Integrative Cancer Therapies

Objective. The major aim of this study was to present 2 cancer cases treated with anticancer herbal formula Panax notoginseng and Cordyceps militaris. Methods. Two patients, with pancreatic adenocarcinoma and mucosa-associated lymphatic tissue type lymphoma, respectively, were treated with P notoginseng and C militaris herbal formula without conventional treatments. Their tumor masses were compared using computed tomography during early and later periods of herbal formula treatment. Results. On computed tomography, reduction in tumor mass in both patients after 17 and 13 months of herbal treatments was noted, and the patients maintained stable disease and good quality of life until the last contact in November 2008. Conclusion. C militaris and P notoginseng are potential anticancer herbal prescriptions for adenocarcinoma and mucosa-associated lymphatic tissue type lymphoma.

Purpose. Hepatocellular carcinoma (HCC) is a common malignancy worldwide and has an annual occurrence of one million new cases. Novel therapeutic strategies of increased efficacy in the treatment of HCC-bearing patients would certainly be helpful. Hence, the authors explored the effect of combination treatment of roscovitine with chemotherapeutic drugs or quercetin (Qctn) in hepatoma cells, HepG2 and Hep3B. Methods. Cell viability was assessed by MTT assay, cell growth assay, and nuclear morphological changes by DAPI staining. The altered expression of signaling proteins and apoptotic molecules was established by Western blotting. Results. Roscovitine pretreatment considerably enhanced the drugs and Qctn-induced cell death in HepG2 and Hep3B cells. The exploratory studies revealed that augmented cell killing in HepG2 and Hep3B was mediated via Akt pathway and was independent of p53. pAkt was found to be significantly downregulated in combination treatment of roscovitine with carboplatin or Qctn. Corresponding to reduced expression of pAkt, the downstream molecules Bcl-2 and proactive forms of caspase 9 and caspase 3 were also downregulated indicating apoptosis. Conclusions. The present study reports for the first time, in hepatoma cells, the potentiation of carboplatin- and Qctn-induced cell death by the cell cycle inhibitor roscovitine. Roscovitine can thus be considered as a potential therapeutic target in combination with chemotherapeutic drugs or Qctn for treatment of HCC.

Objectives: To assess feasibility of methods for a future study of complementary and alternative medicine (CAM) use by cancer patients treated in conventional health care settings. Methods: Patients aged 18 years and older, fluent in English or French, and diagnosed with cancer from St. Mary’s Hospital Center, Montreal, Canada participated. Feasibility was measured by the rates of participation and CAM use in the past 1 and 12 months. Following the survey, one patient focus group was held to better understand cancer patient perspectives on discussions of CAM that occur or not with their family physicians. Results: Of 103 patients approached, 100 (97.1%; 77% female, 87% white) participated. Overall, 86% and 91% of respondents used at least one CAM in the past 1 and 12 months, respectively. More patients with breast compared with colorectal and other cancers (90.2%, 86.2%, and 80%, respectively) used CAM in the previous year. In the past 1 and 12 months, natural health products were used by 70% and 80% of respondents, respectively; mind–body therapies by 61% and 64%, respectively, and CAM practitioners by 11% and 29%, respectively. More than 98% of patients used CAM to improve quality of life and 68% disclosed CAM use to their physicians. Four of 5 focus group participants used CAM. Patient–physician CAM discussions varied from receiving a CAM referral to complete dismissal of the topic. Conclusion: Recruitment methods were well accepted but a sampling strategy stratified by sex and ethnicity will ensure sufficient representation by males and non-whites. Whereas disclosure of natural health products use is occurring, informative CAM discussion is not.

Anthracyclines are potent antineoplastic agents associated with cardiotoxicity, which may lead to congestive heart failure, causing impairment of autonomic cardiovascular function as assessed by heart rate variability (HRV). This decreases survival rates. This study aimed to determine whether music therapy intervention improves autonomic function in anthracycline-treated breast cancer patients, and if so, whether such improvements persist after cessation of the intervention. Participants were 12 women with breast cancer who had undergone mastectomy or breast-conserving treatment and adjuvant chemotherapy; they attended 8 weekly music therapy sessions, each lasting 2 hours. Electrocardiogram traces (5 minutes) for HRV analysis were recorded 4 times: prior to the first music session, T1; after the fourth music session, T2; after the eighth music session, T3; and 4 weeks after the completion of music therapy, T4. HRV parameters were subjected to a nonparametric Friedman test on the differences between T1 and T2, T3, and T4. The standard deviation of normal intervals and the total power of HRV parameters, related to global autonomic function, were significantly higher at T3 than at T1. The root-mean-square differences of successive normal R–R intervals and high-frequency (HF) HRV parameters, related to parasympathetic activity, were significantly increased, but no change was seen in the LF/HF ratio of HRV parameters (which is related to sympathetic activity) during the music therapy. Global autonomic function and parasympathetic activity had not changed significantly at T4 relative to T1. The authors provide preliminary evidence of the benefits of music therapy for anthracycline-treated breast cancer survivors.

Background: Taiwan National Health Insurance (NHI) provides Western medicine and Chinese medicine (CM). This study aims to explore the trends of CM use among prostate cancer patients under NHI. Methods: Claims of CM outpatient services from 1996 to 2008 were obtained from NHI Research Database. CM visits of prostate cancer patients were identified. Claims with diagnosis code of prostate cancer were defined as cancer-specific visits. Results: Among 78 323 prostate cancer patients identified during 1996-2008, there were 30 383 (38.8%) CM users and 327 063 CM outpatient visits. The prevalence of CM use in each cross-sectional year increased slightly from 24.9% to 25.6%. Most CM visits (92.7%) were non-cancer-specific. There were greater increases in the proportion of cancer-specific CM visits (from 2.3% to 10.6%) and high-utility CM users (from 3.1% to 19.7%). Most CM services were provided by private clinics (68.1% to 79.2%). The most frequently used CM therapies were Chinese herbal medicine (72.8% to 78.8%), followed by acupuncture/traumatology manipulative therapies (28.1% to 36.8%). Total CM cost increased from $122 247 to $825 454. The average cost per CM visit increased from $14.0 to $19.6. The annual cost per CM user increased from $88.0 to $134.4. Copayment accounted for 6.6% to 11.7%. Conclusions: There was a trend of increased CM use among prostate cancer patients under NHI. Although prostate cancer patients used CM mostly for noncancer diseases, CM visits for prostate cancer increased remarkably. The utilization patterns of CM visits for cancer and for noncancer diseases were distinctly different.

Melanoma is an aggressive tumor that expresses the pigmentation enzyme tyrosinase. Tyrosinase expression increases during tumorigenesis, which could allow for selective treatment of this tumor type by strategies that use tyrosinase activity. Approaches targeting tyrosinase would involve gene transcription or signal transduction pathways mediated by p53 in a direct or indirect manner. Two pathways are proposed for exploiting tyrosinase expression: (a) a p53-dependent pathway leading to apoptosis or arrest and (b) a reactive oxygen species–mediated induction of endoplasmic reticulum stress in p53 mutant tumors. Both strategies could use tyrosinase-mediated activation of quercetin, a dietary polyphenol that induces the expression of p53 and modulates reactive oxygen species. In addition to antitumor signaling properties, activation of quercetin could complement conventional cancer therapy by the induction of phase II detoxification enzymes resulting in p53 stabilization and transduction of its downstream targets. In conclusion, recent advances in tyrosinase enzymology, prodrug chemistry, and modern chemotherapeutics present an intriguing and selective multitherapy targeting system where dietary bioflavonoids could be used to complement conventional cancer treatments.

This study reports the antimigration, anti-invasive effect of glabridin, a flavonoid obtained from licorice, in human non–small cell lung cancer A549 cells. Glabridin exhibited effective inhibition of cell metastasis by decreasing cancer cell migration and invasion of A549 cells. In addition, glabridin also decreased A549-mediated angiogenesis. Further investigation revealed that glabridin’s inhibition of cancer angiogenesis was also evident in a nude mice model. Blockade of A549 cells migration was associated with an increase of ανβ3 integrin proteosome degradation. Glabridin also decreased the active forms of FAK and Src, and enhanced levels of inactivated phosphorylated Src (Tyr 527), decreasing the interaction of FAK and Src. Inhibition of the FAK/Src complex by glabridin also blocked Akt activation, resulting in reduced activation of RhoA and myosin light chain phosphorylation. This study demonstrates that glabridin may be a novel anticancer agent for the treatment of lung cancer in 3 different ways: inhibition of migration, invasion, and angiogenesis.

Isolinderanolide B (IOB), a butanolide extracted from the stems of Cinnamomum subavenium, was investigated for its antiproliferative activity in T24 human bladder cancer cells. To identity the anticancer mechanism of IOB, its effect on apoptosis, cell cycle distribution, and levels of p53, p21 Waf1/Cip1, Fas/APO-1 receptor, and Fas ligand was assayed. Enzyme-linked immunosorbent assay showed that the G0/G1 phase arrest is because of increase in the expression of p21 Waf1/Cip1. An enhancement in Fas/APO-1 and membrane-bound Fas ligand (mFasL) might be responsible for the apoptotic effect induced by IOB. This study reports the novel finding that the induction of p21 Waf1/Cip1 and activity of the Fas/mFas ligand apoptotic system may participate in the antiproliferative activity of IOB in T24 cells.

Background and objective: The extracts of Cordyceps sinensis (Berk) Sacc (CS) have been used as a traditional medicine for centuries. However, few studies have examined the adjuvant action of CS in the treatment of non–small cell lung cancer (NSCLC). So the aim of this study is to investigate the adjuvant role of CS in the treatment of NSCLC. Methodology: The effects of the combination treatment of the polysaccharide-rich fraction of CS and cisplatin on H157 NSCLC cells were investigated through MTT assay for cell viability, lactate dehydrogenase and fluorescein diacetate and propidium iodide assay for cytotoxicity, and with flow cytometric analysis for apoptosis. The expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in H157 cells were detected by immunohistochemistry. Results: Compared with the cells treated with cisplatin alone, cell viability was significantly decreased and the expression levels of VEGF and bFGF protein were significantly reduced in the cells treated with a combination of CS and cisplatin. Conclusion: The current study indicates that the polysaccharide of CS inhibits tumor growth in NSCLC and that CS may be a potential adjuvant chemotherapeutic agent in NSCLC therapy.

Laser immunotherapy (LI) has been demonstrated to be a promising modality for cancer treatment. The present study was designed to further investigate the impact of LI combined with surgery. LI consists of a near-infrared laser, a light-absorbing dye (indocyanine green, ICG), and an immunostimulant (glycated chitosan, GC). ICG and GC were intratumorally injected, followed by laser irradiation. Female BALB/c mice bearing EMT6 tumor cells were divided into 4 groups: control, LI, LI followed by immediate surgery resection of residual tumor (LI + S_0wk), and LI followed by surgical removal of residual tumor after 1 week (LI + S_1wk). Successfully treated mice from all treatment groups were rechallenged twice with 10⁵ and 5 × 10⁵ EMT6 cells, respectively. The LI + S_1wk group had the highest survival rate (72%) after 90 days, whereas the mice survival rates of the LI + S_0wk, LI, and control groups were 50%, 46%, 0%, respectively. The median survival times of control, LI, LI + S_0wk, and LI + S_1wk groups were 32, 66, 74, and 90 days, respectively. Survival rates of the treated mice after the first and second tumor rechallenges, ranging from 73% to 95%, were not significantly different among the 4 groups (P > .05). The results show that LI is a useful tool for the treatment of tumor-bearing mice. Long-term antitumor effect can be induced by LI. They also indicate that combination of LI with surgery can further improve the therapeutic efficiency of LI.

The radioprotective effect of thymol (TOH), a monoterpene phenol, on radiation-induced DNA damage was analyzed in vitro. Chinese hamster lung fibroblast cells (V79) were treated with different concentrations of TOH (0-100 µg/mL) for 1 hour before exposure to 3 Gy gamma irradiation, and then cytokinesis-blocked micronucleus and single-cell gel electrophoresis (comet assay) assays were used to evaluate the radiation-induced cytogenetic damage and genotoxic effects. Furthermore, the modulating effect of TOH on radiation-induced cell death was assessed by apoptotic and necrotic cell detection by staining with ethidium bromide/acridine orange using fluorescence microscopy. To understand the mechanism of TOH-imparted cytoprotection, mitochondrial membrane potential (MMP) was detected by flow cytometry after staining the cells with Rhodamine 123. Pretreatment of V79 cells with various concentrations of TOH (0-100 µg/mL) for 1 hour reduced the radiation-induced micronuclei as well as percent tail DNA and mean Olive tail moment with a maximum protective effect observed at TOH (25 µg/mL). Apoptosis by microscopic, MMP measurements indicated that the V79 cells exposed to gamma radiation alone showed a maximal increase in the number of early and late apoptotic and necrotic cell death associated with a significant loss of the MMP. Pretreatment with TOH (25 µg/mL) showed a significant (P < .01) decrease in the level of apoptotic fraction as well as necrotic cells and suppressed the radiation-induced collapse of MMP when compared with the radiation alone group. These results suggest that TOH suppresses radiation-induced genotoxicity, apoptosis, and necrosis primarily by the free radical scavenging and modulation of oxidative stress.