Ahmet Balik

The association of the expression of miR-122-5p and its target ADAM10 with human breast cancer

MicroRNAs can regulate many biological functions. miR-122-5p has a tumor suppressor function through different molecular pathways. Also, our second hit, ADAM10, targeted by miR-122-5p, is a major determinant of HER2 shedding causing that trastuzumab cannot bind to HER2 receptors. Therefore, our analysis upon ADAM10 expression and miR-122-5p was a good point to understand molecular mechanism of breast cancer. In our study, we investigated the expression profiles of miR-122-5p and its target ADAM10 in 71 breast cancer patients. Immunohistochemical analysis of ER, PR and HER2 gene products was used to categorize tumors in patients. Expression data and immunohistochemical findings were evaluated to comment on the relationship between miR-122-5p and ADAM10. ADAM10 expression was higher in tumor than that of normal tissue but miR-122-5p expression was lower in tumor than that of normal tissue. The expression pattern in HER2+ patients was reverse of the overall result. It can be explained like that miR-122-5p expression increases especially in HER2+ cancer cell to suppress ADAM10 shedding activity on HER2 receptor. However, increase in expression of tumor suppressor miR-122-5p is not enough to inhibit ADAM10. All in all, we can think miR-122-5p as potential regulator of ADAM10 and trastuzumab resistance. Since if we increase miR-122-5p activity together with trastuzumab administration, then HER2+ breast cancer cells may overcome trastuzumab resistance by inhibiting ADAM10 shedding activity on HER2 receptors and increase the efficiency of trastuzumab.

Spontaneous rupture of the spleen in secondary amyloidosis: A patient with rheumatoid arthritis

A 63-year-old man who had had a history of rheumatoid arthritis presented with shock and hemoperitoneum, without a history of trauma. An emergency laparatomy revealed hemoperitoneum and splenic rupture with massive bleeding. Splenectomy was performed. Histopathological examination of the spleen revealed amyloid deposition in the wall of the vessels. Rectal biopsy revealed amyloid deposition in mucosa that indicating amyloidosis was systemic. Histochemical studies showed that amyloid was secondary or AA.

Gastric and prostate adenocarcinoma in a patient with metastatic gastrointestinal stromal tumor.

Background: Gastrointestinal stromal tumor (GIST) is the most common mesenchymal malignancy of the gastrointestinal tract. Gastric cancer is the second most common neoplasm worldwide. Prostate cancer is the most common non-cutaneous cancer. The most frequently encountered second malignancies in patients with prostate adenocarcinoma include carcinomas of the bladder, stomach, and colon, followed by cutaneous and hematolymphoid malignancies. Case Report: We report the case of a 60-year-old male patient who was diagnosed with GIST and started on imatinib mesylate 400 mg/day. 2 years later, the patient was diagnosed with gastric adenocarcinoma, and a subtotal gastrectomy and gastrojejunostomy were performed. At followup 6 months later, prostate-specific antigen (PSA) levels were elevated, and a prostate biopsy showed a prostate adenocarcinoma. Conclusion: This is the second report of metachronous prostate cancer, gastric cancer, and GIST in the English language literature.

EXTRAVISCERAL PRIMARY HYDATID CYST OF THE RETROPERITONEUM

Background:  Hydatid cyst (HC) continues to be endemic in the Mediterranean countries, such as Turkey. Living in a rural area is an important risk factor for the disease. HC is most commonly seen in the liver and lungs, but retroperitoneal hydatid cyst is very rare. The objective of this study was to evaluate the clinical and radiographic findings and surgical treatment of this unusual lesion.

Increased UGT1A3 and UGT1A7 expression is associated with pancreatic cancer.

UGT1A play important roles in the glucuronidation of a variety of endogenous and exogenous compounds. UGT1A isoforms are expressed tissue specifically. The aim of this study was to examine the relationship between UGT1A3 and UGT1A7 mRNA expression and pancreatic cancer. Paired healthy and tumor tissue samples of 43 patients with pancreatic cancer were included in this study. UGT1A3 and UGT1A7 mRNA expressions were analyzed by real time-PCR. In the result of study, UGT1A3 and UGT1A7 mRNA expressions were significantly higher in tumor tissue than normal tissue of pancreatic cancer patients (p<0.05). In addition, high mRNA expression of UGT1A3 and UGT1A7 was significantly associated with larger tumor size (p<0.05). The data suggested that UGT1A3 and UGT1A7 may play roles in the progression of pancreatic cancer. Consequently, UGT1A3 and UGT1A7 are potential prognostic indicators.

Assessment of the relationship between neutrophil lymphocyte ratio and prognostic factors in non-metastatic colorectal cancer

OBJECTIVE Neutrophil-lymphocyte ratio still has a limited clinical use due to many non-cancer factors affecting neutrophils or lymphocytes in the present time. We aimed to evaluate the association between preoperative neutrophil-lymphocyte ratio and poor prognostic factors after curative elective colorectal surgery. MATERIAL AND METHODS This clinical retrospective study was initiated with 95 patients, who had a curative surgical resection between 2003 and 2013. The patients were divided into two groups based on the preoperative neutrophil-lymphocyte ratio cut-off value above and below 3. The groups were compared for tumor localization, diameter, and staging; the histopathological perineural invasion; lymphovascular invasion; and overall survival. Univariate and multivariate Cox regression analyses were used to determine the role of neutrophil-lymphocyte ratio after stratification by several clinicopathological factors. RESULTS The mean age of patients was 59.79±1.48 (range, 23-90) years, and median follow-up period was 20.77±14.85 months. There was no significant difference in perineural or lymphovascular invasion, tumor size, stage, age, sex, and tumor location between the groups [Group 1 ratio >3 (n=52) and Group 2 ratio ≤3(n=43)]. Hemoglobin (p=0.035) and albumin levels (p=0.004) were lower in the Group 1. When the stage increased, differences between the rectal cancer groups were found. Overall survival was significantly lower in the Group 1 (p=0.013). CONCLUSIONS The study showed that a high neutrophil-lymphocyte ratio had an adverse effect on overall survival in colorectal cancer patients who had a curative surgery. However, we could not establish any association between neutrophil-lymphocyte ratio and the factors such lymphovascular invasion, perineural invasion, tumor size expect hemoglobin and serum albumin levels.

Investigation of MACC1-AS1 gene mutations in colorectal cancer

Colorectal cancer is the frequent cause of mortality in Western world. Metastasis associated with colon cancer 1 (MACC1) gene acts as a key regulator of HGF/Met pathway and is expressed highly in colorectal cancer. MACC1 serves as a prognostic indicator for invasion and metastasis of several cancers. Potential links between MACC1 AS1 RNA locus that located in the intron 6 of MACC1 gene and high expression of MACC1 are unknown. Herein, the secondary structure of MACC-AS1 noncoding RNA and the complementarities between MACC1 mRNA and MACC1-AS1 were analyzed by RNAFold and IntaRNA programs. Since MACC1-AS1 has a proper secondary structure to hybridize with MACC1 mRNA, a potential role of MACC1-AS1 in regulation of MACC1 expression could be thought. The study included 104 controls and 96 patients. Genomic DNA was isolated from blood samples and analyzed by PCR-SSCP and sequence analysis. Three fragments and six genotypes (1, 2, 3, 1&2, 1&3, 2&3) were observed in the exon 1 of MACC1-AS1. A and GT (rs200028381) insertions in genotype 1, G>A substitution and A insertion in genotype 2 were detected. However, no association was observed between these SNPs and colorectal cancer (P>0.05). This is the first investigation on MACC1-AS1 gene mutation in colorectal cancer using molecular techniques. Novel SNPs in exon 1 were identified. In order to understand the association between colorectal tumors and MACC1-AS1 RNA expression clearly; further analysis, like Western blotting and immunohistochemistry of MACC1 and RNA analysis for MACC1-AS1, are needed.

Multifocal Insulinoma in Pancreas and Effect of Intraoperative Ultrasonography.

Insulinoma is the most frequently seen functional pancreatic neuroendocrine tumor. The incidence of multifocal insulinoma is lower than 10%. Its treatment is direct or laparoscopic excision. The present case was examined with the findings of hypoglycemia and hypercalcemia, and as there was high insulin and C-peptide levels the initial diagnosis was insulinoma. The case was investigated in terms of MEN 1. During preoperative screening for localization, there was one focus in the head of the pancreas in the abdominal tomography and two foci in endoscopic ultrasonography. No other focus was detected through intraoperative visual or manual palpation. However, five foci were detected during operation by intraoperative ultrasonography. The relation of masses with the main pancreatic canal was evaluated and they were excised by enucleation method. There was no recurrence during the postoperative 18-month follow-up of the patient. As a result, during treatment for insulinoma, it should be kept in mind that there might be multifocal foci. In all insulinomas, the whole pancreas should be evaluated with intraoperative ultrasonography because none of the current preoperative diagnostic methods are as sensitive as manual palpation of pancreas and intraoperative ultrasonography. The intraoperative detection of synchronous five foci in pancreas is quite a rare condition.