• 제목/요약/키워드: Jacob

검색결과 170건 처리시간 0.02초

Common Docking Domain Mutation E322K of the ERK2 Gene is Infrequent in Oral Squamous Cell Carcinomas

  • Valiathan, Gopalakrishnan Mohan;Thenumgal, Siji Jacob;Jayaraman, Bhaskar;Palaniyandi, Arunmozhi;Ramkumar, Hemalatha;Jayakumar, Keerthivasan;Bhaskaran, Sajeev;Ramanathan, Arvind
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제13권12호
    • /
    • pp.6155-6157
    • /
    • 2012
  • Background: Mutations in the MAPK (Mitogen Activated Protein Kinase) signaling pathway - EGFR/Ras/RAF/MEK have been associated with the development of several carcinomas. ERK2, a downstream target of the MAPK pathway and a founding member of the MAPK family is activated by cellular signals emanating at the cell membrane. Activated ERK2 translocates into the nucleus to transactivate genes that promote cell proliferation. MKP - a dual specific phosphatase - interacts with activated ERK2 via the common docking (CD) domain of the later to inactivate (dephosphorylate) and effectively terminate further cell proliferation. A constitutively active form of ERK2 carrying a single point mutation - E322K in its CD domain, was earlier reported by our laboratory. In the present study, we investigated the prevalence of this CD domain E322K mutation in 88 well differentiated OSCC tissue samples. Materials and Method: Genomic DNA specimens isolated from 88 oral squamous cell carcinoma tissue samples were amplified with primers flanking the CD domain of the ERK2 gene. Subsequently, PCR amplicons were gel purified and subjected to direct sequencing to screen for mutations. Results: Direct sequencing of eighty eight OSCC samples identified an E322K CD domain mutation in only one (1.1%) OSCC sample. Conclusions: Our result indicates that mutation in the CD domain of ERK2 is rare in OSCC patients, which suggests the role of genetic alterations in other mitogenic genes in the development of carcinoma in the rest of the patients. Nevertheless, the finding is clinically significant, as the relatively rare prevalence of the E322K mutation in OSCC suggests that ERK2, being a common end point signal in the multi-hierarchical mitogen activated signaling pathway may be explored as a viable drug target in the treatment of OSCC.

Comparison of the Formula of PSA, Age, Prostate Volume and Race Versus PSA Density and the Detection of Primary Malignant Circulating Prostate Cells in Predicting a Positive Initial Prostate Biopsy in Chilean Men with Suspicion of Prostate Cancer

  • Murray, Nigel P;Reyes, Eduardo;Fuentealba, Cynthia;Orellana, Nelson;Morales, Francisca;Jacob, Omar
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제16권13호
    • /
    • pp.5365-5370
    • /
    • 2015
  • Background: Combining risk factors for prostate cancer into a predictive tool may improve the detection of prostate cancer while decreasing the number of benign biopsies. We compare one such tool, age multiplied by prostate volume divided by total serum PSA (PSA-AV) with PSA density and detection of primary malignant circulating prostate cells (CPCs) in a Chilean prostate cancer screening program. The objectives were not only to determine the predictive values of each, but to determine the number of clinically significant cancers that would have been detected or missed. Materials and Methods: A prospective study was conducted of all men undergoing 12 core ultrasound guided prostate biopsy for suspicion of cancer attending the Hospital DIPRECA and Hospital de Carabineros de Chile. Total serum PSA was registered, prostate volumecalculated at the moment of biopsy, and an 8ml blood simple taken immediately before the biopsy procedure. Mononuclear cells were obtained from the blood simple using differential gel centrifugation and CPCs identified using immunocytchemistry with anti-PSA and anti-P504S. Biopsy results were classed as positive or negative for cancer and if positive the Gleason score, number of positive cores and percent infiltration recorded. Results: A total of 664 men participated, of whom 234 (35.2%) had cancer detected. They were older, had higher mean PSA, PSA density and lower PSA-AV. Detection of CPCs had high predictive score, sensitivity, sensibility and positive and negative predictive values, PSA-AV was not significantly different from PSA density in this population. The use of CPC detection avoided more biopsies and missed fewer significant cancers.Conclusions: In this screening population the use of CPC detection predicted the presence of clinically significant prostate cancer better than the other parameters. The high negative predictive value would allow men CPC negative to avoid biopsy but remain in follow up. The formula PSA-AV did not add to the predictive performance using PSA density.

Salivary Her2/neu Levels in Differentiation of Oral Premalignant Disorders and Oral Squamous Cell Carcinomas

  • Varun, Chopra;Dineshkumar, Thayalan;Jayant, VS;Rameshkumar, Annasamy;Rajkumar, Krishnan;Rajashree, Padmanaban;Mathew, Jacob;Arunvignesh, Rajendran K
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제16권14호
    • /
    • pp.5773-5777
    • /
    • 2015
  • Background: Oral squamous cell carcinoma (OSCC) is thought to develop from precancerous dysplastic lesions through multistep processes of carcinogenesis involving activation of oncogenes and loss of tumor suppressor genes. The human epidermal growth factor receptor 2 (Her-2/neu [erbB-2]), a cell membrane glycoprotein, is a growth factor receptor that has receptor tyrosine kinase activity. Her2/neu activation plays a central role in cell proliferation and survival. It has been shown that overexpression of Her2/neu increases the rate of cell division and growth, leading to precancerous changes. The aim of the present study was to compare the serum and salivary Her2/neu levels between cases with premalignant and malignant oral lesions. Materials and Methods: Fasting blood samples and unstimulated saliva by passive drooling were collected from three groups of healthy control (n=20), premalignant disorder (PMD) (n=20) and OSCC (n=25) subjects. The HER2 extracellular domain (HER2 ECD) levels were measured using ELISA. Results: The levels of serum Her2/neu showed no significant differences between any of the groups but on the other hand salivary Her2/neu levels were found to be significantly (p<0.05) higher when compared between control (median 68.7 pg/ml, range: 21.5 - 75.8) and OSCC (median 145.6 pg/ml, range: 45.1-191.1). A similar trend was observed when comparing between PMD (median 43.3, range: 22.1 -94.7) and OSCC with a statistical significance of p<0.05. Conclusions: Our study provided evidence of increased salivary Her2/neu in OSCC when compared to PMD and control which was not the case for serum levels. This suggests that probably Her2/neu is not highly amplified as in breast cancer so as to be reflected in serum. Since saliva is in local vicinity of the OSCC, even a mild increase might be mirrored. On the whole, this study proposes Her2/neu as marker for distinguishing premalignant and malignant conditions.

Evaluation of interleukin-$1{\beta}$ and 8 in gutka chewers with periodontitis among a rural Indian population

  • Jacob, Pulikottil Shaju;Nath, Sonia;Patel, Ritu Prabha
    • Journal of Periodontal and Implant Science
    • /
    • 제44권3호
    • /
    • pp.126-133
    • /
    • 2014
  • Purpose: Smokeless tobacco-based oral-use products like gutka are popular in India. Gutka usage leads to increased periodontal destruction and inflammation; however, the relevant mechanism remains unknown. This study aimed to elucidate the role of gutka in periodontitis by examining its effect on the levels of interleukin (IL) $1{\beta}$ and IL-8 from the gingival crevicular fluid (GCF). Methods: A total of 45 patients were enrolled in this study. Thirty patients with periodontitis (15 gutka chewers [GCP] and 15 nongutka chewers [NGC]) and 15 periodontally healthy controls (HC) were selected. The full-mouth plaque index (PI), gingival index (GI), probing depth (PD), clinical attachment level (CAL), and recession (RC) were recorded. The IL-$1{\beta}$ and IL-8 levels in the GCF of all subjects were assessed through an enzyme-linked immunosorbent assay (Quantikine). Results: The IL-$1{\beta}$ and IL-8 levels were not significantly higher in the GCP group (IL-$1{\beta}$, $369.01{\pm}273.44{\mu}L$; IL-8, $205.97{\pm}196.78{\mu}L$) as compared to those in the NGC group (IL-$1{\beta}$, $195.57{\pm}96.85{\mu}L$; IL-8, $178.61{\pm}149.35{\mu}L$). More gingival RC and loss of attachment was seen among the GCP group (RC: $2.02{\pm}0.31$, P=0.013; CAL: $4.60{\pm}0.56$, P<0.001) than among the NGC group (RC, $1.21{\pm}1.15$; CAL, $3.70{\pm}0.32$); however, PD was deeper among the NGC subjects (P=0.002). PI and GI were significantly higher for the periodontitis group (P<0.001) when compared to the HC, but there was no difference among gutka chewers and non-chewers (P=0.22 and P=0.89). A positive correlation was found between the IL-8 levels and the duration of gutka chewing (r=-0.64, P<0.01). Conclusions: Gutka chewing leads to increased gingival RC and clinical loss of attachment. There was no effect seen in the proinflammatory cytokine levels in the GCF of gutka users.

감정평가에 기반한 환경과 행동패턴 학습을 위한 궤환 모듈라 네트워크 (Learning for Environment and Behavior Pattern Using Recurrent Modular Neural Network Based on Estimated Emotion)

  • 김성주;최우경;김용민;전홍태
    • 한국지능시스템학회논문지
    • /
    • 제14권1호
    • /
    • pp.9-14
    • /
    • 2004
  • 감정은 지능을 지닌 존재의 이성판단에 영향을 준다. 그래서 주변 환경정보에 의해 평가된 기본적이고 보편적인 감정을 로봇에 가미하면 더욱 인간과 가까운 지능 로봇이 될 것이다. 그러나 인간의 감정을 학습하기 위해서는 다양한 감각정보의 학습과 패턴 분류가 선행되어야 하고 이를 위해서 적합한 네트워크 구조가 요구된다. 신경망은 시스템의 특징을 추출하는데 매우 우수한 능력을 발휘하고 있다. 그러나 임시적 혼선현상과 지역 최소치에 수렴하는 단점이 있다. 그래서 복잡한 문제를 단순한 여러 개의 부분적인 문제로 나누어 해결하는 모듈라 설계방법이 관심의 대상이 되고 있다. 본 논문에서는 수많은 감정평가와 학습 데이터 패턴들을 학습하기 위해서 재결합과 재구성에 탁월한 성능을 지닌 Jacobs와 Jordan이 제안한 모듈라 네트워크와 상황의 재 표현이 가능하고 예측값과 모델링에 적합한 특징을 지닌 궤환 신경망을 결합하였다. 구성된 구조는 기존의 모듈라 네트워크의 학습결과와 비교 검토하였다.

Head to Head Comparison of the Chun Nomogram, Percentage Free PSA and Primary Circulating Prostate Cells to Predict the Presence of Prostate Cancer at Repeat Biopsy

  • Murray, Nigel P;Reyes, Eduardo;Orellana, Nelson;Fuentealba, Cynthia;Jacob, Omar
    • Asian Pacific Journal of Cancer Prevention
    • /
    • 제17권6호
    • /
    • pp.2941-2946
    • /
    • 2016
  • Background: The limitations of total serum PSA values remain problematic, especially after an initial negative prostate biopsy. In this prospective study of Chilean men with a continued suspicion of prostate cancer due to a persistently elevated total serum PSA, abnormal digital rectal examination and initial negative prostate biopsy were compared with the use of the on-line Chun nomagram, detection of primary malignant circulating prostate cells (CPCs) and free percent PSA to predict a positive second prostate biopsy. We hypothesized that men negative for circulating prostate cells have a small risk of clinically significant prostate cancer and thus may be conservatively observed. Men positive for circulating prostate cells should undergo biopsy to confirm prostate cancer. Materials and Methods: Consecutive men with a continued suspicion of prostate cancer underwent 12 core TRUS prostate biopsy; age, total serum PSA and percentage free PSA and Chun nomagram scores were registered. Immediately before biopsy an 8ml blood simple was taken to detect primary mCPCs. Mononuclear cells were obtained by differential gel centrifugation and identified using double immunostaining with anti-PSA and anti-P504S. Biopsies were classifed as cancer/no-cancer, mCPC detecton test as negative/positive and the total number of cells/8ml registered. Areas under the curve (AUC) for percentage free PSA, Chun score and CPCs were calculated and compared. Diagnostic yields were calculated with reference to the number of possible biopsies that could be avoided and the number of clinically significant cancers that would be missed. Results: A total of 164 men underwent a second biopsy; 41 (25%) had cancer; the AUCs were 0.65 for free PSA, 0.76 for the Chun score and 0.87 for CPC detection, the last having a significantly superior prediction value (p=0.01). Using cut off values of free PSA <10%, Chun score >50% and ${\geq}1$ CPC detected, CPC detection had a higher diagnostic yield. Some 4/41 cancers complied with the criteria for active surveillance, free PSA and the Chun score missed a higher number of significant cancers when compared with CPC detection. Conclusions: Primary CPC detection outperformed the use of free PSA and the Chun nomagram in predicting clinically significant prostate cancer at repeat prostate biopsy.

Awareness Of Predisposing Factor To Smoking Among Adult In Sokoto

  • John, Ikpeama Osita;Mariam, Onuzulike Nonye;Adimabua, Okafor Patrick;Anthonia, Ikpeama Chizoba;Joy, Ikpeama Chinwe;Osazuwa, Igbineweka Osa;Andrew, Ikpeama Emeka;Jacob, Ofuenyi;Paulastella, Nwosu Nchedochukwu;Nnanna, Ibeh Isaiah;Mokwe, Gerald Chukwudi;Uchechi, Ogwuegbu Juliet;Otugeme, Franklin;Muazu, Mary
    • 식품보건융합연구
    • /
    • 제5권1호
    • /
    • pp.1-11
    • /
    • 2019
  • Smoking has become one of the public health harzard affecting the world. In the UK, smoking is responsible for around one in five deaths. The illnesses caused by smoking extend beyond the well-reported links with cancer, heart disease and respiratory illnesses. Hence the research to determine the awareness of the predisposing factor to smoking among adults in sokoto metropolis. A cross-sectional form of descriptive survey research design was used for this study. This is because descriptive studies are used when the characteristics of a population are either unknown or partially known (Hennekens & Buring, 2007), and it was used by Ganley and Rosario (2013) in a related research this justified the use of similar design in a study of similar nature.Two hundred and seventy returned questionnaire was collected, analyzed using descriptive statistic of frequency count, normative percentage and grand mean; as well as inferential statistics of chi-square (${\chi}^2$). The level of significant was fixed at 0.05. Appropriate degrees of freedom were worked out. There was statistical significant influence or relationship with marital status on the predisposing factors of smoking chi-square of 19716.516 greater than the critical value 43.77297at df 30 p<0.05. There were statistical significance chi-square =27468.348 which is greater than the critical value 43.77297 at df= 30. These show that there is a relationship on gender awareness of predisposing factors to smoking rejecting the null hypotheses. The respondents across different lever/year higher institution shows that the awareness of predisposing factors of smoking there were a statistical significance difference chi-square =7168.429 (df=88) greater than critical value 102.342 rejecting the null hypotheses. There is consistent evidence that links exposure to depictions of smoking in movies and initiation of smoking in young people. Over the years television shows and films have effectively built up associations between smoking and glamour, sex and risk-taking. Social learning theory describes how we learn by example from others. We are strongly influenced by our parents, and other people we look up to, such as peers, actors and pop stars. This can lead us to emulate their behaviour and try smoking.

Extended-spectrum β-lactamase 를 생산하는 Enterobacteriaceae 요로감염에서 카바페넴 이외의 항생제 사용 가능성에 대한 고찰 (Use of Non-carbapenem Antibiotics in Patients with Urinary Tract Infection Caused by Extended-spectrum Beta-lactamase-producing Enterobacteriaceae)

  • 서유빈;김영근;이재갑;송원근
    • 의료관련감염관리
    • /
    • 제21권2호
    • /
    • pp.50-56
    • /
    • 2016
  • ESBL을 생성하는 균주에 의한 요로 감염에서 카바페넴 계열 이외의 항생제를 사용할 수 있는 지를 후향적으로 평가한 연구이다. 만약 in vitro 결과에서 감수성이 있다면 사용이 가능하다는 결과이나 환자의 중증도가 높다면 실패할 수 있음을 강조하였다. 이번 연구 결과를 바탕으로 전향적 연구를 기대해 본다.

Smooth versus Textured Tissue Expanders: Comparison of Outcomes and Complications in 536 Implants

  • Omar Allam;Jacob Dinis;Mariana N. Almeida;Alexandra Junn;Mohammad Ali Mozaffari;Rema Shah;Lauren Chong;Olamide Olawoyin;Sumarth Mehta;Kitae Eric Park;Tomer Avraham;Michael Alperovich
    • Archives of Plastic Surgery
    • /
    • 제51권1호
    • /
    • pp.42-51
    • /
    • 2024
  • Background Increasing concerns regarding the safety of textured surface implants have resulted in surgeons transitioning from textured tissue expanders (TEs) to smooth TEs. Given this change has only recently occurred, this study evaluated outcomes between smooth and textured TEs. Methods Women who underwent two-stage breast reconstruction using TEs from 2013 to 2022 were included. TE-specific variables, perioperative information, pain scores, and complications were collected. Chi-squared, t-test, and linear regression analyses were performed. Results A total of 320 patients received a total of 384 textured and 152 smooth TEs. Note that 216 patients received bilateral reconstruction. TEs were removed in 9 cases. No significant differences existed between groups regarding comorbidities. Smooth TEs had a higher proportion of prepectoral placement (p < 0.001). Smooth TEs had less fills (3±1 vs. 4±2, p < 0.001), shorter expansion periods (60±44 vs. 90±77 days, p < 0.001), smaller expander fill volumes (390±168 vs. 478±177 mL, p < 0.001), and shorter time to exchange (80±43 vs. 104±39 days, p < 0.001). Complication rates between textured and smooth TEs were comparable. Smooth TE had a greater proportion of TE replacements (p = 0.030). On regression analysis, pain scores were more closely associated with age (p = 0.018) and TE texture (p = 0.046). Additional procedures at time of TE exchange (p < 0.001) and textured TE (p = 0.017) led to longer operative times. Conclusion As many surgeons have transitioned away from textured implants, our study shows that smooth TEs have similar outcomes to the textured alternatives.

Utility of Multidetector Computed Tomographic Angiography as an Alternative to Transesophageal Echocardiogram for Preoperative Transcatheter Mitral Valve Repair Planning

  • Craig Basman;Caroline Ong;Tikal Kansara;Zain Kassam;Caleb Wutawunashe;Jennifer Conroy;Arber Kodra;Biana Trost;Priti Mehla;Luigi Pirelli;Jacob Scheinerman;Varinder P Singh;Chad A Kliger
    • Journal of Cardiovascular Imaging
    • /
    • 제31권1호
    • /
    • pp.18-23
    • /
    • 2023
  • BACKGROUND: Three-dimensional (3D) transesophageal echocardiogram (TEE) is the gold standard for the diagnosis of degenerative mitral regurgitation (dMR) and preoperative planning for transcatheter mitral valve repair (TMVr). TEE is an invasive modality requiring anesthesia and esophageal intubation. The severe acute respiratory syndrome coronavirus 2 pandemic has limited the number of elective invasive procedures. Multi-detector computed tomographic angiography (MDCT) provides high-resolution images and 3D reconstructions to assess complex mitral anatomy. We hypothesized that MDCT would reveal similar information to TEE relevant to TMVr, thus deferring the need for a preoperative TEE in certain situations like during a pandemic. METHODS: We retrospectively analyzed data on patients who underwent or were evaluated for TMVr for dMR with preoperative MDCT and TEE between 2017 and 2019. Two TEE and 2 MDCT readers, blinded to patient outcome, analyzed: leaflet pathology (flail, degenerative, mixed), leaflet location, mitral valve area (MVA), flail width/gap, anterior-posterior (AP) and commissural diameters, posterior leaflet length, leaflet thickness, presence of mitral valve cleft and degree of mitral annular calcification (MAC). RESULTS: A total of 22 (out of 87) patients had preoperative MDCT. MDCT correctly identified the leaflet pathology in 77% (17/22), flail leaflet in 91% (10/11), MAC degree in 91% (10/11) and the dysfunctional leaflet location in 95% (21/22) of patients. There were no differences in the measurements for MVA, flail width, commissural or AP diameter, posterior leaflet length, and leaflet thickness. MDCT overestimated the measurements of flail gap. CONCLUSIONS: For preoperative TMVr planning, MDCT provided similar measurements to TEE in our study.