[Comparative study of inflammatory and non-inflammatory locally advanced breast cancer - the experience of a Moroccan hospital]. / Étude comparative du cancer du sein localement avancé inflammatoire et non inflammatoire : expérience d'un centre hospitalier marocain.

OBJECTIVES: The locally advanced breast cancer (LABC) covers large tumor heterogeneity. It consists of non-inflammatory LABC and inflammatory breast cancer (IBC). This study aimed to compare the epidemiological, clinical and pathological, as well as the prognosis of IBC versus non-inflammatory LABC. METHODS: This is a retrospective study of 150 cases of IBC and non-inflammatory LABC collected in medical oncology department of the CHU Hassan II of Fez during a period of 4 years [January 2009-January 2013]. Overall survival (OS) and disease-free survival (DFS) were calculated using the Kaplan-Meier method. Analysis of the various prognostic factors was performed according to the Cox model. RESULTS: IBC represented 28.7% of LABC. The median age was 47 years. The median tumor size was greater in non-inflammatory LABC compared with IBC (9.5 versus 6cm; P=0.0014). Lymph node invasion was more common in the IBC (49.7% versus 45.9%; P=0.01). An SBR grade 3 was more frequently noted in the IBC (P=0.011). The two groups were well balanced with regard to HR, HER2 status and pathologic complete response. Non-inflammatory LABC had the best OS and DFS (24 vs. 22 months; P=0.03 and 18 vs. 17 months; P=0.025 respectively). CONCLUSION: IBC has a worse prognosis compared to non-inflammatory LABC. New therapeutic approaches are needed to improve the prognosis of these patients.

Autocorrelation method adapted to generate new atomic environments: application for the prediction of 13-C chemical shifts of alkanes.

The concept of the multifunctional autocorrelation method governing global description of molecules was changed in order to take into account the structural environment of each atom. New atomic environments are generated as possible descriptors in QSARs and can be useful for database characterization. The principles of this approach are widely explained through a case study dealing with the design of a model allowing the simulation of the carbon-13 nuclear magnetic spectra for alkanes. Carbon atoms in alkanes are described by using as structural descriptors a vector corresponding to only four components vectors of the multifunctional autocorrelation method. The statistical method used for deriving the model was a classical three-layer feedforward neural network trained by the back-propagation algorithm and multilinear regression (MLR). The predictive ability of the ANN model was tested by -10%-out(L10%O) cross-validation method, demonstrating the superior quality of the neural model. The established model allows us the prediction of the 13-C chemical shifts with success because since all types of carbons are taken into account without distinction of connectivity. The neural network possessed a 4:7:1 architecture with a sigmoid shape as a activation function. The model produced a cross-validation standard coefficient r between delta(exp) and delta(calc) about 0.99, while the cross-validation standard s and the mean error are equal to 0.87 and 0.60 ppm, respectively.

Trauma and extended separation from family among Latin American and African refugees in Montreal.

Although the vast majority of refugees have suffered trauma and extended separation from their families in exile, little is known about the interactions between these two types of experience. The qualitative and quantitative analyses of data gathered from 113 refugees from Latin America and Africa suggest that the joint occurrence of trauma and separation has a significant impact on emotional distress and confirm that the family plays a key role as an anchor of emotion and identity.

Early events of human T lymphocyte activation are associated with type I protein kinase A activity.

Human T lymphocytes possess both the type I and II isozymes of protein kinase A (PKA). The type I (PKA-I) isozyme is predominantly associated with the plasma membrane, whereas the type II (PKA-II) isozyme is primarily localized to the cytosol. Because the functions of both PKA-I and PKA-II isozymes in the biochemical events of T lymphocyte activation have not been clearly elucidated, we tested the hypothesis that very early events of normal human T lymphocyte activation are mediated by the PKA-I and/or PKA-II isozyme(s). Fresh normal human T cells and a normal human CD4+ T cell line (GK606) activated with anti-CD3-epsilon and recombinant interleukin 1 alpha (rIL-1 alpha) exhibited a peak six- to sevenfold increase of PKA phosphotransferase activity at 5 min that returned to baseline by 60 min. Similarly, both fresh T cells and the T cell line activated by phorbol myristate acetate and ionomycin demonstrated a peak eightfold increase of PKA activity by 15 min that returned toward baseline by 60 min. Chromatographic separation of the PKA isozymes and quantification of phosphotransferase activities after T cell activation by either agonist pair showed preferential activation of the PKA-I isozyme, resulting in a significant reduction in the ratio of PKA-I to PKA-II isozyme activity from 3.1:1-6.2:1 to 1.1:1-3.2:1. PKA-I isozyme activation resulted in the release of free catalytic (C) subunit, an increase in C subunit phosphotransferase activity, and the phosphorylation of T cell plasma membrane-associated proteins, p14, p17, p20, p21, p38, and p48. However, activation of the PKA-I isozyme did not appear to be required for the transcription of IL-2 mRNA, an event necessary for mitosis. These data indicate that ligand-induced T cell activation is associated with rapid activation of the PKA-I, but not PKA-II, isozyme that results in phosphorylation of plasma membrane-associated proteins. The involvement of the PKA-I isozyme during the very early events of T cell activation suggests that this isozyme may be an antigen- or mitogen-stimulated protein kinase.

Photosensitization of L1210 leukaemic cells by argon laser irradiation after incubation with haematoporphyrin derivative and rhodamine 123.

The selectivity and efficacy of photodynamic therapy (PDT) may be improved by the combined use of photosensitizers in a similar manner to the combined use of drugs in cancer chemotherapy. Two photosensitizers (haematoporphyrin derivative (HPD) and rhodamine 123 (Rh-123) were analysed which can be irradiated at the same wavelength (514 nm), are preferentially taken up by tumour tissue and are not specific for the same target (membrane for HPD, mitochondria for Rh-123). The analysis of the phototoxic effects in surviving fractions showed a dependence on dose for both products and a dependence on incubation time for HPD but not Rh-123. The lethal dose for 50% cell death (LD50) for HPD increased from 25 to 56 J cm-2 when the HPD dose was reduced from 2.5 to 1 micrograms ml-1 for the same incubation time. When the incubation time was increased from 15 to 45 min, the surviving fraction decreased by 37% and 17% for doses of 1 and 2.5 micrograms ml-1 respectively. For low doses (0.5 and 1 microgram ml-1), the toxicity of the two photosensitizers added simultaneously was weaker than for Rh-123 alone, whereas for high doses (2.5 micrograms ml-1) the surviving fraction was less than that obtained with Rh-123 alone. These results were compared with the light energy absorbed, the quantum yield of singlet oxygen and Rh-123 uptake as determined by flow cytometry analysis.

[Effect of gastrin and enprostil, a PGE2 analog, on colonic cancerous cell growth]. / Influence de la gastrine et de l'enprostil, analogue de la PGE2, sur la croissance de cellules cancéreuses coliques.

The effects of gastrin (G-17), proglumide (a gastrin receptor antagonist), and enprostil (a synthetic analog of prostaglandin E2) used alone or in association were studied in colonic cancer Prob and Regb cell growth. The Prob (progressive in BD IX rats) and Regb (regressive) cell lines were cloned from a single chemically-induced rat colonic cancer. After a serum-free period corresponding to one doubling cell time, cells were incubated with 100 to 1,200 pM G-17, 40 or 80 mM proglumide, and 2.5 to 5 micrograms/ml enprostil for 8 h. Cell growth was measured 48 h later by colorimetric MTT assay. Two and four hundred pM G-17 gave a growth stimulation of 17.4 percent and 31 percent for Prob cells respectively or 35.5 percent and 49 percent for Regb cells. Growth stimulation was found to be statistically different (P less than 0.01) for Prob and Regb cells. Proglumide partially inhibited this growth stimulation whereas enprostil inhibited in totally. These results suggest that growth of some colonic cancer cell lines may be G-17 dependent. However the intensity of cell-growth stimulation depends on the level of cell malignancy or differentiation in a single tumor.

Glucocorticoid effects and receptors in two rat colon carcinoma cell lines differing by their tumorigenicity.

Steroid hormones, regulators of cell differentiation and proliferation, are believed to play a role in carcinogenesis. Glucocorticoid hormones in particular modulate the expression of a number of proteins implicated in this process. We have investigated the effect of dexamethasone on two cell lines derived from a colon carcinoma, which differ by their tumorigenicity. Dexamethasone was found to inhibit growth of both the progressive (PROb) and the regressive clone (REGb). Upon hormonal treatment, glucocorticoid hormones induced fibronectin secretion by the two clones, whereas PROb cells were found to secrete an additional Mr approximately 43,000 protein. The cellular effect of glucocorticoid hormones being mediated through a specific soluble receptor, we have characterized this protein. The progressive cells (PROb) contained more specific glucocorticoid-binding sites (approximately 170,000 sites per cell) than the regressive ones (REGb cells; approximately 100,000 sites per cell). In both clones, the receptor was associated with the Mr approximately 90,000 heat shock protein to yield large complexes (Stokes radius Rs approximately 7.5 nm), which were dissociated to the same extent upon heat- and salt-treatment. The steroid- and DNA-binding unit of the receptor, characterized under denaturing conditions using an anti-receptor monoclonal antibody was found to be more degraded in the progressive cell line.

Fucose and galactose receptor and liver recognition by lymphoma cells.

A syngeneic model system for the study of metastases is described. The system consisted of 2 lymphoma clones (A/63-I and A/63-2) derived from a single thymoma (A/63) induced by a wild-type Abelson-Moloney viral complex. Phenotype and genotype analyses revealed that both clones were derived from transformation of early T-cell precursors. An in vivo study of the colonizing potential following intravenous (i.v.) injection of clones showed that only the A/63-I cell clone colonized the liver. This observation was confirmed by quantitative analysis of organ distribution of both cell clones consecutive to i.v. injection of 125IUdR-labelled cells. In the same way, an in vitro study of the invasive potential of both clones was performed on frozen liver sections and showed that only the A/63-I cell clone had the ability to attach to liver. This specific adhesion was inhibited by L-fucose, D-galactose, N-acetyl-D-galactosamine (D-GalNAc) and with D-galactose- and L-fucose-containing neoglycoproteins. Differences in cell surface carbohydrates of the 2 cell clones were detected using various lectins: peanut agglutinin (PNA), Dolichos biflorus (DBA), Aleuria aurantia (AAA) and Galactia tenuiflora agglutinins (GTA). A/63-I was found to react strongly with PNA, DBA and GTA, and the removal of sialic acid by neuraminidase treatment increased DBA and PNA receptor sites of A/63-2 as compared to A/63-I. The present data suggest that cell-surface GalNAc, galactosyl and fucosyl residues are responsible for the ability of the A/63-I cell clone to recognize liver tissue probably through binding to a Kupffer-cell-associated lectin.

Correlation between cell surface oligosaccharides and tissue target-selective adhesion of two rat adenocarcinoma cell lines.

We observed that two rat colon adenocarcinoma variants originating from a single parental cell line and differing by their progressive and metastatic capacities in syngeneic BDIX rats differed by their organ distribution after intravenous injections. The PROb cells accumulated in the lung, wherefrom the REGb cells were rapidly cleared. In order to explore the role of cell surface glycoconjugates in organ-specific metastasis, cytofluorometric and histochemical studies using labelled lectins were performed. This revealed that the metastatic variant PROb presented more alpha-L-Fuc(1----2) beta D-Gal-R structures than the regressive nonmetastatic variant REGb. At variance, REGb cells exposed more D-galactosyl and N-acetyl-D-galactosaminyl residues than PROb cells. Monosacharides inhibited specifically cell adhesions on frozen organ sections. L-Fuc and N-acetyl-D-galactosamine (D-GalNAc) most strongly inhibited the adhesion of PROb cells on lungs, whereas D-Gal and D-GalNAc most strongly inhibited that of REGb cells. On the liver, adhesions of both cell lines were inhibited by D-Gal and D-GalNAc. These observations support the involvement of sugar-lectin receptors in the adhesion of these cells to the lungs or liver. The possible involvement of previously described lectins is discussed.

Endothelial cell growth regulation by PGE1 analog misoprostol and indomethacin.

The role of prostaglandins on growth regulation of different cell types was investigated. We studied the effect of exogenous misoprostol in the presence or absence of indomethacin on the cell growth kinetics. Our results clearly show that misoprostol strongly inhibited the growth of several cancer cells but only slightly affected that of endothelial cells. Moreover, indomethacin alone (which decreases PG synthesis) had little effect on DNA synthesis in endothelial cells or C6 cells but inhibited colonic cancer cells. Conversely, misoprostol stimulated DNA synthesis in endothelial or C6 cells preincubated with indomethacin. This phenomenon was not observed with colonic cancer cells. The role of NSAIDs in the field of cytoprotection is discussed.

Biochemistry and metabolism of Giardia.

Giardia lamblia, an aerotolerant anaerobe, respires in the presence of oxygen by a flavin, iron-sulfur protein-mediated electron transport system. Glucose appears to be the only sugar catabolized by the Embden-Meyerhof-Parnas and hexose monophosphate pathways, and energy is produced by substrate level phosphorylation. Substrates are incompletely oxidized to CO2, ethanol and acetate by nonsedimentable enzymes. The lack of incorporation of inosine, hypoxanthine, xanthine, formate or glycine into nucleotides indicates an absence of de novo purine synthesis. Only adenine, adenosine, guanine and guanosine are salvaged, and no interconversion of these purines was detected. Salvage of these purines and their nucleosides is accomplished by adenine phosphoribosyltransferase, adenosine hydrolase, guanosine phosphoribosyltransferase and guanine hydrolase. The absence of de novo pyrimidine synthesis was confirmed by the lack of incorporation of bicarbonate, orotate and aspartate into nucleotides, and by the lack of detectable levels of the enzymes of de novo pyrimidine synthesis. Salvage appears to be accomplished by the action of uracil phosphoribosyltransferase, uridine hydrolase, uridine phosphotransferase, cytidine deaminase, cytidine hydrolase, cytosine phosphoribosyltransferase and thymidine phosphotransferase. Nucleotides of uracil may be converted to nucleotides of cytosine by cytidine triphosphate synthetase, but thymidylate synthetase and dihydrofolate reductase activities were not detected. Uptake of pyrmidine nucleosides, and perhaps pyrimidines, appears to be accomplished by carrier-mediated transport, and the common site for uptake of uridine and cytidine is distinct from the site for thymidine. Thymine does not appear to be incorporated into nucleotide pools. Giardia trophozoites appear to rely on preformed lipids rather than synthesizing them de novo.(ABSTRACT TRUNCATED AT 250 WORDS)

[Hemangio-endotheliosarcoma of the right atrium]. / Hémangio-endothéliosarcome de l'oreillette droite.

In reporting a case of haemangiosarcoma of the right atrium the authors emphasize the problems encountered in the diagnosis of primary tumours of the heart. The patient was a 50-year old woman who complained of digestive disorders and palpitations. Physical examination showed signs of right heart failure associated with a systolic murmur on the right side of the sternum. ECG gave normal results. Echocardiography displayed a pouch with liquid ultrastructure communicating with the right atrium. Angiography confirmed the presence of a cavity with irregular borders communicating with the right atrium. Coronary arteriography showed an abnormal disorderly distribution of the right coronary artery branches with newly formed vessels extending toward the tumour. At exploratory thoracotomy a large liquid tumour was found which bled at the slightest touch and was attached to the mediastinum and the right pericardium. The pleura and the lung contained several nodules of the same venous colour as the mother tumour. Extemporaneous biopsy and pathological analysis were in favour of a haemangiosarcoma. The patient died a few days after the thoracotomy.

[Circumstances in the detection of carcinoma in situ of the breast. Apropos of 12 cases]. / Les circonstances de découverte des carcinomes in situ du sein. A propos de 12 cas.

In France, 7,000 women die yearly of cancer of the breast, and 25,000 new cases are registered. The seriousness of the illness and its frequency show how important it is to diagnose it early at a stage before invasion or in situ (where 95 to 100% can be cured). In 4 years, at the University Hospital of Rennes, 90 out of 446 patients who were operated on for breast lesions had invasive cancer of the breast, i.e. 20%. 12 had a carcinoma in situ of the breast (C.I.S.E.), constituting 2.6%, of which 9 were in situ duct carcinomas and 3 in situ lobular carcinomas. In situ carcinoma of the breast can take almost any clinical form (a nodule, pain in the breast, mastitis, blood stained discharge from the nipple or Paget's disease). This means that lobular carcinoma in situ is always a surprise when diagnosed histologically in a lesion that is clinically benign. Since the anatomo-pathological diagnosis is difficult, a simple examination of the breast is not to be relied on in cases of carcinoma in situ of the breast. Mammography is the only truly valuable investigation in early diagnosis of C.I.S.E.

Premeiotic and Meiotic Instability Generates Numerous b2 Mutation Derivatives in Ascobolus.

We have studied the genetic characteristics of an unstable mutation located in the central region of the b2 gene of the fungus Ascobolus. In crosses to wild type, this spontaneous white ascospore mutation (G0 ) gives rise to a stable white spored derivative (G1) at a frequency of 5 x 10(-3). G1 is a frameshift mutation and differs from G0 by its gene conversion pattern. In self crosses, G0 gives asci with colored spore derivatives at a frequency of 1 x 10(-3). We isolated and analyzed genetically 97 independent colored derivatives ("G2" series). All but one are pseudorevertants. By the criteria of phenotype and gene conversion pattern with wild type and with G1, the pseudorevertants represent at least 13 distinct classes. Two of them are large silent deletion mutations. In crosses with wild type, some G2 derivatives, represented by G21, continue to exhibit instability, G21 yields white spored b2 mutant derivatives at a frequency of 2.6 x 10(-3). In turn, some of these "G3" mutants are themselves unstable. All the derivatives lie at the same site within the b2 locus as the parental mutation G0 . Different mutations in the G series manifest their instability at different times in the Ascobolus life cycle. Derivatives of G0 arise premeiotically (leading to two derivative meiotic products among the four), while those of G21 arise during meiosis (leading to only one derivative out of four products). The characteristics of the G instability system are similar to those of unstable mutations in other eukaryotes which are due to insertion of mobile elements.

[Lobular carcinoma in situ of the breast. Apropos of 3 cases]. / Carcinomes lobulaires in situ du sein. A propos de 3 cas.

The authors explain the particular nature of these multifocal tumors: absence of node involvement, difficulties of diagnosis, relatively favorable prognosis and a therapeutic dilemma: limited procedure with strict surveillance, subcutaneous bilateral mastectomy.

[Cancer of the ovary and pregnancy. Apropos of a case]. / Cancer de l'ovaire et grossesse. A propos d'un cas.

Following a case of ovarian cancer diagnosed during pregnancy, the authors examined the problems of screening for ovarian tumors and management of tests and treatment.

[A case of an adult triatrial heart, associated with partial abnormal venous return from the left lung]. / A propos d'un cas de coeur triatrial de l'adulte associé à un retour veineux anormal partiel du poumon gauche.

The authors underline the value of echocardiography in the diagnosis and postoperative management of a case of cor triatrium. The patient was a 22 year old male who presented with dyspnoea of effort (stage III of the NYHA classification) and clinical signs of an infundibulo-pulmonary syndrome with tricuspid regurgitation. Chest X-ray revealed cardiomegaly (CTI = 61%) and filling-in of the aorto-pulmonary window. The electrocardiogram showed left atrial and right ventricular hypertrophy. The echocardiogram, the key to diagnosis, showed an abnormal echogenic structure within the left atrium. Cardiac catheterisation demonstrated pulmonary hypertension and a difference of pressure between the two lungs. The membrane dividing the left atrium and partial anomalous pulmonary venous drainage from the left lung into the superior vena cava were visualised on late stage pulmonary angiography. Surgical excision of the membrane in the left atrium and ligation of the anomalous venous drainage provided a radical cure to all these malformations.