Cell Cycle Regulation via the p53, PTEN, and BRCA1 Tumor Suppressors

Multiple cell cycle regulatory proteins play an important role in oncogenesis. Cancer cells may arise from dysregulation of various genes involved in the regulation of the cell cycle. In addition, cyclin-dependent kinase inhibitors are regarded as key regulators for cancer cell proliferation. Accordingly, permission of impaired cells by cell cycle checkpoints suppresses carcinogenesis. P53, a multifunctional protein, controls G1-S transition, which is the strongest tumor suppressor involved in the regulation of cell cycle. The p53 is stimulated by cellular stress like oxidative stress. Upon activation, p53 leads to cell cycle arrest and promotes DNA repair; otherwise, it induces apoptosis. One of the target effectors of p53 is the phosphatase and tensin homolog deleted on chromosome 10 (PTEN). The tumor suppressor PTEN is a dual-specificity phosphatase which has protein phosphatase activity and lipid phosphatase activity that antagonizes PI3K/AKT activity. The PI3K/AKT cell survival pathway is shown as regulator of cell proliferation. The p53 cooperates with PTEN and might be an essential barrier in development of cancers. BRCA1 plays an important role in DNA repair processes related to maintenance of genomic integrity and control of cell growth. The inactivation of these tumor suppressor proteins confers a growth advantage of cancer. This chapter summarizes the function of several tumor suppressors in the cell cycle regulation

Effect of controlled ventilation on diaphragm

Background : Since diaphragm passivity induces oxidative stress that leads to rapid atrophy of diaphragm, we investigated the effect of controlled ventilation on diaphragm thickness during assist-control ventilation (ACV). Methods : Previously, we measured end-expiratory diaphragm thickness (Tdiee) of patients mechanically ventilated for more than 48 hours on days 1, 3, 5 and 7 after the start of ventilation. We retrospectively investigated the proportion of controlled ventilation during the initial 48-hour ACV (CV48%). Patients were classified according to CV48% : Low group, less than 25% ; High group, higher than 25%. Results : Of 56 patients under pressure-control ACV, Tdiee increased more than 10% in 6 patients (11%), unchanged in 8 patients (14%) and decreased more than 10% in 42 patients (75%). During the first week of ventilation, Tdiee decreased in both groups : Low (difference, -7.4% ; 95% confidence interval [CI], -10.1% to -4.6% ; p < 0.001) and High group (difference, -5.2% ; 95% CI, -8.5% to -2.0% ; p = 0.049). Maximum Tdiee variation from baseline did not differ between Low (-15.8% ; interquartile range [IQR], -22.3 to -1.5) and High group (-16.7% ; IQR, -22.6 to -11.1, p = 0.676). Conclusions : During ACV, maximum variation in Tdiee was not associated with proportion of controlled ventilation higher than 25%

Multidisciplinary treatment system for bone metastases for early diagnosis, treatment and prevention of malignant spinal cord compression

Malignant spinal cord compression (MSCC) is a serious complication of cancers. The present study aimed to establish a multidisciplinary treatment system for urgent magnetic resonance imaging (MRI) and referral to orthopedists in order to prevent neurological deficits caused by MSCC. In the present study, the extent to which this system achieved early diagnosis and treatment and prevented MSCC‑caused neurological deficits was examined. The records from patients with neurological deficits caused by MSCC before (between April 2007 and March 2012; group A) and after (between April 2012 and March 2017; group B) the establishment of the multidisciplinary system at the Shikoku Cancer Center (Ehime, Japan) were retrospectively evaluated. The numbers of patients with neurological deficits were 38 and 7 in groups A and B, respectively. All patients received radiotherapy. The incidence of neurological deficits was 13.2 and 3.4% in groups A and B, respectively (P<0.001). The proportion of patients with improvement in the severity of neurological deficits was 5.3 and 28.6% in groups A and B, respectively (P<0.001). The interval between physicians' recognition of a neurological deficit and MRI and the start of treatment, the number of cases, and the severity of neurological deficits were evaluated in groups A and B. The median interval between recognition of a neurological deficit by physicians and MRI was 3 and 0 days in groups A and B, respectively (P<0.001). The median interval between physicians' recognition of a neurological deficit and the start of treatment was 3 and 0 days in groups A and B, respectively (P<0.001). By using a multidisciplinary treatment system, the incidence and severity of neurological deficits following treatment were significantly improved. Therefore, the multidisciplinary treatment system used in the present study may be useful for early diagnosis, treatment and prevention of MSCC in patients with bone metastases

Oxidation behaviour of lattice oxygen in Li-rich manganese-based layered oxide studied by hard X-ray photoelectron spectroscopy

The oxidation/reduction behaviours of lattice oxygen and transition metals in a Li-rich manganese-based layered oxide Li[Li0.25Ni0.20Mn0.55]O1.93 are investigated by using hard X-ray photoelectron spectroscopy (HAX-PES). By making use of its deeper probing depth rather than in-house XPS analyses, we clearly confirm the formation of O- ions as bulk oxygen species in the active material. They are formed on the 1st charging process as a charge compensation mechanism for delithiation and decrease on discharging. In particular, the cation-anion dual charge compensation involving Ni and O ions is suggested during the voltage slope region of the charging process. The Ni ions in the material are considered to increase the capacity delivered by a reversible anion redox reaction with the suppression of O2 gas release. On the other hand, we found structural deterioration in the cycled material. The O- species are still observed but are electrochemically inactive during the 5th charge-discharge cycle. Also, the oxidation state of Ni ions is divalent and inactive, although that of Mn ions changes reversibly. We believe that this is associated with the structural rearrangement occurring after the activation process during the 1st charging, leading to the formation of spinel- or rocksalt-like domains over the sub-surface region of the particles

Dusty ERO Search behind Two Massive Clusters

We performed deep K'-band imaging observations of 2 massive clusters, MS 0451.6-0305 at z = 0.55 and MS 0440.5+0204 at z = 0.19, for searching counterparts of the faint sub-mm sources behind these clusters, which would provide one of the deepest extremely red object(ERO) samples. Comparing our near-infrared images with optical images taken by the Hubble Space Telescope and by the Subaru Telescope, we identified 13 EROs in these fields. The sky distributions of EROs are consistent with the previous results, that there is a sign of strong clustering among detected EROs. Also, the surface density with corrected lensing amplification factors in both clusters are in good agreement with that derived from previous surveys. We found 7 EROs and 3 additional very red objects in a small area (\sim 0.6 arcmin^2) of the MS 0451.6-0305 field around an extended SCUBA source. Many of their optical and near-infrared colors are consistent with dusty star-forming galaxies at high redshifts(z \sim 1.0-4.0), and they may be constituting a cluster of dusty starburst galaxies and/or lensed star-forming galaxies at high redshift. Their red J-K' colors and faint optical magnitudes suggest they are relatively old massive stellar systems with ages(>300 Mega years) suffering from dust obscuration. We also found a surface-density enhancement of EROs around the SCUBA source in the MS 0440.5+0204 field.Comment: 19 pages, 11 figures, Latex(using pasj00.cls). To be published in PASJ vol 55, No. 4(Aug 2003

On-Orbit Demonstration of Innovative Multifunctional Membrane Structure for Ultra-Lightweight Solar Arrays and Array Antennas by 3U CubeSat OrigamiSat-1

The 3U CubeSat OrigamiSat-1’s deployable membrane structure is 1m-by-1m in size after deployment and is stowed in less than 1U CubeSat (10cm-by-10cm-by-8cm), including a hold-and-release mechanism. The major significance of the structural concept is that it allows the attachment of thin-film devices, such as thin-film solar cells or flexible substrates for antennas throughout the membrane. This was achieved by two features: (i) use of textile and (ii) invention of hybrid boom made of tubular carbon composite and metal convex tape. In addition, a visual membrane measurement system consisting of stereo cameras was developed. This paper describes the new technologies developed for this CubeSat