Separation of superficial and cerebral hemodynamics using a single distance time-domain NIRS measurement.

In functional near-infrared spectroscopy (fNIRS) superficial hemodynamics can mask optical signals related to brain activity. We present a method to separate superficial and cerebral absorption changes based on the analysis of changes in moments of time-of-flight distributions and a two-layered model. The related sensitivity factors were calculated from individual optical properties.

The physiological origin of task-evoked systemic artefacts in functional near infrared spectroscopy.

A major methodological challenge of functional near-infrared spectroscopy (fNIRS) is its high sensitivity to haemodynamic fluctuations in the scalp. Superficial fluctuations contribute on the one hand to the physiological noise of fNIRS, impairing the signal-to-noise ratio, and may on the other hand be erroneously attributed to cerebral changes, leading to false positives in fNIRS experiments. Here we explore the localisation, time course and physiological origin of task-evoked superficial signals in fNIRS and present a method to separate them from cortical signals.

Low molecular thymic peptides improve the deficient immunocytotoxicity of mononuclear cells from tumor patients in vitro.

We studied, in vitro, the stimulating effects of a commercial preparation of low molecular thymic peptides (TP) on the immunocytotoxicity of peripheral blood lymphocytes and monocytes from patients with breast tumors, melanoma and colorectal tumors. On average, tumor patients showed a lower natural killer (NK), lymphokine (IL-2) activated killer (LAK) cell and basic tumoristatic activity of monocytes, compared with healthy donors. There was no correlation between the NK-cell number and the NK-cell activity of the tumor patients.

Bromelain proteases suppress growth, invasion and lung metastasis of B16F10 mouse melanoma cells.

The thiolprotease bromelain, isolated from pine apple stem, was suggested for use in adjuvant tumor therapy. This study examined the in vitro effects of crude bromelain, bromelain F9 and papain on B16F10 mouse melanoma cell lung colonization, in vitro cell proliferation, invasion through matrigel and CD44 expression. In vitro treatment of the melanoma cells with bromelain F9 and papain before i.

Effects of thymic peptides, in vitro, on the impaired immunocytotoxicity of peripheral blood mononuclear cells from tumor patients.

The effects of a thymic peptide preparation (TP) on the immunocytotoxicity and cytokine secretion of peripheral blood lymphocytes and monocytes from patients with colorectal tumors, breast tumors and melanoma were studied in vitro. On average, breast tumor and melanoma patients showed significantly lower natural killer (NK) cell activities than colorectal tumor patients and normal controls. In contrast, the generation of lymphokine (IL-2) activated killer (LAK) cells was found to be comparable within the different tumor diseases (24% cytotoxicity), but lower than in the group of normal controls.

Telomerase activity in bladder cancer, bladder washings and in urine.

With only a few exceptions, the ribonucleoprotein telomerase has been found in malignant, but not in benign tissues. Telomerase is thus a potentially new diagnostic marker. Carcinoma of the urinary bladder is the most frequent malignant tumor of the urinary tract and, after prostatic carcinoma, the second most common malignancy of the genitourinary system.

Fresh peripheral blood mononuclear cell preparations are a better starting material than bone marrow after cryopreservation for immunomagnetic harvesting of CD34(+) hematopoietic cells.

Immunomagnetic separation using anti-CD34 monoclonal antibodies and paramagnetic microspheres has been used to enrich hematopoietic stem cells from human bone marrow, whole cord blood, or mobilized peripheral blood mononuclear cell collections. This method has been reported to achieve high separation purity of CD34+ cells in small scale experiments with fresh material. The aim of the present study was to compare the efficacy of the CD34+ cell selection technique, when thawed bone marrow or fresh peripheral blood mononuclear cells were enriched.

Synergistic and antagonistic interactions between docetaxel and interferon-beta on growth of human breast cancer cells in vitro.

Docetaxel and interferon-beta (IFN-beta) were tested alone and in combination for their antiproliferative activity against the estradiol receptor (ER) positive MCF-7 and the ER negative MDA-MB231 breast cancer cell lines. Cell growth inhibition was determined after a 3 day incubation by the sulforhodamine B assay. The antiproliferative effects of the drug combinations were analysed using Berenbaum's hyperplane theorem to determine additive, synergistic and antagonistic effects.

Phase II pilot trial of preoperative high-dose chemotherapy in patients with malignant tumors of the upper gastrointestinal tract.

The purpose of this trial was to test feasibility and tolerability of a multimodality treatment approach for patients with tumors in the upper gastrointestinal tract (EC, esophageal cancer; JC, cancer of the gastro-esophageal junction; GC, gastric cancer) including preoperative chemotherapy with the EAP-protocol as induction and a consecutive high-dose-chemotherapy for responding patients. Sixteen patients with locally advanced tumors of the esophagus, the gastro-esophageal junction or the stomach were treated with two cycles of EAP-chemotherapy (etoposide, 3x120 mg/m(2); adriamycin, 2x20 mg/m(2); cisplatin, 2x40 mg/m(2)). Responding (cPR, cCR) patients were included into a high-dose MCVB-chemotherapy protocol (mitomycin, 10 mg/m(2); cisplatin, 4x40 mg/m(2); vepeside, 5x200 mg/m(2); BCNU 300 mg/m(2)) and subsequent rescue with peripheral blood stem cells (PBSC).

Selective suppression of nuclear retinoic acid receptor beta gene expression in human pancreatic carcinomas.

Retinoids restore normal cell growth and differentiation in malignant cells and are considered as potential therapeutic agents. Before using retinoids for the treatment of pancreatic cancer it is important to determine the expression of nuclear retinoid receptors, which mediate most actions of retinoids on gene expression in normal and malignant tissues. Digoxigenin-labeled antisense riboprobes of retinoic acid receptors (RARs) alpha, beta, and gamma, and retinoid X receptor (RXR) alpha were used for in situ hybridization to histological sections of-specimens from 24 human pancreatic carcinomas, 20 of which also contained adjacent normal tissue.

Generation of progenitor-cell precursors in long-term bone-marrow cultures after marrow purging with ether lipids.

Alkyl-lysophospholipid derivates (ALP) are currently being tested as bone marrow (BM) purging agents prior to autologous BM transplantation in different malignancies. We evaluated the toxicity of the ALP ET-18-OCH3 (ET-18; Edelfosine, 1-0-octadecyl-2-0-methyl-rac-glycero-3-phosphocholine) towards early hematopoietic precursors by testing progenitor regeneration of non-purged and ET-18-purged BM (75 mu g and 125 mu g ET-18/ml/2x10(7) BM cells) in autologous long-term bone marrow cultures (LTBMC) from 3 different patients in complete remission. LTBMC feeder layers were irradiated with 875 rad for complete elimination of hematopoietic progenitors and recharged with cryopreserved purged and non-purged BM.

Phase-I tolerability study of 5-methyltetrahydrofolate in combination with a 4-hour infusion of 5-Fluorouracil in cancer-patients.

5-methyltetrahydrofolate (MTHF) is a main serum metabolite of 5-formyltetrahydrofolate (folinic acid, FA), a standard agent for potentiation of the cytotoxic activity of 5-fluorouracil (5-FU). The clinical application of MTHF instead of FA as a precursor of the biologically active metabolite 5,10-methyltetrahydrofolate (mTHF) is based on favorable pharmacologic characteristics of MTHF described so far. In this phase I study 18 patients with advanced solid malignancies were treated with MTHF for 5 days at doses ranging from 100 to 500 mg/m(2)/day in combination with a fixed dose of 500 mg/m2/day 5-FU given as a 4-hour infusion.

The influence of the thymic preparation thymex-L on deficient antitumor-activity of monocytes from melanoma patients in-vitro.

Recently we demonstrated that, in vitro, prothymosin alpha 1 (ProT alpha), a polypeptide from calf thymus, was able to enhance the deranged tumoristatic activity of peripheral blood monocytes from melanoma patients. Now we report, that the thymic preparation Thymex-L significantly enhanced the level of depressed monocyte activity from 19% to 26%, whereas in normal donor groups no significant change of basal activity (35%) was seen. Although the improvement of median levels of killer cell activity was found to be independent from the disease stage, the Thymex-L effect was only statistically significant in stage I and melanoma patients after chemotherapy.

Enhanced kinase-activity in sv40-transformed cells may be compensated by enhanced phosphatase-activity in revertants as reflected by phosphorylation of p53.

Transformation of rat cells with SV40 large T antigen results in activation of protein kinases and hyperphosphorylation of the tumor suppressor protein p53. In searching for cellular targets involved in SV40-mediated transformation, flat revertants of SV40-transformed rat cells had been isolated carrying a presumptive defect in a cellular gene (Bauer et al: J Virol 61: 1821, 1987). In this investigation, we asked whether the phosphorylation state of p53 might be affected in the revertants.

Bromelain proteinases modulate the cd44 expression on human molt-4/8 leukemia and sk-mel-28 melanoma-cells in-vitro.

CD44 cell surface proteins are involved in leukocyte binding to endothelium and the metastatic spread of tumor cells. Using flow cytometric analysis (FCMA), we investigated the effects of the proteases bromelain, papain, trypsin, and chymotrypsin on the density of CD44 molecules present on human leukemia Molt 4/8 cells. Bromelain was found to be most active in reducing CD44 receptor density.

Interleukin-1 receptor antagonist inhibits growth modulation of human tumor-cell lines by interleukin-1 in-vitro.

In this study we report that recombinant human (rh) interleukin-1alpha (IL-1alpha) has direct and dose-dependent growth-modulating effects on human tumor cell lines in vitro as measured by a human tumor cloning assay (HTCA). Colony formation of the melanoma cell line A 375 was inhibited by rhIL-1alpha, whereas colony formation of the glioblastoma cell line HTB 14 was enhanced by this cytokine. Both growth-modulating effects were dose-dependent, however with some saturation.

Macrophage inflammatory protein (mip)-1-alpha stem-cell inhibitor (sci) does not affect clonal growth of human solid tumor-cell lines in-vitro.

MIP-1alpha is a member of a family of proinflammatory cytokines produced by activated macrophages which has been shown to be a negative regulator of early hematopoietic stem cell progenitors. We report on results testing recombinant human (rh) MIP-1alpha on the clonal growth of different human nonhematopoietic tumor cell lines in vitro. Cell lines tested included the following histologies: 7 glioblastomas, 1 neuroblastoma, 2 head and neck carcinomas, 4 lung carcinomas, 3 colorectal carcinomas, 1 gastric carcinoma, 1 pancreatic carcinoma, 1 breast carcinoma, 1 prostate carcinoma, 1 choriocarcinoma, 1 ovary carcinoma, 1 osteosarcoma, and 3 melanomas.

Recombinant human granulocyte-colony-stimulating factor (rhg-csf) does not stimulate in-vivo tumor-growth of the human colon-cancer cell-line htb 38 which is responsive in-vitro.

Haematopoietic growth factors such as human granulocyte colony-stimulating factor (G-CSF) have been shown to stimulate in vitro growth of some human solid tumour cell lines. Among these is the human colorectal adenocarcinoma cell line HTB 38. The in vivo relevance of this finding was tested by xenografting HTB 38 cells intracutaneously into athymic nu/nu BALB/c mice.

Interleukin-4 inhibits growth of a human lung-tumor cell-line in-vitro and has therapeutic activity against xenografts of this cell-line in-vivo.

In the present study we report that recombinant human (rh) interleukin 4 (IL-4) has direct, dose-dependent antiproliferative effects on the human lung cancer cell line CCL 185 in vitro as measured by a human tumor cloning assay (HTCA). The biological response of the tumor cells to rhIL-4 is correlated with expression of specific binding sites for human (h) IL-4 on the cell surface. Furthermore, we have xenotransplanted CCL 185 into BALB/c nu/nu mice.

A semiautomatic microassay to measure human tumor clonogenic growth-invitro.

A semi-automatic micromethod was developed using 96-well microtiter plates in combination with a video monitoring system to assay human tumor clonogenic growth in vitro. The conditions to follow the growth of K562 human myeloid colonies were optimized and validated: About 250 cells in a 40 mul agar mixture are to be seeded per well. The colony number is proportional to the number of seeded cells.

Mutation and expression of the p53 tumor suppressor gene in tumor samples and cancer cell-lines - comparison of nonisotopic direct DNA-sequencing, immunoblotting and immunohistochemistry.

Mutations in the nuclear phosphoprotein p53 are the most frequent genetic alterations in human solid tumors detected so far. These mutations are clustered in highly conserved domains spanning from exon 4 to 9 of the gene. A very precise method of detecting p53 mutations is to sequence these domains.

Bomirski melanomas - a versatile and powerful model for pigment cell and melanoma research (review).

Models of animal melanoma are still indispensable tools in oncological research because they can be studied in syngeneic hosts while human melanomas cannot. One such model is a family of melanomas which originated in 1959 from a spontaneous melanotic melanoma of the skin in Syrian hamster, the Bomirski melanomas. Currently, it consists of 5 transplantable in vivo-variants (Ma, Ab, MI, MI-B and Ab455) and several cell lines derived from Ab amelanotic and Ma melanotic tumors.