Myeloid cells are recruited to damaged tissues where they can resolve infections and tumor growth or stimulate wound healing and tumor progression. Recruitment of these cells is regulated by integrins, a family of adhesion receptors that includes integrin CD11b. Here we report that, unexpectedly, integrin CD11b does not regulate myeloid cell recruitment to tumors but instead controls myeloid cell polarization and tumor growth. CD11b activation promotes pro-inflammatory macrophage polarization by stimulating expression of microRNA Let7a. In contrast, inhibition of CD11b prevents Let7a expression and induces cMyc expression, leading to immune suppressive macrophage polarization, vascular maturation, and accelerated tumor growth. Pharmacological activation of CD11b with a small molecule agonist, Leukadherin 1 (LA1), promotes pro-inflammatory macrophage polarization and suppresses tumor growth in animal models of murine and human cancer. These studies identify CD11b as negative regulator of immune suppression and a target for cancer immune therapy.

The Ras-like GTPases RalA and B are important drivers of tumor growth and metastasis1. Chemicals that block Ral function would be valuable as research tools and for cancer therapeutics. Here, we used protein structure analysis and virtual screening to identify drug-like molecules that bind a site on the GDP-form of Ral. Compounds RBC6, RBC8 and RBC10 inhibited Ral binding to its effector RalBP1, Ral-mediated cell spreading in murine fibroblasts and anchorage-independent growth of human cancer cell lines. Binding of RBC8 derivative BQU57 to RalB was confirmed by isothermal titration calorimetry, surface plasma resonance and 15N-HSQC NMR. RBC8 and BQU57 show selectivity for Ral relative to Ras or Rho and inhibit xenograft tumor growth similar to depletion of Ral by siRNA. Our results show the utility of structure-based discovery for development of therapeutics for Ral-dependent cancers.

Osteopontin (OPN) is a chemokine like phosphorylated glycoprotein that plays important role in cancer progression. Extensive research from various laboratories has demonstrated the likely role of OPN in regulating the cell signaling that ultimately controls tumor growth and metastasis. Several earlier reports indicated that OPN is associated with various cancers; but its functional role in carcinogenesis is still not well defined. Besides the role of OPN in tumor biology, several studies have demonstrated the pathophysiological role of OPN in diverse biological events. This review will focus on recent advances in understanding the molecular mechanism by which OPN regulates a series of signaling cascades through activation of various kinases and transcription factors that ultimately control the expression of downstream effector genes, which contribute to tumor progression and angiogenesis in vitro and animal models. We will also provide evidences that suggest the enhanced expression of OPN is not only associated with several tumor types, but its level of expression is directly correlated to various stages of the clinical specimens of breast and prostate cancers. These studies may be useful for identifying novel OPN-based therapeutic approach for the treatment of cancer.

BackgroundBreast cancer is one of the most frequently diagnosed cancer and accounts for over 400,000 deaths each year worldwide. It causes premature death in women, despite progress in early detection, treatment, and advances in understanding the molecular basis of the disease. Therefore, it is important to understand the in depth mechanism of tumor progression and develop new strategies for the treatment of breast cancer. Thus, this study is aimed at gaining an insight into the molecular mechanism by which osteopontin (OPN), a member of SIBLING (Small Integrin Binding LIgand N-linked Glycoprotein) family of protein regulates tumor progression through activation of various transcription factors and expression of their downstream effector gene(s) in breast cancer.ResultsIn this study, we report that purified native OPN induces ICAM-1 expression in breast cancer cells. The data revealed that OPN induces NF-κB activation and NF-κB dependent ICAM-1 expression. We also observed that OPN-induced NF-κB further controls AP-1 transactivation, suggesting that there is cross talk between NF-κB and AP-1 which is unidirectional towards AP-1 that in turn regulates ICAM-1 expression in these cells. We also delineated the role of mTOR and p70S6 kinase in OPN-induced ICAM-1 expression. The study suggests that inhibition of mTOR by rapamycin augments whereas overexpression of mTOR/p70S6 kinase inhibits OPN-induced ICAM-1 expression. Moreover, overexpression of mTOR inhibits OPN-induced NF-κB and AP-1-DNA binding and transcriptional activity. However, rapamycin further enhanced these OPN-induced effects. We also report that OPN induces p70S6 kinase phosphorylation at Thr-421/Ser-424, but not at Thr-389 or Ser-371 and mTOR phosphorylation at Ser-2448. Overexpression of mTOR has no effect in regulation of OPN-induced phosphorylation of p70S6 kinase at Thr-421/Ser-424. Inhibition of mTOR by rapamycin attenuates Ser-371 phosphorylation but does not have any effect on Thr-389 and Thr-421/Ser-424 phosphorylation of p70S6 kinase. However, OPN-induced phosphorylation of p70S6 kinase at Thr-421/Ser-424 is being controlled by MEK/ERK pathway.ConclusionThese results suggest that blocking of OPN-induced ICAM-1 expression through mTOR/p70S6 kinase signaling pathway may be an important therapeutic strategy for the treatment of breast cancer.

BackgroundComplementary and alternative medicine (CAM) use is popular in former Soviet Central Asian countries including Mongolia. However, no studies are available on CAM use among patients with cancer in countries of this region. The aim of this research is to describe the prevalence and patterns of CAM use by patients with cancer in Mongolia.MethodsA cross-sectional study was conducted using data from 482 cancer patients attending the National Cancer Center in Mongolia from September 2015 to February 2016. The survey instrument included 25 questions regarding CAM used, factors associated with use of CAM, cancer-related characteristics, and participants’ socio-demographic profile.ResultsAmong 482 respondents (response rate, 95.6%), 47.9% reported using one or more CAM modalities. Products of animal origin were the most popular modalities of CAM, followed by herbal products. Half of the users used CAM while receiving conventional treatment of cancer. Among users, only 29% discussed the CAM use with their doctors. Female gender, younger age, higher education, shorter disease duration, and prior use of CAM were significantly associated with CAM use.ConclusionsCAM appears to be widely accepted by patients with cancer in Mongolia. The findings support the urgent need for further in-depth study into commonly used oral CAM products and their potential effects on health of patients with cancer in Mongolia. High prevalence of CAM use among cancer patients in our study warrants further studies in other countries of Central Asia.

BackgroundHerbal medicines in pregnancy are increasingly used worldwide with prevalence of up to 67%. Although this popularity is mainly because of the common belief that these medicines are safe, recent reports suggest that several herbal medicines are potentially harmful to mother and fetus if used in pregnancy.MethodsThis cross-sectional study was conducted in July and August of year 2017, at maternity wards of two public hospitals in Dhaka, Bangladesh. Postpartum women were interviewed via the structured questionnaire to collect information regarding socio-demographic and health characteristics, patterns of herbal medicines used in the previous pregnancy, and outcome of pregnancy.ResultsTwo hundred forty-three postpartum women participated in the study, with 70% of them using at least one modality of herbal medicines in previous pregnancy. Ginger, black seed, lemon tea, prune, and mustard oil were most commonly used herbal medicines. Herbal medicines were mostly used for pregnancy-related symptoms such as nausea, vomiting, and cold. Fifteen (8.8%) herbal medicine users reported side effects.ConclusionsThis study highlights popularity of herbal medicines during pregnancy in Bangladesh. Previous herbal medicine users and unemployed women turned significantly more to herbal medicines during pregnancy. Reports of side effects and use of some potentially harmful modalities warrant awareness regarding proper use of herbal medicines in pregnancy and its pharmacovigilance.Electronic supplementary materialThe online version of this article (10.1186/s12906-018-2399-y) contains supplementary material, which is available to authorized users.

A better understanding of the signalling mechanism by which osteopontin promotes tumourigenesis may be useful in crafting novel osteopontin -based anticancer therapy. The role of osteopontin in promoting cancer progression is the subject of in depth investigation and thus targeting osteopontin might be a suitable therapeutic approach for the treatment of cancer.

BackgroundDue to the lack of strong evidence on safety and efficacy of complementary and alternative medicine (CAM) approaches, the use of CAM in women during pregnancy could be hazardous for mother and fetus. Meanwhile, little is known regarding the patterns, the reasons and the factors affecting use of CAM among pregnant women in Iraq.MethodsA cross sectional survey design was used to carry out face-to-face interviews with 335 consecutive pregnant women. The questionnaire comprised of three sections: socio-demographic characteristics, pregnancy-related aspects and the patterns and attitudes towards use of CAM. Determinants of CAM use were assessed through the logistic regression analysis.ResultsThree hundred thirty-five pregnant women completed the questionnaire. 56.7 % reported using at least one form of CAM modalities. In total, 24 different types of CAM were used; with herbal medicine (53.7 %) and multivitamins (36.3 %) the most commonly used modalities. From the logistic regression analysis, the variables positively associated with CAM use were: rural residence (odds ratio (OR) 2.0, p < 0.01), no occupation (OR 2.7, p < 0.05), high income (OR 2.0, p < 0.05), perceived healthy status (OR 2.6, p < 0.05) and ever use of contraception (OR 2.0, p < 0.01). Only 0.5 % of CAM users disclosed their CAM use to physicians.ConclusionsThe proportion of CAM users among pregnant women is relatively high and it is important to learn what types of CAM they use. However, disclosure of CAM use was extraordinarily low. Given the low rate of disclosure, it should be ensured that physicians establish good level of communication with pregnant women and have adequate knowledge of CAM.