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1.
Am J Alzheimers Dis Other Demen ; 35: 1533317519899546, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32162525

RESUMO

Alzheimer disease (AD) may develop after the onset of type 2 diabetes mellitus (T2DM), and the risk of AD may depend on the antidiabetic drug administered. We compared the risk of AD among 66 085 patients (≥ 65 years) with T2DM (1250 having concomitant AD) who had been administered antidiabetic drug monotherapy for T2DM who had voluntarily reported themselves in the Food and Drug Administration Adverse Event Reporting System. The risk of AD from the use of different antidiabetic drug monotherapies compared to that of metformin monotherapy was assessed by logistic regression. Rosiglitazone (adjusted reporting odds ratio [aROR] = 0.11; 95% confidence interval [CI]: 0.07-0.17; P < .001), exenatide (aROR = 0.22; 95% CI: 0.11-0.37; P < .001), liraglutide (aROR = 0.36; 95% CI: 0.19-0.62; P < .001), dulaglutide (aROR = 0.39; 95% CI: 0.17-0.77; P = .014), and sitagliptin (aROR = 0.75; 95% CI: 0.60-0.93; P = .011) were found to have a significantly lower associated risk of AD than that of metformin. Therefore, the administration of glucagon-like peptide 1 receptor agonists and rosiglitazone may reduce the risk of AD in patients with T2DM.

2.
Intern Med ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32132337

RESUMO

A 64-year-old woman developed symptoms of vomiting and tonic-clonic convulsions 9.5 h after eating 50 roasted Ginkgo biloba seeds with 100 g of alcohol. The intravenous administration of pyridoxal phosphate effectively improved the symptoms. Blood samples were collected and stored over 35 h. The assessment of 4'-O-methylpyridoxine and vitamin B6 vitamers indicated high levels of both, but the pyridoxal phosphate levels were low during the acute stage. These results suggest that 4'-O-methylpyridoxine inhibits the transformation of vitamin B6 analogues to the active form, pyridoxal phosphate. In our case, alcohol may have extended the period until ginkgo intoxication appeared.

3.
No Shinkei Geka ; 48(3): 237-244, 2020 Mar.
Artigo em Japonês | MEDLINE | ID: mdl-32201393

RESUMO

Primary cerebellar glioblastoma is a rare disease that accounts for 0.4-3.4% of glioblastoma multiforme(GBM)cases. The clinicopathological characteristics and prognosis of primary cerebellar GBM are not well understood due to its rarity and the lack of an established treatment strategy. To elucidate the prognostic factors and dissemination pattern, we retrospectively assessed four cases of cerebellar GBM that we treated between 2003 and 2013. All cases involved men, and the age range was 53 to 76 years(median 69.5 years);each patient underwent surgical removal and received adjuvant chemotherapy or radiotherapy. Every cerebellar GBM patient developed intrathecal dissemination at every stage of cerebellar GBM. Two patients had spinal metastases with tumor recurrence, and no patient had brain stem invasion. IDH1 mutation and MGMT expression were both negative in three cases. The median overall survival of cerebellar GBM patients was 13.8 years, and the median progression-free survival was 5.5 years, which is similar to that reported in previous reports-and similar in terms of results-for supratentorial GBM treated at the same time at our institution. In conclusion, the prognosis of cerebellar GBM appears to be similar to that of supratentorial GBM;however, the pattern of tumor progression, such as intrathecal dissemination, is different. Craniospinal irradiation on cerebellar GBM should be carefully considered with frequent follow-up by whole spine survey using MRI.

4.
Viruses ; 12(3)2020 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-32121094

RESUMO

Japanese encephalitis (JE) remains a public health concern in several countries, and the Culex mosquito plays a central role in its transmission cycle. Culex mosquitoes harbor a wide range of viruses, including insect-specific viruses (ISVs), and can transmit a variety of arthropod-borne viruses (arboviruses) that cause human and animal diseases. The current trend of studies displays enhanced efforts to characterize the mosquito virome through bulk RNA sequencing due to possible arbovirus-ISV interactions; however, the extent of viral diversity in the mosquito taxon is still poorly understood, particularly in some disease vectors. In this study, arboviral screening and RNA virome analysis of Culex tritaeniorhynchus and C. pseudovishnui, which are part of the Culex vishnui subgroup mosquitoes, were performed. Results from these two mosquito species, known as the major vectors of JE virus (JEV) in Asia, collected in three prefectures in Japan were also compared with the sympatric species C. inatomii. A total of 27 viruses, including JEV, were detected from these Culex mosquitoes. Molecular and phylogenetic analyses of the detected viruses classified 15 of the 27 viruses as novel species, notably belonging to the Flaviviridae, Rhabdoviridae, Totiviridae, and Iflaviridae families. The successful isolation of JEV genotype I confirmed its continuous presence in Japan, suggesting the need for periodic surveillance. Aside from JEV, this study has also reported the diversity of the RNA virome of disease vectors and broadened the knowledge on mosquito virome profiles containing both arbovirus and ISV. Mosquito taxon seemed to contribute largely to the virome structure (e.g., virome composition, diversity, and abundance) as opposed to the geographical location of the mosquito species. This study therefore offers notable insights into the ecology and evolution of each identified virus and viral family. To the authors' knowledge, this is the first study to characterize the viromes of the major JE vectors in Japan.

5.
Ann Surg Oncol ; 2020 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-32052303

RESUMO

BACKGROUND: We aimed to clarify the role of potassium voltage-gated channel subfamily J member 15 (KCNJ15) in esophageal squamous cell carcinoma (ESCC) cells and its potential as a prognosticator in ESCC patients. METHODS: KCNJ15 transcription levels were evaluated in 13 ESCC cell lines and polymerase chain reaction (PCR) array analysis was conducted to detect coordinately expressed genes with KCNJ15. The biological functions of KCNJ15 in cell invasion, proliferation, migration, and adhesion were validated through small interfering RNA-mediated knockdown experiments. Cell proliferation was further evaluated through the forced expression experiment. KCNJ15 expression was detected in 200 ESCC tissues by quantitative real-time reverse transcription PCR (qRT-PCR) and analyzed in 64 representative tissues by immunohistochemistry. Correlations between KCNJ15 expression levels and clinicopathological features were also analyzed. RESULTS: The KCNJ15 expression levels varied widely in ESCC cell lines and correlated with COL3A1, JAG1, and F11R. Knockdown of KCNJ15 expression significantly repressed cell invasion, proliferation, and migration of ESCC cells in vitro. Furthermore, overexpression of KCNJ15 resulted in increased cell proliferation. Patients were stratified using the cut-off value of KCNJ15 messenger RNA (mRNA) levels in 200 ESCC tissues using receiver operating characteristic curve analysis; the high KCNJ15 expression group had significantly shorter overall and disease-free survival times. In multivariable analysis, high expression of KCNJ15 was identified as an independent poor prognostic factor. Staining intensity of in situ KCNJ15 protein expression tended to be associated with KCNJ15 mRNA expression levels. CONCLUSIONS: KCNJ15 is involved in aggressive tumor phenotypes of ESCC cells and its tissue expression levels may be useful as a prognosticator of patients with ESCC.

6.
Viruses ; 12(2)2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32012771

RESUMO

Entomological surveillance is one of the tools used in monitoring and controlling vector-borne diseases. However, the use of entomological surveillance for arboviral infection vector control is often dependent on finding infected individuals. Although this method may suffice in highly endemic areas, it is not as effective in controlling the spread of diseases in low endemic and non-endemic areas. In this study, we examined the efficiency of using entomological markers to assess the status and risk of arbovirus infection in Ghana, which is considered a non-endemic country, by combining mosquito surveillance with virus isolation and detection. This study reports the presence of cryptic species of mosquitoes in Ghana, demonstrating the need to combine morphological identification and molecular techniques in mosquito surveillance. Furthermore, although no medically important viruses were detected, the importance of insect-specific viruses in understanding virus evolution and arbovirus transmission is discussed. This study reports the first mutualistic relationship between dengue virus and the double-stranded RNA Aedes aegypti totivirus. Finally, this study discusses the complexity of the virome of Aedes and Culex mosquitoes and its implication for arbovirus transmission.

7.
Gastric Cancer ; 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32065304

RESUMO

BACKGROUND: Few well-controlled studies have compared postoperative complications between Billroth I (B-I) and Roux-en-Y (R-Y). The aim of the present study was to compare the incidence of overall and severe postoperative complications by reconstruction method after distal gastrectomy. METHODS: We performed a multi-institutional dataset study of patients who underwent distal gastrectomy with B-I or R-Y reconstruction from 2010 to 2014. Using propensity scores to strictly balance the significant variables, we compared postoperative complications between the techniques. RESULTS: After matching, we enrolled 1014 patients (n = 507 in each group). The incidence of postoperative complications in the R-Y group was significantly higher vs the B-I group (29% vs 17%, P < 0.0001). The incidence of intra-abdominal abscess (4.3% vs 1.8%, P = 0.0177), bowel obstruction (2.6% vs 0.6%, P = 0.0203), and delayed gastric emptying (5.3% vs 1.0%, P < 0.0001) in the R-Y group was significantly higher vs the B-I group, respectively; we saw no significant difference in leakage (3.4% vs 4.1%, P = 0.5084). The incidence of grade ≥ III severe postoperative complications in the R-Y group was significantly higher vs the B-I group (13% vs 7.1%, P = 0.0013). Multivariable analysis showed that R-Y reconstruction was a strong independent risk factor for overall postoperative complications (odds ratio 1.58, P = 0.0044) and grade ≥ III severe postoperative complications (odds ratio 1.75, P = 0.0127). A forest plot revealed that R-Y reconstruction was associated with a greater risk of both overall and grade ≥ III severe postoperative complications in any subgroups. CONCLUSIONS: R-Y reconstruction was associated with increasing overall postoperative complications, as well as severe postoperative complications.

8.
Circ J ; 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32074552

RESUMO

BACKGROUND: Although schools are key places that conduct cardiopulmonary resuscitation (CPR) and public-access defibrillation (PAD) programs, out-of-hospital cardiac arrest (OHCA) in educational institutions is poorly understood. This study describes the characteristics and outcomes of such OHCAs.Methods and Results:Data for OHCAs of any cause occurring in educational institutions between 2013 and 2015 were extracted from the All-Japan Utstein Registry. Patient characteristics and outcomes were documented. Subjects were divided into 6 age groups (0-1, 2-5, 6-11, 12-14, 15-17, and ≥18 years). Among the 783 eligible OHCA patients, most received bystander CPR regardless of age, ranging from 73.9% in those aged ≥18 years to 90.0% in those aged 2-5 years. However, the proportion receiving PAD differed by age group, ranging from 2.9% in those aged 0-1 years to 66.7% in those aged 12-14 years. The proportion of patients with 1-month survival with favorable neurological outcome differed significantly by age group, being extremely low among patients aged 0-1 years (zero for OHCA of cardiac origin), but high among patients aged 6-11, 12-14, and 15-17 years (69.2%, 77.5%, and 70.0%, respectively) for OHCA of cardiac origin. CONCLUSIONS: The outcomes of OHCA occurring in educational institutions, where PAD is available, differed significantly by age.

9.
Ticks Tick Borne Dis ; 11(2): 101364, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31928929

RESUMO

Tick-borne viruses have emerged recently in many parts of the world, and the discoveries of novel tick-borne viruses have been accelerated by the development of high-throughput sequencing technology. In this study, a cost-efficient small benchtop next-generation sequencer, the Illumina MiniSeq, was used for the RNA virome analysis of questing ticks collected from Hokuriku District, Japan, and assessed for their potential utility in a tick-borne virus surveillance system. We detected two phleboviruses [Kabuto Mountain virus (KAMV) and Okutama tick virus (OKTV)], a coltivirus [Tarumizu tick virus (TarTV)], and a novel iflavirus [Hamaphysalis flava iflavirus (HfIFV)] from tick homogenates and/or cell culture supernatants after virus isolation processes. The number of sequence reads from KAMV and TarTV markedly increased when cell culture supernatants were used, indicating a successful isolation of these viruses. In contrast, OKTV and HfIFV were detected only in tick homogenates but not from cell culture supernatants, suggesting a failure to isolate these viruses. Furthermore, we performed genomic and phylogenetic analyzes of these detected viruses. OKTV and some phleboviruses discovered recently by NGS-based methods were probably deficient in the M genome segment, which are herein proposed as M segment-deficient phlebovirus (MdPV). A phylogenetic analysis of phleboviruses, including MdPV, suggested that Uukuniemi and Kaisodi group viruses and kabutoviruses evolved from an ancestral MdPV, which provides insights into the evolutionary dynamics of phleboviruses as emerging pathogens.

10.
Int Heart J ; 61(1): 46-53, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-31956145

RESUMO

We investigated the impact of bystander-initiated cardiopulmonary resuscitation (CPR), dispatcher assistance (DA), and location of arrest on survival and outcomes after out-of-hospital cardiac arrest (OHCA).From a nationwide population-based registry of OHCA patients in Japan, we enrolled adult patients with bystander-witnessed OHCA of medical origin between 2013 and 2015. The primary outcome measure was a neurologically favorable outcome, defined by cerebral performance category 1 or 2. Multivariable logistic regression analysis was used to assess the effects of bystander CPR and DA by location of arrest. A total of 104,621 cases were included (15,984 bystander CPR without DA [15.3%], 40,087 bystander CPR with DA [38.3%], and 48,550 no bystander CPR [46.4%]). In public locations, both the bystander-CPR-with-DA group (22.9% [1,068/4,665]; adjusted odds ratio (AOR), 1.62; 95% confidence interval (CI), 1.43-1.85) and the bystander-CPR-without-DA group (25.8% [918/3,557]; AOR, 1.43; 95% CI, 1.24-1.65) had neurologically favorable outcomes compared with the no-bystander-CPR group (9.9% [610/6,133]). In residential locations, the AORs were 1.44 (95% CI, 1.22-1.70) in the bystander-CPR-without-DA group and 1.60 (95% CI, 1.45-1.77) in the bystander-CPR-with-DA group. However, in nursing homes, bystander CPR was not associated with improved outcomes of OHCA, regardless of the implementation of DA.Bystander CPR with or without DA had better outcomes after OHCA in residential and public locations but not in nursing homes.


Assuntos
Reanimação Cardiopulmonar/métodos , Parada Cardíaca Extra-Hospitalar/terapia , Idoso , Idoso de 80 Anos ou mais , Serviços Médicos de Emergência , Feminino , Humanos , Japão , Modelos Logísticos , Masculino , Casas de Saúde , Análise de Sobrevida , Resultado do Tratamento
11.
Anticancer Res ; 40(1): 201-211, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31892568

RESUMO

BACKGROUND/AIM: This retrospective study focused on the correlation between molecular markers and prognostic outcomes of colon cancer patients depending on sidedness. MATERIALS AND METHODS: A total of 117 stage I-III colon cancer patients who underwent colectomy were enrolled. Novel methylation markers (KIF1A, PAX5 and VGF) were selected for epigenetic evaluation and p53 and ERCC1 protein expression was examined for the investigation of genetic alterations. RESULTS: High frequency of methylation was observed in 68.2% of right-sided and 39.7% of left-sided colon cancer cases (p=0.004). Abnormal p53 was identified in 52.3% of right-sided and 75.3% of left-sided cases (p=0.015). In right-sided cases, highly methylated genes demonstrated significantly favorable disease-free survival (p=0.049). Regarding left-sided cases, advanced T stage (p=0.028) and abnormal p53 (p=0.028) were revealed to be significant predictive factors of the disease-free survival outcome. CONCLUSION: Molecular alterations, as significant prognostic factors, might differ depending on the sidedness of colon cancers.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Idoso , Metilação de DNA/genética , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Análise Multivariada , Proteínas de Neoplasias/metabolismo , Curva ROC , Análise de Sobrevida
12.
Biol Pharm Bull ; 43(1): 49-52, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31902931

RESUMO

Few therapeutic options exist for gemcitabine-resistant pancreatic cancer. In this study, we investigated the anti-cancer effects of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors and bisphosphonates in pancreatic cancer cell lines (SUIT-2 and MIA PaCa-2) which show poor responses to gemcitabine, established through long-term culture in nutrient-deprived or gemcitabine-containing media. Under the nutrient-deprived condition, IC50s for statins and bisphosphonates decreased and those for gemcitabine increased compared with those under normal conditions. In cells cultured long-term with gemcitabine, although IC50s for gemcitabine increased, those for statins and bisphosphonates either slightly increased or remained unchanged. Thus, these drugs may be effective against pancreatic cancer cells which show poor responses to gemcitabine.

13.
Histopathology ; 76(4): 603-612, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31643099

RESUMO

AIMS: Lymph node metastasis (LNM) has not been found in more than 85% of patients with early invasive colorectal adenocarcinoma (T1-CRAC) who undergo surgery after therapeutic endoscopy due to the risk for LNM. Better histological risk assessment for LNM of endoscopically resected T1-CRAC is important to avoid unnecessary additional surgery. METHODS AND RESULTS: We evaluated cancer gland rupture (CGR), i.e. cancer glands with a discontinuous epithelial lining, at the invasive front, as a potential risk factor for LNM by histological examination of differentiated T1-CRAC from 217 patients who underwent surgery with or without therapeutic endoscopy. CGR was represented by C-shaped neoplastic glands with a variable inflammatory or stromal reaction, and was occasionally accompanied by mucus lake or abscess formation. CGR was observed in 168 (77%) cases, including all 20 cases with LNM, and the odds ratio of LNM was higher for CGR than for deep invasion (depth of submucosal invasion ≥1000 µm). All cases with LNM were found among 148 cases with deep invasion and positive CGR, whereas no LNM was detected in 29 cases with deep invasion and negative CGR, regardless of vascular invasion or tumour budding. In the 148 cases, LNM was detected in 18 (19%) of 93 cases with positive vascular invasion or high-grade tumour budding, and in two (4%) of 55 cases without either. CONCLUSIONS: Our findings suggest that CGR is an easily applied and objective histological finding for predicting LNM that could be useful for assessing the risk for LNM of endoscopically resected T1-CRAC with deep invasion.

14.
Ann Thorac Surg ; 109(3): 835-841, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31525348

RESUMO

BACKGROUND: Down syndrome (DS) is considered a risk factor for mortality associated with the Fontan operation. The objective was to show the contemporary short-term outcome of the Fontan operation for a functionally univentricular heart in patients with DS and non-DS, along with an analysis of significant predictors for in-hospital mortality. METHODS: This was a retrospective study using The Society of Thoracic Surgeons Congenital Database to assess in-hospital mortality and its predictors in patients with DS and non-DS undergoing the Fontan operation over 16 years (2001-2016). The primary outcome was in-hospital mortality. Statistical analysis was performed using univariable and multivariable logistic regression models. RESULTS: Our study cohort consisted of 12,074 patients (81 DS and 11,993 non-DS). The overall in-hospital mortality rate significantly improved in the recent era (2009-2016): 2.4% to 1.3%, P < .001. The DS group had a higher in-hospital mortality rate (12.3% vs 1.6%, P < .001) with an odds ratio of 8.6 (95% confidence interval, 4.4-17.0). The DS group had a higher 30-day mortality rate, a longer median postoperative length of stay, and a higher incidence of postoperative complications. The multivariable model showed that DS was the strongest predictor of in-hospital mortality, with an odds ratio of 11.6 (95% confidence interval, 5.1-26.4), adjusted for other significant variables including era effect, weight, and primary cardiac diagnosis. CONCLUSIONS: The in-hospital mortality for the Fontan operation significantly improved in the contemporary era. DS was a significant risk factor for in-hospital morbidity and mortality associated with the Fontan operation.

15.
Int J Clin Oncol ; 25(1): 118-125, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31542847

RESUMO

OBJECTIVE: This multicenter, single-arm phase II study (UMIN000008429) aimed to evaluate the efficacy and safety of capecitabine plus oxaliplatin (CapOX) as postoperative adjuvant chemotherapy for patients with locally advanced rectal cancer. METHODS: Patients with resectable clinical Stage II or III rectal cancer were enrolled to receive eight cycles of CapOX therapy (130 mg/m2 oxaliplatin on day 1 and 2000 mg/m2 oral capecitabine on days 1-14, every 3 weeks) after curative surgical resection. The primary endpoint was 3-year relapse-free survival (RFS) rate, and secondary endpoints were 3-year overall survival (OS) rate, treatment compliance, and safety. RESULTS: A total of 40 patients (Stage II, 21; Stage III, 19) were enrolled between September 2012 and November 2015 from seven institutions. Thirty-nine patients (97%) received R0 resection, and 32 patients (84%) received postoperative CapOX therapy. The completion rate of all eight cycles of CapOX therapy was 66%. Relative dose intensities were 87% for oxaliplatin and 84% for capecitabine. At a median follow-up period of 46 months, disease recurrence was observed in nine patients, including three with local recurrence. Three-year RFS and OS rates were 75% (95% CI 57-86%) and 96% (95% CI 80-99%), respectively. Frequencies of Grade ≥ 3 hematological and non-hematologic adverse events were 19% and 38%, respectively. CONCLUSION: CapOX therapy is feasible as adjuvant chemotherapy for locally advanced rectal cancer.

16.
Gastric Cancer ; 23(2): 203-211, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31377880

RESUMO

BACKGROUND: Development of high-performance serum biomarkers will likely improve treatment outcomes of patients with gastric cancer (GC). We previously identified the candidate serum markers, anosmin 1 (ANOS1), dihydropyrimidinase-like 3 (DPYSL3), and melanoma-associated antigen D2 (MAGE-D2) and evaluated their clinical significance through a single-center retrospective analysis. Here we conducted a prospective multicenter observational study aimed at validating the diagnostic performance of these potential markers. METHODS: We analyzed serum levels before and after surgery of the three potential biomarkers in patients with GC and healthy volunteers. Quantification of serum and GC tissue levels was performed using an ELISA. RESULTS: Area under the curve (AUC) values that discriminated patients with GC from healthy controls were - 0.7058, 0.6188, and 0.5031 for ANOS1, DPYSL3, and MAGED2, respectively. The sensitivity and specificity of the ANOS1 assay were 0.36 and 0.85, respectively. The AUC value of ANOS1 that discriminated patients with stage I GC from healthy controls was 0.7131. Serum ANOS1 levels were significantly elevated in patients with stage I GC compared with those of healthy controls (median 1179 ng/ml and 461 ng/ml, respectively, P < 0.0001) and decreased after resection of primary GC lesions (P < 0.0001). The combination of serum ANOS1 and DPYSL3 levels increased the AUC value that discriminated patients with GC from healthy controls. Serum levels of ANOS1 did not significantly correlate with those of carcinoembryonic antigen, carbohydrate antigen 19-9, or other markers of inflammation. CONCLUSIONS: Serum levels of ANOS1 may serve as a useful diagnostic tool for managing GC.

17.
J Nat Med ; 74(1): 83-89, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31346973

RESUMO

We explored new cytotoxic C19-diterpenoid alkaloid, lipojesaconitine (1), from rhizoma of Aconitum japonicum THUNB. subsp. subcuneatum (NAKAI) KADOTA. Two additional non-cytotoxic new C19-diterpenoid alkaloids, 10-hydroxychasmanine (2) and 3-hydroxykaracoline (3), together with eight known C19- and C20-diterpenoid alkaloids (4-11) were also isolated. Their structures were elucidated by extensive spectroscopic methods including NMR (1D and 2D), IR, and MS (HRMS). Six known diterpenoid alkaloids, foresticine (5), neolinine (6), aconicarchamine A (7), 9-hydroxynominine (8), kobusine (9), and torokonine (10), were isolated for the first time from A. japonicum subsp. subcuneatum. Alkaloid 1 showed cytotoxicity with IC50 values ranging from 6.0 to 7.3 µM against four human tumor cell lines, except a multidrug-resistant subline, suggesting that 1 was likely exported by P-glycoprotein.

18.
Ann Surg Oncol ; 27(1): 268-275, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31493125

RESUMO

BACKGROUND: Laparoscopic gastrectomy (LG) is a standard approach for patients with clinical stage I gastric cancer in East Asia; however, following surgery, these patients may be pathologically diagnosed with stage II or III cancer. The prognosis of patients with gastric cancer migration from clinical stage I to pathological stage II or III after LG has not been completely clarified. METHODS: To compare the prognosis following LG and open gastrectomy (OG) in patients with pathological stage II or III gastric cancer who were preoperatively diagnosed with stage I cancer, we conducted a retrospective analysis using a multicenter dataset comprising details of 3480 patients who underwent gastrectomy between 2010 and 2014 at nine participating institutions. We used propensity score matching to reduce selection bias. RESULTS: After propensity score matching, 146 patients were finally selected. There were no significant differences in the number of dissected lymph nodes. Morbidity rates, length of postoperative hospital stay, and time between surgery and initiation of adjuvant chemotherapy were comparable between the two groups. Moreover, there were no significant differences in the overall, disease-specific, and relapse-free survival rates between the LG and OG groups. The LG group tended to have more patients with hematogenous recurrence, whereas the OG group tended to have more patients with peritoneal recurrence. CONCLUSIONS: Our multicenter dataset analysis indicated that the prognosis of patients with gastric cancer migration from clinical stage I to pathological stage II or III was independent of the surgical approach.

19.
Oncology ; 98(1): 48-52, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31487733

RESUMO

INTRODUCTION: Intraperitoneal (IP) chemotherapy is a promising treatment option for gastric cancer (GC) with peritoneal metastasis (PM). Recently, superiority of IP administration of paclitaxel (PTX) combined with S-1 and intravenous PTX over conventional systemic chemotherapy was suggested in a phase III study, although the difference in overall survival did not reach statistical significance in the primary analysis. Thus, attempts to combine IP PTX with other systemic therapies with higher efficacy are warranted. We designed a new regimen combining IP PTX with S-1 plus cisplatin (SP), which is regarded as the standard first-line treatment for metastatic GC in Japan, and subsequently carried out a dose-escalation study. METHODS: The combination was a 5-weekly regimen. IP PTX was to be administered on days 1, 8, and 22 with an initial dose of 15 mg/m2 at level 1 and 20 mg/m2 at level 2. S-1 was to be administered orally at a fixed dose of 80 mg/m2 b.i.d. for 21 days followed by a -14-day rest. Cisplatin was to be administered intravenously at a dose of 60 mg/m2 on day 8. Dose-limiting toxicities (DLTs) were defined as grade 4 leukopenia, grade 3 (G3) febrile neutropenia, G3 thrombocytopenia, and G3 nonhematological toxicity. RESULTS: A total of 9 patients with macroscopic PM were enrolled. No DLTs were observed among the 3 patients at level 1 and 6 patients at level 2. No adverse events or technical problems associated with the IP administration were observed. Consequently, the maximum-tolerated dose was not reached, and the dose for further clinical trials of IP PTX was determined as 20 mg/m2. As for efficacy, peritoneal lavage cytology turned negative after the first course in 4 of 7 patients who had positive cytology before treatment. CONCLUSION: The present study determined the dose for further clinical trials of IP PTX to be 20 mg/m2, when combined with the 5-weekly SP regimen.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Cisplatino/administração & dosagem , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Ácido Oxônico/administração & dosagem , Paclitaxel/administração & dosagem , Neoplasias Peritoneais/secundário , Neoplasias Gástricas/patologia , Tegafur/administração & dosagem , Resultado do Tratamento
20.
World J Surg ; 44(1): 194-201, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31552460

RESUMO

BACKGROUND: Little is known about the changes in prognostic factors after adjuvant S-1 monotherapy has become widespread as a standard of care for patients with gastric cancer (GC) in East Asia. The present study compared prognostic factors of patients with stage II/III GC treated with or without S-1 adjuvant to formulate appropriate risk stratification strategies. METHODS: We designed a large multicenter dataset and retrospectively analyzed 847 patients with GC stage II or III, who underwent curative gastrectomy between 2010 and 2014. Clinicopathological features and prognostic factors were compared between the two patient groups: surgery-alone (n = 266) and S-1 adjuvant (n = 581). RESULTS: There were no significant differences in pathological tumor depths, nodal status, and disease stages between groups. Recurrence-free survival was significantly longer in the S-1 adjuvant group. For the surgery-alone group, independent prognostic factors were (in order of hazard ratio): (1) invasive growth, (2) high preoperative carcinoembryonic antigen levels, (3) total gastrectomy. For the S-1 adjuvant group, macroscopic tumor size (≥50 mm) was identified as another independent prognostic factor next only to pN2/3. There was overlap between the survival curves of patients with tumor size ≥50 mm in both groups. After receiving adjuvant S-1 monotherapy, ≥50 mm patients had significantly higher prevalence of peritoneal and lymph node metastasis as initial recurrences compared with <50 mm patients. CONCLUSIONS: Adjuvant S-1 monotherapy may alter listing of adverse prognostic factors of stage II and III patients. Macroscopic tumor size ≥50 mm may serve as an important determinant for risk stratification to identify patients who require more intensive treatment.

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