Pancreatic Tumor-Targeting Stemsome Therapeutics.

Owing to the intrinsic ability of stem cells to target the tumor environment, stem-cell-membrane-functionalized nanocarriers can target and load active anticancer drugs. In this work, a strategy that focuses on stem cells that self-target pancreatic cancer cells is developed. In particular, malignant deep tumors such as pancreatic cancer cells, one of the intractable tumors that currently have no successful clinical strategy, are available for targeting and destruction. By gaining the targeting ability of stem cells against pancreatic tumor cells, stem cell membranes can encapsulate nano-polylactide-co-glycolide loaded with doxorubicin to target and reduce deep pancreatic tumor tissues. Considering the lack of known target proteins on pancreatic tumor cells, the suggested platform technology can be utilized for targeting any malignant tumors in which surface target receptors are unavailable.

Prognostic model in patients with metastatic urothelial carcinoma receiving immune checkpoint inhibitors after platinum failure.

Immune checkpoint inhibitors (ICIs) have become a standard treatment for metastatic urothelial carcinoma (mUC) after platinum-based chemotherapy. However, the prognostic factors for patients with mUC receiving ICIs are not well established. We retrospectively collected clinical and laboratory data and reviewed the survival outcomes of patients with mUC who were treated with ICIs after platinum-based chemotherapy. We used univariate and multivariable Cox proportional hazard models to identify independent prognostic factors, and the concordance index (C-index) to evaluate the performance of the new prognostic model. In addition, bootstrap analysis was employed for internal validation of the prognostic model. A total of 224 patients were included in the study. With a median follow-up of 10.5 months (interquartile range, 5.1-17.4 months), median overall survival (OS) was 13.6 months (95% confidence interval [CI], 9.7-17.3 months). In multivariable analysis, independent prognostic factors predicting adverse OS were the presence of liver metastasis (LM), hypoalbuminemia, and neutrophil-lymphocyte ratio (NLR) >5. When patients were categorized into 3 risk groups, median OS was not reached (NR) (95% CI, 17.3-NR), 9.5 months (6.8-NR), and 2.9 months (2.3-4.4) for patients with a score of 0, 1, and 2+, respectively. The C-index for the new model was 0.763 (95% CI, 0.739-0.787). A novel prognostic model, including LM, hypoalbuminemia, and NLR, was developed and validated to estimate OS in patients with platinum-refractory disease on second- or subsequent-line ICI therapy. Further investigations, including prospective validation, are needed.

Efficacy and Safety of Trastuzumab Biosimilar (CT-P6) Compared With Reference Trastuzumab in Patients With HER2-positive Advanced Gastric Cancer: A Retrospective Analysis.

OBJECTIVES: Treatment with trastuzumab and chemotherapy significantly improves the outcome in patients with human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). CT-P6 (trastuzumab-pkrb; Herzuma) is a trastuzumab biosimilar approved for the treatment of HER2-positive gastric cancer. In this study, we aimed to compare the efficacy and safety of CT-P6 and reference trastuzumab as first-line treatment for HER2-positive AGC. MATERIALS AND METHODS: The medical records of 102 patients with HER2-positive AGC treated with first-line trastuzumab-based chemotherapy were retrospectively reviewed. These patients were treated with either reference trastuzumab (n=72) or a biosimilar (n=30). Treatment outcomes, such as objective response rate, progression-free survival (PFS), and overall survival (OS), were compared between the reference and biosimilar groups. RESULTS: The objective response rate of both groups (52.8% and 56.8% in the reference and biosimilar groups, respectively) were comparable (P=0.72). No statistically significant difference was observed with the reference versus biosimilar trastuzumab for PFS (median PFS, 6.9 vs. 5.4 mo; P=0.98) or OS (median OS, 12.3 mo vs. not reached; P=0.42). Safety profiles were similar between the 2 groups. CONCLUSIONS: Biosimilar trastuzumab showed equivalent outcome to reference trastuzumab, with similar adverse events. Biosimilar trastuzumab can suitably and safely replace trastuzumab as a reference for the treatment of HER2-positive AGC.

Resistance and aerobic exercise intervention during chemotherapy in patients with metastatic cancer: a pilot study in South Korea.

BACKGROUND: We investigated the feasibility and safety of an exercise intervention in patients with metastatic solid cancer. METHODS: Patients scheduled to receive first-line chemotherapy for metastatic cancer with a life expectancy of ≥4 months, no brain metastases, and no high risk of fracture were recruited to participate in a 12-week, combined resistance and aerobic exercise program consisting of supervised, hospital-based (2×/week) and home-based training (3×/week) during palliative chemotherapy. Feasibility and safety of the exercise intervention were the primary outcomes. The secondary outcomes were skeletal muscle mass and strength, functional capacity, quality of life (QoL), and fatigue. RESULTS: Nineteen patients were enrolled in this pilot study. Five patients withdrew consent before the exercise intervention due to fear of exacerbating cancer-related symptoms (n=2), transportation issues (n=2), and unknown reasons (n=1). Ten patients (71.4%) completed the 12-week exercise program. Mean attendance rate of the supervised exercise sessions was 64.9% (range, 16.7-95.8%). No adverse events or skeletal complications occurred during the supervised exercise sessions. Among participants, there were no significant changes in muscle area at the third lumbar level (mean change =-0.7 cm2, P=0.869) or appendicular skeletal muscle mass (mean change =0.1 kg, P=0.661). The overall QoL assessed using the Functional Assessment of Cancer Therapy-General significantly improved post-exercise interventions (P=0.037). There were significant improvements in the QoL subdomains of emotional well-being and physical, social, and cognitive functions. CONCLUSIONS: Exercise interventions are feasible and safe in patients with metastatic cancer. Exercise interventions can improve QoL and prevent skeletal muscle loss during palliative chemotherapy.

Noncanonical immune response to the inhibition of DNA methylation by Staufen1 via stabilization of endogenous retrovirus RNAs.

DNA-methyltransferase inhibitors (DNMTis), such as azacitidine and decitabine, are used clinically to treat myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Decitabine activates the transcription of endogenous retroviruses (ERVs), which can induce immune response by acting as cellular double-stranded RNAs (dsRNAs). Yet, the posttranscriptional regulation of ERV dsRNAs remains uninvestigated. Here, we find that the viral mimicry and subsequent cell death in response to decitabine require the dsRNA-binding protein Staufen1 (Stau1). We show that Stau1 directly binds to ERV RNAs and stabilizes them in a genome-wide manner. Furthermore, Stau1-mediated stabilization requires a long noncoding RNA TINCR, which enhances the interaction between Stau1 and ERV RNAs. Analysis of a clinical patient cohort reveals that MDS and AML patients with lower Stau1 and TINCR expressions exhibit inferior treatment outcomes to DNMTi therapy. Overall, our study reveals the posttranscriptional regulatory mechanism of ERVs and identifies the Stau1-TINCR complex as a potential target for predicting the efficacy of DNMTis and other drugs that rely on dsRNAs.

Predictive Roles of HER2 Gene Amplification and Neutrophil-to-Lymphocyte Ratio on Survival in HER2-Positive Advanced Gastric Cancer Treated With Trastuzumab-Based Chemotherapy.

OBJECTIVES: Trastuzumab is used as an agent against human epidermal growth factor receptor 2 (HER2)-positive advanced gastric cancer (AGC). The aim of this study was to determine how HER2 gene amplification and neutrophil-to-lymphocyte ratio (NLR) could predict long-term survival in AGC patients that underwent trastuzumab-based chemotherapy. METHODS: We retrospectively reviewed medical records of 112 patients between 28 and 91 years old (median of 66 y) with AGC treated with first-line trastuzumab-based chemotherapy. The level of HER2 gene amplification was determined by the HER2/centromere enumerator probe 17 (CEP17) ratio and HER2 gene copy number (GCN). NLR was calculated as the neutrophil count divided by the lymphocyte counts. RESULTS: Median HER2/CEP17 ratio, HER2 GCN, and NLR values were 2.85, 7.1, and 2.81, respectively. Objective response rate in both high HER2/CEP17 ratio (59.4% vs. 28.1%, P=0.012) and HER2 GCN groups (62.1% vs. 33.3%, P=0.032) was higher than that of each group. High NLR correlated with significantly worse median overall survival (OS) (median OS, 8.2 vs. 18.9 mo, P=0.002) and progression free survival (PFS) (median PFS: 5.1 vs. 8.0 mo, P=0.005). However, median OS and PFS were not significantly different according to HER2/CEP17 ratio or HER2 GCN. In the multivariate analysis, high NLR, Eastern Cooperative Group performance status, and poorly differentiated/signet ring cell type were independent factors for OS. CONCLUSIONS: NLR was a significant predictor of long-term survival in AGC patients treated with first-line trastuzumab-based chemotherapy. Future validation of prospective trials with larger patient populations will be needed.

Portal vein stent for symptomatic malignant portal vein stenosis: A single-center experience.

OBJECTIVE: Malignant tumors around the portal vein (PV) can cause PV stenosis, and PV stent (PVS) placement may reduce symptoms. This study aimed to investigate the efficacy and safety of PVS for symptomatic malignant PV stenosis. METHODS: Fourteen consecutive patients who underwent percutaneous transhepatic PVS placement from January 2016 to August 2018 for symptomatic malignant PV stenosis were included. Medical records were retrospectively reviewed for procedure-related complications, symptom relief, and stent patency duration after PVS. RESULTS: Of 14 patients, 7 (50%) were men (median age, 67.5 [range 32-76] years). The most common primary cancer site was the pancreas (57%). PVS placement and complete stent expansion were successful in 13 (93%) patients. PV stenosis-related symptoms were resolved in most patients, 13 of 14 (93%). There was a significant decline in median PV pressure gradient across the stenotic lesions. Postprocedural complications included 1 case (7%) each of hemothorax, intrahepatic PV thrombosis, and liver abscess. With a median follow-up of 114 (range 25-260) days, stent occlusion occurred in 5 patients (36%). The median stent patency duration was 201 days, and the overall survival was 117 days. CONCLUSIONS: PVS placement is a safe and effective method for relieving the symptom of of malignant PV stenosis.

Arterial stiffness and functional outcome in acute ischemic stroke.

OBJECTIVE: Arterial stiffness is a common change associated with aging and can be evaluated by measuring pulse wave velocity (PWV) between sites in the arterial tree, with the stiffer artery having the higher PWV. Arterial stiffness is associated with the risk of stroke in the general population and of fatal stroke in hypertensive patients. This study is to clarify whether PWV value predicts functional outcome of acute ischemic stroke. METHODS: ONE HUNDRED PATIENTS WERE ENROLLED WITH A DIAGNOSIS OF ACUTE ISCHEMIC STROKE AND CATEGORIZED INTO TWO GROUPS: large-artery atherosclerosis (LAAS) or small vessel disease (SVD) subtype of Trial of Org 10172 in Acute Stroke Treatment (TOAST) classification. Each group was divided into two sub-groups based on the functional outcome of acute ischemic stroke, indicated by modified Rankin Scale (mRS) at discharge. Poor functional outcome group was defined as a mRS ≥ 3 at discharge. Student's t-test or Mann-Whitney U-test were used to compare maximal brachial-ankle PWV (baPWV) values. RESULTS: Twenty-four patients whose state was inadequate to assess baPWV or mRS were excluded. There were 38 patients with good functional outcome (mRS < 3) and 38 patients with poor functional outcome (mRS ≥ 3). The baPWV values were significantly higher in patients with poor outcome (2,070.05 ± 518.37 cm/s) compared with those with good outcome (1,838.63 ± 436.65) (p = 0.039). In patients with SVD subtype, there was a significant difference of baPWV values between groups (2,163.18 ± 412.71 vs. 1,789.80 ± 421.91, p = 0.022), while there was no significant difference of baPWV among patients with LAAS subtype (2,071.76 ± 618.42 vs. 1,878.00 ± 365.35, p = 0.579). CONCLUSIONS: Arterial stiffness indicated by baPWV is associated with the functional outcome of acute ischemic stroke. This finding suggests that measurement of baPWV predicts functional outcome in patients with stroke especially those whose TOAST classification was confirmed as SVD subtype.

Agenesis of bilateral internal carotid artery associated with basilar artery fenestration mimicking intra-arterial thrombus: a case report.

Bilateral internal carotid artery agenesis is a very rare congenital anomaly, which may be accompanied by various types of associated vascular abnormalities, included intracranial aneurysms or dolichoectatic change of posterior circulation. In this article, we present unique, and to the best of our knowledge, the first case of bilateral internal carotid agenesis associated with basilar artery fenestration, which resembles intra-arterial floating thrombus.