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F Janot

Publications and source records attributed to F Janot.

At least 55 records · Page 3Linked to original sources
PubMed1993

In vivo measurement of the potential doubling time by flowcytometry in oropharyngeal cancer treated by conventional radiotherapy.

PURPOSE: Experimental and clinical studies suggest that the pre-treatment potential doubling time could be predictive of tumor control in patients treated by conventional radiotherapy and could help to identify the rapidly growing tumors for which accelerated radiotherapy is required. METHODS AND MATERIALS: To test this hypothesis, we studied prospectively 48 patients with a squamous cell carcinoma of the oropharynx and treated by conventional radiotherapy (70 Gy/7 weeks). The duration of S phase, the labeling index and the potential doubling time were obtained by flowcytometry measurements of a tumor biopsy obtained after injection of 200 mg bromodeoxyuridine to the patient. RESULTS: Three parameters were significantly associated with an increased risk of relapse namely the tumors size (T4; p < 0.01), the nodal status (> or = N2; p < 0.05) and the site of the primary within the oropharynx (p = 0.08). The S phase, labeling index, DNA index and potential doubling time were not significantly associated with an increased risk of relapse. However when considering only the T2 subgroup of patients, high labeling indexes and short potential doubling time were associated with an increased risk of relapse: the mean pre-treatment potential doubling time of the tumors which relapsed was 3.21 versus 5.5 days when there was no evidence of local relapse (p < 0.05). The mean labeling index for the group of tumors associated with a tumor recurrence was 11.7% compared to 7.3% when there was no evidence of relapse (p = 0.02). CONCLUSION: Factors other than proliferation play a role in determining the outcome of oropharyngeal cancers treated by conventional radiotherapy. However there was a significant correlation between short potential doubling time, high labeling index and tumor recurrence in the T2 subgroup of patients. The finding of significance for potential doubling time and labeling index in the T2 subset of tumors may be a reflexion of the more homogeneous nature of these tumors with regard to prognostic variables.

Aged↗
PubMed1993

Principal xenobiotic-metabolizing enzyme systems in human head and neck squamous cell carcinoma.

To better understand drug and carcinogen metabolism pathways in head and neck squamous cell carcinoma we assayed the principal drug- and carcinogen-metabolizing enzyme systems in both tumors and their corresponding adjacent non-tumoral tissues. Cytochromes P450 (1A1/A2, 2B1/B2, 2C8-10, 2E1, 3A4), epoxide hydrolase and glutathione S-transferases (GST-alpha, GST-mu, GST-pi) were assayed by immunoblotting. GST activity, total glutathione, UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase and sulfatase, were determined by spectral assays. Results showed the absence of all probed cytochromes P450 in tumors and non-tumoral tissues, including P450 1A1/1A2 known to be involved in tobacco-related carcinogenesis. No statistical difference was noted between tumors and adjacent non-tumoral tissues for most enzymes studied (GST-alpha, GST-mu, GST-pi, GST activity, UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase and sulfatase). However, total glutathione concentrations were significantly higher (P < 0.05) in tumors (47 +/- 20 nmol/mg protein) than in non-tumoral tissues (19 +/- 9). On the contrary, epoxide hydrolase was significantly less expressed in tumors (18 +/- 9 micrograms/mg protein) compared to corresponding non-tumoral tissues (37 +/- 9). These data provide new information concerning human head and neck cancer biology that could possibly have clinical implications.

Carcinoma, Squamous Cell↗
PubMed1993

Keratins 6, 13 and 19. Differential expression in squamous cell carcinoma of the head and neck.

One hundred forty-one head and neck squamous cell carcinomas were analyzed for keratin (K) 6, 13 and 19. Staining was evaluated by light microscopy (with or without grading) and image analyzer and expressed as a percentage of positive versus all tumor surface (PSA). Both techniques rendered strongly correlated results. Strong expression was noted in 108 carcinomas (76.1%) for K6, in 18 (12.7%) for K19 and in 21 (14.8%) for K13 (P = .001). One hundred thirty-six (96%) tumors were positive for K6, and their PSA ranged from 0.6% to 48.8%; K19, 48 cases (0.2-44%); K13, 59 (0.2-38.1%). Expression of K6 was related to differentiation. K19 was expressed mainly in moderately and poorly differentiated tumors, and K13 was manifest more in well-differentiated carcinomas or in keratinized areas of less-differentiated ones. Nineteen (13.38%) tumors were positive for both K13 and K19. K19 thus was related to tumor progression and K13 to differentiation. There was no correlation with tumor site or TNM category.

Adult↗
PubMed1993

[Screening of principal enzymes involved in the metabolism of anticancer drugs in human and murine colonic tumors].

Since drug-metabolizing enzymes may influence the toxic response of tissues or organs to drugs, we studied their expression in human and colon tumor tissues, in an attempt to find new targets for chemotherapy and also to explain the intrinsic drug-insensitivity of most colon tumors to anticancer drugs. In the present work, we compared human colorectal tumors and peritumoral tissues to a mouse colorectal tumor (Co38) and normal murine colon with regard to their main drug-metabolizing enzyme systems. We investigated cytochromes P-450 (1A1/1A2, 2B1/B2, 2C, 2E1, 3A) and epoxide hydrolase (EH) by immunoblotting. Total glutathione (GSH) and the activities of the following enzymes: total GST, selenium-independent glutathione peroxidase (GPX), 1,2-dichloro-4-nitrobenzene-GST (DCNB-GST), ethacrynic acid-GST (EA-GST), UDP-glucuronosyltransferase 1 (UDPGT), beta-glucuronidase (beta G), sulfotransferase (ST) and sulfatase (S) were investigated by fluorometric and spectrophotometric assays. Results obtained by immunoblotting showed that mouse colon tumor Co38 did not express any of the probed cytochromes P-450, whereas human tumors showed the presence of cytochrome P-450 3A. EH was not expressed in either mouse colon tumor Co38 or normal mouse colon, whereas it was expressed in human peritumoral and tumoral colon tissues at similar levels. GPX and EA-GST were detected in all tumoral and non tumoral tissues of both species. DCNB-GST was expressed in all murine tissues investigated, but was not found in human tissues. For human peritumoral and tumoral colorectal tissues there was no significant difference between GST isoenzymes levels, whereas mouse colon tumor Co38 had a lower expression of DCNB-GST and EA-GST compared to normal mouse colon. No significant difference was observed between human tumors and peritumoral tissues for total GST, UDPGT1, beta G, ST and S activities. For murine colon tissues, the conjugation pathways (total GST, UDPGT1 and ST) were lower in Co38, whereas the opposite was observed for the hydrolytic enzymes (beta G and S). In conclusion, despite similarities between human and murine colon tumors, mouse colon tumor Co38 appears different from human colon tumors for many drug-metabolizing enzyme systems. These interspecies differences may have implications with regard to drug screening methodologies and preclinical evaluation of candidate anticancer drugs useful in the chemotherapy of human colorectal tumors.

Aged↗
PubMed1992

Comparison of mouse and human colon tumors with regard to phase I and phase II drug-metabolizing enzyme systems.

Since human colorectal tumors are insensitive to most chemotherapeutic agents, there is a need for the discovery of new drugs that would show activity against this disease. In an attempt to better appreciate the relevance of a widely used mouse colon tumor (colon adenocarcinoma Co38) as a screening model for human colorectal tumors, we compared the main phase I and phase II drug-metabolizing enzyme systems in both tumoral and nontumoral colon tissues. The following enzymes were assayed by Western blot: cytochromes P-450 (1A1/A2, 2B1/B2, 2C, 2E1, and 3A), epoxide hydrolase, and glutathione-S-transferases (GST-alpha, -mu, and -pi). The activities of the following enzymes or cofactors were determined by spectrophotometric or fluorometric assays: total cytochrome P-450, 1-chloro-2,4-dinitrobenzene-GST, selenium-independent glutathione peroxidase, 3,4-dichloronitrobenzene-GST, ethacrynic acid-GST, total glutathione, epoxide hydrolase, UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, and sulfatase. Results obtained by Western blot showed that mouse colon adenocarcinoma Co38 did not express any of the probed cytochromes P-450, whereas human colorectal tumors expressed only low levels of cytochrome P-450 3A. GST-alpha and GST-pi were detected in all tumoral and nontumoral tissues of both species. The neutral GST-mu was expressed in all murine tissues investigated and was found to be polymorphic in human tissues. For human peritumoral and tumoral colorectal tissues there was no significant difference between GST isoenzyme levels, whereas mouse colon adenocarcinoma Co38 had a lower expression of GST-mu and GST-pi, compared to normal mouse colon. Enzymatic activities for glutathione peroxidase, 3,4-dichloronitrobenzene-GST, and ethacrynic acid-GST confirmed the Western blot results for GST-alpha, GST-mu, and GST-pi, respectively. Total GSH levels were similar between murine and human tumors but were 3-fold higher in human tumors than in peritumoral tissues, whereas they were 7-fold lower in mouse colon tumor Co38, compared to normal mouse colon. Epoxide hydrolase was not expressed in either mouse colon adenocarcinoma Co38 or normal mouse colon tissues, whereas it was expressed in human colon peritumoral and tumoral tissues at similar levels. No significant difference was observed between human tumors and peritumoral tissues for UDP-glucuronosyltransferase, beta-glucuronidase, sulfotransferase, and sulfatase. For murine colon tissues, the conjugation pathways (UDP-glucuronosyltransferase and sulfotransferase) were lower in colon adenocarcinoma Co38, whereas the converse was observed for the corresponding hydrolytic enzymes (beta-glucuronidase and sulfatase).(ABSTRACT TRUNCATED AT 400 WORDS)

Adenocarcinoma↗
PubMed1991

[Measurement of the kinetics of cell proliferation of cancer of the oropharynx in vivo by the incorporation of bromodeoxyuridine and flow cytometry].

Forty-six tumors from patients with oropharyngeal carcinoma were analysed by flow cytometry after injection of bromodeoxyuridine (Budr) for the labelling index, the duration of S phase and the potential doubling time (Tpot). The results show large variations in Tpot (from 2.6 to 16.7 days) among these tumors from the same site and with the same histology. The variations in Tpot were not significantly related to TNM status and differentiation grade. However, aneuploid tumors had statistically significant shorter Tpot. The predictive value of Tpot regarding the response to radiotherapy is currently under investigation.

Bromodeoxyuridine↗
PubMed1991

[Combined approach to malignant tumors of the ethmoid and other paranasal sinuses. Principles and results].

The authors present their experience concerning combined transfacial and neurosurgical procedures in the treatment of carcinomas of the ethmoid sinuses. 109 ethmoid-spheno-orbital tumors were treated at our department from 1982 to 1990: 85 were located into the ethmoidal and/or sphenoidal sinuses; 78 of these were malignant. Among the 65 ethmoidal carcinomas which were operated through a combined route, 48 underwent an induction chemotherapy and 19 a post-operative radiotherapy. The surgical technique is detailed, mostly the intra-cranial approach and the reconstruction of the cranial basis. Clinical results, and particularly the actuarial survival rates are discussed. The 5-year actuarial survival rate is 40% for all first hand ethmoidal adenocarcinomas. The figure reaches 52% for the patients without intra-cranial extension. At last, the 5-year actuarial survival rate is 100% for patients having a complete clinical response to induction chemotherapy.

Actuarial Analysis↗
PubMed1991

[Free forearm flap used in the reconstruction of the cervico-cephalic region. 43 cases].

The free neurovascular antebrachial transplant was described by Yang-Guofan in 1978. In 1981, we brought the description of this free transplant to Europe. Forty-three antebrachial grafts were made to reconstruct the cervicocephalic extremity. We had various indications: floor of the mouth and base of the tongue: 18 cases, facial structures: 7 cases, posterior wall of the pharynx: 9 cases, rescue surgery for esophagoplasty: 6 cases, mandible: 2 cases (using a bone rod taken from the radius), internal aspect of the cheek: 1 case. All grafts were revascularized. In 41 cases, the indications were carcinological, the last 2 cases being benign lesions. The early postoperative mortality included 1 case, not related to the nature of the operation (neoplasm). There was no failure of free transplants. Surveillance was ensured every half-hour during 12 hours, then every 3 hours. Discriminating sensation was recovered in 39 of 43 cases. Mandibular bone reconstructions were knit at the 3rd month. The main disadvantage of removing this graft is esthetic, as it leaves a considerable scar on the forearm. The free antebrachial transplant provides an effective solution to the reconstructions of the cervicocephalic extremity, when a narrow, thin, supple, reinnervated, compound transplant is needed.

Adolescent↗
PubMed1991

[Mandibular reconstruction using free vascularized fibula transplant].

Free revascularized fibular transplants have been used in surgery for the reconstruction of long bones since 1973. The reconstruction of the mandible using a free fibular transplant has been published in 1989 only by Hidalgo. The mandible and the fibula have little in common, except for their length and a similar structure in section. The anatomical study of the free osteofasciocutaneous fibular graft included 20 fresh subjects. The vascularization of the fasciocutaneous plate is either grouped or, more frequently, tiered (2/3 of cases). The technique to remove this graft is specified. Four clinical cases are reported, including three cases of neoplasm of the floor of the mouth invading the mandible, and one case of traumatic amputation of the lower part of the face. A free composed transplant taken from the fibula has been used in all four cases. The postoperative period was normal, and the grafts were completely successful. The main indications of free transplants made of fibular bone are: extensive (more than 8 cm) or compound losses of bony substance from the mandible. The richly vascularized transplant take from the fibula is very sophisticated and performant. The length of bone that can be removed is 25 cm; the bone may be osteotomized in 2 to 4 fragments retaining their vitality. Other tissular structures such as the skin, fascia, muscle, are removed with the bone. The independence in space is threefold and regards the bone, the teguments and the vascular pedicle. The microsurgical qualities of the vascular pedicle are considerable. These free transplants improve the quality of survival (endosseous implants in one case). The morphological, functional and esthetic result is good as a rule.

Adult↗
PubMed1989

Myomucosal shunt following total laryngectomy: a report of 31 cases.

An original technique of voice rehabilitation following total laryngectomy based on the concept of a myomuscosal unit was originally described by Strome. Thirty-one cases of myomucosal shunts (MMS) are analyzed in the present report. The 14 initial cases failed because of a lack clinical and surgical experience and insufficient selection of the patients. Among the last 17 cases, 1 was lost to follow-up, 1 had an insufficient follow-up, and 2 patients refused to speak with the MMS instead of a patent shunt; 5 of the remaining patients had voices evaluated as excellent, 7 had voices interpreted as good and only 1 patient had a voice evaluated as poor. Aspiration was not a problem. Eleven patients were found to stenose their shunt, but fistula were recalibrated successfully. The MMs can be used safely in oncological surgery and only 1 of 31 deaths in our total experience was due to a local recurrence. These findings show that the MMS is a reliable procedure for voice restoration following total laryngectomy; a prosthesis is not required and there are currently no oncological limits to the procedure. However, a very close follow-up of the patients is required after surgery.

Adult↗
PubMed1989

[ORL cancer in the child. Histologic and topographic distribution. Therapeutic indications (apropos of 380 IGR cases 1975-1987)].

Three-hundred and eighty cases of head and neck cancers in children, observed in the Pediatric Department of the Institut Gustave Roussy over a 12-year period are reported. The authors study the clinical presentation of these cancers (primary site and histological distribution) and consider the major prognostic factors. A brief reminder is then given of the therapeutic indications for the main tumors observed.

Child↗
PubMed1989

[Radiotherapy of cancer limited to the vocal cords].

197 patients, with an early glottic cancer, were heated with radiotherapy at the Institute Gustave Roussy, between 1970 and 1983. Radiation was delivered up to a dose of 65 Gy over 6 1/2 weeks on a small area centered on the glottic region. All patients had previously undergone direct laryngoscopy and showed T1 stage tumours (175 T1a and 22 T1b) although in 32 cases there was a suspicion of very limited involvement of the ventricle or sub-glottis. 5 year survival for the overall population was 77.5%. 38 local recurrences were observed, 1/4 of these occurring after 3 years. For the overall population, local control at 5 years was 85.7%. Suspicion of supra or sub-glottic involvement and the presence of impaired mobility of the larynx were shown to be important prognostic factors. Local control at 5 years was 90% for "true T1" cases. Few complications were observed and the functional results of irradiation were judged to be excellent.

Adult↗
PubMed1988

[Inoperable cancers of the upper respiratory and digestive tracts. Value of chemotherapy: 185 cases].

A series of 185 squamous cell carcinomas of the head and neck was retrospectively analyzed. Induction chemotherapy was systematically administered. The overall tumour response rate was 38 per cent, and 39 tumours (22.4 per cent) became resectable after chemotherapy. The survival of complete responders was statistically higher than that of non or partial responders. Complete responders treated either by radiation therapy or surgery had similar survivals. Surgery improved the prognosis and reduced the rate of local and regional failures in non responders, including poor responders (less than 50 per cent).

Carcinoma, Squamous Cell↗
PubMed1988

[Chemotherapy and partial surgery in epithelioma of the pharyngo-larynx].

On the basis of a series of 185 patients, the authors evaluate the results of the therapeutic sequence chemotherapy-partial surgery in carcinomas of the pharyngolarynx. The action of chemotherapy is confirmed (80% clinical responses greater than 50%, 55% residual tumours or in complete histological regression). The therapeutic sequence chemotherapy-surgery gave 25% local failures and 1% lymph node failures. The development of the therapeutic strategy in carcinomas of the pharyngolarynx is considered in relation to the action of current modalities of chemotherapy.

Actuarial Analysis↗