Estrogen receptor (ER) is a nuclear receptor and the insulin-like growth factor-I (IGF-I) receptor (IGF-IR) is a transmembrane tyrosine kinase receptor. Estrogen and IGF-I are known to have synergistic effects on the growth of breast cancer cells. Recently, non-nuclear effects of ER have been under investigation. To study the mechanism involved in this process, we have used MCF-7 breast cancer cell lines transfected with IGF-IR anti-sense cDNA (SX13, MCF-7 SX13 ) that resulted in 50% reduction of IGF-IR. In MCF-7 cells, estradiol (E2) and IGF-I induced the rapid association of ER to IGF-IR, however, the interaction was abrogated in MCF-7 SX13 cells. In addition, NWTB3 cells (NIH3T3 cells overexpressing IGF-IR) were transiently transfected with ERα, the ER-IGF-IR interaction was induced by both E2 and IGF-I. Moreover, ERα regulated the IGF-I signaling pathways through phosphorylation of ERK1/2 and Akt and the interaction of ER-IGF-IR potentiated the cell growth. Finally, E2 and IGF-I stimulated translocation of ER from the nucleus to the cytoplasm. Taken together, these findings reveal that the interaction of the ER and IGF-IR is important for the non-genomic effects of ER.

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer. It is known that hyaluronic acid (HA) binds CD44 receptors, which are overexpressed on the surface of TNBC cells. To optimize the targeting ability of HA, in this study we coated gold nanobipyramids (GBPs) with high and low molecular weight HA (380 kDa and 102 kDa), named GBPs@h-HA and GBPs@l-HA, respectively. GBPs@l-HA and GBPs@h-HA had excellent stability when dispersed in water and PBS (pH 7.4) for seven days. The HA density was calculated by the ratio of HA to GBPs@l-HA and GBPs@h-HA, which was 13.22 and 4.77, respectively. The two nanoparticles displayed good photostability, which was evaluated by their photothermal performance and similar biocompatibility. Inductively coupled plasma atomic emission spectrometry (ICP-AES) revealed superior cellular uptake of GBPs@h-HA over GBPs@l-HA. Upon 808 nm laser irradiation, the GBPs@h-HA also showed higher therapeutic efficacy than GBPs@l-HA both in vitro and in vivo. Overall, our study demonstrates that the molecular weight of HA plays an important role in the targeting ability and thus photothermal therapeutic efficacy of HA-coated gold nanobipyramids.

Neurodegenerative diseases are estimated by the World Health Organization to be the second leading cause of human death by 2050. They actually are a group of chronic neurological disorders leading to motor, cognitive and sensory impairments in both human and nonhuman species. Despite different in clinical manifestation, prevalence, risk factors, cell types injured and genes hijacked, neurodegenerative disorders are usually associated with the misfolding and aggregation of a distinct protein that accumulates in diverse cellular locations including the nucleus, cytoplasm, plasma membrane and extracellular space. Here we intend to give an overview of the characters and features of several pathogenic protein aggregates in disease brains, and introduce some general signaling pathways involved in protein homeostasis with emphasis on their puzzling roles under the degenerative conditions.

Di‑methylated lysine 9 of histone H3 (H3K9me2), regulated by histone methyltransferases, is involved in the epigenetic regulation of tumor‑associated genes. The present study aimed to evaluate whether the H3K9me2 methylation level is associated with the expression level of euchromatic histone lysine methyltransferase 2 (EHMT2) in the prognosis of gastric cancer (GC). H3K9me2 methylation level and EHMT2 expression level were detected by immunohistochemistry in 118 GC samples. The clinicopathological significance of H3K9me2 and EHMT2 in patients with GC was assessed using a paired Student's t‑test, χ2 test, Kaplan‑Meier analysis with a log‑rank test and Cox's proportional hazard analysis. Strong positive immunostaining of H3K9me2 and EHMT2 was observed in cancerous tissues compared with adjacent non‑cancerous tissues. Positive immunostaining of EHMT2 and H3K9me2 was associated with lymph node metastasis, pathological grade and tumor‑node‑metastasis stage. H3K9me2 expression level was increased in tumor tissue and associated with worse specific‑disease and disease‑free survival time. In addition, EHMT2 protein expression levels were associated with the expression levels of H3K9me2. Low expression levels of H3K9me2 and EHMT2 predicted a better prognosis of patients with GC. The survival time of patients with a high expression of H3K9me2 and/or EHMT2 was significantly shorter compared with that of the patients with a low expression of H3K9me2 and/or EHMT2. In conclusion, an overexpression pattern of H3K9me2 and/or EHMT2 may be associated with clinicopathological features of GC and may be predictor markers of progression and prognosis in patients with GC, in addition to putative therapeutic targets.

Introduction: Numerous investigations have been performed to explore candidate biomarker proteins in esophageal squamous cell carcinoma (ESCC) patients, which could predict the response to chemoradiotherapy (CRT). Here we report a patient with unresectable ESCC who had unsatisfactory effects with radiotherapy, chemotherapy and immunotherapy. We performed genetic analysis in this patient to gain insights about the cause of the rapid progression. Patient concerns: A 65-year-old man presented with food obstruction, hoarse voice and choking on drinking water for 2 months, and pain behind the breastbone for 1 month. Diagnosis: The patient was clinically diagnosed with ESCC and staged as T4N1M1 Stage IV Interventions: The patient was treated with CRT and immunotherapy. Mutational analyses through high throughput DNA sequencing methodology (next generation sequencing; NGS) was performed on the patient's blood sample. Outcomes: The tumor progressed rapidly during the treatment period, and the patient passed away only 3 months from the onset of symptoms. Conclusion: Although the role of TP53 gene and PIK3CA gene in the progression, treatment and sensitivity of esophageal cancer has been studied, the mechanism of their simultaneous appearance has not been demonstrated in relevant studies. We speculate that the reason for the rapid progression in this patient during active treatment might be related to this. Further studies are needed to validate our observations.