Lung cancer: is there a place for elective nodal irradiation?]

The use of conformal radiotherapy in lung cancer has considerably evolved with the advent of improved staging technologies and methods of radiation delivery. Patients with limited disease, inoperable for medical reasons, may be treated with conformal radiotherapy alone; patients with more advanced disease are treated with combined chemo-radiotherapy. If local control may be improved by radiotherapy dose escalation according to several studies, toxicity and more particularly pulmonary toxicity seems to be related to radiation volume. Thus the use of elective nodal irradiation is being questioned. Data for early stage (stage I) non-small-cell lung cancer treated with conformal radiotherapy or stereotactic hypofractionated radiotherapy strongly supports the use of smaller fields that do not incorporate elective nodal regions; local control and survival rates approach those of surgical series. In locally advanced non-small cell lung cancer, eliminating elective nodal irradiation allows to maximize tumor dose and minimize normal tissue toxicity in combined modality treatments; results are encouraging. The use of staging modalities such as positron emission tomography and eventually oesophageal ultrasonography is increasing, allowing to encompass the tumor volume with more accuracy. Several studies have confirmed that involved-field irradiation results into a regional nodal rate of less than 10%. Further larger-scale studies would be needed to definitely establish "no elective nodal irradiation" as a standard in non-small cell lung cancer. There are very few data concerning small cell lung cancer.     

LIGHT induces differentiation of mouse embryonic stem cells associated with activation of ERK5

LT-related inducible ligand that competes for glycoprotein D binding to herpesvirus entry mediator on T cells (LIGHT) is a recently cloned type II transmembrane protein belonging to the TNF family that was originally identified as a weak inducer of apoptosis. This cytokine has been extensively defined in its role on T-cell regulation and dendritic cell maturation. However, whether this cytokine regulates stem cell proliferation and/or differentiation remains unknown. In this study, we transduced exogenous LIGHT into embryonic stem cells (ES cells) and found it induced their differentiation. The expression of phospho-STAT3, Nanog and Oct-4 was reduced in LIGHT-transduced ES cells compared with wild-type ES cells. LIGHT-transduced ES cells exhibit a low level of SSEA-1 surface antigen and alkaline phosphatase staining compared with wild-type cells. Introduction of LIGHT into ES cells results in the dephosphorylation of MKP-3 and activation of extracellular signal-regulated kinase (ERK)5. When ERK5 was inhibited by the specific inhibitor PD184352 or knocked down by ERK5 siRNA, reduction of Oct-4 and SSEA-1 expression was rescued. We conclude that LIGHT overrides Leukemia inhibitory factor to induce ES cell differentiation associated with activation of ERK5.     

Evolutionary relationship between Old World West Nile virus strains. Evidence for viral gene flow between Africa, the Middle East, and Europe

Little is known about the genetic relationships between European and other Old-World strains of West Nile virus (WNV) and persistence of WNV North of Mediterranean. We characterized the complete genomes of three WNV strains from France (horse-2000), Tunisia (human-1997) and Kenya (mosquito-1998), and the envelope, NS3 and NS5 genes of the Koutango virus. Phylogenetic analyses including all available full-length sequences showed that: (1) Koutango virus is a distant variant of WNV; (2) the three characterized strains belong to lineage 1, clade 1a; (3) the Tunisian strain roots the lineage of viruses introduced in North America. We established that currently available partial envelope sequences do not generate reliable phylogenies. Accordingly, establishing a large WNV sequence database is pivotal for the understanding of spatial and temporal epidemiology of this virus. For rapid completion of that purpose, colinearized E-NS3-NS5 gene sequences were shown to constitute a valuable surrogate for complete sequences.     

Postoperative cell mediated immune response is better preserved after laparoscopic vs open colorectal resection in humans

BACKGROUND: Animal studies have documented significantly better preserved postoperative cell-mediated immune function, as measured by serial delayed-type hypersensitivity (DTH) challenges, after laparoscopic-assisted than after open bowel resection. Similarly, in humans, the DTH responses after open cholecystectomy have been shown to be significantly smaller than preoperative responses; whereas after laparoscopic cholecystectomy, no significant change in DTH response has been noted. The purpose of this study was to assess cell-mediated immune function via serial DTH skin testing in patients undergoing laparoscopic or open colectomy. METHODS: A total of 35 subjects underwent either laparoscopic (n = 18) or open colectomy (n = 17) in this prospective but not randomized study. Only patients who were judged to be immunoresponsive by virtue of having responded successfully to a preoperative DTH challenge were eligible for entry in the study. DTH challenges were carried out at three time points in all patients: preoperatively, immediately following surgery, and on the third postoperative day (POD 3). Responses were measured 48 h after each challenge and the area of induration calculated. There were no significant differences between the laparoscopic (LC) and open (OC) colorectal resection groups in regard to demographics, indications for surgery, or type of resection carried out. The percentage of patients transfused was similar in both groups (17%, LC; 12% OC; p = NS). In the LC group, all cases were completed without conversion using minimally invasive methods. There were no perioperative deaths, and the rate of postoperative complications was similar in both groups. The preoperative and postoperative DTH results were analyzed and compared within each surgical group using several methods. RESULTS: In regards to the OC group results, the median sum-total DTH responses for the day of surgery challenges (0.44 +/- 69 cm2) and the POD 3 challenges (0.72 +/- 3.37 cm2) were significantly smaller than the preoperative results (3.61 +/- 3.83 cm2, p <0.0005 vs op day and p <0.0003 vs POD 3 results). When the LC group results were similarly analyzed, no significant difference in DTH response was noted between the pre- and the postoperative challenge results. Additionally, when the median percent change from baseline was calculated and considered for the OC group's DTH results, both postoperative challenge time points demonstrated significantly decreased responses when compared to their preoperative results (vs day of surgery, p <0.007; vs POD 3, p <0.006). Similar analysis of the LC group's results yielded nonsignificant differences between the pre- and postoperative responses. Lastly, when the LC and the OC groups median percent change from baseline results were directly compared for each of the postoperative challenges, a significant difference was noted for the POD 0 challenge (LC, -21%; OC 88%; p <0.004) but not for the POD 3 challenge. CONCLUSIONS: The postoperative DTH responses of the open surgery patients were significantly smaller than their preoperative responses. This was not the case for the laparoscopic group (a combination of fully laparoscopic and laparoscopic-assisted resections). When the open and laparoscopic groups results are directly compared, regarding the results of the day of surgery DTH challenges, the LC groups median percent change from baseline was significantly less than that observed in the OC group. These results imply that open colorectal resection is associated with a significant suppression of cell-mediated immune response postoperatively, whereas in this study laparoscopic colorectal resection was not. Further human studies are needed to verify these findings and to determine the clinical significance, if any, of this temporary difference in immune function following colon resection.