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Clinicopathological Characteristics of Triple Negative Breast Cancer at a Tertiary Care Hospital in India

  • Dogra, Atika;Doval, Dinesh Chandra;Sardana, Manjula;Chedi, Subhash Kumar;Mehta, Anurag
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.24
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    • pp.10577-10583
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    • 2015
  • Background: Triple-negative breast cancer (TNBC), characterized by the lack of expression of estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2, is typically associated with a poor prognosis. The majority of TNBCs show the expression of basal markers on gene expression profiling and most authors accept TNBC as basal-like (BL) breast cancer. However, a smaller fraction lacks a BL phenotype despite being TNBC. The literature is silent on non-basal-like (NBL) type of TNBC. The present study was aimed at defining behavioral differences between BL and NBL phenotypes. Objectives: i) Identify the TNBCs and categorize them into BL and NBL breast cancer. ii) Examine the behavioral differences between two subtypes. iii) Observe the pattern of treatment failure among TNBCs. Materials and Methods: All TNBC cases during January 2009-December 2010 were retrieved. The subjects fitting the inclusion criteria of study were differentiated into BL and NBL phenotypes using surrogate immunohistochemistry with three basal markers $34{\beta}E12$, c-Kit and EGFR as per the algorithm defined by Nielsen et al. The detailed data of subjects were collated from clinical records. The comparison of clinicopathological features between two subgroups was done using statistical analyses. The pattern of treatment failure along with its association with prognostic factors was assessed. Results: TNBC constituted 18% of breast cancer cases considered in the study. The BL and NBL subtypes accounted for 81% and 19% respectively of the TNBC group. No statistically significant association was seen between prognostic parameters and two phenotypes. Among patients with treatment failure, 19% were with BL and 15% were with NBL phenotype. The mean disease free survival (DFS) in groups BL and NBL was 30.0 and 37.9 months respectively, while mean overall survival (OS) was 31.93 and 38.5 months respectively. Treatment failure was significantly associated with stage (p=.023) among prognostic factors. Conclusions: Disease stage at presentation is an important prognostic factor influencing the treatment failure and survival among TNBCs. Increasing tumor size is related to lymph node positivity. BL tumors have a more aggressive clinical course than that of NBL as shown by shorter DFS and OS, despite having no statistically significant difference between prognostic parameters. New therapeutic alternatives should be explored for patients with this subtype of breast cancer.

Microbiology and Epidemiology of Infectious Spinal Disease

  • Jeong, Se-Jin;Choi, Seung-Won;Youm, Jin-Young;Kim, Hyun-Woo;Ha, Ho-Gyun;Yi, Jin-Seok
    • Journal of Korean Neurosurgical Society
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    • v.56 no.1
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    • pp.21-27
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    • 2014
  • Objective : Infectious spinal disease is regarded as an infection by a specific organism that affects the vertebral body, intervertebral disc and adjacent perivertebral soft tissue. Its incidence seems to be increasing as a result of larger proportion of the older patients with chronic debilitating disease, the rise of intravenous drug abuser, and the increase in spinal procedure and surgery. In Korea, studies assessing infectious spinal disease are rare and have not been addressed in recent times. The objectives of this study are to describe the epidemiology of all kind of spinal infectious disease and their clinical and microbiological characteristics as well as to assess the diagnostic methodology and the parameters related to the outcomes. Methods : A retrospective study was performed in all infectious spinal disease cases presenting from January 2005 to April 2010 to three tertiary teaching hospitals within a city of 1.5 million in Korea. Patient demographics, risk factors, clinical features, and outcomes were assessed. Risk factors entailed the presence of diabetes, chronic renal failure, liver cirrhosis, immunosuppressants, remote infection, underlying malignancy and previous spinal surgery or procedure. We comparatively analyzed the results between the groups of pyogenic and tuberculous spinal infection. SPSS version 14 statistical software was used to perform the analyses of the data. The threshold for statistical significance was established at p<0.05. Results : Ninety-two cases fulfilled the inclusion criteria and were reviewed. Overall, patients of tuberculous spinal infection (TSI) and pyogenic spinal infection (PSI) entailed 20 (21.7%) and 72 (78.3%) cases, respectively. A previous spinal surgery or procedure was the most commonly noted risk factor (39.1%), followed by diabetes (15.2%). The occurrence of both pyogenic and tuberculous spondylitis was predominant in the lumbar spine. Discs are more easily invaded in PSI. At initial presentation, white cell blood count and C-reactive protein levels were higher in PSI compared to TSI (p<0.05). Etiological agents were identified in 53.3%, and the most effective method for identification of etiological agents was tissue culture (50.0%). Staphyococcus aureus was the most commonly isolated infective agent associated with pyogenic spondylitis, followed by E. coli. Surgical treatment was performed in 31.5% of pyogenic spondylitis and in 35.0% of tuberculous spondylitis cases. Conclusion : Many previous studies in Korea usually reported that tuberculous spondylitis is the predominant infection. However, in our study, the number of pyogenic infection was 3 times greater than that of tuberculous spinal disease. Etiological agents were identified in a half of all infectious spinal disease. For better outcomes, we should try to identify the causative microorganism before antibiotic therapy and make every effort to improve the result of culture and biopsy.

Association between ITGB2 Genetic Polymorphisms and Tuberculosis (ITGB2 유전자 다형성과 결핵 사이의 연관성 연구)

  • Jin, Hyun-Seok;Lee, Sang-In;Park, Sangjung
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.2
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    • pp.118-125
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    • 2018
  • Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis (MTB), but the genes associated with the host immune system can be attributed to the development of TB. The ITGB2 gene encodes the integrin beta 2 chain CD18 protein and is present on chromosome 21. The integrin beta 2 chain is an integrin expressed in leukocytes and plays a very important role in leukocyte maturation and attachment. ITGB2 plays an important role in the phagocytosis of MTB and the aggregation of leukocytes in MTB infections. This study examined the genetic polymorphisms of the ITGB2 gene between the TB case and normal control using Korean genomic and epidemiologic data. As a result, a statistically significant correlation was confirmed in 10 SNPs. The most significant SNP was rs113421921 (OR=0.69, CI: 0.53~0.90, $P=5.8{\times}10^{-3}$). In addition, rs173098, one of the significant 10 SNPs, is possibly located in a binding motif with the transcription factor cofactor p300, and can affect ITGB2 gene expression. These findings suggest that the pathogenesis of TB may be influenced by a range of genetic factors related to the immune function of the host, e.g., the reactions associated with the recruitment and attachment of leukocytes. The results of this study could be used to predict the infection control for tuberculosis in a patient-tailored manner.

Bioequivalence Test of Rebamipide 100 mg Tablets (레바미피드 100 mg 정제의 새울학적동등성)

  • Kim, Se-Mi;Cho, Hea-Young;Kang, Hyun-Ah;Lee, Yong-Bok
    • Korean Journal of Clinical Pharmacy
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    • v.18 no.1
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    • pp.38-44
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    • 2008
  • Rebamipide, ($\pm$)-2-(4-chlorobenzoylamino)-3-[2(1H)-quinolinon-4-yl] propionic acid, is used for mucosal protection, healing of gastroduodenal ulcers, and treatment of gastritis. It works by enhancing mucosal defense, scavenging free radicals and temporarily activating genes encoding cyclooxygenase-2. The purpose of the present study was to evaluate the bioequivalence of two rebamipide tablets, $Mucosta^{(R)}$ (Korea Otsuca Pharmaceuticals Co., Ltd.) and Mustar (Korean Drug Co., Ltd.), according to the guidelines of the Korea Food and Drug Administration (KFDA). The release of rebamipide from the two rebamipide formulations in vitro was tested using KP VIII Apparatus II method with pH 6.8 dissolution medium. Twenty six healthy male subjects, $23.46{\pm}2.63$ years in age and $66.62{\pm}8.97\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After a single tablet containing 100 mg as rebamipide was orally administered, blood samples were taken at predetermined time intervals and the concentrations of rebamipide in serum were determined using HPLC with fluorescence detector. The dissolution profiles of two formulations were similar in the tested dissolution medium. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Mucosta^{(R)}$ were -5.08, 3.52 and -9.71 % for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (e.g., log 0.84$\sim$log 1.07 and log 0.90$\sim$log 1.17 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Mustar tablet was bioequivalent to $Mucosta^{(R)}$ tablet.

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A Study on the Biomedical Ethics Consciousness for Euthanasia of the Paramedic Students (응급구조학과 대학생들의 안락사에 대한 생명의료윤리 의식 연구)

  • Choi, Bo-Ram
    • The Korean Journal of Emergency Medical Services
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    • v.14 no.2
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    • pp.41-55
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    • 2010
  • Objective : This study is designed to present the direction and the necessity of education on the biomedical ethics the establish desirable ethical view of paramedic students by understanding on the consciousness of students of department of emergency medical technology on biomedical ethics on euthanasia. Method : Data were collected from on 335 students of department of emergency medical technology in 4-year-college located in districts of Chungcheong-do, from March 4 to April 22, 2010. The questionnaire consisted of total 29 items, i.e., 11 items of general characteristics, 11 items of characteristics related to biomedical ethics and 7 items of consciousness on euthanasia. Result : In general characteristics, the first grade showed the most dense distribution of 37.3%, the second grade was 20.0%, the third grade was 20.9% and the fourth grade was 21.8%. In the consciousness of biomedical ethics on euthanasia, the third and the fourth grades showed a higher ratio(${\chi}^2$ = 136.327, p= .000), in comparison with the first and the second grades, the higher year they were, the higher degree of consciousness they had. The consciousness on each item of euthanasia showed significant differences in grade (F = 8.203, p= .000), experience of clinical practice or none (t = 3.731, p= .000), experience of biomedical ethics education or none (t = 1.997, p = .047) and degree of consciousness on DNR (F = 8.240, p = .000) regarding 'CPR shall not be required in any cases if a patient wants DNR', in experience of biomedical ethics education or none (t = 2.452, p= .015) and degree of consciousness on DNR (F = 2.725, p = .044) regarding if a patient refuses all treatments, the patient's opinion shall be respected', and in degree of consciousness on DNR (F = 2.858, p = . 037) regarding 'after determination of DNR, if the family wants a positive treatment, it shall follow the family's request'. Conclusion : It seemed that the differences in consciousness according to grade and experience of clinical practice were influenced by experiences to treat patients in personally. Moreover, it showed that the higher grade they are, the more experience of education they have, the experiences of education had influences on the consciousness. Development of educational programs is required in order to supply accurate knowledge on biomedical ethics for euthanasia to lower-grade students the to let them establish ethical views properly, and in order to correct wrong knowledge and to establish ethical views while supplying knowledge on biomedical ethics for euthanasia to higher-grade students.

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A Clinical Trial of Dextranase-Containing Mouthwash on the Inhibition of Plaque Formation and Gingivitis (Dextranase 함유 구강 세정액의 치태 억제 및 치은염 예방 효과에 관한 임상적 연구)

  • Song, Woo-Sung;Son, Eun-Ju;Kim, Do-Man;Chung, Hyun-Ju
    • Journal of Periodontal and Implant Science
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    • v.31 no.2
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    • pp.371-388
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    • 2001
  • A novel glucanhydrolase(DXAMase) from a mutant of Lipomyces starkeyi(KSM 22) has been shown effective in hydrolysis of mutan, reduction of mutan formation by Streptococcus mutans and removal pre-formed sucrose-dependentadherent microbial film and DXAMase has been strongly bound to hydroxyapatitie. These in vitro properties of Lipomyces starkeyi DXAMase are desirable for its application as a dental plaque control agent. This study was performed to determine the adjunctive oral hygiene benefits and safety of dextranase(Lipomyces starkeyi KSM 22 DXAMase)-containing mouthwash when used alongside normal tooth-brushing. This 6-month clinical trial was placebo-controlled double-blind design evaluating 1U/ml dextranase mouthwash and 0.12% chlorhexidine mouthwash. A total 39 systemically healthy subjects, who had moderate levels of plaque and gingivitis were included. At baseline, 1, 3 and 6 months, subjects were scored for plaque accumulation(Turesky modification of Quingley-Hein's plaque index), gingivitis status($L\ddot{o}e$ and Silness gingival index), and tooth stain(Area and severity index system by Lang et al). Additionally, oral mucosal examinations were performed and subjects questioned for adverse symptoms. Two weeks after pre-experiment examinations and a professional prophylaxis, the subjects provided with allocated mousewash and instructed to use 20-ml volumes for 30s twice daily after toothbrushing. All the groups showed significant increase in plaque accumulation since 1 month of experiment. During 6 months' period, the Dextranase mouthwash group showed the least increase in plaque accumulation, compared to the Chlorhexidine mouthwash and placebo groups. As for gingival inflammation, all the groups showed significant increase during 6 months of experiment. The Experimental group(Dextranase mouthwash) also showed the least increase in gingival index score, compared to the Positive control(Chlorhexidine mouthwash)as well as the Negative control(placebo)groups. Whereas the tooth stain was increased significantly in the Positive control group, compared to the baseline score and the Negative controlgroup since 3 months of mouthrinsing. It was significantly increased after 6 months in the Experimental group, still less severe than the Positive control group. As for the oral side effect, the Experimental group showed less tongue accumulation, bad taste, compared to the Positive control group. From these results, mouthrinsing with Lipomyces starkeyi KSM 22 dextranase provided adjunctive benefits to toothbrushing, comparable to 0.12% chlorhexidine mouthwash in inhibition of plaque accumulation and gingival inflammation and local side effects were if anything less frequent and less intense than chlorhexidine, with long-term use of the mouthwash. All data had provided positive evidence for Lipomyces starkeyi KSM 22 dextranase as an antiplaque agent and suggested that further development of dextranase formulations for plaque control are warranted.

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Design and Application of Acrylic Electron Wedge to Improve Dose Inhomogeneities at the Junction of Electron Fields (전자선 조사야 결합부분의 선량분포 개선을 위한 Acrylic Electron Wedge의 제작 및 사용)

  • Kim Young Bum;Kwon Young Ho;Whang Woong Ku;Kim You Hyun
    • The Journal of Korean Society for Radiation Therapy
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    • v.10 no.1
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    • pp.60-68
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    • 1998
  • Treatment of a large diseased area with electron often requires the use of two or more adjoining fields. In such cases, not only electron beam divergence and lateral scattering but also fields overlapping and separation may lead to significant dose inhomogeneities(${\pm}20\%$) at the field junction area. In this study, we made Acrylic Electron Wedges to improve dose homogeneities(${\pm}5\%$) in these junction areas and considered application it to clinical practices. All measurements were made using 6, 9, 12, 16, 20MeV Electron beams from a linear accelerator for a $10{\times}10cm$ field at 100cm SSD. Adding a 1 mm sheet of acryl gradually from 1 mm to 15 mm, We acquired central axis depth dose beam profile and isodose curves in water phantom. As a result, for all energies, the practical range was reduced by approximately the same distance as the thickness of the acryl insert, e.g. a 1 mm thick acryl insert reduce the practical range by approximately 1 mm. For every mm thickness of acryl inserted, the beam energy was reduced by approximately 0.2MeV. These effects were almost independent of beam energy and field size. The use of Acrylic Electron Wedges produced a small increase $(less\;than\;3\%)\;in\;the\;surface\;dose\;and\;a\;small\;Increase(less\;than\;1\%)$ in X-ray contamination. For acryl inserts, thickness of 3 mm or greater, the penumbra width increased nearly linear for all energies and isodose curves near the beam edge were nearly parallel with the incident beam direction, and penumbra width was $35\;mm{\sim}40\;mm$. We decide heel thickness and angle of the wedge at this point. These data provide the information necessary to design Acrylic Electron Wedge which can be use to improve dose uniformity at electron field junctions and it will be effectively applicated in clinical practices.

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Surgical Outcomes of Thalamic Tumors in Children: The Importance of Diffusion Tensor Imaging, Neuro-Navigation and Intraoperative Neurophysiological Monitoring

  • Kim, Jun-Hoe;Phi, Ji Hoon;Lee, Ji Yeoun;Kim, Kyung Hyun;Park, Sung-Hye;Choi, Young Hun;Cho, Byung-Kyu;Kim, Seung-Ki
    • Brain Tumor Research and Treatment
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    • v.6 no.2
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    • pp.60-67
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    • 2018
  • Background Recently, modern technology such as diffusion tensor imaging (DTI), neuro-navigation and intraoperative neurophysiological monitoring (IOM) have been actively adopted for the treatment of thalamic tumors. We evaluated surgical outcomes and efficacy of the aforementioned technologies for the treatment of pediatric thalamic tumors. Methods We retrospectively reviewed clinical data from 37 children with thalamic tumors between 2004 and 2017. There were 44 operations (27 tumor resections, 17 biopsies). DTI was employed in 17 cases, neuro-navigation in 23 cases and IOM in 14 cases. All diagnoses were revised according to the 2016 World Health Organization Classification of Tumors of the Central Nervous System. Progression-free survival (PFS) and overall survival (OS) rates were calculated, and relevant prognostic factors were analyzed. The median follow-up duration was 19 months. Results Fifteen cases were gross total resections (GTR), 6 subtotal resections (STR), and 6 partial resections (PR). Neurological status did not worsen after 22 tumor resections. There were statistically significant differences in terms of the extent of resection between the groups with DTI, neuro-navigation and IOM (n=12, GTR or STR=12) and the group without at least one of the three techniques (n= 15, GTR or STR=9, p=0.020). The mean PFS was $87.2{\pm}38.0$ months, and the mean OS $90.7{\pm}36.1$ months. The 5-year PFS was 37%, and the 5-year OS 47%. The histological grade ($p{\leq}0.001$) and adjuvant therapy (done vs. not done, p=0.016) were significantly related to longer PFS. The histological grade (p=0.002) and the extent of removal (GTR/STR vs. PR/biopsy, p=0.047) were significantly related to longer OS. Conclusion Maximal surgical resection was achieved with acceptable morbidity in children with thalamic tumors by employing DTI, neuro-navigation and IOM. Maximal tumor resection was a relevant clinical factor affecting OS; therefore, it should be considered the initial therapeutic option for pediatric thalamic tumors.

Determination of Survival of Gastric Cancer Patients With Distant Lymph Node Metastasis Using Prealbumin Level and Prothrombin Time: Contour Plots Based on Random Survival Forest Algorithm on High-Dimensionality Clinical and Laboratory Datasets

  • Zhang, Cheng;Xie, Minmin;Zhang, Yi;Zhang, Xiaopeng;Feng, Chong;Wu, Zhijun;Feng, Ying;Yang, Yahui;Xu, Hui;Ma, Tai
    • Journal of Gastric Cancer
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    • v.22 no.2
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    • pp.120-134
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    • 2022
  • Purpose: This study aimed to identify prognostic factors for patients with distant lymph node-involved gastric cancer (GC) using a machine learning algorithm, a method that offers considerable advantages and new prospects for high-dimensional biomedical data exploration. Materials and Methods: This study employed 79 features of clinical pathology, laboratory tests, and therapeutic details from 289 GC patients whose distant lymphadenopathy was presented as the first episode of recurrence or metastasis. Outcomes were measured as any-cause death events and survival months after distant lymph node metastasis. A prediction model was built based on possible outcome predictors using a random survival forest algorithm and confirmed by 5×5 nested cross-validation. The effects of single variables were interpreted using partial dependence plots. A contour plot was used to visually represent survival prediction based on 2 predictive features. Results: The median survival time of patients with GC with distant nodal metastasis was 9.2 months. The optimal model incorporated the prealbumin level and the prothrombin time (PT), and yielded a prediction error of 0.353. The inclusion of other variables resulted in poorer model performance. Patients with higher serum prealbumin levels or shorter PTs had a significantly better prognosis. The predicted one-year survival rate was stratified and illustrated as a contour plot based on the combined effect the prealbumin level and the PT. Conclusions: Machine learning is useful for identifying the important determinants of cancer survival using high-dimensional datasets. The prealbumin level and the PT on distant lymph node metastasis are the 2 most crucial factors in predicting the subsequent survival time of advanced GC.

Interactions between NCR+ILC3s and the Microbiome in the Airways Shape Asthma Severity

  • Jongho Ham;Jihyun Kim;Sungmi Choi;Jaehyun Park;Min-gyung Baek;Young-Chan Kim;Kyoung-Hee Sohn;Sang-Heon Cho;Siyoung Yang;Yong-Soo Bae;Doo Hyun Chung;Sungho Won;Hana Yi;Hye Ryun Kang;Hye Young Kim
    • IMMUNE NETWORK
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    • v.21 no.4
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    • pp.25.1-25.16
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    • 2021
  • Asthma is a heterogeneous disease whose development is shaped by a variety of environmental and genetic factors. While several recent studies suggest that microbial dysbiosis in the gut may promote asthma, little is known about the relationship between the recently discovered lung microbiome and asthma. Innate lymphoid cells (ILCs) have also been shown recently to participate in asthma. To investigate the relationship between the lung microbiome, ILCs, and asthma, we recruited 23 healthy controls (HC), 42 patients with non-severe asthma, and 32 patients with severe asthma. Flow cytometry analysis showed severe asthma associated with fewer natural cytotoxicity receptor (NCR)+ILC3s in the lung. Similar changes in other ILC subsets, macrophages, and monocytes were not observed. The asthma patients did not differ from the HC in terms of the alpha and beta-diversity of the lung and gut microbiomes. However, lung function correlated positively with both NCR+ILC3 frequencies and microbial diversity in the lung. Sputum NCR+ILC3 frequencies correlated positively with lung microbiome diversity in the HC, but this relationship was inversed in severe asthma. Together, these data suggest that airway NCR+ILC3s may contribute to a healthy commensal diversity and normal lung function.