Chung, Mi Joo;Suh, Young Jin;Lee, Hyo Chun;Kang, Dae Gyu;Kim, Eun Joong;Kim, Sung Hwan;Lee, Jong Hoon
Radiation Oncology Journal
/
v.31
no.4
/
pp.228-233
/
2013
Purpose: The aim of this study was to evaluate changes in breast tumor bed volume during whole breast irradiation (WBI). Materials and Methods: From September 2011 to November 2012, thirty patients who underwent breast-conserving surgery (BCS) followed by WBI using computed tomography (CT) simulation were enrolled. Simulation CT scans were performed before WBI (CT1) and five weeks after the breast irradiation (CT2). The tumor bed was contoured based on surgical clips, seroma, and postoperative change. We retrospectively analyzed the factors associated with tumor bed volumetric change. Results: The median tumor bed volume on CT1 and CT2 was 29.72 and 28.6 mL, respectively. The tumor bed volume increased in 9 of 30 patients (30%) and decreased in 21 of 30 patients (70%). The median percent change in tumor bed volume between initial and boost CT was -5%. Seroma status (p = 0.010) was a significant factor in tumor bed volume reduction of 5% or greater. However, patient age, body mass index, palpability, T stage, axillary lymph node dissection, and tumor location were not significant factors for tumor bed volumetric change. Conclusion: In this study, volumetric change of tumor bed cavity was frequent. Patients with seroma after BCS had a significant volume reduction of 5% or greater in tumor bed during breast irradiation. Thus, resimulation using CT is indicated for exquisite boost treatment in breast cancer patients with seroma after surgery.
Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) gene-transduced tumor cell vaccines induce very potent systemic anti-tumor immunity in preclinical and clinical models. Our previous phase I clinical trial in patients with metastatic renal cell carcinoma (RCC) has demonstrated both immune cell infiltration at vaccine sites and T cell-mediated delayed-type hypersensitivity (DTH) response to whole tumor cell vaccines. Methods: To investigate the immune responses to autologous genetically- modified tumor cell vaccines, tumor-specific $CD8^+$ T cell lines were generated from peripheral blood lymphocytes (PBL) of a RCC patient 1.24 by repeated in vitro stimulation with either B7.1-transduced autologous RCC tumor cells or B7.1-transduced autologous tumor cells treated with interferon gamma ($IFN{\gamma}$), and cloned by limiting dilution. Results: Among several RCC-specific cytotoxic T lymphocytes (CTLs), a $CD4^+/CD8^+$ double positive T cell clone (17/A2) appeared to recognize $IFN{\gamma}$-treated autologous RCC restricted by HLA-B39. The 17/A2 also recognized other HLA-B39 positive RCC tumor cells after $IFN{\gamma}$ treatment. Conclusion: These results demonstrate that autologous RCC vaccination successfully generates the tumor-specific CTL 17/A2, and suggest that the presentation and recognition of the tumor antigen by the 17/A2 might be upregulated by $IFN{\gamma}$.
Kim, Hoonsup;Lee, Youngjoo;Lee, Songhyun;Kim, Jae Gwan
Current Optics and Photonics
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v.3
no.6
/
pp.555-565
/
2019
Development of a biomarker for predicting tumor-treatment efficacy is a matter of great concern, to reduce time, medical expense, and effort in oncology therapy. In a preclinical study, we hypothesized that the blood-flow parameter based on laser speckle flowmetry (LSF) could be a potential indicator to estimate the efficacy of breast-cancer treatment. To verify this hypothesis, a 13762-MAT-B-III rat breast tumor was grown in a dorsal skinfold window chamber applied to a nude mouse, and the change in blood flow rate (BFR) - or the speckle flow index (SFI) is used together as the same meaning in this manuscript - was longitudinally monitored during tumor growth and metronomic cyclophosphamide treatment. Based on the daily LSF angiogram, several BFR parameters (baseline SFI, normalized SFI, and △rBFR) were compared to tumor size in the normal, treated, and untreated tumor groups. Despite the incomplete tumor treatment, we found that the daily changes in all BFR parameters tended to have partially positive correlation with tumor size. Moreover, we observed that the changes in baseline SFI and normalized SFI responded one day earlier than the tumor shrinkage during chemotherapy. However, daily variations in the hypercapnia-induced △rBFR lagged tumor shrinkage by one day. This study would contribute not only to evaluating tumor vascular response to treatment, but also to monitoring blood-flow-mediated diseases (in brain, skin, and retina) by using LSF in preclinical settings.
Oxygen consumption rate $(QO_2)$ and protein content of liver and kidney of the Ehrlich ascites tumor-bearing mouse were measured from 6th till 14th day after the inoculation of $4{\times}10^6$ Ehrlich ascites tumor cells. The results thus obtained were compared with those of the groups in which; 1) Whole body x-irradiation with 400 r was done to mouse prior to the inoculation of $4{\times}10^6$ Ehrlich ascites tumor cells, 2) Same number of the irradiated tumor cells were inoculated after subjecting the tumor cells to x-irradiation with 400 r or 900 r in vitro, and 3) the normal, and the following results were obtained; 1. $QO_2$ of the liver and kidney of the tumor-bearing mouse were all lower than the normal and a gradual decrease of $QO_2$ in both liver and kidney was noted as the ascites tumor was progressively developing. 2. In the groups where whole body x-irradiation with 400 r was done, or x-irradiation of ascites tumor cells in vitro with either 400 r or 900 r, $QO_2$ of the liver and kidney were lower than the normal, and the pattern of the decrease was similar in the case of the tumor-bearing mouse. 3. Protein contents in all the groups showed lower values than the normal, and the decrease was gradual as the ascites tumor was developing. 4. $QO_2$ and protein levels in the liver were generally lower than those in the kidney. 5. A certain cancerous metabolism was, therefore, noted in the remote organs of Ehrlich ascites tumor-bearing animal.
This study was carried out to find new anti-tumor agent producing microbe and to characterize the anti-tumor agent produced from the microbe. Purified compound that has a high cytotoxicity against tumor cell-lines could be obtained from the broth culture filtrates of Streptomyces sp.409 strain isolated from soil in Korea. The in vitro cytotoxicity the in vivo evaluation of acute toxicity the safety assessment of the anti-tumor compounds and the taxonomic characteristics of the anti-tumor agent were measured. The antitumor compound 1 and 2 were obtained from the broth culture filtrates of Streptomyces sp.409 strain. The cytotoxicity of the compound 1 against tumor cell-line P388D$_1$ showed almost 4.5 times higher than that of adriamycin. However in the cytotoxicity against normal cell line Vero E6, adriamycin showed adversely 4 times higher than the compound 1 ($IC_{50}$/ value: 228.7 $\mu\textrm{g}$/$m\ell$). In comparison study with compound 1 and compound 2 in the in vitro cytotoxin productivity against tumor cell lines, $IC_{50}$/ value of the compound 1 was 0.25 $\mu\textrm{g}$/$m\ell$ in tumor cell line P388D$_1$and 0.53 $\mu\textrm{g}$/$m\ell$ in tumor cell-line L1210, and that of the compound 2 was 7.18 $\mu\textrm{g}$/$m\ell$ and 35.71 $\mu\textrm{g}$/$m\ell$, respectively; LD$_{50}$ value of the compound 1 in the in vivo acute toxicity in mice was 22.62 $\mu\textrm{g}$/kg body weight. These results suggest that compound 1 purified from Streptomyces sp. 409 has anti-tumor activity and will be developed as an anti-tumor drug.g.
Rhee, S.K.;Kim, J.M.;Kim, H.M.;Kang, Y.K.;Kim, Y.S.;Kwon, S.Y.;Lee, K.T.;Kim, I.
The Journal of the Korean bone and joint tumor society
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v.1
no.2
/
pp.205-209
/
1995
A desmoid tumor is a locally aggressive growth of connective tissue origin which infiltrates the surrounding tissue and has a marked tendency for recurrence. And so it was also called as an aggressive fibromatosis, musculofascial fibromatosis or fibrosarcoma etc. Thirteen cases of desmoid tumor was treated since 1980, and their retrospective study was done with 79 months of follow-up after initial surgical excision. The female was involved in 12 cases(one male) with the age ranged from 7-50 years, average 28 years, and seven patients in third decade. A slowly growing mass was excised on average 4 months after first notice of the mass, but their margins are not demarcated clearly in most cases. Wide excision in 12 cases was done, but wide excision and saphenous vein graft was performed in one case because of invasion of posterior tibial artery by tumor mass. The tumor was found on extraabdominal region in 8 cases(61.5%) but 5 cases in abdominal wall(38.5%). The recurrence rate was high(6/13, 46.2%), and 11 times in 6 patients were recurred(average 1.8 times), within 27 months of initial excision. Six cases of recurrence were treated with wide excision again in 3 cases, wide excision combined with radiotherapy(4,000-6,000cGy) in 4 cases and wide excision with chemotherapy in one case. During the follow-up for average 21 months after treatment, no recurrences are found. Tumor remission periods without recurrence are average 67 months in all, and 11 years in longest case. Histologically it was very mimic with fibrosarcoma but could be differentiated with Trichrome stain, and their findings are not changed after recurrence.
Background: Immunization of dendritic cells (DCs) pulsed with tumor antigen can activate tumor-specific cytotoxic T lymphocytes (CTL) that are responsible for protection and regression. In this study, we examined whether the uptake of necrotic tumor cells could modulate DC phenotypes and whether the immunization of necrotic tumor cell-loaded DCs could elicit efficient tumor specific immune responses followed by a regression of established tumor burdens. Methods: We prepared necrotic tumor cell-pulsed DCs for the therapeutic vaccination and investigated their phenotypic characteristics, the immune responses induced by these DCs, and therapeutic vaccine efficacy against colon carcinoma in vivo. Several parameters including phagocytosis of tumor cells, surface antigen expression, chemokine receptor expression, IL-12 production, and NK as well as CTL activation were assessed to characterize the immune response. Results: DCs derived from mouse bone marrow efficiently phagocytosed necrotic tumor cells and after the uptake, they produced remarkably increased levels of IL-12. A decreased CCR1 and increased CCR7 expression on DCs was also observed after the tumor uptake, suggesting that antigen uptake could induce DC maturation. Furthermore, co-culturing of DCs with NK cells in vitro enhanced IL-12 production in DCs and IFN-${\gamma}$ production in NK cells, which was significantly dependent on IL-12 production and cell-to-cell contact. Immunization of necrotic tumor cell-loaded DCs induced cytotoxic T lymphocytes as well as NK activation, and protected mice against subsequent tumor challenge. In addition, intratumoral or contra-lateral immunization of these DCs not only inhibited the growth of established tumors, but also eradicated tumors in more than 60% of tumor-bearing mice. Conclusion: Our data indicate that production of IL-12, chemokine receptor expression and NK as well as CTL activation may serve as major parameters in assessing the effect of tumor cell-pulsed DC vaccine. Therefore, DCs loaded with necrotic tumor cells offer a rational strategy to treat tumors and eventually lead to prolonged survival.
Rhee, Jong Joo;Ahn, Jae Sung;Jeon, Sang Ryong;Kim, Jeong Hoon;Ra, Young Shin;Kim, Chang Jin;Lee, Jung Kyo;Kwun, Byung Duk
Journal of Korean Neurosurgical Society
/
v.30
no.sup2
/
pp.221-227
/
2001
Objective : The therapeutic impact of tumor resection in glioblastomas is poorly defined and still questionable. Therefore, we conducted the current study to verify the role of tumor resection in the treatment of these highly malignant tumors. Methods : A retrospective study was performed(1990-1999) to compare the treatment results of surgical resection plus radiotherapy(130 patients) with those of stereotactic biopsy plus radiotherapy(19 patients) in glioblastomas. Only adult patients with supratentorial, de novo glioblastoma located in one lobe were included. Survival time/rate was analysed with Kaplan-Meier method, and prognostic variables were obtained from the univariate log-rank test and the multivariate Cox's proportional hazards model. Results : The resection group and the biopsy group did not differ in terms of age, gender, duration of symptoms, presenting symptoms, tumor location, tumor side, tumor size, and the frequency of midline shift. Patients in the biopsy group more often were found to have worse preoperative Karnofsky performance status(KPS)(p=0.001). On univariate analysis, age, KPS, and tumor side were associated with survival(p=0.0053, 0.0001, and 0.0331 respectively). Median survival time and 1-year survival rate were also statistically improved by tumor resection ; resection group - 13 months and 61.2%, and biopsy group - 8 months and 19.7%, respectively(p=0.0001). In patients with midline shift of the tumor, resection was highly effective comparing to biopsy(p=0.0001), but in patients without midline shift, external beam radiation alone was as effective as tumor resection(p=0.0605). Other prognostic variables did not affect survival. On multivariate analysis after variable selection, survival was independently associated with KPS(p=0.001), but not the surgical resection(p=0.2837). Even in biopsy group with midline shift of the tumor, survival rate was not different from that seen after tumor resection(p=0.3505). Conclusions : Radiotherapy alone was as effective as tumor resection plus radiotherapy in patients without midline shift of the tumor. Although there was not statistically significant, tumor resection looked like effective in patients with midline shift. For supratentorial, lobar glioblastoma patients without mass effect of the tumor, biopsy with radiotherapy is one of rational treatment strategies. We consider that tumor resection should be performed in patients with pretreatment midline shift.
Park, Hae-Young;Wakefield, Lalage M;Mamura, Mizuko
IMMUNE NETWORK
/
v.9
no.4
/
pp.122-126
/
2009
Transforming growth factor-$\beta$ (TGF-$\beta$) is a highly pleiotropic cytokine playing pivotal roles in immune regulation. TGF-$\beta$ facilitates tumor cell survival and metastasis by targeting multiple cellular components. Focusing on its immunosuppressive functions, TGF-$\beta$ antagonists have been employed for cancer treatment to enhance tumor immunity. TGF-$\beta$ antagonists exert anti-tumor effects through #1 activating effector cells such as NK cells and cytotoxic $CD8^+$ Tcells (CTLs), #2 inhibiting regulatory/suppressor cell populations, #3 making tumor cells visible to immune cells, #4 inhibiting the production of tumor growth factors. This review focuses on the effect of TGF-$\beta$ on T cells, which are differentiated into effector T cells or newly identified tumor-supporting T cells.
Two cases of pulmonary atypical carcinoid tumor were diagnosed by fine needle aspiration cytology. Although the cytologic features of atypical carcinoid tumor have been relatively well described, it is easy to confuse atypical carcinoid tumor with typical carcinoid tumor, small cell carcinoma and adenocarcinoma of the lung. Atypical carcinoid tumor has been recognized as a distinct variant of pulmonary neuroendocrine carcinoma, with characteristic histopathologic and clinical features that separate it from both carcinoid and small cell carelnoma. The distinction of atypical carcinoid tumor from small cell carcinoma has important prognostic and therapeutic implications. The cytologic characteristics of atypical carcinoid tumor included polygonal to fusiform cells with a variable amount of lacy cytoplasm, oval nuclei with coarsely dispersed chromatin and frequent nucleoli, and mild pleomorphism. The malignant cells were arranged either in acinus-like clusterg or in epithelial sheets.
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