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K Höffken

Publications and source records attributed to K Höffken.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1994

Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma. German Cancer Aid 17-1A Study Group.

Over the past decade various clinical trials have used monoclonal antibodies as therapeutic agents against solid tumours. No consistent pattern of response or improved survival has yet emerged although antigenic heterogeneity and insufficient accessibility of cells in advanced tumours have been offered as explanations for these failures. We designed a study in which a monoclonal antibody was used to target minimal residual disease in an early stage of tumour cell dissemination in patients with colorectal cancer. Only patients in Dukes' stage C who had undergone curative surgery and were free of manifest residual tumour were admitted. 189 patients with colorectal cancer of stage Dukes' C were randomly assigned to an observation regimen or to postoperative treatment with 500 mg of 17-1A antibody, followed by four 100 mg infusions each month. A balance of risk factors in the two groups was achieved by dynamic randomisation procedure. After a median follow-up of 5 years, antibody treatment reduced the overall death rate by 30% (Cox's proportional hazard, p = 0.04, log-rank p = 0.05) and decreased the recurrence rate by 27% (p = 0.03, p = 0.05). The effect of antibody was most pronounced in patients who had distant metastasis as first sign of a relapse (p = 0.0014, p = 0.002), an effect that was not seen for local relapses (p = 0.74, p = 0.67). Toxic effects of 17-1A antibody were infrequent, consisting mainly of mild constitutional and gastrointestinal symptoms. During 371 infusions four anaphylactic reactions were seen, all controllable by intravenous steroids and none necessitated admission to hospital. Adjuvant therapy with 17-1A antibody extends life and prolongs remission in patients with colorectal cancer of Dukes' stage C.

Antibodies, Monoclonal↗
PubMed1994

Serum cytokine levels in cancer patients treated with different schedules of ultra-low-dose interleukin-2.

Interleukin-2 (IL-2) induces secondary cytokines in vivo that may mediate antitumor effects as well as toxicity. The course and quantity of this in vivo reaction may depend on scheduling of IL-2 due to changes in responsiveness of the respective producer cells. This was evaluated in a phase-Ib study with ultra-low-dose IL-2 at 0.9 and 4.5 MIU/m2 administered once daily subcutaneously either once weekly (4 doses, stratum I), three times a week every other day (9 doses, stratum II), or five times a week every other week (10 doses, stratum III). Twenty-eight patients with advanced cancer were randomly assigned to the six treatment groups. Serum levels of IL-2, secondary cytokines, and soluble receptors were significantly increased after a single dose of 0.9 MIU/m2 s.c. demonstrating systemic efficacy. Baseline levels and native responsiveness were recovered after a 1-week treatment-free interval in stratum I patients with the exception of sCD8 that was still increased although readily inducible at that time. Stratum II patients exhibited a prolonged and possibly continuous elevation of all serum parameters studied. Values did not increase beyond the 2nd week of therapy and even decreased with respect to sCD8 and neopterin. A sequential mode of administration (stratum III) may obviate some of these adaptive mechanisms as evidenced from a progressive increase of neopterin and sCD8 levels after the second treatment cycle, although induction of sTNFRI was saturable under these conditions. Thus, scheduling of IL-2 profoundly affects in vivo responses as evidenced from cytokine and soluble receptor serum levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

Formestane in the treatment of advanced postmenopausal breast cancer.

In a phase II study, 91 women with advanced breast cancer received formestane (Lentaron) 500 mg intramuscularly every 2 weeks for 6 weeks, and then 250 mg every 2 weeks thereafter; all were either postmenopausal or surgically oophorectomized, and most had received previous hormonal treatment and/or chemotherapy. Complete or partial response was seen in 23%, disease stabilization in 29%. Disease-free interval and site of metastatic lesions did not significantly affect response. Patients who had previously responded to tamoxifen showed the best results with formestane. Side effects were generally mild and transient; only 3 patients had to discontinue treatment. Serum estradiol and estrone levels fell significantly after 2 weeks' treatment, and remained suppressed; there were no significant changes in serum cortisol, blood parameters, and liver and kidney function. Formestane thus appears to be an effective, specific and well-tolerated aromatase inhibitor for the treatment of advanced postmenopausal breast cancer.

Adult↗
PubMed1993

[Granulocyte function in myelodysplastic syndrome before and after low-dose cytarabine therapy].

Granulocytic phagocytosis ability (phagocytosis index in peripheral blood and in skin chamber exudate) and in vivo chemotaxis (skin chamber leukocyte mobilisation) were investigated in 22 patients with myelodysplastic syndrome (19 men, three women, mean age 66.1 [46-82] years). The control group consisted of 20 young, healthy subjects (13 men, seven women, mean age 25 [22-27] years). The studies were repeated in twelve of the patients after 10 days of low-dose cytarabine therapy (10 mg twice daily subcutaneously). Before treatment, total leukocyte mobilisation (TLM) after 24 hours (3.43 +/- 0.6 G/l.cm2) and phagocytosis index (PI(blood): 33.9 +/- 16.6%, PI(skin) chamber: 34.1 +/- 13.1%) were significantly lower (P < 0.05) than in controls (TLM: 6.7 +/- 0.78 G/l.cm2, PI(blood): 59.6 +/- 17.8%, PI(skin) chamber: 37.4 +/- 18.1%). Following treatment for 10 days, the values were still depressed or had even worsened (TLM: 3.09 +/- 0.97 G/l.cm2; PI(blood): 35.6 +/- 24.1%, PI(skin) chamber: 19.9 +/- 8.6%; all P < 0.05). Investigation of granulocytic function in myelodysplastic syndrome may reveal evidence of reduced immune protection by these cells against infection. Low-dose cytarabine therapy does not seem to affect cell differentiation.

Aged↗
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

Immunomodulatory effects of ultra-low-dose interleukin-2 in cancer patients: a phase-IB study.

High-dose interleukin-(IL-2) has been broadly studied in tumor therapy, yet it may be inhibitory to T-cell-dependent immunity. Therefore immune and tumour responses mediated by low-dose IL-2 were studied systematically with respect to the feedback organisation of immune responses. IL-2 was administered once daily at three dose levels: 0.18, 0.9, 4.5 MIU/m2 according to three different schedules requiring subcutaneous (s.c.) injection once weekly (four doses, stratum I), thrice weekly every other day (nine doses, stratum II), or five times weekly every other week (ten doses, stratum III). A total of 46 patients with advanced cancer were randomly assigned to one of the nine treatment groups. Systemic effects were induced at doses as low as 0.18 MIU/m2 IL-2 s.c. as demonstrated from measurable IL-2 serum levels, induction of circulating IL-6, a transient lymphopenia, and stimulation of delayed-type hypersensitivity (DTH) responses of the skin. Analysis of the different IL-2 schedules demonstrated (a) prolonged effects of once-weekly injections on DTH responses, lymphocyte and eosinophil counts, and (b) maximum increase of eosinophil counts and preferential expansion of activated NK cells with repeated injections every 48 h or 72 h (stratum II), while sequential treatment according to stratum III was found to be more potent in increasing the number of activated T cells. A tumour response was observed in 1/15 patients with renal cell carcinoma who experienced more than 50% tumour regression for 8 months; 12 patients had stable disease for 4 months (median). These data demonstrate prolonged immunological effects of ultra-low doses of s.c. IL-2 despite its short half-life. Furthermore, scheduling of IL-2 was found to affect immune responsiveness specifically as demonstrated by the differential effects on natural killer and T cell populations.

Adult↗
PubMed1993

Experience with aromatase inhibitors in the treatment of advanced breast cancer.

Inhibition of the aromatase enzyme system has become an established means of hormonal treatment for hormone-responsive advanced breast cancer. The widest clinical experience is with aminoglutethimide, which achieves around 30% objective remissions of metastatic disease for up to 1 year. Due to the sometimes serious side-effects of this drug, preclinical and clinical investigations have been undertaken and have yielded a number of steroidal and non-steroidal aromatase inhibitors that have been shown in early or mature clinical trials to give objective disease remissions similar to those with aminoglutethimide but with less toxicity. There is thus good reason to believe that newer aromatase inhibiting drugs will soon be available for routine use in patients with breast cancer. This paper summarizes our experience and reviews data from other groups.

Aminoglutethimide↗
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↗