methylcellulose and Melanoma

Dabrafenib is a small-molecule inhibitor of BRAF kinase activity that is currently being developed for the treatment of BRAF V600 mutation-positive melanoma. This clinical, open-label, two-cohort (n = 14 per cohort), randomized study was designed to evaluate the effect of drug substance particle size, and food on the plasma pharmacokinetics of a single oral dose of dabrafenib in patients with BRAF V600 mutation-positive solid tumors. In addition, an exploratory cross-cohort comparison of the relative bioavailability of single-dose dabrafenib administered in gelatin and hydroxypropyl methylcellulose (HPMC) capsules was performed. Higher bioavailability was noted with nonmicronized drug substance (larger particle size), under fasting conditions, and with HPMC capsules. Initial dissolution results at pH 1.2 showed higher dissolution of gelatin relative to HPMC capsules inconsistent with clinical data. Subsequent in vitro dissolution studies were conducted in fasted-state simulated gastric fluid over a 24-h period and showed that HPMC capsules reached a higher percentage of dabrafenib dissolved than gelatin capsules. The presence of HPMC is believed to inhibit precipitation of dabrafenib as the freebase, thereby maintaining a supersaturated solution over an extended period of time. Dabrafenib has been administered in pivotal clinical studies on an empty stomach using micronized drug substance in HPMC capsules.

Topics: Administration, Oral; Adult; Aged; Antineoplastic Agents; Biological Availability; Capsules; Cohort Studies; Fasting; Female; Humans; Hypromellose Derivatives; Imidazoles; Male; Melanoma; Methylcellulose; Middle Aged; Oximes; Particle Size; Point Mutation; Proto-Oncogene Proteins B-raf

Topics: Apoptosis; Cell Line, Tumor; Humans; Melanoma; Methylcellulose; Myeloid Cell Leukemia Sequence 1 Protein; Proto-Oncogene Proteins c-bcl-2

Cells aggregate on an original cellulose substratum (CEL). This influences the signaling programs of adhering cells. CEL thus appears to be a suitable tool for studying the regulation of cell-substratum and cell-cell interactions.

Topics: Animals; Carboxymethylcellulose Sodium; Cell Adhesion; Cell Aggregation; Cell Culture Techniques; Cell Line, Tumor; Humans; Hypromellose Derivatives; Melanoma; Methylcellulose

Preparation of suspension of anchorage-dependent cells growing in tissue cultures requires removal of the cells from their substrata by means of trypsin and/or EDTA. The purpose of the experiments was to investigate the effect of methylcellulose on the adhesive ability of cells removed from substrata by EDTA and trypsin. Human umbilical cord vein endothelial cells (HUVEC), after detachment from substrata, adhere well to fibronectin at 37 degrees C but not at 0 degrees C. During a 60-min incubation at 37 degrees C, these cells lose about 70% of their ability to adhere to fibronectin. The ability of cells to adhere was restored in the presence of 0.2% methylcellulose. Methylcellulose also prevented human skin fibroblasts, human melanoma cells and mouse lung fibroblasts from losing adhesive properties. By contrast, it did not affect the adhesive ability of B16F10 melanoma cells incubated at 37 degrees C. In conclusion, our study suggests that methylcellulose can be a useful reagent for preservation of cell function in suspension; it may also simplify some experimental procedures including radioiodination of cell surface components and cross-linking of radiolabeled ligands to the cell surface.

Topics: Animals; Cell Adhesion; Cell Separation; Cells, Cultured; Edetic Acid; Endothelium, Vascular; Fibroblasts; Humans; Lung; Melanoma; Methylcellulose; Mice; Skin; Tissue Preservation; Trypsin; Tumor Cells, Cultured; Umbilical Veins

Sixteen patients with metastatic malignant melanoma were treated with poly(I,C)-LC 5 mg/m2 twice weekly by intravenous injection. No antitumor responses occurred. Fever (frequently greater than 40 degrees C) and fatigue were dose limiting toxicities. One patient developed a fever of 42.2 degrees C when poly(I,C)-LC was given on 2 consecutive days. Interferon was consistently detected in the serum 8 h after a single injection of poly(I,C)-LC (median titer 199 U/ml). No enhancement of interferon induction was detected on the second day when poly(I,C)-LC was given on 2 consecutive days.

Topics: Adult; Aged; Antineoplastic Agents; Carboxymethylcellulose Sodium; Drug Evaluation; Fatigue; Female; Fever; Humans; Interferons; Male; Melanoma; Methylcellulose; Middle Aged; Poly I-C; Polylysine

Topics: Adjuvants, Immunologic; Animals; Carboxymethylcellulose Sodium; Hypersensitivity, Delayed; Leukemia L1210; Male; Melanoma; Methylcellulose; Mice; Mice, Inbred Strains; Peptides; Poly I-C; Polylysine; Polymers; Pyran Copolymer; Vaccines

A serum-free medium has been developed which supports colony formation by cells from several human tumor cell lines, one colon adenocarcinoma (WiDr) and four melanoma (Me43, Me85, MP6, MeIuso). This medium consists of a 1:1 mixture of an enriched Dulbecco's modified Eagle's medium (EMED) and a modified Ham's F-12 nutrient mixture (FMED) supplemented with 0.9% methylcellulose, 1% bovine serum albumin, 80 micrograms/ml human transferrin, 3 micrograms/ml insulin, 2.8 micrograms/ml linoleic acid, 2.6 micrograms/ml cholesterol, 20 microM ethanolamine, and trace elements. Colony formation by WiDr cells is linear with the numbers of cells plated, having a plating efficiency (PE) of 34%, as compared to 26% in serum-containing medium. Two of the melanoma cell lines. MP6 and MeIuso, exhibit linear relationships between colony numbers and cell concentration with PEs of 21% and 70% respectively. Colony formation by the other two melanoma cell lines appears to be nonlinear. This work represents a step toward standardizing culture conditions for human tumor clonogenic cell assays.

Topics: Adenocarcinoma; Cell Aggregation; Cell Division; Cell Line; Colonic Neoplasms; Colony-Forming Units Assay; Culture Media; Humans; Melanoma; Methylcellulose; Serum Albumin, Bovine; Tumor Stem Cell Assay

Topics: Agar; Biopsy; Breast Neoplasms; Cell Survival; Clone Cells; Culture Techniques; Female; Humans; Lung Neoplasms; Male; Melanoma; Methylcellulose; Microscopy, Electron; Neoplasms; Pleural Effusion

The correlation of the colony growth of cells disaggregated from human melanoma, sarcoma, lung, and ovarian carcinomas were studied in four different semisolid tissue culture assays: (a) the soft agar assay of Pluznik and Sachs; (b) the soft agar assay of Hamburger and Salmon; (c) the soft agar-methyl cellulose assay of Buick et al.; and (d) the methyl cellulose assay of Ogawa et al. There was no colony growth of tumor cells achieved in 15 of 15 cases assayed in Ogawa's methyl cellulose assay. The plating efficiency of the above mentioned tumors was similar in the assays of Pluznik and Sachs, Hamburger and Salmon, and Buick et al. However, the tumor take rate differed among these three systems. The assay of Buick et al. appears potentially useful for analysis of the biology of human tumors.

Topics: Adenocarcinoma; Agar; Cell Division; Cells, Cultured; Cytological Techniques; Female; Humans; Lung Neoplasms; Melanoma; Methylcellulose; Ovarian Neoplasms; Sarcoma

Topics: Acrylic Resins; Adolescent; Adult; Aged; Child; Child, Preschool; Eye Diseases; Eye Injuries; Eye Neoplasms; Eye, Artificial; Female; Follow-Up Studies; Glaucoma; Humans; Male; Melanoma; Methods; Methylcellulose; Middle Aged; Nystagmus, Pathologic; Ophthalmic Solutions; Ophthalmologic Surgical Procedures; Pemphigus; Postoperative Complications; Silicones; Suture Techniques; Trachoma