Publications by authors named "Nam-Kyung Lee"

117 Publications

Inadequate Ultrasound Examination in Hepatocellular Carcinoma Surveillance: A Systematic Review and Meta-Analysis.

J Clin Med 2021 Aug 12;10(16). Epub 2021 Aug 12.

Department of Radiology, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, 222 Banpo-daero, Seocho-gu, Seoul 06591, Korea.

We aimed to systematically evaluate the incidence of inadequate US in hepatocellular carcinoma (HCC) surveillance and determine the risk factors. Original studies reporting the incidence or risk factors for inadequate US were identified in MEDLINE, EMBASE, and the Cochrane database. The pooled incidence of inadequate US was calculated using a random effects model, and subgroup analyses were performed. The pooled odds ratio (OR) was calculated for each risk factor for inadequate US. Six eligible articles were identified from 756 screened articles (4250 patients). The pooled incidence of inadequate US was 21.5%. Significantly higher rates of inadequate US were noted in studies including patients with and without hepatic observations compared with those evaluating only patients with hepatic observations (23.2% vs. 18.8%), studies using US alone compared with US plus alpha-fetoprotein (28.0% vs. 20.8%), and those using pathology and imaging as a reference standard compared with imaging only (23.2% vs. 17.9%). Nonalcoholic steatohepatitis (OR = 2.3 (1.07-4.84)), Child-Pugh B cirrhosis (OR = 2.2 (1.10-4.37)), and high body mass index (OR = 2.2 (1.12-4.24)) were significant risk factors for inadequate US ( ≤ 0.04). In patients at risk of HCC, 21.5% of US surveillance was inadequate. An alternative surveillance modality might be considered in patients with risk factors.
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http://dx.doi.org/10.3390/jcm10163535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8397222PMC
August 2021

Characterization of breast cancer subtypes based on quantitative assessment of intratumoral heterogeneity using dynamic contrast-enhanced and diffusion-weighted magnetic resonance imaging.

Eur Radiol 2021 Aug 4. Epub 2021 Aug 4.

Busan Cancer Center, Pusan National University Hospital, Busan, Republic of Korea.

Objective: To investigate whether intratumoral heterogeneity, assessed via dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and diffusion-weighted imaging (DWI), reflects the molecular subtypes of invasive breast cancers.

Material And Methods: We retrospectively evaluated data from 248 consecutive women (mean age ± standard deviation, 54.6 ± 12.2 years) with invasive breast cancer who underwent preoperative DCE-MRI and DWI between 2019 and 2020. To evaluate intratumoral heterogeneity, kinetic heterogeneity (a measure of heterogeneity in the proportions of tumor pixels with delayed washout, plateau, and persistent components within a tumor) was assessed with DCE-MRI using a commercially available computer-aided diagnosis system. Apparent diffusion coefficients (ADCs) were obtained using a region-of-interest technique, and ADC heterogeneity was calculated using the following formula: (ADC-ADC)/ADC. Possible associations between imaging-based heterogeneity values and breast cancer subtypes were analyzed.

Results: Of the 248 invasive breast cancers, 61 (24.6%) were classified as luminal A, 130 (52.4%) as luminal B, 25 (10.1%) as HER2-enriched, and 32 (12.9%) as triple-negative breast cancer (TNBC). There were significant differences in the kinetic and ADC heterogeneity values among tumor subtypes (p < 0.001 and p = 0.023, respectively). The TNBC showed higher kinetic and ADC heterogeneity values, whereas the HER2-enriched subtype showed higher kinetic heterogeneity values compared to the luminal subtypes. Multivariate linear analysis showed that the HER2-enriched (p < 0.001) and TNBC subtypes (p < 0.001) were significantly associated with higher kinetic heterogeneity values. The TNBC subtype (p = 0.042) was also significantly associated with higher ADC heterogeneity values.

Conclusions: Quantitative assessments of heterogeneity in enhancement kinetics and ADC values may provide biological clues regarding the molecular subtypes of breast cancer.

Key Points: • Higher kinetic heterogeneity was associated with HER2-enriched and triple-negative breast cancer. • Higher ADC heterogeneity was associated with triple-negative breast cancer. • Aggressive breast cancer subtypes exhibited higher intratumoral heterogeneity based on MRI.
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http://dx.doi.org/10.1007/s00330-021-08166-4DOI Listing
August 2021

Puncture needle with a hard plastic sheath and plastic wings minimizes repuncture attempts in ultrasound-guided paracentesis.

Yeungnam Univ J Med 2021 Jul 12. Epub 2021 Jul 12.

Department of Internal Medicine, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea.

Background: This study was performed to evaluate periprocedural factors, complications, and repuncture rate of the newly developed puncture needle and compare it with the routinely used puncture needle for ultrasound (US)-guided paracentesis.

Methods: We retrospectively identified 137 patients who underwent US-guided paracentesis between July 2018 and March 2019. Among them, 82 patients underwent US-guided paracentesis with a newly developed puncture needle. The other 55 patients underwent US-guided paracentesis with a routinely used puncture needle. The periprocedural factors, complications, and repuncture rate were compared between the two groups using the Mann-Whitney U test and Fisher exact test. The repuncture-associated factors were assessed using logistic regression analysis.

Results: There were no major or minor complications in either group. The rate of repuncture was significantly lower in the group using the newly developed puncture needle compared with the group using the routinely used puncture needle (p=0.01). The duration of the procedure was significantly shorter with the newly developed puncture needle compared with the routinely used puncture needle (p=0.01). In univariate analysis, the thickness of the abdominal wall (p=0.04) and the use of the newly developed puncture needle (p=0.01) were significantly associated with the rate of repuncture. In multivariate analysis, only the use of the newly developed puncture needle was significantly associated with the rate of repuncture.

Conclusion: Using this novel puncture needle with a hard plastic sheath and plastic wings, the rate of repuncture and the duration of the procedure were decreased without complications of US-guided paracentesis.
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http://dx.doi.org/10.12701/yujm.2021.01109DOI Listing
July 2021

Cytoplasmic expression of a model antigen with M Cell-Targeting moiety in lactic acid bacteria and implication of the mechanism as a mucosal vaccine via oral route.

Vaccine 2021 07 12;39(30):4072-4081. Epub 2021 Jun 12.

Graduate School of International Agricultural Technology, Seoul National University, Pyeongchang-gun 25354, Republic of Korea; Institute of Green-Bio Science & Technology, Seoul National University, Pyeongchang-gun 25354, Republic of Korea; Research Institute of Agriculture and Life Science, Seoul National University, Seoul 08826, Republic of Korea. Electronic address:

Lactic acid bacteria (LAB) have been widely studied as mucosal vaccine delivery carriers against many infectious diseases for heterologous expression of protein antigens. There are three antigen expression strategies for LAB: cytoplasmic expression (CE), cell surface display (SD), and extracellular secretion (ES). Despite the generally higher protein expression level and many observations of antigen-specific immunogenicity in CE, its application as a mucosal vaccine has been overlooked relative to SD and ES because of the antigens enclosed by the LAB cell wall. We hypothesized that the antigens in CE could be released from the LAB into the intestinal lumen before host bacterial access to gut-associated lymphoid tissue (GALT), which could contribute to antigen-specific immune responses after oral administration. To elucidate this hypothesis, three recombinant Lactobacillus plantarum (LP) strains were constructed to produce a model antigen, BmpB, with or without an M cell-targeting moiety, and their immunogenicities were analyzed comparatively as oral vaccines in mouse model. The data indicated that the recombinant LPs producing BmpBs with different conformations could induce mucosal immunity differentially. This suggests that the cytoplasmic antigens in LAB could be released into the intestinal lumen, subsequently translocated through M cells, and stimulate the GALT to generate antigen-specific immune responses. Therefore, the CE strategy has great potential, especially in the application of oral LAB vaccines as well as SD and ES strategies. This research provides a better understanding of the mechanism for recombinant oral LAB vaccines and gives insight to the future design of LAB vaccines and oral delivery applications for useful therapeutic proteins.
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http://dx.doi.org/10.1016/j.vaccine.2021.06.010DOI Listing
July 2021

MRI Features for Predicting Microvascular Invasion of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

Liver Cancer 2021 Apr 11;10(2):94-106. Epub 2021 Mar 11.

Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Republic of Korea.

Purpose: Microvascular invasion (MVI) is an important prognostic factor in patients with hepatocellular carcinoma (HCC). However, the reported results of magnetic resonance imaging (MRI) features for predicting MVI of HCC are variable and conflicting. Therefore, this meta-analysis aimed to identify the significant MRI features for MVI of HCC and to determine their diagnostic value.

Methods: Original studies reporting the diagnostic performance of MRI for predicting MVI of HCC were identified in MEDLINE and EMBASE up until January 15, 2020. Study quality was assessed using QUADAS-2. A bivariate random-effects model was used to calculate the meta-analytic pooled diagnostic odds ratio (DOR) and 95% confidence interval (CI) for each MRI feature for diagnosing MVI in HCC. The meta-analytic pooled sensitivity and specificity were calculated for the significant MRI features.

Results: Among 235 screened articles, we found 36 studies including 4,274 HCCs. Of the 15 available MRI features, 7 were significantly associated with MVI: larger tumor size (>5 cm) (DOR = 5.2, 95% CI [3.0-9.0]), rim arterial enhancement (4.2, 95% CI [1.7-10.6]), arterial peritumoral enhancement (4.4, 95% CI [2.8-6.9]), peritumoral hypointensity on hepatobiliary phase imaging (HBP) (8.2, 95% CI [4.4-15.2]), nonsmooth tumor margin (3.2, 95% CI [2.2-4.4]), multifocality (7.1, 95% CI [2.6-19.5]), and hypointensity on T1-weighted imaging (T1WI) (4.9, 95% CI [2.5-9.6]). Both peritumoral hypointensity on HBP and multifocality showed very high meta-analytic pooled specificities for diagnosing MVI (91.1% [85.4-94.8%] and 93.3% [74.5-98.5%], respectively).

Conclusions: Seven MRI features including larger tumor size, rim arterial enhancement, arterial peritumoral enhancement, peritumoral hypointensity on HBP, nonsmooth margin, multifocality, and hypointensity on T1WI were significant predictors for MVI of HCC. These MRI features predictive of MVI can be useful in the management of HCC.
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http://dx.doi.org/10.1159/000513704DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077694PMC
April 2021

The Measurement of Information and Free Energy in Mechanical-Force-Driven Coil-Globule Transitions.

J Phys Chem B 2021 May 11;125(19):4987-4997. Epub 2021 May 11.

Department of Physics, The Catholic University of Korea, Bucheon, Korea.

We study the role of information (the relative entropy) for polymers undergoing coil-globule transitions driven by a time-dependent force. Pulling experiments at various speeds are performed by Brownian dynamics simulations. We obtain the work distributions for the forward and time-reversed backward processes and information stored at the end of the nonequilibrium pulling processes. We present the systematic method to measure the information from the pulling experiments and extract the information by analyzing slowly relaxing modes. When the information is incorporated, the work distributions modified by the information allow access to the proper free energy via the formulation of the generalized fluctuation theorems even if the initial states of the forward and time-reversed backward processes are out of equilibrium. This demonstrates that the work-information conversion works well for a single-molecule system with many degrees of freedom.
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http://dx.doi.org/10.1021/acs.jpcb.1c01119DOI Listing
May 2021

Validation of functional liver imaging scores (FLIS) derived from gadoxetic acid-enhanced MRI in patients with chronic liver disease and liver cirrhosis: the relationship between Child-Pugh score and FLIS.

Eur Radiol 2021 Apr 21. Epub 2021 Apr 21.

Department of Radiology, Biomedical Research Institute, Pusan National University Yangsan Hospital, Pusan National University School of Medicine, Yangsan, South Korea.

Objectives: To validate the functional liver imaging score (FLIS) for prediction of hepatic function in gadoxetic acid-enhanced MRI.

Methods: We retrospectively identified 134 patients (88 men, 46 women; mean age, 58.8 years) between January 2015 and December 2018 with the following inclusion criteria: patients diagnosed with liver cirrhosis or chronic liver disease (CLD) who underwent gadoxetic acid-enhanced MRI. Three parameters on hepatobiliary phase images were evaluated for FLIS: liver parenchymal enhancement, biliary excretion, and signal intensity of the portal vein. Patients were classified as CLD (n = 11), Child-Pugh (CP) class A (n = 87), CP B (n = 22), or CP C (n = 14). We assessed the correlation between CP score and both FLIS and its components using Spearman rank correlation. Receiver operating characteristic (ROC) curve analysis was performed to demonstrate the cutoff value of FLIS for differentiating between CP classes. The associations between patient characteristics, serum markers, FLIS, and hepatic decompensation were evaluated with Cox proportional hazard models.

Results: FLIS and three FLIS parameters showed strong to very strong correlation with CP score (r = -0.60 to 0.82). ROC curve analysis showed that FLIS ≥ 5 was the optimal cutoff for prediction of CP class A or CLD (sensitivity, 83.7%; specificity, 94.4%; area under the curve [AUC], 0.93). FLIS < 5 was independently associated with the development of first hepatic decompensation in patients with CP A (HR, 50.0; 95% confidence interval, 6.2, 400.4).

Conclusion: FLIS showed a strong correlation with hepatic function and can stratify the CP class. In addition, FLIS can help prediction for the development of first decompensation.

Key Points: • Functional liver imaging scores (FLIS) and its three parameters, derived from hepatobiliary phase image, have strong to very strong correlations with Child-Pugh (CP) scores. • FLIS can stratify patients with chronic liver disease or liver cirrhosis according to CP classification. • Low FLIS is an independent predictor for first hepatic decompensation in patients with CP class A.
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http://dx.doi.org/10.1007/s00330-021-07955-1DOI Listing
April 2021

Multilocular cystic hemangioma of the liver mimicking mucinous cystic neoplasm.

Yeungnam Univ J Med 2021 Apr 7. Epub 2021 Apr 7.

Department of Surgery, Biomedical Research Institute and Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea.

Hepatic hemangiomas infrequently exhibit atypical imaging features, which may cause diagnostic confusion with hepatic malignancies and lead to unnecessary surgery. We report a rare case of multilocular cystic hemangioma of the liver mimicking a mucinous cystic neoplasm of the liver in a 48-year-old female, focusing on computed tomography and magnetic resonance imaging features and their differential diagnosis.
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http://dx.doi.org/10.12701/yujm.2021.00969DOI Listing
April 2021

Sequence-dependent cost for Z-form shapes the torsion-driven B-Z transition via close interplay of Z-DNA and DNA bubble.

Nucleic Acids Res 2021 04;49(7):3651-3660

Center for Molecular Spectroscopy and Dynamics, Institute for Basic Science, Seoul 02841 Korea.

Despite recent genome-wide investigations of functional DNA elements, the mechanistic details about their actions remain elusive. One intriguing possibility is that DNA sequences with special patterns play biological roles, adopting non-B-DNA conformations. Here we investigated dynamics of thymine-guanine (TG) repeats, microsatellite sequences and recurrently found in promoters, as well as cytosine-guanine (CG) repeats, best-known Z-DNA forming sequence, in the aspect of Z-DNA formation. We measured the energy barriers of the B-Z transition with those repeats and discovered the sequence-dependent penalty for Z-DNA generates distinctive thermodynamic and kinetic features in the torque-induced transition. Due to the higher torsional stress required for Z-form in TG repeats, a bubble could be induced more easily, suppressing Z-DNA induction, but facilitate the B-Z interconversion kinetically at the transition midpoint. Thus, the Z-form by TG repeats has advantages as a torsion buffer and bubble selector while the Z-form by CG repeats likely behaves as torsion absorber. Our statistical physics model supports quantitatively the populations of Z-DNA and reveals the pivotal roles of bubbles in state dynamics. All taken together, a quantitative picture for the transition was deduced within the close interplay among bubbles, plectonemes and Z-DNA.
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http://dx.doi.org/10.1093/nar/gkab153DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8053131PMC
April 2021

Structured reporting of CT or MRI for perihilar cholangiocarcinoma: usefulness for clinical planning and interdisciplinary communication.

Jpn J Radiol 2021 Apr 11;39(4):349-356. Epub 2020 Nov 11.

Department of Radiology, Biomedical Research Institute, Pusan National University Yansan Hospital, and Pusan National University school of Medicine, Yangsan, Korea.

Purpose: To compare the content and communication between the radiologist and the clinicians for treatment planning of structured reports (SRs) and narrative reports (NRs) for reporting CT/MRI findings in patients with perihilar cholangiocarcinoma.

Materials And Method: This retrospective study included 54 patients with perihilar cholangiocarcinoma who underwent CT/MRI before ERCP or surgery. For all patients, we generated both NRs and SRs for perihilar cholangiocarcinoma and compared the number of key features between NRs and SRs. In addition, three clinicians performed a questionnaire evaluation that included three questions regarding assessment of the sufficiency of information for surgical or procedural planning, the effort required for information extraction, and the report quality rated on a Likert scale.

Results: SRs included significantly more predefined key features (6.89 ± 0.31) than NRs (5.87 ± 0.70) (p < 0.001). SRs provided greater sufficiency of information for clinical planning than NRs (89.9% vs. 18.5% of the cases, respectively; p < 0.001). Extraction of information was easier from SRs than NRs (94.4% vs. 9.3%, respectively) (p < 0.001). SRs received a higher overall report quality rating (5.96 ± 0.19) than NRs (4.31 ± 0.77) (p < 0.001).

Conclusions: SRs of CT/MRI findings for hilar cholangiocarcinoma can reveal more predefined key features, provide more sufficiency of information, and yield higher satisfaction levels, in comparison with NRs.
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http://dx.doi.org/10.1007/s11604-020-01068-3DOI Listing
April 2021

Non-teratomatous ossification of the ovary, a rare entity: case report and review of the literature.

Int J Clin Exp Pathol 2020 1;13(9):2356-2362. Epub 2020 Sep 1.

Department of Pathology, Pusan National University School of Medicine Republic of Korea.

Ossification in non-teratomatous ovaries is extremely rare. This phenomenon may occur in various non-neoplastic or neoplastic ovarian diseases. A 34-year-old woman presented with lower abdominal pain of about 3 months. Transvaginal ultrasonography and plain abdominal radiography revealed an ovoid, calcified mass in left adnexa. Computed tomography (CT) demonstrated a well-defined cystic lesion measuring 7.7 × 5.1 cm with internal hemorrhage and peripheral curvilinear calcifications. The patient underwent laparoscopic surgery. The cut surface revealed a hemorrhagic cyst with a hardened wall and a muddy, yellow surface. Histologic examination revealed an ovarian hemorrhagic cyst with ossification. The authors present an unusual case of ossification in the ovary associated with an old hemorrhagic cyst and include a review of the literature.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7539864PMC
September 2020

First-line chemotherapy in very elderly patients with metastatic pancreatic cancer: Gemcitabine monotherapy combination chemotherapy.

World J Clin Cases 2020 Sep;8(18):4022-4033

Department of Surgery, Biomedical Research Institute, Pusan National University Hospital, Busan 49241, South Korea.

Background: Combination chemotherapy (gemcitabine plus nab-paclitaxel and FOLFIRINOX) is widely used as the standard first-line treatment for pancreatic cancer. Considering the severe toxicities of combination chemotherapy, gemcitabine monotherapy (G mono) could be used as a first-line treatment in very elderly patients or those with a low Eastern Cooperative Oncology Group status. However, reports on the efficacy of G mono in patients older than 75 years are limited.

Aim: To evaluate the efficacy of G mono and combination chemotherapy by comparing their clinical outcomes in very elderly patients with pancreatic cancer.

Methods: We retrospectively analyzed 104 older patients with pancreatic cancer who underwent chemotherapy with G mono ( = 45) or combination therapy ( = 59) as a first-line treatment between 2011 and 2019. All patients were histologically diagnosed with ductal adenocarcinoma. Primary outcomes were progression-free survival and overall survival. We also analyzed subgroups according to age [65-74 years (elderly) and ≥ 75 years (very elderly)]. Propensity score matching was performed to compare the outcomes between the two chemotherapy groups.

Results: The baseline characteristics were significantly different between the two chemotherapy groups, especially regarding age, ratio of multiple metastases, tumor burden, and Eastern Cooperative Oncology Group performance status. After propensity score matching, the baseline characteristics were not significantly different between the chemotherapy groups in elderly and very elderly patients. In the elderly patients, the median progression-free survival (62 d 206 d, = 0.000) and overall survival (102 d 302 d, = 0.000) were longer in the combination chemotherapy group. However, in the very elderly patients, the median progression-free survival (147 d and 174 d, respectively, = 0.796) and overall survival (227 d and 211 d, respectively, = 0.739) were comparable between the G mono and combination chemotherapy groups. Adverse events occurred more frequently in the combination chemotherapy group than in the G mono group, especially thromboembolism (G mono nab-paclitaxel FOLFIRINOX; 8.9% 5.9% 28%, = 0.041), neutropenia (40.0% 76.5% 84.0%, = 0.000), and neuropathy (0% 61.8% 28.0%, = 0.006).

Conclusion: In elderly patients, combination therapy is more effective than G mono. However, G mono is superior for the management of metastatic pancreatic cancer in very elderly patients.
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http://dx.doi.org/10.12998/wjcc.v8.i18.4022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520790PMC
September 2020

Free energy measurements by the generalized fluctuation theorems: Theory and numerical study of a model filament.

Eur Phys J E Soft Matter 2020 Sep 29;43(9):62. Epub 2020 Sep 29.

Department of Physics, The Catholic University of Korea, 14662, Bucheon, South Korea.

We measure the free energy of a model filament, which undergoes deformations and structural transitions, as a function of its extension, in silico. We perform Brownian Dynamics (BD) simulations of pulling experiments at various speeds, following a protocol close to experimental ones. The results from the fluctuation theorems are compared with the estimates from Monte Carlo (MC) simulation, where the rugged free energy landscape is produced by the density of states method. The fluctuation theorems (FT) give accurate estimates of the free energy up to moderate pulling speeds. At higher pulling speeds, the work distributions do not efficiently sample the domain of small work and FT slightly overestimates free energy. In order to comprehend the differences, we analyze the work distributions from the BD simulations in the framework of trajectory thermodynamics and propose the generalized fluctuation theorems that take into account the information (relative entropy) evaluated in the expanded phase space. The measured work - free energy relation is consistent with the results obtained from the generalized fluctuation theorems. We discuss operational methods to improve the estimates at high pulling speed.
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http://dx.doi.org/10.1140/epje/i2020-11984-5DOI Listing
September 2020

Comparison of gemcitabine plus nab-paclitaxel and FOLFIRINOX in metastatic pancreatic cancer.

World J Clin Cases 2020 Sep;8(17):3718-3729

Department of Surgery, Biomedical Research Institute, Pusan National University Hospital, Busan 49241, South Korea.

Background: Gemcitabine plus nab-paclitaxel (GA) and modified FOLFIRINOX (FFX) have been widely used as standard first-line treatment in pancreatic cancer. However, it is unclear which regimen is more efficacious.

Aim: To evaluate a retrospective analysis comparing the efficacy and safety of FFX and GA as first-line chemotherapeutic regimens in patients with metastatic pancreatic cancer.

Methods: We retrospectively analyzed and compared outcomes in 101 patients who presented with pancreatic cancer and were treated with either GA ( = 54) or FFX ( = 47). Moreover, we performed subgroup analysis based on the neutrophil/lymphocyte ratio (NLR) and Eastern Cooperative Oncology Group (ECOG) performance status.

Results: There were no significant differences between two groups in baseline characteristics, except for the ECOG performance status. The median progression-free survival (PFS) (6.43 mo 4.90 mo, = 0.058) was comparable between two groups; however, median overall survival (OS) (10.17 mo 6.93 mo, = 0.008) was longer in patients who received GA regimen. In patients with ECOG 0 (PFS: 8.93 mo 5.43 mo, = 0.002; OS: 16.10 mo 6.97 mo, = 0.000) and those with NLR < 3 (PFS: 8.10 mo 6.57 mo, = 0.008; OS: 12.87 mo 9.93 mo, = 0.002), GA regimen showed higher efficacy.

Conclusion: GA regimen may be recommended to the patients with NLR < 3 or ECOG 0 status although GA and FFX showed comparable efficacy outcomes in patients with metastatic pancreatic cancer.
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http://dx.doi.org/10.12998/wjcc.v8.i17.3718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7479547PMC
September 2020

ALPPL2 Is a Highly Specific and Targetable Tumor Cell Surface Antigen.

Cancer Res 2020 10 31;80(20):4552-4564. Epub 2020 Aug 31.

Department of Anesthesia, University of California, San Francisco, San Francisco, California.

Identification of tumor-specific cell surface antigens has proven challenging, as the vast majority of tumor-associated antigens are also expressed in normal tissues. In mesothelioma, we identified a highly specific tumor cell surface antigen that can be targeted for therapy development. Mesothelioma is caused by malignant transformation of the mesothelium, is incurable, and can be categorized into three histologic subtypes: epithelioid, biphasic, and sarcomatoid. To identity novel mesothelioma cell surface antigens with broad subtype coverage and high tissue specificity, we have previously selected phage antibody display libraries on live mesothelioma cells and tissues following counterselection on normal cells and identified a panel of human antibodies that bind all subtypes of mesothelioma, but not normal mesothelium. One of the antibodies, M25, showed high specificity against an antigen we identify here as ALPPL2. IHC on normal human tissues found that ALPPL2 is expressed only on placental trophoblasts, but not on any other normal tissues. This significant tissue specificity and broad tumor type coverage suggest that ALPPL2 could be an excellent cell surface target for therapeutic development against mesothelioma. To evaluate therapeutic potential of ALPPL2 targeting, an ALPPL2-targeted antibody-drug conjugate was developed and demonstrated potent and specific tumor killing and against both epithelioid and sarcomatoid mesothelioma. Thus, ALPPL2 belongs to a rare class of cell surface antigens classified as truly tumor specific and is well suited for therapy development against ALPPL2-expressing tumors. SIGNIFICANCE: These findings identify ALPP2 as a true tumor-specific cell surface antigen whose tissue specificity enables the development of novel therapies.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-1418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572689PMC
October 2020

Vesical Imaging-Reporting and Data System for Multiparametric MRI to Predict the Presence of Muscle Invasion for Bladder Cancer.

J Magn Reson Imaging 2020 10 27;52(4):1249-1256. Epub 2020 Mar 27.

Department of Pathology, Biomedical Research Institute, Pusan National University Hospital, and Pusan National University School of Medicine, Busan, Korea.

Background: The Vesical Imaging-Reporting and Data System (VI-RADS) is a newly developed system of bladder cancer staging with multiparametric MRI (mpMRI), which can be used to predict the presence of muscle invasion for bladder cancer.

Purpose: To evaluate the accuracy of three mpMRI series (T WI, diffusion-weighted imaging [DWI], and dynamic contrast-enhanced image [DCEI]) and VI-RADS for diagnosing the muscle invasive bladder cancer (MIBC).

Study Type: Retrospective.

Population: In all, 66 pathologically proven bladder cancers in 32 patients.

Field Strength/sequence: Before the diagnostic MRI with an intramuscular antispasmodic agent, optimal bladder distension was confirmed. 3.0T MRI with T WI, DWI, and DCEI.

Assessment: Three reviewers independently assessed and scored the bladder cancers in T WI, DWI, and DCEI using a five-point score system. Based on the scores in the three sequences, reviewers scored each bladder cancer with reference to VI-RADS categories. We evaluated the diagnostic performance of each of three mpMRI sequences and the final VI-RADS categorization for diagnosing MIBC.

Statistical Tests: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the curve (AUC) of each of three sequences separately and VI-RADS categorization for diagnosing the MIBC.

Results: The diagnostic performances of each of the three mpMRI series and VI-RADS for diagnosing MIBC were excellent. Especially using the optimal cutoff score >3 for predicting MIBC on DWI, DCEI, and VI-RADS, the sensitivity, specificity, PPV, NPV, and AUC values were 90% (95% confidence interval [CI]: 0.56, 1.00), 100% (95% CI: 0.94, 1.00), 100% (95% CI: 0.66. 1.00), 98.3% (95% CI: 0.91, 1.00), and 0.95, respectively. DATA CONCLUSION: mpMRI based on VI-RADS can stratify patients with bladder cancer according to the presence of muscle invasion.

Level Of Evidence: 3.

Technical Efficacy Stage: 2. J. Magn. Reson. Imaging 2020;52:1249-1256.
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http://dx.doi.org/10.1002/jmri.27141DOI Listing
October 2020

Coexistence of adenoid cystic carcinoma and squamous cell carcinoma of the uterine cervix with HPV 16 infection: clinical course of delayed adjuvant treatment.

Int J Clin Exp Pathol 2019 1;12(4):1418-1423. Epub 2019 Apr 1.

Biomedical Research Institute, Pusan National University Hospital Busan, Republic of Korea.

Adenoid cystic carcinoma (ACC) is a rare variant of cervical carcinoma and has an aggressive clinical behavior, and there have been few reports of co-existing ACC and squamous cell carcinoma (SCC) of the uterine cervix. A 76-year-old postmenopausal woman presented with vaginal bleeding. The cervical cytology and polypectomy results were SCC, and magnetic resonance imaging (MRI) of pelvis revealed a 2.3 × 1.8 cm sized lobulated mass at the cervix. Microscopically, the tumor showed infiltrative nests of squamoid cells and a cribriform pattern of basaloid cells. Immunohistochemical studies showed that squamous cells were positive for p63 and that basaloid cells were mainly positive for CD117 and S-100 protein. Both components were strongly positive for p16 immunostaining. The tumor was diagnosed as invasive SCC with concurrent ACC. The disease relapsed after a follow-up of 14 months with no adjuvant therapy. Subsequently, she received concurrent chemoradiotherapy (CCRT) and then combined chemotherapy with paclitaxel, cisplatin, and bevacizumab; finally, imaging revealed no evidence of residual cancer.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947050PMC
April 2019

Large cell neuroendocrine carcinoma arising from uterine endometrium with rapidly progressive course: report of a case and review of literature.

Int J Clin Exp Pathol 2019 1;12(4):1412-1417. Epub 2019 Apr 1.

Department of Obstetrics and Gynecology, Pusan National University School of Medicine Busan, Republic of Korea.

Large cell neuroendocrine carcinoma (LCNEC) of the endometrium is a rare and highly malignant neoplasm with no characteristic findings in terms of clinical manifestations, diagnostic imaging, or pathology, and thus, the definitive preoperative diagnosis of LCNEC is difficult. A 61-year-old postmenopausal woman presented with low abdominal pain and a rapidly growing uterine mass without postmenopausal bleeding. Magnetic resonance imaging of the pelvis revealed an enlarged uterus with a 7.5 cm mass. Intraoperative frozen examination revealed a malignant tumor, and accordingly, cytoreductive surgery was performed. Microscopically, the tumor showed extensive necrosis, hemorrhage, and an organoid nesting pattern of large cells. Immunohistochemistry revealed tumor cells were diffusely positive for the neuroendocrine markers CD56 and synaptophysin. Thus the tumor was diagnosed as LCNEC of endometrium. Postoperatively, the disease pursued a progressive course and relapsed even after repeated multiple chemotherapy courses. The patient succumbed to the disease 23 months after surgery. We present a case of LCNEC of the endometrium with a high Ki-67 index that exhibited a rapidly progressive course. LCNEC should be considered when a rapidly growing uterine tumor is detected.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6947078PMC
April 2019

An unusual case of dedifferentiated leiomyosarcoma of the primary mesentery mimicking ovarian cancer.

Int J Clin Exp Pathol 2019 1;12(11):4150-4155. Epub 2019 Nov 1.

Department of General Surgery, Pusan National University School of Medicine Busan, Republic of Korea.

Dedifferentiated leiomyosarcoma of the primary mesentery is extremely rare. We report a case of dedifferentiated leiomyosarcoma (LMS) of the primary mesentery mimicking ovarian cancer. A 62-year-old woman presented with progressive low abdominal pain. Pelvic magnetic resonance imaging (MRI) revealed a large adnexal mass with carcinomatosis peritonei. Laboratory examination revealed an elevated serum level WBC 46,520/uL (Ref. 4,000~11,000/uL), PLT 687,000/uL (Ref. 140,000~400,000/uL), CA-125 69.1 U/mL (Ref. 0~35 U/mL), and beta-hCG 43.1 mIU/mL (Ref. 0~5 mIU/mL) level. The patient underwent exploratory laparotomy under suspicion of ovarian cancer. We observed a 20-25 cm-sized huge pedunculated subserosal mass arising from the mesentery, and other masses with sizes of 15-20 cm were adherent to peritoneum and ileocecal region. There was a multiple seeding metastasis in the omentum and bowel mesentery. A frozen section revealed malignancy originating from the mesentery, and thus, total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic and para-aortic lymph node dissection, and mass excision were performed. Subsequent histopathologic examination resulted in a final diagnosis of dedifferentiated leiomyosarcoma of the mesentery. The patient was transferred to a department of hemato-oncologist for additional managements. Doxorubicin was used for adjuvant chemotherapy.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6949801PMC
November 2019

CT diagnosis of non-traumatic gastrointestinal perforation: an emphasis on the causes.

Jpn J Radiol 2020 Feb 17;38(2):101-111. Epub 2019 Dec 17.

Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, and Pusan National University School of Medicine, 179, Gudeok-ro, Seo-gu, Busan, 49241, Korea.

Gastrointestinal tract (GI) perforations can occur due to various causes such as trauma, iatrogenic factor, infectious condition, peptic ulcer, inflammatory disease, or a neoplasm. Because GI perforations represent an emergency and life-threatening condition, prompt diagnosis and surgical treatment are required in most cases. However, according to the underlying causes of GI perforations, additional treatment strategies may be needed. Adjuvant chemotherapy or immunotherapy may be required in various GI neoplasms such as adenocarcinoma, lymphoma or gastrointestinal stromal tumor. Inflammatory bowel disease is a chronic disease repeating cycle of intermittent, thus appropriate medical treatment and periodic follow-up are also required. Moreover, vascular intervention may have a role in some cases of mesenteric ischemia associated with mesenteric artery occlusion. Recently, computed tomography (CT) has been the first choice for patients with suspected GI perforations, because CT plays an important role in the accurate assessment of the perforation site, the pathology causing the perforation and the ensuing complications. This review will illustrate characteristic CT findings that differentiate underlying pathologies causing GI perforations to help clinicians decision-making regarding an optimal treatment plan.
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http://dx.doi.org/10.1007/s11604-019-00910-7DOI Listing
February 2020

Meta-analysis of MRI for the diagnosis of liver metastasis in patients with pancreatic adenocarcinoma.

J Magn Reson Imaging 2020 06 30;51(6):1737-1744. Epub 2019 Oct 30.

Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, Korea.

Background: Determining if a given patient with primary pancreatic adenocarcinoma (PDA) has hepatic metastasis is important for treatment planning. Several previous studies reported on the diagnostic performance of MRI for liver metastasis in patients with PDA. But the reported data are quite variable.

Purpose: To systematically determine the diagnostic performance of MRI for liver metastasis in patients with PDA, including comparing it with computed tomography (CT).

Study Type: Systemic review and meta-analysis.

Subjects: In all, 457 patients from five eligible articles.

Field Strength/sequence: Conventional MR sequences with or without contrast enhancement at 1.5T and 3T.

Assessment: Two reviewers independently performed the data extraction. The reviewers identified and reviewed the original articles reporting the diagnostic performance of MRI for liver metastases in patients with PDA, including those articles making comparisons with CT.

Statistical Tests: Meta-analytic summary sensitivity and specificity were calculated on a per-patient basis using a bivariate random effects model. We compared the meta-analytic summary sensitivity and specificity between MRI and CT.

Results: The meta-analytic summary sensitivity and specificity were 85% (95% confidence interval [CI], 74-92%; I = 0%) and 98% (95% CI, 78-100%; I = 85%), respectively. In comparison with CT, MRI showed a higher sensitivity (85% vs. 75%) but similar specificity (98% vs. 94%).

Data Conclusion: MRI had good overall diagnostic performance for liver metastasis in patients with PDA, with a higher sensitivity than CT.

Level Of Evidence: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:1737-1744.
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http://dx.doi.org/10.1002/jmri.26969DOI Listing
June 2020

Diffusion-weighted MRI of estrogen receptor-positive, HER2-negative, node-negative breast cancer: association between intratumoral heterogeneity and recurrence risk.

Eur Radiol 2020 Jan 5;30(1):66-76. Epub 2019 Aug 5.

Siemens Healthcare GmbH, Erlangen, Germany.

Objectives: To investigate possible associations between quantitative apparent diffusion coefficient (ADC) metrics derived from whole-lesion histogram analysis and breast cancer recurrence risk in women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-negative breast cancer who underwent the Oncotype DX assay.

Methods: This retrospective study was conducted on 105 women (median age, 48 years) with ER-positive, HER2-negative, node-negative breast cancer who underwent the Oncotype DX test and preoperative diffusion-weighted imaging (DWI). Histogram analysis of pixel-based ADC data of whole tumors was performed, and various ADC histogram parameters (mean, 5th, 25th, 50th, 75th, and 95th percentiles of ADCs) were extracted. The ADC difference value (defined as the difference between the 5th and 95th percentiles of ADCs) was calculated to assess intratumoral heterogeneity. Associations between quantitative ADC metrics and the recurrence risk, stratified using the Oncotype DX recurrence score (RS), were evaluated.

Results: Whole-lesion histogram analysis showed that the ADC difference value was different between the low-risk recurrence (RS < 18) and the non-low-risk recurrence (RS ≥ 18; intermediate to high risk of recurrence) groups (0.600 × 10 mm/s vs. 0.746 × 10 mm/s, p < 0.001). Multivariate regression analysis demonstrated that a lower ADC difference value (< 0.559 × 10 mm/s; odds ratio [OR] = 5.998; p = 0.007) and a small tumor size (≤ 2 cm; OR = 3.866; p = 0.012) were associated with a low risk of recurrence after adjusting for clinicopathological factors.

Conclusions: The ADC difference value derived from whole-lesion histogram analysis might serve as a quantitative DWI biomarker of the recurrence risk in women with ER-positive, HER2-negative, node-negative invasive breast cancer.

Key Points: • A lower ADC difference value and a small tumor size were associated with a low risk of recurrence of breast cancer. • The ADC difference value could be a quantitative marker for intratumoral heterogeneity. • Whole-lesion histogram analysis of the ADC could be helpful for discriminating the low-risk from non-low-risk recurrence groups.
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http://dx.doi.org/10.1007/s00330-019-06383-6DOI Listing
January 2020

Studies on the physicochemical characteristics of the New Zealand deer's tail, var. (III).

Food Sci Biotechnol 2019 Aug 2;28(4):1013-1025. Epub 2019 Mar 2.

Laboratory of Fundamental Research, R&D Headquarters, Korea Ginseng Corp., 30, Gajeong-ro, Yuseong-gu, Daejeon, 34128 Korea.

This study was designed to determine the nutritional profile and functional components of the NZT (New Zealand deer's tail, var Lönnberg). Twenty-nine fatty acids, eighteen amino acids, twenty-five minerals, chondroitin, and phospholipids were detected by the auto-fatty acid analyzer, auto-amino acid analyzer, inductively coupled plasma optical emission spectrophotometer, absorbance measurements, and by weighing after separating, respectively. 7-Ketocholesterol was isolated from alcohol extract by silica gel column chromatography analysis. Four steroid hormones (androstene-3,17-dione, β-estradiol, testosterone, and dehydroepiandrosterone), one base and seven nucleosides, and -acetylneuraminic acid were detected by a HPLC-photodiode array and HPLC-fluorescence detector. As a result, NZT was composed of many nutritional and functional ingredients found in New Zealand deer's antler (NZA) which was one of deer co-products, and it was considered that NZT could be a novel health food resource such as NZA.
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http://dx.doi.org/10.1007/s10068-019-00558-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6595039PMC
August 2019

Grand-canonical polymers under confinement: Dense solutions.

J Chem Phys 2019 May;150(17):174907

Institute Charles Sadron, CNRS, 23 Rue du Loess, 67034 Strasbourg Cedex 2, France.

We theoretically study dense polymer solutions under open (capillary and slit) and closed (box) confinement. The theory is formulated for grand-canonical polymers and corrections to the self-consistent mean-field results are discussed. In contrast to the mean-field prediction, we found that the partition function of a labeled chain is affected by confinement even under neutral von Neumann boundary conditions and the chain length distribution is biased to short chains. As the container size increases, the contribution of the transverse excited states to the free energy of a labeled chain is found to approach its bulk value nonmonotonically (through an extremum) for the box and the capillary confinement but not for the slit. So does the confinement free energy of a labeled chain. The confinement energy of the solution is well behaved for open confinement but formally diverges for a closed box in the limit that the average chain length goes to infinity. Counted per chain, the confinement energy of the dense solution is qualitatively weaker than for a single ideal chain under similarly strong confinement (by one power in transverse container size). The container boundary contributes a surface tension to the free energy, which makes the effective monomer-wall affinity more repulsive. This correction increases with the average chain length. If present, edge or vertex singularities also contribute to the grand potential of the solution.
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http://dx.doi.org/10.1063/1.5094879DOI Listing
May 2019

Polymers grown in cavities: Vesicles and droplets.

J Chem Phys 2019 Apr;150(16):164905

Institute Charles Sadron, CNRS, 23 Rue du Loess, 67034 Strasbourg Cedex 2, France.

In synthetic chemistry and biological or biomimetic systems, polymers are often grown in cavities. Polymerizations in microemulsions, biopolymers grown in cells, or in vesicles containing artificial organelles have an influence on the shape of liquid boundaries. We consider confined grand-canonical polymers to address equilibrium properties of annealed polymers. We calculate the concentration profiles established by annealed (star-) polymers inside a confining cavity. Our emphasis is on the description of pressure fields derived from the contact theorem. We further show how the pressure field exerted by a localized annealed polymer (or pair of polymers) deforms the confining vesicle/ microemulsions droplet.
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http://dx.doi.org/10.1063/1.5064450DOI Listing
April 2019

Low-Dose CT With the Adaptive Statistical Iterative Reconstruction V Technique in Abdominal Organ Injury: Comparison With Routine-Dose CT With Filtered Back Projection.

AJR Am J Roentgenol 2019 09 30;213(3):659-666. Epub 2019 Apr 30.

Department of Radiology, Biomedical Research Institute, Pusan National University Hospital, Pusan National University School of Medicine, 305 Gudeok-Ro, Seo-Gu, Busan 49241, Korea.

The purpose of this study was to evaluate and compare the diagnostic performance and image quality of low-dose CT performed with adaptive statistical iterative reconstruction (ASIR)-V with those of routine-dose CT with filtered back projection (FBP) in the evaluation of abdominal organ injury. The study enrolled 197 patients with trauma who underwent multiphase abdominal CT, including routine-dose portal venous phase imaging with FBP and low-dose delayed phase imaging with 50% ASIR-V. The presence of abdominal organ injuries (liver, spleen, pancreas, kidney) was reviewed, and injuries were graded according to American Association for the Surgery of Trauma (AAST) scales. CT detection rates of organ injury and AAST grading with the two protocols were compared by McNemar test. Subjective analysis of image noise and artifacts and objective analysis of CT noise were performed by unpaired test. Compared with the routine-dose protocol, the low-dose protocol enabled an mean dose reduction of 59.8%. The detection rates and diagnostic performance of AAST grading did not differ significantly between the two protocols (detection rate, = 0.289; diagnostic performance, > 0.999). Objective image noise was significantly less with the low-dose protocol than with the routine-dose protocol ( < 0.001). Subjective imaging artifacts were similar between the low-dose and routine-dose protocols ( = 0.539). Compared with routine-dose protocol with FBP, low-dose CT with ASIR-V was useful for assessing multiorgan abdominal injury without impairing image quality.
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http://dx.doi.org/10.2214/AJR.18.20827DOI Listing
September 2019

Modified CAIPIRINHA-VIBE without view-sharing on gadoxetic acid-enhanced multi-arterial phase MR imaging for diagnosing hepatocellular carcinoma: comparison with the CAIPIRINHA-Dixon-TWIST-VIBE.

Eur Radiol 2019 Jul 16;29(7):3574-3583. Epub 2019 Apr 16.

Department of Radiology, Biomedical Research Institute, Pusan National University Yangsan Hospital, and Pusan National University School of Medicine, Busan, South Korea.

Purpose: We evaluated the detection rate and degree of motion artifact of the modified CAIPIRINHA-VIBE (mC-VIBE) without view-sharing and compare them with the CAIPIRINHA-Dixon-TWIST-VIBE (CDT-VIBE) with view-sharing on multi-arterial gadoxetic acid-enhanced liver MRI in the assessment of hepatocellular carcinoma (HCC).

Material And Methods: We retrospectively identified 114 pathological-proven hepatic tumors in 114 patients with risk of HCC who underwent multi-arterial gadoxetic acid-enhanced MRI between June 2016 and June 2018. All patients underwent triple arterial phase imaging using the mC-VIBE without view-sharing (54 patients; 49 HCCs and 5 non-HCCs) or the CDT-VIBE with view-sharing (60 patients; 55 HCCs and 5 non-HCCs). We compared the detection rate of two sequences for HCC, with reference to LI-RADS.V.2017. We also compared the mean motion scores and proportions of transient severe motion (TSM) in two sequences.

Result: For the examination using the mC-VIBE, the HCC-detection rate was significantly higher, compared with that using CDT-VIBE (93.9% [46/49] vs 80.0% [44/55], respectively; p = 0.047). For the examination with the mC-VIBE, mean motion scores were significantly lower compared with those of CDT-VIBE for all multi-arterial phases (1.21, 1.19, and 1.15 vs. 1.82, 1.85, and 1.84, respectively; p < 0.001 for all three comparisons). The proportion of TSM in the CDT-VIBE was significantly higher than that in the mC-VIBE (15.0% [9/60] vs 0.0% [0/54], respectively; p = 0.003).

Conclusion: In multi-arterial phase gadoxetic acid-enhanced MRI, the mC-VIBE sequence without view-sharing has slightly higher HCC-detection rate and fewer motion artifacts compared with CDT-VIBE with view-sharing.

Key Points: • Multi-arterial phase using the mC-VIBE without view-sharing can overcome motion artifacts, resulting in providing optimal arterial phase imaging. • The HCC-detection rate is slightly higher with the mC-VIBE vs. CAIPIRINHA-Dixon-TWIST-VIBE with view-sharing (CDT-VIBE). • View-sharing of CDT-VIBE in the multi-arterial phase is associated with increased frequency of TSM.
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http://dx.doi.org/10.1007/s00330-019-06095-xDOI Listing
July 2019

Manipulation of Cell-Type Selective Antibody Internalization by a Guide-Effector Bispecific Design.

Mol Cancer Ther 2019 06 8;18(6):1092-1103. Epub 2019 Apr 8.

Department of Anesthesia, UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California.

Cell-type-specific intracellular payload delivery is desired for antibody-based-targeted therapy development. However, tumor-specific internalizing antigens are rare to find, and even rarer for those that are expressed at uniformly high levels. We constructed a bispecific antibody that is composed of a rapidly internalizing antibody binding to a tumor-associated antigen, ephrin receptor A2 (EphA2), and a noninternalizing antibody binding to a highly expressed tumor-associated antigen, activated leukocyte cell adhesion molecule (ALCAM). We found that the overall internalization property of the bispecific is profoundly impacted by the relative surface expression level (antigen density ratio) of EphA2 versus ALCAM. When the EphA2-to-ALCAM ratio is greater than a threshold level (1:5), the amount of the bispecific taken into the tumor cell exceeds what is achieved by either the monoclonal internalizing antibody or a mixture of the two antibodies, showing a bispecific-dependent amplification effect where a small amount of the internalizing antigen EphA2 induces internalization of a larger amount of the noninternalizing antigen ALCAM. When the ratio is below the threshold, EphA2 can be rendered noninternalizing by the presence of excess ALCAM on the same cell surface. We constructed a bispecific antibody-drug conjugate (ADC) based on the above bispecific design and found that the bispecific ADC is more potent than monospecific ADCs in tumor cell killing both and Thus, the internalizing property of a cell surface antigen can be manipulated in either direction by a neighboring antigen, and this phenomenon can be exploited for therapeutic targeting.
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http://dx.doi.org/10.1158/1535-7163.MCT-18-1313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6548581PMC
June 2019

Influence of Heart Rate and Innovative Motion-Correction Algorithm on Coronary Artery Image Quality and Measurement Accuracy Using 256-Detector Row Computed Tomography Scanner: Phantom Study.

Korean J Radiol 2019 01 27;20(1):94-101. Epub 2018 Dec 27.

Department of Radiology, Pusan National University School of Medicine and Medical Research Institute, Pusan National University Hospital, Busan, Korea.

Objective: To investigate the efficacy of motion-correction algorithm (MCA) in improving coronary artery image quality and measurement accuracy using an anthropomorphic dynamic heart phantom and 256-detector row computed tomography (CT) scanner.

Materials And Methods: An anthropomorphic dynamic heart phantom was scanned under a static condition and under heart rate (HR) simulation of 50-120 beats per minute (bpm), and the obtained images were reconstructed using conventional algorithm (CA) and MCA. We compared the subjective image quality of coronary arteries using a four-point scale (1, excellent; 2, good; 3, fair; 4, poor) and measurement accuracy using measurement errors of the minimal luminal diameter (MLD) and minimal luminal area (MLA).

Results: Compared with CA, MCA significantly improved the subjective image quality at HRs of 110 bpm (1.3 ± 0.3 vs. 1.9 ± 0.8, = 0.003) and 120 bpm (1.7 ± 0.7 vs. 2.3 ± 0.6, = 0.006). The measurement error of MLD significantly decreased on using MCA at 110 bpm (11.7 ± 5.9% vs. 18.4 ± 9.4%, = 0.013) and 120 bpm (10.0 ± 7.3% vs. 25.0 ± 16.5%, = 0.013). The measurement error of the MLA was also reduced using MCA at 110 bpm (19.2 ± 28.1% vs. 26.4 ± 21.6%, = 0.028) and 120 bpm (17.9 ± 17.7% vs. 34.8 ± 19.6%, = 0.018).

Conclusion: Motion-correction algorithm can improve the coronary artery image quality and measurement accuracy at a high HR using an anthropomorphic dynamic heart phantom and 256-detector row CT scanner.
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http://dx.doi.org/10.3348/kjr.2018.0251DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6315068PMC
January 2019

Targeting CD46 for both adenocarcinoma and neuroendocrine prostate cancer.

JCI Insight 2018 09 6;3(17). Epub 2018 Sep 6.

Department of Anesthesia.

Although initially responsive to androgen signaling inhibitors (ASIs), metastatic castration-resistant prostate cancer (mCRPC) inevitably develops and is incurable. In addition to adenocarcinoma (adeno), neuroendocrine prostate cancer (NEPC) emerges to confer ASI resistance. We have previously combined laser capture microdissection and phage antibody display library selection on human cancer specimens and identified novel internalizing antibodies binding to tumor cells residing in their tissue microenvironment. We identified the target antigen for one of these antibodies as CD46, a multifunctional protein that is best known for negatively regulating the innate immune system. CD46 is overexpressed in primary tumor tissue and CRPC (localized and metastatic; adeno and NEPC), but expressed at low levels on normal tissues except for placental trophoblasts and prostate epithelium. Abiraterone- and enzalutamide-treated mCRPC cells upregulate cell surface CD46 expression. Genomic analysis showed that the CD46 gene is gained in 45% abiraterone-resistant mCRPC patients. We conjugated a tubulin inhibitor to our macropinocytosing anti-CD46 antibody and showed that the resulting antibody-drug conjugate (ADC) potently and selectively kills both adeno and NEPC cell lines in vitro (sub-nM EC50) but not normal cells. CD46 ADC regressed and eliminated an mCRPC cell line xenograft in vivo in both subcutaneous and intrafemoral models. Exploratory toxicology studies of the CD46 ADC in non-human primates demonstrated an acceptable safety profile. Thus, CD46 is an excellent target for antibody-based therapy development, which has potential to be applicable to both adenocarcinoma and neuroendocrine types of mCRPC that are resistant to current treatment.
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http://dx.doi.org/10.1172/jci.insight.121497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6171802PMC
September 2018
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