PEX13 is a potential immunotherapeutic indicator and prognostic biomarker for various tumors including PAAD.

The peroxisome serves a significant role in the occurrence and development of cancers. Specifically, the peroxisomal biogenesis factor 13 (PEX13) is crucial to the occurrence of peroxisomes. However, the biological function of PEX13 in cancers remains unclear. To address this, various portals and databases such as The Cancer Genome Atlas Program, The Genotype-Tissue Expression project, the Gene Expression Profiling Interactive Analysis 2, cBioPortal, the Genomic Identification of Significant Targets In Cancer 2.0, Tumor Immune Estimation Resource 2, SangerBox, LinkedOmics, DAVID and STRING were applied to extract and analyze PEX13 data in tumors. The correlations between PEX13 and prognosis, genetic alterations, PEX13-related gene enrichment analysis, weighted gene co-expression network analysis (WGCNA), protein interaction, long non-coding (lnc)RNA/circular (circ)RNA-micro (mi)RNA network and tumor immunity were explored in various tumors. The lncRNA-miRNA-PEX13 and circRNA-miRNA-PEX13 regulatory networks were identified via miRabel, miRDB, TargetScan and ENCORI portals and Cytoscape tool. In vitro assays were applied to verify the biological functions of PEX13 in pancreatic adenocarcinoma (PAAD) cells. The findings revealed that PEX13 is upregulated in various tumors and high PEX13 mRNA expression is associated with poor prognosis in patients with multiple cancers. Genetic alterations in PEX13 such as amplification, mutation and deep deletion have been found in multiple cancers. PEX13-related genes were associated with T cell receptor, signaling pathway and hippo signaling pathway through 'biological process' subontology of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses. Through WGCNA analysis, it was discovered that PEX13 hub genes were mainly enriched in the Rap1, ErbB and AMPK signaling pathways in PAAD. Immune analysis showed that PEX13 was significantly related to tumor infiltration immune cells, immune checkpoint genes, microsatellite instability, TMB and tumor purity in a variety of tumors. Cell Counting Kit-8, wound healing, Transwell and colony formation assays displayed that PEX13 knockdown could suppress PAAD cell proliferation, migration, invasion, and colony formation in vitro, respectively. Overall, PEX13 is a potential predictor of immunotherapeutic and prognostic biomarkers in various malignant tumors, including ACC, KICH, LGG, LIHC and PAAD.

PD-1 inhibitor treatment in a penile cancer patient with MMR/MSI status heterogeneity: A case report.

Penile cancer is a rare malignant disease. Paclitaxel combined with platinum is often used as a first-line chemotherapeutic regimen for late-stage penile cancer, and there is no standard second-line treatment. Clinical trials of immunotherapy for penile cancer are ongoing. There are no reports on PD1 inhibitor treatment in metastatic penile carcinoma patients with MMR/MSI status heterogeneity. A 68-year-old patient was hospitalized with bilateral inguinal lymph node metastasis and local penile recurrence after penile cancer surgery. The lesion of the right inguinal lymph node showed a mismatch-repair-deficient (dMMR)/microsatellite instability-low (MSI-L) status. After 3 cycles of sintilimab (a PD1 inhibitor) combined with paclitaxel and cisplatin, the partial response of the tumor was evaluated. Subsequently, sintilimab monotherapy was used as maintenance treatment for 2 months. However, The lesion of local penile recurrence showed mismatch repair proficient (pMMR)/microsatellite stability (MSS) status by secondary biopsy when progressed rapidly. Interestingly, after continued treatment with sintilimab combined with gemcitabine, the patient achieved a partial response again. We should be aware of the importance of secondary biopsy for different lesions to confirm the heterogeneity of MMR/MSI status. For penile cancer patients with MMR/MSI status heterogeneity, PD1 inhibitors combined with chemotherapy are safe and effective. Due to oligometastatic lesion progression caused only by the heterogeneity of MMR/MSI status, PD1 inhibitor cross-line therapy can also be considered an appropriate treatment.

Long-term survival after immunotherapy and targeted therapy without chemotherapy in an elderly patient with HER2-positive gastroesophageal junction cancer: A case report.

A 74-yr-old man underwent thoracic laparoscopy combined with radical gastrectomy, and the postoperative pathological diagnosis was esophageal and gastric cardia cancer pT3N1M0, pStage IIB. Immunohistochemical staining for HER2 (3+) and PD-L1 (<5%) was positive. Adjuvant chemotherapy was not performed because the patient developed severe thrombocytopenia (platelet counts <30 × 109/L), which was never cured throughout the reporting period. At 10.7 months post-surgery, he suffered metastases in multiple organs, including the peritoneum, liver, lung, and bone. Following two cycles of first-line trastuzumab and pembrolizumab (200 mg), he developed immune-related myositis (G2), myocarditis (G2), and hepatitis (G1). Therefore, pembrolizumab was discontinued. Trastuzumab was administered as a monotherapy; meanwhile, adoptive cytokine-induced killer (CIK) cell infusions were initiated. Eight months after the initial immunotherapy, a solitary brain metastasis was detected, and the patient underwent CyberKnife radiosurgery. For second-line therapy, adoptive CIK cell immunotherapy plus trastuzumab was still used. At the time of reporting, the patient had achieved a complete response (CR) in the brain and liver and a partial response (PR) in the ilium, and he had been followed-up for 36.6 months, much longer than the median survival time for patients with advanced GEJ cancer. We suggest that HER2-targeted therapy and immunotherapy with pembrolizumab or CIK adoptive cell infusions prolonged the overall survival of an elderly patient with HER2-positive GEJ cancer with multiple metastases.

HER2-targeted advanced metastatic gastric/gastroesophageal junction adenocarcinoma: treatment landscape and future perspectives.

Recently, the global incidence of gastric/gastroesophageal junction (G/GEJ) cancer has remained high. China is also a large country with a high gastric cancer (GC) incidence rate, where the cases of GC account for 40% of all cases worldwide. More than 90% of GEJ cancers are the adenocarcinoma pathological type. Patients with early-stage G/GEJ adenocarcinoma may have a better prognosis after surgery. In contrast, patients with advanced metastatic G/GEJ adenocarcinoma usually choose comprehensive treatment based on systemic pharmacotherapy, but the subsequent long-term survival is not optimistic. The discovery of various biomarkers, especially microsatellite instability (MSI), programmed cell death-ligand 1 (PD-L1), human epidermal growth factor receptor 2 (HER2), tumor mutational burden (TMB) and Epstein-Barr virus (EBV), has led to the identification of an increasing number of targeted populations and has greatly improved the clinical efficacy of treatments for G/GEJ adenocarcinoma. The ToGA trial added trastuzumab to standard chemotherapy, showed improved survival of patients with HER2-positive advanced G/GEJ adenocarcinoma and brought these patients into a new era of HER2-targeted therapy. Moreover, many HER2-targeted agents have been developed and studied in patients with advanced HER2-positive G/GEJ adenocarcinoma who have demonstrated excellent clinical outcomes. However, many patients experience disease progression with HER2-targeted therapy; hence, new anti-HER2 drugs keep being developed, significantly reducing HER2 resistance. This paper reviews HER2-targeted drugs for advanced metastatic G/GEJ adenocarcinoma, potential resistance mechanisms and future directions.

The clinical application value of phase angle of six parts in nutritional evaluation of tumor patients.

OBJECTIVES: The purpose of this study was to explore the clinical application value of phase angle (PA) of six parts in the nutritional evaluation and construct a prediction model for diagnosing malnutrition of tumor patients. METHODS: A total of 1129 patients with malignant tumors were analyzed retrospectively. The age, sex, tumor location and body mass index (BMI) of the patients were collected, and PA of six parts was measured. The Patient Subjective Global Assessment (PG-SGA) was used to evaluate the nutritional status of each patient. RESULTS: According to the PG-SGA, 66.5% (n = 750) of the patients were evaluated as malnourished. Patients under the age of 65 had higher PA values. The PA value of men was higher than that of women (except PA-RL). In different disease groups, the PA-RA and PA-TR values were significantly different. In our study, PA value increases with BMI and decreases with PG-SGA (except PG-SGA 0-1 group). Multivariate regression analysis indicates that the age (HR = 1.051, 95% CI 1.037-1.066, P < 0.001), BMI (HR = 0.885, 95% CI 0.849-0.924, P < 0.001), and PA-WB (HR = 0.615, 95% CI 0.546-0.692, P < 0.001) were independent significant predictors associated with malnutrition. The AUC of the prediction model is 0.7631 (p < 0.001), indicating that the model including age, BMI, and PA-WB has certain diagnostic value for the diagnosis of malnutrition. CONCLUSION: The PA-WB is an independent prognostic factor of malnutrition. The prediction model constructed by age, BMI, and PA-WB can be used as a useful tool for nutritional evaluation of tumor patients. TRIAL REGISTRATION: Clinical Trial No.: ChiCTR2100047858.

A difficult-to-diagnose pericardial fistula.

Pericardial fistula is a rare complication. Generally, the diagnosis can be confirmed by imaging examination, but our patient was an exception. We present a 71-year-old female patient that complained of remnant gastric cancer for five months and dyspnea for seven days; the dyspnea became aggravated during the last two days. After admission, emergency thoracic computed tomography and echocardiography showed pericardial effusion, and pericardiocentesis was performed. After conventional treatment, the pericardial effusion was unchanged and no cancer cells were found in the pericardial drainage. However, the color changed from turbid to golden yellow and, finally, to green. After 20 days of repeated laboratory, imaging, and gastrointestinal contrast examinations, no cause was found. Moreover, a clinical diagnosis could not be obtained following numerous comprehensive clinical analyses. Given the color change of the pericardial drainage, we strongly suspected pericardial fistula, but the imaging examinations were negative. Finally, a methylene blue test confirmed the existence of a pericardial fistula. When the color of the pericardial effusion changes, the existence of a pericardial fistula must be considered in advance, and other methods should be evaluated if imaging cannot assist in the diagnosis.

A simple assessment model based on phase angle for malnutrition and prognosis in hospitalized cancer patients.

BACKGROUND & AIMS: Malnutrition in cancer patients is a common but under-diagnosed condition that has negative effects on clinical outcomes. The development of an easy and reliable malnutrition assessment tool is thus critical for identification and nutritional support. We aimed to develop a phase angle (PA)-based prediction model of malnutrition and evaluate it in patient prognosis. METHODS: A retrospective cohort of data consisting of demographic, clinical parameter and PA test from 702 adult hospitalized cancer patients between June 2020 to February 2021 was analysed. PAs for 6 body sites were measured by a body composition analyser. Patient-generated subjective global assessment (PG-SGA) scale was used as the diagnostic standard of nutritional status (PG-SGA ≥ 4 points defined as malnutrition). Decision tree, mean decrease accuracy of random forest, stepAIC strategy and test of generalized likelihood ratio were employed to select important variables and develop models for predicting PG-SGA binary classification (PG-SGA < 4 or ≥ 4 as a split). Survival curves were plotted by using the Kaplan-Meier method. RESULTS: In all, 490 (69.8%) patients were malnourished according to their actual PG-SGA scores. Except for age, tumor type and body mass index (BMI), PA of the left arm was found to influence malnutrition classification and incorporated in the final predictive model. The model achieved good performance with an AUC of 0.813, 75.9% sensitivity and 73.3% specificity. The actual and predicted survival curves were almost overlapped. CONCLUSION: This study provides a simple nutritional assessment tool which may be used to facilitate oncology physicians to identify cancer patients at nutritional risk and potentially implement nutritional support. CLINICAL TRIAL NO: ChiCTR2100047858.

[Application of nanocellulose in flexible sensors].

The shortage of medical resources promotes medical treatment reform, and smart healthcare is a promising strategy to solve this problem. With the development of Internet, real-time health status is expected to be monitored at home by using flexible healthcare systems, which puts forward new demands on flexible substrates for sensors. Currently, the flexible substrates are mainly traditional petroleum-based polymers, which are not renewable. As a natural polymer, cellulose, owing to its wide range of sources, convenient processing, biodegradability and so on, is an ideal alternative. In this review, the application progress of nanocellulose in flexible sensors is summarized. The structure and the modification methods of cellulose and nanocellulose are introduced at first, and then the application of nanocellulose flexible sensors in real-time medical monitoring is summarized. Finally, the advantages and future challenges of nanocellulose in the field of flexible sensors are discussed.

Biomarkers and risk factors for the early prediction of immune-related adverse events: a review.

In recent years, immunotherapy has been widely used to treat patients with malignant tumors. While immune checkpoint inhibitors (ICIs) significantly improve the prognosis of cancer patients, the incidence of immune-related adverse events (irAEs) is increasing. Not only can irAEs accumulate in multiple organ systems throughout the body, but rare adverse reactions may also occur continuously. In severe cases, irAEs can be life-threatening or even lead to death. Therefore, the early identification, diagnosis and treatment of irAEs are very important. Early identification of patients with high-risk irAEs as well as the reduction or avoidance of severe irAEs have important clinical significance. This article will review the research progress of early predictive biomarkers and risk factors for the occurrence of irAEs and propose potential future directions for follow-up research and clinical applications.

Allogenic mouse cell vaccine inhibits lung cancer progression by inhibiting angiogenesis.

Aim: This research investigated the therapeutic effect of an allogeneic mouse brain microvascular endothelial cell vaccine on lung cancer and further elucidated its potential anti-angiogenic mechanism. Materials & methods: The immune effect of the allogeneic bEnd.3 vaccine and DC vaccine loaded with bEnd.3 antigen on the subcutaneous transplantation of Lewis lung cancer (LLC) was assessed by ELISA, the CCK test and the CTL killing test. The mechanism was preliminarily revealed by immunohistochemistry and immunoblot analysis. Results: This study revealed that tumor volume was decreased (p < .01) and the survival was prolonged significantly (p < .05) by the bEnd.3 vaccine in subcutaneous LLC transplantation in the vaccine prevention group. In contrast, both tumor volume in the serum therapeutic group and survival of bEnd.3 vaccine were not significantly different from those of the control group (p > .05). Importantly, tumor volume and survival of the T lymphocyte therapeutic group were decreased and prolonged (p < .05). In addition, both tumor volume and survival of DC vaccine loaded with bEnd.3 in the vaccine prevention group were decreased and prolonged significantly (p < .01). Furthermore, bEnd.3 vaccine and DC vaccine loaded with bEnd.3 both produced the activity of killing bEnd.3 target cells in vitro.The reason may induce the immune mice to produce anti-VEGFR-II, anti-endoglin and anti-integrin αν antibodies to have an anti-angiogenesis function. Conclusion: The allogeneic mouse bEnd.3 cell vaccine can block angiogenesis and prevent the development of lung cancer transplantation tumors.

Intravenous analgesia with ultra-high-dose morphine for the treatment of headache and successful withdrawal of morphine: A case report and literature review.

RATIONALE: Pain is the fifth vital sign of human beings. Morphine is the first choice for relieving moderate to severe cancer pain. Most of the previous studies merely focused on the analgesic effect of high-dose or ultra-high-dose morphine in patients with advanced cancers but did not report any cases related to successful morphine withdrawal. PATIENT CONCERNS: A 42-year-old woman was admitted to our hospital in March 2019. DIAGNOSIS: She was diagnosed with progressive aggravation of headache for 1 month, which was meningeal metastasis of lung cancer. INTERVENTIONS: Symptomatic treatments like dehydration, hormone, intrathecal injection chemotherapy and an increased dose of osimertinib to 160 mg/day were applied but showed poor curative effects. The patient refused whole-brain radiotherapy. Pain intensity level was re-evaluated and the patient scored 9 based on numerical rating scale, which suggested that the patient suffered from severer cancerous pain. Thus, the patient started to receive morphine for treating headache. OUTCOMES: The patient's headache was alleviated after receiving high-dose morphine treatment, and she continued to undergo anti-cancer treatment. After tumor remission, the patient's morphine dose gradually decreased and eventually stopped, without any withdrawal symptoms. In addition, the quality of life of the patient was greatly improved with performance status scored 2 and limb muscle strength increased from Grade 2 to Grade 5. LESSONS: For patients with advanced cancers, the application of ultra-high-dose morphine may significantly relieve cancerous pain, improve survival and quality of life, and overcome their fear for death and desperation, which contributes to the establishment of a basis for subsequent anticancer treatments. Thus, timely effective pain management and routine anticancer treatments are the key to addressing the cancer pain problem.

MiR-1260b inhibitor enhances the chemosensitivity of colorectal cancer cells to fluorouracil by targeting PDCD4/IGF1.

Colorectal cancer (CRC) is the most common malignant tumor type and has become resistant to 5-fluorouracil (5-FU) in recent decades, which is one of the most popular therapies. Recently, microRNA (miRNA or miR) has been investigated as a potential therapeutic strategy for CRC. However, there has been little investigation of the underlying mechanism of the association between expression of miRNA and chemosensitivity. The present study aimed to investigate the effect of miR-1260b inhibitor on CRC cells, and their chemosensitivity to 5-FU, by treating them with the miR-1260b inhibitor. miR-1260b inhibitor was demonstrated to significantly promote the proliferation and invasion of the CRC cell line, HCT116, and to increase the apoptotic rate. Furthermore, it was validated that programmed cell death 4 (PDCD4) was a direct target of miR-1260b inhibitor in CRC with bioinformatics tools and a luciferase assay. Western blot analysis revealed that miR-1260b inhibitor could significantly decrease PDCD4 expression, and downregulate the expression of phosphorylated-Akt (p-Akt) and phosphorylated-extracellular-signal-regulated kinase (p-ERK). In conclusion, it was confirmed that the anti-tumor effect of the miR-1260b inhibitor was conducted by blocking the phosphorylated 3-kinase/Akt pathway as dysregulated protein expression induced by miR-1260b inhibitor was rescued by insulin-like growth factor. Notably, miR-1260b inhibitor could significantly enhanced the chemoresponse of HCT116 cells to 5-FU via reduced proliferation, increased apoptosis, and downregulation of PDCD4, p-Akt and p-ERK protein expression. In summary, the present study may provide a novel direction for future clinical therapy to enhance the chemosensitivity of tumor cells.

Role of RECK methylation in gastric cancer and its clinical significance.

AIM: To investigate the relation between RECK methylation and clinicopathological characteristics of gastric cancer patients and evaluate the role of RECK methylation in peritoneal metastasis of gastric cancer. METHODS: Methylation of RECK gene in 40 paired samples of gastric cancer and its corresponding adjacent normal mucosa, lymph nodes and peritoneal irrigation fluid was detected by methylation-specific polymerase chain reaction. RESULTS: Aberrant methylation of RECK gene was detected in 27.5% (11/40) of the adjacent normal mucosa samples, in 47.5% (19/40) of gastric cancer samples, in 57.1% (12/21) of the lymph node samples, and in 35% (14/40) of peritoneal irrigation fluid samples, respectively, with a significant difference between the adjacent normal mucosa and lymph node samples (P = 0.023). Presence of RECK methylation in the primary tumor samples was significantly correlated with tumor invasion (P = 0.023). The accuracy of RECK methylation in peritoneal lavage fluid samples for the diagnosis of peritoneal metastasis of gastric cancer was 72.5% (26/40), with a sensitivity of 66.7% (6/9) and a specificity of 74.2% (23/31). CONCLUSION: Aberrant methylation of RECK gene may provide useful information for the early diagnosis and treatment of peritoneal metastasis of gastric cancer.