• Journal of Life Science
• /
• v.19 no.6
• /
• pp.770-780
• /
• 2009

A new photosensitizer, 9-Hydroxypheophorbide-a (9-HpbD-a), was derived from Spirulina platensis. We conducted a series of experiments, in vitro and in vivo, to evaluate the anticancer effect and mechanism of photodynamic therapy using 9-HpbD-a and 660 nm diode lasers on a squamous carcinoma cell line. We studied the cytotoxic effects of pheophytin-a, 9-HpbD-a, 9-HpbD-a red and 660 nm diode lasers in a human head and neck cancer cell line (SNU-1041). Cell growth inhibition was determined by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) reduction assay. The effects of 9-HpbD was higher than those of 9-HpbD-a red or pheophytin-a in PDT. We then tested the cytotoxic effects of 9-hydroxypheophorbide-a (9-HpbD-a) in vitro. The cultured SNU-I041 cells were treated with serial concentrations of 9-HpbD-a followed by various energy doses (0, 0.1, 0.5, 3.2 J/$cm^{2}$) and by various interval times (0, 3, 6, 9, 12 hr) until laser irradiation, then MTT assay was applied to measure the relative inhibitory effects of photodynamic therapy (PDT). Optimal laser irradiation time was 30 minutes and the cytotoxic effects according to incubation time after 9-HpbD-a treatment increased until 6 hours, after which it then showed no increase. To observe the cell death mechanism after PDT, SUN-I041 cells were stained by Hoechst 33342 and propidium iodide after PDT, and observed under transmission electron microscopy (TEM). The principal mechanism of PDT at a low dose of 9-HpbD-a was apoptosis, and at a high dose of 9-HpbD-a it was necrosis. PDT effects were also observed in a xenografted nude mouse model. Group I (no 9-HpbD-a, no laser irradiation) and Group II (9-HpbD-a injection only) showed no response (4/4, 100%), and Group III (laser irradiation only) showed recurrence (1/4,25%) or no response (3/4, 75 %). Group IV (9-HpbD-a + laser irradiation) showed complete response (10/16, 62.5%), recurrence (4/16, 25%) or no response (2/16, 12.5%). Group IV showed a significant remission rate compared to other groups (p<0.05). These results suggest that 9-HpbD-a is a promising photosensitizer for the future and that further studies on biodistribution, toxicity and mechanism of action would be needed to use 9-HpbD-a as a photosensitizer in the clinical setting.

• Asian Pacific Journal of Cancer Prevention
• /
• v.15 no.11
• /
• pp.4395-4403
• /
• 2014

Nowadays there are several limitations in cancer treatment. One of these is the use of conventional medicines which not only target cancer cells and thus also cause high toxicity precluding effective treatment. Recent elucidation of mechanisms that cause cancer has led to discovery of novel key molecules and pathways which have have become successful targets for the treatments that eliminate only cancer cells. These so-called targeted therapies offer new hope for millions of cancer patients, as briefly reveiwed here focusing on different types of agents, like PARP, CDK, tyrosine kinase, farnysyl transferase and proteasome inhibitors, monoclonal antibodies and antiangiogenic agents.

• Asian Pacific Journal of Cancer Prevention
• /
• v.14 no.2
• /
• pp.609-617
• /
• 2013

Renal cell carcinomas make up 3% of all cancers and one in four patients is metastatic at time of diagnosis. This cancer is one of the most resistant to cytotoxic chemotherapy. Studies have shown that the efficiency of interferon-alpha and/or interleukin-2 based immune therapies is limited in patients with metastatic renal cell carcinoma but latest advances in molecular biology and genetic science have resulted in better understanding of its biology. Tumor angiogenesis, tumor proliferation and metastasis develop by the activation of signal message pathways playing a role in the development of renal cell carcinomas. Better definition of these pathways has caused an increase in preclinic and clinical studies into target directed treatment of renal cell carcinoma. Many recent studies have shown that numerous anti-angiogenic agents have marked clinical activity. In this article, the focus is on general characteristics of molecular pathways playing a major role in renal cell carcinoma, reviewing clinical information onagents used in the target directed treatment of metastatic lesions.

• BMB Reports
• /
• v.47 no.3
• /
• pp.122-129
• /
• 2014

Although considerable progress has been made in understanding how tumors evade immune surveillance, measures to counter the same have not kept pace with the advances made in designing effective strategies. 4-1BB (CD137; TNFRS9), an activation-induced costimulatory molecule, is an important regulator of immune responses. Targeting 4-1BB or its natural ligand 4-1BB ligand (4-1BBL) has important implications in many clinical conditions, including cancer. In-depth analysis revealed that 4-1BB-mediated anti-cancer effects are based on its ability to induce activation of cytotoxic T lymphocytes (CTL), and among others, high amounts of IFN-${\gamma}$. In this review, we will discuss the various aspects of 4-1BB-mediated anti-tumor responses, the basis of such responses, and future directions.

• Bulletin of the Korean Chemical Society
• /
• v.28 no.11
• /
• pp.1931-1938
• /
• 2007

Analyzed are recent advances in design of novel boronared conjugates of synthetic and natural porphyrins and chlorins. These compounds showed high efficacy as cytotoxic agents for tumor cells in culture and as phototoxins in photodynamic therapy of tumor xenografts. Thus, boronated porphyrins and chlorins emerge as promising class of anticancer agents with potentially multiple advantages: the chemotherapeutic drugs alone and photo- and radiosensitizers in binary treatments.

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.130.1-130.1
• /
• 2003

As a potent antigen presenting cells and a powerful inducer of antigen specific immunity including cytotoxic T cell activity, dendritic cells(DCs) are being considered as a promising anti-tumor therapeutic module. Unlike solid tumors, leukemia is the hematologic malignancy involving immune effector cells. The expected usage of DCs in leukemia is the treatment of minimal residual disease(MRD) after the remission or stem cell transplantation. In this study, syngeneic leukemia cells were inoculated intra-venously into the mouse (WEHI-3 into the Balb/c), and the autologous tumor cell lysate pulsed DCs were injected as a therapeutic module twice in two weeks. (omitted)

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.137.2-137.2
• /
• 2003

Dendritic cells (DCs) are known to professional antigen presenting cell (APC). Due to the role as an effective activator of cytotoxic T Lymphocytes by expressing MHC, adhesion and co-stimulatory molecules, DCs are now widely recognized to play an important role in the immune responses to tumors.We investigated the effect of cultured DCs in murine melanoma pulmonary metastasis model. To follow the metastasis protocol, syngenic melanoma cells were inoculated intra-venously into the mouse (B16F10 into the C57BL/6)8 days prior to the first DC injection (1$\times$106 DCs/ mouse, i.p.) and the autologous tumor cell lysate pulsed-DCs were injected as a therapeutic module twice in two weeks. (omitted)

• Proceedings of the PSK Conference
• /
• 2003.10b
• /
• pp.204.2-204.2
• /
• 2003

The aqueous extract of European mistletoe (Viscum album, L.) has been used in cancer therapy. The purified mistletoe lectins, main components of mistletoe, have demonstrated cytotoxic and immune-system-stimulating activities. Korean mistletoe (Viscum album L. coloratum), a subspecies of European mistletoe, has also been reported to possess anticancer and immunological activities. A galactose- and N-acetyl-D-galactosamine- specific lectin (Viscum album L. coloratum agglutinin, VCA) with Mr 60 kDa was isolated from Korean mistletoe. (omitted)

• IMMUNE NETWORK
• /
• v.16 no.2
• /
• pp.134-139
• /
• 2016

Programmed death-1 (PD-1) is a strong negative regulator of T lymphocytes in tumor-microenvironment. By engaging PD-1 ligand (PD-L1) on tumor cells, PD-1 on T cell surface inhibits anti-tumor reactivity of tumor-infiltrating T cells. Systemic blockade of PD-1 function using blocking antibodies has shown significant therapeutic efficacy in clinical trials. However, approximately 10 to 15% of treated patients exhibited serious autoimmune responses due to the activation of self-reactive lymphocytes. To achieve selective activation of tumor-specific T cells, we generated T cells expressing a dominant-negative deletion mutant of PD-1 (PD-1 decoy) via retroviral transduction. PD-1 decoy increased IFN-γ secretion of antigen-specific T cells in response to tumor cells expressing the cognate antigen. Adoptive transfer of PD-1 decoy-expressing T cells into tumor-bearing mice potentiated T cell-mediated tumor regression. Thus, T cell-specific blockade of PD-1 could be a useful strategy for enhancing both efficacy and safety of anti-tumor T cell therapy.

• IMMUNE NETWORK
• /
• v.1 no.1
• /
• pp.45-52
• /
• 2001

Background: Many types of cancer become resistant to current chemotherapeutic and radiotherapeutic intervention. To overcome this situation application of gene therapy by the introduction of suicide genes followed by their prodrugs may be promising. A viral enzyme, Herpes simplex thymidine kinase (HSV-tk), which converts ganciclovir from an inactive prodrug to a cytotoxic agent by phosphorylation, are being actively investigated for use in gene therapy for cancer. The purpose of this study was to determine whether combining prodrug-activating gene therapy and irradiation might result in enhanced antitumor effects. Methods: The HSV-tk gene was cloned into the retroviral vector, pLXSN and established the clones producing retroviruses carrying the HSV-tk gene. The carcinoma cell line, HCT116 and Huh-7 were transduced with high-titer recombinant retroviruses. These cell lines were treated with ganciclovir before or after irradiation for the defining combinational effect of suicide gene therapy and radiotherapy. Results: The titers of cloned PA3 17 amphotropic retroviruses ranged from 4 to 6 X $10^6CFU/ml4$. After selectional periods, the expression of HSV-tk was confirmed by reverse-transcriptase polymerase chain reaction (RT-PCR). The growth of cells expressing HSV-tk was inhibited as increase of GCV dose after 48 hr and the growth inhibitory effect of GCV was much higher after 72 hr. When the cells transduced with HSV-tk gene were exposed to radiation, the growth inhibitory effect of GCV was significantly increased, as compared with non-transduced parental cells. Conclusions: The results suggest that the addition of HSV-tk gene therapy to standard radiation therapy may improve the effectiveness of treatment for solid tumors.