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1.
Cancer Commun (Lond) ; 44(1): 127-172, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38160327

RESUMO

The 2023 update of the Chinese Society of Clinical Oncology (CSCO) Clinical Guidelines for Gastric Cancer focuses on standardizing cancer diagnosis and treatment in China, reflecting the latest advancements in evidence-based medicine, healthcare resource availability, and precision medicine. These updates address the differences in epidemiological characteristics, clinicopathological features, tumor biology, treatment patterns, and drug selections between Eastern and Western gastric cancer patients. Key revisions include a structured template for imaging diagnosis reports, updated standards for molecular marker testing in pathological diagnosis, and an elevated recommendation for neoadjuvant chemotherapy in stage III gastric cancer. For advanced metastatic gastric cancer, the guidelines introduce new recommendations for immunotherapy, anti-angiogenic therapy and targeted drugs, along with updated management strategies for human epidermal growth factor receptor 2 (HER2)-positive and deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) patients. Additionally, the guidelines offer detailed screening recommendations for hereditary gastric cancer and an appendix listing drug treatment regimens for various stages of gastric cancer. The 2023 CSCO Clinical Guidelines for Gastric Cancer updates are based on both Chinese and international clinical research and expert consensus to enhance their applicability and relevance in clinical practice, particularly in the heterogeneous healthcare landscape of China, while maintaining a commitment to scientific rigor, impartiality, and timely revisions.


Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Oncologia , Imunoterapia , Terapia Neoadjuvante , China
2.
NPJ Precis Oncol ; 7(1): 93, 2023 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-37717087

RESUMO

As a highly lethal adenocarcinoma of the hepatobiliary system, outcomes for cholangiocarcinoma (CCA) patients remain prominently poor with a 5-year survival of <10% due to the lack of effective treatment modalities. Targeted therapeutics for CCA are limited and surgical resection of CCA frequently suffers from a high recurrence rate. Here we report two effective targeted therapeutics in this preclinical study for CCA. We first performed a quantitative and unbiased screening of cancer-related antigens using comparative flow cytometry in a panel of human CCA cell lines, and identified intercellular adhesion molecule-1 (ICAM1) as a therapeutic target for CCA. After determining that ICAM1 has the ability to efficiently mediate antibody internalization, we constructed two ICAM1 antibody-drug conjugates (ADCs) by conjugating ICAM1 antibodies to different cytotoxic payloads through cleavable chemical linkers. The efficacies of two ICAM1 ADCs have been evaluated in comparison with the first-line chemodrug Gemcitabine in vitro and in vivo, and ICAM1 antibodies coupled with warhead DX-8951 derivative (DXd) or monomethyl auristatin E (MMAE) elicit a potent and consistent tumor attenuation. In summary, this study paves the road for developing a promising targeted therapeutic candidate for clinical treatment of CCA.

3.
Lancet Oncol ; 24(7): 772-782, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37276871

RESUMO

BACKGROUND: HER2 is overexpressed or amplified in a subset of biliary tract cancer. Zanidatamab, a bispecific antibody targeting two distinct HER2 epitopes, exhibited tolerability and preliminary anti-tumour activity in HER2-expressing or HER2 (also known as ERBB2)-amplified treatment-refractory biliary tract cancer. METHODS: HERIZON-BTC-01 is a global, multicentre, single-arm, phase 2b trial of zanidatamab in patients with HER2-amplified, unresectable, locally advanced, or metastatic biliary tract cancer with disease progression on previous gemcitabine-based therapy, recruited at 32 clinical trial sites in nine countries in North America, South America, Asia, and Europe. Eligible patients were aged 18 years or older with HER2-amplified biliary tract cancer confirmed by in-situ hybridisation per central testing, at least one measurable target lesion per Response Evaluation Criteria in Solid Tumours (version 1.1), and an Eastern Cooperative Oncology Group performance status of 0 or 1. Patients were assigned into cohorts based on HER2 immunohistochemistry (IHC) score: cohort 1 (IHC 2+ or 3+; HER2-positive) and cohort 2 (IHC 0 or 1+). Patients received zanidatamab 20 mg/kg intravenously every 2 weeks. The primary endpoint was confirmed objective response rate in cohort 1 as assessed by independent central review. Anti-tumour activity and safety were assessed in all participants who received any dose of zanidatamab. This trial is registered with ClinicalTrials.gov, NCT04466891, is ongoing, and is closed to recruitment. FINDINGS: Between Sept 15, 2020, and March 16, 2022, 87 patients were enrolled in HERIZON-BTC-01: 80 in cohort 1 (45 [56%] were female and 35 [44%] were male; 52 [65%] were Asian; median age was 64 years [IQR 58-70]) and seven in cohort 2 (five [71%] were male and two [29%] were female; five [71%] were Asian; median age was 62 years [IQR 58-77]). At the time of the data cutoff (Oct 10, 2022), 18 (21%) patients (17 in cohort 1 and one in cohort 2) were continuing to receive zanidatamab; 69 (79%) discontinued treatment (radiographic progression in 64 [74%] patients). The median duration of follow-up was 12·4 months (IQR 9·4-17·2). Confirmed objective responses by independent central review were observed in 33 patients in cohort 1 (41·3% [95% CI 30·4-52·8]). 16 (18%) patients had grade 3 treatment-related adverse events; the most common were diarrhoea (four [5%] patients) and decreased ejection fraction (three [3%] patients). There were no grade 4 treatment-related adverse events and no treatment-related deaths. INTERPRETATION: Zanidatamab demonstrated meaningful clinical benefit with a manageable safety profile in patients with treatment-refractory, HER2-positive biliary tract cancer. These results support the potential of zanidatamab as a future treatment option in HER2-positive biliary tract cancer. FUNDING: Zymeworks, Jazz, and BeiGene.


Assuntos
Antineoplásicos , Neoplasias dos Ductos Biliares , Neoplasias do Sistema Biliar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias dos Ductos Biliares/tratamento farmacológico , Neoplasias do Sistema Biliar/tratamento farmacológico , Neoplasias do Sistema Biliar/genética , Gencitabina
4.
BMC Cancer ; 23(1): 308, 2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37016303

RESUMO

BACKGROUND: The Neo-REGATTA study evaluated the effectiveness and safety of Docetaxel, oxaliplatin, and S-1 (DOS regimen) followed by radical resection vs. chemotherapy in advanced gastric adenocarcinoma patients with single non-curable factor. METHODS: This cohort study prospectively enrolled advanced gastric adenocarcinoma patients with single non-curable factor between November 2017 and June 2021. Patients without progression after four cycles of DOS were divided into resection group and chemotherapy group. The outcomes included overall survival (OS), progression-free survival (PFS) and safety. Effectiveness analysis was also performed by propensity score matching (PSM). RESULTS: A total of 73 patients were enrolled and 13 patients were withdrawn due to disease progression after 4 cycles of DOS. Afterwards, 35 and 25 participants were in the resection and chemotherapy groups, respectively. After a median follow-up time of 30.0 months, the median PFS and OS were 9.0 months, and 18.0 months for the chemotherapy group, but not reached in the resection group. After PSM, 19 matched participants were in each group, and the median PFS and OS were longer in resection group than that in chemotherapy group. The most common grade 3 or 4 adverse events both in the resection group and chemotherapy groups were neutropenia (5.7%, 8.0%) and leukopenia (5.7%, 8.0%). CONCLUSIONS: Radical resection might provide survival benefit compared with continuous chemotherapy alone in advanced gastric adenocarcinoma patients who had a disease control after DOS, with a good safety profile. TRIAL REGISTRATION: The study protocol was registered on ClinicalTrial.gov (NCT03001726, 23/12/2016).


Assuntos
Adenocarcinoma , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Docetaxel/uso terapêutico , Oxaliplatina/uso terapêutico , Terapia Neoadjuvante , Estudos de Coortes , Estudos Prospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/cirurgia , Adenocarcinoma/patologia
5.
Curr Oncol ; 29(11): 8235-8243, 2022 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-36354710

RESUMO

Common treatment methods for malignant tumors include surgery, chemotherapy, radiotherapy, immunotherapy, targeted therapy, etc., among which chemotherapy plays an important role. However, chemotherapy brings corresponding side effects while killing tumor cells, and nausea and vomiting are the most common adverse reactions induced by chemotherapy. It not only affects the patient's appetite, resulting in malnutrition and electrolyte disturbances, but also reduces the patient's compliance with treatment, which further aggravates the disease. Thus, it is important to quickly prevent and cure nausea and vomiting induced by chemotherapy (CINV). In addition, with the continuous development of medicine, more and more antiemetic drugs have been developed. At present, the most common antiemetic agents for chemotherapy-induced nausea and vomiting are NK-1R antagonists, 5-HT3R antagonists, and dexamethasone. Surprisingly, olanzapine, often used as a psychotropic drug, has been found to be an effective antiemetic and is similar to other regimens on the safety of medicine. However, although there are numerous studies on the antiemetic effects of olanzapine, its comprehensive application remains unclear. Therefore, this review will elaborate the antiemetic effect of olanzapine in terms of the antiemetic mechanism and the safety, economic cost, dose, administration time, and drug delivery aspects.


Assuntos
Antieméticos , Antineoplásicos , Humanos , Olanzapina/uso terapêutico , Antieméticos/farmacologia , Antieméticos/uso terapêutico , Preparações Farmacêuticas , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Náusea/prevenção & controle , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Vômito/prevenção & controle , Antineoplásicos/efeitos adversos
6.
Clin Cancer Res ; 28(19): 4232-4239, 2022 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-35929990

RESUMO

PURPOSE: To compare the efficacy and safety of high-dose vitamin C plus FOLFOX ± bevacizumab versus FOLFOX ± bevacizumab as first-line treatment in patients with metastatic colorectal cancer (mCRC). PATIENTS AND METHODS: Between 2017 and 2019, histologically confirmed patients with mCRC (n = 442) with normal glucose-6-phosphate dehydrogenase status and no prior treatment for metastatic disease were randomized (1:1) into a control (FOLFOX ± bevacizumab) and an experimental [high-dose vitamin C (1.5 g/kg/d, intravenously for 3 hours from D1 to D3) plus FOLFOX ± bevacizumab] group. Randomization was based on the primary tumor location and bevacizumab prescription. RESULTS: The progression-free survival (PFS) of the experimental group was not superior to the control group [median PFS, 8.6 vs. 8.3 months; HR, 0.86; 95% confidence interval (CI), 0.70-1.05; P = 0.1]. The objective response rate (ORR) and overall survival (OS) of the experimental and control groups were similar (ORR, 44.3% vs. 42.1%; P = 0.9; median OS, 20.7 vs. 19.7 months; P = 0.7). Grade 3 or higher treatment-related adverse events occurred in 33.5% and 30.3% of patients in the experimental and control groups, respectively. In prespecified subgroup analyses, patients with RAS mutation had significantly longer PFS (median PFS, 9.2 vs. 7.8 months; HR, 0.67; 95% CI, 0.50-0.91; P = 0.01) with vitamin C added to chemotherapy than with chemotherapy only. CONCLUSIONS: High-dose vitamin C plus chemotherapy failed to show superior PFS compared with chemotherapy in patients with mCRC as first-line treatment but may be beneficial in patients with mCRC harboring RAS mutation.


Assuntos
Antineoplásicos , Neoplasias do Colo , Neoplasias Colorretais , Neoplasias Retais , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ácido Ascórbico/efeitos adversos , Bevacizumab , Neoplasias do Colo/tratamento farmacológico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Fluoruracila , Glucosefosfato Desidrogenase/uso terapêutico , Humanos , Leucovorina , Neoplasias Retais/etiologia
7.
Front Pharmacol ; 13: 911663, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35656301

RESUMO

Trametes robiniophila Murr (TRM) is a traditional Chinese medicine which has been used in clinics for enhancing immunity and improving the efficacy of chemotherapy. However, the mechanisms of action of TRM are unknown. In the previous study, we found that the Trametes robiniophila Murr n-butanol extract (TRMBE) comprises the major bioactive components of TRM. In the present study, we aimed to assess the combinational effects of TRMBE and 5-fluorouracil (5-FU) on the treatment of gastric cancer (GC) and explore its mechanism of action. It was found that TRMBE significantly potentiated the anticancer activity of 5-FU and prolonged the survival time of mice bearing Mouse Forestomach Carcinoma (MFC) xenograft tumors. We observed that the combination of TRMBE and 5-FU decreased the risk of liver metastasis in vivo. Furthermore, the combination of TRMBE and 5-FU reduced the levels of immune cytokines IL-6, IL-10, and TGF-ß and increased the level of IFN-γ in peripheral blood. This combination therapy also significantly decreased the levels of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) and PD-1-positive CD8+ T cells and increased the levels of NK cells in tumor microenvironment (TME). However, TRMBE treatment was unable to enhance the chemosensitivity of GC to 5-FU in vivo after the depletion of CD8+ T and NK cells. Taken together, our results demonstrate that TRMBE can reshape the TME of GC by regulating PMN-MDSCs, CD8+ T cells, and NK cells, therefore improving the therapeutic effects of 5-FU. This study suggests that the combination of TRMBE and 5-FU could enhance immunity and could be a promising approach for GC treatment.

8.
Cancer Commun (Lond) ; 42(4): 314-326, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35212487

RESUMO

BACKGROUND: There is no consensus on whether triplet regimen is better than doublet regimen in the first-line treatment of advanced gastric cancer (AGC). We aimed to compare the efficacy and safety of oxaliplatin plus capecitabine (XELOX) and epirubicin, oxaliplatin, plus capecitabine (EOX) regimens in treating AGC. METHODS: This phase III trial enrolled previously untreated patients with AGC who were randomly assigned to receive the XELOX or EOX regimen. The primary endpoint was non-inferiority in progression-free survival (PFS) for XELOX as compared with EOX on an intention-to-treat basis. RESULTS: Between April 10, 2015 and August 20, 2020, 448 AGC patients were randomized to receive XELOX (n = 222) or EOX (n = 226). The median PFS (mPFS) was 5.0 months (95% confidence interval [CI] = 4.5-6.0 months) in the XELOX arm and 5.5 months (95% CI = 5.0-6.0 months) in the EOX arm (hazard ratio [HR] = 0.989, 95% CI = 0.812-1.203; Pnon-inferiority = 0.003). There was no significant difference in median overall survival (mOS) (12.0 vs. 12.0 months, P = 0.384) or objective response rate (37.4% vs. 45.1%, P = 0.291) between the two groups. In patients with poorly differentiated adenocarcinoma and liver metastasis, the EOX arm had a significantly longer mOS (P = 0.021) and a trend of longer mPFS (P = 0.073) than the XELOX arm. The rate of grade 3/4 adverse events (AEs) was 42.2% (90/213) in the XELOX arm and 72.5% (156/215) in the EOX arm (P = 0.001). The global health-related quality of life (QoL) score was significantly higher in the XELOX arm than in the EOX arm during chemotherapy. CONCLUSIONS: This non-inferiority trial demonstrated that the doublet regimen was as effective as the triplet regimen and had a better safety profile and QoL as a first-line treatment for AGC patients. However, the triplet regimen might have a survival advantage in patients with poorly differentiated adenocarcinoma and liver metastasis.


Assuntos
Adenocarcinoma , Neoplasias Hepáticas , Neoplasias Gástricas , Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Oxaliplatina , Oxaloacetatos , Estudos Prospectivos , Qualidade de Vida , Neoplasias Gástricas/patologia
9.
J Cancer Res Clin Oncol ; 148(3): 673-684, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33864522

RESUMO

BACKGROUND: Establish patient-derived tumor xenograft (PDTX) from advanced GICs and assess the clinical value and applicability of PDTX for the treatment of advanced gastrointestinal cancers. METHODS: Patients with advanced GICs were enrolled in a registered multi-center clinical study (ChiCTR-OOC-17012731). The performance of PDTX was evaluated by analyzing factors that affect the engraftment rate, comparing the histological consistency between primary tumors and tumorgrafts, examining the concordance between the drug effectiveness in PDTXs and clinical responses, and identifying genetic variants and other factors associated with prognosis. RESULTS: Thirty-three patients were enrolled in the study with the engraftment rate of 75.8% (25/33). The success of engraftment was independent of age, cancer types, pathological stages of tumors, and particularly sampling methods. Tumorgrafts retained the same histopathological characteristics as primary tumors. Forty-nine regimens involving 28 drugs were tested in seventeen tumorgrafts. The median time for drug testing was 134.5 days. Follow-up information was obtained about 10 regimens from 9 patients. The concordance of drug effectiveness between PDTXs and clinical responses was 100%. The tumor mutation burden (TMB) was correlated with the effectiveness of single drug regimens, while the outgrowth time of tumorgrafts was associated with the effectiveness of combined regimens. CONCLUSION: The engraftment rate in advanced GICs was higher than that of other cancers and meets the acceptable standard for applying personalized therapeutic strategies. Tumorgrafts from PDTX kept attributes of the primary tumor. Predictions from PDTX modeling closely agreed with clinical drug responses. PDTX may already be clinically applicable for personalized medication in advanced GICs.


Assuntos
Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Neoplasias Gastrointestinais/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Adulto , Idoso , Animais , Feminino , Seguimentos , Neoplasias Gastrointestinais/genética , Neoplasias Gastrointestinais/patologia , Humanos , Masculino , Camundongos Endogâmicos NOD , Pessoa de Meia-Idade , Medicina de Precisão , Prognóstico , Estudos Prospectivos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Cancer Commun (Lond) ; 41(8): 747-795, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34197702

RESUMO

There exist differences in the epidemiological characteristics, clinicopathological features, tumor biological characteristics, treatment patterns, and drug selections between gastric cancer patients from the Eastern and Western countries. The Chinese Society of Clinical Oncology (CSCO) has organized a panel of senior experts specializing in all sub-specialties of gastric cancer to compile a clinical guideline for the diagnosis and treatment of gastric cancer since 2016 and renews it annually. Taking into account regional differences, giving full consideration to the accessibility of diagnosis and treatment resources, these experts have conducted expert consensus judgment on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes in China. The 2021 CSCO Clinical Practice Guidelines for Gastric Cancer covers the diagnosis, treatment, follow-up, and screening of gastric cancer. Based on the 2020 version of the CSCO Chinese Gastric Cancer guidelines, this updated guideline integrates the results of major clinical studies from China and overseas for the past year, focused on the inclusion of research data from the Chinese population for more personalized and clinically relevant recommendations. For the comprehensive treatment of non-metastatic gastric cancer, attentions were paid to neoadjuvant treatment. The value of perioperative chemotherapy is gradually becoming clearer and its recommendation level has been updated. For the comprehensive treatment of metastatic gastric cancer, recommendations for immunotherapy were included, and immune checkpoint inhibitors from third-line to the first-line of treatment for different patient groups with detailed notes are provided.


Assuntos
Neoplasias Gástricas , China , Humanos , Oncologia , Sociedades Médicas , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/tratamento farmacológico
11.
J Surg Oncol ; 123(8): 1708-1715, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33684248

RESUMO

OBJECTIVE: This study aimed to investigate alterations in pre- and post-neoadjuvant chemotherapy (NACT) tumor-infiltrating immune cells and subsequent evaluation of the predictive and prognostic value of these changes in gastric cancer (GC). METHODS: Fifty patients with GC underwent three cycles of S-1 and oxaliplatin (SOX regimen)-NACT. Paired samples from tumor lesions before and after NACT were available for all patients participating in the study. Immunohistochemistry was performed for T cell subsets (CD3+ and CD8+ ) and macrophages (CD68+ and CD163+ ). RESULTS: After NACT, the average expression levels of CD3, CD8, CD68, and CD163 were significantly increased (p < .001). However, neither expression levels pre- nor post-chemotherapy correlated with treatment response. Multivariate Cox regression analysis demonstrated that upregulation of CD8/CD3 levels (hazard ratio [HR] = 0.117; 95% confidence interval [CI] = 0.031-0.446; p = 0.002) and CD163 levels after chemotherapy (HR = 2.258; 95% CI = 1.047-4.867; p = 0.038) were independent prognostic factors of overall survival. CONCLUSION: Chemotherapy in GC is useful to induce CD3+ and CD8+ T lymphocytes as well as CD68+ and CD163+ macrophages in the tumor microenvironment in combination with its direct cytotoxic effects. These results indicate that chemotherapy may play a role in tumor immune microenvironment remodeling.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Microambiente Tumoral , Adulto , Idoso , Feminino , Humanos , Linfócitos do Interstício Tumoral , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante , Oxaliplatina/uso terapêutico , Estudos Retrospectivos , Neoplasias Gástricas/metabolismo , Adulto Jovem
12.
Asian Pac J Cancer Prev ; 15(16): 6559-64, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25169487

RESUMO

OBJECTIVE: To evaluate the efficacy and safety of bevacizumab in the treatment of patients with metastatic colorectal cancer (mCRC). METHODS: In a single-center, observational study of 91 Chinese patients with mCRC who received bevacizumab in combination with chemotherapy was conducted. OBJECTIVE response rates (ORRs), progression-free survival (PFS), overall survival (OS) and adverse events were recorded, and the relationships between various clinical factors and PFS or OS were evaluated by Cox proportional hazards models. RESULTS: Treatment with bevacizumab and chemotherapy was effective and tolerable. Univariate analysis showed that PFS and OS were significantly associated with the Eastern Cooperative Oncology Group performance status (ECOG- PS) score, duration of bevacizumab exposure, and whether chemotherapy was continued after discontinuation of bevacizumab treatment. A multivariate analysis showed that the duration of bevacizumab exposure and whether chemotherapy was continued after discontinuation of bevacizumab were independent prognostic factors for PFS and OS. CONCLUSION: In Chinese mCRC population, the shorter the duration of exposure to bevacizumab and chemotherapy, the worse the prognosis is.


Assuntos
Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bevacizumab , Camptotecina/efeitos adversos , Camptotecina/análogos & derivados , Camptotecina/uso terapêutico , China , Neoplasias Colorretais/mortalidade , Intervalo Livre de Doença , Feminino , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Leucovorina/efeitos adversos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/efeitos adversos , Compostos Organoplatínicos/uso terapêutico , Resultado do Tratamento , Adulto Jovem
13.
World J Gastroenterol ; 18(8): 736-45, 2012 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-22371633

RESUMO

In the past 15 years, we have seen few therapeutic advances for patients with pancreatic cancer, which is the fourth leading cause of cancer-related death in the United States. Currently, only about 6% of patients with advanced disease respond to standard gemcitabine therapy, and median survival is only about 6 mo. Moreover, phase III trials have shown that adding various cytotoxic and targeted chemotherapeutic agents to gemcitabine has failed to improve overall survival, except in cases in which gemcitabine combined with erlotinib show minimal survival benefit. Several meta-analyses have shown that the combination of gemcitabine with either a platinum analog or capecitabine may lead to clinically relevant survival prolongation, especially for patients with good performance status. Meanwhile, many studies have focused on the pharmacokinetic modulation of gemcitabine by fixed-dose administration, and metabolic or transport enzymes related to the response and toxicity of gemcitabine. Strikingly, a phase III trial in 2010 showed that, in comparison to gemcitabine alone, the FOLFIRINOX regimen in patients with advanced disease and good performance status, produced better median overall survival, median progression-free survival, and objective response rates. This regimen also resulted in greater, albeit manageable toxicity.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Desoxicitidina/análogos & derivados , Metástase Neoplásica/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Benzenossulfonatos/uso terapêutico , Ensaios Clínicos como Assunto , Desoxicitidina/uso terapêutico , Intervalo Livre de Doença , Cloridrato de Erlotinib , Humanos , Metanálise como Assunto , Niacinamida/análogos & derivados , Compostos de Fenilureia , Inibidores de Proteínas Quinases/uso terapêutico , Piridinas/uso terapêutico , Quinazolinas/uso terapêutico , Sorafenibe , Gencitabina
14.
Mol Biol Rep ; 39(5): 5459-64, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22207169

RESUMO

Anti-tumor activity and mechanism of matrine is evaluated and investigated. MTT assay showed that the matrine was able to inhibit gastric cancer cell line MNK45 in a dose-dependent manner. The concentration required for 50% inhibition (IC50) was found to be 540 µg/ml. This anti-tumor function was achieved through modulation of the NF-κB, XIAP, CIAP, and p-ERK proteins expression in cell line MNK45. By western blot analysis, we found that expression of NF-κB, XIAP, CIAP, and p-ERK proteins in cell line MNK45 would vary with varying concentration of matrine. These protein interactions possibly play a pivotal role in the regulation of apoptosis, for which further detailed analyzes are need. These results overall indicate that matrine can be used as an effective anti-tumor agent in therapy of gastric cancer.


Assuntos
Alcaloides/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Quinolizinas/farmacologia , Neoplasias Gástricas/patologia , Alcaloides/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Proteínas I-kappa B/metabolismo , NF-kappa B/metabolismo , Fosforilação/efeitos dos fármacos , Subunidades Proteicas/metabolismo , Quinolizinas/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Matrinas
15.
Zhonghua Wei Chang Wai Ke Za Zhi ; 13(4): 289-93, 2010 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-20422488

RESUMO

OBJECTIVE: To investigate the expression of multidrug resistance (MDR) gene-associated proteins (MRP) in gastric carcinoma, and their effects on the postoperative adjuvant chemotherapy and the prognosis of patients. METHODS: The expressions of ToPo II, MRP, GST-pi in 99 patients with gastric carcinoma were detected by immunohistochemistry. The expression and its relationship to the pathological data were analyzed. The positive expression of MRP and GST-pi, and the negative expression of ToPo II were considered as risk factors. Patients were divided into two groups: a high risk drug-resistant group (2-3 risk factors) and the low risk drug-resistant group (0-1 risk factors). Postoperative recurrence, survival rate, and efficacy of adjuvant chemotherapy were compared between two groups. RESULTS: The positive rate of ToPo II was 74.7%, and the expression was associated with types and differentiation of the tumor. The positive rate of GST-pi was 49.5%, and the expression was related to the gender and the differentiation. The positive rate of MRP was 40.4%, and there was no relationship between the MRP expression and the pathological finding. There were no significant differences in the recurrence, time to recurrence, and the 5-year survival rate between the positive and negative group of the three proteins (P>0.05). Recurrence was found in 25 cases(55.6%) in the high risk drug-resistant group and the mean time to recurrence was (15.2+/-8.1) months. The time to recurrence was shorter in the low risk drug-resistant group [(21.3+/-11.1) months, P<0.05] , but there was no significant difference in the recurrence rate between two groups (P>0.05). The 5-year survival rate of the high risk drug-resistant group and the low risk drug-resistant group was 44.4% and 55.6% (P>0.05). The 5-year survival rates of patients with or without chemotherapy in the high risk drug-resistant group were 45.8% and 42.9% (P>0.05). The 5-year survival rates of patients with or without chemotherapy in the low risk drug-resistant group were 70.4% and 40.7%. The survival rate of patients with chemotherapy was higher than that of the patients without chemotherapy (P<0.05). CONCLUSIONS: The expression of ToPo II, MRP and GST-pi is associated with the efficacy of postoperative adjuvant chemotherapy. Chemotherapy appears to be more beneficial to patients with low risk drug-resistance.


Assuntos
DNA Topoisomerases Tipo II/metabolismo , Glutationa S-Transferase pi/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Adulto , Idoso , Quimioterapia Adjuvante , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Prognóstico , Neoplasias Gástricas/diagnóstico
16.
Zhonghua Wei Chang Wai Ke Za Zhi ; 12(4): 395-8, 2009 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-19598028

RESUMO

OBJECTIVE: To investigate the relation between protein expression of 4 genes [P53,c-erbB-2,vascular endothelial factors(VEGF) and CD44]and survival rate in stage II( colorectal cancer(CRC) patients without radiochemotherapy after radical resection. METHODS: One hundred and fifty-nine cases of stage II(CRC without radiochemotherapy were enrolled in this study. The clinicopathological date and 5-year follow-up data were reviewed. Streptavidin-peroxidase immunohistochemical technique was used to detect the expression of P53, c-erbB-2, VEGF and CD44 in formalin-fixed, paraffin embedded sections of CRC tissues from above 159 patients. RESULTS: The 5-year survival rate was 82.4%. The rates of positive expression of P53, c-erbB-2, VEGF and CD44 were 58.5%(93/159), 26.4%(42/159), 57.9%(92/159) and 40.0%(54/159) respectively. The 5-year survival rates of positive expression patients were not significantly different with those of negative expression. chi(2) analysis showed that the positive expressions of 4 genes had no relationships with the prognosis. CONCLUSION: The expression of 4 gene proteins has no relationship with the prognosis of stage II( CRC patients without radiochemotherapy after radical resection.


Assuntos
Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Feminino , Seguimentos , Humanos , Receptores de Hialuronatos/metabolismo , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Taxa de Sobrevida , Proteína Supressora de Tumor p53/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
17.
Anticancer Drugs ; 19(10): 1013-8, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18827567

RESUMO

The fluoropyrimidine and platinum-based combination chemotherapy is now widely used as first-line therapy for advanced gastric cancer (AGC). Unfortunately, about half of all patients do not respond to the current first-line chemotherapy and furthermore, most patients who achieve response to first-line chemotherapy eventually experience disease progression. Although there is a need for effective salvage treatment after the failure of first-line chemotherapy, data on the safety and efficacy of second-line treatment in AGC is limited. The current study evaluated an experimental combination regimen of docetaxel (60 mg/m) as an intravenous infusion of less than 1 h, followed by oxaliplatin (130 mg/m) intravenously for less than 2 h. Both drugs were administered on day 1 of a 21-day cycle, in pretreated Chinese patients with AGC. The trial enrolled 48 patients of whom 46 (95.8%) were assessable for response. The median time to progression was 4.4 months (95% confidence interval (CI): 3.4-5.4 months) and the median overall survival was 7.2 months (95% CI: 6.6-12.1 months). Partial response was confirmed in 11 of 48 cases (22.9%; 95% CI: 10.9-34.9%) and no complete responses were seen. Significant hematologic toxicity was noted with grade 3 and grade 4 neutropenia occurring in 21.7 and 4.3% of patients, respectively, as well as grade 3 thrombocytopenia occurring in 4.3% of patients. Grade 3 febrile neutropenia occurred in 6.5% of the patients. There were no treatment-related deaths during on the study. In summary, docetaxel and oxaliplatin have modest activity with predictable hematologic toxicity when given as salvage therapy for Chinese patients treated earlier for AGC. Given the short duration of response more focus should be given to newer biologic agents and triplet regimens.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Adulto , Idoso , Capecitabina , Cisplatino/administração & dosagem , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Docetaxel , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/análogos & derivados , Humanos , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Neoplasias Gástricas/mortalidade , Taxoides/administração & dosagem
18.
Zhonghua Wei Chang Wai Ke Za Zhi ; 9(5): 405-8, 2006 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-17043961

RESUMO

OBJECTIVE: To evaluate the effect of Supportan, an enteral nutrition (EN) specific for tumor patients, on the nutritional status and immune function of late-staged gastric cancer patients undergoing chemotherapy. METHODS: Sixty-six late-staged gastric cancer patients undergoing chemotherapy were randomly divided into EN group (n=33) and control group (n=33). During chemotherapy, the patients in EN group received Supportan and the patients in the control group received basic diet. On the 14th day before chemotherapy and after chemotherapy, nutritional status and cell immune indicators were evaluated. RESULTS: As for nutrition indicators, there were no significant differences in EN group before and after chemotherapy (P > 0.05). Total protein, hemoglobin, prealbumin and transferrin significantly decreased after chemotherapy compared with those before chemotherapy in the control group (P< 0.01). The levels of CD4(+), CD8(+) T cells and CD4/CD8 were significantly increased, and NK cells, serum levels of IL-1, IL-6 were significantly decreased after chemotherapy in EN group (P< 0.01). The levels of IL-6 and TNF-alpha were significantly higher after chemotherapy than those before chemotherapy in the control group(P< 0.01). Curative effects of immune nutrition in EN group were superior to that in the control group, however, the differences were not statistically significant. The incidences of nausea, vomiting and marrow inhibition in Supportan group was lower compared with those in the control group, but with no significant difference. CONCLUSION: Supportan can prevent malnutrition of the late-staged gastric cancer patients undergoing chemotherapy, and improve immune function and alleviate adverse effects of chemotherapy.


Assuntos
Nutrição Enteral , Emulsões Gordurosas Intravenosas/administração & dosagem , Neoplasias Gástricas/imunologia , Neoplasias Gástricas/terapia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Distúrbios Nutricionais/prevenção & controle , Estado Nutricional , Estudos Prospectivos , Adulto Jovem
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