury in children that occurs as a result of car versus pedestrian accidents and motor vehicle accidents. TRA is often associated with life-threatening injuries to other organ systems. Therefore children with TRA like adults sustaining TRA must be treated urgently but systematically. The rarity of this injury makes it all the more important for physicians treating pediatric trauma victims to be cognizant of the importance of the injury and the clinical and radiographic signs. Even when TRA is promptly recognized in children it is associated with a high in-hospital mortality. The proper use of child restraint systems and adherence to the 55 M.P.H. speed limit may be important factors in reducing the mortality of TRA in children after MVA.     

Vasopressin induced rhythmic activity in rat basilar artery

The effects of vasopressin on membrane potential and tension were studied in isolated segments of basilar arteries from the University of Iowa colonies of normotensive inbred Kyoto-Wistar rats (WKY) and stroke-prone spontaneously hypertensive rats (SP-SHR). In the presence of vasopressin (0.01–0.3 IU/ml), basilar arteries from WKY, but not from SP-SHR, developed rhythmic contractions. These contractions were recorded in 13 of 14 WKY basilar arteries, were unaffected by pretreatment with 6-hydroxydopamine, and were characterized by 20–100 dyne oscillations in tension, occurring 1–3 cycles/min, and superimposed on the vasopressin-induced contraction (averaging 60 dynes at 0.01 IU/ml or 160 dynes at 0.3 IU/ml). However, resting membrane potentials were not different in SP-SHR vs. WKY at 37°C, and both strains showed about the same (11 mV) depolarization by 0.1 IU/ml of vasopressin. The rhythmic contractions were enhanced by K⁺-free solution, and abolished in the presence of high K⁺ solution (30 mM), suggesting that active Na⁺−K⁺ transport may be involved in modulating the rhythmic activity. These findings are consistent with the hypothesis that the vasopressin-induced rhythmic contractions in WKY basilar arteries are at least partly dependent on a reduced activity of electrogenic Na⁺−K⁺ active transport in WKY as compared to SP-SHR. This research was supported by Grant Nos. HL14388 and HL16328 from the National Institutes of Health. Dr. Rusch is the recipient of Postdoctoral Fellowship HL06907.     

Freshly isolated bovine coronary endothelial cells do not express the BKca channel gene

Recent reports have suggested that different types of Ca²⁺-activated K⁺ channels may be selectively expressed either in the vascular endothelial cells (ECs) or smooth muscle cells (SMCs) of a single artery. In this study, we directly compared mRNA, protein and functional expression of the high-conductance Ca²⁺-activated K⁺ (BK_Ca) channel between freshly isolated ECs and SMCs from bovine coronary arteries. Fresh ECs and SMCs were enzymatically isolated, and their separation verified by immunofluorescent detection of α-actin and platelet/endothelium cell adhesion molecule (PECAM) proteins, respectively. Subsequently, studies using a sequence-specific antibody directed against the pore-forming α-subunit of the BK_Ca channel only detected its expression in the SMCs, whereas PECAM-positive ECs were devoid of the α-subunit protein. Additionally, multicell RT-PCR performed using cDNA derived from either SMCs or ECs only detected mRNA encoding the BK_Caα-subunit in the SMCs. Finally, whole-cell recordings of outward K⁺ current detected a prominent iberiotoxin-sensitive BK_Ca current in SMCs that was absent in ECs, and the BK_Ca channel opener NS 1619 only enhanced K⁺ current in the SMCs. Thus, bovine coronary SMCs densely express BK_Ca channels whereas adjacent ECs in the same artery appear to lack the expression of the BK_Ca channel gene. These findings indicate a cell-specific distribution of Ca²⁺-activated K⁺ channels in SMCs and ECs from a single arterial site.     

Conversion of a gene-specific repressor to a regional silencer

In Saccharomyces cerevisiae, gene silencing at the HMR and HML loci is normally dependent on Sir2p, Sir3p, and Sir4p, which are structural components of silenced chromatin. Sir2p is a NAD+-dependent histone deacetylase required for silencing. Silencing can be restored in cells lacking Sir proteins by a dominant mutation in SUM1, which normally acts as a mitotic repressor of meiotic genes. This study found that mutant Sum1-1p, but not wild-type Sum1p, associated directly with HM loci. The origin recognition complex (ORC) was required for Sum1-1p-mediated silencing, and mutations in ORC genes reduced association of Sum1-1p with the HM loci. Sum1-1p-mediated silencing also depended on HST1, a paralog of SIR2. Both Sum1-1p and wild-type Sum1p interacted with Hst1p in coimmunoprecipitation experiments. Therefore, the SUM1-1 mutation did not change the affinity of Sum1p for Hst1p, but rather relocalized Sum1p to the HM loci. Sum1-1-Hst1p action led to hypoacetylation of the nucleosomes at HM loci. Thus, Sum1-1p and Hst1p could substitute for Sir proteins to achieve silencing through formation of a compositionally distinct type of heterochromatin.     

Staging of malignant pleural mesothelioma: comparison of CT and MR imaging

OBJECTIVE: This article compares the accuracy of CT with that of MR imaging in staging of malignant pleural mesothelioma. SUBJECTS AND METHODS: Ninety-five patients were enrolled in a prospective staging protocol based on the International Mesothelioma Interest Group staging system. Sixty-five patients underwent CT and MR imaging and a surgical procedure (excluding percutaneous needle biopsy) to stage and resect the tumor. Receiver operating characteristic analyses were performed. CT and MR scans were interpreted independently by observers who were unaware of the results of the other imaging study; these imaging findings were compared with the results of surgery and pathologic examination. RESULTS: The areas under the receiver operating characteristic curves for eight of 10 features revealed by imaging showed no statistically significant differences between CT and MR imaging. However, MR imaging was superior to CT in revealing invasion of the diaphragm (A(z) = .55 for CT versus .82 for MR imaging) and in revealing invasion of endothoracic fascia or solitary resectable foci of chest wall invasion (A(z) = .46 for CT; A(z) = .69 for MR imaging). Several anatomic regions could not be evaluated because positive findings at surgery were rare. CONCLUSION: CT and MR imaging are of nearly equivalent diagnostic accuracy in staging malignant pleural mesothelioma. MR imaging is superior to CT in revealing solitary foci of chest wall invasion and endothoracic fascia involvement and in showing diaphragmatic muscle invasion; however, this advantage does not affect surgical treatment. For cost reasons, CT should be considered the standard diagnostic study before therapy.     

Homozygous deletion of CDKN2A and codeletion of the methylthioadenosine phosphorylase gene in the majority of pleural mesotheliomas.

PURPOSE: Homozygous deletions at chromosome region 9p21 targeting the CDKN2A gene have been reported as a common cytogenetic abnormality in mesothelioma. MTAP, a gene approximately 100-kb telomeric to CDKN2A, encodes methylthioadenosine phosphorylase, an enzyme essential in the salvage of cellular adenine and methionine, and its codeletion with CDKN2A has been reported in other tumors. The aim of this study was to define the prevalence of homozygous deletion of CDKN2A alone or in combination with MTAP in a large series of pleural mesothelioma. EXPERIMENTAL DESIGN: We used a fluorescent in situ hybridization assay for CDKN2A and MTAP on interphase nuclei in imprints of frozen tissue from 95 cases of pleural mesothelioma. Histologically, the cases were classified as epithelial (71), biphasic (19) and sarcomatous (5). In each experiment, a 9p21 locus specific probe and a chromosome 9 centromeric probe were used and fluorescent in situ hybridization signals for both probes were simultaneously recorded in at least 100 nuclei. Cases were considered homozygously deleted if both 9p21 signals were lost in at least 20% of nuclei. RESULTS: Overall, 70 cases (74%) had homozygous deletion of CDKN2A. MTAP was codeleted in 64 of these cases (91%). No case with MTAP deletion without CDKN2A deletion was identified. Homozygous loss of CDKN2A was seen in 49 of 71 epithelial (70%), 16 of 19 biphasic (89%), and 5 of 5 sarcomatous (100%) mesotheliomas. CONCLUSIONS: Homozygous deletion of CDKN2A is seen in the majority of pleural mesotheliomas, and MTAP is codeleted in most of these cases. Previous cell line studies have shown that loss of MTAP renders cells dependent on de novo synthesis of purine derivatives. Thus, the particularly high prevalence of MTAP codeletion in mesothelioma makes it an ideal candidate for trials of targeted therapy using inhibitors of de novo AMP synthesis (e.g., L-alanosine).     

Whole body 18FDG-PET and the response of esophageal cancer to induction therapy: results of a prospective trial.

PURPOSE: Whole-body 18F-fluorodeoxyglucose ([18F]FDG) positron emission tomography (PET) imaging before and after induction therapy was prospectively evaluated in patients with esophageal cancer to determine whether changes in PET images could measure response to therapy. PATIENTS AND METHODS: Between April 1997 and April 1999, 39 patients (34 men and five women; median age, 59 years; range, 36 to 76 years) with esophageal cancer were prospectively enrolled in a single-institution clinical trial of staging, including PET, induction therapy, restaging including PET, and esophagectomy. All patients undergoing esophagectomy after induction therapy (n = 17) were followed either to recurrence, to death, or through a disease-free interval of at least 24 months. RESULTS: PET after standard staging studies and before therapy imaged undetected sites of metastatic disease in six patients (15%). Restaging (including PET) after induction therapy did not identify any patients with disease progression or any patients with loco-regionally unresectable disease at exploration. The median decrease in the standardized uptake value (SUV) during induction therapy was 59%. After R0 esophagectomy, the 2-year disease-free and overall survival was 38% and 63%, respectively, among patients who had a less than 60% decrease in SUV, and 67% and 89%, respectively, among patients who had a greater than 60% decrease in SUV (P =.055 and P =.088, respectively). CONCLUSION: Compared with conventional imaging, PET detects additional sites of metastatic disease at initial evaluation. After induction therapy, PET did not add to the estimation of loco-regional resectability and did not detect new distant metastases. However, changes in [18F]FDG PET may predict disease-free and overall survival after induction therapy and resection in patients with esophageal cancer. Further evaluation in larger trials is warranted.