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The potential diagnostic significance of crypt differentiation in gastric dysplasia

This study investigated the relationship between the differentiation of tumour cells into crypts, which is determined by cell differentiation into Paneth and neuroendocrine cells, and tumour infiltration in gastric dysplasia. The lesions were endoscopically biopsied low-grade dysplasia (LGD), endoscopically resected high-grade dysplasia (HGD) or cancer with submucosal invasion. LGD (n = 32) displayed crypt differentiation across the entire width of the tumour in all cases. Crypt differentiation was identified as a characteristic of tumours with low biological malignancy. HGD (n = 40) included tumours with a mixture of areas with and without crypt differentiation (n = 25) and tumours with crypt differentiation throughout the entire width (n = 15). Of the cancers with submucosal invasion (n = 30), the morphological progression of the HGD area with crypt differentiation, the HGD area without crypt differentiation and invasive cancer without crypt differentiation was confirmed for 23 samples. In two lesions, invasive cancer without crypt differentiation developed from HGD without crypt differentiation throughout the tumour width. In five samples, well-differentiated tubular adenocarcinoma with crypt differentiation developed from HGD with crypt differentiation and invaded with lamina propria-like stroma. Loss of crypt differentiation could be an objective indicator of infiltration in the progression of HGD to invasive cancer. The invasive potential of dysplasia depends upon the presence or absence of crypt differentiation.

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Hokuriku-plus familial hypercholesterolaemia registry study: rationale and study design

IntroductionFamilial hypercholesterolaemia (FH) is an autosomal-dominant inherited genetic disease. It carries an extremely high cardiovascular risk associated with significantly elevated low-density lipoprotein (LDL) cholesterol. The diagnostic rate of this disease in some European nations is quite high, due to the presence of multiple prospective registries. On the other hand, few data—and in particular multicentre data—exist regarding this issue among Japanese subjects. Therefore, this study intends to assemble a multicentre registry that aims to comprehensively assess cardiovascular risk among Japanese FH patients while taking into account their genetic backgrounds.Methods and analysisThe Hokuriku-plus FH registry is a prospective, observational, multicentre cohort study, enrolling consecutive FH patients who fulfil the clinical criteria of FH in Japan from 37 participating hospitals mostly in Hokuriku region of Japan from April 2020 to March 2024. A total of 1000 patients will be enrolled into the study, and we plan to follow-up participants over 5 years. We will collect clinical parameters, including lipids, physical findings, genetic backgrounds and clinical events covering atherosclerotic and other important events, such as malignancies. The primary endpoint of this study is new atherosclerotic cardiovascular disease (ASCVD) events. The secondary endpoints are as follows: LDL cholesterol, secondary ASCVD events and the occurrence of other diseases including hypertension, diabetes and malignancies.Ethics and disseminationThis study is being conducted in compliance with the Declaration of Helsinki, the Ethical Guidelines for Medical and Health Research Involving Human Subjects, and all other applicable laws and guidelines in Japan. This study protocol has been approved by the Institutional Review Board at Kanazawa University. We will disseminate the final results at international conferences and in a peer-reviewed journal.Trial registration numberUMIN000038210.

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Resection of distal gastric tube cancer with sentinel node biopsy: a case report and review of the literature.

BackgroundThe frequency of gastric tube cancershas increased with advances in surgical techniques and improvement of survival rates in patients with esophageal cancer. However, a standard surgical treatment has not yet been established. Total resection of the gastric tube with lymphadenectomy has been considered a radical treatment, while repeat surgery with both laparotomy and thoracotomy has been associated with severe complications, including anastomotic leakage, recurrent nerve paralysis, bronchotracheal injury, and damage to other organs.Case presentationWe present a successful case of a gastric tube cancer that was treated with surgical resection in combination with sentinel node biopsy. The tumor was diagnosed as a type 0-IIc lesion with ulceration, and was located proximal to the pyloric ring. Endoscopic submucosal dissection was not indicated because the primary lesion was submucosally invasive, and undifferentiated. By the dye-guided method, sentinel nodes were detected along the right gastroepiploic artery and vein. Intraoperative pathological examination revealed no metastasis of the sentinel nodes. Resection of the distal gastric tube was safely performed with a Roux-en-Y reconstruction, preserving the right gastroepiploic artery and vein and the perfusion of the proximal gastric tube.ConclusionWe suggest distal resection of the gastric tube with sentinel node biopsy as a novel surgical method for a cT1N0 gastric tube cancer located in the abdomen.

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Expression and characterization of styrene monooxygenases of Rhodococcus sp. ST-5 and ST-10 for synthesizing enantiopure (S)-epoxides

Styrene monooxygenase (StyA, SMOA)- and flavin oxidoreductase (StyB, SMOB)-coding genes of styrene-assimilating bacteria Rhodococcus sp. ST-5 and ST-10 were successfully expressed in Escherichia coli. Determined amino acid sequences of StyAs and StyBs of ST-5 and ST-10 showed more similarity with those of Pseudomonas than with self-sufficient styrene monooxygenase (StyA2B) of Rhodococcus. Recombinant enzymes were purified from E. coli cells as functional proteins, and their properties were characterized in detail. StyBs (flavin oxidoreductase) of strains ST-5 and ST-10 have similar enzymatic properties to those of Pseudomonas, but StyB of strain ST-10 exhibited higher temperature stability than that of strain ST-5. StyAs of strains ST-5 and ST-10 catalyzed the epoxidation of vinyl side-chain of styrene and its derivatives and produced (S)-epoxides from styrene derivatives and showed high stereoselectivity. Both StyAs showed higher specific activity on halogenated styrene derivatives than on styrene itself. Additionally, the enzymes could catalyze the epoxidation of short-chain 1-alkenes to the corresponding (S)-epoxides. Aromatic compounds including styrene, 3-chlorostyrene, styrene oxide, and benzene exhibited marked inhibition of SMO reaction, although linear 1-alkene showed no inhibition of SMO activity at any concentration.

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Caffeine-potentiated chemotherapy for clear cell sarcoma: a report of five cases

Clear cell sarcoma is a rare malignant tumor of soft tissue which is most commonly encountered in the extremities, especially in the foot and ankle. This tumor is slow-growing and looks like a benign tumor; it is therefore often treated inadequately and its high rate of recurrence and metastases results in a poor prognosis. Caffeine has been used as a chemotherapy potentiator that inhibits DNA damage repair and enhances the cytocidal effects of anti-cancer drugs. This study reports the effect of caffeine-potentiated chemotherapy for clear cell sarcoma in five patients. Caffeine-potentiated chemotherapy was administered to five patients with clear cell sarcoma. Three to five courses of intra-arterial chemotherapy using cisplatin, doxorubicin and caffeine were administered preoperatively, at 3-week intervals. Conservatively, wide margin surgery was performed following the preoperative chemotherapy. Intravenous cisplatin and doxorubicin with caffeine were administered three to six times to the patients who responded to the preoperative chemotherapy. This study evaluated the response to chemotherapy, recurrence, metastasis and the overall prognosis in these five patients. Four of the eligible patients responded to preoperative chemotherapy. Local recurrence occurred in only one of the five patients. Distant metastasis newly developed in one patient. All five patients survive. Caffeine-potentiated chemotherapy can be effective treatment for clear cell sarcoma not only as initial therapy, but also as salvage therapy.

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Open Access