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INTRODUCTION: Breast cancer is the most prevalent malignancy in women worldwide. Although pathogenic variants in the BRCA1/2 genes are responsible for the majority of hereditary breast cancer cases, a substantial proportion of patients are negative for pathogenic variations in these genes. In cancers, the signal transduction pathways of the cell are usually affected first. Therefore, this study aimed to detect and classified genetic variations in non-BRCA signaling genes and investigate the underlying genetic causes of susceptibility to breast cancer. METHODS: Ninety-six patients without pathogenic variants in the BRCA1/2 genes who met the inclusion criteria were enrolled in the study, and 34 genes were analyzed using next-generation sequencing (NGS) for genetic analysis. RESULTS: Based on the ClinVar database or American College of Medical Genetics criteria, a total of 55 variants of 16 genes were detected in 43 (44.8%) of the 96 patients included in the study. The pathogenic variants were found in the TP53, CHEK2, and RET genes, whereas the likely pathogenic variants were found in the FGFR1, FGFR3, EGFR, and NOTCH1 genes. CONCLUSION: The examination of signaling genes in patients who met the established criteria for hereditary breast cancer but were negative for BRCA1/2 pathogenic variants provided additional information for approximately 8% of the families. The results of the present study suggest that NGS is a powerful tool for investigating the underlying genetic causes of occurrence and progression of breast cancer.
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Neoplasias da Mama , Neoplasias de Mama Triplo Negativas , Humanos , Feminino , Neoplasias da Mama/genética , Neoplasias de Mama Triplo Negativas/genética , Predisposição Genética para Doença , Genes BRCA1 , Sequenciamento de Nucleotídeos em Larga Escala , Proteína BRCA1/genéticaRESUMO
BACKGROUND/AIM: To investigate the metabolic response and body mass index reduction according to the remaining stomach volume between 6-12 months after the operation in patients who underwent sleeve gastrectomy surgery for obesity and to determine the relationship between the remaining stomach volume and metabolic improvement. Materials and Methods: Patients underwent sleeve gastrectomy in a single center by the same team and with the same standardized method. Residual gastric volumes were calculated from three-dimensional computed tomography images obtained 6-12 months postoperatively. BMI, excess weight loss (EWL), total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL), very low density lipoprotein (VLDL), triglyceride, hemoglobin A1c (HbA1c), total protein, albumin values were recorded preoperatively and at the time of residual volume measurement. Results: There were 49 subjects with a mean SD preoperative BMI of 47.26+-6.21 kg/m2 and mean age 37.51+-10.88 years. Mean residual volume was 155.36+-56.71 cc. Residual volume was associated with postoperative mean BMI (28.44+-3.23 kg/m2; p 0.001) and postperative mean EWL%(29.27+-7.66; p=0.001). Residual gastric volume was also negative correlated with postoperative mean HbA1c (p=0.004). HbA1c (p=0.828), LDL (p=0.661), HDL (p=0.848), triglycerides (p=0.641), VLDL (p=0.794), total protein relation (p=0.539) and albumin (p=0.824) were analyzed before and after surgery and were not correlated with residual gastric volume. CONCLUSION: The smaller the residual gastric volume after laparoscopic sleeve gastrectomy, the higher the %EWL and the greater the decrease in HbA1c. This study show that laparoscopic sleeve gastrectomy is an effective surgical procedure in patients with Type 2 diabetes mellitus.
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Diabetes Mellitus Tipo 2 , Humanos , Adulto , Pessoa de Meia-Idade , Índice de Massa Corporal , Hemoglobinas Glicadas , Volume Residual , Resultado do Tratamento , Estômago , Gastrectomia , AlbuminasRESUMO
High-fat diet-induced obesity adversely affects the female reproductive system. The metabolic changes that the high-fat diet causes on the ovaries have not been elucidated. Herein, to understand the molecular and cellular mechanisms underlying the effects of long-term high-fat diet-fed, the changes in the global proteomic profile of the rat ovaries were investigated. The female rats were randomly divided into two groups based on their diets: the ones that were fed with the high-fat diet and the other ones that were fed with the control diet for 18 weeks. To identify differentially expressed proteins, the changes in ovary proteomes were investigated by two-dimensional electrophoresis coupled to matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight and label-free quantification with nano-high performance liquid chromatography to tandem mass spectrometry (nHPLC-MS/MS). A total of 80 proteins were differentially regulated. The upregulated proteins were involved in responses to chemical and organic substances, cytokines, external stimuli, and lipids. These proteins were particularly associated with vesicles, microbodies, and cell surface proteins. The downregulated proteins were involved in biological processes associated with cellular respiration. Those proteins created a network consisting of proteins involved in aerobic respiration and energy generation. Our results demonstrated that the mechanisms related to energy production in the ovary tissue were particularly affected by the high-fat diet.
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Dieta Hiperlipídica , Proteoma , Animais , Dieta Hiperlipídica/efeitos adversos , Feminino , Obesidade/etiologia , Obesidade/metabolismo , Ovário/química , Proteoma/metabolismo , Proteômica/métodos , Ratos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Espectrometria de Massas em TandemRESUMO
BACKGROUND: More evidence shows that primary surgery for de novo metastatic breast cancer (BC) prolongs overall survival (OS) in selected cases. The aim of this study was to evaluate the role of locoregional treatment (LRT) in BC patients with de novo stage IV bone only metastasis (BOM). METHODS: The prospective, multicenter registry study BOMET MF14-01 was initiated in May 2014. Patients with de novo stage IV BOM BC were divided into two groups: those receiving systemic treatment (ST group) and those receiving LRT (LRT group). Patients who received LRT were further divided into two groups: ST after LRT (LRT + ST group) and ST before LRT (ST + LRT group). RESULTS: We included 505 patients in this study; 240 (47.5%) patients in the ST group and 265 (52.5%) in the LRT group. One hundred and thirteen patients (26.3%) died in the 34-month median follow-up, 85 (35.4%) in the ST group and 28 (10.5%) in LRT group. Local progression was observed in 39 (16.2%) of the patients in the ST group and 18 (6.7%) in the LRT group (p = 0.001). Hazard of death was 60% lower in the LRT group compared with the ST group (HR 0.40, 95% CI 0.30-0.54, p < 0.0001). CONCLUSION: In this prospectively maintained registry study, we found that LRT prolonged survival and decreased locoregional recurrence in the median 3-year follow-up. Timing of primary breast surgery either at diagnosis or after ST provided a survival benefit similar to ST alone in de novo stage IV BOM BC patients.
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Neoplasias da Mama , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Estudos Multicêntricos como Assunto , Metástase Neoplásica , Recidiva Local de Neoplasia/cirurgia , Sistema de Registros , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Graves' disease (GD) and toxic multinodular goitre (TMNG) are the most common thyroid diseases which mainly lead to thyrotoxicosis, however, the underlying mechanism of distinct clinical presentations remains unclear. Protein extracts from the thyroid tissue specimens of the patients with GD and TMNG were subjected to Difference Gel Electrophoresis (DIGE). Differentially regulated protein spots were determined by image analysis, and the spots displaying statistically significant differences were identified by Matrix-Assisted Laser Desorption Ionization Time of Flight Mass Spectrometer (MALDI-TOF) followed by MASCOT search. Western blot analysis was used to verify changes occurring at the protein levels. The identified proteins were classified based on their functions in metabolic pathways using bioinformatics algorithms. Fifteen proteins showed significant alterations in abundance between the two disease groups. Bioinformatic analysis revealed the differentially regulated proteins were particularly related to catabolism, oxidative stress and especially energy utilization pathways, including glycolysis, proteolysis, ketone body catabolism and other energy metabolism-related pathways. SIGNIFICANCE OF THE STUDY: Previously, GD has been the subject of many studies that performed the proteomics approaches in the orbital tissue samples or tear. This is one of the very few studies that investigate the changes in the proteome of thyroid tissue in GD. We demonstrated mainly the upregulation of catabolic activity-related proteins in patients with GD compared to TMNG. Although it remains to be elucidated, some of these proteins can be used as markers for GD or have a role in the pathogenesis of the disease. Our study contributes the increasing data over time by providing new biomarker candidates for GD.
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Bócio Nodular/metabolismo , Doença de Graves/metabolismo , Proteínas/análise , Proteômica , Glândula Tireoide/metabolismo , Adulto , Biologia Computacional , Feminino , Bócio Nodular/patologia , Doença de Graves/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas/metabolismo , Glândula Tireoide/química , Glândula Tireoide/patologiaRESUMO
BACKGROUND: The aim of the study was to evaluate the role of well-characterized vitamin D receptor (VDR) gene polymorphisms, BsmI (rs 1544410), ApaI (rs 7975232), TaqI (rs 731236), and FokI (rs 10735810) and their haplotypes in the pathogenesis of breast cancer in Turkish women. METHODS: The subjects consisted of women including 331 breast cancer patients and 345 healthy controls. After conventional DNA isolation genotyping was done by a PCR-RFLP method, haplotype analysis was performed using Haploview 4.2. RESULTS: Haplotype analysis in different combinations revealed that frequencies of Fbt, fbt, bAt, and bt haplotypes are significantly higher in breast cancer patients than controls (χ2 = 6.862, p = 0.0088; χ2 = 4.176, p = 0.041; χ2 = 4.184, p = 0.0408; χ2 = 8.409, p = 0.0037 respectively). However, no statistically significant difference between genotypes of cases and controls were found when analyzed separately. CONCLUSIONS: All these data support the hypothesis that it is crucial to evaluate VDR gene polymorphism by haplotype analysis in order to understand how changes in VDR sequence influence the function of the VDR gene and how this variability affects the risk of breast cancer.
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Neoplasias da Mama , Receptores de Calcitriol , Neoplasias da Mama/genética , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Genótipo , Haplótipos , Humanos , Receptores de Calcitriol/genética , Vitamina DRESUMO
Background and objectives: Sentinel lymph node biopsy is important for metastasis surveillance in the management of a number of human cancers. Identification of sentinel lymph nodes may be facilitated by the use of several methods including methylene blue injection. However tissue necrosis is a known effect of methylene blue application. This study aimed to investigate the effects of methylene blue injection on skin flaps using a rodent model.Methods: Modified McFarlane flaps were prepared using Wistar Albino rats. Local injection of methylene blue was given to one group while saline was injected into the control group. A third group received systemic methylene blue via intraperitoneal injection. Observational and histological comparison was made between the groups to investigate the necrotic effects of methylene blue on skip flaps.Results: The control group's surviving flap areas were significantly larger than local methylene blue group's surviving flap area. However, there was no significant difference in skin flap survival area between the control group and the systemic methylene blue group. Furthermore, there is no significant difference between local and systemic methylene blue group's surviving flap areas.Conclusions: Local methylene blue injection increases skin necrosis and decreases rates of surviving flap areas in an experimental rat models.
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Sobrevivência de Enxerto/efeitos dos fármacos , Azul de Metileno/efeitos adversos , Transplante de Pele , Pele/efeitos dos fármacos , Pele/patologia , Retalhos Cirúrgicos , Animais , Modelos Animais de Doenças , Masculino , Azul de Metileno/administração & dosagem , Ratos , Ratos WistarRESUMO
OBJECTIVE: Breast cancer is one of the most devastating cancer types affecting women. For critical decision making regarding the fate of cancerous breast tissue, the assessment of axillary lymph node (ALN) involvement is required. However, such ALN involvement is difficult to predict without surgical intervention. Therefore, an easy predictive test using protein markers may be a desirable approach. In this study, we performed a whole proteome analysis to reveal the presence of a putative biomarker panel using primary breast tumor tissue. Materials and Methods: Proteins were extracted from tumor tissues and were subjected to two dimensional (2D) gel electrophoresis. The resulting gel images were used for inter-gel spot comparisons using PDQuest Advance software. The paterns thus obtained were used for differentiating invasive tumor types from non-invasive ones. Results: The analysis of 2D gel images revealed the presence of 24 conserved protein spots whose intensities were moderately regulated high on the gels. Those protein spots were used to create a conserved 2D pattern spanning a pH range of 4 to 8. CONCLUSION: Protein spots generating a preserved model among pattern between primary breast cancer and its axillary lymph node indicated that a robust and highly reliable proteomic approach, e.g., 2DE may be used to differentiate metastatic forms of breast cancer from non-metastatic ones.
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Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Proteoma/metabolismo , Biópsia de Linfonodo Sentinela , Adulto , Idoso , Axila/cirurgia , Neoplasias da Mama/metabolismo , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Valor Preditivo dos Testes , Sensibilidade e EspecificidadeRESUMO
PURPOSE: The purpose of this study was to investigate the correlation between the percentages of CD44+/CD24- cancer stem cells (CSCs) and the clinicopathological and prognostic factors in breast cancer patients. METHODS: Twenty three women who underwent surgery for breast cancer were enrolled in this study. The mean age of the patients was 46.65 years and 52% had early-stage disease. Tumor tissues obtained during surgery were digested enzymatically. CD44+/CD24- cell phenotype was identified by using surface marker antibodies and percentages were determined by surface marker expression of the cells. RESULTS: Sixty five percent of the tumors were positive for estrogen (ER)/ progesterone receptors (PR) and 38% of the tumors were positive for HER-2. All of the patients with hormone receptor positive tumors had ER positive tumors, while only 11 patients had PR positive breast cancer. CD44+/CD24- cells were present in all tumor tissues. The mean proportion of the CD44+/CD24- cells was 1.43±1.6. The mean percentages of CD18+ cells and MUC1+ were 27.9±26.5% and 6.07±11.34%, respectively. The percentage of CD18+ cells was significantly higher in PR positive tumors (p=0.042). There was no significant correlation between the percentage of CD44+/CD24- cells and clinicopathological features. CONCLUSION: This study showed that CD44+/CD24- cells were present in all tumor tissues. The percentage of CD44+/CD24- cells was higher in early-stage disease, yet without statistical significance. No correlation was found between prognostic factors and the percentage of the CD44+/CD24- cells.
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Biomarcadores Tumorais/análise , Neoplasias da Mama/imunologia , Antígeno CD24/análise , Receptores de Hialuronatos/análise , Células-Tronco Neoplásicas/química , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Mucina-1/análise , Estadiamento de Neoplasias , Células-Tronco Neoplásicas/patologia , Fenótipo , Receptor ErbB-2/análise , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Adulto JovemRESUMO
Congenital thyroid abnormalities are rarely seen. They mostly include hemiagenesis with or without involving the isthmus. In this report, we present a case of bilateral lobe agenesis with hypertrophied isthmus and high calcium and elevated PTH levels which were detected during routine examinations of a 49-year-old female patient. Some findings consistent with parathyroid pathology on the right side were determined in parathyroid scintigraphy. At thyroid scan and neck ultrasonography there was no sign of bilateral thyroid tissue except a mass localized isthmus. The right lower parathyroidectomy and thyroidectomy for isthmus were performed; the pathology report was shown as parathyroid adenoma and nodular colloidal goiter. This case of bilobar agenesis with incidental primary hyperparathyroidism due to single parathyroid adenoma is the first case reported in literature.
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Hiperparatireoidismo/etiologia , Neoplasias das Paratireoides/complicações , Glândula Tireoide/anormalidades , Cálcio/sangue , Feminino , Bócio Nodular/complicações , Humanos , Hipertrofia , Achados Incidentais , Pessoa de Meia-Idade , Glândulas Paratireoides/diagnóstico por imagem , Glândulas Paratireoides/patologia , Glândulas Paratireoides/cirurgia , Hormônio Paratireóideo/sangue , Neoplasias das Paratireoides/diagnóstico , Neoplasias das Paratireoides/patologia , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia , Cintilografia , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , TireoidectomiaRESUMO
BACKGROUND/AIMS: To evaluate association of serum lipids and fasting plasma glucose levels with colorectal cancer. METHODOLOGY: This prospective case control study was conducted with 347 patients with colorectal carcinoma and 310 age and gender matched healthy controls who were examined for annual check-up. Total cholesterol, serum lipids and fasting glucose levels were measured in both groups. Body weight and body mass indices were also evaluated. RESULTS: The mean serum cholesterol level was 167.4 +/- 43.6 mg/dL for patients with colorectal cancer and 210.1 +/- 30.7 mg/dL for controls. The mean fasting plasma glucose levels for both groups were respectively 107.7 +/- 22.4 and 90.2 +/- 10.3. Between the colorectal cancer and control groups, there was a statistically significant difference in fasting plasma glucose and serum lipid levels except LDL-C. Serum total cholesterol level was even lower in advanced stages of cancer. CONCLUSIONS: Our study suggests that there is an inverse association between low serum total cholesterol levels and colorectal cancer. Since cholesterol levels were lower in the advanced stages of colorectal cancer it is possible that low levels of serum cholesterol levels were a consequence of colorectal cancer. The association with hypertriglyceridemia and high fasting plasma glucose levels suggest the role of hyperinsulinemia in colorectal carcinogenesis.
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Neoplasias Colorretais/sangue , Lipídeos/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/análise , Índice de Massa Corporal , Peso Corporal , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
BACKGROUND/AIMS: Colorectal cancers are the most common cancers of the gastrointestinal system. A significant relationship was detected between the metastasis and tumor angiogenesis of colorectal cancer. The aim of the present study was to investigate the association between some cytokines and tumor stages. Additionally, association between VEGF gene polymorphisms and colorectal cancer was studied. METHODS: In this study, we measured serum IL-18, IL-2, VEGF, endothelin (ET), and nitric oxide (NO) levels in 44 patients with colorectal cancer and 44 healthy controls. Also we investigated VEGF G634C (rs2010963) and VEGF C936T (rs3025039) polymorphisms of VEGF gene in these groups by using a PCR-RFLP method. Data were analyzed statistically. RESULTS: Serum levels of IL-18, VEGF, IL-2 and NO were significantly higher in patients with colorectal cancer when compared to controls (p<0,05). Serum ET levels were found to be similar in colorectal cancer patients and healthy controls. When we compared the two subgroups constituted by tumor stages (Stage 1-2 and Stage 3-4) with each other, serum VEGF levels were found significantly higher in stage 3-4 group than stage 1-2 group (p<0,05). No significant difference was found between subgroups with regard to other parameters. We found that investigated VEGF G634C and VEGF C936T polymorphisms were not associated with the severity of colorectal cancer. (P=0.228 for VEGF G634-C; P= 0.484 for VEGF C936-T) CONCLUSION: In the future, serum levels of IL-18, VEGF, IL-2 and NO may be a useful marker for diagnosis of patients with colorectal cancer. Additionally we consider that serum VEGF levels can be used as a tumor marker to predict prognosis of cancer. However, larger studies with long-term follow-up are necessary to clarify this hypothesis. On the other hand, there is necessity for the new studies for determination of association between VEGF gene polymorphism and colorectal cancer.
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Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias Colorretais/diagnóstico , Citocinas/sangue , Polimorfismo Genético , Fator A de Crescimento do Endotélio Vascular/genética , Estudos de Casos e Controles , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Endotelinas/sangue , Predisposição Genética para Doença , Humanos , Interleucina-18/sangue , Interleucina-2/sangue , Estadiamento de Neoplasias , Óxido Nítrico/sangue , Fenótipo , Fator A de Crescimento do Endotélio Vascular/sangueRESUMO
Stress response caused by events such as surgical trauma includes endocrine, metabolic and immunological changes. Stress hormones and cytokines play a role in these reactions. More reactions are induced by greater stress, ultimately leading to greater catabolic effects. Cuthbertson reported the characteristic response that occurs in trauma patients: protein and fat consumption and protection of body fluids and electrolytes because of hypermetabolism in the early period. The oxygen and energy requirement increases in proportion to the severity of trauma. The awareness of alterations in amino acid, lipid, and carbohydrate metabolism changes in surgical patients is important in determining metabolic and nutritional support. The main metabolic change in response to injury that leads to a series of reactions is the reduction of the normal anabolic effect of insulin, i.e. the development of insulin resistance. Free fatty acids are primary sources of energy after trauma. Triglycerides meet 50 to 80 % of the consumed energy after trauma and in critical illness. Surgical stress and trauma result in a reduction in protein synthesis and moderate protein degradation. Severe trauma, burns and sepsis result in increased protein degradation. The aim of glucose administration to surgical patients during fasting is to reduce proteolysis and to prevent loss of muscle mass. In major stress such as sepsis and trauma, it is important both to reduce the catabolic response that is the key to faster healing after surgery and to obtain a balanced metabolism in the shortest possible time with minimum loss. For these reasons, the details of metabolic response to trauma should be known in managing these situations and patients should be treated accordingly.
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Glycerol-3-phosphate dehydrogenase (GPD1) and monoacylglycerol lipase (MAGL) levels are known to be significantly downregulated in both the tissue and serum samples of patients with triple-negative breast cancer (TNBC), compared with other BC subtypes and healthy controls. As such, the association between GPD1 and MAGL levels and lymph node metastasis was evaluated in the present study. Utilizing western blotting, lymph node protein extracts from metastasized BC subtypes were analyzed and a significant downregulation of GPD1 and MAGL protein expression levels in the lymph node metastases was demonstrated in the TNBC subtype, compared with healthy controls. This finding further highlighted the potential use of these two proteins in early BC onset and metastasis detection.
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BACKGROUND: This study presents the diagnosis and treatment of rare small bowel tumors through clinical cases. METHODS: Patients treated between 2000 and 2023 were included in the study. The clinical records of the patients were analyzed retrospectively. RESULTS: A total of 34 patients were included in the study. Of these patients, 26 (75.5%) were male and eight (23.5%) were female. The mean age of the patients was 62.1 years. The most common symptoms and signs were abdominal pain (76.4%), bloating (38.2%), and nausea and vomiting (17.6%). Diagnostic methods included computed tomography (CT) (82.3%), upper gastrointestinal double balloon enteroscopy (35.2%), and capsule endoscopy (5.8%). Diagnoses included adenocarcinoma in 13 cases, gastrointestinal stromal tumors (GISTs) in 12 cases, and neuroendocrine tumors (NETs) in two cases. CONCLUSION: Small bowel tumors frequently present with abdominal pain, bloating, and nausea and vomiting. CT and endoscopic procedures are the primary diagnostic tools. Small bowel cancers are often diagnosed late due to subtle clinical findings and the limitations of endoscopic imaging. Targeted screening strategies may be beneficial for certain at-risk and symptomatic patient groups. Early surgical intervention offers significant advantages for diagnosed patients.
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Endoscopia por Cápsula , Neoplasias Intestinais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Intestinais/diagnóstico , Neoplasias Intestinais/cirurgia , Dor Abdominal/etiologia , Vômito , NáuseaRESUMO
BACKGROUND: N-Nitrosomorpholine (NMO) is one of the most common N-nitroso compounds. An oncocytic transformation has been demonstrated in renal tubules of NMO-treated rats. In our study, we aimed to investigate the potential transformation of oncocytic cells in 6 endocrine organs, i.e., thyroid, adrenal and pituitary glands, pancreas, testis, and bone, of NMO-exposed rats. METHODS: Thirty male rats were born and raised. Fifteen of them were given a single dose of 320 mg NMO per kg body weight, dissolved in drinking water, by a gavage tube. At the end of 52 weeks, the animals in both series were killed. Right after the killing, 6 different endocrine organs (hypophysis, thyroid, pancreas, adrenal gland, bone [femur], and testicles) of each animal were excised. RESULTS: There was no evidence of oncocytic cell development in the control group. In contrast, oncocytes were observed in 8 out of 13 NMO-treated rats: 2 in the adrenal sections, 1 in the thyroid sections, 3 in the pituitary sections, and 2 in the pancreas sections. Thesticle and bone sections were completely normal. CONCLUSIONS: We showed that NMO induced an oncocytic change in pancreas, thyroid, pituitary, and adrenal glands. To date, no identified specific environmental risk factors that lead to an oncocytic transformation in endocrine glands have been reported previously. Given the increasing prevalence of endocrine-disrupting chemicals in the environment, personal care products, manufactured goods, and food sources, there is a need to advance our understanding of the pathological mechanisms underlying oncocytosis in endocrine organs.
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Nitrosaminas , Células Oxífilas , Ratos , Masculino , Animais , Células Oxífilas/patologia , Nitrosaminas/toxicidade , Glândula Tireoide , Glândulas SuprarrenaisRESUMO
Objectives: The involvement of axillary lymph nodes plays a key role in breast cancer staging. Positron emission tomography is a promising modality for detecting axillary lymph node metastasis. In addition, nomograms are used to predict the status of axillary lymph nodes. In this study, the role of positron emission tomography in determining axillary metastasis and its correlation with the nomogram was evaluated. Material and Methods: The axillary maximum standard uptake value (SUVmax) values of the patients in the preoperative period, the features in the perioperative and postoperative specimen and Memorial Sloan Kettering Cancer Center nomogram data were evaluated. Results: As axillary SUVmax detected by Positron emission tomography in the preoperative period increased, so did the likelihood of lymph node involvement. Axillary SUVmax value were compared with Memorial Sloan Kettering Cancer Center nomogram data but no correlation was found. Age, lymph node number, histopathology results, mass diameter, presence or absence of lymphovascular invasion and/or perineural invasion, tumor type, estrogen receptor status, Ki67 and Cerb-B2 statuses were not correlated. However, axillary SUVmax was inversely correlated with grade and progesterone receptor status. Conclusion: Results from positron emission tomography of axillary lymph nodes in breasts cancer patients showed that SUVmax was only inversely related to cancer grade and progesterone receptor status while not correlating with other accepted parameters for tumor assessment. Thus there is insufficient reliability for the use of axillary SUVmax alone for accurate assessment of tumor characteristics at present.
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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.
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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/químicaRESUMO
Hydatid disease (HD) is a zoonotic disease, which typically affects the liver and the lungs. Primary retroperitoneal localization of the disease is infrequent. The most common symptom is abdominal pain; however, the clinical features of HD may be generally dependent on the location of the cyst. A 53-year-old female patient presented to Kocaeli University General Surgery Clinic, Turkey in September 2019 with complaints of flank pain, constipation and vomiting. The MRI revealed cystic lesions in the pancreas and psoas muscle. Both cysts were excised totally during laparotomy. Histopathology reports showed that the lesion in psoas muscle was hydatid cyst whereas the lesion in pancreas was pancreatic pseudocyst. Postoperative period was uneventful and the patient was discharged with albendazole treatment. No recurrence occurred during follow-up period. Atypical localization for hydatid disease is a diagnostic dilemma for surgeons, especially in endemic countries. Hydatid disease should always be considered in the differential diagnosis of retroperitoneal lesions, inadequate management can lead to complications and fatalities. Surgery combined with antiparasitic therapy, may be an option in the presence of obstruction of gastrointestinal and/or urinary tract.
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Idiopathic Granulomatous Mastitis (IGM) is a disease that clinically mimics breast cancers with symptoms of pain, edema, erythema, nipple discharge, nipple retraction, and fistula. Although IGM is considered to be formed by autoimmune responses or infections, the molecular mechanism behind formation and progress is unknown. Therefore, in this study, we aimed to investigate molecular mechanisms underlying IGM formation, progress, and recurrence by monitoring the changes at the proteome level. Protein extracts prepared from IGM (n = 15) and within-control tissues (n = 15) were subjected to nHPLC followed by LC-MS/MS proteomic analysis. Label-free quantitation analysis revealed that sixty differentially regulated between the two groups. Those proteins were classified based on their role in metabolic pathways using bioinformatics tools. Based on DAVID analysis, 16 of the differently regulated proteins were associated with the immune system, while 17 proteins were involved in cancer metabolism. STRING analysis showed that five of the differentially regulated proteins were associated with combined immune deficiency which were PNP, TAP1, ITGAL, PRKDC, and PTPRC while the other proteins were involved in insulin response and neutrophil degranulation. This study is one of the very few studies that investigated the changes in protein expressions of IGM tissues compared to controls. For the first time, we have shown the relationship of IGM with the immune system at the protein level and also underlined the cancer-like behavior of the disease. Furthermore, the proteins that were pointed out as combined immune deficiency-related proteins may have value as diagnostic markers for idiopathic granulomatous mastitis although further studies are needed to shed more light on the pathogenesis of the disease.