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Tyrosine kinase inhibitors and pregnancy

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https://www.readbyqxmd.com/read/28721056/onset-of-chronic-myeloid-leukemia-with-complex-karyotype-in-a-pregnant-patient-case-report-and-revision-of-literature
#1
Nicola Sgherza, Elisabetta Abruzzese, Gianni Perla, Maria Marta Minervini, Vincenzo Chiello, Natale Sciannamè, Nicola Cascavilla
Approximately 10%-12% of patients in chronic-phase chronic myeloid leukemia (CP-CML) have additional chromosomal aberrations at diagnosis; moreover, CML occurs in up to 10% of pregnancy-associated leukemias, with an annual incidence of 1 per 100,000 pregnancies. In this report we describe the case of a 36-year-old female with CP-CML diagnosed in the 18th week of pregnancy and with a new complex variant translocation t(4;9;22;21)(q24;q34;q11;q22) and an additional chromosomal aberration t(1;20)(p36;p11). In consideration of her pregnancy, the patient strictly monitored her blood cell count without any specific treatment...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/28716993/low-soluble-fms-like-tyrosine-kinase-1-endoglin-and-endothelin-1-levels-in-women-with-confirmed-or-suspected-preeclampsia-using-proton-pump-inhibitors
#2
Langeza Saleh, Raaho Samantar, Ingrid M Garrelds, Anton H van den Meiracker, Willy Visser, A H Jan Danser
Patients with preeclampsia display elevated placenta-derived sFlt-1 (soluble Fms-like tyrosine kinase-1) and endoglin levels and decreased placental growth factor levels. Proton pump inhibitors (PPIs) decrease trophoblast sFlt-1 and endoglin secretion in vitro. PPIs are used during pregnancy to combat reflux disease. Here, we investigated whether PPIs affect sFlt-1 in women with confirmed/suspected preeclampsia, making use of a prospective cohort study involving 430 women. Of these women, 40 took PPIs (6 esomeprazole, 32 omeprazole, and 2 pantoprazole) for 8 to 45 (median 29) days before sFlt-1 measurement...
July 17, 2017: Hypertension
https://www.readbyqxmd.com/read/28703026/placental-transfer-of-tyrosine-kinase-inhibitors-used-for-chronic-myeloid-leukemia-treatment
#3
Ekaterina Chelysheva, Anna Turkina, Evgenia Polushkina, Roman Shmakov, Alexey Zeifman, Sergey Aleshin, Igor Shokhin, Dorel Guranda, Oksana Oksenjuk, Sergey Mordanov, Khamida Kazakbaeva, Ghermes Chilov
Both favorable pregnancy outcomes and fetal abnormalities have been associated with the use of tyrosine kinase inhibitors (TKIs) during pregnancy. The placental transfer of TKIs in humans is poorly understood. We observed women with chronic myeloid leukemia who used imatinib or nilotinib during the late pregnancy stages. The newborns had no birth abnormalities. We evaluated the drug concentrations in maternal blood, umbilical cord blood, and placental samples collected during labor. We found limited placental transfer of the TKIs...
July 13, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28662830/matrix-metalloproteinases-in-normal-pregnancy-and-preeclampsia
#4
Juanjuan Chen, Raouf A Khalil
Normal pregnancy is associated with marked hemodynamic and uterine changes that allow adequate uteroplacental blood flow and uterine expansion for the growing fetus. These pregnancy-associated changes involve significant uteroplacental and vascular remodeling. Matrix metalloproteinases (MMPs) are important regulators of vascular and uterine remodeling. Increases in MMP-2 and MMP-9 have been implicated in vasodilation, placentation, and uterine expansion during normal pregnancy. The increases in MMPs could be induced by the increased production of estrogen and progesterone during pregnancy...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28607126/mechanisms-and-treatment-of-halogen-inhalation-induced-pulmonary-and-systemic-injuries-in-pregnant-mice
#5
James A Lambert, Matthew A Carlisle, Adam Lam, Saurabh Aggarwal, Stephen Doran, Changchun Ren, Wayne E Bradley, Louis Dell'Italia, Namasivayam Ambalavanan, David A Ford, Rakesh P Patel, Tamas Jilling, Sadis Matalon
Inhalation of oxidant gases has been implicated in adverse outcomes in pregnancy, but animal models to address mechanisms and studies to identify potential pregnancy-specific therapies are lacking. Herein, we show that inhalation of bromine at 600 parts per million for 30 minutes by pregnant mice on the 15th day of embryonic development results in significantly lower survival after 96 hours than an identical level of exposure in nonpregnant mice. On the 19th embryonic day, bromine-exposed pregnant mice have increased systemic blood pressure, abnormal placental development, severe fetal growth restriction, systemic inflammation, increased levels of circulating antiangiogenic short fms-like tyrosine kinase-1, and evidence of pulmonary and cardiac injury...
August 2017: Hypertension
https://www.readbyqxmd.com/read/28383372/maternal-fetal-and-neonatal-imatinib-levels-with-treatment-of-chronic-myeloid-leukemia-in-pregnancy
#6
Richard M Burwick, Kelly Kuo, Diana Brewer, Brian J Druker
BACKGROUND: Pregnant women with chronic myeloid leukemia (CML) can be treated effectively with the tyrosine-kinase inhibitor imatinib, but data regarding fetal and neonatal exposure and safety are limited. CASE: We present a patient with newly diagnosed CML in early pregnancy. Leukapheresis and interferon-α were initiated in the second trimester with limited benefit. Imatinib was subsequently started at 28 weeks of gestation with complete hematologic response within 4 weeks...
May 2017: Obstetrics and Gynecology
https://www.readbyqxmd.com/read/28369651/editor-s-highlight-placentaldisposition-and-effects-of-crizotinib-an-ex-vivo-study-in-the-isolated-dual-side-perfused-human-cotyledon
#7
Gaby A M Eliesen, Petra van den Broek, Jeroen J van den Heuvel, Albert Bilos, Jeanne Pertijs, Joris van Drongelen, Frans G M Russel, Rick Greupink
Tyrosine kinase inhibitors (TKIs) play an important role in cancer pharmacotherapy, yet there is limited data on their use during pregnancy. We studied placental disposition and placental toxicity of crizotinib, a TKI used to treat nonsmall cell lung cancer. Term placentas were perfused for 3 h with crizotinib (1 µM) using the ex vivo dual-side cotyledon perfusion technique. Interference of TKIs with trophoblast viability was studied using BeWo cells. Expression of P-glycoprotein (P-gp) and Breast Cancer Resistance Protein (BCRP) in placental tissue was assessed by immunohistochemistry and inhibition of these transporters was determined in vitro by transport studies with membrane vesicles overexpressing human P-gp or BCRP...
June 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28203373/a-silent-skull-metastatic-follicular-thyroid-carcinoma-mimicking-as-a-benign-scalp-tumor-in-a-pregnant-woman
#8
Tsung-Chun Huang, Yu-Kai Cheng, Tsung-Wei Chen, Yung-Chang Hsu, En-Wei Liu, Hsin-Han Chen
Thyroid cancer with cranial metastasis in a pregnant woman is very rare. In the literature, most cases are diagnosed early from neurogenic signs or symptomatic thyroid gland. Pregnancy also contributes to a hesitation toward early surgical and medical treatments. We reported a scalp tumor in a physically healthy 37-year-old pregnant female with a follicular thyroid carcinoma (FTC) with lung, bone and cranial metastasis in initial presentation. Silent neurogenic and physical examinations make an early diagnosis very challenging...
2017: Endocrinology, Diabetes & Metabolism Case Reports
https://www.readbyqxmd.com/read/28115513/proton-pump-inhibitors-decrease-soluble-fms-like-tyrosine-kinase-1-and-soluble-endoglin-secretion-decrease-hypertension-and-rescue-endothelial-dysfunction
#9
Kenji Onda, Stephen Tong, Sally Beard, Natalie Binder, Masanaga Muto, Sevvandi N Senadheera, Laura Parry, Mark Dilworth, Lewis Renshall, Fiona Brownfoot, Roxanne Hastie, Laura Tuohey, Kirsten Palmer, Toshihiko Hirano, Masahito Ikawa, Tu'uhevaha Kaitu'u-Lino, Natalie J Hannan
Preeclampsia is a severe complication of pregnancy. Antiangiogenic factors soluble fms-like tyrosine kinase-1 (sFlt-1) and soluble endoglin are secreted in excess from the placenta, causing hypertension, endothelial dysfunction, and multiorgan injury. Oxidative stress and vascular inflammation exacerbate the endothelial injury. A drug that can block these pathophysiological steps would be an attractive treatment option. Proton pump inhibitors (PPIs) are safe in pregnancy where they are prescribed for gastric reflux...
March 2017: Hypertension
https://www.readbyqxmd.com/read/27995032/successful-pregnancy-and-delivery-in-a-patient-with-chronic-myeloid-leukemia-a-case-report-and-review-of-the-literature
#10
Weiwei Sheng, Naitong Sun
INTRODUCTION: Complications associated with chronic myeloid leukemia (CML) during pregnancy are rare, and management is challenging because very limited data are available on this patient group. CASE DESCRIPTION: We herein report a successful pregnancy and delivery in a patient diagnosed with CML. The patient was treated with imatinib (400 mg/day) as a first-line therapy. However, she became pregnant while she was in complete hematological remission and had a complete cytogenetic response...
2016: SpringerPlus
https://www.readbyqxmd.com/read/27939478/gelsolin-is-an-endogenous-inhibitor-of-syncytiotrophoblast-extracellular-vesicle-shedding-in-pregnancy
#11
Neil A Nadkarni, Augustine Rajakumar, Nikita Mokhashi, Suzanne D Burke, Sarosh Rana, Saira Salahuddin, Quynh Dang, Ravi Thadhani, Ramaswamy Krishnan, Thomas P Stossel, S Ananth Karumanchi
BACKGROUND: Preeclampsia, a pregnancy-specific inflammatory disorder, is characterized by high levels of anti-angiogenic protein, soluble fms-like tyrosine kinase 1 (sFlt1), in the maternal circulation. sFlt1 producing molecular machinery is present in syncytiotrophoblast extracellular vesicles that are released by the placenta into maternal plasma during normal pregnancy, a process greatly accelerated in preeclampsia. We hypothesized that syncytiotrophoblast extracellular vesicles exposes cytoplasmic actin to plasma resulting in depletion of plasma gelsolin (pGSN), an abundant plasma protein that scavenges circulating actin and other pro-inflammatory mediators...
October 2016: Pregnancy Hypertension
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
#12
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
#13
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...
2016: Anticancer Research
https://www.readbyqxmd.com/read/27856999/simvastatin-alleviates-pathology-in-a-rat-model-of-preeclampsia-involving-erk-mapk-pathway
#14
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
#15
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...
December 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
#16
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
#17
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
#18
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
#19
REVIEW
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
#20
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
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