• Asian Pacific Journal of Cancer Prevention
• /
• 제16권10호
• /
• pp.4357-4361
• /
• 2015

Thunbergia Laurifolia Linn. (TL) is one of the most familiar plants in Thai traditional medicine that is used to treat various conditions, including cancer. However, the antitumor activity of TL or its constituents has never been reported at the molecular level to support the folklore claim. The present study was designed to investigate the antitumor effect of an aqueous extract of TL in human breast cancer cells and the possible mechanism(s) of action. An aqueous crude extract was prepared from dried leaves of TL. Folin-Ciocalteu colorimetric assays were used to determine the total phenolic content. Antiproliferative and cell cycle effects were evaluated in human breast adenocarcinoma MCF-7 cells by MTT reduction assay, cell growth inhibition, clonogenic cell survival, and flow cytometric analysis. Free radical generation by the extracts was detected using electron paramagnetic resonance spectroscopy. The exposure of human breast adenocarcinoma MCF-7 cells to a TL aqueous extract resulted in decreases in cell growth, clonogenic cell survival, and cell viability in a concentration-dependent manner with an $IC_{50}$ value of $843{\mu}g/ml$. Treatments with extract for 24h at $250{\mu}g/ml$ or higher induced cell cycle arrest as indicated by a significant increase of cell population in the G1 phase and a significant decrease in the S phase of the cell cycle. The capability of the aqueous extract to generate radical intermediates was observed at both high pH and near-neutral pH conditions. The findings suggest the antitumor bioactivities of TL against selected breast cancer cells may be due to induction of a G1 cell cycle arrest. Cytotoxicity and cell cycle perturbation that are associated with a high concentration of the extract could be in part explained by the total phenolic contents in the extract and the capacity to generate radical intermediates to modulate cellular proliferative signals.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제42권6호
• /
• pp.358-364
• /
• 2016

Objectives: To evaluate the results of elective neck dissection versus those of observation in the treatment of early stage oral squamous cell carcinoma and to identify factors related to recurrence and survival. Materials and Methods: This was a retrospective study of 52 patients who underwent elective neck dissection and 27 who did not receive neck dissection. Results: In survival analyses, elective neck dissection showed a benefit in overall recurrence (P=0.027), especially in stage I patients (P=0.024). With regard to survival, the benefit was statistically insignificant (P=0.990). In multivariable analysis, overall recurrence was independently related to poor histologic grade (odds ratio [OR]=9.65, P=0.006), and cancer-specific death was independently related to advanced age (OR=6.3, P=0.022), higher clinical T stage (OR=15.2, P=0.01), and poorly differentiated histologic grade (OR=6.6, P=0.025). Conclusion: Though there was lower recurrence in the elective neck dissection group, there were no statistically significant results on survival. The characteristics of the tumor itself, such as clinical T stage and poor histologic grade, may be more important in cancer-specific survival.

• BMB Reports
• /
• 제55권4호
• /
• pp.198-203
• /
• 2022

As negative regulators of cytokine signaling pathways, suppressors of cytokine signaling (SOCS) proteins have been reported to possess both pro-tumor and anti-tumor functions. Our recent studies have demonstrated suppressive effects of SOCS1 on epithelial to mesenchymal signaling in colorectal cancer cells in response to fractionated ionizing radiation or oxidative stress. The objective of the present study was to determine the radiosensitizing action of SOCS1 as an anti-tumor mechanism in colorectal cancer cell model. In HCT116 cells exposed to ionizing radiation, SOCS1 over-expression shifted cell cycle arrest from G2/M to G1 and promoted radiation-induced apoptosis in a p53-dependent manner with down-regulation of cyclin B and up-regulation of p21. On the other hand, SOCS1 knock-down resulted in a reduced apoptosis with a decrease in G1 arrest. The regulatory action of SOCS1 on the radiation response was mediated by inhibition of radiation-induced Jak3/STAT3 and Erk activities, thereby blocking G1 to S transition. Radiation-induced early ROS signal was responsible for the activation of Jak3/Erk/STAT3 that led to cell survival response. Our data collectively indicate that SOCS1 can promote radiosensitivity of colorectal cancer cells by counteracting ROS-mediated survival signal, thereby blocking cell cycle progression from G1 to S. The resulting increase in G1 arrest with p53 activation then contributes to the promotion of apoptotic response upon radiation. Thus, induction of SOCS1 expression may increase therapeutic efficacy of radiation in tumors with low SOCS1 levels.

• 대한약침학회지
• /
• 제7권3호
• /
• pp.77-88
• /
• 2004

Objectives ; This study was to investigate the anti-cancer effects of herbal acupuncture with distilled fresh ginseng. The herbal acupuncture was injected to Chung-wan($C.V_{12}$) and Wisu($BL_{21}$) of mice that were subjected to Sarcoma-180 adbominal cancer cell and A549 human epithelial lung cancer cells in vitro. Methods : Anti-cancer effects of distilled fresh ginseng herbal acupuncture were tested by measruing Cox, Bcl-2, and Bax by using RT-PCR in A549 human epithelial lung cancer cells in vitro. And four weeks old Balb/c line male mice weighing around $20\;{\pm}\;3g$ were used to measure survival rate and anti-cancer effect to outputs of interleukin-2 and interleukin-4 using flow cytometry, possibility of mRNA menifestation using RT-PCR, and Cox mRNA. The results are as follows. Results : 1. In measuring mRNA menifestation in Cox, Bcl-2, and Bax by using RT-PCR in A549 human epithelial lung cancer cells in vitro, the result showed that fresh ginseng decreased Cox-2 which is directly involved in Inflammation process. 2. Survival rate was measured in an anti-cancer effect experiment against Sarcoma-180 abdorminal cancer. Median survival time of controlled group was 27 days, of experiment group I was 21 days, and of experiment group II was 27 days. Therefore, experiment group I showed -22.2% increase in survival rate and experiment group II showed no difference compare to controlled group. 3. There was no difference between condition group and controlled and experiment group in measuring outputs of interleukin-2 and interleukin 4 by using flow cytometry 4. In measuring outputs of interleukin-2 by using ELISA, there was no significant difference between condition group and controlled group and there was decrease in experiment group II compared to conditioned and controlled group. 5. In measuring cytokine mRNA menifestation by using RT-PCR, experiment group I showed increase of mRNA menifestation in interleukin-2,4 and $interferon-{\gamma}$ and experiment group II showed no significant difference in $interferon-{\gamma}$. Conclusion : According to the results, fresh ginseng herbal-acupuncture took a little effects in cancer. In using distilled fresh ginseng herbal acupuncture has effect on Cox-2 decrease. However, the difference in concentration of fresh ginseng showed no effect on killing cancer cell. It is assumed that inaccurate concentration of herbal acupuncture and fresh ginseng component could be the reason for this result. Therefore, future consideration will be studies on herbal acupuncture concentration.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권10호
• /
• pp.6165-6171
• /
• 2013

This study aimed to analyze the expression and clinical significance of cyclin G2 (CCNG2) in thyroid carcinoma and the biological effects of CCNG2 overexpression in a cell line. Immunohistochemistry and Western blotting were used to analyze CCNG2 protein expression in 63 cases of thyroid cancer and normal tissues to allow the relationship with clinical factors to be assessed. CCNG2 lentiviral and empty vectors were transfected into the thyroid cancer K1 cell line. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting were applied to detect the mRNA and protein levels of CCNG2. MTT assay and cell cycle were also conducted to assess the influence of up-regulated expression of CCNG2 on K1 cell biology. The level of CCNG2 protein expression was found to be significantly lower in thyroid cancer tissue than normal tissues (P<0.05). Western blot: The relative amount of CCNG2 protein in thyroid cancer tissue was respectively found to be significantly lower than in normal tissues (P<0.05), correlating with lymph node metastasis, clinic stage and histological grade (P<0.05), but not gender, age or tumor size (P>0.05). Loss of CCNG2 expression correlated significantly with poor overall survival time on Kaplan-Meier analysis (P<0.05). The results for biological functions showed that K1 cell transfected CCNG2 had a lower survival fraction, a greater percentage in the G0/G1 phases, and lower cyclin-dependent kinase 2 (CDK2) protein expression compared with K1 cells non-transfected with CCNG2 (P<0.05). CCNG2 expression decreased in thyroid cancer and correlated significantly lymph node metastasis, clinic stage, histological grade and poor overall survival, suggesting that CCNG2 may play important roles as a negative regulator in thyroid cancer K1 cells by promoting degradation of CDK2.

• Preventive Nutrition and Food Science
• /
• 제12권4호
• /
• pp.197-201
• /
• 2007

Genistein is an active component of legumes and other related food shown to be associated with prevention of degenerative diseases such as cancer through inducing signaling pathways. Treatment of genistein resulted in the induction of apoptosis in the cultured cancer cells. This induction of apoptosis was demonstrated by the Tunel assay in these cells. Unveiling the potential of genistein in cytotoxicity via apoptosis when it is treated with estrogen can predict the therapeutic capability of genistein in breast cancers in the presence of endogenous estrogen. We have found that apoptosis induced by genistein treatment in the presence of estrogen is agonistic or antagonistic depending on the concentrations and treatment periods applied in MCF-7 breast cancer cells. For the suppression of cell survival, 24 hr of treatment was required to induce a synergistic agonistic response between estrogen and genistein at low concentrations of genistein. After this period, the agonistic pattern of genistein to estrogen disappeared. The decrement of COX-2 expression in MCF-7 cells treated with genistein was accompanied with the activation of AMPK only at a high concentration of genistein. This association between AMPK activation and down-regulation of COX-2 by genistein was dampened in the presence of estrogen. It was also demonstrated that genistein and estrogen regulate cell survival and apoptosis by modulating p53 and caspase-3 in the opposite direction. These results suggest that genistein has the potential to control breast cancer development, and co-treatment with estrogen can cause agonistic or antagonistic action on breast cancer cell control.

• Asian Pacific Journal of Cancer Prevention
• /
• 제15권2호
• /
• pp.731-736
• /
• 2014

Objective: To observe the short-term efficacy, long-term survival time and adverse responses with nedaplatin (NDP) or cisplatin (DDP) concomitant with other chemotherapy in treating non-small cell lung cancer. Materials and Methods: A retrospective, randomized, control study was conducted, in which 619 NSCLC patients in phases III and IV who were initially treated and re-treated were randomly divided into an NDP group (n=294) and a DDP group (n=325), the latter being regarded as controls. Chemotherapeutic protocols (CP/DP/GP/NP/TP) containing NDP or DDP were given to both groups. Patients in both groups were further divided to evaluate the clinical efficacies according to initial and re-treatment stage, pathological pattern, type of combined chemotherapeutic protocols, tumor stage and surgery. Results: The overall response rate (ORR) and disease control rate (DCR) in the NDP group were 48.6% and 95.2%, significantly higher than in the DDP group at 35.1% and 89.2%, respectively (P<0.01). In NSCLC patients with initial treatment, squamous carcinoma and phase III, there were significant differences in ORR and DCR between the groups (P<0.05), while ORR was significant in patients with adenocarcinoma, GP/TP and in phase IIIa (P<0.05). There was also a significant difference in DCR in patients in phase IIIb (P<0.05). According to the statistical analysis of survival time of all patients and of those in clinical phase III, the NDP group survived significantly longer than the DDP group (P<0.01). The rates of decreased hemoglobin and increased creatinine, nausea and vomiting in the NDP group were evidently lower than in DDP group (P<0.05). Conclusion: NDP concomitant with other chemotherapy is effective for treating NSCLC, with higher clinical efficacy than DDP concomitant with chemotherapy, with advantages in prolonging survival time and reducing toxic and adverse responses.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권3호
• /
• pp.1123-1127
• /
• 2016

Chemotherapy is the primary treatment for advanced and recurrent cervical cancer. To evaluate the survival outcomes of chemotherapy and the prognostic factors in this setting, we conducted a retrospective study by reviewing the medical records of advanced and recurrent cervical cancer patients treated with systemic chemotherapy at our institute between January, 2008 and December, 2014. One hundred and seventy-three patients met the criteria with a mean age of 50.9 years. 4.1% of them were HIV positive. The most common initial stage was stage IVB (30.1%) and the most common histology was squamous cell carcinoma (68.6%). Ninety-two (53.2%) patients were previously treated with concurrent chemoradiation with 53% developing combined sites of recurrence. The median recurrence free interval was 16.7 months. Cisplatin + 5 fluorouracil (5FU) (53.2%) was the most frequent first line chemotherapy followed by carboplatin + paclitaxel (20.2%) with an objective response of 39.3%. Seventy-two patients received subsequent chemotherapy. The median overall survival of all studied patients was 13.2 months. Only a recurrence free interval of less than 12 months was an independent prognostic factor for survival outcome. In conclusion, chemotherapy treatment for advanced and recurrent cervical cancer patients showed modest efficacy with a shorter recurrence free survival less than 12 months as a significant poor prognosis factor.

• Asian Pacific Journal of Cancer Prevention
• /
• 제17권4호
• /
• pp.2055-2060
• /
• 2016

Background: Colorectal cancer (CRC) is one of the most common causes of death worldwide and in Thailand. The X-ray repair cross-complementary protein 1 (XRCC1) is required for efficient DNA repair. The effects of this gene on survival in colorectal cancer remain controversial and have not been reported in Thailand. The aim of this study was to investigate the association of the XRCC1 gene with survival of colorectal cancer patients in a Thai population. Materials and Methods: Data and blood samples were collected from 255 newly diagnosed and pathologically confirmed CRC patients who were recruited during the period 2002 to 2006 and whose vital status was followed up until 31 October, 2014. Real-time PCR-HRM was used for genotype identification. The Kaplan-Meier method, the log-rank test, and Cox proportional hazard regression were used to estimate cumulative survival curves and compare various survival distributions and adjusted hazard ratios. Results: Most of the cases were males, and the median age was 55 years. The median survival time was 2.43 years. The cumulative 1-, 3-, 5-, 7-, and 10 year survival rates were 76.70%, 39.25%, 26.50%, 16.60% and 3.56%, respectively. After adjustment, female gender, ages 50-59 and ${\geq}60years$, tumour stage III+IV, a signet-ring cell carcinoma, and poor differentiation had significant associations with increased risk of CRC death. While the XRCC1 Arg/Arg homozygote appeared to be a risk factor for CRC death, the association was not significant. Conclusions: The genetic variant in the XRCC1 may not be associated with the survival of CRC patients in Thailand. Further studies are needed to verify our findings.

• Asian Pacific Journal of Cancer Prevention
• /
• 제14권5호
• /
• pp.2851-2857
• /
• 2013

Objective: REPS2 plays important roles in inhibiting cell proliferation, migration and in inducing apoptosis of cancer cells, now being identified as a useful biomarker for favorable prognosis in prostate and breast cancers. The purpose of this study was to assess REPS2 expression and to explore its role in esophageal squamous cell carcinoma (ESCC). Methods: Protein expression of REPS2 in ESCCs and adjacent non-cancerous tissues from 120 patients was analyzed by immunohistochemistry and correlated with clinicopathological parameters and patient outcome. Additionally, thirty paired ESCC tissues and four ESCC cell lines and one normal human esophageal epithelial cell line were evaluated for REPS2 mRNA and protein expression levels by quantitative RT-PCR and Western blotting. Results: REPS2 mRNA and protein expression levels were down-regulated in ESCC tissues and cell lines. Low protein levels were significantly associated with primary tumour, TNM stage, lymph node metastasis and recurrence (all, P < 0.05). Survival analysis demonstrated that decreased REPS2 expression was significantly associated with shorter overall survival and disease-free survival (both, P < 0.001), especially in early stage ESCC patients. When REPS2 expression and lymph node metastasis status were combined, patients with low REPS2 expression/lymph node (+) had both poorer overall and disease-free survival than others (both, P < 0.001). Cox multivariate regression analysis further revealed REPS2 to be an independent prognostic factor for ESCC patients. Conclusions: Our findings demonstrate that downregulation of REPS2 may contribute to malignant progression of ESCC and represent a novel prognostic marker and a potential therapeutic target for ESCC patients.