RESUMEN
BACKGROUND: Mitotically active cellular fibroma (MACF) of the ovary, characterized by relatively high mitotic activity without severe atypia, represents a relatively new disease entity. MACF is categorized as a benign ovarian tumor. However, due to a limited number of case reports, its clinical and pathological features and optimum management remains largely undetermined. Herein, we report on a rare case of MACF that grew rapidly in size and was diagnosed on detailed pathological examination. CASE PRESENTATION: A 44-year-old Japanese woman, who detected a myoma-like lesion 1-year earlier, was referred to our hospital when the follow-up examination demonstrated that the mass had increased in size. Magnetic resonance imaging revealed a T1 isointense and T2 hyperintense tumor (11 cm in diameter) in the right pelvic cavity. Laparoscopy confirmed the presence of a right ovarian tumor and laparoscopic right adnexectomy was performed. The tumor cells consisted of dense cellular proliferations of spindle fibroblast-like cells without significant cytological atypia. The mitotic activity index was estimated at >15 mitotic figures per 10 high-power fields. Reticulin staining and FOXL2 mutation analysis excluded the possibility of an adult granulosa cell tumor, and the patient was diagnosed with a MACF of the ovary. CONCLUSIONS: To the best of our knowledge, we are the first to report on a case of rapid growth of a MACF of the ovary during follow-up. When an increase in the size of a solid ovarian mass is detected, a MACF should be considered as a differential diagnosis.
Asunto(s)
Proliferación Celular , Fibroma/patología , Mitosis , Neoplasias Ováricas/patología , Adulto , Biomarcadores de Tumor/análisis , Biomarcadores de Tumor/genética , Análisis Mutacional de ADN , Diagnóstico Diferencial , Femenino , Fibroma/química , Fibroma/genética , Fibroma/cirugía , Proteína Forkhead Box L2 , Factores de Transcripción Forkhead/genética , Humanos , Inmunohistoquímica , Laparoscopía , Imagen por Resonancia Magnética , Mutación , Neoplasias Ováricas/química , Neoplasias Ováricas/genética , Neoplasias Ováricas/cirugía , Valor Predictivo de las Pruebas , Reticulina/análisis , Factores de Tiempo , Carga Tumoral , UltrasonografíaRESUMEN
Postnatally, scars occur as a consequence of cutaneous wound healing. Scarless wound healing is highly desired for patients who have undergone surgery or trauma, especially to exposed areas. Based on the properties of mesenchymal stem cells (MSCs) for tissue repair and immunomodulation, we investigated the potential of MSCs for scarless wound healing. MSCs were expanded from umbilical cord blood (UCB-MSCs) and Wharton's jelly (WJ-MSCs) from healthy donors who underwent elective full-term pregnancy caesarean sections. UCB-MSCs expressed lower levels of the pre-inflammatory cytokines IL1A and IL1B, but higher levels of the extracellular matrix (ECM)-degradation enzymes MMP1 and PLAU compared with WJ-MSCs, suggesting that UCB-MSCs were more likely to favor scarless wound healing. However, we failed to find significant benefits for stem cell therapy in improving wound healing and reducing collagen deposition following the direct injection of 1.0 × 10(5) UCB-MSCs and WJ-MSCs into 5 mm full-thickness skin defect sites in nude mice. Interestingly, the implantation of UCB-MSCs tended to increase the expression of MMP2 and PLAU, two proteases involved in degradation of the extracellular matrix in the wound tissues. Based on our data, UCB-MSCs are more likely to be a favorable potential stem cell source for scarless wound healing, although a better experimental model is required for confirmation.
Asunto(s)
Sangre Fetal/citología , Trasplante de Células Madre Mesenquimatosas , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/metabolismo , Gelatina de Wharton/citología , Cicatrización de Heridas , Animales , Biomarcadores , Proliferación Celular , Colágeno/biosíntesis , Citocinas/biosíntesis , Modelos Animales de Enfermedad , Femenino , Fibrosis/genética , Expresión Génica , Inmunofenotipificación , Mediadores de Inflamación/metabolismo , Ratones , Ratones Desnudos , Neovascularización Fisiológica , Fenotipo , Embarazo , Piel/metabolismo , Piel/patologíaRESUMEN
STUDY QUESTION: Is there any combined effect between inflammation and stress reaction on Toll-like receptor 4 (TLR4)-mediated growth of endometriotic cells? SUMMARY ANSWER: A combined effect of local inflammation and stress reaction in the pelvic environment may be involved in TLR4-mediated growth of endometriotic stromal cells. WHAT IS KNOWN ALREADY: In endometriosis, higher endotoxin levels in the menstrual fluid (MF) and peritoneal fluid (PF) and higher tissue concentrations of human heat shock protein 70 (HSP70) in the eutopic and ectopic endometria promote TLR4-mediated growth of endometriotic cells. STUDY DESIGN, SIZE AND DURATION: This is a case-controlled research study with prospective collection and retrospective evaluation of sera, MF, PF and endometrial tissues from 43 women with and 20 women without endometriosis. PARTICIPANTS/MATERIALS, SETTING, METHODS: PF was collected from 43 women with endometriosis and 20 control women during laparoscopy. Sera and endometrial biopsy specimens were collected from a proportion of these women. MF was collected from a separate population of 20 women with endometriosis and 15 control women. HSP70 concentrations in sera, MF, PF and in culture media were measured by ELISA. Gene expression of HSP70 by endometrial cells in response to lipopolysaccharide (LPS) was examined by qRT-PCR. The individual and combined effects of LPS and HSP70 on the secretion of interleukin-6 (IL-6) and tumor necrosis factor α (TNFα) by PF-derived macrophages (M[Symbol: see text]) were examined by ELISA, while their effects on endometrial cell proliferation were examined by bromodeoxyuridine and [(3)H]-thymidine incorporation assay. MAIN RESULTS AND THE ROLE OF CHANCE: Concentrations of HSP70 were maximal in MF, intermediate in PF and the lowest in sera. In MF and PF, HSP70 levels were higher in women with endometriosis than in controls. LPS stimulated gene expression and secretion of HSP70 by eutopic endometrial stromal cells (ESCs) and this effect was abrogated after pretreatment of cells with an anti-TLR4 antibody. This effect was significantly higher for ESCs derived from women with endometriosis than for ESCs from control women. Exogenous treatment with either HSP70 or LPS significantly stimulated the production of IL-6 and TNFα by M[Symbol: see text] and promoted the proliferation of ESCs, and a significant additive effect between LPS and HSP70 was observed. While individual treatment with either polymyxin B, an LPS antagonist, or anti-HSP70 antibody was unable to suppress the combined effects of LPS and HSP70 on cytokine secretion or ESC proliferation, pretreatment of cells with the anti-TLR4 antibody was able to significantly suppress their combined effects. LIMITATIONS, REASONS FOR CAUTIONS: Further studies are needed to examine the mutual role between other secondary inflammatory mediators and endogenous stress proteins in promoting pelvic inflammation and growth of endometriotic stromal cells. WIDER IMPLICATIONS OF THE FINDINGS: Our findings suggest that endotoxin and HSP70 are mutually involved in a stress reaction and in inflammation. A combined effect between local inflammation and a stress reaction in pelvic environment may be involved in TLR4-mediated growth of endometriotic cells. Since endometriosis is a multi-factorial disease, it is difficult to explain uniformly its growth regulation by a single factor. Our findings may provide some new insights in understanding the physiopathology or pathogenesis of endometriosis and may hold new therapeutic potential. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by Grants-in-Aid for Scientific Research (grant no. 16591671 and 18591837) from the Ministry of Education, Sports, Culture, Science and Technology of Japan (to K.N.K.). There is no conflict of interest related to this study. TRIAL REGISTRATION NUMBER: Not applicable.
Asunto(s)
Estrés Fisiológico , Receptor Toll-Like 4/metabolismo , Adulto , Líquido Ascítico/metabolismo , Proliferación Celular , Endometriosis/metabolismo , Endometriosis/patología , Ensayo de Inmunoadsorción Enzimática , Femenino , Proteínas HSP70 de Choque Térmico/sangre , Proteínas HSP70 de Choque Térmico/metabolismo , Proteínas HSP70 de Choque Térmico/farmacología , Humanos , Lipopolisacáridos/farmacología , Productos para la Higiene Menstrual , Células del Estroma/metabolismo , Células del Estroma/patología , Receptor Toll-Like 4/fisiologíaRESUMEN
A 54-year-old female was diagnosed as mixed connective tissue disease (MCTD) complicated with secondary Sjögren's syndrome. Although she had no dyspnea on exertion, the chest X-ray showed cardiomegaly with interstitial pneumonia. The echocardiogram demonstrated asymmetric hypertrophy of the interventricular septum. Diagnosis of hypertrophic obstructive cardiomyopathy (HOCM) was confirmed by left ventriculography and myocardial biopsy. She was treated with prednisolone, resulting in improvement of swollen hand, elevated muscle enzymes and interstitial pneumonia. A rare complication of HOCM with MCTD was described.