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BACKGROUND: Although dual blockade HER2-based neoadjuvant chemotherapy is associated with excellent outcomes for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, pertuzumab is not available to all patients due to cost. The optimal neoadjuvant chemotherapy for HER2-positive breast cancer in the presence of a single HER2 blockade is unknown. This study aimed to compare the efficacy and safety of epirubicin/cyclophosphamide followed by docetaxel/trastuzumab (EC-TH) with docetaxel/carboplatin/trastuzumab (TCH) neoadjuvant setting for HER2-positive breast cancer under the single HER2 blockade. METHODS: Patients with stage II-IIIC HER2-positive breast cancer were randomly assigned to either eight cycles of EC-TH every 3 weeks during all chemotherapy cycles, or six cycles of TCH every 3 weeks. The primary endpoint was pathological complete response (pCR) (defined as the absence of invasive tumor cells in breast and axilla, ypT0/is ypN0). RESULTS: From May 2017 to November 2019, 140 patients were randomly assigned, and 135 patients were ultimately found evaluable for the primary endpoint. The pCR was recorded in 25 of 67 patients [37.3%; 95% confidence interval (CI), 25.8-50.0] in the EC-TH group and in 38 of 68 patients (55.9%, 95% CI, 43.3-67.9) in the TCH group (p = 0.032). The most common adverse events (AEs) were neutropenia in 24 of 67 (35.8%) patients in the EC-TH group versus 27 of 68 (39.7%) in the TCH group (p = 0.642), anemia in 33 of 67 (49.3%) patients in the EC-TH group versus 34 of 68 (50.0%) in the TCH group (p = 0.931), and thrombocytopenia in five of 67 (7.5%) patients in the EC-TH group versus 17 of 68 (25.0%) in the TCH group (p = 0.006). CONCLUSION: For patients receiving the single HER2 blockade trastuzumab for HER2-positive breast cancer, TCH regimen might be a preferred neoadjuvant therapy. TRIAL REGISTRATION: This trial was registered with ClinicalTrials.gov identifier: NCT03140553) on 2 May 2017.
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A selectivity switch in a RhII /carbene-triggered cyclopentannulation with catalytic InCl3 is reported for the first time, affording both diastereomers of the fused spiroindolines and an unusual bridged tetracyclic indoline in high yields with excellent selectivities. Mechanistic studies indicate an intramolecular annulation of the indole with an in situ formed aminocyclopropane. The stepwise thermal conversions from the kinetic spiroindoline to the metastable bridged indoline, and then to the thermodynamic spiroindoline, involving a ring-opening rearrangement of a cyclopentane, is crucial for selectivity control.
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Nickel-catalyzed asymmetric annulation of oxygenated phenols and previously challenging 3-aminophenols with ß,γ-unsaturated α-ketoesters is described, leading to rapid access to a variety of oxygenated and 7-aminated chromans in excellent yields with excellent diastereoselectivities and enantioselectivities under mild conditions. This method was readily scaled-up to gram scale and applied for a concise synthesis of two potential anticancer agents 7-aminated 4-arylchromans.
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A facile and efficient method to produce optically pure benzofuroindolines, especially those without 3-substituents that are susceptible to rearomatization, through [3+2] annulation of indoles with quinones is described. The suitable combination of a BOX ligand CuII hydrate complex and freshly activated molecular sieves functions to give controllably dynamic release of water, which enables the success of this reaction. This reaction can be performed on a gram scale with only 0.5â mol % catalyst loading.
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AIM: To construct an inducible artificial microRNA expression vector targeting eIF3g gene and use it to inhibit the expression of eIF3g in K562 cells. METHODS: The microRNA targeting human eIF3g was designed and obtained by PCR. After confirmed by sequencing, the microRNA was cloned into the pRevTRE2 plasmid. The Tet-off plasmids were transfected into K562 cells and selected for the stable tetracycline inducible K562/Tet-off transfectants. The pRevTRE2-eIF3g-miRNA plasmid was then transfected into stable K562/Tet-off transfectants and the expression of eIF3g was detected by Western blot. RESULTS: The microRNA targeting eIF3g was confirmed by sequencing. GFP fluorescence assay showed that the stable transfectants of Tet-off plasmids were under tetracycline control. Western blot results showed that the stable transfectants of pRevTRE2-eIF3g-microRNA inhibited eIF3g expression under the regulation of tetracycline. CONCLUSION: The tetracycline-inducible artificial microRNA expression vector targeting eIF3g gene has been successfully constructed and effectively inhibits eIF3g expression in K562 cells.
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Fator de Iniciação 3 em Eucariotos/genética , Fator de Iniciação 3 em Eucariotos/metabolismo , Vetores Genéticos/genética , MicroRNAs/genética , Regulação Leucêmica da Expressão Gênica/efeitos dos fármacos , Regulação Leucêmica da Expressão Gênica/genética , Humanos , Células K562 , Inibidores da Síntese de Proteínas/farmacologia , Tetraciclina/farmacologiaRESUMO
OBJECTIVE: To report our primary experience with immediate breast reconstruction using laparoscopically harvested omental flap after breast-conserving surgery. The safety, feasibility, and clinical effect are also evaluated. METHODS: From Jun. 2010 to Jan. 2011, 5 cases who underwent immediate breast reconstruction using laparoscopically harvested omental flap after breast-conserving surgery were retrospectively analyzed. The operative duration, postoperative days in hospital, complication and therapeutic effect were reviewed. RESULTS: All the patients were treated successfully without laparotomy. The average operative duration was 310 min, including 60 min for harvesting the omental flap. The median postoperative days in hospital was 8 days (ranged, 5-9 days). One case complained of slight pulled feeling in upper abdomen. No other complication happened. The cosmetic result of reconstructed breasts was satisfactory. CONCLUSIONS: The immediate breast reconstruction using laparoscopically harvested omental flap is safe and feasible with less morbidity in donor sites and good cosmetic effect. It is one of the ideal methods for immediate breast reconstruction.
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Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Omento/transplante , Adulto , Feminino , Humanos , Laparoscopia , Mastectomia Segmentar , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Retrospectivos , Retalhos Cirúrgicos , Resultado do TratamentoRESUMO
To optimize enzymatic hydrolysis of steam-exploded corn stover (SECS), two approaches, response surface methodology (RSM) and utilization of the cellulase from mixed cultures of Trichoderma reesei RUT-C30 and Aspergillus niger NL02, were introduced in this work. The RSM, the first approach, was consisted of Plackett-Burman Design (PBD) and Central Composite Design (CCD). After the optimization of RSM, a model was proposed to predict the optimum value 79.6% confirmed by the experimental result 80.1%. Mixed culture of T. reesei and A. niger was found to be an effective method to enhance cellulolytic enzymes production. Using the cellulase from mixed culture to optimize enzymatic hydrolysis was the second approach. The yield of 85.6% was obtained by the second approach using 25IU/g glucan cellulase. The two approaches were compared and it was found that the second approach was a better one with higher hydrolysis yield and less enzyme dosage.
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Aspergillus niger/enzimologia , Celulase/metabolismo , Vapor , Trichoderma/enzimologia , Zea mays , HidróliseRESUMO
BACKGROUND/AIMS: Preoperative chemotherapy is considered an effective treatment option for patients with gastric cancer. We retrospectively evaluated neoadjuvant chemotherapy with oxaliplatin, leucovorin and 5-flurouracil (OLF) in patients with locally advanced gastric cancer to determine its feasibility, as well as impact on the curative resection rate and patients' survival. METHODOLOGY: A total of 87 patients with locally advanced gastric cancer that underwent preoperative chemotherapy combined with surgery or surgery alone were randomly matched according to the clinical TNM stage. The clinical responses to chemotherapy were assessed. The curative rate, postoperative complications and patients' survival between both groups were compared. RESULTS: The two groups were well matched. Complete or partial response was observed in 51.7% (15/29) of patients in the OLF group, and three (10.3%) of them had complete pathologic response. The curative resection rates were 89.7% in the OLF group and 77.6% in the surgery alone group. The postoperative complications were equal for both groups. The mean survival is 20.6 months in the OLF group vs. 19.9 months in the surgery alone group (p=0.02). CONCLUSIONS: Neoadjuvant chemotherapy using OLF combination is active in gastric cancer and the toxicity level is acceptable. This treatment improves the curative resection rate and patients' survival in locally advanced gastric cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Quimioterapia Adjuvante , Feminino , Fluoruracila/administração & dosagem , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Estudos Retrospectivos , Neoplasias Gástricas/mortalidadeRESUMO
We previously reported that lymphatic mapping using isosulfan blue can be used to identify sentinel nodes (SNs). This study was undertaken to evaluate the feasibility of using the SN technique in treating early gastric cancer and to explore its usefulness for minimal invasive surgery. Twenty-three patients with early gastric cancer who underwent SN biopsy were retrospectively evaluated. Based on SN evaluation, individualized surgery was performed in five patients with T1N0M0 gastric cancer. When pathological examination of frozen sections revealed metastasis in SNs, we performed a standard D2 gastrectomy. Laparoscopic local resection was applied when the SN biopsy was negative. Our results showed that the success rate with SN biopsy in early gastric cancer was 100%, as were the accuracy, sensitivity, and specificity. All five patients with early gastric cancer had SNs negative for metastases both by frozen section and by postoperative pathology. Thus, all these patients underwent laparoscopic local resection without extended lymphadenectomy. We conclude that SN biopsy is a useful tool to individualize the operative procedure, and laparoscopic local resection can be safely performed using SN guidance in selected patients with early gastric cancer.
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Laparoscopia/métodos , Linfonodos/patologia , Biópsia de Linfonodo Sentinela/métodos , Neoplasias Gástricas/secundário , Abdome , Adulto , Endossonografia , Feminino , Seguimentos , Humanos , Metástase Linfática , Masculino , Estadiamento de Neoplasias/métodos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/cirurgiaRESUMO
BACKGROUND AND OBJECTIVES: This study set out to determine the impact of different criteria for radioactive sentinel lymph nodes (SLNs) on sentinel lymph node biopsy (SLNB), and the optimal criteria for radioactive SLNs. METHODS: Eighty-four breast cancer patients with cT1-2N0M0 were studied prospectively. Filtered technetium 99 m sulfur colloid was injected in peritumor parenchyma. Three different definitions of SLNs were adopted in each patient: (1) the lymph node with the highest radioactivity. (2) Any lymph node with an in vivo hot spot-to-background activity ratio of at least 3:1 or an ex vivo SLN-to-non-SLN ratio of at least 10:1. (3) All radioactive hot nodes. RESULTS: With three different definitions, the success rate of sentinel node biopsy were all 96.4%, the sensitivity was 78.9%, 92.1%, 97.4% respectively; false negative rate 21.1%, 7.9%, 2.6% respectively; predicting accuracy 90.1%, 96.3%, 98.8% respectively (P < 0.05). The first, the first two, the first three, and the first four highest radioactive sentinel nodes identified 81.1%, 89.2%, 94.6%, 100% of the positive-SLN patients, respectively. CONCLUSIONS: The different criteria for radioactive SLNs had different impact on the accuracy, sensitivity, and false negative rate, but not on the success rate, during sentinel node biopsy using radioactive sulfur colloid in breast cancer patients. The first four highest radioactive sentinel nodes could accurately predict the status of axillary metastases. J. Surg. Oncol. 2007;95:635-639. (c) 2007 Wiley-Liss, Inc.
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Neoplasias da Mama/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Compostos Radiofarmacêuticos , Biópsia de Linfonodo Sentinela , Coloide de Enxofre Marcado com Tecnécio Tc 99m , Reações Falso-Negativas , Feminino , Humanos , Metástase Linfática , Estudos Prospectivos , Cintilografia , Sensibilidade e EspecificidadeRESUMO
We have encountered an unusual case of gastric carcinoid tumor. Gastroscopic examination of this 32-year-old male patient showed a smooth protrusion at the greater curvature of the gastric body with a central depression, identified by subsequent biopsy as carcinoma. The patient had a normal serum gastrin level and was negative for anti-parietal cell antibody. Histological examination of the resected gastric tissues showed that the tumor was a carcinoid, 0.3 cm x 0.3 cm in size with only one regional lymph node metastasis. We reviewed the pathogenesis, clinical presentation, diagnosis and treatment of gastric carcinoids and raise the possibility of being a lymph vessel-related metastasis even for a minute carcinoid tumor. Sentinel lymph node biopsy is recommended for surgery of minute carcinoid tumors.
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Tumor Carcinoide/patologia , Tumor Carcinoide/cirurgia , Metástase Linfática , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Adulto , Biópsia , Gastroscopia , Humanos , Excisão de Linfonodo , Linfonodos/patologia , Masculino , Estômago/patologia , Resultado do TratamentoRESUMO
OBJECTIVE: To study intra-operative radionuclide lymphatic mapping in sentinel lymph node (SLN) biopsy of breast cancer. METHODS: Forty-two breast cancer (diameter = 5.0 cm) patients with clinically negative axillary node were analyzed. 18.5 MBq/0.5 ml technetium-99m labeled sulfur colloid (labeling yield > 98%, size of colloid granule 100 approximately 200 nm) was injected into the mammary tissue around the tumor or biopsy site at four points. SLN in breast cancer was detected and dissected with the help of lymphoscintigraphy and intra-operative gamma probe. Routine lymph node dissection was performed for all patients. RESULTS: The detection rate was 88.1% in lymphoscintigraphy and 97.6% in intra-operative gamma probe detection for SLN in breast cancer. The sensitivity, accuracy, false negative and specificity of SLN biopsy were 93.3% (14 in 15), 97.6% (40 in 41), 6.7% (1 in 15) and 100% (26 in 26). CONCLUSION: Sentinel lymph node in breast cancer, detected by preoperative lymphoscintigraphy combined with intra-operative gamma probe, is able to predict regional lymph node metastasis. The successful rate of SLN biopsy can be raised by improvement in the quality of nuclear imaging agent, technic of injection and method of measurement.
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Neoplasias da Mama/patologia , Linfonodos/diagnóstico por imagem , Biópsia de Linfonodo Sentinela , Coloide de Enxofre Marcado com Tecnécio Tc 99m , Adulto , Idoso , Neoplasias da Mama/diagnóstico por imagem , Feminino , Humanos , Pessoa de Meia-Idade , CintilografiaRESUMO
OBJECTIVE: To investigate the effects of sodium hyaluronate on the growth and adhesion of colorectal cancer cells. METHODS: Human colorectal cancer cell lines SW620 and Colo205 were treated with sodium hyaluronate (25 -2,500 microg/ml), and cancer cell proliferation was measured by MTT assay in vitro. Flow-cytometric analysis was applied to detect expression of CD44 on SW620 and Colo205 cells. RESULT: In vitro sodium hyaluronate enhanced proliferation of Colo205 cells, but it had no appreciable effect on SW620 growth under the same doses, Meantime, CD44 expression on cancer cells decreased compared with controls. CONCLUSION: In vitro sodium hyaluronate has different effects on growth of different colorectal cancer cell lines, but can inhibit CD44 expression of colorectal cancer cells and influence their ability of adhesion.