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BACKGROUND: Schnitzler syndrome is a rare disorder with chronic urticaria, and there is no report summarizing the current status in Japan. METHODS: A nationwide survey of major dermatology departments in Japan was conducted in 2019. We further performed a systematic search of PubMed and Ichushi-Web, using the keywords "Schnitzler syndrome" and "Japan" then contacted the corresponding authors or physicians for further information. RESULTS: Excluding duplicates, a total of 36 clinically diagnosed cases were identified from 1994 through the spring of 2022, with a male to female ratio of 1:1. The median age of onset was 56.5 years. It took 3.3 years from the first symptom, mostly urticaria, to reach the final diagnosis. The current status of 30 cases was ascertained; two patients developed B-cell lymphoma. SchS treatment was generally effective with high doses of corticosteroids, but symptoms sometimes recurred after tapering. Colchicine was administered in 17 cases and was effective in 8, but showed no effect in the others. Tocilizumab, used in six cases, improved laboratory abnormalities and symptoms, but lost its efficacy after several years. Rituximab, used in five cases, was effective in reducing serum IgM levels or lymphoma mass, but not in inflammatory symptoms. Four cases were treated with IL-1 targeting therapy, either anakinra or canakinumab, and achieved complete remission, except one case with diffuse large B-cell lymphoma. CONCLUSIONS: Since Schnitzler syndrome is a rare disease, the continuous collection and long-term follow-up of clinical information is essential for its appropriate treatment and further understanding of its pathophysiology.
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Urticaria Crónica , Síndrome de Schnitzler , Urticaria , Humanos , Masculino , Femenino , Persona de Mediana Edad , Síndrome de Schnitzler/diagnóstico , Síndrome de Schnitzler/tratamiento farmacológico , Urticaria/diagnóstico , Proteína Antagonista del Receptor de Interleucina 1/uso terapéutico , Urticaria Crónica/tratamiento farmacológico , Japón/epidemiologíaRESUMEN
Colorectal cancer (CRC) is a heterogenous disease, and patients have differences in therapeutic response. However, the mechanisms underlying interpatient heterogeneity in the response to chemotherapeutic agents remain to be elucidated, and molecular tumor characteristics are required to select patients for specific therapies. Patient-derived organoids (PDOs) established from CRCs recapitulate various biological characteristics of tumor tissues, including cellular heterogeneity and the response to chemotherapy. Patient-derived organoids established from CRCs show various morphologies, but there are no criteria for defining these morphologies, which hampers the analysis of their biological significance. Here, we developed an artificial intelligence (AI)-based classifier to categorize PDOs based on microscopic images according to their similarity in appearance and classified tubular adenocarcinoma-derived PDOs into six types. Transcriptome analysis identified differential expression of genes related to cell adhesion in some of the morphological types. Genes involved in ribosome biogenesis were also differentially expressed and were most highly expressed in morphological types showing CRC stem cell properties. We identified an RNA polymerase I inhibitor, CX-5641, to be an upstream regulator of these type-specific gene sets. Notably, PDO types with increased expression of genes involved in ribosome biogenesis were resistant to CX-5461 treatment. Taken together, these results uncover the biological significance of the morphology of PDOs and provide novel indicators by which to categorize CRCs. Therefore, the AI-based classifier is a useful tool to support PDO-based cancer research.
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Adenocarcinoma , Antineoplásicos , Neoplasias Colorrectales , Adenocarcinoma/tratamiento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Antineoplásicos/farmacología , Inteligencia Artificial , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Humanos , Organoides/metabolismoRESUMEN
OBJECTIVES: To evaluate the oncologic and obstetric outcomes of cervical conization followed by pelvic lymphadenectomy, which is used as a fertility-sparing procedure, in reproductive-aged patients with early-stage cervical cancer. METHODS: We performed a retrospective study of patients with stage IA1-IB1 cervical cancer who underwent cervical conization followed by pelvic lymphadenectomy from 2011 to 2020 at Kumamoto University Hospital. RESULTS: In total, eight patients underwent conization followed by pelvic lymphadenectomy. The median age of the patients was 33 (range: 28-36) years. Four (50.0%) patients were nulliparous. Seven (87.5%) patients were diagnosed with squamous cell carcinoma (87.5%) and one (12.5%) with adenocarcinoma. Five (62.5%), two (25.0%), and one (12.5%) presented with stage IA1, IA2, and IB1 disease, respectively. Five (62.5%) patients had lymphovascular space invasion (LVSI) based on the assessment of specimens obtained via conization. However, none had lymph node metastasis based on pelvic lymphadenectomy. Regarding long-term oncologic outcomes, recurrence was not observed at a median follow-up of 60 (range: 8-107) months. In addition, obstetric outcomes were consistently favorable in terms of achieving pregnancy, preterm delivery, and live birth. During the study period, two patients who actively attempted to conceive had four pregnancies, resulting in full-term deliveries, and one was on her first trimester of pregnancy. CONCLUSION: Cervical conization combined with pelvic lymphadenectomy represents a feasible conservative management for histologically well-selected patients with early-stage cervical cancer. Furthermore, an optimal histopathological evaluation of conization specimens will contribute to decision-making regarding the use of this fertility-sparing procedure.
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Preservación de la Fertilidad , Neoplasias del Cuello Uterino , Adulto , Conización/métodos , Estudios de Factibilidad , Femenino , Preservación de la Fertilidad/métodos , Humanos , Recién Nacido , Escisión del Ganglio Linfático/métodos , Estadificación de Neoplasias , Embarazo , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patología , Neoplasias del Cuello Uterino/cirugíaRESUMEN
A 44-years-old woman who underwent bilateral mastectomy was treated with chemotherapy after axillary lymph nodes and liver metastases recurrence. She was referred to our hospital for BRCA1/2 germline test and the test revealed BRCA2 pathogenic mutation. Before the administration of olaparib as the fourth-line therapy, liver dysfunction, caused by extensive liver metastasis, was observed. The liver damage improved, and tumor markers decreased immediately as shown in the blood test and CT examination results after 2 months; indicating marked reduction of liver metastasis. In the OlympiAD trial, the patients received olaparib as either the first-, second- or third-line treatment; however, few data on the efficacy of olaparib in the patients, as a late line treatment, were reported. In this article, we report a case of a woman in whom olaparib was used as the fourth-line treatment for metastatic recurrent breast cancer. A high therapeutic effect was obtained and the quality of life has been maintained in her for the past 1 year.
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Neoplasias de la Mama , Adulto , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Mutación de Línea Germinal , Humanos , Mastectomía , Recurrencia Local de Neoplasia , Ftalazinas , Piperazinas , Calidad de VidaRESUMEN
Lateral root formation is an important determinant of root system architecture. In Arabidopsis, lateral roots originate from pericycle cells, which undergo a program of morphogenesis to generate a new lateral root meristem. Despite its importance for root meristem organization, the onset of quiescent center (QC) formation during lateral root morphogenesis remains unclear. Here, we used live 3D confocal imaging to monitor cell organization and identity acquisition during lateral root development. Our dynamic observations revealed an early morphogenesis phase and a late meristem formation phase as proposed in the bi-phasic growth model. Establishment of lateral root QCs coincided with this developmental phase transition. QC precursor cells originated from the outer layer of stage II lateral root primordia, within which the SCARECROW (SCR) transcription factor was specifically expressed. Disrupting SCR function abolished periclinal divisions in this lateral root primordia cell layer and perturbed the formation of QC precursor cells. We conclude that de novo QC establishment in lateral root primordia operates via SCR-mediated formative cell division and coincides with the developmental phase transition.
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Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Raíces de Plantas/metabolismo , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Meristema/genética , Meristema/metabolismo , Raíces de Plantas/genéticaRESUMEN
Gold nanoparticles (AuNPs) have been used as a contrast agent for optical imaging of various single biomolecules. Because AuNPs have high scattering efficiency without photobleaching, biomolecular dynamics have been observed with nanometer localization precision and sub-millisecond time resolution. To understand the working principle of biomolecular motors in greater detail, further improvement of the localization precision and time resolution is necessary. Here, we investigated the lower limit of localization precision achievable with AuNPs and the fundamental law, which determines the localization precision. We first used objective-lens-type total internal reflection dark-field microscopy to obtain a scattering signal from an isolated AuNP. The localization precision was inversely proportional to the square root of the photon number, which is consistent with theoretical estimation. The lower limit of precision for a 40 nm AuNP was â¼0.3 nm with 1 ms time resolution and was restricted by detector saturation. To achieve higher localization precision, we designed and constructed an annular illumination total internal reflection dark-field microscopy system with an axicon lens, which can illuminate the AuNPs at high laser intensity without damaging the objective lens. In addition, we used high image magnification to avoid detector saturation. Consequently, we achieved 1.3 Å localization precision for 40 nm AuNPs and 1.9 Å localization precision for 30 nm AuNPs at 1 ms time resolution. Furthermore, even at 33 µs time resolution, localization precisions at 5.4 Å for 40 nm AuNPs and at 1.7 nm for 30 nm AuNPs were achieved. We then observed motion of head of kinesin-1 labeled with AuNP at microsecond time resolution. Transition cycles of bound/unbound states and tethered diffusion of unbound head during stepping motion on microtubule were clearly captured with higher time resolution or smaller AuNP than those used in previous studies, indicating applicability to single-molecule imaging of biomolecular motors.
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Oro/química , Nanopartículas del Metal , Microscopía , Cinesinas/química , Cinesinas/metabolismo , Movimiento , Factores de TiempoRESUMEN
Trichoderma reesei Cel6A (TrCel6A) is a cellobiohydrolase that hydrolyzes crystalline cellulose into cellobiose. Here we directly observed the reaction cycle (binding, surface movement, and dissociation) of single-molecule intact TrCel6A, isolated catalytic domain (CD), cellulose-binding module (CBM), and CBM and linker (CBM-linker) on crystalline cellulose Iα The CBM-linker showed a binding rate constant almost half that of intact TrCel6A, whereas those of the CD and CBM were only one-tenth of intact TrCel6A. These results indicate that the glycosylated linker region largely contributes to initial binding on crystalline cellulose. After binding, all samples showed slow and fast dissociations, likely caused by the two different bound states due to the heterogeneity of cellulose surface. The CBM showed much higher specificity to the high affinity site than to the low affinity site, whereas the CD did not, suggesting that the CBM leads the CD to the hydrophobic surface of crystalline cellulose. On the cellulose surface, intact molecules showed slow processive movements (8.8 ± 5.5 nm/s) and fast diffusional movements (30-40 nm/s), whereas the CBM-Linker, CD, and a catalytically inactive full-length mutant showed only fast diffusional movements. These results suggest that both direct binding and surface diffusion contribute to searching of the hydrolysable point of cellulose chains. The duration time constant for the processive movement was 7.7 s, and processivity was estimated as 68 ± 42. Our results reveal the role of each domain in the elementary steps of the reaction cycle and provide the first direct evidence of the processive movement of TrCel6A on crystalline cellulose.
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Celulosa 1,4-beta-Celobiosidasa/química , Celulosa/química , Proteínas Fúngicas/química , Trichoderma/enzimología , Celulosa 1,4-beta-Celobiosidasa/genética , Proteínas Fúngicas/genética , Dominios Proteicos , Trichoderma/genéticaRESUMEN
Video-assisted thoracoscopic surgery (VATS) is the standard treatment for spontaneous pneumothorax(SP). Although VATS has decreased the postoperative pain in comparison with conventional thoracotomy, the procedure still often requires sufficient postoperative pain management especially for young patients, and the present study on the postoperative pain management focused on the age difference was designed. Using the numerical rating scale, we compared postoperative pain between the young group(36 patients) and the elderly group (36 patients) selected by propensity score matching in order to adjust for the patients' backgrounds. Although the young group had significantly stronger pain than the elderly group immediately after surgery(4.9±2.5 vs.3.2±2.4, p=0.002), it improved promptly. Moreover, the young group required significantly more frequent continuous infusions of opioids after surgery( p=0.001). In conclusion, it is considered that the postoperative pain management in the pneumothorax surgery should be customized according to the age.
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Dolor Postoperatorio , Neumotórax/cirugía , Cirugía Torácica Asistida por Video/efectos adversos , Adulto , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dimensión del DolorRESUMEN
Cathepsins (CTSs) are lysosomal cysteine proteases that play an important role in the turnover of intracellular proteins and extracellular proteins, such as the degradation of extracellular matrices and the processing of antigenic proteins. A CTS inhibitor, NC-2300, not only suppresses bone erosion by inhibition of cathepsin K (CTSK), but also ameliorates paw swelling at inflamed joints in adjuvant-induced arthritis in rats. It has been demonstrated that the amelioration of joint inflammation by NC-2300 is mediated by the downregulation of cytokine expression in dendritic cells, which are essential for Th17 activation. In this work, we studied the role for CTSs in the pathogenesis of psoriasis-like lesion in K5.Stat3C mice, a mouse model of psoriasis, in which Th17 contributes to lesion development similar to psoriasis. Psoriatic lesions expressed increased levels of Ctsk and Ctss mRNA compared with uninvolved skin and normal control skin. Similarly, the epidermis and dermis in K5.Stat3C mice demonstrated increased CTSK activities, which were sensitive to NC-2300. Topical treatment with NC-2300 significantly ameliorated 12-O-tetradecanoylphorbol-13-acetate-induced psoriasis-like lesions in K5.Stat3C mice, and downregulated the expression of IL-12, IL-23, and Th17 cytokines. In vitro experiments revealed that TLR7 activation of bone marrow-derived myeloid dendritic cells led to increase in IL-23 at mRNA and protein levels, which were downregulated by NC-2300. These results suggest that CTSK plays a role in development of psoriatic lesions through TLR7-dependent Th17 polarization.
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Catepsina K/metabolismo , Dermis/enzimología , Psoriasis/enzimología , Células Th17/enzimología , Receptor Toll-Like 7/metabolismo , Receptor Toll-Like 8/metabolismo , Animales , Médula Ósea/inmunología , Médula Ósea/metabolismo , Médula Ósea/patología , Catepsina K/genética , Catepsina K/inmunología , Dermis/inmunología , Dermis/patología , Regulación hacia Abajo , Epidermis/enzimología , Epidermis/inmunología , Epidermis/patología , Femenino , Humanos , Interleucina-12/genética , Interleucina-12/inmunología , Interleucina-12/metabolismo , Interleucina-23/genética , Interleucina-23/inmunología , Interleucina-23/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Células Mieloides/inmunología , Células Mieloides/metabolismo , Células Mieloides/patología , Psoriasis/genética , Psoriasis/inmunología , Psoriasis/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Células Th17/inmunología , Células Th17/patología , Receptor Toll-Like 7/genética , Receptor Toll-Like 7/inmunología , Receptor Toll-Like 8/genética , Receptor Toll-Like 8/inmunologíaRESUMEN
Understanding the function of rotary molecular motors, such as the rotary ATPases, relies on our ability to visualize the single-molecule rotation. Traditional imaging methods often involve tagging those motors with nanoparticles (NPs) and inferring their rotation from translational motion of NPs. Here, we report an approach using â³two-facedâ³ Janus NPs to directly image the rotation of single V-ATPase from Enterococcus hirae , an ATP-driven rotary ion pump. By employing a 500-nm silica/gold Janus NP, we exploit its asymmetric optical contrast - silica core with a gold cap on one hemisphere - to achieve precise imaging of the unidirectional counter-clockwise rotation of single V-ATPase motors immobilized on surfaces. Despite the added viscous load from the relatively large Janus NP probe, our approach provides accurate torque measurements of single V-ATPase. This study underscores the advantages of Janus NPs over conventional probes, establishing them as powerful tools for single-molecule analysis of rotary molecular motors.
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Pathogenic variants in ABCA12 are important causative genetic defects for autosomal recessive congenital ichthyoses (ARCI), which include congenital ichthyosiform erythroderma (CIE), harlequin ichthyosis, and lamellar ichthyosis. In addition, pathogenic variants in ABCA12 are known to cause a localized nevoid form of CIE due to recessive mosaicism. We previously reported siblings who carried an ABCA12 variant but did not show a "congenital" phenotype. They were considered to have pityriasis rubra pilaris (PRP). Here, we present a further patient with ABCA12 variants whose phenotype was not congenital ichthyosis, in an independent family. Notably, these three patients had geographic unaffected areas. Such areas are not usually found in patients with ARCI who have ABCA12 variants, suggesting mild phenotypes for these patients. Interestingly, the histological features of the ichthyotic lesions in these patients resembled those of PRP. All three patients had homozygous pathogenic missense variants in ABCA12. Our findings expand the phenotypic spectrum of patients with ABCA12 variants.
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Eritrodermia Ictiosiforme Congénita , Ictiosis Lamelar , Ictiosis , Pitiriasis Rubra Pilaris , Humanos , Pitiriasis Rubra Pilaris/genética , Ictiosis Lamelar/genética , Eritrodermia Ictiosiforme Congénita/genética , Eritrodermia Ictiosiforme Congénita/patología , Fenotipo , Mutación , Transportadoras de Casetes de Unión a ATP/genéticaRESUMEN
OBJECTIVE: This study aimed to investigate the prevalence of genitourinary syndrome of menopause (GSM) in Japan using the Japanese translation of the Vulvovaginal Symptoms Questionnaire (VSQ) with online survey. In addition, we examined the relationship between sexual activity and GSM symptoms. METHODS: An online survey on GSM was conducted with 4,134 women aged 40 to 79 years, who were registered in an online survey company. Several questionnaires with Japanese translations of linguistic validity were used in this study. GSM was defined as a condition in women older than 40 years with vulvovaginal symptoms on the VSQ. RESULTS: The percentage of postmenopausal women 40 years and older was 69.6%. The percentage of women with sexual activity was 22%. The prevalence of GSM with vulvovaginal symptoms was 11.6%, and 31.7% in sexually active women. The prevalence of GSM was associated with age and was significantly lower in the 70s age group than in other age groups. Vulvar hurting and dryness were both age-related only in the sexual activity group, with a statistically significantly higher prevalence in the 70s group than in the 40s group. The prevalence of vulvar dryness during sexual activity was significantly lower in the 40s age group. CONCLUSIONS: An online epidemiological survey of GSM was conducted for the first time in Japan using the linguistically validated Japanese translation of the VSQ. The prevalence of GSM with genital or sexual symptoms was 11.6% in Japanese women 40 years and older, and 31.7% in sexually active women.
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Posmenopausia , Enfermedades de la Vulva , Femenino , Humanos , Anciano , Adulto , Vagina/patología , Japón/epidemiología , Enfermedades de la Vulva/patología , Estudios Epidemiológicos , Menopausia , Atrofia/patologíaRESUMEN
PURPOSE: The aim of the study was to evaluate the impact of adding an extensive pelvic peritoneal stripping procedure, termed "wide resection of the pelvic peritoneum," (WRPP) to standard surgery for epithelial ovarian cancer on survival effectiveness and to investigate the role of ovarian cancer stem cells (CSCs) in the pelvic peritoneum. METHODS: A total of 166 patients with ovarian cancer undergoing surgical treatment at Kumamoto University Hospital between 2002 and 2018 were retrospectively analyzed. Eligible patients were divided into three groups based on the surgical approach: standard surgery (SS) group (n = 36), WRPP group (standard surgery plus WRPP, n = 100), and rectosigmoidectomy (RS) group (standard surgery plus RS, n = 30). Survival outcomes were compared between the three groups. CD44 variant 6 (CD44v6) and EpCAM expression, as markers of ovarian CSCs, in peritoneal disseminated tumors were evaluated using immunofluorescence staining. RESULTS: With respect to patients with stage IIIA-IVB ovarian cancer, there were significant differences in overall and progression-free survival between the WRPP and SS groups, as revealed by univariate (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.17-0.69; P = 0.003 and HR, 0.54; 95% CI, 0.31-0.95; P = 0.032, respectively) and multivariate Cox proportional hazards models (HR, 0.35; 95% CI, 0.17-0.70; P = 0.003 and HR, 0.54; 95% CI, 0.31-0.95; P = 0.032, respectively). Further, no significant differences were observed in survival outcomes between the RS group and the SS or WRPP group. Regarding the safety of WRPP, no significant differences in major intraoperative and postoperative complications were found between the three groups. Immunofluorescence analysis revealed a high percentage of CD44v6/EpCAM double-positive ovarian cancer cells in peritoneal disseminated tumors. CONCLUSION: The present study demonstrates that WRPP significantly contributes to improved survival in patients with stage IIIA-IVB ovarian cancer. WRPP could result in eradicating ovarian CSCs and disrupting the CSC niche microenvironment in the pelvic peritoneum.
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Neoplasias Ováricas , Neoplasias Peritoneales , Humanos , Femenino , Carcinoma Epitelial de Ovario/cirugía , Peritoneo/cirugía , Molécula de Adhesión Celular Epitelial , Estudios Retrospectivos , Neoplasias Ováricas/patología , Neoplasias Peritoneales/cirugía , Microambiente TumoralRESUMEN
BACKGROUND/AIM: Breast cancer that is estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor-2 (HER2)-negative is termed triple-negative breast cancer (TNBC). Cytotoxic chemotherapy remains the first choice of treatment against TNBC due to lack of specific therapeutic targets. TNBC is not classified based on therapeutic targets, but recently, the development of targeted therapies - including immune checkpoint inhibitors and poly (adenosine diphosphate-ribose) polymerase inhibitors - has gained attention. This study aimed to examine a novel target-oriented TNBC classification to further facilitate targeted therapy by classifying TNBC based on the breast cancer 1 (BRCA1)-like as well as the protein expression of HER2, programmed death ligand 1 (PD-L1), androgen receptor (AR), cytokeratin 5/6, and epidermal growth factor receptor (EGFR). PATIENTS AND METHODS: We enrolled 17 patients with primary TNBC who did not receive preoperative chemotherapy and underwent surgery at the Kobe University Hospital, Japan, between January 1, 2018, and July 31, 2019. Immunohistochemical staining was performed on tumor specimens, while a BRCAness test was performed using multiplex ligation-dependent probe amplification (MLPA) analysis. A BRCAness score 0.5 or higher was considered BRCA1-like. RESULTS: Tumors were classified as HER2-low (immunohistochemistry score 1+ or 2+ and FISH negative), PD-L1 positive, AR positive, or BRCA1-like. HER2-low, PD-L1 positive, AR positive, and BRCA1-like were detected in 11 (64.7%), 4 (23.5%), 6 (35.3%), and 6 (35.3%) samples. The tumor of only one patient could not be classified into any of these categories. CONCLUSION: Almost all TNBC cases can be classified according to treatable targets.
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Neoplasias de la Mama Triple Negativas , Humanos , Neoplasias de la Mama Triple Negativas/genética , Antígeno B7-H1/genética , Hospitales Universitarios , Inhibidores de Puntos de Control Inmunológico , Japón , Pentosiltransferasa , Poli(ADP-Ribosa) PolimerasasRESUMEN
Activation of the IL-6/Stat3 via IL-6 trans-signaling plays an important role in the pathogenesis of inflammatory bowel disease. Colitis-associated cancer (CAC) is a large bowel cancer and occurs with long-standing inflammatory bowel disease. The role of the IL-6/Stat3 in the development of CAC has not been fully understood. We investigate whether IL-6 trans-signaling contributes to the development of CAC using a mouse colitis-associated premalignant cancer (CApC) model. Chronic colitis (CC) was induced in BALB/c mice using dextran sodium sulfate. CApC was induced by dextran sodium sulfate treatment to CC-affected mice. IL-6 expression was determined by quantitative RT-PCR and immunofluorescence staining in colon. Phospho-Stat3 expression was examined by Western blotting and immunofluorescence analysis. The expression of IL-6 receptors (i.e., the IL-6R alpha-chain and gp130) and tumor necrosis factor-alpha converting enzyme in the colon was examined by laser-capture microdissection and immunofluorescence staining. Soluble IL-6R alpha (sIL-6R alpha) was examined by Western blotting of epithelial cell-depleted colonic tissues. We also investigated whether a soluble gp130-Fc fusion protein could prevent CApC. IL-6 expression was increased in the colon of CC- and CApC-affected mice and was restricted to lamina propria-macrophages. The expression of IL-6R alpha and tumor necrosis factor-alpha converting enzyme was increased in the lamina propria CD11b-macrophages of CC-affected mice. sIL-6R alpha expression was also increased in these tissues. Reduced levels of IL-6R alpha generation were observed in the colonic epithelial cells of CC- and CApC-affected mice and were associated with the increased expression of gp130 and phospho-Stat3. Treatment with soluble gp130Fc significantly reduced the CApC. IL-6 trans-signaling in epithelial cells induced by macrophage-derived IL-6/sIL-6R alpha plays a crucial role in the development of CAC.
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Colon/inmunología , Interleucina-6/fisiología , Mucosa Intestinal/inmunología , Macrófagos/inmunología , Lesiones Precancerosas/inmunología , Receptores de Interleucina-6/fisiología , Transducción de Señal/inmunología , Animales , Enfermedad Crónica , Colon/citología , Neoplasias Colorrectales/inmunología , Neoplasias Colorrectales/patología , Sulfato de Dextran/administración & dosificación , Modelos Animales de Enfermedad , Femenino , Mediadores de Inflamación/administración & dosificación , Mucosa Intestinal/patología , Macrófagos/metabolismo , Macrófagos/patología , Ratones , Ratones Endogámicos BALB C , Membrana Mucosa/inmunología , Membrana Mucosa/patología , Lesiones Precancerosas/patologíaRESUMEN
Periodontal Ehlers-Danlos syndrome (pEDS) is an autosomal-dominant disorder first described by Stewart in 1977 that is characterized by severe gingival recession and periodontitis that triggers premature loss of permanent teeth and alveolar bone absorption. It was recently shown that pEDS is caused by a heterozygous missense mutation in C1R or C1S, which encode complement 1 proteases. Here, we report a familial case of pEDS with a novel heterozygous missense mutation, c.674G>C (p.R225P), in C1R (NM_001733.4). The case exhibited pretibial hyperpigmentation and extended periodontitis but neither skin extensibility nor joint hypermobility, suggesting that this mutation will expand the definition of pEDS.
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Síndrome de Ehlers-Danlos , Inestabilidad de la Articulación , Periodontitis , Síndrome de Ehlers-Danlos/complicaciones , Síndrome de Ehlers-Danlos/diagnóstico , Síndrome de Ehlers-Danlos/genética , Humanos , Inestabilidad de la Articulación/complicaciones , Inestabilidad de la Articulación/genética , Mutación , Mutación Missense , Periodontitis/etiología , PielRESUMEN
A 56-year-old female patient with left breast cancer presented at our hospital. Preoperative CT scan showed an isolated bilateral pectoralis major muscle defect and abnormal muscle originating from the entire sternum and inserting in the lower ribs and rectus sheath. Total mastectomy and axillary lymph node dissection were performed. We believe that this case is unique and that others like it have never been reported. If there is a defect in the pectoralis major muscle, reconstructive surgery with a tissue expander is contraindicated. Therefore, preoperative evaluation of the chest wall musculature on imaging is recommended.
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We have previously shown that xenogeneic stromal cell stimulation of naïve T cells resulted in the generation of a new type of regulatory T (Treg) cell termed HOZOT, which has multifunctional properties and a CD4/CD8 double-positive phenotype. Even after the establishment of HOZOT, stromal cells can function as an antigen-presenting cell (APC) by inducing these cells to produce interleukin (IL)-10. When compared with other stimuli, stromal cells showed an IL-10-producing ability comparable to anti-CD3 antibody (Ab) stimulation, and much greater than dendritic cell (DC) stimulation. Distinct from professional APCs, stromal cells express only major histocompatibility complex (MHC) class I and B7-1 costimulatory molecules, and not MHC class II or other costimulatory molecules, such as ICOSL (CD275), PD-L1 (CD274), PD-L2 (CD273), CD40, OX40L (CD252) and 4-1BBL (CD137L) in the absence of stimulation. Blocking experiments revealed that, in addition to anti-H-2K(d) Ab and anti-human CD8 Ab, anti-mouse B7-1 Ab could effectively block IL-10 production, indicating a key role of the B7-1/CD28 pathway. Using stromal cells expressing different levels of B7-1, IL-10 production correlated with the levels of B7-1 expression. Distinct from ICOSL or PD-L1 expressed on DCs (which are regarded as IL-10-inducing costimulatory molecules), this study showed that B7-1 on stromal cells is a key molecule regulating IL-10 production by multifunctional Treg cells, HOZOT.