Optical Imaging of Cancer-Related Proteases Using Near-Infrared Fluorescence Matrix Metalloproteinase-Sensitive and Cathepsin B-Sensitive Probes

Cathepsin B and matrix metalloproteinase (MMP) play key roles in tumor progression by controlled degradation of extracellular matrix. Consequently, these proteases have been attracted in cancer research, and many imaging probes utilizing these proteases have been developed. Our groups developed cathepsin B and MMP imaging nanoprobes based on polymer nanoparticle platform. Both cathepsin B and MMP imaging probes used near-infrared fluorescence (NIRF) dye and dark-quencher to for high sensitivity, and protease-sensitive peptide sequence in each probe authorized high specificity of the probes. We compared the bioactivities of cathepsin B and MMP sensitive probes in cancer-related environments to investigate the biological property of the probes. As a result, cathepsin B probe showed fluorescence recovery after the probe entered the cytoplasm. This property could be useful to evaluate the cytoplasmic targeted delivery by using probe-conjugated nanoparticles in vivo. On the other hand, MMP probe was superior in specificity in vivo and tissue study. This comparative study will provide precise information about peptide-based optical probes, and allow their proper application to cancer diagnosis

Growth rate of early-stage hepatocellular carcinoma in patients with chronic liver disease

Background/AimsThe goal of this study was to estimate the growth rate of hepatocellular carcinoma (HCC) and identify the host factors that significantly affect this rate.MethodsPatients with early-stage HCC (n=175) who underwent two or more serial dynamic imaging studies without any anticancer treatment at two tertiary care hospitals in Korea were identified. For each patient, the tumor volume doubling time (TVDT) of HCC was calculated by comparing tumor volumes between serial imaging studies. Clinical and laboratory data were obtained from the medical records of the patients.ResultsThe median TVDT was 85.7 days, with a range of 11 to 851.2 days. Multiple linear regression revealed that the initial tumor diameter (a tumor factor) and the etiology of chronic liver disease (a host factor) were significantly associated with the TVDT. The TVDT was shorter when the initial tumor diameter was smaller, and was shorter in HCC related to hepatitis B virus (HBV) infection than in HCC related to hepatitis C virus (HCV) infection (median, 76.8 days vs. 137.2 days; P=0.0234).ConclusionsThe etiology of chronic liver disease is a host factor that may significantly affect the growth rate of early-stage HCC, since HBV-associated HCC grows faster than HCV-associated HCC

Reduced Dose Intensity FOLFOX-4 as First Line Palliative Chemotherapy in Elderly Patients with Advanced Colorectal Cancer

To evaluate the toxicity and efficacy of a reduced dose intensity (mini-) FOLFOX-4 regimen as a first-line palliative chemotherapy in elderly patients (≥70 yr of age) with advanced colorectal cancer, data from prospective databases at Seoul National University Bundang Hospital and Seoul Municipal Boramae Hospital were analyzed. A total of 20 patients were enrolled between January 2001 and August 2004, and were treated with oxaliplatin 65 mg/m2 on day 1, and with 2-hr infusions of leucovorin 150 mg/m2 followed by a 5-FU bolus (300 mg/m2) and 22-hr continuous infusions (450 mg/m2) for 2 consecutive days every 2 weeks until progression, unacceptable toxicity or patient refusal. Sixteen patients were evaluable for response with an overall response rate of 43.8%. Median progression-free survival was 4.8 months (95% CI: 3.0-6.7) and overall survival was 13.5 months (95% CI: 11.1-16.0). The main side effects were anemia and neutropenia, which were observed in 20.8% and 17.7%, respectively, of the total cycles administered. There were no grade 4 toxicities and only one patient suffered from febrile neutropenia. No grade 3 toxicities occurred except for anemia (5.2%) and vomiting (1.0%). In conclusion, the mini-FOLFOX-4 regimen was found to be well tolerated with acceptable toxicity, and to provide a benefit for elderly patients with colorectal cancer

Reliability and Validity of the Korean Cancer Pain Assessment Tool (KCPAT)

The Korean Cancer Pain Assessment Tool (KCPAT), which was developed in 2003, consists of questions concerning the location of pain, the nature of pain, the present pain intensity, the symptoms associated with the pain, and psychosocial/spiritual pain assessments. This study was carried out to evaluate the reliability and validity of the KCPAT. A stratified, proportional-quota, clustered, systematic sampling procedure was used. The study population (903 cancer patients) was 1% of the target population (90,252 cancer patients). A total of 314 (34.8%) questionnaires were collected. The results showed that the average pain score (5 point on Likert scale) according to the cancer type and the at-present average pain score (VAS, 0-10) were correlated (r=0.56, p<0.0001), and showed moderate agreement (kappa=0.364). The mean satisfaction score was 3.8 (1-5). The average time to complete the questionnaire was 8.9 min. In conclusion, the KCPAT is a reliable and valid instrument for assessing cancer pain in Koreans

Association between anti-Porphyromonas gingivalis or anti-α-enolase antibody and severity of periodontitis or rheumatoid arthritis (RA) disease activity in RA

This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.Abstract Background Periodontitis (PD) has been reported to be associated with rheumatoid arthritis (RA). Porphyromonas gingivalis (P. gingivalis) is a gram-negative anaerobic bacterium that is recognized as one of the major pathogenic organisms in PD and is the only bacterium known to express peptidylarginine deiminase (PAD). Antibody against human α-enolase (ENO1) is one of the autoantibodies in RA. ENO1 is a highly conserved protein, and could be a candidate molecule for molecular mimicry between bacterial and human proteins. In the present study, we measured serum antibody against P. gingivalis and human ENO1 in patients with RA and investigated their association with the severity of PD or disease activity of RA. Methods Two hundred, forty-eight patients with RA and 85 age- and sex-matched healthy controls were evaluated by rheumatologic and periodontal examinations. The serum levels of anti-P. gingivalis and anti-ENO1 antibodies were measured by an enzyme-linked immunosorbent assay (ELISA). Results Patients with RA had significantly higher levels of anti-P. gingivalis and anti-ENO1 antibody titers than the controls (p = 0.002 and 0.0001, respectively). Anti-P. gingivalis antibody titers significantly correlated with anti-ENO1 antibody titers in RA patients (r = 0.30, p < 0.0001). There were significant correlations between anti-P. gingivalis antibody titers and the gingival index (GI), probing pocket depth (PPD), bleeding on probing (BOP) and clinical attachment level (CAL) (p = 0.038, 0.004, 0.004 and 0.002, respectively) in RA. Anti-P. gingivalis antibody titers were not correlated with disease activity score 28 (DAS28) or anti-CCP titer. However, anti-ENO1 antibody titers were significantly correlated not only with the periodontal indices, such as PPD, BOP, and CAL (p = 0.013, 0.023 and 0.017, respectively), but also RA clinical characteristics, such as DAS28, anti-CCP titer, and ESR (p = 0.009, 0.015 and 0.001, respectively). Conclusion Anti-P. gingivalis and anti-ENO1 antibody titers were correlated with the severity of PD in RA. Anti-ENO1 antibody titers, but not anti-P. gingivalis antibody titers, were further associated with RA disease activity

Serum immunoglobulin fused interferon-α inhibited tumor growth in athymic mice bearing colon 26 adenocarcinoma cells

Interferon (IFN) has therapeutic potential for a wide range of infectious and proliferative disorders. However, the half-life of IFN is too short to have a stable therapeutic effect. To overcome this problem, serum immunoglobulin has been fused to IFN. In this study, the efficacy of serum immunoglobulin fused INFs (si-IFN1 and si-IFN2) was evaluated on athymic mice bearing colon 26 adenocarcinoma cells. Seven days after the implantation of tumor cells, each group of mice was injected once a week with si-IFN1 and si-IFN2 at two different concentrations (10 × : 30 µg/kg and 50 × : 150 µg/kg). A slight anti-tumoral effect was observed in all 10 × groups compared to the control. In the 50 × groups, however, si-IFN1 and si-IFN2 showed significant anti- tumoral effects compared to the control. To gain more information on the mechanisms associated with the decrease of tumor size, a Western blot assay of apoptosis-related molecules was performed. The protein expression of cytochrome c, caspase 9, 6, and 3 were increased by si-IFN1 and si-IFN2. These 2 IFNs also increased the expressions of p53, p21, Bax and Bad. Interestingly, si-IFN1 and si-IFN2 decreased the expression of VEGF-β. Taken together, serum immunoglobulin fused IFNs increased therapeutic efficacy under current experimental condition

Individualized Tumor Response Testing for Prediction of Response to Paclitaxel and Cisplatin Chemotherapy in Patients with Advanced Gastric Cancer

The purpose of our study was to determine the most accurate analytic method to define in vitro chemosensitivity, using clinical response as reference standard in prospective clinical trial, and to assess accuracy of adenosine triphosphate-based chemotherapy response assay (ATP-CRA). Forty-eight patients with chemo-naïve, histologically confirmed, locally advanced or metastatic gastric cancer were enrolled for the study and were treated with combination chemotherapy of paclitaxel 175 mg/m2 and cisplatin 75 mg/m2 for maximum of six cycles after obtaining specimen for ATP-CRA. We performed the receiver operator characteristic curve analysis using patient responses by WHO criteria and ATP-CRA results to define the method with the highest accuracy. Median progression free survival was 4.2 months (95% confidence interval [CI]: 3.4-5.0) and median overall survival was 11.8 months (95% CI: 9.7-13.8) for all enrolled patients. Chemosensitivity index method yielded highest accuracy of 77.8% by ROC curve analysis, and the specificity, sensitivity, positive and negative predictive values were 95.7%, 46.2%, 85.7%, and 75.9%. In vitro chemosensitive group showed higher response rate (85.7% vs. 24.1%) (P=0.005) compared to chemoresistant group. ATP-CRA could predict clinical response to paclitaxel and cisplatin chemotherapy with high accuracy in advanced gastric cancer patients. Our study supports the use of ATP-CRA in further validation studies

Immunogenicity of influenza vaccination in patients with cancer receiving immune checkpoint inhibitors

Among prospectively enrolled adult patients with cancer receiving immune checkpoint inhibitors (ICIs; n = 46) or cytotoxic agents (n = 90), seroprotection and seroconversion rates after seasonal quadrivalent influenza vaccinations were higher with ICI than with cytotoxic chemotherapy. These results support annual influenza vaccinations for cancer patients receiving ICIs.