Nobuteru Kikkawa

CYP1A1 CYP2E1 and GSTM1 polymorphisms are not associated with susceptibility to squamous-cell carcinoma of the esophagus

We investigated the genetic polymorphisms of CYPIAI, CYP2EI and GSTMI in Japanese esophageal cancer patients (n = 53) with a histological diagnosis of squamous‐cell carcinoma, to determine whether susceptibility to esophageal cancer is associated with these polymorphisms. There were no significant differences in the frequency distribution of any one of the 3 polymorphisms between esophageal cancer patients and 132 healthy Japanese controls. The genotype distributions in tobacco smokers or alcohol drinkers were also quite similar for male patients and male controls. The age at onset of esophageal cancer was also similar for patients with any genotype of the 3 polymorphisms. We conclude that the 3 polymorphisms are unlikely to be associated with esophageal cancer susceptibility. Int. J. Cancer 71:192–195, 1997.

Midkine expression in human breast cancers : Expression of truncated form

The expression of midkine (MK), a growth/differentiation factor,was assessed in 34 surgically resected specimens ofprimary breast cancer or mastopathy. Using reverse transcriptase-polymerasechain reaction (RT-PCR) analysis, all of the non-cancerousand cancerous tissues were found to express MKexcept for one breast cancer specimen. Northern blotanalysis revealed that MK mRNA was also expressedin the normal breast tissues examined. Immunohistochemical analysisof the MK protein was performed on alimited number of the specimens, showing that somecancerous tissues were immunoreactive with anti-MK antibodies. Furthermore,using RT-PCR analysis, expression of not only thewild-type but also a truncated form of MK,which was recently found in various human tumorcell lines, was detected in 6 of 26cancerous tissues but not in non-cancerous tissues.

Molecular characteristics of poorly differentiated adenocarcinoma and signet-ring-cell carcinoma of colorectum

In a series of 45 poorly differentiated adenocarcinomas (por) and 7 signet‐ring‐cell carcinomas (sig) of the colorectum, K‐ras gene mutation, p53 immunostaining and microsatellite instability (MSI) were analyzed for a comparison with 46 cases of colorectal carcinomas of the well or moderately differentiated type (well/mod). In addition, the mutations of simple repeated sequences in the transforming‐growth‐factor‐β type‐II receptor (T β R‐II) gene and the BAX gene were analyzed as possible targets for DNA replication errors. Mutation of the K‐ras gene in the por, sig and well/mod specimens was detected in, respectively, 22%, 11% and 48%, positive immunostaining for p53 in 41.8%, 28.6% and 60.3%, and MSI in 36%, 30% and 4%. Frameshift mutation of the T β R‐II gene was detected in 27.5% of the por and none of the sig specimens, while corresponding figures for mutation of the BAX gene were 15.7% and 0%. Significant differences between the por and well/mod tumors were found in the occurrence of K‐ras mutation at codons 12 and 13, and MSI. Clinicopathologically, the tumor status of por with MSI was found to significantly correlate with the tumors location in the proximal colon. In cases without MSI and sig, no frameshift mutation of either the T β R‐II or the BAX gene was found. These results suggest that poorly differentiated and signet‐ring‐cell carcinomas have a genetic background different from that of well or moderately differentiated carcinomas of the colorectum, and that DNA‐replication error is at least partly involved in the carcinogenesis of these specific types of colorectal carcinomas. Int. J. Cancer (Pred. Oncol.) 84:33–38, 1999.

A new regimen for S-1 therapy aiming at adverse reaction mitigation and prolonged medication by introducing a 1-week drug-free interval after each 2-week dosing session: efficacy and feasibility in clinical practice.

BackgroundThe response rate of advanced or recurrent gastric cancer to S-1 (TS-1®) is 46.5%, which is higher than the response rate of this type of cancer to any other anticancer agent. However, the incidence of adverse reactions to this drug has also been reported to be as high as 83.2%. According to a postmarketing survey, adverse reactions to this drug begin to appear 2–3 weeks after the start of drug administration. With these findings in mind, we recently devised a new dosing regimen for the drug, by which the drug is administered for 2-week periods separated by 1-week drug-free intervals (the 2-week regimen). The aim of this retrospective study was to evaluate the efficacy and feasibility of the 2-week regimen in comparison with a 4-week dosing regimen with a 2-week interval between sessions (the 4-week regimen) as the historical control.MethodsThe subjects were 27 patients with advanced or recurrent gastric cancer who received S-1 therapy at our center between September 1999 and November 2001. Of these patients, 14 who received the 4-week regimen before January 2001 served as historical controls, and the results in these patients were compared with those of the remaining 13 patients, who received the 2-week regimen after February 2001. Patient backgrounds, adverse reactions, compliance, and efficacy were investigated retrospectively.ResultsThe incidence of adverse reactions tended to be lower in the 2-week-regimen group (77%) than in the 4-week-regimen group (93%). The percentage of patients who received the drug for 6 months in complete compliance with the dosing schedule, as calculated by the Kaplan-Meier method, was 85% in the 2-week-regimen group and 40% in the 4-week-regimen group. The response rate to the drug was 23% in the 2-week-regimen group and 21% in the 4-week-regimen group.ConclusionThese results suggest that this 2-week regimen may mitigate adverse reactions and prolong the medication period.

Metastatic breast cancer with resistance to both anthracycline and docetaxel successfully treated with weekly paclitaxel

Abstract We report the case of a 38-year-old woman who underwent surgery for stage III-b breast cancer, and whose liver metastasis failed to respond to both docetaxel (administered at 30–40 mg/m2 every 2 weeks as a 1-h intravenous infusion) and epirubicin (administered as a 40–60 mg/m2 bolus hepatic arterial infusion). For subsequent treatment, this patient was managed with weekly paclitaxel. The regimen showed some usefulness for the treatment of the liver metastasis, as indicated by an improvement in performance status and tolerable toxicity. This case demonstrates that weekly paclitaxel may be well tolerated and useful for patients with extensive metastatic breast cancer that was resistant to treatment. Our findings also suggest that paclitaxel could be used as a salvage therapy in patients with anthracycline- and docetaxel-resistant breast cancer.

Expression of truncated midkine in human colorectal cancers.

Midkine (MK) is a growth differentiation factor originally found as the product of a retinoic acid-responsive gene. The expression of MK was examined in 35 surgically resected specimens of primary colorectal cancer using the reverse transcription-polymerase chain reaction (RT-PCR). All of the cancerous tissues expressed MK. In 5/25 cancerous tissues a truncated form of MK, which was recently found in various human tumor cell lines, was detected in addition to the full-size MK. In contrast, the truncated from of MK could not be detected in non-cancerous tissues, whereas the wild-type form was detected in 8/10 non-cancerous tissues. These results suggest that the expression of the truncated form of MK may be associated with tumorigenesis.

New Technique of Laparoscopic-Assisted Excision of a Cholecystocolic Fistula: Report of a Case

Abstract Cholecystocolic fistula is a rare complication of gallstone disease that is most commonly diagnosed at the time of surgery. It is generally considered to be a contraindication to laparoscopic cholecystectomy because of the difficulties involved in its management intraoperatively. Laparoscopic stapling or suturing techniques have been reported as feasible and safe methods for repairing such fistulas; however, these procedures are not always able to be performed due to technical difficulties. We exteriorized a cholecystocolic fistula through an umbilical incision, whereby it was repaired safely and easily. This report describes our new technique for managing a cholecystocolic fistula found incidentally during a laparoscopic cholecystectomy.

A Case of Basal Cell Carcinoma of the Nipple and Areola with Intraductal Spread

We report an 82-year-old Japanese woman with basal cell carcinoma of the left nipple and areola extending into the lactiferous duct. The patient developed a small papular lesion of the left areola about 1 year before admission. The lesion, which had slowly progressed to involve the nipple, had become symptomatic showing weeping and bleeding. Mammography revealed microcalcification in the nipple. Although Paget’s disease was suspected from these clinical features, histologically basal cell carcinoma was diagnosed. There was no axillary lymphadenopathy, and no evidence of distant metastasis. The lesion of the nipple and areola was resected with a 2 cm free margin along with the underlying mammary tissue. The patient has remained well without signs of recurrence for 2 years after surgery. We reviewed cases of basal cell carcinoma of the nipple or areola and discuss considerations and problems of this rare tumor.

Down-regulation of drs mRNA in human colon adenocarcinomas

We have previously reported that the drs gene, whose mRNA expression is down‐regulated by retroviral oncogenes such as v‐src and v‐K‐ras, has the ability to suppress transformation by v‐src and v‐K‐ras in the rat cell line F2408. We have also isolated a human homolog of this gene (h‐drs) and shown that expression of h‐drs mRNA is markedly reduced in a variety of human cancer cell lines, including those of carcinomas of the colon, bladder, and ovary, suggesting that down‐regulation of drs mRNA is correlated with the development of human cancers. To clarify the correlation between down‐regulation of the drs gene and malignant tumor formation in human cancer tissues, we examined expression of drs mRNA in human normal tissues, colon adenoma, and adenocarcinoma tissues by in situ hybridization. Expression of drs mRNA was detected in most normal tissues tested, including those of the colon, bladder, and ovary. However, drs mRNA was hardly expressed in any of the colon adenocarcinoma tissues examined. Northern blot analyses confirmed these results. Neither gross deletion nor re‐arrangement of the drs genome was detected by Southern blot hybridization in these adenocarcinoma tissues. drs mRNA was significantly expressed in colon adenoma with mild atypia but down‐regulated in adenomas with moderate atypia and focal carcinoma. Our results indicate that down‐regulation of drs mRNA is closely correlated with development of colon adenocarcinoma, suggesting a tumor‐suppressor function of the drs gene in human cancers. Int. J. Cancer 87:5–11, 2000.

Hyperfunctioning intrathyroid parathyroid adenoma: Report of two cases

We report herein two cases of intrathyroid parathyroid adenoma, which is a rare condition in patients with hyperparathyroidism. In the first patient, an excised intrathyroid nodule was diagnosed to be parathyroid adenoma postoperatively. In the second patient, preoperative localization studies suggested the possibility of an intrathyroid adenoma. When a pathological gland is not found during surgery for primary hyperparathyroidism, an ectopic parathyroid gland including an intrathyroid adenoma should thus be considered.