Altered mitochondrial Ca2+ uptake in presynaptic terminals of cultured striatal and cortical neurons from the zQ175 knock-in mouse model of Huntington's disease.

Calcium (Ca2+) in mitochondria plays crucial roles in neurons including modulating metabolic processes. Moreover, excessive Ca2+ in mitochondria can lead to cell death. Thus, altered mitochondrial Ca2+ regulation has been implicated in several neurodegenerative diseases including Huntington's disease (HD). HD is a progressive hereditary neurodegenerative disorder that results from abnormally expanded cytosine-adenine-guanine trinucleotide repeats in the huntingtin gene. One neuropathological hallmark of HD is neuronal loss in the striatum and cortex. However, mechanisms underlying selective loss of striatal and cortical neurons in HD remain elusive. Here, we measured the basal Ca2+ levels and Ca2+ uptake in single presynaptic mitochondria during 100 external electrical stimuli using highly sensitive mitochondria-targeted Ca2+ indicators in cultured cortical and striatal neurons of a knock-in mouse model of HD (zQ175 mice). We observed elevated presynaptic mitochondrial Ca2+ uptake during 100 electrical stimuli in HD cortical neurons compared with wild-type (WT) cortical neurons. We also found the highly elevated presynaptic mitochondrial basal Ca2+ level and Ca2+ uptake during 100 stimuli in HD striatal neurons. The elevated presynaptic mitochondrial basal Ca2+ level in HD striatal neurons and Ca2+ uptake during stimulation in HD striatal and cortical neurons can disrupt neurotransmission and induce mitochondrial Ca2+ overload, eventually leading to neuronal death in the striatum and cortex of HD.

Altered anterograde axonal transport of mitochondria in cultured striatal neurons of a knock-in mouse model of Huntington's disease.

Huntington's disease (HD) is a progressive genetic neurodegenerative disease caused by an abnormal expansion of a cytosine-adenine-guanine trinucleotide repeat in the huntingtin gene. One pathological feature of HD is neuronal loss in the striatum. Despite many efforts, mechanisms underlying neuronal loss in HD striatum remain elusive. It was suggested that the mutant huntingtin protein interacts mitochondrial proteins and causes mitochondrial dysfunction in striatal neurons. However, whether axonal transport of mitochondria is altered in HD striatal neurons remains controversial. Here, we examined axonal transport of single mitochondria labelled with Mito-DsRed2 in cultured striatal neurons of zQ175 knock-in mice (a knock-in mouse model of HD). We observed decreased anterograde axonal transport of proximal mitochondria in HD striatal neurons compared with wild-type (WT) striatal neurons. Decreased anterograde transport in HD striatal neurons was prevented by overexpressing mitochondrial Rho GTPase 1 (Miro1). Our results offer a new insight into mechanisms underlying neuronal loss in the striatum in HD.

Time from Exposure to Diagnosis among Quarantined Close Contacts of SARS-CoV-2 Omicron Variant Index Case-Patients, South Korea.

To determine optimal quarantine duration, we evaluated time from exposure to diagnosis for 107 close contacts of severe acute respiratory syndrome coronavirus 2 Omicron variant case-patients. Average time from exposure to diagnosis was 3.7 days; 70% of diagnoses were made on day 5 and 99.1% by day 10, suggesting 10-day quarantine.

Importation and Transmission of SARS-CoV-2 B.1.1.529 (Omicron) Variant of Concern in Korea, November 2021.

In November 2021, 14 international travel-related severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) B.1.1.529 (omicron) variant of concern (VOC) patients were detected in South Korea. Epidemiologic investigation revealed community transmission of the omicron VOC. A total of 80 SARS-CoV-2 omicron VOC-positive patients were identified until December 10, 2021 and 66 of them reported no relation to the international travel. There may be more transmissions with this VOC in Korea than reported.

Simultaneous tracking of two motor domains reveals near simultaneous steps and stutter steps of myosin 10 on actin filament bundles.

Myosin X (Myo10) has several unique design features including dimerization via an anti-parallel coiled coil and a long lever arm, which allow it to preferentially move on actin bundles. To understand the stepping behavior of single Myo10 on actin bundles, we labeled two heads of Myo10 dimers with different fluorophores. Unlike previously described for myosin V (Myo5) and VI (Myo6), which display alternating hand-over-hand stepping, Myo10 frequently took near simultaneous steps of both heads, and less frequently, 2-3 steps of one head before the other head stepped. We suggest that this behavior results from the unusual kinetic features of Myo10, in conjunction with the structural properties of the motor domain/lever arm, which will favor movement on actin bundles rather than on single filaments.

Prognostic impact of synchronous second primary malignancies on the overall survival of patients with metastatic prostate cancer.

PURPOSE: We determined the prognostic impact of a synchronous second primary malignancy on overall survival in patients with metastatic prostate cancer. Identifying features that stratify the risk of overall survival is critical for judiciously applying definitive therapy. MATERIALS AND METHODS: We retrospectively analyzed the records of 582 consecutive patients with prostate cancer diagnosed with metastasis between May 7, 1998 and August 27, 2011. Patient age, body mass index, ECOG performance status, Charlson comorbidity index, prostate specific antigen, T and N stages, Gleason and ASA® scores, progression to castration resistant prostate cancer, prior local treatments and synchronous second primary malignancies at metastasis were assessed. A synchronous second primary malignancy was defined as a cytologically or histologically proven solid malignancy. Cox proportional hazards regression analysis was done to estimate overall survival by second primary type and evaluate predictive variables. RESULTS: A total of 164 patients (28.1%) had a synchronous second primary malignancy, of which colorectal (9.1%), stomach (7.3%) and lung (7.1%) cancers were the most prevalent types. During a median followup of 34.1 months patients without a synchronous second primary malignancy had a significantly higher overall survival rate than those with lung or stomach cancer. However, men without a second malignancy had outcomes comparable to those in men with colorectal cancer. Clinical stage T4 or greater, ASA score 1 or greater and lung or stomach cancer were independent predictors of overall mortality. CONCLUSIONS: A substantial proportion of patients with metastatic prostate cancer present with a synchronous second primary malignancy. Definitive therapy targeting prostate cancer may confer a limited survival benefit in patients with synchronous lung or stomach cancer.

External validation of the RENAL nephrometry score nomogram for predicting high-grade renal cell carcinoma in solid, enhancing, and small renal masses.

PURPOSE: To confirm predictive accuracies of the RENAL nephrometry score (RNS) nomogram for identifying malignancy and high-grade renal cell carcinoma (RCC) in an external cohort of small renal masses (SRMs). METHODS: A total of 1,129 patients who underwent extirpative renal surgery for solid and enhancing cT1 renal tumors between 2005 and 2012 at a single institution were included in the validation cohort. A single uro-radiologist utilized computed tomography image reconstruction to classify tumors according to the RNS. The area under the curve (AUC) and calibration plots were used to determine predictive accuracies of malignancy and high-grade models of the RNS nomogram. RESULTS: Malignant and high-grade tumors were identified in 1,012 (89.6%) and 389 (38.4%) patients with cT1 tumors, and in 658 (87.3%) and 215 (32.6%) patients with cT1a tumors, respectively. Predictive performances of the nomogram for malignancy and high-grade models revealed AUCs of 0.722 and 0.574 for cT1 tumors, and 0.727 and 0.495 for cT1a tumors, respectively. The predictive value of the malignancy model was comparable to that of the model-development cohort (AUC = 0.76); however, the predictive value of the high-grade model was inferior to that of the model-development cohort (AUC = 0.73). CONCLUSIONS: Unlike previous validation studies, we report inferior predictive performance of the RNS nomogram for discriminating high-grade RCC in solid and enhancing SRMs. This suggests that the RNS nomogram may be unreliable for preoperatively predicting high-grade RCC in SRMs, in which tumor size, the key determinant of high-grade RCC, is a limiting factor.

Risk factors for SARS-CoV-2 transmission during a movie theater outbreak in Incheon in the Republic of Korea, November 2021: a retrospective study.

BACKGROUND: We examined factors contributing to the transmission of an acute respiratory virus within multi-use facilities, focusing on an outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a movie theater in the Republic of Korea. METHODS: This retrospective cohort study involved a descriptive analysis of 48 confirmed cases. Logistic regression was applied to a cohort of 80 theater attendees to identify risk factors for infection. The infection source and transmission route were determined through gene sequencing data analysis. RESULTS: Of the 48 confirmed cases, 35 were theater attendees (72.9%), 10 were family members of attendees (20.8%), 2 were friends (4.2%), and 1 was an employee (2.1%). Among the 80 individuals who attended the 3rd to 5th screenings of the day, 35 became infected, representing a 43.8% attack rate. Specifically, 28 of the 33 third-screening attendees developed confirmed SARSCoV-2, constituting an 84.8% attack rate. Furthermore, 11 of the 12 cases epidemiologically linked to the theater outbreak were clustered monophyletically within the AY.69 lineage. At the time of the screening, 35 individuals (72.9%) had received 2 vaccine doses. However, vaccination status did not significantly influence infection risk. Multivariate analysis revealed that close contacts had a 15.9-fold higher risk of infection (95% confidence interval, 4.37-78.39) than casual contacts. CONCLUSION: SARS-CoV-2 transmission occurred within the theater, and extended into the community, via a moviegoer who attended the 3rd screening during the viral incubation period after contracting the virus from a family member. This study emphasizes the importance of adequate ventilation in theaters.

Altered exocytosis of inhibitory synaptic vesicles at single presynaptic terminals of cultured striatal neurons in a knock-in mouse model of Huntington's disease.

Huntington's disease (HD) is a progressive dominantly inherited neurodegenerative disease caused by the expansion of a cytosine-adenine-guanine (CAG) trinucleotide repeat in the huntingtin gene, which encodes the mutant huntingtin protein containing an expanded polyglutamine tract. One of neuropathologic hallmarks of HD is selective degeneration in the striatum. Mechanisms underlying selective neurodegeneration in the striatum of HD remain elusive. Neurodegeneration is suggested to be preceded by abnormal synaptic transmission at the early stage of HD. However, how mutant huntingtin protein affects synaptic vesicle exocytosis at single presynaptic terminals of HD striatal neurons is poorly understood. Here, we measured synaptic vesicle exocytosis at single presynaptic terminals of cultured striatal neurons (mainly inhibitory neurons) in a knock-in mouse model of HD (zQ175) during electrical field stimulation using real-time imaging of FM 1-43 (a lipophilic dye). We found a significant decrease in bouton density and exocytosis of synaptic vesicles at single presynaptic terminals in cultured striatal neurons. Real-time imaging of VGAT-CypHer5E (a pH sensitive dye conjugated to an antibody against vesicular GABA transporter (VGAT)) for inhibitory synaptic vesicles revealed a reduction in bouton density and exocytosis of inhibitory synaptic vesicles at single presynaptic terminals of HD striatal neurons. Thus, our results suggest that the mutant huntingtin protein decreases bouton density and exocytosis of inhibitory synaptic vesicles at single presynaptic terminals of striatal neurons, causing impaired inhibitory synaptic transmission, eventually leading to the neurodegeneration in the striatum of HD.

The hsa-miR-5787 represses cellular growth by targeting eukaryotic translation initiation factor 5 (eIF5) in fibroblasts.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate diverse biological processes. We cloned novel small RNA from human mesenchymal stem cells (hMSCs) and termed microRNA-5787 (hsa-miR-5787) that met the criteria for a miRNA. The level of miR-5787 was elevated in senescent fibroblasts. Based on the target prediction algorithm and results that were obtained, we find that eukaryotic translation initiation factor 5 (eIF5) is a target of miR-5787. Similar to the over-expression of miR-5787, we showed that repression of eIF5 in fibroblasts negatively affected cell growth. Therefore, we propose that the miR-5787 represses cell growth, in part, by targeting eIF5.

Real-time three-dimensional tracking of single vesicles reveals abnormal motion and pools of synaptic vesicles in neurons of Huntington's disease mice.

Although defective synaptic transmission was suggested to play a role in neurodegenerative diseases, the dynamics and vesicle pools of synaptic vesicles during neurodegeneration remain elusive. Here, we performed real-time three-dimensional tracking of single synaptic vesicles in cortical neurons from a mouse model of Huntington's disease (HD). Vesicles in HD neurons had a larger net displacement and radius of gyration compared with wild-type neurons. Vesicles with high release probability (Pr) were interspersed with low-Pr vesicles in HD neurons, whereas high-Pr vesicles were closer to fusion sites than low-Pr in wild-type neurons. Non-releasing vesicles in HD neurons had an abnormally high prevalence of irregular oscillatory motion. These abnormal dynamics and vesicle pools were rescued by overexpressing Rab11, and the abnormal irregular oscillatory motion was rescued by jasplakinolide. Our studies reveal the abnormal dynamics and pools of synaptic vesicles in the early stages of HD, suggesting a possible pathogenic mechanism of neurodegenerative diseases.

Usefulness of non-invasive markers for predicting significant fibrosis in patients with chronic liver disease.

The purpose of this prospective study was to verify and compare the strengths of various blood markers and fibrosis models in predicting significant liver fibrosis. One hundred fifty-eight patients with chronic liver disease who underwent liver biopsy were enrolled. The mean age was 41 yr and male patients accounted for 70.2%. The common causes of liver disease were hepatitis B (67.7%) and C (16.5%) and fatty liver (9.5%). Stages of liver fibrosis (F0-4) were assessed according to the Batts and Ludwig scoring system. Significant fibrosis was defined as > or =F2. Sixteen blood markers were measured along with liver biopsy, and estimates of hepatic fibrosis were calculated using various predictive models. Predictive accuracy was evaluated with a receiver-operating characteristics (ROC) curve. Liver biopsy revealed significant fibrosis in 106 cases (67.1%). On multivariate analysis, alpha2-macroglobulin, hyaluronic acid, and haptoglobin were found to be independently related to significant hepatic fibrosis. A new predictive model was constructed based on these variables, and its area under the ROC curve was 0.91 (95% confidence interval, 0.85-0.96). In conclusion, alpha2-macroglobulin, hyaluronic acid, and haptoglobin levels are independent predictors for significant hepatic fibrosis in chronic liver disease.

Alteration of microRNA 340-5p and Arginase-1 Expression in Peripheral Blood Cells during Acute Ischemic Stroke.

Acute stroke alters the systemic immune response as can be observed in peripheral blood; however, the molecular mechanism by which microRNA (miRNA) regulates target gene expression in response to acute stroke is unknown. We performed a miRNA microarray on the peripheral blood of 10 patients with acute ischemic stroke and 11 control subjects. Selected miRNAs were quantified using a TaqMan assay. After searching for putative targets from the selected miRNAs using bioinformatic analysis, functional studies including binding capacity and protein expression of the targets of the selected miRNAs were performed. The results reveal a total of 30 miRNAs that were differentially expressed (16 miRNAs were upregulated and 14 miRNAs were downregulated) during the acute phase of stroke. Using prediction analysis, we found that miR-340-5p was predicted to bind to the 3'-untranslated region of the arginase-1 (ARG1) gene; a luciferase reporter assay confirmed the binding of miR-340-5p to ARG1. miR-340-5p was downregulated whereas ARG1 mRNA was upregulated in peripheral blood in patients experiencing acute stroke. Overexpression of miR-340-5p in human neutrophil and mouse macrophage cell lines induced downregulation of the ARG1 protein. Transfection with miR-340-5p increased nitric oxide production after LPS treatment in a mouse macrophage cell line. Our results suggest that several miRNAs are dynamically altered in the peripheral blood during the acute phase of ischemic stroke, including miR-340-5p. Acute stroke induces the downregulation of miR-340-5p, which subsequently upregulates ARG1 protein expression.

Evaluation of the prognostic powers of various tumor status grading scales in patients with hepatocellular carcinoma.

BACKGROUNDS AND AIM: Several tumor status grading scales are available for patients with hepatocellular carcinoma (HCC), which include several tumor-node-metastasis (TNM) systems and clinical staging systems, such as Cancer of the Liver Italian Program (CLIP) and Barcelona Clinic Liver Cancer (BCLC). This study was performed to analyze the prognostic powers of these tumor status grading systems in HCC. METHODS: A retrospective cohort of 499 consecutive patients with HCC was included. The tumor statuses of all patients were classified according to several TNM systems (sixth version of the American Joint Committee on Cancer, fourth version of the Liver Cancer Study Group of Japan [LCSGJ], and the United Network for Organ Sharing UNOS system) and according to the tumor status grading scales of the BCLC (TBCLC) and CLIP (TCLIP) systems. Prognostic powers were quantified using a linear trend chi(2)-test, c-index, and the likelihood ratio (LHR) chi(2)-test, and correlated using Cox's regression model adjusted using the Akaike information criterion (AIC). RESULTS: Of the TNM systems, the fourth LCSGJ system had the highest prognostic power (LHR chi(2) = 7.20, AIC = 4803.02). However, when TBCLC and TCLIP were included in the analysis, TCLIP showed the best predictive power (LHR chi(2) = 29.52, AIC = 4799.82). CONCLUSION: TCLIP had best predictive power in HCC patients of the various tumor staging systems examined. To improve prognostic power, factors other than tumor burden, such as tumor behavior, should be included in the tumor status grading system for HCC.

Decreased BDNF Release in Cortical Neurons of a Knock-in Mouse Model of Huntington's Disease.

Huntington's disease (HD) is a dominantly inherited neurodegenerative disease caused by an increase in CAG repeats in the Huntingtin gene (HTT). The striatum is one of the most vulnerable brain regions in HD, and altered delivery of BDNF to the striatum is believed to underlie this high vulnerability. However, the delivery of BDNF to the striatum in HD remains poorly understood. Here, we used real-time imaging to visualize release of BDNF from cortical neurons cultured alone or co-cultured with striatal neurons. BDNF release was significantly decreased in the cortical neurons of zQ175 mice (a knock-in model of HD), and total internal reflection fluorescence microscopy revealed several release patterns of single BDNF-containing vesicles, with distinct kinetics and prevalence, in co-cultured cortical HD neurons. Notably, a smaller proportion of single BDNF-containing vesicles underwent full release in HD neurons than in wild-type neurons. This decreased release of BDNF in cortical neurons might lead to decreased BDNF levels in the striatum because the striatum receives BDNF mainly from the cortex. In addition, we observed a decrease in the total travel length and speed of BDNF-containing vesicles in HD neurons, indicating altered transport of these vesicles in HD. Our findings suggest a potential mechanism for the vulnerability of striatal neurons in HD and offer new insights into the pathogenic mechanisms underlying the degeneration of neurons in HD.

Surgical thyroparathyroidectomy prevents progression of 5TGM1 murine multiple myeloma in vivo.

The 5TGM1 multiple myeloma transplanted C57BL6/KaLwRij model recapitulates many disease features including monoclonal paraprotein production as well as the development of osteolytic bone lesions. Since a significant association between serum parathyroid hormone PTH variations, bone anabolism and myeloma progression in patients receiving proteasome inhibitors exists, this study investigated the effect of the PTH axis on murine myeloma development in vivo. C57BL6/KaLwRij myeloma-bearing mice underwent thyroparathyroidectomy (TPTX) before and after 5TGM1 cell transplantation. TPTX significantly and permanently inhibited 5TGM1 myeloma cell engraftment and prevented multiple myeloma growth and progression. These data support the hypothesis that the PTH axis is an important mediator of myeloma bone disease.

Thymic PTH Increases After Thyroparathyroidectomy in C57BL/KaLwRij Mice.

We previously reported a substantial correlation between serum parathyroid hormone (PTH) levels and the myeloma response to proteasome inhibition that suggests a crucial role for the PTH receptor 1 system in the control of myeloma tumor growth. While investigating the role of PTH in the antimyeloma effect, we observed the recovery of serum PTH levels after thyroparathyroidectomy (TPTX). Although the presence of thymus-derived PTH has been reported previously, the existence or role of thymic PTH in the serum remains controversial. Here, TPTX was performed in 8- to 12-week-old C57BL/KaLwRij mice to delineate the potential source(s) for the recovery of serum PTH. Immediately after TPTX, the expected loss of measurable serum PTH was observed. Serum PTH levels recovered 3 to 4 weeks after TPTX. Thirteen endocrine organs from mice with recovered serum PTH were examined. The thymus from control mice expressed measurable and detectable Pth transcripts; however, the Pth transcript level was substantially elevated in tissue from TPTX mice. Western blot analysis of the thymus demonstrated a reproducible and distinct PTH band in thymus tissue that was significantly increased after TPTX. To directly confirm the identity of the distinct PTH band, immunoprecipitated proteins were isolated and subjected to tandem mass spectrometry. After fragmentation and direct peptide sequencing, PTH peptides PTH(1-13) and PTH(54-70), diagnostic for PTH, were identified. These data demonstrate that the murine thymus produces PTH and that after TPTX the thymus becomes the major source of serum PTH, compensating for the loss of the parathyroid glands and returning circulating PTH levels to normal.

Comparison of the i-gel and other supraglottic airways in adult manikin studies: Systematic review and meta-analysis.

BACKGROUND: The i-gel has a gel-like cuff composed of thermoplastic elastomer that does not require cuff inflation. As the elimination of cuff inflation may shorten insertion time, the i-gel might be a useful tool in emergency situations requiring prompt airway care. This systematic review and meta-analysis of previous adult manikin studies for inexperienced personnel was performed to compare the i-gel with other supraglottic airways. METHODS: We searched PubMed, the Cochrane Library, and EMBASE for eligible randomized controlled trials (RCTs) published before June 2015, including with a crossover design, using the following search terms: "i-gel," "igel," "simulation," "manikin," "manikins," "mannequin," and "mannequins." The primary outcomes of this review were device insertion time and the first-attempt success rate of insertion. RESULTS: A total of 14 RCTs were included. At the initial assessment without difficult circumstances, the i-gel had a significantly shorter insertion time than the LMA Classic, LMA Fastrach, LMA Proseal, LMA Unique, laryngeal tube, Combitube, and EasyTube. However, a faster insertion time of the i-gel was not observed in comparisons with the LMA Supreme, aura-i, and air-Q. In addition, the i-gel did not show the better results for the insertion success rate when compared to other devices. CONCLUSION: The findings of this meta-analysis indicated that inexperienced volunteers placed the i-gel more rapidly than other supraglottic airways with the exception of the LMA Supreme, aura-i, and air-Q in manikin studies. However, the quicker insertion time is clinically not relevant. The unapparent advantage regarding the insertion success rate and the inherent limitations of the simulation setting indicated that additional evidence is necessary to confirm these advantages of the i-gel in an emergency setting.

Retinal Nerve Fiber Layer Thickness is Decreased in Patients With Hematologic Malignancy.

PURPOSE: To investigate whether retinal nerve fiber layer (RNFL) thickness is decreased in patients with hematologic malignancy using optical coherence tomography (OCT). PATIENTS AND METHODS: This prospective, observational cross-sectional study included 65 eyes from 34 patients with hematologic malignancy and 72 healthy control eyes. OCT-measured RNFL thickness parameters (average, 4 quadrants, and 12 clock-hour thickness) and RNFL defect in red-free photo were compared between patients with hematologic malignancy and controls. RESULTS: Among average, quadrant, and clock-hour map, the only 11-o'clock RNFL in patients with hematologic malignancy was statistically thinner than in controls (P=0.021). The RNFL defect was detected in 21/65 (32.3%) patients with hematologic malignancy and in 5/72 (6.9%) controls (P<0.001). In patients with hematologic malignancy, the mean RNFL thickness was significantly lower in the severe and moderate anemia groups compared with the mild anemia group (P=0.011). In the generalized estimating equations model, the mean hemoglobin level was associated with RNFL thickness while correcting for inter-eye correlation, age, and refraction error (coefficient=3.685, P=0.006). CONCLUSIONS: The RNFL defect was frequently observed, and the RNFL was thinner in severe anemic patients with hematologic malignancy. These results suggest that chronic anemia may be a factor of RNFL loss.

Clinical Significance of CA125 Level after the First Cycle of Chemotherapy on Survival of Patients with Advanced Ovarian Cancer.

PURPOSE: To determine the most powerful cancer antigen 125 (CA125)-related prognostic factor for advanced epithelial ovarian cancer (EOC) and to identify cut-off values that distinguish patients with a poor prognosis from those with a good prognosis. MATERIALS AND METHODS: We included 223 patients who received staging laparotomy and were diagnosed with stage IIC-IV serous EOC. Cox regression analysis was used to determine the most significant prognostic factor among the following variables: serum CA125 before surgery and after the first, second, and sixth cycles of chemotherapy; the nadir CA125 value; the relative percentage change in CA125 levels after the first and second cycles of chemotherapy compared to baseline CA125; CA125 half-life; time to nadir; and time to normalization of the CA125 level. RESULTS: The CA125 level after the first chemotherapy cycle was the most significant independent prognostic factor for overall survival (OS). Time to normalization (p=0.028) and relative percentage change between CA125 levels at baseline and after the first chemotherapy cycle (p=0.021) were additional independent prognostic factors in terms of OS. The CA125 level after the first chemotherapy cycle (p=0.001) and time to normalization (p<0.001) were identified as independent prognostic factors for progression free survival (PFS). CONCLUSION: Among well-established CA125-related prognostic factors, serum CA125 levels after the first cycle of chemotherapy and time to normalization were the most significant prognostic factors for both OS and PFS.