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Keywords: optical coherence tomography, angiography, endoscopy, oncology, skin carcinoma
Published in DiRROS: 26.07.2024; Views: 16; Downloads: 5
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Abstract: Background. Electrochemotherapy has good local effectiveness in the treatment of vulvar cancer. Most studies have reported the safety and effectiveness of electrochemotherapy for palliative treatment of gynecological cancers and mostly vulvar squamous cell carcinoma. Some tumors, however, fail to respond to electrochemotherapy. The biological features/determinants for the nonresponsiveness are not determined yet. Patient and methods. A recurrence of vulvar squamous cell carcinoma was treated by electrochemotherapy using intravenous administration of bleomycin. The treatment was performed by hexagonal electrodes according to standard operating procedures. We analyzed the factors that could determine nonresponsiveness to electrochemotherapy. Results. Based on the presented case of nonresponsive vulvar recurrence to electrochemotherapy, we hypothesize that the vasculature of the tumors prior to treatment may predict the response to electrochemotherapy. The histological analysis showed minimal presence of blood vessels in the tumor. Thus, low perfusion may reduce drug delivery and lead to a lower response rate because of the minor antitumor effectiveness of vascular disruption. In this case, no immune response in the tumor was elicited by electrochemotherapy. Conclusions. In this case, of nonresponsive vulvar recurrence treated by electrochemotherapy, we analyzed possible factors that could predict treatment failure. Based on histological analysis, low vascularization of the tumor was observed, which hampered drug delivery and distribution and resulted in no vascular disrupting action of electrochemotherapy. All these factors could contribute to ineffective treatment with electrochemotherapy.
Keywords: electrochemotherapy, bleomycin, vulvar cancer
Published in DiRROS: 25.07.2024; Views: 17; Downloads: 6
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Abstract: Immune therapies are currently under intensive investigation providing in many cases excellent re-sponses in different tumors. Other possible approach for immunotherapy is a targeted intratumoral delivery of inter-leukin 12 (IL-12), a cytokine with anti-tumor effectiveness. Due to its immunomodulatory action, it can be used as an imunostimulating component to in situ vaccinating effect of local ablative therapies. We have developed a phIL12 plasmid devoid of antibiotic resistance marker with a transgene for human IL-12 p70 protein. The plasmid can be delivered intratumorally by gene electrotransfer (GET). Patients and methods. Here we present a first-in-human clinical trial protocol for phIL12 GET (ISRCTN15479959, ClinicalTrials NCT05077033). The study is aimed at evaluating the safety and tolerability of phIL12 GET in treatment of basal cell carcinomas in patients with operable tumors in the head and neck region. The study is designed as an ex-ploratory, dose escalating study with the aim to determine the safety and tolerability of the treatment and to identify the dose of plasmid phIL12 that is safe and elicits its biological activity. Conclusions. The results of this trail protocol will therefore provide the basis for the use of phIL12 GET as an adjuvant treatment to local ablative therapies, to potentially increase their local and elicit a systemic response.
Keywords: skin tumors, gene electrotransfer, interleukin 12, clinical trial
Published in DiRROS: 24.07.2024; Views: 15; Downloads: 2
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Abstract: Background: Increased radioresistance due to previous irradiation or radiosensitivity due to human papilloma virus (HPV) infection can be observed in head and neck squamous cell carcinoma (HNSCC). The DNA-damage response of cells after exposure to DNA-damaging agents plays a crucial role in determining the fate of exposed cells. Tightly regulated and interconnected signaling networks are activated to detect, signal the presence of and repair the DNA damage. Novel therapies targeting the DNA-damage response are emerging; however, an improved understanding of the complex signaling networks involved in tumor radioresistance and radiosensitivity is needed. Materials and methods: In this study, we exposed isogenic human HNSCC cell lines with altered radiosensitivity to DNA-damaging agents: radiation, cisplatin and bleomycin. We investigated transcriptional alterations in the DNA-damage response by using a pathway-focused panel and reverse-transcription quantitative PCR. Results: In general, the isogenic cell lines with altered radiosensitivity significantly differed from one another in the expression of genes involved in the DNA-damage response. The radiosensitive (HPV-positive) cells showed overall decreases in the expression levels of the studied genes. In parental cells, upregulation of DNA-damage signaling and repair genes was observed following exposure to DNA-damaging agents, especially radiation. In contrast, radioresistant cells exhibited a distinct pattern of gene downregulation after exposure to cisplatin, whereas the levels in parental cells were unchanged. Exposure of radioresistant cells to bleomycin did not significantly affect the expression of DNA-damage signaling and repair genes. Conclusions: Our analysis identified several possible targets: NBN, XRCC3, ATR, GADD45A and XPA. These putative targets should be studied and potentially exploited for sensibilization to ionizing radiation and/or cisplatin in HNSCC. The use of predesigned panels of DNA-damage signaling and repair genes proved to offer a convenient and quick approach to identify possible therapeutic targets.
Keywords: DNA-damaging agents, gene expression, head and neck cancer, squamous cell carcinoma
Published in DiRROS: 24.07.2024; Views: 16; Downloads: 5
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Abstract: Background. Electrochemotherapy is an effective treatment of colorectal liver metastases and hepatocellular carcinoma (HCC) during open surgery. The minimally invasive percutaneous approach of electrochemotherapy has already been performed but not on HCC. The aim of this study was to demonstrate the feasibility, safety and effectiveness of electrochemotherapy with percutaneous approach on HCC. Patient and methods. The patient had undergone the transarterial chemoembolization and microwave ablation of multifocal HCC in segments III, V and VI. In follow-up a new lesion was identified in segment III, and recognized by multidisciplinary team to be suitable for minimally invasive percutaneous electrochemotherapy. The treatment was performed with long needle electrodes inserted by the aid of image guidance. Results. The insertion of electrodes was feasible, and the treatment proved safe and effective, as demonstrated by control magnetic resonance imaging. Conclusions. Minimally invasive, image guided percutaneous electrochemotherapy is feasible, safe and effective in treatment of HCC.
Keywords: electrochemotherapy, hepatocellular carcinoma, percutaneous, minimally invasive
Published in DiRROS: 12.07.2024; Views: 98; Downloads: 19
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