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Background Prognosis is poor for patients with malignant progression such as distant metastasis of oral squamous cell carcinoma (OSCC). Evidence indicates that miR-448 promotes the proliferation and inhibits apoptosis of OSCC cells. Therefore, we aimed to investigate the function of miR-448 to predict tumor progression and prognosis of OSCC. Methods Real-time quantitative reverse transcription PCR was used to measure miR-448 expression in 221 pairs of OSCC tissues and the corresponding noncancerous tissues. Patients were diagnosed with OSCC from 2009 through 2011 at the Tianjin Medical University Cancer Institute and Hospital. Chi-squared tests were performed to assess the associations between miR-448 expression and clinicopathological parameters. Kaplan–Meier analysis was employed to evaluate the association of overall survival (OS) and disease-free survival (DFS) with miR-448 levels. Univariate and multivariate analyses were performed using the Cox proportional hazards regression model. Results We show here that miR-448 expression was significantly up-regulated in OSCC tissues compared with noncancerous tissues (P < 0.01). High miR-448 expression was significantly associated with advanced T stage (P = 0.001), lymph node metastasis (P = 0.007) and higher TNM stage (P = 0.009). Moreover, Kaplan–Meier and univariate analyses revealed that patients with high expression of miR-448 experienced significantly shorter OS and DFS. Furthermore, multivariate analysis demonstrated that miR-448 expression was an independent prognostic factor for OS (P = 0.004) and DFS (P = 0.002). Conclusions Our present data suggests that miR-448 may play an important role in tumor progression and serves as a prognostic marker for OSCC. Further studies are required to assess the potential value of miR-448 to contribute to personalized treatment of OSCC.

The Nectin cell adhesion molecule (Nectin) family members are Ca2+‑independent immunoglobulin‑like cellular adhesion molecules (including Nectins 1‑4), involved in cell adhesion via homophilic/heterophilic interplay. In addition, the Nectin family plays a significant role in enhancing cellular viability and movement ability. In contrast to enrichment of Nectins 1‑3 in normal tissues, Nectin‑4 is particularly overexpressed in a number of tumor types, including breast, lung, urothelial, colorectal, pancreatic and ovarian cancer. Moreover, the upregulation of Nectin‑4 is an independent biomarker for overall survival in numerous cancer types. A large number of studies have revealed that high expression of Nectin‑4 is closely related to tumor occurrence and development in various cancer types, but the manner in which Nectin‑4 protein contributes to the onset and development of these malignancies is yet unknown. The present review summarizes the molecular mechanisms and functions of Nectin‑4 protein in the biological processes and current advances with regard to its expression and regulation in various cancer types.

Objective We investigated scoliosis incidence among junior high school students in Zhongshan city, Guangdong, China and the expression of miR-30e among those with scoliosis. Methods A total 41,258 students were included. From July 2015 to December 2017, all students underwent screening including routine observation of the standing and sitting posture, Adam's forward bend test, dorsal tilt angle measurement, and X-ray examination. Age, sex, height, weight, and body mass index (BMI) were recorded. Reverse transcription-quantitative polymerase chain reaction was used to assess miR-30e expression among students with scoliosis and 200 healthy students. Results Overall, 743 students were diagnosed with scoliosis, with an incidence rate of 1.80%. A total 646 (86.9%) students were diagnosed with idiopathic scoliosis, 38 (5.1%) with congenital scoliosis, and 59 (7.9%) with other scoliosis types. Compared with healthy students, height was significantly greater whereas weight and BMI were significantly lower among students with scoliosis, and expression of miR-30e was significantly lower. However, no significant difference was found in height, weight, BMI, and mean Cobb angle between high/low miR-30e groups. Conclusion The incidence rate for scoliosis was 1.80%, Compared with healthy students, those with scoliosis were taller, had lower weight and BMI, and miR-30e expression was significantly downregulated.

1049 Background: HER2 is an effective therapeutic target for breast and gastric cancer. A166 is an antibody-drug conjugate composed of a novel cytotoxic drug site-specifically conjugated to transtuzumab sequence via a stable protease-cleavable valine citrulline linker. Methods: This was a single arm, open-label, multicenter, dose escalating Phase 1 first-in-human study of A166 as monotherapy in solid tumor patients. Dose escalation and MTD identification was directed using a Bayesian logistic regression model with overdose control. The following dose levels were evaluated in this study: 0.3, 1.2, 3.6, 4.8 mg/kg. (ClinicalTrials.gov NCT03602079) Results: As of November 1, 2019 35 pts have completed the DLT evaluation period across 4 dose levels. Overall, A166 had an acceptable toxicity profile with no unexpected toxicities related to the study drug. No adverse events recorded met the protocol specified definition of a dose limiting toxicity at any studied dose level. Most frequently (≥10%) occurring TEAEs include were Keratitis, Decreased appetite, Dry eye, Vision blurred etc. Overall incidence of ophthalmic toxicities in the 3.6 mg/kg cohort was 80% and in the 4.8 mg/kg cohort it was 83%. Among the 27 patients evaluable for efficacy, best response was progression of disease in 11 patients (41%), stable disease in 9 patients (33%) and partial response in 7 patients (26%), for the total disease control rate of 59%.Responses were seen only at the dose levels of 3.6 mg/kg and 4.8 mg/kg. Conclusions: A166 demonstrated clinically meaningful efficacy in heavily pretreated patients with relapsed or refractory advanced solid cancers. The achievement of an ORR of 36% at efficacious dose levels and up to 100% in HER2 positive patients regardless of histology (2 CRC, 1 BC and 1 NSCLC) at the highest studied dose level exceed Clinical trial information: NCT03602079 .

e13007 Background: Human epidermal growth factor receptor 2 (HER2) is an effective therapeutic target for breast and gastric cancer. A166 is an antibody-drug conjugate composed of a novel cytotoxic drug (monomethyl auristatin F derivative ) site-specifically conjugated to transtuzumab sequence via a stable protease-cleavable valine citrulline linker, which has a DAR (Drug Antibody Ratio) of Better efficacy were observed in preclinical CDX and PDX studies including HER2 low expression and T-DM1 resistant models while toxicity studies demonstrated a good safety profile in cynomolgus monkey. Methods: Patients with HER2-expressing or amplified advanced solid tumors refractory to standard therapies were recruited. A modified Fibonacci 3 + 3 dose-escalation design was employed with 7 dose levels (0.1, 0.3, 0.6, 1.2, 2.4, 3.6, and 4.8 mg/kg every 3 weeks). Safety analyses included all patients. PK and antitumor activity were also assessed. Primary objectives in dose escalation are safety and tolerability and determination of maximum tolerated dose (MTD) and recommended Phase 2 dose. Results: As of October 1, 2019 among 19 patients (breast cancer, colorectal cancer and gastric cancer)treated,no one experienced dose-limiting toxicity. No maximum tolerated dose was determined until 4.8mg/kg dose level. Grade≥3 adverse event was reported for 4 patient as neutropenia、anemia、Hyponatremia and Hypophosphatemia. Notably, 36.8% (n = 7) of patients experienced dry eye, as well as corneal epitheliopathy, and 2 patients withdraw from the study due to grade 2 corneal epitheliopathy. In 3.6 and 4.8 mg/kg groups, 6 patients were evaluable for tumor response, including 3 with partial response, 2 with stable disease. A166 exposure increased with the increase of dose, and extremely low exposure of free toxin and toxin-linker conjugates were observed; t1/2 was 8.29 days at the 4.8mg/kg. Conclusions: A166 showed an acceptable safety profile and promising anti-tumor activity in patients with HER2-expressing advanced solid tumors. Clinical trial information: CTR20181301 .

TPS3659 Background: Elevated expression of trophoblast antigen 2 (TROP2) is often associated with invasion/aggression, progression, and metastasis of many different tumor types. Efficacies of anti-TROP2 ADC have been demonstrated both pre-clinically and in the clinical trials. SKB264 is being developed as a further optimized TROP2-targeting ADC with a proprietary cytotoxic, belotecan-derived payload and novel stable conjugation chemistry to achieve average DAR (Drug Antibody Ratio) of 7.4. Release of payload upon SKB264 internalization is in a TROP2 expression dependent manner. Extensive preclinical studies demonstrated antitumor activity of SKB264 in vitro, in xenograft and patient-derived xenograft (PDX) animal models. In addition, safety studies have demonstrated a good safety profile to allow SKB264 to be studied in clinical trials. Methods: SKB264-01 is a global open label multicenter study. The study is divided into 2 parts, the phase I is to determine the safety profile, define MTD and/or the RP2D, and characterize DLTs of SKB264. Dose escalation and MTD identification will be directed using a Bayesian logistic regression model (BLRM) with overdose control. The phase II is to evaluate efficacy and obtain clinical activity data of SKB264 as a monotherapeutic agent at the RP2D in each of the designated Phase II cohorts and overall (n = 16 per cohort; n = 48 for entire Phase II part). Objective response rate (ORR) will be continuously evaluated in each cohort using a Bayesian hierarchical model. TROP2 assessments will not be performed prior to enrollment but it will be assessed retrospectively. Confirmation of TROP2 expression by immunohistology or other methods is not required, but the Sponsor will request tissue specimens from archived materials for determination of TROP2 expression. The patient must have, in the judgment of the investigator, historically documented, incurable, locally advanced or metastatic cancer that are refractory to standard therapies of one of the following types: i. ovarian epithelial cancer, ii. gastric adenocarcinoma, iii. pancreatic adenocarcinoma, iv. triple negative breast cancer, v. bladder cancer. Patient will receive study drug as a single IV infusion at the prescribed dose level at each administration. Cycles will continue until disease progression or unacceptable toxicity. Adverse Events (AE) will be graded according to CTCAE V.5.0. Responses will be evaluated according to RECIST V1.1. The enrollment will began in Mar 2020 in USA sites. Clinical trial information: NCT04152499 .

BackgroudInterleukin-10(IL-10) is a multifunctional cytokine with both immunosuppressive and antiangiogenic functions. Polymorphisms in the IL-10 gene promoter genetically determine interindividual differences in IL-10 production. This study was performed to determined whether polymorphisms in the IL-10 gene promoter were associated with breast cancer in a Chinese Han population.MethodsWe genotyped 315 patients with breast cancer and 322 healthy control subjects for -1082A/G, -819T/C and -592A/C single nucleotide polymorphisms in the promoter region of the IL-10 gene by polymerase chain reactionerestriction fragment length polymorphism (PCR-RFLP).ResultsThere were no significant differences in genotype, allele, or haplotype frequencies in all three loci between patients and healthy controls. Analysis of breast cancer prognostic and predictive factors revealed that the -1082AA genotype was associated with a significantly increased risk of lymph node (LN) involvement (P= 0.041) and larger tumor size (P= 0.039) at the time of diagnosis. Furthermore, in the haplotype analysis of IL-10 gene, we found that patients carrying ATA haplotype were in higher LN involvement (p= 0.022) and higher tumor stage(p= 0.028) of breast cancer at the time of diagnosis compared with others.ConclusionsOur findings suggest that IL-10 promoter polymorphisms participate in the progression of breast cancer rather than in its initial development in Chinese Han women.