scholarly journals Therapeutic pathomorphosis in malignant glioma tissues after photodynamic therapy with сhlorin e6 (reports of two clinical cases)

2020 ◽  
Vol 9 (2) ◽  
pp. 45-54
Author(s):  
A. Yu. Rynda ◽  
D. M. Rostovtsev ◽  
V. E. Olyushin ◽  
Yu. M. Zabrodskaya
Keyword(s):  
Photodynamic Therapy ◽  
Malignant Glioma ◽  
Immunohistochemical Analysis ◽  
Malignant Neoplasms ◽  
Glial Tumor ◽  
Ki 67 ◽  
Tissue Samples ◽  
Malignant Glioma Cells ◽  
Cell Proliferation Marker

In recent years, photodynamic therapy (PDT) has been increasingly introduced into the surgical practice of treating malignant neoplasms. In this publication, the authors show the appearance of therapeutic pathomorphosis in vivo in human malignant glioma cells after intraoperative photodynamic therapy. Tissue samples obtained 10–14 days after PDT revealed nuclear and cytoplasmic signs indicating apoptosis, necrosis, and autophagy. A decrease in the proliferative activity of glial tumor cells and their higher death count were detected.. Immunohistochemical analysis shows decreases expression of Ki-67 cell proliferation marker and decreased amount of transcription factor protein p53.

scholarly journals Increasing the efficiency of hyperthermic intraperitoneal chemotherapy (HIPEC) by a combination with a photosensitive drug in pediatric rhabdomyosarcoma

2021 ◽  
Author(s):  
Benedikt Wagner ◽  
Anna Adamus ◽  
Laura Hempfling ◽  
Reza Vahdad ◽  
Antje Haap-Hoff ◽  
...  
Keyword(s):  
Animal Model ◽  
Photodynamic Therapy ◽  
Intraperitoneal Chemotherapy ◽  
Hyperthermic Intraperitoneal Chemotherapy ◽  
Ki 67 ◽  
Tissue Samples ◽  
Proliferation Capacity ◽  
Tumor Dissemination ◽  
Cell Layers

Background: Cytoreductive surgery (CRS) in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is an option in advanced peritoneal sarcomatosis. Nevertheless, CRS and HIPEC are not successful in all patients. An enhancement of HIPEC using photodynamic therapy might be beneficial. Therefore, a combination of the photosensitizer Hypericin (HYP) with HIPEC was evaluated in an animal model. Procedure: An established HIPEC animal model for rhabdomyosarcoma (NOD/LtSz-scid IL2Rγnullmice, n=80) was used. All groups received HYP (100 µg/200 µl) intraperitoneally with and without cisplatin-based (30 or 60 mg/m2) HIPEC (37 or 42 °C, for 60 min) (five groups, each n=16). Tumor dissemination was documented visually and by using HYP-based fluorescence guidance. HYP-based photodynamic therapy (PDT) of the tumor was performed. Finally, tissue samples were evaluated regarding proliferation (Ki-67) and apoptosis (TUNEL). Results: HYP uptake even in smallest tumor nodes (< 1 mm) was found. HYP-based fluorescence guidance allowed a better tumor detection in comparison to visual inspection. Immunohistochemistry revealed HYP penetration across the tumor surface. HYP-based PDT without HIPEC induced marginal apoptotic effects at the tumor surface. Combining HYP with HIPEC revealed cisplatin concentration dependent decrease in proliferation capacity and induction of apoptosis across determined cell layers of the tumor surfaces. Conclusion: HYP as fluorescent photosensitizer offers an intraoperative diagnostic advantage detecting intraperitoneal tumor dissemination. The combination of HYP and cisplatin-based HIPEC was feasible in vivo showing enhanced effects on tumor proliferation and apoptosis induction across the tumor surface. Further studies combining HYP and HIPEC will follow to establish a clinical application.

scholarly journals Splicing factor SRSF1 promotes breast cancer progression via oncogenic splice switching of PTPMT1

2021 ◽  
Vol 40 (1) ◽  
Author(s):  
Jun-Xian Du ◽  
Yi-Hong Luo ◽  
Si-Jia Zhang ◽  
Biao Wang ◽  
Cong Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
High Risk Group ◽  
Clinical Samples ◽  
Binding Motif ◽  
Ki 67 ◽  
Tissue Samples

Abstract Background Intensive evidence has highlighted the effect of aberrant alternative splicing (AS) events on cancer progression when triggered by dysregulation of the SR protein family. Nonetheless, the underlying mechanism in breast cancer (BRCA) remains elusive. Here we sought to explore the molecular function of SRSF1 and identify the key AS events regulated by SRSF1 in BRCA. Methods We conducted a comprehensive analysis of the expression and clinical correlation of SRSF1 in BRCA based on the TCGA dataset, Metabric database and clinical tissue samples. Functional analysis of SRSF1 in BRCA was conducted in vitro and in vivo. SRSF1-mediated AS events and their binding motifs were identified by RNA-seq, RNA immunoprecipitation-PCR (RIP-PCR) and in vivo crosslinking followed by immunoprecipitation (CLIP), which was further validated by the minigene reporter assay. PTPMT1 exon 3 (E3) AS was identified to partially mediate the oncogenic role of SRSF1 by the P-AKT/C-MYC axis. Finally, the expression and clinical significance of these AS events were validated in clinical samples and using the TCGA database. Results SRSF1 expression was consistently upregulated in BRCA samples, positively associated with tumor grade and the Ki-67 index, and correlated with poor prognosis in a hormone receptor-positive (HR+) cohort, which facilitated proliferation, cell migration and inhibited apoptosis in vitro and in vivo. We identified SRSF1-mediated AS events and discovered the SRSF1 binding motif in the regulation of splice switching of PTPMT1. Furthermore, PTPMT1 splice switching was regulated by SRSF1 by binding directly to its motif in E3 which partially mediated the oncogenic role of SRSF1 by the AKT/C-MYC axis. Additionally, PTPMT1 splice switching was validated in tissue samples of BRCA patients and using the TCGA database. The high-risk group, identified by AS of PTPMT1 and expression of SRSF1, possessed poorer prognosis in the stage I/II TCGA BRCA cohort. Conclusions SRSF1 exerts oncogenic roles in BRCA partially by regulating the AS of PTPMT1, which could be a therapeutic target candidate in BRCA and a prognostic factor in HR+ BRCA patient.

scholarly journals ATPS-42INHIBITION OF STAT3 ENHANCES THE RADIOSENSITIZING EFFECT OF TEMOZOLOMIDE IN MALIGNANT GLIOMA CELLS IN VITRO AND IN VIVO

2015 ◽  
Vol 17 (suppl 5) ◽  
pp. v27.3-v27
Author(s):  
Tae Jin Han ◽  
Eun Jung Choi ◽  
Bong Jun Cho ◽  
Sang Hyuk Song ◽  
Sun Ha Paik ◽  
...  
Keyword(s):  
Malignant Glioma ◽  
Glioma Cells ◽  
Radiosensitizing Effect ◽  
Malignant Glioma Cells

scholarly journals Exploring the activity of a polyazine bridged Ru(ii)–Pt(ii) supramolecule in F98 rat malignant glioma cells

2017 ◽  
Vol 53 (1) ◽  
pp. 145-148 ◽  
Author(s):  
Jie Zhu ◽  
José Á. Rodríguez-Corrales ◽  
Reece Prussin ◽  
Zongmin Zhao ◽  
Anthony Dominijanni ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Malignant Glioma ◽  
Glioma Cells ◽  
Target Dna ◽  
Malignant Glioma Cells

[(Ph2phen)2Ru(dpp)PtCl2]Cl2exhibits multiple light-dependent cytotoxicity pathways that preferentially target DNA, offering promise for the development of novel photodynamic therapy agents.

scholarly journals Niraparib Suppresses Cholangiocarcinoma Tumor Growth by Inducing Oxidative and Replication Stress

Cancers ◽  
2021 ◽  
Vol 13 (17) ◽  
pp. 4405
Author(s):  
Vladimir Bezrookove ◽  
John M. Patino ◽  
Mehdi Nosrati ◽  
Pierre-Yves Desprez ◽  
Sean McAllister ◽  
...  
Keyword(s):  
Dna Damage ◽  
Tumor Growth ◽  
The Cancer Genome Atlas ◽  
Genomic Alteration ◽  
M Cell ◽  
Ki 67 ◽  
Tissue Samples ◽  
Patient Derived Xenograft ◽  
Fork Stalling

Cholangiocarcinoma (CCA) is the second most common hepatobiliary cancer, an aggressive malignancy with limited therapeutic options. PARP (poly (ADP-ribose) polymerase) 1 and 2 are important for deoxyribonucleotide acid (DNA) repair and maintenance of genomic stability. PARP inhibitors (PARPi) such as niraparib have been approved for different malignancies with genomic alteration in germline BRCA and DNA damage response (DDR) pathway genes. Genomic alterations were analyzed in DDR genes in CCA samples employing The Cancer Genome Atlas (TCGA) database. Mutations were observed in various DDR genes, and 35.8% cases had alterations in at least one of three genes (ARID1A, BAP1 and ATM), suggesting their susceptibility to PARPi. Niraparib treatment suppressed cancer cell viability and survival, and also caused G2/M cell cycle arrest in patient-derived xenograft cells lines (PDXC) and established CCA cells harboring DDR gene mutations. PARPi treatment also induced apoptosis and caspase3/7 activity in PDXC and CCA cell lines, and substantially reduced expression of BCL2, BCL-XL and MCL1 proteins. Niraparib caused a significant increase in oxidative stress, and induced activation of DNA damage markers, phosphorylation of CHK2 and replication fork stalling. Importantly, niraparib, in combination with gemcitabine, produced sustained and robust inhibition of tumor growth in vivo in a patient-derived xenograft (PDX) model more effectively than either treatment alone. Furthermore, tissue samples from mice treated with niraparib and gemcitabine display significantly lower expression levels of pHH3 and Ki-67, which are a mitotic and proliferative marker, respectively. Taken together, our results indicate niraparib as a novel therapeutic agent alone or in combination with gemcitabine for CCA.

Arginine deiminase: A novel radiosensitizer in pancreatic cancer in vitro and in vivo.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 221-221 ◽  
Author(s):  
Amit Deorukhkar ◽  
Nga Diep ◽  
Dev Chatterjee ◽  
Parmeswaran Diagaradjane ◽  
John S. Bomalaski ◽  
...  
Keyword(s):  
Pancreatic Cancer ◽  
Immunohistochemical Analysis ◽  
Arginine Deiminase ◽  
Single Amino Acid ◽  
Ki 67 ◽  
Tumor Doubling Time ◽  
Tumor Tissues ◽  
Promising Therapeutic Approach

221 Background: The benefits of chemoradiation therapy in patients with locally advanced pancreatic cancer (LAPC) are limited due to the inherent radioresistance of pancreatic cancer (PC) and high systemic toxicity of current radiosensitizers (e.g., gemcitabine). Hence, the search for newer radiosensitizers with unique anticancer properties continues. Single amino acid arginine starvation is a new promising therapeutic approach for solid tumors (e.g., PC), that are auxotrophic for non-essential amino acids. Arginine degrading enzyme, arginine deiminase (ADI), deprives cells of arginine and thereby exerts its anti-proliferative effects, especially in cancer cells deficient in enzyme argininosuccinate synthase (ASS1). Here we evaluate the effects of ADI-polyethylene glycol formulation (ADI-PEG20) as a radiosensitizer in PC. Methods: The toxicity of ADI-PEG20 in vitro was evaluated using XTT. Effect of ADI-PEG20 as radiosensitizer was determined by clonogenic cell survival. For in vivo, mice with PC tumor xenografts (Panc1), randomized into four groups, were treated with vehicle (PBS), ADI-PEG20 (5 IU/mouse; twice weekly), radiation (IR; 2 Gy × 5 times), and ADI-PEG20 with IR. Tumors were measured following treatment and the tumor re-growth delay time for each group was calculated. Immunohistochemical analysis of Ki-67 and VEGF was done on tumor tissues (paraffin sections) by routine immunofluorescence. Results: ADI-PEG20 selectively sensitized ASS1 deficient PC cells to IR at low, non-toxic concentrations (0.04 and 0.08 μg/mL for 72 h; DER at 10% SF for Panc1 was 1.39 and 1.52; for Miapaca-2, 1.09 and 1.25 respectively), but not ASS1 positive cells (L3.6pl). In vivo, ADI-PEG20 profoundly sensitized PC cells to IR. IR treatment alone delayed the tumor doubling time (7.6 ± 1.7 days compared to the non-treated controls); however, combining ADI-PEG20 with IR delayed the tumor growth by an additional 10 ± 1.3 days (p<0.05). Immunohistochemical analysis of tumor tissues suggested that ADI-PEG20 with IR down-regulates the expression of Ki-67 and VEGF. Conclusions: ADI-PEG20 potently radiosensitizes PC cells in vitro and in vivo. The detailed molecular mechanism of this radiosensitization warrants further investigations.

scholarly journals Association of Ki-67 Labelling Index and IL-17A with Pituitary Adenoma

2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Brigita Glebauskiene ◽  
Rasa Liutkeviciene ◽  
Alvita Vilkeviciute ◽  
Inga Gudinaviciene ◽  
Aurelija Rocyte ◽  
...  
Keyword(s):  
Pituitary Adenoma ◽  
Pituitary Adenomas ◽  
Immunohistochemical Analysis ◽  
Serum Levels ◽  
Labelling Index ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Ki 67 ◽  
Tissue Samples ◽  
Median Serum

The aim of the present study was to determine if the Ki-67 labelling index reflects invasiveness of pituitary adenoma and to evaluate IL-17A concentration in blood serum of pituitary adenoma patients. The study was conducted in the Hospital of Lithuanian University of Health Sciences. All pituitary adenomas were analysed based on magnetic resonance imaging findings. The suprasellar extension and sphenoid sinus invasion by pituitary adenoma were classified according to Hardy classification modified by Wilson. Knosp classification system was used to quantify the invasion of the cavernous sinus. The Ki-67 labelling index was obtained by immunohistochemical analysis with the monoclonal antibody, and serum levels of IL-17A were determined by enzyme-linked immunosorbent assay (ELISA). Sixty-nine PA tissue samples were investigated. Serum levels of IL–17A were determined in 60 patients with PA and 64 control subjects. Analysis revealed statistically significantly higher Ki-67 labelling index in invasive compared to noninvasive pituitary adenomas. Median serum IL-17A level was higher in the pituitary adenoma patients than in the control group. Conclusion. IL-17A might be a significant marker for patients with pituitary adenoma and Ki-67 labelling index in case of invasive pituitary adenomas.

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