[Metastasis to the breast from non mammary metastasis. Clinical, radiological characteristics and diagnostic process. A report of two cases and a review of literature]. / Métastases au niveau des seins de tumeurs extramammaires. Caractéristiques cliniques, radiologiques et démarche diagnostique. A propos de deux cas et revue de la littérature.

The metastatic involvement of the breast from non-mammary neoplasms is a relatively rare condition: 0.5 to 6% of the breast cancers. All cancers can give breast metastases, several months after the discovery of the primitive tumor or in 25% of the cases in being the first sign. Their clinical and radiological presentation polymorphic installation a problem of differential diagnosis between benign tumor, like the fibroadenomas on the one hand, and malignant tumors of other share. The presence of multiple, bilateral round tumors, superficial without the traditional signs of malignity which one meets with the primitive tumors: irregular margins, spiculations, microcalcifications, posterior cone of shadow is evocative diagnosis. The IRM finds the criteria of malignity specific to the primitive tumor. Pathologic examination completed with immunohistochemical tests is a key point for diagnosis. The search for a primitive tumor is essential, in particular for neuroendocrine carcinoma, stromal sarcoma, and the angiosarcoma which can be primitive tumors of the breast. Treatment is therefore modified, taking into consideration the treatment and prognosis of the primary disease.

[Lynch syndrome and gynaecologic's cancer: follow-up recommendations]. / Syndrome de Lynch et cancers gynécologiques: recommandations pour la surveillance.

The Lynch syndrome or HNPCC, is due to a mutation of the genes pertaining to the system MMR. This frequency varies from 1/1000 to 1/400. It's responsible for 6% of endométrial cancers, 2% of ovarian cancers and 1 to 3% of colorectal cancers. A good knowledge of this syndrome is necessary for doing the diagnosis and adjustment of gynaecological and colorectal follow-up. The authors report four cases in Lynch syndrome family.

[Botulism and pregnancy]. / Botulisme et grossesse.

Botulism during pregnancy is uncommon and raises concern due uncertainty about fetal impairment. This type of situation has not been reported to date. Treatment is basically symptomatic and based on nursing care. The prognosis is tightly correlated with the maternal status. Dietary hygiene is the basis of prevention. We describe a case of botulism occurring during the second quarter of pregnancy.

[Cost effectiveness of Ligasure Precise versus surgical clips during axillary nodal dissection for breast cancer]. / Coût efficacité du Ligasure Precise versus clips chirurgicaux lors du curage axillaire pour cancer du sein.

UNLABELLED: Introduction. The techniques used for axillary node dissection are constantly evolving. The advent of the grip Ligasure Precise raise the question of its cost-effectiveness compared with surgical clips. OBJECTIVE: To compare the effectiveness of Ligasure compared with surgical clips for simple axillary node dissection or Patey procedure in terms of duration of drainage, cost of hospitalization and complications. MATERIAL: and method. Retrospective study extending from January 1, 2003 to December 31, 2004, concerning 187 patients who underwent simple axillary dissection (100) or Patey procedure (87), with use of surgical clips or Ligasure followed by drainage. RESULTS: The use of Ligasure increased the operative cost because its price is higher than that of a clip grip with a refill. Ligasure significantly decreased the duration of drainage in the two groups but there was significantly more abundant fluid loss in the dissection group. The cost of hospitalization related to the choice of the technique of hemostasis (cost of the material + lasted of drainage X price of the day of hospitalization), was not significantly favor of Ligasure. Taking into account the choice of the hemostasis technique and the total duration of hospitalization (material cost + duration of hospitalization X price of the day of hospitalization), there is no significant difference between the two groups. CONCLUSION: This study compares grip Ligasure Precise with surgical clips for axillary dissection. The duration of drainage was significantly shorter with Ligasure Precise but its benefit in terms of fluid loss remains to be shown. The use of Ligasure does not significantly reduce the cost of hospitalization.

[Pelvic Burkitt lymphoma mimicking an ovarian tumor]. / Lymphome de Burkitt pelvien simulant un cancer de l'ovaire.

Primary malignant lymphoma of the ovary is a rare tumor (1,5% of ovarian tumors). Clinically, it occurs as an abdominal mass with pain which can be confused with an epithelial ovary tumor. Most tumors are observed during the fourth decade. Burkitt lymphoma, is sporadic in western countries, usually with abdominal involvement. Diagnosis is guided by biological analysis and imaging. Prognosis depends on medullary and neuromeningeal involvement. Polychemotherapy is required. We report a case of a young woman who developed abdominal Burkitt Lymphoma mimicking advanced-stage bilateral ovarian cancer.

IGF-II is more active than IGF-I in stimulating L6A1 myogenesis: greater mitogenic actions of IGF-I delay differentiation.

Mitogens are generally thought to inhibit myogenesis, and many cell biologists have found it hard to interpret observations that the insulin-like growth factors (IGFs) stimulate both proliferation and differentiation of muscle cells in culture. Our previous studies suggested that the Type I IGF receptor mediates these actions. However, IGF-II and insulin treatment caused myoblasts to differentiate much more extensively, suggesting that more complex mechanisms may be involved. Here we present evidence that the greater mitogenic activity of IGF-I (compared to IGF-II and insulin) delays L6A1 myoblast differentiation. Under conditions in which the mitogenic actions of IGF-I are suppressed, the stimulation of myogenesis by IGF-I approached that by IGF-II: (1) in L6A1 cultures plated at a higher cell density; (2) in L6A1 cultures in which cell proliferation was inhibited by cytosine arabinoside or aphidicolin; and (3) in cultures of primary human muscle cells, which exhibit a smaller mitogenic response to IGF-I. Further evidence that the Type I receptor plays a major role in relaying the signal for differentiation was obtained by using IGF-I and IGF-II analogs. Analogs which have reduced affinity for the Type I receptor showed a dramatic decrease in activity, while an analog with increased affinity for the Type II receptor was no more active than native IGF-I. Our results indicate that both mitogenic and myogenic actions of IGF-I are mediated by the Type I receptor. We conclude that IGF-I delays the onset of myogenesis as a result of its mitogenic actions, and only subsequently stimulates myogenesis. These observations reconcile the apparent conflict between our results with the IGFs and other investigators' reports of effects of other mitogens.

Negative feedback regulation of insulin-like growth factor-II gene expression in differentiating myoblasts in vitro.

We have previously reported that autocrine secretion of insulin-like growth factor-II (IGF-II) plays a critical role in stimulating spontaneous myogenic differentiation in vitro. Myogenesis and IGF-II gene expression are both negatively controlled by high serum growth medium, and it is likely that serum inhibits terminal differentiation at least in part by blocking autocrine secretion of IGF-II. To investigate this possibility, we assessed the effects of various serum fractions and growth factors on endogenous IGF-II gene expression in rat L6A1 myoblasts. Unexpectedly, we found that IGF-I, IGF-II, and high concentrations of insulin were potent inhibitors of IGF-II gene expression. This is the first example we have seen in which IGFs regulate their own expression by a negative feedback mechanism. Feedback inhibition was not dependent on the stimulation of cell proliferation by IGFs, and differentiated L6A1 myotubes remained sensitive to this action of the IGFs. Results with IGF analogs suggested that the inhibition of IGF-II gene expression by IGFs was mediated by the type I IGF receptor and was strongly suppressed by L6A1-secreted IGF-binding proteins. Human primary myoblasts also exhibited feedback inhibition by the IGFs, whereas the rapidly fusing mouse Sol 8 cell line did not. We conclude that IGF-II gene expression in differentiating L6A1 myoblasts is regulated by a negative feedback mechanism (unusual for the IGFs) that acts primarily through the type I IGF receptor and appears to be inhibited by IGF-binding proteins secreted by L6A1 myoblasts in low serum differentiation medium.

IGFs and muscle differentiation.

The Role of IGFs in Myogenesis. Thus we are now convinced that the control of myogenesis by IGFs is a general phenomenon that occurs in all skeletal muscle cells, whether or not IGFs are added to the "differentiation" medium. We believe that several medium components contribute to the suppression of IGF-II expression in myoblasts incubated in high serum "growth" medium, and conclude that the IGF-I receptor mediates the feedback inhibition of IGF-II gene expression in muscle cells. Mechanism of Induction of Myogenesis by IGFs. The observations summarized here now permit a reasonably coherent overview of the stimulation of myogenic differentiation by the IGFs. It seems clear that all IGFs act by binding to the Type I IGF receptor, and that this process is inhibited to a significant extent by IGF binding proteins secreted by the target myoblasts. A major, but possibly not the only relevant effect of this binding is the induction of expression of the myogenin gene; this induction appears to require the presence of myf-5 protein, at least during the early part of the response. Cells capable of a mitogenic response undergo a round of division in response to IGF-I, thus delaying their entry into the final processes of postmitotic terminal differentiation. Other laboratories have shown that myogenin complexes with one or more widely occurring proteins such as E12 or E47 to form an active complex that interacts with CAnnTG elements in muscle specific genes, turning on expression of those genes and thus initiating the phenotype associated with terminally differentiated skeletal muscle.

"Spontaneous" differentiation of skeletal myoblasts is dependent upon autocrine secretion of insulin-like growth factor-II.

Differentiation of muscle cells to form postmitotic myotubes is usually viewed as being negatively controlled by medium components, sometimes designated "mitogens." However, we have found that a family of mitogenic agents, the insulin-like growth factors (IGFs), are potent stimulators of differentiation in myoblasts which act by inducing expression of the myogenin gene. We show here that this action of the IGFs occurs even when these growth factors are not added to the cell medium; upon transfer to low-serum "differentiation medium," myoblasts begin active expression of the IGF-II gene, at both the mRNA and protein levels. Furthermore, autocrine secretion of IGF-II is essential for the process of terminal differentiation of the cells. These conclusions are based upon four lines of evidence. (1) The rate of spontaneous differentiation in several sublines of myogenic cells correlates with their level of expression of IGF-II. (2) C2 and Sol 8 cells, which secrete high levels of IGF-II, are relatively insensitive to exogenous IGFs, in contrast to L6 lines, which exhibit lower levels of IGF-II gene expression. (3) An antisense oligodeoxyribonucleotide complementary to the first five codons of IGF-II inhibits myogenic differentiation in the absence but not in the presence of exogenous IGF-II. (4) Spontaneous differentiation in response to autocrine IGF-II involves the same mechanism that occurs in cells stimulated by the IGFs, i.e. elevation of expression of the myogenin gene.

Hormones, growth factors, and myogenic differentiation.

Three families of growth factors/hormones have major effects on the differentiation of skeletal muscle cells. Two (FGF and TGF-beta) are potent inhibitors, and the third (IGF) exhibits a biphasic stimulatory action (but is not inhibitory even at high concentrations). All of these affect the expression of myogenin, one of the recently discovered family of myogenesis controlling genes, and FGF and TGF-beta have been shown to inhibit the expression of MyoD1 (and probably myf-5 and herculin) as well. These agents inhibit or stimulate (respectively) all measured aspects of myogenic differentiation--fusion, expression of a set of muscle-specific genes, and attainment of a postmitotic state--in all cells that are capable of these responses, whether cell lines or primary muscle cell cultures. It now seems clear that the myogenesis controlling genes regulate the entire family of muscle-specific proteins. Therefore the demonstration that expression of these genes is controlled (both positively and negatively) by specific growth factors that are now available at high purity and in useful quantities offers the possibility of understanding myogenic differentiation at a level of molecular detail that is very exciting.

The role of the IGFs in myogenic differentiation.

Of the three families of growth factors/hormones (the FGFs, TGF-betas, and IGFs) that have major effects on the differentiation of skeletal muscle cells, only the IGFs stimulate the process; indeed, the IGFs are the only well-defined agents thus far shown to stimulate myogenesis. All of these agents affect the expression of myogenin, one of the recently discovered family of myogenesis controlling genes, and TGF-beta and FGF inhibit the expression of MyoD1 as well. (L6 cells do not express MyoD1, so we have not looked for an effect of IGFs on it.) At least partly as a result of this action, these agents inhibit or stimulate all aspects of myogenic differentiation--fusion, expression of a set of muscle-specific proteins, and attainment of a postmitotic state--in all tested cell lines and primary muscle cell cultures. It is becoming clear that the myogenic controlling genes are capable of regulating expression of genes for the entire family of muscle specific proteins, so the principal question remaining about actions of these growth factors is the mechanism by which they inhibit or induce expression of the myogenin or MyoD1 genes. In spite of the uncertainty about their interactions, the discovery of the myogenesis controlling genes now provides a much sharper focus for studies on the processes involved in terminal differentiation of skeletal muscle cells. The demonstration that expression of these genes is controlled, both positively and negatively, by specific growth factors that are now readily available opens exciting new possibilities in endocrinology and developmental biology.

The inhibition of insulin action and glucose metabolism by porcine growth hormone in porcine adipocytes is not the result of any decrease in insulin binding or insulin receptor kinase activity.

The present study was undertaken to determine the effects of porcine growth hormone (pGH) on glucose transport, to establish which lipogenic enzymes were affected by pGH, and to determine if changes in insulin binding or insulin receptor kinase activity contributed to the diminished insulin responsiveness of adipocytes from pigs treated with pGH. Pigs were treated with pGH daily (70 micrograms/kg body wt.) for 7 days. pGH treatment reduced the basal (non-insulin-stimulated) glucose transport rate by 62% and the insulin-stimulated transport rate by 47%. The decline in glucose transport rate was paralleled by a 64% decrease in fatty acid synthesis. The reduction in the lipogenic rate was associated with a marked decline in the activity of several lipogenic enzymes: glucose-6-phosphate dehydrogenase (50% decrease), 6-phosphogluconate dehydrogenase (11% decrease), malic enzyme (62% decrease) and fatty acid synthase (activity not detectable after pGH treatment). The pGH-dependent decline in insulin responsiveness was not associated with any change in the binding of insulin to intact adipocytes or to plasma membrane preparations. The insulin-stimulated tyrosine kinase activity of the wheat-germ agglutinin-purified receptors from pGH-treated adipocytes was not different from that in control adipocytes, except when high concentrations of insulin were employed. These findings establish that pGH elicits a number of metabolic effects in porcine adipocytes which collectively diminish the rate of lipid synthesis, and thereby contribute to the decrease in lipid deposition observed in pGH-treated pigs. Furthermore, the pGH-dependent impairment in insulin action appears to be mediated at some location distal to the receptor kinase step or in other signal pathway(s) which mediate the biological effects of insulin that are not dependent on activation of insulin receptor tyrosine kinase activity.

Effects of growth factors on myogenic differentiation.

It has now been well established that the terminal differentiation of muscle cells in culture is subject to control by hormones and growth factors in the incubation medium. Thus far the most potent and most extensively studied agents are fibroblast growth factor (FGF), the insulinlike growth factors (IGFs), and transforming growth factor-beta (TGF-beta). Independent reports from several laboratories have established that both FGF and TGF-beta are potent inhibitors of differentiation and both appear to act at early stages of commitment to differentiation. Stimulation of differentiation by the IGFs (and by insulin at concentrations in the microgram/ml range) has also been observed and confirmed repeatedly. FGF and IGF are mitogenic for muscle cells, and TGF-beta either has no effect or suppresses cell proliferation, so previous generalizations that mitogens inhibit myogenic differentiation are clearly not valid when results with purified agents in well-defined media are considered. Work with oncogenes and specific toxins is beginning to reveal the mechanisms by which these agents might affect differentiation, and there is reason for optimism that an understanding of the molecular events that control terminal differentiation may be attained in the near future.