PDT with photofrin II has an excellent effect on patients with centrally located early-stage lung cancer who have limited tumor invasion extending over a small area (< or = 1 cm).

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We attempted to investigate immunohistochemical expression of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), platelet-derived growth factor (PD-ECGF), c-erbB-2, matrix metalloproteinase-2 (MMP-2), and MMP-9 using surgical specimens of 119 non-small-cell lung carcinoma (NSCLC) cases and to evaluate the relationship between the expression levels of each molecule and clinicopathological factors or prognosis. VEGF expression levels were significantly associated with the local invasion (P = 0.0001), lymph node involvement (pN-factor) (P = 0.0019), pathological stage (p-stage) (P = 0.0027) and lymphatic permeation (P = 0.0389). PD-ECGF expression levels were associated with pN-factor (P = 0.0347). MMP-2 expression levels were associated with pN-factor (P = 0.004) and lymphatic permeation (P = 0.0056). Also, MMP-9 expression levels showed a significant correlation to local invasion (P = 0.0012), pN-factor (P = 0.0093) and p-stage (P = 0.0142). Multivariate analysis showed VEGF to be the most related to local invasion (P = 0.0084), and MMP-2 was the only factor with significant independent impact on lymphatic permeation (P = 0.0228). Furthermore, log-rank analysis showed significant association with poor survival by VEGF, bFGF, MMP-2 and MMP-9. Especially, combined overexpression of VEGF and MMP-2 revealed poor prognosis, our study might provide a basis for the better evaluation of biological characteristics and a new therapeutic strategy based on chemotherapy. © 2001 Cancer Research Campaign http://www.bjcancer.com

PDT has been reported to induce cancer cell expression of cytokines, such as IL-6 and TNF-␣, but it has been unclear whether cytokine expression by cancer cells is directly related to the antitumor effect of PDT. We treated Lewis lung carcinoma (LLC) cells with a new photosensitizer, mono-Laspartyl chlorin e6 (NPe6) and light from a diode laser and found that expression of the mRNA of IL-2, IL-6, and TNF-␣ was increased by NPe6-mediated-PDT 6 hr later. To elucidate the mechanism of the direct anti-tumor effect of cytokine expression, we examined the photosensitivity of cytokine- To enhance the potential of PDT and to extend its clinical applications, a second generation of photosensitizers is now being assessed, and it is important to elucidate their mechanism of action in PDT. Mono-L-aspartyl chlorin e6 (NPe6) is a water-soluble substance, and NPe6-mediated-PDT has been shown to have an antitumor effect in several experimental models and is currently undergoing clinical evaluation in Japan.Granville et al. 3 reported that PDT induces apoptosis in various tumor cell lines. PDT also induces nonspecific and specific immune responses against tumors in vitro and in vivo. Krosl et al. 4 reported that the antitumor efficacy of PDT is improved by the administration of macrophage activating factors such as granulocyte-macrophage colony activating factor (GM-CSF), whereas Gollnick et al. 5 demonstrated that PDT alters expression of IL-6 and IL-10 in vivo. The immune mechanisms of PDT have never been clarified, however, and it is unknown whether cytokine expression is involved in the antitumor effects of PDT. To elucidate the immune response and the mechanisms of action involved in NPe6-mediated PDT, we examined the effects of cytokine overexpression on PDT by using cytokine gene transfected cells and we have characterized the apoptotic mechanism. MATERIAL AND METHODS Laser light delivery systemA new high-power red laser diode system (Matsushita Industrial Equipment Co., Osaka, Japan), with potential for use in photodynamic therapy (PDT) with NPe6, was employed. This system has a power output of 10 -500 mW/cm 2 at the fiber tip. The irradiation mode is continuous wave (CW), and the delivered energy can be adjusted from 1-1,000 J/cm.2 . 2 Although it runs on 100 V current, the system is 49 ϫ 20 ϫ 40 cm in size, weighs 20 kg, and is easy to take into a sickroom. The power of the laser is easily adjusted, the wavelength of the light is stable (within 0.2 nm), and it is delivered through a quartz fiber. The full width at half maximum is less than 2 nm, which enables uniform, high-density photoradiation, and the power density distribution of the laser, analyzed by a charge-coupled device (CCD) camera, is uniform throughout the photoradiated field. In our study, the diode laser wavelength was adjusted to 664 nm to match the absorption bands of NPe6. PHOTOSENSITIZERCompound NPe6 is an effective photosensitizer that possesses properties such as chemical purity and a major absorption band at 664 nm, features that are potentiall...

Airway stenting followed by adjuvant therapy may improve the survival of treatment-naïve patients with severe symptomatic airway obstruction caused by advanced lung cancer.

An historical overview is given of the development of photodynamic therapy (PDT) with hematoporphyrin derivative for the treatment of malignant tumors. Results in patients with superficial, and non‐superficial esophageal cancer and with early gastric cancer is described, with case illustrations and follow‐up. Due to the difficulty in early stage diagnoses and in determining all cases of lymph node involvement, mis form of treatment should be employed primarily in inoperable early‐stage cancer, to reduce the extent of resection, or to render previously inoperable cases operable. Combination with other treatment modalities and the effects of PDT on histologically different tumor types, need to be further examined.

It is known that HpD is retained longer by malignant tissue than normal tissue and is therefore a useful material for photodynamic therapy (PDT). Currently, vigorous research is being conducted throughout the world to discover a new material which can have greater cancer cell affinity than hematoporphyrin derivative (HpD) and will be used effectively for PDT. Investigation has been conducted to determine the spectral characteristics and cancer cell affinity of NPe6, a recently developed material. Structurally, a double bond on the D‐ring of the porphyrin ring of mono‐L‐aspartyl chlorin e6 (NPe6) has been reduced, thereby changing its spectral properties from that of HpD. This difference accounts for the stronger absorption bands in wavelengths longer than those of HpD. Furthermore, NPe6 in tumor showed stronger absorption at 660 nm than HpD. Absorption by hemoglobin (Hb) in the blood occurs at wavelengths in the range 500‐600 nm, thereby lowering light transmittance. A compound which has a strong absorption band at wavelengths longer than 600 nm and consequently is not affected by Hb will naturally be activated by light at a greater depth in tissue than compounds which do not share this characteristic. The localization of NPe6 in sarcoma and various internal organs was examined with an endoscopic spectrophotometer using an excimer dye laser. After 72 h i.v. NPe6 injection, the results indicate that NPe6 has 10 times greater uptake in malignant tissue cells than in normal organs. Based on the above observations, it was concluded that NPe6 could be effective for PDT if toxicity is low and that this compound has a high malignant tissue affinity.