Computed tomography-based nomogram of Siewert type Ⅱ/Ⅲ adenocarcinoma of esophagogastric junction to predict response to docetaxel, oxaliplatin and S-1

BACKGROUND Neoadjuvant chemotherapy(NAC)has become the standard care for advanced adenocarcinoma of esophagogastric junction(AEG),although a part of the patients cannot benefit from NAC.There are no models based on baseline computed tomography(CT)to predict response of Siewert type II or III AEG to NAC with docetaxel,oxaliplatin and S-1(DOS).AIM To develop a CT-based nomogram to predict response of Siewert type II/III AEG to NAC with DOS.METHODS One hundred and twenty-eight consecutive patients with confirmed Siewert type II/III AEG underwent CT before and after three cycles of NAC with DOS,and were randomly and consecutively assigned to the training cohort(TC)(n=94)and the validation cohort(VC)(n=34).Therapeutic effect was assessed by disease-control rate and progressive disease according to the Response Evaluation Criteria in Solid Tumors(version 1.1)criteria.Possible prognostic factors associated with responses after DOS treatment including Siewert classification,gross tumor volume(GTV),and cT and cN stages were evaluated using pretherapeutic CT data in addition to sex and age.Univariate and multivariate analyses of CT and clinical features in the TC were performed to determine independent factors associated with response to DOS.A nomogram was established based on independent factors to predict the response.The predictive performance of the nomogram was evaluated by Concordance index(C-index),calibration and receiver operating characteristics curve in the TC and VC.RESULTS Univariate analysis showed that Siewert type(52/55 vs 29/39,P=0.005),pretherapeutic cT stage(57/62 vs 24/32,P=0.028),GTV(47.3±27.4 vs 73.2±54.3,P=0.040)were significantly associated with response to DOS in the TC.Multivariate analysis of the TC also showed that the pretherapeutic cT stage,GTV and Siewert type were independent predictive factors related to response to DOS(odds ratio=4.631,1.027 and 7.639,respectively;all P<0.05).The nomogram developed with these independent factors showed an excellent performance to predict response to DOS in the TC and VC(C-index:0.838 and 0.824),with area under the receiver operating characteristic curve of 0.838 and 0.824,respectively.The calibration curves showed that the practical and predicted response to DOS effectively coincided.CONCLUSION A novel nomogram developed with pretherapeutic cT stage,GTV and Siewert type predicted the response of Siewert type II/III AEG to NAC with DOS.

Germline promoter hypermethylation of tumor suppressor genes in gastric cancer

AIM: To explore germline hypermethylation of the tumor suppressor genes MLH1, CDH1 and P16INK4a in suspected cases of hereditary gastric cancer (GC). METHODS: A group of 140 Chinese GC patients in whom the primary cancer had developed before the age of 60 or who had a familial history of cancer were screened for germline hypermethylation of the MLH1, CDH1 and P16INK4a tumor suppressor genes. GenomicDNA was extracted from peripheral blood leukocytes and modified by sodium bisulfite. The treated DNA was then subjected to bisulfi te DNA sequencing for a specif ic region of the MLH1 promoter. The methylation status of CDH1 or P16INK4a was assayed using methylation-specif ic PCR. Clonal bisulf ite allelic sequencing in positive samples was performed to obtain a comprehensive analysis of the CpG island methylation status of these promoter regions. RESULTS: Methylation of the MLH1 gene promoter was detected in the peripheral blood DNA of only 1/140 (0.7%) of the GC patient group. However, this methylation pattern was mosaic rather than the allelic pattern which has previously been reported for MLH1 in hereditary non-polyposis colorectal cancer (HNPCC) patients. We found that 10% of the MLH1 alleles in the peripheral blood DNA of this patient were methylated, consistent with 20% of cells having one methylated allele. No germline promoter methylation of the CDH1 or P16INK4a genes was detected. CONCLUSION: Mosaic germline epimutation of the MLH1 gene is present in suspected hereditary GC patients in China but at a very low level. Germline epimutation of the CDH1 or P16INK4a gene is not a frequent event.

Cancer-testis Antigen OY-TES-1 Expression and Immunogenicity in Hepatocellular Carcinoma

Summary:Cancer testis(CT)antigens have received particular attention in cancer immunotherapy.OY-TES-1 is a member of CT antigens.This study was to evaluate OY-TES-1 expression and immunogenicity in hepatocelluar carcinoma(HCC).OY-TES-1 mRNA expression was detected in 56 HCC tissues and 5 normal liver tissues by reverse transcriptase PCR(RT-PCR).Of the 56 cases of HCC tissues tested,37 cases had tumor and matched adjacent non-cancer tissues and were subjected to both RT-PCR and quantitative real-time PCR.OY-TES-1 protein was subsequently observed on a panel of tissue microarrays.Sera from patients were tested for OY-TES-1 antibody by ELISA.To identify OY-TES-1 capable of inducing cellular immune response,OY-TES-1 protein was used to sensitize dentritic cells and the cytotoxicity effect was measured in vitro.The results showed that OY-TES-1 mRNA was highly expressed in 41 of the 56(73.21%)HCC tissues,whereas none in 5 normal liver tissues.OY-TES-1 mRNA was frequently expressed not only in HCC tissues(72.97%,27/37),but also in paired adjacent non-cancer tissues(64.86%,24/37).But the mean expression level of OY-TES-1 mRNA in HCC tissues was significantly higher than that in adjacent non-cancer tissues(0.76854 vs.0.09834,P=0.021).Immunohistochemistry showed that OY-TES-1 protein expression was detected in 6 of the 49 cases of HCC tissues,and absent in 9 cases of normal liver and 6 cases of cirrhosis tissues.Seropositivity was detected in 10 of the 45 HCC patients,but not detected in 17 cirrhosis patients and 76 healthy donors.The specific cytotoxic T cells elicited by OY-TES-1 could kill HLA-A2^+HCC cell line which expressed OY-TES-1.The target lysis was mainly HLA class I-dependent and could be blocked by antibodies against monomorphic HLA class I but not HLA class II molecule.In summary,OY-TES-1 expression is upregulated in HCC tissues and can be recognized by humoral and cellular responses,which suggests that OY-TES-1 is an attractive target for tumor immunotherapy in HCC.

Rhinocerebral mucormycosis caused by Rhizopus oryzae in a patient with acute myeloid leukemia: A case report

BACKGROUND Rhinocerebral mucormycosis(RCM)is a rare fatal fungal infection which is on the increase among immunocompromised hosts such as patients who have had hematological cancers,or have received immunosuppressive drugs,corticosteroids,or other T cell suppressing agents.CASE SUMMARY We report a case of RCM caused by Rhizopus oryzae,one of the most common opportunistic pathogens,in a patient suffering from a fourth relapse of acute myeloid leukemia.The patient developed RCM after he had received long-term antibiotic agents and corticosteroids.The pathogen was isolated three times from nasal secretions collected from the deep parts of the nasal cavity and was identified by morphology and internal transcribed spacer sequencing.Blood infection was excluded by droplet digital polymerase chain reaction and blood culture.The patient was empirically treated with caspofungin and voriconazole for several days while the lesions continued to progress.The patient was given amphotericin B in combination with caspofungin after RCM was suspected,and the lesions improved over the course of treatment,which lasted several days.However,the patient eventually died of the primary disease.CONCLUSION This case indicates that immunosuppressive drugs,including corticosteroids and antimetabolites in hematological tumor,do increase the risk of infections of this type.Early diagnosis,prompt and frequent surgical debridement,and treatment with amphotericin B without delay are all essential in combatting RCM.

Adiabatic shear banding of hot-rolling Ti–6Al–4V alloy subjected to dynamic shearing and uniaxial dynamic compression

Effect of stress state including dynamic shearing and uniaxial dynamic compression on adiabatic shear banding(ASBing) of hot-rolling Ti–6Al–4V(TC4) alloy was investigated. The absorbed energy of specimen before failure was calculated to evaluate the susceptibility to adiabatic shear band(ASB) of TC4 alloy quantitatively.Results show that the susceptibility to ASB of hot-rolling TC4 alloy exhibits obvious anisotropy under both dynamic shearing and uniaxial dynamic compression conditions, but the anisotropy of susceptibility to ASB under dynamic shearing condition exhibits an opposite tendency with that under uniaxial dynamic compression condition. Under the condition of uniaxial dynamic compression, material shows the highest susceptibility to ASB when loaded along transverse direction(TD) of the hot-rolling TC4, while the lowest susceptibility when loaded along rolling direction(RD). However, under the condition of dynamic shearing,the material behaves in the opposite way, demonstrating the lowest susceptibility when loaded along TD of the hotrolling TC4, while the highest susceptibility when loaded along RD.