minocycline and Breast-Neoplasms

The patient was a 56-year-old woman who had undergone the Patey operation for left breast cancer when she was 45 years old. She had complained of dyspnea and shortness of breath at the time of exercise. Bilateral accumulation of pleural effusion and pericardial fluid was observed on chest radiographs and computed tomography(CT)scans. Under the diagnosis of cardiac tamponade, the patient was treated with pericardial drainage and local chemotherapy(intra-pericardial dosage of paclitaxel 45 mg and minocycline 100 mg)with the aim of preventing the accumulation of pericardial effusion. Subsequently, the pericardial effusion continued to disappear. The patient was treated with systemic chemotherapy. At the age of 58 years, she died of breast cancer. After treatment with pericardial drainage and local chemotherapy, she did not experience pericardial reaccumulation or cardiac tamponade. Thus, the method of local chemotherapy(intra-pericardial dosage of paclitaxel 45 mg and minocycline 100 mg)was considered effective.

Topics: Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Cardiac Tamponade; Combined Modality Therapy; Female; Humans; Middle Aged; Minocycline; Paclitaxel; Pericardial Effusion

Chryseobacterium meningosepticum is a ubiquitous Gram-negative bacillus historically associated with meningitis in premature neonates. We report 15 positive cultures and 6 cases of infection among immunocompromised adults at our institution over a 10-year period and review the English-language literature on C. meningosepticum. Excluding the present series, there are 308 reports of positive cultures in the literature, of which 59% were determined to represent true infections. Sixty-five percent of those infected were younger than 3 months of age. Meningitis was the most common infectious syndrome among neonates, seen in 84% of cases and associated with a 57% mortality rate. Less commonly reported infections among infants included sepsis (13%) and pneumonia (3%). Pneumonia was the most frequent infection among the postneonatal group, accounting for 40% of cases, followed by sepsis (24%), meningitis (18%), endocarditis (3%), cellulitis (3%), abdominal infections (3%), eye infections (3%), and single case reports of sinusitis, bronchitis, and epididymitis. The 6 cases in our series were all adults, with a mean age of 58.7 years. Sites of C. meningosepticum infection were limited to the lungs, bloodstream, and biliary tree. Infection in our series was associated with prolonged hospitalization, prior exposure to multiple antibiotics, and host immunocompromise, particularly neutropenia. C. meningosepticum is resistant to multiple antibiotics, and disk dilution is notoriously unreliable for antibiotic sensitivity testing. Sensitivity testing on the 15 isolates from our institution revealed the most efficacious antibiotics to be minocycline (100% sensitive), rifampin (93%), trimethoprim-sulfamethoxazole (67%), and ciprofloxacin (53%). In contrast to reports in the literature, the isolates in our series displayed widespread resistance to vancomycin (100% resistant or intermediately sensitive), erythromycin (100%), and clindamycin (86%). These findings have important implications for the clinician when choosing empiric antibiotic regimens for patients with risk factors for C. meningosepticum infection.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotics, Antitubercular; Breast Neoplasms; Ciprofloxacin; Drug Resistance, Microbial; Female; Flavobacterium; Gram-Negative Bacterial Infections; Humans; Immunocompromised Host; Infant; Infant, Newborn; Leukemia, Myeloid, Acute; Liver Transplantation; Male; Meningitis, Bacterial; Middle Aged; Minocycline; Pneumonia, Bacterial; Rifampin; Sepsis; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Acneiform Eruptions; Administration, Topical; Adult; Antibodies, Monoclonal, Humanized; Benzoyl Peroxide; Breast Neoplasms; Carcinoma, Ductal, Breast; Clindamycin; Drug Eruptions; Female; Humans; Middle Aged; Minocycline; Receptor, ErbB-2; Trastuzumab

Development of peripheral neuropathy, which can present as painful neuropathy or loss of sensation, sometimes limit the use of paclitaxel in the treatment of solid tumors such as breast cancer. Previous studies reported development of thermal hyperalgesia in mice treated with paclitaxel. In this study an automated flinch detection system for the formalin test (20 μl of 5% formalin injected subcutaneously into the paw dorsum) was used to evaluate chemical nociception in BALB/c mice treated with paclitaxel 2 mg/kg alone or coadministered with minocycline 50 mg/kg, intraperitoneally for 5 consecutive days. Reaction latency to thermal stimuli (hot-plate) was also measured. Injection of formalin resulted in biphasic paw flinches; phase 1 (1-9 minutes) and phase 2 (10-40 minutes). Treatment with paclitaxel reduced cumulative flinches in both phases 1 and 2 by 28% and 43%, respectively at day 7. However, treatment with paclitaxel also induced thermal hyperalgesia. Co-administration of paclitaxel with minocycline prevented development of both paclitaxel-induced hyposensitivity to chemical nociception and thermal hyperalgesia. In conclusion, the results indicate paclitaxel induces chemical hyposensitivity and thermal hyperalgesia in mice. Minocycline protected against paclitaxel-induced chemical hyposensitivity and thermal hyperalgesia, thus, providing further support of the usefulness of the drug in prevention of chemotherapy-induced neuropathy.

Topics: Animals; Breast Neoplasms; Female; Formaldehyde; Humans; Hyperalgesia; Mice; Minocycline; Nociception; Paclitaxel; Peripheral Nervous System Diseases

For breast reconstruction, the deep inferior epigastric perforator (DIEP) flap has become standard therapy. A feared complication is partial or even total flap loss. In a novel murine model of partial DIEP flap loss, the contribution of apoptotis to flap loss was investigated. The clinically available apoptosis-inhibiting compound minocycline was tested for its ability to reduce cell death. The effect of minocycline on cell proliferation was studied in cell cultures of breast carcinoma. In 12 mice, pedicled DIEP flaps were raised, which were subjected to 15 minutes of ischemia and 4 days of reperfusion. Six mice were treated with minocycline 2 hours before surgery and every 24 hours for 4 days. Apoptosis was revealed by injecting annexin A5 30 minutes before sacrifice. Annexin A5 binds to phosphatidylserines, which are expressed on the cell membrane during apoptotis. Prior to sacrifice, necrosis was measured using planimetry. Minocycline reduced cell death after 4 days from 35.9% (standard deviation = 10.6) to 13.9% (standard deviation = 8.0; P < 0.05). Apoptosis, as shown by annexin A5 binding in nontreated animals, was abundant. Minocycline did not influence tumor growth in cell cultures of human breast cancer. Minocycline treatment leads to increased DIEP flap viability in mice. This study widens the perspective in the improvement of free flap survival in patients.

Topics: Animals; Apoptosis; Biopsy, Needle; Breast Neoplasms; Cell Death; Cell Line, Tumor; Disease Models, Animal; Epigastric Arteries; Female; Graft Rejection; Immunohistochemistry; Injections, Subcutaneous; Mammaplasty; Mice; Minocycline; Random Allocation; Rectus Abdominis; Reference Values; Regional Blood Flow; Surgical Flaps

Breast carcinomas show a trend toward bone metastasis that is prevalent worldwide. Celecoxib (CX) and minocycline hydrochloride (MH) have both been widely used in treating breast cancer; however, their combined effects on the osseous metastasis of breast cancer have not yet been studied. In the present study, breast cancer cells were injected into the back of the femoral bone of nude mice, and CX and MH were intraperitoneally administered every other day at doses of 30 and 40 mg/kg/day, respectively, for 30 days. Tumor weights and volumes were significantly lower and the tumor inhibition rate was significantly higher in the CX + MH group than those of the control and CX or MH alone groups (p < 0.05). The cell density in the tumor tissue was significantly decreased and apoptotic and necrotic cell death was significantly increased in the CX + MH group, as compared with those of the control and CX or MH alone groups. Microvessel density and expression of vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 in the tumor tissues of the CX + MH group were significantly lower than those of the CX, MH, and control groups. The serum alkaline phosphatase level of the CX + MH group was significantly lower than those of the other groups (p < 0.01). These results suggest that a combined use of CX and MH has better inhibitory effects on the osseous metastasis of breast cancer, as compared to CX or MH alone. They exerted their combined effects by increasing tumor-cell death and decreasing the tumor expression of MMP-9 and VEGF systems.

Topics: Alkaline Phosphatase; Animals; Apoptosis; Body Weight; Bone Neoplasms; Breast Neoplasms; Celecoxib; Cell Line, Tumor; Cyclooxygenase Inhibitors; Drug Therapy, Combination; Female; Humans; Matrix Metalloproteinase 9; Mice; Mice, Inbred Strains; Mice, Nude; Minocycline; Pyrazoles; Sulfonamides; Tumor Burden; Vascular Endothelial Growth Factor A; Xenograft Model Antitumor Assays

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

Minocycline pleurodesis with intrapleural pretreatment of lidocaine (150 mg) was performed on 19 patients. Minocycline was instilled into the pleural space for postoperative air leakage in 12 patients and control of malignant pleural effusion in 7 patients. Postoperative air leakage persisted longer than seven days was indicated instillation of minocycline (300 mg) with thoracostomy drainage. Satisfactory results were obtained in 11 of the 12 patients (92%) treated with this method. In 7 patients to control malignant pleural effusion, only one of these patients had recurrence of pleural effusion. Seventeen patients of all 19 subjects were free of pain following pleurodesis. None of these patients had a side effect of lidocaine. In conclusion of instillation, minocycline with thoracostomy drainage is a safe and an effective technique.

Topics: Adult; Aged; Aged, 80 and over; Breast Neoplasms; Drug Evaluation; Female; Humans; Instillation, Drug; Lung Neoplasms; Male; Middle Aged; Minocycline; Pleural Effusion; Pneumonectomy; Pneumothorax; Postoperative Complications; Tetracyclines; Thorax