Wip1 Aggravates the Cerulein-Induced Cell Autophagy and Inflammatory Injury by Targeting STING/TBK1/IRF3 in Acute Pancreatitis

xlomafota.13 shared this article with you from Inoreader Wip1 Aggravates the Cerulein-Induced Cell Autophagy and Inflammatory Injury by Targeting STING/TBK1/IRF3 in Acute Pancreatitis Via Latest Results for Inflammation Abstract Acute pancreatitis (AP) is an inflammatory reaction of pancreatic tissue self-digestion, edema, hemorrhage, and even necrosis after the activation of pancreatic enzymes in the pancreas caused by a variety of etiologies. This study was aimed to explore the functions and mechanism of Wip1 in AP. Twenty male SD rats were randomly assigned into 2 groups (control group: saline treatment; AP group: cerulein treatment). And cerulein-treated AR42J cells were conducted as AP model in vitro. The levels of amylase were detected by using the Beckman biochemical analyzer. The levels of IFNβ and TNFα were analyzed by ELISA. The autophagosomes were observed by transmission electron microscopy. The Wip1-specific shRNAs were transfected to AR42J cells to silence the expression of Wip1. The levels of Wip1 were measured by qRT-PCR and Western blot. The levels of STING/TBK1/IRF3 and LC3 were measured by Western blot. The AP model was successfully constructed by cerulein a dministration. Wip1 was notably upregulated in AP models. Autophagy and STING pathway activation were involved in the development of AP. Wip1 inhibition counteracts the promotion effect on inflammatory response induced by cerulein in AR42J Cells. Wip1 inhibition inhibited the activity of the STING/TBK1/IRF3 and reduced LC3 levels in AP. This study preliminarily explored that Wip1 could regulate autophagy and participate in the development of AP through the STING/TBK1/IRF3 signaling pathway. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Decreased expression of TRIM3 gene predicts a poor prognosis in gastric cancer

xlomafota.13 shared this article with you from Inoreader Decreased expression of TRIM3 gene predicts a poor prognosis in gastric cancer Via Latest Results for Journal of Gastrointestinal Cancer Abstract Background/aims Tripartite motif-containing 3 (TRIM3) is a member of the TRIM protein family which is known to be involved in development of numerous tumor types. However, the prognostic role of TRIM3 in gastric cancer (GC) remained to be clarified. The aim of this study was to evaluate the expression pattern and prognostic significance of TRIM3 gene and its relationship with β-catenin, CyclinD, and BCL2 expression in patients with GC. Methods A total of 40 fresh primary gastric cancer tumors and their matched adjacent noncancerous tissues were selected from the First Affiliated Hospital of Mashhad University. Real-time quantitative RT-PCR was performed to evaluate differences in TRIM3 expression in GC and normal tissues. The correlation between TRIM3 expression level and patients' overall survival, some clinicopathological variables, and β-catenin, CyclinD, and BCL-2 genes expression level were also studied. Moreover, patients were divided in two groups according to the TRIM3 expression levels: low and high. Results Compared to noncancerous tissues, TRIM3 expression in GC tissues was significantly increased (fold change = 1.58). Kaplan–Meier survival analysis revealed a significant difference of patient survival according to TRIM3 expression status (P = 0.012). Low TRIM3 expression was associated with shorter overall survival and was an independent predictor for poor prognosis in GC patients (HR, 1.25; 95%CI, 1.02-1.60; P = 0.045). Expression of TRIM3 was negatively correlated with expression of β-catenin, BCL-2, and CyclinD as genes for proliferation, apoptosis, and the cell cycle in GC patients. Conclusions This study demonstrates that decreased level of TRIM3 mRNA expression is associated with poor prognosis in patients with gastric cancer. TRIM3 may play a protective role in gastric cancer by relieving the effects of cancer progressive genes and could be considered for further investigations as a prognostic biomarker. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Safety and tolerability of regorafenib:

xlomafota.13 shared this article with you from Inoreader Safety and tolerability of regorafenib: a real-life experience Via Latest Results for Journal of Gastrointestinal Cancer Abstract Background Regorafenib has been approved among the treatment options for patients with advanced stage colorectal cancer (CRC), hepatocellular carcinoma (HCC), and gastrointestinal stromal tumors (GIST). In this study, we aim to report the real-life experience of the safety and tolerability regorafenib in our institution. Methods We conducted a retrospective chart review of 43 patients who received regorafenib in Kuwait Cancer Control Center (KCCC) from 2016 to the end of 2019. Data collected include diagnosis, patient demographics, performance status, number of previous lines of treatment, number of treatment cycles, side effects, best-tolerated dose, and treatment discontinuation due to intolerability. Univariate analysis with Pearson chi-square test were conducted to study co-relation between discontinuation rates and several factors. Results We had available data for 43 patients (23 males and 20 females). Of the patients, 83.7% had an ECOG performance status of 0 or 1. Seventy-three percent were diagnosed with metastatic CRC, 21% were diagnosed with HCC and 6% were diagnosed with GIST tumors. Half of the patients received 3 lines or more of treatment prior to regorafenib. The median number of cycles received was 3.7 with 11.6% of patients still on active treatment at the time of analysis. The most reported grade 3 and above side effects included rash (41.9%), fatigue (39.6 %), hypertension (25.6%), mucositis (21.9%), hand-foot syndrome (2.3%), and hyperbilirubinemia (4.6%). The best-tolerated dose was 80 mg and that was achieved in 44.2% of patients. The recommended dose of 160 mg could only be achieved in 20.9% of patients. The treatment was discontinued because of intolerability in 25.6% of patients. The discontinuation rates in those with ages 60 years and above versus below 60 years were 91% an d 68%, respectively. Conclusion In our cohort, the best-tolerated dose of regorafenib was 80 mg. Toxicity and intolerability of regorafenib lead to treatment discontinuation in nearly a quarter of patients. Patient age may influence tolerance and adherence to regorafenib. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Gastric Cancer Incidence and Mortality in French Guiana: South American or French?

xlomafota.13 shared this article with you from Inoreader Gastric Cancer Incidence and Mortality in French Guiana: South American or French? Via Latest Results for Journal of Gastrointestinal Cancer Abstract Purpose Gastric cancer is a frequent cancer in the tropics. The objective was to review a decade of gastric cancer data, and to study its spatial and temporal trends. Methods The cancer registry of French Guiana compiled exhaustive data on gastric cancer throughout French Guiana between 2005 and 2014. Age-standardized incidence and mortality rates were computed. Results With 187 new cases recorded, gastric cancer ranked 6th (4.3%). It was more frequent in men than in women. The median age at diagnosis was 62 years for men and 65 years for women. The incidence rate standardized to the world population over the period 2005–2014 was 14.3 cases of gastric cancer per 100,000 man-years and 7.3 per 100,000 woman-years. The death rate from gastric cancer, standardized to the world population over the period 2005–2014, was 8.6 deaths from gastric cancer per 100,000 man-years and 3.4 per 100,000 women-years. These measures were lower than what is reported in Latin America, similar to Martinique and Guadeloupe—two tropical French territories—and higher than in France. Conclusions Gastric cancer affected more males and the median age was younger than in France. Standardized incidence and mortality rates for gastric cancer in French Guiana were between those of France and those of Latin America, and they were comparable to those of the French West Indies. The downward trend in a context of rapid economic growth suggests further gains that could be achieved by improving electricity, water, and sanitation coverage throughout the territory despite challenging geography, and better access to care and Helicobacter pylori eradication. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Endoscopic Ultrasonography is a Promising Tool for Preoperative Prediction of the Operability of Pancreatic Carcinoma

xlomafota.13 shared this article with you from Inoreader Endoscopic Ultrasonography is a Promising Tool for Preoperative Prediction of the Operability of Pancreatic Carcinoma Via Latest Results for Journal of Gastrointestinal Cancer Abstract This work discussed the efficiency of endoscopic ultrasonography (EUS) as a diagnostic modality for early detection of pancreatic cancer. The present study was constructed by doing imaging modalities EUS on 24 patients admitted to surgery department in the faculty of medicine with suspected pancreatic malignancy. Pancreatic cancer was found more in older ages above 55 years predominately in males coming from rural areas presenting with abdominal pain with or without jaundice. Histopathological examination revealed that ductal adenocarcinoma represented by 70.83% of cases. This study also shows significant elevation in serum CA19-9 in the presenting cases to confirm a close relation between cancer pancreas and CA19-9 as a good biochemical marker for PC. EUS was found to be able to detect masses less than 20 mm in diameter. Moreover, EUS can accurately detect the mass nature. EUS showed correct information as regards lymph node involvement and vascular invasion whi ch affected the results of respectability of pancreatic masses. Finally, this study clearly showed that EUS is an accurate pre-operative tool in the assessment of nodal staging, vascular invasion, and respectability in patients with pancreatic adenocarcinoma. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Endoscopic Ultrasound-Guided Ethanol Injection Associated with Trans-arterial Embolization of a Giant Intra-abdominal Cavernous Hemangioma: Case Report and New Therapeutic Option

xlomafota.13 shared this article with you from Inoreader Endoscopic Ultrasound-Guided Ethanol Injection Associated with Trans-arterial Embolization of a Giant Intra-abdominal Cavernous Hemangioma: Case Report and New Therapeutic Option Via Latest Results for Journal of Gastrointestinal Cancer Abstract Background Cavernous hemangiomas are congenital hamartomatous lesions that originate from mesodermal tissue composed of dilated blood vessels. Abdominal pain and palpable mass are the most common presenting symptoms. The different types of treatment for symptomatic patients remain controversial. However, surgical resection is always the most preferred method when possible. To date, there are no reports of endoscopic ultrasound-guided (EUS-guided) absolute ethanol injection as a treatment for such disease when surgery is not an option. Case Presentation A 19-year-old girl with giant cavernous intra-abdominal hemangioma extending to the hepatic hilum, also affecting the gastric wall and occupying the entire supra-mesocolic cavity, initially presents with upper gastrointestinal bleeding and loss of 20 kg in 1 year (BMI = 18 kg/m2). Percutaneous angiography identified a mass with arterial blood supply by the left gastric artery that was embolized. After re-bleeding, an alternative treatment with EUS-guided injection of alcohol was proposed once resection was not feasible without major risks to a young patient. This procedure was repeated 15 and 45 days after the initial treatment, with the ethanol injection of 25 cc and 15 cc, respectively. On the second and third procedure dates, there was evident regression of the hemangioma. On the third procedure, it was possible to identify all anatomic structures that were not clear on the first EUS. After 45 days of last injection, abdominal CT and EUS showed no torious regression of the lesion. Eight months later, abdominal CT showed only a remnant lesion in the hepatogastric ligament with 129 cm3 on volumetry (87% lower in comparison to the initial image), and the patient remains asymptomatic with BMI of 26. In the most recent follow-up CT, 4 years and 2 months after first treatment, the patient presents with a slight increase in the hemangioma—now with 183 cm3 on volumetry. Conclusion Transgastric EUS-guided ethanol injection in the treatment of giant intra-abdominal cavernous hemangioma can provide good outcomes without major complications and can be repeated if necessary. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

TERRA Gene Expression in Gastric Cancer: Role of hTERT

xlomafota.13 shared this article with you from Inoreader TERRA Gene Expression in Gastric Cancer: Role of hTERT Via Latest Results for Journal of Gastrointestinal Cancer Abstract Purpose One of the most important serious malignancies is gastric cancer (GC) with a high mortality globally. In this way, beside the environmental factors, genetic parameter has a remarkable effective fluctuation in GC. Correspondingly, telomeres are nucleoprotein structures measuring the length of telomeres and they have special potential in diagnosis of various types of cancers. Defect protection of the telomeric length initiates the instability of the genome during cancer, including gastric cancer. The most common way of maintaining telomere length is the function of the telomerase enzyme that replicates the TTAGGG to the end of the 3′ chromosome. Methods In this review, we want to discuss the alterations of hTERT repression on the modification of TERRA gene expression in conjunction with the importance of telomere and telomerase in GC. Results The telomerase enzyme contains two essential components called telomerase reverse transcriptase (hTERT) and RNA telomerase (hTR, hTERC). Deregulation of hTERT plays a key role in the multistage process of tumorigenicity and anticancer drug resistance. The direct relationship between telomerase activity and hTERT has led to hTERT to be considered a key target for cancer treatment. Recent results show that telomeres are transcribed into telomeric repeat-containing RNA (TERRA) in mammalian cells and are long noncoding RNAs (lncRNAs) identified in different tissues. In addition, most chemotherapy methods have a lot of side effects on normal cells. Conclusion Telomere and telomerase are useful therapeutic goal. According to the main roles of hTERT in tumorigenesis, growth, migration, and cancer invasion, hTERT and regulatory mechanisms that control the expression of hTERT are attractive therapeutic targets for cancer treatment. Graphical abstract View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Immunohistochemical Expression Pattern of MLH1, MSH2, MSH6, and PMS2 in Tumor Specimen of Iranian Gastric Carcinoma Patients

xlomafota.13 shared this article with you from Inoreader Immunohistochemical Expression Pattern of MLH1, MSH2, MSH6, and PMS2 in Tumor Specimen of Iranian Gastric Carcinoma Patients Via Latest Results for Journal of Gastrointestinal Cancer Abstract Background Gastric cancer is the third leading cause of cancer-related death. Determining molecular and histopathologic tumor features, which may contribute to the development or progression of gastric cancer, can improve the prognosis. Expression patterns of DNA repair proteins such as MLH1, MSH2, MSH6, and PMS2 that are associated with microsatellite instability (MSI) are some of the markers that are useful in predicting the prognosis of gastric cancer. Purpose The purpose was to determine the immunohistochemical expression pattern of MLH1, MSH2, MSH6, and PMS2 in tumor specimens of Iranian gastric carcinoma patients. Methods In this prospective cohort, 186 consecutive patients with gastric cancer, attending Taleghani Hospital, were enrolled. The immunohistochemical expression patterns of MLH1, MSH2, MSH6, and PMS2 in tumor specimens among them were determined. Results The results of this study demonstrated that 91.4% of our gastric cancer patients were negative for MSI, and 8.6% of them were MSI positive. The positive MSI was seen in 5.9% and 15.7% of male and female subjects, respectively, with a significant difference (P = 0.043). The other variables were not related to MSI results (P > 0.05). Conclusion According to the obtained results, the expression of MLH1, MSH2, MSH6, and PMS2 in tumor specimens is positive in 8.6% of the total Iranian gastric cancer sample size, which is mainly positive in female subjects. However, it is not related to the location and stage of the tumor. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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Flumatinib versus Imatinib for Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia: A Phase III, Randomized, Open-label, Multi-center FESTnd Study

Cancer shared this article with you from Inoreader Flumatinib versus Imatinib for Newly Diagnosed Chronic Phase Chronic Myeloid Leukemia: A Phase III, Randomized, Open-label, Multi-center FESTnd Study Via Clinical Cancer Research recent ... Purpose: Flumatinib has been shown to be a more potent inhibitor of BCR-ABL1 tyrosine kinase than imatinib. We evaluated the efficacy and safety of flumatinib versus imatinib, for first-line treatment of chronic phase Philadelphia chromosome–positive chronic myeloid leukemia (CML-CP). Patients and Methods: In this study, 394 patients were randomized 1:1 to flumatinib 600 mg once daily (n = 196) or imatinib 400 mg once daily (n = 198) groups. Results: The rate of major molecular response (MMR) at 6 months (primary endpoint) was significantly higher with flumatinib than with imatinib (33.7% vs. 18.3%; P = 0.0006), as was the rate of MMR at 12 months (52.6% vs. 39.6%; P = 0.0102). At 3 months, the rate of early molecular response (EMR) was significantly higher in patients receiving flumatinib than in those receiving imatinib (82.1% vs. 53.3%; P < 0.0001). Compared with patients receiving imatinib, more patients receiving flumatinib achieved molecular remission 4 (MR4) at 6, 9, and 12 months (8.7% vs. 3.6%, P = 0.0358; 16.8% vs. 5.1%, P = 0.0002; and 23.0% vs. 11.7%, P = 0.0034, respectively). No patients had progression to accelerated phase or blast crisis in the flumatinib arm versus 4 patients in the imatinib arm by 12 months. Adverse events of edema, pain in extremities, rash, neutropenia, anemia, and hypophosphatemia were more frequent in imatinib arm, whereas diarrhea and alanine transaminase elevation were more frequent in flumatinib arm. Conclusions: Patients receiving flumatinib achieved significantly higher rates of responses, and faster and deeper responses compared with those receiving imatinib, indicating that flumatinib can be an effective first-line treatment for CML-CP. This trial was registered at www.clinicaltrials.gov as NCT02204644. See related commentary by Müller, p. 3 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

MRI and 18FET-PET Predict Survival Benefit from Bevacizumab Plus Radiotherapy in Patients with Isocitrate Dehydrogenase Wild-type Glioblastoma: Results from the Randomized ARTE Trial

Cancer shared this article with you from Inoreader MRI and 18FET-PET Predict Survival Benefit from Bevacizumab Plus Radiotherapy in Patients with Isocitrate Dehydrogenase Wild-type Glioblastoma: Results from the Randomized ARTE Trial Via Clinical Cancer Research recent ... Purpose: To explore a prognostic or predictive role of MRI and O-(2–18F-fluoroethyl)-L-tyrosine (18FET) PET parameters for outcome in the randomized multicenter trial ARTE that compared bevacizumab plus radiotherapy with radiotherpay alone in elderly patients with glioblastoma. Patients and Methods: Patients with isocitrate dehydrogenase wild-type glioblastoma ages 65 years or older were included in this post hoc analysis. Tumor volumetric and apparent diffusion coefficient (ADC) analyses of serial MRI scans from 67 patients and serial 18FET-PET tumor-to-brain intensity ratios (TBRs) from 31 patients were analyzed blinded for treatment arm and outcome. Multivariate Cox regression analysis was done to account for established prognostic factors and treatment arm. Results: Overall survival benefit from bevacizumab plus radiotherapy compared with radiotherapy alone was observed for larger pretreatment MRI contrast-enhancing tumor [HR per cm3 0.94; 95% confidence interval (CI), 0.89–0.99] and for higher ADC (HR 0.18; CI, 0.05–0.66). Higher 18FET-TBR on pretreatment PET scans was associated with inferior overall survival in both arms. Response assessed by standard MRI-based Response Assessment in Neuro-Oncology criteria was associated with overall survival in the bevacizumab plus radiotherapy arm by trend only (P = 0.09). High 18FET-TBR of noncontrast-enhancing tumor portions during bevacizumab therapy was associated with inferior overall survival on multivariate analysis (HR 5.97; CI, 1.16–30.8). Conclusions: Large pretreatment contrast-enhancing tumor mass and higher ADCs identify patients who may experience a survival benefit from bevacizumab plus radiotherapy. Persistent 18FET-PET signal of no longer contrast-enhancing tumor after concomitant bevacizumab plus radiotherapy suggests pseudoresponse and predicts poor outcome. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Phase I Study of Alvocidib Followed by 7+3 (Cytarabine + Daunorubicin) in Newly Diagnosed Acute Myeloid Leukemia

Cancer shared this article with you from Inoreader Phase I Study of Alvocidib Followed by 7+3 (Cytarabine + Daunorubicin) in Newly Diagnosed Acute Myeloid Leukemia Via Clinical Cancer Research recent ... Purpose: Alvocidib is a cyclin-dependent kinase 9 inhibitor leading to downregulation of the antiapoptotic BCL-2 family member, MCL-1. Alvocidib has shown clinical activity in a timed sequential regimen with cytarabine and mitoxantrone in relapsed/refractory and newly diagnosed acute myeloid leukemia (AML) but has not been studied in combination with traditional 7+3 induction therapy. Patients and Methods: A multiinstitutional phase I dose-escalation study of alvocidib on days 1–3 followed by 7+3 (cytarabine 100 mg/m2/day i.v. infusion days 5–12 and daunorubicin 60 mg/m2 i.v. days 5–7) was performed in newly diagnosed AML ≤65 years. Core-binding factor AML was excluded. Results: There was no MTD on this study; the recommended phase II dose of alvocidib was 30 mg/m2 i.v. over 30 minutes followed by 60 mg/m2 i.v. infusion over 4 hours. There was one dose-limiting toxicity of cytokine release syndrome. The most common grade ≥3 nonhematologic toxicities were diarrhea (44%) and tumor lysis syndrome (34%). Overall, 69% (22/32) of patients achieved complete remission (CR). In an exploratory cohort, eight of nine (89%) patients in complete remission had no measurable residual disease, as determined by a centralized flow cytometric assay. Clinical activity was seen in patients with secondary AML, AML with myelodysplastic syndrome–related changes, and a genomic signature of secondary AML (50%, 50%, and 92% CR rates, respectively). Conclusions: Alvocidib can be safely administered prior to 7+3 induction with encouraging clinical activity. These findings warrant further investigation of alvocidib combinations in newly diagnosed AML. This study was registered at clinicaltrials.gov identifier NCT03298984. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.