Antitumor effects of soybean hypocotyls and soybeans on the mammary tumor induction by N-methyl-n-nitrosourea in F344 rats.

BACKGROUND: Soybeans are reported to have cancer inhibitory effects, probably due to their isoflavones. Soybean hypocotyls are embryo buds of soybeans and contain a higher amount of isoflavones and other factors than soybeans themselves. MATERIALS AND METHODS: The effects of soybean protein and soybean hypocotyls as diets on the development of N-methyl-n-nitrosourea (MNU) induced tumors were examined in female F344 rats. For this trial, 120 animals were used and at 6 weeks of age, groups of 30 animals were fed diets containing casein, soy protein isolate (SPI), 1.5% soybean hypocotyls and 5% soybean hypocotyls. Three weeks later all the animals except the control animals received a first dose (37.5 mg/kg body weight) of MNU by tail vein injection. At 29 weeks of age the animals received a second MNU dose (50 mg/kg body weight). Testing was performed 42 weeks after the first MNU dose. RESULTS: Analysis of cumulative palpable tumor incidence indicated that final tumor development of the SPI diet group and the hypocotyl diet groups was less than that of the casein diet group. Tumors were detected in one or more sites from 9 out of 24 rats in the casein diet group, 5 of 20 rats in SPI diet group, 6 out of 24 rats in the 1.5% hypocotyl diet group and 6 out of 23 rats in the 5% hypocotyl diet group. Pairwise comparisons indicated that the formation of tumors during the experiment was significantly less rapid in the SPI diet group and the hypocotyl diet groups than the casein group. No difference in tumor promotion was observed between the SPI diet group and the soybean hypocotyl diet groups. CONCLUSION: Our results suggest that dietary soybeans and soybean hypocotyls are capable of suppressing tumor promotion.

A new analytical method for the detection of anti-tumor promoters using flow cytometry.

Flow cytometry analysis was applied to the measurement of Epstein-Barr virus (EBV) induction which is used as a short term assay for anti-tumor promoters. The data obtained by measurement with flow cytometry were parallel with those of the fluorescence microscopic method. Flow cytometry is rapid, quantitative and should be applicable for the EBV activating test.

The role of cellular motility in the invasion of human neuroblastoma cells with or without N-myc amplification and expression.

BACKGROUND/PURPOSE: Patients who have neuroblastomas with N-myc amplification that are extremely invasive and result in distant metastases tend to have a very poor prognosis. The authors reported previously that N-mycamplification and expression might be closely related to the invasiveness of human neuroblastoma cells. However, the role of cellular motility has not yet been clarified in the invasion of neuroblastoma cells. The aim of this study was, therefore, to elucidate the role of cellular motility in the invasion of neuroblastoma cells. METHODS: Six human neuroblastoma cell lines were used for an invasion assay in vitro using polycarbonate filters coated with basement membrane Matrigel. The amplification and expression of N-myc oncogene was examined by Southern and Northern blotting, respectively. The cellular motility was quantified by computerized image analysis on the morphology of cultured cells. RESULTS: IMR-32, GOTO, and DZ, all of which had N-myc amplification, showed a high degree of invasiveness and a high cellular motility, whereas NB-69 and SK-N-SH without N-myc amplification showed an extremely low degree of invasiveness and cellular motility. ST without N-myc amplification, which was established from an aggressive tumor, showed an exceptionally high degree of motility and invasiveness. A transcriptional reduction of the N-myc gene by retinoic acid (RA) decreased the motility, which thus resulted in a marked decline of invasiveness in IMR-32 and GOTO. CONCLUSION: The cellular motility correlated with the invasive capacity of human neuroblastoma cells, which thus indicated that cellular motility may play an important role in invasion.

Bilateral adrenal neuroblastoma.

Neuroblastoma has been recognized as the most common solid tumor of infancy and childhood. The occurrence of bilateral adrenal neuroblastoma, however, is extremely rare and only a small number of cases have been previously reported. The authors herein report the clinical, histopathological and molecular biological features of two bilateral adrenal cases out of 125 neuroblastoma patients treated at Kyushu University Hospital over a 35-year period. The clinical and histopathological data of the two cases of bilateral adrenal neuroblastoma were reviewed. In Case 1, which had multiple liver metastases, a post-mortem examination revealed bilateral adrenal involvement. In Case 2, which had been detected by mass screening, CT showed masses in both adrenal glands. No big differences in size were recognized between the tumors in either of the cases. A histopathological examination revealed rosette fibrillary type neuroblastomas in both cases. The DNA of these tumor samples stored at -80 degrees C was extracted and the number of copies of the N-myc gene was determined by a Southern blot analysis. Fourteen copies of the gene were detected in Case 1, whereas neither of the tumors in Case 2 showed any amplification. The clinical outcome, histopathological findings and N-myc gene analysis of two cases might support the variety of biological features of this rare group of neuroblastoma.

Acute suppurative perithyroiditis: MR findings.

We report the MR findings in two cases of acute suppurative perithyroiditis. MR has the advantages over other imaging modalities of being able to distinguish areas of inflammation from adjacent normal tissue and of allowing imaging in planes which more accurately demonstrate the extent of the lesion. MR imaging is one of the most useful methods to evaluate this entity.

Surgical strategy for the treatment of pyriform sinus fistula.

Pyriform sinus fistula recurs when a complete excision of the fistula has not been made. As a supportive technique for this radical operation, the authors performed an intraoperative endoscopic examination of the pyriform sinus for the cannulation or dye injection of the tract in four cases. In three cases, the sinuses were relatively long and ran outside the thyroid cartilage. The cannulation of the tract with a guide wire, in these cases, was useful for identifying the thin membranous tract. In one of these three cases sinus fistula recurred, but a complete excision of the tract was then performed by introducing a 10F Nelaton catheter over a guide wire, which allowed for easy handling of the remnant tract. In the remaining case, cannulation proved not to be useful because the tract was short and ran inside the thyroid cartilage. A short tract embedded within the inferior constrictor muscle could only be found through careful observation after repeated dye injections. The proper selection of the optimum supportive techniques as described above, are considered to be essential for performing a complete excision.

Inhibitory effect of soybean hypocotyls on Epstein-Barr virus early antigen induction and skin tumor promotion.

The in vitro anti-tumor promoting effect of hypocotyls from fresh soybeans was evaluated. The dimethyl sulfoxide extracts of hypocotyls showed a stronger inhibitory effect than that of soybeans on Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate. Daidzin, an isoflavone with the highest content of hypocotyls, was also inhibitory. An in vivo evaluation of anti-tumor promoting activity of hypocotyls against the skin of mice also revealed a significant inhibitory effect on tumor formation.

Mass screening for neuroblastoma: quo vadis? A 9-year experience from the Pediatric Oncology Study Group of the Kyushu area in Japan.

Since 1985, a nationwide program of mass screening for neuroblastoma has been available for 6-month-old infants throughout Japan. From 1985 to 1993, the authors studied 285 patients with neuroblastoma among their regional population of 15 million. There was an increase in the total number of patients per year in comparison to the previous 6-year period (1979 to 1984). However, no significant difference was noted in the number of patients older than 1 year or in the incidence of advanced-stage (stages III and IV) unscreened cases. The majority of neuroblastomas in the screened group showed favorable biological factors, even in the advanced stages. However, there was a small group with histologically and/or biologically unfavorable factors; five of 115 had amplified N-myc oncogene, four of 74 showed unfavorable Shimada histological findings, and three of 33 had an unfavorable DNA ploidy pattern. One case from this group with unfavorable factors died of the tumor. 3) Thirty-eight cases were negative at the time of mass screening, but later presented with neuroblastoma. Most of them were diagnosed between 1 and 3 years of age, and 30 of the 38 cases (78.9%) were advanced stage with unfavorable prognostic factors. Thus, the authors conclude that mass screening at 6 months can detect a selected population of infants with neuroblastoma; some of the tumors may represent subclinical masses destined for spontaneous regression. However, some tumors with unfavorable factors have been detected by mass screening before progression and/or dissemination. Infants in this group are considered to benefit most from early diagnosis and treatment.

CT manifestations of pediatric intrathoracic desmoid tumors.

We describe the CT findings in two pediatric cases of intrathoracic desmoid tumor arising from the chest wall. In both cases, CT showed heterogeneously enhanced intrathoracic masses with destruction of the ribs.

Growth hormone effects on wound healing in malnourished animals: a histological study.

Systemic growth hormone (GH) markedly improves celiotomy wound strength in protein malnourished (PM) animals. This study was undertaken to analyze the effect of GH as a basis for anatomically understanding. Adult female Spraque-Dawley rats were divided into normally nourished controls, PM and GH-treated PM groups. Protein malnutrition was achieved by feeding 5.5% protein restricted chow every other day for eight weeks before surgery. Controls were fed 23.4% protein chow. All animals were fed 23.4% protein chow postoperatively. Rat-GH was injected subcutaneously twice daily (1.0 mg/day) for three days prior to and five days after 5 cm midline celiotomy. Bursting strength of the wound was measured at 3, 6 and 14 days postoperatively. Histologic wound specimens (hematoxylin and eosin) were obtained from each group. Wound strength of malnourished rats was significantly less than that of normal controls at six days after operation (p < 0.001). With administration of growth hormone, the wound strength was significantly improved. Histologically, there was no difference between groups on day 3. On day 6 the normal control group showed a decrease in the early inflammatory cell infiltrate with concurrent development of granulation tissue and a dense proliferation of fibroblasts. The PM wound showed fatty infiltration, a very narrow band of poorly formed granulation tissue and a sparse fibroblastic proliferation. The GH-treated PM group showed a combination of histologic findings. Fatty infiltration, similar to that in malnourished non-treated animals, was still evident but there was also a dense proliferation of capillary channels and fibroblasts comparable to normal animals.(ABSTRACT TRUNCATED AT 250 WORDS)

Juvenile xanthogranuloma of the pelvic origin: a case report.

A case of juvenile xanthogranuloma (JXG) originating from the pelvic cavity is reported. The patient, a 4-month-old girl, was referred to our department for the examination and treatment of her left abdominal mass. As radiological studies strongly suggested the possibility of a malignant tumor of muscular origin, tumor extirpation was performed. The tumor was buried in the left psoas muscle. Histological examination showed the tumor consisted of polygonal cells containing small vacuoles with scattered Touton giant cells, and the diagnosis of JXG was made. To our knowledge, this is the first case of a pelvic JXG.

Role of ultrasound in managing neuroblastoma detected by mass screening: a proposed ultrasonographic grading for children with neuroblastoma.

The ultrasonographic (US) findings of 25 infant cases detected by the Japanese mass screening program for neuroblastoma (NB) were reviewed. The following results were obtained: An identification of the primary site was possible in 96% of the cases with abdominal US. An estimation of the tumor weight was possible based on the mass volume, which was calculated from US measurements. With the combination of the estimated mass volume, local involvement, and distant metastasis, the US grading of NB was possible and closely corresponded to the surgical staging (84%). The NB cases of adrenal origin at U1a, with a mass volume of less than 16 mL, were all found to be stage I and presented the possibility for spontaneous regression.

Neuroblastoma in infants aged less than 6 months: is more aggressive treatment necessary? A report from the Pediatric Oncology Study Group of the Kyushu area.

Infants with neuroblastoma are known to have a better prognosis than older children. In Japan in 1985, mass screening for neuroblastoma in infants aged 6 months was introduced. With this policy, there has been an increase in the number of patients seen with neuroblastoma between 6 and 11 months of age. In a previous report the authors described the management and prognosis of infants with disease detected by mass screening, but there is still little information regarding the strategies of management for infants with neuroblastoma aged less than 6 months. The authors analyzed the data regarding 27 patients aged less than 6 months registered in their region (population 15 million) from 1985 to 1992, and compared it with that of the previous 8-year period. In the younger age group, there was a significantly higher rate of advanced disease stages (III and IV). In spite of the variation in treatment related to the choice of individual institutions, infants with stages I, II, and III disease had a good outcome, suggesting that aggressive chemotherapy is not necessary unless poor prognostic factors are present. One patient with stage IV disease died of disseminated disease and one with stage IVs and 22 copies of N-myc oncogene also died of tumor relapse in spite of aggressive chemotherapy. It is therefore concluded that the prognosis in infants with stage IV and IVs neuroblastoma under the age of 6 months is not as good as had previously been believed, and that such patients, therefore, require special consideration.

What is the benefit of aggressive chemotherapy for advanced neuroblastoma with N-myc amplification? A report from the Japanese Study Group for the Treatment of Advanced Neuroblastoma.

In 1985, a nationwide single protocol (cyclophosphamide, vincristine, tetrahydropyranyl Adriamycin, and cisplatin) for the treatment of advanced neuroblastoma was begun in Japan and was found to significantly increase the 3-year survival rate--to 70% for stage III, and to 45% for stage IV. In this study, the authors investigated the efficacy of this protocol for advanced neuroblastoma with or without N-myc amplification. In 159 of the 233 patients with advanced neuroblastoma treated with this protocol (between January 1985 and March 1993), genomic amplification of N-myc was determined. These 159 patients were divided into two groups according to the number of N-myc copies, ie, those with fewer than 10 copies (105 patients) and those with 10 or more copies (54 patients). The survival curves for the two groups were significantly different. The 5-year survival rate for patients with 10 or more copies was 43.9%; this is surprisingly high in comparison to results of previous studies in which no survivors were expected in cases of advanced neuroblastoma with highly amplified N-myc. Persistent bone marrow suppression was common, but there were no deaths attributable to drug side effects. Five patients with fewer than copies of N-myc amplification died more than 3 years after initial treatment. Three of the five had tumors with an unfavorable Shimada classification, and two had diploid nuclear DNA content. The authors conclude that the protocol resulted in dramatic improvement in the patients with advanced neuroblastoma, even with high N-myc amplification.(ABSTRACT TRUNCATED AT 250 WORDS)

How to deal with advanced cases of neuroblastoma detected by mass screening: a report from the Pediatric Oncology Study Group of the Kyushu area of Japan.

Since 1985, a nationwide program of mass screening (MS) for neuroblastoma has been underway for 6-month-old infants throughout Japan. As a result, the number of patients with stage I or II disease has obviously increased, and this has resulted in overall improvement of the prognosis for neuroblastoma. Some cases detected by MS were already in an advanced stage and have also had a good prognosis. In such cases, no definitive treatment protocol has been developed. Therefore, the authors investigated (1) the clinical and biological features of the advanced neuroblastoma cases detected by MS and (2) the best way to deal with such cases. The authors analyzed 94 cases of advanced-stage neuroblastoma registered in the Kyushu area (population, 15 million) between 1985 and 1990. Eighteen cases (16 stage III, 2 stage IV) were found by MS, and the others (23 stage III, 53 stage IV) were diagnosed clinically. The following results were obtained: (1) No N-myc amplifications were observed in cases detected by MS, whereas 16 of the 45 examined patients in the non-MS group had high amplifications of N-myc. (2) With regard to Shimada's classification, DNA content, and S-100 protein positivity, most of the advanced tumors found by MS showed characteristics indicating a good prognosis. (3) The 5-year survival rate for the non-MS group is less than 25%, whereas all of the patients whose tumors were detected by MS are alive, even after undergoing mild chemotherapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Retinoic acid induces insulin-like growth factor II expression in a neuroblastoma cell line.

Insulin-like growth factor II (IGF-II) is implicated in the development of the vertebrate neural circuitry, and increases neurite growth in vitro and in vivo. We examined the relationship of IGF-II expression to the in vitro differentiation induced by retinoic acid (RA). We find that RA stimulates an increase in IGF-II messenger RNA (mRNA) in the SK-N-SH (SH) neuroblastoma cell line. An increase of IGF-II mRNA is detected within 12 h of treatment and precedes morphological differentiation. A RA dose response test indicates that an increase in IGF-II mRNA occurs within 2 days in SH cells treated with doses of RA from 1 x 10(-8) to 1 x 10(-5) M. We suggest that IGF-II expression may be regulated either directly or indirectly by RA in vitro and may lead to neuroblastoma differentiation.

The effect of N-myc amplification and expression on invasiveness of neuroblastoma cells.

Most neuroblastomas with N-myc amplification, a sign of extremely poor prognosis, are extensively invasive to surrounding tissues. Therefore, we investigated the relationship between N-myc amplification and invasiveness of neuroblastoma cells, using an in-vitro assay system. Five human neuroblastoma cell lines were used for this study. IMR-32, GOTO, and DZ, all of which had N-myc amplification, showed a highly invasive capacity. In contrast, SK-N-SH without N-myc amplification showed extremely low invasiveness. ST unexpectedly showed high invasiveness in spite of the lack of N-myc amplification. Treatment of GOTO with 10(-5) mol/L all-trans-retinoic acid (RA) for 72 hours markedly decreased both N-myc expression and invasiveness. Treatment of GOTO with 2 mmol/L dibutyryl cyclic AMP (dbcAMP) for 72 hours caused a slight decrease of N-myc expression and invasiveness. These results indicate that N-myc amplification and expression might be closely related to the invasiveness of human neuroblastoma cells.

Undifferentiated (embryonal) sarcoma of the liver: report of three cases.

Undifferentiated (embryonal) sarcoma is a rare malignant tumor of the liver. It typically presents in late childhood and its prognosis is poor. We experienced three cases of such a tumor during the period of 1976-1989; two of these patients are still alive without disease. Each case was independently treated with a combination of surgery and pre- and/or postoperative chemotherapy, which was found to be effective. In one surviving patient, cyclophosphamide and vincristine were found to be effective, while in the other a combination of cisplatin, Adriamycin (ADM), vincristine and cyclophosphamide was observed to induce a rapid reduction in the size of the recurrent tumor. Thus, an adequate combination of surgery and chemotherapy may improve the prognosis of this tumor.

Establishment and characterization of a cell line of congenital primitive neuroectodermal tumor of soft tissue.

A new human cell line, termed Muraoka, has been established from the recurrent tumor of a case of congenital primitive neuroectodermal tumor (PNET) arising at the temporofacial region of a male infant. The microscopic findings of this cell line were epithelioid, and the xenografted tumor in a nude mouse consisted of the malignant epithelioid cells. Immunohistochemically, the cells were positive for neuron-specific enolase, S-100 protein, carcinoembryonic antigen, cytokeratin, epithelial membrane antigen, and glial fibrillary acidic protein. These findings were quite similar to those of the epithelioid cells in the original tumor and of the xenografted tumor cells. Neither chromosomal abnormalities nor N-myc amplification were observed. Morphological differentiation after treatment with N6-2'-O-dibutyryladenosine 3':5'-cyclic monophosphate (Bt2-cAMP), all-trans-retinoic acid (RA), prostaglandin E1 (PGE1), and 5-bromo-2'-deoxyuridine (BrdU) showed two different results. Bt2-cAMP and PGE1 induced neuronal differentiation with the extension of neurites, whereas RA and BrdU predominantly induced Schwannian differentiation (flat cells). In these respects, the cell line Muraoka seems to be useful for studying characteristics of PNET as well as for developing the new treatments against such tumors.