ダイドウミャク サシュキカンシ ニ シンジュン シタ コウド シンコウ キョウブ ショクドウガン ニ タイシ weekly DOC＋ low-dose FP リョウホウ ガ ソウコウシ コンチ セツジョ シエタ イチレイ

A ７０s woman was pointed out lower thoracic advanced esophageal squamous cell carcinoma with a chief complaint of dysphagia by upper gastrointestinal endoscopy. Computed tomography （CT）revealed that original tumor invaded to aorta and left main bronchus. Weekly docetaxel plus low-dose ５-FU and cisplatin therapy decreased the tumor. The invasion to aorta and left main bronchus was disappeared. She underwent curative esophagectomy. Main tumor had wide adherence to left main bronchus and aorta but was able to be resected. She underwent subtotal esophagectomy and gastric tube reconstruction by retrosternal route. Pathological diagnosis revealed carcinoma invaded from submucosa to adventitia and deep margin was negative（pT３）. Advanced esophageal carcinoma with invasion to aorta and main bronchus is commonly treated by definitive chemoradiotherapy and hardly undergo curative resection. This case underwent curative resection after only chemotherapy. This case suggests excellent anticancer effect of the triple drug therapy

キュウシン コウヒショウ オ ケイキ ニ シンダンサレ フククウキョウカ ニ セツジョ サレタ ソウキ チョクチョウガン ノ 1レイ

An 82-year-old man had systemic rash and itching. He was treated with antihistamines and steroids, but did not improve. We continued treatment at our hospital, but there was no improvement.The deck-chair sign was observed during treatment, and we diagnosed papuloerythroderma. We considered the possibility of merged malignant tumors and carried out a detailed examination.The final diagnosis was clinical stage I rectal cancer. The patient underwent laparoscopic low anterior resection. The refractory systemic rash completely improved by the 23th postoperative day. At present, the rectal cancer has not relapsed for 4 years after the operation

The effects of the herbal medicine Daikenchuto (TJ-100) after esophageal cancer resection, open-label, randomized controlled trial

Background Daikenchuto (TJ-100), a traditional Japanese herbal medicine, is widely used in Japan. Its effects on gastrointestinal motility and microcirculation and its anti-inflammatory effect are known. The purpose of this prospective randomized controlled trial was to investigate the effect of TJ-100 after esophagectomy in esophageal cancer patients. Methods Forty patients for whom subtotal esophageal resection for esophageal cancer was planned at our institute from March 2011 to August 2013 were enrolled and divided into two groups at the point of determination of the operation schedule after informed consent was obtained: a TJ-100 (15 g/day)-treated group (n = 20) and a control group (n = 20). The primary efficacy end-points were maintenance of the nutrition condition and the recovery of gastrointestinal function. The secondary efficacy end-points were the serum C-reactive protein (CRP) level and adrenomedullin level during the postoperative course, the incidence of postoperative complications, and the length of hospital stay after surgery. Results We examined 39 patients because one patient in the TJ-100 group was judged as having unresectable cancer after surgery. The mean age of the TJ-100 group patients was significantly older than that of the control group patients.The rate of body weight decrease at postoperative day 21 was significantly suppressed in the TJ-100 group (3.6% vs. the control group: 7.0%, p = 0.014), but the serum albumin level was not significantly different between the groups. The recovery of gastrointestinal function regarding flatus, defecation, and oral intake showed no significant between-group differences, but postoperative bowel symptoms tended to be rare in the TJ-100 group. There was no significant between-group difference in the length of hospital stay after surgery. The serum CRP level at postoperative day 3 was 4.9 mg/dl in the TJ-100 group and 6.9 mg/dl in the control group, showing a tendency of a suppressed serum CRP level in the TJ-100 group (p = 0.126). The rate of increase in adrenomedullin tended to be high postoperatively, but there was no significant difference between the two groups. Conclusions TJ-100 treatment after esophageal cancer resection has the effects of prompting the recovery of gastrointestinal motility and minimizing body weight loss, and it might suppress the excess inflammatory reaction related to surgery

Comprehensive study of liposome-assisted synthesis of membrane proteins using a reconstituted cell-free translation system

Membrane proteins play pivotal roles in cellular processes and are key targets for drug discovery. However, the reliable synthesis and folding of membrane proteins are significant problems that need to be addressed owing to their extremely high hydrophobic properties, which promote irreversible aggregation in hydrophilic conditions. Previous reports have suggested that protein aggregation could be prevented by including exogenous liposomes in cell-free translation processes. Systematic studies that identify which membrane proteins can be rescued from irreversible aggregation during translation by liposomes would be valuable in terms of understanding the effects of liposomes and developing applications for membrane protein engineering in the context of pharmaceutical science and nanodevice development. Therefore, we performed a comprehensive study to evaluate the effects of liposomes on 85 aggregation-prone membrane proteins from Escherichia coli by using a reconstituted, chemically defined cell-free translation system. Statistical analyses revealed that the presence of liposomes increased the solubility of >90% of the studied membrane proteins, and ultimately improved the yields of the synthesized proteins. Bioinformatics analyses revealed significant correlations between the liposome effect and the physicochemical properties of the membrane proteins

CD153/CD30 signaling promotes age-dependent tertiary lymphoid tissue expansion and kidney injury

高齢者腎臓病を悪化させる原因細胞・分子の同定に成功. 京都大学プレスリリース. 2021-11-30.A new drug target for kidney disease. 京都大学プレスリリース. 2021-11-30.Tertiary lymphoid tissues (TLTs) facilitate local T- and B-cell interactions in chronically inflamed organs. However, the cells and molecular pathways that govern TLT formation are poorly defined. Here we identify TNF superfamily CD153-CD30 signaling between two unique age-dependent lymphocyte subpopulations, CD153⁺PD-1⁺CD4⁺ senescence-associated T (SAT) cells and CD30+T-bet+ age-associated B cells (ABCs), as a driver for TLT expansion. SAT cells, which produced ABC-inducing factors IL21 and IFNγ, and ABCs progressively accumulated within TLTs in aged kidneys after injury. Notably, in kidney injury models, CD153 or CD30 deficiency impaired functional SAT cell induction, which resulted in reduced ABC numbers and attenuated TLT formation with improved inflammation, fibrosis and renal function. Attenuated TLT formation after transplantation of CD153-deficient bone marrow further supported the importance of CD153 in immune cells. Clonal analysis revealed that SAT cells and ABCs in the kidneys arose from both local differentiation and recruitment from the spleen. In the synovium of aged rheumatoid arthritis patients, T peripheral helper/T follicular helper cells and ABCs also expressed CD153 and CD30, respectively. Together, our data reveal a previously unappreciated function of CD153-CD30 signaling in TLT formation and propose targeting CD153-CD30 signaling pathway as a therapeutic target for slowing kidney disease progression

Glutamine protects small intestinal mucosa

Supportive therapy during chemotherapy has become essential, but effective preventive therapies to gastrointestinal mucosal injury are few. We investigated the efficacy of glutamine in rat anticancer drug-induced enteritis model. In this study, we used twenty male SD rats. They were divided into control, 5-fluorouracil (5-FU) (orally administered at 20mg/kg day), 5-FU+glutamine (1000 mg/kg/day) and 5-FU+glutamine+fiber and oligosaccharide (GFO[○R]) (1000 mg/kg/day) groups. All groups were sacrificed on day 6 and upper jejunums were excised. The jejunal villous height was measured in specimens. IgA level in jejunal washing solution, and serum diamine oxidase activity were also measured. The jejunal villous height was recognized as shorter in the specimen from 5-FU treated rats compared with 5-FU+glutamine treated rats (p<0.001). Serum diamine oxidase activity in 5-FU+glutamine group were significantly superior to that in 5-FU group (p=0.028). IgA level in jejunal washing solution tended to be higher in 5-FU+glutamine group than that in 5-FU group (p=0.076). On the other hand, serum diamine oxidase activity and IgA level in jejunal washing solution showed no significant difference between 5-FU+GFO and 5-FU treatment group. Our results suggest that glutamine showed protective effects on mucosal injury of small intestine in rat anticancer drug-induced enteritis model

Dramatic Transcriptional Changes in an Intracellular Parasite Enable Host Switching between Plant and Insect

Phytoplasmas are bacterial plant pathogens that have devastating effects on the yields of crops and plants worldwide. They are intracellular parasites of both plants and insects, and are spread among plants by insects. How phytoplasmas can adapt to two diverse environments is of considerable interest; however, the mechanisms enabling the “host switching” between plant and insect hosts are poorly understood. Here, we report that phytoplasmas dramatically alter their gene expression in response to “host switching” between plant and insect. We performed a detailed characterization of the dramatic change that occurs in the gene expression profile of Candidatus Phytoplasma asteris OY-M strain (approximately 33% of the genes change) upon host switching between plant and insect. The phytoplasma may use transporters, secreted proteins, and metabolic enzymes in a host-specific manner. As phytoplasmas reside within the host cell, the proteins secreted from phytoplasmas are thought to play crucial roles in the interplay between phytoplasmas and host cells. Our microarray analysis revealed that the expression of the gene encoding the secreted protein PAM486 was highly upregulated in the plant host, which is also observed by immunohistochemical analysis, suggesting that this protein functions mainly when the phytoplasma grows in the plant host. Additionally, phytoplasma growth in planta was partially suppressed by an inhibitor of the MscL osmotic channel that is highly expressed in the plant host, suggesting that the osmotic channel might play an important role in survival in the plant host. These results also suggest that the elucidation of “host switching” mechanism may contribute to the development of novel pest controls