Lethal and Sub-Lethal Effects and Modulation of Gene Expression Induced by T Kinase Inhibitors in Zebrafish (Danio Rerio) Embryos

Tyrosine kinase inhibitors (TKIs) are designed for targeted cancer therapy. The consumption of these drugs during the last 20 years has been constantly rising. In the zebrafish (Danio rerio) embryo toxicity test, we assessed the toxicity of six TKIs: imatinib mesylate, erlotinib, nilotinib, dasatinib, sorafenib and regorafenib. Imatinib mesylate and dasatinib induced lethal effects, while regorafenib, sorfenib and dasatinib caused a significant increase of sub-lethal effects, predominantly oedema, no blood circulation and formation of blood aggregates. The analyses of the changes in the expression of selected genes associated with the hormone system after the exposure to imatinib mesylate, dasatinib and regorafenib demonstrated that all three tested TKIs deregulated the expression of oestrogen receptor esr1, cytochrome P450 aromatase (cypa19b) and hydroxysteroid-dehydrogenase (hsd3b), regorafenib, and also thyroglobulin (tg). The expression of genes involved in the DNA damage response (gadd45 and mcm6) and apoptosis (bcl2) was deregulated only by exposure to regorafenib. The data indicate that common mechanisms, namely antiangiogenic activity and interference with steroidogenesis are involved in the TKI induced sub-lethal effects and potential hormone disrupting activity, respectively. The residues of TKIs may represent an environmental hazard; therefore, further ecotoxicological studies focusing also on the effects of their mixtures are warranted.

Potential effect of Imatinib on some sex hormones for male patients of Chronic Myelogenous Leukemia in Baghdad province

Imatinib Mesylate is an oral chemotherapy drug that has been used to treat Chronic Myelogenous Leukemia (CML). It works as an inhibitor of oncogene tyrosine kinase BCR-ABLI as a target therapeutic agent. Despite the drug is well tolerated in most patients, impaired testosterone production and Gynecomastia after therapy might happen. The current study aims to evaluate the impact of Imatinib Mesylate on sex hormones of CML male patients in Baghdad province. Blood specimens were collected from (42) CML patients aged 23 to 68 years who used Imatinib drug for more than two years, and (45) normal persons aged 25 to 65 years as a control group. Exclusion criteria were performed for both control and CML patient's groups, including people with diabetes, hypertensive, and males complaining of infertility after taking medical history for every participant. The blood level of hemoglobin (Hb), white blood cells (WBC), platelet count, testosterone, LH, and FSH were evaluated and investigated. The obtained results showed a significantly lower level of testosterone (2.73+- 0.97) ng/mL than the control group (4.72 ±1.02) ng/mL with a p-value of 0.000. While LH (4.53±2.1) mIU/mL and FSH (5.12 ± 2.83) mIU/mL were significantly higher than the control group (3.77± 0.8) mIU/mL and (3.85±0.807) mIU/mL with p-value of 0.026 and 0.005 respectively. Moreover, the outcomes revealed a moderate positive correlation (r = +0.348) between LH hormone levels with a duration increasing time of using Imatinib, while platelet showed a moderate negative correlation (r = -0.321) with time-consuming using that drug. In conclusion, Imatinib might harm testis functions and some hematological parameters that could increase using this drug.

A gastrointestinal Stromal Tumor of the Small Bowel Presenting as an Acute Peritonitis: A Case Report

Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract, GISTs of the small bowel presenting as an acute peritonitis are rare, which necessitates emergency surgery. Presentation of Case: A 44-year-old women presented with severe abdominal pain and nausea. Physical examination revealed a tenderness and muscular defense around the lower abdomen. Laboratory data showed an elevated white blood cell count and C-reactive protein level. An enhanced computed tomography (CT) scan showed a 8 × 10 cm cystic mass in the lower abdomen, which contained air. Emergency laparotomy showed a giant perforated tumor that arose from the ileum, the tumor and affected segment of ileum were resected. the tumor was diagnosed as GIST in low-risk category, and imatinib mesylate was initiated, The patiente had an uneventful postoperative course and remains well. Discussion and Conclusion: Such rare cases can be diagnosed and treated properly with careful clinical evaluation, Computed tomography (CT) is the gold standard for imaging that is used to characterize any abdominal mass. Surgical resection is still the first-line treatment for patients with primary localized and resectable small bowel GIST and adjuvant chemotherapy with imatinib mesylate is indicated in patients with high-risk small bowel GIST.