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1.
Int J Gynecol Cancer ; 33(9): 1376-1382, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37524495

RESUMO

OBJECTIVE: To evaluate the prognosis and recurrence in patients with residual lesions of pulmonary metastasis from gestational trophoblastic neoplasia after initial treatment, and to explore the clinical significance of pulmonary resection. METHODS: A retrospective analysis was performed on 606 patients with residual lesions from pulmonary metastasis after receiving standardized chemotherapy as initial treatment in Peking Union Medical College Hospital from January 2002 to December 2018. Patients were divided into surgery (51 patients) and non-surgery (555 patients) groups. The prognosis of these patients was compared. Risk factors affecting recurrence were analyzed to explore the effect of pulmonary resection. RESULTS: Among low risk patients, complete remission rate was 100% and recurrence rate was <1% in both groups. Among high risk patients, complete remission and recurrence rates were 93.5% and 10.3% in the surgery group and 94.7% and 14.3% in the non-surgery group, respectively. There was no significant difference in prognostic features between the two groups (all p>0.05). No significant difference was found in recurrence rates based on recurrence risk factors (≥3.2 cm residual lung lesions, prognosis score ≥9.0, and drug resistance) between the two groups (all p>0.05). CONCLUSION: After standardized chemotherapy, pulmonary resection was not necessary for initially treated stage III gestational trophoblastic neoplasia patients whose blood ß human chorionic gonadotropin levels normalized and residual lung lesions remained stable. These patients should be closely monitored during follow-up, regardless of the size of the residual lung lesions or high/low risk score, especially within a year after complete remission.


Assuntos
Doença Trofoblástica Gestacional , Neoplasias Pulmonares , Gravidez , Feminino , Humanos , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Doença Trofoblástica Gestacional/tratamento farmacológico , Doença Trofoblástica Gestacional/cirurgia , Doença Trofoblástica Gestacional/patologia , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico
2.
Adv Clin Exp Med ; 32(2): 195-202, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36482818

RESUMO

BACKGROUND: Serum beta-human chorionic gonadotropin (ß-hCG) is an important biomarker for the detection of ectopic pregnancies (EPs). The ß-hCG levels between days 1 and 4 after methotrexate (MTX) treatment as an indicator of the success of the MTX in EP have been the focus of research. OBJECTIVES: To determine whether the change in the ß-hCG levels at day 1 and 4 and pretreatment at 48-hour increments can predict early treatment failure of single-dose MTX in EP. MATERIAL AND METHODS: This was a retrospective study of 1120 EPs treated with a single dose of MTX. Treatment failure was defined as an obligation to proceed to surgery or the need for additional doses of MTX. RESULTS: A total 722 out of 1120 EPs had an increase in ß-hCG on day 4 after MTX treatment. The logistic regression analysis indicated that 3 dependents were significantly associated with treatment failure: 1) a pretreatment 48-hour increase in ß-hCG (odds ratio (OR): 1.249, 95% confidence interval (95% CI): 1.008-2.049, p < 0.001); 2) a change in ß-hCG between day 1 and 4 (OR: 1.384, 95% CI: 1.097-2.198, p < 0.001); and 3) a history of EP (OR: 1.208, 95% CI: 1.041- 2.011, p < 0.001). The optimal cutoff point for the prediction of treatment failure was an increase of more than 19% in the 48 h before the treatment, and an increase of more than 36% between day 1 and day 4 in ß-hCG concentrations. Patients with an increase in ß-hCG levels of less than 36% on day 4 experienced MTX treatment failure in 4.2% (n = 25), compared to 74.5% (n = 88) of the patients with an increase above 36%. CONCLUSIONS: A serum ß-hCG increase of more than 36% on day 4 after the administration of MTX alongside a more than 19% increase in ß-hCG concentration 48 h before the MTX treatment may predict the early failure of medical treatment for an EP.


Assuntos
Abortivos não Esteroides , Gravidez Ectópica , Gravidez , Feminino , Humanos , Metotrexato/uso terapêutico , Estudos Retrospectivos , Abortivos não Esteroides/uso terapêutico , Resultado do Tratamento , Gonadotropina Coriônica Humana Subunidade beta/análise , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico , Gravidez Ectópica/diagnóstico , Gravidez Ectópica/terapia
3.
Pan Afr Med J ; 41: 200, 2022.
Artigo em Francês | MEDLINE | ID: mdl-35685101

RESUMO

Introduction: the purpose of this study was to identify factors associated with the failure of medical treatment for ectopic pregnancy (EP) in women at the Yaoundé Gynaecology, Obstetrics and Pediatrics Hospital. Methods: we conducted a case-control study using a retrospective data collection over a 10-year period from January 1st 2008 to December 31st 2017. Our study included all patients treated for EP; the study group was composed of patients in whom medical treatment had been unsuccessful while the control group was composed of patients in whom medical treatment had been successful. The variables studied were: socio-demographic, clinical, paraclinical and therapeutic features. Consecutive and complete sampling were used. Multivariate analysis was performed. Results: we enrolled 92 patients, including 23 cases and 69 controls. The variables associated with the failure of medical treatment for EP after univariate analysis were: initial ß-HCG (beta-human chorionic gonadotropin) level > 10000IU/L (OR=3.05; P=0.031), ß-HCG level on day 4 > 10000IU/L (OR=7.15;P=0.000), ß-HCG level on day 7 > 10000UI/L (OR=20; P=0.000), Fernandez score ≥ 13 (OR=3.09;P=0.020), the presence of fetal heart activity (OR=2.8; P=0.036), a history of voluntary abortion (OR=2.67;P=0.043) and primary level of education. (P=0.013). After multivariate analysis, predictors were: initial ß-HCG level>10000 IU/L (OR=8.97; P=0.004), ß-HCG level on day 4>10000 IU/L (OR=8.44;P= 0.007), Fernandez score ≥ 13 (OR=1.12;P=0.005), and the presence of fetal heart activity (OR=6.09;P=0,026). Conclusion: at the Yaoundé Gynaecology, Obstetrics and Pediatrics Hospital predictors of failure of medical treatment for EP were related to initial ß-HCG level and fetal viability.


Assuntos
Gravidez Ectópica , Falha de Tratamento , Camarões , Estudos de Casos e Controles , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico , Feminino , Hospitais Pediátricos , Humanos , Metotrexato/uso terapêutico , Gravidez , Gravidez Ectópica/tratamento farmacológico , Estudos Retrospectivos
4.
Reprod Sci ; 29(4): 1209-1214, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35157263

RESUMO

To determine the predictors for tubal rupture among women treated with methotrexate (MTX) for ectopic pregnancy. We performed a retrospective cohort analysis in a tertiary university-affiliated medical center. Medical records of 401 women who were diagnosed with ectopic pregnancy and were treated with MTX between January 2001 and June 2017 were reviewed. Forty-one women were diagnosed with ruptured ectopic pregnancy (study group) and 360 women with non-ruptured ectopic pregnancy (control group). Descriptive data and predictive variables for rupture ectopic pregnancy following MTX treatment were reviewed. Out of 122 women who failed MTX treatment, forty-one women had tubal rupture (33.6%). The median time interval from MTX treatment to tubal rupture was 6 days (1-25). ß-hCG percentage change in the 48 h preceding MTX treatment and ß-hCG level at day 0 were independent predictors for tubal rupture (odds ratio [OR] = 1.08, 95% confidence interval [CI] = 1.04-1.12, p < 0.001 for every percent change in ß-hCG; OR = 1.001, 95% CI = 1.0003-1.002 for every unit change in ß-hCG, respectively). In a decision tree analysis model, in women with ß-hCG percentage increment >69% in the 48 h preceding methotrexate the probability for tubal rupture was 85%. Risk assessment for tubal rupture should be made before methotrexate treatment according to ß-hCG dynamics and level. The absolute risk for tubal rupture in women with ß-hCG increment<20% is low.


Assuntos
Abortivos não Esteroides , Gravidez Ectópica , Abortivos não Esteroides/efeitos adversos , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico , Aconselhamento , Feminino , Humanos , Masculino , Metotrexato/efeitos adversos , Gravidez , Gravidez Ectópica/tratamento farmacológico , Estudos Retrospectivos
5.
J Proteome Res ; 17(1): 276-289, 2018 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-29028349

RESUMO

Previously, we identified that ß-hCG is expressed by BRCA1 mutated but not wild type breast cancers in vitro/in vivo and exhibited a novel event in ß-hCG overexpressing BRCA1 mutated HCC1937 cells where the cells were able to form spheres (HCC1937 ß spheres) in adherent cell culture plates even in the absence of any growth factors. These spheres express stem cell and EMT markers. In the present study, we carried out the total proteomic profiling of these HCC1937 ß spheres obtained from BRCA1 defective ß-hCG expressing stable breast cancer cells to analyze the cell signaling pathways that are active in these cells. Functional annotation revealed proteins (164 cellular and 97 secretory) predominantly involved in oxygen binding, nucleosome assembly, cytoskeleton organization, protein folding, etc. Many of the proteins identified from HCC1937 ß spheres in this study are also up regulated in breast cancers, which are directly linked with poor prognosis in human cancer samples as analyzed using TCGA data set. Survival analysis shows that ß-hCG expressing cancer patients are linked with poor survival rate. Interestingly, hemoglobins were identified at both cellular and secretory level in HCC1937 ß spheres and experiments after treating with ROS inducers revealed that ß-hCG induces hemoglobin and protects the cancer cells during oxidative stress. Our proteomic data strongly propose ß-hCG as an oncogenic molecule associated with BRCA1 mutation, and hence, targeting ß-hCG could be a strategy to treat BRCA1 defective breast cancers.


Assuntos
Proteína BRCA1/genética , Gonadotropina Coriônica Humana Subunidade beta/farmacologia , Proteômica/métodos , Neoplasias de Mama Triplo Negativas/patologia , Linhagem Celular Tumoral , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico , Hemoglobinas/análise , Humanos , Mutação , Estresse Oxidativo , Prognóstico , Análise de Sobrevida
6.
J Pediatr Urol ; 7(2): 158-61, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20570565

RESUMO

OBJECTIVE: Androgens have a positive effect on penile growth in children, but they may also have a repressive effect on the healing process. The aim of this prospective study was to compare the outcomes of onlay urethroplasty with and without preoperative androgen stimulation in patients with severe hypospadias. PATIENTS AND METHOD: Of 300 severe hypospadias cases treated at a single institution, 126 operated on by the same surgeon had complete follow-up data, and 30 of these received preoperative androgen treatment (human chorionic gonadotrophin and/or systemic testosterone) 1-24 months before surgery. RESULTS: Thirty-five patients presented with a complication (27.7%) of whom 26 (20.6%) had a fistula or dehiscence. Among patients on androgen stimulation there was a 30% healing complication rate (9/30) whereas for those without this was 17.7% (17/96). When androgenic treatment was given > 3 months prior to surgery the healing complication rate was 21.7% (5/23), and when < 3 months prior to surgery the rate reached 57% (4/7). Mean follow up was 41 months (10-97). CONCLUSION: Although the numbers were too small in this series to reach statistical significance, the tissular interactions of androgens in the healing process reported by dermatologists should alert the hypospadiologists and lead to a further prospective study to define the optimal protocol for stimulation of the penis in specific cases without affecting outcome.


Assuntos
Androgênios/uso terapêutico , Hipospadia/tratamento farmacológico , Hipospadia/cirurgia , Testosterona/uso terapêutico , Cicatrização/efeitos dos fármacos , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico , Seguimentos , Humanos , Masculino , Projetos Piloto , Complicações Pós-Operatórias/prevenção & controle , Cuidados Pré-Operatórios , Estudos Retrospectivos
7.
Int Immunopharmacol ; 10(2): 230-8, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19913113

RESUMO

It has been demonstrated that the beta-subunit of human chorionic gonadotropin (beta-hCG) is ectopically expressed on a variety of human cancers of different histological types and has been used as an antigenic target in anti-cancer vaccines. We engineered a fusion protein by fusing 10 tandemly repeated copies of the 10-residue sequence of beta-hCG (109-118) (in CTP37) combined with beta-hCG C-terminal 37 peptides to mycobacterial heat-shock protein 65 and immunized mice via subcutaneous injection. Humoral immune and cellular immune responses were effectively elicited. High titer of anti-beta-hCG antibody was detected in immunized mice sera by ELISA and verified by Western blot analyses. The fusion protein of HSP65-X10-beta-hCGCTP37 effectively inhibited the growth of tumor both protective and therapeutic anti-tumor immunity in hepatocellular carcinoma tumor models in mice. Meanwhile, it also attenuated tumor-induced angiogenesis in intradermal tumor model in mice. Taken together, these results demonstrate that immune responses are effectively induced by a novel fusion protein vaccine targeting beta-hCG, suppressing the growth of hepatocellular carcinoma in mice. The beta-hCG-targeted vaccine holds promise for the treatment of a number of cancers and merits further study.


Assuntos
Proteínas de Bactérias/imunologia , Vacinas Anticâncer/imunologia , Carcinoma Hepatocelular/terapia , Chaperonina 60/imunologia , Gonadotropina Coriônica Humana Subunidade beta/imunologia , Neoplasias Hepáticas/terapia , Proteínas Recombinantes de Fusão/imunologia , Animais , Anticorpos Antineoplásicos/imunologia , Especificidade de Anticorpos/imunologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/uso terapêutico , Vacinas Anticâncer/genética , Vacinas Anticâncer/uso terapêutico , Carcinoma Hepatocelular/imunologia , Chaperonina 60/genética , Chaperonina 60/uso terapêutico , Gonadotropina Coriônica Humana Subunidade beta/genética , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico , Neoplasias Hepáticas/imunologia , Masculino , Camundongos , Neovascularização Patológica/imunologia , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/uso terapêutico , Sequências de Repetição em Tandem
8.
Endocr Relat Cancer ; 16(2): 549-64, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19261682

RESUMO

Lytic peptide Hecate (23-amino acid (AA)) fused with a 15-AA fragment of human chorionic gonadotropin-beta (CG-beta), Hecate-CGbeta conjugate (H-CGbeta-c) selectively binds to and destroys tumor cells expressing LH/chorionic gonadotropin receptor (Lhcgr). Transgenic mice (6.5 month old) expressing SV40 T-antigen under the inhibin-alpha promoter (inhalpha/Tag) presenting with Lhcgr expressing adrenal tumors were treated either with H-CGbeta-c, GnRH antagonist (GnRH-a), estradiol (E(2); only females) or their combinations for 1 month. We expected that GnRH-a or E(2) in combination with H-CGbeta-c could improve the treatment efficacy especially in females by decreasing circulating LH and eliminating the potential competition of serum LH with the H-CGbeta-c. GnRH-a and H-CGbeta-c treatments were successful in males (adrenal weights 14 +/- 2.8 mg and 60 +/- 26 vs 237 +/- 59 mg in controls; P < 0.05). Histopathologically, GnRH-a apparently destroyed the adrenal parenchyma leaving only the fibrotic capsule with few necrotic foci. In females, H-CGbeta-c was totally ineffective, whereas GnRH-a (19 +/- 5 mg) or E(2) (77 +/- 50 mg) significantly reduced the adrenal weights compared with controls (330 +/- 70 mg). Adrenal morphometry, cell proliferation markers, post-treatment suppression of serum progesterone, and quantitative RT-PCR of GATA-4, Lhcgr, and GATA-6 further supported the positive outcome. H-CGbeta-c selectively killed the Lhcgr expressing tumor cells, whereas GnRH-a blocked tumor progression through gonadotropin suppression, emphasizing the gonadotropin dependency of these adrenocortical tumors. If extrapolated to humans, H-CGbeta-c could be considered for the treatment of gonadotropin-dependent adrenal tumors in males, whereas in females gonadotropin suppression, but not H-CGbeta-c, would work better.


Assuntos
Neoplasias do Córtex Suprarrenal/tratamento farmacológico , Antígenos Virais de Tumores/metabolismo , Gonadotropinas/metabolismo , Inibinas/genética , Meliteno/análogos & derivados , Regiões Promotoras Genéticas/genética , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/patologia , Animais , Proliferação de Células , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico , Feminino , Hormônio Liberador de Gonadotropina/metabolismo , Humanos , Técnicas Imunoenzimáticas , Masculino , Meliteno/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Progesterona/sangue , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Vírus 40 dos Símios/genética
9.
Mol Cell Endocrinol ; 269(1-2): 17-25, 2007 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-17363137

RESUMO

Improvement of cancer treatment is a major challenge of medical research. Despite the immense efforts made in the improvement of diagnosis and treatment, cancer remains a major concern and cause of morbidity and mortality. Most of the modern anti-neoplastic therapies have severe side effects, and tumor cells often develop drug resistance. There is promise in the new generation of treatments (gene therapy, immunotherapy, vaccines, etc.) that are under development, but the efficacies and side effects of such therapies have so far been disappointing. Receptor-based therapies are not new, but many normal cells also present the same receptors reducing the specificity of such approaches. Several lytic peptides have been investigated because of they appear to kill cancer cells due to changes of their membrane potential. Thus, linking receptor-specific ligands to lytic peptides is expected to augment the specificity of targeting and decrease the toxicity of lytic peptides on normal cells. One such polypeptide is hecate (an analogue to the bee venom main component, melittin) that preferentially kills cancer cells at low doses. When this peptide is fused with the 81-95 amino acid fragment of chorionic gonadotropin-beta (CGbeta) subunit (hecate-CGbeta), it targets cells expressing luteinizing hormone receptor (LHR), even at very low doses, or when LHR is expressed at low level. Our recent data showed that this peptide conjugate is efficient in destroying LHR-positive cells in xenografts and more importantly in transgenic mouse models developing LHR-positive somatic cell tumors in gonads. The mechanism of action of hecate-CGbeta after binding to LHR is destruction of cell membranes resulting in rapid cell death by necrosis with minimal side effects. This review summarizes our findings on the action of this novel peptide and considers the future potential of this family of targeting peptides in the treatment of neoplasias.


Assuntos
Meliteno/análogos & derivados , Neoplasias Ovarianas/tratamento farmacológico , Receptores do LH/metabolismo , Neoplasias Testiculares/tratamento farmacológico , Animais , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico , Sistemas de Liberação de Medicamentos , Feminino , Terapia Genética , Humanos , Masculino , Meliteno/uso terapêutico , Modelos Biológicos , Neoplasias Ovarianas/metabolismo , Receptores do LH/antagonistas & inibidores , Receptores do LH/genética , Neoplasias Testiculares/metabolismo
10.
Mol Cell Endocrinol ; 269(1-2): 26-33, 2007 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-17382461

RESUMO

In a series of in vivo and in vitro experiments, it was shown that membrane disrupting lytic peptides (Hecate, Phor14, or Phor21) conjugated to a 15 amino acid segment of the beta chain of CG or to LHRH were able to target and destroy hormone dependent and independent human prostate cancer xenografts in nude mice. In vitro sensitivity of the cells to the drugs was directly related to LH/CG receptor expression, and pretreatment in vitro or in vivo with estrogens or FSH to enhance LH/CG receptor expression capacity and increased sensitivity to the drugs. Administration of unconjugated Hecate and LHRH was ineffective. Most importantly, all of the lytic peptide-betaCG conjugates tested were highly effective in destroying prostate cancer metastatic cells in lymph nodes, bones and lungs.


Assuntos
Carcinoma/tratamento farmacológico , Hormônio Liberador de Gonadotropina/uso terapêutico , Meliteno/análogos & derivados , Metástase Neoplásica/tratamento farmacológico , Neoplasias da Próstata/tratamento farmacológico , Animais , Carcinoma/patologia , Sobrevivência Celular/efeitos dos fármacos , Gonadotropina Coriônica Humana Subunidade beta/farmacologia , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico , Hormônio Liberador de Gonadotropina/química , Hormônio Liberador de Gonadotropina/farmacologia , Humanos , Masculino , Meliteno/farmacologia , Meliteno/uso terapêutico , Necrose/induzido quimicamente , Neoplasias da Próstata/patologia
11.
Mol Cell Endocrinol ; 260-262: 183-9, 2007 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-17101210

RESUMO

In a series of in vivo and in vitro experiments, the concept has been established that breast cancer cells that express LH/CG or LHRH receptors can be targeted and destroyed by constructs consisting of a lytic peptide moiety and a 15-amino acid segment of the beta-chain of CG or by an LHRH lytic peptide conjugate. Data obtained in vitro established the validity of this concept, showed the specificities of the Hecate-betaCG, and Phor14 and Phor21-betaCG conjugates in killing cells that express functional LH/CG receptors and proved that the LH/CG receptor capacity is directly related to the compound's specificity. In in vivo experiments, Hecate-betaCG, Phor14-betaCG, and Phor21-betaCG(ala) each caused highly significant reductions of tumor volume and tumor burden in nude mice bearing breast cancer xenografts; Hecate and Phor21 alone or conjugated with non-specific peptides were not effective. Most importantly, the lytic peptide conjugates were all highly effective in targeting and destroying disseminated breast cancer metastases in lymph nodes, bones, lungs and other organs.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico , Hormônio Liberador de Gonadotropina/uso terapêutico , Meliteno/análogos & derivados , Fragmentos de Peptídeos/uso terapêutico , Peptídeos/uso terapêutico , Sequência de Aminoácidos , Animais , Morte Celular , Gonadotropina Coriônica Humana Subunidade beta/química , Feminino , Luciferases/metabolismo , Pulmão/patologia , Linfonodos/patologia , Meliteno/química , Meliteno/uso terapêutico , Camundongos , Camundongos Nus , Dados de Sequência Molecular , Metástase Neoplásica , Transplante de Neoplasias , Fragmentos de Peptídeos/química , Peptídeos/química , Medula Espinal/patologia , Carga Tumoral
12.
Neoplasia ; 7(5): 497-508, 2005 May.
Artigo em Inglês | MEDLINE | ID: mdl-15967102

RESUMO

We investigated the antitumoral efficacy, endocrine consequences, and molecular mechanisms underlying cell death induced by the Hecate-chorionic gonadotropin (CG)beta conjugate, a fusion protein of a 23-amino acid lytic peptide Hecate with a 15-amino acid (81-95) fragment of the human CGbeta chain. Transgenic (TG) mice expressing the inhibin alpha-subunit promoter (inhalpha)/Simian Virus 40 T-antigen (Tag) transgene, developing luteinizing hormone (LH) receptor (R) expressing Leydig and granulosa cell tumors, and wild-type control littermates were treated either with vehicle, Hecate, or Hecate-CGbeta conjugate for 3 weeks. Hecate-CGbeta conjugate treatment reduced the testicular and ovarian tumor burden (P < .05), whereas a concomitant increase (testis; P < .05) or no change (ovary) in tumor volumes occured with Hectate treatment. A drop in serum progesterone, produced by the tumors, and an increase in LH levels occured in Hecate-CGbeta treated mice, in comparison with vehicle and Hecate groups, providing further support for the positive treatment response. Hecate-CGbeta conjugate induced a rapid and cell-specific membrane permeabilization of LHR-expressing cells in vitro, suggesting a necrotic mode of cell death without activation of apoptosis. These results prove the principle that the Hecate-CGbeta conjugate provides a novel specific lead into gonadal somatic cell cancer therapy by targeted destruction of LHR-expressing tumor cells.


Assuntos
Tumor de Células da Granulosa/terapia , Tumor de Células de Leydig/terapia , Meliteno/análogos & derivados , Receptores do LH/metabolismo , Clorometilcetonas de Aminoácidos/farmacologia , Animais , Apoptose , Northern Blotting , Caspase 3 , Caspases/metabolismo , Morte Celular , Linhagem Celular Tumoral , Separação Celular , Gonadotropina Coriônica Humana Subunidade beta/química , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico , Modelos Animais de Doenças , Ativação Enzimática , Feminino , Citometria de Fluxo , Humanos , Masculino , Meliteno/química , Meliteno/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Microscopia de Fluorescência , Necrose , Neoplasias Ovarianas/terapia , Progesterona/sangue , Regiões Promotoras Genéticas , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/metabolismo , Neoplasias Testiculares/terapia , Fatores de Tempo
13.
Hum Reprod ; 17(3): 659-65, 2002 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11870119

RESUMO

BACKGROUND: Enhanced vascularization appears to be important for follicular selection and maturation in both spontaneous and stimulated IVF cycles. Nitric oxide, formed in vivo from L-arginine, may play a key role in follicular maturation and ovulation. METHODS: To evaluate the role of L-arginine supplementation in controlled ovarian hyperstimulation, 37 IVF patients were divided into two groups according to ovarian stimulation protocols: group I, GnRH agonist plus pure (p)FSH plus oral L-arginine (n = 18); and group II, GnRH agonist plus pFSH plus placebo (n = 19). Hormonal, ultrasonographic and Doppler evaluations were performed, and plasma and follicular fluid nitrite/nitrate concentrations were monitored. RESULTS: Thirty-two patients completed the study. In group I (n = 16), plasma L-arginine concentrations increased from (basal) 87 +/- 12 micromol to 279 +/- 31 micromol (P = 0.002) on the day of beta-HCG administration. In this group, pFSH treatment was shorter (P = 0.039) than in group II (n = 16). The number of the follicles > or =17mm was lower (P = 0.038) in group I than group II. The "good quality" embryos were fewer in number (P = 0.034) and pregnancy rate, both per patient (P = 0.024) and per embryo transfer (P = 0.019), was lower in group I. In the L-arginine group, an increased follicular fluid concentration of nitrite/nitrate was observed. On day 8 of the cycle, elevated plasma estradiol levels were associated with decreased blood flow resistances of perifollicular arteries. Follicular fluid concentrations of nitrite/nitrate were inversely correlated with embryo quality (r = -0.613; P = 0.005) and perifollicular artery pulsatility index (r = -0.609; P = 0.021). CONCLUSIONS: L-Arginine supplementation may be detrimental to embryo quality and pregnancy rate during controlled ovarian hyperstimulation cycles.


Assuntos
Adjuvantes Farmacêuticos/uso terapêutico , Arginina/uso terapêutico , Indução da Ovulação , Adjuvantes Farmacêuticos/administração & dosagem , Adjuvantes Farmacêuticos/metabolismo , Administração Oral , Adulto , Arginina/administração & dosagem , Arginina/sangue , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Transferência Embrionária , Embrião de Mamíferos/fisiologia , Embrião de Mamíferos/ultraestrutura , Feminino , Fertilização in vitro , Hormônio Foliculoestimulante/uso terapêutico , Líquido Folicular/metabolismo , Hormônio Liberador de Gonadotropina/agonistas , Humanos , Nitratos/metabolismo , Nitritos/metabolismo , Folículo Ovariano/fisiopatologia , Gravidez , Taxa de Gravidez , Estudos Prospectivos , Valores de Referência
14.
Vet. Méx ; 32(4): 279-287, oct.-dic. 2001. tab, graf, CD-ROM
Artigo em Espanhol | LILACS | ID: lil-306654

RESUMO

La fertilidad en la vaca lechera ha disminuido significativamente en los últimos 40 años, esto último ha coincidido con un incremento en la producción de leche. Actualmente, el porcentaje de concepción (PC) en el primer servicio difícilmente supera 35 por ciento. La muerte embrionaria representa la principal causa de la falla en la concepción y es grave en las vacas repetidoras, en las cuales cerca de 50 por ciento de los embriones mueren durante los primeros 16 días después de la fertilización. La etiología de la muerte embrionaria es diversa; se ha señalado que las anormalidades en la función del cuerpo lúteo son causa importante; sin embargo, la información es contradictoria. En experiencias propias no se ha encontrado diferencia en la función lútea entre animales fértiles e infértiles ni entre animales gestantes y no gestantes; además, los resultados de estudios en los cuales suplementan con progesterona o inducen un cuerpo lúteo accesorio son variables. Aquí no se encontró ningún efecto del tratamiento con hCG los días seis o siete posinseminación. Los resultados de tratamientos con GnRH o hCG, al momento del servicio, también son variables; aunque los resultados globales indican que sí mejoran el PC, en experiencias propias no se ha encontrado un efecto positivo. El reconocimiento materno de la gestación es crítico para la sobrevivencia embrionaria; la presencia de folículos grandes durante los días 12-14 se asoció con baja fertilidad. Sin embargo, la eliminación de los folículos con GnRH o hCG ha aportado resultados contradictorios y globalmente no ha mostrado un efecto favorable. La administración de la hormona de crecimiento (bST) al momento de la inseminación, mejoró el PC en las vacas repetidoras y disminuyó los problemas degenerativos de los embriones en vacas repetidoras superovuladas.


Assuntos
Bovinos , Infertilidade , Indução da Ovulação/veterinária , Progesterona , Hormônio Liberador de Gonadotropina , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico
17.
Am J Obstet Gynecol ; 181(4): 853-7, 1999 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-10521741

RESUMO

OBJECTIVE: The purpose of this study was to test the capability of human chorionic gonadotropin to inhibit prostaglandin-induced preterm delivery in a murine model. STUDY DESIGN: A preterm delivery model was developed by using intraperitoneal injection of 20 microgram of prostaglandin F(2)(alpha) to induce preterm labor in C3H/HeN inbred mice. Mice were then pretreated with human chorionic gonadotropin 4 hours before administration of prostaglandin F(2)(alpha), and time to delivery of the first pup was recorded. After initial promising results, mice were then given increasing intraperitoneal doses of human chorionic gonadotropin (100 IU, 250 IU, or 1000 IU or sodium chloride solution vehicle) 4 hours after administration of prostaglandin F(2)(alpha). The specificity of the human chorionic gonadotropin effect was assessed by treating mice with whole human chorionic gonadotropin, an equal mass dose of the beta-subunit or the alpha-subunit of human chorionic gonadotropin, or an equal mass dose of luteinizing hormone 4 hours after administration of prostaglandin F(2)(alpha). Delivery times between groups were compared by using the Mann-Whitney U test and the log-rank test. Survival estimates were computed by using the Kaplan-Meier method. RESULTS: Pilot studies in 52 mice confirmed that a single intraperitoneal injection of 20 microgram of prostaglandin F(2)(alpha) on day 16 (80% gestation) consistently induced preterm delivery compared with the effect of sodium chloride solution on control mice (prostaglandin F(2)(alpha), 19.3 +/- 2.9 hours; sodium chloride solution, 53.5 +/- 13.6 hours; P <.0001). Mice pretreated with human chorionic gonadotropin (1000 IU) demonstrated significant delays in delivery times compared with the prostaglandin-only group (prostaglandin F(2)(alpha) only, 21.9 +/- 2. 0 hours; human chorionic gonadotropin pretreatment plus prostaglandin F(2)(alpha), 48.5 +/- 20 hours; P <.0001; n = 17). Mice treated with human chorionic gonadotropin (100 IU, 250 IU, 1000 IU) 4 hours after administration of prostaglandin F(2)(alpha) demonstrated significant dose-dependent inhibition of preterm delivery compared with the prostaglandin-only group (P <.00005; n = 34). Mice treated with the alpha-subunit or the beta-subunit of human chorionic gonadotropin after prostaglandin administration did not demonstrate delays in delivery times (P =.46; n = 27). Administration of luteinizing hormone delayed delivery compared with the effect of prostaglandin F(2)(alpha) on control animals (P <.05; n = 17); however, the effect was less pronounced than that seen with a mass equivalent of human chorionic gonadotropin. CONCLUSIONS: Human chorionic gonadotropin exhibits potent inhibition of prostaglandin-induced preterm delivery in mice. The effect is dose-dependent, and whole human chorionic gonadotropin is required to elicit inhibition. Further studies are needed to determine the safety and efficacy of human chorionic gonadotropin as a potential therapy for preterm labor inhibition in human pregnancy.


Assuntos
Gonadotropina Coriônica/uso terapêutico , Trabalho de Parto Prematuro/prevenção & controle , Animais , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico , Dinoprosta/administração & dosagem , Modelos Animais de Doenças , Feminino , Idade Gestacional , Subunidade alfa de Hormônios Glicoproteicos/uso terapêutico , Humanos , Injeções Intraperitoneais , Cinética , Hormônio Luteinizante/administração & dosagem , Camundongos , Camundongos Endogâmicos C3H , Trabalho de Parto Prematuro/induzido quimicamente , Gravidez
18.
Acta Med Port ; 12(1-3): 131-6, 1999.
Artigo em Português | MEDLINE | ID: mdl-10423887

RESUMO

This paper briefly reviews the literature on testicular descent and management implications for cryptorchidism. At present, we believe that descent of the testes in humans is a complex event mediated by both hormonal and mechanical factors. There is now good evidence that testicular descent occurs in two morphologic and hormonally distinct phases. Relative "transabdominal migration", which occurs in the 8th and 15th week of gestation, and "inguinoscrotal" migration, which occurs in the 28th and 35th week of gestation. The first phase is controlled by the Mullerian inhibiting factor (MIF), although this remains controversial. The second phase is androgen--dependent and mediated through the release nerve of the neuropeptide calcitonin gene-related peptide from the genitofemoral. Cryptorchidism can therefore result when any one or more of the involved factors malfunction. The therapeutic use of hCG has, however, been disappointing, and its role is confined to helping to distinguish the undescended testis. The demonstration of the pathological changes after one year of age has recently dictated much earlier surgical correction, but long-term follow-up is needed to prove the clinical benefit of this practice.


Assuntos
Criptorquidismo/diagnóstico , Criança , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico , Criptorquidismo/complicações , Criptorquidismo/embriologia , Criptorquidismo/etiologia , Criptorquidismo/patologia , Criptorquidismo/terapia , Humanos , Masculino , Testículo/embriologia , Testículo/patologia , Testículo/cirurgia
19.
Ginecol. & obstet ; 45(2): 112-5, abr. 1999. tab
Artigo em Espanhol | LILACS, LIPECS | ID: lil-270762

RESUMO

Objetivo: Determinar la correlación entre niveles de gonadotropina coriónica beta medidos en el segundo trimestre de la gestación y el riesgo de presentación de preeclampsia. Diseño: estudio prospectivo, descriptivo. Material: a 85 gestantes en un segundo trimestre se les determinó la sub unidad beta de la gonadotropina coriónica sérica, siendo seguidas hasta el término. Resultados: edad materna promedio 29,4 años, peso pregestacional promedio 55,7 kilos. Edad gestacional media a la toma de la muestra 20,6 semanas, 38 nulíparas y 47 multíparas. La concentración plasmática de la gonadotropina coriónica beta tuvo una media de 32,988 mUI/mL y un rango de 5000 - 14000 mUI/mL. Edad gestacional promedio al parto 38 semanas, 53 partos vaginales y 32 partos por cesárea. La preeclampsia se presentó en 14 de 85 gestantes (16 por ciento), 10 con preeclampsia leve y 4 con preeclampsia severa. La gonadotropina coriónica beta en la preeclampsia severa tuvo un rango de 60000 - 140000 mUI/mL y en la leve de 53000 - 71000 mUI/mL, diferencia altamente significativa. Conclusión: El valor de la gonadotropina coriónica beta en el segundo trimestre de la gestación, podría ser considerado un factor de riesgo para predecir la posible ocurrencia de la preeclampsia. Habría que realizar estudios más amplios para negar o confirmar estas hipótesis.


Assuntos
Humanos , Feminino , Adulto , Pré-Eclâmpsia/mortalidade , Pré-Eclâmpsia/terapia , Complicações na Gravidez , Fatores de Risco , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico , Estudos Prospectivos , Epidemiologia Descritiva
20.
Acta Otorhinolaryngol Belg ; 52(1): 29-36, 1998.
Artigo em Inglês | MEDLINE | ID: mdl-9581194

RESUMO

The epidemic form of Kaposi's sarcoma is associated with human immunodeficiency virus infection. Cutaneous and mucosal manifestations are frequently reported in the ENT sphere, mostly involving the oral cavity. The external and middle ear are only rarely concerned with only one case of a mastoid lesion without extension to the external auditory canal (EAC) being reported to this day. The present article describes the first case of involvement of the EAC with extension to adjacent structures. This patient presented other Kaposi lesions and had been treated by systemic hormonal therapy. Thereafter local injection of a cytotoxic agent was given without effect. Finally, radiotherapy resulted in a 50% regression of the tumour mass. The epidemiologic factors and therapeutic modalities with their results are described.


Assuntos
Meato Acústico Externo/patologia , Neoplasias da Orelha/diagnóstico , Sarcoma de Kaposi/diagnóstico , Adulto , Antineoplásicos Fitogênicos/uso terapêutico , Movimento Celular , Gonadotropina Coriônica Humana Subunidade beta/uso terapêutico , Meato Acústico Externo/efeitos da radiação , Neoplasias da Orelha/complicações , Neoplasias da Orelha/terapia , Gadolínio , Perda Auditiva Condutiva/diagnóstico , Perda Auditiva Condutiva/etiologia , Humanos , Imageamento por Ressonância Magnética , Masculino , Invasividade Neoplásica , Segunda Neoplasia Primária/patologia , Palato/patologia , Neoplasias Faríngeas/patologia , Radioisótopos , Sarcoma de Kaposi/complicações , Sarcoma de Kaposi/terapia , Tomografia Computadorizada por Raios X , Vimblastina/uso terapêutico
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