Local relapse of nasopharyngeal cancer and Voxel-based analysis of FMISO uptake using PET with semiconductor detectors

Background: Hypoxic cancer cells are thought to be radioresistant and could impact local recurrence after radiotherapy (RT). One of the major hypoxic imaging modalities is [18F]fluoromisonidazole positron emission tomography (FMISO-PET). High FMISO uptake before RT could indicate radioresistant sites and might be associated with future local recurrence. The predictive value of FMISO-PET for intra-tumoral recurrence regions was evaluated using high-resolution semiconductor detectors in patients with nasopharyngeal carcinoma after intensity-modulated radiotherapy (IMRT). Methods: Nine patients with local recurrence and 12 patients without local recurrence for more than 3 years were included in this study. These patients received homogeneous and standard doses of radiation to the primary tumor irrespective of FMISO uptake. The FMISO-PET image before RT was examined via a voxel-based analysis, which focused on the relationship between the degree of FMISO uptake and recurrence region. Results: In the pretreatment FMISO-PET images, the tumor-to-muscle ratio (TMR) of FMISO in the voxels of the tumor recurrence region was significantly higher than that of the non-recurrence region (p < 0.0001). In the recurrent patient group, a TMR value of 1.37 (95% CI: 1.36-1.39) corresponded to a recurrence rate of 30%, the odds ratio was 5.18 (4.87-5.51), and the area under the curve (AUC) of the receiver operating characteristic curve was 0.613. In all 21 patients, a TMR value of 2.42 (2.36-2.49) corresponded to an estimated recurrence rate of 30%, and the AUC was only 0.591. Conclusions: The uptake of FMISO in the recurrent region was significantly higher than that in the non-recurrent region. However, the predictive value of FMISO-PET before IMRT is not sufficient for up-front dose escalation for the intra-tumoral high-uptake region of FMISO. Because of the higher mean TMR of the recurrence region, a new hypoxic imaging method is needed to improve the sensitivity and specificity for hypoxia

High-throughput, quantitative analyses of genetic interactions in E. coli.

Large-scale genetic interaction studies provide the basis for defining gene function and pathway architecture. Recent advances in the ability to generate double mutants en masse in Saccharomyces cerevisiae have dramatically accelerated the acquisition of genetic interaction information and the biological inferences that follow. Here we describe a method based on F factor-driven conjugation, which allows for high-throughput generation of double mutants in Escherichia coli. This method, termed genetic interaction analysis technology for E. coli (GIANT-coli), permits us to systematically generate and array double-mutant cells on solid media in high-density arrays. We show that colony size provides a robust and quantitative output of cellular fitness and that GIANT-coli can recapitulate known synthetic interactions and identify previously unidentified negative (synthetic sickness or lethality) and positive (suppressive or epistatic) relationships. Finally, we describe a complementary strategy for genome-wide suppressor-mutant identification. Together, these methods permit rapid, large-scale genetic interaction studies in E. coli

[18F]fluoromisonidazole and a New PET System With Semiconductor Detectors and a Depth of Interaction System for Intensity Modulated Radiation Therapy for Nasopharyngeal Cancer

Purpose: The impact of a new type of positron emission tomography with semiconductor detectors (New PET) on an 18F-fluoromisonidazole (FMISO)-guided intensity-modulated radiation therapy (IMRT) plan was investigated by comparing the plan with the use of a state-of-the-art PET/computed tomography system (PET/CT) in nasopharyngeal cancer (NPC) patients. Methods and Materials: Twenty-four patients with non-NPC malignant tumors (control group) and 16 patients with NPC were subjected to FMISO-PET. The threshold of the tumor-to-muscle (T/M) ratio in each PET scan was calculated. The hypoxic volume within the gross tumor volume was determined using each PET ([NewPET]GTVh and [PET/CT]GTVh, respectively). Dose-escalation IMRT plans prescribing 84Gy to each GTVh were carried out. Results: The threshold of the T/M ratio was calculated to be 1.35 for New PET and 1.23 for PET/CT. The mean volume of [NewPET]GTVh was significantly smaller than that of [PET/CT]GTVh (1.5±1.6cc vs. 4.7±4.6cc, respectively, P =0.0020). The dose-escalation IMRT plans using New PET were superior in dose distribution to those using PET/CT. Dose escalation was possible in all 10 New PET-guided plans but not in one PET/CT-guided plan, because the threshold dose to the brainstem was exceeded. Conclusion: New PET was suggested to be useful for accurate dose escalation in FMISO-guided IMRT for patients with NPC

Genome-scale identification and characterization of moonlighting proteins

Moonlighting proteins perform two or more cellular functions, which are selected based on various contexts including the cell type they are expressed, their oligomerization status, and the binding of different ligands at different sites. To understand overall landscape of their functional diversity, it is important to establish methods that can identify moonlighting proteins in a systematic fashion. Here, we have developed a computational framework to find moonlighting proteins on a genome scale and identified multiple proteomic characteristics of these proteins

Colony-live --a high-throughput method for measuring microbial colony growth kinetics-- reveals diverse growth effects of gene knockouts in Escherichia coli

Precise quantitative growth measurements and detection of small growth changes in high-throughput manner is essential for fundamental studies of bacterial cell. However, an inherent tradeoff for measurement quality in high-throughput methods sacrifices some measurement quality. A key challenge has been how to enhance measurement quality without sacrificing throughput

Automated amplification-free digital RNA detection platform for rapid and sensitive SARS-CoV-2 diagnosis

新型コロナウイルスの超高感度・全自動迅速検出装置の開発 --汎用的な感染症診断装置としての社会実装に期待--. 京都大学プレスリリース. 2022-05-27.In the ongoing COVID-19 pandemic, rapid and sensitive diagnosis of viral infection is a critical deterrent to the spread of SARS-CoV-2. To this end, we developed an automated amplification-free digital RNA detection platform using CRISPR-Cas13a and microchamber device (opn-SATORI), which automatically completes a detection process from sample mixing to RNA quantification in clinical specimens within ~9 min. Using the optimal Cas13a enzyme and magnetic beads technology, opn-SATORI detected SARS-CoV-2 genomic RNA with a LoD of < 6.5 aM (3.9 copies μL⁻¹), comparable to RT-qPCR. Additionally, opn-SATORI discriminated between SARS-CoV-2 variants of concern, including alpha, delta, and omicron, with 98% accuracy. Thus, opn-SATORI can serve as a rapid and convenient diagnostic platform for identifying several types of viral infections

iML1515, a knowledgebase that computes Escherichia coli traits

<p>(A) Discovery and (B) Validation. The bars represent the number of samples with ER positive and negative in the five intrinsic subtypes, based on the patients’ clinical information. The top row is based on the original subtype labels obtained with the PAM50 list and a single classifier (PAM). Middle and bottom rows are based on the labels obtained by Ensemble Learning using the PAM50 and CM1 lists, respectively.</p