Thank you,
Donna
Question Details
Lymphoma Rescue Chemo Case
by
Thank you,
Donna
Replies
by
August 18, 2009
Oh and forgot she has active dreaming...always has had but much more pronounced too the point of looking like seizures...
by
naturevet
August 18, 2009
Hi Donna,
It's impossible to tell what's chemo and what's natural disease state right now. Basically, I just consider them one and the same. The liver enzyme levels are high enough that we are either dealing with Damp, a TB obstruction, or Blood stasis. Given the Blood deficiency aspects (dreaming, blood counts, coat, etc.), I'm inclined to believe that this is partly where the Blood stasis is coming from. Blood deficiency creates Stasis the way a river that is low in water breaks into stagnant pools and back waters. At the same time, given the pulse, we'd like to decentralize the circulation. Indeed, lymphoma appears to arise from a failure of Yin and Yang to mix properly. Formulas that move Blood out help with this mixing. It is probably through an outer Yin tonification effect that pred helps resolve lymphadenopathy. Chemo is very cold and drying - not what we need and perhaps explaining the failed response of late.
Rolling that altogether, I would try Xue Fu Zhu Yu Tang (with San Leng and E Zhu). It has the bonus of an affinity for the upper burner, where the lymph nodes are most prominent, in addition to its blood moving and tonifying effects. I would use Xiao Chai Hu Tang (Minor Bupleurum) as well, since it facilitates this 'mixing' of Yin and Yang, and thus the movement of Blood outwards from the Liver and into the Yang periphery, where it can 'emolliate' the lymph nodes.
Enough metaphor! Let's give it a try!
Steve
It's impossible to tell what's chemo and what's natural disease state right now. Basically, I just consider them one and the same. The liver enzyme levels are high enough that we are either dealing with Damp, a TB obstruction, or Blood stasis. Given the Blood deficiency aspects (dreaming, blood counts, coat, etc.), I'm inclined to believe that this is partly where the Blood stasis is coming from. Blood deficiency creates Stasis the way a river that is low in water breaks into stagnant pools and back waters. At the same time, given the pulse, we'd like to decentralize the circulation. Indeed, lymphoma appears to arise from a failure of Yin and Yang to mix properly. Formulas that move Blood out help with this mixing. It is probably through an outer Yin tonification effect that pred helps resolve lymphadenopathy. Chemo is very cold and drying - not what we need and perhaps explaining the failed response of late.
Rolling that altogether, I would try Xue Fu Zhu Yu Tang (with San Leng and E Zhu). It has the bonus of an affinity for the upper burner, where the lymph nodes are most prominent, in addition to its blood moving and tonifying effects. I would use Xiao Chai Hu Tang (Minor Bupleurum) as well, since it facilitates this 'mixing' of Yin and Yang, and thus the movement of Blood outwards from the Liver and into the Yang periphery, where it can 'emolliate' the lymph nodes.
Enough metaphor! Let's give it a try!
Steve
by
bannink
August 18, 2009
Donna,
Just thought I would chime in with a few additional thoughts. There are a few studies out looking at the potential for herbs to inhibit the multipledrug resistance P-glycoprotein pump in cancer cells. There are two main reasons lymphoma becomes resistant to cancer. One is that the cancer cells develops a defective apoptotic cascade and cannot commit suicide, therby becoming immortal (can't help you with that problem). The other is that they develop mutation in MDR1/P-glycoprotein which confers multipledrug resistance by essentially pumping the chemotherapy out of the cell. Without getting into a big cell biology lecture, my point is that a metabolite of curcuma has been shown to inhibit the P-gp pump, as well as the mitoxantrone resistance protein, so E Zhu may be particularly helpful in your case. Additionally, Schisandra (Wu Wei Zi), in addition to being hepatoprotective, has also shown an ability to inhibit P-gp. So you might also consider the addition of a formula containing Wu Wei Zi or Schisandra compound and another idea. Especially since this patient is showing signs of multipledrug resistance. Gan Cao is in both Xue Fu Zhu Yu Tang and Xiao Chai Hu Tang and is also good for drug resistance. These are the articles in case you are interested.
Erin
1: Planta Med. 2007 Mar;73(3):212-20. Epub 2007 Feb 22. Links
Schisandrol A from Schisandra chinensis reverses P-glycoprotein-mediated multidrug resistance by affecting Pgp-substrate complexes.
Fong WF, Wan CK, Zhu GY, Chattopadhyay A, Dey S, Zhao Z, Shen XL.
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, P. R. China. wffong@hkbu.edu.hk
Recent studies have shown that dibenzocyclooctadiene lignans may reverse P-glycoprotein-mediated multidrug resistance (Pgp-MDR) in cancer cells; however, the mechanism of action remains unknown. Through screening of herbs, we found that schisandrol A (SCH) isolated from Fructus Schisandrae (the dried fruit of Schisandra chinensis (Turcz.) Baill.) sensitized Pgp-MDR HepG2-DR cells by interfering with the function of Pgp-substrate complexes. In Pgp-MDR cells, SCH enhanced the cytotoxicity of cancer drugs that are Pgp substrates and restored vinblastine-induced G2/M arrest without lowering Pgp expression. SCH increased cellular retention of Pgp substrates such as rhodamine 123. In Pgp-overexpressing membrane preparations, SCH stimulated basal Pgp-ATPase thus showing some substrate-like function. However, SCH was not a competitive inhibitor for verapamil or progesterone and decreased their Km. In the presence of substrates, SCH decreased the reactivity between Pgp and the monoclonal antibody UIC-2 which is normally increased with active substrate-Pgp complexes. The labeling of active Pgp transport sites by [125I]-iodoarylazidoprazosin was partially blocked by SCH. SCH did not affect the activity of the mutant Pgp F983A suggesting that SCH acted differently than the thioxanthene type of Pgp allosteric inhibitors. Our results suggest that SCH acts by affecting the normal formation and functioning of the Pgp-substrate complexes.
1: Mol Cell Biochem. 2007 Feb;296(1-2):85-95. Epub 2006 Sep 8. Links
Modulation of function of three ABC drug transporters, P-glycoprotein (ABCB1), mitoxantrone resistance protein (ABCG2) and multidrug resistance protein 1 (ABCC1) by tetrahydrocurcumin, a major metabolite of curcumin.
Limtrakul P, Chearwae W, Shukla S, Phisalphong C, Ambudkar SV.
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. plimtrak@mail.med.cmu.ac.th
Many studies have been performed with the aim of developing effective resistance modulators to overcome the multidrug resistance (MDR) of human cancers. Potent MDR modulators are being investigated in clinical trials. Many current studies are focused on dietary herbs due to the fact that these have been used for centuries without producing any harmful side effects. In this study, the effect of tetrahydrocurcumin (THC) on three ABC drug transporter proteins, P-glycoprotein (P-gp or ABCB1), mitoxantrone resistance protein (MXR or ABCG2) and multidrug resistance protein 1 (MRP1 or ABCC1) was investigated, to assess whether an ultimate metabolite form of curcuminoids (THC) is able to modulate MDR in cancer cells. Two different types of cell lines were used for P-gp study, human cervical carcinoma KB-3-1 (wild type) and KB-V-1 and human breast cancer MCF-7 (wild type) and MCF-7 MDR, whereas, pcDNA3.1 and pcDNA3.1-MRP1 transfected HEK 293 and MXR overexpressing MCF7AdrVp3000 or MCF7FL1000 and its parental MCF-7 were used for MRP1 and MXR study, respectively. We report here for the first time that THC is able to inhibit the function of P-gp, MXR and MRP1. The results of flow cytometry assay indicated that THC is able to inhibit the function of P-gp and thereby significantly increase the accumulation of rhodamine and calcein AM in KB-V-1 cells. The result was confirmed by the effect of THC on [(3)H]-vinblastine accumulation and efflux in MCF-7 and MCF-7MDR. THC significantly increased the accumulation and inhibited the efflux of [(3)H]-vinblastine in MCF-7 MDR in a concentration-dependent manner. This effect was not found in wild type MCF-7 cell line. The interaction of THC with the P-gp molecule was clearly indicated by ATPase assay and photoaffinity labeling of P-gp with transport substrate. THC stimulated P-gp ATPase activity and inhibited the incorporation of [(125)I]-iodoarylazidoprazosin (IAAP) into P-gp in a concentration-dependent manner. The binding of [(125)I]-IAAP to MXR was also inhibited by THC suggesting that THC interacted with drug binding site of the transporter. THC dose dependently inhibited the efflux of mitoxantrone and pheophorbide A from MXR expressing cells (MCF7AdrVp3000 and MCF7FL1000). Similarly with MRP1, the efflux of a fluorescent substrate calcein AM was inhibited effectively by THC thereby the accumulation of calcein was increased in MRP1-HEK 293 and not its parental pcDNA3.1-HEK 293 cells. The MDR reversing properties of THC on P-gp, MRP1, and MXR were determined by MTT assay. THC significantly increased the sensitivity of vinblastine, mitoxantrone and etoposide in drug resistance KB-V-1, MCF7AdrVp3000 and MRP1-HEK 293 cells, respectively. This effect was not found in respective drug sensitive parental cell lines. Taken together, this study clearly showed that THC inhibits the efflux function of P-gp, MXR and MRP1 and it is able to extend the MDR reversing activity of curcuminoids in vivo.
1: Cancer Chemother Pharmacol. 2002 Apr;49(4):261-6. Epub 2002 Feb 5.
Effects of four Chinese herbal extracts on drug-sensitive and multidrug-resistant small-cell lung carcinoma cells.
Sadava D, Ahn J, Zhan M, Pang ML, Ding J, Kane SE.
Division of Molecular Medicine, City of Hope Medical Center, 1500 E. Duarte Rd., Duarte, CA 91010, USA. dsadava@jsd.claremont.edu
PURPOSE: We examined the pharmacology, cell biology and molecular biology of small-cell lung carcinoma cells treated with four extracts of Chinese herbal medicines. Many cancer patients take these medicines, but their effects at the cellular level are largely unknown. We were especially interested in the effects on drug-resistant cells, as resistance is a significant clinical problem in lung cancer. METHODS: Drug-sensitive (H69), multidrug-resistant (H69VP) and normal lung epithelial cells (BEAS-2) were exposed to extracts from two plants used in Chinese herbal medicine for lung cancer: Glycorrhiza glabra (GLYC) and Olenandria diffusa (OLEN), and to extracts of two commercially available combinations of Chinese herbal medicines, SPES (15 herbs) and PC-SPES (8 herbs). Cytotoxicity was measured in terms of cell growth inhibition (IC(50)). The kinetics of DNA fragmentation after exposure to the herbal extracts was measured by BudR labeling followed by ELISA. Apoptosis was measured by the TUNEL assay followed by flow cytometry. Expression of apoptosis- and cell cycle-related genes was measured by reverse transcription of mRNA followed by filter hybridization to arrays of probes and detection by chemiluminescence. RESULTS: In each case, the four herbal extracts were equally cytotoxic to H69 and H69VP and less cytotoxic to BEAS-2. All four extracts induced DNA fragmentation in the lung carcinoma cells. The kinetics showed DNA fragments released to the medium (an indication of necrosis) in GLYC-exposed cultures, but inside the cells (an indication of apoptosis) in OLEN-, SPES- and PC-SPES-exposed cultures. TUNEL analysis confirmed that exposure to the latter three extracts, but not to GLYC, led to apoptosis. Compared to untreated and GLYC-treated cells, H69 and H69VP cells treated with OLEN, SPES and PC-SPES showed elevated expression of a number of genes involved in the apoptotic cascade, similar to cells treated with etoposide and vincristine. CONCLUSION: The Chinese herbal medicine extracts OLEN, SPES and PC-SPES are cytotoxic to both drug-resistant and drug-sensitive lung cancer cells, show some tumor cell specificity compared to their effect on normal cells, and are proapoptotic as measured by DNA breaks and gene expression. The reaction of the tumor cells to these extracts was similar to their reaction to conventional chemotherapeutic drugs
Just thought I would chime in with a few additional thoughts. There are a few studies out looking at the potential for herbs to inhibit the multipledrug resistance P-glycoprotein pump in cancer cells. There are two main reasons lymphoma becomes resistant to cancer. One is that the cancer cells develops a defective apoptotic cascade and cannot commit suicide, therby becoming immortal (can't help you with that problem). The other is that they develop mutation in MDR1/P-glycoprotein which confers multipledrug resistance by essentially pumping the chemotherapy out of the cell. Without getting into a big cell biology lecture, my point is that a metabolite of curcuma has been shown to inhibit the P-gp pump, as well as the mitoxantrone resistance protein, so E Zhu may be particularly helpful in your case. Additionally, Schisandra (Wu Wei Zi), in addition to being hepatoprotective, has also shown an ability to inhibit P-gp. So you might also consider the addition of a formula containing Wu Wei Zi or Schisandra compound and another idea. Especially since this patient is showing signs of multipledrug resistance. Gan Cao is in both Xue Fu Zhu Yu Tang and Xiao Chai Hu Tang and is also good for drug resistance. These are the articles in case you are interested.
Erin
1: Planta Med. 2007 Mar;73(3):212-20. Epub 2007 Feb 22. Links
Schisandrol A from Schisandra chinensis reverses P-glycoprotein-mediated multidrug resistance by affecting Pgp-substrate complexes.
Fong WF, Wan CK, Zhu GY, Chattopadhyay A, Dey S, Zhao Z, Shen XL.
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong SAR, P. R. China. wffong@hkbu.edu.hk
Recent studies have shown that dibenzocyclooctadiene lignans may reverse P-glycoprotein-mediated multidrug resistance (Pgp-MDR) in cancer cells; however, the mechanism of action remains unknown. Through screening of herbs, we found that schisandrol A (SCH) isolated from Fructus Schisandrae (the dried fruit of Schisandra chinensis (Turcz.) Baill.) sensitized Pgp-MDR HepG2-DR cells by interfering with the function of Pgp-substrate complexes. In Pgp-MDR cells, SCH enhanced the cytotoxicity of cancer drugs that are Pgp substrates and restored vinblastine-induced G2/M arrest without lowering Pgp expression. SCH increased cellular retention of Pgp substrates such as rhodamine 123. In Pgp-overexpressing membrane preparations, SCH stimulated basal Pgp-ATPase thus showing some substrate-like function. However, SCH was not a competitive inhibitor for verapamil or progesterone and decreased their Km. In the presence of substrates, SCH decreased the reactivity between Pgp and the monoclonal antibody UIC-2 which is normally increased with active substrate-Pgp complexes. The labeling of active Pgp transport sites by [125I]-iodoarylazidoprazosin was partially blocked by SCH. SCH did not affect the activity of the mutant Pgp F983A suggesting that SCH acted differently than the thioxanthene type of Pgp allosteric inhibitors. Our results suggest that SCH acts by affecting the normal formation and functioning of the Pgp-substrate complexes.
1: Mol Cell Biochem. 2007 Feb;296(1-2):85-95. Epub 2006 Sep 8. Links
Modulation of function of three ABC drug transporters, P-glycoprotein (ABCB1), mitoxantrone resistance protein (ABCG2) and multidrug resistance protein 1 (ABCC1) by tetrahydrocurcumin, a major metabolite of curcumin.
Limtrakul P, Chearwae W, Shukla S, Phisalphong C, Ambudkar SV.
Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. plimtrak@mail.med.cmu.ac.th
Many studies have been performed with the aim of developing effective resistance modulators to overcome the multidrug resistance (MDR) of human cancers. Potent MDR modulators are being investigated in clinical trials. Many current studies are focused on dietary herbs due to the fact that these have been used for centuries without producing any harmful side effects. In this study, the effect of tetrahydrocurcumin (THC) on three ABC drug transporter proteins, P-glycoprotein (P-gp or ABCB1), mitoxantrone resistance protein (MXR or ABCG2) and multidrug resistance protein 1 (MRP1 or ABCC1) was investigated, to assess whether an ultimate metabolite form of curcuminoids (THC) is able to modulate MDR in cancer cells. Two different types of cell lines were used for P-gp study, human cervical carcinoma KB-3-1 (wild type) and KB-V-1 and human breast cancer MCF-7 (wild type) and MCF-7 MDR, whereas, pcDNA3.1 and pcDNA3.1-MRP1 transfected HEK 293 and MXR overexpressing MCF7AdrVp3000 or MCF7FL1000 and its parental MCF-7 were used for MRP1 and MXR study, respectively. We report here for the first time that THC is able to inhibit the function of P-gp, MXR and MRP1. The results of flow cytometry assay indicated that THC is able to inhibit the function of P-gp and thereby significantly increase the accumulation of rhodamine and calcein AM in KB-V-1 cells. The result was confirmed by the effect of THC on [(3)H]-vinblastine accumulation and efflux in MCF-7 and MCF-7MDR. THC significantly increased the accumulation and inhibited the efflux of [(3)H]-vinblastine in MCF-7 MDR in a concentration-dependent manner. This effect was not found in wild type MCF-7 cell line. The interaction of THC with the P-gp molecule was clearly indicated by ATPase assay and photoaffinity labeling of P-gp with transport substrate. THC stimulated P-gp ATPase activity and inhibited the incorporation of [(125)I]-iodoarylazidoprazosin (IAAP) into P-gp in a concentration-dependent manner. The binding of [(125)I]-IAAP to MXR was also inhibited by THC suggesting that THC interacted with drug binding site of the transporter. THC dose dependently inhibited the efflux of mitoxantrone and pheophorbide A from MXR expressing cells (MCF7AdrVp3000 and MCF7FL1000). Similarly with MRP1, the efflux of a fluorescent substrate calcein AM was inhibited effectively by THC thereby the accumulation of calcein was increased in MRP1-HEK 293 and not its parental pcDNA3.1-HEK 293 cells. The MDR reversing properties of THC on P-gp, MRP1, and MXR were determined by MTT assay. THC significantly increased the sensitivity of vinblastine, mitoxantrone and etoposide in drug resistance KB-V-1, MCF7AdrVp3000 and MRP1-HEK 293 cells, respectively. This effect was not found in respective drug sensitive parental cell lines. Taken together, this study clearly showed that THC inhibits the efflux function of P-gp, MXR and MRP1 and it is able to extend the MDR reversing activity of curcuminoids in vivo.
1: Cancer Chemother Pharmacol. 2002 Apr;49(4):261-6. Epub 2002 Feb 5.
Effects of four Chinese herbal extracts on drug-sensitive and multidrug-resistant small-cell lung carcinoma cells.
Sadava D, Ahn J, Zhan M, Pang ML, Ding J, Kane SE.
Division of Molecular Medicine, City of Hope Medical Center, 1500 E. Duarte Rd., Duarte, CA 91010, USA. dsadava@jsd.claremont.edu
PURPOSE: We examined the pharmacology, cell biology and molecular biology of small-cell lung carcinoma cells treated with four extracts of Chinese herbal medicines. Many cancer patients take these medicines, but their effects at the cellular level are largely unknown. We were especially interested in the effects on drug-resistant cells, as resistance is a significant clinical problem in lung cancer. METHODS: Drug-sensitive (H69), multidrug-resistant (H69VP) and normal lung epithelial cells (BEAS-2) were exposed to extracts from two plants used in Chinese herbal medicine for lung cancer: Glycorrhiza glabra (GLYC) and Olenandria diffusa (OLEN), and to extracts of two commercially available combinations of Chinese herbal medicines, SPES (15 herbs) and PC-SPES (8 herbs). Cytotoxicity was measured in terms of cell growth inhibition (IC(50)). The kinetics of DNA fragmentation after exposure to the herbal extracts was measured by BudR labeling followed by ELISA. Apoptosis was measured by the TUNEL assay followed by flow cytometry. Expression of apoptosis- and cell cycle-related genes was measured by reverse transcription of mRNA followed by filter hybridization to arrays of probes and detection by chemiluminescence. RESULTS: In each case, the four herbal extracts were equally cytotoxic to H69 and H69VP and less cytotoxic to BEAS-2. All four extracts induced DNA fragmentation in the lung carcinoma cells. The kinetics showed DNA fragments released to the medium (an indication of necrosis) in GLYC-exposed cultures, but inside the cells (an indication of apoptosis) in OLEN-, SPES- and PC-SPES-exposed cultures. TUNEL analysis confirmed that exposure to the latter three extracts, but not to GLYC, led to apoptosis. Compared to untreated and GLYC-treated cells, H69 and H69VP cells treated with OLEN, SPES and PC-SPES showed elevated expression of a number of genes involved in the apoptotic cascade, similar to cells treated with etoposide and vincristine. CONCLUSION: The Chinese herbal medicine extracts OLEN, SPES and PC-SPES are cytotoxic to both drug-resistant and drug-sensitive lung cancer cells, show some tumor cell specificity compared to their effect on normal cells, and are proapoptotic as measured by DNA breaks and gene expression. The reaction of the tumor cells to these extracts was similar to their reaction to conventional chemotherapeutic drugs
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