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T Petit

Publications and source records attributed to T Petit.

At least 55 records · Page 3Linked to original sources
PubMed2001

Chemotherapy response of breast cancer depends on HER-2 status and anthracycline dose intensity in the neoadjuvant setting.

We evaluated the predictive value of a tumor's HER-2 status for chemotherapy response in the neoadjuvant setting and the effect of anthracycline dose intensity on this predictive value. HER-2 status was evaluated by immunochemistry on microbiopsy before neoadjuvant chemotherapy (monoclonal antibody CB-11; Novocastra) in 39 patients (group A) treated with FEC50 (500 mg/m(2) 5-fluorouracil, 50 mg/m(2) epirubicin, and 500 mg/m(2) cyclophosphamide) and 40 patients (group B) treated with FEC100 (500 mg/m(2) 5-fluorouracil, 100 mg/m(2) epirubicin, and 500 mg/m(2) cyclophosphamide). All tumors were stage II or noninflammatory stage III adenocarcinoma. Overall response rate (OR) was evaluated through ultrasound and mammographic measurements. Pathological complete response was evaluated by tumor excision and axillary node resection after six cycles of chemotherapy. Patient and tumor characteristics (age, tumor size, clinical nodal status, SBR grade, hormonal receptor status, and HER-2 expression) were similar in the two groups. In univariate analyses, anthracycline dose was the only factor predictive of response (OR = 61.5% with FEC50; OR = 82.5% with FEC100; P = 0.038). When anthracycline dose was correlated with HER-2 status, an OR of 73.9% was demonstrated in HER-2- tumors (tumors without HER-2 overexpression), and an OR of 12.5% was demonstrated in HER-2+ tumors (tumors with HER-2 with overexpression) in group A. In group B, an OR of 69.5% was demonstrated in HER-2- tumors, and an OR of 100% was demonstrated in HER-2+ tumors. There was no difference in OR for HER-2- tumors treated with FEC50 or FEC100 (P = 0.74). On the other hand, erbB-2+ tumors treated with FEC100 had a significantly better OR than HER-2+ tumors treated with FEC50 (P = 0.0003). In a multivariate analysis, the most powerful predictive factor of OR was a conditional variable associating anthracycline dose with HER-2 status. Low-dose anthracycline and HER-2+ predicted a poor OR, low- or high-dose anthracycline and HER-2- predicted an intermediate OR, and high-dose anthracycline and HER-2+ predicted a high OR. Our results merit additional studies, given the possibility for choosing anthracycline dose according to a tumor's HER-2 status.

Adenocarcinoma↗
PubMed2000

An interlaboratory comparison of physiological and genetic properties of four Saccharomyces cerevisiae strains.

To select a Saccharomyces cerevisiae reference strain amenable to experimental techniques used in (molecular) genetic, physiological and biochemical engineering research, a variety of properties were studied in four diploid, prototrophic laboratory strains. The following parameters were investigated: 1) maximum specific growth rate in shake-flask cultures; 2) biomass yields on glucose during growth on defined media in batch cultures and steady-state chemostat cultures under controlled conditions with respect to pH and dissolved oxygen concentration; 3) the critical specific growth rate above which aerobic fermentation becomes apparent in glucose-limited accelerostat cultures; 4) sporulation and mating efficiency; and 5) transformation efficiency via the lithium-acetate, bicine, and electroporation methods. On the basis of physiological as well as genetic properties, strains from the CEN.PK family were selected as a platform for cell-factory research on the stoichiometry and kinetics of growth and product formation.

Journal Article↗
PubMed2000

The alm1+ gene from Schizosaccharomyces pombe encodes a coiled-coil protein that associates with the medial region during mitosis.

We have isolated a cDNA that encodes a 142 kDa protein by immunoscreening of a Schizosaccharomyces pombe expression library with a new antibody, mAb8, that reveals spindle poles and equatorial ring-like structures in several organisms. This cDNA encodes a putative protein which we termed Alm (for abnormal long morphology). The protein is predicted to be a coiled-coil protein, containing a central alpha-helical domain flanked by non-helical terminal domains. Immunofluorescence analysis showed that Alm1 is localized in the medial region of the cell from anaphase to the end of cytokinesis. Cells carrying an alm1::ura4+ disruption are viable and exhibit an elongated morphology. Homozygous alm1::ura4+ diploids sporulated normally but the spores did not germinate. Spores that have inherited the disruption allele from a heterozygous alm1+/ alm1::ura4+ diploid germinated but generated smaller colonies. We propose that Alm1 participates in the structural organization of the medial region in S. pombe.

Amino Acid Sequence↗
PubMed2000

Thoracic pheochromocytoma revealed by ventricular tachycardia. Clinical case and review of the literature.

A case of thoracic extra-adrenal pheochromocytoma was observed in a 13-year-old girl. The initial clinical symptoms consisted of her being unwell after effort over a period of 3 years. The diagnosis was suggested after a recorded episode of paroxysmal ventricular tachycardia with concomitant hypertension, which reproduced the characteristic symptoms. Biochemical analysis confirmed hypersecretion of catecholamines and morphological examinations showed the presence of an isolated left median thoracic tumor. One year after surgical excision, the patient remained completely asymptomatic, in spite of resuming intense sporting activity. The diagnosis of ectopic pheochromocytoma should be considered as a possible etiology of cardiac rhythm disturbances or hypertension in children. Thorough biochemical and radiological examination including MIBG radioisotope scanning should be carried out systematically before surgical excision; pheochromocytomas in children are frequently extra-adrenal (30%), multifocal (50%) or associated with multiple endocrine neoplasms (NEM).

Adolescent↗
PubMed2000

Carbohydrate and energy-yielding metabolism in non-conventional yeasts.

Sugars are excellent carbon sources for all yeasts. Since a vast amount of information is available on the components of the pathways of sugar utilization in Saccharomyces cerevisiae it has been tacitly assumed that other yeasts use sugars in the same way. However, although the pathways of sugar utilization follow the same theme in all yeasts, important biochemical and genetic variations on it exist. Basically, in most non-conventional yeasts, in contrast to S. cerevisiae, respiration in the presence of oxygen is prominent for the use of sugars. This review provides comparative information on the different steps of the fundamental pathways of sugar utilization in non-conventional yeasts: glycolysis, fermentation, tricarboxylic acid cycle, pentose phosphate pathway and respiration. We consider also gluconeogenesis and, briefly, catabolite repression. We have centered our attention in the genera Kluyveromyces, Candida, Pichia, Yarrowia and Schizosaccharomyces, although occasional reference to other genera is made. The review shows that basic knowledge is missing on many components of these pathways and also that studies on regulation of critical steps are scarce. Information on these points would be important to generate genetically engineered yeast strains for certain industrial uses.

Carbohydrate Metabolism↗
PubMed2000

Hexokinase regulates kinetics of glucose transport and expression of genes encoding hexose transporters in Saccharomyces cerevisiae.

Glucose transport kinetics and mRNA levels of different glucose transporters were determined in Saccharomyces cerevisiae strains expressing different sugar kinases. During exponential growth on glucose, a hxk2 null strain exhibited high-affinity hexose transport associated with an elevated transcription of the genes HXT2 and HXT7, encoding high-affinity transporters, and a diminished expression of the HXT1 and HXT3 genes, encoding low-affinity transporters. Deletion of HXT7 revealed that the high-affinity component is mostly due to HXT7; however, a previously unidentified very-high-affinity component (K(m) = 0.19 mM) appeared to be due to other factors. Expression of genes encoding hexokinases from Schizosaccharomyces pombe or Yarrowia lipolytica in a hxk1 hxk2 glk1 strain prevented derepression of the high-affinity transport system at high concentrations of glucose.

Biological Transport↗
PubMed2000

Simian homologues of human gamma-2 and betaherpesviruses in mandrill and drill monkeys.

Recent serological and molecular surveys of different primate species allowed the characterization of several Kaposi's sarcoma-associated herpesvirus (KSHV) homologues in macaques, African green monkeys, chimpanzees, and gorillas. Identification of these new primate rhadinoviruses revealed the existence of two distinct genogroups, called RV1 and RV2. Using a degenerate consensus primer PCR method for the herpesvirus DNA polymerase gene, the presence of KSHV homologues has been investigated in two semi-free-ranging colonies of eight drill (Mandrillus leucophaeus), five mandrill (Mandrillus sphinx), and two hybrid (Mandrillus leucophaeus-Mandrillus sphinx) monkeys, living in Cameroon and Gabon, Central Africa. This search revealed the existence of not only two distinct KSHV homologues, each one belonging to one of the two rhadinovirus genogroups, but also of two new betaherpesvirus sequences, one being close to cytomegaloviruses and the other being related to human herpesviruses 6 and 7 (HHV-6 and -7). The latter viruses are the first simian HHV-6 and -7 homologues identified to date. These data show that mandrill and drill monkeys are the hosts of at least four novel distinct herpesviruses. Moreover, mandrills, like macaques and African green monkeys, harbor also two distinct gamma-2 herpesviruses, thus strongly suggesting that a second gamma-2 herpesvirus, belonging to the RV2 genogroup, may exist in humans.

Animals↗
PubMed2000

[Mathieu's urethroplasty in surgery for hypospadia postoperative complications].

UNLABELLED: The aim of the study was to report the results of meatal based flap urethroplasty called Mathieu urethroplasty, in failed preliminary surgery for hypospadias. PATIENTS AND METHODS: Fourteen boys aged three to 14 years underwent surgery using a meatal-based flap urethroplasty for the correction of prior hypospadia repair complications. The secondary procedure was performed for glandular or coronal urethrocutaneous fistula in ten cases, completely failed urethroplasty in three cases, and for severe meatal retraction in one case. The surgical technique was the same as that used for the primary Mathieu procedures. RESULTS: Only one meatal retraction occurred; the other 13 cases had satisfactory procedure of hypospadias repair failures. Despite the scar skin used for secondary meatal based flap, good results can be achieved specially in two favorite indications: juxta coronal urethrocutaneous fistula and meatal retraction.

Adolescent↗
PubMed2000

[Anterior hypospadias: Duplay or Mathieu?].

OBJECTIVE: The Mathieu urethroplasty is considered to be the reference operation for the treatment of anterior hypospadias. The vertical incision of the urethral groove, described by Snodgrass, has extended the field of indications for urethroplasty by tubularisation of the urethral plate (Duplay principle), by allowing it to be applied in almost every case of anterior hypospadias, The objective of this study was to compare results of Mathieu urethroplasty and Duplay urethroplasty for the treatment of anterior hypospadias. MATERIALS AND METHODS: 50 Mathieu urethroplasties and 50 Duplay urethroplasties were performed by the same operator over the same period (1996 to 1999). All urethral sutures were performed by inverted running sutures. Urine drainage was ensured by Foley catheter for 48 hours. For Duplay operations, the urethral plate was incised longitudinally in 17 out of 50 cases. Foreskin reconstruction was performed 41 out of 100 cases. RESULTS: The follow-up is 6 months to 4 years. Three children (6%) in each group had to be reoperated because of urethral complications (fistula, meatal stricture, urethroplasty dehiscence). CONCLUSION: Our results confirm those published in the literature. Duplay and Mathieu urethroplasties provide equivalent results in terms of the urethra. The appearance of the urinary meatus appears to be more satisfactory after Duplay urethroplasty. The Snodgrass modification allows tubularisation of the urethral plate to be performed even when it is narrow. Cover of the urethroplasty by a foreskin subcutaneous connective tissue pedicled flap reduces the fistula rate of Duplay urethroplasty to the same value as that observed after Mathieu urethroplasty, although it classically used to be higher.

Child↗
PubMed2000

[Germ-line mutations of the BRCA1 gene in northeastern France].

Thirty-seven breast/ovarian or breast-only cancer families selected on a regional basis have been analyzed for mutations at BRCA1. By combining direct sequence analysis and protein truncation test, mutations were detected in 14 families (38%). We found seven different mutations, two of which have not been described before. Mutations at BRCA1 were present in 60% of breast/ovarian and 32% of breast-only cancer families. Mutations were frequent in families with at least one breast cancer case before age 40 (44%) and/or one bilateral breast cancer case (54%). Two mutations, namely 3600del11 and G1710X, are frequent in the population native from northeastern France. Oriented BRCA1 analysis should facilitate carrier detection in breast and/or ovarian cancer families stemming from this French area.

Adult↗
PubMed1999

Molecular cloning and characterization of the gene HXK1 encoding the hexokinase from Yarrowia lipolytica.

We have cloned the gene HXK1 from the dimorphic yeast Yarrowia lipolytica that encodes the unique hexokinase of this yeast. The gene has an intron located 39 base pairs after the A of the first ATG. The putative protein contains a sequence of 40 amino acids which is absent from other known hexokinase sequences. Y. lipolytica strains devoid of hexokinase grew in glucose slower than wild-type. This growth was due to the existence of a glucokinase. The hexokinase from Y. lipolytica substituted effectively for hexokinase II from S. cerevisiae in catabolite repression of invertase. The hexokinases from Schizosaccharomyces pombe or Kluyveromyces lactis were much less effective in this role. The K(m) for glucose and fructose of hexokinase was 0.38 mM and 3.56 mM, respectively. The K(m) of glucokinase for glucose was 0.17 mM. While the hexokinase was strongly inhibited by trehalose-6-phosphate (K(i)=3.6 microM), glucokinase was not affected by this compound.

Amino Acid Sequence↗
PubMed1999

Activity of SCH 66336, a tricyclic farnesyltransferase inhibitor, against human tumor colony-forming units.

BACKGROUND: The ras gene product regulates transduction of growth-proliferative signals from the membrane to the nucleus. Mutationally-activated Ras is the oncogene most frequently found in human tumors. In order to perform its function in cell signaling, Ras must be farnesylated on the CAAX motif present on the carboxyl terminus of the ras protein. This reaction is catalysed by farnesyl protein transferase. In the present study, SCH 66336, an orally bioavailable nonpeptide tricyclic farnesyltransferase inhibitor, was tested against a large variety of human tumors to define its preclinical activity profile, utilizing the human tumor cloning assay. MATERIALS AND METHODS: A soft agar cloning assay was used to determine the in vitro effects of SCH 66336 against primary human tumor specimens taken directly from patients. A total of 70 evaluable specimens were exposed to SCH 66336 for 14-day continuous exposure at concentrations ranging from 0.1 to 2.5 microM. In vitro responses were defined as an inhibition > or = 50% of human tumor colony forming units at a given concentration. RESULTS: There was a positive relationship between concentration and response to SCH 66336. With the highest concentration (2.5 microM), response was demonstrated in 50% (three of six) of breast tumors, 40% (6 of 15) of ovarian tumors, and 38% (5 of 13) of non-small-cell lung tumor colony forming units. Among the 69 specimens tested at the concentration of 2.5 microM, SCH 66336 had activity in 27% of tumor specimens that were resistant to doxorubicin, 38% of tumor specimens resistant to cisplatin, 33% of tumor specimens resistant to paclitaxel, and 27% of tumor specimens resistant to etoposide. CONCLUSIONS: The broad spectrum of soft agar growth inhibition by SCH 66336 in the human tumor cloning assay, and its efficacy at physiologically relevant concentrations in animal models, suggest that SCH 66336 may deserve future clinical trials in patients with ovarian, breast and non-small-cell lung cancer.

Alkyl and Aryl Transferases↗
PubMed1999

A phase I study of docetaxel and 5-fluorouracil in patients with advanced solid malignancies.

PURPOSE: This study was undertaken to evaluate the feasibility of administering docetaxel (Taxotere; Rhône-Poulenc-Rorer) as a one-hour intravenous (i.v.) infusion on day 1 combined with 5-fluorouracil (5-FU) as a bolus i.v. injection for five (days 1-5) or three (days 1-3) consecutive days every four weeks. PATIENTS AND METHODS: Thirty-seven patients with advanced solid malignancies were treated with 115 total courses involving seven dose levels of the two regimens of docetaxel and 5-FU (docetaxel/5-FU [mg/m2]/mg/m2/d]). In an effort to reduce fluid retention and hypersensitivity phenomena related to docetaxel, patients received premedication with dexamethasone 8 mg orally twice daily for three consecutive days beginning 24 hours before treatment. RESULTS: Severe (grade 4) neutropenia lasting longer than seven days with or without fever and/or severe mucositis, precluded further dose escalation above docetaxel 60 mg/m2 on day 1 and 5-FU 300 mg/m2/day administered on days 1-5 every four weeks. The rates of these toxic effects were also unacceptably high above docetaxel 60 mg/m2 on day 1 and 5-FU 300 mg/m2/day administered on days 1-3 every four weeks. Nine patients experienced various manifestations of fluid-retention that were potentially related to study drugs. However, neither treatment delay nor discontinuation of treatment was required. Nausea, vomiting, diarrhea, and fatigue, were mild to modest in severity and occurred infrequently (< 10% of courses). Two patients with metastatic breast cancer experienced complete responses and a partial response occurred in a patient with metastatic non-small-cell lung cancer. CONCLUSION: Based on the results of this study, the regimen of docetaxel 60 mg/m2 on day 1 followed by 5-FU 300 mg/m2/d i.v. for three or five days every four weeks is well tolerated and these doses are recommended for further evaluations. The feasibility of administering docetaxel 60 mg/m2 followed by 5-FU 300 mg/m2 for three or five days every four weeks and the preliminary antitumor activity noted indicate that further disease-directed studies of docetaxel and 5-FU are warranted in patients with relevant solid malignancies.

Adult↗
PubMed1999

Elimination of extrachromosomal c-myc genes by hydroxyurea induces apoptosis.

Hydroxyurea (HU) increases extrachromosomal DNA elimination in tumor cell lines. The c-myc oncogene is one of the many relevant amplified genes contained within the extrachromosomal DNA compartment. Spontaneous loss of amplified copies of c-myc induces terminal differentiation and apoptosis in the human HL-60 leukemia cell lines. In the present study, we evaluate HU's ability to induce apoptosis by eliminating extrachromosomally located c-myc oncogene in human tumor cell lines. The consequences of eliminating extrachromosomal DNA by HU were explored in two different cell lines using the TdT assay and acridine orange/ethidium bromide labeling. COLO 320 clone 3 and COLO 320 clone 21 cell lines contain the same number of amplified copies of c-myc oncogene, but located respectively on extrachromosomal DNA, and intrachromosomally in homogeneously staining regions. HU induced apoptosis in the COLO 320 clone 3 cell line by a time and concentration dependent mechanism but could not induce apoptosis in the COLO 320 clone 21 cell line. These results suggested that HU-induced apoptosis in COLO 320 cell lines depends on elimination of extrachromosomal amplified copies of the c-myc oncogene. The ability of HU to eliminate extrachromosomally amplified copies of the c-myc oncogene and to induce apoptosis should be considered when targeting malignancies with amplification of the c-myc oncogene in an extrachromosomal site.

Journal Article↗
PubMed1999

Does the endoscopic incision of ureteroceles reduce the indications for partial nephrectomy?

OBJECTIVE: To determine whether the endoscopic incision of ureteroceles reduces the indications for partial nephrectomy. PATIENTS AND METHODS: Between 1987 and 1996, endoscopic incision was used as the first-line treatment of 18 children (13 boys, five girls, aged 8 days to 6 months) with a duplex-system ureterocele diagnosed antenatally (15) or in the first weeks of life during the course of a urinary infection (three). Of the 19 ureteroceles (one bilateral), four were intravesical and 15 ectopic, according to the American Academy of Paediatrics classification. Vesico-ureteric reflux into the inferior pole of the kidney was present in 10 children, seven of whom had an ectopic ureterocele. A functioning upper pole was detected by intravenous pyelography (IVP) in half the intravesical and in a third of the ectopic ureteroceles. RESULTS: Endoscopic incision resulted in decompression and reduction of dilatation in 16 cases; three with inferior pole reflux resolved on control cystography, whilst in seven with an ectopic ureterocele, reflux into the upper urinary tract was induced by endoscopic incision. In three children with an ectopic ureterocele, renal function had improved at 3 months, as assessed by IVP. Endoscopic incision was the only treatment for half the intravesical and six of 15 ectopic ureteroceles. Overall, nephrectomy was required in four of 18 patients (three partial nephrectomies for persistent dilatation and one total nephrectomy). Five nonfunctioning, undilated upper poles with no reflux were left in place. Nine vesico-ureteric reimplantations for persistent or induced reflux were carried out using the Cohen technique. CONCLUSION: Endoscopic incision can allow the deferral of nephrectomy, facilitate lower urinary tract reconstruction and reduce the indications for partial nephrectomy, if it is accepted that a nonfunctioning, undilated renal pole with no reflux can safely be left in place.

Electrocoagulation↗
PubMed1999

Activity of MKT 077, a rhodacyanine dye, against human tumor colony-forming units.

MKT 077 is related to rhodamine 123 dye and demonstrates preferential accumulation in the mitochondria of cancer cells compared to normal cells. This difference in retention between cancer and normal cells led to the finding that MKT 077 selectively inhibits the growth of cancer cells in vitro. To define the preclinical activity profile of MKT 077, the compound was tested in vivo against a large variety of human tumors utilizing the human tumor-cloning assay. MKT 077 was studied using a sequential 2 h exposure separated by 24 h (2-24-2 h) and a 24 h exposure at final concentrations of 0.1, 0.2, 1.0, 2.0, 10.0 and 20.0 microg/ml. MKT 077 was also studied using continuous exposure at final concentrations of 0.1, 1.0 and 10 microg/ml. A decrease in tumor colony formation was considered significant if survival of colonies treated with MKT 077 was 50% or less compared to untreated controls. A total of 149 specimens was treated with MKT 077 with 51, 58 and 34 evaluable specimens with the 2-24-2 h, the 24 h and the continuous exposure, respectively. The results of the present study suggest a positive relationship between concentration and response. No relationship between exposure schedule and activity was observed. Inhibitory effects were obtained against multiple tumor types. High cytotoxic activity was obtained against breast, ovary, endometrial, colon and non-small cell lung cancer with concentrations of 2 microg/ml or above. In conclusion, the broad spectrum of cytotoxicity of MKT 077 in the human tumor-cloning assay and the unique mechanism of action of MKT 077 encourage additional preclinical and clinical studies with this compound and other rhodacyanine dyes.

Antineoplastic Agents↗