Irradiation Enhances Proto-Oncogene c-erbB-2 Expression in Human Adenocarcinoma Cells

We investigated the effect of irradiation on the surface antigen expression of proto-oncogene c-erbB-2 on human adenocarcinoma cell lines. Cultured human colonic adenocarcinoma cell BM314 and gastric adenocarcinoma cells MKN45 were irradiated to investigate the expression of the Erb B-2 protein. Interferon-gamma (IFN-γ) was also used to treat these cancer cells. The expression of ErbB-2 showed remarkable increases on the surface of the membrane. Such upregulation was shown to be dose dependent, namely, higher radiation doses were associated with increased antigen expression. However, IFN-γ administ-ration did not show an increased expression of proto-oncogene c-erbB-2. These findings may explain partially the increased immunogenity of tumor cells following irradiation. The effect of irradiation is distinct from that of IFN-γ administration, suggesting that a different mechanism of action is present

Hypofractionated Stereotactic Radiotherapy (HypoFXSRT) for Stage I Non-small Cell Lung Cancer: Updated Results of 257 Patients in a Japanese Multi-institutional Study

IntroductionHypofractionated stereotactic radiotherapy (HypoFXSRT) has recently been used for the treatment of small lung tumors. We retrospectively analyzed the treatment outcome of HypoFXSRT for stage I non-small cell lung cancer (NSCLC) treated in a Japanese multi-institutional study.MethodsThis is a retrospective study to review 257 patients with stage I NSCLC (median age, 74 years: 164 T1N0M0, 93 T2N0M0) were treated with HypoFXSRT alone at 14 institutions. Stereotactic three-dimensional treatment was performed using noncoplanar dynamic arcs or multiple static ports. A total dose of 18 to 75 Gy at the isocenter was administered in one to 22 fractions. The median calculated biological effective dose (BED) was 111 Gy (range, 57–180 Gy) based on α/β = 10.ResultsDuring follow-up (median, 38 months), pulmonary complications of above grade 2 arose in 14 patients (5.4%). Local progression occurred in 36 patients (14.0%), and the local recurrence rate was 8.4% for a BED of 100 Gy or more compared with 42.9% for less than 100 Gy (p< 0.001). The 5-year overall survival rate of medically operable patients was 70.8% among those treated with a BED of 100 Gy or more compared with 30.2% among those treated with less than 100 Gy (p< 0.05).ConclusionsAlthough this is a retrospective study, HypoFXSRT with a BED of less than 180 Gy was almost safe for stage I NSCLC, and the local control and overall survival rates in 5 years with a BED of 100 Gy or more were superior to the reported results for conventional radiotherapy. For all treatment methods and schedules, the local control and survival rates were better with a BED of 100 Gy or more compared with less than 100 Gy. HypoFXSRT is feasible for curative treatment of patients with stage I NSCLC

The enhanced expression of the matrix metalloproteinase 9 in nasal NK/T-cell lymphoma

<p>Abstract</p> <p>Background</p> <p>Nasal NK/T cell lymphoma is an aggressive disease and has a poor prognosis. Nasal NK/T cell lymphoma is refractory to conventional chemotherapy and has strong tendency of widespread relapse or dissemination into distant sites.</p> <p>Methods</p> <p>We immunohistochemically studied nasal NK/T-cell lymphoma to elucidate the unique characteristics of nasal NK/T-cell lymphoma, such as its higher metastatic tendency and its vast necrosis which leads to destruction of the involved tissues. The expression of P-glycoprotein and MMP-9 was evaluated in the 20 patients with nasal NK/T-cell lymphoma and 25 with nasal non-NK/T-cell lymphoma and the relationship between expression of these proteins and clinical results were analyzed in this report.</p> <p>Results</p> <p>Overall 5-year survival rates for patients with nasal NK/T cell lymphoma, and nasal non-NK/T cell lymphoma were 51%, and 84%. Distant involvement free 5-year survival rates for patients with nasal NK/T cell lymphoma, and nasal non-NK/T cell lymphoma were 53%, and 79%.</p> <p>Overall positivity for P-glycoprotein was observed in 10 of 19 patients with NTL and in 13 of 23 patients with non-NTL. When the overall survival rate was compared between patients with P-glycoprotein positive and negative, there was no difference between them.</p> <p>Sixteen of the 19 patients with nasal NK/T cell lymphoma expressed MMP-9. In contrast, only 8 of the 22 patients with nasal non-NK/T cell lymphoma expressed MMP-9. Distant involvement free 5-year survival rates for patients with MMP-9 negative, and MMP-9 positive were 92%, and 61%, respectively. The difference was statistically significant (p = 0.027).</p> <p>Conclusion</p> <p>Positive immunoreactivity for P-glycoprotein was not an independent prognostic factor in nasal NK/T-cell lymphomas, which stresses the importance of exploring other mechanisms of drug resistance. The strong expression of MMP-9 is uniquely characteristic of nasal NK/T cell lymphoma and may contribute to its strong tendency to disseminatate and the extensive necrosis which is always seen. However, our results are based on univariate comparisons, and as such, should be viewed with some caution.</p