TZT-1027, a dolastatin 10 derivative, is an antimicrotubule agent with potent antitumor activity both in vitro and in vivo. In this study, we performed biochemical and histopathological examinations, and evaluated TZT-1027-induced tumoral vascular collapse and tumor cell death in an advanced tumor model, murine colon 26 adenocarcinoma. In addition, we studied the effects of TZT-1027 on cultured human umbilical vein endothelial cells (HUVEC). Tolerable doses of TZT-1027 induced tumor-selective hemorrhage within 1 h. This hemorrhage occurred mainly in the peripheral area of the tumor mass. Measurements of tumoral hemoglobin content and dye permeation revealed that the hemorrhage occurred firstly and tumor blood flow stopped secondarily. The vascular damage was followed by continuous induction of apoptosis of the tumor cells, tumor tissue necrosis, and tumor regression. In cultured HUVEC, TZT-1027 induced marked cell contraction with membrane blebbing in 30 min. These cell changes were completely inhibited by K252a, a broad-spectrum inhibitor of protein kinases. These effects of TZT-1027 on both tumor vasculature and HUVEC were greater than those of vincristine. In conclusion, TZT-1027 quickly attacked the well-developed vascular system of advanced tumors by a putative protein kinase-dependent mechanism, and then blocked tumor blood flow. Therefore, TZT-1027 has both a conventional antitumor activity and a unique anti-tumoral vascular activity, making it a potentially powerful tool for clinical cancer therapy.

Inflammatory pseudotumor (IPT) is a rare benign condition often misdiagnosed as malignancy. An 80-year-old man was referred to our clinic for an asymptomatic hepatic mass detected on plain abdominal CT. Abdominal ultrasonography identified the lesion as a poorly defined hypoechoic mass. Although a liver biopsy did not provide any evidence of malignancy, imaging modalities suggested a diagnosis of cholangiocarcinoma. The patient underwent left lobectomy, and the pathological findings were consistent with the features of xanthogranulomatous cholangitis. This case is the first report of hepatic IPT originating from xanthogranulomatous cholangitis without symptoms and illustrates the importance of obtaining a preoperative diagnosis in order to avoid a misdiagnosis of malignant tumor.

Skin atrophy is one of the senile changes of the human body. In the histological pictures of the atrophied skin, we notice a thinning of the epithelial layer, a disappearing of papillae, a flattening of the basal layer, a diminishing of capillaries, especially in papillae, a degeneration and disappearance of elastic fibers in papillae and cutis, etc.Both Ogata and Takixawa, in considering the relationship between senile changes and asialadenism, acknowledge in their experimental studies on salivary glands, an important role of decreasing endocrine function of the salivary glands, resulting in the appearance of senile skin atrophy.It may be of some interest to know the effects of Parotin, i.e. the hormone of the salivary glands, on this senile skin atrophy.In an experiment on a human body which was made possible through the willingness of an aged gentleman, we had the opportunity of observing the effects of the Parotin supplement to the atrophied skin.