Doxycycline/Cancer Studies

Cancer/Doxycycline Studies 

Multiple studies found doxycycline has the ability to reduce or eliminate various forms of cancer and cancerous tumors. There is a higher than normal rate of people with Lyme disease developing cancer. Below is a news article in easy-to-read language. Following it are the actual studies mentioned in the article, and a list of more recent scientific studies linking doxycycline to cancer improvement.

Update- October 2018-  Existing Drug (Doxycycline) Can Reduce Breast Cancer Recurrence Risk-  "For the study, the researchers included just 15 participants. Of these, nine received doxycycline each day for 14 days, while remaining six participants were involved as a control and took no drugs. As a result, the researchers found a drop in CSCs [Cancer Stem Cells] in nearly all participants who took doxycycline."  

Update- December 2017-  Vitamin C and Antibiotic [Doxy] Can Kill Cancer Cells

Scientists find way to 'turn off' cancer 

Antibiotic halts aggressive tumours in mice

Tim Radford, Science Editor,

Monday October 11, 2004, The Guardian

Scientists in California have found a way to "turn off" a gene that makes cancerous cells lethal.

They eliminated aggressive, incurable liver tumours in laboratory mice in four weeks, they report in an advance paper in Nature today. The study, based on a gene called Myc, could lead to new ways of treating cancer.

Cancer Research UK scientists in Glasgow, working with colleagues in Seattle, last year worked out the details of how Myc cranks up the rate of growth of dividing cancer cells by sending one of the cell's factories into overdrive. In cancer, cells divide uncontrollably.

The California team based their studies on mice with genetically modified liver cells. The type of cell that becomes cancerous is called an epithelial cell, and these form cancers in breast, colon and prostate.

So the same approach might work in all of them. Liver cancer is common and difficult to treat. 

"This is a terrible cancer. Anything that is encouraging in liver cancer may be important," said Dean Felsher of Stanford University, who led the research. "The exciting thing is that you can turn cancer cells into something that appears to be normal."

The mice under study had a mutated Myc gene that was constantly on. It produced a Myc protein that served as a kind of conductor, sending a signal to cells to divide. Cancer cells produce too much Myc protein all the time, and are constantly dividing.

Dr Felsher and his colleagues fed the mice an antibiotic called doxycycline, which turned the gene off, and stopped the protein flow.

As long as the mice had the antibiotic diet, they remained healthy. Once the antibiotic was withheld, they developed aggressive liver cancer in 12 weeks. 

When they were put back on the diet, all of them showed rapid regression: the liver cancer was eliminated, and liver cells seemed to behave normally.

In effect, the scientists turned the Myc gene on and off like a tap, and turned cancer on and off at the same time.

They also found that some of the apparently normal cells retained the ability to become cancerous, which could explain why cancers often recur after chemotherapy.

Cancer hits one person in three, and kills one in five. In recent years, researchers have concentrated on a number of new approaches. They have tried to cut off the blood supply to tumours, to halt their growth.

They have tested search-and-destroy toxins, designed to make for and eliminate only cancerous cells. They have experimented with scalpels made of ultrasound, and they have tried to "burn" cancerous cells with infrared radiation.

But cancer is, above all, a disease of the DNA, and British researchers have launched a cancer genome project to collect all the genetic mutations involved in the making of a cancer. There are more than 100.

But the Myc protein seems to play a role in many cases of the disease.

The Glasgow study immediately suggested that it would be a good target. If researchers could find a drug that blocked the action of Myc, they could study its effect on cancer cases. The Stanford study shows that they were right.

But what works in mice may not work so well in humans.

The next step is to hunt for a drug that would be safe for human patients, and yet have the same impact.


Int J Cancer. 2004 Jun 20;110(3):336-42.

Reversible lymphomagenesis in conditionally c-MYC expressing mice.

Marinkovic D, Marinkovic T, Mahr B, Hess J, Wirth T.

Department of Physiological Chemistry, Ulm University, Ulm, Germany.

It is well documented that deregulation of MYC leads to tumor development, yet many aspects of this process are only partially understood. We have established a transgenic mouse model in which c-MYC is conditionally expressed in lymphoid cells using the tetracycline-regulated system of gene regulation.

Mice with continuously expressed transgenic c-MYC died of invasive T- or B-cell lymphomas within 4 months. Lymphomas developing in transgenic mice were c-MYC dependent since doxycycline treatment led to tumor regression. Using transplantation of established tumor cell lines labeled with GFP, we followed the fate of neoplastic cells in recipients upon MYC inactivation.

This approach allowed us to elucidate both apoptosis and differentiation as mechanisms of tumor elimination. Comparative genomic hybridization (CGH) and FISH analyses were performed in order to analyze possible chromosomal aberrations induced by c-MYC. We observed that overexpression of c-MYC is sufficient to induce recurrent patterns of genomic instability.

The main observation was a gain of genomic material that corresponded to chromosome 15 in several T-cell tumors, which could be identified as trisomy. Copyright 2004 Wiley-Liss, Inc.

PMID: 15095297 [PubMed - indexed for MEDLINE]


Virology. 1999 Jan 20;253(2):193-207.

Conditional cell transformation by doxycycline-controlled expression of the MC29 v-myc allele.

Oberst C, Hartl M, Weiskirchen R, Bister K.

Institute of Biochemistry, University of Innsbruck, Peter-Mayr-Str. 1a, Innsbruck, A-6020, Austria.

To investigate the molecular basis of oncogenesis induced by the v-myc oncogene of avian myelocytomatosis virus MC29, we developed a conditional cell transformation system in which expression of the MC29 v-myc allele is dependent on a doxycycline-sensitive transactivator (tTA). 

Clonal lines of quail embryo fibroblasts transformed by doxycycline-controlled v-myc revert to the normal phenotype and lose their ability to grow in soft agar after the addition of doxycycline.

Repression of v-myc causes the cells to withdraw from the cell cycle, and long-term survival in culture requires reexpression of v-myc. Although complete repression of v-myc mRNA and v-Myc protein in these cells occurs within 14 h after the addition of doxycycline, the first morphological alterations are observed after 24 h, and after 3 days, the morphology changed entirely from small rounded cells showing a typical myc-transformed phenotype to large flat cells resembling normal fibroblasts.

Cells exposed to doxycycline for 3 days reexpressed v-myc within 24 h after withdrawal of the drug from the culture medium, partial retransformation occurred after 2 days, and complete morphological transformation was reestablished after 6 days.

Analogous results were obtained with a cell line in which expression of the v-myc allele is dependent on a reverse transactivator (rtTA) that is activated by doxycycline. The striking differential expression of known transformation-sensitive genes and of new candidate v-myc target genes revealed the tightness of the doxycycline-controlled v-myc expression system.

The data also indicate that expression of v-myc in these cells is indispensable for enhanced proliferation, transformation, and immortalization. Copyright 1999 Academic Press.

PMID: 9918878 [PubMed - indexed for MEDLINE]


Partial List of Cancer-Doxy Studies


Pharmacol Res. 2011 Feb;63(2):146-50. Epub 2010 Nov 18.

Chemically modified non-antimicrobial tetracyclines are multifunctional drugs against advanced cancers.

Lokeshwar BL.

Department of Urology and Radiation Oncology, Campus Box M-800, Leonard Miller School of Medicine, University of Miami, PO Box 016960, Miami, FL 33101, United States.


Metastatic cancers account for more than 90% of cancer mortality. The metastasis of all cancers is critically mediated by enzymes that degrade extracellular matrix. Aggressive tumors are characterized by an imbalance between enzymes that degrade ECM and endogenous inhibitors of the enzymes. Matrix metalloproteinases (MMPs) make up the majority of ECM degrading enzymes implicated in cancer metastasis. The potent MMP inhibitory activities of tetracyclines, especially their chemically modified analogs, combined with their relatively well tolerated pharmacological profile, led several researchers to investigate their anticancer potential in a variety of cancers, including melanoma, lung, breast and prostate cancers. Chemically modified non-antibiotic tetracyclines (CMTs or COL) were tested using tumors of prostate, breast and melanomas. Some of these CMTs, notably, CMT-3 and CMT-308 significantly inhibited not only invasive potential and MMP activity, but also inhibited cell proliferation by inducing cell cycle arrest and apoptosis. CMT-3 and CMT-308 were significantly more potent than doxycycline or minocycline in inhibiting tumor cell-derived MMPs and inducing apoptosis in vitro and in vivo. CMT-3 (COL-3) showed potent inhibition of tumor growth in xenografts and in bone metastatic models of prostate cancer. Similar results were also reported in melanoma and breast cancer models. The mechanism by which CMTs kill tumor cells is via generation of hydroxyl free radicals ([OH](-)) which permeate and depolarize mitochondria, which in turn activates caspase mediated apoptosis. Analysis of tumor tissues from CMT-3 treated rats demonstrated reduction in angiogenesis and increase in apoptosis; both emerged as mechanisms of CMT action. These observations led to testing the efficacy of CMT-3 in human clinical trials against several types of cancer with significant outcomes, which are described in the next chapter of this issue.

Published by Elsevier Ltd.

PMID: 21093590 [PubMed - in process]PMCID: PMC3031750 [Available on 2012/2/11



Oncogene. 2011 Mar 24;30(12):1402-12. Epub 2010 Nov 15.

Inhibition of NF-kappa B activity in mammary epithelium increases tumor latency and decreases tumor burden.

Connelly L, Barham W, Onishko HM, Sherrill T, Chodosh LA, Blackwell TS, Yull FE.

1] Department of Cancer Biology, Vanderbilt University, Nashville, TN, USA [2] Department of Pharmaceutical Sciences, College of Pharmacy, University of Hawaii at Hilo, Hilo, HI, USA.


The transcription factor nuclear factor kappa B (NF-κB) is activated in human breast cancer tissues and cell lines. However, it is unclear whether NF-κB activation is a consequence of tumor formation or a contributor to tumor development. We developed a doxycycline (dox)-inducible mouse model, termed DNMP, to inhibit NF-κB activity specifically within the mammary epithelium during tumor development in the polyoma middle T oncogene (PyVT) mouse mammary tumor model. DNMP females and PyVT littermate controls were treated with dox from 4 to 12 weeks of age. We observed an increase in tumor latency and a decrease in final tumor burden in DNMP mice compared with PyVT controls. A similar effect with treatment from 8 to 12 weeks indicates that outcome is independent of effects on postnatal virgin ductal development. In both cases, DNMP mice were less likely to develop lung metastases than controls. Treatment from 8 to 9 weeks was sufficient to impact primary tumor formation. Inhibition of NF-κB increases apoptosis in hyperplastic stages of tumor development and decreases proliferation at least in part by reducing Cyclin D1 expression. To test the therapeutic potential of NF-κB inhibition, we generated palpable tumors by orthotopic injection of PyVT cells and then treated systemically with the NF-κB inhibitor thymoquinone (TQ). TQ treatment resulted in a reduction in tumor volume and weight as compared with vehicle-treated control. These data indicate that epithelial NF-κB is an active contributor to tumor progression and demonstrate that inhibition of NF-κB could have a significant therapeutic impact even at later stages of mammary tumor progression.

PMID: 21076466 [PubMed - in process]PMCID: PMC3063854 [Available on 2011/9/24]


Br J Pharmacol. 2010 Jul;160(5):1171-84.

Activation of c-Jun N-terminal kinase is essential for mitochondrial membrane potential change and apoptosis induced by doxycycline in melanoma cells.

Shieh JM, Huang TF, Hung CF, Chou KH, Tsai YJ, Wu WB.

Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan.


BACKGROUND AND PURPOSE: Tetracyclines were recently found to induce tumour cell death, but the early processes involved in this cytotoxic effect remain unclear.

EXPERIMENTAL APPROACH: Viability of human and mouse melanoma cells was determined by MTT assay and flow cytometry. Kinase/protein/caspase activation was measured by Western blotting and mitochondrial membrane potential (DeltaPsi(m)) was analyzed by fluorescence microscopy and flow cytometry.

KEY RESULTS: Human and mouse melanoma cells were treated with doxycycline or minocycline but only doxycycline was cytotoxic. This cell death (apoptosis) in A2058 cells involved activation of caspase-3, -7 and -9 and contributed to inhibition, by doxycycline, of matrix metalloproteinase (MMP) activity and migration of these cells. Doxycycline induced intra-cellular reactive oxygen species (ROS) production, apoptosis signal-regulated kinase 1 (ASK1), c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) activation at an early stage of treatment and induced mitochondrial cytochrome c release into cytosol and DeltaPsi(m) change during apoptosis. The JNK inhibitor/small interference RNA inhibited doxycycline-induced JNK activation, DeltaPsi(m) change and apoptosis, but did not affect ASK1 activation, suggesting a role of ASK1 for JNK activation in melanoma cell apoptosis. Two ROS scavengers reduced doxycycline-induced JNK and caspase activation, and apoptosis. Taken together, the results suggest the involvement of a ROS-ASK1-JNK pathway in doxycycline-induced melanoma cell apoptosis.

CONCLUSIONS AND IMPLICATIONS: We have shown a promising cytotoxic effect of doxycycline on melanoma cells, have identified ROS and ASK1 as the possible initiators and have demonstrated that JNK activation is necessary for doxycycline-induced melanoma cell apoptosis.

PMID: 20590610 [PubMed - indexed for MEDLINE]PMCID: PMC2936026 [Available on 2011/7/1]



Mol Cancer. 2010 Sep 23;9:258.

Runx2 transcriptome of prostate cancer cells: insights into invasiveness and bone metastasis.

Baniwal SK, Khalid O, Gabet Y, Shah RR, Purcell DJ, Mav D, Kohn-Gabet AE, Shi Y, Coetzee GA, Frenkel B.

Department of Biochemistry & Molecular Biology, University of Southern California, Los Angeles, CA, USA.


BACKGROUND: Prostate cancer (PCa) cells preferentially metastasize to bone at least in part by acquiring osteomimetic properties. Runx2, an osteoblast master transcription factor, is aberrantly expressed in PCa cells, and promotes their metastatic phenotype. The transcriptional programs regulated by Runx2 have been extensively studied during osteoblastogenesis, where it activates or represses target genes in a context-dependent manner. However, little is known about the gene regulatory networks influenced by Runx2 in PCa cells. We therefore investigated genome wide mRNA expression changes in PCa cells in response to Runx2.

RESULTS: We engineered a C4-2B PCa sub-line called C4-2B/Rx2 dox, in which Doxycycline (Dox) treatment stimulates Runx2 expression from very low to levels observed in other PCa cells. Transcriptome profiling using whole genome expression array followed by in silico analysis indicated that Runx2 upregulated a multitude of genes with prominent cancer associated functions. They included secreted factors (CSF2, SDF-1), proteolytic enzymes (MMP9, CST7), cytoskeleton modulators (SDC2, Twinfilin, SH3PXD2A), intracellular signaling molecules (DUSP1, SPHK1, RASD1) and transcription factors (Sox9, SNAI2, SMAD3) functioning in epithelium to mesenchyme transition (EMT), tissue invasion, as well as homing and attachment to bone. Consistent with the gene expression data, induction of Runx2 in C4-2B cells enhanced their invasiveness. It also promoted cellular quiescence by blocking the G1/S phase transition during cell cycle progression. Furthermore, the cell cycle block was reversed as Runx2 levels declined after Dox withdrawal.

CONCLUSIONS: The effects of Runx2 in C4-2B/Rx2 dox cells, as well as similar observations made by employing LNCaP, 22RV1 and PC3 cells, highlight multiple mechanisms by which Runx2 promotes the metastatic phenotype of PCa cells, including tissue invasion, homing to bone and induction of high bone turnover. Runx2 is therefore an attractive target for the development of novel diagnostic, prognostic and therapeutic approaches to PCa management. Targeting Runx2 may prove more effective than focusing on its individual downstream genes and pathways.

PMID: 20863401 [PubMed - indexed for MEDLINE]PMCID: PMC2955618



J Natl Cancer Inst. 2010 Sep 8;102(17):1322-35. Epub 2010 Aug 23.

Overexpression and activation of the alpha9-nicotinic receptor during tumorigenesis in human breast epithelial cells.

Lee CH, Huang CS, Chen CS, Tu SH, Wang YJ, Chang YJ, Tam KW, Wei PL, Cheng TC, Chu JS, Chen LC, Wu CH, Ho YS.

Graduate Institute of Biomedical Technology, Taipei Medical University, No. 250 Wu-Hsing Street, Taipei, Taiwan.

Comment in:            J Natl Cancer Inst. 2010 Sep 8;102(17):1298-9.


BACKGROUND: Large epidemiological cohort studies in the United States have indicated that active and passive smoking are associated with increased breast cancer risk. However, there was no direct evidence of an effect of tobacco carcinogens on the cellular molecules involved in breast tumorigenesis.

METHODS: Reverse transcription-polymerase chain reaction was used to determine the expression of all of the nicotinic acetylcholine receptor (nAChR) subunits in 50 human breast cancer samples and to determine the expression of the alpha9-nAChR subunit in 276 surgical and laser capture microdissected breast tumor vs normal tissue pairs. Stable MDA-MB-231 breast cancer cell lines were established in which expression of the alpha9-nAChR subunit was inhibited using short interfering RNA. MCF-10A normal human breast epithelial cells were established in which the alpha9-nAChR subunit could be conditionally overexpressed by removal of doxycycline from the culture fluid. Cell proliferation and soft agar assays and tumor growth in nude mice were used as measures of cell transformation. All statistical tests were two-sided.

RESULTS: In 186 (67.3%) of the 276 paired samples, alpha9-nAChR mRNA was expressed at (mean 7.84-fold) higher levels in breast cancers than in surrounding normal tissue. Stable expression of alpha9-nAChR short interfering RNA in MDA-MB-231 cells attenuated nicotine-stimulated proliferation and growth in soft agar and reduced tumor volume when the cells were introduced as xenografts in SCID mice (n = 5 mice per group; mean tumor volume at 6 weeks treatment in mice injected with Si alpha9 cells = 995.6 mm(3), in mice injected with parental cells = 2993.2 mm(3), difference = 1997.6 mm(3), 95% confidence interval [CI] = 1705 to 2290.2 mm(3), P = .009). Long-term treatment of MCF-10A normal breast epithelial cells with either nicotine or its active metabolite, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone, triggered precancerous transformation as defined by soft agar assay. Inducible overexpression of alpha9-nAChR in MCF-10A cell xenografts in nude mice substantially increased tumor growth (n = 5 mice per group; DOX+, mean tumor volume without nicotine vs with nicotine = 266.2 vs 501.6 mm(3), difference = 235.4 mm(3), 95% CI = 112.7 to 358 mm(3), P = .009; DOX-, mean tumor volume without nicotine vs with nicotine = 621.2 vs 898.6 mm(3), difference = 277.4 mm(3), 95% CI = 98.1 to 456.7 mm(3), P = .016; mean tumor volume in the presence of nicotine, DOX+ vs DOX- = 501.6 vs 898.6 mm(3), difference = 397 mm(3), 95% CI = 241.3 to 552.6 mm(3), P = .009).

CONCLUSION: The alpha9-nAChR is important for nicotine-induced transformation of normal human breast epithelial cells.

PMID: 20733118 [PubMed - indexed for MEDLINE]


Am J Physiol Lung Cell Mol Physiol. 2010 Sep;299(3):L393-400. Epub 2010 Jun 25.

Effect of doxycycline on proliferation, MMP production, and adhesion in LAM-related cells.

Chang WY, Clements D, Johnson SR.

Division of Therapeutics and Molecular Medicine and Respiratory Biomedical Research Unit, University of Nottingham, Queen's Medical Centre, Nottingham, NG7 2UH United Kingdom.


Matrix metalloproteinases (MMPs) have been implicated in lung cyst formation in lymphangioleiomyomatosis (LAM). As doxycycline inhibits MMP activity in vivo, some patients take doxycycline, as one report has suggested a possible benefit in LAM. However, there have been no randomized controlled clinical trials of doxycycline for LAM, and any mechanism of action is unclear. Here, we examine previously proposed mechanisms of actions. Cell proliferation and adhesion were examined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction and Cytomatrix cell adhesion kits. Apoptosis was examined by TdT-mediated dUTP nick end labeling (TUNEL) assay. MMP-2 expression was examined by quantitative real-time PCR and zymography in doxycycline-treated ELT3 cells and tumor growth using angiomyolipoma-derived tumor xenografts in nude mice. In ELT3 cells, >or=25 microg/ml doxycycline decreased proliferation, increased apoptosis, and caused a change in cell morphology associated with redistribution of actin stress filaments. Reduction in proliferation was also seen in human angiomyolipoma-derived cells. Cell adhesion to ECM proteins was decreased by doxycycline at 50 microg/ml and prevented detachment of already adherent cells. There was no effect of doxycycline on MMP-2 expression or activity in vitro. In the xenograft model, doxycycline (30 mg*kg(-1)*day(-1)) had no effect on tumor growth, final tumor weight, or tumor lysate MMP levels. Doxycycline at doses >or= 25 microg/ml inhibited cell proliferation and adhesion, possibly by a toxic effect. Doxycycline had no effect on MMP-2 expression or activity or tumor growth in the xenograft model. Any possible in vivo effect is unlikely to be mediated by MMP-2 or reduced cell proliferation.

PMID: 20581100 [PubMed - indexed for MEDLINE]


Glia. 2010 Aug;58(10):1145-56.

Disruption of transient receptor potential canonical channel 1 causes incomplete cytokinesis and slows the growth of human malignant gliomas.

Bomben VC, Sontheimer H.

Department of Neurobiology, Center for Glial Biology in Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.


Despite decades of research, primary brain tumors, gliomas, lack effective treatment options and present a huge clinical challenge. Particularly, the most malignant subtype, Glioblastoma multiforme, proliferates extensively and cells often undergo incomplete cell divisions, resulting in multinucleated cells. We now present evidence that multinucleated glioma cells result from the functional loss of transient receptor potential canonical 1 (TRPC1) channels, plasma membrane proteins involved in agonist-induced calcium entry and reloading of intracellular Ca(2+) stores. Pharmacological inhibition or shRNA mediated suppression of TRPC1 causes loss of functional channels and store-operated calcium entry in D54MG glioma cells. This is associated with reduced cell proliferation and, frequently, with incomplete cell division. The resulting multinucleated cells are reminiscent of those found in patient biopsies. In a flank tumor model, tumor size was significantly decreased when TRPC1 expression was disrupted using a doxycycline inducible shRNA knockdown approach. These results suggest that TRPC1 channels play an important role in glioma cell division most likely by regulating calcium signaling during cytokinesis.

(c) 2010 Wiley-Liss, Inc.

PMID: 20544850 [PubMed - indexed for MEDLINE]




Bb and cancer and Armed Forces Inst. of Pathology senior scientist S-C Lo's patent on M. fermentans work on M. fermentans and breast and ovarian cancer progression and metastasis (see abstract of AAEM presentation below).

American Academy of Environmental Medicine 2005 Annual Meeting 

Association of Mycoplasmal Infections with Malignant Progression, Relapse and Stage in Breast Cancer Patients 

Prof. Garth L. Nicolson The Institute for Molecular Medicine, Huntington Beach, CA Email: Intracellular bacterial infections have historically been proposed as acause of cancer [1,2].  Although bacterial involvement in malignant transformation and its reversal with antibiotic treatment have been demonstrated in animal models [3], there are few examples of direct involvement of bacteria in clinical transformation of malignant cells [4].  

It seems more likely that the release of Reactive Oxygen Species (ROS) and other genotoxic molecules by intracellular bacteria play a role in progression to malignancy rather than the inception of cancer or transformation [5].  

Reports in the literature indicate that over one-half of ovarian cancer patients have mycoplasmal infections in their tumors [6], and the incidence of infection in ovarian cancer was related to stage and survival [7].  Some results have been questioned on the basis of contamination in tissue culture [8], but most studies did not use culture procedures.  Therefore, we examined breast cancer patients to determine if there was a relationship between systemic mycoplasmal infections and progression of their breast cancers.  

Examination of breast cancer patients showed mycoplasmal infections inside blood leukocytes (~50%+) not blood plasma or serum.  The most common species found were M. fermentans, M. pneumoniae and M. genitalium.  In contrast, in healthy adults the incidenceof these species was low [9].  

We found an association between stage, progression (measured by relapse after surgery) and presence of mycoplasmal infection(s) (P<0.001) in breast cancer.  The results suggest that intracellular mycoplasmal infections known to be associated with malignant progression are significantly related to progression and relapse due to metastasis of breast cancer. 

References 1. Nuzum JW. Surg Gynecol Obstet 1925; 11:343-353. 2. Plata et al. J Infect Dis 1973; 128:588-598 3. Tsai et al. PNAS 1995; 92:10197-10201. 4. Feng et al. Mol Cell Biol 1999; 19:7995-8002. 5. Nicolson GL. JANA 2003; 6(3):22-28. 6. Chan et al. Gynecol Oncol. 1996; 63(2):258-260. 7. Camolai N. Can J Microbiol 2001; 47(8):691-697. 8. Quirk et al. Gynecol Oncol. 2001; 83(3):560-562. 9. Nicolson  et al.  J Chronic Fatigue Syndr 2000; 6(3):23-39.,242,820.PN.&OS=PN/5,242,820&RS=PN/5,242,820# 

Patent Number: 5,242,820 is the US DOD patent on Mycoplasma


Therapie. 2014 Mar-Apr;69(2):129-41. doi: 10.2515/therapie/2013069. Epub 2014 Jun 12.

[Doxycycline or how to create new with the old?].

[Article in French]


Tetracyclines are broad-spectrum antibiotics that interfere with protein synthesis. They were first widely prescribed by dermatologists in the early 1950s in the treatment of acne. More recently, their biological actions on inflammation, proteolysis, angiogenesis, apoptosis, metal chelation, ionophoresis, and bone metabolism were studied. Matrix metalloproteinases (MMPs) are a family of proteolytic enzymes that degrade components of the extracellular matrix (ECM). MMPs have direct or indirect effects on the vascular endothelium and the vascular relaxation/contraction system. The therapeutic effects of tetracyclines and analogues were studied in rosacea, bullous dermatoses, neutrophilic diseases, pyoderma gangrenosum, sarcoidosis, aortic aneurysms, cancer metastasis, periodontitis and autoimmune diseases autoimmune diseases such as rheumatoid arthritis and scleroderma. In addition, downregulation of MMP using doxycyclinecould be beneficial in reducing vascular dysfunction mediated by MMPs and progressive damage of the vascular wall. We review the nonantibiotic properties of doxycycline and its potential clinical applications. 

© 2014 Société Française de Pharmacologie et de Thérapeutique.

[PubMed - indexed for MEDLINE] 

Nat Commun. 2014 Mar 19;5:3485. doi: 10.1038/ncomms4485.

Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction.


We recently identified endotrophin as an adipokine with potent tumour-promoting effects. However, the direct effects of local accumulation of endotrophin in adipose tissue have not yet been studied. Here we use a doxycycline-inducible adipocyte-specific endotrophin overexpression model to demonstrate that endotrophin plays a pivotal role in shaping a metabolically unfavourable microenvironment in adipose tissue during consumption of a high-fat diet (HFD). Endotrophin serves as a powerful co-stimulator of pathologically relevant pathways within the 'unhealthy' adipose tissue milieu, triggering fibrosis and inflammation and ultimately leading to enhanced insulin resistance. We further demonstrate that blocking endotrophin with a neutralizing antibody ameliorates metabolically adverse effects and effectively reverses metabolic dysfunction induced during HFD exposure. Collectively, our findings demonstrate that endotrophin exerts a major influence in adipose tissue, eventually resulting in systemic elevation of pro-inflammatory cytokines and insulin resistance, and the results establish endotrophin as a potential target in the context of metabolism and cancer

[PubMed - indexed for MEDLINE] 
Free PMC Article
Link Here

Int J STD AIDS. 2013 Jun;24(6):501-2. doi: 10.1177/0956462412472805. Epub 2013 Jul 9.

False-positive prostate cancer markers in a man with symptomatic urethral Chlamydia trachomatis infection.

Author information

  • 1Department of Laboratory Medicine, Karolinska Institutet, Stockholm, Sweden.


Symptomatic male urethral Chlamydia trachomatis infection resulted in inflammation of the prostate, with associated increases in both prostate-specific (PSA) and prostate cancer-specific (PCA3) markers with prostate biopsies showing no evidence of malignancy.


Chlamydia trachomatis; HPV; PCA3; PSA; prostate cancer markers; prostatitis

[PubMed - indexed for MEDLINE]

Mikrobiyol Bul. 2009 Jul;43(3):493-7.

[A case of Brucella prostatitis misdiagnosed as prostate carcinoma].

[Article in Turkish]


Brucellosis is a major public health problem in Turkey and all over the world. Joint pain, night sweats, anorexia, weakness, loss of weight and headache are the basic symptoms of brucellosis and the illness can affect many organs. Genitourinary involvement is reported in 2-20% of cases, epididimoorchitis being the most frequent complication, however, prostatic involvement is far more uncommon. In this paper, a case of Brucella prostatitis misdiagnosed as prostate carcinoma has been presented. A 50-years-old man who was a microbiology laboratory staff has been admitted to our outpatient clinic with the complaints of joint pain, weakness, fever, urgency, difficulty and pain during urination. Since prostate specific antigen (PSA) was 23.6 ng/ml (normal value < 4 ng/ml) and free PSA (fPSA) was 3.89 ng/ml (normal value < 1 ng/ml), needle biopsy from the prostate was performed. Blood cultures performed by BACTEC 9200 (Becton Dickinson, Sparks, Md.) system yielded Brucella melitensis, and the pathological examination of the prostate biopsy revealed prostatic hyperplasia and prostatitis. Brucella standard tube agglutination titer was 1/320. Upon the diagnosis of Brucella prostatitis the patient was treated with a combination of 200 mg doxycycline and 600 mg rifampicin daily for 6 months. During the follow-up period no complication was detected in the patient and the PSA level decreased to 1.57 ng/ml and fPSA to 0.43 ng/ml. This case was reported to withdraw attention to prostatic involvement during brucellosis. Elevated PSA values with the signs and symptoms of brucellosis in endemic areas should be evaluated accordingly and appropriate therapy should be initiated without any delay.

[PubMed - indexed for MEDLINE] 

J Am Acad Dermatol. 2006 Feb;54(2):258-65.

Tetracyclines: nonantibiotic properties and their clinical implications.

Author information

  • 1Department of Dermatology, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.


Tetracyclines are broad-spectrum antibiotics that act as such at the ribosomal level where they interfere with protein synthesis. They were first widely prescribed by dermatologists in the early 1950s when it was discovered that they were effective as a treatment for acne. More recently, biologic actions affecting inflammation, proteolysis, angiogenesis, apoptosis, metal chelation, ionophoresis, and bone metabolism have been researched. The therapeutic effects of tetracycline and its analogues in various diseases have also been investigated. These include rosacea, bullous dermatoses, neutrophilic diseases, pyoderma gangrenosum, sarcoidosis, aortic aneurysms, cancer metastasis, periodontitis, and autoimmune disorders such as rheumatoid arthritis and scleroderma. We review the nonantibiotic properties of tetracycline and its analogues and their potential for clinical application.

[PubMed - indexed for MEDLINE]

shopify visitor statistics