A case report of sustained remission after radiotherapy combined with ICI in NEPC with primary drug resistance to chemotherapy.

Advanced prostate cancer (PCa) is usually treated initially with androgen deprivation therapy (ADT). Although they experience a period of disease regression, most patients progress to metastatic castration-resistant prostate cancer (mCRPC). Patients with mCRPC now have an unprecedented number of approved treatment options, including chemotherapies, hormone therapies, targeted therapies, etc. However, the improvement of overall survival (OS) in patients with mCRPC and its special subtype neuroendocrine prostate cancer (NEPC) is limited. In recent years, with the use of immune checkpoint inhibitors (ICIs), such as PD1/PDL1 and CTLA4 inhibitors, immunotherapy has once again become a promising treatment choice to stimulate antitumor immunity. However, the efficacy of NEPC receiving ICI has not been reported. Here, we describe a patient with mCRPC who developed primary resistance to current endocrine and chemotherapy regimens and progressed to mCRPC with NEPC as the main component, showing a significant and lasting response to PD1 monoclonal antibody combined with radiotherapy.

Oncogene goosecoid is transcriptionally regulated by E2F1 and correlates with disease progression in prostate cancer.

BACKGROUND: Although some well-established oncogenes are involved in cancer initiation and progression such as prostate cancer (PCa), the long tail of cancer genes remains to be defined. Goosecoid (GSC) has been implicated in cancer development. However, the comprehensive biological role of GSC in pan-cancer, specifically in PCa, remains unexplored. The aim of this study was to investigate the role of GSC in PCa development. METHODS: We performed a systematic bioinformatics exploration of GSC using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, Gene Expression Omnibus, German Cancer Research Center, and our in-house cohorts. First, we evaluated the expression of GSC and its association with patient prognosis, and identified GSC-relevant genetic alterations in cancers. Further, we focused on the clinical characterization and prognostic analysis of GSC in PCa. To understand the transcriptional regulation of GSC by E2F transcription factor 1 (E2F1), we performed chromatin immunoprecipitation quantitative polymerase chain reaction (qPCR). Functional experiments were conducted to validate the effect of GSC on the tumor cellular phenotype and sensitivity to trametinib. RESULTS: GSC expression was elevated in various tumors and significantly correlated with patient prognosis. The alterations of GSC contribute to the progression of various tumors especially in PCa. Patients with PCa and high GSC expression exhibited worse progression-free survival and biochemical recurrence outcomes. Further, GSC upregulation in patients with PCa was mostly accompanied with higher Gleason score, advanced tumor stage, lymph node metastasis, and elevated prostate-specific antigen (PSA) levels. Mechanistically, the transcription factor, E2F1, stimulates GSC by binding to its promoter region. Detailed experiments further demonstrated that GSC acted as an oncogene and influenced the response of PCa cells to trametinib treatment. CONCLUSIONS: GSC was highly overexpressed and strongly correlated with patient prognosis in PCa. We found that GSC, regulated by E2F1, acted as an oncogene and impeded the therapeutic efficacy of trametinib in PCa.

The clinicopathological significance and potential function of ULK1 in colon cancer.

Uncoordinated 51-like kinase 1 (ULK1) is an essential part involved in autophagy to maintain cell viability and homeostasis. Herein, the expression levels of ULK1 in colon cancer (CC) were investigated, and its clinicopathological features and potential function were analyzed. Data of ULK1 were obtained from a public database. UCSC XENA RNAseq data were uniformly processed by using the Toil process. STRING was employed for identification of co-expression genes and development of PPI networks whose interaction scores exceeded 0.4. The level of immune cells for tumor infiltration was calculated by means of single-sample GSEA (ssGSEA) on the basis of mRNA data of CC. The ULK1 expression was upregulated compared with both paired and unpaired normal tissues. The mRNA expression of ULK1 was upregulated in CC patients with lymph node metastasis, lymphatic invasion, and pathological stages of 3 and 4. The disease-specific survival (DSS), progression-free interval (PFI), and the overall survival (OS) of patients with upregulated mRNA expression of ULK1 were drastically reduced. Functionally, any changes related to the biological process of ULK1 may be related to macroautophagy, autophagosome organization and autophagosome assembly. As a co-expressed gene (CEG), ATG101 was up-regulated in CC tissues and indicated poor survival. ULK1 is closely related to immune cells. ULK1 expression is upregulated in CC cells and upregulation of ULK1 may serve as an accurate prognostic factor, thereby providing novel intervention targets for therapy.

[Intestine lactobacilli of 1-4 months infant and characterize their biochemical properties in Chengdu City in 2015-2016].

OBJECTIVE: To collect intestinal lactobacilli in healthy infants and to characterize them biochemically for further studies. METHODS: Lactobacilli were isolated from the fecal samples collected from total 41 of 1-4 month old healthy infants with culture method by selective medium. After morphological observation and oxygen test, the isolates were tested for their abilities to use 50 carbohydrate and identified with API 50 CHL system and 16 S RNA sequencing. The isolates were also detected for their 19 enzyme activities with API ZYM system. RESULTS: A total of 71 Lactobacillus strains were successfully isolated and well identified, including L. paracasei( 42. 3%), L. gasseri( 18. 3%), L. salivarius( 14. 1%), L. brevis( 5. 6%), L. rhamnosus( 4. 2%), L. fermentum( 1. 4%), L. plantarum( 1. 4%) and other species( 12. 7%). The seven species of Lactobacillus had strong ability of utilizing carbohydrate. Except for 14 carbohydrates that could not be fermentable, 4 kinds of carbohydrates could be metabolized by all lactobacilli from the seven species, and the other 31 kinds of carbohydrates were metabolized differently among species. Most lactobacilli were active on Leucine arylamidase, Galactosidase and Glucosidase, while other enzyme activities were species-specific and strains-specific. CONCLUSION: L. paracasei, L. gasseri and L. salivarius could be considered as dominant species of 1-4 months healthy infants. However, the carbohydrate utilization and enzyme activities of the fecal lactobacilli might be species and strain dependent.

[A preliminary analysis of changes in composition of intestinal microbiota during infancy using polymerase chain reaction-denaturing gradient gel electrophoresis].

OBJECTIVE: To investigate the composition of bacteria in the stools of infants and the colonization of intestinal microbiota during infancy. METHODS: Fresh stools were collected from 15 healthy infants at 0, 2, 4, 7, 10, 14, and 28 days and 3, 6, and 12 months after birth. Polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) was used to analyze the composition of intestinal microbiota, perform sequencing of dominant bacteria, and to analyze the changes in the composition of intestinal microbiota during infancy. RESULTS: DGGE fingerprint showed that the composition of intestinal microbiota during infancy changed significantly over time after birth. The cloning and sequencing results indicated that Proteobacteria colonized the earliest, mainly the obligate aerobes Enterobacter and Pseudomonas, followed by the obligate anaerobes (Clostridium hathewayi and Veillonella parvula) and the facultative anaerobe Clostridium ramosum in Firmicutes, and Verrucomicrobia. Actinobacteria colonized the latest, mainly Bifidobacterium, and gradually became dominant bacteria. CONCLUSIONS: During infancy, obligate aerobes colonize the intestinal tract the earliest, followed by obligate anaerobes and facultative anaerobes. Proteobacteria colonizes the earliest, followed by Firmicutes and Verrucomicrobia, and Actinobacteria, mainly Bifidobacterium, colonizes the latest.