CD47, also known as integrin-associated protein, is a constitutively and ubiquitously expressed transmembrane receptor. CD47 is conserved across amniotes including mammals, reptiles, and birds. Expression is increased in many cancers and, in non-malignant cells, by stress and with aging. The up-regulation of CD47 expression is generally epigenetic, whereas gene amplification occurs with low frequency in some cancers. CD47 is a high affinity signaling receptor for the secreted protein thrombospondin-1 (THBS1) and the counter-receptor for signal regulatory protein-α (SIRPA, SIRPα) and SIRPγ (SIRPG). CD47 interaction with SIRPα serves as a marker of self to innate immune cells and thereby protects cancer cells from phagocytic clearance. Consequently, higher CD47 correlates with a poor prognosis in some cancers, and therapeutic blockade can suppress tumor growth by enhancing innate antitumor immunity. CD47 expressed on cytotoxic T cells, dendritic cells, and NK cells mediates inhibitory THBS1 signaling that further limits antitumor immunity. CD47 laterally associates with several integrins and thereby regulates cell adhesion and migration. CD47 has additional lateral binding partners in specific cell types, and ligation of CD47 in some cases modulates their function. THBS1-CD47 signaling in non-malignant cells inhibits nitric oxide/cGMP, calcium, and VEGF signaling, mitochondrial homeostasis, stem cell maintenance, protective autophagy, and DNA damage response, and promotes NADPH oxidase activity. CD47 signaling is a physiological regulator of platelet activation, angiogenesis and blood flow. THBS1/CD47 signaling is frequently dysregulated in chronic diseases.
Tumours derived from Langerhans cells (LCs) are divided into two main subgroups, according to the degree of cytological atypia and clinical aggressiveness: LC histiocytosis (LCH) and LC sarcoma. Both subgroups maintain the phenotypic profile and ultrastructural features of LCs. LCH is a clonal neoplastic proliferation of Langerhans-type cells that express CD1a, langerin, and S100 protein, showing Birbeck granules by ultrastructural examination. Here the clinicopathological of LCH will be discussed.
Review on t(12;15)(p13;q25), with data on clinics, and the genes involved.
PARP1 (poly(ADP-ribose) polymerase 1) is a nuclear protein involved in the regulation of various biological processes including apoptosis, DNA repair for the maintenance of genome integrity, epigenetic marking of chromatin, assembly of higher-order chromatin structures, transcriptional activation, differentiation, proliferation, and cell cycle. Particularly, due to its decisive role in several DNA repair pathways, the inhibition of PARP1 has emerged as a prominent therapeutic option in cancer treatment, by improving the efficiency of chemotherapeutics or radiation therapy.
ERBB family member epidermal receptor tyrosine kinase (EGFR) is composed of 28 exons and 27 introns. EGFR codes for 11 transcripts and 8 of them are protein coding. EGFR is a transmembrane glycoprotein that can be activated by several different ligands such as epidermal growth factor (EGF), transforming growth factor-alpha (TGFA), heparin-binding EGF-like growth factor (HBEGF), betacellulin (BTC), amphiregulin (AREG), epiregulin (EREG), and epigen (EPGN) (Singh, 2016). Ligand binding induces the dimerization of EGFR and autophosphorylation followed by a cascade of downstream phosphorylation events (Capuani et al., 2015). EGFR activation plays a key role in cell survival, proliferation, migration and differentiation (Purba, 2017).
Case report on B-cell acute lymphoblastic leukemia with t(2;9)(p11;p13) involving the immunoglobulin kappa locus (IGK) and PAX-5.
APC-associated polyposis conditions result from a constitutional heterozygous pathogenic variant in the APC gene. These conditions include three main clinical phenotypes: the familial adenomatous polyposis (FAP), the attenuated FAP (AFAP) and the gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS). This phenotypic variability corresponds to the differences in the location of the pathogenic variant within the APC gene, even though variations among the individuals and within the families with the identical APC pathogenic variant may occur. Colorectal screening should begin from age 10 to 12 years in FAP and in late teens in AFAP, or earlier if there are gastrointestinal symptoms; the timing of surgery and the extent of resection should be determined on the basis of patient's personal history. Esophagogastroduodenoscopy is recommended by age 20-30 years or prior to colon surgery. Data to support screening for other cancers and manifestations associated with FAP are limited. The efficacy of the screening for gastric cancer and of prophylactic gastrectomy for patients with GAPPS is currently unknown.
Review on congenital/neonatal and infant leukemias, with data on clinics, pathology, and involved genes.
Review of histologic subtypes of mesothelioma, with associated clinical, pathologic, and molecular data.
BIRC7, also known as livin, is a member of the Inhibitor of Apoptosis Protein (IAP) family and is linked to the prevention of cell death induced by apoptosis, by directly or indirectly preventing caspase activity. In general, as most IAPs, BIRC7 expression is not detectable in normal differentiated adult tissues, with the exception of placenta, spleen, lymph nodes and developing embryonic tissues. On the other hand, BIRC7 overexpression has been reported in a variety of tumor types, in which it is associated to malignancy and chemoresistance. Currently, there are some unanswered questions about BIRC7, including its interaction with caspases, a potential paradoxical role in the apoptotic process, and specific functions/affinities of the BIRC7α and BIRC7β splice variants. Moreover, several studies have demonstrated the value of BIRC7 as a therapeutic target in a number of cancer types. This review mainly focuses on the role of BIRC7 in cancer cell biology and its clinical significance, demonstrating aspects of its DNA/RNA and protein, as well as its relevance in cancer diagnosis and prognosis.
Review on Primary Cutaneous CD8 Aggressive Epidermotropic Cytotoxic T Cell Lymphoma, with data on clinics, and the genes involved.
CDC7 is a serine-threonine kinase that participates in multiple cellular processes, including DNA replication, chromosomal segregation, S phase cell cycle progression, and DNA damage checkpoint. CDC7 is frequently highly expressed in several types of neoplasm, and it has been associated with cancer development and poor clinical outcomes. In different cancer models, functional studies indicated that CDC7 may be an attractive target for antineoplastic therapy, and CDC7 inhibitors have been developed. The present review on CDC7 contains data on DNA/RNA, the protein encoded, and the implication of this gene in cancer cell biology and clinical outcomes.
