Out of options? Then you could try this

Felixthecat
Felixthecat Member Posts: 37
edited March 2014 in Colorectal Cancer #1
The drug referred to below is only available via the FMFs Compassionate Use Program so if other treatments are unsuccessful you could contact them and try it. It is a hormone antagonist and quite well tolerated as meds go:

Their website link is:
http://feminist.org/rrights/compassionateuse.asp


2004: Effects of mifepristone on proliferation of human gastric adenocarcinoma cell line SGC-7901 in vitro.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15309708&itool=iconfft&query_hl=20&itool=pubmed_docsum
Mifepristone effectively inhibited the proliferation of PR-positive human gastric adenocarcinoma cell line SGC-7901 in vitro through multiple mechanisms, and may be a beneficial agent against human adenocarcinoma

2004: (Detailed article) Reversal of multidrug resistance in drug-resistant human gastric cancer cell line SGC7901/VCR by antiprogestin drug mifepristone
http://www.thymic.org/thypdf/biol/mif2.pdf


2004: Reversal of multidrug resistance in drug-resistant human gastric cancer cell line SGC7901/VCR by antiprogestin drug mifepristone
http://www.wjgnet.com/1007-9327/abstract_en.asp?v=10&f=1722
Mifepristone has potent reversal effect on MDR in SGC7901/VCR via inhibiting the function of MRP and P-gp, modulating the expression of Bcl-2 and Bax proteins, and enhancing the sensitivity to anticancer agent VCR


2004: Inhibitory effects of mifepristone on the growth of human gastric cancer cell line MKN-45 in vitro and in vivo.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15669177&itool=iconabstr&query_hl=20&itool=pubmed_docsum
Mifepristone exerts significant growth inhibitory effects on PR-positive human MKN-45 gastric cancer cells via multiple mechanisms, and may be a beneficial agent against the tumor.


2004: Effects of mifepristone on invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45 in vitro and in vivo.
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15188494&dopt=
• “Mifepristone can effectively inhibit the invasive and metastatic potential of human gastric adenocarcinoma cell line MKN-45 in vitro and in vivo through inhibition of heterotypic adhesion to basement membrane, cell migration and angiogenesis.”

2003: Glucocorticoid Cotreatment Induces Apoptosis Resistance toward Cancer Therapy in Carcinomas1
http://cancerres.aacrjournals.org/cgi/content/full/63/12/3112

GCs are widely used in high doses in the therapy of leukemias and lymphomas and are also used as antiemetics or preservatives for normal cells during chemotherapy of solid tumors. In addition, GCs are among the most widely used anti-inflammatory drugs. In this study, we have shown that application of GCs renders certain tumors resistant or less susceptible to apoptosis after cancer therapy. This finding urges to carefully reconsider the widespread use of GCs in almost all treatment protocols for patients with solid cancers. In the clinical setting of cancer therapy, e.g., in antiemetic regimens, corticosteroids are usually given transiently to suppress acute side effects of cancer therapy. Although our experiments did not mimic precisely the clinical situation because we administered DEX daily to achieve steady-state levels, short-term exposure to DEX may nevertheless be sufficient to abrogate or diminish the efficacy of concomitant chemotherapy in cancer patients in vivo. This is suggested by our experiments where DEX was found to down-regulate basal and cisplatin-induced expression of apoptosis effectors within 24 h in vitro. Also, endogenous levels of GCs and those existing as a consequence of administered hormones may render solid tumors less susceptible to apoptosis after cancer therapy. The administration of steroid/receptor agonists such as RU486 might be beneficial before chemotherapy and radiotherapy to enhance cell death of solid tumor cells

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  • Felixthecat
    Felixthecat Member Posts: 37
    Just to explain a little more - the drug is the most effective progesterone antagonist and at a higher dose a glucocorticoid antagonist (the 2 hormones are similar in structure) and colon cancers can be hormone dependant. Here's a few more research findings.

    2003: Glucocorticoid Receptor (GR) Immunohistochemical Expression Is Correlated with Cell Cycle-Related Molecules in Human Colon Cancer
    http://www.ingentaconnect.com/content/klu/ddas/2003/00000048/00000009/00473074

    ....Our findings support evidence for GR participation in the biological mechanisms underlying the carcinogenic evolution in the colon, implying the use of glucocorticoids as an adjuvant treatment for cell cycle modulation in colon cancer cells.

    2007: Androgen and progesterone receptors in colonic and rectal cancers
    http://www.springerlink.com/content/9w089j535u57pu33/

    ....Abstract Androgen, progesterone and estrogen receptors were analyzed in 12 primary colonic cancers and 16 primary rectal cancers. Androgen and progesterone receptors were positive in some colonic cancers and rectal carcinomas; however, none of the specimens analyzed showed estradiol receptor.

    2003: Glucocorticoid Cotreatment Induces Apoptosis Resistance toward Cancer Therapy in Carcinomas1
    http://cancerres.aacrjournals.org/cgi/content/full/63/12/3112

    “....In conclusion, GCs are widely used in high doses in the therapy of leukemias and lymphomas and are also used as antiemetics or preservatives for normal cells during chemotherapy of solid tumors. In addition, GCs are among the most widely used anti-inflammatory drugs. In this study, we have shown that application of GCs renders certain tumors resistant or less susceptible to apoptosis after cancer therapy. This finding urges to carefully reconsider the widespread use of GCs in almost all treatment protocols for patients with solid cancers. In the clinical setting of cancer therapy, e.g., in antiemetic regimens, corticosteroids are usually given transiently to suppress acute side effects of cancer therapy. Although our experiments did not mimic precisely the clinical situation because we administered DEX daily to achieve steady-state levels, short-term exposure to DEX may nevertheless be sufficient to abrogate or diminish the efficacy of concomitant chemotherapy in cancer patients in vivo. This is suggested by our experiments where DEX was found to down-regulate basal and cisplatin-induced expression of apoptosis effectors within 24 h in vitro. Also, endogenous levels of GCs and those existing as a consequence of administered hormones may render solid tumors less susceptible to apoptosis after cancer therapy. The administration of steroid/receptor agonists such as RU486 might be beneficial before chemotherapy and radiotherapy to enhance cell death of solid tumor cells.

    Human Glucocorticoid Receptor â Binds RU-486 and Is Transcriptionally Active
    http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1820503
    Human glucocorticoid receptor (hGR) is expressed as two alternately spliced C-terminal isoforms, á and â. In contrast to the canonical hGRá, hGRâ is a nucleus-localized orphan receptor thought not to bind ligand and not to affect gene transcription other than by acting as a dominant negative to hGRá. Here we used confocal microscopy to examine the cellular localization of transiently expressed fluorescent protein-tagged hGRâ in COS-1 and U-2 OS cells. Surprisingly, yellow fluorescent protein (YFP)-hGRâ was predominantly located in the cytoplasm and translocated to the nucleus following application of the glucocorticoid antagonist RU-486. This effect of RU-486 was confirmed with transiently expressed wild-type hGRâ. Confocal microscopy of coexpressed YFP-hGRâ and cyan fluorescent protein-hGRá in COS-1 cells indicated that the receptors move into the nucleus independently. Using a ligand binding assay, we confirmed that hGRâ bound RU-486 but not the hGRá ligand dexamethasone. Examination of the cellular localization of YFP-hGRâ in response to a series of 57 related compounds indicated that RU-486 is thus far the only identified ligand that interacts with hGRâ. The selective interaction of RU-486 with hGRâ was also supported by molecular modeling and computational docking studies. Interestingly, microarray analysis indicates that hGRâ, expressed in the absence of hGRá, can regulate gene expression and furthermore that occupation of hGRâ with the antagonist RU-486 diminishes that capacity despite the lack of helix 12 in the ligand binding domain......

    .....Taken together, this work suggests that hGRâ may have a more important physiological role than has previously been thought, both as an endogenous manipulator of gene expression and as a pharmaceutical target.(more detail via link above)