Cagnur Ulukus

Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury

The cytokine erythropoietin (EPO) possesses potent neuroprotective activity against a variety of potential brain injuries, including transient ischemia and reperfusion. It is currently unknown whether EPO will also ameliorate spinal cord injury. Immunocytochemistry performed using human spinal cord sections showed abundant EPO receptor immunoreactivity of capillaries, especially in white matter, and motor neurons within the ventral horn. We used a transient global spinal ischemia model in rabbits to test whether exogenous EPO can cross the blood–spinal cord barrier and protect these motor neurons. Spinal cord ischemia was produced in rabbits by occlusion of the abdominal aorta for 20 min, followed by saline or recombinant human (rHu)-EPO (350, 800, or 1,000 units/kg of body weight) administered intravenously immediately after the onset of reperfusion. The functional neurological status of animals was better for rHu-EPO-treated animals 1 h after recovery from anesthesia, and improved dramatically over the next 48 h. In contrast, saline-treated animals exhibited a poorer neurological score at 1 h and did not significantly improve. Histopathological examination of the affected spinal cord revealed widespread motor neuron injury associated with positive terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling in control but not in rHu-EPO-treated animals. These observations suggest both an acute as well as a delayed beneficial action of rHu-EPO in ischemic spinal cord injury. Because rHu-EPO is currently used widely with an excellent safety profile, clinical trials evaluating its potential to prevent motor neuron apoptosis and the neurological deficits that occur as a consequence of ischemic injury are warranted.

Neuroprotective Effect of Erythropoietin on Hypoxic-Ischemic Brain Injury in Neonatal Rats

Erythropoietin (Epo) prevents ischemia and hypoxia-induced neuronal death in vitro. Recent studies have shown that this cytokine also has in vivo neuroprotective effects in cerebral and spinal ischemia in adult rodents. In this study, we aimed to investigate the effect of systemically administered recombinant human Epo on infarct volume and apoptotic neuronal death in a newborn rat hypoxic-ischemic brain injury model. Our results showed that a single dose of intraperitoneal Epo treatment (1,000 U/kg) significantly decreased the mean infarct volume as compared to the control group. In contrast to the Epo-treated group, histopathological examination by positive terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling of the affected brain in control animals revealed widespread neuronal injury associated with numerous apoptotic cells. Morphometric analysis to determine the extent of damage quantitatively ascertained that the mean infarct volume was significantly lower in the Epo-treated group (p < 0.003). These results suggest the beneficial neuroprotective effect of Epo in this model of neonatal hypoxic-ischemic brain injury. To our knowledge, this is the first study that demonstrates a protective effect of Epo against hypoxia-ischemia in the developing brain.

Effect of laparoscopic excision of endometriomas on ovarian reserve: serial changes in the serum antimüllerian hormone levels.

OBJECTIVE To investigate the effect of laparoscopic endometrioma stripping on serum antimüllerian hormone (AMH) and the correlation between the clinicopathologic factors. DESIGN Prospective study. SETTING University hospital. PATIENT(S) Sixty-five women with endometriomas. INTERVENTION(S) All patients underwent laparoscopic cystectomy. Serum AMH, FSH, LH, E(2), and antral follicle count (AFC) were measured preoperatively, at 6 weeks, and at 6 months postoperatively. Specimens were analyzed histopathologically. MAIN OUTCOME MEASURE(S) The primary end point was to assess the ovarian reserve damage based on alterations of AMH and the secondary end point was to detect the changes in FSH, LH, E(2), and AFC. RESULT(S) Serum AMH decreased significantly at the sixth month (61%) postoperatively. The FSH level increased significantly at the sixth week, but returned to normal at the sixth month. The AFC increased significantly at the sixth week and at the sixth month. The AMH level decrease was more evident in patients with the cyst <5 cm (65.7% vs. 41.3%). The AMH decrease was more in bilateral compared with unilateral endometriomas (67% versus 57%, respectively). No correlation was detected between the histopathologic analyses and tAMH level. Initially the AMH level was the only independent factor affecting the AMH decrease (odds ratio, 3.68; 95% confidence interval 1.66-8.14). CONCLUSION(S) Laparoscopic cystectomy of ovarian endometriomas causes a significant and progressive decline in serum AMH levels.

The protective effects of carnosine and melatonin in ischemia-reperfusion injury in the rat liver.

The reperfusion following liver ischemia results in hepatocyte damage and apoptosis. The aim of this study was to investigate the effects of two antioxidant agents, carnosine and melatonin, in rat liver ischemia-reperfusion injury. Five study groups were formed; I. sham, II. ischemia-reperfusion, III. ischemia-reperfusion+melatonin, IV. ischemia-reperfusion+carnosine, V. ischemia-reperfusion+melatonin+carnosine. Then 250 mg/kg carnosine and 10 mg/kg melatonin were administered intraperitoneally 30 min before ischemia and immediately after the reperfusion. Sinusoidal dilatation, congestion and neutrophil infiltration were observed in the ischemia-reperfusion group while these symptoms were less pronounced in the treatment groups. Alanine aminotransferase, aspartate aminotransferase and myeloperoxidase levels were increased in the ischemia-reperfusion group while they were lowered in the treatment groups. Glutathione level was low in the ischemia-reperfusion group while it tended to increase in the ischemia-reperfusion+carnosine administered and ischemia-reperfusion+carnosine+melatonin administered groups. There was an increase in the number of apoptotic cells in the ischemia-reperfusion group while this number was lowered in the treatment groups. Carnosine was more effective than melatonin in the reversal of structural and biochemical alterations that resulted from ischemia-reperfusion injury. The administration of melatonin and carnosine together yielded better outcomes compared to the sole administration of each agent.

HGF/c-Met Overexpressions, but not Met Mutation, Correlates with Progression of Non-small Cell Lung Cancer

Hepatocyte Growth Factor (HGF) and its receptor c-Met are suggested to play an important role in progression of solid organ tumors by mediating cell motility, invasion and metastasis. Overexpression of HGF and c-Met have been shown in non-small-cell lung cancer (NSCLC). However, their role in tumor progression is not clearly defined. The aim of this study is to determine the role of HGF/c-Met pathway and its association with invasion related markers and clinicopathologic parameters in NSCLC. Immunohistochemical analysis was performed on 63 paraffin-embedded NSCLC tumor sections. The expressions of invasion related markers such as Matrix Metalloproteinases (MMPs) 2 and 9, Tissue Inhibitor Metalloproteinase (TIMP) 1 and 3 and RhoA were also examined. Co-expression of HGF/c-Met was significantly associated with lymph node invasion and TIMP-3 and RhoA overexpressions. There were positive correlation between TIMP-3 overexpression and advanced stage and negative correlation between RhoA overexpression and survival. DNA sequencing for Met mutations in both nonkinase and tyrosine kinase (TK) domain was established. A single nucleotide polymorphism (SNP) in sema domain and two SNPs in TK domain of c-Met were found. There was no statistically significant correlation between the presence of c-Met alterations and clinicopathologic parameters except shorter survival time in cases with two SNPs in TK domain. These results suggest that HGF/c-Met might exert their effects in tumor progression in association with RhoA and probably with TIMP-3. The blockade of the HGF/c-Met pathway with RhoA and/or TIMP-3 inhibitors may be an effective therapeutic target for NSCLC treatment.

The effect of apoptotic activity, survivin, Ki-67, and P-glycoprotein expression on prognosis in pancreatic carcinoma.

Objectives: The pathogenetic mechanisms that regulate the aggressive behavior of pancreatic cancer still remain to be clarified. Alterations in the apoptotic pathway and proliferative activity of tumor cells as well as mechanisms contributing to the intrinsic drug resistance of pancreatic tumors have been investigated. Survivin is a recently described antiapoptotic protein, which, when overexpressed, is associated with worse prognosis in a majority of tumors. P-glycoprotein, a product of multidrug resistance gene-1 (MDR-1) was reported to be expressed in drug-resistant tumors. The purpose of this study was to investigate whether apoptosis, its regulation by survivin, tumor cell proliferation, and P-glycoprotein expression have a significant role on the biologic behavior of pancreatic adenocarcinoma. Methods: Tumors of 45 patients with pancreatic adenocarcinoma were studied for the detection of survivin, P-glycoprotein, and Ki-67 expression by immunohistochemical method and apoptotic index by TUNEL method. Immunohistochemical staining was scored and Ki-67 and apoptotic indices were expressed as percentage of stained cells. Results: Immunohistochemistry for survivin and P-glycoprotein revealed positive staining in 7 (15.4%) and 36 (79.5%) of the 45 tumors, respectively. The mean Ki-67 proliferative index was 43.75 ± 25.30%. The mean apoptotic index evaluated with the TUNEL method was 37.12 ± 34.55% for the whole group. We found no significant association between apoptotic index, expressions of survivin and P-glycoprotein, and clinicopathologic variables and survival. Conclusions: Apoptotic activity, survivin, and P-glycoprotein expression failed to predict the disease extent and biologic behavior in pancreatic adenocarcinoma in our cases.

Rapid tumor lysis syndrome in a patient with metastatic colon cancer as a complication of treatment with 5-fluorouracil/leucoverin and irinotecan

Tumor lysis syndrome is a potentially fatal complication of anticancer therapy that is usually seen in patients with bulky, rapidly proliferating, treatment-sensitive tumors such as hematological malignancies, but it rarely occurs in a variety of solid tumors such as colorectal carcinoma. Combination chemotherapy with infusional 5-fluorouracil/leucoverin and irinotecan has been recently accepted as the first treatment option for metastatic colorectal cancer. We present a case of tumor lysis syndrome in a patient with metastatic colon carcinoma that occurred 72 hrs after the initial course of a combination chemotherapy with irinotecan and 5-fluorouracil/leucoverin. Despite the immediate treatment with aggressive hydration by a sodium bicarbonate infusion, followed by forced diuresis and uricolytic therapy, he died of a sudden cardiac arrest complicated by acute renal failure. Our case indicates that administration of 5-fluorouracil/leucoverin and irinotecan for bulky tumors of colorectal origin with a rapid doubling time may induce an acute tumor lysis syndrome, which necessitates frequent laboratory monitoring and a close follow-up of the patient as well as prompt initiation of appropriate therapeutic measures.

Expression of Bcl-2, Bax and p53 proteins in pituitary adenomas an immunohistochemical study

Aims and Background Although pituitary adenomas are usually benign lesions, their growth rate is highly variable and unpredictable. Apoptosis appears to be an important process in neoplastic lesions. The purpose of this study was to investigate the expression of apoptosis-related proteins including Bcl-2, bax and p53 in pituitary adenomas and its correlation with hormone function, tumor size, local control, and proliferative activity. Study Design The expression of Bcl-2, Bax and p53 proteins and hormonal function were determined in formalin-fixed, paraffin-embedded tissue from 41 untreated pituitary adenomas using immunohistochemistry. The patients were followed for a median of 60 months (range, 12 to 95). Patient charts were reviewed to record tumor recurrence and size. Tumor proliferative activity was assessed by immunohistochemistry using Ki-67 antibody. Results Of 41 pituitary adenomas, 26 (63%) were hormone-secreting and 15 (37%) non-functioning, 34 (83%) were macroadenoma and 7 (17%) microadenoma, and 15 (37%) showed local relapse. Six (14%) adenomas were of low proliferative activity, whereas the others (86%) were non-proliferative. Immunohistochemically, 31 adenomas (75%) showed bcl-2 positivity, 37 (90%) bax positivity, and 7 (17%) p53 positivity. Statistical analysis revealed that Bcl-2 protein expression significantly diminished in prolactin-secreting and non-functioning adenomas (P = 0.005 and P = 0.006, respectively), and increased in growth hormone-secreting adenomas (P = 0.003). In addition, expression of bax protein significantly decreased in recurrent tumors, in contrast to p53 protein, which showed a significant increase (P = 0.03 and P = 0.002, respectively). Conclusions We think that apoptosis-related proteins such as Bcl-2, Bax and p53 may be significantly related to hormone function and local control in pituitary adenomas.

Collision tumor: serous cystadenocarcinoma and dermoid cyst in the same ovary

IntroductionCollision tumor means the coexistence of two adjacent, but histologically distinct tumors without histologic admixture in the same tissue or organ. Collision tumors involving ovaries are extremely rare.CaseWe present a case of 45-year-old parous woman with a left dermoid cyst, with unusual imaging findings, massive ascites and peritoneal carcinomatosis. The patient underwent cytoreductive surgery. The histopathology revealed a collision tumor consisting of an invasive serous cystadenocarcinoma and a dermoid cyst.

Angioma serpiginosum: Dermoscopy for diagnosis, pulsed dye laser for treatment

Angioma serpiginosum is a rare benign vascular disorder, characterized clinically by multiple minute, red to purple, grouped macules in serpiginous and gyrate patterns and histopathologically by ectatic dilatation of capillaries. Patients can undergo unnecessary hematological tests, because the condition can be confused with chronic purpuric dermatoses. An 18‐year‐old man with angioma serpiginosum of his left arm was evaluated by dermoscopy and treated with pulsed dye laser. Numerous small, relatively well‐demarcated, round to oval red lagoons were determined with dermoscopy, and approximately 75% of the area of his lesion disappeared after four sessions of pulsed dye laser. Our case supports the hypothesis that dermoscopy is beneficial in the diagnosis of angioma serpiginosum and that pulsed dye laser is effective in the treatment of this disorder.