An anti-glioblastoma gold(i)-NHC complex distorts mitochondrial morphology and bioenergetics to induce tumor growth inhibition.

Glioblastoma multiforme (GBM) is the most lethal brain cancer subtype, often advanced by the time of initial diagnosis. Existing treatment modalities including surgery, chemotherapy and radiation have been stymied by recurrence, metastasis, drug resistance and brain targetability. Here, we report a geometrically distinct Au(i) complex ligated by N^N-bidentate ligands and supported by a N-heterocyclic ligand that modulates mitochondrial morphology to inhibit GBM in vitro and in vivo. This work benefits from the facile preparation of anti-GBM Au(i)-NHC complexes.

Water-Soluble Gold(III)-Metformin Complex Alters Mitochondrial Bioenergetics in Breast Cancer Cells.

Chemical control of mitochondrial dynamics and bioenergetics can unravel fundamental biological mechanisms and therapeutics for several diseases including, diabetes and cancer. We synthesized stable, water-soluble gold(III) complexes (Auraformin) supported by biguanide metformin or phenylmetformin for efficacious inhibition of mitochondrial respiration. The new compounds were characterized following the reaction of [C N]-cyclometalated gold(III) compounds with respective biguanides. Auraformin is solution stable in a physiologically relevant environment. We show that auraformin decreases mitochondrial respiration efficiently in comparison to the clinically used metformin by 100-fold. The compound displays significant mitochondrial uptake and induces antiproliferative activity in the micromolar range. Our results shed light on the development of new scaffolds as improved inhibitors of mitochondrial respiration.

P300 from a single-stimulus paradigm: passive versus active tasks and stimulus modality.

The P300 component of the event-related brain potential (ERP) was elicited with auditory and visual stimuli in separate experiments. Each study compared an oddball paradigm that presented both target and standard stimuli with a single-stimulus paradigm that presented a target but no standard stimuli. Subjects were instructed in different conditions either to ignore the stimuli, press a response key to the target, or maintain a mental count of the targets. For the passive ignore conditions, P300 amplitude from the single-stimulus paradigm was larger than that from the oddball paradigm. For the active tasks, P300 amplitude from the oddball paradigm was larger than that from the single-stimulus paradigm. For the press and count conditions, P300 amplitude and latency were highly similar for the oddball and single-stimulus procedures. The findings suggest that the single-stimulus paradigm can provide reliable cognitive measures in clinical/applied testing for both passive and active response conditions.

Nasopharyngeal carcinoma in childhood and adolescence: concept and preliminary results of the cooperative GPOH study NPC-91. Gesellschaft für Pädiatrische Onkologie und Hämatologie.

BACKGROUND: The increasing use of chemotherapy has improved the prognosis of patients with nasopharyngeal carcinoma (NPC), and the authors demonstrated the beneficial effect of adjuvant interferon (IFN)-beta in a previous pilot study of children with advanced stage NPC. The current multi-institutional, cooperative GPOH (Gesellschaft für Pädiatrische Onkologie und Hämatologie) study NPC-91 was begun in 1992 to determine the efficacy of preradiation chemotherapy, radiotherapy, and adjuvant IFN-beta, in the treatment of advanced stage NPC. METHODS: Of a total of 22 patients, 21 had American Joint Committee on Cancer Stage III or IV disease, and 1 had Stage II disease. The median age was 12 years (range, 8-16 years). Twenty of 22 received 3 courses of preradiation chemotherapy consisting of methotrexate 120 mg/m2 on Day 1, cisplatin 100 mg/m2 on Day 1, and 5-fluorouracil 1000 mg/m2 for five days as well as 6 doses of leucovorin 25 mg/m2 every six hours beginning on Day 2. The Stage II patient received no chemotherapy, and chemotherapy was terminated for another during the first course. All patients had radiation therapy, stratified by stage. The cumulative dose to the primary sites was 59.4 gray (Gy), with single doses of 1.8 Gy. A total of 45 Gy was delivered to the neck area. Finally, all patients were treated with recombinant IFN-beta (10(5) U per kg of body weight) 3 times a week for 6 months. RESULTS: The response rate was 91%. These patients stayed in first remission during a median follow-up of 32 months. With the exception of one reversible cardiotoxicity, moderate chemotherapy-related toxicity was observed. CONCLUSIONS: In this study, patients with advanced stage NPC had a good prognosis with treatment consisting of neoadjuvant cisplatin and 5-fluorouracil, radiotherapy, and adjuvant IFN-beta. It is particularly noteworthy that distant metastases did not develop.

Severe cardiotoxicity of high-dose 5-fluorouracil in combination with folinic acid, cisplatin and methotrexate in a 14-year-old boy with nasopharyngeal carcinoma (Schmincke tumor).

Cardiotoxicity by 5-fluorouracil has been reported as a rare complication in treatment protocols for adult patients with different malignant diseases. The combination with folinic acid as a biomodulatory substance and other cytotoxic drugs has been introduced to render protocols more effective and less toxic. We report severe but completely reversible cardiotoxicity of a treatment protocol for nasopharyngeal tumor (Schmincke tumor) of pediatric patients consisting of 5-fluorouracil, methotrexate, cisplatin and folinic acid in a 14-year-old boy who had no preexisting cardiac disease. The pathomechanism is briefly discussed.

Effect of Viscum album L. on rapidly proliferating amniotic fluid cells. Sister chromatid exchange frequency and proliferation index.

Amniotic fluid cells (AFC) from 10 women undergoing amniocentesis were investigated. The 5-bromo-2'-deoxyuridine-induced sister chromatid exchange (SCE) frequency of AFC remained stable after the addition of a therapeutical concentration of Viscum album L. preparation Iscador P but decreased significantly after administration of high drug doses. As the proliferation index remained stable, even at extremely high drug concentrations, this effect could not be ascribed to a reduction of proliferation. No indications of cytogenetic damage or effects of mutagenicity were seen after the addition of Viscum album L. preparation P.

[Value of preoperative colonoscopy in colon-rectal neoplasms]. / Valor de la colonoscopia preoperatoria en el cancer colo-rectal.

The surgical approach to treat colo-rectal carcinoma is usually based on the findings of barium enema. In 102 patients we reviewed the yield of pre-operative colonoscopy. Barium enema revealed the cancer in 76 of 84 patients (91%), whereas colonoscopy did so in 96 of 102 subjects (94%). In addition, 5 associated cancerous lesions were demonstrated by colonoscopy and none by barium enema. Associated benign lesions were seen in 14 patients. In 5 patients the surgical plan based on the barium enema was modified by the findings at colonoscopy. Eight false negatives to barium enema were correctly diagnosed by colonoscopy. We conclude that colonoscopy yields valuable information, beyond that of barium enema, in patients with colo-rectal cancer.

Monoclonal antibodies to plant growth regulators. II. Indole-3-acetic acid.

The production and characterization of high-affinity monoclonal antibodies suitable for the radio- and enzymeimmunoassay of the endogenous plant growth regulator, indole-3-acetic acid (IAA), is reported. Hybridomas were produced by fusion of NS 1 myeloma cells with spleen cells from Balb/c mice immunized with IAA-bovine serum albumin conjugates. From an initial collection of 158 wells containing cells secreting monoclonal antibodies against IAA, seven were used to derive cell clones. Three of these are described here. They secrete immunoglobulin (IgG2a or IgG2b) of high affinity and specificity for IAA methyl ester and can be used to quantite picogram amounts of this compound in plant extracts by radio- and enzymeimmunoassay.