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In silico approaches for the identification of novel FGFR1 inhibitor in cancer: A fragment-based De novo drug designing guided virtual screening approach.

The fibroblast growth factor receptor 1 (FGFR1) plays a crucial role in cancer development and progression, primarily through mechanisms involving carcinogenesis and angiogenesis. Aberrant FGFR1 signalling has been implicated in various cancers, including lung, breast, neck and urothelial carcinoma. Despite the recognized oncogenic potential of FGFR1, therapeutic strategies targeting its kinase domain remain inadequately explored. This underscores an urgent need for the development of novel FGFR1 inhibitors, particularly through de novo drug design approaches, to effectively counteract FGFR1-d

Ginkgo biloba L. extract prevents steroid-induced necrosis of the femoral head by rescuing apoptosis and dysfunction in vascular endothelial cells via the PI3K/AKT/eNOS pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Ginkgo biloba L. extract (EGb) is one of the world's most extensively used herbal medicines. Due to the diverse pharmacological properties of EGb, it has been used in the treatment of neurological illnesses, as well as cardiovascular and cerebrovascular ailments. However, the effect and pharmacological mechanism of EGb on steroid-induced necrosis of the femoral head (SINFH) are still unclear. AIM OF THE STUDY: SINFH remains a challenging problem in orthopedics. Previous investigations have shown that EGb has the potential to reduce the occurrence of SINFH. The

Discovery of VEGFR-2 Inhibitors From Leonurus japonicus via Integrated Genetic Authentication, Molecular Networking, and In Silico Analysis.

Angiogenesis, regulated by vascular endothelial growth factor (VEGF), is crucial in tumor growth, metastasis, and inflammation. Leonurus japonicus Houtt., a traditional Chinese herb, was investigated for its anti-angiogenic potential. DNA sequencing confirmed its identity, distinguishing it from the common morphological misidentification with Leonurus sibiricus by the public. Using UHPLC-MS/MS and GNPS (Global Natural Products Social) molecular networking on the active methanol partition, over 6000 nodes were grouped into 273 clusters. Diterpenoids and flavonoids were targeted. Six compounds w

Therapeutic Management of Metastatic Thymoma and Thymic Carcinoma.

PURPOSE OF THE REVIEW: Assess new options and best sequence or combination strategies for the treatment of metastatic thymic epithelial tumors. RECENT FINDINGS: Besides historical cytotoxic chemotherapy regimens, which remain standard-of-care for many patients with thymoma, new options include antiangiogenic agents and immune checkpoint inhibitors (ICIs) in the first-line setting combined with carboplatin and paclitaxel for thymic carcinoma. Antiangiogenic agents are also used in the second-line setting, possibly sequenced or combined with ICIs. With the latter, comprehensive assessment for a

Mass balance, metabolic disposition, and pharmacokinetics of a novel selective inhibitor of PI3Kδ [14C] SHC014748M in healthy Chinese subjects following oral administration.

PURPOSE: SHC014748M is a potent, novel selective PI3Kδ isoform inhibitor and is proposed for the treatment of non-Hodgkin lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma. This study investigated the pharmacokinetics, mass balance, metabolism and excretion of SHC014748M in Chinese male subjects following a single oral dose of 150 mg (100 μCi) [14C] SHC014748M. METHODS: Six healthy Chinese male subjects administrated an oral suspension of 150 mg (100 μCi) [14C] SHC014748M and the samples of blood, urine and feces were collected for measuring. Liquid chromatography-tandem ma

New developments in the medical treatment of endometriosis.

Endometriosis affects 1 in 10 women of reproductive-age. The current treatments are surgical and hormonal but have limitations, including the risk of recurrence, side effects, contraceptive action for women who desire pregnancy, and cost. New treatments include gonadotropin-releasing hormone analogues, selective progesterone (or estrogen) receptor modulators, aromatase inhibitors, immunomodulators, and antiangiogenic agents. Further research is needed into central sensitization, local neurogenesis, and the genetics of endometriosis to identify additional treatment targets. A wider range of med

Corneal neovascularization and biological therapy.

Corneal avascularity is necessary for the preservation of optimal vision. The cornea maintains a dynamic balance between pro- and antiangiogenic factors that allows it to remain avascular under normal homeostatic conditions. Corneal neovascularization (NV) is a condition that can develop in response to inflammation, hypoxia, trauma, or limbal stem cell deficiency and it is a significant cause of blindness. New therapeutic options for diseases of the cornea and ocular surface are now being explored in experimental animals and clinical trials. Antibody based biologics are being tested for their

VEGF inhibition, hypertension, and renal toxicity.

The use of anti-angiogenic agents as part of the therapeutic armamentarium for advanced stage solid tumors has become the standard of care in several instances, particularly for renal cell carcinoma, non-small cell lung carcinoma, colorectal carcinoma, and gastrointestinal stromal tumors. These agents primarily target vascular endothelial growth factor (VEGF) and/or its receptors, and include bevacizumab, a humanized monoclonal antibody against VEGF, as well as tyrosine kinase inhibitors that target several receptor tyrosine kinases (RTK), including VEGF receptors. These therapies, as a genera

Treatment of Kaposi's sarcoma--an update.

Kaposi's sarcoma (KS) is an angioproliferative disease of multifactorial origin arising in different clinic-epidemiologic forms, which show the same histopathological features. It generally starts as a hyperplastic reactive-inflammatory and angiogenic process, which may evolve into monomorphic nodules of KS cells that can be clonal (late-stage lesions) and resemble a true sarcoma. Infection with the human herpesvirus 8, cytokine- and angiogenic factor-induced growth together with an immuno-dysregulated state represent fundamental conditions for the development of this tumor. Several local ther

Exploration of the mechanism of anlotinib in reversing PD-1 immunotherapy resistance: insights from single-cell sequencing.

Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis have revolutionized cancer therapy, yet primary and acquired resistance remain major clinical obstacles. Dysregulated angiogenesis fuels the development of an immunosuppressive tumor microenvironment, while crosstalk between immunity and angiogenesis further propels tumor immune evasion and treatment resistance. The present study aimed to establish a penpulimab-resistant model, delineate anti-PD-1 resistance traits via single-cell RNA sequencing, and unravel the precise mechanisms through which anlotinib-an anti-angiogenic agent

[Administering Ramucirumab Safely after Inserting an Intestinal Stent, Due to Peritoneal Metastasis of Gastric Cancer-A Case Report].

The recent phase Ⅲ trials REGARD and RAINBOW have shown survival benefits and acceptable safetyprofiles of ramucirumab( RAM)alone and RAM pl … bition of vascular endothelial growth factors could be the cause of perforation. Thus, the usage of angiogenesis inhibitors such as RAM while intestinal stents are placed, mayincrease the risk of gastrointestinal perforation. We report a case in which RAM was administrated with no adverse events after multiple gastrointestinal metal stents being inserted.

Escaping Antiangiogenic Therapy: Strategies Employed by Cancer Cells.

Tumor angiogenesis is widely recognized as one of the "hallmarks of cancer". Consequently, during the last decades the development and testing of commercial angiogenic inhibitors has been a central focus for both basic and clinical cancer research. While antiangiogenic drugs are now incorporated into standard clinical practice, as with all cancer therapies, tumors can eventually become resistant by employing a variety of strategies to receive nutrients and oxygen in the event of therapeutic assault. Herein, we concentrate and review in detail three of the principal mechanisms of antiangiogenic

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… Currently, there are >800 active clinical trials evaluating angiogenesis inhibitors ( https://clinicaltrials.gov/ ). … However, this process has proven resilient in in vitro treatments with a range of angiogenesis inhibitors, including bevacizumab (Avastin, see Table 1 ) [ 100 , 101 ]. …

Inhibition of MMP synthesis by doxycycline and chemically modified tetracyclines (CMTs) in human endothelial cells.

Doxycycline is a commonly used broad-spectrum antibiotic. Recently, it has been shown that it also inhibits the activity of mammalian collagenases and gelatinases, an activity unrelated to its antimicrobial efficacy. In this study, we show that doxycycline not only inhibits MMP-8 and MMP-9 (gelatinase B) activity, but also the synthesis of MMPs in human endothelial cells. Doxycycline (50 microM) completely inhibited the phorbol-12-myristate-13-acetate (PMA)-mediated induction of MMP-8 and MMP-9, as measured by Western blotting and gelatin zymography, respectively. The inhibition was also obser

Visfatin as a modulator of factors involved in human placental invasion and angiogenesis: interactions with folic acid and aspirin.

CONTEXT: Our previous studies demonstrated the expression of visfatin in the human placenta and its impact on placental cell proliferation and apoptosis. AIMS: This study aimed to examine the effect of visfatin, folic acid (FA), and aspirin (ASA) on markers of invasion and angiogenesis in the human placenta. METHODS: JEG-3 cells and placental villi from normal pregnancies at term were treated for 48 h with visfatin (1 ng/mL, 10 ng/mL or 100 ng/mL) to assess the levels of metalloproteinases (MMP-2/MMP-9), their inhibitors (TIMP-1/TIMP-2), and vascular endothelial growth factors (VEGFA/PLGF).

Acid sphingomyelinase inhibition induces cerebral angiogenesis post-ischemia/reperfusion in an oxidative stress-dependent way and promotes endothelial survival by regulating mitochondrial metabolism.

Acid sphingomyelinase (ASM) inhibitors are widely used for the treatment of post-stroke depression. They promote neurological recovery in animal stroke models via neurorestorative effects. In a previous study, we found that antidepressants including amitriptyline, fluoxetine, and desipramine increase cerebral angiogenesis post-ischemia/reperfusion (I/R) in an ASM-dependent way. To elucidate the underlying mechanisms, we investigated the effects of the functional ASM inhibitor amitriptyline in two models of I/R injury, that is, in human cerebral microvascular endothelial hCMEC/D3 cells exposed

Mechanical strain stimulates vasculogenesis and expression of angiogenesis guidance molecules of embryonic stem cells through elevation of intracellular calcium, reactive oxygen species and nitric oxide generation.

OBJECTIVES: Differentiation of embryonic stem (ES) cells may be regulated by mechanical strain. Herein, signaling molecules underlying mechanical stimulation of vasculogenesis and expression of angiogenesis guidance cues were investigated in ES cell-derived embryoid bodies. METHODS AND RESULTS: Treatment of embryoid bodies with 10% static mechanical strain using a Flexercell strain system significantly increased CD31-positive vascular structures and the angiogenesis guidance molecules plexinB1, ephrin B2, neuropilin1 (NRP1), semaphorin 4D (sem4D) and robo4 as well as vascular endothelial grow

[Assessment of pro- and antiangiogenic factors blood serum concentrations in patients with hormonal inactive adrenal tumors].

INTRODUCTION: The growth and persistence of solid tumors and their metastases is connected with angiogenesis. This process is determined by activity of pro- and antyangiogenic factors. VEGF is the one of the most important factors having a stimulant effect on angiogenesis. Soluble forms of VEGF receptors are inhibitors of angiogenesis. The soluble forms of VEGF receptors containing extra cellular part of receptor, which binds ligand, seem to be real inhibitors of VEGF. THE AIM OF THE STUDY: Evaluation the value of serum VEGF and soluble forms of VEGF receptors concentration as a marker of mal

Global landscape for pulmonary fibrosis treatment: a data-driven perspective from clinical trials.

OBJECTIVE: To systematically map the global landscape, evolution and key characteristics of interventional clinical trials in pulmonary fibrosis, providing an empirical basis for future trial strategies and resource allocation. METHODS: The INFORMA Pharma Intelligence database was searched to identify 1,203 interventional PF trials. Descriptive statistics were applied to analyse temporal trends, geographic distribution, sponsors, trial phase and status, primary endpoints, drug targets or mechanisms, and the disease spectrum. RESULTS: Global pulmonary fibrosis trial activity displayed a three

Novel Strategies for the Management of Hepatocellular Carcinoma with Portal Vein Tumor Thrombus: A Review.

Portal vein tumor thrombus (PVTT) occurs in more than half of patients with hepatocellular carcinoma (HCC) and is associated with markedly shortened survival and a poor prognosis. Historically, management relied mainly on locoregional therapies or upfront surgical resection, but outcomes remained unsatisfactory. In recent years, immune checkpoint inhibitors (ICIs) combined with antiangiogenic targeted therapy have substantially changed the systemic treatment landscape for advanced HCC and created new opportunities for patients with unresectable or borderline-resectable HCC with PVTT to undergo

Safety and efficacy of anlotinib hydrochloride capsules in advanced non-small-cell lung cancer: a multicenter, real-world study.

Objective: To investigate the safety and efficacy of anlotinib hydrochloride capsules in stage III-IV non-small-cell lung cancer (NSCLC). Methods: NSCLC patients received anlotinib monotherapy or combination therapy. The primary end point was adverse reactions during anlotinib treatment and the secondary end point was progression-free survival. Results: During anlotinib treatement, 41.85% (167/399) of patients experienced adverse reactions, and the monotherapy group had a lower incidence than the combination group (36.89 vs 49.68%; p = 0.012). The median progression-free survival of patients i