Enhanced Bone Healing Through Systemic Capsaicin Administration: An Experimental Study on Wistar Rats.

BACKGROUND The healing of bone defects is a serious challenge worldwide. One branch of dentistry deals with bone defects. Capsaicin has anti-inflammatory, anti-oxidative, and cholesterol-reducing effects. The aim of this study was to evaluate the effects of systemic capsaicin administered at different doses on bone healing. MATERIAL AND METHODS A total of 32 male wistar rats was used, their weight varying between 250 and 300 g. The rats were randomly divided into 4 groups of 8 rats each. The analyses served to evaluate the effect on healing of different doses of capsaicin and grafts. A significant increase was observed in the number of osteoblasts in the capsaicin-applied groups, compared with the control group. RESULTS The analyses served to evaluate the effect on healing of different doses of capsaicin and grafts. A significant increase was observed in the number of osteoblasts in the capsaicin-applied groups, compared with that of the control group. The inflammation scores showed a significant difference only in the control group and in the group administered with 50 mg/kg capsaicin (P=0.010). The osteoclast counts were significantly different between all groups. CONCLUSIONS As a result of the analyses, positive effects on bone healing were observed when capsaicin 0.25 mg/kg and 0.50 mg/kg was administered intraperitoneally. However, more studies are needed for more accurate information.

Do Histologically Aggressive Subtypes of Papillary Thyroid Microcarcinoma have Worse Clinical Outcome than Non-Aggressive Papillary Thyroid Microcarcinoma Subtypes? A Multicenter Cohort Study.

Histologically aggressive micropapillary thyroid carcinomas (PTMC) subtypes are thought to be associated with an aggressive clinical course. However, evidence for unfavorable clinical outcomes in patients with aggressive PTMC subtypes is not clear. In this study, we intended to determine the difference in clinical outcomes between patients with aggressive and non-aggressive PTMC subtypes. In this multicenter cohort study, the computer-recorded clinical and histopathological data of patients who underwent thyroid surgery between January 2000 - January 2021 in 9 referral centers and were diagnosed as PTMC were analyzed. A total of 1585 patients [female 1340 (84.5%), male 245 (15.5%), mean age 47.9±11.63 years), with a mean follow-up time of 66.55±37.16 months], were included in the study. Ninety-eight cases were diagnosed as aggressive and 1487 as non-aggressive subtypes. Persistent/recurrent disease was observed in 33 (33.7% )and 41 (2.8%) patients with aggressive and non-aggressive subtypes (p<0.001). Diseases-free survival rates were markedly lower in patients with aggressive than in those with non-aggressive PTMC subtypes (66.3 vs. 94.8%, log-rank p<0.001). Moreover, in multivariate analysis, aggressive histology was an independent predictor of persistent/recurrent disease, after controlling for other contributing factors (HR 5.78, 95% CI 3.32-10, p<0.001). Patients with aggressive PTMC subtypes had higher rates of incomplete biochemical and structural response than patients with non-aggressive subtypes as well (p<0.001). Aggressive PTMC subtypes share many characteristics with histologically identical tumors>1 cm in size. Therefore, the histopathological subtype of PTMC should be taken into consideration to tailor a personalized management plan.

Evaluation of the Effects of Dual Antiplatelet Therapy on Guided Bone Regeneration in Peri-Implant Bone Defect.

In this study, the authors aim to investigate the effect of dual antiplatelet agents on peri-implant-guided bone regeneraation by studying a sample of rats with titanium implants in their tibias. The rats were randomly divided into 5 groups: acetylsalicylic acid (ASA) (n=10), treated with 20 mg/kg of ASA; ASA+CLPD (Clopidogrel): (n=10), treated with 20 mg/kg of ASA and 30 mg/kg of clopidogrel; ASA+PRSG (Prasugrel): (n=10), treated with 20 mg/kg of ASA and 15 mg/kg of prasugrel; ASA+TCGR (Ticagrelor): (n=10), treated with 20 mg/kg of ASA and 300 mg/kg of ticagrelor; and a control group (n=10) received no further treatment after implant surgery. Bone defects created half of the implant length circumferencial after implant insertion and defects filled with bone grafts. After 8 weeks experimental period, the rats sacrified and implants with surrounding bone tissues were collected to histologic analysis; bone filling ratios of defects (%) and blood samples collected to biochemical analysis (urea, creatinine, aspartate aminotransferase, alanine aminotransferase, phosphorus, magnesium, alkaline phosphatase, calcium, and parathormone). A statistically significant difference was not detected between the groups for all parameters ( P >0.05). When the percentage of new bone formation was examined, it was found that there was no statistically significant difference between the groups ( P >0.05). Antiplatelet therapy may not adversely affect guided bone regeneration in peri-implant bone defects.

Prognostic value of indoleamine 2, 3-dioxygenase-1 expression in glial tumors.

Background and purpose:

Gliomas are the most common primary malignant central nervous system tumors in adults, exhibiting a poor prognosis. Indoleamine 2, 3-dioxygenase-1 (IDO-1) has important functions in cancer immunotherapy due to its role in escaping cancer cells from the immune system. In this study we purposed to evaluate the correlation between IDO-1 expression and clinicopathological parameters in gliomas, and whether IDO-1 can be a prognostic marker.

n=75 patients in total, n=25 patients with low grade glial tumors (LGG, grade 1-2), n=25 patients with high grade glial tumors (HGG, grade 3-4), and n=25 persons with normal brain tissue as control group were included in this study. IDO-1 expression was categorized by using immunohistochemical staining in biopsy specimens as high (H) and low (L) groups among the patients with gliomas. We used a 95% percent confidence interval and p <0.05 to analyze the association between the degree of IDO-1 expression, clinicopathological characteristics, and survival rates in glioma patients. 

In HGG, IDO-1 levels were higher than in control brain tissue and LGG (p< 0.001). The mean overall survival (OS) was longer in the L-IDO-1 group (64.53 ± 3.34) in months (95% CI: 57.969-71.098) compared to the H-IDO-1 group (43.74 ± 4.36) in months, (95% CI: 35.218-52.330) (p< 0.05).

IDO-1 expression is an in­de­pendent prognostic biomarker to predict 
OS and progression in HGG. IDO-1 can be evaluated as an alternative instrument for precision medicine in the treatment of gliomas.

Irisin Improves High-Fat Diet-Induced Sexual Dysfunction in Obese Male Rats.

INTRODUCTION: Obesity is known to cause sexual dysfunction including erectile dysfunction and poor semen quality. Lifestyle modifications such as exercise have increasingly been more recognized to lower the likelihood of having sexual dysfunction or infertility in obese men. In this context, as an exercise-mimetic hormone, irisin has a potential to improve obesity-related reproductive dysfunctions. We aimed to elucidate possible effects of irisin on high-fat diet (HFD)-induced reproductive dysfunction in obese male rats. METHODS: Rats were divided into four groups: vehicle, irisin, obese, and obese + irisin. The rats in obese and obese+irisin groups were fed with HFD (60% kcal fat) pellets for 12 weeks to induce obesity, and then obesity-induced sexual dysfunction was confirmed by the sexual behavior test (SBT). Irisin and obese+irisin groups received irisin (100 ng/kg/day) infusion by an s.c. osmotic minipump for 4 weeks after HFD-induced obesity was formed. RESULTS: Irisin did improve a number of measures of copulation, including penile erection, ejaculation, and sexual performance, and also improved sperm morphology and motility and decreased fat-induced testicular damage. It decreased serum leptin levels. On the other hand, irisin did not affect serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone. It also increased gene expression of tyrosine hydroxylase (TH) and adrenoceptor alpha 1A (ADRA1A) in the medial preoptic area (mPOA) and nucleus accumbens (NAc). CONCLUSION: Irisin provided a marked enhancement of HFD-induced decrease in libido, potency, sexual performance, and erection in SBT. Taken together, our results emphasize that irisin has a restorative and improver role in HFD-induced reproductive dysfunctions in obese male rats.

Evaluation of the Effects of Systemic Irisin Application on Guided Bone Regeneration in Peri-implant Bone Defects.

This study aimed to investigate the effects of systemic irisin hormone application on new bone formation in peri-implant bone defects. After surgically creating peri-implant bone defects in the metaphyseal part of the tibiae of rats, the rats were randomly divided into 2 equal groups: a control group and an irisin group. In the control group, the rats received no further treatment during the 4-week experimental period after the surgery. The rats in the irisin group, 100 ng/kg irisin was administered intraperitoneally 3 days a week during the 8 weeks experimental period after the surgery. At the end of the experimental period, the rats were euthanized. Implants and surrounding bone tissues were collected for histological new bone formation analysis. The Student t test was used for statistical analysis. There were no significant differences between the groups in the histological analysis, new bone formation and fibrosis (P>0.05). Also, in the irisin group, there was numerically but not statistically more new bone formation detected compared with the controls. Within the limitations of this study, irisin did not affect new bone formation in peri-implant defects, although the numerical values favored the irisin group.

Evaluation of the Effects of Topical Application of Chlorhexidine, Ozone, and Metronidazole on Palatal Wound Healing: A Histopathological Study.

ABSTRACT: This study aimed to evaluate the effects of chlorhexidine, metronidazole, and ozone application on the healing of palatal wounds in diabetic rats. A defect in the form of a 4 mm-diameter wound was created on the palatal mucosa of 84 adult female Wistar albino rats, which were randomly divided into 4 groups: control, chlorhexidine, metronidazole, and ozone groups. The animals were euthanized after 3, 6, and 10 days, and wound closure was histologically assessed. On day 3, polymorphonuclear leukocytes were significantly higher in the control group than in the chlorhexidine and ozone groups ( P < 0.05). Fibrosis was higher in the ozone group than in the control and chlorhexidine groups ( P < 0.05). Vascular endothelial growth factor was higher in the metronidazole and ozone groups than in the control group ( P < 0.05). On day 6, the quantity of polymorphonuclear leukocytes was higher in the control, metronidazole, and chlorhexidine groups than in the ozone group ( P < 0.05). Vascular endothelial growth factor was higher in the ozone group than in the control, chlorhexidine, and metronidazole groups ( P < 0.05). On day 10, Vascular endothelial growth factor was higher in the control, chlorhexidine, and metronidazole groups than in the ozone group ( P < 0.05). The authors concluded that the use of chlorhexidine, ozone, and metronidazole pastes resulted in enhanced wound healing, as determined histologically.The authors suggest that ozone supplementation can be an alternative therapy to chlorhexidine in impaired wound healing in diabetes mellitus.

The effect of caffeic acid phenethyl ester and Ankaferd Blood Stopper on the diabetic and nondiabetic gingival wound healing: an experimental study

Background/aim: Healthy wound healing is very important for patient comfort. Diabetes is one of the factors that negatively affect wound healing. Ankaferd Blood Stopper (ABS) and caffeic acid phenethyl ester (CAPE) are antiinflammatory and antimicrobial agents and may have positive effects on wound healing. Materials and methods: In this study, 72 male Wistar albino rats were used. Rats; control, CAPE, ABS, diabetes + control, diabetes + ABS and diabetes + CAPE groups were divided into 6 groups. A healthy 36 rats created diabetes using streptozotocin (STZ). A gingival wound was created using a 4-mm punch biopsy in the gingival tissue under the lower anterior incisors of the rats. Results: The comparison between the nondiabetic groups had a statistically significant positive effect compared to the control group of CAPE and ABS (P ˂ 0.05). In the comparison between ABS and diabetes + ABS groups and in the comparison between CAPE and diabetes + CAPE groups, a decrease in vascularization in diabetes + CAPE groups was observed and it was statistically significant (P ˂ 0.005). Conclusion: ABS and CAPE have been found to have positive effects on gingival wound healing in the nondiabetic group. We think that this situation is caused by its antiinflammatory and antimicrobial properties.

Intratumoral Cytotoxic T-Lymphocyte Density and PD-L1 Expression Are Prognostic Biomarkers for Patients with Colorectal Cancer.

Background and objectives: Cytotoxic T-lymphocyte (CTL)-mediated inflammatory response to tumors plays a crucial role in preventing the progression of some cancers. Programmed cell death ligand 1 (PD-L1), a cell-surface glycoprotein, has been reported to repress T-cell-mediated immune responses against tumors. However, the clinical significance of PD-L1 in colorectal cancer (CRC) remains unclear. Our aim was to elucidate the prognostic significance of PD-L1 expression and CD8+ CTL density in CRC. Materials and methods: CD8 and PD-L1 immunostaining was conducted on 157 pathologic specimens from patients with CRC. The CD8+ CTL density and PD-L1 expression within the tumor microenvironment were assessed by immunohistochemistry. Results: Tumor invasion (pT) was significantly correlated with intratumoral (p = 0.011) and peritumoral (p = 0.016) CD8+ CTLs density in the tumor microenvironment. In addition, there was a significant difference in the intensity of CD8+ CTLs between patients with and without distant metastases (intratumoral p = 0.007; peritumoral p = 0.037, T-test). Lymph node metastasis (pN) and TNM stage were significantly correlated with PD-L1 expression in CRC cells (p = 0.015, p = 0.029, respectively). Multivariate analysis revealed a statistically significant relationship between the intratumoral CD8+ CTL density and disease-free survival (DFS) (hazard ratio [HR] 2.06; 95% confidence interval [CI]: 1.01-4.23; p = 0.043). The DFS was considerably shorter in patients with a high expression of PD-L1 in cancer cells than those with a low expression (univariate HR 2.55; 95% CI 1.50-4.34; p = 0.001; multivariate HR 0.48; 95% CI 0.28-0.82; p = 0.007). Conversely, patients with high PD-L1 expression in tumor-infiltrating lymphocytes had a longer DFS in both univariate analysis (HR 0.25; 95% CI: 0.14-0.44; p < 0.001) and multivariate analysis (HR 3.42; 95% CI: 1.95-6.01; p < 0.001). Conclusion: The CD8+ CTL density and PD-L1 expression are prognostic biomarkers for the survival of patients with CRC.

Is there any difference between endometrial hyperplasia and endometrial carcinoma in terms of expression of TRPM2 and TRPM7 ion channels?

Background/aim: This study compared TRPM2 and TRPM7 ion channel gene expression and immunohistochemical staining in endometrial hyperplasia and endometrium adenocarcinoma. Materials and methods: Sections were taken from paraffin blocks of 120 patients who were divided into 6 groups as follows: G1 (n = 20), proliferative endometrium (PE); G2 (n = 20), EH without atypia; G3 (n = 20), EH with atypia; G4 (n = 20), stage 1A, grade 1 EC; G5 (n = 20), stage 1A, grade 2 EC; and G6 (n = 20), stage 1A, grade 3 EC. TRPM2 and TRPM7 genes were analyzed with qRT-PCR in paraffin-embedded tissue samples. Under light microscopy, TRPM2 and TRPM7 immunostaining scores of the samples taken from polylysine slides were evaluated. Results: Compared to G1, TRPM2 mRNA gene expression was significantly downregulated in G3 and G5. TRPM2 immunoreactivity scores were similar in all groups. TRPM7 mRNA gene expression was significantly downregulated in G2, G3, and G6 when compared to G1. TRPM7 immunoreactivity scores were similar in G1, G2, and G3, but significantly decreased in G4, G5, and G6 Conclusion: Reduction in TRPM7 ion channel activity may be a progression marker for endometrial hyperplasia regardless of the atypical criteria.

Comparison of Osseointegration of Five Different Surfaced Titanium Implants.

The topography, chemical features, surface charge, and hydrophilic nature of titanium implant surfaces are crucial factors for successful osseointegration. This study aimed to investigate the bone implant contact (BIC) ratio of titanium dental implants with different surface modification techniques using the rat femoral bone model. Sandblasted and acid washed (SL-AW), sandblasted (SL), resorbable blast material (RBM), microarc (MA), and sandblasted and microarc (SL-MA) surfaces were compared in this study. Forty male Sprague-Dawley rats were used in this study. The rats were divided into 5 equal groups (n = 8), and totally 40 implants were integrated into the right femoral bones of the rats. The rats were sacrificed 12 weeks after the surgical integration of the implants. The implant surface-bone tissue interaction was directly observed by a light microscope, and BIC ratios were measured after the nondecalcified histological procedures. Bone implant contact ratios were determined as follows: SL-AW: 59.26 ±â€Š14.36%, SL: 66.01 ±â€Š9.63%, RBM: 63.53 ±â€Š11.23%, MA: 65.51 ±â€Š10.3%, and SL-MA: 68.62 ±â€Š6.6%. No statistically significant differences were found among the 5 different surfaced titanium implant groups (P > 0.05). Our results show that various implant surface modification techniques can provide favorable bone responses to the BIC of dental implants.

The effects of sclerotherapy with 5% trichloroacetic acid on the cyst diameter and ovarian tissue in the rat ovarian cyst model.

The aim of this study was to compare the effects of only aspiration with aspiration and 5% trichloroacetic acid (TCA) application on ovarian cyst size and ovarian reserve. The ovarian cysts of 14 rats that were divided into two groups randomly were investigated after total salpingectomy procedure. G1 was the group of saline application after cyst aspiration, while in G2, after aspiration 5% TCA at half amount of aspiration volume was injected into the cyst and re-aspirated after five minutes. The abdomens of the rats were closed and re-explored after 1 month. The cyst diameters of the rats in each group were measured. Ovaries were removed for histopathological examination. There was no significant difference in cyst diameter in G1 before and after aspiration. In G2, there was a significant decrease in cyst size after TCA application. Ovarian follicle counts were not significantly different between the two groups. In conclusion, application of 5% TCA to the ovarian cysts for five minutes significantly reduces the cyst size. Impact Statement What is already known on this subject: Minimally invasive therapies come into prominence to avoid surgical complications and diminished fertility in the treatment of ovarian cysts. USG-guided aspiration and sclerosis has been reported as cost-efficient and effective treatment methods for localised benign cysts in other organs such as the thyroid, parathyroid, liver, kidney and spleen. It has been shown that sclerotherapy applied to infertile women with ovarian cysts reduces pelvic pain without affecting the number of follicles, term pregnancy and abortion rates, extracted oocytes, embryo quality or hormonal levels when compared to non-ovarian cystic infertile women. TCA is a chemical agent that is topically applied, not systemically absorptive, which causes denaturation of proteins and structural cell death, resulting in coagulation necrosis after chemical cauterisation. For this reason, we used 5% TCA to treat simple ovarian cysts on a rat model. What the results of this study add: In this experimental study, we showed that the application of 5% TCA into the cyst for five minutes - then aspirated - significantly reduced the size of the ovarian cysts. Five percent TCA application did not affect the ovarian reserve. What the implications are of these findings for clinical practice and/or further research: Our study is original because of the fact that to the best of our knowledge, this is the first study about the use of 5% TCA in treatment of ovarian cysts in the literature.

Comparison of the Effects of Local and Systemic Zoledronic Acid Application on Mandibular Distraction Osteogenesis.

Bisphosphonates are antibone resorptive drugs that are used to prevent bone tissue resorption in several skeletal diseases. The aim of this study was to examine the effects of systemic and local applications of zoledronic acid (ZA) on newly regenerated bone in a model of experimental distraction osteogenesis (DO). To do this mandibular DO was applied to 30 adult female Sprague Dawley rats, which were randomly divided into 3 groups: control, DO only, systemic zoledronic acid (SZA), and local zoledronic acid (LZA). In the LZA group, the gap between the bone fragments was filled with a gelatin sponge soaked in 2 mg of ZA and 0.1 mL of sterile saline. In the SZA group, a single dose of 0.1 mg/kg ZA was administered systemically. After the surgery, there was a 5-day latent waiting period and 10-day distraction phase. Following a 28-day consolidation period, the rats were euthanized and their mandibles were collected. The distracted bone area was seen to be filled with newly regenerated bone tissue in all 3 groups, both histologically and histomorphometrically. In addition, amounts of new bone formation, osteoblast cella, osteoclast (OC) cells, osteopontin, and vascular endothelial growth factor in the SZA and LZA groups were found to be higher when compared with the controls. Furthermore, in the SZA group, new bone formation, osteoblast, OC, osteopontin, and vascular endothelial growth factor were detected in significant amounts compared with the LZA group. Osteoclast numbers did not differ in a statistically significant manner in the SZA group with respect to the LZA group. Based on the results of this study, systemic and local applications of ZA could increase the formation of new bone in patients of DO, and systemic application is a more effective method compared with local application.

Predictive value of stathmin-1 and osteopontin expression for taxan resistance in metastatic castrate-resistant prostate cancer.

OBJECTIVE: Several pathways are known to be activated during metastasis and treatment of cancer. We investigated the role of osteopontin (OPN) and stathmin-1 (STHMN1) in metastatic castrate-resistant (mCRPC). METHODS: We included 30 patients who received at least 6 cycles of taxane regimen for metastatic mPC in the present study. For this study retrospective data was taken from Firat University, Faculty of Medicine, Medical Oncology Department between 2009 and 2015. OPN expression and STHMN1 expression were retrospectively evaluated by immunohistochemical staining in biopsy specimens. The relationship between the expression levels of OPN and STMN1 and the response to taxane based regimen and survival was analyzed. RESULTS: There was mild or strong overexpression of OPN and STHMN1 in all the patients. STHMN1 expression was mildly positive (+2) in four of the cases (13.2%) while it was strongly positive (+3) in 25 (83.4%) cases. Similarly, OPN expression was mildly positive (+2) and strongly positive (+3) in five (16.6%) and 25 (87.4%) patients, respectively. There was no significant correlation between the expression levels of STHMN1 and OPN, survival, and response to taxane based regimen (p>0.05); however, OPN overexpression showed a significant correlation with lower Gleason scores (GS) (p:0.032). CONCLUSIONS: STHMN1 and OPN may be prognostic markers although they are not predictive markers of response to treatment in mCRPC. The overexpression of OPN may help identifying patients with lower GS.

The Effect of Ozonated Olive Oil on Neovascularization in an Experimental Skin Flap Model.

OBJECTIVE: Angiogenesis is an important factor for flap viability. It has been reported that ozonated oil contributed to improved neovascularization in an acute cutaneous wound healing model. This study was undertaken to evaluate the effect of ozonated olive oil on vascular endothelial growth factor (VEGF)-mediated neovascularization of skin flaps in rats. STUDY DESIGN: A skin flap model was established in 21 rats and evaluated within 3 groups. No treatment was given to the rats in group 1. Olive oil and ozonated olive oil were topically applied (twice daily) to the flap surface for 7 days in groups 2 and 3, respectively. Immunohistochemical staining was performed to analyze the expressions of VEGF and CD34. RESULTS: The mean numbers of VEGF- and CD34-positive staining microvascular structures were 8.86 (SD, 1.35) and 10.29 (SD, 1.80) in group 1, 15.00 (SD, 1.41) and 15.57 (SD, 1.72) in group 2, and 25.14 (SD, 2.41) and 25.00 (SD, 2.16) in group 3. The VEGF and CD34 expressions in group 3 were significantly higher than those in group 2 (P < .001). Their expressions in group 2 were significantly higher than those in group 1 (P < .001). CONCLUSIONS: Both ozonated olive oil and olive oil improved neovascularization when they were topically applied on skin flaps. The effect of ozone was more prominent.

Investigation of Trpa1 and Trpc1 Immunreactivities in Colon Adenocarcinomas.

Purpose: As the normal colon epithelium differentiates into adenoma, invasive cancer and metastatic cancer, the cell acquires new characteristics such as apoptosis, proliferation, differentiation, invasion and metastasis. Many mechanisms are effective in acquiring these qualities. One of these is the regulation of the functioning of ion channels. This study aimed to examine TRPA1 and TRPC1 expression in colorectal adenocarcinomas showing different degrees of differentiation. Patients and Methods: We examined the biopsy specimens of 60 patients diagnosed with colorectal adenocarcinomas, including those of patients with well-differentiated (n = 20), moderately differentiated (n = 20) and poorly differentiated (n = 20) carcinomas. Moreover, 20 biopsy specimens of individuals with normal colonic mucosa were examined. Histoscores were calculated for TRPA1 and TRPC1 based on the extent of diffusion and intensity of immunoreactivity, and these scores were compared statistically. Results: A statistically significant increase in both TRPA1 and TRPC1 immunoreactivity was observed in low-grade and high-grade colon adenocarcinomas compared to the control group (p<0.001). A statistically significant decrease in both TRPA1 and TRPC1 immunoreactivity was observed in high-grade colon adenocarcinomas compared to low-grade colon adenocarcinomas (p<0.001). Conclusion: TRPA1 and TRPC1 immunoreactivites are increased in colorectal adenocarcinoma tissue compared with the healthy tissue. Furthermore, the immunoreactivity decreases as the grade of cancer increases.

Investigation of Hyaluronan Synthase 2 and CD44 immune reactivity as a biomarker to predict Progesterone-Resistant Endometrial Hyperplasia without atypia: A retrospective case-control study.

BACKGROUND/AIMS: In our study, the effect of hyaluronan synthase 2 (HAS2) and CD44 immunoreactivity as a predictive biomarker in the prediction of progesterone-resistant endometrial hyperplasia (EH) cases without atypia was investigated. SETTINGS AND DESIGN: In this retrospective study, HAS2 and CD44 immunoreactivity in the endometrial tissues of 60 patients diagnosed with EH and treated with progesterone and 20 patients diagnosed with proliferative endometrium (PE) were evaluated. MATERIALS AND METHODS: Eighty patients were divided into four groups. Group 1 (G1) (n = 20) = PE group, G2 (n = 20) = EH group without atypia, G3 (n = 20) = group with continued EH with treatment, G4 (n = 20) = EH with treatment without atypia. STATISTICAL ANALYSIS: Intergroup evaluation was done with One-way ANOVA and posthoc tukey test. P < 0.05 values were considered statistically significant. RESULTS: The HAS2 immunoreactivity score of G2 and G3 was higher than G1 and G4. On the other hand, there was no difference between G1 and G4. When G2 and G3 were compared, HAS2 immunoreactivity scores were significantly increased in G3. When CD44 immunoreactivity was compared with G1, a significant increase was detected in G2, G3, and G4. However, CD44 immunoreactivity scores were similar in G2, G3, and G4. CONCLUSION: HAS2 immunoreactivity may be an immunohistochemical biomarker in predicting EH cases without atypia resistant to progesterone therapy. Since CD44 immunoreactivity is increased in all EH groups without atypia, it is not effective in predicting treatment resistance.

The knockdown of stathmin with si-RNA inhibits invasion of mesothelioma.

BACKGROUND: To investigate the mechanism of action of stathmin1 (STMN1) in mesothelioma (MSM) and whether it has any role in its treatment. METHODS: STMN1 expression was examined using immunohistochemistry in biopsy tissues taken from MSM patients. The relationships between the levels of STMN1 expression in the pathology preparations of MSM patients, and the clinicopathological characteristics of these patients, and their survival times were investigated. Transfection of STMN1-specific siRNA into SPC212 cells was compared to negative control siRNAs. The mRNA levels of genes that may play a role in invasion, apoptosis, and autophagy were evaluated by RT-PCR. RESULTS: The expression of STMN1 was shown to be high in MSM tissues (p < 0.05). It was found that the only independent predictor factor affecting the survival time of MSM patients was the disease stage (p < 0.05). STMN1 was significantly reduced after siRNA intervention (81.5%). STMN1 with specific siRNA has been shown to suppress invasion by reducing the mRNA levels of cadherin-6 (CDH6), fibroblast growth factor-8 (FGF8), hypoxia-inducible factor 1 (HIF1A), matrix metallopeptidase 1-2 (gelatinase A) (MMP1-2), and TIMP metallopeptidase inhibitor 2 (TIMP2), which are important markers for invasion. Although the expression of apoptosis and autophagy-related genes, caspase-2 (Casp2) and LC-3, was reduced by silencing STMN1 with specific siRNA in western blot analysis, this effect was not observed in PCR results. CONCLUSIONS: Immunohistochemical analysis of STMN1 may contribute to the differential diagnosis of MSM, and STMN1 may also be considered as a potential therapeutic target in the early invasive stage of MSM therapy.

The overexpression of cyclin D1 is a positive prognostic factor in advanced-stage breast carcinoma cases.

OBJECTIVE: Cyclin D1 (CDDN1) is a protein required for mitotic cell cycle progression through the G1 phase, as well as a regulatory component of the cyclin-dependent kinases CDK4 and CDK6. In this study, we wanted to evaluate the relationship between CDDN1 expression and clinicopathological features in breast cancer (BC) cases and whether CDDN1 could be used as a prognostic biomarker for BC cases. METHODS: A total of 70 cases, 30 cases each with limited and advanced-stage BC, and as the control group, 10 healthy breast tissue, without a cancer diagnosis, with examined for benign reasons (mammoplasty, breast reduction surgery, etc.) were included in this study. The pathological specimens from the cases were stained, immunohistochemically, and categorized as a "low" (L) group or a "high" (H) group for CDDN1 expression. The cases' clinicopathological features and survival rates were evaluated statistically, within a 95% of confidence interval, p<0.05, retrospectively. RESULTS: The median follow-up period of the cases was 48.00 (range, 6-150) months. CDDN1 expression was significantly higher in advanced-stage BC cases than in normal breast tissue and limited-stage BC cases. The median overall survival (OS) was 96 months (CI 95%: 67.74-117.59) in the H-CDDN1 group, compared to the L-CDDN1 group not reached, but there was no relation (p>0.05). CDDN1 overexpression was more prominent in low-grade advanced BC cases (p=0.004). The median OS of advanced-stage BC cases with Grade 1 was significantly longer than those with other grades (p=0.04). CONCLUSION: Our results suggest that CDDN1 expression can be used as a potentially appropriate positive prognostic biomarker for advanced-stage BC cases.

Fibulin1 and mesothelin expressions in pancreas ductal adenocarcinoma.

OBJECTIVE: The balance between malignant tumor cells and the connective tissue surrounding them determines the aggressiveness of the tumor. We aimed to understand the effects of mesothelin (MSLN) and fibulin1 (FBLN1) expressions on survival in pancreas ductal adenocarcinoma (PDCA), and also whether these proteins have prognostic value for PDCA. METHODS: Of 80 patients in total, 40 who underwent the Whipple procedure for diagnosed PDCA between 2009 and 2016, and 40 patients with diagnosed pancreatitis as the control group, were included in the present study. Immunohistochemically, MSLN, and FBLN1 expressions were evaluated retrospectively. We assessed the relationship between the degree of MSLN, FBLN1 expression, clinical-pathological features, and survival rates in PDCA cases. RESULTS: The median follow-up duration was 11.4 (3-41) months. All of the patients for MSLN and FBLN1 were immune reactive. We detected a significant difference in MSLN expression between patients with PDCA and control groups, but not in FBLN1 expression. MSLN, FBLN1 expressions were categorized as lower-higher (L/H) groupings. There was no difference in the median overall survival (OS) of patients in the MSLN groups. The L-FBLN1 group had a median OS of 18 months (95% CI: 9.51-26.48) versus 14 months (95% CI: 13.021-14.97) in the H-FBLN1 group (interconnective tissue) (p=0.035). According to Kaplan-Meier analysis, L-FBLN1 expression in the tumor microenvironment was associated with longer survival in PDCA. The FBLN1 expression in the tumor microenvironment was shown to be significantly inversely related to OS (p=0.05). CONCLUSION: The FBLN1 expression, which is in the tumor microenvironment of PDCA, may serve as a prognostic biomarker.