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ABSTRACT: AIM: The goal of this study was to evaluate the long-term outcomes of laparoscopic colposuspension to the Cooper's ligament after hysterectomy for uterovaginal prolapse. MATERIAL AND METHODS: We performed chart reviews of 43 patients with uterovaginal prolapse who underwent laparoscopic colposuspension to the Cooper's ligament after hysterectomy at Daejeon St. Mary's Hospital, Catholic University of Korea from 2003 to 2009. These patients exhibited grade 3 (29 patients) or grade 4 (14 patients) uterovaginal prolapse. RESULTS: The mean age was 63.2 years (range, 39-76). The mean follow-up period was 44.2 months (95% CI, 36.8-51.5). Forty-three patients showed no sign or recurrence of prolapse. Postoperative complications were tolerable and curable. Urinary frequency (2 patients, 4.7%), voiding difficulty (2 patients, 4.7%), nocturia (1 patient, 2.3%) and vaginal spotting (1 patient, 2.3%) were reported. CONCLUSION: Laparoscopic colposuspension using Cooper's ligament after hysterectomy could be an effective surgical option for the treatment of uterovaginal prolapse.
Journal of Obstetrics and Gynaecology Research 11/2012; · 0.94 Impact Factor
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ABSTRACT: The aim of this study was to identify novel genes following genomic DNA copy number changes using a genome-wide array-based comparative genomic hybridization (array-CGH) analysis in uterine leiomyosarcoma (ULMS).
Genomic DNA copy number changes were analyzed in 15 cases of ULMS from St Mary's Hospital of the Catholic University of Korea. The paraffin-fixed tissue samples were micro-dissected under microscope, and DNA was extracted. Array-based CGH and genomic polymerase chain reaction were carried out with statistical analyses such as hierarchical clustering and Gene Ontology.
All of 15 cases of ULMS showed specific gains and losses. The percentage of average gains and losses were 8.4 and 16.6 %, respectively. The analysis limit of average gains and losses was 40 %. The regions of high level of gain were 1q23.3, 7p14.2, 7q34, 7q35, 7q36.3, 13q34, and 16p13.3. And the regions of homozygous loss were 2q21.1, 2q22.1, 2p23.2, 12q23.3, 4q21.22, 4q34.3, 11q24.2, 12q23.3, 13q13.1, 13q21.33, and 14q24.3. In ULMS samples, recurrent regions of gain were 1p36.33, 1p36.32, 5q35.3, 7q36.3, and 8q24.3 and recurrent regions of loss were 1p31.1-p31.3, 1p32.1-p32.3, 2p12, 2p13.3, 2p14, 2p16.2-p16.3, 2q12.1-q12.3, 2q21.1-q21.2, 2q22.2-q22.3, 2q34, 2q36.1-q36.3, 5q21.3, 5q23.3, 5q31.1, 6p11.2, 6p12.1, 10q11.23, 10q21.2-q21.3, 10q23.2, 10q23.31, 10q25.1-q25.2, 10q25.3, 10q26.13, 10q26.2-q26.3, 11p11.2, 11p11.12, 11p12, 11p13, 11p15.4, 11q23.1-q23.2, 11q23.3, 13q14.12, 13q14.13-13q14.2, 13q14.2, 13q14.2, 13q14.3, 13q21.33, 13q22.1-q22.3, 14q24.2, 14q24.3, 14q31.1, 14q32.33, 15q11.2-q13, 15q14, 16q22.3, 16q23.1, 16q23.2, 16q24.1, 20p12.1, and 21q22.3. Representative frequently gained BAC clones encoded genes were HDAC9, CRR9, SOX18, PTPRN2, SKI, SOLH, and KIAA1199. The genes encoded by frequently lost BAC clones were LOC150516 and AMY2A. A subset of cellular processes from each gene were clustered by Gene Ontology database.
The present study using array-CGH analyses sought a deeper elucidation of the specific genomic alterations related to ULMS. The high resolution of array-CGH combined with human genome database would give a chance at identifying relevant target genes.
Journal of Cancer Research and Clinical Oncology 03/2012; 138(7):1173-86. · 2.56 Impact Factor
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Journal of Cancer Research and Clinical Oncology 01/2012; · 2.56 Impact Factor
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ABSTRACT: To evaluate the correlation tendency between abnormal findings of digital cervicography and cervical pathology at private clinics in Korea.
Abnormal finding of digital cervicography performed at private clinics in Korea between January 1, 2010 and May 31, 2012 were analysed retrospectively. The patient's age, abnormal findings of digital cervicography, cervical cytology, human papillomaviru (HPV) test and cervical pathology were investigated and the rate of agreement between abnormal finding of digital cervicography and cervical pathology results was calculated. Abnormal findings of digital cervicography were divided into 4 categories: atypical, compatible with CIN1, compatible with CIN2/3 and compatible with cancer.
The study group was composed of 1547 women with a mean (range) age of 37.4 (14-91 years). The agreement rate between abnormal findings of digital cervicography and cervical pathology was 52.0% in "compatible with CIN1", 78.9% in "compatible with CIN2/3", and 90.2% in "compatible with cancer".
Abnormal findings of digital cervicography were highly concordant with cervical intraepithelial neoplasia (CIN) and cancer examined at outpatient clinics in Korea. Therefore, abnormal interpretations of digital cervicography can be used as an excellent auxiliary technique with cervical cytology for CIN and cancer.
International journal of medical sciences 01/2012; 9(8):698-703. · 2.24 Impact Factor
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ABSTRACT: To evaluate whether the use of triweekly combination chemotherapy together with radiation exerts a more beneficial systemic effect than weekly cisplatin chemoradiation in patients with cervical cancer after radical surgery.
We retrospectively analyzed patients with stage IB1 to stage IIB cervical cancer who had undergone radical hysterectomy with pelvic lymph node dissection, followed by concurrent adjuvant chemoradiation therapy. The patients were divided into 2 groups: the triweekly combination chemotherapy group and the weekly cisplatin chemotherapy group. We evaluated the survival and adverse effects of the 2 groups.
In total, 201 patients were included. The mean duration of follow-up was 52.2 months. Of the 201 patients, 130 received triweekly combination chemotherapy, and 71 patients received weekly cisplatin chemotherapy as an adjuvant treatment. The 5-year disease-free survival was 82.2% for patients treated with weekly cisplatin chemotherapy and 74.3% for those treated with triweekly combination chemotherapy (P = 0.3929). The 5-year overall survival was 81.4% and 79.3% for the same treatment groups, respectively (P = 0.9833). The overall survival of the patients with stage IIB cervical cancer was marginally higher in the triweekly combination chemotherapy group than in the weekly cisplatin group (P = 0.0582). Leukopenia, neutropenia, thrombocytopenia, anemia, and hepatopathy were significantly more common in the triweekly combination chemotherapy group.
The weekly cisplatin chemotherapy group experienced the same therapeutic effect as the triweekly combination chemotherapy group but with less toxicity. Therefore, weekly cisplatin chemotherapy is considered the more useful concurrent adjuvant chemoradiation regimen after radical surgery.
International Journal of Gynecological Cancer 01/2011; 21(1):128-36. · 1.65 Impact Factor
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ABSTRACT: This study aims to evaluate the diagnostic value of stress perfusion MRI and SPECT for the detection of myocardial ischemia in patients with angiographically proven three-vessel coronary artery disease.
We retrospectively enrolled 78 patients with angiographically proven three-vessel coronary artery disease who underwent both stress perfusion MRI and SPECT within 4 weeks of each other. Image analysis was performed to compare the diagnostic value of stress perfusion MRI with that of SPECT; coronary angiography was used as the reference standard. The statistical significance of the difference between stress perfusion MRI and SPECT was evaluated by use of the paired McNemar test.
Myocardial ischemia was detected significantly more often by stress perfusion MRI than by SPECT, with more abnormal segments (mean +/- SD, 10.1 +/- 3.6 vs 4.9 +/- 2.6; p < 0.001) and abnormal vascular territories (2.55 +/- 0.5 vs 1.64 +/- 0.7; p < 0.001) identified per patient. The overall sensitivity for identifying perfusion defects in three vascular territories was higher for stress perfusion MRI than for SPECT (84.6% vs 55.1%; p < 0.001). The sensitivity of stress perfusion MRI and SPECT for detecting any perfusion defect per patient was 100% and 96.2%, respectively. However, perfusion defects in all three vascular territories were detected in 57.7% of patients by stress perfusion MRI but in only 11.5% of patients by SPECT.
Stress perfusion MRI is superior to SPECT for detecting myocardial ischemia in patients with angiographically proven three-vessel coronary artery disease.
American Journal of Roentgenology 08/2010; 195(2):356-62. · 2.78 Impact Factor
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ABSTRACT: Venous thromboembolism (VTE) is a common complication in patients with malignant disease. Epidemiological studies have demonstrated an increased risk of subsequent cancer in the patients who are diagnosed with idiopathic venous thrombosis. Cancers of the breast, lung and ovary in women and adenocarcinomas of an unknown primary cancer are most strongly associated with thrombosis. Mucin-producing cancers are most often associated with VTE and the highest rates of VTE were found for cases of ovarian cancer, but the absolute risk of cancer after thrombosis is relatively low (about 2% over the first year) and so the benefit of screening for cancer in thrombosis patients seems limited. But as this case, the association between thrombosis and occult cancer shows the importance of this association for patients who have thrombosis that is unresponsive to anticoagulant therapy. Especially, we should recognize that such patients can undergo investigation for an underlying malignancy. Diagnostic laparoscopy of an adnexal mass for confirming cancer in the acute setting of deep vein thrombosis (DVT) was performed for our patient. We report here on a case of a patient with DVT in the upper and lower extremities before the diagnosis of ovarian cancer, and we briefly review of the relevant literature.
Cancer Research and Treatment 03/2010; 42(1):48-52.
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ABSTRACT: Primary fallopian tube carcinoma (PFTC) is a rare tumor that histologically and clinically resembles epithelial ovarian cancer. PFTC has a worse prognosis than ovarian cancer as it is not routinely suspected and so treatment may be delayed. The early clinical manifestations and a prompt investigation can often lead to a correct diagnosis at an early stage. The preoperative diagnosis is usually difficult, and most patients with PFTC undergo laparotomy with the presumed diagnosis of ovarian carcinoma according to the presence of an adnexal mass. PFTC can present preoperatively as a tubo-ovarian abscess and it should be considered in the differential diagnosis of acute pelvic peritonitis. PFTC should be suspected by clinicians even if the presenting symptoms are atypical. We report here on two cases of PFTC along with a brief review of the literature.
Cancer Research and Treatment 07/2009; 41(2):113-6.
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European journal of nuclear medicine and molecular imaging 01/2009; · 4.99 Impact Factor
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ABSTRACT: The standard treatment strategy of intracranial aneurysms includes either endovascular coiling or microsurgical clipping. In certain situations such as in giant or dissecting aneurysms, bypass surgery followed by proximal occlusion or trapping of parent artery is required.
The authors assessed the result of extracranial-intracranial (EC-IC) bypass surgery in the treatment of complex intracranial aneurysms in one institute between 2003 and 2007 retrospectively to propose its role as treatment modality. The outcomes of 15 patients with complex aneurysms treated during the last 5 years were reviewed. Six male and 9 female patients, aged 14 to 76 years, presented with symptoms related to hemorrhage in 6 cases, transient ischemic attack (TIA) in 2 unruptured cases, and permanent infarction in one, and compressive symptoms in 3 cases. Aneurysms were mainly in the internal carotid artery (ICA) in 11 cases, middle cerebral artery (MCA) in 2, posterior cerebral artery (PCA) in one and posterior inferior cerebellar artery (PICA) in one case.
The types of aneurysms were 8 cases of large to giant size aneurysms, 5 cases of ICA blood blister-like aneurysms, one dissecting aneurysm, and one pseudoaneurysm related to trauma. High-flow bypass surgery was done in 6 cases with radial artery graft (RAG) in five and saphenous vein graft (SVG) in one. Low-flow bypass was done in nine cases using superficial temporal artery (STA) in eight and occipital artery (OA) in one case. Parent artery occlusion was performed with clipping in 9 patients, with coiling in 4, and with balloon plus coil in 1. Direct aneurysm clip was done in one case. The follow up period ranged from 2 to 48 months (mean 15.0 months). There was no mortality case. The long-term clinical outcome measured by Glasgow outcome scale (GOS) showed good or excellent outcome in 13/15. The overall surgery related morbidity was 20% (3/15) including 2 emergency bypass surgeries due to unexpected parent artery occlusion during direct clipping procedure. The short-term postoperative bypass graft patency rates were 100% but the long-term bypass patency rates were 86.7% (13/15). Nonetheless, there was no bypass surgery related morbidity due to occlusion of the graft.
Revascularization technique is a pivotal armament in managing complex aneurysms and scrupulous prior planning is essential to successful outcomes.
Journal of Korean Neurosurgical Society 11/2008; 44(4):228-33. · 0.60 Impact Factor
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ABSTRACT: Serum Tg and I-131 WBS have been used to detect recurrent and metastatic thyroid cancers postoperatively. Tg is known to be more sensitive than I-131 WBS, and therefore, false-negative WBS cases with elevated Tg levels are frequently found. However, the clinical characteristics of false-negative Tg cases with positive WBS have not been clarified.
The authors evaluated 824 postoperative patients with differentiated thyroid carcinoma who underwent post-ablation/therapy I-131 WBS. Tg negativity was defined as a Tg level of < or = 2 ng/mL without TgAb under thyroid-stimulating hormone stimulation. Remission, recurrence, and metastasis were confirmed using pathologic or clinically findings.
Fifty-two patients (6.3%) with functioning metastasis and negativity for TgAb were Tg-negative and posttherapy I-131 WBS-positive (TgN group), and 128 patients with functioning metastases were Tg positive and WBS positive (TgP group). The TgN group consisted of 45 cases of cervical/mediastinal lymph node metastases (86.5%) and seven cases of distant metastasis to lung or bone by follow-up WBS. The TgN group demonstrated significantly higher profiles of regional involvement than the TgP group (P < 0.029). In 47 patients in the TgN group, metastatic uptake disappeared in 33, ameliorated in four, and persisted in ten during follow-up.
A significant number of differentiated thyroid cancer patients were Tg-/TgAb-negative despite a positive WBS finding. Cervical and mediastinal lymph nodes were predominant sites of metastasis in the TgN group. WBS should be undertaken routinely as a complementary modality to detect functioning recurrence and metastasis regardless of serum Tg results.
European Journal of Nuclear Medicine 09/2008; 36(2):172-9. · 4.53 Impact Factor
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Eun Kyung Park,
Su-Mi Bae,
Sun-Young Kwak,
Sung Jong Lee,
Yong-Wook Kim,
Chan-Hee Han,
Hyun-Jung Cho,
Kyung Tae Kim,
Young-Jae Kim,
Hyun-Jung Kim,
Woong Shick Ahn
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ABSTRACT: Immunotherapy with photodynamic therapy (PDT) offers great promise as a new alternative for cancer treatment; however, its use remains experimental. Here we investigated the utility of adenoviral delivery of interleukin-12 (AdmIL-12) as an adjuvant for PDT in mouse tumour challenge model. PDT was performed by irradiating Radachlorin in C57BL/6 mice transplanted with TC-1 cells. PDT plus AdmIL-12 treatment for tumour suppression as well as specific immune responses were evaluated with the following tests: in vitro and in vivo tumour growth inhibition, interferon-gamma (IFN-gamma) and tumour necrosis factor-alpha (TNF-alpha) assay, and cytotoxic T lymphocyte (CTL) assay. Direct intratumoral injection of AdmIL-12 resulted in a significant suppression of tumour growth compared to the control group. Treatment of PDT along with AdmIL-12 further enhanced antitumour effects significantly higher than either AdmIL-12 or PDT alone. This combined treatment resulted in complete regression of 9-mm sized tumour in every animal. We also evaluated immune responses induced by these treatments. Combined treatment significantly increased the production level of IFN-gamma and TNF-alpha compared with that by AdmIL-12 or PDT alone. PDT plus AdmIL-12 enhanced antitumour immunity through increased expansion of the CTL subset mediated by CD8+ T cells. Taken together, these results indicate that the high anti-cancer activity of PDT with AdmIL-12 is a powerful tool against cancer therapy and is a promising subject for further investigation.
Immunology 05/2008; 124(4):461-8. · 3.32 Impact Factor
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ABSTRACT: To estimate the effect and toxicity of bimonthly low-dose leucovorin (LV) and fluorouracil (5-FU) bolus plus continuous infusion(LV5FU2) with docetaxel combination chemotherapy in patients with inoperable or postoperative relapsed gastric cancer.
Total 27 patients are enrolled in this study. LV 20 mg/m(2) (bolus), 5FU 400 mg/m(2) (bolus), 5-FU 600 mg/m(2) (24-hour continuous infusion) on day 1, 2, 15, and 16, docetaxel 60 mg/m(2) (1-hour infusion) on day 15 every 4 weeks.
Total of 141 cycles were administered and response rate were 36.8% with 2 complete response (10.5%) and 5 partial response (26.3%) in 19 evaluable patients. The median response duration is 8.1 months (95% CI, 4.0 approximately 12.1). The median progression-free survival time is 6.7 months (95% CI, 5.0 approximately 8.5) and the median overall survival time is 11.9 months (95% CI, 4.8 approximately 19.1). The grade 3-4 toxicity of neutropenia (24.8%) and anemia (11.3%), neutropenic fever (2.8%) is observed. The grade 1 toxicity of injection site reaction is observed all patients and the grade 1-2 toxicity of alopecia is observed 60%.
LV5FU2 with docetaxel combination chemotherapy is effective and tolerable in patients with inoperable or postoperative relapsed gastric cancer.
Cancer Research and Treatment 04/2008; 40(1):11-5.
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Yong-Seok Lee,
Su-Mi Bae,
Sun-Young Kwak,
Dong-Chun Park,
Yong-Wook Kim,
Soo-Young Hur, Eun-Kyung Park,
Byoung-Don Han,
Young-Joo Lee,
Chong-Kook Kim,
Do Kang Kim,
Woong-Shick Ahn
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ABSTRACT: The tumor suppressor gene, p53, has been established as an essential component for the suppression of tumor cell growth. In this study, we investigated the time-course anticancer effects of adenoviral p53 (Adp53) infection on human ovarian cancer cells to provide insight into the molecular-level understanding of the growth suppression mechanisms involved in Adp53-mediated apoptosis and cell cycle arrest.
Three human cervical cancer cell lines (SiHa, CaSki, HeLa and HT3) were used. The effect of Adp53 infection was studied via cell count assay, cell cycle analysis, FACS, Western blot and macroarray assay.
Adp53 exerts a significant role in suppressing cervical cancer cell growth. Adp53 also showed growth inhibitory effects in each cell line, and it induced apoptosis and cell cycle arrest. Adp53 differentially regulated the expression of genes and proteins, and the gene expression profiles in the SiHa cells revealed that the p21, p53 and mdm2 expressions were significantly up-regulated at 24 and 48 hr. Western blot shows that the p21 and p53 expression-levels were significantly increased after Adp53 infection. In addition, in all cell lines, both the CDK4 and PCNA protein expression levels were decreased 48 h after Adp53 infection. Cell cycle arrest at the G1 phase was induced only in the SiHa and HeLa cells, suggesting that exogenous infection of Adp53 in cancer cells was significantly different from the other HPV-associated cervical cancer cells.
Adp53 can inhibit cervical cancer cell growth through induction of apoptosis and cell cycle arrest, as well as through the regulation of the cell cycle-related proteins. The Adp53-mediated apoptosis can be employed as an advanced strategy for developing preferential tumor cell-specific delivery.
Cancer Research and Treatment 06/2006; 38(3):168-77.
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ABSTRACT: As early as 10 min after adenosine stress, immediate post-stress wall motion can be evaluated on adenosine stress/rest Tl-201 gated myocardial SPECT. To widen the applications of Tl-201 in gated SPECT, we investigated the reproducibility of LV parameters (EF, EDV, and ESV), and the diagnostic competency of immediate post-stress wall motion evaluations obtained by adenosine stress/rest Tl-201 gated myocardial SPECT. Myocardial perfusion and wall motion were evaluated using a 5-point scoring system in 20-segment model using Cedas automatic gated software (AutoQUANT 4.3.1). The reproducibilities of LV parameters were examined through repeated acquisition (n=31). Diagnostic competency was evaluated vs. coronary angiography, and multivariate logistic regression analysis was used to determine whether stress abnormal perfusion (SSSp), stress abnormal wall motion (SSSwm), or reversible abnormal wall motion (SDSwm) predict coronary stenosis (>70%) (n=60). Two standard deviations for immediate post-stress wall motion were smaller than those for rest at EF (8.6 vs. 10.7%) and ESV (6.0 ml vs 8.4 ml). Univariate logistic regression analysis identified SSSp (p=0.006), SSSwm (p=0.016), and SDSwm (p=0.020) are significant predictors, but only SSSp (p=0.013) and SDSwm (p=0.039) were found to be significant by multivariate analysis. In addition, SSSwm or SDSwm were able to find undetected coronary artery disease in 54.5% (6/11) of patients with normal perfusion. We conclude that Tl-201 can be successfully applied to gated SPECT for immediate post-stress wall motion evaluation, and that reversible wall motion abnormality on adenosine stress/rest Tl-201 gated myocardial SPECT is an independent predictor of significant coronary artery disease.
The International Journal of Cardiovascular Imaging 05/2006; 22(2):213-22. · 2.29 Impact Factor
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ABSTRACT: Photodynamic therapy (PDT) has been reported to be effective for treating various tumors and to induce apoptosis in many tumor cells. In this study, we evaluated the ability of PDT combined with a tumor suppressor factor, recombinant adenovirus p53 (AdCMVp53), to induce apoptosis as well as cell growth inhibition in CaSki human cervical cancer cells and in nude mice with implanted CaSki cells. To examine levels of apoptosis, CaSki cells were treated with PDT and/or AdCMVp53, and an annexin V-staining assay was then conducted. In addition, Western blot analysis was done to identify p53 induction at the cellular and tumor tissue levels. PDT+AdCMVp53 cotreatment caused remarkable inhibition of CaSki cell proliferation, as compared with the individual treatments. In parallel with the inhibition of cell proliferation, the cotreatment caused a significantly greater increase in the annexin V-stained cell population compared with the individual treatments, as determined by fluorescence-activated cell-sorting analysis. The Western blotting assay also showed significantly more cellular p53 expressed after PDT+AdCMVp53 cotreatment than after each separate treatment. This was consistent with observations of tumor tissue in the mouse system. However, apoptosis- related protein, p21, was significantly suppressed by PDT+AdCMVp53 cotreatment, contrary to treatment with AdCMVp53 alone. Taken together, these findings suggest that PDT plus AdCMVp53 gene therapy exerts more potent antitumor effects on human cervical cancer cells, with induction of apoptosis at least through activation in p53 protein at the cellular and tumor tissue levels.
Human Gene Therapy 04/2006; 17(3):347-52. · 4.22 Impact Factor
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ABSTRACT: Human papillomavirus (HPV) infection play a significant role in cervical carcinogenesis, and HPV oncoprotein E7 has important functions in the formation and maintenance of cervical cancers. Interleukin-12 (IL-12) has been reported to induce cellular immune responses, and has also been demonstrated to suppress the growth of tumors and the expression of E7. Here, we investigate the utility of adenovirus E7 (AdE7) and adenovirus IL-12 (AdIL-12) for protection against TC-1 tumor using an animal model.
The antitumor effects induced by AdIL-12 and/or E7 were assessed by measurements of tumor size. E7-specific antibody and INF-gamma production in sera were measured, as were T-helper cell proliferative responses. Cytotoxic T-lymphocytes (CTL) and T cell subset depletion studies were also performed.
Infection of tumor sites with a combination of AdIL-12 and AdE7 resulted in an antitumor effect which was significantly more profound than that which resulted from singular infections with either AdIL-12 or AdE7. Combined infection resulted in regression of 9-mm-sized tumors in approximately 80% of our experimental animals as compared to the PBS group. Serum levels of E7-specific antibody and INF-gamma production, as well as T-helper cell proliferative responses, were found to be significantly higher in coinfected with AdIL-12 and AdE7 group than in single infection with either AdIL-12 or AdE7 group. CTL responses only exhibited by the AdIL-12 and AdE7 coinjected group suggested that these tumor suppression effects were mediated primarily by CD8+ and, to a lesser degree, by CD4+ T cells.
Combined injection with adenovirus carrying IL-12 and E7 induced significant antitumor immunity against TC-1 tumors. They may prove useful in clinical applications for the treatment of HPV-associated tumors.
Gynecologic Oncology 06/2005; 97(2):559-67. · 3.89 Impact Factor
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Eun-Kyung Park,
Young-Wook Kim,
Joon-Mo Lee,
Sung-Eun NamKoong,
Do-Gang Kim,
Heung-Jae Chun,
Byoung-Don Han,
Su-Mi Bae,
Hyun-Sun Jin,
Jeong-Im Sin,
Woong-Shick Ahn
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ABSTRACT: Human papillomavirus (HPV) infection has a significant role in cervical carcinogenesis, and HPV oncoprotein E7 plays an important part in the formation and maintenance of cervical cancer. Interleukin-12 (IL-12) has been reported to induce a cellular immune response, and to suppress the tumor growth and the E7 production. Here we describe the use of adenoviral delivery of the HPV 16 E7 subunit (AdE7) along with adenoviral delivery of IL-12 (AdIL-12) in mice with HPV-associated tumors.
Mice were injected with TC-1 cells to establish TC-1 tumor, and then they were immunized with AdIL-12 and/or AdE7 intratumorally. The anti tumor effects induced by AdIL-12 and/or E7 were evaluated by measuring the size of the tumor. E7-specific antibody and INF-gamma production in sera, and the T-helper cell proliferative responses were then measured. Cytotoxic T-lymphocyte (CTL) and T cell subset depletion studies were also performed.
Combined AdIL-12 and AdE7 infection at the tumor sites significantly enhanced the antitumor effects more than that of AdIL-12 or AdE7 single infection. This combined infection resulted in regression of the 9 mm sized tumors in 80% of animals as compare to the PBS group. E7-specific antibody and INF-gamma production in the sera, and the T-helper cell proliferative responses were significantly higher with coinfection of AdIL-12 and AdE7 than with AdIL-12 or AdE7 alone. CTL response induced by AdIL-12 and AdE7 in the coinjected group suggested that tumor suppression was mediated by mostly CD8+ and only a little by the CD4+ T cells.
IL-12 and E7 application using adenovirus vector showed antitumor immunity effects against TC-1 tumor, and this system could be use in clinical applications for HPV-associated cancer.
Cancer Research and Treatment 02/2005; 37(1):63-70.
