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1.
STAR Protoc ; 5(2): 103132, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38875112

RESUMO

The mandatory usage of extracellular matrix (ECM) gels in 3D cultures limits antibody penetration and increases background, while the removal of ECM gel causes disruption of morphology and sample loss. These factors pose challenges to effective immune labeling-based staining. Here, we present a protocol for whole-mount immunofluorescence staining of gel-embedded pancreatic organoids. We describe steps for sample fixation, blocking, and antibody incubation. We detail procedures for washing antibodies and mounting.


Assuntos
Matriz Extracelular , Imunofluorescência , Organoides , Pâncreas , Organoides/citologia , Organoides/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/química , Pâncreas/citologia , Pâncreas/metabolismo , Imunofluorescência/métodos , Animais , Coloração e Rotulagem/métodos , Humanos , Géis/química , Camundongos
2.
J Matern Fetal Neonatal Med ; 37(1): 2326304, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38499386

RESUMO

OBJECTIVE: Endothelial dysfunction is a major feature of preeclampsia. sVE-cadherin plays a role in the preservation and regulation of the endothelial barrier. For that reason, to evaluation of sVE-cadherin may help elucidate the disease pathophysiology of preeclampsia. METHODS: The sample size was calculated as a minimum of 46 pregnant women for each group based on serum sVE-Cadherin levels in a pilot study of 10 preeclamptic and 10 control groups. Hundred-twenty pregnancies complicated with early-onset (n = 60) and late-onset (n = 60) preeclampsia were compared with 120 gestational-age (GA)-matched (±1 week) uncomplicated pregnancies. The venous blood sampling was performed upon preeclampsia diagnosis prior to the onset of the labor in the preeclampsia group and the matching (±1 week) pregnancy week in the control group. Demographic and biochemical parameters were evaluated. RESULTS: Mean serum sVE-Cadherin was significantly higher in women with EOPE compared to that of the GA-matched control group (5.86 ± 1.57 ng/mL vs. 2.28 ± 0.80 ng/mL, p < 0.001), in women with LOPE compared to that of the GA-matched control group (3.11 ± 0.97 ng/mL vs. 1.69 ± 0.87 ng/mL, p < 0.001), and in women with EOPE compared to that of LOPE group (5.86 ± 1.57 ng/mL vs. 3.11 ± 0.97 ng/mL, p < 0.001) after correction for GA. Serum sVE-Cadherin positively correlated with systolic and diastolic blood pressure and a negative correlation with gestational age at sampling. CONCLUSION: The serum level of sVE-Cadherin was higher in women with preeclampsia than that of GA-matched healthy pregnant women, in women with EOPE compared to that of LOPE. sVE-Cadherin is an important marker in early-onset pre-eclampsia with severe clinical findings.


Assuntos
Amarelo de Eosina-(YS)/análogos & derivados , Fosfatidiletanolaminas , Pré-Eclâmpsia , Gravidez , Humanos , Feminino , Projetos Piloto , Pressão Sanguínea , Estudos de Casos e Controles , Caderinas
4.
J Clin Invest ; 133(21)2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37607005

RESUMO

Solid cancers like pancreatic ductal adenocarcinoma (PDAC), a type of pancreatic cancer, frequently exploit nerves for rapid dissemination. This neural invasion (NI) is an independent prognostic factor in PDAC, but insufficiently modeled in genetically engineered mouse models (GEMM) of PDAC. Here, we systematically screened for human-like NI in Europe's largest repository of GEMM of PDAC, comprising 295 different genotypes. This phenotype screen uncovered 2 GEMMs of PDAC with human-like NI, which are both characterized by pancreas-specific overexpression of transforming growth factor α (TGF-α) and conditional depletion of p53. Mechanistically, cancer-cell-derived TGF-α upregulated CCL2 secretion from sensory neurons, which induced hyperphosphorylation of the cytoskeletal protein paxillin via CCR4 on cancer cells. This activated the cancer migration machinery and filopodia formation toward neurons. Disrupting CCR4 or paxillin activity limited NI and dampened tumor size and tumor innervation. In human PDAC, phospho-paxillin and TGF-α-expression constituted strong prognostic factors. Therefore, we believe that the TGF-α-CCL2-CCR4-p-paxillin axis is a clinically actionable target for constraining NI and tumor progression in PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Animais , Camundongos , Fator de Crescimento Transformador alfa/genética , Fator de Crescimento Transformador alfa/metabolismo , Paxilina/genética , Paxilina/metabolismo , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/metabolismo , Fenótipo , Linhagem Celular Tumoral , Neoplasias Pancreáticas
5.
Turk J Gastroenterol ; 33(8): 627-663, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35993526

RESUMO

Colorectal cancer is the third most common cancer in Turkey. The current guidelines do not provide sufficient information to cover all aspects of the management of rectal cancer. Although treatment has been standardized in terms of the basic principles of neoadjuvant, surgical, and adjuvant therapy, uncertainties in the management of rectal cancer may lead to significant differences in clinical practice. In order to clarify these uncertainties, a consensus program was constructed with the participation of the physicians from the Acibadem Mehmet Ali Aydinlar and Koç Universities. This program included the physicians from the departments of general surgery, gastroenterology, pathology, radiology, nuclear medicine, medical oncology, radiation oncology, and medical genetics. The gray zones in the management of rectal cancer were determined by reviewing the evidence-based data and current guidelines before the meeting. Topics to be discussed consisted of diagnosis, staging, surgical treatment for the primary disease, use of neoadjuvant and adjuvant treatment, management of recurrent disease, screening, follow-up, and genetic counseling. All those topics were discussed under supervision of a presenter and a chair with active participation of related physicians. The consensus text was structured by centralizing the decisions based on the existing data.


Assuntos
Neoplasias Retais , Terapia Combinada , Consenso , Humanos , Oncologia , Terapia Neoadjuvante , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Neoplasias Retais/terapia
6.
Chin Clin Oncol ; 11(1): 5, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35255694

RESUMO

BACKGROUND AND OBJECTIVE: Pancreatic cancer is an aggressive disease with an impaired survival despite improvements in clinical management. Thus, understanding disease biology is of vital importance in order to overcome therapeutic challenges and achieve better prognosis. The purpose of this review is to outline the genetic landscape of pancreatic cancer along with its clinical implications. METHODS: We reviewed existing literature using electronic databases to outline the genetic landscape in pancreatic cancer. KEY CONTENT AND FINDINGS: This review mainly contains information on the genetic background of pancreatic cancer, mainly KRAS, CDKN2A, TP53 and SMAD4, with emphasis on the importance of understanding disease biology. CONCLUSIONS: The genetic aspects of pancreatic cancer have been well described especially with the introduction of next generation sequencing techniques. Future studies focusing on translation of these alterations in clinical application might pave the way for personalized surveillance and therapy.


Assuntos
Neoplasias Pancreáticas , Proteína Supressora de Tumor p53 , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Humanos , Mutação , Neoplasias Pancreáticas/genética , Prognóstico , Proteína Supressora de Tumor p53/genética
8.
Z Geburtshilfe Neonatol ; 226(3): 178-185, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35181881

RESUMO

OBJECTIVE: To evaluate the serum vasostatin-1 levels in preeclamptic and non-preeclamptic pregnant women. MATERIALS AND METHODS: Thirty consecutive women with mild preeclampsia and sixty consecutive women with severe preeclampsia were compared with ninety gestational age-matched (±1 week) non-preeclamptic pregnant women with an appropriate-for-gestational-age (AGA) fetus. RESULTS: Mean serum vasostatin-1 was significantly higher in women with preeclampsia than gestational age-matched controls. Mean serum vasostatin-1 was significantly higher in the mild preeclampsia group compared to its gestational age-matched control group, and in the severe preeclampsia group compared to its gestational age-matched control group. There was no significant difference in mean serum vasostatin-1 levels between the mild and severe preeclampsia groups, and in severe early- and severe late-onset preeclampsia groups. Serum vasostatin-1 had positive correlations with systolic and diastolic blood pressure. CONCLUSION: Serum vasostatin-1 was significantly higher in women with preeclampsia compared to those of the gestational age-matched controls. There was no significant difference in mean serum vasostatin-1 levels between the mild and severe preeclampsia groups and severe early- and severe late-onset preeclampsia groups.


Assuntos
Cromogranina A , Fragmentos de Peptídeos , Pré-Eclâmpsia , Pressão Sanguínea/fisiologia , Estudos de Casos e Controles , Cromogranina A/sangue , Feminino , Idade Gestacional , Humanos , Fragmentos de Peptídeos/sangue , Pré-Eclâmpsia/diagnóstico , Gravidez
9.
JCI Insight ; 7(1)2022 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-35014625

RESUMO

KRAS mutations are the drivers of various cancers, including non-small cell lung cancer, colon cancer, and pancreatic cancer. Over the last 30 years, immense efforts have been made to inhibit KRAS mutants and oncogenic KRAS signaling using inhibitors. Recently, specific targeting of KRAS mutants with small molecules revived the hopes for successful therapies for lung, pancreatic, and colorectal cancer patients. Moreover, advances in gene editing, protein engineering, and drug delivery formulations have revolutionized cancer therapy regimens. New therapies aim to improve immune surveillance and enhance antitumor immunity by precisely targeting cancer cells harboring oncogenic KRAS. Here, we review recent KRAS-targeting strategies, their therapeutic potential, and remaining challenges to overcome. We also highlight the potential synergistic effects of various combinatorial therapies in preclinical and clinical trials.


Assuntos
Antineoplásicos , Sistemas de Liberação de Medicamentos , Genes ras , Neoplasias , Proteínas Proto-Oncogênicas p21(ras) , Animais , Humanos , Camundongos , Mutação , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo
10.
J Obstet Gynaecol ; 42(1): 55-60, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33938370

RESUMO

Catestatin can inhibit catecholamine release from chromaffin cells and adrenergic neurons. Catestatin can also have a strong vasodilator effect. This may be useful in understanding the pathophysiology of preeclampsia and its treatment. In this study, we investigated the serum catestatin levels in pregnant women with and without preeclampsia. Fifty consecutive women with mild preeclampsia, 50 consecutive women with severe preeclampsia, and 100 consecutive pregnant women with a gestational age-matched (±1 week) uncomplicated pregnancy were evaluated in a cross-sectional study. Mean serum catestatin was significantly increased in the preeclampsia group compared to the control group (290.7 ± 95.5 pg/mL vs. 182.8 ± 72.0 pg/mL). Mean serum catestatin was comparable in mild and severe preeclampsia groups (282.7 ± 97.9 pg/mL vs. 298.7 ± 93.4 pg/mL, p = .431). Serum catestatin levels had positive correlations with systolic and diastolic blood pressure, urea, uric acid, and creatinine. In conclusion, serum catestatin levels are increased in preeclamptic pregnancies compared to gestational age-matched controls.IMPACT STATEMENTWhat is already known on this subject? The role of autonomic nervous system dysregulation in the pathophysiology of preeclampsia is known. The most obvious part of this dysregulation is the sympathetic nervous system activation. The adrenal medulla is one of the locations of the sympathetic nervous system in the body.What do the results of this study add? Serum catestatin levels were found to be correlated with clinical and laboratory data of preeclampsia. This highlights the importance of chromaffin cell secretions in the adrenal medulla in preeclampsia.What are the implications of these findings for clinical practice and/or further research? This study will help understand the role of the adrenal medulla in the autonomic nervous system dysregulation in preeclampsia. Also, control of serum catestatin levels may support the treatment of hypertension in preeclampsia.


Assuntos
Cromogranina A/sangue , Fragmentos de Peptídeos/sangue , Pré-Eclâmpsia/sangue , Adulto , Pressão Sanguínea , Estudos de Casos e Controles , Creatinina/sangue , Estudos Transversais , Feminino , Idade Gestacional , Humanos , Gravidez , Ureia/sangue , Ácido Úrico/sangue
11.
Taiwan J Obstet Gynecol ; 60(5): 869-873, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34507663

RESUMO

OBJECTIVE: To evaluate the possible associations between serum Neprilysin (NEP) levels and preeclampsia and mild and severe preeclampsia subgroups. MATERIALS AND METHODS: Fifty-five consecutive women with mild preeclampsia and fifty-five consecutive women with severe preeclampsia were compared with 110 approximately gestational age-matched (±1 week) women with an uncomplicated pregnancy. RESULTS: Mean serum NEP was significantly higher in women with preeclampsia compared to that of the gestational age-matched-controls (231.62 ± 65.30 pg/mL vs. 187.75 ± 84.38 pg/mL, p < 0.001). Mean serum NEP was significantly higher in the mild preeclampsia group compared to its gestational age-matched control group (228.84 ± 67.26 pg/mL vs. 186.14 ± 85.09 pg/mL, p = 0.008); and in the severe preeclampsia group compared to its gestational age-matched control group (234.45 ± 63.85 pg/mL vs. 189.29 ± 84.59 pg/mL, p = 0.004). Serum NEP was positively correlated with systolic and diastolic blood pressure, BUN, uric acid, and creatinine. CONCLUSION: Mean serum NEP was significantly higher in women with preeclampsia than women with an uncomplicated pregnancy. Further studies are needed to elucidate the possible therapeutic role of NEP inhibitors to treat preeclampsia.


Assuntos
Neprilisina/sangue , Pré-Eclâmpsia/diagnóstico , Biomarcadores/sangue , Pressão Sanguínea , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Pré-Eclâmpsia/sangue , Gravidez , Adulto Jovem
12.
Hypertens Pregnancy ; 40(2): 144-151, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34014801

RESUMO

Objective: To evaluate the serum survivin level in preeclampsia.Methods: Eighty-eight pregnancies complicated with preeclampsia and 88 gestational-age (GA)-matched uncomplicated pregnancies were evaluated.Results: Mean serum survivin was detected to be significantly decreased in the early- (EOPE) and late-onset (LOPE) preeclampsia subgroups than the GA-matched control-groups; and were comparable in EOPE- and LOPE-groups after correction for GA. Serum survivin had weak negative correlations with systolic and diastolic arterial blood pressure.Conclusion: The serum survivin level was decreased in preeclamptic patients than the GA-matched controls. More comprehensive studies are needed to clarify the timing and extent of placental apoptosis in preeclampsia.


Assuntos
Pré-Eclâmpsia/diagnóstico , Survivina/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Idade Gestacional , Humanos , Pré-Eclâmpsia/sangue , Gravidez
13.
J Matern Fetal Neonatal Med ; 34(6): 943-947, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31146610

RESUMO

PURPOSE: To evaluate the possible associations between the single-layer locked- and unlocked-uterine closure technique and closure area biometry, and cesarean scar healing in recurrent cesarean section. MATERIAL AND METHODS: In this randomized prospective study, elective second cesarean section of 120 singleton pregnant women were randomized into the single-layer locked- and unlocked-continuous uterus closure technique. During the operation, the upper and lower edge thickness of the uterine incision were measured. In order to evaluate the healing in the cesarean scar area, all women were examined with vaginal ultrasonography 6-8 months after the cesarean section. The possible associations between locked- and unlocked-uterine closure technique and closure area biometry and cesarean scar healing were evaluated. RESULTS: After the drop-outs, a total of 86 women, 45 in the locked-continuous closure group and 41 in the unlocked-continuous closure group were evaluated. There was no statistically significant difference between the groups in terms of demographic and clinical parameters, such as perioperative uterine closure area biometry, need for additional suture, duration of operation and amount of bleeding. However, a significantly greater number of additional sutures for hemostasis was necessary in the unlocked-continuous compared to the locked-continuous closure group. The rate of cesarean scar defect (CSD) and residual myometrium thickness were comparable whereas the healing rate was significantly higher in the locked-continuous closure group compared to the unlocked-continuous closure group (0.71 ± 0.90 vs. 0.64 ± 0.10, p = .032). In women with CSD, the lower edge was 4 mm thinner than the women without CSD (10.48 ± 6.13 mm vs. 14.53 ± 7.13 mm, p = .006). Moreover, the thickness difference between the lower and upper edge was significantly greater if CSD was present compared to the absence of CSD (5.88 ± 4.04 mm vs. 3.70 ± 3.00 mm, p = .006). CONCLUSIONS: There was no association between CSD and locked versus unlocked suture technique used for the closure of uterine incision in the second cesarean section. The biometric evaluation of the scar area has shown that the thin lower wound edge and unevenness between the lower and the upper wound edges may play a role in incomplete healing of the uterine incision.


Assuntos
Cesárea , Histerotomia , Cesárea/efeitos adversos , Cicatriz/etiologia , Cicatriz/patologia , Feminino , Humanos , Gravidez , Estudos Prospectivos , Útero/diagnóstico por imagem , Útero/patologia , Útero/cirurgia , Cicatrização
14.
J Matern Fetal Neonatal Med ; 34(8): 1249-1254, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31195859

RESUMO

AIM: To evaluate the possible associations between creatine kinase (CK), cardiac troponin T (cTnT), N-terminal-pro-B-type natriuretic peptide (NT-proBNP), and s100B levels in umbilical cord blood and nonstress test results, cord-blood gas analyses and Apgar scores. MATERIAL AND METHODS: A total of 93 cesarean section deliveries after 34 + 0/7 gestational week (GW) were evaluated. The study (n = 50) and control (n = 43) groups consisted of type III and type I nonstress test (NST) according to the 2008 National Institute of Child Health and Human Development workshop report on electronic fetal monitoring. The serum levels of ProBNP II, S100-B, CK-MB, and cTnT were measured in cord blood and were evaluated according to the NST results, cord-blood gas analyses (pH and base-excess values) and 1- and 5-minute Apgar scores. Exclusion criteria for both groups included congenital abnormalities, multiple pregnancy, chorioamnionitis, oligohydramnios, polyhydramnios, intrauterine growth retardation (IUGR), and placental abruption. RESULTS: Mean age, weight, height, gestational age, and birth weight were comparable in type I and III NST groups. 1- and 5- minute Apgar, umbilical artery and vein pH values, and base deficiency were significantly lower in type III NST group compared to the type I NST group. The serum 100B (1616 ± 119 versus 533 ± 95 ng/L, p < .001), CK-MB (28.67 ± 21.17 versus 14.20 ± 11.26 ng/L, p < .001), cTnT (657 ± 396 versus 230 ± 132 ng/L, p < .001) and proBNP (1727 ± 379 versus 1069 ± 721 ng/L, p < .001) levels were significantly elevated in the NST type III compared to the NST type I group. The serum 100B, CK-MB, cTnT and proBNP levels were significantly elevated in the cord pH < 7.00 (n = 10) compared to pH = 7.00-7.15 group (n = 18). The serum 100B and proBNP were significantly elevated in the cord pH = 7.00-7.15 compared to the pH > 7.15 group (n = 65), whereas serum cTnT and proBNP levels were comparable in the latter two groups. In the study group, S100B, cTnT, and proBNP had negative correlations with 1- and 5-minute Apgar scores. All of the four markers showed negative correlations with A. umbilicalis pH and base excess. CONCLUSIONS: Mean S100B, CK-MB, cTnT, and NT-proBNP were significantly higher in the study group compared to the control group. The serum 100B, CK-MB, cTnT, and proBNP levels were significantly elevated in the cord pH < 7.00 compared to pH = 7.00-7.15 group. The serum 100B and proBNP were significantly elevated in the cord pH = 7.00-7.15 compared to the pH > 7.15 group.


Assuntos
Peptídeo Natriurético Encefálico , Troponina T , Biomarcadores , Cesárea , Criança , Creatina Quinase , Feminino , Sangue Fetal , Frequência Cardíaca Fetal , Humanos , Fragmentos de Peptídeos , Placenta , Gravidez , Subunidade beta da Proteína Ligante de Cálcio S100
15.
Surgery ; 169(2): 411-418, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32838986

RESUMO

BACKGROUND: Our current knowledge of diabetes mellitus in intraductal papillary mucinous neoplasm is very limited and its prevalence and predictive value for malignant transformation are not clear. This study sought to systematically review the literature to define the prevalence of diabetes mellitus in intraductal papillary mucinous neoplasm and to evaluate the association of diabetes mellitus with the progression to high-grade dysplasia or invasive cancer. METHODS: A PubMed/Medline systematic search was performed to identify studies reporting data on preoperative diabetes mellitus in intraductal papillary mucinous neoplasm. Articles meeting the predefined inclusion criteria were analyzed and a meta-analysis was performed. The study was preregistered (PROSPERO ID: CRD42020153581). RESULTS: From the initially detected 827 studies, 27 studies including resected patients with histologically confirmed intraductal papillary mucinous neoplasm were included. The global prevalence of preoperative diabetes mellitus was 25% (1,112 of 4,412); whereas new-onset/worsening diabetes mellitus was reported in 6% of patients (68 of 1,202). The meta-analysis revealed that patients with pre-existing diabetes mellitus had an increased risk of harboring a main pancreatic duct involvement (risk ratio 1.43, 95% confidence interval: 1.21-1.69, P < .001), high-grade dysplasia (risk ratio 1.27, 95% confidence interval: 1.01-1.59, P = .04), and invasive cancer (risk ratio 1.61, 95% confidence interval: 1.33-1.95, P < .001). CONCLUSION: The prevalence of diabetes mellitus in intraductal papillary mucinous neoplasm is high, and diabetic patients demonstrate an increased risk of a more aggressive disease. Therefore, diabetes mellitus should be increasingly considered in the stratification of patients with intraductal papillary mucinous neoplasm. Further investigations to determine the mechanisms behind the association with progression should be carried out.


Assuntos
Adenocarcinoma Mucinoso/epidemiologia , Carcinoma Ductal Pancreático/epidemiologia , Diabetes Mellitus/epidemiologia , Carga Global da Doença , Neoplasias Pancreáticas/epidemiologia , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/cirurgia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Diabetes Mellitus/diagnóstico , Progressão da Doença , Humanos , Pancreatectomia/estatística & dados numéricos , Ductos Pancreáticos/patologia , Ductos Pancreáticos/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/estatística & dados numéricos , Período Pré-Operatório , Prevalência , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco
16.
J Obstet Gynaecol ; 41(6): 927-932, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33064040

RESUMO

Considering the complex pathogenesis of endometriosis, which is associated with many cellular or molecular processes, such as proliferation, angiogenesis, inflammation, we evaluated the diagnostic value of a quadruple panel of serum markers CA125, endocan, YKL-40 and copeptin, for the prediction of endometriosis and moderate - severe endometriosis. Seventy women with endometriosis and 70 women without endometriosis were evaluated. Serum CA125, endocan, copeptin and YKL-40 levels were significantly increased in women with endometriosis compared to the women without endometriosis and in the minimal - mild endometriosis group compared to the no-endometriosis group. YKL-40, endocan and copeptin levels were significantly increased in the moderate - severe endometriosis group compared to the mild -moderate endometriosis group but the difference in CA125 levels remained non-significant. The quadruple panel score had an AUC of 0.954, a sensitivity of 96.5% and specificity of 84.6% for prediction of moderate - severe endometriosis. Zero or one positive marker had a sensitivity of 91.4% and specificity of 88.57% to rule out endometriosis. In conclusion, a quadruple panel of serum markers-CA125, endocan, YKL-40, and copeptin may be beneficial for the diagnosis of endometriosis and especially moderate - severe endometriosis. Further studies are needed to prove the efficacy of this panel.Impact statementWhat is already known on this subject? Many serum markers including CA125 have been investigated so far and suggested to be associated with endometriosis. However, none of these markers is sensitive and specific enough to diagnose endometriosis.What do the results of this study add? A quadruple panel score (CA125, endocan, YKL-4 and copeptin) had an AUC of 0.954, a sensitivity of 96.5% and specificity of 84.6% for prediction of moderate - severe endometriosis.What are the implications of these findings for clinical practice and/or further research? A high score may be beneficial to warn the surgeon about the risk of moderate to severe endometriosis if the patient will be operated anyway. A negative test of the quadruple panel may show high odds that there is no endometriosis which may prevent unnecessary surgery.


Assuntos
Antígeno Ca-125/sangue , Proteína 1 Semelhante à Quitinase-3/sangue , Endometriose/diagnóstico , Glicopeptídeos/sangue , Testes Hematológicos/estatística & dados numéricos , Proteínas de Membrana/sangue , Proteínas de Neoplasias/sangue , Proteoglicanas/sangue , Adolescente , Adulto , Área Sob a Curva , Bancos de Espécimes Biológicos , Biomarcadores/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Adulto Jovem
17.
J Exp Clin Cancer Res ; 39(1): 289, 2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33357230

RESUMO

BACKGROUND: Nerve-cancer interactions are increasingly recognized to be of paramount importance for the emergence and progression of pancreatic cancer (PCa). Here, we investigated the role of indirect cholinergic activation on PCa progression through inhibition of acetylcholinesterase (AChE) via clinically available AChE-inhibitors, i.e. physostigmine and pyridostigmine. METHODS: We applied immunohistochemistry, immunoblotting, MTT-viability, invasion, flow-cytometric-cell-cycle-assays, phospho-kinase arrays, multiplex ELISA and xenografted mice to assess the impact of AChE inhibition on PCa cell growth and invasiveness, and tumor-associated inflammation. Survival analyses were performed in a novel genetically-induced, surgically-resectable mouse model of PCa under adjuvant treatment with gemcitabine+/-physostigmine/pyridostigmine (n = 30 mice). Human PCa specimens (n = 39) were analyzed for the impact of cancer AChE expression on tumor stage and survival. RESULTS: We discovered a strong expression of AChE in cancer cells of human PCa specimens. Inhibition of this cancer-cell-intrinsic AChE via pyridostigmine and physostigmine, or administration of acetylcholine (ACh), diminished PCa cell viability and invasion in vitro and in vivo via suppression of pERK signaling, and reduced tumor-associated macrophage (TAM) infiltration and serum pro-inflammatory cytokine levels. In the novel genetically-induced, surgically-resectable PCa mouse model, adjuvant co-therapy with AChE blockers had no impact on survival. Accordingly, survival of resected PCa patients did not differ based on tumor AChE expression levels. Patients with higher-stage PCa also exhibited loss of the ACh-synthesizing enzyme, choline-acetyltransferase (ChAT), in their nerves. CONCLUSION: For future clinical trials of PCa, direct cholinergic stimulation of the muscarinic signaling, rather than indirect activation via AChE blockade, may be a more effective strategy.


Assuntos
Colina O-Acetiltransferase/metabolismo , Colinérgicos/farmacologia , Inflamação/prevenção & controle , Neoplasias Pancreáticas/tratamento farmacológico , Acetilcolina/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose , Ciclo Celular , Movimento Celular , Proliferação de Células , Feminino , Humanos , Inflamação/metabolismo , Inflamação/patologia , Masculino , Camundongos , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Pancreatology ; 20(8): 1770-1778, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33121847

RESUMO

OBJECTIVE: Postoperative pancreatic fistula/POPF is the most feared complication in pancreatic surgery. Although several systematic reviews investigated the impact of somatostatin analogues on POPF, no stratification was performed regarding type of pancreatic resection (pancreaticoduodenectomy/PD; distal pancreatectomy/DP) and different somatostatin analogues. METHODS: This study was planed according to the Preferred-Reporting-Items-for-Systematic -Review-and-Meta-Analysis/PRISMA-guidelines. After screening databases for randomized controlled trials/RCT, studies were stratified into pancreatic resection techniques and data were pooled in meta-analyses containing subgroups of octreotide, somatostatin, lanreotide, pasireotide and vapreotide. RESULTS: The meta-analysis of studies with a mixed cohort of patients after pancreatic resection revealed a protective effect of somatostatin analogues for morbidity (RR: 0.71, p < .00001) but not for mortality (RR: 1.07, = 0.78) or intra-abdominal abscesses (RR: 1.00, p = 1.00). Moreover, no effect was visible for mortality (RR: 1.57, p = .15), morbidity (RR: 0.87, p = .15) and intra-abdominal abscesses (RR: 0.92, p = .48) after PD. The meta-analysis of patients after PD revealed no impact of somatostatin analogues on POPF (RR: 0.87, p = .19) and clinically relevant POPF (RR: 0.69, p = .30). However, treatment with somatostatin analogues in the mixed cohort showed less POPF (RR: 0.60, p < .00001) and clinically relevant POPF (RR: 0.47, p = .02), which was also the case after DP (RR: 0.41, p = .03). CONCLUSION: Somatostatin analogues did not affect POPF and clinically relevant POPF after PD, but seemed to be associated with less POPF after DP. As no sufficiently powered RCT could be identified by the systematic review, further RCTs are urgently needed to investigate the effect of somatostatin analogues after DP. STUDY REGISTRATION: CRD42018099808.


Assuntos
Pâncreas , Pancreatectomia , Fístula Pancreática , Pancreaticoduodenectomia , Somatostatina , Anastomose Cirúrgica , Humanos , Morbidade , Pâncreas/cirurgia , Pancreatectomia/efeitos adversos , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Somatostatina/análogos & derivados
19.
J Perinat Med ; 49(1): 60-66, 2020 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-32866127

RESUMO

OBJECTIVES: To evaluate the serum levels of the serine proteinase inhibitor kallistatin in women with preeclampsia (PE). METHODS: The clinical and laboratory parameters of 55 consecutive women with early-onset PE (EOPE) and 55 consecutive women with late-onset PE (LOPE) were compared with 110 consecutive gestational age (GA)-matched (±1 week) pregnant women with an uncomplicated pregnancy and an appropriate for gestational age fetus. RESULTS: Mean serum kallistatin was significantly lower in women with PE compared to the GA-matched-controls (27.74±8.29 ng/mL vs. 37.86±20.64 ng/mL, p<0.001); in women with EOPE compared to that of women in the control group GA-matched for EOPE (24.85±6.65 ng/mL vs. 33.37±17.46 ng/mL, p=0.002); and in women with LOPE compared to that of women in the control group GA-matched for LOPE (30.87±8.81 ng/mL vs. 42.25±22.67 ng/mL, p=0.002). Mean serum kallistatin was significantly lower in women with EOPE compared to LOPE (24.85±6.65 ng/mL vs. 30.87±8.81 ng/mL, p<0.001). Serum kallistatin had negative correlations with systolic and diastolic blood pressure, creatinine, and positive correlation with GA at sampling and GA at birth. CONCLUSIONS: Serum kallistatin levels are decreased in preeclamptic pregnancies compared to the GA-matched-controls. This decrease was also significant in women with EOPE compared to LOPE. Serum kallistatin had negative correlation with systolic and diastolic blood pressure, creatinine and positive correlation with GA at sampling and GA at birth.


Assuntos
Pré-Eclâmpsia/sangue , Serpinas/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Gravidez , Adulto Jovem
20.
Eur J Obstet Gynecol Reprod Biol ; 250: 188-194, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32460227

RESUMO

OBJECTIVE: To evaluate whether bilateral common iliac artery (CIA) temporary clamping reduces blood loss during cesarean-hysterectomy of placenta percreta cases. STUDY DESIGN: A total of 32 women, who underwent cesarean-hysterectomy under bilateral CIA temporary clamping (n = 12) and without any arterial clamping or ligation (control group, n = 20) due to placenta percreta in Gaziantep University Hospital were retrospectively evaluated. The intra- and postoperative outcomes such as blood loss, blood transfusion and complications were compared between the two groups. RESULTS: Age, parity, body-mass-index and gestational-age were similar in the two groups. The estimated blood loss was lower in the temporary clamping of CIA group than the control group (595 ± 172 mL vs 1450 ± 662 mL, P < 0.001). The number of intraoperative packed-red-blood-cells (0.17 ± 0.58 units vs 1.85 ± 1.46 units, P = 0.002) and fresh-frozen-plasma (0.17 ± 0.58 units vs 1.7 ± 1.49 units, P = 0.005) transfusions were lower in the CIA temporary clamping group than the control group. The rate of women, who received blood/blood products were significantly lower in the CIA temporary clamping group compared to the control group (75 % vs 16 %, P = 0.001). Duration of operation was longer in the CIA temporary clamping group (140 ± 38 min vs 90 ± 25 min, p = 0.001). No complication or maternal death was encountered during this study. CONCLUSION: Bilateral CIA temporary clamping method reduces the intraoperative blood loss and the amount of intraoperative blood/blood product transfusions during cesarean-hysterectomy due to placenta percreta.


Assuntos
Placenta Acreta , Perda Sanguínea Cirúrgica/prevenção & controle , Constrição , Feminino , Humanos , Histerectomia/efeitos adversos , Artéria Ilíaca/cirurgia , Placenta Acreta/cirurgia , Gravidez , Estudos Retrospectivos
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