minocycline and Stomach-Neoplasms

Tigecycline acts as a glycylcycline class bacteriostatic agent, and actively resists a series of bacteria, specifically drug fast bacteria. However, accumulating evidence showed that tetracycline and their derivatives such as doxycycline and minocycline have anti-cancer properties, which are out of their broader antimicrobial activity. We found that tigecycline dramatically inhibited gastric cancer cell proliferation and provided an evidence that tigecycline induced autophagy but not apoptosis in human gastric cancer cells. Further experiments demonstrated that AMPK pathway was activated accompanied with the suppression of its downstream targets including mTOR and p70S6K, and ultimately induced cell autophagy and inhibited cell growth. So our data suggested that tigecycline might act as a candidate agent for pre-clinical evaluation in treatment of patients suffering from gastric cancer.

Topics: AMP-Activated Protein Kinases; Animals; Anti-Bacterial Agents; Antineoplastic Agents; Autophagy; Cell Line, Tumor; Cell Proliferation; Humans; Mice; Mice, SCID; Minocycline; Ribosomal Protein S6 Kinases, 70-kDa; Signal Transduction; Stomach Neoplasms; Tigecycline; TOR Serine-Threonine Kinases; Tumor Cells, Cultured; Xenograft Model Antitumor Assays

Assessment has been made, using MIC values and coagulase types, of 214 strains of Staphylococcus aureus isolated from the lesions of inpatients at the First Surgical Department, Hiroshima University, from 1983 to 1988. The obtained results are summarized below: 1. Frequency of MRSA among all the strains of S. aureus during a period from 1983 to 1987 was higher than 50%. 2. Highly methicillin-resistant strains (MIC of methicillin greater than 100 micrograms/ml) emerged in 1984 and thereafter, showed a trend of increase through 1987. 3. The highly methicillin-resistant strains are of coagulase II type strain and they are considered to be inhospital epidemic strains. 4. Both ofloxacin and minocycline (MINO) showed good activities against highly methicillin-resistant strains, but many resistant strains were resistant to beta-lactam and aminoglycoside agents. Based on the above basic assessment, chemotherapies mainly using MINO were performed on cases of MRSA infections experienced at the First Surgical Department, Hiroshima University in a period from July, 1987, to November, 1988, and the following results were obtained. 1. Drugs used were: single MINO in 2 cases; MINO+imipenem/cilastatin (IPM/CS) in 4 cases; MINO+IPM/CS+tobramycin in 1 case; MINO+cefmetazole (CMZ) in 1 cases; and MINO+fosfomycin+CMZ (changed to MINO+Amikacin) in 1 case, a total of 9 cases. Clinical result showed remarkable effectiveness of these therapies in 3 cases with some degrees of effectiveness in 6 cases, thus the therapies were all effective or better. 2. No particular abnormality was observed in subjective or objective symptoms or clinical laboratory tests, judged from values obtained before and after administration of MINO. The above results agreed with well those of the basic assessment, suggesting the possibility that the chemotherapies mainly using MINO would exhibit effectiveness on MRSA infections.

Topics: Adult; Aged; Cefmetazole; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Humans; Imipenem; Male; Methicillin; Middle Aged; Minocycline; Penicillin Resistance; Postoperative Complications; Staphylococcal Infections; Staphylococcus aureus; Stomach Neoplasms; Tetracyclines