Evaluation of Micro-RNA Levels, Apoptosis and Oxidative Stress Markers in Patients Recieving Chemotherapy.

OBJECTIVE: The primary objective of this study was to compare oxidative DNA damage markers, apoptosis markers and changes in miRNA levels in patients diagnosed with cancer and treated through chemotherapy. Our secondary objective was also to evaluate tumor responses that can be determined after post-chemotherapy clinical evaluations by physical examinations, laboratory results and radiological imagings, and to compare the clinical results to oxidative stress and apoptosis markers and micro RNA levels. MATERIALS AND METHODS: To do that we designed a prospective observational cross-sectional study. A total of 34 cancer patients and 27 healthy controls were included in the study from the Harran University School of Medicine Department of Oncology. Newly diagnosed chemotherapy or radiotherapy naive patients without any chronic diseases were included into the study. Patients with a poor performance status (ECOG 2 and 3) and patients who did not meet the inclusion criteria were excluded. The cancer patients received chemotherapy according to their scheduled periods. Blood samples were taken from the patients before the first chemotherapy course and before the second chemotherapy round. Patients were called for toxicity control on the 10th day after the chemotherapy. Pre-chemotherapy, post-chemotherapy and control group miR-29a expression levels, change in apoptosis markers and oxidative DNA damage markers were obtained and compared. We studied 8-hydroxy 2-deoxyguanosine, total oxidant status, total anti-oxidant status, and oxidative status index for oxidative stress markers. We studied M30 and M65 as apoptosis markers. Clinical results of efficiency of the chemotherapy was acquired and compared to biochemical markers based on chemotherapy results. Chemotherapy toxicities were recorded. RESULTS: As a result, we found oxidative DNA damage markers and apoptosis markers were high in the cancer group, demonstrating that oxidative DNA damage and apoptosis might play a direct or indirect role in cancer etiology. However, there were subtle differences between pre-chemotherapy and post-chemotherapy levels. Mir-29a expressions were lower in cancer patients as compared to controls. However, the expression levels were not significantly change in pre- and postchemotherapy status. Moreover, we found no relationship between clinical status of patients (progression and regression) and studied biochemical markers. CONCLUSION: Thus, checking for DNA damage markers and taking precautions to lower the levels of these markers in individuals with cancer risk may be helpful in preventing cancer.

Polymorphisms in the MTHFR gene are associated with recurrence risk in lymph node-positive breast cancer patients.

PURPOSE: The aim of this study is to clarify the relationship between recurrence risk of breast cancer and methylenetetrahydrofolate reductase (MTHFR) C677T polymorphisms. PATIENTS AND METHODS: Breast cancer patients who had undergone surgery in Gaziantep University Oncology Hospital between June 2005 and June 2012 were followed-up and retrospectively enrolled in this study. Blood samples were collected from all patients to assess MTHFR C677T polymorphisms. Stage according to tumor-node-metastasis system, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 status, grade of disease, menopausal status, and administered chemotherapy or hormonal therapy were recorded. Effects of these parameters on recurrence risk were evaluated using univariate analysis and multivariate binary logistic regression model. RESULTS: Association of MTHFR C677T polymorphisms with recurrence risk was evaluated in 298 patients whose median age was 47 years (range: 21-79 years). In all patients, age (odds ratio [OR] =0.953, P=0.005) and N3 lymph node status (OR =6.293, P=0.001) were found to affect the recurrence risk. While MTHFR homozygote genotype did not have an effect on recurrence risk in all patients, increased risk was observed in lymph node-positive subgroup (OR =4.271; 95% CI 1.515-12.023; P=0.006). Adjusting for age, tumor size (T), and node status (N), MTHFR homozygote genotype had more statistically significant risk for recurrence (OR =3.255; 95% CI 1.047-10.125; P=0.041). CONCLUSION: MTHFR TT genotype was found to be associated with increased recurrence risk in patients with lymph node-positive breast cancer.

Correlation of educational status and clinicopathological characteristics of breast cancer: a single center experience.

PURPOSE: Educational status may be an important parameter in assessing breast cancer risk and prognosis. The purpose of this study was to investigate the correlation between the level of education and clinicopathological characteristics of breast cancer, including tumor grade, HER-2 and estrogen receptor (ER) status, tumor size, axillary lymph node involvement and metastasis. METHODS: The study included 1800 women who were diagnosed with invasive breast cancer during 2005-2013 at Hacettepe University Cancer Institute. Patients were divided into three groups according to their educational status at the time of diagnosis as follows: low (illiterate and elementary school, 5 years or less of education), medium (secondary school and upper secondary school, 6-12 years of education) and high (university level, more than 12 years of education). The associations between educational status and clinicopathologic features of breast cancer at the time of diagnosis were evaluated. RESULTS: In all patient, a significant relationship was found between educational status and T stages (p<0.0001). Patients with higher educational levels were reported to have smaller tumor size regardless to their age and were less likely to have axillary lymph node involvement (p=0.001) or metastasis (p=0.001). A significant correlation was found between educational status and ER positivity in patients over 50 years of age (p=0.03). When the patients of all ages were evaluated, no statistically significant correlation was shown (p=0.27) between educational status and ER positivity. A significant relationship was found between educational status and HER-2 status (p=0.003), regardless of the patients' age. HER-2 positivity increased in patients with low educational status, however this significance was lost in patients over the age of 50 (p=0.1). CONCLUSION: The relationship between educational status and biological factors in breast cancer are not conclusive as yet, but this particular study revealed that educational status played a major influence in each of the five breast cancer prognostic factors: ER status, HER-2 status, tumor size, lymph node status and metastasis.

Evaluating the safety of intracameral bevacizumab application using oxidative stress and apoptotic parameters in corneal tissue.

AIM: To investigate the possible effects of intracameral bevacizumab on oxidative stress parameters and apoptosis in corneal tissue. METHODS: In total, 30 rats were assigned randomly into the following three groups of 10 rats each: a sham group (Group 1; n=10), a control group [Group 2; balanced salt solution (BSS) was administered at 0.01 mL; n=10], and a treatment group (Group 3; bevacizumab was administered at 0.25 mg/0.01 mL; n=10). The total antioxidant status (TAS) and the total oxidant status (TOS) in the corneal tissue and blood samples were measured, and the oxidative stress index (OSI) was calculated. Additionally, corneal tissue histopathology was evaluated for caspase-3 and -8 staining and apoptotic activity. RESULTS: In the blood samples, the TAS, TOS, and OSI levels were not significantly different (all P>0.05). Compared with the sham and control groups, the TOS and OSI levels in the corneal tissues were significantly different in the bevacizumab group (all P<0.05). No statistically significant differences were observed between the sham and control groups (all P>0.05). However, compared with the sham and control groups, greater immunohistochemical staining for caspases-3 and -8 and an elevated level of apoptotic activity were observed in the bevacizumab group. CONCLUSION: This study revealed that intracameral bevacizumab injections seemed to be systemically safe but may have elicited local toxic effects in the corneal tissue, as indicated by the oxidative stress parameters and histopathological evaluations.

Prior cholecystectomy predisposes to acute pancreatitis in codeine-prescribed patients.

In this paper, we report a case of drug-induced pancreatitis just after taking a pain pill including a low-dose combination of acetaminophen and codeine. Codeine-induced pancreatitis has been rarely reported, however, well-established. The proposed mechanism for codeine-induced pancreatitis is by increasing Oddi sphincter pressure. However, the clinically important point is that the codeine-induced pancreatitis is seen almost only in the cholecystectomized patients due to lacking of its reservoir capacity. Codeine is commonly used alone or in combination in pain medicine. Therefore, it is fairly important to question whether a patient underwent cholecystectomy when a physician decides to prescribe codeine-included preparations.

Efficacy of capecitabine monotherapy as the first-line treatment of metastatic HER2-negative breast cancer.

AIMS AND BACKGROUND: Capecitabine is a potent and safe agent that can be used after anthracycline and taxane treatment in patients with metastatic breast cancer (MBC). The purpose of this study was to investigate the efficacy and safety of capecitabine monotherapy as a first-line treatment in human epidermal receptor 2 (HER2)-negative patients with MBC. METHODS AND STUDY DESIGN: In this single-center trial, a total of 109 HER2-negative patients with MBC who received capecitabine monotherapy as first-line treatment between 2003 and 2014 were retrospectively analyzed. Kaplan-Meier survival analysis was carried out for progression-free survival (PFS) and for overall survival (OS). Two-sided p values of <0.05 were considered statistically significant. RESULTS: Median PFS was 7.0 ± 0.67 (confidence interval (CI) 5.6-8.3) months and median OS was 30 ± 4.1 (CI 21.8- 38.1) months. First-line capecitabine treatment for HER2-negative MBC was more effective in the estrogen receptor (ER)-positive patient population compared to the ER-negative group (median PFS 9 vs 4 months (p = 0.002), median OS 33 vs 21 months (p = 0.01)). Indeed, the overall response rate in the ER-negative group was 16%, while this was calculated as 38% for ER-positive cases. While most of our patient population was treated with a higher dose (1250 mg/m2), the observed grade 3-4 toxicities were lower compared to some previously reported phase II and phase III capecitabine studies. CONCLUSIONS: Capecitabine monotherapy is an effective and safe regimen for ER-positive, HER2-negative patients with MBC. Its low toxicity profile compared to other intravenous cytotoxic agents and the ease of its oral administration make this agent a preferable option for both physicians and patients.

Chemotherapy might not be beneficial in lymph node- negative, hormone-positive, and HER2-negative breast cancer patients: a long-term retrospective analysis.

INTRODUCTION: In lymph node-negative, hormone-positive, and Her2-negative breast cancer patients, the benefits of adding adjuvant chemotherapy to hormonal therapy continue to be debated, especially for low to intermediate grade and small tumors. METHODS: Excluding patients with T4 disease, we retrospectively reviewed the records of patients with long-term follow-up at our center between 2003 and 2014. Among node-negative, hormone-positive and HER2-negative breast cancer patients, we compared two groups of patients: those given both chemotherapy (doxorubicin+cyclophosphamide) and hormonotherapy, and those prescribed hormonotherapy alone. The primary endpoints were progression-free (PFS) and overall survival (OS). RESULTS: Overall, no difference was observed between these two treatment groups in either DFS or OS. However, for both outcomes, there was a trend towards improved DFS and OS favoring the hormone-only group. CONCLUSIONS: In selected subgroups of breast cancer patients, administering adjuvant hormonal therapy alone seems to be at least as good if not better than combining hormonotherapy and chemotherapy.

A retrospective analysis of adjuvant CAF, AC-T and TAC regimens in triple negative early stage breast cancer.

PURPOSE: To compare the effectiveness of adjuvant chemotherapy regimens in triple negative breast cancer (TNBC) for which no protocol has been determined to be treatment of choice. METHODS: In this single-center retrospective trial, we analyzed the adjuvant regimens of 164 TNBC patients among 3253 breast cancer patient records. Adjuvant TAC (docetaxel, doxorubicin, cyclophosphamide), CAF (cyclophosphamide, doxorubicin, 5fluorouracil), and AC-T (doxorubicin, cyclophosphamide followed by docetaxel) regimens were compared in terms of disease free survival (DFS) and overall survival (OS). RESULTS: In terms of both DFS and OS TAC was significantly superior to AC-T in node positive TNBC. When node negative and positive patients were analyzed together, TAC was still significantly superior to AC-T in terms of DFS and OS. There was a trend favoring CAF over AC-T, however, it was only significant in terms of OS when all node negative and positive TNBC patients were incorporated together. CONCLUSION: In the adjuvant setting, especially in node positive patients, TAC should be the treatment of choice in TNBC patients. CAF is probably better than AC-T in TNBC.

The role of the UTS2 gene polymorphisms and plasma Urotensin-II levels in breast cancer.

Breast cancer is the most common malignancy predominantly affecting women. To date, numerous numbers of studies were reported novel genetic contributors with diagnostic, prognostic, and therapeutic potential for the breast carcinogenesis. However, the role of urotensin-II in breast carcinogenesis has not been elucidated yet. Urotensin-II is a somatostatin-like cyclic tiny peptide identified by its potent vasoconstrictor activity. Soon after its discovery, its involvement in many disease states as well as its expression in various tissues including the tumors have been demonstrated. Moreover, there is strong evidence that suggest urotensin-II as the significant contributor of angiogenesis as well as cell proliferation and tumor biology. In this study, enzyme-linked immunosorbent assay (ELISA) and restriction fragment length polymorphism analysis were used to evaluate plasma levels of urotensin-II and Thr21Met and Ser89Asn polymorphisms of UTS2 gene in breast cancer patients. In the present case-control study, we noticed a significant decrease in the levels of urotensin-II protein in the plasma of the breast cancer patients (p < 0.05). Also, Thr21Met polymorphism in the UTS2 gene was associated with the risk of developing breast cancer (p < 0.0001), whereas the genotype frequency of Ser89Asn was found to be similar in patients and controls (p > 0.05). In addition, we demonstrated the gradual decreasing of urotensin-II protein levels from TT and TM to MM genotypes. In conclusion, these results strongly suggest that urotensin-II could contribute to breast carcinogenesis and Thr21Met polymorphism can be an important risk factor in developing breast tumors.

Influence of ethnicity on survival of breast cancer patients in Turkey.

BACKGROUND: Kurdish women with breast cancer have more unfavorable prognostic factors than their Turkish and Arab counterparts. However, the effects of these factors on breast cancer survival among these ethnic groups remain unclear. We therefore investigated the impact of ethnicity on survival in breast cancer patients in Turkey. MATERIALS AND METHODS: Ethnicity, age, stage at diagnosis, tumor characteristics, treatments given (surgery, chemotherapy, radiotherapy and hormone therapy), and survival times were recorded. Kaplan- Meier analysis was used to estimate the overall survival times and survival plots. Log-rank test was used to compare the survival curves. RESULTS: Of the 723 breast cancer patients included in the study, 496 (68.7%) were Turkish, 189 (26.2%) were Kurdish, 37 (5.1%) were Arabic and 1 was Armenian. Kurdish women with breast cancer had larger tumor sizes and higher rates of hormone receptor negative tumors than Turkish and Arab patients. Mean follow-up time was 118.4 [95% Confidence Interval (CI): 95.4-141.3] months, and it was 129.9 (95% CI: 93.7-166.2), 124.2 (95% CI: 108.4-140.1) and 103.1 (95% CI: 85.9-120.4) months for Turkish, Arabic and Kurdish patients, respectively. CONCLUSIONS: Kurdish ethnicity is associated with higher rates of hormone receptor negative and triple-negative tumors and with worse survival. Clinical and epidemiological research is warranted to elucidate reasons underlying overall survival, variations in tumor biology, differences in treatment responsiveness, and effects of social factors among ethnic groups in Turkey.

Evaluation of oxidative stress parameters and urinary deoxypyridinoline levels in geriatric patients with osteoporosis.

[Purpose] To evaluate the oxidative stress parameters and urinary deoxypyridinoline levels in geriatric patients with osteoporosis. [Subjects and Methods] Eighty geriatric patients aged over 65 years were recruited. Patients were divided into two groups: Group 1 (n=40) consisted of patients with osteoporosis, and Group 2 (n=40) consisted of patients without osteoporosis. Bone mineral density measurements were performed for all patients using DEXA. Oxidative stress parameters were analyzed in blood samples, and deoxypyridinoline levels were analyzed in 24-hour urinary samples. [Results] Compared to Group 2, the total antioxidant status and oxidative stress index levels of Group 1 were not significantly different; however, total oxidant status and 24-hour urinary deoxypyridinoline levels were significantly higher. Pearson correlation coefficients indicated that OSI and urinary deoxypyridinoline levels were not correlated with any biochemical parameters. ROC-curve analysis revealed that urinary deoxypyridinoline levels over 30.80 mg/ml predicted osteoporosis with 67% sensitivity and 68% specificity (area under the curve = 0.734; %95 CI: 0.624-0.844). [Conclusion] Our results indicate that oxidative stress would play a role in the pathogenesis of osteoporosis, and that urinary deoxypyridinoline levels may be a useful screening test for osteoporosis.

Importance of HER2 Work-Up and Treatment Even in Patients with Poor Performance Status: A Case Report.

Gastric cancer is one of most common types of cancers. Metastatic gastric cancer has a poor prognosis and is accepted as incurable at this stage. Treatment of metastatic gastric cancer did not progress substantially until new targeted agents have come out. Recently published ToGA trial showed promising results in HER2 overexpressing metastatic gastric cancer. In this case we present a case with an excellent complete response with anti-HER2 treatment. Most importantly, we wanted to emphasize (1) the importance of early determination of HER2 overexpression, and (2) to draw attention of anti-HER2 agents in the first line treatment even in patients with a poor performance status.

Depression, anxiety and quality of life through the use of complementary and alternative medicine among breast cancer patients in Turkey.

BACKGROUND AND AIM: Breast cancer is the most common type of cancer amongst women today. The aim of this study was to examine the association between complementary and alternative medicine (CAM) and the quality of life (QoL), anxiety and depression and demographic characteristics of women with breast cancer. MATERIALS AND METHODS: QoL was measured by the European Organization for Treatment and Research of Cancer quality of life core questionnaire (QLQ-C30, version 3.0) and anxiety and depression was measured by the hospital anxiety and depression scale. RESULTS: In total, 122 patients with breast cancer were enrolled in the study and 50% (n=61) of them reported that they were using CAM. The most commonly used CAM methods were stinging nettle (57%) and prayer and spiritual healing (49%). No relationship was found between the use of CAM and the patient's age, time to diagnosis, cancer stage, chemotherapy use, smoking and residence. However, the analyses showed a positive association between CAM and role functioning (P=0.014) and financial difficulties (P=0.011); and a negative association between CAM and emotional functioning (P=0.033). CONCLUSIONS: Based on the previous studies, 20-83.3% of breast cancer patients among different countries and cultures used CAM. Our results suggested that the use of CAM among women is quite popular, but they showed no correlation between CAM usage and anxiety and depression. In addition, CAM usage was more common in breast cancer patients with a poor emotional and financial status.

Crohnic kidney disease: recurrent acute kidney failure in a patient with Crohn's disease.

CONTEXT: Short bowel syndrome is a rare and devastating complication in chronic inflammatory bowel disease following functional or anatomic loss of extensive segments of the intestine. CASE REPORT: A 60-year-old male patient with Crohn's disease had undergone multiple resections of the intestine and developed short bowel syndrome. Despite up to 4-5 liters of orally fluid, sufficient calcium and magnesium intake, he suffered from recurrent acute kidney injury due to profound volume depletion and those electrolyte deficiencies. Administration of intravenous fluid and electrolyte repleacement treatment at regular intervals prevented further kidney injuries. CONCLUSION: We present a case of recurrent acute kidney failure in a patient with Crohn's disease, and aimed to remark importance of receiving sufficient parenteral fluid and electrolyte support in those with short bowel syndrome.

Urotensin-II and endothelin-I levels after contrast media administration in patients undergoing percutaneous coronary interventions.

BACKGROUND: Contrast induced kidney injury is an acute renal dysfunction that is secondary to the administration of radio contrast media. The purpose of this study was to evaluate the levels of urotensin-II (UT-II) and endothelin-I (ET-I) after contrast media administration in patients undergoing percutaneous coronary interventions. MATERIALS AND METHODS: In this prospective cohort study, we evaluated 78 patients with coronary artery disease who were scheduled for and ultimately underwent percutaneous coronary interventions. As a contrast material, nonionic contrast media was used in various amounts (70-480 mL). Blood and urine samples were obtained to measure U-II, ET-I just before and at the twenty-fourth hour of percutaneous coronary interventions. RESULTS: Compared to baseline, twenty-fourth hour creatinine levels were significantly increased (P < 0.001). The twenty-fourth hour serum and urine levels of both UT-II and ET-I were also significantly increased compared to baseline (P < 0.001 for all) and 24(th) hour serum and urine UT-II (r = 0.322, P = 0.004; r = 0.302, P = 0.007 respectively), ET-I (r = 0.511, P < 0.001; r = 0.266, P = 0.019 respectively) levels were significantly correlated with the amount of contrast media. CONCLUSION: Our study indicates that; increased UT-II and ET-I levels seem to be a consequence of hazardous effects of contrast media on blood vessels and the kidney.

Evaluation of oxidative stress parameters and metabolic activities of nurses working day and night shifts.

The aim of this study was to evaluate the oxidative stress and metabolic activities of nurses working day and night shifts. Intensive care unit (ICU) (n=70) and ordinary service (OS) nurses (n=70) were enrolled in the study. Just before and the end of the shifts, blood samples were obtained to measure the participants' oxidative stress parameters. Metabolic activities were analyzed using the SenseWear Armband. Oxidative stress parameters were increased at the end of the shifts for all OS and ICU nurses compared to the beginning of the shifts. Compared to the OS nurses, the ICU nurses' TAS, TOS, and OSI levels were not significantly different at the end of the day and night shifts. The metabolic activities of the OS and ICU nurses were found to be similar. As a result, the OS and ICU nurses' oxidative stress parameters and metabolic activities were not different, and all of the nurses experienced similar effects from both the day and night shifts.

Evaluation of oxidative stress parameters and metabolic activities of nurses working day and night shifts / Avaliação de parâmetros de estresse oxidativo e as atividades metabólicas das enfermeiras trabalhando em turnos diurnos e noturnos / Evaluación de parámetros de estrés oxidativo y actividades metabólicas de enfermeras trabajando en turnos diurnos y nocturnos

O objetivo deste estudo foi avaliar o estresse oxidativo e as atividades metabólicas das enfermeiras em turnos diurnos e noturnos. Enfermeiras da Unidade de Tratamento Intensivo (UTI) (n=70) e do serviço comum (SC) (n=70) participaram do estudo. Logo no início e ao final dos turnos, amostras de sangue foram obtidas para medir parâmetros de estresse oxidativo. Atividades metabólicas também foram analisadas com o uso da braçadeira SenseWear. Parâmetros de estresse oxidativo aumentaram no fim dos turnos de todas as enfermeiras SC e UTI quando comparados ao início dos turnos. Comparados às enfermeiras SC, os níveis de TAS, TOS e OSI das enfermeiras de UTI não eram significativamente diferentes no final dos turnos diurnos e noturnos. Além disso, as atividades metabólicas das enfermeiras de SC e UTI se revelaram como sendo similares. Assim, os parâmetros de estresse oxidativo e as atividades metabólicas das enfermeiras SC e UTI não eram diferentes, e todas as enfermeiras sofrem efeitos semelhantes dos turnos, tanto no dia quanto na noite.

The aim of this study was to evaluate the oxidative stress and metabolic activities of nurses working day and night shifts. Intensive care unit (ICU) (n=70) and ordinary service (OS) nurses (n=70) were enrolled in the study. Just before and the end of the shifts, blood samples were obtained to measure the participants' oxidative stress parameters. Metabolic activities were analyzed using the SenseWear Armband. Oxidative stress parameters were increased at the end of the shifts for all OS and ICU nurses compared to the beginning of the shifts. Compared to the OS nurses, the ICU nurses' TAS, TOS, and OSI levels were not significantly different at the end of the day and night shifts. The metabolic activities of the OS and ICU nurses were found to be similar. As a result, the OS and ICU nurses' oxidative stress parameters and metabolic activities were not different, and all of the nurses experienced similar effects from both the day and night shifts.

Se objetivó evaluar estrés oxidativo y actividades metabólicas de enfermeras en turnos diurnos y nocturnos. Participaron enfermeras de Unidad de Terapia Intensiva (UTI, n=70) y del servicio común (SC, n=70). Se obtuvieron muestras sanguíneas al inicio y al final de los turnos para medir parámetros de estrés oxidativo. Las actividades metabólicas también fueron analizadas utilizando brazaletes SenseWear. Los parámetros de estrés oxidativo aumentaron hacia el final de los turnos de todas las enfermeras SC y UTI, comparados con la medida de inicio. Los niveles de TAS, TOS y OSI no eran significativamente diferentes entre enfermeras SC y UTI al cierre de los turnos diurnos y nocturnos. Las actividades metabólicas de enfermeras SC y UTI se mostraron similares. Consecuentemente, los parámetros de estrés oxidativo y las actividades metabólicas de enfermeras SC y UTI no resultaron diferentes, y todas las enfermeras sufren efectos semejantes en sus turnos, tanto diurnos como nocturnos.