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Soft-tissue sarcomas (STS), with over 100 different histologic subtypes, are rare tumors that account for 1% of all adult malignancies. Immune checkpoint inhibitors (ICIs) display certain benefits in some subtypes, especially in undifferentiated pleomorphic sarcoma (UPS), alveolar soft part sarcoma (ASPS), and leiomyosarcoma (LMS). However, efficacy is difficult to predict. High tumor mutational burden (TMB-H) and programmed death-ligand 1 (PD-L1) expression are the strongest features associated with the efficacy of immunotherapy, although they are rarely found in STS patients. Until now, whether or not PD-L1 expression and TMB are related to the efficacy of immunotherapy has not been determined. In this study, we report data obtained from two STS patients, one ASPS and one UPS with a high TMB, that benefited from anlotinib combined with toripalimab following resistance to anlotinib monotherapy. A 26 year-old female patient was diagnosed with ASPS. PD-L1 was negative. Next generation sequencing (NSG) revealed ASPSCR1-TFE3 fusion and TMB-H. Following eight months of anlotinib monotherapy, the patient's disease progressed but continued to benefit from subsequent use of anlotinib combined with toripalimab for 19 months. Another 63 year-old male patient was diagnosed with UPS. PD-L1 was positive and NGS revealed TMB-H. Following 19 months of anlotinib monotherapy, the patient's disease progressed but continued to benefit from subsequent use of anlotinib combined with toripalimab. DFS is 23 months to follow-up time. The results presented are the first to report the relationship between TMB and the efficacy of immunotherapy in STS. Based on our results, we hypothesis that anlotinib combined with toripalimab is effective for the treatment of some advanced ASPS or UPS. TMB may be a potential predictive biomarker for ICI treatment and deserves additional study. [ABSTRACT FROM AUTHOR]

Human epidermal growth factor receptor2 (HER2) overexpression/amplification is associated with high malignancy, rapid disease progression and poor overall survival in breast cancer. The application of anti-HER2 drugs has greatly improved the survival of patients with HER2-positive breast cancer, but drug resistance issues affect the long-term efficacy. The HER2 mutation is considered to be one of the reasons for resistance to anti-HER2 therapy, and there is currently no standard treatment. We report for the first time the detection of HER2 amplification with R157W mutation by second-generation sequencing (NGS) in a 57-year-old hormone receptor-negative, HER2-positive woman with advanced breast cancer who was resistant to multi-line anti-HER2 therapies. She subsequently received pyrotinib combined with capecitabine treatment and achieved partial response. The small-molecule pan-HER family irreversible inhibitor pyrotinib combined with capecitabine has shown a promising effect in the treatment of HER2 mutation-induced resistance, but the molecular mechanism and efficacy need to be further verified. [ABSTRACT FROM AUTHOR]

Identification oncogenes is fundamental to revealing the molecular basis of cancer. Here, we found that FOXP2 is overexpressed in human prostate cancer cells and prostate tumors, but its expression is absent in normal prostate epithelial cells and low in benign prostatic hyperplasia. FOXP2 is a FOX transcription factor family member and tightly associated with vocal development. To date, little is known regarding the link of FOXP2 to prostate cancer. We observed that high FOXP2 expression and frequent amplification are significantly associated with high Gleason score. Ectopic expression of FOXP2 induces malignant transformation of mouse NIH3T3 fibroblasts and human prostate epithelial cell RWPE-1. Conversely, FOXP2 knockdown suppresses the proliferation of prostate cancer cells. Transgenic overexpression of FOXP2 in the mouse prostate causes prostatic intraepithelial neoplasia. Overexpression of FOXP2 aberrantly activates oncogenic MET signaling and inhibition of MET signaling effectively reverts the FOXP2 -induced oncogenic phenotype. CUT&Tag assay identified FOXP2-binding sites located in MET and its associated gene HGF . Additionally, the novel recurrent FOXP2-CPED1 fusion identified in prostate tumors results in high expression of truncated FOXP2, which exhibit a similar capacity for malignant transformation. Together, our data indicate that FOXP2 is involved in tumorigenicity of prostate., Competing Interests: XZ, CC, DW, YX, SL, WJ, JL, YQ, JZ, YZ, PW, QH, LZ, WZ, XY, LP, RQ, YL, FW, RY, ZY, JW, YZ No competing interests declared, (© 2023, Zhu et al.)

Inflammatory myofibroblastic tumor (IMT), a rare sarcoma, is primarily treated via resection of the mass. However, there is no standard treatment for recurrence or unresectable tumors. Almost 50% of IMTs carry ALK gene rearrangement that can be treated using ALK inhibitors, but therapeutic options for ALK-negative tumors are limited. This report describes a woman aged 22 years with unresectable ALK-negative IMT. Next-generation sequencing revealed a TFG-ROS1 fusion, and she had a partial response to the ROS1 inhibitor ceritinib. This report provides the first published demonstration of a patient with IMT with ROS1 fusion successfully treated using ceritinib. Our study suggests that targeting ROS1 fusions using the small molecule inhibitor shows promise as an effective therapy in patients with IMT carrying this genetic alteration, but this requires further investigation in large clinical trials.

Introduction: Although acupuncture has been recommended for alleviating cancer pain by clinical guidelines, the level of the supporting evidence needs to be improved. A pragmatic randomised controlled trial (pRCT) in a hospital setting would provide real-world assessments of the overall clinical effects of acupuncture. This pilot trial aims to explore the feasibility and provide data for sample size calculations for a pRCT evaluating the effectiveness of acupuncture as an adjunctive therapy to routine medical care for cancer pain., Methods and Analysis: Thirty patients with cancer admitted to the oncology department with moderate or severe pain will be recruited. Participants will be randomised at a ratio of 1:1 to the adjunctive acupuncture group or a control group which receives routine pain management without acupuncture. The standardised section of the acupuncture protocol will be developed based on the results of reviews of the literature, recommendations in clinical guidelines and interviews with clinical experts. The acupuncturist will be allowed to tailor the protocol according to the individual situation of each participant. Primary outcomes relevant to the feasibility of conducting a fully powered trial include: numbers and proportions of participants recruited, screened, consented and randomised; numbers and reasons for withdrawals and dropouts; numbers and types of adverse events; feasibility of implementing the trial procedures; evaluation of the comprehensiveness and ease-of-use of the case report form. Secondary outcomes are clinical measurements of the effectiveness of the treatment that are intended for use in the full-scale trial. Analysis of feasibility will be descriptive and pain intensity measures will be analysed using mixed-effects regression., Ethics and Dissemination: Ethics approval was obtained from the Institutional Ethics Committee of Guangdong Provincial Hospital of Chinese Medicine (approval no: Z2017-184-01) and RMIT University Human Research Ethics Committee (reference no: 21361). Results will be disseminated in a peer-reviewed journal, and trial participants will be informed via email and/or phone calls., Trial Registration Number: ChiCTR1800017023., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

BACKGROUND Pim-3 kinase is a highly homologous serine/threonine kinase that is overexpressed in hematological malignancies and solid tumors. Few studies have been conducted to define the role of Pim-3 in solid tumors, especially in prostate cancer. The aim of this study was to define the role of Pim-3 in development and prognosis of prostate cancer. MATERIAL AND METHODS We collected specimens from 160 patients with prostate cancer, as well as 100 patients with benign prostatic hyperplasia. Realtime polymerase chain reaction was used for the assessment of Pim-3 expression at the RNA level and Western blot was used to quantify the Pim-3 protein synthesis in 3 different cell lines. RESULTS We found that Pim-3 mRNA expression in prostate cancer tissue was significantly higher than that in benign prostatic hyperplasia tissue (p<0.05). Accordingly, the protein level expression of Pim-3 in prostate cancer cell lines was also significantly higher than that in control cells. In addition, the expression status of Pim-3 mRNA was significantly associated with pathological parameters such as pre-surgery prostate specific antigen, Gleason score, pathological stage, and lymphoid metastasis. High expression of Pim-3 also significantly decreased the survival rate of patients after surgery. CONCLUSIONS Pim-3 expression is an important risk factor for prostate cancer; we are the first team to report Pim-3 as a valuable biomarker in Chinese., Competing Interests: None.

Objective: To study the baseline distribution of polymorphisms in the promoter of peroxisome proliferators activated receptor co-activator 1 (PPARGC1A) gene in ethnic Hans from Beijing, and to assess their association with type 2 diabetes (T2DM)., Methods: A 2-stage study was designed. Firstly, the promoter region of PPAGC1A gene was screened with PCRRFLP in a small population (n=216, T2DM/control: 104/112), which was followed by a replication study of a larger group (n=1546, T2DM/control: 732/814). Fasting plasma glucose, insulin, blood lipid, height, weight, waist circumference, and blood pressure were measured in all subjects. Potential association was assessed by logistic regression. Linkage disequilibrium and haplotype analysis were conducted with Haploview software., Results: Five polymorphisms were identified with Sanger sequencing, among which T-2120C (rs3755857), -1999C/G (rs2946386) and -1437T/C (rs2970870) were included for genotypic analysis based on their moderate levels of heterozygosity. No significant difference was found between the two groups. When adjusted for age and gender confounding, we have combined the OR values from population 1 and population 2 based on Mantel-Haenszel fixed model, and recognized a mild contribution of C allele of -1999C/G (rs2946386) to the 1.18-fold risk of T2DM (P=0.03, OR=118). No haplotype was associated with T2DM after permutation correction., Conclusion: The C allele of -1999C/G ( rs2946386) in the promoter region of the PPARGC1A gene is mildly associated with T2DM. Variations in the promoter region of the PPARGC1A gene seem not to confer the risk of T2DM in our population.

The application of next generation sequencing (NGS) technique has a great impact on epigenetic studies. Coupled with NGS, a number of sequencing-based methodologies have been developed and applied in epigenetic studies, such as Whole Genome Bisulfite Sequencing (WGBS), Reduced Representation Bisulfite Sequencing (RRBS), Methylated DNA Immunoprecipitation Sequencing (MeDIP-seq), Chromatin Immunoprecipitation-Sequencing (ChIP-seq), TAB-seq (Tet-assisted Bisulfite Sequencing), Chromosome Conformation Capture Sequencing (3C-seq) and various of 3C-seq de-rivatives, DNase1-seq/MNase-seq/FAIRE-seqand RNA Sequencing (RNA-seq). These new techniques were used to iden-tify DNA methylation patterns and a broad range of protein/nucleic acid interactions, and to analyze chromatin conforma-tion.With these new technologies, researchers have gained a broader view and better tools to investigate the distributions and dynamic changes of epigenetic markers affected by both internal and external factors. The principles and characteristics of major applications of NGS technologies on epigenetics were summarized; and the recent advances and the future direc-tions in NGS-based epigenetic studies were further discussed.

The aim of this study was to investigate the association between haptoglobin (Hp) gene polymorphism and occurrence of type 2 diabetes mellitus (T2DM) in a northern Chinese population. We studied the association of the Hp gene polymorphism with T2DM in 584 unrelated T2DM patients and 690 control subjects with normal glucose tolerance among northern Chinese. The patients were diagnosed in accordance with the guidelines of the American Diabetes Association. The clinical characteristics of the study population were recorded, and the Hp genotype was determined. The frequencies of the genotypes in the group of T2DM patients and the controls were as follows: Hp2-2, 51.7% and 44.1%; Hp2-1, 39.7% and 45.1%; and Hp1-1, 8.6% and 10.9%, respectively. There was significant difference for the genotypic and allelic distribution between the two groups (p=0.021 and p=0.007, respectively). Even after readjusting for the confounding effects of age, gender, and body mass index, a significant effect of genotypes on T2DM was still found in the recessive model for the Hp2 allele tested (p=0.002). Those who had the Hp2-2 genotype had a significantly higher risk for T2DM than those with other genotypes (odds ratio=1.441, 95% confidence interval=1.143-1.817). The results showed that the Hp2-2 genotype is associated with increased risk of T2DM in the northern Chinese Han population.

Background: Bone morphogenetic protein 7 (BMP7) has been suggested to play a protective role against kidney injury in chronic kidney disease., Objectives: To identify the critical molecular regulators in the early stage of diabetic nephropathy, we studied the expression of BMP7 and 2 important kidney-specific markers, podocin and Tamm-Horsfall protein (THP)., Materials and Methods: A diabetic nephropathy model was established by intraperitoneally injecting streptozotocin (STZ) in male Kunming mice. Kidney weight index was used as an indicator of early renal injury. Kidney tissue from the diabetic model mice was obtained at 4, 8, and 12 weeks, and total protein was extracted to assess the expression of BMP7, podocin, and THP by western blot analysis., Results: Diabetic model mice were successfully established, and the kidney weight index of the model animals increased significantly. The expression of BMP7 was significantly downregulated, while the expression of THP was increased in the early stage of diabetic nephropathy. However, the expression of podocin did not change., Conclusions: Our observations suggested that down-regulation of BMP7 expression and up-regulation of THP expression were early events that occur prior to podocyte injury with the structure protein, podocin spoiled, which further confirmed that BMP7 is a key molecular regulator in the early stage of diabetic nephropathy.