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Deep marine carbonate rocks have become one of the key targets of onshore oil and gas exploration and development for reserves replacement in China. Further geological researches of such rocks may practically facilitate the sustainable, steady and smooth development of the petroleum industry in the country. Therefore, through a deep investigation into the fundamental geological conditions of deep marine carbonate reservoirs, we found higher-than-expected resource potential therein, which may uncover large oil or gas fields. The findings were reflected in four aspects. Firstly, there are two kinds of hydrocarbon kitchens which were respectively formed by conventional source rocks and liquid hydrocarbons cracking that were detained in source rocks, and both of them can provide large-scale hydrocarbons. Secondly, as controlled by the bedding and interstratal karstification, as well as the burial and hydrothermal dolomitization, effective carbonate reservoirs may be extensively developed in the deep and ultra-deep strata. Thirdly, under the coupling action of progressive burial and annealing heating, some marine source rocks could form hydrocarbon accumulations spanning important tectonic phases, and large quantity of liquid hydrocarbons could be kept in late stage, contributing to rich oil and gas in such deep marine strata. Fourthly, large-scale uplifts were formed by the stacking of multi-episodic tectonism and oil and gas could be accumulated in three modes (i.e., stratoid large-area reservoir-forming mode of karst reservoirs in the slope area of uplift, back-flow type large-area reservoir-forming mode of buried hill weathered crust karst reservoirs, and wide-range reservoir-forming mode of reef-shoal reservoirs); groups of stratigraphic and lithologic traps were widely developed in the areas of periclinal structures of paleohighs and continental margins. In conclusion, deep marine carbonate strata in China onshore contain the conditions for widely and intensively preserving hydrocarbons, so large oil or gas fields are expected.

BACKGROUND: MicroRNAs regulating mRNA expression by targeting at mRNAs is known constructive in tumor occurrence, immune escape, and metastasis. OBJECTIVE: This research aims at finding negatively regulatory miRNA-mRNA pairs in esophageal squamous cell carcinoma (ESCC). METHODS: GENE expression data of The Cancer Genome Atlas (TCGA) and GEO database were employed in differently expressed RNA and miRNA (DE-miRNAs/DE-mRNAs) screening. Function analysis was conducted with DAVID-mirPath. MiRNA-mRNA axes were identified by MiRTarBase and TarBase and verified in esophageal specimen by real-time reverse transcription polymerase chain reaction (RT-qPCR). Receiver operation characteristic (ROC) curve and Decision Curve Analysis (DCA) were applied in miRNA-mRNA pairs predictive value estimation. Interactions between miRNA-mRNA regulatory pairs and immune features were analyzed using CIBERSORT. RESULTS: Combining TCGA database, 4 miRNA and 10 mRNA GEO datasets, totally 26 DE-miRNAs (13 up and 13 down) and 114 DE-mRNAs (64 up and 50 down) were considered significant. MiRTarBase and TarBase identified 37 reverse regulation miRNA-mRNA pairs, 14 of which had been observed in esophageal tissue or cell line. Through analysis of RT-qPCR outcome, miR-106b-5p/KIAA0232 signature was chosen as characteristic pair of ESCC. ROC and DCA verified the predictive value of model containing miRNA-mRNA axis in ESCC. Via affecting mast cells, miR-106b-5p/KIAA0232 may contribute to tumor microenvironment. CONCLUSIONS: The diagnostic model of miRNA-mRNA pair in ESCC was established. Their complex role in ESCC pathogenesis especially tumor immunity was partly disclosed. [ABSTRACT FROM AUTHOR]

Strata division with well logging utilizes the abrupt changing points or regions of signals, while the changing law of the wavelet modulus maxima under different scales can exactly describe the position and modality of the changing points. Based on the idea of reconstruction of wavelet modulus maxima, the well logging data fusion method built on the multiscale edge detection principle is put forward and is applied to the quantitative demarcation of sequence stratigraphy. For case study, single logging curve and multiscale fusion curve in well A in Shengtuo Oilfield are processed by quadric spline wavelet and thereby sequence boundaries on different scales can be detected. The result shows: by demarcating sequence stratigraphic units with the multiscale fusion curve analysis, better effect could be obtained. The energy accumulation and distribution on the wavelet time-frequency graph could clearly reflect the boundaries and cycle types of parasequences and parasequence sets. All these researches provide a completely new method for the quantitative demarcation of sequence and its inner depositional features. Key words: logging curve, wavelet transform, multiscale, data fusion, sequence stratigraphy

Background: There have been several studies evaluating the prognostic significance of cell division cycle associated 5 (CDCA5). However, few reports analyzed the correlation between CDCA5 and prognosis of diverse cancers based on large clinical data. We thus comprehensively analyzed CDCA5 expression and clinical significance using The Cancer Genome Atlas (TCGA) data from 31 types of solid tumors. Methods: The expression profiles of CDCA5 were investigated across pan-cancer samples from the TCGA. Cox regression and Kaplan–Meier analysis was performed to determine CDCA5's prognostic value. CDCA5 expression was further validated by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) in lung adenocarcinoma (LUAD). Results: We found that CDCA5 was significantly overexpressed in 22 types of tumors. Up-regulated CDCA5 was significantly related to poor survival in 13 types of tumors. Furthermore, CDCA5 expression was significantly associated with immune cell infiltration. Tumor mutation burden (TMB), microsatellite instability (MSI), and immune checkpoint expression were significantly correlated with CDCA5 expression. Additional analysis of IMvigor 210 cohort validated that patients with high level of CDCA5 had superior response to anti-PD-L1 therapy. Conclusion: Our findings suggested that CDCA5 could provide prognostic information in most types of cancers and contributed to tumor immune microenvironment. [ABSTRACT FROM AUTHOR]

Background: This research explored the effects of vinorelbine combined with oxaliplatin on non-small cell lung cancer (NSCLC). Materials and Methods: NSCLC cells were treated with vinorelbine, oxaliplatin, and insulin-like growth factor-1 (IGF-1; phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway activator), and transfected with ATP-binding cassette subfamily G member 2 (ABCG2) overexpression plasmid and silenced ABCG2 (siABCG2). Cell viability was detected by cell counting kit-8 assay, cell migration and invasion by the transwell assay, and cell apoptosis by flow cytometry. Levels of ABCG2, PI3K, phosphorylation (p)-PI3K, AKT, and p-AKT were evaluated through qRT-PCR and western blot. Results: Co-treatment with vinorelbine and oxaliplatin exerted synergistic effects in suppressing the proliferation, migration, invasion, and the phosphorylation of PI3K and AKT, and inhibiting ABCG2 expression while inducing apoptosis in NSCLC cells. Overexpression of ABCG2 reversed these effects on proliferation, migration, invasion, and apoptosis, while not affecting the PI3K/AKT pathway in NSCLC cells. IGF-1 inhibited the synergistic effect of vinorelbine and oxaliplatin on the NSCLC cells. Moreover, siABCG2 reversed the effects of IGF-1 on ABCG2 expression, and other cellular functions mentioned above in NSCLC cells receiving the co-treatment. Conclusion: A combination of vinorelbine with oxaliplatin represses the proliferation, migration, and invasion of NSCLC cells, and facilitates apoptosis via inhibition of the PI3K/AKT/ABCG2 axis. [ABSTRACT FROM AUTHOR]

Background. The whole tumor microenvironment (TME) infiltration features monitored by integrated roles of different RNA N6-methyladenosine (m6A) regulators remain elusive. Our study is aimed at exploring the association between m6A modification patterns, TME cell-infiltrating levels, and patients' prognosis in stomach adenocarcinoma (STAD) patients. Methods. Consensus clustering was performed based on the integrated analyses of 17 m6A regulators and 229 m6A-related hallmark genes in STAD (The Cancer Genome Atlas (TCGA) cohort, n = 443 ; Gene Expression Omnibus (GEO) GSE57303, n = 70 , GSE62254 n = 300 , and GSE84437 n = 433). A m6ASig scoring system was calculated by the principal component analysis (PCA), and its prognostic value was validated in an independent dataset GES15459. Results. Three m6A clusters were identified among 1246 STAD patients, which had significant overall survival (OS) differences and demonstrated different TME immune cell infiltration and biological behaviors. According to the m6ASig score, which was generated from the m6A-related hallmark genes, STAD patients were divided into the high-m6ASig group (n = 585) and low-m6ASig group (n = 586). Patients in the high-m6ASig group had a notably prolonged OS and higher immune cell infiltration. Moreover, patients with higher m6ASig score were associated with higher microsatellite instability (MSI); higher PD-L1, CTLA4, and ERBB2 expressions; and greater tumor mutation burden (TMB). Patients with higher m6ASig score demonstrated a better immune response and drug sensitivity. Conclusion. Our m6ASig scoring system could characterize TME immune cell infiltration, thus predict patient's prognosis and immunotherapy and chemotherapy efficacy, offering a novel tool for the individualized therapeutic implications for STAD patients. [ABSTRACT FROM AUTHOR]

BACKGROUND: MicroRNAs (miRNAs) capable of post-transcriptionally regulating mRNA expression are essential to tumor occurrence and progression. OBJECTIVE: This study aims to find negatively regulatory miRNA-mRNA pairs in prostate adenocarcinoma (PRAD). METHODS: Combining The Cancer Genome Atlas (TCGA) RNA-Seq data with Gene Expression Omnibus (GEO) mRNA/miRNA expression profiles, differently expressed miRNA/mRNA (DE-miRNAs/DE-mRNAs) were identified. MiRNA-mRNA pairs were screened by miRTarBase and TarBase, databases collecting experimentally confirmed miRNA-mRNA pairs, and verified in 30 paired prostate specimens by real-time reverse transcription polymerase chain reaction (RT-qPCR). The diagnostic values of miRNA-mRNA pairs were measured by receiver operation characteristic (ROC) curve and Decision Curve Analysis (DCA). DAVID-mirPath database and Connectivity Map were employed in GO/KEGG analysis and compounds research. Interactions between miRNA-mRNA pairs and phenotypic features were analyzed with correlation heatmap in hiplot. RESULTS: Based on TCGA RNA-Seq data, 22 miRNA and 14 mRNA GEO datasets, 67 (20 down and 47 up) miRNAs and 351 (139 up and 212 down) mRNAs were selected. After screening from 2 databases, 8 miRNA (up)-mRNA (down) and 7 miRNA (down)-mRNA (up) pairs were identified with Pearson's correlation in TCGA. By external validation, miR-221-3p (down)/GALNT3 (up) and miR-20a-5p (up)/FRMD6 (down) were chosen. The model combing 4 signatures possessed better diagnostic value. These two miRNA-mRNA pairs were significantly connected with immune cells fraction and tumor immune microenvironment. CONCLUSIONS: The diagnostic model containing 2 negatively regulatory miRNA-mRNA pairs was established to distinguish PRADs from normal controls. [ABSTRACT FROM AUTHOR]

BACKGROUND: Several studies have demonstrated that microRNAs (miRNAs) and target mRNAs are associated with different frequencies of microsatellite instability. OBJECTIVE: The study aimed to elucidate the profiles of miRNAs and target mRNAs expression and their associations with the phenotypic hallmarks of microsatellite instability in colorectal cancers (CRC) by integrating transcriptomic, immunophenotype, methylation, mutation, and survival data. METHODS: Differentially expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs) were screened out and then the miRNA-mRNA regulatory pairs were identified through two databases. We verified that the expression levels were detected in 40 microsatellite instable (MSI) and 40 microsatellite stable (MSS) CRC samples and used the logistic regression and the Cox regression method to evaluate the diagnostic and prognostic value of negative regulatory pairs respectively. RESULTS: The best diagnostic model that combines miR-31-5p, PLAGL2, miR-361-5p, and RAB27B, which were associated with immune microenvironment, tumor mutation burden (TMB), and overall DNA methylation, could significantly predict microsatellite instability in colon tissues. MiR-31-5p and RAB27B could also predict the overall survival of MSS CRCs. CONCLUSION: This study generated a predictive model of the combination of miRNAs and mRNAs to distinguish MSI versus MSS CRCs and elaborated their potential molecular mechanisms and biological functions. [ABSTRACT FROM AUTHOR]

Abstract Background Patients with advanced or metastatic non-small cell lung cancer (NSCLC) can develop acquired resistance to epidermal growth factor receptor tyrosine kinase inhibitors (TKIs) erlotinib and gefitinib. Here, we report the successful treatment with alternating chemotherapy and TKIs of two cases of advanced NSCLC who developed resistance to TKI. Case presentation Two patients with advanced or metastatic NSCLC were treated with palliative chemotherapy followed by erlotinib/gefitinib. When TKI therapy failed, two cycles of chemotherapy were provided, which were followed by re-challenge with erlotinib or gefitinib. Conclusion NSCLC patients with acquired TKI resistance should be managed aggressively whenever possible. Subsequent chemotherapy and target treatment is one of the reasonable choices for those with an initial dramatic clinical response with erlotinib/gefitinib treatment. Further studies are warranted to substantiate the association of erlotinib /gefitinib treatment with the efficacy of NSCLC patients with acquired TKI failure.

BACKGROUND: Circulating microRNAs (miRNAs) prove to be potential non-invasive indicators of cancers. The purpose of this study is to profile serum miRNA expression in breast cancer (BC) patients to find potential biomarkers for BC diagnosis. METHODS: The miRNA expression patterns of serum samples from 216 BC patients and 214 normal control subjects were compared. A four-phase validation was conducted for biomarker identification. In the screening phase, the Exiqon miRNA qPCR panel was employed to select candidates, which were further analyzed by quantitative reverse transcriptase PCR in the following training, testing, and external validation phases. RESULTS: A 12-miRNA (let-7b-5p, miR-106a-5p, miR-19a-3p, miR-19b-3p, miR-20a-5p, miR-223-3p, miR-25-3p, miR-425-5p, miR-451a, miR-92a-3p, miR-93-5p, and miR-16-5p) panel in serum was constructed. The diagnostic performance of the panel was assessed using ROC curve analyses. The area under the curves (AUCs) were 0.952, 0.956, 0.941 and 0.950 for the four separate phases, respectively. Additionally, the expression features of the 12 miRNAs were further explored in 32 pairs of BC tumor and para-tumor tissues, and 32 pairs of serum exosomes samples from patients and healthy subjects. miR-16-5p, miR-106a-5p, miR-25-3p, miR-425-5p, and miR-93-5p were highly overexpressed and let-7b-5p was conversely downregulated in tumor tissues. Excluding miR-20a-5p and miR-223-3p, the 10 other miRNAs were all significantly upregulated in BC serum-derived exosomes. CONCLUSION: A signature consisting of 12 serum miRNAs was identified and showed potential for use in non-invasive diagnosis of BC. [ABSTRACT FROM AUTHOR]

Background: The recommended phase 2 dose (RP2D) of pamiparib, an investigational PARP1/2 inhibitor, was established as 60 mg twice daily (BID) in a first‐in‐human (FIH) study (NCT02361723). Methods: Chinese patients with advanced non‐mucinous high‐grade ovarian cancer (HGOC) or triple‐negative breast cancer (TNBC) whose disease either progressed despite standard therapy, or for which there is no standard therapy were enrolled in the dose‐escalation (DE) portion of a phase 1/2 study (NCT03333915). The primary endpoint was safety/tolerability; secondary objectives were pharmacokinetics and antitumor activity. BRCA1/2 mutation status was retrospectively evaluated. Results: Nine HGOC and six TNBC patients (N = 15; n = 4, 20 mg; n = 4, 40 mg; n = 7, 60 mg) were enrolled; as of 30 September 2019, one HGOC patient remained on treatment. Seven patients (n = 5, HGOC; n = 2, TNBC) had germline BRCA1/2 mutation (gBRCAmut); all HGOC patients were resistant/refractory to platinum. Asthenia and nausea (n = 12 each) were the most common treatment‐related adverse events (TRAEs). Decreased hemoglobin was the most common grade 3 TRAE (n = 3); no grade ≥4 AEs were observed. No dose‐limiting toxicities (DLTs) were reported. Pamiparib plasma exposure was similar to exposure observed in the FIH study after a single‐dose administration, albeit slightly higher at steady state. Among 13 RECIST‐evaluable patients, two with HGOC (gBRCAmut, n = 1) achieved a confirmed partial response and six with HGOC (gBRCAmut, n = 4) achieved stable disease; all TNBC RECIST‐evaluable patients (n = 5) reported progressive disease. Conclusions: Pamiparib was generally well tolerated in Chinese patients, with durable responses observed in patients with HGOC. Based on these results, pamiparib 60 mg BID was confirmed as the RP2D. [ABSTRACT FROM AUTHOR]

Purpose: Anlotinib is a novel oral multi-targeted receptor tyrosine kinase inhibitor, which selectively inhibits VEGFR2/3, FGFR1-4, PDGFR α/β, c-kit, and Ret. It shows antitumor effect in patients with advanced refractory solid tumors. The detailed absorption, metabolism, and excretion pathways of anlotinib have not yet been fully investigated.Methods: Six male patients were enrolled and divided into two groups. Group A (containing two patients) received 14.15 mg/80 µCi/subject [14C]-anlotinib hydrochloride. Group B (containing four patients) received 14.15 mg/120 µCi/subject [14C]-anlotinib hydrochloride. The blood, urine, and feces of all the six patients after orally administration of [14C]-anlotinib were collected. The absorption, metabolism, and excretion of [14C]-anlotinib were investigated, and the efficacy and safety of anlotinib were evaluated.Results: In plasma, the average time to peak concentration (Tmax) of total radioactivity was 4.42 h and the average peak concentration (Cmax) of total radioactivity was 18.80 ng Eq./g. The average values of AUC0-last, AUC0-∞, and MRT0-t were 4071 h.ng Eq./g, 13,555 h.ng Eq./g, and 125 h, respectively. The average recovery of total radioactivity (TRA) in urine and feces was 62.03%, accounting for 48.52% and 13.51% in feces and urine of the total dosage, respectively. The parent drug, a carboxylic metabolite (M30), and mono-oxidation products (M46/M66) were major drug-related components in human plasma. Oxidative metabolism played the major role in drug clearance in human. The major metabolic pathways include oxidative deamination to M2, mono-oxidation to M1, and the formation of M30. Adverse events occurred in five patients and severe adverse events (SAE) occurred in one. Tumor response were evaluated as stable disease (SD) in three, partial response (PR) in one, and progressive disease (PD) in one of the patients, respectively.Conclusions: Anlotinib had a good pharmacokinetic profile with rapid absorption, long half-life, and extensive hepatic metabolism. The adverse events and efficacy were as expected. [ABSTRACT FROM AUTHOR]

Long intergenic non-coding RNA for kinase activation (LINK-A) has been characterized as an oncogenic long non-coding (lnc)RNA in triple-negative breast cancer and ovarian carcinoma, but its involvement in other malignancies remains elusive. In the present study, it was determined that the plasma levels of LINK-A lncRNA and Rho-associated protein kinase 1 (ROCK1) were significantly increased in patients with pancreatic adenocarcinoma compared with those in healthy controls. The plasma levels of LINK-A lncRNA were positively correlated with the plasma levels of ROCK1 in pancreatic adenocarcinoma patients, but not in healthy controls. Silencing of LINK-A led to inhibition of pancreatic adenocarcinoma cell proliferation, migration and invasion. Simultaneous overexpression of ROCK1 attenuated the inhibitory effect of LINK-A silencing on cancer cell proliferation, migration and invasion. Overexpression of LINK-A lncRNA led to upregulation of ROCK1 expression, while overexpression of ROCK1 had no significant effect on LINK-A lncRNA expression. It may therefore be concluded that LINK-A lncRNA may have a role in pancreatic adenocarcinoma, at least in part, by promoting ROCK1 expression. [ABSTRACT FROM AUTHOR]

Background: Circulating microRNAs (miRNAs) have become reliable sources of non‐invasive biomarkers for cancer diagnosis. Identification of promising miRNA biomarkers in plasma might benefit a lot to the detection of nasopharyngeal carcinoma (NPC). Methods: The Exiqon miRNA qPCR panel was used in the screening stage to identify candidate miRNAs, which were further verified by quantitative reverse transcription polymerase chain reaction (qRT‐PCR) in the following three stages among plasma samples from 200 NPC patients and 189 healthy donors (as normal controls [NCs]). The identified miRNAs were further explored in tissue specimens (48 NPC vs 32 NCs) and plasma exosomes (32 NPC vs 32 NCs). Survival analyses were ultimately conducted by Cox regression models and Kaplan‐Meier curves using log‐rank tests. Results: We identified a 7‐miRNA signature including let‐7b‐5p, miR‐140‐3p, miR‐144‐3p, miR‐17‐5p, miR‐20a‐5p, miR‐20b‐5p, and miR‐205‐5p in plasma for NPC diagnosis after four‐stage validation. The areas under the receiver operating characteristic curve (AUCs) for the signature were 0.879, 0.884, 0.921, and 0.807 for the training, testing, external validation stage, and the combined three stages, respectively. In NPC tissues, miR‐144‐3p, miR‐17‐5p, miR‐20a‐5p, and miR‐205‐5p were consistently up‐regulated while let‐7b‐5p and miR‐140‐3p were significantly down‐regulated compared to NCs. However, none of the seven identified miRNAs were dysregulated in plasma‐derived exosomes in NPC patients. As to survival analysis, none of the seven miRNAs seemed to be associated with NPC prognosis. Conclusion: We identified a 7‐miRNA signature in plasma as promising non‐invasive biomarkers for NPC detection. [ABSTRACT FROM AUTHOR]