N-6 polyunsaturated fatty acids in human breast carcinoma phosphatidylethanolamine and early relapse.
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Adult↗
Biomedical subjects
P Bougnoux
Publications and source records attributed to P Bougnoux.
[Breast recurrence after conservative treatment of cancers of the breast: predictive factors and prognostic significance].
The prognostic significance of local relapse after conservative treatment of early stage breast cancer has been controversial. To determine the prognostic value of breast relapse occurrence and the factors predisposing to local failure, we analysed the results obtained in a series of 324 patients conservatively treated for breast invasive carcinomas of 2 cm or less. All patients were treated by tumorectomy and axillary dissection, radiation therapy, and adjuvant medical treatment in 85 of 109 patients with involved nodes. The overall 5-yr survival rate was 91.5%. The actuarial 5-yr local control rate was 91.9%. Local relapses occurred in 25 patients. In these patients, the overall 5-yr survival rate was significantly decreased as compared to that of patients without local relapse (76.9% versus 93.4%, P less than 0.001). Recurrence in the breast within 2 yr of initial treatment of severely affected the risk of metastasis occurrence as compared to later relapses (metastasis-free survival rate of 14.3% versus 63.9% at 3-yr from local relapse, P less than 0.01). Local relapse occurred more frequently in premenopausal patients, in patients with low bodymass index, and in patients with small breast size. Local control was not significantly affected by age, tumor size or node involvement. We conclude that the occurrence of a breast relapse after a local conservative treatment has a negative significance and is predictive of a high risk of distant metastasis development, especially when local relapse occurred within 2 yr of initial treatment. There is a need to determine individual factors that could allow discrimination of patients with a high probability of local relapse and subsequent metastasis.
Adult↗
Presence of PAF-acether in human breast carcinoma: relation to axillary lymph node metastasis.
PAF-acether (PAF; formerly platelet-activating factor), a potent lipid mediator of inflammation, is involved in multiple cellular functions. To evaluate the role of PAF in human cancer, we obtained specimens from patients with localized breast carcinoma and assayed them for PAF. PAF was found in almost all carcinoma, although it was not detected in most of the matched, nontumor breast tissue samples. Intratumor PAF level was elevated when axillary lymph node involvement was low. Greater axillary extension (two or more positive lymph nodes) was associated with a decreased intratumor PAF level. These findings, along with the independence of other prognostic factors, indicate that PAF is a tumor marker of axillary lymph node involvement.
Axilla↗
Carcinoma of the uterine cervix stage IB and early stage II. Prognostic value of the histological tumor regression after initial brachytherapy.
In our center limited centro pelvic invasive carcinomas of the uterine cervix (less than 4 cm) are treated with brachytherapy and surgery. With these therapeutic modalities no residual carcinoma was observed for 80% of the patients. The purpose of this study was to evaluate our results with this treatment, and to evaluate the prognostic value of the pathological status of the cervix. From 1976 to 1987 we have treated 115 patients with these modalities. Staging system used was the FIGO classification modified for Stage II (divided in early Stage II and late Stage II). Patients were Stage IB (70 cases) and early Stage II (45 cases); 60 Gy were delivered with utero vaginal brachytherapy before any treatment. Six weeks later a radical hysterectomy with pelvic lymphadenectomy was performed. Twenty-one patients with positive nodes received a pelvic radiotherapy (45 to 55 Gy). Local control rate was 97% (100% for Stage IB and 93% for early Stage II). Uncorrected 10-year actuarial survival rate was 96% for Stage IB and 80% for early Stage II patients. No treatment failure was observed for Stage IB patients. Ninety-two patients (80%) had no residual carcinoma in the cervix (group 1) and 23 patients (20%) had a residual tumor (group 2). The sterilization rate of the cervix was 87% for Stage IB tumors versus 69% for early Stage II, and was 82% for N- patients versus 68% for N+ patients. Ten year actuarial survival rate was 92% for group 1 and 78% for group 2 (p = 0, 1). Grade 3 complications rate was 6%. We conclude that brachytherapy + surgery is a safe treatment for limited centro pelvic carcinomas of the uterine cervix (especially Stage IB) and that pathological status of the cervix after brachytherapy is not a prognostic factor.
Adenocarcinoma↗
Squamous cell carcinoma of the base of the tongue: results of treatment in 115 cases.
Between 1976 and 1986, we treated 115 patients (mean age 53.8 years) with base of tongue carcinomas. The staging system used was the UICC TNM classification of 1979. Seventy per cent of the tumours were T3 or T4 and 42% had N2 or N3 lymph node. Locoregional treatment was irradiation alone (98/115) or surgery and post-operative radiotherapy (17/115). Sixty-seven patients received induction chemotherapy. Actuarial survival of the entire group at 3 and 5 years was 25 and 23%, respectively, and 3-year actuarial survival rates for T1, T2, T3 and T4 lesions were 42, 48, 20 and 17%, respectively. The local control rate at the primary site was 55% and 78% in the neck. Distant metastases occurred in 10% of patients and 8% had a second primary. Nodal status was the only other prognostic factor. The local control rate obtained with irradiation alone was not good. For limited T1 and T2 tumours, interstitial therapy or surgery should improve the local control rate.
Antineoplastic Combined Chemotherapy Protocols↗
[Carcinoma of the cervical stump. Retrospective analysis of 43 cases].
Seven to eight percent of cervix carcinomas are carcinomas of the cervical stump. The prognosis for these tumors has sometimes been considered more unfavourable than that for carcinomas on intact uterus. From 1976 to 1986 we treated 43 patients with carcinoma of the cervical stump. The mean age was 63.6 years. Staging system used was FIGO classification modified according to the criteria of Institut Gustave Roussy in Villejuif. There were 12 stage IB, 12 early stage II, 5 late stage II and 14 stage III. Twenty-four centropelvic tumors (IB and early stage II) were treated with radiotherapy and surgery, 2 with surgery alone and one with radiotherapy alone. Late stage II and stage III tumors were treated with radiotherapy alone (+ hysterectomy for two patients). Local control rate was 83% for centropelvic tumors and 53% for late stage II and stage III. Seven patients developed distant metastases. Uncorrected 5-year actuarial survival rate was 78% for centro-pelvic tumors and 46% for late stage II and stage III. Three patients developed severe complications (grade 3). Prognostic factors were: stage, nodal status and pathological status of the cervix after radiotherapy. For the same stage the results were similar to those observed for carcinomas on intact uterus treated at our institution during the same time period.
Adult↗
[Carcinoma of the cervix stages Ib, II, III. Results of treatment and prognostic factors. Retrospective analysis of 396 cases].
Between 1976 and 1986 we have treated 396 patients with carcinoma of the uterine cervix, stages Ib, II and III. The mean age was 54.2 years. The staging system used was the FIGO classification, modified according to the Institut Gustave-Roussy criteria. There were in stage Ib 117 cases, in early stage II 124 cases, in late stage II 63 cases and in stage III 92 cases. Treatment methods used were radiotherapy and surgery combined for localised pelvic lesions (stage Ib and stage II) and radiotherapy alone for those cases that were central and going out to the side wall of the pelvis (late stage II and stage III). The actuarial five-year survival rate was 91% for stage Ib, 67% for early stage II, 48% for late stage II and 28% for stage III. The main causes of failure were recurrence in the pelvis in 15% of treated areas and distant metastases in 13%. The state of the lymph nodes was another prognostic factor but the histological subtype and age were not. 7% of cases had severe complications (urinary, digestive and lymphatic).
Carcinoma↗
Specialization in membrane structure and metabolism with respect to polyunsaturated lipids.
The principal features of the hypotheses presented here are presented in a model (Figure 8). Polyunsaturated phospholipids are preferentially localized on the cytosolic leaflet of the plasma membrane and around proteins. They influence the physical state of these microenvironments and thereby help to regulate cellular functions. Losses of these species due to phospholipase attack, dietary deprivation or other pathological stimuli (such as alcohol), may lead to drastic alterations in some of these functions. The PUFA's released, including 22:6 omega 3, can be metabolised by a lipoxygenase enzyme in the brain and platelet and the products formed are biologically active.
Animals↗
Alteration in the membrane fatty acid composition of human lymphocytes and cultured transformed cells induced by interferon.
The effects of interferon (IFN) treatment on the lipid composition of human peripheral blood lymphocytes or transformed cell line cells were investigated. The major phospholipid classes of lymphocytes as analyzed by 2-dimensional TLC and quantified by phosphorous content were phosphatidylcholine (PC, 43%) and phosphatidylethanolamine (PE, 28%), along with phosphatidylserine (9%) and phosphatidylinositol (8%). The membrane-impermeant reagent, trinitrobenzenesulfonate was used to covalently label cell surface PE. Fatty acid (FA) composition, determined by gas-liquid chromatography, showed a distinct pattern in each lipid class, with a predominance of 16 and 18 carbon fatty acids (FA) in PC and PE respectively. Arachidonic acid (20:4) and, to a lesser extent, docosahexanoic acid (22:6) were predominant in PE. The degree of unsaturation in each class, expressed as the ratio between unsaturated and saturated FA (U/S), was higher in PE (1.72) than in derivatized trinitrophenyl cell surface PE (TNP-PE, 0.57) or PC (0.64). Treatment with IFN resulted in an increased U/S ratio in cell surface PE (1.10) but not in other PE species (1.46). A small increase in unsaturation (0.88) was also observed in PC. Most of the increase in TNP-PE U/S was accounted for by an increase in 20:4 and a concomitant decrease in 18:0. These alterations were observed in the absence of quantitative change in the principal phospholipid classes or in the FA composition of the total lipid extract. In K562, a transformed cell line with characteristics of the erythromyeloid lineage, PE was found to be the most saturated lipid class with a predominance of 18:0. In PC, 16:0 was most abundant. Among unsaturated FA, 18:1 predominated in all lipid classes studied. Treatment with natural IFN alpha for 30 hr generally resulted in a decrease in saturated FA and an increase in unsaturated FA, which was most marked in PE. The U/S ratio in PE was highest in K562 cells during the time of maximal cell proliferation as assessed by tritiated thymidine incorporation. TNP-PE simultaneously decreased. Daudi cells, a B-lymphoblastoid cell line, demonstrated changes in FA composition of lipids with decreased saturated and monoenoic FA after IFN treatment, whereas DIF3 (a clone selected for lack of sensitivity to IFN) showed no change. These studies document changes in membrane FA composition of lymphocytes treated with IFN and correlate IFN-induced changes in transformed cell line FA with effects on proliferation. They further show the existence of a transverse molecular species asymmetry of PE in the plasma membrane of these cells which is altered after IFN treatment.
Cell Line↗
[Complications and results of Wertheim's operation performed for the treatment of uterine cancer].
Enlarged colpohysterectomy with lymphadenectomy was performed in 199 patients for cancer of cervix (132 cases), of endometrium (67 cases), of vagina (2 cases) or of tubes (1 case) during combined radiosurgical therapy of these tumors. There was no mortality, the incidence of thrombo-embolic accidents was 3% and urinary fistula was not seen. A lumphocele developed in 7.5% of cases, this level being related to the degree of lymphatic curettage, which should involve not less than 13 glands to avoid lack of efficacy and not more than 20 glands to prevent complications, in cervical cancer. For endometrial cancer, curettage is limited to external iliac obturator glands and retrocrural nodes in young women, and is even omitted in elderly women.
Adolescent↗
Activation of the oxidative burst in human monocytes is associated with inhibition of methionine-dependent methylation of neutral lipids and phospholipids.
Chemotaxis and generation of the oxidative burst by phagocytes are among the biological functions thought to require methylation reaction(s) for their expression. The present study investigated the effect of different stimuli of the oxidative burst on lipid methylation by human elutriated monocytes as measured by methyl group incorporation from [methyl-3H]methionine into both phospholipid and neutral lipid extracts. Normal monocytes, incubated at 37 degrees C for 1 h with 2 microM methionine, incorporated 10.2-fmol/10(6) cells and 73.6-fmol/10(6) cells of methyl groups into neutral lipids and phospholipids, respectively. Stimulators of the respiratory burst, such as the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine, the tumor promoter, 12-O-tetradecanoyl phorbol-13-acetate, and the calcium ionophore, A23187, decreased the incorporation of methyl groups into both neutral lipids and phospholipids in a similar manner. Increasing the concentration of methionine in the medium reversed or attenuated the inhibition achieved at lower levels. An inverse relationship existed between the degree of methylation and the extent of stimulation of the oxidative burst, measured as superoxide anion (O-2) release. Stimulated monocytes oxidized methionine to methionine sulfoxide (which cannot act as a methyl-donor), and this was dependent on activation of the respiratory burst. Elimination of the accumulated methionine sulfoxide by replacement of the medium or by prevention of extracellular methionine oxidation by catalase did not effectively restore the normal level of methylation in stimulated cells, and the reduced methylation was not primarily related to a defective methionine uptake by stimulated monocytes. These data suggest that intracellular events related to activation of the respiratory burst are responsible for the decreased lipid methylation in stimulated cells, possibly by their leading to intracellular formation of methionine sulfoxide and by their limiting the availability of methyl-donor. This mechanism may be of potential relevance for the expression of biological functions where methionine-dependent reactions are involved.
Calcimycin↗
Identification of ubiquinone-50 as the major methylated nonpolar lipid in human monocytes. Regulation of its biosynthesis via methionine-dependent pathways and relationship to superoxide production.
Human blood monocytes incorporated the methyl group from methionine into their neutral lipids. The major methylated product was identified as ubiquinone-50 in monocytes, lymphocytes, and a variety of human tumor cell lines by several analytical procedures including TLC or high performance liquid chromatography and as ubiquinone-45 in a mouse tumor cell line. Up to three methyl groups were shown to be derived from methionine by mass spectrometry. The rate of synthesis of ubiquinone-50 by monocytes as assessed by measuring labeled methyl group incorporation was shown to be linear over a 3-h period. Degradation of ubiquinone proceeded slowly; 80% of the labeled compound persisted after 18 h. The dependence of ubiquinone-50 synthesis upon methionine concentration was established in monocytes, with an estimated apparent Km for methionine of about 20 microM. The tumor promoter, tetradecanoate phorbol acetate, a potent stimulator of superoxide anion (O2-) production in phagocytic cells, inhibited ubiquinone-50 synthesis at nanomolar concentrations in monocytes, but not in lymphocytes, under conditions where oxidation of methionine takes place. Degradation of the labeled ubiquinone was unaffected. Formylmethionylleucyl-phenylalanine, a chemoattractant peptide which stimulates O2- production in phagocytic cells, also inhibited ubiquinone-50 synthesis. The degree of inhibition by either stimulus was increased when the methionine concentration in the medium was low. These findings demonstrate that in human monocytes ubiquinone-50 biosynthesis is regulable and that methionine concentration modulates both its rate of synthesis and the inhibitory effects of two stimuli of O2- production.
Animals↗
Interferon-induced differentiation of U937 cells. Comparison with other agents that promote differentiation of human myeloid or monocytelike cell lines.
Effects of human fibroblast (beta) or leukocyte (alpha) interferon (IFN) on differentiations of a human histiocytic lymphoma-derived cell line (U937) or promyelocytic leukemia-derived cell line (HL-60) were studied. When cultured with beta-IFN (400-1,000 U/ml), U937 cells showed gross morphologic and microscopic changes consisting of clumping, increased cytoplasmic-to-nuclear ratio, enhanced prominence of cytoplasmic granules, and membrane ruffling. After culture with beta-IFN, the number of U937 cells reactive with B43.4.1 monoclonal antibody, which is specific for human monocytes, natural killer cells, and neutrophils, increased from less than 10% of U937 cells to 47% beta-IFN treatment also enhanced antibody-dependent cellular cytotoxicity against chicken erythrocytes by U937 cells. The same morphologic, phenotypic, and functional changes were also observed when U937 were treated with recombinant or natural alpha-IFN. The effects of alpha-IFN were totally abolished by anti-alpha-IFN serum. In contrast, HL-60, which differentiates toward cells of the monocyte lineage in response to phorbol 12-myristate 13-acetate (based on the above criteria), and toward granulocytes in response to dimethyl sulfoxide, did not differentiate when cultured with alpha- or beta-IFN. No consistent relationship between induction of differentiation and changes in phospholipid methylation were observed.
Antigens↗
Effect of interferon on phospholipid methylation by peripheral blood mononuclear cells.
The effect of human interferon (IFN) preparations on the metabolic pathway leading to the synthesis of phosphatidylcholine (PC) by a stepwise addition of methyl groups to phosphatidylethanolamine (PE) was investigated in human peripheral blood mononuclear (PBMN) cells. An inhibition of the synthesis of PC via this pathway was regularly observed with both alpha- (recombinant or natural) and beta-IFN. This inhibition was apparent within the first 5 min of treatment, reached its maximum between 15 min and 1 hr, and persisted at the same level until 6 hr, the last time point examined. Each of the transmethylated products of PE underwent a similar inhibition, as measured by the turnover rate of individual products. The intracellular pool of the methyl donors, methionine and S-adenosyl-methionine (SAM), was shown to be unaffected. The methyltransferase activity of IFN-pretreated cell extracts was unchanged. These findings support the hypothesis that IFN induces a functional change in phospholipid methylation at the level of organized membrane-bound phospholipid methyltransferase enzymes in intact cells.
Cell Membrane↗
Phospholipid methylation and phospholipase A2 activation in cytotoxicity by human natural killer cells.
The role of phospholipid methylation and phospholipase A2 (phosphatide 2-acylhydrolase, EC 3.1.1.4) in natural killer (NK) function by human peripheral blood mononuclear cells was studied. Pretreatment of effector cells with a methyltransferase inhibitor, 3-deazaadenosine, in the presence of homocysteine thiolactone, reduced cytotoxicity in a dose-dependent fashion. This effect was closely associated with inhibition of methylation of lipids but not of nucleic acids or proteins. The suggestion for a role of phospholipid methylation was supported by the observation that the interaction between NK-susceptible tumor targets and peripheral blood mononuclear cells caused increased phospholipid methylation only when susceptible target cells were used. Phospholipase A2 was also implicated in human NK activity. Inhibitors of the enzyme such as tetracaine, mepacrine, Rosenthal's inhibitor, and corticosteroids impaired NK function. Rosenthal's inhibitor was also shown to exert an inhibitory effect on a purified NK-cell population obtained by the isolation of large granular lymphocytes on Percoll gradients. Peripheral blood mononuclear cells were also directly shown to display phospholipase A2-like activity, as measured by the decrease in radioactive arachidonate from prelabeled phospholipids, specifically phosphatidylcholine, in effector cells. These data suggest that enhanced phospholipid methylation occurs during the recognition function of NK cells. Consequent activation of phospholipase A2 might be involved in the mechanisms leading to lytic events within the target cell.
Adrenal Cortex Hormones↗
Hepatitis B infection in alcoholic liver disease and primary hepatocellular carcinoma in France.
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Adult↗
[Hepatitis due to procetofene? 1 case].
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Aged↗
[Value of a therapeutic test in Whipple's disease. Apropos of 1 case].
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Erythromycin↗