Search PubMed⌕ Search

Biomedical subjects

W Jaeger

Publications and source records attributed to W Jaeger.

At least 19 recordsLinked to original sources
PubMed2006

Resveratrol, an ingredient of wine, acts synergistically with Ara-C and tiazofurin in HL-60 human promyelocytic leukemia cells.

Resveratrol (RV), a naturally occurring stilbene derivative, is a potent free radical scavenger causing a number of biochemical and antineoplastic effects. It was shown to induce differentiation and apoptosis in leukemia cells and was also identified as an inhibitor of ribonucleotide reductase (RR), a key enzyme of DNA synthesis. In this study, we report about the biochemical effects of RV in HL-60 human promyelocytic leukemia cells. RV effectively inhibited in situ RR activity. Furthermore, incubation of HL-60 cells with RV significantly decreased intracellular dCTP, dTTP, dATP and dGTP concentrations. In growth inhibition and clonogenic assays, RV acted synergistically with both Ara-C and tiazofurin in HL-60 cells. We conclude that RV could become a viable candidate as one compound in the combination chemotherapy of leukemia and therefore deserves further in vitro and in vivo testing.

Antimetabolites, Antineoplastic↗
PubMed2006

Antitumor effects of 3,3',4,4',5,5'-hexahydroxystilbene in HL-60 human promyelocytic leukemia cells.

Resveratrol (3,4',5-trihydroxystilbene, RV) exerts remarkable cytostatic and cytotoxic effects against a multitude of human cancer cell lines. Since the introduction of additional hydroxyl groups was supposed to increase the biological activity of RV, we have synthesized a number of polyhydroxylated stilbene analogues as potential antitumor agents. In this study, the activity of 3,3',4,4',5,5'-hexahydroxystilbene (M8) was investigated in HL-60 human promyelocytic leukemia cells. Employing a growth inhibition assay, incubation with M8 and RV resulted in IC50 values of 6.25 and 12 microM, respectively. Using a specific Hoechst/propidium iodide double staining method, we found that M8 was able to induce apoptosis in concentrations significantly lower than those of RV. In addition, M8 arrested cells in the S phase and totally depleted cells in the G2-M phase of the cell cycle (143% and 0% of control after treatment with 12.5 microM M8, respectively). We therefore believe that this promising agent deserves further preclinical and in vivo testing.

Antineoplastic Agents↗
PubMed2005

Sulfation of resveratrol in human liver: evidence of a major role for the sulfotransferases SULT1A1 and SULT1E1.

Sulfation of resveratrol, a polyphenolic compound present in grapes and wine with anticancer and cardioprotective activities, was studied in human liver cytosol. In the presence of 3'-phosphoadenosine-5'-phosphosulfate, three metabolites (M1-3) whose structures were identified by mass spectrometry and NMR as trans-resveratrol-3-O-sulfate, trans-resveratrol-4'-O-sulfate, and trans-resveratrol-3-O-4'-O-disulfate, respectively. The kinetics of M1 formation in human liver cytosol exhibited an pattern of substrate inhibition with a K(i) of 21.3 +/- 8.73 microM and a V(max)/K(m) of 1.63 +/- 0.41 microLmin(-1)mg(-1) protein. Formation of M2 and M3 showed sigmoidal kinetics with about 56-fold higher V(max)/K(m) values for M3 than for M2 (2.23 +/- 0.14 and 0.04 +/- 0.01 microLmin(-1)mg(-1)). Incubation in the presence of human recombinant sulfotransferases (SULTs) demonstrated that M1 is almost exclusively catalysed by SULT1A1 and only to a minor extent by SULT 1A2, 1A3 and 1E1, whereas M2 is selectively formed by SULT1A2. M3 is mainly catalysed by SULT1A2 and 1A3. In conclusion, the results elucidate the enzymatic pathways of resveratrol in human liver, which must be considered in humans following oral uptake of dietary resveratrol.

Adolescent↗
PubMed2004

Radiation therapy after breast-conserving surgery; first results of a randomised clinical trial in patients with low risk of recurrence.

To study the role of radiotherapy and tamoxifen after breast-conserving surgery (BCS) in patients with a favourable prognosis, a clinical trial was initiated by the German Breast Cancer Study Group. Between 1991 and 1998, 361 patients (pT1pN0M0, aged 45-75 years, receptor positive, grade I-II) were randomised to radiotherapy (yes/no) and tamoxifen for 2 years (yes/no) in a 2x2 factorial design; the exclusion of seven centres (14 patients) left 347 patients in the analysis. After a median follow-up of 5.9 years, 77 events concerning event-free survival have been observed. Since a strong interactive effect between radiotherapy and tamoxifen has been established, the results are presented in terms of the treatment effects for all four treatment groups separately. Mainly due to the presence of local recurrences, the event rate was about three times higher in the group with BCS only than in the other three groups. No difference could be established between the four treatment groups for distant disease-free survival rates. It is concluded that even in patients with a favourable prognosis, the avoidance of radiotherapy and tamoxifen after BCS increases the rate of local recurrences substantially.

Aged↗
PubMed2001

2-benzoxazolyl and 2-benzimidazolyl hydrazones derived from 2-acetylpyridine: a novel class of antitumor agents.

Here we describe the effects of novel benzoxazol-2-yl and benzimidazol-2-yl hydrazones derived from 2-pyridinecarbaldehyde and 2-acetylpyridine. The IC(50) values for inhibition of cell proliferation in KB-3-1, CCRF-CEM, Burkitt's lymphoma, HT-29, HeLa, ZR-75 and MEXF276L by most of the novel compounds are in the nanomolar range. In colony-forming assays with human tumor xenografts the compounds 2-actylpyridine benzoxazol-2-ylhydrazone (EPH52), 2-acetylpyridine benzoimidazol-2-ylhydrazone (EPH61) and 2-acetylpyridine 1-methylbenzoimidazol-2-ylhydrazone (EPH116) exhibited above-average inhibition of colon carcinoma (IC(50) = 1.3-4.56 nM); EPH52 and EPH116 also exhibited above-average inhibition of melanoma cells. As shown with human liver microsomes, EPH116 is only moderately metabolized. The compound inhibited the growth of human colon cancer xenografts in nude mice in a dose-dependent manner. Thiosemicarbazones derived from 2-formylpyridines have been shown to be inhibitors of ribonucleotide reductase (RR). The following results show that RR is not the target of the novel compounds: cells overexpressing the M2 subunit of RR and resistant to the RR inhibitor hydroxyurea are not cross-resistant to the novel compounds; inhibition of RR occurs at 6- to 73-fold higher drug concentrations than that of inhibition of cell proliferation; the pattern of cell cycle arrest in S phase induced by the RR inhibitor hydroxyurea is not observed after treatment with the novel compounds; and a COMPARE analysis with the related compounds 2-acetylpyrazine benzothiazol-2-ylhydrazone (EPH95) and 3-acetylisoquinoline benzoxazol-2-ylhydrazone (EPH136) showed that the pattern of these compounds is not related to any of the standard antitumor drugs. Therefore, these novel compounds show inhibition of colon cancers and exhibit a novel mechanism of action.

Animals↗
PubMed2001

The effect of bowel resection on survival in advanced epithelial ovarian cancer.

OBJECTIVE: FIGO stage III ovarian cancer is further categorized according to the size of tumor, but not according to the organs affected. In this study we evaluated the outcome of patients with and without macroscopic bowel involvement in stage III ovarian cancer. METHODS: This retrospective study analyzed the outcome of 194 ovarian cancer patients with FIGO III with and without bowel involvement who were operated on in our institution between 1985 and 1994. RESULTS: The study demonstrated that maximum tumor reduction without remaining macroscopic cancer offered the best overall survival times in FIGO III ovarian cancer patients. However, whenever the bowel was involved, even maximum bowel resections did not prolong survival compared to patients with remaining tumor after surgery. CONCLUSIONS: This retrospective study demonstrated that bowel involvement in ovarian cancer had a bad prognosis and that survival in these patients could not substantially be prolonged when the affected parts of bowel were resected. To further substantiate these findings, future studies on advanced ovarian cancer should differentiate between patients with and without bowel involvement.

Epithelial Cells↗
PubMed2001

Role of gonadotropins in malignant progression of sex cord stromal tumors produced by sequential auto- and isogenic transplantation of ovarian tissue in ovariectomized rats.

PURPOSE: In this study the effect of continuous stimulation of gonadotropins on sex cord stromal tumors in the rat was examined. METHODS: Sex cord stromal tumors were induced by transplantation of ovaries under the splenic capsule of ovariectomized rats. Beginning 180 days after transplantation, these tumors were taken out and cut into several pieces, which were then retransplanted (by isotransplantation) under the splenic capsule of 80 either intact or ovariectomized rats. RESULTS: Most of the tumor grafts grew up to a median size of 0.7 cm in ovariectomized rats. However, some of the tumors recovered from recipient rats that were retransplanted with donor tumors differed significantly from the others. Characterized by a high mitotic rate, nuclear atypia, size (up to 3.8 cm) as well as growth in intact animals, these tumors were defined as malignant. They could be kept in culture and always led to the development of metastases after retransplantation into other rats. CONCLUSION: Benign sex cord stromal tumors can show malignant growth after transplantation. This study for the first time demonstrates that gonadotropins are involved in the induction of ovarian malignancies.

Animals↗
PubMed2000

Characterization of synthetic polyelectrolytes by capillary electrophoresis.

Capillary electrophoresis in entangled polymer solutions was applied to determine the molecular mass and polydispersity of polyelectrolytes. The separation selectivities of different polyethylene glycols as buffer additive can be correlated to their average molecular mass. A universal curve correlating the selectivity and the molecular mass could be obtained by using the instrinsic viscosity of the polyethylene glycol. The separation of poly(2-vinylpyridine) standards was compared to the separation of poly(4-vinylpyridine) standards. An indirect detection system was developed to characterize the cationic polyelectrolyte polydiallyldimethyl ammonium chloride. Various polymers with oppositely charged groups (polycarboxybetaines) were investigated with respect to structure dependence, pH dependence and molecular mass dependence of interand intramolecular association.

Buffers↗
PubMed1999

The objective measurement of remission and progression in metastatic breast cancer by use of serum tumour markers. European Group for Serum Tumour Markers in Breast Cancer.

An established biochemical index for monitoring therapy in patients with metastatic breast cancer was tested prospectively in a multicentre study. The index uses two serum tumour markers--carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA15-3) along with erythrocyte sedimentation rate (ESR). 67 patients treated by either endocrine or chemotherapy had CA15-3, CEA and ESR measured at diagnosis of metastases and sequentially during therapy. Two markers, CA15-3 and CEA, were measured on a further 16 patients giving a total of 83 patients who were assessable for CA15-3 and CEA. Of the patients with CA15-3, CEA and ESR measured at diagnosis of metastases 84% (56/67) had elevation of 1 or more markers. During therapy the number with elevated marker(s) rose to 96% (64/67). Changes in the markers were in line with and often pre-dated therapeutic outcome as assessed by the International Union Against Cancer (UICC) criteria both for remission and progression. Patients without elevation of markers on diagnosis subsequently showed a rise in the marker(s) at or before documented disease progression by UICC. The 3 women in whom markers were at no time significantly elevated remain in remission. The results using CA15-3 and CEA were similar but 12% less patients were assessable. CA15-3 and CEA (with and without ESR) provide an objective method to guide therapy in patients with metastatic breast cancer.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1998

Increase of serum tumor marker concentrations by interferon-alpha.

Since it has been shown that the addition of interferon-alpha to ovarian cancer cells in vitro leads to an increase of CA125 in the cell culture supernatant it was the aim of our study to investigate whether the CA125 serum concentrations of patients with ovarian tumors could also be increased by injection of interferon-alpha in vivo. Nine patients with cystic ovarian tumors received 6 million IU interferon-alpha subcutaneously. CA125, CA15-3, and CEA were measured in defined time intervals during the following three days after interferon-alpha injection. In one patients with T1a N0 M0 ovarian cancer with normal serum levels of all markers before interferon-alpha application a massive increase of CA125 serum concentration was detected three days after injection. In the other 8 patients (5 benign tumors, 3 ovarian cancers) no marker increase was observed. In concordance with observations in cell cultures an increase of CA125 serum concentration after interferon-alpha injection was seen in one patient with early ovarian cancer and initially normal CA125 levels. If by the injection of interferon-alpha an increase of CA125 could regularly be induced in ovarian cancer patients, earlier detection of ovarian cancer seems possible.

Adult↗
PubMed1997

Is OVX1 a suitable marker for endometrial cancer?

The single most common cause leading to the diagnosis of endometrial cancer is postmenopausal bleeding. Although most patients with early-stage disease (FIGO stage I and II) can be cured, prognosis worsens considerably with increasing stage. While serum CA 125 levels are elevated only in a significant proportion of patients with advanced disease, recently a new serum marker (OVX1) for the detection of early-stage endometrial cancer was reported. Serum OVX1 levels were measured using an OVX1 radioimmunoassay (RIA) or enzyme immunoassay (EIA) in 192 patients with endometrial cancer. CA 125 levels were measured in 112 patients using the CIS ELSA CA 125 kit. Apparently healthy females had mean serum OVX1 levels measured with the OVX1-EIA of 1.34 +/- 0.74 U/ml, while patients with endometriosis had mean OVX1 serum levels of 3.15 +/- 2.45 U/ml. The mean OVX1 serum level for endometrial cancer patients was 2.00 +/- 1.32 U/ml. These values were 2.76 +/- 1.62, 6.10 +/- 4.66, and 5.37 +/- 3.49, respectively, using the OVX1-RIA assay. Applying a cutoff value of 2.8 U/ml, serum OVX1-EIA levels in endometrial cancer patients were increased in 25 of 127 patients (19.7%) with stage I disease, 5 of 17 patients with stage II (29.4%), 5 of 22 patients (22.7%) with stage III, and 4 of 11 patients (36.4%) with stage IV disease. Using the OVX1-RIA and a cutoff of 7.2 U/ml, serum levels were increased in 22 of 127 (17.3%) stage I, 6 of 17 (35.3%) stage II, 5 of 22 (22.7%) stage III, and 6 of 11 (54.5%) stage IV patients. Serum CA 125 levels, determined in a total of 112 patients, were elevated above 35 U/ml in 12 of 79 patients (15.2%) with stage I, 4 of 12 patients (33.3%) with stage II, 8 of 13 patients (61.5%) with stage III, and all of 8 patients (100%) with stage IV disease. While a good correlation between serum CA 125 levels and the clinical stage of the disease was found, no correlation could be detected for OVX1 and stage.

Antigens, Tumor-Associated, Carbohydrate↗
PubMed1996

Inhibition of cyclosporine and tetrahydrocannabinol metabolism by cannabidiol in mouse and human microsomes.

1. The in vitro and in vivo effects of cannabidiol on mouse and human liver microsomal metabolism of the immunosuppressive drug cyclosporine and the psychoactive compound tetrahydrocannabinol have been examined. 2. Preincubation of mouse or human liver microsomes with cannabidiol decreased the formation of all detectable cyclosporine metabolites by 73-89%. 3. In vivo cannabidiol treatment of mouse similarly decreased the formation of all detectable cyclosporine metabolites by 60-86%. 4. Preincubation of human liver microsomes with cannabidiol selectively decreased the formation of tetrahydrocannabinol metabolites catalyzed by cytochrome P4503A by 60% but had no effect on P4502C9-catalyzed metabolites. 5. Cannabidiol has the potential to clinically affect cyclosporine metabolism which may result in increased cyclosporine blood levels and an increase in its toxic side effects, and likewise may also affect tetrahydrocannabinol and its metabolite levels in man.

Animals↗
PubMed1996

Modulation of 5-fluorouracil resistance in human colon tumor cell lines by azidothymidine.

5-fluorouracil (5-FU), an inhibitor of thymidylate synthase (EC 2.1.1.45), is clinically used in the treatment of several solid tumors, including colorectal, head and neck, gastric, and pancreatic cancer. The drug effectively inhibits deoxynucleoside triphosphate de novo synthesis. However, this inhibition can be circumvented by increased thymidine kinase (EC 2.7.1.21) activity. In the present study we examined the effects of 5-FU combined with azidothymidine (AZT), a competitive inhibitor of thymidine kinase in human colon tumor cells in vitro, including three 5-FU resistant cell lines. The cells were simultaneously incubated with various concentrations of 5-FU (0.015 to 150 microM) and AZT (20 to 300 microM) for 6 days. 5-FU alone yielded an IC50 of 18 microM in the parental CCL 227 cell line and IC50s of 470 and 1100 microM in the 5-FU resistant cell lines as determined by a MTT chemosensitivity assay. Addition of 100 microM AZT alone, a drug concentration that can be achieved in patients, had no effect on the growth of the cell lines examined. However, when added simultaneously with 5-FU, the IC50s of 5-FU synergistically decreased to 10 microM in the sensitive and to 360 or 760 microM in the resistant cell lines, respectively. Our results demonstrate that the combination of 5-FU with AZT synergistically inhibited the growth of 5-FU resistant cells, suggesting the use of 5-FU in combination with AZT for the treatment of 5-FU sensitive as well as resistant human colon tumors.

Antimetabolites, Antineoplastic↗
PubMed1994

Identification of insulin and insulin-like growth factor I (IGF I) receptors in ovarian cancer tissue.

The objective of this study was to test if specific insulin and insulin-like growth factor I (IGF I) receptors are expressed in ovarian cancer tissue. Thirteen tissue specimens from primary ovarian cancers, 1 specimen from a primary peritoneal carcinoma, 10 specimens from metastatic lesions of ovarian carcinomas, and 4 specimens from recurrent ovarian cancers together with 13 normal ovaries were tested for their content of insulin and IGF-I receptors, by the application of specific insulin and IGF-I receptor radioimmunoassays. The insulin receptor (IR) and IGF-I receptor (IGF R) content in the primary tumors varied between 23.8-321.4 and 16.4-554.2 ng/0.1 mg DNA, respectively. Metastatic lesions contained between 12.3 and 226.7 ng IR/0.1 mg DNA and between 7.5 and 459.4 ng IGF R/0.1 mg DNA. In recurrent tumors the receptor concentrations were in the range of 41.5-79.8 and 48.9-160.9 ng/0.1 mg DNA for insulin and IGF-I receptors, respectively. Normal ovarian tissue contained between 12.2 and 150.1 ng IR and between 21.4 and 420.1 ng IGF R per 0.1 mg DNA, respectively. As both insulin and IGF-I receptors are present in ovarian cancer tissue, the effects of insulin and IGF-I as potential growth factors in ovarian cancer should be further investigated.

Adult↗
PubMed1994

[Hermann von Helmholtz (1821-1894). On the 100th anniversary of his death].

In Helmholtz's judgement it was a favourable fate to have been thrown under medical students and into medicine with a sense of geometrics and with knowledge of physics. The result of this favourable combination was the invention of the ophthalmoscope and the Handbook of Physiologic Optics. Those were the foundations of all physiological aspects of ophthalmology, which were taken up and completed by A. v. Graefe and his colleagues. The ophthalmoscope was invented on the occasion of his university-courses, when Helmholtz tried to explain the theory of the red reflex of the pupil. Stimulated by Helmholtz in the following year Ruete developed the method of indirect ophthalmoscopy. This method at once was simplified again by Helmholtz in an extraordinary way. These two publications by Helmholtz contain all further developments involved with the ophthalmoscopy as an anticipation. The Handbook of Physiologic Optics is the first encyclopedic monography of this topic. Many new inventions are extremely valuable for the practical requirements of ophthalmologists. The first chapter about dioptrics contains the description of the Ophthalmometer, a new instrument to measure the astigmatism. In the chapter about visual sensations a clear survey about light- and colour sense is given. The colour deficiencies which were found during the decades before are introduced as the most important arguments for the three-component-theory of human colour vision. The prototype of a telestereoscope is demonstrated in the third chapter about visual perception.(ABSTRACT TRUNCATED AT 250 WORDS)

Germany↗