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The author has carried out a karyometric analysis of intertissue correlations between "epithelium-mesenchyma" of the humanoral cavity on 68 series of histological sectio of human embryos and prefetuses, measuring 2,5-70,0 mm of the parietococcygeal length (PCL), aged 3-12 weeks of intrauterine development (levels X-XII of development according to Stritter and stages 9-23 of Carnegie's Institute). It has been established that prior to the appearance of morphological differences between varions versions of the epithelia and mesenchymal derivatives of the oral cavity the cell nuclei significantly differ by their dimensions. The most differentiated tissues of the human oral cavity have cells with nuclei of smallest sizes., На 68 сериях гистологических срезов зародков и предплодов человека 2,5-70,0 мм теменно-копчиковой длины, возрастом 3-12 нед. внутриутробного развития (X-XII уровни развития по Стритеру и 9-23 стадии институту Карнеги), проведен кариометрический аналез межтканевых взаимоотношений "эпителей-мезенхима" ротовой полости. Установ-лено, что до появления морфологических отличтей между разными вариантами эпителиев и походных мезенхимы полости рта ядра клеток уже вероятно отличаются размерами. Наиболее дифференцированные ткани ротовойполости человека в раннем периоде онтогенеза имеют клетки с ядрами самых маленьких размеров., На 68 серіях гістологічних зрізів зародків і передплодів людини 2,5-70,0 мм тім'яно-куприкової довжини, віком 3-12 тиж.внутрішньоутробного розвитку (X-XII рівні розвитку за Стрітером та 9-23 стадії інституту Карнегі), проведено каріометричний аналіз міжтканинних взаємовідношень "епітелій-мезенхіма" ротової порожнини. Встановлено, що до появи морфологічних відмінностей між різними варіантами епітеліїв і похідних мезенхіми ротової порожнини ядраклітин вже вірогідно різняться розмірами. Найбільш диференційовані тканини ротової порожнини людини в ранньому періоді онтогенезу мають клітини з ядрами найменших розмірів.

Objective This study aims to investigate the mechanism of transforming growth factor-β1 (TGF-β1) in promoting angiogenesis through endothelial-to-mesenchymal transition (EndMT). Methods The mesenchymal transition of human umbilical vein endothelial cells (HUVECs) was induced by TGF-β1. The angiogenesis, migration, and proliferation of HUVECs undergoing EndMT were examined by tube formation assay, scratch assay, Transwell assay, and CCK-8 assay. Results The outcomes revealed that EndMT promoted angiogenesis, migration, and proliferation of HUVECs and the secretion of the vascular endothelial growth factor (VEGF) of HUVECs. Phosphorylated AKT (p-AKT) increased in EndMT by inhibiting the mitigation of angiogenesis. Conclusion EndMT induces angiogenesis by promoting the secretion of VEGF, and p-AKT participates in this regulation.

Myxoid liposarcoma is the second most common type of liposarcoma, normally located in deep tissues of the lower extremities and rarely in the mesenchyma of abdomen and pelvis We present a patient who, incidentally, showed a large pelvis mass. CT and MR revealed a loculated lesión with hypodense areas and very high signal in T2 respectively as well as heterogeneous contrast enhancement. The imaging findings of pelvic myxoid liposarcoma are nonspecific, but nevertheless a painless mesenchymal mass should be considered when we see lesions of myxoid aspect in the pelvic area without a clear relationship with defined anatomic structures. Keywords: Myxoid, Liposarcoma, Pelvic tumors, Mesenchymal

Primary synovial sarcoma arising in the anterior abdominal wall is rare and is a rare extra-articular tumor site. It should be considered in the differential diagnosis of anterior abdominal wall masses. It is a rare malignant mesenchymal tumor. It commonly occurs in adults in the extremities in close association with joint capsule, tendon sheaths, bursae and fascial structures. Synovial sarcoma is derived from multipotent stem cells, which can differentiate into mesenchyma and epithelial structures. Three subtypes are described histologically -biphasic, monophasic, and poorly differentiated synovial sarcoma. We report a case of a 40-year-old male patient presented with swelling over the anterior abdominal wall on the right side in the lower abdomen for 1 month which was rapidly increasing in size. An ultrasound followed by computed tomography and magnetic resonance imaging of the abdomen were performed for knowing the extent of the tumor. Immunohistochemistry was suggestive of monophasic synovial sarcoma.

Multicystic renal dysplasia is a congenital cystic anomaly of the kidney caused by abnormal metanephric differentiation with immature tubules. It is surrounded by mesenchymal collars and islands of immature mesenchyma present between the cysts. The PI3K-AKT-mTOR signaling pathway is a key regulator involved in cell growth, proliferation, motility, survival, and apoptosis. Activation of the PI3K-AKT-mTOR pathway results in the survival and proliferation of tumor cells in many cancers. The aim of this study is to analyze the topographic expression of phospho-AKT, phospho-mTOR, and phospho-70S6K in renal development and in the multicystic dysplastic kidney (MCDK). A total of 17 fetal kidneys of development age from the first to the third trimester and 13 cases of pathological kidneys with MCDK were analyzed by immunohistochemistry in order to evaluate the expression of phospho-AKT (S473), phospho-mTOR, and phospho-70S6K. Phospho-AKT and phospho-mTOR were expressed early in renal development and in an identical manner for every structure derived from the ureteric bud, such as collecting ducts and urothelium. Phospho-p70S6K was expressed early in the urothelium and in glomerular mesangial cells. Later, their expressions differed according to the needs of cell proliferation and differentiation over time by becoming more selective. In MCDK, phospho-AKT, phospho-mTOR, and phospho-70S6K have the same profile: a high cytoplasmic expression in cystic epithelium, loose mesenchyma, and primitive tubes. This study demonstrates the essential and specific role of the PI3K-AKT-mTOR pathway in the formation of cysts in multicystic renal dysplasia.

Objective The aim: Thepaper wasaimedat thestudyof thebiomineralization processesofa permanentdental crown in thepostnatal period of histogenesis. Patients and methods Materials and methods: The study involved 30 culled puppies aged 30-40 days. To study the histogenesis of the germs of the permanent tooth from the cuticular epithelium in the postnatal period microscopic, electron microscopic, immunohistochemical methods of study have been used. Results Results: The studies show that in the postnatal period, the maturation of the germ of a permanent tooth starts with the synthesis of cells of the cuticular epithelium of the organic stroma, capable of subsequent mineralization. Differentiation of the proameloblasts, located on the surface of the dental papillary mesenchyma, at the early stages of histogenesis, is strongly associated with the appearance of a specific protein taftelin. Origination of secretory ameloblasts, which produce the protein enamelin, triggers the process of secondary biomineralization of the enamel. The terminal processes of the secretory ameloblasts produce the protein in the form of layers that overlap each other at a certain angle. Such layering of the structures of enamel and dentin contributes to the S-shaped maturation of the hard tooth tissues, strengthening them considerably. At the follicle stage, maturation of the dental crown, coated with cuticular epithelium, occurs. Invaginations of the cuticular epithelium form a characteristic topography of the dental crown, and enamel projections are further formed by the ameloblasts. Epitheliocytes of the inner layer of the enamel organ have desmosomal connections that allow the filtration of the salivary fluid at the stage of the enamel trophism. Conclusion Conclusions: The findings of the study suggest that, normally, due to the cuticular epithelium, filtration of the salivary fluid occurs with protein deposition on it and subsequent infiltration of the calcium salts into the subjacent enamel.

Islet transplantation is a promising treatment for selected patients with type 1 diabetes mellitus (T1DM). Hypoxia and oxidative stress are major causes of damage to transplanted islets. Mesenchymal stem cells (MSCs) have been shown to enhance cell survival mainly through paracrine secretion. However, mechanisms of action underlying the protective effects of MSCs on islets have not been fully elucidated. In this study, we investigated whether human umbilical cord-derived MSCs (huc-MSCs) could inhibit hypoxia and ROS-related cell death of neonatal porcine islet cell clusters (NICCs) and further determined the underlying molecular mechanisms. NICCs were cultured in vitro under normoxic and hypoxic (1% O2) conditions with or without MSC-conditioned medium (MSC-CM). Apoptosis of NICCs was evaluated by the AO/EB staining and Annexin V/PI flow cytometry analysis. Total and mitochondrial ROS production was detected by fluorometric assays. Western blot and the ERK pathway inhibitor, PD98059, were used to assess the possible pathways involved. The results showed that MSC-CM suppressed hypoxia-induced oxidative stress and cell death of NICCs. MSC-CM also activated several pro-survival pathways in NICCs under hypoxic conditions. Furthermore, MSC-secreted exosomes and IL-6 partially recapitulated the multifunctional benefits of MSC-CM. This study showed that huc-MSCs protected NICCs from hypoxia-induced cell death by regulating the cell redox state and cell signaling pathways. This increased understanding may enable MSCs to become a more promising adjuvant cell therapy for islet transplantation. Impact statement The utilization of mesenchymal stem cells (MSCs) is a promising approach to serve as adjuvant therapy for islet transplantation. But the inability to translate promising preclinical results into sound therapeutic effects in human subjects indicates a lack of key knowledge of MSC-islet interactions that warrant further research. Hypoxia and oxidative stress are critical factors which lead to a tremendous loss of islet grafts. However, previous studies mainly focused on other aspects of MSC protection such as inducing revascularization, enhancing insulin secretion, and reducing islet apoptosis. In this study, we aim to investigate whether MSC can protect islet cells from hypoxic damage by inhibiting ROS production and the potential underlying pathways involved. We also explore the effects of MSC-derived exosomes and IL-6 on hypoxia-injured islets. Our data provide new molecular targets for developing MSC applications, and this may ultimately promote the efficiency of clinical islet transplantation.

Özet: Tiroid bezinin hemanjiyomu nadir bir tanıdır ve literatürde günümüze kadar 35'ten az vaka yayınlanmıştır. Patogenezi tam bilinmemekle birlikte, anjiyoblastik mezenşimin kanal oluşturma yetersizliği ile ilişkili gelişimsel bir anomali olduğu ileri sürülmektedir. Mikroskobisinde, reaktif endotelyal hiperplazi, anjiyosarkom ve hemanjiyosarkomdan ayırt edilmelidir. Biz nonspesifik ultrasonografik görünüme sahip bir primer tiroid kavernöz hemanjiyomu olgusunu sunuyoruz. Sitolojik bulgular tanısal değildi ve kesin tanı spesimeninin patolojik incelemesinde kondu., Hemangioma of the thyroid gland is a rare diagnosis and less than 35 cases have been previously published in the literature. The pathogenesis is unknown but it is suggested to be a developmental anomaly which is associated with an incapability of angioblastic mesenchyma to form canals. On microscopic examination, it should be distinguished from reactive endothelial hyperplasia, angiosarcoma or hemangiosarcoma. We report a case of a primary thyroid hemangioma, with nonspesific US appearance. Cytologic findings were nondiagnostic and final diagnosis was made at pathologic examination of the hemithyroidectomy specimen.

ObjectiveRats are an early preclinical model for cartilage tissue engineering, and a practical species for investigating the effects of aging. However, rats may be a poor aging model for mesenchymal stem cells (MSCs) based on laboratory reports of a severe decline in chondrogenesis beyond young adulthood. Such testing has not been conducted with MSCs seeded in a scaffold, which can improve the propensity of MSCs to undergo chondrogenesis. Therefore, the objective of this study was to evaluate chondrogenesis of middle-aged rat MSCs encapsulated in agarose.DesignMSCs from 14- to 15-month-old rats were expanded, seeded into agarose, and cultured in chondrogenic medium with or without 5% serum for 15 days. Samples were evaluated for cell viability and cartilaginous extracellular matrix (ECM) accumulation. Experiments were repeated using MSCs from 6-week-old rats.ResultsDuring expansion, middle-aged rat MSCs demonstrated a diminishing proliferation rate that was improved ~2-fold in part by transient exposure to chondrogenic medium. In agarose culture in defined medium, middle-aged rat MSCs accumulated ECM to a much greater extent than negative controls. Serum supplementation improved cell survival ~2-fold, and increased ECM accumulation ~3-fold. Histological analysis indicated that defined medium supported chondrogenesis in a subset of cells, while serum-supplementation increased the frequency of chondrogenic cells. In contrast, young rat MSCs experienced robust chondrogenesis in defined medium that was not improved with serum-supplementation.ConclusionsThese data demonstrate a previously-unreported propensity of middle-aged rat MSCs to undergo chondrogenesis, and the potential of serum to enhance chondrogenesis of aging MSCs.

Ovarian cancer is the fifth leading cause of cancer‐related deaths. It causes approximately 125,000 deaths per year worldwide; its diagnosis is made in advanced stages resulting in a high mortality rate. The objective of the study was optimizing the isolation of cells obtained from the solid tumor and ascitic fluid of patients with ovarian cancer and the phenotype with markers related to the epithelial–mesenchymal transition. For this, the solid tumor tissue was disaggregated and cultivated with different methodologies. As a result, cell growth was obtained and epi‐immunofluorescence was performed using antibodies against E‐cadherin, EpCAM, N‐cadherin, vimentin, CD133, and CD44. The primary culture from the solid tumor was obtained using Dispase II and DMEM/F12. Finally, heterogeneity was detected in terms of the expression of mesenchymal and epithelial type markers in the two types of isolated cells. Additionally, CD133 and CD44 expression was detected, proteins associated with the tumor stem cells phenotype., The ovarian cancer cells isolated were heterogeneous. This was detected in terms of expression of mesenchymal and epithelial type markers. Additionally, CD133 and CD44 expression was detected, proteins associated with the tumor stem cells phenotype.

Traumatic brain injury (TBI) is a progressive and complex pathological condition that results in multiple adverse consequences, including impaired learning and memory. Transplantation of mesenchymal stem cells (MSCs) has produced limited benefits in experimental TBI models. Fibroblast growth factor 21 (FGF21) is a novel metabolic regulator that has neuroprotective effects, promotes remyelination, enhances angiogenesis, and elongates astrocytic processes. In this study, MSCs were genetically engineered to overexpress FGF21 in order to improve their efficacy in TBI. MSCs overexpressing FGF21 (MSC-FGF21) were transplanted to mouse brain by intracerebroventricular injection 24 h after TBI was induced by controlled cortical impact (CCI). Hippocampus-dependent spatial learning and memory, assessed by the Morris water maze test, was markedly decreased 3–4 weeks after TBI, a deficit that was robustly recovered by treatment with MSC-FGF21, but not MSC-mCherry control. Hippocampus-independent learning and memory, assessed by the novel object recognition test, was also impaired; these effects were blocked by treatment with both MSC-FGF21 and MSC-mCherry control. FGF21 protein levels in the ipsilateral hippocampus were drastically reduced 4 weeks post-TBI, a loss that was restored by treatment with MSC-FGF21, but not MSC-mCherry. MSC-FGF21 treatment also partially restored TBI-induced deficits in neurogenesis and maturation of immature hippocampal neurons, whereas MSC-mCherry was less effective. Finally, MSC-FGF21 treatment also normalized TBI-induced impairments in dendritic arborization of hippocampal neurons. Taken together, the results indicate that MSC-FGF21 treatment significantly improved TBI-induced spatial memory deficits, impaired hippocampal neurogenesis, and abnormal dendritic morphology. Future clinical investigations using MSC-FGF21 to improve post-TBI outcomes are warranted.

To investigate the effects of CYP4Z1 3′UTR in migration of breast cancer cells, a series of assays were used to confirm that overexpression of CYP4Z1 3′UTR could suppress the capacity of migration and adhesion of MCF-7 and MDA-MB-231 cells. EMT (Epithelial-mesenchymal transition)-related proteins were regulated by CYP4Z1 3′UTR. Mesenchyma markers like Vimentin, MMP-2, and MMP-9 were down-regulated, while the expression of E-cadherin was up-regulated with CYP4Z1 3′UTR overexpression. Notably, luciferase reporter and qRT-PCR assays were applied to verify that CYP4Z1 3′UTR was the potential target of miR-9. In addition, our results showed that CYP4Z1 3′UTR repressed the expression of E-cadherin in a miRNA-dependent manner. Combining with our previous study, we have discovered the underlying link between CYP4Z1 and E-cadherin. Therefore, those preliminary data suggest that CYP4Z1 3′UTR could inhibit the migration and EMT of breast cancer cells via acting as a ceRNA for E-cadherin.

Background Hemangiomas are benign vascular malformations that can involve the spine. Pure epidural hemangiomas are rare and represent only 4% of all epidural lesions. Most hemangiomas are of the cavernous type; the capillary variant is atypical, and only ten cases have been reported in the literature. Case description A 69-year-old female presented with nonspecific dorsal pain. Magnetic resonance imaging (MRI) showed a spinal epidural tumor at the T9-T10 level. Following a T9-T11 laminectomy, the lesion was completely resected en bloc. Histopathologic analysis showed a pure epidural capillary hemangioma with adipose tissue mesenchyma. Conclusions Although epidural capillary hemangiomas are extremely rare, they should be considered among the differential diagnoses of extradural, extramedullary spinal lesions. Further, they must be differentiated from other more common lesions such as meningiomas and schwannomas. The recommended surgical management is en bloc gross total excision.

ResumenIntroducciónLos tumores del estroma gastrointestinal son lesiones mesenquimatosas derivadas de las células intersticiales de Cajal. El tratamiento más efectivo en la enfermedad primaria localizada es la cirugía. Con imatinib como tratamiento neoadyuvante en las lesiones de alto riesgo o en enfermedad metastásica, la supervivencia a 5 años ha aumentado a cerca del 80%. El objetivo del presente trabajo consiste en analizar los factores pronósticos que determinan la recurrencia y la supervivencia libre de enfermedad en este tipo de tumores.Material y métodosEstudio observacional, retrospectivo y longitudinal. Pacientes del Hospital de Oncología, CMN Siglo XXI, con confirmación histológica y tratamiento quirúrgico de la lesión primaria.ResultadosSe identificaron 66 pacientes; la localización más frecuente fue el estómago (66.6%), seguido por el intestino delgado (28.7%) y el colon (1.54%). El 7.57% presentó metástasis en el momento del diagnóstico: 4.54% (3) en hígado y 3.03% (2) en peritoneo. El tamaño promedio de los tumores fue de 10.84cm (2.2 a 38cm). La tasa de supervivencia global a 5 años fue del 82%, y la tasa de supervivencia libre de recurrencia a 5 años del 61%. En el caso de la supervivencia global, la localización de la lesión fue el único factor que mostró significación estadística, con p=0.0054ConclusiónLa localización del tumor, el tamaño, el número de mitosis, el grupo de riesgo y el tratamiento adyuvante con imatinib fueron estadísticamente significativos como factores pronósticos de recurrencia de la enfermedad. La localización de la lesión fue el único factor que mostró significación estadística como factor pronóstico de supervivencia global.AbstractIntroductionGastrointestinal stroma tumours are mesenchymal lesions derived from Cajal interstitial cells. The most effective treatment in primary localised disease is surgery. With imatinib as neoadjuvant treatment in high-risk lesions or metastatic disease, 5-year survival has increased to nearly 80%. The purpose of this work is to analyse prognostic factors that determine recurrence and disease-free survival in this type of tumour.Material and methodsObservational, retrospective, longitudinal study of patients from the Oncology Hospital, CMN Siglo XXI, with histological confirmation and surgical treatment of the primary lesion.ResultsSixty-six patients were identified. The most common tumour site was the stomach (66.6%), followed by small bowel (28.7%), and colon (1.54%). At the time of diagnosis, 7.57% had metastasis: 4.54% (3) in the liver and 3.03% (2) in the peritoneum. The mean size of tumours was 10.84cm (2.2 to 38cm). Overall 5-year survival was 82%, and 5-year recurrence-free survival was 61%. In the case of overall survival, the site of the lesion was the only factor showing statistical significance, with P=.0054.ConclusionTumour location and size, number of mitoses, risk group, and adjuvant treatment with imatinib were statistically significant as prognostic factors of disease recurrence. Lesion location was the only factor that showed statistical significance as a prognostic factor of overall survival.

Mesenchymal stem cells-based therapies have shown promising effects in experimental acute respiratory distress syndrome. Different mesenchymal stem cells sources may result in diverse effects in respiratory diseases; however, there is no information regarding the best source of mesenchymal stem cells to treat pulmonary acute respiratory distress syndrome. We tested the hypothesis that mesenchymal stem cells derived from bone marrow, adipose tissue, and lung tissue would lead to different beneficial effects on lung and distal organ damage in experimental pulmonary acute respiratory distress syndrome.Animal study and primary cell culture.Laboratory investigation.Seventy-five Wistar rats.Wistar rats received saline (control) or Escherichia coli lipopolysaccharide (acute respiratory distress syndrome) intratracheally. On day 2, acute respiratory distress syndrome animals were further randomized to receive saline or bone marrow, adipose tissue, or lung tissue mesenchymal stem cells (1 × 10 cells) IV. Lung mechanics, histology, and protein levels of inflammatory mediators and growth factors were analyzed 5 days after mesenchymal stem cells administration. RAW 264.7 cells (a macrophage cell line) were incubated with lipopolysaccharide followed by coculture or not with bone marrow, adipose tissue, and lung tissue mesenchymal stem cells (10 cells/mL medium).Regardless of mesenchymal stem cells source, cells administration improved lung function and reduced alveolar collapse, tissue cellularity, collagen, and elastic fiber content in lung tissue, as well as decreased apoptotic cell counts in liver. Bone marrow and adipose tissue mesenchymal stem cells administration also reduced levels of tumor necrosis factor-α, interleukin-1β, keratinocyte-derived chemokine, transforming growth factor-β, and vascular endothelial growth factor, as well as apoptotic cell counts in lung and kidney, while increasing expression of keratinocyte growth factor in lung tissue. Additionally, mesenchymal stem cells differently modulated the secretion of biomarkers by macrophages depending on their source.Mesenchymal stem cells from different sources led to variable responses in lungs and distal organs. Bone marrow and adipose tissue mesenchymal stem cells yielded greater beneficial effects than lung tissue mesenchymal stem cells. These findings may be regarded as promising in clinical trials.

Endometrial stromal sarcoma (ESS) originates from mesenchyma or naive mesenchyma, accounting for only 0.2% of all uterine malignancies and 10–15% of uterus sarcoma. The annual incidence rate is 1–2 per million and the average age is 40–45 years old (1,2). ESS has a more preferable prognosis when compared with the more common endometrial carcinomas of epithelial origin. In 2003, ESS was classified into endometrial stromal nodule, low-grade endometrial stromal sarcoma (LGESS), high-grade ESS, undifferentiation endometrial stromal sarcoma (UES) by WHO. Early detection is necessary so to increase survive rate. Generally on magnetic resonance imaging (MRI) ESS shows the uterine body is enlarged with a well-circumscribed mass of inhomogeneous signals. In some circumstance, ESS presents hyperintensity on T2-weighted images, and isointensity relative to the myometrium on T1-weighted images. Moreover, obvious hyperintensity was observed on diffusion weighted imaging (3-5). Interestingly, in some cases, ESS may have a characteristic low-intensity rim on T2-weighted images (6). We herein present a case of a LGESS.

3104 Background: It has been demonstrated in vivo that HGF-MET signaling axis is a key molecular determinant in tumor invasion and there is a significant association in HGF expression and mesenchymal phenotype in addition to immune cell recruitment. We have developed a HGF neutralizing humanized monoclonal antibody antibody, YYB-101. The aim of this study was to determine the maximum tolerate dose (MTD), safety, pharmacokinetics (PK), and pharmacodynamics (PD) of YYB101, in patients with refractory solid tumors. Methods: YYB101 was administered intravenously at once every 2 weeks doses of 0.3, 1, 3, 5, 10, 20, 30 mg/kg, according to a 3+3 dose escalation design. Enrolled patients were planned to receive YYB101 until disease progression or intolerable toxicity. The escalation and expansion cohorts (20mg/kg) were completed. Pre-planned biomarker analysis was performed in parallel. Results: 39 heavily pre-treated refractory cancer patients were enrolled and received YYB101. No DLT was observed. YYB101 demonstrated dose proportional PK up to the dose of 30 mg/kg. No patients discontinued treatment because of adverse events. Based on PK analysis and toxicity data, the recommended dose was determined as 20 mg/kg. Of 39 evaluation patients, there was 1 confirmed partial response for > +14months (2.5%, N = 1; 1 (of 2) sebaceous carcinoma) and 17 stable disease as best response (43.5%, N = 17; 7 (of 13) CRC, 3 (of 4) melanoma, 1 (of 2) sebaceous carcinoma, 1 (of 3) gastric, 1 (of 1) basal cell carcinoma, 2 (of 10) ovarian cancer, 1 (of 1) HCC, 1 (of 1) lung cancer). Of note, 1 sebaceous carcinoma patient who have failed to ≥2+ lines of chemotherapy, have been responding to YYB for 14 months. The MET and HGF expressions by immunohistochemistry (IHC) were evaluated in 19 and 17 tumor specimens, respectively. Neither protein expressions were significant predictors for treatment response to anti-HGF antibody. However, we have observed significant reduction in HGF in responders to YYB. Two long-term responders had mesenchymal signature in RNA sequencing. Conclusions: YYB101 has a favorable safety profile in patients with refractory solid tumors and a dose-proportional PK. Efficacy data are encouraging and phase II combination therapy with YYB101 is planned to be open in metastatic CRC patients as salvage treatment. The predictive power of mesenchymal signature in YYB responders will be defined prospectively. Clinical trial information: 02499224.

Limb bud is composed of mesodermal mesenchyma or mesodermal center and one layer of dermal layer on the external surface, and it is the initial phase of upper limb development. The development of limb bud is the result of gradual changes of various signaling molecular mechanisms in three-dimensional space, and the three axes are proximo-distal, anteroposterior, and dorsoventral, which correspond to the shoulder-finger direction, thumb-little finger direction, and forearm-palm direction in limb morphology. In order to guarantee the correct development and growth of limb bud, three categories of cell groups are of vital importance: they are apical ectodermal ridge (AER) at the lateral side of the limb bud, the progress zone (PZ) at the medial side of the limb bud, and the zone of polarizing activity (ZPA) at the posterior side of the limb bud. The signaling molecules generated by the cells in these regions decide the growth directions of the adjacent cells so that the normal growth and development of upper limb is maintained (Fig. 15.1).

An 8-year-old male rhesus macaque ( Macaca mulatta) presented with unilateral enlargement of the left mandible. Radiographs revealed a marked expansion of the left mandible with a multilocular radiolucent mass with abundant osteolysis. The mass was grossly firm, fleshy, and gelatinous on the cut surface. Histologically, the mass was locally infiltrative and composed of neoplastic epithelial and mesenchymal components that stained positive for cytokeratin and vimentin, respectively. Occasional densely spherical condensations of fibroblasts resembling the cap stage of odontogenesis were present in the mesenchyma. Immunohistochemical staining with Ki-67, S-100, and CD34 indicated that both epithelial and mesenchymal components of the neoplasm had low proliferation. Alcian blue, periodic acid–Schiff, and trichrome stains showed an immature stromal component with no collagen formation. Based on the clinical, histologic, and immunophenotypic features, the tumor was identified as a locally infiltrative ameloblastic fibroma.

OBJECTIVE: Mesenchymal chondrosarcoma (MCS) of the orbit is a rare and aggressive form of chondrosarcoma. The purpose of this study was to retrospectively identify the imaging features of mesenchymal chondrosarcoma of the orbit. METHODS: This study included five patients with histologically confirmed MCS of the orbit who had undergone either CT, MRI, or both. Images were evaluated for the following: location, size, margin, CT density and presence or absence of calcification and/or ossification, MRI findings including dynamic contrast-enhancement and time-intensity curves. RESULTS: CT was performed in four of the five patients, and all four (100%) demonstrated calcification and ossification of the mass. MRI was performed in all five patients. In two patients (40%), the mass demonstrated areas of hyperintensity on T(1) weighted images. CONCLUSION: The presence of a well-defined, orbital mass with calcification and ossification on CT and, marked heterogenous enhancement and a rapid-washout pattern on dynamic MRI indicate a high probability of MCS of the orbit. In addition, MCS of the orbit can demonstrate areas of hyperintensity on T(1) weighted images, representing bone marrow fat tissue of ossification. ADVANCES IN KNOWLEDGE: MCS of the orbit is a highly malignant tumor, and early diagnosis by imaging is important. Radiologists should be aware of the imaging features of MCS of the orbit.

Fibrous dysplasia is a relative frequent benign bone disease in which there is a maturation disorder of the bone-forming mesenchyma where the lamellar bone marrow is replaced with abnormal fibrous tissue. Its diagnosis is often an accidental finding when X-ray studies or bone scans are performed for other reasons since it is usually asymptomatic. There may be complications such as deformities, pathological fractures and exceptionally malignant transformation. The differential diagnosis between malignancy and FD can be complicated and lead to late diagnosis when sarcomatous degeneration already exists. In this context, 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) may be useful in the monitoring of this condition. We present two cases of patients diagnosed with FD with suspicion of malignization of their bone lesions who were referred for complementary imaging studies of Nuclear Medicine.

In the classic view of bladder development the trigone originates from the mesoderm derived wolffian ducts while the remainder of the bladder originates from the endoderm derived urogenital sinus. Recent molecular developmental studies have questioned the veracity of this received wisdom, suggesting an endodermal origin for the trigone. To shed further light on this issue we observed mesenchymal-epithelial interactions between trigone epithelium and fetal urogenital sinus mesenchyma to infer the trigonal germ layer of origin.Mouse trigone epithelium was recombined with fetal rat urogenital sinus mesenchyma in tissue recombinant grafts that were placed beneath the renal capsule of athymic mouse hosts. Grafts were harvested at 4 weeks. Control grafts with bladder dome and ureteral epithelium were also examined. Tissues were evaluated with hematoxylin and eosin, and Hoechst dye 33258 to confirm cell species origin. Immunohistochemistry was done with androgen receptor, broad spectrum uroplakin, dorsolateral prostate secretions and seminal vesicle secretions to differentiate prostatic and seminal vesicle differentiation.Grafts of mouse trigone epithelium with fetal rat urogenital sinus mesenchyma yielded epithelial tissue that stained for dorsolateral prostate secretions but not for seminal vesicle secretions. Control grafts of bladder dome epithelium yielded the expected endodermal prostate differentiation. Control grafts of ureteral epithelium yielded the expected mesodermal seminal vesicle differentiation.The consistent finding of prostatic epithelium in tissue recombinants of trigone epithelium and fetal urogenital sinus mesenchyma reinforces the hypothesis that the trigone is derived from the endoderm and not from the mesoderm, as commonly accepted.

Identifying developmental proteins could lead to markers of bladder progenitor cells, which could be used to investigate bladder diseases. We recently reported a novel embryonic stem cell model in which to study differential protein expression patterns during bladder development. Differential and temporal expressions of the endodermal proteins known as forkhead box (Foxa1 and Foxa2) were observed. In the current study we further delineated these protein expression patterns.Epithelium was removed from the underlying mesenchyma from embryonic day 18 rat bladders. Heterospecific recombinant xenografts were created by combining embryonic stem cells plus embryonic bladder mesenchyma and placed beneath the renal capsule of mouse hosts. Grafts were harvested at 16, 18, 21, 28, 35 and 42 days, and evaluated with hematoxylin and eosin, trichrome staining, and immunohistochemistry for uroplakin, smooth muscle alpha-actin, p63, Foxa1, Foxa2 and androgen receptor.At 16 days uroplakin was detectable and it seemed to correlate with the loss of Foxa2, while Foxa1 remained at all time points. Androgen receptor was first noted in stroma at day 16. It localized to urothelial nuclei at day 21 and was undetectable at 42 days. Adjacent to the urothelium alpha-smooth muscle actin was seen on day 16 and it was localized in bundles to the periphery of the graft at later time points. Staining for basilar urothelium with p63 confirmed basilar orientation at all time points.We report the temporal spatial expression of various genes in early bladder development. This suggests that some proteins may be potential markers of bladder progenitor cells. Characterizing these markers may potentially identify bladder progenitor cells that have been directed toward a lineage path destined to become urothelial cells. Ultimately these multipotential progenitor cells could be isolated and used to study and treat diseases that affect the bladder.

Objective To study expression of NDRG3 in prostatic mesenchyma and effect of exogenous NDRG3 on prostatic stromal cells. Methods Immunohistochemical analysis was used to check expression of NDRG3 in prostate mesnenchyma. The WPMY-1 prostate immortalized mesenchyma cell line was stably-transfected with a NDRG3 gene expression vector. The NDRG3-stable transfected WPMY-1 sublines were studied along with parental and empty vector transfected WPMY-1 cells as controls. RT-PCR technology was applied to identity downstream gene expression under regulation of NDRG3 expression. Results Expression of DNRG3 was observed in prostate cancer mesenchyma, over-expression of NDRG3 in WPMY-1 cell up-regulated expression of chemotatic factors-CXCL3 and CXCL5. Conclusion Expression of stromal NDRG3 in prostate cancer specimens is significantly higher than that in benign prostatic hypertrophy (BPH) sample. There is a remarkable difference between the two groups of samples, NDRG3 may be related to angiogenesis in prostatic mesenchyma.

Experiments with 60 male and female mice of Balb/c line with mass of 18—21 g have been carried out. All manipulations, including ether euthanasia, were performed within the framework of approved rules for experiments with experimental animals. The mice were divided into four groups each of 15 animals. The groups were injected with physiological salt solution (first group), cycliphosphan (second group), Granotsit preparation (recombinant granulocytic colony-stimulating factor) (third group), and cycliphosphan in Granotsit preparation (fourth group). We have studied the total number of leucocytes in blood, bone marrow cellularity, content of granulocytic- macrophage colony-forming cells and mesenchyma l precursors with the aid of tissue culture in vitro. It has been found that the Granotsit preparation can stimulate myelopoiesis (direct specific action) and mesenchymopo iesis (indirect action) in norm. When a cytostatic agent, the studied cytokine has a protective action on both myeloid and mesenchyma l precursors of bone marrow.

Vascular endothelial growth factor (VEGF) plays an important role in inducing angiogenesis. Mesenchymal stem cells may have the potential for differentiation into several types of cells, including vascular endothelial cells. In this study, the authors explored the feasibility of applying mesenchymal stem cells transduced by the VEGF gene to the treatment of ischemic random skin flaps.Mesenchymal stem cells were isolated from Sprague-Dawley rat bone marrow and cultured in vitro. Plasmid pcDNA3.1(-)/VEGF165 containing the VEGF gene was transduced into the mesenchymal stem cells by liposome. The mesenchymal stem cells were stained with chloromethyl-1-1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanineperchlorate before the transplantation. Thirty rats were randomized into three groups. Groups A, B, and C were injected with mesenchymal stem cells transduced with pcDNA3.1(-)/VEGF165 plasmid, mesenchymal stem cells, and medium only, respectively. On the fourth day after injection, random dorsal skin flaps measuring 9 x 2 cm were elevated. The survival, neovascularization, and blood flow recovery of the flaps were detected.VEGF-transduced mesenchymal stem cells expressed VEGF highly in vitro and in vivo. Transplanted mesenchymal stem cells survived and incorporated into the capillary networks in the ischemic rat flaps. The viability measurements showed an increased percentage flap survival in group A (83.1 +/- 2.6 percent) as compared with either group B (66.4 +/- 6.1 percent) or group C (51.5 +/- 7.5 percent) (p0.01). The capillary density and the blood perfusion of the flaps in the experimental group were significantly higher than those in the other two groups (p0.01).VEGF-transduced mesenchymal stem cells can increase ischemic flap neovascularization and augment the surviving areas.

Development of the tooth is a complex and fascinating set of processes which require a sequential integration of numerous biological steps. For dental doctors, interest is particularly high, because the tooth is mainly composed of surface ectodermal epithelium and neural crest derived neuroectodermal mesenchyma, and formed by epithelial-mesenchymal interactions. There are many different types of odontogenic neoplasms. In general, proliferation, development and cytological differentiation of the neoplastic cells reflect the normal physiological development of the outbreak mother cells and/or tissues. There would appear to be a relationship between the cytological differentiation of odontogenic neoplastic cells and the physiological development and differentiation of tooth germ. We describe some morphogenesis regulation factors, such as Notch signaling, in the odontogenic neoplastic cells, in both well-differentiated and poorly-differentiated neoplasms. Our results suggest that these factors play some role in cytological differentiation or acquisition of tissue-specific characteristics in neoplastic cells.

A molekuláris genetikai eljárások, bioinformatikai módszerek és transzgenikus technológia fejlődése és robbanásszerűen terjedő alkalmazása számtalan adattal és megfigyeléssel bővítette az immunrendszert alkotó sejtekre vonatkozó molekuláris szintű ismereteinket. Ez az új tudás elsősorban az immunrendszerhez tartozó strukturált nyirokszövetek haemopoeticus eredetű komponenseire vonatkozik. A nyirokszövetek nem haemopoeticus mesenchymális sejtes alapállományát érintő vizsgálatok ugyanakkor a legutóbbi időkig ezektől messze elmaradtak. A közelmúltban elvégzett kísérletek eredményei alapján viszont ezen szekunder nyirokszöveti sejtelemeknek az embrionális korban lezajló szövetépülés során történő szöveti és funkcionális differenciálódása szintén meghatározónak bizonyult az egyén különböző immunválasz-formáiban megnyilvánuló immunológiai kompetenciájának elérésében. Az embriológiai vizsgálatok az eddig viszonylag kevéssé vizsgált stroma alapállományi szövetalkotók eredetét és fejlődési útvonalait, a limfoid sejtekkel való kölcsönhatásuk molekuláris összetevőit, az egyes limfoid-stromális mikroegységek anatómiai helyeit és ott a két szövetalkotó partner között fellépő interakciók sorrendjét írták le. A fenti folyamatok megismerésének nyilvánvaló elméleti jelentősége mellett ugyanakkor világossá vált azok hasonlósága bizonyos gyulladásos immunpatogenezisű kórképek kialakulásához is, melyek jellemző kórtani összetevője a károsodott szövetben „harmadlagos” nyirokszövet kialakulása. A haemopoeticus sejtek szöveti mikrokörnyezetüktől való függésének pontosabb megismerése a krónikus gyulladások oki terápiájának hatékonyabbá tételéhez nyújthat lehetőséget. Az összefoglaló célja ezeknek a fejlődéstani eseményeknek a bemutatása, melyek alapján az immunrendszer működésének pontosabb értelmezésében a szöveti alapállomány fejlődése és működési dinamikája legalább olyan fontos összetevőnek tűnik, mint az eddig elsősorban limfoid sejtekre mint diagnosztikus és terápiás célpontokra korlátozódó klinikai értékelés. Ezek részletesebb megismerése a nyirokszöveti alapállomány szerepének értékelése révén esetleg az ilyen immunpatogenezisű kórképek hatékonyabb kezelésének igényét és lehetőségét is felvetheti.

The microanatomy of several oribatid and one acaridid mite was studied to determine the role of free cells (haemocytes) in mites. Mites from the field as well as laboratory cultures were observed and analyzed histologically using Masson triple stain. The mites were offered various foods and kept in fluctuating moisture conditions. The presence of haemocytes was significantly correlated with the transport between internal organs of various substance. Three types of transport were recorded: (i) enzymes into the alimentary tract, including the incorporation of haemocytes into the gut walls. This process seemed to be correlated with the amount and type of food and frequently with the presence of internal extraintestinal bacteria associated with mesenchyma; (ii) metabolites, like guanine from mesenchyma into the alimentary tract followed by expulsion from the body via the gut. This process is correlated with food of high nitrogen content or dry conditions; (iii) resorption of nutrients from eggs during an induced quiescent state under unfavourable conditions by small haemocytes.

The mesonephrogenic cord disintegrates into approximately 35-40 provesicular cell masses which are in close contact with the mesonephric (Wolffian) duct (WD) on their lateral side. Here, the epithelium of the WD is columnar and shares a common basal lamina with the provesicular cell masses. This in turn gives rise to a sickle-shaped pseudostratified epithelium. The concavity of the sickle is filled by spherical cells, the transition of which into the surrounding connective tissue is continuous. The sickle is transformed into a distillation flask and becomes separated from the mesonephric duct while the spherical cells maintain a connection to it by a-for the time being-solid outlet pipe. The columnar epithelium of the mesonephric duct becomes a multilayered cone, whose surface is in contact with the outlet tube. Shortly after, a continuous lumen is formed in the cone and the outlet pipe which is delimited by cells becoming columnar and forming a basal lamina. The epithelial anlage of the nephron is clearly separated from the surrounding mesenchyma by these processes. The flask eventually becomes a corpusculum, the outlet pipe a secretory (proximal) as well as collecting tubule, and the cone of the mesonephric duct a mesoureter. The various sections display differentially differentiated epithelia that are clearly distinct from each other. The mesoureter behaves differently during differentiation of epi- and paragenitale: in the epigenitale, it is short and runs into the collecting tubules of the nephrons at the lateral side of the convolved tubules, whereas a long mesoureter crosses the dorsal side of the convolved tubules and joins the corresponding collecting tubules at the far end of the mesonephros in the paragenitale.

The identification of hereditary variants of cutaneous melanoma and analysis of the role of hereditary factors and syndromes predisposing to cutaneous melanoma were carried out. The involvement of individual nevus phenotypes in the development of this disease was determined. Based on a survey of recent molecular biological data and our studies, the etiological and genetic heterogeneity of cutaneous melanoma is reported. In relatives of patients with cutaneous melanoma and persons with multiple pigmented nevi, the malignant tumors proved to be differentiated in the direction of the neural crist tissues and/or derivatives of cutaneous mesenchyma. Based on the evidence obtained, the approaches have been developed to formation of risk groups for the purpose of early diagnostics of cutaneous melanoma.

This review summarizes our recent findings regarding the Notch signaling pathway in regulating normal eyelid morphogenesis and its role in the pathogenesis of human congenital blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES). We used genetic and molecular biological approaches to investigate the mechanism by which Notch1 activation controls expression of FoxL2, which in turn activates smooth muscle actin gene expression in periocular mesenchyma to control eyelid levator smooth muscle formation.

This paper reports four cases of nasal polyps in adult sheep from Piedmont and Sicily farms. The clinical course and post-mortem findings are described. Macroscopically numerous nasal polyps obstructing the nasal cavities, with the erosion of nasal concha, were observed. Histologically the neoformations, consisting of a different number of fusiform fibrocytic cells arranged in a variable amount of amorphous mesenchymal matrix, were located in the submucosa and covered by a simple disorganized columnar epithelium. Non-suppurative infiltration was also observed. Microbiological investigations revealed positivity for Pseudomonas aeruginosa only in one case; no bacteria were isolated in polyps collected from the other three sheep. Chronic and massive infestation by Oestrus ovis was present in three cases. The etiology and pathogenesis of these proliferations remain to be clarified, even if the authors postulate that one biological agent (bacterium or parasite) may have been responsible for the reaction of the nasal mesenchyma.

Mixed mesodermal tumours (MMTs) are relatively rare gynaecological tumours that have been poorly studied in clinical and molecular terms. They are chemosensitive (at least initially), although ultimately they have a poor prognosis. The biology of the tumour is fascinating in view of its composition of both epithelial and mesenchymal entities. We review herein the literature on the clinical and biological aspects of this malignancy.

Multipotent cells within the epithelial compartment, together with phenotypically 'plastic' mesenchyma cells (stromal stem cells), provide a repository of protected genetic information from which the structure, stability and functionality of the prostate gland can be maintained. However, mere preservation of cells in a non-dividing state is insufficient to provide the necessary reservoir of information from which the structure and function of the prostate gland can be retained or recreated. Rather, there is a constant dynamic interaction, at the level of information exchange, between stem cells (whether epithelial or mesenchymal) and their surrounding environment (both humoral and physical). Thus, with respect to epithelial stem cells, these reside within environmental 'niches' which allow their controlled and limited proliferation while preserving genomic integrity. Similar 'mesenchymal niches' are also predicted to occur, although not yet identified, thus providing the multipotent source from which the full spectrum of stromal phenotypes might be regenerated. Recent data from studies of the haematopoietic and hepato-biliary systems indicate that the potential scope of stem cells far exceeds the immediate phenotypic complement of those tissues within which they originate, being dependent upon their precise environment as well as their genomic integrity.

Primary perivascular epithelioid cell tumor (PEComa) of the liver is a very rare tumor that originates from mesenchyma. Gastrointestinal tract with perivascular distribution is the most common anatomic sites of these tumors. Only few cases of hepatic PEComa have been described so far. Malignant PEComas exhibit aggressive behavior with poor prognosis, making early diagnosis crucial. Hereby, we report a 79-year-old female with unusually located mass in the liver. A partial curative hepatectomy has been done, and PEComa was diagnosed histopathologically. No evidence of recurrence was observed during the 6-month follow-up.

Gold nanoparticles are attractive materials for use in biomedicine due to their unique properties. Increasing evidence suggests that several nanoparticles induce differentiation of human mesenchyma...

Complex 3-dimensional structures with good functions have been obtained under the primary mixcoculture of mouse hepatocytes with mouse liver fibroblasts without serum. Albumin secretion is kept above 10 μg/106 cells and urea synthesis reaches 25 μg/106 on the 7th day of culture. Avoiding serum affection, liver fibroblasts’ effects on hepatocytes’ viability, functions and 3-dimensional structure forming in primary serum-free culture have been studied. Important effects of the mesenchyma, especially the direct adherence of fibroblasts to hepatocytes, are shown.

Mesodermal determinants were investigated by cytoplasmic transfer and blastomere isolation in the eight-cell stage of Bufo arenarum. Their existence was confirmed by assaying the subequatorial cytoplasm's ability to respecify the developmental potency of animal quartets. The gray subequatorial cytoplasm, but not animal cytoplasm, is able to divert the ectodermal fate of animal quartets to several mesodermal components. The source of the transplanted cytoplasm was important in determining the category of the resulting structures. Ventral subequatorial cytoplasm from ventrovegetal blastomeres generated ventral derivatives, namely erythrocytes and mesenchyma. Dorsal subequatorial cytoplasm from dorsovegetal blastomeres produced dorsolateral derivatives, such as notochord, muscle, nephric tubules, and coelomic epithelium, including mesenchyma. On the other hand, transfer of vegetal pole cytoplasm to animal quartets resulted in the formation of groups of endoderm-like cells dispersed among epidermal cells. However, the presence of such cells did not cause any mesodermal induction. The present findings suggest the existence of cytoplasmic information responsible for mesodermal specification. The alternative hypothesis that animal blastomeres become mesoderm due to vegetal induction is questioned.