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Objective: Mast cells (MCs) have been proved to be multifunctional cells which are known to be located at peri-and intra-tumoral sites, playing an active role physiologically or pathologically. In humans, MCs are subtyped by the difference in their neutral protease content. MCs that have granules containing tryptase alone (MCT) are predominantly found at mucosal sites. MCs whose granules possess tryptase along with chymase (MCTC) are found especially within connective tissue. MC mediators have different functions and the coexistence of both MC subtypes contributes to tissue homeostasis. Furthermore, cyclooxygenase-2 (COX-2) is an enzyme associated with inflammation, cell growth and differentiation, prevention of apoptosis and tumorigenesis. Recent studies show the clinical significance of COX-2 expression in different tumor types. However, to our knowledge, there is no data assessing the relationship between COX-2 and MC density in uterine leiomyomas. We aimed to investigate the relation between the expression of COX-2, MC density, and proportional changes of MC phenotypes in human leiomyoma uteri and control cases, and also their possible correlations between each other. Methods:We performed a retrospective study of 34 cases carried out on parafin-embedded samples obtained from 14 control (group 1) and 20 leiomyoma uteri (group 2) patients who had undergone curative hysterectomy. These specimens were investigated immunohistochemically by using anti-cyclooxygenase-2 (COX-2) antibodies to stain COX-2; anti-tryptase antibodies to stain MCT and anti-chymase antibodies to stain MCTC.Results: In leiomyoma, the median value of COX-2 staining grade was 2 (min:1-max:3) which was statistically lower than that of controls with a median value of 3 (min:2-max:4) (p=0.001). The median value of tryptase expression was 12 (min:10-max:16) in the control myometrium, slightly higher than that of the leiomyoma group which had a median value of 10.5 (min:6-max:15). On the other hand, the median value of chymase expression was 7 (min:4-max:13) in the control myometrium, which was significantly higher (p=0.001) than that of the leiomyoma group with a median value of 5 (min:2-max:8). Thus, in the leiomyoma group, the mast cell subtypes, including tryptase÷chymase proportion, was found to be significantly higher than the controls (p=0.032). Moreover, COX-2, tryptase and chymase expressions showed no correlation in both groups. Conclusion:This study has demonstrated that expressions of COX-2 and mast cell subtypes are reduced in leiomyoma, and the proportion of mast cell subtypes of MCT÷MCTC increases in leiomyoma compared to the control group. However, MC subtypes neither correlated with each other nor with COX-2 expression in the leiomyoma and control series. Understanding the mechanisms for MC functions and the secretory molecules will provide a basis for a rational approach to the development of antitumoral therapy in patients with leiomyoma and other tumors. (JAREM 2011; 1: 44-8) Key Words: Mast cells, tryptase, chymase,...
Objective: Mast cells (MCs) have been proved to be multifunctional cells which are known to be located at peri-and intra-tumoral sites, playing an active role physiologically or pathologically. In humans, MCs are subtyped by the difference in their neutral protease content. MCs that have granules containing tryptase alone (MCT) are predominantly found at mucosal sites. MCs whose granules possess tryptase along with chymase (MCTC) are found especially within connective tissue. MC mediators have different functions and the coexistence of both MC subtypes contributes to tissue homeostasis. Furthermore, cyclooxygenase-2 (COX-2) is an enzyme associated with inflammation, cell growth and differentiation, prevention of apoptosis and tumorigenesis. Recent studies show the clinical significance of COX-2 expression in different tumor types. However, to our knowledge, there is no data assessing the relationship between COX-2 and MC density in uterine leiomyomas. We aimed to investigate the relation between the expression of COX-2, MC density, and proportional changes of MC phenotypes in human leiomyoma uteri and control cases, and also their possible correlations between each other. Methods:We performed a retrospective study of 34 cases carried out on parafin-embedded samples obtained from 14 control (group 1) and 20 leiomyoma uteri (group 2) patients who had undergone curative hysterectomy. These specimens were investigated immunohistochemically by using anti-cyclooxygenase-2 (COX-2) antibodies to stain COX-2; anti-tryptase antibodies to stain MCT and anti-chymase antibodies to stain MCTC.Results: In leiomyoma, the median value of COX-2 staining grade was 2 (min:1-max:3) which was statistically lower than that of controls with a median value of 3 (min:2-max:4) (p=0.001). The median value of tryptase expression was 12 (min:10-max:16) in the control myometrium, slightly higher than that of the leiomyoma group which had a median value of 10.5 (min:6-max:15). On the other hand, the median value of chymase expression was 7 (min:4-max:13) in the control myometrium, which was significantly higher (p=0.001) than that of the leiomyoma group with a median value of 5 (min:2-max:8). Thus, in the leiomyoma group, the mast cell subtypes, including tryptase÷chymase proportion, was found to be significantly higher than the controls (p=0.032). Moreover, COX-2, tryptase and chymase expressions showed no correlation in both groups. Conclusion:This study has demonstrated that expressions of COX-2 and mast cell subtypes are reduced in leiomyoma, and the proportion of mast cell subtypes of MCT÷MCTC increases in leiomyoma compared to the control group. However, MC subtypes neither correlated with each other nor with COX-2 expression in the leiomyoma and control series. Understanding the mechanisms for MC functions and the secretory molecules will provide a basis for a rational approach to the development of antitumoral therapy in patients with leiomyoma and other tumors. (JAREM 2011; 1: 44-8) Key Words: Mast cells, tryptase, chymase,...
A AB BS ST TR RA AC CT T O Ob bj je ec ct ti iv ve e: : Angioneogenesis, which plays significant roles in a variety of physiological processes such as embryonic growth and wound healing, is strictly delimited and is finely tuned by a balance of proangiogenic and antiangiogenic factors. This study was conducted to investigate the angioneogenic effect of interleukin-8 (IL-8) administered intramuscularly. M Ma at te er ri ia al l a an nd d M Me et th ho od ds s: : Twelve New Zealand white rabbits were included in this study. A total daily dose of 4 micrograms (1 mcg/kg) of IL-8 was administered into the left (Group A) and saline solution into the right (Group B) gluteus maximus muscles of 6 rabbits for 6 days. The remaining 6 rabbits constituted the sham group (Group C). Gluteal muscle samples were obtained from injection sites in all groups and were stained with hematoxylin-eosin and immunohistochemically by using streptavidin biotin method with CD31 antibody. Avidin-biotin peroxidase method (LSAB) was used as secondary and binding antibody. Diaminobenzidine tetrahydrochloride (DAB) was used as chromogenic substance. In immunohistochemical staining with CD31, vascular channels covered with brown stained cells or cell clusters were considered and were counted as vascular network. R Re es su ul lt ts s: : Three subjects in Group A and one subject in Group B displayed findings of large muscle necrosis and regeneration. Vascular channel score was significantly higher in Group A (p=0.032) (Group A; median=12.5, min=6, max=16. Group B; median=5, min=4, max=13. Group C; median=4.5, min=4, max=13.) than in the other groups. C Co on nc cl lu us si io on n: : IL-8 chemokine family seems to stimulate angioneogenesis in rabbit skeletal muscles. This result is promising in terms of the possible therapeutic potential of IL-8. Daily administration at a dose of around 1 mcg/kg caused local tissue necrosis, hence use of alternative routes such as intraarterial administration must be investigated to avoid such complications. K Ke ey y W Wo or rd ds s: : Angioneogenesis; interleukin-8; skeletal muscle Ö ÖZ ZE ET T A Am ma aç ç: : Embriyonik büyüme ve yara iyileşmesi gibi bir dizi fizyolojik süreçte önemli rol oynayan anjiyogenez, proanjiyojenik ve antianjiyojenik faktörlerin birbirlerinden kesin çizgiler ile dengelenmesiyle ayrılmış ve hassas şekilde düzenlenmiştir. Bu çalışma, intramusküler olarak uygulanan interlökin-8 (IL-8)'in anjiyoneogenetik etkisini araştırmak için yapılmıştır. G Ge er re eç ç v ve e Y Yö ön nt te em ml le er r: : Çalışmada on iki adet Yeni Zelanda cinsi beyaz tavşan kullanıldı. Altı gün boyunca altı tavşanın sol gluteusuna 1 mcg/kg'dan toplam 4 mikrogram IL-8 (Grup A), sağ gluteusuna serum fizyolojik (Grup B) enjeksiyonu uygulandı. Diğer altı tavşan kontrol grubu idi (Grup C). Enjeksiyon uygulanan bölgelerden alınan gluteal kas örnekleri, Hemotoksilen-Eozin ve Streptavidin-biotin yöntemi kullanılarak CD31 antikoru ile immünohistokimyasal olarak boyandı. Avidin-biotin peroksidaz metodu (LSAB) ikincil ve bağla...
Mast cells are a subtype of white blood cells and are involved in the immune system. These cells contain many chemical substances called mediators, which are involved in the allergic response. The fact that mast cells play a role in many events that require urgent intervention, especially anaphylaxis, has led to a more detailed study of these cells. The diseases also caused by dysfunctions of mast cells have been examined in many circumstances. For instance, mast cell activation syndrome is known as an augmented number of cells due to decreased cell death, resulting in clinical symptoms affecting many systems. The main common symptoms include flushing, hypotension, urticaria, angioedema, headache, vomiting and diarrhea. Although the underlying mechanism is not yet clearly known, we aim to review the literature in a broad perspective and bring together the existing knowledge in the light of the literature due to the diversity of its involvement in the body and the fact that it is a little known syndrome.
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