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1.
BMC Oral Health ; 24(1): 729, 2024 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-38918827

RESUMO

BACKGROUND: Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and succumb to the disease; thus, there is a need for biomarkers identifying these patients for intensified treatment. Leucine-rich repeats and immunoglobulin-like domain (LRIG) protein 1 is a negative regulator of receptor tyrosine kinase signaling and a positive prognostic factor in OPSCC. Studies indicate that LRIG1 interacts with the LIM domain 7 protein (LMO7), a stabilizer of adherence junctions. Its role in OPSCC has not been studied before. METHODS: A total of 145 patients diagnosed with OPSCC were enrolled. Immunohistochemical LMO7 expression and staining intensity were evaluated in the tumors and correlated with known clinical and pathological prognostic factors, such as HPV status and LRIG1, CD44, Ki67, and p53 expression. RESULTS: Our results show that high LMO7 expression is associated with significantly longer overall survival (OS) (p = 0.044). LMO7 was a positive prognostic factor for OS in univariate analysis (HR 0.515, 95% CI: 0.267-0.994, p = 0.048) but not in multivariate analysis. The LMO7 expression correlated with LRIG1 expression (p = 0.048), consistent with previous findings. Interestingly, strong LRIG1 staining intensity was an independent negative prognostic factor in the HPV-driven group of tumors (HR 2.847, 95% Cl: 1.036-7.825, p = 0.043). CONCLUSIONS: We show for the first time that high LMO7 expression is a positive prognostic factor in OPSCC, and we propose that LMO7 should be further explored as a biomarker. In contrast to previous reports, LRIG1 expression was shown to be an independent negative prognostic factor in HPV-driven OPSCC.


Assuntos
Biomarcadores Tumorais , Carcinoma de Células Escamosas , Proteínas com Domínio LIM , Neoplasias Orofaríngeas , Humanos , Neoplasias Orofaríngeas/virologia , Neoplasias Orofaríngeas/metabolismo , Neoplasias Orofaríngeas/patologia , Neoplasias Orofaríngeas/mortalidade , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Proteínas com Domínio LIM/metabolismo , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Idoso , Fatores de Transcrição/metabolismo , Glicoproteínas de Membrana/metabolismo , Adulto , Antígeno Ki-67/metabolismo , Receptores de Hialuronatos/metabolismo , Receptores de Hialuronatos/análise , Proteína Supressora de Tumor p53/metabolismo , Infecções por Papillomavirus/complicações , Imuno-Histoquímica , Idoso de 80 Anos ou mais , Taxa de Sobrevida
2.
R I Med J (2013) ; 106(6): 20, 2023 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-37368828

Assuntos
Pupila , Humanos
3.
Acta Oncol ; 61(11): 1425-1433, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36326616

RESUMO

BACKGROUND: Ovarian carcinoma is the eighth most common cause of cancer death in women worldwide. The disease is predominantly diagnosed at a late stage. This contributes to high recurrence rates, eventually leading to the development of treatment-resistant disease. Leucine-rich repeats and immunoglobulin-like domains protein 1 (LRIG1) is a transmembrane protein that functions as a tumor suppressor and regulator of growth factor signaling. LRIG1 levels have not been investigated in human plasma previously. MATERIALS AND METHODS: A quantitative LRIG1-specific single molecule array assay was developed and validated. LRIG1 levels were quantified in plasma samples from 486 patients with suspicious ovarian masses. RESULTS: Among women with ovarian carcinoma, LRIG1 levels were significantly elevated compared to women with benign or borderline type tumors. High LRIG1 plasma levels were associated with worse overall survival and shorter disease-free survival both in the group of all malignant cases and among the stage 3 cases only. LRIG1 was an independent prognostic factor in patients with stage 3 ovarian carcinoma. CONCLUSION: LRIG1 plasma levels were elevated in patients with ovarian carcinoma, and high levels were associated with poor prognosis, suggesting that LRIG1 might be an etiologic factor and a potentially useful biomarker in ovarian carcinoma.


Assuntos
Carcinoma , Glicoproteínas de Membrana , Neoplasias Ovarianas , Feminino , Humanos , Glicoproteínas de Membrana/sangue , Neoplasias Ovarianas/diagnóstico , Prognóstico
4.
Oncol Lett ; 24(5): 393, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36276497

RESUMO

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy arising from mechanoreceptors in the basal epidermis. Due to a pronounced risk of spread and a high propensity for recurrence after treatment, immediate treatment is of utmost importance. Lambert-Eaton myasthenic syndrome (LEMS) is a paraneoplastic phenomenon affecting the muscles with autoimmune pathophysiology, and >50% of known cases are associated with an underlying malignancy. In the present report, the case of a 67-year-old man presenting with progressive proximal muscle weakness, autonomic dysfunction and involuntary weight loss is described. Symptoms and detection of voltage-gated calcium channel antibodies were consistent with LEMS. Distant metastases were found in the inguinal and iliac lymph nodes, and these were immunohistochemically confirmed to be of epithelial and neuroendocrine origin, consistent with MCC. Local radiotherapy and chemotherapy improved the symptoms; however, a change of treatment was required due to the side effects of the chemotherapy. Avelumab, an immune checkpoint inhibitor, was therefore introduced, and within a year the patient did not only experience tumor remission but also exhibited marked improvements in muscle strength and mobility. At present, 2 years later, the MCC is still in remission. To the best of our knowledge, the present report is the first to describe MCC with associated LEMS, which was successfully treated with avelumab after previous radiotherapy and chemotherapy, with both improved functional motor recovery and tumor reduction. In conclusion, the present case report demonstrated that the present treatment strategy is a potential treatment option and could thus be considered in similar cases.

5.
Mil Med ; 2022 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-35861270

RESUMO

INTRODUCTION: A commercially available snake bite device was pilot tested for novel use as a method of hemostasis and wound repair at a noncompressible site in a live swine model. The device is light, is plastic, uses a hook-and-loop strap attachment, and is easily deployed. The device could offer a method for the field repair of an actively bleeding laceration at a noncompressible site in an austere environment. MATERIALS AND METHODS: This was an interventional, prospective, controlled study in a large animal model. The study was approved by the Rhode Island Hospital Institutional Review Board (IRB) and the Animal Welfare Committee/Institutional Animal Care and Use Committee and the Lifespan Research Conflict of Interest Committee. Each animal acted as its own control. Blood loss was measured and compared between repairs of standardized incisions with and without the device's application. The lacerations were sutured closed. Two proceduralists alternated tasks of wound repair versus blood collection. Blood loss was measured by using gauze sponges to capture the blood during a 30-second free-bleeding period and during the repair itself. Using a one sample t-test (the expected difference in blood loss between the two incision repair methods = 0 if the null hypothesis were true), we calculated the mean difference in the deltas between the repair methods. RESULTS: The mean delta difference was 3.1 g (SE ± 0.97). The t-test demonstrated that there was a significantly greater blood loss during the standard repair method, t(9) = 3.11, P < 0.01 than during the repair with the device in place (see Fig. 2). A statistical power analysis conducted showed that with a sample size of 10 animals, there was sufficient statistical power to detect this significant effect (ß = 0.82, α < 0.05, one-tailed). CONCLUSIONS: There was statistically significantly less blood loss during the repairs with the device's application. This feasibility experiment demonstrates that a commercially available snakebite device may be useful for hemostasis during laceration repair at anatomic sites not amenable to application of tourniquets or compressive dressings. Strengths of the study include the prospective controlled design, including the use of each animal as its own control; alternating proceduralists to account for any variability in suturing efficiency; and the statistical significance of the results despite the small number of subjects. One weakness is that the time required for each repair was not measured. The device's portability and reusability suggest applicability in austere medical environments. Future studies could include timing the repairs, using a skin stapler or wound adhesive instead of sutures, applying a hemostatic agent before the repair, and sequentially applying the device to wounds longer than the device.

6.
Int J Gynecol Cancer ; 2022 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-35568382

RESUMO

OBJECTIVE: Both the location of primary disease and treatment side effects may have an impact on sexual function in oncogynecological patients. The aim of this study was to examine the prevalence, strategies, difficulties, and ideas for improvement in sexual counseling among specialists managing patients with gynecologic malignancies. METHODS: This was a cross-sectional survey study performed among healthcare professionals treating patients with gynecologic malignancies. A self-prepared questionnaire included 61 questions concerning general demographic information and different aspects of sexual counseling in the gynecologic oncology practice. Analysis included attitudes, behaviors, management strategies, difficulties, and ideas for possible systemic improvements. Statistical analysis involved descriptive statistics, two-sided chi-square test, and Fisher's exact test. RESULTS: A total of 150 respondents from 46 countries answered the survey. The majority of survey participants stated that sexual counseling of oncological patients is very important (n=73, 49%) or important (n=46, 31%). One hundred and two (68%) respondents agreed that sexual counseling of gynecologic oncology patients should be routinely provided by the specialist managing the primary disease. However, collecting information concerning sexual function is performed often or always by only 21% of respondents and 19% discuss the topic rarely or never. The most frequently indicated barriers leading to difficulties in sexual counseling include lack of time (74%), lack of specialist knowledge (55%), and patient embarrassment (48%). One hundred and seven (71%) respondents expressed interest in participating in sexual counseling workshops organized by the European Society of Gynaecological Oncology (ESGO)/European Network of Young Gynaecological Oncologists (ENYGO), 74 (49%) would like to access webinars on the topic, and 120 (80%) would be interested in materials in the ESGO online educational resources. CONCLUSION: One of the proposed solutions to insufficient access to sexual care for women with gynecologic malignancies is providing access to specialist educational programs for both patients and healthcare specialists.

7.
Int J Med Educ ; 12: 233-242, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34842177

RESUMO

OBJECTIVES: We aimed to explore learning experiences among medical students learning to perform pelvic examinations and to identify factors that facilitate their training. METHODS: A mixed-methods study including a web-based survey and focus group discussions (FGDs) was conducted among medical students who had completed their obstetrics and gynaecology (ObGyn) clerkship. The FGDs were recorded, transcribed and analysed using qualitative content analysis with systematic text condensation. Survey factors were compared using the χ2 test or Fisher's exact test. RESULTS: 160 students (97 female, 61 male, two other) at six universities in Sweden responded to the survey. Two mixed FGDs were conducted. The majority (87%) of the students experienced confidence in performing pelvic examinations, stating that sufficient, repeated training opportunities and support from a clinical tutor were crucial components of the learning experience. Prior to the ObGyn clerkship, negative expectations were more common among male students. The male participants experienced having a disadvantage because of their gender, while female students considered their gender an advantage (p<0.001, N=121, Fisher's Exact Test). The clinical tutor and the use of professional patients (PPs) had a fundamental role in providing learning opportunities by including the student in patient care activities. CONCLUSIONS: The importance of the clinical tutor, as well as the use of PPs, are important factors when planning education in pelvic examinations, and this knowledge could be used when educating other intimate examinations during medical school. In addition, similar investigations on students' experience in training other intimate examinations could be considered.


Assuntos
Estágio Clínico , Ginecologia , Obstetrícia , Estudantes de Medicina , Feminino , Exame Ginecológico , Ginecologia/educação , Humanos , Masculino , Obstetrícia/educação , Gravidez
8.
Acta Oncol ; 60(9): 1218-1224, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34156893

RESUMO

INTRODUCTION: Endometrioid endometrial carcinoma is a cancer type with generally excellent prognosis when diagnosed at an early stage, but there is a subset of patients with relapsing disease in spite of early diagnosis and surgical treatment. There is a need to find prognostic markers to identify these patients with increased risk of relapse. Depth of myometrial invasion, histological grade, and presence of lymphovascular invasion are known risk factors. DNA content (ploidy) and proliferation measured as S-phase fraction (SPF) have been discussed as prognostic markers but need additional evaluation. MATERIAL AND METHODS: We evaluated relapse-free survival (RFS) with respect to ploidy and SPF, which was analyzed by flow cytometry on fresh tumor tissue, in a cohort of 1001 women treated for stage I endometrioid endometrial carcinoma in northern Sweden during the period of 1993-2010, with a median follow up time of 12.0 years. Data were obtained from historical records. RESULTS: In simple analysis, both aneuploidy and high SPF were associated to increased risk of relapse with hazard ratios (HR) 2.37 (95% CI 1.52-3.70) and 1.94 (95% CI 1.24-3.02), respectively. Our data also confirmed stage, tumor grade, and ploidy as independent prognostic markers in an age adjusted cox regression multivariable analysis but we did not find SPF to contribute to prognosis. However, the combination of aneuploidy and high SPF identified a group of patients with increased risk of relapse, HR 2.02 (95% CI 1.19-3.44). CONCLUSION: In this study, which is the largest study of ploidy and SPF in stage I endometrioid endometrial carcinoma using fresh frozen tissue, aneuploidy was shown to be an independent prognostic marker. Furthermore, the combination of aneuploidy and high SPF could be used to identify patients with increased risk of relapse.


Assuntos
DNA de Neoplasias , Neoplasias do Endométrio , Aneuploidia , Neoplasias do Endométrio/genética , Feminino , Citometria de Fluxo , Humanos , Recidiva Local de Neoplasia/genética , Prognóstico , Fase S
9.
Cancers (Basel) ; 13(6)2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33802837

RESUMO

Endometrial cancer (EC) is the most common gynecologic malignancy in Sweden and it has various prognostic factors. The LRIG family is a group of three integral surface proteins with a similar domain organization. The study aimed to explore LRIG family as prognostic factor proteins in EC. The initial study cohort included 100 women with EC who were treated at the Department of Women's and Children's Health, Karolinska University Hospital Solna, between 2007 and 2012. We assessed the associations between LRIG protein expression and type, grade, and stage of EC, as well as progression-free and overall survival. Immunohistochemistry results revealed that most women in the analytical sample had >50% LRIG1-, LRIG2- and LRIG3-positive cells. A statistically significant association was observed between having a high number of LRIG3-positive cells and superior overall survival (incidence rate ratio = 0.977; 95% confidence interval: 0.958-0.996, p = 0.019). Moreover, positive LRIG3 staining of the cell membrane was associated with reducing in the risk of death (hazard ratio = 0.23; 95% confidence interval: 0.09-0.57). Our results show that LRIG3 expression might be a prognostic factor in EC. The role of LRIG1 and LRIG2 expression remains to be further investigated.

11.
Int J Cancer ; 149(1): 66-74, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33634882

RESUMO

To explore the largely unknown etiology of small intestine cancer, we examined metabolic factors and risk of small intestine cancer overall and by subtypes. Among 404 220 women and 403 265 men in six European cohorts, we applied Cox regression with adjustment for smoking and body mass index (BMI), to calculate sex-specific hazard ratios (HRs) of small intestine cancer by levels of BMI, mean arterial pressure (MAP) and plasma total cholesterol, triglycerides and glucose. We also calculated HRs for these factors combined (metabolic score; MetS) and used Wald test statistics to investigate pairwise interactions between metabolic factors on risk. We also performed analyses separately per subtype (neuroendocrine tumors [NETs] and adenocarcinomas). During a median follow-up of 16.9 years, 144 women and 195 men were diagnosed with small intestine cancer, including 184 NETs and 99 adenocarcinomas. Among men, no main associations or interactions between metabolic factors were observed in relation to the risk of small intestine cancer. Among women, triglycerides were positively and linearly associated with risk (HR per standard deviation [SD]: 1.23, 95% confidence interval [CI]: 1.04-1.46), and a positive association was also observed for the MetS (HR per SD: 1.25, 95% CI: 1.02-1.52). Positive interactions were observed among women between triglycerides and cholesterol (P = .0005), and between MAP and glucose (P = .009), on risk. Glucose was positively associated with adenocarcinomas among women. This large, prospective study suggests that elevated triglycerides, and metabolic factors in interaction, confer an increased risk of small intestine cancer among women, but not among men.


Assuntos
Adenocarcinoma/patologia , Biomarcadores/análise , Neoplasias Intestinais/patologia , Intestino Delgado/patologia , Síndrome Metabólica/complicações , Adenocarcinoma/epidemiologia , Adenocarcinoma/etiologia , Adulto , Pressão Sanguínea , Índice de Massa Corporal , Europa (Continente)/epidemiologia , Feminino , Seguimentos , Humanos , Neoplasias Intestinais/epidemiologia , Neoplasias Intestinais/etiologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco
12.
Artigo em Inglês | MEDLINE | ID: mdl-32958506

RESUMO

INTRODUCTION: Palliative care is an important aspect of gynaecological oncology practice. In order to successfully integrate end-of-life (EOL) care in the disease trajectory, it is crucial to incorporate systematic training in subspecialty programmes in gynaecological oncology. We aimed to evaluate the quality of training in palliative care across gynaecological oncology fellows in Europe and to provide a framework to facilitate learning opportunities. METHODS: A web-based questionnaire was sent to members of the European Network of Young Gynae-Oncologists (ENYGO). The survey consisted of 36 items covering six domains: respondents' characteristics, quality and quantity of teaching, curriculum achievements, observation and feedback, EOL clinical practice and attitudes about palliative care. RESULTS: Of the 703 clinicians enrolled in the study, 142 responded (20.2%). Although the majority worked in university hospitals, only half of them (47%) were in a formal subspecialty programme. The majority of respondents (60%) were trained without a mandatory rotation in palliative care units and considered the quality of EOL care teaching as 'very poor' or 'poor' (57.7%). The majority of respondents (71.6%) did not receive any supervision or feedback at the time of their first consultation on changing the goals of care. CONCLUSION: Our study underlines lack of structured teaching and supervision in palliative care contents among European fellows in gynaecological oncology. Broad education of healthcare providers is a key factor to achieve the integration of palliative care in gynaecological oncology practice. Stakeholders like European Society of Gynaecological Oncology/ENYGO play an important role to facilitate educational activities and training programmes targeting to EOL care.

13.
Oncol Rep ; 42(1): 142-150, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31059071

RESUMO

The present study was conducted to investigate the possible prognostic value of molecular markers LRIG1­2 and LIM domain 7 protein (LMO7) in vulvar squamous cell carcinoma (VSCC) and their possible correlation to human papilloma virus (HPV)­ and p16INK4a­status of the tumors. Patients diagnosed with VSCC at the University Hospital of Umeå, Sweden, during the years 1990­2013 were selected. Tumor blocks were retrieved from tissue archives and clinical data were collected from the records of patients. HPV­PCR analysis, HPV genotyping and immunohistochemistry were performed. In total, 112 patients were included. Forty percent of the tumors were HPV­positive, 27% were p16INK4a­positive and 23% were positive for both HPV and p16INK4a (considered HPV­driven). HPV­positivity and p16INK4a­positivity were associated with prolonged disease­free survival (DFS) in Kaplan­Meier survival analysis. Leucine­rich repeats and immunoglobulin­like domains 1 (LRIG1) immunoreactivity was not significantly associated with survival. High leucine­rich repeats and immunoglobulin­like domains 2 (LRIG2) immunoreactivity was associated with a prolonged overall survival (OS) (P=0.001). By analyzing HPV­negative cases only, it was determined that high LRIG2 immunoreactivity was associated with both favorable OS (P=0.008) and DFS (P=0.031). LRIG2 immunoreactivity was also an independent prognostic factor in multivariate analysis of OS (P=0.002, HR=0.41; 95% CI, 0.24­0.71). High immunoreactivity with LMO7­1250 antibody was associated with survival benefits in the whole cohort (OS; P=0.011) although DFS was only prolonged in HPV­negative and not HPV­driven tumors (P=0.038 and 0.042, respectively). The present study indicated that LRIG2 and LMO7 may be useful prognostic markers in VSCC, particularly for patients without HPV­driven tumors or with advanced tumors at diagnosis. In contrast to earlier observations regarding other types of squamous cell carcinoma, LRIG1 was not a significant prognostic factor in VSCC.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Proteínas com Domínio LIM/metabolismo , Glicoproteínas de Membrana/metabolismo , Papillomaviridae/genética , Infecções por Papillomavirus/metabolismo , Fatores de Transcrição/metabolismo , Neoplasias Vulvares/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/virologia , DNA Viral/genética , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/virologia , Prognóstico , Análise de Sobrevida , Neoplasias Vulvares/virologia
15.
Mol Cell Proteomics ; 18(4): 735-743, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30692274

RESUMO

Human papillomavirus (HPV) is recommended as the primary test in cervical cancer screening, with co-testing by cytology for HPV-positive women to identify cervical lesions. Cytology has low sensitivity and there is a need to identify biomarkers that could identify dysplasia that are likely to progress to cancer. We searched for plasma proteins that could identify women with cervical cancer using the multiplex proximity extension assay (PEA). The abundance of 100 proteins were measured in plasma collected at the time of diagnosis of patients with invasive cervical cancer and in population controls using the Olink Multiplex panels CVD II, INF I, and ONC II. Eighty proteins showed increased levels in cases compared with controls. We identified a signature of 11 proteins (PTX3, ITGB1BP2, AXIN1, STAMPB, SRC, SIRT2, 4E-BP1, PAPPA, HB-EGF, NEMO and IL27) that distinguished cases and controls with a sensitivity of 0.96 at a specificity of 1.0. This signature was evaluated in a prospective replication cohort with samples collected before, at or after diagnosis and achieved a sensitivity of 0.78 and a specificity 0.56 separating samples collected at the time of diagnosis of invasive cancer from samples collected prior to diagnosis. No difference in abundance was seen between samples collected prior to diagnosis or after treatment as compared with population controls, indicating that this protein signature is mainly informative close to time of diagnosis. Further studies are needed to determine the optimal window in time prior to diagnosis for these biomarker candidates.


Assuntos
Bioensaio/métodos , Biomarcadores Tumorais/sangue , Proteínas Sanguíneas/metabolismo , Neoplasias do Colo do Útero/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Variação Genética , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Curva ROC , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/terapia , Adulto Jovem
16.
Carcinogenesis ; 40(2): 269-278, 2019 04 29.
Artigo em Inglês | MEDLINE | ID: mdl-30596972

RESUMO

Invasive cervical cancer (ICC) with very low titer of high-risk human papillomavirus (HPV) has worse clinical outcome than cases with high titer, indicating a difference in molecular etiology. Fresh-frozen ICC tumors (n = 49) were classified into high- and low-HPV-titer cases using real-time PCR-based HPV genotyping. The mutation spectra were studied using the AmpliSeq Comprehensive Cancer Panel and the expression profiles using total RNA sequencing, and the results were validated using the AmpliSeq Transcriptome assay. HPV DNA genotyping and RNA sequencing showed that 16.6% of ICC tumors contained very low levels of HPV DNA and HPV transcripts. Tumors with low HPV levels had more mutations with a high allele frequency and fewer mutations with low allele frequency relative to tumors with high HPV titer. A number of genes showed significant expression differences between HPV titer groups, including genes with somatic mutations. Gene ontology and pathway analyses implicated the enrichment of genes involved in DNA replication, cell cycle control and extracellular matrix in tumors with low HPV titer. The results indicate that in low titer tumors, HPVs act as trigger of cancer development whereas somatic mutations are clonally selected and become drivers of the tumor development process. In contrast, in tumors with high HPV titer the expression of HPV oncoproteins plays a major role in tumor development and the many low frequency somatic mutations represent passengers. This putative subdivision of invasive cervical tumors may explain the higher radiosensitivity of ICC tumors with high HPV titer and thereby have consequences for clinical management.


Assuntos
Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Neoplasias do Colo do Útero/etiologia , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/virologia , DNA Viral/genética , Feminino , Humanos , Pessoa de Meia-Idade , Mutação/genética , Papillomaviridae/genética , Análise de Sequência de RNA/métodos
17.
Int J Oncol ; 52(4): 1189-1197, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29436694

RESUMO

Papillary thyroid carcinoma (PTC) and medullary thyroid carcinoma (MTC) are characterized by genomic rearrangements and point mutations in the proto-oncogene RET. Leucine-rich repeats and immunoglobulin-like domains 1 (LRIG1) is a suppressor of various receptor tyrosine kinases, including RET. LRIG1 expression levels are associated with patient survival in many cancer types. In the present study, we investigated whether the oncogenic RET mutants RET2A (C634R) and RET2B (M918T) were regulated by LRIG1, and the possible effects of LRIG1 expression in thyroid cancer were investigated in three different clinical cohorts and in a RET2B-driven mouse model of MTC. LRIG1 was shown to physically interact with both RET2A and RET2B and to restrict their ligand-independent activation. LRIG1 mRNA levels were downregulated in PTC and MTC compared to normal thyroid gland tissue. There was no apparent association between LRIG1 RNA or protein expression levels and patient survival in the studied cohorts. The transgenic RET2B mice developed pre-cancerous medullary thyroid lesions at a high frequency (36%); however, no overt cancers were observed. There was no significant difference in the incidence of pre-cancerous lesions between Lrig1 wild-type and Lrig1-deficient RET2B mice. In conclusion, the findings that LRIG1 is a negative regulator of RET2A and RET2B and is also downregulated in PTC and MTC may suggest that LRIG1 functions as a thyroid tumor suppressor.


Assuntos
Carcinoma Neuroendócrino/genética , Carcinoma Papilar/genética , Regulação Neoplásica da Expressão Gênica/genética , Glicoproteínas de Membrana/genética , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/genética , Animais , Carcinoma Neuroendócrino/metabolismo , Carcinoma Papilar/metabolismo , Regulação para Baixo , Humanos , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Proto-Oncogene Mas , Proteínas Proto-Oncogênicas c-ret/metabolismo , Câncer Papilífero da Tireoide , Neoplasias da Glândula Tireoide/metabolismo
18.
Anticancer Res ; 37(10): 5319-5328, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28982840

RESUMO

Human papillomavirus (HPV)-positive tonsillar- and base of tongue cancer is increasing epidemically and has much better outcome than corresponding HPV-negative cancer and most other head and neck cancers with around 80% 3-year disease free survival with conventional radiotherapy and surgery. Consequently, most HPV-positive cancer patients may not require the intensified chemoradiotherapy given to many head and neck cancer patients and would, with tapered treatment, avoid several severe side-effects. Moreover, intensified therapy has not improved survival and treatment alternatives are needed. To identify patients eligible for tapered or targeted therapy, additional biomarkers are required. Several studies have, therefore, focused on finding predictive markers, some of which are also potentially targetable. To conclude, better-tailored therapy, either as tapered or targeted, is important for increasing numbers of patients with HPV-positive tonsillar- and base of tongue cancer. This review deals with some of these issues and presents some promising markers.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/metabolismo , Papillomaviridae/isolamento & purificação , Infecções por Papillomavirus/complicações , Neoplasias da Língua/metabolismo , Neoplasias Tonsilares/metabolismo , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/virologia , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/virologia , Testes de DNA para Papilomavírus Humano , Humanos , Estadiamento de Neoplasias , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/virologia , Papillomaviridae/classificação , Papillomaviridae/genética , Infecções por Papillomavirus/terapia , Infecções por Papillomavirus/virologia , Seleção de Pacientes , Valor Preditivo dos Testes , Carcinoma de Células Escamosas de Cabeça e Pescoço , Neoplasias da Língua/genética , Neoplasias da Língua/terapia , Neoplasias da Língua/virologia , Neoplasias Tonsilares/genética , Neoplasias Tonsilares/terapia , Neoplasias Tonsilares/virologia , Resultado do Tratamento
19.
PLoS One ; 12(8): e0183816, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28841699

RESUMO

BACKGROUND: Primary vaginal carcinoma (PVC) is a rare malignancy. Established prognostic factors include tumour stage and age at diagnosis. The leucine-rich repeats and immunoglobuline-like domains (LRIG)-1 protein functions as a tumour suppressor, but less is known about the functions of LRIG2 and LRIG3. The present study aimed to evaluate the expression of LRIG proteins and analyse their possible associations with clinical characteristics and survival in a cohort of PVC patients. METHODS: We used immunohistochemistry to investigate LRIG1, LRIG2, and LRIG3 expression in tumour samples from a consecutive cohort of 70 PVC patients. The association between LRIG protein expression and clinical characteristics and cancer-specific survival was investigated using univariate and multivariate analyses. RESULTS: The majority of PVC patients (72%) had >50% LRIG1- and LRIG2-positive cells, and no or low LRIG3-positive cells. HPV status was significantly correlated with LRIG1 expression (p = 0.0047). Having high LRIG1 expression was significantly correlated with superior cancer-specific survival in univariate and multivariate analyses. LRIG2 and LRIG3 expression did not significantly correlate with clinical characteristics or survival. CONCLUSION: LRIG1 expression might be of interest as a prognostic marker in PVC patients, whereas the role of LRIG2 and LRIG3 expression remains to be clarified.


Assuntos
Glicoproteínas de Membrana/metabolismo , Neoplasias Vaginais/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Prognóstico
20.
Int J Gynecol Cancer ; 27(3): 620-626, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28187096

RESUMO

OBJECTIVE: The aim of the study was to assess patterns in the use of social media (SM) platforms and to identify the training needs among European gynecologic oncology trainees. METHODS: In 2014, a web-based survey was sent to 633 trainees from the European Network of Young Gynaecological Oncologists (ENYGO) database. The 14-item questionnaire (partially using a 1- to 5-point Likert scale) assessed respondents' use of SM and preference for workshop content and organization. Descriptive analysis was used to describe the mean scores reported for different items, and the internal reliability of the questionnaire was assessed by Cronbach α. RESULTS: In total, 170 ENYGO members (27%) responded to the survey. Of those, 91% said that they use SM platforms, mostly for private purposes. Twenty-three percent used SM professionally and 43% indicated that they would consider SM to be a clinical discussion forum. The respondents said that they would like updates on conferences and professional activities to be shared on SM platforms. Complication management, surgical anatomy, and state of the art in gynecologic oncology were identified as preferred workshops topics. The most frequently indicated hands-on workshops were laparoscopic techniques and surgical anatomy. Consultants attached a higher level of importance to palliative care education and communication training than trainees. The mean duration of the workshop preferred was 2 days. CONCLUSIONS: This report highlights the significance of ENYGO trainees' attachment to SM platforms. Most respondents expect ENYGO to use these online channels for promoting educational activities and other updates. Using SM for clinical discussion will require specific guidelines to secure professional and also consumer integrity. This survey confirms surgical management and the state of the art as important knowledge gaps, and ENYGO has tailored its activities according to these results. Future activities will further direct attention and resources to education in palliative care and molecular tumor biology.


Assuntos
Comunicação , Ginecologia/educação , Oncologia/educação , Mídias Sociais , Adulto , Educação Médica Continuada/métodos , Feminino , Humanos , Inquéritos e Questionários
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