Probiotic-based Chemotherapy (PCT) targeting cancer stem cells and immune-inhibitory receptors in metastatic breast cancer and in other advanced metastatic cancers: A pharmaceutical mixture encompassing Acarbose [trade name: Glucobay, Precose, Prandase]and probiotic Lactobacillus rhamnosus (ALR) increases the expression of tumor suppressor genes, such as TPM1(Tropomycin1), TIMP3 (TIMP Metallopeptidase Inhibitor 3),  p53, and TA-p73/p63, inhibits immune-inhibitory receptors/molecules, targets cancer stem cells, confers protection against chemoresistance and prolongs survival, and stalls metastatic breast cancer progression, via up-regulation of its target gene, 16/January/2019, 12.11 am

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What we say:

Dr L Boominathan PhD, the Director-cum-chief Scientist of GBMD, reports that: Probiotic-based Chemotherapy (PCT) targeting cancer stem cells and immune-inhibitory receptors in metastatic breast cancer and in other advanced metastatic cancers: A pharmaceutical mixture encompassing Acarbose [trade name: Glucobay, Precose, Prandase]and probiotic Lactobacillus rhamnosus (ALR) increases the expression of tumor suppressor genes, such as TPM1(Tropomycin1), TIMP3 (TIMP Metallopeptidase Inhibitor 3),  p53, and TA-p73/p63, inhibits immune-inhibitory receptors/molecules, targets cancer stem cells, confers protection against chemoresistance and prolongs survival, and stalls metastatic breast cancer progression, via up-regulation of its target gene, 16/January/2019, 12.10 pm


The Significance of the study to Public health relevance:

First, given that: (i) each year nearly 14 million people–more than 2 50,000 patients are diagnosed with breast cancer ever year in the US– are diagnosed with cancer globally, and little more than half of them will die due to lack of curative treatment available at present; (ii) cancer deaths globally are expected to be doubled by 2030;  and (iii) cancer causes the highest economic loss compared to all the known causes of death worldwide, there is an urgent need to find: (i) a way to prevent an individual from being susceptible to cancer by strengthening his/her own immune system (Cancer immunotherapy); (ii) a cheaper alternative to the existing expensive anticancer drugs; (iii) a side-effect-free natural product-based anticancer drugs that target cancer stem cells; and (iv) a way to effectively treat and prevent metastatic progression and relapse of ovarian cancers.

Second, given that: (1) cancer suppressor p53 is mutated in more than 50% of human cancers of different tissue origin; (2) p53 pathway is altered in about 80% of tumors; (3) our understanding is incomplete in terms of molecular targets and the oncogenic/malignant pathways involved in mutant p53-overexpressing tumors; (4) cancer causes the highest economic loss compared to all the known causes of death worldwide; and (5) cancer causes the considerable economic loss worldwide, there is an urgent need to find a way to effectively treat and stall metastatic progression and relapse of mutant p53-overexpressing human cancers.


From research findings to therapeutic opportunity :

(i) Therapeutic strategy:

This study suggests a therapeutic strategy for stalling the progression of p53-deficient/deleted or mutant-p53 expressing metastatic breast cancers. By activating tumor suppressor p53’s unmutated “homologous protein such as TAp73/p63” in p53-deficient or mutant-p53 expressing metastatic cancer cells, one can stall their progression.

(ii) Research findings: This study presented here suggests, for the first time, that a pharmacological formulation encompassing Acarbose (trade name: Glucobay, Precose, Prandase), by increasing the expression of its target genes, it may: (i) decrease the expression of a number of oncogenes and DNA repair proteins; (ii) increase the expression of tumor/metastasis suppressor genes, such as TPM1(Tropomycin1), and TIMP3 (TIMP Metallopeptidase Inhibitor 3); (iii) increase the expression of a number of other tumor suppressor genes, including p53/TA-p73/p63, and their target genes, INKa, p19ARF and others (Figure 1);(iv) activate tumor/metastasis suppressor network; (v) inhibit immunosuppressive/immune-inhibitory receptors/ molecules; (vi) inhibit the activity and proliferation of cancer stem cells; (vii) inhibit tumor growth; and (viii) promote survival (Figures 1-4). Further, the efficacy of Acorbose can be increased by treating cancer patients with probiotic Lactobacillus rhamnosus  (1.0×103 CFU/ml).

Figure 1. Mechanistic insights into how a pharmacological formulation encompassing Acarbose and Lactobacillus Rhamnosus (ALR) increases the expression of tumor/metastatic suppressors, such as TPM1, TIMP3, p53, TAp73/p63, INK4a, p19ARF and others, inhibits the expression of immune-inhibitory receptors, stops the proliferation of cancer stem cells, and stalls the progression of advanced metastatic cancers.

Figure 2 A pharmacological formulation encompassing Acarbose and Lactobacillus Rhamnosus (ALR) may not only function as a tumor/metastatic suppressors agent in advanced metastatic cancers,  but also in mutant-p53 expressing human cancers.

Figure 4. A pharmacological formulation encompassing Acarbose and Probiotic Lactobacillus rhamnosus(ALR) may attenuate the progression of advanced  metastatic cancers, including metastatic breast cancer, through induction of tumor/metastatic suppressors, such as TPM1, TIMP3, p53, TAp73/p63, INK4a, p19ARF and others

Thus, a pharmacological formulation encompassing “Acarbose or its analogs/mechanistic functional equivalents” either alone or in combination with other known anti-cancer/metabolic drugs, or probiotics enriched with anti-cancer activity, such as  Lactobacillus rhamnosus,” may be used to inhibit the progression of advanced  cancers, including metastatic breast cancer, and thereby promote disease-free survival (Figure 3-4).

Details of the Research findings:

Idea Proposed/Formulated (with experimental evidence) by: Dr L Boominathan Ph.D.

Amount: $1, 500#

Undisclosed mechanistic information: How does a pharmacological formulation encompassing Acarbose increase the expression of tumor/metastatic suppressors TPM1 and TIMP3?

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References:

Web: http://genomediscovery.org or http://newbioideas.com/

Citation: Boominathan, L., Probiotic-based Chemotherapy (PCT) targeting cancer stem cells and immune-inhibitory receptors in metastatic breast cancer and in other advanced metastatic cancers: A pharmaceutical mixture encompassing Acarbose [trade name: Glucobay, Precose, Prandase]and probiotic Lactobacillus rhamnosus (ALR) increases the expression of tumor suppressor genes, such as TPM1(Tropomycin1), TIMP3 (TIMP Metallopeptidase Inhibitor 3),  p53, and TA-p73/p63, inhibits immune-inhibitory receptors/molecules, targets cancer stem cells, confers protection against chemoresistance and prolongs survival, and stalls metastatic breast cancer progression, via up-regulation of its target gene, 16/January/2019, 12.11 am, Genome-2-BioMedicine Discovery center (GBMD), http://genomediscovery.org

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