PHY906 is a standardized four-herb traditional Chinese formulation that has been used for over 17... more PHY906 is a standardized four-herb traditional Chinese formulation that has been used for over 1700 years in the treatment of gastrointestinal ailments and is currently in anticancer clinical trials in the US as an adjuvant to chemotherapy. Preliminary clinical results indicated PHY906 could decrease G.I. toxicity triggered by irinotecan for treating colon cancer. In a murine colon-38 allograft model, PHY906 (500 mg bid days 0-3) alone, does not significantly inhibit tumor growth. However, the combination of PHY906 and irinotecan (360mg/kg, day 1) had higher anti-tumor activity in comparison to irinotecan alone. Additionally, PHY906 decreased weight loss caused by irinotecan. The impact of PHY906 on the intestinal toxicity caused by irinotecan at day 2 and day 4 were studied. Adding PHY906 to irinotecan treatment, a) reduced irinotecan induced degenerative changes throughout different regions of the intestine on day 4 but not on day 2, b) reduced irinotecan induced DNA damage and apoptosis of intestinal cells on day 4, c) promoted the re-growth of crypt cells which could be partially attributed to the wnt3a-potentiation activity of the aglycone component(s) of PHY906 on day 4, d) inhibited TNF-\#945; induced NF-kB activity, e) decreased the infiltration of neutrophils in intestinal crypt areas and decreased pro-inflammatory cytokine levels. In summary, our studies suggest that PHY906 reduces intestinal damage caused by irinotecan through the inhibition of inflammation and enhancement of intestinal repair by promoting intestinal progenitor cell proliferation. This work is supported by a supplement grant: CA-63477 from NCI, USA Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4584.
15152 Traditional botanical formulations in combination with conventional antitumor chemotherapeu... more 15152 Traditional botanical formulations in combination with conventional antitumor chemotherapeutics may prove a powerful approach in reducing toxicity and improving clinical outcomes. In vivo studies show that PHY906, a traditional Chinese formulation, can reduce chemo-induced gastrointestinal toxicity while enhancing the therapeutic efficacy of a broad-spectrum of common anticancer agents in various cancer models, including capecitabine, CPT-11, thalidomide, adriamycin, and sorafenib in liver cancer; gemcitabine, capecitabine, oxaliplatin, gem/ox in pancreatic cancer; and CPT-11, 5-FU, sorafenib, VP-16, L-OddC, CPT-11/5-FU/LV, and oxaliplatin/5-FU/LV in colorectal cancer. Co- administration of PHY906 with a host of chemotherapeutic agents appears to neither alter the pharmacokinetic profiles of the chemotherapeutic agents nor their respective metabolites. PHY906 is currently being studied in a phase I/II, multicenter, open-label, dose-modification, safety and efficacy study in combination with capecitabine in patients with non-resectable HCC in the U.S. and Taiwan. Phase I patients (n=18) were enrolled at COH, Yale, VA and Stanford beginning November 2003. The primary objective of phase I was the determination of a safe dose regimen by varying the dose levels of PHY906 and/or capecitabine. Three dose levels of PHY906 + capecitabine were evaluated: PHY906 1000 mg BID + Capecitabine 1000 mg/m2 BID; PHY906 600 mg BID + Capecitabine 750 mg/m2 BID; and PHY906 800 mg BID + Capecitabine 750 mg/m2 BID. The final dosing level was chosen for the phase II portion of the study. Preliminary results suggest that the quality of life of patients on PHY906 + capecitabine was improved when compared to historical controls studying capecitabine alone. There is also no evidence of drug-induced toxicity caused by PHY906; nor does PHY906 reduce capecitabine antitumor activity. For patients receiving capecitabine at 750 mg/m2 BID and PHY906 at either 600 mg BID (N=4) or 800 mg BID (N=24), 10.7% (N=3) achieved minor response (MR), 50% (N=14) had stable disease (SD) and 39.3% (N=11) had progressive disease (PD). These findings support the further investigation of PHY906 as an adjuvant therapy of capecitabine in a larger HCC population. No significant financial relationships to disclose.
Panax notoginseng (Burk.) F.H.Chen is a well known Chinese medicinal plant. Its radix is used in ... more Panax notoginseng (Burk.) F.H.Chen is a well known Chinese medicinal plant. Its radix is used in the history while its flower is recently used for health care. In this study we compared chemical ingredients and bioactivities in cell culture for radix and flower of Panax notoginseng (Burk.) F.H.Chen. The liquid chromatography-mass spectrometry system was applied to determine the contents of saponins in flower and radix of Panax notoginseng (Burk.) F.H.Chen. Transcription specific luciferase reporter assay and qPCR method for selected RNA were carried out to assess the impacts of flower and radix extract on the transcription signal pathways. The results of chemical analysis showed that the contents of saponins in flower and radix are very different: the contents of Rg1, Rb1, Re, R1, Rg3-20R, Rh1 and Rf in radix are abundant; in contrast, the contents of Rb3, Fc, Ft1, Rb2 and Rh2-20s in flowers are plentiful. There are substantial variations of those saponin contents from one batch vs another. Based on relative content of saponins, the chemosynthesis pathway of ingredients in radix and flower are proposed: for radix, both PPT (Protopanaxatriol) and PPD (Protopanaxadiol) type triterpenoids are involved, the main pathway is PPT→Rb1 →Rg1→R1 or PPD→Rh2 20s→Rg3(20s) →Rd →Rb1;for flowers, only PPD is main passage with PPD →Rh2 (20s)→Rg3(20s) →Rd→Rb2 →Fc. The results of signal transcription assays demonstrated that herb water extract of radix and flower had no significant influences on most of transcription activities. However, total saponins of radix and flower which have highly content of saponins were able to inhibit the inflammatory related transcriptional activities and their related mRNA expression of IFNα, TNFα, il-6 and TGFβ as well as induce anti-oxygen NrF2 activities. In summary, although chemical ingredients and chemosynthesis pathway of flower and radix for Panax notoginseng (Burk.) F.H.Chen were different, these differences might not result in their differences of pharmacological activities.
Background: Targeted therapy using immune checkpoint inhibitors (ICIs) is a major breakthrough in... more Background: Targeted therapy using immune checkpoint inhibitors (ICIs) is a major breakthrough in cancer treatment in the last decade. ICIs like PD1 or PD-L1 antibodies have been shown to be quite effective in cancer like melanoma. However, in most other tumor types including breast cancer, the situation is not as optimistic. Only a small percentage of those patients respond to ICIs therapy. This highlights the importance of identifying biomarkers to predict which patients may benefit from such treatment. Tumor Mutation Burden (TMB) has been shown to be a sensitive marker for ICI treatment. This study is to investigate whether TBM could be used as a biomarker for breast cancer treatment. Methods: We reviewed next generation sequencing studies of breast cancer. Two such studies with raw data provided were included in our analysis. One study entitled METABRIC performed targeted sequencing of 173 cancer-related genes in around 2500 primary breast cancer tissues. The other study was from TCGA breast cancer project, which performed Whole Exome Sequencing (WES) of around 1000 primary breast cancer samples. Mutation data were downloaded from public data deposit. The number of mutations per sample was calculated. TBM was calculated by divide the coverage in million base pair from that of the total mutation counts. Results: In METABRIC study, 17272 mutations were identified in 2369 samples, with a median of 7 mutations per sample (95% CI: 6 ˜ 7). The median TMB of METABRIC dataset was 5.8 SNVs/Mb (95% CI: 5 ˜ 5.8). Totally 30 out 2369 (1.3%) samples had a TMB equal or large than 20 SNVs/Mb. In another cohort from TCGA breast cancer study using WES technology, 90172 mutations were identified in 977 samples, with a median of 44 mutations per sample (95% CI: 39 ˜ 50). The median TMB was 1 SNVs/Mb (95% CI: 0.9 ˜ 1.1). Totally 13 out 977 (1.3%) samples had a TMB equal or large than 20 SNVs/Mb. Conclusions: Breast cancer shows middle to low mutation burden compared to other cancer types. Around 1.3% of breast cancer has quite high TMB of at least 20 SNVs/Mb, which may be qualified for immune checkpoint inhibitors therapy. Our study indicates that TMB may be incorporated as a standard test for late stage breast cancer patients in the clinical practice. Keywords: Breast cancer, Tumor Mutation Burden, Whole exome sequencing, Targeted sequencing, Immune checkpoint Citation Format: Wang J, Chen W, Jiang Z, Lin X, Qin T, Yang X, Liu T, Hu H, Li Z, Xie D, Yao H, Song E. A small amount of primary breast cancer shows high tumor mutation burden that may benefit from immune checkpoint inhibitor therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-04-11.
YIV-906 (PHY906) is inspired by a traditional 1800-year Chinese herbal formulation, “Huang Qin Ta... more YIV-906 (PHY906) is inspired by a traditional 1800-year Chinese herbal formulation, “Huang Qin Tang”, which is commonly used for treating diarrhea. Following chemotherapy and radiation, preclinical and clinical results suggest that YIV-906 has the potential to improve the patient’s quality of life and prolonging survival. Consistent preparations of PHY906 could be manufactured apart 15 years. The effects of YIV-906 were studied on the anti-tumor activity of anti-PD1 using BDF1 mice bearing Hepa 1-6 tumors. Results indicated that anti-PD1 alone had moderate effects on tumor growth however YIV-906 plus anti-PD1 eradicated all tumors in all tumor bearing mice. Further re-implantation of Hepa 1-6 cells did not grow in the “cured” mice, but implanted CMT167 (non-small lung carcinoma) cells or Pan02 (Pancreatic Ductal Adenocarcinoma) cells did grow; suggesting that YIV-906 plus anti-PD1 created a tumor-specific vaccine-like effect. The combination treatment exhibited a highly inflamed tumor microenvironment with more M1-like macrophage expression over M2. In culture YIV-906 could potentiate the action of IFNg (interferon gamma) to polarize bone marrow-derived macrophages (BMDM) into M1 macrophages while inhibiting IL4 action for M2 macrophage polarization. YIV-906 potentiated IFNg action through: 1) stimulating IFNg secretion, 2) phosphorylation of JAK1/2 and STAT1 and 3) increasing IRF1 protein expression. Scutellaria baicalensis Georgi (S) and its flavonoids of YIV-906 were responsible for potentiate the IFNg to polarize macrophage into M1. In conclusion, YIV-906 enhanced the anti-tumor activity of anti-PD1 by enhancing inflammation in the tumor microenvironment and enriching M1-like macrophages. This suggests the potential use of combination YIV-906 and anti-PD1 in cancer treatment. This work was supported by grant (1PO1CA154295-01A1) from National Cancer Institute (NCI), NIH, USA. Dr. Yung-Chi Cheng is a fellow of National Foundation for Cancer Research (NFCR), USA. Citation Format: Wing Lam, Xiaochen Yang, Zaoli Jiang, Xue han, Fulan Guan, Rong Hu, Chang-Hua Xu, Wei Cai, William Cheng, Shwu-Huey Liu, Yuping Cai, Nicholas Rattray, Caroline Johnson, Lieping Chen, Yung-chi Cheng. YIV-906 (PHY906) enhanced the anti-tumor activity of immune checkpoint blockade therapy (Anti-PD1) against liver cancer by changing the tumor micro-environment associated with M1 macrophages infiltration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2252.
Two compounds having a camptothecin (CPT) analog conjugated to the 4-amino-4Ј-Odemethylepipodoph... more Two compounds having a camptothecin (CPT) analog conjugated to the 4-amino-4Ј-Odemethylepipodophyllotoxin analog were evaluated for their biochemical and biological activities. W1 [camptothecin-(para)-4-amino-4Ј-O-demethylepipodophyllotoxin] had no activity against topoisomerase II (TOP II), but inhibited topoisomerase I (TOP I) with an IC 50 value 2-fold higher than CPT. W2 [camptothecin-(ortho)-4-amino-4Ј-O-demethylepipodophyllotoxin] had inhibitory activity against TOP I and TOP II with IC 50 values 1.5-fold higher than either CPT or etoposide (VP-16). Both conjugates had similar cytotoxicity against the KB cell line, although the protein-linked DNA breaks (PLDBs) generated by W2 in KB cells were about 4-fold more than those of W1. No cross-resistance with the two conjugates was seen in a VP-16-resistant KB subline, which showed down-regulation of TOP II and overexpression of the multiple drug resistance-associated protein, or in a vincristine-resistant KB subline with overexpression of gp-170/mdr-1. The CPT-resistant KB variant (KB CPT 100), which has a reduction in TOP I content and another mechanism that occurs post-PLDB formation, was partially resistant to both compounds. W1 was not affected by this post-PLDB resistance mechanism. Cell cycle analysis demonstrated that W1 and W2 had similar cell cycle effects on KB and KB CPT 100 cells, which accumulated in S-phase upon drug treatment. These results suggested that W1 and W2 exerted their cytotoxicity through TOP I. In CPT-resistant cells, however, an unidentified target also may be involved in the cytotoxic action of W1, and TOP II may still be a target for W2. In vivo, W1 was more effective against the growth of human prostate cancer cells in nude mice than VP-16, CPT, or W2. Given its antitumor activity and unique biochemical mechanism of action, W1 warrants exploration as an antitumor compound.
Lebensmittel-Wissenschaft & Technologie, Mar 1, 2019
The aim was to establish a rapid and quantitative detection method of formaldehyde in squid based... more The aim was to establish a rapid and quantitative detection method of formaldehyde in squid based on electronic nose for screening massive samples. Identification of volatile compounds in squid with different formaldehyde content by electronic nose were mainly depended on eight sensors. Besides, the diversities of volatile constituents in squid with increasing contents of aldehydes and aromatic compounds were validated by GC-MS results. Moreover, to build a qualitative discrimination model for estimating whether formaldehyde in squid over standard limit or not, DFA and SIMCA based on PCA were used to analyze electronic nose data for semi-quantitative determination of formaldehyde content in squid. Finally, a rapid quantitative prediction model based on electronic nose and PLS was established (R 2 =0.9266).To verify the accuracy of quantitative model, t-test was employed and no significant difference between predicted values and true values was found. This approach showed well potentiality to provide a rapid, nondestructive and quantitative method for detecting formaldehyde residue in food.
YIV-906 (PHY906) is a standardized botanical cancer drug candidate developed with a systems biolo... more YIV-906 (PHY906) is a standardized botanical cancer drug candidate developed with a systems biology approach-inspired by a traditional Chinese herbal formulation, historically used to treat gastrointestinal symptoms including diarrhea, nausea and vomiting. In combination with chemotherapy and/or radiation therapy, preclinical and clinical results suggest that YIV-906 has the potential to prolong survival and improve quality of life for cancer patients. Here, we demonstrated that YIV-906 plus anti-PD1 could eradicate all Hepa 1-6 tumors in all tumor bearing mice. YIV-906 was found to have multiple mechanisms of action to enhance adaptive and innate immunity. In combination, YIV-906 reduced PD1 or counteracted PDL1 induction caused by anti-PD1 which led to higher T-cell activation gene expression of the tumor. In addition, YIV-906 could reduce immune tolerance by modulating IDO activity and reducing monocytic MDSC of the tumor. The combination of anti-PD1 and YIV-906 generated acute in ammation in the tumor microenvironment with more M1-like macrophages. YIV-906 could potentiate the action of IFNg to increase M1-like macrophage polarization while inhibiting IL4 action to decrease M2 macrophage polarization. Flavonoids from YIV-906 were responsible for modulating IDO activity and potentiating IFNg action in M1-like macrophage polarization. In conclusion, YIV-906 could act as an immunomodulator and enhance the innate and adaptive immune response and potentiate anti-tumor activity for immunotherapies to treat cancer.
2145 PHY906, a traditional Chinese botanical formulation, was first described 1800 years ago for ... more 2145 PHY906, a traditional Chinese botanical formulation, was first described 1800 years ago for common gastrointestinal distress. Currently, PHY906 is being developed for FDA approval as a botanical prescription medicine offering a new approach to cancer supportive care. The preclinical data indicates that PHY906 can reduce chemo-induced gastrointestinal toxicity while simultaneously enhancing the therapeutic efficacy of a broad-spectrum of common anticancer agents, including CPT-11, 5-FU, capecitabine, oxaliplatin, VP-16, taxol, and gemcitabine in a variety of tumor-implanted in vivo animal models. The mechanism of PHY906 antitumor activity is multifarious, including inhibitory activities of NF-κB, matrix metalloproteases (MMPs), multi-drug resistant protein (MDR), and CYP450 and modulation of numerous cytokines. Possible mechanisms of action for the reduction of gastrointestinal toxicity are the inhibition of Tachykinin NK-1 and Opiate δ receptors and modulation of inflammatory cytokines. A phase I/II, multicenter, open-label, dose-escalation, safety and efficacy study of PHY906 plus capecitabine in patients with unresectable hepatocellular carcinoma is presently underway. The main objective of phase I is to define the safety, tolerability, and effective dose of PHY906 when co-administered with capecitabine. Three doses have been studied. Cohort I: PHY906 (1000mg, bid, D1-4 and 8-11) plus capecitabine (1000 mg/m2,bid, D1-14); cohort II: PHY906 (600mg, bid, D1-4 and 8-11) plus capecitabine (750 mg/m2, bid, D1-14); and cohort III: PHY906 (800mg, bid, D1-4 and 8-11) plus capecitabine (750 mg/m2, bid, D1-14). The cohort I dose regimen has resulted in unacceptable dose-limiting toxicities while the dosing in cohorts II and III were both well tolerated. Stable disease after two cycles of study-drug treatment for cohorts II (N=4) and III (N=6) are 75% and 67%, respectively. The median time to disease progression (TTP) is 26.5 weeks and the median survival time is greater than 44.5 weeks for Cohort II. The majority of the patients in Cohort III remain on study. The primary objective for the current phase II is determining the objective antitumor response rate while the secondary objectives are determining TTP, overall survival time, and quality of life (QoL). While clinical trials address efficacy and safety of the drug, chemical and biological analytic methods have been developed to address drug consistency and quality control. Comprehensive molecular resolution chemical fingerprints utilizing a three-dimensional LC/MS profile and a sensitive cellular bioresponse genomic profile to generate a quantitative signature pattern for comparing and confirming batch-to-batch similarity of study drug. These studies offer a modern approach to the study of ancient botanicals that may represent novel regimens for cancer treatment.
557 PHY906 is a traditional Chinese botanical formulation consisting of 4 different herbs, and it... more 557 PHY906 is a traditional Chinese botanical formulation consisting of 4 different herbs, and it has been used for some 1800 years to treat gastrointestinal ailments, some of which are commonly observed side effects in cancer patients undergoing chemotherapy. We have previously reported that PHY906 reduced chemotherapy-induced toxicities including body weight loss and mortality, and that it also enhanced the antitumor efficacy of a broad-spectrum of anticancer agents, such as CPT-11, 5-FU, CPT-11/5-FU/LV, VP-16, and L-OddC in in vivo animal models. PHY906 has been co-administrated with either the oral 5-FU prodrug capecitabine or CPT-11 in human hepatocellular xenografts mouse model, and with gemcitabine in mouse pancreatic cancer model. We have shown that PHY906 significantly enhanced the therapeutic index of chemotherapeutic agents studied in both hepatocellular and pancreatic cancer models. Co-administration of PHY906 with either capecitabine or gemcitabine in animal models did not alter the pharmacokinetic profile of capecitabine, gemcitabine, or their respective metabolites. Our biochemical studies revealed that the PHY906 formulation possesses a wide range of pharmacological activities. The potential mechanism(s) of action of PHY906 include (1) enhancement of oral uptake of pharmacologically active agents with inhibition in intestinal CYP3A4; (2) inhibition of NF-κB activity; (3) inhibition of MMP activity; and (4) destruction of the integrity of sinusoids in hepatoma. These pre-clinical in vivo studies have provided rationale for developing PHY906 in the clinical setting. A phase I/IIA double-blind placebo-controlled, dose escalation study of PHY906 was initiated to evaluate the potential effect of PHY906 in modulating CPT-11-induced diarrhea associated with the bolus, weekly schedule of CPT-11/5-FU/LV in advanced colorectal cancer patients. A second phase I/II open-label dose escalation clinical trial has just been opened to patient accrual to evaluate the role of PHY906 in combination with capecitabine in the treatment of hepatocellular carcinoma.
Background-: Traditional Chinese Medicine (TCM) has been used for thousands of years to treat or ... more Background-: Traditional Chinese Medicine (TCM) has been used for thousands of years to treat or prevent diseases, including cancer. Good manufacturing practices (GMP) and sophisticated product analysis (PhytomicsQC) to ensure consistency are now available allowing the assessment of its utility. Polychemical Medicines, like TCM, include chemicals with distinct tissue-dependent pharmacodynamic properties that result in tissue-specific bioactivity. Determining the mode of action of these mixtures was previously unsatisfactory; however, information rich RNA microarray technologies now allow for thorough mechanistic studies of the effects complex mixtures. PHY906 is a long used four herb TCM formula employed as an adjuvant to relieve the side effects associated with chemotherapy. Animal studies documented a decrease in global toxicity and an increase in therapeutic effectiveness of chemotherapy when combined with PHY906. Methods-: Using a systems biology approach, we studied tumor tissu...
Cette invention porte sur des compositions vegetales utiles pour augmenter l'indice therapeut... more Cette invention porte sur des compositions vegetales utiles pour augmenter l'indice therapeutique de composes chimiotherapeutiques. Cette invention porte egalement sur des procedes utiles pour ameliorer la qualite de vie d'un patient subissant une chimiotherapie. De plus, cette invention ameliore le traitement d'un cancer par l'administration de la composition vegetale PHY906 en combinaison avec un ou plusieurs composes chimiotherapeutiques chez un mammifere subissant une telle chimiotherapie.
2145 PHY906, a traditional Chinese botanical formulation, was first described 1800 years ago for ... more 2145 PHY906, a traditional Chinese botanical formulation, was first described 1800 years ago for common gastrointestinal distress. Currently, PHY906 is being developed for FDA approval as a botanical prescription medicine offering a new approach to cancer supportive care. The preclinical data indicates that PHY906 can reduce chemo-induced gastrointestinal toxicity while simultaneously enhancing the therapeutic efficacy of a broad-spectrum of common anticancer agents, including CPT-11, 5-FU, capecitabine, oxaliplatin, VP-16, taxol, and gemcitabine in a variety of tumor-implanted in vivo animal models. The mechanism of PHY906 antitumor activity is multifarious, including inhibitory activities of NF-κB, matrix metalloproteases (MMPs), multi-drug resistant protein (MDR), and CYP450 and modulation of numerous cytokines. Possible mechanisms of action for the reduction of gastrointestinal toxicity are the inhibition of Tachykinin NK-1 and Opiate δ receptors and modulation of inflammatory c...
e13571 Background: The goal of this phase I study was to determine the maximum tolerated dose (MT... more e13571 Background: The goal of this phase I study was to determine the maximum tolerated dose (MTD) of the oral Chinese herbal medication PHY906 when combined with CPT-11. PHY906 has been used in A...
Panax notoginseng (Burk.) F.H.Chen is a well known Chinese medicinal plant. Its radix is used in ... more Panax notoginseng (Burk.) F.H.Chen is a well known Chinese medicinal plant. Its radix is used in the history while its flower is recently used for health care. In this study we compared chemical ingredients and bioactivities in cell culture for radix and flower of Panax notoginseng (Burk.) F.H.Chen. The liquid chromatography-mass spectrometry system was applied to determine the contents of saponins in flower and radix of Panax notoginseng (Burk.) F.H.Chen. Transcription specific luciferase reporter assay and qPCR method for selected RNA were carried out to assess the impacts of flower and radix extract on the transcription signal pathways. The results of chemical analysis showed that the contents of saponins in flower and radix are very different: the contents of Rg1, Rb1, Re, R1, Rg3-20R, Rh1 and Rf in radix are abundant; in contrast, the contents of Rb3, Fc, Ft1, Rb2 and Rh2-20s in flowers are plentiful. There are substantial variations of those saponin contents from one batch vs ...
YIV-906 (PHY906) is a standardized botanical cancer drug candidate developed with a systems biolo... more YIV-906 (PHY906) is a standardized botanical cancer drug candidate developed with a systems biology approach—inspired by a traditional Chinese herbal formulation, historically used to treat gastrointestinal symptoms including diarrhea, nausea and vomiting. In combination with chemotherapy and/or radiation therapy, preclinical and clinical results suggest that YIV-906 has the potential to prolong survival and improve quality of life for cancer patients. Here, we demonstrated that YIV-906 plus anti-PD1 could eradicate all Hepa 1–6 tumors in all tumor bearing mice. YIV-906 was found to have multiple mechanisms of action to enhance adaptive and innate immunity. In combination, YIV-906 reduced PD1 or counteracted PD-L1 induction caused by anti-PD1 which led to higher T-cell activation gene expression of the tumor. In addition, YIV-906 could reduce immune tolerance by modulating IDO activity and reducing monocytic MDSC of the tumor. The combination of anti-PD1 and YIV-906 generated acute ...
PHY906 is a standardized four-herb traditional Chinese formulation that has been used for over 17... more PHY906 is a standardized four-herb traditional Chinese formulation that has been used for over 1700 years in the treatment of gastrointestinal ailments and is currently in anticancer clinical trials in the US as an adjuvant to chemotherapy. Preliminary clinical results indicated PHY906 could decrease G.I. toxicity triggered by irinotecan for treating colon cancer. In a murine colon-38 allograft model, PHY906 (500 mg bid days 0-3) alone, does not significantly inhibit tumor growth. However, the combination of PHY906 and irinotecan (360mg/kg, day 1) had higher anti-tumor activity in comparison to irinotecan alone. Additionally, PHY906 decreased weight loss caused by irinotecan. The impact of PHY906 on the intestinal toxicity caused by irinotecan at day 2 and day 4 were studied. Adding PHY906 to irinotecan treatment, a) reduced irinotecan induced degenerative changes throughout different regions of the intestine on day 4 but not on day 2, b) reduced irinotecan induced DNA damage and apoptosis of intestinal cells on day 4, c) promoted the re-growth of crypt cells which could be partially attributed to the wnt3a-potentiation activity of the aglycone component(s) of PHY906 on day 4, d) inhibited TNF-\#945; induced NF-kB activity, e) decreased the infiltration of neutrophils in intestinal crypt areas and decreased pro-inflammatory cytokine levels. In summary, our studies suggest that PHY906 reduces intestinal damage caused by irinotecan through the inhibition of inflammation and enhancement of intestinal repair by promoting intestinal progenitor cell proliferation. This work is supported by a supplement grant: CA-63477 from NCI, USA Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 4584.
15152 Traditional botanical formulations in combination with conventional antitumor chemotherapeu... more 15152 Traditional botanical formulations in combination with conventional antitumor chemotherapeutics may prove a powerful approach in reducing toxicity and improving clinical outcomes. In vivo studies show that PHY906, a traditional Chinese formulation, can reduce chemo-induced gastrointestinal toxicity while enhancing the therapeutic efficacy of a broad-spectrum of common anticancer agents in various cancer models, including capecitabine, CPT-11, thalidomide, adriamycin, and sorafenib in liver cancer; gemcitabine, capecitabine, oxaliplatin, gem/ox in pancreatic cancer; and CPT-11, 5-FU, sorafenib, VP-16, L-OddC, CPT-11/5-FU/LV, and oxaliplatin/5-FU/LV in colorectal cancer. Co- administration of PHY906 with a host of chemotherapeutic agents appears to neither alter the pharmacokinetic profiles of the chemotherapeutic agents nor their respective metabolites. PHY906 is currently being studied in a phase I/II, multicenter, open-label, dose-modification, safety and efficacy study in combination with capecitabine in patients with non-resectable HCC in the U.S. and Taiwan. Phase I patients (n=18) were enrolled at COH, Yale, VA and Stanford beginning November 2003. The primary objective of phase I was the determination of a safe dose regimen by varying the dose levels of PHY906 and/or capecitabine. Three dose levels of PHY906 + capecitabine were evaluated: PHY906 1000 mg BID + Capecitabine 1000 mg/m2 BID; PHY906 600 mg BID + Capecitabine 750 mg/m2 BID; and PHY906 800 mg BID + Capecitabine 750 mg/m2 BID. The final dosing level was chosen for the phase II portion of the study. Preliminary results suggest that the quality of life of patients on PHY906 + capecitabine was improved when compared to historical controls studying capecitabine alone. There is also no evidence of drug-induced toxicity caused by PHY906; nor does PHY906 reduce capecitabine antitumor activity. For patients receiving capecitabine at 750 mg/m2 BID and PHY906 at either 600 mg BID (N=4) or 800 mg BID (N=24), 10.7% (N=3) achieved minor response (MR), 50% (N=14) had stable disease (SD) and 39.3% (N=11) had progressive disease (PD). These findings support the further investigation of PHY906 as an adjuvant therapy of capecitabine in a larger HCC population. No significant financial relationships to disclose.
Panax notoginseng (Burk.) F.H.Chen is a well known Chinese medicinal plant. Its radix is used in ... more Panax notoginseng (Burk.) F.H.Chen is a well known Chinese medicinal plant. Its radix is used in the history while its flower is recently used for health care. In this study we compared chemical ingredients and bioactivities in cell culture for radix and flower of Panax notoginseng (Burk.) F.H.Chen. The liquid chromatography-mass spectrometry system was applied to determine the contents of saponins in flower and radix of Panax notoginseng (Burk.) F.H.Chen. Transcription specific luciferase reporter assay and qPCR method for selected RNA were carried out to assess the impacts of flower and radix extract on the transcription signal pathways. The results of chemical analysis showed that the contents of saponins in flower and radix are very different: the contents of Rg1, Rb1, Re, R1, Rg3-20R, Rh1 and Rf in radix are abundant; in contrast, the contents of Rb3, Fc, Ft1, Rb2 and Rh2-20s in flowers are plentiful. There are substantial variations of those saponin contents from one batch vs another. Based on relative content of saponins, the chemosynthesis pathway of ingredients in radix and flower are proposed: for radix, both PPT (Protopanaxatriol) and PPD (Protopanaxadiol) type triterpenoids are involved, the main pathway is PPT→Rb1 →Rg1→R1 or PPD→Rh2 20s→Rg3(20s) →Rd →Rb1;for flowers, only PPD is main passage with PPD →Rh2 (20s)→Rg3(20s) →Rd→Rb2 →Fc. The results of signal transcription assays demonstrated that herb water extract of radix and flower had no significant influences on most of transcription activities. However, total saponins of radix and flower which have highly content of saponins were able to inhibit the inflammatory related transcriptional activities and their related mRNA expression of IFNα, TNFα, il-6 and TGFβ as well as induce anti-oxygen NrF2 activities. In summary, although chemical ingredients and chemosynthesis pathway of flower and radix for Panax notoginseng (Burk.) F.H.Chen were different, these differences might not result in their differences of pharmacological activities.
Background: Targeted therapy using immune checkpoint inhibitors (ICIs) is a major breakthrough in... more Background: Targeted therapy using immune checkpoint inhibitors (ICIs) is a major breakthrough in cancer treatment in the last decade. ICIs like PD1 or PD-L1 antibodies have been shown to be quite effective in cancer like melanoma. However, in most other tumor types including breast cancer, the situation is not as optimistic. Only a small percentage of those patients respond to ICIs therapy. This highlights the importance of identifying biomarkers to predict which patients may benefit from such treatment. Tumor Mutation Burden (TMB) has been shown to be a sensitive marker for ICI treatment. This study is to investigate whether TBM could be used as a biomarker for breast cancer treatment. Methods: We reviewed next generation sequencing studies of breast cancer. Two such studies with raw data provided were included in our analysis. One study entitled METABRIC performed targeted sequencing of 173 cancer-related genes in around 2500 primary breast cancer tissues. The other study was from TCGA breast cancer project, which performed Whole Exome Sequencing (WES) of around 1000 primary breast cancer samples. Mutation data were downloaded from public data deposit. The number of mutations per sample was calculated. TBM was calculated by divide the coverage in million base pair from that of the total mutation counts. Results: In METABRIC study, 17272 mutations were identified in 2369 samples, with a median of 7 mutations per sample (95% CI: 6 ˜ 7). The median TMB of METABRIC dataset was 5.8 SNVs/Mb (95% CI: 5 ˜ 5.8). Totally 30 out 2369 (1.3%) samples had a TMB equal or large than 20 SNVs/Mb. In another cohort from TCGA breast cancer study using WES technology, 90172 mutations were identified in 977 samples, with a median of 44 mutations per sample (95% CI: 39 ˜ 50). The median TMB was 1 SNVs/Mb (95% CI: 0.9 ˜ 1.1). Totally 13 out 977 (1.3%) samples had a TMB equal or large than 20 SNVs/Mb. Conclusions: Breast cancer shows middle to low mutation burden compared to other cancer types. Around 1.3% of breast cancer has quite high TMB of at least 20 SNVs/Mb, which may be qualified for immune checkpoint inhibitors therapy. Our study indicates that TMB may be incorporated as a standard test for late stage breast cancer patients in the clinical practice. Keywords: Breast cancer, Tumor Mutation Burden, Whole exome sequencing, Targeted sequencing, Immune checkpoint Citation Format: Wang J, Chen W, Jiang Z, Lin X, Qin T, Yang X, Liu T, Hu H, Li Z, Xie D, Yao H, Song E. A small amount of primary breast cancer shows high tumor mutation burden that may benefit from immune checkpoint inhibitor therapy [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P4-04-11.
YIV-906 (PHY906) is inspired by a traditional 1800-year Chinese herbal formulation, “Huang Qin Ta... more YIV-906 (PHY906) is inspired by a traditional 1800-year Chinese herbal formulation, “Huang Qin Tang”, which is commonly used for treating diarrhea. Following chemotherapy and radiation, preclinical and clinical results suggest that YIV-906 has the potential to improve the patient’s quality of life and prolonging survival. Consistent preparations of PHY906 could be manufactured apart 15 years. The effects of YIV-906 were studied on the anti-tumor activity of anti-PD1 using BDF1 mice bearing Hepa 1-6 tumors. Results indicated that anti-PD1 alone had moderate effects on tumor growth however YIV-906 plus anti-PD1 eradicated all tumors in all tumor bearing mice. Further re-implantation of Hepa 1-6 cells did not grow in the “cured” mice, but implanted CMT167 (non-small lung carcinoma) cells or Pan02 (Pancreatic Ductal Adenocarcinoma) cells did grow; suggesting that YIV-906 plus anti-PD1 created a tumor-specific vaccine-like effect. The combination treatment exhibited a highly inflamed tumor microenvironment with more M1-like macrophage expression over M2. In culture YIV-906 could potentiate the action of IFNg (interferon gamma) to polarize bone marrow-derived macrophages (BMDM) into M1 macrophages while inhibiting IL4 action for M2 macrophage polarization. YIV-906 potentiated IFNg action through: 1) stimulating IFNg secretion, 2) phosphorylation of JAK1/2 and STAT1 and 3) increasing IRF1 protein expression. Scutellaria baicalensis Georgi (S) and its flavonoids of YIV-906 were responsible for potentiate the IFNg to polarize macrophage into M1. In conclusion, YIV-906 enhanced the anti-tumor activity of anti-PD1 by enhancing inflammation in the tumor microenvironment and enriching M1-like macrophages. This suggests the potential use of combination YIV-906 and anti-PD1 in cancer treatment. This work was supported by grant (1PO1CA154295-01A1) from National Cancer Institute (NCI), NIH, USA. Dr. Yung-Chi Cheng is a fellow of National Foundation for Cancer Research (NFCR), USA. Citation Format: Wing Lam, Xiaochen Yang, Zaoli Jiang, Xue han, Fulan Guan, Rong Hu, Chang-Hua Xu, Wei Cai, William Cheng, Shwu-Huey Liu, Yuping Cai, Nicholas Rattray, Caroline Johnson, Lieping Chen, Yung-chi Cheng. YIV-906 (PHY906) enhanced the anti-tumor activity of immune checkpoint blockade therapy (Anti-PD1) against liver cancer by changing the tumor micro-environment associated with M1 macrophages infiltration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2252.
Two compounds having a camptothecin (CPT) analog conjugated to the 4-amino-4Ј-Odemethylepipodoph... more Two compounds having a camptothecin (CPT) analog conjugated to the 4-amino-4Ј-Odemethylepipodophyllotoxin analog were evaluated for their biochemical and biological activities. W1 [camptothecin-(para)-4-amino-4Ј-O-demethylepipodophyllotoxin] had no activity against topoisomerase II (TOP II), but inhibited topoisomerase I (TOP I) with an IC 50 value 2-fold higher than CPT. W2 [camptothecin-(ortho)-4-amino-4Ј-O-demethylepipodophyllotoxin] had inhibitory activity against TOP I and TOP II with IC 50 values 1.5-fold higher than either CPT or etoposide (VP-16). Both conjugates had similar cytotoxicity against the KB cell line, although the protein-linked DNA breaks (PLDBs) generated by W2 in KB cells were about 4-fold more than those of W1. No cross-resistance with the two conjugates was seen in a VP-16-resistant KB subline, which showed down-regulation of TOP II and overexpression of the multiple drug resistance-associated protein, or in a vincristine-resistant KB subline with overexpression of gp-170/mdr-1. The CPT-resistant KB variant (KB CPT 100), which has a reduction in TOP I content and another mechanism that occurs post-PLDB formation, was partially resistant to both compounds. W1 was not affected by this post-PLDB resistance mechanism. Cell cycle analysis demonstrated that W1 and W2 had similar cell cycle effects on KB and KB CPT 100 cells, which accumulated in S-phase upon drug treatment. These results suggested that W1 and W2 exerted their cytotoxicity through TOP I. In CPT-resistant cells, however, an unidentified target also may be involved in the cytotoxic action of W1, and TOP II may still be a target for W2. In vivo, W1 was more effective against the growth of human prostate cancer cells in nude mice than VP-16, CPT, or W2. Given its antitumor activity and unique biochemical mechanism of action, W1 warrants exploration as an antitumor compound.
Lebensmittel-Wissenschaft & Technologie, Mar 1, 2019
The aim was to establish a rapid and quantitative detection method of formaldehyde in squid based... more The aim was to establish a rapid and quantitative detection method of formaldehyde in squid based on electronic nose for screening massive samples. Identification of volatile compounds in squid with different formaldehyde content by electronic nose were mainly depended on eight sensors. Besides, the diversities of volatile constituents in squid with increasing contents of aldehydes and aromatic compounds were validated by GC-MS results. Moreover, to build a qualitative discrimination model for estimating whether formaldehyde in squid over standard limit or not, DFA and SIMCA based on PCA were used to analyze electronic nose data for semi-quantitative determination of formaldehyde content in squid. Finally, a rapid quantitative prediction model based on electronic nose and PLS was established (R 2 =0.9266).To verify the accuracy of quantitative model, t-test was employed and no significant difference between predicted values and true values was found. This approach showed well potentiality to provide a rapid, nondestructive and quantitative method for detecting formaldehyde residue in food.
YIV-906 (PHY906) is a standardized botanical cancer drug candidate developed with a systems biolo... more YIV-906 (PHY906) is a standardized botanical cancer drug candidate developed with a systems biology approach-inspired by a traditional Chinese herbal formulation, historically used to treat gastrointestinal symptoms including diarrhea, nausea and vomiting. In combination with chemotherapy and/or radiation therapy, preclinical and clinical results suggest that YIV-906 has the potential to prolong survival and improve quality of life for cancer patients. Here, we demonstrated that YIV-906 plus anti-PD1 could eradicate all Hepa 1-6 tumors in all tumor bearing mice. YIV-906 was found to have multiple mechanisms of action to enhance adaptive and innate immunity. In combination, YIV-906 reduced PD1 or counteracted PDL1 induction caused by anti-PD1 which led to higher T-cell activation gene expression of the tumor. In addition, YIV-906 could reduce immune tolerance by modulating IDO activity and reducing monocytic MDSC of the tumor. The combination of anti-PD1 and YIV-906 generated acute in ammation in the tumor microenvironment with more M1-like macrophages. YIV-906 could potentiate the action of IFNg to increase M1-like macrophage polarization while inhibiting IL4 action to decrease M2 macrophage polarization. Flavonoids from YIV-906 were responsible for modulating IDO activity and potentiating IFNg action in M1-like macrophage polarization. In conclusion, YIV-906 could act as an immunomodulator and enhance the innate and adaptive immune response and potentiate anti-tumor activity for immunotherapies to treat cancer.
2145 PHY906, a traditional Chinese botanical formulation, was first described 1800 years ago for ... more 2145 PHY906, a traditional Chinese botanical formulation, was first described 1800 years ago for common gastrointestinal distress. Currently, PHY906 is being developed for FDA approval as a botanical prescription medicine offering a new approach to cancer supportive care. The preclinical data indicates that PHY906 can reduce chemo-induced gastrointestinal toxicity while simultaneously enhancing the therapeutic efficacy of a broad-spectrum of common anticancer agents, including CPT-11, 5-FU, capecitabine, oxaliplatin, VP-16, taxol, and gemcitabine in a variety of tumor-implanted in vivo animal models. The mechanism of PHY906 antitumor activity is multifarious, including inhibitory activities of NF-κB, matrix metalloproteases (MMPs), multi-drug resistant protein (MDR), and CYP450 and modulation of numerous cytokines. Possible mechanisms of action for the reduction of gastrointestinal toxicity are the inhibition of Tachykinin NK-1 and Opiate δ receptors and modulation of inflammatory cytokines. A phase I/II, multicenter, open-label, dose-escalation, safety and efficacy study of PHY906 plus capecitabine in patients with unresectable hepatocellular carcinoma is presently underway. The main objective of phase I is to define the safety, tolerability, and effective dose of PHY906 when co-administered with capecitabine. Three doses have been studied. Cohort I: PHY906 (1000mg, bid, D1-4 and 8-11) plus capecitabine (1000 mg/m2,bid, D1-14); cohort II: PHY906 (600mg, bid, D1-4 and 8-11) plus capecitabine (750 mg/m2, bid, D1-14); and cohort III: PHY906 (800mg, bid, D1-4 and 8-11) plus capecitabine (750 mg/m2, bid, D1-14). The cohort I dose regimen has resulted in unacceptable dose-limiting toxicities while the dosing in cohorts II and III were both well tolerated. Stable disease after two cycles of study-drug treatment for cohorts II (N=4) and III (N=6) are 75% and 67%, respectively. The median time to disease progression (TTP) is 26.5 weeks and the median survival time is greater than 44.5 weeks for Cohort II. The majority of the patients in Cohort III remain on study. The primary objective for the current phase II is determining the objective antitumor response rate while the secondary objectives are determining TTP, overall survival time, and quality of life (QoL). While clinical trials address efficacy and safety of the drug, chemical and biological analytic methods have been developed to address drug consistency and quality control. Comprehensive molecular resolution chemical fingerprints utilizing a three-dimensional LC/MS profile and a sensitive cellular bioresponse genomic profile to generate a quantitative signature pattern for comparing and confirming batch-to-batch similarity of study drug. These studies offer a modern approach to the study of ancient botanicals that may represent novel regimens for cancer treatment.
557 PHY906 is a traditional Chinese botanical formulation consisting of 4 different herbs, and it... more 557 PHY906 is a traditional Chinese botanical formulation consisting of 4 different herbs, and it has been used for some 1800 years to treat gastrointestinal ailments, some of which are commonly observed side effects in cancer patients undergoing chemotherapy. We have previously reported that PHY906 reduced chemotherapy-induced toxicities including body weight loss and mortality, and that it also enhanced the antitumor efficacy of a broad-spectrum of anticancer agents, such as CPT-11, 5-FU, CPT-11/5-FU/LV, VP-16, and L-OddC in in vivo animal models. PHY906 has been co-administrated with either the oral 5-FU prodrug capecitabine or CPT-11 in human hepatocellular xenografts mouse model, and with gemcitabine in mouse pancreatic cancer model. We have shown that PHY906 significantly enhanced the therapeutic index of chemotherapeutic agents studied in both hepatocellular and pancreatic cancer models. Co-administration of PHY906 with either capecitabine or gemcitabine in animal models did not alter the pharmacokinetic profile of capecitabine, gemcitabine, or their respective metabolites. Our biochemical studies revealed that the PHY906 formulation possesses a wide range of pharmacological activities. The potential mechanism(s) of action of PHY906 include (1) enhancement of oral uptake of pharmacologically active agents with inhibition in intestinal CYP3A4; (2) inhibition of NF-κB activity; (3) inhibition of MMP activity; and (4) destruction of the integrity of sinusoids in hepatoma. These pre-clinical in vivo studies have provided rationale for developing PHY906 in the clinical setting. A phase I/IIA double-blind placebo-controlled, dose escalation study of PHY906 was initiated to evaluate the potential effect of PHY906 in modulating CPT-11-induced diarrhea associated with the bolus, weekly schedule of CPT-11/5-FU/LV in advanced colorectal cancer patients. A second phase I/II open-label dose escalation clinical trial has just been opened to patient accrual to evaluate the role of PHY906 in combination with capecitabine in the treatment of hepatocellular carcinoma.
Background-: Traditional Chinese Medicine (TCM) has been used for thousands of years to treat or ... more Background-: Traditional Chinese Medicine (TCM) has been used for thousands of years to treat or prevent diseases, including cancer. Good manufacturing practices (GMP) and sophisticated product analysis (PhytomicsQC) to ensure consistency are now available allowing the assessment of its utility. Polychemical Medicines, like TCM, include chemicals with distinct tissue-dependent pharmacodynamic properties that result in tissue-specific bioactivity. Determining the mode of action of these mixtures was previously unsatisfactory; however, information rich RNA microarray technologies now allow for thorough mechanistic studies of the effects complex mixtures. PHY906 is a long used four herb TCM formula employed as an adjuvant to relieve the side effects associated with chemotherapy. Animal studies documented a decrease in global toxicity and an increase in therapeutic effectiveness of chemotherapy when combined with PHY906. Methods-: Using a systems biology approach, we studied tumor tissu...
Cette invention porte sur des compositions vegetales utiles pour augmenter l'indice therapeut... more Cette invention porte sur des compositions vegetales utiles pour augmenter l'indice therapeutique de composes chimiotherapeutiques. Cette invention porte egalement sur des procedes utiles pour ameliorer la qualite de vie d'un patient subissant une chimiotherapie. De plus, cette invention ameliore le traitement d'un cancer par l'administration de la composition vegetale PHY906 en combinaison avec un ou plusieurs composes chimiotherapeutiques chez un mammifere subissant une telle chimiotherapie.
2145 PHY906, a traditional Chinese botanical formulation, was first described 1800 years ago for ... more 2145 PHY906, a traditional Chinese botanical formulation, was first described 1800 years ago for common gastrointestinal distress. Currently, PHY906 is being developed for FDA approval as a botanical prescription medicine offering a new approach to cancer supportive care. The preclinical data indicates that PHY906 can reduce chemo-induced gastrointestinal toxicity while simultaneously enhancing the therapeutic efficacy of a broad-spectrum of common anticancer agents, including CPT-11, 5-FU, capecitabine, oxaliplatin, VP-16, taxol, and gemcitabine in a variety of tumor-implanted in vivo animal models. The mechanism of PHY906 antitumor activity is multifarious, including inhibitory activities of NF-κB, matrix metalloproteases (MMPs), multi-drug resistant protein (MDR), and CYP450 and modulation of numerous cytokines. Possible mechanisms of action for the reduction of gastrointestinal toxicity are the inhibition of Tachykinin NK-1 and Opiate δ receptors and modulation of inflammatory c...
e13571 Background: The goal of this phase I study was to determine the maximum tolerated dose (MT... more e13571 Background: The goal of this phase I study was to determine the maximum tolerated dose (MTD) of the oral Chinese herbal medication PHY906 when combined with CPT-11. PHY906 has been used in A...
Panax notoginseng (Burk.) F.H.Chen is a well known Chinese medicinal plant. Its radix is used in ... more Panax notoginseng (Burk.) F.H.Chen is a well known Chinese medicinal plant. Its radix is used in the history while its flower is recently used for health care. In this study we compared chemical ingredients and bioactivities in cell culture for radix and flower of Panax notoginseng (Burk.) F.H.Chen. The liquid chromatography-mass spectrometry system was applied to determine the contents of saponins in flower and radix of Panax notoginseng (Burk.) F.H.Chen. Transcription specific luciferase reporter assay and qPCR method for selected RNA were carried out to assess the impacts of flower and radix extract on the transcription signal pathways. The results of chemical analysis showed that the contents of saponins in flower and radix are very different: the contents of Rg1, Rb1, Re, R1, Rg3-20R, Rh1 and Rf in radix are abundant; in contrast, the contents of Rb3, Fc, Ft1, Rb2 and Rh2-20s in flowers are plentiful. There are substantial variations of those saponin contents from one batch vs ...
YIV-906 (PHY906) is a standardized botanical cancer drug candidate developed with a systems biolo... more YIV-906 (PHY906) is a standardized botanical cancer drug candidate developed with a systems biology approach—inspired by a traditional Chinese herbal formulation, historically used to treat gastrointestinal symptoms including diarrhea, nausea and vomiting. In combination with chemotherapy and/or radiation therapy, preclinical and clinical results suggest that YIV-906 has the potential to prolong survival and improve quality of life for cancer patients. Here, we demonstrated that YIV-906 plus anti-PD1 could eradicate all Hepa 1–6 tumors in all tumor bearing mice. YIV-906 was found to have multiple mechanisms of action to enhance adaptive and innate immunity. In combination, YIV-906 reduced PD1 or counteracted PD-L1 induction caused by anti-PD1 which led to higher T-cell activation gene expression of the tumor. In addition, YIV-906 could reduce immune tolerance by modulating IDO activity and reducing monocytic MDSC of the tumor. The combination of anti-PD1 and YIV-906 generated acute ...
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