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1.
Clin Oncol (R Coll Radiol) ; 35(11): 744-755, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37679230

RESUMO

AIMS: The role of metformin on the radiosensitising effect of cisplatin is not clear. Here we investigated the radiosensitising effect of metformin alone and combined with cisplatin in HeLa cells, as well as the implications of the adenosine monophosphate-activated protein kinase (AMPK) pathway on the radiosensitising effect. MATERIALS AND METHODS: HeLa cells were treated with ionising radiation, metformin, cisplatin, A769662 (AMPK activator) and dorsomorphin (AMPK inhibitor) or in combination. A cell proliferation assay, Western blot and flow cytometry were carried out. RESULTS: Metformin potentiated cisplatin cytotoxicity when administered 4 h before ionising radiation. Although the radiosensitising effects of metformin and cisplatin alone were observed, which is more apparent at high ionising radiation doses, the metformin-cisplatin combination did not increase the radiosensitivity of cisplatin at any ionising radiation dose. Dorsomorphin alone significantly decreased cell proliferation and potentiated the radiosensitising effects of cisplatin with ionising radiation. Administration of A769662 24 h prior to cisplatin treatment resulted in an increased AMPK level that yielded resistance to cisplatin, but this effect was not observed in HeLa cells concomitantly treated with A769662 and cisplatin. CONCLUSIONS: Modulation of AMPK may have a role in cervical cancer treatment. Increased AMPK levels result in higher sensitivity to ionising radiation but causes resistance to cisplatin. Dorsomorphin is proven to be a potent radiosensitising agent. The use of metformin alone may be an option as a radiosensitiser during high-dose ionising radiation (e.g. intracavitary brachytherapy).


Assuntos
Neoplasias Pulmonares , Metformina , Neoplasias do Colo do Útero , Feminino , Humanos , Cisplatino/farmacologia , Metformina/farmacologia , Metformina/uso terapêutico , Proteínas Quinases Ativadas por AMP/metabolismo , Proteínas Quinases Ativadas por AMP/farmacologia , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Células HeLa , Apoptose , Neoplasias Pulmonares/radioterapia , Quimiorradioterapia , Linhagem Celular Tumoral
2.
Eur J Obstet Gynecol Reprod Biol ; 256: 57-62, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33171418

RESUMO

This European consensus statement on essential colposcopy provides standards for the general colposcopist seeing women referred for colposcopy with an abnormal cervical screening test (including cytology and HPV tests) or with a clinically suspicious cervix. The article gives guidance regarding the aims and conduct of colposcopy. Recommendations are provided on colposcopy technique, the management of common colposcopy issues, treatment and follow-up of after treatment of CIN or early stage cervical. Colposcopists should make an informed decision on the management of each individual that is referred and organize appropriate follow-up. Cervical cancer is still a major health issue and the quality of care can only improve if there is a structured guidance for women with an abnormal smear or suspicious cervix.


Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Neoplasias do Colo do Útero , Colposcopia , Consenso , Detecção Precoce de Câncer , Feminino , Humanos , Papillomaviridae , Infecções por Papillomavirus/diagnóstico , Gravidez , Neoplasias do Colo do Útero/diagnóstico , Esfregaço Vaginal , Displasia do Colo do Útero/diagnóstico
3.
Cancer Radiother ; 23(8): 853-859, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31640927

RESUMO

PURPOSE: To evaluate the efficacy and toxicity of hypofractionated radiotherapy in non-metastatic soft tissue and bone sarcomas. PATIENTS AND METHODS: Thirty patients underwent hypofractionated radiotherapy between 2007 and 2015. Overall, 17 patients underwent primary hypofractionated radiotherapy, nine underwent hypofractionated radiotherapy for reirradiation, and four received a boost dose via hypofractionated radiotherapy after external beam radiotherapy. Most common disease sites were head and neck and retroperitoneum. Hypofractionated radiotherapy was administered with a definitive, adjuvant, or neoadjuvant intent. RESULTS: Median age was 37 years (range: 11-82 years). Median hypofractionated radiotherapy dose was 35Gy (range: 20-50Gy) in three to five fractions. Median follow-up was 21 months (range: 1-108 months). One- and 2-year overall survival rate was 75% and 52%, respectively. One- and 2-year local recurrence-free survival rate was 59% and 48%, with local recurrence rates of 16% and 33% in 1 and 2 years, respectively. Univariate analysis revealed tumour size (P=0.04), hypofractionated radiotherapy intent (P=0.016) and reirradiation (P=0.001) as prognostic factors for local recurrence-free survival. Severe late toxicity was observed in one patient as grade 3 trismus. CONCLUSION: Hypofractionated radiotherapy as the primary treatment or for reirradiation has been shown to be safe in the treatment of bone and soft tissue sarcomas. It can provide relatively good local control and survival rates.


Assuntos
Neoplasias Ósseas/radioterapia , Hipofracionamento da Dose de Radiação , Sarcoma/radioterapia , Neoplasias de Tecidos Moles/radioterapia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Ósseas/mortalidade , Neoplasias Ósseas/patologia , Criança , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Radioterapia Adjuvante/métodos , Reirradiação/métodos , Sarcoma/mortalidade , Sarcoma/patologia , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/patologia , Taxa de Sobrevida , Carga Tumoral , Adulto Jovem
4.
Hum Exp Toxicol ; 36(11): 1121-1130, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27932539

RESUMO

There are limited data regarding effect of trastuzumab on radiation-induced cardiovascular toxicity when used sequentially or concomitantly. This experimental study aims to investigate effect of trastuzumab on radiation-induced cardiovascular toxicity with respect to the treatment sequence. One hundred and eight female Wistar albino rats were divided into six groups (G): G1 was control, G2 was trastuzumab, and G3 was radiotherapy (RT); G4 and G6 were sequential RT and trastuzumab; and G5 was concomitant RT and trastuzumab groups, respectively. Rats were killed at 6th h, 21st and 70th days after RT; thoracic aorta and heart samples were obtained. Transthoracic echocardiography and functional studies evaluating relaxation of thoracic aorta were performed. Subendothelial edema scores of thoracic aorta samples at 21st and 70th days were higher in RT groups (G3, G4, G5, and G6) ( p < 0.001). There was a deterioration of relaxation responses of thoracic aorta samples in RT groups ( p < 0.001). Cardiac fibrosis (CF) scores revealed detrimental effect of RT beginning from 6th h and trastuzumab from 21st day. RT groups showed further deterioration of CF at 70th day. Ejection fraction, left ventricular mass, and fractional shortening were significantly decreased in G4, G5, and G6. Trastuzumab may increase pathological damage in cardiovascular structures when used with RT regardless of timing.


Assuntos
Antineoplásicos Imunológicos/farmacologia , Cardiopatias/etiologia , Coração/efeitos da radiação , Lesões por Radiação/tratamento farmacológico , Trastuzumab/farmacologia , Animais , Antineoplásicos Imunológicos/administração & dosagem , Esquema de Medicação , Feminino , Ratos , Ratos Wistar , Volume Sistólico/efeitos da radiação , Trastuzumab/administração & dosagem
5.
Connect Tissue Res ; 57(5): 360-73, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27191749

RESUMO

INTRODUCTION: This study aims to histopathologically, biomechanically, and immunohistochemically compare the fourth-week efficiencies of local platelet-rich plasma (PRP) and bone marrow-derived mesenchymal stem cell (rBM-MSC) treatments of the Achilles tendon ruptures created surgically in rats. MATERIALS AND METHODS: The study included 35 12-month-old male Sprague Dawley rats, with an average weight of 400-500 g. Five rats were used as donors for MSC and PRP, and 30 rats were separated into MSC, PRP, and control groups (n = 10). The Achilles tendons of the rats were cut transversely, the MSC from bone marrow was administered to the MSC group, the PRP group received PRP, and the control group received physiological saline to create the same surgical effect. In previous studies, it was shown that this physiological saline does not have any effect on tendon recovery. Thirty days after the treatment, the rats were sacrificed and their Achilles tendons were examined histopathologically, immunohistochemically, and biomechanically. RESULTS: The use of rBM-MSC and PRP in the Achilles tendon ruptures when the tendon is in its weakest phase positively affected the recovery of the tendon in histopathologic, immunohistochemical, and biomechanical manners compared to the control group (p < 0.05). While the levels of pro-inflammatory cytokines TNF-α, IFNγ, and IL 1ß were significantly low, the levels of anti-inflammatory cytokines and growth factors playing key roles in tendon recovery, such as IL2, VEGF, transforming growth factor-beta, and HGF, were significantly higher in the MSC group than those of the PRP and control groups (p < 0.05). In the MSC group, the [Formula: see text] (mm) value was significantly higher (p ˂ 0.05) than that in the PRP and control groups. CONCLUSION: rBM-MSC and PRP promote the recovery of the tendon and increase its structural strength. The use of PRP and MSC provides hope for the treatment of the Achilles tendon ruptures that limit human beings' functionalities and quality of life, particularly for athletes. It is thought that the use of MSC can be more effective for tendon healing; hence, more extensive and advanced studies are needed on this topic.


Assuntos
Tendão do Calcâneo/lesões , Tendão do Calcâneo/patologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Plasma Rico em Plaquetas/metabolismo , Traumatismos dos Tendões/patologia , Traumatismos dos Tendões/terapia , Tendão do Calcâneo/efeitos dos fármacos , Tendão do Calcâneo/fisiopatologia , Animais , Fenômenos Biomecânicos , Células da Medula Óssea/citologia , Citocinas/metabolismo , Masculino , Inclusão em Parafina , Ratos Sprague-Dawley , Ruptura , Traumatismos dos Tendões/fisiopatologia , Resistência à Tração
6.
Technol Cancer Res Treat ; 15(1): 203-11, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25687510

RESUMO

BACKGROUND: The aim of this study was to evaluate the efficacy and toxicity of robotic CyberKnife (Accuray Incorporated, Sunnyvale, California)-based stereotactic body radiation therapy (SBRT) in patients with recurrent or metastatic abdominopelvic tumors. METHODS AND MATERIALS: A total of 69 patients treated between May 2008 and January 2011 were evaluated retrospectively. Indication for SBRT was persistent disease in 3 (4%) patients, local recurrence in 29 (42%) patients, regional recurrence in 13 (19%) patients, and oligometastatic disease in 24 (35%) patients. Forty-two (61%) patients were previously irradiated to the same region and 27 (39%) patients were treated for the first time. The median age was 59 years (range, 24-86 years). There were 31 (45%) male and 38 (55%) female patients. The median total dose was 30 Gy (range, 15-60 Gy) delivered with a median 3 fractions (range, 2-5 fractions). The tumor response to treatment was assessed by computed tomography, magnetic resonance imaging, or positron emission tomography. RESULTS: At the 12-month (range, 2-44 months) median follow-up, local control was 65% and median overall survival (OS) was 20 months. A larger gross tumor volume (≥ 67 cm(3)) was significantly correlated with worse 1-year OS (81% vs 48%, P = .03). The patients with local recurrence occurring <11 months had a significantly shorter 1-year local control rate than patients with ≥ 11 months (31% vs 91%, P < .001). Grade 3-4 acute and late toxicities were seen in 7% and 15% of patients, respectively. The patients with previous radiotherapy history had significantly higher rate of acute toxicity (19% vs 0%, P = .019). Late toxicity was significantly higher in pelvic tumors than in abdominal tumors (3% vs 28%, P = .004). CONCLUSION: The SBRT seems to be feasible and resulted in good treatment outcomes in patients with recurrent or metastatic abdominopelvic tumors.


Assuntos
Neoplasias Abdominais/cirurgia , Recidiva Local de Neoplasia/cirurgia , Neoplasias Pélvicas/cirurgia , Radiocirurgia , Neoplasias Abdominais/mortalidade , Neoplasias Abdominais/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Robótica , Cirurgia Assistida por Computador , Resultado do Tratamento , Adulto Jovem
7.
J Plant Physiol ; 171(10): 807-16, 2014 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-24877672

RESUMO

Cyclitols were prepared from corresponding allylic hydroperoxides, synthesized by photooxygenation of the appropriate cyclic alkenes. These hydroperoxides were then separately treated with a catalytic amount of OsO4. Synthesized dl-cyclopentane-1,2,3-triol 9 (A), dl-cyclohexane-1,2,3-triol 12 (B), and dl-cycloheptane-1,2,3-triol 15 (C) were used in the investigation of plant stress. Antioxidants, lipid peroxidation, and water status of chickpea species exposed to synthetic cyclitols under water deficit were examined. Cyclitol derivatives significantly decreased leaf water potential, lipid peroxidation and H2O2 levels of wild and cultivated species under water deficit. Cyclitol treatments affected antioxidant enzyme activities differently in both species under water deficit. The highest SOD activity was found in A10-treated Cicer arietinum (cultivar) and C10-treated Cicer reticulatum (wild type) under water deficit. CAT activity increased in C. arietinum exposed to A cyclitols, while it increased slightly and then decreased in cyclitol-treated C. reticulatum under stress conditions. AP and GR activities were significantly increased in C. arietinum under water deficit. AP activity increased in C derivatives-treated C. arietinum, while it remained unchanged in C. reticulatum on day 1 of water deficit. GR activity was increased in A derivaties-treated C. arietinum and C derivatives-treated C. reticulatum on day 1 of water deficit and decreased with severity of stress (except for B10-treated C. arietinum). The level of AsA in C treatments and GSH in A treatments increased in C. arietinum on day 1 of water deficit, while in C. reticulatum, AsA and GSH levels decreased under stress conditions. We conclude that exogenous synthetic cyclitol derivatives are biologically active and noncytotoxic, resulting in higher antioxidant activities and lower water potential, thus increasing the water deficit tolerance of chickpea under water deficit, especially of cultivated chickpea. We also propose that synthetic cyclitol derivatives can reduce reactive oxygen species and membrane damage and are beneficial for stress adaptation.


Assuntos
Cicer/efeitos dos fármacos , Ciclitóis/farmacologia , Regulação Enzimológica da Expressão Gênica , Água/fisiologia , Antioxidantes/metabolismo , Ascorbato Peroxidases/metabolismo , Ácido Ascórbico/metabolismo , Catalase/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Cicer/enzimologia , Cicer/fisiologia , Ciclitóis/síntese química , Ciclitóis/química , Desidratação , Regulação da Expressão Gênica de Plantas , Glutationa/metabolismo , Glutationa Redutase/metabolismo , Peróxido de Hidrogênio/metabolismo , Peroxidação de Lipídeos , Estresse Oxidativo , Reguladores de Crescimento de Plantas/metabolismo , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo
8.
Technol Cancer Res Treat ; 13(1): 11-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23819495

RESUMO

Chordomas are uncommon neoplasms and there is still controversy regarding establishment of diagnosis and management. The aim of this study was to evaluate efficacy and toxicity of fractionated stereotactic radiosurgery (FSRS) in skull base chordomas. There were 4 female (36%) and 7 male (64%) patients. FSRS was delivered with CyberKnife (Accuray Inc., Sunnyvale, CA). The median tumor volume was 14.7 cc (range, 3.9-40.5 cc). The median marginal tumor dose was 30 Gy (range, 20-36 Gy) in a median 5 fractions (range, 3-5 fractions). The median follow-up time was 42 months (range, 17-63 months). At the time of analysis, 10 (91%) patients were alive and 1 (9%) had died due to tumor progression. Of 10 patients, 8 (73%) had stable disease and the remaining 2 (18%) had progressive disease. The actuarial overall survival (OS) after FSRS was 91% at two-years. Two patients developed radiation-induced brain necrosis as a complication in the 8th and 28th months of follow-up, respectively. Our results with robotic FSRS in skull base chordomas are promising for selected patients. However, due to the slow growth pattern of skull base chordomas, a longer follow-up is required to determine exact treatment results and late morbidity.


Assuntos
Cordoma/radioterapia , Radiocirurgia/métodos , Neoplasias da Base do Crânio/radioterapia , Adolescente , Adulto , Cordoma/patologia , Fracionamento da Dose de Radiação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Base do Crânio/patologia
9.
Ann Oncol ; 24 Suppl 7: vii5-10, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24001764

RESUMO

Cancer is now the fastest growing killing disease in the Middle East. Accordingly, there is an urgent need to train local health professionals: oncologists, palliative care experts, oncology nurses, psychologists, along with social workers, physiotherapists and spiritual counselors on strategies for early detection, curative therapies and palliation. Professionals in the region, along with the public, need to convince medical administrators, regulators and policymakers about investing in education and training of YOUNG professionals, as well as those with already proven experience in cancer care. Training is the basis for any future cancer care program, which aims at the integration of palliative care practices into standard oncology care across the trajectory of the illness.


Assuntos
Educação Médica , Necessidades e Demandas de Serviços de Saúde , Neoplasias/terapia , Cultura , Educação Médica/economia , Educação Médica/estatística & dados numéricos , Educação Médica/tendências , Pessoal de Saúde , Humanos , Oriente Médio , Relações Médico-Paciente , Atenção Primária à Saúde , Resultado do Tratamento
10.
Ann Oncol ; 24(4): 944-52, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23172637

RESUMO

BACKGROUND: Primary data on training experiences of European gynaecological oncology trainees are lacking. This study aims to evaluate trainee profile, satisfaction and factors affecting the training experience in gynaecological oncology in Europe. PATIENTS AND METHODS: A web-based anonymous survey sent to ENYGO members/trainees in July 2011. It included sociodemographic information and a 22-item (1-5 Likert scale) questionnaire evaluating training experience in gynaecological oncology. Chi-square tests were used for evaluating the independence of categorical variables and t-test (parametric)/Mann-Whitney (non-parametric) tests for differences between two independent groups on continuous data. Cluster analysis was used to identify groupings in multivariate data and Cronbach's-alpha for questionnaire reliability. A multivariable linear regression model was used to assess the effect of variables on training satisfaction. RESULTS: One hundred and nineteen gynaecological-oncology trainees from 31 countries responded. The mean age was 37.4 (S.D, 5.3) years and 55.5% were in accredited training posts. Two clusters identified in the cohort (Calinski-Harabasz, CH = 47.35) differed mainly by accredited training (P = 0.003). The training-satisfaction score (TSS) had high reliability (Cronbach's alpha, 0.951) and was significantly associated with accredited posts (P < 0.0005), years of training (P = 0.001) and salary (P = 0.002). The TSS was independent of age (P = 0.360), working hours (P = 0.620), overtime-pay (P = 0.318), annual leave (P = 0.933), gender (P = 0.545) and marital status (P = 0.731). Accredited programme trainees scored significantly higher than others in 17 of 22 aspects of training. The areas of greater need included advanced laparoscopic/urological/colorectal surgery, radiation oncology, palliative-care, cancer genetics and research opportunities. CONCLUSIONS: Our data demonstrate the importance of accredited training and the need for harmonisation of gynaecological oncology training within Europe.


Assuntos
Educação Médica Continuada , Oncologia , Adulto , Europa (Continente) , Feminino , Humanos , Masculino , Oncologia/educação , Neoplasias/terapia , Cuidados Paliativos , Inquéritos e Questionários , Recursos Humanos
11.
Ann Oncol ; 23 Suppl 3: 15-28, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22628412

RESUMO

BACKGROUND: In larger parts of the Middle East palliative care is still misunderstood among health professionals, cancer patients and the public at large. One reason to that is because the term does not obviously communicate the intent of this clinical discipline, which is lending better quality of life while combating cancer. Further, culture, tradition and religion have contributed to this misgiving and confusion especially at the terminal stage of the disease. METHODS: The Middle East Cancer Consortium jointly with the American Society of Clinical Oncology, the American Oncology Nursing Society, the San Diego Hospice Center for Palliative Medicine and the Children's Hospital & Clinics of Minnesota initiated a series of training courses and workshops in the Middle East to provide updated training to physicians, nurses, social workers and psychologists from throughout the region with basic concepts of palliative care and pain managements in adults and children cancers. RESULTS: During the past 6 years hundreds of professionals took part in these educational and training activities, thereby creating the core of trained caregivers who start to make the change in their individual countries. CONCLUSIONS: The outcome of consecutive training activities can overcome geopolitical instabilities, and yield a genuine change in approach of both regulators, medical administrators, medical staff and the public; as to the important contribution of palliative care services to the welfare of the patient and his/her family.


Assuntos
Neoplasias/terapia , Cuidados Paliativos/métodos , Analgésicos Opioides/uso terapêutico , Feminino , Acessibilidade aos Serviços de Saúde , Humanos , Masculino , Oriente Médio , Neoplasias/complicações , Dor/tratamento farmacológico , Dor/etiologia , Cuidados Paliativos/tendências
12.
Ann Oncol ; 23 Suppl 3: 76-8, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22628421

RESUMO

An organized palliative care system was lacking in Turkey before 2010. One of the pillars of Turkish Cancer Control Programme is palliative care. The Pallia-Turk project in this respect has been implemented by the Ministry since 2010. The project is unique since it is population based and organized at the primary level. This means, the whole population (>70 million) will have the quickest and easiest way for access to palliative care. This manuscript briefly summarizes the situation before the project and updates what has been done in last 2 years with the project.


Assuntos
Serviços de Saúde Comunitária/métodos , Neoplasias/terapia , Cuidados Paliativos/métodos , Atenção à Saúde/métodos , Humanos , Turquia
13.
Minerva Ginecol ; 62(5): 433-45, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20938428

RESUMO

Endometrial hyperplasia is a commonly seen clinical entity. A great majority of patients present with abnormal uterine bleeding. Unopposed estrogen either from an endogenous or exogenous source is the most important etiologic factor. Etiologic evaluation and cause specific treatment is a must for these patients instead of direct biopsies and treatments. Clinical importance of this pathological entity is the underlying risk of carrying a concomitant genital cancer and the potential risk of progression to endometrial carcinoma during the follow-up. Despite to a great effort on research and a long history of the disease in the medical literature; we still do not have a practical and accurate system available to use during daily practice in order to differentiate the real precancerous lesions. Treatment of endometrial hyperplasia depends on the patient's age, fertility desire and the type of present hyperplasia. Progestagens are still the most commonly used medical treatment modality in these patients. Response rates are higher in cases without atypia. In selected cases, hysterectomy may be performed as a definitive treatment modality. In this review article current management of the endometrial hyperplasia is summarized in the light of associated literature.


Assuntos
Hiperplasia Endometrial/diagnóstico , Hiperplasia Endometrial/terapia , Árvores de Decisões , Hiperplasia Endometrial/classificação , Feminino , Humanos
14.
Gynecol Oncol ; 119(1): 131-5, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20638108

RESUMO

OBJECTIVE: The aim of this study was to evaluate the prevalence and spectrum of a known founder mutation, 5382insC and large genomic rearrangements (LGRs) in BRCA1 in ovarian cancer patients in Turkey. The additional aim was to determine the genetic testing strategy in Turkish breast/ovarian cancer family. METHODS: Six hundred and sixty-seven ovarian cancer patients from five large geographical regions in Turkey, 61 of which had family history of breast/ovarian cancer, were tested for the mutation 5382insC by mutagenically separated polymerase chain reaction and direct sequencing of the entire coding sequence and the splicing sites. Additionally, multiplex ligation-dependent probe amplification (MLPA) was performed for large mutational scanning of BRCA1 gene in unselected ovarian cancer. RESULTS: In this study, BRCA1 point mutations were observed in 1% of all patients and 9.8% of familial cases: 5382insC, unique novel missense variant-G1748S and unclassified splice site variant IVS20+5A>T. 5382insC was observed in two patients. However, G1748S, previously unreported, was found in four patients and thus led to the conclusion that this mutation may be unique to Turkey. A splice site variant, IVS20+5A>T, was detected in three patients, with two of them including G1748S and IVS20+5A>T, together. Using MLPA, six different distinct LGRs in BRCA1 were observed: the deletion of E1A-1B-2, E11, E17-19, E18 and E18-19 and duplication of E5-9. The prevalence of LGRs in this study was 40.9% among patients with family history. The deletion of E1A-1B-2 was the common mutation, and patients with this deletion were referred to us from four different geographical regions in Turkey. Therefore, it was hypothesized that this deletion covering E1-2 is common in Turkey. CONCLUSION: LGRs in BRCA1 were strongly associated with positive family history among the Turkish population. On the basis of these findings, it can be recommended that a low-cost screening for LGRs in BRCA1 may be the first-line mutation detection method in families with strong breast/ovarian cancer history in Turkey.


Assuntos
Rearranjo Gênico , Genes BRCA1 , Neoplasias Ovarianas/genética , Mutação Puntual , Estudos de Casos e Controles , DNA de Neoplasias/sangue , DNA de Neoplasias/genética , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Ovarianas/sangue , Turquia
15.
Eur J Gynaecol Oncol ; 30(4): 396-401, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19761130

RESUMO

Endometrial hyperplasia is a commonly seen disorder in daily gynecology practice. The clinical importance of this pathological entity is the underlying risk of carrying a concomittant genital cancer or risk of progression to endometrial carcinoma during the follow-up. Despite recent advances in non-invasive techniques to define underlying endometrial cancer during the initial diagnosis of endometrial hyperplasia, none of these studies are conclusive yet. Today, in spite of intense discussions and related studies which aimed to define certain prognostic factors (WHO94 vs EIN) to predict cases that would progress to cancer, we still do not have a practical and accurate system available to use during daily practice. Treatment of endometrial hyperplasias depends on the patient's age, fertility desire and the type of hyperplasia. Progestagens are still the most commonly used medical treatment modality in these patients. Response rates are higher for cases without atypia. In selected cases, hysterectomy may be performed as a definitive treatment modality. In this review article, the current management of endometrial hyperplasias is summarized in light of the associated literature. We also give a brief overview of the EIN classification and its clinical importance.


Assuntos
Hiperplasia Endometrial/terapia , Neoplasias do Endométrio/terapia , Hiperplasia Endometrial/diagnóstico , Hiperplasia Endometrial/patologia , Neoplasias do Endométrio/diagnóstico , Neoplasias do Endométrio/patologia , Feminino , Humanos , Prognóstico , Fatores de Risco
16.
Eur J Gynaecol Oncol ; 30(1): 9-12, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19317248

RESUMO

Primary breast carcinoma is the most common malignancy in women, however, metastatic breast carcinoma is rarely seen in clinical practice. It has been reported that lymphoma-leukemia, melanoma and sarcomas, the most common primary malignancies, can metastasize to the breast. On the other hand, ovarian carcinoma and other gynecologic cancers rarely develop into breast metastasis. However, the incidence of breast metastasis arising from ovarian carcinoma might be increasing as a result of prolongation in survival and improvement in treatment modalities. Bilateral breast metastasis originating from an ovarian carcinoma is an extremely rare clinico-pathological situation. In our literature review we found just nine cases of bilateral breast metastasis from primary ovarian carcinoma. In this study, the mean age was 46 years (range 16-68). Mean interval from initial diagnosis of ovarian carcinoma to bilateral breast metastases was 22 months (range 11-24) and mean survival was 12 (range 5-27) months after the diagnosis of breast metastasis. Serous papillary adenocarcinoma was the predominant histological subtype. Interestingly, five of the nine (56%) cases reported were from Turkey. This interesting observation can be explained by a genetic predisposition, but it requires further research. In conclusion, although it is a rare entity, breast metastasis should not be ruled out in patients with a history of ovarian carcinoma, if patients present with any symptoms of breast diseases.


Assuntos
Adenocarcinoma Papilar/secundário , Neoplasias da Mama/secundário , Cistadenocarcinoma Seroso/secundário , Neoplasias Ovarianas/patologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Adulto Jovem
17.
Eur J Gynaecol Oncol ; 29(3): 242-5, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18592787

RESUMO

Primary cytoreductive surgery followed by combination chemotherapy of paclitaxel and cisplatinum is the standard treatment for advanced staged epithelial ovarian cancers. Despite the maximal efforts to increase optimal cytoreductive success rates and related ultra-radical surgeries, five-year survival rates are still poor. Primary cytoreductive surgeries and their radicalities have been criticized since the early nineties. Interval debulking surgery (IDS) and neo-adjuvant chemotherapy (NAC) are the two suggested alternatives to the primary debulking approaches. In this article, the authors summarize and discuss the IDS approach with an associated literature review.


Assuntos
Carcinoma/cirurgia , Procedimentos Cirúrgicos em Ginecologia/tendências , Neoplasias Ovarianas/cirurgia , Antineoplásicos/uso terapêutico , Carcinoma/tratamento farmacológico , Carcinoma/patologia , Terapia Combinada , Feminino , Previsões , Procedimentos Cirúrgicos em Ginecologia/métodos , Humanos , Terapia Neoadjuvante , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Taxa de Sobrevida
18.
Int J Biol Markers ; 22(3): 194-9, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17922462

RESUMO

Recent studies suggest that plasma Epstein-Barr virus (EBV) DNA may reflect tumor burden in patients with nasopharyngeal cancer. A prospective study was initiated to investigate this correlation in 125 patients (34 pretreatment [Group A], 78 in remission [Group B] and 13 relapsed [Group C]) and 19 healthy controls. In group A, EBV DNA was detected in plasma samples of 24 (70%) patients. In Group B, EBV DNA was detected in 7 patients (range 77-13,731 copies/mL) and further imaging in all but one of these patients revealed active disease confirmed by ultrasound-guided fine-needle biopsy. There was only one false-positive case; this patient is currently under follow-up. Here we describe 2 of the 7 patients with detectable plasma EBV DNA in whom recurrence was documented by PET scan during follow-up. Our results showed that in group B the positive predictive value of quantitative analysis of plasma EBV DNA was 85%. Quantitative analysis of EBV DNA in plasma seems to become an integral part of screening, staging, monitoring, and prediction of relapse in patients with nasopharyngeal carcinoma. However, previous studies cannot be considered definitive and more reports on the use of this technique are urgently needed from both endemic and non-endemic regions.


Assuntos
Biomarcadores Tumorais/sangue , DNA Viral/sangue , Infecções por Vírus Epstein-Barr/virologia , Herpesvirus Humano 4/genética , Neoplasias Nasofaríngeas/virologia , Biomarcadores Tumorais/genética , DNA Viral/genética , Infecções por Vírus Epstein-Barr/sangue , Infecções por Vírus Epstein-Barr/complicações , Fluordesoxiglucose F18 , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/sangue , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/patologia , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/virologia , Estadiamento de Neoplasias , Reação em Cadeia da Polimerase/métodos , Tomografia por Emissão de Pósitrons , Estudos Prospectivos , Compostos Radiofarmacêuticos
19.
Int J Gynecol Cancer ; 17(1): 68-75, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17291234

RESUMO

Ascites is a common finding in patients with epithelial ovarian cancer (EOC). Clinico-pathologic correlations with respect to the presence of ascites, positive cytology and prognostic role of ascites, and the impact of ascitic volumes were not previously studied extensively. A total of 372 patients with EOC were retrospectively evaluated with respect to presence and amount of ascites, cytologic findings, and survival. Two groups were compared by using Chi-square, Student's t and Mann-Whitney U, binary logistic regression, Kaplan Meier and Cox-regression analysis tests, where appropriate. Omental metastasis (P < 0.001; OR: 3.21, 95% CI = 1.945-5.297) and mean number of metastatic lymph nodes (P= 0.008; OR: 1.063, 95% CI = 1.016-1.112) were significantly related with presence of ascites. Evaluation of ascitic volume at different thresholds revealed lymphatic-omental metastasis, and also the disease stage to be significantly different among patient groups at lower threshold values and the positive cytology and high-grade diseases at higher threshold values. In conclusion, presence of ascites correlates with both the intraperitoneal and also the retroperitoneal tumor spread. Amount of ascites has different correlations with the clinico-pathologic factors depending on the thresholds chosen. At lower volumes, lymphatic and omental metastasis seems to correlate with the development of ascites. Once ascites develops, tumor grade seems to be important for larger ascites volumes. Neither the presence of ascites or its volume nor the cytologic positivity was an independent predictor of survival.


Assuntos
Neoplasias Ovarianas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ascite/patologia , Células Epiteliais/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Taxa de Sobrevida
20.
Int J Gynaecol Obstet ; 96(2): 117-21, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17239881

RESUMO

OBJECTIVE: To compare the effects of topical testosterone and clobetasol treatments on symptoms remission and recurrence rates in patients with vulvar lichen sclerosus (LS). METHODS: A retrospective review of the records showed that, of 140 patients with biopsy-proven vulvar LS, 80 were treated with applications of testosterone propionate 2% in petrolatum and 60 with clobetasol 17-propionate 0.05%. RESULTS: The response rates after 6 months were 77.5% for patients treated with testosterone and 91.7% for those treated with clobetasol (P=0.02). The recurrence rates were 20% and 6.7% in the 2 groups, respectively (P=0.02). Premenopausal patients had higher remission rates and lower recurrence rates than postmenopausal patients (P>0.05). Considering whole patients, low remission rates and high recurrence rates were observed in patients who had had a hysterectomy (P>0.05). CONCLUSION: Treatment of LS with a corticosteroid provided excellent remission rates. In this study, clobetasol 17-propionate 0.05% was superior to testosterone for both remission induction and maintenance therapy.


Assuntos
Androgênios/uso terapêutico , Clobetasol/uso terapêutico , Glucocorticoides/uso terapêutico , Propionato de Testosterona/uso terapêutico , Líquen Escleroso Vulvar/tratamento farmacológico , Administração Tópica , Adulto , Androgênios/administração & dosagem , Feminino , Humanos , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Propionato de Testosterona/administração & dosagem
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