minocycline and Prostatic-Neoplasms

Metastatic prostate cancer is one of the leading causes of cancer death in men. Although initially responsive to hormone therapy, it eventually progresses in almost all patients. For this reason, there has been a search for novel agents to use in the fight against androgen-independent prostate cancer. Antiangiogenesis is a relatively new antitumor strategy that has been employed in the treatments of many malignancies. As prostate cancer is likely dependent on angiogenesis for its growth and progression, it would logically serve as a good target for this modality. Initially met with great enthusiasm, antiangiogenic drugs have seen only limited success when used as single agents. This has been attributed to many possible etiologies including lack of cytotoxicity and use in situations of large tumor burden. In order to overcome these problems, many investigators are combining antiangiogenic agents with more traditional cytotoxic chemotherapy regimens in hope of augmenting the effects of either drug alone. This article will review the background of angiogenesis inhibition and the use of such combinations in metastatic prostate cancer.

Topics: Angiogenesis Inhibitors; Anti-Bacterial Agents; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Clinical Trials as Topic; Cyclohexanes; Humans; Male; Minocycline; Neovascularization, Pathologic; O-(Chloroacetylcarbamoyl)fumagillol; Paclitaxel; Prostatic Neoplasms; Sesquiterpenes

A 60-year-old man visited our hospital to treat a large cystic mass in the pelvis which had been found by abdominal ultrasonography in December 201X. Computed tomography (CT) and magnetic resonance imaging (MRI) showed a multilocular cyst with a maximum diameter of about 10 cm. CT-guided drainage and sclerotherapy with minocycline reduced the size of tumor by 40%, but symptoms such as difficulty of defecation and urinary frequency appeared a year and a half later due to re-enlargement of the cysts. Laparoscopic resection of the multilocular cysts was performed, and all cysts were removed almost completely using transrectal ultrasonography. The multilocular cyst was positive for NKX3.1 by immunohistochemical staining, and was diagnosed as a giant multilocular prostatic cystadenoma. After surgery, the symptoms such as difficulty of defecation and urinary frequency were relieved promptly. One year after the surgery, the patient was free from recurrence of the disease.

Topics: Cystadenoma; Cystectomy; Cysts; Humans; Laparoscopy; Male; Middle Aged; Minocycline; Pelvis; Prostatic Neoplasms

To elucidate a hypothetical link between retinoic acid (RA) signaling and minocycline for targeting prostate carcinoma (PCA). RA signaling has been implicated in growth-inhibition of malignant PCA, and intracellular RA homeostasis has been investigated as a potential therapeutic target. Minocycline is a tetracycline antibiotic with pleiotropic actions in many tissues and reaches comparably high levels in human prostate tissue. Interestingly, minocycline exhibits the rare side effect of a pseudotumor cerebri, which is otherwise known to occur from vitamin A intoxication or in retinoid therapy. Therefore, we hypothesized minocycline to putatively interact with intracellular RA homeostasis in PCA.. Using LN-CAP, DU-145, and PC-3 cell lines, effects of minocycline on microsomal RA metabolism and on cell growth were assessed in vitro.. Minocycline was identified to potently inhibit cell growth, at concentrations within the range of tissue levels readily reached under standard therapeutic conditions. In vitro inhibition experiments revealed inhibition of RA breakdown, yet only at comparably high concentrations of minocycline. Using all trans-RA, RA metabolism inhibitor liarozole, and different retinoid receptor antagonists, the putative RA-dependent effects of minocycline were further evaluated and confirmed to be independent of RA signaling.. Our findings add to the growing body of evidence for the many pleiotropic actions of minocycline. In view of the striking effects of minocycline on cell growth in PCA cell lines in vitro and its relatively safe side effect profile, the use of minocycline for targeting PCA should be timely clinically evaluated.

Topics: Cell Line, Tumor; Cell Proliferation; Humans; Male; Minocycline; Prostatic Neoplasms; Tretinoin

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

Eighty male patients, most of whom had suspicious prostatic nodules on digital examination, were subjected to transrectal needle biopsy of the prostate. The biopsy needle was held between the gloved hand and an overlying sterile finger cot on the index finger. When the lesion was palpated, the needle was pushed through the finger cot and a tissue specimen obtained. All patients were treated orally with minocycline hydrochloride 100 mg. twice a day starting eight to twelve hours before biopsy and continuing at this dosage for five days after biopsy. Except for one episode of transitory hematuria, there were no reports of infection or complication, as manifested by fever, chills, or transrectal or transurethral bleeding.

Topics: Administration, Oral; Biopsy, Needle; Female; Humans; Male; Minocycline; Prostatic Neoplasms; Time Factors

Topics: Adult; Aged; Cystitis; Drug Resistance, Microbial; Escherichia coli; Female; Humans; Infusions, Parenteral; Klebsiella; Male; Middle Aged; Minocycline; Postoperative Complications; Prostatic Hyperplasia; Prostatic Neoplasms; Proteus; Pseudomonas; Pyelonephritis; Staphylococcus; Tetracycline; Urologic Diseases