Dimitrios Kanakis | University of Nicosia (original) (raw)

Papers by Dimitrios Kanakis

Techniques in neurosurgery & neurology, Aug 22, 2017

Desmoplastic non-infantile ganglioglioma (DNIG) is a rare tumor entity and only a small number of... more Desmoplastic non-infantile ganglioglioma (DNIG) is a rare tumor entity and only a small number of cases have been published until now in the literature. Although its infantile counterpart (desmoplastic infantile ganglioglioma [DIG]) has been already recognized and included together with desmoplastic infantile astrocytoma (DIA) in the WHO Classification of CNS tumors, DNIG has not been accepted as a distinct tumor entity. The reason for this is obviously the scarcity of the neoplasm and subsequently the absence of substantial information regarding its pathogenesis and its association to the infantile form. Herein we present an interesting case with an unremarkable clinical presentation, which came to medical attention after the performance of imaging investigations, for staging purposes of a multifocal papillary thyroid carcinoma. Although the tumor showed the typical biphasic nature, consisting of a solid and a cystic component, its localization in the left ventricular trigonum, was indeed uncommon. Finally, both the histomorphological and the immunohistochemical findings were consistent with the diagnosis of a desmoplastic non-infantile gangioglioma. The occurrence of DNIG with the various clinical manifestations as well as the diverse imaging features, underlines the need of histopathological examination, in order to establish the final diagnosis.

Biomedicines

The global outbreak of SARS-CoV-2/COVID-19 provided the stage to accumulate an enormous biomedica... more The global outbreak of SARS-CoV-2/COVID-19 provided the stage to accumulate an enormous biomedical data set and an opportunity as well as a challenge to test new concepts and strategies to combat the pandemic. New research and molecular medical protocols may be deployed in different scientific fields, e.g., glycobiology, nanopharmacology, or nanomedicine. We correlated clinical biomedical data derived from patients in intensive care units with structural biology and biophysical data from NMR and/or CAMM (computer-aided molecular modeling). Consequently, new diagnostic and therapeutic approaches against SARS-CoV-2 were evaluated. Specifically, we tested the suitability of incretin mimetics with one or two pH-sensitive amino acid residues as potential drugs to prevent or cure long-COVID symptoms. Blood pH values in correlation with temperature alterations in patient bodies were of clinical importance. The effects of biophysical parameters such as temperature and pH value variation in ...

The Breast, 2019

course and outcomes in triple negative breast cancer patients in our tertiary care centre in the ... more course and outcomes in triple negative breast cancer patients in our tertiary care centre in the most populous state of India. Methods: A retrospective review of data from 972 breast cancer patients treated at our centre from 2010 to 2017 was conducted. Metastatic cases were excluded. Subtypes were defined based on immunohistochemistry(IHC)-estrogen/progesterone receptor, human epidermal growth factor receptor (Her2). Surgery included breast conserving surgery or modified radical mastectomy. Taxane & anthracycline based chemotherapy and external body radiotherapy were given as indicated. Epidemiological, clinical and outcome data was analysed using SPSS v24. Results: A total of 638 operable breast cancer patients were treated at the centre from 2010 to 2017. Mean age was 42.8 years (range 22-74). Based on IHC, 273 (42.8%) patients had triple negative breast cancer (TNBC), compared with luminal A (162), luminal B (97) & Her 2 rich (106). Among the TNBC patients, 48% of the patients were premenopausal & 2 patients were nulliparous. Early breast cancer (n = 125) patients underwent primary surgery. Locally advanced cases (n = 148) underwent neo-adjuvant chemotherapy (NACT). The response to chemotherapy was complete in 3.2%, partial in 35.6%; 46.2% had stable disease, 12.5% had progression; remaining 2.5% discontinued treatment. Total 242 underwent surgery. Nodes were positive in 58%. Median follow up was 2.8 years. Post operative locoregional recurrences in 12 patients & distant recurrences (mostly in lung) in 27 patients were noted. Death due to other causes was noted in 10, death due to disease in 22 patients & loss of follow up in 8 patients. 3-year disease free survival was 50.6%. Conclusions: The incidence of breast cancer in the present study is at a lower age as compared to the western population. Triple negative breast cancer disease is the most common subtype observed in the present population, unlike western studies where luminal A is the most common. As opposed to the widely documented good response to chemotherapy in TNBC, the present study noted a poor response in these patients, which may be attributed to the advanced stage at presentation in the Indian population. Conflict of Interest: No significant relationships.

Pituitary Adenoma: Pathophysiology, Diagnosis and Treatment Options

Frontiers in Molecular Biosciences, 2021

The collagen-integrin interactions are mediated by the doubly charged Mg2+ cation. In nature this... more The collagen-integrin interactions are mediated by the doubly charged Mg2+ cation. In nature this cation seems to have the optimal binding strength to stabilize this complex. It is essential that the binding is not too weak so that the complex becomes unstable, however, it is also of importance that the ligand-receptor binding is still labile enough so that the ligand can separate from the receptor in a suited environment. In the case of crystal growing for experimentally useful integrin-collagen fragment complexes it turned out that Co2+ cations are ideal mediators to form stable complexes for such experiments. Although, one can argue that Co2+ is in this context an artificial cation, however, it is now of special interest to test the impact of this cation in cell-culture experiments focusing on integrin-ligand interactions. In order to examine, in particular, the role cobalt ions we have studied a Co2+ based model system using quantum chemical calculations. Thereby, we have shown ...

Piriformis syndrome – an attempt to understand its pathology

Clinical Neuropathology, 2010

OBJECTIVE Gross anatomy of the hip rotators and histology of the sciatic nerves in adult cadavers... more OBJECTIVE Gross anatomy of the hip rotators and histology of the sciatic nerves in adult cadavers were studied, aiming to the identification of possible pathologic changes related to the piriformis syndrome (PS). MATERIAL 50 cadavers were dissected; in 17 cases with macroscopical findings the sciatic nerves were harvested (34 sciatic nerves; 17 cadavers). History of low back or leg pain was not available. METHOD Site anatomy and additional findings at the harvesting sites were recorded, such as anatomical variations, adhesions, hematomas etc. All nerves were additionally microscopically analyzed. In cases with findings at the dissection, the contralateral unaffected nerves served as controls. All the dissected nerves were conserved in 10% formalin solution, embedded in paraffin, stained with Hematoxylin and Eosin (H&E) and immunolabeled with antibodies against Neurofilament (NF). RESULTS Both the H&E staining as well as the performed immunohistochemistry showed, to a variable degree, significant alterations in the structure of the affected nerves compared to the controls. CONCLUSIONS These findings both in the local anatomy and sciatic nerve correspond to lesions that are expected in PS. Nevertheless, since this was a cadaveric study, unassociated to a certain pain patient's history, results should be considered and interpreted as an indication of a sciatic nerve injury in PS.

Brain Pathology, 2018

1 Pathology Department, Medical School, Aristotle University, Thessaloniki, Greece. 2 Pathology D... more 1 Pathology Department, Medical School, Aristotle University, Thessaloniki, Greece. 2 Pathology Department, “Papageorgiou” General Hospital, Thessaloniki, Greece. 3 Department of Molecular Biology and Genetics, Health Sciences School, Democritus University of Thrace, Alexandroupolis, Greece. 4 Radiology Department, “Papageorgiou” General Hospital, Thessaloniki, Greece. 5 University of Nicosia Medical School, Nicosia, Cyprus.

Pilocytic astrocytoma is considered by the WHO classification of the CNS tumors (2007) as a benig... more Pilocytic astrocytoma is considered by the WHO classification of the CNS tumors (2007) as a benign neoplasm (grade I), whereas the same taxonomy applies to anaplastic astrocytoma a high grade of malignancy (grade III). The occurrence of tumors combining both features of pilocytic and anaplastic astrocytomas has been already described previously in a few case reports. Herein, we present the case of a three years old boy, who presented signs and symptoms consistent with obstructive hydrocephalus caused by an intracerebellar sited neoplasm. The latter demonstrated both solid and cystic areas and contrast enhancement in the performed magnetic resonance imaging (MRI). The microscopic evaluation of the excised specimens showed the typical biphasic pattern of pilocytic astrocytoma together with Rosenthal fibers, eosinophilic granular bodies (EGBs) and hyaline droplets but also anaplastic features such as hypercellularity, endothelial proliferation, high mitotic index and focal necrosis. Du...

Update on the Anti-Cancer Potency of Tocotrienols and α-Tocopheryl Polyethylene Glycol 1000 Succinate on Leukemic Cell Lines

Nutrition and Cancer, 2020

Abstract The natural isoforms of vitamin E γ-tocotrienol (γ-ΤΤ) and δ-tocotrienol (δ-ΤΤ) and the ... more Abstract The natural isoforms of vitamin E γ-tocotrienol (γ-ΤΤ) and δ-tocotrienol (δ-ΤΤ) and the synthetic derivative α-tocopheryl polyethylene glycol 1000 succinate (TPGS) have promising anticancer potency in a variety of cancer cell lines and animal models of cancer. Ongoing clinical trials are investigating the anti-tumor effectiveness of TTs in combination with chemotherapeutic agents in patients suffering from breast, colon, non-small cell lung and ovarian cancers. Despite extensive research on different types of cancer, the anticancer potency of TTs and TPGS has not been thoroughly investigated in leukemias. Given the fact that certain types of leukemias have very low survival rates and that patients suffer significantly from the toxic side effects of chemotherapeutic drugs, there is a need to develop novel treatments with increased specificity against cancer cells and reduced toxicity to the patients. The aim of this review is to report current evidence on the anticancer potency of TTs and TPGS on leukemic cells lines and to discuss future studies that could be carried out to investigate the role of these agents in the management of leukemias.

APMIS, 2018

This study essentially aims to contribute to the immunohistochemical investigation of the use of ... more This study essentially aims to contribute to the immunohistochemical investigation of the use of pituitary tumor transforming gene (PTTG) as a marker of cell proliferation or advanced tumor grade in meningiomas of various WHO grades. In all, 51 cases were recovered in total, 21 Grade-I, 23 Grade-II and 7 Grade-III meningiomas. Mitotic index (MI), Ki-67/MiB-1 positivity percentage and PTTG expression were analyzed in correlation to each other as well as to the tumor WHO grades. All three biomarkers showed a high diagnostic significance and a strong association with WHO grades. In comparison, PTTG expression was on a par with the other two indices, and performed very well regarding identification of advanced grade tumors. PTTG may be considered an important diagnostic tool and serve in the future as a novel prognosticator of the biological behavior of all grade meningiomas as well as a useful high-risk patient selection tool.

European Journal of Nutrition, 2019

Despite significant advances in the diagnosis and treatment of cancer, the latter still remains a... more Despite significant advances in the diagnosis and treatment of cancer, the latter still remains a fatal disease due to the lack of prevention, early diagnosis, and effective drugs. Radiotherapy, chemotherapy, and surgery are not only expensive but produce a number of side effects that are detrimental to the patients' quality of life. Therefore, there is a great need to discover anti-cancer therapies that are specific to cancer cells and affordable, safe, and well tolerated by the patients. Vitamin E is a potential candidate due to its safety. Accumulating evidence on the anti-cancer potency of vitamin E has shifted the focus from tocopherols (TOCs) to tocotrienols (TTs). γ-TT and δ-TT have the highest anti-cancer activities and target common molecular pathways involved in the inhibition of the cell cycle, the induction of apoptosis and autophagy, and the inhibition of invasion, metastasis, and angiogenesis. Future directions should focus on further investigating how γ-TT and δ-TT (solely or in combination) induce anti-cancer molecular pathways when used in the presence of conventional chemotherapeutic drugs. These studies should be carried out in vitro, and promising results and combinations should then be assessed in in vivo experiments and finally in clinical trials. Finally, future research should focus on further evaluating the roles of γ-TT and δ-TT in the chemoprevention of cancer.

Journal of Neuro Oncology, Nov 1, 2003

The purpose of this study was to investigate the potential effects of epothilones (EPOs), a new c... more The purpose of this study was to investigate the potential effects of epothilones (EPOs), a new class of microtubule stabilizing cytotoxic drugs, on glioma cells in vitro. The effects of 1, 10 and 100 nM concentrations of EPO D in four malignant human glioma cell lines were measured using a microtiter-tetrazolium assay. Besides the cell lines U87MG, U138MG and LN405, one cell line was used, which had been derived from a recurrent and therapy-resistant glioblastoma in our laboratory. In addition, changes of the cell morphology were followed by light microscopy and changes in the microtubule and actin cytoskeleton were visualized by a confocal laser microscope. In all four human glioma cell lines, 10 and 100 nM concentrations of the drug, applied for 96 h, lead to a highly significant decrease in the viable cell number (p < 0.001). A mean reduction of the viable cell number between 30% and 40% (60% and 90%) was observed for a drug concentration of 10 nM (100 nM). A round cell morphology occured in most EPO treated cells and the organized network of microtubules was shrunk in these round cells. The tubulin immunostaining now appeared amorphous and was restricted to small perinuclear regions. Large actin filaments also disappeared, but actin staining was present in the whole cytosplasm. These results prove that EPOs have antiproliferative effects in glioma cells and affect their tubulin cytoskeleton, as it was previously observed in several types of carcinoma cells.

Human Pathology, Jan 31, 2003

Gliomatosis cerebri (GC) is a rare neuroepithelial tumor characterized by diffuse infiltration of... more Gliomatosis cerebri (GC) is a rare neuroepithelial tumor characterized by diffuse infiltration of large parts of the brain. The origin of GC is unknown, and the molecular alterations underlying this tumor have not been determined. Because mutations in the p53 tumor-suppressor gene are frequent in common gliomas, we investigated the distribution of p53 alterations by immunohistochemistry and direct sequencing in a GC case with a disease involving both hemispheres and the basal ganglia. Nuclear accumulation of p53 protein was detected in a single region with features of a high-grade glioma. In the remaining 10 regions, corresponding to low-grade gliomas, no p53 accumulation was seen. In 1 low-grade tumor sample, a pathogenic splice site mutation was detected. These findings suggest that p53 alterations occur in GC, but are no prerequisite of malignant progression. The distribution of p53 alterations demonstrates the existence of topographically different clones in 1 patient. HUM PATHOL 34:102-106.

Transcripts of PTTG and Growth Factors bFGF and IGF-1 are Correlated in Pituitary Adenomas

Experimental and Clinical Endocrinology Diabetes, 2010

The reasons for the increase of pituitary tumor-transforming gene (PTTG) transcripts in about 90%... more The reasons for the increase of pituitary tumor-transforming gene (PTTG) transcripts in about 90% of pituitary adenomas are still not fully understood, although upregulation by basic fibroblast growth factor (bFGF) has been discussed as a potential cause. A possible influence of the Insulin like Growth Factor 1 (IGF-1) might be of interest, since this protein is also synthesized in most pituitary adenomas. Moreover, the principal regulation of the PTTG gene by IGF-1 and Insulin has been demonstrated in astrocytoma and breast cancer cells. We analyzed a large group (103 patients) of unselected clinical pituitary adenoma samples. From total RNA of frozen tumor samples (all subtypes) cDNA ( COMPLEMENTARY DNA) was synthesized and transcripts of PTTG, bFGF, IGF-1 were measured by Real-Time-PCR. Not only mRNA ( MESSENGER RNA) levels of bFGF, but also of IGF-1, correlated strongly with PTTG transcripts. This result was obtained, when all pituitary adenoma samples were included in the statistical calculations, irrespective of their subclassification. Our study suggests a connection between PTTG and IGF-1 in pituitary adenomas.

Familial early-onset dementia with complex neuropathological phenotype and genomic background

Neurobiology of Aging, 2016

Despite significant progress in our understanding of hereditary neurodegenerative diseases, the l... more Despite significant progress in our understanding of hereditary neurodegenerative diseases, the list of genes associated with early-onset dementia is not yet complete. In the present study, we describe a familial neurodegenerative disorder characterized clinically as the behavioral and/or dysexecutive variant of Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease with neuroradiologic features of Alzheimer&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s disease, however, lacking amyloid-β deposits in the brain. Instead, we observed a complex, 4 repeat predominant, tauopathy, together with a TAR DNA-binding protein of 43 kDa proteinopathy. Whole-exome sequencing on 2 affected siblings and 1 unaffected aunt uncovered a large number of candidate genes, including LRRK2 and SYNE2. In addition, DDI1, KRBA1, and TOR1A genes possessed novel stop-gain mutations only in the patients. Pathway, gene ontology, and network interaction analysis indicated the involvement of pathways related to neurodegeneration but revealed novel aspects also. This condition does not fit into any well-characterized category of neurodegenerative disorders. Exome sequencing did not disclose a single disease-specific gene mutation suggesting that a set of genes working together in different pathways may contribute to the etiology of the complex phenotype.

Paraneoplastic necrotizing myelopathy with hypertrophy of the cauda equina

Journal of Neurology, Dec 1, 2003

Localization of neuregulin-1α (heregulin-α) and one of its receptors, ErbB-4 tyrosine kinase, in developing and adult human brain

Brain Research Bulletin, May 15, 2006

... The double immunolabeling procedure for ErbB-4 and NRG-1α involved the use of the nickel-enha... more ... The double immunolabeling procedure for ErbB-4 and NRG-1α involved the use of the nickel-enhanced avidin–biotin technique to localize ErbB-4, followed by the application of Sternberger's unlabeled immunoenzyme (PAP) technique with 3,3′-diaminobenzidine as the ...

Mutationsanalyse im Promotor des "human pituitary tumor transforming gene 1 (hPTTG-1)" in Hypophysenadenomen /

ABSTRACT

Pathologic estimation of oral mucosa lesions in actinomyces infection and the critical role of HSP and CD43 (A morphological and immunohistochemical study)

Periodontal disease is infection affecting the gums and bone supporting the teeth and is caused b... more Periodontal disease is infection affecting the gums and bone supporting the teeth and is caused by bacteria that accumulate in dental plaque due to infrequent or ineffective oral hygiene. The present study summarizes the pathological alterations related to this condition and examines further the expression of HSP70, CD43 and CD68 on the surface of epithelial cells, inflammatory cells and actinomyces in the oral mucosa of disabled patients with clinical manifestation of the disease. Forty two oral mucosa tissue specimens infected by actinomyces were examined in archival paraffin embedded tissue blocks. Ten healthy control specimens were also investigated. All specimens were evaluated for the expression of HSP70, CD68 and CD43. A standard three-step immunoperoxidase staining method was used. The inflammatory reaction consisted mainly of lymphocytes and plasma cells. HSP70 was overexpressed in inflammatory cells as well as on actinomyces’ surface and basal cells of the epithelium with ...