MicroRNA-143-3p Inhibits Wilms' Tumor Cell Growth By Targeting the Ras/Raf/MEK/ERK Pathway.

Background: A previous study found that microRNA-143-3p (miR-143-3p) is a tumor suppressor in various types of human cancer. However, the roles and molecular mechanisms of miR-143-3p in the progression of Wilms' tumor (WT) remain to be clarified. The aim of the present study was to determine the expression and biological functions of miR-143-3p in WT. Material and Methods: The expression levels of miR-143-3p in primary WT tissues and adjacent tissues were determined using quantitative-reverse transcription polymerase chain reaction (qRT-PCR), and the association of the miR-143-3p expression level with various clinicopathological features of WT was investigated. Western blotting was used to evaluate the protein expression of the related signaling pathway. Results: The expression of miR-143-3p was significantly downregulated in WT tissues and its expression levels were closely associated with tumor stage and lymph node metastasis. Overexpression of miR-143-3p in SK-NEP-1 and G401 cell lines inhibited cell proliferation by G0/G1 cell cycle phase arrest and induction of apoptosis. Moreover, k-Ras, a unique oncogene, was confirmed as a direct target of miR-143-3p, and k-Ras messenger RNA (mRNA) expression was increased in WT tissues and inversely correlated with miR-143-3p. Knockdown of k-Ras by si-k-Ras could inhibit, whereas overexpression of k-Ras could promote. cell proliferation in WT cells. Meanwhile, overexpression of k-Ras reversed the inhibitory effects on WT cells induced by miR-143-3p mimics. Conclusion: Our findings indicate that miR-143-3p may be a potential novel prognostic biomarker and therapeutic target for WT.

Suprahepatic Cava Thrombus Due to Wilms Tumor: Technique Without Cardiopulmonary Bypass.

Wilms tumor is a frequent malignant neoplasia in pediatric population. Extension to the inferior vena cava is a complication that occurs in approximately 4%-15% of cases. Surgical techniques derived from the field of adult transplant surgery allow the resection of the tumor with its thrombus extension. In the case of a 6-year-old male patient with a stage III Wilms tumor that originated from the left renal vein, thrombectomy and left radical nephroureterectomy were accomplished without extracorporeal circulation. Surgical technique applied in adult transplant surgery for removal of advanced renal tumors, could be a safe and feasible technique in pediatric population.

Maternal lifestyle characteristics and Wilms tumor risk in the offspring: A systematic review and meta-analysis.

BACKGROUND: Little is known about the etiology of childhood Wilms tumor (WT) and potentially modifiable maternal risk factors, in particular. METHODS: Unpublished data derived from the hospital-based, case-control study of the Greek Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM-ST) were included in an ad hoc conducted systematic literature review and meta-analyses examining the association between modifiable maternal lifestyle risk factors and WT. Eligible data were meta-analysed in separate strands regarding the associations of WT with (a) maternal folic acid and/or vitamins supplementation, (b) alcohol consumption and (c) smoking during pregnancy. The quality of eligible studies was evaluated using the Newcastle-Ottawa Scale. RESULTS: Effect estimates from 72 cases and 72 age- and sex-matched controls contributed by NARECHEM-ST were meta-analysed together with those of another 17, mainly medium size, studies of ecological, case-control and cohort design. Maternal intake of folic acid and/or other vitamins supplements during pregnancy was inversely associated with WT risk (6 studies, OR: 0.78; 95 %CI: 0.69-0.89, I2 = 5.4 %); of similar size was the association for folic acid intake alone (4 studies, OR: 0.79; 95 %CI: 0.69-0.91, I2 = 0.0 %), derived mainly from ecological studies. In the Greek study a positive association (OR: 5.31; 95 %CI: 2.00-14.10) was found for mothers who consumed alcohol only before pregnancy vs. never drinkers whereas in the meta-analysis of the four homogeneous studies examining the effect of alcohol consumption during pregnancy the respective overall result showed an OR: 1.60 (4 studies, 95 %CI: 1.28-2.01, I2 = 0.0 %). Lastly, no association was seen with maternal smoking during pregnancy (14 studies, OR: 0.93; 95 %CI: 0.80-1.09, I2 = 0.0 %). CONCLUSIONS: In the largest to-date meta-analysis, there was an inverse association of maternal folic acid or vitamins supplementation with WT risk in the offspring, derived mainly from ecological studies. The association with maternal alcohol consumption found in our study needs to be further explored whereas no association with maternal smoking was detected. Given the proven benefits for other health conditions, recommendations regarding folic acid supplementation as well as smoking and alcohol cessation should apply. The maternal alcohol consumption associations, however, should be further explored given the inherent limitations in the assessment of exposures of the published studies.

Maternal and perinatal characteristics, congenital malformations and the risk of wilms tumor: the ESTELLE study.

PURPOSE: Wilms tumor (WT), or nephroblastoma, is an embryonic tumor that constitutes the most common renal tumor in children. Little is known about the etiology of WT. The aim of this study was to investigate whether maternal or perinatal characteristics were associated with the risk of WT. METHODS: The ESTELLE study is a national-based case-control study that included 117 cases of WT and 1,100 controls younger than 11 years old. The cases were children diagnosed in France in 2010-2011 and the controls were frequency matched with cases by age and gender. The mothers of case and control children responded to a telephone questionnaire addressing sociodemographic and perinatal characteristics, childhood environment, and lifestyle. Unconditional logistic regression models adjusted on potential cofounders were used to estimate the odds ratios (OR) and their confidence intervals (95% CI). RESULTS: High birth weight and the presence of congenital malformation were associated with WT (OR 1.9 [95% CI 1.0-3.7] and OR 2.5 [95% CI 1.1-5.8], respectively). No association with breastfeeding or folic acid supplementation was observed. CONCLUSIONS: Although potential recall bias cannot be excluded, our findings reinforce the hypothesis that high birth weight and the presence of congenital malformation may be associated with an increased risk of WT. Further investigations are needed to further elucidate the possible role of maternal characteristics in the etiology of WT.

The antitumor effect of static and extremely low frequency magnetic fields against nephroblastoma and neuroblastoma.

Certain magnetic fields (MF) have potential therapeutic antitumor effect whereas the underlying mechanism remains undefined. In this study, a well-characterized MF was applied to two common childhood malignancies, nephroblastoma and neuroblastoma. This MF has a time-averaged total intensity of 5.1 militesla (mT), and was generated as a superimposition of a static and an extremely low frequency (ELF) MF in 50 Hertz (Hz). In nephroblastoma and neuroblastoma cell lines including G401, CHLA255, and N2a, after MF exposure of 2 h per day, the cell viability decreased significantly after 2 days. After 3 days, inhibition rates of 17-22% were achieved in these cell lines. Furthermore, the inhibition rate was positively associated with exposure time. On the other hand, when using static MF only while maintaining the same time-averaged intensity of 5.1 mT, the inhibition rate was decreased. Thus, both time and combination of ELF field were positively associated with the inhibitory effect of this MF. Exposure to the field decreased cell proliferation and induced apoptosis. Combinational use of MF together with chemotherapeutics cisplatin (DDP) was performed in both in vitro and in vivo experiments. In cell lines, combinational treatment further increased the inhibition rate compared with single use of either DDP or MF. In G401 nephroblastoma tumor model in nude mice, combination of MF and DDP resulted in significant decrease of tumor mass, and the side effect was limited in mild liver injury. MF exposure by itself did not hamper liver or kidney functions. In summary, the antitumor effect of an established MF against neuroblastoma and nephroblastoma is reported, and this field has the potential to be used in combination with DDP to achieve increased efficacy and reduce side effects in these two childhood malignancies. Bioelectromagnetics. 39:375-385, 2018. © 2018 Wiley Periodicals, Inc.

Initial testing (stage 1) of the topoisomerase II inhibitor pixantrone, by the pediatric preclinical testing program.

Pixantrone, a novel aza-anthracenedione with cytotoxic activity, was tested against the PPTP in vitro panel (3.0 nM to 30.0 µM) and against a limited panel of PPTP Wilms tumors and sarcomas (7.5 mg/kg) administered intravenously using an every 4 day × 3 schedule. In vitro pixantrone showed a median relative IC50 value of 54 nM (range <3 nM to 1.03 µM). In vivo pixantrone induced significant differences in EFS distribution compared to controls in two of eight solid tumor xenografts at dose levels relevant to human drug exposure. A complete response was observed for one Wilms tumor xenograft.

Berberine inhibits Wilms' tumor cell progression through upregulation of Wilms' tumor gene on the X chromosome.

Wilms' tumor is a type of kidney cancer that affects young children. Although a number of Wilms' tumor samples have been collected through international trials, the mechanisms underlying its progression remain challenging to determine. Extensive studies have identified somatic mutations at several loci in Wilms' tumorigenesis, including WT1, catenin, Wilms' tumor gene on the X chromosome (WTX) and TP53. Berberine is a benzylisoquinoline alkaloid extracted from numerous types of medicinal plants and has been extensively used as a Chinese traditional medicine. Recently, berberine has been demonstrated to possess antitumoral activities. AMP-activated protein kinase (AMPK) is suggested to be one of the various cellular targets of berberine, which regulates tumor progression and metastasis. However, the specific involvement of berberine­induced AMPK activation and its effects on the proliferation potential of Wilms' tumor cells remains unknown. The present study investigated the berberine­induced activation of AMPK and its effects on G401 Wilms' tumor cell proliferation. The results demonstrated that berberine inhibited growth and decreased the expression of cell­cycle regulators in these cells. At the molecular level, berberine treatment led to a significant increase of WTX expression and G401 cells were protected against berberine­induced growth inhibition by small interfering RNA against WTX. In conclusion, these results suggest a novel mechanism that may contribute to the antineoplastic effects of berberine which was also demonstrated by recent population studies; however, further studies are required to investigate the potential therapeutic use of berberine in patients with Wilms' tumor.

Molecular characterization of Wilms' tumor from a resource-constrained region of sub-Saharan Africa.

Sub-Saharan African children have an increased incidence of Wilms' tumor (WT) and experience alarmingly poor outcomes. Although these outcomes are largely due to inadequate therapy, we hypothesized that WT from this region exhibits features of biological aggressiveness that may warrant broader implementation of high-risk therapeutic protocols. We evaluated 15 Kenyan WT (KWT) for features of aggressive disease (blastemal predominance and Ki67/cellular proliferation) and treatment resistance (anaplasia and p53 immunopositivity). To explore the additional biological features of KWT, we determined the mutational status of the CTNNB1/ß-catenin and WT1 genes and performed immunostaining for markers of Wnt pathway activation (ß-catenin) and nephronic progenitor cell self-renewal (WT1, CITED1 and SIX2). We characterized the proteome of KWT using imaging mass spectrometry (IMS). The results were compared to histology- and age-matched North American WT (NAWT) controls. For patients with KWT, blastemal predominance was noted in 53.3% and anaplasia in 13%. We detected increased loss to follow-up (p = 0.028), disease relapse (p = 0.044), mortality (p = 0.001) and nuclear unrest (p = 0.001) in patients with KWT compared to controls. KWT and NAWT showed similar Ki67/cellular proliferation. We detected an increased proportion of epithelial nuclear ß-catenin in KWT (p = 0.013). All 15 KWT specimens were found to harbor wild-type CTNNB1/ß-catenin, and one contained a WT1 nonsense mutation. WT1 was detected by immunostaining in 100% of KWT, CITED1 in 80% and SIX2 in 80%. IMS revealed a molecular signature unique to KWT that was distinct from NAWT. The African WT specimens appear to express markers of adverse clinical behavior and treatment resistance and may require alternative therapies or implementation of high-risk treatment protocols.

A retrospective study of the preoperative treatment of advanced Wilms tumor in children with chemotherapy versus transcatheter arterial chemoembolization alone or combined with short-term systemic chemotherapy.

PURPOSE: To evaluate the therapeutic effect of preoperative transcatheter arterial chemoembolization (TACE) combined with short-term systematic chemotherapy in the treatment of advanced Wilms tumor. MATERIALS AND METHODS: This was a retrospective study on 66 patients with unilateral advanced Wilms tumor, age 5 months to 11 years (median, 2.9 years; 30 boys and 36 girls), treated at our institution between 1995 and 2007. Characteristics of the patient population were maximal tumor diameter > 10 cm, or involvement of periaortic lymph nodes, or inferior vena cava invasion, or distal metastasis, or tumor with anaplastic histology. Patients were divided into three groups. Twenty patients were treated with conventional preoperative chemotherapy (PC group) using vindesine, actinomycin D, and pirarubicin for 4 weeks; 21 patients were treated in the TACE group with preoperative renal arterial chemoembolization using Lipiodol-pirarubicin-vindesine emulsion; and 25 patients were treated with preoperative chemoembolization combined with short-term systematic chemotherapy (T+S) for 2 weeks. RESULTS: No drug-induced cardiotoxicity, nephrotoxicity, or hepatic dysfunction was observed. Complete surgical removal of the tumor was achieved in 12 (65.0%), 17 (80.9%), and 22 (88.0%) patients in the PC, TACE, and T+S groups, respectively (T+S group vs PC group, P = .030). The 2-year relapse-free survival rates were 65.0%, 80.9%, and 100.0% in the PC, TACE, and T+S groups, respectively (T+S vs PC, P = .001). CONCLUSIONS: From our experience, preoperative chemoembolization combined with short-term systematic chemotherapy is able to achieve higher rates of complete tumor resection and relapse-free survival in the treatment of advanced Wilms tumor.

[Treatment of advanced Wilms' tumor].

OBJECTIVE: To improve prognosis of the patients with advanced Wilms' tumor, the authors compared different therapeutic strategies including preoperative transcatheter arterial chemoembolization (TACE), conventional preoperative chemotherapy and initial surgery. METHODS: Sixty-two patients aged from 5 months to 10 years (mean 3.2 years) were identified from medical records to have histologically confirmed advanced Wilms' tumor during the period from January 1993 to December 2002. The criteria for choice were huge tumor size with a volume more than 550 ml or the mass extending beyond the midline, involvement of vital structures, inferior vena cava invasion, distal metastasis or bilateral Wilms' tumor judged by imaging examination. All cases were divided into 3 groups according to the treatment received: 31 cases in group TACE received preoperative transcatheter arterial chemoembolization with Lipiodol-Epirubicin (EPI)-Vincristine emulsion. One week after TACE, systemic chemotherapy with Actinomycin D (ACTD) was administered and tumor resected at two weeks after TACE. 20 cases in group PC received conventional preoperative chemotherapy with VCR, ACTD plus EPI for 4-5 weeks, and 11 cases in group IS underwent initial surgery. Postoperative treatment for all patients was based on the postoperative staging and tumor histology. RESULTS: In the patients treated with TACE, no drug-induced complications such as cardiotoxicity, nephrotoxicity, hepatic dysfunction or bone marrow suppression were observed except for mild fever due to tumor necrosis. The percentages of tumor size shrinkage were 32.4% and 20.3% in group TACE and group PC, respectively (P < 0.05). Complete surgical removal of the tumor was achieved in 27 patients (87.1%) in group TACE, significantly higher in comparison with 14 in group PC (70.0%, P < 0.05) and 2 in group IS (18.2%, P < 0.01). Event-free survival (EFS) at 2 years was 87.1% (27/ 31), 60.0% (12/20) and 18.2% (2/11), respectivrely. EFS at 4 years was 84.6% (11/13), 56.3% (9/16 ) and 18.2% (2/11) in groups TACE, PC and IS, respectively. CONCLUSION: The present study has shown that both preoperative TACE and conventional preoperative chemotherapy can be applied to the patients with advanced Wilms' tumor who are not candidates for immediately surgical resection. The survival is significantly increased in the patients undergoing preoperativeTACE when compared with conventional preoperative chemotherapy and initial surgery.

Eel WT1 sequence and expression in spontaneous nephroblastomas in Japanese eel.

Nephroblastomas spontaneously developing in Japanese eel reared at farms for 5 to 9months after collection from the wild [Masahito et al., Cancer Res., 52 (1992) 2575-2579] were investigated to cast light on the role of Wilms' tumor 1 gene (WT1) in eel kidney tumorigenesis. Cloning of the WT1 counterpart, EWT1, revealed that conservation of an alternative splice II site, located between the third and fourth zinc fingers, was conserved. The zinc finger domain was highly conserved. The transregulator region, sequences corresponding to exons 4 and 5 in WT1, were lacking in EWT1 cDNA. EWT1 was found to be expressed in kidney, testis and spleen and in situ hybridization revealed dark-stained immature cells in elver kidney to be positive. Although no EWT1 gene mutations were found in 38 eel nephroblastomas, 26 polymorphic nucleic acid changes were observed. Aberrant WT1 expression was noted in epithelial (12 out of 27; 44%) and nephroblastic cell histological types (three out of five; 60%) of eel nephroblastomas. On in situ hybridization the EWT1 expressive cells resembled human blastema cells, similar to those in human Wilms' tumor. These data demonstrated strong signals that the EWT1 protein may function in the development of eel kidney and play a role in genesis of nephroblastomas as in mammals.

Long-term outcome of acute renal injury induced by Aristolochia manshuriensis Kom in rats.

AIM: To investigate the long-term functional and morphological changes of the kidney induced by acute intoxication of Aristolochia manshuriensis Kom in rats. METHODS: Experimental model of acute renal injury was established in the Sprague-Dawley rats with oral administration of decoctions of Chinese herb, Aristolochia manshuriensis Kom, at dosages of 50 g.kg-1.d-1 and 30 g.kg-1.d-1 for 7 consecutive days, and 20 g.kg-1.d-1 for 15 consecutive days. Renal function was assayed at months 0 (right after treatment), 1, 3, and 6 of the experiment. Renal histological examination was also performed. RESULTS: 1) At month 0, the renal functional changes of acute renal injury included azotemia, low molecular weight proteinuria, glycosuria, hypoosmotic urine, and NAG enzymuria. Histopathological changes showed acute tubular necrosis, predominantly at the corticomedullary junction. 2) At months 1 and 3, the renal function of rats of the experiment was gradually restored and histopathologic examination suggested that the tubular lesions gradually recovered. In HE sections, basophilic deposits were observed in the tubular cytoplasm. And interstitial infiltration of inflammatory cells was not prominent. 3) At months 6, renal preneoplastic lesions, renal tumors, and extrarenal tumors occurred in rats. The occurrence of renal preneoplastic lesions at dosages of 50 g.kg-1.d-1, 30 g.kg-1.d-1, and 20 g.kg-1.d-1 were 100.0% at all three doses, renal tumors 42.8%, 25.0%, and 0%, respectively, extrarenal tumors 14.4%, 12.5%, and 12.5%, respectively, and systemic tumors 57.2%, 37.5%, and 12.5%, respectively. The occurrence of basophilic deposits, renal preneoplastic lesions, renal tumors, and extrarenal tumors in normal control group was nil. CONCLUSIONS: 1) Administration of large dosage of Aristolochia manshuriensis Kom induces acute renal failure in rats. 2) The long-term renal function and histopathologic changes of acute renal injury induced by Aristolochia manshuriensis Komrecover spontaneously. 3) Aristolochia manshuriensis Kom has been proved to be oncogenic for the first time.

Effect of hyperthermia 42.5 degrees C/120 min on 3H-thymidine incorporation in different tissue components of Wilms' tumors: an in vitro study.

BACKGROUND: Survival rates of Wilms' tumors are correlated to tumor histology. Clinical studies and histological investigations have shown that different histological tumor components of Wilms' tumors also reveal different sensitivities to cytostatic agents and ionizing radiation. The aim of this study is to examine the effect of hyperthermia to Wilms' tumors, generally, and to the different tumor tissues composing nephroblastomas. MATERIAL AND METHOD: The 3H-thymidine labelling indices (LI) of 23 Wilms' tumors and one renal rhabdomyosarcoma were studied by an autoradiographic in vitro method at temperatures of 37.5 degrees C/120 min and 42.5 degrees C/120 min. The LI of each tumor was measured and likewise the LI of all histological tumor components defining standard risk and high risk. The effect of hyperthermia was calculated as the percentage of inhibition of 3H-thymidine incorporation. RESULTS: Labelling indices between 22.4% and 46.3% (mean 33.2%) characterized Wilms' tumors as highly malignant and fast growing tumors. The LI of Wilms' tumors of standard risk and high risk did not differ significantly (33.8% vs. 30.4%). Also, epithelium and blastema of the same groups showed comparable high LI of 31.4% and 34.4%, respectively, and of 32.1% and 26.8%, respectively. The LI of stroma was significantly lower (11.9% and 10.9%). The mean LI of fetal-like rhabdomyoblastic cell elements of ten tumors was 24.5%. These tumor cells revealed a significantly higher LI than rhabdomyosarcomatous cells in one Wilms' tumor and one renal rhabdomyosarcoma (10.2% and 9.0%, respectively). The LI of anaplastic structures of one tumor was more than twice as high as the LI of surrounding tumor tissue. In vitro hyperthermia significantly inhibited 3H-thymidine incorporation into all nephroblastomas. Inhibition ranged between 13.7% and 84.6%, at an average of 47.3%. Four high risk tumors, as well as the single anaplastic and rhabdomyosarcomatous cells responded significantly stronger to heat than standard risk tumors (mean inhibition of 62.6% vs. 42.1%). Hyperthermia was more effective for blastema compared to epithelium and stroma. There was no correlation between the effect of hyperthermia and the amount of the 3H-thymidine LI at normothermia. CONCLUSION: The tremendous inhibition of DNA synthesis by hyperthermia particularly in high risk tumors and highly malignant tumor components is of clinical interest for children with Wilms' tumors resistant to conventional therapy.

Wilms' tumor 1 splice variants have opposite effects on the tumorigenicity of adenovirus-transformed baby-rat kidney cells.

The Wilms' Tumor 1 gene (WT1) encodes a transcription factor of the zinc-finger family. As a result of alternative RNA splicing, the gene can be expressed as four polypeptides which differ in the presence or absence of two stretches of amino acids: one of 17 residues (17aa) just N-terminal of the four zinc-fingers and of three residues (K-T-S) between zinc finger 3 and 4. In this study, four human cDNA constructs encoding the Wilms' tumor 1 splice variants were stably transfected into adenovirus-transformed baby rat kidney (Ad-BRK) cells. The in vivo produced WT1 proteins that lacked the KTS residues were found to bind efficiently to both the Egr-1 consensus sequence and the recently described WTE DNA sequence, as determined by electrophoretic mobility shift assays. Our studies show distinct effects of the different WT1 isoforms. Expression of the WT1 (-/+) protein, lacking the 17aa insert, strongly suppressed the tumorigenic phenotype of the Ad-BRK cells. Intriguingly, expression of the WT1 (-/-) protein, lacking both inserts, increased the tumor growth rate. In contrast to the growth in vivo, the growth rate of the transfectants in tissue culture is not influenced by any of the WT1 isoforms. However, the suppression of tumorigenicity appears to be correlated with a reduced ability of the cells to grow in serum-free medium.

Tumors produced in rats with a single dosage of 1,2-dimethylhydrazine.

To evaluate possible nephroblastoma induction in young Sprague-Dawley male rats by 1,2-dimethylhydrazine (DMH), agents including inhibitors and stimulators of the carcinogenesis were tested concurrently in 2 experiments. In series A, rats, 27 days of age, were fed the following as supplements in a basal diet at the final wt% given: hydralazine (0.035%), disulfiram (250 ppm), ferrous sulfate heptahydrate (0.55%; 0.11 g% Fe), isotretinoin (240 ppm), dehydroepiandrosterone (0.30%) in addition to selenium (2 ppm; drinker). At day 15, DMH was injected s.c. at 108 mg base/kg; duration on the diets: 51 weeks. Series B comprised 33 day-old males which were partially hepatectomized (control and indomethacin at 10 mg/l by drinker) or bilaterally gonadectomized for comparison vs sham-operated, and intact groups on s.c. injection of estradiol benzoate (15 micrograms/kg), progesterone (30 mg/kg) and diallyl sulfide (100 mg/kg), the respective controls receiving the peanut oil vehicle. Treatments were begun 8 days post-operative and 17 days later, the single dosage of DMH as in the above was injected. The oil solutions were administered at the specified weekly levels for a total of 52 injections, 2 doses being introduced per week for the 1st 3 weeks. Colon adenocarcinomas comprised the main tumors and occurred in about 15-50% of the rats with total frequencies in the respective control ranges except for decrements with the disulfiram- and iron-fed groups. Renal changes were more involved with series B and nephroblastomas of the left kidney occurred in one animal each of the estradiol benzoate- and diallyl sulfide-injected groups. Of interest, bilateral nephroblastomas were present in one of the saline-injected controls which was gonadectomized. Under the conditions explored, concurrent treatment with DMH inhibitors or synergists had a minimal effect on nephroblastoma induction.

Morphology and growth characteristics of epithelial cells from classic Wilms' tumors.

The ability to establish cell cultures representing the epithelial component of Wilms' tumor was determined for 18 cases of classic Wilms' tumors. From these 18 cases only two resulted in the culture of epithelial cells. Although the tumors from both cases were composed of a prominent epithelial component, other classic tumors not producing epithelial cell cultures also possessed appreciable epithelial components. Likewise, heterotransplants of these two primary tumors failed to give rise to epithelial cell cultures, although cultures of the blastemal element were produced. This suggests that Wilms' tumors may be prone to differentiate in different directions at varying times during tumor growth, possibly dependent on local tumor environment. Epithelial cells from these two classic cases were grown in culture in basal medium composed of a 1:1 mixture of Dulbecco's modified Eagle's medium and Ham's F-12 medium, supplemented with selenium, insulin, transferrin, hydrocortisone, tri-iodothyronine, and epidermal growth factor, on a collagen type I matrix with absorbed fetal calf serum proteins. One of the two cases also required the addition of bovine pituitary extract, ethanolamine, prostaglandin E1, and putrescine for optimum growth. Morphological analysis disclosed that the cultured cells were very similar to normal renal tubular cells in culture, except that the cells displayed little evidence for differentiated active ion transport and tended to grow in a multilayered arrangement. The culture of the epithelial cells from classic Wilms' tumors provides a model system for the study of tumor differentiation and progression.

The use of magnetic resonance imaging in diagnosing Wilms' tumor mimicking a lumbosacral strain and sprain.

Wilms' tumor is the most common tumor of the kidney in childhood. This article discusses the case of a young adult with a Wilms' tumor whose initial presentation appeared similar to a lumbosacral strain. The use of magnetic resonance imaging in diagnosing Wilms' tumor is discussed, along with the common clinical picture of the disease.

Uterine mullerian adenosarcoma following adenomyoma in a woman on tamoxifen therapy.

The clinical and pathologic findings in a 53-year-old woman who developed a uterine adenosarcoma following an adenomyoma are described. During the interval between the diagnosis of adenomyoma and the subsequent diagnosis of adenosarcoma, the patient developed breast carcinoma and received adjuvant chemotherapy that included tamoxifen. The possible stimulatory effects of this drug upon the patient's pre-existing adenomyoma are discussed in view of reports of tamoxifen-associated endometrial carcinoma and uterine sarcomas developing in the setting of estrogen excess.

Inhibitory effect of dietary p-methoxybenzeneselenol on azoxymethane-induced colon and kidney carcinogenesis in female F344 rats.

The effect of dietary p-methoxybenzeneselenol on colon carcinogenesis induced by azoxymethane [(AOM) CAS: 25843-45-2] was studied in female F344 rats. Starting at 5 weeks of age, animals were fed the high-fat diet (control diet) or high-fat diet to which 50 ppm of p-methoxybenzeneselenol (experimental diet) had been added. At 7 weeks of age, all animals except the vehicle-treated controls were administered sc injections of AOM (15 mg/kg body wt, once weekly for 3 wk). Animals were fed the control and experimental diets until 1 week after carcinogen treatment when those animals receiving the p-methoxybenzeneselenol diet were fed the control diet until termination of the experiment. p-Methoxybenzeneselenol in the diet significantly inhibited the incidence (percentage of animals with tumors) of tumors in the colon and kidney, as well as the colon tumor multiplicity (adenomas and adenocarcinomas per animal).