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1.
Anticancer Res ; 42(1): 253-261, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34969732

RESUMO

BACKGROUND/AIM: Many experimental studies have suggested the importance of thyroid hormones in breast cancer (BC) morphogenesis. The aim of this study was to evaluate the association of thyroid hormone levels in serum of patients with primary BC with morphological presentations of the disease in pathological specimens and prognosis. PATIENTS AND METHODS: We measured the serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), along with serum thymidine kinase 1 activity and examined their relation to pathological features and prognosis of 158 patients with primary BC. RESULTS: We found a significant positive association of serum FT3 level with the presence of carcinoma in situ component (CIS) (p=0.032) and its size (p=0.047), with the presence (p=0.022) and the number of multifocal/multicentric tumors (MMTs) (p=0.002), as well as with increased proliferative activity in terms of serum thymidine kinase 1 (p=0.002). Moreover, we report that each 1.0 unit rise of FT3/FT4 ratio×10 was associated with an odds ratio of 1.77 (95% confidence interval=1.17-3.30, p=0.007), 1.97 (95% confidence interval=1.17-2.67, p=0.010) and 1.56 (95% confidence interval=1.02-2.37, p=0.039) for the detection of patients with CIS, MMTs and lymphovascular invasion, respectively, after adjusting for age. We did not find statistically significant associations of serum TSH level with breast cancer`s parameters. A Cox regression survival analysis identified serum FT3 level >5.95 pmol/l as a risk factor for BC recurrence (relative risk=2.65, p=0.017), a finding that retained significance in a multivariate model (relative risk=2.52, p=0.027). CONCLUSION: The FT3/FT4 ratio is a valuable parameter predicting the presence of CIS, MMTs and lymphovascular invasion in pathological specimens. An elevated serum FT3 level is associated with the presence of CIS, MMTs, increased proliferative activity and poor prognosis.


Assuntos
Neoplasias da Mama/sangue , Carcinoma in Situ/sangue , Recidiva Local de Neoplasia/sangue , Glândula Tireoide/metabolismo , Hormônios Tireóideos/sangue , Adulto , Idoso , Biomarcadores Tumorais/sangue , Neoplasias da Mama/patologia , Carcinoma in Situ/patologia , Proliferação de Células/genética , Feminino , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Prognóstico , Timidina Quinase/sangue , Testes de Função Tireóidea , Glândula Tireoide/patologia , Hormônios Tireóideos/genética , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue
2.
Tumour Biol ; 43(1): 341-349, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34957976

RESUMO

BACKGROUND: Cancer progression is associated with significant systemic clinical manifestations including cachexia induced weight loss and anorexia. Pentoxifylline (PTX) is a drug that has been shown to have multiple beneficial effects in cancer patients through its anti-inflammatory properties. MAIN OBJECTIVE: To evaluate PTX effects on colon cancer patients treated with chemotherapy. PATIENTS AND METHODS: Forty metastatic colon cancer patients receiving chemotherapy were enrolled in this randomized study. 17 patients were treated with a full dose of PTX (400 mg TID), 9 patients with a reduced dose PTX (200 mg TID) and 23 served as controls (no PTX). RESULTS: Follow-up evaluations of patients included the following: physical examination; leukopenia determination; weight determination; stomatitis determination; and survival rate. Patients treated with PTX (both full and reduced doses), experienced a significant increase in weight and a reduction in stomatitis relative to the control group. Treatment with PTX also significantly increased patient survival rate. All patients treated with PTX, had a median overall survival (OS) rate of 20.4 months as compared to 13.2 months in the control group. CONCLUSIONS: PTX treatment of colon cancer patients, in addition to chemotherapy, significantly improved survival rates, induced weight gain and reduced stomatitis occurrence -all important parameters of cachexia.


Assuntos
Caquexia/prevenção & controle , Neoplasias do Colo/tratamento farmacológico , Pentoxifilina/uso terapêutico , Estomatite/prevenção & controle , Ganho de Peso/efeitos dos fármacos , Idoso , Antineoplásicos/uso terapêutico , Caquexia/tratamento farmacológico , Neoplasias do Colo/mortalidade , Progressão da Doença , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Leucopenia/prevenção & controle , Masculino , Pessoa de Meia-Idade , Pentoxifilina/efeitos adversos
3.
EJNMMI Phys ; 8(1): 63, 2021 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-34436698

RESUMO

BACKGROUND: Following each cycle of peptide receptor radionuclide therapy (PRRT), absorbed doses by tumors and normal organs are typically calculated from three quantitative single-photon emission computed tomography (SPECT)/computed tomography (CT) studies acquired at t1 = 24 h, t2 = 96 h, t3 = 168 h after the first cycle of treatment and from a single study at t1 after the subsequent cycles. In the present study, we have assessed the feasibility of a single SPECT/CT study after each PRRT cycle using a trained multiple linear regression (MLR) model for absorbed dose calculation and have evaluated its impact on patient management. Quantitative [177Lu]-DOTA-TATE SPECT/CT data after PRRT of seventy-two consecutive metastatic neuroendocrine tumors patients were retrospectively evaluated. A set of 40 consecutive studies was used to train the MLR model. The two independent variables of the model included the time of imaging after administration of the treatment and the radiopharmaceutical activity concentration in a given  organ/tumor. The dependent variable was the dose absorbed by the organ/tumor obtained with the standard protocol. For bone marrow dosimetry, the independent variables included the time of imaging, and the blood and remainder of the body activity concentration. The model was evaluated in 32 consecutive patients. Absorbed doses were assessed for kidneys, bone marrow, liver, spleen and tumor sites. RESULTS: There was no difference in management decisions, whether PRRT can be safely continued or not because unsafe absorbed dose to risk organs between the standard and the MLR model-based protocol using a single SPECT/CT study performed at t3 = 168 h after the first cycle and at t1 = 24 h after the subsequent cycles. Cumulative absorbed doses were obtained with mean relative differences of - 0.5% ± 5.4%, 1.6% ± 15.1%, - 6.2% ± 7.3%, - 5.5% ± 5.8% and 2.9% ± 12.7% for kidneys, bone marrow, liver, spleen and tumors, respectively (Pearson's r correlation coefficient 0.99, 0.91, 0.99, 0.99 and 0.97, respectively). CONCLUSION: Dosimetry calculations using a MLR model with a single SPECT/CT study are in good agreement with the standard protocol, while avoiding the use of dosimetry software and enabling improved patient comfort and reduced scanner and staff time.

4.
Harefuah ; 160(7): 419-424, 2021 07.
Artigo em Hebraico | MEDLINE | ID: mdl-34263567

RESUMO

AIMS: The aim of this study was to evaluate the predictive power of the absorbed dose to kidneys after the first course of treatment with [177Lu]-DOTA-TATE on the cumulative kidney absorbed dose after 3 or 4 cycles of treatment. BACKGROUND: Peptide receptor radionuclide therapy (PRRT) with [177Lu]-DOTA-TATE is an effective treatment for somatostatin receptor positive neuroendocrine tumors (NETs). Post-treatment scans (PTS) are required after each cycle of treatment for personalized radiation dosimetry in order to calculate the dose to organs and tumors and to ensure a cumulative absorbed dose to kidneys under a safety threshold of 25 Gy. METHODS: A total of 187 patients who completed treatment and underwent PTS for dosimetry calculation were included in this retrospective study. The correlation between the cumulative absorbed dose to the kidneys after completion of treatment and the absorbed dose after the first cycle(s) was studied. Multilinear regression analysis was performed to predict the cumulative absorbed dose by the kidneys in the subsequent cycles. An algorithm for the follow-up of the kidney absorbed dose is proposed. RESULTS: When the absorbed dose to kidneys after the first cycle of treatment is below 5.6 Gy, four cycles of treatment can be safely administered with a cumulative dose less than 25 Gy (p < 0.1). For the remaining patients, the cumulative dose absorbed after 3 or 4 cycles of treatment can be predicted after the second cycle of treatment. This protocol enabled early decisions on the number of treatment cycles and reduced the number of post-treatment SPECT/CT studies for dosimetry in 34% of patients, as well as hospitalization time for 56% of the treatment cycles. CONCLUSIONS: Assessment of the kidney absorbed dose after PRRT can be simplified with the algorithm presented in this study. This approach enabled early decisions on the number of therapy cycles in 75% of patients. DISCUSSION: The validity of these results is limited to the protocol of dosimetry calculation used in our institution. Implementation in other centers may require standardization of the acquisition parameters and the dosimetry protocol.


Assuntos
Tumores Neuroendócrinos , Exposição à Radiação , Humanos , Tumores Neuroendócrinos/radioterapia , Radioisótopos , Radiometria , Estudos Retrospectivos
5.
Cancer Rep (Hoboken) ; : e1479, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34184405

RESUMO

BACKGROUND: The standard chemotherapy treatment protocol for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) requires as long as 56 days of hospitalization over six months. Where the 5-Fluorouracil (5-FU) pump is available, most treatment will be on outpatient bases, however patients will still be under chemotherapy treatment for a comparable period of time (around 50 days). AIM: A modified protocol was assessed to decrease hospitalization and/or chemotherapy treatment time without sacrificing outcomes, to potentially increase patient quality of life. METHODS AND RESULTS: A retrospective analysis (2005-2018) of recurrent/metastatic HNSCC patients with a modified treatment protocol was performed. Treatment consisted of cisplatin, cetuximab, 5-fluorouracil bolus and leucovorin administered on day 1 of a 2-week cycle, and a continuous infusion of 5-fluorouracil on days 1-2 of the cycle. Outcomes were measured by progression-free survival, overall survival, and patient hospitalization time. Analysis was done using the Kaplan-Meier survival function curve. The study cohort consisted of 27 patients. The modified treatment protocol resulted in a median progression-free survival of nine months and median overall survival of 14 months, while hospitalization time was reduced by almost 80% in the first six months of treatment. CONCLUSIONS: Modification of the cisplatin, cetuximab, 5-FU and leucovorin protocol to a bi-weekly regimen utilizing alternative drug delivery methods, significantly reduced patient hospitalization from 56 days to 12 days in the first 6 months of treatment. This was achieved without compromising treatment outcome, while significantly reducing the days patients were exposed to chemotherapy, and thus potentially improving quality of life.

6.
J Nucl Med ; 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34049983

RESUMO

To assess the efficacy and safety of 177Lu-DOTATATE in patients with somatostatin receptor (SSR) positive lung neuroendocrine tumor (NET). Methods: This is a retrospective review of the outcome of patients with typical carcinoid (TC) and atypical carcinoid (AC), treated with 177Lu-DOTATATE at two ENETS Centres of Excellence. Morphological imaging (RECIST 1.1) and 68Ga-DOTATATE PET/CT responses were assessed at 3 months after completion of 177Lu-DOTATATE. Concordance between two response assessment methods was evaluated by Kappa statistics. Progression-free survival (PFS) and overall survival (OS) was estimated by Kaplan-Meier analysis and compared by Log-rank test. Treatment-related adverse events (AEs) were graded based on CTCAE version 5. Results: Of 48 patients (median age, 63 years, 13 female), 43 (90%) had AC and 5 (10%) TC. Almost all patients (47, 98%) were treated due to progression. Majority (40, 83%) received somatostatin analogs and 10 patients (20%) had prior everolimus, chemotherapy or both. All patients had high SSR expression (≥ modified Krenning score 3) on pre-treatment 68Ga-DOTATATE PET/CT. Patients received a median 4 (range 1-4) cycles of 177Lu-DOTATATE (33% with concurrent radiosensitizing chemotherapy) to a median cumulative activity of 27GBq (range 6-43GBq). At median follow-up of 42 months, the median PFS and OS were 23 months (95% CI 18-28 months) and 59 months (95% CI 50-not reached [NR]), respectively. Of 40 patients with RECIST-measurable disease and 39 patients with available 68Ga-DOTATATE PET/CT response categories were: partial response, 20% (95% CI 10-35%) and 44% (95% CI 30-59%); stable disease, 68% (95% CI 52-80%) and 44% (95% CI 30-59%) and progressive disease 12% (95% CI 5-27%) by both, respectively. There was a moderate concordance between response categories by RECIST and 68Ga-DOTATATE PET/CT, weighted Kappa of 0.51 (95% CI 0.21-0.68). Of patients with stable disease by RECIST, those with partial response on 68Ga-DOTATATE PET/CT had longer OS compared to those with no response, NR vs 52 months (95% CI 28-64), HR 0.2 (95% CI 0.1-0.6), p 0.001. Most grade 3/4 AEs were reversible and the most common was lymphopenia (14%) with no incidence of myelodysplasia/leukemia. Conclusion: In patients with advanced progressive lung NET and satisfactory SSR expression, 177Lu-DOTATATE is effective and safe with a high disease control rate and encouraging PFS and OS.

7.
Res Rep Urol ; 13: 175-179, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33907693

RESUMO

Purpose: Patients treated by external beam radiotherapy (EBRT) for localized carcinoma of the prostate (CAP) often suffer from urinary obstruction. While most patients can be treated medically, some require transurethral prostatectomy (TURP) for alleviation of obstruction. The consequences of combing EBRT and TURP are controversial. The objective of this study was to evaluate the success and complication rates of TURP combined with EBRT. Patients and Methods: Between 2001 and 2017, 3501 patients underwent TURP. Sixty-six of them were treated with EBRT for CAP. Surgical complications according to the Clavien-Dindo (CD) scale and the need for secondary interventions were compared to 66 randomly selected patients operated on for benign prostatic hyperplasia (BPH). Results: Patients who underwent TURP for BPH were significantly older compared to the patients with CAP with an average of 76.4 (SD 4.3) vs 71 (SD 8.2) years, p<0.0001. Substantial post-operative complications were rare in both groups with only a single case of CD grade 3 in each group. However, patients with CAP required significantly more secondary surgeries (21% vs 6%, p=0.02) and significantly more additional interventions (37.9% vs 13.6%, p=0.0025). There was no difference in complication rate, in the need for additional interventions or in the oncological outcome when comparing patients operated before or after EBRT. Conclusion: The complication rate of TURP done before or after EBRT is low and comparable to surgery for BPH. However, the rates of secondary surgeries and additional interventions in these patients are high (40%). TURP before or after EBRT provides similar results.

8.
EJNMMI Phys ; 8(1): 13, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33580359

RESUMO

BACKGROUND: Image quality and quantitative accuracy of positron emission tomography (PET) depend on several factors such as uptake time, scanner characteristics and image reconstruction methods. Ordered subset expectation maximization (OSEM) is considered the gold standard for image reconstruction. Penalized-likelihood estimation (PL) algorithms have been recently developed for PET reconstruction to improve quantitation accuracy while maintaining or even improving image quality. In PL algorithms, a regularization parameter ß controls the penalization of relative differences between neighboring pixels and determines image characteristics. In the present study, we aim to compare the performance of Q.Clear (PL algorithm, GE Healthcare) and OSEM (3 iterations, 8 subsets, 6-mm post-processing filter) for 68Ga-DOTATATE (68Ga-DOTA) PET studies, both visually and quantitatively. Thirty consecutive whole-body 68Ga-DOTA studies were included. The data were acquired in list mode and were reconstructed using 3D OSEM and Q.Clear with various values of ß and various acquisition times per bed position (bp), thus generating images with reduced injected dose (1.5 min/bp: ß = 300-1100; 1.0 min/bp: ß = 600-1400 and 0.5 min/bp: ß = 800-2200). An additional analysis adding ß values up to 1500, 1700 and 3000 for 1.5, 1.0 and 0.5 min/bp, respectively, was performed for a random sample of 8 studies. Evaluation was performed using a phantom and clinical data. Two experienced nuclear medicine physicians blinded to the variables assessed the image quality visually. RESULTS: Clinical images reconstructed with Q.Clear, set at 1.5, 1.0 and 0.5 min/bp using ß = 1100, 1300 and 3000, respectively, resulted in images with noise equivalence to 3D OSEM (1.5 min/bp) with a mean increase in SUVmax of 14%, 13% and 4%, an increase in SNR of 30%, 24% and 10%, and an increase in SBR of 13%, 13% and 2%. Visual assessment yielded similar results for ß values of 1100-1400 and 1300-1600 for 1.5 and 1.0 min/bp, respectively, although for 0.5 min/bp there was no significant improvement compared to OSEM. CONCLUSION: 68Ga-DOTA reconstructions with Q.Clear, 1.5 and 1.0 min/bp, resulted in increased tumor SUVmax and in improved SNR and SBR at a similar level of noise compared to 3D OSEM. Q.Clear with ß = 1300-1600 enables one-third reduction of acquisition time or injected dose, with similar image quality compared to 3D OSEM.

9.
J Cancer Res Clin Oncol ; 147(5): 1335-1340, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33598797

RESUMO

BACKGROUND: Treatment regimens for patients with metastatic or recurrent post-radiation, locoregional, unresectable salivary cancer are limited. An inverse correlation between somatostatin receptor 2 (SSTR2) and the proliferating marker Ki-67 in neuroendocrine tumors has enabled a treatment plan for metastatic disease, utilizing peptide receptor radionuclide therapy. Interestingly, healthy salivary glands express high levels of SSTR2. In this study, the presence of SSTR2, its correlation with Ki-67 in glandular salivary carcinomas and the clinical applicability thereof was determined. METHODS: In the retrospective part of this study, 76 adequate tumor tissue specimens obtained from patients diagnosed with primary or metastatic salivary carcinomas between 1988 and 2016, were collected for tissue array and histologically classified. Immunohistochemistry was performed to determine the presence, relative expression and potential correlation of SSTR2 and Ki-67. The clinical significance of SSTR2 expression was determined by prospectively assessing 68Ga-DOTATATE uptake using PET-CT imaging, in patients diagnosed with metastatic salivary gland malignant tumors between 2015 and 2016. RESULTS: Sixty-three primary cancer tumors and 14 metastatic tumors were tested. All tumor subtypes were found to express SSTR2 to some extent. The highest expression was seen in Mucoepidermoid carcinoma (MEC) tissues where the majority of specimens (86.4%) expressed SSTR2. A relatively strong immunohistochemical staining score for SSTR2 was observed in MEC, adenoid cystic carcinoma and polymorphous adenocarcinoma. Interestingly, an inverse correlation between SSTR2 and Ki-67 expressions was observed (44%) in MEC tissue. Uptake of 68Ga-DOTATATE was visualized using PET-CT imaging in 40% of patients, across metastatic MEC and ACC. All observations were found to be statistically significant. CONCLUSION: This study confirms the expression of SSTR2 in glandular salivary carcinomas and an inverse correlation in expression levels between SSTR2 and Ki-67. This lays a foundation for novel treatment options in salivary metastatic cancers where SSTR2 may be a potential novel therapeutic target.


Assuntos
Receptores de Somatostatina/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Glândulas Salivares/metabolismo , Adenocarcinoma/metabolismo , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Mucoepidermoide/metabolismo , Feminino , Humanos , Imuno-Histoquímica/métodos , Antígeno Ki-67/metabolismo , Masculino , Recidiva Local de Neoplasia/metabolismo , Octreotida/análogos & derivados , Octreotida/metabolismo , Compostos Organometálicos/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Compostos Radiofarmacêuticos/metabolismo , Estudos Retrospectivos
10.
Anticancer Res ; 41(2): 949-954, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517301

RESUMO

BACKGROUND/AIM: Thyroid hormones (THs) stimulate breast cancer (BC) cell proliferation. We hypothesized that these hormones and the proliferative marker thymidine kinase 1 (TK1) represent the initial and final steps of the proliferative pathway, respectively. PATIENTS AND METHODS: We measured the serum levels of thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4), along with serum TK1 activity, in 144 newly diagnosed BC patients, and examined the associations between THs and proliferation in different BC receptor profiles. RESULTS: TK1 activity did not correlate with TSH (r=0.06, p=0.473) or FT4 levels (r=0.04, p=0.665), but did correlate with FT3 levels (r=0.28, p=0.001). Elevated FT3 (>6.0 pmol/l) predicted increased TK1 activity (>140 Du/l) after adjusting for age (odds ratio 4.1, p=0.014). We also found a significant association of the combined elevation of FT3 and TK1, assumed as a surrogate marker of accomplished proliferative signal, with triple-negative (TN) profile (p=0.003). The rates of combined FT3 and TK1 elevation in TN and ER-positive profiles were 20.0% and 1.8%, respectively (p=0.005). CONCLUSION: FT3 may be involved in proliferative signaling, as measured by TK1 activity, predominately in TN breast cancer.


Assuntos
Timidina Quinase/sangue , Tri-Iodotironina/sangue , Neoplasias de Mama Triplo Negativas/sangue , Regulação para Cima , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Tireotropina/sangue , Tiroxina/sangue
11.
Anticancer Res ; 41(2): 1083-1087, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33517319

RESUMO

BACKGROUND/AIM: Prognostic factors serve as a vital tool in the treatment of patients with head and neck cancer (HNC). The aim of this study was to evaluate the clinical potential of Thymidine-kinase-1 (TK1) marker in the prognosis of HNC patients. PATIENTS AND METHODS: We evaluated 366 blood samples from 278 HNC patients and 88 healthy controls, using an ELISA assay. Correlations of TK1 levels with disease stage, lymph node involvement and response to radiation therapy, were determined. RESULTS: In HNC patients, TK1 levels were significantly higher compared to healthy controls. Significantly higher TK1 levels were demonstrated in node positive cases and in advanced disease stages compared to node negative and early disease stages. Levels were higher prior to radiation and decreased significantly thereafter, in patients responding to treatment. Increasing levels of TK1 post-radiation were indicative of recurrence or of non-response to treatment, while decreasing levels indicated a positive response. CONCLUSION: TK1 is a tumor marker in HNC patients with the ability to assess response to therapy. High or increasing levels correlated to a poor prognosis, whereas low levels correlated to an overall increased survival.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias de Cabeça e Pescoço/radioterapia , Timidina Quinase/sangue , Regulação para Cima , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/enzimologia , Humanos , Metástase Linfática , Masculino , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Resultado do Tratamento , Regulação para Cima/efeitos da radiação
12.
Cell Mol Life Sci ; 78(6): 2771-2780, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33051777

RESUMO

Heparanase is the predominant enzyme that cleaves heparan sulfate, the main polysaccharide in the extracellular matrix. While the role of heparanase in sustaining the pathology of autoimmune diabetes is well documented, its association with metabolic syndrome/type 2 diabetes attracted less attention. Our research was undertaken to elucidate the significance of heparanase in impaired glucose metabolism in metabolic syndrome and early type 2 diabetes. Here, we report that heparanase exerts opposite effects in insulin-producing (i.e., islets) vs. insulin-target (i.e., skeletal muscle) compartments, sustaining or hampering proper regulation of glucose homeostasis depending on the site of action. We observed that the enzyme promotes macrophage infiltration into islets in a murine model of metabolic syndrome, and fosters ß-cell-damaging properties of macrophages activated in vitro by components of diabetogenic/obese milieu (i.e., fatty acids). On the other hand, in skeletal muscle (prototypic insulin-target tissue), heparanase is essential to ensure insulin sensitivity. Thus, despite a deleterious effect of heparanase on macrophage infiltration in islets, the enzyme appears to have beneficial role in glucose homeostasis in metabolic syndrome. The dichotomic action of the enzyme in the maintenance of glycemic control should be taken into account when considering heparanase-targeting strategies for the treatment of diabetes.


Assuntos
Glucuronidase/metabolismo , Síndrome Metabólica/patologia , Animais , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Ácidos Graxos Insaturados/farmacologia , Teste de Tolerância a Glucose , Glucuronidase/genética , Resistência à Insulina , Células Secretoras de Insulina/citologia , Células Secretoras de Insulina/metabolismo , Interleucina-1beta/metabolismo , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Masculino , Síndrome Metabólica/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Obesidade/metabolismo , Obesidade/patologia , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo
13.
Radiother Oncol ; 156: 275-280, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33373641

RESUMO

BACKGROUND: Osteoradionecrosis (ORN) of the jaw is currently defined by the development of osteonecrosis in head/neck irradiated patients, regardless of lesion exposure. To diagnose medication-related osteonecrosis of the jaw (MRONJ), a history of any radiation therapy to the jaw region must be ruled out. The aim of this study was to assess the accuracy of current osteonecrosis criteria, while introducing new modifications for improved diagnosis and treatment. METHODS: One hundred and forty-one necrotic lesions were analyzed from patients exposed to bone-modifying agents (BMAs) and/or received head and neck regional radiation therapy, where the maximal dose of radiation exposure to the jaw osteonecrosis site was calculated. Modified diagnostic criteria were used to reassess all cases and a comparison of outcomes was performed using Pearson's Chi-Square/Fisher's exact test. RESULTS: Only in patients with primary head and neck carcinomas did the maximal mean radiation dose in the necrotic jaw site reach ranges associated with ORN formation (>40 Gy), with individual cases showing exposures as low as 0-2 Gy. Based on the modified diagnostic criteria almost 2/3 of the necrotic cases diagnosed as ORN should be diagnosed as MRONJ. CONCLUSIONS: ORN diagnosis should only be considered in cases of radiation exposure >40 Gy to prevent misdiagnosis and suboptimal treatment. A modified criterion for MRONJ diagnosis is recommended where radiation exposure <40 Gy in the necrotic site is included. In cases with exposure >40 Gy and BMA administration, an additional modification to diagnostic criteria of 'medication- and radiation-related osteonecrosis of the jaw', should be used.


Assuntos
Conservadores da Densidade Óssea , Doenças Maxilomandibulares , Neoplasias , Osteonecrose , Osteorradionecrose , Humanos , Doenças Maxilomandibulares/diagnóstico , Doenças Maxilomandibulares/etiologia , Necrose , Osteonecrose/diagnóstico , Osteonecrose/etiologia , Osteorradionecrose/diagnóstico , Osteorradionecrose/etiologia
15.
Cancer Med ; 9(22): 8491-8497, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32960495

RESUMO

The reported results of trimodal treatment (TMT) in muscle-invasive bladder cancer vary widely. We attempted to characterize the profile of ideal candidates for this approach. Between 2000 and 2019, 105 patients (median age 78 years) with T2-4aN0M0 bladder cancer were treated with TMT and analyzed retrospectively. Mean radiotherapy dose was 62 Gy (SD 8.4). Ten pretreatment prognostic parameters were evaluated including tumor diameter on pre-TURBT CT. Multivariate analyses was performed and combination of parameters was studied. After a median follow-up of 29 months, 53 patients (50.5%) developed recurrence and 70 patients (67.7%) died. Death was disease-specific in 46 patients (65.7%). Tumor diameter was the most significant prognostic parameter with p < 0.0001 for overall, disease-specific and recurrence-free survivals. For every 1 cm increase in tumor diameter, the risk of disease-specific mortality increased by 1.57. Age, cisplatin eligibility and the Charlson Comorbidity Index were significant predictors of overall survival but not of disease-specific or recurrence-free survival. Patients who were cisplatin-eligible with a tumor diameter ≤3 cm had a 5-year disease-specific survival rate of 79.2% as opposed to 33.9% in patients without one of these features (p < 0.001). When tumor diameter exceeded 5 cm (irrelevant of all other parameters), 5-year disease-specific survival rate was only 28.2%. Patient profiles can accurately predict response to TMT. In cisplatin-eligible patients with a tumor diameter ≤3 cm, TMT provides an excellent disease-specific survival rate. In patients with a tumor diameter >5 cm TMT renders unacceptably poor treatment outcomes.


Assuntos
Antineoplásicos/uso terapêutico , Carboplatina/uso terapêutico , Quimiorradioterapia Adjuvante , Cisplatino/uso terapêutico , Tomada de Decisão Clínica , Cistectomia , Seleção de Pacientes , Neoplasias da Bexiga Urinária/terapia , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Carboplatina/efeitos adversos , Quimiorradioterapia Adjuvante/efeitos adversos , Quimiorradioterapia Adjuvante/mortalidade , Cisplatino/efeitos adversos , Cistectomia/efeitos adversos , Cistectomia/mortalidade , Progressão da Doença , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Invasividade Neoplásica , Recidiva Local de Neoplasia , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral , Neoplasias da Bexiga Urinária/mortalidade , Neoplasias da Bexiga Urinária/patologia
16.
Endocrine ; 68(1): 222-229, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32036501

RESUMO

PURPOSE: The decreased life expectancy of MEN-1 patients is mainly related to pancreatic neuroendocrine tumors (pNETs). At best, limited data is available on the natural history of MEN-1-associated pNETs, as these tumors are rare and have a wide range of biologic behavior. Our study aims to explore the clinical course of patients with MEN-1-associated pNETs and the long-term outcomes. METHODS: This longitudinal study was conducted on the MEN-1 cohort treated at our referral center over a 22-year period (1996-2018). Relevant clinical data were retrospectively analysed. RESULTS: Among the 33 MEN-1 patients included in our study, pNETs were identified in 21 subjects with a penetrance of 48% by the age of 50. Non-functioning and functioning pNETs were diagnosed in sixteen (76%) and five (24%) patients, respectively. Two-thirds of the patients had multifocal tumors. The median number of pancreatic macroscopic lesions per individual was 4.0 ± 3.9 (range 1-8) with a mean size of 1.3 ± 2.1 cm (range 0.5-10). The metastatic rate according to the dominant pNET lesion reached 100%, 62% and 6% for tumors sized > 4 cm, 2.1-4 cm, and 1-2 cm, respectively. Over the study period, one or more therapeutic interventions for pNETs were required in 20 out of the 21 patients. pNET-related metastatic complication was the main cause of death within this MEN-1 cohort. The overall survival rate for the pNETs patients was 86% during a mean follow-up period of 8.0 ± 4.6 years. CONCLUSIONS: In our MEN-1 cohort, non-functioning pNETs were the most frequent type of pancreaticoduodenal tumor, and the tumor size correlated with the risks of metastasis and death. Increased awareness, early diagnosis, and a multidisciplinary approach may improve the associated morbidity and mortality in these patients.


Assuntos
Neoplasia Endócrina Múltipla Tipo 1 , Tumores Neuroendócrinos , Neoplasias Pancreáticas , Humanos , Estudos Longitudinais , Neoplasia Endócrina Múltipla Tipo 1/terapia , Tumores Neuroendócrinos/epidemiologia , Tumores Neuroendócrinos/terapia , Neoplasias Pancreáticas/epidemiologia , Neoplasias Pancreáticas/terapia , Estudos Retrospectivos
17.
EJNMMI Phys ; 7(1): 5, 2020 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-31975156

RESUMO

BACKGROUND: After each cycle of [177Lu]-DOTA-TATE peptide receptor radionuclide therapy (PRRT) dosimetry is performed to enable precise calculation of the radiation-absorbed dose to tumors and normal organs. Absorbed doses are routinely calculated from three quantitative single-photon emission computed tomography (SPECT) studies corrected by computed tomography (CT) acquired at t1 = 24 h, t2 = 96 h, and t3 = 168 h after the first cycle of treatment. After following cycles, a single SPECT/CT study is performed. The aim of the present study is to assess the feasibility of a "two time point" quantitative SPECT/CT protocol after the first PRRT cycle and its impact on patient management. Quantitative SPECT/CT data of 25 consecutive patients with metastatic neuroendocrine tumors after PRRT were retrospectively analyzed. Radiation-absorbed doses calculated using the standard protocol with three SPECT/CT studies acquired at (t1, t2, t3) were compared to those obtained from three different "two time point" protocols with SPECT/CT studies performed at (t1, t2), (t1, t3), or (t2, t3). RESULTS: The best agreement for the cumulative doses absorbed by the kidneys, bone marrow, liver, spleen, and tumors with the conventional protocol was obtained with the (t1, t3) protocol with mean relative differences of - 1.0% ± 2.4%, 0.4% ± 3.1%, - 0.9% ± 4.0%, - 0.8% ± 1.1%, and - 0.5% ± 2.0%, respectively, and correlation coefficients of r = 0.99 for all. In all patients, there was no difference in the management decision of whether or not to stop PRRT because of unsafe absorbed dose to risk organs using either the standard protocol or the (t1, t3) protocol. CONCLUSION: These preliminary results demonstrate that dosimetry calculations using two quantitative SPECT/CT studies acquired at 24 and 168 h after the first PRRT cycle are feasible and are in good agreement with the standard imaging protocol with no change in patient management decisions, while enabling improved patient comfort and reduced scanner and staff time.

20.
Surg Oncol ; 30: 122-125, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31500774

RESUMO

OBJECTIVES: To evaluate the utility of different Apparent Diffusion Coefficient (ADC) values on Diffused Weighted Magnetic Resonance Imaging (DW-MRI) for nasopharyngeal carcinoma (NPC). STUDY DESIGN AND SETTING: A retrospective cohort study in a single tertiary medical center. SUBJECTS AND METHODS: The study group consists of patients with pathology proven NPC that underwent DW-MRI prior or/and following a non-surgical chemo radiation treatment between the years 2007 and 2017. ADC thresholds were analyzed and compared for primary (pre-treatment) and expected post-irradiation NPC cases and healthy controls. RESULTS: We recruited 144 patients who underwent 195 MRI's for NPC. 25 DW-MRI were performed before (primary, active NPC) and 56 following (no residual NPC) treatment. 45 out of 225 patients who had brain DW-MRI for other reasons (control group) had measurable nasopharynx tissue (N = 33, adjusted for age and gender). The mean ADC of NPC prior to treatment (0.69 ±â€¯0.13 × 10-3 mm2/s) was significantly lower (ANOVA, P < 0.001) compared to the mean ADC of the adjusted controls (1.11 ±â€¯0.25 × 10-3 mm2/s) and post-treatment (1.49 ±â€¯0.28 × 10-3 mm2/s) groups. An ADC threshold of 0.805 × 10-3 mm2/s had 94% and 93.9% sensitivity and specificity rates, respectively and an odds ratio of 175[95%CI(23.25-1000)], comparing ADC levels of pre-treatment NPC patients and adjusted control group. An ADC threshold of 0.965 × 10-3 mm2/s yielded 100% positive and negative predicted values distinguishing pre-treatment and post-treatment NPC patients (free of disease). There was no statistical association between ADC levels and tumor volume/stage, nodal stage or group staging. CONCLUSIONS: ADC levels have distinct values in newly diagnosed and follow up of NPC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Imagem de Difusão por Ressonância Magnética/métodos , Carcinoma Nasofaríngeo/patologia , Recidiva Local de Neoplasia/patologia , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Prognóstico , Estudos Retrospectivos
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