methylcellulose and Breast-Neoplasms

Gastrointestinal disturbances, such as nausea and vomiting, are considered amongst the main adverse effects associated with oral anticancer drugs due to their fast release in the gastrointestinal tract (GIT). Sustained release formulations with proper release profiles can overcome some side effects of conventional formulations. The current study was designed to prepare sustained release tablets of Capecitabine, which is approved by the Food and Drug Administration (FDA) for the treatment of advanced breast cancer, using hydroxypropyl methylcellulose (HPMC), carbomer934P, sodium alginate, and sodium bicarbonate. Tablets were prepared using the wet granulation method and characterized such that floating lag time, total floating time, hardness, friability, drug content, weight uniformity, and in vitro drug release were investigated. The sustained release tablets showed good hardness and passed the friability test. The tablets' floating lag time was determined to be 30-200 seconds, and it floated more than 24 hours and released the drug for 24 hours. Then, the stability test was done and compared with the initial samples. In conclusion, by adjusting the right ratios of the excipients including release-retarding gel-forming polymers like HPMC K4M, Na alginate, carbomer934P, and sodium bicarbonate, sustained release Capecitabine floating tablet was formulated.

Topics: Acrylic Resins; Alginates; Breast Neoplasms; Capecitabine; Chemistry, Pharmaceutical; Deoxycytidine; Drug Dosage Calculations; Female; Fluorouracil; Gastrointestinal Diseases; Glucuronic Acid; Hexuronic Acids; Humans; Hypromellose Derivatives; Methylcellulose; Sodium Bicarbonate; United States; United States Food and Drug Administration

A major goal of experimental and clinical hematology is the identification of mechanisms and conditions supporting the expansion of transplantable hematopoietic stem cells. We assessed the expansion potential of CD34+CD71-CD45- cells derived from granulocyte colony-stimulating factor (G-CSF)-mobilized peripheral blood under recently defined serum-free culture conditions. The CD34+CD71-CD45- cells in mobilized peripheral blood were found to contain the majority (92%+/-5.6) of primitive long-term culture initiating cells (LTCIC) and 53.5%+/-16.7 of the more committed colony-forming cells (CFC). Furthermore, this population represents 23.3%+/-4.1 of the total CD34+ cells and allows reduction of the cell density important for maintenance/expansion of primitive progenitor cells. CD34+ CD71- CD45- cells were cultured in defined serum-free media supplemented with 300 ng each of Flt-3 ligand and stem cell factor (SCF), 60 ng of interleukin (IL)-3, and 20 ng each of IL-6 and G-CSF. Mononuclear cells (MNC) and CFC were expanded 50-fold and 200-fold, respectively; primitive progenitor cells (LTC-IC) were maintained at input values after a total of 10 days of expansion. The addition of IL-15 to our cytokine cocktail expanded LTC-IC 2- to 3-fold and CFC to >500-fold. The data presented should allow clinical manipulation (purging) and expansion procedures with mobilized PBPC harvests without the loss of primitive progenitor cells and could be made applicable for large-scale clinical expansion.

Topics: ADP-ribosyl Cyclase; ADP-ribosyl Cyclase 1; Antigens, CD; Antigens, CD34; Antigens, Differentiation, B-Lymphocyte; Breast Neoplasms; Cells, Cultured; Culture Media, Serum-Free; Erythropoietin; Granulocyte Colony-Stimulating Factor; Granulocyte-Macrophage Colony-Stimulating Factor; Hematopoietic Stem Cells; Humans; Interleukin-15; Interleukin-3; Interleukin-6; Leukocyte Common Antigens; Lymphoma, Non-Hodgkin; Membrane Glycoproteins; Membrane Proteins; Methylcellulose; Receptors, Transferrin; Stem Cells

Topics: Antigens, CD; Antigens, CD34; Blood Cells; Bone Marrow Transplantation; Breast Neoplasms; Cells, Cultured; Colony-Forming Units Assay; Female; Fibrin; Hematopoietic Stem Cell Transplantation; Hematopoietic Stem Cells; Humans; In Vitro Techniques; Leukapheresis; Megakaryocytes; Methylcellulose; Thrombocytopenia; Transplantation, Autologous

Topics: Adult; Aged; Breast Neoplasms; Carboxymethylcellulose Sodium; Drug Evaluation; Female; Humans; Interferon Inducers; Methylcellulose; Middle Aged; Neoplasm Metastasis; Poly I-C; Polylysine

Thirty-seven samples of human primary breast cancer were processed for direct cloning in methylcellulose (MC) cultures. Of the 37 specimens plated, 19 tumors (51%) grew with a plating efficiency (PE) of 0.012%. Both growing and nongrowing tumors belonged mostly to the ductal histologic type. The use of autologous serum v fetal calf serum did not affect the PE. Moreover, a negative correlation was found between the level of estrogen receptors and especially of progesterone receptors (PRs) and the ability of tumors to grow in MC culture. These findings underline the difficulty of cloning fresh specimens of human solid tumors and indicate that malignant cells with a high concentration of PRs may also have a degree of differentiation that leads to a reduced clonogenic ability.

Topics: Breast Neoplasms; Carcinoma, Intraductal, Noninfiltrating; Clone Cells; Culture Media; Culture Techniques; Female; Humans; Methylcellulose; Receptors, Progesterone

Possible mechanisms responsible for expression of anchorage independence were investigated with the use of the human breast carcinoma cell line Hs578T. This phenotype was not stable and most likely occurred via alterations in gene expression, causing secretion of growth factor (s). Colony-forming efficiency in methylcellulose was proportional to initial plating density at low passage number and increased with passage in culture. At high passages, there was less sensitivity to initial plating density, suggesting less dependence on surrounding cells for feeding effects. Clonal variants isolated in methylcellulose maintained a higher plating efficiency when kept in suspension, and removal of selective pressure resulted in the loss of the high level of expression upon subsequent challenge in suspension. In contrast to other systems, anchorage-dependent clones acquired the ability to grow in methylcellulose after only one passage in culture. This suggests that rapid variation at rates not typical of classical somatic mutation plays a role in expression of anchorage independence. Exposure to 5-azacytidine, which decreases methylation of DNA and may thereby activate gene transcription, increased the incidence of anchorage-independent growth 20 times; whereas treatment with 6-azacytidine had no effect. Unconcentrated medium conditioned by cells previously exposed to 5-azacytidine or by cells at high passage stimulated growth in suspension by as much as 10.9 times. The factor(s) present in this conditioned medium was stable to heat up to 63 degrees C for 30 minutes and was larger than 12,000-14,000 mol wt as determined by dialysis.

Topics: Azacitidine; Breast Neoplasms; Carcinosarcoma; Cell Adhesion; Cell Division; Cell Line; Culture Media; Female; Gene Expression Regulation; Hot Temperature; Humans; Isomerism; Methylcellulose; Phenotype

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