Ⅰ期结直肠癌局部复发与转移18例患者的临床病理特征分析

目的探讨早期结直肠癌复发与转移的高危因素、诊断与治疗现状,以期改善预后。 方法回顾性总结2005年3月至2008年5月中国医学科学院肿瘤医院收治的18例Ⅰ期、无脉管瘤栓与神经侵犯但出现复发及转移的结直肠癌患者临床病理资料。 结果18例Ⅰ期局部复发与远处转移的结直肠癌患者中,男性12例（66.7%）,女性6例（33.3%）,术前便血15例（83.3%）,无体重减轻11例（64.7%）,T1肿瘤2例（11.1%）,T2肿瘤16例（88.9%）,局部复发7例（38.9%）,远处转移9例（50.0%）,淋巴结转移2例（11.1%）。11例患者（61.11%）的复发与转移没有临床症状。复发转移后中位生存期为57.6个月。 结论Ⅰ期结直肠癌患者必须常规进行定期复查,要重视复发与转移的早期症状。     

肺癌转移与术后复发患者血清CEA、CA211水平的临床意义

目的探讨CEA、CYFRA21-1两种肿瘤标志物的血清水平对肺癌转移和术后复发的诊断价值。方法应用化学发光免疫检测正常组、复发组、转移组CEA、CYFRA21-1的血清水平和阳性率,并进行统计学分析。结果复发组和转移组血清CEA、CYFRA21-1水平都显著高于正常对照组(P0.05),CEA、CYFRA21-1在复发组中阳性率分别为53.46%、56.67%,在转移组中阳性率分别57.78%、62.22%,两种标志物联检复发组和转移组的阳性率分别为83.33%、88.89%。结论CEA、CYFRA21-1具有诊断肺癌复发和转移的临床价值,两者联检可以提高诊断的准确性。     

Suppression of colorectal cancer metastasis by nigericin through inhibition of epithelial-mesenchymal transition

AIM: To evaluate the effect of nigericin on colorectal cancer and to explore its possible mechanism.METHODS: The human colorectal cancer (CRC) cell lines HT29 and SW480 were treated with nigericin or oxaliplatin under the conditions specified. Cell viability assay and invasion and metastasis assay were performed to evaluate the effect of nigericin on CRC cells. Sphere-forming assay and soft agar colony-forming assay were implemented to assess the action of nigericin on the cancer stem cell properties of CRC cells undergone epithelial-mesenchymal transition (EMT).RESULTS: Compared with oxaliplatin, nigericin showed more toxicity for the HT29 cell line (IC50, 12.92 ± 0.25 μmol vs 37.68 ± 0.34 μmol). A similar result was also obtained with the SW116 cell line (IC50, 15.86 ± 0.18 μmol vs 41.02 ± 0.23 μmol). A Boyden chamber assay indicated that a significant decrease in the number of HT29 cells migrating through polyvinylidene fluoride membrane was observed in the nigericin-treated group, relative to the vehicle-treated group [11 ± 2 cells per high-power field (HPF) vs 19.33 ± 1.52 cells per HPF, P < 0.05]. Compared to the control group, the numbers of HT29 cells invading through the Matrigel-coated membrane also decreased in the nigericin-treated group (6.66 ± 1.52 cells per HPF vs 14.66 ± 1.52 cells per HPF, P < 0.05). Nigericin also reduced the proportion of CD133⁺ cells from 83.57% to 63.93%, relative to the control group (P < 0.05). Nigericin decreased the number of spheres relative to the control group (0.14 ± 0.01 vs 0.35 ± 0.01, P < 0.05), while oxaliplatin increased the number of spheres relative to the control group (0.75 ± 0.02 vs 0.35 ± 0.01; P < 0.05). Nigericin also showed a decreased ability to form colonies under anchorage-independent conditions in a standard soft agar assay after 14 d in culture, relative to the control group (1.66 ± 0.57 vs 7 ± 1.15, P < 0.05), whereas the colony numbers were higher in the oxaliplatin group relative to the vehicle-treated controls (14.33 ± 0.57 vs 7 ± 1.15, P < 0.05). We further detected the expression of E-cadherin and vimentin in cells treated with nigericin and oxaliplatin. The results showed that HT29 cells treated with nigericin induced an increase in E-cadherin expression and a decrease in the vimentin expression relative to vehicle controls. In contrast, oxaliplatin downregulated the expression of E-cadherin and upregulated the expression of vimentin in HT29 cells relative to vehicle controls.CONCLUSION: This study demonstrated that nigericin could partly reverse the EMT process during cell invasion and metastasis.     

尼美舒利抑制结肠癌LOVO细胞增殖及转移的机制

目的 研究选择性COX2抑制剂尼美舒利(Nimesulide)对结肠癌细胞株LOVO生长的影响以及其参与抑制肿瘤血管转移的可能机制.方法 采用四甲基偶氮唑蓝(MTT)比色法观察尼美舒利对结肠癌细胞增殖的抑制,电镜下观察尼美舒利作用后细胞的超微结构变化,ELISA法检测尼美舒利对上清液中血管内皮生长因子(VEGF)的影响.结果 MTT显示尼美舒利能抑制LOVO的增殖,呈剂量和浓度依赖性.0.2 mmol/L尼美舒利作用72 h后电镜观察可见典型的凋亡小体.尼美舒利作用后上清液中VEGF的含量呈剂量依赖性下调.结论 尼美舒利可抑制结肠癌细胞株LOVO的生长,促进其凋亡,还可下调细胞上清中的VEGF含量,推测其通过抑制VEGF释放,从而抑制肿瘤的生长及浸润转移.     

The impact of the number of occult metastatic lymph nodes on postoperative relapse of resectable esophageal cancer

Clinical stage II/III esophageal cancer (EC), as defined by the Japanese Classification, relapses at a moderately high rate even after curative resection. The number of lymph node metastases is known to be associated with tumor relapse. Recently, the prognostic significance of occult metastatic lymph nodes (MLNs), as well as that of overt MLNs, has been reported. The aim of this study was to investigate the impact of the total number of MLNs including occult MLNs on postoperative relapse in clinical stage II/III EC. One hundred and five patients with clinical stage II/III EC who underwent esophagectomy accompanied by radical lymphadenectomy at the Department of Surgical Oncology in Osaka City University Hospital between January 2000 and October 2008 were included in this study. Occult MLNs, metastases not detected by hematoxylin‐eosin staining, were identified by immunohistochemistry (IHC) using antipancytokeratin antibody AE1/AE3. The clinicopathological features of occult MLNs were compared between the relapse and no relapse groups. A total of 6558 lymph nodes (1357 from two‐field dissection and 5201 from three‐field dissection) were examined by IHC staining; 362 overt MLNs and 143 occult MLNs were detected. The number of occult MLNs increased in proportion to the International Union Against Cancer pathological (p)N‐status and pStage. When the number of occult MLNs was added to the number of pNs, the number of total MLNs was associated with postoperative relapse. With respect to tumor, node, metastasis stage, 6 of 22 patients (27%) who were pathological node‐negative converted to node‐positive by considering total MLNs. The number of N3 patients with relapse increased markedly with restaging by total MLNs. The number of total MLNs, but not overt MLNs, was an independent prognostic factor on multivariate analysis. These results suggest that occult MLNs were often found, and they were associated with postoperative relapse of resectable esophageal cancer. The total number of MLNs including occult MLNs could contribute to evaluating the precise stage of patients with esophageal cancer.     

肝癌干细胞与肝癌复发转移的研究进展

影响肝癌预后的因素很多,其中包括确诊时间过晚、合并肝硬化、肿瘤细胞对放化疗不敏感以及术后的转移与复发等.以往对肝癌复发转移的研究重点在:(1)肝癌细胞的脱落、迁移;(2)肝癌细胞在局部组织的黏附;(3)肝癌细胞周围血管的生成.随着对肝癌干细胞的研究报道,使我们对肝癌的转移和复发有了更进一步的认识.本文通过基因层面对肝癌...     

A novel ferroptosis-related long noncoding RNA signature for relapse free survival prediction in patients with breast cancer

Ferroptosis is the process of cell death dependent on iron. Growing evidence suggests that ferroptosis plays vital roles in the biological process of many cancers. However, just a small number of ferroptosis-related lncRNAs have been explored in depth.Ferroptosis-related lncRNAs in breast cancer (BC) were identified by co-expression analysis based on The Cancer Genome Atlas database (TCGA). The whole set was divided into a training set and a test set with a 1:1 ratio. Univariate Cox regression and LASSO analyses were performed to establish a signature in the 3 sets. Kaplan-Meier analysis and receiver operating characteristic (ROC) for the 3 sets validated the effectiveness and robustness of the signature. Besides, we also explore the relationship between this and clinical characteristics, immune cell infiltration and tumor microenvironment. Meanwhile, the nomogram was drawn by screening indicators of independent recurrent prediction. Finally, we evaluated the relationships between the signature and tumor microenvironment.We identified 391 ferroptosis-related lncRNAs and constructed a 5 lncRNAs-based signature in the training, test, and whole sets, stratifying patients into high-risk and low-risk groups. According to survival analysis, patients in the high-risk groups had worse relapse free survival (RFS) compared to the low risk-groups. The ROC curves indicated that the recurrent signature had a promising predictive capability for BC patients. Moreover, an independent factors-based nomogram model could offer the quantitative prediction and net benefit for the recurrence of BC patients. Finally, the microenvironment, including tumor mutational burden (TMB), immune cell functions and immune checkpoints, showed big differences between the 2 groups.The 5 ferroptosis-related lncRNAs and their signature might be novel promising biomarkers and immunotherapy targets for patients with BC.     

Alcohol relapse and near-relapse experiences show that relapse models need to be updated

Why do people with Alcohol Use Disorder [AUD] frequently relapse after completing treatment? This study examines the experience of relapse compared to near-relapse, thereby illustrating the difference between relapsing and staying abstinent when faced with a high-risk situation. Through twelve qualitative interviews and subsequent Interpretive Phenomenological Analysis, we found that the experiences could be understood in terms of two themes: a) regulation of self, and b) the role of other people. Relapse specifically was characterized by the use of alcohol as a means of self-regulation combined with the sense of being disconnected from other people. The implications are that current relapse models need to place more emphasis on the interpersonal aspects of relapsing. The implications for practice are that AUD patients should be assisted in building new and/or strengthening existing ties to social networks.     

Effect of cisapride on relapse of esophagitis

The effect of a prokinetic agent, cisapride, on the relapse of reflux esophagitis was investigated in a randomized, double-blind trial conducted in 443 patients whose esophagitis had previously been healed with an acid antisecretory drug. Patients received cisapride, 20 mg at night, cisapride 10 mg twice daily, or placebo for 12 months or until endoscopic relapse was confirmed endoscopically. In 88% of all patients (respectively 133, 132, and 124), endoscopic data were available at discontinuation of treatment. In comparison with placebo, the two cisapride regimens prolonged both the time to endoscopically confirmed relapse (Kaplan-Meier analysis;P=0.001) and the time to symptomatic relapse (P=0.012). The life-table endoscopic relapse rates at 12 months were 51% for placebo, 32% for cisapride 20 mg at night (P=0.005), and 34% for cisapride 10 mg twice daily (P=0.02). Patients with more severe esophagitis before healing relapsed more rapidly during maintenance therapy, regardless of the treatment regimen. Adverse events were infrequent in all three groups. These findings indicate that maintenance treatment with the prokinetic drug cisapride prevents the relapse of esophagitis after it has been healed by acid antisecretory therapy.This work was supported by the Janssen Research Foundation and the Swiss National Foundation. Grant SNF 32-26369.89.     

The Wee1 kinase inhibitor MK1775 suppresses cell growth,attenuates stemness and synergises with bortezomib in multiple myeloma

Multiple myeloma stem-like cells (MMSCs) are responsible for initiation and relapse, though novel treatment paradigms that effectively eradicate MMSCs are yet to be developed. Selective inhibition of the cell cycle regulatory kinase Wee1 by MK1775 is being explored as a potential anti-cancer therapeutic. We report that higher expression of Wee1 is correlated with poor survival in multiple myeloma (MM). The MM models and patient-derived CD138⁺ plasma cells are particularly sensitive to the growth-inhibitory effects of the Wee1 inhibitor MK1775. MK1775 induces Mus81-Eme1 endonuclease-mediated DNA damage in S-phase cell cycle that results in a blockade of replication and then apoptosis. Furthermore, MK1775 strongly suppresses the features of stemness in vitro, in vivo and in primary CD138⁺ cells by decreasing ALDH1⁺ cell fraction and the expression of ALDH1. In addition, co-treatment of MK1775 with bortezomib is synergistic in vitro and in vivo. Bortezomib, although it enhances ALDH1⁺ cells, when combined with MK1775 abrogates this stimulatory effect on stemness. Considering MM as an invariably incurable malignancy due to the presence of heterogenic myeloma stem-like cells, our study presents inhibition of Wee1 as a promising targeted therapy for MM and provides a compelling rationale to further investigate the activity of MK1775 against myeloma in clinical settings.     

Suppression of gastric cancer growth by adenovirus-mediated transfer of the PTEN gene

AIM: To investigate the tumor-suppressive effect of the phosphatase and tensin homologue deleted from chromosome (PTEN) in human gastric cancer cells that were wild type for PTEN. METHODS: Adenoviruses expressing PTEN or luciferase as a control were introduced into gastric cancer cells. The effect of exogenous PTEN gene on the growth and apoptosis of gastric cancer cells that are wtPTEN were examined in vitro and in vivo. RESULTS: Adenovirus-mediated transfer of PTEN (AdPTEN) suppressed cell growth and induced apoptosis significantly in gastric cancer cells (MGC-803, SGC-7901) carrying wtPTEN in comparison with that in normal gastric epithelial cells (GES-1) carrying wtPTEN. This suppression was induced through downregulation of the Akt/PKB pathway, dephosphorylation of focal adhesion kinase and mitogen-activated protein kinase and cell-cycle arrest at the G2/M phase but not at the G1 phase. Furthermore, treatment of human gastric tumor xenografts (MGC-803, SGC-7901) with Ad-PTEN resulted in a significant (P<0.01) suppression of tumor growth. CONCLUSION: These results indicate a significant tumor-suppressive effect of Ad-PTEN against human gastric cancer cells. Thus, Ad-PTEN may be used as a potential therapeutic strategy for treatment of gastric cancers.     

Risk of relapse and clinico-pathological features in 103 patients with diffuse large-cell lymphoma in complete response after first-line treatment

Abstract: Patients with diffuse large-cell lymphoma (DLCL) achieve a complete response (CR) in most cases, but at least one-third of them eventually relapse. Such an event occurs most frequently within 2 yr from CR achievement. The aim of the present study was to analyse the risk and pattern of relapse of patients with DLCL in CR. One hundred and three patients with DLCL (53 male/50 female; median age: 55 yr) in CR after doxorubicin-containing first-line treatments were included in the study. Main clinicobiological characteristics at diagnosis and at relapse were analysed. Uni- and multivariate studies were performed. Forty-one patients (40%) eventually relapsed, in 27 cases within 2 yr from CR and 14 thereafter. Histological subtype was the same at diagnosis and at relapse in all the early relapsing patients and in 8 of 10 late relapsing patients with available biopsy. The most important variables at diagnosis for predicting relapse were advanced stage (p < 0.01) and bone marrow infiltration (p = 0.05), with stage (I–II vs. III–IV) (p = 0.009; relative risk = 2.28) being the only predictive variable in the multivariate analysis. No differences were found according to the treatment given. The second CR rate obtained in the late relapsing patients after salvage therapies was higher that in early relapsing (50% vs. 37%). Median survival from relapse was 1.4 yr for patients early relapsing and it was not achieved for those with late relapses (p = 0.09). Late relapse is a quite common event in DLCL lymphomas, with those patients achieving more frequently a second CR and having better survival than early relapsed patients.     

Intraocular relapse of childhood acute lymphoblastic leukaemia

Relapse of childhood acute lymphoblastic leukaemia (ALL) involving the eye is a rare but challenging problem. Twenty cases occurred in patients treated on the Medical Research Council United Kingdom Acute Lymphoblastic Leukaemia XI and ALL97 trials between 1991 and 2001, representing 2.2% of ALL relapses. Seventeen occurred as a first relapse, either in isolation or combined with relapse at another site, and three occurred as a second relapse. All patients with intraocular disease at first relapse were treated with both chemotherapy and radiotherapy, but the doses and protocols used varied. Eleven of these 17 patients are alive and in complete remission with a median follow up of 4 years 2 months from relapse. All 11 children that were treated with a full chemotherapy relapse protocol, together with local radiotherapy have survived. Patients treated with chemotherapy of shorter duration and intensity, despite radiotherapy and/or bone marrow transplantation, did poorly with only one survivor, currently in chronic relapse. Consequently, we suggest that children with eye relapse of ALL be treated with an intensive relapse chemotherapy protocol with local ocular radiotherapy, whether the relapse occurs in isolation or in combination with relapse at another site.     

Pain caused by bone metastasis in endocrine-therapy-refractory prostate cancer

It is of clinical importance to control pain in the management of patients with endocrine-therapy-refractory prostate cancer. To evaluate factors influencing the manifestation of pain and the relationship between characteristics of pain and prognosis, patients with pain from bone metastasis were analyzed. A total of 48 patients with endocrine-therapy-refractory prostate cancer, who showed progression of bone metastasis and were followed-up until death, comprised the present study. The patients were divided into three groups according to the grade of pain: no need for analgesics, a need for non-opioid analgesics, and a need for opioid analgesics. The time interval between the diagnosis of the endocrine-therapy-refractory state and the requirement for analgesics was estimated. Survivals from the endocrine-therapy-refractory state were calculated according to the grade of pain or the time interval to requirement for analgesics. In addition, the extent of disease, the doubling time of tumor markers at the refractory state, any change of alkaline phosphatase, and other prognostic factors were examined in relation to pain. All 22 endocrine-therapy-resistant cases at initial treatment and 18 of 26 (69%) relapsed cases required analgesics during the clinical course until death. No difference in survival was observed between the grades of pain. The patients who needed analgesics within 1 year after becoming refractory to endocrine therapy showed significantly shorter survival than those without or with analgesics more than 1 year later. Although the time elapsing before analgesics were needed was not related to the extent of disease, the patients who showed a shorter doubling time for tumor markers and/or an exponential increase in alkaline phosphatase tended to require analgesics within 1 year. In endocrine-therapy-refractory prostate cancer, the early requirement for analgesics suggests poor prognosis, and the onset of pain may be attributable not to the extent of the disease but rather to the rapid expansion of bone metastasis.Abbreviations PAP prostatic acid phosphatase - PSA prostate-specific antigen This work was supported in part by a Grant-in Aid from the Ministry of Health and Welfare, Japan (5–10)     

间日疟复发及其治疗研究进展

间日疟原虫在世界范围分布广泛,易复发,较恶性疟更难控制和消除。此外,间日疟复发也是疟疾传播的重要途径,复发的相关因素较为复杂,针对复发有多种治疗方案。本文就间日疟复发的机制,相关因素及复发的治疗研究进展作一综述。     

Endobronchial metastasis from stomach cancer

A young woman presented with a dry cough present during the previous 4 weeks. A chest radiograph demonstrated diffuse interstitial infiltration in both lower lung fields. Fibreoptic bronchoscopic examination revealed multiple 2-3 mm elevated nodules on the bronchial surface and a mucosal biopsy showed extensive subepithelial infiltration of poorly differentiated adenocarcinoma without definite precancerous alteration in the overlying epithelium. Studies for the evaluation of primary tumour focus were performed. Oesophagogastroduodenoscopy showed advanced gastric cancer of Borrmann type III, and mucosal biopsy of the stomach showed poorly differentiated adenocarcinoma. The patient was treated three times with systemic chemotherapy, but her condition deteriorated. Three months after diagnosis, she died of complicated pneumonia. This is a rare case of endobronchial metastasis from stomach cancer. The stomach is an unusual site of endobronchial metastasis from extrathoracic primary malignancy.