Akinobu Furutani

PSK induces apoptosis through the inhibition of activated STAT3 in human esophageal carcinoma cells.

PSK, a protein-bound polysaccharide, is widely used in Japan as an immunopotentiating biological response modifier for cancer patients. PSK exerts antitumor activities through stimulation of the hosts immune response; however, few studies have addressed the direct actions of PSK on tumor cells. Recently, it has been found that STAT3 is aberrantly activated in various types of malignancies, and plays a crucial role in tumor cell proliferation and survival. In the present study, STAT3 was constitutively activated in KYSE170 and TE13 esophageal carcinoma cells, and PSK inhibited proliferation and induced apoptosis in these cells in a dose-dependent manner. Based on these findings, the relationship between STAT3 and apoptosis in these cells was investigated. Results showed that PSK inhibited the expression of activated STAT3 and stimulated the expression of pro-apoptotic Bax in a dose-dependent manner, without affecting the expression of anti-apoptotic Bcl-xL and Mcl-1. These results indicate that PSK may induce apoptosis in esophageal carcinoma cells by inhibiting the expression of activated STAT3.

The novel HDAC inhibitor OBP-801/YM753 enhances the effects of 5-fluorouracil with radiation on esophageal squamous carcinoma cells.

Histone deacetylase (HDAC) inhibitors have been shown to enhance the effects of 5-fluorouracil (5-FU) against various cancer cells; however, no report has shown that an HDAC inhibitor may enhance the effects of 5-FU with radiation. Therefore, we investigated whether the novel HDAC inhibitor OBP-801/YM753 could enhance the effects of 5-FU with radiation on esophageal squamous carcinoma KYSE170 cells. The inhibition of the cell growth was significantly stronger with the combination of OBP-801/YM753 with 5-FU than with the 5-FU treatment only. Furthermore, inhibition of the colony formation was the most effective with the combined treatment of OBP-801/YM753, 5-FU, and radiation. Western blot analysis showed that OBP-801/YM753 suppressed the expression of thymidylate synthase induced by 5-FU. Therefore, this three-combined therapy is promising for patients with esophageal squamous carcinoma.

A case of severe chylothorax after esophagectomy successfully treated by a new combination of continuous positive-pressure ventilation plus chemical pleurodesis

Postoperative chylothorax is an uncommon but well-recognized and potentially life-threatening complication of esophagectomy for esophageal cancer. Its management remains controversial. A 71-year-old man with cancer of the thoracic esophagus was admitted to our hospital. A standard curative esophagectomy with extensive lymphadenectomy was performed. Two days after operation, chest roentgenography and computed tomography showed a massive right pleural effusion. A thoracic tube was placed in the right pleural cavity. The drainage volume of pleural effusion increased (up to 1500 ml/day), and chylothorax was diagnosed. Conservative drainage was continued for 4 days, but chyle leakage persisted. Minocycline hydrochloride 200 mg diluted in 50 ml saline was infused into the right pleural cavity through the tube to seal the leak. The patient concurrently received continuous positive-pressure ventilation (CPPV). The effusion completely resolved 30 h after beginning this combined treatment. To our knowledge, the treatment of chylothorax by CPPV plus chemical pleurodesis has not been reported previously in the English-language literature. Our method is simple, rapid, and may be a treatment option for patients with persistent chylothorax after esophagectomy that does not respond to conservative management or for patients in whom surgery is contraindicated.