• Asian Pacific Journal of Cancer Prevention
• /
• 제15권13호
• /
• pp.5181-5186
• /
• 2014

Tumors have evolved numerous mechanisms by which they can escape from immune surveillance. One of these is to produce immunosuppressive cytokines. Transforming growth factor-${\beta}$(TGF-${\beta}$) is a pleiotropic cytokine with a crucial function in mediating immune suppression, especially in the tumor microenvironment. TGF-${\beta}$ produced by T cells has been demonstrated as an important factor for suppressing antitumor immune responses, but the role of tumor-derived TGF-${\beta}$ in this process is poorly understood. In this study, we demonstrated that knockdown of tumor-derived TGF-${\beta}$ using shRNA resulted in dramatically reduced tumor size, slowing tumor formation, prolonging survival rate of tumor-bearing mice and inhibiting metastasis. We revealed possible underlying mechanisms as reducing the number of myeloid-derived suppressor cells (MDSC) and $CD4^+Foxp3^+$ Treg cells, and consequently enhanced IFN-${\gamma}$ production by CTLs. Knockdown of tumor-derived TGF-${\beta}$ also significantly reduced the conversion of na$\ddot{i}$ve $CD4^+$ T cells into Treg cells in vitro. Finally, we found that knockdown of TGF-${\beta}$ suppressed cell migration, but did not change the proliferation and apoptosis of tumor cells in vitro. In summary, our study provided evidence that tumor-derived TGF-${\beta}$ is a critical factor for tumor progression and evasion of immune surveillance, and blocking tumor-derived TGF-${\beta}$ may serve as a potential therapeutic approach for cancer.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권4호
• /
• pp.1759-1767
• /
• 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
• /
• 제15권14호
• /
• pp.5951-5957
• /
• 2014

Background: Traditional Chinese Medicine (TCM) possesses several advantages for treating patients with hepatocellular carcinoma (HCC). The theory of 'Jianpi Huayu Therapy' rooted from 'Jin Kui Yao Lue'is one of the most important therapies in this respect. This study was conducted to investigate the clinical effect and safety of hepatectomy combining with 'Jianpi Huayu Therapy' in the treatment of HCC. Materials and Methods: One hundred and twenty patients with HCC were randomized allocated into hepatectomy combined with 'Jianpi Huayu Therapy' group (treatment group, n=60) and hepatectomy alone group (control group, n=60). Disease- free survival (DFS) and overall survival (OS) were the primary end-points. Liver function at the end of one week after surgery, complications, average days of hospitalization as well as performance status (PS) at the end of one month post operation were also compared. Results: No significant differences existed between two groups on baseline analysis (p>0.05). No treatment related mortality occurred in either group. Post-operative complications were detected among 14 patients (23.3%) in the treatment group, and 12 (20.0%) in the control group (p=0.658). Alanine aminotransferase (ALT) at the end of one week after operation was lower in the treatment than control groups (p=0.042). No significant differences in other indexes of liver function were discovered between two groups. Average days of hospitalization reduced by 0.9 day in treatment group than in control (p=0.034). During follow-up, 104 patients (86.6%) developed recurrence. The rates of 1-, 3-, and 5-year DFS and median DFS for all patients were 77.4%, 26.3%, 9.0% and 25.6 months (range, 6.0~68.0), respectively (78.2%, 29.2%, 14.3% and 28.7 months for the 48 patients in the treatment group and 75.0%, 23.3%, 6.4%, and 22.6 months for the 56 patients in the control group (p=0.045)). 101 patients had died at the time of censor, with 1-, 3-, and 5-year overall survival rates and median survival for all patients of 97.5%, 76.4%, 40.5% and 51.2 months (range, 10.0~72.0), respectively (98.3%, 78.0%, 43.6% and 52.6 months, for treatment and 96.7%, 74.7%, 37.4%, and 49.8 months, for controls, respectively (p=0.048)). Conclusions: Hepatectomy combined with 'Jianpi Huayu therapy'was effective in the treatment of HCC, and reduced post-operative recurrence and metastasis and improved DFS and OS of HCC patients.

• Journal of Acupuncture Research
• /
• 제20권3호
• /
• pp.141-153
• /
• 2003

To study the effects of anti-cancer, anti-metastasis and immune response improvement of herbal-acupuncture with Eclipta prostrata diffuse herba infusion solution(ELP-HAS), we injected ELP-HAS into Chok-samni(St36) of C57BL/6 mice implanted intravenously with B16-F10 melanoma. We have reached the following conclusion through the effect on the number of $CD25^+/CD4^+$, $CD8^+/CD3e^+$, $CD69^+/B220^+$, $NK1.1+/CD3e^+$ cells in mouse PBMCs, the effect on the pulmonary colony number, and the effect on MST(Median Survival Time) and ILS(Increase of Life Span) of C57BL/6 mice implanted intravenously with B16-F10 melanoma The results were obtained as follows: 1. In the experiment groups treated with ELP(Eclipta prostrata) Herbal-Acupuncture, the spleen cell proliferation in Balb/c mouse was significantly increased compared with control group. 2. In the experiment groups treated with ELP(Eclipta prostrata) Herbal-Acupuncture, the percentage of $CD25^+/CD4^+$, $CD8^+/CD3e^+$, $CD69^+/B220^+$, $NK1.1^+/CD3e^+$ cells in C57Bl/6 mouse PBMCs was increased compared with control group. 3. In the experiment groups treated with ELP(Eclipta prostrata) Herbal-Acupuncture, the pulmonary colony number of C57BL/6 mice implanted intravenously with B16-F10 melanoma was decreased significantly compared with control group. 4. In the experiment groups treated with ELP(Eclipta prostrata)Herbal-Acupuncture, MST(Median Survival Time) and ILS(Increase of Life Span) of C57BL/6 mice implanted intravenously with B16-F10 melanoma were increased significantly compared with control group.

• Radiation Oncology Journal
• /
• 제8권1호
• /
• pp.65-71
• /
• 1990

Between January,1974 and December 1980, fifty eight patients with locoregional recurrent breast carcinoma who did not have evidence of distant metastasis after initial treatment of surgery with or without adjuvant chemotherapy were treated with radiation therapy. Among them, five patients were excluded from this study because of incomplete record or incomplete treatment. The 5-year overall survival and disease free survival from the time of locoregional recurrence was $27\%\;and\;15\%$ respectively. In univariate analysis of prognostic variables, the clinical stage at initial diagnosis, recur duration, number of recurrence sites, size of recurrences, response to the treatment, remission duration were all found to have no significant effect on survival or disease free survival. On the other hand, menopausal status at initial diagnosis, number of positive node at initial surgery, whether or not the use of adjuvant chemotherapy after initial mastectomy had definite prognositc significance. In multivariate analysis of prognostic variables, remission duration, menopausal status at diagnosis, number of axillary node at mastectomy had definite prognostic significance. On the other hand, remission duration more than 12 months, premenopaus at initial mastectomy, less than four positive axillary lymph nodes at mastectomy predicted a good prognosis.

• Radiation Oncology Journal
• /
• 제31권3호
• /
• pp.138-146
• /
• 2013

Purpose: To analyze the results of locoregional and systemic therapy in the breast cancer patients with locoregional recurrence (LRR) after mastectomy. Materials and Methods: Seventy-one patients who received radiotherapy for isolated LRR after mastectomy between January 1999 and December 2009 were retrospectively reviewed. Among the 71 patients, 59 (83.1%) underwent wide excision and radiotherapy and 12 (16.9%) received radiotherapy alone. Adjuvant hormonal therapy was given to 45 patients (63.4%). Oncologic outcomes including locoregional recurrence-free survival, disease-free survival (DFS), and overall survival (OS) and prognostic factors were analyzed. Results: Median follow-up time was 49.2 months. Of the 71 patients, 5 (7%) experienced second isolated LRR, and 40 (56%) underwent distant metastasis (DM). The median DFS was 35.6 months, and the 3- and 5-year DFS were 49.1% and 28.6%, respectively. The median OS was 86.7 months, and the 5-year OS was 62.3%. Patients who received hormone therapy together showed better 5-year DFS and OS than the patients treated with locoregional therapy only (31.6% vs. 22.1%, p = 0.036; 66.5% vs. 55.2%, p = 0.022). In multivariate analysis, higher N stage at recurrence was a significant prognostic factor for DFS and OS. Disease free interval (${\leq}30$ months vs. >30 months) from mastectomy to LRR was also significant for OS. The patients who received hormone therapy showed superior DFS and showed trend to better OS. Conclusion: DM was a major pattern of failure after the treatment of LRR after mastectomy. The role of systemic treatment for LRR after mastectomy should be investigated at prospective trials.

• Radiation Oncology Journal
• /
• 제37권3호
• /
• pp.166-175
• /
• 2019

Purpose: This study aimed to investigate neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as prognostic factors in patients with locally advanced non-small cell lung cancer (NSCLC) who received concurrent chemoradiotherapy (CCRT). Materials and Methods: We retrospectively analyzed 66 patients with locally advanced NSCLC treated with definitive CCRT. Among these patients, 95% received paclitaxel/carboplatin or docetaxel/cisplatin. The median radiation dose was 66 Gy in 33 fractions. The NLR and PLR before/after CCRT were evaluated. The maximally selected log-rank test was used to obtain the cutoff values related to the overall survival (OS). Results: Patients with high post-CCRT NLR (>3.12) showed worse OS, locoregional progression-free survival (LRPFS), and distant metastasis-free survival (DMFS) than those with low NLR (2-year OS: 25.8% vs. 68.2%, p < 0.001; 2-year LRPFS: 12.9% vs. 33.8%, p = 0.010; 2-year DMFS: 22.6% vs. 38.2%, p = 0.030). Patients with high post-CCRT PLR (>141) showed worse OS and LRPFS than those with low PLR (2-year OS: 37.5% vs. 71.1%, p = 0.004; 2-year LRPFS: 16.5% vs. 40.3%, p = 0.040). Patients with high NLR change (>1.61) showed worse OS and LRPFS than those with low NLR change (2-year OS: 26.0% vs. 59.0%, p < 0.001; 2-year LRPFS: 6.8% vs. 31.8%, p = 0.004). The planning target volume (hazard ration [HR] = 2.05, p = 0.028) and NLR change (HR = 3.17, p = 0.025) were the significant factors for OS in the multivariate analysis. Conclusion: NLR change after CCRT was associated with poor prognosis of survival in patients with locally advanced NSCLC. An elevated NLR after CCRT might be an indicator of an increased treatment failure risk.

• Radiation Oncology Journal
• /
• 제37권3호
• /
• pp.215-223
• /
• 2019

Purpose: To determine prognostic significance of lymphovascular invasion (LVI) in prostate cancer patients who underwent adjuvant or salvage postoperative radiotherapy (PORT) after radical prostatectomy (RP) Materials and Methods: A total of 168 patients with prostate cancer received PORT after RP, with a follow-up of ≥12 months. Biochemical failure after PORT was defined as prostate-specific antigen (PSA) ≥0.2 ng/mL after PORT or initiation of androgen deprivation therapy (ADT) for increasing PSA levels regardless of the value. We analyzed the clinical outcomes including survivals, failure patterns, and prognostic factors affecting the outcomes. Results: In total, 120 patients (71.4%) received salvage PORT after PSA levels were >0.2 ng/mL or owing to clinical failure. The 5-year biochemical failure-free survival (BCFFS), clinical failure-free survival (CFFS), distant metastasis-free survival (DMFS), overall survival, and cause-specific survival rates were 78.3%, 94.3%, 95.0%, 95.8%, and 97.3%, respectively, during a follow-up range of 12-157 months (median: 64 months) after PORT. On multivariate analysis, PSA level of ≤1.0 ng/mL at the time of receiving PORT predicted favorable BCFFS, CFFS, and DMFS. LVI predicted worse CFFS (p = 0.004) and DMFS (p = 0.015). Concurrent and/or adjuvant ADT resulted in favorable prognosis for BCFFS (p < 0.001) and CFFS (p = 0.017). Conclusion: For patients with adverse pathologic findings, PORT should be initiated as early as possible after continence recovery after RP. Even after administering PORT, LVI was an unfavorable predictive factor, and further intensive adjuvant therapy should be considered for these patients.

• The Korean Journal of Nuclear Medicine
• /
• 제30권4호
• /
• pp.516-523
• /
• 1996

The purpose of this study was to evaluate the clinical usefulness of I-123 MIBG scintigraphy with early planar and SPECT image in the diagnosis of neuroendocrine tumors. We reviewed I-123 MIBG scintigraphies of 21 patients who had been suspected to have neuroendocrine tumors by CT or MRI findings. Early 4 hour planar and SPECT images were obtained in all patients and delayed (13-24 hour) planar images were performed in 17 patients. Final diagnoses were made by surgery, biopsy, or clinical follow up. Twelve patients were confirmed to have neuroendocrine tumors. With 4 hour planar and SPECT images, there were 9 true positives(6 pheochromocytomas, 1 paraganglioma, 1 neuroblastoma, and 1 medullary cancer of the thyroid), 8 true negatives(1 adrenal cortical adenoma, 1 malignant fibrous histiocytoma, 1 adenoma in colon and 5 benign nonfunctioning adrenal tumors), 1 false positive(hepatocellular carcinoma) and 3 false negatives(1 recurred medullary cancer of the thyroid, 1 liver metastasis of carcinoid tumor and 1 ganglioneuroma). The sensitivity and specificity of I-123 MIBG scintigraphy were 75% and 89%, respectively. SPECT images provided good anatomical correlation with CT or MRI. Delayed images showed increased tumor to background ratio in 5 out of 8 true positive patients, but did not change the diagnosis. In conclusion, early 4 hour images with I-123 MIBG is clinically convenient and useful method in the detection of neuroendocrine tumors, and SPECT images can provide good anatomical correlation with CT or MRI.

• Journal of Applied Biological Chemistry
• /
• 제58권3호
• /
• pp.219-226
• /
• 2015

The anticancer activity of a methanolic extract from lemon leaves (MLL) was assessed in MCF-7-SC human breast cancer stem cells. MLL induced apoptosis in MCF-7-SC, as evidenced by increased apoptotic body formation, sub-G1 cell population, annexin V-positive cells, Bax/Bcl-2 ratio, as well as proteolytic activation of caspase-9 and caspase-3, and degradation of poly (ADP-ribose) polymerase (PARP) protein. Concomitantly, MLL induced the formation of acidic vesicular organelles, increased LC3-II accumulation, and reduced the activation of Akt, mTOR, and p70S6K, suggesting that MLL initiates an autophagic progression in MCF-7-SC via the Akt/mTOR pathway. Epithelial-mesenchymal transition (EMT), a critical step in the acquisition of the metastatic state, is an attractive target for therapeutic interventions directed against tumor metastasis. At low concentrations, MLL induced anti-metastatic effects on MCF-7-SC by inhibiting the EMT process. Exposure to MLL also led to an increase in the epithelial marker E-cadherin, but decreased protein levels of the mesenchymal markers Snail and Slug. Collectively, this study provides evidence that lemon leaves possess cytotoxicity and anti-metastatic properties. Therefore, MLL may prove to be beneficial as a medicinal plant for alternative novel anticancer drugs and nutraceutical products.