Pulmonary resection for patients with lung cancer with interstitial lung diseases may provoke acute exacerbation at a substantially high rate and has high associated mortality. Surgical procedures that proved to be a risk factor for acute exacerbation should be chosen cautiously for these high-risk patients.

Loss of pulp due to caries and pulpitis leads to loss of teeth and reduced quality of life. Thus, there is an unmet need for regeneration of pulp. A promising approach is stem cell therapy. Autologous pulp stem/progenitor (CD105(+)) cells were transplanted into a root canal with stromal cell-derived factor-1 (SDF-1) after pulpectomy in mature teeth with complete apical closure in dogs. The root canal was successfully filled with regenerated pulp including nerves and vasculature by day 14, followed by new dentin formation along the dentinal wall. The newly regenerated tissue was significantly larger in the transplantation of pulp CD105(+) cells with SDF-1 compared with those of adipose CD105(+) cells with SDF-1 or unfractionated total pulp cells with SDF-1. The pulp CD105(+) cells highly expressed angiogenic/neurotrophic factors compared with other cells and localized in the vicinity of newly formed capillaries after transplantation, demonstrating its potent trophic effects on neovascularization. Two-dimensional electrophoretic analyses and real-time reverse transcription-polymerase chain reaction analyses demonstrated that the qualitative and quantitative protein and mRNA expression patterns of the regenerated pulp were similar to those of normal pulp. Thus, this novel stem cell therapy is the first demonstration of complete pulp regeneration, implying novel treatment to preserve and save teeth.

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The gene(s) responsible for natural killer (NK)-cell lymphoma/leukemia have not been identified. In the present study, we found that in NK-cell lymphoma lines (n ‫؍‬ 10) and specimens of primary lymphoma (n ‫؍‬ 10), levels of miR-21 and miR-155 expression were inversely related and were significantly greater than those found in normal natural killer (CD3 ؊ CD56 ؉ ) cells (n ‫؍‬ 8). To determine the functions of these microRNAs in lymphomagenesis, we examined the effects of antisense oligonucleotides (ASOs) tar- IntroductionNatural killer (NK)-cell lymphomas/leukemias are characterized groups of highly aggressive lymphoid malignancies, which are composed of "extranodal NK/T-cell lymphoma, nasal type" and "aggressive NK-cell leukemia." 1 Notably, these 2 subtypes show many similarities in their morphologic features, immunophenotypes, and genotypes and are invariably associated with EpsteinBarr virus (EBV), which suggests they may share the same genetic alterations. To assign a classification, the World Health Organization classification uses cytogenetic and molecular features to characterize lymphoma subtypes. 1 For example, it is known that various genomic translocations and genetic alterations, including BCL2, CCDN1, and c-MYC, occur in B-cell lymphomas. These disease-specific genetic translocations characterize lymphoma subtypes, such as follicular lymphoma characterized by BCL2 rearrangement, mantle-cell lymphoma characterized by CCDN1 rearrangement, and Burkitt lymphoma characterized by c-MYC rearrangement. However, although the World Health Organization classification recognizes NK-cell lymphomas/leukemias as distinct clinicopathologic entities, disease-specific translocations and the gene(s) affected in the 2 subtypes have not yet been identified. It was previously reported that a 6q deletion occurs in approximately 10% to 20% of NK-cell lymphomas/leukemias 2-7 ; however, this loss may not be disease specific because it has been observed in a variety of cancers, including solid tumors and hematologic malignancies. It is currently unclear whether the loss is a primary or progression-associated event.It was recently discovered that some microRNAs (miRNAs) are oncogenic in B-cell lymphomas. For example, aberrant overexpression of 2 miRNAs, miR-17-92 and miR-155, is closely associated with B-cell lymphomagenesis. 8 With respect to miR-17-92, we recently demonstrated that the polycistron can down-regulate CDKN1A/p21 in B-cell lymphomagenesis and promote cell-cycle regulation. 8 Furthermore, it is unlikely that aberrant expression of miRNAs is restricted to B-cell lymphomas, and it may occur in other lymphoma subtypes, including T/NK-cell lymphomas. In the present study, therefore, we used Northern and quantitative polymerase chain reaction (PCR) analyses to screen for and quantitatively assess miRNA expression in NK-cell lymphomas/leukemias and found that miR-21 and miR-155 were overexpressed in NK-cell lymphoma/leukemia. Moreover, the effects of antisense oligonucleotides (ASOs) revealed that miR-21 and miR-15...

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MicroRNA (miRNA; miR) is a class of small regulatory RNA molecules, the aberrant expression of which can lead to the development of cancer. We recently reported that overexpression of miR-21 and/or miR-155 leads to activation of the phosphoinositide 3-kinase (PI3K)-AKT pathway in malignant lymphomas expressing CD3 À CD56þ natural killer (NK) cell antigen. Through expression analysis, we show in this study that in both NK/T-cell lymphoma lines and samples of primary lymphoma, levels of miR-150 expression are significantly lower than in normal NK cells. To examine its role in lymphomagenesis, we transduced miR-150 into NK/T-cell lymphoma cells, which increased the incidence of apoptosis and reduced cell proliferation. Moreover, the miR-150 transductants appeared senescent and showed lower telomerase activity, resulting in shortened telomeric DNA. We also found that miR-150 directly downregulated expression of DKC1 and AKT2, reduced levels of phosphorylated AKT ser473/4 and increased levels of tumor suppressors such as Bim and p53. Collectively, these results suggest that miR-150 functions as a tumor suppressor, and that its aberrant downregulation induces continuous activation of the PI3K-AKT pathway, leading to telomerase activation and immortalization of cancer cells. These findings provide new insight into the pathogenesis of malignant lymphoma.

Intraneuronal accumulation of paired helical filaments (PHF) is considered to be closely related to the neuronal loss observed in brains of patients affected with Alzheimer's disease. The central issue is whether PHF formation itself causes or accelerates the neuronal perikaryal and neuritic degeneration or whether they are simply the consequence of preceding degeneration. We sought to address the issue in part by characterizing the PHF-associated molecules and thus raised a number of monoclonal antibodies to neurofibrillary tangles. One monoclonal antibody, 3F4, strongly reacted with neurofibrillary tangles and some plaque neurites but few neuropil threads. This monoclonal antibody labeled a 65-kDa protein, but not tau or ubiquitin, on a Western blot of human brain extract and immunoprecipitated the same protein. The peptides released from the purified 65-kDa protein had the same sequences as those of a newly identified protein, human collapsin response mediator protein-2. Incorporation into neurofibrillary tangles may deplete soluble, cytosolic human collapsin response mediator protein-2 and lead to abnormal neuritic and/or axonal outgrowth of the tangle-bearing neuron, thus accelerating the neuritic degeneration in Alzheimer's disease.

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