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Pharmacological Research: the Official Journal of the Italian Pharmacological Society

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https://www.readbyqxmd.com/read/28342790/lipocalin-2-and-iron-trafficking-in-the-tumor-microenvironment
#1
REVIEW
Michaela Jung, Christina Mertens, Rebekka Bauer, Claudia Rehwald, Bernhard Brüne
Iron is an essential element for virtually all organisms. It facilitates cell proliferation and growth but also contributes to major hallmarks of cancer such as tumor initiation, growth, and metastasis. Often, iron handling of tumor cells is disturbed, with altered iron acquisition, efflux, and storage. Targeting perturbed iron metabolic pathways might open opportunities towards novel approaches in cancer treatment. It is becoming clear that cells of the tumor microenvironment such as macrophages contribute to tumor progression...
March 22, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28336373/gender-differences-in-liver-disease-and-the-drug-dose-gender-gap
#2
REVIEW
Elena Buzzetti, Pathik M Parikh, Alessio Gerussi, Emmanuel Tsochatzis
Although gender-based medicine is a relatively recent concept, it is now emerging as an important field of research, supported by the finding that many diseases manifest differently in men and women and therefore, might require a different treatment. Sex-related differences regarding the epidemiology, progression and treatment strategies of certain liver diseases have long been known, but most of the epidemiological and clinical trials still report results only about one sex, with consequent different rate of response and adverse reactions to treatment between men and women in clinical practice...
March 20, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28336372/doxorubicin-targets-multiple-players-a-new-view-of-an-old-problem
#3
REVIEW
Donato Cappetta, Francesca Rossi, Elena Piegari, Federico Quaini, Liberato Berrino, Konrad Urbanek, Antonella De Angelis
Anthracycline cardiotoxicity remains a serious problem in paediatric and adult cancer survivors, and the advancement of cardio-oncology is a necessary step for an effective care of the patients that experience adverse cardiovascular effects. In this review, we discuss the multiple instruments used by clinicians that constitute the current strategies for primary and secondary prevention aiming at contrasting the onset of early and late doxorubicin-induced cardiotoxic events. The importance of early detection of cardiotoxicity and the following pharmacological therapy has been acknowledged with the emphasis put on impaired diastolic function, an increasingly recognized precocious sign of doxorubicin cardiotoxicity with an emerging scientific and clinical interest...
March 20, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28336371/novel-adaptive-and-innate-immunity-targets-in-hypertension
#4
REVIEW
Justine M Abais-Battad, John Henry Dasinger, Daniel J Fehrenbach, David L Mattson
Hypertension is a worldwide epidemic and global health concern as it is a major risk factor for the development of cardiovascular diseases. A relationship between the immune system and its contributing role to the pathogenesis of hypertension has been long established, but substantial advancements within the last few years have dissected specific causal molecular mechanisms. This review will briefly examine these recent studies exploring the involvement of either innate or adaptive immunity pathways. Such pathways to be discussed include innate immunity factors such as antigen presenting cells and pattern recognition receptors, adaptive immune elements including T and B lymphocytes, and more specifically, the emerging role of T regulatory cells, as well as the potential of cytokines and chemokines to serve as signaling messengers connecting innate and adaptive immunity...
March 20, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28336370/purinergic-p2y6-receptors-a-new-therapeutic-target-of-age-dependent-hypertension
#5
REVIEW
Caroline Sunggip, Akiyuki Nishimura, Kakeru Shimoda, Takuro Numaga-Tomita, Makoto Tsuda, Motohiro Nishida
Aging has a remarkable effect on cardiovascular homeostasis and it is known as the major non-modifiable risk factor in the development of hypertension. Medications targeting sympathetic nerve system and/or renin-angiotensin-aldosterone system are widely accepted as a powerful therapeutic strategy to improve hypertension, although the control rates remain unsatisfactory especially in the elder patients with hypertension. Purinergic receptors, activated by adenine, uridine nucleotides and nucleotide sugars, play pivotal roles in many biological processes, including platelet aggregation, neurotransmission and hormone release, and regulation of cardiovascular contractility...
March 20, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28330785/the-interplay-between-angiotensin-ii-tlr4-and-hypertension
#6
REVIEW
Vinicia Campana Biancardi, Gisele Facholi Bomfim, Wagner Luis Reis, Sarah Al-Gassimi, Kenia Pedrosa Nunes
Hypertension is a multifactorial disease. Although a number of different underlying mechanisms have been learned from the various experimental models of the disease, hypertension still poses challenges for treatment. Angiotensin II plays an unquestionable role in blood pressure regulation acting through central and peripheral mechanisms. During hypertension, dysregulation of the Renin-Angiotensin System is associated with increased expression of pro-inflammatory cytokines and reactive oxygen species causing kidney damage, endothelial dysfunction, and increase in sympathetic activity, among other damages, eventually leading to decline in organ function...
March 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28330784/vascular-endothelial-growth-factor-vegf-and-vegf-receptor-inhibitors-in-the-treatment-of-renal-cell-carcinomas
#7
REVIEW
Robert Roskoski
One Von Hippel-Lindau (VHL) tumor suppressor gene is lost in most renal cell carcinomas while the nondeleted allele exhibits hypermethylation-induced inactivation or inactivating somatic mutations. As a result of these genetic modifications, there is an increased production of VEGF-A and pro-angiogenic growth factors in this disorder. The important role of angiogenesis in the pathogenesis of renal cell carcinomas and other tumors has focused the attention of investigators on the biology of VEGFs and VEGFR1-3 and to the development of inhibitors of the intricate and multifaceted angiogenic pathways...
March 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28330783/influence-of-mdr1-cyp3a5-genetic-polymorphisms-on-trough-levels-and-therapeutic-response-of-imatinib-in-newly-diagnosed-patients-with-chronic-myeloid-leukemia
#8
Natarajan Harivenkatesh, Lalit Kumar, Sameer Bakhshi, Atul Sharma, Madhulika Kabra, Tirumurthy Velpandian, Ajay Gogia, Shivaram S Shastri, Nihar Ranjan Biswas, Yogendra Kumar Gupta
Polymorphisms in genes coding for imatinib transporters and metabolizing enzymes may affect imatinib pharmacokinetics and clinical response. Aim of this study was to assess the influence of polymorphisms in MDR1 and CYP3A5 genes on imatinib trough levels, cytogenetic and molecular response in patients with CML. Newly diagnosed patients with chronic-phase CML started on imatinib therapy were enrolled and followed up prospectively for 24 months. The following single nucleotide polymorphisms were genotyped; C1236T, C3435T, G2677T/A in MDR1 gene and A6986G in CYP3A5 gene...
March 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28323141/mechanistic-and-pharmacologic-insights-on-immune-checkpoint-inhibitors
#9
REVIEW
Randy F Sweis, Jason J Luke
The concept of augmenting the immune system to eradicate cancer dates back at least a century. A major resurgence in cancer immunotherapy has occurred over the past decade since the identification and targeting of negative regulators with antibody therapies to augment the anti-tumor immune response. Unprecedented responses across a broad array of cancer types elevated this class of therapies to the forefront of cancer treatment. The most successful drugs to date target the cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) pathways...
March 18, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28315429/vinpocetine-reduces-diclofenac-induced-acute-kidney-injury-through-inhibition-of-oxidative-stress-apoptosis-cytokine-production-and-nf-%C3%AE%C2%BAb-activation-in-mice
#10
Victor Fattori, Sergio M Borghi, Carla F S Guazelli, Andressa C Giroldo, Jefferson Crespigio, Allan J C Bussmann, Letícia Coelho-Silva, Natasha G Ludwig, Tânia L Mazzuco, Rubia Casagrande, Waldiceu A Verri
Acute kidney injury (AKI) represents a complex clinical condition associated with significant morbidity and mortality. Approximately, 19-33% AKI episodes in hospitalized patients are related to drug-induced nephrotoxicity. Although, considered safe, non-steroidal anti-inflammatory drugs such as diclofenac have received special attention in the past years due to the potential risk of renal damage. Vinpocetine is a nootropic drug known to have anti-inflammatory properties. In this study, we investigated the effect and mechanisms of vinpocetine in a model of diclofenac-induced AKI...
March 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28315428/p53-modulates-the-effect-of-ribosomal-protein-s6-kinase1-s6k1-on-cisplatin-toxicity-in-chronic-myeloid-leukemia-cells
#11
Ling-Yi Xiao, Wai-Ming Kan
Chronic myeloid leukemia (CML) is characterized by the expression of the oncoprotein, BCR-ABL. BCR-ABL inhibitors revolutionized CML chemotherapy while blast crisis (BC) CML patients are less responsive. Since suppression of ribosomal protein S6 kinase1 (S6K1) phosphorylation reverses the resistance to BCR-ABL inhibitor in CML cells and S6K1 inhibitors augment cisplatin toxicity in lung cancer cells, we speculated that combination of S6K1 inhibitor and cisplatin may be beneficial for eliminating BC CML cells...
March 14, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28302577/methamphetamine-effects-on-the-brain-gut-and-immune-system
#12
REVIEW
Monica D Prakash, Kathy Tangalakis, Juliana Antonipillai, Lily Stojanovska, Kulmira Nurgali, Vasso Apostolopoulos
Methamphetamine (METH) is a powerful central nervous system stimulant which elevates mood, alertness, energy levels and concentration in the short-term. However, chronic use and/or at higher doses METH use often results in psychosis, depression, delusions and violent behavior. METH was formerly used to treat conditions such as obesity and attention deficit hyperactivity disorder, but now is primarily used recreationally. Its addictive nature has led to METH abuse becoming a global problem. At a cellular level, METH exerts a myriad of effects on the central and peripheral nervous systems, immune system and the gastrointestinal system...
March 13, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28300617/sex-and-gender-related-prevalence-cardiovascular-risk-and-therapeutic-approach-in-metabolic-syndrome-a-review-of-the-literature
#13
REVIEW
Giacomo Pucci, Riccardo Alcidi, Lisanne Tap, Francesca Battista, Francesco Mattace-Raso, Giuseppe Schillaci
Metabolic syndrome (MS), a cluster of metabolic abnormalities linked to insulin-resistance and abdominal obesity, is associated with an increased risk of Type II diabetes mellitus (DM) and cardiovascular (CV) disease. Its prevalence is high, affecting 20% to 30% of the general population, and increases with age in a sex-specific manner: in fact, while below 50 years it is slightly higher in men, it reverses after 50 years. The pronounced age-related increase in the prevalence of MS in women occurs as the result of several factors, which may be classified into sex- and gender-related factors...
March 11, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28300616/does-gender-specific-risk-of-cardiovascular-events-in-type-2-diabetic-patients-depend-on-the-type-of-treatment-the-question-remains-open
#14
LETTER
Ilaria Campesi, Flavia Franconi, Giuseppe Seghieri, Marco Meloni
No abstract text is available yet for this article.
March 11, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28288941/differential-activation-of-pregnane-x-receptor-by-carnosic-acid-carnosol-ursolic-acid-and-rosmarinic-acid
#15
Chun Ling Seow, Aik Jiang Lau
Pregnane X receptor (PXR) regulates the expression of many genes, including those involved in drug metabolism and transport, and has been linked to various diseases, including inflammatory bowel disease. In the present study, we determined whether carnosic acid and other chemicals in rosemary extract (carnosol, ursolic acid, and rosmarinic acid) are PXR activators. As assessed in dual-luciferase reporter gene assays, carnosic acid, carnosol, and ursolic acid, but not rosmarinic acid, activated human PXR (hPXR) and mouse PXR (mPXR), whereas carnosol and ursolic acid, but not carnosic acid or rosmarinic acid, activated rat PXR (rPXR)...
March 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28288940/anti-inflammatory-mechanism-of-lonchocarpine-in-lps-or-poly-i-c-induced-neuroinflammation
#16
Yeon-Hui Jeong, Jin-Sun Park, Dong-Hyun Kim, Jihee Lee Kang, Hee-Sun Kim
Neuroinflammation plays an important role in the progression of various neurodegenerative diseases. In this study, we investigated the anti-inflammatory effects of lonchocarpine, a natural compound isolated from Abrus precatorius, under in vitro and in vivo neuroinflammatory conditions induced by challenge with lipopolysaccharide (LPS)- or polyinosinic-polycytidylic acid (poly(I:C)). Lonchocarpine suppressed the expression of iNOS and proinflammatory cytokines in LPS or poly(I:C)-stimulated BV2 microglial cells...
March 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28288939/breast-cancer-resistance-protein-bcrp-abcg2-and-p-glycoprotein-p-gp-abcb1-transport-afatinib-and-restrict-its-oral-availability-and-brain-accumulation
#17
Stéphanie van Hoppe, Rolf W Sparidans, Els Wagenaar, Jos H Beijnen, Alfred H Schinkel
Afatinib is a highly selective, irreversible inhibitor of EGFR and (HER)-2. It is orally administered for the treatment of patients with EGFR mutation-positive types of metastatic NSCLC. We investigated whether afatinib is a substrate for the multidrug efflux transporters ABCB1 and ABCG2 and whether these transporters influence oral availability and brain and other tissue accumulation of afatinib. We used in vitro transport assays to assess human (h)ABCB1-, hABCG2- or murine (m)Abcg2-mediated transport of afatinib...
March 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28286251/treatment-of-type-2-diabetes-mellitus-patients-with-insulin-possible-lowering-of-protective-effect-of-female-gender-on-the-cardiovascular-outcomes
#18
LETTER
Mykola Khalangot, Victor Kravchenko
No abstract text is available yet for this article.
March 10, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28286134/berberine-bioisostere-q8-compound-stimulates-osteoblast-differentiation-and-function-in-vitro
#19
Younho Han, Yifeng Jin, Sung Ho Lee, Daulat Bikram Khadka, Won-Jea Cho, Kwang Youl Lee
The Q8 compound is a unique derivative of berberine. The present study investigated the functional role of Q8 to evaluate its potential for use in bone regeneration, especially in osteoblast differentiation. The safe concentration of Q8 increased BMP4-induced alkaline phosphatase (ALP) activity, and induced RNA expression of ALP, bone sialoprotein (BSP), and osteocalcin (OC). The activities of ALP-, BSP- and OC-luciferase reporters were also increased by Q8. During osteoblast differentiation, Q8 stabilized the Runx2 and Osterix protein abundance by blocking the ubiquitin-proteasome pathway, which in turn promoted Runx2 and Osterix induced transcriptional activity and subsequently increased the osteoblast differentiation...
March 7, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28279813/the-role-of-chemokines-in-hypertension-and-consequent-target-organ-damage
#20
REVIEW
Nathan P Rudemiller, Steven D Crowley
Immune cells infiltrate the kidney, vasculature, and central nervous system during hypertension, consequently amplifying tissue damage and/or blood pressure elevation. Mononuclear cell motility depends partly on chemokines, which are small cytokines that guide cells through an increasing concentration gradient via ligation of their receptors. Tissue expression of several chemokines is elevated in clinical and experimental hypertension. Likewise, immune cells have enhanced chemokine receptor expression during hypertension, driving immune cell infiltration and inappropriate inflammation in cardiovascular control centers...
March 6, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
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