CD20-targeting in B-cell malignancies: novel prospects for antibodies and combination therapies

Expression of CD20 antigen by the most of transformed B cells is believed to be the driving force for targeting this molecule by using anti-CD20 monoclonal antibodies. While it is true that most lymphoma/leukemia patients can be cured, these regimens are limited by the emergence of treatment resistance. Based on these observations, development of anti-CD20 monoclonal antibodies and combination therapies have been recently proposed, in particular with the aim to optimize the cytotoxic activity. Here we outline a range of new experimental agents concerning the CD20 positive B-cell tumors which provide high benefit from conventional therapy.     

Did the GJB2 35delG mutation originate in Iran?

Mutations in GJB2 are a major cause of autosomal recessive non-syndromic hearing loss (ARNSHL) in many populations. A single mutation of this gene (35delG) accounts for approximately 70% of GJB2 mutations that are associated with ARNSHL in Caucasians in many European countries and also in Iranian. In this study, we used PCR and restriction digestion to genotype five single nucleotide polymorphisms (SNPs) that define the genetic background of the 35delG mutation over an interval of 98 Kbp that includes the coding and flanking regions of GJB2. Two microsatellite markers, D13S175 and D13S141, were also analyzed in patients and controls. These data suggest that the 35delG mutation originated in northern Iran.     

Evaluation of an anal sac adenocarcinoma tumor in a Spitz dog

A 9-year-old emasculated male Spitz with tenesmus and constipation had a subcutaneous mass at the left ventral aspect of the anus with history of polyuria and polydipsia. A complete blood cell count, serum biochemistry panel, and urinalysis (cystocentesis sample) were evaluated. Abnormalities in the serum biochemistry panel included a mildly elevated serum cholesterol concentration (7.28 mmol/L; reference interval, 2.70–5.94 mmol/L), increased serum alkaline phosphatase activity (184 U/L; reference interval, 9–90 U/L), alanine transaminase (122 U/L; reference interval, 5–60 U/L) activity and aspartate aminotransferase (80 U/L; reference interval, 5–55 U/L) activity, severe increased total calcium concentration (16.3 mg/dL; reference interval, 8.2–12.4 mg/dL or 9.3–11.4 mg/dL), and decreased total calcium concentration (3.4 mg/dL, reference interval, 2.5–5.6mg/dL). Furthermore, testing revealed an increased intact parathyroid hormone concentration (38.6 pmol/L; reference interval, 3–17 pmol/L). On cytologic and histopathologic examinations, various types of cells were observed. Most of the cells were oval to polygonal and had elliptical or elongate nuclei and a moderate amount of pale to basophilic cytoplasm. The remaining cells had round to oval nuclei and pale to basophilic cytoplasm. Cells of both types were loosely adhered to each other and were arranged in rosette-like structures. Both neoplastic cell types had fine homogenous chromatin and either a small indistinct nucleolus or no visible nucleolus. Mild anisokaryosis and anisocytosis were observed. Histologically, the mass consists of glandular structures formed by cuboidal cells admixed with bundles of spindle cells. Based on location and histologic features, the final diagnosis was adenocarcinoma of the apocrine gland of the anal sac, which should be included as a cytologic differential diagnosis when spindle cells and typical epithelial cells are observed in masses in the region of the anal sac of dogs.     

Steroid-depleted polycystic ovarian syndrome serum promotes in vitro oocyte maturation and embryo development

In vitro maturation (IVM) of immature oocytes obtained from patients with polycystic ovarian syndrome (PCOS) is considered as a novel strategy in order to reduce clinical side effects and cost of in vitro fertilization (IVF) technique. The aim of this study was to evaluate the effects of PCOS whole and steroid-depleted serums on in vitro oocyte maturation indices. Patients with PCOS were selected according to the Rotterdam criteria. Cumulus–oocyte complexes and blood serums were collected and pooled. Cumulus cells and immature oocytes were treated with 10% whole or steroid-depleted serums. Stearoyl-CoA desaturase-1 (SCD1) and cyclooxygenase-2 (COX2) expression levels in cumulus cells were evaluated by quantitative PCR. Fatty acid composition of cumulus cells was analyzed using gas–liquid chromatography. Polar body observation was considered as the oocyte maturation index. Oleate (1.28-fold, p?=?.006), SCD1 expression (450-fold, p?=?.001), and COX2 expression (35-fold, p?=?.02) in cumulus cell, as well as oocyte maturation (p?in vitro embryo development (p?相似文献   

Real life management of chronic urticaria: Multicenter and cross sectional study on patients and dermatologists in Iran

Recently, advances in understanding the etiology of urticaria and updates of diagnostic and therapeutic management guidelines have drawn attention to chronic urticaria (CU) morbidity. The present study aimed to evaluate Iranian dermatologists' practice and real life management of CU patients. A total of 35 dermatologists and 443 patients were included in the study. Number of female patients was 321 (72.5%). Mean (standard deviation) age of the study patients was 38 (13) years and the median (inter quartile range) of disease duration was 12 (6–48) months. Severity of patients' symptoms was mild for 32.1%, moderate for 38.7%, severe for 18.8%, and 10.4% of them had no evident signs or symptoms. The most common diagnostic methods were physical examination (96.6%), differential blood count (83.5%), erythrocyte sedimentation rate (77.4%), and C‐reactive protein (62.8%). The number of dermatologists prescribed nonsedating antihistamines (nsAH) in regular dose and high dose mono therapy were 26 (74%) and 6 (17%), respectively. About 66% of dermatologists were familiar with British Association of Dermatologists (BAD) guideline. The most common first‐line treatment for CU by Iranian dermatologists was nonsedating antihistamines in regular or high doses. The real‐life management of patients with CU in Iran was in accordance with the available practice guidelines.     

Molecular homogeneity in diverse geographical populations of Phlebotomus papatasi (Diptera, Psychodidae) inferred from ND4 mtDNA and ITS2 rDNA Epidemiological consequences.

An intraspecific study on Phlebotomus papatasi, the main proven vector of Leishmania major among the members of the subgenus Phlebotomus, was performed. The internal transcribed spacer 2 (ITS 2) of rDNA and the ND4 gene of mt DNA were sequenced from 26 populations from 18 countries (Albania, Algeria, Cyprus, Egypt, Greece, India, Iran, Israel, Italy, Lebanon, Morocco, Saudi Arabia, Spain, Syria, Tunisia, Turkey, Yugoslavia and Yemen), and compared. Samples also included three other species belonging to the subgenus Phlebotomus: P. duboscqi, a proven vector of L. major in the south of Sahara (three populations from Burkina Faso, Kenya and Senegal), P. bergeroti, a suspected vector of L. major (three populations from Oman Sultanate, Iran and Egypt), and one population of P. salehi from Iran. A phylogenetic study was carried out on the subgenus Phlebotomus. Our results confirm the validity of the morphologically characterized taxa. The position of P. salehi is doubtful. Variability in P. papatasi contrasts with that observed within other species having a wide distribution like P. (Paraphlebotomus) sergenti in the Old World or Lutzomyia (Lutzomyia) longipalpis in the New World. Consequently, it could be hypothesized that all populations of P. papatasi over its distribution area have similar vectorial capacities. The limits of the distribution area of L. major are correlated with the distribution of common rodents acting as hosts of the parasites.     

Effects of saffron (Crocus sativus L.) and its active constituent, crocin, on recognition and spatial memory after chronic cerebral hypoperfusion in rats

Cerebral ischemia produces brain damage and related behavioral deficits such as memory. In this study, a rat model of chronic cerebral hypoperfusion was used to determine whether saffron extract and crocin, which are potent antioxidants and free radical scavengers, can reduce vascular cognitive impairment. Male adult Wistar rats were administered different doses of an aqueous solution of crocin or hydroalcohol extract of saffron intraperitoneally (i.p.) 5 days after permanent occlusion of the common carotid arteries. Spatial learning and memory were assessed in training trials, 7–11 days after common carotid artery ligation using the Morris water maze. The results showed that the escape latency time was significantly reduced from 24.64 s in the control group to 8.77 and 10.47 s by crocin (25 mg/kg) and saffron extract (250 mg/kg). The traveled distance to find the platform was also changed from 772 cm in the control group to 251 and 294 cm in the crocin (25 mg/kg) and saffron extract (250 mg/kg) groups. The percentages of time spent in the target quadrant, in comparison with the control group (24.16%), increased to 34.25% in the crocin (25 mg/kg) and 34.85% in the saffron extract (250 mg/kg) group. This study suggests that saffron extract and crocin improve spatial cognitive abilities following chronic cerebral hypoperfusion and that these effects may be related to the antioxidant effects of these compounds. Copyright © 2011 John Wiley & Sons, Ltd.     

The Central Role for Microenvironment in B-Cell Malignancies: Recent Insights into Synergistic Effects of its Therapeutic Targeting and Anti-CD20 Antibodies

Most B-cell-related disorders can be cured with conventional agents; however, relapse is common, creating a need for additional therapeutic options. In agreement, recent biomarker studies corroborate the role played by functional crosstalk between malignant B cells and microenvironment which have added texture to clinical outcome. Here we outline the essential role of the tumor-associated niche in B-cell Lymphoma/Leukemia pathogenesis, in an attempt to optimize the use of microenvironment-targeted drugs and anti-CD20 antibodies in the various subsets.     

A review of anti-inflammatory,antioxidant, and immunomodulatory effects of Allium cepa and its main constituents

ContextAllium cepa L. (Liliaceae), known as onion, is consumed throughout the world. Onion and its derivatives including saponins, aglycones, quercetin, cepaenes, flavonoids, organosulfurs, and phenolic compounds, showed various pharmacological properties and therapeutic effects.ObjectiveAnti-inflammatory, antioxidant, and immunomodulatory effects of A. cepa and its main constituents, along with the underlying molecular mechanisms are presented.MethodsDatabases including, Web of Knowledge, Medline/PubMed, Scopus, and Google Scholar were checked for articles published between 1996 and the end of July 2020, using the key-words Allium cepa, quercetin, anti-inflammatory, antioxidant and immunomodulatory.ResultsA. cepa and its constituents mainly quercetin showed anti-inflammatory effects mediated via reduction of total and differential WBC counts, inhibition of chemotaxis of polymorphonuclear leukocytes, COX, and LOX pathways and prevented formation of leukotrienes and thromboxanes, prostaglandin E2 (PGE2) as onVCAM-1, NF-κB, MARK,d STAT-1, JNK, p38 and osteoclastogenesis. A. cepa and its derivatives showed antioxidant effect by decreasing lipid peroxidation, NAD(P)H, MDA, NO, LPO and eNOS but enhancing antioxidants such as SOD, CAT, GSH, GPx, GSPO, TrxR, SDH, GST and GR activities and thiol level. Immunomodulatory effects of the plant and quercetin was also shown by reduction of Th2 cytokines, IL-4, IL-5, and IL-13 as well as IL-6, IL-8, IL-10, IL-1β and TNF-α and IgE levels, but increased CD4 cells, IFN-γ level and IFN-γ/IL4 ratio (Th1/Th2 balance).ConclusionsThe effect of onion and its constituents on oxidative stress, inflammatory and immune system were shown indicating their therapeutic value in treatment of various diseases associated with oxidative stress, inflammation, and immune-dysregulation.