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1.
J Small Anim Pract ; 63(1): 78-81, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34109622

RESUMO

An intracranial metallic foreign body (sewing needle) was diagnosed in an 11-month-old Cavalier King Charles Spaniel. Clinical evaluation showed drooling and chewing, but an otherwise normal neurological examination. Skull radiographs showed a metallic foreign body extending from the pharynx into the skull. A CT scan confirmed the presence of a foreign body crossing the right foramen lacerum into the brain. The needle was removed surgically with the aid of fluoroscopy. No complications were noted, except for transient right Horner's syndrome, most likely due to partial damage of the sympathetic postganglionic fibres that lie in the region of the tympanic bulla following surgery. The owner reported the dog being healthy 3 months after surgery.


Assuntos
Doenças do Cão , Corpos Estranhos , Animais , Encéfalo , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/cirurgia , Cães , Fluoroscopia , Corpos Estranhos/diagnóstico por imagem , Corpos Estranhos/cirurgia , Corpos Estranhos/veterinária , Agulhas/veterinária , Tomografia Computadorizada por Raios X/veterinária
2.
J Small Anim Pract ; 62(1): 59-64, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-31044432

RESUMO

A 2 month-old female cat, mixed breed, was referred for difficulty moving and severe enlargement of the mandible and limbs. Polyostotic cortical hyperostosis was diagnosed based on diagnostic imaging and histopathological changes of the mandible and limbs. Marked cortical bone thickening was detected on radiographs and CT scan images. The diaphyses of both radii and ulnae, together with the mandibular rami and bodies, were most severely affected. The many similarities shared with the human condition, Caffey's disease, are discussed.


Assuntos
Doenças do Gato , Hiperostose Cortical Congênita , Animais , Doenças do Gato/diagnóstico por imagem , Gatos , Feminino , Seguimentos , Hiperostose Cortical Congênita/diagnóstico por imagem , Hiperostose Cortical Congênita/veterinária , Mandíbula , Radiografia , Ulna
3.
Tumour Biol ; 42(6): 1010428320925301, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32489146

RESUMO

A key tool for monitoring breast cancer patients under neoadjuvant treatment is the identification of reliable predictive markers. Ki67 has been identified as a prognostic and predictive marker in ER-positive breast cancer. Ninety ER-positive, HER2 negative locally advanced breast cancer patients received letrozole (2.5 mg daily) and cyclophosphamide (50 mg daily) with/without Sorafenib (400 mg/bid daily) for 6 months before undergoing surgery. Ki67 expression and tumor size measured with caliber were determined at baseline, after 30 days of treatment and at the end of treatment. Patients were assigned to a clinical response category according to Response Evaluation Criteria in Solid Tumors, both at 30 days and before surgery and further classified as high-responder and low-responder according to the median variation of Ki67 values between biopsy and 30 days and between biopsy and surgery time. The predictive role of Ki67 and its changes with regard to clinical response and survival was analyzed. No differences in terms of survival outcomes emerged between the arms of treatment, while we observed a higher percentage of women with progression or stable disease in arm with the combination containing Sorafenib (20.5% vs 7.1%, p = 0.06). Clinical complete responders experienced a greater overall variation in Ki67 when compared with partial responders and patients with progressive/stable disease (66.7% vs 30.7%, p = 0.009). High responders showed a better outcome than low responders in terms of both disease-free survival (p = 0.009) and overall survival (p = 0.002). ΔKi67 score evaluated between basal and residual tumor at definitive surgery showed to be highly predictive of clinical complete response, and a potential parameter to be used for predicting disease-free survival and overall survival in luminal breast cancer treated with neoadjuvant endocrine-based therapy.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Antígeno Ki-67/genética , Letrozol/administração & dosagem , Prognóstico , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem da Célula/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Letrozol/efeitos adversos , Terapia Neoadjuvante , Sorafenibe/administração & dosagem , Sorafenibe/efeitos adversos , Resultado do Tratamento
4.
Breast ; 46: 19-24, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31051411

RESUMO

BACKGROUND: Endocrine treatment with Tamoxifen and aromatase inhibitors (AIs) is a staple in the management of hormone receptor positive breast cancer (HR + BC). It has become clear that HR + BC carries a consistent risk of relapse up to 15 years post-diagnosis. While increasing evidence supports the use of extended adjuvant Tamoxifen over 5 years, controversial data are available on the optimal duration of extended AIs adjuvant treatment. We performed a meta-analysis to assess the real impact of extended adjuvant therapy with AIs on disease-free survival (DFS). METHODS: A literature-based meta-analysis of randomized controlled trials (RCTs) was undertaken. Relevant publications from PubMed, the Cochrane Library, and abstracts from American Society of Clinical Oncology (ASCO) and San Antonio Breast Cancer (SABCS) symposia were searched. Primary and secondary endpoints were Disease Free Survival (DFS) and overall survival (OS) respectively. A subgroup analysis was also performed to elucidate the impact of nodal involvement. RESULTS: The pooled analysis revealed a significant increase in DFS in the extended AIs group (hazard ratio (HR): 0.78, 95% CI: 0.68-0.90; P = 0.0006). The subgroup analysis according to nodal status showed a greater DFS benefit with extended AIs in patients with positive nodes (HR = 0.67 versus 0.80). Our analysis also demonstrated no improvement in OS with extended AIs (HR = 0.99, 95%CI: 0.87-1.12; P = 0.84). CONCLUSION: This work confirmed the efficacy of extended adjuvant treatment with AIs for HR + early breast cancer, with a 22% increase in DFS, but no impact on OS. Greater efficacy was observed in women with positive nodal status.


Assuntos
Antineoplásicos Hormonais/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Inibidores da Aromatase/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Tamoxifeno/administração & dosagem , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Modelos de Riscos Proporcionais , Ensaios Clínicos Controlados Aleatórios como Assunto , Receptor ErbB-2/metabolismo , Resultado do Tratamento
5.
Breast ; 29: 55-61, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27428471

RESUMO

BACKGROUND: Histological status of axillary lymph nodes is an important prognostic factor in patients receiving surgery for breast cancer (BC). Sentinel lymph node (SLN) biopsy (B) has rapidly replaced axillary lymph node dissection (ALND), and is now the standard of care for axillary staging in patients with clinically node-negative (N0) operable BC. The aim of this study is to compare pretreatment lymphoscintigraphy with a post primary systemic treatment (PST) scan in order to reduce the false-negative rates for SLNB. METHODS: In this single-institution study we considered 170 consecutive T2-4 N0-1 M0 BC patients treated with anthracycline-based PST. At the time of incisional biopsy, we performed sentinel lymphatic mapping. After PST, all patients repeated lymphoscintigraphy with the same methodology. During definitive surgery we performed further sentinel lymphatic mapping, SLNB and ALND. RESULTS: The SLN was removed in 158/170 patients giving an identification rate of 92.9% (95% confidence interval (CI) = 88.0-96.3%) and a false-negative rate of 14.0% (95% CI = 6.3-25.8%). SLNB revealed a sensitivity of 86.0% (95% CI = 74.2-93.7%), an accuracy of 94.9% (95% CI = 90.3-97.8%) and a negative predictive value of 92.7% (95% CI = 86.1-96.8%). CONCLUSION: Identification rate, sensitivity and accuracy are in accordance with other studies on SLNB after PST, even after clinically negative node conversion following PST. This study confirms that diagnostic biopsy and neoadjuvant chemotherapy maintain breast lymphatic drainage unaltered.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Linfocintigrafia/métodos , Linfonodo Sentinela/diagnóstico por imagem , Adulto , Idoso , Antraciclinas/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Axila , Neoplasias da Mama/terapia , Reações Falso-Negativas , Feminino , Humanos , Excisão de Linfonodo , Pessoa de Meia-Idade , Terapia Neoadjuvante , Valor Preditivo dos Testes , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela
6.
Aust Vet J ; 93(12): 460-5, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26449394

RESUMO

CASE REPORT: An 8-year-old spayed female cross-breed dog was evaluated following a 2-month history of thoracic limb weakness. Neurological examination revealed a spinal cord lesion between C1 and C5 segments. Magnetic resonance imaging (MRI) revealed that almost 70% of the spinal canal between C1 and C2 was occupied by an intradural extramedullary mass that was connected to a paraspinal mass from the cranial aspect of C2 to the cranial aspect of C3. The dog was anaesthetised and a dorsal, right-sided hemilaminectomy was performed. A durotomy was performed to expose a multilobular mass located principally along the right dorsal-lateral aspect of the spinal cord. The mass did not appear to infiltrate the cord parenchyma. The abnormal tissue was removed as completely as possible using gentle dissection and submitted for histological evaluation. The histological findings were consistent with an intradural-extramedullary haemangioblastoma with paraspinal extension. Following surgery, no neurological deterioration was detected. A metronomic-dosing chemotherapy protocol was administered to prevent progression or recurrence of the tumour. Follow-up MRI studies were performed 3, 6 and 12 months after the surgery, confirming complete tumour removal and the absence of recurrence. CONCLUSION: Haemangioblastoma is an extremely rare neoplasm in animals and only two cases of this tumour have been reported, but in other anatomical locations. Haemangioblastomas in human patients are more commonly located in the cerebellum and intradural-extramedullary growth is extremely rare. The dog in this study responded favourably to combined surgery and metronomic chemotherapy and was clinically normal 1 year after surgery.


Assuntos
Vértebras Cervicais/patologia , Vértebras Cervicais/cirurgia , Doenças do Cão/diagnóstico , Hemangioblastoma/veterinária , Animais , Antineoplásicos/uso terapêutico , Medula Cervical/patologia , Medula Cervical/cirurgia , Doenças do Cão/tratamento farmacológico , Doenças do Cão/cirurgia , Cães , Feminino , Hemangioblastoma/diagnóstico , Hemangioblastoma/tratamento farmacológico , Hemangioblastoma/cirurgia , Laminectomia/veterinária , Resultado do Tratamento
7.
Br J Cancer ; 112(1): 52-60, 2015 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-25461806

RESUMO

PURPOSE: To assess whether the combination of letrozole, metronomic cyclophosphamide and sorafenib (LCS) is well tolerated and shows activity in primary breast cancer (BC). METHODS: Thirteen oestrogen receptor-positive, postmenopausal, T2-4, N0-1 BC patients received the LCS combination for 6 months. In these patients we examined the pharmacokinetics of sorafenib and cyclophosphamide, toxicity of the regimen, the clinical response to therapy and changes in the levels of biologically relevant biomarkers. RESULTS: Adequate plasma concentrations of sorafenib were achieved in patients when it was dosed in combination with L+C. The mean plasma concentrations of C were consistently lower following administration of LCS, compared with administration of L+C only. The most common drug-related grade 3/4 adverse events were skin rash (69.3%), hand-foot skin reaction (69.3%) and diarrhoea (46.1%). According to RECIST Criteria, a clinical complete response was observed in 6 of 13 patients. A significant reduction in tumour size, evaluated with MRI, was also observed between baseline and 14 days of treatment in all 13 patients (P=0.005). A significant reduction in SUV uptake, measured by (18)FDG-PET/CT, was observed in all patients between baseline and 30 days of treatment (P=0.015) and between baseline and definitive surgery (P=0.0002). Using modified CT Criteria, a response was demonstrated in 8 out of 10 evaluable patients at 30 days and in 11 out of 13 evaluable patients at the definitive surgery. A significant reduction in Ki67 expression was observed in all patients at day 14 compared with baseline (P<0.00001) and in 9 out of 13 patients at the definitive surgery compared with baseline (P<0.03). There was also a significant suppression of CD31 and VEGF-A expression in response to treatment (P=0.01 and P=0.007, respectively). CONCLUSIONS: The LCS combination is feasible and tolerable. The tumour response and target biomarker modulation indicate that the combination is clinically and biologically active.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Administração Metronômica , Idoso , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacocinética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Ciclofosfamida/farmacocinética , Feminino , Humanos , Letrozol , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Niacinamida/análogos & derivados , Niacinamida/farmacocinética , Nitrilas/administração & dosagem , Nitrilas/efeitos adversos , Nitrilas/farmacocinética , Compostos de Fenilureia/administração & dosagem , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/farmacocinética , Ensaios Clínicos Controlados Aleatórios como Assunto , Sorafenibe , Triazóis/administração & dosagem , Triazóis/efeitos adversos , Triazóis/farmacocinética
8.
Br J Cancer ; 111(1): 46-54, 2014 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-24874483

RESUMO

BACKGROUND: Stratification of patients for treatment of ductal carcinoma in situ (DCIS) is suboptimal, with high systemic overtreatment rates. METHODS: A training set of 95 tumours from women with pure DCIS were immunostained for proteins involved in cell survival, hypoxia, growth factor and hormone signalling. A generalised linear regression with regularisation and variable selection was applied to a multiple covariate Cox survival analysis with recurrence-free survival 10-fold cross-validation and leave-one-out iterative approach were used to build and test the model that was validated using an independent cohort of 58 patients with pure DCIS. The clinical role of a COX-2-targeting agent was then tested in a proof-of-concept neoadjuvant randomised trial in ER-positive DCIS treated with exemestane 25 mg day(-1)± celecoxib 800 mg day(-1). RESULTS: The COX-2 expression was an independent prognostic factor for early relapse in the training (HR 37.47 (95% CI: 5.56-252.74) P=0.0001) and independent validation cohort (HR 3.9 (95% CI: 1.8-8.3) P=0.002). There was no significant interaction with other clinicopathological variables. A statistically significant reduction of Ki-67 expression after treatment with exemestane ± celecoxib was observed (P<0.02) with greater reduction in the combination arm (P<0.004). Concomitant reduction in COX-2 expression was statistically significant in the exemestane and celecoxib arm (P<0.03) only. CONCLUSIONS: In patients with DCIS, COX-2 may predict recurrence, aiding clinical decision making. A combination of an aromatase inhibitor and celecoxib has significant biological effect and may be integrated into treatment of COX2-positive DCIS at high risk of recurrence.


Assuntos
Androstadienos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Inibidores da Aromatase/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/enzimologia , Carcinoma Intraductal não Infiltrante/tratamento farmacológico , Carcinoma Intraductal não Infiltrante/enzimologia , Ciclo-Oxigenase 2/biossíntese , Androstadienos/administração & dosagem , Neoplasias da Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Celecoxib , Estudos de Coortes , Ciclo-Oxigenase 2/genética , Inibidores de Ciclo-Oxigenase 2/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Recidiva Local de Neoplasia/enzimologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Pirazóis/administração & dosagem , Sulfonamidas/administração & dosagem , Análise de Sobrevida
9.
Br J Cancer ; 110(9): 2209-16, 2014 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-24722179

RESUMO

BACKGROUND: Although Trastuzumab has improved survival of HER2+ breast cancer patients, resistance to the agent pre-exists or develops through the course of therapy. Here we show that a specific metabolism and autophagy-related cancer cell phenotype relates to resistance of HER2+ breast cancer to Trastuzumab and chemotherapy. METHODS: Twenty-eight patients with locally advanced primary breast cancer were prospectively scheduled to received one cycle of Trastuzumab followed by a new biopsy on day 21, followed by taxol/Trastuzumab chemotherapy for four cycles before surgery. FDG PET/CT scan was used to monitor tumour response. Tissue samples were immunohistochemically analysed for metabolism and autophagy markers. RESULTS: In pre-Trastuzumab biopsies, the LC3A+/HER2+ cell population was correlated with HIF1α expression (P=0.01), while GLUT1 and LC3B expression were correlated with Ki67 proliferation index (P=0.01 and P=0.01, respectively). FDG PET tumour dimensions before therapy were correlated with LC3B expression (P=0.005). Administration of Trastuzumab significantly reduced clinical and PET-detected tumour dimensions (P<0.01). An inverse association of tumour response with the percentage of cells expressing HIF1α at baseline was documented (P=0.01). Administration of Trastuzumab resulted in a decrease of the proliferation index (P=0.004), GLUT1 (P=0.04) and HER2 (P=0.01) expression. In contrast, the percentage of LC3A+/HER2+ cells was increased (P=0.01). High baseline HIF1α expression was the only parameter associated with poorer pathological response to preoperative chemotherapy (P=0.001). CONCLUSIONS: As the HER2+/LC3A+ phenotype, which often overexpresses HIF1α, is a major subpopulation increasing after therapy with Trastuzumab, LC3A- and HIF1α-targeting therapies should be investigated for the augmentation of anti-HER2 therapy efficacy.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Antineoplásicos/uso terapêutico , Autofagia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Subunidade alfa do Fator 1 Induzível por Hipóxia/fisiologia , Anticorpos Monoclonais Humanizados/administração & dosagem , Neoplasias da Mama/patologia , Feminino , Fluordesoxiglucose F18 , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Proteínas Associadas aos Microtúbulos , Terapia Neoadjuvante , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Estudos Retrospectivos , Trastuzumab
10.
Br J Cancer ; 108(8): 1587-92, 2013 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-23579222

RESUMO

BACKGROUND: The objective of this study was to determine the optimal scheduling of 2.5 mg daily letrozole in neoadjuvant breast cancer patients to obtain pathological complete response (pathCR) and assess Ki-67 expression as an early predictor of response. PATIENTS AND METHODS: This single institution study comprised 120 oestrogen receptor (ER)-positive postmenopausal women with primary breast cancer (clinical stage ≥ T2, N0-1), from three sequential cohorts (cohort A of 40, cohort B of 40 and cohort C of 40 patients, respectively) based on different duration of the neoadjuvant letrozole. Biological markers such as ER, progesterone receptor, HER2 and Ki-67 expression were tested at diagnosis and at definitive surgery. RESULTS: A total of 89 patients (75.4%) achieved an objective response with 44 (37.3%) clinical CRs and 45 (38.1%) partial responses. The clinical CRs were significantly observed in cohort C (23 out of 40 patients, 57.5%) and B (16 out of 38 patients, 42.1%) compared with cohort A (5 out of 40 patients, 12.5%) (P-value for trend <0.001). Letrozole induced a similar significant reduction in Ki-67 index after treatment in all cohorts. The pathCR rate was significantly more frequent in cohort C (7 out of 40 patients, 17.5%) than in cohort A (1 out of 40 patients, 2.5%) and B (2 out of 40 patients, 5.0%) (P-value for trend <0.04). CONCLUSION: One-year neoadjuvant letrozole therapy leads to a higher pathCR rate and may be the optimal length of drug exposure.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Nitrilas/administração & dosagem , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Triazóis/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Inibidores da Aromatase/administração & dosagem , Inibidores da Aromatase/efeitos adversos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Estudos de Coortes , Esquema de Medicação , Feminino , Humanos , Antígeno Ki-67/biossíntese , Antígeno Ki-67/metabolismo , Letrozol , Terapia Neoadjuvante , Nitrilas/efeitos adversos , Triazóis/efeitos adversos
11.
Br J Cancer ; 98(11): 1753-8, 2008 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-18506177

RESUMO

Persistent circadian rhythm of bone turnover in bone metastatic breast cancer suggests greater skeletal retention of bisphosphonates if administered in the night. We assessed differential effects of night vs morning administration of zoledronic acid (ZA) on bone turnover. Forty-four breast cancer patients with bone metastases were randomised to receive intravenous ZA (4 mg) at 1100 or 2300 hours every 28 days for four times. Urinary concentration N-telopeptide of type-I collagen (NTX) and deoxypyridinolines, and serum C-telopeptide of type-I collagen (CTX), bone alkaline phosphatase (ALP), osteocalcin and Parathyroid hormone (PTH) was measured in the morning at baseline and after 4, 7, 14, 28, 56 and 84 days. Urinary ZA concentration was also measured. Zoledronic acid caused significant decreases of NTX and CTX (P<0.001), without any difference in percent changes between night and morning arms. Bone ALP and osteocalcin were also significantly affected by ZA (P=0.001), without any difference between arms. Parathyroid hormone significantly increased in both the arms; PTH increase was lower in the night arm (P=0.001). From the second administration onwards, urinary ZA level was significantly higher in the night arm (P<0.01). Administration of ZA at two opposite phases of the circadian cycle causes similar changes of bone-turnover marker levels, but has differential effects on the level of serum PTH.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Remodelação Óssea/efeitos dos fármacos , Neoplasias da Mama/patologia , Colágeno Tipo I/sangue , Difosfonatos/administração & dosagem , Imidazóis/administração & dosagem , Hormônio Paratireóideo/sangue , Peptídeos/sangue , Adulto , Idoso , Fosfatase Alcalina/sangue , Cálcio/sangue , Ritmo Circadiano , Colágeno Tipo I/urina , Difosfonatos/urina , Feminino , Humanos , Imidazóis/urina , Pessoa de Meia-Idade , Osteocalcina/sangue , Peptídeos/urina , Ácido Zoledrônico
12.
Osteoporos Int ; 19(1): 113-7, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17703272

RESUMO

UNLABELLED: The variability of serum osteoprotegerin (OPG) and soluble RANKL (sRANKL) along the 24-h cycle was assessed in 20 healthy women. No rhythmic variations of serum OPG, sRANKL or sRANKL/OPG ratio were detected as a group phenomenon. Timing of sampling is unlikely to influence the results of measurements of circulating OPG and sRANKL. INTRODUCTION: Physiological bone turnover shows diurnal variations. The aim of the study was to assess variability of OPG and sRANKL serum levels along the 24-h cycle. METHODS: Blood was collected from 20 healthy women (median age 31 years, range 25-65 years) at 4-h intervals between 08:00 and 24:00 and at 2-h intervals between 24:00 and 08:00. Serum albumin, cortisol, osteocalcin (OC), C-terminal telopeptide of type I collagen (CTX), OPG and total sRANKL were measured. Temporal variations were assessed by the COSINOR model. RESULTS: Circadian rhythms of cortisol and albumin documented a normal synchronization within the circadian structure. Serum OC and CTX showed rhythmic variations, peaking at night-time. Rhythmic variations of serum OPG, sRANKL and sRANKL/OPG ratio were not detected as a group phenomenon. On an individual basis, rhythmic changes were detected in ten patients for OPG and eight patients for sRANKL, with very small amplitudes and heterogeneous acrophases. CONCLUSIONS: The absence of consistent rhythmic variations of circulating OPG and sRANKL levels may reflect the absence of rhythmic variations of their expression in the bone microenvironment. Were this the case, the nocturnal rise of bone resorption should be accounted for by different, not RANKL/OPG-mediated factors. Since circulating OPG and sRANKL may derive from sources other than bone, rhythmicity could be masked by non-rhythmic or non-synchronized rhythmic expression in these sources. Timing of sampling is unlikely to influence the results of measurements of circulating OPG and sRANKL.


Assuntos
Remodelação Óssea/fisiologia , Ritmo Circadiano , Osteoprotegerina/sangue , Ligante RANK/sangue , Adulto , Idoso , Colágeno Tipo I/sangue , Feminino , Humanos , Hidrocortisona/sangue , Pessoa de Meia-Idade , Osteocalcina/sangue , Albumina Sérica/química
13.
Endocr Relat Cancer ; 12(2): 383-92, 2005 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15947110

RESUMO

This study was designed to address whether simultaneous primary chemo-hormonal therapy provides additional activity compared with chemotherapy alone in breast cancer patients with operable or locally advanced disease. Between January 1997 and January 2002, 211 consecutive patients with T2-4, N0-1, M0 breast cancer were randomized to receive either epirubicin alone (EPI) or epirubicin plus tamoxifen (EPI-TAM). Ki67 expression was evaluated immunohistochemically in tumor specimens obtained before chemotherapy by incision biopsy and at definitive surgery. Tumor shrinkage of >50% was obtained in 76% of patients randomized in the EPI arm and 81.9% of patients randomized in the EPI-TAM arm (not significant). The corresponding rates of clinical and pathological complete response were 20.2 and 21.9% (not significant), and 4.8 and 6.7% (not significant), respectively. Pathologically complete response was more frequently observed in estrogen receptor (ER)-negative (ER-) tumors (P=0.04) and correlated with elevated baseline Ki67 expression (P<0.01). Both EPI and EPI-TAM treatments resulted in a significant reduction in Ki67 expression, either in overall patients (P=0.000) or in patients with ER+ breast cancer (P=0.000). The reduction in Ki67 immunostaining in the EPI-TAM arm was greater than in the EPI arm, leading to a lower Ki67 expression at post-operative residual histology (P=0.0041). The addition of tamoxifen to epirubicin chemotherapy did not improve the response rate but led to a significantly higher reduction in the Ki67 expression. Baseline elevated Ki67 expression and the ER- status were both associated with a greater chance of obtaining a pathological complete response at residual histology.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Epirubicina/uso terapêutico , Tamoxifeno/uso terapêutico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Feminino , Humanos , Antígeno Ki-67/análise , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Tamoxifeno/administração & dosagem , Tamoxifeno/efeitos adversos
14.
Br J Cancer ; 89(6): 977-82, 2003 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-12966412

RESUMO

The purpose of this study was to evaluate whether tumour response to primary chemotherapy in human breast cancer is influenced by baseline haemoglobin (Hb) status. A total of 157 patients with T2-4, N0-1 M0 breast cancer were treated with chemotherapy consisting of either the CMF regimen + tamoxifen (the first 76 cases) or the single-agent epirubicin (the subsequent 81) before definitive surgery. In total, 144 patients were fully assessable. Ki67, p53, bcl-2, c-erbB2, steroid hormone receptor, and microvessel density were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery. Tumour shrinkage >50% occurred in 72.1% of patients. Responding patients had higher baseline Hb levels and red blood cell counts than nonresponders (P<0.01 and <0.003, respectively). The distribution of disease response according to increasing cutoffs of baseline Hb status showed that from 12.5 mg l(-1) onwards, patients with Hb levels above the cutoff obtained a greater response rate than those with lower Hb values. The difference attained the statistical significance at 12.5 (76.1 vs 59.5%, P<0.05) and 13.0 g/dl(-1) (81.0 vs 57.6%, P<0.002) cutoffs, respectively. The predictive role of Hb levels was maintained in multivariate analysis after adjustment for clinical and biological characteristics and treatment regimen. Patients with baseline Hb levels

Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Mama/tratamento farmacológico , Hemoglobinas/análise , Antígenos CD/metabolismo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/sangue , Neoplasias da Mama/cirurgia , Ciclofosfamida/uso terapêutico , Epirubicina/uso terapêutico , Contagem de Eritrócitos , Feminino , Fluoruracila/uso terapêutico , Humanos , Técnicas Imunoenzimáticas , Antígeno Ki-67/análise , Metotrexato/uso terapêutico , Receptores de Estrogênio/análise , Receptores de Progesterona/análise , Tamoxifeno/uso terapêutico , Resultado do Tratamento , Proteína Supressora de Tumor p53/análise
15.
Br J Cancer ; 85(8): 1106-12, 2001 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-11710821

RESUMO

The association between tumour shrinkage and reduction in kinetic cell activity after primary chemotherapy in human breast cancer is still a matter of investigation. 157 patients with T2-4, N0-1, M0 breast cancer received primary chemotherapy consisting of either the CMF regimen + tamoxifen (the first consecutive 76 cases) or the single agent epirubicin (the subsequent 81). Ki67, p53, bcl2, c-erbB2 and steroid hormone receptors were evaluated immunohistochemically in tumour specimens obtained before chemotherapy and at surgery. Tumour shrinkage of >50% occurred in 72.4% of patients. Ki67 expression significantly decreased after chemotherapy; the reduction correlated with tumour response in both univariate (P < 0.005) and multivariate analysis (P = 0.02). p53, bcl-2, steroid hormone receptor and c-erbB2 immunostaining were scarcely affected. Baseline bcl2 (P = 0.04) and c-erbB2 (P = 0.02) were directly and inversely associated with the reduction in Ki67 immunostaining, respectively. Baseline p53 expression (P < 0.01) was directly related with Ki67 expression at residual tumour, whereas oestrogen receptor expression (P < 0.001) was inversely related. Ki67 at residual tumour was a better predictor for relapse-free survival (RFS) than baseline Ki67. Clinical response (P < 0.03), but not reduction in Ki67, was a significant independent predictor for disease recurrence. Chemotherapy was found to induce tumour shrinkage and to reduce the number of cells in the cell cycle, but its effect on tumour biology/aggressiveness was minimal. Reduction in Ki67 immunostaining correlated with clinical response but failed to be related to RFS. Ki67 expression at surgery rather than at baseline appears to be a better predictor for disease relapse.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Antígeno Ki-67/análise , Adulto , Idoso , Neoplasias da Mama/química , Neoplasias da Mama/mortalidade , Feminino , Humanos , Imuno-Histoquímica , Pessoa de Meia-Idade , Análise Multivariada , Proteínas Proto-Oncogênicas c-bcl-2/análise , Receptores de Estrogênio/análise , Taxa de Sobrevida , Proteína Supressora de Tumor p53/análise
16.
Breast Cancer Res Treat ; 69(2): 143-51, 2001 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-11759820

RESUMO

The response to primary chemotherapy is an important prognostic factor in patients with non metastatic breast cancer. In this study we compared the assessment of response performed by clinical palpation to that performed by echography and mammography in 141 out of 157 consecutive breast cancer patients (T2-4, N0-1, M0) submitted to primary chemotherapy. A low relationship was recorded between tumor size assessed clinically and that evaluated by either mammography: Spearman R = 0.38 or echography: R = 0.24, while a greater correlation was found between the tumor dimension obtained by the two imaging techniques (R = 0.62). According to the WHO criteria, the grade of response of breast cancer to primary chemotherapy, showed by mammography and echography, was less marked than the grade of response seen at clinical examination. Residual tumor size assessed clinically depicted a stronger correlation with pathological findings (R = 0.68) than the residual disease assessed by echography (R = 0.29) and mammography (R = 0.33). Post-chemotherapy histology evaluation revealed pathological complete response in three cases (2.1%). Two of these cases were judged as complete responders by clinical palpation but only one was recognized by mammography, and none by echography. Clinical response, but not the response obtained by the two imaging techniques, was a significant predictor for longer disease free survival (p = 0.04). To conclude, physical examination measurements remain the method of choice in evaluating preoperatively the disease response in trials of primary chemotherapy. Prediction of pathological outcome is not improved by echography and mammography.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Mamografia/normas , Ultrassonografia/normas , Adulto , Idoso , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Pessoa de Meia-Idade , Exame Físico , Valor Preditivo dos Testes , Prognóstico , Resultado do Tratamento
17.
Minerva Chir ; 48(10): 565-9, 1993 May 31.
Artigo em Italiano | MEDLINE | ID: mdl-8396226

RESUMO

The authors present a case of Caroli's disease complicated with multiple lithiasis and cholangiocarcinoma. They analyse the etiopathogenesis and the anatomopathologic features of this uncommon disease and express some diagnostic and therapeutic considerations.


Assuntos
Adenoma de Ducto Biliar/complicações , Neoplasias dos Ductos Biliares/complicações , Ductos Biliares Intra-Hepáticos , Doença de Caroli/complicações , Colelitíase/complicações , Humanos , Masculino , Pessoa de Meia-Idade
18.
Surg Gynecol Obstet ; 162(1): 25-9, 1986 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-2416068

RESUMO

The results of studies which indicate that splenic resection of residual parenchyma is able to regenerate are based primarily upon the weight increase of the splenic remnant at specified times after partial resection. This study was done to determine the histologic characteristics of the residual splenic tissue at 30 and 90 days after partial splenectomy in rats. The average increase in weight of the splenic polar residual after subtotal resection was 43 per cent at 30 days and 44 per cent at 90 days, and 10 per cent at 30 days and 30 per cent at 90 days for residual half spleen after hemisplenectomy. Histologic alterations, mainly present in the parenchyma near the section surface at 30 days were clearly inflammatory secondary to surgical trauma. There was no regenerative significance. At 90 days, the results of histologic study demonstrate a readjustment of the vascular net and the lymphoid tissue of the white pulp. The result is new structures which reproduces the follicular morphologic characteristics. This process requires 90 days to predominate over inflammatory postsurgical changes. Only during this phase may it have an important role in determining the increase of the residual weight. Further research into the functional capacity of the newly formed structures is necessary to confirm that the histologic modifications observed are comparable to true regeneration.


Assuntos
Regeneração , Baço/fisiologia , Animais , Atrofia/patologia , Hemorragia/patologia , Hiperplasia/patologia , Macrófagos/patologia , Masculino , Tamanho do Órgão , Ratos , Ratos Endogâmicos , Esclerose/patologia , Baço/irrigação sanguínea , Baço/patologia , Esplenectomia , Coloração e Rotulagem , Fatores de Tempo
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