Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018681 (headache)
 56,091 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tyrosine kinase receptors play an important role in tumor angiogenesis and, their implication in epithelial thyroid tumor growth has been highlighted. Sunitinib is a novel tyrosine kinase inhibitor, approved in 2006 by Food and Drug Administration for the treatment of advanced renal cell and gastrointestinal stromal tumors. Preliminary promising results have been also obtained in patients with RAI-resistant thyroid neoplasia. In the current study, our experience on 9 patients with advanced thyroid epithelial cancer is analyzed and discussed in relation to the new patents in this field. According to RECIST criteria, partial response was obtained in 5/9 (55.5%) patients at 3 months and in 6/9 (66.6%) at 6 months. Median treatment follow-up was 13.0 months and median overall survival and progression-free survival were 20 [95% confidence interval (CI) 9.3 - 30.6] and 21 months (95% CI 6.9 - 35.1), respectively. One case of severe thoracic hemorrhage was observed, the most common adverse events being represented by fatigue, (44.4% ), skin rash (33.3% ), headache (33.3% ), and one case each of hypertension, macrocytosis and acute pneumonia. These results confirm sunitinib as a potential useful tool for the treatment of advanced thyroid cancers and may open the way for new patents of molecules with more specific target selectivity.
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PMID:Off-label use of sunitinib in patients with advanced, epithelial thyroid cancer: a retrospective analysis. 2253 21

Receptor tyrosine kinases (RTKs) bearing oncogenic mutations in EGFR, ALK and ROS1 occur in a significant subset of lung adenocarcinomas. Tyrosine kinase inhibitors (TKIs) targeting tumor cells dependent on these oncogenic RTKs yield tumor shrinkage, but also a variety of adverse events. Skin toxicities, hematological deficiencies, nausea, vomiting, diarrhea, and headache are among the most common, with more acute and often fatal side effects such as liver failure and interstitial lung disease (ILD) occurring less frequently. In normal epithelia, RTKs regulate tissue homeostasis. For example, EGFR maintains keratinocyte homeostasis while MET regulates processes associated with tissue remodeling. Previous studies suggest that the acneiform rash occurring in response to EGFR inhibition is a part of an inflammatory response driven by pronounced cytokine and chemokine release and recruitment of distinct immune cell populations. Mechanistically, blockade of EGFR causes a Type I interferon (IFN) response within keratinocytes and in carcinoma cells driven by this RTK. This innate immune response within the tumor microenvironment (TME) involves increased antigen presentation and effector T cell recruitment that may participate in therapy response. This TKI-mediated release of inflammatory suppression represents a novel tumor cell vulnerability that may be exploited by combining TKIs with immune-oncology (IO) agents that rely on T-cell inflammation for efficacy. However, early clinical data indicate that combination therapies enhance the frequency and magnitude of the more acute adverse events, especially pneumonitis, hepatitis, and pulmonary fibrosis. Further preclinical studies to understand TKI mediated inflammation and crosstalk between normal epithelial cells, cancer cells, and the TME are necessary to improve treatment regimens for patients with RTK-driven carcinomas.
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PMID:Linking tyrosine kinase inhibitor-mediated inflammation with normal epithelial cell homeostasis and tumor therapeutic responses. 3065 89

Intracerebral hemorrhage (ICH) is an unusual complication in chronic myeloid leukemia (CML). Intracranial involvement, causing ICH as an initial presentation is extremely rare in CML. Herein, we reported the first case of a newly diagnosed CML patient, who presented with headaches accompanied by nausea and vomiting as the initial presentations, caused by ICH. He underwent an emergency craniotomy twice and the postoperative pathologic examination confirmed intracranial CML involvement. Interestingly, his bone marrow and cerebrospinal fluid (CSF) smear and pathological study of the involved brain tissue showed proliferation of granulocytes, which were comprised mainly of metamyelocytes and myelocytes, without any blast within the brain tissue, suggesting the stage of CML was in the chronic phase (CP). He then received dasatinib treatment and achieved complete hematologic remission in the first 3-month follow-up but failed to reach a molecular response in the 6-month follow-up. By reporting this case and reviewing relevant references, we suggested intracranial CML involvement should be considered as a potential pathogenesis of ICH when the patient presents with hyperleukocytosis. A craniotomy is mainly for intracranial decompression and benefits the diagnosis of intracranial CML involvement. Tyrosine kinase inhibitors are effective in such patients to some extent, but more appropriate treatment strategies should be investigated in further detail.
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PMID:Intracerebral Hemorrhage as the Initial Presentation of Chronic Myeloid Leukemia: A Case Report and Review of the Literature. 3319 17