Complementary therapies, herbs, and other OTC agents

Graviola demonstrated anticancer effects in vitro, but has not been studied in humans. Despite the lack of human data, many websites promote graviola to cancer patients based on traditional use and on the in vitro studies. Caution is required as there is no evidence of safety or efficacy.     

Liver protective effect of Lentinula edodes mycelia(LEM)

The hot-water extracts of Lentinula edodes mycelia(LEM)contain carbohydrates, proteins, phenolic compounds, and lignin digest, which perform various physiological activities. LEM has hepatoprotective activities in animals with acute liver injury induced by concanavalin A or D-galactosamine.Moreover, LEM suppresses liver fibrosis and inflammation in mice with chronic liver injury induced by carbon tetrachloride. Vanillic acid and syringic acid contained in LEM also showed hepatoprotective activities in mice with acute and chronic liver injury, and low-molecular-weight lignin maintained the viability of primary cultured hepatocytes treated with carbon tetrachloride. LEM containing anti-oxidation and anti-inflammation activities might be used for alleviating side effects of chemotherapy and preventing the progression of liver cancer for patients with chronic hepatitis.     

Complementary therapies and childhood cancer.

BACKGROUND: The use of complementary and alternative therapies by children with cancer is common. Up to 84% of children have used complementary therapies along with conventional medical treatment for cancer. METHODS: We reviewed the PubMed and CINAHL databases for studies published between 1994 and 2004 on the use of complementary and alternative therapies by children with cancer and reports from any publication year through 2004 of clinical trials involving complementary and alternative therapies for children with cancer. RESULTS: Fourteen studies were retrieved reporting the results of survey or interview data collected from parents on children's use of complementary and alternative therapies during or after childhood cancer. Across studies, the use of such therapies ranged from 31% to 84%. Common reasons for using complementary and alternative therapies were to do everything possible for their child, to help with symptom management, and to boost the immune system. Many parents indicated they also hoped to treat or cure the cancer. In most cases, the child's treating physician had not been informed of the child's use of complementary and alternative therapies. CONCLUSIONS: Use of complementary therapies by children with cancer is common, although methodological variations limit the ability to compare results across studies. Treating physicians often do not know the child is using complementary therapies in addition to medical treatments. The scientific evidence is limited regarding the effects and mechanisms of action of complementary or alternative therapies, but research is being conducted on these topics.     

Molecular targeted therapies for cancer: sorafenib mono-therapy and its combination with other therapies (review)

Sorafenib is an oral multikinase inhibitor that acts by inhibiting tumor growth and disrupting tumor microvasculature through antiproliferative, anti-angiogenic and proapoptotic effects. It exerts these effects via inhibition of multiple targets including Raf serine/threonine kinases, vascular endothelial growth factor receptor tyrosine kinases; VEGFR-1, VEGFR-2, VEGFR-3 and platelet-derived growth factor receptor?β (PDGFR-β). Current literature shows that the deregulated signaling through these receptors is commonly seen in human tumors. In addition, sorafenib is also shown to induce apoptosis through downregulation of Mcl-1 in many cancer types. Hence, sorafenib as a single agent has shown promising activity in some cancers such as renal cell carcinoma (RCC), hepatocellular carcinoma (HCC) and thyroid cancers. Currently, the drug holds FDA approval for the treatment of advanced RCC and unresectable HCC. However, many clinical studies have indicated several limitations to the application of sorafenib as a single agent in various other cancers. Owing to these reasons and the potential of sorafenib to synergize with other anticancer therapies, its combination with other targeted agents and chemotherapy has been widely explored with promising results. In addition, it has also shown synergistic results when combined with radiation. This review summarizes the current basic and clinical studies on the effects and mechanisms of sorafenib either administered alone or in combination with other anticancer treatments.     

Selective induction of apoptosis in murine skin carcinoma cells (CH72) by an ethanol extract of Lentinula edodes

The effects of ethanol extracts from four species of mushroom fruiting bodies, mushroom spores and mushroom cultured broth, were assessed for modulation of cell proliferation and apoptosis in murine skin carcinoma cells (CH72) and non-tumorigenic epidermal cells (C50). While extracts from mycelia of Grifola frondosa, Ganoderma lucidum, Hericium erinaceus, or from spores of G. lucidum exerted little, if any, effect on proliferation, the ethanol-soluble extract of Lentinula edodes (L. edodes) significantly decreased cell proliferation of CH72 cells. There were no changes in the proliferative response of the non-tumorigenic keratinocyte cell line, C50, to any of the mushroom extracts tested. To analyze cell proliferation and apoptosis, fluorescent DNA-microscopy with ethidium bromide and acridine orange staining of cells revealed L. edodes reduced cell proliferation and induced apoptosis in time- and dose-dependent manners in carcinoma cells but had no effect in non-tumorigenic cells (C50). Cell cycle analysis demonstrated that L. edodes extract induced a transient G(1) arrest, with no changes observed in the non-tumorigenic cells (C50).     

Potentiation of cytotoxic cancer therapies by TNP-470 alone and with other anti-angiogenic agents

The ability of TNP-470, a synthetic analog of fumagillin which has been described as an anti-angiogenic agent, to potentiate cytotoxic cancer therapies was investigated in vivo in the murine FSaIIC fibrosarcoma and the Lewis lung carcinoma. TNP-470 was more toxic toward FSaIIC tumor cells from tumors treated in vivo than toward bone-marrow CFU-GM from the same animals. TNP-470 had a dose-modifying effect on the toxicity of cyclophosphamide toward FSaIIC tumor cells which amounted to an 8-fold increase in tumor-cell killing at a cyclophosphamide dose of 500 mg/kg. Treatment with TNP-470 and minocycline increased the permeability of the FSaII fibrosarcoma in vivo to the fluorescent dye Hoechst 33342 and increased the killing of both the bright and the dim tumor cells by cyclophosphamide. TNP-470, especially in combination with minocycline, formed a highly effective modulator combination for treatment of the Lewis lung carcinoma with cytotoxic cancer therapies against primary and metastatic disease. The combination of TNP-470/minocycline and cyclophosphamide led to 40 to 50% long-term survivors in Lewis-lung-carcinoma-bearing animals. Our results indicate that the use of anti-angiogenic modulators in cancer therapy is a very promising area for further study. © 1994 Wiley-Liss, Inc.     

Expression and Characterization of Protein Latcripin-3, an Antioxidant and Antitumor Molecule from Lentinula edodes C91-3

In this study, an anti-oxidant and anti-tumor protein Latcripin-3 of Lentinula edodes C91-3 was expressed in Escherichia coli. for the first time. According to the cDNA library, the full-length gene of Latcripin-3 was cloned by the methods of 3’-full rapid amplification of cDNA Ends (RACE) and 5’-full RACE. The structural domain gene of Latcripin-3 was inserted into the pET32 a(+). The functional protein of Latcripin-3 was expressed in Rosetta-gami (DE3) E. coli, evaluated by Western blotting and mass spectrometry. DPPH testing showed that the protein Latcripin-3 can scavenge free radicals remarkably well. The activity of functional protein Latcripin-3 on A549 cells was studied with flow cytometry and the MTT method. The MTT assay results showed that there was a decreases in cell viability in a dose-dependent and time-dependent manner in protein Latcripin-3 treated groups. Flow cytometry demonstrated that Latcripin-3 can induce apoptosis and block S phase dramatically in human A549 lung cancer cells as compared to the control group. At the same time, the cell ultrastructure observed by transmission electron microscopy supported the results of flow cytometry. This research offers new insights and advantages for identifying anti-oxidant and anti-tumor proteins.     

Combination of antiangiogenic therapy with other anticancer therapies: results, challenges, and open questions.

Angiogenesis is necessary for tumor growth. Drug discovery efforts have identified several potential therapeutic targets on endothelial cells and selective inhibitors capable of slowing tumor growth or producing tumor regression by blocking angiogenesis in in vivo tumor models. Certain antiangiogenic therapeutics increase the activity of cytotoxic anticancer treatments in preclinical models. More than 75 antiangiogenic compounds have entered clinical trials. Most of the early clinical testing was conducted in patients with advanced disease resistant to standard therapies. Several phase III trials have been undertaken to compare the efficacy of standard chemotherapy versus the same in combination with an experimental angiogenesis inhibitor. Preliminary results of the clinical studies suggest that single-agent antiangiogenic therapy is poorly active in advanced tumors. Although some of the results of combination trials are controversial, recent positive outcomes with an antivascular endothelial growth factor antibody combined with chemotherapy as front-line therapy of metastatic colorectal cancer have renewed enthusiasm for this therapeutic strategy. This article presents an overview of experimental and clinical studies of combined therapy with antiangiogenic agents and highlights the challenges related to the appropriate strategies for selection of the patients, study design, and choice of proper end points for preclinical and clinical studies using these agents.     

Clinical pharmacology of anticancer agents. (Part 1) Introduction, alkylating agents and platinum compounds

Pharmacokinetic concepts as to absorption, distribution, metabolism and excretion of anticancer agents, and how drugs reach to the site of action were reviewed. Then, roles of the liver and kidney to the excretion and metabolism, intracellular pharmacokinetics, and relationships between drug response and cell proliferation kinetics or cell cycle phase were explained. Drug development, mode of action and pharmacokinetics of alkylating agents and platinum compounds were reviewed. This includes: alkylating agents: nitrogen mustard, phenylalanine mustard, estracyte, cyclophosphamide, carboquone, busulfan, nitrosourea, etc., and platinum compounds: cisplatin, carboplatin, 254-S, DWA-2114 R, NK-121.     

Targeted delivery of biologic and other antineoplastic agents.

This review summarizes several strategies under investigation for targeted delivery of antineoplastic agents to tumor cells, which avoids normal tissue damage. Monoclonal antibodies remain the molecules of choice for targeted therapy, and several improvements to immunotargeting are discussed. These improvements include the use of novel radioisotopes, cytokines, new linkers for chemotherapeutic drugs, more potent drugs, and improved immunotoxins. Bifunctional antibodies, in which one antigen-binding site recognizes a tumor-associated antigen and the other an antineoplastic agent, have been investigated for radioimmunotherapy and for the activation of cytotoxic cells for targeted immunotherapy. The activation of relatively nontoxic prodrugs by antibody-enzyme conjugates is increasingly being investigated in an effort to reduce the systemic toxicity associated with conventional chemotherapy. Finally, the use of liposomes as carriers of drugs or as activators of macrophages is described.     

Anti-tumour and anti-vascular effects of cediranib (AZD2171) alone and in combination with other anti-tumour therapies

Purpose

Cediranib (AZD2171) is a highly potent inhibitor of all three vascular endothelial growth factor receptors. The aim of this preclinical study was to examine the effect of combining cediranib with mechanistically distinct anti-tumour therapies.

Methods

Cediranib (1.5 or 3 mg/kg/day) was evaluated alone and in combination with either gefitinib, imatinib, ZD6126, saracatinib, selumetinib, bevacizumab, 5-fluorouracil (5-FU), docetaxel, oxaliplatin, gemcitabine, pemetrexed, irinotecan or cisplatin in human tumour xenograft models. Anti-tumour activity was measured by assessing the change in tumour volume following treatment compared with vehicle-treated time-matched controls.

Results

In all cases, the combination regimens, at tolerated doses and schedules, inhibited tumour growth to a greater extent than the corresponding monotherapy treatments. Compared with cediranib alone, statistically significant enhancements in anti-tumour activity were observed with all combination regimens. Notably, after 14 days of treatment, the combination of cediranib with ZD6126 induced substantial tumour regression (60 % compared with pre-treatment volume), whilst treatment with each agent alone led only to partial growth inhibition. A combination of cediranib with gefitinib also induced tumour regressions, and cediranib combined with either gemcitabine or irinotecan was found to inhibit tumour growth profoundly (by 99 and 98 %, respectively).

Conclusions

Combining cediranib with selected cytotoxic or targeted agents proved efficacious in a range of human tumour xenograft models.     

Antiangiogenic agents potentiate cytotoxic cancer therapies against primary and metastatic disease.

The formation of a blood supply (angiogenesis) is critical to the growth of solid tumors. The naturally occurring steroid tetrahydrocortisol, the synthetic cyclodextrin derivative beta-cyclodextrin tetradecasulfate, and the tetracycline derivative minocycline have antiangiogenic activity. Tetrahydrocortisol and beta-cyclodextrin tetradecasulfate in a 1:1 molar ratio by continuous infusion over 14 days and minocycline administered i.p. over 14 days from day 4 to day 18 postimplantation of the Lewis lung carcinoma significantly increased the growth delay of the primary tumor after treatment with cis-diamminedichloroplatinum(II), melphalan, cyclophosphamide, Adriamycin, bleomycin, and radiation therapy administered in standard regimens. Addition of the antiangiogenic agents to treatment with the cytotoxic therapies not only reduced the number of lung metastases formed from the primary tumor but also reduced the number of large metastases. Five of 12 animals treated with the antiangiogenic modulators and cyclophosphamide were long-term survivors (> 120 days). Thus, antiangiogenic therapies can potentiate the efficacy of standard anticancer therapies.     

Complementary and Alternative Medicine (CAM) in Uro-Oncology

The West German Comprehensive Cancer Center is confronted with more than 30 000 questions per year concerning unconventional anti-cancer strategies. Unconventional or complementary drugs are not to be compared with placebos. Similar to cytotoxic drugs, unconvetional drugs have to be tested according to the guidelines of (GCP). An adjuvant treatment with unconventional drugs is not indicated. Because an possible immunomodulating effect, long-term results have to be considered - especially related to tumor progression. Right now a routine application of unconventional drugs is not indicated in the field of urological oncology.