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Biomedical subjects

I Marcillac

Publications and source records attributed to I Marcillac.

7 recordsLinked to original sources
PubMed2000

Phase I-II study of high dose epirubicin plus cisplatin in unresectable non-small-cell lung cancer: searching for the maximal tolerated dose.

The purpose of this study was to search for the maximal tolerated dose of cisplatin in the cisplatin plus high-dose epirubicin combination for patients with non-small-cell lung cancer. The following range of cisplatin dosages were tested in a phase I study: 75, 90, 105, and 120 mg/m2 in combination with epirubicin 120 mg/m2 every 3 weeks. Eligibility consisted of previously untreated stage IIIb or IV non-small-cell lung cancers, Eastern Cooperative Oncology Group Performance Status less than or equal to 2, age less than or equal to 70 years, measurable disease, adequate blood counts, chemistry, cardiac function, and no brain metastasis. The maximal tolerated dose was defined as the dose level of cisplatin for which two of three patients or three of six patients developed one or more limiting toxicities during the first course of therapy. Afterward, the maximal tolerated dose of cisplatin was adopted in a subsequent phase II study. Three centers enrolled 42 patients: 18 in phase I and 24 in phase II. The maximal tolerated dose was almost reached at the last dose level (i.e., 120 mg/m2). Taking into account the total duration of the treatment, the real dose intensity for patients treated at the fourth dose level (120 mg/m2) did not differ from that of the third dose level (105 mg/m2). The latter dosage was therefore considered as the maximal tolerated one. In the subsequent phase II study, the median number of cycles received per patient was three (range: one to eight). Fifty percent required a dose reduction of either epirubicin, cisplatin, or both. The main toxicity was neutropenia, resulting in 10 episodes of febrile grade IV neutropenia requiring readmission. Other toxicities were mild to moderate. There was no toxic-related death. On intent-to-treat analysis, 10 patients (33%) achieved an objective response. Among them were three complete responders. Median survival was 8 months. We observed neither detraction nor improvement of quality of life as assessed using the European Organization for Research and Treatment of Cancer QLQ-C30-LC13. Given every 3 weeks in combination with epirubicin 120 mg/m2, the maximal tolerated cisplatin dose is 105 mg/m2. This combination yields activity in non-small-cell lung cancer.

Adult↗
PubMed1996

Antimüllerian hormone as a serum marker of granulosa cell tumorsof the ovary: comparative study with serum alpha-inhibin and estradiol.

OBJECTIVE: Our purpose was to evaluate serum antimüllerian hormone as a marker for granulosa cell tumors. STUDY DESIGN: Serum antimüllerian hormone concentrations were determined in 16 patients with an adult-type granulosa cell tumor; in female patients with ovarian adenocarcinoma, benign ovarian cysts, or extraovarian cancers; and in normal premenopausal and postmenopausal women. Serum antimüllerian hormone, alpha-inhibin, and estradiol levels were compared in 10 patients with a granulosa cell tumor during 6 to 47 months of follow-up. RESULTS: Serum antimüllerian hormone was undetectable in normal postmenopausal women and was <5 micrograms/L in premenopausal women. Normal serum levels were found in patients with ovarian cancers or cysts or with extraovarian cancers. Levels were between 6.8 and 117.9 microg/L in eight of nine patients with a progressive granulosa cell tumor. In the remaining case antimüllerian hormone, alpha-inhibin and estradiol concentrations were normal. Serum antimüllerian hormone and alpha-inhibin levels became elevated at least 11 months before the recurrence was clinically detectable. During clinical remission serum antimullerian hormone, beta-inhibin, and estradiol were normal in most cases. CONCLUSION: Serum antimüllerian hormone is a sensitive, specific, reliable marker of adult-type granulosa cell tumors and is useful to evaluate the efficacy of treatment and to detect recurrences early.

Adolescent↗
PubMed1995

Reaction of peripheral-blood lymphocytes to the human chorionic gonadotropin beta sub-unit in patients with productive tumors.

Human chorionic gonadotropin (hCG) and its beta sub-unit (hCG beta) are secreted by trophoblast cells during pregnancy, and by tumoral cells of trophoblastic and non-trophoblastic origin. In contrast to hCG, the free hCG beta sub-unit is consistently undetectable in healthy non-pregnant subjects. With this in mind, we sought to determine whether an immune response to hCG beta can be detected in patients with bladder or germ-cell testis cancers. Peripheral-blood mononuclear cells (PBMC) from 31% of patients with hCG beta-productive bladder cancers and 33% of testis-tumor-bearing patients displayed an hCG beta-specific proliferative response, whereas no patients with non-hCG beta-productive cancers had a proliferative response. PBMC from pregnant women and healthy controls did not elicit significant reactivity. By the use of overlapping synthetic peptides, the immunogenic regions of hCG beta were delineated within the central 20-65 portion. Moreover, in 2 bladder-cancer patients with the HLA DR7, DQ2 haplotype, the T-cell response to hCG beta was focused on the hCG beta (20-47) peptide. Taken together, these results indicate that hCG beta is a tumor-associated antigen capable of inducing a cell-mediated immune response in patients with productive tumors.

Aged↗
PubMed1993

[Thrombosis and cancer].

Thrombotic episodes represent the second cause of mortality in cancer patients. These complications are more frequent with some adenocarcinomas and hematologic malignancies. The mechanisms of pathogenesis are complex inducing an unbalanced function of the antithrombotic system. According to the type of tumor and the underlying mechanism, clinical manifestations are generally severe. The diagnosis of these thromboses are essentially clinical or radiological. The treatment is based on heparinotherapy, thrombolytic agents or eventually on surgery, which is not discussed here.

Heparin↗
PubMed1992

Free human chorionic gonadotropin beta subunit in gonadal and nongonadal neoplasms.

The diagnostic value of elevated human chorionic gonadotropin (hCG) and its free alpha (hCG alpha) and beta (hCG beta) subunit serum levels as specific tumor markers for nongonadal malignancies is controversial. In the present report, different monoclonal based immunoradiometric assays specific for hCG and its free hCG alpha and hCG beta subunits have been used to reevaluate the presence of these molecules in the serum of patients with a wide variety of tumors. Serum samples from patients with newly diagnosed, persistent, or recurrent malignancies of either known (n = 717) or unknown (n = 32) primary site, healthy blood donors (n = 309), and nonmalignant disease controls (n = 86) were studied using four highly specific and sensitive monoclonal based immunoradiometric assays to hCG and its free subunits. Low level hCG elevations (less than 1000 pg/ml) were found to be common in cancer patients, normal subjects, and disease controls. However, serum levels greater than 1000 pg/ml were highly diagnostic of gonadal tumors and specifically identified nonseminomatous testicular tumors. Significant serum elevations of free hCG alpha subunit (as high as 3000 pg/ml) were found in approximately 96% of cancer patients, normal individuals, and disease controls. In contrast, free hCG beta subunit levels (greater than or equal to 100 pg/ml) were detected in 70 and 50% of patients with nonseminomatous and seminomatous testicular cancers, respectively, and in 47% of bladder, 32% of pancreatic, and 30% of cervical carcinomas. All normal subjects and disease controls had free hCG beta levels less than 100 pg/ml. Thus, the detection of the free hCG beta subunit in serum of nonpregnant subjects was highly diagnostic of malignancy in general and specifically defines a subgroup of aggressive nongonadal malignancies.

Adult↗
PubMed1992

Monoclonal antibodies to the free beta-subunit of human chorionic gonadotropin define three distinct antigenic domains and distinguish between intact and nicked molecules.

The present study was designed to characterize monoclonal antibodies (mAbs) specific for the free beta-subunit of hCG (free hCG beta), to develop two-site immunoradiometric assays (m-IRMAs) specific for free hCG beta, and to study the reactivities of various molecular forms of hCG beta in these assays. We attempted first to delineate the antigenic regions present specifically on the free hCG beta by studying the binding pattern of seven mAbs directed preferentially to hCG beta, designated FBT11, P8E, P10F, HB2, P5D, P5H, and INN-64. Competitive inhibition experiments performed by RIA demonstrated the specificity of these mAbs for the free hCG beta as noncross-reacting with the beta-subunit of human (h) LH beta. m-IRMAs were used to analyze the arrangement of epitopes on hCG beta. Experiments performed with the seven mAbs used either as capture antibodies or radiolabeled indicators confirmed the specificity of the seven mAbs for the free hCG beta, and that mAbs FBT11, P8E, and P10F bound to equine LH beta (eLH beta), but did not bind to a fragment of hCG beta called the beta-core fragment (beta CF). These antibodies defined an antigenic domain identified as A. In contrast, mAb HB2 bound neither to eLH beta (e beta) nor to beta CF and was directed to domain B (e beta negative, beta CF negative). Finally, mAbs P5D, P5H, and INN-64 bound to beta CF, but did not bind to eLH beta, and defined a third domain identified as C (e beta negative, beta CF positive). Collectively, these results demonstrate that at least six antigenic domains are present on the free hCG beta and that a limited set of amino acids was shared among these domains; domains A, B, and C are present only on the free beta-subunit, while three other domains recognized by mAbs FB19, FBT10, and 518B7 are present on both free hCG beta and hCG. Thus, most of the surface of the hCG beta appears to be antigenic and accessible to antibody binding. Three different m-IRMAs specific for free hCG beta were then constructed using either mAb FBT11 (domain A) or HB2 (domain B). The study of the reactivities of various molecular forms of hCG beta in these assays demonstrated that the recognition of hCG beta forms nicked at position 43 (beta 43), 44, and/or 51 (beta 44/51) varied between assays.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗