Ataxia-Telangiectasia Mutated and the Mre11-Rad50-NBS1 Complex:Promising Targets for Radiosensitization

Radiotherapy plays a central part in cancer treatment, and use of radiosensitizing agents can greatly enhance this modality. Although studies have shown that several chemotherapeutic agents have the potential to increase the radiosensitivity of tumor cells, investigators have also studied a number of molecularly targeted agents as radiosensitizers in clinical trials based on reasonably promising preclinical data. Recent intense research into the DNA damage-signaling pathway revealed that ataxia-telangiectasia mutated (ATM) and the Mre11-Rad50-NBS1 (MRN) complex play central roles in DNA repair and cell cycle checkpoints and that these molecules are promising targets for radiosensitization. Researchers recently developed three ATM inhibitors (KU-55933, CGK733, and CP466722) and an MRN complex inhibitor (mirin) and showed that they have great potential as radiosensitizers of tumors in preclinical studies. Additionally, we showed that a telomerase-dependent oncolytic adenovirus that we developed (OBP-301 [telomelysin]) produces profound radiosensitizing effects by inhibiting the MRN complex via the adenoviral E1B55kDa protein. A recent Phase I trial in the United States determined that telomelysin was safe and well tolerated in humans, and this agent is about to be tested in combination with radiotherapy in a clinical trial based on intriguing preclinical data demonstrating that telomelysin and ionizing radiation can potentiate each other. In this review, we highlight the great potential of ATM and MRN complex inhibitors, including telomelysin, as radiosensitizing agents

Variations In Volume And Dimensions Of Rays And Their Effect On Wood Properties Of Teak

Six teak (Tectona grandis L.) trees were sampled from two districts in Bangladesh. Ray proportion and dimensions of rays (ray area, ray height, and ray width) on tangential sections were measured, and the influence of ray volume on longitudinal and radial compression strength was investigated. Ray proportion remained more or less constant from pith to bark. Number of rays/mm2 and dimensions of rays became constant at about ring 10 from the pith. Ray proportion and dimensions showed characteristic values from tree to tree and were not affected by growth rate. The trees that had the highest ray volume showed higher specific gravity and higher radial compression strength. It can be considered as the influence of the rays. Hence it may be advisable to breed teak with a high ray proportion

Laparoscopic and Endoscopic Cooperative Surgery for Gastric Submucosal Tumor Near Esophagogastric Junction With Sliding Hiatal Hernia

The usefulness of laparoscopic and endoscopic cooperative surgery (LECS) for gastric submucosal tumors in the cardiac region has been reported in recent years. However, LECS for submucosal tumors at the esophagogastric junction with hiatal sliding esophageal hernia has not been reported, and its validity as a treatment method is unknown. The patient was a 51-year-old man with a growing submucosal tumor in the cardiac region. Surgical resection was indicated because a definitive diagnosis of the tumor was not determined. The lesion was a luminal protrusion tumor, located on the posterior wall of the stomach 20 mm from the esophagogastric junction, and had a maximum diameter of 16.3 mm on endoscopic ultrasound examination. Because of the hiatal hernia, the lesion could not be detected from the gastric side by endoscopy. Local resection was considered to be feasible because the resection line did not extend into the esophageal mucosa and the resection site could be less than half the circumference of the lumen. The submucosal tumor was resected completely and safely by LECS. The tumor was diagnosed as a gastric smooth muscle tumor finally. Nine months after surgery, a follow-up endoscopy showed reflux esophagitis. LECS was a useful technique for submucosal tumors of the cardiac region with hiatal hernia, but fundoplication might be considered for preventing backflow of gastric acid

Did “Kayoinoba” Prevent the Decline of Mental and Physical Functions and Frailty for the Home-Based Elderly during the COVID-19 Pandemic?

The purpose of this study is to grasp the management situation of “Kayoinoba” under the conditions of self-quarantine due to the COVID-19 pandemic. It is also to clarify the efficacy of “Kayoinoba” using the Kihon Checklist (KCL) for the assessment of mental and physical functions in the elderly. The respondents were 136 elderly people aged 65 years and over who lived in A City, a standard rural area in Japan. The age, gender, living style, affluence for living, and the frequency of participation in “Kayoinoba” were examined by using the KCL as a self-completed questionnaire. Finally, 101 respondents were included in the final analysis. There was no difference in the participation status before and after the spread of COVID-19. The frailty ratio tended to decrease from 23.8% to 19.8% between the two periods, but there was no difference in the frailty ratio. It is suggested that the participants in “Kayoinoba” may have suppressed the deterioration of mental and physical conditions, excluding physical activity. This would prevent the frailty of the elderly, even during self-quarantine due to the spread of COVID-19

Precise navigation surgery of tumours in the lung in mouse models enabled by in situ fluorescence labelling with a killer-reporter adenovirus.

BackgroundCurrent methods of image-guided surgery of tumours of the lung mostly rely on CT. A sensitive procedure of selective tumour fluorescence labelling would allow simple and high-resolution visualisation of the tumour for precise surgical navigation.MethodsHuman lung cancer cell lines H460 and A549 were genetically transformed to express red fluorescent protein (RFP). Tumours were grown subcutaneously for each cell line and harvested and minced for surgical orthotopic implantation on the left lung of nude mice. Tumour growth was measured by fluorescence imaging. After the tumours reached 5 mm in diameter, they were injected under fluorescence guidance with the telomerase-dependent green fluorescent protein (GFP)-containing adenovirus, OBP-401. Viral labelling of the lung tumours with GFP precisely colocalised with tumour RFP expression. Three days after administration of OBP-401, fluorescence-guided surgery (FGS) was performed.ResultsFGS of tumours in the lung was enabled by labelling with a telomerase-dependent adenovirus containing the GFP gene. Tumours in the lung were selectively and brightly labelled. FGS enabled complete lung tumour resection with no residual fluorescent tumour.ConclusionsFGS of tumours in the lung is feasible and more effective than bright-light surgery

Closed-cycle cold helium magic-angle spinning for sensitivity-enhanced multi-dimensional solid-state NMR

AbstractMagic-angle spinning (MAS) NMR is a powerful tool for studying molecular structure and dynamics, but suffers from its low sensitivity. Here, we developed a novel helium-cooling MAS NMR probe system adopting a closed-loop gas recirculation mechanism. In addition to the sensitivity gain due to low temperature, the present system has enabled highly stable MAS (vR=4–12kHz) at cryogenic temperatures (T=35–120K) for over a week without consuming helium at a cost for electricity of 16kW/h. High-resolution 1D and 2D data were recorded for a crystalline tri-peptide sample at T=40K and B0=16.4T, where an order of magnitude of sensitivity gain was demonstrated versus room temperature measurement. The low-cost and long-term stable MAS strongly promotes broader application of the brute-force sensitivity-enhanced multi-dimensional MAS NMR, as well as dynamic nuclear polarization (DNP)-enhanced NMR in a temperature range lower than 100K

Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence.

We have previously developed a genetically-engineered GFP-expressing telomerase-dependent adenovirus, OBP-401, which can selectively illuminate cancer cells. In the present report, we demonstrate that targeting a triple-negative high-invasive human breast cancer, orthotopically-growing in nude mice, with OBP-401 enables curative fluorescence-guided surgery (FGS). OBP-401 enabled complete resection and prevented local recurrence and greatly inhibited lymph-node metastasis due to the ability of the virus to selectively label and subsequently kill cancer cells. In contrast, residual breast cancer cells become more aggressive after bright (white)-light surgery (BLS). OBP-401-based FGS also improved the overall survival compared with conventional BLS. Thus, metastasis from a highly-aggressive triple-negative breast cancer can be prevented by FGS in a clinically-relevant mouse model

The complete mitochondrial genome sequence of the hydrothermal vent galatheid crab Shinkaia crosnieri (Crustacea: Decapoda: Anomura): A novel arrangement and incomplete tRNA suite

<p>Abstract</p> <p>Background</p> <p>Metazoan mitochondrial genomes usually consist of the same 37 genes. Such genes contain useful information for phylogenetic analyses and evolution modelling. Although complete mitochondrial genomes have been determined for over 1,000 animals to date, hydrothermal vent species have, thus far, remained excluded due to the scarcity of collected specimens.</p> <p>Results</p> <p>The mitochondrial genome of the hydrothermal vent galatheid crab <it>Shinkaia crosnieri </it>is 15,182 bp in length, and is composed of 13 protein-coding genes, two ribosomal RNA genes and only 18 transfer RNA genes. The total AT content of the genome, as is typical for decapods, is 72.9%. We identified a non-coding control region of 327 bp according to its location and AT-richness. This is the smallest control region discovered in crustaceans so far. A mechanism of cytoplasmic tRNA import was addressed to compensate for the four missing tRNAs. The <it>S. crosnieri </it>mitogenome exhibits a novel arrangement of mitochondrial genes. We investigated the mitochondrial gene orders and found that at least six rearrangements from the ancestral pancrustacean (crustacean + hexapod) pattern have happened successively. The codon usage, nucleotide composition and bias show no substantial difference with other decapods. Phylogenetic analyses using the concatenated nucleotide and amino acid sequences of the 13 protein-coding genes prove consistent with the previous classification based upon their morphology.</p> <p>Conclusion</p> <p>The present study will supply considerable data of use for both genomic and evolutionary research on hydrothermal vent ecosystems. The mitochondrial genetic characteristics of decapods are sustained in this case of <it>S. crosnieri </it>despite the absence of several tRNAs and a number of dramatic rearrangements. Our results may provide evidence for the immigrating hypothesis about how vent species originate.</p

Improved Resection and Outcome of Colon-Cancer Liver Metastasis with Fluorescence-Guided Surgery Using In Situ GFP Labeling with a Telomerase-Dependent Adenovirus in an Orthotopic Mouse Model.

Fluorescence-guided surgery (FGS) of cancer is an area of intense development. In the present report, we demonstrate that the telomerase-dependent green fluorescent protein (GFP)-containing adenovirus OBP-401 could label colon-cancer liver metastasis in situ in an orthotopic mouse model enabling successful FGS. OBP-401-GFP-labeled liver metastasis resulted in complete resection with FGS, in contrast, conventional bright-light surgery (BLS) did not result in complete resection of the metastasis. OBP-401-FGS reduced the recurrence rate and prolonged over-all survival compared with BLS. In conclusion, adenovirus OBP-401 is a powerful tool to label liver metastasis in situ with GFP which enables its complete resection, not possible with conventional BLS

Development of correlation-based clustering method and its application to software sensing

Abstract The individuality of production devices should be taken into account when soft-sensors are designed for parallelized devices. Since it is expressed as differences of the correlation among measured variables, it is useful to cluster samples on the basis of the correlation among variables for adopting a multi-model approach. In addition, changes in process characteristics can be coped with in the same way. In the present work, a new clustering method, referred to as NC-spectral clustering, is proposed by integrating the nearest correlation (NC) method and spectral clustering. Spectral clustering is a graph partitioning method that can be used for sample classification when an affinity matrix of a weighted graph is given. The NC method can detect samples that are similar to the query from the viewpoint of the correlation without a teacher signal. In the proposed method, the NC method is used for constructing the weighted graph that expresses the correlation-based similarities between samples and the constructed graph is partitioned by using spectral clustering. In addition, a new soft-sensor design method is proposed on the basis of the proposed NCspectral clustering. The usefulness of the proposed methods is demonstrated through a numerical example and a case study of parallelized batch processes. The performance of the proposed correlation-based method is better than that of the conventional distance-based methods