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At least 955 records · Page 53Linked to original sources
PubMed1997

Germ cell cancers in adult males are associated with a history of infantile pyloric stenosis.

Germ cell cancers (GCT) are the most common cancers of young men and are curable in at least 90% of cases. A number of aetiological factors have been identified which predispose to the development of these cancers, such as cryptorchidism and hernia. We report the association of GCT with infantile pyloric stenosis (IPS). The case records from 542 adult males with germ cell cancer arising from any site were screened for a history of pyloric stenosis requiring surgical treatment. Nine cases were observed (expected number = 2.168; chi squared = 21.5 (P < 0.001), standardised ratio = 4.15; 95% confidence interval 1.9-7.88). The recognition of rare associations of germ cell tumours may lead to the identification of genetic and environmental factors involved in their aetiology.

Adolescent↗
PubMed2002

Unusual intrathoracic location of a primary germ cell tumour.

The primary location of non-metastatic germ cell tumours of the chest is the anterior mediastinal compartment. Germ cell tumour arising from lung parenchyma is one of the rarest conditions in human and only a few cases of choriocarcinomas and yolk sac tumour have been reported to date. Here we report a case of intrapulmonary mixed type germ cell tumour, containing embryonal carcinoma, choriocarcinoma and yolk sac tumour elements. Diagnosis of the lesion was achieved by open thoracotomy and bulk of the tumour was resected by right upper lobectomy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Prognostic significance of histopathological subtypes in stage I pure yolk sac tumour of the ovary.

The correlation between histological subtype [endodermal sinus (ES), polyvesicular vitelline (PV), glandular (G) and hepatoid (H) subtypes] and the prognosis of pure yolk sac tumours (YSTs) of the ovary was investigated. From 1964 to 1989, 35 patients with YSTs were treated with primary surgery and adjuvant chemotherapy. The prevalence of histological subtypes was as follows: 14 patients had a single subtype, either ES (12) or G (2); 12 patients had two subtypes, ES+G (4), ES+PV (3), ES+H (4) or G+H (1); six patients had three subtypes, ES+P+H (4) or ES+G+H (2); and three patients had all four subtypes. Multivariate analysis showed that important predictors were FIGO stage, chemotherapeutic regimen and residual tumour size. However, for stage I, multivariate analysis showed that the histological subtype was a superior predictor to the subclassification of FIGO stage I, age or chemotherapeutic regimen (P = 0.03). Kaplan-Meier analysis showed that YSTs composed of an admixture of three or four subtypes was associated with a better prognosis than those composed of one or two subtypes (P < 0.01), other variables being constant.

Adolescent↗
PubMed2004

Characterisation of molecular events following cisplatin treatment of two curable ovarian cancer models: contrasting role for p53 induction and apoptosis in vivo.

The detailed molecular basis and determinants of in vivo tumour sensitivity to conventional anticancer agents remain unclear. We examined the cellular and molecular consequences of cisplatin treatment using two ovarian tumour xenograft models that had not been previously adapted to culture in vitro. Both xenografts were curable with clinically relevant multiple doses of cisplatin. Following a single dose of cisplatin (6 mg kg(-1) i.p.) growth delays of 25 and 75 days were obtained for pxn100 and pxn65, respectively. This difference in response was not due to differences in DNA damage. Pxn100 tumours had a functional p53 response and a wild-type p53 sequence, whereas pxn65 harboured a mutant p53 and lacked a functional p53 response. Microarray analysis revealed the induction of p53-regulated genes and regulators of checkpoint control and apoptosis in pxn100 tumours following cisplatin-treatment. By contrast, there was no p53-dependent response and only limited changes in gene expression were detected in the pxn65 tumours. TUNEL analysis demonstrated high levels of apoptosis in the pxn100 tumours following cisplatin treatment, but there was no detectable apoptosis in the pxn65 tumours. Our observations show that a marked in vivo response to cisplatin can occur via p53-dependent apoptosis or independently of p53 status in human ovarian xenografts.

Adenocarcinoma↗
PubMed1999

Human germ cell tumours: expression of gamma-glutamyl transpeptidase and sensitivity to cisplatin.

Previous studies have shown that the enzyme-glutamyl transpeptidase (GGT) is essential for the nephrotoxicity of cisplatin. This study was designed to determine whether GGT activity is necessary for the therapeutic effect of the drug. The relationship between GGT expression and clinical response to platinum-based chemotherapy was examined in 41 human germ cell tumours. Sections of formalin-fixed, paraffin-embedded tumours were immunohistochemically stained with an antibody directed against human GGT. There was no expression of GGT in any of the 17 seminomas or four dysgerminomas; whereas, 12/12 ovarian yolk sac tumours and 4/4 embryonal carcinomas of the testis were GGT-positive. In stage I tumours fewer tumour cells expressed GGT than in later stage tumours. In four germ cell tumours of mixed histology, the seminomatous and dysgerminoma areas were GGT-negative while the areas of the tumour with yolk sac or embryonal histology contained GGT-positive tumour cells. The patients with seminomas or dysgerminomas who were treated with cisplatin-based chemotherapy, all had a complete response despite the absence of GGT expression in these tumours. Fifteen of the 16 patients with yolk sac or embryonal carcinomas received cisplatin-based chemotherapy following surgery. Twelve had a complete response, while three failed to respond to platinum-based therapy. There was no correlation between the level of GGT-expression and response to therapy in this group. Three of the four patients with tumours of mixed histology were treated with cisplatin-based therapy, and had a complete response. Therefore, expression of GGT is not necessary for the therapeutic effect of cisplatin in germ cell tumours. The results from this study suggest that systemic inhibition of GGT would inhibit the nephrotoxic side-effect of cisplatin without interfering with its activity towards germ cell tumours.

Adolescent↗
PubMed1999

Ovarian hepatoid yolk sac tumours: morphological, immunohistochemical and ultrastructural features.

AIM: The clinicopathological, immunohistochemical and ultrastructural features of two ovarian hepatoid yolk sac tumours (H-YST) from our files are reviewed. METHODS AND RESULTS: Using avidin-biotin-peroxidase complex technique, the immunoprofile of these tumours was compared to that of a classic yolk sac tumour and to that previously reported for hepatocellular carcinomas. The clinicopathological and morphological features of our cases are similar to the seven previously reported ovarian cases. This rare germ cell tumour occurs in young females (mean age = 17.6 years) and presents most commonly with abdominal pain and a large ovarian mass (average size = 140 mm). Histologically, the tumours display a striking resemblance to hepatocellular carcinoma. The absence of an associated typical pattern of yolk sac tumour or other germ cell neoplasm may make it difficult to recognize the germ cell origin of this lesion. Our cases demonstrated positive staining for alpha-fetoprotein and alpha-1-antitrypsin. In addition, there was immunoreactivity with polyclonal carcinoembryonic antigen (CEA) antiserum in a canalicular pattern, focal staining for inhibin, oestrogen and progesterone receptors and absence of immunoreactivity for CK7 that contrasts with the immunophenotype of a usual yolk sac tumour. CONCLUSIONS: Ovarian H-YST and hepatocellular carcinoma share a similar immunoprofile. Ovarian H-YST is a highly aggressive tumour, most patients exhibit recurrence or die of disease within 2 years of diagnosis.

Adolescent↗
PubMed1997

Selective cytotoxicity of two rodent T cell lymphomas to rat yolk sac tumours involves a retroviral envelope protein expressed by the lymphoma.

A Gross virus induced rat T cell lymphoma G1-Tc1 and a Moloney virus induced mouse T cell lymphoma YAC-1 are shown to exert a strong cytotoxic activity against rat yolk sac tumours but not to various types of rat, mouse or human normal cells or tumour cell lines including carcinomas, sarcomas, lymphomas and gliomas. Both lymphomas are CD3+, CD4-, CD8- and T-cell receptor (TCR) alpha beta +. The cytotoxicity was not MHC restricted or dependent on the density of MHC class I of the target cells, and the mouse lymphoma killed the rat yolk sac tumour target. The cytotoxic action was fast and up to 80% specific killing was observed in 4-h 51Cr release assays. A rat B cell hybridoma was established from a Wistar/Furth (WF) rat immunized with the syngeneic lymphoma G1-Tc1 producing an immunoglobulin (Ig)G2c monoclonal antibody (MoAb) 1F2. This binds to the lymphomas G1-Tc1 and YAC-1 and also to a murine non-cytolytic Rauscher lymphoma RMA, but not to any other of several rat, mouse or human cell types tested. The 1F2 completely inhibited the killing of rat yolk sac tumours by the two cytolytic lymphomas, but did not interfere with the killing mediated by natural killer (NK) cells or cytolytic lymphokine-activated killer (LAK) cells. Immunochemical analysis of solubilized cell membranes of the lymphoma G1-Tc1 demonstrates that the 1F2 antibody recognizes an epitope on a retroviral gp 70 envelope protein. This indicates that a retroviral protein is involved in the lytic activity of the two lymphomas.

AKR murine leukemia virus↗
PubMed1997

Evaluation of primary standard cisplatin-based chemotherapy for clinical stage II non-seminomatous germ cell tumours of the testis.

OBJECTIVE: To evaluate the use of primary cisplatin-based chemotherapy before retroperitoneal lymph node dissection (RPLND) in patients with clinical stage II non-seminomatous germ cell tumours of the testis. PATIENTS AND METHODS: Between 1984 and 1992, 55 patients with clinical stage II testicular cancer (12 with stage IIA. 33 stage IIB and 10 stage IIC disease) were treated at Institut Gustave Roussy with primary chemotherapy using three conventional regimens including cisplatin. Patients were assessed 4 weeks after the end of chemotherapy and depending on the response, underwent RPLND; the overall survival and disease progression were monitored. RESULTS: Sixteen (29%) patients achieved a sustained complete remission after chemotherapy only, while 30 (55%) patients required subsequent RPLND for persistent residual tumour masses: nine other patients obtained a clinical partial remission. Six patients who initially had achieved either a clinical complete response (three) or a surgical complete response (one) or a clinical partial response (two) subsequently relapsed. Overall, 52 of 55 (95%) patients remained free of disease 33 to 111 months after the end of treatment. CONCLUSION: These results show that primary cisplatin-based chemotherapy can effect a cure of the tumour in all subgroups of patients with stage II disease.

Adolescent↗
PubMed1998

Immortalized rat proximal tubule cells produce membrane bound and soluble megalin.

Megalin (gp330), a glycoprotein receptor found on renal proximal tubule cells and several other epithelial cells, is deduced to be a type I integral membrane protein, but may also exist as a cell surface form lacking a cytoplasmic domain. Furthermore, soluble megalin products have been detected in urine, and in culture medium of a rat yolk sac carcinoma cell line, combined with receptor associated protein (RAP). Permanent renal cell lines expressing megalin were unavailable until the recent description of two immortalized rat proximal tubule cell lines (IRPTC). The present study demonstrated megalin on IRPTC surface by immunofluorescence, without surface staining for RAP, which was, however, readily detected within cells. Antibodies to ectodomain megalin epitopes immunoprecipitated megalin products both from cell lysates and culture medium, whereas antibodies to cytoplasmic domain epitopes precipitated megalin only from lysates. Western blots showed two major megalin products in medium, a prominent band at approximately 200 kDa, and a fainter band above 400 kDa, slightly below intact megalin in cell lysates. Anti-receptor associated protein antibodies immunoprecipitated megalin from IRPTC lysates, but not from media. We propose that portions of megalin are spontaneously produced by IRPTC, probably either by cleavage in the ectodomain or release of forms lacking a cytoplasmic domain.

Animals↗
PubMed2002

Primary endodermal sinus (yolk sac) tumour of the liver.

Primary endodermal sinus tumour of the liver is an extremely rare neoplasm. A 37-year-old man presented with a mass in the left lobe of the liver and a raised serum alpha-fetoprotein concentration. A left hepatic lobectomy was performed. Histological examination revealed an endodermal sinus tumour of the liver. There was no evidence of an extrahepatic primary source.

Adult↗
PubMed1996

Megalin-mediated endocytosis of transcobalamin-vitamin-B12 complexes suggests a role of the receptor in vitamin-B12 homeostasis.

Kidney cortex is a main target for circulating vitamin B12 (cobalamin) in complex with transcobalamin (TC). Ligand blotting of rabbit kidney cortex with rabbit 125I-TC-B12 and human TC-57Co-B12 revealed an exclusive binding to megalin, a 600-kDa endocytic receptor present in renal proximal tubule epithelium and other absorptive epithelia. The binding was Ca2+ dependent and inhibited by receptor-associated protein (RAP). Surface plasmon resonance analysis demonstrated a high-affinity interaction between purified rabbit megalin and rabbit TC-B12 but no measurable affinity of the vitamin complex for the homologous alpha 2-macroglobulin receptor (alpha 2MR)/low density lipoprotein receptor related protein (LRP). 125I-TC-B12 was efficiently endocytosed in a RAP-inhibitable manner in megalin-expressing rat yolk sac carcinoma cells and in vivo microperfused rat proximal tubules. The radioactivity in the tubules localized to the endocytic compartments and a similar apical distribution in the proximal tubules was demonstrated after intravenous injection of 125I-TC-B12. The TC-B12 binding sites in the proximal tubule epithelium colocalized with megalin as shown by ligand binding to cryosections of rat kidney cortex, and the binding was inhibited by anti-megalin polyclonal antibody, EDTA, and RAP. These data show a novel nutritional dimension of megalin as a receptor involved in the cellular uptake of vitamin B12. The expression of megalin in absorptive epithelia in the kidney and other tissues including yolk sac and placenta suggests a role of the receptor in vitamin B12 homeostasis and fetal vitamin B12 supply.

Animals↗
PubMed1999

Malignant ovarian germ cell tumours -- a survival and prognostic analysis.

The medical records and histopathology of all ovarian germ cell tumours (OGCT) in a tertiary centre between 1980 and 1996 were reviewed. Response, overall survival (OS), relapse-free survival (RFS) and prognostic factors were analysed. Sixty-seven patients with OGCT were identified and treated, including 33 dysgerminomas, 18 immature teratomas, 10 endodermal sinus tumours, and 6 mixed tumours. Fifty-three patients (79%) received conservative surgery, 24 (36%) had residual disease post-primary surgery, and 43 (64%) had chemotherapy. Complete response was achieved in 62 patients (93%), 4 out of 5 patients who relapsed were successfully salvaged; OS and RFS at 5 years were 89% and 76%, respectively. Advancing stage of disease was the only significant adverse prognostic factor (p = 0.0001 for OS, and 0.0003 for RFS at 5 years). Out of 44 women with the potential to conceive following treatment, there were 16 successful pregnancies. None of the children born subsequent to the chemotherapy were reported to have any congenital abnormalities. The review indicates a high cure rate in OGCT with combined surgery and chemotherapy and that conservative surgery and preservation of fertility are feasible.

Adolescent↗
PubMed1996

An interaction of cisplatin and radiation in two rat yolk sac tumour cell lines with different radiosensitivities in vitro.

We investigated the interaction of cisplatin and radiation in two rat yolk sac tumour cell lines with different radiosensitivities in vitro. The effects were assessed by clonogenic assay. D0 for the radiosensitivity of the radioresistant variant cell line, NMT-1R was 139 cGy, which was 1.3 times larger than that for the parent radiosensitive cell line, NMT-1 (D0 = 107 cGy). The concentration of cisplatin required to reduce colony formation by 50% at 1 h treatment (ID50 of cisplatin) was 0.25 microgram/ml for NMT-1, whereas that for NMT-1R was 1.0 microgram/ml. Cisplatin potentiation of radiation sensitivity was manifested by the decrease in the slope of the radiation dose-response curve. D0's for NMT-1 and NMT-1R were 83 and 100 cGy in combined treatment with ID50 of cisplatin immediately before radiation. The enhancement ratios of cisplatin were therefore 1.30 for NMT-1 and 1.39 for NMT-1R respectively in D0. No different enhancement ratio for cisplatin was observed in the time course of combination treatment with cisplatin and radiation within the interval of 6 h. There was no clear change in cell cycle distribution within 6 h after treatment with ID50 of cisplatin for both cell lines. In conclusion, cisplatin had a synergistic effect on both cell lines which was independent of the time course and sequence in combination with radiation within 6 h.

Animals↗
PubMed1996

A radioresistant variant cell line, NMT-1R, isolated from a radiosensitive rat yolk sac tumour cell line, NMT-1: differences of early radiation-induced morphological changes, especially apoptosis.

A radioresistant variant cell line, NMT-1R, was isolated by repeated radiation exposure of a radiosensitive rat yolk sac tumour cell line, NMT-1, producing alpha-fetoprotein, with the potential for lymphatic metastasis in the inbred Wistar rat. Cultured NMT-1R cells showed more cobblestone-like appearances, although the morphological features were almost the same as radiosensitive NMT-1 cells reported previously. The doubling time of NMT-1R cells was 13.6 h, being shorter than that of NMT-1 cells (16.0 h). For NMT-1R cells, D0 for radiation sensitivity was 165 +/- 3 cGy, 1.7 times as large as for NMT-1 cells. The extrapolation number, n, was 1.48 +/- 0.17 for NMT-1R cells although that for NMT-1 cells was 1.08 +/- 0.15. The surviving fractions at 2 Gy (SF2) were 0.42 for NMT-1R cells and 0.28 for NMT-1 cells. The population of G2-M phase for NMT-1R cells was larger than for NMT-1 cells (32.5 versus 26.8%) in exponentially growing cells. Although a clear G2 delay was observed after irradiation with a dose of 182 cGy for both cell lines, NMT-1R cells had a shorter recovery time from G2 block than NMT-1 cells, G1 arrest was observed in NMT-1 cells. NMT-1 cells showed much higher incidence of early morphological changes, especially apoptosis, after irradiation with a dose > 500 cGy compared with NMT-1R cells.

Animals↗
PubMed1998

Cytotoxic effect of paclitaxel (taxol) either alone or in combination with irradiation in two rat yolk sac tumour cell lines with different radiosensitivities in vitro.

PURPOSE: To investigate the differences between two rat yolk sac tumour cell lines with different radiosensitivities in paclitaxel sensitivity and in the sensitizing effects of paclitaxel in combination with irradiation. MATERIALS AND METHODS: NMT-1 is a parent radiosensitive cell line and NMT-1R is a variant radioresistant cell line. RESULTS: Clonogenic assay demonstrated almost the same paclitaxel sensitivity with Do of 5.15 nM in NMT-1 and 5.02 nM in NMT-1R. Many apoptotic cells and DNA ladder formations were observed at 24 h after exposure to paclitaxel in both cell lines. The incidence of DNA fragmentation after 24 h exposure to 20 nM paclitaxel was 12.4 +/- 3.3% for NMT-1, and 13.0 +/- 1.9% for NMT-1R. Paclitaxel showed a supra-additive effect in combination with irradiation in both cell lines at 12 h after paclitaxel treatment only when the accumulation of cells in the G2/M phase reached its peak. CONCLUSIONS: Paclitaxel had the same cytotoxic effect in two cell lines with different radiosensitivity due to the induction of apoptosis. A supra-additive effect to radiation was observed with 12 h pretreatment in both cell lines. Paclitaxel may be effective for tumours with a component of different radiosensitivity in combination with irradiation.

Animals↗
PubMed2001

Expression of hMLH1 and hMSH2 and assessment of microsatellite instability in testicular and mediastinal germ cell tumours.

The aim of this study was to investigate DNA mismatch repair deficiency in male germ cell tumours. We analysed the expression of two mismatch repair proteins, human mutL homologue 1 (hMLH1) and human mutS homologue 2 (hMSH2), and evaluated the frequency of microsatellite instability with 10 mononucleotide and two dinucleotide repeat sequences, in 39 paired tumour/normal DNA samples obtained from 17 testicular and two mediastinal germ cell tumours. In all 19 cases, hMLH1 and hMSH2 both showed nuclear immunolocalization in invasive and testicular in-situ tumours. In non-neoplastic seminiferous tubules, hMLH1 was expressed only in premeiotic germ cells, while hMSH2 was seen in all stages of spermatogenesis. Genetic analysis of dinucleotide markers revealed loss of heterozygosity in one of two testicular yolk sac tumours at D18S58 and an allelic shift at D2S123 in two of three testicular embryonal carcinomas, while none of the 12 seminomas exhibited a genetic abnormality at these loci. No abnormalities were demonstrated with the 10 mononucleotide markers. The two mediastinal germ cell tumours showed no genetic instability or allelic loss with all 12 markers. We suggest that genetic alterations as assessed by microsatellite analysis in germ cell tumours may reflect tissue maturation and phenotypic differentiation rather than tumour progression. In addition, we suggest that hMLH1 and hMSH2 genes may not be implicated in the genesis of germ cell tumours.

Adaptor Proteins, Signal Transducing↗