Emmanuel Kontomanolis

Serum and tissue LDH levels in patients with breast/gynaecological cancer and benign diseases.

Background: Lactate dehydrogenase A (LDHA) is involved in anaerobic glycolysis. In cancer patients, serum total lactate dehydrogenase (LDH) levels are often increased, and the gene for one of its isoenzymes, LDHA, is up-regulated. These features have been linked to poor prognosis in several studies. Methods: We investigated comparatively the total serum LDH activity and tissue isoenzyme LDH5 and hypoxia-inducible factor 1α (HIF1α) levels in patients with breast (n = 18) and gynaecological (n = 23) malignancies and benign diseases (n =54). Results: The serum LDH levels were significantly higher in patients with endometrial adenocarcinoma (349 ± 100 IU/l) and ovarian cystadenocarcinomas (383 ± 116 IU/l) compared to healthy controls (256 ± 68 IU/l) (p values 0.01 and 0.006, respectively). This difference did not reach significance in patients with breast cancer (328 ± 169 IU/l; p = 0.17)). Uterine leiomyoma patients showed intermediate LDH levels (310 ± 81 IU/l), while patients with breast fibroadenomas and ovarian cystadenomas had LDH serum levels close to carcinomas (308 ± 60 and 348 ± 135 IU/l, respectively). LDH5 isoenzyme was strongly expressed in cancer cells, exhibiting a mixed cytoplasmic/nuclear subcellular pattern. Interestingly, a high LDH5 content in tissue sections was not invariably accompanied by high LDH serum levels. High HIF1α tissue expression was linked to high tissue LDH5 expression. Conclusion: Serum and tissue LDH is up-regulated in gynaecologic and breast malignancies and in a subset of benign conditions such as fibro- and cystadenomas. The release of LDH, however, in the bloodstream is partly related to the LDHA gene up-regulation.

Association of −634G/C and 936C/T polymorphisms of the vascular endothelial growth factor with spontaneous preterm delivery

Background.  There is convincing evidence for a central role of vascular endothelial growth factor (VEGF) in fetal and placental angiogenesis. Our present study was undertaken to examine the possible relationship between two common functional VEGF gene polymorphisms (− 634G/C and 936C/T), linked with altered VEGF gene responsiveness, and spontaneous preterm delivery.

Serum VEGF levels and tissue activation of VEGFR2/KDR receptors in patients with breast and gynecologic cancer

OBJECTIVES Vascular endothelial cell growth factor (VEGF) plays an important role in the biology of gynecological cancer, usually linked with aggressive tumour behaviour and a poor postoperative outcome. Yet, its role in benign breast/gynecological conditions is less clear. METHODS Serum VEGF was analysed in a series of 49 patients with gynecological cancer and 61 patients with benign disease and compared to those of 12 normal female subjects. In addition, the activation status of VEGFR2/KDR receptors was investigated in formalin-fixed paraffin embedded tissues and related to VEGF. RESULTS Mean serum levels of VEGF were significantly higher in patients with breast, endometrial and ovarian cancer compared to healthy controls and those with benign breast/gynecologic disease in the respective organs. A similar trend was noted in some cases of simple endometrial hyperplasia, fibroadenoma and fibrocystic disease of the breast. The expression of phosphorylated VEGFR2/KDR receptors was higher in breast, endometrial, ovarian cancer in patients with high VEGF serum levels and this reached a level of statistical significance when all malignancies were combined. CONCLUSIONS Serum VEGF levels are increased in patients with breast and gynecological malignancies, but this can not be considered pathognomonic for cancer as it is also increased in certain benign conditions, including cases of fibroadenoma, fibrocystic disease of breast and simple endometrial hyperplasia. Furthermore, high serum VEGF levels are closely related to the activation status of the VEGFR2/KDR receptor in cancer cells, indicating a stimulatory effect of serum VEGF on the VEGF pathway contributing to tumor progression.

Overall survival and clinicopathological characteristics of patients with breast cancer in relation to the expression pattern of HER-2, IL-6, TNF-α and TGF-β1.

The present study was conducted to investigate the prognostic significance of co-expression patterna of HER-2, IL-6, TNF-a and TGF-β1 in breast cancer, by correlating the number of markers with positive expression with clinicopathological characteristics indicative of tumor progression and overall survival. One hundred thirty consecutive patients with primary breast cancer were prospectively included and evaluated. Serum concentrations of the above markers were measured by ELISA. Median split was used to subdivide patients with marker positive or negative expression. The presence of ≥ 3 positive markers was independently associated with extended lymph node (>3) involvement (aOR, 11.94, p=0.001) and lymphovascular invasion (aOR, 12.04, p=0.018), increasing the prognostic significance of each marker considered separately. Additional prognostic information regarding survival was also provided; as the number of positive markers increased, a gradually reduction of survival time was observed. In addition, patients with 4 positive markers had significantly shorter survival (25 vs 39 months, p=0.006) and a more than 4 fold increased risk of death (aHR, 4.35, p=0.003) compared to patients with 3 positive markers. Our findings suggest that the coexpression pattern of these four markers could be used clinically as a useful marker for tumor extension and outcome of breast cancer.

The social stigma of HIV-AIDS: society's role.

AIDS is a devastating and deadly disease that affects people worldwide and, like all infections, it comes without warning. Specifically, childbearing women with AIDS face constant psychological difficulties during their gestation period, even though the pregnancy itself may be normal and healthy. These women have to deal with the uncertainties and the stress that usually accompany a pregnancy, and they have to live with the reality of having a life-threatening disease; in addition to that, they also have to deal with discriminating and stigmatizing behaviors from their environment. It is well known that a balanced mental state is a major determining factor to having a normal pregnancy and constitutes the starting point for having a good quality of life. Even though the progress in both technology and medicine is rapid, infected pregnant women seem to be missing this basic requirement. Communities seem unprepared and uneducated to smoothly integrate these people in their societies, letting the ignorance marginalize and isolate these patients. For all the aforementioned reasons, it is imperative that society and medical professionals respond and provide all the necessary support and advice to HIV-positive child bearers, in an attempt to allay their fears and relieve their distress. The purpose of this paper is to summarize the difficulties patients with HIV infection have to deal with, in order to survive and merge into society, identify the main reasons for the low public awareness, discuss the current situation, and provide potential solutions to reducing the stigma among HIV patients.

The Notch Pathway in Breast Cancer Progression

Objective Notch signaling pathway is a vital parameter of the mammalian vascular system. In this review, the authors summarize the current knowledge about the impact of the Notch signaling pathway in breast cancer progression and the therapeutic role of Notchs inhibition. Methods The available literature in MEDLINE, PubMed, and Scopus, regarding the role of the Notch pathway in breast cancer progression was searched for related articles from about 1973 to 2017 including terms such as “Notch,” “Breast Cancer,” and “Angiogenesis.” Results. Notch signaling controls the differentiation of breast epithelial cells during normal development. Studies confirm that the Notch pathway has a major participation in breast cancer progression through overexpression and/or abnormal genetic type expression of the notch receptors and ligands that determine angiogenesis. The cross-talk of Notch and estrogens, the effect of Notch in breast cancer stem cells formation, and the dependable Notch overexpression during breast tumorigenesis have been studied enough and undoubtedly linked to breast cancer development. The already applied therapeutic inhibition of Notch for breast cancer can drastically change the course of the disease. Conclusion Current data prove that Notch pathway has a major participation and multiple roles during breast tumor progression. Inhibition of Notch receptors and ligands provides innovative therapeutic results and could become the therapy of choice in the next few years, even though further research is needed to reach safe conclusions.

Medicine from Ancient Times until Renaissance: Contributions of Early Physicians and the Impact of Religion

Great advancements in medicine and its many achievements are a fact for the modern civilizations. Religion coexists harmoniously with science while technology allows rapid access to an exchange of information, both playing an increasingly important role in the whole process of medical development. However, obstacles encountered by physicians were usually insurmountable and without them, the progress of science would have been undiminished. The established religious beliefs, non-progressive thinking, geopolitical imperialism, corruption, contributed many times to a misinterpretation on the original role of medicine, leading to a delay in medical progress. While being influenced by social and technological innovations, knowledge always prevented the medicine from stagnating and helped overcome differences between science and religion. The aim of this paper is to provide a survey on the contributions of some influential physicians and civilizations, and the role of religion on the evolution of medicine, from ancient times until the Renaissance.

Genetic variations in the SULF1 gene alter the risk of cervical cancer and precancerous lesions

Human papillomavirus (HPV) infection alone is not sufficient to explain the development of cervical cancer. Genetic variants have been linked to the development of precancerous lesions and cervical cancer. In this study, we aimed to evaluate the association of 10 single nucleotide polymorphisms (SNPs) of the Fas cell surface death receptor (FAS), trinucleotide repeat containing 6C (TNRC6C), transmembrane channel like 8 (TMC8), DNA meiotic recombinase 1 (DMC1), deoxyuridine triphosphatase (DUT), sulfatase 1 (SULF1), 2′-5-oligoadenylate synthetase 3 (OAS3), general transcription factor IIH subunit 4 (GTF2H4) and interferon gamma (IFNG) genes with susceptibility to precancerous lesions and cervical cancer. In total, 608 female participants, consisting of 199 patients with persistent low-grade precancerous lesions (CIN1), 100 with high-grade precancerous lesions (CIN2/3), 17 patients with cervical cancer and 292 healthy controls, were enrolled in this study. SNPs were tested for associations with each of the above-mentioned cervical group lesions or when considering an overall patient group. A significant difference for rs4737999 was observed between the controls and the overall patient group considering the recessive mode of inheritance [odds ratio (OR), 0.48; 95% confidence interval (CI), 0.24–0.96; P=0.033]. This effect was even stronger on the risk of CIN1 lesions. Carriers of the rs4737999 AA genotype were almost 3-fold less likely of having low grade lesions compared to the other genotypes. On the whole, this study provides evidence of an influence of the SULF1 gene rs4737999 SNP in the development of precancerous lesions/cervical cancer.

MicroRNAs as Potential Serum Biomarkers for Early Detection of Ectopic Pregnancy

Diagnosis of ectopic pregnancy relies on both ultrasound findings and human chorionic gonadotropin (hCG) measurements but due to the need for serial tests, tubal rupture and death represent major maternal and fetal risks. Early detection of ectopic pregnancy is essential and thus a noninvasive diagnostic tool seems crucial for the prevention of adverse effects since studies suggest there is a specific relationship between ectopic pregnancy and increasing microRNA factors. Human fluids in women with ectopic pregnancy reveal a particular change in comparison to healthy women. In addition to certain placental microRNAs circulating through plasma that present a specific concentration and serum profile, microRNAs seem to be possible biomarkers for the detection of pregnancy complications linked to placental pathologies. The aim of this study is to review current literature considering the expression levels of several circulating microRNAs that have shown to be novel potential biomarkers for the diagnosis of tubal ectopic pregnancy.

Increased Soluble PD-L1 Levels in the Plasma of Patients with Epithelial Ovarian Cancer Correlate with Plasma Levels of miR34a and miR200

Background: Recently, programmed cell death protein 1 (PD1) blocking and anti-programmed death-ligand 1 (PD-L1) agents were approved for the treatment of various human malignancies. Materials and Methods: Our study examined the expression of PD-L1 in neoplastic tissue (17 patients) and the plasma soluble (s)PD-L1 of 32 patients with ovarian carcinoma, in parallel with the levels of specific microRNAs (miRs), using immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively. Results: PD-L1 levels were significantly higher in the plasma of patients with ovarian cancer compared to healthy women (p=0.01). High miR200 levels were related to high sPD-L1 levels (p=0.03), whilst high miR34a levels were associated with low sPD-L1 levels (p=0.02). Immunohistochemical expression of PD-L1 by cancer cells was not related to plasma miR levels, nor to the level of sPD-L1. Conclusion: As well as cancer cell expression of PD-L1, a high sPD-L1 level characterizes a subset of patients with ovarian cancer. The value of this latter feature as a biomarker for the administration of anti-PD-L1/PD1 therapy needs further evaluation. Micro-RNAs, such as miR34a and miR200, may have a role in the efficacy of immunotherapy.