Immunohistochemical and molecular evaluation of TUSC2 expression in breast cancer.

OBJECTIVE: Tumor suppressor candidate 2 has shown to be deleted in lung, colon, and bladder cancer types. In the present study, we aimed to investigate the expression of TUSC2 in breast cancer. MATERIALS AND METHODS: A total of thirty patients with breast cancer were included in the study. Normal and tumor tissue samples from fresh mastectomy materials were stored at -80 C until the number of cases was completed for gene expression analysis. Histopathological examination was carried out with routine hematoxylin & eosin method. TUSC2 staining was performed for immunohistochemical analysis. RESULTS: The tumors of thirteen patients were Luminal A, fourteen patients were Luminal B, one patient was cerbB2(+), and tumors of two patients were triple-negative. Ki67 proliferation index was less than 14% in fifteen cases and tumor size was less than 2 cm in seven cases. Lymphovascular invasion and lymph node metastasis were present in thirteen cases. Statistically, TUSC2 expression significantly decreased or was lost in breast tumor tissues compared to normal tissues (p < 0.0001). TUSC2 expression decreased as the Ki67 proliferation index increased (p = 0.0003), and TUSC2 expression decreased as tumor size increased (p = 0.0483). The loss or decrease in the TUSC2 expression was significant as the tumor grade increased (p = 0.3740). Gene expression analysis correlated with immunohistochemistry results. CONCLUSION: The results of the present study demonstrated a decrease or loss of TUSC2 expression in breast cancer tissue compared to normal tissue. A correlation was found between TUSC2 expression and Ki67 proliferation index and tumor size.

Targeting Breast Cancer with N-Acetyl-D-Glucosamine: Integrating Machine Learning and Cellular Assays for Promising Results.

BACKGROUND: Breast cancer is a common cancer with high mortality rates. Early diagnosis is crucial for reducing the prognosis and mortality rates. Therefore, the development of alternative treatment options is necessary. OBJECTIVE: This study aimed to investigate the inhibitory effect of N-acetyl-D-glucosamine (D-GlcNAc) on breast cancer using a machine learning method. The findings were further confirmed through assays on breast cancer cell lines. METHODS: MCF-7 and 4T1 cell lines (ATCC) were cultured in the presence and absence of varying concentrations of D-GlcNAc (0.5 mM, 1 mM, 2 mM, and 4 mM) for 72 hours. A xenograft mouse model for breast cancer was established by injecting 4T1 cells into mammary glands. D-GlcNAc (2 mM) was administered intraperitoneally to mice daily for 28 days, and histopathological effects were evaluated at pre-tumoral and post-tumoral stages. RESULTS: Treatment with 2 mM and 4 mM D-GlcNAc significantly decreased cell proliferation rates in MCF-7 and 4T1 cell lines and increased Fas expression. The number of apoptotic cells was significantly higher than untreated cell cultures (p < 0.01 - p < 0.0001). D-GlcNAc administration also considerably reduced tumour size, mitosis, and angiogenesis in the post-treatment group compared to the control breast cancer group (p < 0.01 - p < 0.0001). Additionally, molecular docking/dynamic analysis revealed a high binding affinity of D-GlcNAc to the marker protein HER2, which is involved in tumour progression and cell signalling. CONCLUSION: Our study demonstrated the positive effect of D-GlcNAc administration on breast cancer cells, leading to increased apoptosis and Fas expression in the malignant phenotype. The binding affinity of D-GlcNAc to HER2 suggests a potential mechanism of action. These findings contribute to understanding D-GlcNAc as a potential anti-tumour agent for breast cancer treatment.

Anti-Inflammatory Effect of Dental Pulpa Mesenchymal Stem Cell Exosomes Loaded Mucoadhesive Hydrogel on Mice with Dental Nickel Hypersensitivity.

In this study, the anti-inflammatory effect of dental pulp mesenchymal stem cell (MSCs) exosomes loaded to mucoadhesive hydrogel is investigated in a dental nickel hypersensitivity murine model. After culture of dental pulp MSCs in the third passage MSCs are loaded to a mucoadhesive hydrogel based on chitosan, cross-linked with genipin and modified with catechol groups. A dental nickel hypersensitivity model is created by administering NiCl2 and 10 µg mL-1 lipopolysaccharide to 4-6 week-old Balb-c mice by intradermal injection. In mice treated with dental pulp MSC exosomes and exosomes in hydrogel, interferron gamma (IFN-γ) secreting CD4+T lymphocyte ratios significantly increase compared to the untreated group (p < 0.05). IFN-γ and interleukin 10 (IL-10) expression in buccal mucosa tissue sections and IFN-γ secreting CD4+T lymphocyte ratios are found to be significantly higher in mice treated with dental pulpa MSCs (DPMSCs) exosomes and DPMSCs exosomes in hydrogel compared to the untreated group (p < 0.05). According to flow cytometry results, IL-4 secreting CD4+T lymphocytes are found to be significantly decreased in DPMSCs exosomes group compared to dental nickel hypersensitivity group (p < 0.05). Administration of DPMSCs exosomes with mucoadhesive hydrogel may be an alternative to current medication in the treatment of dental nickel hypersensitivity.

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.

The role of Wnt pathway antagonists in early-stage lung adenocarcinoma.

PURPOSE: We aimed to examine the expression levels of the genes encoding adenomatous polyposis coli (APC) 1, APC-2, Dickkopf related protein (DKK)-1, DKK-3, secreted frizzled-related protein (SFRP)-2, SFRP-4, and SFRP-5, which play roles in the Wnt signaling pathway, in lung adenocarcinoma and adjacent normal lung tissues and to evaluate their relationships with clinicopathologic factors. MATERIALS AND METHODS: The expression levels of genes in formalin-fixed paraffin-embedded samples of tumor tissue and adjacent intact lung tissue from 57 patients who underwent surgery for lung adenocarcinoma between 2011 and 2018 were determined by real-time PCR analysis. RESULTS: The expression levels of the DKK-1 in tumor tissue, especially in stage I-II tumor tissue, were significantly suppressed compared to those in normal tissue (p < 0.025). Whereas DKK-1 expression was suppressed in the tumor tissue of patients with early-stage lung adenocarcinoma, expression of the SFRP-5 in these patients was significantly higher in tumor tissue than in normal tissue (p < 0.039). CONCLUSION: In our study, opposing regulation was found between the SFRP-5 and DKK-1, which are known to be extracellular antagonists of the Wnt signaling pathway. The SFRP-5 was found to have an oncogenic role in adenocarcinoma development. Studies of the opposing regulation between these genes in early-stage lung adenocarcinoma may shed light on the mechanisms associated with the development of carcinogenesis. The relationships or interactions of these genes may serve as potential therapeutic targets.

Is There any Relationship Between Granulomatous Mastitis and Seasons? An Analysis of Seasonal Frequency, Clinical, and Radiologic Findings.

OBJECTIVE: Idiopathic granulomatous mastitis (IGM) is a rare, resistant, and recurrent benign disease of the breast. IGM can be clinically and radiologically confused with breast carcinoma, and core needle biopsy is needed to diagnose. The etiology and pathogenesis of IGM have not been fully explained. This premenopausal disease may be associated with pregnancy, breastfeeding, autoimmune processes, inflammation, and oral contraceptives. However, there is no study on whether there is a seasonal relationship. MATERIALS AND METHODS: From January 2015 to January 2020, the seasonal relationship of IGM was evaluated in 37 females aged between 25-49. RESULTS: Although all cases were distributed between September and May, there was no statistically significant result in the relationship with the season. US is the main modality in the diagnosis of this condition which only provides an accurate pre-diagnosis approach with the typical USG appearance features. Some MRI features may help us to distinguish IGM from breast malignities. CONCLUSION: IGM is a rare chronic non-specific inflammatory lesion of the breast, which can be confused with benign and malignant breast diseases in both clinical and radiologic aspects. To understand the etiology of this condition better, the seasonal connection needs to be evaluated in larger patient groups.

Diagnostic Value of MiR-125b as a Potential Biomarker for Stage I Lung Adenocarcinoma.

BACKGROUND: We aimed at exploring biological functions of differentially expressed miRNAs during carcinogenesis, to identify miRNAs dysegulations involved in DNA repair mechanisms, and to evaluate potential of miRNAs as prognostic and diagnostic biomarkers for early lung adenocarcinomas (LAC). METHODS: We obtained 21 LAC and paired adjacent normal formalin-fixed, paraffinembedded lung tissues from patients who underwent curative resection for stage I LAC. We compared expression levels of eight miRNAs involved in the DNA repair mechanism between LAC and adjacent tissues. RESULTS: Expressions of Hsa-miR-9-5p, hsa-miR-24-3p, hsa-miR-125a-3p, hsa-miR- 125b-5p, hsa-miR-155-5p, and hsa-let-7a-5p were significantly up-regulated in stage I LAC tissues compared with those in the adjacent tissues. In addition, expressions of hsa-mir-9-5p, hsa-mir-24-3p, hsa-mir-125a-3p, hsa-mir-125b-5p, and hsa-mir-155-5p were significantly up-regulated in stage Ia LAC tissues, whereas expressions of hsa-mir- 125a-3p and hsa-mir-125b-5p were significantly up-regulated in stage Ib LAC tissues. Receiver operating characteristic (ROC) analysis revealed that AUROC of hsa-mir-125b- 5p was 0.875 (P < 0.001). CONCLUSION: Expression of hsa-mir-125b-5p could be used to distinguish LAC from adjacent tissues. Our result suggests that hsa-mir125b-5p can be a prognostic and diagnostic biomarker for LAC.

Protective Effects of Hypericum perforatum and Quercetin in a Rat Model of Ischemia/Reperfusion Injury of Testes.

PURPOSE: This study aimed to compare the protective effects of Hypericum perforatum (Hp) and quercetin, a flavonoid, against ischemia/reperfusion (I/R) injury in rat testes. MATERIALS AND METHODS: This study included 28 male Wistar albino rats that were divided into four groups. Except for the sham group, torsion was created by rotating both testes at an angle of 720 degrees clockwise for 2 hours. The Hp and quercetin groups received 25 mg/kg Hp and quercetin intraperitoneally 30 minutes before detorsion, respectively. Orchiectomy was performed for the measurement of markers of oxidative stress and histopathological examination. RESULTS: In the Hp and quercetin groups, malondialdehyde (MDA) and nitric oxide (NO) levels and total oxidant capacity were significantly lower, the glutathione level and total antioxidant status were significantly higher, and Johnsen's testis biopsy scores were significantly higher than in the torsion/detorsion group (p ˂ 0.001). The markers of oxidative injury were significantly lower (p ˂ 0.001) and total antioxidant status was significantly higher (p ˂ 0.001), except for glutathione (p = 0.62) in the Hp group than in the quercetin group. Johnsen's score between Hp and quercetin groups was not significantly different (p = 0.80). CONCLUSION: Both Hp and quercetin have protective effects against I/R injury of the testes, but the protective effect of Hp was found to be stronger than that of quercetin.

Mesonephric adenocarcinoma of the uterine cervix: A case report and review of the literature.

Mesonephric adenocarcinoma is a rare neoplasm of uterine cervix. It originates from the mesonephric ductus remnant or mesonephric hyperplasia area. There have been few such cases reported. Our case was 64 years of age and her tumour held the whole endocervical wall. It was around 5cm in diameter, and had exophytic component as well. Bilateral pelvic and paraaortic lymph nodes were negative for metastasis.