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COVID-19 has caused unprecedented societal turmoil, triggering a rapid, still ongoing, transformation of healthcare provision on a global level. In this new landscape, it is highly important to acknowledge the challenges this pandemic poses on the care of the particularly vulnerable cancer patients and the subsequent psychosocial impact on them. We have outlined our clinical experience in managing patients with gastrointestinal, hematological, gynaecological, dermatological, neurological, thyroid, lung and paediatric cancers in the COVID-19 era and have reviewed the emerging literature around barriers to care of oncology patients and how this crisis affects them. Moreover, evolving treatment strategies and novel ways of addressing the needs of oncology patients in the new context of the pandemic are discussed.

In light of the unprecedented public health crisis of the COVID-19 pandemic, it is highly important to acknowledge the psychological impact of this mounting threat on healthcare professionals. Previous experience from smaller scale epidemics and emerging literature around COVID-19 show that the unparalleled amount of stress that healthcare workers are dealing with, is associated with increased psychological morbidities. We have depicted the psychological burden that the COVID-19 pandemic has posed on healthcare professionals in Greece and have reviewed the literature around the effect of previous epidemics on frontline healthcare staff. Moreover, we discuss potential triggers and the need for measures to minimise the psychological pressure on those at the frontline against this biothreat.

Background: Endothelial cells, monocytes/macrophages, and vascular smooth muscle cells contribute to the establishment and progression of atherosclerotic lesions by expressing growth and inflammatory factors. The aim of the present study was to determine whether heregulin (HRG) is associated with human coronary artery disease. Methods: Twenty-six fresh human coronary artery segments were collected at autopsy. Expression of cysteine-rich 61 (CYR61) and VEGF in response to HRG was studied in the human endothelial cell line EA. hy926, and expression of CYR61 and HRG was evaluated in activated macrophages isolated from peripheral blood of healthy donors. Results: We found that HRG was overexpressed at the protein and mRNA level in all lesions analyzed and gradually increased as the stages of the lesions progressed. Expression of HRG was observed in the intima primarily in macrophages. The same specimens were analyzed for the expression of CYR61, an angiogenetic factor regulated by HRG in breast cancer epithelial cells. CYR61 was expressed in both normal and atheromatic specimens, but its expression was significantly enhanced in macrophages of the intima. Activation of primary human macrophages results in increased expression of both HRG and CYR61. In addition, studies in endothelial cells where no endogenous HRG is present showed that HRG induces expression of CYR61 and secretion of VEGF. Conclusions: HRG may, therefore, play an important role in the development of coronary artery disease and the expansion of the atherosclerotic plaque and may locally regulate the expression of the angiogenetic factor CYR61. Copyright (C) 2005 S. Karger AG, Basel.

Background Nonmelanoma skin cancers [squamous cell carcinomas (SCC) and basal cell carcinomas (BCC)] are the most common neoplasias of the Caucasian population. Objectives The purpose of our study was to determine the involvement of CDKN2A genes in the development of sporadic nonmelanoma skin cancer in Greek patients. Patients and methods Allelic imbalance analysis was performed in 22 SCC and five Bowen’s disease specimens. Mutational analysis was performed on exons 1alpha, 1beta and 2 of the CDKN2A locus in 22 SCC, five Bowen’s disease and 39 BCC specimens. Exon 1alpha was additionally screened in 28 BCC specimens to complete the mutational analysis of a previous study. Results Overall, 52% (14 of 27) of the SCC and Bowen’s disease specimens exhibited loss of heterozygosity (LOH) in at least one microsatellite marker, whereas, only two of 27 (7%) exhibited microsatellite instability. LOH in 9p appears to be equally involved in both BCC and SCC tumours. Exons 1alpha, 1beta and 2 of the CDKN2A locus were screened for mutations. A Val28Gly substitution in exon 1alpha and a CCC–>TTT (Ala57Val and Arg58Ter) substitution in exon 2, resulting in a change in the amino acid sequence, are reported for the first time in two SCCs, the latter being indicative of a combination of an ultraviolet (UV) radiation-induced mutation and a point mutation. A previously described polymorphism of CDKN2A, the gene for p16(INK4a) , Ala148Thr, was also detected in an allelic frequency of 3.72%. No mutation was found in any of the five Bowen’s disease specimens, or in exon 1beta of CDKN2A , also the gene for p14(ARF) . Conclusions Mutations and the high incidence of 9p LOH detected in our SCC samples imply that inactivation of CDKN2A genes, via allelic loss and/or mutation (probably UV-induced) may play a significant role in nonmelanoma skin cancer development, particularly in the more aggressive SCC type.

Basal cell carcinoma of the skin is the most common neoplasia in humans. Previous studies have shown the existence of allelic imbalance (loss of heterozygosity and microsatellite instability) in BCC on several human chromosomes. Chromosome region 9p21-p22 harbors the CDKN2a/16(INK4a), p19(ARF), and p15(INK4b) tumor suppressor genes. To determine the contribution of these genes to the development of basal cell carcinomas we looked for evidence of allelic imbalance in 67 sporadic basal cell carcinoma specimens from Greek patients and screened 28 of them presenting loss of heterozygosity at 9p21-p22 for germline mutations in p16(INK4a) and p19(ARF) genes. Chromosome regions 17q21 and 17p13 were also screened for allelic imbalance in all the 67 basal cell carcinoma specimens. Overall, 69% (46 of 67) of the specimens displayed loss of heterozygosity in at least one microsatellite marker, whereas only six of the 67 (9%) exhibited microsatellite instability. For the 9p21-p22 locus the overall frequency of loss of heterozygosity reached 55% (37 of 67) and is the highest reported. The overall frequency of loss of heterozygosity for the 17q21 locus is 34% (22 of 64) and for the 17p13 locus is 11% (seven of 65). Two of the 28 loss of heterozygosity positive cases were heterozygous for a previously described polymorphism, Ala148Thr, in exon 2 of the CDKN2a gene. This is the first demonstration of polymorphism in the CDKN2a gene in human basal cell carcinomas. No sequence variation in exon 1 beta of the p19(ARF) gene was found. Our results provide evidence of a significantly high occurrence of loss of heterozygosity for the 9p21-p22 locus; however, lack of p16(INK4a)/p19(ARF) mutation suggests that these genes seem not to be implicated by mutational inactivation in the development of basal cell carcinoma. Other(s), yet unidentified, tumor suppressor gene(s) located in this locus may be related to this specific type of skin cancer.

Human papilloma viruses (HPVs) consist of more than 70 different types and are known to be associated with numerous malignant tumors, including carcinomas of the mucosal and cutaneous epithelium. Non-melanoma skin carcinoma (NMSC) is the most frequently occurring malignancy worldwide in the Caucasian population. Most studies examining the involvement of papillomaviruses in the development of cutaneous carcinomas have been performed on lesions from patients with epidermodysplasia verruciformis or from immunosuppressed patients. Our specimens were obtained from 108 immunocompetent patients with benign and malignant skin lesions, and HPVs were detected in 27%. HPV 8 and HPV 18 were the most frequent types (62 and 48%, respectively). Our results suggest that HPVs, particularly the oncogenic potential of certain types such as HPV 8, 18, and 5 could contribute to the development of NMSCs. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.

In epithelial ovarian neoplasms K-ras codon 12 gene mutations show a wide variation fluctuating between 4-39% in invasive carcinomas and 20-48% in borderline malignant tumors. In this study, we showed the pattern of point mutations in codon 12 of the K-ras, H-ras and N-ras genes, using polymerase chain reaction restriction fragment length polymorphism analysis in 74 tissue specimens of Greek patients with epithelial ovarian tumors. K-ras and H-ras gene mutations were detected in 11/48 (23%) and 3/48 (6%) cases with primary invasive ovarian carcinomas, respectively, while N-ras gene mutations were not found. No mutation of K-, H- and N-ras genes was detected in 23 ovarian cystadenomas. in 1 out of 3 borderline ovarian tumors (33%) we found an H-ras gene mutation. The prevalence of mutations in K-ras gene was 1/8 (13%) in mucinous, 7/29 (24%) in serous, 1/3 (33%) in endometrioid and 2/8 (25%) in clear-cell adenocarcinomas and in H-ras gene 1/8 (13%) in mucinous and 2/29 (7%) in serous adenocarcinomas. Analysis of the results revealed no significant correlation between ras gene mutations and clinicopathological parameters or clinical outcome of this primary invasive ovarian carcinoma population. Our present data suggest that ras gene mutations in invasive ovarian carcinomas occur in 29% of Greek patients and are not associated with the differentiation of the epithelial cells or the response of patients to adjuvant platinum-based chemotherapy.

To determine the prevalence of activated ras-oncogenes (N-ras, Harvey-ras Kirsten-ras), DNA derived from peripheral blood of 51 patients with myelodysplastic syndrome (MDS) was investigated, The method was based on the polymerase chain reaction (PCR) technique to amplify DNA, followed by restriction fragment length polymorphism (RFLP) analysis, Among the French-American-British (FAB) subtypes, N-ras mutations were found in two patients with refractory anemia with excess of blasts (RAEB), in one patient with refractory anemia with excess of blasts in transformation (RAEB-t), and in two patients with chronic myelomonocytic leukemia (CMML). MDS patients with a mutation at codon 12 of the N-ras gene showed shorter survival duration than other MDS patients of the same FAB subtypes, although these findings proved to be not statistically significant (P > 0.1). Interestingly, all but one patient with N-ras mutation developed acute myelogenous leukemia (AML). In conclusion, the presence of mutation at codon 12 of the N-ras gene might serve as a negative prognostic factor at diagnosis of MDS.

The hypothesis of a primary action of steroid hormones on mitochondrial gene expression has been supported by the detection of the glucocorticoid receptor in liver mitochondria and the demonstration of the interaction of the receptor with putative mitochondrial HREs. We now show that two putative mitochondrial glucocorticoid response elements present within the cytochrome oxidase subunit I gene (GREI and GREII), linked to a thymidine kinase promoter and to the CAT gene, transfected to LATK(-) cells, confer dexamethasone inducibility to the CAT gene. As the plasmids were stably transfected, hormone induction was analysed in the nuclear background. This effect is dose dependent and is abolished by the glucocorticoid antagonist RU38486. (C) 1997 Academic Press.

We used the PCR technique to detect the Epstein-Barr virus (EBV) and human papillomavirus (HPV) DNA in paraffin-embedded tissues from Greek patients with nasopharyngeal carcinoma (NPC). The oligonucleotide primers used for the detection of EBV amplify a 375-bp long sequence from the EcoRI B fragment of the viral genome, whereas for HPV the primers amplify a 151-bp long sequence of the viral genome. The PCR products were analysed by agarose gel electrophoresis and visualised by UV illumination after staining with ethidium bromide. Sixty-three specimens were examined. EBV specific sequence was amplified in 20 (32%) and HPV in 12 (19%) out of the 63 samples. There was no co-infection with EBV and HPV. Although there is a high correlation of EBV infection with poorly differentiated NPC in patients from Southern China and South-East Asia, the restricted distribution suggests genetic or environmental cofactors in the development of the neoplasm. Our results confirm this suggestion since there was only a 32% correlation of EBV with NPC in Greece. HPV may also be involved in the carcinogenesis of EBV-negative squamous cell nasopharyngeal carcinomas.

The class I growth factor receptor family includes epidermal growth factor receptor, i.e. c-erbB-1, c-erbB-2 and c-erbB-3 molecules. These receptors have a significant sequence homology and play an important role in cell growth and differentiation. To further investigate their implication in squamous cell lung carcinomas (SqCLCs), we studied the protein expression by immunohistochemistry and examined for possible gene amplification by a novel semi-quantitative differential polymerase chain reaction (DPCR) technique. Expression of c-erbB-1, c-erbB-2 and c-erbB-3 was present in 65%, 28% and 10% respectively, of 40 SqCLCs cases. Seven of the 11 cases that expressed c-erbB-2, was well as all 4 c-erbB-3 expressing cases, also stained with the anti-c-erbB-1 mAb. Expression of c-erbB-1, but not c-erbB-2 or c-erbB-3, correlated with the grade of tumor differentiation (100%, 64% and 36% positive cases of well, moderately and poorly differentiated cases respectively, p < 0.003). In addition, c-erbB-1 expression correlated with the presence of regional lymph node metastases within the moderately differentiated group. The c-erbB-1 gene was amplified in 11/40 (28%) cases, all of which overexpressed c-erbB-1 protein, while c-erbB-2 gene amplification was detected in only one case. There was no c-erbB-3 gene amplification in any of the 40 SqCLCs cases. These findings suggest that c-erbB-1, c-erbB-2 and c-erbB-3 receptors do not have a common role and are of different physiological importance, at least at the stage of clinically overt tumor in human SqCLCs.

Epstein-Bar virus (EBV) is a B-lymphotropic virus with a tumorigenic potential. EBV infection has been recognized as rite main cause of nasopharyngeal carcinoma and Burkitt’s lymphoma. The aim of our study was to determine the incidence of EBV in squamous cell carcinomas of the larynx. We employed for our analysis a sensitive polymorphism chain reaction (PCR) assay, followed by restriction fragment length polymorphism (RFLP) for further confirmation of the specificity of the PCR-amplification reaction, Our analysis revealed that 9 of 27 (33%) specimens harbored the EBV genome in the tumor tissue while only 4 (15%) specimens from adjacent normal tissue exhibited evidence of EBV infection. Three were EBV positive for both normal and tumor tissue. No association has been found with disease stage, histological differentiation and nodes at pathology. The relatively high incidence of EBV in the tumor tissue (33%) of patients with laryngeal cancer, as compared to the low (15%) incidence of the virus genome detected in the adjacent normal tissue of the patients, indicates a probable role of EBV in the development of the disease.

Epidermal growth factor (EGF) and its receptor (EGFr) constitute an important and well-characterized mitogenic system in various ectodermal tissues. We evaluated the expression of EGFr and examined possible EGFr gene alterations in 18 formalin-fixed, paraffin-embedded squamous cell lung carcinomas (SCLC) by an immunohistochemical assay, Southern blotting and differential polymerase chain reaction (DPCR). The immunohistochemical study employing the F4 and EGF-R1 monoclonal antibodies, directed against the intra- and extra-cellular portion of the receptor respectively, showed EGFr over-expression in 89% of the SCLC cases examined. All cases showed positive immunostaining for both antibodies, thus excluding the possibility of truncated receptors. In addition, analysis of the EGFr gene was carried out by Southern blotting and DPCR on paraffin extracted DNA from the same carcinoma cases. We found amplification of the EGFr gene in 5/18 (27%) SCLCs. All 5 positive cases showed EGFr over-expression, suggesting a possible correlation between the presence of EGFr gene amplification and over-expression of receptor protein. No correlation was observed among EGFr staining, EGFr gene amplification and differentiation of carcinomas. In addition, Southern blot analysis with HER-A2, a probe which hybridizes a sequence of the receptor’s intracellular domain, revealed three novel EcoRI restriction fragment patterns. We suggest that these patterns correspond to EcoRI polymorphic sites of the receptor’s tyrosine kinase domain.