Early adenocarcinoma mixed with a neuroendocrine carcinoma component arising in the gastroesophageal junction: A case report

BACKGROUND Early adenocarcinoma mixed with a neuroendocrine carcinoma(NEC)component arising in the gastroesophageal junctional(GEJ)region is rare and even rarer in young patients.Here,we report such a case in a 29-year-old Chinese man.CASE SUMMARY This patient presented to our hospital with a 3-mo history of dysphagia and regurgitation.Upper endoscopy revealed an elevated nodule in the distal esophagus 1.6 cm above the GEJ line,without Barrett’s esophagus or involvement of the gastric cardia.The nodule was completely resected by endoscopic submu-cosal dissection(ESD).Pathological examination confirmed diagnosis of intra-mucosal adenocarcinoma mixed with an NEC component,measuring 1.5 cm.Immunohistochemically,both adenocarcinoma and NEC components were positive for P53 with a Ki67 index of 90%;NEC was positive for synaptophysin and chromogranin.Next-generation sequencing of 196 genes demonstrated a novel germline mutation of the ERCC3 gene in the DNA repair pathway and a germline mutation of the RNF43 gene,a common gastric cancer driver gene,in addition to pathogenic somatic mutations in P53 and CHEK2 genes.The patient was alive without evidence of the disease 36 mo after ESD.CONCLUSION Early adenocarcinoma with an NEC component arising in the distal esophageal side of the GEJ region showed evidence of gastric origin.

Expression of gap junction genes connexin 32,connexin 43 and their proteins in hepatocellular carcinoma and normal liver tissues

AIM To investigate the significance andmechanism of cx32 mRNA,cx43 mRNA and theirproteins in hepatocarcinogenesis.METHODS Sixty-one cases of HCC and 14cases of normal liver tissues were detected byimmunohistochemical and in situ hybridization(ISH)methods.RESULTS In HCC grades Ⅰ,Ⅱ,Ⅲ and normalliver tissues,the positive rates of Cx32 proteinwere 55.6%,42.1%,18.2% and 92.9%,respectively.The detection rates of Cx43 proteinwere 44.4%,26.3%,12.1% and 78.6%,respectively.There was significant difference inCx32 and Cx43 protein between HCC and normalliver tissues(P【0.01).ISH the positive rates ofcx32 mRNA shown by ISH in HCC grades Ⅰ,Ⅱ,Ⅲ and normal liver tissues were 88.9%,84.2%,87.9% and 92.9%,respectively.Those of cx43mRNA were 77.8%,78.6%,78.8% and 85.7%,respectively.There was no statistical differencein the positive rates of cx32 mRNA and cx43mRNA between HCC and normal liver tissue(P】0.05).CONCLUSION The aberrant location of Cx32and Cx43 proteins could be responsible forprogression of hepatocarcinogenesis,and thedefect of cx genes in post-translationalprocessing might be the possible mechanism.

Autoantibodies: Potential clinical applications in early detection of esophageal squamous cell carcinoma and esophagogastric junction adenocarcinoma

Esophageal squamous cell carcinoma(ESCC)and esophagogastric junction adenocarcinoma(EGJA)are the two main types of gastrointestinal cancers that pose a huge threat to human health.ESCC remains one of the most common malignant diseases around the world.In contrast to the decreasing prevalence of ESCC,the incidence of EGJA is rising rapidly.Early detection represents one of the most promising ways to improve the prognosis and reduce the mortality of these cancers.Current approaches for early diagnosis mainly depend on invasive and costly endoscopy.Non-invasive biomarkers are in great need to facilitate earlier detection for better clinical management of patients.Tumor-associated autoantibodies can be detected at an early stage before manifestations of clinical signs of tumorigenesis,making them promising biomarkers for early detection and monitoring of ESCC and EGJA.In this review,we summarize recent insights into the iden-tification and validation of tumor-associated autoantibodies for the early detection of ESCC and EGJA and discuss the challenges remaining for clinical validation.

Primary advanced esophago-gastric melanoma:A rare case

Primary esophageal or gastric melanoma is a very rare disease with early metastasis. Due to its atypical symptom and less efficiency of chemotherapy and radiotherapy, the prognosis of esophageal or gastric melanoma is still very poor. Surgical resection remains the preferential treatment for esophageal or gastric melanoma. Here we present an extremely rare case of primary advanced esophago-gastric melanoma. Debulking surgery was performed without chemotherapy or radiotherapy. However, abdominal recurrence and hepatic metastases were found within one month by a postoperative follow-up computed tomography. Three and a half months after surgical resection, the patient died of extensive abdominal metastasis.

Application of computed tomography-based radiomics in differential diagnosis of adenocarcinoma and squamous cell carcinoma at the esophagogastric junction

BACKGROUND The biological behavior of carcinoma of the esophagogastric junction(CEGJ)is different from that of gastric or esophageal cancer.Differentiating squamous cell carcinoma of the esophagogastric junction(SCCEG)from adenocarcinoma of the esophagogastric junction(AEG)can indicate Siewert stage and whether the surgical route for patients with CEGJ is transthoracic or transabdominal,as well as aid in determining the extent of lymph node dissection.With the development of neoadjuvant therapy,preoperative determination of pathological type can help in the selection of neoadjuvant radiotherapy and chemotherapy regimens.AIM To establish and evaluate computed tomography(CT)-based multiscale and multiphase radiomics models to distinguish SCCEG and AEG preoperatively.METHODS We retrospectively analyzed the preoperative contrasted-enhanced CT imaging data of single-center patients with pathologically confirmed SCCEG(n=130)and AEG(n=130).The data were divided into either a training(n=182)or a test group(n=78)at a ratio of 7:3.A total of 1409 radiomics features were separately extracted from two dimensional(2D)or three dimensional(3D)regions of interest in arterial and venous phases.Intra-/inter-observer consistency analysis,correlation analysis,univariate analysis,least absolute shrinkage and selection operator regression,and backward stepwise logical regression were applied for feature selection.Totally,six logistic regression models were established based on 2D and 3D multi-phase features.The receiver operating characteristic curve analysis,the continuous net reclassification improvement(NRI),and the integrated discrimination improvement(IDI)were used for assessing model discrimination performance.Calibration and decision curves were used to assess the calibration and clinical usefulness of the model,respectively.RESULTS The 2D-venous model(5 features,AUC:0.849)performed better than 2D-arterial(5 features,AUC:0.808).The 2D-arterial-venous combined model could further enhance the performance(AUC:0.869).The 3D-venous model(7 features,AUC:0.877)performed better than 3D-arterial(10 features,AUC:0.876).And the 3D-arterial-venous combined model(AUC:0.904)outperformed other single-phase-based models.The venous model showed a positive improvement compared with the arterial model(NRI>0,IDI>0),and the 3D-venous and combined models showed a significant positive improvement compared with the 2D-venous and combined models(P<0.05).Decision curve analysis showed that combined 3D-arterial-venous model and 3D-venous model had a higher net clinical benefit within the same threshold probability range in the test group.CONCLUSION The combined arterial-venous CT radiomics model based on 3D segmentation can improve the performance in differentiating EGJ squamous cell carcinoma from adenocarcinoma.

Do the expressions of gap junction gene connexin messenger RNA in noncancerous liver remnants of patients with hepatocellular carcinoma correlate with postoperative recurrences?

AIM: To investigate whether the changes of gap junction gene connexin messenger RNA in the noncancerous liver tissue of patients with hepatocellular carcinoma (HCC) could play a significant role in its postresection recurrence.METHODS: Seventy-nine consecutive patients having undergone curative resection for HCC entered this study.Using a reverse-transcription polymerase chain reaction (RT-PCR)-based assay, connexin (Cx) 26, connexin (Cx)32 and connexin (Cx) 43 mRNAs were determined prospectively in noncancerous liver tissues from these 79 patients and in the liver tissues from 15 controls. The correlations between connexin mRNA expression and the clinicopathological variables and outcomes (tumor recurrence and recurrence related mortality) were studied.RESULTS: Compared with liver tissues of control patients,the expression of Cx 32 mRNA in noncancerous liver tissues was significantly lower (mean: 0.715 vscontrol 1.225,P＜0.01), whereas the decreased Cx 26 mRNA (mean:0.700 vs of control 1.205,P＞0.05) and increased Cx 43 mRNA (mean: 0.241 vscontrol 0.100, P＞0.05) had no statistical significance. We defined the value of Cx 32 mRNA or Cx 26mRNA below 0.800 as a lower value. By multivariate analysis for noncancerous livers, a lower value of Cx 32 mRNA correlated significantly with a risk of HCC recurrence and recurrence-related mortality. The lower value of Cx 26 mRNA did not correlate with recurrence and mortality. The increased value of Cx43 mRNA also did not correlate with postoperative recurrence and recurrence-related mortality. By multivariate analysis, other significant predictors of HCC recurrence included vascular permeation, cellular dedifferentiation, and less encaps-ulation. The other significant parameter of recurrence related mortality was vascular permeation.CONCLUSION: The decreased expression of Cx 32 mRNA in noncancerous liver tissues plays a significant role in the prediction of postoperative recurrence of HCC.

Up-Regulation of the Gap Junction Intercellular Communication by Tea Polyphenol in the Human Metastatie Lung Carcinoma Cell Line

Our previous study has proven that tea polyphenol has a role in lung neoplasms. The present communication was to investage the anti-proliferation effect of tea polyphenol on the PG cells, which was a high metastatic human lung carcinoma cell line, by 3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-diphenytetrazoliumromide (MTT) cell viability assay, and to study the change of intracellular calcium concentration, connexin43 (Cx43) expression, gap junctional intercellular communication (GJIC) and cell cycle distribution after the tea polyphenol treatment by laser scanning confocal microscopy and flow cytometry. The results showed that 1) tea polyphenol could kill the PG cells in a dose-depent manner via inhibiting the PG cell proliferation and blocking the PG cell cycle progression staying in G0/G1 phase and not transfering in S and G2/M phases to reduce the PG cell proliferation index;2) the increases of intracellular calcium concentration, GJIC and Cx43 expression were related with the tea polyphenol doses. The data suggested that tea polyphenol could inhibit the growth of PG cells, which mechanism was associated with the up-regulation of GJIC.

Tuberous sclerosis patient with neuroendocrine carcinoma of the esophagogastric junction:A case report

BACKGROUND Tuberous sclerosis complex(TSC)is a rare inherited disease with non-cancerous tumor growths in the skin,brain,kidneys,heart,and lungs.The co-occurrence of neuroendocrine neoplasm(NEN)with TSC is even rarer.There have been few reports on the relationship between TSC and neuroendocrine tumors(NETs),and fewer on the relationship between TSC and neuroendocrine carcinoma(NEC),a subtype of NEN.This is the first reported case of NEC occurring at the esophagogastric junction in a patient with TSC.CASE SUMMARY A 46-year-old woman visiting our hospital for the treatment of TSC was admitted to the emergency department with tarry stools and dizziness.Computed tomography scans revealed thickness of the gastric cardia,multiple metastatic lesions of the liver,and enlarged lymph nodes near the lesser curvature of the stomach.Esophagogastroduodenoscopy revealed a type 3 tumor located from the esophagogastric junction to the fundus,and the pathological diagnosis by biopsy was NEC.The patient was treated with seven courses of cisplatin+irinotecan,followed by eight courses of ramucirumab+nab-paclitaxel,one course of nivolumab,and two courses of S-1+oxaliplatin.Twenty-three months after the first treatment,the patient died because of disease progression and deterioration of the general condition.CONCLUSION This case of NEC occurring in a patient with TSC indicates a difference in the occurrence of NETs and NECs.

The extent and value of lymphadenectomy in the surgical treatment of gastroesophageal junction carcinoma

Objective： We studied the extent and value of the lymphadenectomy in surgical treatment of carcinoma of gastroesophageal junction （GEJ）. Methods： 217 patients with GEJ who underwent surgical resection were retrospectively analyzed. The extent of lymphadenectomy was divided into 5 types （DO to D4） and the curability of operation was graded as A, B and C. Results： The patients had been treated as follows： 186 with proximal gastrectomy, 31 with total gastrectomy, 97 with a combined-visceral resection. The patients who underwent D1, D2 and D3 lymphadenectomy were respectively 158, 58 and 1. The patients who were performed with resection of grade A, B and C were 53, 107 and 57 respectively. All patients were performed with a lymphadenectomy and well registered. The lymph node metastasis occurred in 157 cases （72.4%）. The lymph node metastasis rate in the group 1, 2, 3, 4, 7, 9, 12 and 110 as well as in the pulmonary ligament group were higher than other groups. 2868 lymph nodes were removed, in which 655 （22.8%） demonstrated the existence of metastasis. The total lymph node metastatic degree in these groups was higher compared to the other groups. Conclusion： The survival rate in the D1 lymphadenectomy and D2 is similar for all patients, and there may be some differences in the 2nd and 3rd years for the DI lymphadenectomy and D2 in the stage-Ⅲb patients. The survival rate of D2 lymphadenectomy in stage Ⅲb is better than D1 and that of D2 lymphadenectomy is superior to D1 in stage-Ⅳ patients. The survival rate of grade A and B operation is much better than grade C, and the survival rate of grade A is also higher than B.

Role of stenting in the palliation of gastroesophageal junction cancer: A brief review

Gastroesophageal junction cancer has an increasing in-cidence in western countries. It is inoperable when firstmanifested in more than 50% of cases. So, palliationis the only therapeutic option for the advanced diseaseto relieve dysphagia and its consequences in weakenedpatients with an estimated mean survival under 6 mo.This article has tried to identify trends focusing on cur-rent information about the best palliative treatment,with an emphasis on the role of stenting. Self-expand-ing stent placement, either metal or plastic, is the mainmanagement option. However, this anatomical loca-tion creates some particular problems for stent safetyand effectiveness which may be overcome by properlydesigned novel stents. The stents ensure a good qual-ity of life and must be preferred over other alterna-tive methods of loco-regional modalities, i.e., externalradiation, laser thermal or photodynamic therapy. Al-though stent placement is generally a simple, safe andeffective method, there are sometimes complications,increasing the morbidity and mortality rate. Bypassoperative procedures have now been abandoned as afirst choice. The stomach instead of the colon must beused for a bypass operation when it is needed. Chemo-therapy, despite the toxicity, and intraluminal radiation(brachytherapy) have a well-defined role.

Sporadic ganglioneuromatosis of esophagogastric junction in a patient with gastro-esophageal reflux disorder and intestinal metaplasia

A 58-year-old female with a recurrent history of upper abdominal pain and intermittent dysphagia underwent endoscopic evaluation that demonstrated an irregular and nodular esophago-gastric （EG） junction and grade I erosive esophagitis. Biopsies showed prominent intestinal metaplasia of Barrett＇s type without dysplasia, chronic inflammation and multiple aggregates of large cells within the mucosal lamina propria, some with spindle shaped nuclei. Immunohistochemistry stains for keratins AE-1/ AE-3 were negative, while S-100 and NSE were positive. This, together with routine stains, was diagnostic for mucosal ganglioneuromatosis. The background of chronic inflammation with intestinal type metaplasia was consistent with long-term reflux esophagitis. No evidence of achalasia was seen. Biopsies of gastric antrum and fundus were unremarkable, without ganglioneural proliferation. Colonoscopy was unremarkable. No genetic syndromes were identified in the patient including familial adenomatous polyposis and multiple endocrine neoplasia type Ⅱ b （MEN Ⅱ b）. Iansoprazole （Prevacid） was started by oral administration each day with partial relief of symptoms. Subsequent esophagogastroscopy repeated at 4 mo showed normal appearing EG junction. Esophageal manometry revealed a mild nonspecific lower esophageal motility disorder. Mild motor dysfunction is seen with gastro-esophageal reflux disease （GERD） and we feel that the demonstration of localized ganglioneuromatosis was not likely related etiologically. In the absence of findings that might suggest neural hypertrophy, such as achalasia, the nodular mucosal irregularity seen with this instance of ganglioneuromatosis may, however, have exacerbated the patient＇s reflux.

Nimbolide inhibits tumor growth by restoring hepatic tight junction protein expression and reduced inflammation in an experimental hepatocarcinogenesis

BACKGROUND Altered tight junction(TJ)proteins are correlated with carcinogenesis and tumor development.Nimbolide is a tetranotriterpenoid that has been shown to have antioxidant and anti-proliferative properties;however,its anticancer effects and molecular mechanism in hepatocellular carcinoma(HCC)remains obscure.AIM To investigate the effect of nimbolide on TJ proteins,cell cycle progression,and hepatic inflammation in a mouse model of HCC.METHODS HCC was induced in male Swiss albino mice(CD-1 strain)by a single intraperitoneal injection of 100 mg/kg diethylnitrosamine(DEN)followed by 80 ppm N-nitrosomorpholine(NMOR)in drinking water for 28 wk.After 28 wk,nimbolide(6 mg/kg)was given orally for four consecutive weeks in DEN/NMOR induced HCC mice.At the end of the 32nd week,all the mice were sacrificed and blood and liver samples were collected for various analyses.Macroscopic examinations of hepatic nodules were assessed.Liver histology and HCC tumor markers such as alpha-fetoprotein(AFP)and glypican-3 were measured.Expression of TJ proteins,cell proliferation,and cell cycle markers,inflammatory markers,and oxidative stress markers were analyzed.In silico analysis was performed to confirm the binding and modulatory effect of nimbolide on zonula occludens 1(ZO-1),nuclear factor of kappa light polypeptide gene enhancer in B-cells(NF-κB),and tumor necrosis factor alpha(TNF-α).RESULTS We found nimbolide treatment at a concentration of 6 mg/kg to HCC mice reduced hepatic tumor size by 52.08%and tumor volume(P<0.01),and delayed tumor growth in HCC mice with a concomitant reduction in tumor markers such as AFP levels(P<0.01)and glypican-3 expression(P<0.05).Furthermore,nimbolide treatment increased tight junction proteins such as ZO-1 and occludin expression(P<0.05,respectively)and reduced ZO-1 associated nucleic acid binding protein expression(P<0.001)in HCC mice liver.Nimbolide treatment to HCC mice also inhibited cell proliferation and suppressed cell cycle progression by attenuating proliferating cell nuclear antigen(P<0.01),cyclin dependent kinase(P<0.05),and CyclinD1(P<0.05)expression.In addition,nimbolide treatment to HCC mice ameliorated hepatic inflammation by reducing NF-κB,interleukin 1 beta and TNF-αexpression(P<0.05,respectively)and abrogated oxidative stress by attenuating 4-hydroxynonenal expression(P<0.01).Molecular docking studies further confirmed that nimbolide interacts with ZO-1,NF-κB,and TNF-α.CONCLUSION Our current study showed for the first time that nimbolide exhibits anticancer effect by reducing tumor size,tumor burden and by suppressing cell cycle progression in HCC mice.Furthermore,nimbolide treatment to HCC mice ameliorated inflammation and oxidative stress,and improved TJ proteins expression.Consequently,nimbolide could be potentially used as a natural therapeutic agent for HCC treatment,however further human studies are warranted.

Basic Investigations EXPRESSION OF GAP JUNCTION PROTEIN Cx43 IN CULTURED HUMAN NORMAL AND MALIGNANT LUNG CELLS

Gap junctional intercellular communicationexchange of small molecules and ions between contiguous cells through membranous gap junctional channelsis essential for growth control and tissue homecotasis. This work concerns the functional expression of gap junction protein connexin 43 (Cx43) in normal human lung cells and the changes in lung carcinoma cells. By. using Northern blot hybridization analysis and Cx43 immunocytochemical methods, it was otherved that cultured normal human embryonic lung cells expressed a high level of Cx43 in both mRNA and protein levels.The Cx43 immunofluorescence was localized at cell membrane regions corresponding to the location of gap junctions. These normal lung cells were competent of intercellular communication function as detected by Lucifer yellow dye transfer. In contrast to normal celis, Cx43 mRNA and protein was not detectable in the carcinoma PG cell line. These tumor cells were defective of intercellular communication function. These results demonstrate that Cx43 is expressed in normal cultured human embryonic lung cells but not in lung tumor cells. The lack of intercellular communication in the lung tumor cell line correlates with dysfunctional intercellular communication. The suggestive role of Cx as a tumor suppersor gene is discussed.

Mixed epithelial and stromal tumour with extension to vesicoureteric junction

Mixed epithelial and stromal tumour(MEST)is an uncommon renal tumour with a tendency to protrude into the collecting system.We present a 50-year-old woman with a renal tumour extending up to the vesicoureteric junction(VUJ)who was suspected to have an upper tract transitional cell carcinoma for which a nephroureterectomy was performed.Histopathologic examination revealed a MEST arising from the kidney and extending up to the VUJ.To the best of our knowledge,this is the first report of a renal MEST with extension to the VUJ.

Junctional adhesion molecule-A(JAM-A)in gynecological cancers:Current state of knowledge

Junctional adhesion molecule-A(JAM-A),also known as the F11 receptor(F11R),is one of the tight junction components.JAM-A is a transmembrane glycoprotein that regulates many cellular processes,i.e.,angiogenesis,leukocyte transendothelial migration,intercellular permeability,epithelial-to-mesenchymal transition,and platelet activation.Of note,it is involved in the pathogenesis of various cancer types,including gynecological cancers.Only a few studies are available about this cancer type.Observed aberrant JAM-A expression in gynecological cancers correlates with poor patient prognosis.To the best of our knowledge,conflicting JAM-A roles in various cancer types suggest that its involvement is complex and tumor-type specific.The underlying molecular mechanisms and pathways responsible for JAM-A functions were not fully elucidated and need to be identified.Finding appropriate novel molecular cancer biomarkers may reduce observed very high mortality rates and could contribute to personalized treatment development.The main aim of the present viewpoint article is to report the current knowledge about JAM-A participation in gynecological malignancies.

完全腹腔镜近端胃癌切除术的临床疗效分析

目的 分析完全腹腔镜近端胃切除食管残胃吻合的临床疗效,为治疗早期近端胃癌提供新的手术方法。方法 回顾性分析2019年1月-2021年6月于解放军总医院第一医学中心普通外科医学部行近端胃切除术的80例早期胃癌患者的临床资料。根据手术方式不同分为完全腹腔镜近端胃癌切除术组(n=36)与腹腔镜辅助近端胃癌切除术组(n=44)。比较两组围手术期情况、远期并发症发生情况及生存状况。结果 完全腹腔镜近端胃癌切除术组腹部切口长度[(59.9±4.7) mm vs.(119.7±8.3) mm,P<0.001]、首次排气时间[(58.2±15.3) h vs.(66.8±16.4) h,P=0.019]及术后住院时间[(7.6±1.1) d vs.(9.2±1.3) d,P<0.001]均短于腹腔镜辅助近端胃癌切除术组,手术时间[(186.9±16.4) min vs.(154.0±17.2) min,P<0.001]长于腹腔镜辅助近端胃癌切除术组。两组术中出血量、淋巴结清扫数目和首次进流食时间差异无统计学意义(P>0.05),且均未发生需外科干预的早期并发症。随访期间两组无患者死亡,未出现复发或转移。完全腹腔镜近端胃癌切除术组反流性食管炎发生率低于腹腔镜辅助近端胃癌切除术组,差异有统计学意义[16.7%(6/36) vs.38.6%(17/44),P=0.031]。两组胃动力不足、残胃炎、吻合口狭窄、吻合口溃疡发生率差异无统计学意义(P>0.05)。结论 完全腹腔镜近端胃切除食管残胃吻合具有安全性好、术后恢复快、抗反流等特点,值得临床应用推广。

Holliday交叉识别蛋白是肾透明细胞癌的潜在预测和预后生物标记物

目的探讨Holliday交叉识别蛋白(HJURP)在肿瘤发生、进展及免疫治疗中的作用。方法采用TCGA、GTEx、SangerBox和TIMER 2.0数据库等生物信息学方法分析HJURP在各类癌症中的表达水平及其与预后、临床分期和免疫细胞浸润的关联。利用LinkedOmics数据库分析肾透明细胞癌(KIRC)中HJURP的相关基因及其潜在功能。通过免疫组织化学分析、Western blotting和qRT-PCR实验验证HJURP在KIRC中的表达,并设计靶向HJURP的小干扰RNA,评估其对KIRC细胞增殖、迁移能力的影响。结果HJURP在包含KIRC的26种肿瘤组织中表达升高(P<0.05),且与包括KIRC的5种肿瘤患者的预后呈负相关(P<0.05)。HJURP的表达水平与肿瘤的临床分期及免疫细胞浸润密切相关。在KIRC中,HJURP表达升高(P<0.0001),且与TNM分期(P<0.05)、Stage分期(P<0.01)及免疫细胞浸润呈正相关。基因本体论功能分析结果显示:HJURP在生物学过程中主要富集于生物调节和代谢过程等;在细胞组分方面主要富集于细胞膜与细胞核等;在分子功能方面主要富集于蛋白质结合和离子结合等。组织和细胞水平实验显示,HJURP在KIRC中高表达(P<0.001),且沉默HJURP抑制KIRC细胞的增殖与迁移(P<0.01)。结论HJURP可作为KIRC预后和免疫治疗的预测因子,并在KIRC细胞的恶性行为中发挥促进作用。

Effectiveness and tolerability of programmed cell death protein-1 inhibitor+chemotherapy compared to chemotherapy for upper gastrointestinal tract cancers

BACKGROUND The combination of programmed cell death protein-1(PD-1)inhibitor and che-motherapy is approved as a standard first-or second-line treatment in patients with advanced oesophageal or gastric cancer.However,it is unclear whether this combination is superior to chemotherapy alone.AIM To assess the comparative effectiveness and tolerability of combining PD-1 inhibitors with chemotherapy vs chemotherapy alone in patients with advanced gastric cancer,gastroesophageal junction(GEJ)cancer,or oesophageal carcinoma.METHODS We searched the PubMed and Embase databases for studies that compared the efficacy and tolerance of PD-1 inhibitors in combination with chemotherapy vs chemotherapy alone in patients with advanced oesophageal or gastric cancer.We employed either random or fixed models to analyze the outcomes of each clinical trial,en-compassing data on overall survival(OS),progression-free survival(PFS),objective response rate,and adverse events(AEs).RESULTS Nine phase 3 clinical trials(7016 advanced oesophageal and gastric cancer patients)met the inclusion criteria.Our meta-analysis demonstrated that the pooled PD-1 inhibitor+chemotherapy group had a significantly longer OS than the chemotherapy-alone group[hazard ratio(HR)=0.76,95%confidence interval(CI):0.71-0.81];the pooled PFS result was consistent with that of OS(HR=0.67,95%CI:0.61-0.74).The count of patients achieving an objective response in the PD-1 inhibitor+chemotherapy group surpassed that of the chemotherapy-alone group[odds ratio(OR)=1.86,95%CI:1.59-2.18].AE incidence was also higher in the combination-therapy group than in the chemotherapy-alone group,regardless of whether≥grade 3 only(OR=1.30,95%CI:1.07-1.57)or all AE grades(OR=1.88,95%CI:1.39-2.54)were examined.We performed a subgroup analysis based on the programmed death-ligand 1(PD-L1)combined positive score(CPS)and noted extended OS and PFS durations within the CPS≥1,CPS≥5,and CPS≥10 subgroups of the PD-1 inhibitor+chemotherapy group.CONCLUSION In contrast to chemotherapy alone,the combination of PD-1 inhibitor and chemotherapy appears to present a more favorable option for initial or subsequent treatment in patients with gastric cancer,GEJ tumor,or oesophageal cancer.This holds true particularly for individuals with PD-L1 CPS scores of≥5 and≥10.

胸段食管癌及食管胃交界部癌根治术后患者生存质量影响因素的研究

目的:对行食管及食管胃交界部癌根治术的372例生存患者进行随访,分析不同因素对生存质量的影响,以有利于采取相应的综合性干预措施。方法:通过一般情况问卷、欧洲癌症研究和治疗组织研制的生存质量核心问卷QLQ-C30、食管癌专用量表OES-18电话、信访患者。选取性别、年龄、户籍等11个变量,采用t检验或单因素方差分析比较各组患者在生存质量得分方面的差异;多元线性回归分析这些因素对生存质量的影响。结果:不同性别、年龄对患者生存质量的影响不同;非自费患者(包括医保、公费、合作医疗等)在社会功能方面的困扰大于自费患者;性格外向患者在躯体、情感、认知、社会、角色功能、总体健康状况方面均优于性格内向患者;患者在知情情况下,角色功能优于不知情的情况,呼吸功能受到困扰较小;精神良好患者在情感功能、呼吸功能、食欲方面较其它两组表现较好,精神较差患者在躯体功能、疼痛、睡眠、便秘方面表现较差;术后1～2年患者的认知功能较好,腹泻的困扰较其它两组明显,术后5年以上的患者角色功能、总体健康状况较好。结论:不同因素影响食管及食管胃交界部癌患者的不同领域,临床上应该采取综合性措施以改善患者的生存质量。

沙利度胺对前列腺癌PC-3细胞的增殖及细胞缝隙连接通讯的影响

目的:观察沙利度胺对前列腺癌PC-3细胞增殖和凋亡的作用及对PC-3细胞中Cx43表达水平的影响。方法:将处于对数生长期的前列腺癌PC-3细胞分别给予递增浓度的沙利度胺(0、12.5、25、50、100μg/mL)处理24 h和48 h。采用CCK-8法检测不同浓度沙利度胺对PC-3细胞的增殖抑制影响,Annexin V-FITC/PI双染色法检测细胞凋亡情况,RT-PCR法检测Cx43mRNA的表达及Westernblot检测Cx43蛋白的表达。结果:沙利度胺浓度在25～100μg/mL能明显抑制PC-3细胞体外增殖,随着时间、浓度增加,抑制率相应升高。不同浓度组沙利度胺处理PC-3细胞24～48 h后,Cx43 mRNA和蛋白有不同程度的升高(P<0.05)。结论:沙利度胺可通过抑制人前列腺癌PC-3细胞增殖、诱导其凋亡,产生抗肿瘤作用。沙利度胺可上调前列腺癌PC-3细胞Cx43mRNA及蛋白的表达水平,并可能促进前列腺癌PC-3细胞的细胞缝隙连接通讯功能的恢复,从而抑制肿瘤生长。