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Biomedical subjects

R Manzoni

Publications and source records attributed to R Manzoni.

8 recordsLinked to original sources

Ras-dependent carbon metabolism and transformation in mouse fibroblasts.

Mutational activation of ras genes is required for the onset and maintenance of different malignancies. Here we show, using a combination of molecular physiology, nutritional perturbations and transcriptional profiling, that full penetrance of phenotypes related to oncogenic Ras activation, including the shift of carbon metabolism towards fermentation and upregulation of key cell cycle regulators, is dependent upon glucose availability. These responses are induced by Ras activation, being specifically reverted by downregulation of the Ras pathway obtained through the expression of a dominant-negative Ras-specific guanine nucleotide exchange protein. Our data allow to link directly to ras activation the alteration in energy metabolism of cancer cells, their fragility towards glucose shortage and ensuing apoptotic death.

Animals↗

Acquired glucose sensitivity of k-ras transformed fibroblasts.

Mutational activation of the ras gene is critical for the onset of different malignant phenotypes. We constructed a dominant negative mutant (GEF-DN) of a Ras activator protein (guanine nucleotide-exchange factor) that upon over-expression in k-ras transformed NIH 3T3 fibroblasts strongly reduces intracellular Ras*GTP, reverting these cells to wild-type phenotype for morphology, anchorage-independent growth and reduction of tumour formation in nude mice. Here we review evidence showing that the enhanced proliferation potential of NIH-ras cells requires high initial glucose concentration in the medium and sustained Ras pathway activation. The exquisite sensitivity of NIH-ras fibroblasts to a shortage in nutrient and energy supply highlights an acquired fragility of cancer cells that may be exploited for therapeutic purposes.

Animals↗

[A case of meningococcal sepsis].

We describe a 7-years boy by with a meningococcal sepsis due to Neisseria Meningitidis, with very serious evolution of cutaneous necrosis, initial D.I.C. and heart failure. The clinical picture do not improve with antibiotic therapy (CAF-penicillin), but the association ceftriaxone + tobramycin results in rapid improvement. The cutaneous necrosis, especially evident on gluteus, arms and legs, were treated locally with AgNO3 and penicillin-solution. After 4 weeks of treatment, also this cutaneous involvement improved and now the boy is healthy, without residual signs neither systemic nor cutaneous.

Acute Disease↗

[Relapsing polychondritis. Apropos a case].

Relapsing polychondritis is a rare disease of undetermined cause. The most frequently seen symptom is redness and swelling of cartilaginous ear, followed by cartilage inflammation elsewhere in the body and inflammation of special sense organs. This report describes recurrent attacks of relapsing polychondritis in one patient, who responded to low doses of corticosteroid therapy. The great relevance of cutaneous vasculitis in our patient, lead us to suggest that PR may fall in to the spectrum of systemic vasculitis.

Aged↗