RESUMO
BACKGROUND CONTEXT: Elderly patients are less likely to recover from lumbar spine fusion (LSF) as rapidly compared with younger patients. However, there is still a lack of research on the effect of early ambulation on elderly patients undergoing LSF surgery for lumbar degenerative disorders. PURPOSE: To evaluate the safety and benefit of ambulation within 24 hours in elderly patients who underwent LSF. STUDY DESIGN: A retrospective study. PATIENT SAMPLE: Consecutive patients (aged 65 and older) who underwent elective transforaminal lumbar interbody fusion surgery for degenerative disorders from January 2019 to October 2022. OUTCOME MEASURES: Outcome measures included postoperative complications, postoperative drainage (mL), laboratory test data, length of hospital stay [LOS], readmission and reoperation within 3 months. METHODS: Early ambulation patients (ambulation within 24 hours after surgery) were propensity-score matched 1:1 to a delayed ambulation patients (ambulation at a minimum of 48 hours postoperatively) based on age, intraoperative blood loss, and number of fused segments. The incidence of postoperative adverse events (AEs, including rates of complications, readmission, and prolonged LOS) and the average LOS were used to assess the safety and benefit of early ambulation, respectively. Multivariable regression analysis was performed to assess the association between early ambulation and postoperative AEs. The risk factors for delayed ambulation were also determined using multivariable logistic analyses. RESULTS: A total of 998 patients with LSF surgery were reviewed in this study. After excluding 116 patients for various reasons, 882 patients (<24 hours: N=350, 24-48 hours: N=230, and >48 hours: N= 302) were included in the final analysis. After matching, sex, BMI, preoperative comorbidities, laboratory test data and surgery-related variables were comparable between the groups. The incidence of postoperative AEs was significantly lower in the EA group (44.3% vs. 64.0%, p<.001). The average postoperative LOS of the EA group was 2 days shorter than the DA group (6.5 days vs. 8.5 days, p<.001). Patients in the EA group had a significantly lower rate of prolonged LOS compared with the DA group (35.1% vs. 55.3%, p<.001). There was no significant difference in postoperative drainage volumes between the two groups. Multivariable analysis identified older age (odds ratio [OR] 1.07, p<.001), increased intraoperative EBL (OR 1.002, p=.001), and higher international normalization ratio (OR 10.57, p=.032) as significant independent risk factors for delayed ambulation. CONCLUSIONS: Ambulation within 24 hours after LSF surgery is independently associated fewer AEs and shorter hospital stays in elderly patients. Implementing the goal of ambulation within 24 hours after LSF surgery into enhanced recovery after surgery protocols for elderly patients seems appropriate. Older age, increased intraoperative blood loss and worse coagulation function are associated with delayed ambulation.
RESUMO
OBJECTIVE: Compensation characteristics of spinal sagittal malalignment according to pelvic incidence (PI) have yet to be elucidated. This study aimed to investigate the difference in compensatory segments according to PI in elderly patients with degenerative lumbar spinal stenosis (DLSS). METHODS: This retrospective study included 196 patients (143 females, 53 males) suffering from DLSS with an average age of 66.73 years in our department. Sagittal parameters were obtained on the whole spinal lateral radiograph, including T1-T12 slope (T1S-T12S), Cobb angle (CA) of the functional units of the thoracic spine, thoracic kyphosis (TK), lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), PI, the ratio of PT to PI (PT/PI), PI minus LL mismatch (PI-LL), sagittal vertical axis (SVA). Patients were divided into the low and high PI groups according to the median value of PI. With reference to the value of SVA and PI-LL, each PI group was further grouped into the balance subgroup (SVA < 50 mm, PI-LL ≤10°), hidden imbalance subgroup (SVA < 50 mm, PI-LL > 10°), and imbalance subgroup (SVA ≥50 mm). Independent samples t-test/Mann-Whitney U test, one-way ANOVA/Kruskal-Wallis test, and Person correlation analysis were utilized for statistical test. RESULTS: The median value of PI was 47.65°. 96 and 100 patients were assigned to low and high PI groups, respectively. Correlation analysis indicated that the T8-T12 slope and T10-T12 slope were associated with PI-LL in the high and low PI groups, respectively (all, p < 0.01). For segmental lordosis, T8-9 to T11-12 CA and T10-11 to T11-12 CA were associated with PI-LL in the high and low PI groups, respectively (all, p < 0.01). In the high PI cohort, T8-12 CA and PT increased significantly from the balance to imbalance subgroups (both, p < 0.05). In the low PI cohort, T10-12 CA and PT first increased and then decreased from the balance to imbalance subgroups (both, p < 0.05). CONCLUSION: T8-12 was the main compensatory segment of the thoracic spine in patients with high PI, while it was T10-12 in patients with low PI. In addition, the compensation potential of the lower thoracic spine and pelvis in patients with low PI was inferior to those with high PI.
Assuntos
Cifose , Lordose , Estenose Espinal , Masculino , Feminino , Humanos , Idoso , Lordose/diagnóstico por imagem , Estudos Retrospectivos , Vértebras Lombares/diagnóstico por imagem , Estenose Espinal/diagnóstico por imagem , Cifose/diagnóstico por imagemRESUMO
Patients with advanced gastric cancer experience rapid disease progression with limited survival, high mortality, and a lack of surgical options. Thus, radiochemotherapy or a combination of chemotherapeutics with targeted therapy is the mainstay of treatment. In comparison to the treatment of other malignant tumors, in gastric cancer, the development of molecularly targeted drugs has been relatively slow. Currently, there are two major classes of molecularly targeted drug regimens that have achieved a certain efficacy in clinical practice: anti-vascular endothelial growth factor (anti-VEGF) therapy and anti-epidermal growth factor receptor (anti-EGFR) therapy. Trastuzumab has been approved as the standard of care for first-line treatment in advanced human epidermal growth factor receptor 2 (HER2)-positive gastric cancer. Ramucirumab in combination with paclitaxel is the recommended regimen for second-line treatment, and apatinib is recommended as third-line treatment. This review summarizes the current status of targeted therapies in the treatment of gastric cancer and gives a perspective on the future.
Assuntos
Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Trastuzumab/uso terapêutico , Paclitaxel , Terapia de Alvo MolecularRESUMO
BACKGROUND: The aim of the present study was to evaluate the curative effect and safety of thoracic full-endoscopic unilateral laminotomy with bilateral decompression (TE-ULBD) for treating ossification of the ligamentum flavum (OLF) with myelopathy. METHODS: Between January 2015 and December 2018, 23 consecutive patients with symptomatic thoracic OLF were treated with TE-ULBD. Of these, 21 (13 women and 8 men, aged 49-75 years) were included in the study and followed up for a minimum of 1 year. The mean blood loss was 15.48 mL (10-30 mL), operative duration was 78.86 min (55-115 min), and hospitalization was 5.05 days (3-15 days). The Japanese Orthopaedic Association (JOA) was used to evaluate spinal cord function, and the curative effect was defined by the JOA improvement rate. The area of OLF (AOLF), the maximum spinal cord compression (MSCC), and the area of spinal cord (ASC) were used to evaluate OLF clearance and spinal cord decompression status. RESULTS: At the final follow up,the JOA score was 8.33 points (5-11 points), which was a significant improvement from the preoperative 5.33 points (3-9 points, P<0.01). The excellent and good rate was 76.19% (16/21). The average preoperative AOLF and AOLF ratio were 85.27±23.66 mm2 and 57.86%±11.86%, respectively, and the postoperative AOLF and AOLF ratio were 16.27±11.75 mm2 and 8.13%±5.38%, respectively. The MSCC increased from 27.99%±13.51% preoperatively to 48.02%±6.66% postoperatively. The ASC was 42.90±10.60 mm2 preoperatively and 64.54±21.36 mm2 postoperatively. There were statistically significant differences in all parameters preoperatively and postoperatively (P<0.01). One case had postoperative hematoma, and the symptoms gradually eased after 3 weeks of conservative treatment. There were no other complications. No recurrence of OLF was detected during the follow-up period. CONCLUSIONS: TE-ULBD is safe and effective for thoracic OLF with the advantages of reduced trauma and bleeding, and faster recovery.
RESUMO
BACKGROUND: Percutaneous endoscopic lumbar discectomy has been widely used to treat lumbar disc herniation; its advantages are less trauma, faster recovery, lower costs, and higher percentage of patient satisfaction compared with open surgery. Treatment of lumbar spinal stenosis with percutaneous full-endoscopic surgery is still challenging, especially for elderly patients with multiple comorbidities and complex pathologic factors. The aim of this study was to introduce percutaneous full-endoscopic lumbar foraminoplasty and decompression using a visualization reamer in elderly patients with lateral recess and foraminal stenosis and evaluate efficacy and safety. METHODS: This retrospective review comprised 65 consecutive elderly patients (30 men and 35 women) with lateral recess and foraminal stenosis who underwent percutaneous full-endoscopic lumbar foraminoplasty and discectomy from January 2017 to September 2017. Visual analog scale and Oswestry Disability Index were used to evaluate pain relief and neurologic improvement. RESULTS: Mean patient age was 71.58 years (range, 65-89 years). Mean follow-up period was 16.12 months (range, 12-20 months). Mean operative time was 98.59 minutes per level (range, 55-120 minutes). Mean intraoperative perspective frequency was 3.21 times (range, 2-6 times). Mean hospital stay after the procedure was 2.18 days (range, 1-4 days). Back and leg visual analog scale and Oswestry Disability Index scores at all time points in the postoperative period were significantly lower than preoperatively (P < 0.01). At final follow-up, modified MacNab criteria were rated as follows: excellent, 47 patients (72.31%); good, 12 patients (16.92%); fair, 3 patients (4.62%); and poor, 4 patients (6.15%). Therefore, excellent or good results were obtained in 89.23% of patients. CONCLUSIONS: Percutaneous full-endoscopic lumbar foraminoplasty and discectomy using a visualization reamer is an effective and safe treatment for elderly patients with lumbar lateral recess and foraminal stenosis. It improves safety and efficiency of decompression and reduces intraoperative fluoroscopy.
Assuntos
Descompressão Cirúrgica/métodos , Vértebras Lombares/cirurgia , Estenose Espinal/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
RATIONALE: Adult spinal epidermoid cyst (SEC) is a rare tumor. Lumbar laminectomy and tumor removal was a routine surgical procedure for adult spinal epidermoid cyst according to the literature, but postoperative lumbar instability and intractable low back pain may occur. In this study, we presented a brief report of an adult lumbar epidermoid cyst and introduced another surgical approach. PATIENT CONCERNS: This 28-year-old woman has been complaining of the severe right buttock pain and right thigh radiating pain for half a year. She had been diagnosed as sacroiliitis, spinal arthritis, and lumbar disc herniation at 3 different hospitals before coming to our hospital. And she received a variety of conservative treatments, including non-steroidal anti-inflammatory drugs, aspirin, acetaminophen, glucocorticoids, acupuncture, physical therapy, and so on. However, her pain did not diminish at all. Finally, we find a space-occupying lesion in her lumbar magnetic resonance images (MRI). The lesion was slightly low, equal, and uneven equal-low signals on T1WI. T2WI showed slightly higher, equal, and uneven equal-high signals. And a thin-rim enhancement was observed on Gd-DTPA-enhanced MRI. DIAGNOSES: Adult spinal epidermoid cyst. INTERVENTIONS: The patient underwent a surgery of lumbar laminectomy, tumor excision, and spinous process-vertebral plate in situ replantation. OUTCOMES: Postoperative pathology prompted that the tumor was cystoid. The patient's symptoms were completely removed 1 week after surgery. Three-month postoperative MRI confirmed that the spinal epidermoid cyst had been completely removed and three-dimensional CT prompted lumbar lamina in situ. Bony fusion occurred at 6 months after the surgery. LESSONS: Lumbar laminotomy and replantation provides an ideal option to treat adult spinal epidermoid cyst because it can completely remove the cyst and simultaneously reduce the risk of iatrogenic lumbar instability.
Assuntos
Cisto Epidérmico/cirurgia , Laminectomia/métodos , Vértebras Lombares/cirurgia , Reimplante , Doenças da Coluna Vertebral/cirurgia , Adulto , Cisto Epidérmico/diagnóstico por imagem , Feminino , Humanos , Vértebras Lombares/diagnóstico por imagem , Doenças da Coluna Vertebral/diagnóstico por imagemRESUMO
Intervertebral disc degeneration (IDD) is an important factor leading to low back pain, but the underlying mechanisms remain poorly understood. Compared with normal nucleus pulposus (NP) tissues, the expression of circ-GRB10 was downregulated in IDD. Furthermore, overexpression of circ-GRB10 inhibited NP cell apoptosis. circ-GRB10 could sequester miR-328-5p, which could potentially lead to the upregulation of target genes related to cell proliferation via the ErbB pathway. In conclusion, the present study revealed that circ-GRB10/miR-328-5p/ERBB2 signaling pathway is involved in IDD development, suggesting that circ-GRB10 might be a novel therapeutic target for IDD.
Assuntos
Apoptose/genética , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/patologia , Núcleo Pulposo/patologia , RNA/metabolismo , Adulto , Sobrevivência Celular , Feminino , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Anotação de Sequência Molecular , RNA/genética , RNA Circular , Receptor ErbB-2/genética , Receptor ErbB-2/metabolismo , Reprodutibilidade dos Testes , Transdução de Sinais/genéticaRESUMO
OBJECTIVE: Traditional Chinese medicine (TCM) is regarded as an important treatment for gastric cancer patients, especially for those in advanced stage. To evaluate the effects of TCM treatment on gastric cancer patients, the authors performed a retrospective study to report the result of the integrated treatment of TCM with chemotherapy for stage IV non-surgical gastric cancer. METHODS: In this study, 182 patients with stage IV and non-surgical gastric cancer were retrospectively analyzed to evaluate the effects of TCM integrated with chemotherapy. Among the 182 cases, 88 cases received integrated therapy consisting of TCM and chemotherapy, while 94 cases received chemotherapy alone. The overall survival and Karnofsky performance status (KPS) score were measured as the main outcome. RESULTS: The median overall survival of the integrated therapy group and chemotherapy group were 16.9 and 10.5 months, respectively. The 1-, 3- and 5-year survival rates of integrated therapy group vs. chemotherapy group were 70% vs. 32%, 18% vs. 4%, and 11% vs. 0%, respectively. There was a significant difference between the two groups (χ2 = 42.244, P > 0.001). After six-month treatment, KPS scores of the integrated therapy group and the chemotherapy group were 75.00 ± 14.78 and 60.64 ± 21.39, respectively (P > 0.001). The Cox regression analysis showed that TCM treatment is a protective factor for patients' overall survival. CONCLUSION: This study demonstrated that TCM integrated with chemotherapy may prolong overall survival and improve survival rate and life quality of patients with stage IV non-surgical gastric cancer.
Assuntos
Antineoplásicos/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Integrativa , Medicina Tradicional Chinesa , Fitoterapia , Neoplasias Gástricas/tratamento farmacológico , Idoso , Terapia Combinada , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Taxa de SobrevidaRESUMO
Objective To observe the inhibitory effect of Jinlongshe Granule drug-containing serum (JG-DS) on tube formation, migration, and apoptosis of human lymphatic endothelial cells ( HLECs) in vitro. Methods JG-DS was prepared. The 3rd-passage HLECs were divided into the control group (cultured with normal saline containing serum) and the experimental group (cultured with JG-DS). After cultured for 12 h, the tube formation ability was detected by Matrigel assay, and the migration ability was determined by Transwell assay in the two groups. Cell apoptosis rate was detected by flow cytometry and Annexin-V-FITC/Pl staining method. Results The total length of tube was (3 084. 49 ?326. 27) p.m after acted by 10% JG-DS for 12 h, significantly shorter than that of the control group (7 058.93 ?4 567. 39) pm (P <0.01). The migration number of HLECs was (99 ?26), obviously lower than that of the control group (160 ?32; P <0.05). The apoptosis rate of the two groups was not statistically significant (P >0.05). Conclusion JG could inhibit the tube formation and migration of HLECs in vitro, which might be one of mechanisms for inhibiting tumor micro-lymphatics.
Assuntos
Apoptose , Movimento Celular , Medicamentos de Ervas Chinesas , Células Endoteliais , Apoptose/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células , Células Cultivadas , Medicamentos de Ervas Chinesas/farmacologia , Células Endoteliais/efeitos dos fármacos , HumanosRESUMO
Therapy-related acute myeloid leukemia (t-AML) refers to a heterogeneous group of myeloid neoplasms that develop in patients following extensive exposure to either cytotoxic agents or radiation. The development of t-AML has been reported following treatment of cancers ranging from hematological malignancies to solid tumors; however, to our knowledge, t-AML has never been reported following treatment of gastric cancer. In this study, we report the development of t-acute promyelocytic leukemia in a cT4N1M0 gastric cancer patient after an approximate 44 mo latency period following treatment with 4 cycles of oxaliplatin (OXP) (85 mg/m(2) on day 1) plus capecitabine (1250 mg/m(2) orally twice daily on days 1-14) in combination with recombinant human granulocyte-colony stimulating factor treatment. Karyotype analysis of the patient revealed 46,XY,t(15;17)(q22;q21)[15]/46,idem,-9,+add(9)(p22)[2]/46,XY[3], which, according to previous studies, includes some "favorable" genetic abnormalities. The patient was then treated with all-trans retinoic acid (ATRA, 25 mg/m(2)/d) plus arsenic trioxide (ATO, 10 mg/d) and attained complete remission. Our case illuminated the role of certain cytotoxic agents in the induction of t-AML following gastric cancer treatment. We recommend instituting a mandatory additional evaluation for patients undergoing these therapies in the future.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Leucemia Promielocítica Aguda/induzido quimicamente , Neoplasias Gástricas/tratamento farmacológico , Idoso , Biomarcadores Tumorais/genética , Biópsia , Capecitabina/efeitos adversos , Fator Estimulador de Colônias de Granulócitos/efeitos adversos , Humanos , Cariotipagem , Leucemia Promielocítica Aguda/diagnóstico , Leucemia Promielocítica Aguda/tratamento farmacológico , Leucemia Promielocítica Aguda/genética , Masculino , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Valor Preditivo dos Testes , Indução de Remissão , Fatores de Risco , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
Lymphatic metastasis is a major progression route of gastric cancer. Interleukin-8 (IL-8), as an inflammatory cytokine, is induced by Helicobacter pylori infection and is strongly associated with gastric cancer development and metastasis. The blood and lymphatic systems are similar in their function and gene expression profiles. It has been proposed that IL-8 activates angiogenesis. However, the direct role of IL-8 in lymphangiogenesis in gastric cancer remains unclear. We investigated the effect of IL-8 on the growth of human lymphatic endothelial cells (LECs). In addition, protein and mRNA expression of selected lymphangiogenesis markers was assessed in these cells. LECs were co-cultured with gastric cancer SGC7901 cells and exposed to various concentrations of IL-8 (0, 0.2, 0.5, 0.8 and 1.0 ng/ml). The Cell Counting Kit-8 was used to evaluate LEC proliferation (cultured for 1-6 days). Then, protein (immunofluorescence and western blotting) and mRNA [quantitative transcription-polymerase chain reaction (qPCR)] levels were measured in samples obtained from the 24-h cultured cells, for lymphatic vessel endothelial hyaluronic acid receptor-1 (LYVE-1), vascular endothelial growth factor (VEGF)-C, VEGF-D and vascular endothelial growth factor receptor-3 (VEGFR-3). The data presented herein demonstrated that IL-8 promotes the proliferation of LECs and enhances the protein and mRNA expression of LYVE-1. Notably, IL-8 inhibited VEGF-C, VEGF-D and VEGFR-3 protein expression as well as VEGF-D and VEGFR-3 mRNA expression. These findings suggest that IL-8 may be a potent inducer of LECs, although this effect does not appear to involve the VEGF-C/VEGF-D and VEGFR-3 signaling pathway.
Assuntos
Interleucina-8/genética , Neoplasias Gástricas/genética , Fator C de Crescimento do Endotélio Vascular/genética , Fator D de Crescimento do Endotélio Vascular/genética , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genética , Proliferação de Células/genética , Células Endoteliais/metabolismo , Células Endoteliais/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-8/biossíntese , Linfangiogênese/genética , Metástase Linfática/genética , Neovascularização Patológica , RNA Mensageiro/biossíntese , Transdução de Sinais , Neoplasias Gástricas/patologia , Fator C de Crescimento do Endotélio Vascular/biossíntese , Fator D de Crescimento do Endotélio Vascular/biossíntese , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/biossínteseRESUMO
AIM: To determine the underlying mechanisms of action and influence of Xiaotan Sanjie (XTSJ) decoction on gastric cancer stem-like cells (GCSCs). METHODS: The gastric cancer cell line MKN-45 line was selected and sorted by FACS using the cancer stem cell marker CD44; the stemness of these cells was checked in our previous study. In an in vitro study, the expression of Notch-1, Hes1, Vascular endothelial growth factor (VEGF), and Ki-67 in both CD44-positive gastric cancer stem-like cells (GCSCs) and CD44-negative cells was measured by Western blot. The effect of XTSJ serum on cell viability and on the above markers was measured by MTT assay and Western blot, respectively. In an in vivo study, the ability to induce angiogenesis and maintenance of GCSCs in CD44-positive-MKN-45- and CD44-negative-engrafted mice were detected by immunohistochemical staining using markers for CD34 and CD44, respectively. The role of XTSJ decoction in regulating the expression of Notch-1, Hes1, VEGF and Ki-67 was measured by Western blot and real-time polymerase chain reaction. RESULTS: CD44(+) GCSCs showed more cell proliferation and VEGF secretion than CD44-negative cells in vitro, which were accompanied by the high expression of Notch-1 and Hes1 and positively associated with tumor growth (GCSCs vs CD44-negative cells, 2.72 ± 0.25 vs 1.46 ± 0.16, P < 0.05) and microvessel density (MVD) (GCSCs vs CD44-negative cells, 8.15 ± 0.42 vs 3.83 ± 0.49, P < 0.001) in vivo. XTSJ decoction inhibited the viability of both cell types in a dose-dependent manner in vitro. Specifically, a significant difference in the medium- (82.87% ± 6.53%) and high-dose XTSJ groups (77.43% ± 7.34%) was detected at 24 h in the CD44(+) GCSCs group compared with the saline group (95.42% ± 5.76%) and the low-dose XTSJ group (90.74% ± 6.57%) (P < 0.05). However, the efficacy of XTSJ decoction was reduced in the CD44(-) groups; significant differences were only detected in the high-dose XTSJ group at 48 h (78.57% ± 6.94%) and 72 h (72.12% ± 7.68%) when compared with the other CD44- groups (P < 0.05). Notably, these differences were highly consistent with the Notch-1, Hes1, VEGF and Ki-67 expression in these cells. Similarly, in vivo, XTSJ decoction inhibited tumor growth in a dose-dependent manner. A significant difference was observed in the medium- (1.76 ± 0.15) and high-dose XTSJ (1.33 ± 0.081) groups compared with the GCSCs control group (2.72 ± 0.25) and the low-dose XTSJ group (2.51 ± 0.25) (P < 0.05). We also detected a remarkable decrease of MVD in the medium- (7.10 ± 0.60) and high-dose XTSJ (5.99 ± 0.47) groups compared with the GCSC control group (8.15 ± 0.42) and the low-dose XTSJ group (8.14 ± 0.46) (P < 0.05). Additionally, CD44 expression was decreased in these groups [medium- (4.43 ± 0.45) and high-dose XTSJ groups (3.56 ± 0.31) vs the GCSC control (5.96 ± 0.46) and low dose XTSJ groups (5.91 ± 0.38)] (P < 0.05). The significant differences in Notch-1, Hes1, VEGF and Ki-67 expression highly mirrored the results of XTSJ decoction in inhibiting tumor growth, MVD and CD44 expression. CONCLUSION: Notch-1 may play an important role in regulating the proliferation of GCSCs; XTSJ decoction could attenuate tumor angiogenesis, at least partially, by inhibiting Notch-1.
Assuntos
Inibidores da Angiogênese/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Células-Tronco Neoplásicas/efeitos dos fármacos , Neovascularização Patológica , Receptor Notch1/antagonistas & inibidores , Neoplasias Gástricas/irrigação sanguínea , Neoplasias Gástricas/tratamento farmacológico , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Proteínas de Homeodomínio/metabolismo , Humanos , Receptores de Hialuronatos/genética , Receptores de Hialuronatos/metabolismo , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Camundongos Nus , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Ratos Sprague-Dawley , Receptor Notch1/genética , Receptor Notch1/metabolismo , Transdução de Sinais/efeitos dos fármacos , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia , Fatores de Tempo , Fatores de Transcrição HES-1 , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To observe the effects of ethanol extract of Rhizome Pinelliae Preparata on the intracellular pH value of human gastric cancer SGC7901 cells. METHODS: After coculturing SGC7901 cells with ethanol extract of Rhizome Pinelliae Preparata (1, 0.5, 0.25 and 0.125 mg/mL), cell viability was evaluated by chromatometry with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) staining. Intracellular pH value of SGC7901 cells was measured in the monolayer by using the pH-sensitive fluorescent probe 2,7-bis-(2-carboxyethyl)-5-carboxyfluorescein-acetoxymethyl ester. The extracellular pH value of culture medium was measured by a pH211 Calibration Check Microprocessor pH Meter. Half-inhibitory concentration (IC(50)) of ethanol extract culture to SGC7901 cells was decided by the MTT method and expressions of vacuolar-H(+)-ATPase (V-ATPase) and Na(+)/H(+) exchanger isoform 1 (NHE1) mRNAs were examined by the method of fluorescence quantitative-polymerase chain reaction after 72 h of drug treatment. RESULTS: Ethanol extract of Rhizome Pinelliae Preparata at different concentrations significantly inhibited the proliferation of SGC7901 cells, lowered the intracellular pH values and heightened the extracellular pH values. The IC(50) of 72 h culture was 0.5mg/mL and it inhibited the expressions of V-ATPase and NHE1 mRNAs. CONCLUSION: Ethanol extract of Rhizome Pinelliae Preparata can lower down the intracellular pH value of SGC7901 cells. The mechanism may be related to inhibiting the expressions of V-ATPase and NHE1 mRNAs.
Assuntos
Adenocarcinoma/fisiopatologia , Medicamentos de Ervas Chinesas/farmacologia , Extratos Vegetais/farmacologia , Neoplasias Gástricas/fisiopatologia , Proteínas de Transporte de Cátions/metabolismo , Linhagem Celular Tumoral , Humanos , Concentração de Íons de Hidrogênio , Pinellia/química , Rizoma/química , Trocador 1 de Sódio-Hidrogênio , Trocadores de Sódio-Hidrogênio/metabolismo , ATPases Vacuolares Próton-Translocadoras/metabolismoRESUMO
OBJECTIVE: To study the effect of Xiaotan Sanjie Recipe (XTSJD) and its mechanism on vasculogenic mimicry (VM) of human gastric cancer xenografts in nude mice. METHODS: The tumor-bearing mice model was established by subcutaneous inoculating with xenografts of human gastric cancer into the right armpit of 30 BALB/c nude mice. After modeling, the tumor-bearing mice were randomly divided into the normal saline group, the XTSJD group, and the doxycycline hyclate (DH) group, 10 in each. And the mice were administered with corresponding medicine by gastrogavage for 4 weeks. Then all mice were killed by cervical dislocation. The tumor mass were weighed and the tumor inhibition rate calculated. The amount of VM in tumor was counted. Expressions of matrix metalloproteinase (MMP) -2 and MMP-9 were tested using immunohistochemical method. RESULTS: Tumor weight in the XTSJD group and the OH group decreased significantly when compared with the NS group (P<0.01). The amount of VM in the XTSJD group (24.50+/-3.03) and the OH group (14.70+/-1.34) was significantly less than that in the NS group (33.10+/-2.64) (P<0.01). The positive expressions of MMP-2 and MMP-9 in the XTSJD group and the OH group was significantly lower than that in the NS group (P <0.01). CONCLUSION: XTSJD could inhibit the formation of VM in xenografted tumor of nude mice. The mechanism might be correlated with the down-regulation of MMP-2 and MMP-9 expressions.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Gástricas/irrigação sanguínea , Neoplasias Gástricas/metabolismo , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: To observe the mechanism of Xiaotan Sanjie Recipe (XSR) in inhibiting lymphatic metastasis of gastric carcinoma by observing its effects on the expressions of vascular endothelial growth factor-C (VEGF-C) and its receptor VEGFR-3 in nude mice with transplanted human gastric adenocarcinoma cell MKN-45. METHODS: Thirty mice were made into MKN-45 tumor model and randomly divided into three groups treated with saline, 5-Fu, and XSR, respectively. Gene and protein expressions of VEGF-C and VEGFR-3 in the tumor tissue were detected by RT-PCR, and the lymphatic microvessel density (LMVD) in tumor was measured with immunohistochemistry. RESULTS: Compared with the group treated with saline, the mRNA and protein expressions of VEGF-C and VEGFR-3 as well as LMVD level were significantly lower (P < 0.05 or P < 0.01) in the group treated with XSR. There was no significantly statistic difference between the group of XSR and 5-Fu on the indices mentioned above (P > 0.05). CONCLUSION: By down-regulating the mRNA and protein expressions of VEGF-C and VEGFR-3 might be one of possible mechanisms for XSR in preventing and curing the lymphatic metastasis of gastric carcinoma.
Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Neoplasias Gástricas/metabolismo , Fator C de Crescimento do Endotélio Vascular/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
An abnormal microenvironment which is not fit for the living of normal cells is induced and maintained due to rapid growth, abnormal energy metabolism and self-regulation of specific proteins of the tumor cells. At the same time, the abnormal microenvironment is the guarantee of the neoplastic transformation, proliferation, invasion and metastasis of tumor cells. The microenvironment mainly consists of interstitial cells and their components. There are correlations between the physiological role of body fluid and the physiological functions of microenvironment. Phlegm is the product of abnormal body fluid metabolism. So to discuss the correlations of them may contribute to clarifying the material base of phlegm and will further give new insight for integrated traditional Chinese and Western medicine in cancer research.
Assuntos
Medicina Tradicional Chinesa , Neoplasias/patologia , Microambiente Tumoral , Transformação Celular Neoplásica , Humanos , Invasividade NeoplásicaRESUMO
Dissociation of biotin from streptavidin is very difficult due to their high binding affinity. The re-use of streptavidin-modified surfaces is therefore almost impossible, making devices containing them (e.g. surface plasmon resonance (SPR) sensor chips) expensive. This paper describes a new protocol for reversible and site-directed immobilization of proteins with streptavidin affinity tags on the streptavidin-coated SPR biosensor chip (SA chip). Two streptavidin affinity tags, nano-tag and streptavidin-binding peptide (SBP tag), were applied. They both can specifically interact with streptavidin but have weaker binding force compared to the biotin-streptavidin system, thus allowing association and dissociation under controlled conditions. The SA chip surface could be regenerated repeatedly without loss of activity by injection of 50 mM NaOH solution. The fusion construct of a SBP tag and a single-chain antibody to mature bovine prion protein (scFv-Z186-SBP) interacts with the SA chip, resulting in a single-chain-antibody-modified surface. The chip showed kinetic response to the prion antigen with equilibrium dissociation constant K (D) approximately equal to 4.01 x 10(-7). All results indicated that the capture activity of the SA chip has no irreversible loss after repeated immobilization and regeneration cycles. The method should be of great benefit to various biosensors, biochips and immunoassay applications based on the streptavidin capture surface.
Assuntos
Técnicas Biossensoriais/métodos , Região Variável de Imunoglobulina/química , Príons/química , Análise Serial de Proteínas/métodos , Estreptavidina/química , Ressonância de Plasmônio de Superfície/métodos , Animais , Bovinos , Peptídeos/química , Sensibilidade e Especificidade , Propriedades de Superfície , Fatores de TempoRESUMO
Discovering molecular heterogeneities in phenotypically defined disease is of critical importance both for understanding pathogenic mechanisms of complex diseases and for finding efficient treatments. Recently, it has been recognized that cellular phenotypes are determined by the concerted actions of many functionally related genes in modular fashions. The underlying modular mechanisms should help the understanding of hidden genetic heterogeneities of complex diseases. We defined a putative disease module to be the functional gene groups in terms of both biological process and cellular localization, which are significantly enriched with genes highly variably expressed across the disease samples. As a validation, we used two large cancer datasets to evaluate the ability of the modules for correctly partitioning samples. Then, we sought the subtypes of complex diffuse large B-cell lymphoma (DLBCL) using a public dataset. Finally, the clinical significance of the identified subtypes was verified by survival analysis. In two validation datasets, we achieved highly accurate partitions that best fit the clinical cancer phenotypes. Then, for the notoriously heterogeneous DLBCL, we demonstrated that two partitioned subtypes using an identified module ("cellular response to stress") had very different 5-year overall rates (65% vs. 14%) and were highly significantly (P < 0.007) correlated with the clinical survival rate. Finally, we built a multivariate Cox proportional-hazard prediction model that included 4 genes as risk predictors for survival over DLBCL. The proposed modular approach is a promising computational strategy for peeling off genetic heterogeneities and understanding the modular mechanisms of human diseases such as cancers.