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Background and objective
To determine changes in reduced glutathione (GSH) and glutathione S-transferase (GST) during neoadjuvant chemotherapy followed by concurrent chemoradiation for patients with stage IIB–IIIB cervical cancer, and to evaluate their significance to the efficacy of the treatment.
Materials and methods
According to the prospectiv...
Contexts in source publication
Context 1
... patients were grouped according to the FIGO stage of the disease, the GSH concentration after NACT increased significantly in both IIB and IIIB stages. After chemoradiation, values of this rate decreased in contrast with GSH concentra- tion after NACT only in the case of stage IIB (Table 3). Statistically significant changes in GST concentration of stage IIB and stage IIIB cervical cancer were not identified during the treatment. ...
Context 2
... order to assess changes in GSH and GST concentrations according to the response to treatment by NACT based on a combination of cisplatin and gemcitabine, patients were divided into 2 groups: one of them (n = 26) had a positive (all of the patients partial) response to the treatment, while the other group (n = 10) had no response (stable disease). It has to be noted that, given the positive response toward the treatment, GSH concentrations showed a significant increase after NACT , 210 211 212 213 214 215 216 217 218 219 220 221 222 223 224 225 226 227 228 229 230 231 232 233 234 235 236 237 238 239 240 241 242 243 244 245 246 247 248 249 250 251 252 253 254 255 256 Table 4 -GST and GSH changes during treatment according to regional lymph nodes metastases, defined by using radiological methods. Values are mean AE standard deviation. ...
Context 3
... results revealed that the levels of GSH and GSH-Px in patients with cervical cancer were significantly lower than those of the control group. This study also demonstrated the effect of radiation therapy on the antioxi- dant system, but a relationship between GSH, GSH- Px changes 257 258 259 260 261 262 263 264 265 266 267 268 269 270 271 272 273 274 275 276 277 278 279 280 281 282 283 284 285 286 287 288 289 290 291 292 293 294 295 296 297 298 299 300 301 302 303 304 305 306 307 Table 7 -GST and GSH changes in the blood, after the treatment of cervical cancer according to the disease progression during the first 2 years after the treatment. Values are mean AE standard deviation. ...
Context 4
... the treatment, the level of plasma lipid peroxide was higher, while the level of endogenous antiox- idants and antioxidant enzymes, including GSH and GST, was lower, in contrast with levels of lipid peroxide and antiox- idants and antioxidant enzymes in the control group. After chemotherapy, the level of lipid peroxide decreased signifi- cantly in patients who had CR prior to treatment, in contrast 308 309 310 311 312 313 314 315 316 317 318 319 320 321 322 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401 402 403 404 405 406 407 408 409 410 411 412 413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 with those who had PR or no response at all. These differences remained significant after the treatment and during the follow-up period. ...
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... after the treatment, in contrast with the absence of concentration changes in the blood serum of patients with no response to the treatment or ones with an established relapse after the treatment, points to GSH as an important predictive factor. Statistically significant changes in GST concentration levels during the treatment were not observed . 478 479 480 481 482 483 484 485 486 487 488 489 490 491 492 493 494 495 496 497 498 499 500 501 502 503 504 505 506 507 508 509 510 511 512 513 514 515 516 517 518 519 520 521 522 523 524 525 526 527 528 529 530 531 532 533 534 535 536 537 538 539 540 541 542 543 544 545 546 547 548 549 550 551 552 553 554 555 556 557 558 559 560 561 562 563 564 565 566 567 568 569 570 m e d i c i n a x x x ( 2 0 1 4 ) x x x -x x ...
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Simple Summary
Amino acid metabolism is aberrantly altered in pancreatic cancer (PC). Evidence suggests that circulating histidine (His) levels are low in PC. However, the role of His in modulating the progression of PC remains unknown. We determined the role of His in altering the therapeutic effectiveness of gemcitabine (Gem) against PC. We provi...
Citations
... There is also evidence that glutathione levels are increased by radiation in the context of cancer. 57,214 In addition to glutamate, glutathione is made from cysteine and glycine, the latter of which can either be imported or synthesized from serine. While cells can take up free serine from their environment or synthesize it de novo from glucose, some cancer subtypes become addicted to de novo production of serine. ...
Tumor metabolism has emerged as a hallmark of cancer and is involved in carcinogenesis and tumor growth. Reprogramming of tumor metabolism is necessary for cancer cells to sustain high proliferation rates and enhanced demands for nutrients. Recent studies suggest that metabolic plasticity in cancer cells can decrease the efficacy of anticancer therapies by enhancing antioxidant defenses and DNA repair mechanisms. Studying radiation-induced metabolic changes will lead to a better understanding of radiation response mechanisms as well as the identification of new therapeutic targets, but there are few robust studies characterizing the metabolic changes induced by radiation therapy in cancer. In this review, we will highlight studies that provide information on the metabolic changes induced by radiation and oxidative stress in cancer cells and the associated underlying mechanisms.
... The lack of polymorphic variants in the genes GSTT1, GSTM1, and GSTP1 can reduce the functional activity of glutathione enzymes and increase the clinical severity of many diseases, including cancer [85]. A study showed an increase in the concentration of GSH after chemotherapy in cervical cancer patients, which may be vital for predicting the efficacy of the treatment [86]. Abbas et al. [87] reported that patients with GSTM1 in combination with TT1-null and TP1 (AG + GG) had a higher survival benefit for cervical cancer [87]. ...
Numerous studies have provided novel insights into the potential role of genetic polymorphisms as prognostic markers in gynecologic cancers, particularly cervical cancer. Cervical cancer is the second most common and primary cause of cancer-related deaths in developing countries. Deep research into single-nucleotide polymorphisms (SNPs) may help to explain potential differences in distinct cancers. Candidate SNPs may be involved in immune cell regulation, cell-cycle control, DNA damage and repair, cancer metabolism, and apoptosis. In the present chapter, we have summarized important findings of genetic association studies exploring the role of glutathione-S-transferase (GST), interleukins (ILs), p53 codon 72, tumor necrosis factor A gene (TNFA), human leukocyte antigen (HLA), Fas gene polymorphism, murine double-minute two homologs (MDM2), and interferons-γ (IFNG) gene polymorphism with cervical cancer. Genetic association studies will require further validation to provide direction for future research leading to better clinical outcomes for patients with cervical cancer.
... Moreover, reduced GSH levels are associated with patient's response to treatment. 94 Predictive role of GSH for patients with CC undergoing chemoradiotherapy is also shown by Daukantienė et al and Vidyasagar et al. 95,96 Srivastava et al demonstrated that increased lipid peroxidation and reduced levels of GSH, SOD, Vitamin A, and E in patients with CC are significantly associated with tumor stage, suggesting their clinical significance as prognostic markers. 97 In contrast, Sharma et al reported higher levels of GSH in patients with CC following chemotherapy. ...
Cervical cancer (CC) is one of the most common cancers among females, and it is most notable in developing countries. The exact etiology of CC is poorly understood; but, smoking, oral contraceptives, immunosuppression, and infection with human papillomavirus (HPV) may increase the risk of CC. There is also an association between CC and oxidative stress. Oxidative stress is caused by a disturbed oxidant‐antioxidant balance in favor of the former, leading to an excessive generation of free radicals, particularly reactive oxygen species (ROS), and subsequently to biological damages. Thus, redox enzymatic and nonenzymatic regulators are required to maintain the redox homeostasis. Dysregulated antioxidants system and the pathogenic role of oxidative stress in CC have been investigated in several clinical and preclinical studies. In this study, we reviewed studies that have addressed the cross‐talk between oxidative stress and CC pathogenesis and resistance to therapy. In this review, we attempted to give an overview of recent preclinical and clinical studies that have addressed the possible role of oxidative stress in cervical cancer (CC) pathogenesis and chemo/radioresistance. We also summarized the potential use of oxidative stress as a diagnostic or prognostic biomarker.
... GSTP1, GSTM1, and GSTT1 are three members of the human glutathione S-transferases (GSTs) super family of genes, and they are polymorphic in humans. Previous studies have reported that GST polymorphisms can influence the effectiveness of the detoxification of cytotoxins generated by cisplatin-based chemotherapy in several kinds of cancer, including osteosarcoma, cervical cancer, and gastric cancer (Daukantienė et al., 2014;Yu et al., 2014;Goričar et al., 2015). The authors of several studies have investigated the relationship between GST polymorphisms and the prognosis of NSCLC, but the results are inconsistent. ...
We analyzed the association between polymorphisms in three glutathione S-transferase genes (GSTP1, GSTM1, and GSTT1) and the treatment outcome for advanced non-small cell lung cancer (NSCLC). We recruited 284 NSCLC patients at advanced stage from Department of Radiotherapy in Peace Hospital Attached to Changzhi Medical College between May 2009 and May 2011, who had received cisplatin-based chemotherapy. The GSTP1, GSTM1, and GSTT1 genotyping for was determined using DNA pyrosequencing on an ABI Prism 3100 DNA analyzer. In the Cox proportional hazards model, the IIe/Val and Val/Val genotypes of GSTP1 were associated with lower risk of disease progression compared with the IIe/IIe genotype, and the HRs (95%CIs) were 0.37 (0.18-0.74) and 0.15 (0.06-0.35), respectively. The IIe/Val and Val/Val genotypes significantly decreased risk of death from all causes in patients with NSCLC, and the HRs (95%CIs) were 0.52 (0.29-0.92) and 0.37 (0.17-0.79), respectively No significant association was observed between GSTM1 and GSTT1 polymorphisms and progression-free survival and overall survival in the NSCLC patients. In summary, we suggest that GSTP1 polymorphisms might influence the treatment outcome of advanced NSCLC patients, and our results could help improve individualized therapy.
... Therefore, polymorphisms in the GSTM1, GSTT1, and GSTP1 genes could alter the metabolism of chemotherapeutic drugs and modify the effectiveness of therapy. Previous studies have reported that GSTs polymorphisms could influence the effectiveness of detoxifying cytotoxins generated by cisplatin-based chemotherapy in several kinds of cancers, including osteosarcoma, cervical cancer and gastric cancer [9][10][11]. Previous studies reported the GSTs polymorphisms and prognosis of NSCLC, but the results are in consistent [12][13][14][15]. ...
This study aimed to investigate the possible association between GSTP1, GSTM1, and GSTT1 polymorphisms and treatment outcome of advanced NSCLC. Between October 2009 and October 2011, a total of 308 patients of NSCLC on stage IIIA, IIIB or IV, treated with cisplatin-based chemotherapy were included. Polymerase chain reaction-restriction fragment length polymorphism was used to genotype the GSTP1 and GSTM1, and GSTT1 polymorphisms. We found that the IIe/Val and Val/Val genotypes of GSTP1 showed more CR+PR to chemotherapy in advanced NSCLC when compared with IIe/IIe genotype, and the Ors (95% CI) were 0.37 (0.18-0.71) and 0.15 (0.07-0.38). The IIe/Val and Val/Val genotypes of GSTP1 were associated with longer overall survival of advanced NSCLC when compared with the IIe/IIe genotype (For IIe/Val vs IIe/IIe, 37.63 ± 2.01 months vs 30.25 ± 2.06 months; for Val/Val vs IIe/IIe, 39.84 ± 3.36 months vs 30.25 ± 2.06 months). In the Cox proportional hazards model, the IIe/Val and Val/Val genotypes significantly decreased risk of death from all causes in patients with advanced NSCLC, and the HRs (95% CIs) were 0.51 (0.28-0.94) and 0.35 (0.16-0.78), respectively. We found that the GSTP1 polymorphisms might affect the clinical outcome of patients with advanced NSCLC, and our results could help us to facilitate therapeutic decision for individualized therapy.
Gynecologic cancers are the leading causes of cancer-related deaths among women. In recent years, advances in the understanding of gynecologic cancers and their therapeutic
strategies have been encouraging. Patients with gynecologic malignancies often develop
resistance to the currently used chemotherapy. Overcoming resistance to such therapies
poses a decisive challenge in the management of patients with gynecologic cancer that impacts their survival and quality-of-life. The patients who belong to certain ethnicity/race
possess differences in developing resistance and exhibit disparities in reacting to the therapy(ies). In this volume, eminent researchers / clinicians from across the globe
contributed various chapters covering important topics related to drug resistance, reversing the drug resistance, and associated mechanisms / targets in major gynecologic
cancers (i.e., cervical, endometrial, and ovarian cancers). The contributors stipulated consolidated information on these gynecologic cancers and response rates, lifestyle changes, health disparities, genetic polymorphism, and nanotechnology for addressing drug resistance. This volume provides up-to-date information with a broader scope summarized in the same volume for students, researchers, trainees, and clinicians who are interested in the study of gynecologic cancers, covering basic, translational, and applied clinical aspects in reversing the drug resistance. These topics are unique to this volume, which are not generally covered in other peer-reviewed publications, thus representing a valuable scholarly resource for scientists and clinicians across the globe.
Tumor cells may develop multidrug resistance (MDR) to various chemotherapy regimens. Such resistance reduces the sensitivity of cells to chemotherapy drugs, leading to the failure of cervical cancer (CC) treatment and disease progression. The present study aimed to investigate the role of MDR1, lung resistance protein (LRP) and placental glutathione S‑transferase π 1 (GSTP1) in CC and MDR, and the prognostic value of these genes. The mRNA expression levels of these resistance‑associated genes were determined in 47 CC and 20 healthy cervical tissue samples. Subsequently, the data was analyzed alongside clinicopathological parameters. The mRNA expression levels of MDR1, LRP and GSTP1 in CC were 0.57±0.32, 0.58±0.29 and 0.44±0.24, respectively, whereas those in healthy cervical tissues were 0.19±0.10, 0.17±0.14 and 0.18±0.10, respectively. Therefore, the expression levels of these genes were significantly greater in CC compared with healthy cervical tissue (P<0.05). mRNA expression levels of MRD1 were increased in the well differentiated group (0.68±0.27) compared with the poorly differentiated group (0.38±0.33; P<0.05). No significant differences were observed between LRP and GSTP1 mRNA expression levels and tumor differentiation or clinical stage of the patients (P>0.05). Multivariate logistic regression indicated that the degree of differentiation and the MDR1 gene expression levels were predictors of CC prognosis (P<0.05). The survival rate of patients in the MDR1‑negative group was significantly greater compared with the MDR1‑positive group (P<0.05). The results of the present study therefore suggested that MDR1 gene expression is a predictor of poor survival in CC.
The combination of organic and inorganic materials to create hybrid nanostructures is an effective approach to develop label-free platforms for biosensing as well as to overcome eventual leakage current-related problems in capacitive sensors operating in liquid. In this work, we combine an ultra-thin high-k dielectric layer (Al2O3) with a nanostructured organic functional tail to create a platform capable of monitoring biospecific interactions directly in liquid at very low analyte concentrations. As a proof of concept, a reversible label-free glutathione-S-transferase (GST) biosensor is demonstrated. The sensor can quantify the GST enzyme concentration through its biospecific interaction with tripeptide reduced glutathione (GSH) bioreceptor directly immobilized on the dielectric surface. The enzymatic reaction is monitored by electrical impedance measurements, evaluating variations on the overall capacitance values according to the GST concentration. The biosensor surface can be easily regenerated, allowing the detection of GST with the very same device. The biosensor shows a linear response in the range of 200 pmol.L⁻¹ to 2 µmol.L⁻¹, the largest reported in the literature along with the lowest detectable GST concentration (200 pmol.L⁻¹) for GST label-free sensors. Such a nanostructured hybrid organic-inorganic system represents a powerful tool for the monitoring of biochemical reactions, such as protein-protein interactions, for biosensing and biotechnological applications.
