Category Archives: Fatigue

Anti-metastatic, Chapter 8 Injectables and Cancer Research, Chemotherapy, chemotherapy support, Fatigue, Immune, Lung cancer, Nausea and Vomiting, radiotherapy

Shen qi fu zheng (Vital-qi Fortify)

Cancers: Stomach, lung

Action: Anti-metastatic, chemotherapy support

Ingredients: dang shen (Codonopsis pilosula), huang qi (Astragalus membranaceus).

TCM functions: Invigorating qi and supporting Vital-qi,

Indications: Adjuvant treatment for late-stage lung cancer not suitable for radiotherapy or chemotherapy, of qi deficiency type. It can be combined with chemotherapy for the adjuvant treatment of lung cancer and stomach cancer of qi deficiency type.

Dosage and usage:

Combination with radiotherapy or chemotherapy: Be administrated 3 days before chemotherapy, then be used synchronously with chemotherapy. 1 bottle daily for intravenous drip. The course is the same as that of radiotherapy or chemotherapy.

The clinical efficacy of Shenqifuzheng injection, combined with Bozhi glycopeptide, in treating aged lung cancer patients was observed.

NSCLC; Chemotherapy

In China, Shenqi Fuzheng, a newly developed injection concocted from Chinese medicinal herbs has been reported that may increase efficacy and reduce toxicity when combined with platinum-based chemotherapy, but little is known about it outside of China.

Twenty nine studies were included in this review based on our selection criteria. Of them, ten studies were of high quality and the rest were of low quality, according to the modified Jadad scale. The meta-analysis showed there was a statistically significant higher tumor response when the SFI plus platinum-based chemotherapy treatment group was compared with the platinum-based chemotherapy control group (Dong et al., 2010).

NSCLC

Sixty patients with advanced non-small-cell lung cancer were randomly divided into a treatment group or control group. The treatment group was treated by Shenqi Fuzheng injection combined with chemotherapy, and the control group with chemotherapy alone.

The effect of Shenqi Fuzheng injection combined with chemotherapy vs the chemotherapy alone showed no significant difference. However, in reducing toxicity and side-effects of chemotherapy, such as gastrointestinal reaction and leukopenia, it was superior to the chemotherapy alone (P < 0. 05).

The effect of Shenqi Fuzheng injection combined with chemotherapy in the treatment of advanced non-small-cell lung cancer can improve the quality of life of patients, reduce the toxic side-effects of chemotherapeutic agents, and enhance immunity (Qiao, 2012).

Lung Cancer

In the treatment group; symptoms of fatigue, anorexia, and nausea and vomiting were lower versus the control group. Also, the occurrence of leukopenia and thrombocytopenia in the treatment group was lower than that of the control group.

Shenqi Fuzheng injection plus chemotherapy for advanced lung cancer can reduce drug toxicity, improve the patient”s fatigue, loss of appetite, gastrointestinal symptoms and improve the quality of life of patients (Jiang, 2012).

Lung Cancer; Chemotherapy

Seventy four lung cancer patients diagnosed on their initial visit were chosen, and randomly divided into 3 groups: chemotherapy alone group (control group) of 21 cases, Shenqifuzheng injection combined with chemotherapy (single drug treatment) group of 25 cases, and Shenqifuzheng injection combined with Bozhi glycopeptide and chemotherapy (combined treatment) group of 28 cases.

The difference in short-term  effect, Karnofsky score, and clinical symptoms among the three groups had statistical significance (P < 0.05). The CD4, CDs, CD4/CD8, NK in peripheral blood lymphocytes, and percentage of natural killer cells were decreased significantly after chemotherapy in the control group; while the same indexes in the treatment group with Shenqifuzheng injection and Bozhi glycopeptide and chemotherapy improved significantly (P < 0.05).

Shenqifuzheng injection combined with Bozhi glycopeptide and chemotherapy can relieve adverse reactions in treating aged lung cancer patients. The combined treatment could also enhance the quality of life, immune function, and reduce complications, and thus is worthy of application in clinical settings (Wang, Zhou, Chang & Shao, 2013).

Gastric Cancer

Rats were injected with different dosages of Shenqi Fuzheng injection (0.04 g/m1, 0.08 g/ml and O. 16 g/ml) for 1 week. Matrigel TM test was performed to detect invasion ability of cells, and RT-PCR was used to check Tn-C mRNA expression.

In treated groups, invasiveness of cells was most significant (the inhibit ratio was 34.7% in 0.16 g/ml group). The expressions of Tenascin-C were lower than those of the control. There was significant difference between the high concentration group and the control.

The expressions of Tenascin-C are down-regulated when gastric cancer MGC-803 cells were treated with Shenqi Fuzheng injection at high concentration, therefore the invasiveness of gastric tumors may be reduced (Ma et al., 2013).

Fifty-three patients with advanced gastric cancer were randomly divided into a treatment group (26 cases) or a control group (27 cases). The treatment group received S-1/cisplatin (SP) chemotherapy plus Shenqi-Fuzheng injection, while the control group was treated with SP chemotherapy only. After 2 cycles of chemotherapy, the efficacy, cellular immune function index, and adverse reactions were observed.

Shenqi-Fuzheng injection plus SP chemotherapy can improve cellular immune function, tolerance to chemotherapy, and reduce toxicity in patients with advanced gastric cancer (Yin & Jiang, 2013).

References

Dong, J., Su, S-Y., Wang, M-Y., Zhan, Z. (2010). Shenqi fuzheng, an injection concocted from chinese medicinal herbs, combined with platinum-based chemotherapy for advanced non-small-cell lung cancer: a systematic review. J Exp Clin Cancer Res, 29(1):137. doi:  10.1186/1756-9966-29-137


Jiang, H. (2012). Clinical observation of the Shenqi Fuzheng injection on the response to chemotherapy in advanced lung cancer patients. Zhong Yi Lin Chuang Yan Jiu, 4(14), 11-12.


Ma, J.W., Song, Y.C., Zhang, Y., Jia, Y., Dang, C.X., & Hou, J. (2013). Effects of Shenqi Fuzheng injection on the invasiveness of cells and expression of Tenascin-C in human gastric cancer MGC- 803 cells. Journal of Modern Oncology, 21(2), 263-266.


Qiao, S. (2012). Effect of Shenqi Fuzheng injection combined with chemotherapy in treatment of advanced non small cell lung cancer clinical observation. Chinese Journal of Practical Medicine, 7(34), 25-26.


Wang, D.H., Zhou, L.H., Chang, C., & Shao, N. (2013). Observation of clinical effects of Shenqifuzheng injection combined with Bozhi glycopeptide and chemotherapy in treating aged lung cancer patients. Medical Review, 19(4), 733-735.


Yin, L.L., & Jiang, C.Y. (2013). Observation on the influence of Shenqi-Fuzheng injection on T-lymphocyte subsets, NKcell and the leukocyte of the patients with advanced gastric cancer. International Journal of Traditional Chinese Medicine, 35(1), 22-24.

anti-proliferative, Chapter 8 Injectables and Cancer Research, Chemotherapy, chemotherapy support, Fatigue, Immune, immunomodulary, Lymphoma, Nausea and Vomiting, Radio-sensitizer, radiotherapy, Weight Gain or Weight Loss

Kangai Injection

Cancers: Cervical., lung, non-Hodgkin”s lymphoma, stomach

Action: Anti-proliferative, chemotherapy support, immunomodulary, radio-sensitizer

Non-Hodgkin’s Lymphoma

The influence of Kangai injection on blood serum vascular endothelial growth factor of non-Hodgkin”s lymphoma patients, and its synergistic effect, attenuation and improvement of quality of life was evaluated.

Eighty-five non-Hodgkin”s lymphoma patients were randomized into a treatment group or control group. The patients in the treatment group were treated by Kangai injection and cyclophosphamide / doxorubicin / vincristine / prednisolone (CHOP) combined chemotherapy, while those in the control group were treated by CHOP chemotherapy only.

The concentration of vascular endothelial growth factor in blood serum of the patients of the treatment group decreased after therapy (P < 0.05), acute curative effect gradually increased, quality of life was raised significantly (P < 0.05), and adverse reactions of the combined chemotherapy decreased markedly (P < 0.05).

Kangai injection, with CHOP chemotherapy, has a synergistic effect. It can attenuate progression of non-Hodgkin”s lymphoma, and improve quality of life. Additionally, it can decrease the concentration of serum vascular endothelial growth (Tang, 2006).

Stomach Cancer; Chemotherapy

Eighty patients with advanced stomach cancer were randomly divided into treatment group (chemotherapy+ GAMA injection) and control group (chemotherapy only). Observation was conducted on cellular immunization, short-termeffect, quality of life improvement, and toxic side-effects in both groups.

In the treatment group, both NK cellular activity and CD4/CD8 ratios were higher after the treatment (P < 0.01). CD3 and CD4 were both increased (P < 0.05). In the control group, the NK cellular activity, CD3, CD4, CD4/CD8 ratio were all lower after the treatment (P < 0.05). The short-term  efficacy rate was 45% in the treatment group and 40% in the control group. The difference was not significant. The treatment group was apparently lower than the control group in leukopenia, nausea and/or vomiting, and peripheral nerve toxicity (P < 0.05). Compared with the control group, less fatigue, better appetite, and Karnofsky score increases were observed in the treatment group (P < 0.01). The treatment group was also more effective in relieving pain and promoting weight gain than the control group (P < 0.05).

Treating advanced stomach cancer, with the combination of Kangai injection and chemotherapy, may decrease the adverse effects of chemotherapy on patients′cellular immune functions and other side effects, and thereby, improve the quality of life of patients (Wu & Yang, 2007).

NSCLC; Chemotherapy

Seventy eight patients with stage IIIB/IV NSCLC were randomly divided into two groups: treatment group (n=40) received GAMA injection and chemotherapy, and control group (n=38) only received chemotherapy.

The short-termeffect, Karnofsky scores of life quality, and the incidence of pancytopenia in treatment group were superior to those in the control group (72.5% vs 47.4%, P<0.05; 87.5% vs 55.3%, P < 0.01; P < 0.01).

Kangai injection can improve the short-term effect, quality of life, and pancytopenia prevalence in patients with intermediate and advanced-stage NSCLC (Wen, Xie, Xie & Feng, 2006).

Radiotherapy side-effects

One hundred ten cases of patients with malignant tumors wasrandomly divided into the treatment group or the control group. The treatment group was given Kangai injection for 40 days after radiotherapy, while the control group was treated by radiotherapy only.

Tumor growth in the treatment group and the control group were 66.7% and 43.4%, respectively. Karnofsky score improvements were 52.6% and 32.1%, respectively. The incidence of leukopenia was 22.8% and 42.5%, respectively. All differences were significant (P < 0.05). There was no significant difference in levels of lymphocytres between the treatment group before and after therapy (P > 0.05). However, there was significant difference in the control group before and after therapy (P< 0.05).

Kangai injection can improve the curative effect and alleviate the side-effects of radiotherapy on treating malignant tumors (Cao et al., 2005).

Leukemia

Kangai injection combination of fludarabine (Flud), cytosine arabinoside (Ara-C), and granulocyte colony-stimulating factor (G-CSF) (FLAG) in refractory/relapsed acute leukemia (AL) patients was investigated. The remission rate of treatment and total effective rate treatment group were 57.1% (16/28) and 71.4% (21/28), the control group were 52.3% (11/21) and 61.9% (13/21); there were no significant differences in the two groups. Duration of neutrophils less than 0.5 x 10(9)/L in treatment group was (14 +/- 6) day, control group was (23 +/- 3) day, Duration of platelet less than 25 x 10(9)/L in treatment group was (17 +/- 6) day, control group was (31 +/- 2) day, treatment group of III-IV degree of infection was 6.9% (1/28) and control group was 23.8% (5/21) between the two groups were significantly different (P < 0.05). treatment group of III- IV degree of gastrointestinal; toxicity was 10.7% (3/28) and control group was 28. 5% (6/ 21).

Kangai injection plus FLAG regimen could increase the remission rate, shorten the period of bone marrow suppression, significantly reduced the incidence and degree of infection, play an important role in attenuated efficiency (Wan et al., 2011).

References

Cao, H. (2005). Treating 57 cases of malignant tumor by Kangai injection and radiotherapy. Zhejiang Journal of Integrated Traditional Chinese and Western Medicine, 2005(12), R730.5. doi: cnki:sun:zjzh.0.2005-12-005.


Tang, Q. (2006). Influence of Kangai injection on blood serum vascular endothelial growth factor of non-Hodgkin lymphoma patient. Journal of Leukemia & Lymphoma, 15(1).


Wan, Q., Xi, A., Zhang, C., Liu X.(2011) Clinical study of kangai injection plus FLAG regimen for refractory/relapsed acute leukemia. Zhongguo Zhong Yao Za Zhi, 36(22):3207-9.


Wen, J.Y., Xie, Z., Xie, J.R., & Feng, L.P. (2006). Kangai injection mixed with chemotherapy in intermediate and advanced-stage non-small-cell lung cancer. Journal of Guandong Medical College, 24(1), 1005-4057.


Wu, L., & Yang, Y. (2007). A clinical study of treating advanced gastric cancer with the combination of Kangai injection and chemotherapy. Proceeding of Clinical Medicine, 18(7), 1671-8631.

anti-tumor, Breast cancer, Chapter 7 Isolates and Cancer Research, Chemotherapy, cytotoxic, Fatigue, Immune, immunomodular, inflammation, Nausea and Vomiting, Th1, TNF

LCS101

Cancer: Breast

Action: Chemotherapy, immunomodular

Breast Cancer

Samuels, Maimon, and Zisk-Rony, (2013) treated a series of 20 female breast cancer patients with the botanical compound LCS101 as adjuvant to conventional chemotherapy. At the end of the treatment regimen, patients rated their symptoms. Seventy percent reported that they had either no or mildly severe levels of fatigue; 60% none to mildly severe weakness; 85% none to mildly severe pain; 70% none to mildly severe nausea; and 80% none to mildly severe vomiting. Only 20% reported severe impairment of overall function, and only 40% severely impaired QOL. No toxic effects were attributed by patients to the LCS101 treatment, and 85% reported that they believed the botanical compound had helped reduce symptoms.

Immunomodular

NK cells are considered to be a central mediator in the 'cross talk' between the adaptive and the innate immune systems, and play an important role in the inhibition and killing of tumor cells (Lee & Gasser, 2010). The LCS101 component Astragalus membranaceus has been shown to stimulate NK-cell activity in human peripheral lymphocytes, as well as restoring steroid-inhibited NK-cell activity (Mills & Bone, 2000). Polysaccharides of this herb were shown to enhance NK cell activity of normal subjects and patients with systemic lupus erythematosus. LCS101 was also shown to enhance cytokine production, increasing TNF-α secretion from murine macrophages 100-fold when compared to untreated controls. TNF-α is a potent anti-tumor cytokine that enhances the activity of macrophages, NK cells, and cytotoxic T cells.

Finally, LCS101 was observed to increase production of IFN-γ, correcting decreased levels following 5-FU treatment, and increasing unaltered levels of the cytokine following exposure to doxorubicin. IFN-γ production is induced by T cells, NK cells, and macrophages, and plays a role in the inhibition of tumor growth, promotion of Th1 immune responses, and differentiation of cytotoxic NK and T cells. Immune-competent mice who lack IFN-γ fail to normalize tissue homeostasis and clear low-level microbial infections, resulting in chronic inflammation with an increased incidence of hematological and solid-tissue cancers (Rachmut et al., 2013).

Induced Hematological Toxicities

Sixty-five breast cancer patients were recruited, with 34 allocated to LCS101 and 31 allocated to placebo treatment. Patients in the treatment group developed significantly less severe (grades 2-4) anemia (p < .01) and leukopenia (p < .03) when comparing grades 0-1 with grades 2-4, with significantly less neutropenia (p < .04) when comparing grades 0-2 with grades 3-4. This effect was more significant among patients undergoing a dose-dense regimen. The addition of LCS101 to anthracycline- and taxane-based chemotherapy is safe and well-tolerated, and may significantly prevent some chemotherapy-induced hematological toxicities in early breast cancer patients (Yaal-Hahoshen et al., 2011).

LCS101 Formula:

Astragalus membranaceus, Poriae cocos, Atractylodes macrocephala, Lycium chinense, Ligustrum lucidum, Paeonia lactiflora, Paeonia obovata, Citrus reticulata, Ophiopogon japonicus, Milletia reticulata, Oldenlandia diffusa, Scutellaria barbata, Prunella vulgaris, and Glehnia littoralis.

References

Rachmut IH, Samuels N, Melnick SJ, et al. (2013). Immunomodulatory effects of the botanical compound LCS101: implications for cancer treatment. Onco Targets Ther, 6:437–445. doi:10.2147/OTT.S42038.


Samuels N, Maimon Y, Zisk-Rony RY. (2013). Effect of the Botanical Compound LCS101 on Chemotherapy-Induced Symptoms in Patients with Breast Cancer: A Case Series Report. Integr Med Insights, 8:1–8. doi: 10.4137/IMI.S10841.


Yaal-Hahoshen N, Maimon Y, Siegelmann-Danieli N, et al. (2011). A prospective, controlled study of the botanical compound mixture LCS101 for chemotherapy-induced hematological complications in breast cancer. Oncologist, 16(9):1197-202. doi: 10.1634/theoncologist.2011-0150.

A549, Akt, Anti-cancer, apoptosis, Apoptotic, Breast cancer, brown seaweed, c-Myc, Chapter 7 Isolates and Cancer Research, Chemoprevention, Chemotherapy, Chemotherapy protective, Colon Cancer or Colorectal cancer, ERK, ERK1, Fatigue, G1, HCT-15, HS-Sultan, Lymphoma, MAPK, p38, PI3K, Prostate cancer, Rectal cancer, ROS, SMMC-7721

Fucoidan

Cancer:
Lymphoma, prostate, hepatocellular carcinoma, breast, colorectal

Action: Chemotherapy protective

Fucoidan is a ulphated polysaccharide found in brown seaweed, including Sargassum thunbergii [(Mertens ex Roth) Kuntze] and Fucus vesiculosus (L.).

Lymphoma

Fucoidan, a sulfated polysaccharide in brown seaweed, was found to inhibit proliferation and induce apoptosis in human lymphoma HS-Sultan cell lines. Fucoidan-induced apoptosis was accompanied by the activation of caspase-3 and was partially prevented by pre-treatment with a pan-caspase inhibitor, z-VAD-FMK. The neutralizing antibody, Dreg56, against human l-selectin, did not prevent the inhibitory effect of fucoidan on the proliferation of IM9 and MOLT4 cells, both of which express l-selectin; thus it is possible fucoidan induced apoptosis through different receptors. These results demonstrate that fucoidan has direct anti-cancer effects on human HS-Sultan cells through caspase and ERK pathways (Aisa et al., 2005).

Colorectal Cancer; Chemotherapy

A total of 20 patients with unresectable advanced or recurrent colorectal cancer scheduled to undergo treatment with FOLFOX or FOLFIRI were randomly allocated into a fucoidan treatment group (n=10) and a control group without fucoidan treatment (n=10). Results showed that fucoidan regulated the occurrence of fatigue during chemotherapy. Chemotherapy with fucoidan was continued for a longer period than chemotherapy without fucoidan. Additionally, the survival of patients with fucoidan treatment was longer than that of patients without fucoidan, although the difference was not significant.

Thus, fucoidan may enable the continuous administration of chemotherapeutic drugs for patients with unresectable advanced or recurrent colorectal cancer, and as a result, the prognosis of such patients is prolonged (Ikeguchi et al., 2011).

Prostate Cancer

Fucoidan obtained from Undaria pinnatifida induced the apoptosis of PC-3 cells by activating both intrinsic and extrinsic pathways. The induction of apoptosis was accompanied by the activation of extracellular signal-regulated kinase mitogen-activated protein kinase (ERK1/2 MAPK) and the inactivation of p38 MAPK and phosphatidylinositol 3-kinase (PI3K)/Akt. In addition, fucoidan also induced the up-regulation of p21Cip1/Waf and down-regulation of E2F-1 cell-cycle-related proteins. Furthermore, in the Wnt/β-catenin pathway, fucoidan activated GSK-3β that resulted in the decrease of β-catenin level, followed by the decrease of c-myc and cyclin D1 expressions, target genes of β-catenin in PC-3 cells. The data support that fucoidan might have potential for the treatment of prostate cancer (Boo et al., 2013).

Hepatocellular Carcinoma

Fucoidan isolated from U. pinnatifida induced apoptosis in human hepatocellular carcinoma SMMC-7721 cells via the ROS-mediated mitochondrial pathway. SMMC-7721 cells exposed to fucoidan displayed growth inhibition and several typical features of apoptotic cells, such as chromatin condensation and marginalization, and a decrease in the number of mitochondria, and in mitochondrial swelling and vacuolation (Yang et al., 2013).

Breast Cancer

Fucoidan exerts its anti-cancer activity through down-regulation of Wnt/β-catenin signaling. Fucoidan may be an effective therapy for the chemoprevention and treatment of mouse breast cancer. Fucoidan significantly inhibited cell growth, increased cell death, and induced G1 cell- cycle arrest in breast cancer 4T1 cells. Fucoidan also reduced β-catenin expression and T cell factor/lymphoid-enhancing factor reporter activity. Furthermore, fucoidan down-regulated the expression of downstream target genes such as c-myc, cyclin D1, and survivin (Xue et al., 2013).

References

Aisa Y, Miyakawa Y, Nakazato T, Shibata H, et al. (2005). Fucoidan induces apoptosis of human HS-Sultan cells accompanied by activation of caspase-3 and down-regulation of ERK Pathways. Am. J. Hematol, 78:7–14. doi: 10.1002/ajh.20182.


Boo HJ, Hong JY, Kim SC, et al. (2013). The anti-cancer effect of fucoidan in PC-3 prostate cancer cells. Mar Drugs, 11(8):2982-99. doi: 10.3390/md11082982.


Ikeguchi M, Yamamoto M, Arai Y, et al. (2011). Fucoidan reduces the toxicities of chemotherapy for patients with unresectable advanced or recurrent colorectal cancer. Oncology Letters, 2(2). doi: 10.3892/ol.2011.254.


Xue M, Ge Y, Zhang J, et al. (2013). Fucoidan inhibited 4T1 mouse breast cancer cell growth in vivo and in vitro via down-regulation of Wnt/β -catenin signaling. Nutr Cancer, 65(3):460-8. doi: 10.1080/01635581.2013.757628.


Yang L, Wang P, Wang H, et al. (2013). Fucoidan derived from Undaria pinnatifida induces apoptosis in human hepatocellular carcinoma SMMC-7721 cells via the ROS-mediated mitochondrial pathway. Mar Drugs, 11(6):1961-76. doi: 10.3390/md11061961.