• Asian Pacific Journal of Cancer Prevention
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• v.14 no.7
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• pp.4273-4278
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• 2013

Objective: We aimed to define clinicopathologic risk factors associated with regional recurrence (RR) and thus the effectiveness of postoperative radiotherapy (PORT) for neck control for head and neck squamous cell carcinomas (HNSCCs) with differing cervical lymph node status. Methods: A retrospective study was performed in 196 HNSCC patients with pathologically positive neck node (N+) to evaluate the high-risk factors for RR and to define the role of PORT in control after neck dissection and postoperative radiotherapy (PORT). Results: Overall, the RR rate after neck dissection and PORT was 29%. Extracapsular spread (ECS) was confirmed to be the only independent risk factor for RR. There were no significant risk factors associated with RR in the ECS- group. The 5-year disease-specific survival rate was 45%, which descended to 10% with the emergence of RR. Conclusions: ECS remains a determined risk factor for RR after neck dissection and PORT in patients with N+. PORT alone is not adequate for preventing RR in the neck with ECS after neck dissection. More intensive postoperative adjuvant therapies, especially combined chemotherapy and radiotherapy, are needed to prevent regional failure in HNSCC patients with ECS.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.9
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• pp.4205-4208
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• 2016

Background: The aim of this study was to analyse the expression of EGFR in newly diagnosed and recurrent glioblastoma multiforme (GBM). Materials and Methods: Our study included a total of 48 paired samples collected from 24 patients diagnosed with GBM. The intensity of EGFR cytoplasmatic staining was scored on a scale of 1-3+ (weak, intermediate or strong). Results: We found EGFR overexpression in 23 patients (96%) with newly diagnosed GBM, while all recurrent tumours overexpressed EGFR. Ten recurrent tumours (42%) had a lower expression than their new counterpart 13 tumours (54%) had a similar expression, and only one case (2%) had increased expression on recurrence. The expression of EGFR in newly diagnosed GBM was significantly correlated with EGFR expression in recurrent tumour (p = 0.036). In addition, new GBMs with strong EGFR expression had a mean relapse-free interval of 11.5 months (p=0.017). A benefit of combined therapy was observed in the radiotherapy-plus-chemotherapy group where the average time was 11 months (p=0.011), as compared with surgery/radiotherapy alone (average time 6.8 months). Conclusions: The present data show that EGFR is overexpressed in paired GBMs. The discrepancies of EGFR expression between the primary tumour and the recurrence suggest heterogeneity of GBMs but also unity at relapse.

• Radiation Oncology Journal
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• v.2 no.1
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• pp.11-20
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• 1984

The renewed interest in the use of hyperthermia in cancer therapy is bases on radiobiological and clinical evidence indicated that there may be a significant therapeutic advantage with the use of heat alone or combined with radiation or chemotherapy, There are many methods for generating heat for localized tumor as like radiofrequency, microwave, electromagnetic induction and ultrasound. But it is very difficult to be even thermal dose distribution and stable output of power and then the detection of temperature in tumor is difficult to be precise with thermocouples and semiconductor sensors. We designed the microwave heating generator, dipole antenna applicators and autometic temperature controlled thermocouples for localized hyperthermia on skin and in cavities. 1. The microwave generator with 120 W, 2,450MHz magnetron could be heating up to $40^{\circ}C\~50^{\circ}C\;for\;1\~2$ hours in living tissues. 2. The thermal dose distribution in tissue with microwave was described $42^{\circ}C\~44^{\circ}C$ with in 3 cm depth and $2\~6cm$ diameter area. 3. Skin surface heating applicator with spiral 3 times wave length antenna radiated high Power of microwave. 4, Intracavitary heating applicator with dipole antenna with autometic control temperature sensor kept up continuously constant temperature in tissue. 5. For constant thermal distribution, applied two steps power with 10W microwave after $17\~20W$ during first 10 minutes. 6. The cooling rate by blood flew in living tissue was rised as $10\%$ then meats.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3471-3476
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• 2012

Background and Objective: Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung cancer A549 cells. Methods: A549 cells were treated with TXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employed to examine alterations of ${\alpha}$-tubulin, heat shock protein 90 (hsp90), epidermal growth factor receptor (EGFR), and caspase-3 in response to the different exogenous stimuli. Results: Compared with single-agent treatment, co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, induced apoptosis, and caused cell cycle delay at the $G_2/M$ transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of ${\alpha}$-tubulin or hsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90. Conclusions: Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells. Such combinations may provide a more effective strategy for treating human lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5849-5854
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• 2013

Background: Apoptosis may be induced after Bcl-2 expression is inhibited in proliferative cancer cells. This study focused on the effect of autophagy activation by ABT737 on anti-tumor effects of epirubicin. Methods: Cytotoxic effects of ABT737 on the HepG2 liver cancer cell line were assessed by MTT assay and cell apoptosis through flow cytometry. Mitochondrial membrane potential was measured by fluorescence microscopy. Monodansylcadaverin (MDC) staining was used to detect activation of autophagy. Expression of p53, p62, LC3, and Beclin1, apoptotic or autophagy related proteins, was detected by Western blotting. Results: ABT737 and epirubicin induced growth inhibition in HepG2 cells in a dose- and time-dependent manner. Both ABT737 and epirubicin alone could induce cell apoptosis with a reduction in mitochondrial membrane potential as well as increased apoptotic protein expression. Further increase of apoptosis was detected when HepG2 cells were co-treated with ABT373 and epirubicin. Furthermore, our results demonstrated that ABT373 or epirubicin ccould activate cell autophagy with elevated autophagosome formation, increased expression of autophagy related proteins and LC3 fluorescent puncta. Conclusions: ABT737 influences cancer cells through both apoptotic and autophagic mechanisms, and ABT737 may enhance the effects of epirubicin on HepG2 cells by activating autophagy and inducing apoptosis.

• Radiation Oncology Journal
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• v.12 no.1
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• pp.91-98
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• 1994

Purpose: Despite apparently complete resection of cancer of the rectum, local recurrence rate was high. Radiation therapy has been used either alone or in combination with chemotherapy as an adjunct to surgery to reduce the risk of recurrence. This study was designed to evaluate the prognostic factors, survival rate and local recurrence rate of the rectal cancer who had received postoperative radiation therapy by retrospective analysis. Method: From 1982 to 1990, 63 patients with cancer of the rectum surgically staged as B2 or C disease received postoperative adjuvant radiation therapy after curative resection of tumor for cure. Postoperative radiation therapy was given to the whole pelvis(mean dose: 5040 cGy in 5-6weets) and perineum was included in irradiated field in case of abdominoperineal resection. Results: Three-year actuarial survival rate was 73.2$ \% $ overall, 87.7$ \% $ in stage B2+3 and 62.9$ \% $ in stage C2+3. Three-year disease-free survival rate was 69.5$ \% $ overall, 87.7$ \% $ in stage B2+3 and 56.8$ \% $ in stage C2+3, Three-year disease-free survival rate in anterior resection was 77.8$ \% $ and 44.4$ \% $ in abdominoperineal resection. The local recurrence rate was 15.9$ \% $ and distant failure rate was 20.6$ \% $. Severe late complication was small bowel obstruction in 6 patients and surgery was required in 4 patients(6.3$ \% $). The prognostic factors were stage(p=0.0221) and method of surgery(p= 0.0414) (anterior resection vs abdominoperineal resection). Conclusion: This study provides evidence supporting the use of postoperative radiation therapy for reducing the local recurrence rate in patients who have had curative resection of rectal cancer with involvement of perirectal fat or regional nodes or both(stage B2 and C).

• Biomolecules & Therapeutics
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• v.20 no.5
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• pp.470-476
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• 2012

Resveratrol, a chemopreventive agent, is rapidly metabolized in the intestine and liver via glucuronidation. Thus, the pharmacokinetics of resveratrol limits its efficacy. To improve efficacy, the activity of resveratrol was investigated in the context of sphingolipid metabolism in human gastric cancer cells. Diverse sphingolipid metabolites, including dihydroceramides (DHCer), were tested for their ability to induce resveratrol cytotoxicity. Exposure to resveratrol ($100{\mu}M$) for 24 hr induced cell death and cell cycle arrest in gastric cancer cells. Exposure to the combination of resveratrol and dimethylsphingosine (DMS) increased cytotoxicity, demonstrating that sphingolipid metabolites intensify resveratrol activity. Specifically, DHCer accumulated in a resveratrol concentration-dependent manner in SNU-1 and HT-29 cells, but not in SNU-668 cells. LC-MS/MS analysis showed that specific DHCer species containing C24:0, C16:0, C24:1, and C22:0 fatty acids chain were increased by up to 30-fold by resveratrol, indicating that resveratrol may partially inhibit DHCer desaturase. Indeed, resveratrol mildly inhibited DHCer desaturase activity compared to the specific inhibitor GT-11 or to retinamide (4-HPR); however, in SNU-1 cells resveratrol alone exhibited a typical cell cycle arrest pattern, which GT-11 did not alter, indicating that inhibition of DHCer desaturase is not essential to the cytotoxicity induced by the combination of resveratrol and sphingolipid metabolites. Resveratrol-induced p53 expression strongly correlated with the enhancement of cytotoxicity observed upon combination of resveratrol with DMS or 4-HPR. Taken together, these results show that DHCer accumulation is a novel lipid biomarker of resveratrol-induced cytotoxicity in human gastric cancer cells.

• Korean Journal of Head & Neck Oncology
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• v.3 no.1
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• pp.15-24
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• 1987

This study is limited to epidermoid carcinoma arising in the larynx. The 623 patients in this series comprised 1.6% of all malignant neoplasms seen during the 20-year period .from 1965 to 1984 ; it comprised 13.2% of all cancers of the head and neck registered during this period. The male: female ratio was 11:1, and the highest incidence was in the fifth decade of life. Analysis by anatomical site revealed that 51.7% were supraglottic, 36.1% glottic, and 6.8% subglottic in oriain. One-hundred eighty-nine(79%) were clinically Stage III or Stage IV lesions at the time of the first visit. Of the total of 263 cases, 113 refused treatment, 4 definite radiation for $T_1$. lesion,21 underwent palliative therapy only, and 125 underwent surgical management with intent to cure. This surgical category included 53 patients who had surgical treatment only and 72 who underwent combined therapy(preoperative radiation, postoperative radiation, or inductive chemotherapy followed by surgery and postoperative radiation). The surgical management varied from partial laryngectomy to widefield laryngectomy and ipsilateral neck dissection. In 14.4% pathologically positive node or nodes were found in the clinically negative contralateral neck nedes. Such contralateral spread was most common in supraglottic site of origin(222%). Combined modality of management was compared to single therapy. Although results at three years showed no difference in determinate disease-free survival between patients treated by surgery only and those treated by surgery followed by postoperative radiation therapy at 5 years a statistically significant difference emerged, only 36% of those receiving surgery alone surviving as compared to 65.4% in the surgery with radiation group.

• Molecules and Cells
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• v.38 no.5
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• pp.396-401
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• 2015

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important redox-sensitive transcription factor that regulates the expression of several cytoprotective genes. More recently, genetic analyses of human tumors have indicated that Nrf2 may cause resistance to chemotherapy. In this study, we found that the expression levels of Nrf2 and its target genes GCLC, HO-1, NQO1 were significantly higher in cisplatin-resistant A549 (A549/CDDP) cells than those in A549 cells, and this resistance was partially reversed by Nrf2 siRNA. 3,4,5,5,7-Pentamethoxyflavone (PMF), a natural flavon extracted from Rutaceae plants, sensitized A549/CDDP to CDDP and substantially induced apoptosis compared with that of CDDP alone treated group, and this reversal effect decreased when Nrf2 was downregulated by siRNA. Mechanistically, PMF reduced Nrf2 expression leading to a reduction of Nrf2 downstream genes, and in contrast, this effect was decreased by blocking Nrf2 with siRNA. Taken together, these results demonstrated that PMF could be used as an effective adjuvant sensitizer to increase the efficacy of chemotherapeutic drugs by downregulating Nrf2 signaling pathway.

• Biomolecules & Therapeutics
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• v.15 no.3
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• pp.145-149
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• 2007

We have previously shown that 2,4,3',5'-tetramethoxystilbene (TMS), a synthetic trans-stilbene analogue acting as a potent inhibitor of human cytochrome P450 1B1, induces apoptotic cell death in human cancer cells. In the present studies, we report the mechanisms of apoptotic cell death by TMS in human promyelocytic leukemic HL-60 cells. We found that treatment of HL-60 cells with TMS suppressed the cell growth in a concentration-dependent manner with $IC_{50}$ value of about 0.8 ${\mu}M$. Immunoblot experiments revealed that DMHS-induced apoptosis was associated with cleavage of poly (ADP-ribose) polymerase. The release of cytochrome c from mitochondria into the cytosol was significantly increased in response to TMS. TMS caused activation of caspase-3 in a concentration-dependent manner and TMS-mediated caspase-3 activation was partially prevented by the caspase inhibitor, zVAD-fmk. Interestingly, we found that the cytotoxic effect of anticancer drugs such as paclitaxel, docetaxel, or etoposide was enhanced in the presence of TMS. Simultaneous treatment with TCDD also significantly increased cytotoxic effects of TMS alone or TMS and anti-cancer agents. Taken together, our present results indicated that TMS leads to apoptotic cell death in HL-60 cells through activation of caspase-3 activity and release of cytochrome c into cytosol. The ability of TMS to increase cytotoxic effect of anticancer drugs may contribute to its usefulness for cancer chemotherapy.