A. R. Dehpour, PharmD, PhD
A. Javadian, MD
Vol 56, No 6 (2018)
Multiple myeloma (MM) is clonal B-cell malignancy characterized by the progressive proliferation of malignant plasma cells and accumulation of monoclonal immunoglobulin (M-spike) in blood and urine. Pomalidomide is an immunomodulatory agent which has potentially suppressed myeloma cell progression, especially in drug-resistant cases. As epigenetic modifications have an important role in gene regulation and because of the revealing role of DNA-Methyltransferase 1 (DNMT1) overexpression in myeloma pathogenesis, in this study DNMT1, 3a and 3b genes expression of U266 myeloma cell line treated with pomalidomide have been evaluated. In this study after treatment of U266 cells with 1 μM pomalidomide for 48 hours, total RNA extraction and cDNA synthesis was performed. Gene expression of DNMT1, 3a and 3b has been evaluated using real time PCR technique. The result of this study show that pomalidomide can downregulate the expression of DNMT1, 3a, and 3b in 48 hours of treatment as 0.049, 0.058 and 0.055, respectively as comparing with untreated control (P<0.05). Based on these results we conclude that pomalidomide has desired effect on epigenetic modification by downregulation of DNMTs genes expression and has been considered as an effective drug for inhibition of myeloma proliferation.
It is established that cancer stem cells (CSCs) have potential in tumor formation, progression, and metastasis in different types of solid tumors. Additionally, recent studies have demonstrated that Genistein consumption is correlated with lowered cancer rate and metastasis decrease. In this study, we premised that Genistein could be an influential agent targeting breast cancer stem cell-like cells. In this survey, CD44+/CD24-cells (cancer stem cell-like cells) were isolated from MDA-MB-231 cells by magnet-activated cell sorting (MACS). The effect of various concentrations of Genistein on the cell proliferation and viability in MDA-MB-231 CD44+/CD24-cells tested in comparison to their parental cells utilizing MTT assay, invasion assay. The results of this study show that Genistein could inhibit invasion in MDA-MB-231 cells. Also, we observed that Genistein could be efficient for invasion inhibition in CD44+/CD24-cells. Considering the finding that Genistein could have desired effects on MDA-MB-231 as well as CD44+/CD24-cells, we demonstrated that Genistein could be an influential agent for treating malignant and invasive breast tumors.
Breast cancer is the most frequent malignancy among women worldwide including Iranian women. The different markers have already been investigated for predicting invasion and metastases which one of the most tempting ones is Chemokines. In fact, one of the well-known mediators in the breast cancer metastases is stromal cell-derived factor-1 (SDF-1) CXCR4 chemokine. The CXCR4 chemokine receptor is a G-protein-coupled receptor that selectively binds to SFD-1 (also known as CXCL12). It is obvious that this chemokine receptor plays a critical role in some biologic processes. Nevertheless, there is not enough study to confirm the CXCR4 clinical importance and also its exact prognostic worth in the breast cancer. We carried out this diagnostic study. Immunohistochemically on 70 paraffin blocks of invasive ductal breast carcinoma and adjacent normal tissue simultaneously to assess the expression of CXCR4. The correlation between the presence and intensity of expression of this marker with various clinicopathological factors including age, tumor size, lymph node involvement, stage, and grade are evaluated in all patients. Among the 70 cases, 64 cancer specimens (91.4%) showed CXCR4 expression. It is found out that there is a significant difference between the expression of CXCR4 and the histological grade and lymph node metastasis (P<0.001), but no correlation with other clinicopathologic parameters, such as age, tumor size, and the stage is identified. By considering the CXCR4 intensity, we came across a significant difference between the high expression and the size, stage, histological grade and lymph node metastasis (P<0.001). Breast cancer is the most common invasive tumor to afflict women through the world. According to our study, there is a significant relationship between the expression of CXCR4 and grade, lymph node metastasis in the breast cancer. Furthermore, there is a direct significant correlation between the intensity of expression with grade, stage, tumor size, and lymph node metastasis. Thus, it can be used as a predictor factor for the breast cancer.
Neutropenia is characterized by a decrease in circulating neutrophil counts and consequent infections. The present study was performed so as to describe the clinical and laboratory findings of patients with congenital neutropenia in northwestern Iran. The patients' records of 31 patients with congenital neutropenia out of 280 neutropenic patients who had been referred to Tabriz Children's Hospital during a 3-year period (2011-2014), were reviewed. Thirty-one cases (17 female and 14 male), with a mean age of 5.3 ± 5.7 years, were diagnosed to suffer from congenital neutropenia. The disorders associated with congenital neutropenia were combined immunodeficiency (8 cases), severe congenital neutropenia (6 cases), common variable immunodeficiency (4 cases), severe combined immunodeficiency (2 cases) and metabolic syndrome (1 case). The median age of the onset of disease was 26.2 ± 60.8 months. The most common clinical manifestations during the course of illness were otitis media (13 cases), pneumonia (12 cases), recurrent aphthous stomatitis, lymphadenopathy and gingivitis (11 cases). Four neutropenic patients died because of recurrent infections. Neutropenia may occur in the context of the primary immunodeficiency disorders. Unusual, persistent or severe infections always pose a speculation to search for an underlying immunodeficiency syndrome and neutropenia, so as to avoid further life-threatening complications as a result of any delay in diagnosis.
All stages of initiation and progression of atherosclerosis are associated with inflammatory responses. Heat shock proteins (HSP-70) can play an important role in the pathogenesis of atherosclerosis. Serum High-sensitivity C-reactive protein (hs-CRP) is significantly associated with the severity of coronary arteriosclerosis. Omega 3 fatty acids contribute to the primary and secondary prevention of cardiovascular disease (CVD). The purpose of the current study was to assess the effect of omega-3 on serum HSP-70 and HsCRP in patients with atherosclerosis. The current study was a randomized, placebo-controlled, double-blind parallel-group clinical trial, involving 42 male patients with coronary artery disease (CAD). The volunteers were randomly allocated into two groups to receive 4 g omega-3 (containing 720 mg EPA plus 480 mg DHA) supplements (n=21) or placebo (n=21) per day for 8 weeks. Fasting blood samples were taken at the beginning and end of the trial to quantify serum levels of HSP-70 and hsCRP concentrations. The result of the present study revealed that no significant difference was observed between two groups before and after the intervention in terms of serum levels of Cholesterol, Triglyceride, FBS, serum Insulin and homeostasis model of assessment-insulin resistance (HOMA-IR). The difference of HSP-70 between two groups was statistically significant (P=0.04). There was no significant difference between two groups for hsCRP. The study showed that taking omega-3 fatty acids can ameliorate serum HSP-70 as inflammatory parameters. The results suggest more investigation to assess the pathway omega-3 leads to lower incidence of CVD.
Congenital heart disorders (CHDs) encompass inborn defects of the heart compartments. Polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene have continuously been reported as a modulating factor for CHDs. In a case-control study, the association of A1298C polymorphism of MTHFR gene with ventricular septal defect (VSD) and Tetralogy of Fallot (TOF), two common forms of CHDs, in the children of southeastern Iran was investigated. The presence of A1298C polymorphism was investigated using tetra-ARMS-PCR method, and statistical processes were carried out applying SPSS software (V:19). Males in the control group formed 40% and 60% (including 46.74% in VSD and 13.26% in in TOF). Although the association between gender and CHDs was not statistically significant, males had a higher risk of VSD (OR=1.7, 95% CI; 0.9-3.1, P=0.08). Overall frequency of AA, AC ,and CC genotypes of A1298C polymorphism were 55%, 43%, and 2% in CHDs patients respectively; while respective ratios were 50%, 48% and 2% in the controls (P>0.05). Patients with VSD were more commonly identified with AC+CC genotypes (52.8%) compared to TOF cases (23%, P=0.01). In stratified regression analysis, heterozygote genotype showed a significant protection against TOF (OR=0.3, 95% CI; 0.1-0.8, P=0.01). Frequency of variant allele was obtained 31.58% in CHD patients and 33.8% in the controls (P>0.05). Moreover, frequency of variant (C) allele was 35.2% in VSD compared to 18.8% in TOF (P>0.05). A1298C polymorphism of MTHFR gene seems to exert a significant protective effect against TOF.
Using internet has a growing popularity, especially among students. The aim of this study was to determine the prevalence of internet addiction and its relationship with the level of self esteem and life satisfaction in students of lorestan university of medical sciences in Iran. A cross-sectional study, with applying stratified sampling and then multi-stage cluster sampling method was performed. The sample size was 160. Four questionnaires (Demographic characteristics, Internet Addiction Test (IAT) by Dr. Kimberly Young, Rosenberg's Self esteem Scale and Diener’s Life Satisfaction Scale) were used to collect data, the software spss 16 was used for data analysis. Prevalence of internet addiction was 10%, and this problem was more prevalent in male students (P˂0.05). Moreover, there was a significant and adverse relation between internet addiction score and self esteem score (P=0.015), and life satisfaction score (P=0.012). There was a significant and direct relationship between life satisfaction and self esteem (P=0.001). Young people should be encouraged to use the internet as a more useful and efficient tool and become aware of the internet and its harmful effects.
Doppler sonography has been used for evaluation of different fetal responses to various drugs on doppler blood flow patterns in fetal circulation that may indicate poor fetal prognosis. To assess the uterine and fetal doppler blood flow velocimetry changes in the management of asymptomatic preterm labor with vaginal progesterone tablet, it is found that using a vaginal tablet of progesterone affects uterine, umbilical and fetal middle cerebral arteries in the second and third trimesters of pregnancy. This prospective Case series (uncontrolled longitudinal study) was conducted in an outpatient clinic and emergency unit in Moheb Yas hospital during 2015-2016. For all subjects, 200 mg vaginal progesterone tablet (one tablet before bedtime) was administered. Additionally, transvaginal Doppler sonography was performed to measure uterus, umbilical, and middle cerebral arteries before the treatment with progesterone and 24 hours after the treatment with that, respectively. The mean gestational age of participants was 28.8±2.9 weeks, ranging from 23 to 32 weeks of gestation. There was no significant change in the fetal middle cerebral artery-peak systolic velocity (MCA-PSV), middle cerebral artery resistance index (MCA-RI), MCA-PI, Umbilical arterial Systolic-Diastolic (UA S/D), Right UtA-RI and Left UtA-RI before the beginning of progesterone treatment to 24 hours after. The current study indicated that the 200 mg vaginal tablet of progesterone for treatment of preterm labor leads to a reduction in the middle cerebral artery and the uterine artery PI and RI and an increase in umbilical artery S/D, respectively. Vaginal progesterone can improve fetoplacental perfusion in pregnancies complicated by preterm labor. This a preliminary result from a case series study and it has to be confirmed by a randomized clinical trial in future.
Laryngeal chondrosarcoma is a rare tumor that involves head and neck region such as larynx in rare cases. This malignant tumor usually grows quite slowly. The patient may experience symptoms for several years before a diagnosis is made. The diagnosis is achieved by clinical, radiological and pathological features. Management is basically surgical. Prognosis is generally good, depending basically on histologic grade. Herein, we report a case of laryngeal chondrosarcoma presented with hoarseness. Spiral CT scan demonstrated an expansile mass with calcification originating from cricoid cartilage. The patient underwent surgery for open excisional biopsy, and postoperative histopathologic evaluations confirmed "laryngeal chondrosarcoma" as definite diagnosis. The patient denied total laryngectomy for complete removal of the tumor. Six months follow up showed no more growth.
Cerebral venous thrombosis is an uncommon disorder in children however it can be associated with serious clinical consequences. As it is a rare condition without any specific clinical presentation, it is usually undiagnosed. Clinical manifestation of cerebral thrombosis in children is relatively different from adult because of age-related differences in the vascular and neurologic systems. We present a case of a twenty days boy with a history of one-week lethargy and poor feeding and grand mal seizure. He had hypernatremia and severe dehydration. Non-contrast CT scan of the brain revealed superior sagittal and both transverse and sigmoid sinus thrombosis. The patient was treated in neonatal ICU with a favorable clinical response. We also present a fourteen days girl who presented with three days of fever, poor feeding, tachycardia, respiratory distress, and grand mal seizure. She had hypernatremia and severe dehydration. Non-contrast CT scan of the brain revealed superior sagittal sinus thrombosis and right temporal lobe infarction. She was also treated in neonatal ICU with noticeable improvement in symptoms. These cases demonstrate the importance of dehydration in neonatal and clinical suspicion of cerebral venous thrombosis (CVT). We present these two cases to enhance the awareness of clinical practitioners. CVT is an unusual and serious condition in neonates and due to its nonspecific clinical presentation often remains unrecognized. Early neuroimaging, including transfontanel doppler ultra-sonography, and non-contrast CT scan in all neonates with neonatal seizures will improve detection.
We present the case of how a massive proximal deep vein thrombosis result of an unknown recurrence of a previously colonic malignancy treated, classically known Trousseau´s Syndrome, can mimic symptoms of severe peripheral arterial disease in a patient affected of peripheral chronic arterial disease surgically treated. Trousseau´s Syndrome is commonly associated with serious and chronic diseases and a variety of paraneoplastic thromboembolic disorders. Thrombotic episodes may precede the diagnosis of cancer and be the potential marker for an unknown and occult malignancy. We highlight the key points of the Trousseau´Syndrome and those paraneoplastic vasculopathies related that can mimic a vascular disease or complication.
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