Anti‐cachectic Effect of FK317, a Novel Anti‐cancer Agent, in Colon26 and LX‐1 Models in Mice

Takahashi

Evidence-Based Complementary and Alternative Medicine

et al. 2012

Cachexia, a major cause of cancer-related death, is characterized by depletion of muscle and fat tissues, anorexia, asthenia, and hypoglycemia. Recent studies indicate that secretions of proinflammatory cytokines such as interleukin-6 (IL-6) play a crucial role in cachexia development, and that these cytokines are secreted from not only cancer cells but also host cells such as macrophages. In this study, we investigated the therapeutic effects of hochuekkito, a Kampo formula, on cachexia induced by colon 26 adenocarcinoma in mice. Hochuekkito treatment did not inhibit tumor growth, but significantly attenuated the reduction in carcass weight, food and water intake, weight of the gastrocnemius muscle and fat tissue around the testes, and decrease of serum triglyceride level compared with controls. Furthermore, hochuekkito treatment significantly reduced serum IL-6 level and IL-6 expression level in macrophages in tissues surrounding the tumor. In vitro studies showed that hochuekkito suppressed the production of IL-6 by THP-1 or RAW264.7 macrophage cells, although it did not affect IL-6 production by colon 26 carcinoma cells. These results suggest that hochuekkito inhibits the production of proinflammatory cytokines, particularly IL-6, by host cells such as macrophages. Therefore, hochuekkito may be a promising anticachectic agent for the treatment of patients with cancer.

Section: Discussionmentioning

confidence: 99%

Hochuekkito (TJ-41), a Kampo Formula, Ameliorates Cachexia Induced by Colon 26 Adenocarcinoma in Mice

Takahashi

Evidence-Based Complementary and Alternative Medicine

et al. 2012

Clinical Cancer Research

“…25). Naoe et al (26) showed that a significant decrease in the circulating levels of triglyceride was found in the salinetreated tumor-bearing mice compared with the saline-treated normal mice. In the present study, DHMEQ significantly inhibited the decrease of epididymal fat weight and serum triglycerides, presumably through the suppression of IL-6 production.…”

Section: Discussionmentioning

confidence: 99%

Prevention of Cancer Cachexia by a Novel Nuclear Factor κB Inhibitor in Prostate Cancer

Kuroda

Horiguchi

Nakashima

et al. 2005

Purpose: To investigate the association between serum interleukin-6 (IL-6) and cachexia in patients with prostate cancer and the inhibitory effect of a new nuclear factor nB (NF-nB) inhibitor, dehydroxymethylepoxyquinomicin (DHMEQ), on IL-6 production and cachexia in an animal model of hormone-refractory prostate cancer. Experimental Design:The association between serum IL-6 levels and variables of cachexia was evaluated in 98 patients with prostate cancer. The inhibitory effects of DHMEQ on IL-6 secretion and cachexia were investigated in in vitro and in vivo studies usingJCA-1cells derived from human prostate cancer. Results: Serum IL-6 levels were significantly elevated and cachexia developed in JCA-1 tumorbearing mice as well as in prostate cancer patients with progressive disease. IL-6 secretion was significantly inhibited inJCA-1cells exposed to DHMEQ. Intraperitoneal administration of DHMEQ (8 mg/kg) to tumor-bearing mice produced a significant amelioration of the reduction in body weight, epididymal fat weight, gastrocnemius muscle weight, hematocrit, and serum levels of triglyceride and albumin when compared with administration of DMSO or no treatment. DHMEQ caused a significant decrease of serum IL-6 level in JCA-1tumor-bearing mice (all P < 0.05). Conclusions:These results suggested an association between serum IL-6 and cachexia in patients with prostate cancer and in JCA-1 tumor-bearing mice and that a new NF-nB inhibitor, DHMEQ, could prevent the development of cachexia in JCA-1 tumor-bearing mice presumably through the inhibition of IL-6 secretion. DHMEQ seems to show promise as a novel and unique anticachectic agent in hormone-refractory prostate cancer.

“…3), although, in the LX‐1 models, body weight could not be evaluated due to cachexia at the later stage of treatment. ( 23,24 )…”

Section: Resultsmentioning

confidence: 99%

“…3), although, in the LX-1 models, body weight could not be evaluated due to cachexia at the later stage of treatment. (23,24) Effect of trastuzumab, tegafur/uracil or gefitinib in combination with amrubicin in human cancer xenograft models. Next, we examined the effects of trastuzumab, tegafur/uracil or gefitinib combined with amrubicin in vivo using human tumor xenograft models.…”

Section: Effect Of Chemotherapeutic Agents In Combination With Amrubicinmentioning

confidence: 99%

Amrubicin, a novel 9‐aminoanthracycline, enhances the antitumor activity of chemotherapeutic agents against human cancer cells in vitro and in vivo

Hanada¹,

Noguchi²,

Yamaoka³

2007

Cancer Science

Amrubicin, a completely synthetic 9-aminoanthracycline derivative, is an active agent in the treatment of untreated extensive diseasesmall-cell lung cancer and advanced non-small-cell lung cancer. Amrubicin administered intravenously at 25 mg/kg substantially prevented the growth of five of six human lung cancer xenografts established in athymic nude mice, confirming that amrubicin as a single agent was active in human lung tumors. To survey which antitumor agent available for clinical use produces a synergistic interaction with amrubicin, we examined the effects in combinations with amrubicinol, an active metabolite of amrubicin, of several chemotherapeutic agents in vitro using five human cancer cell lines using the combination index (CI) method of Chou and Talalay. Synergistic effects were obtained on the simultaneous use of amrubicinol with cisplatin, irinotecan, gefitinib and trastuzumab, with CI values after 3 days of exposure being <1. Additive effect was observed with the combination containing vinorelbine with CI values indistinguishable from 1, while the combination of amrubicinol with gemcitabine was antagonistic. All combinations tested in vivo were well tolerated. The combinations of cisplatin, irinotecan, vinorelbine, trastuzumab, tegafur/uracil, and to a lesser extent, gemcitabine with amrubicin caused significant growth inhibition of human tumor xenografts without pronouncedly enhancing body weight loss, compared with treatment using amrubicin alone at the maximum tolerated dose. (1) Small-cell lung cancer (SCLC) accounts for approximately 15 -20% of all cases of lung cancer. Although SCLC is highly responsive to initial chemotherapy, response durations are short. Since a phase III trial in patients with extensive disease (ED)-SCLC demonstrated that a combination of cisplatin and irinotecan yielded a highly significant improvement in survival over a standard regimen consisting of cisplatin and etoposide, the former combination is now considered standard treatment for ED-SCLC.(2) Patients who fail to respond to first-line chemotherapy or relapse within 3 months after completion of first-line chemotherapy tend to do poorly. Non-small-cell lung cancer (NSCLC) comprises approximately 80-90% of lung cancers, and the majority of patients have locally advanced stage III or metastatic stage IV cancer at diagnosis. Combination chemotherapy has achieved overall response rates of 25-50% against NSCLC, however, NSCLC remains generally refractory to systemic chemotherapy compared with SCLC. At around 1990, new active agents including irinotecan, paclitaxel, docetaxel, gemcitabine, and vinorelbine, were introduced for cancer chemotherapy. A randomized study by the Southwest Oncology Group showed that paclitaxel plus carboplatin was equally efficacious as vinorelbine plus cisplatin. A study by the Eastern Cooperative Oncology Group found no significant difference in survival among four commonly used platinum-based regimens: cisplatin and paclitaxel, cisplatin and gemcitabine, cisplatin and docetaxel, or carbopl...