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1.
BMC Womens Health ; 24(1): 460, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39160498

RESUMEN

BACKGROUND: We conducted this study to clarify the magnetic resonance imaging (MRI) characteristics of lobular endocervical glandular hyperplasia (LEGH) and Nabothian cysts. METHODS: This study included 48 patients who underwent hysterectomy at our institution between 2016 and 2020 for suspected LEGH. Histopathological studies confirmed the presence of 25 Nabothian cysts and 23 cases of LEGH. We retrospectively analyzed five characteristic MRI findings: (1) located at the upper cervical canal, (2) positioned within the cervical stroma, (3) not circumscribing the cervical canal, (4) low- to iso-intensity on T1-weighted images (T1WI), and (5) "cosmos" or "microcystic" pattern. We compared the diagnostic accuracy of these findings for LEGH and Nabothian cysts using sensitivity, specificity, and predictive values. Combinations of findings were also calculated. RESULTS: The characteristics "cosmos" or "microcystic" pattern, lesion not circumscribing the cervical canal, and low/iso-intensity on T1WI had a sensitivity and specificity greater than 50%. The sensitivity was 73.9% and specificity 84.0% when a combination of "cosmos" or "microcystic" pattern and lesion not circumscribing the cervical canal was present. CONCLUSION: The coexistence of a "cosmos" or "microcystic" pattern and not circumscribing the cervical canal was the most characteristic finding that distinguished LEGH from Nabothian cysts. When neither of these findings is present, Nabothian cyst can be suspected.


Asunto(s)
Cuello del Útero , Quistes , Imagen por Resonancia Magnética , Sensibilidad y Especificidad , Humanos , Femenino , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Persona de Mediana Edad , Quistes/diagnóstico por imagen , Quistes/diagnóstico , Quistes/patología , Adulto , Cuello del Útero/patología , Cuello del Útero/diagnóstico por imagen , Anciano , Hiperplasia/diagnóstico por imagen , Hiperplasia/diagnóstico , Hiperplasia/patología , Histerectomía , Enfermedades del Cuello del Útero/diagnóstico , Enfermedades del Cuello del Útero/diagnóstico por imagen , Enfermedades del Cuello del Útero/patología , Cuidados Preoperatorios/métodos , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/diagnóstico por imagen , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugía
2.
Reprod Med Biol ; 23(1): e12580, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38756693

RESUMEN

Purpose: Decidualization is an important event for embryo implantation and successful pregnancy. Impaired decidualization leads to implantation failure and miscarriage. However, it is unclear how often decidualization failure occurs in infertile women. By analyzing the endometrium at late-secretory phase, we investigated the incidence and pathogenesis of decidualization failure among infertile women. Methods: Endometrial dating was performed on the endometria obtained in the late-secretory phase from 33 infertile women. Endometrial dating of more than 2 days delay was taken as an indication of decidualization failure. The expression of essential transcription factors for decidualization (FOXO1, WT1, and C/EBPß) was examined by immunohistochemistry. Results: Among 32 cases, 20 cases (62.5%) showed decidualization failure. These patients tended to have a history of more frequent miscarriages than those without decidualization failure. The percentage of cells that immunostained positive for the expression of three transcription factors was significantly lower in the patients with decidualization failure than in those without decidualization failure. Serum progesterone levels measured in the mid- and late-secretory phase were not significantly different between the cases with and without decidualization failure. Conclusions: The incidence of decidualization failure is high in infertile women.

3.
J Biol Chem ; 298(5): 101874, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35358514

RESUMEN

We previously reported that CCAAT/enhancer-binding protein beta (C/EBPß) is the pioneer factor inducing transcription enhancer mark H3K27 acetylation (H3K27ac) in the promoter and enhancer regions of genes encoding insulin-like growth factor-binding protein-1 (IGFBP-1) and prolactin (PRL) and that this contributes to decidualization of human endometrial stromal cells (ESCs). Peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α; PPARGC1A) is a transcriptional coactivator known to regulate H3K27ac. However, although PGC-1α is expressed in ESCs, the potential role of PGC-1α in mediating decidualization is unclear. Here, we investigated the involvement of PGC-1α in the regulation of decidualization. We incubated ESCs with cAMP to induce decidualization and knocked down PPARGC1A to inhibit cAMP-induced expression of IGFBP-1 and PRL. We found cAMP increased the recruitment of PGC-1α and p300 to C/EBPß-binding sites in the promoter and enhancer regions of IGFBP-1 and PRL, corresponding with increases in H3K27ac. Moreover, PGC-1α knockdown inhibited these increases, suggesting PGC-1α forms a histone-modifying complex with C/EBPß and p300 at these regions. To further investigate the regulation of PGC-1α, we focused on C/EBPß upstream of PGC-1α. We found cAMP increased C/EBPß recruitment to the novel enhancer regions of PPARGC1A. Deletion of these enhancers decreased PGC-1α expression, indicating that C/EBPß upregulates PGC-1α expression by binding to novel enhancer regions. In conclusion, PGC-1α is upregulated by C/EBPß recruitment to novel enhancers and contributes to decidualization by forming a histone-modifying complex with C/EBPß and p300, thereby inducing epigenomic changes in the promoters and enhancers of IGFBP-1 and PRL.


Asunto(s)
Histonas , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , AMP Cíclico/metabolismo , Regulación de la Expresión Génica , Histonas/genética , Histonas/metabolismo , Humanos , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Prolactina/genética , Prolactina/metabolismo , Células del Estroma/metabolismo
4.
J Urol ; 209(1): 187-197, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36067387

RESUMEN

PURPOSE: This study aimed to evaluate the usefulness of the LDN-PSA (LacdiNAc-glycosylated-prostate specific antigen) in detecting clinically significant prostate cancer in patients suspected of having clinically significant prostate cancer on multiparametric magnetic resonance imaging. MATERIALS AND METHODS: Patients with prostate specific antigen levels ranging between 3.0 ng/mL and 20 ng/mL and suspicious lesions with PI-RADS (Prostate Imaging-Reporting and Data System) category ≥3 were included prospectively. The LDN-PSA was measured using an automated 2-step Wisteria floribunda agglutinin lectin-anti-prostate specific antigen antibody sandwich immunoassay. RESULTS: Two hundred four patients were included. Clinically significant prostate cancer was detected in 105 patients. On multivariable logistic regression analysis, prostate specific antigen density (OR 1.61, P = .010), LDN-PSAD (OR 1.04, P = .012), highest PI-RADS category (3 vs 4, 5; OR 14.5, P < .0001), and location of the lesion with highest PI-RADS category (transition zone vs peripheral zone) (OR 0.34, P = .009) were significant risk factors for detecting clinically significant prostate cancer. Among the patients with the highest PI-RADS category 3 (n=113), clinically significant prostate cancer was detected in 28 patients. On multivariable logistic regression analysis to predict the detection of clinically significant prostate cancer in patients with the highest PI-RADS category 3, age (OR 1.10, P = .026) and LDN-PSAD (OR 1.07, P < .0001) were risk factors for detecting clinically significant prostate cancer. CONCLUSIONS: LDN-PSAD would be a biomarker for detecting clinically significant prostate cancer in patients with prostate specific antigen levels ≤20 ng/mL and suspicious lesions with PI-RADS category ≥3. The use of LDN-PSAD as an adjunct to the use of prostate specific antigen levels would avoid unnecessary biopsies in patients with the highest PI-RADS category 3. Multi-institutional studies with large population are recommended.


Asunto(s)
Antígeno Prostático Específico , Neoplasias de la Próstata , Humanos , Masculino , Imagen por Resonancia Magnética , Neoplasias de la Próstata/diagnóstico por imagen
5.
J Biol Chem ; 297(4): 101150, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34478711

RESUMEN

Human endometrial stromal cells (ESCs) differentiate into decidual cells by the action of progesterone, which is essential for implantation and maintenance of pregnancy. We previously reported that glucose uptake by human ESCs increases during decidualization and that glucose is indispensable for decidualization. Although glucose transporter 1 (GLUT1) is upregulated during decidualization, it remains unclear whether it is involved in glucose uptake. Here, we attempted to determine the role of GLUT1 during decidualization as well as the factors underlying its upregulation. ESCs were incubated with cAMP to induce decidualization. Knockdown of GLUT1 suppressed cAMP-increased glucose uptake and the expressions of specific markers of decidualization, IGF-binding protein-1 (IGFBP-1), and prolactin (PRL). To investigate the regulation of GLUT1 expression, we focused on CCAAT enhancer-binding protein ß (C/EBPß) and Wilms' tumor 1 (WT1) as the upstream transcription factors regulating GLUT1 expression. Knockdown of either C/EBPß or WT1 suppressed cAMP-increased GLUT1 expression and glucose uptake. cAMP treatment also increased the recruitment of C/EBPß and WT1 to the GLUT1 promoter region. Interestingly, cAMP increased the H3K27 acetylation (H3K27ac) and p300 recruitment in the GLUT1 promoter region. Knockdown of C/EBPß or WT1 inhibited these events, indicating that both C/EBPß and WT1 contribute to the increase of H3K27ac by recruiting p300 to the GLUT1 promoter region during decidualization. These findings indicate that GLUT1 is involved in glucose uptake in ESCs during decidualization, thus facilitating the establishment of pregnancy.


Asunto(s)
Proteína beta Potenciadora de Unión a CCAAT/metabolismo , Decidua/metabolismo , Epigénesis Genética , Transportador de Glucosa de Tipo 1/biosíntesis , Regulación hacia Arriba , Proteínas WT1/metabolismo , Adulto , Proteína beta Potenciadora de Unión a CCAAT/genética , Femenino , Transportador de Glucosa de Tipo 1/genética , Humanos , Persona de Mediana Edad , Células del Estroma , Proteínas WT1/genética
6.
Int J Mol Sci ; 23(12)2022 Jun 16.
Artículo en Inglés | MEDLINE | ID: mdl-35743171

RESUMEN

Melatonin is a promising reagent that can improve assisted reproductive technology (ART) outcomes in infertility patients. However, melatonin is not effective for all infertile patients, and it remains unclear for which patients melatonin would be effective. This study examined the effects of melatonin on ART outcomes and examined its mechanisms. Melatonin increased the fertilization rate in patients whose fertilization rates in the previous cycle were less than 50%, but not in patients whose fertilization rates were more than 50% in the previous cycle. Melatonin increased the blastocyst formation rate in patients whose embryo development rates in the previous cycle were less than 50%, but not in patients whose embryo development rates were more than 50% in the previous cycle. To clarify its mechanisms, transcriptome changes by melatonin treatment in granulosa cells (GCs) of the patients were examined by RNA-sequence. Melatonin treatment altered the transcriptomes of GCs of patients with poor ART outcomes so that they were similar to the transcriptomes of patients with good ART outcomes. The altered genes were associated with the inhibition of cell death and T-cell activity, and the activation of steroidogenesis and angiogenesis. Melatonin treatment was effective for patients with poor fertilization rates and poor embryo development rates in the previous ART cycle. Melatonin alters the GCs transcriptome and, thus, their functions, and this could improve the oocyte quality, leading to good ART outcomes.


Asunto(s)
Melatonina , Blastocisto , Desarrollo Embrionario/genética , Femenino , Fertilización , Fertilización In Vitro , Células de la Granulosa , Humanos , Melatonina/farmacología , Oocitos , Transcriptoma
7.
J Biol Chem ; 295(14): 4673-4683, 2020 04 03.
Artículo en Inglés | MEDLINE | ID: mdl-32098869

RESUMEN

We previously reported that the transcription factor Wilms tumor 1 (WT1) regulates the expression of insulin-like growth factor-binding protein-1 (IGFBP-1) and prolactin (PRL) during decidualization of human endometrial stromal cells (ESCs). However, other roles of WT1 in decidualization remain to be fully clarified. Here, we investigated how WT1 regulates the physiological functions of human ESCs during decidualization. We incubated ESCs isolated from proliferative-phase endometrium with cAMP to induce decidualization, knocked down WT1 with siRNA, and generated three types of treatments (nontreated cells, cAMP-treated cells, and cAMP-treated + WT1-knockdown cells). To identify WT1-regulated genes, we used gene microarrays and compared the transcriptome data obtained among these three treatments. We observed that WT1 up-regulates 121 genes during decidualization, including several genes involved in lipid transport. The WT1 knockdown inhibited lipid accumulation (LA) in the cAMP-induced ESCs. To examine the mechanisms by which WT1 regulates LA, we focused on very low-density lipoprotein receptor (VLDLR), which is involved in lipoprotein uptake. We found that cAMP up-regulates VLDLR and that the WT1 knockdown inhibits it. Results of ChIP assays revealed that cAMP increases the recruitment of WT1 to the promoter region of the VLDLR gene, indicating that WT1 regulates VLDLR expression. Moreover, VLDLR knockdown inhibited cAMP-induced LA, and VLDLR overexpression reverted the suppression of LA caused by the WT1 knockdown. Taken together, our results indicate that WT1 enhances lipid storage by up-regulating VLDLR expression in human ESCs during decidualization.


Asunto(s)
Metabolismo de los Lípidos , Proteínas WT1/metabolismo , Adulto , Células Cultivadas , AMP Cíclico/metabolismo , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Endometrio/citología , Femenino , Regulación de la Expresión Génica , Humanos , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 1 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Persona de Mediana Edad , Regiones Promotoras Genéticas , Unión Proteica , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Receptores de LDL/antagonistas & inhibidores , Receptores de LDL/genética , Receptores de LDL/metabolismo , Células del Estroma/citología , Células del Estroma/metabolismo , Proteínas WT1/antagonistas & inhibidores , Proteínas WT1/genética
8.
BMC Cancer ; 21(1): 476, 2021 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-33926418

RESUMEN

BACKGROUND: The initial therapeutic strategy for hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer is based on the first metastatic site; however, little evidence is available regarding the influence of metastatic distribution patterns of first metastatic sites on prognosis. In this study, we aimed to identify the metastatic distribution patterns of first metastatic sites that significantly correlate with survival after recurrence. METHODS: We performed a retrospective review of records from 271 patients with recurrent metastatic HR+/HER2- breast cancer diagnosed between January 2000 and December 2015. We assessed survival after recurrence according to the metastatic distribution patterns of the first metastatic sites and identified significant prognostic factors among patients with single and multiple metastases. RESULTS: Prognosis was significantly better in patients with a single metastasis than in those with multiple metastases (median overall survival after recurrence: 5.86 years vs. 2.50 years, respectively, p < 0.001). No metastatic organ site with single metastasis was significantly associated with prognostic outcome, although single metastasis with diffuse lesions was an independent risk factor for worse prognosis (HR: 3.641; 95% CI: 1.856-7.141) and more easily progressing to multiple metastases (p = 0.002). Multiple metastases, including liver metastasis (HR: 3.145; 95% CI: 1.802-5.495) or brain metastasis (HR: 3.289; 95% CI: 1.355-7.937), were regarded as significant independent poor prognostic factors; however, multiple metastases not involving liver or brain metastasis were not significantly related to prognosis after recurrence. CONCLUSIONS: Single metastases with diffuse lesions could more easily disseminate systemically and progress to multiple metastases, leading to a poor prognosis similar to multiple metastases. Our findings indicate that the reconsideration of the determinant factors of therapeutic strategies for first recurrence in HR+/HER2- breast cancer may be needed.


Asunto(s)
Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Recurrencia Local de Neoplasia/mortalidad , Receptores de Estrógenos , Receptores de Progesterona , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias Óseas/mortalidad , Neoplasias Óseas/secundario , Neoplasias Encefálicas/mortalidad , Neoplasias Encefálicas/secundario , Neoplasias de la Mama/química , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/secundario , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/secundario , Metástasis Linfática , Persona de Mediana Edad , Recurrencia Local de Neoplasia/química , Neoplasias Pleurales/mortalidad , Neoplasias Pleurales/secundario , Pronóstico , Receptor ErbB-2 , Estudios Retrospectivos
9.
Jpn J Clin Oncol ; 51(2): 205-212, 2021 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-33556170

RESUMEN

PURPOSE: Computed tomography of the abdomen and pelvis is a useful imaging modality for identifying origin and extent of ovarian cancer before primary debulking surgery. However, the International Federation of Gynecology and Obstetrics staging for ovarian cancer is determined based on surgico-pathological findings. The purpose of this study is to determine whether computed tomography staging can be the surrogate for surgico-pathological International Federation of Gynecology and Obstetrics staging in advanced ovarian cancer undergoing neoadjuvant chemotherapy. METHODS: Computed tomography staging was compared with surgico-pathological International Federation of Gynecology and Obstetrics staging in primary debulking surgery arm patients in a randomized controlled trial comparing primary debulking surgery and neoadjuvant chemotherapy (JCOG0602). The cancer of primary debulking surgery arm was identically diagnosed regarding the origin and extent with the cancer of neoadjuvant chemotherapy arm before accrual, using imaging studies (computed tomography and/or magnetic resonance imaging), cytological examination (ascites, pleural effusion or tumor contents fluid) and tumor marker (CA125 > 200 U/mL and CEA < 20 ng/mL). Institutional computed tomography staging was also compared with computed tomography staging by central review. RESULTS: Among 149 primary debulking surgery arm patients, 147 patients who underwent primary debulking surgery immediately were analyzed. Positive predictive values and sensitivity of computed tomography staging for surgical stage III disease (extra-pelvic peritoneal disease and/or retroperitoneal lymph node metastasis) were 99%. Meanwhile, positive predictive values for the presence of small (≤2 cm) extra-pelvic peritoneal disease were low; <20% in omentum. Accuracy of institutional computed tomography staging was comparable with computed tomography staging by central review. CONCLUSIONS: Preoperative computed tomography staging in each institution can be the surrogate for surgico-pathological diagnosis in stage III disease of ovarian cancer patients undergoing neoadjuvant chemotherapy without diagnostic surgery, but reliability of diagnosis of stage IIIB disease is inadequate.Clinical trial registration: UMIN000000523(UMIN-CTR).


Asunto(s)
Neoplasias de las Trompas Uterinas/diagnóstico por imagen , Neoplasias de las Trompas Uterinas/diagnóstico , Oncología Médica , Neoplasias Ováricas/diagnóstico por imagen , Neoplasias Ováricas/diagnóstico , Neoplasias Peritoneales/diagnóstico por imagen , Neoplasias Peritoneales/diagnóstico , Tomografía Computarizada por Rayos X , Adulto , Anciano , Procedimientos Quirúrgicos de Citorreducción , Femenino , Humanos , Japón , Ganglios Linfáticos/patología , Metástasis Linfática/diagnóstico por imagen , Metástasis Linfática/patología , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Ováricas/patología , Neoplasias Ováricas/cirugía , Neoplasias Peritoneales/patología , Neoplasias Peritoneales/cirugía , Reproducibilidad de los Resultados
10.
Int J Mol Sci ; 22(23)2021 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-34884902

RESUMEN

The T-box transcription factor Eomesodermin (Eomes) promotes the expression of interferon-γ (IFN-γ). We recently reported that the small molecule inhibitors, TPCA-1 and IKK-16, which target nuclear factor κB (NF-κB) activation, moderately reduced Eomes-dependent IFN-γ expression in mouse lymphoma BW5147 cells stimulated with phorbol 12-myristate 13-acetate (PMA) and ionomycin (IM). In the present study, we investigated the direct effects of NF-κB on IFN-γ expression in mouse lymphoma EL4 cells and primary effector T cells. Eomes strongly promoted IFN-γ expression and the binding of RelA and NFATc2 to the IFN-γ promoter when EL4 cells were stimulated with PMA and IM. Neither TPCA-1 nor IKK-16 reduced IFN-γ expression; however, they markedly decreased interleukin (IL)-2 expression in Eomes-transfected EL4 cells. Moreover, TPCA-1 markedly inhibited the binding of RelA, but not that of Eomes or NFATc2 to the IFN-γ promoter. In effector CD4+ and CD8+ T cells activated with anti-CD3 and anti-CD28 antibodies, IFN-γ expression induced by PMA and A23187 was not markedly decreased by TPCA-1 or IKK-16 under conditions where IL-2 expression was markedly reduced. Therefore, the present results revealed that NF-κB is dispensable for IFN-γ expression induced by PMA and calcium ionophores in EL4 cells expressing Eomes and primary effector T cells.


Asunto(s)
Ionóforos de Calcio/farmacología , Interferón gamma/genética , FN-kappa B/metabolismo , Bibliotecas de Moléculas Pequeñas/farmacología , Acetato de Tetradecanoilforbol/farmacología , Amidas/farmacología , Animales , Linfocitos T CD4-Positivos/efectos de los fármacos , Linfocitos T CD4-Positivos/metabolismo , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/metabolismo , Línea Celular Tumoral , Femenino , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Interferón gamma/metabolismo , Interleucina-2/metabolismo , Ratones , Piperidinas/farmacología , Cultivo Primario de Células , Regiones Promotoras Genéticas/efectos de los fármacos , Pirrolidinas/farmacología , Proteínas de Dominio T Box/metabolismo , Tiofenos/farmacología
11.
Reprod Med Biol ; 20(3): 299-304, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34262397

RESUMEN

PURPOSE: We investigate the relationships between oocyte developmental capacity and follicular size of its origin in Japanese women: those undergoing conventional IVF (cIVF) and ICSI, respectively. METHODS: A total of 3377 follicles were punctured separately and were classified into three groups (large, medium, and small) by their diameters. A total of 1482 retrieved oocytes were individually cultured and received cIVF or ICSI. The oocytes receiving ICSI were denuded and the number of mature (MII) oocytes was counted. RESULTS: The oocyte retrieval rates and the proportion of MII oocytes were significantly lower in small follicles than in large follicles. Under cIVF, the fertilization rate was significantly lower in oocytes from small follicles than large follicles. Under ICSI, the fertilization rate for MII oocytes was not significantly related to follicular size. Follicular size was not significantly related to the development potential to blastocyst and pregnancy rate for either the cIVF oocytes or the ICSI oocytes. CONCLUSIONS: Although the fertilization rate by cIVF is low in oocytes from small follicles due to the lower proportion of mature oocytes, their development potential is comparable to that of oocytes from larger follicles if they could be fertilized. Under ICSI using mature oocytes, their development potential is not related to follicular size.

12.
Biochem Biophys Res Commun ; 529(2): 243-250, 2020 08 20.
Artículo en Inglés | MEDLINE | ID: mdl-32703418

RESUMEN

Higher consumption of trans fatty acid (TFA) is a risk factor for several inflammatory diseases including inflammatory bowel disease (IBD). However, the detailed mechanisms by which TFA intake affects IBD pathology remain unclear. We demonstrate here that elaidate, a trans-isomer of oleate, enhances interleukin (IL)-1ß production through the activation of NLRP3 inflammasome in mouse bone marrow-derived macrophages (BMDMs). Oleate has no effect on IL-1ß production. Elaidate also induces oxidative stress and activates endoplasmic reticulum stress in BMDMs. The elaidate-induced IL-1ß production is suppressed by co-treatments with antioxidants and a chemical chaperone. Furthermore, we analyze the effects of elaidate administration on intestinal inflammation using 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced colitis model in mice. Increased colonic damage and myeloperoxidase activity after TNBS treatment are elevated by elaidate administration. Also, TNBS treatment induces IL-1ß production in colonic mucosa; elaidate administration enhances the induction. We believe that these data reveal some mechanisms by which the TFA intake is associated with increased risk for IBD.


Asunto(s)
Colitis/metabolismo , Inflamasomas/metabolismo , Macrófagos/patología , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Ácidos Grasos trans/metabolismo , Animales , Células Cultivadas , Colitis/patología , Inflamación/metabolismo , Inflamación/patología , Interleucina-1beta/metabolismo , Intestinos/patología , Macrófagos/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL
15.
J Immunol ; 195(12): 5696-706, 2015 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-26546607

RESUMEN

We investigated whether phagocytosis participates in the protection of insects from viral infection using the natural host-virus interaction between Drosophila melanogaster and Drosophila C virus (DCV). Drosophila S2 cells were induced to undergo apoptotic cell death upon DCV infection. However, UV-inactivated virus was unable to cause apoptosis, indicating the need for productive infection for apoptosis induction. S2 cells became susceptible to phagocytosis by hemocyte-derived l(2)mbn cells after viral infection, and the presence of phagocytes in S2 cell cultures reduced viral proliferation. Phagocytosis depended, in part, on caspase activity in S2 cells, as well as the engulfment receptors Draper and integrin ßν in phagocytes. To validate the in vivo situation, adult flies were abdominally infected with DCV, followed by the analysis of fly death and viral growth. DCV infection killed flies in a dose-responding manner, and the activation of effector caspases was evident, as revealed by the cleavage of a target protein ectopically expressed in flies. Furthermore, hemocytes isolated from infected flies contained DCV-infected cells, and preinjection of latex beads to inhibit the phagocytic activity of hemocytes accelerated fly death after viral infection. Likewise, viral virulence was exaggerated in flies lacking the engulfment receptors, and was accompanied by the augmented proliferation of virus. Finally, phagocytosis of DCV-infected cells in vitro was inhibited by phosphatidylserine-containing liposome, and virus-infected flies died early when a phosphatidylserine-binding protein was ectopically expressed. Collectively, our study demonstrates that the apoptosis-dependent, phosphatidylserine-mediated phagocytosis of virus-infected cells plays an important role in innate immune responses against viral infection in Drosophila.


Asunto(s)
Proteínas de Drosophila/metabolismo , Drosophila melanogaster/inmunología , Hemocitos/fisiología , Virus de Insectos/fisiología , Cadenas beta de Integrinas/metabolismo , Proteínas de la Membrana/metabolismo , Fagocitos/fisiología , Virosis/inmunología , Animales , Apoptosis/efectos de la radiación , Caspasas Efectoras/genética , Caspasas Efectoras/metabolismo , Línea Celular , Proteínas de Drosophila/genética , Drosophila melanogaster/virología , Hemocitos/virología , Inmunidad Innata , Virus de Insectos/patogenicidad , Virus de Insectos/efectos de la radiación , Cadenas beta de Integrinas/genética , Proteínas de la Membrana/genética , Mutación/genética , Fagocitos/virología , Fagocitosis/genética , Fosfatidilserinas/metabolismo , Rayos Ultravioleta , Virulencia
16.
Kyobu Geka ; 70(8): 720-727, 2017 07.
Artículo en Japonés | MEDLINE | ID: mdl-28790297

RESUMEN

Patients with esophageal cancer are often treated with definitive chemoradiotherapy (dCRT). Regardless of arrival at dCRT, the risk of local/regional recurrence during follow-up is significant. Many patient are faced with limited options for therapy once dCRT has failed. Salvage surgery is the only way for complete cure of patients with local/regional recurrent esophageal cancer after dCRT. However, salvage surgery has a significant high risk of fatal complications. We examine our preventive measures to reduce the incidence of postoperative complications after salvage surgery for thoracic esophageal cancer. The points of our preventive measures are them; I. the ingenuity of surgery, II. the securement of blood supply for the respiratory tract, III. standard lymphadenectomy, IV. countermeasures of anastomotic failure, V. countermeasures of dead space, VI. countermeasures of respiratory complications, VII. perioperative managements. Salvage surgery is a reasonable option to treat patients with local/regional recurrence after failed dCRT. Our preventive mesures are effective, therefore, we have to make the further technological developments and the safety of salvage surgery.


Asunto(s)
Carcinoma de Células Escamosas/cirugía , Quimioradioterapia , Neoplasias Esofágicas/cirugía , Recurrencia Local de Neoplasia/cirugía , Complicaciones Posoperatorias/prevención & control , Terapia Recuperativa/efectos adversos , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/terapia , Esofagectomía , Humanos , Estudios Retrospectivos , Insuficiencia del Tratamiento
17.
Gan To Kagaku Ryoho ; 44(12): 1720-1722, 2017 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-29394754

RESUMEN

Prognosis of locally advanced esophageal cancer is poor. The greatest prognostic factor of locally advanced esophageal cancer is a local control. We experienced a case of T4 locally advanced thoracic esophageal cancer who was successfully resected without any combined resection after multimodality therapy. A male in 75-year-old. was diagnosed with type 3 locally advanced upper thoracic esophageal cancer whose metastatic right recurrent laryngeal lymph node invaded into the trachea. Definitive chemoradiation therapy(CRT)was performed, leading to a significant shrinkage of the main tumor, but T4 lesion remained. Next, adding DCF therapy(docetaxel, CDDP and 5-FU), a relief of T4 was finally obtained. Then, salvage surgery with subtotalesophagectomy and retrosternalesophagealreconstruction with gastric tube was performed, resulting in R0 resection without any combined resection. The postoperative course was uneventful, and the patient has been alive without recurrence for 1 year after surgery. In locally advanced cancer, focusing on T4 downstaging, it is significantly important in terms of safety, curativity and organ preservation to perform surgery after a sure sign of T4 relief by multimodality therapy.


Asunto(s)
Neoplasias Esofágicas/terapia , Laringe/cirugía , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Terapia Combinada , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Humanos , Masculino , Estadificación de Neoplasias
18.
Gan To Kagaku Ryoho ; 44(12): 1723-1725, 2017 Nov.
Artículo en Japonés | MEDLINE | ID: mdl-29394755

RESUMEN

The usefulness and safety of imatinibfor neoadjuvant chemotherapy for resectable gastrointestinal stromal tumor(GIST) has not been established. We reported a case of a huge GIST of the stomach that was safely resected following preoperative imatinibtherapy. A 69-year-old man was hospitalized with abdominal fullness which increased rapidly from a month ago. A CT scan showed a huge tumor containing solid and cystic component which was accompanied by an extra-wall nodule. The tumor was strongly suspected to be originated from the stomach and EUS-FNA revealed GIST. We diagnosed GIST of the stomach and initiated preoperative adjuvant chemotherapy with imatinib because there was a risk for the break of tumor capsule and composite resection of the other organs without prior chemotherapy. After the administration of imatinib4 00 mg/day for 6months, the solid component was decreased in size and its' activity by PET-CT had declined, but the size of the cystic component was not changed and the patient's complaint of fullness was not reduced. Then, after a week cessation of imatinib, we performed surgical removal of the tumor with partial gastrectomy without surgical complication during and after the operation. Imatinibwas resumed 2 weeks later postoperatively and 1 year and 8 months has passed since the operation without recurrence. Neoadjuvant chemotherapy with imatinibhas the potential to become an important therapeutic option for the treatment of huge GISTs.


Asunto(s)
Antineoplásicos/uso terapéutico , Tumores del Estroma Gastrointestinal/cirugía , Mesilato de Imatinib/uso terapéutico , Terapia Neoadyuvante , Neoplasias Gástricas/cirugía , Anciano , Gastrectomía , Tumores del Estroma Gastrointestinal/tratamiento farmacológico , Humanos , Masculino , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/patología
19.
Acta Radiol ; 57(3): 378-83, 2016 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-25838450

RESUMEN

BACKGROUND: Tumor volumetry with magnetic resonance imaging (MRI) is very common; however, the accuracy of such measures remains unclear, especially after treatment. PURPOSE: To determine the accuracy of preoperative volume measurements of uterine cervical carcinomas resected with and without neoadjuvant chemotherapy (NAC) on T2-weighted (T2W) and diffusion-weighted (DWI) MRI. MATERIAL AND METHODS: Twenty-nine consecutive patients with surgically confirmed uterine cervical carcinoma were included in this study. MRI scans were performed before preoperative treatment in 17 patients and after two courses of NAC in 12 patients. In all patients, T2W images and DWI were obtained to measure the tumor diameters. The maximum diameter of the surgical specimens was macroscopically measured. The correlation coefficients between the measured tumor size using T2W imaging and DWI and the size measured on the surgical specimens were calculated for all specimens. RESULTS: The correlation coefficient of the three-dimensional (3D) tumor volume measurement using T2W imaging and DWI was 0.97 in the primary surgery group and was 0.96 in the NAC group. The 3D tumor volume measurement using MRI and the measurement of the actual surgical specimen was 0.55 for T2WI and 0.48 for DWI in the primary surgery group and 0.88 for T2WI and 0.95 for DWI in the NAC group. CONCLUSION: T2WI and DWI can provide accurate 3D tumor volume measurements of uterine cervical carcinomas in patients with and without preoperative chemotherapy, suggesting that tumor volumetry using 3 T MRI after uterus-preserving treatment is feasible.


Asunto(s)
Imagen por Resonancia Magnética , Terapia Neoadyuvante , Neoplasias del Cuello Uterino/tratamiento farmacológico , Neoplasias del Cuello Uterino/patología , Cuello del Útero/patología , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Imagenología Tridimensional , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos
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