Human γδ T cells can recognize and kill non-small cell lung cancer (NSCLC) cells using the Vγ9Vδ2 T-cell receptor and/or NKG2D. We have established clinical grade large-scale ex vivo expansion of γδ T cells from peripheral blood mononuclear cells by culturing with zoledronate and interleukin-2 (IL-2). A phase I study was conducted to evaluate safety and potential antitumor effects of re-infusing ex vivo expanded γδ T cells in patients with recurrent or advanced NSCLC. Patient's peripheral blood mononuclear cells were stimulated with zoledronate (5 μM) and IL-2 (1000 IU/mL) for 14 days. Harvested cells, mostly γδ T cells, were given intravenously every 2 weeks without additional IL-2, a total of 6 times. The cumulative number of transferred γδ T cells ranged from 2.6 to 45.1 x 10⁹ (median, 15.7×10⁹). Fifteen patients underwent adoptive immunotherapy with these γδ T cells. There were no severe adverse events related to the therapy. Immunomonitoring data showed that with increasing numbers of infusions, the number of peripheral γδ T cells gradually increased. All patients remained alive during the study period with a median survival of 589 days and median progression-free survival of 126 days. According to the Response Evaluation Criteria In Solid Tumors, there were no objective responses. Six patients had stable disease, whereas the remaining 6 evaluable patients experienced progressive disease 4 weeks after the sixth transfer. We conclude that adoptive transfer of zoledronate-expanded γδ T cells is safe and feasible in patients with NSCLC, refractory to other treatments.

No abstract

The structure of the retina, the distribution of ganglion cells, and the extent of the tapetum lucidum were studied in Dall's porpoise (Phocoenoides dalli) with the aim of understanding the role vision plays in this species of cetacean. The basic organization of the retina was similar to that of other vertebrates. Average ganglion cell size was 2 1.5 hm. The distribution of the ganglion cells in the retina was not even and there were two high-density areas, one in the temporal and one in the rostra1 part of the retina. Retinal resolving power was estimated using a terrestrial animal model incorporating the density of ganglion cells and other morphological data. The resolving power in the right eyes of two individuals was 2.60 and 2.64 cycles per degree. These values were close to those of other oceanic cetaceans, but inferior to those of terrestrial mammals. On the basis of amino acid analyses, it was shown that the choroid tapetum lucidum in Dali's porpoise contained collagen. The tapetum lucidum was thick at the fundal but thin at the peripheral part of the choroid.

The GPS is a useful prognostic indicator of the OS in lung cancer surgery. The optimal cut-off values for GPS estimation may need to be re-evaluated.

Pulmonary metastasectomy for HCC in selected patients resulted in relatively good outcomes with regard to OS. History of recurrence and serum DCP levels were shown to be candidates of prognostic factors for OS.

Thoracoscopic segmentectomy for the posterior basal segment (S10) and its variant (e.g., S9+10 and S10b+c combined subsegmentectomy) is one of the most challenging anatomical segmentectomies.Stapler-based segmentectomy is attractive to simplify the operation and to prevent post-operative air leakage.However, this approach makes thoracoscopic S10 segmentectomy even more tricky. The challenges are caused mostly from the following three reasons: first, similar to other basal segments, "three-dimensional" stapling is needed to fold a cuboidal segment; second, the belonging pulmonary artery is not directly facing the interlobar fissure or the hilum, making identification of target artery difficult; third, the anatomy of S10 and adjacent segments such as superior (S6) and medial basal (S7) is variable. To overcome these challenges, this article summarizes the "bidirectional approach" that allows for solid confirmation of anatomy while avoiding separation of S6 and the basal segment. To assist this approach under limited thoracoscopic view, we also show stapling techniques to fold the cuboidal segment with the aid of "standing stiches". Attention should also be paid to the anatomy of adjacent segments particularly that of S7, which tends to be congested after stapling. The use of virtual-assisted lung mapping (VAL-MAP) is also recommended to demark resection lines because it flexibly allows for complex procedures such as combined subsegmentectomy such as S10b+c, extended segmentectomy such as S10+S9b, and non-anatomically extended segmentectomy.

No abstract

Morbillivirus infection is a severe threat to marine mammals. Mass die-offs caused by this infection have repeatedly occurred in bottlenose dolphins (Turiops truncatus) and striped dolphins (Stenella coeruleoalba), both of which belong to the family Delphinidae, but not in other cetaceans. However, it is unknown whether sensitivity to the virus varies among cetacean species. The signaling lymphocyte activation molecule (SLAM) is a receptor on host cells that allows morbillivirus invasion and propagation. Its immunoguloblin variable domain-like (V) region provides an interface for the virus hemagglutinin (H) protein. In this study, variations in the amino acid residues of the V region of 26 cetacean species, covering almost all cetacean genera, were examined. Three-dimensional (3D) models of them were generated in a homology model using the crystal structure of the marmoset SLAM and measles virus H protein complex as a template. The 3D models showed 32 amino acid residues on the interface that possibly bind the morbillivirus. Among the cetacean species studied, variations were found at six of the residues. Bottlenose and striped dolphins have substitutions at five positions (E68G, I74V, R90H, V126I, and Q130H) compared with those of baleen whales. Three residues (at positions 68, 90 and 130) were found to alternate electric charges, possibly causing changes in affinity for the virus. This study shows a new approach based on receptor structure for assessing potential vulnerability to viral infection. This method may be useful for assessing the risk of morbillivirus infection in wildlife.