ASO Visual Abstract: Influence of Damaged Stomach on Anastomotic Leakage After Cervical Esophagogastrostomy for Patients with Esophageal Cancer

Annals of Surgical Oncology -     

Longitudinal assessment of anti-Müllerian hormone after cesarean section and influence of bilateral salpingectomy on ovarian reserve

ObjectiveThis study aimed to compare longitudinal changes in ovarian reserve markers after cesarean section (CS) with and without bilateral salpingectomy (BS).Study designWe prospectively enrolled women >35 weeks’ gestation scheduled for CS alone or CS + BS and obtained blood samples for anti-Müllerian hormone prior to surgery and at 3 and 6 months after surgery. At the 3-month visit, we similarly performed transvaginal ultrasound for antral follicle count.ResultsWe enrolled 50 women; 30 underwent CS only and 20 underwent CS + BS. Although anti-Müllerian hormone level increased over 6 months of follow-up in both groups, no clinically important differences in the geometric mean (interquartile range) (ng/mL) were observed at any timepoint (baseline [0.69 {0.36?1.21} {CS only} vs 0.49 {0.32?2.10} {CS + BS}, p = 0.64]; 3 months [1.35 {0.58?3.13} vs 1.45 {1.04?2.25}, p = 0.79]; and 6 months [1.74 {0.93?4.45} vs 2.60 {1.41?5.10}, p =0.27]). Similarly, we detected no difference in antral follicle count.ConclusionBS at the time of CS does not have a negative impact on ovarian reserve 6 months after surgery.ImplicationWhile our results provide reassuring data that bilateral salpingectomy for permanent contraception at the time of cesarean section does not impact ovarian reserve, longer adequately powered studies are needed.     

Vaccination with chimeric protein induces protection in murine model against ascariasis

An estimated 400 million people are infected by parasites of the genus Ascaris and the existing control measures are inefficient. Vaccine development using B cell antigens is a promising strategy for increased protection against this parasite. The present study aimed at developing a chimeric protein capable of conferring protection against infection by Ascaris sp. For this purpose, we performed B-cell epitope predictions on previously described vaccine candidate proteins from Ascaris suum and the corresponding peptides were used to construct a chimeric protein. Female BALB / c mice were immunized subcutaneously in three doses at 10 day intervals with a vaccine formulation comprised of the chimeric protein together with monophosphoryl lipid A (MPLA). Control groups included protein alone, MPLA, or PBS. After challenge infection, animals vaccinated with chimeric protein plus MPLA showed a reduction of 73.54% of larval load in the lung compared to control group animals. Animals immunized with chimeric protein plus MPLA also display higher IgG response and a reduction in lung inflammation. Our study highlights how chimeric proteins containing more than one B cell epitope can enhance immune protection against helminthic infection and offer new approaches to the development of Ascaris vaccines.     

Extracellular vesicles released from irradiated neonatal mouse cheek tissue increased cell survival after radiation

Alopecia is one of the common symptoms after high-dose radiation exposure. In our experiments, neonatal mice that received 7 Gy X-ray exhibited defects in overall hair growth, except for their cheeks. This phenomenon might suggest that some substances were secreted and prevented hair follicle loss in the infant tissues around their cheeks after radiation damage. In this study, we focused on exosome-like vesicles (ELV) secreted from cheek skin tissues and back skin tissues, as control, and examined their radiation protective effects on mouse fibroblast cell lines. We observed that ELV from irradiated cheek skin showed protective effects from radiation. Our results suggest that ELV from radiation-exposed cheek skin tissue is one of the secreted factors that prevent hair follicle loss after high-dose radiation.     

Antisense oligodeoxynucleotides against thrombomodulin suppress the cell growth of lung adenocarcinoma cell line A549

Thrombomodulin (TM), an anticoagulant factor on endothelial cells, is known to be expressed in non-endothelial cells as well. In neoplastic cells of lung adenocarcinomas, TM is expressed but its correlation with growth potential has not been studied. As TM expression has a negative correlation with cell proliferation in lung squamous cell carcinomas, we examined its growth effect on lung adenocarcinoma cells of the A549 cell line by inhibiting TM expression with antisense oligodeoxynucleotides (ODN). In the antisense ODN transfected cells, the expression of TM mRNA was decreased to 49% at 12 h and 47% at 24 h, which was in accordance with TM expression at the protein level. By IdU (5-iodo-2'-deoxyuridine) incorporation assay, the growth of A549 cells was found to have decreased to 36% of the control level at 24 h post-transfection. The suppression of cell growth was maintained in a concentration-dependent manner for 48 h after transfection, when the expression of TM started to rebound. In the transfected cells, the G1 phase cell count was reduced to 60.7%, compared with 68.2% in the control transfectants. These results suggest that TM expression may play a suppressive role in the proliferation activity of A549 lung adenocarcinoma cells.     

Hypoxia-ischemic insult in neonatal rats induced slowly progressive brain damage related to memory impairment

The present study was designed to determine potential associations between the brain damage induced by hypoxic-ischemic (HI) insult and spatial learning impairment in an eight-arm radial maze task. We first determined the pathological outcomes after 2, 5, 9, and 17 weeks of recovery following the HI insult. The results show that the brain damage progressed from 2 up to 17 weeks of recovery. To clarify the time course of the brain damage changes, we investigated the histological changes of the same individual with magnetic resonance imaging (MRI) after 5, 9, and 57 weeks of recovery following the HI insult. The MRI changes were similar to the histological changes, and the brain damages were exacerbated in the contralateral hemisphere after 57 weeks of recovery following the HI insult. To investigate whether alteration in brain function was correlated with MRI and histological changes, the rats were made to find their way through an eight-arm radial maze was performed at either 7th or 16th weeks of recovery. According to the results, the spatial learning impairments of rats in the maze starting at 16 weeks of recovery were more severe than those at 7 weeks of recovery, indicating that the impairments were progressive and depended on the degree of brain damage. The results of the present study are the first demonstration that the evolutional and specific brain damage following the HI insult is slowly and progressively exacerbated to the contralateral hemisphere and rats who experience the HI are at risk for showing a late impairment of brain function.     

Reduction of cell proliferative activities of gastric stump adenomatous hyperplasias after bile reflux diversion in rats

Previously we reported the majority of lesions induced by bilereflux, in the absence of chemical carcinogens, in the rat remnantstomach to consist primarily of gastric type and secondarilyof intestinal type cells, and that they are reversible afterdiversion of bile reflux. The present study was designed toevaluate changes in proliferative activities in cells of eachtype under these conditions. The frequency of adenomatous hyperplasia(AH) induced in the gastric stump mucosa by duodenal contentreflux after Billroth II partial gastrectomy (BII) increaseduntil the 54th week of the experiment. Roux-en-Y (RY) surgicalprocedure which prevents duodenal reflux performed at the 24thor 36th week after BII led to a decrease in AH. Cell contentof the lesions was analyzed using routine H&E staining,immunohistochemical staining for pepsinogen isoenzyme 1 andhistochemical procedures for mucins (paradoxical concanavalinA, galactose oxidase Schiff and sialidase galactose oxidaseSchiff reactions) and proliferation in each compartment evaluatedby an immunohistochemical method using bromodeoxyuridine (BrdU)and a monoclonal antibody against BrdU. At the 54th week thenumber of BrdU-labeled cells per normal pyloric column was significantly(P < 0.05) increased to 10.63/pit after the BII operation,while it diminished to 5.23/pit after RY diversion, this beingthe same level as with the RY procedure alone. AH maintaineda high rate of BrdU incorporation at 12.7% after BII operation,which was also significantly reduced (P < 0.01) to 7.0% bythe RY surgery. The intestinal type cell showed highest (22.2%),the surface mucous type cell showed the next (16.5%) and thepyloric gland type cell showed lowest (5.2%) BrdU labeling indicesafter BII operation. All the cell types in AH showed similarproportional decreases in BrdU incorporation after RY diversion.Thus surgical intervention reverses the cell proliferation causedby bile reflux in the gastric stump.     

Hip fracture mortality and morbidity in Switzerland and Japan: A cross-cultural comparison

Summary Based on national mortality data, the frequency of hip fractures in elderly people was compared between Switzerland and Japan. Age-adjusted annual incidence rates per 100 000 population estimated for Swiss persons over 60 years were around 150 and 200 in males and around 450 in females, while for the Japanese they were only 132 in males and 285 in females. Age-adjusted death rates from hip fracture for the Swiss over 60 were 20.0 in males and 28.9 in females, while for the Japanese they were only 1.6 in males and 2.7 in females. The inclination of the age-dependent slope in hip fracture mortality rates was substantially the same in both countries, but there was a lag time of approximately 10 years in Japan. Remarkably, the proportion of deaths due to falls among all accidental deaths was several times greater in both sexes for the Swiss than for the Japanese. This differential might be an important underlying reason for the observed difference between death rates of hip fracture in Switzerland and Japan. Other known behavioral risk factors for hip fracture such as diet, exercise, estrogen use etc. are unlikely to explain the observed difference in hip fracture mortality and morbidity between Switzerland and Japan. However, given the doubts on the reliability and thus comparability of the available data on mortality and morbidity, the present findings should be regarded as preliminary. In conclusion, we believe that the unexplained and large difference in the burden of hip fracture between Switzerland and Japan merits further studies, including new aetiological hypotheses.

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Zusammenfassung Gestützt auf nationale Sterbedaten wird die Häufigkeit von Hüftfrakturen bei Betagten in der Schweiz und Japan verglichen. Alterskorrigierte jährliche Inzidenzraten (bezogen auf 100 000 Einwohner) bezifferten sich bei den Schweizer Personen über 60 Jahren auf ca. 150–200 bei den Männern sowie ca. 450 bei den Frauen, während bei den Japanern die entsprechenden Inzidenzen lediglich 132 bei den Männern und 285 bei den Frauen betrugen. Die alterskorrigierte durch Hüftfrakturen bedinte Mortalität (pro 100000) betrug bei den Schweizern über 60 Jahren 20,0 bei den Männern und 28,9 bei den Frauen, während bei den Japanern die entsprechenden Werte bei 1,6 für Männer und 2,7 für Frauen lagen. Die Gerade, die das Verhältnis zwischen Alter und Hüftfraktur-Mortalität charakterisiert, zeigte in beiden Ländern ungefähr die gleiche Steigung, war in Japan jedoch um ca. 10 Jahre rechtsverschoben. Bemerkenswerterweise war der Anteil sturzbedingter Todesfälle unter allen unfallbedingten Todesfällen bei beiden Geschlechtern in der Schweiz wesentlich höher als in Japan. Dieser Unterschied könnte eine wichtige, zurgrundeliegende Ursache für die Differenz in der Hüftfrakturmortalität zwischen der Schweiz und Japan darstellen. Andere verhaltensabhängige Risikofaktoren für Hüftfraktur wie Ernährung, körperliche Bewegung, Oestrogenzufuhr usw. vermögen die beobachteten Unterschiede in der Mortalität und Morbidität an Hüftfraktur zwischen der Schweiz und Japan kaum zu erklären Angesichts der ungewissen Reliabilität und Vergleichbarkeit der zur Verfügung stehenden Daten müssen die vorliegenden Ergebnisse allerdings mit Vorsicht interpretiert werden. Zusammenfassend glauben wir, dass der grosse und weitgehend unerklärte schweizerisch-japanische Unterschied im Auftreten von Hüftfrakturen weiter abgeklärt werden sollte, unter Einschluss neuer ätiologischer Hypothesen.

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Résumé Basée sur les données de mortalité nationales, la fréquence des fractures de hanche des personnes âgées est comparée entre la Suisse et le Japon. Les taux d'incidence annuels corrigés pour l'effet de l'âge chez les personnes suisses âgées de plus de 60 ans sont d'environ 150–200 chez les hommes (par rapport à 100 000 habitants), ainsi qu'environ 450 chez les femmes, tandis qu'au Japon les incidences correspondantes s'élèvent à 132 chez les hommes et 285 chez les femmes. La mortalité des fractures de hanche, corrigée pour l'effet de l'âge s'élève chez les Suisses âgés de plus de 60 ans à 20,0 (par 100 000) chez les hommes et à 28,9 chez les femmes, alors que chez les Japonais les taux correspondants sont 1,6 chez les hommes et 2,7 chez les femmes. La proportion de décès faisant suite à des chutes parmi l'ensemble des accidents mortels est remarquablement plus élevée en Suisse qu'au Japon, pour les femmes comme pour les hommes. Cette différence pourrait expliquer le taux élvé de décès suite à une fracture de hanche observé en Suisse. D'autres facteurs de risque pour la fracture de hanche liés au style de vie ne sont apparemment pas en mesure d'expliquer les différences de mortalité et de morbidité par fracture de hanche observées entre la Suisse et le Japon. Face aux doutes qui concernent la fiabilité et la comparabilité des données à disposition, ces résultats doivent être interprétés avec prudence. Toutefois, nous pensons que la différence substantielle des taux de fractures de hanche entre Suisse et Japon, qui reste inexpliquée, devrait être examinée plus en détail, également en ce qui concerne de nouvelles hypothèses étiologiques.

     

CD98 regulates the phosphorylation of HER2 and a bispecific anti-HER2/CD98 antibody inhibits the growth signal of human breast cancer cells

Human epidermal growth factor receptor (HER) family proteins are currently major targets of therapeutic monoclonal antibodies against various epithelial cancers. However, the resistance of cancer cells to HER family-targeted therapies, which may be caused by cancer heterogeneity and persistent HER phosphorylation, often reduces overall therapeutic effects. We herein showed that a newly discovered molecular complex between CD98 and HER2 affected HER function and cancer cell growth. The immunoprecipitation of the HER2 or HER3 protein from lysates of SKBR3 breast cancer (BrCa) cells revealed the HER2-CD98 or HER3-CD98 complex. The knockdown of CD98 by small interfering RNAs inhibited the phosphorylation of HER2 in SKBR3 cells. A bispecific antibody (BsAb) that recognized the HER2 and CD98 proteins was constructed from a humanized anti-HER2 (SER4) IgG and an anti-CD98 (HBJ127) single chain variable fragment, and this BsAb significantly inhibited the cell growth of SKBR3 cells. Prior to the inhibition of AKT phosphorylation, BsAb inhibited the phosphorylation of HER2, however, significant inhibition of HER2 phosphorylation was not observed in anti-HER2 pertuzumab, trastuzumab, SER4 or anti-CD98 HBJ127 in SKBR3 cells. The dual targeting of HER2 and CD98 has potential as a new therapeutic strategy for BrCa.     

A case of dermatofibrosarcoma protuberans in the skin over the breast

Dermatofibrosarcoma protuberans (DFSP) is a slow-growing but locally aggressive, fibrous tumor that has a high rate of local recurrence after surgical resection. This tumor occurs most commonly in the trunk and proximal extremities. In this report we present a case of dermatofibrosarcoma protuberans in the skin over the breast which was re-excised after pathological diagnosis, considering cosmetic aspects. Only three other cases of dermatofibrosarcoma protuberans of the anterior chest wall have been encountered in our hospital, and all of these cases were male. The presence of this tumor in the skin over the breast appears to be rare in females. Careful complete resection is recommended for this type of tumor.