The need for microdissectional tumor cell preparation during the molecular genetic analysis of prostate cancer.

For clinically localized prostate cancer, recent studies strongly indicate that the determination of p53 inactivation allows the identification of a highly aggressive subgroup of prostatic tumors associated with decreased recurrence-free and long-term survival following radical prostatectomy. However, several questions regarding the determination of p53 alterations in prostate cancer, such as the poor correlation between immunohistochemistry and molecular genetic analysis, remain to be clarified. On the DNA level, p53 gene alterations have been identified in only up to 64% of tumors exhibiting immunohistochemically detected overexpression of the p53 oncoprotein.

Prognostic value of p27Kip1 and p21WAF/Cip protein expression in muscle invasive bladder cancer.

Two genes, namely p27Kip1 and p21WAF/Cip1 that reveal distinct structural homology, have been identified as inductors of cell cycle arrest at the G1-checkpoint to prevent entry of somatic cells into the S phase of the cell cycle when substantial DNA damage has occurred. It was demonstrated that the p21WAF/Cip1 gene is induced by pathways dependent and independent from a functionally intact p53 tumour suppressor protein. It has been suggested that decreased expression both of the p21WAF/Cip1 and p27Kip1 protein may contribute to the development of human malignancies due to loss of critical antiproliferative mechanisms.

Docetaxel and cisplatin: an active regimen in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck. Results of a phase II study of the EORTC Early Clinical Studies Group.

Background: Docetaxel and cisplatin are among the most active antitumor agents in head and neck cancer, and phase I studies found the combination of the two drugs to be feasible. The EORTC ECSG performed a multicenter phase II study in patients with locally advanced, recurrent or metastatic squamous cell carcinoma of the head and neck to evaluate the antitumor efficacy and toxicity of this combination.

Patients And Methods: Eligibility criteria included written informed consent, a WHO performance status < 2, life expectancy of > 12 weeks, and adequate bone marrow, liver and renal function.

Advanced head and neck cancer and clinical experience of an effective new agent: docetaxel.

Introduction: Docetaxel is a taxoid cytotoxic agent known to have considerable clinical activity in a broad range of malignancies. A series of phase I/II studies have been performed to elucidate its toxicity and antitumor activity in advanced squamous cell carcinoma of the head and neck. DOCETAXEL AS FIRST-LINE MONOTHERAPY: Docetaxel administered at 100 mg/m2 as a 1-hour infusion every 3-4 weeks initiated an overall response of 27-42% for a duration of 5-6.

Analysis of the cyclin-dependent kinase inhibitor p27Kip1 in muscle invasive bladder cancer.

It has been suggested that a deregulated cell cycle control contributes to the development of human malignancies due to the loss of critical antiproliferative mechanisms. The cell cycle is controlled at two checkpoints, one at the G1-S and another at the G2-M transition. Several genes including the structurally related p21WAF/CIP1 gene, the downstream mediator of the p53 tumor suppressor gene, and the p27Kip1 gene have been identified as inducers of cell cycle arrest at the G1 checkpoint when substantial DNA damage has occurred to avoid further replication of the altered genome.

A questionnaire-based outcome analysis of the Stamey bladder neck suspension procedure for the treatment of urinary stress incontinence: the Hannover experience.

Objectives: To evaluate the long-term continence rate, including subjective satisfaction and therapy-associated morbidity, of patients undergoing Stamey bladder neck suspension.

Patients And Methods: Eighty-five women (median age 55 years, range 30-85) with urinary stress incontinence treated by Stamey bladder neck suspension at our institution between 1987 and 1995 were evaluated using an anonymous questionnaire over a mean (range) follow-up of 61 (13-93) months.

Results: Of the 85 patients, 44 (52%) reported an improvement in clinical symptoms at the evaluation and 29 (34%) were completely continent after the Stamey procedure.

The prognostic value of p53 for long-term and recurrence-free survival following radical prostatectomy.

In the present study, 76 specimens (T1-T4) from 76 randomly selected patients undergoing radical prostatectomy at Hannover University as well as in the Josef Hospital Regensburg (13 patients) between 1980 and 1992 for whom tissue sections for immunohistochemical investigation were available, were investigated for different biological and clinical characteristics as predictors for long-term and recurrence-free survival: age, depth of tumour infiltration, histological grade, lymph node status, as well as overexpression of the p53 protein (monoclonal antibody DO-1). After a median follow-up of 50 months, 6 of 18 patients (33%) with more than 20% of tumour cells stained positively for p53 died from tumour progression compared with 9 of 58 patients (16%) with less than 20% of tumour cells positive for p53. During univariate analysis, p53 overexpression (P = 0.

The IgG Fc receptor family.

IgG immune complexes are of central importance in the humoral immune system and strongly implicated in the pathogenesis of hematologic and rheumatic autoimmune disorders. Cross-linking of receptors for the Fc domain of IgG antibodies (FcgammaRs) triggers a wide variety of effector functions including phagocytosis, antibody-dependent cellular cytotoxicity, and release of inflammatory mediators, as well as immune complex clearance and regulation of antibody production. In this way, FcgammaR provide an essential feedback between the humoral and cellular immune response.

Expression of E-cadherin in primary prostate cancer: correlation with clinical features.

Objective: To correlate the immunohistochemically detected loss of E-cadherin expression with patient age, clinical and biological variables, and to investigate the prognostic value of these variables for the relapse-free and overall survival of patients with different stages of newly diagnosed prostate cancer.

Patients And Methods: Sixty-seven patients (median age 63 years, range 48-78) undergoing radical prostatectomy for the treatment of primary prostate cancer were assessed to determine whether age, tumour stage, histological grading, serum levels of prostate specific antigen and prostatic acid phosphatase, regional lymph node status and E-cadherin expression were prognostic factors for relapse-free and overall survival.

Results: With a median (range) follow-up of 54 (3-193) months, there was no independent prognostic value of decreased E-cadherin expression for the long-term or recurrence-free survival of patients, using a threshold value of 40% for the relative amount of positively stained tumour cells, or for any other threshold value calculated (25%, 60% or 75%).

The MXI1 tumor suppressor gene is not mutated in primary prostate cancer.

For prostate cancer, allelic deletions from the long arm of chromosome 10 (#10q23-25), the locus of the putative tumor suppressor gene MXI1 (#10q24-25), have been identified as a frequently occurring genetic event. During the development of several human malignancies, the c-myc proto-oncogene has been identified to enhance cellular transformation, mitogenesis and cell proliferation. The MXI1 gene, belonging to the helix-loop-helix (bHLH) gene family, was demonstrated to display tumor suppressor function by antagonizing c-myc induced transcriptional activities.

Treatment of brain metastases in patients with testicular cancer.

Purpose: Despite improved cure rates for patients with metastatic testicular cancer with cisplatin-based combination chemotherapy, patients who develop brain metastases are generally considered to possess a poor prognosis. This report summarizes the long-term results in 44 patients with brain metastases from testicular cancer treated between 1978 and 1995 at Hannover University Medical School.

Patients And Methods: Histologically, 42 patients (95%) had a nonseminomatous germ cell cancer and two patients (5%) a seminoma.

Evaluation of long-term toxicity after chemotherapy for testicular cancer.

Purpose: The current study evaluates the extent and reversibility of late sequelae after chemotherapy in longterm survivors of testicular cancer. The influence of therapy and patient characteristics and the relationship between different toxicities are assessed.

Patients And Methods: Ninety patients with a median age of 28 years (range, 19 to 53) and a median followup time of 58 months (range, 15 to 159) participated in the clinical examinations, a personal interview, and technical investigations.

Alterations of the p53 tumor suppressor gene in carcinoma in situ of the testis.

Background: Carcinoma in situ (CIS) is regarded as the precursor of all histologic variants of testicular germ cell tumors except spermatocytic seminoma. For a variety of human malignancies, alterations of the p53 tumor suppressor gene have been identified as prognostic factors for a poor clinical course. Discussions of the occurrence of p53 gene alterations in testicular carcinoma have been controversial.

Endocrinological late effects after chemotherapy for testicular cancer.

Type and extent of endocrinological alterations were studied in long-term disease-free survivors after cisplatin-based chemotherapy for testicular cancer. A total of 63 patients with a median age of 30 (19-53) years, and median follow-up of 42 (16-128) months were included. Elevated serum follicle-stimulating hormone (FSH) levels were found in 63% of patients, 24% showed pathologically elevated luteinising hormone (LH) levels with normal and 10% with subnormal testosterone levels.

Exposure to vinblastine modulates beta 1 integrin expression and in vitro binding to extracellular matrix molecules in a human renal carcinoma cell line.

Solitary stroma-invading tumor cells expressing the ATP-binding cassette transporter P-glycoprotein have been reported to be associated with a significantly higher incidence of vessel invasion and lymph node metastases. In contrast to P-gp-mediated multidrug resistance (MDR) which has become well characterized over the last decade, little is known about further morphological and functional alterations in drug-resistant tumor cells. Binding of malignant cells to components of the extracellular matrix mediated by beta 1 integrins has been suggested to play a substantial role in the metastatic cascade.

Expression of stem-cell factor and its receptor c-kit protein in normal testicular tissue and malignant germ-cell tumours.

The proto-oncogene c-kit and its ligand stem-cell factor (SCF) may play an important role in the development of normal and malignant testicular tissue. This study investigates the presence of SCF and c-kit protein in 32 orchiectomy specimens of patients with testicular cancer, in 5 specimens of normal testicular tissue and in three established non-seminomatous germ-cell cancer cell lines (H12.1, H32, 577ML) by an immunohistochemical approach.

Secondary Raynaud's phenomenon and other late vascular complications following chemotherapy for testicular cancer.

182 patients treated with cisplatin-based chemotherapy for testicular cancer at Hannover University Medical School who were in complete remission (CR) for more than 1 year after therapy were randomly selected for the evaluation of late vascular toxicity. 90 patients with a mean age of 28 years (19-53) and a median follow-up of 57.9 months (15-159) participated in this examination.

No synergistic activity of epirubicin and interferon-alpha 2b in the treatment of hepatocellular carcinoma.

Single-agent activity for anthracyclines reflected by response rates of 10%-30% has been reported in patients with advanced hepatocellular carcinoma (HCC). Preclinical data indicate that alpha-interferon could enhance the cytotoxic activity of the anthracycline Adriamycin or its analog epirubicin. In a phase I/II study, 31 patients with biopsy-proven inoperable HCC were treated with interferon-alpha 2b given s.

p53 immunohistochemistry as an independent prognostic factor for superficial transitional cell carcinoma of the bladder.

Although patients with superficial bladder cancer (Ta, T1) have a generally good prognosis, those patients who develop muscle-invasive tumours or metastatic disease at recurrence do poorly clinically. In the current study 69 patients undergoing complete transurethral resection for superficial transitional cell cancer of the bladder were investigated for different clinical and biological characteristics as possible prognostic factors: age, sex, performance of instillation therapy and immunohistochemical determination of mutational inactivation of p53 tumour-suppressor gene (monoclonal antibody PAb 1801) as well as immunohistochemical determination of the proliferation rate by staining for PCNA (proliferating cell nuclear antigen) (monoclonal antibody PC 10). After a median follow-up of 45.

Treatment of testicular cancer and the development of secondary malignancies.

Purpose: Secondary neoplasia represents one of the worst possible long-term complications of therapy for testicular cancer, frequently leading to death in patients cured of the primary malignancy. The frequency and importance of secondary malignant disease will be reviewed.

Methods: The international literature was screened for reports concerning secondary solid cancers or leukemias in patients treated with chemotherapy or radiotherapy for malignant germ cell tumors.

Bilateral metachronous testicular germ cell tumors occurring in two non-twin brothers. Case report and review of the literature.

We report here the familial occurrence of bilateral testicular germ cell tumors in 2 non-twin brothers, developing after an interval of 16 and 4 years, respectively. To our knowledge, this is the first report on the occurrence of metachronous and bilateral testicular tumors in non-twin brothers.

The role of granulocyte-macrophage colony-stimulating factor in the treatment of germ cell tumors. German Testicular Cancer Study Group.

Hematopoietic growth factors, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), may gain increasing importance in the treatment of patients with malignant germ cell tumors. For patients with far advanced testicular cancer, who only have a chance of long-term cure in the range of 40% to 50% by standard induction chemotherapy, the German Testicular Cancer Study Group has shown that the application of GM-CSF after PEI chemotherapy has allowed the increase of dose intensity of this three-drug regimen by a factor of 1.4.

Overexpression of the p53 oncoprotein in carcinoma in situ of the testis.

Carcinoma in situ (CIS) is regarded as the precursor lesion of testicular germ cell tumors. In adults CIS cells have also been described within the normal testicular tissue adjacent to mature teratomas with a frequency of 52-88%. These CIS-cells can be identified by immunohistochemical staining for "placental like alkaline phosphatase" (PLAP).

The anti-tumour activity of ifosfamide on heterotransplanted testicular cancer cell lines remains unaltered by the uroprotector mesna.

Ifosfamide is clinically used in combination chemotherapy regimens for the treatment of patients with high-grade lymphomas, sarcomas and metastatic germ cell tumours. In order to reduce the oxazophosphorine-related urothelial toxicity, sodium mercaptoethane sulphonate (mesna) is used in different schedules following the administration of ifosfamide. The proposed mechanism of mesna activity is the binding of toxic oxazaphosphorine metabolites such as acrolein in the urine of the patients.

Long-term gonadal toxicity after therapy for Hodgkin's and non-Hodgkin's lymphoma.

With the increasing cure rate of patients treated for Hodgkin's and non-Hodgkin's lymphoma, the evaluation of late effects on gonadal function remains an important issue. The gonadal function of relapse-free long-term survivors with high-grade non-Hodgkin's lymphoma (NHL) and Hodgkin's disease (HD) were studied; 24 of 119 patients with NHL treated between 1980 and 1990 and 66 of 364 patients with HD treated between 1975 and 1990 at Hannover University Medical School, who were younger than 45 years of age and in complete remission at the time of evaluation for at least 24 months after completion of therapy, were included into the analysis. Of 24 patients with NHL, 1/10 women (10%) and only 3/14 men (21%) showed signs of gonadal dysfunction.