Enhanced proliferation,invasion,and epithelial-mesenchymal transition of nicotine-promoted gastric cancer by periostin

AIM:To investigate the contribution of periostin in nicotine-promoted gastric cancer cell proliferation,survival,invasion,drug resistance,and epithelial-mesenchymal transition(EMT).METHODS:Gastric cancer cells were treated with nicotine and periostin protein expression was determined by immunoblotting.Periostin mRNA in gastric cancer cells was silenced using small interfering RNA(siRNA) techniques and periostin gene expression was evaluated by quantitative reverse transcription-polymerase chain reaction.Gastric cancer cells transfected with control or periostin siRNA plasmid were compared in terms of cell proliferation using the methylthiazolyldiphenyl-tetrazolium bromide assay.Cell apoptosis was compared using annexin V-fluoresceine isothiocyanate and propidium iodine double staining.Tumor invasion was determined using the Boyden chamber invasion assay,and the EMT marker Snail expression was evaluated by immunoblotting.RESULTS:Nicotine upregulated periostin in gastric cancer cells through a COX-2 dependent pathway,which was blocked by the COX-2-specific inhibitor NS398.Periostin mRNA expression was decreased by ～87.2% by siRNA in gastric cancer cells,and stable periostinsilenced cells were obtained by G418 screening.Periostin-silenced gastric cancer cells exhibited reduced cell proliferation,elevated sensitivity to chemotherapy with 5-fluorouracil,and decreased cell invasion and Snail expression(P < 0.05).CONCLUSION:Periostin is a nicotine target gene in gastric cancer and plays a role in gastric cancer cell growth,invasion,drug resistance,and EMT facilitated by nicotine.

Heat shock protein 70 chaperoned alpha-fetoprotein in human hepatocellular carcinoma cell line BEL-7402

AIM: To investigate the interaction between heat shock protein 70 (HSP70) and α-fetoprotein (AFP) in human hepatocellular carcinoma (HCC) cell line BEL7402.METHODS: The expression and localization of HSP70 and AFP in human HCC cell line BEL-7402 were determined by immunocytochemistry and indirect immunofluorescence cytochemical staining. The interaction between HSP70 and AFP in HCC cells was analyzed by immunoprecipitation and Western blot.RESULTS: Immunocytochemical staining detection showed that HCC cell BEL-7402 expressed a high level of HSP70 and AFP synchronously. Both were stained in cell plasma.AFP existed in the immunoprecipitate of anti-HSP70 mAb,while there was HSP70 in the immunoprecipitate of antiAFP mAb.CONCLUSION: HSP70 chaperones AFP in human HCCcell BEL-7402. The interaction between HSP70 and AFP in human HCC cell can be a new route to study the pathogenesis and immunotherapy of HCC.

Metaplastic carcinoma of the right breast and simultaneous giant ovarian teratoma:a case report

We describe here a female patient who presented with a breast mass and giant abdominal mass.Fine needle aspiration cytology of the breast mass and histological examination after modified radical mastectomy confirmed metaplastic carcinoma of the breast.The epithelial components were formed by infiltrating ductal carcinoma with poor differentiation,and the sarcomatous components were formed by fibrosarcoma and osteosarcoma.Histological examination of the abdominal mass confirmed ovarian teratoma.The patient underwent modified radical mastectomy of the right breast and laparoscopic excision of the abdominal mass in the lower right quadrant.Having underwent six courses of chemotherapy,the patient is now in her tenth month after surgery and under follow-up,and she has no relapsed disease.These two diseases have never seen in one patient before.The case we report here provides some new data for research and clinical experience and it may also provide a new insight into the relationship between metaplastic breast carcinoma and ovarian teratoma.

Pathophysiology transforms to pathobiology:new technologies and interdisciplinary project-oriented learning

Integrative role of pathophysiology in medicine is analogous to that of systemic biology among non-medical life sciences. Pathology rooted in morphology,because autopsy and microscopy in early 19th century revealed some loci and elements of disease. However,this was not enough for comprehension of systemic disorders and relations between elements. This promoted the involvement of physiology and birth of pathophysiology. For a long time the methodological options for bedside studies were scarce,so generations of physicians percepted pathophysiology as a science of lab and vivarium only,unlike pathomorphology,had integrated in clinics earlier. This lead to fornication between two sister branches of pathology and teaching of pathology and clinical subjects separated. Methodological progress of 20th century created basis for less or non-invasive patient studies. Current advances of pathochemistry,medical genetics,immunopathology,bioinformatics-give the chance to pathophysiology and pathomorphology spread far beyond the constraint of their historical names and intermingle. Current Pathophysiology grew into clinics (via laboratory and functional diagnosis,which contains clinical experimenting). This promotes re-integration of pathology sister branches,not via absorption,but through mutual shift to clinical correlations. Holistic approach to patient,disease and education is traditional for Russian medicine. In our pathophysiology teaching,classical lab experiments are joint to early start of clinical pathology (6th term),case history analysis,lectures co-delivered by pathologist and clinician with demonstration of patients. Pathomorphologist and clinician are included in state board for pathophysiology exam. In teaching posters pathophysiological,clinical and pathomorphological data are fused. Local net of digital television microscopes gives instant video archive of experimental results added to student's protocols of lab studies. Teaching posters and course papers are contributed from student's data for project-oriented learning.

Phenotypic Classification of Well-Differentiated Gastric Adenocarcinoma

Objective： To investigate the genotypes of well-differentiated non-cardiac gastric adenocarcinoma and their clinicopathological significance. Methods： Sixty-four cases of well-differentiated non-cardiac gastric adenocarcinoma were included in this study. The expressions of intestinal phenotypic markers including CDX2, MUC2, Li-cadherin, CD10, Hepatocyte（Hep） and Villin, and gastric phenotypic markers including MUC5AC and pS2 were detected immunohistochemically. Based on the expressions of phenotypic markers, 64 cases can be divided into four phenotypes. Cases only expressing intestinal phenotypic markers were classified as intestinal phenotype; cases only expressing gastric phenotypic markers as gastric phenotype; cases expressing both intestinal and gastric phenotypic markers as gastrointestinal phenotype; and cases expressing neither intestinal nor gastric phenotypic marker as null phenotype. The association of phenotype and clinic-pathological parameters was analyzed. We also detected the expressions of markers related to the development and progression of cancer, including Rb, P53, c-Met, MIF, TGF-β-RII, β-catenin, CD44v6 and E-cadherin. Results： Of 64 cases, 33（51.6%） were intestinal type, 3（4.7%） were gastric type, 25（39.1%） were gastrointestinal type and 3（4.7%） were null type. Fifty-eight cases were either intestinal or gastrointestinal type, which accounted for 90.6% of all the cases. In addition, there was an association between phenotype and biological behaviors （invasion or metastasis）. The biological behaviors of intestinal and gastrointestinal type were better than gastric type. Compared with intestinal, gastric and gastrointestinal types, the biological behaviors of null type were the most aggressive. The biological behaviors of gastric carcinoma tended to be better as the number of expression of intestinal markers increased. Expression of markers related to the development and progression of cancer was not significantly correlated with phenotypes and biological behaviors of well-differentiated gastric carcinoma. Conclusion： Well-differentiated gastric adenocarcinomas are heterogeneous phenotypically. They can be divided into four phenotypes, namely intestinal, gastric, gastrointestinal and null types. Present findings show that well-differentiated gastric adenocarcinoma in the WHO classification is highly consistent with intestinal type gastric cancer in the Lauren classification. Expression of phenotypic marker is of certain clinic-pathologic significance.

Targeting EZH1/2 induces cell cycle arrest and inhibits cell proliferation through reactivation of p57CDKN1C and TP53INP1 in mantle cell lymphoma

Objective: To explore the effect of dysregulation of epigenetic regulator EZH1 and EZH2 on the proliferation in MCL and the underlying mechanisms.Methods: In this study, we elucidated the role of EZH1 and EZH2 overexpression by immunohistochemistry and correlated them to clinical outcome in 41 MCL patients.Quantitative real-time PCR and Western blot were applied to confirm the level of EZH1 and EZH2 in well-characterized MCL cell lines which were compared to those of na?ve B cells.Then we manipulated the expression of EZH1 and EZH2 in MCL cells using CRISPR/Cas9 system to directly investigate their functional roles in MCL.We also evaluated the effect of two small molecule selective inhibitors, EPZ005687 and UNC1999, on MCL cell proliferation, cell cycle distribution and apoptosis in vitro.Finally, we performed RNA-sequencing(RNA-Seq) and Chromatin immunoprecipitation(ChIP) assay to further gain insight into the underlying molecular mechanisms.Results: We found that EZH2 protein is overexpressed in approximately half of this cohort of MCL cases.More importantly, the overexpression of EZH2 is associated with poor OS in the patients.Nevertheless, simple EZH2 depletion in vitro has little impact on the viability of MCL cells, predominantly because of the consequent up-regulation of EZH1.Consistently, UNC1999, a dual EZH1/2 inhibitor, unlike the EZH2 selective inhibitor EPZ005687, exerts a potent inhibitory effect on MCL cells.Furthermore, we discover CDKN1C and TP53 INP1 as the two important cell cycle regulators, the expression of which are repressed by EZH1/2 mediated epigenetic regulation and are restored by EZH1/2 dual inhibition.Conclusions: Our study suggests that EZH2 participates in the pathogenesis of MCL which may serve as a potential biomarker for prognosis prediction.The dual inhibition of EZH1/2 is a promising therapeutic strategy for MCL.

Pathologic and molecular features of hepatocellular carcinoma:An update

Morphological diversity and several new distinct pathologic subtypes of hepatocellular carcinoma(HCC)are now well-recognized.Recent advances in tumor genomics and transcriptomics have identified several recurrent somatic/genetic alterations that are closely related with histomorphological subtypes and have therefore,greatly improved our understanding of HCC pathogenesis.Pathologic subtyping allows for a diagnosis which is clinically helpful and can have important implication in patient prognostication as some of these subtypes are extremely aggressive with vascular invasion,early recurrence,and worst outcomes.Several targeted treatments are now being considered in HCC,and the reporting of subtypes may be quite useful for personalized therapeutic purpose.This manuscript reviews the recently identified histomorphological subtypes and molecular alterations in HCC.

Effect of Intermittent Androgen Blockade on the Quality of Life of Patients with Advanced Prostate Carcinoma

OBJECTIVE To investigate the effect of intermittent androgen blockade (IAB)on the quality of life(QOL)of patients with advanced prostatic carcinoma(APC). METHODS Investigations on the QOL of 51 APC patients receiving IAB treatment,totaling 3 times,i.e.6 months before and after,and 12 months after treatment,were perform using the EORTC QLQ-C30 measuring scale and QLQ-PR25 scale. RESULTS Although IAB became an economic burden for the families,it was lessened during the intermission(P<0.05).The overall health status significantly improved 6 months after IAB treatment(P<0.01),especially during the intermission(P<0.05),with a total or local easement of pain(P<0.01)and an improvement of urinary function(P<0.01).Although there was impairment, to various degrees,in many functions of the patients on the 6th month of treatment,such as the physical function(P<0.05),role function(P<0.05),the emotional(P<0.01)and the social functions(P<0.01),with an enhancement of fatigue(P<0.01),these functions gradual y recovered by the 12th month as the intermission started.Treatment-related symptoms such as flushing and mammary swel ing significantly emerged on the 6th treatment month (P<0.01),and lessened on the 12th(P<0.01).During the treatment period, there was an notable drop in sexual interest(P<0.01),with a deprivation of sex life,but revived to various degrees during the intermission(P<0.01). CONCLUSION Although IAB treatment of APC patients did impair the physiologic and psychologic status of patients to varying degrees,these were improved and restored during the intermission.

抗茵药物敏感性试验折点的解读与应用

抗菌药物敏感性试验是指导临床医生正确使用抗菌药物的重要工具。正确理解和运用药敏试验结果要求临床医生和临床微生物工作者具备药敏试验和药敏折点的相关知识，并能使用药代动力学／药效学原理优化抗菌药物治疗。（中华检验医学杂志，2013，36：289-291）

新近认识的肾细胞癌

肾细胞癌是一组起源于不同节段肾小管上皮细胞的恶性肿瘤，无论是组织形态学、免疫表型和分子遗传学特征，还是生物学行为方面都具有明显的异质性。在过去的20多年中，肾细胞癌的组织学分类经历了多次演进。

130例骨髓增生异常综合征（难治性血细胞减少）和获得性再生障碍性贫血患儿的临床及病理特征分析

目的 探讨儿童难治性血细胞减少（RCC）和获得性再生障碍性贫血（AAA）的临床特征和病理特征,为更好地诊断、鉴别诊断及治疗两种疾病患儿提供理论依据.方法 以130例RCC或AAA患儿为研究对象,回顾性分析其临床资料及骨髓活检病理特征.结果 130例患儿中78例（60.0％）为RCC,52例（40.0％）为AAA.RCC组患儿的外周血白细胞计数、中性粒细胞绝对值计数、血小板计数、血红蛋白、网织红细胞计数均显著高于AAA组（P＜0.01）.RCC组患儿骨髓活检示增生低下,84.6％（66/78）的患儿骨髓造血细胞比例介于20％～ 60％,98.7％ （77/78）的患儿造血细胞呈典型的“不均匀片状”分布、红系造血细胞簇状分布伴核左移,61.5％（48/78）的患儿可见小巨核细胞.AAA组患儿骨髓活检示增生极为低下,88.5％（46/52）的患儿骨髓造血细胞比例＜5％,98.1％（51/52）的患儿骨髓中未见巨核细胞.给予环孢素±兔-抗胸腺细胞球蛋白±雄激素±中药的免疫抑制方案治疗,RCC和AAA患儿3个月总有效率分别为59.5％和26.9％ （P=0.011）,6个月总有效率为75.0％和38.1％（P=0.007）.结论 RCC患儿外周血细胞减少及骨髓增生减低程度较AAA轻,其骨髓造血细胞呈“不均匀片状”分布、红系造血细胞簇状分布伴核左移及小巨核细胞的出现为鉴别于AAA的典型病理学特征.RCC和AAA患儿接受免疫抑制方案治疗均可获得确切疗效,但RCC患儿的总有效率较AAA高.

Pulmonary artery intimal sarcoma diagnosed by percutaneous transcatheter aspiration

Pulmonary artery intimal sarcoma （PALS） is a very rare but lethal disease, firstly described by Mandelstarnmin 1923.1 Since then, less than 300 cases have been reported worldwide. Due to similar clinical presentations, it is very difficult to distinguish with pulmonary thromboembolism （PTE）, leading to inappropriate treatments such as anticoagulation and thrombolysis.2-5Although with improvement of imaging modalities, the diagnosis of PAIS is still based on pathological examination, and the majority of specimens are taken by surgery or autopsy.

A case of tubulopapillary hidradenoma on the face

To the editor： In September 2013 ur department with a lesion on a 60-year-old man presented to left face. The lesion was found about one year ago without previous trauma or any other reasons, and enlarged slowly accompanying occasional itch. The medical and family histories were unremarkable. On dermatological examination, a solitary red-brown colored, firm, non-tender, mobile nodule of 0.8 cm diameter was seen on the left face. The surface of the nodule was smooth （Figure IA）. Provisional diagnoses of fibroma or sebaceous cyst were made. The lesion was excised and sent for histopathological examination.

Rapid local recurrence of an extraventricular neurocytoma that had disappeared after gamma knife radiosurgery

Central neurocytoma （CN）, first described by Hassoun et al in 1982, is a rare neuronal tumor of the centralnervous system, and accounts for 0.25%-0.5% of all intracranial tumors. CN commonly occurs as an intraventricular mass but may also occur as a periventricular parenchymal mass or even in locations remote from the ventricles, in which case it is termed as an extraventricular neurocytoma （EVN） （cerebral）. EVNs show a wide variability with regard to morphologic features, cellularity, and proliferation rate and are more frequently associated with poorer clinical outcomes than CNs. 1 To our knowledge, little is known regarding the treatment of atypical neurocytomas.

Lupus at the molecular level

Systemic lupus erythematosus(SLE)is a debilitating multi-factorial autoimmune disease(Shlomchik et al.,2001;La Cava,2009;Perry et al.,2011).It involves multiple organ systems with tissue damage driven by the activation of auto-reactive Tand B cells(Bruns et al.,2000;Langer et al.,2007).It can exist for years before being diagnosed and is known to be more common in women than in men.Intense research efforts have uncovered a complex lupus pathogenesis,many aspects of which are not very clear(Perry et al.,2011).