• 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.

• Tuberculosis and Respiratory Diseases
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• v.42 no.4
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• pp.502-512
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• 1995

Background: One quarter to one third of patients with NSCLC present with primary tumors that although confined to the thorax are too extensive for surgical resection. Until resently standard treatment for these patients had been thoracic radiation, which produces tumor regression in most patients but few cures and dismal 5-year survival rate. The fact that death for most patients with stage III tumors is caused by distant metastases has promped a reevaluation of combined modality treatment approaches that include systemic chemotherapy. Therefore, we report the results observed in a study to evaluate the effect of multimodality treatment in locally advanced non-small cell lung cancer from 1/91 to 8/93 in CNUH. Method: We grouped the patients according to the treatment modalities and evaluated response rate, median survival and the effect of prognostic variables. Among 67 patients evaluated, twenty seven patients classified with group A, received cisplatin and etoposide containing combination chemotherapy alone, eighteen patients, classified with group B, received chemotherapy and radiotherapy, fifteen patients, group C, received neoadjuvant or adjuvant chemotherapy and surgery with/without radiation therapy, seven patients, group D, received only supportive care. Result: The major response rate for group A and B was 37% and 61% respectively. There was no statistically significant difference in response rate between A and B groups(p=0.97). The analysis of prognostic factors showed that differences of age, sex, pathology, blood type, smoking year, stage and ECOG performance did not related to improvement in survival. Median survival time was 8.6 months for group A, 13.4 months for group B, 19.2 months for group C, and 5.4 months for group D, respectively and there was statistically significant difference(p=0.003), suggesting that multimodality therapy was associated with signigicant improvement in survival. Subset survival analysis showed a significant therapeutic effect for earlier stage and good performance state(p=0.007, 0.009, respectively). A possible survival advantages were observed for major response groups. Conclusion: It was suggested that multimodality therapy for the management of patients who had stage III disease, has yielded good median survival and long survival for seleted patients. But, it is necessory to validate above result with further investigation in large scale and in prospective randomized trials.

• Journal of The Korean Society of Clinical Toxicology
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• v.15 no.1
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• pp.11-16
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• 2017

Purpose: The association of hypoalbuminemia with 30-day in-hospital mortality in patients with organophosphate insecticide poisoning (OPI) was studied. Methods: This retrospective cohort study was conducted between January 2006 and November 2013 in the emergency department (ED) after OPI poisoning. A Kaplan-Meier 30-day survival curve and the log-rank test were used to analyze patients stratified according to serum albumin levels on ED admission (hypoalbuminemia or normo-albuminemia). Independent risk factors including hypoalbuminemia for 30-day mortality were determined by multivariate Cox regression analysis. Results: A total of 135 patients were included. Eighty-eight (65%) patients were male and the mean age was $57.3{\pm}17.0$ years. Serum albumin, mean arterial pressure, and Glasgow coma scale score were significantly higher in the survival group than the non-survival group. APACHE II score was significantly lower in the non-survival group than the survival group. The mortality of the hypoalbuminemia group (serum albumin <3.5 g/dl) was 68.8%, while that of the normo-albuminemia group (serum albumin ${\geq}3.5g/dl$) was 15.1%. The area under the ROC curve of the serum albumin level was 0.786 (95% CI, 0.690-0.881) and the APACHE II score was 0.840 (95% CI, 0.770-0.910). Conclusion: Hypoalbuminemia is associated with 30-day mortality in patients with OPI poisoning.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.6
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• pp.2431-2440
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• 2015

Background: Registry data from four major public hospitals indicate trends in clinical care and survival from colorectal cancer over three decades, from 1980 to 2010. Materials and Methods: Kaplan-Meier productlimit estimates and Cox proportional hazards models were used to investigate disease-specific survival and multiple logistic regression analyses to explore first-round treatment trends. Results: Five-year survivals increased from 48% for 1980-1986 to 63% for 2005-2010 diagnoses. Survival increases applied to each ACPS stage (Australian Clinico-Pathological Stage), and particularly stage C (an increase from 38% to 68%). Risk of death from colorectal cancer halved (hazards ratio: 0.50 (0.45, 0.56)) over the study period after adjusting for age, sex, stage, differentiation, primary sub-site, health administrative region, and measures of socioeconomic status and geographic remoteness. Decreases in stage were not observed. Survivals did not vary by sex or place of residence, suggesting reasonable equity in service access and outcomes. Of staged cases, 91% were treated surgically with lower surgical rates for older ages and more advanced stage. Proportions of surgical cases having adjuvant therapy during primary courses of treatment increased for all stages and were highest for stage C (an increase from 5% in 1980-1986 to 63% for 2005-2010). Radiotherapy was more common for rectal than colonic cases. Proportions of rectal cases receiving radiotherapy increased, particularly for stage C where the increase was from 8% in 1980-1986 to 60% in 2005-2010. The percentage of stage C colorectal cases less than 70 years of age having systemic therapy as part of their first treatment round increased from 3% in 1980-1986 to 81% by 1995-2010. Based on survey data on uptake of adjuvant therapy among those offered this care, it is likely that all these younger patients were offered systemic treatment. Conclusions: We conclude that pronounced increases in survivals from colorectal cancer have occurred at major public hospitals in South Australia due to increases in stage-specific survivals. Use of adjuvant therapies has increased and the patterns of change accord with clinical guideline recommendations. Reasons for sub-optimal use of radiotherapy for rectal cases warrant further investigation, including the potential for limited rural access to impede uptake of treatments at metropolitan-based radiotherapy centres.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2833-2838
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• 2015

Background: Repeating a prior chemotherapy (rechallenge therapy) is an option for selected patients with metastatic colorectal cancer, but there is very little evidence in the literature for this approach. Thus, we reviewed our registry to evaluate prognostic factors and survival of patients who received irinotecan and oxaliplatin-based regimens as rechallenge third and fourth-line therapy. Materials and Methods: Patients who received irinotecan-based or oxaliplatin-base regimen as first-line had been rechallenged with third-line or fourth-line therapy. These patients were selected from the database of Turkish mCRC registry archives between October 2006 and June 2013 and evaluated retrospectively for factors effecting progression free survival (PFS) and overall survival (OS) by the Kaplan-Meire and Cox-regression methods. Results: Thirty-nine patients were enrolled. The median duration of follow-up was 36 months (14-68 months). Thirty-one patients (76%) died during follow-up. In terms of rechallenge treatments, 29 patients had received third-line and 10 patients had received fourth-line. Response rate (RR) was found to be 12.9%, with stable disease in 19 (48.7%) patients. The median PFS was 6 months (95%CI=4.64-7.35 months) and the median OS was 11 months (95%CI=8.31-13.68 months). The factors effecting survival (PFS and OS) were only being PFS after first-line chemotherapy ${\geq}12months$ (p=0.007, 95% CI=1.75-35.22 and p=0.004, 95%CI=1.44-7.11), both in univariate and multivariate analyses. Conclusions: This study indicates that rechallenge treatment could be a good option as a third or later line therapy in patients who had ${\geq}12months$ PFS onreceiving first line therapy.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.13
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• pp.5331-5336
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• 2014

Background: Early onset breast cancer is associated with poor outcomes but variable results have been reported. It is a significant problem in Pakistani women but remains under reported. Breast conservation plays an important role in surgical management of this younger patient group. The objective of this study was to determine the outcome of breast conservative therapy in patients with early onset breast cancer in our population and compare it with their older counterparts. Materials and Methods: A review of patients with invasive breast cancer who underwent breast conservation surgery at Shaukat Khanum Cancer Hospital from 1997 to 2009 was performed. Patients were divided into two groups i.e. Group I age ${\leq}40$ and Group II >40 years. A total of 401 patients with breast cancer were identified in Group I and 405 patients in Group II. Demographics, histopathological findings and receptor status of the two groups were compared. The Chi square test was used for categorical variables. Outcome was assessed on basis of 10 year locoregional recurrence free survival (LRRFS), disease free survival (DFS) and overall survival (OS). For survival analysis Kaplan Meier curves were used and significance was determined using the Log rank test. Cox regression was applied for multivariate analysis. Results: Median follow up was 4.31 (0.1-15.5) years. Median age at presentation was 34.6 years (17-40) and 51.9 years (41-82) for the two groups. Groups were significantly different from each other with respect to grade, receptor status, tumor stage and use of neoadjuvant therapy. No significant difference was present between the two groups for estimated 10 year LRRFS (86% vs 95%) (p=0.1), DFS (70% vs 70%) (p=0.5) and OS (75% vs 63%) (p=0.1). On multivariate analysis, tumor stage was an independent predictor of LRRFS, DFS and OS. Conclusions: Early onset breast cancer is associated with a distinct biology but does not lead to poorer outcomes in our population.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.4
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• pp.1759-1767
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• 2016

Background: Uterine sarcoma is a group of rare gynecologic tumors with various natures, and different lines of treatment. Most have a poor treatment outcome. This study targeted clinical characteristics, treatment, overall survival (OS), progression-free survival (PFS), and prognostic factors in uterine sarcoma patients in one tertiary center for cancer care. Materials and Methods: Uterine sarcoma patients who were treated at the Department of Obstetrics and Gynecology, Faculty of Medicine Vajira Hospital between January 1994 and December 2014 were identified. Clinico-pathological data were analyzed. Prognostic outcomes were examined by Kaplan-Meier curves and Cox regression analysis. Results: We identified 46 uterine sarcoma patients: 25 carcinosarcoma (CS) (54.3%), 15 leiomyosarcoma (LMS) (32.6%), and 6 undifferentiated uterine sarcoma (UUS) (13.1%) cases. Mean age was $54.0{\pm}11.9years$ (range 25-82 years). Abnormal uterine bleeding was the most common presenting symptom (63.0%). Among 33 patients (71.7%) who had pre-operative tissue collected, diagnosis of malignancy was correct in 29 (87.9%). All patients received primary surgery and retroperitoneal lymph nodes were resected in 34 (73.9%). After surgery, 5 (10.9%) had gross residual tumors. Stage I disease was most commonly found (56.5%). Adjuvant treatment was given to 27 (58.7%), most commonly chemotherapy. After a median follow-up of 16.0 months (range 0.8-187.4 months), recurrence was encountered in 22 patients (47.8%). Median time to recurrence was 5.8 months (range1.0-105.5 months). Distant metastasis was more common than local or locoregional failure. The 2-year PFS was 45.2% (95% confidence interval [CI], 30.6%-59.7%) and the 2-year OS was 48.3% (95% CI, 33.3%-60.7%). Multivariable analyses found residual disease after surgery as a significant factor only for PFS. Conclusions: Uterine sarcoma is a rare tumor entity. Even with multimodalities of treatment, the prognosis is still poor. Successful cytoreductive surgery is a key factor for a good survival outcome.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.10
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• pp.4363-4368
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• 2015

Background: The tumor-stroma ratio (TSR) represents the percentage of neoplastic cell components compared to the combined area of neoplastic cells and the surrounding tumor-induced stroma. A low TSR (predomination of stromal component) has been demonstrated to be an independent adverse prognostic factor in cancers of several organs. In cervical carcinoma patients, TSR has been evaluated in only one previous study with different histological types. The present study aimed to assess the prognostic value of TSR in early stage cervical cancer patients with adenocarcinoma histology only. Materials and Methods: Histological slides of patients with early stage (IB-IIA) cervical adenocarcinoma who underwent surgical treatment between January 2003 and December 2011 were reviewed. Patients who had received preoperative chemotherapy were excluded. TSR was categorized as low (<50%) and high (${\geq}50%$). Correlations between TSR and clinicopathological variables were evaluated. Prognostic values of TSR and other variables were estimated using Cox's regression. Results: Of 131 patients; 38 (29.0%) had low TSR and 93 (71.0%) had high TSR. The patients with low TSR had significantly higher proportions of deep cervical stromal invasion (outer third of wall, p=0.011; residual stroma less than 3 mm, p=0.008) and parametrial involvement (p=0.026). Compared to the patients with high TSR, those with low TSR tended to have lower 5-year disease-free survival rate (83.8% versus 88.9%) and overall survival rate (85.6% versus 90.3%), although the differences were not statistically significant. Low TSR was significantly associated with decreased overall survival in univariate analysis (HR 2.7; 95% CI 1.0-7.0; p=0.041), but not in multivariate analysis. TSR was not significantly associated with decreased disease-free survival. Conclusions: Low TSR is associated with decreased overall survival in patients with early stage cervical adenocarcinoma treated by surgery. However, it was not found to be an independent prognostic predictor in this study.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.5
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• pp.2101-2107
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• 2012

Treatment responses of $N_0$ stage nasopharyngeal carcinoma were firstly analyzed comprehensively to evaluate long term outcomes of patients and identify prognostic factors. A total of 610 patients with $N_0$ NPC, undergoing definitive radiotherapy to their primary lesion and prophylactic radiation to upper neck, were reviewed retrospectively. Concomitant chemotherapy was administrated to 65 out of the 610. Survival rates of the patients were calculated using the Kaplan-Meier method and compared by log-rank test. Prognostic factors were identified by the Cox regression model. The study revealed the 5-year and 10-year overall, disease-free, disease-specific, local failure-free, regional failure-free, locoregional failure-free and distant metastasis-free survival rates to be 78.7% and 66.8%, 68.8% and 55.8%, 79.9% and 70.4%, 81.2% and 72.5%, 95.8% and 91.8%, 78.3% and 68.5%, 88.5% and 85.5%, respectively. There were 192 patients experiencing failure (31.5%) after radiotherapy or chemoradiotherapy. Of these, local recurrence, regional relapse and distant metastases as the first event of failure occurred in 100 (100/610, 16.4%), 15(15/610, 2.5%) and 52 (52/610, 8.5%), respectively. Multivariate analysis showed that T stage was the only independent prognostic factor for patients with $N_0$ NPC (P=0.000). Late T stage (P=0.000), male (P=0.039) and anemia (P=0.007) were independently unfavorable factors predicting disease-free survival. After treatment, satisfactory outcome wasgenerally achieved in patients with $N_0$ NPC. Local recurrence represented the predominant mode of treatment failure, while T stage was the only independent prognostic factor for overall survival. Late T stage, male gender, and anemia independently predicted lower possibility of the disease-free survival.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.3
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• pp.827-831
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• 2012

To determine the relationship between comorbidity and outcome after radical cystectomy in Chinese patients by using the Adult Comorbidity Evaluation (ACE)-27 index. Two-hundred-and-forty-six patients treated with radical cystectomy at the Second Xiangya Hospital of Central South University, Hunan Province, China between 2000 and 2010 were retrospectively analyzed. Medical records were reviewed for age, gender, delayed time of radical cystectomy, urinary diversion type, pelvic lymphadenectomy status, TNM stage, and pathological grade. Comorbidity information was assessed by the ACE-27 index. The outcome measurement was overall survival. Univariate and multivariate Cox proportional hazards regression analyses were used to determine the association between comorbidity and outcome. The study population consisted of 215 (87.40%) males and 31 (12.60%) females with a mean age of $62{\pm}11$ years. Median duration of follow-up was $47{\pm}31$ months. A total of 151 (61.38%) patents died during follow-up. Of those, 118 (47.97%) had at least one comorbidity. According to the ACE-27 scores, 128 (52.03%) patients had no comorbidity, 79 (32.11%) had mild, 33 (13.41%) had moderate, and 6 (2.45%) had severe comorbidities. Multivariate analysis indicated that moderate (p=0.002) and severe (p<0.001) comorbidity was significantly associated with decreased overall survival. In addition, age ${\geq}70$ years (p=0.002), delayed time of radical cystectomy >12 weeks (p=0.044), pelvic lymphadenectomy status (p=0.014), and TNM stage >T3 (p<0.001) were determined to be independent risk factors of overall survival. Increasing severity of comorbidity statistically correlated with decreased overall survival after radical cystectomy.