scholarly journals Study of Glutathione-s-transferase and Reduced Glutathione Receiving Chemotherapy

2021 ◽  
pp. 134-140
Author(s):  
Ranjit S. Ambad ◽  
Suryakant Nagtilak ◽  
Rakesh Kumar Jha ◽  
Meghali Kaple
Keyword(s):  
Cervical Cancer ◽  
Locally Advanced ◽  
Three Dimensional ◽  
Figo Stage ◽  
Glutathione S Transferase ◽  
X Ray Crystallography ◽  
Genome Data ◽  
Enzyme Superfamily ◽  
Concentration Changes

Cervical cancer is the third most prevalent cancer in women worldwide, and the fourth leading cause of death from cancer in women. Recent advances, such as the availability of broad scale genome data, articulated gene tag (EST) data bases, innovative sequence alignment techniques, and X-ray crystallography determination of three-dimensional structures, have significantly expanded our understanding of structure–function relationships in this important enzyme superfamily. Total 36 histologically confirmed patients, locally advanced FIGO stage  IIB–IIIB cervical cancer were enrolled. Based on the findings of our research, it can be concluded that improvements in GSH concentration during the treatment of locally advanced cervical cancer can have a major impact on the treatment response. In comparison to the lack of concentration changes in the blood serum of patients who have had no reaction to medication or who have had a reported relapse following treatment, GSH tends to be an effective   indicator.

THREE-DIMENSIONAL PLANNING OF BRACHYTHERAPY FOR LOCALLY ADVANCED CERVICAL CANCER BY CT/MRI IMAGES

2018 ◽  
Vol 64 (5) ◽  
pp. 645-650
Author(s):  
Olga Kravets ◽  
Yelena Romanova ◽  
Oleg Kozlov ◽  
Mikhail Nechushkin ◽  
A. Gavrilova ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Local Control ◽  
Control Volume ◽  
Locally Advanced ◽  
Three Dimensional ◽  
Advanced Cervical Cancer ◽  
3D Ct ◽  
Mri Imaging ◽  
Tumor Target ◽  
Locally Advanced Cervical Cancer

We present our results of 3D CT/MRI brachytherapy (BT) planning in 115 patients with locally advanced cervical cancer T2b-3bN0-1M0. The aim of this study was to assess the differences in the visualization of tumor target volumes and risk organs during the 3D CT/MRI BT. The results of the study revealed that the use of MRI imaging for dosimetric planning of dose distribution for a given volume of a cervical tumor target was the best method of visualization of the soft tissue component of the tumor process in comparison with CT images, it allowed to differentially visualize the cervix and uterine body, directly the tumor volume. Mean D90 HR-CTV for MRI was 32.9 cm3 versus 45.9 cm3 for CT at the time of first BT, p = 0.0002, which is important for local control of the tumor process. The contouring of the organs of risk (bladder and rectum) through MRI images allows for more clearly visualizing the contours, which statistically significantly reduces the dose load for individual dosimetric planning in the D2cc control volume, і.є. the minimum dose of 2 cm3 of the organ of risk: D2cc for the bladder was 24.3 Gy for MRI versus 34.8 Gy on CT (p = 0.045); D2cc for the rectum - 18.7 Gy for MRI versus 26.8 Gy for CT (p = 0.046). This is a prognostically important stage in promising local control, which allows preventing manifestation of radiation damage.

Three-dimensional dose accumulation in pseudo-split-field IMRT and brachytherapy for locally advanced cervical cancer

Brachytherapy ◽  
2015 ◽  
Vol 14 (4) ◽  
pp. 481-489 ◽  
Author(s):  
Baozhou Sun ◽  
Deshan Yang ◽  
Jackie Esthappan ◽  
Jose Garcia-Ramirez ◽  
Samantha Price ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Locally Advanced ◽  
Three Dimensional ◽  
Advanced Cervical Cancer ◽  
Dose Accumulation ◽  
Locally Advanced Cervical Cancer ◽  
Split Field

scholarly journals Role of Computational Methods in Going beyond X-ray Crystallography to Explore Protein Structure and Dynamics

2018 ◽  
Vol 19 (11) ◽  
pp. 3401 ◽  
Author(s):  
Ashutosh Srivastava ◽  
Tetsuro Nagai ◽  
Arpita Srivastava ◽  
Osamu Miyashita ◽  
Florence Tama
Keyword(s):  
Protein Dynamics ◽  
Computational Methods ◽  
Protein Structures ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
X Ray ◽  
X Ray Crystallography ◽  
Insight Into

Protein structural biology came a long way since the determination of the first three-dimensional structure of myoglobin about six decades ago. Across this period, X-ray crystallography was the most important experimental method for gaining atomic-resolution insight into protein structures. However, as the role of dynamics gained importance in the function of proteins, the limitations of X-ray crystallography in not being able to capture dynamics came to the forefront. Computational methods proved to be immensely successful in understanding protein dynamics in solution, and they continue to improve in terms of both the scale and the types of systems that can be studied. In this review, we briefly discuss the limitations of X-ray crystallography in studying protein dynamics, and then provide an overview of different computational methods that are instrumental in understanding the dynamics of proteins and biomacromolecular complexes.

Three-Dimensional Transvaginal Ultrasonography for Locally Advanced Cervical Cancer

2013 ◽  
Vol 23 (8) ◽  
pp. 1459-1464 ◽  
Author(s):  
Jung Mi Byun ◽  
Young Nam Kim ◽  
Dae Hoon Jeong ◽  
Ki Tae Kim ◽  
Moon Su Sung ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Locally Advanced ◽  
Three Dimensional ◽  
Transvaginal Ultrasonography ◽  
Advanced Cervical Cancer ◽  
Locally Advanced Cervical Cancer

scholarly journals Postoperative Adjuvant Chemotherapy in Locally Advanced Cervical Cancer Patients with Optimal Response to Neoadjuvant Chemotherapy: A Retrospective Study

2020 ◽  
Author(s):  
Xiaojie Feng ◽  
Hongmin Chen ◽  
Lei Li ◽  
Ling Gao ◽  
Xupeng Bai ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Adjuvant Chemotherapy ◽  
Locally Advanced ◽  
Disease Free Survival ◽  
Figo Stage ◽  
Optimal Number ◽  
Chinese Patients ◽  
Optimal Response ◽  
Increased Risk ◽  
Significant Difference

Abstract Background. Few studies investigated the effectiveness of adjuvant chemotherapy (CT) in patients with optimal response to neoadjuvant CT (NACT), and an optimal number of treatment cycles for these patients remains unknown. Methods. A total of 261 Chinese patients with FIGO stage Ib2–IIb cervical cancer who showed an optimal response to NACT were included after radical surgery (RS), and the disease-free survival (DFS) and overall survival (OS) of patients treated with different cycles of postoperative adjuvant CT were compared. Results. We found that patients treated with different cycles of postoperative adjuvant CT were significantly better than those without further therapy. The multivariate analysis showed that postoperative adjuvant CT was an independent prognostic factor for DFS. However, there was no significant difference in the DFS and OS between patients who had 3 cycles of adjuvant CT and those with 6 cycles. Further analysis revealed a significant association of 6 cycles of adjuvant CT with increased risk of leukopenia, nausea/vomiting, and rash. Conclusion. These data suggest that additional 3 cycles of adjuvant CT after NACT + RS may improve the clinical outcome of optimal responders in terms of DFS, OS, and drug toxicity.

Structural Analysis of Proteins on Lipid Substrates

2000 ◽  
Vol 6 (S2) ◽  
pp. 1182-1183
Author(s):  
Elizabeth M. Wilson-Kubalek
Keyword(s):  
Structural Information ◽  
Rapid Determination ◽  
3D Structure ◽  
Three Dimensional ◽  
Molecular Complexes ◽  
Structural Data ◽  
X Ray Crystallography ◽  
Helical Protein ◽  
3D Structure Determination

Electron microscopy (EM) has become an increasingly powerful method for the determination of three-dimensional (3D) structures of proteins and macromolecular complexes. EM offers advantages over X-ray crystallography and NMR for obtaining structural information about proteins in physiological conditions, as components of large assemblies, that cannot be obtained in large quantity, or that fail to yield 3D crystals. EM has been used to obtain structural data from images of isolated molecules and molecular complexes, two-dimensional (2D) protein crystals, and helical protein arrays. Helically arranged proteins allow the most rapid determination of 3D maps because they contain a complete range of equally spaced molecular views, therefore no tilting of the sample with respect to the electron beam is required. However, so far 3D structure determination of helical assemblies has been limited to proteins that naturally adopt this organization and to proteins that fortuitously crystallize as helices.

A new marker based on risk stratification of human papillomavirus DNA and tumor size to predict survival of locally advanced cervical cancer

2019 ◽  
Vol 29 (3) ◽  
pp. 459-465 ◽  
Author(s):  
Yecai Huang ◽  
Qiao He ◽  
Ke Xu ◽  
Jie Zhou ◽  
Jun Yin ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Overall Survival ◽  
Risk Stratification ◽  
Tumor Size ◽  
Locally Advanced ◽  
Figo Stage ◽  
Advanced Cervical Cancer ◽  
Hpv Dna ◽  
Locally Advanced Cervical Cancer ◽  
Advanced Cervical Carcinoma

ObjectiveTo assess the prognostic value of human papillomavirus (HPV) viral load in locally advanced cervical carcinoma treated with radical concurrent chemoradiotherapy.MethodsFrom January 2012 to October 2013, a total of 246 locally advanced cervical carcinoma patients were included in this retrospective study. HPV DNA status was tested by Hybrid Capture 2 assay. Tumor size was measured on T2WI. All the patients in the study received concurrent cisplatin-based chemoradiotherapy with intensity-modulated radiotherapy and three-dimensional brachytherapy. Survival rate was calculated by the Kaplan-Meier method, and a log-rank test was used to compare the survival. Multivariate analysis employed the Cox regression model.ResultsThe median follow-up time was 52 months. The median value of HPV DNA was 163.13 relative light unit/cut-off (RLU/CO) (range 1.65–2162.62 RLU/CO). The 5-year overall survival, distant metastasis-free survival of patients in the low HPV DNA group (HPV DNA ≤ 163.13 RLU/CO) and the high HPV DNA group (HPV DNA > 163.13 RLU/CO) were 46.3 % vs 58.5 % (p = 0.009) and 65.9 % vs 75.6% (p = 0.003), respectively. Multivariate analysis showed that the HPV DNA, tumor size, and International Federation of Gynecology and Obstetrics (FIGO) stage were independent prognostic factors for overall survival and distant metastasis-free survival. We choose the tumor size and HPV DNA as the risk stratification factors to build a new prediction marker which can better predict overall survival for locally advanced cervical cancer than can the FIGO stage.ConclusionsHPV DNA may be a useful biomarker for locally advanced cervical cancer. Low HPV load predicts a worse survival. The new marker based on risk stratification by combining HPV DNA and tumor size is better associated with overall survival of locally advanced cervical cancer treated with concurrent chemoradiotherapy.

CALLA: Efficacy and safety of durvalumab with and following concurrent chemoradiotherapy (CCRT) versus CCRT alone in women with locally advanced cervical cancer: A phase III, randomized, double-blind, multicenter study.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS5597-TPS5597 ◽  
Author(s):  
Bradley J. Monk ◽  
Jyoti Mayadev ◽  
Ana T Nunes ◽  
Alicja Dabrowska Brown ◽  
Michelle Marcovitz ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Locally Advanced ◽  
Figo Stage ◽  
Stage Iii ◽  
Disease Stage ◽  
Advanced Cervical Cancer ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Locally Advanced Cervical Cancer ◽  
Eortc Qlq

TPS5597 Background: CCRT is the standard of care for locally advanced cervical cancer. CCRT with PD-1/PD-L1 pathway blockade may promote a more immunogenic environment through increased phagocytosis, cell death, and antigen presentation, leading to enhanced immune-mediated tumor surveillance. This Phase 3, randomized, multicenter, international, double-blind, placebo-controlled study is designed to determine the efficacy and safety of durvalumab with and following CCRT vs. CCRT alone in women with locally advanced cervical cancer (NCT03830866). Methods: The study will enroll immunotherapy-naïve adult patients (pts) with histologically confirmed cervical adenocarcinoma or cervical squamous or adenosquamous carcinoma (FIGO Stages IB2-IIB with node [N] positive and IIIA-IVA with any N) and no prior definitive surgical, radiation, or systemic therapy for cervical cancer. Approximately 714 pts will be randomized 1:1 to receive either durvalumab (1500 mg intravenously [IV]) or placebo every 4 weeks for 96 weeks. All pts will receive CCRT to the pelvis or pelvis + para-aortic radiotherapy field (45 Gy), followed by image-guided brachytherapy with cisplatin (40 mg/m2) IV or carboplatin (AUC2) IV once weekly for 5 weeks (6th dose optional). Randomization will be stratified by disease stage (FIGO Stage < III and N positive, FIGO Stage ≥III and N negative, or FIGO Stage ≥III and N positive) and region (US, Canada, EU, South Korea, and Japan vs. rest of the world). The primary endpoint is progression-free survival (assessed by investigator per RECIST v1.1 or histopathologic confirmation of local tumor progression). Secondary endpoints are overall survival, objective response and complete response (CR) rates, duration of response in pts with CR, incidence of local or distant disease progression or secondary malignancy, disease-related symptoms, and health-related quality of life (EORTC QLQ-C30 and EORTC QLQ-CX24). Pharmacokinetics, immunogenicity, and safety of durvalumab will also be assessed. Pt enrollment is ongoing. Clinical trial information: NCT03830866.

A STUDY ON THE NEOADJUVANT CHEMOTHERAPY WITH CHEMORADIATION VERSUS DEFINITIVE CHEMORADIATION IN LOCALLY ADVANCED STAGE OF CERVICAL CANCER

2021 ◽  
pp. 67-69
Author(s):  
Subhas Haldar ◽  
Archana Dixit ◽  
Dinesh Kumar Saroj ◽  
Debarshi Jana
Keyword(s):  
Cervical Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Response Rate ◽  
Locally Advanced ◽  
Figo Stage ◽  
Cancer Center ◽  
Open Label ◽  
Randomized Control ◽  
Control Study ◽  
Better Than

Introduction: Ajoint study on cervical cancer prepared by ASSOCHAM-National Institute of Cancer Prevention and Research (NICPR) reveals, India alone accounts for one-fourth of global burden of cervical cancers. To compare the response rate in neoadjuvant chemotherapy arm versus only denitive chemoradiation for cervical stage IIB to IVApatients. Materials and methods: The study involves accrual of patients at the Department of Radiotherapy, Saroj Gupta Cancer center and research institute. Allocation: Prospective, parallel, open label, single institutional randomized control study. Conclusion: We concluded that the response rate in neoadjuvant chemotherapy arm was better than only denitive chemoradiation for cervical FIGO stage IIB to IVApatient

Structure of complement receptor (CR) 2 and CR2-C3d complexes

2002 ◽  
Vol 30 (6) ◽  
pp. 983-987 ◽  
Author(s):  
J. Hannan ◽  
K. Young ◽  
G. Szakonyi ◽  
M. J. Overduin ◽  
S. J. Perkins ◽  
...  
Keyword(s):  
Three Dimensional ◽  
Glycosylation Site ◽  
Dimensional Structure ◽  
Complement Receptor ◽  
Ligand Interaction ◽  
X Ray Crystallography ◽  
Short Consensus Repeats ◽  
Autoimmune Mouse ◽  
Crystal Complex

Using X-ray crystallography, we have determined the structure of the first two short consensus repeats (SCRs) of human complement receptor (CR) 2 in complex with C3d. These studies revealed: (i) a primary site of interaction for C3d within SCR2 of CR2, (ii) a hydrophobic patch holding SCR1 to SCR2 in a rigid V-shape, (iii) a dimer formed by interactions between SCR1 of each molecule, (iv) several non-linear sequences on C3d that interact with CR2 and (v) mutations of C3d amino acids within the co-crystal interface that resulted in decreased binding. In addition, a polymorphism that results in decreased C3d binding and introduces a new glycosylation site predicted to disrupt the dimer interface was found in the New Zealand White autoimmune mouse strain. Although the co-crystal complex results are in agreement with a subset of prior studies, our additional findings, which demonstrate an extended SCR1-SCR2 structure in solution and differences in the kinetics of ligand-receptor interactions with longer forms of CR2, have suggested a more complex receptor-ligand interaction. To characterize this interaction further, several approaches directed at the determination of solution phase interactions as well as the analysis of the three-dimensional structure of CR2 alone and key CR2 mutants will be necessary.

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