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Experts emphasize that colorectal cancer (CRC) incidence and mortality are increasing. That is why its early detection is of the utmost importance. Patients with cancer diagnosed in earlier stages have a better prognosis and a chance for faster implementation of treatment. Consequently, it is vital to search for new parameters that could be useful in its diagnosis. Therefore, we evaluated the usefulness of CXCL5, CXCL14 and CXCL16 in serum of 115 participants (75 CRC patients and 40 healthy volunteers). Concentrations of all parameters were measured using Luminex. CRP (C-reactive protein) levels were determined by immunoturbidimetry, while levels of classical tumor markers were measured using CMIA (Chemiluminescence Microparticle Immunoassay). Concentrations of CXCL5 were statistically higher in the CRC group when compared to healthy controls. The diagnostic sensitivity, specificity, positive and negative predictive value, and area under the ROC curve (AUC) of CXCL5 and CXCL14 were higher than those of CA 19-9. Obtained results suggest the usefulness of CXCL5 and CXCL16 in the determination of distant metastases and differentiation between TNM (Tumor-Node-Metastasis) stages, as well as the usefulness of CXCL14 and CRP combination in CRC detection (primary or recurrence). However, further studies concerning their role in CRC progression are crucial to confirm and explain their diagnostic utility and clinical application as biomarkers.
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Neoplasias Colorretais , Humanos , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/metabolismo , Antígeno CA-19-9 , Quimiocina CXCL16 , Quimiocina CXCL5 , Quimiocinas CXC , Neoplasias Colorretais/sangue , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Prognóstico , Curva ROCRESUMO
The CXCL1/CXCR2 and CXCL8-CXCR1/CXCR2 axes are under intensive investigation as they appear to regulate the progression and invasion of colorectal cancer (CRC). Growing evidence demonstrates the elevated expression of these proteins in CRC. However, a majority of relevant studies have been performed on CRC tissues using immunohistochemical techniques. Our study is the first to evaluate the diagnostic significance of serum CXCL1 and CXCR1 levels in CRC patients in comparison to well-established tumor markers, such as the carcinoembryonic antigen (CEA), and markers of inflammation, such as C-reactive protein (CRP). Thus, the aim of our study was to assess whether circulating serum levels of CXCL1 and CXCR1 might be candidates for novel biomarkers in the diagnosis and progression of CRC. The study was performed on 76 subjects, including patients with CRC and healthy volunteers as a control group. Serum concentrations of CXCL1, CXCR1, and the classical tumor marker (CEA) were measured using immunoenzyme assays, while CRP levels were assessed with the immunoturbidimetric method. Serum CXCL1 levels were statistically significantly increased in CRC patients when compared to healthy subjects, and similar results were found for CEA and CRP levels. The percentage of elevated concentrations of CXCL1 and CXCR1 was higher than that of the classical tumor biomarker and increased in the combined measurement of these proteins with CEA. In addition, among all proteins tested, serum CXCL1 seems to be the best indicator in the differentiation between CRC patients with nodal involvement and patients without the presence of lymph node metastasis. Our preliminary results indicate the role of serum CXCL1 and CXCR1 in the diagnosis of CRC, particularly in the combined measurement with CEA.
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ONCOBREAST-TEST is a diagnostic and therapeutic procedure that is part of the comprehensive care of a patient with breast cancer.: Chemosensitivity of cancer cells was assessed using the MTT test, morphological assessment of cells, LDH activity in the culture medium, and flow cytometry technique (apoptosis, proliferation, CD24, CD44, GATA3, cytokeratin, Ki-67). Diagnostic tools included panels of simple tests which could be used to accurately predict the chemosensitivity of tumor cells previously isolated from a patient, even before actual chemotherapy. The proposed procedure allows for a simple (based on MTT results, cell morphology, LDH concentration), minimally invasive, quick, and accurate assessment of the sensitivity of breast cancer cells to the drugs used and, to select the most effective treatment plan as part of personalized therapy. In a patient with NOS G3, the most promising therapy will be docetaxel with cyclophosphamide and in the case of a patient with NOS G1, paclitaxel alone and in combination with trastuzumab. The implementation of such a procedure would undoubtedly increase the effectiveness of chemotherapy, reduce side effects by excluding drugs that are ineffective before using them, protect the patient's health, and shorten the treatment time, bringing economic and social benefits.
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Introduction: Acute kidney injury (AKI) is a frequent postoperative complication. However, data on the incidence of AKI in patients with colorectal cancer (CRC) undergoing surgery with curative intent are still limited. We examined the relationship between postoperative AKI among CRC surgery patients and preoperative therapy or no prior therapy. Material and methods: A total of 326 consecutive patients from the regional oncology center undergoing CRC surgery in the period January to December 2019 were included in the observational cohort study. We defined AKI as a 50% increase in plasma creatinine or initiation of renal replacement therapy within 7 days after surgery or an absolute increase in creatinine of 0.3 mg/dl within 48 hours. Results: Acute kidney injury occurred in 36 patients (11%), 27 of whom underwent rectum resection, and 9 underwent colon resection. The incidence of AKI was identical in both types of surgery. Among 54 patients undergoing neoadjuvant radiochemotherapy, 6 patients (11%) developed AKI, while there was no case of AKI in 31 patients with neoadjuvant radiotherapy. Among 36 patients with AKI, 33 had hypertension, 27 had diabetes and 18 had at least stage 3 of chronic kidney disease before the surgery. Conclusions: Acute kidney injury after surgery for CRC is a relatively frequent postoperative complication, in particular, in patients with prior impairment in kidney function and comorbidities such as hypertension and diabetes. Appropriate preoperative therapy, including optimal hydration, withdrawal of potentially nephrotoxic drugs, etc., may reduce the incidence of AKI.
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Colorectal cancer (CRC) is a common and mortal disease. Chronic kidney disease (CKD) is the relatively common comorbidity among cancer patients affecting the available therapy and outcomes. However, data on prevalence of CKD in patients with CRC undergoing surgery is limited. The aim of the study was to evaluate the prevalence of CKD in a cohort of 560 consecutive patients with CRC undergoing surgical treatment with curative intent. Neoadjuvant therapy in a form of radiotherapy or radiochemotherapy was administered before the surgery in 67 patients and in 86 patients, respectively. Results: CKD was reported in 10%, diabetes in 25%, and hypertension in 60%, while anemia was reported in 47%. The patients with CKD were more likely to be older and anemic with higher serum CRP, which reflects a general inflammatory state. Relative to patients without this therapy, patients undergoing neoadjuvant radiochemotherapy were older, had significantly lower eGFR and albumin, and higher creatinine, aspartate aminotransferase and INR, before the surgery. All CKD patients, except two, were older than 65 years of age. Conclusions: In order to ensure the best possible outcomes, CKD should be diagnosed and treated appropriately in oncology patients to prevent complications, so they may continue their therapy with the least interruption or discontinuation of treatment.
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Colorectal cancer (CRC) is one of the most frequently diagnosed neoplasms. Despite the advances in diagnostic tools and treatments, the number of CRC cases is increasing. Therefore, it is vital to search for new parameters that could be useful in its diagnosis. Thus, we wanted to assess the usefulness of selected CC chemokines (CCL2, CCL4, and CCL15) in CRC. The study included 115 subjects (75 CRC patients and 40 healthy volunteers). The serum concentrations of all parameters were measured using a multiplexing method (Luminex). The CRP levels were determined by immunoturbidimetry, and the classical tumor markers (CEA and CA 19-9) were measured using CMIA (chemiluminescent microparticle immunoassay). The concentrations of all parameters were higher in the CRC group when compared to the healthy controls. The diagnostic sensitivity, specificity, positive and negative predictive value, and area under the ROC curve (AUC) of all estimated CC chemokines were higher than those of CA 19-9. Interestingly, the obtained results also suggest CCL2's significance in the determination of local metastases and CCL4's significance in the determination of distant metastases. However, further studies concerning the role of selected CC chemokines in the course of colorectal cancer are necessary to confirm and to fully clarify their diagnostic utility and their clinical application as markers of CRC development.
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Colorectal cancer (CRC) is one of the most common malignancies. Despite the availability of diagnostic tests, an increasing number of new cases is observed. That is why it is very important to search new markers that would show high diagnostic utility. Therefore, we made an attempt to assess the usefulness of eotaxins, as there are few studies that investigate their significance, in patients with CRC. The study included 80 subjects (CRC patients and healthy volunteers). Serum concentrations of all eotaxins were measured using a multiplexing method (Luminex), while CCR3 was measured by immunoenzymatic assay (ELISA). CRP levels were determined by immunoturbidimetry and classical tumor marker levels (CEA and CA 19-9) and were measured using chemiluminescent microparticle immunoassay (CMIA). The highest usefulness among the proteins tested showed CCR3. Its concentrations were significantly higher in the CRC group than in healthy controls. The diagnostic sensitivity, specificity, positive and negative predictive value, and the area under the ROC curve (AUC) of CCR3 were higher than those of CA 19-9. The maximum values for sensitivity, negative predictive value, and AUC were obtained for a combination of CCR3 and CRP. Our findings suggest the potential usefulness of CCR3 in the diagnosis of CRC, especially in combination with CRP or CEA.
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BACKGROUND: Colorectal cancer (CRC) is a common and lethal disease. Hypertension is the most commonly reported comorbidity among cancer patients. Data on its incidence and prevalence is very scarce. OBJECTIVES: The aim of the study was to evaluate the prevalence of hypertension and chronic kidney disease (CKD) in a cohort of 100 consecutive patients with CRC undergoing primary surgical treatment. MATERIAL AND METHODS: The pilot study included 100 consecutive patients with CRC undergoing primary surgery with curative intent within 1 year in the Department of Oncological Surgery in Bialystok, Poland. No neoadjuvant therapy was administered before the surgery. RESULTS: The prevalence of hypertension was 62% among the patients studied. Sixty-five percent of the patients were older than 65 years and hypertension was present in 78% of these elderly patients. The prevalence of CKD was 15%, while that of diabetes was 23%. All CKD patients were older than 65 years of age. The hypertensive patients were more likely to be older and anemic with higher serum fibrinogen, which reflects a general inflammatory state. Elderly hypertensive patients had significantly higher creatinine levels, lower estimated glomerular filtration rate (eGFR) levels (p < 0.001) and lower platelet counts. CONCLUSIONS: It is of the utmost importance for oncology patients to have any hypertension diagnosed and treated appropriately in order to prevent complications so they may continue their therapy with the least interruption or discontinuation of treatment and to ensure the best possible outcomes.
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Neoplasias Colorretais/cirurgia , Hipertensão/epidemiologia , Insuficiência Renal Crônica/epidemiologia , Idoso , Estudos de Coortes , Neoplasias Colorretais/complicações , Comorbidade , Creatinina/sangue , Feminino , Taxa de Filtração Glomerular , Humanos , Masculino , Projetos Piloto , Polônia/epidemiologia , Prevalência , Fatores de RiscoRESUMO
PURPOSE: Treatment with chemotherapy and targeted drugs may results in elevated risk of cardiac and renal toxicity as well as hypertension. However, data on prevalence of chronic kidney disease and hypertension in subjects with early breast cancer undergoing primary surgery are very limited. PATIENTS AND METHODS: The study aimed to assess the prevalence of chronic kidney disease and hypertension (evaluated as a preoperative assessment and defined according to ESC/ESH guidelines) in a cohort of 100 consecutive female patients with early breast cancer treated with primary surgery with curative intent. RESULTS: Patients with breast cancer were 53⯱â¯14 years of age, with serum creatinine of 0.68⯱â¯0.14â¯mg/dl and estimated glomerular filtration rate by chronic kidney disease-epidemiological collaboration formula of 99⯱â¯18â¯mL/min/1.72â¯m2. Hypertension was present in 37%, but in the elderly patients (over 65 years) the prevalence was 74%. Hypertensive females had worse kidney function as reflected by higher serum creatinine and lower estimated glomerular filtration rate, higher body mass index and fibrinogen, which reflects general inflammatory state. When we divided the patients according to age (≤ vs >65 years) and the presence of hypertension, the elderly hypertensive females had significantly worse kidney function, higher fibrinogen and fasting glucose. CONCLUSIONS: The prevalence of hypertension in patients with breast cancer raises with age, and presence of comorbidities, including chronic kidney disease. Hypertension should be treated promptly to prevent cardiovascular complications during oncological therapy.
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Neoplasias da Mama/complicações , Neoplasias da Mama/cirurgia , Hipertensão/complicações , Hipertensão/epidemiologia , Feminino , Humanos , Pessoa de Meia-Idade , Razão de Chances , PrevalênciaRESUMO
Hypertension is one of the most common comorbidities in cancer patients with malignancy, in particular, in the elderly. On the other hand, hypertension is a long-term consequence of antineoplastic treatment, including both chemotherapy and targeted agents. Several chemotherapeutics and targeted drugs may be responsible for development or worsening of the hypertension. The most common side effect of anti-VEGF (vascular endothelial growth factor) treatment is hypertension. However, pathogenesis of hypertension in patients receiving this therapy appears to be associated with multiple pathways and is not yet fully understood. Development of hypertension was associated with improved antitumor efficacy in patients treated with anti-antiangiogenic drugs in some but not in all studies. Drugs used commonly as adjuvants such as steroids, erythropoietin stimulating agents etc, may also cause rise in blood pressure or exacerbate preexisiting hypertension. Hypotensive therapy is crucial to manage hypertension during certain antineoplastic treatment. The choice and dose of antihypertensive drugs depend upon the presence of organ dysfunction, comorbidities, and/or adverse effects. In addition, severity of the hypertension and the urgency of blood pressure control should also be taken into consideration. As there are no specific guidelines on the hypertension treatment in cancer patients we should follow the available guidelines to obtain the best possible outcomes and pay the attention to the individualization of the therapy according to the actual situation.
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A long time ago, the links between renal disease and malignancy were observed, however, quite recently, their importance was recognized and 'new' subspecialty in nephrology, namely 'onconephrology' was established. In the XXI century, patients with malignancy make up the most growing number of the subjects seen for nephrology consult and/or critical care nephrology services. A plethora of renal problems may be found in patients with malignancy. They may influence not only their short-term outcomes but also the adequate therapy of the underlying oncological problem. Thus, all these kidney-related issues pose an important challenge for both specialities: oncology and nephrology. In the review a spectrum of acute and chronic renal injury caused by the malignancy is presented as well as the associations between renal disease and cancer. Assessment of kidney function and its importance in patients with malignancy is also discussed as medical oncologists should check the appropriate dose of chemotherapeutic drugs in relation to the actual renal function before prescribing them to the patients. Moreover, effects of kidney function on outcomes in oncology is presented. In addition, nephrology services should better understand both the biology of malignancy with its treatment to become a valuable part treating team to yield the best possible outcome. It is important for nephrology services to be acknowledged and to take an active participation in care of oncology patients.
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Severe adverse systemic drug events occur commonly as a result of treatment of cancer patients. Nephrotoxicity of chemotherapeutic agents remains a significant complication limiting the efficacy of the treatment. A variety of renal disease and electrolyte disorders can result from the drugs that are used to treat malignant disease. The kidneys are a major elimination pathway for many antineoplastic drugs and their metabolites. Tumour lysis syndrome, an emergency in haematooncology, occurs most often after the initiation of cytotoxic therapy in patients with high-grade lymphomas and acute lymphoblastic leukaemia. Chemotherapeutic agents can affect the glomerulus, tubules, interstitium and renal microvasculature, with clinical manifestations that range from asymptomatic elevation of serum creatinine to acute renal failure requiring dialysis. Some factors such as intravascular volume depletion, as well as concomitant use of other drugs or radiographic ionic contrast media, can potentiate or contribute to the nephrotoxicity. Cytotoxic agents can cause nephrotoxicity by a variety of mechanisms. The most nephrotoxic chemotherapeutic drug is cisplatin, which is often associated with acute kidney injury. Many other drugs such as alkylating agents, antimetabolites, vascular endothelial growth factor pathway inhibitors and epidermal growth factor receptor pathway inhibitors may have toxic effects on the kidneys. The aim of this review is to discuss the issue of nephrotoxicity associated with chemotherapy. In routine clinical practice, monitoring of kidney function is mandatory in order to identify nephrotoxicity early, allowing dosage adjustments or withdrawal of the offending drug.
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Injúria Renal Aguda/induzido quimicamente , Antineoplásicos/efeitos adversos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/fisiopatologia , Animais , Antineoplásicos/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Rim/fisiopatologia , Neoplasias/tratamento farmacológicoRESUMO
Recent studies have raised doubts about the protective role of KiSS1/KiSS1R in breast malignancy progression. However, the role of the KiSS1/KiSS1R system in primary breast cancer remains largely unknown. The aim of the present study was to characterize the biology and invasiveness potential of primary breast cancer through evaluation of KiSS1/KiSS1R protein expression and cellular localization with regard to lymph node metastasis status, receptor status (ERs, PR and HER-2/neu), and expression of aromatase, MMP-9, Ki-67 and Cyclin D1 in primary invasive breast cancer tissues. We showed increased protein expression of both KiSS1/KiSS1R and MMP-9 in the cancerous tissues compared with noncancerous tissue adjacent to the breast tumour. In the studied group of breast cancer samples, we observed a positive correlation between KiSS1 and MMP-9. We also showed a positive correlation between KiSS1R and aromatase expression in all studied breast cancers. We did not notice any associations between system and cell cycle regulators. KiSS1/KiSS1R did not correlate either with Cyclin D1 and Ki-67 or with receptor status. However, we showed higher levels of KiSS1R expression in ERα-negative cases than in ERα-positive cases in patients with lymph node metastasis. Present data do not confirm the protective role of KiSS1/KiSS1R in breast cancer progression, but our results do support the hypothesis that the KiSS1/KiSS1R system is activated even in primary breast cancer and sustained during invasion to local lymph nodes.
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Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/metabolismo , Carcinoma Lobular/metabolismo , Proliferação de Células , Kisspeptinas/metabolismo , Metástase Linfática/patologia , Receptores Acoplados a Proteínas G/metabolismo , Idoso , Idoso de 80 Anos ou mais , Mama/metabolismo , Mama/patologia , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Progressão da Doença , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Receptores de Kisspeptina-1 , Receptores de Progesterona/metabolismoRESUMO
The estrogen receptor α (ERα)-mediated pathway plays a critical role in breast cancer development and progression. KiSS1 was previously described as a metastasis suppressor gene in certain carcinomas. However, the role of KiSS1/GPR54 in breast cancer remains controversial. Whether the function of the KiSS1/GPR54 system depends on estrogen signaling in the breast cancer cell remains to be determined. This study aimed to determine the expression profiles of the KiSS1/GPR54, ERα, ERß, aromatase and cyclin D1 genes in human breast cancer tissues, and to identify a possible link between the expression levels of the studied genes and the selected clinical and pathological features. The study subjects comprised 59 females treated surgically for primary breast cancer. Total RNA was extracted from frozen breast cancer tissues, and expression levels were examined to determine any correlations. We observed strong positive correlations between the expression levels of the studied genes. The expression of ERα correlated positively with progesterone receptors (PRs), and in these tumors we also observed positive correlations between KiSS1, GPR54 and cyclin D1 mRNAs and the ERα protein. ER-positive breast tumors exhibited higher KiSS1 and GPR54 levels than the ER-negative tumors. The expression levels of the ERα and GPR54 transcripts were higher in the moderately differentiated tumors (G2) compared to the poorly differentiated high-grade (G3) cancers. We also found that HER-2/neu status in breast cancer is negatively associated with GPR54 mRNA expression. Decreasing GPR54 mRNA expression levels in HER-2/neu (+) tumors may be associated with the deregulation of the classical estrogen-mediated signaling pathway in breast tumors, and therefore, with promotion of tumor invasiveness. Our findings indicate that genes involved in the KiSS1/GPR54 system, as well as in the estrogen signaling pathway, may be utilizable molecular factors in pathogenesis studies of breast cancer.
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The chymotrypsin-like (ChT-L) activity is one of the key regulators of intracellular protein degradation. Elevated proteasome ChT-L activity has recently been reported in plasma of patients with leukemia and myelodysplastic syndrome and suggested to have a prognostic significance. The aim of the present study was to evaluate plasma proteasome ChT-L activity in patients with newly diagnosed solid tumors at early and advanced stages of the disease. The activity was assayed using the fluorogenic peptide substrate, Suc-Leu-Leu-Val-Tyr-AMC, in a cohort of 155 patients with early/advanced rectal (n=43/29), gastric (n=6/13), and breast (n=37/27) cancer and compared with that in normal individuals (n=55). The median plasma proteasome ChT-L activity was elevated by 20-32% in patients with advanced stage of rectal, gastric, and breast cancer compared with healthy donors. The difference turned out to be statistically significant (P<0.001). By contrast, values in patients with early stage of malignancies were not significantly different from those observed in normal individuals. We also found that plasma proteasome activity correlated with serum carcinoembryonic antigen levels in the group of patients with rectal cancer (r=0.433, P<0.05). Elevated plasma proteasome ChT-L activity is indicative of advanced stage of rectal, gastric, and breast cancer. However, the activity does not seem to be a parameter with clinically relevant potential in terms of early detection of cancer in this subset of patients.
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Neoplasias da Mama/sangue , Quimases/sangue , Complexo de Endopeptidases do Proteassoma/sangue , Neoplasias Retais/sangue , Neoplasias Gástricas/sangue , Adulto , Biomarcadores Tumorais/sangue , Western Blotting , Neoplasias da Mama/patologia , Antígeno Carcinoembrionário/sangue , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Retais/patologia , Neoplasias Gástricas/patologiaRESUMO
The aim of this study was assessment of possible effects of loss of heterozygosity on human genetic identification of histolopathogical tissue sections. DNA templates were extracted from tumour tissue specimens excised from oncological patients and from reference blood samples. AmpFlSTR Identifiler PCR Amplification Kit and ABI 310 Genetic Analyzer (Applera) were used to obtain genetic profiles. Frequency of LOH was calculated for respective samples. Fisher's exact test was performed for statistical analysis. Forty-two percent of the 101 cancer cases analysed were found to possess alterations of the microsatellites manifesting with allelic loss. The most frequently altered loci were D3S1358 and D18S51. The alteration was detected in 47% of cases with larynx carcinoma, 44% of cases with uveal melanoma, 60% of cases with cervical cancers, one case of liposarcoma G3 and one case od neurofibrosarcoma. No LOH was found in liposarcoma G1, dermatofibrosarcoma and cystosarcoma protuberans in either primary or recurrent tumours. In benign tumours (lipoma and fibroma) LOH was also absent. During genotyping of DNA extracted from histopathological tissue sections caution should be taken when non-match or exclusion based on few discrepancies is concluded.
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Genoma Humano/genética , Perda de Heterozigosidade/genética , Antropologia Forense , Marcadores Genéticos , Humanos , Repetições de Microssatélites/genéticaRESUMO
It was shown the functional crosstalk between ERRalpha and ERalpha in breast cancer, however, the biological significance of estrogen-related receptor alpha (ERRalpha) remains largely unclear. Therefore, we examined the expression of ERRalpha in 39 primary human breast cancer tissues and 19 matched normal tissues using RT-PCR and immunohistochemistry in the context of the aromatase, ERalpha and proliferation markers (c-myc, Ki-67) expression. Compared to the normal breast tissue, breast cancer tissues showed a slightly higher expression level of ERRalpha mRNA (mean 46.2+/-S.D.42.0, 57.7+/-S.D.58.7, respectively). However, ERRalpha mRNA levels in breast cancer tissues showed greater diversity than in normal tissues. Immunohistochemical analysis of breast cancers revealed perinuclear and cytoplasmic localization of ERRalpha. Our study shows that there is no correlation between ERRalpha and ERalpha expression. We demonstrated a positive correlation between ERRalpha and c-myc at the transcriptional level and statistically significant positive correlation between aromatase and the ERRalpha at protein level. It seems that ERRalpha could play an important role in the alternative pathway to classical estrogen receptors-dependent pathway in cell signaling. Development and use of ERRs modulators might lead in the future to design new well-tolerated and individualized therapeutic agents.
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Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Receptores de Estrogênio/genética , Aromatase/genética , Aromatase/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Estrogênio/metabolismo , Receptor ERRalfa Relacionado ao EstrogênioRESUMO
To elucidate the molecular profile of oestrogen receptors alpha and beta (ERalpha, ERbeta) we studied ERalpha and ERbeta expression at the mRNA and protein levels using real-time polymerase chain reaction (RT-PCR), Western blot analysis and immunohistochemical (IHC) methods in 41 primary breast cancers and surrounding tissues. ERalpha mRNA and ERbeta mRNA were detected in all of the breast cancer and normal matched tissues analysed. ERalpha mRNA levels showed greater diversity than ERbeta mRNA levels and the range of amount of ERbeta transcripts was far smaller than that of ERalpha. At the protein level, the percentage of ERalpha- or ERbeta-positive cases changed. Seventy percent of the tumours studied produced full-length 65 kDa ERalpha protein in Western blot analysis and 67% of assessed cases were positive in IHC. Full-length 57 kDa ERbeta protein was detected by Western blotting in 97% of analysed breast cancers, while 67% were ERbeta-positive using IHC. ERalpha was localised in the nucleus, while cytoplasmic and perinuclear localisation of ERbeta was observed in normal as well as in breast cancer cells. The amount of ERalpha (but not ERbeta) increased with age. The expression of ERalpha correlated positively with progesterone receptor and negatively with proliferation marker Ki-67. These results confirm the previous observations that the lack of ERalpha protein expression is not due to lack of ERalpha gene expression or methylation of ERalpha promoter, but due to post-transcriptional or post-translational mechanisms. Our investigation also suggests that ERalpha is more dysregulated in breast cancer, and thereby ERbeta is more tightly regulated in the tumour.
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Neoplasias da Mama/metabolismo , Receptor alfa de Estrogênio/metabolismo , Receptor beta de Estrogênio/metabolismo , Antígeno Ki-67/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Western Blotting , Neoplasias da Mama/patologia , Proliferação de Células , DNA Complementar/metabolismo , Eletroforese em Gel de Ágar , Feminino , Humanos , Pessoa de Meia-Idade , RNA Mensageiro/metabolismo , RNA Neoplásico/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: The genetic changes in DNA microsatellites - short, tandem repeat segments dispersed throughout the human genome - probably play a role in carcinogenesis. Microsatellite instability (MSI) is reflected in alterations in the patterns of these polymorphic repeat segments. In our study, human sarcomas were analyzed for the presence of microsatellite instability and loss of heterozygosity (LOH). MATERIAL/METHODS: Studies were performed on tissue specimens obtained at surgical resection from 20 patients with malignant and non-malignant soft tissue tumors (8 G1 sarcomas, 8 G3 sarcomas, 2 lipomas and 2 fibromas). Samples of venous blood from the patients served as respective controls. DNA was isolated using organic extraction. Additional microcolumn purification was performed. Fluorescent multiplex polymerase chain reaction (PCR) was used to amplify 10 microsatellite loci included in commercially available human identification kits. Microsatellite marker BAT 26 was amplified in separate PCR reactions. RESULTS: All the G3 sarcomas manifested MSI. MSI was detected on 12p in all the specimens except for recurrent synovial sarcomas. LOH in BAT 26 analysis (chromosome 2) was present in 75% of G3 sarcomas. No MSI or LOH was found in G1 sarcomas or in benign tumors. CONCLUSIONS: Genomic instability may contribute to tumorgenesis in sarcomas, and both MSI and LOH may reflect genomic instability in sarcomas. These parameters may be helpful in the differential diagnosis of malignant versus nonmalignant lesions.
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Cromossomos Humanos Par 12/genética , Cromossomos Humanos Par 2/genética , Instabilidade Genômica/genética , Perda de Heterozigosidade/genética , Repetições de Microssatélites/genética , Sarcoma/genética , Sarcoma/patologia , Marcadores Genéticos/genética , Humanos , Estadiamento de NeoplasiasRESUMO
Serum concentrations of interleukin 6 (IL-6) and C-reactive protein (CRP) were determined in 74 patients with various histological types and clinical stages of breast carcinoma, recurrent breast carcinoma and of benign breast tumor. The concentrations of IL-6 and CRP were significantly increased in carcinoma patients relative to control group and to benign breast tumor group. The frequency of higher levels and absolute value of IL-6 and CRP showed tendency to significant increase with the stage of disease. A positive correlation was observed between the concentrations of IL-6 and CRP. Our results suggest that of IL-6 assay may be useful in estimation of progress disease in patients with breast carcinoma.