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Biomedical subjects

C Grandi

Publications and source records attributed to C Grandi.

At least 19 recordsLinked to original sources
PubMed1991

Cisplatin in advanced salivary gland carcinoma. A phase II study of 25 patients.

A prospective Phase II study was carried out to test cisplatin (CDDP) as a single agent in salivary gland carcinomas. CDDP was administered (100 mg/m2) every 3 weeks to 25 consecutive patients with either recurrent or locally advanced salivary gland carcinoma. Six patients had received prior chemotherapy, and the other patients had had only surgery or radiation therapy or no treatment at all. The response rate was 18% (95% confidence interval [CI], 6% to 41%). Response duration was between 5 and 9 months. Median overall survival time was 14 months. CDDP is a moderately active drug in salivary gland carcinomas. It should be included in multidrug regimens to be tested in prospective studies, which are difficult to carry out due to the rarity of these tumors.

Adult↗
PubMed1991

Synthesis, purification, and characterization of human ciliary neuronotrophic factor from E. coli.

The cDNA for human ciliary neuronotrophic factor (CNTF) has been cloned into an expression vector under the control of the T7 promoter. The BL21 strain of E. coli was transformed with this vector. Human CNTF accounted for about 30% of the total bacterial protein after induction with isopropyl-B-D-thiogalactopyranoside. This human CNTF was purified to homogeneity from inclusion bodies by a combination of ion exchange chromatography and reverse-phase high performance liquid chromatography. The amino-terminal amino acid sequence of the purified protein was identical to the deduced amino acid sequence; however, the methionyl residue has been removed. On SDS-PAGE gels, human CNTF displayed a molecular weight of about 24 kDa, in accord with its deduced molecular mass; a pI of 5.8 indicates the acidic nature of the molecule. A proposed structure for human CNTF includes major alpha helical regions. The ED50 of purified human CNTF was approximately 30 pM, using cultured embryonic day 10 chicken dorsal root ganglion neurons; no activity was observed with neurons from embryonic day 8 ganglia. Polyclonal antibodies prepared against both a synthetic peptide of CNTF and the entire human CNTF protein recognized a single 24 kDa band on Western blots, corresponding to human CNTF. However, only the antibodies against intact CNTF blocked its biological activity. This represents the first molecular expression and purification of human CNTF.

Base Sequence↗
PubMed1988

Adjuvant chemotherapy with vincristine, cyclophosphamide, and doxorubicin after radiotherapy in local-regional nasopharyngeal cancer: results of a 4-year multicenter randomized study.

To evaluate the effect of adjuvant chemotherapy in patients with local-regional nasopharyngeal carcinoma (NPC) (squamous or undifferentiated) in complete remission at the end of curative radiotherapy (RT) 229 patients were randomized from 1979 to 1983 in a multicenter study to no further therapy (116 patients) or a combination of vincristine, cyclophosphamide, and Adriamycin (doxorubicin; Adria Laboratories, Columbus, OH) (VCA) for six monthly cycles (113 patients). The RT and RT + VCA groups were well balanced for median age (50 v 49 years), histology (undifferentiated carcinoma, 73% v 70%), tumor extent (tumor limited to nasopharynx, 57% v 57%), and nodal extent (negative nodes 26% v 24%, nodes in the lower cervical levels, 17% v 16%). RT was delivered to the nasopharynx, the base of the skull, and bilateral cervical nodes using a split course technique over 10 weeks up to the dose of 60 to 70 Gy in involved sites and 50 Gy to negative nodes. Response to RT was evaluated within 65 days post-RT treatment. Analysis at 48 months did not show significant difference between the two treatment groups in terms of relapse-free survival (RT, 55.8%, RT + VCA, 57.7%, P = .45) and overall survival (RT, 67.3%, RT + VCA, 58.5%, P = .13). The pattern of relapse was similar in the two treatment arms. Distant metastases were the cause of treatment failure in about 50% of relapsing patients. Although the results of the present study did not show any benefit from VCA administered after curative RT, combined systemic chemotherapy should be further explored due to the high incidence of local and distant failure after intensive RT.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1983

Spectroscopic study on the structure and stability of beef liver arginase.

The secondary and tertiary structure of the oligomeric arginase (EC 3.5.3.1) from beef liver was investigated by circular dichroism (CD) and fluorescence measurements. The far-ultraviolet CD spectrum of the enzyme at neutral pH is indicative of high helical content. The intrinsic fluorescence emission of the protein is due to tryptophan, the contribution of tyrosine being small. Upon excitation at 295 nm, the maximum of emission occurs at 330 nm, implying that the tryptophan residues are rather buried in a hydrophobic interior of the protein. Ethylenediaminetetraacetic acid (EDTA), which inactivates the enzyme by removing the functional Mn2+-ion from the enzyme, does not dissociate the enzyme into subunits, nor affect noticeably its secondary and tertiary structure. Inactivation occurs in the acid pH range, being complete at pH below 4. However, acidification up to pH 1.5 produced only limited changes in the far-ultra-violet CD spectrum and intrinsic fluorescence emission properties. The enzyme shows noteworthy thermal stability, as shown by measuring the residual activity after heating and by evaluating the temperature dependence of the CD signal at 220 nm and the intensity of emission fluorescence. A temperature of half inactivation (Tm) of 77 degrees was determined upon heating the enzyme at pH 7.5 in the presence of Mn2+-ions for 10 min; in the presence of EDTA, Tm is shifted to 55 degrees. Taken together, these observations indicate that the structural stability of beef liver arginase arises from a clustering of hydrophobic amino acids and from Mn2+-ion binding.

Animals↗
PubMed1980

Fluorescence properties of neutral protease from Bacillus subtilis.

The fluorescence properties of neutral protease from B. subtilis have been investigated under a variety of conditions and the results compared with those previously reported for the homologous metalloendopeptidase thermolysin (Fontana et al., 1977). In the pH range 5-9 neutral protease displayed a quite unusual fluorescence emission spectrum with a maximum near 320 nm, when excitation was at 295 nm. At this wavelength the protein fluorescence is due to tryptophan residues only, which, considering their blue-shift emission, appear rather buried in the hydrophobic protein interior. Specific removal of the functional zinc ion from the enzyme with tetraethylenepentamine does not lead to alteration of the microenvironment around tryptophan residues. On the other hand, removal of both zinc and calcium with ethylenediaminetetraacetic acid brings these residues in full contact with the aqueous solvent medium. Fluorescence quenching measurements were also used to determine the exposure of tryptophan residues in the native enzyme as well as in the presence of chelating agents and protein denaturants. Melting profile experiments carried out by monitoring the fluorescence intensity at 320 nm indicated a cooperative transition at 60-70 degrees. Temperature effects were also determined under conditions perturbed with respect to pH, guanidine hydrochloride and chelating agents. The results reveal differences in the fluorescence properties of the tryptophanyl residues of B. subtilis neutral protease relative to those of thermolysin, which are interpretable considering the location of these residues in the sequences of the two homologous proteins.

Amino Acid Sequence↗
PubMed1980

Preoperative irradiation and surgery for esophageal cancer: causes of failure.

Twenty-seven patients with squamous esophageal cancer underwent small volume, low-dose, concentrated radiotherapy followed by esophageal resection whenever possible (esophagectomy for tumors of the thoracic esophagus and esophagogastrectomy for tumors of the lower esophagus). Curative resectability was 70% (19/27) with 4 operative deaths (21%). Recurrence rate was 66% after a mean period of 16 months, and the failure pathway was nodal in 53% of the cases. Historical comparison of the data suggests that preoperative irradiation increases the curative resectability rate without changing the early recurrence rate or failure pathway. Tumors with deeper invasion of the esophageal wall, which benefit by preoperative irradiation, are probably related to greater nodal diffusion, which is partly outside of the volume that may be resected or irradiated.

Adult↗
PubMed1980

Thermolysin and Bacillus subtilis neutral protease. Conformation and stability of two homologous neutral metalloendopeptidases.

A comparative study on thermolysin from Bacillus thermoproteolyticus and neutral protease from Bacillus subtilis involving (far- and near-ultraviolet circular dichroism (CD) and immunological techniques is reported. These enzymes are homologous metalloendopeptidases, having similar size, kinetic behaviour, substrate specificity and susceptibility to inhibitors. The far-ultraviolet CD spectrum of each protein shows a minimum at 208 and a shoulder near 220 nm; differences in the extent of ellipticity, however, have been observed. Estimates of secondary structure obtained by quantitation of the far-ultraviolet CD spectra indicated a higher helicity of neutral protease relative to thermolysin. In the presence of ethylenediaminetetraacetic acid, which removes calcium and the functional zinc ion from the metalloenzymes, neutral protease is immediately denatured, whereas thermolysin maintains a globular structure, although thermolabile. On the other hand, the zinc-specific chelating agent tetraethylenepentamine does not have measurable effects on the conformation and conformational stability of either protein. Marked higher stability to temperature and guanidine hydrochloride were observed for thermolysin as compared with neutral protease, as indicated by monitoring conformational transitions with CD measurements at 220 nm. Antisera prepared in rabbits using thermolysin as immunogen do not cross-react with neutral protease, indicating differences of surface structure between the two proteins. On the basis and limitations of the techniques employed, it is proposed that the two sequentially and functionally homologous metalloendopeptidases may have similar conformations at specific regions (active and binding sites, at least) of the polypeptide chain essential for biological function, while some variability in the structure of other regions may be tolerated.

Amino Acids↗
PubMed1979

Lobectomy with bronchoplastic procedures for lung cancer.

From April 1970 to October 1977, 19 patients with lung cancer of the upper lobar bronchus orifice underwent radical lobectomy with major bronchus resection. Sleeve lobectomy was accomplished in 11 cases and wedge lobectomy in the remaining 8. The length of the free bronchial margin in the surgical specimen was less than 1 cm in 3 cases, but limited pulmonary reserve did not allow pneumonectomy. Squamous carcinoma was diagnosed in 14 patients, adenocarcinoma in 2, oat-cell carcinoma in 2, and large cell carcinoma in one. Most cases (70%) were pathological stage I. There was one operative death due to anastomotic leakage (5%), and another patient required pneumonectomy completion. Of 13 patients with non oat-cell carcinoma and adequate bronchial resection, none had local recurrence: 3 patients developed distant metastases, and 10 are alive and disease-free after a follow-up period ranging from 16 to 104 months. The authors conclude that in selected lung cancer patients lobectomy with bronchoplastic procedures is superior to pneumonectomy for tissue sparing advantages.

Adenocarcinoma↗
PubMed1977

Surgical treatment of primary breast cancer.

Radical mastectomy should be replaced by a number of different types of operation which are either more conservative or more extended according to the spread of the disease. For T1N0 cases a new procedure consisting of removal of a quadrant of the breast, with axillary dissection plus radiotherapy on the residual breast tissue, is under evaluation. In T2N0 cases modified radical mastectomy is suggested as a procedure of choice, whilst T3 cases and all N1 cases should still undergo radical mastectomy. Cases with tumor of inner quadrants with positive axillary nodes with benefit from removal of internal mammary nodes. Superradical mastectomy is limited to selected special cases with extensive lymphnode invasion. All N+ cases receive adjuvant chemotherapy (CMF). In locally advanced cases "reductive" surgery may form part of an aggressive chemotherapy programme.

Antineoplastic Agents↗
PubMed1976

Thermal properties of glyceraldehyde 3-phosphate dehydrogenase from Escherichia coli.

The molecular properties of glyceraldehyde 3-phosphate dehydrogenase from E. coli have been evaluated by circular dichroism and fluorescence emission spectroscopy measurements, with the purpose of studying the structural properties which are relevant for a comparison with the enzyme from the obligate thermophile Bacillus stearothermophilus. The enzyme is moderately resistant to heat treatment, being pratically stable when treated for 10 min at 50 degrees C and completely inactivated when heating was performed at 60 degrees C. The secondary structure of the E. coli GPDH appears to be predominatly beta-structure as judged by circular dichroism, showing a negative band centered at about 219 nm. The emission fluorescence of the enzyme shows a maximum at 333 nm upon excitation at 295 nm. In the native E. coli enzyme the tryptophan residues seem to be buried in a hydrophobic region rather than exposed to a polar environment. The structure of the enzyme did not change up to about 50 degrees C, at which temperature thermal inactivation takes place. Upon denaturation the circular dichronic signal at 219 nm gradually decreases, and a red shift of the emission maximum from 333 nm to ca. 345 nm upon heating is indicative that the native structure of the enzyme is unfolded, the tryptophan being exposed to the solvent medium. Since it has been found that the E. coli GPDH closely resembles in many of its properties the B. stearothermophilus enzyme, this bacterial enzyme seems to be useful for comparision with the thermophilic enzyme in studies of its thermostability.

Circular Dichroism↗
PubMed1976

Comparative conformational properties of thermophilic and mesophilic 6-phosphogluconate dehydrogenase.

The structural properties of 6-phosphogluconate dehydrogenase from the mesophilic bacterium E. coli and the thermophilic B. stearothermophilus are compared using circular dichroism and fluorescence emission spectroscopy. The enzymes appear to possess a similar structure which does not change on heating up to the respective temperature of stability of the enzyme. The thermostability of the two 6-phosphogluconate dehydrogenases as determined by activity measurements parallels that determined by CD with the melting profile method, indicating that the loss of biological activity in the enzymes is directly related to the unfolding of the protein molecule. The pattern of unfolding of the proteins by the action of 8 M urea suggests that a core of enhanced conformational stability exists in the B. stearothermophilus enzyme.

Circular Dichroism↗
PubMed1976

[Drug-protein interactions: physico-chemical study on the interactions between chlorpromazine and glutamate dehydrogenase].

The molecular basis of inhibition of glutamate dehydrogenase by chlorpromazine was studied by circular dichoroism, differential spectroscopy and fluorescence. Chlorpromazine appears to induce conformational changes of the enzyme at the position of aromatic amino acids, and tryptophan residues in particular are involved. On the other hand the secondary structure of the enzyme is not influenced by binding of the drug.

Binding Sites↗
PubMedDate not supplied

Analysis of prognostic factors and proposal of a new classification for nasopharyngeal cancer.

A retrospective analysis was performed on 410 patients with nasopharyngeal carcinoma of squamous or undifferentiated histotype. All patients were classified according to the classification of the American Joint Committee for Cancer Staging and End-Results Reporting (AJC) and to that of the International Union Against Cancer (UICC, Geneva, 1978). The following prognostic factors were investigated by means of a Weibull multiple regression model: sex, age, histology, primary tumor extent, and nodal metastasis extent. With the exception of sex, all factors significantly influenced survival. With regards to nodal extent, only the level of the involved nodes was a significant variable. Both AJC and UICC classifications, when applied to the entire series of patients, appeared to be unsatisfactory. The authors propose an alternative classification based on a prognostic scoring system directly derived from the Weibull model.

Female↗