Radiation-induced immune responses: mechanisms and therapeutic perspectives

Recent advancement in the radiotherapy technology has allowed conformal delivery of high doses of ionizing radiation precisely to the tumors while sparing large volume of the normal tissues, which have led to better clinical responses. Despite this technological advancement many advanced tumors often recur and they do so within the previously irradiated regions. How could tumors recur after receiving such high ablative doses of radiation? In this review, we outlined how radiation can elicit anti-tumor responses by introducing some of the cytokines that can be induced by ionizing radiation. We then discuss how tumor hypoxia, a major limiting factor responsible for failure of radiotherapy, may also negatively impact the anti-tumor responses. In addition, we highlight how there may be other populations of immune cells including regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) that can be recruited to tumors interfering with the anti-tumor immunity. Finally, the impact of irradiation on tumor hypoxia and the immune responses according to different radiotherapy regimen is also delineated. It is indeed an exciting time to see that radiotherapy is being combined with immunotherapy in the clinic and we hope that this review can add an excitement to the field.

Clinical implication of serum TNF-alpha and IL-1beta measurement in patients with sepsis / 결핵

BACKGROUND: It is well known that when macrophages are stimulated with endotoxin, they produce a wide variety of cytokine mediators, including TNF-α and IL-1β. However, there is an alterationnin the macrophages responsiveness when they are challenged with repeated bouts of endotoxin, termed 'endotoxin tolerance' which is regarded as a self-protective phenomenon from continuous stimulation. In this study, endotoxin tolerance in the peripheral blood monocytes of sepsis patients was evaluated. METHODS: Fourteen patients with organism-documented sepsis were included. The severity of illness was evaluated by APACHE IIscore. Peripheral blood monocytes were isolated from the patients and diluted to 1×105/well. After stimulation with endotoxin(LPS of E. coli O114:B4, 100 ng/ml), they were incubated at 37℃ in 5% CO2 incubator for 24 hours. Supernatant was collected for the measurement of TNF-αand IL-1β with ELISA method. Peripheral blood monocytes of seven healthy volunteers were used as control. RESULTS: The APACHE IIscore(mean±SD) of the patients at the time of blood sampling was 12.2±5.7. The primary infection foci were urinary tract infection, pneumonia, subacute bacterial endocarditis, and catheter related infection, etc. The causative organisms were gram negative rods(10 cases), gram positive cocci(6 cases) with two cases of mixed infection. Serum TNF-α could be measured in 4 cases with 29.9±27.7 pg/ml. Serum IL-1β was measureable in only one patient. The TNF-α level of supernatant of cultured peripheral blood monocytes was 2,703±2,066 pg/ml in patients and 2,102±1,914 pg/ml in controls. The IL-1β level of supernatant was 884±1,050 pg/ml in patients and 575±558 pg/ml in controls. There was no difference of TNF-α and IL-1β level between patients and controls. CONCLUSION: We cannot prove the phenomenon of endotoxin tolerance in this study. Future study needs to be focused on the more severe sepsis patients who were taken for sampling earlier. Addition of serum to the culture medium could be an another valuable option for the success of this study.

A Case of Renal Cell Carcinoma Presented with Chest Wall Metastasis / 결핵

The appearance of a tumor in the chest wall is rare compared to that in any other part of the body. It can be classified into benign and malignant types and can be located in the rib, clavicle, sternum, cartilage and soft tissues. Tumors that are metastatic are commonly located in the lung, breast, bone and pleura. But, the soft tissue mass of anterior chest wall is rarely metastasized from a distant organ that is not confined to the thoracic cavity. This and thus has rarely been described. A 68-year-old man was admitted to our hospital with a chief complaint of resting dyspnea. A huge non-tender mass of about 10*15 cm in size was visible on his left lower anterior chest wall. We pathologically confirmed that the mass was a metastatic renal cell carcinoma of clear cell type by incision biopsy. Through an incision biopsy, the mass was pathologically confirmed as a metastatic renal cell carcinoma of the clear cell type.

A Case of Endobronchial Granular Cell Tumor Associated with Malignant Mediastinal Tumor / 결핵

Granular Cell Tumors(GCT) were originally described as myoblastic myomas. Subsequent scientific investigations elucidated the origin of this tumor as Schwann cells . Usually they have a predilection for head and neck, but also can occur in many other organs. This tumor is believed to originate from Schwann cells based on subsequent scientific investigations. Although it usually appears in the head and neck, it can also appear in other organs, as well. Endobronchial granular cell tumors are rather rare and should be differentiated from other common diseases of endobronchial location endobronchial diseases such as bronchogenic carcinoma and endobronchial tuberculosis, especially in Korea . We report a A case of a patient with an extremely rare condition of endobronchial granular cell tumor concurrent with malignant mediastinal tumor in a patient (delete) is reported.

Activation of the NF-kappaB p50/p65 Complex in Human Lung Cancer Cell Lines / 결핵

BACKGROUND: NF-kappaB is a characteristic transcriptional factor whose functional activity is determined by post- translational modification of protein and subsequent change of subcellular localization. The involvement of the NF- kappaB family of the transcription factors in the control of such vital cellular functions as immune response, acute phase reaction, replication of certain viruses and development and differentiation of cells has been clearly documented in many previous studies. Several recent observations have suggested that the NF-kappaB might also be involved in the carcinogenesis of some hematological and solid tumors. Investigating the possibility that members of the NF- kappaB family participate in the molecular control of malignant cell transformation could provide invaluable information on both molecular pathogenesis and cancer-related gene therapy. METHOD: To determine the expression patterns and functional roles of NF-kappaB family transcription factors in human lung cancer cell lines NCI -H792, NCI-H709, NCI-H226 and NCI-H157 were analys ed by western blot, using their respective antibodies. The nuclear and the cytoplasmic fraction of protein extract of these cell lines were subsequently obtained and NF- kappaB expression in each fraction was again determined by western blot analysis. The type of NF-kappaB complex present in the cells was determined by immunoprecipitation. To detect the binding ability of cell- line nuclear extracts to the kappaB consensus oligonucleotide, electrophoretic mobility shift assay(EMSA) was performed. RESULTS: In the cultured human lung cancer cell lines tested, transcription factors of the NF- kappaB family, namely the p50 and p65 subunit were expressed and localized in the nuclear fraction of the cellular extract by western blot analysis and immunocytochemistry. Immunoprecipitation assay showed that in the cell, the p50 and p65 subunits made NF- kappaB complex. Finally it was shown by Electrophoretic Mobility Shift Assay(EMSA) that nuclear extracts of lung cancer cell lines are able to bind to NF-kappaB consensus DNA sequences. CONCLUSION: These data suggest that in human lung cancer cell lines the NF-kappaB p50/p65 complex might be activated, and strengthen the hypothesis that NF-kappaB family transcription factors might be involved in the carcinogenesis of human lung cancer.

A Case of Tsutsugamushi Disease Presented with Granulomatous Pleural Effusion / 감염

Tsutsugamushi disease is one of the acute febrile diseases caused by Orientia tsutsugamushi that is transmitted to human by the bite of larval-stage trombiculid mite (chigger). The clinical illness is characterized by abrupt onset of fever, headache, rashes, myalgia and eschar. Chest radiologic findings show reticulonodular infiltration, cardiomegaly, lymphadenopathy and in a minority, pleural effusion. About pleural effusion, it is supposed to be caused by tsutsugamushi disease itself in most cases and no case has been reported that the pleural effusion confirmed by pleural biopsy and revealed granulomatous lesions. We experienced a case of tsutsugamushi disease with pleural effusion which was also confirmed to granulomatous lesion by pleural biopsy. So we report this case with a brief review of literatures.

Effect of TNF-alpha Gene Transfer to Respiratory Cancer Cell Lines onSensitivity to Anticancer drugs / 결핵

BACKGROUND: Tumor necrosis factor(TNF) showed antitumor cytolytic effects on sensitive tumor cells in numerous in vivo and in vitro studies. But it could not be administered systemically to human because of severe systemic adverse effects at effective concentrations against tumor cells. Many studies showed that a high concentrations of TNF in the local milieu may evoke in vivo TNF-responsive mechanisms sufficient to suppress tumor growth. Recently developed technique of TNF gene transfer to tumor cells using retrovirus vector could be a good candidate for local TNF administration. TNF is also known to synergistically enhance in vitro cytotoxicity of chemotherapeutic drugs targeted to DNA topoisomerase II against TNF-sensitive tumor cell lines. In this study the in vitro chemosensitivity against DNA topoisomerase II targeted chemotherapeutic drugs was evaluated using some respiratory cancer cell lines to which TNF gene had been transferred. METHOD: NCI-H2058, a human mesothelioma cell line, A549, a human lung adenocarcinoma cell line and WEHI 164 cell line, a murine fibrosarcoma cell line were treated with etoposide and doxorubicin, which are typical topoisomerase II - targeted chemotherapeutic agents, at different concentration. The resultant cytotoxicity was measured by MTT assay. Then the cytotoxicity of the same chemotherapeutic agents was measured after TNF-alpha gene-transfer and the two results were compared. RESULTS: The cytotoxicity was not increased significantly in WEHI 164 cell line and A549 cell line but statistically significant increase was observed in H2058 cell line when TNF-alpha gene was transferred(p <0.05). CONCLUSION: These findings show that TNF-alpha gene transfer to respiratory cancer cell lines results in variable effects on chemosensitivity against topoisomerase II inhibitor among different cell lines in vitro and can be additively cytotoxic in certain selective tumor cell lines.

Sequential bronchoscopic findings of endobronchial tuberculosis / 결핵

No abstract available.

The role of cyclooxygenase metabolities in the pathogeneticmechanism of endotoxin-induced acute lung injury in domestic pigs / 결핵

No abstract available.

The changes of serum angiotensin converting enzyme activity in lung cancer patients / 결핵

No abstract available.

Clinical characteristics of synchronous multiple primary lung cancer / 결핵

No abstract available.

The changes of arterial oxygen saturation during sleep in chronic obstructive pulmonary disease patients / 결핵

No abstract available.

The role of reactive oxygen free radical in the pathogenetic mechan- ism of endotoxin-induced acute lung injury in domestic pigs / 결핵

No abstract available.

A case of chronic eosinophilic pneumonia after ingestion of wild rats / 결핵

No abstract available.