Cancer Immunol Immunother
June 2010
Interleukin-17E (IL-17E) belongs to a novel family of cytokines that possess significant homology to IL-17. IL-17E has potent inflammatory effects in vitro and in vivo. Overexpression of IL-17E in mice results in a T helper-2 (Th2)-type immune response, which includes the expansion of eosinophils through the production of IL-5, and elevated gene expression of IL-4 and IL-13 in multiple tissues.
View Article and Find Full Text PDFML-133 is a novel small molecule with potent antiproliferative activity, as shown in cancer cell lines and in a human colon tumor xenograft model. ML-133 reduces the concentration of intracellular labile zinc in HT-29 colon cancer cells, leading to induction of the Krüppel-like factor 4 transcription factor. Krüppel-like factor 4 displaces the positive regulator SP1 from the cyclin D1 promoter, thereby negatively regulating the expression of cyclin D1 and promoting the G(1)-S phase arrest of cell proliferation.
View Article and Find Full Text PDFGTI-2040, an antisense oligonucleotide targeting the small subunit of ribonucleotide reductase, acts as an anti-tumor agent in animal models of human cancer. In the present study, the anti-tumor activity of GTI-2040, in combination with interferon alpha (IFNalpha) was investigated against human renal cell carcinoma tumors xenografted into mice. The human renal cell carcinoma cell lines, Caki-1 and A498 were sensitive to IFNalpha both in vitro and when implanted into mice.
View Article and Find Full Text PDFCancer Immunol Immunother
December 2008
Virulizin has demonstrated strong antitumor efficacy in a variety of human tumor xenograft models including melanoma, pancreatic cancer, breast cancer, ovarian cancer and prostate cancer. Our previous studies have demonstrated that macrophages, NK cells, and cytokines are important in the antitumor mechanism of Virulizin. Virulizin treatment of tumor bearing mice results in the expansion as well as increased activity of monocytes/macrophages and production of cytokines IL-12 and TNFalpha and activation of NK cells.
View Article and Find Full Text PDFVirulizin, a novel biological response modifier, has demonstrated broad antitumor efficacy in a variety of human tumor xenograft models including melanoma, pancreatic cancer, breast cancer, ovarian cancer and prostate cancer. Previous studies have demonstrated a significant role of macrophages and NK cells in the antitumor mechanism of Virulizin. Increased activity and expansion of macrophages and NK cells has been observed in mice treated with Virulizin.
View Article and Find Full Text PDFRNA interference, a posttranscriptional gene-silencing mechanism, has received considerable attention for its potential as a new therapeutic strategy to treat human diseases and conditions including cancer. Various studies have supported a role for the R2 subunit of ribonucleotide reductase in cancer progression and metastasis. Short interfering siRNA 1284 was designed to target R2.
View Article and Find Full Text PDFHuman thioredoxin has been implicated in cancer as a growth stimulator through regulation of DNA replication and growth factor activity, as a modulator of transcription factor activity, and as an inhibitor of apoptosis. In the present study, the steady-state level of thioredoxin protein was examined in a number of cancer cell lines. Interestingly, thioredoxin expression is elevated in a variety of human tumor cell lines compared with normal cell lines.
View Article and Find Full Text PDFGTI-2501 is a 20-mer oligonucleotide that is complementary to a coding region in the mRNA of R1, the large subunit of ribonucleotide reductase (RNR). In vitro studies, have demonstrated that GTI-2501 decreases mRNA and protein levels of R1 in a sequence-specific and dose-dependent manner. Furthermore, GTI-2501 inhibits the growth of human lung, liver, ovary, brain, melanoma, breast and pancreatic tumor cells in colony forming assays.
View Article and Find Full Text PDFCancer Immunol Immunother
November 2005
Virulizin, a novel biological response modifier, has demonstrated significant antitumor efficacy in a variety of human tumor xenograft models including melanoma, pancreatic cancer, breast cancer, ovarian cancer and prostate cancer. The significant role of macrophages and NK (Natural killer) cells was implicated in the antitumor mechanism of Virulizin where expansion as well as increased activity of macrophages and NK cells were observed in mice treated with Virulizin. Depletion of macrophages compromised Virulizin-induced NK1.
View Article and Find Full Text PDFCancer Immunol Immunother
March 2005
Previous studies have demonstrated antitumor efficacy of Virulizin in several human tumor xenograft models and a critical role for macrophages in the antitumor mechanism of Virulizin. Although there is growing support for an immune stimulatory mechanism of action for Virulizin, the details remain to be elucidated. The aim of this study was to determine whether infiltration of natural killer (NK) cells into xenografted tumors is altered by Virulizin treatment, and whether such alterations contribute to the antitumor activity of Virulizin.
View Article and Find Full Text PDFAlthough clotrimazole (CLT), an antifungal drug, inhibits tumor cell proliferation and angiogenesis, its clinical application is hampered by significant hepatotoxicity due to the presence of an imidazole moiety. In our attempts to develop CLT analogs that are devoid of imidazole and are as efficacious as CLT, one pharmacophore designated NC381 was generated and shown to inhibit tumor cell growth via a mechanism similar to that of CLT. In vitro, treatment of NCI-H460 nonsmall cell lung cancer (NSCLC) cells with NC381 inhibited growth in a time-dependent manner.
View Article and Find Full Text PDFRibonucleotide reductase is the enzyme responsible for the reduction of ribonucleotides to their corresponding deoxyribonucleotides for DNA synthesis. Ribonucleotide reductase is a multisubunit complex containing two polypeptides, R1 and R2. In addition to catalytic and allosteric regulatory functions, the R1 subunit appears to act as a novel tumor suppressor.
View Article and Find Full Text PDFVirulizin, a novel biological response modifier (BRM), has been demonstrated to have a high level of anti-tumor activity against pancreatic cancer and melanoma in many clinical trials and preclinical studies. However, its anti-tumor mechanism has not been fully elucidated. The purpose of this study was to define the mechanism of Virulizin anti-tumor activity in cultures and in a murine xenograft model.
View Article and Find Full Text PDFGTI-2040 is a 20-mer oligonucleotide that is complementary to a coding region in the mRNA of the R2 small subunit component of human ribonucleotide reductase. In vitro studies using a number of human tumor cell lines have demonstrated that GTI-2040 decreases mRNA and protein levels of R2 in a sequence- and target-specific manner. In vivo studies have shown that GTI-2040 significantly inhibits growth of human colon tumors (adenocarcinoma), pancreatic tumors (adenocarcinoma), liver tumors, lung tumors, breast tumors (adenocarcinoma), renal tumors, ovarian tumors (adenocarcinoma), melanoma, brain glioblastoma-astrocytoma, prostatic tumors, and cervical tumors in nude and/or severe combined immunodeficient mice.
View Article and Find Full Text PDFVirulizin is a novel biological response modifier (BRM) approved for the treatment of melanoma and is currently in a phase III clinical trial against advanced pancreatic cancer. The purpose of this study was to define the anti-cancer activity of Virulizin against a number of solid human tumors. The therapeutic effect of Virulizin was evaluated in mouse xenograft models, and the results demonstrate that Virulizin has high efficacy against breast, ovarian and prostate tumor xenografts.
View Article and Find Full Text PDFPurpose: To define the anticancer efficacy of Virulizin in vivo as a single agent or in combination with conventional drugs in human pancreatic tumor and melanoma xenografts.
Methods: The therapeutic effect of Virulizin was evaluated in a series of human tumor xenografts in athymic nude mice.
Results: Virulizin had a high level of antitumor activity against all the pancreatic tumors (BxPC-3, SU 86.