Cetuximab-Taxanes-Platinum-Fluorouracil/Capecitabine (C-TPF/C-TPX) – a Feasible Option for Recurrent HNSCC with Negative Prognostic Factors. Literature Review with a Case Presentation

Concurrent chemo-radiotherapy with Cisplatin is the standard treatment for locally advanced non-metastatic squamous cell carcinoma of the head and neck (HNSCC), but induction chemotherapy (IC) followed by chemo-irradiation, even controversial is a widely accepted option, especially in high-risk cases. A regimen including triple association (platinum-taxanes-fluorouracil) is generally considered superior in efficacy, but may be associated with severe toxicity. In the case of recurrence, the options are limited and the prognosis is generally unfavorable. Chemotherapy alone or in combination with an anti-EGFR monoclonal antibody (Cetuximab), immunotherapy or re-irradiation for selected cases are feasible options in loco-regional or metastatic relapse. We present a case of nasopharyngeal cancer (NPC), with negative prognostic and predictive factors multimodally treated with an intensive chemotherapy regimen associating Cetuximab with a median survival higher than the median value reported in most studies. Replacing 5 Floururacil with Capecitabine and Cisplatin with Carboplatin may be an option to increase treatment tolerance and should be evaluated in randomized trials. The use of induction chemotherapy as a “new standard” before radio-chemotherapy for cases with negative prognostic factors should also be the subject of future studies. Re-challenge with platinum is also an option that needs to be re-evaluated

COLD ATMOSPHERIC PLASMA TREATMENT MODULATES THE EXPRESSION OF cdk1, tnfα AND tp53 GENES IN HUMAN OSTEOSARCOMA CELLS

Osteosarcoma (OS), a malignancy primarily affecting children and adolescents, is the most frequently encountered malignant, non-hematologic, bone tumor. Despite the gradual improvement of survival rates, the management of this disease remains problematic due to challenges such metastasis development, its heterogeneous characteristics, and resistance to cytostatic drugs. Cold atmospheric plasma (CAP), a partially ionized gas operating at near room temperature, which is comprised of free carriers, excited or neutral molecules, and active radicals capable of initiating diverse physical phenomena and chemical reactions represent a new and innovative potential solution in cancer therapy. The aim of this study was to evaluate the capacity of CAP produced by our custom-build plasma source to induce cytotoxic effects to HOS cells and to analyze post-treatment modulations of cdk1, tnfα and tp53 genes expression. Direct and indirect CAP treatments effectiveness on HOS cells were evaluated by MTT assay and the regulation of interest genes expression were carried out by RT-qPCR analysis. Cell viability analysis revealed a strong cytotoxic effect of direct CAP treatment on HOS cells, while the indirect treatment resulted in a slight decrease of cells viability. Direct CAP treatment modulates the expression of all analyzed genes, both at 2- and 24-hours post-treatment. In conclusion, direct CAP treatment produced by our custom-build plasma source have cytotoxic effects on HOS cells in a dose-dependent manner up to 24 hours post-treatment. Furthermore, direct CAP treatment induces cell cycle arrest of HOS cells, and the CAP-induced cell death is independent of tp53 gene

Skin Cancers of the Head and Neck Region: the Real World Epidemiological and Therapeutic Data from the Cancer Registry of Dolj County

The majority of skin cancers of the head and neck are represented by basal cell carcinoma (BCC) and cutaneous squamosal cell carcinoma (CSCC), both non-melanoma skin cancers. Identified in the early stages, the cure rate is considered high. Sun protection and early identification of suspicious lesions are the optimal strategies for these cancers to be associated with higher response rates and favorable cosmetic results. Even if the incidence is lower, 10% to 25% of melanomas could also be identified in the head and neck region. For advanced stages or for cases ineligible for optimal surgical treatment, the multimodal approach including adjuvant radiotherapy, chemotherapy, biological therapy or immunotherapy must be decided in a multidisciplinary team. We set out to retrospectively evaluate the data of patients with skin tumors in the head and neck region included in the cancer registry of Dolj county between January 2000 and December 2019. Seventy-three patients were subsequently identified who met the inclusion criteria. The median age of the patients was 73 years (46 to 98). Forty-six cases of these were BCC, 15 CSCC cases, 1 adenoid cystic carcinoma case, 1 malignant melanoma case and one case without histopathological confirmation. The ratio between BCC and CSCC in our study is 3:1, in concordance with the ratio identified in the literature. The vast majority of cases come from the urban environment, surgery being the main treatment, especially for the early stages. Adjuvant radiotherapy was administered both in cases of BCC and epidermoid carcinoma. Adjuvant polychemotherapy, interferon therapy and re-irradiation have also been used. Considering the main risk factor, exposure to the sun, it is possible that the predominance of cases from cities is caused by underreporting of these types of cancer in rural communities where the main occupation is agriculture, associated with sun exposure, but also by a lower addressability or non-compliance with the inclusion in the oncological monitoring programs. The current existence of some modern oncological therapies, including immunotherapy for CSS and malignant melanoma, justifies a better monitoring and inclusion of these cases in multidisciplinary evaluation. Superficial radiotherapy, which has now become less accessible in our country, due to the implementation of radiological safety rules and the conversion of equipment from the former Soviet Union cobalt and superficial X-ray radiotherapy device to modern liniac accelerators focused on modern techniques radiotherapy is necessary to reduce the risk of recurrence in the case of resection with inadequate margins of non-melanoma skin tumors

Cold Atmospheric Plasma, Platelet-Rich Plasma, and Nitric Oxide Synthesis Inhibitor: Effects Investigation on an Experimental Model on Rats

The evolution of reconstructive methods for defects of the human body cannot yet replace the use of flap surgery. Research is still preoccupied with the ideal techniques for offering the best chances of survival of the flaps. In our study, we investigated the effects of cold atmospheric plasma (CAP), N-nitro-L-arginine methyl ester (L-NAME), and platelet-rich plasma (PRP) injectable solutions on flap survival using an in vivo model. Twenty-four Wistar rats (four groups) had the McFarlane flap raised and CAP, L-NAME, and PRP substances tested through a single dose subcutaneous injection. The control group had only a saline solution injected. To the best of our knowledge, this is the first study that evaluated a CAP activated solution through injection on flaps. The flap survival rate was determined by clinical examination (photography documented), hematology, thermography, and anatomopathological tests. The image digital analysis performed on the flaps showed that the necrosis area (control—49.64%) was significantly lower for the groups with the three investigated solutions: CAP (14.47%), L-NAME (18.2%), and PRP (23.85%). Thermography exploration revealed less ischemia than the control group on the CAP, L-NAME, and PRP groups as well. Anatomopathological data noted the best degree of angiogenesis on the CAP group, with similar findings on the L-NAME and PRP treated flaps. The blood work did not indicate infection or a strong inflammatory process in any of the subjects. Overall, the study shows that the CAP activated solution has a similar (better) impact on the necrosis rate (compared with other solutions with known effects) when injected on the modified dorsal rat skin flap, and on top of that it can be obtained fast, in unlimited quantities, non-invasively, and through a standardized process

Assessing the Neurotoxicity of a Sub-Optimal Dose of Rotenone in Zebrafish (Danio rerio) and the Possible Neuroactive Potential of Valproic Acid, Combination of Levodopa and Carbidopa, and Lactic Acid Bacteria Strains

first_page settings Order Article Reprints Open AccessArticle Assessing the Neurotoxicity of a Sub-Optimal Dose of Rotenone in Zebrafish (Danio rerio) and the Possible Neuroactive Potential of Valproic Acid, Combination of Levodopa and Carbidopa, and Lactic Acid Bacteria Strains by Ovidiu-Dumitru Ilie 1,† [ORCID] , Raluca Duta 1, Ioana-Miruna Balmus 2,3, Alexandra Savuca 4 [ORCID] , Adriana Petrovici 5 [ORCID] , Ilinca-Bianca Nita 6, Lucian-Mihai Antoci 7, Roxana Jijie 8,† [ORCID] , Cosmin-Teodor Mihai 9 [ORCID] , Alin Ciobica 1,*, Mircea Nicoara 1,4 [ORCID] , Roxana Popescu 7,10 [ORCID] , Romeo Dobrin 11,* [ORCID] , Carmen Solcan 5,* [ORCID] , Anca Trifan 12,13 [ORCID] , Carol Stanciu 12,13 and Bogdan Doroftei 6 [ORCID] 1 Department of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University, Carol I Avenue, no 20A, 700505 Iasi, Romania 2 Department of Exact and Natural Sciences, Institute of Interdisciplinary Research, “Alexandru Ioan Cuza” University, Carol I Avenue, no 11, 700506 Iasi, Romania 3 Doctoral School of Biology, Faculty of Biology, “Alexandru Ioan Cuza” University, Carol I Avenue, 20A, 700506 Iasi, Romania 4 Doctoral School of Geosciences, Faculty of Geography-Geology, “Alexandru Ioan Cuza” University, Carol I Avenue, no 20A, 700505 Iasi, Romania 5 Department of Molecular Biology, Histology and Embryology, Faculty of Veterinary Medicine, University of Life Sciences “Ion Ionescu de la Brad”, Mihail Sadoveanu Street, no 3, 700490 Iasi, Romania 6 Faculty of Medicine, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, no 16, 700115 Iasi, Romania 7 Department of Medical Genetics, University of Medicine and Pharmacy “Grigore T. Popa”, University Street, no 16, 700115 Iasi, Romania 8 Research Center on Advanced Materials and Technologies, Department of Exact and Natural Sciences, Institute of Inderdisciplinary Research, “Alexandru Ioan Cuza” University, Carol I Avenue, no 11, 700506 Iasi, Romania 9 Advanced Research and Development Center for Experimental Medicine (CEMEX), University of Medicine and Pharmacy “Grigore T. Popa”, University Street, no 16, 700115 Iasi, Romania 10 Department of Medical Genetics, “Saint Mary” Emergency Children’s Hospital, Vasile Lupu Street, no 62, 700309 Iasi, Romania add Show full affiliation list * Authors to whom correspondence should be addressed. † These authors equally contributed to this work. Antioxidants 2022, 11(10), 2040; https://doi.org/10.3390/antiox11102040 Received: 2 September 2022 / Revised: 3 October 2022 / Accepted: 13 October 2022 / Published: 17 October 2022 (This article belongs to the Special Issue Oxidative Stress and Neuroinflammation in Neurological and Neurodegenerative Disorders) Download Browse Figures Review Reports Versions Notes Abstract Parkinson’s disease (PD) is an enigmatic neurodegenerative disorder that is currently the subject of extensive research approaches aiming at deepening the understanding of its etiopathophysiology. Recent data suggest that distinct compounds used either as anticonvulsants or agents usually used as dopaminergic agonists or supplements consisting of live active lactic acid bacteria strains might alleviate and improve PD-related phenotypes. This is why we aimed to elucidate how the administration of rotenone (ROT) disrupts homeostasis and the possible neuroactive potential of valproic acid (VPA), antiparkinsonian agents (levodopa and carbidopa – LEV+CARB), and a mixture of six Lactobacillus and three Bifidobacterium species (PROBIO) might re-establish the optimal internal parameters. ROT causes significant changes in the central nervous system (CNS), notably reduced neurogenesis and angiogenesis, by triggering apoptosis, reflected by the increased expression of PARKIN and PINK1 gene(s), low brain dopamine (DA) levels, and as opposed to LRRK2 and SNCA compared with healthy zebrafish. VPA, LEV/CARB, and PROBIO sustain neurogenesis and angiogenesis, manifesting a neuroprotective role in diminishing the effect of ROT in zebrafish. Interestingly, none of the tested compounds influenced oxidative stress (OS), as reflected by the level of malondialdehyde (MDA) level and superoxide dismutase (SOD) enzymatic activity revealed in non-ROT-exposed zebrafish. Overall, the selected concentrations were enough to trigger particular behavioral patterns as reflected by our parameters of interest (swimming distance (mm), velocity (mm/s), and freezing episodes (s)), but sequential testing is mandatory to decipher whether they exert an inhibitory role following ROT exposure. In this way, we further offer data into how ROT may trigger a PD-related phenotype and the possible beneficial role of VPA, LEV+CARB, and PROBIO in re-establishing homeostasis in Danio rerio

Cold Atmospheric Plasma-Activated Media Improve Paclitaxel Efficacy on Breast Cancer Cells in a Combined Treatment Model

The use of plasma-activated media (PAM), an alternative to direct delivery of cold atmospheric plasma to cancer cells, has recently gained interest in the plasma medicine field. Paclitaxel (PTX) is used as a chemotherapy of choice for various types of breast cancers, which is the leading cause of mortality in females due to cancer. In this study, we evaluated an alternative way to improve anti-cancerous efficiency of PTX by association with PAM, the ultimate achievement being a better outcome in killing tumoral cells at smaller doses of PTX. MCF-7 and MDA-MB-231 cell lines were used, and the outcome was measured by cell viability (MTT assay), the survival rate (clonogenic assay), apoptosis occurrence, and genotoxicity (COMET assay). Treatment consisted of the use of PAM in combination with under IC50 doses of PTX in short- and long-term models. The experimental data showed that PAM had the capacity to improve PTX’s cytotoxicity, as viability of the breast cancer cells dropped, an effect maintained in long-term experiments. A higher frequency of apoptotic, dead cells, and DNA fragmentation was registered in cells treated with the combined treatment as compared with those treated only with PT. Overall, PAM had the capacity to amplify the anti-cancerous effect of PTX

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EVALUATION OF THE cELF- EMF DELAYED EFFECTS ON DNA INTEGRITY OF THE NORMAL CELLS

The aim of this study was evaluation of the late effects of a 100 Hz and 5.6 mT electromagnetic field, applied continuously, on the DNA integrity of Vero cells assessed by alkaline COMET assay. Normal Vero cells were exposed to extremely low frequency electromagnetic fiel (100 Hz, 5.6 mT) for 45 minutes. The COMET assay was performed after 48 hours from the treatment. Exposed samples presented an increase of the number of cells with high damaged DNA as compared with non-exposed cells. Quantitative evaluation of the comet assay showed a significantly (<0.001) increase of the tail lengths, of the quantity of DNA in tail and of Olive tail moments, respectively. The analysis of the registered comet indices showed that extremely low frequency electromagnetic field of 100 Hz and 5.6 mT had a genotoxic impact on Vero cells

Borrowing the Features of Biopolymers for Emerging Wound Healing Dressings: A Review

Wound dressing design is a dynamic and rapidly growing field of the medical wound-care market worldwide. Advances in technology have resulted in the development of a wide range of wound dressings that treat different types of wounds by targeting the four phases of healing. The ideal wound dressing should perform rapid healing; preserve the body&rsquo;s water content; be oxygen permeable, non-adherent on the wound and hypoallergenic; and provide a barrier against external contaminants&mdash;at a reasonable cost and with minimal inconvenience to the patient. Therefore, choosing the best dressing should be based on what the wound needs and what the dressing does to achieve complete regeneration and restoration of the skin&rsquo;s structure and function. Biopolymers, such as alginate (ALG), chitosan (Cs), collagen (Col), hyaluronic acid (HA) and silk fibroin (SF), are extensively used in wound management due to their biocompatibility, biodegradability and similarity to macromolecules recognized by the human body. However, most of the formulations based on biopolymers still show various issues; thus, strategies to combine them with molecular biology approaches represent the future of wound healing. Therefore, this article provides an overview of biopolymers&rsquo; roles in wound physiology as a perspective on the development of a new generation of enhanced, naturally inspired, smart wound dressings based on blood products, stem cells and growth factors