Cancer stem cells induced by chronic stimulation with prostaglandin E2 exhibited constitutively activated PI3K axis

Previously, our group has demonstrated establishment of Cancer Stem Cell (CSC) models from stem cells in the presence of conditioned medium of cancer cell lines. In this study, we tried to identify the factors responsible for the induction of CSCs. Since we found the lipid composition could be traced to arachidonic acid cascade in the CSC model, we assessed prostaglandin E2 (PGE2) as a candidate for the ability to induce CSCs from induced pluripotent stem cells (iPSCs). Mouse iPSCs acquired the characteristics of CSCs in the presence of 10 ng/mL of PGE2 after 4 weeks. Since constitutive Akt activation and pik3cg overexpression were found in the resultant CSCs, of which growth was found independent of PGE2, chronic stimulation of the receptors EP-2/4 by PGE2 was supposed to induce CSCs from iPSCs through epigenetic effect. The bioinformatics analysis of the next generation sequence data of the obtained CSCs proposed not only receptor tyrosine kinase activation by growth factors but also extracellular matrix and focal adhesion enhanced PI3K pathway. Collectively, chronic stimulation of stem cells with PGE2 was implied responsible for cancer initiation enhancing PI3K/Akt axis

Genome Analysis Revives a Forgotten Hybrid Crop Edo-dokoro in the Genus Dioscorea

忘れられた作物「えどどころ」の起原 --ゲノム解析が明らかにする青森県三八上北地域に残る栽培イモの歴史--. 京都大学プレスリリース. 2022-08-10.A rhizomatous Dioscorea crop “Edo-dokoro” was described in old records of Japan, but its botanical identify has not been characterized. We found that Edo-dokoro is still produced by four farmers in Tohoku-machi of Aomori Prefecture, Japan. Rhizomes of Edo-dokoro are a delicacy to the local people and are sold in the markets. Morphological characters of Edo-dokoro suggest its hybrid origin between the two species, D. tokoro and D. tenuipes. Genome analysis revealed that Edo-dokoro is likely originated by hybridization of a male D. tokoro to a female D. tenuipes, followed by a backcross with a male plant of D. tokoro. Edo-dokoro is a typical minor crop possibly maintained for more than 300 years but now almost forgotten from the public. We hypothesize that there are many such uncharacterized genetic heritages passed over generations by small scale farmers that await serious scientific investigation for future use and improvement by using modern genomics information

High-performance pipeline for MutMap and QTL-seq

[Summary] Bulked segregant analysis implemented in MutMap and QTL-seq is a powerful and efficient method to identify loci contributing to important phenotypic traits. However, the previous pipelines were not user-friendly to install and run. Here, we describe new pipelines for MutMap and QTL-seq. These updated pipelines are approximately 5–8 times faster than the previous pipeline, are easier for novice users to use, and can be easily installed through bioconda with all dependencies. [Availability] The new pipelines of MutMap and QTL-seq are written in Python and can be installed via bioconda. The source code and manuals are available online (MutMap: https://github.com/YuSugihara/MutMap, QTL-seq: https://github.com/YuSugihara/QTL-seq)

Bilateral Approach for Thoracoscopic Esophagectomy in a Patient with Esophageal Cancer and Solitary Posterior Thoracic Para-aortic Lymph Node Metastasis

We report a successful dissection of metastatic posterior thoracic para-aortic lymph node (No. 112aoP) via bilateral thoracoscopic surgery. With the anesthetized patient (a 73-year-old Japanese woman) in the prone position, two working ports were inserted for the left-side approach, and artificial pneumothorax was created. Thoracoscopic examination revealed a swollen LN posterior to the descending aorta. Fat and metastatic LNs posterior to the aorta were dissected from the aortic arch level to the diaphragm while preserving intercostal arteries. For the right-side approach, two working ports were inserted and a routine thoracoscopic esophagec-tomy was performed. Gastric conduit reconstruction was achieved laparoscopically. Operation time for the left thoracic procedure: 54 min; estimated blood loss: almost none. No recurrence was detected 24 months post-operatively. There are several surgical options for approaching No. 112aoP, including transhiatal, left thora-cotomy, and thoracoscopy. Although a wide dissection of the posterior thoracic para-aortic area has not been reported, it may be feasible and safe if the artery of Adamkiewicz and intercostal arteries are preserved. A min-imally invasive bilateral thoracoscopic approach for a thoracoscopic esophagectomy is safe and useful for esophageal cancer patients with solitary No. 112aoP metastasis

Supercritical fluid processing of mesoporous crystalline TiO2 thin films for highly efficient dye-sensitized solar cells

In this study, a high light-to-electricity conversion efficiency of 5.14% was achieved by applying a TiO2 thin film with a thickness of 1.87 µm as an electrode material under an AM 1.5 solar light (100 mW cm−2). This high efficiency can be attributed to post-treatment by the supercritical fluid process and the addition of nanoparticles to the thin film. Supercritical fluid treatment is shown to significantly enhance the thermal stability of these thin films. Thus, the high porosity of the treated films was maintained even upon calcination at a high temperature. Additionally, the addition of crystalline light scattering nanoparticles in the thin film not only increases the crystallinity of the thin films but also ensures capture of the incident light and increases the efficiency of light harvesting. The thin film with well-preserved mesopores among the nanoparticles can capture the incident light efficiently and further increase efficiency of light harvesting, which leads to the remarkably high light-to-electricity conversion efficiency

Study protocol of the SACURA trial: a randomized phase III trial of efficacy and safety of UFT as adjuvant chemotherapy for stage II colon cancer

BACKGROUND: Adjuvant chemotherapy for stage III colon cancer is internationally accepted as standard treatment with established efficacy, but the usefulness of adjuvant chemotherapy for stage II colon cancer remains controversial. The major Western guidelines recommend adjuvant chemotherapy for “high-risk stage II” cancer, but this is not clearly defined and the efficacy has not been confirmed. METHODS/DESIGN: SACURA trial is a multicenter randomized phase III study which aims to evaluate the superiority of 1-year adjuvant treatment with UFT to observation without any adjuvant treatment after surgery for stage II colon cancer in a large population, and to identify “high-risk factors of recurrence/death” in stage II colon cancer and predictors of efficacy and adverse events of the chemotherapy. Patients aged between 20 and 80 years with curatively resected stage II colon cancer are randomly assigned to a observation group or UFT adjuvant therapy group (UFT at 500–600 mg/day as tegafur in 2 divided doses after meals for 5 days, followed by 2-day rest. This 1-week treatment cycle is repeated for 1 year). The patients are followed up for 5 years until recurrence or death. Treatment delivery and adverse events are entered into a web-based case report form system every 3 months. The target sample size is 2,000 patients. The primary endpoint is disease-free survival, and the secondary endpoints are overall survival, recurrence-free survival, and incidence and severity of adverse events. In an additional translational study, the mRNA expression of 5-FU-related enzymes, microsatellite instability and chromosomal instability, and histopathological factors including tumor budding are assessed to evaluate correlation with recurrences, survivals and adverse events. DISCUSSION: A total of 2,024 patients were enrolled from October 2006 to July 2010. The results of this study will provide important information that help to improve the therapeutic strategy for stage II colon cancer. TRIAL REGISTRATION: ClinicalTrials.gov NCT00392899

Tumor deposits in colorectal cancer: improving the value of modern staging - a systematic review and meta-analysis

PURPOSE: Colorectal cancer (CRC) treatment is largely determined by tumor stage. Despite improvements made in the treatment of various types of metastatic disease, staging has not been refined. The role of tumor deposits (TD) in staging remains under debate. We have assessed the relation of TD with metastatic pattern, to evaluate whether TD might add significant new information to staging. METHODS: We performed a systematic literature search focused on the role of TD in CRC. Studies with neoadjuvant treated patients were excluded. Data on stage, histological factors and outcome were extracted. Data from four large cohorts were analyzed for the relevance of the presence of TD, lymph node metastases (LNM) and extramural vascular invasion (EMVI) on the pattern of metastases and outcomes. RESULTS: Of the 10,106 included CRC patients 22% presented with TD. TD are invariably associated with poor outcome. The presence of TD was associated with the presence of LNM and EMVI. In a pair wise comparison, the effects of TD were stronger than both LNM and EMVI. In the logistic regression model, TD in combination with LNM is the strongest predictor for liver (odds ratio (OR) 5.5), lung (OR 4.3) and peritoneal metastases (OR 7.0). The presence of EMVI adds information for liver and lung metastases, but not for peritoneal metastases. CONCLUSION: We have shown that TD are not equal to LNM or EMVI, with respect to biology and outcome. We lose valuable prognostic information by allocating TD into nodal category N1c and only considering TD in the absence of LNM. Therefore, we propose that the number of TD should be added to the number of LNM to derive a final N stage

Ablation of the scaffold protein JLP causes reduced fertility in male mice

金沢大学がん研究所がん分子細胞制御The specific and efficient activation of mitogen-activated protein kinase (MAPK) signaling modules is mediated, at least in part, by scaffold proteins. c-Jun NH2-terminal kinase (JNK)-associated leucine zipper protein (JLP) was identified as a scaffold protein for JNK and p38 MAPK signaling modules. JLP is expressed nearly ubiquitously and is involved in intracellular signaling pathways, such as the Gα13 and Cdo-mediated pathway, in vitro. To date, however, JLP expression has not been analyzed in detail, nor are its physiological functions well understood. Here we investigated the expression of JLP in the mouse testis during development. Of the tissues examined, JLP was strongest in the testis, with the most intense staining in the elongated spermatids. Since the anti-JLP antibody used in this study can recognize both JLP and sperm-associated antigen 9 (SPAG9), a splice variant of JLP that has been studied extensively in primates, we also examined its expression in macaque testis samples. Our results indicated that in mouse and primate testis, the isoform expressed at the highest level was JLP, not SPAG9. We also investigated the function of JLP by disrupting the Jlp gene in mice, and found that the male homozygotes were subfertile. Taken together, these observations may suggest that JLP plays an important role in testis during development, especially in the production of functionally normal spermatozoa. © 2008 Springer Science+Business Media B.V

Genome analyses reveal the hybrid origin of the staple crop white Guinea yam (Dioscorea rotundata)

西アフリカの主食作物ギニアヤムの起源を解明 --ギニアヤムはサバンナと熱帯雨林に生育する野生種の雑種起源--. 京都大学プレスリリース. 2020-12-11.White Guinea yam (Dioscorea rotundata) is an important staple tuber crop in West Africa. However, its origin remains unclear. In this study, we resequenced 336 accessions of white Guinea yam and compared them with the sequences of wild Dioscorea species using an improved reference genome sequence of D. rotundata. In contrast to a previous study suggesting that D. rotundata originated from a subgroup of Dioscorea praehensilis, our results suggest a hybrid origin of white Guinea yam from crosses between the wild rainforest species D. praehensilis and the savannah-adapted species Dioscorea abyssinica. We identified a greater genomic contribution from D. abyssinica in the sex chromosome of Guinea yam and extensive introgression around the SWEETIE gene. Our findings point to a complex domestication scenario for Guinea yam and highlight the importance of wild species as gene donors for improving this crop through molecular breeding