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Background: Liver cancer is a type of malignant tumor with high morbidity and mortality in People's Republic of China. Its occurrence and development involve the variation and expression changes of multiple genes, and the pathogenesis and related regulatory networks are complex. Purpose: In the present research, we investigate the involvement of NEAT1_2 and SFPQ in cisplatin resistance in liver cancer. The effects of LncRNA NEAT1 and SFPQ expression on the chemotherapeutic resistance of liver cancer cells were analyzed. Methods: The expression level of NEAT1_2 and SFPQ mRNA in tissue specimens or cell lines were examined by RT-qPCR and western blotting. CCK-8 assay was performed to evaluate cell viability. Cell proliferation was performed using the EdU cell proliferation assay. Results: Our data showed that increase NEAT1_2 and SFPQ expressions in liver cancer specimens were associated with the development of cisplatin resistance; high SFPQ expression level impaired patients' survival from liver cancer. Gain-and loss-of function assay using NEAT1_2 knock-in and knock-out cells constructed using CRISPER/Cas9 system revealed that NEAT1_2 is essential for liver cancer cell survival and mediates cisplatin resistance in liver cancer cells at least partially through SFPQ. Artificial change in NEAT1_2 expression level didn't significantly influence SFPQ transcription or translation level. Conclusion: Our data revealed NEAT1_2—SFPQ axis as a novel cisplatin resistance mechanism in liver cancer cells in vitro. [ABSTRACT FROM AUTHOR]

Aberrant TGFβ signaling plays critical roles in the progression of multiple cancers; however, the functional mechanism of this signaling network in the infectious milieu of Esophageal Squamous Cell Carcinoma (ESCC) remains largely unknown. In this study, by using global transcriptomic analysis, we found that Porphyromonas gingivalis infection increased TGFβ secretion and promoted the activation of TGFβ/Smad signaling in cultured cells and in clinical ESCC samples. Furthermore, we demonstrated for the first time that P. gingivalis enhanced the expression of Glycoprotein A repetitions predominant (GARP), thereby activating TGFβ/Smad signaling. Moreover, the increased GARP expression and the subsequent TGFβ activation was partially dependent on the fimbriae (FimA) of P. gingivalis . Intriguingly, eliminating P. gingivalis , inhibiting TGFβ, or silencing GARP led to a decreased phosphorylation of Smad2/3, the central mediator of TGFβ signaling, as well as an attenuated malignant phenotype of ESCC cells, indicating that the activation of TGFβ signaling could be an adverse prognostic factor of ESCC. Consistently, our clinical data demonstrated that the phosphorylation of Smad2/3 and the expression of GARP were positively correlated to the poor prognosis of ESCC patients. Lastly, using xenograft models, we found that P. gingivalis infection remarkably activated TGFβ signaling and subsequently enhanced the tumor growth and lung metastasis. Collectively, our study indicated that TGFβ/Smad signaling mediates the oncogenic function of P. gingivalis in ESCC, which is augmented by the expression of GARP. Therefore, targeting either P. gingivalis or GARP-TGFβ signaling could be a potential treatment strategy for patients with ESCC., Competing Interests: None., (AJCR Copyright © 2023.)

Multidrug resistance (MDR) is one of the main causes leading to the failure in cancer treatment. Differential proteins between esophageal squamous cell carcinoma (ESCC) cell line EC9706 and its cisdiamminedichloroplatinum (CDDP)-resistant subline EC9706/CDDP revealed by quantitative analysis may provide deeper insights into the molecular mechanisms of MDR implicated in ESCC. EC9706/CDDP was generated by exposure of its parental sensitive EC9706 to a step-wise increase of CDDP concentration during EC9706 cultivation. The stable isotope labeling with amino acids in cell culture (SILAC) was used to label EC9706 and EC9706/CDDP with heavy and light medium, separately. Mixed peptides derived from EC9706 and EC9706/CDDP were analyzed by high performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS/MS) and subsequently subjected to bioinformatics analysis to identify differential proteins between EC9706 and EC9706/CDDP. Compared to parental EC9706, EC9706/CDDP manifested phenotypes of slow proliferation, cell pleomorphology, atypia and increased resistant-index 3.23. Seventy-four differential proteins identified in the present study belongs to various families with multiple functions, such as cytoskeleton (20%), energy metabolism (11%), transcription regulation and DNA repair (11%), redox homeostasis (9.5%), protein biosynthesis and mRNA processing (12%), ribosome constituent (8.1%), molecular chaperone (8.1%), immunity/inflammation (5.4%), intracellular transport (5.4%) and nucleosome assembly (2.7%), which indicated that development of MDR is a complicated process involving dysregulation of multiple molecules and pathways. The data is of great value for in-depth elucidation of molecular mechanisms of the MDR implicated in ESCC and may represent potential molecular targets for future therapeutic development.

Esophageal cancer (EC) is one of the six most common cancers across the world. The striking 3-4: 1male predominance of esophageal squamous cell carcinoma (ESCC) has not yet been well explained. Our hypothesis is that the changes in level of estrogen and/or subtype of estrogen receptor (ER) may exert a protective factor in esophageal carcinogenesis and thus estrogen analogues may represent a promising target for prevention and treatment of ESCC. Several lines of evidence in a mouse ESCC model have suggested an inhibitory role of estrogen in ESCC growth and development. Consistent with this, our results showed that male and female counterparts from a high incidence area (HIA) for EC had significantly decreased serum estradiol compared to healthy controls from a low incidence area (LIA). Moreover, serum level of estradiol of ESCC patients from the HIA were significantly lower compared to healthy controls from both HIA and LIA. Numerous studies indicate that relatively low androgen level, high estrogen level (environmental and endogenous) and ratio alteration of sex hormones are important factors explaining decreased ESCC incidence. Both ERalpha and ERbeta are ligands to estradiol with different effects on transcription at activator protein-1 sites. Estrogen exerts a suppressive effect, mainly through ERalpha in ESCC, and an accelerative function, mainly through ERbeta. Our hypothesis suggests that administration of novel potent estrogen analogues might be an effective measure for prevention and treatment of ESCC in HIA.

Background & Objective: Our recent study on proteomics for esophageal cancer has indicated the importance of Annexin II as a promising protein to distinguish esophageal cancer patients from healthy subjects. This study was to detect the expression of Annexin II in esophageal squamous cell carcinoma (ESCC) and adjacent tissues, and to explore the role of Annexin II in ESCC pathogenesis and mechanisms., Methods: The expression of Annexin I in 33 specimens of ESCC and adjacent tissues from Linzhou, a high-incidence area for esophageal cancer in Henan province, was detected by ABC immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR)., Results: Annexin II protein was expressed in 90.6% normal esophageal epithelium and decreased with ESCC progression. In carcinoma in situ (CIS), 50.0% foci lost Annexin II protein expression. The expression of Annexin II protein was increased in well differentiated SCC and decreased with loss of differentiation of SCC. In poorly differentiated SCC, 45.4% foci lost Annexin II protein expression. However, RT-PCR did not detect differential expression of Annexin II mRNA between normal esophageal epithelium and CIS., Conclusions: Elevated or reduced expression of Annexin II may be correlated to reverse or progression of carcinogenesis respectively, and Annexin II may be another candidate biomarker for screening of high-risk subjects and early diagnosis of SCC.

Aim: To further understand the molecular basis for gastric cardia carcinogenesis and to provide etiological clues., Methods: Endoscopic mucosa biopsy and histopathological examinations were made on 37 subjects from a high incidence area for both esophageal and gastric cardia carcinomas in northern China. All the biopsy samples were fixed in 850 ml. (-1)L alcohol and embedded in paraffin. Each block contained one piece of tissue and was serially section at 5 microm. Immunohistochemistry (ABC) was carried out on these gastric cardia samples to determine the alterations of p16 and Rb., Results: Based on the histopathlogical examination there were 11 cases of chronic superficial gastritis, 12 cases of chronic atrophic gastritis and 14 cases of dysplasia. The immunostaining demonstrated different levels of unclear immunostaining of p16 and Rb in normal gastric cardia tissue and the tissues with different severity of lesions. With the lesions progressing, the positive immunostaining rates for p16 protein had a decreasing tendency. In contrast, the positive immunostaining rate for Rb protein had an increasing tendency. There was a significant negative relationship between the two parameters. Changes of p16 was CSG 11(100%), CAG 7(58%), DYS 4(29%) and changes of Rb was CSG 2(18%), CAG 8(67%) and DYS 12(86%), (P<0.05)., Conclusion: The alterations of p16 and Rb protein may play a role in the early stages of gastric cardia carcinogenesis.

Background: Esophageal cancer (EC) remains a leading cause of cancer-related deaths in Linzhou (formerly Linxian) and Huixian of Henan province, northern China, which has been well recognized as the highest incidence area for EC. The lack of useful chemoprevention agents and early detection methods is the key factors for stable EC incidence in these areas. Human esophageal carcinogensis has been considered as a multistep progressive process. The natural history for EC, however is not very clear., Methods: Follow-up studies with linear repeated biopsies and histopathological examination were performed on 778 subjects from Linzhou and Huixian. Of these subjects, 578 subjects were followed for 11 years (1989-2000), 400 subjects with different severity of esophageal precancerous lesions were randomly divided into 2 groups for intervention studies with calcium and decaffeinated green tea (DGT). Each group included 200 subjects (100 subjects for treatment, and 100 subjects for placebo). In calcium group, each subject received an oral supplementation of 1,200 mg of calcium daily for 11 months. In DGT group, each subject received 5 mg of DGT daily for 12 months. In placebo group, each subject received placebo pill for 11 months (calcium group) and 12 month (DGT group). At the entry and the end of the trial, esophageal biopsy specimens were taken at the middle and the lower thirds of the esophagus and from macroscopic lesions, if only, of each subject., Results: DGT trail did not show apparent difference between the treatment and placebo group in alleviating the esophageal precancerous lesions and abnormal cell proliferation. For the calcium intervention study, after 11 years' follow-up, 10 subjects had developed into cancers in the calcium group (10%, 8 EC and 2 GCA), and 8 subjects developed into EC in the placebo group (8%). All these patients were diagnosed at very early stage of cancer (symptom-free). Of the 578 subjects, 25 (18 males and 7 females) had developed into EC (n = 23, 4.3%) and gastric cardia cancer (GCA, n = 2, 0.3%), during the 11 years' follow-up. The mean time of cancer development (from entry of the follow-up study to the cancer detection) was 5.0 +/- 2.9 years (males) and 4.7 +/- 3.2 years (females). Of the 25 patients with EC and GCA, 11 were from the 387 followed subjects with "normal" histomorphology of biopsy at the entry of the follow-up study (3%, 11/387), 2 were from the subjects with basal cell hyperplasia, grade I (BCH I, 2%, 2/94), 7 from the subjects with BCH grade II (BCH II, 10%, 7/72), and 5 from BCH III and dysplasia (20%, 5/25)., Conclusions: DGT trail was not shown to have beneficial effects in alleviating esophageal precancerous lesions and abnormal cell proliferation patterns. Calcium supplementation did not produce apparent long-term effects on EC. BCH II could be considered as precancerous lesions of EC. The quantitative histopathological analysis in terms of number of proliferating basal cell layers is of importance in determining the high-risk subjects for EC and evaluating the intervention results. Follow-up studies with repeated endoscopic biopsies are the powerful strategy for early detection and mortality control of EC and GAC in the high incidence area.

The complete nucleotide sequence of isolate B935 of the RNAs of broad bean wilt virus2 (BBWV2) was determined. RNA1 contained 5956 nucleotide (nt) residues in length exclusive the 3' terminal poly(A)tail, and encoded a single long open reading frame (ORF) with a molecular weight of 210 063 (210 kD). RNA2 was composed of 3 601 nt residues exclusive of the poly(A) at the 3' end, and encoded a single long ORF with a molecular weight of 119 002 (119 kD). The determination of the N terminal sequences of large coat protein (LCP) and small coat protein (SCP) indicated that the polyprotein of RNA2 was cleaved at Q/G(465/466) residues and Q/A(867/868) residues, to release three mature proteins a N-terminal protein, LCP and SCP. The N-terminal protein shared homology with 58 kD/48 kD movement protein of cowpea mosaic virus and contained a similar rNTP-binding domain, indicating that this protein may have the function of movement. Comparisons between the RNA1-encoded polyprotein and proteins encoded by several species in Comoviridae revealed that the 210 kD polyprotein could be cleaved into proteins such as RdRp, protease, NTP-binding domain (NTBM), protease co-factor and Vpg. The phylogenetic tree based on the amino acid sequences of LCP and SCP confirmed that the two serotypes of BBWV should be regarded as different viruses.

The full-length cDNA of tobacco mosaic virus faba bean isolate (TMV-B) was amplified with RT-PCR in which T7 promoter sequence was added in the 5' terminus of its upstream primer, so that full-length cDNA was put directly under the control of a T7 promoter. The cDNA was cloned into plasmid pT7Blue and linear DNA was got by digesting the recombinant with KpnI or KpnI and PstI. Using these linear DNA and full-length PCR product as templates, respectively, their in vitro transcripts were inoculated to Nicotiana tabacum and Chenopodium amaranticolor. All of the transcripts had infectivity and produced symptoms similar to that of wild TMV. It was found that transcripts of the full-length PCR product had higher infectious efficiency than those of linear DNA.

AIM:To investigate the pathogenesis of gastric cardia and the distal part of stomach cancer and to further characterize the histopathogenesis model for gastric cardia cancer from the high-risk population for esophageal cancer.METHODS:Mass survey with endoscopic mucosa biopsy and histopathological examination were carried out on 226 subjects aged above 30 years. Three biopsies were collected one each from the middle part of the esophagus, the gastric cardia and the pyloric antrum. The biopsy tissue was fixed with 85% alcohol and paraffin-embedded.RESULTS:The incidence of intestinal metaplasia and dysplasia at gastric cardia epithelium was higher than that at the pyloric antrum from the subjects in the same area. And there were high incidences of both esophageal and gastric cardia cancer, but a low incidence of gastric cancer at the distal part of the stomach.CONCLUSION:There might be different etiology and pathogenesis of gastric cardia and pyloric cancer at the distal part of the stomach.