Mammography is currently the standard breast cancer screening procedure, even though it is constrained by low specificity in the detection of malignancy and low sensitivity in women with dense breast ...tissue. Modern imaging modalities, such as magnetic resonance imaging (MRI), have been developed in an effort to replace or complement mammography, because the early detection of breast cancer is critical for efficient treatment and long-term survival of patients. Nuclear medicine imaging technology has been introduced in the field of oncology with the development of positron emission tomography (PET), positron emission tomography/computed tomography (PET/CT) and, ultimately, positron emission mammography (PEM). PET offers the advantage of precise diagnosis, by measuring metabolism with the use of a radiotracer and identifying changes at the cellular level. PET/CT imaging allows for a more accurate assessment by merging the anatomic localization to the functional image. However, both techniques have not yet been established as diagnostic tools in early breast cancer detection, primarily because of low sensitivity, especially for sub-centimeter and low-grade tumors. PEM, a breast-specific device with increased spatial resolution, has been developed in order to overcome these limitations. It has demonstrated higher detectability than PET/CT and comparable or better sensitivity than MRI. The ability to target the lesions visible in PEM with PEM-guided breast biopsy systems adds to its usability in the early diagnosis of breast cancer. The results from recent studies summarized in this review indicate that PEM may prove to be a useful first-line diagnostic tool, although further evaluation and improvement are required.
Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL) expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 ...(MMP-9) is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL) during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity.
The study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays.
Women with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p < 0.003, NGAL: p < 0.008 MMP-9/NGAL: p < 0.01). Significant correlations were observed between MMP-9 and NGAL serum levels and breast disease severity score (r = 0.229, p < 0.006 and r = 0.206, p < 0.01, respectively), whereas a non-significant correlation was found for their complex. MMP-9, NGAL and their complex MMP-9/NGAL levels were not correlated with either Body Mass Index (BMI) or age of patients.
These findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Purpose: The purpose is to investigate the prophylactic effect of intravesically instillated recombinant IFN-γ against recurrence
of superficial transitional cell carcinoma of the bladder and to ...evaluate its effect in local immune response, presumably
mediating its therapeutic efficacy.
Experimental Design: We prospectively randomized in two groups 123 patients with initially diagnosed superficial transitional cell carcinoma and
stage Ta, T1, grade 2 tumors, who underwent transurethral tumor resection (TUR). In group A, 60 patients received IFN-γ (1.5
× 10 7 IU/instillation), whereas 63 patients, consisting of the control group B, received mitomycin C (40 mg/instillation). The
annual administration schedule consisted of eight weekly followed by four biweekly and then by eight monthly instillations
for both regimens. We also analyzed the immunophenotype of the intratumoral and intramural leukocytes by immunohistochemical
and flow-cytometric techniques. To this purpose, tumor samples were obtained at TUR and random biopsies at TUR and during
cystoscopy at 6 and 12 months, and bladder washings were collected before TUR and at preselected time points.
Results: In group A, 44 of 60 (73.4%) patients, and in group B, 36 of 63 (57.2%) patients, were tumor free during the median follow-up
period of 26.5 months (range, 3–49 months). IFN-γ was well tolerated. Six months after starting treatment, follicular cystitis
was detected in patients responding to IFN-γ. Αfter IFN-γ instillations, statistically significant increases in T cells, T-helper
cells, T-cytotoxic cells, natural killer cells, and total leukocytes, as well as in the number of B cells expressing intercellular
adhesion molecule-1 and total leukocytes expressing HLA-DR, were observed by flow cytometry in tissue specimens and bladder
washings.
Conclusions: Recombinant IFN-γ appears to be effective against stage Ta, T1, grade 2 bladder tumors’ recurrence. Recruitment and activation
of intramural leukocytes seem to be involved in the mechanism of IFN-γ action.
Summary
Differentiated thyroid cancer (DTC) is the most common malignancy of the endocrine system. There has been a significant increase in its incidence over the past two decades attributable mainly ...to the use of more sensitive diagnostic modalities. Ultrasound‐guided fine needle aspiration cytology is the mainstay of diagnosis of benign disorders and malignancy. However, approximately 20% of lesions cannot be adequately categorized as benign or malignant. In the postoperative setting, monitoring of thyroglobulin (Tg) levels has been employed for the detection of disease recurrence. Unfortunately, Tg antibodies are common and interfere with Tg measurement in this subset of patients. Despite this limitation, Tg remains the sole widely used thyroid cancer biomarker in the clinical setting. In an attempt to bypass antibody interference, research has focused mainly on mRNA targets thought to be exclusively expressed in thyroid cells. Tg and thyroid stimulating hormone receptor (TSHR) mRNA have been extensively studied both for discerning between benign disease and malignancy and in postoperative disease surveillance. However, results among reports have been inconsistent probably reflecting considerable differences in methodology. Recently, microRNA (miRNA) targets are being investigated as potential biomarkers in DTC. MiRNAs are more stable molecules and theoretically are not as vulnerable as mRNA during manipulation. Initial results have been encouraging but large‐scale studies are warranted to verify and elucidate their potential application in diagnosis and postoperative surveillance of thyroid cancer. Several other novel targets, primarily mutations and circulating cells, are currently emerging as promising thyroid cancer circulating biomarkers. Although interesting and intriguing, data are limited and derive from small‐scale studies in specific patient cohorts. Further research findings demonstrating their value are awaited with anticipation.
Heat-shock protein 90 (HSP90) is an abundant protein in mammalian cells. It interacts with a variety of proteins that play key roles in breast neoplasia. This is the first study to assess serum ...levels of HSP90 in atypical ductal hyperplasia (ADH), lobular neoplasia (LN), ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC) and infiltrative lobular carcinoma (ILC).
Serum concentrations of HSP90 in women with benign (n=34), ADH (n=26), DCIS (n=30), IDC (n=29), LN (n=20) and ILC (n=9) lesions were determined with immunoenzymatic assays. For the evaluation of serum concentrations along the transition from benign through precursor and preinvasive to invasive lesion, the severity of diagnosis was treated as an ordinal variable.
No significant association was demonstrated between serum HSP90 levels and the severity of the lesion in ductal and lobular series. The post hoc comparison between the lobular and ductal precursor lesions (i.e. ADH vs. LN) did not yield a statistically significant difference. Similarly, the post hoc comparison between the lobular and ductal invasive carcinomas (i.e. IDC vs. ILC) did not point to a statistically significant difference.
This is the first study evaluating HSP90 serum levels in both lobular and ductal lesions of the breast. Contrary to published pathological findings according to which HSP90 exhibits significant variability along both series, such a finding was not replicated for the level of serum HSP90 concentrations.
Irisin is a recently discovered myokine, involved in the browning of white adipose tissue. To date, its function has been mainly associated with energy homeostasis and metabolism, and it has been ...proposed as a promising therapeutic target for obesity and metabolic diseases. This is the first study investigating the role of irisin in human breast cancer.
Participants included one hundred and one (101) female patients with invasive ductal breast cancer and fifty one (51) healthy women. Serum levels of irisin, leptin, adiponectin and resistin were quantified in duplicates by ELISA. Serum levels of CEA, CA 15-3 and Her-2/neu were measured on an immunology analyzer. The association between irisin and breast cancer was examined by logistic regression analysis. The feasibility of serum irisin in discriminating breast cancer patients was assessed by ROC curve analysis. Potential correlations with demographic, anthropometric and clinical parameters, with markers of adiposity and with breast tumor characteristics were also investigated.
Serum levels of irisin were significantly lower in breast cancer patients compared to controls (2.47 ± 0.57 and 3.24 ± 0.66 μg/ml, respectively, p < 0.001). A significant independent association between irisin and breast cancer was observed by univariate and multivariate analysis (p < 0.001). It was estimated that a 1 unit increase in irisin levels leads to a reduction in the probability of breast cancer by almost 90%. Irisin could effectively discriminate breast cancer patients at a cut-off point of 3.21 μg/ml, with 62.7% sensitivity and 91.1% specificity. A positive association with tumor stage and marginal associations with tumor size and lymph node metastasis were observed (p < 0.05, p < 0.01, p < 0.01, respectively).
Our novel findings implicate irisin in breast cancer and suggest its potential application as a new diagnostic indicator of the presence of disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is one of the most frequently mutated human tumor suppressor genes, implicated in cell growth and survival and suppressing tumor ...formation. Loss of PTEN activity, either at the protein or genomic level, has been related to many primary and metastatic malignancies including breast cancer. The present study investigates the heterozygosity, mutation spectrum and protein expression of PTEN in 43 patients with breast cancer or precursor lesions of the breast and 10 healthy individuals. Microsatellite analysis at the PTEN locus using D10S215, D10S541 and D10S579 markers indicated that the observed heterozygosity (Ho) is lower than the expected heterozygosity (Hs) in benign and malignant breast disease. Mutational analysis in exons 1, 5, 7 and 9 of the PTEN gene revealed several mutations, most of which cause truncation of the PTEN protein and consequently loss of activity. Increased circulating levels of PTEN and phosphorylated PTEN protein were also observed by immunostaining in patients with breast cancer and precursor breast lesions. In support, increased PTEN protein expression was detected in corresponding tissue specimens. Our data suggest an association between breast cancer and PTEN mutations, resulting in the production of truncated forms of the corresponding protein, thus indicating that breast carcinogenesis is potentially related to PTEN loss of activity rather than loss of expression. Peripheral blood sampling may provide an advantageous application for the determination of PTEN gene mutations and its protein expression in human cancer.
Purpose
Ductal endoscopy is valuable for the differential diagnosis of bloody nipple discharge; however, the pain associated with this procedure has not been evaluated. This study aims to assess the ...pain experienced by patients during ductal endoscopy.
Methods
We studied a consecutive series of women who underwent ductal endoscopy, to investigate the cause of bloody nipple discharge. The procedure was performed using standard local anesthesia (lidocaine 1% 10 ml without epinephrine, involving nipple block and periaureolar administration). Patients were asked to score the level of pain with a visual analog scale, 1, 4, 7, 12, 17, 22, 27, and 32 min after the procedure, and describe their overall and maximum pain.
Results
This series comprised 20 women aged from 27 to 68 years old. The overall pain (mean ± SE) score was equal to 5.8 ±0.3, and the maximum pain score was 8.3 ± 0.2. The peak of pain corresponded with when the dilator was inserted through the sphincter. The group in which the dilator was inserted after 4 min experienced more intense maximum and overall pain after 7, 12, 17 and 22 min.
Conclusions
Pain is an important factor in ductal endoscopy, and peaks relatively early. A standard, baseline local lidocaine dose of greater than 10 ml may be necessary at the beginning of the procedure. Late insertion of the dilator seems to be an indicator of the force of the procedure.
Breast and prostate constitute organs of intense steroidogenic activity. Clinical and epidemiologic data provide strong evidence on the influence of androgens and estrogens on the risk of typical ...hormone-dependent malignancies, like breast and prostate cancer. Recent studies have focused on the role of androgen metabolites in regulating androgen concentrations in hormone-sensitive tissues. Steroid glucuronidation has been suggested to have a prominent role in controlling the levels and the biological activity of unconjugated androgens. It is well-established that serum levels of androgen glucuronides reflect androgen metabolism in androgen-sensitive tissues. Quantitative analysis of androgen metabolites in blood specimens is the only minimally invasive approach permitting an accurate estimate of the total pool of androgens. During the past years, androgen glucuronides analysis most often involved radioimmunoassays (RIA) or direct immunoassays, both methods bearing serious limitations. However, recent impressive technical advances in mass spectrometry, and particularly in high performance liquid chromatography coupled with mass spectrometry (LC–MS/MS), have overcome these drawbacks enabling the simultaneous, quantitative analysis of multiple steroids even at low concentrations. Blood androgen profiling by LC–MS/MS, a robust and reliable technique of high selectivity, sensitivity, specificity, precision and accuracy emerges as a promising new approach in the study of human pathology. The present review offers a contemporary insight in androgen glucuronides profiling through the application of LC–MS/MS, highlighting new perspectives in the study of steroids and their implication in hormone-dependent malignancies.
Background
Thyroid disorders, including thyroid cancer and autoimmune thyroid diseases, have been closely associated with inflammation.
Objective
This study aims to investigate the role of ...inflammation in thyroid disease by assessing serum cytokine levels in patients with malignant and benign thyroid conditions.
Methods
Serum levels of ten interleukins (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12 and IL-13) were quantitatively determined in 20 patients with thyroid cancer, 38 patients with benign thyroid disease and 50 healthy controls by multiplex technology.
Results
Serum IL-1β, IL-2, IL-4, IL-5 and IL-6 levels were strongly associated with each other. IL-10 and IL-12 correlated with IL-1β, IL-5, IL-6, and with each other. Age was inversely correlated with serum levels of IL-2, IL-4 and IL-13. A positive correlation between T3 and IL-13 levels was also observed. Significantly higher levels of IL-6, IL-7, IL-10 and IL-13, as well as significantly lower levels of IL-8 were observed in patients with benign and malignant thyroid disease compared to controls. The combination of IL-13 and IL-8 in a two-marker panel was highly efficient in discriminating thyroid disorders (AUC 0.90).
Conclusions
Malignant and benign thyroid conditions are associated with altered expression levels of interleukins, supporting the association between thyroid disease and underlying inflammatory processes.
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