SHP-1 acts as a tumor suppressor by interacting with EGFR and predicts the prognosis of human breast cancer

Objective:The aims of this study were to examine the prognostic value of SHP-1 in breast cancer, its roles in the regulation of breast cancer cell growth and metastasis, and the underlying mechanisms.Methods:Tumor specimens from 160 patients with breast cancer and 160 noncancerous tissues were used to examine the expression of SHP-1 and to analyze its association with overall survival through Kaplan–Meier and multivariate Cox regression analyses. RNA sequencing data and the expression and clinical importance of SHP-1 in breast cancer were evaluated with data from The Cancer Genome Atlas. In vitro and in vivo assays were performed to elucidate the effects of SHP-1 on breast cancer cell proliferation and invasion. Confocal immunofluorescence and GST pulldown assays were used to demonstrate the interaction between SHP-1 and epidermal growth factor receptor, as well as its downstream pathways. Immunohistochemistry and The Cancer Genome Atlas database were used to investigate the clinical association between SHP-1 and EGFR in human breast cancer.Results:SHP-1 expression was associated with better survival in patients with breast cancer, whereas SHP-1 expression was negatively correlated with EGFR in human breast cancer. Ectopic SHP-1 expression significantly suppressed breast cancer cell proliferation, migration, and invasion. SHP-1 knockdown induced a more invasive phenotype and accelerated cell growth. Mechanistically, EGFR, a protein directly interacting with SHP-1, mediates the SHP-1-induced inactivation of Ras/Erk/GSK3β signaling and its downstream effectors.Conclusions:SHP-1 is an important prognostic biomarker in patients with breast cancer, and the SHP-1-EGFR axis is a promising target for treatment.     

Methods for monitoring cancer cell pyroptosis

Pyroptosis is a form of proinflammatory cell death that depends on the gasdermin family of proteins. The main features of pyroptosis are altered membrane permeability, cell swelling, membrane rupture, and the ability to mobilize a strong immune response. The relationship between pyroptosis and cancer has become a popular topic in immunological research. Multiple strategies for inducing pyroptosis in cancer cells have been developed for cancer therapy, including chemotherapy, small molecule drugs, and nanomedicines. In this review, we systematically discuss recent advances in research on the mechanisms of pyroptosis, and compare pyroptosis with apoptosis and necroptosis from several aspects. The development of various experimental systems has accompanied rapid progress in this field, but little consensus on monitoring pyroptosis is currently available. We focus on techniques commonly used to monitor pyroptosis, and describe future techniques that may be used to increase our knowledge in this field. Overall, the advancement of pyroptosis detection methods will help researchers to better investigate the relationships between pyroptosis and various cancers, and should provide insights into the use of these promising tools for cancer treatments.     

Diagnosing pancreatic cancer in general practice: a cross-sectional study on associations between suspicion of cancer,urgent referral and time to diagnosis

ObjectiveThis study aimed to investigate the first point of contact in patients diagnosed with pancreatic cancer, and to study factors associated with the GP’s suspicion of cancer, Cancer Patient Pathway (CPP) referral and long diagnostic interval.DesignCross-sectional study combining register and survey data.PatientsPatients with incident pancreatic cancer recorded in the Danish National Patient Register (n = 303).Main outcome measuresThe patient’s first point of symptoms presentation, GP’s cancer suspicion, CPP referral and diagnostic interval.ResultsGeneral practice was the first point of contact for 85.5% of the population. At the first consultation, cancer was suspected in 32.7% and 22.9% were referred to a CPP. The GPs were more likely to suspect cancer or serious illness in patients aged >70 years (prevalence rate ratio (PRR) 1.34, 95% CI 1.09–1.66) and among patients with high comorbidity (PRR 1.23, 95% CI 1.04–1.47). A CPP referral was less likely among patients with low education. The median diagnostic interval was 39 days (interquartile range: 15–72). When the GP initially did not suspect cancer, the likelihood of longer diagnostic interval increased.ConclusionThe majority of patients with pancreatic cancer began their diagnostic route in general practice. Diagnosing pancreatic cancer swiftly in general practice was challenging; the GP did often not initially suspect cancer or refer to a CPP and several of the patient characteristics were associated with the GPs initial suspicion of cancer or CPP referral. Thus, there may be room for improvements in the diagnostics of pancreatic cancer in general practice.

Key points

• Patients with pancreatic cancer have a poor prognosis, as pancreatic cancer is often diagnosed in late stage.
• The majority of patients with pancreatic cancer began their diagnostic process in general practice.
• General practitioners (GPs) suspected cancer at the first consultation in one out of three patients with pancreatic cancer; more often in older and comorbid patients.
• The GPs suspicion of cancer was associated with urgent referral and shorter time to diagnosis.

     

The East Africa Consortium for human papillomavirus and cervical cancer in women living with HIV/AIDS

The East Africa Consortium was formed to study the epidemiology of human papillomavirus (HPV) infections and cervical cancer and the influence of human immunodeficiency virus (HIV) infection on HPV and cervical cancer, and to encourage collaborations between researchers in North America and East African countries. To date, studies have led to a better understanding of the influence of HIV infection on the detection and persistence of oncogenic HPV, the effects of dietary aflatoxin on the persistence of HPV, the benefits of antiretroviral therapy on HPV persistence, and the differences in HPV detections among HIV-infected and HIV-uninfected women undergoing treatment for cervical dysplasia by either cryotherapy or LEEP. It will now be determined how HPV testing fits into cervical cancer screening programs in Kenya and Uganda, how aflatoxin influences immunological control of HIV, how HPV alters certain genes involved in the growth of tumours in HIV-infected women. Although there have been challenges in performing this research, with time, this work should help to reduce the burden of cervical cancer and other cancers related to HIV infection in people living in sub-Saharan Africa, as well as optimized processes to better facilitate research as well as patient autonomy and safety.

KEY MESSAGES

• The East Africa Consortium was formed to study the epidemiology of human papillomavirus (HPV) infections and cervical cancer and the influence of human immunodeficiency virus (HIV) infection on HPV and cervical cancer.
• Collaborations have been established between researchers in North America and East African countries for these studies.
• Studies have led to a better understanding of the influence of HIV infection on the detection and persistence of oncogenic HPV, the effects of dietary aflatoxin on HPV detection, the benefits of antiretroviral therapy on HPV persistence, and the differences in HPV detections among HIV-infected and HIV-uninfected women undergoing treatment for cervical dysplasia by either cryotherapy or LEEP.

     

Effect of immune checkpoint inhibitors in patients with gastric hepatoid adenocarcinoma: a case report and literature review

Gastric hepatoid adenocarcinoma (GHAC) is a highly aggressive histological subtype of gastric cancer (GC) with similar tissue morphology to hepatocellular carcinoma. GHAC frequently produces alpha-fetoprotein (AFP) and has a poor prognosis; however, standardized treatment remains elusive. We report a male patient in his early 60s with GHAC who received immunotherapy, and the curative effect was evaluated. He was admitted because of progressive fatigue and dizziness for 2 months. He had experienced spontaneous epigastric pain with muscular defense of the epigastrium and accompanying tenderness 1 year earlier and underwent radical gastrectomy. Immunohistochemistry showed that hepatocyte-specific marker (Hep) was highly-expressed, indicating probable GHAC. Additionally, imaging suggested GC recurrence or gastric stump cancer. Radioimmunoassay indicated an AFP level of >1210.00 µg/L, and liver biopsy was performed following abdominal contrast-enhanced computed tomography. Pathology showed a few hepatocytes and proliferative fibrous connective tissue. The patient received three cycles of chemotherapy, with no obvious improvement. The possibility of surgical treatment was excluded, and immunotherapy or palliative treatment was selected. He received 11 cycles of a programed death-1 (PD-1) monoclonal antibody, and the effect of treatment was satisfactory. The mechanism of action of immunotherapy in GHAC warrants further investigation.     

经肛门取出标本腹腔镜下直肠癌根治术14例

目的:总结经肛门取出标本腹腔镜下直肠癌根治术手术的体会。方法:分析经肛门取出标本腹腔镜直肠癌根治术14例的临床资料。结果:所有患者顺利完成手术,无严重并发症。术后5~8 d出院。随访3月~24个月,均无局部复发或远处转移。结论:经肛门取出标本腹腔镜直肠癌根治术创伤小、愈合快,可达到肿瘤治疗目的。     

宫颈癌筛查“三阶梯”方案的效果观察

目的: 观察宫颈癌筛查“三阶梯”方案在我院妇科阴道镜门诊就诊病人中的应用价值。方法: 选取
2012 － 10 ～ 2014 － 08 就诊于解放军总医院妇科阴道镜门诊的连续病人704 例,以组织病理学为诊断金标准,计
算液基细胞学、高危型人乳头状病毒( Human popilloma virus,HPV) 检测及阴道镜结果的诊断指标。结果: 随年
龄增加,TCT、Hr － HPV、阴道镜及病理阳性率有升高趋势,TCT 和阴道镜统计学检验有显著性差异。TCT 灵敏度
90． 24%,特异度17． 55%,诊断符合率42． 18%,Kappa = 0． 049; HPV 灵敏度95． 11%,特异度21． 28%,诊断符合率
55． 62%,Kappa = 0． 155; 阴道镜灵敏度83． 84%,特异度75． 27%,诊断符合率79． 26%,Kappa = 0． 587。结论: 宫颈
癌筛查“三阶梯”方案可以有效地发现宫颈病变的高危人群,但由于细胞学检查和HPV 检测的特异度较低,使阴
道镜门诊存在过度转诊的现象,阴道镜的诊断价值较高,是三阶梯方案中不可缺少的重要部分。     

Pilot study of intravesical instillation of two new generation anthracycline antibiotics in prevention of superficial bladder cancer recurrence

Background Superficial bladder cancer accounts for 60%-70% of all bladder cancer cases in China, when treatment consists of only transurethral resection of the bladder tumor （TUR-BT）, recurrence and progresses in the bladder are observed in some patients. There are numerous reports of trials of intravesical instillation of anticancer agents with the objective of lowering this recurrence rate. The aim of this study was to compare the prophylactic efficacy and safety of epirubicin （EPI）, pirarubicin （THP） and hydroxycamptothecin （HCPT） in superficial bladder cancer.Methods This study enrolled a total of 189 patients who had been diagnosed with superficial bladder cancer during the period from 2004 through 2007 at Beijing Friendship Hospital. All patients were randomly allocated to one of three treatment groups. Patients in group A received 29 doses of EPI 30 mg/30 ml, patients in group B received 29 doses of THP 30 mg/30 ml, and patients in group C received 29 doses of HCPT 30 mg/30 ml, over a period of 24 months.Results The recurrence-free rate in the 2 anthracycline treatment groups （A and B） were significantly better than that of the HCPT treatment group. In the safety evaluation, the incidences of pollakiuria, pain on urination, dysuria, hematuria,and contracted bladder were not significantly different between groups A and B, but some were significantly higher in groups A and B than that in group C.Conclusion The efficacy of EPI and THP was significantly better than HCPT in the prevention of bladder cancer recurrence.     

吉西他滨联合槲皮素对胰腺癌细胞Panc-1凋亡的影响研究

目的研究吉西他滨联合槲皮素抑制胰腺癌细胞Panc-1增殖,促进其凋亡的效果.方法设立槲皮素(终浓度为50μM)、吉西他滨(50μg/ml)、吉西他滨联合槲皮素和对照组4组,MTS法检测药物对Panc-1细胞凋亡的影响,流式细胞仪检测联合药物处理对细胞凋亡和细胞周期的影响,最后应用荧光定量PCR法测定凋亡相关基因BCL-2家族蛋白的相对表达.结果吉西他滨联合槲皮素后,对胰腺癌促凋亡效果增强,同时改变细胞周期,使其S期减少,BCL-2家族促凋亡基因表达上调.结论槲皮素能够显著增强吉西他滨抑制胰腺癌恶性增殖的作用.     

TrkC在乳腺癌中的表达及其临床意义

目的 探讨TrkC在乳腺癌中的表达及其临床意义.方法 收集1994～2006年住院接受根治手术的女性乳腺癌患者共100例,进行随访;收集同期接受手术的乳腺纤维腺瘤或乳腺增生症共30例.分3组:实验组为术后复发转移者共46例,对照组1为手术时间及发病年龄相近的术后未发生复发转移者共54例,对照组2为乳腺纤维腺瘤或乳腺增生症共30例.常规病理蜡块切片,应用免疫组织化学技术,检测TrkC在3组中的表达情况.结果 实验组TrkC的表达率均较对照组1、2高(P＜0.05);TNM分期越差,肿瘤越大,TrkC表达越强(均P＜0.05).结论 TrkC是乳腺癌根治手术后复发转移的危险因素;TrkC是评估乳腺癌术后预后的肿瘤标志物;TrkC有望成为乳腺癌生物靶向治疗的新靶点.