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Biomedical subjects

M Bolla

Publications and source records attributed to M Bolla.

At least 91 records · Page 5Linked to original sources
PubMed1996

Release of leukotriene A4 versus leukotriene B4 from human polymorphonuclear leukocytes.

The reactive intermediate formed by 5-lipoxygenase metabolism of arachidonic acid, leukotriene A4, is known to be released from cells and subsequently taken up by other cells for biochemical processing. The objective of this study was to determine the relative amount of leukotriene A4 synthesized by human polymorphonuclear leukocytes (PMNL) that is available for transcellular biosynthetic processes. This was accomplished by diluting cell suspensions and measuring the relative amounts of enzymatic versus nonenzymatic leukotriene A4-derived metabolites after challenge with the Ca2+ ionophore A23187. Nonenzymatic leukotriene A4-derived metabolites were used as a quantitative index of the amount of leukotriene A4 released into the extracellular milieu. The results obtained demonstrated that in human PMNL, the relative amounts of nonenzymatic versus enzymatic leukotriene A4-derived metabolites increased with decreasing cell concentrations. After a 20-fold dilution of PMNL in cell preparations, a doubling in the amount of nonenzymatic leukotriene A4-derived metabolites was observed following challenge (from 53.9 +/- 1.3 to 110.4 +/- 8.9 pmol/10(6) PMNL, p < 0.01). Reduction of possible cell-cell interactions by dilution suggested that over 50% of leukotriene A4 synthesized is released from the PMNL. These data provide evidence that, in human PMNL preparations, transfer of leukotriene A4 to neighboring PMNL is taking place, resulting in additional formation of leukotriene B4 and its omega-oxidized metabolites 20-hydroxy- and 20-carboxy-leukotriene B4. Neutrophil reuptake of extracellular leukotriene A4 leads to an underestimation of the fraction of leukotriene A4 that is in fact available for transcellular metabolism when tight cell-cell interactions occur, such as during PMNL adhesion to the microvascular endothelium and diapedesis.

Biological Transport↗
PubMed1996

Protein tyrosine kinase activity in 350 T1/T2, N0/N1 breast cancer. Preliminary results.

Protein tyrosine kinases (PTKs) are a family of enzymes sharing a highly conserved catalytic domain which phosphorylates substrate proteins on tyrosine residues. PTKs play a major role in the transduction of the mitogenic signal and are involved in the control of cell proliferation, differentiation, and transformation processes. PTKs can be subdivided into two major types: membrane associated PTKs consisting essentially of growth factor receptors (receptor tyrosine kinases or RTKs) and cytosolic PTKs involved in the intracellular transduction of mitogenic and differentiation signals. From January 1988 to January 1992, PTK activity was assayed in cytosolic fractions prepared from 350 T1-T2, N0-N1 M0, breast carcinomas. Enzymatic activity was measured using phosphate transfer from [32P]-ATP to poly-Glu-Tyr as an artificial substrate. According to our previously reported pilot study, we chose a cut-off value of 12 pmol 32P incorporated min-1 mg-1 protein, corresponding to the median value. We found positive PTK levels (> or = 12 pmol/min/mg) to be correlated with a loss of differentiation according to Scarff-Bloom grade (p < 0.001), negative PR (p = 0.03) and ER status (p = 0.04). With a median follow-up of 30 months (0-82), patients with a positive PTK level presented a smaller 3-year disease free survival than in the PTK negative group of patients (p = 0.07). In Cox multivariate analysis including pT, pN, Scarff-Bloom grade, PR and ER, PTK activity does not emerge as a significant prognostic factor.

Adult↗
PubMed1996

Feasibility of retroperitoneal pelvic lymph node exploration in cervical carcinoma. Assessment of morbidity in 33 cases treated by combined radio-surgery or definitive radiotherapy.

BACKGROUND AND PURPOSE: Laparoscopic modalities by selective biopsies permit a better assessment of the pelvic lymph nodes status than imaging procedures in cervix carcinoma. They could enable the radiation oncologist to adapt the target volume of external irradiation, provided the feasibility of such procedures is good and the toxicity reduced as much as possible. MATERIAL AND METHODS: From June 1980 to May 1993, 52 women with a mean age of 49, underwent a retroperitoneal pelvic lymph node laparoscopic procedure for cervix carcinoma classified according to FIGO as stages IA2 (14), IB (12), IIA (6), IIB (14), IIIB (3) and IVA (3). Two techniques were used: retroperitoneoscopy (RPS) in 16 cases, and a panoramic retroperitoneal pelviscopy (PRPP) in 36 cases. RESULTS: Intra-operative and post-surgical morbidity were equivalent in the two procedures. Among the 33 patients who had external irradiation, one Grade 3 urinary late morbidity (3%) due to an overtreatment was observed; no Grade 3/4 morbidity of the gastro-intestinal tract, no lymphoedema of the lower extremities, no parietal tumor cells implantation were noticed. CONCLUSIONS: These procedures can be used safely to better know the prognosis and to define the pelvic lymph node planning target volume and its radiation management with accuracy.

Adult↗
PubMed1996

Prognostic value of quantitative cytometry in a series of 415 T1T2/N0N1/M0 breast cancer patients--preliminary results.

Identifying prognostic markers in local regional breast carcinomas remains an important challenge today. DNA content obtained by flow cytometry, has been found to be of prognostic value; results with other methods remain less clear. This report describes DNA image cytometry patterns which are assessed with respect to disease-free survival. From June 1982 to December 1992, 415 patients under 75 years of age, without any previous or synchronous carcinoma, suffering from an invasive breast cancer classified as T1 (52.8%), T2 (47.2%), N0 (65.1%) N1 (34.9%), MO according to clinical TNM staging, were enrolled in this study. The median age was 53 (28-75) and 58.8% of the patients were premenopausal; 85.3% underwent a breast conservative procedure and 14.7% a modified radical mastectomy followed by postoperative irradiation. Histological axillary lymph node status, Scarff-Bloom grade and/or cytological grade and, oestrogen receptor content were used in decision-making for adjuvant treatment: hormonotherapy (48%) or chemotherapy (18.8%). Imprints were taken from the macroscopically visible lesion at the time of surgery, and a Feulgen staining was carried out on air dried smears to be analysed using the Samba 200 cell image processor (Alcatel TITN, France). Five parameters were systematically assessed: proliferation index; DNA histogram, integrated optical density, DNA malignancy grade, ploidy balance. With a median follow-up of 36 months (0-105), proliferation index (P = 0.0008), DNA histogram (P = 0.0017), integrated optical density (IOD) (P = 0.018) and DNA malignancy grade (P = 0.017) had a significant prognostic value on disease-free survival estimated by the Kaplan-Meier method. When these parameters were included in a Cox proportional regression hazards model, PR (P = 0.01), Scarff-Bloom histological grading (P = 0.02), axillary clearance (P = 0.04) were significant; however, in the same model, taking into account the axillary lymph node histological status, IOD was significant for pN- patients (P = 0.03), and proliferation index (P = 0.03) was significant for pN+. Such results need to be updated with a longer median follow-up, but they suggest that the mean DNA content, as measured by the integrated optical density (IOD), should be considered when deciding on medical adjuvant treatment with respect to patients with a negative axillary clearance.

Adult↗
PubMed1996

[Simultaneous screening of cancers of the breast, cervix, colon and rectum. The Isère experience].

The mass screening program for cancer in the Isere department offers women between 50 and 69 years a medical consultation and three tests: mammography for breast cancer screening, Pap smear for cervical cancer screening, and hemoccult for colorectal cancer. During the first round, 29,570 women took part in the program, 21% had a mammography, 20% Pap smears and 25% a hemoccult. In breast cancer screening, the rate for further examination was 11.9%, the breast cancer detection rate was 5.4 per 1,000 women screened and the detection rate of invasive tumor < or = 10 mm: 2.0 per 1,000. In cervical cancer screening, the rate of abnormal examinations was 1.2%. The cervical cancer detection rate was 1.5 per 1,000. The rate of positive hemoccult was 2.7% and the rate of colorectal cancers and polyps 10 mm or larger was 2.7 per 1000. Results of screening are satisfying, but compliance rate is too low. Acceptance rate must be examined in following rounds.

Aged↗
PubMed1996

[Prognostic value of quantitative DNA analysis, expressed in integrated optical density, in a series of 415 T1-T2, N0N1, M0 UICC breast cancers].

From June 1982 to December 1992, 415 patients less than 75 years of age, without any previous or synchronous carcinoma, suffering from an invasive breast cancer classified as T1 (52.8%), T2 (47.2%), NO (65.1%) N1(34.9%), MO according to clinical TNM staging, were enrolled in this study. The median age was 53 (28-75), and 58.8% of the patients were menopaused; 85.3% underwent a breast conservative procedure and 14.7% a modified radical mastectomy followed by postoperative irradiation. Histological axillary lymph node status, Scarff-Bloom grade and/or cytological grade, estradiol receptor content, were used to set up medical adjuvant treatment: hormonotherapy (52%) or chemotherapy (18.8%). Imprints were taken from the macroscopically visible lesion at the time of surgery, and a Feulgen staining was done on air dried smears to be analyzed using the Samba 200 cell image processor (Alcatel TITN, France). Five parameters were systematically assessed: proliferation index, DNA histogram, integrated optical density, DNA malignancy grade, and policy balance. With a median follow-up of 36 months (0-105), proliferation index (P = 0.0008), DNA histogram (P = 0.0017), integrated optical density (P = 0.018), DNA malignancy grade (P = 0.017) have a significant prognostic value on disease free survival estimated by the Kaplan-Meir method. When these parameters were included in a Cox proportional regression hazards model, Scarff-Bloom histological grading (P = 0.002), positives nodes (P = 0.02), optical integrated density (P = 0.045) were significant. Such results need to be updated with a longer follow-up, but they suggest that the mean DNA content, as measured by the integrated optical density (IOD), has to be considered when deciding on medical adjuvant treatment with respect to patients with a negative axillary clearance.

Adult↗
PubMed1996

[The anticancer regional office, a screening facility in Isère].

The Isère anticancer departmental office (ODLC) created by order in June 1981, assumes the responsibility of screening. Since 1991 its action has focused on breast cancer mass screening in women aged 50 to 69 years, as well as cervix, colon and rectum carcinomas for the same age group. The board of directors includes politicians and representatives of administrative services from, DASS, DISS, CHU, cancer registry, centre d'études nucléaires, University Joseph Fourier, the French Medical Association, medical trade-unions, CPAM, and charitable organizations. Its budget for 1995 was 3.6 million FF, subsidized up to 90% by the regional council. After being invited by CPAM or private insurances, each woman is submitted to a consultation with a general practitioner or gynecologist who fill in the questionnaire, perform a clinical examination (including PAP smears), prescribe a mammography and give a hemoccult test. This mass screening is free of charge thanks to FNPIES, CPAM and private insurances. ODLC seems to be the most qualified structure of coordination and follow-up to take charge of a departmental mass screening.

Aged↗
PubMed1996

[Survey of the use of contention shells in Centre-Rhône-Alpes area].

Contention shells are frequently used in radiotherapy. They allow improvements in the reproducibility of treatments and take part in quality assurance. The aim of our survey is to establish how centers use contention masks. Ninety-five percent of the centers questioned use contention masks. The fixation device is in most cases made of Plexiglas. The masks are always made of thermoplastics materials with low modeling temperature. They are made just before simulation or scanner by a radiographer. The surface dose problem can be overcome by two different techniques. One consists in the stretching of the material to reduce the density. The other consists of cutting out the mask where the irradiation fields are projected. Whatever the technique, there is a loss of rigidity of the mask, which means the immobilization is not so effective. Despite drawbacks, contention masks have an important role in the quality insurance in radiotherapy.

Biomechanical Phenomena↗
PubMed1996

[Fast growing IB-IIB cancer of the uterine cervix. Apropos of 20 cases].

Twenty cases of fast growing cancer of the uterine cervix (14 IB, three IIA, three IIB FIGO), the definition of which is specified, have been reviewed and compared to a cohort of 160 cases not having this feature, to assess their outcomes. In regard to fast growing carcinomas, the median age was 41 (25-50) years and the median follow-up 22 months (8-213) as compared to 54 years (27-79) and 80 months (5-199) for the reference cohort. The comparison of the two cohorts shows only a difference of breakdown which concerns the pelvic lymph nodes status (P < 0.05, chi 2). Thirteen deaths are reported in the fast growing series instead of 54 in the other series. The 5-year overall survival is respectively 34% (13-55) versus 74% (68-82), the loco-regional free survival 58% (33-84) versus 85% (79-81) (P < 0.001), the 5-year metastasis free survival 61% (38-84) versus 84% (78-90) (P = 0.004). This particular form needs a multidisciplinary approach, and the local regional treatment has to be intensified.

Adult↗
PubMed1995

Therapy program for patients with advanced stages of chronic lymphocytic leukemia. Chlorambucil, splenectomy, and total lymph node irradiation.

BACKGROUND: The clinical course of chronic lymphocytic leukemia (CLL) is variable. Staging systems define high risk groups, such as patients with Rai's Stage III and IV and Binet's stage C disease, as having a poor overall median survival. Most combination therapy programs have resulted in similar results. Chlorambucil remains the most commonly used drug, and new drugs, such as fludarabine, are promising. METHODS: Fifty-three patients with poor prognosis CLL (Stage III and IV) underwent chlorambucil treatment at a high intermittent dose. When Stage 0 was obtained, patients were considered responders and kept under surveillance. When the patients stopped responding after one or several courses of chlorambucil, further therapy was performed, including splenectomy (29 patients) and total lymph node irradiation (9 of the 29 splenectomized patients). RESULTS: The overall median survival was 60 months. Thrombocytopenia and anemia were resolved in 55% and 82% of the patients, respectively, after chlorambucil therapy and in 85% and 100%, respectively, after splenectomy. Complications occurred in 34% of the splenectomized population. Total lymph node irradiation was poorly tolerated in 66% of the patients. When this analysis was performed, 24 patients were classified as having Stage 0 disease with no disease progression for a mean of 21 months. CONCLUSIONS: Therapy programs allowing the selection of responders by the successive use of high intermittent dose chlorambucil and splenectomy may be beneficial in treating patients with advanced stage CLL. Because of its toxicity, total lymph node irradiation has no significant therapeutic effect.

Adult↗
PubMed1995

Patient setup optimization for external conformal radiotherapy.

The aim of conformal radiotherapy is to deliver precisely a specific dose of radiation to a planning target volume, concurrently radiating as little healthy tissue and organs as possible. This can be accomplished only with the accurate positioning of the patient with respect to the radiotherapy system. In this paper, we describe a system to achieve a higher overall accuracy in the delivery of a prostatic radiation boost for treatment of carcinoma of the prostate. The system is based on the use of ultrasound images for measuring the actual position of the patient's prostate just before the radiation. Since these images are registered with pretreatment computed tomography or magnetic resonance imaging, the position and orientation of the planning target volume are computed with respect to the radiotherapy system and can be corrected as needed. This system is under clinical evaluation.

Computer Simulation↗
PubMed1995

EORTC guidelines for writing protocols for clinical trials of radiotherapy.

The concept of a Master Protocol for phase III studies was raised at the Steering Committee of the EORTC Radiotherapy Group, in order to make the work of the study coordinators easier, when writing protocols and to give them more homogeneity. The Master Protocol defines and clarifies in a logical order the different steps which must be taken when designing a randomized trial--from the rationale to the references. It pays particular attention to eligibility criteria, volumes of interest defined in agreement with ICRU Report 50 (gross tumor volume, clinical target volume, planning target volume and organs at risk), simulation procedure, treatment technique, normal tissue sparing, dose computation, equipment, dose specification (also in agreement with ICRU Report 50). Last but not least, the different procedures of quality assurance for protocols and patients are also defined (site visits, dummy run procedure, in vivo dosimetry, individual case review) to allow working plans to be made in advance. We are aware that this work is not exhaustive, but hope that the contents will be of help to those who are writing a protocol.

Clinical Trials as Topic↗
PubMed1995

Quality assurance of the EORTC radiotherapy trial 22863 for prostatic cancer: the dummy run.

The results of a dummy run involving nine centers participating in a study comparing radiotherapy alone with radiotherapy plus hormone therapy in patients with high metastatic risk prostatic cancer (EORTC protocol 22863) show that, in all centers but one, patients are treated in the same way. However, they have also indicated that protocol compliance could be improved by a better assessment of the target volume, by taking into account of the use of protective shields and of variations in radiological density, by determining beam position on a large number of slices, and by the use of CT scan images for treatment planning.

Clinical Protocols↗