Seizure‐related 6 homolog (mouse)‐like 2 (SEZ6L2) was shown to be involved in transcription of a type 1 transmembrane protein for regulating cell fate. Until now, the expression and function of SEZ6L2 in various cancers, including colorectal cancer (CRC), were unclear. In the present study, we determined the expression of SEZ6L2 in a tissue microarray from patients with CRC and then, analysed the correlation between SEZ6L2 expression and the prognosis of the patients. Furthermore, the potential function of SEZ6L2 in CRC was determined using cell counting kit, colony formation assay and xenograft model in vitro and in vivo. Flow cytometry, Western blotting, immunohistochemical staining and a blocking experiment were employed to investigate the underlying mechanism of SEZ6L2 regulating CRC growth. Our results indicated that SEZ6L2 was significantly up‐regulated in tumour tissues of patients with CRC compared with adjacent normal tissues. Up‐regulation of SEZ6L2 was correlated with a poor prognosis in patients with CRC. In vitro experiments suggested that the knockdown of SEZ6L2 inhibits CRC cell growth and colony formation, but it has no significant impact on the invasion. The antitumour effects of shSEZ6L2 were also confirmed by a xenograft model. Investigations of the mechanisms indicated that the knockdown of SEZ6L2 impairs the growth of the CRC cells by inducing caspase‐dependent apoptosis, which was mediated by mitochondria‐related proteins. Furthermore, SEZ6L2 expression was inversely correlated with the expression of cytochrome C in malignant tissues in patients with CRC. Collectively, the present study indicates that SEZ6L2 is a potential prognosis biomarker and therapy target for CRC.
Clinical hyperthermic intraperitoneal chemotherapy (HIPEC) is regarded as a potential treatment that can prolong survival of patients with peritoneal metastases after cytoreductive surgery. However, treated tumor cells are prone to becoming heat resistant to HIPEC therapy through high expression of heat shock proteins (HSPs). Here, a carrier-free bifunctional nanoinhibitor was developed for HIPEC therapy in the management of peritoneal metastases. Self-assembly of the nanoinhibitor was formed by mixing Mn ion and epigallocatechin gallate (EGCG) in a controllable manner. Such nanoinhibitor directly inhibited HSP90 and impaired the HSP90 chaperone cycle by reduced intracellular ATP level. Additionally, heat and Mn ion synergistically induced oxidative stress and expression of caspase 1, which activated GSDMD by proteolysis and caused pyroptosis in tumor cells, triggering immunogenic inflammatory cell death and induced maturation of dendritic cells through the release of tumor antigens. This strategy to inhibit heat resistance in HIPEC presented an unprecedented paradigm for converting “cold” tumors into “hot” ones, thus significantly eradicating disseminated tumors located deep in the abdominal cavity and stimulating immune response in peritoneal metastases of a mouse model. Collectively, the nanoinhibitor effectively induced pyroptosis of colon tumor cells under heat conditions by inhibiting heat stress resistance and increasing oxidative stress, which may provide a new strategy for treatment of colorectal peritoneal metastases.
Despite its rising popularity, reports on the use of preoperative imatinib mesylate (IM) in patients with advanced gastrointestinal stromal tumor (GIST) are limited. This study aims to explore the clinical efficacy of preoperative IM in patients with primarily unresectable or metastatic/recurrent GIST. Between September 2009 and February 2014, patients with primarily unresectable or metastatic/recurrent GIST treated by a single medical team were recruited and considered for preoperative IM therapy. Re-examination was conducted regularly and abdominal enhanced CT data, blood biochemistry and responses to IM were recorded. A total of 18 patients were enrolled, including 13 with a primary tumor (7 stomach, 3 small bowel, 2 rectal and 1 pelvic tumor) and 5 with recurrent or metastatic GIST (2 with liver metastasis, 2 with anastomotic recurrence and 1 with pelvic GIST). The median follow-up time was 9.5 months (range of 3-63). The median tumor sizes before and after initiation of IM treatment were 9.1 cm and 6.0 cm (p=0.003) based on the CT findings, respectively. All patients showed a decrease in tumor burden and the median tumor size reduction was 35%. Sixteen of the 18 patients showed a partial response to IM and two possessed stable disease. Nine of the 18 patients (50%) underwent surgical resection of primary or metastatic/recurrent tumors, with a median of 7 months of IM therapy. One case each of multivisceral resection and tumor recurrence were noted. IM as a preoperative therapy is feasible and safe for unresectable or metastatic/recurrent GIST that can effectively decrease tumor size, facilitating resection.
Background/Aim: Lumbar hernia is caused by a defect in the abdominal wall. Due to its rarity, there is no established consensus on optimal treatment for lumbar hernia yet. Thus, we here investigated the clinical, surgical characteristics and outcomes of lumbar hernia by collecting 28 such patients from our hospital. Methods: Patients diagnosed with lumbar hernia from our institution between April 2011 and August 2020 were retrospectively collected in this study. Demographics, clinical characteristics and surgical information were recorded. Results: A consecutive series of 28 patients with lumbar hernia were retrospectively collected, including 13 males (46%) and 15 females (54%). The ages of the patients ranged from 5 to 79 years (median: 55 years), with a mean age of 55.6 ± 14.9 years. A total of 7 cases had a history of previous lumbar trauma or surgery. There were 11 (39%), 15 (54%) and 2 (7.1%) cases had right, left and bilateral lumbar hernia, respectively. Superior and inferior lumbar hernia were found in 25 (89%) and 3 (11%) patients. General anesthesia was adopted in 16 cases (group A), whereas 12 patients received local anesthesia (group B). Patients in the group B had a shorter hospital stay than that of the group A (3.5 ± 1.3 days vs. 7.1 ± 3.2 days, p = 0.001), as well as total hospitalization expenses between the two groups (2989 ± 1269 dollars vs. 1299 ± 229 dollars, p < 0.001). With a median follow-up duration of 45.9 months (range: 1–113 months), only 1 (3%) lumbar hernias recurred for the entire cohort. Conclusions: Lumbar hernia is a relatively rare entity, and inferior lumbar hernia is rarer. It is feasible to repair lumbar hernia under local anesthesia.