Pilot study of huachansu in patients with hepatocellular carcinoma, nonsmall‐cell lung cancer, or pancreatic cancer

Abstract

Objective To investigate the molecular mechanisms of CCL13/monocyte chemoattractant protein 4 (MCP‐4) chemokine expression through proinflammatory cytokines in different primary human fibroblasts and the contribution of CCL13 to monocyte migration. Methods Using RNase protection assays and enzyme‐linked immunosorbent assays, we quantified the expression of CCL13 compared with that of CCL2/MCP‐1 in primary human fibroblasts. Boyden chamber assays were performed to determine the importance of CCL13 for migration of primary monocytes. Pharmacologic inhibitors as well as small interfering RNA knockdown approaches were used to investigate the signaling pathways regulating CCL13 expression. Results The interleukin‐6 (IL‐6)–type cytokine oncostatin M (OSM) was a powerful inducer of CCL13 expression in primary synovial fibroblasts from patients with rheumatoid arthritis (RA) as well as those from healthy control subjects but not in other types of fibroblasts. Neither IL‐6 nor tumor necrosis factor α could stimulate the expression of CCL13 in synovial fibroblasts; IL‐1β was a very weak inducer. Synovial fibroblasts from patients with RA constitutively produced low amounts of CCL13, which was partially dependent on constitutive production of OSM. By investigating the underlying molecular mechanism, we identified STAT‐5, ERK‐1/2, and p38 as critical factors involved in OSM‐dependent transcription and messenger RNA stabilization of CCL13. Conclusion In contrast to other prominent cytokines involved in the pathogenesis of RA, OSM can strongly up‐regulate the expression of CCL13, a chemokine recently identified in the synovial fluid of patients with RA. Despite potent OSM‐induced signal transduction in all types of fibroblasts analyzed, only synovial fibroblasts secreted CCL13, which might be indicative of tissue‐specific imprinting of different fibroblasts during development.

Bufalin, a Traditional Oriental Medicine, Induces Apoptosis in Human Cancer Cells

“…One of these patients (with hepatocellular cancer) had 20% regression (duration, 11 months). Plasma bufalin concentration reached maximal levels at the end of the 2-hour infusion and was proportional to the amount of drug being administered (0.81-3.38 ng/mL) (Meng et al, 2009). …”

Effects of bufalin on the proliferation of human lung cancer cells and its molecular mechanisms of action

“…Therefore, it is necessary to develop new anticancer agents that could produce the most effective targeted cancer therapies by their concomitant inhibition of multiple targets. Bufalin is a naturally occurring small-molecule compound from Traditional Chinese Medicine (TCM) Chansu which has been used to treat lung, hepatocellular carcinoma, or pancreatic cancer in human patients (Meng et al 2009). Chansu is the dried venom of toad (Bufo bufo gargarizans CANTOR or Bufo melanostictus SCHNEIDER) and has been used as an Oriental drug (Yasuharu et al 2004).…”

Chromatographic Fingerprint-Bioactivity Relationships of the Antitumor Properties of Bufo bufo gargarizans Skin Extracts

“…Moreover, cinobufacini, an aqueous extract of toad skin, which has been proved to has significant antitumor activity against liver, lung, colon, pancreatic, gastric, esophageal carcinomas [11][12][13][14][15] from in vitro and in vivo datasets, was approved by China Food and Drug Administration (CFDA) for use in clinical treatment.…”