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1.
Anticancer Res ; 40(5): 2881-2887, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366438

RESUMO

BACKGROUND/AIM: This study evaluated the prognostic significance of preoperative neutrophil-to-lymphocyte ratio (NLR) and CD8+ tumor-infiltrating lymphocytes (TILs), and whether preoperative NLR was associated with CD8+ TILs in biliary tract cancers (BTCs). PATIENTS AND METHODS: A total of 154 patients with BTCs who underwent surgery were enrolled in this study. We obtained neutrophil and lymphocyte counts, and calculated NLR from preoperative peripheral blood samples. CD8+ TILs were identified by immunohistochemical staining. RESULTS: The overall survival (OS) and recurrence-free survival (RFS) of patients with high NLR were shorter than those with low NLR. The OS and RFS of patients with high CD8+ TILs were longer than those with low CD8+ TILs. Preoperative NLR and CD8+ TILs were negatively correlated. CONCLUSION: NLR and CD8+ TILs were associated with OS and RFS in BTCs. NLR can predict CD8+ TILs infiltrating the cancer microenvironment.

2.
Intern Med ; 59(9): 1119-1124, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32378653

RESUMO

Objective Cardiovascular disease increases the risk of maternal mortality. This study examined the risk factors for cardiovascular events in pregnant women with cardiovascular disease. Methods This was a case-control study conducted in 2 phases at Japanese maternal and fetal care centers. The primary survey, using an interviewer-administered questionnaire, investigated whether the institutions had managed pregnant women with cardiovascular disease from April 2014 to March 2016. From 424 individual facilities surveyed, 135 facilities were found to have experience in managing pregnant women. In the secondary survey, the 135 institutions were asked to complete a web-based questionnaire, which collected detailed clinical information about cases, including cardiovascular disease, cardiovascular events, maternal background, and the perinatal outcome. Results Information on 302 pregnant women with cardiovascular disease was collected. None of the 302 patients died. There were 25 women with cardiovascular events (cardiovascular event group) and 277 women without cardiovascular events (non-cardiovascular event group); the two groups were compared. No significant differences were found in the perinatal outcomes. Medication use before pregnancy was identified as a risk factor for cardiovascular events (adjusted odds ratio, 23.28; 95% confidence interval, 8.15-66.47; p<0.001). In pregnant women with cardiovascular disease, New York Heart Association (NYHA) functional class II or III before pregnancy was associated with a higher risk of cardiovascular events in comparison to NYHA functional class I (p<0.001 for both). Conclusion Medication use before pregnancy and NYHA functional class >I were risk factors for cardiovascular events in pregnant women with cardiovascular disease.

3.
Anticancer Res ; 40(5): 2637-2644, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32366408

RESUMO

BACKGROUND/AIM: There is rapid progression and widespread use of patient-derived tumor xenografts (PDX) in translational pancreatic cancer research. This study aimed to establish a liver transplant PDX model using cryopreserved primary pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: Primary PDAC from 10 patients were cryopreserved and transplanted into immunodeficient mice using the liver pocket method. H&E staining and immunohistochemical staining, such as Ki-67, p53, Smad4, and MUC1 were used to evaluate engraftment and histological similarities. RESULTS: Patient-derived xenograft placement was successful in six cases (60%), and 10 mice (33.3%). The Ki-67 index of primary PDAC and the cryopreservation duration were significantly related to successful engraftment (p=0.003 and p=0.007, respectively). CONCLUSION: In this study, we succeeded in establishing a liver transplant PDX mouse model as a preclinical platform. The successful engraftment was affected by the cryopreservation duration and could be detected by the Ki-67 index.


Assuntos
Carcinoma Ductal Pancreático/patologia , Criopreservação , Transplante de Fígado , Neoplasias Pancreáticas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade
4.
J Clin Med ; 9(5)2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32413997

RESUMO

To assess the long-term effects of tadalafil, a therapeutic agent for fetal growth restriction (FGR), we evaluated the developmental progress of 1.5-year-old infants whose mothers had taken tadalafil during pregnancy. Twenty-four infants were assessed. We evaluated infant body weight, height, and head circumference, and performed the Kyoto Scale of Psychological Development (KSPD) test, a standardized developmental assessment covering Postural-Motor (P-M), Cognitive-Adaptive (C-A), and Language-Social (L-S) functions. The sum score was converted to a developmental quotient (DQ). The mean gestational week of the included cases was 36.1 (29-39) weeks, and the mean birth weight was 1841 (874-2646) g. Twenty-one and 20 out of the 24 cases, respectively, attained body weight and height similar to those of age-matched normal infants (within the 3rd percentile); all cases caught up in head circumference. KSPD was performed for 18 cases at 1.5 years of corrected age. The mean DQ scores were 87 (in total): 82 in P-M, 90 in C-A, and 88 in L-S. The total DQ score in one case (5.6%) was less than 70, and ranged from 70 to 85 in five cases (27.7%), and was more than 85 in 11 cases (61.1%). The growth and development of infants born of tadalafil-treated mothers seem to show good progress at a corrected age of 1.5 years.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32451902

RESUMO

This study evaluated the occurrence of PPCPs in Cau River (Vietnam). Surface water and sediment samples were collected to determine PPCP concentrations. The analysis results showed the presence of 36 out of 56 investigated PPCPs in samples. The total concentration of PPCPs in water samples ranged from 8.21 to 529 ng/L and the value observed in sediment was from 17.4 to 172.8 µg/kg. Along the Cau River, there was a trend of accumulation of PPCPs at the downstream. The highest level of PPCP was observed after the river flows through Thai Nguyen and Bac Ninh provinces. Among detected PPCPs, the ones detected with high frequency (over 70%) and high concentration were caffeine, sulfamethoxazole, and lincomycin in water and triclocarban, levofloxacin, and griseofulvin in sediment. The water-sediment partition coefficient (Kd) was estimated to explore the fate of PPCP in the river, and the observed Kd mean values for lincomycin, sulfamethoxazole, and griseofulvin were 223.0, 7.6, and 997.0 kg/L, respectively. Risk assessment was initially conducted by applying a semi-quantitative assessment risk quotient (RQ); the potential ecological risk to the aquatic organism of PPCPs posed a moderate risk.

7.
Bioorg Med Chem ; : 115531, 2020 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-32386953

RESUMO

The M3 muscarinic acetylcholine receptor (mAChR) is a member of the family of mAChRs, which are associated with a variety of physiological functions including the contraction of various smooth muscle tissues, stimulation of glandular secretion, and regulation of a range of cholinergic processes in the central nerve system. We report here the discovery and a comprehensive structure--activity relationships (SARs) study of novel positive allosteric modulators (PAMs) of the M3 mAChR through a high throughput screening (HTS) campaign. Compound 9 exhibited potent in vitro PAM activity towards the M3 mAChR and significant enhancement of muscle contraction in a concentration-dependent manner when applied to isolated smooth muscle strips of rat bladder. Compound 9 also showed excellent subtype selectivity over other subtypes of mAChRs including M1, M2, and M4 mAChRs, and moderate selectivity over the M5 mAChR, indicating that compound 9 is an M3-preferring M3/M5 dual PAM. Moreover, compound 9 displayed acceptable pharmacokinetics profiles after oral dosing to rats. These results suggest that compound 9 may be a promising chemical probe for the M3 mAChR for further investigation of its pharmacological function both in vitro and in vivo.

8.
Taiwan J Obstet Gynecol ; 59(3): 356-360, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32416879

RESUMO

OBJECTIVE: This study aimed to evaluate whether the Edinburgh Postnatal Depression Scale (EPDS) score predicts the occurrence of premenstrual syndrome (PMS) and premenstrual dysphoric disorder (PMDD) after delivery. MATERIALS AND METHODS: The women in this study were registered at 35-36 weeks of pregnancy at Mie University Hospital from 2013 to 2015. We prospectively divided the puerperants into those with an EPDS score ≥9 (the high-EPDS group) and those with an EPDS score <9 (the low-EPDS group) at 1 month postpartum. We compared the incidence rate of severe PMS and PMDD between both groups at 1 year after delivery. RESULTS: Of 200 registered cases, 178 (89.0%) did not experience severe PMS or PMDD before pregnancy. Among them, 21 were in the high-EPDS group, and 89 in the low-EPDS group. Four of the 21 women (19.0%) in the high-EPDS group and five of the 89 (5.6%) in the low-EPDS group had severe PMS or PMDD at 1 year after delivery. The incidence rate of severe PMS or PMDD in the high-EPDS group was higher than that in the low-EPDS group (p = 0.07). CONCLUSIONS: The novel finding of this study is that the EPDS may predict the occurrence of severe PMS/PMDD after delivery. The EPDS will contribute to the early detection of these diseases and to improving the quality of life of the patients by allowing treatment initiation at an early stage.

9.
Int J Oncol ; 57(1): 171-182, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32319601

RESUMO

Tertiary lymphoid structures (TLSs), which consist of B cells, T cells, follicular dendritic cells and high endothelial venules, have recently been found to be associated with effective antitumor immune responses in patients with cancer. Tumor­infiltrating T cells and B cells have each been demonstrated to be associated with survival in patients with cancer. We hypothesized that TLSs, an assembly of immune cells, may be important for the initiation and/or maintenance of T cell and B cell responses against tumors. The aim of the present study was to examine the cellular mechanism of B cells in TLSs within gastric cancer and to understand the antitumor immune response of TLSs. Each B cell subset in a tumor was examined using flow cytometry to evaluate B cell differentiation and the functional status of B cells. In addition, B cell clonality was investigated by analyzing the B cell antigen receptor gene using PCR, and the function and formation/maintenance of TLSs were evaluated using reverse transcription­quantitative PCR. Tumor­infiltrating B cells were more differentiated compared with that in distant non­tumor tissues and tumor­draining lymph nodes. The PCR results revealed specific BCR gene expression in tumor­infiltrating B cells. The expression of co­stimulatory factors, CD80 and CD86, was observed, in addition to the constantly expressed major histocompatibility complex molecules (HLA­ABC and HLA­DR). CD70 was expressed in addition to CD27 in both CD20+ B cells and CD8+ T cells, indicating that these factors are activated together through their interaction. The mRNA expression levels of CCL21, CXCL13, PD­L1, perforin and granzyme B in TLSs was significantly higher compared with that in non­TLSs. The majority of tumor­infiltrating B cells in gastric cancer exist in the form of TLSs around the tumor and have been antigen­sensitized and differentiated, and proliferated in TLSs but not in the lymph nodes. In addition, B cells in TLSs might primarily function as antigen­presenting cells and be associated with the induction of cytotoxic T cells.

10.
Sci Rep ; 10(1): 5206, 2020 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-32251356

RESUMO

Groundwater through hand-operated tubewell (a type of water well) tapping is the main source of drinking water in Bangladesh. This study investigated iron and manganese concentration in groundwater across Jashore district-one of the worst arsenic contaminated area in Bangladesh. One working tubewell that had been tested previously for arsenic and marked safe (green) was selected from each unions of the district. Results revealed that approximately 73% and 87% of groundwater samples exceeded the limits for iron and manganese in Bangladesh drinking water, respectively. Additionally, spatial distribution of iron and manganese indicate that only 5% of the total surface area of groundwater is covered by safe level of iron and manganese. Human health risk due to ingestion of iron and manganese through drinking water was evaluated using hazard quotients (HQ) for adults and children. The result of the health risk assessment revealed that the non-carcinogenic health risks due to ingestion of iron (HQ up to 1.446 for adults and 0.590 for children) and manganese (HQ up to 2.459 for adults and 1.004 for children) contaminated groundwater are much higher among adults than children. On the basis of occurrences, spatial distribution and health risk assessment results, the area can be categorized as a high-risk zone for iron and manganese-related problems and needs special attention in order to protect public health of local residents.

11.
Biol Pharm Bull ; 43(5): 848-858, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32161223

RESUMO

Kawasaki disease (KD) is an inflammatory disease that was identified by Professor Tomisaku Kawasaki in 1961. Candida albicans-derived substances, such as the hot water extract of C. albicans (CADS) and Candida water-soluble fraction (CAWS), induced coronary vasculitis similar to KD in mice. An increasing proportion of deep-seated candidiasis cases are caused by non-albicans Candida and are often resistant to antifungal drugs. We herein investigated whether the hot water extract of C. krusei, inherently resistant to fluconazole, induces vasculitis in mice. Three strains of C. krusei, NBRC1395, NBRC1162, and NBRC10737, were cultured in natural (Y) and chemically defined (C) media and cell wall mannoprotein (MN) fractions were prepared by autoclaving cells (CKY1395MN, CKC1395MN, CKY1162MN, CKC1162MN, CKY10737MN, and CKC10737MN). All MN fractions reacted strongly with Concanavalin A (Con A) and dectin-2 and induced anaphylactoid shock in ICR mice. MNs induced severe coronary vasculitis in DBA/2 mice, resulting in cardiac hypertrophy. MNs also induced coronary vasculitis in C57Bl/6 mice. These results suggest that the MNs of non-albicans Candida, such as C. krusei, induce similar toxicity to those of C. albicans.

12.
Rinsho Ketsueki ; 61(2): 116-121, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-32147610

RESUMO

An 85-year-old man presented with right eye ptosis and visual abnormalities. Due to a lack of abnormal findings on plain magnetic resonance imaging (MRI) and laboratory examination, prednisolone therapy was initiated, and ocular myasthenia gravis and ocular symptoms subjectively improved. However, anorexia and conscious disorder appeared during the same period, and he was hospitalized for scrutiny. After admission, left eye adduction disorder and bilateral abduction nerve paralysis were also observed. Enhanced MRI revealed cranial nerve and leptomeninx enhancement. Subsequently, the patient developed seizures and died on the 10th day of hospitalization without being diagnosed. An autopsy revealed infiltration of B-cell lymphoma cells into the subarachnoid space, particularly in the parietal lobe. Similar infiltration was observed in the cerebellum, brainstem, spinal cord, and bilateral oculomotor nerve. Primary leptomeningeal lymphoma is a rare form of primary central nervous system lymphoma without simultaneous parenchymal brain lesions. Clinicians should be aware of this form of lymphoma and carefully monitor its possible occurrence, even when patients are already being treated for other neurological diseases.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma de Células B , Oftalmoplegia , Idoso de 80 Anos ou mais , Humanos , Imagem por Ressonância Magnética , Masculino
13.
J Phys Chem Lett ; : 2086-2091, 2020 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-32101434

RESUMO

We studied the alignment changes of polymer-capped gold nanorods (GNRs@PS) under an applied electric field by visible-near-infrared absorption and small-angle X-ray scattering (SAXS) measurements. Monodispersed GNRs with an aspect ratio of 4.0 were produced by the seed-mediated growth method using cetyltrimethylammonium bromide and sodium oleate binary surfactants. We investigated the phase transition between the ordered structure of GNRs@PS induced by the external electric field. At appropriate field strengths (>3 V/µm), the SAXS profiles of GNRs@PS showed a smectic ordered structure. Increasing the electric field strength densified the ordered structure and greatly increased the Raman signals (the 298 and 445 cm-1 bands) of the carbon tetrachloride (solvent) between the GNRs@PS. The insights gained are potentially applicable to catalysts, future displays, optical filters, and data storage devices.

14.
Anticancer Res ; 40(2): 1147-1152, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32014967

RESUMO

BACKGROUND: Neoadjuvant treatment with imatinib mesylate (IM) has not been established for gastrointestinal stromal tumor (GIST). A case of a giant gastric GIST that was radically resected following neoadjuvant therapy with IM is reported. CASE REPORT: A 71-year-old woman with abdominal distension was referred to our hospital for treatment. Contrast-enhanced computed tomography showed a large (>30 cm), heterogeneous mass, with dilated vessels around the tumor. The diagnosis was a gastric GIST by endoscopic ultrasound-fine needle aspiration, and neoadjuvant therapy with 400 mg IM daily was started. Radical surgery was performed after 13 months. Since the tumor was not invasive, complete resection by partial gastrectomy was achieved without the need for combined resection of other organs. The patient remains alive without recurrence 12 months after surgery. CONCLUSION: A giant GIST, larger than 30 cm in size, is quite rare. Neoadjuvant IM treatment should be considered in the management of large GISTs.


Assuntos
Antineoplásicos/uso terapêutico , Gastrectomia , Tumores do Estroma Gastrointestinal/diagnóstico , Tumores do Estroma Gastrointestinal/terapia , Mesilato de Imatinib/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Biópsia , Terapia Combinada , Feminino , Gastrectomia/métodos , Humanos , Mesilato de Imatinib/administração & dosagem , Mesilato de Imatinib/efeitos adversos , Terapia Neoadjuvante , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Carga Tumoral
15.
J Appl Toxicol ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32077112

RESUMO

Pharmaceuticals are widely detected in aquatic environments, and their potential risks to aquatic species are of concern because they are designed to be biologically active. Here, we used an in vitro assay, called the transforming growth factor α shedding assay, to measure the biological activities of G protein-coupled receptor (GPCR)-acting pharmaceuticals present in river water and effluents from municipal wastewater treatment plants (WWTPs) in Japan from 2014 to 2016. Antagonistic activities against angiotensin (AT1), dopamine (D2), adrenergic (ß1), acetylcholine (M1) and histamine (H1) receptors were detected in river water, and were stronger downstream than upstream owing to effluent from WWTPs along the river. Ozonation at one WWTP reduced these activities. Concentrations of sulpiride (D2 antagonist) could explain 73% of antagonistic activities against the D2 receptor; those of metoprolol, atenolol and propranolol (ß1 antagonists) could explain 16% of activities against the ß1 receptor; and those of pirenzepine (M1 antagonist) could explain 15% of activities against the M1 receptor. Therefore, other receptor antagonists also occur. GPCR-acting pharmaceuticals should be given more attention in environmental monitoring and toxicity testing.

17.
Pediatr Int ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32048772

RESUMO

PURPOSE: The aim of this study was to determine the frequency and nature of pediatric blunt chest-abdominal injuries (BCAIs) and to summarize the management of BCAIs, ranging from non-operative management (NOM) with or without angioembolization (AE) to surgical treatment. METHODS: This retrospective study included patients hospitalized for BCAIs in our hospital from January 1996 to December 2017. The age, injury pattern, organs of injury, outcome, and treatment were summarized. RESULTS: One hundred and thirty-two cases (98 males, 34 females, mean age 7.68 years; range 1-15 years) were summarized. Sixty patients were involved in motor-vehicle traffic injuries; 16 single bicycle injuries; 33, falls; 11, sports; 6, assault; 3, abuse; and 4, others. There were no injured organs in 31 cases, while there were 130 injured organs in 101 cases, including the liver (42), spleen (35), lung (23), kidney (13), intestine (10), pancreas (5), and adrenal gland (2). Angiography (AG) was performed in 20 cases, and NOM with AE was performed in 16 patients, including 17 organs (liver injury 9, splenic injury 5, and kidney injury 4). Surgical treatment was performed in 8 cases (splenic injury in one, pancreas injury in one, and intestinal injury in six). NOM without AE was performed in the other cases. CONCLUSIONS: The management of organ injury must keep into consideration the integrated bleeding management. It is recommended that children with severe organ injury were treated in dedicated trauma centers in which AE is available.

19.
PLoS One ; 15(1): e0225958, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31940352

RESUMO

BACKGROUND: Peritoneal recurrence is one of the most frequent recurrent diseases in gastric cancer. Although the exposure of cancer cells to the serosal surface is considered a common risk factor for peritoneal recurrence, there are some cases of peritoneal recurrence without infiltration to the serosal surface even after curative surgery. This study sought to clarify the risk factors of peritoneal recurrence in the absence of invasion to the serosal surface. MATERIALS AND METHODS: Ninety-six patients with gastric cancer who underwent curative surgery were enrolled. In all 96 cases, the depth of tumor invasion was subserosal (T3). The microscopic distance from the tumor invasion front to the serosa (DIFS) was measured using tissue slides by H&E staining and pan-cytokeratin staining. E-cadherin expression was evaluated by immunohistochemical staining. RESULTS: Among the 96 patients, 16 developed peritoneal recurrence after curative surgery. The DIFS of the tumors with peritoneal recurrence (156±220 µm) was significantly shorter (p = 0.011) than that without peritoneal recurrence (360±478 µm). Peritoneal recurrence was significantly correlated with DIFS ≤234 µm (p = 0.023), but not with E-cadherin expression. The prognosis of DIFS ≤234 µm was significantly poorer than that of DIFS >234 µm (log rank, p = 0.007). A multivariate analysis of the patients' five-year overall survival revealed that DIFS ≤234 µm and lymph node metastasis were significantly correlated with survival (p = 0.005, p = 0.032, respectively). CONCLUSION: The measurement of the DIFS might be useful for the prediction of peritoneal recurrence in T3-gastric cancer patients after curative surgery.


Assuntos
Neoplasias Peritoneais/diagnóstico , Neoplasias Peritoneais/patologia , Membrana Serosa/patologia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Idoso , Caderinas/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Invasividade Neoplásica , Estadiamento de Neoplasias , Prognóstico , Recidiva , Fatores de Risco , Neoplasias Gástricas/metabolismo , Análise de Sobrevida
20.
J Chemother ; 32(2): 83-87, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31957595

RESUMO

Several reports have investigated relationships between epidermal growth factor receptor (EGFR) mutations and the efficacy of EGFR-tyrosine kinase inhibitors (TKIs) in EGFR-mutant non-small cell lung cancer; however, there have been insufficient analyses of relationships between EGFR mutations and adverse reactions. This study investigated the relationships between EGFR mutations and skin rash. We first compared skin rash grades between different mutations, then tested factors possibly affecting skin rash by multivariate analysis. The main outcome measure was the significant difference in incidence of skin rash between each group with different mutations. Our study suggested that the risk of skin rash is low in patients with exon 19 deletion mutations who are taking EGFR-TKIs, whereas it is high in those with exon 21 point mutations. These results will be useful indicators for instructions regarding daily examinations, skin care, and use of oral antibiotics or topical steroids in patients taking EGFR-TKIs with skin rash.

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