minocycline and Adenocarcinoma

We investigated the effectiveness and complications of intrathoracic infusion with a combination of cisplatin, OK-432, and minocycline for malignant pleural effusion. All patients were hospitalized with chest tube drainage of pleural effusion until the daily drainage volume was less than 100 ml. Twenty-five mg of minocycline, 1 to 3 KE of OK-432, and 5 to 10 mg of cisplatin were instilled into the pleural space. The administration was repeated until drainage effusion disappeared. Therapeutic effect was evaluated according to the following criteria: (1) excellent, no fluid reaccumulation for at least 4 weeks as determined by chest radiogram and clinical evaluation; (2) effective, fluid reaccumulation less than 50% of original effusion with no need of thoracentesis for symptomatic relief within 4 weeks after treatment; and (3) failure, reaccumulation of more than 50% of the original effusion requiring thoracentesis to relieve symptoms within 4 weeks of treatment. Twelve patients with malignant effusion received the combination treatment; 11 patients had primary lung cancer and one had metastatic lung tumor from cancer of the rectum. In all cases, the histology or cytology revealed adenocarcinoma. Eleven of the 12 patients had an excellent response with relief of clinical symptoms. The remaining case failed to show any improvement. Complications such as local pain, fever, nausea, and vomiting were mild and transient. We conclude that combination administration of low-dose minocycline, OK-432, and cisplatin into the thoracic cavity for malignant effusion is an effective alternative treatment with the potential for improvement of the general condition and reduced morbidity.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Dose-Response Relationship, Drug; Drainage; Drug Administration Schedule; Female; Humans; Infusions, Intralesional; Lung Neoplasms; Male; Middle Aged; Minocycline; Picibanil; Pleural Effusion, Malignant; Thoracic Cavity

It has been known that treatments of post-pneumonectomy empyema are difficult. We report a successful case of irrigation for the post-pneumonectomy. The patient was 68-year-old man with advanced lung cancer. He underwent induction chemoradiotherapy following by pneumonectomy of the right side. A few days later after the chest drain was withdrawn, spike fever appeared. Empyema was suspected, so a 28 Fr diameter double lumen chest drain was intubated again. Turbid effusion was discharged through the drain, in which methicillin-resistant staphylococcus aureus (MRSA) was cultured. Irrigation using a lot of saline and acid electrolyzed water started. A month later, irrigator through the drain was looking clear, however, MRSA was cultured so far. After putting minomycine into the irrigator, MRSA died away. This physical and chemical irrigations were effective.

Topics: Adenocarcinoma; Aged; Empyema, Pleural; Humans; Lung Neoplasms; Male; Methicillin Resistance; Minocycline; Pneumonectomy; Postoperative Complications; Staphylococcal Infections; Therapeutic Irrigation

Bone metastases are a common complication in prostate and breast cancer patients. It leads to extensive morbidity and eventually mortality. Matrix metalloproteinases are implicated in various steps of development of metastasis, through their ability to degrade the extracellular matrix. Increased matrix metalloproteinase activity of tumor cells has been associated with a higher metastatic potential. Inhibitors of metalloproteinases have been shown to effectively reduce or prevent the formation of metastases. The family of tetracyclines is able to inhibit matrix metalloproteinase activity through chelation of the zinc ion at the active site of the enzyme. Using tumor cell lines relevant to bone metastases, i.e. PC-3, MDA-MB-231, Hs696, B16/F1, we showed that tetracycline and derivatives of tetracycline, namely doxycycline and minocycline, also induced cytotoxicity. The effective concentrations are relatively high for plasma, but are clinically achievable in the bone, since tetracyclines are osteotropic. All four bone-metastasizing tumor cells produced and secreted various matrix metalloproteinases. Doxycycline was able to inhibit the activity of 72- and 92-kDa type IV collagenase secreted by bone-metastasizing cells by 79-87%. These characteristics could make tetracycline a unique candidate as a therapeutic agent to prevent bone metastases in cancer patients with a high likelihood for development of bone metastasis. Studies using animal models of experimental bone metastasis will be necessary to confirm this.

Topics: Adenocarcinoma; Animals; Anti-Bacterial Agents; Blotting, Western; Bone Neoplasms; Breast Neoplasms; Cell Survival; Collagenases; Culture Media, Conditioned; Doxycycline; Extracellular Matrix; Gelatinases; Humans; Male; Matrix Metalloproteinase 1; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Matrix Metalloproteinase Inhibitors; Melanoma; Metalloendopeptidases; Mice; Minocycline; Prostatic Neoplasms; Protease Inhibitors; Tetracycline; Tetracyclines; Tumor Cells, Cultured

Degradation of the extracellular matrix by metalloproteinases is a critical phenomenon in cancer invasion and metastasis. Recent studies have revealed that minocycline (minocycline hydrochloride, a tetracycline) suppresses in vivo and in vitro mammalian collagenolytic activity. We investigated whether minocycline inhibited in vitro invasion and experimental pulmonary metastasis in subline-2 of streptozotocin-induced mouse renal adenocarcinoma (MRAC-PM2) cells. In vitro invasion assay demonstrated that treatment with 0.5 microgram/ml or 5.0 micrograms/ml minocycline significantly inhibited the invasion of MRAC-PM2 cells. In addition, intraperitoneal administration of 0.5 mg per mouse minocycline reduced the number of metastatic nodules in the lung when MRAC-PM2 cells were injected intravenously. Minocycline also suppressed type IV collagenolytic activity of the cells. However, the drug did not affect [3H]-thymidine uptake, growth of subcutaneously inoculated cells, attachment to the extracellular matrices, or haptotactic migration of the cells. These results indicated that the inhibitory action of type IV collagen degradation by minocycline can contribute, in part, to suppression of the in vitro invasion and metastatic potential of MRAC-PM2 cells.

Topics: Adenocarcinoma; Animals; Cell Adhesion; Collagen; DNA, Neoplasm; In Vitro Techniques; Kidney Neoplasms; Lung Neoplasms; Mice; Mice, Inbred Strains; Minocycline; Neoplasm Invasiveness; Neoplasm Transplantation; Streptozocin; Tumor Cells, Cultured