RESUMO
Oral squamous cell carcinoma (OSCC) is one of the most common malignant tumors with a low quality of life. Because traditional surgical treatment often causes large wounds and then affects the quality of life of patients, it is urgent to find new and efficient drugs with good safety for clinical treatment. This study aimed to identify potential anticancer drugs starting from the traditional Chinese medicine Salvia miltiorrhiza extract. Cryptotanshinone, a compound isolated from the Chinese herb Salvia miltiorrhiza, was found to significantly induce apoptosis and inhibit proliferation in OSCC. By electron microscopy, autophagosomes were found. Confocal fluorescence microscopy data showed that cryptotanshinone significantly induced autophagy in OSCC cells. Mechanistically, the western blot assay indicated that cryptotanshinone induced cell autophagy through the activation of the LC3 pathway, whereas the autophagy inhibitor 3-methyladenine attenuated these effects. Furthermore, we demonstrated that cryptotanshinone had a significant antitumor effect in a tumor xenograft model, and no damage to vital organs was observed. Our findings provide evidence that cryptotanshinone may be a novel therapeutic strategy for the treatment of OSCC.
Assuntos
Antineoplásicos , Carcinoma de Células Pequenas , Medicamentos de Ervas Chinesas , Neoplasias Bucais , Humanos , Masculino , Adulto , Fenantrenos/uso terapêutico , Neoplasias Bucais/tratamento farmacológico , Autofagia , Antineoplásicos/farmacologia , Carcinoma de Células Pequenas/tratamento farmacológico , Qualidade de VidaRESUMO
Subglottic small cell carcinoma (SSMCC) is a rare type of neoplasm, meaning that laryngeal cancer guidelines in several countries, including the National Comprehensive Cancer Network (NCCN) guidelines, do not include treatment principles for SSMCC. Angiogenesis is an established factor in tumor initiation, growth, and dissemination. Apatinib mesylate, an orally administered drug, is a novel inhibitor of vascular endothelial growth factor receptor-2, a key mediator of angiogenesis, and has been shown to be safe and efficacious in the treatment of certain types of malignant tumors. To the best of our knowledge, there are few reports on the treatment of SSMCC with apatinib combined with concurrent chemoradiotherapy. In the present report of SSMCC in a 64-year-old woman, oral apatinib was given daily at a dose of 250 mg in combination with concurrent chemoradiotherapy; the only toxicities reported were mild leukopenia and finger numbness. Clear and rapid efficacy was observed with the disappearance of the tumor mass. Our findings indicate that apatinib combined with concurrent chemoradiotherapy may be effective in patients with SSMCC, with adverse reactions within the manageable range, thus representing an additional treatment option for this type of malignancy.
Assuntos
Carcinoma de Células Pequenas , Neoplasias Pulmonares , Carcinoma de Células Pequenas/tratamento farmacológico , Quimiorradioterapia , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Pessoa de Meia-Idade , Piridinas , Fator A de Crescimento do Endotélio VascularRESUMO
Purpose: The ganglioside fucosyl-GM1 (FucGM1) is a tumor-associated antigen expressed in a large percentage of human small cell lung cancer (SCLC) tumors, but absent in most normal adult tissues, making it a promising target in immuno-oncology. This study was undertaken to evaluate the preclinical efficacy of BMS-986012, a novel, nonfucosylated, fully human IgG1 antibody that binds specifically to FucGM1.Experimental Design: The antitumor activity of BMS-986012 was evaluated in in vitro assays using SCLC cells and in mouse xenograft and syngeneic tumor models, with and without chemotherapeutic agents and checkpoint inhibitors.Results: BMS-986012 showed a high binding affinity for FcγRIIIa (CD16), which resulted in enhanced antibody-dependent cellular cytotoxicity (ADCC) against FucGM1-expressing tumor cell lines. BMS-986012-mediated tumor cell killing was also observed in complement-dependent cytotoxicity (CDC) and antibody-dependent cellular phagocytosis (ADCP) assays. In several mouse SCLC models, BMS-986012 demonstrated efficacy and was well tolerated. In the DMS79 xenograft model, tumor regression was achieved with BMS-986012 doses of 0.3 mg/kg and greater; antitumor activity was enhanced when BMS-986012 was combined with standard-of-care cisplatin or etoposide. In a syngeneic model, tumors derived from a genetically engineered model of SCLC were treated with BMS-986012 or anti-FucGM1 with a mouse IgG2a Fc and their responses evaluated; when BMS-986012 was combined with anti-PD-1 or anti-CD137 antibody, therapeutic responses significantly improved.Conclusions: Single-agent BMS-986012 demonstrated robust antitumor activity, with the addition of chemotherapeutic or immunomodulatory agents further inhibiting SCLC growth in the same models. These preclinical data supported evaluation of BMS-986012 in a phase I clinical trial of patients with relapsed, refractory SCLC. Clin Cancer Res; 24(20); 5178-89. ©2018 AACR.
Assuntos
Antineoplásicos Imunológicos/farmacologia , Gangliosídeo G(M1)/análogos & derivados , Animais , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Antígenos de Neoplasias/imunologia , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/metabolismo , Carcinoma de Células Pequenas/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Gangliosídeo G(M1)/antagonistas & inibidores , Gangliosídeo G(M1)/imunologia , Gangliosídeo G(M1)/metabolismo , Humanos , Imuno-Histoquímica , Imunomodulação/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , Ligação Proteica , Receptores de IgG/metabolismo , Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral/antagonistas & inibidores , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: We previously reported that 22% of lung cancer patients experienced a Grade 2 or 3 elevation in creatinine after chemotherapy containing cisplatin. We conducted a Phase II trial to evaluate the safety and efficacy of short hydration. METHODS: The major eligibility criteria included patients with lung cancer for whom a ≥75 mg/m(2) cisplatin-based regimen was indicated and adequate organ function. Cisplatin was administered with pre- and post-hydration containing 10 mEq of potassium chloride in 500 ml of fluid over a 60-min period. Immediately before the administration of cisplatin, mannitol (20%, 200 ml) was administered as forced diuresis over 30 min. And magnesium sulfate (8 mEq) was added to pre-hydration. RESULTS: Forty-four patients were enrolled between April and December 2011. The patients included 29 men and 15 women with a median (range) age of 64 (42-74) years. Twenty patients received cisplatin and pemetrexed as their most frequent regimen and 38 patients received three to four cycles of chemotherapy. The median (range) duration and volume of the chemotherapies were 4.0 (3.3-6.8) h and 1600 (1550-2050) ml, respectively. Of the 44 patients, 43 (97.8%) completed the cisplatin-based chemotherapy without Grade 2 or higher renal dysfunction. The only patient who had Grade 2 elevation in creatinine (maximum value 1.7 mg/dl) had prompt improvement in creatinine levels and completed four cycles of chemotherapy. CONCLUSIONS: The short hydration is safe without severe renal toxicities in regimens containing cisplatin (≥75 mg/m(2)) for patients with lung cancer.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Hidratação/métodos , Neoplasias Pulmonares/tratamento farmacológico , Magnésio/administração & dosagem , Insuficiência Renal/prevenção & controle , Adenocarcinoma/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores/sangue , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Creatinina/sangue , Feminino , Trato Gastrointestinal/efeitos dos fármacos , Glutamatos/administração & dosagem , Glutamatos/efeitos adversos , Guanina/administração & dosagem , Guanina/efeitos adversos , Guanina/análogos & derivados , Humanos , Japão , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/fisiopatologia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Pemetrexede , Estudos Prospectivos , Radioterapia Adjuvante , Insuficiência Renal/induzido quimicamente , Resultado do TratamentoRESUMO
PURPOSE: Ovarian small cell carcinoma of the hypercalcaemic type is a very rare and highly aggressive malignant disease, mainly affecting young women. Due to the rarity of this tumour entity, prospective randomised trials are unlikely to be conducted, and the only retrospective analysis based on a large case series is from 1994. Since diagnostic and treatment modalities may have changed, we initiated this analysis. METHODS: The aim of our study was to review and analyse cases published since 1975 to validate former findings and to gather more information about therapy options, diagnostic and prognostic factors. A systematic literature search of the PubMed/Medline database was performed assessing all articles until September 2010. All retrieved articles were evaluated and cross-checked for references on the topic. In total, 135 cases were included, selected from 62 case reports and smaller case studies. RESULTS: Small cell carcinoma mostly affects women with a mean age of 23.4 years. They present with unspecific symptoms like abdominal pain or palpable mass, sometimes accompanied by an elevated calcium or CA-125 serum concentration. The tumour appears nearly almost unilaterally, mostly affecting the right ovary. Tumour stage is a clearly prognostic factor. Adjuvant chemotherapy consisting of etoposide, cisplatinum/carboplatinum or vinca alkaloids has shown improved survival, whereas radiotherapy has not. CONCLUSIONS: In spite of limitations this analysis provides new insights especially with respect to therapeutic aspects. This review underlines the importance of case reports in rare tumour entities in order to answer open questions.
Assuntos
Carcinoma de Células Pequenas/diagnóstico , Neoplasias Ovarianas/diagnóstico , Adolescente , Adulto , Idoso , Antineoplásicos/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/radioterapia , Carcinoma de Células Pequenas/cirurgia , Criança , Pré-Escolar , Terapia Combinada , Feminino , Humanos , Lactente , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/radioterapia , Neoplasias Ovarianas/cirurgia , Fotoquimioterapia , Prognóstico , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: Sorafenib has demonstrated single agent activity in non-small cell (NSCLC) and small cell lung cancer (SCLC). Carboplatin/pemetrexed (CbP) and cisplatin/etoposide (PE) are commonly used in the treatment of these diseases. METHODS: A phase I trial escalating doses of sorafenib in combination with fixed doses of PE (Arm A) or CbP (Arm B) was performed using a 3-patient cohort design to determine the maximum tolerated dose (MTD) and dose-limiting toxicities (DLT); DLT were assessed in the first cycle. The trial was subsequently amended with closure of Arm B and to include Arm C with a reduced dose of carboplatin. RESULTS: Between 9/2007 and 9/2008, 20 pts were treated on the trial; median age 62 (range 42-73), male/female ratio 12/8, PS 0/1 ratio 6/14, and median number of prior therapies 2 (range 1-4). The most common tumor types were NSCLC and SCLC. On Arm A at dose level 0 (sorafenib 200 mg BID), 2 of 4 patients experienced DLT; 2 patients were enrolled at dose level -1 (sorafenib 200 mg QD) without DLT, but this arm was closed due to slow accrual. On Arm B, 2 of 3 patients experienced DLT at dose level 0 (sorafenib 200 mg BID). On Arm C at dose level 0 (sorafenib 200 mg BID), 1 of 6 patients experienced DLT, and at dose level +1 (sorafenib 400 mg BID) 2 of 5 patients experienced a DLT. CONCLUSIONS: The MTD of sorafenib was 200 mg BID continuously in combination with carboplatin (AUC of 5) and pemetrexed 500 mg/m² every 3 weeks. However, only 6 patients were treated at this dose level, and the results should be interpreted cautiously.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzenossulfonatos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Piridinas/uso terapêutico , Adulto , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/toxicidade , Benzenossulfonatos/administração & dosagem , Carboplatina/administração & dosagem , Carboplatina/uso terapêutico , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Etoposídeo/administração & dosagem , Etoposídeo/uso terapêutico , Feminino , Glutamatos/administração & dosagem , Glutamatos/uso terapêutico , Guanina/administração & dosagem , Guanina/análogos & derivados , Guanina/uso terapêutico , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Niacinamida/análogos & derivados , Pemetrexede , Compostos de Fenilureia , Piridinas/administração & dosagem , Sorafenibe , Resultado do TratamentoRESUMO
PURPOSE: Desmoplastic round small cell tumor (DRSCT) is a rare intraabdominal mesenchymal tissue neoplasm in young patients and spreads through the abdominal cavity. Its prognosis is poor despite a multimodal therapy including chemotherapy, radiotherapy, and surgical cytoreduction (CS). hyperthermic intraperitoneal chemotherapy (HIPEC) is considered as an additional strategy in the treatment of peritoneal carcinomatosis; for this reason, we planned to treat selected cases of children with DRSCT using CS and HIPEC. METHODS: Peritoneal disease extension was evaluated according to Gilly classification. Surgical cytoreduction was considered as completeness of cytoreduction-0 when no macroscopic nodule was residual; HIPEC was performed according to the open technique. RESULTS: We described 3 cases: the 2 first cases were realized for palliative conditions and the last one was operated on with curative intent. There was no postoperative mortality. One patient was reoperated for a gallbladder perforation. There was no other complication related to HIPEC procedure. CONCLUSIONS: Surgical cytoreduction and HIPEC provide a local alternative approach to systemic chemotherapy in the control of microscopic peritoneal disease in DRSCT, with an acceptable morbidity, and may be considered as a potential beneficial adjuvant waiting for a more specific targeted therapy against the fusion protein.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma/tratamento farmacológico , Carcinoma/cirurgia , Quimioterapia do Câncer por Perfusão Regional/métodos , Hipertermia Induzida/métodos , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/patologia , Adenocarcinoma/cirurgia , Adolescente , Carcinoma/patologia , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/cirurgia , Terapia Combinada , Intervalo Livre de Doença , Feminino , Humanos , Injeções Intraperitoneais , Masculino , Cuidados Paliativos , Neoplasias Peritoneais/patologia , Neoplasias Peritoneais/secundário , Peritônio/patologia , Peritônio/cirurgia , Resultado do Tratamento , Carga Tumoral/efeitos dos fármacosRESUMO
BACKGROUND AND PURPOSE: Extrapulmonary small cell carcinoma (EPSCC) is a rare disease, which has a slightly better prognosis than small cell lung cancer, but still dismal. Gynecologic small cell malignancies tend to show a better survival than similar histologies of other regions. However, of five reported cases of vulvar manifestation only one patient was disease-free at the time of publication with limited follow-up. CASE REPORT: The authors describe a case of locally advanced small cell vulva carcinoma infiltrating the anal sphincter and urethra with spread to inguinal lymph nodes treated by radiochemotherapy and regional hyperthermia. After three cycles of carboplatin/ etoposide, computed tomography and magnetic resonance imaging indicated only little regressive transformations but overall stable disease. Surgical options were excluded. Therefore, curative radiotherapy to a total dose of > 65 Gy to macroscopic tumor, chemotherapy with cisplatin weekly, and regional hyperthermia were performed. Acute severe toxicity was limited to skin reactions. Despite the disadvantageous situation with inguinal lymph node metastases and chemoresistance, the multimodal therapy yielded a 5-year disease-free survival. CONCLUSION: Thus, the trimodal regimen of radiochemotherapy plus regional hyperthermia offered a curative chance in spite of resistance to the standard chemotherapy for irresectable, locally advanced small cell carcinoma of the vulva. Therefore, this approach merits further evaluation for limited disease of EPSCC.
Assuntos
Carcinoma de Células Pequenas/radioterapia , Neoplasias Vulvares/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carboplatina/administração & dosagem , Carcinoma de Células Pequenas/diagnóstico por imagem , Carcinoma de Células Pequenas/tratamento farmacológico , Terapia Combinada/métodos , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Humanos , Hipertermia Induzida , Imageamento por Ressonância Magnética , Radiografia , Tomografia Computadorizada de Emissão , Neoplasias Vulvares/tratamento farmacológicoRESUMO
Although the advancement of the chemotherapy of non-small cell lung cancer and small cell lung cancer is remarkable in recent years, it is still unsatisfactory. Therefore, some new agents or a new treatment strategy for lung cancer is required. Amrubicin is a totally synthetic anthracycline anticancer drug that acts as a potent topoisomerase II inhibitor. Recently, amrubicin has been approved in Japan for the treatment of small- and non-small cell lung cancers and some clinical trials about amrubicin were conducted in Japan, and promising results have been reported for the treatment of small cell lung cancer in particular. The preclinical, pharmacology and clinical data of amrubicin for the treatment of advanced lung cancer are reviewed.
Assuntos
Antraciclinas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Animais , Antraciclinas/efeitos adversos , Antraciclinas/farmacologia , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/patologia , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/patologia , Ensaios Clínicos como Assunto , Aprovação de Drogas , Avaliação Pré-Clínica de Medicamentos , Humanos , Japão , Neoplasias Pulmonares/patologia , Inibidores da Topoisomerase IIRESUMO
PURPOSE: To determine the efficacy and toxicity of extended-field radiotherapy (RT) with concurrent platinum-based chemotherapy in patients with uterine cervical carcinoma and positive para-aortic nodes. METHODS AND MATERIALS: We retrospectively reviewed the results for 33 women with Stage IB-IVB cervical cancer. Each patient had received 59.4 Gy, including a three-dimensional conformal boost to the para-aortic lymph nodes and 41.4-50.4 Gy of external beam radiotherapy to the pelvis. Each patient also underwent six or seven applications of high-dose-rate brachytherapy (median, 5 Gy to point A at each session). RESULTS: The median follow-up period of surviving patients was 39 months. The most common acute toxicity was hematologic, observed in 23 women. Severe acute and late gastrointestinal toxicity was observed in 3 and 4 patients, respectively. More than three-quarters of patients showed a complete response, encompassing the primary mass, metastatic pelvic, and para-aortic lymph nodes. Of the 33 women, 15 had no evidence of disease, 6 had persistent disease, 4 developed in-field failures, and 6 developed distant failures. The 5-year overall and disease-free survival rate was 47% and 42%, respectively. CONCLUSION: Concurrent chemoradiotherapy with extended-field radiotherapy is feasible in women with uterine cervical carcinoma and positive para-aortic lymph nodes, with acceptable late morbidity and a high survival rate, although it was accompanied by substantial acute toxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo do Útero/tratamento farmacológico , Neoplasias do Colo do Útero/radioterapia , Adenocarcinoma de Células Claras/tratamento farmacológico , Adenocarcinoma de Células Claras/patologia , Adenocarcinoma de Células Claras/radioterapia , Adulto , Idoso , Aorta , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/radioterapia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/radioterapia , Cisplatino/administração & dosagem , Terapia Combinada/métodos , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Radioisótopos de Irídio/uso terapêutico , Metástase Linfática/radioterapia , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Radioterapia/efeitos adversos , Radioterapia/métodos , Dosagem Radioterapêutica , Indução de Remissão , Estudos Retrospectivos , Resultado do Tratamento , Neoplasias do Colo do Útero/mortalidade , Neoplasias do Colo do Útero/patologiaAssuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Oncologia , Neoplasias/diagnóstico , Neoplasias/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais , Neoplasias Encefálicas/terapia , Neoplasias da Mama/tratamento farmacológico , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/tratamento farmacológico , Quimioterapia Adjuvante , Neoplasias Colorretais/tratamento farmacológico , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Neoplasias Pulmonares/tratamento farmacológico , Programas de Rastreamento , Neoplasias/prevenção & controle , Compostos Organoplatínicos/administração & dosagem , Sociedades MédicasRESUMO
Angiogenesis is mediated mainly by vascular endothelial growth factor (VEGF), and VEGF causes rapid growth in cancers, including human small-cell lung cancer (SCLC). The anti-angiogenic strategy of treating cancer using VEGF receptor (VEGFR) inhibition is currently of great interest. We tested the effects of the VEGFR2 tyrosine kinase inhibitor (TKI) vandetanib on the proliferation of two kinds of SCLC cell lines: SBC-1 cells, with detectable VEGFR2 expression and MS-1-L cells, without detectable VEGFR2 expression. To evaluate the anti-tumor and anti-angiogenic effects of vandetanib in vivo, we grafted SBC-1 and MS-1-L cells into mice. After a 3-week treatment, we measured the tumor size and histologically evaluated necrosis and apoptosis using H&E and TUNEL staining, respectively. The microvessels in the xenografts were also quantified by immunostaining of CD31. Vandetanib did not affect the proliferation of SBC-1 cells, but stimulated the growth of MS-1-L cells. In the SCLC xenograft model, vandetanib inhibited growth and tumor angiogenesis in a dose-dependent manner in SBC-1 xenografts. Vandetanib inhibited the growth of MS-1-L xenografts at a low dose (<12.5 mg/kg/day), but it did not affect tumor size or change microvessel counts at a higher dose. Interestingly, secretion of VEGF increased significantly in the MS-1-L cell line in the presence of a high dose of vandetanib in vitro. The effects of vandetanib on tumor angiogenesis were different in SBC-1 and MS-1-L cell lines. Production of angiogenic factors such as VEGF by the tumor potentially stimulates tumor angiogenesis and results in the acquisition of resistance to VEGFR TKI.
Assuntos
Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Piperidinas/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Quinazolinas/administração & dosagem , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Carcinoma de Células Pequenas/irrigação sanguínea , Carcinoma de Células Pequenas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Marcação In Situ das Extremidades Cortadas , Neoplasias Pulmonares/irrigação sanguínea , Neoplasias Pulmonares/metabolismo , Camundongos , Necrose , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator A de Crescimento do Endotélio Vascular/biossíntese , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 2 de Fatores de Crescimento do Endotélio Vascular/efeitos dos fármacos , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Using tigogenin as starting material, (20S)-20-hydroxycholestane-3,6-dione (1), (16S, 20S)-16,20-dihydroxycholestan-3-one (2), (20S)-20-hydroxycholest-1-ene-3,16-dione (3) and (20S)-20-hydroxycholest-4-ene-3,16-dione (4), natural polyoxygenated steroids from the gorgonian, Leptogorgia sarmentosa, were synthesized in four steps. Antitumor activity against three tumor cell lines (breast cancer, MCF7, lung cancer NCI and oral cancer KB) was evaluated. Two compounds (3 and 4) showed strong activity against NCI (IC(50) 6.16 and 10.51 microM) and moderate activity against MCF7 and KB, the IC(50) being in the range 30.65-47.22 microM. Compound 2 showed moderate activity against NCI (IC(50) 42.68 microM) but was inactive against MCF7 and KB whereas compound 1 showed no activity against all tested cells.
Assuntos
Colestanos/síntese química , Colestanos/toxicidade , Cnidários/química , Citotoxinas/química , Esteroides/síntese química , Esteroides/toxicidade , Adenocarcinoma/tratamento farmacológico , Animais , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Linhagem Celular Tumoral , Colestanos/química , Citotoxinas/isolamento & purificação , Avaliação Pré-Clínica de Medicamentos , Humanos , Concentração Inibidora 50 , Neoplasias Pulmonares/tratamento farmacológico , Estrutura Molecular , Neoplasias Bucais/tratamento farmacológico , Esteroides/química , Esteroides/isolamento & purificaçãoRESUMO
Platinum drugs are major chemotherapeutic agents that are used alone or in combination with other systemic agents and/or radiation therapy in the management of many human malignancies. All three platinum drugs approved by the Food and Drug Administration, cisplatin, carboplatin, and oxaliplatin, are administrated intravenously. Satraplatin is the first orally administered platinum drug under active clinical investigation. Satraplatin and its major metabolite, JM118, have shown antineoplastic activity in in vitro, in vivo, and in clinical settings. Use of satraplatin as an alternative platinum cytotoxic agent is particularly attractive because of the convenience of administration, milder toxicity profile, lack of cross-resistance with cisplatin, theoretical advantage as a radiosensitizer, and activity in cancers historically nonresponsive to platinum drugs. The most mature clinical data for satraplatin come from the recently completed phase III trial that investigated the efficacy of satraplatin and prednisone on hormone-refractory prostate cancer patients who had failed a course of other chemotherapy agents. Preliminary reports show that the combination is statistically superior to placebo and prednisone in multiple end points, including progression-free survival, prostate-specific antigen response, objective tumor response, pain response, and duration of pain response. The difference in overall survival, however, did not reach statistical significance.
Assuntos
Neoplasias/tratamento farmacológico , Compostos Organoplatínicos/uso terapêutico , Administração Oral , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/tratamento farmacológico , Ensaios Clínicos como Assunto , Avaliação Pré-Clínica de Medicamentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Modelos Biológicos , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/farmacocinética , Compostos de Platina/administração & dosagem , Compostos de Platina/uso terapêutico , Neoplasias da Próstata/tratamento farmacológicoRESUMO
BACKGROUND: Recently, there have been extensive efforts to evaluate the chemopreventive role of substances present in natural products. The aim of this study was to examine the effects of the main groups of compounds (salicylalcohol derivates, flavonoids, proanthocyanidins), and salicin isolated from willow bark extract BNO 1455 on proliferation and apoptosis in human colon and cancer cells. METHODS: We used human colon cyclooxygenase-2 (COX-2)-positive HT 29 and (COX-2)-negative HCT 116 or lung COX-2 proficient A 549 and low COX-2 expressing SW2 cells. After treatment for 72 h with various concentrations of single substances and acetylsalicylic acid (ASA) as control, inhibition of cell growth and cytotoxicity were measured by colorimetric WST-1 assay and propidium iodide uptake by flow cytometry, respectively. Apoptotic cells were identified by annexin V adhesion using flow cytometry. RESULTS: Studies on dose-dependent effects of BNO 1455 and its fractions showed anti-proliferative activity of all compounds with 50% maximal growth inhibitory concentrations (GI(50)) between 33.3 and 103.3 microg/ml for flavonoids and proanthocyanidins fractions and 50.0-243.0 microg/ml for salicylalcohol derivates and extract. Apoptosis induction was confirmed by annexin V adherence and analysis of cell morphology based on light scattering characteristics using flow cytometry in all cell lines at GI(50). CONCLUSIONS: We showed that willow bark extract BNO 1455 an its fractions inhibit the cell growth and promote apoptosis in human colon and lung cancer cell lines irrespective of their COX-selectivity.
Assuntos
Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/patologia , Neoplasias Pulmonares/patologia , Casca de Planta/química , Extratos Vegetais/farmacologia , Salix , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/patologia , Sobrevivência Celular/efeitos dos fármacos , Neoplasias do Colo/tratamento farmacológico , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Flavonoides/química , Citometria de Fluxo , Células HT29/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Proteínas de Membrana/metabolismo , Proantocianidinas/química , Salicilatos/química , Células Tumorais Cultivadas/efeitos dos fármacosRESUMO
Gastric small cell carcinomas are rather rare. The incidence of small cell carcinomas of all histological types of gastric tumors is about 0.1%. Small cell carcinoma is a very aggressive cancer with a poor prognosis,and there is no effective chemotherapy to date. We experienced a case of small cell carcinoma of the stomach with relatively long survival from combination chemotherapy. A 75-year-old man underwent total gastrectomy, and liver metastasis was recognized 5 months postoperatively. We used combination chemotherapy with tegafur/gimeracil/oteracil potassium+cisplatin and irinotecan hydrochloride+cisplatin, and he has obtained a long survival time. We should gather more chemotherapy cases and establish some effective regimens for small cell carcinoma of the stomach.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Gástricas/tratamento farmacológico , Adenocarcinoma/cirurgia , Idoso , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Carcinoma de Células Pequenas/cirurgia , Quimioterapia Adjuvante , Cisplatino/administração & dosagem , Vias de Administração de Medicamentos , Combinação de Medicamentos , Gastrectomia , Humanos , Irinotecano , Excisão de Linfonodo , Masculino , Ácido Oxônico/administração & dosagem , Neoplasias Gástricas/cirurgia , Sobreviventes , Tegafur/administração & dosagemRESUMO
A 64-year-old man with a small-cell bronchus carcinoma and metastases was treated with chemotherapy and developed conjunctivitis and necrosis of the eyelids caused by Pseudomonas aeruginosa.
Assuntos
Anti-Infecciosos/uso terapêutico , Ciprofloxacina/uso terapêutico , Conjuntivite Bacteriana/diagnóstico , Pálpebras/patologia , Infecções por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/patogenicidade , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos Antineoplásicos , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/patologia , Conjuntivite Bacteriana/etiologia , Humanos , Hospedeiro Imunocomprometido , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Necrose , Infecções por Pseudomonas/etiologia , Resultado do TratamentoRESUMO
BACKGROUND: Small-cell neuroendocrine carcinoma has been recognized as a rare histologic variant occurring in only 0.5% to 2% of prostatic primary tumors. However, recent autopsy studies suggest development to this phenotype in up to 10% to 20% of the cases with hormone-refractory disease. CASE PRESENTATION: A case of conventional adenocarcinoma before androgen-ablation therapy but showing progression to small-cell neuroendocrine carcinoma at the recurrence. The immunohistochemistry of the tumor showed strong positive staining for progastrin-releasing peptide (ProGRP), a carboxy terminal region common to 3 precursors for gastrin-releasing peptide, but almost negative staining for chromogranin-A and prostate-specific antigen. Combination chemotherapy based on cisplatin and etoposide was effective for controlling the tumor progression for 7 months, and the serum ProGRP level correlated well to the clinical course. Neither objective nor subjective responses were observed to somatostatin analogue therapy performed in the late stage of disease. CONCLUSIONS: The present case reminds the urologist that small-cell neuroendocrine carcinoma may be a variant form of disease recurrence during androgen ablation in advanced prostate cancer. A strategic approach for this phenotype evaluating serum neuroendocrine markers, such as ProGRP, should be taken when serum prostate-specific antigen does not reflect the disease state. This approach would allow one to choose alternative therapies targeting neuroendocrine cells other than androgen ablation.
Assuntos
Carcinoma de Células Pequenas/patologia , Recidiva Local de Neoplasia/patologia , Neoplasias da Próstata/patologia , Idoso , Carcinoma de Células Pequenas/sangue , Carcinoma de Células Pequenas/tratamento farmacológico , Cromogranina A , Cromograninas/sangue , Humanos , Imuno-Histoquímica , Masculino , Peptídeos/sangue , Fosfopiruvato Hidratase/sangue , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/sangue , Neoplasias da Próstata/tratamento farmacológico , Precursores de Proteínas/sangueRESUMO
AIM: A randomized, open label with blind assessment, controlled trial was performed to assess efficacy and adverse-event profile of vitamin E, given as supplementation for prophylaxis against cisplatin-induced peripheral neuropathy (CIPN). PATIENTS AND METHODS: A total of 30 patients scheduled to receive six courses of cumulative cisplatin-based regimens were randomly allocated to treatment and control groups and were then studied by means of neurological examination and electrophysiological study. Patients assigned to group I (n=14) orally received vitamin E at a daily dose of 600 mg/day during chemotherapy and 3 months after its cessation were compared to patients of group II (n=16), who received no vitamin E supplementation and served as controls. The severity of neurotoxicity was summarized by means of a modified Peripheral Neuropathy (PNP) score. RESULTS: The incidence of neurotoxicity differed significantly between groups, occurring in 3/14 (21.4%) of patients assigned to the vitamin E supplementation group and in 11/16 (68.5%) of controls (p=0.026). The relative risk (RR) of developing neurotoxicity was significantly higher in case of controls, RR=2.51, 95% C.I.=1.16-5.47. Mean PNP scores were 4.99+/-1.33 for patients of group I and 10.47+/-10.62 for controls, (p=0.023). None of the adverse events or deaths occurred, were judged as likely to be related to the vitamin E supplementation. CONCLUSION: Vitamin E effectively and safely protects patients with cancer from occurrence of cisplatin neurotoxicity.
Assuntos
Antineoplásicos/efeitos adversos , Antioxidantes/uso terapêutico , Cisplatino/efeitos adversos , Suplementos Nutricionais , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Doenças do Sistema Nervoso Periférico/prevenção & controle , Vitamina E/uso terapêutico , Potenciais de Ação/efeitos dos fármacos , Adulto , Idoso , Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Antioxidantes/efeitos adversos , Carcinoma de Células Pequenas/tratamento farmacológico , Cisplatino/administração & dosagem , Método Duplo-Cego , Feminino , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Humanos , Incidência , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso Periférico/fisiopatologia , Nervo Fibular/efeitos dos fármacos , Nervo Fibular/fisiopatologia , Desempenho Psicomotor/efeitos dos fármacos , Projetos de Pesquisa , Índice de Gravidade de Doença , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Testiculares/tratamento farmacológico , Resultado do Tratamento , Nervo Ulnar/efeitos dos fármacos , Nervo Ulnar/fisiopatologia , Neoplasias do Colo do Útero/tratamento farmacológico , Vitamina E/efeitos adversosRESUMO
Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive malignancy with distinctive histological features: a nesting pattern of cellular growth within dense desmoplastic stroma, occurring in young population with male predominance. The mean survival period is only about 1.5-2.5 years. The tumor has co-expressed epithelial, muscle, and neural markers in immunohistochemical studies. This work reports a 27-year-old man presenting with hematemesis and chronic constipation. Serial studies including endoscopy, upper gastrointestinal series, abdominal computed tomography and barium enema study showed disseminated involvement of visceral organs. The patient underwent aggressive surgery and received postoperative adjuvant chemotherapy consisting of 5-fluorouracil, cyclophosphamide, etoposide, doxorubicin, and cisplatin. He survived without any disease for 20 mo after the surgery. No standard treatment protocol has been established. Aggressive surgery combined with postoperative multi-agent adjuvant chemotherapy is justified not only to relieve symptoms but also to try to improve the outcome in this advanced DSRCT young patient.