Comparison of Long-Term Efficacy in S-1 and Capecitabine With Oxaliplatin as Adjuvant Chemotherapy for Patients With Gastric Cancer After Curative Surgery: A Retrospective, Single-Center Observational Study.

Purpose: Various adjuvant chemotherapies have been introduced for gastric cancer patients after gastrectomy with D2 lymph node dissection. Although the mainstream regimen of adjuvant chemotherapy in Korea includes S-1 monotherapy (TS-1) and capecitabine with oxaliplatin (XELOX), few studies have compared the long-term efficacies of these 2 regimens. Methods: Between January 2010 and June 2017, 2021 patients were diagnosed with gastric cancer and underwent curative resection with adjuvant chemotherapy at our institution. Of 1461 patients with stage IB-III gastric cancer, 825 received TS-1 and 636 received XELOX as adjuvant chemotherapy. We retrospectively reviewed their medical records and analyzed the postoperative 5-year overall survival (OS) and disease-free survival (DFS) of these 2 groups. Results: The patients in the XELOX group had more advanced stage of cancer than the TS-1 group (stages III and II: 56.6% and 43.1%, respectively, in XELOX and 35.3% and 57.0% in TS-1; P < .001). The DFS did not differ significantly between the 2 study groups at any pathologic stage. The OS differed significantly only at pathologic stages IIA (P = .024) and IIB (P = .015). In a multivariate analysis of stage II patients, type of regimen was an independent prognostic factor of OS (XELOX vs TS-1; hazard ratio: 0.47, 95% confidence interval: 0.25-0.89, P = .021). Conclusion: There were similar long-term efficacies between these 2 regimens in advanced gastric cancer patients who underwent curative surgery. However, the XELOX regimen might be favorable for OS of stage II patients.

Sestrins induce natural killer function in senescent-like CD8+ T cells.

Aging is associated with remodeling of the immune system to enable the maintenance of life-long immunity. In the CD8+ T cell compartment, aging results in the expansion of highly differentiated cells that exhibit characteristics of cellular senescence. Here we found that CD27-CD28-CD8+ T cells lost the signaling activity of the T cell antigen receptor (TCR) and expressed a protein complex containing the agonistic natural killer (NK) receptor NKG2D and the NK adaptor molecule DAP12, which promoted cytotoxicity against cells that expressed NKG2D ligands. Immunoprecipitation and imaging cytometry indicated that the NKG2D-DAP12 complex was associated with sestrin 2. The genetic inhibition of sestrin 2 resulted in decreased expression of NKG2D and DAP12 and restored TCR signaling in senescent-like CD27-CD28-CD8+ T cells. Therefore, during aging, sestrins induce the reprogramming of non-proliferative senescent-like CD27-CD28-CD8+ T cells to acquire a broad-spectrum, innate-like killing activity.

Loss of ASXL1 expression is associated with lymph node metastasis in colorectal cancer.

CONTEXT: The function of ASXL1 in colorectal cancer (CRC) has not been investigated yet. AIMS: The purpose of this study was to investigate the clinicopathological and prognostic impact of ASXL1 expression on CRC. SETTINGS AND DESIGN: The intensity of expression was scored as 0-3, and the extent of staining was scored as 0-4, based on the percentage of positive cells. The immunoreactivity score (IRS) was calculated by multiplying the two scores. MATERIALS AND METHODS: We performed immunohistochemical staining of ASXL1 using tissue microarrays of 408 CRCs, 46 normal colonic mucosae, 48 adenomas, and 92 metastatic lymph nodes. STATISTICAL ANALYSIS USED: Clinicopathological variables were compared using Fisher's exact test, χ2-test, or unpaired Student's t-test, depending on the nature of the data. RESULTS: A negative expression of ASXL1 was observed in 10.9% of normal mucosae, 27.1% of adenomas, 55.6% of adenocarcinomas, and 71.7% of metastatic lymph nodes (P < 0.001). With respect to the IRS cut-off score, lymph node metastasis and lymphatic invasion were more frequent in the IRS 0-6 group than in the IRS 8-12 group (56.3% vs. 33.3%, P = 0.034; 56.0% vs. 33.3%, P = 0.035). The 5-year disease-free survival rate was significantly lower in patients with IRS 0-6 group than those with IRS 8-12 group (78.7 ± 2.5 vs. 100%, P = 0.034). CONCLUSION: ASXL1 might act as a tumor suppressor in CRC. The loss of ASXL1 expression might be associated with lymph node metastasis and lymphatic invasion in CRC.

Effects of Leucosporidium-derived ice-binding protein (LeIBP) on bull semen cryopreservation.

We examined the effect of ice-binding protein derived from Leucosporidium (LeIBP) on the cryopreservation of bull semen and compared it with that derived from previously reported Antifreeze Protein III (AFPIII). Six concentrations of LeIBP (10-1  ~ 104  µg/ml) and AFPIII (10-1  ~ 104  µg/ml) were added to the bull semen extender, respectively. Sperm kinematic parameters were measured to examine sperm toxicity and cryopreserved sperm quality. Measures of antioxidant activity such as superoxide dismutase (SOD), reduced glutathione/oxidative glutathione (GSH/GSSG), and total antioxidant capacity (TAC) were analysed to identify the effect of LeIBP on sperm quality. In addition, sperm viability was analysed using a flow cytometer and fluorescence microscope by SYBR14/PI staining. The results showed that the LeIBP groups (0.1, 1 and 10 µg/ml) were less toxic, and the quality of the sperm were dramatically improved in the extenders containing 0.1 µg/ml LeIBP among concentrations of LeIBP and AFPIII. The SOD activity of LeIBP was greater than that of AFPIII and control. In addition, sperm viability was enhanced in the LeIBP-treated group. In summary, LeIBP is a useful cryoprotective adjuvant for bull sperm cryopreservation, and the most efficient concentration of LeIBP is 0.1 µg/ml.

Comparison between pars plana and anterior endoscopic cyclophotocoagulation for the treatment of glaucoma.

IMPORTANCE: This is the first study to compare the efficacy and safety of endocyclophotocoagulation (ECP) via pars plana (ECP-plus) with ECP via limbus (anterior ECP) for treating glaucoma. BACKGROUND: There is no direct comparison of treatment outcomes between ECP-plus and anterior ECP. DESIGN: Retrospective study. PARTICIPANTS: Fifty-four consecutive patients. METHODS: Fifty-eight eyes from 54 consecutive patients underwent anterior ECP (33 eyes) or ECP-plus (25 eyes) with 2-year follow-up. Linear mixed model was used to analyse the surgical outcomes. MAIN OUTCOME MEASURES: Intraocular Pressure (IOP) was the primary outcome. Secondary outcomes were best-corrected visual acuity, number of glaucoma medications, complications and success rate. RESULTS: Compared to anterior ECP, patients in the ECP-plus group had lower IOP (estimate of effect size [EES] = -3.7 mmHg, P = 0.023) and used fewer number of glaucoma medications (EES = -1.11, P = 0.003), after adjusting for degrees of treatment, preoperative IOP, and presence of combined ECP and phacoemulsification procedure. Patients with ECP-plus achieved a higher success rate at 2 years postoperatively (80% vs 33.3%, P < 0.001). The decrease in IOP between the preoperative and last follow-up visit was greater in the ECP-plus group compared to the anterior ECP group (14.3 mmHg (52%) vs 5.2 mmHg (24%), P = 0.001). There was no significant difference in complication rates between the two groups (28% vs 33%, P = 0.561). CONCLUSIONS AND RELEVANCE: Anterior ECP and ECP-plus have a similar safety profile, and ECP-plus may offer superior IOP control for the management of glaucoma.

Stability of isoniazid injection in i.v. solutions.

PURPOSE: Results of an assessment of the chemical stability of isoniazid injection in 0.9% sodium chloride injection and 5% dextrose injection are reported. METHODS: Triplicate solutions of isoniazid (0.5 and 6.0 mg/mL) in the 2 diluents were prepared in ethylene and propylene copolymer i.v. containers and stored under light protection at room temperature (20-25 °C) or under refrigeration (2-8 °C). Standard aliquots were removed from each solution at time points up to 72 hours and analyzed via high-performance liquid chromatography (HPLC). Stability was defined as retention of >90% of the initial isoniazid concentration; pH, osmolality, and visual appearance were assessed. RESULTS: Isoniazid 0.5- and 6.0-mg/mL solutions in 0.9% sodium chloride injection were stable for up to 72 hours at room temperature or under refrigeration. HPLC analysis of isoniazid 0.5-mg/mL solutions in 5% dextrose injection revealed a decrease to less than 90% of the initial concentration at 8 hours at room temperature and at 30 hours under refrigeration. Isoniazid 6.0-mg/mL solutions in 5% dextrose injection were stable for 24 hours at room temperature and for 48 hours under refrigeration. The pH, osmolality, and visual appearance of the solutions were not affected. CONCLUSION: Isoniazid solutions of 0.5 and 6.0 mg/mL in 0.9% sodium chloride injection were stable under light protection for up to 72 hours when stored at room temperature or under refrigeration. Isoniazid injection was less stable in 5% dextrose injection, especially at a concentration of 0.5 mg/mL at room temperature.

Lauren Histologic Type Is the Most Important Factor Associated With Pattern of Recurrence Following Resection of Gastric Adenocarcinoma.

OBJECTIVE: To examine sites of initial recurrence in patients after resection of gastric and gastroesophageal junction Siewert II/III adenocarcinoma (GA). BACKGROUND: There are few recent studies on recurrence for Western patients following potentially curative resection of GA. METHODS: A review of a prospectively maintained, single institution database was performed. Clinicopathologic factors, site(s) of initial recurrence, disease-free survival, and overall survival were examined. RESULTS: From January 2000 to June 2010, 957 patients underwent potentially curative resection for GA, 435 patients (46%) had recurrent disease, and complete data on recurrence site(s) could be obtained in 386 patients. Tumors were Lauren intestinal type in 206 (53%) and diffuse or mixed-type in 180 (47%). Median time to recurrence was 12 months and 75% of recurrences occurred within 2 years. There was a significant difference in pattern of initial recurrence between the intestinal and diffuse/mixed cohorts (P < 0.001). For intestinal tumors, distant metastasis was the most common site (54%), followed by locoregional (20%), peritoneal (15%), and multifocal (11%). For diffuse/mixed tumors, peritoneal recurrence was the most common (37%), followed by distant (32%), locoregional (22%), and multifocal (9%). On multivariate analysis, Lauren histologic type was the only significant factor that was associated with both peritoneal recurrence (diffuse, hazard ratio 2.22, confidence interval 1.38-3.94) and distant recurrence (intestinal, hazard ratio 1.888, confidence interval 1.202-2.966). After recurrence, median overall survival was only 8.4 months. CONCLUSIONS: In GA patients who recur after resection, patterns of recurrence vary significantly based on Lauren histologic type.

Spatial distribution of polycyclic aromatic hydrocarbon and polychlorinated biphenyl sources in the Nakdong River Estuary, South Korea.

Our research team investigated the elemental composition and the presence of various toxic organic compounds, such as polycyclic aromatic hydrocarbons (PAHs) and polychlorinated biphenyls (PCBs), in estuary surface sediments to trace the spatial distribution of the sources of pollution deposited in Nakdong River, Busan, South Korea. The spatial patterns of elemental composition and toxic organic compounds were determined from the measurements of total organic carbon (TOC), total nitrogen, total sulfur, PAHs, and PCBs. The sediments had TOC contents of between 0.02 and 1.80 wt% (avg. 0.34 wt%), depending on the amount of clay-sized particles. The concentrations of PAHs and PCBs (10.8-167.7 ng g-1 dry wt and 197.0-754.0 pg g-1 dry wt, respectively) in surface sediments revealed different spatial patterns for these compounds, suggesting that they partially originated from the combustion of fossil fuels and from the use of commercial PCB products at adjacent industrial complexes. Although these concentrations were far below the Sediment Quality Guideline (SQG) of the National Oceanic and Atmospheric Administration (NOAA), the sediments at one site contained PCBs at concentrations close to the response level (754.0 pg g-1 dry wt), and were dominated by low-molecular-weight PAHs. The PAHs and PCBs in Nakdong River Estuary sediments were likely to have originated from the combustion of fossil fuels and biomass at the adjacent industrial complexes. The primarily analyzed results determined that PAHs originated from the combustion of fossil fuels and biomass, and overall concentrations were related to the contributions of individual PAHs in most sediment samples. Based on the SQG of the NOAA, our results indicate that the anthropogenic activity should be considered on the future-sustainable management of this estuary system.

Stability of tacrolimus solutions in polyolefin containers.

PURPOSE: Results of a study to determine the stability of tacrolimus solutions stored in polyolefin containers under various temperature conditions are reported. METHODS: Triplicate solutions of tacrolimus (0.001, 0.01, and 0.1 mg/mL) in 0.9% sodium chloride injection or 5% dextrose injection were prepared in polyolefin containers. Some samples were stored at room temperature (20-25 °C); others were refrigerated (2-8 °C) for 20 hours and then stored at room temperature for up to 28 hours. The solutions were analyzed by stability-indicating high-performance liquid chromatography (HPLC) assay at specified time points over 48 hours. Solution pH was measured and containers were visually inspected at each time point. Stability was defined as retention of at least 90% of the initial tacrolimus concentration. RESULTS: All tested solutions retained over 90% of the initial tacrolimus concentration at all time points, with the exception of the 0.001-mg/mL solution prepared in 0.9% sodium chloride injection, which was deemed unstable beyond 24 hours. At all evaluated concentrations, mean solution pH values did not change significantly over 48 hours; no particle formation was detected. CONCLUSION: During storage in polyolefin bags at room temperature, a 0.001-mg/mL solution of tacrolimus was stable for 24 hours when prepared in 0.9% sodium chloride injection and for at least 48 hours when prepared in 5% dextrose injection. Solutions of 0.01 and 0.1 mg/mL prepared in either diluent were stable for at least 48 hours, and the 0.01-mg/mL tacrolimus solution was also found to be stable throughout a sequential temperature protocol.

Audiologic presentation of enlargement of the vestibular aqueduct according to the SLC26A4 genotypes.

OBJECTIVES/HYPOTHESIS: To determine the distribution of the number and types of mutant alleles of SLC26A4 and their correlations with hearing phenotypes in Korean bilateral enlargement of vestibular aqueduct (EVA) patients. STUDY DESIGN: Prospective cohort study. METHODS: To determine the number and type of mutant alleles, Sanger sequencing of coding region of SLC26A4 was performed for 56 patients with bilateral EVA who were consecutively recruited. Their correlations with hearing phenotypes were analyzed based on 0.5-, 1-, 2-, and 3-kHz air conduction averages of pure-tone audiometry. RESULTS: Most patients with bilateral EVA (83.9%) carried two mutant alleles of SLC26A4 (M2), and all others (16.1%) had only one detectable mutant allele of SLC26A4 (M1) in the Korean population. There were no cases with zero mutations. p.H723R/p.H723R was the most frequently observed mutant allelic pair (34%), followed by p.H723R/c.919-2A>G (20%). There was no significant difference in hearing threshold, progression, or fluctuation of hearing level between the M1 and M2 groups. However, focusing on the type of mutations exclusively in the M2 group, cases with p.H723R/c.919-2A>G were associated with more frequent progression of hearing loss during the follow-up period. The cases with p.H723R/c.919-2A>G tended to show slightly better hearing than p.H723R homozygotes, although the difference was not statistically significant. There appears to be a different genotype-auditory phenotype correlation among ethnicities. CONCLUSIONS: Our data suggest that the auditory phenotype of Korean bilateral EVA patients is more strongly correlated with the type rather than the number of mutations in SLC26A4. LEVEL OF EVIDENCE: NA.

Organochlorine pesticides and polychlorinated biphenyls in Korean human milk: contamination levels and infant risk assessment.

The levels of persistent organic pollutants (POPs) were determined in 50 samples of Korean human milk. POPs include organochlorine pesticides (OCPs) [aldrin, chlordanes, dieldrin, dichlorodiphenyltrichloroethanes (DDTs), endrins, heptachlors, hexachlorobenzene (HCB), hexachlorocyclohexanes (HCHs), mirex, and toxaphenes] and marker PCBs (PCB28, PCB52, PCB101, PCB138, PCB153 and PCB180). In all samples, p,p'-DDE were determined as 75.5-1115.3 ng/g fat. The compounds ß-HCH and p,p'-DDT were detected at 72% and 60% of the samples, respectively. Chlordanes (nd-84.9 ng/g fat) heptachlors (nd-40.1 ng/g fat), HCB (nd-42.9 ng/g fat) and PCBs (nd-38.3 ng/g fat) were detected in several samples. The ratio of dichlorodiphenyltrichloroethylene (DDE)/DDT was 6.8, which explained that exposure of volunteers to DDT did not occur recently. Compared with the previous monitoring data, the level of marker PCBs generally decreased in the milk samples. The levels of OCPs are significantly correlated to the residential periods of the mothers but not with their dietary habits. Considering the daily intake of each OCPs, 18% of infants would ingest the amount of heptachlor exceeding the acceptable daily intake (ADI) proposed by World Health Organization (WHO). There was no sample surpassing the WHO ADI for DDTs, HCB and chlordanes.

Dynamic structural changes are observed upon collagen and metal ion binding to the integrin α1 I domain.

We have applied hydrogen-deuterium exchange mass spectrometry, in conjunction with differential scanning calorimetry and protein stability analysis, to examine solution dynamics of the integrin α1 I domain induced by the binding of divalent cations, full-length type IV collagen, or a function-blocking monoclonal antibody. These studies revealed features of integrin activation and α1I-ligand complexes that were not detected by static crystallographic data. Mg(2+) and Mn(2+) stabilized α1I but differed in their effects on exchange rates in the αC helix. Ca(2+) impacted α1I conformational dynamics without altering its gross thermal stability. Interaction with collagen affected the exchange rates in just one of three metal ion-dependent adhesion site (MIDAS) loops, suggesting that MIDAS loop 2 plays a primary role in mediating ligand binding. Collagen also induced changes consistent with increased unfolding in both the αC and allosteric C-terminal helices of α1I. The antibody AQC2, which binds to α1I in a ligand-mimetic manner, also reduced exchange in MIDAS loop 2 and increased exchange in αC, but it did not impact the C-terminal region. This is the first study to directly demonstrate the conformational changes induced upon binding of an integrin I domain to a full-length collagen ligand, and it demonstrates the utility of the deuterium exchange mass spectrometry method to study the solution dynamics of integrin/ligand and integrin/metal ion interactions. Based on the ligand and metal ion binding data, we propose a model for collagen-binding integrin activation that explains the differing abilities of Mg(2+), Mn(2+), and Ca(2+) to activate I domain-containing integrins.

Combination drug delivery approaches in metastatic breast cancer.

Disseminated metastatic breast cancer needs aggressive treatment due to its reduced response to anticancer treatment and hence low survival and quality of life. Although in theory a combination drug therapy has advantages over single-agent therapy, no appreciable survival enhancement is generally reported whereas increased toxicity is frequently seen in combination treatment especially in chemotherapy. Currently used combination treatments in metastatic breast cancer will be discussed with their challenges leading to the introduction of novel combination anticancer drug delivery systems that aim to overcome these challenges. Widely studied drug delivery systems such as liposomes, dendrimers, polymeric nanoparticles, and water-soluble polymers can concurrently carry multiple anticancer drugs in one platform. These carriers can provide improved target specificity achieved by passive and/or active targeting mechanisms.

Combining H/D exchange mass spectroscopy and computational docking reveals extended DNA-binding surface on uracil-DNA glycosylase.

X-ray crystallography provides excellent structural data on protein-DNA interfaces, but crystallographic complexes typically contain only small fragments of large DNA molecules. We present a new approach that can use longer DNA substrates and reveal new protein-DNA interactions even in extensively studied systems. Our approach combines rigid-body computational docking with hydrogen/deuterium exchange mass spectrometry (DXMS). DXMS identifies solvent-exposed protein surfaces; docking is used to create a 3-dimensional model of the protein-DNA interaction. We investigated the enzyme uracil-DNA glycosylase (UNG), which detects and cleaves uracil from DNA. UNG was incubated with a 30 bp DNA fragment containing a single uracil, giving the complex with the abasic DNA product. Compared with free UNG, the UNG-DNA complex showed increased solvent protection at the UNG active site and at two regions outside the active site: residues 210-220 and 251-264. Computational docking also identified these two DNA-binding surfaces, but neither shows DNA contact in UNG-DNA crystallographic structures. Our results can be explained by separation of the two DNA strands on one side of the active site. These non-sequence-specific DNA-binding surfaces may aid local uracil search, contribute to binding the abasic DNA product and help present the DNA product to APE-1, the next enzyme on the DNA-repair pathway.

Synthesis and in vitro characterization of semitelechelic poly[N-(2-hydroxypropyl)methacrylamide]-trastuzumab conjugates targeted to breast cancer.

Trastuzumab (TRZ) is a humanized monoclonal antibody that targets the extracellular domain of the human epidermal growth factor receptor type 2 (Her2). Semitelechelic (ST) poly[N-(2-hydroxypropyl)methacrylamide]-TRZ conjugates are successfully synthesized and evaluated as a potential drug delivery system that actively targets Her2-overexpressing cancer cells. The ST backbone shows favorable characteristics when conjugated to TRZ. The conjugate exhibits comparable and prolonged anticancer activity when compared to free TRZ in Her2 overexpressing breast cancer cell lines.

The amino terminus of cGMP-dependent protein kinase Iß increases the dynamics of the protein's cGMP-binding pockets.

The type I cGMP-dependent protein kinases play critical roles in regulating vascular tone, platelet activation and synaptic plasticity. PKG I α and PKG Iß differ in their first ~100 amino acids giving each isoform unique dimerization and autoinhibitory domains with identical cGMP-binding pockets and catalytic domains. The N-terminal leucine zipper and autoinhibitory domains have been shown to mediate isoform specific affinity for cGMP. PKG Iα has a >10 fold higher affinity for cGMP than PKG Iß, and PKG Iß that is missing its leucine zipper has a three-fold decreased affinity for cGMP. The exact mechanism through which the N-terminus of PKG alters cGMP-affinity is unknown. In the present study, we have used deuterium exchange mass spectrometry to study how PKG Iß's N-terminus affects the conformation and dynamics of its cGMP-binding pockets. We found that the N-terminus increases the rate of deuterium exchange throughout the cGMP-binding domain. Our results suggest that the N-terminus shifts the conformational dynamics of the binding pockets, leading to an "open" conformation that has an increased affinity for cGMP.

Role of narrow band imaging for diagnosis of early-stage esophagogastric cancer: current consensus of experienced endoscopists in Asia-Pacific region.

In Asian countries, squamous cell carcinoma is the most common type of esophageal cancer, and the incidence of gastric cancer remains have plateaued. To synthesize current information and to illustrate its clinical benefit of narrow band imaging (NBI) for diagnosis of superficial esophageal squamous carcinoma (SESCC) and early gastric cancer (EGC), a consensus conference was held by a panel of nine experts from Asian-Pacific countries. The expert's agreement suggested importance of interpretation of both vascular architecture and surface structure of the lesions and proper processor settings for endoscopic images. Zoom endoscopy was not regarded as absolutely necessary for detection of SESCC, but magnifying observation provided valuable information for characterization of detected lesions in the esophagus and the stomach. In general, NBI is useful for detection and characterization of SESCC, whereas it is beneficial mainly for characterization of EGC. Chromoendoscopy was found to be still worthwhile in certain situations, such as determination of the extent of SESCC by Lugol's staining, or detection and delineation of EGC by indigo carmine. NBI could replace chromoendoscopy in routine examination because it is easy to use and adds much information to conventional WLI, but it cannot eliminate chromoendoscopy when we make a final diagnosis for treatment decision-making. Consequently, the benefit of NBI or magnifying NBI is specific for the organ and the purpose of the examination, thus optimum indication and usage should be understood for maximum clinical benefit.

Characterization of synthetic nanocrystalline mackinawite: crystal structure, particle size, and specific surface area.

Iron sulfide was synthesized by reacting aqueous solutions of sodium sulfide and ferrous chloride for 3 days. By X-ray powder diffraction (XRPD), the resultant phase was determined to be primarily nanocrystalline mackinawite (space group: P4/nmm) with unit cell parameters a = b = 3.67 Å and c = 5.20 Å. Iron K-edge XAS analysis also indicated the dominance of mackinawite. Lattice expansion of synthetic mackinawite was observed along the c-axis relative to well-crystalline mackinawite. Compared with relatively short-aged phase, the mackinawite prepared here was composed of larger crystallites with less elongated lattice spacings. The direct observation of lattice fringes by HR-TEM verified the applicability of Bragg diffraction in determining the lattice parameters of nanocrystalline mackinawite from XRPD patterns. Estimated particle size and external specific surface area (SSA(ext)) of nanocrystalline mackinawite varied significantly with the methods used. The use of Scherrer equation for measuring crystallite size based on XRPD patterns is limited by uncertainty of the Scherrer constant (K) due to the presence of polydisperse particles. The presence of polycrystalline particles may also lead to inaccurate particle size estimation by Scherrer equation, given that crystallite and particle sizes are not equivalent. The TEM observation yielded the smallest SSA(ext) of 103 m(2)/g. This measurement was not representative of dispersed particles due to particle aggregation from drying during sample preparation. In contrast, EGME method and PCS measurement yielded higher SSA(ext) (276-345 m(2)/g by EGME and 424 ± 130 m(2)/g by PCS). These were in reasonable agreement with those previously measured by the methods insensitive to particle aggregation.