Oncology Research 

About: Oncology Research is an academic journal published by Cognizant Communication Corporation. The journal publishes majorly in the area(s): Cell growth & Cancer. It has an ISSN identifier of 0965-0407. Over the lifetime, 1819 publications have been published receiving 41112 citations. The journal is also known as: Oncology research incorporating anti-cancer drug design,.

KRN7000, a novel immunomodulator, and its antitumor activities.

Abstract: KRN7000, a compound with a novel alpha-galactosylceramide structure, showed potent tumor growth inhibitory activities in B16-bearing mice and markedly stimulated lymphocytic proliferation in allogeneic mixed leukocyte reaction, suggesting that KRN7000 is a biological response modifier. To confirm this suggestion, we examined the abilities of KRN7000 to enhance in vitro and in vivo natural killer (NK) activities, and found that KRN7000 enhanced in vitro and in vivo NK activities, and its potency on in vivo NK activity was much stronger than those of Poly I:C, which is a positive control, or the representative BRMs OK432 and Lentinan. In addition, since spleen cells intravenously treated with KRN7000 also showed potent cytotoxic activities against B16 and EL-4 cells, we evaluated the capability of KRN7000 to prolong the survival period of mice intravenously inoculated with B16 cells or mice intraperitoneally inoculated with EL-4 cells. In these models, KRN7000 (100 micrograms/kg) significantly prolonged the lifespan of mice, and its potency was stronger than that of Mitomycin C, a typical chemotherapeutic agent, in two models. These results demonstrate that KRN7000 would be a useful agent for cancer therapy.

Involvement of claudin-1 in the beta-catenin/Tcf signaling pathway and its frequent upregulation in human colorectal cancers.

Abstract: Accumulation of beta-catenin in cytoplasm and nuclei is frequently observed in a wide variety of tumors arising, for example, in the colon, liver, uterus, or brain. In association with Tcf/LEF transcription factors, beta-catenin regulates expression of genes involved in the Wnt/wingless signaling pathway, but the precise mechanisms are unclear. Here we report evidence that the claudin-1 (CLDNI) gene is one of the genes regulated by beta-catenin. Not only did expression of CLDN1 decrease significantly in response to reduction of intracellular beta-catenin by adenovirus-mediated transfer of wild-type APC into the APC-deficient colon cancer cells, but also two putative Tcf4 binding elements in the 5' flanking region of CLDN1 were confirmed to be responsible for activating its transcription. We documented increased expression of CLDN1 in all 16 primary colorectal cancers we examined, compared with adjacent noncancerous mucosae. Furthermore, immunohistochemical staining demonstrated that claudin-1 was weakly stained at apical boarder of lateral membrane of noncancerous epithelial cells and that it was strongly stained at all cell-cell boundaries and in the cytoplasms of cancer cells. Our results imply that claudin-1 is involved in the beta-catenin-Tcf/LEF signaling pathway, and that increased expression of claudin-1 may have some role in colorectal tumorigenesis.

Targeting gene therapy to cancer: a review.

Abstract: In recent years the idea of using gene therapy as a modality in the treatment of diseases other than genetically inherited, monogenic disorders has taken root This is particularly obvious in the field of oncology where currently more than 100 clinical trials have been approved worldwide This report will summarize some of the exciting progress that has recently been made with respect to both targeting the delivery of potentially therapeutic genes to tumor sites and regulating their expression within the tumor microenvironment In order to specifically target malignant cells while at the same time sparing normal tissue, cancer gene therapy will need to combine highly selective gene delivery with highly specific gene expression, specific gene product activity, and, possibly, specific drug activation Although the efficient delivery of DNA to tumor sites remains a formidable task, progress has been made in recent years using both viral (retrovirus, adenovirus, adeno-associated virus) and nonviral (liposomes, gene gun, injection) methods In this report emphasis will be placed on targeted rather than high-efficiency delivery, although those would need to be combined in the future for effective therapy To date delivery has been targeted to tumor-specific and tissue-specific antigens, such as epithelial growth factor receptor, c-kit receptor, and folate receptor, and these will be described in some detail To increase specificity and safety of gene therapy further, the expression of the therapeutic gene needs to be tightly controlled within the target tissue Targeted gene expression has been analyzed using tissue-specific promoters (breast-, prostate-, and melanoma-specific promoters) and disease-specific promoters (carcinoembryonic antigen, HER-2/neu, Myc-Max response elements, DF3/MUC) Alternatively, expression could be regulated externally with the use of radiation-induced promoters or tetracycline-responsive elements Another novel possibility that will be discussed is the regulation of therapeutic gene products by tumor-specific gene splicing Gene expression could also be targeted at conditions specific to the tumor microenvironment, such as glucose deprivation and hypoxia We have concentrated on hypoxia-targeted gene expression and this report will discuss our progress in detail Chronic hypoxia occurs in tissue that is more than 100-200 microns away from a functional blood supply In solid tumors hypoxia is widespread both because cancer cells are more prolific than the invading endothelial cells that make up the blood vessels and because the newly formed blood supply is disorganized Measurements of oxygen partial pressure in patients' tumors showed a high percentage of severe hypoxia readings (less than 25 mmHg), readings not seen in normal tissue This is a major problem in the treatment of cancer, because hypoxic cells are resistant to radiotherapy and often to chemotherapy However, severe hypoxia is also a physiological condition specific to tumors, which makes it a potentially exploitable target We have utilized hypoxia response elements (HRE) derived from the oxygen-regulated phosphoglycerate kinase gene to control gene expression in human tumor cells in vitro and in experimental tumors The list of genes that have been considered for use in the treatment of cancer is extensive It includes cytokines and costimulatory cell surface molecules intended to induce an effective systemic immune response against tumor antigens that would not otherwise develop Other inventive strategies include the use of internally expressed antibodies to target oncogenic proteins (intrabodies) and the use of antisense technology (antisense oligonucleotides, antigenes, and ribozymes) This report will concentrate more on novel genes encoding prodrug activating enzymes, so-called suicide genes (Herpes simplex virus thymidine kinase, Escherichia coli nitroreductase, E (ABSTRACT TRUNCATED)

Clinical evaluation of nitroimidazoles as modifiers of hypoxia in solid tumors.

Abstract: Hypoxic modification by nitroimidazoles has been explored in a large number of clinical studies Nine different drugs (misonidazole, metronidazole, benznidazole, desmethylmisonidazole, etanidazole, pimonidazole, nimorazole, ornidazole, and RSU 1069) have reached clinical evaluation Phase I and II trials have demonstrated a relationship between drug tolerance and expected hypoxic modification Thus, the most tolerable drugs, viz, 5-nitroimidazoles, are those with the smallest preclinical activity However, they may be the most clinically active, due to higher plasma and tumor concentrations The clinical evaluation of hypoxic modification is difficult, since clinically important hypoxia can be observed only indirectly There is, however, indirect evidence of substantial hypoxia in human tumors, although with considerable heterogeneity among individual tumors More than 7000 patients have been included in 50 randomized trials A meta-analysis showed that modification of tumor hypoxia significantly improved the loco-regional tumor control after radiotherapy with an odds ratio of 117 (95% confidence limits 106 to 128) The treatment benefit could mostly be related to an improved response in head and neck with odds ratio 123 (95% confidence limits 109 to 137), and to a lesser extent in bladder tumors; no significant effect was observed in other tumor sites (cervix, lung, central nervous system, and esophagus) Similarly to the local control benefit, the overall survival rate was improved with an overall odds ratio of 113 (95% confidence limits 103 to 123) The clinical trials showed no evidence of significant chemosensitization or direct bioreductive effect Although 50 randomized clinical trials were evaluated, the median number of patients was only 97 (range 17-620) Clinical trials of this size are not likely to detect the observed differences, which may explain the lack of significant improvement in most of the individual studies However, the overall results indicate that the biological issue related to hypoxia appears to be a sound rationale, especially with regard to head and neck and bladder carcinoma Future studies related to the hypoxic problem should therefore preferably be aimed towards such tumors

In vivo antimetastatic action of ginseng protopanaxadiol saponins is based on their intestinal bacterial metabolites after oral administration.

Abstract: The present study demonstrated in vivo and in vitro antimetastatic activities of a major intestinal bacterial metabolite M1 formed from protopanaxadiol saponins of ginseng (the root of Panax ginseng C. A. Meyer) in comparison with its whole standardized extract and ginsenosides Rb1, Rb2, and Rc. Although Ginseng extract (1 mg/mouse) and ginsenosides (0.5 mg/mouse) significantly inhibited lung metastasis produced by i.v. injection of B16-BL6 melanoma cells in syngeneic mice (27-61% of untreated control), they hardly inhibited the invasion and migration of B16-BL6 melanoma and HT1080 fibrosarcoma cells in vitro. However, the intestinal bacterial metabolite M1 inhibited lung metastasis of melanoma cells and in vitro tumor cell invasion and migration at nontoxic or marginally toxic concentrations. Additionally, pharmacokinetic studies of ginsenoside Rb1 and M1 after oral administration (2 mg/mouse) revealed that intact Rb1 was not detectable in serum for 24 h by HPLC analysis, whereas the level of M1 in the serum reached maximum at 8 h (8.5 +/- 0.4 micrograms/ml) after Rb1 administration and at 2 h (10.3 +/- 1.0 micrograms/ml) after M1 administration. These findings suggest that the in vivo antimetastatic effect by oral administration of ginsenosides is mediated by their metabolic component M1.