The Role of Neuropilin-2 in the Epithelial to Mesenchymal Transition of Colorectal Cancer: A Systematic Review

Neuropilin-2 (NRP-2) expression has been found in various investigations on the expression and function of NRP-2 in colorectal cancer. The link between NRP-2 and colorectal cancer, as well as the mechanism that regulates it, is still mostly unclear. This systematic review was carried out according to the Cochrane guidelines for systematic reviews. We searched PubMed, Embase®, MEDLINE, Allied & Complementary MedicineTM, Medical Toxicology & Environmental Health, DH-DATA: Health Administration for articles published before 1 October 2021. The following search terms were used: “neuropilin-2” “neuropilin 2”, “NRP2” and “NRP-2”, “colorectal cancer”, “colon cancer”. Ten articles researching either tumor tissue samples, cell lines, or mice models were included in this review. The majority of human primary and metastatic colon cancer cell lines expressed NRP-2 compared to the normal colonic mucosa. NRPs have been discovered in human cancers as well as neovasculature. The presence of NRP-2 appears to be connected to the epithelial–mesenchymal transition’s function in cancer dissemination and metastatic evolution. The studies were heterogeneous, but the data assessed indicates NRP-2 might have an impact on the metastatic potential of colorectal cancer cells. Nevertheless, further research is needed

Immunotherapy-Related Publications in Colorectal Cancer: A Bibliometric Analysis

Patients with microsatellite-instability-high (MSI-H) or mismatched repair-deficient colorectal cancer (CRC) appear to be responsive to checkpoint inhibitors. This study aimed to assess research trends in CRC immunotherapy. Publication patterns of articles covering immunotherapies in CRC in the Web of Science Core Collection database were retrospectively examined using VOS viewer software (version 1.6.16) prior to 25 May 2021. Ultimately, 3977 records were identified that were published between 1975 and 2021, which received a total of 128,681 citations (an average of 32.36 citations per item), with a noticeable rise in 2014. The majority of articles were published in the US (35.8%), China (17.7%), and Germany (9.4%). Publications mainly originated from the Institut National de la Santé Et De La Recherche Medicale Inserm, followed by the University of Texas System and Harvard University; however, Johns Hopkins University received the most citations (18,666 for 69 publications). The Journal of Clinical Oncology issued the most publications (n = 146), while the most referenced item (7724 citations) was published in the New England Journal of Medicine in 2012. The most common keywords were associated with tumors (expression and microsatellite instability) or immune system components (t-cells/dendritic cells). The findings demonstrate the scientific community’s interest in the MSI-H subtype of colorectal tumors and how immunotherapy may be employed more successfully to treat metastatic CRC

Electrical and Electro-Thermal Characteristics of (Carbon Black-Graphite)/LLDPE Composites with PTC Effect

Electrical properties and electro-thermal behavior were studied in composites with carbon black (CB) or hybrid filler (CB and graphite) and a matrix of linear low-density polyethylene (LLDPE). LLDPE, a (co)polymer with low crystallinity but with high structural regularity, was less studied for Positive Temperature Coefficient (PTC) applications, but it would be of interest due to its higher flexibility as compared to HDPE. Structural characterization by scanning electron microscopy (SEM) confirmed a segregated structure resulted from preparation by solid state powder mixing followed by hot molding. Direct current (DC) conductivity measurements resulted in a percolation threshold of around 8% (w) for CB/LLDPE composites. Increased filler concentrations resulted in increased alternating current (AC) conductivity, electrical permittivity and loss factor. Resistivity-temperature curves indicate the dependence of the temperature at which the maximum of resistivity is reached (Tmax(R)) on the filler concentration, as well as a differentiation in the Tmax(R) from the crystalline transition temperatures determined by DSC. These results suggest that crystallinity is not the only determining factor of the PTC mechanism in this case. This behavior is different from similar high-crystallinity composites, and suggests a specific interaction between the conductive filler and the polymeric matrix. A strong dependence of the PTC effect on filler concentration and an optimal concentration range between 14 and 19% were also found. Graphite has a beneficial effect not only on conductivity, but also on PTC behavior. Temperature vs. time experiments, revealed good temperature self-regulation properties and current and voltage limitation, and irrespective of the applied voltage and composite type, the equilibrium superficial temperature did not exceed 80 °C, while the equilibrium current traversing the sample dropped from 22 mA at 35 V to 5 mA at 150 V, proving the limitation capacities of these materials. The concentration effects revealed in this work could open new perspectives for the compositional control of both the self-limiting and interrupting properties for various low-temperature applications

How Much Burnout and Coping Influence Quality of Life among Young Oncology Providers in Romania during the COVID-19 Pandemic

This study aims to investigate the correlations between burnout, coping strategies, and quality of life among young oncology healthcare workers in Romania during the COVID-19 pandemic. We collected the data using an online questionnaire consisting of sociodemographic questions, the Maslach Burnout Inventory, the COPE questionnaire, and the 15D instrument. A total of 122 healthcare providers responded to our survey. We evaluated the differences in the scores among the three groups of healthcare workers in oncology under 40 years old: medical oncologists (n = 87), radiation oncologists (n = 11), and oncology nurses (n = 24). Finally, we conducted a correlation analysis between the dimensions of burnout, coping, and quality of life. Overall, the medical oncologists exhibited much higher burnout levels than nurses in the COVID-19 pandemic outbreak, having statistically significant higher levels of emotional exhaustion, depersonalization, and lack of personal achievement. Some factors were inversely associated with burnout: active approach, planning, positive interpretation and growth, and acceptance. Our findings illustrated a very good level of health-related quality of life (average = 0.93, SD = 0.06), and no statistically significant differences were found in the quality of life between the three groups. This study was the first to identify the profile of young oncology providers in Romania. Our findings may be relevant in creating preventive strategies for burnout and increasing the quality of life in Romanian young oncology providers in future crises

Bevacizumab Treatment for Metastatic Colorectal Cancer in Real-World Clinical Practice

Background and Objectives: Colorectal cancer (CRC) is a leading cause of cancer-related mortality and morbidity worldwide. Bevacizumab was approved for the treatment of metastatic colorectal cancer (mCRC) based on favorable benefit-risk assessments from randomized controlled trials, but evidence on its use in the real-world setting is limited. The aim of the current study is to evaluate the outcomes and safety profile of bevacizumab in mCRC in a real-world setting in Romania. Patients and Methods: This was an observational, retrospective, multicentric, cohort study conducted in Romania that included patients with mCRC treated with bevacizumab as part of routine clinical practice. Study endpoints were progression-free survival, overall survival, adverse events, and patterns of bevacizumab use. Results: A total of 554 patients were included in the study between January 2008 and December 2018. A total of 392 patients (71%) received bevacizumab in the first line and 162 patients (29%) in the second line. Bevacizumab was mostly combined with a capecitabine/oxaliplatin chemotherapy regimen (31.6%). The median PFS for patients treated with bevacizumab was 8.4 months (interquartile range [IQR], 4.7–15.1 months) in the first line and 6.6 months (IQR, 3.8–12.3 months) in the second line. The median OS was 17.7 months (IQR, 9.3–30.6 months) in the first line and 13.5 months (IQR, 6.7–25.2 months) in the second line. Primary tumor resection was associated with a longer PFS and OS. The safety profile of bevacizumab combined with chemotherapy was similar to other observational studies in mCRC. Conclusions: The safety profile of bevacizumab was generally as expected. Although the PFS was generally similar to that reported in other studies, the OS was shorter, probably due to the less frequent use of bevacizumab after disease progression and the baseline patient characteristics. Patients with mCRC treated with bevacizumab who underwent resection of the primary tumor had a higher OS compared to patients with an unresected primary tumor

Clinical, Pathological and Molecular Insights on KRAS, NRAS, BRAF, PIK3CA and TP53 Mutations in Metastatic Colorectal Cancer Patients from Northeastern Romania

Mutations in RAS, BRAF, PIK3CA, and TP53 are well-established genetic abnormalities in metastatic colorectal cancer (mCRC). However, limited information is available for patients from Eastern Europe, including Romania. In this retrospective analysis, we investigated 104 mCRC patients from the Northeastern region of Romania to determine the frequency, distribution, coexistence, and clinicopathological and molecular correlations of these mutations. TP53 was the most frequently mutated gene (73.1%), followed by KRAS (45.2%) and PIK3CA (6.7%). Patients with KRAS mutant tumors and wild-type TP53 genotype were found to have no personal history of gastrointestinal cancer (p = 0.02, p = 0.007). KRAS mutations in exon 3 were associated with the female gender (p = 0.02) and the absence of lymph node invasion (p = 0.02). PIK3CA mutations were linked to the absence of lymph node invasion (p = 0.006). TP53 mutations were associated with KRAS mutations in exon 2 (p = 0.006), ulcerated histopathologic type (p = 0.04), and G2 differentiation (p = 0.01). It provides novel insights into genetic variations specific to the population from Northeastern Romania, which has been underrepresented in previous studies within Eastern Europe. Furthermore, our findings enable the development of genetic profiles in a developing country with limited access to specialized genetic tests and facilitate comparisons with other populations

Safety and tolerability of subcutaneous trastuzumab for the adjuvant treatment of human epidermal growth factor receptor 2-positive early breast cancer: SafeHer phase III study's primary analysis of 2573 patients

Aim To assess the safety and tolerability of adjuvant subcutaneous trastuzumab (Herceptin® SC, H SC), delivered from an H SC Vial via hand-held syringe (Cohort A) or single-use injection device (Cohort B), with or without chemotherapy, for human epidermal growth factor receptor 2 (HER2)-positive stage I to IIIC early breast cancer (EBC) in the phase III SafeHer study (NCT01566721). Methods Patients received 600 mg fixed-dose H SC every 3 weeks for 18 cycles. The chemotherapy partner was at the investigators' discretion (H SC monotherapy was limited to ≤10% of the population). Data from the first H SC dose until 28 days (plus a 5-day window) after the last dose are presented. Results are descriptive. Results In the overall population, 2282/2573 patients (88.7%) experienced adverse events (AEs). Of the above, 128 (5.0%) patients experienced AEs leading to study drug discontinuation; 596 (23.2%) experienced grade ≥ 3 AEs and 326 (12.7%) experienced serious AEs. Grade ≥ 3 cardiac disorders were reported in 24 patients (0.9%), including congestive heart failure in eight (0.3%). As expected, the AE rates varied according to the timing of chemotherapy in both cohorts, with higher rates in concurrent versus sequential chemotherapy subgroups. In the concurrent chemotherapy subgroup, AEs were more common during the actual period of concurrent chemotherapy compared with the period when patients did not receive concurrent chemotherapy. Conclusion SafeHer confirms the safety and tolerability of the H SC 600 mg fixed dose for 1 year (every 3 weeks for 18 cycles) as adjuvant therapy with concurrent or sequential chemotherapy for HER2-positive EBC. These primary analysis results are consistent with the known safety profile for intravenous H and H SC