Clinical activity of fulvestrant in metastatic breast cancer previously treated with endocrine therapy and/or chemotherapy

( Mi Hwa Heo ),( Hee Kyung Kim ),( Hansang Lee ),( Ji-yeon Kim ),( Jin-seok Ahn ),( Young-hyuck Im ),( Yeon Hee Park ) 대한내과학회 2019 The Korean Journal of Internal Medicine Vol.34 No.5

Background/Aims: We conducted a retrospective analysis of the clinical activity of fulvestrant in postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) previously treated with endocrine therapy and/or chemotherapy. Methods: We reviewed the medical records of all patients with MBC treated at Samsung Medical Center between January 2009 and August 2016. Patients received fulvestrant 250 mg intramuscularly every 28 days (from January 2009 to November 2010) or 500 mg intramuscularly every 28 days (from December 2010 to August 2016). Tumor responses were assessed every 8 weeks and at the end of treatment, as well as when disease progression was suspected. Results: A total of 84 patients were included in this study. A median of two previous endocrine treatments had been performed; 79% of the patients had received two or more endocrine treatments. Forty-five patients (54%) had been treated with chemotherapy for MBC before the fulvestrant treatment course. Visceral metastasis was found in 49 patients (58%). The estimated median progression-free survival and overall survival were 4.4 months (95% confidence interval [CI], 3.4 to 5.5) and 32.5 months (95% CI, 17.6 to 47.4), respectively. The disease control rate was 40.5% (95% CI, 30.5 to 51.5); partial response was observed in 16% of the patients and stable disease was observed in 25% of the patients. The most frequently reported adverse reactions were mild-to-moderate grade myalgia (10.5% of the patients), injection site pain (7%), and fatigue (7%). Fulvestrant was generally well tolerated. Conclusions: Fulvestrant showed encouraging clinical activity and favorable feasibility in postmenopausal women with MBC who had been treated with multiple endocrine therapies and/or cytotoxic chemotherapies.

Analgesic effect of quetiapine in a mouse model of cancer-induced bone pain

( Mi Hwa Heo ),( Jin Young Kim ),( Ilseon Hwang ),( Eunyoung Ha ),( Keon Uk Park ) 대한내과학회 2017 The Korean Journal of Internal Medicine Vol.32 No.6

Background/Aims: Cancer-induced bone pain (CIBP) is one of the most common pains in patients with advanced neoplasms. Because of treatment-associated side effects, more than half of cancer patients are reported to have inadequate and undermanaged pain control. New mechanism-based therapies must be developed to reduce cancer pain. Quetiapine is a commonly used atypical antipsychotic drug. We report a study of the potential analgesic effects of quetiapine in a mouse model of CIBP and examine the mechanism of bone pain by analyzing the expression of various nociceptors. Methods: Fifteen male C₃H/HeN mice were arbitrarily divided into five groups: control and, CIBP with no treatment, quetiapine treatment, opioid treatment, and melatonin treatment. The mice were tested for mechanical hyperalgesia by determining the nociceptive hind paw withdrawal pressure threshold. Tissues from tibia were removed and subjected to quantitative and qualitative evaluations of transient receptor potential vanilloid ₁ (TRPV₁), TRPV₄, acid-sensing ion channel ₁ (ASIC₁), ASIC₂, and ASIC₃ expression. Results: Paw withdrawal pressure threshold was improved in the quetiapine treatment group compared with the CIBP group. Expression of TRPV₁, TRPV₄, ASIC₁, ASIC₂, and ASIC₃ in the CIBP with quetiapine treatment group was significantly lower than that in the CIBP group. Conclusions: Our results suggest an analgesic effect of quetiapine in the CIBP animal model and implicate TRPV and ASICs as potential targets for cancer pain management.

활기찬 노후를 위한 마을의 고령친화성 향상 방안

허미화(MI Hwa Heo),김영정(Young Jeong Kim) 서울시 여성가족재단 2017 서울시 여성가족재단 연구사업보고서 Vol.- No.-

제주도에서 브루셀라에 의해 발생한 특발성 세균성 복막염

허상택,조유경,김영리,이근화,윤지완,고관수,박미연,최영실 대한감염학회 2007 감염과 화학요법 Vol.39 No.1

Spontaneous bacterial peritonitis is the common infectious disease in liver cirrhosis patients with a fever. Brucellosis is a rare cause of bacterial peritonitis. A case indigenous to a citizen of Jeju, he ate a raw veal of cow four times in last 2 months prior to admission. The gram-negative bacilli were isolated from blood and peritoneal fluid cultures. He was confirmed brucellosis by serologic work- ups. This isolate was confirmed as Brucella abortus by using PCR amplification of 16S ribosomal RNA (rRNA) and omp2. This is the first case of bruellosis that was diagnosed spontaneous bacterial peritonitis in liver cirrhosis patient among native korean citizens. Successful treatment was obtained by using a regimen of doxycycline and gentamicin. Brucella should be suspected as a cause of spontaneous bacterial peritonitis in cirrhotic patients with no response to standard spontaneous bacterial peritonitis treatments. 브루셀라증은 전 세계적으로 발생하는 인수공통 전염병중의 하나로, 국내에서도 해마다 환자가 증가하고 있는 상황이다. 본 증례는 간경화 환자에서 환자의 잘못된 지식을 바탕으로 소 태아 육회를 섭취한 이후 복수와 발열을 주소로 내원한 환자이다. 상기 과거력이 환자의 질환과의 직접적인 연관성을 밝히기는 어려우나 환자의 진단을 추정하는데 도움이 되었으며, 이러한 가능성을 배제하기 위해서라도 국내 유통에 있어서 좀더 적극적인 대체가 필요하다 하겠다. 상기 환자는 브루셀라에 의해 발생한 특발성 세균성 복막염 환자로 제주도에서 발생한 내국인의 첫 증례이기에 문헌 고찰과 함께 보고하는 바이다.

Shape-controlled assemblies of graphitic carbon nitride polymer for efficient sterilization therapies of water microbial contamination via 2D g-C₃N₄ under visible light illumination

Heo, Nam Su,Shukla, Shruti,Oh, Seo Yeong,Bajpai, Vivek K.,Lee, Sun Uk,Cho, Hye-Jin,Kim, Suji,Kim, Yeonho,Kim, Hae Jin,Lee, Sang Yup,Jun, Young-Si,Oh, Mi-Hwa,Han, Young-Kyu,Yoo, Seung Min,Huh, Yun Suk Elsevier 2019 Materials Science and Engineering C Vol. No.

<P><B>Abstract</B></P> <P>Bacterial pathogens of water origin have potential public threats thus suggesting the need of developing efficient and sustainable water disinfection strategies from waterborne pathogens. We set out to synthesize different controlled morphologies of graphitic carbon nitride (g-C<SUB>3</SUB>N<SUB>4</SUB>) polymer, evaluate their comparative effects on the generation of reactive oxygen species (ROS), and investigate potential applications in water purification systems. Characterization of the synthesized microstructures of g-C<SUB>3</SUB>N<SUB>4</SUB>, such as melamine-cyanuric acid (MCA)-based rosette-type, rod-type, 2D hexagonal, and 3D cubic mesoporous silica was accomplished using Fourier transform infrared (FT-IR), energy dispersive spectroscopy (EDS), scanning electron microscopy (SEM), X-ray diffractometry (XRD), and transmission electron microscopy (TEM). The microbial inhibitory potential of 2D g-C<SUB>3</SUB>N<SUB>4</SUB> photocatalyst against waterborne <I>Escherichia coli</I>, <I>Staphylococcus aureus</I>, and <I>Salmonella typhimurium</I> was evaluated based on the effective activity of 2D g-C<SUB>3</SUB>N<SUB>4</SUB> upon visible light excitations. The microbicidal efficiency of 2D g-C<SUB>3</SUB>N<SUB>4</SUB> was evident within 30 min of visible light exposure via direct interaction, while other microstructures of g-C<SUB>3</SUB>N<SUB>4</SUB> demonstrated only slight antimicrobial effects after 120 min, with insufficient ROS generation. The antimicrobial and ROS-generating effects of 2D g-C<SUB>3</SUB>N<SUB>4</SUB> depended on the type and surface area of the synthesized 2D g-C<SUB>3</SUB>N<SUB>4</SUB> material. Considering its availability and excellent disinfection activity, 2D g-C<SUB>3</SUB>N<SUB>4</SUB> obtained from simple and convenient facile synthesis is a promising solar-driven photocatalyst for clearing microbial contamination from water.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Waterborne pathogenic bacteria pose significant health risks to the public. </LI> <LI> We synthesized different morphologies of graphitic carbon nitride (g-C<SUB>3</SUB>N<SUB>4</SUB>) polymer. </LI> <LI> Synthesized microstructures of g-C<SUB>3</SUB>N<SUB>4</SUB> had potential effect on ROS generation. </LI> <LI> 2D hexagonal g-C<SUB>3</SUB>N<SUB>4</SUB> exhibited significant antimicrobial potential. </LI> <LI> 2D g-C<SUB>3</SUB>N<SUB>4</SUB> had photocatalytic inactivation efficiency in a water purifying system. </LI> </UL> </P>

Toward redesigning the PEG surface of nanocarriers for tumor targeting: impact of inner functionalities on size, charge, multivalent binding, and biodistribution

Heo, Ju Young,Kang, Se Hun,Kim, Young-Hwa,You, Suyeon,Jin, Kyeong Sik,Kim, Seung Won,Jung, Hye-youn,Jung, Kyung Oh,Lee, Chul-Hee,Kim, Mi Jung,Sung, Soo-Eun,Kim, Boram,Choi, Insung S.,Youn, Hyewon,Chun Royal Society of Chemistry 2017 Chemical science Vol.8 No.7

<▼1><P>A simple strategy to enhance the tumor-targeting efficiency of PEGylated nanocarriers is demonstrated.</P></▼1><▼2><P>Achieving accurate and efficacious tumor targeting with minimal off-target effects is of paramount importance in designing diagnostic and therapeutic agents for cancer. In this respect, nanocarriers have gained enormous popularity because of their attainable multifunctional features, as well as tumor-targeting potential by extravasation. However, once administered into the bloodstream, nanocarriers face various <I>in vivo</I> obstacles that may significantly impair their performance needed for clinical translation. Herein, we demonstrate a strategy to enhance tumor-targeting efficiency by embedding functionalities in the interior region of partially PEGylated nanocarriers (<I>ca.</I> 10 nm in diameter), intended for active or passive targeting. The cooperative impact of these topologically inner functional groups (IFGs) was marked: enhancements of >100-fold in IC<SUB>50</SUB><I>in vitro</I> (<I>e.g.</I>, a high-avidity ligand with cationic IFGs) and >2-fold in tumor accumulation at 2 h post-injection <I>in vivo</I> (<I>e.g.</I>, a high-avidity ligand with anionic IFGs), both against the fully PEGylated counterpart. Analogous to allosteric modulators, properly employed IFGs may substantially improve the process of effectively directing nanocarriers to tumors, which is otherwise solely dependent on avidity or extravasation.</P></▼2>

CT-based quantitative evaluation of radiation-induced lung fibrosis: a study of interobserver and intraobserver variations

Heo, Jaesung,Cho, Oyeon,Noh, O Kyu,O, Young-Taek,Chun, Mison,Kim, Mi-Hwa,Park, Hae-Jin The Korean Society for Radiation Oncology 2014 Radiation Oncology Journal Vol.32 No.1

Purpose: The degree of radiation-induced lung fibrosis (RILF) can be measured quantitatively by fibrosis volume (VF) on chest computed tomography (CT) scan. The purpose of this study was to investigate the interobserver and intraobserver variability in CT-based measurement of VF. Materials and Methods: We selected 10 non-small cell lung cancer patients developed with RILF after postoperative radiation therapy (PORT) and delineated VF on the follow-up chest CT scanned at more than 6 months after radiotherapy. Three radiation oncologists independently delineated VF to investigate the interobserver variability. Three times of delineation of VF was performed by two radiation oncologists for the analysis of intraobserver variability. We analysed the concordance index (CI) and inter/intra-class correlation coefficient (ICC). Results: The median CI was 0.61 (range, 0.44 to 0.68) for interobserver variability and the median CIs for intraobserver variability were 0.69 (range, 0.65 to 0.79) and 0.61(range, 0.55 to 0.65) by two observers. The ICC for interobserver variability was 0.974 (p < 0.001) and ICCs for intraobserver variability were 0.996 (p < 0.001) and 0.991 (p < 0.001), respectively. Conclusion: CT-based measurement of VF with patients who received PORT was a highly consistent and reproducible quantitative method between and within observers.

Chromogenic Tubular Polydiacetylenes from Topochemical Polymerization of Self-Assembled Macrocyclic Diacetylenes

Heo, Jung-Moo,Kim, Youngmee,Han, Seulki,Joung, Joonyoung F.,Lee, Sang-hwa,Han, Sejin,Noh, Jaegeun,Kim, Jaeyong,Park, Sungnam,Lee, Haiwon,Choi, Yoon Mi,Jung, Young-Sik,Kim, Jong-Man American Chemical Society 2017 Macromolecules Vol.50 No.3

<P>Tubular materials formed by self-assembly of small organic molecules find great utility in chemical and material science. Conventional tubular structures often lack stability because non covalent molecular interactions are responsible for their conformational integrities. Herein we report the development of covalently linked chromogenic organic nanotubes which are prepared by using topochemical polymerization of self-assembled macrocyclic diacetylenes (MCDAs). Crystal structures of five MCDAs having different diameters were elucidated, and four of these substances were transformed to tubular polydiacetylenes (PDA) by UV-induced polymerization. Surprisingly, MCDA-1 was found to self-assemble in stacks with a tilt angle of 62.1 degrees which significantly deviates from the optimal value for polymerization of 45 degrees. This observation suggests that geometric parameters derived using linear diacetylene (DA) models might not be strictly applicable to polymerization of MCDA systems. Blue-phase PDAs obtained by polymerization of MCDA-1 and MCDA-3 have different thermochromic and solvatochromic properties, which enable them to be utilized for colorimetric differentiation of aromatic solvents including isomeric xylenes. The observations made and information obtained in this study should enhance the understanding and design of stimulus-responsive rigid organic nanotubes.</P>

A Case of Posterior Mediastinal Plasmacytoma Confounded by Community-Acquired Pneumonia

Heo, Dahee,Boo, Ki Yung,Jwa, Hyeyoung,Lee, Hwa Young,Kim, Jihyun,Kim, Seong Taeg,Seo, Hye Mi,Han, Sang Hoon,Maeng, Young-Hee,Lee, Jong Hoo The Korean Academy of Tuberculosis and Respiratory 2015 Tuberculosis and Respiratory Diseases Vol.78 No.3

Plasmacytomas are extramedullary accumulations of plasma cells originating from soft tissue. Mediastinal plasmacytoma is a rare presentation. A 67-year-old man recovered after antibiotic treatment for community-acquired pneumonia. However, on convalescent chest radiography after 3 months, mass like lesion at the right lower lung field was newly detected. Follow-up chest computed tomography (CT) revealed an increase in the extent of the right posterior mediastinal mass that we had considered to be pneumonic consolidations on previous CT scans. Through percutaneous needle biopsy, we diagnosed IgG kappa type extramedullary plasmacytoma of the posterior mediastinum.

CT-based quantitative evaluation of radiation-induced lung fibrosis: a study of interobserver and intraobserver variations

Jaesung Heo,Oyeon Cho,O Kyu Noh,Young-Taek Oh,Mison Chun,Mi-Hwa Kim,Hae-Jin Park 대한방사선종양학회 2014 Radiation Oncology Journal Vol.32 No.1

Purpose: The degree of radiation-induced lung fibrosis (RILF) can be measured quantitatively by fibrosis volume (VF) on chest computed tomography (CT) scan. The purpose of this study was to investigate the interobserver and intraobserver variability in CT-based measurement of VF. Materials and Methods: We selected 10 non-small cell lung cancer patients developed with RILF after postoperative radiation therapy (PORT) and delineated VF on the follow-up chest CT scanned at more than 6 months after radiotherapy. Three radiation oncologists independently delineated VF to investigate the interobserver variability. Three times of delineation of VF was performed by two radiation oncologists for the analysis of intraobserver variability. We analysed the concordance index (CI) and inter/intra-class correlation coefficient (ICC). Results: The median CI was 0.61 (range, 0.44 to 0.68) for interobserver variability and the median CIs for intraobserver variability were 0.69 (range, 0.65 to 0.79) and 0.61(range, 0.55 to 0.65) by two observers. The ICC for interobserver variability was 0.974 (p < 0.001) and ICCs for intraobserver variability were 0.996 (p < 0.001) and 0.991 (p < 0.001), respectively. Conclusion: CT-based measurement of VF with patients who received PORT was a highly consistent and reproducible quantitative method between and within observers.