Research progress on dedifferentiated fat cells and their application in oral and maxillofacial bone tissue engineering / 口腔疾病防治

@#The identification of suitable seed cells represents a critical scientific problem to be solved in the field of oral and maxillofacial bone tissue regeneration. The application of adipose-derived stem cells (ASCs) in tissue and organ repair and regeneration has been studied extensively. In recent years, dedifferentiated fat (DFAT) cells have also shown broad application prospects in the field of bone tissue engineering. DFAT cells express stem cell-related markers and have the potential to differentiate into adipocytes, osteoblasts, chondrocytes, nerve cells, cardiomyocytes and endothelial cells. In addition, DFAT cells also have the advantages of minimally invasive acquisition, strong proliferation and high homogeneity. Currently, all studies involving the application of DFAT cells in scaffold-based and scaffold-free bone tissue engineering can confirm their effectiveness in promoting bone regeneration. However, cytological research still faces some challenges, including relatively low cell culture purity, unclear phenotypic characteristics and undefined dedifferentiation mechanisms. It is believed that with the continuous development and improvement of isolation, culture, identification and directional induction of osteogenic differentiation methods, DFAT cells are expected to become excellent seed cells in the field of oral and maxillofacial bone tissue engineering in the future.

Dedifferentiated chordoma: A rare tumor with diagnostic challenge

Chordomas are rare locally invasive malignant bone tumors arising from remnants of embryonic notochord. Dedifferentiated chordoma (DC), a rare subtype, is characterized by the presence of a sarcomatous component in conventional chordoma (CC) which may arise de novo or as a malignant transformation of previously treated chordoma. The presence of dedifferentiation warrants a poor prognosis due to distant metastasis and recurrences. De novo DCs pose a diagnostic challenge especially in small biopsies and at metastatic sites. Here, we report the case of a 45-year-old female presenting with a long history of backache and constipation, finally diagnosed as DC. Radiological as well as histomorphological pictures of the tumor posed diagnostic challenges because they can mimic other tumors occurring in a similar location. We found this case worth reporting as de novo DC is rarely reported in the literature and it has the potential to pose diagnostic as well as therapeutic challenges.

Intraperitoneal dissemination of primary dedifferentiated liposarcoma of omentum simulating an ovarian cancer – A case report

Dedifferentiated Liposarcoma (DDLPS) is a rare subtype of liposarcoma with a high preponderance of local recurrence and distant metastasis. The frequent site of DDLPS is the retroperitoneum, followed by the limbs and trunk. The primary omental DDLPS is very rare and only a few cases have been reported in the literature. Here we report a rare case of primary giant DDLPS of omentum with intraperitoneal metastasis in a 61year old woman. The present case report adds to our knowledge, that a case of intraperitoneal DDLPS can mimic ovarian cancer clinically and should be considered in the differential diagnosis of a pelvic mass in postmenopausal women.

A giant retroperitoneal liposarcoma with hemoperitoneum: A rare tumor with unusual presentation

Retroperitoneal liposarcoma (RPLS) is a rare mesenchymal tumor which accounts for 0.02–0.7% of all malignancy. The presentations of these tumors are non-specific and early diagnosis is often missed. We are reporting a rare case of 17-year-old girl who came to us with complaints of abdominal distension and other non-specific symptoms but after few hours of admission, she had acute abdomen with hemodynamic instability. She underwent emergency laparotomy and found to have a giant 25 × 20 × 10 cm ruptured retroperitoneum tumor causing hemoperitoneum. The tumor involved left ovary and fallopian tube as well. Complete resection of tumor with left salpingooophorectomy was done. The patient was kept in intensive care unit and discharged in good health after 15 days. This presentation of RPLS has not been reported yet and may demand early diagnosis and management of these tumors. The histopathology revealed dedifferentiated liposarcoma with rhabdomyosarcomatous differentiation. The patient is completely fine at 16 months of follow-up while writing this report. Again, heterologous dedifferentiation of liposarcoma with spindle cell component is a rare morphologic spectrum. Liposarcomas can have various histologic types. In dedifferentiated types, the line of differentiation needs to be identified to decide further line of treatment. Therefore, thorough histopathological analysis and immunostaining is needed. Treatment includes complete surgical resection. Role of radiotherapy and chemotherapy is debatable and is still under trial. Dedifferentiated RPLS with rhabdomyosarcomatous differentiation is a rare tumor and its presentation as acute abdomen and hemoperitoneum has never been reported previously

Detection of MDM2 gene amplification on tissue microarray-based Fluorescence In-Situ Hybridization (FISH) in well-differentiated and dedifferentiated liposarcomas, displaying a wide morphological spectrum: A validation study at a tertiary cancer referral centre

Background: Liposarcomas including atypical lipomatous tumors (ALT)/well-differentiated liposarcomas (WDLPS) and dedifferentiated liposarcomas (DDLPSs) display a histomorphological spectrum with their several diagnostic mimics. Murine double minute 2(MDM2) gene amplification characterizes ALT/WDLPS and DDLPS. Presently, there is no documented study from our subcontinent on the validation of MDM2 gene testing in these tumors. Material and Methods: Twenty-eight cases, diagnosed as ALT/WDLPS (n = 5) and DDLPSs (n = 23), along with 10 other tumors were tested for MDM2 gene amplification, using fluorescence in situ hybridization (FISH) on tissue microarrays (TMAs). Fourteen cases, diagnosed as ALT/WDLPS and DDLPS, along with 49 other tumors were tested for MDM2 immunostaining. Twenty tumors were tested for p16INK4a immunostaining. Results: FISH was interpretable in 25 (89.2%) cases. Among the 20 cases diagnosed as DDLPSs, 19 displayed MDM2 gene amplification. Among the 5 cases diagnosed as ALT/WDLPS, four showed MDM2 gene amplification. Finally, 19 cases were confirmed as DDLPS and 4 as ALT/WDLPS. Furthermore, 7/19 cases confirmed as DDLPS and all 4 cases as ALT/WDLPS tested for MDM2 immunostaining, displayed its diffuse immunoexpression, while a single case of DDLPS showed its focal immunostaining. None of the 49 control cases displayed diffuse MDM2 immunoexpression. ALL 16 DDLPSs and 4 cases of ALT/WDLPS displayed p16INK4a immunostaining. The sensitivity for diffuse MDM2 immunostaining was 87.5% in cases of DDLPS, 100% in ALT/WDLPS, and specificity was 100%. The sensitivity for MDM2 gene amplification was 94.7% in cases of DDLPS and 100% in cases of ALT/WDLPS. The sensitivity for p16INK4a was 100%. Conclusion: This constitutes the first sizable study on MDM2 testing in ALT/WDLPS and DDLPS from our subcontinent using TMAs. MDM2 gene amplification testing continues as the diagnostic gold standard for ALTs/WDLPSs and DDLPSs and is useful in cases of diagnostic dilemmas. Diffuse MDM2 (IF2 clone) and p16INK4a immunostaining, together seem useful for triaging cases for FISH.

Liposarcoma vulvar desdiferenciado con diferenciación homóloga a liposarcoma pleomórfico: reporte de caso / Dedifferentiated vulvar liposarcoma with homologous differentiation to pleomorphic liposarcoma: case report

Resumen ANTECEDENTES: Los liposarcomas son un tipo de tumor de partes blandas. El subtipo desdiferenciado es una de las variantes más comunes junto con el liposarcoma bien diferenciado. CASO CLÍNICO: Paciente de 68 años que acudió a consulta por aparición de una masa en la zona vaginal que clínicamente se diagnosticó como hernia inguinal directa. Se procedió a la resección quirúrgica de la masa. El reporte histopatológico fue de miofibrolipoma, sin atipias y con bordes libres de neoplasia. Tres años después, la paciente retornó a la consulta por reaparición de la masa y se negó a una nueva biopsia. Posteriormente, en el 2020, la paciente aceptó la resección de la masa; el reporte histopatológico fue: liposarcoma desdiferenciado con diferenciación lipoblástica homóloga a liposarcoma pleomórfico. CONCLUSIÓN: Los estudios histopatológicos son necesarios para la confirmación del diagnóstico y la resección quirúrgica es el tratamiento de elección.

Abstract BACKGROUND: Liposarcomas are a type of soft tissue tumor. The dedifferentiated subtype is one of the most common variants along with well-differentiated liposarcoma. CLINICAL CASE: A 68-year-old female patient presented for consultation due to the appearance of a mass in the vaginal area which was clinically diagnosed as a direct inguinal hernia. Surgical resection of the mass was performed. The histopathological report was myofibrolipoma, without atypia and with borders free of neoplasia. Three years later, the patient returned to the office for recurrence of the mass and refused a new biopsy. Subsequently, in 2020, the patient accepted the resection of the mass; the histopathologic report was: dedifferentiated liposarcoma with lipoblastic differentiation homologous to pleomorphic liposarcoma. CONCLUSION: Histopathological studies are necessary for confirmation of the diagnosis and surgical resection is the treatment of choice.

Cirugía de salvamento en un caso de condrosarcoma de rodilla / Salvage surgery in a case of knee chondrosarcoma

El siguiente caso, se trata de una paciente de sexo femenino que acude a consulta de traumatología por dolor de rodilla y dificultad para deambular, sin antecedente de trauma. En la radiografía anteroposterior y lateral se evidencia múltiples áreas radiolúcidas y escleróticas en meseta tibial y fémur distal derecho. La biopsia reporta: Condrosarcoma indiferenciado Grado 2. Se inicia sesiones de quimioterapia profiláctica y se planifica la cirugía de salvamento, esto ante la negativa de la paciente para aceptar la cirugía de amputación. La cirugía de reconstrucción se realizó mediante la colocación de una prótesis semiconstreñida tipo Endo Model cementada. En el posoperatorio se realizó controles y curaciones semanales, con buena cicatrización de la herida, y posteriormente rehabilitación por fisioterapia. Actualmente la paciente puede deambular con apoyo y casi de manera independiente.

The following case is a female patient who came to the trauma clinic for knee pain and difficulty walking, with no history of trauma.The anteroposterior and lateral radiograph shows multiple radiolucent and sclerotic areas on the tibial plateau and the right distal femur.The biopsy reports grade 2 undifferentiated chondrosarcoma. Prophylactic chemotherapy sessions are started and salvage surgery is planned, this given the patient's refusal to accept amputation surgery. Reconstruction surgery was performed by placing a semi-constrained, cemented endo Model type prosthesis. In the postoperative period, weekly controls and dressings were carried out, with good wound healing and later rehabilitation by physiotherapy. Actually the patient can walk with support and almost independently.

A report of two cases of dedifferentiated endometrioid carcinoma: A newly described underrecognized tumor of poor prognosis

Dedifferentiated endometrioid carcinoma or dedifferentiated endometrioid adenocarcinoma (DEAC) is defined by the presence of undifferentiated carcinoma with endometrioid carcinoma. Undifferentiated component can be misinterpreted as solid component of high-grade endometrioid carcinoma or sarcomatous component of malignant mixed mullerian tumor. We present two cases of DEAC. Two postmenopausal women underwent hysterectomy for vaginal bleeding. Microscopically, sections from the endometrial tumors showed a biphasic growth consisting of an undifferentiated component and a glandular component with sharp transition between the two components. The undifferentiated component showed focal positivity for cytokeratin and vimentin, while glandular component was diffusely positive for cytokeratin and negative for vimentin expression.

Ultrasonographic findings and diagnosis of omental dedifferentiated liposarcoma: a case report / Journal of Rural Medicine

Liposarcoma is one of the most common types of soft tissue sarcomas and can develop at any site, although omental liposarcoma is extremely rare. Omental liposarcoma has a poor prognosis because the diagnosis is difficult, until it presents as a large tumor causing severe noticeable clinical symptoms. A 51-year-old male with lower abdominal pain was referred to our clinic. Abdominal ultrasonography revealed an ill-defined, solid, heterogeneous, and hypoechoic tumor deep in the lower abdomen. Generally, liposarcomas are hyperechoic, though 20% of liposarcomas present as hypoechoic tumors. This variation might occur depending on the pathological classification. We should consider the possibility of a dedifferentiated component if ultrasonography reveals typical features of soft tissue sarcoma with hypoechoic lesion.

Comparison of Imaging and Pathologic Findings of Retroperitoneal Dedifferentiated Liposarcoma / 中华肿瘤杂志

Objective@#To investigate the imaging appearance of CT and MRI in retroperitoneal dedifferentiated liposarcoma (DDL) based on pathological findings.@*Methods@#Twelve patients with retroperitoneal DDL (13 lesions) who were surgically and pathologically confirmed were retrospectively collected in the Cancer Hospital of Chinese Academy of Medical Sciences. The correlation of CT and MRI features with histopathologic findings was analyzed.@*Results@#The CT and MRI images of retroperitoneal DDLs were large, heterogeneous soft-tissue masses, mostly lobulated (30.8%, 4/13) or multinodular (46.2%, 6/13), invading adjacent anatomic structures (46.2%, 6/13). The lesions contained different proportions of fatty and non-fatty components, and usually with clear boundaries. The CT images of dedifferentiated components showed non-fatty masses of soft tissue density or mixed density, among which ground-glass nodules may be related to mucinous components. Occasionally calcification or ossification was seen (45.5%, 5/11). The contrast-enhanced CT and MRI images of non-fatty components commonly showed intense heterogeneous enhancement (84.6%, 11/13), central cystic changes and necrosis (61.5%, 8/13), pathologically corresponding to multiple types of soft tissue sarcomas without significant specificity. The well-differentiated components were fatty masses with irregular fibrous septa or soft tissue nodules, which is pathologically corresponding to well differentiated liposarcoma. Lymph node or distant metastasis was rare.@*Conclusions@#The imaging manifestations of retroperitoneal DDLs are diverse and closely related to the proportion and distribution of different components. CT, MRI and contrast-enhanced imaging has a certain diagnostic value for retroperitoneal DDLs.

A case of retroperitoneal liposarcoma mimicking an adrenocortical carcinoma / Journal of the ASEAN Federation of Endocrine Societies

@#<p style="text-align: justify;">An adrenal mass can be a diagnostic challenge as it is not easy to differentiate the adrenal glands from other adrenal pseudotumours with only radio-imaging. We report a 28-year-old patient who was diagnosed radiologically as an adrenal cortical carcinoma after he presented with abdominal pain and fullness. Biochemically, he demonstrated secondary hyperaldosteronism. Intra-operatively there was a huge mass, inferior to a normal right adrenal, which was histopathologically proven to be a dedifferentiated liposarcoma.</p>

Clinical diagnosis and prognosis analysis of patients with endometrial dedifferentiated carcinoma: A report of 12 cases / 吉林大学学报(医学版)

Objective: To analyze the clinical diagnosis and treatment and prognosis of the patients with endometrial dedifferentiated carcinoma, and to provide the evidence for its diagnosis and treatment. Methods: The general data, auxiliary examinations, treatment methods and pathological features of 12 patients with endometrial dedifferentiated carcinoma were analyzed retrospectively; literature review was performed, and its diagnosis and treatment methods were analyzed. Results: Among the 12 patients with endometrial dedifferentiated carcinoma, 5 patients in late clinical stage all died, and the average survival time was 10 months; the remaining 7 patients in early clinical stage got a disease-free survival time of 43 months. Twelve patients underwent total hysterectomy, bilateral accessory resection and pelvic lymphadenectomy, of which 2 patients underwent omentectomy and appendectomy, with an average survival time of 8 months; a total of 10 patients remained the omentum majus and appendix, with an average survival time of 24 months. Of the 12 patients, a total of 10 patients received radiotherapy or chemotherapy with an average survival time of 32 months, and 2 patients did not receive the radiotherapy or chemotherapy with an average survival time of 16 months. Conclusion: The patients with endometrial dedifferentiation carcinoma in late clinical stage have shorter survival time and worse prognosis than the patients in early clinical stage. The survival time of patients without chemotherapy or radiotherapy is shorter and the prognosis is worse than those of the patients with chemotherapy or radiotherapy. When the lesion invades omentum majus or appendix, omentectomy and appendectomy are the routine surgical methods for endometrial dedifferentiated carcinoma; resection of the omentum majus or appendix may have no significant effect on the survival time of patient.

The Clinical Outcome of Dedifferentiated Chondrosarcoma / 대한정형외과학회잡지

PURPOSE: A dedifferentiated chondrosarcoma is a rare lethal tumor characterized by a low grade chondrosarcoma juxtaposed with a high grade dedifferentiated sarcoma, such as osteosarcoma, fibrosarcoma. The aim of our study was to document the clinical manifestation and oncologic outcomes of a dedifferentiated chondrosarcoma. MATERIALS AND METHODS: This study identified 11 patients who were diagnosed and treated for dedifferentiated chondrosarcoma between January 2007 and December 2016. The identified cohort was then reviewed regarding age, sex, symptom onset, tumor location, magnetic resonance imagings (MRIs), surgical margin, and pathologic diagnosis. The time to local recurrence and/or metastasis, follow-up duration, and the patients' final status were analyzed. RESULTS: The patients were comprised of 7 males and 4 females with a mean age of 54 years (range, 33–80 years). The location of the tumor was in the femur in 6 cases, pelvis in 4 cases, and metatarsal in 1 case. The average tumor diameter was 12.7 cm (range, 6.0–26.1 cm). At the time of diagnosis, 2 patients showed pathologic fracture; 1 patient was Enecking stage IIA, 9 patients were stage IIB, and 1 patient was stage III. Eight patients were classified as a primary dedifferentiated chondrosarcoma and 3 patients were secondary. One of the primary lesions was misinterpreted initially as a low grade chondroid lesion by MRI and underwent curettage. Local recurrence occurred in 8 cases and distant metastasis occurred in 10 cases with a mean duration of 8 months (range, 2–23 months) and 7 months (range, 1–32 months), respectively. The three-year overall survival of patients with dedifferentiated chondrosarcoma was 18%, and 10 patients died due to disease progression. CONCLUSION: Dedifferentiated chondrosarcoma developed lung metastases in the early period of the clinical courses and the prognosis was dismal.

Osteosarcoma parostal desdiferenciado en diáfisis de cúbito metastásico a pulmón / Dedifferentiated diaphyseal juxtacortical osteosarcoma of ulna with metastasis to the lung

Resumen: El osteosarcoma parostal desdiferenciado es una variante en la cual un osteosarcoma de alto grado coexiste con un osteosarcoma parostal. Se presenta el caso de un paciente femenino de 20 años; acudió con seis meses de evolución de dolor y limitación funcional en el antebrazo derecho sin causa aparente; se le realizaron radiografías, donde se observó una lesión tumoral en la diáfisis del cúbito derecho. A la exploración física, presentó dolor a la palpación en la diáfisis del cúbito y limitación a la pronosupinación. La tomografía axial computada de tórax reveló enfermedad metastásica en el lóbulo superior del pulmón izquierdo. Se le efectuó una biopsia incisional de la tumoración en el cúbito derecho, con reporte de osteosarcoma parostal desdiferenciado. Por ello, inició manejo con quimioterapia neoadyuvante con cisplatino y doxorrubicina hasta completar tres ciclos. El tratamiento quirúrgico consistió en resección intercalar de la diáfisis del cúbito derecho más reconstrucción de injerto autólogo microvascularizado de la diáfisis del peroné derecho y estabilización del injerto con placa de compresión dinámica (DCP) 3.5 mm y placa tercio de caña. En el mismo procedimiento se le efectuó metastasectomía pulmonar por toracoscopía. El reporte histopatológico postquirúrgico, con necrosis de 100%. Actualmente, la paciente se encuentra asintomática, sin datos de actividad tumoral. El osteosarcoma parostal desdiferenciado es una patología rara, pero que se debe sospechar como diagnóstico diferencial ante un osteosarcoma parostal; se debe tener en cuenta que esta enfermedad puede generar metástasis por su patrón desdiferenciado. Es importante planificar un tratamiento quirúrgico que permita una adecuada reconstrucción funcional, siempre teniendo en cuenta el principio oncológico.

Abstract: Dedifferentiated parosteal osteosarcoma is a variant in which a high grade osteosarcoma coexists with a parosteal osteosarcoma. We report the case of a 20-year-old female patient who presented with six months of evolution of pain and functional limitation of the right forearm, with no apparent cause; radiographs were performed, observing a tumoral lesion in the diaphysis of the right ulna. Physical examination showed pain upon palpation in the diaphysis of the ulna and limitation of prone-supination. Axial computed tomography of the thorax revealed metastatic disease in the upper lobe of the left lung. An incisional biopsy was performed on the right ulna, with a report of dedifferentiated parosteal osteosarcoma. Therefore, the patient was managed with neoadjuvant chemotherapy with cisplatin and doxorubicin until completing three cycles. Surgical treatment consisted of intercalary resection of the diaphysis of the right ulna, plus reconstruction of the microvascularized autologous graft of the right fibular diaphysis and graft stabilization with 3.5 mm dynamic compression plate (DCP) and one-third tubular plate. In the same procedure, pulmonary metastasectomy was performed by thoracoscopy. Post-surgical histopathological report with 100% necrosis. Currently, the patient is asymptomatic, with no evidence of tumor activity. Dedifferentiated parosteal osteosarcoma is a rare pathology, but should be suspected as a differential diagnosis in the presence of a parosteal osteosarcoma; it should be taken into account that this disease can metastasize due to its dedifferentiated pattern. It is important to plan a surgical treatment that allows an adequate functional reconstruction, always taking into account the oncological principle.

Chondrogenic Potential of Dedifferentiated Rat Chondrocytes Reevaluated in Two- and Three-Dimensional Culture Conditions

For the cartilage repair, the cell sources currently adopted are primarily chondrocytes or mesenchymal stem cells (MSCs). Due to the fact that chondrocytes dedifferentiate during 2-dimensional (2D) expansion, MSCs are generally more studied and considered to have higher potential for cartilage repair purposes. Here we question if the dedifferentiated chondrocytes can regain the chondrogenic potential, to find potential applications in cartilage repair. For this we chose chondrocytes at passage 12 (considered to have sufficiently dedifferentiated) and the expression of chondrogenic phenotypes and matrix syntheses were examined over 14 days. In particular, the chondrogenic potential of MSCs was also compared. Results showed that the dedifferentiated chondrocytes proliferated actively over 14 days with almost 2.5-fold increase relative to MSCs. Moreover, the chondrogenic ability of chondrocytes was significantly higher than that of MSCs, as confirmed by the expression of a series of mRNA levels and the production of cartilage extracellular matrix molecules in 2D-monolayer and 3-dimensional (3D)-spheroid cultures. Of note, the significance was higher in 3D-culture than in 2D-culture. Although more studies are needed such as the use of different cell passages and human cell source, and the chondrogenic confirmation under in vivo conditions, this study showing that the dedifferentiated chondrocytes can also be a suitable cell source for the cell-based cartilage repair, as a counterpart of MSCs, will encourage further studies regarding this issue.

CT findings of primary abdominal dedifferentiated liposarcoma:a comparative analysis with pathology / 实用放射学杂志

Objective To investigate the CT findings of primary abdominal dedifferentiated liposarcoma(DDL),and to improve the diagnostic accuracy.Methods CT images of 23 cases with primary abdominal DDL confirmed by pathologically were analyzed retrospectively,and the CT findings were compared with pathological results.Results The masses in 20 cases out of 23 cases were located in retroperitoneal region,2 in abdominal cavity and 1 in the pelvic extraperitoneal space.The mean diameter of the masses was 26.5 cm.CT showed the fatty and non-fatty regions in the masses.In 2 1 cases,the non-fatty region was manifested as a single mass and was located at the edge or on the surface of fatty region.In 2 cases,the non-fatty region was manifested as multiple well-defined masses and was located within the fatty region.In 2 1 cases,the fatty region showed misty density with strip and reticular septa.In 2 other cases,the fatty region showed slightly low density,mingled with some fat tissue density,which showed no enhancement with mild enhanced internal septa.In 20 cases,the non-fatty region showed soft tissue density,with mild to moderate heterogeneous enhancement.In 3 other cases,the density of non-fatty region varied between liquid and soft tissue with patchy enhancement on delayed phase.In addition,stippled calcification was found in 4 cases.Conclusion The primary abdominal DDL has relatively specific CT findings,which different dedifferentiated components pro-duce different CT characterizes.Finding well-differentiated fat components around non-fatty mass may help to improve the accuracy of diagnosis and reduce the misdiagnosis.

LDN-193189 inhibits progression and induces apoptosis in human dedifferentiated chondrosarcoma cell line NDCS-1 / 中国肿瘤临床

Objective:To clarify the effects of the BMP receptor inhibitor LDN-193189 in the dedifferentiated chondrosarcoma (DDCS) cell line NDCS-1 and to explore the anti-tumor mechanism of LDN-193189 in DDCS. Methods:NDCS-1 was treated with 5 nmol/L of LDN-193189. MTT assay and clone formation experiments were used to verify that LDN-193189 suppressed cel proliferation. Transwel and wound healing tests were performed to demonstrate that LDN-193189 inhibited cell invasion. Western blot detection was used to show that LDN-193189 inhibited the suppression of BMPR2, p-Smad1/5, and RUNX2 protein expression. Results:The BMPR2 signaling pathway was inhibited by LDN-193189;thus, cell viability and invasion were significantly suppressed. Conclusion:LDN-193189 induces the inhibition of progression in vitro via the BMPR2-p-Smad1/5-RUNX2 signaling pathway in the human DDCS cell line NDCS-1.

Cardiac Cells in Regenerative Processes in Patients with Heart Failure Due to Ischaemic Heart Disease.

Aims: This study aimed to find the cardiac cells which can participate in the processes of regeneration at patients with heart failure due to ischaemic heart disease. To investigate the participation of myosin activating protein kinases in sarcomerogenesis, because sarcomerogenesis is the crucial part of cardiomyocyte differentiation process. Study Design: Resident cardiomyocyte progenitors and dedifferentiated cardiomyocytes were found in left atrial appendages from patients with heart failure due to ischaemic heart disease. We used a cell model of fetal cardiomyocytes with the disassembly contractile apparatus to study the forming of new myofibrils (or sarcomerogenesis) regulated by myosin activating protein kinases. Place and Duration of Study: Cardiology Research and Production Center, Research Center for Obstetrics, Gynecology and Perinatology, Department of Fundamental and Applied Neurobiology of V. Serbsky Federal Medical Research Centre of Psychiatry and Narcology between June 2014 and October 2015. Methodology: We included 10 patients with heart failure due to ischaemic heart disease. Resident cardiomyocyte progenitors and dedifferentiated cardiomyocytes were found by the immunofluorescence approach and the electron microscopy. To determine the myosin activating protein kinases localization in human fetal cardiomyocytes at the 8-9 week heart gestation stage immunofluorescence approach was used. Results: We detected the cardiomyocyte progenitor cells which express c-Kit and Nkx-2.5, other cells express Mdr-1 and GATA-4. Dedifferentiated cardiomyocytes were found. It has been established that smooth muscle, nonmuscle and skeletal myosin light chain kinases are colocalized with nonmuscle myosin in premyofibrils in fetal human cardiomyocytes. Conclusion: We demonstrated that the heart of patients with heart failure due to ischaemic heart disease contains the progenitor resident cardiomyocytes and dedifferentiated cardiomyocytes. These cardiac cells possibly can proliferate and differentiate to mature cardiomyocytes and recover heart function and structure after injury. Myosin activating protein kinases may contribute in myofibril formation during the cardiomyocyte differentiation.

Vitamin C enhanced myocardial differentiation of dedifferentiated fat cells / 中国病理生理杂志

[ ABSTRACT] AIM:In order to observe the myocardial differentiation capacity of the dedifferentiated fat ( DFAT) cells treated with vitamin C in vitro.METHODS: DFAT cells were dedifferentiated from the mature rat adipocytes with ceiling adherent culture.The DFAT cells of passage 3 were used in the study.Vitamin C and/or neonatal rat heart tissue lysate were added into the culture medium to induce myocardial differentiation for 3 weeks.The cell morphology was ob-served under microscope.The myocardial-specific markers, such as cTnT, GATA-4 and NKx2.5, were examined by the methods of immunofluorescence, PCR and Western blot.RESULTS:Mature rat adipocytes dedifferentiated into fibroblast-like DFAT cells after ceiling adherent culture.The DFAT cells spontaneously differentiated into cardiomyocyte-like cells under normal culture condition with a low incidence.After treated with neonatal rat heart cell lysate, the DFAT cells be-came cardiomyocyte-like cells that had bigger size, longer shape and myotubule-structure.The expression of cTnT, GATA-4 and NKx2.5 was remarkably increased at both mRNA and protein levels as compared with the normal cultured DFAT cells.The expression of cTnT, GATA-4 and NKx2.5 was further increased in DFAT cells after treating with vitamin C.No spontaneous beating cell was observed.CONCLUSION:Vitamin C enhances the differentiation of DFAT cells into cardio-myocyte-like cells.

Two Cases of Dedifferentiated Chordoma in the Sacrum

Dedifferentiated chordoma (DC) is defined as a chordoma containing sarcoma components. DC is distinguished from conventional chordoma by the rapidity of tumor growth and the potential for distant metastasis. We report two cases of DC, which are developed in the sacrum. We reviewed the medical records and imaging studies of 2 patients diagnosed with DC and the literature published. In the first case, percutaneous biopsy revealed that it was conventional chordoma in the sacrum. Patient underwent radiation therapy (RT). Six years after the RT, the tumor recurred. Surgical removal was performed and the recurrent tumor was diagnosed as DC in histopathologic examination. In the second case, a patient underwent gross total resection of sacral tumor, which was diagnosed with conventional chordoma. Aggravated tumor was detected after 4 months, and patient underwent reoperation. The second operation revealed the transformation of the tumor into DC. The survival time of the patients after the diagnosis was 10 and 31 months. Dedifferentiated chordoma is a rare and highly aggressive tumor. De novo type exists, but it usually transformed from recurrent chordoma after surgical resection or radiation.