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Epstein–Barr virus (EBV) is the first identified human oncogenic virus that can establish asymptomatic life-long persistence. It is associated with a large spectrum of diseases, including benign diseases, a number of lymphoid malignancies, and epithelial cancers. EBV can also transform quiescent B lymphocytes into lymphoblastoid cell lines (LCLs) in vitro. Although EBV molecular biology and EBV-related diseases have been continuously investigated for nearly 60 years, the mechanism of viral-mediated transformation, as well as the precise role of EBV in promoting these diseases, remain a major challenge yet to be completely explored. This review will highlight the history of EBV and current advances in EBV-associated diseases, focusing on how this virus provides a paradigm for exploiting the many insights identified through interplay between EBV and its host during oncogenesis, and other related non-malignant disorders. [ABSTRACT FROM AUTHOR]

Objective: To determine the Carcinoembryonic Antigen Levels among patients with epithelial carcinoma presenting at a tertiary care hospital. Study Design: Prospective longitudinal study. Place and Duration of Study: Department of Medical Oncology, Jinnah Postgraduate Medical Centre, Karachi Pakistan, from May 2019 to May 2020. Methodology: Two hundred six patients presenting with a confirmed diagnosis of epithelial carcinoma, aged more than 15 years and of either gender were enrolled in the study. The CEA levels in all the patients were measured using an ELISA kit. The CEA levels were classified as 0-3.0 ng/mL, 3.1-5.0 ng/mL, 5.1-10 ng/mL and >10ng/mL. Results: The mean age of the cancer patients was estimated as 47.30±14.10 years. Most patients had rectum carcinoma 28(13.59%), followed by CA sigmoid 25(12.14%), respectively. The median CEA level was estimated as 5.80ng/mL ranging from 0.82 to 1000 ng/mL. About 76 patients had CEA level >10ng/mL (36.9%), 55 had CEA level 0-3.0 ng/mL (26.7%), 43 had CEA level 3.1-5.0ng/mL (20.9%), and 32 had CEA level 5.1-10.0ng/mL (15.5%). A statistically significant difference in proportions of CEA levels was found for histological type (p=0.001), type of cancer (p=0.001) and number of Mets (p=0.003). Conclusion: Rectal cancer profoundly expressed carcinoembryonic antigen levels, followed by sigmoid, colon, and ovarian cancer. Moreover, there is a significant association among carcinoembryonic antigen levels, histology, type and metastasis of cancer.

Epstein–Barr virus (EBV) is the first identified human oncogenic virus that can establish asymptomatic life-long persistence. It is associated with a large spectrum of diseases, including benign diseases, a number of lymphoid malignancies, and epithelial cancers. EBV can also transform quiescent B lymphocytes into lymphoblastoid cell lines (LCLs) in vitro. Although EBV molecular biology and EBV-related diseases have been continuously investigated for nearly 60 years, the mechanism of viral-mediated transformation, as well as the precise role of EBV in promoting these diseases, remain a major challenge yet to be completely explored. This review will highlight the history of EBV and current advances in EBV-associated diseases, focusing on how this virus provides a paradigm for exploiting the many insights identified through interplay between EBV and its host during oncogenesis, and other related non-malignant disorders.

Background: For patients with stage III epithelial ovarian cancer, there are limited studies on the effects of postoperative adjuvant radiotherapy (RT). Here we assessed the therapeutic efficacy and toxicity of postoperative radiotherapy to the abdominal and pelvic lymphatic drainage area for stage III epithelial ovarian cancer patients, who had all received surgery and chemotherapy (CT)., Methods: We retrospectively collected patients with stage III epithelial ovarian cancer after cytoreductive surgery (CRS) and full-course adjuvant CT. The chemoradiotherapy (CRT) group patients were treated with intensity modulated radiotherapy (IMRT) to the abdominal and pelvic lymphatic drainage area in our hospital between 2010 and 2020. A propensity score matching analysis was conducted to compare the results between the CRT and CT groups. Kaplan-Meier analysis estimated overall survival (OS), disease-free survival (DFS), and local control (LC) rates. The log-rank test determined the significance of prognostic factors., Results: A total of 132 patients with median follow-up of 73.9 months (9.1-137.7 months) were included (44 and 88 for the CRT and RT groups, retrospectively). The baseline characteristics of age, histology, level of CA12-5, surgical staging, residual tumour, courses of adjuvant CT, and courses to reduce CA12-5 to normal were all balanced. The median DFS time, 5-year OS, and local recurrence free survival (LRFS) were 100.0 months vs 25.9 months ( P = .020), 69.2% vs 49.9% ( P = .002), and 85.9% vs 50.5% ( P = .020), respectively. The CRT group mainly presented with acute haematological toxicities, with no statistically significant difference compared with grade III intestinal adverse effects (3/44 vs 6/88, P = .480)., Conclusion: This report demonstrates that long-term DFS could be achieved in stage III epithelial ovarian cancer patients treated with IMRT preventive radiation to the abdominal and pelvic lymphatic area. Compared with the CT group, DFS and OS were significantly prolonged and adverse effects were acceptable., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

SOX2 is a pleiotropic nuclear transcription factor with major roles in stem cell biology and in development. Over the last 10 years SOX2 has also been implicated as a lineage-specific oncogene, notably in squamous carcinomas but also neurological tumours, particularly glioblastoma. Squamous carcinomas (SQCs) comprise a common group of malignancies for which there are no targeted therapeutic interventions. In this article we review the molecular epidemiological and laboratory evidence linking SOX2 with squamous carcinogenesis, explore in detail the multifaceted impact of SOX2 in SQC, describe areas of uncertainty and highlight areas for potential future research. [ABSTRACT FROM AUTHOR]

Background: Rapid industrialization is discharging toxic heavy metals into the environment, disturbing human health in many ways and causing various neurologic, cardiovascular, and dermatologic abnormalities and certain types of cancer. The presence of arsenic in drinking water from different urban and rural areas of the major cities of Pakistan, for example, Lahore, Faisalabad, and Kasur, was found to be beyond the permissible limit of 10 parts per billion set by the World Health Organization. Therefore the present study was initiated to examine the effects of arsenite (As+3) on DNA biosynthesis and cell death. Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and flow cytometry. Results: We show that As+3 ions have a dose- and time-dependent cytotoxic effect through the activation of the caspase-dependent apoptotic pathway. In contrast to previous research, the present study was designed to explore the early cytotoxic effects produced in human cells during exposure to heavy dosage of As+3 (7.5 µg/ml). Even treatment for 1 h significantly increased the mRNA levels of p21 and p27 and caspases 3, 7, and 9. It was interesting that there was no change in the expression levels of p53, which plays an important role in G2/M phase cell cycle arrest. Conclusion: Our results indicate that sudden exposure of cells to arsenite (As+3) resulted in cytotoxicity and mitochondrial-mediated apoptosis resulting from up-regulation of caspases.

Objective: To determine the Carcinoembryonic Antigen Levels among patients with epithelial carcinoma presenting at a tertiary care hospital. Study Design: Prospective longitudinal study. Place and Duration of Study: Department of Medical Oncology, Jinnah Postgraduate Medical Centre, Karachi Pakistan, from May 2019 to May 2020. Methodology: Two hundred six patients presenting with a confirmed diagnosis of epithelial carcinoma, aged more than 15 years and of either gender were enrolled in the study. The CEA levels in all the patients were measured using an ELISA kit. The CEA levels were classified as 0-3.0 ng/mL, 3.1-5.0 ng/mL, 5.1-10 ng/mL and >10ng/mL. Results: The mean age of the cancer patients was estimated as 47.30±14.10 years. Most patients had rectum carcinoma 28(13.59%), followed by CA sigmoid 25(12.14%), respectively. The median CEA level was estimated as 5.80ng/mL ranging from 0.82 to 1000 ng/mL. About 76 patients had CEA level >10ng/mL (36.9%), 55 had CEA level 0-3.0 ng/mL (26.7%), 43 had CEA level 3.1-5.0ng/mL (20.9%), and 32 had CEA level 5.1-10.0ng/mL (15.5%). A statistically significant difference in proportions of CEA levels was found for histological type (p=0.001), type of cancer (p=0.001) and number of Mets (p=0.003). Conclusion: Rectal cancer profoundly expressed carcinoembryonic antigen levels, followed by sigmoid, colon, and ovarian cancer. Moreover, there is a significant association among carcinoembryonic antigen levels, histology, type and metastasis of cancer. [ABSTRACT FROM AUTHOR]

Introduction: Malignant serous effusions are common in metastatic carcinomas. Although cytomorphology is recognized as the gold standard diagnostic method, it exhibits moderate sensitivity. This study aimed to assess the diagnostic value of immunophenotyping with a single epithelial marker, known as the epithelial cell adhesion molecule (EpCAM, CD326), in discriminating malignant metastatic carcinomas of serous fluids., Methods: This prospective study was conducted on suspicious or confirmed cases of malignant tumors from September 16, 2019, to June 21, 2020. Serous fluid samples were assessed via cytomorphology using the Wright-Papanicolaou method and the anti-EpCAM mouse monoclonal antibody (clone VU-1D9) flow cytometry. The EpCAM(+)/CD45(-) immunophenotype was defined as the metastatic involvement of carcinoma in the serous cavity., Results: A total of 118 samples (90 females and 28 males; mean age, 54.04 ± 16.14 years), collected from peritoneal and pleural fluids, were examined in this study. Five samples (4.24%) were positive in both EpCAM flow cytometry and cytology, while 102 samples (86.44%) were negative for both EpCAM flow cytometry and cytology, yielding an overall agreement of 92%, 84%, and 90.7% for the peritoneal, pleural, and total samples, respectively. Based on the Bayesian latent class model, the EpCAM flow cytometry showed sensitivity and specificity of 58.5% (95% CI: 0.3, 99.7) and 96.2% (95% CI: 47.8, 100), respectively. The corresponding values were 68.7% (95% CI: 0.3, 99.9) and 96.1% (95% CI: 47, 100) for cytology, respectively., Conclusion: The EpCAM flow cytometry and cytology showed comparable performance in detecting metastatic effusions. The EpCAM flow cytometry might have a diagnostic value in decreasing the false-negative rate of cytomorphology, while maintaining excellent specificity., (© 2023 S. Karger AG, Basel.)

Neuropilin 1 (NRP1) is a transmembrane glycoprotein, which interacts with vascular endothelial growth factor to prevent tumor cell apoptosis and to regulate angiogenesis. However, the precise role of NRP1 in epithelial ovarian carcinoma (EOC) remains to be elucidated. The present study aimed to determine the association between NRP1 and EOC. The expression of NRP1 in ovarian cancer and normal ovarian epithelial tissues was investigated by immunofluorescence, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blotting. The association between the expression of NRP1 with the development of ovarian cancer, clinicopathological characteristics and survival were also analyzed. The results from immunofluorescence, RT-qPCR and western blot analysis demonstrated that NRP1 exhibited significant upregulation in EOC compared with normal ovarian epithelial specimens (P<0.05). The positive expression of NRP1 was higher in cancer tissues at an advanced International Federation of Gynecology and Obstetrics stage, and in cancer tissues with lymph node metastasis and distant metastasis compared with that in cancer tissues without lymph node or distant metastasis (P<0.05). Higher NRP1 expression strongly predicted a shorter survival time (P<0.001). The present findings suggested that increased NRP1 expression may be associated with the development of EOC. Therefore, NRP1 could be used as a valuable prognostic marker as well as a potential molecular therapy target for ovarian cancer patients. [ABSTRACT FROM AUTHOR]

Background: Rapid industrialization is discharging toxic heavy metals into the environment, disturbing human health in many ways and causing various neurologic, cardiovascular, and dermatologic abnormalities and certain types of cancer. The presence of arsenic in drinking water from different urban and rural areas of the major cities of Pakistan, for example, Lahore, Faisalabad, and Kasur, was found to be beyond the permissible limit of 10 parts per billion set by the World Health Organization. Therefore the present study was initiated to examine the effects of arsenite (As+3) on DNA biosynthesis and cell death. Methods: After performing cytotoxic assays on a human epithelial carcinoma cell line, expression analysis was done by quantitative polymerase chain reaction, western blotting, and flow cytometry. Results: We show that As+3 ions have a dose- and time-dependent cytotoxic effect through the activation of the caspase-dependent apoptotic pathway. In contrast to previous research, the present study was designed to explore the early cytotoxic effects produced in human cells during exposure to heavy dosage of As+3 (7.5 mg/ml). Even treatment for 1 h significantly increased the mRNA levels of p21 and p27 and caspases 3, 7, and 9. It was interesting that there was no change in the expression levels of p53, which plays an important role in G2/M phase cell cycle arrest. Conclusion: Our results indicate that sudden exposure of cells to arsenite (As+3) resulted in cytotoxicity and mitochondrial-mediated apoptosis resulting from up-regulation of caspases. [ABSTRACT FROM AUTHOR]

OBJECTIVE: It is known that the vacuolating cytotoxin (VacA) could induce apoptosis. However, the mechanism remained to be elucidated. The aim of this study is to investigate the role of Bcl family of proteins (Bcl-2 and Bax) and the mitochondrial voltage-dependent anion channel (VDAC) in VacA-induced apoptosis of AGS cells. METHODS: Plasmid pGBKT7-VacA p58 was constructed and transfected into the AGS cells. RT-PCR and Western blotting were used to determine the expressions of cytochrome c, caspase-3, Bax, Bcl-2 and VDAC1 mRNA and proteins. RESULTS: VacA p58 can induce cytochrome c release and activate caspase-3 in AGS cells. It up-regulated the expressions of Bax and VDAC1 mRNA and proteins, and decreased the expression of Bcl-2 in AGS cells. CONCLUSION: VacA p58 induces apoptosis in AGS cells. This apoptotic process is associated with the up-regulation of Bax/VDAC1 and downregulation of Bcl-2. These findings suggest that the release of cytochrome c by VacA p58 is mainly through VDAC-dependent and Bcl-2 family-dependent pathways. [ABSTRACT FROM AUTHOR]

Abstract: Advanced reflectance-based optical techniques for in vivo imaging often suffer from low contrast between neoplastic and normal tissue and are unable to image early biomolecular changes associated with carcinogenesis, thus limiting their clinical value. In this study, we exploit the resonance light scattering property of gold nanoparticles at their surface plasmon resonance to develop them as potential molecular contrast probes for imaging biomolecular changes during carcinogenesis under reflectance-mode imaging techniques. Gold nanoparticles were synthesized and conjugated to anti-epidermal growth factor receptor (EGFR). Their localization on the EGFR of nasopharyngeal carcinoma CNE2 cells and normal human lung fibroblast (NHLF) cells were imaged and compared under confocal microscopy in vitro. We have shown that the localization of gold bioconjugates on EGFR increases the reflectance properties of CNE2 cells and the regions of increased reflectance correspond to regions of high EGFR expression in the cells. The optical properties of normal fibroblast cells are not greatly affected. These gold bioconjugates are thus able to map the expression of relevant biomarkers and elicit an optical contrast for cancer cells over normal cells under confocal reflectance microscopy. Our study demonstrates the potential of gold nanoparticles to target and probe cancer cells and illuminates them for cancer detection under reflectance-based imaging systems based on biomolecular changes. [Copyright &y& Elsevier]

Worldwide, oral cancer is the sixth most common cancer for both sexes. In Singapore, the 5-year survival rate of oral cancer is about 50%. The high mortality rate has been attributed to the difficulties in detecting the disease in an early treatable stage. Here, we present two application examples of gold nanoparticles in the early detection of oral cancer. In the first, gold nanoparticles were used as a reflective contrast agent for performing molecular imaging under confocal reflectance microscopy for the early diagnosis of epithelial carcinoma. While in the second, closely-packed gold nanoparticle, films were used as a bio-sensing surface for the chemical analysis of saliva via Surface Enhanced Raman Scattering. Preliminary results will be discussed. [ABSTRACT FROM AUTHOR]

Abstract: Objective. – Ovulation induction, the usual resort of Assisted Reproductive Technologies (ART), has been suspected of carrying a responsibility in the genesis of ovarian tumours. For patients with a borderline or invasive ovarian tumour, treated by conservative surgery and desiring to become pregnant, the problem is thus of a possible resort to the Assisted Reproductive Technologies. Patients and methods. – This is a multicenter, national and retrospective study. 40 operated patients between January 1971 and January 2001 have been included. 27 patients (67.5%) had a borderline tumour, 10 (25%) a non-epithelial tumour (germinal or stromal) and 3 (7.5%) an epithelial invasive carcinoma. All these patients have benefited from a conservative surgical management of fertility. The Assisted Reproductive Technologies were simple stimulation for 5 women and IVF for the 35 others. The effectiveness and the risks of Assisted Reproductive Technologies have been estimated respectively by the number of pregnancies obtained and the recurrence rates. Results. – With a global follow-up of 372 months (January 1971: date of the primary surgical procedure – June 2002: closing of the study), 17 patients have obtained 17 pregnancies with the Assisted Reproductive Technologies, rate of 42.5% (17/40): 1 spontaneous abortion, 16 delivery with 23 children (triple pregnancies and 3 twin pregnancies). 3 patients treated for a borderline tumour have had a recurrence after induction of ovulation. Among the 40 patients, no one presented an evolved disease at the last news. The patients who had a recurrence had a delay to begin the Assisted Reproductive Technologies significantly lower than the patients who had no recurrence. Discussion and conclusion. – The assisted reproductive technologies for patients who had been treated for a borderline or invasive ovarian tumour, and who were infertile in spite of conservative management, have allowed 42.5% of these women to obtain a pregnancy and does not seem to increase significantly the risk of recurrence. [Copyright &y& Elsevier]

Abstracts: Allicin, the major component of Garlic (Allium sativum) was examined for the ability to induce apoptosis and the mechanism of the induction of apoptosis in human epithelial carcinoma cells. Allicin inhibited cell growth and induced apoptosis in gastric epithelial cells. Treatment with allicin resulted in morphological changes, DNA fragmentation, hypodiploid DNA contents and the translocation of Bax to mitochondria. The release of cytochrome c from mitochondria into the cytosol, which is an initiator of the activation of caspase cascades, was observed in allicin-treated cells. However, pretreatment with Z-Val-Ala-Asp-fluoromethylketone (Z-VAD-fmk), a broad spectrum of caspase inhibitor, could not rescue apoptotic cells from allicin toxicity. Coincidently, caspase-3 activation and cleavage of PARP were not detected. In addition, caspase independent apoptosis-inducing factor (AIF) was released from mitochondria after treatment with allicin. After pre-incubation of cells with the protein kinase A (PKA) inhibitor H-89, allicin was not capable of inducing an increase of the rate of apoptosis with affecting the expression levels of Bax and AIF. These data demonstrate that allicin induces a caspase-independent apoptotic pathway mediated by mitochondrial release of AIF and PKA appears to be involved in allicin-induced apoptosis in gastric epithelial cells. [Copyright &y& Elsevier]

Although it is generally believed that, under normal conditions, the only source of immunoglobulin is mature B lymphocytes, we recently found several epithelium-derived carcinoma cell lines also express immunolglobulin-like protein. We extended our study to biopsy samples of human cervical tissues with various epithelial lesions. By in situ hybridization, we only detected a low level of mRNA for the immunoglobulin kappa light chain constant region in epithelia with cervicitis. However, in epithelia with dysplasia and carcinoma, the expression of mRNA for the kappa constant region was markedly increased. There was no significant difference in the level of mRNA for the kappa constant region between epithelial dysplasia and carcinoma. The aberrant expression of immunoglobulin kappa light chain constant region in dysplastic and cancerous cervical epithelial cells may serve as a marker for malignant cell transformation. [Copyright &y& Elsevier]

Virulence factors produced by Helicobacter pylori have been known to be associated with serious gastroduodenal diseases. The aims of this study were to clarify the apoptosis-inducing properties of vacuolating cytotoxin (VacA) and examine the expression of apoptosis related proteins in human epithelial carcinoma cells expressing (AGS) or lacking (Kato III) p53. The midregion VacA homolog from H. pylori strain Q35 (Korean isolate) was cloned, expressed and sequenced. Recombinant VacA (VacA418–799) inhibited cell growth and induced apoptosis in gastric epithelial cells. Treatment with VacA418–799 resulted in morphological changes and DNA fragmentation. Cell cycle analysis revealed subdiploid cells suggesting apoptosis, which was confirmed by the activation of caspase-3 and cleavage of PARP. VacA418–799 also mediated a prolongation of the cell cycle progression in G1 phase. Furthermore, VacA418–799 increased the expression of p53, p21waf1/cip1 and Bax in AGS cells, but not in Kato III cells and did not affect the phosphorylation of Rb in both cell lines. These results indicate that recombinant VacA of H. pylori induces apoptosis in both Kato III and AGS cells, regardless of p53 status and suggest that VacA418–799 mediate the development of gastric diseases through cell cycle arrest in the G1 phase. VacA418–799 induction of apoptosis is associated with up-regulation of p53, p21waf1/cip1, Bax in AGS cells and activation of caspase-3 in both cell lines. [Copyright &y& Elsevier]

Cancer is the second most common culprit of mortality in the United States and epithelial carcinomas are considered as one of the most predominant types of cancer. The association between epithelial cancers and paired-box gene 8 (PAX8) has been studied significantly before. PAX8 belongs to the paired-box gene family, which plays an important role in the organogenesis of different body organ systems, especially the thyroid gland, the renal system, and the Müllerian system. Immunohistochemical staining is being used to detect PAX8 expression in different epithelial cancers and differentiate them from PAX8-negative tumors. In follicular, papillary, and anaplastic thyroid carcinomas, targeting the PAX8/peroxisome proliferator-activated receptors (PPARs) fusion protein is being considered as a potential mechanism for therapy. Moreover, because of its high expression in primary ovarian cancers, PAX8 is being considered as a target for ovarian cancer treatment as well. More studies are needed to test the possibility of using PAX8 as a possible target for managing endometrial carcinomas. In this article, we review the functions of the PAX8 gene, how its mutations lead to the development of certain epithelial carcinomas, how it can be used as a diagnostic or a prognostic marker, and its potential as a therapeutic target for these cancers., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Khizer et al.)

The appropriate regulation of spindle orientation maintains proper tissue homeostasis and avoids aberrant tissue repair or regeneration. Spindle misorientation due to imbalance or improper functioning leads to a loss of tissue integrity and aberrant growth, such as tissue loss or overgrowth. Pharmacological manipulation to prevent spindle misorientation will enable a better understanding of how spindle orientation is involved in physiological and pathological conditions and will provide therapeutic possibilities to treat patients associated with abnormal tissue function caused by spindle misorientation. N-terminal-deleted Rho guanine nucleotide dissociation inhibitor β (RhoGDIβ/RhoGDI2/LyGDI) produced by caspase-3 activation perturbs spindle orientation in surviving cells following exposure to either ionizing radiation or UVC. Thus, presumably, RhoGDIβ cleaved by caspase-3 activation acts as a determinant of radiation-induced spindle misorientation that promote aberrant tissue repair due to deregulation of directional organization of cell population and therefore becomes a potential target of drugs to prevent such response. The objective of this study was to screen and identify chemicals that suppress RhoGDIβ expression. We focused our attention on ascorbic acid (AA) derivatives because of their impact on the maintenance of skin tissue homeostasis. Here, we screened for AA derivatives that suppress RhoGDIβ expression in HeLa cells and identified a lipophilic derivative, 2-O-octadecylascorbic acid (2-OctadecylAA), as a novel RhoGDIβ inhibitor that ameliorated ionizing radiation-induced abnormal spindle orientations. Among all examined AA derivatives, which were also antioxidative, the inhibition activity was specific to 2-OctadecylAA. Therefore, this activity was not due to simple antioxidant properties. 2-OctadecylAA was previously shown to prevent hepatocellular carcinoma development. Our findings suggest that the anticarcinogenic effects of 2-OctadecylAA are partly due to RhoGDIβ inhibition mechanisms by which spindle orientation perturbations are attenuated. Thus, the molecular targeting features of RhoGDIβ warrant its further development for the treatment or control of spindle orientation abnormalities that affect epithelial homeostasis., (© 2021 Wiley Periodicals LLC.)