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Heparanase has been given attention for its role in the invasion and metastasis of various cancers for years. We have also investigated and reported the role of heparanase in several human cancers, including gastric, esophageal and colon carcinomas. Other than the critical role of heparanase in tumor invasion and metastasis, it is also believed that heparanase is involved in angiogenesis, another feature of tumor progression which is complicatedly mediated by many molecules, including cyclooxygenese-2 (Cox-2). Thus, our recent study elucidated a possible relationship of heparanase with Cox-2 upon tumor angiogenesis. Based upon our study, three major transcription factor binding sites containing NF-kappaB, NF-IL-6 and CRE sites seemed to have a compensative and cooperative role in heparanase-induced Cox-2 upregulation. On the other hand, tumor hypoxia often occurs in most tumors and Cox-2-induced HIF1alpha overexpression has recently been shown in various cancers. Here we believe that heparanase may also be involved in tumor hypoxia through the induction of HIFalpha either directly or indirectly through the Cox-2 pathway. This hypothesis indicates a possible novel function of heparanase and its link to HIF1alpha and Cox-2, and therefore this function would give us a clue about potential new strategies for cancer therapy.

The basic principle of radiotherapy for cancer patients is to establish a course of therapy which offers good prospects for a cure, has tolerable adverse effects, and promises a comfortable life for the patient thereafter. There have been two paths in the development of radiotherapy. One is physical, in which efforts have been made to improve the dose concentration on the tumor while avoiding healthy tissue, and the order is biological efforts to increase radiation susceptibility of tumors. Recently, computer medicine has improved radiation planning and made high quality radiotherapy possible. Elderly patients with cancer need to be treated with minimally invasive organ-preserving therapy techniques. Radiotherapy is an important tool for cancer treatment in the past, present and future.

Radiotherapy is of particular benefit to elderly patients as alternative surgery, and it is widely used with curative and palliative intent. Patients aged 75 and older accounted for 5-10% of all cases, and half of them had some complications. Radical radiotherapy was performed in 63-73% of the elderly patients and 88-100% were able to complete the planned course. Several authors reported that the elderly patients adequately staged, can tolerate radical radiotherapy and have survival comparable to that of younger patients. But careful management is needed.

The basic principle of radiotherapy for cancer patients is that it has the possibility of a good result (curability), is tolerable and promises a comfortable life thereafter. Radiotherapy is the important tool for early stage cancer by conserving the organ and function and for an advanced or recurrent stage of cancer by helping improve the quality of life. Radiotherapy must be planned on the basis of considering the therapeutic ratio with a 3-dimensional technique. It should be performed with optimum radiation methods in the multimodal treatment of cancer and will undoubtedly prove effective in the future.

As predictors of tumor response by radiotherapy, tumor with or without c-myc amplification and DNA histogram pattern were analyzed and evaluated for patients' prognosis. There was no relation between c-myc amplification and DNA ploidy pattern in this study. These factors also showed no relation to response rate and survival. But all of the tumors with c-myc amplification and aneuploid pattern exhibited a complete response by radiotherapy. The tumors with c-myc amplification and aneuploid pattern may be more radiosensitive than without amplification and diploid. These data suggested that c-myc amplification and ploidy pattern might be a predictive parameter before radiotherapy.

Considering the relationship between tumor lethal dose and normal tissue tolerance: the therapeutic ratio, radiation oncologists have been performed the radiotherapy for cancer patient. The basic principle of radiotherapy is to have a good result (curability), to be tolerable in side effects and to have a comfortable life after radiation. Radiotherapy is the important strategy for an early stage of cancer with conserving the function and structure, and for an advanced or a recurrent stage of cancer with contributing to improve the quality of life. Recently, advantage of radiation tools and supportive care of cancer treatment, have been able to decrease the incidence of late injuries and complications. Radiotherapy must be planned on basis of considering therapeutic ratio and should be performed with optimum radiation in the multimodal treatment for cancer.

The latest treatment of biological response modifiers (BRM) with or without another cancer treatment modalities has been increased. In this paper, radiotherapy combined with some BRM, which were used in systemic administration and intra-arterial infusion, was demonstrated. 1) In experimental study, radiation and IL-2 indicated the synergic effects on the tumor growth inhibition. 2) Radiotherapy and IFN-beta for advanced head and neck and pelvic tumor were successful in tumor effects and tolerable in side effects. 3) The clinical trial showed that pathological effects and clinical tumor response (CR rate) of radiation and LC9018 for cervical cancer stage IIb, III were significantly better than those of radiotherapy alone. These data suggested that the treatment of radiation and BRM was useful and should be considered in multimodal therapy for cancer.

Significance of combined therapy should be based in improvement of treatment results and decrease of side effects not only early but also late injuries. In other word, T.R. should be estimated whether direction of it is improvement or not. There are many different factors and difficult subjects which are decision of optimum dose, timing of combination, mechanism in synchronous combined therapy, distribution of tumor microcirculation. It is very important in order to improvement of T.R. clinically that we have been watching reactions after treatment closely and accumulating their datas.

The purpose of this paper is to report the clinical analysis and radiation strategy for cancer in the therapeutic ratio (T.R.) which were decided on relationship between tumor lethal dose and tissue tolerance. T.R. was first described at 1936, 40 years after discovering X-ray, by Holthusen. It is the basic principle of Radiotherapy for Radiation Oncologist. Radiotherapy must be planned on basing T.R. which is decided after estimating tumor factor, normal tissue tolerance, and host condition. In recent years, not only early skin reaction but late deep organs effects should be considered on T.R. because radiation energy has become higher from KeV era to MeV. The Optimum radiation methods has been investigated according to consider T.R.

A drug delivery catheter system with subcutaneously implantable port, PORT-A-CATH, was applied for intra-arterial, intravenous and intraperitoneal chemotherapy and hyperalimentation in treating 99 cancer patients. The average implantation period was 135.1 days and this system was applied for more than one year in 5 cases. Any troubles due to port or catheter materials were not observed during the study. Catheter occlusion occurred in 11 cases infection in 7 (catheter-related infection 4, pocket infection 3), and skin necrosis in 4. This system was proved useful to reduce the risk of infection and enabled easy and safe long-term repeated administration, compared to the catheters with external end. Intra-arterial chemotherapy became possible to the outpatients with the use of this system, which seemed to contribute for the improvement of quality of life of the patients.