Characterization of malignant breast tissue of breast cancer patients and the normal breast tissue of healthy lactating women volunteers using diffusion MRI and in vivo1H MR spectroscopy

2013 ◽  
Vol 41 (1) ◽  
pp. 169-174 ◽  
Author(s):  
Rani G. Sah ◽  
Khushbu Agarwal ◽  
Uma Sharma ◽  
Rajinder Parshad ◽  
Vurthaluru Seenu ◽  
...  
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.


Medicina ◽  
2008 ◽  
Vol 44 (6) ◽  
pp. 415 ◽  
Author(s):  
Loreta Strumylaitė ◽  
Algirdas Boguševičius ◽  
Stanislovas Ryselis ◽  
Darius Pranys ◽  
Lina Poškienė ◽  
...  

Cadmium is a known human lung carcinogen, although some studies indicate a link between cadmium exposure and human breast cancer. The objective of this study was to assess cadmium concentration in breast tissue samples of patients with breast cancer and benign breast tumor. Material and methods. The concentration of cadmium was determined in breast tissue samples of 21 breast cancer and 19 benign tumor patients. Two samples of breast tissue from each patient, i.e. tumor and normal tissue close to tumor, were taken for the analysis. Cadmium was determined by atomic absorption spectrometry (Perkin-Elmer, Zeeman 3030). Results. In patients with breast cancer, the mean cadmium concentration was 33.1 ng/g (95% CI, 21.9– 44.4) in malignant breast tissue and 10.4 ng/g (95% CI, 5.6–15.2) in normal breast tissue (P=0.002). In patients with benign tumor, the corresponding values were 17.5 ng/g (95% CI, 8.4–26.5) and 11.8 ng/g (95% CI, 5.1– 18.5) (P=0.3144). There was a statistically significant difference in cadmium concentration between malignant and benign breast tissues (P=0.009). Conclusion. The data obtained show that cadmium concentration is significantly higher in malignant breast tissue as compared with normal breast tissue of the same women or benign breast tissue. Further studies are necessary to determine the association between cadmium concentration in malignant breast tissue and estrogen receptor level, and smoking.


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.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1346
Author(s):  
Jasmine Gajeton ◽  
Irene Krukovets ◽  
Santoshi Muppala ◽  
Dmitriy Verbovetskiy ◽  
Jessica Zhang ◽  
...  

The tumor microenvironment contains the parenchyma, blood vessels, and infiltrating immune cells, including tumor-associated macrophages (TAMs). TAMs affect the developing tumor and drive cancer inflammation. We used mouse models of hyperglycemia and cancer and specimens from hyperglycemic breast cancer (BC) patients to demonstrate that miR-467 mediates the effects of high blood glucose on cancer inflammation and growth. Hyperglycemic patients have a higher risk of developing breast cancer. We have identified a novel miRNA-dependent pathway activated by hyperglycemia that promotes BC angiogenesis and inflammation supporting BC growth. miR-467 is upregulated in endothelial cells (EC), macrophages, BC cells, and in BC tumors. A target of miR-467, thrombospondin-1 (TSP-1), inhibits angiogenesis and promotes resolution of inflammation. Systemic injections of a miR-467 antagonist in mouse models of hyperglycemia resulted in decreased BC growth (p < 0.001). Tumors from hyperglycemic mice had a two-fold increase in macrophage accumulation compared to normoglycemic controls (p < 0.001), and TAM infiltration was prevented by the miR-467 antagonist (p < 0.001). BC specimens from hyperglycemic patients had increased miR-467 levels, increased angiogenesis, decreased levels of TSP-1, and increased TAM infiltration in malignant breast tissue in hyperglycemic vs. normoglycemic patients (2.17-fold, p = 0.002) and even in normal breast tissue from hyperglycemic patients (2.18-fold increase, p = 0.04). In malignant BC tissue, miR-467 levels were upregulated 258-fold in hyperglycemic patients compared to normoglycemic patients (p < 0.001) and increased 56-fold in adjacent normal tissue (p = 0.008). Our results suggest that miR-467 accelerates tumor growth by inducing angiogenesis and promoting the recruitment of TAMs to drive hyperglycemia-induced cancer inflammation.


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.


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

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.


2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 21069-21069
Author(s):  
L. H. Malkas ◽  
L. A. Schnaper ◽  
B. Herbert ◽  
W. Abdel-Aziz ◽  
Y. Liu ◽  
...  

21069 Background: We have identified a novel cancer associated isoform of the protein, proliferating cell nuclear antigen (PCNA), termed (caPCNA), and demonstrated that this isoform arises through a direct protein post-translational modification, and not via genetic mutation or RNA splice variation. Our results suggest that caPCNA has the potential to serve as a highly effective and unique marker for identifying malignant breast cancer cells. Methods: This assertion is based on our proteomic-based analyses of more than 60 malignant and non- malignant breast cell lines and tissues. Commercially available antibodies against PCNA cannot distinguish between the different isoforms of PCNA present in malignant and non-malignant breast cells and cannot be used clinically to differentiate between normal and malignant breast tissue. However, we have recently developed a rabbit polyclonal antibody, (caPCNAab), which specifically recognizes only the caPCNA isoform expressed by malignant human breast cells. Results: Using this antibody we clearly show that caPCNA is expressed only in malignant breast cells and tissues, and can be found in early disease. caPCNA expression in tissues was quantified as average staining intensity X average percentage of cells stained. Using this criterion the following data were obtained: 10 cases of normal breast tissue (reduction mammoplasty) gave a total score of 1%; 35 cases of normal breast tissue adjacent to malignancy scored as 4%; 30 cases of DCIS scored as 90%; and 55 cases of invasive breast carcinoma scored as 120%. The five cases of ADH examined thus far were shown to score similar to that of normal breast tissue. Conclusions: The implication of these data is that the development of a caPCNAab-based IHC stain could potentially be used to reliably stain only in situ or invasive carcinoma, and distinguish genuinely benign lesions (e.g., ADH) from carcinoma, (e.g., DCIS) allowing definitive diagnosis in such cases where a limited amount of an atypical lesion prevents definitive diagnosis on routine H/E stained sections alone. For the patient population, this could result in a marked decrease in the need for either a repeat core biopsy or an excisional biopsy due to an inconclusive initial diagnosis. No significant financial relationships to disclose.


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