Bax, bcl-2 and c-kit expression in non-small-cell lung cancer and their effects on prognosis.

In non-small-cell lung cancer (NSCLC), stage of the disease is still the most important prognostic factor. Other than stage, many biological markers and many other prognostic factors are studied to define their effects on prognosis of lung cancer. In this study, we aimed to evaluate the expressions of Bax and bcl-2 genes which are important in apoptosis and c-kit, which is a tyrosine kinase transmembrane receptor, as well as searched their response to treatment modalities and effects on survival. Sixty-nine NSCLC cases' pathological samples were stained with specific Bax, bcl-2 and c-kit dyes by immunohistochemical (IHC) methods. IHC evaluation was done by the semichantitative method according to the distribution and intensity of the staining. Twelve of 69 cases (17.4%) were stage I, 28 (40.5%) were stage II, 17 were (24.6%) stage IIIA, nine cases were (13.1%) stage IIIB and three cases (4.4%) were stage IV patients. Their histological subtypes were as follows: of 69 cases, 36 (52.2%) were squamous cell carcinoma, 28 (40.6%) were adenocarcinoma, five (7.2%) were adenosquamous cell carcinoma (two patients) and large-cell carcinoma (three patients). The positive immunostaining rates for Bax and bcl-2 in whole group, squamous cell carcinoma and adenocarcinoma groups were 40.6%/36.2%, 55.6/69.4% and 25.0/0.0%, respectively. The positive immune staining rates for c-kit in whole group, squamous cell carcinoma and adenocarcinoma groups were 7.2, 5.6 and 7.1%, respectively. We didn't find any correlation with Bax, bcl-2 and c-kit expressions and clinicopathological parameters such as age, tumour size, lymph node involvement, smoking, stage of the disease, response to radiotherapy and chemotherapy. Results are interpreted according to survival; bax and bcl-2 expressions were not so effective both in whole group and histologically subgrouped patients. C-kit expression was also found not related with survival in whole group whereas found as a bad prognostic factor in patients with squamous cell carcinoma. These findings could indicate that the expression of apoptotic pathway markers and c-kit may have a role in the prognosis of early stage NSCLC, especially with squamous cell carcinoma subtype.

Antithrombin III pretreatment reduces neutrophil recruitment into the lung and skeletal muscle tissues in the rat model of bilateral lower limb ischemia and reperfusion: a pilot study.

BACKGROUND: Anti-inflammatory action of Antithrombin III (AT III) is still not well understood in ischemia/reperfusion (I/R) injury. In the present study, we aimed to investigate the anti-inflammatory action of AT III on remote lung and local skeletal muscle tissue injury in a rat model of bilateral lower limb I/R model. METHODS: Bilateral lower limb ischemia and reperfusion were produced by means of tourniquets occlusions and releases, respectively. Three groups of rats were used in this controlled study: sham group (sham, n=3) underwent 5 h of anesthesia only; control group (I/R, n=7) underwent 3 h of bilateral lower limb ischemia followed by 2 h of reperfusion; and AT III pretreated group (I/R-AT III, n=6) underwent the same procedure as the control group, but also received i.v. 250 U kg-1 AT III 30 min before ischemia induction under midazolam and fentanyl anesthesia. MEASUREMENTS AND RESULTS: Lung and muscle tissue accumulation of polymorphonuclear leukocytes (PMN) were assessed by measuring tissue myeloperoxidase (MPO) activity. Histopathological changes in tissues were assessed by PMN counts in the lung, and muscle tissues and by histological lung injury score. Plasma 6-keto prostaglandin F(1alpha) and tumor necrosis factor alpha levels were measured by an enzyme immunoassay technique. Myeloperoxidase activity could not be detected in the muscle tissues of all groups. The lung and muscle tissue PMN counts in the I/R group were significantly higher compared with the I/R-AT III group (P<0.05). CONCLUSIONS: Data from the present study provides some evidence that AT III pretreatment attenuates remote lung and local skeletal muscle tissue injury caused by lower limb I/R.

Antithrombin III pretreatment reduces neutrophil recruitment into the lung in a rat model of abdominal sepsis.

BACKGROUND: Antithrombin III (AT III) is a serine protease inhibitor and the mechanism of its anti-inflammatory action is still not understood. In the present study, we aimed to investigate the anti-inflammatory action of AT III on lung injury in a rat model of sepsis. METHODS: Three groups of animals were used in this controlled study: the sham-operated group (sham, n = 3) which only underwent a laparotomy; the control group (control, n = 7) which underwent cecal ligation and perforation (CLP); and the AT III-treated group (AT III, n = 6) which underwent CLP and received intravenous (i.v.) 250 U/kg AT III 30 min before induction of sepsis. Rats were killed 24 h after induction of sepsis by needle aspiration of the right ventricle after a sternotomy, and the lungs and trachea were removed en bloc under ether anesthesia. RESULTS: Pulmonary accumulation of polymorphonuclear leukocytes (PMN) was assessed by measuring lung tissue myeloperoxidase (MPO) activity. Lipid peroxidation in lung tissue was assessed by tissue thiobarbituric acid reactive substance (TBARS) levels. The plasma prostacyclin level was assessed by the plasma 6-keto prostaglandin F(1alpha)(6-keto-PGF(1alpha)) level, which is a stable derivative of prostacyclin. Histopathological changes in lung tissue were assessed by PMN count in the capillaries and alveolar spaces. The lung tissue TBARS level, MPO activity and PMN count in the control group were significantly higher than in the AT III group (P < 0.05). The change in plasma 6-keto-PGF(1alpha) level in the AT III group was insignificant compared with the control group (P = 0.15). CONCLUSIONS: AT III prevented pulmonary infiltration of PMN and subsequent injury by the endothelial release of prostacyclin in CLP-induced sepsis.

Testis fixation in prepubertal rats: fibrin glue versus transparenchymal sutures reduces testicular damage.

Experimental studies have shown that different suture materials used in testis fixation cause some degree of inflammation in the testis. This study was planned to compare the histological changes that were caused by fibrin glue which is a tissue sealant and by silk and polypropylene for transparenchymal testis fixation. 28 prepubertal rats were divided into 4 groups. Testis was fixed to the tunica vaginalis by fibrin glue in group 1, by silk in group 2 and by polypropylene in group 3. Group 4 was planned as a control. Testicular inflammation and seminiferous tubular diameter were evaluated for histological changes. The least inflammation was observed in the fibrin glue group, while the most inflammation occurred in the silk group. Seminiferous tubular diameter was 241.55 +/- 45.90 in the fibrin glue group, 151.90 +/- 8.34 in the silk group and 161.36 +/- 9.96 in the polypropylene group. In conclusion, fibrin glue, when used for testis fixation, causes less inflammation and less destruction of seminiferous tubular diameter compared with silk and polypropylene.

Does sucralfate prevent apoptosis occurring in the ischemia/reperfusion-induced intestinal injury?

BACKGROUND/PURPOSE: We have shown in a previous study that sucralfate is beneficial in the prophylaxis and treatment of hypoxia/reoxygenation-induced intestinal injury. The aim of this study is to investigate whether sucralfate has any effect on the prevention of apoptosis in the ischemia/reperfusion (I/R)-induced intestinal injury. METHODS: Rats were randomized into three groups. Group 1 and 2 were subjected to I/R. Group 1 (treatment group) received sucralfate while group 2 (treatment control group) did not. Group 3 served as a normal control group (sham group). The terminal ileum was harvested for histopathologic investigation by light microscopy. The presence of apoptotic enterocytes (DNA fragmentation in cell nuclei) was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL) reaction. RESULTS: In treatment control group, 3 of 7 rats had severe inflammation. None of the sucralfate-treated rats showed severe inflammation, 6 of them only showed mild inflammatory changes (p < 0.05). The apoptotic percentage was found to be 37.1 +/- 9.4 in the sucralfate-treated group (group 1), whereas it was 45.4 +/- 3.9 in the untreated group (group 2) (p < 0.05). The sham group had a completely normal intestinal architecture. CONCLUSIONS: The present study shows that 1) the experimental model of I/R-induced intestinal injury induces enterocyte apoptosis; 2) sucralfate decreases enterocyte apoptosis in the experimental model of I/R-induced intestinal injury which may play a key role in the pathophysiological events leading to failure of the intrinsic gut barrier defense mechanisms.

Effect of heparin on tendon degeneration: an experimental study on rats.

This study investigated the local effects of heparin on locally administered corticosteroid-induced experimental Achilles tendinitis. After performing Achilles degeneration, 28 rats were divided into two groups; one was treated with local heparin and the other with saline injections at 3 and 6-day intervals. The tendons and paratenons were excised after 60 or 75 days and evaluated histopathologically and statistically. Heparin-injected tendons and paratenons demonstrated significantly higher scores for most compared groups, thus worsening the degeneration. At the second part of the research, eight healthy tendons were injected with heparin at 3-day intervals for 1 month, and seven of them showed various degrees of degeneration. Heparin itself thus has a degenerative effect on the tendon and should not be used in the treatment of Achilles tendon degeneration.