Cancer Stem Cell Markers in Esophageal Cancer

Esophageal carcinoma is one of the most malignant of all tumors, and affected patients have low survival rates. The lack of good prognostic and therapeutic targets indicate the mysterious biology of this cancer. Recently, studies with cancer stem cells (CSCs) revealed some clues for better understanding of cancer biology and development. CSCs are derived from normal stem cells and have essential roles in tumor initiation and development of malignancies, such as esophageal carcinoma. Self-renewal studies in CSCs have improved our understanding of the factors that regulate CSCs behaviour and may result in improved prognostic markers and new therapeutic targets. Abnormal activity of major cell signaling pathways such as Shh, Notch, and Wnt play important roles in converting stem cells from normal to cancerous. This manuscript reviews the importance of several processes in the maintenance of esophageal CSCs and introduces probable useful markers for CSC based ESCC therapy

Role of SIZN1 in Esophageal Squamous Cell Carcinoma

Background: Bone morphogenetic proteins are a family of cytokines and growth factors that are involved in tumorigenesis. ZCCHC12 (SIZN1), as a transcriptional coactivator of bone morphogenetic protein signaling, is identified as a positive regulator of central nervous system development during embryogenesis. It positively regulates the CREB and AP1 transcription factors that cooperate with the bone morphogenetic protein signaling pathway. In the present study, SIZN1 mRNA expression was assessed in esophageal squamous cell carcinoma patients. Methods: The levels of SIZN1 mRNA expression in tumor tissues from 50 patients with esophageal squamous cell carcinoma were compared with their corresponding normal margins by using real-time polymerase chain reaction. Results: We observed that 10 out of 50 (20%) cases overexpressed SIZN1, whereas 40 out of 50 (80%) cases showed either normal or under expression of SIZN1. There was a significant correlation between the levels of SIZN1 mRNA expression and tumor depth of invasion (P=0.040). Furthermore, a significant correlation between lymph node metastasis and SIZN1 mRNA expression was observed in esophageal squamous cell carcinoma patients (P=0.036). Conclusion: This study is the first report that has assessed SIZN1 expression in esophageal squamous cell carcinoma patients. SIZN1 can be a potential therapeutic target for primary esophageal squamous cell carcinoma because of its role in the early stages of tumor progression and metastasis

Bi-allelic truncating variants in CASP2 underlie a neurodevelopmental disorder with lissencephaly

Lissencephaly (LIS) is a malformation of cortical development due to deficient neuronal migration and abnormal formation of cerebral convolutions or gyri. Thirty-one LIS-associated genes have been previously described. Recently, biallelic pathogenic variants in CRADD and PIDD1, have associated with LIS impacting the previously established role of the PIDDosome in activating caspase-2. In this report, we describe biallelic truncating variants in CASP2, another subunit of PIDDosome complex. Seven patients from five independent families presenting with a neurodevelopmental phenotype were identified through GeneMatcher-facilitated international collaborations. Exome sequencing analysis was carried out and revealed two distinct novel homozygous (NM_032982.4:c.1156delT (p.Tyr386ThrfsTer25), and c.1174 C > T (p.Gln392Ter)) and compound heterozygous variants (c.[130 C > T];[876 + 1 G > T] p.[Arg44Ter];[?]) in CASP2 segregating within the families in a manner compatible with an autosomal recessive pattern. RNA studies of the c.876 + 1 G > T variant indicated usage of two cryptic splice donor sites, each introducing a premature stop codon. All patients from whom brain MRIs were available had a typical fronto-temporal LIS and pachygyria, remarkably resembling the CRADD and PIDD1-related neuroimaging findings. Other findings included developmental delay, attention deficit hyperactivity disorder, hypotonia, seizure, poor social skills, and autistic traits. In summary, we present patients with CASP2-related ID, anterior-predominant LIS, and pachygyria similar to previously reported patients with CRADD and PIDD1-related disorders, expanding the genetic spectrum of LIS and lending support that each component of the PIDDosome complex is critical for normal development of the human cerebral cortex and brain function

Guanylyl Cyclase C as a tumor marker for detection of circulating tumor cells in the peripheral blood of colorectal cancer patients

Purpose: Guanylyl cyclase C (GCC) is one of the most frequent tumor markers to detect the circulating tumor cells (CTCs) in peripheral blood of colorectal cancer (CRC) patients. It has been proposed as a new marker for the molecular staging of CRC. The level of GCC mRNA expression in peripheral blood of CRC patients was evaluated to explore its probable correlations with the clinicopathological features.Methods: Relative quantitative expression analysis of GCC mRNA was performed on 80 blood samples (40 patients and 40 normal) using the Real-time RT-PCR.Results: GCC mRNA expression was detected in 70% of the CRC blood samples. The level of GCC mRNA expression in peripheral blood of patients was significantly higher than that in the normal cases (p = 0.031). Moreover, there was a significant correlation between the GCC copy number and advanced stages of tumor (p = 0.041). Furthermore, we have observed a significant correlation between tumor sizes and GCC copy numbers (p = 0.050).Conclusion: GCC can be a useful marker not only for detection of CTCs in CRC blood samples, but also for the molecular staging of colorectal cancer.

MicroRNAs as the critical regulators of Cisplatin resistance in ovarian cancer cells

Abstract Background Ovarian cancer (OC) is one of the leading causes of cancer related deaths among women. Due to the asymptomatic tumor progression and lack of efficient screening methods, majority of OC patients are diagnosed in advanced tumor stages. A combination of surgical resection and platinum based-therapy is the common treatment option for advanced OC patients. However, tumor relapse is observed in about 70% of cases due to the treatment failure. Cisplatin is widely used as an efficient first-line treatment option for OC; however cisplatin resistance is observed in a noticeable ratio of cases. Regarding, the severe cisplatin side effects, it is required to clarify the molecular biology of cisplatin resistance to improve the clinical outcomes of OC patients. Cisplatin resistance in OC is associated with abnormal drug transportation, increased detoxification, abnormal apoptosis, and abnormal DNA repair ability. MicroRNAs (miRNAs) are critical factors involved in cell proliferation, apoptosis, and chemo resistance. MiRNAs as non-invasive and more stable factors compared with mRNAs, can be introduced as efficient markers of cisplatin response in OC patients. Main body In present review, we have summarized all of the miRNAs that have been associated with cisplatin resistance in OC. We also categorized the miRNAs based on their targets to clarify their probable molecular mechanisms during cisplatin resistance in ovarian tumor cells. Conclusions It was observed that miRNAs mainly exert their role in cisplatin response through regulation of apoptosis, signaling pathways, and transcription factors in OC cells. This review highlighted the miRNAs as important regulators of cisplatin response in ovarian tumor cells. Moreover, present review paves the way of suggesting a non-invasive panel of prediction markers for cisplatin response among OC patients

Long non-coding RNAs as the critical regulators of PI3K/AKT, TGF-β, and MAPK signaling pathways during breast tumor progression

Abstract Breast cancer (BC) as one of the most common causes of human deaths among women, is always considered one of the global health challenges. Despite various advances in diagnostic and therapeutic methods, a significant percentage of BC patients have a poor prognosis due to the lack of therapeutic response. Therefore, investigating the molecular mechanisms involved in BC progression can improve the therapeutic and diagnostic strategies in these patients. Cytokine and growth factor-dependent signaling pathways play a key role during BC progression. In addition to cytokines and growth factors, long non-coding RNAs (lncRNAs) have also important roles in regulation of such signaling pathways. Therefore, in the present review we discussed the role of lncRNAs in regulation of PI3K/AKT, MAPK, and TGF-β signaling pathways in breast tumor cells. It has been shown that lncRNAs mainly have an oncogenic role through the promotion of these signaling pathways in BC. This review can be an effective step in introducing the lncRNAs inhibition as a probable therapeutic strategy to reduce tumor growth by suppression of PI3K/AKT, MAPK, and TGF-β signaling pathways in BC patients. In addition, considering the oncogenic role and increased levels of lncRNAs expressions in majority of the breast tumors, lncRNAs can be also considered as the reliable diagnostic markers in BC patients

Spontaneous adrenal hemorrhage during pregnancy: a case with horseshoe kidney

Spontaneous adrenal hemorrhage is an acute hemorrhage during pregnancy, which can be tragic for the mother and the baby. We report a unique spontaneous hemorrhage during pregnancy in a case with horseshoe kidney with separated adrenal, presented for the first time in the world. Computed tomography scan showed a horseshoe kidney fused with left normal kidney. Interestingly the adrenal gland was remained in right flank and separated from the horseshoe kidney, which prepares a probable physical stress for the hemorrhage. Diagnosis and surgery were done successfully and the case was fully recovered after several days