ABSTRACT
We report the case of a 38-year-old female with gastrointestinal amyloidosis who presented with acute abdominal pain. The computed tomography scan showed that the patient had generalized lymphadenopathy. This clinical picture with absolute leukocytosis was interpreted as an acute secondary bacterial process of unspecified etiology with generalized lymphadenopathy. The patient was administered a broad-spectrum antibacterial drug and detoxication therapy. The upper endoscopy revealed bleeding of unknown origin. After a 2-day conservative hemostatic therapy, gastric tumor involvement was suggested during control endoscopy. The human immunodeficiency virus (HIV) antibodies were found with the following confirmation of their specificity by immunoblotting. Histopathological study of the biopsy specimens made it possible to diagnose gastrointestinal AA/AL-amyloidosis complicated by gastrointestinal bleeding.
Subject(s)
Amyloidosis , Gastrointestinal Diseases , HIV Infections , Female , Humans , Adult , Stomach , Amyloidosis/complications , Amyloidosis/diagnosis , Duodenum/pathology , Gastrointestinal Diseases/diagnosis , HIV Infections/complications , HIV Infections/drug therapyABSTRACT
The renaissance of research into natural products has unequivocally and paradigmatically shifted our knowledge about the significant role of natural products in cancer chemoprevention. Bufalin is a pharmacologically active molecule isolated from the skin of the toad Bufo gargarizans or Bufo melanostictus. Bufalin has characteristically unique properties to regulate multiple molecular targets and can be used to harness multi-targeted therapeutic regimes against different cancers. There is burgeoning evidence related to functional roles of signaling cascades in carcinogenesis and metastasis. Bufalin has been reported to regulate pleiotropically a myriad of signal transduction cascades in various cancers. Importantly, bufalin mechanistically regulated JAK/STAT, Wnt/ß-Catenin, mTOR, TRAIL/TRAIL-R, EGFR, and c-MET pathways. Furthermore, bufalin-mediated modulation of non-coding RNAs in different cancers has also started to gain tremendous momentum. Similarly, bufalin-mediated targeting of tumor microenvironments and tumor macrophages is an area of exciting research and we have only started to scratch the surface of the complicated nature of molecular oncology. Cell culture studies and animal models provide proof-of-concept for the impetus role of bufalin in the inhibition of carcinogenesis and metastasis. Bufalin-related clinical studies are insufficient and interdisciplinary researchers require detailed analysis of the existing knowledge gaps.
Subject(s)
Bufanolides , beta Catenin , Animals , beta Catenin/metabolism , Cell Line, Tumor , Signal Transduction , TOR Serine-Threonine Kinases/metabolism , Bufanolides/pharmacology , Carcinogenesis , Apoptosis , Tumor MicroenvironmentABSTRACT
Landmark discoveries in molecular oncology have provided a wide-angle overview of the heterogenous and therapeutically challenging nature of cancer. The power of modern 'omics' technologies has enabled researchers to deeply and comprehensively characterize molecular mechanisms underlying cellular functions. Interestingly, high-throughput technologies have opened new horizons for the design and scientific fool-proof evaluation of the pharmacological properties of targeted chemical compounds to tactfully control the activities of the oncogenic protein networks. Groundbreaking discoveries have galvanized the expansion of the repertoire of available pharmacopoeia to therapeutically target a myriad of deregulated oncogenic pathways. Natural product research has undergone substantial broadening, and many of the drugs which constitute the backbone of modern pharmaceuticals have been derived from the natural cornucopia. Baicalein has gradually gained attention because of its unique ability to target different oncogenic signal transduction cascades in various cancers. We have partitioned this review into different sub-sections to provide a broader snapshot of the oncogenic pathways regulated by baicalein. In this review, we summarize baicalein-mediated targeting of WNT/ß-catenin, AKT/mTOR, JAK/STAT, MAPK, and NOTCH pathways. We also critically analyze how baicalein regulates non-coding RNAs (microRNAs and long non-coding RNAs) in different cancers. Finally, we conceptually interpret baicalein-mediated inhibition of primary and secondary growths in xenografted mice.
