The differentiation stage of p53-Rb-deficient bone marrow mesenchymal stem cells imposes the phenotype of in vivo sarcoma development.

Increasing evidence suggests that mesenchymal stem/stromal cells (MSCs) carrying specific mutations are at the origin of some sarcomas. We have reported that the deficiency of p53 alone or in combination with Rb (Rb(-/-) p53(-/-)) in adipose-derived MSCs (ASCs) promotes leiomyosarcoma-like tumors in vivo. Here, we hypothesized that the source of MSCs and/or the cell differentiation stage could determine the phenotype of sarcoma development. To investigate whether there is a link between the source of MSCs and sarcoma phenotype, we generated p53(-/-) and Rb(-/-)p53(-/-) MSCs from bone marrow (BM-MSCs). Both genotypes of BM-MSCs initiated leiomyosarcoma formation similar to p53(-/-) and Rb(-/-)p53(-/-) ASCs. In addition, gene expression profiling revealed transcriptome similarities between p53- or Rb-p53-deficient BM-MSCs/ASCs and muscle-associated sarcomagenesis. These data suggest that the tissue source of MSC does not seem to determine the development of a particular sarcoma phenotype. To analyze whether the differentiation stage defines the sarcoma phenotype, BM-MSCs and ASCs were induced to differentiate toward the osteogenic lineage, and both p53 and Rb were excised using Cre-expressing adenovectors at different stages along osteogenic differentiation. Regardless the level of osteogenic commitment, the inactivation of Rb and p53 in BM-MSC-derived, but not in ASC-derived, osteogenic progenitors gave rise to osteosarcoma-like tumors, which could be serially transplanted. This indicates that the osteogenic differentiation stage of BM-MSCs imposes the phenotype of in vivo sarcoma development, and that BM-MSC-derived osteogenic progenitors rather than undifferentiated BM-MSCs, undifferentiated ASCs or ASC-derived osteogenic progenitors, represent the cell of origin for osteosarcoma development.

[Malignant melanoma of the nasal cavity. Retrospective study. The analysis of p53 and p16INK4 expression]. / Melanoma maligno de fosas nasales. Estudio retrospectivo. Análisis de la expresión de p53 y p16INK4.

Five cases of malignant melanomata of the nasal cavities have been diagnosed and studied at ENT--and Anatomopathological Departments, between 1990 and 1997, the group ranging from 65 to 90 years, middle age 74.2. Paramount symptoms were epistaxis and lack of pain in all patients. Radical surgery was performed only in one case, followed by radiotherapy; the remainder were submitted to palliative treatment. We have reviewed the literature and also an immunohistochemical analysis about p53, p16INK4 and Rb oncogenes with the aim to establish its importance in these tumor's type. The whole group have showed high levels of p53 and MIB-1 and 60 percent a loss of oncogen p16 expression.

[Gas gangrene due to Clostridium septicum in a patient with an occult colonic neoplasm. A case report and review of the literature]. / Gangrena gaseosa por Clostridium septicum en un paciente con neoplasia de colon oculta. Presentación de un caso y revisión de la literatura.

A case of gaseous gangrene by Clostridium septicum associated with colorectal cancer is presented. The patient evolved rapidly towards septic shock and death. Autopsy showed occult neoplasm and pelvic and retroperitoneal myonecrosis. An exceptional finding was that of myocarditis in which thick gram-positive bacilli were identified. A review of the literature was carried out regarding the pathogenesis and clinical manifestations of this disease. The association of colonic neoplasm and Clostridium septicum may be related with the sensitivity of the cells of this neoplasm to the toxins of the microorganisms. The usefulness of this cytotoxicity is being tested in the therapeutic reduction of tumoral mass. With respect to clinical attitude, all the authors agree on the need for clinical suspicion as to the possible existence of occult colon neoplasm in individuals with septic shock by gaseous gangrene with no obvious entry site. Diagnosis is performed by imaging techniques with barium enema and if this is normal colonoscopy is carried out. Emergency treatment consists in laparotomy with resection of the neoplasm and debridement of the area accompanied by hyperbaric oxygen and antibiotics.