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Biomedical subjects

Giuseppe Grasso

Publications and source records attributed to Giuseppe Grasso.

7 recordsLinked to original sources

In situ AP/MALDI-MS characterization of anchored matrix metalloproteinases.

Several different procedures are available for the immobilization of proteins on solid supports, as many advantages derive from this approach, such as the possibility to develop new protein solid-state assays. Enzymes that are anchored on gold surfaces can interact with several different molecules in a tag-free environment, opening the way to surface plasmon resonance (SPR) investigations. Nevertheless, it is often important to know the identity of the affinity-retained analyte, and mass spectrometric analysis, via its unique molecular mass identification, represents a very valuable complementary method. There are many pieces of evidence to suggest that matrix metalloproteinases (MMPs) are involved in normal and pathological processes, including embryogenesis, wound healing, inflammation, arthritis and cancer, but presumably also exhibiting other functions. The search for new inhibitors of MMPs has prompted research towards the development of new solid-state assays for the rapid evaluation of MMP activity. We have already reported the possibility of measuring the activity of MMP-1 anchored on solid support by coupling SPR with ESI-MS analysis. In this work, we show the in situ atmospheric pressure (AP) MALDI-MS characterization of MMPs anchored on a gold chip with known surface coverage. The study extends the MS analysis to different proteins, and sequence coverage is reported for different digestion and MS procedures.

Atmospheric Pressure↗

Hematuria as the presenting symptom of a metastatic thyroid cancer.

A 67-year-old man is presented who was admitted to our hospital for the onset of hematuria and acute urinary retention and who was found to have a 10-cm solid mass in the right obturator fossa compressing the bladder wall. Histology revealed the presence of a distant metastases from thyroid cancer. To the best of our knowledge, this is the first case of a thyroid cancer presenting with hematuria and acute urinary retention caused by distant metastases to intrapelvic soft tissue.

Acute Disease↗

Activity of anchored human matrix metalloproteinase-1 catalytic domain on Au (111) surfaces monitored by ESI-MS.

Matrix metalloproteinases (MMPs) are a family of Zn-dependent endo-peptidases known for their ability to cleave several components of the extracellular matrix, but which can also cleave many non-matrix proteins. There are many evidences that MMPs are involved in physiological and pathological processes, and a huge effort has been put in the development of possible inhibitors that could reduce the activity of MMPs, as it is clear that the ability to monitor and control such activity plays a pivotal role in the search for potential drugs aimed at finding a cure for several diseases such as pulmonary emphysema, rheumatoid arthritis, fibrotic disorders and cancer.A powerful method currently available to study enzyme-inhibitor interactions is based on the use of the surface plasmon resonance (SPR) technique. When MMP interactions are studied, a procedure by which inhibitors are normally anchored on sensor chips and SPR technique is used in order to study their interaction with MMPs molecules is usually followed. This is because it is currently believed that MMPs cannot be anchored on the sensor-chip surface without losing their activity. However, this approach gives rise to problems, as the anchoring of low-molecular-weight inhibitors on gold surfaces easily affects their ability to interact with MMPs. For this reason, the anchoring of MMPs is highly desirable.A new experimental protocol that couples the Fourier transform-SPR (FT-SPR) technique with electrospray ionization-mass spectroscopy (ESI-MS) is described here for the evaluation of the activity of MMP-1 catalytic domain (cdMMP-1) anchored on gold surfaces. The cdMMP-1 surface coverage is calculated by using FT-SPR and the enzyme activity is estimated by ESI-MS. The proposed method is label-free.

Catalytic Domain↗

TRAIL is expressed in the brain cells of Alzheimer's disease patients.

Tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL) is a novel cytokine characterized by selective killing activity against tumour cells. We recently found that beta-amyloid-induced apoptosis in a human neuronal cell line was mediated via induction of TRAIL. Here, we show that TRAIL is specifically expressed in the brain of Alzheimer's disease (AD) patients and completely absent in the brain of non-demented patients. TRAIL-like immunoreactivity was localized in AD affected regions, such as cerebral cortex, often in the proximity of Congo-red-positive amyloid plaques. These findings suggest that neurons represent an independent and potential source of TRAIL, suggesting that the latter acts redundantly with other noxious stimuli in neurodegenerative diseases characterized by amyloidosis and neuroinflammation.

Alzheimer Disease↗

Chemical shift anisotropy amplification.

A new NMR experiment which allows a measurement of the chemical shift anisotropy (CSA) tensor under magic angle spinning (MAS) is described. This correlates a fast MAS spectrum in the omega2 dimension with a sideband pattern in omega1 in which the intensities mimic those for a sample spinning at a fraction of the rate omega r/N, and these sidebands result from an amplification by a factor N of the modulation caused by the CSA. Standard methods can be used to extract the principal tensor components from the omega1 sideband patterns, and the nature of the experiment is such that the use of a large number of t1 increments can be avoided without compromising the resolution of different chemical sites. The new experiment is useful for accurately measuring narrow shift anisotropies.

Algorithms↗

Liver metastases from lung cancer: is surgical resection justified?

Resection of the liver for metastatic lesions has largely been done for secondary colorectal or neuroendocrine tumors, and there is little information of its value for other lesions. Recent improvements in hepatic surgery have made resection of metastases a safe procedure and it should certainly be considered whenever there is an isolated lesion. We report the case of a successful resection of an isolated secondary hepatic lesion from a lung primary tumor, which was resected approximately 4 years beforehand. A review of the literature demonstrates that although early reports of similar procedures were not favorable, more recent reports reinforce the value of an aggressive approach in favorable cases.

Adenocarcinoma↗

Primary adrenocortical carcinoma and delayed liver metastasis: is the surgery alone the right treatment? Case report.

Adrenocortical carcinoma is a very rare tumor which can develop at any age in either sex, with an estimated incidence of 0.5-2 new cases per million per year. Only few cases of adrenocortical carcinoma are reported in the literature, probably because the differential diagnosis between malignant and benign mass is not easy. Surgery represents the treatment of choice for adrenocortical carcinoma and for its possible recidivisms. We report the case of a 36-year-old female patient affected by adrenocortical carcinoma, operated on in 1999 and re-operated on in 2002 for a liver metastasis of the same tumor, without any other treatment. This case may be interesting for its rarity as well as for the several difficulties of the diagnosis and the choice of treatment. In conclusion, the follow-up of these patients is mandatory due to the difficulties of diagnosis and curative surgery represents the best choice of treatment.

Adrenal Cortex Neoplasms↗