Metabologenomics and network pharmacology to understand the molecular mechanism of cancer research

In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of Clinical Cases 2023 November 6;11(31):7593-7609.Almost all living forms are able to manufacture particular chemicals-metabolites that enable them to differentiate themselves from one another and to overcome the unique obstacles they encounter in their natural habitats.Numerous methods for chemical warfare,communication,nutrition acquisition,and stress prevention are made possible by these specialized metabolites.Metabolomics is a popular technique for collecting direct mea-surements of metabolic activity from many biological systems.However,con-fusing metabolite identification is a typical issue,and biochemical interpretation is frequently constrained by imprecise and erroneous genome-based estimates of enzyme activity.Metabolite annotation and gene integration uses a biochemical reaction network to obtain a metabolite-gene association so called metabologe-nomics.This network uses an approach that emphasizes metabolite-gene consensus via biochemical processes.Combining metabolomics and genomics data is beneficial.Furthermore,computer networking proposes that using meta-bolomics data may improve annotations in sequenced species and provide testable hypotheses for specific biochemical processes.CONCLUSION The genome and metabolites of biological organisms are not fully characterized with current technologies.However,increasing high-throughput metabolomics and genomics data provide promising generation of paired data sets to understand the molecular mechanism of biochemical processes as well as determining targets for pharmaceutical drug design.Contemporary network infrastructures to integrate omics analysis can provide molecular mechanism of biochemical pathways.Furthermore,clinical data may be integrated to gene expression–metabolite expression by system genetics approach.Calculating pair-wise correlations and weighted correlation network analysis provide the basis of this integration[11-13].The occurrence of strong correlations between classified metabolites and co-expression transcripts implies either various roles of metabolites or linkages between metabolic pathways and the immune system.

Metabolomics for the diagnosis of bladder cancer: A systematic review

Objective: Metabolomics has been extensively utilized in bladder cancer (BCa) research, employing mass spectrometry and nuclear magnetic resonance spectroscopy to compare various variables (tissues, serum, blood, and urine). This study aimed to identify potential biomarkers for early BCa diagnosis.Methods: A search strategy was designed to identify clinical trials, descriptive and analytical observational studies from databases such as Medline, Embase, Cochrane Central Register of Controlled Trials, and Latin American and Caribbean Literature in Health Sciences. Inclusion criteria comprised studies involving BCa tissue, serum, blood, or urine profiling using widely adopted metabolomics techniques like mass spectrometry and nuclear magnetic resonance. Primary outcomes included description of metabolites and metabolomics profiling in BCa patients and the association of metabolites and metabolomics profiling with BCa diagnosis compared to control patients. The risk of bias was assessed using the Quality Assessment of Studies of Diagnostic Accuracy.Results: The search strategy yielded 2832 studies, of which 30 case-control studies were included. Urine was predominantly used as the primary sample for metabolite identification. Risk of bias was often unclear inpatient selection, blinding of the index test, and reference standard assessment, but no applicability concerns were observed. Metabolites and metabolomics profiles associated with BCa diagnosis were identified in glucose, amino acids, nucleotides, lipids, and aldehydes metabolism.Conclusion: The identified metabolites in urine included citric acid, valine, tryptophan, taurine, aspartic acid, uridine, ribose, phosphocholine, and carnitine. Tissue samples exhibited elevated levels of lactic acid, amino acids, and lipids. Consistent findings across tissue, urine, and serum samples revealed downregulation of citric acid and upregulation of lactic acid, valine, tryptophan, taurine, glutamine, aspartic acid, uridine, ribose, and phosphocholine.

Sternocleidomastoid flap for reconstruction of tongue small cell carcinoma: A case report

BACKGROUND The management of tongue carcinoma is excision and radical neck dissection followed with reconstruction.This is a case report of a patient with tongue squamous cell carcinoma(SCC)who underwent the procedure with sternocleidomastoid(SCM)flap reconstruction.CASE SUMMARY A 52-year-old woman without smoking history complained tongue ulcer since 3 years ago.Based on the histopathological examination,the patient was diagnosed with T2N2M0 right tongue SCC and underwent wide excision of tumor;right mandibular;neck dissection and were reconstructed with SCM flap.CONCLUSION SCC of the tongue requires wide excision and dissection of the neck and mandible if infiltration into the surrounding lymph nodes has been found.The SCM flap reconstruction could be used post-surgery.

Esophageal cancer management controversies: Radiation oncology point of view

Esophageal cancer treatment has evolved from single modality to trimodality therapy.There are some controversies of the role,target volumes and dose of radiotherapy(RT)in the literature over decades.The present review focuses primarily on RT as part of the treatment modalities,and highlight on the RT volume and its dose in the management of esophageal cancer.The randomized adjuvant chemoradiation(CRT)trial,intergroup trial(INT 0116)enrolled 559 patients with resected adenocarcinoma of the stomach or gastroesophageal junction.They were randomly assigned to surgery plus postoperative CRT or surgery alone.Analyses show robust treatment benefit of adjuvant CRT in most subsets for postoperative CRT.The Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study(CROSS)used a lower RT dose of41.4 Gray in 23 fractions with newer chemotherapeutic agents carboplatin and paclitaxel to achieve an excellent result.Target volume of external beam radiation therapy and its coverage have been in debate for years among radiation oncologists.Pre-operative and postoperative target volumes are designed to optimize for disease control.Esophageal brachytherapy is effective in the palliation of dysphagia,but should not be given concomitantly with chemotherapy or external beam RT.The role of brachytherapy in multimodality management requires further investigation.On-going studies of multidisciplinary treatment in locally advanced cancer include:ZTOG1201 trial(a phaseⅡtrial of neoadjuvant and adjuvant CRT)and QUINTETT(a phaseⅢtrial of neoadjuvant vs adjuvant therapy with quality of life analysis).These trials hopefully will shed more light on the future management of esophageal cancer.

T cells in pancreatic cancer stroma:Tryptophan metabolism plays an important role in immunoregulation

Several studies have shown that the immune system is highly regulated by tryptophan metabolism,which serves as an immunomodulatory factor.The indoleamine 2,3-dioxygenase 1(IDO1),as an intracellular enzyme that participates in metabolism of the essential amino acid tryptophan in the kynurenine pathway,is an independent prognostic marker for pancreatic cancer(PC).First,overexpression of IDO1 inhibits the maturation of dendritic cells and T-cell proliferation in the liver and spleen.Second,the high expression of kynurenine induces and activates the aryl hydrocarbon receptor,resulting in upregulated programmed cell death protein 1 expression.Third,the induction of IDO1 can lead to loss of the T helper 17 cell/regulatory T cell balance,mediated by the proximal tryptophan catabolite from IDO metabolism.In our study,we found that overexpression of IDO1 upregulated CD8+T cells and reduced natural killer T cells in pancreatic carcinoma in mice.Hence,it may be essential to pay more attention to tryptophan metabolism in patients,especially those who are tolerant to immunotherapy for PC.

Robotic approach with neoadjuvant chemotherapy in adult Wilms’ tumor: A feasibility study report and a systematic review of the literature

Objective:The incidence of Wilms’tumor(WT)among adult individuals accounts for less than 1%of kidney cancer cases,with a prognosis usually less favorable when compared to younger individuals and an overall survival rate of 70%for the adult patients versus 90%for the pediatric cases.The diagnosis and treatment of WT are complex in the preoperative setting;neoadjuvant chemotherapy(NAC)or robotic surgery has rarely been described.This study aimed to review the literature of robotic surgery in WT and report the first adult WT management using both NAC and robotic strategy.Methods:We reported a case of WT managed in a multidisciplinary setting.Furthermore,according to Preferred Reporting Items for Systematic reviews and Meta-Analyses recommendations,a systematic review of the literature until August 2020 of WT treated with a robotic approach was carried out.Results:A 33-year-old female had a diagnosis of WT.She was scheduled to NAC,and according to the clinical and radiological response to a robotic radical nephrectomy with aortic lymph nodes dissection,she was managed with no intraoperative rupture,a favorable surgical outcome,and a follow-up of 25 months,which did not show any recurrence.The systematic review identified a total number of 230 cases of minimally invasive surgery reported in the literature for WT.Of these,approximately 15 patients were carried out using robotic surgery in adolescents while none in adults.Moreover,NAC has not been administered before minimally invasive surgery in adults up until now.Conclusion:WT is a rare condition in adults with only a few cases treated with either NAC or minimally invasive approach so far.The advantage of NAC followed by the robotic approach could lead to favorable outcomes in this complex scenario.Notwithstanding,additional cases of adult WT need to be identified and investigated to improve the oncological outcome.

Three-dimensional automatic artificial intelligence driven augmented-reality selective biopsy during nerve-sparing robot-assisted radical prostatectomy:A feasibility and accuracy study

Objective:To evaluate the accuracy of our new three-dimensional(3D)automatic augmented reality(AAR)system guided by artificial intelligence in the identification of tumour’s location at the level of the preserved neurovascular bundle(NVB)at the end of the extirpative phase of nerve-sparing robot-assisted radical prostatectomy.Methods:In this prospective study,we enrolled patients with prostate cancer(clinical stages cT1ce3,cN0,and cM0)with a positive index lesion at target biopsy,suspicious for capsular contact or extracapsular extension at preoperative multiparametric magnetic resonance imaging.Patients underwent robot-assisted radical prostatectomy at San Luigi Gonzaga Hospital(Orbassano,Turin,Italy),from December 2020 to December 2021.At the end of extirpative phase,thanks to our new AAR artificial intelligence driven system,the virtual prostate 3D model allowed to identify the tumour’s location at the level of the preserved NVB and to perform a selective excisional biopsy,sparing the remaining portion of the bundle.Perioperative and postoperative data were evaluated,especially focusing on the positive surgical margin(PSM)rates,potency,continence recovery,and biochemical recurrence.Results:Thirty-four patients were enrolled.In 15(44.1%)cases,the target lesion was in contact with the prostatic capsule at multiparametric magnetic resonance imaging(Wheeler grade L2)while in 19(55.9%)cases extracapsular extension was detected(Wheeler grade L3).3D AAR guided biopsies were negative in all pathological tumour stage 2(pT2)patients while they revealed the presence of cancer in 14 cases in the pT3 cohort(14/16;87.5%).PSM rates were 0%and 7.1%in the pathological stages pT2 and pT3(<3 mm,Gleason score 3),respectively.Conclusion:With the proposed 3D AAR system,it is possible to correctly identify the lesion’s location on the NVB in 87.5%of pT3 patients and perform a 3D-guided tailored nerve-sparing even in locally advanced diseases,without compromising the oncological safety in terms of PSM rates.

Modified albumin-bilirubin predicted survival of unresectable hepatocellular carcinoma patients treated with immunotherapy

BACKGROUND Modified albumin-bilirubin(mALBI)grade has been established as a survival determinant in hepatocellular carcinoma(HCC)patients who receive locoregional and targeted therapies.AIM To investigate whether mALBI could predict survival in unresectable HCC(uHCC)patients who were treated with atezolizumab plus bevacizumab(AB).METHODS A single-center,retrospective cohort study enrolled uHCC patients who received AB treatment between September 2020 and April 2023 and were followed up until June 2023.An association between mALBI and patient survival was determined using Cox proportional hazards analysis.RESULTS Of the 83 patients,67 patients(80.7%)were male with the mean age of 60.6 years.Among them,22 patients(26.5%)were classified as Barcelona Clinic Liver Cancer B,and 61 patients(73.5%)were classified as Barcelona Clinic Liver Cancer C.Cirrhosis was present in 76 patients(91.6%),with 58 patients classified as Child-Turcotte-Pugh(CTP)A and 18 as CTP B.The median overall survival(OS)and progression-free survival were 13.0 mo[95%confidence interval(CI):5.2-20.8]and 9.0 mo(95%CI:5.0-13.0),respectively.The patients were divided into two groups based on mALBI grades:42 patients(50.6%)in the mALBI 1+2a group;and 41 patients(49.4%)in the mALBI 2b+3 group.During the median follow-up period of 7.0 mo,the mALBI 1+2a group exhibited significantly better survival compared to the mALBI 2b+3 group,with a median OS that was not reached vs 3.0 mo(95%CI:0.1-6.0,P<0.001).In a subgroup of patients with CTP A,the mALBI 1+2a group also showed significantly longer survival compared to the mALBI 2b+3 group,with a median OS that was not reached vs 6.0 mo(95%CI:3.4-8.6,P<0.001).In the multivariate analysis,both CTP class and mALBI grade were independently associated with survival,with adjusted hazard ratios(95%CI)of 2.63(1.19-5.78,P=0.020)and 3.90(1.71-8.90,P=0.001),respectively.CONCLUSION mALBI grades can determine survival of uHCC patients receiving AB treatment,particularly those who have mildly impaired liver function.This highlights the importance of assessing mALBI before initiating AB treatment to optimize therapeutic efficacy in clinical practice.

Robot-assisted adrenalectomy:Step-by-step technique and surgical outcomes at a high-volume robotic center

Objective In the last years,robotic surgery was introduced in several different settings with good perioperative results.However,its role in the management of adrenal masses is still debated.In order to provide a contribution to this field,we described our step-by-step technique for robotic adrenalectomy(RA)and related modifications according to the type of adrenal mass treated.Methods We retrospectively analyzed 27 consecutive patients who underwent RA at Onze-Lieve-Vrouw hospital(Aalst,Belgium)between January 2009 and October 2022.Demographic,intra-and post-operative,and pathological data were retrieved from our prospectively maintained institutional database.Continuous variables are summarized as median and interquartile range(IQR).Categorical variables are reported as frequencies(percentages).Results Twenty-seven patients underwent RA were included in the study.Median age,body mass index,and Charlson's comorbidity index were 61(IQR:49-71)years,26(IQR:24-29)kg/m^(2),and 2(IQR:0-3),respectively,and 16(59.3%)patients were male.Median tumor size at computed tomography scan was 6.0(IQR:3.5-8.0)cm.Median operative time and blood loss were 105(IQR:82-120)min and 175(IQR:94-250)mL,respectively.No intraoperative complications were recorded.Overall postoperative complications rate was 11.1%,with a postoperative transfusion rate of 3.7%.A total of 10(37.0%)patients harbored malignant adrenal masses.Among them,3(11.1%)had adrenocortical carcinoma,6(22.2%)secondary metastasis,and 1(3.7%)malignant pheochromocytoma on final pathological exam.Only 1(10.0%)patient had positive surgical margins.Conclusion We described our step-by-step technique for RA,which can be safely performed even in case of high challenging settings as malignant tumors,pheochromocytoma,and large masses.The standardization of perioperative protocol should be encouraged to maximize the outcomes of this complex surgical procedure.

电离辐射诱导小鼠小肠隐窝和绒毛的基因表达分析

目的通过基因表达的芯片分析方法,观察电离辐射引起的小鼠小肠上皮隐窝和绒毛基因表达的改变,探讨隐窝细胞的DNA损伤和修复、细胞周期调控的特点。方法 20只5周龄C57/BL6小鼠雄性20～22 g,随机分组,对照组不经电离辐照,处理组经12 Gy电离辐射全身照射后,于4、8、24 h分离小肠隐窝和绒毛上皮细胞,用cDNA表达谱芯片分别检测隐窝和绒毛基因表达的动态变化,对上调或下调的基因进行聚类分析,并重点对DNA损伤修复相关和细胞周期相关基因进行分析。结果与对照组相比上调或下调2倍以上的基因(P<0.01)经聚类分析被归属为各细胞信号通路,其中主要涉及p53通路、MAPK通路、凋亡、细胞周期以及免疫反应(P<0.05),将P值排序发现p53通路、MAPK通路对隐窝的调控更为明显。各DNA修复途径代表基因在隐窝和绒毛中均有不同程度的上调表达,且与细胞周期的变化相一致。基因表达特点提示隐窝细胞以准确性高的方式(核苷酸外切修复、同源重组)进行DNA损伤修复,而绒毛细胞则以快速但易发生错误修复的方式(错配修复)恢复基因的完整性。结论 电离辐射诱导的DNA损伤反应与细胞分化程度相关,隐窝细胞对损伤更敏感。

Clinical significance of lymph node metastasis in gastric cancer

Gastric cancer,one of the most common malignancies in the world,frequently reveals lymph node,peritoneum,and liver metastases.Most of gastric cancer patients present with lymph node metastasis when they were initially diagnosed or underwent surgical resection,which results in poor prognosis.Both the depth of tumor invasion and lymph node involvement are considered as the most important prognostic predictors of gastric cancer.Although extended lymphadenectomy was not considered a survival benefit procedure and was reported to be associated with high mortality and morbidity in two randomized controlled European trials,it showed significant superiority in terms of lower locoregional recurrence and disease related deaths compared to limited lymphadenectomy in a 15-year followup study.Almost all clinical investigators have reached a consensus that the predictive efficiency of the number of metastatic lymph nodes is far better than the extent of lymph node metastasis for the prognosis of gastric cancer worldwide,but other nodal metastatic classifications of gastric cancer have been proposed as alternatives to the number of metastatic lymph nodes for improving the predictive efficiency for patient prognosis.It is still controversial over whether the ratio between metastatic and examined lymph nodes is superior to the number of metastatic lymph nodes in prognostic evaluation of gastric cancer.Besides,the negative lymph node count has been increasingly recognized to be an important factor significantly associated with prognosis of gastric cancer.

Primary gastric lymphoma

AIM: The purpose of this review is to describe the variousaspects of primary gastric lymphoma and the treatmentoptions currently available. METHODS: After a systematic search of Pubmed, Medscape and MDconsult, we reviewed and retrieved literature regarding gastric lymphoma. RESULTS: Primary gastric lymphoma is rare however, the incidence of this malignancy is increasing. Chronic gastritis secondary to Helicobacterpylori(H pylon) infection has been considered a major predisposing factor for MALT lymphoma.Immune histochemical marker studies and molecular biology utilizing polymerase chain reaction have facilitated appropriate diagnosis and abolished the need for diagnostic surgical resection. Advances in imaging techniques including Magnetic Resonance Imaging (MRI) and Endoscopic UItrasonography (EUS) have helped evaluation of tumor extension and invasion.The clinical course and prognosis of this disease is dependent on histopathological sub-type and stage at the time of diagnosis. Controversy remains regarding the best treatment for early stages of this disease. Chemotherapy, surgery and combination have been studied and shared almost comparable results with survival rate of 70-90%. However, chemotherapy possesses the advantage of preserving gastric anatomy.Radiotherapy alone has been tried and showed good results.Stage ⅢE, IVE disease treatment is solely by chemotherapy and surgical resection has been a remote consideration. CONCLUSION: We conclude that methods of diagnosis and staging of the primary gastric lymphoma have dramatically improved. The modalities of treatment are many and probably chemotherapy is superior because of high success rate,preservation of stomach and tolerable complications.

Role of cyclooxygenase-2 in the carcinogenesis of gastrointestinal tract cancers: A review and report of personal experience

选择 cyclooxygenase (艇长)-2 禁止者(coxibs ) 作为反煽动性的药之一被开发避免 non-steroidal 的各种各样的副作用反煽动性的药(NSAID ) 。然而， coxibs 也有一个能力禁止各种各样的类型的肿瘤开发 NSAID 的一样的方法。用细胞线和动物模型的许多试验性的研究表明了一个能力阻止 COX-2 禁止者的肿瘤增长。在为息肉 chemoprevention 执行使随机化的研究以后，与家庭腺瘤息肉病( FAP )在病人学习，它证明有 celecoxib 的治疗， coxibs 之一，显著地减少了颜色的数字在 2000 的表面的息肉，美国食物药品管理局(食物及药品管理局)立即为 FAP 病人同意了临床的使用 celecoxib 。然而，某 coxibs 最近被报导包括心脏病和击增加严肃的心血管的事件的风险。在这篇文章，我们在胃肠道的致癌作用考察 COX-2 的一个角色，例如食管，胃和 colorectum，并且也为胃肠道肿瘤的 chemoprevention 分析 coxibs 的前景。

Locally advanced nasopharyngeal carcinoma:Current and emerging treatment strategies

Although nasopharyngeal carcinoma(NPC)is a widespread malignant tumor,it is particularly frequent in Southeast Asia.Although T1 tumors can be effectively controlled with exclusive radiotherapy,this treatment modality is insufficient for most NPC patients,who present with locally advanced disease at diagnosis.In fact,for stages ranging from T2b N0 to T4 N3,definitive scientific evidence supports the use of concurrent platinum-based chemotherapy with standard external beam radiotherapy.This treatment approach has shown a statistically significant advantage in terms of overall survival,with respect to radiotherapy alone.Several trials have also investigated the use of neoadjuvant and adjuvant chemotherapy in combination with radiotherapy or chemo-radiotherapy.Platinum compounds,anthracyclines and taxanes are among the chemotherapy agents employed.This review focuses on the clinical results obtained in the field of adjuvant/concurrent/neoadjuvant chemotherapy for locally advanced NPC,for which exclusive concurrent chemo-radiotherapy currently represents the standard treatment approach.

STAT-3 correlates with lymph node metastasis and cell survival in gastric cancer

AIM:To investigate the correlation between gastric cancer growth and signal transducer and activator of transcription-3(STAT3) expression.METHODS:We assessed the expressions of STAT3,phosphor-STAT3(pSTAT3),suppressor of cytokine signaling-1(SOCS-1),survivin and Bcl-2 in gastric cancer patients after gastrectomy by immunohistochemical method.In addition,in situ hybridization was used to further demonstrate the mRNA expression of STAT3 in gastric cancer.RESULTS:With the univariate analysis,expressions of STAT3,pSTAT3,SOCS-1,survivin and Bcl-2,the size of primary tumor and the lymph node metastasis were found to be associated with the overall survival(OS) of gastric cancer patients.However,only pSTAT3 expression and the lymph node metastasis were identified as the independent factors of OS of gastric cancer with multivariate analysis.STAT3 expression was correlated with the lymph node metastasis.There were positive correlations between expressions of STAT3,survivin,Bcl-2 and pSTAT3 in gastric cancer,whereas there was negative correlation between STAT3 expression and SOCS-1 expression in gastric cancer.CONCLUSION:STAT3 can transform into pSTAT3 to promote the survival and inhibit the apoptosis of gastric cancer cells.SOCS-1 might be the valid molecular antagonist to inhibit the STAT3 expression in gastric cancer.

Granular cell tumor of stomach: A case report and review of literature

小粒的房间肿瘤(GCT ) 被 Abrikosoff 在 1926 第一次描述。是一个相对稀罕的瘤可以在皮或软纸巾通常发生在许多地点，而是大多数。在胃肠道的 GCT 的出现是稀罕的，财务近似为 8% 所有肿瘤，最普通的地点在之中是食管，而胃的本地化是很稀罕的。胃的 GCT 能是独居的或，更经常，与另外的胃肠的本地化联系了。尽管 GCT 通常是临床上并且组织学地良性的，一些恶意的案例被报导了。组织学地，这些肿瘤由在紧缩的“巢”和为 S-100 蛋白质的组织化学的染色支持的免疫里处理的多角形、纺锤形的房间组成从 Schwann 房间的建议推导。这个肿瘤的正确外科手术前的诊断能仅仅在 50% 所有病人被做，它总是基于内视镜的活体检视。Laparoscopic 或常规楔切除术代表选择的治疗。在这研究，作者与渗透性的模式与胃的一个独居的小粒的房间肿瘤报导了一个 49 岁的女人的一个案例，成功地与外科的切除术对待。文学的评论也有关恶意的形式在诊断标准上与强调被介绍。

Adjuvant chemotherapy for gastric cancer:Current evidence and future challenges

Gastric cancer still represents one of the major causes of cancer mortality worldwide.Patients survival is mainly related to stage,with a high proportion of patients with metastatic disease at presentation.Thus,the cure rate largely depend upon surgical resection.Despite the additional,albeit small,benefit of adjuvant chemotherapy has been clearly demonstrated,no general consensus has been reached on the best treatment option.Moreover,the narrow therapeutic index of adjuvant chemotherapy(i.e.,limited survival benefit with considerable toxicity)requires a careful assessment of expected risks and benefits for individual patients.Treatment choices vary widely based on the different geographic areas,with chemotherapy alone more often preferred in Europe or Asia and chemoradiotherapy in the United States.In the present review we discuss the current evidence and future challenges regarding adjuvant chemotherapy in curatively resected gastric cancer with particular emphasis on the recently completed landmark studies and meta-analyses.The most recent patient-level meta-analysis demonstrated the benefit of adjuvant chemotherapy over curative surgery;the same Authors also showed that disease free survival may be used as a surrogate end-point for overall survival.We finally discuss future research issues such as the need of economic evaluations,development of prognostic or predictive biomarkers,and the unmet clinical need of trials comparing perioperative chemotherapy with adjuvant treatment.

The endless tale of non-homologous end-joining

脱氧核糖核酸双海滨裂缝(DSB ) 被离子辐射和反应的氧种类在房间介绍。另外，他们通常在 V (D) J 再结合期间被产生，发展中的免疫系统的一个必要方面。有效地修理这些 DSB 的失败能在更高的脊椎动物的免疫系统导致染色体破裂，房间死亡，癌症的发作，和缺点。幸好，所有哺乳动物的房间拥有调停的二条酶的小径 DSB 的修理：相应再结合并且非相应加入结束(NHEJ ) 。NHEJ 过程利用捕获破脱氧核糖核酸分子的两结束，在 synaptic DNA 蛋白质建筑群一起带他们，并且最后修理脱氧核糖核酸裂缝的酶。在这评论，在 NHEJ 过程起一个作用的所有已知的酶被讨论，为这些酶的合作的一个工作模型在 DSB 修理期间被介绍。

Efficacy of rituximab in gastric diffuse large B cell lymphoma patients

AIM:To evaluate retrospectively the efficacy of rituximab plus chemotherapy in gastric diffuse large B cell lymphoma(DLBCL).METHODS:Sixty patients(median age:58 years)with histologically confirmed gastric DLBCL treated at four Italian institutions between 2000 and 2007,were included in this analysis.Patients were selected by stage (Ⅰ-Ⅳ,Lugano staging system),European Cooperative Oncology Group performance status(0-2)and treatment strategies.Treatment strategies were chemotherapy alone(group A,n=30)[scheduled as cyclophosphamide,doxorubicin,vincristine and prednisone (CHOP)and CHOP-like],and chemotherapy combined with rituximab(group B,n=30).The primary end point of the study was complete response(CR)rate;the secondary end points were disease-free survival (DFS)at 5 years and overall survival(OS).RESULTS:Median follow-up was 62 mo(range:31102 mo).We observed a significant difference between the two groups(A vs B)in terms of CR[76.6%(23/30) vs 100%,P=0.04)and DFS at 5 years[73.3%(22/30) vs 100%,P=0.03).To date,19 group A(63.3%) patients are alive and 11 have died,while all group B patients are alive.No significant differences in toxicity were observed between the two groups.CONCLUSION:Rituximab in combination with chemotherapy improves CR rate,DFS and OS.Further prospective trials are needed to confirm our results.

Is endoscopic ultrasound examination necessary in the management of esophageal cancer?

Despite substantial efforts at early diagnosis, accurate staging and advanced treatments, esophageal cancer(EC) continues to be an ominous disease worldwide. Risk factors for esophageal carcinomas include obesity, gastroesophageal reflux disease, hard-alcohol use and tobacco smoking. Five-year survival rates have improved from 5% to 20% since the 1970 s, the result of advances in diagnostic staging and treatment. As the most sensitive test for locoregional staging of EC, endoscopic ultrasound(EUS) influences the development of an optimal oncologic treatment plan for a significant minority of patients with early cancers, which appropriately balances the risks and benefits of surgery, chemotherapy and radiation. EUS is costly, and may not be available at all centers. Thus, the yield of EUS needs to be thoughtfully considered for each patient. Localized intramucosal cancers occasionally require endoscopic resection(ER) for histologic staging or treatment; EUS evaluation may detect suspicious lymph nodes prior to exposing the patient to the risks of ER. Although positron emission tomography(PET) has been increasingly utilized in staging EC, it may be unnecessary for clinical staging of early, localized EC and carries the risk of false-positive metastasis(over staging). In EC patients with evidence of advanced disease, EUS or PET may be used to define the radiotherapy field. Multimodality staging with EUS, crosssectional imaging and histopathologic analysis of ER, remains the standard-of-care in the evaluation of early esophageal cancers. Herein, published data regarding use of EUS for intramucosal, local, regional and metastatic esophageal cancers are reviewed. An algorithm to illustrate the current use of EUS at The University of Texas MD Anderson Cancer Center is presented.