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Biomedical subjects

F Molina

Publications and source records attributed to F Molina.

At least 73 records · Page 4Linked to original sources
PubMed1995

Single agent Taxol, 3-hour infusion, in untreated advanced non-small-cell lung cancer.

Currently, only a few chemotherapeutic agents have consistently produced single agent response rates greater than 15% in patients with non-small-cell lung cancer (NSCLC). Taxol has been reported in two phase II studies to have significant activity in NSCLC with response rates of 21% and 24%. Schedule infusion of 24 hours has been used to reduce allergic reactions. The study reported here was a phase II trial of Taxol given by 3-hour intravenous infusions at a 210 mg/m2 dose every three weeks in outpatients setting. It was conducted simultaneously at three centers on chemotherapy-naïve patients medicated with unresectable stage III or metastatic NSCLC. Sixty-two patients were initially enrolled; all were premedicated with dexametasone (20 mg), cimetidine (330 mg) and diphenilhydramine (50 mg), given prior to initiation of paclitaxel infusion. Fifty patients were evaluated for toxic effects and 47 for response. Sixteen partial responses (34) and one complete response (2%) were observed, for an overall response rate of 36% (95% confidence internal, 22% to 50%). Taxol was well-tolerated and none of the patients experienced allergic reaction. Granulocytopenia was generally mild. Therapy was interrupted in only two patients because of the development of grade 3 neuropathy. In our experience Taxol is one of the most active cytotoxic drugs targeting non-small-cell lung cancer.

Adult↗
PubMed1995

Stratifin, a keratinocyte specific 14-3-3 protein, harbors a pleckstrin homology (PH) domain and enhances protein kinase C activity.

The intrinsic signal(s) responsible for the onset of human keratinocyte terminal differentiation is not yet fully understood. Evidence has been recently accumulated linking the phospholipase-mediated activation of protein kinase C to the coordinate changes in gene expression occurring during keratinocyte terminal differentiation. Here we report the purification of a keratinocyte-derived protein enhancing protein kinase C enzymatic activity. The stimulator eluted as a peak with estimated molecular mass of approximately 70 kDa, while analysis by SDS-PAGE showed a 30 kDa protein migrating as a distinct doublet, suggesting the formation of a 30 kDa homodimer. The amino acid sequence analysis allowed the unambigous identification of the protein kinase C stimulator as a mixture of the highly homologous sigma (stratifin) and zeta isoforms of 14-3-3 proteins, which are homodimers of identical 30 kDa subunits. Mono Q anion exchange chromatography and immunoblot analysis further confirmed that stratifin enhances protein kinase C activity. Stratifin was originally sequenced from a human keratinocyte protein database, but its function was unknown. The pleckstrin homology domain has been recently related to protein translocation to the cell membrane as well as to functional interactions of intracellular proteins involved in signal transduction. We show here that stratifin (and 14-3-3 zeta) harbors a pleckstrin homology domain, and the consequent functional implications will be discussed.

14-3-3 Proteins↗
PubMed1995

Mandibular elongation and remodeling by distraction: a farewell to major osteotomies.

A modified technique for mandibular distraction is reported: an oblique corticotomy is made in the external cortex of the mandible at the level of the gonial angle. Two intraosseous stainless steel pins are inserted and are joined by a softer distraction screw. We make two corticotomies, one horizontal and one vertical, and insert three pins to achieve bidirectional distraction when the mandibular body and the ascending ramus are hypoplasic. This procedure has been used in 87 patients with unilateral hemifacial microsomia and 19 patients with bilateral mandibular hypoplasia. A mean elongation of 19 mm was obtained in the unilateral group. In the bilateral cases a mean vertical elongation of 7.5 mm and a mean horizontal elongation of 14 mm were obtained. A great improvement of the facial asymmetry was achieved in all the patients. The follow-up in this series varies from 3 months to 3 1/2 years (mean, 19 months in unilateral cases and 12 months in bilateral cases). No relapses have been observed.

Adolescent↗
PubMed1995

[Invasive pulmonary aspergillosis. Necropsy series].

Invasive pulmonary aspergillosis (IPA) is a severe infection which is usually diagnosed at postmortem examination. This infection occurs mainly in immunosuppressed patients, although it has also been reported in immunocompetent patients. Clinical records from patients diagnosed with IPA in our institution from 1983 to 1992 were retrospectively studied to analyse clinical and therapeutical characteristics of IPA. Sixteen episodes of IPA were recorded, all of them but one from necrotic specimens. A total of 18.7% of patients were immunocompetent, one patient had the acquired immunodeficiency syndrome (AIDS), and the remaining patients had a classical immunosuppression. Fever and dyspnea were noted in all patients; hemoptysis was recorded in 12.5% of patients. The predominant radiological pattern was a bilateral alveolar infiltrate (75%). Diagnosis was made at postmortem examination in 15 cases (93.7%), and a clinical premortem suspicion was obtained only in 25% of patients. IPA can occur in immunocompetent patients more frequently than considered until now. The suspicion index for IPA is low, even in immunosuppressed patients.

Adult↗
PubMed1995

[Neurologic manifestations of Whipple disease].

Pure neurologic Whipple's disease (WD) may be suspected by same clinical data (dementia-ophthalmoplegia-myoclonus triad, oculomasticatory myorhythmia) with support of MRI. Diagnosis is confirmed by intestinal and/or brain biopsy. Early recognition is critical in a disease that can lead to irreversible neurologic sequelae and that can potentially be cured. Despite therapy, relapses in patients with WD are common, being neurologic recurrence the most frequent and serious. Antibiotics that do not cross the blood-brain barrier are not adequate initial therapy for WD, because they predispose to neurologic relapse. Patients with WD should be treated for one year with antibiotics that cross the blood-brain barrier (such as parenteral penicillin+streptomycin, followed by oral trimethoprim-sulfamethoxazole). CNS relapse is usually resistant to therapy.

Anti-Bacterial Agents↗
PubMed1995

Single-agent paclitaxel by 3-hour infusion in the treatment of non-small cell lung cancer: links between p53 and K-ras gene status and chemosensitivity.

Currently available cytotoxic drugs are only moderately active in non-small cell lung cancer (NSCLC) and prolong survival only slightly. In two published trials, single-agent paclitaxel (Taxol; Bristol-Myers Squibb Company, Princeton, NJ) was reported to have significant activity in NSCLC, with response rates of 21% and 24%. Treatment-limiting hypersensitivity reactions, however, were noted in a phase I trial of paclitaxel given as a 3-hour infusion at doses > or = 190 mg/m2. We report the results of a phase II trial of paclitaxel given by 3-hour intravenous infusion at 210 mg/m2 every 3 weeks in an outpatient setting. The study was conducted simultaneously at three centers and included chemotherapy-naive patients with unresectable locoregional or metastatic NSCLC. The study objectives were to evaluate response rate, the potential link between p53 and K-ras gene mutations and increased paclitaxel resistance, and toxicity. Sixty-two patients were eligible for this study. All patients were premedicated with dexamethasone 20 mg given orally or intravenously 12 and 6 hours before paclitaxel infusion and cimetidine 300 mg and diphenhydramine 50 mg, both given 60 minutes prior to initiation of paclitaxel infusion. Of the 62 patients who were initially enrolled, 50 (44 men and six women) were evaluable for toxicity at interim analysis; 47 of these patients were evaluable for response. Twenty-four had squamous cell carcinoma, 20 had adenocarcinoma, and six had undifferentiated large cell carcinoma. The median age was 61 years (age range, 36 to 75 years). The median Zubrod performance status was 1 (range, 0 to 2). Seventeen (36%) patients achieved either partial or complete response. Among 24 patients with squamous cell carcinoma, eight (33%; 95% confidence interval, 15% to 61%) had a partial response. Seven (41%; 95% confidence interval, 18% to 64%) of 17 patients with adenocarcinoma had a partial or complete response. Tissue blocks were obtained for analysis of K-ras and p53 gene mutations by means of polymerase chain reaction followed by single-strand conformation polymorphism assay. Our findings indicate that mutations are associated with a poor clinical course and may be prognostic of paclitaxel resistance. Paclitaxel was well tolerated. None of the patients experienced allergic reactions. Granulocytopenia was generally mild. Therapy was interrupted in only two patients because of the development of grade 3 neuropathy. In our experience, paclitaxel is one of the most active cytotoxic drugs targeting NSCLC.

Adult↗
PubMed1994

Antiproliferative and synergistic effect of interferon alpha-2a, retinoids and their association in established human cancer cell lines.

The effect of 13-cis-retinoic acid (cRA) and all-trans-retinoic acid (tRA) used alone or in combination with interferon alpha-2a (alpha-IFN 2a) was tested on three established human cell lines: KB (epidermoid carcinoma of the oral cavity), SCC-25 (tongue squamous cell carcinoma) and MCF-7 (mammary carcinoma). Both retinoids significantly decreased cell proliferation (growth curves) and colony forming efficiency (CFE) in all cell lines, in a dose-dependent way (at a concentration ranging from 10(-5) to 10(-9) M) and differing from line to line, following the pattern: MCF-7 > SCC-25 > KB. Retinoids at any concentration (already at 10(-7) M) combined with alpha-IFN 2a (ranging from 100 to 500 IU/ml) were more effective in inhibiting cell proliferation than each of the two compounds alone. This was particularly evident with SCC-25 cells. Concerning MCF-7 cells, on the contrary, the effects produced by the association suggested a possible additive more than synergistic amplification of growth inhibition.

Breast Neoplasms↗
PubMed1994

Characteristics of the cytosol-synthesized proteins generating class-I-bound peptides.

The proteins synthesized in the cytosol are several thousand, and the number of peptides potentially able to be bound by class I molecules they can generate is therefore huge. On the other hand, the actual number of peptide-class I complexes required for CTL activation is around 200. We focused on the peptides bound by B27 molecules and by the whole class I. By comparing our results with analogous data from other laboratories, we found that 31 peptides matched protein sequences in data bases; in four cases, two peptides are derived from the same protein. The finding of four pairs of identical samples in a sampling of 31 peptides from a pool of unknown magnitude suggests that this pool is quite small. We have estimated the size of this pool by combinatorial analysis and by computer simulation, and we have found a most probable distribution of about 100 to the number of self-proteins that can actually generate peptides bound by class I molecules.

Amino Acid Sequence↗
PubMed1994

Molecular Probe Data Base (MPDB).

This paper provides an update on the contents and structure, forms and mode of data distribution of the Molecular Probe Data Base (MPDB), a database that collects and provides on-line information on the sequence, target gene, applications and bibliographic references of synthetic oligonucleotides. The recent data extension and the new means of accessing the database are discussed.

Base Sequence↗
PubMed1994

Minimal incision palatopharyngoplasty. A preliminary report.

A new palatopharyngoplasty which allows good muscular reorientation as well as elongation of the soft palate with minimal morbidity and scarring has been developed, and 66 selected patients underwent the procedure during the period September 1989 to March 1993. The most important findings were reduced operative bleeding, good length and mobility of the soft palate, and minimal scarring. A total of seven fistulas (11%) developed. Twenty-three patients (mean age 6 years and 2 months at the time of operation) underwent nasopharyngoscopy and multiview videofluoroscopy; velopharyngeal insufficiency was evident in only four (17%). Dental casts were obtained in 14 patients (mean age at the time of the operation 1 year, 3 months) who were followed up for a maximum period of two years. No postoperative orthodontic treatment was required and the width and harmony of the dental arch were maintained in all cases.

Adolescent↗
PubMed1994

Orbital hypertelorism.

Excessive distance between the orbits is only one manifestation of a complex deformity that affects several skeletal and soft-tissue structures. This article discusses the classification, preoperative planning, and surgical procedures used in the reconstruction of orbital hypertelorism.

Adult↗
PubMed1994

[Extrahepatic portal vein aneurysm and recurrent cholestasis].

Aneurysm of the portal vein is quite infrequent and its clinical manifestations is variable. The association between aneurysm of the extrahepatic portal vein and recurring obstructive jaundice has only been described on one occasion, one where there was also portal hypertension. One case of aneurysm of extrahepatic portal vein associated with recurring cholestasis is described. The diagnosis was performed via echography and abdominal TAC and confirmed by portal venography. There was no evidence of hepatopathy or portal hypertension. Possibly, the displacement of the biliary tract the portal vein is a contributing factor to recurring cholestasis in the present case.

Aneurysm↗
PubMed1994

A randomized trial of mitomycin/ifosfamide/cisplatin preoperative chemotherapy plus surgery versus surgery alone in stage IIIA non-small cell lung cancer.

The efficacy of surgery or radiotherapy as conventional treatment for stage IIIA non-small cell lung cancer (NSCLC) is limited. Recent studies have pointed out that preoperative chemotherapy may improve survival. To reconcile the two approaches, we undertook a multidisciplinary randomized trial to examine the possible synergism between preoperative chemotherapy and surgery in improved survival. Stage IIIA NSCLC patients were randomly assigned to receive either three preoperative courses of mitomycin/ifosfamide/cisplatin chemotherapy and surgery or surgery alone. The median survival was significantly greater in the chemotherapy plus surgery group than in the surgery group (26 months v 8 months; P < .001). However, the prognostic value of the mutated K-ras gene data presented awaits the analysis of larger sample populations. Similarly, the role of high-dose cisplatin in inducing higher pathologic complete remissions has to be corroborated in future randomized trials.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Modulation of tensin and vimentin expression in chick embryo developing cartilage and cultured differentiating chondrocytes.

It has been proposed that tensin, in association with several other proteins, mediates the micro-filament-integrin link. Here we describe the isolation of clones spanning about 5 kb from the 3' end of tensin mRNA from cultured chick embryo chondrocyte and embryonic heart cDNA libraries. Tensin expression was investigated in cultured chick embryo cells. It was observed that tensin expression is dependent upon substrate adhesion and it is turned off after 7 days of suspension culture. This process is reversible. Tensin expression is also regulated during cartilage cell differentiation in vivo; at Hamburger and Hamilton stage 39-40, non-hypertrophic tibial chondrocytes express both RNA and protein while hypertrophic chondrocytes do not. In the culture system the expression of vimentin, a major component of intermediate filaments, showed an opposite behaviour since the suspension culture enhances the accumulation of both vimentin and its mRNAs. Therefore in chick embryo cultured chondrocytes and in vivo, during cartilage development, cell shape changes and/or integrin-extracellular matrix protein interactions may be involved in the regulation of these two genes coding for cytoskeletal proteins.

Amino Acid Sequence↗