RESUMO
BACKGROUND: Recent investigations have reported the benefits of using a tyrosine kinase inhibitor, dasatinib (DA), as well as programmed death-ligand 1 (PD-L1) inhibitors in the management of several solid tumors, including breast cancer. Nevertheless, the outcome of the combination of these inhibitors on HER2-positive breast cancer is not explored yet. METHODS: Herein, we investigated the impact of DA and PD-L1 inhibitor (BMS-202) combination on HER2-positive breast cancer cell lines, SKBR3 and ZR75. RESULTS: Our data reveal that the combination significantly inhibits cell viability of both cancer cell lines as compared to monotreatment. Moreover, the combination inhibits epithelial-mesenchymal transition (EMT) progression and reduces cancer cell invasion by restoring E-cadherin and ß-catenin expressions and loss of vimentin, major biomarkers of EMT. Additionally, the combination reduces the colony formation of both cell lines in comparison with their matched control. Also, the combination considerably inhibits the angiogenesis of the chorioallantoic membrane model compared with monotreatment. Molecular pathway analysis of treated cells shows that this combination blocks HER2, AKT, ß-catenin, and JNK1/2/3 activities. CONCLUSION: Our findings implicate that a combination of DA and BMS-202 could have a significant impact on the management of HER2-positive breast cancer.
RESUMO
Epstein-Barr virus (EBV) belongs to the group of gamma-herpes viruses and was the first recognized human oncovirus. EBV is responsible for infectious mononucleosis and multiple lymphoid and epithelial malignancies including B-cell lymphomas (Burkitt lymphoma, Hodgkin lymphoma, and post-transplant lymphoproliferative disorder), various T-cell/NK lymphoproliferative disorders, nasopharyngeal carcinoma, and gastric carcinoma, respectively. In addition, the presence of EBV has been documented in other cancers including breast, prostate, oral, and salivary gland carcinomas. The presence and role of EBV in cervical cancer and its precursor lesions (CIN) have also been described, but the results from the literature are inconsistent, and the causal role of EBV in cervical cancer pathogenesis has not been established yet. In the present review, we briefly surveyed and critically appraised the current literature on EBV in cervical cancer and its variants (lymphoepithelioma-like carcinoma) as well as its precursor lesions (CIN). In addition, we discussed the possible interactions between EBV and human papilloma virus as well as between EBV and immune checkpoint regulators (PD-L1). Though further studies are needed, the available data suggest a possible causal relationship between EBV and cervical cancer pathogenesis.
RESUMO
Gliomas are the most common malignant brain tumors and account for around 60% of all primary central nervous system cancers. Glioblastoma multiforme (GBM) is a grade IV glioma associated with a poor outcome despite recent advances in chemotherapy. The etiology of gliomas is unknown, but neurotropic viruses including the Epstein-Barr virus (EBV) that is transmitted via salivary and genital fluids have been implicated recently. EBV is a member of the gamma herpes simplex family of DNA viruses that is known to cause infectious mononucleosis (glandular fever) and is strongly linked with the oncogenesis of several cancers, including B-cell lymphomas, nasopharyngeal, and gastric carcinomas. The fact that EBV is thought to be the causative agent for primary central nervous system (CNS) lymphomas in immune-deficient patients has led to its investigations in other brain tumors including gliomas. Here, we provide a review of the clinical literature pertaining to EBV in gliomas and discuss the possibilities of this virus being simply associative, causative, or even an experimental artifact. We searched the PubMed/MEDLINE databases using the following key words such as: glioma(s), glioblastoma multiforme, brain tumors/cancers, EBV, and neurotropic viruses. Our literature analysis indicates conflicting results on the presence and role of EBV in gliomas. Further comprehensive studies are needed to fully implicate EBV in gliomagenesis and oncomodulation. Understanding the role of EBV and other oncoviruses in the etiology of gliomas, would likely open up new avenues for the treatment and management of these, often fatal, CNS tumors.
RESUMO
AIM: To determine the incidence and clinico-pathological profile of appendiceal carcinoids in a cohort of patients undergoing emergency appendicectomies for clinically suspected acute appendicitis in Sharjah, United Arab Emirates (UAE). METHODS: The study included the retrospective data of 964 patients operated for clinically suspected acute appendicitis, and the resected specimens were received at Al-Qasmi Hospital (Sharjah) from January 2010 to December 2010. The data of the patients who were histologically reported to have carcinoid tumors of the appendix were extensively evaluated for the patient's demographics, indication for surgery, surgical procedure, tumor localization in the appendix, diameter of the lesion, concomitant appendicitis, immunohistochemistry studies and clinical follow-up. RESULTS: Out of the 964 patients included in the study, 9 (0.93%) were found to have appendiceal carcinoids. The mean age reported was 28.7 years with a male to female ratio of 2:1. Eight tumors were located near the tip of the appendix with a mean diameter of 3.3 mm, while the remaining one was near the proximal end of the appendix. All the cases were associated with concomitant suppurative appendicitis. In seven reported cases, tumors were confined to the muscular layer while in one case each there was an extension to the serosa and mesoappendix, respectively. All tumors were found to be positive for chromogranin A, synaptophysin and neuron-specific enolase on immunohistochemistry but negative for cytokeratin-7. None of the patients developed recurrence or any reportable complications in the short follow-up period (12-26 mo) that was arranged as a six-monthly re-evaluation by abdominal ultrasonography. CONCLUSION: Our study found a higher incidence of appendiceal carcinoids in patients undergoing emergency appendectomy for acute appendicitis in Sharjah, UAE compared to two previous studies from the Persian Gulf region. Interestingly, tumors were found to be more commonly in young males, which is in contrast to previous studies. Moreover, all the tumors were positive for common neuroendocrine markers.
