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G Bartsch

Publications and source records attributed to G Bartsch.

At least 145 records · Page 8Linked to original sources
PubMed1998

Interleukin-6 regulates prostate-specific protein expression in prostate carcinoma cells by activation of the androgen receptor.

Interleukin-6 (IL-6) levels are frequently elevated in sera of patients with metastatic prostate cancer. IL-6 receptors are expressed in prostate cancer cell lines, as well as in benign prostate hyperplasia and prostate cancer tissue specimens. The androgen receptor (AR) is a key transcription factor that is present in all stages of prostate carcinoma, even in therapy-refractory tumors. In an attempt to investigate possible cross-talk between IL-6 and androgen signal transduction cascades, we tested the effects of this cytokine on AR transcriptional activity. The regulation of AR activity by IL-6 was studied in DU-145 cells, which were cotransfected with the androgen-responsive reporter plasmid ARE2TATACAT and the AR expression vector pSG5AR. We show that IL-6 up-regulates AR activity in a ligand-independent manner, as well as synergistically, with very low doses of the synthetic androgen methyltrienolone (5-10 pM). Therefore, AR activation by IL-6 may be operative in prostate cancer patients who have decreased androgen levels because of androgen ablation therapy. The maximal induction of reporter gene activity by IL-6 alone (50 ng/ml) was 67% of that stimulated by 1 nM of methyltrienolone. The nonsteroidal antiandrogen bicalutamide (Casodex) nearly completely inhibited AR activation by IL-6. IL-6 effects on AR activity were also abolished or greatly reduced by inhibitors of protein kinase A and C and mitogen-activated protein kinase pathways. In concordance with the results obtained in DU-145 cells, IL-6 induced AR-regulated prostate-specific antigen mRNA and protein in LNCaP cells. Stimulation of prostate-specific antigen protein secretion by IL-6 was antagonized by bicalutamide and inhibitors of protein kinase A and mitogen-activated protein kinase signaling pathways. Taken together, our data show for the first time that IL-6 is a nonsteroidal activator of the AR and that this activation is implicated in the regulation of prostate-specific proteins. Keeping in mind that IL-6, its receptor, and the AR are expressed in prostate cancers, cross-talk between IL-6 and AR signaling pathways may have clinical significance.

Down-Regulation↗
PubMed1998

Expression of Lewis carbohydrate antigens in metastatic lesions from human prostatic carcinoma.

BACKGROUND: Monoclonal antibodies B1 and B3 react with Lewis(y) and related carbohydrate antigens, which are abundant in many solid tumors. These antibodies, when conjugated to a toxin, have been used to target a variety of cancers. Treatment options for advanced prostate cancer are very limited, and there is a need to develop new therapies. In this study, we have asked whether antibodies B1 and B3 react with metastatic lesions from human prostatic carcinoma. METHODS: Indirect streptavidin-biotin peroxidase immunohistochemistry was performed on formalin-fixed specimens from prostate cancer metastases. A total of 6 lymph node metastatic samples from patients who did not receive endocrine treatment and specimens of 14 distant metastases from patients who failed hormonal therapy were obtained. RESULTS: Of the samples, 6 lymph node and 11 distant metastases stained for B1. In the case of B3 staining, 6 lymph node and 10 distant metastatic lesions were positive. In about half of these metastatic samples, more than 40% of cells were immunoreactive with either antibody. Two metastatic samples stained neither for B1 nor for B3 antibody. In general, B1 staining intensity was stronger in samples in which more than 40% of cells were positive. CONCLUSIONS: Our results suggest that B1 and B3 immunoconjugates could be applied to target a substantial percentage of prostate cancer metastases.

Antibodies, Monoclonal↗
PubMed1998

Restoration of voluntary emptying of the bladder by transplantation of innervated free skeletal muscle.

BACKGROUND: On the basis of studies with animals and experience with functioning muscle transfer in plastic surgery, we have developed a surgical technique to restore detrusor function for patients with bladder acontractility in whom there is no treatment alternative. METHODS: Three patients (aged 26 years, 28 years, and 68 years) with bladder acontractility as a result of spinal-cord injury (two patients) and chronic overdistension (one patient), who required catheterisation for bladder emptying for 5 years, 2 years, and 2 years, respectively, took part in our study. The patients were treated with microneurovascular free transfer of autologous latissimus dorsi muscle to the bladder to restore detrusor function. Follow-up included clinical and urodynamic evaluation, colour doppler sonography, intravenous urography, and flow-mode computerised tomography. FINDINGS: The three patients voluntarily emptied their bladders at 16 weeks, 16 weeks, and 30 weeks after surgery, respectively. There was no need for further catheterisation throughout the follow-up period. On urodynamic assessment at 12 months after the operation bladder capacity was found to be 600 mL, 600 mL, and 650 mL, residual urinary volume 0 mL, 50 mL, 90 mL, and maximum flow rate 26 mL/s, 25 mL/s, and 18 mL/s, respectively. Activity at the transplanted latissimus dorsi was confirmed by ultrasonography and flow-mode computerised tomography. INTERPRETATION: Microneurovascular free transfer of latissimus dorsi muscle to functionally restore a deficient detrusor muscle has proved to be successful for the three patients in our study. This technique may also be an option to restore the function of other smooth-muscle organs.

Adult↗
PubMed1998

Differential deactivation of human dendritic cells by endotoxin desensitization: role of tumor necrosis factor-alpha and prostaglandin E2.

The endotoxin (lipopolysaccharide)-induced cytokine response is followed by a state of unresponsiveness to lipopolysaccharide (LPS) referred to as LPS tolerance or endotoxin desensitization. LPS tolerance, which can be experimentally induced in vitro and in vivo, is also known to occur in septic disease. Here, we evaluated whether dendritic cells (DC), the most potent antigen-presenting cells, are also subject to this phenomenon. Single doses of LPS added at the initiation of DC culture inhibited in a dose-dependent fashion the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-10 (IL-10), and IL-12, but not the production of IL-8, in response to a second LPS challenge in day-5 DC. In addition, the LPS-induced expression of the CD83 maturation antigen was inhibited in these cells. Moreover, the endocytic activity of DC generated in the presence of LPS was dramatically reduced. DC desensitized with LPS were potent stimulators of T-cell proliferation but poor inducers of interferon-gamma (IFN-gamma) production in the allogeneic mixed leukocyte reaction. TNF-alpha and prostaglandin E2, two major products of LPS stimulation, could replace LPS for the induction of tolerance to LPS. Moreover, treatment of desensitized DC with TNF-alpha plus prostaglandin E2 fully restored CD83 expression and partially restored IL-12 production as well as the IFN-gamma-inducing activity of DC in the mixed leukocyte reaction. Our data show that human DC are highly susceptible to the induction of LPS tolerance, which seems to be a state of differential deactivation in which some functions are impaired whereas others are retained. Tolerization at the level of the professional antigen-presenting cell by inflammatory mediators may play an important role in septic disease and in the origin of cancers associated with chronic inflammation.

Antigens, CD↗
PubMed1998

Expression, structure, and function of androgen receptor in advanced prostatic carcinoma.

BACKGROUND: Endocrine therapy for prostate cancer aims to reduce the levels of circulating androgen or to inhibit androgen action by blocking the androgen receptor in the prostate, or both. Studies in various animal and human prostate cancer models suggested that there may be a downregulation of androgen receptor during prostate cancer progression. Recent work, however, showed androgen receptor expression in all stages of prostate cancer. The presence of mutant androgen receptors in a portion of prostate cancers and receptor activation in the absence of androgen or in the presence of low androgen concentrations is discussed within this context. METHODS: This review attempts to summarize the literature on androgen receptor expression in vitro and in vivo, as well as structural and functional alterations and communication between androgen signal transduction cascade and other signaling pathways. CONCLUSIONS: Prostate tumors adapt to an environment with low androgen supply by using a hyperactive androgen receptor. The mechanisms involved are mutations of the androgen receptor generating receptors with broadened activation spectrum, increased receptor expression, and activation by interaction with other signaling pathways.

Androgen Antagonists↗
PubMed1998

Human monocyte-derived dendritic cells produce macrophage colony-stimulating factor: enhancement of c-fms expression by interleukin-10.

Human monocyte-derived dendritic cells (DC) generated with granulocyte-macrophage colony-stimulating factor (GM-CSF) and IL-4 express c-fms (CD115), the receptor for macrophage-CSF (M-CSF). Expression of c-fms on monocyte-derived DC has been interpreted as the susceptibility of these cells to M-CSF-induced macrophage development. We show here that homogeneous cultures of CD14 DC constitutively produced large amounts of M-CSF. However, presence of M-CSF neither induced macrophage development nor did it prevent terminal maturation into CD83+ DC. M-CSF production by DC was driven by GM-CSF and inhibited by the specific phosphatidylinositol 3-kinase inhibitor wortmannin. M-CSF synthesis was rapidly induced during the first 24 h of DC culture and then declined during the 5-day culture period. Replating of the cells, which was associated by a transient adherence, always induced a strong up-regulation of M-CSF synthesis. Addition of recombinant IL-10 to DC cultures enhanced c-fms expression and induced macrophage development as measured by the strong up-regulation of CD14 expression as well as by enhanced expression of the Fcgamma receptors I, II, and III (CD64, CD32, CD16). Our data demonstrate that immature monocyte-derived DC produce M-CSF which does not induce macrophage development, despite the surface expression of c-fms on DC. IL-10 appears to induce macrophage development by up-regulating c-fms and, thereby, enhancing the sensitivity of the cells to endogenously produced M-CSF.

Androstadienes↗
PubMed1998

Nordihydroguaiaretic acid blocks secretory and endocytic pathways in human dendritic cells.

Nordihydroguaiaretic acid (NDGA), an antioxidant and inhibitor of the lipoxygenase arm of the arachidonic acid metabolism, was recently demonstrated to inhibit transport of secretory proteins to the Golgi complex. We have investigated the effects of NDGA on the secretory and endocytic activity of cultured human blood dendritic cells (DC). Treatment with NDGA strongly diminished cytokine secretion by DC. Moreover, NDGA reduced in a dose- and time-dependent fashion fluid phase as well as receptor-mediated endocytosis in DC. Zileuton and MK-886, specific inhibitors of 5-lipoxygenase and 5-lipoxygenase-activating protein, respectively, had no effect. Likewise, N-acetyl-L-cysteine, a thiol antioxidant precursor of glutathione, did not affect DC function. Finally, serum remarkably protected the cells from the inhibitory effects of NDGA. Our data demonstrate that NDGA not only disrupts vesicular transport along the secretory route but is also a potent inhibitor of the endocytic pathways in human DC and that NDGA has inhibitory properties different from those described.

Cells, Cultured↗
PubMed1998

Intraurethral ultrasound: diagnostic evaluation of the striated urethral sphincter in incontinent females.

The aim of our study was to evaluate the striated urethral sphincter (rhabdosphincter) in incontinent females by means of intraurethral ultrasound (IUUS). Thirty-four incontinent and 11 continent female patients were examined by means of 12.5-MHz endoluminal ultrasound (US). The distance between the inner contour of the sphincter muscle and the US catheter was measured in the contracted and the non-contracted condition. The US findings were correlated with those obtained by urodynamic studies. Partial or complete loss of sphincter function was detected in patients with stress urinary incontinence (SUI). Reduced sphincter function was not observed in patients with urge incontinence and continent volunteers. The findings on US were found to correlate well with the grade of SUI. The IUUS technique offers the benefit of direct visualization of the sphincter mechanism. Therefore, endoluminal US may become an important adjunct in the diagnostic evaluation of SUI and will possibly provide new insights for a better therapeutic strategy.

Adult↗
PubMed1998

Three-dimensional computed tomography of the reconstructed lower urinary tract: technique and findings.

The aim of this pilot study in 54 patients was to improve the visualization of the anatomy and postoperative changes in the pelvic topography after bilateral ureteroileal urethrostomy, using surface rendering of electron beam CT (EBCT) data for the 3D display. Fifty-four patients (39 men and 15 women) were scanned with an EBCT unit between 3 and 110 months after performing orthotopic ureteroileal urethrostomy ("Hemi-Kock") or ureteroileal rectosigmoidostomy. Various parameters and spatial viewing points were used in the 3D reconstruction, which was performed interactively on external workstations with commercially available software. The anti-reflux nipple was visualized as a distinct structure in all patients. In 8 patients with an interval of more than 12 months between surgery and CT, the pouch had developed an ovoid shape almost indistinguishable from the original bladder. The segmented data sets were partly animated to display the anatomy as virtual endoscopy. Three-dimensional depiction and virtual endoscopy of the neobladder using EBCT are a new way of imaging the postoperative anatomy. Its clinical efficacy in the diagnosis of inconclusive postoperative morbidity, especially voiding problems, and planning of necessary therapy have to be the subject of further evaluation.

Adult↗
PubMed1998

Laparoscopic surgery for pheochromocytoma: adrenalectomy, partial resection, excision of paragangliomas.

PURPOSE: Surgical treatment of pheochromocytoma includes adrenalectomy, adrenal sparing surgery and excision of extraadrenal paragangliomas. We report our experience using laparoscopy for these procedures. MATERIALS AND METHODS: Between June 1992 and November 1997, 19 patients underwent laparoscopic surgery for pheochromocytoma. Of the patients 14 had solitary tumors, and 4 presented with bilateral pheochromocytomas and 1 or 2 additional paragangliomas. In 1 patient a recurrent pheochromocytoma was found in the contralateral adrenal following previous right adrenalectomy. One patient each had myocardiopathy, amaurosis and stroke secondary to severe hypertension. Two patients were pregnant. RESULTS: All solitary tumors were treated with laparoscopic adrenalectomy. Laparoscopic adrenal sparing surgery (4 cases, 2 bilateral) and bilateral adrenalectomy (1) were performed for multiple familial pheochromocytoma, and all paragangliomas were excised simultaneously. The pregnant patients underwent surgery at 16 and 20 weeks of gestation, respectively. All procedures were completed as planned. The rate of minor intraoperative and postoperative complications was 11% and 16%, respectively, and there were no major complications. In all patients the catecholamine levels returned to normal and no residual tumors were found at followup. None of the patients undergoing partial resection required steroid replacement therapy. CONCLUSIONS: In experienced hands, laparoscopic surgery for solitary and multiple pheochromocytoma and paraganglioma is feasible and safe, and does not increase the specific risks associated with pheochromocytoma surgery.

Adrenal Gland Neoplasms↗
PubMed1998

The female urethral sphincter: a morphological and topographical study.

PURPOSE: We reassess the anatomy and topography of the female urethral sphincter system and its innervation in regard to urethra sparing anterior exenteration and other surgical procedures. MATERIALS AND METHODS: Anatomical and histological studies were performed on 9 fetal specimens and 4 adult cadavers. Using graphics software the anatomical structures of the true pelvis were reconstructed based on computerized tomography cross sections and digitized histological sections. On the adult cadavers anterior exenteration was performed to study the implications of the isolated urethra and its sphincter mechanism. RESULTS: Strata of connective tissue were found to divide the smooth muscles of the proximal two-thirds of the female urethra into 3 layers. Computer guided 3-dimensional reconstruction of digitized histological sections showed that thin fibers of the pelvic plexus course to this part of the urethra. The majority of these fibers may be preserved by carefully dissecting the bladder neck and the proximal portion of the urethra, leaving the lateral vaginal walls intact. The striated rhabdosphincter, which is innervated by fibers of the pudendal nerve, was in the caudal third of the urethra. CONCLUSIONS: A well-defined sphincteric structure or sphincter could not be anatomically recognized in the bladder neck region. The majority of rhabdosphincter fibers were found in the middle and caudal thirds of the urethra. Thus, in patients undergoing removal of the bladder neck and part of the proximal portion of the urethra continence can be maintained by the remaining urethral sphincter system, provided that innervation remains essentially intact.

Cadaver↗
PubMed1998

Transurethral ultrasound: evaluation of anatomy and function of the rhabdosphincter of the male urethra.

PURPOSE: A combined anatomic-sonographic study was undertaken to investigate whether the anatomical arrangement and the contractions of the rhabdosphincter of the male urethra could be visualized by transurethral ultrasound. Furthermore, this new technique was compared with standard urodynamic tests. MATERIALS AND METHODS: In 7 cadavers transurethral ultrasound was performed to define sono-morphological criteria of the rhabdosphincter, and the sonographic pictures were then compared to histological sections. In 48 patients the rhabdosphincter of the male urethra was investigated by transurethral ultrasound and urodynamic techniques. Of these patients 40 were completely continent after radical prostatectomy and 8 presented with urinary stress incontinence after transurethral resection of the prostate or radical prostatectomy. The decrease of the distance between the rhabdosphincter and the transducer during contraction served as quantitative parameter for the contractility of the muscle. RESULTS: The anatomical arrangement and contractions of the rhabdosphincter loop could be clearly visualized on transurethral ultrasound (during contraction the rhabdosphincter retracts the urethra, pulling it towards the rectum). Ultrasound showed scars in 3 patients with postoperative urinary stress incontinence, thinning of the muscle in 3 complete atrophy of the rhabdosphincter in 2 and minimal contractions of the rhabdosphincter in 1. Urethral closure pressures were decreased and decrease in rhabdosphincter-transducer distance was statistically significantly decreased in the incontinent patients. CONCLUSIONS: Our sono-morphological data and anatomical histological results strongly suggest that the rhabdosphincter constitutes the main component of the continence mechanism in post-prostatectomy patients. Unlike urethral pressure profiles, which can only reveal zones of higher intraluminal pressure between the bladder and the penile urethra, transurethral ultrasound is highly specific for measurement of the function of the rhabdosphincter.

Humans↗
PubMed1998

Measurement of serum prostate-specific membrane antigen, a new prognostic marker for prostate cancer.

OBJECTIVES: To describe current results with Western blot assay for prostate specific membrane antigen (PSMA) using 7E11.C5 antibody and the development of an additional antibody measurement for PSMA by a new sandwich immunoassay. METHODS: A population of patients from a screening group, from a difficult diagnostic group, from a pre- and postoperative radical prostatectomy group, and from a group with metastatic disease followed for a serial period, provided the serum values for a prospective assessment of PSMA by Western blot assay. A new monoclonal antibody was sought, reacting to the C-terminal region of PSMA in order to develop a sandwich radioimmunoassay. RESULTS: PSMA values in screened patients correlate with the more advanced stage of the cancers determined. In postprostatectomy patients, the PSMA value corresponds more with preoperative values and with the values of those with a poor clinical course. In difficult diagnostic cases, the PSMA value is increased, specifically in hormone-refractory cases and particularly in those cases judged by other criteria, such as the National Prostatic Cancer Project, to be in clinical progression compared with those judged to be in clinical remission. The level of PSMA value appears to be independent of homogeneous tumor volume and to be more related to that of prior hormone treatment, or to where prostate cancer cells can be documented to be outside the prostate. A new monoclonal antibody, 3F5.4G6, reacts with the extracellular domain of PSMA near the C-terminal region. This is in contrast to the previously measured antibody 7E11.C5, which reacts with an N-terminal epitope. 3F5.4G6 recognizes the same PSMA protein as does 7E11.C5. The epitopes are essentially at opposite ends of the molecule. The 3F5.4G6 antibody reacts with the LNCaP line but not with DU145, or PC3. These two antibodies to PSMA are well suited for use in a new sandwich immunoassay. CONCLUSIONS: PSMA provides a prostatic cancer serum test by using Western blot, which suggests a clinical prognostic value not seen with other markers. New antibodies, such as 3F5.4G6, reacting with the extracellular domain of PSMA combined with 7E11.C5, appear to offer an opportunity for a new sandwich immunoassay.

Antibodies, Monoclonal↗
PubMed1998

Interleukin 1beta mediates the modulatory effects of monocytes on LNCaP human prostate cancer cells.

Proliferative and secretory responses in androgen-sensitive prostate cancer LNCaP cells are regulated by steroid and peptide hormones and by differentiation-promoting substances. In the present study, we evaluated whether peripheral blood monocytes that exhibit anti-tumour activity in haematopoietic and solid tumours influence growth and secretion in the LNCaP cell line. For this purpose, LNCaP cells were incubated with monocyte-conditioned medium (MCM), and proliferation as well as expression of androgen receptor (AR) and secretion of prostate-specific antigen (PSA) were assessed. Conditioned medium from monocytes reduced proliferation in a dose-dependent manner. Incubation with 40% MCM caused a 50% reduction in cell proliferation. AR protein decreased by 70% and PSA levels in supernatants from LNCaP cells were reduced by approximately 80% following treatment with MCM. We focused on the contribution of two major products of activated monocytes, prostaglandin E2 and interleukin 1beta (IL-1beta), to the MCM modulatory action. LNCaP cells treated with prostaglandin E2 showed neither a reduction in proliferation nor a down-regulation of AR and PSA levels. The effects of MCM on cellular proliferation, AR protein and PSA secretion were abolished by pretreatment of MCM with a neutralizing anti-IL-1beta antibody. In addition, recombinant IL-1beta was able to replace MCM for the inhibition of proliferation and down-regulation of AR and PSA proteins. LNCaP cells were shown to express the IL-1beta receptor type 1, which transduces IL-1beta signal. Our findings reveal that monocyte-derived IL-1beta inhibits the proliferation of androgen-responsive prostate tumour cells and reduces AR and PSA levels.

Cell Division↗
PubMed1998

Activation of human dendritic cells by bacillus Calmette-Guerin.

PURPOSE: Dendritic cells are the most potent antigen presenting cells capable of initiating antitumor immune responses. We previously showed that bacillus Calmette-Guerin (BCG) stimulates cultured human dendritic cells. We extended these studies and tested the ability of cultured human dendritic cells to express interleukin IL-8 in response to BCG. We also investigated the T cell stimulatory potential of BCG treated dendritic cells in mixed leukocyte reactions. MATERIALS AND METHODS: Dendritic cells were obtained by culturing plastic adherent mononuclear cells from peripheral blood for 6 days in the presence of granulocyte-macrophage colony-stimulating factor and IL-4. Spontaneous and BCG stimulated IL-8 protein release into culture supernatants was measured by a quantitative immunoassay. IL-8 gene transcription was assessed by reverse transcription-polymerase chain reaction. Untreated and BCG exposed dendritic cells were compared as stimulators of allogeneic T cell proliferation, measured as [3H]thymidine incorporation. RESULTS: BCG stimulated IL-8 messenger ribonucleic acid expression and IL-8 protein release. IL-8 secretion occurred in a dose and time dependent fashion. BCG induced IL-8 release was further enhanced in the presence of indomethacin. BCG treated dendritic cells were much more potent T cell stimulators than untreated dendritic cells. CONCLUSIONS: These data demonstrate that BCG enhances the production of IL-8, a potent chemokine of T cells and granulocytes, as well as the T cell stimulatory potential of human dendritic cells.

Antibodies, Monoclonal↗
PubMed1998

Analysis of a mutant androgen receptor offers a treatment modality in a patient with partial androgen insensitivity syndrome.

OBJECTIVES: In male pseudohermaphroditism patients, we have detected androgen receptor (AR) gene mutations as the underlying molecular defect. The properties of these mutant receptors regarding hormone binding and transactivation were characterized. In a newborn patient with partial androgen insensitivity syndrome caused by an AR gene point mutation, the functional analysis of the mutated AR offers a possible treatment modality. METHODS: Specific binding of dihydrotestosterone in the patient's genital skin fibroblasts, thermostability, and 5 alpha-reductase activity were evaluated. Furthermore, an AR gene mutation was detected by direct sequencing. The ability of the mutant receptor to activate androgen-responsive elements in the DNA was determined by recreating an AR expression vector and cotransfection experiments. RESULTS: The newborn patient with partial androgen insensitivity showed a qualitative and quantitative binding defect. A point mutation in the ligand binding domain was identified as the underlying cause. Transactivation assays demonstrated that increasing androgen concentration can restore the function of the mutated receptor completely. Therefore, the patient received androgen stimulation which resulted in good growth of his external genitalia and underwent surgical correction in the male direction. CONCLUSIONS: Diagnosis and therapy in affected patients will be improved identifying the molecular mechanisms that cause the various forms of sex ambiguity. Exact characterization of AR activation and function may offer a possible treatment modality in patients with the androgen insensitivity syndrome. Our results led to a surgical correction of our newborn patient in the male direction.

3-Oxo-5-alpha-Steroid 4-Dehydrogenase↗
PubMed1998

Dendritic cell-based immunotherapy of renal cell carcinoma.

Dendritic cells potently stimulate antigen-specific immune responses and recent data indicate that they are also capable of eliciting antitumor immune responses. We are performing a pilot study which tests the safety and efficacy of antigen-loaded, cultured blood dendritic cells in patients with metastatic renal cell carcinoma. Dendritic cells are simultaneously pulsed with lysate from autologous tumor cells and with the immunogenic protein keyhole limpet hemocyanin. During the pulse, the cells are activated with a combination of tumor necrosis factor-alpha and prostaglandin E2. Patients receive 5-10 X 10(6) dendritic cells per intravenous infusion and up to six infusions at monthly intervals. The first results demonstrate that this treatment modality is very well tolerated and can be associated with strong immunological and clinical responses. The present article discusses the importance of dendritic cell maturation and the role of helper antigens in dendritic cell-based immunotherapy.

Animals↗