Allulose mitigates chronic enteritis by reducing mitochondria dysfunction via regulating cathepsin B production.

Metabolic changes have been linked to the development of inflammatory bowel disease (IBD), which includes colitis. Allulose, an endogenous bioactive monosaccharide, is vital to the synthesis of numerous compounds and metabolic processes within living organisms. Nevertheless, the precise biochemical mechanism by which allulose inhibits colitis remains unknown. Allulose is an essential and intrinsic protector of the intestinal mucosal barrier, as it maintains the integrity of tight junctions in the intestines, according to the current research. It is also important to know that there is a link between the severity of inflammatory bowel disease (IBD) and colorectal cancer (CRC), chemically-induced colitis in rodents, and lower levels of allulose in the blood. Mice with colitis, either caused by dextran sodium sulphate (DSS) or naturally occurring colitis in IL-10-/- mice, had less damage to their intestinal mucosa after being given allulose. Giving allulose to a colitis model starts a chain of reactions because it stops cathepsin B from ejecting and helps lysosomes stick together. This system effectively stops the activity of myosin light chain kinase (MLCK) when intestinal epithelial damage happens. This stops the breakdown of tight junction integrity and the start of mitochondrial dysfunction. To summarise, the study's findings have presented data that supports the advantageous impact of allulose in reducing the advancement of colitis. Its ability to stop the disruption of the intestinal barrier enables this. Therefore, allulose has potential as a medicinal supplement for treating colitis.

Pharmacist-Led Management Improves Treatment Adherence and Quality of Life in Opioid-Tolerant Patients With Cancer Pain: A Randomized Controlled Trial.

INTRODUCTION: Opioid-tolerant patients are more likely to deviate from recommended treatments and to experience inadequate analgesia than opioid-naive ones. The aim of this study was to examine whether pharmacist-led management could help improve treatment adherence and quality of life. METHODS: Eligible patients were randomized in a 1:1 ratio to control group and intervention group. The control group received routine education and support, while the intervention group received additional individualized pharmacist-led care. The primary endpoint was treatment adherence in the per-protocol analysis, as evaluated by blinded assessors. An interim analysis was planned when 30% patients completed the study. Alpha was divided into the interim analysis (0.015) and the final analysis (0.035). RESULTS: In the interim analysis (97 and 87 patients in the control and intervention groups, respectively), the primary endpoint was met. Pharmacist-led intervention significantly increased treatment adherence (93.3 vs. 79.8%; OR: 2.25; 95% CI 1.02, 4.94; P = 0.013), quality of life (0.81 ± 0.17 vs. 0.72 ± 0.25; P = 0.008), and reporting of adverse events (82.7 vs. 61.9%; OR: 1.88; 95% CI 1.16, 3.07; P = 0.004). The two groups did not differ in pain control rate (66.7 vs. 57.1%; OR: 1.25; 95% CI 0.87, 1.78; P = 0.218), breakthrough pain-free rate (66.7 vs. 61.9%; OR: 1.12; 95% CI 0.78, 1.59; P = 0.532) and pain score (1.97 ± 1.04 vs. 2.15 ± 1.24; P = 0.522). CONCLUSIONS: Pharmacist-led management improved treatment adherence, quality of life, and the reporting of adverse events in opioid-tolerant patients with cancer pain. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03455023.

Downregulation of Inhibition of Apoptosis-Stimulating Protein of p53 (iASPP) Suppresses Cisplatin-Resistant Gastric Carcinoma In Vitro.

BACKGROUND Gastric cancer (GC) with cisplatin resistance is one of the leading causes of limitations to therapy. Inhibition of apoptosis-stimulating protein of p53 (iASPP) plays a key role in GC. However, the role of iASPP in GC with cisplatin resistance remains unclear. The aim of this study was to investigate iASPP expression in GC, and the functions of iASPP in cisplatin-resistant cell lines. MATERIAL AND METHODS In this study, the expression of iASPP was investigated in normal GC patients and patients with cisplatin resistance, along with GC cell lines and cell lines with cisplatin resistance. Furthermore, knockdown of iASPP was conducted in cell lines; and cell proliferation, apoptosis rate, cell cycle distribution, and cell migration and invasion were determined through CCK8, flow cytometry, Scratch test and Transwell assay, respectively. RESULTS The expression of iASPP in GC patients with cisplatin resistance was significant higher than in the health control group. Higher expression of iASPP was detected in cisplatin-resistant cancer cell lines. Cell proliferation of SGC-7901 and MGC-803 was inhibited by transfection with siRNA, along with evaluated apoptosis rate and G1 phase retardant. Furthermore, cells viability, including migration and invasion, was suppressed post-transfection with siRNA. CONCLUSIONS iASPP induced cisplatin resistance in GC patients. Thus, knockdown of iASPP might be a novel therapeutic strategy for the treatment of GC cisplatin-resistant patients.

Genetic Variants in MTHFR Gene Predict ≥ 2 Radiation Pneumonitis in Esophageal Squamous Cell Carcinoma Patients Treated with Thoracic Radiotherapy.

Reactive oxygen species (ROS), formed as an indirect production of radiotherapy (RT), could cause DNA damage of normal tissues. Meanwhile, our body possesses the ability to restore the damage by DNA repair pathways. The imbalance between the two systems could finally result in radiation injury. Therefore, in this prospective cohort study, we explored the association of genetic variants in ROS metabolism and DNA repair pathway-related genes with radiation pneumonitis (RP). A total of 265 locally advanced esophageal squamous cell carcinoma (ESCC) patients receiving RT in Chinese Han population were enrolled. Five functional single nucleotide polymorphisms (SNPs) (rs1695 in GSTP1; rs4880 in SOD2; rs3957356 in GSTA1; and rs1801131, rs1801133 in MTHFR) were genotyped using the MassArray system, and rs1801131 was found to be a predictor of ≥ 2 RP. Our results showed that, compared with TT genotype, patients with GG/GT genotypes of rs1801131 had a notably lower risk of developing ≥ 2 RP (HR = 0.339, 95% CI = 0.137-0.839, P = 0.019). Further independent studies are required to confirm this findings.

Poorer prognosis in patients with advanced gastric squamous cell carcinoma compared with adenocarcinoma of the stomach: Case report.

RATIONALE: Primary squamous cell carcinoma (SCC) of the stomach is a rare disease. The pathogenesis and prognosis of advanced SCC remains to be elucidated. The aim of the current study was to investigate the prognosis of recurrent or metastatic SCC of the stomach. PATIENT CONCERNS: A retrospective study examined the clinical characteristics and survival outcomes of 14 patients diagnosed with recurrent or metastatic SCC of the stomach, including 7 patients followed up in the hospital and 7 patients selected from the PubMed and Chinese National Knowledge Infrastructure (CNKI) database with meta-analysis between January 2003 and January 2016. DIAGNOSES: All patients meet the following diagnoses criteria: histological diagnosis of gastric squamous cell carcinoma; the tumor must not be located in the cardia area or extend into the esophagus; presence of local relapse or distant metastases of gastric SCC in computed tomography (CT) images; and no evidence of secondary SCC in the body. Clinical pathological data and follow-up data were obtained from the medical record or case report of each patient. INTERVENTIONS: Palliative chemotherapy was administered in 14 patients diagnosed with recurrent or metastatic gastric SCC. OUTCOMES: The median age of 14 patients (10 males and 4 females) was 61 years old (range, 28-76). In total, 57% (8/14 cases) of tumors were located on the lesser curvature side of the stomach and 64% (9/14 cases) of metastatic sites were identified in the liver. All patients received systemic chemotherapy, and their median survival was 7.0 months (range, 2.0-22.3 months). LESSONS: The median survival of patients with advanced gastric SCC was shorter than the median survival (11 months) of advanced gastric adenocarcinoma, suggesting that advanced gastric SCC may have a poorer prognosis compared with adenocarcinoma of the stomach in recurrent or metastatic stage.

LncRNA PVT1 overexpression is a poor prognostic biomarker and regulates migration and invasion in small cell lung cancer.

PVT1 has been suggested as playing important roles in diverse biological processes including tumorigenesis. However, the clinical significance and biological function of PVT1 in small cell lung cancer (SCLC) is still unclear. The purpose of this study is to identify the role of PVT1 in SCLC. The expression of PVT1 was examined in SCLC tissues and cell lines through real-time PCR. Meanwhile, the relationship of PVT1 expression levels with clinical characteristics of 120 SCLC patients was analyzed. Univariate and multivariate analyses were performed to determine the association between PVT1 expression and prognosis of SCLC patient. The biological function of PVT1 on tumor cell growth and mobility were explored through MTT, colony formation, Transwell migration and invasion assays in vitro. In our results, PVT1 expression was markedly higher in SCLC tissues and cell lines than in normal lung tissues and normal bronchial epithelial cell lines (both P<0.001). High levels of PVT1 were positively associated with the status of clinical stage (Limited vs. Extensive, P<0.001), lymph node metastasis (No vs. Yes, P<0.001), and distant metastasis (No vs. Yes, P<0.001) in SCLC patients. Patients with higher PVT1 expression had a significantly poorer overall survival time than did patients with low PVT1 expression (P<0.001). Multivariate analysis showed that PVT1 overexpression was an independent prognostic indicator (P=0.024) for the survival of patients with SCLC. Knocking down PVT1 expression significantly inhibited the SCLC cell migration and invasion in vitro (both P<0.001), but has no effect on the growth of SCLC cells (both P>0.05). In conclusion, PVT1 could serve as a new biomarker and a potential therapeutic target for SCLC patients.

Synthetic treatment of intracranial peripheral primitive neuroectodermal tumor with multiple metastasis: a case report.

Ewing sarcomas (ES) and peripheral primitive neuroectodermal tumors (pPNET) are now thought to belong to the same tumor family. Ewing sarcoma family tumor (ESFT) members commonly originate in bones and soft tissues. However, a few published articles describe ESFT arising from cranial cavities. Pathologically, ES/pPNET are composed of small round cells. Unambiguous distinction between pPNET and other small round cell tumors, in particular central PNET, is of clinical significance. Definitive diagnoses of pPNET can be obtained through CD99 (MIC2 gene product) membrane positivities and molecular identifications of chromosomal rearrangements between EWS and ETS family genes. Multimodal approaches comprising surgical resections, radiotherapies, and chemotherapies are required for the treatment of ESFT. Decompressive medical measures are preferentially performed when epidural masses are compressing spinal cords. In cases of ES-induced brain herniations, emergent radiotherapies may serve as effective tools. We report a case of multiple disseminated intracranial ES/pPNET for which synthetic treatments were used.

Combination targeted therapy of VEGFR inhibitor, sorafenib, with an mTOR inhibitor, sirolimus induced a remakable response of rapid progressive Uterine PEComa.

Perivascular epithelioid cell tumor is a rare tumor. To date, there is no consensus of therapy to be recommended for unresectable disease. For a low incidence and a rarely curable disease, the finding of new therapy is essential. Here we report the first case of a patient with perivascular epithelioid cell tumor whose disease had a rapid progression after surgery and had a rapid remarkable response of combination therapy of a VEGFR inhibitor, sorafenib, with an mTOR inhibitor, sirolimus. This result may have potential to deliver a new treatment option and inhibiting the mTOR pathway combined with inhibiting the VEGF pathways may be a useful strategy for malignant PEComas.

The Clinical Research of Serum VEGF, TGF-ß1, and Endostatin in Non-small Cell Lung Cancer.

The aim of the study was to analyze the expressions of vascular endothelial growth factor (VEGF), transforming growth factor ß1 (TGF-ß1) and endostatin in non-small cell lung caner (NSCLC), and to explore their correlations with NSCLC. 80 NSCLC patients during January 2013 to June 2014 were selected. The expression levels of VEGF, TGF-ß1, and endostatin before surgeries were detected, and compared with 40 healthy individuals and 40 patients with benign pulmonary diseases. Serum VEGF, TGF-ß1, and endostatin levels were (573.6 ± 25.4) pg/mL, (36.2 ± 10.5) ng/mL, and (20.3 ± 7.8) ng/mL, respectively, in NSCLC group, which were obviously higher than those in healthy individuals and patients with benign pulmonary diseases, and the difference was statistically significant (p < 0.05); there was no statistical difference of the VEGF, TGF-ß1, and endostatin levels between the healthy individuals and patients with benign pulmonary diseases (p > 0.05), or among patients with different physiological characteristics such as gender, age, and smoking history in NSCLC group (p > 0.05). Serum VEGF, TGF-ß1, and endostatin levels also showed no statistical difference among patients with different pathological characteristics such as histological types, with or without lymphatic metastasis (p > 0.05). However, the three indicators were significantly different among patients with different TNM stages, with or without distant metastasis and different cell differentiation degrees (p < 0.05). Serum VEGF and TGF-ß1 were positively related (r = 0.479, p < 0.05), endostatin was negatively related to both VEGF and TGF-ß1 (r = -0.392, -0.354, p < 0.05 in both comparisons). The expression levels of VEGF, TGF-ß1, and endostatin significantly contributed to the poor cell differentiation in NSCLC. They had important effects on the occurrence, development, and metastasis of NSCLC, which could be applied as the indicators to predict the malignancy of NSCLC.

Primary bone lymphoma: A case report and review of the literature.

Primary lymphoma of the bone (PLB) primarily arising from the medullary cavity is an extremely rare entity, with only retrospective studies and sporadic cases reported in the literature. The current study presents one case of PLB treated with chemotherapy and radiotherapy, and a review of the literature to elucidate the optimal treatment of PLB. A 73-year-old female presented with pain in the left hip that had persisted for two months. Plain X-ray and magnetic resonance imaging of the left hip showed lytic areas involving the left innominatum. Technetium-99m radionuclide imaging showed increased tracer uptake in the ilium, acetabulum and ischium. An 18F-fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) scan showed high FDG uptake. A fine-needle aspiration biopsy of the lesion was performed, and histopathological and immunohistochemical examination confirmed a diagnosis of B-cell lymphoma. The patient received radiation therapy followed by six cycles of CHOP regimen (1,000 mg cyclophosphamide, 80 mg epirubicine and 2 mg vincristine on day one, and 100 mg prednisone on days one to five, every three weeks) and achieved a complete response, as confirmed by FDG-PET-CT. At present, the patient is in a good condition. This case is noteworthy, as it is a well-documented case in which the patient received successful treatment. This case demonstrates that PLB has an improved prognosis compared with primary lymphoma of other sites; however, combined therapy may further improve the patient outcome.

The programmed cell death 6 interacting protein insertion/deletion polymorphism is associated with non-small cell lung cancer risk in a Chinese Han population.

It has been proposed that genetic factors contribute to the susceptibility of non-small cell lung cancer (NSCLC). The programmed cell death 6 interacting protein (PDCD6IP) encodes for a protein that has been known to bind to the products of the PDCD6 gene, a required protein in apoptosis. The aim of this study is to investigate the relationship between PDCD6IP insertion/deletion (I/D) polymorphism (rs28381975) and NSCLC risk in a Chinese population. A population-based case-control study was conducted in 449 NSCLC patients and 512 cancer-free controls. The genotype of the PDCD6IP gene was determined by using a polymerase chain reaction assay. The promoter activity was analyzed by luciferase reporter assay in A549 and H1299 cells. Statistically significant difference was observed when the patients and controls were compared according to ID + II versus DD (OR = 1.72, 95 % CI 1.29-2.31, P < 0.01). The I allele was significantly associated with NSCLC risk (OR = 1.41, 95 % CI 1.18-1.69, P < 0.01). Compared to TNM stage I + II, PDCD6IP I/D polymorphism significantly increased advanced NSCLC risk (OR = 2.06, 95 % CI 1.30-3.26, P < 0.01). Promoter reporter structures carrying the I allele displayed significantly higher promoter activity than the D allele in A549 and H1299 cells (P = 0.001). The results from this study suggested that PDCD6IP I/D polymorphism was potentially related to NSCLC susceptibility in Chinese Han population.

Association of chemotherapy-induced leucopenia with treatment outcomes in advanced non-small-cell lung cancer cases receiving the NP regimen.

BACKGROUND: Chemotherapy induced leutropenia has been shown to be associated with improved treatment outcomes in selected solid tumors. We studied the association of chemotherapy induced leutropenia with treatment related outcomes in advanced non-small-cell lung cancer. METHODS: This is a prospective analysis of patients receiving chemotherapy for advanced NSCLC at the Shandong Cancer Hospital from 2005-07.The chemotherapy included cisplatin 35 mg/m2, IV on d1,2 and vinorelbine 25 mg/m2 IV on d1,8 every 21 days. Patients were stratified into three groups (A) those experiencing grades 0 leucopenia, group (B) grades 1-2 and group (C) grades 3-4. The outcomes studied were response rate (RR), disease control rate (DCR), and time to progression (TTP). RESULTS: 128 patients were studied. The RRs in groups A, B and C were 30.8%, 56.8% and 71.4%, respectively, p=0.010. The DCRs were 61.5%, 83.8% and 92.9%, respectively, p=0.009 and the median TTPs were 150 days (95%CI: 91-209), 189 days (95%CI: 181-197) and 207 days (95%CI: 172-242), p=0.009. The differences in RR and TTP were significant. In patients whose CIL kept on 10 days at least, the TTP was significantly prolonged, p=0.0213, and the same was the case for those experiencing grades 1-2 leucopenia and ECOG 0, p=0.0412. CONCLUSIONS: Occurrence of CIL correlated with RR and TTP in patients with advanced NSCLC receiving cisplatin and vinorelbine chemotherapy, especially in patients experiencing grades 1-2 leucopenia and ECOG 0, and the same for those with CIL persisting for 10 days at least. CIL could be a biological measure of drug activity and a marker of efficacy.

Value of dual-time-point FDG PET/CT for mediastinal nodal staging in non-small-cell lung cancer patients with lung comorbidity.

PURPOSE: To evaluate the efficacy of dual-time-point F-18 fluorodeoxyglucose positron emission tomography (FDG PET)/ computed tomography (CT) for mediastinal nodal staging in non-small-cell lung cancer patients with lung comorbidity. MATERIALS AND METHODS: Fifty-three pathologically proven non-small-cell lung cancer patients with pulmonary comorbidity and 49 patients as controlled group without comorbidity were enrolled. PET/CT was performed at 1-hour (whole body) post-FDG injection and repeated 2 hours (thoracic) after injection. All patients received radical surgery with system mediastinal lymph node (LN) dissection. The results of LN detection by single-time-point and dual-time-point scan were compared with the histopathologic findings. RESULTS: On a per-patient basis, in patients with pulmonary comorbidity, the sensitivity, specificity, accuracy, and positive predictive values (PPV), and negative predictive values of single-time-point scan were 87.5%, 59.5%, 67.9%, 48.3%, and 91.7%, respectively. Those values of dual-time-point scan were 93.8%, 67.6%, 75.5%, 55.6%, and 96.2%, respectively. In patients without comorbidity, dual-time-point scan was similar in those values to single-time-point. On a per-nodal station basis, the specificity, accuracy, and PPV of dual-time-point scan were better than those of single-time-point with statistically significant differences (P = 0.017, 0.002, and 0.027, respectively) in patients with pulmonary comorbidity, but the difference was not statistically significant in patients with no pulmonary comorbidity. CONCLUSIONS: Dual-time-point FDG PET/CT is more effective for mediastinal nodal staging than single-time-point in patients with pulmonary comorbidity. Dual-time-point scan was useful for diagnosis of mediastinal LN metastases in reducing the false-positive results in all patients, but improved specificity, accuracy, and PPV only in patients with pulmonary comorbidity.

Pathological and clinical characteristics of 1,248 non-Hodgkin's lymphomas from a regional cancer hospital in Shandong, China.

INTRODUCTION: Non-Hodgkin's lymphomas (NHL) in China appear to have many characteristics different from those Western countries, but clinical studies to provide details have been rare so far. METHODS: This study retrospectively analyzed the characteristics of clinical and pathological data for the 1248 NHL patients in the Shandong region of China between 2002 and 2010. RESULTS: From 2002 to 2010, the number of clinical cases of NHL increased year by year. Among the total, 64.7% were B-cell NHL, 30.3% were T-cell NHL, including: diffuse large B cell lymphoma (DLBCL) (40.9%), extranodal NK/T-cell lymphoma, nasal type (NK/T) (10.0%); peripheral T cell lymphoma, unspecified (PTL) (9.2%); follicular lymphoma (FL) (6.4%); extranodal marginal zone B cell lymphoma (MALT) (5.4%); precursor T lymphoblastic leukemia/lymphoma (T-LBL) (4.5%); and chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) (3.2%). The average age of onset was 47.7 ∓ 16.3 (18-85), and the male to female ratio was 1.57:1. Compared with Shanghai and Shanxi in China, the proportion of NK/T cell lymphoma in this region was higher. In comparison with other countries, the FL and CLL/SLL in this region were significantly lower, while the incidence of T-cell lymphoma was significantly higher than that in the United States and Europe. CONCLUSIONS: The clinical and pathological distribution of NHL in Shandong region of China is consistent with that of Asian populations, but with significant difference from the Western countries. The NK/T cell lymphoma in this region was significantly higher.