Synergy of de-walled Ganoderma Lucidum spore powder (GLSP) on targeted therapy in advanced non-squamous non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutant: protocol for a randomized, double-blind, placebo-controlled study.

BACKGROUND: Osimertinib is regarded as a promising third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) for advanced non-squamous non-small cell lung cancer (NSCLC) patients who developed T790M. However the adverse effects, primarily fatigue, remain an overwhelming deficiency of Osimertinib, hindering it from achieving adequate clinical efficacy for such NSCLC. Ganoderma lucidum has been used for thousands of years in China to combat fatigue, while Ganoderma Lucidum spores powder (GLSP) is the main active ingredient. The aim of this study is to investigate whether GLSP is sufficiently effective and safe in improving fatigue and synergizing with Osimertinib in non-squamous NSCLC patients with EGFR mutant. METHOD/DESIGN: A total of 140 participants will be randomly assigned to receive either de-walled GSLP or placebo for a duration of 56 days. The primary outcome measure is the fatigue score associated with EGFR-TKI adverse reactions at week 8, evaluated by the Chinese version of the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire for Cancer Patients (QLQ-C30). Secondary outcomes include evaluation of treatment effectiveness, assessment of quality of life (QoL), and exploration of immune indicators and gut microbiota relationships. Following enrollment, visits are scheduled biweekly until week 12. TRIAL REGISTRATION: China Clinical Trial Registry ChiCTR2300072786. Registrated on June 25, 2023.

Huayu Pill () Promotes Fluorescent Doxorubicin Delivery to Tumors in Mouse Model of Lung Cancer.

OBJECTIVE: To study the effect and mechanism of Huayu Wan (, HYW) in combination of chemotherapy of tumor treatment. METHODS: HYW serum was added in Lewis cells to assess its impact on fluorescent doxorubicin delivery in vitro. Then, Lewis tumor cells was implanted in C57BL/6 mice via xenograft transplantation. Tumor growth was measured and signal intensity corresponding to blood flow was assessed by laser doppler perfusion imaging (LDPI). Finally, the effect of HYW on the effificacy of doxorubicin was studied. RESULTS: HYW can improve the transfer of fluorescent doxorubicin into cells. The blood flow signal in the tumor tissues of the HYW group was higher than that of the control group (P<0.01). Furthermore, HYW improved drug delivery of doxorubicin to tumor tissues, and this activity was associated with HYW-induced microvascular proliferation (P<0.01). CONCLUSIONS: HYW can promote microangiogenesis and increase blood supply in tumor tissues, which in turn may increase the risk of metastasis. At the same time, HYW increases drug delivery and improves the effificacy of chemotherapy drugs through vascular proliferation. Therefore, rational judgment must be exercised when considering applying HYW to an antitumor regimen.

SANT, a novel Chinese herbal monomer combination, decreasing tumor growth and angiogenesis via modulating autophagy in heparanase overexpressed triple-negative breast cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Astragalus mongholicus, Solanum nigrum Linn, Lotus plumule, Ligusticum are widely used traditional herbal medicines for cancer treatment in China. They were typical drugs selected from Gubenyiliu II and series of formula (GYII), which were developed on the foundation of YIQIHUOXUEJIEDU theory. In the present study, four active ingredients (Astragaloside IV, α-solanine, neferine, and 2,3,5,6-tetramethylpyrazine) derived from medicines above were applied in combination as SANT. AIM OF THE STUDY: Triple-negative breast cancer (TNBC) is a serious threat to women's health worldwide. Heparanase (HPSE) is often up-regulated in breast cancer with the properties of facilitating tumorigenesis and influencing the autophagy process in cancer cells. This study aimed at evaluating the anti-tumor potential of SANT in treating HPSE related TNBC both in-vitro and in-vivo. MATERIALS AND METHODS: In this study, we explored the correlation between HPSE expression and survival of breast cancer patients in databases. We performed MTS, trans-well and wound scratch assays to assess the impact of SANT on cell proliferation and migration. Confocal microscopy observation and western blots were applied to verify the autophagy flux induced by SANT. Mice models were employed to evaluate the efficacy and safety of SANT in-vivo by tumor weights and volumes or serum index, respectively. To analyze the underlying mechanisms of SANT, we conducted human autophagy PCR array and angiogenesis proteome profiler on tumor tissues. RESULTS: Patients with elevated HPSE expression were associated with a poor outcome in both RFS (P = 1.7e-12) and OS (P = 0.00016). SANT administration significantly inhibited cancer cells' proliferation and migration, enhanced autophagy flux, and slightly reduced the active form of HPSE in-vitro. SANT also suppressed tumor growth and angiogenesis in-vivo. Human autophagy PCR array results indicated that SANT increased the ATG16L1, ATG9B, ATG4D gene expressions while decreased TMEM74 and TNF gene expressions.Angiogenesis proteome profiler results showed SANT reduced protein level of HB-EGF, thrombospondin-2, amphiregulin, leptin, IGFBP-9, EGF, coagulation factor III, and MMP-9 (pro and active form) in tumor, raised the protein expression of serpin E1 and platelet factor 4. CONCLUSIONS: These findings indicated that herbal compounds SANT may be a promising candidate in anti-cancer drug discovery. It also provides novel strategies for using natural compounds to achieve optimized effect.

Efficacy of acupuncture in the prevention and treatment of chemotherapy-induced nausea and vomiting in patients with advanced cancer: a multi-center, single-blind, randomized, sham-controlled clinical research.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is a common and distressing side effect. We conducted this clinical trial to compare the effectiveness of true acupuncture vs. sham acupuncture in controlling chemotherapy-induced nausea and vomiting (CINV) among patients with advanced cancer. METHODS: A total of 134 participants were randomly allocated into true acupuncture (TA) (n = 68) and sham acupuncture (SA) (n = 66) groups. Participants in both groups received acupuncture session twice on the first day of chemotherapy, and once consecutively on the following 4 days. The primary outcome was using the Common Terminology Criteria for Adverse Events (CTCAE) to assess CINV. The secondary outcome measures were the Eastern Cooperative Oncology Group score (ECOG), Simplified Nutritional Appetite Questionnaire (SNAQ), and Hospital Anxiety and Depression scale (HADS). RESULTS: Compared to the SA group, the TA group didn't show significant improvement in complete response rates of chemotherapy-induced nausea and vomiting (all P > 0.05). However, the TA group could modestly reduce the severity of nausea (from day-3 to day-21, P < 0.05) or vomiting (from day-4 to day-21, P < 0.05), which is notably superior to the control group. Besides, TA promoted the nutritional status of patients with a significantly higher score comparing to the SA group on day 14 (21.82 vs.20.12, P = 0.003) and day 21 (22.39 vs. 20.43, P = 0.001). No apparent differences were found in anxiety and depression assessment between these groups. Participants in both groups were well tolerant of acupuncture therapy. There was no adverse event occurs in our study. CONCLUSION: Acupuncture as an adjunctive approach could alleviate the severity of chemotherapy-induced nausea and vomiting compared to the sham control, even though the effect of acupuncture in preventing CINV occurring is relatively modest.

Scutellaria barbata and Hedyotis diffusa herb pair for breast cancer treatment: Potential mechanism based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: The Scutellaria barbata and Hedyotis diffusa (SH) herb pair is extensively used in Traditional Chinese Medicine for efficacy enhancement in cancer treatment in China and Asian countries. Superior clinical efficacy observations based on high dosages (≥60 g) motivated us to explore appropriate dosages and the underlying mechanisms of action. AIM OF THE STUDY: To explore the efficacy and potential mechanisms of actions of SH through in vitro and in vivo experiments and network pharmacology. MATERIALS AND METHODS: SH lyophilized powder (SHLP) was prepared from decoctions and the active ingredients were identified using high performance liquid chromatography (HPLC). Proliferation and migration experiments in vitro and tumor growth in vivo were performed to evaluate the effects of SHLP on breast cancer. Corresponding potential target genes for SHLP components and breast cancer were extracted from established databases and the Protein-Protein Internetwork of shared genes were constructed using STRING database. Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation clusters were acquired and the top 30 pathways were presented. At last, as one of pathways indicated by enriched results, apoptosis was validated with flow cytometric analysis and caspase-3, 8, 9 activities. RESULTS: Seventy-five ingredients were identified from SHLP by HPLC. High SHLP doses inhibited proliferation and migration of three types of breast cancer cells in vitro and tumor growth in nude mice. After target genes extraction and intersection, the top 30 KEGG clusters were enriched, including PI3K-Akt, cell cycle and other related pathways like VEGF, Micro-RNAs and NF-κB, besides, key genes in apoptosis were mapped. In the last, apoptosis was validated by flow cytometric analysis and caspase-3, 8, 9 activities after SHLP treatment. CONCLUSION: High SHLP dosages inhibited breast cancer in vitro and in vivo, enriched by network pharmacology and confirmed by flow cytometric analysis and caspase activation, with apoptosis was identified as one of the mechanisms of action of SHLP. SHLP administration with higher doses is recommended for clinical usage.

A network-based predictive gene expression signature for recurrence risks in stage II colorectal cancer.

The current criteria for defining the recurrence risks of stage II colorectal cancer (CRC) are not robust; therefore, we aimed to explore novel gene signatures to predict recurrence risks and to reveal the underlying mechanisms of stage II CRC. First, the gene expression profiles of 124 patients with stage II CRC from The Cancer Genome Atlas (TCGA) database were obtained to screen differentially expressed genes (DEGs). A total of 202 DEGs, including 128 upregulated and 74 downregulated, were identified in the recurrence group (n = 24) compared to the nonrecurrence group (n = 100). Furthermore, the top 5 DEGs (ZNF561, WFS1, SLC2A1, MFI2, and PTGR1) were identified by random forest variable hunting, and four (ZNF561, WFS1, SLC2A1, and PTGR1) were selected to create a four-gene recurrent model (GRM), with an area under the curve (AUC) of 0.882 according to the receiver operating characteristic curve, and the robust diagnostic effectiveness of the GRM was further validated with another gene expression profiling dataset (GSE12032), with an AUC of 0.943. The diagnostic effectiveness of the GRM regarding recurrence was associated with poor disease-free survival in all stages of CRC. In addition, gene ontology functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses revealed 18 enriched functions and 6 enriched pathways. Four genes, ABCG2, CACNA1F, CYP19A1, and TF, were identified as hub genes by the protein-protein interaction network, which further validated that these genes were correlated with a poor pathologic stage and overall survival in all stages of CRC. In conclusion, the GRM can effectively classify stage II CRC into groups of high and low risks of recurrence, thereby making up for the prognostic value of the traditional clinicopathological risk factors defined by the National Comprehensive Cancer Network guidelines. The hub genes may be useful therapeutic targets for recurrence. Thus, the GRM and hub genes could offer clinical value in directing individualized and precision therapeutic regimens for stage II CRC patients.

Chinese Medicine Yishen Jiangu Granules () on Aromatase Inhibitor-Associated Musculoskeletal Symptoms.

OBJECTIVE: To assess the effectiveness of Yishen Jiangu Granules (, YSJGG) on aromatase inhibitor-associated musculoskeletal symptoms (AIMSS). METHODS: A single-arm, open-label study was conducted in 34 postmenopausal women with breast cancer who experienced AIMSS. Patients were treated with YSJGG for 12 weeks (12.4 g orally twice daily). The primary outcome was a change in the mean worst pain score of Brief Pain Inventory-Short Form (BPI-SF) over 12 weeks, and the second outcomes included changes in pain severity and pain-related interference of BPI-SF and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Modified Score for the Assessment of Chronic Rheumatoid Affections of the Hands (M-SACRAH), the Functional Assessment of Cancer Therapy-Breast (FACT-B), bone mineral density (BMD) and blood indices such as calcium (Ca), phosphate (P), and alkaline phosphatase (ALP). RESULTS: Of 37 women recruited, 30 initiated the therapy and 24 were evaluable at 12 weeks. The primary outcome (BPI-SF worst pain scores) achieved a 2.17-point reduction compared with baseline (5.75±1.87 vs 3.58±2.15, P<0.01). There were reductions in pain severity (decreased 1.65, P<0.01) and pain-related interference (decreased 2.55, P<0.01). The changes in WOMAC and M-SACRAH scores were similar to BPI-SF (P<0.05). In the FACT-B, only physical well-being and functional well-being were improved compared with baseline (P<0.05). No clinical differences were found in BMD, Ca, P and ALP. CONCLUSION: YSJGG is an effective and well-tolerated agent to reduce AIMSS.

Gubenyiliu II Inhibits Breast Tumor Growth and Metastasis Associated with Decreased Heparanase Expression and Phosphorylation of ERK and AKT Pathways.

Gubenyiliu II (GYII), a Traditional Chinese Medicine (TCM) formula used in our hospital, has shown beneficial effects in cancer patients. In this study, we investigated the molecular mechanisms underlying the beneficial effects of GYII on murine breast cancer models. GYII showed significant inhibitory effects on tumor growth and metastasis in the murine breast cancer model. Additionally, GYII suppressed the proliferation of 4T1 and MCF-7 cells in a dose-dependent manner. A better inhibitory effect on 4T1 cell proliferation and migration was found in the decomposed recipes (DR) of GYII. Moreover, heparanase expression and the degree of angiogenesis were reduced in tumor tissues. Western blot analysis showed decreased expression of heparanase and growth factors in the cells treated with GYII and its decomposed recipes (DR2 and DR3), and thereby a reduction in the phosphorylation of extracellular signal-regulated kinase (ERK) and serine-threonine kinase (AKT). These results suggest that GYII exerts anti-tumor growth and anti-metastatic effects in the murine breast cancer model. The anti-tumor activity of GYII and its decomposed recipes is, at least partly, associated with decreased heparanase and growth factor expression, which subsequently suppressed the activation of the ERK and AKT pathways.

EFFECT OF RUANGANJIEDU DECOCTION INHIBIT EXPERIMENTAL HEPATIC FIBROSIS OF RATS.

BACKGROUND: RuanGanJieDu (RGJD) is a traditional Chinese medicine comprising nine Chinese medicinal herbs. The clinical use of RGJD by us was found that it has a good control effect on hepatic fibrosis (HF) patient. In order to further investigate the Anti-fibrosis mechanism of RGJD, hence this experiment has been carried out. METHODS: After treatment, the general conditions of rats in each group were observed. The liver tissues morphology and HF phases were observed under light microscope. The weights of livers and spleens were recorded; the indices of liver and spleen were calculated. The α-SMA and E-cadherin of the liver tissues were determined by Immunohistochemistry, and the contents of ALT AST and PCIII+PCIV+HA+LN in rat serum were detected by ELISA. RESULTS: After treatment, the rats in model group presented with abdominal distention and rough hair, lethargy and mental sluggishness, slow movement and irritability; Most rats in RGJD group and colchicine(Col) group were in good spirits and no obvious abnormal motion state. The RGJD had shown significant effects in improving the liver tissue morphology. The HF phases of RGJD group and Col group mainly distributed in the S1-S2 phases, were finer than the model group in the S3 phase (P<0.05). The wet weights and indices of livers and spleens in RGJD group were lower than the control groups (P<0.05). Moreover, the expressions of E-cadherin, α-SMA and the serum levels of AST, ALT and PCIII+ PCIV in RGJD group were obviously decreased than the control groups except HA and LN(P<0.05). CONCLUSION: RGJD can improve the liver tissue morphology and reduce serum biochemical and collagen indices of HF, which proved a better curative effect of Chinese medicine than Col on HF and improving liver function.

Effect of acupuncture in prevention and treatment of chemotherapy-induced nausea and vomiting in patients with advanced cancer: study protocol for a randomized controlled trial.

BACKGROUND: Chemotherapy-induced nausea and vomiting (CINV) is one of the most common and distressing side effects in patients with cancer. The introduction and development of antiemetic drugs have significantly improved the ability of clinicians to control CINV, but it is not easy to translate to practical application, owing to financial issues, provider-related barriers, and patient factors. Nondrug therapies are needed to alleviate the symptoms of CINV. Acupuncture is an appropriate adjunctive treatment for CINV, but additional evidence is needed. METHODS/DESIGN: This study is a multicenter, randomized, sham-controlled prospective clinical trial. A total of 136 participants will be randomly allocated into the intervention group (verum acupuncture) or the control group (sham acupuncture) in a 1:1 ratio. All treatment will be given for 5 days. Participants in both groups will receive acupuncture sessions twice on the first day of chemotherapy and once consecutively on the following 4 days. Each session takes approximately 30 minutes. The primary outcome measure will be the Common Terminology Criteria for Adverse Events to assess CINV. The secondary outcome measures will be the Eastern Cooperative Oncology Group score, Simplified Nutritional Appetite Questionnaire, and Hospital Anxiety and Depression scale. Safety will be assessed at each visit. DISCUSSION: The results of this trial will provide clinical evidence for the effect and safety of acupuncture for CINV. TRIAL REGISTRATIONS: ISRCTN Registry identifier: ISRCTN13287728 ). Registered on 28 February 2015. ClinicalTrials.gov identifier: NCT02369107 . Registered on 17 February 2015.

Chinese Herbal Medicine as Adjunctive Therapy to Chemotherapy for Breast Cancer: A Systematic Review and Meta-Analysis.

Chinese herbal medicine (CHM) has been increasingly employed during therapy for breast cancer, but its efficacy remains a matter of debate. This systematic review examined randomized controlled trials to provide a critical evaluation of this treatment. The results demonstrated that the combined use of CHM with chemotherapy may improve the immediate tumor response and reduce chemotherapy-associated adverse events. Our findings highlight the poor quality of Chinese studies, and additional well-designed randomized controlled trials addressing the role of CHM are warranted. The lack of molecular-based evidence for CHM and Zheng has resulted in a limited understanding and acceptance of CHM and traditional Chinese medicine in Western countries. We believe that researchers should immediately explore a CHM-based cure, and CHM should be applied to routine care as soon as conclusive data are available.

Heijiangdan ointment relieves oxidative stress from radiation dermatitis induced by (60)Co γ-ray in mice.

OBJECTIVE: To investigate the effects of Heijiangdan Ointment ( HJD) on oxidative stress in (60)Co γ-ray radiation-induced dermatitis in mice. METHODS: Female Wistar mice with grade 4 radiation dermatitis induced by (60)Co γ-rays were randomly divided into four groups (n=12 per group); the HJD-treated, recombinant human epidermal growth factor (rhEGF)-treated, Trolox-treated, and untreated groups, along with a negative control group. On the 11th and 21st days after treatment, 6 mice in each group were chosen for evaluation. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), and lactate dehydrogenase (LDH) were detected using spectrophotometric methods. The fibroblast mitochondria were observed by transmission electron microscopy (TEM). The expressions of fibroblast growth factor 2 (FGF-2) and transforming growth factor ß1 (TGF-ß1) were analyzed by western blot. RESULTS: Compared with the untreated group, the levels of SOD, MDA and LDH, on the 11th and 21st days after treatment showed significant difference (P<0.05). TEM analysis indicated that fibroblast mitochondria in the untreated group exhibited swelling and the cristae appeared fractured, while in the HJD group, the swelling of mitochondria was limited and the rough endoplasmic reticulum appeared more relaxed. The expressions of FGF-2 and TGF-ß1 increased in the untreated group compared with the negative control group (P<0.05). After treatment, the expression of FGF-2, rhEGF and Trolox in the HJD group were significantly increased compared with the untreated group (P<0.05), or compared with the negative control group (P<0.05). The expression of TGF-ß1 showed significant difference between untreated and negative control groups (P<0.05). HJD and Trolox increased the level of TGF-ß1 and the difference was marked as compared with the untreated and negative control groups (P<0.05). CONCLUSION: HJD relieves oxidative stress-induced injury, increases the antioxidant activity, mitigates the fibroblast mitochondrial damage, up-regulates the expression of growth factor, and promotes mitochondrial repair in mice.

Traditional Chinese medical comprehensive therapy for cancer-related fatigue.

Cancer-related fatigue (CRF) is a common and one of the most severe symptom in the period of onset, diagnosis, treatment and rehabilitation process of cancer. But there are no confirmed measures to relieve this problem at present. Traditional Chinese medical comprehensive therapy has its advantages in dealing with this condition. Based on the research status of CRF, the following problems have been analyzed and solved: the term of CRF has been defined and recommended, and the definition has been made clear; the disease mechanism is proposed, i.e. healthy qi has been impaired in the long-term disease duration, in the process of surgery, chemotherapy, radiotherapy and biology disturbing; it is clear that the clinical manifestations are related to six Chinese medicine patterns: decreased functioning of the Pi (Spleen) and Wei (Stomach), deficiency of the Pi with dampness retention, deficiency of the Xin (Heart) and Pi, disharmony between the Gan (Liver) and Pi, deficiency of the Pi and Shen (Kidney), and deficiency of the Fei (Lung) and Shen. Based on its severity, the mild patients are advised to have non-drug psychological intervention and sleep treatment in cooperation with appropriate exercise; diet therapy are recommended to moderate patients together with sleep treatment and acupuncture, severe patients are recommended to have herbal treatment based on pattern differentiation together with physiological sleep therapy.

Effects of the traditional Chinese medicine Yi Shen Jian Gu granules on aromatase inhibitor-associated musculoskeletal symptoms: a study protocol for a multicenter, randomized, controlled clinical trial.

BACKGROUND: Aromatase inhibitors (AIs) are widely used as an adjuvant endocrine treatment in postmenopausal women with early-stage breast cancer. One of the main adverse effects of AIs is musculoskeletal symptoms, which leads to a lower quality of life and poor adherence to AI treatment. To date, no effective management of aromatase inhibitor-associated musculoskeletal symptoms (AIMSS) has been developed. METHODS/DESIGN: To determine whether the traditional Chinese medicine Yi Shen Jian Gu granules could effectively manage AIMSS we will conduct a multicenter, randomized, double-blind, placebo-controlled clinical trial. Patients experiencing musculoskeletal symptoms after taking AIs will be enrolled and treated with traditional Chinese medicine or placebo for 12 weeks. The primary outcome measures include Brief Pain Inventory-Short Form, Western Ontario and McMaster Universities Osteoarthritis Index, and Modified Score for the Assessment and Quantification of Chronic Rheumatoid Affections of the Hands, which will be obtained at baseline and at 4, 8, 12 and 24 weeks. DISCUSSION: The results of this study will provide a new strategy to help relieve AIMSS. TRIAL REGISTRATION ISCTN: ISRCTN06129599 (assigned 14 August 2013).

Action mechanism of fuzheng fangai pill combined with cyclophosphamide on tumor metastasis and growth.

Fuzheng Fangai pill (FZFA), a traditional Chinese formula, is widely used for cancer treatment. Compared with other anticancer drugs, it is characterized by moderate and persistent efficacy with few side effects. The present paper emphasizes antitumor effect of FZFA combined with cyclophosphamide (CTX) on C57BL/6 mice subcutaneously injected with Lewis lung cancer cells, Comparing it with that of CTX. On the 21st day, a set of biochemical parameters were studied: the tumor weight and tumor volume, the inhibition rate of lung metastasis, the percentage and ratio of spleen CD4(+)IL-17(+) Th17 (T helper cell 17, Th17 for short) and CD4(+)CD25(+)Foxp3(+) Treg (T regulatory cell, Treg for short) cells, and the concentrations of IL-6, TGF- ß , IL-17, IL-23, and IFN- γ in culture supernatants of CD4(+) T lymphocytes were determined. The expression of the splenic Foxp3 and ROR γ t mRNA and JAK2, STAT3, and SOCS3 protein as also determined. The results show that compared with the model control group and CTX group, FZFA+CTX restored the ratio of spleen CD4(+)IL-17(+) Th17 and CD4(+)CD25(+) Foxp3(+) Treg cells, and inhibited the inflammatory response including the nuclear SOCS3/JAK-STAT pathway, regulation of interleukins TGF- ß , IL-6, IL-17, IL-23, and IFN- γ , and Foxp3 and ROR γ t gene expression in CD4(+) T lymphocytes. We conclude that FZFA+CTX strongly reduced the growth and metastasis rate of Lewis lung cancer through inhibition of SOCS/JAK-STAT pathway and inflammatory cytokine responses. FZFA + CTX had greater activity than CTX alone.