In vitro investigation of the effect of matrix molecules on the behavior of colon cancer cells under the effect of geldanamycin derivative.

The chaperone-binding drug, 17-allylamino-17-demethoxygeldanamycin, has recently come into clinical use. It is a derivative of geldanamycin, an ansamycin benzoquinone antibiotic with anti-carcinogenic effect. Understanding the effect of this drug on the cancer cells and their niche is important for treatment. We applied 17-allylamino-17-demethoxygeldanamycin to colon cancer cell line (Colo 205) on matrix molecules to investigate the relationship of apoptosis with terminal deoxynucleotidyl transferase dUTP nick end labeling immunocytochemistry and related gene expression. We used laminin and collagen I for matrix molecules and vascular endothelial growth factor for angiogenic structure. We also examined apoptosis-related signaling pathway including mitochondrial proteins, cytochrome c, Bcl-2, caspase-9, Apaf-1 expression using real-time polymerase chain reaction. There was clear effect of 17-allylamino-17-demethoxygeldanamycin that killed more cells on tissue culture plastic compared to matrix molecules. The IC50 value was 0.58 µg/mL for tissue culture plastic compared with 0.64 µg/mL for laminin and 0.75 µg/mL for collagen I. The analyses showed that more cells on matrix molecules underwent apoptosis compared to that on tissue culture plastic. Apoptosis-related gene expression was similar in which Bcl-2 expression decreased and proapoptotic gene expression of the cells on matrix molecules increased compared to that on tissue culture plastic. However, the application of 17-allylamino-17-demethoxygeldanamycin was more effective for the cells on collagen I compared to the cells on laminin. There was also a decrease in angiogenesis as shown by the vascular endothelial growth factor staining. This was more pronounced by coating of the tissue culture plastic with matrix molecules. Our results supported the anti-cancer effect of 17-allylamino-17-demethoxygeldanamycin, and this effect depended on matrix molecules. This effect occurs through apoptosis, and related genes were also altered. All these genes may serve for novel target under the effect of matrix substrate. However, correct interpretation of the results requires further studies.

Possible relations between oxidative damage and apoptosis in benign prostate hyperplasia and prostate cancer patients.

Cancer has been described as the twentieth century plague, and is a very common health problem. It has been reported that ROS and ROS products play a key role in cancer and that oxidative damage is effective in apoptosis initiation. In this study we aimed to evaluate the relationship between MDA (malondialdehyde), DNA damage (8-hydroxyguanine, 8-OH-dG), and caspase-3 in BHP and prostate cancer patients. Twenty male patients with prostate cancer and 20 male patients with benign prostate hyperplasia were included into this study. The MDA (nanomole), DNA damage (nanograms per millilitre), and caspase-3 (nanograms per millilitre) levels were measured in prostate cancer and benign prostate hyperplasia using Elisa kits (Millipore Corporation, Billerica, MA, USA). In the prostate cancer group, serum MDA (30.96 ± 9.25) and DNA damage (4.42 ± 0.36) levels were significantly raised (p < 0.05) when compared to the benign prostate hyperplasia group (24.05 ± 8.06, 3.99 ± 0.54). However, in the prostate cancer group, serum caspase-3 (2.36 ± 0.82) levels were statistically significantly lowered (p < 0.05) compared with the benign prostate hyperplasia group (3.15 ± 1.04). We observed that altered prooxidant, DNA damage levels may lead to an increase in oxidative damage and may consequently play an important role in prostate carcinogenesis. These findings indicate that, although the triggering of these changes is unknown, changes in the levels of MDA, DNA damage, and caspase-3 in the blood are related to prostatic carcinoma development. In addition, it would be appropriate to conduct new studies with a large number of patients at different stages.

Capsaicin inhibits cell proliferation by cytochrome c release in gastric cancer cells.

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the principal pungent component in hot peppers. The role of capsaicin in carcinogenesis is quite controversial. Although some investigators suspect that capsaicin is a carcinogen, co-carcinogen, or tumor promoter, others have reported that it has chemopreventive and chemotherapeutic effects. The present study aimed to evaluate the cytotoxicity and chemosensitizing activities of capsaicin alone and on 5-flourouracil (5-FU)-treated gastric cancer cells. In this study, the gastric cancer cell line HGC-27 was used and capsaicin used as a chemosensitizer and 5-flourouracil (5-FU) was used as chemotherapeutic. Cytotoxicity and chemosensitizing activities were analyzed with MTT assay; supernatant levels of LDH and glucose were detected as biochemical markers of cell viability; cytochrome c and AIF were evaluated with western blot; and additionally, wound-healing assays were employed. Results suggested that capsaicin had significant anticancer abilities; such capsaicin were capable of causing multifold decreases in the half maximal inhibitory concentration IC50 value of 5-FU. The continuing controversy surrounding consumption or topical application of capsaicin clearly suggests that more well-controlled epidemiologic studies are needed to evaluate the safety and efficacy of capsaicin use. In summary, the present study demonstrated that capsaicin has the potential to be used for treating gastric carcinoma with 5-FU in vitro.

Delivery in a vertical birth chair supported by freedom of movement during labor: A randomized control trial.

To evaluate the effect of delivery in a vertical birth chair (VBC) and traditional delivery table (DT) supported by women's movement during labor on the labor process, fetal outcome, maternal hormone levels, birth comfort, and satisfaction. This randomized controlled trial was conducted with 1:1:1 allocation. Group 1: in the VBC in upright position, Group 2: on the DT in supine position, these groups supported by freedom of movement, control group: on the DT in supine position, labor in bed. The duration of second stage of labor was not different between the groups (p = 0.246). The occurrence of instrumental birth, episiotomy, and perineal laceration was also not different among the groups (p = 0.772, p = 0.953, and p = 0.124). The use of uterotonic was observed in control group (p = 0.001). 1 and 5 APGAR scores of newborns were not different in all groups (p = 0.121, p = 0.268). The lowest pain score was observed in Group 1 (p = 0.001). Birth comfort and satisfaction were higher in Group 1 (p = 0.001 and p = 0.001). Decreased postpartum prolactin levels and increased postpartum oxytocin levels were observed in the control and Group 1 (p = 0.004, p = 0.006). Freedom of movement during labor and delivery using VBC in upright position can play birth-promoting and supporting role. There were no negative effects on the fetal outcome.

The effect of COVID-19 vaccinations on menstrual cycle and serum anti-Mullerian hormone levels in reproductive age women.

The aim of this prospective cohort study was to investigate the effect of coronavirus disease 2019 (COVID-19) vaccinations on menstrual cycle and ovarian reserve in reproductive aged-women. Health care providers (n = 258) vaccinated with inactivated (CoronaVac) and mRNA based (Pfizer-BioNTech®) COVID-19 vaccines were included. All subjects completed a gynaecological and menstrual history questionnaire and Anti-Mullerian Hormone (AMH) levels were measured in serum samples collected before first vaccination and at 1st, 3rd, 6th and 9th months. The prevalence of new-onset menstrual dysregulation following vaccination was 20.6% and it was statistically significant compared to baseline (p = 0.001). Menstrual pattern turned back to normal in 59.6% of vaccinated women. Serum AMH levels gradually decreased until 6th month of follow-up compared to baseline (p < 0.001). A significant increase in serum AMH level was observed at 9th month of follow-up compared to 6th month follow-up levels (p < 0.001). The decrease in serum AMH level was statistically significant regardless of serum anti SARS-CoV-2 antibody levels, subgroups of age, occupation, menstrual dysregulation following vaccination and presence of gynaecological diseases. In conclusion, vaccination against SARS-CoV-2 causes a transient decrease on serum AMH levels and moderate irregularities in menstrual pattern increasing with age and is mostly reversible.

Prospective evaluation of free radicals and antioxidant activity following 6-month risedronate treatment in patients with postmenopausal osteoporosis.

In addition to the well-described implications of estrogen deficiency in postmenopausal osteoporosis (PMO), free radicals are also effective on bone metabolism. The antioxidant vitamins C and E play an important role in the production of collagen, mesenchymal cell differentiation into osteoblasts, and bone mineralization. Therefore, the incidence of osteoporosis and the risk of fractures were decreased with vitamin C and E. It was proposed that free oxygen radicals are responsible for biological aging, atherosclerosis, carcinogenesis, and osteoclastic activity via their negative effects on the cell and DNA. In this study, we aimed to investigate and compare the levels of free radicals and serum antioxidant activity in patients with PMO and healthy subjects before and after six-month treatment with risedronate, which is an inhibitor of bone resorption. Twenty-three postmenopausal patients aged between 52-83 (mean [± standard deviation] 67.6 ± 8.17) with T scores below -2.5 in femur neck or L1-L4, and 23 postmenopausal healthy subjects were enrolled into the study. Patients who had received any medications within the last 6 months that could alter bone metabolism were excluded. Serum malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) levels were analyzed in both groups. The patients with PMO were commenced on 5 mg of risedronate, 1,200 mg of calcium, and 800 IU of vitamin D daily. The patients were reevaluated at the end of the sixth month. MDA and SOD levels were similar in patients with PMO when compared to the healthy group before the treatment, while the GPx levels were lower in patients with PMO (P = 0.014). GPx (P = 0.028) and MDA (P = 0.04) levels were increased in patients with PMO after the treatment. In contrast, SOD levels were decreased when compared to the initial levels (P = 0.006). There may be an insufficiency in different steps of the enzymatic antioxidant systems in patients with PMO without treatment. We observed an increment in lipid peroxidation levels and GPx levels with risedronate. We think that the decrement in SOD levels may be related with the utilized antioxidants due to the increased free radicals and the compensatory increment in the other steps of the antioxidant system.

The effect of postpartum period back massage on serum ghrelin, leptin, adiponectin and visfatin levels.

In addition to the initiation and continuity of lactation, hormones transferred from mother plasma to milk during breastfeeding are also important. The aim of this study was to determine the effect of back massage on maternal serum ghrelin, leptin, adiponectin and visfatin levels in women giving birth. A total of 60 mothers, participated in this experimental study. Massage was applied in the first 3-4 h after birth. Blood sample was taken in the postnatal routine. It was determined that the intervention group did not make a statistically significant difference in ghrelin (1.37 ± 0.7, 1.00 ± 0.2), leptin (0.76 ± 0.5, 0.70 ± 0.1), adiponectin (3.55 ± 0.8, 3.05 ± 0.5) levels compared to the control group (p > 0.05). However, visfatin (10.53 ± 2.4, 9.97 ± 2.0) levels were statistically higher than the control group (p < 0.05). Back massage was found to be beneficial in terms of increased growth factors in breast milk production and content.

Effect of Multiple Sclerosis on Dyadic Adjustment.

PURPOSE: This study examines the dyadic adjustment of married men and women with multiple sclerosis (MS). METHOD: This cross-sectional study consists of 40 patients with MS who were married and being followed in the neurology clinic of a university hospital. Data collection was performed by face-to-face interviews with only the participant and the researcher present. The participants filled in the Expanded Disability Status Scale, a sociodemographic form, and a dyadic adjustment scale. RESULTS: The study group was 75% male, with age ranging from 27 to 65 years (mean, 44.40 ± 9.31 years). Expanded Disability Status Scale scores ranged from 0 to 7 (mean, 3.25 ± 1.94); 95% of the subjects were having relapses and remissions. Scores for patients with MS who were not considering divorce were statistically significantly higher than patients with MS who were considering divorce for dyadic adjustment (z = 3.845, P = .000), common view (z = 2.336, P = .020), endearment (z = 2.701, P = .007), and total scores (z = 3.399, P = .001). CONCLUSION: Most of the patients with MS who participated in this study were diagnosed with relapsing-remitting MS with a mean Expanded Disability Status Scale score of 3, indicating that patients had the physical ability to perform routine activities. The total dyadic adjustment scale score (107.7) is above average, indicating that dyadic adjustment was at a good level.

Effect of oncological treatment on serum adipocytokine levels in patients with stage II-III breast cancer.

Adipose tissue-derived hormones (adipocytokines), such as adiponectin, leptin, resistin and visfatin, and the pancreatic hormone insulin, have been suggested to play a role in carcinogenesis. we therefore hypothesized that the oncological treatment of breast cancer may alter the serum levels of these adipocytokines and insulin. In this study, we aimed to compare the serum levels of adipocytokines and insulin between the pre- and post-treatment period in patients with breast cancer. In this prospective study, 20 consecutive patients with stage II and III breast cancer underwent breast-conserving surgery or total mastectomy and/or axillary dissection. The patients received adjuvant chemotherapy and radiotherapy, if necessary. Blood samples were obtained during the preoperative period and postoperatively after completion of the adjuvant therapy. There was no statistically significant difference between the pre- and post-treatment levels of visfatin, adiponectin and leptin. However, the serum insulin and resistin levels and insulin resistance were found to be statistically significantly increased following treatment (P<0.05). Post-treatment resistin levels were positively correlated with insulin resistance (r=0.45, P<0.05). Therefore, oncological treatment of stage II and III breast cancer did not affect visfatin, adiponectin and leptin levels, but statistically significantly increased resistin levels and insulin resistance. In addition, the post-treatment resistin levels were positively correlated with insulin resistance, suggesting that resistin may be involved in the development of insulin resistance in breast cancer patients following treatment.

Evaluation of proinflammatory cytokine and neopterin levels in women with papillary thyroid carcinoma.

INTRODUCTION: Papillary thyroid cancer is a disease that has been associated with chronic inflammation. The purpose of this study is to measure the production of the proinflammatory cytokines IL-1ß, IL-6 and IL-8 and neopterin, which is a novel biomarker for cellular immune response in papillary thyroid cancer. MATERIALS AND METHODS: The serum IL-1ß, IL-6, IL-8 and neopterin values of 31 papillary thyroid cancer patients undergoing bilateral total thyroidectomy were measured before and 20 days after surgery. The values were compared with those of 39 healthy controls. RESULTS: Serum IL-1ß levels were similar across groups. IL-6 (p<0.001), IL-8 (p = 0.015) and neopterin levels (p = 0.002) were higher in presurgical samples and returned to normal following surgery. CONCLUSIONS: The proinflammatory cytokines IL-6 and IL-8, but not IL-1ß, were produced in greater amounts in papillary thyroid cancer. Serum neopterin seems to be a valid biological marker supporting the presence of papillary thyroid cancer.

Oxidative DNA damage: the thyroid hormone-mediated effects of insulin on liver tissue.

Thyroid hormone affects glucose homeostasis with its actions between the skeletal muscle and liver and the altered oxidative and non-oxidative glucose metabolism. In our study three chemicals are considered biomarkers associated with oxidative stress for protein modifications were measured; 8-hydroxy-2-deoxyyguanosine (8-OHdG), a major lesion that can be generated by reactive oxygen species for DNA damage, protein carbonyl content (PCO), products of protein oxidation and advanced oxidation protein products (AOPPs) a dithyrosine containing cross-linked protein products. The purpose of the recent study was to determine the effects of insulin and T4 or their combination in diabetic, thyroidectomized, or diabetic-thyroidectomized rats and possible relations with oxidative DNA and protein damages. For this purpose, rats were assigned to eight groups: Group 1; control, Group 2; diabetes, Group 3; diabetes+insulin, Group 4; surgically thyroidectomized control, Group 5; thyroidectomized+diabetes, Group 6; thyroidectomized+diabetes+insulin, Group 7; thyroidectomized+diabetes+insulin+thyroid hormone, levothyroxin sodium, 2.5 µg/kg and Group 8; thyroidectomized+diabetes+insulin+thyroid hormone, levothyroxin sodium, 5.0 µg/kg for 5 weeks. After the genomic DNA of liver tissues was extracted, the ratio of 8-OHdG to deoxyguanosine and liver tissue protein oxidation markers was determined. The main findings of our recent study were the increased 8-OHdG levels during the diabetes, hypothyroidism, and hypothyroidism with diabetes, which can be regulated in different percentages with the treatment of 2.5 and 5.0 µg/kg doses of thyroid hormone and the altered protein carbonyl and AOPP levels of liver tissue. Consequently, it was observed that the DNA and protein damage induced by oxidative stress in diabetes could be regulated by dose-dependent thyroid hormone-mediated effects to insulin treatment.

Leptin levels in thyroid cancer.

BACKGROUND: Leptin has physiological roles in multiple systems, and has possible effects on several carcinogenesis steps. The aim of this study was to investigate the leptin levels in thyroid papillary carcinoma (TPC) patients. METHODS: Forty-three female TPC patients and 30 healthy female control subjects were recruited for the study. TPC was diagnosed by fine needle aspiration biopsy. TPC patients had a bilateral total thyroidectomy operation and their leptin levels were measured before and 20 days after the operation. RESULTS: Serum leptin levels of TPC patients were higher than in control group subjects (21.15 +/- 14.12 ng/mL vs. 9.89 +/- 0.21 ng/mL, p < 0.05). The leptin levels decreased after total thyroidectomy (13.92 +/- 10.55 ng/mL) compared to prethyroidectomy levels (22.94 +/- 14.67 ng/mL) in 34 patients who came to the follow-up visit (p < 0.05). However, the decreased post-thyroidectomy levels of leptin were still statistically significantly higher than the control group levels. Multivariate regression analysis showed that the leptin levels in TPC patients were not related to age, menopausal status or pathologic occult status but were directly related to the cancer group. CONCLUSION: Leptin levels were elevated in thyroid cancer, decreased after total thyroidectomy, and might be associated with thyroid papillary carcinogenesis.

Oxidant/antioxidant balance in patients with thyroid cancer.

PURPOSE: To compare the antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the levels of lipid peroxidation product malondialdehyde (MDA) in blood samples of thyroid cancer patients compared to healthy controls. METHODS: 43 control subjects (mean age 44+/-13 years) and 43 patients (43+/-13 years) presented with multinodular goiter whose fine needle aspiration revealed malignant cytology were included into this study. The SOD, MDA and GSH-Px activities were measured in control subjects, and before/20 days after thyroidectomy in thyroid cancer patients. RESULTS: SOD activities of pre-thyroidectomy, post-thyroidectomy and control groups were not different (p>0.05). Before thyroidectomy GSH-Px activities were lower (p<0.05) and MDA levels were higher (p<0.05) than the control group. In post- thyroidectomy, GSH-Px activity (p<0.05) increased, and MDA levels (p<0.05) decreased compared to prethyroidectomy levels. After thyroidectomy GSH-Px activity was significantly higher than the control group (p<0.05). Although post-thyroidectomy MDA levels significantly decreased, they were still higher than the control group (p<0.05). CONCLUSION: The superoxide dismutase does not seem to change with thyroid cancer and thyroidectomy but both antioxidant glutathione peroxidase and lipid peroxidation product malondialdehyde do. These preliminary findings may point out oxidant/antioxidant imbalance associated with thyroid cancer.

The thyroid hormone mediated effects of insulin on serum leptin levels of diabetic rats.

In this study, we aimed to evaluate the possible relations of serum leptin and thyroid hormones on insulin treatment of surgically thyroidectomized and streptozotosin induced diabetic group of rats and whether the thyroid hormones control the leptin levels or leptin levels affect the thyroid hormones in DM. The Sprague-Dawley rats were assigned to eight groups: group 1, control; group 2, diabetes (injected intraperitoneally (i.p.) with streptozotocin (stz) 55 mg/kg); group 3, diabetes + insulin (rats were treated with insulin, 7-10 U/kg/day, subcutaneously); group 4, surgically thyroidectomized control; group 5, thyroidectomized + diabetes (3 weeks after the surgical operation, injected i.p. with stz); group 6, thyroidectomized + diabetes + insulin; group 7, thyroidectomized + diabetes + insulin + thyroid hormone (after diabetes induction, rats were treated with insulin and thyroid hormone, levothyroxin sodium (T4; 2.5 microg/kg); group 8, thyroidectomized + diabetes + insulin + thyroid hormone (T4; 5 microg/kg). The free and total T3 and T4 levels were measured in serum samples by otoanalyzer, and leptin levels were determined by ELISA method. The main finding of our recent study is that the decreased levels of serum leptin during the diabetes, hypothyroidism, and hypothyroidism with diabetes can be regulated in different percentages with the treatment of insulin and various doses of thyroid hormone. The observations in our study suggest the idea that during diabetic hypothyroidism, without thyroid hormone treatment, insulin is not sufficient to balance the metabolic pathways so mediated effects of insulin in leptin regulation via thyroid hormones are an increased possibility.

Advanced oxidation protein products, ferrous oxidation in xylenol orange, and malondialdehyde levels in thyroid cancer.

AIMS AND BACKGROUND: The oxidation of protein plays an essential role in the pathogenesis of an important number of degenerative and cancer diseases, which is now widely recognized. The aim is to examine advanced oxidation protein products (AOPPs), lipid peroxidation products malondialdehyde (MDA), and ferrous oxidation in xylenol orange (FOX) in blood samples of papillary thyroid cancer patients compared with healthy controls to determine the oxidation status and the change after thyroidectomy. METHODS: Thirty-five female thyroid cancer patients who underwent total thyroidectomy and 39 female control subjects were included into this study. Prethyroidectomy and postthyroidectomy, AOPP, FOX, and MDA levels were studied. RESULTS: Prethyroidectomy AOPP, FOX, and MDA levels were significantly higher compared to control (P < .05). In postthyroidectomy AOPP, FOX, and MDA levels were significantly decreased compared with prethyroidectomy levels (P < .05). However, postthyroidectomy levels on the 20th day were still significantly higher, compared to control subjects (P < .05). CONCLUSION: In conclusion, all of AOPP, FOX, and MDA levels that are markers of protein oxidation and lipid hyperoxidation may induce thyroid cancer development and begin to decrease after thyroidectomy.

Oxidant/antioxidant balance in patients with thyroid cancer

PURPOSE: To compare the antioxidant enzyme activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the levels of lipid peroxidation product malondialdehyde (MDA) in blood samples of thyroid cancer patients compared to healthy controls. METHODS: 43 control subjects (mean age 44±13 years) and 43 patients (43±13 years) presented with multinodular goiter whose fine needle aspiration revealed malignant cytology were included into this study. The SOD, MDA and GSH-Px activities were measured in control subjects, and before/20 days after thyroidectomy in thyroid cancer patients. RESULTS: SOD activities of pre-thyroidectomy, post-thyroidectomy and control groups were not different (p>0.05). Before thyroidectomy GSH-Px activities were lower (p<0.05) and MDA levels were higher (p<0.05) than the control group. In post- thyroidectomy, GSH-Px activity (p<0.05) increased, and MDA levels (p<0.05) decreased compared to prethyroidectomy levels. After thyroidectomy GSH-Px activity was significantly higher than the control group (p<0.05). Although post-thyroidectomy MDA levels significantly decreased, they were still higher than the control group (p<0.05). CONCLUSION: The superoxide dismutase does not seem to change with thyroid cancer and thyroidectomy but both antioxidant glutathione peroxidase and lipid peroxidation product malondialdehyde do. These preliminary findings may point out oxidant/antioxidant imbalance associated with thyroid cancer.