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1.
Anticancer Res ; 39(10): 5565-5572, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570451

RESUMO

BACKGROUND/AIM: The aim of the study was to evaluate the status of extravasated platelet activation (EPA) surrounding podoplanin (PDPN)-positive cancer-associated fibroblasts (CAFs) in pancreatic cancer stroma by neoadjuvant chemotherapy. PATIENTS AND METHODS: A total of 74 patients were enrolled in this study. We investigated CD42b and PDPN expression in the groups of untreated, gemcitabine (GEM) alone, GEM plus S-1 (GS) and GEM plus nab-paclitaxel (GnP). RESULTS: CD42b expression in surrounding CAFs was observed in 58% patients. CD42b expression was significantly correlated with PDPN expression. CD42b-positive cases were significantly lower in the group treated with GnP than in the untreated group and groups treated with GEM alone or GS. PDPN expression was reduced in the GnP group, as revealed by markedly disorganized collagen and a low density of PDPN-positive fibroblasts. There was a significantly lower CD42b expression and fewer PDPN-positive fibroblasts in the GnP group than in untreated, GEM alone, and GS groups, but there was no significant difference between the latter three groups. CONCLUSION: There is a significant association between EPA and PDPN-positive CAFs in pancreatic cancer stroma. Our data suggest that the GnP regimen decreases EPA through PDPN-positive CAF depletion.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fibroblastos Associados a Câncer/efeitos dos fármacos , Glicoproteínas de Membrana/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Ativação Plaquetária/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Albuminas/uso terapêutico , Fibroblastos Associados a Câncer/metabolismo , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Combinação de Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Ácido Oxônico/uso terapêutico , Paclitaxel/uso terapêutico , Neoplasias Pancreáticas/metabolismo , Complexo Glicoproteico GPIb-IX de Plaquetas/metabolismo , Tegafur/uso terapêutico
2.
Anticancer Res ; 39(10): 5645-5652, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570462

RESUMO

BACKGROUND/AIM: The aim of our study was to assess the predictive role of primary tumour sidedness (PTS) in patients with metastatic colorectal cancer (mCRC) harbouring wild-type RAS and treated with targeted agents. PATIENTS AND METHODS: The cohort included 178 patients treated with first-line chemotherapy plus cetuximab, panitumumab or bevacizumab. RESULTS: We observed longer progression-free survival (PFS) and overall survival (OS) in patients with left-sided (L-CRC) compared to right-sided tumours (R-CRC) treated with anti-EGFR mAbs (p=0.0033 and p=0.0037), while there was no difference in patients treated with bevacizumab (p=0.076 and p=0.56). Finally, we observed longer PFS and OS in patients with L-CRC treated with anti-EGFR mAbs and those with R-CRC treated with bevacizumab compared to the reverse combination (p=0.0002 and p=0.011). CONCLUSION: PTS is a predictive factor for anti-EGFR mAbs, not for bevacizumab. Superior survival was observed when anti-EGFR mAbs were used for L-CRC and bevacizumab for R-CRC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/patologia , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Idoso , Anticorpos Monoclonais/administração & dosagem , Bevacizumab/administração & dosagem , Cetuximab/administração & dosagem , Neoplasias Colorretais/genética , Intervalo Livre de Doença , Receptores ErbB/genética , Feminino , Genes ras/genética , Humanos , Masculino , Panitumumabe/administração & dosagem
3.
Anticancer Res ; 39(10): 5741-5745, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31570476

RESUMO

BACKGROUND/AIM: Cardiovascular risk factors (CVRFs) predict cardiotoxicity in cancer patients but their role in late cardiac toxicity is less clear. PATIENTS AND METHODS: This was a retrospective analysis of patients treated with anthracyclines (A) and/or trastuzumab (T) and a correlation with early (≤5 years) or late (>5 years) cardiac toxicity, and baseline CVRFs and CVRFs at toxicity time. RESULTS: A total of 610 patients were included, 422 with (Group A) and 188 without (Group B) baseline CVRFs. In group A toxicity incidence was 4.7% with all events during treatment or immediately after [mean onset time 0.7 years (range=0.2-1.6)]. Events rate was 3.2% in group B with all events after five years [mean time onset 6.9 years (range=5.2-7.5)]. All group B patients who developed late cardiac toxicity presented with CVRFs at the time of toxicity not reported before. CONCLUSION: CVRFs could predict late cardiac toxicity and their control should be part of the survivorship program.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Cardiotoxicidade/etiologia , Cardiopatias/induzido quimicamente , Adulto , Idoso , Antraciclinas/administração & dosagem , Antraciclinas/efeitos adversos , Antineoplásicos Imunológicos/efeitos adversos , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trastuzumab/administração & dosagem , Trastuzumab/efeitos adversos
4.
Gan To Kagaku Ryoho ; 46(8): 1259-1263, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31501367

RESUMO

We retrospectively analyzed adverse effects(AEs), overall survival(OS), and progression-free survival(PFS)in 15 consecutive patients treated with FOLFIRINOX as the first-line treatment for recurrent or unresectable pancreatic ductal adenocarcinoma( PDAC)between February 2014 and December 2017 in our hospital. Eleven patients were treated for unresectable PDAC with distant metastases(UR-M), and 4 were treated for locally advanced unresectable PDAC(UR-LA). The median age was 56(range: 40-75)years. Nine patients were male, and 6 were female. The performance status was 0 or 1 in all patients. Tumors were located in the pancreas head in 8 cases and in the body-tail in 7 cases. Grade 5 AEs were observed in 1 case in which liver abscess causing sepsis resulted in mortality. The response rate was 20.0%, and the disease control rate was 66.7%. Two patients underwent conversion surgery after FOLFIRINOX treatment. Seven patients received a nab-paclitaxel plus gemcitabine regimen as second-line treatment. The median OS and PFS were 17.0 and 8.4 months, respectively, and the 1-year survival rate was 66.7%. FOLFIRINOX for recurrent and unresectable PDAC showed relatively good tumor control. However, strict attention is required for severe AEs. Conversion surgery might be effective in patients who are good responders even if they have metastatic disease.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Pancreáticas , Adulto , Idoso , Carcinoma Ductal Pancreático , Feminino , Fluoruracila , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/tratamento farmacológico , Estudos Retrospectivos
5.
Gan To Kagaku Ryoho ; 46(8): 1299-1302, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31501374

RESUMO

A 74-year-old man was referred to our hospital because of a gastric tumor. A Borrmann type 2 gastric tumor was found on upper gastrointestinal endoscopy, but tissue biopsy indicated only necrotic tissue and the preoperative diagnosis was difficult. Contrast CT and FDG-PET revealed lymphadenopathy at multiple sites accompanied by high accumulation of FDG in the perigastric lymph nodes, left upper collarbicular fossa, bilateral hilar ganglia, and longitudinal cauda. Because the tumor was strongly suspected to be gastric cancer or malignant lymphoma, distal gastrectomy was performed. The tumor was finally diagnosed as a poorly differentiated adenocarcinoma with multiple lymph node metastasis. S-1 plus cisplatin therapy was administered as first-line chemotherapy, and paclitaxel(PTX)plus ramucirumab(RAM)therapy was administered as secondline chemotherapy. PTX plus RAM therapy was effective, and the patient achieved complete remission(CR), as observed on imaging. However, because adverse events such as numbness in the periphery of the limbs were noted, PTX plus RAM therapy was discontinued per the patient's request. Currently, 13 months since the interruption of treatment, the CR has been maintained, as determined on imaging.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas , Idoso , Anticorpos Monoclonais , Gastrectomia , Humanos , Masculino , Paclitaxel , Neoplasias Gástricas/tratamento farmacológico
6.
Gan To Kagaku Ryoho ; 46(8): 1303-1306, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31501375

RESUMO

A 75-year-old woman presented with difficulty in swallowing. Esophagogastroduodenoscopy(EGD)revealed a Borrmann type 3 advanced gastric cardia carcinoma. Computed tomography(CT)revealed three lymph node metastases, and thus, the preoperative diagnosis was cT4aN2M0, cStage ⅢB. However, the patient refused resection, and chemotherapy was initiated. The chemotherapy regimen was sequentially changed based on the macroscopic characteristics of the lesion: S-1 plus CDDP followed by S-1 alone, S-1 plus PTX, and PTX alone. We have continued to follow-upthe lesion using EGD and CT, and have observed the macroscopic characteristics of the advanced gastric carcinoma treated without resection for 7 years.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas , Idoso , Cisplatino , Feminino , Seguimentos , Gastrectomia , Humanos , Ácido Oxônico , Neoplasias Gástricas/tratamento farmacológico , Tegafur
7.
Gan To Kagaku Ryoho ; 46(8): 1323-1325, 2019 Aug.
Artigo em Japonês | MEDLINE | ID: mdl-31501380

RESUMO

A 63-year-old woman was admitted to our hospital owing to advanced rectal carcinoma. The patient underwent laparoscopic lowanterior resectionwith D3 lymph node dissection and partial resection of the uterus. The histopathological diagnosis was fT4bN2M0, fStage Ⅲb. Thus, capecitabine plus oxaliplatin(CapeOX)therapy as adjuvant chemotherapy was scheduled for 6 months. However, after the 4th course of chemotherapy, contrast-enhanced CT revealed multiple metastases of the rectal carcinoma including metastases in the liver, peritoneum, retroperitoneum, and subcutaneous tissue of the left lower back. The patient received palliative treatment and died 8 months after surgery. Only a fewcases of subcutaneous metastasis of rectal carcinoma have been reported. Therefore, we herein report this case with a review of the literature.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Retais , Capecitabina , Quimioterapia Adjuvante , Feminino , Humanos , Pessoa de Meia-Idade , Oxaliplatina , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/cirurgia , Tela Subcutânea
8.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(9): 890-893, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31506148

RESUMO

OBJECTIVE: To study the long-term clinical effect of the CCLG-ALL2008 regimen in the treatment of children newly diagnosed with acute lymphoblastic leukemia (ALL) with different molecular biological features. METHODS: A total of 940 children who were newly diagnosed with ALL were enrolled in this study. The children were treated with the CCLG-ALL2008 regimen. A retrospective analysis was performed for the long-term outcome of ALL children with different molecular biological features. RESULTS: Among the 940 children with ALL, there were 570 boys and 370 girls, with a median age of onset of 5 years (range 1-15 years) and a median follow-up time of 65 months (range 3-123 months). The complete response (CR) rate was 96.7%, the predicted 10-year overall survival (OS) rate was 76.5%±1.5%, and the event-free survival (EFS) rate was 62.6%±3.0%. After CR was achieved after treatment, the overall recurrence rate was 21.9%. The children with positive ETV6-RUNX1 had the lowest recurrence rate and were prone to late recurrence, and those with positive MLL rearrangement had the highest recurrence rate and were prone to early recurrence. The children with positive ETV6-RUNX1 had a significantly higher predicted 10-year OS rate than those with positive TCF3-PBX1, BCR-ABL, or MLL rearrangement and those without molecular biological features (P<0.05). The children with positive ETV6-RUNX1 had a significantly higher predicted 10-year EFS rate than those with positive BCR-ABL or MLL rearrangement (P<0.05). CONCLUSIONS: Molecular biological features may affect the long-term prognosis of children with ALL, and positive MLL rearrangement and BCR-ABL fusion gene are indicators of poor prognosis. Children with positive ETV6-RUNX1 fusion gene have the highest long-term survival rate.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adolescente , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Proteínas de Fusão bcr-abl , Humanos , Lactente , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Prognóstico , Estudos Retrospectivos
9.
Zhonghua Xue Ye Xue Za Zhi ; 40(8): 625-632, 2019 Aug 14.
Artigo em Chinês | MEDLINE | ID: mdl-31495127

RESUMO

Objective: To compare the difference of efficacy between traditional Hyper-CVAD/MA regimen and the adolescents inspired chemotherapy regimen, CH ALL-01, in treatment of adult Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph(+) ALL) . Methods: In this study we retrospectively analyzed 158 Ph(+) ALL patients receiving Hyper-CVAD/MA regimen (n=63) or CHALL-01 regimen (n=95) in our center and Changzheng hospital from January 2007 to December 2017, excluding patients with chronic myeloid leukemia in blast crisis. Tyrosine kinase inhibitor (TKI) was administered during induction and consolidation chemotherapy. Patients who underwent hematopoietic stem cell transplantation received TKI as maintenance therapy. Results: Of them, 91.1% (144/158) patients achieved complete remission (CR) after 1-2 courses of induction. CR rate was 90.5% (57/63) for patients in Hyper-CVAD/MA group and 91.6% (87/95) for patients in CHALL-01 group. There was no difference in CR rates between the two groups (χ(2)=0.057, P=0.811) . The last follow-up was June 2018. A cohort of 134 CR patients could be used for further analysis, among them, 53 patients received Hyper-CVAD/MA regimen and other 81 patients received CHALL-01 regimen. The molecular remission rates were significantly higher in CHALL-01 group (complete molecular response: 44.4%vs 22.6%; major molecular response: 9.9% vs 18.9%) (χ(2)=7.216, P=0.027) . For the patients in Hyper-CVAD/MA group, the 4-year overall survival (OS) was 44.81% (95%CI: 30.80%-57.86%) and the 4-year disease free survival (DFS) was 37.95% (95%CI: 24.87%-50.93%) . For patients received CHALL-01 regimen, the 4-year OS was 55.63% (95%CI: 39.07%-69.36%) (P=0.037) and 4 year DFS was 49.06% (95%CI: 34.24%-62.29%) (P=0.015) , while there was no significant difference in 4 year cumulative incidence of relapse (CIR) (P=0.328) or cumulative incidence of nonrelapse mortality (CI-NRM) (P=0.138) . The rate of pulmonary infection was lower in patients received CHALL-01 regimen compared with patients received Hyper-CVAD regimen (43.4% vs 67.9%, χ(2)=7.908, P=0.005) . Conclusions: Outcome with CHALL-01 regimen appeared better than that with the Hyper-CVAD/MA regimen in Ph(+) ALL, which has lower incidence of pulmonary infection, higher molecular remission rate and better OS and DFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cromossomo Filadélfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Adulto , Ciclofosfamida , Dexametasona , Doxorrubicina , Humanos , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Estudos Retrospectivos , Vincristina
10.
Zhonghua Xue Ye Xue Za Zhi ; 40(8): 633-638, 2019 Aug 14.
Artigo em Chinês | MEDLINE | ID: mdl-31495128

RESUMO

Objective: To analyze the therapeutic effect of a modified LMB89 Group C regimen in the treatment of pediatric high-risk Burkitt lymphoma. Methods: The clinical data of 172 children with newly diagnosed high-risk Burkitt lymphoma from January 2007 to April 2017 were retrospectively analyzed. All the cases were treated with the modified LMB89 Group C regimen. Results: The median age of the patients was 6 (1-14) years. The sex ratio was 5.1∶1, 144 boys (83.7%) and 28 girls (16.3%) . According to St. Jude staging classification, 2 patients (1.2%) were in stage Ⅱ, 54 (31.4%) in stage Ⅲ and 116 (67.4%) in stage Ⅳ. Of them, 46 patients (26.7%) had mature B cell acute lymphoblastic leukemia (B-ALL) , and 52 patients had central nervous system (CNS) involvement. According to risk group, the patients can be divided into group C1 (CNS1, without testicles/ovaries involvement, n=65) , group C2 (CNS2, testicles/ovaries involvement, n=55) and group C3 (CNS3, n=52) . A total of 145 patients received rituximab combined with chemotherapy during the treatment, 10 patients suffered from progressive disease and died, and 5 patients relapsed. Treatment-related mortality was 2.9%. With a median follow-up of 36.0 (0.5-119.0) months, 3-year overall survival (OS) rate was (88.9±2.4) % and event free survival (EFS) rate was (87.9±2.6) % for all patients. 3-year EFS rates were (96.9±2.1) %, (90.9±3.9) % and (73.4±6.5) % for Group C1, C2 and C3 respectively, and that of Group C3 was significantly lower than that of Group C1 (χ(2)=12.939, P=0.001) and Group C2 (χ(2)=6.302, P=0.036) . The 3-year EFS rates were (79.3±6.8) % and (44.4±16.6) % for patients in group C3 treated with chemotherapy combined with rituximab and chemotherapy alone (χ(2)=5.972, P=0.015) . Multivariable Cox regression analysis showed that Stage Ⅳ (including B-ALL) , residual diseases in mid-term evaluation were independent unfavorable prognostic factors[HR=4.241 (95%CI 1.163-27.332) , P=0.026; HR=32.184 (95%CI 11.441-99.996) , P<0.001]. Conclusions: The modified LMB89 Group C regimen has ideal effect for the children with high-risk Burkitt lymphoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt , Adolescente , Linfoma de Burkitt/tratamento farmacológico , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos
11.
Cancer Radiother ; 23(6-7): 496-499, 2019 Oct.
Artigo em Francês | MEDLINE | ID: mdl-31471251

RESUMO

Stereotactic radiotherapy of oligometastases, mono- or hypofractionated, represents a fundamental change in the practice of the specialty as it was developed for a century. Despite the great heterogeneity of sites, techniques, and doses, most studies found a high local control rate, around 70 to 90% at 2 years, and reduced toxicity, around 5% of grade 3 at 2 years. Four main phase II and III trials are underway in France. Future research concerns the association of stereotactic radiotherapy with immunotherapy or different conventional chemotherapy protocols, the identification of the best clinical presentations, and optimization of fractionation and biological dose for poor prognosis localizations.


Assuntos
Ensaios Clínicos Fase II como Assunto , Ensaios Clínicos Fase III como Assunto , Neoplasias/radioterapia , Radiocirurgia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ósseas/radioterapia , Neoplasias Ósseas/secundário , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/radioterapia , Terapia Combinada/métodos , Previsões , França , Humanos , Imunoterapia , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/radioterapia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Metástase Neoplásica , Neoplasias/patologia , Neoplasias/terapia , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/radioterapia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/radioterapia
12.
Cancer Treat Rev ; 79: 101887, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31491661

RESUMO

Small cell lung cancer (SCLC) was defined as a "recalcitrant cancer" because of its dismal prognosis and lack of outcome improvements in the last 30 years. Immunotherapy with checkpoint inhibitors revolutionized treatment in many cancer types and results from the IMpower133 study, a double-blind placebo-controlled phase III trial, showed overall survival benefit for atezolizumab when added to standard platinum-etoposide chemotherapy in first-line SCLC setting for the first time since years. Trials with other checkpoint inhibitors, e.g. pembrolizumab, durvalumab, nivolumab and ipilimumab, are ongoing in various settings, but, to date, there are no defined factors to identify patients who are more likely to benefit from such treatments. This review summarizes results of immunotherapy trials in SCLC for first-line, maintenance and further-line therapies for single-agents and combinations with checkpoint inhibitors. Predictive factors from these trials are reviewed in order to identify their clinical value, with particular emphasis on PD-L1 expression on both tumor cells and in stroma, especially in pembrolizumab-treated patients, and tumor mutational burden, for patients treated with the ipilimumab and nivolumab combination.


Assuntos
Imunoterapia , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/terapia , Carcinoma de Pequenas Células do Pulmão/imunologia , Carcinoma de Pequenas Células do Pulmão/terapia , Antineoplásicos Imunológicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais , Ensaios Clínicos como Assunto , Terapia Combinada , Humanos , Imunomodulação/efeitos dos fármacos , Imunoterapia/métodos , Imunoterapia/tendências , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Terapia de Alvo Molecular , Carcinoma de Pequenas Células do Pulmão/mortalidade , Carcinoma de Pequenas Células do Pulmão/patologia , Resultado do Tratamento
13.
Anticancer Res ; 39(9): 4597-4602, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519556

RESUMO

Our previous review of the literature assessed the existing knowledge (until 2000) about the possible link between angiotensin-converting enzyme inhibitors (ACEIs) and factors influencing the development of malignancies. We reviewed the literature for reports of statistical associations (or lack thereof) between ACEi treatment and incidence of specific cancers (e.g. breast, gastrointestinal, and skin). We concluded then that results from the epidemiological studies are conflicting, even taking the different methodology and endpoints into consideration, and thus inconclusive. Further investigation is needed beyond the observation period of most of these studies, and additional experimental studies are needed also to study the mechanisms by which agents blocking the renin-angiotensin system may obtain their inhibitory effect on tumor growth and metastasis. The present review elaborates further with more recent evidence from numerous human clinical studies from the past two decades (including large epidemiological studies, and long-term prospective and retrospective studies) on a protective association between ACEi treatment and the prognosis of patients with specific cancer types, malignancy characteristics or stage. Moreover, treatment with ACEI/angiotensin receptor blockers represents an adjuvant therapy with synergistic effects to chemotherapy and may improve patient outcomes (i.e. progression-free survival, and prolonged overall survival) in different types of cancers.


Assuntos
Neoplasias/metabolismo , Neoplasias/mortalidade , Sistema Renina-Angiotensina/efeitos dos fármacos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/farmacologia , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Animais , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Estudos Clínicos como Assunto , Modelos Animais de Doenças , Progressão da Doença , Humanos , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Neoplasias/etiologia , Prognóstico , Resultado do Tratamento
14.
Anticancer Res ; 39(9): 4619-4625, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519559

RESUMO

Cancer patients are at risk for both venous and arterial thrombotic events. Accumulating evidence suggests a link between cancer and arterial thrombosis events. The pathophysiology of arterial thrombosis in cancer is complex and multifactorial. The risk of arterial thrombosis in cancer patients relies on individual risk factors, on cancer-related hypercoagulability, on anticancer drugs and radiotherapy often via a common underlying mechanism of endothelial dysfunction. This review describes the mechanisms involved in the development of arterial thrombotic events and their clinical manifestations. Furthermore, it provides an overview on therapeutic agents associated with arterial thrombosis.


Assuntos
Artérias/patologia , Neoplasias/complicações , Trombose/etiologia , Animais , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Gerenciamento Clínico , Humanos , Neoplasias/epidemiologia , Neoplasias/patologia , Neoplasias/terapia , Neovascularização Patológica , Radioterapia/efeitos adversos , Radioterapia/métodos , Avaliação de Sintomas , Trombose/diagnóstico , Trombose/epidemiologia
15.
Anticancer Res ; 39(9): 4667-4671, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519565

RESUMO

BACKGROUND/AIM: Liver metastasis in colorectal-cancer is a recalcitrant disease. To develop precision individualized therapy of this disease, we developed a patient-derived orthotopic xenograft (PDOX) model of colorectal-cancer liver metastasis. In the present report, we evaluated the efficacy of oral recombinant methioninase (o-rMETase) in combination with 5-fluorouracil (5-FU) and oxaliplatinum (OXA) on the colorectal-cancer liver metastasis PDOX mouse model. MATERIALS AND METHODS: Colorectal-cancer liver metastasis PDOX models were randomized into three groups of seven mice. Group 1, untreated control with phosphate buffered saline (PBS); Group 2, treated with 5-FU + OXA; and Group 3, treated with 5-FU + OXA + o-rMETase. RESULTS: The colorectal-cancer liver metastasis PDOX model was resistant to 5-FU + OXA (p=0.83 at day 15 of treatment, Group 2). In contrast, the colorectal-cancer liver metastasis PDOX model was arrested by o-rMETase combined with 5-FU + OXA (p<0.01 at day 15, Group 3). No significant body-weight differences were observed among the groups. CONCLUSION: The combination therapy of 5-FU and OXA with o-rMETase can overcome the resistance of first line drugs for colorectal-cancer liver metastasis.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Animais , Antimetabólitos Antineoplásicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Liases de Carbono-Enxofre/administração & dosagem , Neoplasias Colorretais/tratamento farmacológico , Modelos Animais de Doenças , Fluoruracila/administração & dosagem , Humanos , Neoplasias Hepáticas/patologia , Camundongos , Oxaliplatina/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Anticancer Res ; 39(9): 4781-4786, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519579

RESUMO

BACKGROUND/AIM: Osteosarcoma is a rare but recalcitrant type of bone cancer. To discover an effective therapy for osteosarcoma, we used a patient-derived orthotopic xenograft (PDOX) mouse model. A PDOX mouse model has been established for all major cancer types. Strong synergistic efficacy of sorafenib (SFN) and everolimus (EVL) has been demonstrated in several cancers. In the present study, we examined the efficacy of a SFN and EVL combination on a doxorubicin (DOX)-resistant osteosarcoma PDOX. MATERIALS AND METHODS: The osteosarcoma PDOX models were randomly divided into five treatment groups, each containing six mice: Control; DOX; SFN; EVL; and a combination of SFN and EVL. Mice were treated for 14 days. To observe the efficacy of these treatments, tumor size and body weight were measured, and histological sections were analyzed. RESULTS: Tumor growth regression was observed only in the mice treated with the combination of SFN-EVL. Histological analysis revealed necrosis with degenerative changes in tumors treated with a combination of SFN-EVL. CONCLUSION: A SFN-EVL combination could be a novel effective treatment option for osteosarcoma.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Osteossarcoma/patologia , Animais , Modelos Animais de Doenças , Progressão da Doença , Doxorrubicina/farmacologia , Everolimo/administração & dosagem , Humanos , Camundongos , Osteossarcoma/tratamento farmacológico , Sorafenibe/administração & dosagem , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Anticancer Res ; 39(9): 4911-4916, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519595

RESUMO

BACKGROUND/AIM: The occurrence of somatic transformation in germ cell tumour (GCT) is rare, with increased incidence in teratomatous tumours. The aim of this study was to understand the clinical outcomes of patients with metastatic GCT with somatic transformation. MATERIALS AND METHODS: A retrospective study was conducted in two tertiary cancer centres in London. Between 1998 and 2016, 30 cases of somatic transformation in GCT treated at the Mount Vernon Cancer Centre and St. Bartholomew's Hospital were identified. The median age at diagnosis was 34 years (range=18-56 years). The histological diagnosis at transformation was rhabdomyosarcoma, sarcomatoid yolk sac, sarcoma (non-specified), clear cell carcinoma, adenocarcinoma and primitive neuro ectodermal tumour (PNET). RESULTS: The 5-year survival rate of all patients was 47%, and that of patients with testicular primary (n=26 patients) was 37%. CONCLUSION: Somatic transformation component in testicular GCTs is generally considered to be an adverse prognostic factor, however, a reasonable 5-year overall survival rate (87.5%) was observed in patients who present with this at first diagnosis.


Assuntos
Transformação Celular Neoplásica/genética , Mutação , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Embrionárias de Células Germinativas/secundário , Neoplasias Testiculares/genética , Neoplasias Testiculares/secundário , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Suscetibilidade a Doenças , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/terapia , Retratamento , Análise de Sobrevida , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/terapia , Resultado do Tratamento , Adulto Jovem
18.
Anticancer Res ; 39(9): 4917-4924, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519596

RESUMO

BACKGROUND/AIM: Recent data highlighted that location of metastatic colorectal cancer (mCRC) may have a prognostic impact and also a predictive value of the outcomes of first-line therapy. MATERIALS AND METHODS: The records of mCRC patients who underwent first-line therapy from 2011 to April 2018 at our Institute were retrospectively reviewed. Progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) according to the primary tumor location were investigated. RESULTS: Overall, 130 patients were eligible. Two-year OS was 82.9% in left-sided colon cancers (LCC) and 67.5% in right-sided (RCC) (p=0.32). One-year mPFS was statistically longer in LCC (46.8% vs. 24.2%, p=0.0005). mPFS was longer in LCC treated with anti-VEGF vs. anti-EGFR (p=0.06). ORR was 51.1% in LCC, 25% in RCC (p=0.008). Overall, 11 complete responses all in LCC were observed (p=0.03). CONCLUSION: Tumor location has a prognostic impact and might influence the outcomes of mCRC patients.


Assuntos
Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/terapia , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
19.
Anticancer Res ; 39(9): 4925-4931, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519597

RESUMO

BACKGROUND/AIM: Diffuse large B-cell lymphoma (DLBCL) is an aggressive malignancy where antioxidant enzyme peroxiredoxin 6 (Prx6) has previously been associated with adverse outcomes. Its systemic effects in DLBCL are unknown. MATERIALS AND METHODS: This study included 53 patients with DLBCL, five patients with primary central nervous system lymphoma (PCNSL) and 20 healthy controls. The expression of Prx6 was evaluated immunohistochemically in DLBCL tissue samples and compared to its expression in blood serum. RESULTS: Prx6 expression was the highest in healthy controls, followed by DLBCL patients and PCNSL patients. Febrile neutropenic infection after the first treatment course was associated with low pre-treatment Prx6 serum levels (<14 ng/ml) (p=0.025, OR=8.615, 95% confidence interval=1.032-71.933). Serum levels of Prx6 recovered after treatment (p=0.006). CONCLUSION: Patients with low Prx6 levels might be more prone to treatment-related adverse effects through elevated levels of oxidative stress.


Assuntos
Infecção/etiologia , Linfoma Difuso de Grandes Células B/sangue , Linfoma Difuso de Grandes Células B/complicações , Neutropenia/complicações , Neutropenia/etiologia , Peroxirredoxina VI/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores , Feminino , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Medição de Risco , Fatores de Risco
20.
Anticancer Res ; 39(9): 4987-4993, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519605

RESUMO

BACKGROUND/AIM: For immune checkpoint inhibitor (ICI)-pretreated patients, docetaxel and ramucirumab (DOC+RAM) combination therapy may be more effective compared to patients not receiving ICI treatment. PATIENTS AND METHODS: From June 2013 to July 2018, 39 patients with advanced/recurrent non-small cell lung cancer underwent DOC+RAM therapy. We analyzed the efficacy and safety of DOC+RAM therapy based on the presence (pre-ICI+) or absence (pre-ICI-) of ICI pretreatment history. RESULTS: Of the 39 patients treated with DOC+RAM, we identified 18 (46%) pre-ICI+ patients. Overall response rates for DOC+RAM concerning pre-ICI+ and pre-ICI- patients were 38.9% vs. 19.0%, respectively. Median progression-free survival (PFS) was 5.7 vs. 2.3 months [hazard ratio(HR)=0.36; 95% confidence interval (CI)=0.16-0.80]. Adverse events such as fever, myalgia, arthritis, pleural effusion, and pneumonitis tended to be increased in pre-ICI+ patients. CONCLUSION: Despite increased toxicity concerns, DOC+RAM therapy in pre-ICI+ patients showed a trend for tumor regression improvement and statistically significant prolongation of PFS.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Idoso , Anticorpos Monoclonais/administração & dosagem , Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Docetaxel/administração & dosagem , Sinergismo Farmacológico , Feminino , Humanos , Imunomodulação/efeitos dos fármacos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
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