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Biomedical subjects

W Hoffmann

Publications and source records attributed to W Hoffmann.

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

13-cis retinoic acid in combination with interferon-alpha enhances radiation sensitivity of human squamous cell carcinoma cells of the oral cavity.

BACKGROUND: Preclinical and clinical trials demonstrated the antiproliferative and chemopreventive potential of 13-cis retinoic acid in combination with interferon-alpha. The present study was designed to determine the radiosensitizing potential of both drugs after single and combined treatment of human squamous-cell carcinoma cells of the oral cavity in vitro. MATERIAL AND METHODS: The study was performed using the human squamous-cell carcinoma cell line SCC4, which was originally established from a tumor of the oral cavity. Based on clonogenic assays, the inhibition of clonogenic activity and radiosensitizing potential of 13-cis retinoic acid and interferon-alpha after single or combined treatment without and with subsequent irradiation was determined. RESULTS: 13-cis retinoic acid (10 microM) and interferon-alpha (50 IU/ml) showed significant inhibition of clonogenic activity after single treatment. A combined treatment protocol resulted at least in a highly significant additive inhibition of clonogenicity. Treatment with both drugs (5 microM 13-cis retinoic acid, 25 IU/ml IFN-alpha) prior and post irradiation of the cells resulted in a pronounced enhancement of radiation toxicity resulting in significantly decreased SF2- and alpha-values. Combined treatment with both drugs was significantly more effective than single drug treatment. CONCLUSIONS: The data presented indicate that pre- and post-irradiation treatment with 13-cis retinoic acid and interferon-alpha significantly enhance the radiosensitivity of human squamous-cell carcinoma cells, SCC4, in vitro. Therefore, they support the initiation of clinical trials to test the radio-oncological value of such a treatment regime for squamous-cell carcinomas.

Antineoplastic Agents↗
PubMed1999

Chemotherapy in the treatment of recurrent glioblastoma multiforme: ifosfamide versus temozolomide.

PURPOSE: Despite the progress made in neurosurgery and radiotherapy, the prognosis of glioblastoma multiforme (GB) is poor, due to the lack of an effective salvage therapy. In vitro analysis revealed activity for ifosfamide and temozolomide. The usefulness of these agents in recurrent disease was investigated. METHODS: Six adult patients with recurrent GB received one to four courses of 1,500 mg/m2 ifosfamide given over 5 days intravenously. Furthermore, temozolomide (100-200 mg/m2) was given orally over 5 days to 14 patients. RESULTS: After ifosfamide treatment, one partial response and two cases of stable disease were observed. The median survival time was 24 weeks (range of 9-52 weeks). Toxicity analysis revealed one paranoid reaction, three grade III leukocytopenia, and one grade I-II nausea, anemia, and hematuria. Temozolomide therapy resulted in three partial responses and four cases of stable disease. The median survival time (Kaplan-Meier) was 21 weeks (range 4-64 weeks). The major toxicities were grade I-II nausea and hematological side effects (one case of grade IV leuko- and thrombocytopenia). CONCLUSIONS: Ifosfamide treatment might be a feasible approach, but it necessitates hospitalization. Temozolomide showed promising results. Due to its oral application, the patient's quality of life (time out of hospital) is favorable. Subgroups with improved survival were observed.

Adult↗
PubMed1999

Localization of TFF3 peptide to porcine conjunctival goblet cells.

TFF-peptides (formerly P-domain peptides, trefoil factors) form a new family of mucin-associated peptides mainly in the gastrointestinal tract. TFF3 is a typical secretory product of intestinal goblet cells and occurs also in the respiratory tract. Here, polyclonal antisera specific for TFF3 were used in Western blot analysis and immunofluorescence to determine the presence and distribution of TFF3 in the porcine conjunctiva, which is the primary source for ocular mucins. Significant accumulation of TFF3 was detected in conjunctival goblet cells but not in the lacrimal glands. This peptide, together with ocular mucins, may play a role in the rheological function of the tear film.

Animals↗
PubMed1999

Secretion of TFF-peptides by human salivary glands.

TFF-peptides (formerly P-domain peptides, trefoil factors) are typical secretory products of mucin-producing cells and seem to influence the rheological properties of mucous gels. Here, localization studies of TFF-peptides in human salivary glands are presented. Expression studies (polymerase chain reaction) revealed mainly TFF3 transcripts in submandibular and sublingual glands and trace amounts in parotid glands. Only low levels of expression of TFF1 could be monitored in submandibular and sublingual glands, and TFF2 transcripts were hardly detectable in all three major salivary glands. This result was partly confirmed by Western blot analysis, which only detected TFF3 in submandibular glands, but not in sublingual and parotid glands. TFF3 was also shown to be a constituent of human saliva. Immunofluorescence localized TFF3 solely in the secretory granules of serous cells of submandibular glands but not in mucous cells. This localization is remarkably similar to that of the unique low-molecular-weight mucin MUC7, which interacts with a number of oral microorganisms.

Blotting, Western↗
PubMed1999

Differential behavioral effects of TFF peptides: injections of synthetic TFF3 into the rat amygdala.

TFF peptides (formerly named P-domain peptides or trefoil factors) are also released from the brain as well as being secreted typically by mucin producing cells. The amygdala, besides the hypothalamus, represents a defined neuronal locality of TFF3 synthesis. In a passive avoidance test synthetic TFF3/monomer or 0.9% sodium chloride (control) was injected bilaterally into the basolateral nucleus of the amygdala of male rats either immediately (consolidation test) or 23 h after a footshock (retrieval test). Application of a low TFF3 dose (2 x 6 pg) decreased avoidance latency in a time dependent manner. In contrast, a high dose (2 x 60 pg) increased avoidance latency. Maximal effects of TFF3 were observed about 24 h after the injection. This bidirectional effect was also observed using the elevated plus-maze test. The locomotor activity on the open arms was significantly increased 24 h after a low dose injection of TFF3 into the amygdala. In contrast, a high-dose injection significantly decreased the activity on the open arms. The results of both tests can be explained by an anxiolytic effect at a low dose and an anxiogenic effect at a high dose of synthetic TFF3/monomer.

Amygdala↗
PubMed1999

Induction of TFF1 gene expression in pancreas overexpressing transforming growth factor alpha.

BACKGROUND/AIMS: Chronic pancreatitis is an inflammatory disease of the exocrine pancreas associated with extensive fibrosis, enlarged pancreatic ducts, acinar cell degeneration, and the formation of tubular complexes. The molecular and biochemical alterations associated with these histological changes are not kown. Generally, the new family of TFF peptides (formerly known as P-domain peptides or trefoil factors) is aberrantly expressed during chronic inflammatory diseases of the gastrointestinal tract. METHODS: Using human pancreatic tissues obtained from patients with chronic pancreatitis and murine pancreatic tissues obtained from transgenic mice overexpressing transforming growth factor alpha (TGF-alpha), the expression and cellular distribution of TFF1 was analysed using northern blot analysis, polymerase chain reaction (PCR), and immunohistochemistry. RESULTS: In the normal human pancreas, TFF1 was scarce, with only a few ducts exhibiting cytoplasmic TFF1 immunoreactivity. In contrast, human chronic pancreatitis tissue specimens exhibited strong TFF1 immunoreactivity in ductal cells, areas of ductal hyperplasia, and tubular complexes. Semiquantitative PCR analysis of TFF1 mRNA levels showed enhanced expression of TFF1 in the pancreas of patients with chronic pancreatitis. Furthermore, TFF1 mRNA levels were detectable in the pancreas in four of five transgenic mice overexpressing TGF-alpha. In contrast, four of five wild type mice did not exhibit a TFF1 mRNA transcript. In addition, while no specific TFF1 immunoreactivity was present in the pancreas of the wild type mice, ductal epithelial cells and duct-like tubular complexes in the pancreas of the transgenic mice overexpressing TGF-alpha exhibited pronounced TFF1 immunoreactivity. CONCLUSIONS: Ductal cells and tubular complexes in pancreatic fibrosis express TFF1. As the 5'-flanking region of TFF1 contains an epidermal growth factor responsive enhancer region and the expression of epidermal growth factor and TGF-alpha is enhanced in pancreatic fibrosis, the enhanced expression of TFF1 in pancreatic fibrosis may be mediated by TGF-alpha.

Adolescent↗
PubMed1999

Localization of TFF3, a new mucus-associated peptide of the human respiratory tract.

Trefoil factor family (TFF)-domain peptides (formerly P-domain peptides, trefoil factors) represent major mucin-associated peptides of the gastrointestinal tract. Here, the first localization studies on TFF3 in the lower respiratory tract of human material are presented. Immunohistochemistry revealed significant accumulation of TFF3 to mucous cells in the acini of submucosal glands and varying amounts in goblet cells at the ductular portions and the surface epithelium. TFF3 appears also as a component of the mucus, for example from patients with chronic bronchitis. Expression of TFF3 was also shown by use of the polymerase chain reaction. In contrast, TFF1 and TFF2 transcripts were hardly detectable in the human respiratory tract. Thus, a structural function of TFF3 for the airway mucus is discussed, possibly together with the mucins MUC5B and MUC5AC.

Blotting, Western↗
PubMed1999

UFT plus calcium folinate plus radiotherapy for recurrent rectal cancer.

Uracil and tegafur (in a molar ratio of 4:1 [UFT]) plus calcium folinate comprise the components of the oral agent, Orzel, which appears to have activity comparable to intravenously administered 5-fluorouracil. This article describes the design of an open-label, disease-oriented, phase I trial of UFT plus calcium folinate in combination with simultaneous pelvic radiation for recurrent rectal cancer. This trial is designed to determine the maximum tolerated dose and dose-limiting toxicity of this regimen.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1999

Secretory peptides TFF1 and TFF3 synthesized in human conjunctival goblet cells.

PURPOSE: The objective of this study was to determine whether human conjunctival epithelium synthesizes TFF-peptides (formerly P-domain peptides, trefoil factors), a family of mucin-associated secretory peptides of the gastrointestinal tract. METHODS: Expression of TFF-peptides in human conjunctiva was monitored by reverse transcription-polymerase chain reaction analysis. Antisera specific for TFF-peptides were used for immunohistochemistry to determine the presence and distribution of TFF-peptides in human conjunctiva. RESULTS: mRNA expression of TFF1 and TFF3, but not TFF2, was detected in human conjunctiva. TFF1 and TFF3 but not TFF2 are stored in conjunctival goblet cells only as revealed by immunofluorescence. CONCLUSIONS: Goblet cells of the human conjunctiva synthesize TFF1 and TFF3. These peptides, together with the secretory ocular mucin MUC5AC, may contribute to the rheological properties of the tear film. They also may influence healing of corneal wounds due to their motogenic properties.

Aged↗
PubMed1999

[Effects of priming technique on onset profile of cisatracurium].

Compared to atracurium, cisatracurium releases less laudanosine and histamine, but it has a longer onset time. The primary objective of this study was a blinded, randomized comparison of intubation scores and onset times of a threefold ED 95 of cisatracurium using the priming technique with two priming substances cisatracurium itself and pancuronium. To test the effect of priming with cisatracurium or pancuronium on the onset of cisatracurium, 45 patients were anaesthetised with 0.15-0.25 mg/kg alfentanil, 0.25-0.3 mg/kg edomidate i.v. and O2/N2O, and were randomisely divided into one of three groups. After induction, 15 patients were primed with sodium chloride and thereafter received 0.15 mg/kg cisatracurium, 15 patients were primed with 0.01 mg/kg cisatracurium, another 15 patients were primed with 0.015 mg/kg pancuronium and the last two groups received 0.14 mg/kg cisatracurium three minutes later. Neuromuscular response was monitored by adductor pollicis electromyogram (EMG) by stimulating in a TOF pattern. Times for T1 reduction to 75%, 50%, 25% and 0% and T1 recovery to 25% were taken. Intubation was performed 120 seconds after the main relaxant dose and scored in four grades. The two priming groups showed a significantly faster onset of neuromuscular blockade than the control group (cisatracurium priming group: T1 = 0: 178.4 +/- 16.3 sec., pancuronium priming group 171.2 +/- 15.3 sec. vs. control group: T1 = 0: 205.5 +/- 18.9 sec.). Both primed groups showed no significantly better intubation scores, compared with the control group. Using the priming principle, cisatracurium will give good intubation scores 120 seconds after injection with a clinical duration profile comparable to an equipotent dose of atracurium.

Adult↗
PubMed1998

Differential expression of the TFF-peptides xP1 and xP4 in the gastrointestinal tract of Xenopus laevis.

TFF-peptides (formerly P-domain peptides, trefoil factors) represent major secretory products of the mammalian gastrointestinal tract. A molecular cloning approach revealed the existence of two TFF-peptides, xP1 and xP4, also in the stomach of Xenopus laevis. Here, the localization of these two peptides by Western blot analysis as well as immunohistochemistry is presented. xP1 is found predominantly in the surface mucous cells of the stomach, whereas xP4 is mainly localized to a specific population of goblet cells in the esophagus, to mucous neck cells of the stomach, and to closely resembling cells in antral glands. xP4 in the esophagus and in the stomach differ by their N-glycosylation patterns. Compared to mammalian TFF-peptides, xP1 obviously represents the frog homologue of human TFF1 (formerly pS2) and xP4 seems to be the amphibian equivalent of human TFF2 (formerly hSP).

Animals↗
PubMed1998

Permanent junctional re-entry tachycardia. A multicentre long-term follow-up study in infants, children and young adults.

AIMS: Permanent junctional re-entry tachycardia is a relatively uncommon form of re-entry tachycardia with antegrade conduction occurring through the atrioventricular node and retrograde conduction over an accessory pathway usually located in the postero-septal region. It was the aim of the study to investigate the course of permanent junctional re-entry tachycardia with particular regard to the effectiveness of pharmacological treatment and ablation procedures; evaluation was performed with respect to the patient's symptoms, tachycardia rate, frequency of the tachycardia and left ventricular function. METHODS AND RESULTS: The long-term follow-up of 32 patients with permanent junctional re-entry tachycardia was evaluated. The first presentation with supraventricular tachycardia occurred between the 27th week of gestation and 27 years. The tachycardia rate ranged from 100 to 250 beats.min-1. During Holter-ECG, permanent junctional re-entry tachycardia was documented as present for over 50% of the time in 24 h in 22 patients (69%). Left ventricular performance was impaired in nine patients (28%) due to a tachycardia-related cardiomyopathy. Symptoms or signs of heart failure were mild to moderate in eight and severe in four patients; 20 patients showed no clinical impairment. Follow-up time was 1 to 31 (mean 10) years; current age of the patients ranged from 1.5 months to 35 (mean = 15 x 3) years. Four patients needed no therapy because of the infrequency of permanent junctional re-entry tachycardia episodes. Twenty-five patients initially received antiarrhythmic drugs, which were effective or partially effective in 14 (56%). Eight of them are still on medical therapy; in five treatment was discontinued because of absence of symptoms. Eleven patients had ablation of the accessory pathway during follow-up, three underwent ablation as a primary procedure. CONCLUSION: Permanent junctional re-entry tachycardia in our experience is an arrhythmia with a large variety of clinical symptoms. Patients with a slow tachycardia rate and infrequent episodes of tachycardia may never develop symptoms and therefore do not need any therapy. Patients with frequent permanent junctional re-entry tachycardia, a fast tachycardia rate and impaired left ventricular function need effective therapy. In infancy and early childhood medical therapy is recommended as a first option, whereas in older and symptomatic patients catheter ablation is an effective and safe procedure.

Adolescent↗
PubMed1998

Mitomycin C-related hemolytic uremic syndrome in cancer patients.

In rare cases mitomycin C (MMC) may induce cancer-associated hemolytic uremic syndrome, which is characterized by hemolytic anemia, thrombocytopenia and progressive renal failure. Treatment possibilities of this multisystem disease up to now remain disappointing. We report a case of MMC-related hemolytic uremic syndrome, and discuss the etiologic parameters, clinical aspects, prognosis and treatment modalities of this severe syndrome.

Adenocarcinoma↗
PubMed1998

Letrozole, a new oral aromatase inhibitor for advanced breast cancer: double-blind randomized trial showing a dose effect and improved efficacy and tolerability compared with megestrol acetate.

PURPOSE: To compare two doses of letrozole and megestrol acetate (MA) as second-line therapy in postmenopausal women with advanced breast cancer previously treated with antiestrogens. PATIENTS AND METHODS: Five hundred fifty-one patients with locally advanced, locoregionally recurrent or metastatic breast cancer were randomly assigned to receive letrozole 2.5 mg (n = 174), letrozole 0.5 mg (n = 188), or MA 160 mg (n = 189) once daily in a double-blind, multicenter trial. Data were analyzed for tumor response and safety variables up to 33 months of follow-up evaluation and for survival up to 45 months. RESULTS: Letrozole 2.5 mg produced a significantly higher overall objective response rate (24%) compared with MA (16%; logistic regression, P = .04) or letrozole 0.5 mg (13%; P = .004). Duration of objective response was significantly longer for letrozole 2.5 mg compared with MA (Cox regression, P = .02). Letrozole 2.5 mg was significantly superior to MA and letrozole 0.5 mg in time to treatment failure (P = .04 and P = .002, respectively). For time to progression, letrozole 2.5 mg was superior to letrozole 0.5 mg (P = .02), but not to MA (P = .07). There was a significant dose effect in overall survival in favor of letrozole 2.5 mg (P = .03) compared with letrozole 0.5 mg. Letrozole was significantly better tolerated than MA with respect to serious adverse experiences, discontinuation due to poor tolerability, cardiovascular side effects, and weight gain. CONCLUSION: The data show letrozole 2.5 mg once daily to be more effective and better tolerated than MA in the treatment of postmenopausal women with advanced breast cancer previously treated with antiestrogens.

Administration, Oral↗