Dahlmcleod8146

The self-renewal transcription factor Nanog and the phosphoinositide 3-kinase (PI3K)-Akt pathway are known to be essential for maintenance of mesenchymal stem cells. We evaluated their contribution to the maintenance of CD133(+) cancer stem-like cells (CSCs) and spheroid-forming cells in patient-derived cell lines from three human sarcoma subtypes HT1080 fibrosarcoma, SK-LMS-1 leiomyosarcoma, and DDLS8817 dedifferentiated liposarcoma. selleck Levels of Nanog and activated Akt were significantly higher in sarcoma cells grown as spheroids or sorted for CD133 expression to enrich for CSCs. shRNA knockdown of Nanog decreased spheroid formation 10- to 14-fold, and reversed resistance to both doxorubicin and radiation in vitro and in H1080 flank xenografts. In the HT1080 xenograft model, doxorubicin and Nanog knockdown reduced tumor growth by 34% and 45%, respectively, and the combination reduced tumor growth by 74%. Using a human phospho-kinase antibody array, Akt1/2 signaling, known to regulate Nanog, was found to be highly activated in sarcoma spheroid cells compared with monolayer cells. Pharmacologic inhibition of Akt using LY294002 and Akt1/2 knockdown using shRNA in sarcoma CSCs decreased Nanog expression and spheroid formation and reversed chemotherapy resistance. Akt1/2 inhibition combined with doxorubicin treatment of HT1080 flank xenografts reduced tumor growth by 73%. Finally, in a human sarcoma tumor microarray, expression of CD133, Nanog, and phospho-Akt were 1.8- to 6.8-fold higher in tumor tissue compared with normal tissue. Together, these results indicate that the Akt1/2-Nanog pathway is critical for maintenance of sarcoma CSCs and spheroid-forming cells, supporting further exploration of this pathway as a therapeutic target in sarcoma.Osteosarcoma (OS) is the most common primary malignant bone tumor in children and adolescents. Although activator of HSP90 ATPase activity 1 (AHA1) is reported to be a potential oncogene, its role in osteosarcoma progression remains largely unclear. Since metabolism reprogramming is involved in tumorigenesis and cancer metastasis, the relationship between AHA1 and cancer metabolism is unknown. In this study, we found that AHA1 is significantly overexpressed in osteosarcoma and related to the prognosis of osteosarcoma patients. AHA1 promotes the growth and metastasis of osteosarcoma both in vitro and in vivo. Mechanistically, AHA1 upregulates the metabolic activity to meet cellular bioenergetic needs in osteosarcoma. Notably, we identified that isocitrate dehydrogenase 1 (IDH1) is a novel client protein of Hsp90-AHA1. Furthermore, the IDH1 protein level was positively correlated with AHA1 in osteosarcoma. And IDH1 overexpression could partially reverse the effect of AHA1 knockdown on cell growth and migration of osteosarcoma. Moreover, high IDH1 level was also associated with poor prognosis of osteosarcoma patients. This study demonstrates that AHA1 positively regulates IDH1 and metabolic activity to promote osteosarcoma growth and metastasis, which provides novel prognostic biomarkers and promising therapeutic targets for osteosarcoma patients.

Schwannomas are the second most common type of intra-dural lesions involving the thoracic spine. They are frequently seen as solid and heterogeneous lesions. Totally cystic thoracic schwannomas represent a rare pathological schwannoma variant, with only four cases reported in the English literature to our knowledge.

We report an 80-year-old male who presented with upper back pain for 3 months. Magnetic resonance imaging (MRI) showed a cystic lesion at the level of T6-T7 with peripheral contrast enhancement. The lesion was removed in total surgically with complete resolution of the patient's symptoms.

The diagnosis of cystic schwannomas is often delayed due to the paucity of symptoms and the lack of meticulous investigation. The presence of rim enhancement on contrast-enhanced MRI may be the only clue for the diagnosis. It is important to consider cystic schwannomas in the differential diagnosis of cystic spinal lesions since the best surgical outcome is strongly related to earlier diagnosis and total resection of the lesion.

The diagnosis of cystic schwannomas is often delayed due to the paucity of symptoms and the lack of meticulous investigation. The presence of rim enhancement on contrast-enhanced MRI may be the only clue for the diagnosis. It is important to consider cystic schwannomas in the differential diagnosis of cystic spinal lesions since the best surgical outcome is strongly related to earlier diagnosis and total resection of the lesion.

Of the 23 cases of spinal intradural-extramedullary ependymomas which have been reported to date, 11 were diagnosed as anaplastic. Here we present a very rare case of a thoracic intradural-extramedullary (not intramedullary) anaplastic ependymoma in an adult along with a literature review.

A 29-year-old man presented with rapidly progressive gait disturbance, a sensory-deficit below the trunk and urination disorders that had begun a few months earlier. Magnetic resonance imaging of his thoracic spine revealed a dorsal-located intradural-extramedullary tumor at T4-5. The rapid deterioration of his symptoms within several months led him to refer to our department for surgery. Within one month the size of tumor increased to involve the T4-6 level, consequently worsening his gait disturbance. He underwent surgery and tumor mass was resected. However, there was leptomeningeal dissemination of the tumor cells on the surface of cord. A near-total resection was therefore achieved. Histopathology revealed the resecareful and serial follow-up is necessary for this individual.The transmission of SARS-CoV-2 is a major Public Health problem that is influenced by a number of factors. Recently it has been hypothesized that this transmission may be reduced during the summer due to the warm temperatures. On the other hand, the potential association between the high number of SARS-CoV-2 infections and air pollution is being studied. This relationship was already proven during the SARS outbreak in 2002. This article reviewed the scientific evidence to date regarding the possible influence of environmental temperature and air pollution on the transmission of SARS-CoV-2. It is concluded that the annual seasons and, therefore, the temperature do not seem to influence the spread of the virus. In addition, air pollutants facilitate infection and mortality from the virus.