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M Krainer

Publications and source records attributed to M Krainer.

36 records · Page 2Linked to original sources
PubMed1996

Physical map and cosmid contig encompassing a new interstitial deletion of the X-linked lymphoproliferative syndrome region.

The X-linked lymphoproliferative syndrome (XLP) is an inherited immuno-deficiency to Epstein-Barr virus infection that has been mapped to chromosome Xq25. Molecular analysis of XLP patients from ten different families identified a small interstitial constitutional deletion in 1 patient (XLP-D). This deletion, initially defined by a single marker, DF83, known to map to interval Xq24-q26.1, is nested within a previously reported and much larger deletion in another XLP patient (XLP-739). A cosmid minilibrary was constructed from a single mega-YAC and used to establish a contig encompassing the whole XLP-D deletion and a portion of the XLP-739 deletion. Based on this contig, the size of the XLP-D deletion can be estimated at 130 kb. The identification of this minimal deletion, within which at least a portion of the XLP gene is likely to reside, should greatly facilitate efforts in isolating the gene.

Adolescent↗
PubMed1995

Natural killer cell activity in long-term survivors of testicular cancer. Influence of cytostatic therapy and initial stage of disease.

BACKGROUND: Patients with testicular cancer can be cured by cisplatin-based chemotherapy in many cases. Thus, concern about possible late toxicities of treatment is warranted. METHODS: In this investigation, the absolute number of natural killer (NK) cells according to their CD56+ phenotype, NK cell activity, and antibody dependent cellular cytotoxicity (ADCC) were investigated in 29 patients with seminomas or nonseminomatous germ cell tumors (NSGCT) a median of 31 months (range, 5-73 months) after termination of chemotherapeutic treatment. RESULTS: No difference in the absolute number of NK cells, NK cell activity, and ADCC was found between patients with testicular cancer after either standard polychemotherapy consisting of bleomycin, etoposide, and cisplatin (BEP) or monotherapy with carboplatin and healthy control subjects. When patients were analyzed further using multivariate analysis, a significant (P < 0.05) detrimental influence of BEP polychemotherapy versus carboplatin monotherapy on NK cell activity was found. Moreover, NK cell activity also depended significantly (P < 0.05) on the time elapsed after chemotherapy was administered, but normalized with time. Because the absolute number of NK cells was not affected, is was assumed that polychemotherapy induced a functional defect. In a subanalysis of patients with NSGCTs, metastases at diagnosis resulted in a significant (p < 0.05) and persistent stimulation of NK cell activity but not of ADCC. CONCLUSION: Cytostatic chemotherapy in patients with testicular cancer did not lead to compromised lytic effector cell function as assessed by NK cell activity and ADCC. However, a short, time-dependent reduction was found that also depended on the intensity of chemotherapeutic treatment. This finding related to the observation of a long-lasting stimulus of NK cell activity by initial metastases in patients with NSGCTs.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1995

Reduced mitogenic stimulation of peripheral blood mononuclear cells as a prognostic parameter for the course of breast cancer: a prospective longitudinal study.

Immunosuppression has been often associated with the course of malignant diseases. In the present study, the proliferation of peripheral blood mononuclear cells (PBMCs) in response to mitogenic stimulation with phytohaemagglutinin (PHA) was assessed prospectively in 90 patients with stage I-III breast cancer. Whereas PHA-induced proliferation of PBMCs derived from patients with breast cancer preoperatively was significantly decreased when compared with data obtained in healthy control individuals (P < 0.001), the degree of the defect in PHA-induced proliferation of PBMCs depended upon the tumour burden as manifested by tumour size and axillary lymph node involvement (P < 0.003 in each case). PHA-induced proliferation of PBMCs dropped significantly in patients who received adjuvant chemotherapy consisting of cyclophosphamide, methotrexate and fluorouracil (CMF) after an observation period of 6 months (P < 0.01), but not in patients under adjuvant treatment with tamoxifen only. After an additional 6 months (i.e. 12 months after surgery), PHA-induced proliferation of PBMCs was similar in patients after adjuvant chemotherapy with CMF and in those receiving continued adjuvant tamoxifen treatment (P > 0.1), but in all patients still significantly decreased as compared with healthy controls (P < 0.001). When data obtained preoperatively and after 12 months were compared, it was found that out of 23 patients whose PBMCs had experienced a drop in their PHA-induced proliferation, 14 (61%) had developed metastatic disease within the subsequent 24 months (i.e. 36 months after surgery). In contrast, out of 59 patients whose PBMCs showed an increase in their PHA-induced proliferation within the first 12 months after surgery, only one (2%) presented with disease progression. We thus conclude that PHA-induced proliferation of PBMCs derived from patients with breast cancer depends upon the tumour load and is a good clinical predictor for the further course of the disease.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

In vivo administration of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor increases neutrophil oxidative burst activity.

The influence of CSF therapy on the superoxide (O2-) releasing capacity in response to N-formyl-methionyl-leucyl-phenylalanine (FMLP) of neutrophils from 32 patients with testicular cancer receiving high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) was assessed: 8 patients were treated as control group without CSF therapy, 12 patients received GM-CSF, and 12 patients received G-CSF. To monitor the kinetics of the respiratory burst, leukocytes were collected before initiation of chemotherapy and ABMT, during CSF administration on days 1 and 3 after leukocyte recovery, and 7 days after leukocyte recovery (controls) or 3 days after the end of CSF therapy. Neutrophils from patients who received GM-CSF showed a significantly higher superoxide anion release compared with control patients (p < 0.001). O2- production in these patients was higher than that achieved by in vitro preincubation of neutrophils from control patients. Increased burst activity was seen only during infusion of GM-CSF and returned to pretherapeutic values after the end of GM-CSF administration. A similar but less pronounced increase was seen in patients who received G-CSF. In vitro preincubation of neutrophils from the same patients with GM-CSF, G-CSF, or TNF showed that O2- production by neutrophils from patients receiving GM-CSF could not be further enhanced, whereas O2- production by neutrophils derived from patients receiving G-CSF could be further augmented by TNF but not by GM-CSF. Interestingly, neutrophils from patients treated with GM-CSF but not those with G-CSF therapy retained a higher response to in vitro stimulation with GM-CSF or TNF after the end of CSF administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Bone Marrow Transplantation↗
PubMed1995

Influence of in vivo administration of GM-CSF and G-CSF on monocyte cytotoxicity.

The influence of colony-stimulating factors (CSFs) on the monocyte functions of 32 patients with refractory testicular cancer receiving high-dose chemotherapy followed by autologous bone marrow transplantation (ABMT) was tested. Eight patients were treated as a control group without CSF therapy, 12 patients received recombinant human granulocyte-macrophage-CSF (rhGM-CSF), and 12 patients received recombinant human granulocyte-CSF (rhG-CSF). For the assessment of monocyte activation induced by CSF expression of major histocompatibility complex (MHC) class I and II antigens, production of tumor necrosis factor (TNF) and monocyte-mediated cytotoxicity against tumor cell targets were chosen. Monocytes from patients with GM-CSF therapy showed a significant increase in MHC class I and II antigen expression as compared to patients without CSF treatment (p < 0.001). A significant increase in the expression of MHC class I was seen in monocytes from patients under G-CSF treatment, whereas no change of class II antigens was noticed. Production of TNF and monocyte-mediated cytotoxicity against U937 tumor cells was significantly increased in monocytes derived from patients receiving GM-CSF, as compared to those from the control group, while no effect was detectable in monocytes from patients with G-CSF therapy. However, after in vitro stimulation with interferon-gamma (IFN-gamma), monocytes derived from GM-CSF as well as from G-CSF treated patients responded with a significantly higher TNF-production and cytotoxicity than monocytes from control patients.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1995

[The significance of adhesion molecules in oncology].

Adhesion molecules are membrane proteins responsible for the complex functions of cell adhesion and cellular recognition and are thus of importance in inflammatory as well as neoplastic diseases. Adhesion molecules seem to play a significant role at each level of the metastatic cascade, including the destruction of normal cell-cell as well as cell-substrate cohesion, the penetration of tumor cells into the vascular system and the further spread into distant organs. In this summary an overview of subtypes, structure and function of the major groups of adhesion molecules is given and their possible role in the development, propagation and metastatic spread of malignancies discussed. Cell adhesion and its defects may be of importance in the behaviour of tumor cells and their spread. A better understanding of their function and possible manipulation of their expression, e.g., by cytokines could provide new therapeutic approaches in clinical oncology.

Cell Adhesion↗
PubMed1995

Increase of bone marrow cellularity during erythropoietin treatment in myeloma.

Treatment of myeloma-associated chronic anemia with recombinant human erythropoietin (rHuEPO) has been shown to be successful in the majority of patients. We have morphometrically investigated bone marrow sections from the iliac crest of 20 anemic myeloma patients prior to rHuEPO therapy. The 15 responding patients were re-examined after three months and, if possible, after 6 and 12 months of treatment. Significant differences were found between responders and nonresponders prior to therapy. Nonresponders presented with a pronounced shift to the right in their erythroid bone marrow cell compartment and partly with higher serum levels of endogenous erythropoietin. During rHuEPO therapy, responders showed increases in all subsets of erythropoiesis and in the total amount of hemopoietic tissue. Response was accompanied by a marked drop of serum ferritin levels, a rise in serum levels of transferrin receptors and the emptying of bone marrow iron stores; the World Health Organization performance status improved. Responders tended to present with less advanced disease stages and better performance status and showed significantly longer survival times. Loss of responsiveness to rHuEPO was observed in one patient during the terminal stage of the disease. In conclusion, morphometric examination of bone marrow biopsies during the course of rHuEPO therapy showed that the response achieved in hemoglobin values was clearly mirrored in equivalent increments of the erythroid bone marrow cell compartment.

Aged↗
PubMed1994

Increased natural killer cell activity correlates with low or negative expression of the HER-2/neu oncogene in patients with breast cancer.

BACKGROUND: Increased expression of the HER-2/neu oncogene in breast cancer correlates with decreased estrogen receptor concentration and seems to be an important prognostic factor. The authors investigated whether there is a correlation between HER-2/neu expression and immunologic parameters representing tumor defense in patients with breast cancer. METHOD: A Western blot analysis was used to investigate HER-2/neu expression, whereas a chromium-release assay using the K562 cell line as target was used to measure natural killer (NK) cell activity. RESULTS: In patients with breast cancer, NK cell activity was significantly higher compared with patients with benign tumors (P = 0.006) or healthy control subjects (P = 0.002). Moreover, 23.3% of patients with breast cancer showed an overexpression of HER-2/neu protein. Within this group of patients, NK cell activity was significantly lower (45.6 +/- 16.1%) compared with the group with no HER-2/neu overexpression (57.3 +/- 11.0%). NK cell activity did not increase in patients with HER-2/neu overexpression. Thus, there was a statistically significant correlation of cytolytic effector cell function with HER-2/neu expression of the tumor (P = 0.003), and HER-2/neu overexpression correlated with a negative estrogen receptor status (P = 0.005). CONCLUSION: These data add further evidence to previous observations from the authors' laboratory that certain tumor characteristics may be associated with reactions of the host with breast cancer.

Breast↗
PubMed1994

[Germ cell tumors of the testis].

Testicular cancer is the most common malignancy in men aged 15 to 30 years. In the 1990s testicular cancer has become one of the most curable solid neoplasms, and it can serve as a paradigm for the multimodal treatment of solid malignancies, making even a metastasized cancer a curable disease. The dramatic improvements in survival have occurred as a result of the combination of effective diagnostic techniques, improvement in serum tumour markers, modification of surgical technique and, above all, the development of highly effective multidrug chemotherapeutic regimens based on cisplatin. In the 1990s overall survival for all stages of testicular cancer should be well above 80% and should approach 100% for patients with low stage disease. Important studies forming the basis for the most up to date multimodality treatment are reviewed in this article. Alternative strategies for salvage therapy in poor risk patients and those who failed to respond to treatment are discussed, as well as minimization of toxicity in low risk patients.

Chemotherapy, Adjuvant↗
PubMed1993

Erythropoietin treatment for chronic anemia of selected hematological malignancies and solid tumors.

BACKGROUND: Neoplasias, especially in their more advanced stages, are often associated with chronic anemia of malignancy which impairs the patient's physical ability and quality of life. PATIENTS AND METHODS: Forty-two patients with chronic anemia associated with hematological malignancies (18 multiple myelomas, 10 myelodysplastic syndromes) or solid tumors (9 breast cancers, 5 colon cancers) were treated with 150-300 units/kg rHuEPO for a median time period of 16 weeks. Response was defined as an increase of the initial hemoglobin level by at least 2 g/dl. RESULTS: The response rates for solid tumors were comparable (44.4% and 40% for breast cancer and colon cancer, respectively), whilst the response in patients with hematological malignancies depended strongly on the disease entity (77.8% for multiple myeloma, 10% for myelodysplastic syndrome). Pretreatment serum levels of endogenous erythropoietin (EPO) were significantly higher in non-responding patients than in responders. During rHuEPO therapy, EPO levels in non-responders increased even further, while they remained basically unchanged in responding patients. In responders, the WHO performance status before the start of rHuEPO therapy was more favorable and showed impressive improvement during the course of treatment. The median survival time of responders was 28.0 months as compared to only 9.2 months for non-responders. Clinical symptoms of anemia subsided or at least considerably improved under successful rHuEPO therapy. With the exception of occasional flu-like symptoms, no undesirable effects of rHuEPO treatment were observed. CONCLUSIONS: In conclusion, rHuEPO treatment corrected anemia of malignancy both in patients with hematologic disease and in those with solid tumors, but responsiveness varied considerably amongst the different disease entities.

Aged↗
PubMed1991

Predictive value of interleukin-6 and neopterin in patients with multiple myeloma.

Concentrations of interleukin-6 and neopterin were measured in sera from 44 patients with multiple myeloma. To judge the relative prognostic value of these analyses, other clinical and laboratory variables were concomitantly determined. The patients were followed up to 9 years, and the abilities of all variables to predict outcome were assessed. Both neopterin (P = 0.0008) and interleukin-6 (P = 0.033) were significantly higher in patients with higher stages of the disease. The correlation between interleukin-6 and neopterin was weak but significant (Spearman's rank correlation coefficient, 0.38; P = 0.019). By univariate survival analysis using the product-limit approach, both neopterin (P = 0.0001) and interleukin-6 (P = 0.025) were identified as significant predictors of survival. Multivariate survival analyses by the proportional hazards technique demonstrated that either stage and neopterin or neopterin and interleukin-6 are useful combinations of predictor variables. Thus, interleukin-6, which is supposed to influence progression of multiple myeloma in an autocrine or paracrine manner, failed to contribute to prediction if stage was included in a model. In contrast, neopterin remained significant in all multivariate models.

Aged↗
PubMedDate not supplied

Tissue expression and serum levels of HER-2/neu in patients with breast cancer.

We have analyzed serum levels of soluble HER-2/neu in 42 primary breast cancer patients prior to any therapy and studied the relationship between the overexpression and amplification of HER-2/neu in the primary tumor after surgical excision and data obtained by pathohistological staging. In addition, we have investigated the sera of 62 patients with stage IV breast cancer. Using an enzyme-linked immunosorbent assay, we observed elevated serum HER-2/neu levels in 6/42 (14.2%) preoperative patients. In 42.8% of the patients with HER-2/neu tumor expression/amplification serum levels were increased. In contrast, only 8.5% of the patients without HER-2/neu expression/amplification in the primary tumor presented with elevated serum levels. There was a significant correlation between serum concentrations of soluble HER-2/neu and tumor size (p < 0.0001) or axillary lymph node involvement (p < 0.0001). In patients with stage IV disease, 27 of 62 (43.5%) had elevated soluble HER-2/neu serum levels. A highly significant correlation between soluble HER-2/ neu and CA 15-3 (p < 0.002) was observed. The correlation of serum concentrations of HER-2/neu with estrogen and progesterone receptor status of the primary tumor was not significant in both groups. In conclusion, the measurement of serum HER-2/neu levels at diagnosis defines a small subgroup of breast cancer patients with a relatively advanced stage of disease. Its strong correlation with tumor load in patients with stage II disease and the high prevalence in patients with stage IV disease could make it a promising tool for the assessment of disease activity and biologic behavior in breast cancer.

Biomarkers, Tumor↗