Idiopathic Interstitial Pneumonia with Increased Serum Levels of Cancer-Associated Antigens, CA19-9 and SLX

We report a case of idiopathic interstitial pneumonia (IIP) with elevated serum levels of carbohydrate antigen 19-9 (CA19-9) and sialyl Lewisx-i (SLX). A 67-year-old Japanese woman was admitted to our hospital with a fever, dry cough and dyspnea on exertion. She had previously been admitted and had then been diagnosed as IIP. The serum level of SLX, measured by radioimmunoassay (RIA), was markedly elevated (120 U/mL; cut-off, < 38 U/mL). The serum level of CA19-9, measured by RIA, was at a slightly high level (46 U/mL; cut-off, < 40 U/mL). The values of CA19-9 and SLX were changed during her clinical course. These cancer-associated antigens were immunohistochemically expressed on the hyperplastic bronchiolar epithelium, on the surface epithelium cells of microscopic honeycombing and on exudates in air space. Repeated damage to the lungs may have forced these antigens of the markers into the blood circulation, which may have resulted in the elevated serum levels of CA19-9 and SLX observed in this patient

Polymorphic mutations in mouse mitochondrial DNA regulate a tumor phenotype

To examine whether polymorphic mtDNA mutations that do not induce significant respiration defects regulate phenotypes of tumor cells, we used mouse transmitochondrial tumor cells (cybrids) with nuclear DNA from C57BL/6 (B6) strain and mtDNA from allogenic C3H strain. The results showed that polymorphic mutations of C3H mtDNA in the cybrids induced hypoxia sensitivity, resulting in a delay of tumor formation on their subcutaneous inoculation into B6 mice. Therefore, the effects of polymorphic mutations in normal mtDNA have to be carefully considered, particularly when we apply the gene therapy to the embryos to replace their pathogenic mtDNA by normal mtDNA

The innate immune system in host mice targets cells with allogenic mitochondrial DNA

Tumors or embryonic stem cells bearing foreign mitochondrial DNA are rejected by the innate immune system via a mechanism that depends on MyD88

Aclarubicin in the treatment of elderly patients with acute nonlymphocytic leukemia.

Thirteen previously untreated patients aged 70 and above with acute nonlymphocytic leukemia were treated with aclarubicin (ACR) alone. Among 10 cases (3, acute myelocytic leukemia; 4, acute myelomonocytic leukemia; 2, acute monocytic leukemia; and one, acute erythroleukemia) in which an evaluation was possible, 5 cases (3, acute myelomonocytic leukemia; and 2, acute monocytic leukemia) obtained complete remission (CR). The CR rate was 83% in 6 patients with acute myelomonocytic leukemia or acute monocytic leukemia. The median CR duration and survival was 7.5 and 10 + months, respectively. Although side effects of the drug on digestive system such as nausea, vomiting and anorexia were observed in all patients, they were controllable by conventional treatments. The results suggest that ACR is effective for the clinical management of elderly patients with acute nonlymphocytic leukemia, especially those with acute myelomonocytic leukemia or acute monocytic leukemia.</p

CRISPR-Cas3 induces broad and unidirectional genome editing in human cells

Although single-component Class 2 CRISPR systems, such as type II Cas9 or type V Cas12a (Cpf1), are widely used for genome editing in eukaryotic cells, the application of multi-component Class 1 CRISPR has been less developed. Here we demonstrate that type I-E CRISPR mediates distinct DNA cleavage activity in human cells. Notably, Cas3, which possesses helicase and nuclease activity, predominantly triggered several thousand base pair deletions upstream of the 5′-ARG protospacer adjacent motif (PAM), without prominent off-target activity. This Cas3-mediated directional and broad DNA degradation can be used to introduce functional gene knockouts and knock-ins. As an example of potential therapeutic applications, we show Cas3-mediated exon-skipping of the Duchenne muscular dystrophy (DMD) gene in patient-induced pluripotent stem cells (iPSCs). These findings broaden our understanding of the Class 1 CRISPR system, which may serve as a unique genome editing tool in eukaryotic cells distinct from the Class 2 CRISPR system