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1.
PLoS One ; 16(9): e0256575, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34550993

RESUMO

With increasing concern over online misinformation in perspective, this study experimentally examined the cognitive as well as the affective consequences of online search. Results of the two experiments using widely shared, prejudiced misinformation about an ethnic minority in Japan indicated that (a) online search reduces on average the likelihood of believing the misinformation, (b) the magnitude of the effect is larger among those who are predisposed to believe the misinformation, (c) cognitive correction is observed whether searchers are motivated to achieve a directional goal or an accuracy goal, and (d) online search deteriorates affective feeling toward the target groups of the misinformation. Theoretical implications are discussed in relation to the robustness of confirmation bias in online search and the "belief echo" in which exposure to negative misinformation continues to shape attitudes even after the misinformation has been effectively discredited.


Assuntos
Cognição/fisiologia , Comunicação , Internet/normas , Motivação/fisiologia , Adulto , Atitude , Grupos Étnicos , Feminino , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Grupos Minoritários , Mídias Sociais , Adulto Jovem
2.
Front Oncol ; 11: 695251, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34395260

RESUMO

Background: Prostate cancer has become increasingly common worldwide. Although Grade group (GG) is widely accepted as an indicator of prostate cancer grade, there are malignancies that cannot be defined by GG alone. Moreover, the relationship between GG and other parameters remains unclear. Herein, we aimed to explore the biological characteristics of prostate cancer. Methods: This study included 299 radical prostatectomy cases. The Chi-square test and analysis of variance were used to analyze the association of GG with binary and continuous variables. We then conducted morphological analyses. Multivariate analyses were performed to extract the data on risk factors for biochemical recurrence (BCR) and lymph node metastasis. Results: The lymphatic, venous, perineural, and seminal vesicle invasion rates were 37/299 (12.4%), 25/299 (8.4%), 280/299 (93.6%), and 23/299 (7.7%), respectively. The extraprostatic extension (EPE), positive surgical margin, tertiary Gleason pattern 5, intraductal carcinoma of the prostate gland, and lymph node metastasis rates were 89/299 (29.8%), 106/299 (35.5%), 33/260 (12.7%), 56/299 (18.7%), and 23/299 (7.7%), respectively. As GG increased, various parameters became easier to visualize; however, there were differences between the parameters. Postoperative BCR was observed in 31/242 (12.8%) cases without preoperative hormone therapy; GG2, GG3, GG4, and GG5 accounted for 4, 7, 7, and 13 cases, respectively. Multivariate analyses revealed that GG and tumor diameter were significant risk factors for early BCR, whereas lymphatic invasion, EPE, and seminal vesicle invasion were significant risk factors for lymph node metastasis. For BCR, the odds ratios (ORs) for GG and tumor diameter were 2.253 (95% confidence interval (CI]): 1.297-3.912; P=0.004) and 1.074 (95% CI: 1.011-1.142; P=0.022), respectively. For lymph node metastasis, ORs for the presence of lymphatic invasion, EPE, and seminal vesicle invasion were 7.425 (95% CI: 1.688-22.583; P=0.004), 4.391 (95% CI: 1.037-18.589; P=0.044), and 5.755 (95% CI: 1.308-25.316; P=0.021), respectively. Conclusions: We summarized various parameters correlating with each GG. Through multivariate analyses, we established the independent risk factors for early BCR and lymph node metastasis. In addition to GG, other important indices of malignancy were determined and weighted to provide a basis for future investigations.

3.
Gastric Cancer ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34427838

RESUMO

BACKGROUND: There is no large real-world data regarding efficacy and safety of immunotherapy in gastric cancer (GC). Although some tumors can grow rapidly after immunotherapy, the patient proportions and survival outcomes are unclear in GC. METHODS: A multicenter, prospective observational study was performed to evaluate clinical outcomes including survival time, safety, and tumor behavior of nivolumab treatment for patients with advanced GC. Primary endpoint was overall survival (OS), and secondary endpoints included response rate (RR), disease control rate (DCR), progression-free survival (PFS), tumor growth rate (TGR) at first evaluation, and safety. RESULTS: Of 501 enrolled patients, 487 were evaluable (median age 70 years, 71% male, performance status 0/1/2 [42%/44%/14%], 21% HER2-pos, 42% patients with ascites). Median OS was 5.82 months (95% CI 5.29-7.00) with a 1-year survival rate of 30% and median PFS of 1.84 months (95% CI 1.71-1.97). The DCR was 39.4% and the RR was 14.2% (95% CI 10.3-18.8) in 282 patients with measurable lesions. In 219 patients evaluable for TGR, 20.5% were identified as hyperprogressive disease (HPD). OS from the first evaluation of patients with HPD was shorter compared with non-HPD (HR 1.77, 95% CI 1.25-2.51, P = 0.001), but it was not worse than that of patients with progression and non-HPD (HR 1.05, 95% CI 0.72-1.53, P = 0.8). A multivariate analysis revealed the presence of peritoneal metastasis was a prognostic factor for OS and PFS. CONCLUSIONS: Our real-world data demonstrated the comparable survival time to a previous clinical trial and revealed the frequency and prognosis of patients with HPD in advanced GC treated with nivolumab.

4.
Am J Case Rep ; 22: e932924, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34358221

RESUMO

BACKGROUND The efficacy and safety of re-challenge with immune checkpoint inhibitors after immune-related adverse events have not been established. We report a case of successful re-administration of nivolumab in metastatic renal cell carcinoma after discontinuation due to immune-related adverse events. CASE REPORT Laparoscopic nephrectomy was performed on a 52-year-old man diagnosed with renal cell carcinoma pT1bN0M0. After surgery, left adrenal and lung metastases appeared. Nivolumab was administered as a sixth-line therapy, and he achieved a partial response, but interstitial pneumonia occurred. He was diagnosed with grade 2 immune-related adverse events, and nivolumab treatment was discontinued. Interstitial pneumonia was well controlled by steroids. He maintained a partial response for a long time, and the lung metastases disappeared 7 months after discontinuation. However, bilateral lung metastases reappeared 10 months after the discontinuation. We decided to re-administer nivolumab, while carefully monitoring the patient and fully explaining the risk of recurrence of immune-related adverse events. After 5 cycles of re-administration, computed tomography revealed a reduction in metastases without re-activation of interstitial pneumonia. He experienced a grade 1 fever the day after re-administration, but continued nivolumab therapy without other adverse events. After 7 cycles of re-administration, the lung metastases increased, and nivolumab treatment was terminated. Two months later, a grade 2 interstitial pneumonia recurred, but improved rapidly with oral steroids. CONCLUSIONS For patients who have discontinued immune checkpoint inhibitors due to immune-related adverse events, re-challenge of immune checkpoint inhibitors may be an option after explaining the risk of relapse of immune-related adverse events.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Doenças Pulmonares Intersticiais , Carcinoma de Células Renais/tratamento farmacológico , Humanos , Neoplasias Renais/tratamento farmacológico , Doenças Pulmonares Intersticiais/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Nivolumabe/efeitos adversos
5.
Nat Commun ; 12(1): 4956, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34400643

RESUMO

In recent years, considerable research and development efforts are devoted to improving the performance of polymer electrolyte fuel cells. However, the power density and catalytic activities of these energy conversion devices are still far from being satisfactory for large-scale operation. Here we report performance enhancement via incorporation, in the cathode catalyst layers, of a ring-structured backbone matrix into ionomers. Electrochemical characterizations of single cells and microelectrodes reveal that high power density is obtained using an ionomer with high oxygen solubility. The high solubility allows oxygen to permeate the ionomer/catalyst interface and react with protons and electrons on the catalyst surfaces. Furthermore, characterizations of single cells and single-crystal surfaces reveal that the oxygen reduction reaction activity is enhanced owing to the mitigation of catalyst poisoning by sulfonate anion groups. Molecular dynamics simulations indicate that both the high permeation and poisoning mitigation are due to the suppression of densely layered folding of polymer backbones near the catalyst surfaces by the incorporated ring-structured matrix. These experimental and theoretical observations demonstrate that ionomer's tailored molecular design promotes local oxygen transport and catalytic reactions.

6.
J Gastrointest Surg ; 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34379296

RESUMO

BACKGROUND: Transmembrane serine protease 4 (TMPRSS4) belongs to the family of type II transmembrane serine proteases that are known to be upregulated in many malignant tumors. However, there is a paucity of studies documenting the clinical impact and biological effects of TMPRSS4 on gastric cancer (GC) patients who underwent surgery. METHODS: Tissues samples were obtained from 105 patients with GC who underwent gastrectomy followed by adjuvant chemotherapy, excluding those at stage I. The expression of TMPRSS4 was examined through immunohistochemical analysis. The association between TMPRSS4 expression and clinico-pathological features as well as prognosis was assessed. Moreover, the effects of TMPRSS4 expression on cell migration and sensitivity to 5-FU were investigated. RESULTS: The expression rate of TMPRSS4 was 56.3% (59/105) in GC cases. The expression of TMPRSS4 was positively correlated with the depth of tumor (T) and venous (V) invasion. The 5-year overall survival (OS) and recurrence-free survival (RFS) rates of the TMPRSS4-positive group was significantly lower than that of the TMPRSS4-negative group (p=0.0001 and p=0.005, respectively). Especially, there was significant differences in OS and RFS of patients with stage III cancer between the two groups (p=0.0064 and 0.012, respectively). Multivariate analysis demonstrated that TMPRSS4 expression and the stage of cancer were crucial prognostic factors for RFS. TMPRSS4-silenced GC cells exhibited increased sensitivity to 5-FU when compared with the non-specific control siRNA-transfected cells. CONCLUSION: TMPRSS4 can be considered as a potential prognostic biomarker, especially for stage III, and a promising therapeutic target for GC.

7.
Int J Surg Case Rep ; 84: 106161, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34237686

RESUMO

INTRODUCTION AND IMPORTANCE: Nivolumab, which is a fully human IgG4 PD-1 immune checkpoint inhibitor antibody, has been recommended as a third-line treatment based on the results of the ATTRACTION-2 study involving patients with unresectable advanced gastric cancer. CASE PRESENTATION: A 69 year-old woman was referred to our department with a diagnosis of gastric cancer based on an upper gastrointestinal endoscopy during a medical examination. The endoscopy, along with various tests, helped establish a diagnosis of unresectable advanced gastric cancer (cT4aN3aM1P1c, cStage IV) with peritoneal dissemination. The first and second-line chemotherapy administered was S-1 plus oxaliplatin followed by ramucirumab and nab-paclitaxel, respectively. In this case, the disease was evaluated as progressive disease due to increased peritoneal dissemination. Nivolumab was administered as the third-line treatment. The patient developed interstitial pneumonia after nine courses of nivolumab, for which chemotherapy was discontinued and prednisolone treatment was initiated. The patient had a complete response to treatment endoscopically, 9 months after the last administration of nivolumab. After that, there was no recurrence of the cancer, despite there being no treatment for 5 months. CLINICAL DISCUSSION: It was suggested that the therapeutic effect of nivolumab could be maintained for a long period after discontinuation of its administration. In addition, a correlation has been reported between the treatment efficacy and immune-related adverse events associated with nivolumab. CONCLUSIONS: The synergistic effect of the sustained effect of nivolumab and later-line treatment may contribute to the prolongation of survival after discontinuation of nivolumab in patients who are refractory or intolerant to treatment.

8.
Arthritis Res Ther ; 23(1): 197, 2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34301311

RESUMO

OBJECTIVE: To compare the efficacy and safety of tofacitinib and baricitinib in patients with RA in a real-world setting. METHODS: A total of 242 patients with RA who were treated with tofacitinib (n = 161) or baricitinib (n = 81) were enrolled. We evaluated efficacy and safety between tofacitinib and baricitinib using multivariable analyses to avoid confounding. Their clinical disease activity and AEs were evaluated for 24 weeks. RESULTS: The mean (SD) DAS28-ESR change from baseline to 24 weeks was 1.57 (1.55) (tofacitinib) and 1.46 (1.36) (baricitinib). There was no significant difference in the clinical response between the two groups (adjusted mean difference, 0.04; 95% CI, -0.35 to 0.28). The efficacy was not significantly changed in the patients without concomitant MTX use in both groups, but the concomitant MTX use showed better clinical efficacy in the cases of baricitinib treatment. In both groups, the most common AE was herpes zoster infection, and the AE rates were similar between the two groups. However, the predictive factors contributing to clinical response as revealed by a multivariable logistic analysis differed. The concomitant oral steroid use was independently associated with the achievement of DAS-low disease activity in the tofacitinib group, whereas in the baricitinib group, the number of biological and/or targeted synthetic DMARDs previously used was associated. CONCLUSIONS: Our findings indicate that tofacitinib and baricitinib had comparable continuing efficacies and safety profiles. However, there is a possibility that the influence of clinical characteristics on the treatment response differs. The comparison provides useful information to the optimal use of JAK inhibitors in real-world settings.


Assuntos
Antirreumáticos , Artrite Reumatoide , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Azetidinas , Humanos , Piperidinas/efeitos adversos , Purinas , Pirazóis , Pirimidinas/efeitos adversos , Pirróis/efeitos adversos , Sulfonamidas , Resultado do Tratamento
9.
Neurourol Urodyn ; 40(6): 1460-1469, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34015154

RESUMO

AIMS: Spinal cord injury (SCI) above the sacral level causes bladder dysfunction and remodeling with fibrosis. This study examined the antifibrotic effects using nintedanib, an inhibitor of vascular endothelial growth factor, fibroblast growth factor, and platelet-derived growth factor receptors, on detrusor overactivity (DO) and bladder fibrosis, as well as the modulation mechanisms of C-fiber afferent pathways. METHODS: Thirty female C57BL/6 mice were divided into group A (spinal intact), group B (SCI with vehicle), and group C (SCI with nintedanib). At 2 weeks after SCI, vehicle or 50 mg/kg nintedanib was administered subcutaneously for 2 weeks. Then, cystometry was conducted, followed by RT-PCR measurements of fibrosis-related molecules, muscarinic, ß-adrenergic, TRP and purinergic receptors in the bladder or L6-S1 dorsal root ganglia (DRG). Trichrome stain and Western blot analysis of transforming growth factor-beta and fibronectin were performed in the bladder. TRPV1 expression in L6 DRG was measured by immunohistochemistry. RESULTS: In cystometry, intercontraction intervals, nonvoiding contractions, voided volume, and voiding efficiency were significantly improved in group C versus group B. RT-PCR, Western blotting, and trichrome staining revealed the fibrotic changes in the bladder of group B, which was improved in group C. Increased messenger RNA levels of TRPV1, TRPA1, P2X2 , and P2X3 in DRG of group B were significantly decreased in group C. TRPV1 immunoreactivity in DRG was increased in group B, but decreased in group C. CONCLUSIONS: Nintedanib improves storage and voiding dysfunctions and bladder fibrosis in SCI mice. Also, nintedanib-induced improvement of DO is associated with reduced expression of C-fiber afferent markers, suggesting the modulation of bladder C-fiber afferent activity.

10.
J Pharmacol Sci ; 146(1): 65-69, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33858657

RESUMO

The blood-brain barrier (BBB) is mainly formed by brain capillary endothelial cells (BCECs) and is exposed to hypoxic environments under pathological conditions. The effects of hypoxia on the expression and activity of Ca2+-activated Cl- (ClCa) channels, TMEM16A, were examined in bovine brain endothelial t-BBEC117 cells and mouse BCECs. The expression of TMEM16A was upregulated by hypoxia. Whole-cell ClCa currents increased under hypoxia. Hypoxia also increased cell proliferation and trans-endothelial permeability, which were attenuated by ClCa channel blockers or TMEM16A siRNA. These findings are useful for elucidating the pathological role of TMEM16A ClCa channels in the BBB during cerebral ischemia.


Assuntos
Anoctamina-1/genética , Anoctamina-1/metabolismo , Barreira Hematoencefálica/citologia , Barreira Hematoencefálica/patologia , Encéfalo/citologia , Proliferação de Células , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Expressão Gênica/genética , Hipóxia-Isquemia Encefálica/genética , Hipóxia-Isquemia Encefálica/patologia , Regulação para Cima/genética , Animais , Bovinos , Linhagem Celular , Camundongos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo
12.
Int J Surg Case Rep ; 81: 105727, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33714895

RESUMO

INTRODUCTION: Neoadjuvant imatinib for large GISTs may prevent tumor rupture and the need for extended surgery by reducing tumor size. In this study, we present a case of large gastric GIST with diaphragm invasion, due to the patient receiving laparoscopic resection following preoperative imatinib treatment. PRESENTATION OF CASE: A 72-year-old woman was hospitalized with left hypochondriac pain for a month. Examinations revealed a large heterogeneous gastric mass measuring 80 mm in size, arising from the greater curvature of the corpus. The mass invaded the left thoracic diaphragm. Treatment with imatinib at an initial dosage of 400 mg/day was initiated. After a further two months of follow-up, the lesion had sustained reduction to 50 mm in size, however, the invasion to the diaphragm remained. The patient eventually underwent laparoscopic partial gastrectomy and partial resection of the diaphragm with curative intent. Adjuvant chemotherapy was initiated at one month after the surgery, however, was discontinued due to nausea. After one-year follow-up, no recurrence was noted. DISCUSSION: Neoadjuvant imatinib may shrink tumor size remarkably and prevent tumor rupture during surgery, and thus lead to increased rates of complete resection. To date, several publications have directly compared the oncologic results between laparoscopic and open resection for GISTs. In the present case, the tumor was movable, and moderately fixed on diaphragm. It was favorable condition for laparoscopic surgery. CONCLUSIONS: This is the first report of a large gastric GIST invading the diaphragm that was successfully treated by laparoscopic resection after tumor reduction by neoadjuvant imatinib.

13.
Gen Thorac Cardiovasc Surg ; 69(5): 890-893, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33400203

RESUMO

We present a case of the broncho-pleural fistula with a collapsed lung that was developed 2 weeks after right lower lobectomy. The patient urgently underwent open-window thoracostomy. However, the residual lung remained collapsed. To expand the lung and close the broncho-pleural fistula, negative pressure wound therapy was initiated 20 days after the procedure. The lung expanded within a few days, and the residual thoracic cavity gradually contracted. Subsequently, 2.5 months later, the remaining thoracic cavity was successfully closed using omentoplasty. No recurrence of the broncho-pleural fistula was observed for 1 year. If the lung could be inflated to reduce dead space in the thoracic cavity, broncho-pleural fistula with collapsed lung may be treated with bronchial stump coverage and negative pressure wound therapy.


Assuntos
Fístula Brônquica , Empiema Pleural , Tratamento de Ferimentos com Pressão Negativa , Doenças Pleurais , Fístula Brônquica/diagnóstico por imagem , Fístula Brônquica/etiologia , Fístula Brônquica/cirurgia , Empiema Pleural/cirurgia , Humanos , Pulmão , Doenças Pleurais/diagnóstico , Doenças Pleurais/etiologia , Doenças Pleurais/cirurgia , Pneumonectomia
14.
Mod Rheumatol ; 31(5): 972-978, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33161771

RESUMO

OBJECTIVES: Our previous study showed that the effectiveness of tumor necrosis factor (TNF) inhibitors was attenuated in anti-human T-cell leukemia virus type 1 (HTLV-1) antibody-positive patients with rheumatoid arthritis (RA). We aimed to evaluate the effectiveness and safety of non-TNF inhibitors in anti-HTLV-1 antibody-positive patients with RA. METHODS: We reviewed patients with RA who received abatacept or tocilizumab as the first biologic agent. We used the data of patients treated with TNF inhibitors from our previous study to compare the effectiveness between the anti-HTLV-1 antibody-positive patients treated with TNF inhibitors and non-TNF inhibitors using the inverse probability of treatment weights (IPTW) method. RESULTS: A total of 359 patients were divided into anti-HTLV-1 antibody-negative and -positive patients of 332 and 27, respectively. No statistically significant difference was observed in the change in the clinical disease activity index between the anti-HTLV-1 antibody-positive and -negative patients. The results using the IPTW method showed a significant association between the non-TNF inhibitors treatment and a better response. None of the patients developed adult T-cell leukemia/lymphoma or HTLV-1-associated myelopathy/tropical spastic paraparesis during the 24 weeks. CONCLUSION: Our results indicate that non-TNF inhibitors treatment is safety, and the effectiveness is not attenuated also in anti-HTLV-1 antibody-positive patients.


Assuntos
Artrite Reumatoide , Vírus Linfotrópico T Tipo 1 Humano , Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Humanos , Leucemia-Linfoma de Células T do Adulto , Paraparesia Espástica Tropical/tratamento farmacológico , Inibidores do Fator de Necrose Tumoral
15.
J Orthop Sci ; 26(4): 704-708, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32826137

RESUMO

BACKGROUND: Discrepancies exist between the magnitude of musculoskeletal problems and the competency of physicians practicing musculoskeletal medicine, which likely stems from medical school-level educational deficiencies. Therefore, inadequate orthopedic surgery education during medical school may affect the number of students aspiring to practice orthopedic surgery. However, the motivating factors underlying medical students' selection of a career specialty are largely unknown. This study aims to use a survey to examine the motivations of medical students who consider orthopedic surgery as a potential career specialty. METHODS: A questionnaire survey was administered to medical students in our medical faculty. The results were stratified on the basis of gender, year, and experience as a patient; results were then compared between students who wished to practice orthopedic surgery and those who did not consider it a potential specialty. RESULTS: Of the 499 students who responded to the questionnaire, 47% considered orthopedic surgery as their career specialty. Being male and having experienced orthopedic surgery as a patient were significant factors influencing the aspiration to practice orthopedic surgery (p < 0.001). In addition, the motivation for choosing orthopedic surgery was academic interest for 55% of students. In the first and fifth years, more than half of the students preferred an orthopedic surgery specialty. The percentage of fifth-year students who were candidates for orthopedic surgery as their career specialty significantly exceeded that of students in other years (p = 0.03). However, the percentage of students considering orthopedic surgery decreased in the sixth year. CONCLUSION: Our findings suggest that orthopedic surgeons should provide a clearer, more informative job description to attract female medical students' attention and change their negative perception of orthopedic surgery. Furthermore, including education that incorporates experiences closer to clinical practice at the medical-school level is important for increasing the number of candidates for orthopedics.


Assuntos
Procedimentos Ortopédicos , Ortopedia , Escolha da Profissão , Estudos Transversais , Docentes de Medicina , Feminino , Humanos , Masculino
16.
Acta Histochem Cytochem ; 53(5): 113-119, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33177783

RESUMO

Gastric cancer (GC) is the third most common cause of cancer-related mortality. The diagnosis and treatment of early GC is a crucial strategy for prognostic improvement of GC. Annexin A10 (ANXA10), a calcium-/phospholipid-binding protein, is a member of the annexin family. The significance of ANXA10 expression in early GC remains unclear. This is the first report to investigate ANXA10 expression in early GC. We performed immunohistochemistry to evaluate ANXA10 expression in early GC, and the correlation between ANXA10 and clinicopathological factors. The loss of ANXA10 expression was detected in 63 (61.2%) of 103 early GC cases and significantly correlated with poor overall survival in patients. Sex, pT stage, pN stage, histology, and ANXA10 expression were associated with poor survival. Sex, histology, and ANXA10 expression were determined as independent predictors of survival in early GC patients. ANXA10 immunostaining could be a new decision-making biomarker in GC.

17.
Life Sci ; 258: 118179, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32758626

RESUMO

OBJECTIVE: To evaluate whether approved gastroprokinetic agent, acotiamide exerts a direct excitatory effect on bladder to help explain the reported meaningful reduction of post-void residual urine volume (PVR) in detrusor underactivity (DU) patients after thrice daily oral intake of acotiamide 100 mg for 2 weeks. METHODS: Effect of acotiamide [1-16 µM] was assessed on nerve-mediated contractions evoked by electrical field stimulation (EFS) for 5 s with 5 ms pulse trains of 10 V in longitudinal, mucosa intact rat and human bladder strips to construct frequency response curve (1-32 Hz) and repeat 10 Hz stimulation at 60s interval. Effect of acotiamide 2 µM on spontaneous and carbachol evoked contractions was also assessed. RESULTS: Acotiamide 2 µM significantly enhanced the Atropine and Tetrodotoxin (TTX)-sensitive EFS evoked contractions of rat and human bladder at 8-32 Hz (Two-way ANOVA followed Sidak's multiple comparison; *p < 0.01) and on repeat 10 Hz stimulation (Paired Student's t-test; *p < 0.05), while producing a modest effect on the spontaneous contractions and a negligible effect on the carbachol evoked contractions. CONCLUSIONS: Enhancement of TTX-sensitive evoked contractions of rat and human bladder by acotiamide is consistent with the enhancement of excitatory neuro-effector transmission mainly through prejunctional mechanisms. Findings highlight immense therapeutic potential of antimuscarinics with low M3 receptor affinity like acotiamide in Underactive bladder (UAB)/DU treatment.


Assuntos
Benzamidas/uso terapêutico , Tiazóis/uso terapêutico , Bexiga Inativa/tratamento farmacológico , Bexiga Urinária/patologia , Animais , Benzamidas/química , Benzamidas/farmacologia , Carbacol/farmacologia , Estimulação Elétrica , Humanos , Masculino , Contração Muscular/efeitos dos fármacos , Ratos Sprague-Dawley , Tiazóis/química , Tiazóis/farmacologia , Bexiga Urinária/efeitos dos fármacos , Bexiga Urinária/inervação
18.
BMC Med Genet ; 21(1): 141, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32611331

RESUMO

BACKGROUND: Lynch syndrome (LS), which is known as a hereditary cancer syndrome, is distinguished by microsatellite instability, represented by the altered number of repetitive sequences in the coding and/or non-coding region. Immunohistochemical staining (IHC) of DNA mismatch repair (MMR) proteins (e.g., MLH1, MSH2, MSH6, and PMS2) has been recognized as an useful technique for screening of LS. Previous study has shown that the assessment of IHC, however, requires specific caution due to variable staining patterns even without germline mutations in MMR genes. CASE PRESENTATION: A 48-year-old man, who had been treated for anaplastic astrocytoma, was referred to our department for the precise examination of progressing anemia. Whole-body examination revealed two advanced carcinomas in descending colon and stomach. A hypo-vascular mass lesion was detected in liver as well. Pathological diagnosis (on surgical specimens) was poorly differentiated adenocarcinoma in descending colon, moderately differentiated tubular adenocarcinoma in stomach, and liver metastasis, which is possibly from colon. It was suspected that this case would be Turcot's syndrome-type-1 due to its specific family history having two cases of colon cancer within the second relatives. Pathogenic frameshift mutations in codon 618 of MLH1 gene was identified. Immunohistochemical analyses (IHC) demonstrated complete loss of MLH1 immuno-expression as well as of PMS2 except for those in brain tumor. Although frameshift mutation was not found in MSH6 gene, histological expression of MSH6 was patchy in primary colon carcinoma and was completely lost in the metastatic site in liver. MSH6 expression in gastric carcinoma, a coincidental cancer in this case, was intact. An abnormal (C)8 region was identified by the cloned PCR of colon and liver tumors but not from gastric cancer. Frameshift mutation in a (C)8 tract in exon 5 of the MSH6 gene was also detected in liver metastasis. CONCLUSION: This case supports a plausible mechanism, proposed by a previous literature, for the reduced expression of MSH6 in a somatic mutation manner, which might preferentially happen in colon cancer rather than in stomach carcinoma in MLH1/PMS2-deficient type of Turcot's syndrome type 1.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias do Colo/genética , Neoplasias Colorretais/genética , Proteínas de Ligação a DNA/imunologia , Predisposição Genética para Doença , Neoplasias Hepáticas/secundário , Mutação/genética , Síndromes Neoplásicas Hereditárias/genética , Adulto , Sequência de Bases , Reparo de Erro de Pareamento de DNA/genética , Feminino , Humanos , Masculino , Repetições de Microssatélites/genética , Pessoa de Meia-Idade , Linhagem
19.
PLoS One ; 15(6): e0235137, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32603367

RESUMO

Indirect reciprocity is one of the major mechanisms in the evolution of human cooperation. In indirect reciprocity, social norms with which individuals distinguish good people from bad people play essential roles. Despite extensive studies on the evolution of cooperation in indirect reciprocity, little is known about which social norms people actually adopt. Here we reveal what kind of norms are adopted by people in indirect reciprocal situations in daily life by using scenario-based experiments. The results showed that people evaluated "justified defection" as neither good nor bad and withheld their evaluation. Theoretically, social norms that evaluate justified defection as good are required for cooperation to be stable. However, the norm that people actually adopted deviates from the theoretical predictions. Our results indicate the necessity to reconsider the justification of "justified defection" in the evolution of cooperation.


Assuntos
Comportamento Cooperativo , Modelos Psicológicos , Adulto , Evolução Biológica , Feminino , Humanos , Relações Interpessoais , Japão , Masculino , Pessoa de Meia-Idade , Normas Sociais
20.
Int J Surg Case Rep ; 71: 327-330, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32492645

RESUMO

INTRODUCTION: We experienced an extremely rare case of gastric adenocarcinoma wrapped by leiomyoma. PRESENTATION OF CASE: A 65-year-old man had an abnormality (filling defect) of the upper gastrointestinal series in his first medical checkup five years prior. Esophagogastroduodenoscopy detected a 10 mm submucosal tumor-like lesion in the greater curvature of the upper gastric remnant body. Despite repeated biopsy from the lesion, there was no sign of malignancy. A delle was observed on the top of the tumor at another visit five year after the first and a biopsy specimen revealed poorly differentiated adenocarcinoma. Therefore, laparoscopic gastrectomy was performed. Histological assessment revealed a 28 × 22 mm elevated lesion with a slight depression. Microscopically, papillary adenocarcinoma was observed at the submucosa with a solitary heterotopic gastric gland adjacent to the lesion. The final diagnosis was papillary adenocarcinoma arising from a solitary heterotopic gastric gland in the leiomyoma. No recurrence has occurred during a follow-up of two and a half years after surgery. CONCLUSIONS: This is the first report of gastric adenocarcinoma arising from a submucosal tumor.

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