Emin Gökhan Kandemir

MicroRNA-21 as an Indicator of Aggressive Phenotype in Breast Cancer

Objective: The recently discovered microRNAs (miRNAs) are non-protein-coding, endogenous small RNAs. The aim of this study was to investigate the relationship between microRNA-21 (miR-21) and the clinicopathological features of breast cancer. Materials and Methods: Formalin-fixed, paraffin-embedded (FFPE) tissue samples were collected from 15 patients who had undergone surgery for primary breast cancer. The miR-21 expression levels in normal and cancer tissues were analyzed using real-time quantitative reverse transcriptase polymerase chain reaction (real-time qRT-PCR). The correlations between the miR-21 expression level and the stage of disease, the tumor size, lymph node involvement, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, and disease-free survival (DFS) were investigated. Results: The miR-21 expression levels were significantly higher in patients with stage III disease, patients with more than 3 axillary lymph node metastases and HER2-positive patients than in patients with stage I-II disease, patients with 1-3 axillary lymph node metastases and HER2-negative patients (p = 0.005, p = 0.037, and p = 0.014, respectively). Patients with high miR-21 expression level had a significantly shorter DFS than patients with low miR-21 expression level (median DFS: 18 and 56 months, respectively; p = 0.004). Conclusion: These results show that miR-21 is an indicator of an aggressive breast cancer phenotype and that it may be a new therapeutic target in the treatment of breast cancer in the future.

Immunoregulatory Function of HLA-G in Gastric Cancer

BACKGROUND Human leukocyte antigen (HLA)-G-positive gastric cancers are associated with poor survival, but links with tumor escape mechanisms remain to be determined. MATERIALS AND METHODS We used immunohistochemistry to investigate HLA-G expression, tumor infiltrating CD8+ T lymphocytes, and Treg cells in 52 gastric cancer patients. RESULTS There were 29 cancer-related deaths during the follow-up period. Kaplan-Meier analysis indicated that patients with HLA-G-positive (n=16) primary tumors had a significantly poorer prognosis than patients with HLA-G-negative tumors (n=36, p=0.008). The median survival time was 14 months and 47 months, respectively. Patients with high numbers of Tregs and low numbers of CD8+T lymphocytes in the primary tumor had a poorer prognosis than those with low numbers of Tregs and high numbers of CD8+T lymphocytes (p=0.034, p=0.043). Multivariate Cox proportional hazard regression analysis showed that HLA-G expression (hazard ratio: 2.662; 95% confidence interval: 1.242-5.723; p=0.012) and stage (hazard ratio: 2.012;95% confidence interval: 1.112-3.715; p=0.041) were independent unfavorable factors for patient survival. CONCLUSIONS We found a significant positive correlation between HLA-G expression and the number of tumor infiltrating Tregs (p=0.01) and a negative correlation with the number of CD8+T lymphocytes (p=0.041). HLA-G may protect gastric cancer cells from cytolysis by inducing Foxp3+Treg lymphocytes and suppressing CD8+T lymphocytes.

Nesfatin-1 in advanced lung cancer patients with weight loss.

The cachexia occurs frequently in lung cancer patients. Among appetite regulatory peptides, alteration of expressions of leptin and ghrelin is demonstrated in cachectic cancer patients, but nesfatin-1 has not been yet studied in cancer. We investigated serum nesfatin-1 level in advanced lung cancer patients. Forty-one lung cancer patients and 24 healthy subjects were included to the study. Nesfatin-1 serum levels were analyzed by ELISA kit. Serum nesfatin-1 levels were lower in lung cancer patients than in healthy subjects (0.52±0.19ng/ml vs 0.75±0.23ng/ml; p<0.001). In lung cancer patients with weight loss, nesfatin-1 levels were decreased compared to the patients without weight loss (0.44±0.16ng/ml vs 0.63±0.18ng/ml; p<0.001). Whereas, there were no any difference between patients without weight loss and control subjects (0.63±0.18ng/ml vs 0.75±0.23ng/ml; p:0.129) or between SCLC and NSCLC patients (0.53±0.18ng/ml vs 0.52±0.20ng/ml; p:0.458). No significant correlation was found between serum nesfatin-1 values and BMI. In conclusion, loss of fat mass may decrease serum nesfatin-1 level in lung cancer patients with weight loss. The future studies which explore biological significance of low serum nesfatin-1 level in cancer are needed.

Hemicentral Retinal Artery Occlusion in a Breast Cancer Patient Using Anastrozole

Background: Anastrozole, an aromatase inhibitor, is commonly used in the adjuvant treatment of breast cancer. Anastrozole treatment is associated with a risk of thromboembolic events and retinal vascular side effects. Herein, we present a case of hemicentral retinal artery occlusion diagnosed in a breast cancer patient using anastrozole. Case Report: A 53-year-old woman with a hypertensive and diabetic background was admitted to our hospital with breast cancer. Anastrozole treatment was started after surgery, adjuvant chemotherapy, and radiotherapy. Sudden painless loss of vision in the patient’s right eye occurred within 13 months of Anastrozole treatment. A fluorescein angiogram revealed hemicentral retinal artery occlusion. Conclusion: To the best knowledge of the authors, this is the first report of hemicentral retinal artery occlusion in an anastrozole user.

Hyperammonemic encephalopathy in a patient with primary hepatic neuroendocrine carcinoma

A 53-year-old male patient was admitted to our hospital with abdominal pain in the right upper quadrant. There was no change in laboratory investigations other than a slight increase in serum levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and gamma glutamyl transferase (GGT). Computed tomography (CT) of the abdomen showed multiple hepatic nodular lesions in the liver. Tru-cut biopsy of the lesions was reported as well-differentiated neuroendocrine carcinoma. The patient received sandostatin treatment. After a few days, the patient was hospitalized in the intensive care unit with disturbance of consciousness and clinical features suggestive of encephalopathy. Serum ammonia level was found highly elevated. After the treatment with l-ornithine-l-aspartate, a remarkable improvement in the level of patient’s sensorium occurred as well as a reduction in serum ammonia level within a few days. Transarterial chemoembolization (TACE) was performed one week later. The patient’s condition began to worsen along with increase in serum ammonia level and he died because of hyperammonemic encephalopathy. There are case reports of hyperammonemia with some malignancies such as multiple myeloma, plasma cell leukemia, and leiomyosarcoma, or in some patients who have received chemotherapy. This case may suggest an association between hyperammonemia and neuroendocrine tumors.

Platelet indices in patients with colorectal cancer

The interaction between cancer cells and platelets has been known for a long time. Although platelet indices have been also investigated in several clinical settings, it has not been exactly demonstrated in cancer patients. We investigated platelet indices in colorectal cancer patients and compared with healthy subjects. Two hundred and twenty-one colorectal cancer patients and 110 healthy subjects were enrolled into the retrospective study. Data were obtained from computerized medical records of our hospital. Medical record review was performed for all patients regarding thrombocyte indices. Platelet count (325.000/mm3 ± 265.000/mm3 vs 267.000/mm3 ± 67.000/mm3; p=0.025; respectively) and plateletcrit (Pct) (0.25% ± 0.10 vs 0.21 ± 0.05; p<0.001; respectively) were increased in patients compared with healthy subjects while mean platelet volume (MPV) and platelet distribution width (PDW) were similar. The platelet indices were not related to existence of metastasis or acute abdomen. Platelet count and Pct, but not MPV and PDW, are elevated in colorectal cancer patients. Future studies that investigate platelet morphology, function, and putative role of platelets in tumorigenesis and metatasis should be established.

Peripheral blood CD4+CRTH2+ cells in advanced stage non small cell lung cancer

To investigate CD4+CRTH2+ cells in peripheral blood in advanced stage non small cell lung cancer (NSCLC) patients. Forty-six patients with advanced stage NSCLC, who are chemotherapy or radiotherapy naïve, and 17 healthy volunteers, were enrolled in this study. The study was performed using flow cytometry and a complete blood cell counter analyser. CD4+ T cell percentage, CD4/CD8 ratio, CRTH2+CD4+ cell percentages, counts, and mean fluorescein intensity (MFI) and hematological parameters were evaluated in both groups. A survival analysis was performed to compare the patients with high CD4+CRTH2+ cell percentage and those with low CD4+CRTH2+ percentage. CD4+ T cell percentage in total lymphocytes and the CD4/CD8 ratio were lower in the patient group than in the control group. The absolute CD8 T cell count was higher in the patient group than in the control group, whereas the total T cells was not different. The CRTH2+ cell percentage in CD4+ T cells (7.96% ± 6.21% vs 3.37% ± 3.55%; respectively; p: 0,001) and the absolute count of CRTH2+CD4+ cells ( 97 mm-3 ± 109 mm-3 vs 37 mm-3 ± 38 mm-3, respectively; p: 0,033) in the patient group were higher than in the control group, but CRTH2-PE MFI values were not different between groups. Cox regression analysis did not show that CRTH2+CD4+ cell count or percentage is an independent prognostic factor. The study found that CRTH2 expression of CD4+ T cells and CRTH2+CD4+ cell number are higher in the peripheral blood of NSCLC patients than in that of healthy subjects. Further studies that explore the biological significance of high CD4+CRTH2+ cells in lung cancer patients, should be pursued.

Das nicht-kleinzellige Lungenkarzinom – Status Quo 2012

aOnkologischer Schwerpunkt, LungenClinic Groshansdorf, bRangauklinik Ansbach GmbH, Ansbach, cThoraxklinik, Abteilung Innere Medizin – Pneumo logie, Universitatsklinikum Heidelberg, dSektion Pneumologie Innenstadt und Thorakale Onkologie, Klinikum der Universitat Munchen, Lungentumorzentrum Munchen, eUniversitatsmedizin Mannheim, Chirurgische Klinik Interdisziplinare Thorakale Onkologie, Mannheim, fZentrum fur Palliativmedizin, Uniklinik Koln, gPathologisches Institut, Sektion Thoraxpathologie, Universitatsklinikum Heidelberg, hKrankenhaus Martha-Maria, Halle-Dolau, iKlinik fur Strahlen therapie und Radioonkologie, Universitatsklinikum Mannheim, Universitat Heidelberg, Mannheim