Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 32
Filtrar
1.
J Appl Clin Med Phys ; 22(6): 172-182, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33939267

RESUMO

Dose escalation is key for improved outcomes in intermediate-risk prostate cancer, including unfavorable intermediate-risk (UIR) cases. This educational report is designed to provide information about our quality high-dose 125 I seed implantation monotherapy technique in which a biologically effective dose (BED) â‰§ 200 Gy is applied for treatment of intermediate-risk prostate cancer. This protocol is named the "Ten-step Method," where the rationale and principle of the method are based on the following four goals: (1) The entire prostate should be covered by the prescription isodose distribution with a sufficient margin from the prostatic capsule, achieving high D90 and V100 values by 125 I seed implantation. (2) The high-dose cloud (240 Gy) should not invade the urethra or rectum. (3) In order to achieve goals (1) and (2), make the high-dose cloud intentionally along the periphery (bilateral wall to anterior wall) away from the urethra and rectum. (4) In order to achieve goal (3), seeds at the periphery, except those anterior to the rectal wall, should be placed just 1mm inside the capsule. The data obtained from a total of 137 patients with intermediate-risk prostate cancer treated with low-dose-rate (LDR) monotherapy are shown. The dosimetry parameters were monitored at 1 month after seed implantation by using CT and MRI fusion guidance. The data at 1 month after LDR were: Average D90, BED, and V100 of 125 I LDR monotherapy were 194.1 Gy, 207.3 Gy, and 99%, respectively. This ten-step method was reproducible in 137 patients with intermediate-risk prostate cancer, allowing administration of high-dose monotherapy with excellent clinical outcomes.


Assuntos
Braquiterapia , Neoplasias da Próstata , Humanos , Masculino , Neoplasias da Próstata/radioterapia , Dosagem Radioterapêutica , Reto
2.
Lancet ; 387(10029): 1762-74, 2016 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-26651223

RESUMO

Testicular germ cell tumours are at the crossroads of developmental and neoplastic processes. Their cause has not been fully elucidated but differences in incidences suggest that a combination of genetic and environment factors are involved, with environmental factors predominating early in life. Substantial progress has been made in understanding genetic susceptibility in the past 5 years on the basis of the results of large genome-wide association studies. Testicular germ cell tumours are highly sensitive to radiotherapy and chemotherapy and hence have among the best outcomes of all tumours. Because the tumours occur mainly in young men, preservation of reproductive function, quality of life after treatment, and late effects are crucial concerns. In this Seminar, we provide an overview of advances in the understanding of the epidemiology, genetics, and biology of testicular germ cell tumours. We also summarise the consensus on how to treat testicular germ cell tumours and focus on a few controversies and improvements in the understanding of late effects of treatment and quality of life for survivors.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/terapia , Orquiectomia , Proteínas Proto-Oncogênicas c-kit/genética , Neoplasias Testiculares/terapia , Proteínas ras/genética , Quimioterapia Adjuvante , Estudo de Associação Genômica Ampla , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias Embrionárias de Células Germinativas/genética , Radioterapia Adjuvante , Neoplasias Testiculares/epidemiologia , Neoplasias Testiculares/genética
3.
Nihon Hinyokika Gakkai Zasshi ; 106(4): 289-92, 2015 Oct.
Artigo em Japonês | MEDLINE | ID: mdl-26717790

RESUMO

A 6-month-old boy was referred to our hospital with left scrotal swelling. Scrotal ultrasound examination revealed a 2 cm cystic mass without solid component in left testicular parenchyma. Serum AFP, hCG and LDH levels were within normal limits. Although we suspected a simple cyst of the testis or a benign testicular tumor, the left testicle was explored via an inguinal incision in case of malignancy. Since intraoperative frozen section revealed benign, we preserved the remaining testis. The wall of cystic mass had a small solid lesion. The definitive pathological examination of the cyst wall showed mature teratoma including squamous epithelium, glandular epithelium of enteric type and cartilage. At 4 years of follow up, he was free of recurrence without testicular atrophy.


Assuntos
Teratoma , Neoplasias Testiculares/patologia , Cistos/cirurgia , Humanos , Lactente , Masculino , Teratoma/cirurgia , Neoplasias Testiculares/cirurgia , Resultado do Tratamento
4.
J Magn Reson Imaging ; 38(4): 897-904, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23417820

RESUMO

PURPOSE: To evaluate the accuracy and feasibility of magnetic resonance voiding cystourethrography (MRVCUG), with or without contrast medium, in detecting vesicoureteral reflux (VUR) by comparison with conventional voiding cystourethrography (VCUG). MATERIALS AND METHODS: Seventy-five patients underwent a series of 55 indirect MRVCUG (I-MRVCUG) and 61 direct MRVCUG (D-MRVCUG) between 2003 and 2009. We retrospectively compared the results from I-MRVCUG and D-MRVCUG with those from VCUG on 150 kidney-ureter units. Ratios of successful completion of the two types of MRVCUG were analyzed in 116 examinations according to sex, age, and among the two groups, with or without sedation. RESULTS: D-MRVCUG was superior to I-MRVCUG in detecting VUR (sensitivity: 96.8% vs. 76.9%; specificity: 96.3% vs. 88.7%; agreement: 96.6% vs. 83.7%; kappa: 0.83 [95% confidence interval (CI): 0.72, 0.94] vs. 0.55 [95% CI: 0.41, 0.69]). The overall ratio of successful completion of the two types of MRVCUG was 76.7% (89/116): there was no significant difference between I-MRVCUG and D-MRVCUG. The successful completion rate was significantly lower in MRVCUG in toddlers compared with preschoolers, infants, schoolchildren, and adults (P < 0.001). CONCLUSION: The two types of MRVCUG (I-MRVCUG and D-MRVCUG) are promising tests without radiation exposure. Both I-MRVCUG and D-MRVCUG are feasible for children except for toddlers.


Assuntos
Imageamento por Ressonância Magnética , Bexiga Urinária/patologia , Refluxo Vesicoureteral/diagnóstico , Adolescente , Adulto , Fatores Etários , Criança , Pré-Escolar , Meios de Contraste/química , Feminino , Humanos , Lactente , Rim/patologia , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Resultado do Tratamento , Ureter/patologia , Refluxo Vesicoureteral/fisiopatologia , Adulto Jovem
5.
Int J Urol ; 20(5): 544-6, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23072289

RESUMO

We report a rare case of stage I non-seminomatous testicular germ cell tumor with malignant transformation. The patient received two cycles of chemotherapy (cisplatin, bleomycin and etoposide) tailored to testicular germ cell tumors as an adjuvant therapy after orchiectomy. However, 22 months later, the patient developed a metastasis in the occipital region that consisted of solely rhabdomyosarcoma through malignant transformation of a teratoma component. This case highlights an issue related to adjuvant chemotherapy for testicular germ cell tumors with components of malignant transformation.


Assuntos
Neoplasias Encefálicas/secundário , Neoplasias Embrionárias de Células Germinativas/patologia , Osso Occipital/patologia , Rabdomiossarcoma/secundário , Neoplasias Cranianas/secundário , Neoplasias Testiculares/patologia , Adulto , Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Quimioterapia Adjuvante , Evolução Fatal , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Rabdomiossarcoma/tratamento farmacológico , Neoplasias Cranianas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico
6.
Mol Carcinog ; 51(9): 711-22, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21809391

RESUMO

Testicular germ cell tumors (TGCTs) have a unique epigenetic profile distinct from that of other types of cancer. To further evaluate epigenetics of TGCTs, this study examines DNA methylation patterns of DNA repetitive elements in TGCTs. Bisulfite genomic sequencing and combined bisulfite restriction analysis (COBRA) were used to analyze the methylation patterns of DNA repetitive elements (LINE1 and Alu repeats) in embryonal carcinoma (EC) derived cell lines, primary TGCT tissues, noncancerous testicular tissues adjacent to TGCTs and cancer cells derived from somatic tissues (testicular malignant lymphoma tissues and renal cell carcinoma cell lines). Through both bisulfite genomic sequencing and COBRA, LINE1 was extensively hypomethylated in both seminomatous and nonseminomatous TGCT tissues as well as EC cell lines. We studied two Alu repeats locating in the 5' end of E-cadherin and XIST by bisulfite genomic sequencing. These two Alu elements were extensively hypomethylated in seminomatous TGCTs, but methylated in nonseminomatous TGCTs, including two EC derived cell lines. This increased unmethylated profile in seminomatous TGCTs was observed also by COBRA for Alu repeats. Although partial demethylation of DNA repetitive elements was observed in cancer cells of somatic tissue origin, the degree of demethylation was more pronounced in TGCTs than in cancer cells of somatic tissue origin. We observed abnormal demethylation of DNA repetitive elements in some of the tissues adjacent to TGCTs. The results indicate that the underlying mechanisms to undergo or maintain demethylation of DNA repetitive sequences differ between TGCTs and cancer cells of somatic tissue origin.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA , Perfilação da Expressão Gênica , Linfoma/genética , Neoplasias Embrionárias de Células Germinativas/genética , Sequências Repetitivas de Ácido Nucleico/genética , Neoplasias Testiculares/genética , Adulto , Idoso , Western Blotting , Carcinoma Embrionário/genética , Carcinoma de Células Renais/genética , DNA (Citosina-5-)-Metiltransferases/antagonistas & inibidores , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA de Neoplasias/genética , Epigênese Genética , Humanos , Neoplasias Renais/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , RNA Interferente Pequeno/genética , Testículo/metabolismo , Células Tumorais Cultivadas , Adulto Jovem
7.
J Urol ; 187(5): 1876-81, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22425046

RESUMO

PURPOSE: Some nonseminomatous germ cell tumors are resistant to any type of chemotherapy. Control of embryonal carcinoma cells is crucial to manage nonseminomatous germ cell tumors. We established SOX2 targeting therapy in an embryonal carcinoma model. MATERIALS AND METHODS: SOX2 expression was evaluated in a series of testicular germ cell tumor tissue samples. The antitumor effect of SOX2 knockdown was analyzed in vitro and in vivo using an embryonal carcinoma model. RESULTS: In testicular germ cell tumor tissue SOX2 was expressed in the foci of embryonal carcinoma but negative in seminoma and yolk sac tumors. In an embryonal carcinoma model SOX2-siRNA induced apoptotic cell death in vitro and significant growth suppression in vivo. CONCLUSIONS: This study shows the therapeutic potential of SOX2 silencing for embryonal carcinoma. However, further improvements are needed in SOX2-siRNA delivery to the tumor.


Assuntos
Carcinoma Embrionário/metabolismo , Carcinoma Embrionário/terapia , Fatores de Transcrição SOXB1/antagonistas & inibidores , Fatores de Transcrição SOXB1/metabolismo , Neoplasias Testiculares/metabolismo , Neoplasias Testiculares/terapia , Animais , Carcinoma Embrionário/patologia , Morte Celular , Linhagem Celular Tumoral , Modelos Animais de Doenças , Inativação Gênica , Imuno-Histoquímica , Masculino , Camundongos , Camundongos Endogâmicos , RNA Interferente Pequeno/uso terapêutico , Seminoma/metabolismo , Seminoma/patologia , Neoplasias Testiculares/patologia , Transfecção
8.
Int J Urol ; 19(6): 504-11, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22375557

RESUMO

Testicular germ cell tumors are neoplasms carrying two unique features. First, testicular germ cell tumors have a pluripotential nature and show protean histology ranging from that of germ cells to embryonal and differentiated somatic cells. Therefore, testicular germ cell tumors are interesting resources positioned at a crossroad in developmental and neoplastic processes. The second unique feature of testicular germ cell tumors is their exquisite sensitivity to cisplatin-based chemotherapy. This review summarizes recent research progress in the epigenetics of testicular germ cell tumors in an attempt to explain the abovementioned biological and clinical characteristics of testicular germ cell tumors.


Assuntos
Epigenômica , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Testiculares/genética , Elementos Alu , Antineoplásicos/uso terapêutico , Biomarcadores/metabolismo , Cromossomos Humanos X/genética , Cisplatino/uso terapêutico , Ilhas de CpG/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Metilação de DNA , Resistencia a Medicamentos Antineoplásicos/genética , Células-Tronco Embrionárias/metabolismo , Genes Supressores de Tumor , Impressão Genômica , Humanos , Sequências Repetitivas Dispersas , Elementos Nucleotídeos Longos e Dispersos , Masculino , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Regiões Promotoras Genéticas , RNA Longo não Codificante , RNA não Traduzido/genética , Neoplasias Testiculares/tratamento farmacológico , Inativação do Cromossomo X
9.
J Contemp Brachytherapy ; 14(5): 476-480, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36478704

RESUMO

Purpose: Prostate ductal adenocarcinoma (PDA) is an aggressive, rare variant of histologic sub-type of prostate cancer. Patients with PDA present with more aggressive clinical features and have a poorer prognosis than patients with acinar adenocarcinoma. So far, an optimal treatment for PDA has yet to be established. Furthermore, the effectiveness of low-dose-rate (LDR) brachytherapy for PDA has not been reported previously. Case presentation: In this paper, we present two case reports on very high-risk locally advanced PDA, in which patients were successfully treated with LDR brachytherapy, with seminal vesicle implantation in combination with external beam radiotherapy (EBRT) at a biologically effective dose (BED) ≥ 220 Gy and short-term androgen deprivation therapy (ADT). There was no grade 2 genitourinary (GU) and gastrointestinal (GI) toxicities during follow-up, and no evidence of hematuria nor rectal bleeding during follow-up. The patients stay healthy without biochemical failure and without bowel or urinary difficulties at 11.5 years and 8 years, respectively. Conclusions: High-BED LDR-based radiotherapy in combination with EBRT (BED ≥ 220 Gy) may be an ideal treatment for very high-risk locally advanced PDA patients.

11.
J Contemp Brachytherapy ; 13(1): 91-94, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34025741

RESUMO

PURPOSE: Prostate cancer with nodular bladder invasion (stage T4 prostate cancer) is an extremely difficult clinical entity to achieve complete cure. So far, there has been no clear report demonstrating complete cure of prostate cancer with nodular bladder invasion, stage T4 prostate cancer. CASE PRESENTATION: In this case report, the author presents a 55-year-old man with a diagnosis of advanced prostate cancer invading into the bladder wall with pelvic lymph node metastasis (T4N1M0 disease). The patient was treated with biologically effective dose (BED) ≥ 220 Gy of high-dose radiotherapy, using low-dose-rate (LDR) brachytherapy in combination with whole pelvis (WP) external beam radiotherapy (EBRT) and short-term androgen deprivation therapy (ADT): neo-adjuvant six months plus adjuvant six months ADT. There was no grade 2 genitourinary (GU) and gastrointestinal (GI) toxicity during follow-up. There was no evidence of hematuria, nor rectal bleeding in the follow-up. The patient stays healthy without biochemical failure and without bowel and urinary troubles at six years. CONCLUSIONS: Along with previous outstanding data of BED ≥ 220 Gy LDR-based radiotherapy for high-risk and very high-risk prostate cancer patents, including pelvic lymph node metastasis, the present report, in which the patient was treated with BED ≥ 220 Gy of high-dose radiotherapy, LDR brachytherapy in combination with WP EBRT may be an optimal treatment for prostate cancer with nodular bladder invasion with lymph node metastasis (T4N1disease).

12.
Int J Urol ; 17(1): 96-8, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20377831

RESUMO

Crossed renal ectopia with fusion is a rare anomaly of the kidney. The present case report describes a 67-year-old man with renal tumor who had been diagnosed as having a crossed ectopic kidney with fusion for 25 years. The pathological diagnosis of the primary tumor specimen was Wilms' tumor with favorable histology. Upon tumor recurrence, molecular detection of SYT-SSX2 fusion transcripts lead to the diagnosis of synovial sarcoma of the kidney. To our knowledge, this is the first case of primary synovial sarcoma arising from a crossed ectopic kidney with fusion.


Assuntos
Neoplasias Renais/complicações , Rim/anormalidades , Sarcoma Sinovial/complicações , Idoso , Humanos , Masculino
13.
Int J Urol ; 17(8): 734-6, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20604815

RESUMO

We report a rare case of multiple schwannomas presenting with scrotal mass. In the present case, a scrotal schwannoma developed in a 66-year-old man with a history of brain tumor surgery. Investigating the patient's past history lead to the diagnosis as probable schwannomatosis. Patients with schwannomatosis are at increased risk of developing multiple schwannomas and these patients need regular surveillance. In this regard, the present case highlights the importance of thorough history taking in patients with scrotal schwannoma.


Assuntos
Neoplasias Cerebelares/patologia , Neoplasias dos Genitais Masculinos/patologia , Segunda Neoplasia Primária/patologia , Síndromes Neoplásicas Hereditárias/patologia , Neurilemoma/patologia , Escroto , Idoso , Neoplasias dos Genitais Masculinos/diagnóstico , Humanos , Masculino , Neurilemoma/diagnóstico
14.
J Contemp Brachytherapy ; 12(1): 6-11, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32190064

RESUMO

PURPOSE: To monitor the outcomes for intermediate-risk prostate cancer patients treated with biologically effective dose (BED) ≥ 200 Gy radiotherapy using low-dose-rate (LDR) brachytherapy. MATERIAL AND METHODS: Between 2005 and 2016, a total of 397 patients with intermediate-risk prostate cancer were treated by LDR-based radiotherapy with a BED ≥ 200 Gy. Treatments consisted of LDR brachytherapy alone (177 cases) or LDR and external beam radiotherapy (EBRT) (220 cases). Short-term androgen deprivation therapy (ADT) was used in 186 patients (46.9%). The median follow-up period was 72 months (range 29-165 months). Dosimetric parameters and BED were studied in each case. The numbers of intermediate-risk features were: 163 patients with 1 intermediate-risk feature (41%), 169 patients with 2 intermediate-risk features (43%), and 65 patients with 3 intermediate-risk features (16%). A total of 145 cases were diagnosed as having primary Gleason pattern 4: Gleason score 4 + 3 (36.5%). RESULTS: Three patients developed biochemical failure, thus providing a 7-year actual biochemical failure-free survival (BFFS) rate of 99.1%. Biochemical failure was observed exclusively in cases with distant metastasis: two cases with lymph node metastasis and one case with bone metastasis, thus yielding a 7-year freedom from clinical failure (FFCF) rate of 99.1%. We observed eight deaths, but there was no death from prostate cancer, thus yielding a 7-year cause-specific survival (CSS) rate of 100%, and an overall survival (OS) rate of 98.4%. CONCLUSIONS: This study highlights excellent outcomes for intermediate-risk prostate cancer patients, including unfavorable intermediate-risk cases, treated with BED ≥ 200 Gy radiotherapy using LDR brachytherapy. LDR alone with a BED of 200 Gy may be an optimal treatment for both favorable and unfavorable intermediate-risk prostate cancer patients, although a longer follow-up is mandatory to confirm the present findings.

16.
J Contemp Brachytherapy ; 9(1): 1-6, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28344597

RESUMO

PURPOSE: To evaluate the outcomes of high-risk prostate cancer patients treated with biologically effective dose (BED) ≥ 220 Gy of high-dose radiotherapy, using low-dose-rate (LDR) brachytherapy in combination with external beam radiotherapy (EBRT) and short-term androgen deprivation therapy (ADT). MATERIAL AND METHODS: From 2005 to 2013, a total of 143 patients with high-risk prostate cancer were treated by radiotherapy of BED ≥ 220 Gy with a combination of LDR brachytherapy, EBRT, and androgen deprivation therapy (ADT). The high-risk patients in the present study included both high-risk and very high-risk prostate cancer. The number of high-risk features were: 60 patients with 1 high-risk factor (42%), 61 patients with 2 high-risk factors (43%), and 22 patients with 3 high-risk factors (15%) including five N1 disease. External beam radiotherapy fields included prostate and seminal vesicles only or whole pelvis depending on the extension of the disease. Biochemical failure was defined by the Phoenix definition. RESULTS: Six patients developed biochemical failure, thus providing a 5-year actual biochemical failure-free survival (BFFS) rate of 95.2%. Biochemical failure was observed exclusively in cases with distant metastasis in the present study. All six patients with biochemical relapse had clinical failure due to bone metastasis, thus yielding a 5-year freedom from clinical failure (FFCF) rate of 93.0%. None of the cases with N1 disease experienced biochemical failure. We observed four deaths, including one death from prostate cancer, therefore yielding a cause-specific survival (CSS) rate of 97.2%, and an overall survival (OS) rate of 95.5%. CONCLUSIONS: High-dose (BED ≥ 220 Gy) radiotherapy by LDR in combination with EBRT has shown an excellent outcome on BFFS in high-risk and very high-risk cancer, although causal relationship between BED and BFFS remain to be explained further.

17.
Oncogene ; 23(36): 6163-9, 2004 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-15195139

RESUMO

The increased risk of several types of cancer in Klinefelter syndrome (47XXY) suggests that the extra X chromosome may be involved in the tumorigenesis associated with this syndrome. Here, we show that cancer cells (PSK-1) derived from a patient with Klinefelter syndrome (47XXY) showing loss of an inactive X chromosome subsequently gained active X chromosomes. We found that this abnormal X chromosome composition in PSK-1 is caused by a loss of an inactive X chromosome followed by multiplication of identical active X chromosomes, not by reactivation of an inactive X chromosome. Furthermore, we extended the characterization of loss-of-inactive X in a series of 22 female-derived cancer cell lines (eight breast cancer cell lines, seven ovarian cancer cell lines, and seven cervical cancer cell lines). The data demonstrate that loss-of-inactive X in the female-derived cancer cells is mainly achieved by loss of an inactive X chromosomes followed by multiplication of an identical active X chromosomes. However, distinctive pathways, including reactivation of an inactive X chromosome, are also involved in the mechanisms for loss-of-inactive X and gain-of-active X in female-derived cancer cells. The biological significance of the loss-of-inactive X and gain-of-active X in the oncogenesis of Klinefelter syndrome and female-derived cancer cells are discussed.


Assuntos
Cromossomos Humanos X , Síndrome de Klinefelter/genética , Neoplasias/genética , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Metilação de DNA , Mecanismo Genético de Compensação de Dose , Feminino , Genes p53 , Humanos , Síndrome de Klinefelter/complicações , Masculino , Neoplasias/metabolismo , Neoplasias Ovarianas/genética , Polimorfismo Genético , RNA Longo não Codificante , RNA não Traduzido/metabolismo , Neoplasias do Colo do Útero/genética
18.
Lancet ; 363(9402): 40-2, 2004 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-14723995

RESUMO

Testicular germ-cell tumours (TGCTs) are the most common malignant diseases among men aged 20-40 years. We developed a DNA tumour marker for TGCTs based on the unmethylated DNA profile of a neoplasm. The 5' end of the XIST gene is mainly hypomethylated in TGCTs irrespective of XIST expression. Male somatic cells, however, show complete methylation through the CpG sites, including the minimum promoter and XIST-conserved repeats. Identification of a XIST unmethylated fragment in male plasma might be diagnostic for TGCTs.


Assuntos
Germinoma/diagnóstico , Germinoma/genética , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/genética , Biomarcadores Tumorais/sangue , Cromossomos Humanos X/genética , Cromossomos Humanos X/metabolismo , Metilação de DNA , DNA de Neoplasias/análise , DNA de Neoplasias/sangue , DNA de Neoplasias/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Germinoma/sangue , Humanos , Masculino , Metilação , RNA Longo não Codificante , RNA não Traduzido/sangue , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Neoplasias Testiculares/sangue
19.
Oncol Lett ; 10(2): 661-666, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26622550

RESUMO

Dimethyl sulfoxide (DMSO) is an amphipathic molecule that is used as a solvent in biological studies and as a vehicle for drug therapy. The present study was designed to evaluate the potential effects of DMSO as a solvent in the treatment of testicular embryonal carcinomas (ECs). DMSO was applied to two human EC cell lines (NEC8 and NEC14), with the treated cells evaluated in relation to cisplatin (CDDP) resistance, differentiation (using Vimentin, Fibronectin, TRA-1-60, and SSEA-1 and -3 as markers) and stemness (denoted by expression of SOX2 and OCT3/4). Furthermore, DNA methyltransferase (DNMT-1, -3A and -3L) expression and methylation status were analyzed. DMSO induced resistance to CDDP, aberrant differentiation and reduction of stemness-related markers in each of the EC cell lines. The expression levels of DNMT-3L and -3A were reduced in response to DMSO, while this treatment also affected DNA methylation. The data demonstrated that DMSO perturbed differentiation, reduced stemness and induced resistance to CDDP in human EC cells. Therefore, DMSO could reduce drug efficacy against EC cells and its use should be carefully managed in the clinical application of chemotherapy.

20.
Clin Genitourin Cancer ; 13(4): 350-358, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25701374

RESUMO

BACKGROUND: Sunitinib has been approved for the treatment of metastatic renal cell carcinoma (RCC). Sunitinib pharmacokinetics shows a large interpatient variability. PATIENTS AND METHODS: A retrospective, observational clinical study of 21 patients with RCC was performed. Sunitinib was administered for 4 weeks of a 6-week cycle for the first cycle. We evaluated the association of sunitinib-induced toxicities and clinical outcomes with the trough total sunitinib concentration in a steady state during the first cycle. RESULTS: The median total sunitinib concentration was 91.8 ng/mL (range, 49.8-205 ng/mL). There was an association between total sunitinib concentration and the severity of thrombocytopenia, anorexia, and fatigue. Patients with ≥ 100 ng/mL total sunitinib (n = 8), compared with patients with < 100 ng/mL (n = 13), had a greater incidence of Grade ≥ 3 toxicities (6 patients [75.0%] vs. 3 patients [23.1%]). Patients with < 100 ng/mL total sunitinib had significantly longer time to treatment failure (TTF) and progression-free survival (PFS) time than patients with ≥ 100 ng/mL (median TTF, 590 vs. 71 days; P = .04; median PFS, 748 vs. 238 days; P = .02). CONCLUSION: Results of this study suggest that therapeutic drug monitoring of sunitinib could be useful for avoiding severe toxicities. Dose reduction might be needed, especially when the total sunitinib concentration is ≥ 100 ng/mL, to avoid unnecessary early discontinuation of treatment.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Carcinoma de Células Renais/tratamento farmacológico , Indóis/efeitos adversos , Neoplasias Renais/tratamento farmacológico , Pirróis/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/farmacocinética , Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/mortalidade , Intervalo Livre de Doença , Feminino , Frequência do Gene , Humanos , Indóis/farmacocinética , Indóis/uso terapêutico , Estimativa de Kaplan-Meier , Neoplasias Renais/genética , Neoplasias Renais/mortalidade , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Pirróis/farmacocinética , Pirróis/uso terapêutico , Estudos Retrospectivos , Sunitinibe , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
Detalhe da pesquisa