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Biomedical subjects

C Grandi

Publications and source records attributed to C Grandi.

16 recordsLinked to original sources

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

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

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

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

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

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

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

[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

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

Prognostic significance of lymphatic spread in head and neck carcinomas: therapeutic implications.

A series of 618 patients with neck dissections were performed in 455 consecutively admitted patients with head and neck carcinomas at the Istituto Nazionale Tumori, Milan, from 1976 to 1978. Clinical and pathologic node factors were considered in an effort to correlate lymph node involvement with prognosis. Actuarial survival decreased with the increase in the size of nodes, although no significant difference was found for all categories and the prognosis was poor when nodes were greater than 5 cm and/or hypomobile (33%, 5-year survival). The presence of histologically proven neck metastases significantly reduces the 5-year survival, and the presence of distant metastases correlates directly with the pathologic staging of neck nodes.

Actuarial Analysis

The diagnostic usefulness of electron microscopy investigation of orbital embryonal rhabdomyosarcomas.

The ultrastructural study of three malignant orbital tumors, only one of which was correctly diagnosed as embryonal rhabdomyosarcoma upon histologic examination, is reported. In all 3 cases electron microscopic investigation revealed the presence of rhabdomyoblasts. These are easily recognizable in one case in which the diagnosis was made on the basis of the optical microscopic study. The other two cases needed further tests to evince rhabdomyoblasts. The importance of an ultrastructural study for a histogenetic characterization of this kind of tumor is emphasized. As far as embryonal rhabdomyosarcomas are concerned the electron microscopic study is possible, and it gives useful results even when material fixed with routine histologic methods (formalin, Bouin's solution) are used.

Child