CAD1 contributes to osmotic tolerance in Arabidopsis thaliana by suppressing immune responses under osmotic stress.

Acquired osmotolerance induced by initial exposure to mild salt stress is widespread across Arabidopsis thaliana ecotypes, but the mechanism underlying it remains poorly understood. To clarify it, we isolated acquired osmotolerance-deficient 1 (aod1), a mutant highly sensitive to osmotic stress, from ion-beam-irradiated seeds of Zu-0, an ecotype known for its remarkably high osmotolerance. Aod1 showed growth inhibition with spotted necrotic lesions on the rosette leaves under normal growth conditions on soil. However, its tolerance to salt and oxidative stresses was similar to that of the wild type (WT). Genetic and genome sequencing analyses suggested that the gene causing aod1 is identical to CONSTITUTIVELY ACTIVATED CELL DEATH 1 (CAD1). Complementation with the WT CAD1 gene restored the growth and osmotolerance of aod1, indicating that mutated CAD1 is responsible for the observed phenotypes in aod1. Although CAD1 is known to act as a negative regulator of immune response, transcript levels in the WT increased in response to osmotic stress. Aod1 displayed enhanced immune response and cell death under normal growth conditions, whereas the expression profiles of osmotic response genes were comparable to those of the WT. These findings suggest that autoimmunity in aod1 is detrimental to osmotolerance. Overall, our results suggest that CAD1 negatively regulates immune responses under osmotic stress, contributing to osmotolerance in Arabidopsis.

Mutations in nuclear pore complex promote osmotolerance in Arabidopsis by suppressing the nuclear translocation of ACQOS and its osmotically induced immunity.

We have previously reported a wide variation in salt tolerance among Arabidopsis thaliana accessions and identified ACQOS, encoding a nucleotide-binding leucine-rich repeat (NLR) protein, as the causal gene responsible for the disturbance of acquired osmotolerance induced after mild salt stress. ACQOS is conserved among Arabidopsis osmosensitive accessions, including Col-0. In response to osmotic stress, it induces detrimental autoimmunity, resulting in suppression of osmotolerance, but how ACQOS triggers autoimmunity remains unclear. Here, we screened acquired osmotolerance (aot) mutants from EMS-mutagenized Col-0 seeds and isolated the aot19 mutant. In comparison with the wild type (WT), this mutant had acquired osmotolerance and decreased expression levels of pathogenesis-related genes. It had a mutation in a splicing acceptor site in NUCLEOPORIN 85 (NUP85), which encodes a component of the nuclear pore complex. A mutant with a T-DNA insertion in NUP85 acquired osmotolerance similar to aot19. The WT gene complemented the osmotolerant phenotype of aot19. We evaluated the acquired osmotolerance of five nup mutants of outer-ring NUPs and found that nup96, nup107, and aot19/nup85, but not nup43 or nup133, showed acquired osmotolerance. We examined the subcellular localization of the GFP-ACQOS protein and found that its nuclear translocation in response to osmotic stress was suppressed in aot19. We suggest that NUP85 is essential for the nuclear translocation of ACQOS, and the loss-of-function mutation of NUP85 results in acquired osmotolerance by suppressing ACQOS-induced autoimmunity in response to osmotic stress.

[Two Cases of Non-Occlusive Mesenteric Ischemia That Developed after Chemotherapy].

Non-occlusive mesenteric ischemia(NOMI)causes intestinal necrosis due to irreversible ischemia of the intestinal tract despite the absence of organic obstruction in the mesenteric blood vessels. The disease has extremely poor prognosis. We encountered 2 cases of NOMI hypothesized to have developed after chemotherapy; thus, we report these cases considering the available literature. Case 1: A7 9-year-old man. The patient complained of abdominal pain during the first week after introducing docetaxel for local recurrence of prostate cancer. Abdominal computed tomography(CT)revealed mesenteric ischemia and intestinal emphysema. The patient was diagnosed with NOMI, and an emergency operation was performed. Upon laparotomy, the small intestine; ascending, transverse, and descending colon; recto sigmoid; and gall bladder appeared mottled necrotic. As such, all these were excised. He was admitted back to the hospital 3 weeks after surgery due to pneumonia. Case 2: A7 4-year-old man. Combination chemotherapy of docetaxel, cisplatin, and 5-FU was given for oropharyngeal cancer. After 1 week, fever and abdominal pain were noted. Abdominal contrast CT examination was performed, and mesenteric ischemia was confirmed as NOMI. Emergency surgery was performed on the same day. The entire ileum was discolored with mottling, and it was determined to be necrotic. Thus, it was excised. Postoperative course is good, and the patient was followed up after discharge from the hospital. Before NOMI onset in both cases, docetaxel was used to treat myelosuppression. Considering the patient conditions, the association between NOMI onset and docetaxel was suspected. In general, mesenteric ischemia after administration of anticancer drugs is rare, and only a few cases have been reported.

[Radiofrequency Ablation Combined with Hepatectomy for the Treatment of Liver Metastases from Colorectal Cancer].

OBJECTIVE: We evaluated hepatectomy combined with radiofrequency ablation(RFA)in patients with liver metastases from colorectal cancer for which curative resection is difficult. METHODS: This study included 13 patients who underwent hepatectomy combined with RFA for liver metastases from colorectal cancer in or before 2015. RESULTS: In 11 patients who were determined to have achieved a complete curative resection, the 50%survival time was 35.4 months, and the 5-year overall survival (OS)rate was 33%. Recurrence at the RFA site was observed in 4 patients. There were 2 patients with a long-term survival of 5-years or longer. The reasons for concomitant use of RFA include deviation from the Makuuchi criteria in 4 patients, control of disease progression in 3 patients, non-curative surgery in 2 patients, difficulty in performing surgical procedures in 2 patients, and refusal by 1 patient, while the reason was unknown in 1 patient. DISCUSSION: Hepatectomy combined with RFA was selected in patients in whom curative hepatectomy was impossible. Although their 5-year OS rate was lower than that of patients who undergo hepatectomy alone, local control was relatively favorable. CONCLUSION: These results suggest that hepatectomy combined with RFA for liver metastases from colorectal cancer might be effective in selected cases.

[Two case reports with hepatic metastases of colorectal cancer treated with radiofrequency ablation, raising the possibility of local control in the liver].

Only hepatic metastasectomy has been shown to have a therapeutic effect for hepatic metastases of colorectal cancer if the primary tumor can be removed radically according to the 2014 guidelines of the Japanese Society for Cancer of the Colon and Rectum. However, only a few patients with hepatic metastases are candidates for metastasectomy due to tumor factors other than the hepatic metastases. Furthermore, hepatic metastasectomy is frequently judged to be impossible in older patients due to underlying diseases and surgical tolerability. In such cases, therefore, treatment is often difficult. Herein, we report 2 patients with hepatic metastases of colorectal cancer treated with radiofrequency ablation, raising the possibility of local control in the liver.

Biomarker Discovery of Pancreatic and Gastrointestinal Cancer by 2DICAL: 2-Dimensional Image-Converted Analysis of Liquid Chromatography and Mass Spectrometry.

Biomarkers tested by blood sample are of great use to clinicians as they provide useful information to aid an early and accurate diagnosis. Comprehensive "omics" studies are expected to facilitate the identification of such new biomarkers, and much research is being performed in this area. Our proteomics analysis system of 2-dimensional image-converted analysis of liquid chromatography and mass spectrometry (2DICAL) has successfully identified several new blood biomarkers from the clinical blood samples of pancreatic and colorectal cancer patients.

Plasma biomarker discovery and validation for colorectal cancer by quantitative shotgun mass spectrometry and protein microarray.

The development of a new plasma biomarker for early detection would be necessary to improve the overall outcome of colorectal cancer. Here we report the identification and validation of the ninth component of complement (C9) as a novel plasma biomarker for colorectal cancer by cutting-edge proteomic technologies. Plasma proteins were enzymatically digested into a large array of peptides, and the relative quantity of a total of 94,803 peptide peaks was compared between 31 colorectal cancer patients and 59 age/sex-matched healthy controls using 2D image-converted analysis of liquid chromatography and mass spectrometry. The selected biomarker candidates were validated in 345 subjects (115 colorectal cancer patients and 230 age/sex-matched healthy controls) using high-density reverse-phase protein microarrays. Plasma levels of Apo AI and C9 in colorectal cancer patients significantly differed from healthy controls with P values of 7.94×10(-4) and 1.43×10(-12) (Student's t-test), respectively. In particular, C9 was elevated in patients with colorectal cancer, including those with stage-I and -II diseases (P=3.01×10(-3) and P=1.13×10(-5) , respectively). Although the significance of the present study must be validated in an independent clinical study, the increment of plasma C9 may be applicable to the early detection of colorectal cancer.

[More than 20 years of long-term survival case of intraabdominal GIST by combined therapies with frequent surgeries].

A jejunum partial resection was performed on a 49-year-old female for jejunum leiomyosarcoma of 7 cm in 1990. She was resected four times for recurrent tumors from 1993 to 2004. We started an internal use of imatinib in 2003, because we could get a diagnosis of GIST. After the surgery of 2004, she stopped taking the internal use of imatinib, but an intraabdominal recurrence occurred in 2006 and she restarted taking the internal use of imatinib.