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1.
Int J Gynecol Cancer ; 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38950923

RESUMO

OBJECTIVE: To investigate the impact of cumulative cisplatin dose on clinical outcomes in locally advanced cervical cancer patients undergoing definitive chemoradiotherapy. METHODS: A retrospective analysis was conducted on 654 patients with stage IB3-IVA disease treated with definitive chemoradiotherapy. Radiotherapy was applied as external beam pelvic with or without para-aortic radiotherapy and brachytherapy. Concomitant chemotherapy was in the form of weekly or 3 weekly cisplatin. Data on demographics, treatment protocols, cumulative cisplatin dose, adverse effects, and survival outcomes were collected. Statistical analyses, including univariate and multivariate Cox regression models, were used to assess factors influencing progression free survival and overall survival. RESULTS: The median cumulative cisplatin dose was 210 mg (range 40-320), and ≥200 mg in 503 (76.9%) patients. Median follow-up was 35 months (range 1-150). The 5 year progression free survival and overall survival rates were 66.9% and 77.1%, respectively. Multivariate analysis identified poor performance status, non-squamous cell histology, presence of lymph node metastases, and hemoglobin <10 g/dL before chemoradiotherapy as poor prognostic factors for both progression free survival and overall survival in the whole group. When stage III cases were evaluated separately, the cumulative cisplatin dose <200 mg was found to be a significant poor prognostic factor in overall survival (hazard ratio 1.79, 95% confidence interval 1.1 to 3.0, p=0.031). CONCLUSION: Our study showed that a cumulative cisplatin dose >200 mg, particularly in patients with lymph node metastases, significantly improved overall survival. Factors such as anemia, toxicity related challenges, and comorbidities were identified as critical considerations in treatment planning. These findings emphasize the balance between maximizing therapeutic efficacy and managing toxicity, guiding personalized treatment approaches for locally advanced cervical cancer.

2.
Oncology ; 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-39008971

RESUMO

INTRODUCTION: Our study delves into the intricate interplay of risk factors and the strategic selection of adjuvant therapy, scrutinizing their influence on recurrence and survival outcomes in stage IIA (T3N0M0) colon cancer patients. MATERIALS AND METHODS: The study examined the medical records of patients who underwent surgery for stage IIA colon cancer. Identification of stage IIA (pT3N0M0) colon cancer involved a comprehensive review of postoperative clinical records and histological reports. Parameters such as demographic data, tumor characteristics, MSI status, tumor locations, recurrence risk factors, preoperative CEA levels, and adjuvant treatments were systematically evaluated. RESULTS: In our study involving 220 patients, 138 were male (62.7%), with a median age of 62 years and a median body mass index (BMI) of 25.1 kg/m². In the patient group without risk factors, no statistically significant difference was detected in DFS rates between those who received treatment and those who did not (p=0.546). DFS rates of patients with >1 risk factor were found to be statistically significantly lower than those with a single risk factor (p=0.017). In patients with >1 risk factor, the DFS of those who did not receive adjuvant treatment was significantly lower than those who received adjuvant treatment (p<0.001). In the patient group with recurrence, when adjuvant treatments were considered, recurrence was observed to be significantly higher in the group receiving capecitabine (p=0.01). CONCLUSION: The decision for adjuvant chemotherapy in stage IIA colon cancer patients involves careful consideration of various parameters and risk factors. The evolving landscape of research may refine recommendations, ensuring optimal treatment outcomes while minimizing unnecessary toxicity.

3.
Ann Diagn Pathol ; 70: 152301, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38581761

RESUMO

INTRODUCTION: Despite screening, the incidence of breast cancer is increasing worldwide. Neoadjuvant chemotherapy (NAC) response is one of the most important parameters taken into consideration in surgery, optimal adjuvant chemotherapy planning and prognosis prediction. Research on predictive markers for the response to NAC is still ongoing. In our study, we investigated the relationship between tumor-infiltrating neutrophils/mast cells/lymphocytes and NAC response in breast carcinomas. MATERIAL AND METHOD: Study included 117 patients who were diagnosed with invasive breast carcinoma using core needle biopsy. In these biopsies tumor-infiltrating neutrophils/mast cells/lymphocytes were evaluated and Miller Payne Score was used for NAC response. RESULT: 53 patients exhibited high TILs, 36 had high TINs, and 46 showed high TIMs. While pathological complete response was 27 % in all patients, it was 38 % in high TINs patients, 35 % in high TILs patients, and 28 % in high TIMs patients. High TIMs were observed to be statistically associated with survival. TILs, TINs, nuclear grade, ER, PR and HER2 expression, Ki-67 proliferation index were found to be associated with the Miller - Payne score. In multivariate analysis, TINs, nuclear grade, pathological stage, and molecular subtype were found to be independent risk factors for treatment response. CONCLUSION: TINs have better prognostic value to predict neoadjuvant treatment than TILs. High TIMs are associated with increased overall survival. The inclusion of TINs in NAC response and TIMs in overall survival in pathology reports and treatment planning is promising in breast carcinomas as they are simple to use and reproducible markers.


Assuntos
Neoplasias da Mama , Linfócitos do Interstício Tumoral , Terapia Neoadjuvante , Neutrófilos , Humanos , Neoplasias da Mama/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/imunologia , Feminino , Terapia Neoadjuvante/métodos , Pessoa de Meia-Idade , Adulto , Linfócitos do Interstício Tumoral/imunologia , Neutrófilos/patologia , Neutrófilos/metabolismo , Idoso , Prognóstico , Quimioterapia Adjuvante/métodos , Linfócitos/patologia , Linfócitos/metabolismo
4.
Biomed Mater ; 19(2)2024 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-38194706

RESUMO

Type 1 diabetes-mellitus (T1DM) is characterized by damage of beta cells in pancreatic islets. Cell-sheet engineering, one of the newest therapeutic approaches, has also been used to create functional islet systems by creating islet/beta cell-sheets and transferring these systems to areas that require minimally invasive intervention, such as extrahepatic areas. Since islets, beta cells, and pancreas transplants are allogeneic, immune problems such as tissue rejection occur after treatment, and patients become insulin dependent again. In this study, we aimed to design the most suitable cell-sheet treatment method and macrocapsule-device that could provide long-term normoglycemia in rats. Firstly, mesenchymal stem cells (MSCs) and beta cells were co-cultured in a temperature-responsive culture dish to obtain a cell-sheet and then the cell-sheets macroencapsulated using different concentrations of alginate. The mechanical properties and pore sizes of the macrocapsule-device were characterized. The viability and activity of cell-sheets in the macrocapsule were evaluatedin vitroandin vivo. Fasting blood glucose levels, body weight, and serum insulin & C-peptide levels were evaluated after transplantation in diabetic-rats. After the transplantation, the blood glucose level at 225 mg dl-1on the 10th day dropped to 168 mg dl-1on the 15th day, and remained at the normoglycemic level for 210 days. In this study, an alginate macrocapsule-device was successfully developed to protect cell-sheets from immune attacks after transplantation. The results of our study provide the basis for future animal and human studies in which this method can be used to provide long-term cellular therapy in T1DM patients.


Assuntos
Diabetes Mellitus Tipo 1 , Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Ratos , Humanos , Animais , Diabetes Mellitus Tipo 1/terapia , Transplante das Ilhotas Pancreáticas/métodos , Glicemia/metabolismo , Alginatos , Insulina/metabolismo
5.
Clin Nucl Med ; 49(2): e68-e69, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38170920

RESUMO

ABSTRACT: Medication-related osteonecrosis of the jaw (ONJ) is rare adverse effect of zoledronic acid. We present ONJ detected in a 65-year-old man with prostate cancer who underwent 18 F-FDG PET/CT for metabolic characterization and to exclude a second primary malignancy of the liver lesion observed in 68 Ga-PSMA PET/CT. ONJ has high metabolic activity on 18 F-FDG PET/CT and no PSMA receptor activation on the 68 Ga-PSMA PET/CT. In this case, we wanted to underline the importance of 18 F-FDG PET/CT imaging of medication-related ONJ in patients receiving zoledronic acid therapy and to emphasize that rapid and appropriate treatment can be provided.


Assuntos
Osteonecrose , Neoplasias da Próstata , Masculino , Humanos , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Fluordesoxiglucose F18 , Ácido Zoledrônico , Compostos Radiofarmacêuticos , Radioisótopos de Gálio , Neoplasias da Próstata/complicações , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/patologia
6.
Med Princ Pract ; 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38091965

RESUMO

OBJECTIVE: In studies conducted on non-small cell lung cancer (NSCLC) patients, many factors such as age, stage, weight loss, lymph node, and pleural involvement have been shown to affect survival. On the other hand, systemic inflammation plays a critical role in proliferation, migration, invasion, and metastasis. Inflammation and nutrition-based prognostic scores are reported to be associated with survival in patients with NSCLC. The aim of our study is to show the effects of these scores on survival and disease progression in NSCLC patients. SUBJECTS AND METHODS: Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), modified Glasgow prognostic score (mGPS), and prognostic nutritional index (PNI) values in 102 patients with stage 1,2 and 3A NSCLC were analyzed retrospectively. RESULTS: NLR (p < 0.001), PLR (p = 0.001), PNI (p < 0.001), and mGPS (p = 0.001) variables showed a statistically significant difference according to mortality groups. NLR and PLR values were higher in exitus patients. However, PNI values were higher in surviving patients. NLR (p < 0.001), PLR (p = 0.004), PNI (p = 0.001), and mGPS (p = 0.015) variables showed a statistically significant difference in terms of locoregional recurrence. PNI (p = 0.001) and mGPS (p = 0.001) in terms of distant metastasis development during follow-up and treatment, showed a statistically significant difference. CONCLUSION: NLR, PLR, PNI, and mGPS are easily accessible and non-invasive parameters and provide predictive information about survival and disease course. We showed the effect of these parameters on the prognosis.

7.
Med Oncol ; 40(12): 359, 2023 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-37966661

RESUMO

Lung cancer continues to be a major health problem worldwide owing to its incidence, and causes physical, psychological, social, and economic problems. Activated cytotoxic T cells (ACTC) are positively correlated with the tumor microenvironment (TME), improving the prognosis of cancer patients. Recently, ACTC-derived exosomes (ACTC-dExo) were implicated in this effect by inhibiting mesenchymal stem cells, which may promote metastasis in the TME. Exosomes are thought to be advantageous for the specific delivery of drugs to cancer cells because they have the characteristics of natural liposomes, are nanosized, and remain largely stable in the blood due to the protein and lipid content they carry on their membranes. In this study, we aimed to determine the cytotoxic and metastatic inhibitory effects of ACTC-dExo in A549 cells in vitro. Cytotoxic CD8+ T cells were isolated from whole blood obtained from healthy individuals and cultured for 5-7 days after stimulation. The ACTC-dExo serum-free culture medium was collected by ultracentrifugation. Characterization and quantification of the isolated exosomes were performed using flow cytometry, electron microscopy, zeta-sizer measurements, and bicinchoninic acid (BCA) assays. We co-cultured ACTC and ACTC-dExo with A549 cells for 48 h. The viability of A549 cells was evaluated using a WST-1 assay. The metastasis-related genes MMP2, MMP9, TWIST, SNAI1, and CDH1 were detected by qRT-PCR, and MMP2 and MMP9 proteins were evaluated by confocal microscopy. In addition, changes in cell migration were investigated using a scratch assay. ACTC-dExo were found to have anti-proliferative and anti-metastatic effects and reduced cancer cell proliferation and metastatic properties.


Assuntos
Antineoplásicos , Exossomos , Neoplasias Pulmonares , Humanos , Linfócitos T CD8-Positivos , Metaloproteinase 2 da Matriz , Metaloproteinase 9 da Matriz , Microambiente Tumoral
8.
Tissue Cell ; 84: 102195, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37573608

RESUMO

OBJECTIVE: Decellularization is the process to obtain natural scaffolds with tissue integrity and extracellular matrix components, and recellularization is used to produce tissue-like constructs with specific cell types. In this study, rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) were cultured on decellularized heart extracellular matrix. These cells were then induced to differentiate into cardiomyogenic cells under the stimulatory effect of vascular endothelial growth factor (VEGF) and other chemicals. This study aimed to investigate the effect of the cardiac extracellular matrix and VEGF on cardiomyogenic differentiation in the context of the Notch and Hedgehog signaling pathways. METHODS: Heart samples extracted from rats were decellularized by serial application of detergent to remove cells from the tissue, and then recellularized with rBM-MSCs. The recellularized tissue matrices were then analyzed for cardiomyogenesis. Cardiomyogenic differentiation was performed on decellularized heart extracellular matrix (ECM; three-dimensional scaffolds) and culture plates (two-dimensional cell culture system) for 28 days to understand the effects of the heart extracellular matrix. In addition, differentiation was induced with and without the stimulatory effect of VEGF to understand the effect of VEGF on cardiomyogenic differentiation of rBM-MSCs. RESULTS: Immunofluorescence staining showed that decellularization of the heart was performed effectively and successfully. After decellularization process, the heart extracellular matrix was completely free of cells. It was observed that rBM-MSCs transplanted onto the heart extracellular matrix remained viable and proliferated for 21 days after recellularization. The rBM-MSCs promoted cardiomyogenic differentiation in the conventional differentiation medium but were inversely affected by both VEGF and heart extracellular matrix proteins. Lower expression of connexin43 and cardiac troponin I genes was observed in cells induced by either matrix proteins or VEGF, compared to cells differentiated by chemical agents alone. CONCLUSION: In this study, we investigated the effect of decellularized heart extracellular matrix and VEGF on cardiomyogenic differentiation of rBM-MSCs. On the decellularized cardiac extracellular matrix, rBM-MSCs maintained their viability by adhering to the matrix and proliferating further. The adhesion of the cells to the matrix also produced a physical stimulus that led to the formation of histological structures resembling myocardial layers. Chemical stimulation of the decellularized heart extracellular matrix and cardiomyogenic differentiation supplements resulted in increased expression of cardiomyogenic biomarkers through modulation of the Notch and Hedgehog signaling pathways.


Assuntos
Células-Tronco Mesenquimais , Alicerces Teciduais , Ratos , Animais , Alicerces Teciduais/química , Fator A de Crescimento do Endotélio Vascular/metabolismo , Proteínas Hedgehog/análise , Proteínas Hedgehog/metabolismo , Proteínas Hedgehog/farmacologia , Diferenciação Celular , Matriz Extracelular/metabolismo
9.
Tissue Cell ; 82: 102110, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37235912

RESUMO

OBJECTIVE: In this study, it was aimed to provide a therapeutic approach for T1DM by encapsulating the pancreatic islets with mesenchymal stem cells and decellularized pancreatic extracellular matrix to support the survival of islets while maintaining their cellular activity. METHOD: Pancreatic extracellular matrix was decellularized using different concentrations of detergent series. After the preparation of the protein-based tissue extracellular matrix was shown to be free of cells or any genetic material by molecular, immunofluorescence and histochemical techniques. Following the homogenization of the decellularized pancreatic extracellular matrix and the analysis of its protein composition by LC-MS, the matrix proteins were incorporated with pancreatic islets and rat adipose tissue-derived MSCs (rAT-MSCs) in alginate microcapsules. Glucose-stimulated insulin secretion property of the islet cells in the microbeads was evaluated by insulin ELISA. The gene expression profile of the encapsulated cells was analyzed by Real-Time PCR. RESULTS: Unlike the protein composition of whole pancreatic tissue, the decellularized pancreas matrix was free of histone proteins or proteins originated from mitochondria. The protein matrix derived from pancreatic tissue was shown to support the growth and maintenance of the islet cells. When compared to the non-encapsulated pancreatic islet, the encapsulated cells demonstrate to be more efficient in terms of insulin expression. CONCLUSION: The extracellular pancreatic matrix obtained in this study was directly used as supplementary in the alginate-based microcapsule enhancing the cell survival. The tissue matrix protein and alginate had a synergistic effect on total insulin secretion, which might have the potential to overcome the insulin deficiency. Despite the improvement in the cell viability and the number, the efficiency of the insulin secretion in response to glucose stimulation from the alginate microcapsules did not meet the expectation when compared with the non-encapsulated pancreatic islets.


Assuntos
Transplante das Ilhotas Pancreáticas , Ilhotas Pancreáticas , Células-Tronco Mesenquimais , Ratos , Animais , Cápsulas/metabolismo , Cápsulas/farmacologia , Insulina/metabolismo , Glucose/farmacologia , Glucose/metabolismo , Células-Tronco Mesenquimais/metabolismo , Alginatos/química
10.
Exp Eye Res ; 229: 109431, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36870440

RESUMO

PURPOSE: To investigate the efficacy of nintedanib on preventing postoperative scar in formation following glaucoma filtering surgery (GFC) in rabbits in comparison with Mitomycin-C (MMC). DESIGN: Experimental Animal Study. METHODS: 24 New Zealand rabbits were divided randomly into 3 groups as Sham, Nindetanib and MMC(n = 8). Limbal-based trabeculectomy was performed on the right eyes of the rabbits. Left eyes that did'nt undergo surgery were included in the control group (n = 8). Following surgery, Intraocular pressures (IOP), postoperative complications and morphological changes in the bleb were evaluated. On the 28th day, eight eyes from each group were enucleated and histologically and immunohistochemically analyzed. Matrix metalloproteinase-2 (MMP-2), Transforming Growth Factor-1 (TGF-B1) and alpha-smooth muscle actin (a-SMA) were evaluated. RESULTS: It was observed that nintedanib has no side effects and reduces subconjunctival fibrosis. Postoperative IOP values in the Nindetanib group were lower than the other groups (p < 0.05). The longest bleb survival was observed in the Nintedanib group and the shortest in the Sham group (p < 0.001). Conjunctival vascularity and inflammation was reduced in the Nintedanib group compared to the Sham group (p < 0.05). The highest subconjunctival fibrosis was observed in the Sham group and the least in the Nintedanib group (p < 0.05). Although the fibrosis score was found lower in the Nintedanib group compared to the MMC(p > 0.05). α-SMA TGF-ß1, MMP-2 expressions were similar in Nintedanib and MMC groups (p > 0.05), however, it was observed that significantly decreased in both groups compared to Sham group (p < 0.05). CONCLUSION: It has been observed that Nindetanib suppress fibroblast proliferation Thus, It may be a drug that can prevent subconjunctival fibrosis in GFC.


Assuntos
Cirurgia Filtrante , Glaucoma , Trabeculectomia , Animais , Coelhos , Cicatriz/etiologia , Cicatriz/prevenção & controle , Cicatriz/patologia , Túnica Conjuntiva/metabolismo , Fibrose , Glaucoma/metabolismo , Pressão Intraocular , Metaloproteinase 2 da Matriz/metabolismo , Mitomicina/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Tirosina/metabolismo
11.
Diagnostics (Basel) ; 13(4)2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36832228

RESUMO

The thyroid nodule risk stratification guidelines used in the literature are based on certain well-known sonographic features of nodules and are still subjective since the application of these characteristics strictly depends on the reading physician. These guidelines classify nodules according to the sub-features of limited sonographic signs. This study aims to overcome these limitations by examining the relationships of a wide range of ultrasound (US) signs in the differential diagnosis of nodules by using artificial intelligence methods. An innovative method based on training Adaptive-Network Based Fuzzy Inference Systems (ANFIS) by using Genetic Algorithm (GA) is used to differentiate malignant from benign thyroid nodules. The comparison of the results from the proposed method to the results from the commonly used derivative-based algorithms and Deep Neural Network (DNN) methods yielded that the proposed method is more successful in differentiating malignant from benign thyroid nodules. Furthermore, a novel computer aided diagnosis (CAD) based risk stratification system for the thyroid nodule's US classification that is not present in the literature is proposed.

12.
Mol Cell Probes ; 66: 101861, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36162595

RESUMO

Cisplatin is one of the metal containing drugs for the solid cancer treatments. However, its side-effects limit its application in the cancer treatment. Stem cell therapy is a promising treatment for the tissue damage caused by the chemotherapeutic agents, like cisplatin. Exosomes secreted by mesenchymal stem cells (MSCs) could be used for cell-free regenerative treatment, but their potency and reproducibility are questionable. In this study, the microenvironment of the renal tubular epithelial cells was mimicked by coculture of endothelial-, renal proximal tubule epithelial- and fibroblast cells. Cisplatin was applied to this tricell culture model, and the secreted rescue signals were collected and used to induce MSCs. From these stress-induced MSCs, the (stress-induced) exosomes were collected and used for the cell-free therapeutic treatment of cisplatin-treated rats with acute kidney injury. The composition of the stress-induces exosomes was compared with the non-induced exosomes and found that the expression of some critical factors for cell proliferation, repair mechanism and oxidative stress was improved. The cisplatin-damaged renal tissue showed substantial recovery after the treatment with stress-induced exosomes compared to the treatment with non-induced exosomes. Although, the non-induced exosomes showed their activity mostly as cytoprotective, the induced exosomes further involved actively in the tissue regeneration, like MSCs. It was shown that the exosomes could be reprogrammed to improve their therapeutic effect to be used in cell-free regenerative medicine. Further, cisplatin-induced tissue damage in the kidney might be effectively prevented and used for tissue regeneration by use of induced exosomes generated for a particular damage.


Assuntos
Cisplatino , Exossomos , Ratos , Animais , Cisplatino/efeitos adversos , Exossomos/metabolismo , Reprodutibilidade dos Testes , Apoptose , Ratos Sprague-Dawley
13.
J Perianesth Nurs ; 37(6): 894-899, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35643890

RESUMO

PURPOSE: To test the validity and reliability of the Turkish version of the Children's Perioperative Multidimensional Anxiety Scale (CPMAS). DESIGN: Methodological research model. METHODS: One hundred children (81% male) aged 7 to 13 years undergoing elective surgery at a tertiary university hospital were included. Self-administered CPMAS and State-Trait Anxiety Inventory-Children were used to collect data at preoperative, operation day, and a month after the operation. Internal consistency, test-retest reliability, parallel form reliability, and content and construct validity of the tools were determined across all three visits. FINDINGS: The CPMAS demonstrated good test-retest reliability (ICC = 0.51 to 0.78) and good internal consistency (Cronbach's alpha = 0.78 to 0.81). Inter item correlation values were ranged from 0.20 to 0.62 at preoperative, 0.32 to 0.64 on the day of operation and 0.36 to 0.75 at a month after the operation. CPMAS single-factor construct and the explanatory percentages were 0.54 and above. After Pearson correlation analysis, CPMAS was moderately correlated with State-Trait Anxiety Inventory-Children at T1 (r = 0.54, P < .01) and T2 (r = 0.56, P < .01). CONCLUSIONS: The Turkish version of CPMAS has good reliability and validity score. Therefore, it is a suitable instrument to assess perioperative anxiety in 7 to 13 years old children in a clinical setting.


Assuntos
Transtornos de Ansiedade , Ansiedade , Humanos , Masculino , Criança , Adolescente , Feminino , Reprodutibilidade dos Testes , Universidades , Procedimentos Cirúrgicos Eletivos , Inquéritos e Questionários
14.
Turk J Biol ; 45(3): 301-313, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34377054

RESUMO

Selective targeting of transfected mesenchymal stem cells (MSCs) carrying specific antioncogenes to the tumor was suggested as a treatment option. Bone morphogenetic protein-2 (BMP2) was shown to inhibit the proliferation and aggressiveness of osteosarcoma (OS) cells. Here, we aimed to assess the homing efficiency of intraperitoneally administered hMSCs transfected with BMP2 to the tumoral site and their effects on OS using an orthotopic xenograft murine model. Orthotopic xenograft murine model of OS in six-week-old female NOD/SCID mice using 143B cells was established. hMSCs transfected with BMP2 (BMP2+hMSC) were used. In vivo experiments performed on four groups of mice that received no treatment, or intraperitoneally administered BMP2, hMSCs, and BMP2+hMSCs. Histopathological and immunohistochemical studies were used to evaluate the pathological identification and to assess the dimensions and necrotic foci of the tumor, the features of lung metastases, and immunostaining against p27, Ki-67, and caspase-3 antibodies. The osteogenic differentiation markers BMP2, BMP4, COL1A1, OPN, OCN and PF4 evaluated using RT-PCR. The tumor dimensions in the hMSCs group were significantly higher than those of the remaining groups (p < 0.01). The number of metastatic foci in the BMP2+hMSCs group was significantly lower than those of the other groups (p < 0.01). The current results showed that the intraperitoneal route could be efficiently used for targeting hMSCs to the tumoral tissues for effective BMP2 delivery. In this study, the effects of BMP2 transfected hMSCs on human OS and metastasis were promising for achieving osteogenic differentiation and reduced metastatic process.

15.
Future Oncol ; 17(25): 3373-3381, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34291649

RESUMO

Aim: To assess the anxiety levels of breast cancer patients during the COVID-19 pandemic. Materials & methods: A total of 298 patients completed the State-Trait Anxiety Inventory (STAI-S and STAI-T) and the Visual Analogue Scale for Anxiety (VAS) and VAS for Anxiety in COVID-19 (VAS-CoV). Results: 144 patients were in the high anxiety category for STAI-S, and 202 patients were in the high anxiety category for STAI-T. STAI-T score was significantly high in the metastatic group (p = 0.017). VAS-CoV score in the hormonotherapy group was significantly higher than in the no-treatment group (p = 0.023). There was a positive correlation between VAS-CoV and VAS levels (r = 0.708, p < 0.001), VAS-CoV and STAI-S and STAI-T scores (r = 0.402, p < 0.001; r = 0.185, p = 0.001, respectively), and a negative correlation between education years and STAI-T scores (r = -0.172, p = 0.003). Conclusion: The COVID-19 pandemic is related to high anxiety levels in breast cancer patients.


Lay abstract COVID-19 pandemic is related to rapidly rising anxiety levels worldwide. Because of the high mortality of COVID-19 in cancer patients, changing treatment routines and disruptions of the healthcare system, cancer patients are the most affected population in this situation. Anxiety among females and breast cancer patients tend to be high, although anxiety levels in cancer patients during the pandemic period varies according to the cancer type, treatment status and sociodemographic factors. This study assessed the effect of the COVID-19 pandemic on breast cancer patients' anxiety levels according to treatment status and stage of the disease. A total of 298 breast cancer patients completed the universally validated anxiety questionnaires. Results demonstrated high trait anxiety in breast cancer patients, particularly in the metastatic group. The current findings highlighted the importance of intensive assessment and close monitoring of breast cancer patients' psychological situations. It is crucial to provide psychological support to breast cancer patients to contribute to both treatment and follow-up processes during the pandemic.


Assuntos
Ansiedade/epidemiologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/psicologia , COVID-19/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Ansiedade/diagnóstico , Ansiedade/terapia , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/terapia , COVID-19/virologia , Comorbidade , Estudos Transversais , Gerenciamento Clínico , Feminino , Humanos , Pessoa de Meia-Idade , Vigilância em Saúde Pública , SARS-CoV-2 , Fatores Socioeconômicos , Turquia/epidemiologia
16.
Support Care Cancer ; 29(12): 7411-7420, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34075455

RESUMO

PURPOSE: The aims of the current study are to describe the quality of life among patients with rectal cancer and to determine the clinical and demographic correlation that influences the quality of life of rectal cancer patients. METHOD: In this study, 50 patients with rectal cancer treated in the Radiation Oncology Department of Kayseri City Education and Research Hospital were included. Ethics committee approval was received for the study. Data collection form was used to determine the demographic and clinicopathological characteristics of the patients. To assess the quality of life, the European Committee of Cancer Treatment and Organization Quality of Life Scale (EORTC QLQ-C30) question-answer scale was used. The data were collected by interviewing the patients face to face. Mann-Whitney U and Kruskal-Wallis tests were used to analyze the data. Spearman correlation analysis was performed to reveal the relationship between dependent variables. RESULTS: As a result of this study, 52% of patients were 65 years and older and 54% were male patients. The most common surgery was low anterior resection and the most common type of pathology was adenocarcinoma. According to American Cancer Committee (AJCC) 7th edition 2009 staging, 80% stage 3 was the most common. In EORTC C30 Cancer Quality of Life Scale Functional Scale Subscale, the highest score is from the physical function and the lowest score is from the emotional function. In the symptom scale subscale, the most common symptom was nausea/vomiting. Performance status (ECOG) was found to be significantly associated with T stage, N stage, TNM stage, and symptom scores. There was a moderately significant positive correlation between symptom scales and global health status scales (ρ = 0.51; p < 0.001). There was a perfectly positive and significant relationship between symptom scales and functional scales (ρ = 0.83; p < 0.001). CONCLUSIONS: As a result of this study we conducted, it was observed that rectal cancer patients decreased performance status and increased symptoms in the presence of advanced disease. Accordingly, it was found that the quality of life of the patient decreased.


Assuntos
Qualidade de Vida , Neoplasias Retais , Nível de Saúde , Humanos , Masculino , Estadiamento de Neoplasias , Neoplasias Retais/epidemiologia , Neoplasias Retais/terapia , Inquéritos e Questionários
17.
Exp Eye Res ; 208: 108612, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33992625

RESUMO

It has been reported that citicoline increases antioxidant activity in some tissues. However, the effect of citicoline on corneal wound-healing has not yet been demonstrated. The aim was to investigate the protective effects of citicoline on ultraviolet B (UVB) radiation-induced corneal oxidative damage in a rat model. Four groups (eight animals each) were investigated: controls; UVB only; UVB/citicoline; and citicoline only. Corneal oxidative damage was induced by exposure to UVB radiation at 560 µW/cm2 for five days in the UVB-exposed groups and 1% citicoline eye drops were applied (3xday) for eight days in the two citicoline groups. Corneal surface damage was evaluated by opacity and fluorescein staining. Corneal injury was assessed biochemically by measuring the concentrations of glutathione (GSH) and malondialdehyde (MDA) and the activity of corneal superoxide dismutase (SOD) and catalase. Matrix metalloproteinase (MMP) -2 and -9 and caspase-3 were evaluated by immunofluorescent staining and microscopic examination and by Western blot analysis. Corneal gene expression analysis was performed for vascular endothelial growth factor (VEGF), interleukin-1 beta (IL-1ß) and transforming growth factor-beta (TGF-ß). UVB radiation caused significant epithelial damage and evident opacity in the cornea, together with a local decrease in SOD, catalase and GSH activity. Corneal MDA concentrations increased with UVB exposure. The UVB/Citicoline group had significantly less corneal damage, greater SOD, catalase and GSH activity, and decreased MDA concentrations compared to the UVB only group (p < 0.05). Expression of TGF-ß, IL-1ß and VEGF was significantly lower in the citicoline/UVB group compared to the UVB group (p < 0.05). Interestingly, TGF-ß expression was lower in the citicoline only group compared with controls. Immunfluorescent staining and Western blot analysis showed increased MMP-2, -9 and caspase-3 in the UVB only group compared with the UVB/citicoline group. It was shown that citicoline treatment may be effective in suppressing oxidative stress and controlling inflammation in UVB corneal injury.


Assuntos
Córnea/metabolismo , Lesões da Córnea/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Tiofenos/administração & dosagem , Animais , Córnea/efeitos dos fármacos , Córnea/patologia , Lesões da Córnea/metabolismo , Lesões da Córnea/patologia , Modelos Animais de Doenças , Expectorantes , Masculino , Soluções Oftálmicas/administração & dosagem , Ratos , Ratos Wistar , Raios Ultravioleta/efeitos adversos
18.
Surg Laparosc Endosc Percutan Tech ; 31(1): 76-84, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32910108

RESUMO

BACKGROUND: In this study, we applied the ultra-mini percutaneous hepatolithotomy (UM-PHL) technique on hepatolithiasis patients with multiple and large stones on which other minimally invasive methods failed, and our aim was to report its results, sharing in series for the first time. MATERIALS AND METHODS: Preoperative and postoperative data, laboratory parameters, radiologic findings, and preoperative and postoperative details were recorded for a total of 14 patients for whom the UM-PHL technique was applied between April 2017 and December 2019. As all patients had multiple stones and extreme stone load and had bile duct surgery, they did not have a normal anatomy. All patients were radiologically confirmed to have had preprocedural magnetic retrograde cholangiopancreatography. RESULTS: Operation duration of the patients was 137.6±44.9 minutes, while intraoperative blood loss was 69.2±24.9 mL, drainage catheter removal time was 2.85±0.86 days, and the hospitalization time was 4.28±2.55 days. Intraoperative balloon dilation was applied to enlarge the stricture area in 5 patients (35.7%). On the basis of the Clavien-Dindo classification, grade 2 complication was observed in 2 patients (14.2%) due to postoperative cholangitis. Patients were followed up for an average of 15 months, and nonsymptomatic radiologic stone recurrence was detected in the 12th month control of 1 patient (7.1%). CONCLUSION: The UM-PHL technique is a successful method that facilitates stone clearance by providing minimal dilatation through percutaneous intervention and by using instruments with small diameter, and it can safely be applied with its low complication level, low recurrence ratio, and short hospitalization time.


Assuntos
Litíase , Hepatopatias , Cateterismo , Colangiopancreatografia Retrógrada Endoscópica , Dilatação , Humanos , Litíase/diagnóstico por imagem , Litíase/cirurgia , Hepatopatias/diagnóstico por imagem , Hepatopatias/cirurgia , Resultado do Tratamento
19.
J Craniofac Surg ; 31(5): 1469-1473, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32209927

RESUMO

PURPOSE: The main objective of this study was to display the morphologic properties of the anterior clinoid process (ACP) in human fetuses in term of early childhood surgeries. METHODS: Twenty-four (10 females and 14 males) fetal cadavers aged from 16th to 28th weeks of gestation (at mean, 21.54 ±â€Š3.11 weeks) were included in the present study. The dimensions of ACP were measured with a digital image analysis software. RESULTS: Taking into account the length, width, and angle of ACP, it was classified as Type 1 in 20.83% (10 cases), Type 2 in 10.42% (5 cases), Type 3 in 10.42% (5 cases), Type 4 in 2.08% (1 case), Type 5 in 8.33% (4 cases), Type 6 in 16.67% (8 cases), Type 7 in 8.33% (4 cases), and Type 8 in 22.92% (11 cases). According to the attachment site of the optic strut (OS) relative to ACP, OS was identified as the anterior 3/5 in 16.67% (8 cases), anterior 4/5 in 68.75% (33 cases), and posterior 1/5 in 14.58% (7 cases). Neither right-left nor male-female significant differences were observed between the quantitative values belonging to ACP and OS. CONCLUSION: The percentage of the most complex and challenging type of ACP (the long, narrow, and narrow-angled ACP) in fetuses was found to be close to adults. Thus, routine adult surgical procedures such as anterior clinoidectomy might be successfully used in young children and infants. The attachment site of OS relative to ACP in adults was more anterior according to fetuses probably due to postnatal development such as the pneumatization of the sphenoid bone. In this regard, for pediatric neurosurgeons to avoid iatrogenic injuries and to select appropriate surgical approaches, further studies conducted on the attachment of OS relative to ACP in children are needed.


Assuntos
Osso Esfenoide/embriologia , Osso Esfenoide/cirurgia , Cadáver , Olho , Feminino , Feto , Humanos , Masculino , Base do Crânio/cirurgia
20.
Comb Chem High Throughput Screen ; 23(10): 1064-1079, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32209039

RESUMO

AIMS: To prepare lamivudine (LAM)-loaded-nanoparticles (NPs) that can be used in lung cancer treatment. To change the antiviral indication of LAM to anticancer. BACKGROUND: The development of anticancer drugs is a difficult process. One approach to accelerate the availability of drugs is to reclassify drugs approved for other conditions as anticancer. The most common route of administration of anticancer drugs is intravenous injection. Oral administration of anticancer drugs may considerably change current treatment modalities of chemotherapy and improve the life quality of cancer patients. There is also a potentially significant economic advantage. OBJECTIVE: To characterize the LAM-loaded-NPs and examine the anticancer activity. METHODS: LAM-loaded-NPs were prepared using Nano Spray-Dryer. Properties of NPs were elucidated by particle size (PS), polydispersity index (PDI), zeta potential (ZP), SEM, encapsulation efficiency (EE%), dissolution, release kinetics, DSC and FT-IR. Then, the anticancer activity of all NPs was examined. RESULTS: The PS values of the LAM-loaded-NPs were between 373 and 486 nm. All NPs prepared have spherical structure and positive ZP. EE% was in a range of 61-79%. NPs showed prolonged release and the release kinetics fitted to the Weibull model. NPs structures were clarified by DSC and FT-IR analysis. The results showed that the properties of NPs were directly related to the drug:polymer ratio of feed solution. NPs have potential anticancer properties against A549 cell line at low concentrations and non-toxic to CCD 19-Lu cell line. CONCLUSION: NPs have potential anticancer properties against human lung adenocarcinoma cells and may induce cell death effectively and be a potent modality to treat this type of cancer. These experiments also indicate that our formulations are non-toxic to normal cells. It is clear that this study would bring a new perspective to cancer therapy.


Assuntos
Antirretrovirais/farmacologia , Antineoplásicos/farmacologia , Desenho de Fármacos , Lamivudina/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Nanopartículas/uso terapêutico , Administração Oral , Antirretrovirais/administração & dosagem , Antirretrovirais/química , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Lamivudina/administração & dosagem , Lamivudina/química , Neoplasias Pulmonares/patologia , Nanopartículas/administração & dosagem , Nanopartículas/química , Tamanho da Partícula , Propriedades de Superfície , Tecnologia Farmacêutica
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