Fusobacterium nucleatum confers chemoresistance by modulating autophagy in oesophageal squamous cell carcinoma

Background Fusobacterium nucleatum (F. nucleatum) is a gut microbe implicated in gastrointestinal tumorigenesis. Predicting the chemotherapeutic response is critical to developing personalised therapeutic strategies for oesophageal cancer patients. The present study investigated the relationship between F. nucleatum and chemotherapeutic resistance in oesophageal squamous cell carcinoma (ESCC).Methods We examined the relationship between F. nucleatum and chemotherapy response in 120 ESCC resected specimens and 30 pre-treatment biopsy specimens. In vitro studies using ESCC cell lines and co-culture assays further uncovered the mechanism underlying chemotherapeutic resistance.Results ESCC patients with F. nucleatum infection displayed lesser chemotherapeutic response. The infiltration and subsistence of F. nucleatum in the ESCC cells were observed by transmission electron microscopy and laser scanning confocal microscopy. We also observed that F. nucleatum modulates the endogenous LC3 and ATG7 expression, as well as autophagosome formation to induce chemoresistance against 5-FU, CDDP, and Docetaxel. ATG7 knockdown resulted in reversal of F. nucleatum-induced chemoresistance. In addition, immunohistochemical studies confirmed the correlation between F. nucleatum infection and ATG7 expression in 284 ESCC specimens.Conclusions F. nucleatum confers chemoresistance to ESCC cells by modulating autophagy. These findings suggest that targeting F. nucleatum, during chemotherapy, could result in variable therapeutic outcomes for ESCC patients.Subject terms: Tumour biomarkers, Oesophageal cancer     

Phlebosclerotic colitis that was difficult to distinguish from collagenous colitis

Phlebosclerotic colitis is a rare and recently known disease entity and its etiology is still to be elucidated. Some phlebosclerotic colitis cases are difficult to distinguish from collagenous colitis because of the similarity of pathological findings. In all Japanese case reports of phlebosclerotic colitis in which an association with the use of Chinese herbal medicine is suspected, sansisi (gardenia fruit) was included, suggesting pathogenesis of this disease. We report a case of phlebosclerotic colitis that wasdifficult to be distinguished from collagenous colitis, and an association with the use of Chinese herbal medicine was suspected as the cause of the disease.     

Dysembryoplastic neuroepithelial tumor in the insular cortex. Three dimensional magnetoencephalographic localization of epileptic discharges

Abstract

A case of dysembryoplastic neuroepithelial tumor in the left insular cortex manifesting with intractable seizures is presented. The multichannel magnetoencephalography (MEG) localized equivalent current dipoles of epileptic discharges at the cerebral cortex adjacent to the tumor. The total removal of the tumor resulted in complete disappearance of seizures. This case demonstrated that multichannel MEG was useful in the three-dimensional localization of irritative zone in the concealed cortices such as inside the sylvian fissure. [Neural Res 1998; 20: 433–438]     

Heparin-induced thrombocytopenia with multiple organized thrombi accompanied by unusual cholesterin deposition: Autopsy case after long-term follow up

Heparin-induced thrombocytopenia (HIT) is characterized by a reduction in the platelet count and systemic thromboembolism during heparin therapy. Herein is reported a case of HIT with characteristic thrombus formation. A 68-year-old man who had been treated for hypertension for 27 years suffered a brain infarction and was treated with heparin. After this treatment, other new infarctions occurred in multiple organs. Because serum antibodies against heparin/PF4 complex were detected, he was diagnosed as having HIT, and warfarin and argatroban were administered instead of heparin. He died, however, 119 days after the first onset. At autopsy infarction due to organized thrombi with cholesterin deposition in multiple organs were found, similar to usual atherosclerotic emboli, but different to them with regard to clinical course and distribution of thrombi. This case in which organization and frequent cholesterin deposition were found in thromboembolized lesions of multiple organs after relatively long-term follow up, is unusual. The findings suggest that HIT accompanied by marked hypercholesterolemia of long duration contributes to a characteristic form of thromboembolism that needs careful management.     

Recurrence of hepatocellular carcinoma 102 months after successful eradication and removal of membranous obstruction of the inferior vena cava

We report a 54-year-old Japanese woman who developed liver tumors 102 months after hepatic resection for hepatocellular carcinoma (HCC) and percutaneous transluminal angioplasty (PTA) for membranous obstruction of the inferior vena cava (MOVC), which is one form of Budd-Chiari syndrome. In the present admission workup showed no evidence of co-infection with hepatitis B and C viruses. Dynamic computed tomography (CT) and magnetic resonance imaging showed an enhanced lesion, 1.5cm in diameter, in segment 3 of the liver, and no obstruction of the inferior vena cava after PTA. CT during both arterial portography and hepatic arteriography revealed another lesion, showing different hemodynamics, in segment 2. The patient therefore underwent hepatic resection, and the tumors were diagnosed histologically as HCC. The two tumors differed in their morphological features, one containing abundant fibrous stroma, whereas the other did not. The nontumorous liver tissue showed central zonal fibrosis, i.e., reversed lobulation, and partial expansion of nodule-like formations, indicating lack of progression since the situation seen at the initial hepatectomy. The presence of nontumorous liver tissue showing the above features suggests that, even after successful treatment for relief of congestion, patients who have had MOVC should be followed closely for as long as possible because of the risk of HCC recurrence. This is the first reported case of HCC recurrence after successful treatment of MOVC.     

Comparison of the clinical courses of the opticospinal and conventional forms of multiple sclerosis in Japan

We evaluated the clinical courses of 216 patients with multiple sclerosis (MS) diagnosed according to the recommended diagnostic criteria of McDonald et al (10). Sixty-five patients clinically displaying selective involvement of the optic nerves and spinal cord were classified as opticospinal MS (OS-MS), while the other 151 showing disseminated involvement of the central nervous system were classified as conventional MS (C-MS). The disease duration did not differ significantly between the two subtypes (11.2 years vs. 11.5 years). In addition to a higher age of onset, female preponderance and higher Kurtzke's expanded disability status scale (EDSS) scores, the OS-MS patients showed a markedly lower frequency of secondary progressive MS than the C-MS patients (4.6% vs. 29.1%, p=0.0001). The EDSS scores of the C-MS patients were significantly correlated with the disease duration, while those of the OS-MS patients were not. Among the C-MS patients, the frequency of secondary progressive MS was significantly more common in patients with a disease duration of more than 10 years than in those with a shorter duration. These results suggest that the irreversible disability in OS-MS is determined by relapses, rather than by chronic progression, whereas C-MS has a similar clinical course to MS in Westerners.     

Cholesterol crystal embolization (CCE) after cardiac catheterization: a case report and a review of 36 cases in the Japanese literature

Cholesterol crystal embolization (CCE) is a complication of atherosclerosis. A 67-year-old Japanese man underwent coronary artery bypass grafting. After the surgery, he underwent coronary angiography via the right femoral artery. Twelve days later, he suddenly developed acalculous cholecystitis and was treated with antibiotics. Gradual deterioration in renal function, purplish discoloration of the distal portion of his toes, and eosinophilia were noted. We performed a skin biopsy and made a diagnosis of CCE. Cilostazol and intravenous heparin improved the symptoms and decreased the creatinine level. We retrospectively studied the clinical features of 36 cases registered with a diagnosis of CCE in the Japanese literature.