Saturday, July 20, 2013

EVERYTHING cures why do we have it??????

B saw the latest "coffee" data yesterday and it got me thinking about all the things that CURE melanoma!!!!  Now, mind you, I'm not claiming they do or they don't. The data is either too vague, too limited, or has so little to do with people that you can't tell.  AND....because there are no big bucks to be made as all of these things are pretty cheap, food, or over the counters...I don't see anybody forking over the money for study.  Oh well....for what it's worth....

COFFEE:  More than once daily...if you have the right genes, shows a "protective effect" for cutaneous melanoma.  Not sure exactly what that means, and not really clear if these genes might be the protection in and of themselves, without the addition of coffee.  Presumably they looked at that, but????

DOXYCYCLINE:  An older antibiotic, causes some nausea, but pretty good in treating acne, kills and inhibits growth of melanoma cells.

CURCUMIN:  The yellow part of curry and mustard also stops melanoma in its tracks, at least in a petri dish.

CIMETADINE:  aka: tagamet, taken for heart burn, ulcers, etc, as it decreases stomach acid, helped get rid of melanoma in at least three horses.  There's a smattering of human "data" out there, too.

NSAID's:  Non steroidal anti-iflammatory drugs like Advil seem to decrease the risk of melanoma and squamous cell skin cancers.

SHIITAKES:  Good old Lentinula edodes mycelia!  If you're a mouse with melanoma and you have access to mushroom are in luck, my friend.

THE DATA:  Read at your own risk (the stuff on NAID's and Shiitakes I've posted before)!!

The protective effect of coffee consumption on cutaneous melanoma risk and the role of GSTM1 and GSTT1 polymorphisms.
Source  Clinical Epidemiology Unit, Istituto Dermopatico dell'Immacolata, IDI-IRCSS, Via dei Monti di Creta, 104, 00167, Rome, Italy,  2013 Jul 17. [Epub ahead of print]
PURPOSES: The authors examined the association between coffee consumption and cutaneous melanoma and the implication of GSTM1 and GSTT1 polymorphisms.
METHODS: A hospital-based case-control study was conducted in the inpatient wards of IDI-San Carlo Rome, Italy, including 304 incident cases of cutaneous melanoma and 305 controls. Information on socio-demographic characteristics, medical history, smoking, sun exposure, pigmentary characteristics and diet was collected for all subjects. Within the study, individual patterns at two polymorphic genes (GSTM1 and GSTT1) belonging to glutathione S-transferases family were investigated in 188 cases of cutaneous melanoma and 152 controls. Logistic regression was the method used to estimate odds ratio and 95 % confidence intervals.
RESULTS: High frequency of coffee drinking (>once daily), compared with low-frequency consumption of coffee (≤7 times weekly) was associated with a protective effect for cutaneous melanoma (OR 0.46; 95 % CI 0.31-0.68) after adjusting for sex, age, education, hair colour, common nevi, skin phototype, and sunburn episodes in childhood. When stratified by GSTM1 and GSTT1 genotype, the protective effect of coffee was extremely high for subjects with both GSTM1 and GSTT1 null polymorphisms (OR 0.01; 95 % CI 0.0003-0.54).
CONCLUSIONS: Our results show a protective effect of coffee consumption for cutaneous melanoma, in particular for those with homozygous deletion for GSTM1 and GSTT1.

Doxycycline inhibits the adhesion and migration of melanoma cells by inhibiting the expression and phosphorylation of focal adhesion kinase (FAK). 
Sun T, Zhao N, Ni CS, Zhao XL, Zhang WZ, Su X, Zhang DF, Gu Q, Sun BC.  Source: Department of Pathology, Tianjin Medical University, Tianjin 300070, PR China.Cancer Lett. 2009 Nov. Epub 209 May 30.
Abstract:  Doxycycline has been found to induce apoptosis and to inhibit the growth of a variety of tumor cells, in addition to its use as an antibiotic. However, the mechanism of its actions, especially at the molecular level, remains unknown and needs to be resolved. A crucial step possibly lies in the early period of doxycycline administration, which leads to a series of cascading effects depicting the consequential biological action of doxycycline on tumor cells. The present study focuses on the early-stage effects of doxycycline administration, specifically at the stages of treatment (before 16h). In this paper, we report that doxycycline inhibits the adhesion and migration of melanoma cells. Afterwards, the cells undergo apoptosis (aniokis). Remarkably, doxycycline also inhibits the expression and phosphorylation of focal adhesion kinase (FAK), a protein tyrosine kinase involved in the regulation of cell adhesion and migration. We further demonstrate that doxycycline down-regulates the activities of MMP-2 and MMP-9, and its effects are stronger than those of an Integrin beta1 antibody. Finally, we suggest that doxycycline might exert its anti-tumor effects by inhibiting FAK signaling pathway. These results provide an insight into the possible mechanisms that underlie the multiple drug actions of doxycycline. The potential use of doxycycline in anti-tumor treatment is promising and warrants further studies.

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.  Source:  Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan.  Br J Pharmacol. 2010 Jul.
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.

Curcumin-induced antiproliferative and proapoptotic effects in melanoma cells are associated with suppression of IκB kinase and nuclear factor κB activity and are independent of the B-Raf/mitogen-activated/extracellular signal-regulated protein kinase pathway and the Akt pathway

Doris R. Siwak M.S., Shishir Shishodia Ph.D., Bharat B. Aggarwal Ph.D., Razelle Kurzrock M.D.†,*  Article first published online: 11 JUL 2005


BACKGROUND Nuclear factor-κB (NF-κB) plays a central role in cell survival and proliferation in human melanoma; therefore, the authors explored the possibility of exploiting NF-κB for melanoma treatment by using curcumin, an agent with known, potent, NF-κB-inhibitory activity and little toxicity in humans.

METHODS Three melanoma cell lines (C32, G-361, and WM 266-4), all of which had B-raf mutations, were treated with curcumin, and the authors assessed its effects on viability ((3-[4,5-dimethylthiazol-2-yl]2,5-diphenyltetrazolium bromide assay) and apoptosis (flow-cytometric analysis of annexin V/propidium iodide-stained cells). Curcumin-treated cells also were examined for NF-κB binding activity (electrophoretic mobility shift assay) and for the activity of its upstream regulator, IκB kinase (IKK) (immune complex kinase assay). In addition, relevant signaling, as reflected by B-Raf kinase activity (kinase cascade assay), and steady-state levels of activated, downstream effectors, as reflected by mitogen-activated signal-regulated protein kinase (MEK), extracellular signal-regulated protein kinase (ERK), and Akt phosphorylation levels (immunoblots), were assessed.

RESULTS  Curcumin treatment decreased cell viability of all 3 cell lines in a dose-dependent manner (50% inhibitory concentration = 6.1–7.7 μM) and induced apoptosis.  However, curcumin did not inhibit the activities of B-Raf, MEK, or ERK, and Akt phosphorylation was enhanced. Furthermore, in the presence of curcumin, the Akt inhibitor 1L-6-hydroxymethyl-chiro-inositol 2-[(R)-2-O-methyl-3-O-octadecylcarbonate] no longer suppressed Akt phosphorylation.

CONCLUSIONS  Curcumin has potent antiproliferative and proapoptotic effects in melanoma cells. These effects were associated with the suppression of NF-κB and IKK activities but were independent of the B-Raf/MEK/ERK and Akt pathways. Cancer 2005.

Cimetidine for treatment of melanomas in three horses.

Goetz TE, Ogilvie GK, Keegan KG, Johnson PJ.  Source:  Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois, Urbana 61801. J AM Vet Med Assoc. 1990

Abstract: Cimetidine, an H2 histamine antagonist, was used in the clinical management of progressive, multifocal melanomatosis in 3 adult gray horses. Prior to treatment, the tumors had increased rapidly in size and number in 2 horses (duration of 6 and 27 months, respectively) and slowly in the third horse (duration of 48 months). All 3 horses were treated with cimetidine (2.5 mg/kg of body weight, PO, q 8 h) for 2 months to 1 year. During treatment, the number and size of the melanomas decreased substantially (50 to 90%). The progression of the disease was halted in 2 horses and controlled in the third horse, which is still being treated with cimetidine (1.6 mg/kg, PO, q 24 h). The horses in which treatment was terminated have not been treated for 31 and 41 months, respectively, during which time the melanomas have not increased in number or size.


Nonsteroidal anti-inflammatory drugs and the risk of skin cancer:  A population-based case-control study. 

By:  Johannesdottir, Chang, Mehnert, et al.  In:  Cancer, 2012, May 29. [Epub]

Knowing that Nonsteroidal anti-inflammatory drugs ( aspirin, ibuprofen, etc.) may prevent the development of cancer by inhibiting cyclooxygenase (COX) enzymes, these folks from Denmark looked at NSAID use and the risk of squamous cell carcinoma, basal cell carcinoma, and melanoma.  They looked at all cases of those diseases from 1991 through 2009 in northern Denmark. (Squamous = 1,974, basal = 13, 316, and melanoma = 3,242).  They matched 10 population controls (n=178,655) to each case by age, gender, and county of residence.  Use of NSAIDs was noted via a prescription data base.  FINDINGS:  After a great deal of incidence rate ratios and confidence interval statistical shenanigans....they determined that "NSAID ever use compared with nonuse was associated with a decreased risk of squamous cell and melanoma, especially for long-term use and high-intensity use.  NSAID use was not associated with a reduced risk of basal cell.  All estimates of reduced risk were driven primarily by the use of nonselective NSAIDs and older COX-2 inhibitors."


Oral ingestion of Lentinula edodes mycelia mice   

From:  Cancer Science, March, 2011
By:  Tanaka, Ishikawa, Matsui, et al., The Japanese Cancer Association.

Poor little mice "were inoculated subcutaneously in the footpad with B16 melanoma and fed L.E.M. extract [shiitake mushroom juice].  Ingestion of L.E.M. extract significantly inhibited tumor growth, and this in vivo anti-tumor effect was not observed in nude mice, suggesting a T cell-dependent mechanism. In addition, ingestion of [shiitake juice] led to significant restoration of H-2K(b)-restricted and melanoma-reactive T cells in the spleen and draining lymph nodes of melanoma bearing mice....furthermore, an in vitro assay revealed than an immunosuppressive activity of CD4(+) T cells from melanoma-bearing mice was canceled by ingestion of [shiitake juice].  Our results indicate that oral ingestion of L.E.M. extract restores immune responses of class 1-restricted and melanoma-reactive CD8(+) T cells in melanoma-bearing mice, presumably by a mitigation of regulatory T cells-mediated immunosuppression."



  1. Talking about pain...=:o) I think Dr W's nurse Cabell must think I am one in her duff...I asked her in e-mail in the wee hours last night..what patient I was in our trial...I am patient number 4!! -Lynn

  2. I have bookmarked your blog, the articles are way better than other similar blogs.. thanks for a great blog!