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OBJECTIVE@#To explore the clinical characteristics and genetic variant of a patient with desminopathy manifesting with atypical symptoms.@*METHODS@#A patient who was admitted to the Department of Neurology of Jing'an District Central Hospital on February 24, 2021 was selected as the study subject. Clinical data, laboratory tests, muscle pathology, muscle magnetic resonance imaging (MRI) and genetic testing of the patient were retrospectively analyzed.@*RESULTS@#The patient had developed myalgia after lower limb activity, and gradually developed asymmetrical muscle weakness and atrophy of the lower limbs. Cardiac examination revealed atrioventricular block and decreased left ventricular diastolic function. Muscle MRI showed that semitendinosus, sartorius, gracilis, fibula, gastronemius and supinator muscles were selectively involved at the early stage. Muscle biopsy confirmed pathological changes of desmin positive myofibrils. Genetic testing revealed that the patient has harbored a c.1024A>G (p.n342d) missense variant in exon 6 of the DES gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic (PS4_moderate+PM2_supporting+PP3_moderate+PP1).@*CONCLUSION@#Desmin disease has a great clinical heterogeneity. Postexercise myalgia of lower limbs is a rare clinical phenotype. For patients harboring the c.1024A>G (p.n342d) variant of the DES gene, in addition to semitendinosus and fibula, Cardiac involvement is relatively insidious and easy to be ignored in clinic. Timely muscle MRI, muscle biopsy and gene detection will help the early diagnosis of the disease.
Assuntos
Humanos , Mialgia/genética , Desmina/genética , Estudos Retrospectivos , Músculo Esquelético , Extremidade Inferior , MutaçãoRESUMO
Objective: To investigate the clinicopathological characteristics, immunophenotype, molecular genetics and differential diagnoses of fibrocartilaginous lipomas which consist of adipose tissue, fibrocartilage and fibrous elements. Methods: The clinicopathological features, immunohistochemical profiles and molecular profiles in six cases of fibrocartilaginous lipomas diagnosed at Foshan Traditional Chinese Medicine Hospital, Fudan University Shanghai Cancer Center, the Fifth Affiliated Hospital of Zhengzhou University and the Fourth Affiliated Hospital of Harbin Medical University from January 2017 to February 2022 were included. The follow-up information, diagnosis and differential diagnoses were evaluated. Results: There were three males and three females with a median age of 53 years (range 36-69 years) at presentation. Tumors were located in the extremities, the head and neck region and trunk; and presented as painless masses that were located in the subcutaneous tissue or deep soft tissue. Grossly, three cases were well defined with thin capsule, one case was well circumscribed without capsule, two cases were surrounded by some skeletal muscle. The tumors were composed of fatty tissue with intermingled gray-white area. The tumors ranged from 1.50-5.50 cm (mean 2.92 cm). Microscopically, the hallmark of these lesions was the complex admixture of mature adipocytes, fibrocartilage and fibrous element in varying proportions; the fibrocartilage arranged in a nodular, sheet pattern with some adipocytes inside. Tumor cells had a bland appearance without mitotic activity. Immunohistochemical analysis using antibodies to SMA, desmin, S-100, SOX9, HMGA2, RB1, CD34, adipopholin was performed in six cases; the fibrocartilage was positive for S-100 and SOX9, adipocytes were positive for S-100, adipopholin and HMGA2; CD34 was expressed in the fibroblastic cells, while desmin and SMA were negative. Loss of nuclear RB1 expression was not observed. Other genetic abnormalities had not been found yet in four cases. Follow-up information was available in six cases; there was no recurrence in five, and one patient only underwent biopsy of the mass. Conclusions: Fibrocartilaginous lipoma is a benign lipomatous tumor with mature adipocytes, fibrocartilage and fibrous elements. By immunohistochemistry, they show the expression of fat and cartilage markers. No specific molecular genetics changes have been identified so far. Familiarity with its clinicopathological features helps the distinction from its morphologic mimics.
Assuntos
Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Idoso , Desmina/análise , China , Lipoma/patologia , Fibroblastos/patologia , Proteínas S100/análise , Diagnóstico Diferencial , Fibrocartilagem/patologia , Biomarcadores Tumorais/análiseRESUMO
Objective: To explore a simple and feasible method for the isolation and purification of hepatocytes, hepatic stellate cells (HSC), and lymphocytes from mice. Methods: The cell suspension was obtained from male C57bl/6 mice by hepatic perfusion through the portal vein digestion method and then isolated and purified by discontinuous Percoll gradient centrifugation. Trypan blue exclusion was used to determine cell viability. Glycogen staining, cytokeratin 18, and transmission electron microscopy were used to identify hepatic cells. Immunofluorescence was used to detect α-smooth muscle actin combined with desmin in HSCs. Flow cytometry was used to analyze lymphocyte subsets in the liver. Results: After isolation and purification, about 2.7×10(7) hepatocytes, 5.7×10(5) HSCS, and 4.6×106 hepatic mononuclear cells were obtained from the liver of mice with a body weight of about 22g. The cell survival rate in each group was > 95%. Hepatocytes were apparent in glycogen deposited purple-red granules and cytokeratin 18. Electron microscopy showed that there were abundant organelles in hepatocytes and tight junctions between cells. HSC had expressed α-smooth muscle actin and desmin. Flow cytometry showed hepatic mononuclear cells, including lymphocyte subsets such as CD4, CD8, NKs, and NKTs. Conclusion: The hepatic perfusion through the portal vein digestion method can isolate multiple primary cells from the liver of mice at once and has the features of simplicity and efficiency.
Assuntos
Masculino , Camundongos , Animais , Queratina-18 , Actinas , Desmina , Fígado , Hepatócitos , Células Estreladas do FígadoRESUMO
OBJECTIVES@#To analyze the clinicopathological features of maxillofacial granular cell tumors (GCT) with the aid of immunohistochemical staining.@*METHODS@#Seven cases of maxillofacial GCT were retrospectively collated, and the microscopic morphology of maxillofacial GCT was analyzed. The expression of S-100, neuron-specific enolase (NSE), SOX-10, CD68, actin, desmin, and Ki-67 in GCT was detected by immunohistochemical staining. The cases were observed in the follow-ups after clinical treatment.@*RESULTS@#All seven GCT tumors lacked envelopes and were poorly defined. Microscopically, the sizes of the tumor cells were large and appeared with inconspicuous cell membranes, forming a syncytium-like appearance. The cytoplasm was filled with characteristic eosinophilic granules. The immunohistochemical results showed that six cases were NSE-positive, five cases were S-100-positive, seven cases were CD68-positive, five cases were SOX-10-positive, one case was actin-positive, and seven cases were desmin-negative. The Ki-67 index did not exceed 5% in all cases. In the follow-up sessions, none of the six cases presented a recurrence.@*CONCLUSIONS@#Maxillofacial GCT has a characteristic histological structure. Immunohistochemical S-100, CD68, and other indicators can assist in diagnosis, and the prognosis is good after clinical resection.
Assuntos
Humanos , Antígeno Ki-67/metabolismo , Tumor de Células Granulares/cirurgia , Estudos Retrospectivos , Actinas/metabolismo , Desmina/metabolismo , Proteínas S100/metabolismoRESUMO
Objective To explore the effect of microRNA-22-3p (miR-22-3p) regulating the expression of Kruppel-like factor 6 (KLF6) on the cardiomyocyte-like differentiation of bone marrow mesenchymal stem cell (BMSC). Methods Rat BMSC was isolated and cultured,and the third-generation BMSC was divided into a control group,a 5-azacytidine(5-AZA)group,a mimics-NC group,a miR-22-3p mimics group,a miR-22-3p mimics+pcDNA group,and a miR-22-3p mimics+pcDNA-KLF6 group.Real-time fluorescent quantitative PCR (qRT-PCR) was carried out to determine the expression of miR-22-3p and KLF6 in cells.Immunofluorescence staining was employed to detect the expression of Desmin,cardiac troponin T (cTnT),and connexin 43 (Cx43).Western blotting was employed to determine the protein levels of cTnT,Cx43,Desmin,and KLF6,and flow cytometry to detect the apoptosis of BMSC.The targeting relationship between miR-22-3p and KLF6 was analyzed by dual luciferase reporter gene assay. Results Compared with the control group,5-AZA up-regulated the expression of miR-22-3p (q=7.971,P<0.001),Desmin (q=7.876,P<0.001),cTnT (q=10.272,P<0.001),and Cx43 (q=6.256,P<0.001),increased the apoptosis rate of BMSC (q=12.708,P<0.001),and down-regulated the mRNA (q=20.850,P<0.001) and protein (q=11.080,P<0.001) levels of KLF6.Compared with the 5-AZA group and the mimics-NC group,miR-22-3p mimics up-regulated the expression of miR-22-3p (q=3.591,P<0.001;q=11.650,P<0.001),Desmin (q=5.975,P<0.001;q=13.579,P<0.001),cTnT (q=7.133,P<0.001;q=17.548,P<0.001),and Cx43 (q=4.571,P=0.037;q=11.068,P<0.001),and down-regulated the mRNA (q=7.384,P<0.001;q=28.234,P<0.001) and protein (q=4.594,P=0.036;q=15.945,P<0.001) levels of KLF6.The apoptosis rate of miR-22-3p mimics group was lower than that of 5-AZA group (q=8.216,P<0.001).Compared with the miR-22-3p mimics+pcDNA group,miR-22-3p mimics+pcDNA-KLF6 up-regulated the mRNA(q=23.891,P<0.001) and protein(q=13.378,P<0.001)levels of KLF6,down-regulated the expression of Desmin (q=9.505,P<0.001),cTnT (q=10.985,P<0.001),and Cx43 (q=8.301,P<0.001),and increased the apoptosis rate (q=4.713,P=0.029).The dual luciferase reporter gene experiment demonstrated that KLF6 was a potential target gene of miR-22-3p. Conclusion MiR-22-3p promotes cardiomyocyte-like differentiation of BMSC by inhibiting the expression of KLF6.
Assuntos
Animais , Ratos , Miócitos Cardíacos , Fator 6 Semelhante a Kruppel , Conexina 43 , Desmina , Diferenciação Celular , Azacitidina/farmacologia , Células-Tronco Mesenquimais , RNA Mensageiro , MicroRNAsRESUMO
OBJECTIVE@#Physical exercise, a common non-drug intervention, is an important strategy in cancer treatment, including hepatocellular carcinoma (HCC). However, the mechanism remains largely unknown. Due to the importance of hypoxia and cancer stemness in the development of HCC, the present study investigated whether the anti-HCC effect of physical exercise is related to its suppression on hypoxia and cancer stemness.@*METHODS@#A physical exercise intervention of swimming (30 min/d, 5 d/week, for 4 weeks) was administered to BALB/c nude mice bearing subcutaneous human HCC tumor. The anti-HCC effect of swimming was assessed in vivo by tumor weight monitoring, hematoxylin and eosin (HE) staining, and immunohistochemistry (IHC) detection of proliferating cell nuclear antigen (PCNA) and Ki67. The expression of stemness transcription factors, including Nanog homeobox (NANOG), octamer-binding transcription factor 4 (OCT-4), v-Myc avian myelocytomatosis viral oncogene homolog (C-MYC) and hypoxia-inducible factor-1α (HIF-1α), was detected using real-time reverse transcription polymerase chain reaction. A hypoxia probe was used to explore the intratumoral hypoxia status. Western blot was used to detect the expression of HIF-1α and proteins related to protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling pathway. The IHC analysis of platelet endothelial cell adhesion molecule-1 (CD31), and the immunofluorescence co-location of CD31 and desmin were used to analyze tumor blood perfusion. SMMC-7721 cells were treated with nude mice serum. The inhibition effect on cancer stemness in vitro was detected using suspension sphere experiments and the expression of stemness transcription factors. The hypoxia status was inferred by measuring the protein and mRNA levels of HIF-1α. Further, the expression of proteins related to Akt/GSK-3β/β-catenin signaling pathway was detected.@*RESULTS@#Swimming significantly reduced the body weight and tumor weight in nude mice bearing HCC tumor. HE staining and IHC results showed a lower necrotic area ratio as well as fewer PCNA or Ki67 positive cells in mice receiving the swimming intervention. Swimming potently alleviated the intratumoral hypoxia, attenuated the cancer stemness, and inhibited the Akt/GSK-3β/β-catenin signaling pathway. Additionally, the desmin+/CD31+ ratio, rather than the number of CD31+ vessels, was significantly increased in swimming-treated mice. In vitro experiments showed that treating cells with the serum from the swimming intervention mice significantly reduced the formation of SMMC-7721 cell suspension sphere, as well as the mRNA expression level of stemness transcription factors. Consistent with the in vivo results, HIF-1α and Akt/GSK-3β/β-catenin signaling pathway were also inhibited in cells treated with serum from swimming group.@*CONCLUSION@#Swimming alleviated hypoxia and attenuated cancer stemness in HCC, through suppression of the Akt/GSK-3β/β-catenin signaling pathway. The alleviation of intratumoral hypoxia was related to the increase in blood perfusion in the tumor. Please cite this article as: Xiao CL, Zhong ZP, Lü C, Guo BJ, Chen JJ, Zhao T, Yin ZF, Li B. Physical exercise suppresses hepatocellular carcinoma progression by alleviating hypoxia and attenuating cancer stemness through the Akt/GSK-3β/β-catenin pathway. J Integr Med. 2023; 21(2): 184-193.
Assuntos
Humanos , Animais , Camundongos , Carcinoma Hepatocelular/tratamento farmacológico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Antígeno Nuclear de Célula em Proliferação/uso terapêutico , Camundongos Nus , Glicogênio Sintase Quinase 3 beta/genética , beta Catenina/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Desmina/uso terapêutico , Antígeno Ki-67 , Linhagem Celular Tumoral , Hipóxia , RNA Mensageiro/uso terapêutico , Proliferação de CélulasRESUMO
El histiocitoma fibroso maligno (MFH) es el tumor de tejido blando más común en adultos. Generalmente se considera que surge de las células mesenquimales primitivas que muestran diferenciación histiocítica y fibroblástica parcial. Las observaciones inmunohistoquímicas sugieren que la expresión de marcadores del músculo liso en el llamado MFH es el resultado de la diferenciación miofibroblástica. El presente estudio tiene como objetivo correlacionarse entre el subtipo histipatológico y los parámetros clínicos, calificar los casos de MFH dependiendo de los criterios histopatológicos para la clasificación, y examinar los casos inmunohistoquímicamente para la diferenciación miofibroblástica utilizando marcadores musculares lisos en casos de MFH como una ayuda para un diagnóstico preciso para un diagnóstico preciso. . Este estudio incluye 26 muestras de tejidos blandos diagnosticados como MFH recolectados de laboratorios histopatológicos privados y gubernamentales en Basrah durante el período de enero de 2000 a octubre de 2005. 4 casos adicionales (un leiomioma, dos fibromas y un fibrosarcoma se tomaron como control positivo y negativo. Los casos de MFH (77%) estaban en el grupo de edad de 45 a 60 años. La edad media fue de 53.5 años con una relación hombre / mujer de 1.3: 1. Diecinueve casos (73%) se ubicaron en las extremidades principalmente en las extremidades inferiores. Diecisiete años. Los casos (65.4%) fueron primarios. Veintidós (84.8%) eran de subtipo pleomórfico, dos eran mixoides y 2 eran inflamatorios. Todos los casos recurrentes se consideraban como el Grado III, de los diecisiete casos principales eran de grado III, por lo que veinte y veinte Tres casos (88.5%) fueron de grado III, los 3 casos restantes fueron de grado II. No se registró tumor de grado I. La mayoría de los casos de subtipo pleomórficos (95.5%) fueron de grado III. Ambos casos de subtipo mixoide fueron de grado Ii. Desmin expr Se encontró la en 3 casos (11.5%), ninguno para la actina del músculo liso o la proteína S-100. No hubo correlación entre la expresión de desmin y el sitio tumoral, subtipo o grado, así como, con la edad y el sexo de los pacientes. Se encontró una fuerte asociación entre la expresión de desmin y los tumores recurrentes del 33,3%
Malignant fibrous histiocytoma (MFH) is the most common soft tissue tumor in adult. It is generally regarded as arising from primitive mesenchymal cells that show partial histiocytic and fibroblastic differentiation. Immunohistochemical observations suggest that the expression of smooth muscle markers in the so called MFH is a result of myofibroblastic differentiation. The present study is aimed to correlate between histipathological subtype and clinical parameters, to grade the MFH cases depending on the histopathological criteria for grading, and to examine the cases immunohistochemically for myofibroblastic differentiation using smooth muscle markers in cases of MFH as an aid for accurate diagnosis. This study including 26 soft tissue specimens diagnosed as MFH collected from private and governmental histopathological laboratories in Basrah during the period from January 2000 to October 2005. Additional 4 cases (one leiomyoma, two fibromas and one fibrosarcoma were taken as control positive and negative. Twenty cases of MFH (77%) were in the age group 45-60 years. The mean age was 53.5 year with male to female ratio of 1.3: 1. Nineteen cases (73%) were located in the extremities mainly the lower limbs. Seventeen cases (65.4%) were primary. Twenty two (84.8%) were of pleomorphic subtype, two were myxoid and 2 were inflammatory. All the recurrent cases were regarded as grade III, from the seventeen primary cases fourteen were of grade III, so twenty three cases (88.5%) were of grade III, the remaining 3 cases were of grade II. No grade I tumor was recorded. The majority of pleomorphic subtype cases (95.5%) were of grade III. Both cases of myxoid subtype were of grade II. Desmin expression was found in only 3 cases (11.5%), none for smooth muscle actin or S-100 protein. There was no correlation between desmin expression and tumor site, subtype or grade, as well as, with age and sex of the patients. A strong association between desmin expression and recurrent tumors 33.3% was found.
Assuntos
Humanos , Pessoa de Meia-Idade , Desmina , Histiocitoma Fibroso Maligno/imunologia , Músculo Liso/patologiaRESUMO
SUMMARY: The aim of this study was to evaluate the effects of stretching and therapeutic ultrasound (TUS) on desmin and laminin contents of rat muscle after contusion. Male Wistar rats (n = 35, 8-9 weeks of age, 271 ± 14g body weight) were divided into five groups: Control group (CG) (n= 03); Injured group (IG) (n= 8); Injured + ultrasound group (IUSG) (n= 8); Injured+stretching group (ISG) (n= 8); Injured +ultrasound + stretching group (IUSSG) (n= 8). The application of ultrasound started 72 hours after the contusion, using the 50 % pulsed mode, 0.5 W/cm2, 5 min, once a day, for five consecutive days. Passive manual stretching was started on the tenth day after injury, with four repetitions of 30 s each and 30 s rest between repetitions, once a day, five times per week, for a total of ten applications. After 22 days, the rats were euthanazied and the gastrocnemius of both limbs removed for desmin and laminin immunohistochemistry morphometric measurement. Analysis was conducted using ANOVA one way post-hoc Tukey to parametric data and Kruskall-Wallis for non-parametric data. The IUSSG animals showed a larger area of desmin than ISG (p<0.05). It was found a decrease in laminin comparing IUSG to IG. However, laminin area was higher in ISG than all groups (p<0.05). UST isolated or in combination with stretching influenced gastrocnemius regeneration in different manners. While stretching applied isolated enhanced gastrocnemius regeneration noticed by the increase in laminin area, in combination with TUS strengthened the muscle healing rising desmin area.
RESUMEN: El objetivo de este estudio fue evaluar los efectos del estiramiento y la ecografía en los contenidos de desmina y laminina del músculo de rata después de la lesión. Ratas Wistar macho (n = 35, 8-9 semanas de edad, 271 ± 14 g de peso corporal) se dividieron en cinco grupos: grupo de control (CG) (n = 03); Grupo lesionado (GL) (n = 8); Lesionado + grupo de ultrasonido (LGU) (n= 8); Lesionado + grupo de estiramiento (LGE) (n = 8); Lesionado + ultrasonido + grupo de estiramiento (LUGE) (n = 8). La aplicación de ultrasonido comenzó 72 horas después de la lesión, usando el modo pulsado al 50 %, 0,5W / cm2, 5 min, una vez al día, durante cinco días consecutivos. El estiramiento manual pasivo se inició el décimo día después de la lesión, con cuatro repeticiones de 30 seg cada una y 30 seg de descanso entre repeticiones, una vez al día, cinco veces por semana, para un total de diez aplicaciones. Las ratas fueron sacrificadas después de 22 días, y se extrajo el músculo gastrocnemio de ambos miembros para la medición morfométrica de desmina y laminina a través de inmunohistoquímica. El análisis se realizó utilizando ANOVA unidireccional Tukey post-hoc para datos paramétricos y Kruskall-Wallis para datos no paramétricos. Los animales LUGE mostraron un área mayor de desmina que LGE (p <0,05). Se encontró una disminución en la laminina comparando LGU con GL. Sin embargo, el área de laminina fue mayor en LGE que en todos los grupos (p <0,05). El tratamiento con ultrasonido aislado o en combinación con estiramiento influyó en la regeneración del músculo gastrocnemio de diferentes maneras. Si bien el estiramiento aplicado, en combinación con tratamiento de ultrasonido, fortaleció el área de desmina, la regeneración del músculo gastrocnemio mejoró por el aumento en el área de laminina aumentando la curación muscular.
Assuntos
Animais , Masculino , Ratos , Terapia por Ultrassom/métodos , Músculo Esquelético/patologia , Contusões/terapia , Exercícios de Alongamento Muscular/métodos , Imuno-Histoquímica , Análise de Variância , Laminina/análise , Ratos Wistar , Músculo Esquelético/lesões , Desmina/análiseRESUMO
Duodenal leiomyosarcoma is a rare condition with a poor prognosis. Early diagnosis of duodenal leiomyosarcoma is challenging because it presents with nonspecific symptoms and endoscopic biopsies usually do not enable a definitive diagnosis. Duodenal leiomyosarcomas are diagnosed on the basis of the histopathological identification of a mesenchymal lesion composed of malignant tumor cells that on immunohistochemical examination is positive for smooth muscle actin and desmin. We report the case of a 38-year-old man who presented with gastrointestinal bleeding and obstruction who was diagnosed with duodenal leiomyosarcoma after surgical resection.
Assuntos
Adulto , Humanos , Actinas , Biópsia , Desmina , Diagnóstico , Obstrução Duodenal , Diagnóstico Precoce , Hemorragia Gastrointestinal , Hemorragia , Leiomiossarcoma , Músculo Liso , PrognósticoRESUMO
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Cicatriz , Colágeno Tipo I , Colágeno , Contratura , Desmina , Regulação para Baixo , Matriz Extracelular , Fibroblastos , Fibronectinas , Fibrose , Folistatina , Terapia Genética , Imuno-Histoquímica , Miofibroblastos , Inibidor 1 de Ativador de Plasminogênio , RNA Mensageiro , Traumatismos dos Tendões , Tendões , Inibidor Tecidual de Metaloproteinase-1RESUMO
Myoepithelioma was recognized as a histological distinct entity by the World Health Organization (WHO) in 1991. Myoepithelial cells are believed to be of ectodermal origin. In salivary glands, the myoepithelial cells that surround the intercalated ducts are spindled, which is in contrast to the large stellate ones that envelop the acini. Myoepithelioma is a benign salivary gland tumor that consists entirely of myoepithelial cells. A 53-year-old man presented with a 1-year history of a painless mass originating from the right parotid gland. The mass grew rapidly reaching a size of approximately 6 cm. The patient had no facial paralysis. The authors performed right parotidectomy. Immunohistochemistry study of this tumor showed that it was positive for vimentin, positive for S-100, focally positive for pancytokeratin, and focally positive for p63 and that it had a Ki-67 labeling index (below 10%). Additionally, the tumor was negative for epithelial membrane antigen, negative for actin, negative for desmin, negative for CD34 and negative for anaplastic lymphoma kinase. The authors present a case of benign spindle cell myoepithelioma of the parotid gland in a 53-year-old man diagnosed after immunohistochemistry study, describing its importance, along with a brief review of the literature.
Assuntos
Humanos , Pessoa de Meia-Idade , Actinas , Desmina , Ectoderma , Paralisia Facial , Imuno-Histoquímica , Linfoma , Mucina-1 , Mioepitelioma , Glândula Parótida , Neoplasias Parotídeas , Fosfotransferases , Glândulas Salivares , Vimentina , Organização Mundial da SaúdeRESUMO
Leiomyosarcoma of the bladder is a very rare tumor and it has been reported in less than 200 cases in the literature which represent 0.1% of all nonurothelial bladder tumors. We experienced a case of sarcoma of bladder that protruding into the urinary bladder in 51-year-old woman. She underwent mass excision with enucleation for the bladder function preservation. Pathologically, the mass consisted of high grade leiomyosarcoma. In immunohistochemical study, tumor showed positive reactions for smooth muscle actin and desmin. After mass excision, follow-up radiation treatment is ongoing. Herein, we present the case of a high-grade leiomyosarcoma with literature review.
Assuntos
Feminino , Humanos , Pessoa de Meia-Idade , Actinas , Desmina , Seguimentos , Leiomiossarcoma , Músculo Liso , Sarcoma , Neoplasias da Bexiga Urinária , Bexiga UrináriaRESUMO
BACKGROUND: Primary breast sarcoma (PBS) is rare, comprising approximately 1% of breast malignancies. Rhabdomyosarcoma (RMS) accounts for an extremely small proportion of PBSs, often leading to delayed histologic confirmation. METHODS: Upon reviewing Asan Medical Center’s pathology database between 2000 and 2018, 41 PBS cases were retrieved, including three cases of primary RMS of the breast. Their clinicopathological features were analyzed, and the literature related to PBS and primary RMS of the breast was reviewed. RESULTS: We identified three primary breast RMS cases from our institution database, comprising 7.3% of PBS: one case each of spindle cell/sclerosing RMS (ssRMS), alveolar RMS (aRMS), and embryonal RMS (eRMS). All cases involved adolescents or young adults (14, 16, and 25 years, respectively) who underwent mastectomy or radiotherapy and were confirmed using immunohistochemical testing for myogenin, desmin, and myogenic differentiation. The ssRMS patient experienced recurrence at the operation site 4 months post-surgery despite undergoing concurrent chemoradiotherapy. The aRMS patient had multiple metastases at diagnosis and showed FAX3-FOXO1 fusion transcripts; she died 22 months after the diagnosis. The eRMS patient had enlarged axillary lymph nodes; post-radiotherapy, the lesion recurred as multiple metastases to the bone and lung. She died 18 months post-diagnosis. CONCLUSIONS: Our experience on RMS cases suggests that spindle cell or small round cell malignancy in breasts of young female should raise suspicion for the possibility of primary or secondary RMS. To our knowledge, this is the second report of primary breast ssRMS and it may help clinicians who encounter this rare disease in the future.
Assuntos
Adolescente , Feminino , Humanos , Adulto Jovem , Braço , Mama , Quimiorradioterapia , Desmina , Diagnóstico , Pulmão , Linfonodos , Mastectomia , Miogenina , Metástase Neoplásica , Patologia , Radioterapia , Doenças Raras , Recidiva , Rabdomiossarcoma , SarcomaRESUMO
BACKGROUND@#Desminopathy, a hereditary myofibrillar myopathy, mainly results from the desmin gene (DES) mutations. Desminopathy involves various phenotypes, mainly including different cardiomyopathies, skeletal myopathy, and arrhythmia. Combined with genotype, it helps us precisely diagnose and treat for desminopathy.@*METHODS@#Sanger sequencing was used to characterize DES variation, and then a minigene assay was used to verify the effect of splice-site mutation on pre-mRNA splicing. Phenotypes were analyzed based on clinical characteristics associated with desminopathy.@*RESULTS@#A splicing mutation (c.735+1G>T) in DES was detected in the proband. A minigene assay revealed skipping of the whole exon 3 and transcription of abnormal pre-mRNA lacking 32 codons. Another affected family member who carried the identical mutation, was identified with a novel phenotype of desminopathy, non-compaction of ventricular myocardium. There were 2 different phenotypes varied in cardiomyopathy and skeletal myopathy among the 2 patients, but no significant correlation between genotype and phenotype was identified.@*CONCLUSIONS@#We reported a novel phenotype with a splicing mutation in DES, enlarging the spectrum of phenotype in desminopathy. Molecular studies of desminopathy should promote our understanding of its pathogenesis and provide a precise molecular diagnosis of this disorder, facilitating clinical prevention and treatment at an early stage.
Assuntos
Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Povo Asiático , Cardiomiopatias , Genética , Patologia , Desmina , Genética , Eletrocardiografia , Genótipo , Distrofias Musculares , Genética , Patologia , Mutação , Genética , Linhagem , FenótipoRESUMO
BACKGROUND: Breast cancer treatment with selective estrogen receptor modulators (SERMs) increases the incidence of uterine malignant mixed Müllerian tumors (uMMMTs). We examine clinicopathologic characteristics and prognosis of SERM-associated uMMMTs (S-uMMMTs) and discuss possible pathogenetic mechanisms. METHODS: Among 28,104 patients with breast cancer, clinicopathologic features and incidence of uMMMT were compared between patients who underwent SERM treatment and those who did not. Of 92 uMMMT cases that occurred during the same period, incidence, dose, and duration of SERM treatment, as well as overall survival rate, were compared for patients with breast cancer who underwent SERM treatment and those who did not (S-uMMMT vs NS-uMMMT) and for patients without breast cancer (de novo-uMMMT). Histopathological findings and immunophenotypes for myogenin, desmin, p53, WT-1, estrogen receptor (ER) α, ERβ, progesterone receptor, and GATA-3 were compared between S-uMMMT and de novo-uMMMT. RESULTS: The incidence of S-uMMMT was significantly higher than that of NS-uMMMT (6.35-fold). All patients with SERM were postmenopausal and received daily 20–40 mg SERM. Cumulative SERM dose ranged from 21.9 to 73.0 g (mean, 46.0) over 39–192 months (mean, 107). Clinicopathologic features, such as International Federation of Gynecology and Obstetrics stage and overall survival, were not significantly different between patients with S-uMMMT and NS-uMMMT or between patients with S-uMMMT and de novo-uMMMT. All 11 S-uMMMT cases available for immunostaining exhibited strong overexpression/null expression of p53 protein and significantly increased ERβ expression in carcinomatous and sarcomatous components. CONCLUSIONS: SERM therapy seemingly increases risk of S-uMMMT development; however, clinicopathologic features were similar in all uMMMTs from different backgrounds. p53 mutation and increased ERβ expression might be involved in the etiology of S-uMMMT.
Assuntos
Humanos , Neoplasias da Mama , Mama , Desmina , Estrogênios , Ginecologia , Incidência , Miogenina , Obstetrícia , Prognóstico , Receptores de Progesterona , Moduladores Seletivos de Receptor Estrogênico , Taxa de Sobrevida , TamoxifenoRESUMO
PURPOSE: Liver fibrosis is a major cause of morbidity and mortality and the outcome of various chronic liver diseases. Activation of hepatic stellate cells (HSCs) is the key event in liver fibrosis. Studies have confirmed that miR-140-3p plays a potential regulatory effect on HSC activation. However, whether miR-140-3p mediates the liver fibrosis remains unknown. MATERIALS AND METHODS: Expression of miR-140-3p was detected by real-time quantitative PCR (qPCR). Cell proliferation was measured by MTT, while cell apoptosis rate was determined via flow cytometry. Western blot assay was used to detect the expression of cleaved PARP. The fibrogenic effect was evaluated by expression of α-smooth muscle actin and desmin. Functional experiments were performed in transforming growth factor β1 (TGF-β1)-induced HSC-T6 cells with transfection of anti-miR-140-3p and/or siPTEN. Target binding between miR-140-3p and PTEN was predicted by the TargetScan database and identified using luciferase reporter assay and RNA immunoprecipitation. RESULTS: TGF-β1 induced the activation of HSC-T6 cells, and miR-140-3p expression varied according to HSC-T6 cell activation status. Knockdown of miR-140-3p reduced cell proliferation and the expressions of α-SMA and desmin, as well as increased apoptosis, in TGF-β1-induced HSC-T6 cells, which could be blocked by PTEN silencing. Additionally, inactivation of the AKT/mTOR signaling pathway stimulated by miR-140-3p knockdown was abolished when silencing PTEN expression. PTEN was negatively regulated by miR-140-3p via direct binding in HSC-T6 cells. CONCLUSION: miR-140-3p is an important mediator in HSC-T6 cell activation, and miR-140-3p knockdown suppresses cell proliferation and fibrogenesis in TGF-β1-induced HSC-T6 cells, indicating that miR-140-3p may be a potential novel molecular target for liver fibrosis.
Assuntos
Actinas , Apoptose , Western Blotting , Proliferação de Células , Desmina , Citometria de Fluxo , Células Estreladas do Fígado , Imunoprecipitação , Cirrose Hepática , Hepatopatias , Luciferases , Mortalidade , Reação em Cadeia da Polimerase , RNA , Transfecção , Fatores de Crescimento TransformadoresRESUMO
Knowing the ultrastructure of skeletal muscle is critical to understand how it works under normal situation and the disorders caused by extreme or pathological conditions. Sarcomere is the basic structural unit of striated muscle tissue. An important element of sarcomere architecture are the intermediate filaments, including the desmin protein. Desmin protein contributes to maintenance of cell integrity, efficient transmission of force and mechanochemical signaling within the myocyte. Because of this, desmin protein has constantly been a focus of research that investigates its alterations associated to damage and muscle atrophy under different conditions. The purpose of the following literature review is to describe the basic concepts of muscle ultrastructure, emphasizing the desmin protein role under conditions of muscle disuse atrophy and aging.
Conocer la ultraestructura del músculo esquelético es crítico para entender cómo trabaja bajo situaciones normales y en desórdenes causados por condiciones extremas o patológicas. La sarcómera es la unidad de estructura básica del tejido muscular estriado. Elementos importantes en la arquitectura de la sarcómera son los filamentos intermedios, incluyendo la proteína desmina. La proteína desmina contribuye en mantener la integridad celular, la transmisión eficiente de fuerza y la señalización mecanoquímica dentro del miocito. Debido a lo anterior, la proteína desmina ha sido constante foco de investigación en trabajos que estudian sus alteraciones asociadas a daño y atrofia muscular bajo diferentes condiciones. El propósito de la siguiente revisión de la literatura es describir los conceptos básicos de la ultraestructura muscular, enfatizando en el rol de la proteína desmina bajo condiciones de atrofia muscular por desuso y envejecimiento.
Assuntos
Humanos , Animais , Sarcômeros/ultraestrutura , Envelhecimento , Músculo Esquelético/ultraestrutura , Desmina/ultraestrutura , Filamentos Intermediários/ultraestruturaRESUMO
A mammary-type myofibroblastoma is a rare benign mesenchymal neoplasm composed of spindle cells initially described to occur in the breast. However, they also arise at extra-mammary sites including the inguinal area, breast, chest wall/axilla, trunk, upper and lower extremities, and head and neck regions. In particular, mammary-type myofibroblastoma of the head and neck are extremely rare and may occur at any age. Immunohistochemically, it is typically CD34 and desmin positive. Currently, complete excision is considered as the first line treatment and recurrence of the tumor is rare. We experienced a 41-year-old man who visited with 1 cm sized firm mass of the tongue. The mass was resected and tissue biopsy revealed a diagnosis of mammary-type myofibroblastoma. Herein we report a rare case of mammary-type myofibroblastoma of the tongue with a review of the literature.
Assuntos
Adulto , Humanos , Biópsia , Mama , Desmina , Diagnóstico , Cabeça , Extremidade Inferior , Pescoço , Neoplasias de Tecido Muscular , Recidiva , Tórax , LínguaRESUMO
In the present study, we successfully demonstrated for the first time the existence of cardiac proteomic differences between non-selectively bred rats with distinct intrinsic exercise capacities. A proteomic approach based on two-dimensional gel electrophoresis coupled to mass spectrometry was used to study the left ventricle (LV) tissue proteome of rats with distinct intrinsic exercise capacity. Low running performance (LRP) and high running performance (HRP) rats were categorized by a treadmill exercise test, according to distance run to exhaustion. The running capacity of HRPs was 3.5-fold greater than LRPs. Protein profiling revealed 29 differences between HRP and LRP rats (15 proteins were identified). We detected alterations in components involved in metabolism, antioxidant and stress response, microfibrillar and cytoskeletal proteins. Contractile proteins were upregulated in the LVs of HRP rats (α-myosin heavy chain-6, myosin light chain-1 and creatine kinase), whereas the LVs of LRP rats exhibited upregulation in proteins associated with stress response (aldehyde dehydrogenase 2, α-crystallin B chain and HSPβ-2). In addition, the cytoskeletal proteins desmin and α-actin were upregulated in LRPs. Taken together, our results suggest that the increased contractile protein levels in HRP rats partly accounted for their improved exercise capacity, and that proteins considered risk factors to the development of cardiovascular disease were expressed in higher amounts in LRP animals.
Assuntos
Animais , Masculino , Ratos , Condicionamento Físico Animal/fisiologia , Corrida/fisiologia , Proteínas/metabolismo , Testes de Função Cardíaca/métodos , Miocárdio/metabolismo , Tamanho do Órgão , Ratos Endogâmicos , Espectrometria de Massas , Eletroforese em Gel Bidimensional , Proteínas/isolamento & purificação , Proteínas Contráteis/metabolismo , Proteínas do Citoesqueleto/metabolismo , Proteômica , Desmina/metabolismo , Ventrículos do Coração/metabolismo , Proteínas de Choque Térmico/metabolismoRESUMO
BACKGROUND: Primary endobronchial smooth muscle tumors (SMTs), which are extremely rare, include endobronchial leiomyomas and leiomyosarcomas. Clinically, SMTs present with signs and symptoms of bronchial obstruction, and lack specific radiological findings. Thus, histopathological examination is required for accurate diagnosis as well as for tumor grading. We examined the histomorphological and immunohistochemical features of endobronchial SMTs and highlighted pitfalls in diagnosis, particularly when using small biopsies. METHODS: Cases of primary endobronchial SMTs diagnosed at our Institute over the last 6 years (2012–2017) were retrieved from the departmental archives. Histopathological features and immunohistochemistry performed for establishing the diagnosis were reviewed. RESULTS: Five cases of SMTs occurring in endobronchial locations were identified. These included three cases of leiomyoma, and two cases of leiomyosarcoma. The age distribution of patients ranged from 13 to 65 years. Leiomyomas showed more consistent staining with smooth muscle markers (smooth muscle actin, desmin, and smooth muscle myosin heavy chain), while tumors of higher grade showed variable, focal staining, leading to erroneous diagnosis, especially on small biopsies. CONCLUSIONS: The diagnosis of endobronchial SMTs relies on histopathological examination, for both confirmation of smooth muscle lineage and determination of the malignant potential of the lesion. Appropriate immunohistochemical panels including more than one marker of smooth muscle differentiation are extremely valuable for differential diagnosis from morphological mimics, which is necessary for instituting appropriate management.