Therapeutic approaches for targeting receptor tyrosine kinase like orphan receptor-1 in cancer cells

Introduction: There is a high expression of receptor tyrosine kinase like orphan receptor-1 (ROR-1), a tyrosine kinase receptor, in various tumor-cell types. ROR-1 is involved in many key processes in cancer including proliferation, survival and metastasis. Hence, ROR-1 is an attractive and promising therapeutic target. There are many therapeutic approaches that target ROR-1 and these include specific monoclonal antibodies (mAbs), modified T cells (CART cell), miRNAs and tyrosine kinase inhibitors (TKI).

Areas covered: This review examines ROR-1 structure and function, immunotherapeutic strategies including specific chimeric antigen receptor (CARs) T cells and miRNAs and other targeted approaches such as the use of tyrosine kinase inhibitors.

Expert opinion: Chimeric antibodies, CARs T cells, bi-specific T cell engagers (BiTEs), miRNAs and TKIs are used to target the ROR-1 marker on cancer cell lines. By selecting the most favorable therapeutic approaches regarding ROR-1 in vivo, anti-ROR-1 antibodies or CAR T cells can be also used for diagnosis of ROR-1⁺ cancer cells in new technologies such as biosensors. Moreover, ROR-1 targeted combination therapy with other cancer biomarkers could be considered a novel therapeutic strategy for cancer treatment.     

Flixweed vs. Polyethylene Glycol in the Treatment of Childhood Functional Constipation: A Randomized Clinical Trial

Background:

Polyethylene glycol (PEG) is often considered as the first-line treatment for functional constipation in children. Descurainia sophia (L.) Webb et Berth (D. sophia) is a safe recommended medicine in Iranian folk and Traditional Persian Medicine for the treatment of constipation.

Objectives:

To clinically compare D. sophia with PEG 4000 (without electrolyte) in pediatric constipation and to assess its efficacy and side effects.

Patients and Methods:

120 patients aged 2 - 12 years with constipation for at least 3 months were included in an 8 weeks lasting randomized controlled trial within two parallel-groups. Children received either PEG, 0.4 g/kg/day, or D. sophia seeds, 2 grams (for children aged 2 - 4 years) and 3 grams (for those aged > 4 years) per day.

Results:

A total of 109 patients completed the study (56 in D. sophia and 53 in PEG group). At the end of the study, 36 (64.3%) patients in D. sophia group and 29 (54.7%) in PEG group were out of Rome III criteria (P = 0.205). Median weekly stool frequency in 0, 1, 2, 3 weeks of the treatment was found to be 2, 5, 5, 5 in D. sophia and 3, 4, 4, 5 in PEG group (P = 0.139, 0.076, 0.844, 0.294), respectively. The number of patients who suffered flatulence was less (5, 8.9%) in D. sophia group as compared to PEG group (6, 11.3%) at the end of the trial (P = 0.461). D. sophia taste was less tolerated.

Conclusions:

D. sophia is introduced as a cheap and available medication which can be applied as a safe alternative to conventional PEG in the management of pediatric chronic functional constipation.     

Placental lesions associated with acute atherosis

Objective: Acute atherosis is a lesion of the spiral arteries characterized by fibrinoid necrosis of the vessel wall, an accumulation of fat-containing macrophages, and a mononuclear perivascular infiltrate, which can be found in patients with preeclampsia, fetal death, small-for-gestational age, spontaneous preterm labor/premature prelabor rupture of membrane, and spontaneous mid-trimester abortion. This lesion is thought to decrease blood flow to the intervillous space which may lead to other vascular lesions of the placenta. The objective of this study was to test whether there is an association between acute atherosis and placental lesions that are consistent with maternal vascular underperfusion (MVU), amniotic fluid infection (AFI), fetal vascular thrombo-occlusive disease (FVTOD) or chronic inflammation.

Material and methods: A retrospective cohort study of pregnant women who delivered between July 1998 and July 2014 at Hutzel Women’s Hospital/Detroit Medical Center was conducted examine 16?457 placentas. The frequency of placenta lesions (diagnosed using the criteria of the Perinatal Section of the Society for Pediatric Pathology) was compared between pregnancies with and without acute atherosis.

Results: Among 16?457 women who were enrolled, 10.2% (1671/16?457) were excluded, leaving 14?786 women who contributed data for analysis. Among them, the prevalence of acute atherosis was 2.2% (326/14?786). Women with acute atherosis were more than six times as likely as those without to have placental lesions consistent with maternal underperfusion (adjusted odds ratio – aOR: 6.7; 95% CI 5.2–8.6). To a lesser degree, acute atherosis was also associated with greater risks of having either lesions consistent with FVTOD (aOR 1.7; 95% CI 1.2–2.3) or chronic chorioamnionitis (aOR 1.9; 95% CI 1.3–3), but not with other chronic inflammatory lesions, after adjusting for gestational age at delivery. In contrast, women with acute atherosis were 60% less likely to have lesions consistent with AFI, adjusting for gestational age at delivery (aOR 0.4; 95% CI 0.3–0.5).

Conclusions: Acute atherosis is associated with increased risks of having placental lesions consistent with MVU, and to a lesser extent, chronic chorioamnionitis and those consistent with FVTOD.     

An Investigation of the Effects of Curcumin on Anxiety and Depression in Obese Individuals: A Randomized Controlled Trial

Objective: To investigate the effectiveness of curcumin, a natural polyphenolic compound with antioxidant and anti-inflammatory activities, on the frequency of symptoms of anxiety and depression in obese individuals. Methods: In this double blind, cross-over trial, 30 obese subjects were randomized to receive either curcumin (1 g/day) or placebo for a period of 30 days. Following a wash-out interval of 2 weeks, each subject was crossed over to the alternative regimen for a further 30 days. Severity of anxiety and depression was assessed at baseline and at weeks 4, 6 and 10 of the trial using the Beck Anxiety Inventory (BAI) and Beck Depression Inventory (BDI) scales, respectively. Results: Mean BAI score was found to be significantly reduced following curcumin therapy (P=0.03). However, curcumin supplementation did not exert any significant impact on BDI scores (P=0.7). Conclusion: Curcumin has a potential anti-anxiety effect in individuals with obesity.     

Functional constipation in children:non-pharmacological approach

Teb(medicine)as described by Avicenna on the opening pages of the al-Qānūn fīal-Tibb(The Cannon of Medicine)was"a science by which one learns the conditions of the human body in health and in the nonexistence of health to keep health or to bring it back".According to Avicenna’s Canon of Medicine and other traditional Persian medicine(TPM)resources,the observance of the six essential qualities provides guidance to any medical intervention.     

Observations on cattle schistosomiasis in the Sudan, a study in comparative medicine. V. The effect of praziquantel therapy on naturally acquired resistance to Schistosoma bovis

Studies in the White Nile area of the Sudan have shown that Zebu cattle acquire a high degree of resistance to Schistosoma bovis as a result of repeated natural exposures without, however, being able to eliminate their populations of adult schistosomes, although these do show greatly suppressed fecundity. To test whether these adult worms are necessary for the maintenance of resistance we cured six "naturally resistant" cattle (TC group) with a double treatment of 25 mg/kg praziquantel and compared their response to a 70,000 cercariae challenge with groups of "naturally resistant" but untreated cattle (UC group) and with previously unexposed, challenged cattle (CC group). Challenge was carried out 7 weeks after the second dose of praziquantel. The results confirmed that untreated cattle are "naturally resistant" and also showed that resistance was not abrogated by cure of the naturally-acquired infections. Thus, fecal egg counts after challenge reached mean maxima of 2,432 eggs per gram (epg) in the CC, but only 5 epg and 28 epg in the TC and UC groups, respectively. Similarly, mean worm counts were 85% and 69% lower in the TC and UC groups, respectively, and mean tissue egg densities were reduced by 72-99%, and 56-80%. Histopathologically, the TC and UC groups were also far less affected than the CC. Effective praziquantel treatment does therefore not destroy naturally acquired resistance to S. bovis, and may benefit infected livestock even in the absence of transmission control. The situation in human schistosomiasis is less clear, but there are several epidemiological and experimental indications of a similar conclusion for S. mansoni.     

2D Statistical Lung Shape Analysis Using Chest Radiographs: Modelling and Segmentation

Journal of Digital Imaging - Accurate information of the lung shape analysis and its anatomical variations is very noticeable in medical imaging. The normal variations of the lung shape can be...