• Asian Pacific Journal of Cancer Prevention
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• v.16 no.16
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• pp.7271-7275
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• 2015

The objective of this study was to determine the prevalence of significant lesions defined as high grade squamous intraepithelial lesions (HSIL), adenocarcinoma in situ (AIS) and invasive carcinoma in women who had HPV-positive and cytology negative co-testing screening results. This retrospective study was conducted in Chiang Mai University Hospital between May, 2013 and August, 2014. Hybrid capture 2 (HC2) was used for HPV testing and conventional Pap smears for cytologic screening. A repeat liquid-based cytology (LBC) was performed in women with such co-testing results followed by colposcopy. Random biopsy was performed in cases of normal colposcopic findings. Further investigations were carried out according to the biopsy or the repeat LBC results. During the study period, 273 women met the criteria and participated in the study. The mean age of these women was 46.4 years with 30% of them reporting more than one partner. The median interval time to colposcopy was 165 days. About 40% showed an abnormality in the repeat cytology. Significant cervical lesions were found in 20 (7.3%) women, including 2 invasive cancers. Of interest was that only 2 of 20 significant lesions were diagnosed by colposcopic examination while the remainder were initially detected by cervical biopsy and abnormal repeat cytology. In conclusion, the prevalence of significant cervical lesions in HPV positive and cytology negative women in Northern Thailand was 7.3%. Further diagnostic work up with repeat cytology follow by colposcopy is recommended. Random biopsy should be performed even when the colposcopic findings are normal.

• Journal of Chest Surgery
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• v.50 no.5
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• pp.329-338
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• 2017

Background: The clinical value of 3-field lymph node dissection (3FLND) in esophageal squamous cell carcinoma (ESCC) remains controversial. This study aimed to identify the patterns and prognostic significance of cervical lymph node metastasis (CLNM) in ESCC. Methods: A retrospective review of 77 patients with E SCC who underwent esophagectomy and 3FLND between 2002 and 2016 was conducted. For each cervical node level, the efficacy index (EI), overall survival, recurrence rate, and complication rate were compared. Results: CLNM was identified in 34 patients (44.2%) who underwent 3FLND. Patients with CLNM had a significantly lower overall survival rate (22.7% vs. 58.2%) and a higher recurrence rate (45.9% vs. 16.3%) than patients without CLNM. CLNM was an independent predictor of recurrence in ESCC patients. Moreover, in patients with pathologic N3 tumors, the odds ratio of CLNM was 10.8 (95% confidence interval, 2.0 to 57.5; p=0.005). Level IV dissection had the highest EI, and level IV metastasis was significantly correlated with overall survival (p=0.012) and recurrence (p=0.001). Conclusion: CLNM was a significant prognostic factor for ESCC patients and was more common among patients with advanced nodal stages. Level IV exhibited the highest risk of metastasis, and dissection at level IV may be crucial when performing 3FLND, especially in advanced nodal stage disease.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2869-2873
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• 2014

Background: Human papillomavirus (HPV) integration within the E2 gene has been proposed as a critical event in cervical carcinogenesis. This study concerned whether HPV16 status and E2 gene intactness are predictive of radiation response in patients with cervical cancer. Materials and Methods: Biopsies of 44 patients with cervical cancer were collected before or after radiotherapy. The presence of HPV16 was assessed by polymerase chain reaction (PCR) using specific primers for the L1 region. E2 disruption was detected by amplifying the entire E2 gene. Results: HPV16 DNA was found in 54.5% of the clinical samples. Overall, 62.5% of the HPV16 positive tumors had integrated viral genome and 37.5% had episomal genome. There was a tendency of increase of HPV16 E2 negative tumors compared with HPV16 L1 ones in advanced stages (75% versus 20% in stage III respectively). Detection of E2 gene appeared influenced by the radiotherapy treatment, as the percentage of samples containing an intact HPV16 E2 was more frequent in pretreated patients compared to radiotherapy treated patients (66.6% versus 20%). The radiation therapy caused an eight-fold [OR= 8; CI=1.22-52.25; p=0.03] increase in the risk of HPV16 genome disruption. The integration status is influenced by the irradiation modalities, interestingly E2 disruption being found widely after radiotherapy treatment (75%) with a total fractioned dose of 50Gy. Conclusions: This study reveals that the status of the viral DNA may be used as a marker to optimize the radiation treatment.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.11
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• pp.4751-4758
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• 2015

Echinodermata use saponins in chemical defense against pathogens and predators. The molecular mechanisms of antimetastatic effects of brittle star saponins are still unknown. The present study examined antioxidant capacity and invasive ability in HeLa carcinoma cells exposed to brittle star crude saponins. Discolorating methods with DPPH and ABTS and expression of SOD-2 with RT-PCR were used to estimate the antioxidant activity. The anti-invasive activity of extracted saponins was examined through adhesion of HeLa cells to extracellular matrix, wound healing and evaluation of the mRNA levels of MMP-2 and MMP-9 by real time-PCR. The results showed that extracted saponins had cytotoxicity against cervical cancer cells and ABTS and DPPH scavenging properties with $IC_{50}$ values of 604.5, $1012{\mu}g/ml$, respectively. Further, we found that, in wound healing assay, brittle star saponins could prevent invasion of HeLa cells in a concentration dependent manner. Furthermore, cell adhesion assay demonstrated blockage of cell attachment to extracellular matrix with an $IC_{50}$ concentration of $16.1{\mu}g/ml$. The significant dose dependent down regulation of MMP-2 and MMP-9 in treated cells demonstrated that isolated saponins can decline tumor metastasis in vitro. The brittle star saponins remarkably prevented cervical cancer invasion and migration associated with down regulation of matrix metalloproteinase expression. Therefore, saponins could be suggested as an anti-invasive candidate against cervical cancer and an antioxidant as well.

• Biomedical Science Letters
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• v.2 no.2
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• pp.153-158
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• 1996

Verapamil, a potent calcium channel blocker, has been proved to be one of the modulators to overcome drug resistance in cancer chemotherapy. In the present experiment, the possibility of verapamil as a MDR modulator was investigated by using MTT assay. Sole treatment of verapamil on the HeLa and Caski cervical cancer cell line revealed dose dependent cytotoxicity within a range of tested dose. Combined treatment of verapamil with 5-FU, DDP on two human cervical cancer cell line led to a significant synergistic cytotoxicity. Therefore , these studies showed that verapamil had a possibility to be applicable to cancer chemotherapy in gynecological oncology.

• Asian Pacific Journal of Cancer Prevention
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• v.14 no.9
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• pp.5385-5389
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• 2013

Background: For more than 80 years, the standard treatment of locally advanced cervical cancer was radiotherapy. However, based on several phase III randomized clinical trials in the past decade, concurrent cisplatin-based chemoradiotherapy is the current standard for this disease. Gemcitabine has potent radiosensitizing properties in preclinical and clinical trials, so it can be utilized simultanously with radiation. Materials and Methods: Thirty women with untreated invasive squamous cell carcinoma of the cervix of stage IIB to stage IVA were enrolled in the study in the Radiation Oncology Department of Imam Khomeini Hospital in Tehran from September 2009 to September 2010. Sixty $mg/m^2$ gemcitabine followed by $35mg/m^2$ cisplatin were concurrently administered with radiotherapy to the whole pelvic region on day one of each treatment week for five weeks. One and three months after treatment, patients underwent a complete physical examination and MRI to determine the response to treatment. Results: The mean age of patients was $58.1{\pm}11.8$ (29-78) years. After 3 months of treatment, 73.3%had complete and 26.7% demonstrated partial response to treatment. Grade 3 anemia was seen in 10%, grade 3 thrombocytopenia in 3.3% and grade 3 leukopenia in 10% of the patients. Conclusions: According to the positive results of this study in stage IIB, further phase II and III clinical trials are suggested to evaluate the role of chemoradiation using Gemcitabine for advanced cervical cancers.

• Radiation Oncology Journal
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• v.11 no.2
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• pp.347-354
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• 1993

This is a retrospective analysis of 67 patients with histologically proven invasive carcinoma of uterine cervix treated with surgery followed by adjuvant radiotherapy at Inje University Seoul Paik Hospital between october 1983 and september 1991, Postoperative radiotherapy was carried out in patients with high risks of locoregional recurrence such as positive pelvic lymph node (38 pts), large tumor size more than 3 cm (22 pts), cervical stromal invasion more than 2/3 (46 pts), parametrial involvement (9 pts), positive resection margin (14 pts), endo/myometrial extension (10 pts), and angiolymphatic invasion (13 pts). Stage I A, I B, and IIA were 2 $(3\%),$ 39 $(58.2\%),\;and\;26\;(38.8\%),$ respectively. Median follow-up period was 48 months with ranges from 13 to 115 months. All 67 patients were treated externally with standard pelvic field with radiation dose ranging from 4080 to 6120 cGy in 4~6 weeks period of time. Of these, 45 patients received intracavitary radiotherapy. The overall survival rate and disease free survival rate at 5-year were $88.0\%\;and\;82.1\%,$ respectively. The survival rates by stage were $87.1\%$ in IB and $88.4\%$ in IIA. Local control rate was $80.6\%(58\;pts).$ The treatment failure was noted in 12 of 67 patients $(17.9\%):$ locoregional failure in $7(10.4\%),$ distant metastasis in 3 $(4.5\%),$ and locoregional and distant metastasis in $2(3\%),$ The univariate analysis of prognostic factors disclosed endo/myometrial extension as a significant factor of survival and recurrence $(70.0\%\;vs\;91.1\%\;P<0.05\;&\;30.0\%\;vs\;15.8\%,\;respectively).$ The complication of postoperative radiothrapy was not significant and all patient were well tolerated. In conclusion, postoperative radiotherapy in patients with high risks of locoreginal recurrence is relatively well tolerated and it gives significantly improved survival rate especially in patients with positive lymph nodes, bulky tumor size $(\geqq3\;cm),$ parametrial involvement, cervical stromal invasion more than 2/3, positive resection margin and angiolymphatic invasion.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.7
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• pp.2947-2951
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• 2015

Background: The phenomenon of occult carcinoma maybe observed in patients with clinically unilateral papillary thyroid microcarcinoma (PTMC). Although many studies have reported that the $BRAF^{T1799A}$ mutation is associated with aggressive PTMC, the relationship between $BRAF^{T1799A}$ mutation and occult carcinoma is unclear. The aim of this study was to investigate the risk factors, including $BRAF^{T1799A}$ mutation, for occult contralateral carcinoma in clinically unilateral PTMC accompanied by benign nodules in the contralateral lobe. Materials and Methods: From January 2011 to December 2013, we prospectively enrolled 89 consecutive PTMC patients with clinically unilateral carcinoma accompanied by benign nodules in the contralateral lobe who received a total thyroidectomy and cervical lymph node dissection. $BRAF^{T1799A}$ mutation was tested by pyrosequencing on postoperative paraffin specimens. The frequency and predictive factors for occult contralateral carcinoma were analyzed with respect to the following variables: age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or $BRAF^{T1799A}$ mutation. Results: A total of 36 patients (40.4%) had occult PTMC in the contralateral lobe. The median diameter of the occult tumors was $0.33{\pm}0.21cm$. The $BRAF^{T1799A}$ mutation was found in 38 cases (42.7%). According to the univariate analysis, there were no significant differences between the presence of occult contralateral carcinoma and age, gender, family history, tumor size, presence of Hashimoto thyroiditis, extrathyroidal extension, central lymph node metastasis, multifocality of primary tumor, or $BRAF^{T1799A}$ mutation. Conclusions: Using current methods, it is difficult to preoperatively identify patients with PTMC, and further research is needed to determine predictive factors for the presence of occult contralateral carcinoma in patients with unilateral PTMC.

• Korean Journal of Head & Neck Oncology
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• v.36 no.2
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• pp.73-77
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• 2020

Ovarian cancer is common malignant disease with high mortality in the female. However, lymph node metastasis in the head and neck of ovarian cancer is very rare than in para-aortic, pelvic lymph node. A 49-year-old female patient came to our clinic with a left neck mass. After total thyroidectomy and left selective neck dissection for the cervical neck level II, III, IV, V, VI for ovarian cancer and thyroid cancer, she had already undergone chemotherapy (Paclitaxel+Carboplatin) 18 month ago. CT scan showed only lymph node enlargement in left neck level II. Positron emission tomography-computed tomography (PET-CT) revealed a hypermetabolic lesion in same area but no other hypermetabolic lesion, especially in the pelvic and abdominal cavity. Fine needle aspiration cytology revealed metastatic carcinoma. The serum level of CA-125 was elevated to 43.8U/mL, whereas other tumor markers (CA 19-9, CEA) were in the normal range. She underwent a revision of selective neck lymph node dissection for the cervical neck levels I, II, and III, and on the review of surgical pathology, metastatic carcinoma was suspected. Thus, we performed immunohistochemical staining for the tissue; as a result, it was finally diagnosed as metastatic ovarian cancer (positive for CK7, ER and PR, and negative for CK20). Adjuvant chemotherapy (Paclitaxel+Carboplatin) was planned on the tumor board, and the patient successfully received chemotherapy.

• The Journal of Korean Obstetrics and Gynecology
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• v.19 no.4
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• pp.47-60
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• 2006

Purpose : This study was conducted to investigate the inhibitory effects of Scutellaria barbata D. D on on the cell proliferation of HeLa Cells. Methods : Human uterine cervical carcinoma HeLa cells were cultured in the 1%, 5% and 10% concentration of Scutellaria barbata D. D on solution for 24, 48 and 72 hours for the direct inhibitory effects of Scutellaria barbata D. D on. Then we examined the effect of Scutellaria barbata D. D on solution on the cell proliferation inhibition by XTT assay. DNA fragmentation, MAP kinase activity and caspase activity by FACS analysis in HeLa cells. Results : We found that the proliferation of HeLa cells was significantly decreased in Scutellaria barbata D. D on solution containing groups comparing with a control group in a concentration-dependant manner. When HeLa cells were cultivated for 24 hours with 5% Scutellaria barbata D. D on solution containing group, the percentage of HeLa cells with activated caspase was the highest. Scutellaria barbata D. D on solution reduced the MAP kinase activity of HeLa cells comparing with the control group. By the XTT assay, the cell's activity was decreased in 5% and 10% Scutellaria barbata D. D on solution containing groups in 24 and 72 hours cultivation and 10% group in 48 hours. DNA fragmentation and caspase-3 activity of HeLa cells, however, were changed insignificantly. Conclusion : From this study we could suggest that Scutellaria barbata D. D on is available to the inhibition and apoptosis of human cervical carcinoma cell line, HeLa cells in vitro.