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At least 919 records · Page 51Linked to original sources
PubMed1994

[Ultra high-dose chemotherapy with peripheral blood stem cell autotransplantation for refractory testicular cancer].

This is a report of 45-year-old man with advanced nonseminomatous germ cell tumor (stage IIIB2: embryonal carcinoma, yolk sac tumor, seminoma), who had relapse after PVB (cisplatin, vinblastine, bleomycin) chemotherapy. Peripheral blood stem cells (PBSCs) were taken by two consecutive apheresis using a CS-3000 blood separator after high-dose chemotherapy of cytarabine and mitoxantrone. In total, 6.4 x 10(5)/kg of granulocytic cells (CFU-GM) was collected. He was treated with ultra high-dose chemotherapy consisting of carboplatin (800 mg/m2), etoposide (1,000 mg/m2) and cyclophosphamide (100 mg/kg) from day 1, followed by peripheral blood stem cell autotransplantation (PBSCT) on day 9. We transfused 2.4 x 10(5)/kg CFU-GM, which was enough number of stem cells for safe PBSCT. No serious side effects or complications were encountered. The patient achieved partial remission for more than two months. However, he died of respiratory dysfunction caused by metastatic lung cancer 5 months later. It was thought that ultra high-dose chemotherapy with PBSCT might be a new therapy for refractory testicular cancer.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Unrelated, HLA-mismatched multiple human umbilical cord blood transfusion in four cases with advanced solid tumors: initial studies.

Four patients with advanced solid tumors were treated by means of high-dose chemotherapy and HLA-mismatched and unrelated multi-cord blood transfusion. Of these patients, three achieved complete remission and one achieved a partial remission. Little or no graft vs. host disease (GVHD) was observed. Partial donor cell engraftment was suggested by 101 to 320 days for two patients by cytogenetic analysis and hemoglobin F levels in the peripheral blood. Recurrent disease was confirmed clinically on day 210 (4-year-old girl with liposarcoma) and on day 90 (11-year-old boy with non-Hodgkin's lymphoma). These results suggest the possibility that HLA-mismatched and unrelated multi-cord blood transfusion may engraft with little or no GVHD and hasten recovery from marrow suppression that is due to chemotherapy. It remains to be determined, however, whether these results document true stem/progenitor cell engraftment or alternatively transient engraftment of more mature cells along with repopulation by autologous cells.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

[The growing teratoma syndrome report of a case].

A 26-year-old man presented with a swelling of the right scrotal content, lumbago and exertional dyspnea. He underwent high inguinal orchiectomy. Histopathological examination of the specimen revealed yolk sac tumor and mature teratoma. Further evaluation revealed mediastinal and retroperitoneal lymph node metastases (stage IIIA). A single course of BEP (bleomysin, etoposide and cisplatin), two courses of chemotherapy consisting of nedaplatin and irinotecan, and three courses of TIP (paclitaxel, ifosfamide and cisplatin) were delivered. The previous abnormally elevated serum biomarkers (AFP, beta-hCG and LDH) returned to normal levels, but the mediastinal and retroperitoneal masses continued to enlarge slowly. The CT-guided biopsy of the mediastinal mass was performed, and histologic study revealed no evidence of malignancy. He underwent excision of the mediastinal masses and retroperitoneal lymph node dissection. Histologic examination of the resected specimens revealed mature teratoma without malignant components. These results were compatible with growing teratoma syndrome. 30 months after the first excision of mediastinal mass, he underwent the second excision of recurrent mediastinal mass in the absence of biomarker elevation. The resected specimens revealed mature teratoma without malignant components. He is alive for 49 months after high inguinal orchiectomy and free of carcinoma.

Adult↗
PubMed1999

Potentially lethal damage repair and its inhibitory effect of caffeine in two yolk sac tumor cell lines with different radiosensitivities.

PURPOSE: In order to investigate the role of potentially lethal damage repair (PLDR) in cellular radiosensitivity, PLDR and its inhibitory effect by caffeine was examined. In addition, cell cycle distribution was also examined. MATERIALS AND METHODS: Two rat yolk sac tumor cell lines, NMT-1 and NMT-1R, with different radiosensitivities in vitro were used. The capacity for PLDR was examined using confluent-phase cells, and evaluated by calculating the recovery ratio. Inhibitory effect of caffeine on PLDR was examined with doses of 1, 5 and 10 mM. RESULTS: The capacity of PLDR in two cell lines reflected radiosensitivity. The recovery ratio after irradiation of 5 Gy was 2.8 in the radiosensitive NMT-1 and 5.2 in the radioresistant NMT-1R, and recovery reached its peak level at 6 h in both cell lines. The degree of inhibition of PLDR was weaker in NMT-1R than that in NMT-1 at the same dose level, and was correlated with reduction of G2-arrested cells by caffeine. CONCLUSIONS: The results of this study suggest that the capacity of PLDR may be one of the determinant factors for radiosensitivity in the two cell lines used, and the inhibitory effect of caffeine on PLDR was in part attributable to the modification of the cell cycle progression.

Animals↗
PubMed1998

Fine needle aspiration (FNA) of testicular germ cell tumours; a 10-year experience in a community hospital.

A retrospective reappraisal is made of the smears of 29 testicular germ cell tumors (TGCT) studied by FNA in which both orchiectomy specimens and histologic diagnoses were available. In 22 cases (75.86%) the yield was sufficient and contained cells suitable for cytologic diagnosis; in these 22 cases a diagnoses of malignancy was reached. In four cases (13.79%) the yield was sparse and a diagnostic cells were partially obscured by haemorrhage and necrosis; these cases were categorized as suspicious of malignancy. In these cases (10.34%) the yield was not suitable for cytologic evaluation because haemorrhage and necrosis hampered evaluation of diagnostic cells. The cytologic findings that enable a reliable diagnosis of TGCT are described and those cytologic features that may lead the less experienced cytopathologist into an erroneous diagnosis are discussed. Pure TGCT can be confidently diagnosed with FNA and mixed TGCT can be successfully diagnosed, although it is difficult to recognized every cytologic subtype observed in the histologic sections. Despite the advantages of FNA for the prompt diagnosis of TGCT, FNA can not fully replace the histologic diagnosis and should rather be considered as a helpful tool in the work-up of testicular tumours.

Adolescent↗
PubMed1994

Treatment of malignant testicular tumors in childhood: results of the German National Study 1982-1992.

The German Cooperative Protocol for treatment of testicular germ cell tumors in childhood registered 106 patients from January 1982 through February 1992. Sixty-one patients suffered from yolk sac tumors (YST); 25 patients from differentiated teratomas (TD); 19 patients from malignant teratomas of either intermediate (MTI), undifferentiated (MTU), or trophoblastic type (MTT), and 1 patient from a seminoma. A stratified chemotherapy based on stage and histology was administered in addition to unilateral orchiectomy: Standard chemotherapy consisted of four treatments with vinblastine, bleomycin, and cisplatinum. If viable tumor was suspected after two treatments with standard chemotherapy, a delayed explorative laparotomy was done. There were two options based on the histological findings: In case of complete tumor regression, the standard chemotherapy was continued. In case of incomplete tumor response, patients received a salvage chemotherapy consisting of three treatments with VP 16 (etoposide), ifosfamide, and cisplatinum. In addition three injections with VP 16 were given as a maintenance therapy. The following results were obtained: YST: 59 patients with stage I. Forty-nine patients were followed according to "wait and see" policy. Eight of these needed a delayed standard chemotherapy. The relapse free survival of all 61 patients in 100%. Median observation time is 49 months. TD: Twenty-five patients had stage I. No chemotherapy was given. The relapse free survival is 100%. Median observation time is 48 months. Malignant teratomas (MTI, MTU, MTT): 8 patients had stage I. Three of these received adjuvant chemotherapy and 5 lymphadenectomy without chemotherapy. All patients survived without relapse. Nine patients had stage II and received standard chemotherapy. Four of these patients had a delayed explorative laparotomy leading to a salvage therapy in two patients. All patients survived relapse free. Two patients had stage III. Of these 1 received standard chemotherapy and is well. One patient suffering from MTU stage IIIA died due to candida septicemia during salvage therapy. Median observation time of the entire group is 60 months.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Cytology of germ cell tumors: extragonadal, extracranial masses and intraoperative problems.

BACKGROUND: Germ cell tumors (GCTs) and their metastases may be found in numerous sites that are accessible to cytologic sampling, and many are responsive to chemotherapy. METHODS: The authors reviewed 20 examples of GCT cytology from 16 males and 3 females ranging in age from 1.5 to 61 years (median, 34 years). With two exceptions, one benign cystic ovarian teratoma in which intraoperative cytology was used to diagnose an associated adult-type carcinoma and one undescended testis in which seminoma presented as an abdominal mass, the material reviewed included no examples of primary gonadal GCT. RESULTS: The authors studied 7 primary and 13 metastatic GCTs; these studies were based on 13 in vivo aspirations, 4 intraoperative preparations, and 3 samples of body cavity fluids. All samples were correctly interpreted as malignant, and only one was incorrectly classified as a non-GCT malignancy. CONCLUSIONS: Clinical and cytologic findings are useful in the diagnosis of GCTs and their metastases. Incorrect interpretation of these neoplasms as poorly differentiated malignancies of other types may deprive the patient of effective chemotherapy. Air-dried, Romanowsky-stained smear material and cell block sections may contribute to the resolution of diagnostic dilemmas.

Adolescent↗
PubMed2000

Identification of a new missense mutation (Gly95Glu) in a highly conserved codon within the high-mobility group box of the sex-determining region Y gene: report on a 46,XY female with gonadal dysgenesis and yolk-sac tumor.

Leydig cells and Sertoli cells of the testes produce hormones that cause male differentiation, if receptors are present. The Y chromosomal SRY gene (sex determining Region Y gene) acts as TDF and is required for regular male sex determination. SRY represents a transcription factor belonging to the superfamily of genes sharing the HMG-box motif(high-mobility group-box), which acts as DNA binding region. Here, we describe a nonmosaic XY sex-reversed female with pure gonadal dysgenesis (46,XY karyotype, completely female external genitalia, normal Müllerian ducts, absence of Wolffian ducts, streak gonads) who harbored a yolk-sac tumor and was referred for the assessment of primary amenorrhea. Using genomic PCR analysis, a 423-bp PCR product, encompassing the HMG-box of the SRY gene, was amplified from the proposita, her father, and her three brothers, whereas no band was visible in the patient's mother and her three sisters. The PCR products were sequenced for mutations subsequently. A new de novo missense mutation within the HMG-box of the SRY gene was discovered in the proposita. A G is replaced by an A in codon 95 at position +284, resulting in the replacement of the nonpolar aminoacid glycine by the polar amino acid glutamate. The glycine at codon 95 is highly conserved between the family of HMG-box proteins and between species. This point mutation has not been described earlier and brings the total number of SRY mutations described so far to 36, each mutation being unique. This mutation was not detected in the patient's father and her male siblings. The present data provide further evidence to support the functional importance of the putative DNA binding activity of the SRY HMG-box domain.

Adult↗
PubMed1999

p53 mutation decreased radiosensitivity in rat yolk sac tumor cell lines.

PURPOSE: We reported that two established rat yolk sac tumor cell lines differ in their radiosensitivity by 1.7 fold, and the variation is most likely manifested by the differences seen in their apoptotic response. We investigated the relationship between radiosensitivity and p53 in these cell lines. METHODS AND MATERIALS: We assessed the status of p53 in cell lines by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and sequence analysis, and also analyzed protein expression of p53, p21, and bax as a function of time after irradiation to determine the signal transduction for p53 by immunoblotting. RESULTS: A band shift was observed only in exon 7 for the radioresistant NMT-1R cells and no band shift was detected for the radiosensitive NMT-1 cells. A band shift was confirmed also at the mRNA level. Exon 7 of p53 DNA showed a three base substitution of DNA at codon 267 to 268. Expression of p53, p21, and bax proteins in NMT-1R cells did not change after 10 Gy irradiation; however, in NMT-1 cells, the expression of these proteins was increased from 1-12 h after irradiation. CONCLUSION: A loss of p53 function by radiation-induced mutation of p53 decreased the radiosensitivity in these cell lines.

Animals↗
PubMedDate not supplied

Hyperthermia-induced apoptosis in two rat yolk sac tumor cell lines with different radiothermosensitivity in vitro.

We investigated cell susceptibility to hyperthermia-induced apoptosis in two rat yolk sac tumor cell lines (RYSTs) and attempted to correlate this with the known potentially relevant molecular determinants of apoptosis, p53 protein status, Bcl-2 family of proteins and heat shock proteins (Hsp). Parent cell line, NMT-1 (carrying wild-type p53 gene) was radiosensitive but thermoresistant compared to the variant cell line, NMT-1R (mutated type p53), which was isolated from NMT-1 by repeated radiation exposure. Induction of apoptosis by hyperthermia at 43 degrees C was morphologically detected in both RYSTs using hematoxylin and eosin, and TUNEL staining and additionally confirmed by DNA ladder formation (the cleavage of DNA into oligonucleosomal fragments). Western blot analysis showed an increase in expression of p53, p21WAF1/CIP1, Hsp70 proteins in both cell lines after heat-shock at 43 degrees C for 30 min. Hsp90 expression increased in NMT-1 but was not affected by heating in NMT-1R cells, whereas hyperthermia exerted no effect on the endogenous expression of Bax. Bcl-2 protein could not be detected in either RYST. These results suggest that hyperthermia induced apoptosis in both NMT-1 and NMT-1R and apoptosis in RYSTs may be independent of p53-dependent signaling pathway.

Animals↗
PubMed1994

Management of yolk sac tumor of the testis in children.

Yolk sac tumor (YST) is the most common form of malignant testicular tumor in infancy and children. However, there is no general agreement on its treatment regimen due to its rare occurrence. From 1978 through 1990, 30 cases of YST of the testis were treated at Chang Gung Children's Hospital. Thirteen (43.3%) occurred in the right testis and 17 (56.7%) in the left. Age at operation ranged from six months to five years with a mean of 1.79 years. All patients received an orchidectomy as their initial treatment. Eighteen patients with stage I disease were treated by orchidectomy alone. Fourteen (77.8%) of them were free of disease, two patients who had recurrence with retroperitoneal metastasis were successfully treated with chemotherapy. The remaining two patients died of metastasis. Seven patients with stage II disease and five with stage III disease were treated with combination chemotherapy, irradiation or debulking operation following orchidectomy. Four stage II patients (57.1%) and one stage III patient (20%) showed no evidence of disease at the time of follow-up. It was concluded that for stage I disease, orchidectomy alone followed by strict monitoring of alpha- fetoprotein achieved an 89% disease-free survival rate. Retroperitoneal node dissection or routine chemotherapy added no benefit to survival. For stage II or III disease, chemotherapy or irradiation is needed to obtain a better outcome.

Child, Preschool↗
PubMed1997

Expression of CD30 and CD30 ligand in cultured cell lines from human germ-cell tumors.

Embryonal carcinoma (EC) cells are the multipotent stem cells of human teratocarcinomas. EC cell lines isolated from human testicular teratocarcinomas retain pluripotentiality and show cell-surface marker phenotype and growth characteristics similar to those of primate embryonic stem cells. CD30, a member of the tumor necrosis factor superfamily of cytokine receptors, is expressed on the surface of human EC cells, but little is known regarding its function or the expression of its ligand in this context. Northern blot analysis, reverse transcriptase-PCR, and immunoprecipitation were used to study the expression of CD30 ligand and CD30 in cell lines representing multipotent and nullipotent EC as well as yolk sac carcinoma. Antibodies, recombinant CD30-Fc, and recombinant CD30 ligand were used in bioassays to assess the ability of exogenous CD30 ligand to promote the growth of multipotent human EC stem cells. Nullipotent and multipotent human EC cells, but not yolk sac carcinoma, expressed surface CD30, as demonstrated by immunoblotting and immunofluorescence; in multipotent cells, expression was decreased during differentiation induced by retinoic acid. Transcripts for CD30L were found at high levels in a yolk sac carcinoma cell line by Northern analysis and reverse transcriptase-PCR and were present at lower levels in EC cells as well. Immunoprecipitation confirmed expression of CD30 ligand protein in yolk sac carcinoma and in nullipotent embryonal carcinoma. Antibodies with CD30 cross-linking activity failed to promote the growth of multipotent EC cell line GCT 27 X-1. Anti-CD30 ligand antibodies and CD30-Fc both failed to block the promotion of EC cell growth induced by yolk-sac cell culture supernatants or feeder-cell monolayers. CD30 ligand is expressed in cell lines representative of human yolk sac carcinoma and nullipotent embryonal carcinoma. The membrane-bound cytokine may have an autocrine role in human EC stem-cell renewal, but other exogenous factors are required to maintain the growth of multipotent EC cells in vitro.

3T3 Cells↗
PubMedDate not supplied

Combined effect of hyperthermia at 42 degrees C and irradiation dose of 2 Gy on two rat yolk sac tumor cell lines with different radio-thermosensitivity in vitro.

BACKGROUND: Two rat yolk sac tumor cell lines, NMT-1 and NMT-1R, are of the same origin and of different sensitivity to irradiation and to heat. The aim of this study was to investigate the sensitivities of these two cell lines to combined treatments of low-dose irradiation at 2 Gy and hyperthermia at 42 degrees C. MATERIALS AND METHODS: The cell survival was assayed by soft agar clonogenic assay. After the survival curves of radiation alone and of heat alone at various temperatures were estimated, not only the effect of irradiation on heat, but the effect of heat on irradiation were evaluated with sequential treatments in both cell lines. These effects on survival curves were evaluated by the enhancement ratios at isosurvival levels of 37%, 10% and 1%, respectively. RESULTS: NMT-1 was more sensitive to radiation but more resistant to heat than NMT-1R. For 1% survival level, radiosensitivity in NMT-1 was 1.32 times that in NMT-1R, while thermal sensitivity at 42 degrees C in NMT-1R was 2.73 times that in NMT-1. For sequential treatment, thermosensitization by a radiation dose of 2 Gy in radiosensitive NMT-1 was greater than that in radioresistant NMT-1R. Following heat at 42 degrees C for 1 hour, increased radiosensitivity in NMT-1R was significant, whereas the same heat treatment produced an increase in the radiation sensitivity of NMT-1 with a reduction of the survival curve shoulder but with less slope modification. There was no difference in the surviving fraction in the time-course of a combination of heat and irradiation at various intervals within 6 hours for NMT-1 except for heating immediately after irradiation. However a significant increase in survival was observed when heat was applied more than 3 hours after 2 Gy irradiation for NMT1-R. CONCLUSION: These results from our cell lines with the same origin were useful for investigation into the interaction of irradiation with heat.

Animals↗
PubMed1999

Loss of heterozygosity, differentiation, and clonality in microdissected male germ cell tumours.

Testicular germ cell tumours (TGCTs) are heterogeneous neoplasms with different histological patterns and malignant potential. The aim of this study was to determine whether the main TGCT subtypes (seminoma, embryonal carcinoma, yolk sac tumour, choriocarcinoma, and mature teratoma) are distinguished by their loss of heterozygosity (LOH) patterns and whether LOH typing can help to distinguish between clonal and multifocal development of different components in mixed TGCTs. In 76 tumours analysed for allelic losses at 25 chromosomal loci, different LOH patterns were found in distinct histological subtypes. A region around D18S543 frequently lost in yolk sac tumours could harbour one or more tumour suppressor genes. In 20 microdissected mixed tumours, losses of identical alleles in different histological components in 11 of 20 cases (over 50 per cent) were found, which is in favour of current histogenetic models of clonal TGCT development. Clonal losses were most often found at D13S317 (6 of 20 tumours). Two classes of allelic losses may therefore occur during TGCT development: clonal losses which are involved in early transformational events and others related to TGCT differentiation along different lines.

Adult↗
PubMed1999

Incidence of testicular germ-cell malignancies in England and Wales: trends in children compared with adults.

The incidence of testicular cancer has been increasing markedly in most industrialised countries. This rise is known to have affected young adults, but it is less clear whether it has affected other age groups, particularly children. We used data from the National Cancer Registry file at the Office of National Statistics (ONS) and the National Registry of Childhood Tumours to examine trends in testicular germ-cell malignancies overall in England and Wales from 1962 to 1990 and in children from 1962 to 1995. The incidence of testicular cancer at all ages rose by 3.4% (95% CI 3.3-3.6%) per annum from 1962 to 1990. A similar rise in the incidence of germ-cell malignancies occurred during the years for which histological information was available in the ONS files, 1971-1989 (3.4%; 3.1-3.6%), to which both seminomas and non-seminomas contributed equally. The incidence of non-seminomas in adults rose in men under age 55 years and declined in older men, whereas there were increases in the incidence of seminomas in both young and older men. Cohort analysis at young ages showed a marked rise in the risk of germ-cell malignancies up to the cohort born in 1955-1959 but no further rise for those born subsequently. The rise in the incidence of these tumours in young adults was paralleled by a similar trend, although less marked, in children aged under 15 years (1.3% per annum; 0.2-2.5%). The increase in risk for children in this very large data set alongside the rise in young adults is compatible with the hypothesis that childhood and adult testicular germ-cell malignancies may have some common risk factors, presumably pre-natal.

Adolescent↗
PubMed1994

Testicular germ cell tumours of childhood in Denmark, 1943-1989: incidence and evaluation of histology using immunohistochemical techniques.

In the Danish Cancer Registry, 72 testicular tumours in boys younger than 15 years of age were recorded during the period 1943-1989 and material from 34 of these was retrieved from Danish departments of pathology. The histological types were evaluated and the role of immunohistochemical staining was analysed. The survival of the patients was correlated with the histological diagnoses, and changes in the incidence of testicular cancers in childhood were analysed. Twenty-nine of the 34 patients had germ cell tumours, which fell into two groups (infantile and pubertal) with distinct differences. The tumours of infancy usually presented before the age of 3 years and were either pure yolk sac tumours or teratomas. The tumours of puberty showed no morphological or immunohistochemical differences from adult germ cell tumours. In the infantile group, immunohistochemical staining confirmed the morphological evaluation but was not necessary for diagnosis. Patients in the infantile group seemed to have a better prognosis than adult patients, only one patient dying from his disease, whereas the pubertal patients seemed to have a prognosis similar to that of adult patients. The incidence of infantile testicular cancer in Denmark appears to have increased at almost the same rate as that observed in adult men, but due to the small numbers in infancy, this cannot be statistically substantiated. We conclude that the testicular germ cell tumours of infancy and puberty may arise from different precursor cells, but both groups seem to arise prenatally.

Adolescent↗