Value of c-Met for Predicting Progression of Precancerous Gastric Lesions in Rural Chinese Population

Objective： To investigate the value of c-Met in predicting progression of precancerous gastric lesions. Methods： A population-based study was conducted to detect the overexpression of c-Met by immunohisto- chemical analysis in 124 subjects with precancerous gastric lesions. Odds ratio （OR） and 95% confidence interval （95% CI） were calculated for the association of c-Met overexpression with the risk of advanced gastric lesions. Results： The positive rates of c-Met were 55.7% in intestinal metaplasia （IM） and 64.8% in dysplasia （DYS）, respectively. Stratified analysis indicated that the proportion of c-Met overexpression was 71.4% for IM progressive group, significantly higher than that for IM persistent group （40.0%, P〈O.05）. Compared to the IM persistent group, unconditional logistic regression showed that OR of c-Met overexpression for the IM progressive group was 7.426 （95% Cl： 2.084-26.398）. Conclusion： c-Met plays an important role in gastric carcinogenesis. Detection of c-Met is of value in predicting progression of precancerous gastric lesions from IM to DYS.

Significance of HER2 protein expression and HER2 gene amplification in colorectal adenocarcinomas

BACKGROUND Human epidermal growth factor receptor 2(HER2) is an oncogenic driver, and a well-established therapeutic target in breast and gastric cancers. While the role of HER2 as a prognostic biomarker in colorectal adenocarcinomas(CRCs) remains uncertain, its relevance as a therapeutic target has been established. We undertook the present study to evaluate the frequency of HER2 expression in CRC and to correlate it with various clinicopathological variables.AIM To correlate HER2 protein expression and HER2 gene amplification with clinicopathological features and survival in surgically resected CRC.METHODS About 1195 consecutive surgically resected CRCs were analyzed by immunohistochemical staining(IHC) to assess HER2 protein expression, and 141 selected tumors were further evaluated by fluorescence in situ hybridization(FISH) to assess HER2 gene amplification. Follow-up information was availablefor 1058 patients, and using this information we investigated the prevalence of HER2 protein overexpression and gene amplification in a large series of surgically resected CRCs, and evaluated the relationship between overexpression and clinicopathological parameters and prognosis.RESULTS HER2 IHC scores of 3+, 2+, 1+, and 0 were seen in 31(2.6%), 105(8.8%), 475(39.7%), and 584(48.9%) tumors, respectively. HER2 gene amplification was seen in 24/29 tumors with an IHC score of 3+(82.8%; unreadable in 2/31), 12/102 tumors with an IHC score of 2+(11.8%; unreadable in 2/104), and 0 tumors with IHC score of 1+(0/10). HER2 gene amplification was seen in 36/1191 tumors(3.0%; unreadable in 4/1195). Among the tumors with HER2 IHC scores of 3+and 2+, the mean percentage of tumor cells with positive IHC staining was 90%(median 100%, range 40%-100%) and 67%(median 75%, range 5%-95%),respectively(P < 0.05). Among tumors with IHC scores of 2+, those with HER2 gene amplification had a higher number of tumors cells with positive IHC staining(n = 12, mean 93%, median 95%, range 90%-95%) than those without(n =90, mean 70%, median 50%, range 5%-95%)(P < 0.05). HER2 gene status was significantly associated with distant tumor metastasis and stage(P = 0.028 and0.025). HER2 protein overexpression as measured by IHC or HER2 gene amplification as measured by FISH was not associated with overall survival(OS)or disease-specific survival for the overall group of 1058 patients. However,further stratification revealed that among patients with tubular adenocarcinomas who were 65 years old or younger(n = 601), those exhibiting HER2 gene amplification had a shorter OS than those without(mean: 47.9 mo vs 65.1 mo, P =0.04). Among those patients with moderately to poorly differentiated tubular adenocarcinomas, those with positive HER2 tumor IHC scores(2+, 3+) had a shorter mean OS than those with negative HER2 IHC scores(0, 1+)(47.2 mo vs64.8 mo, P = 0.033). Moreover, among patients with T2 to T4 stage tumors, those with positive HER2 IHC scores also had a shorter mean OS than those with negative HER2 IHC scores(47.1 mo vs 64.8 mo, P = 0.031).CONCLUSION HER2 protein levels are correlated with clinical outcomes, and positive HER2 expression as measured by IHC confers a worse prognosis in those patients 65 years old or younger with tubular adenocarcinomas.

Study on biological characters of SGC7901 gastric cancer cell-dendritic cell fusion vaccines

瞄准：检测 SGC7901 胃的癌症的生物人物房间树枝状的房间熔化疫苗。方法：推迟的生活 SGC7901 胃的癌症房间和树枝状的房间被导致是由聚乙二醇的 fusioned。纯熔化房间被选择文化与 HAT/HT 文化系统获得。熔化房间在文化的不同时间点被数，他们的生长曲线被拉反映他们的增生的活动。熔化房间在培养基也是有教养的调查他们是否能长成房间克隆。MTT 方法被用来在 T 淋巴细胞的增长上测试熔化房间的刺激能力。而且，熔化细胞被种进裸体老鼠观察他们是否能在这种免疫不全动物长成新种的肿瘤。结果：熔化房间比他们的父母房间有更弱的增生的活动和克隆能力。当他们是有教养的时，房间的计数没显著地增加，他们也不能在培养基长成房间克隆。在种了进裸体老鼠以后，熔化房间不能长成新种的肿瘤。T 淋巴细胞的增长上的熔化房间的刺激能力显著地比他们的父母树枝状的房间被增加。结论：SGC7901 胃的癌症房间树枝状的房间熔化疫苗比他们的父母房间有弱得多的增生的能力，但是他们使能力强壮激怒 T 淋巴细胞并且没有能力在免疫不全动物长成新种的肿瘤。这些是他们的反肿瘤简历治疗的生物基础。

Ovarian growing teratoma syndrome with multiple metastases in the abdominal cavity and liver:A case report

BACKGROUND Growing teratoma syndrome(GTS)is an unusual presentation of an amazing transformation of teratoma from malignant to benign on pathology during or after systemic or intraperitoneal chemotherapy.The definitive pathogenesis is still not fully understood due to the lack of large-sample studies.CASE SUMMARY A 53-year-old woman underwent radical surgery and postoperative intraperitoneal chemotherapy due to immature teratoma of the right ovary at the age of 28.She remained well during a 25-year follow-up period after surgery.Multiple asymptomatic solid masses were found in the liver on ultrasonography a month ago.Enhanced computed tomography(CT)of the abdomen revealed multiple masses in the abdominal cavity.The largest one was located in the posterior peritoneum next to the sixth segment of the right liver,about 7.9 cm×7.5 cm in size.Three masses were present inside the liver,and one mass was in the right pelvic floor.Multiple lumps in the abdominal cavity were completely removed by surgery.During the operation,multiple space-occupying lesions were seen,ranging in size from 0.5 to 3 cm,and grayish white in color and hard in texture.Ovarian GTS was finally diagnosed based on postoperative pathology.After surgery,she recovered uneventfully.During a 3-year follow-up,the patient remained free of the disease without any recurrence on CT scan.CONCLUSION GTS is a rare phenomenon characterized by conversion of immature teratoma to mature one during or after chemotherapy and presents as growing and metastasizing masses.The pathogenesis of GTS is unclear,and the prognosis is good after surgical resection.

Fabry Disease with Aseptic Meningitis:A Case Series and Literature Review of an Underestimated Clinical Presentation

Objective Fabry disease(FD)is an X-linked lysosomal storage disease caused by the mutation in theα-galactosidase A gene that leads to a consequently decreasedα-galactosidase A enzyme activity and a series of clinical presentations.However,FD accompanied with aseptic meningitis can be relatively scarce and rarely reported,which leads to significant clinical misdiagnosis of this disease.Methods Sixteen patients diagnosed with FD based on a decreased activity ofα-galactosidase A enzyme and/or genetic screening were identified through a 6-year retrospective chart review of a tertiary hospital.Clinical presentations,brain magnetic resonance imaging,cerebrospinal fluid analysis,treatment and outcome data were analyzed in cases of aseptic meningitis associated with FD.Results Three out of 16 cases exhibited aseptic meningitis associated with FD.There was one female and two male patients with a mean age of 33.3 years.A family history of renal failure or hypertrophic cardiomyopathy was found in 3 cases.All cases presented with a persistent or intermittent headache and recurrent ischemic stroke.The cerebrospinal fluid analyses showed mild pleocytosis in 2 patients and an elevated level of protein in all patients.Cerebrospinal fluid cytology revealed activated lymphocytes,suggesting the existence of aseptic meningitis.In the literature review,up to 9 cases presenting with FD and aseptic meningitis were found,which bore a resemblance to our patients in demographic and clinical characteristics.Conclusion Our cases suggested that aseptic meningitis in FD might be under-detected and easily misdiagnosed,and should be more thoroughly examined in further cases.

Association between large artery stenosis,cerebral small vessel disease and risk of ischemic stroke

We aimed to assess the associations of large artery stenosis(LAS)and cerebral small vessel disease(CSVD)with the risk of ischemic stroke and to investigate their respective and combined contributions.In the prospective population-based Shunyi Study,1,082 stroke-free participants aged 55.9±9.1 years were included.Participants were followed for incident stroke throughout the study period(2013-2019).Total small vessel disease score was used to measure CSVD burden.Cervico-cerebral large artery stenosis was evaluated via brain magnetic resonance angiography and carotid ultrasound.We estimated the risk of ischemic stroke in relation to LAS and CSVD with Cox regression models.During a mean follow-up of 4.2 years,34 participants(3.1%)experienced at least one ischemic stroke.Severe LAS(≥50% stenosis versus no stenosis:HR=3.27(95%CI:1.31-8.18))and high CSVD burden(total small vessel disease score 2-4 versus 0 point:HR=12.73(4.83-33.53))were associated with increased stroke risk independently.In multivariate models,CSVD burden(7.72%)explained a larger portion of the variation in stroke risk than severity of LAS(3.49%).Our findings identified that both LAS and CSVD were associated with future ischemic stroke in asymptomatic subjects,while those with high CSVD burden deserve more attention in primary prevention of stroke.

Inflammatory biomarkers and cerebral small vessel disease:a community-based cohort study

Background and purpose Although inflammation has been proposed to be a candidate risk factor for cerebral small vessel disease(CSVD),previous findings remain largely inconclusive and vary according to disease status and study designs.The present study aimed to investigate possible associations between inflammatory biomarkers and MRI markers of CSVD.Methods A group of 15 serum inflammatory biomarkers representing a variety of those putatively involved in the inflammatory cascade was grouped and assessed in a cross-sectional study involving 960 stroke-free subjects.The biomarker panel was grouped as follows:systemic inflammation(high-sensitivity C reactive protein(hsCRP),interleukin 6 and tumour necrosis factorα),endothelial-related inflammation(E-selectin,P-selectin,intercellular adhesion molecule 1,vascular cell adhesion molecule 1(VCAM-1),CD40 ligand,lipoprotein-associated phospholipase A2,chitinase-3-like 1 protein and total homocysteine(tHCY))and media-related inflammation(matrix metalloproteinases 2,3 and 9,and osteopontin).The association(s)between different inflammatory groups and white matter hyperintensity(WMH),lacunes,cerebral microbleeds(CMBs),enlarged perivascular space(PVS)and the number of deep medullary veins(DMVs)were investigated.Results High levels of serum endothelial-related inflammatory biomarkers were associated with both increased WMH volume(R^(2)=0.435,p=0.015)and the presence of lacunes(R^(2)=0.254,p=0.027).Backward stepwise elimination of individual inflammatory biomarkers for endothelial-related biomarkers revealed that VCAM-1 was significant for WMH(β=0.063,p=0.005)and tHCY was significant for lacunes(β=0.069,p<0.001).There was no association between any group of inflammatory biomarkers and CMBs or PVS.Systemic inflammatory biomarkers were associated with fewer DMVs(R^(2)=0.032,p=0.006),and backward stepwise elimination of individual systemic-related inflammatory biomarkers revealed that hsCRP(β=−0.162,p=0.007)was significant.Conclusion WMH and lacunes were associated with endothelial-related inflammatory biomarkers,and fewer DMVs were associated with systemic inflammation,thus suggesting different underlying inflammatory processes and mechanisms.

Automated quantification of Ki-67 index associates with pathologic grade of pulmonary neuroendocrine tumors

Background: Classification of the pulmonary neuroendocrine tumor (pNET) categories is a step-wise process identified by presence of necrosis and number of mitoses per 2 mm^2. In neuroendocrine tumor pathology, Ki-67 was first described as a prognostic factor in the pancreas and incorporated into the grading system of digestive tract neuroendocrine neoplasms in the 2010 WHO classification. However, the significance of Ki-67 in pNETs was still a controversial issue. This study was to investigate the potentially diagnostic value of Ki-67 in pNETs. Methods: We retrieved 159 surgical specimens of pNETs, including 35 typical carcinoids (TCs), 2 atypical carcinoid (ACs), 28 largecell neuroendocrine carcinomas (LCNECs), 94 small-cell lung cancers (SCLCs). Manual conventional method (MCM) and computer-assisted image analysis method (CIAM) were used to calculate the Ki-67 proliferative index. In CIAM, 6 equivalent fields lly annotated for digital image analysis. Results: The Ki-67 index among the 4 groups with ranges of 0.38% to 12.66% for TC, 4.34% to 29.48% for AC, 30.67% to 93.74% for LCNEC, and 40.71% to 96.87% for SCLC. The cutoff value of Ki-67 index to distinguish low grade with high grade was 30.07%. For the univariate survival analyses in pNETs, both the overall survival and progression-free survival correlated with Ki-67 index. In addition, the Ki-67 index performed by CIAM was proved to be of great positive correlation with MCM.(500 ×500 μm) at 10× magnification were manua Conclusions: Ki-67 index counted by CIAM is a reliable method and can be a useful adjunct to classify the low- and high-grade NETs.

HTRA1-related autosomal dominant cerebral small vessel disease

Background:Homozygous or compound heterozygous mutations in high temperature requirement serine peptidase A1(HTRA1)gene are responsible for cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy(CARASIL).Recently,increasing evidence has shown that heterozygous HTRA1 mutations are also associated with cerebral small vessel disease(CSVD)with an autosomal dominant pattern of inheritance.This study was aimed to analyze the genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD.Methods:We presented three new Chinese cases of familial CSVD with heterozygous HTRA1 mutations and reviewed all clinical case reports and articles on HTRA1-related autosomal dominant CSVD included in PUBMED by the end of March 1,2020.CARASIL probands with genetic diagnosis reported to date were also reviewed.The genetic and clinical characteristics of HTRA1-related autosomal dominant CSVD were summarized and analyzed by comparing with CARASIL.Results:Forty-four HTRA1-related autosomal dominant CSVD probands and 22 CARASIL probands were included.Compared with typical CARASIL,HTRA1-related autosomal dominant probands has a higher proportion of vascular risk factors(P<0.001),a later onset age(P<0.001),and a relatively slower clinical progression.Alopecia and spondylosis can be observed,but less than those in the typical CARASIL.Thirty-five heterozygous mutations in HTRA1 were reported,most of which were missense mutations.Amino acids located close to amino acids 250-300 were most frequently affected,followed by these located near 150∼200.While amino acids 250∼300 were also the most frequently affected region in CARASIL patients,fewer mutations precede the 200th amino acids were detected,especially in the Kazal-type serine protease domain.Conclusions:HTRA1-related autosomal dominant CSVD is present as a mild phenotype of CARASIL.The trend of regional concentration of mutation sites may be related to the concentration of key sites in these regions which are responsible for pathogenesis of HTRA1-related autosomal dominant CSVD.