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R Kath

Publications and source records attributed to R Kath.

At least 19 recordsLinked to original sources
PubMed1998

Pharmacoeconomic evaluation of high-dose chemotherapy and peripheral blood stem cell support in high-risk or poor-prognosis malignancies.

Discussion of the total costs and cost-effectiveness ratios of patients receiving high-dose chemotherapy (HDC) and peripheral blood stem cell support (PBSCS) is controversial. In Germany, no reliable data are available, whereas in other countries this issue has been extensively studied. We performed a pharmacoeconomic evaluation on all patients (n = 37) treated with HDC and PBSCS at our institution between July 1994 and June 1997. Patients suffered from high-risk or poor-prognosis breast cancer (n = 24), Hodgkin's disease (n = 3), high-grade non-Hodgkin's lymphoma (n = 4), multiple myeloma (n = 2), small-cell cervical cancer (n = 1), malignant hystiocytosis (n = 1) and testicular cancer (n = 2). For pharmacoeconomic evaluation, the period from initiation of induction chemotherapy (IC) until reconstitution after the last course of HDC and PBSCS was considered. A total of 18 patients received IC/HDC/PBSCS for locally advanced or systemic disease, and 19 patients received adjuvant or consolidation IC/HDC/PBSCS. Treatment protocols were heterogeneous. Patients were treated with two to five courses (median two) respectively of IC and sequential mono-HDC (n = 26), tandem-HDC (n = 10) or triple-HDC (n = 1). All patients received granulocyte/macrophage-colony-stimulating factor (G-CSF) for stem cell mobilisation and for amelioration of neutropenia after HDC. The relative costs (based on supplier prices) for the total amount of drugs prescribed during the in-patient period was 29.8% for G-CSF, 35.8% for blood products 18.5% for chemotherapy, 2.4% for antiemetics, 5.9% for antimicrobial drugs and 7.6% for other drugs. Contrary to expectations, antimicrobial drugs had only a minor pharmacoeconomic impact during IC/HDC/PBSCS in patients with high-risk or poor-prognosis malignancies, indicating that prolonged septic complications were uncommon in our institution. We conclude that pharmacoeconomic evaluations in IC/ HDC/PBSCS might be integrated into the effort to ensure quality control and monitoring.

Antineoplastic Agents↗
PubMed1997

[High dose chemotherapy of solid tumors].

BACKGROUND: The availability of hemopoetic growth factors and the retransfusion of autologous peripheral blood stem cells (PBSC) have enabled high-dose chemotherapy (HDT) options for the treatment of advanced solid tumours, during recent years. Though the transfusion of PBSC can manage the myelosuppression, dose-escalation ist still limited by non-haematological toxicity. METHOD: Usually, HDT has been given after a proceeding dose-intense chemotherapy that allowed the evaluation of chemosensitivity of the disease and resulted in a stem cell mobilization into the peripheral blood. The autologous bone marrow transplantation has almost completely been replaced by retransfusion of PBSC together with hemopoietic growth factors as specific supportive treatment. The PBSC are harvested by apheresis using a blood cell separator. RESULTS: Results on the efficacy of HDT are available for breast, testicular, ovarian, small cell lung cancer as well as melanoma, glioblastoma and soft-tissue sarcoma. The studies showed the feasibility and efficacy of HDT with tolerable toxicity. CONCLUSION: High-dose chemotherapy will be of increasing importance in the treatment strategies of primary solid tumors, in the near future.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

BRCA1 mutations and phenotype.

More than 100 mutations have been described for the breast-cancer-susceptibility gene BRCA1. The paper describes phenotypical aspects of three selected mutations located at the beginning, in the middle, and at the end of the gene. A remarkable decrease of the age of diagnosis of the mammary carcinoma is observed with increasing length of the putative gene product, combined with greater severity of the disease.

Adult↗
PubMed1996

BRCA1 mutations in German breast-cancer families.

We analyzed germline mutations of the BRCA1 gene in 20 German breast/ovarian-cancer families. BRCA1 mutations co-segregating with breast-cancer susceptibility were identified in 3 of these families. All mutations were found to generate a premature stop codon leading to the synthesis of truncated BRCA1 proteins of different length. Nine polymorphisms were detected in BRCA1, 4 of which have not been described previously. Analysis of familial tumors for LOH revealed that only the disease-related allele of BRCA1 was present.

Adult↗
PubMed1996

The neu oncogene product in serum and tissue of patients with metastatic gastrointestinal carcinomas.

We report on our experience investigating the serum levels of the soluble domain of p185 and the neu protein expression in the corresponding tumour tissue in patients with advanced gastrointestinal carcinomas. The study included 32 patients who were treated with palliative chemotherapy. The serum levels of the neu protein were investigated by immunosorbent assay techniques. We used the alkaline phosphatase/anti-(alkaline phosphatase) method for investigating the corresponding tumour tissue immunohistochemically. Increased serum neu protein levels were found in 8 of 22 (36%) patients with colorectal carcinomas and in 2 patients with advanced abdominal adenocarcinoma of unknown primary. All other patients with advanced gastrointestinal cancers were serum-neu-protein-negative. All serum-neu-protein-positive patients with colorectal carcinomas showed also an elevated neu protein expression. The extent of serum neu protein expression corresponded to the clinical course and the tumour marker CA 19-9. The serum neu protein may be useful for monitoring patients with advanced colorectal carcinomas, particularly in cases of immunohistochemical neu-protein-positive primary tumours.

Adult↗
PubMed1996

[Cytokines].

Explore the source record for details and available documents.

Animals↗
PubMed1995

Primary gastric non-Hodgkin's lymphoma: a clinicopathological study of 41 patients.

Pathological findings in 41 patients (male/female ratio: 1.3/1) with primary localized gastric non-Hodgkin's lymphoma (NHL) were retrospectively studied and correlated with survival. The median observation period after diagnosis was 32 (0-189) months. Nineteen patients were low-grade NHL, all but one B-cell lymphomas of the mucosa-associated lymphoid tissue (MALT) type. Twenty-two patients had primary (n = 7) or secondary (n = 15) high-grade lymphomas; Musshoff stage IE was found in 29 and IIE in 12 cases. The median age at diagnosis was 61 years (range, 26-88 years), and proliferation, measured by the number of mitosis and Ki-67 antigen positivity (MIB-1), was high or moderately high in 24 cases and low in 17 cases. Follicular lymphatic hyperplasia could be found in 25 of 34 evaluable cases, more often in low-grade than in high-grade NHL. Most of the patients were treated by resective surgery and additional ratio- or chemotherapy. Thirteen patients (31%) died (median survival: 10 months), 5 of them within 3 months after surgery owing to postoperative complications. Survival was superior, though not statistically significant, in low-grade lymphomas. Our retrospective analysis of heterogeneously treated gastric lymphomas reveals that gastric lymphomas, especially of the low-grade MALT type, often remain a localized disease with a good long-term prognosis. Our study confirms previous reports indicating that lymphomas of the MALT type represent a specific clinicopathological entity.

Adult↗
PubMed1993

Prognosis and treatment of disseminated uveal melanoma.

BACKGROUND: The clinical course of uveal melanoma differs greatly from that of cutaneous melanoma. METHODS: Twenty-four patients with metastatic uveal melanoma (13 men and 11 women; median age at diagnosis, 56 years [range, 17-67 years]) were evaluated retrospectively. RESULTS: Main sites of metastases were liver (87%), lung (46%), bone (29%), and skin (17%). Median relapse-free survival time was 36 months (range, 5-240 months). Median survival time after clinical detection of metastases was 9 months (range, 1-54 months). Relapse-free survival time was significantly greater in patients 50 years of age or younger. After manifestation of metastases, the clinical course was more favorable in patients in whom the liver was either not involved at all or not among the first sites of dissemination. These patients had a median survival time of 19 months, compared with 7 months for patients in whom the liver was involved initially. First-line systemic treatment of metastatic disease yielded three cases of stable disease lasting 6-14 months, but no complete or partial response. Three patients received intraarterial liver perfusion as first- or second-line treatment, resulting in one partial response, which lasted 6 months. CONCLUSION: Treatment and prognosis results of patients with metastatic uveal melanoma were poor, especially when the disseminated to the liver; survival time of approximately 9 months can be expected.

Adolescent↗
PubMed1993

The neu-oncogene product in serum and tissue of patients with breast carcinoma.

BACKGROUND: A soluble 105 kD neu-related protein is detectable in conditioned medium from breast cancer cells expressing the neu-oncogene product and in serum of nude mice bearing tumors that overexpress neu-oncogene. PATIENTS AND METHODS: In 100 patients with primary (n = 33) relapse-free (n = 6) and metastatic (n = 61) breast carcinoma the serum levels of the soluble neu-related protein were investigated by ELISA techniques. Median age was 57 years, range 26-89 years. RESULTS: The neu-protein serum levels were below 40 HNU/ml (human neu-antigen unit) in 72 patients and 40 or more HNU/ml in 28 patients. In 30 patients with primary breast carcinoma, tested before mastectomy, all serum-neu-protein samples were negative. However, 26 of 61 metastasized patients (43%) were serum-neu-protein-positivity. In disseminated disease (n = 61), serum-neu-protein-positivity was more likely to be seen in patients with visceral metastases (18/33 = 54%), than in patients with nonvisceral metastases (8/28 = 28%). Furthermore, monitoring of the serum-neu-protein levels reflected clinical course. For 53 patients original paraffin-embedded tumor material was available for studying immunohistochemical neu-protein expression. In 39/53 (73%) patients immunohistochemical and ELISA data showed corresponding results. In 27/30 (90%) patients, from whom sera and tissue could be obtained at the same time at primary mastectomy, results of immunohistochemistry in primary tumor and serum ELISA were negative and mutually confirmatory. However, the other three patients were positive for immunohistochemical neu-protein expression in primary tumor but negative for serum-neu-protein expression. CONCLUSIONS: Our results suggest that patients with advanced breast cancer and an elevated serum-neu-protein level may have a poor clinical outcome. This test might be a useful tool for monitoring patients with advanced breast carcinoma, but not those with early disease. Further prospective studies are warranted to elucidate the question of whether this test can contribute to determining prognosis and treatment strategies.

Adult↗
PubMed1992

Treatment of high-risk, nonseminomatous testicular cancer with cisplatin, ifosfamide and bleomycin: long-term results.

Thirty-four patients with stage IIC (unresectable, retroperitoneal tumor mass (RTM) greater than 5 cm), stage IVC (minimal lung metastases less than 10 cm3 and RTM greater than 5 cm) and IVD (lung metastases greater than 10 cm3 and RTM greater than 5 cm), who had not received previous chemotherapy, were treated with cisplatin (40 mg/m2, on days 2-4), ifosfamide (5 g/m2, on days 1 and 5) and bleomycin (30 mg, on days 1, 8, 15) (PIB), every 21 days. Twenty of the 34 patients (59%) achieved a complete remission (CR). Furthermore, five patients (15%) showed no evidence of disease (NED) after surgical removal of residual tumor masses (NED rate of 74%). A tumor marker-negative partial remission (PR) occurred in 3/34 patients (9%), and a tumor marker-positive PR in another 3/34 patients (9%). Three patients did not respond to this regimen. At a median follow-up period of 38 months (range, 15-47 months), 26/34 patients (76%) were alive, 21 (62%) of them without evidence of disease and three with a stable tumor marker-negative remission. Major toxicity consisted of myelosuppression, neurotoxicity and nephrotoxicity. Chemotherapy-related mortality occurred in two patients (one septicemia and one bleomycin-induced lung fibrosis). In conclusion, PIB is an effective induction regimen in patients with high-risk NSTC. However, controlled clinical trials are necessary to prove the superiority of dose intensification schedules.

Adult↗
PubMed1991

Characterization of tenascin secreted by human melanoma cells.

Tenascin is a large glycoprotein of the extracellular matrix. It shows a site-restricted expression during embryogenesis and can be found in adult tissues during wound healing and tumorigenesis. Because of the potential involvement of tenascin in adhesion and invasion during metastasis, the study of the interactions of tumor cells with tenascin is of considerable interest. Using five anti-melanoma monoclonal antibodies to four different epitopes of human tenascin, we found that most melanoma cells secrete tenascin in vitro constitutively. Transforming growth factor beta 1 in the medium increased secretion in tenascin-producing cells. Tenascin was present in sera of melanoma patients, with significantly elevated levels in patients with advanced melanomas as compared to patients with low tumor burden or to normal donors. Normal and malignant melanocytes did not attach to tenascin as substrate within 1 to 2 h and tenascin could also inhibit fibronectin-dependent adhesion. These results indicate that tenascin may play a critical role in cell-substrate interactions of melanoma cells.

Antibodies, Monoclonal↗
PubMed1991

Development of invasive and growth factor-independent cell variants from primary human melanomas.

Growth autonomy and high levels of invasiveness are characteristics of human melanoma cells that are metastatic in vivo. By consecutive passage through a reconstructed basement membrane, we have selected from 5 of 6 primary melanoma cell lines variants which show an up to 10-fold increase in invasiveness. The invasive variants grew more rapidly than the parental, noninvasive cells in serum- and growth factor-free medium and one of the 3 variant cell lines with the highest invasive capacity in vitro metastasized to the lungs when injected s.c. into nude mice. In a second approach, variants of 6 primary melanoma cell lines were clonally selected in medium without exogenous growth factors (protein-free medium). These selected cells showed higher invasive properties in vitro and in vivo than the parental cells. Clones of invasive and growth factor-independent cell variants were heterogenous and changed over time in the absence of selected pressure to a phenotype similar to that of parental nonselected cells. These results indicate that primary melanoma cells contain subpopulations of cells that have the phenotype of an advanced (metastatic) stage of tumor progression, but this phenotype is not stable without selective pressure.

Growth Substances↗
PubMed1991

[The staging diagnosis of Hodgkin's disease. A comparison of laparotomy and noninvasive methods].

The diagnostic efficiency of modern noninvasive methods more and more puts into question the need for exploratory laparotomy to determine the stage of Hodgkin's disease. In 208 patients (122 men and 86 women; mean age 29 [14-62] years) pre- and postoperative findings as to stage of the abdominal disease were compared. All patients had first been examined by ultrasound and computed tomography, followed by laparotomy with splenectomy. Findings of lymphography were available for 171 patients. Gross and microscopic examination of the tissues obtained by splenectomy and lymphadenectomy, as well as liver biopsy provided different stages from the preoperative ones, which in 46 had been false-negative, and in 16 false-positive. Spleen weight and involvement of the spleen with Hodgkin infiltration correlated only weakly with one another. In 38 of 41 patients with parapancreatic and splenohilar lymphnode involvement the spleen was also affected. These results indicate that regarding the stage of Hodgkin's disease, noninvasive methods so far do not achieve the validity of pathological examination obtained at exploratory laparotomy with splenectomy.

Adolescent↗
PubMed1991

Constitutive expression of multiple growth factor genes by melanoma cells but not normal melanocytes.

In a panel of metastatic melanoma cell lines we found steady-state mRNA transcripts for multiple growth factors including basic fibroblast growth factor (bFGF), platelet-derived growth factor (PDGF)-A, PDGF-B, transforming growth factor (TGF)- beta 1, TGF- alpha, melanoma growth-stimulating activity (MGSA), interleukin (IL)-1 alpha, and IL-1 beta but not insulin-like growth factor (IGF)-1 or IGF-2. Expression of growth factor genes was constitutive because prior to RNA extraction melanoma cells were maintained in a chemically defined culture medium free of exogenous growth factors. Each of four cell lines had an individual pattern of expression of either two, four, five, or seven growth factors; however, all cell lines shared expression of the bFGF gene. Two strains of normal melanocytes expressed TGF- beta 1 but not bFGF, PDGF, TGF- alpha , or MGSA mRNA at detectable levels. We tested growth-modulatory effects of the growth factors most frequently expressed by melanoma cells (bFGF, TGF- alpha, TGF- beta, PDGF). None of these stimulated melanoma cell growth consistently, whereas exogenous, acid-activated TGF- beta inhibited melanoma growth at concentrations greater than 10 ng/ml, suggesting that bioactive TGF- beta may represent a physiologic growth inhibitor. Neither neutralizing antisera to PDGF or TGF- alpha nor a monoclonal antibody to the epidermal growth factor (EGF)-receptor inhibited melanoma cell growth. Our results indicate that multiple growth factors are expressed simultaneously and constitutively by melanoma cells but not normal melanocytes in culture. Expression of bFGF is a common feature underscoring the significance of bFGF as an autocrine factor for melanoma cells as described earlier. Secreted PDGF and TGF- alpha are apparently not involved in or not essential for autocrine growth stimulation of melanoma cells.

Blotting, Northern↗
PubMed1990

[Chemotherapy of nonendemic Burkitt's lymphoma].

14 patients (12 men, 2 women, mean age 26.3 [15-47] years) with histologically confirmed Burkitt's lymphoma were subjected between 1984 and 1989 to chemotherapy originally developed for treating lymphomas in children. Treatment consisted of medium doses of methotrexate, cyclophosphamide, teniposide, cytarabine, adriamycin and prednisone, intrathecal administration of methotrexate and if necessary prophylactic or therapeutic irradiation of the cranium. Most of the patients (64%) were in advanced stages of the disease. The rate of complete remissions was 100%. Four patients (29%) had a recurrence. Side effects were leukopenia (WHO grade III and IV) in 71%, grade III anaemia in 43% and grade III-IV thrombopenia in 29% of the patients. Considerable mucositides in 5 of the 14 patients (36%), and in one case a tumour lysis syndrome with transient renal insufficiency were other therapy-induced side effects. These results suggest that this treatment course can be successful also in non-endemic Burkitt's lymphoma in adolescents and adults.

Adolescent↗