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1.
Anticancer Res ; 41(9): 4271-4276, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34475046

RESUMO

BACKGROUND/AIM: The anticancer mechanism of itraconazole remains unsolved; therefore, we studied itraconazole-induced alterations in specialized pro-resolving mediators (SPMs) in cancer cells. MATERIALS AND METHODS: The human cervical squamous carcinoma cell line CaSki was cultured with or without 1 µM itraconazole. Liquid chromatography/mass spectrometry analysis was conducted to identify SPMs that were influenced by itraconazole. Cell growth experiments were conducted using itraconazole and inhibitors targeting the metabolic pathways of candidate SPMs. RESULTS: Resolvin E3, resolvin E2, prostaglandin J2 (PGJ2), delta-12-PGJ2, and maresin 2 were identified as candidate SPMs. The 12/15-lipoxygenase inhibitor, which is involved in the conversion of 18-hydroxy-eicosapentaenoic acid to resolvin E3, attenuated the inhibitory effect of itraconazole. Inhibition of the PGJ2 metabolic pathway did not interfere with itraconazole treatment. CONCLUSION: The metabolic pathway of SPMs, including resolving E3, could be proposed as an anticancer target of itraconazole.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Ácidos Graxos Insaturados/metabolismo , Itraconazol/farmacologia , Inibidores de Lipoxigenase/farmacologia , Neoplasias do Colo do Útero/metabolismo , Carcinoma de Células Escamosas/tratamento farmacológico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Cromatografia Líquida , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Espectrometria de Massas , Redes e Vias Metabólicas/efeitos dos fármacos , Neoplasias do Colo do Útero/tratamento farmacológico
2.
Gynecol Oncol Rep ; 32: 100563, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32300630

RESUMO

A germline pathogenic variant in BRCA2 was secondarily found through genomic sequencing of uterine serous carcinoma. Clinical response to olaparib was observed in recurrent uterine serous carcinoma with a germline BRCA2 mutation. Here, we report, for the first time, a long-term clinical response to olaparib in a patient with uterine serous carcinoma and a germline pathogenic BRCA2 variant.

3.
J Obstet Gynaecol Res ; 45(1): 203-209, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30117238

RESUMO

AIM: To investigate the effects of leuprorelin using a self-administered quality-of-life (QOL) questionnaire in patients with recurrent gynecological cancer. METHODS: Records of patients who received 3.75 mg leuprorelin every 4 weeks for the treatment of recurrent gynecological cancer were retrospectively reviewed. The physical domain of the QOL questionnaire, Care Notebook, was used to assess physical symptoms. Symptom deterioration was defined as a ≥10-point increase in baseline score; otherwise, symptoms were defined as controlled. Radiological and serological responses were evaluated according to the 2011 Gynecological Cancer Intergroup criteria. RESULTS: From 2007 to 2015, 25 patients were administered leuprorelin for the treatment of epithelial ovarian cancer, granulosa cell tumor, endometrial cancer, endometrial stromal sarcoma and clear cell cervical cancer (in 13, 3, 6, 2 and 1 patients, respectively). Twenty patients had received a median of three lines (range 1-12 lines) of chemotherapy. Ten patients had progressive disease during their previous round of chemotherapy. Twenty patients completed the questionnaire every 4 weeks. Following leuprorelin treatment for 8 weeks, the symptom and disease control rates were 65% (13/20) and 44% (11/25), respectively. Two patients, one each with granulosa cell tumor and endometrial cancer, had stable disease at 6 months. Among the 20 patients who completed the QOL questionnaire, symptom control and disease control at 8 weeks showed a significant correlation (P = 0.016). CONCLUSION: Leuprorelin had minimal anticancer activity. The physical domain of the QOL questionnaire could be used to assess effects of hormonal treatment.


Assuntos
Antineoplásicos Hormonais/farmacologia , Neoplasias dos Genitais Femininos/tratamento farmacológico , Leuprolida/farmacologia , Recidiva Local de Neoplasia/tratamento farmacológico , Medidas de Resultados Relatados pelo Paciente , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/administração & dosagem , Feminino , Humanos , Leuprolida/administração & dosagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Inquéritos e Questionários
4.
BMC Cancer ; 18(1): 630, 2018 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-29866134

RESUMO

BACKGROUND: Primary malignant melanoma of the vagina is extremely rare, with a poorer prognosis than cutaneous malignant melanoma. Previous studies have explored the repurposing of itraconazole, a common oral anti-fungal agent, for the treatment of various cancers. Here, we describe a patient with metastatic, unresectable vaginal malignant melanoma treated with 200 mg oral itraconazole twice a day in a clinical window-of-opportunity trial. CASE PRESENTATION: A 64-year-old Japanese woman with vaginal and inguinal tumours was referred to our institution. On the basis of an initial diagnosis of vaginal cancer metastatic to the inguinal lymph nodes, we treated her with itraconazole in a clinical trial until the biopsy and imaging study results were obtained. During this period, biopsies were performed three times, and 18F-fluoro-deoxyglucose positron emission tomography (FDG/PET)-computed tomography (CT) was performed twice. Biopsy results confirmed the diagnosis of primary malignant melanoma of the vagina. Imaging studies revealed metastases to multiple sites, including the brain, for which she underwent gamma-knife radiosurgery. During the window period before nivolumab initiation, the patient received itraconazole for 30 days. Within a week of itraconazole initiation, pain in the inguinal nodes was ameliorated. PET-CT on days 6 and 30 showed a reduction in tumour size and FDG uptake, respectively. The biopsied specimens obtained on days 1, 13, and 30 were subjected to cDNA microarray analysis, which revealed a 100-fold downregulation in the transcription of four genes: STATH, EEF1A2, TTR, and CDH2. After 12 weeks of nivolumab administration, she developed progressive disease and grade 3 immune-related hepatitis. Discontinuation of nivolumab resulted in the occurrence of left pelvic and inguinal pain. Following re-challenge with itraconazole, the patient has not reported any pain for 4 months. CONCLUSION: The findings of this case suggest that itraconazole is a potential effective treatment option for primary malignant melanoma of the vagina. Moreover, we identified potential itraconazole target genes, which could help elucidate the mechanism underlying this disease and potentially aid in the development of new therapeutic agents.


Assuntos
Antineoplásicos/uso terapêutico , Itraconazol/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Vaginais/tratamento farmacológico , DNA Complementar/análise , Feminino , Humanos , Melanoma/diagnóstico por imagem , Melanoma/genética , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/genética , Análise Serial de Tecidos , Neoplasias Vaginais/diagnóstico por imagem , Neoplasias Vaginais/genética
5.
Gynecol Oncol Rep ; 24: 54-56, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29915800

RESUMO

Ovarian Sertoli cell tumors (SCTs) are rare sex cord tumors (Oliva et al., 2005). The standard treatment for high-grade SCTs is surgery followed by platinum-based chemotherapy. Although platinum-based chemotherapy is also an option for recurrent SCTs (Sigismondi et al., 2012), there is no established chemotherapy regimen for platinum-resistant recurrent SCTs. The effectiveness of pazopanib in treating epithelial ovarian cancer has recently been reported (du Bois et al., 2014; Pignata et al., 2015). In the case described herein, pazopanib was used to treat the platinum-resistant recurrence of a high-grade Sertoli cell tumor, and the response was evaluated by 18F-fluoro-deoxyglucose positron emission tomography (FDG-PET)-computed tomography (CT). Written informed consent to reporting the case was obtained from the patient.

6.
Gynecol Oncol Rep ; 24: 57-60, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29682600

RESUMO

Standard chemotherapy for women with advanced or recurrent cervical cancer involves a combination of paclitaxel, platinum, and bevacizumab. However, for patients who experience anaphylaxis in response to paclitaxel or platinum, have permanent peripheral neuropathy, or develop early recurrence or progressive disease during first-line chemotherapy, the development of a non-taxane non-platinum regimen is mandatory. Clinical trials using anti-angiogenic treatment demonstrated favorable outcomes in cases of highly vascularized cervical cancer. Metronomic chemotherapy has been considered an anti-angiogenic treatment, although its use in combination with bevacizumab has not been studied in cervical cancer. We treated four patients with recurrent cervical cancer with 50 mg of oral cyclophosphamide daily and 15 mg/kg of intravenous bevacizumab every 3 weeks (CFA-BEV). One patient experienced disease progression after 4 months, whereas the other three patients continued the regimen until their last follow-up at 13, 14, and 15 months, respectively. One patient suffered from grade 3 neutropenia; however, no grade 2 or higher non-hematological toxicities were observed. These cases demonstrate the use of CFA-BEV with minimal toxicity and expected anti-cancer activity and indicate that this regimen should be considered for second-line chemotherapy in advanced recurrent cervical cancer.

7.
J Cancer Res Ther ; 13(3): 446-450, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28862207

RESUMO

OBJECTIVES: We conducted a retrospective multi-institutional study to evaluate the efficacy and toxicity of intraperitoneal or intrapleural triamcinolone acetonide (TA), a slowly metabolized corticosteroid administration for the management of malignant ascites or pleural effusion. MATERIALS AND METHODS: The medical records of patients with gynecologic cancer who were treated with paracentesis or thoracocentesis followed by administration of 400 mg of TA between 2005 and 2014 were reviewed. RESULTS: The median age of the 74 eligible patients was 59 years. An Eastern Cooperative Oncology Group performance status 3-4 was present in 53 patients (73%), and 52 patients (70%) had ovarian cancer. Paracentesis followed by TA administration was performed in 65 patients (88%), and 37 patients (50%) were treated in a palliative setting. Chemotherapy or surgery after TA administration was performed in 37 patients (50%) in an aggressive setting, of which 14 patients (19%) were treated at the primary phase and 23 patients (31%) were treated at recurrent phase. The time interval of serial drainage was prolonged in 15 of 19 assessable patients, resulting in a response rate of 79% (95% confidence interval [95% CI]: 54-94%). Median overall survival after TA therapy in a palliative setting was 36 days (95% CI: 19-58 days). After TA therapy in a palliative setting, one patient complained of mild abdominal pain, two patients with advanced peritonitis carcinomatosis experienced bowel perforation, and three patients died within 7 days owing to disease progression. CONCLUSIONS: Intraperitoneal and intrapleural TA administration were feasible and effective in symptomatic control of ascites and pleural effusion.


Assuntos
Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Peritoneais/tratamento farmacológico , Triancinolona Acetonida/administração & dosagem , Adulto , Idoso , Ascite/complicações , Ascite/tratamento farmacológico , Ascite/patologia , Feminino , Neoplasias dos Genitais Femininos/complicações , Neoplasias dos Genitais Femininos/patologia , Humanos , Infusões Parenterais , Neoplasias Pulmonares/complicações , Neoplasias Pulmonares/patologia , Pessoa de Meia-Idade , Neoplasias Peritoneais/complicações , Neoplasias Peritoneais/patologia , Derrame Pleural Maligno/tratamento farmacológico , Derrame Pleural Maligno/patologia
8.
Oncol Lett ; 14(2): 1240-1246, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28789339

RESUMO

Itraconazole, a common anti-fungal agent, has demonstrated potential anticancer activity, including reversing chemoresistance mediated by P-glycoprotein, modulating the signal transduction pathways of Hedgehog, mechanistic target of rapamycin and Wnt/ß-catenin in cancer cells, inhibiting angiogenesis and lymphangiogenesis, and possibly interfering with cancer-stromal cell interactions. Clinical trials have suggested the clinical benefits of itraconazole monotherapy for prostate cancer and basal cell carcinoma, as well as the survival advantage of combination chemotherapy for relapsed non-small cell lung, ovarian, triple negative breast, pancreatic and biliary tract cancer. As drug repurposing is cost-effective and timesaving, a review was conducted of preclinical and clinical data focusing on the anticancer activity of itraconazole, and discusses the future directions for repurposing itraconazole as an anticancer agent.

9.
Anticancer Res ; 37(7): 3521-3526, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28668841

RESUMO

BACKGROUND/AIM: Repurposing itraconazole as an anticancer agent has been evaluated in several studies. The present study investigated whether itraconazole exerts an anticancer effect on cervical cancer cells. MATERIALS AND METHODS: CaSki and HeLa cells were cultured in itraconazole and vehicle after which colony-forming and cell viability assays were performed. Transcription and protein expression were assessed by cDNA microarray analysis and immunoblotting, respectively. RESULTS: Itraconazole suppressed proliferation of CaSki and HeLa cells in a dose- and time-dependent manner. Furthermore, CaSki cells were more significantly affected by itraconazole than HeLa cells. The microarray analysis showed an 8-fold down-regulation in the expression of GLI1, WNT4 and WNT10A among itraconazole-treated CaSki cells. Moreover, the transcription of sterol carrier protein-2 and ATP-binding cassette transporter-1 was unaffected by itraconazole. Immunoblots showed suppression in ß-catenin expression and Akt phosphorylation. CONCLUSION: Itraconazole is a multi-targeting anticancer agent and a promising therapeutic agent for cervical cancer.


Assuntos
Proliferação de Células/efeitos dos fármacos , Proteínas Hedgehog/metabolismo , Itraconazol/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Neoplasias do Colo do Útero/tratamento farmacológico , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos/farmacologia , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Regulação para Baixo/efeitos dos fármacos , Feminino , Células HeLa , Humanos , Transdução de Sinais/efeitos dos fármacos , Neoplasias do Colo do Útero/metabolismo , Proteína Wnt4/metabolismo , Proteína GLI1 em Dedos de Zinco/metabolismo
10.
Anticancer Res ; 37(2): 515-519, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28179296

RESUMO

BACKGROUND: Itraconazole is a common antifungal agent that has demonstrated anticancer activity in preclinical and clinical studies. This study investigated whether itraconazole exerts this effect in endometrial cancer (EC) cells. MATERIALS AND METHODS: Cell viability was evaluated with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and gene and protein expression were assessed by microarray analysis and immunoblotting, respectively, in five EC cell lines. RESULTS: Itraconazole-suppressed proliferation of AN3-CA, HEC-1A and Ishikawa cells (p<0.05) but not of HEC-50B or SNG-II cells. Itraconazole did not suppress GLI1 or GLI2 transcription but did inhibit the expression of mammalian target of rapamycin (mTOR) signaling components in AN3-CA and HEC-1A cells, while inducing that of microtubule-associated protein 1A/1B-light chain 3-II, a marker of autophagy. ATP-binding cassette transporter A1 gene was down-regulated in Ishikawa, HEC-50B and SNG-II cells. CONCLUSION: Itraconazole treatment suppresses the growth of EC cells by inhibiting AKT/mTOR signalling.


Assuntos
Neoplasias do Endométrio/tratamento farmacológico , Itraconazol/farmacologia , Proteína Oncogênica v-akt/antagonistas & inibidores , Serina-Treonina Quinases TOR/antagonistas & inibidores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Proteína Oncogênica v-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
11.
Asia Pac J Oncol Nurs ; 3(3): 272-280, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27981171

RESUMO

OBJECTIVE: This study was to examine the effect of complementary therapy (CT) for nurses with high stress levels. It was taken before we employ this technique for cancer survivors because cancer patients are a heterogeneous group that requires substantial resources to investigate. METHODS: A quasi-experimental design with five groups was employed for this study. The groups were examined whether there were effects for reducing the stress and the differences in effectiveness among four intervention groups and a nonintervention group. Stress relief was measured using pulse rate and blood pressure measurements and the short form of the profile of mood states (POMS-SF). The participants practiced the therapy for 20 min twice per week for 3 weeks. A two-way factorial analysis of variance was used to analyze the data. RESULTS: The study enrolled 98 nurses (92 female and 6 male) with a mean age of 37.3 ± 10.5 years (range: 22-60 years). Fifty-nine nurses had 10 or more years of nursing experience. There were significant differences in pulse rate and the POMS-SF scores. All groups were effective for reducing the stress level of high-stress nurses, whereas four intervention CT groups were not more effective than nonintervention group. CONCLUSIONS: The complementary therapies were useful for nurses with high stress levels. Thus, they can be used as a self-management tool for such nurses. Afterward, we will use the CT for cancer survivors to determine whether it can improve the quality of life of cancer patients.

12.
Gynecol Oncol Rep ; 17: 60-4, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27617285

RESUMO

A 48-year-old woman underwent a total abdominal hysterectomy after preoperative diagnosis of multiple uterine leiomyomas. The histopathological diagnosis was leiomyosarcoma (LMS). After 47 months, multiple lung metastases were detected and resected. The patient was also diagnosed with pelvic bone metastasis and received six cycles of adjuvant chemotherapy with gemcitabine plus docetaxel and local radiation therapy to control the pain. Seventy-seven months from the initial diagnosis, she had a headache and developed left hemiparesis and aphasia. Imaging studies detected a solitary brain metastasis in the right frontal lobe. The patient underwent a craniotomy and resection of the lesion, which was a confirmed metastasis from uterine LMS by histopathology. One month after the craniotomy, the patient experienced lower abdominal pain, and a pelvic metastasis was detected. She was prescribed oral pazopanib (800 mg per day). For twelve months, she remained asymptomatic, but gradually, pelvic pain increased due to pelvic mass growth. After 14 months of pazopanib treatment, pazopanib was discontinued. To date, for 18 months after the brain surgery, she is alive with disease, and the brain metastasis has not recurred.

13.
Anticancer Res ; 36(1): 149-53, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26722038

RESUMO

BACKGROUND: There exist limited therapeutic opportunities for the treatment of endometrial cancer (EC). Itraconazole, a common anti-fungal agent and a potent inhibitor of the Hedgehog pathway, has been shown to be clinically effective for various types of cancers, but its clinical efficacy for EC is unknown. Herein, we evaluated the efficacy of itraconazole in treating EC. MATERIALS AND METHODS: We performed immunohistochemistry on EC tumour samples including serous endometrial intraepithelial carcinoma (SEIC). We further evaluated the in vitro efficacy of itraconazole for inhibiting proliferation and migration of EC cell lines. RESULTS: Sonic Hedgehog and glioma-associated oncogene homolog 1 (GLI1) were expressed in SEIC and endometrioid adenocarcinoma. We found that itraconazole significantly inhibited tumour cell growth in both dose-dependent and time-dependent manners and inhibited migration of HEC-1A cells. CONCLUSION: Hedgehog signaling plays a role in carcinogenesis and malignant progression in EC. Itraconazole at a physiological dose may suppress progression of EC.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Endometrioide/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Endométrio/tratamento farmacológico , Itraconazol/farmacologia , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Carcinoma Endometrioide/metabolismo , Carcinoma Endometrioide/patologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Neoplasias do Endométrio/metabolismo , Neoplasias do Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Fatores de Tempo , Proteína GLI1 em Dedos de Zinco
14.
Anticancer Res ; 36(1): 199-203, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26722044

RESUMO

BACKGROUND: There exist limited therapeutic opportunities regarding the treatment of endometrial cancer (EC), and novel therapies based on the molecular profiling of EC cells are required. MATERIALS AND METHODS: We used microarray analysis of EC tumour samples in order to identify tumour-specific changes regarding gene expression. RESULTS: It was found that gremlin 2, an inhibitor of bone morphogenetic protein (BMP) signaling, was repressed in EC samples, and that gremlin 2 inhibited tumour cell growth. CONCLUSION: Down-regulation of gremlin 2 may lead to carcinogenesis and progression of EC. We suggest that re-activation of gremlin 2-associated pathways could suppress EC progression and should thus be explored as a potential novel therapeutic approach.


Assuntos
Neoplasias do Endométrio/imunologia , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Movimento Celular , Proliferação de Células , Neoplasias do Endométrio/patologia , Feminino , Humanos , Técnicas In Vitro , Transdução de Sinais
15.
Cortex ; 75: 1-19, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26707082

RESUMO

Lesion-deficit studies support the hypothesis that the left anterior temporal lobe (ATL) plays a critical role in retrieving names of concrete entities. They further suggest that different regions of the left ATL process different conceptual categories. Here we test the specificity of these relationships and whether the anatomical segregation is related to the underlying organization of white matter connections. We reanalyzed data from a previous lesion study of naming and recognition across five categories of concrete entities. In voxelwise logistic regressions of lesion-deficit associations, we formally incorporated measures of disconnection of long-range association fiber tracts (FTs) and covaried for recognition and non-category-specific naming deficits. We also performed fiber tractwise analyses to assess whether damage to specific FTs was preferentially associated with category-selective naming deficits. Damage to the basolateral ATL was associated with naming deficits for both unique (famous faces) and non-unique entities, whereas the damage to the temporal pole was associated with naming deficits for unique entities only. This segregation pattern remained after accounting for comorbid recognition deficits or naming deficits in other categories. The tractwise analyses showed that damage to the uncinate fasciculus (UNC) was associated with naming impairments for unique entities, while damage to the inferior longitudinal fasciculus (ILF) was associated with naming impairments for non-unique entities. Covarying for FT transection in voxelwise analyses rendered the cortical association for unique entities more focal. These results are consistent with the partial segregation of brain system support for name retrieval of unique and non-unique entities at both the level of cortical components and underlying white matter fiber bundles. Our study reconciles theoretic accounts of the functional organization of the left ATL by revealing both category-related processing and semantic hub sectors.


Assuntos
Mapeamento Encefálico , Nomes , Reconhecimento Psicológico/fisiologia , Lobo Temporal/fisiologia , Adulto , Mapeamento Encefálico/métodos , Face/patologia , Humanos , Memória/fisiologia , Testes Neuropsicológicos , Semântica
16.
Anticancer Res ; 35(9): 4923-7, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26254389

RESUMO

AIM: We evaluated the efficacy and safety of itraconazole after first-line chemotherapy in patients with metastatic biliary tract cancer (BTC). PATIENTS AND METHODS: We retrospectively reviewed data from patients with histologically-diagnosed BTC with distant metastases who had received one or more lines of chemotherapy and subsequent itraconazole chemotherapy. RESULTS: Among 28 enrolled patients, 26 (93%) received docetaxel (35 mg/m(2)), gemcitabine (1,000 mg/m(2)), and carboplatin (AUC4) on day 1 and oral itraconazole solution (400 mg) on days -2 to 2, repeated every 2 weeks. Two patients received docetaxel plus itraconazole with irinotecan. Two complete responses and 14 partial responses were observed, with a response rate of 57%. The median overall survival was 12.0 months. During 160 cycles, 21 (75%) and 17 (61%) patients had grade 3/4 neutropenia and thrombocytopenia, respectively. Two patients (7%) experienced febrile neutropenia. CONCLUSION: Combination chemotherapy with itraconazole after first-line chemotherapy is promising for patients with metastatic BTC.


Assuntos
Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/patologia , Itraconazol/uso terapêutico , Adulto , Idoso , Antineoplásicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Itraconazol/efeitos adversos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Resultado do Tratamento
17.
Anticancer Res ; 35(7): 4191-6, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26124377

RESUMO

BACKGROUND: We evaluated chemotherapy with itraconazole (a common anti-fungal agent that is a potent inhibitor of the Hedgehog pathway, P-glycoprotein, and angiogenesis) for treating progressive pancreatic cancer. PATIENTS AND METHODS: We retrospectively reviewed the medical charts of patients with histologically-diagnosed pancreatic cancer who had received first- or second-line chemotherapy and subsequent chemotherapy with itraconazole. RESULTS: A total of 38 patients received docetaxel (35 mg/m(2)), gemcitabine (1,000 mg/m(2)), and carboplatin (area under the curve, 4 mg/min/ml) on day 1 and oral itraconazole solution (400 mg) on days -2 to 2, repeated every 2 weeks. One complete response and 13 partial responses were observed, for a response rate of 37%. Eight (21%) patients experienced febrile neutropenia. The median overall survival was 11.4 months (95% confidence interval=8.5-21.2 months). CONCLUSION: Combination chemotherapy with itraconazole is promising for prolonging overall survival, with acceptable toxicities in the second-line setting of pancreatic cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carboplatina/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel , Feminino , Humanos , Itraconazol/administração & dosagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxoides/administração & dosagem
18.
Gynecol Oncol Rep ; 11: 1-3, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26076082

RESUMO

•Endometrial stromal sarcoma disseminated after morcellation•Complete remission of pelvic recurrence was achieved by oophorectomy.•Laparoscopic confirmation of remission of recurrent disease.

19.
J Obstet Gynaecol Res ; 41(1): 162-6, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25163509

RESUMO

Several cases of the uterus being preserved after diagnosis of endometrial stromal sarcoma (ESS) have been reported. Most of these patients were alive and did not experience relapse, but this might have reflected the short follow-up period, given the indolent recurrence of ESS. We report the first fatal case of ESS 10 years after fertility-sparing management. A specimen obtained from the last operation showed loss of estrogen receptor status and expression of c-kit without c-kit or PDGFR-α gene mutations.


Assuntos
Neoplasias do Endométrio/terapia , Tratamentos com Preservação do Órgão , Sarcoma do Estroma Endometrial/terapia , Adulto , Evolução Fatal , Feminino , Humanos
20.
Neuroimage Clin ; 6: 388-97, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25379452

RESUMO

Elucidating the brain basis for psychological processes and behavior is a fundamental aim of cognitive neuroscience. The lesion method, using voxel-based statistical analysis, is an important approach to this goal, identifying neural structures that are necessary for the support of specific mental operations, and complementing the strengths of functional imaging techniques. Lesion coverage in a population is by nature spatially heterogeneous and biased, systematically affecting the ability of lesion-deficit correlation methods to detect and localize functional associations. We have developed a simulator that allows investigators to model parameters in a lesion-deficit study and characterize the statistical bias in lesion deficit detection coverage that will result from specific assumptions. We used the simulator to assess the signal detection properties and localization accuracy of standard lesion-deficit correlation methods, under a simple truth model - that a critical region of interest (CR), when damaged, gives rise to a deficit. We considered voxel-based lesion-symptom mapping (VLSM) and proportional MAP-3 (PM3). Using regression analysis, we examined if the pattern of outcome statistics can be explained by simulation parameters, factors that are inherent to anatomic parcels, and lesion coverage of the population, which consisted of a representative sample of 351 subjects drawn from the Iowa Patient Registry. We examined the effect of using nonparametric versus parametric statistics to obtain thresholded maps and the effect of correcting for multiple comparisons using false discovery rate or cluster-based correction. Our results, which are derived from samples of realistic lesions, indicate that even a simple truth model yields localization errors that are systematic and pervasive, averaging 2 cm in the standard anatomic space, and tending to be directed towards areas of greater anatomic coverage. This displacement positions the center of mass of the detected region in a different anatomical region 87% of the time. This basic result is not affected by the choice of PM3 vs VLSM as the fundamental approach, nor is localization error ameliorated by incorporation of lesion size as a covariate in the VLSM approach, or by data distribution-driven approaches to controlling multiple spatial comparisons (false discovery rate or cluster-based correction approaches). Our simulations offer a quantitative basis for interpreting lesion studies in cognitive neuroscience. We suggest ways in which lesion simulation and analysis frameworks could be productively extended.


Assuntos
Lesões Encefálicas/diagnóstico , Lesões Encefálicas/psicologia , Encéfalo/patologia , Diagnóstico por Computador , Simulação por Computador , Interpretação Estatística de Dados , Humanos
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