A Case of Leiomyosarcoma Associated with Humoral Hypercalcemia of Malignancy: Demonstration of Biological and Immunological Activities of Parathyroid Hormone-related Protein in the Tumor Extract

Hypercalcemia occurred in a patient with leiomyosarcoma when multiple lung metastases developed. Despite normal plasma parathyroid hormone (PTH) levels and low 1,25-dihydroxyvitamin D, this hypercalcemic patient had a marked hypercakiuria and phosphatnria associated with an increased excretion of nephrogenous cyclic AMP (NcAMP). Administration of cisplatin ameliorated both the hypercalcemia and hypercalciuria without any reduction in tumor size or NcAMP excretion. Terminally, acute pancreatitis occurred producing a profound hypocalcemia. In the extract of tumor tissue obtained post mortem, bioactivity stimulating the generation of cyclic AMP in osteogenic cells was demonstrated along with the immunoreactive PTH-related protein (PTH-rP). This is the first report of a solid non-epithelial malignancy producing PTH-rP and associated with humoral hypercalcemia of malignancy. The hypercalcemia in this case caused acute pancreatitis, which led to a profound hypocalcemia     

Herbimycin A Suppresses the Reduction of Gap-junctional Intercellular Communication Induced by Tumor-promoting Phorbol Ester in 3T3-L1 Cells

We have examined the suppressive effect of herbimycin A on the reduction of gap-junctional Intercellular communication that is induced by a tumor-promoting phorbol ester in 3T3-L1 cells. Most cells in growth arrest participated in dye-coupling, as evaluated by the transfer between cells of a fluorescent dye (Lucifer Yellow CH). Treatment of cells with 0.25 μg/ml herbimycin A slightly enhanced the dye-coupling. This enhancement required treatment for periods as long as 24 h. Addition of 100 ng/ml 12-O-tetradecanoylphorbol-13-acetate (TPA) caused a rapid reduction of dye-coupling. However, addition of TPA did not suppress dye-coupling in cells pretreated for more than 24 h with herbimycin A. Pretreatment of cells for less than 6 h with herbimycin A did not suppress the TPA-induced reduction of dye-coupling. These results suggest that herbimycin A suppresses the reduction of gap-junctional intercellular communication that is induced by TPA through enhancement of the ability of the cells to participate in gap-junctional intercellular communication     

MTHFR多态性对晚期胃癌患者化疗作用的预测研究

目的:研究亚甲基四氢叶酸还原酶(MTHFR)基因C677T、A1298C多态与胃癌患者对5-FU为基础的化疗敏感性和毒性的关系。方法:晚期胃癌患者106例,用聚合酶链反应-限定性片段长度多态性(PCR-RFLP)技术检测白细胞DNAMTH-FR基因型。所有患者经5-FU为基础的化疗方案治疗。结果:1)在106例晚期胃癌患者中,MTHFRC677TCC、CT、TT基因型分别占31·1%、46·2%和22·6%;MTH-FRA1298CAA、AC、CC基因型者分别为69·8%、29·2%和0·9%;化疗总有效率35·8%。2)MTHFRC677TTT基因型携带者化疗有效率(83·3%)明显高于C677TCT(24·5%;P=0·000)和C677TCC(18·2%;P=0·000)。而MTHFRA1298CAA组有效率(43·2%)亦明显高于A1298CAC CC组(18·8%,P=0·009)。3)在CFL、CFH、LFP方案治疗的患者中,C677T变异子携带者对化疗敏感性更高。对A1298C多态性,患者接受CFL方案化疗时,1298AA纯合子携带者有效率高于1298CT/CC患者。4)MTHFRC677TTT、CT或A1298CAA多态性携带者化疗相关的恶心/呕吐发生率明显高于其他三种多态性者。结论:MTHFR基因多态性的检测可能是晚期胃癌患者接受5-FU为基础化疗疗效和毒副反应的良好预测指标。     

Ketoacidosis,Hypertriglyceridemia and Acute Pancreatitis Induced by Soft Drink Polydipsia in a Patient with Occult Central Diabetes Insipidus

A 21-year-old Japanese man without known diabetes mellitus had abdominal pain. The diagnosis was ketoacidosis and hypertriglyceridemia-induced acute pancreatitis. He had polydipsia and polyuria and had habitually drunk several soft drinks every day for two years. After hospitalization, despite adequate liquid intake, dehydration remained with hypotonic polyuria. Further examinations revealed the coexistence of central diabetes insipidus (CDI), possibly caused by lymphocytic infundibulo-neurohypophysitis, based on anti-rabphilin-3A antibody positivity. Although CDI had been undiagnosed for two years, over-consumption of sugar-rich soft drinks to ease thirst caused ketoacidosis, hypertriglyceridemia, and acute pancreatitis. There are no previous reports of this three-part combination of symptoms caused by CDI.     

Anticancer Activity of Novel NF-kB Inhibitor DHMEQ by Intraperitoneal Administration

There have been great advances in the therapy of cancer and leukemia. However, there are still many neoplastic diseases that are difficult to treat. For example, it is often difficult to find effective therapies for aggressive cancer and leukemia. An NF- B inhibitor named dehydroxymethylepoxyquinomicin (DHMEQ) was discovered in 2000. This compound was designed based on the structure of epoxyquinomicin isolated from a microorganism. It was shown to be a specific inhibitor that directly binds to and inactivates NF- B components. Until now, DHMEQ has been used by many scientists in the world to suppress animal models of cancer and inflammation. Especially, it was shown to suppress difficult cancer models, such as hormone-insensitive breast cancer and prostate cancer, cholangiocarcinoma, and multiple myeloma. No toxicity has been reported so far. DHMEQ was administered via the intraperitoneal (IP) route in most of the animal experiments because of its simplicity. In the course of developmental studies, it was found that IP administration never increased the blood concentration of DHMEQ because of the instability of DHMEQ in the blood. It is suggested that inflammatory cells in the peritoneal cavity would be important for cancer progression, and that IP administration, itself, is important for the effectiveness and safety of DHMEQ. In the present review, we describe mechanism of action, its in vivo anticancer activity, and future clinical use of DHMEQ IP therapy.