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AIM: To assess the role of Notch activation in predicting bevacizumab efficacy in colorectal cancer (CRC). MATERIALS & METHODS: Notch activation was evaluated by immunohistochemistry (IHC) on 65 CRC enrolled within randomized clinical trials assessing first-line bevacizumab-based chemotherapy and on 21 CRC treated with chemotherapy alone. RESULTS: Strong Notch (IHC 3+) activation was negatively associated with response (18 vs 62% in low Notch cases [IHC 0, 1, 2+]; p = 0.016), progression-free survival (4.9 vs 12.1 months; p = 0.002) and overall survival (19.3 vs 30.4 months; p = 0.039). No correlation was found between Notch activation and clinical outcome in CRC treated with chemotherapy alone. CONCLUSION: A potential role of Notch activation in the antitumor activity of bevacizumab could be hypothesized.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/metabolismo , Receptores Notch/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/administração & dosagem , Biomarcadores , Proteínas de Ligação ao Cálcio , Estudos de Casos e Controles , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Retratamento , Resultado do TratamentoRESUMO
Background Cancer patients are presumed a frail group at high risk to contract coronavirus disease (COVID-19). The aim of this study was to investigate the prevalence of SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection in asymptomatic cancer patients attending the outpatient clinic of a general hospital in a region with a high prevalence of SARS-CoV-2 infection (North Italy, first wave). Methods We retrospectively analyzed data of consecutive cancer patients attending the outpatient clinic of the oncology unit, General Hospital of Piacenza. All the patients having underlying cancer, without clinical suspicion of COVID-19, attending the outpatient clinic underwent nasopharyngeal swabs, from April 3, 2020 to June 3, 2020 and were included in this study. Results In a two-month period, 260 consecutive, asymptomatic (for COVID-19) cancer patients were tested for COVID-19. There were 160 women and 100 men; 218 patients were under active anticancer treatment, 32 in the diagnostic/staging phase waiting for treatment, and 10 treated with supportive care only. Ten of the 260 patients (3.85%) showed COVID-19 positivity. All but one (treated with hormone therapy) of the COVID-19 positive patients delayed anticancer treatment. The mean delay of anticancer treatment was 45.86±27.66 days (range 21-87 days), and the mean time for viral clearance was 25.7±22.68 days (range 7-79 days). All the 10 patients with COVID-19 and cancer overcame the infection, and treated patients could restart anticancer treatment. Conclusion Our data indicate a high prevalence of COVID-19 in cancer patients in an area with a high prevalence of SARS-CoV-2 infection. Routine COVID-19 testing of cancer patients when asymptomatic allowed an early detection, isolation, and treatment, avoiding viral spread among other frail patients and among medical/nurse staff.
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Endometrial cancer (EC) represents the most frequently occuring gynecological tumor worldwide. The aim of the present study was to estimate the prognostic value of triple negative phenotype (TNP) in EC, and any associations with to pathological and clinical characteristics. The present study includes 220 cases of patients with EC who underwent to surgery at the Guglielmo da Saliceto Hospital of Piacenza (Italy) and the expressions of estrogen receptor (ER), progesterone receptor (PR) and oncoprotein c-erbB-2 (HER2) expression were examined. Pearson's Chi-square and Fisher's exact test were used to evaluate the association of TNP cases with variables associated with a worse prognosis. Progression-free survival (PFS) and overall survival (OS) were analyzed with Kaplan-Meier curves. A total of 26 patients (12%) had a TNP, and these cases had a higher percentage of high-risk histology, an advanced stage of disease at the time of diagnosis, with shorter PFS and OS when compared to non-TNP. The present study confirmed that TNP represents prognostic significance in EC.
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δlike ligand 4 (DLL4)Notch signaling is associated with tumor resistance to antivascular endothelial growth factor (VEGF) therapy. Furthermore, Notch signaling is critical for the maintenance of colon cancer stem cells (CSCs), which are relevant in drug resistance and tumor angiogenesis. CD44 is a transmembrane glycoprotein and is considered a putative marker of CSCs. To assess the association of Notch intracellular cleaved domain (NICD), DLL4 and CD44 expression with the efficacy of antiangiogenic drugs, a series of samples derived from patients with advanced colon cancer enrolled in prospective clinical trials were analyzed. Histological samples from 51 primary tumors that originated from patients treated with bevacizumabbased firstline chemotherapy were analyzed by immunohistochemistry for NICD, DLL4 and CD44 expression, and CD31 for microvessel count. The expression levels of genes relevant for angiogenesis [angiopoietin (ANGPT)1, ANGPT2, fibroblast growth factor (FGF)1, FGF2, epidermal growth factor, placental growth factor, VEGFA and DLL4] were detected by reverse transcriptionquantitative PCR using RNA extracted from the frozen tissues of four tumors with low and four tumors with high NICD expression. Strong NICD levels were observed in 12/51 (24%) of the patients, whereas 16/51 (31%) of the colon cancer subjects exhibited high CD44 expression. Strong CD44 staining was associated with high NICD levels compared with the CD44 expression levels noted in samples with low NICD levels (67 vs. 20%, P=0.005). No association was observed with regards to the expression levels of NICD, CD44 and the other aforementioned biomarkers. High expression levels of NICD and CD44 predicted reduced progressionfree survival (P<0.001) and overall survival (P=0.002). No significant differences in the expression of angiogenesisrelated genes were detected between low and high NICDexpressing tumors. In conclusion, NICD and CD44 tissue levels exhibited an association and may be related to a reduced survival rate in patients with advanced colon cancer treated with bevacizumab.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Bevacizumab/administração & dosagem , Proteínas de Ligação ao Cálcio/genética , Neoplasias do Colo/tratamento farmacológico , Receptores de Hialuronatos/genética , Neovascularização Patológica/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bevacizumab/efeitos adversos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Receptores Notch/genética , Fator A de Crescimento do Endotélio Vascular/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/genéticaRESUMO
BACKGROUND AND AIM OF THE WORK: BRCA1/2 mutation carriers diagnosed with breast cancer have a strong life-time risk of developing contralateral breast cancer (CBC). We performed a population-based study with the aim of estimating the proportion of CBC associated with BRCA1/BRCA2 mutations, and the contribution of germline mutations to both molecular and clinical features of these tumors. METHODS: Fifty-five women with invasive CBC consecutively seen at the at the Genetic Oncology Service of the University Hospital of Parma from 2000 to 2011 were subjected to BRCA1/2 testing. Fifty-five case-matched, unilateral breast cancer (UBC) patients (pts), which tested negative for BRCA1/2 mutations, were selected as control group. RESULTS: BRCA mutations were detected in 13 (24%) of 55 CBC pts. Women with BRCA1 mutations, and to a lesser extent BRCA2 mutations, were significantly more likely to present with high histologic grade, negative hormone receptor status and high proliferation rate in both first and second primary breast cancers than BRCA-negative, CBC tumors. A diagnosis of triple-negative breast cancer (TNBC) was significantly more frequent in women with BRCA mutations in comparison with BRCA-negative, UBC controls. There were no survival differences between BRCA-positive and non-BRCA tumors. CONCLUSIONS: Results of the present study indicate that both first primary and second primary breast cancers in BRCA carriers are qualitatively distinct from BRCA negative CBC, and from sporadic UBC controls. These findings highlight relevant clinical considerations about the potential value of BRCA testing in women with CBC as well as therapeutic, preventive, and surveillance implications for patients carrying a mutation.
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Genes BRCA1 , Genes BRCA2 , Mutação , Neoplasias de Mama Triplo Negativas/genética , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias de Mama Triplo Negativas/mortalidade , Neoplasias de Mama Triplo Negativas/patologiaRESUMO
BACKGROUND: Primary squamous cell carcinoma (SCC) of the breast is a rare and aggressive neoplasm that constitutes approximately 0.1% of all breast carcinomas. Before the tumor can be classified as a true SCC of the breast, certain criteria need to be fulfilled. These are: i) more than 90% of the malignant cells must be of squamous cells origin; ii) tumor is independent from the overlying skin and nipple; iii) other sites of primary SCC have been excluded. CASE REPORT: We describe a case of pure SCC of the breast that arose 15 years after local radiation for a primary adenocarcinoma of the breast in a 54-year-old woman with history of bilateral breast cancer. The tumor was triple-negative with a high Ki-67 index. The patient underwent adjuvant chemotherapy with docetaxel and oral fluorouracil. CONCLUSION: There are no specific guidelines for the treatment of primary SCC of the breast. Larger series are necessary to determine if different strategies of treatment and follow-up are necessary and if prognosis is really comparable to other histotypes of cancers of the breast.
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Neoplasias da Mama/patologia , Carcinoma de Células Escamosas/patologia , Segunda Neoplasia Primária/patologia , Biópsia , Neoplasias da Mama/diagnóstico , Carcinoma de Células Escamosas/diagnóstico , Feminino , Humanos , Pessoa de Meia-Idade , Segunda Neoplasia Primária/diagnósticoRESUMO
BACKGROUND: Soft tissue sarcomas are a heterogeneous group of malignant neoplasms including several distinct entities with different cell differentiation and clinical prognosis, but which are often treated as a single disease. CASE REPORT: We report the case of a male patient, heavily treated for a metastatic well-differentiated liposarcoma occurring in the left lateral neck. He received radiotherapy and different lines of standard chemotherapy with local progression and lung metastasis. In November 2009, on the basis of a phase II study demonstrating the efficacy of sunitinib in patients with liposarcoma, the patient was treated with sunitinib at 37.5 mg daily in 4-week cycles on a compassionate use basis. Until November 2012 he received a total of 23 cycles of sunitinib treatment achieving a stable disease in all sites. Therapy with sunitinib is still ongoing without side effects. CONCLUSION: Our findings confirm that sunitinib may be a useful therapeutic tool in the treatment of some cases of pre-treated liposarcoma.