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J Vieweg

Publications and source records attributed to J Vieweg.

34 records · Page 2Linked to original sources

Considerations for the use of cytokine-secreting tumor cell preparations for cancer treatment.

Limited efficacy of chemotherapy in most solid tumors has revived interest in immunotherapeutic approaches for cancer. One novel form of immunotherapy is the use of cancer vaccines consisting of tumor cells genetically engineered to secrete cytokines. The rationale for this immunization strategy is based on the existence of tumor-specific antigens, on the importance of the cellular arm of the immune system in mediating an effective antitumor response, and on the role of cytokines in regulating the cellular immune response. Such tumor vaccines showed considerable promise in various animal models and induced potent antitumor immunity in the host, which led to regression of established tumors and, moreover, produced immunological memory protecting animals from a subsequent tumor challenge at a distant site. Translated to the human patient, this implies that genetically modified tumor vaccines may be able to eradicate or reduce existing tumor deposits to subclinical levels as well as provide long-term protection from regrowth of tumor cells. This report will review and discuss the concept and rationale for the use of cytokine-secreting tumor vaccines for the treatment of human malignancies.

Animals↗

Gene therapy approaches in urologic oncology.

The tools and concepts of cytokine gene-based immunotherapy are being applied to the development of potentially effective new adjuvant treatment modalities for urologic malignancies. In preclinical models for the most prevalent urologic cancers, such as renal cell, bladder, and prostate carcinoma, it was shown that cytokine secreting, growth inactivated, tumor cell preparations (1) are capable of inducing a T-cell response against even nonimmunogenic tumors, (2) have considerable therapeutic benefit in tumor bearing animals, and (3) establish effective immunologic memory in cured animals. These studies have advanced further our understanding of the efficacy and therapeutic use of cytokine secreting tumor cells and form the rationale for translating these preclinical results into a clinical setting. It is realistic to speculate that in the foreseeable future alternative or complementary approaches to cytokine gene-based immunotherapy will be developed that would augment immune responses in cancer patients. Genetically modified dendritic cells transduced with genes encoding isolated tumor rejection antigens or costimulatory signals, such as B7, may be even more potent immune stimulators to induce systemic immune responses. Although animal studies have shown considerable promise and investigational clinical trials are underway, additional research and further development still is required to realize the full benefit of this approach, and some forms of cancer eventually may respond to this form of cancer immunotherapy.

Animals↗

The role of pelvic lymphadenectomy and radical cystectomy for lymph node positive bladder cancer. The Memorial Sloan-Kettering Cancer Center experience.

BACKGROUND: The impact of pelvic lymph node dissection (PLND) on the survival of patients with lymph node positive bladder cancer is controversial. METHODS: The authors retrospectively analyzed the long term and disease free survival among 140 patients with lymph node positive disease having radical cystectomy and bilateral PLND at the Memorial Sloan-Kettering Cancer Center between 1980 and 1988. They also sought to identify prognostic variables for recurrence and survival. RESULTS: Of the 140 patients, 36 (25.7%) were found to be tumor free, with 22 (15.7%) followed longer than 5 years. Regression analysis identified P-category as the only prognostic parameter influencing survival. Patients with tumors confined to the bladder (< or = P3a) had a 52.6% 5-year survival rate compared with 23.4% among those with extravesical (> or = P3b) tumors. N-category was a significant predictor for recurrence but not survival. CONCLUSIONS: As judged from this analysis, radical cystectomy and a systematic PLND alone can provide favorable outcome in some patients with regional nodal metastases from bladder cancer. The survival advantage is most pronounced in patients with low stage primary tumors. Stage migration and patient selection may have biased these findings.

Combined Modality Therapy↗

Immunotherapy of prostate cancer in the Dunning rat model: use of cytokine gene modified tumor vaccines.

Adenocarcinoma of the prostate is the most common cancer in men. The majority of cancers are discovered once they have already metastasized, and there is no effective therapy for prostatic cancer at this stage. The use of cytokine-secreting tumor cell preparations as therapeutic vaccines for the treatment of advanced prostate cancer was investigated in the Dunning rat R3327-MatLyLu prostatic tumor model. IL-2 secreting, irradiated, tumor cell preparations were capable of curing animals with s.c. established tumors, and induced immunological memory that protected animals from subsequent tumor challenge. Immunotherapy was less effective when tumors were induced orthotopically, but nevertheless led to improved outcome, significantly delaying, and occasionally preventing, recurrence of tumors after resection of the cancerous prostate. Granulocyte-macrophage colony stimulating factor secreting tumor cell preparations were less effective, and interferon-gamma secreting cells had only a marginal effect. Induction of a potent immune response in tumor bearing animals against the nonimmunogenic MatLyLu tumor supports the view that active immunotherapy warrants further investigation as a potential therapeutic approach to prostate cancer.

Adenocarcinoma↗

An experimental model simulating local recurrence and pelvic lymph node metastasis following orthotopic induction of prostate cancer.

In order to develop an animal model that more closely simulates the organ environment and metastatic routes of human prostatic cancer, R3327-MatLyLu tumors were induced by orthotopic implantation in the ventral prostatic lobe of Copenhagen rats. This procedure reproducibly resulted in metastatic spread of the intraprostatic tumor to the pelvic and retroperitoneal lymph nodes, and invariably to the lungs. Further, a tumor recurrence model was established using an approach that combined orthotopic tumor implantation and subsequent surgical resection of the primary tumor. When prostatectomy was carried out 4 days or more after induction, tumors recurred locally in all animals. The surgical procedures described may provide an animal model to test the in vivo response to experimental adjuvant treatment protocols for advanced prostate cancer. Immunological studies are now in progress using cytokine gene-modified prostatic tumor cells as cellular antitumor vaccines in orthotopically established R3327-MatLyLu tumors.

Animals↗

Immunotherapy of cancer using cytokine gene-modified tumor vaccines.

Distant metastasis is the major cause for therapeutic failures in clinical oncology. Active immunotherapy of patients with low tumor burden would not only contribute to further reduction of the remaining tumor burden to subclinical levels, but it would also establish a constant state of immunity, i.e. immunological memory, that could protect the patient from recurrence of disease. Studies employing rodent tumor models with little or no intrinsic immunogenicity have shown that genitically modified tumor cell preparations consisting of irradiated tumor cells transduced with and expressing cytokines such as IL-2, IL-6, IFN-gamma or GM-CSF were capable of inducing the regression of a preexisting tumor burden and cure animals from their disease. Moreover, in some instances the cured animals have retained immunological memory, as indicated by the fact that such animals have resisted a second challenge with the parental tumor cells. Induction of potent immune responses in tumor bearing animals against non-immunogenic tumors supports the view that active immunization of cancer patients deserves consideration despite lack of demonstrable immunogenicity in many human tumors.

Animals↗

Female fertility following extracorporeal shock wave lithotripsy of distal ureteral calculi.

This study was prompted by a spontaneous abortion in a 21-year-old woman following extracorporeal shock wave lithotripsy (ESWL ) of a distal ureteral calculus. To our knowledge, it is the first clinical retrospective study on the possible adverse effects of ESWL to the female reproductive tract. We analyzed treatment data and radiation exposure of 84 women in the reproductive period, and surveyed the patients by questionnaire, to which 67 (79.8%) responded. After ESWL 57 women (85.1%) practiced some form of contraception, while 10 childless women attempted to become pregnant. Overall 7 children with no malformations or chromosomal anomalies were born to 6 patients. Miscarriages were noted in 3 patients (4.5%) but they occurred at least 1 year after ESWL. Our data suggest that ESWL of lower ureteral calculi is a safe and effective procedure, and does not affect female fertility or lead to increased teratogenic risk.

Abortion, Spontaneous↗

Piroximone, dobutamine and nitroprusside: comparative effects on haemodynamics in patients with congestive heart failure.

Four intravenous doses of piroximone, an imidazolone derivative, were administered to 12 patients with congestive heart failure to produce a four-point dose-response curve. The haemodynamic effects were compared with those of dobutamine and nitroprusside, the substances being given sequentially and in randomized order. Piroximone and dobutamine significantly and similarly increased cardiac index (CI) and stroke volume index (SVI). Nitroprusside produced no such effect. By contrast, piroximone and nitroprusside significantly and similarly decreased mean pulmonary artery pressure (MPAP), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP) and pulmonary vascular resistance (PVR), while such changes were not seen following dobutamine. Direct comparisons between the agents were made at doses that lowered systemic vascular resistance (SVR) to the same extent. The major difference between dobutamine and piroximone was an apparent additional vasodilator activity displayed by piroximone as demonstrated by a significantly greater decrease in MPAP, PCWP and RAP for a matched reduction in SVR and a similar increase in CI. The major difference between nitroprusside and piroximone was the significantly higher increase in CI and SVI elicited by piroximone for a matched reduction in SVR and a similar decrease in PCWP and RAP. The changes in loading conditions being equivalent, the higher increase in CI is likely to be accounted for by a direct inotropic activity.

Adult↗

[Primary management of fresh injuries of the thoracic and lumbar vertebrae].

Results of conservative treatment of vertebral body fractures and of repositioning and internal fixation, are compared with those obtained by dorsoventral repositioning and fusion. The results achieved with patients treated by dorsoventral fusion were statistically significantly better than those obtained with the other two treatment methods. Consequently, we modified the treatment concept of thoracic and lumbar vertebral body fractures. Every vertebral disk showing irreversible damage is now resected and the mobility segment involved is fused. The fracture is treated conservatively only in case MR does not reveal any lesion of the vertebral disk, or it is stabilised only from the dorsal approach.

Adult↗

[Intra- and postoperative morbidity of radical prostatectomy].

Operation-related morbidity was analyzed in 147 patients, who had undergone radical prostatectomy during the last 3 years. Six major complications (4.1%) had occurred requiring surgical revision. One single postoperative death (0.7%) was caused by a pulmonary embolus. In 51 patients (34.7%) minor complications were noted. Urinary incontinence was severe in 4 patients (3.9%), which was treated by an artificial sphincter in one man during the follow-up period. Twelve patients (11.8%) complained of stress incontinence, grade I-II. Postoperative determinations of serum PSA were below the detectable range in 81% of the patients, including those with a locally advanced tumor stage and adjuvant antiandrogen therapy. Based on our data, it is concluded that radical prostatectomy is today a safe and standardized operative procedure.

Aged↗

[Validity of nuclear magnetic resonance tomography in evaluation of the traumatized intervertebral disk].

The validity of the magnetic resonance imaging (MRI) in the diagnosis of injured intervertebral discs was examined by a prospective diagnostic study. The golden standard being intraoperative discography. The examinations were carried out on both intervertebral discs adjoining the fractured vertebral body. There were 27 patients with 54 injured discs. The sensitivity of the MRI as a noninvasive method is 96%, the specificity is 75%. These results comply with a validity of 88%.

Adolescent↗

[Post-ischemia normal function of living related kidney transplants after preservation with HTK solution].

This study reports on the first clinical use of HTK preservation solution devised by Bretschneider in renal transplantation. Using this HTK solution, nine living related donor kidneys subjected to cold ischemia for up to 4 h were consecutively transplanted between 1987 and 1989. The postoperative function of the donor and recipient kidneys is analyzed. The endogenous creatinine clearance and the plasma creatinine level are used as function parameters. Within 24-48 h after transplantation a postischemic normal graft function occurred. With triple drug therapy the transplanted kidneys showed an increase in renal function identical with that in the donor's single remaining kidney. Within 7 postoperative days no perfusion damage and no HTK or CyA nephrotoxicity was observed.

Adult↗

Interobserver variability in the interpretation of unenhanced helical CT for the diagnosis of ureteral stone disease.

PURPOSE: The purpose of this study was to analyze interobserver agreement in the interpretation of unenhanced helical CT (UHCT) for the evaluation of ureteral stone disease and obstruction. METHOD: One hundred three UHCT examinations were independently and retrospectively reviewed by five readers including attending radiologists, a radiology resident, and an attending urologist. Examinations were interpreted as positive, negative, or indeterminate for ureteral stone disease and obstruction. The Cohen kappa test was used to measure interobserver agreement. The accuracy of the readers was also assessed. RESULTS: The kappa value ranged from 0.67 to 0.71 among the three attending radiologists and from 0.65 to 0.67 among the radiology attending physicians and radiology resident. Although the urologist tended to agree less well with the other readers (kappa range: 0.33-0.46), there was no statistically significant difference (p < 0.05) in the accuracy among all five readers. The percentage of cases interpreted as indeterminate ranged from 8 to 25% and almost invariably involved difficulty distinguishing phleboliths from minimally obstructing distal ureteral calculi. The percentage of UHCT scans correctly interpreted as positive and correctly interpreted as negative ranged from 73% (n = 27) to 86% (n = 32) and 63% (n = 22) to 86% (n = 30), respectively. CONCLUSION: Interobserver agreement was very good among the radiology attending physicians and resident and moderate with the urologist. The examination is an accurate technique in the evaluation of ureteral stone disease, although limitations exist, particularly in the diagnosis of minimally obstructing distal ureteral calculi.

Abdominal Pain↗