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1.
World J Cardiol ; 16(5): 274-281, 2024 May 26.
Article de Anglais | MEDLINE | ID: mdl-38817650

RÉSUMÉ

BACKGROUND: Mitral valvuloplasty using artificial chordae tendineae represents an effective surgical approach for treating mitral regurgitation. Achieving precise measurements of artificial chordae tendineae length (CL) is an important factor in the procedure; however, no objective index currently exists to facilitate this measurement. Therefore, preoperative assessment of CL is critical for surgical planning and support. Four-dimensional x-ray micro-computed tomography (4D-CT) may be useful for accurate CL measurement considering that it allows for dynamic three-dimensional (3D) evaluation compared to that with transthoracic echocardiography, a conventional inspection method. AIM: To investigate the behavior and length of mitral chordae tendineae during systole using 4D-CT. METHODS: Eleven adults aged > 70 years without mitral valve disease were evaluated. A 64-slice CT scanner was used to capture 20 phases in the cardiac cycle in electrocardiographic synchronization. The length of the primary chordae tendineae was measured from early systole to early diastole using the 3D image. The primary chordae tendineae originating from the anterior papillary muscle and attached to the A1-2 region and those from the posterior papillary muscle and attached to the A2-3 region were designated as cA and cP, respectively. The behavior and maximum lengths [cA (ma), cP (max)] were compared, and the correlation with body surface area (BSA) was evaluated. RESULTS: In all cases, the mitral anterior leaflet chordae tendineae could be measured. In most cases, the cA and cP chordae tendineae could be measured visually. The mean cA (max) and cP (max) were 20.2 mm ± 1.95 mm and 23.5 mm ± 4.06 mm, respectively. cP (max) was significantly longer. The correlation coefficients (r) with BSA were 0.60 and 0.78 for cA (max) and cP (max), respectively. Both cA and cP exhibited constant variation in CL during systole, with a maximum 1.16-fold increase in cA and a 1.23-fold increase in cP from early to mid-systole. For cP, CL reached a plateau at 15% and remained elongated until end-systole, whereas for cA, after peaking at 15%, CL shortened slightly and then moved toward its peak again as end-systole approached. CONCLUSION: The study suggests that 4D-CT is a valuable tool for accurate measurement of both the length and behavior of chordae tendineae within the anterior leaflet of the mitral valve.

2.
World J Surg Oncol ; 22(1): 74, 2024 Mar 04.
Article de Anglais | MEDLINE | ID: mdl-38433196

RÉSUMÉ

BACKGROUND: Gastric cancer is primarily treated by surgery; however, little is known about the changes in the intraperitoneal immune environment and the prognostic impact of surgery. Surgical stress and cancer-associated inflammation cause immune cells to mobilize into the abdominal cavity via numerous cytokines. One such cytokine, CX3CR1, has various immune-related functions that remain to be fully explained. We characterized the intraperitoneal immune environment by investigating CX3CR1+ cells in intraperitoneal lavage fluid during gastric cancer surgery. METHODS: Lavage fluid samples were obtained from a total of 41 patients who underwent gastrectomy. The relative expression of various genes was analyzed using quantitative real-time PCR. The association of each gene expression with clinicopathological features and surgical outcomes was examined. The fraction of CX3CR1+ cells was analyzed by flow cytometry. Cytokine profiles in lavage fluid samples were investigated using a cytometric beads array. RESULTS: CX3CR1high patients exhibited higher levels of perioperative inflammation in blood tests and more recurrences than CX3CR1low patients. CX3CR1high patients tended to exhibit higher pathological T and N stage than CX3CR1low patients. CX3CR1 was primarily expressed on myeloid-derived suppressor cells and tumor-associated macrophages. In particular, polymorphonuclear myeloid-derived suppressor cells were associated with perioperative inflammation, pathological N, and recurrences. These immunosuppressive cells were associated with a trend toward unfavorable prognosis. Moreover, CX3CR1 expression was correlated with programmed death-1 expression. CONCLUSIONS: Our results suggest that CX3CR1+ cells are associated with an acute inflammatory response, tumor-promotion, and recurrence. CX3CR1 expression could be taken advantage of as a beneficial therapeutic target for improving immunosuppressive state in the future. In addition, analysis of intra-abdominal CX3CR1+ cells could be useful for characterizing the immune environment after gastric cancer surgery.


Sujet(s)
Cavité abdominale , Tumeurs de l'estomac , Humains , Tumeurs de l'estomac/chirurgie , Gastrectomie , Cytokines , Immunosuppresseurs , Inflammation , Récepteur-1 de la chimiokine CX3C
3.
J Phys Ther Sci ; 35(9): 633-637, 2023 Sep.
Article de Anglais | MEDLINE | ID: mdl-37670761

RÉSUMÉ

[Purpose] Behavioral analysis is widely used in animal research. However, such analysis requires specialized equipment and can be difficult to perform. Therefore, this study aimed to explore and validate a simple behavioral analysis method. [Participants and Methods] For behavioral assessments, Wistar rats were placed in a rearing cage and videotaped from two directions: overhead and side view. The filmed videos were analyzed using ImageJ software to calculate the distance traveled and activity and inactivity times of the rats. Intraclass correlation coefficients 1 and 2 were calculated to examine the reliability of the behavioral analysis method. [Results] Intraclass correlation coefficients 1 and 2 for distance traveled and activity and inactivity times determined using the behavioral analysis method showed high reliability. [Conclusion] The behavioral analysis method validated in this study used inexpensive and easily accessible equipment and devices. The results show high correlation coefficients for the measurement of distance traveled and activity time performed by experimental animals, demonstrating the reliability of this simple method.

4.
J Atheroscler Thromb ; 30(12): 1927-1949, 2023 Dec 01.
Article de Anglais | MEDLINE | ID: mdl-37532570

RÉSUMÉ

AIMS: MND-2119 is a novel once-daily dose self-emulsifying formulation of highly purified eicosapentaenoic acid ethyl ester (EPA-E) and is approved as an antihyperlipidemia agent in Japan. It has improved absorption and achieves higher plasma EPA concentrations at Cmax than conventional EPA-E. In the JELIS trial, concomitant use of EPA-E with statin therapy significantly reduced atherosclerotic cardiovascular disease (ASCVD) risks. As a potential mechanism of action of EPA, endogenous formation of EPA-derived anti-inflammatory metabolites is receiving greater attention. This study aims to investigate the endogenous formation of EPA-derived anti-inflammatory metabolites following single and multiple administrations of MND-2119. METHODS: Healthy adult male subjects were randomly assigned to a nonintervention (control) group, MND-2119 2-g/day group, MND-2119 4-g/day group, or EPA-E 1.8-g/day group for 7 days (N=8 per group). Plasma fatty acids and EPA-derived metabolites were evaluated. Peripheral blood neutrophils were isolated, and the production of EPA-derived metabolites from in vitro stimulated neutrophils was evaluated. RESULTS: After single and multiple administrations of MND-2119 2 g/day, there were significant increases in plasma EPA concentration, 18-hydroxyeicosapentaenoic acid (18-HEPE), and 17,18-epoxyeicosatetraenoic acid compared with those of EPA-E 1.8 g/day. They were further increased with MND-2119 4 g/day administration. In neutrophils, the EPA concentration in the MND-2119 2-g/day group was significantly higher compared with that in the EPA-E 1.8-g/day group after multiple administration, and 18-HEPE production was positively correlated with EPA concentration. No safety issues were noted. CONCLUSIONS: These results demonstrate that MND-2119 increases the plasma and cellular concentrations of EPA and EPA-derived metabolites to a greater extent than conventional EPA-E formulations.


Sujet(s)
Acide docosahexaénoïque , Esters , Adulte , Humains , Mâle , Acide eicosapentanoïque , Acides gras , Anti-inflammatoires , Administration par voie orale
5.
Viruses ; 15(7)2023 06 23.
Article de Anglais | MEDLINE | ID: mdl-37515109

RÉSUMÉ

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious and continues to spread worldwide. To avoid the spread of infection, it is important to control its transmission routes. However, as methods to prevent airborne infections are lacking, people are forced to take measures such as keeping distance from others or wearing masks. Here, we evaluate the antiviral activity of propylene glycol (PG), which is safe, odorless, and volatile. PG showed pronounced antiviral activity against the influenza virus (IAV) at concentrations above 55% in the liquid phase. Given its IAV inactivation mechanism, which involves increasing the fluidity of the viral membrane, PG is expected to have a broad effect on enveloped viruses. PG showed antiviral activity against SARS-CoV-2. We also developed a system to evaluate the antiviral effect of PG in spray and volatilized forms. PG was found to be effective against aerosol IAV in both forms; the effective PG concentration against IAV in the vapor phase was 87 ppmv (0.27 mg/L). These results demonstrate that PG is an effective means for viral inactivation in various situations for infection control. This technology is expected to control the spread of current and future infectious diseases capable of causing outbreaks and pandemics.


Sujet(s)
Antiviraux , COVID-19 , Humains , Antiviraux/pharmacologie , Antiviraux/usage thérapeutique , SARS-CoV-2 , Gouttelettes et aérosols respiratoires , Propylène glycols
6.
Biomed Pharmacother ; 165: 115079, 2023 Sep.
Article de Anglais | MEDLINE | ID: mdl-37413906

RÉSUMÉ

Canine primary lung cancer (cPLC) is a rare malignant tumor in dogs, and exhibits poor prognosis. Effective therapeutic drugs against cPLC have not been established yet. Also, cPLC resembles human lung cancer in histopathological characteristics and gene expression profiles and thus could be an important research model for this disease. Three-dimensional organoid culture is known to recapitulate the tissue dynamics in vivo. We, therefore, tried to generate cPLC organoids (cPLCO) for analyzing the profiles of cPLC. After samples from cPLC and the corresponding normal lung tissue were collected, cPLCO were successfully generated, which recapitulated the tissue architecture of cPLC, expressed lung adenocarcinoma marker (TTF1), and exhibited tumorigenesis in vivo. The sensitivity of cPLCO to anti-cancer drugs was different among strains. RNA-sequencing analysis showed significantly upregulated 11 genes in cPLCO compared with canine normal lung organoids (cNLO). Moreover, cPLCO were enriched with the MEK-signaling pathway compared with cNLO. The MEK inhibitor, trametinib decreased the viability of several strains of cPLCO and inhibited the growth of cPLC xenografts. Collectively, our established cPLCO model might be a useful tool for identifying novel biomarkers for cPLC and a new research model for dog and human lung cancer.


Sujet(s)
Adénocarcinome pulmonaire , Tumeurs du poumon , Pneumologie , Humains , Chiens , Animaux , , Adénocarcinome pulmonaire/traitement médicamenteux , Adénocarcinome pulmonaire/génétique , Adénocarcinome pulmonaire/métabolisme , Tumeurs du poumon/traitement médicamenteux , Tumeurs du poumon/génétique , Tumeurs du poumon/anatomopathologie , Organoïdes , Mitogen-Activated Protein Kinase Kinases/métabolisme
7.
Cancer Sci ; 114(5): 1846-1858, 2023 May.
Article de Anglais | MEDLINE | ID: mdl-36748311

RÉSUMÉ

Tumor-resident memory T (TRM ) cells in primary tumors are reportedly associated with a favorable prognosis in several malignancies. However, the behaviors and functions of TRM cells in regional lymph nodes (LNs) of esophageal cancer remain poorly understood. The aim of this study was to elucidate the effects of TRM cells in regional LNs of esophageal cancer on clinicopathological findings and prognosis. Specimens of esophageal cancer and primary metastatic LNs (recurrent nerve LNs) were obtained from 84 patients who underwent radical esophagectomy between 2011 and 2017. We performed immunohistochemistry to enumerate and analyze TRM cells, and used flow cytometry to investigate the function of TRM cells. TRM cells were observed in both metastatic LNs and primary tumors. TRM cell-rich specimens exhibited reduced lymphatic invasion and LN metastasis and prolonged survival compared with TRM cell-poor specimens. TRM cells in metastatic LNs were more significantly associated with enhanced survival than TRM cells in primary tumors. TRM cells expressed high levels of granzyme B as a cytotoxicity marker. Our results suggested that high TRM cell infiltration in metastatic LNs improves survival even though LN metastasis is commonly associated with poor prognosis. TRM cells possibly contribute to antitumor immunity in regional LNs.


Sujet(s)
Tumeurs de l'oesophage , Carcinome épidermoïde de l'oesophage , Humains , Carcinome épidermoïde de l'oesophage/chirurgie , Carcinome épidermoïde de l'oesophage/anatomopathologie , Pronostic , Tumeurs de l'oesophage/anatomopathologie , Cellules T mémoire , Noeuds lymphatiques/anatomopathologie , Oesophagectomie , Lymphadénectomie , Études rétrospectives , Stadification tumorale
8.
Clin Pharmacol Drug Dev ; 12(1): 107-115, 2023 01.
Article de Anglais | MEDLINE | ID: mdl-36205347

RÉSUMÉ

MND-2119 is a self-emulsifying formulation of highly purified eicosapentaenoic acid ethyl ester (EPA-E) designed to be administered once daily due to improved absorption compared with the nonself-emulsifying formulation. In these studies, MND-2119 was administered to healthy adult males in single or multiple doses. In the single administration study, MND-2119 (0.5-4 g) was administered under fed and fasted conditions to evaluate MND-2119 pharmacokinetics and safety under these conditions. This study showed that Cmax and AUC0-72h of plasma EPA concentration after single administration were higher under fed conditions than under fasted conditions, for all doses. In the multiple administration study, subjects received either MND-2119 (0.5-4 g) immediately after breakfast or EPA-E (0.9 g) immediately after breakfast and dinner for 11 days to compare pharmacokinetics and safety of MND-2119 to EPA-E. In this study, the rate of rise in Cmin of the plasma EPA concentration with MND-2119 decreased from days 6 to 8 after administration and was thought to have reached a steady state on day 11. The mean Css,max of MND-2119 administered as 1 g once daily, and the mean Css,min and the mean AUCss,0-24h of MND-2119 administered as 2 g once daily were higher than those of EPA-E administered as 0.9 g twice daily. No safety-related issues occurred in either study. These results suggest that MND-2119 administered once daily may achieve equivalent or higher plasma EPA concentrations compared to the nonself-emulsifying formulation administered twice daily.


Sujet(s)
Acide eicosapentanoïque , Jeûne , Adulte , Humains , Mâle , Biodisponibilité , Administration par voie orale
9.
JMA J ; 5(4): 520-527, 2022 Oct 17.
Article de Anglais | MEDLINE | ID: mdl-36407078

RÉSUMÉ

Introduction: This study assessed changes in patients transported to an emergency and critical care center before and after the coronavirus disease 2019 (COVID-19) pandemic in Japan and examined problems that should be addressed in emergency medical care. Methods: This single-center retrospective observational study was conducted at a university hospital. The subjects were patients who were transported to a "tertiary emergency department" receiving advanced medical care. With January 16, 2020, as the cutoff date, 4,197 patients who were transported to the hospital from January 16, 2019, to January 15, 2021, were recruited. The patients were classified into nine disease groups using the International Classification of Diseases, Tenth Revision. The emergency department (ED) visit count in 2020 was compared with that in 2019 using Poisson regression. Results: The number of patients transported to the tertiary ED in 2020 decreased by 7.8% compared with that in 2019. The number of patients transported to the tertiary ED decreased compared with that in the previous year during the period when the number of confirmed COVID-19 cases in Japan increased and showed the opposite trend when the number of confirmed cases decreased. As per diagnostic classification, it decreased for all diagnoses except External causes, and significant decreases were observed in Infectious (47.5%), Non-COVID-19 respiratory (28.4%), and Trauma (25.2%). In External causes, the rate of change for suicide cases alone increased to 43.2%. Conclusions: While the number of confirmed cases increased, the number of tertiary ED patients associated with COVID-19 decreased temporarily. It is necessary to fully consider the burden on medical institutions 1-2 months after the number of infected people peaks. It is also necessary to closely monitor suicides associated with COVID-19 as a factor that will cause changes in emergency medical care in the future.

10.
J Clin Lipidol ; 16(5): 737-746, 2022.
Article de Anglais | MEDLINE | ID: mdl-36202740

RÉSUMÉ

BACKGROUND: In Japan, eicosapentaenoic acid ethyl ester (EPA-E) is administered twice-daily or three-times-daily for dyslipidemia. We have developed MND-2119, a novel self-emulsifying formulation of highly purified EPA-E which can be administered once-daily. OBJECTIVE: The objective of this study was to investigate the safety and efficacy of long-term administration of MND-2119 in hypertriglyceridemia patients. METHODS: In this multicenter, 52-week, open-label study, patients with high triglyceride (TG) (TG levels between ≥ 150 and < 500 mg/dL) undergoing lifestyle modification were randomized to MND-2119 2 g/day (n=61) or MND-2119 4 g/day (n=61). RESULTS: The incidence of adverse events in MND-2119 2 g/day and MND-2119 4 g/day was 70.5% and 62.3%, respectively, and the incidence of adverse drug reactions was 9.8% and 8.2%, respectively. There were no notable problems in the safety assessments of both treatment groups. By Week 4, TG levels had decreased from baseline in both groups, and the TG reducing effect continued up to Week 52 (mean percentage change from baseline in TG at Week 52 [two-sided 95% confidence interval]: MND-2119 2 g/day: -16.71% [-26.61, -6.81], MND-2119 4 g/day: -21.01% [-27.86, -14.16]). In both groups, plasma EPA concentration at Week 4 was maintained up until Week 52 and the plasma EPA concentration at Week 52 was 200.5 ± 54.7 µg/mL in MND-2119 2 g/day and 308.6 ± 98.6 µg/mL in MND-2119 4 g/day. CONCLUSION: Long-term administration of MND-2119 was not associated with any safety-related problems. TG levels decreased by Week 4, and the TG reducing effect continued up to Week 52.


Sujet(s)
Acide eicosapentanoïque , Hypertriglycéridémie , Humains , Méthode en double aveugle , Acide eicosapentanoïque/effets indésirables , Triglycéride
11.
Int J Mol Sci ; 23(18)2022 Sep 14.
Article de Anglais | MEDLINE | ID: mdl-36142607

RÉSUMÉ

Long non-coding RNAs (lncRNAs) play critical roles in human cancers. HOXA11 anti-sense RNA (HOXA11-AS) is an lncRNA belonging to the homeobox (HOX) gene cluster that promotes liver metastasis in human colon cancer. However, its role and mechanism of action in human oral squamous cell carcinoma (OSCC) are unclear. In this study, we investigated HOXA11-AS expression and function in human OSCC tissues and cell lines, as well as a mouse model of OSCC. Our analyses showed that HOXA11-AS expression in human OSCC cases correlates with lymph node metastasis, nicotinamide adenine dinucleotide (NAD)(P)H: quinone oxidoreductase 1 (NQO1) upregulation, and dihydronicotinamide riboside (NRH): quinone oxidoreductase 2 (NQO2) downregulation. Using the human OSCC cell lines HSC3 and HSC4, we demonstrate that HOXA11-AS promotes NQO1 expression by sponging microRNA-494. In contrast, HOXA11-AS recruits zeste homolog 2 (EZH2) to the NQO2 promoter to suppress its expression via the trimethylation of H3K27. The upregulation of NQO1 enzymatic activity by HOXA11-AS results in the consumption of flavin adenine dinucleotide (FAD), which reduces FAD-requiring glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity and suppresses glycolysis. However, our analyses show that lactic acid fermentation levels are preserved by glutaminolysis due to increased malic enzyme-1 expression, promoting enhanced proliferation, invasion, survival, and drug resistance. In contrast, suppression of NQO2 expression reduces the consumption of NRH via NQO2 enzymatic activity and increases NAD levels, which promotes enhanced stemness and metastatic potential. In mouse tumor models, knockdown of HOXA11-AS markedly suppressed tumor growth and lung metastasis. From these findings, targeting HOXA11-AS may strongly suppress high-grade OSCC by regulating both NQO1 and NQO2.


Sujet(s)
Carcinome épidermoïde , Protéines à homéodomaine/métabolisme , microARN , Tumeurs de la bouche , NADPH dehydrogenase (quinone)/métabolisme , Quinone reductases/métabolisme , ARN long non codant , Animaux , Carcinome épidermoïde/génétique , Carcinome épidermoïde/anatomopathologie , Lignée cellulaire tumorale , Prolifération cellulaire , Flavine adénine dinucléotide/génétique , Gènes homéotiques , Glyceraldehyde 3-phosphate dehydrogenases/génétique , Humains , Acide lactique , Souris , microARN/génétique , Tumeurs de la bouche/génétique , Tumeurs de la bouche/anatomopathologie , NAD/génétique , Quinones , ARN antisens , ARN long non codant/génétique , ARN long non codant/métabolisme , Carcinome épidermoïde de la tête et du cou/génétique
12.
J Clin Lipidol ; 16(5): 704-714, 2022.
Article de Anglais | MEDLINE | ID: mdl-35871058

RÉSUMÉ

BACKGROUND: In Japan, eicosapentaenoic acid ethyl ester (EPA-E) is administered twice-daily or three-times-daily for dyslipidemia. We have developed MND-2119, a novel self-emulsifying formulation of highly purified EPA-E, which can be administered once-daily. OBJECTIVE: The objective of this study was to assess non-inferiority in the efficacy of MND-2119 in patients with hypertriglyceridemia compared with highly purified EPA-E. METHODS: In this multicenter, 12-week, double-blind study, patients with high triglyceride (TG levels between ≥ 150 and < 500 mg/dL) undergoing lifestyle modification were randomized to MND-2119 2 g/day (n=145), MND-2119 4 g/day (n=145), EPA-E 1.8 g/day (n=145) or EPA-E 2.7 g/day (n=145). The primary endpoint was percentage change in TG levels from baseline to end of treatment. RESULTS: MND-2119 2, 4 g/day and EPA-E 1.8, 2.7 g/day reduced TG levels from baseline by -10.09%, -15.51%, -9.30%, and -8.80%, respectively. The TG reduction rate of MND-2119 2 g/day was non-inferior to that of EPA-E 1.8 g/day (LS mean difference: -0.42, 95%CI: -5.76 to 4.91). Moreover, the TG reduction rate of MND-2119 4 g/day was superior to that of MND-2119 2 g/day (LS mean difference: -5.74, 95%CI: -10.59 to -0.89). There were no remarkable safety differences between MND-2119 2 g/day and EPA-E 1.8 g/day and between MND-2119 4 g/day and EPA-E 2.7 g/day. CONCLUSION: Non-inferiority of MND-2119 2 g/day to EPA-E 1.8 g/day for efficacy, and superiority of MND-2119 4 g/day over MND-2119 2 g/day for efficacy were verified. MND-2119 was safe and well tolerated.


Sujet(s)
Acide eicosapentanoïque , Hypertriglycéridémie , Humains , Méthode en double aveugle , Acide eicosapentanoïque/effets indésirables , Hypertriglycéridémie/traitement médicamenteux , Triglycéride
13.
Int J Mol Sci ; 23(12)2022 Jun 10.
Article de Anglais | MEDLINE | ID: mdl-35742959

RÉSUMÉ

The tight junction (TJ) protein claudin-4 (CLDN4) is overexpressed in bladder urothelial carcinoma (BUC) and correlates with cancer progression. However, the mechanism of CLDN4 upregulation and promotion of malignant phenotype is not clear. Here, we analyzed 157 cases of BUC and investigated the hypomethylation of CpG island in the CLDN4 promoter DNA and its correlation with cancer progression. In hypomethylated cases, CLDN4 expression, cell proliferation, stemness, and epithelial-mesenchymal transition were increased. Treatment of three human BUC cell lines with the demethylating agent aza-2'-deoxycytidine (AZA) led to excessive CLDN4 expression, and, specifically, to an increase in CLDN4 monomer that is not integrated into the TJ. The TJ-unintegrated CLDN4 was found to bind integrin ß1 and increase stemness, drug resistance, and metastatic ability of the cells as well as show an anti-apoptosis effect likely via FAK phosphorylation, which reduces upon knockdown of CLDN4. Thus, CLDN4 is overexpressed in BUC by an epigenetic mechanism and the high expression enhances the malignant phenotype of BUC via increased levels of TJ-unintegrated CLDN4. CLDN4 promoter DNA methylation is expected to be a novel indicator of BUC malignant phenotype and a new therapeutic target.


Sujet(s)
Carcinome transitionnel , Tumeurs de la vessie urinaire , Carcinome transitionnel/génétique , Lignée cellulaire tumorale , Claudine-4/génétique , Claudine-4/métabolisme , Méthylation de l'ADN , Humains , Phénotype , Tumeurs de la vessie urinaire/génétique
14.
BMC Cancer ; 22(1): 699, 2022 Jun 24.
Article de Anglais | MEDLINE | ID: mdl-35751038

RÉSUMÉ

BACKGROUND: Tertiary lymphoid structures (TLSs) have been reported to be involved in immune responses in many carcinomas. This study investigated the significance of TLSs in esophageal squamous cell carcinoma, focusing on TLS maturation.  METHODS: The relationships of TLSs with clinicopathological features of 236 patients who underwent curative surgery for stage 0-IV esophageal squamous cell carcinoma were investigated. Mature TLSs, in which the germinal center formation was rich in CD23+ cells, were classified as TLSs containing a germinal center (GC-TLSs). GC-TLS densities were measured, and CD8+ cells were counted. The prognostic impact of GC-TLSs was assessed by Kaplan-Meier plots using the log-rank test for the relapse-free survival. A comparative study of GC-TLSs was performed using the Wilcoxon rank sum test. The relationship between GC-TLSs and CD8+ cells was examined by Spearman's rank correlation coefficient test. RESULTS: TLSs were located mainly at the invasive margin of the tumor in cases with esophageal squamous cell carcinoma. Among the patients treated with neoadjuvant chemotherapy, those with advanced disease had a better prognosis in the GC-TLS high-density group than did those in the GC-TLS low-density group. Patients in whom neoadjuvant chemotherapy was effective had more GC-TLSs than those in whom it was less effective. The density of GC-TLSs and the number of tumor-infiltrating CD8+ cells were higher in patients treated with neoadjuvant chemotherapy than in those without chemotherapy, and a weak correlation between the density of GC-TLSs and the number of tumor-infiltrating CD8+ cells was observed. Moreover, co-culturing of PBMCs with an anticancer drug-treated esophageal squamous cell carcinoma cell line increased the CD20 and CD23 expression in PBMCs in vitro. CONCLUSION: TLS maturation may be important for evaluating the local tumor immune response in patients treated with neoadjuvant chemotherapy for esophageal squamous cell carcinoma. The present results suggest that TLS maturation may be a useful target for predicting the efficacy of immunotherapy, including immune checkpoint inhibitor treatment for esophageal squamous cell carcinoma.


Sujet(s)
Tumeurs de l'oesophage , Carcinome épidermoïde de l'oesophage , Structures lymphoïdes tertiaires , Tumeurs de l'oesophage/anatomopathologie , Carcinome épidermoïde de l'oesophage/anatomopathologie , Humains , Lymphocytes TIL , Récidive tumorale locale/anatomopathologie , Pronostic , Structures lymphoïdes tertiaires/métabolisme , Structures lymphoïdes tertiaires/anatomopathologie , Microenvironnement tumoral
15.
Cancer Diagn Progn ; 2(3): 384-390, 2022.
Article de Anglais | MEDLINE | ID: mdl-35530656

RÉSUMÉ

BACKGROUND/AIM: Recently, several studies have reported that CD103 +  T cells are associated with antitumor immunity in gastric cancer (GC). However, the significance of CD103 +  T cells in Borrmann type 4 GC remains unclear. The aim of this study is to assess the association of CD103 + T cells with type 4 GC. MATERIALS AND METHODS: Tissue samples obtained from surgically resected specimens of patients with type 4 GC were collected, and immunohistochemical staining was performed to detect the presence of CD103 + T cells. RESULTS: A total of 46 patients were analyzed. In some patients, high CD103 expression was observed, and patients with high CD103 expression tended to have a better prognosis than those with low CD103 expression. In particular, for patients who receive doublet chemotherapy after surgery, high CD103 expression was associated with a good prognosis. CONCLUSION: CD103 + T cells may be a prognostic marker in type 4 GC.

16.
Pol J Radiol ; 87: e177-e180, 2022.
Article de Anglais | MEDLINE | ID: mdl-35505856

RÉSUMÉ

Purpose: Computed tomography (CT)-guided percutaneous drainage has been used to address pelvic abscesses because it is safe and minimally invasive. However, CT-guided drainage has the limitation that the puncture route should be on the same axial slice. A technique for puncturing in the cranio-caudal direction under CT fluoroscopy is needed. Case report: An 82-year-old man with an abscess due to rectal cancer was scheduled for CT-guided drainage to improve his general condition before radical surgery. Drainage was performed via a perineal approach to localize the drainage tract in the resection area to avoid dissemination of cancer cells. To perform a puncture in the cranio-caudal direction we controlled the needle like a joystick and advanced it under CT fluoroscopy while moving the CT gantry cranially to follow the needle tip throughout the puncture. Our unique technique yielded successful CT-guided puncture in the cranio-caudal direction. Conclusions: Our unique technique overcomes the limitations of CT-guided cranio-caudal puncture and may allow the drainage of abscesses whose treatment was heretofore difficult.

17.
Br J Cancer ; 127(2): 350-363, 2022 07.
Article de Anglais | MEDLINE | ID: mdl-35365766

RÉSUMÉ

BACKGROUND: The naturally occurring amino acid 5-aminolevulinic acid (5-ALA) is a precursor of protoporphyrin IX (PpIX) biosynthesised in the mitochondria. When accumulated PpIX is excited by light (wavelength of 625-635 nm), reactive oxygen species (ROS) are generated. Here, we investigated whether 5-ALA may increase the sensitisation of prostate cancer (PCA) cells to radiotherapy through the generation of ROS via its metabolite, PpIX. METHODS: Effect of 5-ALA on PC-3 and DU-145 PCA cell lines treated with ionising radiation (IR) was examined in vitro and in vivo with assessment by clonogenic assay, mitochondrial function and ROS production under normoxia or hypoxia condition. RESULTS: 5-ALA enhanced intra-mitochondrial ROS production immediately after exposure to IR and decreased mitochondrial membrane potential via increase of intra-cellular PpIX. IR with 5-ALA induced mitochondrial dysfunction and increased ATP production, switching energy metabolism to the quiescence. Under hypoxic condition, ROS burst and mitochondrial dysfunction were induced by IR with 5-ALA resulting reducing cancer stemness and radiation resistance. CONCLUSION: These results suggest that combined therapy with 5-ALA and radiation therapy is a novel strategy to improve the anti-cancer effects of radiation therapy for PCA.


Sujet(s)
Photothérapie dynamique , Tumeurs de la prostate , Acide amino-lévulinique/pharmacologie , Acide amino-lévulinique/usage thérapeutique , Lignée cellulaire tumorale , Humains , Hypoxie , Mâle , Mitochondries/métabolisme , Photothérapie dynamique/méthodes , Photosensibilisants/usage thérapeutique , Tumeurs de la prostate/métabolisme , Protoporphyrines/métabolisme , Protoporphyrines/pharmacologie , Espèces réactives de l'oxygène/métabolisme
18.
Sci Rep ; 12(1): 6636, 2022 04 22.
Article de Anglais | MEDLINE | ID: mdl-35459785

RÉSUMÉ

The oral cavity is an entrance for respiratory viruses, such as influenza. Recently, saliva has been shown to exert both antimicrobial and antiviral activities. Thus, saliva may be a biological factor that contributes to the prevention of influenza infection. However, the actual salivary anti-influenza A virus (IAV) activity in individuals and its determinant factors are unknown. By assessing individual variations in salivary anti-IAV activity in 92 people using an established new high-throughput system in this study, we found that the anti-IAV activity varied widely between individuals and showed a significant positive correlation with protein-bound sialic acid (BSA) level (ρ = 0.473; p < 0.001). Furthermore, the anti-IAV activity of saliva with enzymatically reduced BSA content was significantly lower. These results indicate that BSA is a direct regulator of salivary anti-IAV activity and is a determinant of individual differences. Additionally, after comparing the anti-IAV activity across the groups by age, anti-IAV activity in young people (aged 5-19 years) were lower than in adults aged 20-59 years and elderly people aged 60-79 years. Our study suggests that BSA levels in saliva may be important in preventing influenza infection.


Sujet(s)
Grippe humaine , Orthomyxoviridae , Adolescent , Adulte , Sujet âgé , Antiviraux/pharmacologie , Humains , Acide N-acétyl-neuraminique , Salive
19.
PLoS One ; 17(1): e0262455, 2022.
Article de Anglais | MEDLINE | ID: mdl-34995329

RÉSUMÉ

Nivolumab, an immune checkpoint blocker, has been approved for advanced gastric cancer (GC), but predictive factors of nivolumab's efficacy in patients with GC, especially immune cells such as tissue-resident memory T cells or those forming tertiary lymphoid structures (TLS), remain unclear. Tissue samples were obtained from surgically resected specimens of patients with GC who were treated with nivolumab as third-line or later treatment. Immunohistochemical staining was performed to detect the presence of TLS and CD103+ T cells and assess the association between TLSs and response to nivolumab treatment. A total of 19 patients were analyzed. In patients with partial response (PR) to nivolumab, numerous TLS were observed, and CD103+ T cells were found in and around TLS. Patients with many TLS experienced immune-related adverse events more often than those with few TLS (p = 0.018). The prognosis of patients with TLS high was better than those with TLS low. Patients with a combination of TLS high and CD103 high tended to have a better prognosis than other groups. Our results suggested that TLS status might be a predictor of nivolumab effectiveness.


Sujet(s)
Antinéoplasiques immunologiques/usage thérapeutique , Récidive tumorale locale/traitement médicamenteux , Nivolumab/usage thérapeutique , Tumeurs de l'estomac/traitement médicamenteux , Structures lymphoïdes tertiaires/traitement médicamenteux , Sujet âgé , Antigènes CD/analyse , Femelle , Humains , Intégrines alpha/analyse , Mâle , Cellules T mémoire/effets des médicaments et des substances chimiques , Cellules T mémoire/anatomopathologie , Adulte d'âge moyen , Récidive tumorale locale/diagnostic , Récidive tumorale locale/anatomopathologie , Récidive tumorale locale/chirurgie , Pronostic , Tumeurs de l'estomac/diagnostic , Tumeurs de l'estomac/anatomopathologie , Tumeurs de l'estomac/chirurgie , Structures lymphoïdes tertiaires/diagnostic , Structures lymphoïdes tertiaires/anatomopathologie , Résultat thérapeutique
20.
Juntendo Iji Zasshi ; 68(5): 481-490, 2022.
Article de Anglais | MEDLINE | ID: mdl-39081579

RÉSUMÉ

Objectives: The aim of this study was to measure the diaphragm volume using three-dimensional computed tomography (3D-CT) and verify its validity. Design: This was a retrospective study of existing samples. Methods: Participants comprised five male patients, aged 65-70 years, who underwent preoperative chest CT (with a slice thickness of 0.5 mm) before coronary artery bypass surgery. The diaphragm was selectively extracted using a workstation to reconstruct a stereoscopic image, and the total muscle volume was measured. To confirm the accuracy and reproducibility of diaphragm muscle volume measurements on CT, all cases were measured three times by two observers, and intraclass correlation coefficients (ICCs) and interobserver correlations were determined. Results: Observers #1 and #2 reported an average diaphragm volume of 256.7±33 cm3 and 259.3±36 cm3, respectively. The ICC analyses yielded Cronbach's alphas of 0.992 and 0.981 from both observers, and the interobserver correlation was 0.991. The ICC of a single measurement and the average measurement was 0.984 (95% confidence interval: 0.998-0.884) and 0.992 (95% confidence interval: 0.999-0.939), respectively. Conclusions: To our knowledge, this study is the first to standardize the method for measuring the total diaphragm volume and examine the reproducibility and validity of the new method. The diaphragm could be selectively extracted and reconstructed. Measurement of the total diaphragm muscle volume using a workstation to reconstruct a stereoscopic image is feasible and highly reproducible. This technique can be reliably employed to evaluate diaphragm volume, thickness, and morphology.

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