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1.
Eur J Pharmacol ; 973: 176592, 2024 Jun 15.
Article En | MEDLINE | ID: mdl-38642666

Head and neck cancer (HNC) is the sixth most common malignancy worldwide. Although current modalities offer a wide variety of therapy choices, head and neck carcinoma has poor prognosis due to its diagnosis at later stages and development of resistance to current therapeutic tools. In the current study, we aimed at exploring the roles of miR-200c-3p during head and neck carcinogenesis and acquisition of taxol resistance. We analyzed miR-200c-3p levels in HNC clinical samples and cell lines using quantitative real-time polymerase chain reaction and evaluated the effects of differential miR-200c-3p expression on cancer-related cellular phenotypes using in-vitro tools. We identified and characterized a direct target of miR-200c-3p using in-silico tools, luciferase and various in-vitro assays. We investigated potential involvement of miR-200c-3p/SSFA2 axis in taxol resistance in-vitro. We found miR-200c-3p expression as significantly downregulated in both HNC tissues and cells compared to corresponding controls. Ectopic miR-200c-3p expression in HNC cells significantly inhibited cancer-related phenotypes such as viability, clonogenicity, migration, and invasion. We, then, identified SSFA2 as a direct target of miR-200c-3p and demonstrated that overexpression of SSFA2 induced malignant phenotypes in HNC cells. Furthermore, we found reduced miR-200c-3p expression in parallel with overexpression of SSFA2 in taxol resistant HNC cells compared to parental sensitive cells. Both involved in intracellular cytoskeleton remodeling, we found that SSFA2 works collaboratively with IP3R1 to modulate resistance to taxol in HNC cells. When considered collectively, our results showed that miR-200c-3p acts as a tumor suppressor microRNA and targets SSFA2/IP3R1 axis to sensitize HNC cells to taxol.


Drug Resistance, Neoplasm , Gene Expression Regulation, Neoplastic , Head and Neck Neoplasms , Inositol 1,4,5-Trisphosphate Receptors , MicroRNAs , Paclitaxel , Humans , Cell Line, Tumor , Cell Movement/drug effects , Down-Regulation/drug effects , Drug Resistance, Neoplasm/genetics , Gene Expression Regulation, Neoplastic/drug effects , Head and Neck Neoplasms/genetics , Head and Neck Neoplasms/drug therapy , Head and Neck Neoplasms/pathology , Head and Neck Neoplasms/metabolism , Inositol 1,4,5-Trisphosphate Receptors/genetics , Inositol 1,4,5-Trisphosphate Receptors/metabolism , MicroRNAs/genetics , MicroRNAs/metabolism , Paclitaxel/pharmacology
2.
Biomed Chromatogr ; 38(3): e5809, 2024 Mar.
Article En | MEDLINE | ID: mdl-38109869

Polygonum cognatum Meisn. (Polygonaceae) is used both as food and as a folk medicine to treat diabetes. This study aimed to evaluate the effect of the extracts, along with isolated compounds, from P. cognatum aerial parts on diabetes. In vitro studies were conducted using an α-glucosidase inhibitory assay, while in vivo antidiabetic studies were carried out on streptozotocin-induced diabetic rats. Effective extracts were subjected to isolation studies, and structures of the compounds were elucidated by spectroscopic methods. The ethyl acetate and n-butanol extracts had the highest effect in both in vitro and in vivo experiments. They also decreased aspartate transaminase, alanine transaminase and malondialdehyde levels, while increasing glutathione and superoxide dismutase activity in rats. From the active extracts, 11 phenolic compounds were isolated and characterized. Among the isolated compounds, quercetin was found to be the most active according to α-glucosidase inhibitory activity studies. This study provided scientific evidence for the traditional use of P. cognatum as a folk medicine for treating diabetes. The findings suggest that the ethyl acetate and n-butanol extracts, as well as quercetin, have the potential for development as antidiabetic agents.


Acetates , Diabetes Mellitus, Experimental , Polygonum , Rats , Animals , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/chemistry , Antioxidants/pharmacology , Polygonum/chemistry , Diabetes Mellitus, Experimental/drug therapy , Quercetin , 1-Butanol , alpha-Glucosidases , Plant Extracts/pharmacology , Plant Extracts/chemistry , Phytochemicals/pharmacology
3.
J Cell Biochem ; 124(10): 1628-1645, 2023 Oct.
Article En | MEDLINE | ID: mdl-37683055

Head and neck squamous cell carcinoma (HNSCC) is the sixth most common malignant cancer type worldwide. Although the therapeutic modalities currently used for patients with HNSCC improved in recent decades, HNSCC prognosis is still poor. Therefore, it is an urgent necessity to understand the pathogenesis of HNSCC, to develop novel and effective treatment strategies, and to characterize and identify the oncogenes that are responsible for an aggressive HNSCC phenotype. In this study, we aimed to better understand the roles of miR-1825 in the pathogenesis of HNSCC. We examined the impacts of miR-1825 deregulation on the cancer-associated phenotypes using in vitro tests evaluating cell viability, clonogenicity, cell migration, invasion, apoptosis, and stem cell characteristics. In addition, we investigated the effects of miR-1825 overexpression on the tumor formation capacity of head and neck cancer cells in vivo using nude mice. We searched for potential targets of miR-1825 using microarray analysis and luciferase assay. We found that miR-1825 expression is upregulated in head and neck cells and clinical tumor samples in comparison to corresponding controls, where it potentially acts as an oncogene. We, then, showed that ectopic miR-1825 overexpression promotes cellular phenotypes related to head and neck cancer progression in vitro and has a stimulating potential on cancer formation in vivo. We also identified FREM1 as a direct target of miR-1825 and demonstrated its reduced expression in HNSCC samples using immunohistochemistry analysis. Collectively, we suggest that the miR-1825/FREM1 axis serves as an important mediator of HNSCC development, where miR-1825 acts as an oncogene.

4.
Fitoterapia ; 170: 105658, 2023 Oct.
Article En | MEDLINE | ID: mdl-37648027

The medicinal plant Paeonia mascula L. is commonly used in Anatolian folk medicine for its antidiabetic properties. This study aimed to investigate the in vitro α-glucosidase enzyme inhibition effect, in vivo antidiabetic, and antioxidant activities of extracts obtained from P. mascula. The in vivo studies were conducted on diabetic rats induced with streptozotocin. The ethyl acetate and n-butanol extracts showed the highest efficacy in both in vitro and in vivo experiments, reducing AST, ALT, and MDA levels while increasing GSH and SOD activities in rats. In total, seven compounds were isolated from both extracts, and their structures were identified using spectroscopic methods such as 1D and 2D NMR and Mass Spectrometry. The in vitro α-glucosidase inhibition assay on purified compounds revealed that 1,2,3,4,6-penta-O-galloyl-ß-d-glucose was the most effective compound. These findings support the traditional use of P. mascula as an antidiabetic agent.

5.
Cell Biol Int ; 47(12): 1950-1963, 2023 Dec.
Article En | MEDLINE | ID: mdl-37641160

Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive neoplasms, which requires more effective prevention and treatment modalities. Previous studies found that protein O-fucosyltransferase 1 (POFUT1) upregulation promotes carcinogenesis, although the potential roles, underlying molecular mechanisms, and biological implications of POFUT1 in HNSCC were not investigated. In this study, in silico analyses referred POFUT1 as a potential oncogene in HNSCC. Further analysis of tumor and normal tissue samples as well as HNSCC cells with quantitative real-time polymerase chain reaction, Western blot analysis, and immunohistochemistry showed significant overexpression of POFUT1 in HNSCC clinical tumor tissue specimens and cell lines compared to corresponding controls. In vitro investigations revealed that overexpression of POFUT1 promoted phenotypes associated with cancer aggressiveness and its knockdown in HNSCC cells suppressed those phenotypes. Further xenograft experiments demonstrated that POFUT1 is an oncogene in vivo for HNSCC. Immunohistochemical analysis with human clinical samples and cancer cell-dorsal root ganglion ex-vivo coculture model showed that deregulation of POFUT1 is involved in the perineural invasion of HNSCC cells. These results suggest POFUT1 expression as a potential prognostic marker for patients with head and neck cancer and highlight its potential as a target for HNSCC therapy, although more molecular clues are needed to better define the functions of POFUT1 related to HNSCC carcinogenesis.


Carcinoma, Squamous Cell , Head and Neck Neoplasms , Humans , Squamous Cell Carcinoma of Head and Neck/genetics , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/pathology , Head and Neck Neoplasms/genetics , Phenotype , Carcinogenesis , Cell Line, Tumor , Cell Proliferation/genetics
6.
Front Pharmacol ; 14: 1161448, 2023.
Article En | MEDLINE | ID: mdl-37089925

Background: Acrylamide causes hepatotoxicity with the effect of oxidative stress and inflammatory processes. Carvacrol is a monoterpenic phenol with antioxidant and anti-inflammatory properties. Aims: To determine the effects of carvacrol on oxidative liver injury induced by acrylamide administration in rats. Methods: Rats were divided into three groups of six animals each: healthy group acrylamide group (ACR), and acrylamide + carvacrol group (TACR). First, carvacrol (50 mg/kg) was administered intraperitoneally to the CACR group. One hour later, acrylamide (20 mg/kg) was given orally to the ACR and CACR groups. This procedure was performed for 30 days, after which the animals were sacrificed. The malondialdehyde (MDA) and total glutathione (tGSH) levels, total oxidant (TOS) and total antioxidant status (TAS), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and nuclear factor kappa b (NF-κB) were measured in the excised liver tissues. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were determined in blood serum samples. Liver tissues were also examined histopathologically. Results: In the ACR group, malondialdehyde, TOS, ALT, AST levels, and NF-κB, IL-1ß, and TNF-α levels were found to be high, and tGSH and total antioxidant status levels were low. In addition, diffuse degenerative changes and necrosis in hepatocytes, and moderate inflammation in the portal region were detected in the liver tissues of the ACR group. While carvacrol prevented the biochemical changes induced by acrylamide, it also alleviated the damage in the histological structure. Conclusion: Carvacrol may be used for liver damage caused by acrylamide.

7.
An Acad Bras Cienc ; 95(2): e20201586, 2023.
Article En | MEDLINE | ID: mdl-37018835

The aim of this study is to investigate the effect of metyrosine on ischemia-reperfusion (I/R) induced ovarian injury in rats in terms of biochemistry and histopathology. Rats were divided into: ovarian I/R (OIR), ovarian I/R+50 mg/kg metyrosine (OIRM) and sham (SG) operations. OIRM group received 50 mg/kg metyrosine one hour before the application of the anesthetic agent, OIR and SG group rats received equal amount of distilled water to be used as a solvent orally through cannula. Following the application of the anesthetic agent, ovaries of OIRM and OIR group rats were subjected to ischemia and reperfusion, each of which took two hours. This biochemical experiment findings revealed high levels of malondialdehyde (MDA) and cyclo-oxygenase-2 (COX-2) and low levels of total glutathione (tGSH), superoxide dismutase (SOD) and cyclo-oxygenase-1 (COX-1) in the ovarian tissue of OIR group, with significant histopathological injury. In metyrosine group, MDA and COX-2 levels were lower than the OIR group whereas tGSH, SOD and COX-1 levels were higher, with slighter histopathological injury. Our experimental findings indicate that metyrosine inhibits oxidative and pro-inflammatory damage associated with ovarian I/R in rats. These findings suggest that metyrosine could be useful in the treatment of ovarian injury associated with I/R.


Ovary , Reperfusion Injury , Female , Rats , Animals , Ovary/metabolism , alpha-Methyltyrosine/metabolism , alpha-Methyltyrosine/pharmacology , Rats, Wistar , Cyclooxygenase 2/metabolism , Cyclooxygenase 2/pharmacology , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Ischemia/metabolism , Ischemia/pathology , Glutathione , Reperfusion , Superoxide Dismutase/metabolism , Oxidative Stress
9.
Oral Dis ; 29(3): 978-989, 2023 Apr.
Article En | MEDLINE | ID: mdl-34954855

OBJECTIVES: Diets and nutritional habits are critical during carcinogenic processes, where a diet poor in fruits and vegetables and rich in meat and other foods of animal origin facilitates carcinogenesis. In this study, we aimed at investigating the possible involvement of vitamin D deficiency (VDD) and high cholesterol (HC) together in oral squamous cell carcinoma (OSCC) through modulating glycolysis. SUBJECTS AND METHODS: We compared total cholesterol, LDL, HDL, triglycerides, LDH, and vitamin D levels of OSCC patients and control individuals. We used GEO datasets for gene set enrichment and 4-nitroquinoline-1-oxide induced in vivo oral carcinogenesis models to investigate contribution of VDD and HC during carcinogenesis via possible modulation of glycolysis. RESULTS: We found that VDD and HC co-exist in OSCC patients, and deregulation of cholesterol and vitamin D levels results in enrichment of genes related to glycolysis. We, then, demonstrated that VDD and HC on their own and together facilitated the formation of larger tumors in 4NQO-induced in vivo cancer models, which are suppressed by glycolysis inhibition. CONCLUSION: We reported collaborative contribution of HC and VDD during oral carcinogenesis, which is mainly carried out via altering energy metabolism in tumor cells.


Carcinoma, Squamous Cell , Head and Neck Neoplasms , Mouth Neoplasms , Vitamin D Deficiency , Rats , Animals , Carcinoma, Squamous Cell/chemically induced , Carcinoma, Squamous Cell/genetics , Carcinoma, Squamous Cell/metabolism , Mouth Neoplasms/genetics , Carcinogenesis/metabolism , Squamous Cell Carcinoma of Head and Neck , Vitamin D , Glycolysis , Vitamin D Deficiency/complications
10.
Ulus Travma Acil Cerrahi Derg ; 28(8): 1073-1081, 2022 Aug.
Article En | MEDLINE | ID: mdl-35920429

BACKGROUND: Acute cardiac contusion induced by trauma is known with its high mortality and morbidity. The role of oxidative stress and inflammation in its pathophysiology has led to the investigation of antioxidant and anti-inflammatory substances in non-sur-gical treatment. In this study, the effects of rutin which has these two features on acute cardiac contusion were investigated. METHODS: Thirty male albino Wistar rats were divided into three equal groups as healthy (HG), contusion (CG), and rutin + con-tusion (rutin + CG). A heart contusion was created dropping 200 g weight from 1-m height onto anterior thorax of CG (n=10) and Rutin + CG (n=10) group animals by anesthetizing with intraperitoneal administration of 60 mg/kg ketamine and xylazine inhalation at appropriate intervals. Thirty minutes after contusion was applied, rutin at the dose of 50 mg/kg was administered orally to the stomach by gavage to the rutin + CG group animals. The rutin was used once a day for 2 days. Rats were killed at the end of 48 h. Heart tissues were removed and examined biochemically and histopathologically. Troponin I (TP I) and creatine kinase-MB (CK-MB) were measured in blood samples taken from the tail veins just before the rats were killed. RESULTS: TP I, CK-MB, malondialdehyde, total oxidant status, and nuclear factor-kappa B levels increased in the CG when compared to the HG, and Rutin application prevented this increase, total glutathione (eGSH) and total antioxidant status levels decreased, and rutin application prevented this decrease. Histopathological findings also supported these findings. CONCLUSION: Rutin had a protective effect on heart tissue.


Contusions , Myocardial Contusions , Animals , Antioxidants/pharmacology , Contusions/drug therapy , Male , Oxidative Stress , Rats , Rats, Wistar , Rutin/pharmacology , Rutin/therapeutic use
11.
Adv Clin Exp Med ; 31(2): 129-137, 2022 Feb.
Article En | MEDLINE | ID: mdl-35156781

BACKGROUND: Cyclophosphamide is a drug used in various types of cancer. It can cause oxidative and inflammatory ovarian damage and infertility. Thiamine pyrophosphate (TPP) to be investigated for its effect on cyclophosphamide-induced ovarian damage and reproductive dysfunction in the present study is the active metabolite of thiamine. It has been shown that TPP protects organs and tissues from oxidative stress and proinflammatory cytokine damage. OBJECTIVES: To investigate the effect of TPP against the ovarian damage and reproductive dysfunction caused by cyclophosphamide in rats. MATERIAL AND METHODS: Albino Wistar type female rats were divided into healthy control (HG), cyclophosphamide (CYC) and TPP + cyclophosphamide (TPPC) groups (for each group, n = 12). Thiamine pyrophosphate at a dose of 25 mg/kg was injected intraperitoneally (ip.) in the TPPC group, and 0.9% NaCI solution was injected ip. in the CYC and HG groups. One hour after the injection, 75 mg/kg of cyclophosphamide was administered ip. in the TPPC and CYC groups. This procedure was repeated once a day for 30 days. At the end of this period, 6 rats from each group were euthanized with a high dose of anesthetic (50 mg/kg of sodium thiopental). Biochemical and histopathological examinations were performed on the extracted ovarian tissue. The remaining animals were kept in the laboratory with mature male rats for 2 months for reproduction. RESULTS: Thiamine pyrophosphate significantly decreased the cyclophosphamide-induced increase in the levels of the oxidant parameter malondialdehyde (MDA), proinflammatory nuclear factor kappa B (NF-κB), tumor necrosis factor alpha (TNF-α), and interleukin 1 beta (IL-1ß). In addition, TPP decreased the severe histopathological damage associated with cyclophosphamide in the ovarian tissue and prevented infertility. CONCLUSIONS: Our experimental results have suggested that TPP could be beneficial in the treatment of cyclophosphamide-induced ovarian injury and infertility.


Glutathione , Thiamine Pyrophosphate , Animals , Antioxidants/metabolism , Cyclophosphamide/toxicity , Female , Glutathione/metabolism , Male , Malondialdehyde/metabolism , Oxidative Stress , Rats , Rats, Wistar , Thiamine Pyrophosphate/pharmacology
12.
Interact Cardiovasc Thorac Surg ; 34(2): 245-249, 2022 01 18.
Article En | MEDLINE | ID: mdl-34587626

OBJECTIVES: This study investigated the efficacy and complications of albendazole use after surgery in patients with pulmonary hydatid cysts. METHODS: One hundred fifty-three consecutive patients who met the study criteria out of 215 patients who received prophylaxis with albendazole after surgery for isolated pulmonary hydatid cysts in our clinic between January 2011 and December 2020 were analysed retrospectively. RESULTS: Eighty-six out of 153 (56.2%) of cases were male and 67 (43.8%) were female. The average age was 24.6 ± 17.4 (between 3 and 71 years), 76 of them (49.7%) were 18 years old and younger, while 77 (50.3%) were adults. All cases were approached transthoracically and a total of 170 operations were performed on the 153 cases. Fever, weakness and dizziness were reported in only one patient who was given albendazole treatment. A partial increase in liver enzymes was observed in 16 cases (10.5%) after albendazole treatment. Mild leukopoenia and neutropenia were observed in only one of the cases. In 1 case, a second operation was performed 30 months later due to recurrence. Albendazole treatment was not required to be discontinued in any of the cases. Mortality was not observed in any of the cases. Factors such as mean age, cyst size and hospitalization period did not have a statistically significant effect on any changes in liver enzymes tests following albendazole therapy (P > 0.05). CONCLUSIONS: Albendazole treatment can safely be used for postoperative prophylaxis in patients with pulmonary hydatid cysts in a controlled manner without causing serious complications. SUBJ COLLECTION: 152.


Albendazole , Echinococcosis, Hepatic , Echinococcosis, Pulmonary , Adolescent , Adult , Aged , Albendazole/adverse effects , Child , Child, Preschool , Echinococcosis, Hepatic/complications , Echinococcosis, Hepatic/drug therapy , Echinococcosis, Hepatic/surgery , Echinococcosis, Pulmonary/complications , Echinococcosis, Pulmonary/surgery , Female , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
13.
Cell Oncol (Dordr) ; 45(1): 41-56, 2022 Feb.
Article En | MEDLINE | ID: mdl-34837170

PURPOSE: Development of chemoresistance is one of the major obstacles to the treatment of head and neck squamous cell carcinoma (HNSCC). The PI3K/Akt pathway, involved in drug resistance, has been found to be overactivated in > 90% of HNSCCs. Aberrant activation of the FGF receptors (FGFRs) has been reported to cause overactivation of the PI3K/Akt pathway and to be associated with the maintenance of stem cell features, which is controlled via SOX2 expression. In this study, we aimed at investigating the potential of using AZD4547, an orally bioavailable FGFR inhibitor, to overcome taxol-resistance by targeting the FGFR/Akt/SOX2 axis in HNSCC. METHODS: We initially evaluated FGFR2 and SOX2 expression using in silico tools. We analyzed the FGFR/Akt/SOX2 axis in normal/tumor tissue pairs and in recombinant FGF2 treated HNSCC cells. Next, we explored the effects of AZD4547 alone and in combination with taxol on the proliferation, migration and colony forming capacities of parental/taxol-resistant cells using in vitro models. RESULTS: We found that the p-FGFR, p-AKT, p-GSK-3ß and SOX2 expression levels were higher in tumor tissues than in its corresponding normal tissues, and that AZD4547 effectively suppressed the expression of FGFR and its downstream targets in recombinant FGF2 treated HNSCC cells. We also found that AZD4547 diminished the viability, migration and colony forming capacity of HNSCC cells, and that co-treatment with taxol potentiated the impact of taxol on these cells. Finally, we found that AZD4547 inhibited the overexpressed FGFR/Akt/SOX2 axis and profoundly suppressed cancer-related phenotypes in taxol-resistant HNSCC cells. CONCLUSION: From our data we conclude that AZD4547 may increase the impact of taxol during HNSCC treatment. We suggest AZD4547 as a therapeutic agent to overcome taxol-resistance.


Drug Resistance, Neoplasm , Head and Neck Neoplasms , Proto-Oncogene Proteins c-akt , Benzamides/pharmacology , Cell Line, Tumor , Cell Proliferation , Glycogen Synthase Kinase 3 beta/metabolism , Head and Neck Neoplasms/drug therapy , Humans , Paclitaxel/pharmacology , Phosphatidylinositol 3-Kinases/metabolism , Piperazines/pharmacology , Proto-Oncogene Proteins c-akt/metabolism , Pyrazoles/pharmacology , Receptors, Fibroblast Growth Factor/metabolism , SOXB1 Transcription Factors/metabolism
14.
Acta Cir Bras ; 36(10): e361005, 2021.
Article En | MEDLINE | ID: mdl-34817026

PURPOSE: Reactive oxygen species (ROS), interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) have been shown in the pathogenesis of acrylamide neurotoxicity. Hippophae rhamnoides L. extract (HRE) has a cytoprotective effect by stabilizing the production of ROS, IL-1ß and TNF-α. The objective of the article was to investigate the effect of HRE on acrylamide-induced brain damage in rats biochemically and histopathologically. METHODS: To the HRE+acrylamide only (ACR) group (n=6) of the animals, HRE was administered orally at a dose of 50 mg / kg into the stomach by gavage. The same volume of solvent (olive oil) was administered orally to the ACR (n=6) and healthy (HG) (n=6) groups. One hour after HRE administration, acrylamide was given orally at a dose of 20 mg/kg to HRE+ACR and ACR groups in the same way. This procedure was repeated once a day for 30 days. At the end of this period, brain tissues extracted from animals killed with 50 mg/kg thiopental anesthesia were examined biochemically and histopathologically. RESULTS: It has been shown that HRE prevents the increase of malondialdehyde (MDA), myeloperoxidase (MPO), IL-1ß and TNF-α with acrylamide and the decrease of total glutathione (tGSH) and glutathione reductase (GSHRd) levels in brain tissue. CONCLUSIONS: HRE may be useful in the treatment of acrylamide-induced neurotoxicity.


Brain Injuries , Hippophae , Plant Extracts/pharmacology , Animals , Antioxidants/pharmacology , Brain Injuries/chemically induced , Brain Injuries/drug therapy , Hippophae/chemistry , Malondialdehyde , Oxidative Stress , Rats
15.
Asian Pac J Cancer Prev ; 22(8): 2429-2435, 2021 Aug 01.
Article En | MEDLINE | ID: mdl-34452555

OBJECTIVE: The aim of this project is to identify the differences in expression levels of stem cell related genes (SCRGs) in normal colon tissue, histopathologically staged colon polyps and colon cancer, and to explain the role of SCRGs in the formation of CC and for contributing the practical usage of SCRGs in the diagnosis and treatment of CC. METHODS: Normal colon tissue, hyperplastic polyps, histopathologically (HGD and LGD) staged tubular, tubulovillous and villous polyps and colon cancer paraffin tissue (FFPE) samples were used. Transcription factor genes (OCT4, KLF4, SOX2, MYC, NANOG, and REX1) and cell surface markers (CD133, LGR5), which are associated with embryonic stem cells, induced pluripotent stem cells, and cancer stem cells, have been selected for measuring expression levels from the selected tissues. After isolation of total RNA from FFPE tissues, SCRGs expressions were measured by RT-qPCR method. RESULTS: SCRGs expression differences were detected in normal-adenoma-cancer progression. A significant increase was observed in the expression of LGR5 (p: 0.01) and PROM1 (p: 0.005) genes in villous HGD polyps, LGR5 (p: 0.003) gene in G1, and LGR5 (p: 0.0002) and MYC (p: 0.002) genes in G2 stage tumor tissues. When compared with each other, a significant increase in SCRGs expression is noticeable in the formation from adenoma to cancer tissues regarding malign phenotype. CONCLUSION: This study shows that the increase of SCRGs expressions occurs with high-grade dysplasia (HGD), villous features, and the malignant phenotype. Increased expression levels of LGR5, PROM1, KLF4, SOX2, and MYC in HGD and cancerous tissues support the malignant phenotype and the existence of cancer stem cells and demonstrate that they can be used to assess diagnosis and prognosis. Identification of tissue-specific SCRGs expressions will help design new therapies to control the development and progression of colonic neoplasia.


Adenoma/pathology , Biomarkers, Tumor/genetics , Carcinogenesis/pathology , Colonic Polyps/pathology , Colorectal Neoplasms/pathology , Hyperplasia/pathology , Neoplastic Stem Cells/pathology , Adenoma/metabolism , Carcinogenesis/metabolism , Colonic Polyps/metabolism , Colorectal Neoplasms/genetics , Colorectal Neoplasms/metabolism , Disease Progression , Female , Follow-Up Studies , Humans , Hyperplasia/metabolism , Male , Middle Aged , Neoplastic Stem Cells/metabolism , Phenotype , Prognosis
16.
Turk Patoloji Derg ; 37(2): 93-105, 2021.
Article En | MEDLINE | ID: mdl-33973640

Aziz Sancar, Nobel Prize winning Turkish scientist, made several discoveries which had a major impact on molecular sciences, particularly disciplines that focus on carcinogenesis and cancer treatment, including molecular pathology. Cloning the photolyase gene, which was the initial step of his work on DNA repair mechanisms, discovery of the "Maxicell" method, explanation of the mechanism of nucleotide excision repair and transcription-coupled repair, discovery of "molecular matchmakers", and mapping human excision repair genes at single nucleotide resolution constitute his major research topics. Moreover, Sancar discovered the cryptochromes, the clock genes in humans, in 1998, and this discovery led to substantial progress in the understanding of the circadian clock and the introduction of the concept of "chrono-chemoterapy" for more effective therapy in cancer patients. This review focuses on Aziz Sancar's scientific studies and their reflections on molecular pathology of neoplastic diseases. While providing a new perspective for researchers working in the field of pathology and molecular pathology, this review is also an evidence of how basic sciences and clinical sciences complete each other.


Biomedical Research/history , Neoplasms/history , Nobel Prize , Pathology, Molecular/history , Cloning, Molecular , Cryptochromes/genetics , Cryptochromes/metabolism , DNA Repair , Deoxyribodipyrimidine Photo-Lyase/genetics , Deoxyribodipyrimidine Photo-Lyase/metabolism , Gene Expression Regulation, Neoplastic , History, 20th Century , History, 21st Century , Humans , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/pathology
17.
Eurasian J Med ; 53(3): 214-219, 2021 Oct.
Article En | MEDLINE | ID: mdl-35110099

OBJECTIVE: In this study, we aimed to compare the results of patients who underwent surgery by thoracotomy and Video-assisted thoracoscopic surgery (VATS) in mediastinal neurogenic tumors. MATERIALS AND METHODS: Twenty-six consecutive cases (12 males and 14 females; mean age 39.4 ± 22.3 years; range 1-72 years) who were histopathologically diagnosed as having mediastinal neurogenic tumors between January 2000 and August 2020 were included in a single-center, retrospective study. RESULTS: There were 5 (19.2%) children and 21 (80.8%) adults. Lesions in all cases were located in the posterior mediastinum. Schwannoma was detected histopathologically in 18 cases (69.2%), and all of these cases were adult patients. Resection was performed by thoracotomy in 14 cases (7 right and 7 left) and 12 cases by thoracoscopy (7 right and 5 left). The mean tumor size was 7.4 ± 1.9 cm (range 5-12 cm) in the thoracotomy group and 4.3 ± 1.9 cm (range 2-7 cm) in the VATS group (P = .001). Mean operative time was 101.7 ± 27.8 min (range 70-150 min) in the thoracotomy group and 77.9 ± 24.3 min (range 60-150 min) in the VATS group (P = .014). Mean postoperative hospital stay was 7.4 ± 4.0 days (range 3-20 days) in the thoracotomy group and 4.7 ± 1.7 days (range 2-7 days) in the VATS group (P = .040). CONCLUSION: Most of the mediastinal neurogenic tumors are benign and surgical resection is required in their treatment. With increasing experience, resection can be performed thoracoscopically in most cases.

18.
Acta cir. bras ; 36(10): e361005, 2021. graf
Article En | LILACS, VETINDEX | ID: biblio-1349864

ABSTRACT Purpose: Reactive oxygen species (ROS), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) have been shown in the pathogenesis of acrylamide neurotoxicity. Hippophae rhamnoides L. extract (HRE) has a cytoprotective effect by stabilizing the production of ROS, IL-1β and TNF-α. The objective of the article was to investigate the effect of HRE on acrylamide-induced brain damage in rats biochemically and histopathologically. Methods: To the HRE+acrylamide only (ACR) group (n=6) of the animals, HRE was administered orally at a dose of 50 mg / kg into the stomach by gavage. The same volume of solvent (olive oil) was administered orally to the ACR (n=6) and healthy (HG) (n=6) groups. One hour after HRE administration, acrylamide was given orally at a dose of 20 mg/kg to HRE+ACR and ACR groups in the same way. This procedure was repeated once a day for 30 days. At the end of this period, brain tissues extracted from animals killed with 50 mg/kg thiopental anesthesia were examined biochemically and histopathologically. Results: It has been shown that HRE prevents the increase of malondialdehyde (MDA), myeloperoxidase (MPO), IL-1β and TNF-α with acrylamide and the decrease of total glutathione (tGSH) and glutathione reductase (GSHRd) levels in brain tissue. Conclusions: HRE may be useful in the treatment of acrylamide-induced neurotoxicity.


Animals , Rats , Brain Injuries/chemically induced , Brain Injuries/drug therapy , Plant Extracts/pharmacology , Hippophae/chemistry , Oxidative Stress , Malondialdehyde , Antioxidants/pharmacology
19.
J Lab Physicians ; 12(1): 32-37, 2020 Mar.
Article En | MEDLINE | ID: mdl-32792791

Objective The aim of our study was to evaluate the effect of two different doses of lycopene, an antioxidant, on experimentally induced ovarian ischemia/reperfusion (IR) injury in rat model. Materials and Methods Twenty-four female rats were randomly divided into four groups: sham operation (group 1), 3-hour ischemia, 3-hour reperfusion (IR) (group 2), and IR + 100 mg/kg lycopene (PO) (group 3), IR + 200 mg/kg of lycopene (group 4). The rats' superoxide dismutase (SOD), myeloperoxidase (MPO) activities, malondialdehyde (MDA), and glutathione (GSH) levels were calculated. Ovarian tissue damage was assessed using a histopathological scoring system. Results Serum parameter levels and histological scores showed that treatment with lycopene may be conservative approach to prevent IR injury after the ovarian detorsion procedure.The improvement with lycopene was higher at 200 mg than at 100 mg. The MPO and MDA values were significantly lower in groups 3 and 4 as compared with group 2 ( p < 0.05), whereas the MPO and MDA values were lower in group 4 as compared with group 3.The SOD and GSH values were significantly higher in groups 3 and 4 as compared with group 2 ( p < 0.05), whereas the SOD and GSH values were higher in group 4 as compared with group 3.Tissue damage scores were elevated in the IR group compared with the sham group, but the treatment with different lycopene doses after reperfusion improved the histopathological tissue damage scores. Conclusion The results showed that lycopene treatment reduced ovarian IR damage. Antioxidant activity was found to increase in a dose-dependent manner. Lycopene treatment may be conservative approach for ovarian torsion patients after the detorsion procedure to prevent IR damage.

20.
Diagn Cytopathol ; 48(12): 1211-1216, 2020 Dec.
Article En | MEDLINE | ID: mdl-32621655

BACKGROUND: Multinucleated giant cell (MGC) present in a variety of non-neoplastic and neoplastic lesions of the thyroid on cytology samples. We aimed to investigate whether certain MGC features that can help us in routine cytopathology practice. METHOD: One hundred and thirty seven cases thyroid fine-needle aspiration material, which was diagnosed as indeterminate or malignant according to the Bethesda categorization, were reviewed. All cytomorphological features of the MGCs were documented. These features correlated with Bethesda categories and the final diagnosis of the subsequent surgical specimen. RESULTS: The presence of the MGCs was identified in 42% of the samples (58 cases-total 236 MGCs). Eighty eight of them (37%) had dense cytoplasm, 148 of them had foamy cytoplasm. The mean number of dense and foamy MGC per case was higher in the malignant category (3.2 for dense MGC and 6 for foamy MGC per case). All dense MGCs were found to be in patients with papillary thyroid carcinoma (PTC). Remarkably, follicular patterned lesions had less often dense MGC compared to papillary patterned lesions (16.6% and 46.8% respectively). We detected a nuclear irregularity in 49 dense MGC (55%), groove-like features in 24 dense MGC (27.2%), and presence of some material/cell in 8 dense MGC (9%). CONCLUSION: The presence of dense MGC is an important finding for guiding accurate Bethesda categorization, especially in indeterminate and malignant categories. Besides, the presence of some material or cell in MGCs cytoplasm can be an important indicator for the prognosis of the PTC cases.


Giant Cells/pathology , Thyroid Gland/pathology , Thyroid Neoplasms/pathology , Adult , Aged , Biopsy, Fine-Needle/methods , Cell Nucleus/pathology , Cytoplasm/pathology , Female , Humans , Male , Middle Aged , Prognosis , Thyroid Cancer, Papillary/pathology , Young Adult
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