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Biomedical subjects

A Rademaker

Publications and source records attributed to A Rademaker.

At least 37 records · Page 2Linked to original sources
PubMed1998

Medical contraindications are not a major factor in the underutilization of breast conserving therapy.

BACKGROUND: Multiple randomized trials have demonstrated that survival after breast conserving therapy (BCT) is equal to survival after mastectomy, but large population-based studies indicate that > 50% of patients with early stage breast cancer continue to undergo mastectomy. This study was undertaken to determine whether medical contraindications to BCT or patient choice are responsible for high mastectomy rates. STUDY DESIGN: Four hundred thirty-two patients with stage 0, I, or II breast carcinoma were prospectively evaluated by a multidisciplinary team for eligibility for BCT. Standard criteria developed by a joint committee of the American College of Surgeons, American College of Radiologists, College of American Pathologists, and Society of Surgical Oncology were used. Eligible patients were offered a choice among BCT, mastectomy, or mastectomy and immediate reconstruction. RESULTS: Only 97 of the 432 patients had contraindications to BCT. The incidence of contraindications varied by stage: 10% for stage I, 28% for stage II, and 33% for stage 0 (p < 0.01). The type of contraindications also varied with stage. Age, histologic tumor type, and axillary node status (when controlled for tumor size) did not influence rates of BCT. Of eligible patients, 81% chose BCT, independent of age or race. CONCLUSIONS: Medical contraindications to BCT are not major factors resulting in high mastectomy rates. Strategies like neoadjuvant chemotherapy, which addresses medical contraindications, are unlikely to have a major impact on national rates of BCT.

Adult↗
PubMed1998

Abnormalities for chromosomes 13 and 21 detected in spermatozoa from infertile men.

Sperm samples from infertile men with oligozoospermia or teratozoospermia were studied by multicolour fluorescence in-situ hybridization (FISH) using DNA probes for chromosomes 13 and 21. A total of 90 809 sperm nuclei from nine infertile men and 182 799 sperm nuclei from 18 control donors were analysed. There was a highly significant increase in the frequency of spermatozoa disomic for chromosome 13 in infertile patients (0.28%) compared to control donors (0.13%) (two-tailed Z statistic P < 0.0001) and for chromosome 21 (0.48% in infertile men versus 0.37% in controls, P < 0.0001). Also there was a significantly increased frequency of diploid spermatozoa in infertile men (0.85%) compared to control donors (0.66%) (P < 0.0001). Our previous studies on these same infertile patients demonstrated increased frequencies of sperm disomy for chromosomes 1 and XY. This suggests that infertile men, who are prime candidates for intracytoplasmic sperm injection, may be at a very small increased risk of aneuploid offspring.

Adult↗
PubMed1998

Donor age and the frequency of disomy for chromosomes 1, 13, 21 and structural abnormalities in human spermatozoa using multicolour fluorescence in-situ hybridization.

The purpose of this study was to determine if a donor age effect exists for the frequency of aneuploidy and other chromosome abnormalities in human spermatozoa. Sperm samples were collected from 18 healthy men from the general population. Each individual belonged to one of six age groups (20-24, 25-29, 30-34, 35-39, 40-44, > or = 45 years) with three men in each group. Two multicolour fluorescence in-situ hybridizations were performed on spermatozoa from each donor using probes for chromosomes 13 and 21, and two chromosome 1-specific probes allowed for detection of duplications and deletions as well as disomy of chromosome 1. The abnormality frequencies and the Pearson correlation coefficients were calculated to determine if a relationship existed between donor age and the frequency of chromosome abnormalities in spermatozoa. A statistically significant association with donor age was detected for the frequency of acentric fragments of chromosome 1 (P < 0.05).

Adult↗
PubMed1998

Exogenous epidermal growth factor exerts promoting action during the early phase of rat urinary bladder carcinogenesis.

Using the heterotopically transplanted rat urinary bladder (HTB) model that was developed in our laboratory, we examined the relationship between the duration of epidermal growth factor (EGF) treatment and acquisition of EGF-independence of urinary bladder tumors that were induced by EGF stimulation. After treatment with N-methyl-N-nitrosourea (MNU) (0.25 mg/0.5 ml of 0.9% NaCl once a week for 3 consecutive weeks), animals at week 3 received EGF [250 ng/0.5 ml phosphate-buffered saline (PBS)] into the HTBs once a week for 20, 28, or 36 weeks. For examination of the effect of EGF withdrawal, one half of the rats received the vehicle (PBS) only beginning at week 23 or week 31 for 8 weeks. When animals were examined at week 23, the incidence and the mean number of tumors per bladder were low, irrespective of EGF treatment. In the bladders that had been exposed to EGF during the first 20 weeks after MNU administration, however, both the incidence and the mean number of tumors per bladder had increased significantly at week 31, regardless of whether or not EGF treatment was continued beyond week 23. Between weeks 31 and 39, EGF treatment demonstrated no effect; both the incidence of tumors and the mean number of tumors were the same as those at week 31. These results suggest that EGF exerts its promoting effect only during the early phase of MNU-initiated bladder carcinogenesis, but that its effect becomes manifest during the subsequent 8 weeks. EGF independence may be due to establishment of an autocrine growth-stimulatory mechanism in bladder tumors.

Animals↗
PubMed1998

The usefulness of touch preparation cytological evaluation and prostatic capsule involvement in prediction of prostate cancer recurrence.

PURPOSE: Touch preparation cytology has been used in oncology as a technique to assist in predicting local tumor recurrence. We prospectively investigated the relationship between this cytological evaluation and the standard histological method of assessing specimens, measuring the distance from the tumor to the various anatomical boundaries and disease recurrence in radical retropubic prostatectomy patients. MATERIALS AND METHODS: In a prospective study of 91 consecutive clinical stages T1c and T2 cancer cases radical retropubic prostatectomy touch preparation cytology was performed intraoperatively in an anatomical fashion (apex, posterior, lateral right and left, and base). A single blinded cytopathologist reviewed all prostate touch preparation specimens and categorized them as malignant, benign or atypical cells. Benign or atypical cells were classified as negative cytology. Detailed histological margin analysis of the surgical specimens was also done in which distances between the tumor front, and prostate capsule (inner and outer edge) and surgical margins (apex, posterior, right and left lateral, and base) were measured. All specimens were re-staged by the same pathologist. Median followup was 38 months. Disease recurrence was determined biochemically (prostate specific antigen), and with bone scans, prostatic fossa biopsies and digital rectal examinations. RESULTS: Of the 91 specimens 25 were excluded from study because distance measurements could not be made for technical reasons. Multivariate analysis was performed on the remaining 66 patients based on the variables of stage, age, cytology status, distance from tumor to the inner prostatic capsule, distance from tumor to the surgical margin and postoperative Gleason sum. The only variable with independent prognostic value was postoperative Gleason sum (p = 0.04). Cytology status was not statistically significant (p = 0.07) nor were distance data to the inner capsule (p >0.05) and surgical margin (p >0.05). CONCLUSIONS: Although touch preparation cytology does not enhance prognostic information already provided by Gleason sum, it does correlate highly with postoperative Gleason sum. Other gross macroscopic variables, that is pathological stage, margin status and distance measurements, although lacking in independent predictive value, correlated with postoperative Gleason sum. The constancy of Gleason sum leads us to believe that the key to predicting prostatic cancer behavior lies not on the macroscopic but on the molecular or cellular level. Of the various factors analyzed in this study postoperative Gleason sum remains the most powerful predictor of recurrence risk.

Aged↗
PubMed1997

Phase II study of induction and adjuvant chemotherapy for squamous cell carcinoma of the head and neck. A long-term analysis for the Illinois Cancer Center.

BACKGROUND: In 1982, the Illinois Cancer Center initiated a Phase II trial in which the following treatment was administered: Induction chemotherapy (cisplatin and infusional 5-fluorouracil [5-FU]) was administered before definitive local therapy. Definitive local therapy, consisting of surgery, radiation, or both, was followed by three cycles of the same chemotherapy program. METHODS: Eligible patients had Stage III or IV squamous cell carcinoma of the head and neck with no distant metastases. Three cycles of induction chemotherapy were given. Cisplatin, 100 mg/m2, was infused over 60 minutes on Day 1; thereafter, 5-FU (1000 mg/m2/day) was given continuously for 5 days. Cycles were repeated at 3-week intervals. Local therapy was individualized, according to tumor stage and site. Patients who responded were to receive an additional three cycles of chemotherapy after surgery or radiation. RESULTS: Eighty-one patients were entered into the trial, and 71 were considered both eligible and evaluable. After induction chemotherapy, 59 patients (83%) responded, 23 of whom experienced complete response. Sixty-nine patients completed definitive local treatment, but only 22 proceeded to the planned adjuvant cycles of treatment. Median follow-up of surviving patients was 12 years. At last follow-up, 13 patients were alive and free of malignancy, 9 of whom never had disease recurrence or a second primary tumor. These 13 patients had an acceptable quality of life, were ambulating, and were fully capable of caring for themselves. Overall, nine patients had second primary malignancies. Thirty-four percent of patients were alive at 5 years, and 21% were alive at 10 years. Of 58 deaths, 44 resulted from progressive disease and 8 resulted from second primary cancers. Four patients died of unrelated causes, and two suffered lethal acute toxicity from the chemotherapy program. Late toxicity was moderate. Among 23 patients surviving at least 6 years, there were 3 cases of hypothyroidism, presumed to be secondary to radiation. Xerostomia was modest, consistent with usual radiation effects. Of the 13 patients who were alive and free of malignancy at last follow-up, none had clinical manifestations of serious late end organ toxicity. CONCLUSIONS: During long term follow-up after multimodal treatment of locally advanced squamous cell carcinoma, no obvious benefit was observed from the chemotherapy component of the treatment regimens rendered. Only 21% of patients achieved 10-year survival with the following causes of failure, in descending order of frequency: disease recurrence, second malignancies, other medical problems, and treatment-related deaths. The results of this trial are consistent with the results of other induction chemotherapy trials, indicating the need for innovative treatment strategies. These data do not support the continued use of induction chemotherapy with the cisplatin and infusional 5-FU program.

Adult↗
PubMed1997

Chromosomal abnormalities in sperm from testicular cancer patients before and after chemotherapy.

Sperm chromosome abnormalities were assessed in testicular cancer patients before and after treatment with BEP (bleomycin, etoposide, cisplatin). The frequencies of disomy for chromosomes 1, 12, X, Y and XY were assessed along with diploid frequencies and sex ratios by multicolour fluorescence in situ hybridization (FISH). For each cancer patient, a minimum of 10,000 sperm was assessed for each chromosome probe before and after chemotherapy (CT). Data was analysed "blindly" by coding the slides. A total of 161097 sperm were analyzed, 80,445 before and 80,642 after treatment. The mean disomy frequencies were 0.11% pre-CT vs 0.06% post-CT for chromosome 1, 0.18% vs 0.15% for chromosome 12, 0.10% vs 0.9% for the X chromosome, 0.13% vs 0.10% for the Y chromosome and 0.25% vs 0.20% for XY sperm. There was no significant difference in the frequency of disomy pre-CT vs post-CT for any chromosome except that chromosome 1 demonstrated a significant decrease after CT. The "sex ratios" and frequency of diploid sperm were also not significantly different in pre and post-CT samples with 50.2% X-bearing sperm pre-CT and 50.5% X post-CT and 0.14% diploid sperm pre-CT vs 0.15% diploid sperm post-CT. There was no significant donor heterogeneity among the cancer patients. None of the values in the cancer patients differed significantly from 10 normal control donors. Thus our study suggests that BEP chemotherapy does not increase the risk of numerical chromosomal abnormalities in human sperm.

Adult↗
PubMed1997

Reliability of estimates of diploid human spermatozoa using multicolour fluorescence in-situ hybridization.

Multicolour fluorescence in-situ hybridization (FISH) analysis permits distinction between disomic and diploid spermatozoa. Thus estimates of the frequency of diploid spermatozoa can be obtained for human semen samples. The issue of the accuracy and reliability of these diploidy estimates has been addressed by analysing diploidy frequencies in 10 men using the same sperm sample to estimate diploidy twice-once during two-colour FISH analysis of disomy for chromosomes 1 and 12 and a second independent analysis of three-colour FISH for disomy estimates for chromosomes X and Y (with chromosome 1 used as the autosomal control). A minimum of 10,000 spermatozoa per hybridization per male was counted for a total of over 200,000 spermatozoa analysed. The mean frequency of diploid spermatozoa was 0.13% for the autosomal study and 0.14% for the sex chromosomal study, which were not significantly different. One donor had extremely divergent values of diploidy in the two studies. Analysis of values in the other nine donors demonstrated no significant difference in the two diploidy estimates. These results indicate that the FISH technique is an accurate and reliable method for determining diploid frequencies in human spermatozoa.

Cell Nucleus↗
PubMed1997

Analysis of human sperm karyotypes in testicular cancer patients before and after chemotherapy.

Sperm karyotype analysis was performed on testicular cancer patients before and after treatment with BEP (bleomycin, etoposide, and cisplatin). A total of 788 sperm chromosome complements was studied, 236 before chemotherapy (CT) and 552 post-CT. There was no significant difference in the total frequency of sperm chromosomal abnormalities pre-CT (10.2%) compared to post-CT (10.7%). Similarly, there were no significant differences in the frequencies of numerical abnormalities (2.5% pre-CT vs. 2.4% post-CT) or structural abnormalities (6.4% pre-CT vs. 7.4% post-CT). The percentage of X-bearing sperm was also not significantly different before (46.3%) and after CT (50.1%). The results in cancer patients were not significantly different from those in control donors. This study corroborates results from our previous analysis of these same men using multicolor fluorescence in situ hybridization for assessment of aneuploidy for chromosomes 1, 12, X, Y, and XY. Together, these two studies suggest that the sperm of men receiving BEP chemotherapy are not at increased risk of chromosomal abnormalities two or more years after treatment.

Adult↗
PubMed1997

Intracellular levels of SGP-2 (Clusterin) correlate with tumor grade in prostate cancer.

Our previous observations in LNCaP cells in vitro demonstrated an association between apoptotic cell death resistance and SGP-2 (Clusterin) overexpression. Accordingly, we hypothesized that high levels of cellular SGP-2 would aid in identifying biologically aggressive prostate cancer cells with unique survival advantages. To test this hypothesis, 40 archival radical prostatectomy and/or biopsy specimens of varying grades of prostate cancer were subjected to immunohistochemical SGP-2 staining. The resulting epithelial stains were quantified subjectively on a scale of 1-3 by four independent observers. Benign prostatic epithelial cells from young donors served as controls and showed a consistently weak staining intensity. In contrast, prostate cancer specimens showed varying degrees of staining intensity that correlated with a Gleason pattern (P = 0.006). This correlation supports the hypothesis that protection from apoptotic death may account, in part, for biologically aggressive tumor behavior.

Adenocarcinoma↗
PubMed1996

Epidermal growth factor-responsive and -refractory carcinomas initiated with N-methyl-N-nitrosourea in rat urinary bladder.

We tested the role of epidermal growth factor (EGF) in the development of low-grade superficial bladder tumors by using a heterotopically transplanted rat urinary bladder system. Weekly EGF administration (250 ng/0.5 ml of phosphate-buffered 2.1% NaCl solution) for 28 weeks into heterotopically transplanted rat urinary bladders initiated with a low dose of N-methyl-N-nitrosourea resulted in a significant increase in the incidence (17 of 25 versus 6 of 30 rats; P < 0.001) and the mean number of tumors per bladder (1.08 versus 0.20; P < 0.001) as compared with those for a vehicle-only group. Changing to vehicle without EGF for the last 8 weeks resulted in tumors in 8 of 24 rats (P = 0.02 versus the EGF group), comparable to the rate for controls. Switching from vehicle to EGF for the last 8 weeks resulted in tumors in 15 of 24 rats, comparable to the rate in the 28-week EGF group. When tumors were divided into two groups according to size (>4.2 mm3 and </= 4.2 mm3), expression of EGF receptor (EGF-R) was found in 24 of 25 "large" tumors as compared with 5 of 17 "small" tumors (P < 0.0001). The results of in situ hybridization for EGF-R correlated well with those of immunohistochemical study. These data suggest the possibility that recurrences of low-grade superficial bladder tumors are related to the continuing presence of EGF in the urine, and that blocking of EGF-R should be evaluated as a tumor inhibitor.

Animals↗
PubMed1996

Preoperative "chemoradiation" for stages II and III rectal carcinoma.

OBJECTIVE: To determine whether preoperative administration of combination chemotherapy and external beam irradiation ("chemoradiation") for patients with stage II or stage III rectal carcinoma had an impact on perioperative morbidity on oncologic outcome, as compared with patients not receiving preoperative chemoradiation. DESIGN: A group of patients with stage II or stage III rectal carcinoma receiving preoperative chemoradiation were followed up prospectively and compared in a nonrandomized fashion with an inception cohort group of similar patients. SETTING: Northwestern Memorial Hospital, Chicago, Ill, a tertiary care academic medical center. PATIENTS: Thirty patients with rectal carcinoma undergoing preoperative chemoradiation were compared with 56 patients not undergoing preoperative chemoradiation, and also with a subset group of 24 patients who received standard postoperative adjuvant chemoradiation. INTERVENTION: External beam radiation, 45 to 50 Gy, was delivered concurrently with fluorouracil and mitomycin 4 to 8 weeks prior to surgical resection. MAIN OUTCOME MEASURES: Patients were followed up at regular intervals for either tumor recurrence or death. In addition, the group receiving preoperative chemoradiation was evaluated for major preoperative morbidity. RESULTS: All patients agreeing to preoperative chemoradiation completed therapy. Perioperative major morbidity in this group (13%) was comparable to previously published results. Of the 56 patients with stage II or stage III rectal carcinoma not receiving preoperative chemoradiation, only 24 (43%) completed standard postoperative adjuvant chemoradiation. Patients receiving preoperative chemoradiation (n = 30), patients not receiving preoperative chemoradiation (n = 56), and the subset of the group not receiving preoperative chemoradiation who completed standard postoperative chemoradiation (n = 24) were followed up for a mean of 39 months, 31 months, and 32 months, respectively. Five-year actuarial local control rates were 96%, 83%, and 88%, respectively. Disease-free-survival rates were 80%, 57%, and 47%, respectively. Overall survival rates were 85%, 48%, and 78%, respectively. CONCLUSIONS: Preoperative chemoradiation in the treatment of stage II or stage III rectal carcinoma is well tolerated and not associated with an increase in subsequent perioperative major morbidity. In addition, local control, disease-free survival, and overall survival compare favorably with a nonrandomized inception cohort group of patients receiving standard postoperative adjuvant chemoradiation.

Adenocarcinoma↗
PubMed1996

Thrombopoietin-stimulated ex vivo expansion of human bone marrow megakaryocytes.

The effect of thrombopoietin (TPO) on megakaryocytopoiesis (MKP) has been mainly studied using clonogenic assays in murine systems. In this study, we evaluated MKP in liquid culture using human bone marrow cells. While interleukin 3 (IL-3) and stem cell factor (SCF) are potent activators of TPO-stimulated MKP in the murine system, only IL-3 exhibited synergistic activity with TPO in cultures of human bone marrow. The IL-3 effect on TPO-stimulated megakaryocyte (MK) proliferation, expressed as the absolute number of MKs per seeded CD34+ cell, was more pronounced with purified CD34+ cell (8 +/- 1.6 SE versus 2.8 +/- 0.7 SE in the presence and absence of IL-3, respectively) than with mononuclear cells (MNC) (16 +/- 2.8 SE versus 11 +/- 2.0 SE). This effect of IL-3 on TPO-stimulated MK proliferation was due to a general proliferation of all cell types since the relative frequency of MKs (32.1 +/- 3 SE and 55.8 +/- 3 SE in MNC and CD34+ cells, respectively) was not affected by IL-3. The effect of TPO alone, TPO + IL-3, TPO + SCF, and TPO + IL-3 + SCF on MK proliferation was examined in MNC and CD34+ cultures. Greater numbers of MK per seeded CD34+ were observed in MNC compared to CD34+ cultures under all conditions except when TPO was added with both IL-3 and SCF. The enhancing effect of MNC was also observed on MK ploidy in the presence of TPO and IL-3. While proliferation and ploidy increase with TPO concentration in the murine system, they are inversely related in the human system. A significant 2.5-fold enhancement of TPO-induced MK proliferation was observed when purified CD34+ cells were cultured in inserts separated from human bone marrow stroma, indicating that soluble stimulatory factors are released from the stroma. These observations will be useful for ex vivo expansion of MKs to treat post-transplant or chemotherapy-associated thrombocytopenia.

Animals↗
PubMed1996

Effect of breast-tissue characteristics on the outcome of clinical breast examination training.

PURPOSE: To compare the effects of clinical breast examination (CBE) training on lump-detection rates in simulated premenopausal and postmenopausal breast tissue. METHOD: Two sets of six silicone models were made with background breast tissue simulating premenopausal tissue (most nodular, least soft) and postmenopausal breast tissue (least nodular, most soft) respectively. Eighteen lumps were located in each set of models. In September 1994, 82 housestaff and attending physicians with outpatient practices in the Division of General Internal Medicine at Northwestern University Medical School were randomized to a CBE-teaching intervention or a control group. Lump-detection rates for the two sets of models were measured before and after the teaching intervention. Analysis of covariance was used to analyze the effect of CBE training on examination sensitivity and specificity, controlling for baseline rates. RESULTS: CBE training increased lump-detection rates similarly and significantly in models simulating premenopausal and postmenopausal tissue, respectively. Specificity declined after training in models simulating postmenopausal tissue (p = 0.02) but was unchanged in models simulating premenopausal tissue (p = 0.54). CBE training had greater influence on sensitivity among house-staff than among attending physicians (p = 0.02). CONCLUSION: CBE training similarly affects lump detection in simulated premenopausal and postmenopausal breast tissue, but adversely affects specificity in simulated postmenopausal tissue only.

Analysis of Variance↗
PubMed1996

Phase I/II study of combined granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor administration for the mobilization of hematopoietic progenitor cells.

PURPOSE: To study the toxicity and efficacy of combined granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) administration for mobilization of hematopoietic progenitor cells (HPCs). MATERIALS AND METHODS: Cohorts of a minimum of five patients each were treated subcutaneously as follows: G-CSF 5 micrograms/kg on days 1 to 12 and GM-CSF at .5, 1, or 5 micrograms/kg on days 7 to 12 (cohorts 1, 2, and 3); GM-CSF 5 micrograms/kg on days 1 to 12 and G-CSF 5 micrograms/kg on days 7 to 12 (cohort 4); and G-CSF and GM-CSF 5 micrograms/kg each on days 1 to 12 (cohort 5). Ten-liter aphereses were performed on days 1 (baseline, pre-CSF), 5, 7, 11, and 13. Colony assays for granulocyte-macrophage colony-forming units (CFU-GM) and erythroid burst-forming units (BFU-E) were performed on each harvest. RESULTS: The principal toxicities were myalgias, bone pain, fever, nausea, and mild thrombocytopenia, but none was dose-limiting. Four days of treatment with either G-CSF or GM-CSF resulted in dramatic and sustained increases in the numbers of CFU-GM per kilogram collected per harvest that represented 35.6 +/- 8.9- and 33.7 +/- 13.0-fold increases over baseline, respectively. This increment was attributable both to increased numbers of mononuclear cells collected per 10-L apheresis and to increased concentrations of progenitors within each collection. The administration of G-CSF to patients already receiving GM-CSF (cohort 4) caused the HPC content to surge to nearly 80-fold the baseline (P = .024); the reverse sequence, ie, the addition of GM-CSF to G-CSF, was less effective. The CFU-GM content of the baseline aphereses correlated with the maximal mobilization achieved (r = .74, P = .001). CONCLUSION: Combined G-CSF and GM-CSF administration effectively and predictably mobilizes HPCs and facilitates apheresis.

Adolescent↗
PubMed1995

Reliability of aneuploidy estimates in human sperm: results of fluorescence in situ hybridization studies using two different scoring criteria.

Aneuploidy estimates for chromosomes 1, 12, X, and Y were obtained in human sperm from five donors using multicolor fluorescence in situ hybridization (FISH) analysis. Disomy frequencies were obtained by scoring a minimum of 10,000 sperm for each chromosome probe per donor. This analysis was replicated for two scoring criteria: one used one half of a signal domain as the minimum distance between two signals to be counted as two and thus disomic; the other set one signal domain as the minimum distance between two signals. A total of 120,870 sperm were assessed using one half of a domain as the criterion, and 113,478 were scored using one domain as the criterion. The percentage of disomy for chromosomes 1, 12, X, Y, and XY was 0.18, 0.16, 0.15, 0.19, and 0.25, respectively, using the one-half-domain criterion, and 0.08, 0.17, 0.07, 0.12, and 0.16, respectively, using the one-domain criterion. The percentage of disomy decreased significantly with use of one domain as the minimum distance for signal separation for all chromosomes except for chromosome number 12. These lower disomy frequencies correlated well with frequencies derived from human sperm karyotypes analyzed in our laboratory. This suggests that the fluorescent signals for chromosomes 1, X, and Y split into more than one domain in decondensed interphase sperm, and that the use of the one-half-domain criterion would lead to an overestimate of aneuploidy frequencies. The factors known to affect aneuploidy estimates derived from FISH studies are discussed, and recommendations for stringent scoring criteria are proposed.

Adult↗
PubMed1995

Intraluminal epidermal growth factor affects growth of N-methyl-N-nitrosourea-initiated rat bladder carcinoma.

To confirm our recent finding that epidermal growth factor (EGF) appeared to contribute to the tumor-enhancing effect demonstrated by normal rat urine, we conducted 2 experiments using our heterotopically transplanted rat urinary bladder model. In experiment 1, after a single dose (0.25 mg) of N-methyl-N-nitrosourea (MNU), we intravesically administered EGF (0.05 ml of 500 ng/ml phosphate-buffered saline) once a week for 30 weeks. Instillation of EGF induced a significantly larger number of tumors than did instillation of the vehicle (P = 0.03). EGF without MNU initiation did not induce tumors. In experiment 2, 2 groups received instillation of killed Escherichia coli (5 x 10(8) cells)/0.5 ml phosphate-buffered saline once a week for 4 weeks to expand the MNU-initiated cell population. Subsequent EGF treatment significantly increased the incidence of tumors (P = 0.01). In the groups which did not receive killed E. coli, EGF treatment induced a significantly higher number of tumors than did vehicle treatment (P < 0.001). All of the tumors were low-grade, superficial transitional cell carcinomas. These observations indicate that EGF acts as a growth-stimulating factor on dormant neoplastic cells and thereby increases the number of tumors.

Animals↗