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F Penault-Llorca

Publications and source records attributed to F Penault-Llorca.

At least 37 records · Page 2Linked to original sources
PubMed2002

[Principal therapeutic uses of monoclonal antibodies in oncology].

In the past few years, new agents based on monoclonal antibodies have been developed in Oncology. Indeed in some case tumor cells express antigenic targets at higher levels than normal cells. There are 2 main types of monoclonal antibodies that can be either conjugated to cytotoxic drugs or radio-active compounds or be non-conjugated. Among the last category, some are currently used in the treatment of patients, including 2 monoclonal antibodies targeting receptors with tyrosine kinase activity (HER2: Herceptin (DCI: trastuzumab), EGFr: Erbitux (DCI: cetuximab). A third monoclonal antibody is commonly used in cancer treatment, which targets CD20, a transmembrane marker of B lymphoma (MabThera (DCI: rituximab). Both Herceptin and MabThera have been associated with improved survival in patients with breast carcinoma and lymphoma, respectively. New promising agents are under investigation such anti EGFr in colon and head and neck carcinoma or new compounds such as anti-VEGF. These examples outline the importance of the recent progress in selectively targeting tumor antigen and the potential impact of these approaches in Oncology.

Antibodies, Monoclonal↗
PubMed2001

WNT pathway and mammary carcinogenesis: loss of expression of candidate tumor suppressor gene SFRP1 in most invasive carcinomas except of the medullary type.

Secreted Frizzled-related protein 1 (SFRP1) encodes a member of a protein family that contains a cysteine-rich domain similar to the WNT-binding site of Frizzled receptors and regulates the WNT pathway. The WNT pathway is frequently altered in human cancers. We have defined the pattern of SFRP1 mRNA expression in the progression of breast cancer. We show that SFRP1 is expressed in the epithelial component of normal breast, in the in situ component of ductal carcinomas and is lost in more than 80% of invasive breast carcinomas except the medullary type. Loss of SFRP1 expression is correlated with the presence of hormonal receptors. Conversely, the maintenance of SFRP1 in carcinomas is correlated with the presence of lymphoplasmocytic stroma. No significant association was observed between SFRP1 status and the level of apoptosis in tumoral cells.

Adult↗
PubMed2001

[Uterine sarcoma in patients receiving tamoxifen therapy. Apropos of 2 cases].

INTRODUCTION: Tamoxifen--a non steroidal triphenylethyl compound--in addition to having antiestrogenic properties may provoke weak estrogenic effects, the well known "paradoxical effects" on the female genital tractus. Concern has been raised about prolonged tamoxifen treatment and subsequent occurrence of endometrial adenocarcinoma; subsequent attention has been drawn through high risk histologic subtypes including poorly differentiated patterns and uterine sarcomas. EXEGESIS: We report two cases of uterine sarcoma arising in postmenopausal women taking tamoxifen, 20 mg daily during 38 and 42 months, for breast carcinoma: one leiomyosarcoma and one endometrial stromal sarcoma; both cases were asymptomatic and detected by pelvic sonography. CONCLUSION: Further studies will be required to establish if there is a relationship between long term tamoxifen exposure and highly aggressive types of cancer of the uterine corpus exhibiting adverse histologic features such as uterine sarcomas. There is no consensus regarding uterine surveillance of women receiving tamoxifen. We advocate an annual gynecologic examination plus imaging by means of transvaginal ultrasonography.

Aged↗
PubMed2001

Ductal carcinoma in situ of the breast results of conservative and radical treatments in 716 patients.

Until now, less than 5% of the patients with breast ductal carcinoma in situ (DCIS) have been enrolled in clinical trials. Consequently, we have analysed the results of "current practice" among 716 women treated in eight French Cancer Centres from 1985 to 1992: 441 cases (61.6%) corresponded to impalpable lesions, 92 had a clinical size of less than or equal to 2 cm and 70 from 2 to 5 cm; in 113 cases, the size was unspecified. Median age was 53.2 years (range: 21-87 years). 145 patients underwent mastectomy (RS) and 571 conservative surgery (CS) without (136) or with (435) radiotherapy (CS+RT). The mean histological tumour sizes in these three groups were 25.6, 8.2, 14.8 mm, respectively (P<0.0001). After a 91-month median follow-up, local recurrence (LR) rates were 2.1, 30.1 and 13.8% in the RS, CS and CS +RT groups, respectively (P=0.001); LR were invasive in 59 and 60% in the CS and CS+RT groups, respectively. In these groups, the 8-year LR rates were 31.3 and 13.9%, respectively (P=0.0001). Nodal recurrence occurred in 3.7 and 1.8% in the CS and CS+RT groups. Metastases rates were 1.4, 4.4 and 1.4% in the RS, CS and CS+RT groups. Among the 60 cases of invasive LR, in CS and CS+RT groups 19% developed metastases. After multivariate analysis, we did not identify any significant LR risk factor in the CS group, whereas young age (<40 years) and incomplete excision were significant in the CS+RT group (P=0.012 and P=0.02, respectively).

Adult↗
PubMed2001

Interleukin-6 overexpression as a marker of malignancy in human gliomas.

OBJECT: Glioblastomas multiforme (GBMs) grow rapidly and are highly resistant to treatment compared with other glioma types and grades. Consequently, it is of major interest to identify markers of aggressiveness in these tumors that could represent new therapeutic targets. Interleukin (IL)-6 is frequently produced in gliomas and, given its manifold properties, could be considered as a candidate marker. Expression of IL-6 may be involved in cell growth, resistance to chemotherapy and radiotherapy (via an antiapoptotic pathway), and angiogenesis. This study was conducted to test this hypotheses and to evaluate the suitability of IL-6 as a target in the treatment of GBMs. METHODS: The authors studied the relationship between the level of IL-6 gene expression as assessed using semiquantitative reverse transcription-polymerase chain reaction and by determining various histological types and grades in a series of 59 gliomas. It was found that GBMs displayed a significantly higher level of IL-6 expression than other types of glioma (p < 0.001). Immunohistochemical analysis revealed that IL-6 was produced mainly by malignant cells and a few vascular endothelial cells. CONCLUSIONS: It can be inferred from these findings that IL-6 gene expression is related to glioma aggressiveness and that IL-6 may play a central role in GBM behavior. Interleukin-6, therefore, could be considered as a new potential target in the treatment of GBMs.

Aged↗
PubMed2001

[Molecular abnormalities in epithelial ovarian tumors: present and future].

Ovarian cancer is the fourth most common cancer in women. Its pronostic is dreadful and, in spite of numerous studies, the steps of ovarian carcinogenesis are unclear. Histologically, three sub-types of ovarian tumors (benign, borderline and invasive) are distinguished, suggesting the existence of a continuum. However, as each sub-type presents its own biologic characteristics, the hypothesis of the progression of a pre-neoplastic precursor (benign or borderline tumor) into an invasive tumor is still open to discussion. Numerous molecular biological studies have been conducted on ovarian tumors, with the aims of identifying their molecular abnormalities and better understanding the process of ovarian carcinogenesis. Synthesis of the published data (concerning oncogene amplification and/or surexpression, loss of heterozygosity, tumor suppressor gene inactivation, microsatellite instability) shows that there are numerous abnormalities, confirming the heterogeneity and the complexity of these tumors. Hence, it remains very difficult to draw a scheme of ovarian carcinogenesis. Nevertheless, in a near future the new technology of laser microdissection may improve the quality of the results and the study of early ovarian lesions. Indeed, with this technique, it becomes possible to isolate well-defined and homogeneous cell populations and to study small or architecturally complex (surface lesions) tumors. In the next years, the results obtained may allow the identification of early events of the ovarian carcinogenesis and the development of diagnostic and therapeutic tools.

DNA, Neoplasm↗
PubMed2000

Endometrial histopathology in 700 patients treated with tamoxifen for breast cancer.

OBJECTIVE: The aim of this study was the evaluation of endometrial histopathologic findings from 700 patients treated with tamoxifen (Tx) for breast cancer from two medical centers (United States and France). METHODS: A retrospective review of data including histologic slides from 134 hysterectomies and 566 endometrial biopsies from Tx-treated patients who presented with abnormal vaginal bleeding and/or abnormal sonograms was performed. Analysis of histologic characteristics included inactive/atrophic and functional endometria, endometrial polyps, hyperplasia and metaplasia, and endometrial cancer. Duration of Tx therapy was recorded when available, and its correlation with endometrial pathology was assessed. RESULTS: The only statistically significant difference between the data from the United States and France was the number of hysterectomies, which was almost double in France (27% vs 13.7%). Nonpathologic endometria made up 61.14% (inactive/atrophic 46%, functional 15.14%). Pathologic changes were found in 39.86% cases, of which polyps were 23.14%, glandular hyperplasia 8%, and metaplasia 3%; endometrial cancer made up 4.71% (33 cases). Nine cancers were well-differentiated endometrioid adenocarcinomas, and 24 were moderately or poorly differentiated, of which 13 had nonendometrioid components (serous, clear cell, MMMT). Fifteen cancers were found in endometrial polyps; 12 were invasive to the myometrium and 4 to blood vessels. The weight of the uteri exceeded 300 g in 15 cases, with 4 exceeding 900 g. The average age of all patients was 60.91 years and of the cancer patients alone it was 69.26 years. The shortest average duration of Tx therapy (2.5 years) was found in patients with inactive/atrophic endometria and the longest (6.8 years) in patients with endometrial cancer. Patients with endometrial polyps and cancer presented more often with abnormal vaginal bleeding than those with inactive/atrophic endometrium. CONCLUSIONS: Most Tx-treated patients had no pathologic endometrial changes. Endometrial polyps, hyperplasia, and metaplasia, consistent with an estrogen-agonist effect of Tx, were found in roughly one-third of all patients. The endometrial cancers were often high-grade and invasive tumors. Patients with endometrial pathology were more often symptomatic than patients with inactive/atrophic endometria.

Adult↗
PubMed2000

Structural and numerical aberrations of chromosome 22 in a case of follicular variant of papillary thyroid carcinoma revealed by conventional and molecular cytogenetics.

This study reports a case of papillary carcinoma with vesicular components showing multiclonal aberrations of chromosome 22 as revealed by RHG-banding cytogenetics and by fluorescence in situ hybridization (FISH; whole chromosome 22 and BCR-ABL-specific locus probes, multi-FISH). Four clones with chromosome 22 changes as the sole abnormality were seen. The main abnormal clone lacked the whole chromosome 22. A del(22)(q11) was observed in a second group of cells. The third clone had an idic(22). Finally, FISH revealed a fourth abnormal cell population with a der(17)t(?17;22). Some of these chromosome 22 alterations have been described in other solid tumors such as meningiomas and neurinomas, suggesting a common genetic pathway of tumor progression occurring in a multistep process. Chromosome 22 changes do not seem to be involved in pure papillary thyroid tumors and therefore could be related to the maintenance of a follicular-type histological pattern.

Adult↗
PubMed2000

Antitumoral effect of interleukin-12-secreting fibroblasts in a mouse model of ovarian cancer: implications for the use of ovarian cancer biopsy-derived fibroblasts as a vehicle for regional gene therapy.

Fibroblasts can easily be cultured from human solid ovarian tumor biopsies and are readily transfected using retroviral vectors. To test the feasibility of using these cells as a vehicle for regional, intraperitoneal (i.p.) ovarian cancer gene therapy, we first examined the behavior of murine fibroblasts transduced with the neoR marker gene and injected i.p. in syngeneic mice. We found that these fibroblasts were not invasive and formed clusters preferentially attached to the pancreatic and hepatic mesentery, where they survived for at least 30 days and continued to express neoR. We subsequently assessed the effect of regional delivery of murine interleukin-12 (mIL-12)-secreting fibroblasts in a syngeneic immunocompetent mouse model of ovarian cancer (ID8). ID8 ovarian tumor cells were injected i.p. into one flank. Our results show a survival of 88% at 120 days postinjection of animals treated with mIL-12-secreting fibroblasts i.p. in the other flank on the same day as injection of tumor cells. At that time, all animals coinoculated with ID8 cells and unmodified fibroblasts had been or needed to be culled because of advanced neoplastic disease (P < 10(-5), log-rank test). Furthermore, animals treated with mIL-12-secreting fibroblasts had a statistically significant decrease in tumor burden, as measured by diaphragm weight, relative to mock-treated groups (P = .0032, H-test). Our histological data show evidence for both immunological and anti-angiogenic mechanisms being implicated in this antitumoral effect. In addition, no signs of IL-12-induced toxicity were observed in any of the tissue sections analyzed. Taken together, our findings suggest that ovarian tumor biopsy-derived fibroblasts are a safe and efficacious vehicle for i.p. delivery of IL-12 as a regional secondary treatment for minimal residual disease of ovarian cancer.

Animals↗
PubMed2000

[Assessment of different histoprognosis grading systems for primary ovarian cancer: 100 patients given the same treatment for primary ovarian adenocarcinoma].

BACKGROUND: Numerous grading systems have been proposed for invasive ovarian epithelial carcinoma. But, conflicting reports have been published addressing the value of grade as an independent prognostic factor. DESIGN: The present study investigated the consistency, reproducibility and prognostic value of four different grading systems in a series of 100 homogeneously treated (cytoreductive surgery & platinum based chemotherapy) patient. All the slides were reviewed in a double-blind manner by 3 pathologists, typed according to the WHO and graded. Multivariate assessment of survival time was performed with the Cox model. RESULTS: Population parameters - mean age: 60 years, - stage (FIGO) III & IV 85% - survival: 5 years OS: stage III & IV=22,5%. No significant difference for survival was observed when the patients were classified with any of the 4 grades evaluated. Prognostic factors: age<60 (p<0,001), optimal surgery (p<0,01), n+(p<0,02), necrosis>50% (p<0,04), mitotic count<15MF/10HPF (p<0,03) and vascular invasion (p<0,03). Those 3 parameters were assigned to a new highly relevant grade. At multivariate analysis, it was significantly associated with DFS and OS (p<0,01). CONCLUSION: Our grade is simple, useful for all histologic types, non subjective and reproducible. Further studies are warranted to confirm its clinical utility.

Adenocarcinoma↗
PubMed1999

[Intravascular leiomyomatosis of uterine origin. a case of pseudo-metastatic cavo-cardial thrombus].

BACKGROUND: Leiomyomatosis is a benign smooth muscle tumor which can provoke serious complications in case of intracaval or intracardiac extension. CASE REPORT: A 61-year-old woman had undergone hysterectomy at the age of 45 years for a hemorrhagic fibroma. She underwent surgery for infiltrative breast cancer 3 months before hospitalization and was taking tamoxifen 30 mg/day. In the cancer context, the diagnosis of cavo-cardiac metastatic thrombus was proposed but not confirmed at pathology. The diagnosis of uterine tissue intravascular leiomyomatosis was established on the basis of pathology findings and immunohistochemistry results. DISCUSSION: Five other cases of leiomyomatosis after hysterectomy have been reported in the literature.

Breast Neoplasms↗
PubMed1999

O(6)-methylguanine-DNA methyltransferase gene (MGMT) expression in human glioblastomas in relation to patient characteristics and p53 accumulation.

Repair of cytotoxic DNA damage by O(6)-methylguanine-DNA methyltransferase (MGMT) is a potentially important factor of chemoresistance to chloroethylnitrosoureas (CENUs), commonly used in the treatment of glioblastoma multiforme (GBM). The value of p53 as a prognostic factor in GBMs remains unclear, but a possible relationship between MGMT gene expression and p53 has been suggested. To further examine these GBM characteristics in vivo, we assessed MGMT gene expression using semi-quantitative RT-PCR and p53 alteration by immuno-histochemistry on a series of 39 GBMs. MGMT gene expression was inversely correlated with age (p < 0.03), consistent with the results of others. Interestingly, tumors from male patients had higher MGMT mRNA amounts than tumors from female patients (p < 0.03). No prognostic implication was observed either for MGMT gene expression or for p53 accumulation. However, MGMT gene expression was significantly lower in p53-altered GBM, regardless of the percentage of positive cells (p < 0.01). Our observation suggests that in human glial tumors, a low level of MGMT gene expression might promote p53 alteration, probably via mutation of its gene. Int. J. Cancer (Pred. Oncol.) 84:416-420, 1999.

Aged↗
PubMed1999

Association of angiogenesis and poor prognosis in node-positive patients receiving anthracycline-based adjuvant chemotherapy.

UNLABELLED: Tumoral angiogenesis has been described as associated with poor prognosis in breast cancer, particularly for node negative breast cancer. The purpose of this study was to evaluate the influence of angiogenesis in node-positive breast cancer and particularly its potential impact on adjuvant chemotherapy. PATIENTS AND METHODS: One hundred and thirty-five node-positive breast cancer patients who received anthracycline or derivative based adjuvant chemotherapy were selected from the data base of the Institut Paoli Calmettes. Angiogenesis was evaluated using CD31 antibody. Other prognosis variables studied were: hormonal status, tumor size, hormonal receptors, Elston and Ellis grade, and number of involved lymph nodes. RESULTS: In multivariate analysis, a high level of angiogenesis was independently associated with a diminution of survival (p = 0.007), and of metastasis-free survival (p = 0.003). Other variables associated with poor survival were progesterone receptor status (p = 0.003) and Elston's grade (p = 0.003), and with metastasis-free survival, progesterone receptor status (p = 0.018). CONCLUSION: Tumoral angiogenesis appears to be an independent prognostic factor for node-positive breast cancer, when treated with adjuvant chemotherapy. Adjuvant strategies for patients with a high level of angiogenesis should be discussed.

Adult↗
PubMed1999

[Microinvasive ductal carcinoma of the breast. Role of axillary lymph node dissection].

The role of axillary lymph node dissection for microinvasive ductal carcinoma in situ of the breast was analyzed in a series of 60 consecutive cases. Forty-four cases were subclinical mammographically-detected carcinomas revealed by the clusters of microcalcifications. Although pathologists differ in their criteria for microinvasion, the maximal size considered in this retrospective study was 2 mm. Axillary lymph node involvement was found in 3 cases (i.e. 5%) which harbored poor histologic features: comedocarcinoma subtype, high nuclear grade, and size of the ductal carcinoma in situ greater than 3 cm, requiring total mastectomy. While there is no need for axillary dissection in women with pure ductal carcinoma in situ, the management is quite different in proven microinvasion. Owing to the weakness of prognostic information given by cellular, biochemical and molecular features, instead of lymph node status, axillary dissection is still recommended in microinvasive ductal carcinoma in situ.

Adult↗