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Tyrosine kinase inhibitors and pregnancy

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https://www.readbyqxmd.com/read/27920724/insulin-induces-relaxation-and-decreases-hydrogen-peroxide-induced-vasoconstriction-in-human-placental-vascular-bed-in-a-mechanism-mediated-by-calcium-activated-potassium-channels-and-l-arginine-nitric-oxide-pathways
#1
Lissette Cabrera, Andrea Saavedra, Susana Rojas, Marcela Cid, Cristina Valenzuela, David Gallegos, Pamela Careaga, Emerita Basualto, Astrid Haensgen, Eduardo Peña, Coralia Rivas, Juan Carlos Vera, Victoria Gallardo, Leandro Zúñiga, Carlos Escudero, Luis Sobrevia, Mark Wareing, Marcelo González
HIGHLIGHTS Short-term incubation with insulin increases the L-arginine transport in HUVECs.Short-term incubation with insulin increases the NO synthesis in HUVECs.Insulin induces relaxation in human placental vascular bed.Insulin attenuates the constriction induced by hydrogen peroxide in human placenta.The relaxation induced by insulin is dependent on BKCa channels activity in human placenta. Insulin induces relaxation in umbilical veins, increasing the expression of human amino acid transporter 1 (hCAT-1) and nitric oxide synthesis (NO) in human umbilical vein endothelial cells (HUVECs)...
2016: Frontiers in Physiology
https://www.readbyqxmd.com/read/27919989/teratogenic-effect-of-radotinib-case-report
#2
Juyoung Cheon, Jung Whan Ahn, Kyung Min Park, Guisera Lee, Yun Sung Jo
BACKGROUND: Simultaneous presentation of pregnancy and chronic myeloid leukemia (CML) is rare. Tyrosine kinase inhibitors (TKIs) are rarely used in pregnancy. There is almost no information on the effect of recently developed TKIs on the fetus. CASE REPORT: A 22-year-old woman became pregnant while using radotinib, a novel TKI for CML. She was concerned about the possible teratogenic effect of radotinib; hence the first pregnancy was terminated. The patient underwent full-term delivery at the second pregnancy...
December 2016: Anticancer Research
https://www.readbyqxmd.com/read/27856999/simvastatin-alleviates-pathology-in-a-rat-model-of-preeclampsia-involving-erk-mapk-pathway
#3
Xiujuan Dong, Dandan Shi
Preeclampsia (PE) is a pregnancy-specific condition characterized by new-onset hypertension. There is evidence suggesting that imbalances of angiogenic factors, oxidative stress, and inflammation may be central to the pathogenesis of PE. We sought to investigate whether simvastatin would reduce mean arterial pressure, restore the angiogenic balance, and ameliorate inflammation and oxidative stress in a nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME)-induced rat model of PE. We found that blood pressure was significantly increased in the l-NAME group compared to normal pregnant dams (P < ...
November 16, 2016: Reproductive Sciences
https://www.readbyqxmd.com/read/27698065/fluid-shear-stress-promotes-placental-growth-factor-upregulation-in-human-syncytiotrophoblast-through-the-camp-pka-signaling-pathway
#4
Edouard Lecarpentier, Anthony Atallah, Jean Guibourdenche, Marylise Hebert-Schuster, Sarah Vieillefosse, Audrey Chissey, Bassam Haddad, Guillaume Pidoux, Daniele Evain-Brion, Abdul Barakat, Thierry Fournier, Vassilis Tsatsaris
The effects of fluid shear stress (FSS) on the human syncytiotrophoblast and its biological functions have never been studied. During pregnancy, the syncytiotrophoblast is the main source of placental growth factor (PlGF), a proangiogenic factor involved in the placental angiogenesis and the vascular adaptation to pregnancy. The role of FSS in regulating PlGF expression in syncytiotrophoblasts is unknown. We investigated the impact of FSS on the production and secretion of the PlGF by the human syncytiotrophoblasts in primary cell culture...
October 3, 2016: Hypertension
https://www.readbyqxmd.com/read/27550925/original-research-featured-article-imatinib-mesylate-gleevec-inhibits-notch-and-c-myc-signaling-five-day-treatment-permanently-rescues-mammary-development
#5
Robert Callahan, Barry A Chestnut, Ahmed Raafat
Wap-Int3 transgenic females expressing the Notch4 intracellular domain (designated Int3) from the whey acidic protein promoter exhibit two phenotypes in the mammary gland: blockage of lobuloalveolar development and lactation, and tumor development with 100% penetrance. Previously, we have shown that treatment of Wap-Int3 tumor bearing mice with Imatinib mesylate (Gleevec) is associated with complete regression of the tumor. In the present study, we show that treatment of Wap-Int3 mice during day 1 through day 6 of pregnancy with Gleevec leads to the restoration of their lobuloalveolar development and ability to lactate in subsequent pregnancies in absence of Gleevec treatment...
January 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/27389567/pregnancy-part-of-life-in-chronic-myelogenous-leukemia
#6
Arjun Datt Law, Dennis Dong Hwan Kim, Jeffrey Howard Lipton
Management of pregnant patients with chronic myelogenous leukemia (CML) is challenging. Some of the factors that need to be considered include stage of pregnancy, disease status, and degree of drug exposure. Managing a patient who has been diagnosed while pregnant requires a different approach as compared with a patient who becomes pregnant while on the treatment with a tyrosine kinase inhibitor (TKI). Younger patients may wish to conceive while on treatment and need a more personalized treatment plan based on the degree and duration of their molecular status...
July 7, 2016: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/27376810/role-of-axl-in-preeclamptic-epcs-functions
#7
Ying Hu, Xiao-Ping Liu, Xiao-Xia Liu, Yan-Fang Zheng, Wei-Fang Liu, Ming-Lian Luo, Hui Gao, Ying Zhao, Li Zou
Axl encodes the tyrosine-protein kinase receptor, participating in the proliferation and migration of many cells. This study examined the role of Axl in functions of endothelial progenitor cells (EPCs). Axl was detected by RT-PCR and Western blotting in both placentas and EPCs from normal pregnancy and preeclampsia patients. The Axl inhibitor, BMS777-607, was used to inhibit the Axl signalling pathway in EPCs. Cell proliferation, differentiation, migration and adhesion were measured by CCK-8 assay, cell differentiation assay, Transwell assay, and cell adhesion assay, respectively...
June 2016: Journal of Huazhong University of Science and Technology. Medical Sciences
https://www.readbyqxmd.com/read/27352939/management-of-pregnant-chronic-myeloid%C3%A2-leukemia-patients
#8
Elisabetta Abruzzese, Malgorzata Monika Trawinska, Paolo de Fabritiis, Michele Baccarani
INTRODUCTION: Since the introduction of tyrosine kinase inhibitors (TKIs) therapy, chronic myeloid leukemia (CML), has moved from a fatal illness to a manageable disease with a possible normal lifespan. For this reason is more and more frequent that younger patients address the possibility to conceive, if men, or get pregnant, if women. Knowledge of safety and risks concerning both patient and progeny, as well as important cultural, ethical and psychosocial issues must be taken into consideration...
August 2016: Expert Review of Hematology
https://www.readbyqxmd.com/read/27334856/clinical-features-and-treatment-outcomes-of-51-patients-with-chronic-myeloid-leukemia-treated-with-a-tyrosine-kinase-inhibitor-at-a-single-institution-from-2002-to-2014
#9
Noriaki Kawano, Shuro Yoshida, Sayaka Kawano, Takuro Kuriyama, Kiyoshi Yamashita, Hidenobu Ochiai, Kazuya Shimoda, Fumihiko Ishikawa, Akira Ueda, Ikuo Kikuchi
Although clinical trials of first- and second-generation tyrosine kinase inhibitors (TKIs) have been shown to improve the prognosis of chronic myeloid leukemia (CML), there is still uncertainty about the clinical features, treatment outcomes, adverse effects, and other possible problems of their use in the clinical setting. We retrospectively analyzed 51 CML patients treated with TKIs at a single institution between 2002 and 2014. The patients (median age: 53.8 years) were classified as having chronic (n = 48), accelerated (n = 2), or blastic phase (n = 1) CML...
2016: Journal of Clinical and Experimental Hematopathology: JCEH
https://www.readbyqxmd.com/read/27280428/restoring-placental-growth-factor-soluble-fms-like-tyrosine-kinase-1-balance-reverses-vascular-hyper-reactivity-and-hypertension-in-pregnancy
#10
Minglin Zhu, Zongli Ren, José S Possomato-Vieira, Raouf A Khalil
Preeclampsia (PE) is a pregnancy-related hypertensive disorder (HTN-Preg) with unclear mechanism. An imbalance between antiangiogenic soluble fms-like tyrosine kinase-1 (sFlt-1) and angiogenic placental growth factor (PlGF) has been observed in PE, but the vascular targets and signaling pathways involved are unclear. We assessed the extent of sFlt-1/PlGF imbalance and vascular dysfunction in a rat model of HTN-Preg produced by reduction of uteroplacental perfusion pressure (RUPP), and tested whether inducing a comparable sFlt-1/PlGF imbalance by infusing sFlt-1 (10 μg·kg(-1)·day(-1)) in day 14 pregnant (Preg) rats cause similar increases in blood pressure (BP) and vascular reactivity...
September 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/27270170/soluble-fms-like-tyrosine-kinase-1-promotes-angiotensin-ii-sensitivity-in-preeclampsia
#11
Suzanne D Burke, Zsuzsanna K Zsengellér, Eliyahu V Khankin, Agnes S Lo, Augustine Rajakumar, Jennifer J DuPont, Amy McCurley, Mary E Moss, Dongsheng Zhang, Christopher D Clark, Alice Wang, Ellen W Seely, Peter M Kang, Isaac E Stillman, Iris Z Jaffe, S Ananth Karumanchi
Preeclampsia is a hypertensive disorder of pregnancy in which patients develop profound sensitivity to vasopressors, such as angiotensin II, and is associated with substantial morbidity for the mother and fetus. Enhanced vasoconstrictor sensitivity and elevations in soluble fms-like tyrosine kinase 1 (sFLT1), a circulating antiangiogenic protein, precede clinical signs and symptoms of preeclampsia. Here, we report that overexpression of sFlt1 in pregnant mice induced angiotensin II sensitivity and hypertension by impairing endothelial nitric oxide synthase (eNOS) phosphorylation and promoting oxidative stress in the vasculature...
July 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27133598/replicative-capacity-of-%C3%AE-cells-and-type-1-diabetes
#12
REVIEW
Diane Saunders, Alvin C Powers
Efforts to restore β-cell number or mass in type 1 diabetes (T1D) must combine an intervention to stimulate proliferation of remaining β-cells and an intervention to mitigate or control the β-cell-directed autoimmunity. This review highlights features of the β-cell, including it being part of a pancreatic islet, a mini-organ that is highly vascularized and highly innervated, and efforts to promote β-cell proliferation. In addition, the β-cell in T1D exists in a microenvironment with interactions and input from other islet cell types, extracellular matrix, vascular endothelial cells, neuronal projections, and immune cells, all of which likely influence the β-cell's capacity for replication...
July 2016: Journal of Autoimmunity
https://www.readbyqxmd.com/read/26969425/-tyrosine-kinase-inhibitors-and-pregnancy-a-risk-to-the-fetus
#13
REVIEW
Cécile Jovelet, Sophie Broutin, Sophie Gil, Olivier Mir, Angelo Paci
The association of cancer and pregnancy is increasingly frequent. This is related, partially, to the increasingly belated age of pregnancy. The management of cancer in pregnancy is a complicated issue. The use of tyrosine kinase inhibitors (TKIs) during pregnancy remains rare and only few data are available concerning their transplacental passage. The aim of this work is to review the data described in the literature, in order to highlight the risks incurred by the fetus, associated with these TKIs' treatment...
May 2016: Bulletin du Cancer
https://www.readbyqxmd.com/read/26930265/attenuation-of-hyperglycemia-induced-apoptotic-signaling-and-anti-angiogenic-milieu-in-cultured-cytotrophoblast-cells
#14
Chase Cawyer, Syeda H Afroze, Nathan Drever, Steven Allen, Richard Jones, David C Zawieja, Thomas Kuehl, M Nasir Uddin
OBJECTIVE: Preeclampsia (preE) is a hypertensive disorder that occurs 20% in diabetic pregnancy. We have shown that hyperglycemia impairs cytotrophoblast cell (CTB) function. In this study, we assess apoptotic and anti-angiogenic signaling in excess glucose-induced CTBs. STUDY DESIGN: Human extravillous CTBs (Sw. 71) were treated with 100, 150, 200, 300, or 400 mg/dL glucose for 48 h. Some cells were pretreated with a p38 inhibitor (SB203580) or a peroxisome proliferator-activated receptor gamma (PPARγ) ligand (rosiglitazone) or with D-mannitol...
May 2016: Hypertension in Pregnancy
https://www.readbyqxmd.com/read/26879546/quality-of-life-and-long-term-therapy-in-patients-with-chronic-myeloid-leukemia
#15
REVIEW
Kathryn E Flynn, Ehab Atallah
Since the development of imatinib and other tyrosine kinase inhibitors (TKIs), the prognosis for patients with chronic myeloid leukemia (CML) has markedly improved, such that most patients diagnosed with CML can now expect to live with their disease rather than die from it. However, most patients will require long-term treatment, which has deleterious effects on health-related quality of life. We review recent literature on drug-related adverse effects, long-term medication adherence, limitations to fertility and pregnancy, effects on cognitive function, ability to work, financial toxicity, pediatric populations, and treatment discontinuation...
April 2016: Current Hematologic Malignancy Reports
https://www.readbyqxmd.com/read/26855508/obstetric-complications-and-management-in-chronic-myeloid-leukemia
#16
Minakshi Rohilla, Rakhi Rai, Uday Yanamandra, Neelam Chaudhary, Pankaj Malhotra, Neelam Varma, Vanita Jain, G R V Prasad, Jasvinder Kalra, Subhash C Varma
Chronic myeloid leukaemia (CML) is amongst the most common haematological malignancies encountered in adults. The younger age of onset and increased incidence of CML in Indians leads to higher chances of encountering it in pregnancy. Pregnancy in CML is a complex situation as first line therapy with tyrosine kinase inhibitors (TKI), is fraught with multiple fetal safety issues. The fetal aspects have been elucidated in literature, but there is scarcity of information on the obstetric outcome per se in presence of CML, excluding the influence of TKI...
March 2016: Indian Journal of Hematology & Blood Transfusion
https://www.readbyqxmd.com/read/26721779/metformin-as-a-prevention-and-treatment-for-preeclampsia-effects-on-soluble-fms-like-tyrosine-kinase-1-and-soluble-endoglin-secretion-and-endothelial-dysfunction
#17
Fiona C Brownfoot, Roxanne Hastie, Natalie J Hannan, Ping Cannon, Laura Tuohey, Laura J Parry, Sevvandi Senadheera, Sebastian E Illanes, Tu'uhevaha J Kaitu'u-Lino, Stephen Tong
BACKGROUND: Preeclampsia is associated with placental ischemia/hypoxia and secretion of soluble fms-like tyrosine kinase 1 and soluble endoglin into the maternal circulation. This causes widespread endothelial dysfunction that manifests clinically as hypertension and multisystem organ injury. Recently, small molecule inhibitors of hypoxic inducible factor 1α have been found to reduce soluble fms-like tyrosine kinase 1 and soluble endoglin secretion. However, their safety profile in pregnancy is unknown...
March 2016: American Journal of Obstetrics and Gynecology
https://www.readbyqxmd.com/read/26717314/role-of-endothelin-in-preeclampsia-and-hypertension-following-antiangiogenesis-treatment
#18
REVIEW
Langeza Saleh, Jan A H Danser, Anton H van den Meiracker
PURPOSE OF REVIEW: Preeclampsia is a systemic, pregnancy-related disorder featuring hypertension and proteinuria arising from placental overproduction of soluble FMS-like tyrosine kinase-1, resulting in an antiangiogenic state because of the inhibition of the vascular endothelial growth factor (VEGF) family. Similarly, antiangiogenetic treatment aimed at targeting VEGF in patients with cancer is associated with a preeclampsia-like syndrome. In this study we discuss the pathophysiological role of an activated endothelin system in both conditions...
March 2016: Current Opinion in Nephrology and Hypertension
https://www.readbyqxmd.com/read/26711557/chronic-myeloid-leukemia-in-pregnancy-an-absolute-contraindication-to-neuraxial-anesthesia
#19
J N Owsiak, A S Bullough
Chronic myeloid leukemia is rare in pregnancy with an estimated incidence of 1:75000. It is a genetic myeloproliferative disorder marked by increased and unregulated growth of myeloid cells in the bone marrow. The terminal phase of chronic myeloid leukemia may develop into a blast crisis, defined as >30% myeloblasts in the circulation. A blast crisis resembles an acute leukemia and is associated with rapid clinical deterioration and short survival. Targeted gene therapy with tyrosine kinase inhibitors is effective in treatment but when these agents are discontinued, as in pregnancy, the patient may relapse and blast cells may enter the circulation...
February 2016: International Journal of Obstetric Anesthesia
https://www.readbyqxmd.com/read/26657232/outcome-of-3-pregnancies-in-a-patient-with-chronic-myeloid-leukemia-who-received-3-types-of-tyrosine-kinase-inhibitors-each-in-different-pregnancy-follow-up-of-the-case-with-a-review-of-published-reports
#20
REVIEW
Hussain Alizadeh, Hassan Jaafar, Béla Kajtár
The management of patients with chronic myeloid leukemia (CML) during pregnancy remains a matter of continuous debate. Tyrosine kinase inhibitors (TKIs) have become the standard of care in managing patients with CML. These drugs have a good safety profile, but animal studies have shown that they are potentially teratogenic. Therefore, these drugs are not recommended for use during pregnancy or if a female patient plans to conceive. Despite the extensive clinical experience with TKIs, the available information about the effects of TKIs on fertility, pregnancy, and outcome of babies who were exposed to TKIs during pregnancy and lactation is limited...
November 2015: Annals of Saudi Medicine
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