The AMPK-Parkin axis negatively regulates necroptosis and tumorigenesis by inhibiting the necrosome.

The receptor-interacting serine/threonine-protein kinases RIPK1 and RIPK3 play important roles in necroptosis that are closely linked to the inflammatory response. Although the activation of necroptosis is well characterized, the mechanism that tunes down necroptosis is largely unknown. Here we find that Parkin (also known as PARK2), an E3 ubiquitin ligase implicated in Parkinson's disease and as a tumour suppressor, regulates necroptosis and inflammation by regulating necrosome formation. Parkin prevents the formation of the RIPK1-RIPK3 complex by promoting polyubiquitination of RIPK3. Parkin is phosphorylated and activated by the cellular energy sensor AMP-activated protein kinase (AMPK). Parkin deficiency potentiates the RIPK1-RIPK3 interaction, RIPK3 phosphorylation and necroptosis. Parkin deficiency enhances inflammation and inflammation-associated tumorigenesis. These findings demonstrate that the AMPK-Parkin axis negatively regulates necroptosis by inhibiting RIPK1-RIPK3 complex formation; this regulation may serve as an important mechanism to fine-tune necroptosis and inflammation.

WSB1 overcomes oncogene-induced senescence by targeting ATM for degradation.

Oncogene-induced senescence (OIS) or apoptosis through the DNA-damage response is an important barrier of tumorigenesis. Overcoming this barrier leads to abnormal cell proliferation, genomic instability, and cellular transformation, and finally allows cancers to develop. However, it remains unclear how the OIS barrier is overcome. Here, we show that the E3 ubiquitin ligase WD repeat and SOCS box-containing protein 1 (WSB1) plays a role in overcoming OIS. WSB1 expression in primary cells helps the bypass of OIS, leading to abnormal proliferation and cellular transformation. Mechanistically, WSB1 promotes ATM ubiquitination, resulting in ATM degradation and the escape from OIS. Furthermore, we identify CDKs as the upstream kinase of WSB1. CDK-mediated phosphorylation activates WSB1 by promoting its monomerization. In human cancer tissue and in vitro models, WSB1-induced ATM degradation is an early event during tumorigenic progression. We suggest that WSB1 is one of the key players of early oncogenic events through ATM degradation and destruction of the tumorigenesis barrier. Our work establishes an important mechanism of cancer development and progression in premalignant lesions.

WSB1 promotes tumor metastasis by inducing pVHL degradation.

The von Hippel-Lindau tumor suppressor pVHL is an E3 ligase that targets hypoxia-inducible factors (HIFs). Mutation of VHL results in HIF up-regulation and contributes to processes related to tumor progression such as invasion, metastasis, and angiogenesis. However, very little is known with regard to post-transcriptional regulation of pVHL. Here we show that WD repeat and SOCS box-containing protein 1 (WSB1) is a negative regulator of pVHL through WSB1's E3 ligase activity. Mechanistically, WSB1 promotes pVHL ubiquitination and proteasomal degradation, thereby stabilizing HIF under both normoxic and hypoxic conditions. As a consequence, WSB1 up-regulates the expression of HIF-1α's target genes and promotes cancer invasion and metastasis through its effect on pVHL. Consistent with this, WSB1 protein level negatively correlates with pVHL level and metastasis-free survival in clinical samples. This work reveals a new mechanism of pVHL's regulation by which cancer acquires invasiveness and metastatic tendency.

Genetic polymorphism of PRKCDBP is associated with an increased risk of endometrial cancer.

PRKCDBP is a putative tumor suppressor located at 11p15.4, where frequent genomic loss has been observed in human cancers. We explored the possible association between an intra-exonic single nucleotide polymorphism (SNP), rs1051992, that results in a Leu to Pro substitution, and risk for endometrial carcinogenesis. We assessed the genotype of rs1051992 in endometrial cancer tissues from 147 patients and normal endometrial tissue from 191 healthy individuals by restriction endonuclease PvuII-based genotyping. Allele frequencies in the cancer specimens were compared with those in the healthy controls. We also evaluated the association between polymorphisms at this locus and histopathological features of endometrial cancer.

Efficacy of systematic pelvic lymphadenectomy in patients with non-endometrioid endometrial cancers: a retrospective, multicenter study in Korea.

AIM: Non-endometrioid endometrial cancer is a clinically and pathologically distinct subtype of endometrial cancer. The aim of this study was to determine whether systematic pelvic lymphadenectomy improves overall survival compared to no lymphadenectomy in non-endometrioid endometrial cancer. MATERIAL AND METHODS: The authors retrospectively reviewed the medical records and pathological findings of 112 patients who underwent surgical staging for non-endometrioid endometrial cancer from 2000 to 2006 in Korea. RESULTS: Systematic pelvic lymphadenectomy was performed in 71 patients. Pelvic lymph node metastases were identified in 31% and 14.6% patients who underwent systematic pelvic lymphadenectomy and no lymphadenectomy, respectively. After adjusting for risk factors, there was no significant difference in overall survival (odds ratio = 0.69; 95% confidence interval, 0.29-1.67) between patients who did or did not undergo systematic pelvic lymphadenectomy. On multivariate analysis, patients with lymph node metastasis had higher risk of death (odds ratio = 3.11; 95% confidence interval, 0.97-10.00) than the patients with no lymph node metastasis. CONCLUSION: Although systematic pelvic lymphadenectomy did not affect overall survival in patients with the non-endometrioid subtype, it has the potential benefit of providing prognostic information and acting as a guide for further adjuvant treatment.

Correlation between FDG uptake by PET/CT and the expressions of glucose transporter type 1 and hexokinase II in cervical cancer.

BACKGROUND: The aim of this study was to explore the association between 2-deoxy-2-F18-fluoro-D-glucose uptake and the expressions of glucose transporter type 1 (GLUT-1) and hexokinase II (HK-II) in the lymph nodes of patients with cervical cancer. METHODS: This prospective study included 20 women with International Federation of Gynecology and Obstetrics stage IB to stage IIA cervical cancer who underwent positron emission tomography (PET)-computed tomography (CT) (PET/CT) before surgical treatment. In 333 dissected lymph nodes (LNs) obtained, we examined the size, tumor involvement, and expressions of GLUT-1 and HK-II. These characteristics were compared with PET/CT and pathological findings. RESULTS: Pathological analysis found that 21% (70) of the 333 surgically dissected LNs were metastatic. Positron emission tomography/CT detected metastasis with 22.8% sensitivity and 98.5% specificity. The levels of GLUT-1 and HK-II expression in false-positive LNs were higher than those in pathologically confirmed negative nodes (P = 0.015 and P = 0.001, respectively). In metastatic LNs, PET/CT-positive nodes were significantly different from PET/CT-negative nodes in mean size (P = 0.043), tumor involvement (P = 0.008), and proportion of GLUT-1-positive tumor cells (P = 0.042). CONCLUSIONS: Our results indicate that overexpression of GLUT-1 and HK-II may be related to 2-deoxy-2-F18-fluoro-D-glucose uptake in false-positive tissues on PET/CT. In metastatic lymph nodes, the ability of PET/CT to detect cancer may depend on tumor involvement, lymph node size, and GLUT-1 expression.

The comparison of clinicopathological characteristics in primary malignant mixed mullerian tumour with epithelial endometrial carcinoma.

AIMS: We performed an age-matched case-control study to compare the clinical and pathology outcomes between histologically diagnosed primary malignant mixed mullerian tumour (MMMT) of the uterus and endometrial carcinoma. METHODS: Thirty-two women were treated for primary MMMT at seven tertiary medical centres in Korea from 2000 to 2006. For each woman with MMMT, four women with endometrioid and two with non-endometrioid endometrial carcinoma were selected as age-matched controls for analysis. Medical records were retrospectively reviewed to obtain outcome data. RESULTS: The incidence of MMMT was 2.57% (32/1244). In comparison with women with endometrioid endometrial cancer, those with MMMT were characterised by large tumour size, higher incidence of adnexal involvement and lymph node metastases, leading to advanced disease stage. Despite the frequent use of adjuvant treatment, the 5-year survival rate of women with MMMT was significantly poorer than those with endometrioid endometrial cancer. However, women with MMMT were not significantly different from those with non-endometrioid endometrial cancer in terms of important pathologic variables, apart from larger tumour size. In addition, the 5-year survival rate of women MMMT was poorer than that those with non-endometrioid endometrial cancer, but the difference was not statistically significant. CONCLUSIONS: Malignant mixed mullerian tumour is characterised by a high incidence of lymph node metastases and advanced stage at diagnosis, leading to poorer overall survival than other subtypes of endometrial carcinoma. Clinical trials for MMMT are critical for improving treatment strategies.

Efficacy of para-aortic lymphadenectomy in early-stage endometrioid uterine corpus cancer.

PURPOSE: The objective of this study was to assess whether para-aortic lymphadenectomy has therapeutic efficacy for patients with early-stage endometrioid uterine cancer who underwent systematic pelvic lymphadenectomy. METHODS: The authors retrospectively reviewed the medical records and pathological findings of 547 patients with histologically proven FIGO stage I-II endometrioid uterine cancer, based on comprehensive surgical staging, including pelvic with or without para-aortic lymphadenectomy. RESULTS: Among 547 patients, 330 patients had systematic pelvic lymphadenectomy only, and 217 had systematic pelvic with para-aortic lymphadenectomy. There were no significant differences in histopathological factors in the high-risk group, even though deep myometrial invasion (p = 0.02) and lymphvascular space invasion (p = 0.01) were more common in patients who underwent systematic pelvic with para-aortic lymphadenectomy in all study populations. Within a median follow-up of 31 (range, 5-120) months, there was no significant difference in overall survival between the pelvic lymphadenectomy only and pelvic with para-aortic lymphadenectomy groups in all populations (p = 0.77), even in high-risk patients (p = 0.82). Upon multivariate analysis, patients with lymphvascular space invasion had significantly worse overall survival (odds ratio (OR) = 7.38; 95% confidence interval (CI) = 1.86-29.23; p = 0.004). CONCLUSIONS: Although a prospective, randomized study needs to be performed for confirmation, our data suggest that the therapeutic benefit of para-aortic lymphadenectomy is uncertain in stage I and II endometrioid uterine corpus cancer, even in patients at high-risk for recurrence.

Common polymorphisms in methylenetetrahydrofolate reductase gene are associated with risks of cervical intraepithelial neoplasia and cervical cancer in women with low serum folate and vitamin B12.

OBJECTIVE: We evaluated associations between folate, vitamin B12, and the methylenetetrahydrofolate reductase (MTHFR) gene, and risk of cervical intraepithelial neoplasia (CIN) and cervical cancer. METHODS: This multicenter case-control study enrolled 927 Korean women (440 controls, 165 patients with CIN 1, 167 patients with CIN 2/3, and 155 patients with cervical cancer, aged 20-75 years). RESULTS: Patients with cervical cancer had significantly lower median serum folate and vitamin B12 concentrations vs. controls. Higher serum folate was significantly associated with lower cervical cancer risk (p for linear trend = 0.0058) with a trend for a lower CIN risk after multivariate adjustment. Low folate and the MTHFR 677 C > T variant were associated with a higher risk for CIN2/3 and cervical cancer vs. wild-type or heterozygous genotypes with high folate [OR, 2.39 (1.18-4.85) and 3.19 (1.43-7.13)]. Low vitamin B12 and the MTHFR 677 C > T variant also were associated with a higher risk for CIN 2/3 and cervical cancers [OR, 2.52 (1.17-5.42) and 2.40 (1-5.73)] vs. wild-type or heterozygous status with high vitamin levels. CONCLUSION: Serum folate concentration is inversely associated with the risk of cervical cancer, and the MTHFR variant genotype may increase CIN and cervical cancer risk in women with low folate or vitamin B12 status.

Frequent inactivation of hSRBC in ovarian cancers by promoter CpG island hypermethylation.

OBJECTIVE: To explore the implication of human SRBC gene [serum deprivation response factor-related gene product that binds to the c-kinase (hSRBC)] abnormality in ovarian tumorigenesis. DESIGN: Retrospective study. SETTING: Medical center. SAMPLE: Twenty-two epithelial ovarian cancer and six normal ovary tissues. MEASURES: Mutation and altered expression of hSRBC gene. METHODS: hSRBC expression was characterized by polymerase chain reaction (PCR) analysis. Promoter CG dinucleotide (CpG) site methylation was determined using methylation specific PCR and bisulfite sequencing. RESULTS: Expression of hSRBC transcript was easily detectable in all normal tissues we examined, but 50% (two of four) of cancer cell lines and 41% (nine of 22) of primary carcinomas exhibited undetectable or substantially decreased expression. While genomic deletion or somatic mutations of the gene was not identified, its expression was reactivated in tumor cells by 5-aza-2'-deoxycytidine treatment, suggesting epigenetic inactivation of the gene in tumors. Promoter methylation was detected in all nine tumors with low expression but in only one of 13 (7.7%) tumors with normal expression. Bisulfite DNA sequencing analysis of 23 CpG sites within the promoter region revealed that the CpG sites are highly methylated in low-expressing tumors. In addition, promoter CpG sites methylation status showed a tight association with gene expression level. CONCLUSION: Our data demonstrate that epigenetic inactivation of hSRBC due to aberrant promoter hypermethylation is a common event and might be implicated in human ovarian tumorigenesis.

Pulmonary toxicity after a quick course of combinatorial vincristine, bleomycin, and cisplatin neoadjuvant chemotherapy in cervical cancer.

Pulmonary toxicity is one of the most serious adverse effects associated with a quick course of vincristine, bleomycin, and cisplatin neoadjuvant chemotherapy (NAC-VBP). The aim of this study was to evaluate pulmonary toxicity related to a quick course NAC-VBP. A total of consecutive 61 patients, who underwent at most 3 cycles of NAC-VBP every 10 days in the International Federation of Gynecology and Obstetrics (FIGO) stage IB-IIB cervical cancer from 1995 to 2007, were retrospectively analyzed. Of the 61 study subjects, 7 (11.5%) were identified to have pulmonary toxicity and 2 (3.3%) died of pulmonary fibrosis progression despite aggressive treatment and the use of a multidisciplinary approach. No factor predisposing pulmonary toxicity was identified. Initial symptoms were non-specific, but bronchiolitis obliterans organizing pneumonia and interstitial pneumonitis were characteristic findings by high-resolution computed tomography of the chest. The benefit of steroid therapy was uncertain and was associated with steroid-induced diabetes mellitus requiring insulin therapy in two patients. Fatal pulmonary toxicity is a major concern of a quick course NAC-VBP. In conclusion, these patients require special monitoring for bleomycin-induced pulmonary toxicity.

The effects of polymorphisms in methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) on the risk of cervical intraepithelial neoplasia and cervical cancer in Korean women.

The purpose of the study was to investigate the association between cervical cancer risk and single-nucleotide polymorphisms (SNPs) in three one-carbon metabolism genes, methylenetetrahydrofolate reductase (MTHFR), methionine synthase (MTR), and methionine synthase reductase (MTRR) in Korean women. Twelve SNPs were identified in MTHFR, MTR, and MTRR in the 927 case-control samples, which included 165 cervical intraepithelial neoplasia 1 (CIN1), 167 cervical intraepithelial neoplasia 2 and 3 (CIN2/3), 155 cervical cancer patients, and 440 normal controls. The frequencies of the genotypes and haplotypes were assessed in the controls, CINs, and cervical cancers. Individual carriers of the variant allele C of MTHFR A1298C (rs1801131) had a 0.64-fold [95% confidence interval (CI): 0.42-0.98] decreased risk for CIN2/3 compared with common homozygotes. However, no significant association was found between most other variants and cervical cancer risk. The results also identified an increased CIN1 risk in carriers with at least one copy of haplotype 3 in the MTHFR gene (odds ratio, 1.88; 95% CI: 1.03-3.42). In conclusion, there was no significant association between most SNPs in MTHFR, MTR, or MTRR and the risk of CIN and cervical cancer in Korean women. In addition, there was no significant association of MTHFR haplotypes with risk of CIN2/3 and cervical cancer.

Distribution of human papillomavirus type 58 variants in progression of cervical dysplasia in Korean women.

This cross-sectional study examined the distribution of HPV 58 sequence variation in Korean women for the first time. Among 1,750 Korean women, 53 women were positive for HPV 58 single infection, of whom 26 were without disease, 20 were with cervical intraepithelial neoplasia (CIN) 1, and 7 with CIN 2 or 3. Altogether, 36 different nucleotide sequence variations were identified with the L1, 20 within E2, 5 within E6, and 10 within E7. Further studies on variants of oncogenic HPVs are necessary, particularly for the purpose of developing more predictive HPV detection methods.

Functional polymorphism in manganese superoxide dismutase and antioxidant status: their interactions on the risk of cervical intraepithelial neoplasia and cervical cancer.

OBJECTIVE: Manganese superoxide dismutase (MnSOD), the primary antioxidant enzyme in mitochondria, plays a key role in protecting cells from oxidative stress. Furthermore, the MnSOD rs4880 polymorphism is associated with enzyme activity. The authors evaluated the interaction between MnSOD genotypes and cervical carcinogenesis risk and the modulating effects of serum antioxidant nutrient status (beta-carotene, lycopene, zeaxanthin/lutein, retinol, alpha-tocopherol and gamma-tocopherol). METHODS: Cases and controls for this study were recruited between June 2006 and July 2007 (263 controls, 84 cervical intraepithelial neoplasia (CIN), 94 CIN 2/3, and 99 cases of cervical cancer). The MnSOD polymorphism at rs4880T/C was examined using SNaPshot assays. Serum antioxidant vitamin concentrations were measured by reverse-phase gradient high-pressure liquid chromatography. Odds ratios (OR) and 95% confidence intervals (95%CI) were estimated after adjusting for age, menopause, parity, oral contraceptive use, smoking and alcohol consumption. RESULTS: No association was found between the MnSOD rs4880 polymorphism and cervical cancer. However, genotypes significantly modified the risk of cervical cancer in association with the serum statuses of micronutrients (P(interaction)<0.05 for beta-carotene, lycopene, zeaxanthin/lutein, alpha-tocopherol, and gamma-tocopherol). Decreased CIN1 risk in association with the MnSOD rs4880 variant genotype was also observed particularly for subjects with higher beta-carotene and gamma-tocopherol levels. Similar results were observed for lycopene and alpha-tocopherol in relation to the risk of CIN2/3. CONCLUSION: Our findings suggest that a higher antioxidant micronutrients status may decrease the risk of CIN and cervical cancer and modify the effect of the MnSOD polymorphism on disease risk.

Expression and mutational analysis of TGF-beta/Smads signaling in human cervical cancers.

OBJECTIVE: To define the molecular basis of TGF-beta1 function in cervical carcinogenesis, we explored the expression and mutational status of TGF-beta1, TGF-beta1 receptors, and Smads, the regulators of the TGF-beta1 signaling pathway, in human cervical cancers. METHODS: Expression of TGF-beta1, TGF-beta1 receptors, and Smads transcripts were determined by quantitative reverse transcription-polymerase chain reaction (RT-PCR), and sequence alteration was analyzed using RT-PCR-single-strand conformation polymorphism (SSCP) analysis. Genomic levels of TGF-beta1, TGF-beta1 receptors and Smads was also measured by quantitative genomic PCR. RESULTS: Abnormal overexpression of TGF-beta1 and abnormal reduction of type II TGF-beta1 receptor were identified in 36% (18 of 50) and 20% (10 of 50) of cervical cancer tissues, respectively. 22% (11 of 50) in Smad2 and 14% (7 of 50) in Smad4 revealed tumor specific mRNA reduction less than a half of normal means. In addition, no evidence for sequence alterations of the gene was found by RT-PCR-SSCP analysis. CONCLUSION: Our study demonstrates that disruption of TGF-beta/Smad signaling pathway exist in human cervical cancer, suggesting that abnormal expressions of the member of TGF-beta/Smad signaling pathway might contribute to the malignant progression of human cervical tumors via suppressing the tumor suppression function of TGF-beta1 1's tumor suppression function.

Video-assisted thoracoscopic surgery for recurrent ovarian cancer with a metastatic mediastinal mass.

BACKGROUND: Although primary cytoreductive surgery is well accepted as a cornerstone of the management for epithelial ovarian cancer, the benefits of secondary cytoreduction in recurrent ovarian cancer remain unclear. Furthermore, no consensus has been reached regarding treatment strategies for extraperitoneal metastasis. CASE REPORT: A 29-year-old woman was admitted to our hospital due to suspected recurrent ovarian cancer. Four years previously, she had undergone primary debulking surgery which was followed by adjuvant chemotherapy consisting of paclitaxel (175 mg/m(2)) and carboplatin (area under the curve = 5) for 6 cycles due to an ovarian papillary serous adenocarcinoma stage IIIc. Preoperative evaluation revealed a palpable inguinal mass and multiple enlarged pelvic lymph nodes with a well-defined mediastinal mass on abdomino-pelvic and chest computed tomography. Secondary debulking combined with video-assisted thoracoscopic surgery (VATS) was performed. The patient had no discernable evidence of disease at her 18-month follow-up. CONCLUSION: VATS may be a reasonable option for secondary debulking in selected patients with isolated mediastinal metastasis.

Comparison of radiation therapy alone and concurrent chemoradiation therapy in stage III cervical cancer: a multicenter retrospective study.

OBJECTIVE: To evaluate whether concurrent chemoradiation therapy (CRT) improves overall survival as compared to radiation therapy (RT) alone in stage III cervical cancers. DESIGN: A multicenter retrospective review. SETTING: Nine tertiary medical centers in Korea. POPULATION: A total of 277 patients treated for stage III cervical cancer without para-aortic lymph node (PALN) metastasis based on clinical staging workup from 1996 to 2003. METHODS: Medical and histopathological record review. MAIN OUTCOME MEASURES: Disease-specific overall survival. RESULTS: CRT and RT alone were performed in 172 and 105 patients, respectively. There was no significant difference in disease-specific overall survival between the CRT and RT alone arms based on clinical staging workup, even though the CRT arm was characterized by younger age, more favorable performance status and lower pretreatment blood urea nitrogen level as compared to the RT alone arm. In the CRT arm, three patients succumbed to treatment-related death. CONCLUSION: CRT does not improve the overall survival rate in stage III cervical cancer as compared to RT alone based on clinical staging workup for PALN status. Special care needs to be taken regarding optimal dose and duration of RT, use of brachytherapy, anemia control and accurate pretreatment staging workup to improve survival outcome in patients with stage III cervical cancer.

Clinical characteristics of metastatic tumors to the ovaries.

Approximately 5-30% of the ovarian cancers are metastatic malignancies. The prevalence of metastatic ovarian tumors varies with the incidence rates and spread patterns of primary malignancies. We evaluated the prevalence, pre- and postoperative characteristics of metastatic ovarian cancer in Korean women. We reviewed the records for 821 ovarian malignancies with pathological consultation from 1996-2006 and recorded patient demographical, radiological, histopathological, and survival data. The study included 112 cases of histologically confirmed metastatic ovarian cancer. Metastatic ovarian cancer accounted for 13.6% of all ovarian malignancy, primarily arising from the gastrointestinal tract. The preoperative detection rate with imaging was 75%, and none of the radiological or serological features were useful for differential diagnosis. In multivariate analysis for prognostic variables, the only significant factor was the primary tumor site (p=0.004). Furthermore, extensive resection increased survival for some patients. The differential diagnosis of metastatic ovarian cancer can be problematic, so multiple diagnostic approaches are necessary. The extent of cytoreductive surgery for this type of tumor must be decided on a case-by-case basis.

Neoadjuvant chemotherapy in bulky stage IB-IIA cervical cancer: results of a quick course with vincristine, bleomycin, and cisplatin.

We retrospectively analyzed 51 consecutive patients with bulky International Federation of Gynecology and Obstetrics stage IB-IIA cervical cancer who were treated with vincristine (1 mg/m), bleomycin (25 mg/m; days 1-3), and cisplatin (50 mg/m) every 10 days between 1995 and 2005 to assess the efficacy and the safety of a quick course of neoadjuvant chemotherapy. A clinical response occurred in 37 patients (72.5%), including 7 patients (13.7%) with a complete response and 30 patients (58.8%) with a partial response; 13 patients (25.5%) had a stable disease, and 1 patient (2.0%) had a progressive disease. Among the 50 patients who were surgically explored, 42 patients had a radical hysterectomy with pelvic and para-aortic lymphadenectomy; radical surgery was aborted in 8 patients because of paracervical and para-aortic lymph node involvement. Hematologic toxicity was the most common adverse event with anemia occurring most frequently, followed by leukopenia. Importantly, pulmonary toxicity occurred in 7 patients, 2 of whom died of complications from pulmonary fibrosis 1 and 3 months after radical surgery. With a median follow-up of 53 months (range, 2-129 months), the estimated 2- and 5-year survival rates were 74.9% and 61.3%, respectively. In conclusion, the survival benefit of a quick course of neoadjuvant chemotherapy consisting of vincristine, bleomycin, and cisplatin may be uncertain despite the significant clinical response in bulky International Federation of Gynecology and Obstetrics stage IB2-IIA cervical cancer. Special care is required to monitor bleomycin-induced pulmonary toxicity.