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H Huber

Publications and source records attributed to H Huber.

At least 73 records · Page 4Linked to original sources
PubMed1999

[Fundamentals and results of cytostatic chemotherapy in some of the most common solid tumors].

In this review we discuss established cytostatic chemotherapies as well as developments and perspectives for the three most common tumour entities. Adjuvant and neoadjuvant therapy models for primary breast cancer are discussed, established and newer concepts in palliative care presented and open questions about high dose chemotherapy raised, which need to be settled before their routine use. Developments in the field of lung cancer therapy such as adjuvant and neoadjuvant approaches are pointed out and the importance of multimodal and interdisciplinary treatment modalities is underlined. Newer cytostatic drugs are compared with established agents. In the field of colorectal cancer several new thymidilatsynthase-inhibitors as well as drugs with different mode of action are available. With these new agents, [table: see text] cytostatic therapy of advanced stages and most probably also in the adjuvant setting could markedly be improved.

Antineoplastic Agents↗
PubMed1999

Adjuvant and induction chemotherapy in non-small cell lung cancer.

About 25%-30% of patients with non-small cell lung cancer can be resected with curative intent. However, systemic relapses occur in up to 70% of these patients. Thus, postoperative adjuvant chemotherapy was evaluated in several randomised trials but the results of these trials were inconclusive with a survival benefit only in some trials. Shortcomings of these trials included low number of patients, poor patient compliance and inadequate chemotherapy protocols. A recent meta-analysis suggested an absolute survival benefit of 5% at five years for postoperative cisplatin-based chemotherapy as compared to surgery alone. Thus adjuvant chemotherapy with both improved chemotherapy protocols and improved anti-emetics is currently re-evaluated in several randomised trials on large patient populations.

Antineoplastic Agents↗
PubMed1998

Retinoids control the expression of c-erbB receptors in breast cancer cells.

Nuclear retinoid and membrane c-erbB receptors participate in signal transduction systems that control mammary epithelial cell proliferation and differentiation. Recently, we demonstrated that c-erbB receptor activation stimulates retinoic acid receptor-alpha expression. We now report that retinoids reduce SK-BR-3 breast cancer cell growth by inhibiting the cell cycle and by inducing apoptosis. This is accompanied with reduced c-erbB expression as determined by FACS, Western, Northern, RT-PCR, and reporter assays. All-trans (ATRA) and 9-cis retinoic acid (9cRA) reduce c-erbB-1 protein to 50-100%, c-erbB-2 to 20-30%, and c-erbB-3 to 10-50% of control, depending on the concentration, respectively, without influencing the tyrosine phosphorylation status. Down-regulation of c-erbB-2 and -3 was seen at all levels analyzed, whereas c-erbB-1 mRNA remained unchanged. Retinoic acid-mediated down-regulation of growth and c-erbB-2 and -3 expression was also seen in MCF-7 cells. We conclude that retinoic acids are efficient repressors of c-erbB-2 and -3 gene expression, whereas c-erbB-1 is not markedly affected.

Alitretinoin↗
PubMed1998

Evidence for a novel type of iron cluster in the respiratory chain of the archaeon Sulfolobus metallicus.

A new type of metal centre was detected in the membranes of the thermoacidophilic archaeon Sulfolobus metallicus. This centre has an S = 1/2 ground state in the oxidised form, yielding an axial EPR signal with g values at 2.035 (g(parallel)) and 1.97 (g(perpendicular)), optimally detected at 4.6-10 K; in the reduced form it is EPR silent (even spin). These magnetic properties point to a spin-coupled iron cluster, with a minimum of two iron ions. The centre has a high reduction potential of +350 mV, at pH 6.5. The physiological role of this novel centre was probed through a general characterisation of S. metallicus respiratory chain: this archaeon contains NADH and succinate dehydrogenase activities, and cytochromes b562, a586 and a600 on the oxygen reductase system. Since it is reduced in the presence of succinate, and taking into account its high reduction potential, this centre is proposed to be a functional analogue of the Rieske centres.

Animals↗
PubMed1998

Presence of a p53 gene deletion in patients with multiple myeloma predicts for short survival after conventional-dose chemotherapy.

In multiple myeloma (MM), previous studies showed that mutations of the p53 gene are rare events in patients with newly diagnosed disease, but it is not known whether deletions of p53 are of any significance in MM. To address this question, we used interphase fluorescence in situ hybridization (FISH) with a DNA probe specific for the p53 locus at 17p13 and investigated bone marrow plasma cells from 72 patients with MM (59 patients = 81.9% before therapy). By FISH, deletions of p53, which were found to be predominantly monoallelic, were detected in 32.8% and 54.5% of patients with newly diagnosed and relapsed MM, respectively. Karyotypes from six of the patients with a p53 deletion by FISH showed a structural abnormality of 17p in only one of them. Additional FISH studies including a distal-17p probe (specific for the D17S34 locus) provided evidence for an interstitial deletion on 17p resulting in loss of p53 hybridization signals in myeloma cells. Among all 59 patients with newly diagnosed MM, presence of a p53 deletion was associated with stage III (P = .054), but not with other laboratory and clinical parameters. Patients with a p53 deletion had significantly shorter survival time compared with those without a deletion, both from the time of diagnosis (median 13.9 v 38.7 months; P < .0001) and from the time of initiation of induction treatment consisting of conventional dose chemotherapy (median 15.9 months v median not reached at 38 months; P < .0002). On stepwise multivariate regression analysis, presence of a p53 deletion was the most significant independent parameter predicting for shortened survival (P = .002). We conclude that a p53 gene deletion, which can be identified by interphase FISH in almost a third of patients with newly diagnosed MM, is a novel prognostic factor predicting for short survival of MM patients treated with conventional-dose chemotherapy.

Adult↗
PubMed1998

Crystal structure of the thermosome, the archaeal chaperonin and homolog of CCT.

We have determined to 2.6 A resolution the crystal structure of the thermosome, the archaeal group II chaperonin from T. acidophilum. The hexadecameric homolog of the eukaryotic chaperonin CCT/TRiC shows an (alphabeta)4(alphabeta)4 subunit assembly. Domain folds are homologous to GroEL but form a novel type of inter-ring contact. The domain arrangement resembles the GroEL-GroES cis-ring. Parts of the apical domains form a lid creating a closed conformation. The lid substitutes for a GroES-like cochaperonin that is absent in the CCT/TRiC system. The central cavity has a polar surface implicated in protein folding. Binding of the transition state analog Mg-ADP-AIF3 suggests that the closed conformation corresponds to the ATP form.

Adenosine Diphosphate↗
PubMed1998

Purification and properties of an extremely thermostable membrane-bound sulfur-reducing complex from the hyperthermophilic Pyrodictium abyssi.

The chemolithoautotrophic archaeon Pyrodictium abyssi isolate TAG 11 gains energy by reducing sulfur with H2 to H2S. From this hyperthermophile, a sulfur-reducing complex catalyzing this reaction was purified 13.5-fold. The native complex exhibited a brownish-yellow colour and showed an apparent molecular mass of 520 kDa. SDS/PAGE revealed the presence of nine different major polypeptides with apparent molecular masses of 82, 72, 65, 50, 47, 42, 40, 30 and 24 kDa. The native complex contained 50-55 mol acid-labile sulfur, 50-55 mol iron, 1.6 mol nickel, 1.2 mol copper, 2.8 mol cytochrome b and 0.3 mol cytochrome c (all per mol native complex). The temperature optimum of the H2:sulfur oxidoreductase complex was 100 degrees C, which is consistent with the physiological growth optimum of the native organism. The complex is extremely heat stable. During 5 h incubation at 100 degrees C, no decrease in H2S-forming activity could be observed.

Amino Acid Sequence↗
PubMed1998

Relation between occupational asthma case history, bronchial methacholine challenge, and specific challenge test in patients with suspected occupational asthma.

Inhalative methacholine challenge (MC) was performed in 229 subjects presumed to suffer from occupational asthma due to exposure to airborne latex allergens (n = 62), flour (n = 28), isocyanates (n = 114), or irritants in hairdressers' salons (n = 25). They were also subjected to specific challenges with the occupational agents they were exposed to, completed a questionnaire using an abbreviated version of the ATS-DLD, and were interviewed by an experienced physician. Bronchial hyperresponsiveness in MC was defined by the results obtained in a previous study with 81 healthy volunteers. The threshold in these controls was set at a cumulative MC dose of 0.3 mg, corresponding to a sensitivity of 95%. The main purpose of the study was to investigate whether the MC and/or the occupational asthma case history are reliable predictors of the specific challenge test outcomes. In 40-72% of examined subjects, workplace-related asthma complaints occurred, with bronchial hyperreactivity in the MC ranging from 48% to 61%. However, only 12-25% demonstrated a significant bronchoconstructive reaction in the specific challenge test. MC results are only moderately associated with workplace-related asthma case histories. Positive outcomes of challenges with occupational agents are well correlated with positive MC results plus occupational asthma case histories. The combination of MC and occupational asthma case history shows a relatively high specificity (62%, 86%, 80%), but the sensitivity was moderately low (83%, 71%, 52%). MC sensitivities were 92%, 71%, and 62% (case histories of hairdressers were not available). We conclude that in most cases, occupational asthma (as defined by a specific challenge test response) is combined with bronchial hyperresponsiveness and workplace-related asthmatic symptoms. However, subjects of each exposure group demonstrated bronchial hyperresponsiveness and complained of workplace-related asthmatic symptoms, but occupational asthma could not be proved in the specific challenge test. In subjects with a positive occupational asthma case history, a negative MC test result can almost rule out a positive specific challenges test result. Hence, the MC test can reduce performance of the laborious specific challenge test.

Adult↗
PubMed1998

Estimation of genome sizes of hyperthermophiles.

Genomes of various hyperthermophilic and extremely thermophilic prokaryotes were analyzed with respect to size, physical organization, and 16S rDNA copy number. Our results show that all the genomes are circular, and they are in the size range of 1.6-1.8 Mb for Pyrodictium abyssi, Methanococcus igneus, Pyrobaculum aerophilum, Archaeoglobus fulgidus, Archaeoglobus lithotrophicus, and Archaeoglobus profundus (the two bacteria Fervidobacterium islandicum and Thermosipho africanus possess genomes of 1.5-Mb size). A systematic study of all validly described species of the order Sulfolobales revealed the existence of two classes of genome size for these archaea, correlating with phylogenetic analyses. The Metallosphaera-Acidianus group, plus Sulfolobus metallicus, have genomes of ca. 1.9 Mb; the other members of the order Sulfolobales group possess genome > 2.7 Mb. The special case of stygiolobus azoricus is discussed.

Archaea↗
PubMed1998

Vinorelbine/gemcitabine in advanced non-small cell lung cancer (NSCLC): a phase I trial.

Vinorelbine and gemcitabine are both active as single agents in advanced non-small cell lung cancer (NSCLC). Because of their different mechanisms of action, good tolerability and possible administration on an out-patient basis, vinorelbine/gemcitabine should be an interesting combination for palliative chemotherapy. Thus, we initiated a phase I dose-escalation trial in order to determine the maximum tolerated doses of vinorelbine/gemcitabine that can be administered without haematopoietic growth factors, the dose-limiting toxicities and the most frequent side-effects of this novel combination. 40 chemotherapy-naïve patients with advanced NSCLC were treated with different doses of vinorelbine/gemcitabine on days 1, 8 and 15, and this treatment cycle was repeated on day 29. Vinorelbine and gemcitabine were escalated from 10 to 30 mg/m2 and 600 to 1200 mg/m2, respectively. A total of 63 treatment cycles were administered and 27 patients received at least two treatment cycles. Dose-limiting toxicities were leucopenia plus thrombocytopenia (2 patients) and mucositis (1 patient). The maximum tolerated dose was established at 25 mg/m2 vinorelbine combined with 1200 mg/m2 gemcitabine. Frequent side-effects were leucopenia, anaemia, nausea/vomiting, flu-like symptoms, skin rashes and elevation of liver enzymes. The recommended phase II doses are 20-25 mg/m2 vinorelbine combined with 1000-1200 mg/m2 gemcitabine on days 1, 8 and 15, but myelosuppression will have to be carefully monitored.

Adult↗
PubMed1998

Aneuploidy of chromosome 8 as detected by interphase fluorescence in situ hybridization is a recurrent finding in primary and metastatic breast cancer.

Previous work from our laboratory demonstrated aneuploidy for several chromosomes by interphase fluorescence in situ hybridization (FISH) in a high proportion of breast cancer specimens. In the literature, only limited data are available concerning chromosome 8 anomalies in breast cancer. To determine chromosome 8 ploidy status in primary and metastatic specimens from 81 breast cancer patients, FISH analysis with a DNA probe recognizing chromosome 8 centromeres was performed. In all primary tumor specimens (n = 30), significant proportions of cells were aneuploid exhibiting gain of chromosome 8 copy numbers; in 75% of effusion specimens previously classified as malignant by cytology and/or FISH for various chromosomes (n = 40), cell populations aneuploid for chromosome 8 were detected; effusions previously classified non-malignant (n = 11) were diploid in 10 cases, whereas one specimen contained rare hyperdiploid cells. Among these cells complex chromosomal aneuploidy could be demonstrated by two-color FISH, suggesting malignancy. Trisomic and tetrasomic clones were predominant in the majority of samples, but a marked intratumor cytogenetic heterogeneity was observed in most cases. Primary tumors and corresponding positive axillary lymph nodes revealed similar distributions of chromosome 8 copy numbers, analogous to previous findings with other chromosomes. This implies that, by using suitable FISH probes after examination of the respective primary tumor, an efficient search for (micro)metastasis might be feasible.

Adult↗
PubMed1998

Chromosomal imbalances in primary and metastatic pancreatic carcinoma as detected by interphase cytogenetics: basic findings and clinical aspects.

To date, cytogenetic studies on pancreatic carcinoma are rare, and little is known about the frequency of cytogenetic aberrations in primary carcinomas compared with metastatic tumour cells. We therefore evaluated the frequency of chromosomal aberrations in 12 primary pancreatic carcinomas and in effusion specimens from 25 patients with pancreatic cancer by using interphase fluorescence in situ hybridization (FISH) and a panel of four centromeric probes. Hyperdiploidy and chromosomal imbalances, predominantly affecting chromosome 8, were a constant finding in metastatic effusion cells, whereas concordant gain of chromosomes or relative loss of chromosome 18 characterized primary pancreatic carcinomas. The potential role of oncogenes located on chromosome 8 for pancreatic cancer progression was further investigated by double-hybridization studies of aneuploid effusion cells with a probe to 8q24 (MYC) and a centromeric probe to chromosome 8, which demonstrated amplification of the MYC oncogene in two of ten cases (20%). Finally, a potential application of basic findings in the clinical setting was tested by searching for micrometastatic cells in effusions from pancreatic cancer patients primarily negative by FISH. Two-colour FISH in combination with extensive screening (>10,000 nuclei) seems to be a useful tool to unequivocally identify micrometastatic cells by demonstrating hyperdiploidy and intranuclear chromosomal heterogeneity.

Ascites↗
PubMed1998

Effects of retinoic acid and fenretinide on the c-erbB-2 expression, growth and cisplatin sensitivity of breast cancer cells.

We investigated the effects of all-trans retinoic acid (ATRA) and fenretinide (4-HPR) on c-erbB-2 expression in SK-BR-3, BT-474 and MCF-7 breast cancer cells and on the growth, differentiation, apoptosis and cisplatin (CDDP) sensitivity of SK-BR-3 cells. It has been reported that oestrogen inhibits c-erbB-2 in oestrogen receptor-positive breast cancer cells. Using ELISA, Western and Northern analysis we have demonstrated that ATRA and 4-HPR exert similar effects down-regulating c-erbB-2 protein and mRNA in c-erbB-2-overexpressing SK-BR-3 and BT-474 and in normally expressing MCF-7 cells. Both retinoids inhibit SK-BR-3 cell growth. ATRA induces cellular enlargement and flattening, suggesting epithelial differentiation. 4-HPR causes nuclear and cytoplasmic condensation, DNA fragmentation and externalization of phosphatidylserine, indicating apoptosis. c-erbB-2 expression/activity has been linked to sensitivity against CDDP. Therefore, combinations of ATRA or 4-HPR with CDDP were tested for their anti-proliferative activity. Retinoid-conditioned cells were either exposed to retinoid and CDDP (schedule I, 'continuous retinoid treatment') or to CDDP alone (schedule II, 'retinoid pretreatment'). This retinoid-conditioning followed by CDDP +/- retinoid yields stronger growth inhibition compared with unconditioned cells, which were exposed to CDDP +/- retinoid (schedule III, 'no retinoid pretreatment'). The inefficacy of schedule III indicates that retinoid-conditioning is essential for the improvement of the antiproliferative effect. The interactions in schedules I and II are synergistic for ATRA and CDDP, but slightly antagonistic for 4-HPR and CDDR However, 4-HPR + CDDP is more effective in growth inhibition than each drug alone.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Absence of p53 deletions in bone marrow plasma cells of patients with monoclonal gammopathy of undetermined significance.

We have recently shown that presence of a p53 deletion in multiple myleoma is an independent predictor for short survival. We therefore investigated whether or not this chromosomal abnormality can be identified in patients with monoclonal gammopathy of undetermined significance (MGUS). Using a triple staining method combining staining for cytoplasmic immunoglobulins and fluorescence in situ hybridization (FISH) with chromosome 17-centromere and p53-gene specific probes, we studied plasma cells from 15 patients with MGUS. In all patients, concordant signal numbers with both probes were obtained (including one patient with trisomy 17), indicating that allelic loss of p53 does not occur in MGUS.

Bone Marrow Cells↗
PubMed1998

Sulfur-inhibited Thermosphaera aggregans sp. nov., a new genus of hyperthermophilic archaea isolated after its prediction from environmentally derived 16S rRNA sequences.

Recently, a new procedure was developed which allowed for the first time the isolation of a hyperthermophilic archaeum tracked by 165 rRNA analysis from a terrestrial hot solfataric spring ('Obsidian Pool', Yellowstone National Park, WY, USA). This novel isolate is characterized here. Cells are round cocci with a diameter of 0.2-0.8 micron, occurring singly, in pairs, short chains and in grape-like aggregates. The aggregates exhibit a weak bluish-green fluorescence under UV radiation at 420 nm. The new isolate is an anaerobic obligate heterotroph, using preferentially yeast extract for growth. The metabolic products include CO2, H2, acetate and isovalerate. Growth is observed between 65 and 90 degrees C (optimum: 85 degrees C), from pH 5.0 to 7.0 (optimum: 6.5) and up to 0.7% NaCl. The apparent activation energy for growth is about 149 kJ mol-1. Elemental sulfur or hydrogen inhibits growth. The core lipids consist mainly of acyclic and cyclic glycerol diphytanyl tetraethers. The cell envelope contains a cytoplasmic membrane covered by an amorphous layer of unknown composition; there is no evidence for a regularly arrayed surface-layer protein. The G + C content is 46 mol%. On the basis of 165 rRNA sequence comparisons in combination with morphological, physiological and biochemical properties, the isolate represents a new genus within the Desulfurococcaceae, which has been named Thermosphaera. The type species is Thermosphaera aggregans, the type strain is isolate M11TLT (= DSM 11486T).

Bacteriological Techniques↗
PubMed1998

Thermocrinis ruber gen. nov., sp. nov., A pink-filament-forming hyperthermophilic bacterium isolated from yellowstone national park

A novel hyperthermophilic bacterium was isolated from pink filamentous streamers (pink filaments) occurring in the upper outflow channel (temperature, 82 to 88 degreesC) of Octopus Spring in Yellowstone National Park, Wyo. The gram-negative cells grew at low salinity at temperatures up to 89 degreesC in the neutral to alkaline pH range. Depending on the culture conditions, the organisms occurred as single motile rods, as aggregates, or as long filaments that formed streamer-like cell masses. The novel isolate grew chemolithoautotrophically with hydrogen, thiosulfate, and elemental sulfur as electron donors and oxygen as the electron acceptor. Alternatively, under aerobic conditions, formate and formamide served as sole energy and carbon sources. The novel isolate had a 16S rRNA sequence closely related to the 16S rRNA sequence obtained from uncultivated pink filaments. It represents a new genus in the order Aquificales, the type species of which we name Thermocrinis ruber (type strain, OC 1/4 [= DSM 12173]).

Journal Article↗
PubMed1998

[Release of the carpal tunnel by endoscopy].

GOALS OF THE STUDY: Review of the results of 67 endoscopic carpal tunnel releases and description of the surgical technique. MATERIAL AND METHODS: Between 1994 and 96, 67 endoscopic carpal tunnel release have been performed on 49 patients with a mean age of 58 years. Our mean follow-up is 13 months. RESULTS: 31 patients (65%) reported an excellent result, 14 patients (28.5%) reported an improvement of their symptoms and 3 patients (6.5%) no improvement at all. The mean time for return to work was 4.5 weeks and 40% return after 3 weeks. DISCUSSION: Endoscopic carpal tunnel release is effective in relieving symptoms and is associated with an early return to work and minimal palmar pain. The endoscopic release has advantages over open release but this technique has her own complications.

Adult↗