Epidemiology and risk factors of colorectal cancer in Syria: a single-center retrospective study.

OBJECTIVE: Colorectal cancer represents the third most common malignancy and the second leading cause of cancer deaths worldwide. Many factors contribute to the risk of developing colorectal carcinoma including diet, lifestyle, age, and genetic abnormalities.  Recent findings have shown a considerable increase in the incidence rate of CRC in developing countries. However, there is little information regarding its incidence in the Middle East countries, including Syria. With our manuscript we aimed at presenting the first large epidemiological study regarding colorectal carcinoma incidence in Syria. PATIENTS AND METHODS: We conducted a retrospective study on colorectal carcinoma cases at our institution from 2014 to 2018. The data include the cases that were diagnosed and recorded based on multiple parameters including gender, age, year of diagnosis, city of origin, and profession. RESULTS: The number of colorectal cancer cases was 1,117 out of 13,589 cases of all malignant tumors recorded from 2014 to 2018, with an annual average incidence of 8.2%. There was a statistically significant difference in CRC cases according to age and gender. We also found a statistically significant difference according to physical activity and occupation. CONCLUSIONS: These results demonstrate that risk factors related to colorectal cancer incidence in Syria mainly include male sex, age over 50 years old, and occupation with no physical activity.

Dermatophytic disease with deficit in CARD9: A new case with a brain impairment.

INTRODUCTION: Dermatophytic disease individualized by Hadida and Schousboe in 1959 is a rare form of chronic dermatophyte infection; characterized by subcutaneous and visceral invasion and a therapeutic failure. We report a case of dermatophytic disease with brain abscess in an Algerian patient. OBSERVATIONS: The patient was 47-year-old, she was born parents first cousins. She had since the age of 10 years scaly scalp lesions that became secondarily papular and nodular. At the age of 17 years, the patient had a generalized skin involvement with multiple nodular lesions, diffuse disease of the nails (plurionyxis), poly lymphadenopathies affecting the cervical, axillary and inguinal areas. Mycological tests identified Trichophyton rubrum. Histopathological examinations showed caseiform necrosis with epithelioid and giant cells. PAS staining showed hyphae in necrosis. The rest of the blood and urine tests were normal. Sequencing CARD9 allowed to highlight a homozygous mutation Q289X. The evolution was marked by an appearance at the age of 47 of a right cerebral abscess fronto-temporo-parietal, cortico-subcortical detected by MRI. The patient was given itraconazole 200mg/day with good evolution after three months of decline. DISCUSSION: Dermatophytic disease is very rare. Fifty cases have been published, mostly from North Africa, a strong endogamy region. Signs and symptoms almost always start with a scalp ringworm with almost constant occurrence of complications: in our patient a cerebral localization with a good evolution with itraconazole. Immunologically it is characterized by an autosomal recessive deficiency CARD9. This observation is notable for the onset of the disease at an early age, the dermatophyte T. rubrum and the favourable outcome of the brain lesion with itraconazole. CONCLUSION: Dermatophytic disease is rare, often severe. Our case is original because of the occurrence of a cerebral localization with good response to itraconazole and its mechanism of action deserves to be elucidated.

[Hypertension in scleroderma: A vital emergency]. / L'HTA au cours de la sclérodermie systémique : une urgence vitale.

PURPOSE: In systemic sclerosis, hypertension is feared because it is often heralding severe renal impairment. The objective of our study was to identify the frequency of arterial hypertension and clarify its etiologies in this condition. PATIENTS/METHODS: Our study was prospective. From January 2008 to May 2012, we have included all patients over the age of 16 years which featured a systemic scleroderma meeting the criteria for classification of Leroy and Medsger modified. Blood pressure was systematic and hypertension was defined as a greater than 140/90 mmHg PAS/PAD. RESULTS: We have collected 60 patients. It was 50 women and 10 men with an average age of 41.1 ans ± 13.03. Arterial hypertension was noted in sixteen patients (26.7%) with an average age of 48.8 years ± 13.21. It was nine diffuse cutaneous systemic scleroderma of six limited cutaneous scleroderma and one case of scleroderma sine scleroderma. Etiologic research hypertension had concluded to a renal cause in 12 patients. It was five scleroderma renal crisis (SRC), three vascular nephropathies, four chronic kidney failure (CKD) including three terminals and a moderate CKD. An 'essential' so-called HTA was observed in four patients. Hypertension was a major sign that reported five cases of SRC. These patients had received treatment anti hypertensive and renal extra cleansing. DISCUSSION: Hypertension is common in systemic scleroderma. Our data approximates of literature when its frequency and severity. CONCLUSION: Hypertension is a major warning sign that under no circumstances should overlook it or novo or secondary aggravation. Its support must be very early under penalty to put at stake the life-threatening in particular during the CRS.

The 2009-2010 H1N1 vaccination campaign for patients with egg allergy in a region of France.

We describe our experience of the influenza H1N1 vaccination in patients with egg allergy. All patients tolerated the vaccination in a simple or double dose protocol without any significant allergic reaction in this series.

[Immunological abnormalities in myelodysplastic syndromes. Prospective study (series of 40 patients)]. / Manifestations immunes associées aux syndromes myélodysplasiques. Etude prospective de 40 patients.

UNLABELLED: The association of myelodysplastic syndromes (MDS) with auto-immune diseases and humoral disorders have already been reported. In this prospective study we tried to estimate type and the frequency of immunological associated diseases among patients affected by MDS. PATIENTS-METHODS: In this prospective study, auto-immune disease and humoral immunity disorders were systematically searched during MDS and conversely MDS searched during cytopenia. All MDS secondary to chemotherapy and the children's MDS were excluded. The MDS diagnosis was established according to FAB criteria and patients were classified in two groups A or B according to presence (group A) or not (group B) of dysimmune manifestations. RESULTS: Forty patients(19 males and 21 females, mean age of 56,6 years) with MDS have been enrolled during this period (group A: 20 patients). Associated diseases are following: systemic lupus erythematosus (three), lupus-like syndrome(one), sarcoidisis(one), Sjogrën syndrome(one), polyarthritis (two), chronic liver diseases (three), autoimmune thyroid diseases (two), pyoderma gangrenosum (one), Crohn's disease(one), haemolytic anaemia (one), and pericardial effusion(one). CONCLUSION: A wide spectrum of auto-immune manifestations is frequently reported in myelodysplastic syndromes. Further studies are necessary for discuss the current physiopathological hypothesis with their therapeutic relevance.

Expression of transcription factor c-Rel and apoptosis occurrence in polydactylous and syndactylous limb buds of the talpid3 mutant chick embryo.

The chicken proto-oncogene c-rel encodes a transcription factor of the Rel/NF-kappa B family. We have previously shown that c-rel mRNAs accumulate in different types of apoptotic cells of the chick embryo, especially in mesenchymal cells within the four cell death areas of the limb bud: the anterior and posterior necrotic zones, the opaque patch and the interdigital necrotic zones. This study aimed to further establish the involvement of c-Rel in apoptosis of the developing limb by investigating its expression in the talpid3 mutant which was originally shown to be defective in apoptosis. However, our preliminary examinations highlighted the apparent presence of apoptotic cells in talpid3 embryos. Hence, we performed a systematic study of the occurrence of apoptosis in mutant and control embryos by the TUNEL method. The results revealed that apoptosis does occur in talpid3 embryos but with altered spatial and temporal patterns. This suggests that the talpid3 mutation does not affect a gene involved in apoptosis per se but rather in the determination of the pattern of apoptosis. Neither the expression of c-Rel nor that of its I kappa B alpha inhibitor are grossly modified in talpid3 limb buds, suggesting that the talpid3 mutation does not affect any of these genes. They are mostly expressed in epidermal, endodermal and striated muscle cells in control and in talpid3 limb buds as well. C-Rel was also detected in some scarce mesenchymal cells that could be apoptotic, in both control and mutant embryos. The only slight difference between control and talpid3 limbs lies in the perichondrium which is not fully differentiated in talpid3 embryos: c-Rel and I kappa B alpha are only faintly expressed in talpid3 perichondrial cells, whereas they are both detected in control perichondrial cells. Taken together, these results suggest that c-Rel could participate in several developmental processes, especially in the differentiation of perichondrial cells, besides its already documented involvement in apoptosis and haematopoeisis.

The avian transcription factor c-Rel is expressed in lymphocyte precursor cells and antigen-presenting cells during thymus development.

Transcription factors of the Rel/NF-kappaB family are widely involved in the immune system. In this study, we investigate the in vivo expression of the avian protein c-Rel in the T-cell lineage during thymus development. The majority of thymocytes do not express the c-Rel protein. However, lymphocyte precursor cells that colonize the thymus express the c-Rel protein shortly after their homing in the organ and before they begin to differentiate. c-Rel is also detected in different subsets of antigen-presenting cells such as epithelial cells, dendritic cells, and macrophages. In vitro studies have shown that Rel/NF-kappaB proteins are sequestered in an inactive form in the cytoplasm by interaction with the IkappaBalpha inhibitory protein. By immunocytochemistry, we show that in vivo c-Rel is localized in the cytoplasm of antigen-presenting cells but in both the cytoplasm and nucleus of lymphocyte precursor cells. The cytoplasmic localization of c-Rel in antigen-presenting cells correlates with a high expression of IkappaBalpha, whereas the nuclear localization of c-Rel in lymphocyte precursor cells correlates with a much lower expression of IkappaBalpha. These results suggest that c-Rel might be constitutively activated in lymphocyte precursor cells.

H19 overexpression in breast adenocarcinoma stromal cells is associated with tumor values and steroid receptor status but independent of p53 and Ki-67 expression.

In a previous study we described the expression of the H19 gene by in situ hybridization (ISH) in normal breast and in benign or malignant breast tumors (Dugimont T, Curgy JJ, Wernert N, Delobelle A, Raes MB, Joubel A, Stehelin D, Coll J: Biol Cell 1995, 85:117-124). In the present work, 1) we extend the previous one to a statistically useful number of adenocarcinomas, including 10 subclasses, 2) we provide information on the precise ISH localization of the H19 RNA by using, on serial tissue sections, antibodies delineating specifically the stromal or the epithelial component of the breast, and 3) we consider relationships between the H19 gene expression and various clinicopathological information as tumor values (T0 to T4), grades, steroid receptors, lymph node status, and molecular features as the p53 gene product and the Ki-67/MIB1 protein, which is specific to proliferating cells. Data indicate that 1) in 72.5% of studied breast adenocarcinomas an overall H19 gene expression is increased when compared with healthy tissues, 2) the H19 gene is generally overexpressed in stromal cells (92.2%) and rarely in epithelial cells (2.9% only), 3) an up-regulation of the H19 gene is significantly correlated with the tumor values and the presence of both estrogen and progesterone receptors, and 4) at the cellular level, the H19 gene demonstrates an independent expression versus accumulation of both the p53 protein and the Ki-67/MIB-1 cell-cycle marker.

The avian transcription factor c-Rel is induced and translocates into the nucleus of thymocytes undergoing apoptosis.

This study investigates the involvement of the avian transcription factor c-Rel in thymocyte apoptosis occurring either in vivo or in organotypic culture. In vivo, only a few cortical thymocytes express the c-Rel protein. Their number, localization and morphology resemble that of apoptotic cells evidenced by TUNEL staining. In organotypic culture, the expression of c-Rel is induced in medullary thymocytes as apoptosis is triggered. This induction would be post-transcriptional since no increase in the c-rel gene expression is detected. Moreover, c-Rel translocates into the nucleus of medullary thymocytes during the time course of apoptosis. This translocation is preceded by a decrease in ikba expression, the gene which encodes the avian homologue of IkappaBalpha. Altogether these results suggest that the proto-oncogene c-rel could take an active part in apoptosis of cortical thymocytes occurring in vivo during T-cell selection as well as in experimentally-induced apoptosis of medullary thymocytes.

Stromal expression of c-Ets1 transcription factor correlates with tumor invasion.

The stroma reaction has an important role in tumor growth, invasion, and metastasis. In various invasive human carcinomas, as well as in a mouse model for tumor invasion, transcripts encoding the transcription factor c-Ets1 were detected within stromal fibroblasts, whereas they were absent in epithelial tumor cells. This expression of c-Ets1 was often increased in fibroblasts directly adjacent to neoplastic cells. Endothelial cells of stromal capillaries were also positive for c-Ets1 expression. In contrast, fibroblasts of corresponding noninvasive lesions and of normal tissues were consistently negative. In cultured human fibroblasts stimulated by basic fibroblast growth factor and tumor necrosis factor alpha, the expression of c-Ets1 correlated with the accumulation of transcripts for potential target genes, collagenase-1 and stromelysin-1. The same correlation was observed in some of the invasive carcinomas investigated. These results suggest that c-Ets1 participates in the regulation of tumor invasion in vivo.

High levels of c-rel expression are associated with programmed cell death in the developing avian embryo and in bone marrow cells in vitro.

To determine the physiological processes in which the transcription factor c-Rel may act, we have examined its pattern of expression in the avian embryo by in situ hybridization. These studies showed that c-rel is expressed ubiquitously at low levels and at high levels in isolated cells undergoing programmed cell death by apoptosis or autophagocytosis. To further establish a functional link between expression of c-rel and cell death, we examined the biological consequences of c-rel overexpression in vitro. In primary avian fibroblasts, overexpression of c-rel leads to transformation and dramatic life span extension. In contrast, bone marrow cells expressing high levels of c-rel undergo a process of programmed cell death displaying features of both apoptosis and autophagocytic cell death. Thus, these experiments suggest a critical role for c-rel not only in the control of cell proliferation, but also in the induction of cell death.