The genetic changes of cyclin A, DI, E and CDK2 were examined in human colorectal carcinomas by Southern-blot analysis. Gene amplification of cyclin E was detected in 5 of 53 (9.4%) primary colorectal carcinoma tissues. Interestingly, in 3 of 5 tumors showing cyclin E gene amplification, the CDK2 gene was amplified simultaneously with rearrangements. No obvious correlation was detected between gene amplification and clinicopathological features of colorectal carcinomas. Out of 7 colon carcinoma cell lines, 2 showed gene amplification of cyclin E without gene amplification of CDK2. No amplification of cyclin A or DI gene was found in any of the colorectal carcinoma tissues or colon carcinoma cell lines. Our results suggest that the concurrent amplification of cyclin E and CDK2 genes may play a role in colorectal carcinogenesis.

We measured expression of the MDR1 gene (also known as the PGY1 gene) in the human gastrointestinal tract. MDR1 messenger RNA (mRNA) levels were elevated in 13 of 15 colorectal carcinoma specimens and in six of 13 gastric carcinoma specimens. Well-differentiated colorectal carcinomas contained significantly higher concentrations of MDR1 mRNA than moderately differentiated colorectal carcinomas. Similarly, moderately differentiated gastric carcinomas contained higher concentrations of MDR1 mRNA than poorly differentiated gastric carcinomas. MDR1 gene expression in normal colorectal and gastric tissues adjacent to carcinomas was similar to that in the carcinomas. MDR1 gene expression in xenografts of colorectal and gastric carcinomas in nude mice was also investigated. Elevated expression of the MDR1 gene was seen in only four of 18 xenografts of colorectal carcinoma and was not seen in any xenografts of gastric carcinoma. P-glycoprotein was distributed over the luminal surface of the colorectal carcinoma. These results imply that the higher levels of MDR1 mRNA found in well-differentiated carcinomas derived from colorectal tissues are the results of increased expression of the MDR1 gene in the luminal surface cells. The level of expression of the MDR1 gene in colorectal and gastric carcinomas appears to correlate with the degree of differentiation and also appears to be affected by transplantation into nude mice.

In this study, the ability of granulocyte colony-stimulating factor (G-CSF) to treat or prevent chemotherapy-induced oral mucositis in patients with advanced breast cancer was evaluated. A total of 14 patients who received intraarterial (i.a.) adriamycin (ADM) preoperatively were divided into two groups according to whether or not G-CSF was given. Thus, group A (n = 7) was given G-CSF and group B (n = 7) was not. G-CSF therapy reduced both the incidence and duration of ADM-induced oral mucositis, and a positive correlation was also seen between the incidence of mucositis and ADM-induced leukopenia (< 2,000/mm3). Group A was further divided into two subgroups according to whether G-CSF was given after or before the leukopenia had dropped below 2,000/mm3: group A-1 (n = 3) and group A-2 (n = 4), respectively. ADM-induced mucositis was observed in two of the three patients in group A-1, but in none of the four patients in group A-2. These results strongly support the idea that G-CSF can effectively treat and prevent ADM-induced oral mucositis.

We experienced a case of blue rubber bleb nevus syndrome with familial onset. The patient was a 32-year-old male with a gallstone and many bluish rubber bleb-like hemangiomas on the skin. He suffered from repeated rectal bleeding and underwent a sigmoidectomy at age 17. Gastrointestinal hemangiomas were recognized in the esophagus, stomach, ileum and colon. An angiogram revealed multiple small poolings in the liver, suggesting the presence of hemangiomas. During the cholecystectomy, surgeons noted the presence of hemangiomas on the surface of the liver, serosa of the small intestine and retroperitoneum. Out of 73 blood relatives, 24 also had bluish skin hemangiomas, suggesting them to be inherited by an autosomal dominant trait. More than sixty cases of this syndrome had been reported in the world, eight of which had family histories of skin lesions. However, in only three cases, including our own, was the presence of skin and gastrointestinal hemangiomas recognized. Because the clinical indications for diagnosis of blue rubber bleb nevus syndrome consist of minimal to massive bleeding from the gastrointestinal tract, the possibility that this syndrome is present should be considered when diagnosing a bleeding patient with multiple bluish rubber bleb-like skin lesions, in addition to taking a detailed family history.

The dissolving mixture is administered through a choledochal drain to treat postoperatively retained cholesterol gallstones. It is prepared by mixing 97.0 parts of d-limonene with 2.1 parts of polysorbate 80 and 0.9 part of sorbitan monooleate, a mixture of which may easily reach the surface of the gallstones which are wetted by bile. The d-limonene preparation was found to be safe both in laboratory experiments and clinical trials. Before applying the preparation, the usual choledochal drain must be replaced with a recently developed catheter made from epichlorohydrine rubber, which is chemically resistant to the preparation. Three cases of retained gallstones are described where the preparation was successfully used. In the fourth case treatment with the preparation was tried in lieu of surgery but was not successful due to other complications. However, some dissolution of retained stones was observed. There were no postoperative complaints in the long-term follow-up of some cases for more than 2 yr after treatment with the preparation. This procedure promises to be of value because retained cholesterol stones may be dissolved without the necessity of further surgery.