• IMMUNE NETWORK
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• v.21 no.3
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• pp.23.1-23.16
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• 2021

Chemokines are key factors that influence the migration and maintenance of relevant immune cells into an infected tissue or a tumor microenvironment. Therefore, it is believed that the controlled administration of chemokines in the tumor microenvironment may be an effective immunotherapy against cancer. Previous studies have shown that CCL3, also known as macrophage inflammatory protein 1-alpha, facilitates the recruitment of dendritic cells (DCs) for the presentation of tumor Ags and promotes T cell activation. Here, we investigated the role of CCL3 in regulating the tumor microenvironment using a syngeneic mouse tumor model. We observed that MC38 tumors overexpressing CCL3 (CCL3-OE) showed rapid regression compared with the wild type MC38 tumors. Additionally, these CCL3-OE tumors showed an increase in the proliferative and functional tumor-infiltrating T cells. Furthermore, PD-1 immune checkpoint blockade accelerated tumor regression in the CCL3-OE tumor microenvironment. Next, we generated a modified CCL3 protein for pre-clinical use by fusing recombinant CCL3 (rCCL3) with a non-cytolytic hybrid Fc (HyFc). Administering a controlled dose of rCCL3-HyFc via subcutaneous injections near tumors was effective in tumor regression and improved survival along with activated myeloid cells and augmented T cell responses. Furthermore, combination therapy of rCCL3-HyFc with PD-1 blockade exhibited prominent effect to tumor regression. Collectively, our findings demonstrate that appropriate concentrations of CCL3 in the tumor microenvironment would be an effective adjuvant to promote anti-tumor immune responses, and suggest that administering a long-lasting form of CCL3 in combination with PD-1 blockers can have clinical applications in cancer immunotherapy.

• Asian-Australasian Journal of Animal Sciences
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• v.22 no.10
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• pp.1359-1365
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• 2009

We performed a genome-wide linkage and quantitative trait locus (QTL) analysis to confirm the existence of QTL affecting Rous Sarcoma Virus (RSV) induced tumor regression, and to estimate their effects on phenotypic variance in an F2 resource population. The F2 population comprised 158 chickens obtained by crossing tumor regressive White Leghorn (WL) and tumor progressive Rhode Island Red (RIR) lines was measured for tumor formation after RSV inoculation. Forty-three tumor progressive and 28 tumor regressive chickens were then used for genome-wide linkage and QTL analysis using a total of 186 microsatellite markers. Microsatellite markers were mapped on 20 autosomal chromosomes. A significant QTL was detected with marker LEI0258 located within the MHC B region on chromosome 16. This QTL had the highest F ratio (9.8) and accounted for 20.1% of the phenotypic variation. Suggestive QTL were also detected on chromosomes 4, 7 and 10. The QTL on chromosome 4 were detected at the 1% chromosome-wide level explaining 17.5% of the phenotypic variation, and the QTLs on chromosome 7 and 10 were detected at the 5% chromosome-wide level and explained 11.1% and 10.5% of the phenotypic variation, respectively. These results indicate that the QTLs in the non-MHC regions play a significant role in RSV-induced tumor regression. The present study constitutes one of the first preliminary reports in domestic chickens for QTLs affecting RSV-induced tumor regression outside the MHC region.

• Radiation Oncology Journal
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• v.34 no.3
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• pp.186-192
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• 2016

Purpose: To determine whether large rectal volume on planning computed tomography (CT) results in lower tumor regression grade (TRG) after neoadjuvant concurrent chemoradiotherapy (CCRT) in rectal cancer patients. Materials and Methods: We reviewed medical records of 113 patients treated with surgery following neoadjuvant CCRT for rectal cancer between January and December 2012. Rectal volume was contoured on axial images in which gross tumor volume was included. Average axial rectal area (ARA) was defined as rectal volume divided by longitudinal tumor length. The impact of rectal volume and ARA on TRG was assessed. Results: Average rectal volume and ARA were 11.3 mL and $2.9cm^2$. After completion of neoadjuvant CCRT in 113 patients, pathologic results revealed total regression (TRG 4) in 28 patients (25%), good regression (TRG 3) in 25 patients (22%), moderate regression (TRG 2) in 34 patients (30%), minor regression (TRG 1) in 24 patients (21%), and no regression (TRG0) in 2 patients (2%). No difference of rectal volume and ARA was found between each TRG groups. Linear correlation existed between rectal volume and TRG (p = 0.036) but not between ARA and TRG (p = 0.058). Conclusion: Rectal volume on planning CT has no significance on TRG in patients receiving neoadjuvant CCRT for rectal cancer. These results indicate that maintaining minimal rectal volume before each treatment may not be necessary.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.6
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• pp.3881-3885
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• 2013

Objective: The objective of this study was to identify clinical predictive factors for tumor response after neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC). Methods: All factors were evaluated in 88 patients with LARC treated with nCRT. After a long period of 4-8 weeks of chemoradiotherapy, 3 patients achieved clinical complete response (cCR) and thus aggressive surgery was avoided, and the remaining 85 patients underwent a curative-intent operation. The response to nCRT was evaluated by tumor regression grade (TRG) system. Results: There were 32 patients (36.4%) with good tumor regression (TRG 3-4) and 56 (63.6%) with poor tumor regression (TRG 0-2). Lymphocyte counts and ratios were higher in good response cases (P=0.01, 0.03, respectively) while neutrophil ratios and N/L ratios were higher in poor response cases (P=0.04, 0.02, respectively). High lymphocyte ratios before nCRT and good tumor regression (TRG3-4) were significantly associated with improved 5-year disease-free survival (P<0.05). Pretreatment nodal status was also significantly associated with 5-year disease-free survival and 5-year overall survival (P<0.05). Multivariate analysis confirmed that the pretreatment lymphocyte ratio and lymph nodal status were independent prognostic factors. Conclusion: Our study suggested that LARC patients with high lymphocyte ratios before nCRT would have good tumor response and high 5-year DFS and OS.

• The Journal of the Korean bone and joint tumor society
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• v.10 no.1
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• pp.39-44
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• 2004

A Giant cell tumor of bone has unusual characteristics of pulmonary metastasis as well as local aggressiveness. Clinical courses of pulmonary metastasis of benign giant cell tumor vary including rapid growth, continuously slow growth or spontaneous regression. We report a case of extensive pulmonary metastasis of giant cell tumor of bone, which regressed spontaneouly.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.19
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• pp.8149-8153
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• 2014

Background: To compare the value of contrast-enhanced ultrasound (CEUS) qualitative and quantitative analysis in the identification of breast tumor lumps. Materials and Methods: Qualitative and quantitative indicators of CEUS for 73 cases of breast tumor lumps were retrospectively analyzed by univariate and multivariate approaches. Logistic regression was applied and ROC curves were drawn for evaluation and comparison. Results: The CEUS qualitative indicator-generated regression equation contained three indicators, namely enhanced homogeneity, diameter line expansion and peak intensity grading, which demonstrated prediction accuracy for benign and malignant breast tumor lumps of 91.8%; the quantitative indicator-generated regression equation only contained one indicator, namely the relative peak intensity, and its prediction accuracy was 61.5%. The corresponding areas under the ROC curve for qualitative and quantitative analyses were 91.3% and 75.7%, respectively, which exhibited a statistically significant difference by the Z test (P<0.05). Conclusions: The ability of CEUS qualitative analysis to identify breast tumor lumps is better than with quantitative analysis.

• Annals of Surgical Treatment and Research
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• v.96 no.2
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• pp.78-85
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• 2019

Purpose: Insistence that total regression of primary tumor would not represent long-term oncologic outcomes has been raised. Therefore, this study aimed to evaluate the outcomes of these patients after preoperative chemoradiotherapy (PCRT) and radical surgery and to evaluate the associated risk factors. Methods: We included 189 patients with rectal cancer who showed total regression of the primary tumor after PCRT, followed by radical resection, between 2001 and 2012. Recurrence-free survival (RFS) was calculated using the Kaplan-Meier method, and the results were compared with 77 patients with Tis rectal cancer who received only radical resection. Factors associated with RFS were evaluated using Cox regression analysis. Results: Sphincter-saving resection was performed for 146 patients (77.2%). Adjuvant chemotherapy was administered to 168 patients (88.9%). During the follow-up period, recurrence occurred in 17 patients (9%). The 5-year RFS was 91.3%, which was significantly lower than that of patients with Tis rectal cancer without PCRT (P = 0.005). In univariate analysis, preoperative CEA and histologic differentiation were associated with RFS. However, no factors were found to be associated with RFS. Conclusion: RFS was lower in patients with total regression of primary rectal cancer after PCRT than in those with Tis rectal cancer without PCRT, and it would not be considered as the same entity with early rectal cancer or "disappeared tumor" status.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.17
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• pp.7463-7466
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• 2015

Aims: To analyse the predictors of recurrence, disease free survival and overall survival in cases with endometrial cancer. Materials and Methods: A total of 152 women diagnosed with endometrial cancer were screened using a prospectively collected database including age, smoking history, menopausal status, body mass index, CA125, systemic disorders, tumor histology, tumor grade, lymphovascular space invasion, tumor diameter, cervical involvement, myometrial invasion, adnexal metastases, positive cytology, serosal involvement, other pelvic metastases, type of surgery, fertility sparing approach to assess their ability to predict recurrence, disease free survival and overall survival. Results: In ROC analyses tumor diameter was a significant predictor of recurrence (AUC:0.771, P<0.001). The optimal cut off value was 3.75 with 82% sensitivity and 63% specificity. In correlation analyses tumor grade (r=0.267, p=0.001), tumor diameter (r=0.297, p<0.001) and the serosal involvement (r=0.464, p<0.001) were found to significantly correlate with the recurrence. In Cox regression analyses when some different combinations of variables included in the model which are found to be significantly associated with the presence of recurrence, tumor diameter was found to be a significant confounder for disease free survival (OR=1.2(95 CI,1.016-1.394, P=0.031). On Cox regression for overall survival only serosal involvement was found to be a significant predictor (OR=20.8 (95 % CI 2.4-179.2, P=0.006). In univariate analysis of tumor diameter > 3.75 cm and the recurrence, there was 14 (21.9 %) cases with recurrence in group with high tumor diameter where as only 3 (3.4 %) cases group with smaller tumor size (Odds ratio:7.9 (95 %CI 2.2-28.9, p<0.001). Conclusions: Although most of the significantly correlated variables are part of the FIGO staging, tumor diameter was also found to be predictor for recurrence with higher values than generally accepted.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.6
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• pp.2639-2642
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• 2012

Background: The patterns of gastric cancer recurrence vary across societies. We designed the current study in an attempt to evaluate and reveal the outbreak of the recurrence patterns of gastric cancer and also prediction of time to recurrence and its effected factors in Iran. Materials and Methods: This research was performed from March 2003 to February 2007. Demographic characteristics, clinical and pathological diagnosis and classification including pathologic stage, tumor grade, tumor site and tumor size in of patients with GC recurrent were collected from patients' data files. To evaluate of factors affected on the relapse of the GC patients, gender, age at diagnosis, treatment type and Hgb were included in the research. Data were analyzed using Kaplan-Meier and logistic regression models. Results: After treatment, 82 patients suffered recurrence, 42, 33 and 17 by the ends of first, second and third years. The mean ( SD) and median ( IQR) time to recurrence in patients with GC were 25.5 (20.6-30.1) and 21.5 (15.6-27.1) months, respectively. The results of multivariate analysis logistic regression showed that only pathologic stage, tumor grade and tumor site significantly affected the recurrence. Conclusions: We found that pathologic stage, tumor grade and tumor site significantly affect on the recurrence of GC which has a high positive prognostic value and might be functional for better follow-up and selecting the patients at risk. We also showed time to recurrence to be an important factor for follow-up of patients.

• Radiation Oncology Journal
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• v.6 no.2
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• pp.295-300
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• 1988

Chordoma is a malignant tumor arising from the primitive notochord involving the axial skeleton. It usually occurs at sacrococcygeal and besisphenoidal area but only rarely does at other vertebral areas, especially at the thoracic vertebrae. It has a slow growth rate and is locally aggressive with an extremely high rate of local recurrence. Either surgery or radiation alone often fails to cure the disease and the local failure is the main cause of treatment failure and death. Overall 5 year survival rate is less than $10\%$. Useful palliation or occasional cure can be obtained by the combination of surgery and radiotherapy. After incomplete resection, the tumor requires radiation dose of 7,000 cGy or more over 6-7 weeks for local control. Tumor regression is slow in response to irradiation and continuation of the regression for several months after completion of RT is not unusual. We report a case of chordoma of the thoracic vertebra, the site of extreme rarity, which showed good local control after partial resection and radiation therapy. He is well and alive without any evidence of recurrence after 13 months of treatment with near complete tumor regression.