High-dose (60 Gy) intensity-modulated radiotherapy with concurrent weekly cisplatin followed by intracavitary radiation in locally advanced cervical cancer: A phase II prospective clinical trial.

OBJECTIVE: Radiotherapy dose-escalation using intensity-modulated radiotherapy (IMRT) has been necessary to improve treatment results in cervical cancer. METHODS: This was a phase II prospective clinical trial. 88 patients with FIGO II-IVa cervical cancer were enrolled in a single center. They received high-dose (60 Gy) IMRT with weekly cisplatin to the primary tumor and clinically positive nodes followed by intracavitary radiation. The primary endpoint was 30-month PFS rate (Target; 82%, an increase of 20% compared to GOG 120 trial using standard-dose radiotherapy). Secondary endpoints were tumor response, toxicity, recurrence, distant metastasis, and overall survival. RESULTS: Progression-free survival rate at 30 months was 82.8%. Overall survival, locoregional recurrence, distant metastasis, and para-aortic recurrence rates at 30 months were 93.6%, 8.2%, 9.2%, and 2.4%, respectively. Forty-five (51.1%) of 88 patients achieved downstaging on MRI during radiotherapy and 80 (90.9%) patients had clinically complete response at three months after high-dose IMRT and intracavitary radiotherapy. The 30-month recurrence-free survival (92.9% vs. 73.1%, P = 0.009) and overall survival (100% vs. 87.0%, P = 0.006) were significantly higher in the downstaged group than in the non-downstaged group during radiotherapy. Grade 3 or higher hematologic toxicity was found in 11 (12.5%) patients and grade 3 or higher non-hematologic toxicity was found in 3 (3.4%) patients. Fourteen had chronic urinary (8.0%), intestinal (5.7%) toxicity, pelvic insufficiency fracture (2.3%) or vesicovaginal fistula (2.3%). CONCLUSION: High-dose (60 Gy) IMRT with concurrent weekly cisplatin in locally advanced cervical cancer yielded favorable progression-free survival outcome. Tumor response during radiotherapy can be a significant prognostic factor for PFS. CLINICAL TRIAL INFORMATION: This prospective trial is registered at ClinicalTrials.gov Identifier: NCT02993653.

Association Between Hamstring Shortness and Asymmetry, Pain Intensity, Disability Index, and Compensatory Lumbar Movement in 60 Patients with Nonspecific Chronic Low Back Pain.

BACKGROUND The correlation between hamstring muscle shortening and nonspecific low back pain and compensatory lumbar movements is still controversial. The purpose of this study was to evaluate the association between hamstring shortness and asymmetry, pain intensity, the disability index, and compensatory lumbar movement in 60 patients with nonspecific chronic low back pain. MATERIAL AND METHODS Sixty patients with nonspecific low back pain participated in this study. The hamstring shortness and asymmetry, pain intensity, the disability index, and compensatory lumbar movement of the patients were assessed. The pain intensity was evaluated using a numeric pain rating scale (NPRS), active knee extension testing was performed to measure the length of the hamstring, and compensatory lumbar movement was assessed using a digital dual inclinometer. Correlation analysis was used for analysis of the obtained data. RESULTS The hamstring length showed a negative correlation with hamstring length asymmetry, NPRS, and disability index (P<0.05). The asymmetry of the hamstring length was positively correlated with NPRS, disability index, and compensatory lumbar rotation (P<0.05). Lumbar flexion was positively correlated with the hamstring muscle length (P<0.05). However, there was a negative correlation between the hamstring length asymmetry, NPRS, and disability index (P<0.05). There was no correlation between the compensatory lumbar rotation, hamstring length, or disability index. CONCLUSIONS Compensatory flexion movements, NPRS, and disability index in patients with nonspecific chronic low back pain were associated with hamstring shortness and asymmetry. These factors should be considered when planning physical therapy for patients with nonspecific low back pain.

Comparison of compensatory lumbar movement in participants with and without non-specific chronic low back pain: A cross-sectional study.

BACKGROUND: Many studies have compared muscle length and muscle activity for low back pain. However, compensatory movement for non-specific low back pain has not yet been studied sufficiently. OBJECTIVE: The purpose of this study was to compare the length of the hip flexor, lumbar extensor endurance and the muscle activity of the erector spinae and gluteus maximus during hip extension, and the compensatory movement of the lumbar in people with or without nonspecific chronic low back pain. METHODS: In this case-control study, 16 participants with non-specific chronic LBP and 17 without LBP were included. Hip flexor length was assessed by the modified Thomas test. Lumbar extensor endurance was assessed by the modified Biering-Sorensen test. Muscle activity of the erector spinae and gluteus maximus during hip extension was measured using a Delsys-Trigno wireless EMG system. Compensatory lumbar movements during hip extension were measured using a digital inclinometer. RESULTS: Muscle activity of the erector spinae and compensatory lumbar movements were significantly higher in the LBP group. (p< 0.05). Hip flexor length, muscle activity of the gluteus maximus and endurance of the lumbar extensor were significantly differences in the LBP group (p< 0.05). CONCLUSIONS: Shortened hip flexors, low gluteus maximus activity, and high erector spinae activity during hip extension, lumbar extensor weak endurance, lumbar compensatory movement are potential factors for non-specific LBP.

Identification of candidate biomarkers using the Experion™ automated electrophoresis system in serum samples from ovarian cancer patients.

Ovarian cancer is the most common cause of disease-related death in women globally. Detection of ovarian cancer using new biomarkers is necessary for early diagnosis. To date, there have been no obvious biomarkers for ovarian cancer detection in the incipient stage. In this study, we discovered potential diagnostic serological biomarkers for ovarian cancer using the Experion™ automated electrophoresis system. Sera from 14 healthy women and 84 ovarian cancer patients at stages I- IV were applied to the Experion to compare the protein expression levels. To examine the protein expression pattern of Experion data, proteins in the samples were resolved using 10 and 15% sodium dodecyl sulfate-polyacrylamide gel electrophoresis and visualized by silver staining. The candidate biomarkers elevated in ovarian cancer were purified and determined using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. α-2-macroglobulin (173.7 kDa), ceruloplasmin (147 kDa), inter-α-trypsin inhibitor family heavy chain-related protein (126 kDa), C-1 inhibitor (115.2 kDa) and hemoglobin α/ß (14.4 kDa were overexpressed in the ovarian cancer sera. This study documents a novel way to measure ovarian cancer or cancer-related proteins for biomarkers using the Experion assay system, which should be easily adaptable for high-throughput diagnosis to establish databases of ovarian cancer for clinical applications.

Comparison of single-, double- and triple-combined testing, including Pap test, HPV DNA test and cervicography, as screening methods for the detection of uterine cervical cancer.

Cervical cancer is a serious disease that threatens the health of women worldwide. This study compared the sensitivities and false-positive rates of cervical cytology (Pap smear), human papilloma virus (HPV) DNA test, cervicography, first double-combined testing (cervical cytology and HPV DNA test), second double-combined testing (cervical cytology and cervicography) and triple-combined testing (cervical cytology, HPV DNA test and cervicography). The study included 261 patients screened for uterine cervical cancer. All women simultaneously underwent cervical cytology, HPV DNA test and cervicography for uterine cervical cancer screening and colposcopically directed biopsy for diagnostic evaluation. The triple-combined testing was consistently the most sensitive among the cervical screening tests. The second double-combined testing, with a sensitivity rate of 98.1% was more sensitive than the first double-combined test (92.3%). However, cervical cytology was most specific (93.5%) and showed the highest positive predictive value (77.8%). The sensitivity of cervical cytology was markedly improved in combination with HPV DNA test and cervicography. Thus, the triple-combined testing, which improves the high false negativity of cervical cytology, may be an effective tool in uterine cervical cancer screening, pending confirmation of the effectiveness in a mass screening study.

Analysis of molecular cytogenetic alterations in uterine leiomyosarcoma by array-based comparative genomic hybridization.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Cell cycle regulatory protein expression profiles by adenovirus p53 infection in human papilloma virus-associated cervical cancer cells.

PURPOSE: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.