PDZK1-interacting protein 1(PDZK1IP1) promotes subcutaneous preadipocyte proliferation in goats.

PDZK1-interacting protein 1(PDZK1IP1), also known as MAP17, is encoded by the PDZK1IP1 gene and is a membrane-associated protein. PDZK1IP1 have been proven to be a potent regulator of cancer cell proliferation. However, the role of PDZK1IP1 in regulating goat subcutaneous preadipocyte proliferation is unknown. Here, we cloned the full-length coding sequence of PDZK1IP1 gene, investigated the potential functional of PDZK1IP1 in goat subcutaneous preadipocyte proliferation by gaining or losing function in vitro. Our results indicated that goat PDZK1IP1 gene consists of 345 bp, encoding a protein of 114 amino acids containing a typical PDZK1IP1 (MAP17) super family domain. Overexpression of PDZK1IP1 significantly increased the number of EdU-positive cells and cell viability, and also upregulated mRNA expression of cell proliferation-associated genes including CCND1 and CDK2 in vitro cultured cells. Conversely, knockdown of PDZK1IP1 mediated by siRNA technique significantly inhibited subcutaneous preadipocyte proliferation and downregulated mRNA expression of cell proliferation-associated genes including CCNE1, CCND1 and CDK2. Collectively, these results suggested that PDZK1IP1 can promote proliferation of goat subcutaneous preadipocyte.

Consolidation chemotherapy with capecitabine after neoadjuvant chemoradiotherapy in high-risk patients with locally advanced rectal cancer: Propensity score study.

BACKGROUND: The effects of consolidation chemotherapy (CC) in neoadjuvant therapy in locally advanced rectal cancer (LARC) have been explored. However, the optimal neoadjuvant chemoradiotherapy (NCRT) and surgery interval, regimen, and cycles of chemotherapy remains unclear. AIM: To evaluate the effects of one to two cycles of CC with capecitabine on high-risk patients with LARC without extending NCRT and surgery interval. METHODS: We retrospectively evaluated high-risk patients with LARC, who were defined as having at least one of the following factors by magnetic resonance imaging: depth of invasion beyond the muscularis propria of more than 5 mm (cT3c-cT3d), T4, meso-rectal fascia or extramural vascular invasion positive, and treatment date between January 2015 and July 2019 in our center. Patients were divided into the CC and non-CC group according to whether they received CC (capecitabine 1000 mg/m2 twice daily from days 1 to 14 every 21 d) after NCRT. Propensity score matching (PSM) and inverse probability of treatment weight (IPTW) were used to balance the differences between the two groups. The main outcome was the complete response (CR) rate. RESULTS: A total of 265 patients were enrolled: 136 patients in the CC group and 129 patients in the non-CC group. The median interval was 70 d (range, 37-168). The CR rate was 24.3% and 16.3% (P = 0.107) in the CC and non-CC groups' original samples, respectively. After PSM and IPTW, the CR rate in the CC group was higher than that in non-CC group (27.6% vs 16.2%, P = 0.045; 25.9% vs 16.3%, P = 0.045). The median follow-up was 39.8 mo (range, 2.9-74.8), and there were no differences in 3-year non-regrowth disease-free survival nor overall survival in the original samples (73.2% vs 71.9%, P = 0.913; 92.3% vs 86.7%, P = 0.294), PSM (73.2% vs 73.5%, P = 0.865; 92.5% vs 89.3%, P = 0.612), and IPTW (73.8% vs 72.1%, P = 0.913; 92.4% vs 87.4%, P = 0.294). There was also no difference in grade 2 or higher acute toxicity during neoadjuvant therapy in the two groups (49.3% vs 53.5%, P = 0.492). CONCLUSION: One to two cycles of CC with capecitabine after NCRT was safe and increased the CR rate in high-risk LARC but failed to improve the long-term outcomes.

[Cloning and expression characteristic analysis of goat ST13 gene].

In this study, we cloned the complete sequence coding for aminoacids in protein (CDS) of goat ST13 gene, analyzed the bioinformation of it, and explored the expression pattern in different goat tissues and goat subcutaneous preadipocytes at different differentiation stages. To be specific, ST13 gene was cloned by reverse transcription PCR (RT-PCR), and the bioinformation was analyzed by online tools or software. The expression in various goat tissues and subcutaneous preadipocytes at different differentiation stages was detected by quantitative reverse transcription PCR (qRT-PCR). The results showed that the cloned goat ST13 gene was 1 380 bp, with CDS of 1 101 bp, encoding 366 amino acids. Protein prediction results showed that ST13 had 26 phosphorylation sites and that some sequences were highly hydrophilic and unstable. Moreover, ST13 was a non-transmembrane and non-secretory protein. Subcellular localization demonstrated that ST13 was mostly distributed in the nucleus (69.6%). Phylogeny analysis suggested that goat ST13 had the highest identity to sheep ST13. Tissue expression pattern showed that ST13 gene expressed in all of the collected 13 tissues of goat, including heart, liver, spleen, lung and kidney, especially in triceps brachii and subcutaneous fat (P < 0.01) and that the expression among heart, liver, spleen, lung, kidney, large intestine, small intestine and pancreas was insignificantly different (P > 0.05). In addition, according to the temporal expression pattern in adipocytes, the expression of ST13 was up-regulated in differentiated adipocytes, and the expression was the highest at the 108th hour of induction, significantly higher than that at other time points (P < 0.01). In conclusion, this gene expresses in various tissues of goat and regulates the differentiation of goat subcutaneous adipocytes.

One to Two Cycles of Consolidation Chemotherapy With Capecitabine After Neoadjuvant Chemoradiotherapy Does Not Benefit Low-Risk Patients With Locally Advanced Middle-Low Rectal Cancer.

BACKGROUND AND OBJECTIVE: Organ preservation can enable locally advanced rectal cancer (LARC) patients with clinical complete response (cCR) after neoadjuvant treatment to maintain quality of life. In this study, we aimed to evaluate whether one or two cycles of capecitabine after neoadjuvant chemoradiotherapy (NCRT) without extending the interval between the end of NCRT and surgery could increase the complete response (CR) rate in low-risk middle-low LARC patients. MATERIAL AND METHODS: We retrospectively evaluated middle-low LARC patients with low risk defined as clinical T2-3b, mesorectal fascia-clear, and extramural vascular invasion-negative by magnetic resonance imaging (MRI), treated between January 2015 and July 2019. Patients were divided into two groups according to whether consolidation chemotherapy was administered after NCRT. Patients in the consolidation chemotherapy group received one or two cycles of capecitabine (1000 mg/m2 twice daily from days 1 to 14). The main outcome was the CR rate, including pathological CR (pCR) and cCR. RESULTS: A total of 169 patients, 105 in the consolidation chemotherapy group and 64 in the non-consolidation chemotherapy group, were included in the study, and the median follow-up was 37.2 months (range, 0.4-71.2 months). Seventeen patients achieved cCR and the remaining 152 underwent surgery after neoadjuvant treatment. There was no significant difference in the CR rate (39.0% vs. 35.9%, p=0.686), ypT0-2N0 rate (65.2% vs. 63.3%, p=0.812), or ypN0 rate (83.7% vs. 88.3%, p=0.503) between the consolidation chemotherapy and non-consolidation chemotherapy groups. Among the patients achieved cCR, 3 (17.6%) experienced regrowth in the rectum and 2 (11.8%) experienced distant metastasis. There was also no significant difference in the 3-year disease-free survival (87.4% vs 85.9%, p=0.971) in patients who underwent surgery between the two groups. Multivariate logistic regression analysis indicated that normal Carcinoma Embryonic Antigen (CEA) levels (p = 0.001) were associated with a higher CR rate. Moreover, there were no significant differences in the incidences of grade ≥2 acute toxicities during neoadjuvant treatment. CONCLUSION: Although there was no increase in treatment-related toxicities between the two groups, simply adding one or two cycles of capecitabine after NCRT might be insufficient to benefit low-risk middle-low LARC patients.