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Patients with human epidermal growth factor receptor 2 (HER2) overexpression or amplification in gastric and esophagogastic adenocarcinoma can significantly benefit from anti-HER2 therapies. Presently, various humanized monoclonal antibodies such as trastuzumab and pertuzumab, alongside diverse anti-HER2 antibody drug conjugates (trastuzumab emtansine, disitamab vedotin, trastuzumab deruxtecan, ARX788), and tyrosine kinase inhibitors (lapatinib, afatinib, pyrotinib), are employed either as monotherapy or in combination settings for advanced gastric and esophagogastic adenocarcinoma. These therapeutic modalities have demonstrated promising clinical efficacy in clinical trials, thereby ameliorating patients' prognosis and enhancing life quality. Further exploration on the efficacy and safety of novel HER2-targeted agents and combined therapeutic regimens in clinical practice holds the promise of furnishing more efficacious strategies for treating HER2-positive advanced gastric and esophagogastic adenocarcinoma.
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ObjectiveTo observe the clinical efficacy and safety of treating mediate-risk pure ground glass pulmonary nodules (pGGNs) based on the state theory. MethodsA prospective clinical randomized controlled trial was used. Totally 141 cases of mediate-risk pGGNs were divided into treatment group (92 cases) and control group (49 cases) according to the random table method. The treatment group was given the basic Sanjie Formula (基础散结方) orally with modification according to the identification of traditional Chinese medicine (TCM) state, 1 dose per day, 3 months as a course of treatment.Three months after the treatment patients were checked by CT. Patients who were clinically judged as cure, moderate to low risk, and turned to surgical resection do not carry out a second course of treatment,and the rest of the patients continued to complete the second courses. Patients in the control group did not receive any treatment and were only followed up periodically. Patients in both groups received a CT review 3 months and 6 months after enrolled. Comprehensive curative effect was evaluated according to the reduction rate of the area of pulmonary nodules shown in chest CT, to further explore the clinical effective difference for patients at different TCM state; the risk of malignancy index (Mayo score) was calculated by Mayo model at enrollment and 3 months and 6 months after enrolled. Adverse events were monitored continuously during the study. ResultsDuring the follow-up, 8 cases in the treatment group and 7 cases in the control group were lost. A total of 126 cases completed the whole process, including 84 cases in the treatment group and 42 cases in the control group. The total effective rates at 3 months and 6 months of the treatment group were 46.15% (30/65) and 45.71% (32/70) in the treatment group, while the total effective rates at 3 months and 6 months in the control group were 12.5% (4/32) and 10.00% (4/40). Compared with the control group, the comprehensive curative effect of 3 months and 6 months of enrollment in treatment group was significantly better than that in corresponding control group (P<0.01). The pulmonary nodule area and Mayo score in the treatment group decreased after 3 and 6 months of enrollment (P<0.01). In contrast, there was no statistically significant difference in nodule area between pre- and post-enrollment time points in the control group (P>0.05), and probability of Mayo risk increased in the control group after 6 months of enrollment compared to pre-enrollment (P<0.05). Among the 84 patients in the treatment group, there were 15 cases of qi deficiency state, 7 cases of yin deficiency state, 5 cases of yang deficiency state, 20 cases of qi depression state, 32 cases of damp-heat state, and 5 cases of harmonious state; the difference in the distribution of the total clinical effective rate of the patients with different TCM states after treatment was statistically significant (P<0.05), and the total effective rate of two-by-two comparison of qi depression state was higher (13/20,65.00%) than that of the total effective rate of damp-heat state (8/32,25.00%, P<0.00833). There were no significant changes in blood routine, urine routine, liver function and kidney function in both groups, and no adverse events occurred. ConclusionTreating mediate-risk pGGNs based on the state theory can effectively reduce the area of pulmonary nodules and inhibit the growth of malignant risk of pulmonary nodules.
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RhoE, a small G protein, is constitutively GTP bound within the cell and can regulate actin cytoskeleton reorganization, leading to the appearance of aggregates of actin filaments. Although emerging evidence suggests that RhoE is causally involved in cancer formation and progression, little is known about its significance in solid cancer, including lung cancer. In the present study, the expression of RhoE was analyzed using Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR), real-time RT-PCR, immunohistochemistry and western blot in 30 patients with Non-small Cell Lung Cancer (NSCLC). Then the correlation of RhoE overexpression with clinical parameters was evaluated. Furthermore, the possible reasons contributing to the RhoE expression were examined by real-time genomic PCR and mutation analysis on DNA sequence and cDNA sequence. Our results revealed that RhoE expression was dramatically increased in lung cancer tissues compared with adjacent nontumoral lung tissues (p <0.01). Immunohistochemistry showed a strong cytoplasmic staining in cancer cells compared with positive membrane staining in adjacent nontumoral proliferative alveolar epitheliums. Moreover, the overexpression of RhoE was significantly associated with the patients' smoking history (p <0.05). 72% tumor tissues displayed DNA copy number changes based on the DNA levels in the matched adjacent nontumoral lung tissues and this copy number changes correlated significantly with RhoE expression and smoking history (p <0.05). Three polymorphisms were identified but no correlation was found with the clinicopathological features. To our knowledge, this is the first report demonstrating that overexpression of RhoE correlated with smoking and DNA copy number changes, suggesting that RhoE may serve as a molecular marker to identify high-risk individuals and assist in the identification of additional pathways of carcinogenesis.
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Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , Fumar/genética , Proteínas de Unión al GTP rho/genética , Regiones no Traducidas 3'/genética , Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/química , ADN de Neoplasias/análisis , Amplificación de Genes , Dosificación de Gen , Humanos , Inmunohistoquímica , Neoplasias Pulmonares/química , Polimorfismo de Nucleótido Simple , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Regulación hacia Arriba , Proteínas de Unión al GTP rho/análisisRESUMEN
Objective:To study the expression and significance of long noncoding RNA (lncRNA) LINC00657 in diffuse-type adenocarcinoma of esophagogastric junction (AEG).Methods:RT-PCR was used to determine the expression of LINC00657 in AEG tissues and AEG patient-derived tumor cells (PDCs). The expression of E-cadherin in AEG tissues and PDCs was detected. The Kaplan-Meier method was used to evaluate the correlation of LINC00657 expression with the overall survival (OS) of patients.Results:LINC00657 was highly expressed in AEG tissues [(1.41±0.12) vs. (0.61±0.11), t=276.038, P<0.01] and PDCs, while E-cadherin was significantly down-regulated. The expression of LINC00657 was retated to tumor diamer, invassion depth, lymph node metastasis, TNM staging (all P<0.05) In Kaplan-Meier analysis, high levels of LINC00657 were associated with poor prognosis for patients with diffuse-type AEG. In addition, a significant inverse relationship was observed between LINC00657 and E-cadherin expression ( r=-0.529, P<0.001). Conclusions:Elevated expression of LINC00657 in diffuse-type AEG tissues is associated with poor prognosis and may confer a malignant phenotype upon tumor cells.
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Objective: To evaluate and compare the clinical value of early enteral nutrition (EEN) and total parenteral nutrition (TPN) af-ter esophageal cancer surgery. Methods: We retrospectively analyzed 237 patients who underwent esophageal cancer surgery at Bei-jing Shijitan Hospital from March 2011 to March 2019. They were assigned into two groups based on the postoperative nutritional sup-port used: EEN (136 cases) and TPN (101 cases). Nutritional status, liver function, recovery of gastrointestinal function, days of hospital-ization, and postoperative complications were compared between the two groups after propensity score matching. Results: Using 1 :1 nearest neighbor matching, we successfully matched 91 pairs of patients. The prealbumin (PA) level was significantly higher in the EEN group than in the TPN group 7 days after surgery (P<0.05); however, there was no significant difference in albumin (ALB) level before surgery, 3 or 7 days after surgery. Additionally, the levels of ALT and AST in the EEN group were significantly lower than those in the TPN group 3 and 7 days after surgery (P<0.05). The incidence of acid reflux, vomiting, and diarrhea in the EEN group was higher than that in the TPN group, while the incidence of pulmonary edema and pulmonary infection was lower in the EEN group than in the TPN group (P<0.05). Conclusions: Compared with TPN, EEN is associated with a high incidence of acid reflux, vomiting, and diarrhea after esophageal cancer surgery, but it has a lower impact on liver function. EEN can promote the recovery of intestinal function, improve nutritional indicators, and shorten hospitalization time.
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Objective To investigate the effect of long non-coding RNA HOX transcript antisense RNA ( lncRNA HOTAIR ) on the cell proliferation, radiosensitivity and apoptosis of the rectal adenocarcinoma cell lines SW480 and HCT116 in vitro. Methods The expression levels of lncRNA HOTAIR in the rectal adenocarcinoma cell lines ( SW480 and HCT116 ) were assessed by real-time quantitative PCR (RT-qPCR).Silencing of HOTAIR by RNA interference was performed to explore its roles in cell proliferation,radiosensitivity and apoptosis. After treatment with irradiation at a gradient dose,the cell viability was measured and the rate of cell apoptosis was tested. Results Compared with the human rectal epithelial cell lines,the expression of lncRNA HOTAIR was significantly higher in the rectal adenocarcinoma cell lines. The colonic assay demonstrated that the sensitizing enhancement ratios ( SERs) were 1. 58 and 1. 33 for the cells transfected with HOTAIR siRNA in SW480 and HCT116 cell line compared with the control isRNA transfection group. In vitro silencing of lncRNA HOTAIR could enhance the apotosis rate and radiosensitivity of the rectal adenocarcinoma cell line SW480. Conclusion The expression level of lncRNA HOTAIR is correlated with the cellular radiosensitivity, which is probably a parameter for predicting the radiosensitivity of rectal adenocarcinoma cells. Radiotherapy combined with HOTAIR-siRNA can significantly inhibit the cell proliferation,induce cell apoptosis and enhance the radiosensitivity.
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Objective To evaluate the changes of CEA,CA19-9,CA72-4 of patients with advanced adenocarcinoma of the esophagogastric junction (AEGJ) who received ultra-early precise hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) with paclitaxel (PTX) after radical surgery.Methods From Jul 2014 to Dec 2015 postoperative advanced AEGJ patients were divided to receive ultraearly precise HIPEC (87 cases,HIPEC group) and conventional therapy group (85 cases) in early stage after radical surgery.Serum levels of CEA,CA19-9 and CA72-4 were examined on preoperative day 1 and postoperative day 9.Results On post-op day 9,the level of CEA,CA19-9 and CA72-4 was (2.8 ± 1.3)ng/ml,(22 ±8)IU/ml,(4.1 ± 1.9)IU/ml in HIPEC group,while that was (3.4 ± 1.2)ng/ml,(25 ±11) IU/ml,(4.8 ± 2.1) IU/ml in control group respectively (t =2.453,P =0.015;t =2.241,P =0.026;t =2.154,P =0.033).Conclusion Ultra-early PTX-based HIPEC with advanced AEGJ after radical surgery lowers serum tumor makers of CEA,CA19-9,CA72-4,reducing body's tumor burden.
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Objective To evaluate T lymphocyte changes in esophagogastric junction adenocarcinoma (AEGJ) patients receiving early hyperthermic intraperitoneal perfusion chemotherapy (HIPEC) after radical resection.Methods 98 AEGJ cases were randomized into postoperative early paclitaxel HIPEC group (50 cases) and surgery only group (48 cases).The changes in TLC,CD3 +,CD4 +,CD8 + and CD4 + CD25 + were examined by using flow cytometry on the preoperaive d1,and on the postoperative d 9.Results There were significant differences in cellular ratios of TLC,CD3 +,CD4 +,CD8 + and CD4 + CD25 + between the two groups on postoperative d 9 [(1.85 ± 0.36) × 109/L,(1.28 ± 0.28) ×109/L,t=8.727,P<0.001;76% ±6%,65% ±6%,t =8.680,P<0.001;57% ±8%,41% ± 7%,t =10.246,P <0.001:20% ±7%,25% ±6%,t =4.037,P <0.001;4.2% ±1.8%;6.7% ± 2.0%,t =6.548,P < 0.001].Conclusion Postoperative early HIPEC using paclitaxel improves the celluar immune activity of T cell subsets in advanced AEGJ patients.
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<p><b>OBJECTIVE</b>To evaluate the patterns of recurrence and the related factors in patients with pT3N0M0 thoracic esophageal squamous cell carcinoma (ESCC) after two-field esophagectomy.</p><p><b>METHODS</b>From Jan 2008 to Dec 2009, 208 patients with stage pT3N0M0(2002, UICC) thoracic ESCC were treated with two-field esophagectomy in our hospital. There were 138 males and 70 females, and the median age was 60 years old (range 33-78). There were 33 patients in the upper-, 134 in the middle-, and 41 in the lower-thoracic esophagus, with a median length of lesion of 5 cm. There were 32 patients with no-, 78 with mild- and 98 patients with severe adhesions at surgery. The median number of dissected lymph nodes was 9 (range 1-27). 98 patients were treated with surgery alone and 110 with postoperative adjuvant chemotherapy. The statistical analysis was conducted using SPSS 13.0 software.</p><p><b>RESULTS</b>The follow-up was ended on July 2013. In the total group of 208 patients, the total recurrence rate was 41.8% (87/208). Among them, 52 patients had locoregional recurrence (LR), 15 had distant metastasis (DM) and 20 patients had both local recurrence and distant metastasis. 40.2% (35/87) of all recurrences were found within one year after operation, 67.8% (59/87) within 2 years, 86.2% (75/87) within 3 years, and 100% (87/87) within 4 years. The 1-, 3-, and 5-year progression-free survival (PFS) rate was 83.0%, 62.8% and 56.3%, respectively. The overall locoregional recurrence rate was 34.6% (72/208), among them, 9 cases had recurrence in the cervix (all were supraclavicular lymph node metastasis), 66 cases in the mediastinum and 4 cases had para-aortic lymph node metastasis. 83.3% (60/72) of the locoregional recurrence was located in the carinal region or upper area. The 1-, 3-, 5-year locoregional recurrence rate was 15.6%, 32.2%, and 36.8%, respectively, and the median time of recurrence was 15.5 months. The overall distant metastasis (DM) rate was 16.8% (35/208). The 1-, 3-, and 5-year DM rate was 4.4%, 15.3%, and 20.1%, respectively, and the median time of DM was 24 months. The most common site of DM was the lung and bone. The univariate analysis showed that age and tumor site were associated with PFS, tumor site and small lymph node in the mediastinum (diamter <1 cm) before surgery were related with LR (P<0.05 for all), and tumor site, histological differentiation and LR were related with distant metastasis after surgery (P<0.05). Multivariate analysis showed that the tumor site was an independent prognostic factor affecting the progression-free survival and locoregional recurrence (P<0.05), and histological differentiation and LR were independent factors associated with distant metastasis (P<0.05 for all).</p><p><b>CONCLUSIONS</b>The recurrence rate is very high in patients with pT3N0M0 thoracic ESCC after surgery, and most of them occur within 3 years after operation. Locoregional recurrence occurs more frequently and shortly than distant metastasis, and most of LR is located in the carinal region or upper-mediastinum. LR rate in upper-thoracic ESCC is very high, therefore, postoperative radiotherapy (PORT) is strongly suggested. LR rate in middle thoracic ESCC is also rather high and PORT is suggested. LR occur much less in the lower-thoracic ESCC, thus, PORT is not suggested routinely. Patients with poorly differentiated ESCC and LR have a high rate of distant metastasis.</p>
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Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Carcinoma de Células Escamosas , Quimioterapia , Patología , Cirugía General , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Neoplasias Esofágicas , Quimioterapia , Patología , Cirugía General , Esofagectomía , Métodos , Escisión del Ganglio Linfático , Ganglios Linfáticos , Metástasis Linfática , Mediastino , Análisis Multivariante , Cuello , Recurrencia Local de Neoplasia , Patología , Estadificación de Neoplasias , Periodo PosoperatorioRESUMEN
Objective To explore the inhibitory effects of sulfated oligosaccharides PI-88 on the heparanase protein expression of human esophageal squamous cancer cell (ESCC) line TE-13, and to explore the effects of growth, angiogenesis and heparanase protein expression on ESCC xenografts of nude mice. Methods TE-13 cells were cultured and divided into three groups:group A (control group), group B (15 mg/L PI-88) and group C (30 mg/L PI-88). Heparanase protein expression of TE-13 cells was measured by Western blot assay after being cultured for 36 h. The ESCC suspension was injected subcutaneously in 10 BALB/c/nu mice to build up ESCC xenograft model. The model mice were divided randomly into observation group and control group (5 mice per group). The mice in observation group received 40 mg/(kg·d) PI-88. The mice in control group only received the same volume of saline at the same time. Both PI-88 and saline were daily administrated for 14 days. Every 2 days,the volume of xeongrafts were measured and the mice were executed at the 14th day. CD34 immunohistochemical staining was used to detect the micro vessel density (MVD) of xenografts. Western blot assay and immunohistochemical staining were used to detect the heparanase protein expression of xenografts. Results The heparanase protein expressions of TE-13 cells were significantly decreased in group B and group C than those of group A (P<0.001), with a kind of PI-88 dose-dependent manner. The volume, MVD and heparanase protein expression of xenografts were significantly lower in observation group than those of control group (P<0.05). Conclusion The heparanase protein expression in TE-13 cells can be inhibited by PI-88 in vitro and vivo. Furthermore, the growth and angiogenesis of ESCC xenografts were also inhibited by PI-88.
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<p><b>OBJECTIVE</b>To investigate the predictive value of P53, Ki-67, HER2 protein detection in neoadjuvant chemotherapy for adenocarcinoma of gastroesophageal junction (AGEJ).</p><p><b>METHODS</b>Preoperative biopsy specimens and clinical data of 72 patients of locally advanced Siewert II AGEJ between June 2010 and December 2013 were reviewed. All the patients received SOX scheme neoadjuvant chemotherapy, and were divided into effective group (complete response plus partial response) and ineffective group (stable disease plus progressive disease). Expressions of above 3 proteins were detected by immunohistochemistry in all the patients before neoadjuvant chemotherapy. The relationship between various proteins and efficacy of chemotherapy was analyzed by univariate and logistic multivariate regression analyses.</p><p><b>RESULTS</b>All the 72 patients successfully completed 2 cycles of SOX neoadjuvant chemotherapy, among them, 5 cases (6.9%) with complete response, 30 cases (41.7%) with partial response, 31 cases (43.1%) with stable disease, 6 cases (8.3%) with progressive disease, including 35 cases in effective group and 37 cases in ineffective group. Compared with ineffective group, the positive expression rate of P53 was significantly reduced (25.0% vs. 45.9%, P=0.020), and that of Ki-67 significantly increased (77.1% vs. 43.2%, P=0.003), however, there was no significant difference in the expression rate of HER2 between the two groups (P>0.05). Multivariate analysis showed that Ki-67 was the independent predictive factor for the efficacy of neoadjuvant chemotherapy (P=0.015). Spearman rank correlation showed that Ki-67 expression was positively correlated with HER2 expression (r=0.259, P=0.028), but P53 expression was not correlated with Ki-67 or HER2 (r=0.140, 0.042, P=0.240, 0.725, respectively).</p><p><b>CONCLUSIONS</b>SOX neoadjuvant chemotherapy is safe and effective for AGEJ, especially for patients with depressed expression of P53 and elevated expression of Ki-67, which both may be used as reference for the prediction of chemotherapy efficacy. There is no correlation between P53 and Ki67 proteins, so combined detection may improve the predictive value.</p>
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Humanos , Adenocarcinoma , Diagnóstico , Quimioterapia , Neoplasias Esofágicas , Diagnóstico , Quimioterapia , Unión Esofagogástrica , Patología , Inmunohistoquímica , Antígeno Ki-67 , Metabolismo , Terapia Neoadyuvante , Receptor ErbB-2 , Metabolismo , Inducción de Remisión , Proteína p53 Supresora de Tumor , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To investigate the effect of NF-κB activation on radiation response of esophageal carcinoma.</p><p><b>METHODS</b>The expression of NF-κB was detected in pretreatment and posttreatment specimens of patients with ESCC by immunohistochemistry. Electrophoretic mobility shift assay (EMSA) and Western blot were used to detect the activation of NF-κB in esophageal cancer cell line KYSE150 cells. SN50, a specific NF-κB inhibitor, was applied to inhibit the activation of NF-κB. Clone formation test was used to detect the radiosensitivity of esophageal cancer cells.</p><p><b>RESULTS</b>The median survival time of patients with activated and inactivated NF-κB in the pretreatment specimens were 16 and 19 months, respectively, with a non-significant difference between the two groups (P > 0.05). As to the patients with activated and inactivated NF-κB in posttreatment specimens, the median survival times were 13 and 35 months, respectively, with a significant difference (P < 0.01) between them. Western blot showed that the cytoplasmic expression of NF-κB was reduced with increasing radiation dose at 1.5 and 3 hours after radiation treatment. However, the expression of NF-κB in the cell nuclei was increased under the same condition, showing a trend of increased nucleus/cytoplasm ratio. The clone number in SN50 group was 96.66, 64.66, 76.66 and 10.00 under 0, 2, 4 and 12 Gy irradiation, which demonstrated a significant difference compared with the control groups (P < 0.001).</p><p><b>CONCLUSIONS</b>Our results show that activation of NF-κB is induced by radiotherapy. Activation of NF-κB reduces the outcome of radiation treatment of esophageal cancer patients.</p>
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Humanos , Western Blotting , Línea Celular Tumoral , Núcleo Celular , Neoplasias Esofágicas , Metabolismo , Radioterapia , Inmunohistoquímica , FN-kappa B , Metabolismo , Tolerancia a Radiación , Transducción de SeñalRESUMEN
Objective To compare the clinical results of surgical and conservative treatment of acute patellar dislocations.Methods Retrospective analyzed the clinical data of 35 patients with acute patellar dislocations from June 2004 to October 2009,and divided the patients into 2 groups.One group with 18 patients underwent surgical treatments,and the other group with 17 patients underwent conservative treatments,record the number of relapses cases of both the two groups.A radiographic examination was performed in the evaluation of the patients,and the Kujala questionnaire was applied with the intention of analyzing the improvement of pain and quality of life.Results All patients were followed up for more than 12 months.(1) The conservative treatment group exhibited a higher number of recurrent dislocations (7 patients) (41.2%) than the surgical treatment group,which did not have any relapses (x2 =9.265,P =0.002).(2) The patellar tilt returned to normal in the surgical group,while 8 patients returned to normal in the conservative group,with statistical difference between groups (x2 =10.980,P =0.001).And the lateral shift ratio returned to normal in the surgical group,while 6 patients returned to normal in the conservative group,with statistical difference between groups(x2 =7.667,P =0.006).(3)The surgical treatment group obtained a significantly better mean score on the Kujala test than preoperative ((90 ± 5) vs.(58 ± 6),t =16.465,P < 0.01) ; The conservative treatment group,compared with the preoperative,is not improved obviously ((72 ± 6) vs.(62 ± 8),t =0.943,P > 0.05) ;Postoperative group comparison,surgical group was higher than that in conservative group,there was significant difference between two groups (t =12.256,P < 0.01).Conclusion For acute patellar dislocation,surgical treatment can significantly restore patellar stability,improve the function of knee joint.