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1.
J Cancer Res Clin Oncol ; 146(2): 449-455, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31838576

RESUMO

PURPOSE: Outcomes of multiply relapsed, refractory germ-cell tumour (GCT) patients remain poor with an overall survival (OS) of a few months only. Thus, new therapeutic advances are urgently needed. Cabazitaxel has shown preclinical activity in platinum-resistant GCT models. Here, we report the first clinical case series of cabazitaxel treatment for platinum-refractory GCT. METHODS: Data of multiply relapsed GCT patients receiving single-agent cabazitaxel were retrospectively analysed. Endpoints included 12-week progression-free survival (PFS) rate, disease control rate, tumour marker responses, median PFS and OS, and toxicity. RESULTS: Cabazitaxel showed limited activity in 13 heavily pre-treated GCT patients. After a median follow-up of 23 weeks (IQR 29), 69% of patients were deceased. A median of 2 cycles of cabazitaxel (range 1-7) were applied. The 12-week PFS rate was 31%. Median PFS and OS were 7 and 23 weeks, respectively. Two patients achieved objective responses (15%), three patients (23%) achieved a tumour marker decline ≥ 50%, and the disease control rate was 39%. Cabazitaxel was well tolerated. CTCAE° III-IV haemato-toxicity was most common (54%), and dose reductions were scarce (15%). CONCLUSION: In this case series, cabazitaxel showed limited activity in heavily pre-treated GCT patients. Two-phase II studies are underway (NCT02115165, NCT02478502) prospectively assessing cabazitaxel in multiply relapsed GCTs.


Assuntos
Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Taxoides/uso terapêutico , Neoplasias Testiculares/tratamento farmacológico , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Masculino , Neoplasias do Mediastino/tratamento farmacológico , Neoplasias do Mediastino/patologia , Metástase Neoplásica , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Retroperitoneais/tratamento farmacológico , Neoplasias Retroperitoneais/patologia , Estudos Retrospectivos , Taxoides/efeitos adversos , Neoplasias Testiculares/patologia
2.
Bull Cancer ; 107(2): 215-223, 2020 Feb.
Artigo em Francês | MEDLINE | ID: mdl-31882267

RESUMO

A residual mass (RM) is an abnormal image with a transverse axis of more than 1cm trans that remains visible on the CT scan performed after chemotherapy for metastatic germ cell tumors. Their management depends on the histology of the initial tumor. In the case of a non-seminomatous germ cell tumor, all residual lesions must be resected if the tumor markers are negative. The surgery usually begins with a retroperitoneal lymphadenectomy. This lymphadenectomy is a programed regional surgery and not the only resection of visible masses. All RM must be resected, regardless of their location, and may require successive actions. In order to limit its morbidity, modifications on the extent of the lymphadenectomy and the use of minimally invasive approaches are proposed by some center. When the initial tumor is a pure seminoma the attitude is different: the decay of the masses in post chemotherapy is often postponed. If lesions less than 3cm can be monitored, the others benefit from 18FDG PET at the end of chemotherapy: a positive attachment to PET is suspected of the presence of residual active tissue. The surgery of these RM is curative. If its extent is precise in the case of non-seminomatous tumor, it is more controversial in the case of seminoma. In the case of residual markers, surgery has a place in very specific situations.


Assuntos
Excisão de Linfonodo , Neoplasias Embrionárias de Células Germinativas/cirurgia , Seminoma/cirurgia , Neoplasias Testiculares/cirurgia , Biomarcadores Tumorais , Fluordesoxiglucose F18 , Humanos , Masculino , Neoplasia Residual , Neoplasias Embrionárias de Células Germinativas/diagnóstico por imagem , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Compostos Radiofarmacêuticos , Seminoma/diagnóstico por imagem , Seminoma/tratamento farmacológico , Neoplasias Testiculares/diagnóstico por imagem , Neoplasias Testiculares/tratamento farmacológico
3.
PLoS Med ; 16(11): e1002960, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31714912

RESUMO

BACKGROUND: Young male cancer survivors have lower testosterone levels, higher fat mass, and worse quality of life (QoL) than age-matched healthy controls. Low testosterone in cancer survivors can be due to orchidectomy or effects of chemotherapy and radiotherapy. We have undertaken a double-blind, placebo-controlled, 6-month trial of testosterone replacement in young male cancer survivors with borderline low testosterone (7-12 nmol/l). METHODS AND FINDINGS: This was a multicentre United Kingdom study conducted in secondary care hospital outpatients. Male survivors of testicular cancer, lymphoma, and leukaemia aged 25-50 years with morning total serum testosterone 7-12 nmol/l were recruited. A total of 136 men were randomised between July 2012 and February 2015 (42.6% aged 25-37 years, 57.4% 38-50 years, 88% testicular cancer, 10% lymphoma, matched for body mass index [BMI]). Participants were randomised 1:1 to receive testosterone (Tostran 2% gel) or placebo for 26 weeks. A dose titration was performed after 2 weeks. The coprimary end points were trunk fat mass and SF36 Physical Functioning score (SF36-PF) at 26 weeks by intention to treat. At 26 weeks, testosterone treatment compared with placebo was associated with decreased trunk fat mass (-0.9 kg, 95% CI -1.6 to -0.3, p = 0.0073), decreased whole-body fat mass (-1.8 kg, 95% CI -2.9 to -0.7, p = 0.0016), and increased lean body mass (1.5 kg, 95% CI 0.9-2.1, p < 0.001). Decrease in fat mass was greatest in those with a high truncal fat mass at baseline. There was no treatment effect on SF36-PF or any other QoL scores. Testosterone treatment was well tolerated. The limitations of our study were as follows: a relatively short duration of treatment, only three cancer groups included, and no hard end point data such as cardiovascular events. CONCLUSIONS: In young male cancer survivors with low-normal morning total serum testosterone, replacement with testosterone is associated with an improvement in body composition. TRIAL REGISTRATION: ISRCTN: 70274195, EudraCT: 2011-000677-31.


Assuntos
Neoplasias Testiculares/tratamento farmacológico , Testosterona/farmacologia , Testosterona/uso terapêutico , Tecido Adiposo/efeitos dos fármacos , Adulto , Composição Corporal/efeitos dos fármacos , Sobreviventes de Câncer , Método Duplo-Cego , Humanos , Leucemia/complicações , Linfoma/complicações , Masculino , Pessoa de Meia-Idade , Efeito Placebo , Qualidade de Vida , Neoplasias Testiculares/complicações , Reino Unido
4.
Crit Rev Oncol Hematol ; 143: 130-138, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31634730

RESUMO

Germ cell tumors (GCTs) are the most common type of solid tumor amongst patients between 15 and 35 years of age. They are also one of the types of tumor with the highest cure rate, due to their high sensitivity to cisplatin based chemotherapy. Nonetheless, around 15-20% of metastatic patients will not have curative options after a relapse on the first and second line. This proves that new therapeutic options for these refractory GCTs patients need to be developed. This article offers a bibliographic review of all studies using targeted treatment or immunotherapy for refractory GCTs patients.


Assuntos
Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Adolescente , Adulto , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cisplatino/administração & dosagem , Humanos , Masculino , Terapia de Alvo Molecular , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias Embrionárias de Células Germinativas/patologia , Seminoma/tratamento farmacológico , Seminoma/patologia , Teratoma/tratamento farmacológico , Teratoma/patologia , Neoplasias Testiculares/patologia , Adulto Jovem
5.
Anticancer Res ; 39(10): 5589-5596, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570454

RESUMO

BACKGROUND/AIM: To quantify the prognostic impact of age on relapse and mortality in patients with metastatic testicular germ cell tumors (TGCT). PATIENTS AND METHODS: Electronical medical records of 1,225 TGCT patients who were treated at a single academic center between 1994 and 2015 were reviewed. RESULTS: Higher age did not predict for worse progression-free survival (PFS) or for higher progression risk. The corresponding 5-year PFS estimates were 85% in patients younger than 40 years and 83% in the elderly population. Although not statistically significant, higher age was numerically associated with worse overall survival (OS) (univariate HR per five years increase in age=1.18, 95%CI=0.99-1.41). This was explained in regression analysis where age predicted for significantly higher risk of treatment-related death (p=0.022). CONCLUSION: Elderly patients with metastatic TGCT can achieve high cure rates similar to younger patients if they tolerate risk-adapted chemotherapy.


Assuntos
Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/patologia , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia , Adulto , Fatores Etários , Progressão da Doença , Humanos , Masculino , Prognóstico , Intervalo Livre de Progressão , Recidiva , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
6.
J Cancer Res Clin Oncol ; 145(12): 3037-3045, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31646373

RESUMO

INTRODUCTION: Because spermatocytic tumors of the testis are rare, only limited evidence exists regarding the malignant potential and the optimal management of localized and metastatic disease. MATERIALS AND METHODS: We performed a systematic review through MEDLINE, EMBASE, Scopus, Cochrane Database of Systematic Reviews and Web of Science to identify reports including patients with testicular spermatocytic tumors. RESULTS: From originally 7863 studies, we extracted data of 146 patients of which 99% were treated with radical orchiectomy. Metastases in patients with initially localised disease were diagnosed in 7% of patients and detected after a median follow-up of 5.5 months (range 2-21 months). Patients with aggressive histology (sarcoma or anaplastic subtype) were more likely to have metastatic disease (6/124 (5%) vs 9/22 (41%), p < 0.001). Patients with metastatic disease had larger primary tumors (92.5 vs 67.5 mm, p = 0.05). Life expectancy in patients with metastatic disease ranged from 1 to 25 months. CONCLUSION: The published literature does neither support the use of testis sparing surgery nor adjuvant therapy. Patients with aggressive variants or larger tumors were more likely to have metastases and develop recurrences within the first few years. Patients with metastatic disease have a limited life expectancy and metastatic spermatocytic tumors are not as responsive to chemotherapy as germ cell cancers.


Assuntos
Metástase Neoplásica/tratamento farmacológico , Espermatócitos/efeitos dos fármacos , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/cirurgia , Testículo/efeitos dos fármacos , Testículo/cirurgia , Humanos , Masculino , Neoplasias Primárias Múltiplas/tratamento farmacológico , Neoplasias Primárias Múltiplas/cirurgia , Resultado do Tratamento
7.
Hinyokika Kiyo ; 65(8): 347-350, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31501405

RESUMO

We present a case of unclassified sex cord-stromal testicular tumor with lung metastasis. A 48-year-old man consulted our hospital for left testicular enlargement that began 3 years ago. Computed tomography revealed a heterogeneously enhanced left testicular tumor 11 cm in diameter and a 5 mm metastatic lung tumor. The human chorionic gonadotropin (hCG) level was elevated (141.6 mU/ml), whereas the levels of α-fetoprotein (AFP) and LDH were normal. The external genitalia were normal and gynecomastia was not observed. Left high orchiectomy followed by 3 cycles of BEP chemotherapy (bleomycin, etoposide, and cisplatin) every 4 weeks was performed. The pathology of the excised specimen was unclassified sex cordstromal testicular tumor containing hCG-positive cells. On immunohistochemistry, the tumor cells were partly positive for AE1/AE3, hCG, and calretinin. Vimentin was diffusely positive, but OCT3/4, SALL4, GATA3, and CK7 were negative. After BEP treatment, the metastatic lung lesion disappeared. Unclassified sex cord-stromal testicular tumor is a rare disease and its treatment has not been established. Thus, further accumulation of cases is needed.


Assuntos
Tumores do Estroma Gonadal e dos Cordões Sexuais , Neoplasias Testiculares , Protocolos de Quimioterapia Combinada Antineoplásica/provisão & distribução , Bleomicina , Gonadotropina Coriônica/sangue , Cisplatino , Etoposídeo , Humanos , Masculino , Pessoa de Meia-Idade , Orquiectomia , Tumores do Estroma Gonadal e dos Cordões Sexuais/diagnóstico , Tumores do Estroma Gonadal e dos Cordões Sexuais/tratamento farmacológico , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/tratamento farmacológico
8.
J Cancer Res Clin Oncol ; 145(9): 2335-2342, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31286241

RESUMO

PURPOSE: Clinical stage (CS) 1 testicular seminoma is cured in almost 100% of cases following either retroperitoneal radiotherapy, carboplatin monotherapy, or surveillance strategies. Little is known about potential long-term effects of carboplatin. We, therefore, examined late sequelae of this drug in seminoma patients. PATIENTS AND METHODS: We retrospectively identified 451 patients with CS1 testicular seminoma treated between 1994 and 2014, of whom 243 underwent carboplatin therapy [median follow-up (F/U) 96 months], 81 received radiotherapy (median F/U 142 months), and 127 underwent surveillance (median F/U 40 months). Satisfaction regarding management, as well as the following events during F/U, were analysed by questionnaire: subsequent malignant neoplasms (SMNs), cardiovascular events, arterial hypertension, peptic ulcer, tinnitus, peripheral neuropathy, hypogonadism, and infertility. The relative frequencies of the events were analysed using descriptive statistics. The frequency of observed SMNs was compared with the expected number. RESULTS: Patients receiving carboplatin tolerated the treatment less well (71.2%) than those under surveillance (81.9%). After carboplatin, 12 SMNs (5.0%) were noted vis-a-vis 5.0 expected. There were three cases of prostatic cancer and 3 melanomas among the SMNs. Half of these SMNs occurred early after treatment. Among the other health events, only reported hypogonadism (13.2%) appeared to be marginally increased in frequency. CONCLUSIONS: This study found a 2.4-fold higher than expected rate of SMN-and a slightly increased rate of hypogonadism-in the long-term period following carboplatin treatment. Although further studies are needed to confirm these preliminary findings, these results are probably informative for clinicians caring for seminoma patients.


Assuntos
Carboplatina/administração & dosagem , Seminoma/tratamento farmacológico , Seminoma/radioterapia , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/radioterapia , Adolescente , Adulto , Idoso , Carboplatina/efeitos adversos , Quimioterapia Adjuvante , Terapia Combinada , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Humanos , Transtornos de Início Tardio/induzido quimicamente , Transtornos de Início Tardio/epidemiologia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Segunda Neoplasia Primária/epidemiologia , Radioterapia Adjuvante , Estudos Retrospectivos , Seminoma/patologia , Neoplasias Testiculares/patologia , Resultado do Tratamento , Conduta Expectante , Adulto Jovem
9.
Urol Clin North Am ; 46(3): 333-339, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31277728

RESUMO

In any man with a solid testicular mass, cancer should be considered until proven otherwise. Radical inguinal orchiectomy is the treatment of choice in patients with testis mass. Placement of a testicular prosthesis is safe with a very low complication rate and should be offered to all patients undergoing radical orchiectomy. In patients with widespread or life-threatening advanced disease, delayed orchiectomy following chemotherapy is recommended. Testis-sparing surgery can be performed in highly selected patients with solitary testicle mass, bilateral testicular tumors, or strong suspicion of a benign lesion.


Assuntos
Neoplasias Testiculares/cirurgia , Humanos , Masculino , Orquiectomia , Tratamentos com Preservação do Órgão , Próteses e Implantes , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/patologia
10.
Urol Clin North Am ; 46(3): 377-388, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31277732

RESUMO

The modern treatment of disseminated germ cell tumors (GCT) relies largely on cisplatin-based regimens, particularly combination chemotherapy with bleomycin, etoposide, and cisplatin. This article reviews the evidence supporting its use as well as common alterations based on prognostic grouping or contraindications to bleomycin. Special topics around the management of intermediate/poor prognosis choriocarcinoma and brain metastases are included. The management of residual masses for both seminoma and nonseminoma is discussed as well as long-term follow-up care of patients. Finally, the management of relapsed disseminated GCT is addressed.


Assuntos
Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores Tumorais/análise , Bleomicina/administração & dosagem , Cisplatino/administração & dosagem , Etoposídeo/administração & dosagem , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/patologia , Guias de Prática Clínica como Assunto , Prognóstico , Neoplasias Testiculares/patologia
11.
Urol Clin North Am ; 46(3): 389-398, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31277733

RESUMO

The introduction of cisplatin-based chemotherapy has revolutionized the care of patients with disseminated testicular germ cell tumors. Although a majority are cured with chemotherapy alone, surgical resection continues to play a role because one-third will have residual mass after chemotherapy. In this article, we review the current indications for postchemotherapy resection in nonseminomatous germ cell tumors, including masses greater than 1 cm, resection after salvage chemotherapy, with elevated markers, after late relapse, and for growing teratoma syndrome. We also highlight technical considerations of this often-challenging surgery, including the need for adjunctive procedures, extraretroperitoneal resections, and modern techniques to minimize morbidity.


Assuntos
Neoplasia Residual/cirurgia , Neoplasias Embrionárias de Células Germinativas/cirurgia , Neoplasias Testiculares/cirurgia , Biomarcadores Tumorais/análise , Intervalo Livre de Doença , Humanos , Laparoscopia/métodos , Excisão de Linfonodo , Metástase Linfática/patologia , Masculino , Neoplasia Residual/tratamento farmacológico , Neoplasia Residual/patologia , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Procedimentos Cirúrgicos Robóticos , Terapia de Salvação , Neoplasias Testiculares/tratamento farmacológico
13.
Intern Med ; 58(22): 3277-3282, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31327829

RESUMO

A 69-year-old man who had undergone chemoradiotherapy for advanced pulmonary adenocarcinoma had bilateral testicular and adrenal gland masses on a routine follow-up examination. We performed left orchiectomy, and the histopathological examination confirmed metastatic pulmonary adenocarcinoma involving the extracted testis. He was treated for disease progression with nivolumab after unsuccessful cytotoxic chemotherapy, which resulted in regression of recurrent adrenal and right testicular tumors. We reviewed the existing literature on metastatic testicular tumors and found that testicular metastasis from lung cancer is rare and poses a chemotherapeutic challenge. Based on our experience, immune checkpoint inhibitors seem to have good efficacy for treating testicular metastasis.


Assuntos
Adenocarcinoma de Pulmão/patologia , Antineoplásicos Imunológicos/uso terapêutico , Neoplasias Pulmonares/patologia , Nivolumabe/uso terapêutico , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/secundário , Adenocarcinoma de Pulmão/terapia , Idoso , Humanos , Neoplasias Pulmonares/terapia , Masculino , Orquiectomia
14.
Biomed Res Int ; 2019: 5030349, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275973

RESUMO

Introduction: Although serum tumor markers beta human chorionic gonadotropin (bHCG), alpha-fetoprotein (AFP), and lactate dehydrogenase (LDH) are well-established tools for the management of testicular germ cell tumours (GCTs), there are only few data from contemporary cohorts of primary GCT patients regarding these biomarkers. Our aim was to evaluate marker elevations in testicular GCTs and to document their associations with various clinical characteristics. Patients and Methods: A total of 422 consecutive patients with GCTs were retrospectively analysed regarding serum levels of bHCG, AFP, and LDH during the course of treatment. Additionally, the following characteristics were recorded: histology, age, laterality, clinical stage (CS), pT-stage, and tumour size. Marker elevations were first tabulated in dichotomized way (elevated: yes/no) in various subgroups and second as continuous measured serum values. Descriptive statistical methods were employed to look for differences among subgroups and for associations of elevations with clinical parameters. Results: In all GCT patients, the frequencies of elevated levels of bHCG, AFP, LDH, and bHCG or AFP were 37.9%, 25.6%, 32.9%, and 47.6%; in pure seminomas 28%, 2.8%, 29.1%, and 30.3%; and in nonseminoma 53.0%, 60.1%, 38.7%, and 73.8%. Significant associations were noted with pT-stages >pT1, clinical stages >CS1, tumour size, and younger age. Frequencies of marker elevations dropped significantly after treatment, but LDH levels remained elevated in 30.5%-34.1%. Relapsing patients (n=27) had elevated levels of bHCG, AFP, and LDH in 25.9%, 22.2%, and 29.6%, respectively, thirteen of whom with a changed marker pattern. Conclusions: The classical GCT-biomarkers correlate with treatment success. Clinical utility is limited due to proportions of < 50% of patients with elevated levels and the low specificity of LDH. The elevation rates are significantly associated with histology, clinical and pT-stages, tumour size, and younger age. Individual marker patterns may change upon relapse. Clinically, ideal biomarkers are yet to be found.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Embrionárias de Células Germinativas/sangue , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Testiculares/sangue , Neoplasias Testiculares/tratamento farmacológico , Fatores Etários , Gonadotropina Coriônica/sangue , Estudos de Coortes , Humanos , Masculino , Metástase Neoplásica , Recidiva Local de Neoplasia/sangue , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/patologia , Seminoma/sangue , Seminoma/diagnóstico , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/patologia , Resultado do Tratamento , Carga Tumoral , alfa-Fetoproteínas/metabolismo
15.
Biomed Pharmacother ; 117: 109090, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31202174

RESUMO

Pannexin (Panx) plays a crucial role in several cellular processes such as immune cell death, cell proliferation, invasion, and migration, apoptosis, and autophagy. However, the role of Panx in regulating cell migration and invasion in testicular cancer remains to be elucidated. In the present study, we determined the correlation between Panx-1 channel function and migration and invasion in I-10 testicular cancer cells. Transwell and wound healing assays showed that inhibition of Panx-1 by carbenoxolone (CBX) and probenecid (PBN) attenuated the migration and invasion of testicular cancer cells in vitro. Moreover, knockdown of Panx-1 with short hairpin RNA (shRNA) remarkably decreased the migration and invasion ability of I-10 cells. In shRNA-transfected cells, extracellular ATP (released through Panx channel) was also found to be decreased. Similarly, overexpression of Panx-1 with mPanx-1 increased the migration and invasion ability of I-10 cells. Moreover, we found that in mPanx-1-transfected cells treated with U0126 (inhibitor of p-ERK1/2), the migration and invasion of I-10 cells were remarkably attenuated. Overall, increased Panx-1 promotes migration and invasion in testicular cancer cells, and the effect is probably be related with ERK1/2 kinase activity. Thus, Panx-1 can serve as a potential therapeutic target for the treatment of testicular cancer.


Assuntos
Movimento Celular/genética , Conexinas/genética , Sistema de Sinalização das MAP Quinases/genética , Invasividade Neoplásica/genética , Neoplasias Embrionárias de Células Germinativas/genética , Proteínas do Tecido Nervoso/genética , Neoplasias Testiculares/genética , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Carbenoxolona/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Camundongos , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Probenecid/farmacologia , RNA Interferente Pequeno/genética , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Neoplasias Testiculares/tratamento farmacológico
16.
PLoS Med ; 16(6): e1002816, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31163029

RESUMO

BACKGROUND: Because of the potential mutagenic effects of chemo- and radiotherapy, there is concern regarding increased risk of congenital malformations (CMs) among children of fathers with cancer. Previous register studies indicate increased CM risk among children conceived after paternal cancer but lack data on oncological treatment. Increased CM risk was recently reported in children born before paternal cancer. This study aims to investigate whether anti-neoplastic treatment for testicular germ-cell cancer (TGCC) implies additional CM risk. METHODS AND FINDINGS: In this nationwide register study, all singletons born in Sweden 1994-2014 (n = 2,027,997) were included. Paternal TGCC diagnoses (n = 2,380), anti-neoplastic treatment, and offspring CMs were gathered from the Swedish Norwegian Testicular Cancer Group (SWENOTECA) and the Swedish Medical Birth Register. Children were grouped based on +/- paternal TGCC; treatment regimen: surveillance (n = 1,340), chemotherapy (n = 2,533), or radiotherapy (n = 360); and according to time of conception: pre- (n = 2,770) or post-treatment (n = 1,437). Odds ratios (ORs) for CMs were calculated using logistic regression with adjustment for parental ages, maternal body mass index (BMI), and maternal smoking. Children conceived before a specific treatment acted as reference for children conceived after the same treatment. Among children fathered by men with TGCC (n = 4,207), 184 had a CM. The risk of malformations was higher among children of fathers with TGCC compared with children fathered by men without TGCC (OR 1.28, 95% confidence interval [CI] 1.19-1.38, p = 0.001, 4.4% versus 3.5%). However, no additional risk increase was associated with oncological treatment when comparing post-treatment-to pretreatment-conceived children (chemotherapy, OR = 0.82, 95% CI 0.54-1.25, p = 0.37, 4.1% versus 4.6%; radiotherapy, OR = 1.01, 95% CI 0.25-4.12, p = 0.98, 3.2% versus 3.0%). Study limitations include lack of data on use of cryopreserved or donor sperm and on seminoma patients for the period 1995-2000-both tending to decrease the difference between the groups with TGCC and without TGCC. Furthermore, the power of analyses on chemotherapy intensity and radiotherapy was limited. CONCLUSIONS: No additional increased risk of CMs was observed in children of men with TGCC treated with radio- or chemotherapy. However, paternal TGCC per se was associated with modestly increased risk for offspring malformations. Clinically, this information can reassure concerned patients.


Assuntos
Antineoplásicos/efeitos adversos , Pai , Neoplasias Embrionárias de Células Germinativas/epidemiologia , Neoplasias Embrionárias de Células Germinativas/radioterapia , Malformações do Sistema Nervoso/epidemiologia , Sistema de Registros , Neoplasias Testiculares/epidemiologia , Neoplasias Testiculares/radioterapia , Anormalidades Induzidas por Radiação/diagnóstico , Anormalidades Induzidas por Radiação/epidemiologia , Adulto , Criança , Feminino , Humanos , Masculino , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Malformações do Sistema Nervoso/induzido quimicamente , Malformações do Sistema Nervoso/diagnóstico , Suécia/epidemiologia , Neoplasias Testiculares/tratamento farmacológico
17.
Bull Cancer ; 106(9): 805-811, 2019 Sep.
Artigo em Francês | MEDLINE | ID: mdl-31171345

RESUMO

Testicular cancers are the most frequent and the most curable cancers in young men. Treatments of these cancers represent a great success with cure rate over to 95 %. However, chemotherapy side effects may occur during or after several years post-treatment. This review aimed to highlight complications and physical and psychological side effects occurring mainly after chemotherapy treatment for testicular cancer, and to propose a personalized post-cancer plan specific for patients treated for testicular cancer. Treatments of these cancers can cause short-term complications (asthenia, nausea, vomiting, alopecia..). These side effects disappear within a few months after the end of the treatments. Late complications may occur several years post-treatment. Cardiovascular disease, metabolic syndrome and secondary neoplasia represent the most severe late effects among patients treated for testicular cancer. Given the increased incidence of these chemotherapy-induced side effects, it is indispensable to establish a specific follow up which must include a particular vigilance on the risk of occurrence of second cancer, a follow-up of the cardio-vascular risk factors, pulmonary and auditory follow-up, and early detection of psychosocial disorders.


Assuntos
Antineoplásicos/efeitos adversos , Neoplasias Testiculares/tratamento farmacológico , Doenças Cardiovasculares/induzido quimicamente , Cognição/efeitos dos fármacos , Transtornos Cognitivos/induzido quimicamente , Síndrome de Fadiga Crônica/induzido quimicamente , Fertilidade/efeitos dos fármacos , Seguimentos , Humanos , Infertilidade Masculina/induzido quimicamente , Infertilidade Masculina/prevenção & controle , Pneumopatias/induzido quimicamente , Masculino , Síndrome Metabólica/induzido quimicamente , Segunda Neoplasia Primária/induzido quimicamente , Doenças do Sistema Nervoso/induzido quimicamente , Neoplasias Testiculares/psicologia , Fatores de Tempo
18.
BMC Surg ; 19(1): 62, 2019 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-31200669

RESUMO

BACKGROUND: Tumor lysis syndrome is an unusual metabolic emergency in solid tumors. Perioperative occurrence of this syndrome is extremely rare but may have fatal consequences if not detected and treated on time. CASE REPORT: We report a 19-year patient with testicular germ cell tumor after first line chemotherapy with giant growing teratoma syndrome in retroperitoneum. He underwent radical resection, however, perioperatively, a fatal case of heart failure due to unrecognized intraoperative tumor lysis syndrome developed. CONCLUSION: Surgeons, anesthesiologists and oncologists should be aware of this complication in order to be prepared for such an emergency.


Assuntos
Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Retroperitoneais/cirurgia , Teratoma/cirurgia , Neoplasias Testiculares/tratamento farmacológico , Síndrome de Lise Tumoral/etiologia , Cisplatino/administração & dosagem , Humanos , Neoplasias Pulmonares/cirurgia , Metástase Linfática , Masculino , Orquiectomia , Prognóstico , Espaço Retroperitoneal , Adulto Jovem
19.
Transplant Proc ; 51(4): 1293-1295, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31101217

RESUMO

BACKGROUND: Cystic fibrosis (CF) is one of the most common genetic disorders that develops from a mutation of the cystic fibrosis transmembrane regulator gene. Patients with CF are known to be at risk for malignancies, and lung transplantation-associated immunosuppression further increases this risk. CASE REPORT: We describe a case of a 29-year-old male patient with CF who developed testicular cancer 14 months after a lung transplantation. Immunosuppressive therapy included antithymocyte globulin induction and tacrolimus, mycophenolate, and prednisolone maintenance therapy as compared to standard alemtuzumab induction, followed by tacrolimus and prednisolone, as used in our center. He underwent semicastration and refused chemotherapy. Immunosuppressive treatment was changed to tacrolimus, everolimus, and prednisolone, which did not influence excellent graft function. This case report highlights the importance of uro-oncological observation of patients with CF following lung transplantations.


Assuntos
Fibrose Cística/cirurgia , Imunossupressão/efeitos adversos , Transplante de Pulmão , Neoplasias Embrionárias de Células Germinativas/imunologia , Neoplasias Testiculares/imunologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Humanos , Imunossupressores/efeitos adversos , Transplante de Pulmão/efeitos adversos , Masculino , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico
20.
Genes (Basel) ; 10(5)2019 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-31083486

RESUMO

Although previous research identified candidate genetic polymorphisms associated with cisplatin nephrotoxicity, varying outcome definitions potentially contributed to the variability in the effect size and direction of this relationship. We selected genetic variants that have been significantly associated with cisplatin-induced nephrotoxicity in more than one published study (SLC22A2 rs316019; ERCC1 rs11615 and rs3212986; ERCC2 rs1799793 and rs13181) and performed a replication analysis to confirm associations between these genetic polymorphisms and cisplatin nephrotoxicity using various outcome definitions. We included 282 germ cell testicular cancer patients treated with cisplatin from 2009-2014, aged >17 years recruited by the Canadian Pharmacogenomics Network for Drug Safety. Nephrotoxicity was defined using four grading tools: (1) Common Terminology Criteria for Adverse Events (CTCAE) v4.03 for acute kidney injury (AKI) or CTCAE-AKI; (2) adjusted cisplatin-induced AKI; (3) elevation of serum creatinine; and (4) reduction in the estimated glomerular filtration rate (eGFR). Significant associations were only found when using the CTCAE v4.03 definition: genotype CA of the ERCC1 rs3212986 was associated with decreased risk of cisplatin nephrotoxicity (ORadj = 0.24; 95% CI:0.08-0.70; p = 0.009) compared to genotype CC. In contrast, addition of allele A at SLC22A2 rs316019 was associated with increased risk (ORadj = 4.41; 95% CI:1.96-9.88; p < 0.001) while genotype AC was associated with a higher risk of cisplatin nephrotoxicity (ORadj = 5.06; 95% CI:1.69-15.16; p = 0.004) compared to genotype CC. Our study showed that different case definitions led to variability in the genetic risk ascertainment of cisplatin nephrotoxicity. Therefore, consensus on a set of clinically relevant outcome definitions that all such studies should follow is needed.


Assuntos
Lesão Renal Aguda/induzido quimicamente , Cisplatino/efeitos adversos , Proteínas de Ligação a DNA/genética , Endonucleases/genética , Transportador 2 de Cátion Orgânico/genética , Neoplasias Testiculares/tratamento farmacológico , Neoplasias Testiculares/genética , Proteína Grupo D do Xeroderma Pigmentoso/genética , Lesão Renal Aguda/genética , Adulto , Biomarcadores Farmacológicos , Creatinina/sangue , Proteínas de Ligação a DNA/metabolismo , Endonucleases/metabolismo , Frequência do Gene , Taxa de Filtração Glomerular/efeitos dos fármacos , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/tratamento farmacológico , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/metabolismo , Transportador 2 de Cátion Orgânico/metabolismo , Farmacogenética , Polimorfismo Genético , Estudos Retrospectivos , Neoplasias Testiculares/metabolismo , Proteína Grupo D do Xeroderma Pigmentoso/metabolismo
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