[Organ preservation and watch-and-wait strategy in esophageal cancer: a promising future].

The traditional treatment modalities for esophageal cancer include surgery, chemotherapy, and radiotherapy, each presenting its own limitations. With advancements in endoscopic techniques and the integration of immunotherapy, the feasibility and safety of organ preservation have significantly improved, offering patients improved survival and quality of life. The selection of patients suitable for organ preservation treatment demands ongoing exploration. Those selected for this approach require rigorous monitoring, with surgical intervention as a salvation for tumor progression or metastasis, though the timing of surgery remains a topic of debate. Organ preservation and watch-and-wait strategy may provide a more conservative treatment option, aiming to maximize quality of life.

[Prevention and treatment of postoperative complications of esophageal cancer].

Surgery is the primary treatment for esophageal cancer, but the postoperative complication rate remains high. Therefore, it is important to prevent and manage postoperative complications to improve prognosis. Common perioperative complications of esophageal cancer include anastomotic leakage, gastrointestinal tracheal fistula, chylothorax, and recurrent laryngeal nerve injury. Respiratory and circulatory system complications, such as pulmonary infection, are also quite common. These surgery-related complications are independent risk factors for cardiopulmonary complications. Complications, such as long-term anastomotic stenosis, gastroesophageal reflux, and malnutrition are also common after esophageal cancer surgery. By effectively reducing postoperative complications, the morbidity and mortality of patients can be reduced, and their quality of life can be improved.

Unintrusive multi-cancer detection by circulating cell-free DNA methylation sequencing (THUNDER): development and independent validation studies.

BACKGROUND: Early detection of cancer offers the opportunity to identify candidates when curative treatments are achievable. The THUNDER study (THe UNintrusive Detection of EaRly-stage cancers, NCT04820868) aimed to evaluate the performance of enhanced linear-splinter amplification sequencing, a previously described cell-free DNA (cfDNA) methylation-based technology, in the early detection and localization of six types of cancers in the colorectum, esophagus, liver, lung, ovary, and pancreas. PATIENTS AND METHODS: A customized panel of 161 984 CpG sites was constructed and validated by public and in-house (cancer: n = 249; non-cancer: n = 288) methylome data, respectively. The cfDNA samples from 1693 participants (cancer: n = 735; non-cancer: n = 958) were retrospectively collected to train and validate two multi-cancer detection blood test (MCDBT-1/2) models for different clinical scenarios. The models were validated on a prospective and independent cohort of age-matched 1010 participants (cancer: n = 505; non-cancer: n = 505). Simulation using the cancer incidence in China was applied to infer stage shift and survival benefits to demonstrate the potential utility of the models in the real world. RESULTS: MCDBT-1 yielded a sensitivity of 69.1% (64.8%-73.3%), a specificity of 98.9% (97.6%-99.7%), and tissue origin accuracy of 83.2% (78.7%-87.1%) in the independent validation set. For early-stage (I-III) patients, the sensitivity of MCDBT-1 was 59.8% (54.4%-65.0%). In the real-world simulation, MCDBT-1 achieved a sensitivity of 70.6% in detecting the six cancers, thus decreasing late-stage incidence by 38.7%-46.4%, and increasing 5-year survival rate by 33.1%-40.4%, respectively. In parallel, MCDBT-2 was generated at a slightly low specificity of 95.1% (92.8%-96.9%) but a higher sensitivity of 75.1% (71.9%-79.8%) than MCDBT-1 for populations at relatively high risk of cancers, and also had ideal performance. CONCLUSION: In this large-scale clinical validation study, MCDBT-1/2 models showed high sensitivity, specificity, and accuracy of predicted origin in detecting six types of cancers.

Neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy followed by minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma: a prospective multicenter randomized clinical trial.

BACKGROUND: Neoadjuvant therapy is recommended for locally advanced esophageal cancer, but the optimal strategy remains unclear. We aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) versus neoadjuvant chemotherapy (nCT) followed by minimally invasive esophagectomy (MIE) for locally advanced esophageal squamous cell carcinoma (ESCC). PATIENTS AND METHODS: Eligible patients staged as cT3-4aN0-1M0 ESCC were randomly assigned (1 : 1) to the nCRT or nCT group stratified by age, cN stage, and centers. The chemotherapy, based on paclitaxel and cisplatin, was administered to both groups, while concurrent radiotherapy was added for the nCRT group; then MIE was carried out. The primary endpoint was 3-year overall survival. This study is registered with ClinicalTrials.gov (NCT03001596). RESULTS: A total of 264 patients were eligible for the intention-to-treat analysis. By 30 November 2021, 121 deaths had occurred. The median follow-up was 43.9 months (interquartile range 36.6-49.3 months). The overall survival in the intention-to-treat population was comparable between the nCRT and nCT strategies [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.58-1.18; P = 0.28], with a 3-year survival rate of 64.1% (95% CI 56.4% to 72.9%) versus 54.9% (95% CI 47.0% to 64.2%), respectively. There were also no differences in progression-free survival (HR 0.83, 95% CI 0.59-1.16; P = 0.27) and recurrence-free survival (HR 1.07, 95% CI 0.71-1.60; P = 0.75), although the pathological complete response in the nCRT group (31/112, 27.7%) was significantly higher than that in the nCT group (3/104, 2.9%; P < 0.001). Besides, a trend of lower risk of recurrence was observed in the nCRT group (P = 0.063), while the recurrence pattern was similar (P = 0.802). CONCLUSIONS: NCRT followed by MIE was not associated with significantly better overall survival than nCT among patients with cT3-4aN0-1M0 ESCC. The results underscore the pending issue of the best strategy of neoadjuvant therapy for locally advanced bulky ESCC.

[Advantages and disadvantages of transthoracic approach for adenocarcinoma of the esophagogastric junction].

Adenocarcinoma of the esophaogastric junction (AEG) has anatomical characteristics of spanning two organs and anatomical sites. Thoracic surgery and gastrointestinal surgery aim at the safe resection margin of esophagus, the scope of lower mediastinal lymph node dissection and whether transthoracic surgery will increase complications. However, there are great differences and controversies in the surgical approach, surgical method, lymph node dissection and extent of resection of AEG. For Siewert II AEG via abdominal mediastinal approach, due to the limitation of exposure and the difficulty of operation, it is difficult to acquire a satisfactory proximal resection margin, and very difficult to dissect the inferior mediastinal lymph nodes. The transthoracic approach can provide adequate exposure, reduce the difficulty of operation, obtain satisfactory resection margin of esophagus and allow lower mediastinal lymph node dissection, which may bring better prognosis. Although transthoracic approach may increase the incidence of pulmonary infection, the standard development of thoracoscopic technology will overcome the disadvantage of transthoracic approach for Siewert II AEG.

[Analysis of the efficacy and prognostic factors of 1 637 esophageal cancer patients treated with intensity-modulated radiotherapy].

Objective: To summarize survival outcomes and prognostic factors in esophageal cancer (EC) patients treated with intensity-modulated radiotherapy (IMRT). Methods: A retrospective analysis was performed on the clinical and follow-up data of 1 637 patients with EC who were admitted to our hospital from January 2005 to December 2017 and met the inclusion criteria.The 5-year overall survival (OS), progression-free survival (PFS) and pattern of recurrence were analyzed. The Kaplan-Meier method was used to calculate survival rates, Log-rank test for univariate analysis and Cox method for multivariate analysis were used to detect survival difference. Results: 1-year, 3-year and 5-year OS and PFS of the entire group were 65.9% and 45.8%, 34.2% and 25.0%, 27.0% and 18.5%, respectively. Median OS and PFS were 19.4 months (95% CI=18.0-20.7 months) and 10.4 months (95% CI=9.3-11.3 months), respectively. Univariate analysis showed that the sex, KPS, tumor location, T stage, N stage, M stage, TNM stage, radiation dose and treatment modality were prognostic factors for 5-year OS and PFS of EC patients (P<0.05). Multivariate analysis indicated that the sex, KPS, TNM stage, radiation dose and treatment modality were independent prognostic factors for 5-year OS and PFS (P<0.05). Conclusions: EC patients treated with IMRT can obtain a promising survival. The sex, KPS, TNM stage, radiation dose and treatment modality are independent prognostic factors for prognosis.

LncRNA ASB16-AS1 promotes proliferation and inhibits apoptosis of non small cell lung cancer cells by activating the Wnt/ß catenin signaling pathway.

The article "LncRNA ASB16-AS1 promotes proliferation and inhibits apoptosis of non small cell lung cancer cells by activating the Wnt/ß catenin signaling pathway, by L.-J. Tan, J.-T. Liu, M. Yang, T. Ju, Y.-S. Zhang, published in Eur Rev Med Pharmacol Sci 2020; 24 (4): 1870-1876-DOI: 10.26355/eurrev_202002_20365-PMID: 32141556" has been withdrawn from the authors due to due to some inaccuracies (some data cannot be repeated by our further research). The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/20365.

[Epidemiological characteristic and current status of surgical treatment for esophageal cancer by analysis of national registry database].

Objective: To investigate the epidemiological characteristics and current status of surgical management for esophageal cancer in China. Methods: A national database was setup through a network platform. The clinical data of esophageal cancer treated by surgery was collected from 70 major hospitals in China between January 2009 and December 2014. Results: Complete data of 8 181 cases of esophageal cancer patients who underwent surgery were recorded in the database and recruited in the analysis. Among them, 6 052 cases were male and 2 129 were female, the average age was 60.5 years.The epidemiological investigation results showed that 148 cases (1.8%) had history of psychological trauma, 7 527 cases (92.0%) were lower social economic status, 5 072 cases (62.0%) were short of fresh vegetables and fruits, 6 544 cases (80.0%) ate rough food frequently, 3 722 cases (45.5%) drank untreated water directly from lake or river or shallow well, 3 436 cases (42.0%) had a unhealthy eating habit, including habits of eating food fast (507 cases, 6.2%), eating hot food or drinking hot tea/soup (998 cases, 12.2%), eating fried food (1 939 cases, 23.7%), 4 410 cases (53.9%) had the habits of smoking cigarettes and 2 822 cases (34.5%) drank white wine frequently.The pathological results showed that 7 813 cases (95.5%) were squamous cell carcinoma, 267 cases were adenocarcinoma (3.3%), 25 cases were adenosquamous cell carcinoma (0.3%) and 50 cases were small cell carcinoma (0.6%). A total of 1 800 cases (22.0%) received preoperative neoadjuvant therapy due to locally advanced disease or difficulty of resection. The esophagectomies were performed through left thoracotomy approach in 5 870 cases (71.8%), through right chest approach in 2 215 cases (27.1%), and the remain 96 cases (1.2%) received surgery though other approaches.A total of 8 001 cases (97.8%) underwent radical resection, the other 180 cases (2.2%) received palliative resection. The 30-day postoperative mortality rate was 0.5%, the overall ≥ grade Ⅱ postoperative complication rate was 11.6% (951 cases). The 1-yr, 3-yr, and 5-yr overall actual survival rates were 82.6%, 61.6%, and 52.9%, respectively. Conclusions: The data analysis of the national database for esophageal cancer shows that bad eating habits or eating rough food without enough nutrients, lower social and economic status, drinking white wine and smoking cigarettes frequently may be correlated with tumorigenesis of esophageal cancer. However, strong evidences produced by prospective observation studies are needed. Overall, the long-term survival of esophageal cancer patients has been improved gradually due to the application of advanced surgical techniques and reasonable multimodality treatment.

LncRNA ASB16-AS1 promotes proliferation and inhibits apoptosis of non small cell lung cancer cells by activating the Wnt/ß catenin signaling pathway.

OBJECTIVE: To detect the expression of long non-coding ribonucleic acid (lncRNA) ASB16-AS1 in non-small cell lung cancer (NSCLC) tissues and cells, and to explore the effect of lncRNA ASB16-AS1 on the biological functions of NSCLC cells. PATIENTS AND METHODS: The expression level of lncRNA ASB16-AS1 in NSCLC tissues and cells was detected via real-time fluorescence quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR). The interference sequences of lncRNA ASB16-AS1 were designed and synthesized, and its transfection efficacy was detected by qRT-PCR. After knockdown of lncRNA ASB16-AS1, the proliferation, cell cycle, and apoptosis of NSCLC cells were detected via cell counting kit-8 (CCK-8) assay, colony formation assay, and flow cytometry, respectively. Moreover, the expression changes in the Wnt/ß catenin signaling pathway were detected via Western blotting. RESULTS: LncRNA ASB16-AS1 was upregulated in NSCLC tissues and cells compared with that in paracarcinoma tissues and 16HBE cells. The results of CCK-8 assay and colony formation assay revealed that the silence of lncRNA ASB16-AS1 attenuated the proliferative ability in NSCLC. The results of flow cytometry manifested that the silence of lncRNA ASB16-AS1 arrested the cell cycle in G0/1 phase, and accelerated the apoptosis rate. The key proteins in the Wnt/ß-catenin signaling pathway were regulated by lncRNA ASB16-AS1 in NSCLC. CONCLUSIONS: LncRNA ASB16-AS1 is upregulated in NSCLC tissues and cells, which promotes proliferation and inhibits apoptosis of NSCLC cells through the Wnt/ß-catenin signaling pathway.

Maximizing the impact of, and sustaining standing orders protocols for adult immunization in outpatient clinics.

BACKGROUND: Low adult immunization rates leave adults at risk from infectious disease, and the resulting complications of vaccine-preventable diseases. Standing orders protocols (SOPs) for adult immunization have not been implemented widely in clinics serving adult patients. Our purpose was to evaluate the impact of SOPs on adult immunization rates and identify challenges to sustaining adult immunization coverage rates after implementation of SOPs. METHODS: Baseline adult vaccination rates were calculated for the year prior to SOPs implementation in 5 diverse clinics. Vaccines included in the implemented standing orders included Tdap, influenza, pneumococcal, human papillomavirus, herpes zoster, and hepatitis B. Adult vaccination rates were tracked for 1 year after SOPs implementation. RESULTS: Sites generally sustained modest gains in coverage rates (4%-8% increase) after SOP implementation, but greater success was found in practices that used SOPs as a foundation on which additional interventions were built. Challenges to increasing coverage rates included prioritization of acute and chronic conditions over adult vaccination, Medicare Part D reimbursement policies, electronic medical record issues related to data reporting and programming for patient alerts, and the lack of interoperability between the state immunization information system (missing patient vaccination history) and electronic medical record. CONCLUSIONS: SOPs may provide a good starting point for increasing adult immunization coverage rates. Using additional interventions, quality-based metrics, or incentives could lead to sustained adult immunization prioritization.

[Advances in osteoradionecrosis of nasopharynx after radiotherapy for nasopharyngeal carcinoma].

Radiation therapy is the first choice for the treatment of nasopharyngeal carcinoma. However, it is inevitable that nasopharyngeal mucosa and tissue will be damaged after radiotherapy of nasopharyngeal carcinoma, which will cause corresponding complications. Nasopharyngeal osteonecrosis is a serious complication. Up to now, there are few reports about nasopharyngeal osteonecrosis, and the underlaying pathological mechanism remains unclear. The potential theories include radiotherapy damage, infection and trauma, but also the " three H" principle of hypoxic hypocellular hypovascular tissue, as well as the theory of radio induced fibrosis. It is controversial about the treatment of nasopharyngeal osteonecrosis. It takes comprehensive treatment, including local treatment, systemic treatment, surgical treatment and other treatments. Among them, local treatment as nasopharyngeal debridement usually is first choice. We reviewed the pathological mechanism and treatment methods of nasopharyngeal osteonecrosis, in order to provide a reference for better prevention and treatment of it.

Epigenomic elements analyses for promoters identify ESRRG as a new susceptibility gene for obesity-related traits.

OBJECTIVES: With ENCODE epigenomic data and results from published genome-wide association studies (GWASs), we aimed to find regulatory signatures of obesity genes and discover novel susceptibility genes. METHODS: Obesity genes were obtained from public GWAS databases and their promoters were annotated based on the regulatory element information. Significantly enriched or depleted epigenomic elements in the promoters of obesity genes were evaluated and all human genes were then prioritized according to the existence of the selected elements to predict new candidate genes. Top-ranked genes were subsequently applied to validate their associations with obesity-related traits in three independent in-house GWAS samples. RESULTS: We identified RAD21 and EZH2 as over-represented, and STAT2 (signal transducer and activator of transcription 2) and IRF3 (interferon regulatory transcription factor 3) as depleted transcription factors. Histone modification of H3K9me3 and chromatin state segmentation of 'poised promoter' and 'repressed' were over-represented. All genes were prioritized and we selected the top five genes for validation at the population level. Combining results from the three GWAS samples, rs7522101 in ESRRG (estrogen-related receptor-γ) remained significantly associated with body mass index after multiple testing corrections (P=7.25 × 10(-5)). It was also associated with ß-cell function (P=1.99 × 10(-3)) and fasting glucose level (P<0.05) in the meta-analyses of glucose and insulin-related traits consortium (MAGIC) data set.Cnoclusions:In summary, we identified epigenomic characteristics for obesity genes and suggested ESRRG as a novel obesity-susceptibility gene.

[Survival and prognostic evaluation of superficial esophageal cancer after surgery].

OBJECTIVE: To calculate the survival rate of patients with superficial esophageal squamous carcinoma who received esophageal resection and to explore factors that affect prognosis. METHODS: There were 285 patients with pTis-T1 esophageal carcinoma who underwent esophagectomy during 2007-2011. Their cumulative survival rates were calculated using life tables. Nine factors that may have impact on postoperative survival of superficial esophageal carcinoma were selected. The Kaplan-Meier method and COX's regression model were used to select prognostic factors, estimate prognostic index, and establish risk stratification. RESULTS: The 1-, 3- and 5-year overall survival rates of superficial esophageal carcinoma patients were 97%, 86%, and 82%, respectively. Tumor length, stenosis, depth of invasion, differentiation degree, lymph node metastasis, and vascular tumor thrombus were associated with prognosis according to univariate analysis. Depth of invasion (OR=2.065, P=0.029), lymph node metastasis (OR=2.049, P=0.041), differentiation degree (OR=3.828, P=0.000), stenosis(OR=2.129, P=0.048), and vascular tumor thrombus (OR=4.222, P=0.004) were independent prognostic factors in multivariate analysis. A prognostic models was thus established and all the patients were divided into low-risk, moderate-risk and high-risk group, with the 3-year survival rates being 95%, 84%, and 51%, and 5-year survival rates being 93%, 79%, and 44%, respectively. CONCLUSIONS: Patients with superficial esophageal cancer have relatively favorable prognosis. Depth of invasion, differentiation degree, stenosis, lymph node metastasis, and vascular tumor thrombus may be independent factors of poor prognosis. Survival rate of moderate- and high-risk patients is yet to be improved.

Autophagic and apoptotic cell death in amniotic epithelial cells.

The aim of this paper is to determine if autophagic cell death is associated with apoptosis and whether it participates in the process of term amniotic rupture. Forty pieces of fresh term amnions, including twenty from a position near the margin of the placentas and twenty from the margin of the naturally ruptured part of the placentas in term gestation were collected, respectively. The amnions were examined by scanning electron microscopy (SEM) and amniotic epithelial (AE) cells were examined by transmission electron microscopy (TEM). Autophagic and apoptotic cell death (PCD) were assayed by laser scanning confocal microscopy (LSCM) or flow cytometry using monodansylcadaverin (MDC) and propidium iodide (PI) stain. BCL(2) and BAX were examined by immunoblotting. Under SEM the amniotic epithelia appeared normal in the position near the placenta. They had an atrophied appearance in the margin of their natural broken parts. In the AE cells PCD was divided into three subtypes by TEM: autophagic cell death with positive stains of MDC and PI; apoptotic cell death; and the mixed type. Quantitative detection showed that there were more death cells, including autophagic and apoptotic, in the AE cells near the ruptured parts than near the placentas. An increased expression of BAX and a decreased expression of BCL(2) protein in the AE cells near the broken margin were observed. Apoptotic and autophagic cell death by the intrinsic pathway are the basic event in the AE cell and they are involved in the cause of membrane rupture of the human amnion in term gestation.

The relationship between solitary pulmonary nodules and bronchi: multi-slice CT-pathological correlation.

AIM: To investigate the relationship between solitary pulmonary nodules (SPN) and bronchi and its value in predicting the nature of the SPN. MATERIALS AND METHODS: We performed volumetric targeted scans of 0.5 mm collimation with multi-slice computed tomography (MSCT), reconstructing multiplanar reconstructions (MPR), curved multiplanar reconstructions (CMPR) and surface-shaded display (SSD) images of bronchi in 78 consecutive patients with SPN (53 malignant and 25 benign) and correlated the findings with those of macroscopic and microscopic specimens. RESULTS: With this CT protocol, the third to seventh-order bronchi were shown continuously and very clearly in all patients. CT findings were consistent with those of specimens. CT demonstrated the relationship between the SPN and bronchi in 46 (86.8%) malignant and 18 (75.0%) benign nodules. Five types of tumour-bronchus relationships were identified with MSCT. Type I: the bronchus was obstructed abruptly by the SPN; type II: the bronchus penetrated into the SPN with tapered narrowing and interruption; type III: the bronchial lumen shown within the SPN was patent and intact; type IV: the bronchus ran around the periphery of the SPN with intact lumen; type V: the bronchus was displaced, compressed and narrowed by the SPN. Malignant nodules were most commonly of type I (58.5%), secondly of type IV (26.4%) and rarely of type V (1.9%). Benign nodules were most often of type V (36.0%), followed by type III (20.0%), type I (16.0%), and there were no type II. Types I, II and IV were more common in malignant nodules, whereas type V was seen more frequently seen in benign nodules (p<0.05). There was no statistically significant difference between the two groups regarding type III. CONCLUSION: Ultra-thin section with MSCT and MPR, CMPR and SSD reconstruction can improve the demonstration of the patterns of tumour-bronchus relationships, which can reflect the pathological changes of the nodules to some extent and help differentiate malignant from benign tumours.

Endogenous presentation of self myelin epitopes by CNS-resident APCs in Theiler's virus-infected mice.

The mechanisms underlying the initiation of virus-induced autoimmune disease are not well understood. Theiler's murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD), a mouse model of multiple sclerosis, is initiated by TMEV-specific CD4(+) T cells targeting virally infected central nervous system-resident (CNS-resident) antigen-presenting cells (APCs), leading to chronic activation of myelin epitope-specific CD4(+) T cells via epitope spreading. Here we show that F4/80(+), I-A(s+), CD45(+) macrophages/microglia isolated from the CNS of TMEV-infected SJL mice have the ability to endogenously process and present virus epitopes at both acute and chronic stages of the disease. Relevant to the initiation of virus-induced autoimmune disease, only CNS APCs isolated from TMEV-infected mice with preexisting myelin damage, not those isolated from naive mice or mice with acute disease, were able to endogenously present a variety of proteolipid protein epitopes to specific Th1 lines. These results offer a mechanism by which localized virus-induced, T cell-mediated inflammatory myelin destruction leads to the recruitment/activation of CNS-resident APCs that can process and present endogenous self epitopes to autoantigen-specific T cells, and thus provide a mechanistic basis by which epitope spreading occurs.

Arsenic trioxide induces apoptosis of oesophageal carcinoma in vitro.

The arsenic compounds in traditional Chinese medicine have been recorded to have therapeutic effects on the treatment of psoriasis, syphilis, rheumatosis and a number of malignant tumours. Recent studies showed that arsenic trioxide can induce clinical remission in patients with acute promyelocytic leukemia, including those who have relapsed after retinoic acid treatment. however, the mechanism of how arsenic trioxide targets tumour cells is not clearly understood. We have examined the effects of arsenic trioxide on oesophageal carcinoma cell line EC8712. Our results demonstrated that the growth and survival of tumour cells were markedly inhibited by arsenic trioxide. The half dose effect (ED50) was at the concentration of 1 microM. Electron microscopic study demonstrated that EC8712 tumour cells treated with arsenic trioxide display a typical morphological appearance of apoptosis, including chromatin condensation and fragmentation of the nuclei. In contrast, no apoptotic features were observed in tumour cells without arsenic trioxide treatment. TUNEL assay also showed the biological features of apoptosis in cells treated with arsenic trioxide. Flow cytometry analyses showed that apoptotic peak was identified in arsenic trioxide treated cells but not in the control. Apoptotic cells in arsenic trioxide treated group account for 35% of total cell populations after three days treatment at a dose of 3 microM. In short, our results suggested that the anticancer effect of arsenic trioxide is due, at least in part, to the induction of apoptosis in cancer cells.

[Experimental study on the induced-differentiation of human esophageal cancer cells treated with dimethylsulfoxide].

The fact that treatment of leukemia (Acute Promyelocytic Leukemia) with ATRA (All-Trans Retinoic Acid) was so succeeded that it was considered as a good example for tumor therapy. In the treatment of solid tumors by means of induced differentiation, however, has not been yet so broken-through. DMSO (Dimethylsulfoxide) was a common and simple organic compound, which comprised a variety of biological activities. For example, DMSO induced differentiation of leukemia in many reports. However, the effect of DMSO on solid tumors was to be explored further. In the present study, DMSO was used to human esophageal cancer cell lines in vitro in comparison with the classical inducer ATRA. From the view of morphology, cell cycle, growth inhibition, cytokeratin 4 expression, dye transfer and tumorigenecity, the results demonstrated that DMSO as well as ATRA could induce differentiation of human esophageal cancer cells. Interestingly, DMSO was confirmed to be more effective in inducing differentiation of esophageal cancer cells than ATRA. It suggests that DMSO showed some good prospects for the treatment of solid tumors.

[Research on the activity and quantity of natural killer cells and T lymphocytes in myelodysplastic syndrome patients].

24 patients with myelodysplastic syndrome (MDS) were examined for the following items. T lymphocyte subsets of five subtypes of MDS examined with monoclonal antibody were less than that in normal controls. After incubation of peripheral blood lymphocytes with PHA at 37 degrees C with 5% carbon dioxide, the amount of HLA-DR positive cells and NKH1 positive cells were less than normal, NK cell activity was measured with cytotoxicity assay using 51 Cr labeled target K562 cells, the results showed that NK activity in MDS was less than that in controls. As mentioned above, the results indicated that the activity and quantity of T lymphocytes and NK cells in MDS were abnormal.

Regulation of the effector stages of experimental autoimmune encephalomyelitis via neuroantigen-specific tolerance induction. II. Fine specificity of effector T cell inhibition.

Ag-specific tolerance induced by the i.v. administration of splenocytes coupled with mouse spinal cord homogenate, containing a mixture of myelin Ag, dramatically inhibits development and expression of clinical and histologic signs of both active and adoptive forms of relapsing experimental autoimmune encephalomyelitis (R-EAE) in the SJL/J host. Here we examined the dose-dependency, route of tolerogen administration, and fine neuroantigen specificity of inhibition of adoptive R-EAE. Expression of clinical R-EAE induced by a polyclonal population of bovine myelin basic protein (MBP)-specific effector T cells was dramatically inhibited in a dose-dependent manner following the i.v., but not s.c. or i.p., injection of MBP-coupled splenocytes. The exquisite Ag specificity of the inhibition was evident by the observation that splenocytes coupled with intact bovine MBP or species variants of MBP homologous with bovine MBP within the major encephalitogenic region (amino acids 84-104), but not with proteolipid protein or mouse kidney homogenate, were able to suppress disease expression. Splenocytes coupled with the MBP84-104 peptide, containing a nested set of the major SJL/J encephalitogenic epitopes, completely inhibited peptide-specific T cell responses, but only partially inhibited the expression of disease transferred by T cells specific for intact MBP, suggesting the participation of T cell responses specific for additional MBP determinants in disease pathogenesis. However, splenocytes coupled with previously identified minor SJL/J encephalitogenic epitopes (MBP91-104 or MBP17-27), or with the Lewis rat major encephalitogenic epitope (MBP68-86), did not suppress disease expression. Collectively, the results demonstrate that MBP84-104-specific T cells and T cells specific for an as yet unidentified MBP epitope(s) contribute to the pathology of R-EAE. In addition, the results demonstrate that peptide-specific tolerance induction appears to have potential for the treatment of T cell-mediated inflammatory diseases.