BackgroundMesothelioma is resistant to conventional treatments and is often defective in p53 pathways. We then examined anti-tumor effects of metformin, an agent for type 2 diabetes, and combinatory effects of metformin and nutlin-3a, an inhibitor for ubiquitin-mediated p53 degradation, on human mesothelioma.MethodsWe examined the effects with a colorimetric assay and cell cycle analyses, and investigated molecular events in cells treated with metformin and/or nutlin-3a with Western blot analyses. An involvement of p53 was tested with siRNA for p53.ResultsMetformin suppressed cell growth of 9 kinds of mesothelioma including immortalized cells of mesothelium origin irrespective of the p53 functional status, whereas susceptibility to nutlin-3a was partly dependent on the p53 genotype. We investigated combinatory effects of metformin and nutlin-3a on, nutlin-3a sensitive MSTO-211H and NCI-H28 cells and insensitive EHMES-10 cells, all of which had the wild-type p53 gene. Knockdown of p53 expression with the siRNA demonstrated that susceptibility of MSTO-211H and NCI-H28 cells to nutlin-3a was p53-dependent, whereas that of EHMES-10 cells was not. Nevertheless, all the cells treated with both agents produced additive or synergistic growth inhibitory effects. Cell cycle analyses also showed that the combination increased sub-G1 fractions greater than metformin or nutlin-3a alone in MSTO-211H and EHMES-10 cells. Western blot analyses showed that metformin inhibited downstream pathways of the mammalian target of rapamycin (mTOR) but did not activate the p53 pathways, whereas nutlin-3a phosphorylated p53 and suppressed mTOR pathways. Cleaved caspase-3 and conversion of LC3A/B were also detected but it was dependent on cells and treatments. The combination of both agents in MSTO-211H cells rather suppressed the p53 pathways that were activated by nutrin-3a treatments, whereas the combination rather augmented the p53 actions in NCI-H28 and EHMES-10 cells.ConclusionThese data collectively indicated a possible interactions between mTOR and p53 pathways, and the combinatory effects were attributable to differential mechanisms induced by a cross-talk between the pathways.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3300-y) contains supplementary material, which is available to authorized users.

The muscle volume analyzer (MVA) can predict limb muscle weight based on bioelectric impedance analysis, whereas the conventional handheld dynamometer (HHD) measures muscle strength. In this study, a 26-year-old female on invasive ventilation due to late-onset Pompe disease was treated with enzyme replacement therapy (ERT) for 12 months. MVA measurements demonstrated time-dependent improvement from the baseline compared to HHD measurements, showing remarkably fluctuating muscle strength. Thus, the MVA can be used as an alternative, particularly for patients suffering from severe limb muscle weakness.

Acupuncture needles can cause non‐tuberculosis mycobacteria (NTM) infection on the skin, but there are no reports that acupuncture needles inserted into the lung have caused lung NTM infection. A 63‐year‐old woman, who underwent removal of a broken acupuncture needle inserted into the lung nine years ago, was admitted with nodules in the right lung. The shadow was positioned where the needle had existed. Partial lung resection of the right lower lobe was performed, and the resected area showed caseous necrosis histopathologically. Furthermore, Mycobacterium avium was cultured from the specimen. When abnormal lung shadows are located where a resected foreign body appeared, NTM infection should be considered.

Shoyogan is a Kampo prescription described in the Junqui Yaolue. Few cases have been reported using this medicine. This time, we prescribed shoyogan for 14 patients who suffered from severe appetite loss. We had positive outcomes as follows. We administered shoyogan to 8 patients with malignant disease. Six of them suffered from lung cancer. Shoyogan was effective in these patients. Shoyogan was not effective for the other 2 patients, with bile duct carcinoma and malignant lymphoma. The dietary intake was increased from 28 percent of meals supplied to 79 percent in the appetite-improved group. We also administered shoyogan to 6 patients with nonmalignant disease. It was effective for 3 patients : 1 with congestive heart failure and 2 with great trochanteric fractures of the femur. It was not effective for the other 3 patients, who suffered from anorexia, pneumonia and depression associated with diabetes mellitus. Shoyogan seems to be effective for patients with terminal lung cancer and maintains their quality of life. appetite, lung cancer, shoyogan, QOL

Partial anomalous pulmonary venous return (PAPVR) is a rare congenital cardiovascular anomaly. A 68-year-old woman was referred to our hospital for detailed examination for pulmonary hypertension (PH). She had been diagnosed as having pulmonary artery dilation and suspected to have PH during a health check seven years prior. A contrast computed tomography showed that the right upper pulmonary vein (RUPV) returned to the superior vena cava (SVC) with a preserved normal connection to the left atrium (LA). Surgical repair was performed. We reported an extremely rare case of isolated PAPVR with PH showing dual drainage into the SVC and LA.