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V Reuter

Publications and source records attributed to V Reuter.

At least 37 records · Page 2Linked to original sources
PubMed1995

Chromosomal abnormalities in choriocarcinomas of the female.

We have studied six cases of choriocarcinomas in the female by conventional cytogenetic analysis and by in situ hybridization using a 12p painting probe, and found evidence for chromosome 12 abnormalities in two of them. Abnormalities of chromosome 12 are a common occurrence in genitourinary tumors of the female, but their significance is not known. We discuss the present findings in relation to those in malignant ovarian germ cell tumors (MOGCTs).

Choriocarcinoma↗
PubMed1995

TAG-72 expression in primary, metastatic and hormonally treated prostate cancer as defined by monoclonal antibody CC49.

Monoclonal antibodies CC49 and B72.3, which recognize a tumor associated glycoprotein (TAG-72) related to sialyted Tn antigen, have been used in clinical trials for radionuclide imaging, and treatment of colon, breast and ovarian carcinoma. In addition, studies with CC49 in patients with metastatic hormone refractory prostate cancer have been initiated based on the observed expression of TAG-72 in primary prostate cancer. We examined whether TAG-72 expression is a common feature of primary, metastatic and hormonally treated prostatic carcinoma. Immunohistochemical analysis of 25 primary prostatic carcinomas confirmed previous data that 21 of 25 specimens (80%) were immunoreactive with CC49. CC49 staining was noted in all 6 well (Gleason score 2 to 4), 8 of 10 moderately (Gleason score 5 to 6) and 7 of 9 poorly (Gleason score 7 to 9) differentiated tumors. CC49 immunoreactivity was noted in 10 of 20 hormonally treated prostate cancers and in 21 of 25 tumors without hormonal therapy. Intense CC49 staining of prostatic intraepithelial neoplasia was present in all 5 specimens examined. In contrast to the primary lesion, many metastatic prostate cancers lacked detectable CC49 immunoreactivity. Of 24 pelvic lymph node metastases from different patients only 4 (17%) had significant CC49 staining and 5 others had rare CC49 positive cells. However, 6 of 12 bone metastases showed CC49 immune staining. One specimen from an anaplastic locally recurrent tumor showed no reactivity. To our knowledge we present the first analysis of TAG-72 expression in a large series of patients with hormonally treated and metastatic prostate cancer, the most likely candidates for CC49 immunotherapy. Our findings that lymph node and bone metastases from prostate cancer are less likely to express significant amounts of TAG-72 than primary prostate cancer suggest that pretreatment biopsy typing for TAG-72 may be necessary to optimize the results of ongoing CC49 imaging and therapy studies.

Adenocarcinoma↗
PubMed1995

Changing pattern of expression of the epidermal growth factor receptor and transforming growth factor alpha in the progression of prostatic neoplasms.

The autocrine/paracrine interaction of the epidermal growth factor receptor (EGFr) and transforming growth factor alpha (TGF-alpha) has been implicated in prostate cancer cell growth and proliferation. To evaluate the role of EGFr and TGF-alpha in prostate cancer progression, we studied the immunohistochemical staining pattern of EGFr and TGF-alpha in malignant primary and hormone-independent metastatic prostate lesions. The specimens evaluated included 37 primary carcinomas (34 hormone-naive and 3 hormone-refractory tumors) and 22 metastases. For each specimen, the pattern of expression was evaluated and staining reactivities graded from 0-3, with 0 representing no staining and 3 representing homogeneous and intense staining. Primary malignant prostate epithelial cells in areas with discrete gland formation showed strong EGFr immunostaining, while stromal cells were generally nonreactive. In untreated primary tumors, TGF-alpha expression was primarily in the stroma, while epithelial cells were weakly positive in several cases. Malignant epithelial cells adjacent to neural elements that stained positive for TGF-alpha was frequently observed. A homogeneous staining pattern for EGFr was noted in 17 (89%) of 19 evaluable androgen-independent-refractory metastases, while TGF-alpha expression was found in 14 (78%) of 18 evaluable cases. Overall, 14 of 18 androgen-independent metastases coexpressed the receptor and the ligand. These results suggest that, unlike primary prostate tumors where a paracrine relationship between EGFr and TGF-alpha appears to predominate, the potential for autocrine stimulation may exist in the majority of metastatic androgen-independent tumors. Furthermore, the changing pattern of expression as the disease evolves from the localized hormone-naive to metastatic androgen-independent condition suggests that strategies aimed at blocking this growth factor pathway may be of therapeutic importance for androgen-independent disease.

Adrenal Gland Neoplasms↗
PubMed1994

P-glycoprotein expression in primary and metastatic transitional cell carcinoma of the bladder.

BACKGROUND: To determine the expression of P-glycoprotein in pre- and post-chemotherapy tumor tissue samples from patients with transitional cell carcinomas treated with M-VAC (methotrexate, vinblastine, adriamycin and cisplatin). PATIENTS AND METHODS: Fresh frozen tissue sections of primary and metastatic urothelial tumors were stained with mouse monoclonal antibody HYB-241 which recognized an external epitope of P-glycoprotein, using an avidin-biotin immunohistochemical technique. Immunoreactivity was scored separately in tumor cells and endothelial cells. RESULTS: Untreated primary lesions showed immunostaining in 6 of 46 cases (13%), while 6 of 16 (38%) post-therapy primary tumors were immunoreactive. None of the untreated metastases (0 of 17) were positive, however, 6 of 11 (55%) post-therapy specimens showed varied percentages of positivity for p-glycoprotein (p = 0.002). The highest percentage, 50%-70% of tumor cells stained, was observed in metastatic lesions from patients who had received 6 or more chemotherapy cycles. No difference in the proportion of endothelial cells stained was observed in pre- and post-therapy specimens. However, 3 of 6 post-therapy samples obtained from 5 individual patients showed MDR1 up-regulation on endothelial cells. CONCLUSIONS: The data show that an increase in the proportion of cells expressing P-glycoprotein occurs after exposure to a combination chemotherapy program containing drugs known to select for P-glycoprotein expression in vitro. The observation of increased immunoreactive endothelial cells suggests transactivation of the MDR1 in these cells. While data are preliminary, P-glycoprotein expression in capillary endothelial cells may contribute to drug resistance. Taken together, these mechanisms may contribute to therapeutic failure in patients with bladder tumors treated with chemotherapy.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Allelic loss and somatic differentiation in human male germ cell tumors.

The complex but poorly understood human male germ cell tumors offer unusual opportunities for the genetic analysis of malignant transformation and embryonal differentiation in a pluripotential stem cell lineage. Histologically, these tumors are divided into two major subgroups, seminomas which are characterized by inability to express embryonal differentiation, and non-seminomas which are characterized by ability to express embryonal as well as extra-embryonal patterns of differentiation. To understand the role of genetic factors in the development of these tumors and the regulation of differentiation expressed by them, we carried out a detailed allelotype analysis by the loss of heterozygosity assay. This analysis revealed frequent deletions in known tumor suppressor genes (RB1, DCC, NME), a number of previously described sites of candidate tumor suppressor genes (3p, 9p, 9q, 10q, 11p, 11q and 17p), as well as several novel sites (2p, 3q, 5p, 12q, 18p and 20p). Our results also showed that well differentiated teratomas exhibit a significantly higher level of allelic loss compared to the less differentiated embryonal carcinomas. In addition, certain loci and genes exhibited frequent non-random deletion in teratomas (D3S32, D3S42, D5S12, D10S25, D11S12, RB1, TP53, NME1, NME2, D17S4, D18S6 and D20S6) and embryonal carcinomas (IFNB, D9S27). Among these loci, the NME genes were notable for a high degree of genetic loss (> 70%) in teratomas. These results suggested that nonrandom loss or inactivation of certain genes may be associated with tumor development and loss or inactivation of other genes may be associated with somatic differentiation.

Alleles↗
PubMed1993

Genetic alterations in bladder cancer.

To see whether genetic alterations follow a sequence of events leading to bladder cancer progression, 60 paired bladder tumours and normal tissues were analysed with polymorphic DNA markers, correlating loss of heterozygosity (LOH) at candidate tumour suppressor gene sites with pathological indices of poor clinical outcome. Distinct genotypic patterns were associated with early and late stages of bladder cancer. 9q deletions were observed in all superficial papillary tumours (Ta) and almost all tumours invading the lamina propria (T1), suggesting that this event associates with the development of superficial bladder tumours. However, 3p, 5q, and 17p deletions were absent in the Ta tumours but were identified in invasive bladder cancers. Two genetic pathways characterise the evolution of superficial bladder tumours. 9qLOH was detected in most Ta tumours, but in only 43% of muscle invasive neoplasms. Our hypothesis is that certain chromosomal abnormalities have a defined role in bladder tumour development, whereas others correlate with pathological indices of poor clinical outcome.

Alleles↗
PubMed1993

The role of neoadjuvant hormonal manipulation in localized prostatic cancer.

BACKGROUND: Although hormonal manipulation is standard therapy for patients with metastatic prostatic cancer, its use in localized disease in combination with surgical extirpation of the gland has not been investigated thoroughly and systematically. METHODS: The authors report their initial pilot studies using preoperative neoadjuvant endocrine therapy. RESULTS: Although marked reduction in serum prostate-specific antigen (PSA) levels occurred in all patients, the PSA level after endocrine manipulation did not predict the pathologic stage. In addition, immunohistochemical staining of the radical prostatectomy specimen for PSA, in several patients with a zero serum PSA level, after endocrine therapy revealed intense PSA staining in the cancer cells but not in benign epithelium. The effects on tumor downstaging were inconclusive. Overall, only 33% of patients had organ-confined disease, but in some patients, complete tumor regression (PO) occurred. CONCLUSIONS: Neoadjuvant hormonal therapy in prostatic cancer, although definitely not standard therapy, bears investigation. In addition to the effect on the "index" cancer, it also provides an opportunity to evaluate the effect of hormonal agents on microfocal ("early") cancer and known precursors of malignant change. Therefore, it may provide a means of assessing agents of potential use in the development of chemopreventive strategies.

Administration, Oral↗
PubMed1993

Adult prostatic sarcoma.

A 57-year-old male with a high grade leiomyosarcoma of the prostate is presented. The local extent of the tumor was accurately described by magnetic resonance imaging (MRI). Following chemotherapy, the tumor volume was reduced by 60% and was judged to be clinically resectable by MRI. Despite radical cystoprostatectomy, the patient died of metastatic disease.

Humans↗
PubMed1993

Untreated hypernephroma of thirty-three years.

The literature cites long-term (> 10 years) survivals after surgical treatment for renal cell carcinoma compared with few untreated cases with similar survival. We report the longest survival between time of diagnosis and documented distant metastases from an untreated renal cell cancer.

Aged↗
PubMed1993

Intracardiac teratoma 15 years after treatment of a nonseminomatous germ cell tumor.

A patient presented to our center with a 15-year history of medical, surgical and radiation treatment for a nonseminomatous germ cell tumor and contralateral seminoma. He experienced a cerebral infarction, which led to the diagnosis of an intracardiac tumor. The tumor was resected and found to be a mature teratoma. We discuss the diagnosis and management of this unusual metastatic nonseminomatous germ cell cancer.

Adult↗
PubMed1993

Use of neoadjuvant androgen deprivation therapy in clinically localized prostate cancer.

Radical prostatectomy is an excellent form of treatment of pathologically organ-confined prostatic carcinoma. However, most clinically localized prostatic cancers have pathologic evidence of extracapsular spread, limiting the effectiveness of radical surgery in curing this disease. To improve the organ-confined rate of prostate cancer, we studied the effect of preoperative or neoadjuvant androgen deprivation therapy (ADT). Our initial attempts focused on downstaging locally advanced tumors (T3) with neoadjuvant diethylstilbestrol (3 mg/d). Our study of 59 patients revealed that although there were significant clinical signs of downstaging, most patients still had extraprostatic disease. However, a subset of patients demonstrated marked pathologic regression, so we initiated a nonrandomized but controlled study of neoadjuvant ADT (goserelin acetate and flutamide for 3 months) followed by radical prostatectomy in patients with clinically localized prostate cancer. Of 72 control and 69 study patients, the rate of organ-confined disease was 48% and 74% (including 4% with no detectable residual carcinoma), respectively. In addition, the margin-positive rate was 33% and 10%, respectively. As demonstrated in the previous study, changes in serum prostate-specific antigen, transrectal ultrasonographic evaluations, and digital rectal examinations could not predict those patients with favourable pathology. Our results suggest that neoadjuvant ADT may improve the pathologic stage in some prostatic carcinomas and is worthy of further investigation in the efforts to augment the effectiveness of radical prostatectomy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Allelic deletions in the long arm of chromosome 12 identify sites of candidate tumor suppressor genes in male germ cell tumors.

Human male germ cell tumors (GCTs) result from malignant transformation of premeiotic or early meiotic germ cells and exhibit embryonal-like differentiation of the three germinal layers. The genetic basis of origin and expression of differentiated phenotypes by GCTs are poorly understood. Our recent cytogenetic analysis of a large series of GCTs has shown that two chromosome 12 abnormalities, an isochromosome for the short arm [i(12p)] and deletions in the long arm [del(12q)], characterize these tumors, which led us to suggest that the deletions represent loss of one or more candidate tumor suppressor genes whose products regulate the normal proliferation of the spermatogonial stem cells. We undertook a molecular mapping of the deletions by comparing germ-line and tumor genotypes of eight polymorphic loci in paired normal/tumor DNA samples from 45 GCT patients. Analysis of loss of constitutional heterozygosity at these loci revealed two regions of frequent loss (> 40%), one at 12q13 and the other at 12q22, identifying the sites of the postulated tumor suppressor genes. One tumor (no. 143A) exhibited a homozygous deletion of a region of 12q22, which included the MGF gene. The KIT and MGF genes have been shown to play key roles in embryonal and postnatal development of germ cells; therefore, we evaluated their expression by Northern blot analysis in a panel of three GCT cell lines and 24 fresh GCT biopsies. Deregulated expression of MGF and KIT, which was discordant between seminomatous and nonseminomatous lesions, was observed.

Alleles↗
PubMed1992

Surgical resection of solitary metastases after chemotherapy in patients with nonseminomatous germ cell tumors and elevated serum tumor markers.

BACKGROUND: Chemorefractory metastatic germ cell tumors and elevated tumor markers generally indicate inoperable disease. METHODS: Solitary metastases were resected in 15 patients who had a nonseminomatous germ cell tumor and an elevated alpha-fetoprotein (AFP) and/or human chorionic gonadotropin (HCG) serum level after treatment with cisplatin-based chemotherapy. Patients underwent resection for a residual mass after chemotherapy or for a new solitary metastasis after achieving a complete response (CR) to salvage chemotherapy. RESULTS: Seven patients were disease-free after surgical resection alone. All five patients with an elevated HCG level had a relapse after surgery compared with 3 of 10 patients with only an elevated AFP level. Only 4 of 10 patients with a retroperitoneal metastasis had a relapse after surgery compared with 4 of 5 patients with visceral disease. Eleven of 15 patients overall were disease-free after surgery and subsequent chemotherapy after a relapse. CONCLUSIONS: Surgical resection of a solitary metastasis despite elevated serum tumor markers should be considered in patients who have not had a durable CR to cisplatin-based chemotherapy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1992

Phase II trial of suramin in patients with advanced renal cell carcinoma: treatment results, pharmacokinetics, and tumor growth factor expression.

Twenty-six patients with advanced renal cell carcinoma were treated with suramin administered by continuous infusion, with dosing determined by a nomogram. One patient achieved a partial response and five patients achieved a minor response or had stable disease for > 3 months. Toxicities included an immune-mediated thrombocytopenia in one patient and Staphylococcus sepsis that was not associated with neutropenia in five patients. Pharmacokinetic parameters were determined by the ADAPT II MAP-Bayesian parameter estimation program. Patient data were fit using a two-compartment open model and first-order rate elimination. This showed a wide interpatient variation in time to target level (median, 13.8 days), volume of distribution (median, 15.2 liters/m2), and t1/2-beta (median, 20.6 days). The patients who achieved a partial response, minor response, or stable disease had a slower elimination rate of suramin, compared to patients with progressive disease. Tumor specimens were obtained prior to therapy and were analyzed for the production of five different growth factor-specific RNA transcripts. These included transforming growth factor alpha, acidic fibroblast growth factor, basic fibroblast growth factor, and platelet-derived growth factor types A and B. No difference in the pattern of growth factor expression was seen in tumors of responding and nonresponding patients. Suramin does not have significant antitumor activity in renal cell carcinoma. The wide variability in pharmacokinetics suggests that individual dosing should be used in future trials of suramin for treatment for other malignancies. Pertinent corollary studies of tumor biology and clinical pharmacology should be included whenever possible in clinical trials in patients with renal cell carcinoma.

Adult↗
PubMed1992

Cytogenetic analysis of 124 prospectively ascertained male germ cell tumors.

We report the cytogenetic analysis of 124 adult male germ cell tumors ascertained consecutively at the Memorial Sloan-Kettering Cancer Center between 1988 and 1990. Biopsies from testicular and extragonadal primary and metastatic lesions studied included all histological subtypes of germ cell tumors and cases of malignant transformation. Nonrandom numerical and structural chromosomal abnormalities including i(12p), the previously described characteristic marker of these tumors, were determined, and their frequency was compared between histological subtypes, between gonadal and extragonadal lesions, and between primary and transformed lesions. The frequency and copy number of i(12p) were found to be higher in nonseminomas compared with seminomas. Nonrandom sites of chromosome rearrangements associated with specific histologies comprised 1p32-36 and 7q11.2 in teratomas and 1p22 in yolk sac tumors. Some tumors that underwent malignant differentiation exhibited chromosome changes previously described to be nonrandomly associated with de novo tumors with the same histological characteristics. Cytological evidence of gene amplification in the form of homogeneously staining regions and/or double minutes was detected in 24% of extragonadal lesions, mainly metastatic tumors, suggesting amplification of a gene(s) associated with metastatic progression of these tumors. While a number of previous small cytogenetic series or individual case reports of germ cell tumors identified several of the features of these tumors reported here, this series comprises analysis of the largest group of tumors ascertained consecutively at a single institution, defines the incidence of nonrandom abnormalities in tumor subsets, and addresses their biological significance.

Cell Transformation, Neoplastic↗