Predatory or pseudo journals have recently come into focus due to their massive internet expansion and extensive spam email soliciting. Recent studies explored this urging problem in several biomedical disciplines. In the present study, we identified 69 potential predatory (pseudo) pathology journals that were contrasted to 89 legitimate pathology journals obtained from the major bibliographic databases. All potential predatory journals in pathology shared at least one of the features proposed by previous studies (e.g. a poor web-site integrity, submissions via email, unclear or ambiguous peer-review process, missing names of the editorial board members, missing or pending the journal ISSN). Twenty-one (30%) of the potential predatory pathology journals had misleading titles mimicking those of legitimate journals. Only one of the identified journals was listed in the Directory of Open Access journals whereas none (0%) was indexed in PubMed/MEDLINE or Web of Science, listed in the Committee on Publication Ethics nor have they had a legitimate impact factor in the Journal Citation Reports.

ABSTRACT Epstein-Barr virus (EBV) is a well-characterized oncovirus, associated with several malignancies. The complex and heterogeneous nature of colorectal cancer (CRC) has led to many epidemiological causal associations with CRC. However, a direct causal link between microbial infections and CRC has not been established yet. Our review indicates that the current evidence for the presence and role in EBV in CRC is insufficient and contradictory. The design of the analyzed studies, sample size as well as methodology used for EBV detection varied markedly and consequently may not lead to meaningful conclusions. The presence of EBV in other colorectal tumors (lymphomas, smooth muscle tumors) is in line with their status at other anatomic locations and may have therapeutic implications with EBV-specific vaccines. On the other hand, studies exploring EBV in colorectal adenoma-carcinoma sequence and its molecular genetic characteristics are largely missing and may significantly contribute to a better understanding of the role of EBV in CRC.

With the increasing popularity of water-pipe smoking (WPS), it is critical to comprehend how WPS may affect women’s health. The main goal of this study is to identify the potential outcome of WPS on human breast cancer progression. Two breast cancer cell lines, MCF7 and BT20, were used in this investigation. We explored the outcome of WPS on cell morphology and cell invasion using inverted microscope and Biocoat Matrigel invasion chambers. On the other hand, Western blot was employed to study the expression patterns of key control genes of cell adhesion and invasion. Our data reveal that WPS induces epithelial–mesenchymal transition (EMT) of MCF7 and BT20 breast cancer cell lines; thus, WPS enhances cell invasion ability of both cell lines in comparison with their matched controls. More significantly, WPS provokes a down- and up-regulation of E-cadherin and focal adhesion kinase (FAK), respectively, which are important key regulators of cancer progression genes. Finally, our data point out that WPS incites the activation of Erk1/Erk2, which could be behind the stimulation of EMT and invasion as well as the deregulation of E-cadherin and FAK expression. Our data show, for the first time, that WPS initiates EMT and stimulates cell invasion of breast cancer cells, which could incite metastatic development in breast cancer patients. Thus, we believe that further studies, both in vitro and in vivo, are required to elucidate the pathogenic outcome of WPS on cancer progression of several human carcinomas including breast.

School of Medicine, University of Sarajevo, Sarajevo, Bosnia and Herzegovina Department of Pathology, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina Department of Radiology, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina Department of Oncology, Clinical Center, University of Sarajevo, Sarajevo, Bosnia and Herzegovina College of Medicine, Qatar University, Doha, Qatar

Epstein–Barr virus (EBV) has been recently shown to be co-present with high-risk human papillomaviruses (HPVs) in human cervical cancer; thus, these oncoviruses play an important role in the initiation and/or progression of this cancer. Accordingly, our group has recently viewed the presence and genotyping distribution of high-risk HPVs in cervical cancer in Syrian women; our data pointed out that HPVs are present in 42/44 samples (95%). Herein, we aim to explore the co-prevalence of EBV and high-risk HPVs in 44 cervical cancer tissues from Syrian women using polymerase chain reaction, immunohistochemistry, and tissue microarray analyses. We found that EBV and high-risk HPVs are co-present in 15/44 (34%) of the samples. However, none of the samples was exclusively EBV-positive. Additionally, we report that the co-expression of LMP1 and E6 genes of EBV and high-risk HPVs, respectively, is associated with poorly differentiated squamous cell carcinomas phenotype; this is accompanied by a strong and diffuse overexpression of Id-1 (93% positivity), which is an important regulator of cell invasion and metastasis. These data imply that EBV and HPVs are co-present in cervical cancer samples in the Middle East area including Syria and their co-presence is associated with a more aggressive cancer phenotype. Future investigations are needed to elucidate the exact role of EBV and HPVs cooperation in cervical carcinogenesis.

Multiple myeloma (MM), the second most common hematologic malignancy, is characterized by the clonal expansion of plasma cells. Despite dramatic improvements in patients′ survival over the past decade due to advances in therapy exploiting novel molecular targets (immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies), the treatment of relapsed and refractory disease remains challenging. Recent studies confirmed complex, dynamic, and heterogeneous genomic alterations without unifying gene mutations in MM patients. In the current review, we survey recent therapeutic strategies, as well as molecular profiling data on MM, with emphasis on relapsed and refractory cases. A critical appraisal of novel findings and of their potential therapeutic implications will be discussed in detail, along with the author’s own experiences/views.

Discoidin domain receptors DDR1 and DDR2 are the only receptor tyrosine kinases that bind to and signal in response to collagen. In cancer, DDRs have been shown to play a key role in mediating the crosstalk between tumor cells and the stromal collagen matrix. Because prostate cancer (PCa) preferentially metastasizes to bone, a collagen-rich microenvironment, we set out to investigate the role of DDR1 in intraosseous growth of PC3 cells, a human PCa cell line that expresses DDR1 but not DDR2. PC3 cells were engineered to express short hairpin RNAs (shRNAs) against DDR1, or a scrambled shRNA as a control. These cells were inoculated into the tibiae of male SCID mice, and then bone response and intraosseous tumor growth evaluated by X-ray and histomorphometry. Whereas no differences were observed in bone response (osteolytic lesions), downregulation of DDR1 in PC3 cells was associated with a significant increase in intraosseous tumor growth when compared to control PC3 cells (P Citation Format: R. Daniel Bonfil, Anjum Sohail, Semir Vranic, Daniel S. Oliveira, Dongping Shi, Wei Chen, Hyejeong Jang, Allen D. Saliganan, Benjamin D. Wasinski, Hyeong-Reh C. Kim, Rafael A. Fridman. Discoidin domain receptor 1 (DDR1): A potential suppressor of prostate cancer progression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1070.

BACKGROUND Cancer of unknown primary (CUP) accounts for approximately 3% of all malignancies. Avoiding immune destruction is a major cancer characteristic and therapies aimed at immune checkpoint blockade are in use for several specific cancer types. A comprehensive survey of predictive biomarkers to immune checkpoint blockade in CUP were explored in this study. METHODS About 389 cases of CUP were analysed for mutations in 592 genes and 52 gene fusions using a massively parallel DNA sequencing platform (next-generation sequencing [NGS]). Total mutational load (TML) and microsatellite instability (MSI) were calculated from NGS data. PD-L1 expression was explored using immunohistochemistry (with 5% cutoff value). RESULTS High TML was seen in 11.8% (46/389) of tumours. MSI-high (MSI-H) was detected in 7/384 (1.8%) of tumours. Tumour PD-L1 expression was detected in 80/362 CUP (22%). A small proportion of CUP cases harboured genetic alterations of negative predictive biomarkers to immune checkpoint inhibitors (predictors to hyperprogression) including MDM2 gene amplification (2%) and loss of function JAK2 gene mutations (1%). Amplifications of CD274 (PD-L1) and PDCD1LG2 (PD-L2) genes were also rare (1.4% and 0.8%, respectively). The most frequently mutated genes were TP53 (54%), KRAS (22%), ARID1A (13%), PIK3CA (9%), CDKN2A (8%), SMARCA4 (7%) and PBRM1, STK11, APC, RB1 (5%, respectively). CONCLUSIONS Using a multiplex testing approach, 28% of CUP carried one or more predictive biomarkers (MSI-H, PD-L1 and/or TML-H) to the immune checkpoint blockade, providing a novel option for treatment in patients with CUP.

Oncoviruses are implicated in around 20% of all human cancers including both solid and non-solid malignancies. Epstein–Barr virus (EBV) and human papillomaviruses (HPVs) are the most common oncoviruses worldwide. Currently, it is well established that onco-proteins of EBV (LMP1, LMP2A, and EBNA1) and high-risk HPVs (E5 and E6/E7) play an important role in the initiation and/or progression of several human carcinomas, including cervical, oral, and breast. More significantly, it has been recently pointed out that viral onco-proteins of EBV and high-risk HPVs can be co-present and consequently cooperate to initiate and/or amplify epithelial–mesenchymal transition (EMT), which is the hallmark of cancer progression and metastasis. This could occur by β-catenin, JAK/STAT/SRC, PI3k/Akt/mTOR, and/or RAS/MEK/ERK signaling pathways, which onco-proteins of EBV and HPVs share. This review presents the most recent advances related to EBV and high-risk HPVs onco-proteins interactions and their roles in the progression of human carcinomas especially oral and breast via the initiation of EMT.

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.

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.