Microdissection and breast cancer.
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Breast Neoplasms↗
Biomedical subjects
A Janin
Publications and source records attributed to A Janin.
[Gorlin-Goltz syndrome. Apropos of a maxillary cyst].
We report a case of Gorlin-Goltz syndrome and recall the principle features of this uncommon disease. The syndrome associates multiple skeletal malformations, skin tumors and epidermoid maxillary cyst. We discuss the differential diagnosis of maxillary cysts.
Adult↗
[Resins polymerizing at low temperatures. I. Different families and principle technics].
For pathologists, tissue processing and analysis require good preservation of both the shape (morphology) and the content of the cells (antigens, nucleic acids). Low temperature embedding resins are the only inclusion substrate which allows both a fine morphological analysis and good preservation of antigens and nucleic acids. Automatic the technical processes and simplified protocols now allow the introduction of low temperature embedding resins in diagnostic procedures.
Cold Temperature↗
[Cryopreserved tumor cell and tissue bank. An essential role for pathologists in cancer research (Recommendations ANAES)].
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Cryopreservation↗
Stress-induced aberrant splicing of TSG101: association to high tumor grade and p53 status in breast cancers.
The TSG101 gene, identified through insertional mutagenesis, is localized in a region that exhibits LOH in human cancers, suggesting that TSG101 might be a tumor suppressor gene. Numerous studies have then shown the presence of abnormal transcripts in various tumors which appear to result from aberrant splicing of the gene, rather than from intragenic deletions. Moreover, many studies demonstrated that these aberrantly spliced transcripts were not found in matched normal tissues. We have analysed TSG101 transcripts in 85 breast cancer samples and found that abnormal splicing of the gene is tightly correlated with tumor grade and p53 mutation. In addition, stress induced the appearance of these abnormal transcripts in primary lymphocytes. Hence, TSG101 splicing defects, while unrelated to the oncogenic process per se, could reflect the cellular environment of the tumor cells. The proposed role of stress and hypoxia to select p53 mutant cells could account for the tight association with p53 status.
Alternative Splicing↗
Preoperative imaging of parathyroid glands with technetium-99m-labelled sestamibi and iodine-123 subtraction scanning in secondary hyperparathyroidism.
BACKGROUND: Parathyroidectomy is unsuccessful in 10-30% of uraemic patients operated on for secondary hyperparathyroidism. We investigated the usefulness of preoperative radionuclide imaging, with simultaneous recording of the distribution images of iodine-123 and technetium-99m-labelled sestamibi. METHODS: 11 patients with secondary hyperparathyroidism underwent prospective imaging and parathyroidectomy. Plasma concentrations of intact parathyroid hormone (PTH) were measured in all patients before and 6 months after subtotal parathyroidectomy. FINDINGS: Preoperative scanning showed 42 hot-spots suggesting enlarged parathyroid glands. 45 glands were discovered at surgery, and the parathyroidectomy was deemed successful in ten patients. Among the latter, one patient had a supernumerary parathyroid gland detected by scanning and resected from the left thymus. Another patient showed ectopic uptake corresponding to a large parathyroid gland in the upper mediastinum, and another had a parathyroid gland well above the thyroid. No false-positive scan findings were documented. In the patient for whom parathyroidectomy failed, preoperative scanning suggested five enlarged parathyroid glands, though the surgeon found only four glands, in their normal positions. Hyperparathyroidism persisted (intact PTH 527 ng/L, 6 months after surgery). A second scan confirmed the preoperative scan, showing a fifth parathyroid gland in the middle of the right thyroid lobe. INTERPRETATION: Simultaneous recording of 99mTc-sestamibi and 123I improved the imaging of parathyroid glands in secondary hyperparathyroidism. The technique can identify ectopic and supernumerary parathyroid glands.
Adult↗
Retinoic acid and arsenic synergize to eradicate leukemic cells in a mouse model of acute promyelocytic leukemia.
In acute promyelocytic leukemia (APL) patients, retinoic acid (RA) triggers differentiation while arsenic trioxide (arsenic) induces both a partial differentiation and apoptosis. Although their mechanisms of action are believed to be distinct, these two drugs both induce the catabolism of the oncogenic promyelocytic leukemia (PML)/RARalpha fusion protein. While APL cell lines resistant to one agent are sensitive to the other, the benefit of combining RA and arsenic in cell culture is controversial, and thus far, no data are available in patients. Using syngenic grafts of leukemic blasts from PML/RARalpha transgenic mice as a model for APL, we demonstrate that arsenic induces apoptosis and modest differentiation, and prolongs mouse survival. Furthermore, combining arsenic with RA accelerates tumor regression through enhanced differentiation and apoptosis. Although RA or arsenic alone only prolongs survival two- to threefold, associating the two drugs leads to tumor clearance after a 9-mo relapse-free period. These studies establishing RA/arsenic synergy in vivo prompt the use of combined arsenic/RA treatments in APL patients and exemplify how mouse models of human leukemia can be used to design or optimize therapies.
Animals↗
Eosinophilic airway inflammation in nasal polyposis.
BACKGROUND: Asthma and asymptomatic bronchial hyperresponsiveness (BHR) are frequent findings in patients with nasal polyposis (NP). OBJECTIVE: To elucidate mechanisms responsible for the development of BHR, we initiated a prospective study of bronchial inflammation as assessed by bronchial lavage (BL) and bronchial biopsy specimens in 35 patients with noninfectious NP. METHODS: BHR was determined with methacholine provocation testing. Differential cell count, ECP, and histamine and tryptase levels were determined in BLs. Pathologic examination of bronchial biopsy specimens was performed with May-Grünwald-Giemsa stain to assess the number of lymphocytes. Indirect immunoenzymatic methods were used to identify eosinophils and mast cells. RESULTS: Fourteen patients did not exhibit BHR (group A); 7 patients had asymptomatic BHR (group B); and 14 patients had BHR associated with asthma (group C). Patients of group C tended to have a longer duration of nasal symptoms than those of groups A and B. FEV1 (L) was significantly lower in group C than in groups A and B. The number and percentage of eosinophils were significantly higher in BLs in groups B and C than in group A (P <. 05). Patients of groups B and C had a significantly higher number of eosinophils in bronchial submucosa (14.0 +/- 1.5/mm2 and 19.0 +/- 1. 9/mm2, respectively) than patients of group A (0.1 +/- 0.1/mm2). The number of lymphocytes was also higher in groups B and C than in group A. FEV1 (percent of predicted value) and eosinophil number within bronchial mucosa correlated negatively. CONCLUSION: Our results demonstrate that patients with NP and asymptomatic BHR had an eosinophilic bronchial inflammation similar to that observed in asthmatic patients with NP, whereas patients with NP without BHR do not feature eosinophilic lower airways inflammation. The clinical relevance of these results requires careful follow-up to determine whether eosinophilic inflammation in these patients precedes and is responsible for the development of obvious asthma.
Adult↗
Interleukin-5 immunoreactivity and mRNA expression in gut mucosa from patients with food allergy.
BACKGROUND AND AIMS: Eosinophils, mast cells and T lymphocytes are important cells in the allergic inflammatory process. These cells produce and are regulated by cytokines such as interleukin-3 (IL-3), interleukin-5 (IL-5) and granulocyte macrophage-colony stimulating factor (GM-CSF). We initiated this study to evaluate pathological abnormalities and to detect IL-5 in the duodenal mucosa from patients with food allergy. METHODS: Endoscopy duodenal biopsy specimens were obtained from seven food-allergic patients, six atopic healthy controls and six nonatopic healthy controls. IL-5 protein was evaluated by immunohistochemistry. Electron microscopy as well as double immunofluorescent staining were used to identify the labelled cells and to localize IL-5. IL-5 mRNA expression was evaluated by qualitative polymerase chain reaction. RESULTS: A significantly increased number of lymphocytes, mast cells and eosinophils was detected in the lamina propria in food-allergic patients and, in lower number, in atopic controls. Immunostaining for IL-5 was markedly positive in food-allergic patients, slightly increased in atopic controls and negative in nonatopic controls. Ultrastructurally, in food-allergic patients and in atopic controls, IL-5 was localized in eosinophil granules, in the matrix of intact granules and at the periphery of altered granules. Double immunofluorescent staining was performed in food-allergic patients and showed that 86.7% of IL-5+ cells were eosinophils, and that IL-5 was expressed by 24% of eosinophils. IL-5 mRNA was expressed in food-allergic patients but was not detected in atopic and nonatopic controls. CONCLUSION: Activated eosinophils are involved in gut atopic reactions occurring in food allergy and are probably in part upregulated by their own local production of IL-5.
Adolescent↗
Acute inflammatory intestinal vascular lesions and in situ abnormalities of the plasminogen activation system in Crohn's disease.
OBJECTIVES: The distribution of the intestinal vascular lesions and their relation with the fibrinolysis process are poorly known in Crohn's disease (CD). The mediators of the plasminogen activator system, namely urokinase-type plasminogen activator (u-PA), tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type-1 (PAI-1), are a key complex involved in fibrinolysis. The aims of this study were: (1) to further define vascular lesions and their distribution in the intestine; and (2) to study concomitantly the qualitative in situ expression and the levels of u-PA, t-PA and PAI-1 in the ileum of patients with CD. PATIENTS AND METHODS: Histological, immunohistochemical and ultrastructural studies of vascular lesions in the resected ileum of 27 patients with CD were performed and compared with 36 control patients. Levels of u-PA, t-PA and PAI-1 measured by ELISA methods were compared in healthy and inflamed ileal tissues of 17 patients with CD. RESULTS: Acute vascular lesions involving mainly serosal venules and capillaries were present in 63% of patients with CD vs 3/36 controls and were associated with PAI-1 expression. They were prominent on the mesenteric border beneath macroscopically normal mucosa. In contrast, chronic vascular lesions were present in all layers beneath mucosal ulcerations, where a significant increase of PAI-1 levels was found. CONCLUSIONS: These results suggest that vascular involvement associated with abnormalities of PAI-1 expression is an early and widespread event in CD. Their prominence on the mesenteric border might explain the characteristic location of CD ulceration along the mesenteric margin.
Adolescent↗
[Eruptive epithelioid hemangioendothelioma with spindle cells. Nosological place in the spectrum of epithelioid vascular tumors].
The epithelioid vascular tumors include epithelioid hemangioma, epithelioid hemangioendothelioma and epithelioid angiosarcoma. We report the case of a difficult to define vascular epithelioid tumor. The tumor localized in the head developed in an eruptive way in multiple bone and skin locations in a 22-year-old man. The lesions had the same histological features as those of epithelioid hemangioma and epithelioid hemangioendothelioma with a spindle-cell component. This tumor was called eruptive epithelioid hemangioendothelioma with spindle cells. In our case, its development with recurrences and destructive features has some similarities to tumors of intermediate malignancy.
Adult↗
[Tissue microdissection: application to the study of cancer of the breast].
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Breast Neoplasms↗
[An unusual diverticular sigmoid disease].
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Aged↗
Squamous cell carcinomas after allogeneic bone marrow transplantation for aplastic anemia: further evidence of a multistep process.
BACKGROUND: Secondary solid tumors are rare events occurring in patients who underwent allogeneic marrow transplantation for aplastic anemia and Fanconi's anemia. Human herpes virus 8 (HHV8), Epstein-Barr virus (EBV), and human papillomaviruses (HPV) sequences have been found in squamous cell carcinoma (SCC) occurring in organ transplant recipients. The tumor suppressor gene p53 has been strongly linked to the occurrence of SCC in the nonimmunocompromised population. PATIENTS AND METHODS: In eight patients with SCC, we searched for HHV8, EBV, varicella zoster virus, adenovirus, and HPV sequences from DNA extracted from selected areas of SCC. We also looked for p53 expression in those specimens as well as the presence of anti-p53 antibodies in the serum of these patients at the onset of SCC. RESULTS: In one patient, we found the presence of both HHV8 and EBV sequences, and in another patient we found HPV16 sequences. All five tumors that could be studied disclosed evidence of p53 accumulation, but none of the eight patients had anti-p53 antibodies in the sera. CONCLUSION: SCC developing in marrow transplant recipients seems to occur via a multistep process. Genetic predisposition may be present, as in patients with Fanconi's anemia. Transplantation-related factors, such as irradiation and chronic graft-versus-host disease, also have a role. In this article, we add two more potent risk factors: p53 alteration(s) and in some cases the presence of oncogenic viruses.
Anemia, Aplastic↗
Transgenic mice for MTCP1 develop T-cell prolymphocytic leukemia.
T-cell prolymphocytic leukemia (T-PLL) is a rare form of mature T-cell leukemia associated with chromosomal rearrangements implicating MTCP1 or TCL1 genes. These genes encode two homologous proteins, p13(MTCP1) and p14(TCL1), which share no similarity with other known protein. To determine the oncogenic role of MTCP1, mice transgenic for MTCP1 under the control of CD2 regulatory regions (CD2-p13 mice) were generated. No abnormality was detected during the first year after birth. A late effect of the transgene was searched for in a cohort of 48 CD2-p13 mice aged 15 to 20 months, issued from 3 independent founders. Lymphoid hemopathies, occurring in the three transgenic lines, were characterized by lymphoid cells with an irregular nucleus, a unique and prominent nucleolus, condensed chromatin, a basophilic cytoplasm devoid of granules, and an immunophenotype of mature T cells. The molecular characterization of Tcrb rearrangements demonstrated the monoclonal origin of these populations. Histopathological analysis of the cohort demonstrated early splenic and hepatic infiltrations, whereas lymphocytosis and medullar infiltrations were found infrequently. The engraftment of these proliferations in H2-matched animals demonstrated their malignant nature. Cumulative incidence of the disease at 20 months was 100%, 50%, and 21% in F3, F4, and F7 lines, respectively, and null in the control group. The level of expression of the transgene, as estimated by Western blotting in the transgenic lines correlated with the tumoral incidence, with the highest expression of p13(MTCP1) being found in F3 mice. CD2-p13 transgenic mice developed an hemopathy similar to human T-PLL. These data demonstrate that p13(MTCP1) is an oncoprotein and that CD2-p13 transgenic mice represent the first animal model for mature T-PLL.
Animals↗
Hodgkin's disease of donor origin after allogeneic bone marrow transplantation for myelogeneous chronic leukemia.
Secondary malignancies (lymphomas, leukemias, and solid tumors) occurring after bone marrow transplantation are now more frequently reported, as the patients surviving the early phase of the graft and remaining free of their original disease are more numerous. Besides early Epstein-Barr virus-associated B-cell lymphoproliferative diseases, which are the most common type and most often of donor origin, few late-occurring lymphomas have been described that might represent a distinct entity. We report here a case of Hodgkin's disease developing 8 years after allogeneic bone marrow transplantation for chronic myelogeneous leukemia. Only two Hodgkin's diseases after allogeneic bone marrow transplantation have been reported in the literature so far. The case we report is of interest because of its donor origin and its association with Epstein-Barr virus infection.
Adult↗
Similar IL-5, IL-3, and GM-CSF syntheses by eosinophils in the jejunal mucosa of patients with celiac disease and dermatitis herpetiformis.
Celiac disease (CD) and dermatitis herpetiformis (DH) are gluten-sensitive diseases with different clinical features that can initiate similar intestinal changes. The flat-destructive stage corresponds to severe lesions involving activated T-cells. However, other inflammatory cells such as eosinophils are also abundant. The mechanisms for the intestinal recruitment of eosinophils in patients with CD and DH remain unknown. Eosinophil recruitment and activation are induced in vitro by three main cytokines: interleukin-3 (IL-3), interleukin-5 (IL-5), and granulocyte-macrophage colony-stimulating factor (GM-CSF). In this study, IL-3, IL-5, and GM-CSF were detected by immunohistochemistry in all patients with CD and DH but not in the control group. By ultrastructural immunogold staining, these three cytokines had the same subcellular localization in the granule matrix of eosinophils. This result suggests that eosinophils may be involved in the immune response at the flat-destructive stage of both CD and DH.
Adolescent↗
Adverse events in phase-I studies: a report in 1015 healthy volunteers.
OBJECTIVE: This report describes all clinical, laboratory and electrocardiographical adverse events detected in healthy volunteers in a phase-I centre over a 10-year period: 54 phase-I studies are involved, including 1015 healthy young volunteers (993 males) who received 1538 treatments (23 different active drugs or placebo) corresponding to 12143 days of follow-up. This updates a similar report published previously in the European Journal of Clinical Pharmacology. METHODS: Adverse events were defined as all events noted in case-report forms. Incidence of adverse events was defined as the ratio between the number of adverse events and the number of follow-up days. Severity was rated as death, life-threatening, severe or minor. Incidences or occurrence rates were compared using the Chi-squared test with Yates' correction. RESULTS: The overall incidence of adverse events was 12.8% with a significant difference between active-drug (13.7%) and placebo (7.9%) treatments. There were 1558 adverse events of 110 distinct kinds. Only for three (headache, diarrhoea and dyspepsia) was the incidence superior to 10 per thousand. Most of these adverse events were also observed with placebo. Ninety-seven percentage of adverse events were of minor intensity; forty three (3%) were rated as severe, including nine worrying cases - six malaises with loss of consciousness, one atrial fibrillation, one hyperthyroidism and one bicytopenia. Some of the adverse events were not related to the tested drugs, but to a vagal reaction or to study conditions. There was no death or life-threatening event. The global rate of occurrence was one adverse event per treatment, one and a half per subject and one out of eight follow-up days. No difference in the overall incidence with placebo was observed between the two successive 5-year periods. CONCLUSIONS: This report confirms that adverse events in phase I studies are very common, usually of minor intensity and rarely severe; even though exceptional, life-threatening adverse events are possible. Adverse events occurring in phase I are rarely published, leading to lack of information. Thus, authors invite clinical research organization (CROs) and phase-I centres to regularly publicise at least severe adverse events; they also suggest that the life-threatening adverse events reported to health authorities should be publicised, for example by the World Health Organization (WHO).
Adult↗