Anti-cancer effect of metformin on the metastasis and invasion of primary breast cancer cells through mediating NF-kB activity

Current evidence strongly suggests that aberrant activation of the nuclear factor kappa B (NF-kB) signaling cascade is connected to carcinogenesis. The matrix metalloproteinases (MMP) which are also the key agents for tumor metastasis may be potent candidates for tumor diagnosis in clinics. In this in vitro study, we hypothesized that metformin with an effective dose can inhibit tumor cell proliferation and metastasis by modulating the expressions of MMP-2 and -9 and interfering with NF-kB signaling in primary breast cancer cells (PBCCs). 300 000 cells per ml were obtained from biopsies of breast tumors from five human donors. The cell viability and proliferation were tested. Immunocytochemistry was performed for MMP-2, MMP-9, and NF-kB, and enzyme-linked immunosorbent assay for NF-kB activity, quantitative real-time PCR for RELA/p65, IkBα, MMP-2, and MMP-9. Three different doses of metformin (5, 10, and 25 mM) (Met) reduced the viability and proliferation of PBCCs in a dose-dependent manner, maximum inhibition was observed at 25 mM Met. The expression of RELA/p65 was not affected by 25 mM Met. Nuclear immunoreactivity and activity of NF-kB reduced while cytoplasmic NF-kB (p65) elevated by 25 mM Met compared to non-treatment (P < 0.05). The expression and immunoreactivity of MMP-9 but not MMP-2 were decreased by 25 mM Met treatment, compared with the non-treatment (P < 0.05). Metformin may have an essential antitumor role in the invasion and metastasis pathways of PBCCs by downregulating the MMP-9 expression blocking both the activity and nuclear translocation of NF-kB.     

Single-Center Study of 72 Patients with Severe Combined Immunodeficiency: Clinical and Laboratory Features and Outcomes

Journal of Clinical Immunology - Severe combined immunodeficiency is an inborn error of immunity characterized by impairments in the numbers and functions of T and B lymphocytes due to various...     

Monogenic lupus due to DNASE1L3 deficiency in a pediatric patient with urticarial rash,hypocomplementemia, pulmonary hemorrhage,and immune-complex glomerulonephritis

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease and usually involves the skin, musculoskeletal system, and kidneys. More than 30 genes have been to monogenic lupus, so far. Monogenic lupus is often characterized by an early-onset, similar family history, and syndromic appearance. Herein we present a pediatric patient with DNASE1L3 deficiency, suffering from both urticarial skin lesions, recurrent hemoptysis, and renal involvement, eventually diagnosed as this rare monogenic lupus.The patient suffered from recurrent urticarial rash and hemoptysis since the age of 15 months of age. He had microscopic hematuria, mild proteinuria, hypocomplementemia, and positive antinuclear antibody, anti-dsDNA, and antineutrophil cytoplasmic antibodies. Renal biopsy yielded immunocomplex glomerulonephritis. Due to early-onset, similar sibling history and consanguineous parents, we suspected monogenic lupus and performed whole-exome sequencing, which further revealed a homozygous T97Ifs*2 mutation (NM_004944.4: c.290_291delCA/p.Thr97Ilefs*2) in DNASE1L3 gene.In conclusion, DNASE1L3 deficiency should be thought when juvenile SLE occurs with early disease-onset, pulmonary hemorrhage, glomerulonephritis, and recurrent urticarial rash along with ANCA positivity.     

Assessment of ischemia-modified albumin level in patients with recurrent pregnancy loss during the first trimester

Objective

The finding that ischemia-modified albumin (IMA) is increased in pre-eclamptic pregnancy suggests a role for IMA as a potential biomarker for abnormal placental development related to miscarriage. This study was undertaken to evaluate IMA levels in women with recurrent pregnancy loss (RPL).

Study design

This case-control study was performed between March 2008 and September 2009, at the Department of Obstetrics and Gynecology of Meram School of Medicine. Serum IMA and albumin concentrations were assessed in 43 women with a history of two or more unexplained first trimester miscarriages (group 1), and 42 healthy pregnant women (group 2) in the first trimester. IMA, adjusted IMA and albumin concentrations were compared between the groups. Statistical analysis was performed using Student's t-test and Mann-Whitney U test.

Results

IMA and adjusted IMA levels were significantly higher in women with RPL (1.11 + 0.08 and 1.09 + 0.09, respectively) compared to women in group 2 (0.88 + 0.10 and 0.88 + 0.11, respectively). Albumin levels in group 1 were significantly lower compared with group 2. There was a negative correlation between IMAand albumin levels in each group.

Conclusion

Maternal IMA levels appear to be elevated in women with early RPL. This finding may suggest that an abnormally high hypoxic intrauterine environment may be associated with abnormal placental development that contributes to early miscarriage.     

Pandemic influenza H1N1 2009 virus infection in pregnancy in Turkey

ObjectivesTo describe the clinical characteristics of the pregnant women who were hospitalized in a tertiary referral hospital with pandemic influenza H1N1 2009 virus infection and neonatal outcomes from October 2009 to December 2009 during which the pandemic influenza cases peaked in Turkey.Materials and MethodsTwenty-five pregnant women who were hospitalized with influenza-like illness and who had laboratory confirmation for pandemic influenza H1N1 virus infection were evaluated prospectively.ResultsOf the 25 patients, 4 (16%) were in the first trimester, 8 (32%) were in the second trimester, and 13 (52%) were in the third trimester. The median time from the onset of symptoms to the initiation of antiviral therapy was 1 day (range 1–9 days). Nineteen (76%) patients received oseltamivir treatment. It took 1.6 days on the average for the fever defervescence after the initiation of treatment or hospitalization. Of the 14 patients who underwent chest radiography, three had findings consistent with pneumonia. The mean duration of hospitalization was 4.8 days. Four women (16%) were admitted to an intensive care unit, but there were no maternal or neonatal deaths in this series. At the time of their H1N1 hospitalization, seven women delivered by cesarean at 33–40 weeks gestation, two vaginally at 38 weeks gestation, and two had an abortion at 10 weeks and 16 weeks of gestation, respectively. None of the infants had any evidence of influenza infection.ConclusionPregnant women are at increased risk for complications from pandemic influenza H1N1 virus infection. Timely medical attention with early recourse to antiviral therapy is associated with a better outcome in H1N1-affected pregnant women.     

The value of urocortin and Ca-125 in the diagnosis of endometrioma

Purposes

In this study, we sought to establish the value of a new molecule, urocortin (Ucn), in the diagnosis of endometrioma and compare with Ca-125 to identify superiority of urocortin.

Methods

Of the patients operated on at our hospital with the initial diagnosis of adnexal mass, 88 patients whose pathology results were endometrioma and benign ovarian cyst were included in the study. As a result of the pathological examination, the patients were assessed in two groups. Group 1 consisted of 42 cases of endometrioma and Group 2 included 46 cases of benign ovarian cyst (control group). The serum Ucn and CA 125 levels of patients were measured from the blood samples drawn prior to the operation.

Results

While the serum Ucn level was 4.8?±?1.00?ng/ml in the endometrioma group, it was 4.5?±?1.03?ng/ml in the control group (P?=?0.21). The difference was statistically not meaningful. On the other hand, mean serum Ca-125 level was 43.8?U/l (11.7?C251) in the endometrioma group, it was 16.5?U/l (4.3?C121.1) in the control group. The difference was statistically meaningful (P?=?0.001). When the cut-off point for Serum Ca-125 level was taken as 21.38, sensitivity and specificity levels were found to be 88.1 and 63%. When the cut-off point for Ucn was taken as 4.16, sensitivity was 76.2%, and specificity 45.7%.

Conclusion

Ucn was not found to be efficient in distinguishing endometrioma from other benign ovarian cysts or to be superior to CA125 in the diagnosis of endometrioma.     

Vascular endothelial growth factor +405 C/G polymorphism is highly associated with an increased risk of endometriosis in Turkish women

Objective  

Endometriosis is a chronic gynecological disease characterized by the growth of hormonally responsive, endometrial tissue outside the uterine cavity. The present study aims to analyze two vascular endothelial growth factor (VEGF) polymorphisms (−460 C/T and +405 C/G) in Turkish women with and without endometriosis.     

Role of the Neutrophil-Lymphocyte Ratio in the Differential Diagnosis of Exudative Pleural Effusion

OBJECTIVES:Pleural effusion is a common diagnostic and clinical problem. The differential diagnosis of pleural effusion may be difficult and may require several procedures, including invasive ones. Certain studies have investigated biochemical parameters to facilitate the diagnosis of exudative pleural effusion; however, it remains a challenging problem in clinical practice. We aimed to investigate the potential role of the neutrophil-lymphocyte ratio, which can be easily obtained by determining the cell count of the pleural fluid, in the differential diagnosis of exudative pleural effusion.METHODS:Records from patients who underwent thoracentesis and pleural fluid analysis between May 1, 2013, and March 1, 2015, were obtained from the electronic database of our hospital. The patients who met the inclusion criteria were divided into five groups according to their diagnosis: malignant pleural effusion, para-malignant pleural effusion, para-pneumonic effusion, tuberculosis-related effusion or other. The neutrophil-lymphocyte ratio value was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. The patient groups were compared according to the given parameter.RESULTS:A total of 465 patients who met the inclusion criteria among 1616 patients with exudative pleural effusion were included in the study. The mean neutrophil-lymphocyte ratio value was significantly lower in tuberculosis-related pleural effusion compared to malignant, para-pneumonic and para-malignant effusions (p=0.001, p=0.001, p=0.012, respectively). The areas under the curve for tuberculosis pleurisy compared to malignant, para-pneumonic and para-malignant effusions were 0.38, 0.36, and 0.37, respectively. Lower cut-off values had higher sensitivity but lower specificity for tuberculosis pleurisy, while higher cut-off values had higher specificity but lower sensitivity for this condition.CONCLUSION:The pleural fluid neutrophil-lymphocyte ratio, which is an inexpensive, reproducible, and easily calculated hematological parameter, may facilitate the differential diagnosis of pleural effusion.     

Genotype–phenotype correlations in individuals with pathogenic RERE variants

Heterozygous variants in the arginine‐glutamic acid dipeptide repeats gene (RERE) have been shown to cause neurodevelopmental disorder with or without anomalies of the brain, eye, or heart (NEDBEH). Here, we report nine individuals with NEDBEH who carry partial deletions or deleterious sequence variants in RERE. These variants were found to be de novo in all cases in which parental samples were available. An analysis of data from individuals with NEDBEH suggests that point mutations affecting the Atrophin‐1 domain of RERE are associated with an increased risk of structural eye defects, congenital heart defects, renal anomalies, and sensorineural hearing loss when compared with loss‐of‐function variants that are likely to lead to haploinsufficiency. A high percentage of RERE pathogenic variants affect a histidine‐rich region in the Atrophin‐1 domain. We have also identified a recurrent two‐amino‐acid duplication in this region that is associated with the development of a CHARGE syndrome‐like phenotype. We conclude that mutations affecting RERE result in a spectrum of clinical phenotypes. Genotype–phenotype correlations exist and can be used to guide medical decision making. Consideration should also be given to screening for RERE variants in individuals who fulfill diagnostic criteria for CHARGE syndrome but do not carry pathogenic variants in CHD7.     

Contribution of DOG1 expression to the diagnosis of gastrointestinal stromal tumors

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract, and the majority contain KIT or PDGFRA-activating mutations. However, up to 10% of GISTs are c-kit-negative. Antibodies with increased sensitivity and specificity for the detection of c-kit-negative GIST cases may be of value, especially because some of these cases may also benefit from tyrosine kinase inhibitor therapy.