Integrative Cancer Therapies

The essential trace element selenium, which is a crucial cofactor in the most important endogenous antioxidative systems of the human body, is attracting more attention from both laypersons and expert groups. The interest of oncologists mainly focuses on the following clinical aspects: protection of normal tissues, sensitizing in malignant tumors, antiedematous effect, prognostic impact of selenium, and effects in primary and secondary cancer prevention. Selenium is a constituent of the small group of selenocysteine-containing selenoproteins and elicits important structural and enzymatic functions. Selenium deficiency has been linked to increased infection risk and adverse mood states. It has been shown to possess cancer-preventive and cytoprotective activities in both animal models and humans. It is well established that it has a key role in redox regulation and antioxidant function, and hence in membrane integrity, energy metabolism, and protection against DNA damage. Recent clinical trials have shown the importance of selenium in clinical oncology. In 2009, a significant benefit of sodium selenite supplementation—with no protection of tumor cells, which is often suspected by oncologists— was shown in a prospective randomized trial in gynecologic cancer patients undergoing radiation therapy. More recently, concerns arose from 2 large clinical prevention trials (NPC, SELECT) that selenium may increase the risk of developing type 2 diabetes. Despite obvious flaws in both studies and good counterarguments, controversy remains on the possible advantages and risks of selenium in cancer prevention. However, in the light of the recent clinical trials the potential benefits of selenium supplementation in tumor patients are becoming obvious, even though further research is needed.

Background. Acupuncture is underutilized as an adjunct cancer therapy. The main study objectives were to determine the feasibility of administering acupuncture as palliative therapy to patients with advanced ovarian or breast cancer and to assess the effect on symptoms and quality of life (QOL). Methods. This study was a pilot, single-armed prospective clinical trial for patients with advanced cancer to receive 12 acupuncture sessions over 8 weeks with follow-up at weeks 9 and 12. Ambulatory patients with advanced ovarian or breast cancer were enrolled to receive treatments at an outpatient academic oncology center. Symptom severity was measured before and after each acupuncture session. A composite QOL assessment tool, consisting of validated instruments, was completed at 5 time points. Results. Forty patients enrolled in the study. Twenty-eight patients (70%; 95% confidence interval [CI] = 53%-83%) completed 4 weeks of treatment, and 26 patients (65%; 95% CI = 48%-79%) completed 8 weeks. Eight patients (20%) withdrew before receiving acupuncture, and 6 patients (15%) discontinued treatment early because of disease progression or scheduling demands. Among all 32 assessed patients, there was self-reported improvement immediately post-treatment in anxiety, fatigue, pain, and depression and significant improvement over time for patients with anxiety (P = .001) and depression (P = .02). Among patients experiencing baseline symptoms, there was improvement in anxiety (P = .001), fatigue (P = .0002), pain (P = .0002), and depression (P = .003). QOL measures of pain severity and interference, physical and psychological distress, life satisfaction, and mood states showed improved scores during treatment, with sustained benefit at 12 weeks. Conclusions. This pilot study demonstrates that an 8-week outpatient acupuncture course is feasible for advanced cancer patients and produces a measurable benefit that should be evaluated in controlled trials.

Objective. The current study aimed to (1) describe communication patterns between oncologists and breast cancer patients regarding the use of complementary and alternative medicine (CAM) and (2) assess the relationship between CAM discussions and anxiety levels. Methods. Interaction analysis of audiotaped initial consultations of 102 early-stage breast cancer patients with Australian and New Zealand oncologists was carried out. Preconsultation and postconsultation anxiety levels were assessed using the State-Trait Anxiety Inventory. Results. At least 1 instance of CAM discussion was found in 24 of the 102 consultations (24%). CAM discussions were mainly patient initiated (73%). The most common doctor’s response to a patient’s mention of CAM was encouragement (38%), although 23% of CAM references elicited a discouraging comment, and 20% were ignored. No patient demographics were significantly associated with CAM discussion. Patients who discussed CAM reported higher preconsultation and postconsultation anxiety levels than those who did not discuss CAM. Conclusions. CAM discussions during initial consultations between early-stage breast cancer patients and oncologists appear to be limited and linked with higher patient anxiety before and after the consultation. These findings indicate that doctors require further education about CAM therapies and supplements as well as guidance in how to raise and effectively discuss CAM issues with concern for their safety while balancing respect for the patients’ beliefs.

In recent years, there has been an increased interest in complementary and alternative medicine (CAM) use among people with cancer. Many are looking for informed advice and desire communication with their physicians about CAM use. Communication is crucial in establishing trust with patients, gathering information, addressing patient emotions, and assisting patients in decisions about care. The quality of communication in cancer care has been shown to affect patient satisfaction, decision making, patient distress and well-being, compliance, and even malpractice litigation. Communication is now recognized as a core clinical skill in medicine, including cancer care, and is important to the delivery of high-quality care. A communication approach that fosters a collaborative relationship that includes adequate information exchange, responds to emotional needs, and manages uncertainty can lead to informed decisions about CAM use. This type of communication can help facilitate an open discussion with cancer patients and their families about integrating CAM use into their care and help physicians fulfill their roles in caring, comforting, and healing, even when cure is not possible. In this article, the authors discuss a possible model of effective patient—physician communication about CAM use in cancer care based on a comprehensive overview of the literature.

The anticancer effects of ProstaCaid, a novel integrative blend of vitamins, minerals, multiherb extracts, and derivatives, were tested in human and mouse androgen—dependent (AD) and —independent (AI) prostate cancer cell lines. ProstaCaid shows growth inhibitory effects on both human and mouse AD prostate cancer cells (LNCaP and CASP 2.1) and AI prostate cancer cells (PC3 and CASP 1.1) in a dose-/time-dependent manner. Consistently, long-term treatment with ProstaCaid also reduced colony formation capacities of prostate cancer cells. Flow cytometry assays revealed that ProstaCaid induces G2/M arrest and apoptosis in LNCaP and PC3 cells after 72 hours of treatment. Immunoblotting assay demonstrated that 25 µg/mL of ProstaCaid treatment resulted in (1) the reduction of cyclin D1, cyclin B1, and Cdc2 expression in a time-dependent way; (2) increase in p21^WAF1/Cip1 as early as 12 hours after the treatments in PC3 cells and reduction to base line at the 72-hour time point; and (3) repression of Bcl-2, BclxL, and induction of Bim as well as the cleavages of caspase-3 and poly(ADP-ribose) polymerase (PARP) at 72 hours of treatment, suggesting caspase-3-dependent apoptosis. Moreover, ProstaCaid suppressed activation of AKT and MAPK signaling pathways in PC3 and LNCaP cells by reducing phosphorylation levels of AKT, its downstream target S6 ribosomal protein and GSK3β, and ERK1/2, respectively. In summary, these findings strongly suggest that ProstaCaid may be a potential chemopreventive and therapeutic agent for both AD and, more importantly, AI prostate cancer.

Aim: To demonstrate the efficacy of PectaSol-C modified citrus pectin (MCP) on prostate cancer in vitro. Method: Cytotoxicity analysis of PectaSol-C was performed by MTT assay, as were parallel studies with the former brand version of MCP called PectaSol. Apoptosis and inhibition of cell growth were investigated by Western blotting. Results: Androgen-dependent and -independent human prostate cancer cell lines (LNCaP and PC3, respectively), androgen-dependent and -independent murine prostate cancer cell lines (CASP2.1 and CASP1.1, respectively), as well as noncancerous human benign prostate hyperplasia BPH-1 cell line, were used in the study. MTT assay revealed that 1.0% PectaSol exerted cytotoxicity on LNCaP, PC3, CASP2.1, CASP1.1, and BPH-1 cells for 4-day treatment by 48.0% ± 2.1%, 54.4% ± 0.3%, 15.4% ± 0.8%, 46.1% ± 1.7%, and 27.4% ± 1.6%, respectively; whereas 1.0% PectaSol-C showed cytotoxity by 52.2% ± 1.8%, 48.2% ± 2.9%, 23.0% ± 2.6%, 49.0% ± 1.3%, and 26.8% ± 2.6%, respectively. Western blotting further confirmed that both MCPs inhibit MAP kinase activation, increase the expression level of its downstream target Bim, a pro-apoptotic protein, and induce the cleavage of Caspase-3 in PC3 and CASP1.1 prostate cancer cells. Conclusion: PectaSol MCP and PectaSol-C MCP can inhibit cell proliferation and apoptosis in prostate cancer cell lines. Our data suggested that 1.0% PectaSol-C can be used for further chemopreventive and chemotherapeutic analysis in vivo.

The traditional Chinese medicine, Hong-Qu, also called red mold rice in the United States and Europe, is used for treating blood stasis, a disorder related to hyperlipidemia and atherosclerosis. In addition to improving metabolic syndrome, extracts from Monascus-fermented rice inhibit the proliferation of various cancer cells in vitro and in vivo. The objective was to examine the effect of red mold rice ethanol extract (RMRE) on angiogenesis, invasion, and metastasis during tumor progression. RMRE significantly inhibited the proliferation of SW480 and SW620 human colorectal carcinoma cells in a dose- and time-dependent manner by using the MTT assay. A capillary-like network morphology was observed after the addition of 20 ng/mL vascular endothelial growth factor or SW620 culture-conditional medium, which was not seen after RMRE treatment. Moreover, spontaneous intravasation into Matrigel grafts of SW620 cells from the upper to the lower layers in the chick embryo chorioallantoic membrane (CAM) model was detected by the polymerase chain reaction (PCR) amplification of human Alu genomic DNA from the lower CAMs in the RMRE-untreated group. Neovascularization increased to 75.3% ± 11.6% by SW620 cells onplant with Matrigel grafts in the CAM model. However, RMRE significantly reduced CAM neovascularization in a dose-dependent manner. Finally, RMRE effectively decreased the activity of matrix metalloproteinase (MMP)-7 as determined by reverse transcription PCR (RT-PCR), Western blotting, and casein zymography assays. In summary, Monascus-fermented products exert a potent effect on tumor growth and activation, suggesting that they may serve as supplementary agents in adjuvant cancer therapy.

The effect of oxymatrine on the development of tolerance to the antinociceptive effects of morphine was investigated in rats. The degree of tolerance was assessed using the tail-flick test before and after 6 days of twice daily administration of oxymatrine premorphine (10/20/30 mg/kg). High doses of oxymatrine inhibited the development of morphine tolerance (resembling the effect of 7.5 mg/kg of the NMDA receptor antagonist memantine) while also increasing the antinociceptive effects. A high dose of oxymatrine (30 mg/kg) also significantly inhibited the dramatic increase in expression of morphine-induced P-glycoprotein (P-gp), an ATP-dependent efflux pump acting at the blood—brain barrier, by Western blot analysis. Furthermore, these studies suggest that P-gp modulates the development of morphine tolerance while not affecting the magnitude of the analgesic effect of morphine. These results imply that oxymatrine prevention of the development of tolerance of morphine may be related to a considerable inhibition of P-gp expression. In contrast, the authors’ data suggest that the mechanism of oxymatrine enhancement of morphine’s analgesic effects is not associated with increase in the level of expression of P-gp. However, they believe that their findings can be used by researchers to develop therapies that will allow patients to take morphine without becoming tolerant of its benefits.

The preventive effective of Zataria multiflora (ZM) extract was investigated in mouse bone marrow cells against genotoxicity induced by cyclophosphamide (CP). Mice were orally (gavaged) pretreated with solutions of ZM extract prepared at 3 different doses (50, 100, and 200 mg/kg body weight) for 7 consecutive days. They were injected with CP (50 mg/kg body weight) on the seventh day of treatment and killed after 24 hours for the evaluation of micronucleated polychromatic erythrocytes (MnPCEs) and the ratio of PCE/(PCE + NCE), where PCE refers to polychromatic erythrocyte, and NCE refers to normochromatic erythrocyte. All 3 doses of extract significantly reduced MnPCEs induced by CP (P < .0001). Zataria extract at a dose of 200 mg/kg body weight reduced MnPCEs 7.8 fold and also completely normalized the PCE/ (PCE + NCE) ratio. Administration of ZM inhibited bone marrow suppression induced by CP. Zataria extract exhibited concentration-dependent antioxidant activity on 1, 1-diphenyl 2-picryl hydrazyl free radical and lipid peroxidation. It appeared that ZM with antioxidative activity reduced the oxidative stress and genotoxicity induced by CP in mouse bone marrow cells.

Angiogenesis, the formation of new capillaries from preexisting vessels, is essential for tumor progression. Ursolic acid inhibited the tumor-associated capillary formation in C57BL/6 mice induced by highly metastatic B16F-10 melanoma cells. The levels of serum vascular endothelial growth factor (VEGF), NO, and proinflammatory cytokines were significantly reduced in ursolic acid—treated animals compared with those in control animals. The diminished expressions of VEGF and iNOS genes in B16F-10 melanoma cells treated with nontoxic concentrations of ursolic acid support these observations; the serum TIMP-1 (tissue inhibitor of metalloproteinase-1) and IL-2 (interleukin-2) levels were significantly elevated after the ursolic acid treatment. Nontoxic concentrations of ursolic acid toward human umbilical vein endothelial cells (HUVEC) were determined by MTT (methylthiazol tetrazolium) assay, and these nontoxic concentrations were selected for the in vitro studies. Nontoxic concentrations of ursolic acid inhibited vessel growth from the rat aortic ring. ³H-thymidine proliferation assay clearly showed the inhibitory effect of ursolic acid on the proliferation of HUVECs in vitro. Ursolic acid significantly inhibited endothelial cell migration and invasion. The role of metalloproteinases has been shown to be important in angiogenesis; therefore, gelatin zymography was performed to determine whether ursolic acid affected protease activity. Gelatin zymographic analysis showed the inhibitory effect of ursolic acid on the protein expression of matrix metalloproteinases MMP-2 and MMP-9. The above observation shows the antiangiogenic activity of ursolic acid.

Aim. To introduce the application of wheel balance cancer therapy (WBCT) in cancer treatment through an intensive study of a representative patient. Method. A 59-year-old, female patient who was a secondhand smoker and who carried no significant medical and family history was diagnosed with T1N0M1 (stage 4) lung adenocarcinoma. Immunohistochemistry was positive for thyroid transcription factor-1, CK7, cyclin D1, p53, and Ki-67 on both lung biopsy specimens. An open lobectomy with mediastinal nodal dissection followed. The patient was transferred to East-West Cancer Center (EWCC) suffering from exertional dyspnea (NYHA [New York Heart Association] grade 2) with thoracic pain and pain in both upper limbs because of the decreased ventilatory capacity and reduced exercise capacity after a pulmonary resection. She also complained of emotional stress. EWCC provided WBCT, a multimodality alternative protocol based on the theory of traditional oriental medicine. Physicians regularly monitored whether metastasis or recurrence existed through blood and radiation tests. Observations and dialogues with the patient were used to record the changes in symptoms such as thoracic pain, dyspnea, anxiety, and fear. Results . Treatments at EWCC led to a disease-free survival of 28 months without adjuvant chemotherapy. Neither metastasis nor recurrence occurred during this period. Exertional dyspnea recovered to NYHA grade 1. Other physical and psychological symptoms were alleviated. Conclusion. This report suggests that WBCT may have the potential for extending life expectancy, controlling symptoms, and improving quality of life in cancer patients.

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