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L Weissbach

Publications and source records attributed to L Weissbach.

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

Binding of myosin essential light chain to the cytoskeleton-associated protein IQGAP1.

The 190 kD human IQGAP1 protein, by virtue of its N-terminal calponin-homology domain, is found associated with the actin cytoskeleton, and is capable of cross-linking actin filaments. IQGAP1 complexes with several proteins, including the Rho family GTPases Cdc42 and Rac, as well as calmodulin. It was previously noted that one of the IQ motifs of IQGAP1 displays significant similarity to a myosin heavy chain IQ motif responsible for binding the calmodulin-related myosin essential light chain (ELC). Employing the yeast two-hybrid methodology as well as in vitro binding experiments, we present evidence that a truncated version of IQGAP1 can interact with the myosin ELC. This interaction may have significant consequences for various cellular processes that involve actomyosin contractility, and suggests that the biological targets of the ELC may not be restricted to the myosin heavy chain.

Actins↗
PubMed1998

Detection of an interleukin-1 intracellular receptor antagonist mRNA variant.

At least two versions of interleukin-1 receptor antagonist generated by alternative splicing are found intracellularly, but their functions remain poorly characterized. During studies aimed at characterizing the expression of these transcripts in human articular cartilage, we detected a variant cDNA species that contained an additional 171 nucleotides within the type I interleukin-1 intracellular receptor antagonist cDNA which interrupted the coding region. This mRNA variant was also found to be expressed in keratinocytes. Translation likely initiates at an alternate methionine codon than that utilized for the previously reported interleukin-1 intracellular receptor antagonist isoforms, suggesting that this mRNA variant encodes a novel polypeptide that may play a role in interleukin-1 signaling.

Alternative Splicing↗
PubMed1998

[Calculus formation after kidney pyeloplasty due to suture material].

We observed two patients with stone formation in the renal pelvis two and five years after pyeloplasty. In both cases there was no obstruction of the pyeloureteral junction detectable. We consider the use of Polyglactin (Vicryl) for the pelvis suture as reason for the stone formation. For stone removal we favourite an endoscopic procedure, in which a removal of residuums of the suture is even possible as the verification of the pyeloureteral junction.

Adult↗
PubMed1998

[In which marker-positive patients with germ cell tumors is residual tumor resection of value?].

We analyzed 33 patients with disseminated germ cell tumors (GCT) who underwent residual tumor resection (RTR) during the period from 1991-1997. The patients were marker positive prior to surgery were analyzed. The histopathological examination of the resected masses, the marker dynamics and the relapse-free respectively the progression free survival, were evaluated. The status differed at primary diagnosis: minimal disease n = 1, moderate disease n = 15, advanced disease n = 17. The patients received at average 8.5 cisplatin-containing cycles of polychemotherapy. Only 11 patients underwent surgery after first-line-chemotherapy. The remaining received second- or third-line-chemotherapy prior to surgery. In 12 of 31 evaluable patients, a durable CR was achieved. The median follow-up for this group is 30 months (2-58 months). The histopathologic examination of the resected specimen and the tumor marker level prior to RTR do not permit determination of prognostic outcome. After operation 44% of the AFP-positive and 30% of the beta-HCG-positive patients had a durable remission. If tumor marker levels at time of RTR are within normal range, disease-free survival is 72%; in case of elevated markers 39% will survive. If intensive chemotherapy fails to normalize markers, RTR remains the only option to change the fatal course of the disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

[An interdisciplinary consensus conference on the diagnosis and therapy of testicular tumors].

In 1988 the German testicular working group was set up by leading experts in the fields of urology, medical and radio-oncology. Since then, the working group has initiated several clinical studies and conferences with the aim of defining current standards in the treatment of testicular germ cell tumours. After a series of preliminary joint meetings with representatives from the AUO, AIO and ARO of the "Deutsche Krebsgesellschaft", a conference was held in May 1996 to agree on a consensus in diagnosis and treatment of testicular germ cell tumours. The standards which have been agreed on at the conference refer to the current international literature and provide recommendations for the majority of clinical situations. Treatment strategies differing from these standards should not be chosen except for well argued individual settings or patients treated in clinical trials. No consensus could be reached for nonseminomatous stage I, IIA and IIB tumours. As a consequence, the differing treatment strategies for these stages are summarized in this paper. A subsequent conference in later years is needed to possibly find an agreement for these tumour stages and to update the current standards according to new clinical experience and knowledge.

Combined Modality Therapy↗
PubMed1997

[High-dose chemotherapy and reinfusion of hematopoietic stem cells in advanced germ cells tumors with poor prognosis--the position in 1996].

High-dose chemotherapy (HDCT) is a promising treatment for patients with germ cell tumours and a poor prognosis. The selection of patients who may profit from this intervention is challenging for the urologist, as the indication has to be carefully established. Exclusion criteria primarily concern impaired organ functions. Prior to HDCT haematopoietic stem cells are obtained after the administration of conventional-dose chemotherapy plus G- or GM-CSF stimulation. HDCT consists of a combination of carboplatin, etoposide and ifosfamide or cyclophosphamide. After HDCT, haematologic monitoring and maximal supportive care are essential. It is therefore recommended that HDCT only be administered at specialized centres.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Elevated human chorionic gonadotropin concentrations in the testicular vein and in peripheral venous blood in seminoma patients. An analysis of various parameters.

OBJECTIVE: Human chorionic gonadotropin (HCG) elevations in the testicular vein (TV) are correlated with those in the cubital vein (CV). Their significance was tested regarding various prognostic parameters. METHOD: Within the framework of a large multicentre study to assess the prognosis of HCG-positive seminomas 726 eligible patients were recruited from 1986 to 1991. A total of 378 had elevated and 348 had normal HCG measured in the CV. In 144 patients samples were taken from the TV. Histological diagnosis of seminoma was confirmed by two reference pathologists. Three groups (group I: elevated HCG in CV and normal or elevated HCG in TV; group II: normal HCG in CV and elevated HCG in TV; group III: normal HCG in CV and normal or unknown HCG in TV) were compared in relation to the presence or absence of metastases, stage of the disease, size of the primary tumour, pT category, vascular invasion and lactate dehydrogenase. RESULTS: Of the TV serum samples, 85% were HCG-positive. Regression analysis revealed higher values in the TV compared to the CV according to the following equation: HCGTV = 520 + 1.12 x HCGCV, R = 0.766, with a mean variation of 14%. Patients in group I had significantly higher stages and larger primary tumours than patients with normal HCG in the CV, irrespective of the HCG values in the TV blood (groups II and III). Therefore, HCG is associated with tumour mass. No differences of statistical significance were found regarding T category, vascular invasion and lactate dehydrogenase. There were no differences between groups II and III. CONCLUSION: Only HCG values of the CV are associated with known adverse-prognostic factors of seminomas, such as metastases and size of the tumour. HCG in the TV adds no further information for the clinical assessment of patients with seminoma.

Austria↗
PubMed1997

The value of tumor markers in testicular seminomas. Results of a prospective multicenter study.

OBJECTIVES: In the course of a prospective multicenter trial, the value of tumor markers in seminomas was assessed. METHODS: Human chorionic gonadotropin (HCG), lactate dehydrogenase (LDH) and placental alkaline phosphatase (PlAP) were determined before and after orchidectomy and in the follow-up. Patients with elevated alpha-fetoprotein were considered to have nonseminomas. The half-lives were 24-36 h for HCG and 1 day for LDH and PlAP. RESULTS: The incidence of HCG, LDH and PlAP was 35, 34 and 56%, respectively. In 84% of the patients at least one of the three markers was elevated. PlAP had the highest sensitivity to detect metastatic disease (51%), with a specificity of 91%. HCG and LDH were elevated in 42 and 46% of patients in stage II-III with specificities of 95 and 96%. PlAP was the best method to indicate a relapse, but the specificity was low, especially in smokers. For nonsmokers it was in the same range as HCG and LDH. CONCLUSIONS: Eighty-four percent of seminomas are marker-positive. PlAP has the highest incidence and sensitivity. Specificity is impaired in smokers. All three markers should be determined in seminomas.

Alkaline Phosphatase↗
PubMed1996

Gemcitabine: a phase II study in patients with advanced renal cancer.

Gemcitabine is a fluorine-substituted cytarabine analog with broad experimental antitumor activity. It's activity was explored in chemotherapy-naive patients with advanced progressive renal-cell carcinoma. A total of 39 patients were included in the study, of whom 37 were fully evaluable. In five patients the primary tumor remained in situ. Gemcitabine at 800 mg/m2 was given as a weekly 30-min infusion for 3 consecutive weeks followed by 1 week of rest. One complete response and two partial responses were observed giving a response rate of 8.1% [95% confidence interval (CI), 2-22%]. The duration of the responses is currently 32, 15, and 19 months, respectively. The median survival for all patients was 12.3 months. Gemacitabine was generally well tolerated, with nausea and vomiting (20.5% grade III) and neutropenia (5.3% grade III) being the most significant side effects. Gemcitabine given at this dose level and on this schedule has only limited activity in advanced renal-cell carcinoma.

Adult↗
PubMed1996

Phase II study of paclitaxel in patients with relapsed or cisplatin-refractory testicular cancer.

BACKGROUND: Despite generally high cure rates in patients with metastatic testicular cancer, patients with incomplete responses to cisplatin-based first-line therapy or with relapsed disease have an extremely poor prognosis. Paclitaxel represents an antitumor agent with demonstrated activity in cisplatin-sensitive tumors. In addition, responses to paclitaxel have been observed in patients with platin-refractory ovarian cancers. The current phase II trial evaluates the role of paclitaxel in male patients with cisplatin-refractory or relapsed malignant germ cell tumors. PATIENTS AND METHODS: Twenty-four patients with relapsed, mostly cisplatin-refractory metastatic testicular cancer were treated with paclitaxel as three-hour infusions of 225 mg/m2 at 3-weekly intervals. The patients had received a median of 7 platinum-containing treatment cycles (range 3-12) prior to paclitaxel and 12 patients (50%) had previously received high-dose carboplatin/etoposide-based salvage therapy with autologous stem cell support. RESULTS: Six patients (25%) achieved major responses to paclitaxel with 2 CR (8%) and 4 PR with marker normalisation (17%). In addition, 5 patients (21%) showed disease stabilisation. Median duration of responses to paclitaxel was 8 months (3-16+). Toxicity was tolerable, with mainly granulocytopenia occurring in 50% of patients and peripheral neuropathy > or = grade II in 29%. CONCLUSION: Paclitaxel demonstrates significant antitumor activity in 25% of patients with relapsed or cisplatin-refractory testicular cancer. Combination regimens including paclitaxel may be warranted.

Adolescent↗
PubMed1996

A randomized trial of cisplatin, etoposide and bleomycin (PEB) versus carboplatin, etoposide and bleomycin (CEB) for patients with 'good-risk' metastatic non-seminomatous germ cell tumors.

BACKGROUND: Cisplatin-based combination chemotherapy will cure 70% to 80% of patients with metastatic non-seminomatous germ cell tumors but is associated with the possibility of severe neuro-, oto- and nephro-toxicities. Carboplatin, a cisplatin analogue, is an active drug in testicular cancer with a more favourable spectrum of side effects. In a randomized trial, the German Testicular Cancer Study Group compared a combination regimen of carboplatin, etoposide and bleomycin (CEB) to standard cisplatin, etoposide and bleomycin (PEB) chemotherapy for patients with 'minimal-' and moderate-disease' non-seminomatous germ cell tumors, according to the Indiana University classification. PATIENTS AND METHODS: PEB was given for three cycles at standard doses (given days 1-5), and the CEB regimen consisted of carboplatin (target AUC of 5 mg/ml x min) on day 1, etoposide 120 mg/m2 on days 1 to 3 and bleomycin 30 mg on days 1, 8 and 15. Four cycles of CEB were given, with the omission of bleomycin in the fourth cycle. Thus, the cumulative doses of etoposide and bleomycin applied in the two treatment arms were comparable. Fifty-four patients were entered on the trial, 29 were treated with PEB and 25 with CEB chemotherapy. Patients were stratified according to disease extent (minimal versus moderate) and the degree of tumor marker elevation. Thirty-two patients (59%) belonged to the group with minimal disease and low markers. RESULTS: No significant difference in response to chemotherapy was seen between the two arms, with CR rates of 81% for the PEB arm and 76% for CEB treatment. However, more patients treated with CEB (32% versus 13%) have relapsed after therapy, and 4 patients (16%) have died of disease progression after CEP in contrast to 1 (3%) after PEB therapy. The first interim analysis of negative events (relapse, vital tumor at secondary resection, death from disease and therapy-associated death) showed a significantly higher rate after CEB than after PEB therapy, and the trial was terminated early. After a median follow-up of 33 months for all patients, the calculation of negative events is still significantly in favour of PEB-treated patient, particularly since three late relapses > 2 years have been observed in the CEB arm (P = 0.03). CONCLUSION: This randomized trial demonstrates that even with the use of adequate doses of etoposide and full-dose bleomycin, carboplatin cannot altogether replace cisplatin in patients with testicular cancer. Treatment with the PEB regimen remains the standard approach in patients with 'good-risk' non-seminomatous germ cell tumors.

Adolescent↗
PubMed1996

The Ras GTPase-activating-protein-related human protein IQGAP2 harbors a potential actin binding domain and interacts with calmodulin and Rho family GTPases.

We previously described IQGAP1 as a human protein related to a putative Ras GTPase-activating protein (RasGAP) from the fission yeast Schizosaccharomyces pombe. Here we report the identification of a liver-specific human protein that is 62% identical to IQGAP1. Like IQGAP1, the novel IQGAP2 protein harbors an N-terminal calponin homology motif which functions as an F-actin binding domain in members of the spectrin, filamin, and fimbrin families. Both IQGAPs also harbor several copies of a novel 50- to 55-amino-acid repeat, a single WW domain, and four IQ motifs and have 25% sequence identity with almost the entire S. pombe sar1 RasGAP homolog. As predicted by the presence of IQ motifs, IQGAP2 binds calmodulin. However, neither full-length nor truncated IQGAP2 stimulated the GTPase activity of Ras or its close relatives. Instead, IQGAP2 binds Cdc42 and Racl but not RhoA. This interaction involves the C-terminal half of IQGAP2 and appears to be independent of the nucleotide binding status of the GTPases. Although IQGAP2 shows no GAP activity towards Cdc42 and Rac1, the protein did inhibit both the intrinsic and RhoGAP-stimulated GTP hydrolysis rates of Cdc42 and Rac1, suggesting an alternative mechanism via which IQGAPs might modulate signaling by these GTPases. Since IQGAPs harbor a potential actin binding domain, they could play roles in the Cdc42 and Rac1 controlled generation of specific actin structures.

Actins↗
PubMed1996

[Laparoscopy].

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Diffusion of Innovation↗
PubMed1995

Organ preserving surgery of malignant germ cell tumors.

If a tumor arises in a solitary testis the patient loses fertility and requires lifelong androgen substitution. We describe the technique and results of organ preserving enucleation resection performed in 14 patients. The tumor was excised under (cold) ischemia via a mini-surgical technique using 2-fold magnification and blood vessels were localized intraoperatively by Doppler sonography. The procedure was successful in 10 of 14 patients. In 2 patients the organ required ablation later because of insufficient blood supply. Two patients had subnormal testosterone levels after treatment. There were no local recurrences. Prerequisites for this type of treatment are detailed knowledge of the vascular anatomy of the testis, tumor not too close to the rete testis, largest diameter 20 mm. or less, normal preoperative plasma testosterone level, postoperative local irradiation with 20 Gy., followup biopsies and hormonal status obtained 6 months after enucleation resection, and meticulous followup for early detection of local recurrences or systemic progression.

Adult↗
PubMed1994

Identification of a human rasGAP-related protein containing calmodulin-binding motifs.

Conversion of active GTP-bound Ras to its inactive GDP-bound form is catalyzed by GTPase-activating proteins (GAPs). Two mammalian Ras-specific GAPs, p120GAP and neurofibromin, the product of the NF1 tumor suppressor gene, have been previously described. We report here the identification of a new human cDNA clone, IQGAP1, which predicts a 1657-amino acid protein that displays extensive sequence similarity to the catalytic domain of all previously reported RasGAPs. IQGAP1 is most closely related to the Schizosaccharomyces pombe RasGAP-like protein, Sar1. Sequence similarity to IQGAP1 is seen throughout the entire Sar1 protein. The N-terminal half of IQGAP1, which does not overlap with Sar1, contains six copies of a unique amino acid motif, as well as four so-called IQ motifs. The latter motifs are found in several proteins, including conventional and unconventional myosins, and mediate the interaction with calmodulin and calmodulin-related proteins. Thus, IQGAP1 appears to represent a novel RasGAP-like protein that may link Ras signaling to some calmodulin-mediated process.

Amino Acid Sequence↗
PubMed1994

Size and status of metastases after inductive chemotherapy of germ-cell tumors. Indication for salvage operation.

Secondary resection of metastases remaining after inductive chemotherapy of advanced germ-cell tumors has thus far been obligatory. The absence of malignant components in one-third of all residual tumors and the high risk of the operation have led several authors to reconsider the criteria for this approach. In a retrospective study of 153 cases (127 evaluable) we investigated the histology of the primary tumor and the size of the residual tumor with regard to residual histology and outcome. Patients were divided into the following three groups according to the histology of the primary tumor: group I, pure seminoma (16 patients); group II, nonseminoma without teratoma (32 patients); and group III, nonseminoma with teratoma (79 patients). Among the 16 purely seminomatous tumors, the residual masses ranged from 2 to 12 cm; 12 consisted of necrotic tissue only, 3 contained malignant germ-cell elements, and 1 contained adult teratoma. The residuals of primarily teratoma-free nonseminomas measured 2-16 cm; the smallest residual tumor containing active malignant elements measured 4 cm, and the diameter of the largest necrotic residue was 6 cm. Four residuals contained mature teratoma. The size of residuals from teratomatous primary tumors was 3-24 cm; the smallest malignant tumor measured 5 cm, and the diameter of the largest purely necrotic mass was 8 cm. According to our results, a secondary operation may be omitted if the residual mass of a primary seminoma is smaller than 5 cm or if that of a primary nonseminoma without teratoma is less than 3 cm in diameter.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗