Activation of human HSC is suppressed by human platelets or platelet-derived ATP via adenosine-cAMP signaling pathway in vitro. Therefore, platelets have the possibility to be used in the treatment of liver cirrhosis.

No abstract

(-)-Epigallocatechin-3-gallate (EGCG), the major constituent of green tea, has been shown to inhibit cell proliferation and induce apoptosis in several types of human tumors. The most common site of distant metastases in colorectal cancer is the liver. However, no previous studies have reported the ability of EGCG to suppress liver metastases of human colorectal cancer. The aim of the present study was to elucidate the potential use of EGCG as chemotherapy targeting liver metastases of human colorectal cancer. To assess the effect of EGCG on human colorectal cancer cell lines, RKO and HCT116, cell viability, cell proliferation and apoptosis were measured by cell counting kit-8, BrdU assay and TUNEL staining, respectively. Protein and gene expression were measured by western blot analysis and RT-PCR analysis, respectively. EGCG inhibited cell proliferation and induced apoptosis. EGCG dephosphorylated constitutively activated Akt and increased the activation of p38. EGCG also decreased the expression of vascular endothelial growth factor receptor 2. Additionally, the ability of EGCG to prevent the development of liver metastases of RKO tumors was evaluated in SCID mice. EGCG suppressed angiogenesis and induced apoptosis in liver metastases without associated body weight loss or hepatotoxicity. Furthermore, the liver metastatic area was significantly reduced by EGCG administration. Our findings indicate that EGCG may be useful in the treatment of liver metastases of human colorectal cancer.

No abstract

Aim Sphingosine 1‐phosphate (S1P) is a bioactive sphingolipid metabolite released from erythrocytes and platelets, and is a potent stimulus for endothelial cell proliferation. However, the role of S1P on human liver sinusoidal endothelial cells (LSEC) remains unclear. The proliferation and inhibition of apoptosis in LSEC are involved in the promotion of liver regeneration and the suppression of liver injury after liver resection and transplantation. The aim of this study is to investigate the role of S1P on human LSEC and the interaction between S1P and LSEC in hepatocyte proliferation in vitro. Methods Immortalized human LSEC were used. LSEC were cultured with S1P, and the cell proliferation, anti‐apoptosis, signal transductions and production of cytokines and growth factors were subsequently examined. To investigate the interaction between S1P and LSEC in hepatocyte proliferation, primary human hepatocytes were cultured with the supernatants of LSEC with and without S1P. DNA synthesis and signal transductions in hepatocytes were examined. Results S1P induced LSEC proliferation through activation of Akt and extracellular signal‐related kinase pathways and suppressed LSEC apoptosis by affecting the expression levels of Bcl‐2, Bax and cleaved caspase‐3. S1P promoted interleukin‐6 (IL‐6) and vascular endothelial growth factor (VEGF) production in LSEC. The supernatants of LSEC cultured with S1P enhanced hepatocyte DNA synthesis more strongly than the supernatants of LSEC cultured without S1P through activation of the signal transducer and activator of transcription‐3 pathway. Conclusion S1P has proliferative and anti‐apoptotic effects and promotes the production of IL‐6 and VEGF in human LSEC, thereby promoting hepatocyte proliferation.

TPO had no proliferative effect on HCC in vitro or in vivo, and could therefore be useful in the treatment of liver cirrhosis.

Platelets contain three types of granules: alpha granules, dense granules, and lysosomal granules. Each granule contains various growth factors, cytokines, and other physiological substances. Platelets trigger many kinds of biological responses, such as hemostasis, wound healing, and tissue regeneration. This review presents experimental evidence of platelets in accelerating liver regeneration and improving liver fibrosis. The regenerative effect of liver by platelets consists of three mechanisms; i.e., the direct effect on hepatocytes, the cooperative effect with liver sinusoidal endothelial cells, and the collaborative effect with Kupffer cells. Many signal transduction pathways are involved in hepatocyte proliferation. One is activation of Akt and extracellular signal-regulated kinase (ERK)1/2, which are derived from direct stimulation from growth factors in platelets. The other is signal transducer and activator of transcription-3 (STAT3) activation by interleukin (IL)-6 derived from liver sinusoidal endothelial cells and Kupffer cells, which are stimulated by contact with platelets during liver regeneration. Platelets also improve liver fibrosis in rodent models by inactivating hepatic stellate cells to decrease collagen production. The level of intracellular cyclic adenosine monophosphate (cyclic AMP) is increased by adenosine through its receptors on hepatic stellate cells, resulting in inactivation of these cells. Adenosine is produced by the degradation of adenine nucleotides such as adenosine diphosphate (ADP) and adenosine tri-phosphate (ATP), which are stored in abundance within the dense granules of platelets.

While there have been numerous reports about colovesical fistulas and ruptured intestinal diverticula, there have been far fewer reports about vesicointestinal fistulas caused by Meckel's diverticula. Most Meckel's diverticula are asymptomatic. Furthermore, they seldom cause vesicointestinal fistulas, and the associated complications are non-specific. Thus, their preoperative diagnosis is difficult. We experienced a case in which a vesicointestinal fistula was caused by a Meckel's diverticulum and was treated with laparoscopic surgery. A 46-year-old male was referred to our hospital after exhibiting hematuria. Cystoscopy revealed a fistula between the small intestine and bladder. Contrast-enhanced computed tomography and magnetic resonance imaging showed a diverticulum in the ileum and a fistula between the ileum and bladder, which passed through the diverticulum. A Meckel's diverticulum was suspected. We conducted a laparoscopic operation. We dissected the Meckel's diverticulum with an automatic suturing device and removed it together with part of the ileum. The patient's postoperative course was good. We experienced a case in which a vesicointestinal fistula was caused by a Meckel's diverticulum and was successfully treated with laparoscopic surgery. In selected cases of Meckel's diverticulum, the dissection of the diverticulum with an automatic suturing device is appropriate.