Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 31
Filtrar
1.
ANZ J Surg ; 91(5): 878-884, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33506995

RESUMO

BACKGROUND: Metastatic cutaneous squamous cell carcinoma to the axilla is uncommon, with limited data to guide management. We sought to assess the outcomes of patients with this condition after surgery and radiotherapy. METHODS: A retrospective cohort study of patients treated at two Australian hospitals from 1994 through 2016 was performed. RESULTS: A total of 74 patients were identified, including 48 treated curatively with surgery-plus-radiotherapy and 15 with surgery alone. Compared with patients treated with surgery alone, a higher proportion of patients treated with surgery-plus-radiotherapy had lymph nodes larger than 6 cm (53% versus 8%, P = 0.012) and multiple adverse histopathological features (75% versus 47%, P = 0.04). The groups had similar 5-year disease-free survival (45% versus 46%) and overall survival (51% versus 48%). Presence of multiple positive lymph nodes was associated with reduced disease-free survival (hazard ratio 4.57, P = 0.01) and overall survival (hazard ratio 3.53, P = 0.02). Regional recurrence was higher in patients treated with surgery alone (38% versus 22%, P = 0.22) and patients with lymph nodes larger than 6 cm (34% versus 10%, P = 0.03). All recurrences occurred within 2 years following treatment. CONCLUSION: Combined-modality therapy for metastatic cutaneous squamous cell carcinoma to the axilla is recommended for high-risk patients, although outcomes remain modest. The key period for recurrence is within 2 years following treatment.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Cutâneas , Austrália/epidemiologia , Axila/patologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/cirurgia , Estudos de Coortes , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Metástase Linfática , Recidiva Local de Neoplasia/epidemiologia , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Cutâneas/patologia
2.
Biomark Insights ; 16: 11772719211005745, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-35173407

RESUMO

Human biobanks are recognised as vital components of translational research infrastructure. With the growth in personalised and precision medicine, and the associated expansion of biomarkers and novel therapeutics under development, it is critical that researchers can access a strong collection of patient biospecimens, annotated with clinical data. Biobanks globally are undertaking transformation of their operating models in response to changing research needs; transition from a 'classic' model representing a largely retrospective collection of pre-defined specimens to a more targeted, prospective collection model, although there remains a research need for both models to co-exist. Here we introduce the Health Science Alliance (HSA) Biobank, established in 2012 as a classic biobank, now transitioning to a hybrid operational model. Some of the past and current challenges encountered are discussed including clinical annotation, specimen utilisation and biobank sustainability, along with the measures the HSA Biobank is taking to address these challenges. We describe new directions being explored, going beyond traditional specimen collection into areas involving bioimages, microbiota and live cell culture. The HSA Biobank is working in collaboration with clinicians, pathologists and researchers, piloting a sustainable, robust platform with the potential to integrate future needs.

3.
ANZ J Surg ; 89(5): 524-528, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30414221

RESUMO

BACKGROUND: Current surgical practice often leads to excision of all papillary lesions of the breast diagnosed on percutaneous biopsy. This study aims to identify a subset of patients with papillary lesions who may be able to avoid surgery. METHODS: Between January 2000 and December 2015, 157 cases of papillary lesions with complete surgical excision pathology results were reviewed retrospectively to compare the clinical, imaging and pathology features. Of these, 50 patients with benign papillary lesions without atypia and 19 patients with benign papillary lesions with atypia on needle biopsy were analysed to determine the rate of upgrade to malignancy after surgery. RESULTS: Of the 50 patients with benign papillary lesions without atypia on biopsy, two (4%) were upgraded to low grade ductal carcinoma in situ after surgical excision. Both these patients had suspicious features on imaging. Of the 19 patients with papillary lesions with atypia diagnosed on needle biopsy, eight (42%) were upgraded to malignancy after surgery. The differences between benign, atypical and malignant papillary lesions were further compared. Malignant lesions were more suspicious radiologically (P = 0.001), more likely to have architectural distortion (P = 0.001), more peripherally located (P = 0.001) and were larger in size (P = 0.01). Patients diagnosed with malignant lesions were also older (P = 0.001). CONCLUSION: Younger patients diagnosed with small central benign papillary lesions without atypia on needle biopsy, and without suspicious imaging, may be managed conservatively with surveillance.


Assuntos
Biópsia com Agulha de Grande Calibre/métodos , Neoplasias da Mama/diagnóstico , Mama/patologia , Carcinoma Papilar/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/terapia , Carcinoma Papilar/terapia , Tratamento Conservador/métodos , Diagnóstico Diferencial , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos
4.
Int J Oncol ; 52(6): 2143-2154, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29620166

RESUMO

The 5-year survival rate for metastatic sarcoma is 16%. Although the phosphorylated human epidermal growth factor receptor (pEGFR/HER1) has been shown to be an independent predictor of overall survival in patients with sarcoma, we have previously demonstrated that sarcoma cell lines exhibit resistance, despite gefitinib blocking p-EGFR and signal transducers in EGFR downstream pathways. Gefitinib failed to decrease the ratio of phosphorylated (p-)signal transducer and activator of transcription (STAT3)/p-STAT1, suggesting that relative STAT3 abundance and activation may be involved in drug resistance. In this study, we used the panHER inhibitor, dacomitinib, to further block HER2-dependent activation, applying multiple methods, such as proliferation assay, clonogenic survival assay, anti-anoikis assay and western blot analysis. Although dacomitinib inhibited EGFR, HER2, AKT and Erk activation more effectively than gefitinib, it still only exerted minimal anti-proliferative effects on sarcoma cell lines due to the STAT3 escape pathway. However, the addition of the STAT3 inhibitor, S3I-201, to dacomitinib achieved a significant enhancement in growth inhibition, by perturbing p-STAT3/p-STAT1. Using a panel of sarcoma cell lines with different histological types, we identified that the addition of the STAT3 inhibitor enhanced the growth inhibitory effects of the panHER inhibitor, dacomitinib, on sarcoma cells. Our findings may have clinical implications on overcoming the resistance caused by the STAT3 escape pathway and optimising EGFR/panHER-targeted therapy in sarcoma.


Assuntos
Benzenossulfonatos/farmacologia , Receptores ErbB/metabolismo , Quinazolinonas/farmacologia , Fator de Transcrição STAT3/metabolismo , Sarcoma/metabolismo , Ácidos Aminossalicílicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Sinergismo Farmacológico , Humanos , Fosforilação/efeitos dos fármacos , Receptor ErbB-2/metabolismo , Sarcoma/tratamento farmacológico
5.
BMJ Open ; 8(4): e020858, 2018 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-29643165

RESUMO

OBJECTIVES: To investigate between-hospital variation in the probability of reoperation within 90 days of initial breast-conserving surgery (BCS), and the contribution of health system-level and other factors. DESIGN: Population-based, retrospective cohort study. SETTING: New South Wales (NSW), Australia. PARTICIPANTS: Linked administrative hospitalisation data were used to define a cohort of adult women undergoing initial BCS for breast cancer in NSW between 1 July 2002 and 31 December 2013. PRIMARY OUTCOME MEASURES: Multilevel, cross-classified models with patients clustered within hospitals and residential areas were used to examine factors associated with any reoperation, and either re-excision or mastectomy, within 90 days. RESULTS: Of 34 458 women undergoing BCS, 29.1% underwent reoperation within 90 days, half of which were mastectomies. Overall, the probability of reoperation decreased slightly over time. However, there were divergent patterns by reoperation type; the probability of re-excision increased alongside a concomitant decrease in the probability of mastectomy. Significant between-hospital variation was observed. Non-metropolitan location and surgery at low-volume hospitals were associated with a higher overall probability of reoperation, and of mastectomy specifically, after accounting for patient-level factors, calendar year and area-level socioeconomic status. The magnitude of association with geographical location and surgical volume decreased over time. CONCLUSIONS: Reoperation rates within 90 days of BCS varied significantly between hospitals. For women undergoing mastectomy after BCS, this represents a dramatic change in clinical course. Multilevel modelling suggests unwarranted clinical variation may be an issue, likely due to disparities in access to multidisciplinary breast cancer care and preoperative diagnostic procedures. However, the observed reduction in disparities over time is encouraging and indicates that guidelines and policy initiatives have the potential to improve regional breast cancer care.


Assuntos
Neoplasias da Mama , Reoperação , Adulto , Idoso , Idoso de 80 Anos ou mais , Austrália , Neoplasias da Mama/cirurgia , Feminino , Humanos , Armazenamento e Recuperação da Informação , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , New South Wales , Reoperação/estatística & dados numéricos , Estudos Retrospectivos
6.
Asia Pac J Clin Oncol ; 14(5): e472-e478, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29383831

RESUMO

AIM: Superficial soft tissue sarcomas (S-STS) are generally considered low-risk tumors and have an excellent prognosis when treated with appropriate surgery and adjuvant therapy. However, they are often misdiagnosed then mistreated, leading to significant morbidity. This study aims to examine the patterns of care and outcomes of patients with S-STS, comparing those initially managed through sarcoma units versus elsewhere. METHODS: Patients with S-STS from Prince of Wales Hospital in NSW (1995-2013) and Peter MacCallum Cancer Centre in Victoria (2009-2013) were identified from a national sarcoma database. Baseline variables, treatment and disease outcomes were recorded. Statistical tests performed included univariate and multivariate analyses, chi-square tests, as well as the Kaplan-Meier method for 5-year local recurrence and survival rates. RESULTS: Eighty-nine patients were identified, with 35% initially managed at a sarcoma unit and 65% elsewhere. Patients initially managed at sarcoma units had larger tumors (>5 cm 39% vs 17%; P  =  0.036) with a trend to higher grade (61% vs 48%; P = 0.39). Patients that were initially managed outside a sarcoma unit more often underwent open surgical biopsies (P < 0.0005), had multiple operations (P < 0.0005) and had higher rates of local recurrences (24% vs 6.5%, P  =  0.038). They also had lower 5-year local recurrence-free survival rates (P = 0.022), but had higher metastasis-free survival (P = 0.014). On multivariate analysis, only larger STS size and male gender predicted for poorer metastasis-free survival (P = 0.042 and 0.018, respectively). CONCLUSION: Patients with S-STS initially managed outside specialized sarcoma units undergo more operations, with risk of greater morbidity, and have greater risk of local recurrence.


Assuntos
Institutos de Câncer , Serviço Hospitalar de Oncologia , Sarcoma/terapia , Neoplasias de Tecidos Moles/terapia , Resultado do Tratamento , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Sarcoma/mortalidade , Neoplasias de Tecidos Moles/mortalidade , Taxa de Sobrevida
7.
Int J Mol Sci ; 18(6)2017 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-28556791

RESUMO

Abstract: Previous studies have shown that total epidermal growth factor receptor (EGFR) protein is highly expressed in soft tissue sarcoma (STS). We aimed to investigate the significance of phosphorylated-EGFR (pEGFR) and its activated-downstream signal transducers in STS tissue samples. A tissue microarray comprising 87 STS samples was assessed for total EGFR, pEGFR and its phosphorylated signal transducers and expression was correlated with clinicopathlogical parameters including patient outcome. Although the expression of total EGFR was significantly associated with adverse STS histologic grade (p = 0.004) and clinical stage (p = 0.012) similar to pEGFR, phosphorylated protein kinase B (pAkt) and phosphorylated extracellular signal regulated kinase (pERK), it is not a prognostic factor for survival. By contrast, the expression of pEGFR is an independent factor for cancer specific survival, while pERK is an independent prognostic factor for both overall and cancer specific survival in STS (p < 0.05, Cox proportional hazard model and log-rank test) in addition to the recognised factors of tumour grade and clinical stage. pERK and pEGFR are new independent prognostic factors for overall and/or cancer specific survival in STS. The expression of EGFR/pEGFR, and their associated downstream signal transducers, was associated with STS progression, suggesting that EGFR downstream signalling pathways may jointly support STS cell survival.


Assuntos
Receptores ErbB/metabolismo , Sarcoma/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Receptores ErbB/genética , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Fosforilação/genética , Fosforilação/fisiologia , Prognóstico , Sarcoma/genética , Sarcoma/patologia , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Adulto Jovem
8.
Onco Targets Ther ; 9: 5461-73, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27660463

RESUMO

Tyrosine kinase inhibitors (TKIs) against human epidermal growth factor receptor (EGFR/HER) family have been introduced into the clinic to treat cancers, particularly non-small-cell lung cancer (NSCLC). There have been three generations of the EGFR/HER-TKIs. First-generation EGFR/HER-TKIs, binding competitively and reversibly to the ATP-binding site of the EGFR TK domain, show a significant breakthrough treatment in selected NSCLC patients with activating EGFR mutations (actEGFRm) EGFR (L858R) and EGFR (Del19), in terms of safety, efficacy, and quality of life. However, all those responders inevitably develop acquired resistance within 12 months, because of the EGFR (T790M) mutation, which prevents TKI binding to ATP-pocket of EGFR by steric hindrance. The second-generation EGFR/HER-TKIs were developed to prolong and maintain more potent response as well as overcome the resistance to the first-generation EGFR/HER-TKIs. They are different from the first-generation EGFR/HER-TKIs by covalently binding to the ATP-binding site, irreversibly blocking enzymatic activation, and targeting EGFR/HER family members, including EGFR, HER2, and HER4. Preclinically, these compounds inhibit the enzymatic activation for actEGFRm, EGFR (T790M), and wtEGFR. The second-generation EGFR/HER-TKIs improve overall survival in cancer patients with actEGFRm in a modest way. However, they are not clinically active in overcoming EGFR (T790M) resistance, mainly because of dose-limiting toxicity due to simultaneous inhibition against wtEGFR. The third-generation EGFR/HER-TKIs selectively and irreversibly target EGFR (T790M) and actEGFRm while sparing wtEGFR. They yield promising efficacy in NSCLC patients with actEGFRm as well as EGFR (T790M) resistant to the first- and second-generation EGFR-TKIs. They also appear to have a lower incidence of toxicity due to the reduced inhibitory effect on wtEGFR. Currently, the first-generation EGFR/HER-TKIs gefitinib and erlotinib and second-generation EGFR/HER-TKI afatinib have been approved for use as the first-line treatment of metastatic NSCLC with actEGFRm. This review will summarize and evaluate a broad range of evidence of recent development of EGFR/HER-TKIs, with a focus on the second- and third-generation EGFR/HER-TKIs, in the treatment of patients with NSCLC harboring EGFR mutations.

9.
Oncotarget ; 7(16): 21496-509, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-26909593

RESUMO

Although epidermal growth factor receptor (EGFR) is often over-expressed in soft tissue sarcoma (STS), a phase II trial using an EGFR inhibitor gefitinib showed a low response rate. This study identified a new secondary resistance mechanism of gefitinib in STS, and developed new strategies to improve the effectiveness of EGFR inhibition particularly by blocking the STAT3 pathway.We demonstrated that seven STS cell lines of diverse histological origin showed resistance to gefitinib despite blockade of phosphorylated EGFR (pEGFR) and downstream signal transducers (pAKT and pERK) in PI3K/AKT and RAS/ERK pathways. Gefitinib exposure was not associated with decrease in the ratio of pSTAT3/pSTAT1. The relative STAT3 abundance and activation may be responsible for the drug resistance. We therefore hypothesized that the addition of a STAT3 inhibitor could overcome the STAT3 escape pathway.We found that the addition of STAT3 inhibitor S3I-201 to gefitinib achieved synergistic anti-proliferative and pro-apoptotic effects in all three STS cell lines examined. This was confirmed in a fibrosarcoma xenografted mouse model, where the tumours from the combination group (418mm3) were significantly smaller than those from untreated (1032mm3) or single drug (912 and 798mm3) groups.Our findings may have clinical implications for optimising EGFR-targeted therapy in STS.


Assuntos
Receptores ErbB/metabolismo , Fator de Transcrição STAT3/metabolismo , Sarcoma/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto , Ácidos Aminossalicílicos/administração & dosagem , Ácidos Aminossalicílicos/farmacologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Benzenossulfonatos/administração & dosagem , Benzenossulfonatos/farmacologia , Western Blotting , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Sinergismo Farmacológico , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Gefitinibe , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Mutação , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/farmacologia , Quinazolinas/administração & dosagem , Quinazolinas/farmacologia , Fator de Transcrição STAT3/antagonistas & inibidores , Sarcoma/tratamento farmacológico , Sarcoma/patologia , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
10.
J Endovasc Ther ; 23(2): 275-84, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26839124

RESUMO

PURPOSE: To evaluate and characterize debris retrieved from the cerebral embolic protection devices (EPDs) used during carotid artery stenting (CAS) and compare debris size, volume, tissue types, cellular composition, and protein biomarker expression in symptomatic and asymptomatic patients. METHODS: Distal protection filters were retrieved from 22 consecutive patients (mean age 71.6 years, range 52-85; 16 men) undergoing elective CAS between July 2012 and February 2014 for >70% internal carotid artery stenosis (mean 85.4% ± 10.3%). Six patients were symptomatic. The debris within each EPD was visually characterized using stereomicroscopy and then processed for histology and immunohistochemistry. Biomarkers were immunohistochemically measured to evaluate plaque stability [matrix metalloproteinase-9 (MMP-9)], inflammation [glycoprotein CD68 and interleukin-6 (IL-6)], or phenotype [smooth muscle (SM)-actin and type IV collagen]. The immunohistochemical results were measured using semiquantitative grading criteria based on both staining intensity and distribution in the samples. RESULTS: Macroscopic debris was visible in 5/22 EPDs; 3 of the 5 filters came from symptomatic patients. Microscopic debris was detected in all filters and ranged in size from 0.01 to 8.57 mm(2). Debris consisted of calcified, fibrous, and necrotic tissue, as well as fibrin and foam cells with no significant difference between the symptomatic and asymptomatic groups. There was no association between the degree or type of embolic material and stenosis severity, carotid tortuosity, calcium grade, soft plaque, or arch type. Symptomatic patients had a larger volume of debris (8.24 vs 0.58 mm(3), p<0.01), mean particle size (1.30 vs 0.32 mm(2), p<0.001), and expression of biomarkers IL-6 (2.17 vs 0.81, p<0.05), CD68 (2.00 vs 0.38, p<0.01), SM-actin (1.00 vs 0.25, p=0.055), type IV collagen (1.17 vs 0.25,p=0.082), and MMP-9 (1.00 vs 0.06, p<0.05). CONCLUSION: Histological analysis revealed particulate embolization in all EPDs used during CAS. Symptomatic patients had a larger volume of embolic debris, mean particle size, and the biomarkers associated with inflammation, necrotic core, and diminished fibrous cap.


Assuntos
Artéria Carótida Interna/química , Artéria Carótida Interna/patologia , Estenose das Carótidas/terapia , Dispositivos de Proteção Embólica , Procedimentos Endovasculares/instrumentação , Imuno-Histoquímica , Microscopia/métodos , Placa Aterosclerótica , Stents , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Artéria Carótida Interna/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/metabolismo , Estenose das Carótidas/patologia , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares/efeitos adversos , Feminino , Fibrose , Humanos , Masculino , Pessoa de Meia-Idade , Necrose , Valor Preditivo dos Testes , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Ultrassonografia Doppler Dupla
11.
Front Oncol ; 5: 2, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25674538

RESUMO

PURPOSE: Hyper-activation of the HER (erbB) family receptors, HER 1-4, leads to up-regulation of the three vital signaling pathways: mitogen activated protein kinase, phosphoinositide 3-kinase/AKT, and Janus kinase/signal transducer and activator of transcription pathways. Blocking HER1/EGFR has a limited anticancer effect due to either secondary mutation e.g., T790M or by-pass signaling of other HER members. The emergence of an anti-panHER approach to blockade of these pathways as a cancer treatment may provide a solution to this resistance. This review aimed to provide an overview of the HER signaling pathways and their involvement in tumor progression and examine the current progress in panHER inhibition. METHODS: Recent literature associated with HER signaling pathways and panHER inhibition was reviewed through PubMed and Medline database, followed by critical comparison and analysis. RESULTS: Pre-clinical studies and clinical trials of panHER inhibitors show promising results, and the potential to improve patient outcomes in solid cancers. CONCLUSION: The use of panHER inhibitors in cancers with HER-family hyper-activation, such as other epithelial cancers and sarcoma, is a new direction to research and has potential in clinical cancer therapy in the future.

12.
Anticancer Res ; 34(11): 6537-45, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25368256

RESUMO

BACKGROUND/AIM: Osteosarcoma is often a fatal malignancy. Constitutive STAT3 activation is associated with various human cancers and commonly suggests poor prognosis. We aimed to investigate the effect and potential molecular mechanisms of STAT3 inhibition on osteosarcoma. MATERIALS AND METHODS: STAT3 inhibitor S3I-201 was investigated in six osteosarcoma cell lines. Crystal violet colorimetric, clonogenic, cleaved caspase-3 assays and western blot were performed to measure the effect and mechanisms of STAT3 inhibition. RESULTS: All osteosarcoma cell lines expressed phosphorylated STAT3. Anti-proliferative effects of S3I-201 were dose- and time-dependent. S3I-201 also inhibited colony-formation and induced apoptosis through the caspase cleavage pathway. Finally, molecular mechanism studies suggested that down-regulation of STAT3 phosphorylation and downstream STAT3-target genes such as cyclin D1 and survivin may contribute to S3I-201-mediated anti-proliferation and apoptosis. CONCLUSION: Inhibition of STAT3 signalling suppressed osteosarcoma cell growth and induced apoptosis, and indicated that STAT3 targeted-therapy may have therapeutic potential in osteosarcoma.


Assuntos
Apoptose/efeitos dos fármacos , Benzenossulfonatos/farmacologia , Neoplasias Ósseas/patologia , Proliferação de Células/efeitos dos fármacos , Osteossarcoma/patologia , Fator de Transcrição STAT3/antagonistas & inibidores , Ácidos Aminossalicílicos/farmacologia , Western Blotting , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/metabolismo , Humanos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo , Fator de Transcrição STAT3/metabolismo , Células Tumorais Cultivadas , Ensaio Tumoral de Célula-Tronco
13.
J Oncol ; 2014: 236482, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24872815

RESUMO

Objective. We investigate the prevalence of human papillomavirus (HPV) in oesophageal squamous cell carcinoma (OSCC) tissues compared to oesophageal tissue from healthy controls, in an Australian cohort. Methods. We conducted a hospital-based case-control study of 99 patients with OSCC and 100 healthy controls to examine the presence of HPV DNA. Paraffin tissues were tested using the PapType high-risk HPV detection and genotyping kit and with INNO-LiPA HPV Genotyping Extra. The biopsy samples were tested for HPV using a PCR-ELISA method based on the L1 consensus primer set PGMY09-PGMY11. Results. HPV DNA of the oncogenic genotype 16 was detected in 1/99 case specimens, a rate of 1010 per 100,000 (95% CI: 30-5500). All control specimens were negative for HPV. Significantly higher rates of smoking, other aerodigestive cancers, and mortality were seen among cases than controls. A pooled analysis of this study and the only other Australian case-control study found that 9/321 cases and 0/155 controls were positive for HPV. The pooled odds ratio for HPV being a risk factor for OSCC was 9.35 (95% CI: 0.47-190.33). Conclusion. Our results suggest that in this multifactorial cancer HPV may be an additional risk factor; although a larger, better powered study is needed.

14.
PLoS One ; 8(7): e69238, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23894436

RESUMO

BACKGROUND: The aetiological role of human papillomavirus (HPV) in oesophageal squamous cell carcinoma (OSCC) has been widely researched for more than three decades, with conflicting findings. In the absence of a large, adequately powered single case-control study, a meta-analysis of all available case-control studies is the most rigorous way of identifying any potential association between HPV and OSCC. We present the first global meta-analysis of case-control studies investigating the role of HPV in OSCC. METHODS: Case-control studies investigating OSCC tissue for presence of HPV DNA were identified. 21 case-control studies analyzing a total of 1223 cases and 1415 controls, met our inclusion criteria. HPV detection rates were tabulated for each study and all studies were assessed for quality. The random effects method was used to pool the odds ratios (OR). RESULTS: From all OSCC specimens included in this meta-analysis, 35% (426/1223) were positive for HPV DNA. The pooled OR for an HPV-OSCC association was 3.04 (95% CI 2.20 to 4.20). Meta-regression analysis did not find a significant association between OR and any of the quality domains. Influence analysis was non-significant for the effect of individual studies on the pooled estimate. Studies conducted in countries with low to medium OSCC incidence showed a stronger relationship (OR 4.65, 95% CI 2.47 to 8.76) than regions of high OSCC incidence (OR 2.65, 95% CI 1.80 to 3.91). CONCLUSIONS: Uncertainty around the aetiological role of HPV in OSCC is due largely to the small number and scale of appropriately designed studies. Our meta-analysis of these studies suggests that HPV increases the risk of OSCC three-fold. This study provides the strongest evidence to date of an HPV-OSCC association. The importance of these findings is that prophylactic vaccination could be of public health benefit in prevention of OSCC in countries with high OSCC incidence.


Assuntos
Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/virologia , Neoplasias Esofágicas/etiologia , Neoplasias Esofágicas/virologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Estudos de Casos e Controles , Carcinoma de Células Escamosas do Esôfago , Humanos
15.
Asia Pac J Clin Oncol ; 9(1): 12-28, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22897897

RESUMO

Esophageal cancer (EC) is responsible for almost half a million deaths worldwide annually and has a multifactorial etiology, which may account for its geographical variation in incidence. In the last 30 years the potential of human papillomaviruses (HPV) as oncogenes or co-factors in the tumorigenic process of esophageal squamous cell carcinoma (ESCC) has been widely studied. While the etiology of HPV in cervical and certain other anogenital and aerodigestive cancers has been established, results regarding its role in EC have been largely inconclusive. A causal association can be evaluated only with a case-control study, where normal controls are compared to ESCC cases for the presence of HPV. We reviewed all studies investigating ESCC tissue for HPV DNA and identified 139 that met our inclusion criteria, of which only 22 were case-control studies. Our results support previous findings of higher levels of HPV detection in high-risk ESCC regions than in areas of low risk. In addition, we confirm that the role of HPV in ESCC remains unclear, despite an accumulation of studies on the subject. The variations in investigative technique, study design and sample types tested may account for the lack of consistency in results. There is a need for a meta-analysis of all case-control studies to date, and for large, well-designed case-control studies with adequate power to investigate the association. The potential benefits of prophylactic HPV vaccines could be evaluated if HPV is identified as an etiological factor in EC, highlighting the need for further research in this area.


Assuntos
Carcinoma de Células Escamosas/etiologia , Neoplasias Esofágicas/etiologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/complicações , Carcinoma de Células Escamosas/epidemiologia , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/epidemiologia , Neoplasias Esofágicas/patologia , Humanos , Incidência , Infecções por Papillomavirus/virologia , Fatores de Risco
16.
Int J Oncol ; 41(4): 1181-91, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22842992

RESUMO

Signal transducer and activator of transcription 3 (STAT3) regulates many critical functions in human normal and malignant tissues, such as differentiation, proliferation, survival, angiogenesis and immune function. Constitutive activation of STAT3 is implicated in a wide range of human cancers. As such, STAT3 has been studied as a tumour therapeutic target. This review aimed principally to summarise the updated research on STAT3 inhibition studies and their therapeutic potential in solid tumours. Recent literature associated with STAT3 inhibition was reviewed through PubMed and Medline database, followed by critical comparison and analysis. Constitutive activation of STAT3 has been identified as abnormal and oncogenic. The pathway of STAT3 activation and signal transduction identifies 3 approaches for inhibition: modulating upstream positive or negative regulators, regulating RNA (DN-STAT3, anti-sense RNA, siRNA and microRNA) or targeting STAT3 protein at different domains. The last approach using small molecule STAT3 inhibitors has been the most examined so far with both preclinical and clinical studies. Targeting STAT3 using a specific inhibitor may be a useful cancer treatment approach, with the potential for a broad clinical impact.


Assuntos
Terapia de Alvo Molecular , Neoplasias/terapia , RNA Interferente Pequeno/genética , Fator de Transcrição STAT3/genética , Apoptose/genética , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/patologia , RNA Antissenso/uso terapêutico , Fator de Transcrição STAT3/antagonistas & inibidores , Fator de Transcrição STAT3/uso terapêutico , Transdução de Sinais/genética
18.
J Surg Oncol ; 104(2): 216-9, 2011 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-21472735

RESUMO

OBJECTIVE: To evaluate the distribution and scope of surgical research in Australia relating to malignant diseases in the field of surgery. METHOD: Surgical publications relating to adult malignant diseases originating from Australia were identified from a systematic literature examination using PubMed during a 12-year period between 1998 and 2009. The origin of the article, journal impact factor (IF), type of research and its subspecialty discipline were recorded. RESULTS: Over a 12-year period, 1,132 papers were published in various journals at a median annual rate of 98 papers. Four hundred eighty-five (43%) papers arose from institutions in New South Wales, 225 (20%) papers from Victoria, 150 (13%) papers from South Australia, 106 (9%) papers from Western Australia, and 77 (7%) papers from Queensland. The mean IF was 3.22 (SD = 2.5). Papers were most commonly published in journals including the ANZ Journal of Surgery (n = 237, 21%), Annals of Surgical Oncology (n = 50, 4%), British Journal of Surgery (n = 38, 3%), and Diseases of the Colon and Rectum (n = 36, 3%). The mean IF of papers published per year ranged from 2.55 to 3.87. The most number of papers were published in the fields of urological oncology (n = 103, 9%), hepatopancreaticobiliary oncology (n = 144, 13%), breast oncology (n = 174, 15%), and colorectal oncology (n = 222, 20%). CONCLUSION: Bibliometric findings of this review suggest that there is a growth in high scientific research publications in the field of surgical oncology in Australia, indicating an interest in this discipline. This research trend may impact on the national research strategy for clinical cancer control.


Assuntos
Bibliometria , Pesquisa Biomédica/tendências , Neoplasias/cirurgia , Publicações/estatística & dados numéricos , Austrália , Humanos , Publicações/tendências
20.
ANZ J Surg ; 80(12): 884-9, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21114727

RESUMO

BACKGROUND: Surgical trainees' operating theatre (OT) experiences significantly influence their ability to attain key professional competencies. A measure of trainees' satisfaction with this learning environment would allow recognition of characteristics of highly successful teaching venues and threats to trainee development. Our study aimed to validate the Surgical Theatre Educational Environment Measure (STEEM) and use it to explore Australasian surgical trainees' satisfaction with OT learning. METHODS: In a cross-sectional study, the STEEM was distributed electronically to all 1500 Royal Australasian College of Surgeons trainees in Australia and New Zealand. Trainee satisfaction was gauged using Likert-type items, an overall satisfaction measure and content analysis of free-text comments. The STEEM's psychometric properties were evaluated using exploratory factor analysis. RESULTS: Three hundred fifty-six responses were received. The STEEM's original subscales were not supported by the data; empirically grounded subscales were identified for further analysis. Most trainees were satisfied with their OT environment and satisfaction was higher in senior than junior trainees. Trainees' relationship with their supervisor correlated most strongly with overall satisfaction. Less positively, only half of trainees report discussing their operative role with their supervisor prior to surgery. CONCLUSIONS: The a priori STEEM subscales could not be replicated by factor analysis. We developed an empirically grounded instrument capable of identifying areas of trainee concern. The majority of trainees reported high levels of satisfaction. The revised instrument has potential to complement other sources of information to facilitate surgical supervisors' difficult task of optimizing trainees' compatibility with their OT learning environments.


Assuntos
Atitude do Pessoal de Saúde , Educação Baseada em Competências/organização & administração , Cirurgia Geral/educação , Salas Cirúrgicas , Satisfação Pessoal , Estudantes/psicologia , Adulto , Austrália , Competência Clínica , Estudos de Coortes , Estudos Transversais , Educação de Pós-Graduação em Medicina/organização & administração , Humanos , Pessoa de Meia-Idade , Nova Zelândia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA