Helicobacter pylori associated chronic gastritis,clinical syndromes,precancerous lesions,and pathogenesis of gastric cancer development

Helicobacter pylori(H.pylori)infection is well known to be associated with the development of precancerous lesions such as chronic atrophic gastritis(AG),or gastric intestinal metaplasia(GIM),and cancer.Various molecular alterations are identified not only in gastric cancer(GC)but also in precancerous lesions.H.pylori treatment seems to improve AG and GIM,but still remains controversial.In contrast,many studies,including meta-analysis,show that H.pylori eradication reduces GC.Molecular markers detected by genetic and epigenetic alterations related to carcinogenesis reverse following H.pylori eradication.This indicates that these changes may be an important factor in the identification of high risk patients for cancer development.Patients who underwent endoscopic treatment of GC are at high risk for development of metachronous GC.A randomized controlled trial from Japan concluded that prophylactic eradication of H.pylori after endoscopic resection should be used to prevent the development of metachronous GC,but recent retrospective studies did not show the tendency.Patients with precancerous lesions(molecular alterations)that do not reverse after H.pylori treatment,represent the"point of no return"and may be at high risk for the development of GC.Therefore,earlier H.pylori eradication should be considered for preventing GC development prior to the appearance of precancerous lesions.

Androgen synthesis inhibitors in the treatment of castration-resistant prostate cancer

Suppression of gonadal testosterone synthesis represents the standard first line therapy for treatment of metastatic prostate cancer. However, in the majority of patients who develop castration-resistant prostate cancer （CRPC）, it is possible to detect persistent activation of the androgen receptor （AR） through androgens produced in the adrenal gland or within the tumor itself. Abiraterone acetate was developed as an irreversible inhibitor of the dual functional cytochrome P450 enzyme CYP17 with activity as a 17（^-hydroxylase and 17,20-1yase. CYP17 is necessary for production of nongonadal androgens from cholesterol. Regulatory approval of abiraterone in 2011, based on a phase III trial showing a significant improvement in overall survival （OS） with abiraterone and prednisone versus prednisone, represented proof of principle that targeting AR is essential for improving outcomes in men with CRPC. Inhibition of 17α-hydroxylase by abiraterone results in accumulation of upstream mineralocorticoids due to loss of cortisol-mediated suppression of pituitary adrenocorticotropic hormone （ACTH）, providing a rationale for development of CYP17 inhibitors with increased specificity for 17,20-1yase （orteronel, galeterone and VT-464） that can potentially be administered without exogenous corticosteroids. In this article, we review the development of abiraterone and other CYP17 inhibitors; recent studies with abiraterone that inform our understanding of clinical parameters such as drug effects on quality-of-life, potential early predictors of response, and optimal sequencing of abiraterone with respect to other agents; and results of translational studies providing insights into resistance mechanisms to CYP17 inhibitors leading to clinical trials with drug combinations designed to prolong abiraterone benefit or restore abiraterone activity.

Inhalation treatment of lung cancer: the influence of composition, size and shape of nanocarriers on their lung accumulation and retention

Objective: Various nanoparticles have been designed and tested in order to select optimal carriers for the inhalation delivery of anticancer drugs to the lungs. Methods: The following nanocarriers were studied: micelles, liposomes, mesoporous silica nanoparticles(MSNs), poly propyleneimine(PPI) dendrimer-siRNA complexes nanoparticles, quantum dots(QDs), and poly(ethylene glycol) polymers. All particles were characterized using the following methods: dynamic light scattering, zeta potential, atomic force microscopy, in vitro cyto- and genotoxicity. In vivo organ distribution of all nanoparticles, retention in the lungs, and anticancer effects of liposomes loaded with doxorubicin were examined in nude mice after the pulmonary or intravenous delivery. Results: Significant differences in lung uptake were found after the inhalation delivery of lipid-based and non-lipid-based nanoparticles. The accumulation of liposomes and micelles in lungs remained relatively high even 24 h after inhalation when compared with MSNs, QDs, and PPI dendrimers. There were notable differences between nanoparticle accumulation in the lungs and other organs 1 and 3 h after inhalation or intravenous administrations, but 24 h after intravenous injection all nanoparticles were mainly accumulated in the liver, kidneys, and spleen. Inhalation delivery of doxorubicin by liposomes significantly enhanced its anticancer effect and prevented severe adverse side effects of the treatment in mice bearing the orthotopic model of lung cancer.Conclusion: The results of the study demonstrate that lipid-based nanocarriers had considerably higher accumulation and longer retention time in the lungs when compared with non-lipid-based carriers after the inhalation delivery. These particles are most suitable for effective inhalation treatment of lung cancer.

Chemo/Dietary prevention of cancer:perspectives in China

Cancer is a major disease worldwide and different approaches are needed for its prevention.Previous laboratory and clinical studies suggest that cancer can be prevented by chemicals,including those from the diet.Furthermore,epidemiological studies have suggested that deficiencies in certain nutrients can increase the risk of some cancers.In this article on chemo/dietary prevention,examples will be given to illustrate the effectiveness of chemopreventive agents in the prevention of breast,colon and prostate cancers in high-risk populations and the possible side effects of these agents.The potential usefulness of dietary approaches in cancer prevention and the reasons for some of the failed trials will be discussed.Lessons learned from these studies can be used to design more relevant research projects and develop effective measures for cancer prevention in the future.The development of effective chemopreventive agents,the use of nutrient supplements in deficient or carcinogen-exposed populations,and the importance of cohort studies will be discussed in the context of the current socioeconomic situation in China.More discussions are needed on how we can influence society to pay more attention to cancer prevention research and measures.

Targeting mTOR network in colorectal cancer therapy

The mechanistic target of rapamycin(mTOR)integrates growth factor signals with cellular nutrient and energy levels and coordinates cell growth,proliferation and survival.A regulatory network with multiple feedback loops has evolved to ensure the exquisite regulation of cell growth and division.Colorectal cancer is the most intensively studied cancer because of its high incidence and mortality rate.Multiple genetic alterations are involved in colorectal carcinogenesis,including oncogenic Ras activation,phosphatidylinositol 3-kinase pathway hyperactivation,p 53 mutation,and dysregulation of wnt pathway.Many oncogenic pathways activate the mTOR pathway.mTOR has emerged as an effective target for colorectal cancer therapy.In vitro and preclinical studies targeting the mTOR pathway for colorectal cancer chemotherapy have provided promising perspectives.However,the overall objective response rates in major solid tumors achieved with single-agent rapalog therapy have been modest,especially in advanced metastatic colorectal cancer.Combination regimens of mTOR inhibitor with agents such as cytotoxic chemotherapy,inhibitors of vascular endothelial growth factor,epidermal growth factor receptor and Mitogen-activated protein kinase kinase(MEK)inhibitors are being intensively studied and appear to be promising.Further understanding of the molecular mechanism in mTOR signaling network is needed to develop optimized therapeutic regimens.In this paper,oncogenic gene alterations in colorectal cancer,as well as their interaction with the mTOR pathway,are systematically summarized.The most recent preclinical and clinical anticancer therapeutic endeavors are reviewed.New players in mTOR signaling pathway,such as nonsteroidal anti-inflammatory drug and metformin with therapeutic potentials are also discussed here.

Minimally manipulated autologous adherent bone marrow cells (ABMCs):a promising cell therapy of spinal cord injury

Spinal cord injury（SCI）is a devastating ailment that results in drastic life style alterations for the patients and their family members（Mc Donald and Sadowsky,2002）.Damage post injury causes necrosis,edema,hemorrhage and vasospasm.Post injury,secondary damage is caused by ischemia,

MicroRNA-371a-3p as a blood-based biomarker in testis cancer

MicroRNAs(miRNAs)are small noncoding RNAs involved in the regulation of mRNA transcription and translation,and possess all desirable features of an ideal tumor marker.Of almost 31 different miRNA clusters identified in germ cell tumors(GCTs),miR-371a-3p has shown exceptionally high sensitivity and specificity for both seminomatous and nonseminomatous GCTs.It is easily obtainable and correlates well with tumor burden.Recent multiinstitutional prospective studies have shown promising test characteristics for miR-371a-3p as a diagnostic blood-based biomarker for GCT prior to orchiectomy including 80%e100%sensitivity and 90%e100%specificity.This accuracy may address other unmet needs in the management of patients with GCT.Early studies have suggested the utility of miR-371a-3p in detecting occult nodal metastasis in high-risk clinical stage I and early stage II disease.Ongoing clinical trials including SWOG 1823 and AGCT1531 are specifically designed to confirm the utility of miR-371a-3p in clinical stage I GCT.Despite its strong association with viable GCT after treatment with chemotherapy,miR-371a-3p does not seem to accurately predict the presence of teratoma in residual lesions.Also,standardization of extraction and interpretation methods is a necessary step to assure uniform results across different institutions.

Offshore Training in Navy Personnel Is Associated with Uninvestigated Dyspepsia

To investigate the known and new factors associated with uninvestigated dyspepsia （UD）, we surveyed 8600 Chinese navy personnel with offshore training shorter than 1 month or longer than 9 months per year. All respondents were required to complete a questionnaire covering demographics, the Chinese version of the Rome Ⅲ survey, eating habits, life styles, and medical and family history. The response rate was 94.3% （8106/8600） with 4899 respondents qualified for analysis, including 1046 with offshore training and 3853 with onshore training. The prevalence of UD was higher in the offshore group than in the onshore group （12.6% vs. 6.9%, P〈0.001）, with a general prevalence of 8.1%. The subjects with offshore training were more likely to suffer from UD and postprandial distress syndrome （OR= 1.955 95% CI 1.568-2.439, P〈0.001 and OR=1.789, 95% CI 1.403-2.303, P〈0.001, respectively）. The mul- tivariate logistic regression analysis showed UD was associated with offshore training （OR=1.580, 95% CI 1.179-2.118, P=-0.002）, family history （OR=1.765, 95% CI 1.186-2.626, P=0.005） and smoking （OR=1.270, 95% CI 1.084-1.488, P=0.003）, but not with alcohol drinking. The association between dysentery history and UD was undetermined/borderline （P=0.056-0.069）. In conclusion, we identified offshore training as a new factor associated with UD, and also confirmed 2 known associated factors, family history and smoking.

Hepatic pseudotumor associated with Strongyloides infection:A case report

BACKGROUND Strongyloides sterocoralis is a parasitic infection caused by a roundworm that is transmitted through soil contaminated with larvae.It can infrequently cause hepatic abscesses in immunocompromised patients and is rarely reported to form hepatic lesions in immunocompetent hosts.CASE SUMMARY We present a case study of a 45-year-old female who presented with right upper quadrant abdominal pain and constitutional symptoms for several weeks.Crosssectional imaging identified several malignant-appearing liver masses.Further investigation,including serological testing and histopathologic examination,revealed the presence of serum Strongyloides antibodies and hepatic granulomas with extensive necrosis.Following treatment with ivermectin for 2 wk,there was complete resolution of the liver lesions and associated symptoms.CONCLUSION This case highlights the importance of considering parasitic infections,such as Strongyloides,in the differential diagnosis of hepatic masses.Early recognition and appropriate treatment can lead to a favorable outcome and prevent unnecessary invasive procedures.Increased awareness among clinicians is crucial to ensure the timely diagnosis and management of such cases.

乌苏酸联合吉西他滨对胰腺癌PANC-1细胞增殖和凋亡的影响

目的:探讨乌苏酸联合吉西他滨对胰腺癌PANC-1细胞增殖和凋亡的影响。方法:以乌苏酸、吉西他滨单独用药作用于体外培养的胰腺癌细胞PANC-1细胞,采用细MTT法检测细胞半抑制浓度(IC_(50)),确定药物给药浓度;以乌苏酸(2μmol/L)、吉西他滨(0.2μmol/L)单独及联合作用于PANC-1细胞,采用锥虫蓝染色法检测PANC-1细胞存活率,PI染色后PANC-1细胞中检测细胞凋亡,采用细胞划痕实验检测PANC-1细胞迁移和伤口愈合情况,采用Western blotting检测对照组、乌苏酸组与吉西他滨组单独及联合用药组细胞中P-JNK、Bcl-2、IL-6、P-Stat 3、NF-κB和Cox-2蛋白的表达。结果:乌苏酸和吉西他滨对胰腺癌PANC-1细胞均有较强的抑制作用,其IC_(50)分别是13.67和2.78μmol/L,据此选择它们的实验浓度分别为2和0.2μmol/L。两者联合用药比分别单独用药能更显著抑制癌细胞的增殖活性[(46.47±5.07)%vs(78.38±8.65)%、(76.12±3.23)%,均P<0.05],能更明显诱导癌细胞凋亡[(39.78±7.01)%vs(20.35±8.51)%、(20.35±8.51)%,均P<0.01]和抑制细胞迁移能力(P<0.01),同时更显著抑制凋亡相关蛋白Bcl-2、IL-6的表达及促进P-JNK的表达。结论:乌苏酸和吉西他滨协同增强抑制胰腺癌PANC-1细胞的增殖和迁移以及促凋亡作用,其机制可能与抑制Bcl-2、IL-6、P-Stat 3和促进P-JNK蛋白表达有关。

绿原酸联合吉西他滨对胰腺癌细胞增殖和凋亡的影响

目的:探讨绿原酸联合吉西他滨对胰腺癌PANC-1细胞增殖和凋亡的影响。方法:以绿原酸、吉西他滨单独用药作用于体外培养的PANC-1细胞,采用细胞毒实验(MTT)法检测细胞半抑制浓度(IC50),确定药物给药浓度;以绿原酸(3μmol/L)、吉西他滨(0.2μmol/L)单独及联合作用于PANC-1细胞,采用台盼蓝染色法检测细胞存活率,PI染色检测细胞凋亡;采用细胞划痕实验检测细胞迁移能力;采用Western blot检测P-JNK、Bcl-2、IL-6、PSTAT3、NF-κB、COX-2蛋白表达。结果:与对照组比较,联合用药组的细胞凋亡率显著升高,存活率显著降低(P<0.01)。细胞划痕实验表明,联合用药组细胞迁移能力显著低于对照组(P<0.01)。Western blot结果表明,联合用药组显著下调COX-2、Bcl-2、IL-6、P-STAT3蛋白的表达,上调P-JNK蛋白表达(P<0.05或P<0.01)。结论:绿原酸和吉西他滨联合应用能增强对胰腺癌细胞系PANC-1的增殖抑制和促凋亡作用。

Gain-of-function mutant p53 in cancer progression and therapy

p53 is a key tumor suppressor,and loss of p53 function is frequently a prerequisite for cancer development.The p53 gene is the most frequently mutated gene in human cancers;p53 mutations occur in>50%of all human cancers and in almost every type of human cancers.Most of p53 mutations in cancers are missense mutations,which produce the full-length mutant p53(mutp53)protein with only one amino acid difference from wild-type p53 protein.In addition to loss of the tumor-suppressive function of wild-type p53,many mutp53 proteins acquire new oncogenic activities independently of wild-type p53 to promote cancer progression,termed gain-of-function(GOF).Mutp53 protein often accumulates to very high levels in cancer cells,which is critical for its GOF.Given the high mutation frequency of the p53 gene and the GOF activities of mutp53 in cancer,therapies targeting mutp53 have attracted great interest.Further understanding the mechanisms underlying mutp53 protein accumulation and GOF will help develop effective therapies treating human cancers containing mutp53.In this review,we summarize the recent advances in the studies on mutp53 regulation and GOF as well as therapies targeting mutp53 in human cancers.

Toward point-of-care assessment of patient response:a portable tool for rapidly assessing cancer drug efficacy using multifrequency impedance cytometry and supervised machine learning

We present a novel method to rapidly assess drug efficacy in targeted cancer therapy,where antineoplastic agents are conjugated to antibodies targeting surface markers on tumor cells.We have fabricated and characterized a device capable of rapidly assessing tumor cell sensitivity to drugs using multifrequency impedance spectroscopy in combination with supervised machine learning for enhanced classification accuracy.Currently commercially available devices for the automated analysis of cell viability are based on staining,which fundamentally limits the subsequent characterization of these cells as well as downstream molecular analysis.Our approach requires as little as 20μL of volume and avoids staining allowing for further downstream molecular analysis.To the best of our knowledge,this manuscript presents the first comprehensive attempt to using high-dimensional data and supervised machine learning,particularly phase change spectra obtained from multi-frequency impedance cytometry as features for the support vector machine classifier,to assess viability of cells without staining or labelling.

Combination drug regimens for metastatic clear cell renal cell carcinoma

Renal cell carcinomas(RCC)make up about 90%of kidney cancers,of which 80%are of the clear cell subtype.About 20%of patients are already metastatic at the time of diagnosis.Initial treatment is often cytoreductive nephrectomy,but systemic therapy is required for advanced RCC.Single agent targeted therapies are moderately toxic and only somewhat effective,leading to development of immunotherapies and combination therapies.This review identifies limitations of monotherapies for metastatic renal cell carcinoma,discusses recent advances in combination therapies,and highlights therapeutic options under development.The goal behind combining various modalities of systemic therapy is to potentiate a synergistic antitumor effect.However,combining targeted therapies may cause increased toxicity.The initial attempts to create therapeutic combinations based on inhibition of the vascular endothelial growth factor or mammalian target of rapamycin pathways were largely unsuccessful in achieving a profile of increased synergy without increased toxicity.To date,five combination therapies have been approved by the U.S.Food and Drug Administration,with the most recently approved therapies being a combination of checkpoint inhibition plus targeted therapy.Several other combination therapies are under development,including some in the phase 3 stage.The new wave of combination therapies for metastatic RCC has the potential to increase response rates and improve survival outcomes while maintaining tolerable side effect profiles.

Potential therapeutic effect of epigenetic therapy on Ireatment-induced neuroendocrine prostate cancer

Although adenocarcinomas of the prostate are relatively indolent, some patients with advanced adenocarcinomas show recurrence of treatment-induced neuroendocrine prostate cancer, which is highly aggressive and lethal. Detailed biological features of treatment-induced neuroendocrine prostate cancer have not been characterized owing to limited biopsies/resections and the lack of a cellular model. In this study, we used a unique cellular model （LNCaP/NE1.8） to investigate the potential role of cancer stem cells in treatment-induced neuroendocrine prostate cancer with acquired resistance to hormonal therapy and chemotherapy. We also studied the role of cancer stem cells in enhancing invasion in treatment-induced neuroendocrine prostate cancer cells that recurred after long-term androgen-ablation treatment. Using an in vitro system mimicking clinical androgen-ablation, our results showed that the neuroendocrine-like subclone NE1.8 cells were enriched with cancer stem cells. Compared to parental prostate adenocarcinoma LNCaP cells, NE1.8 cells are more resistant to androgen deprivation therapy and chemotherapeutic agents and show increased cancer cell invasiveness. Results from this study also suggest a potential epigenetic therapeutic strategy using suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, as a chemotherapeutic agent for therapy-resistant treatment-induced neuroendocrine prostate cancer cells to minimize the risk of prostate cancer recurrence and metastasis.

帕金森病相关蛋白Parkin:癌症中一个不同寻常的角色

Parkin基因的突变可引起家族性帕金森病。越来越多的证据表明,Parkin也可作为肿瘤抑制因子来发挥功能。Parkin是一种E3泛素连接酶,在与肿瘤发生相关的各种细胞过程中起到重要的作用,包括细胞周期、细胞增殖、凋亡、转移、线粒体自噬和代谢重编程。在此,我们对Parkin在癌症中的作用和机制进行综述。

Radiation Oncology and Medical Devices(Part 2)

Radiation oncology is one of the three major treatment modalities to manage cancer patient cares,and is a discipline mainly driven by technology and medical devices.Modern radiation treatments have become fairly complex and involve in utilizing a variety of medical devices to achieve the goal of providing conformal radiation dose coverage to the tumor target(s)while maximizing the sparing of normal organ structures.Recently,different forms of linear accelerators/radioactive source based machines have been invented and developed with the aim of providing improved treatments and more treatment options.Besides linear accelerators(Linac)that have been undergoing constant improvement and advancement and can deliver fairly complicated dose distribution patterns,imaging systems,computer information and calculation systems have been more and more integrated into radiotherapy processes.To bring radiotherapy to a potentially higher level,many institutions have either acquired or started to consider particle therapy,especially proton therapy.The complexity of modern radiotherapy demands in-depth understanding of radiation physics and machine engineering as well as computer information systems.This paper is intended to provide an introductory description of radiation oncology and related procedures,and to provide an overview of the current status of medical devices in radiotherapy in the United States of America.This paper covers the radiation delivery systems,imaging systems,treatment planning systems,record and verify systems,and QA systems.

Radiation Oncology and Medical Devices( Part 1)

Modern radiation treatments have become fairly complex and involve in utilizing a variety of medical devices to achieve the goal of providing conformal radiation dose coverage to the tumor target(s)while maximizing the sparing of normal organ structures.Recently,different forms of linear accelerators/radioactive source based machines have been invented and developed with the aim of providing improved treatments and more treatment options.Besides linear accelerators(Linac)that have been undergoing constant improvement and advancement and can deliver fairly complicated dose distribution patterns,imaging systems,computer information and calculation systems have been more and more integrated into radiotherapy processes.To bring radiotherapy to a potentially higher level,many institutions have either acquired or started to consider particle therapy,especially proton therapy.The complexity of modern radiotherapy demands in-depth understanding of radiation physics and machine engineering as well as computer information systems.This paper is intended to provide an introductory description of radiation oncology and related procedures,and to provide an overview of the current status of medical devices in radiotherapy in the United States of America.This paper covers the radiation delivery systems,imaging systems,treatment planning systems,record and verify systems,and QA systems.

Mechanism-directed combinational immunotherapies in liver cancer hold promise

Hepatocellular carcinoma(HCC)is the most prevalent form of primary liver cancer,and it is the third leading cause of cancer-related mortality worldwide.The primary causes of HCC include chronic infections with hepatitis B virus(HBV)or hepatitis C virus(HCV)and alcoholic steatohepatitis(ASH)or nonalcoholic steatohepatitis(NASH).

Risk of complications and urinary incontinence following cytoreductive prostatectomy： a multi-institutional study

Emerging evidence has suggested that cytoreductive prostatectomy （CRP） allows superior oncologic control when compared to current standard of care androgen deprivation therapy alone. However, the safety and benefit of cytoreduction in metastatic prostate cancer （mPCa） has not been proven. Therefore, we evaluated the incidence of complications following CRP in men newly diagnosed with mPCa. A total of 68 patients who underwent CRP from 2006 to 2014 at four tertiary surgical centers were compared to 598 men who underwent radical prostatectomy for clinically localized prostate cancer （PCa）. Urinary incontinence was defined as the use of any pad. CRP had longer operative times （200 min vs 140 min, P 〈 0.0001） and higher estimated blood loss （250 ml vs 125 ml, P 〈 0.0001） compared to the control group. However, both overall （8.82% vs 5.85%） and major complication rates （4.41% vs 2.17%） were comparable between the two groups. Importantly, urinary incontinence rate at 1-year after surgery was significantly higher in the CRP group （57.4% vs 90.8%, P 〈 0.0001）. Univariate logistic analysis showed that the estimated blood loss was the only independent predictor of perioperative complications both in the unadjusted model （OR： 1.18; 95% Ch 1.02-1.37; P= 0.025） and surgery type-adjusted model （OR： 1.17; 95% Ch 1.01-1.36; P= 0.034）. In conclusion, CRP is more challenging than radical prostatectomy and associated with a notably higher incidence of urinary incontinence. Nevertheless, CRP is a technically feasible and safe surgery for selecting PCa patients who present with node-positive or bony metastasis when performed by experienced surgeons. A prospective, multi-institutional clinical trial is currently underway to verify this concept.