scholarly journals Variability of glutathione S-transferase isoenzyme patterns in matched normal and cancer human breast tissue

1994 ◽  
Vol 304 (3) ◽  
pp. 843-848 ◽  
Author(s):  
M K Kelley ◽  
A Engqvist-Goldstein ◽  
J A Montali ◽  
J B Wheatley ◽  
D E Schmidt ◽  
...  

The determination of GST levels in blood has been proposed to a marker of tumour burden in general, whereas level of the P1 isoenzyme has been identified as a prognostic factor for breast-cancer patients receiving no adjuvant chemotherapy. Particular glutathione S-transferase (GST) isoenzymes differ in their substrate specificity, however, and their presence or absence might therefore account for the resistance of tumours to particular chemotherapeutic drugs, as already established for cultured cell lines. Determination of the GST isoenzyme profile of a cancer tissue could have prognostic value in the selection of treatment if the levels of expression/activity show a degree of variation comparable with that exhibited by actual patient responses. Using reversed-phase h.p.l.c. to quantify affinity-isolated GSTs, we have analysed full isoenzyme profiles in the first large sample of matched normal and cancer human tissues (18 breast-cancer patients). In no patients did the tumour tissues express any isoenzymes that were not found in normal breast tissue. In addition to the GSTs, another enzyme, identified as enoyl-CoA isomerase, was regularly found in breast tissue cytosol following elution from a hexyl-glutathione affinity column. In most cases, the average level of GST was substantially elevated in the cancer tissues above the levels in normal breast tissue from the same patient. Furthermore, the relative levels of the isoenzymes were substantially more variable in the cancer samples than in the normal breast tissue, providing a plausible mechanism for the well established variable response to treatment.

2002 ◽  
Vol 76 (2) ◽  
pp. 125-130 ◽  
Author(s):  
Elvio G. Silva ◽  
Dinu Mistry ◽  
Donghui Li ◽  
Henry M. Kuerer ◽  
Edward N. Atkinson ◽  
...  

1986 ◽  
Vol 1 (1) ◽  
pp. 33-38 ◽  
Author(s):  
Massimo Gion ◽  
Riccardo Mione ◽  
Ruggero Dittadi ◽  
Luciano Griggio ◽  
Gabriele Munegato ◽  
...  

The study of tumor markers in breast cancer tissue may supply information on the tumor's biological features and its clinical behaviour. Forty-nine primary breast cancer patients are evaluable to date. CEA, ferritin, TPA and CA15/3 were measured with radioimmu-nometric methods in the cytosol of carcinoma and normal tissue from the same breast. The concentrations of the four markers were higher in the tumor than in normal tissue in 42/49 cases for CEA, 47/49 for ferritin, 42/49 for TPA and in 24/29 for CA15/3. However, an overlap was found between carcinoma and normal tissue levels, particularly for CEA and TPA. We can conclude that the four substances studied may be markers of malignancy in breast carcinoma when nonmalignant breast tissue from the same patient is determined at the same time, whereas assays within a single, unknown breast tissue sample may be useful only in the case of ferritin and, partly, CA15/3.


2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Erin W. Hofstatter ◽  
Steve Horvath ◽  
Disha Dalela ◽  
Piyush Gupta ◽  
Anees B. Chagpar ◽  
...  

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22172-e22172
Author(s):  
M. Seker ◽  
F. Y. Erkal ◽  
A. Bilici ◽  
T. Salman ◽  
B. O. Ustaalioglu ◽  
...  

e22172 Background: Adiponectin is a novel adipocyte-secreted proteine and associated with insulin-resistant (IR) status, such as type 2 diabetes mellitus and obesity. The inverse correlation between serum adiponectin levels and breast cancer risk was previously documented. Moreover, the association of high tissue adiponectin levels with breast cancer has been recently reported. In the present study, the relationship among tumor, normal breast tissue and serum adiponectin levels, breast cancer, and the other IR parameters were evaluated. Methods: Fifty-three patients with diagnosed and histologically confirmed breast cancer were included in our study. We analyzed the correlation among the levels of normal and tumor breast tissue adiponectin and serum adiponectin levels. In addition, the association of tissue and serum adiponectin levels with the various classical risk and IR factors, such as body mass index, menopausal status and, tumor size, stage, lymph node status, hormonal status were also studied. Results: Tumor tissue adiponectin levels (56 ± 9.6 ng/ml) were similar with normal breast tissue (56 ± 10 ng/ml) (p>0.05). However, the serum adiponectin levels were significantly lower compared with both normal and tumor tissue (p<0.05). In addition, the inversely association of serum adiponectin levels with tumor tissue adiponectin levels was detected (p=0.001). The inverse correlation between T stage and tumor tissue adiponectin was found (p=0.03). The levels of serum adiponectin were significantly more higher in patients with c- erb-B2 overexpressed (p=0,008). Both nuclear and histologic grade were significantly associated with serum adiponectin levels (p=0.04,p=0.04, respectively). On the other hand, the reverse relationship between nuclear grade and, both tumor (p=0.01) and normal tissue (p=0.009) adiponectin levels was also detected. In subgroup analysis, the correlation among demographic, clinicopathologic, IR parameters, tissue and serum adiponectin levels was not found (p>0.05). Conclusions: Our results suggest that the low serum adiponectin and high normal and tumor tissue adiponectin levels detected in breast cancer patients and serum adiponectin levels inversely associated with tumor tissue adiponectin levels. No significant financial relationships to disclose.


2016 ◽  
Vol 16 (4) ◽  
pp. 485-495 ◽  
Author(s):  
Danielle Larouche ◽  
Mirette Hanna ◽  
Sue-Ling Chang ◽  
Simon Jacob ◽  
Bernard Têtu ◽  
...  

Chronic inflammation may be a causative factor in breast cancer. One possible underlying mechanism is the generation of oxidative stress, which may favor tumorigenic processes. Antioxidant consumption may, therefore, help reduce tissue inflammation levels. However, few studies have explored this relation in breast tissue. We aimed to evaluate correlations between antioxidant (vitamin A/retinol, vitamin C, vitamin E, β-carotene, α-carotene, lycopene, lutein/zeaxanthin, β-cryptoxanthin, selenium, and zinc) intakes and protein expression levels of interleukin (IL)-6, tumor necrosis factor-α, C-reactive protein, cyclooxygenase-2, leptin, serum amyloid A1, signal transducer and activator of transcription 3, IL-8, IL-10, lactoferrin, and transforming growth factor-β measured in the normal breast tissue of 160 women diagnosed with breast cancer. Antioxidant intakes were collected using a self-administered food frequency questionnaire. Inflammation marker expression was assessed by immunohistochemistry. Correlations between antioxidant intakes and inflammatory marker expression were evaluated using Spearman’s partial correlation coefficients ( r) for all women and for premenopausal and postmenopausal women separately. After Bonferroni correction, negative correlations were observed between dietary β-tocopherol and IL-10 expression in all women combined ( r = −0.26, P = .003) and among postmenopausal women ( r = −0.39, P = .003). For all women, a negative correlation was found between total zinc intakes and IL-10 ( r = −0.26, P = .002). Among postmenopausal women, dietary selenium intake was negatively correlated with the expression of lactoferrin ( r = −0.39, P = .003). No associations were observed in premenopausal women. Our findings suggest that consumption of specific antioxidants, including β-tocopherol, zinc, and selenium, may act on the breast tissue through mechanisms affecting the expression of some inflammation markers, particularly among postmenopausal women.


2020 ◽  
Vol 64 (1) ◽  
pp. 15-27
Author(s):  
M. Ibragimova ◽  
M. Tsyganov ◽  
L. Pisareva ◽  
N. Litvyakov

The assessment of the etiological role of viruses in the development of breast cancer remains the subject of intense study. This review examines the data on the presence/absence of viral infection in breast cancer tumors and its clinical significance. The reports on the association of breast cancer with three groups of viruses: HMTV (human Mammary Tumor Virus / MMTV-like), Epstein-Barr virus (EBV) and human papillomavirus (HPV) were analyzed. The authors carried out meta-analysis for each type of virus, which demonstrated the association of the viral infection with breast cancer tissue. A meta-analysis of 1389 breast cancer tissue samples and 750 normal breast tissue samples showed a high level of HMTV infection in the breast cancer tissue (30.7%). The relative risk of breast cancer associated with HMTV infection was 16.7 (95% CI: 7.0-39.7, p = 1.69x10-10). For EBV, the meta-analysis of 1131 breast tumor samples and 185 normal breast tissue samples (based on 9 primary studies) showed that the incidence of EBV infection was 30. .4% in tumor breast tissue and 4.3% in normal breast tissue. The relative risk of EBV-associated breast cancer was 3.3 (95% CI: 1.8-5.8, р=0.00006). The meta-analysis of HPV infection included 29 primary studies with 2,446 tumor tissue samples and 1,144 normal tissue samples. The prevalence of HPV in breast cancer samples and in normal tissue samples was 25% and 4.5%, respectively. The relative risk of breast cancer associated with HPV infection was 3.6 (95% CI: 2.3-5.6, p = 2.8x10-8). The data obtained indicate that the studies on the etiological role of HMTV, EBV and HPV in the development of breast cancer are promising.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 12038-12038
Author(s):  
L. A. Pires ◽  
R. Hegg ◽  
S. R. Graziani ◽  
D. G. Rodrigues ◽  
R. C. Maranhão ◽  
...  

12038 Background: Previously we described the association of PCT to a cholesterol-rich microemulsion (LDE) that binds to low-density lipoprotein (LDL) receptors and concentrates in neoplastic tissues. The association is stable, preserves the anti-proliferative activity and reduces the toxicity to animals. The present study was designed to provide preliminary toxicity data on the LDE-PCT oleate formulation, to determine its plasma kinetics compared to that of commercial PCT and to verify the complex ability to concentrate in malignant breast tissue. Methods: To determine the plasma kinetics [3H]-PCT oleate associated to LDE labeled with [14C]-Cholesteryl oleate was intravenously injected into 3 pts and [3H]-commercial PCT into 2 pts 24 h before surgery. Blood samples were collected over the 24 h to quantified radioactivity and the pharmacokinetic parameters. Tumoral and normal breast tissue were excised during the surgery. Other 3 heavily pretreated pts with breast cancer were included in this study to assess toxicity. LDE-PCT (175 mg/m2) was administered as a 1-hour infusion at 3 week interval, without pre medication. Results: Fractional clearance rate (FCR) of LDE and of the drug were similar (0.030 ± 0.026 e 0.018 ± 0.018, respectively, P = 0.5742). The uptake of both [14C]-LDE and [3H]-paclitaxel oleate by breast malignant tissue was 2 and 3 fold greater than that of the normal breast tissue. The PCT oleate T1/2 (h) was greater than the commercial PCT (T½ = 18.97 ± 7.7 and 7.34 ± 0.40) and the clearence (L/h) of PCT oleate was lesser than the commercial (CL = 1.51 ± 0.18 and 7.95 ± 4.32). No hematological or neurotoxicity was found. Nausea and anorexia grade 1 was found only in one patient. Conclusion: Most of the drug is retained in the microemulsion until its removal from the circulation. The complex is stable and has greater plasma half life and lesser clearance than those for commercial one and can be concentrated in malignant breast tissue. Furthermore, LDE-PCT showed no considerable toxicity events in the 3 patients. Although data regarding response rates were not assessed, our preliminary results suggest that LDE-PCT may be a suitable and powerful weapon to treat breast cancer patients. No significant financial relationships to disclose.


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