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At least 19 recordsLinked to original sources

Biomaterial-Integrated Electroporation for Therapeutic Delivery: From Gene Editing to Tumor Ablation and Immune Modulation.

Electroporation has evolved from a membrane-permeabilization method into a versatile therapeutic platform for intracellular delivery, locoregional tumor intervention, and bioelectrically regulated treatment. Depending on pulse intensity and duration, electroporation operates in two distinct modes: reversible electroporation (RE), which transiently permeabilizes the plasma membrane to enable delivery of nucleic acids, proteins, and small molecules while preserving cell viability, and irreversible electroporation (IRE), which causes permanent membrane damage for non-thermal tissue ablation. Increasingly, the therapeutic scope of electroporation is being expanded through integration with biomaterials, including nanocarriers, hydrogels, soft conductors, and micro/nanoengineered bioelectronic interfaces. These material-assisted strategies improve cargo protection, field confinement, local retention, tissue conformity, and spatiotemporal control, thereby extending electroporation beyond conventional transfection toward gene editing, engineered cell manufacturing, electrochemotherapy, tumor ablation, immune modulation, and transdermal or localized delivery. In this Review, we summarize the biophysical principles of RE and IRE, discuss how biomaterials reshape electroporation performance across therapeutic settings, compare the design logic of major biomaterial-assisted electroporation platforms, and highlight key translational challenges, including pulse-material compatibility, manufacturing scalability, in vivo dosimetry, and regulatory complexity.

Humans

High-Frequency Irreversible Electroporation Alters Proteomic Profiles and Tropism of Small Tumor-Derived Extracellular Vesicles to Promote Immune Cell Infiltration.

High-frequency irreversible electroporation (H-FIRE) is a nonthermal tumor ablation technique that disrupts the blood-brain barrier (BBB) in a focal and reversible manner. However, the mechanisms underlying this disruption remain poorly understood, particularly the role of small tumor-derived extracellular vesicles (sTDEVs) released from ablated tumor cells. In this study, we investigate the proteomic and functional alterations of sTDEVs released from F98 glioma and LL/2 Lewis lung carcinoma cells following H-FIRE ablation. Mass spectrometry analysis revealed 108 unique proteins in sTDEVs derived from ablative doses of H-FIRE, which are capable of disrupting the BBB in an in vitro model. Proteomic analysis of TDEVs highlights key changes in pathways related to integrin signaling, Platelet-derived growth factor receptor (PDGFR) signaling, and ubiquitination, which may underline their interactions with brain endothelial cells. These "disruptive" sTDEVs exhibit enhanced tropism for cerebral endothelial cells both in vitro and in vivo, where they persist in the brain longer than sTDEVs released after non-ablative H-FIRE doses. Notably, when introduced into a healthy Fischer rat model, disruptive sTDEVs are associated with increased recruitment of Iba1+ immune cells, suggesting a potential role in modulating post-ablation immune responses. However, despite their altered protein composition, these vesicles do not directly increase BBB permeability in vivo. This study is the first to demonstrate that electroporation-based tumor ablation significantly alters the composition and functionality of tumor-derived extracellular vesicles, potentially influencing the tumor microenvironment post-ablation. These findings have important implications for developing multimodal treatment strategies that combine H-FIRE with systemic therapies to enhance efficacy while managing the peritumoral microenvironment.

Animals

A photothermal ablation strategy for orthotopic ovarian cancer via mitochondria-dependent apoptosis.

Photothermal therapy (PTT) shows promise for ovarian cancer, but unclear cell death mechanisms slow its clinical use. Here, we report two-dimensional rhenium diselenide (ReSe₂) nanosheets as a stable, high-performance photothermal agent that triggers ovarian cancer cell apoptosis through a mitochondria-dependent pathway. Under near-infrared light, ReSe₂ generates local hyperthermia. This triggers a rapid burst of intracellular reactive oxygen species, collapses mitochondrial membrane potential, and shifts the balance between pro- and anti-apoptotic Bcl-2 family proteins. In an orthotopic mouse model, this defined apoptotic cascade strongly suppresses tumors with no detectable systemic toxicity. Our work not only elucidates a clear molecular mechanism for photothermal tumor ablation but also establishes ReSe₂-mediated PTT as a translatable therapeutic strategy, advancing the rational design of photothermal agents based on biological mechanism.

Apoptosis

Management of advanced and recurrent facial carcinoma.

I report five cases of advanced and recurrent facial carcinoma to illustrate the extent to which such disease can develop and yet be compatible with life. Radical treatment approaches are used so as to maximize the chances for tumor ablation and survival as well as for restoration of function and cosmetics.

Aged

Detection of metastatic thyroid carcinoma after the administration of a therapeutic dose of 131-iodine.

A patient with thyroid cancer is described whose metastases were detected only after the administration of a large therapeutic dose of 131 Iodine. This suggests that very high doses of 131 Iodine might permit diagnoses of metastatic lesions not otherwise detected. This phenomenon may be explained by the improved counting statistics which occur with the use of a higher dose of the isotope. In such cases, exceedingly high doses of 131 Iodine might be necessary for successful tumor ablation.

Female

Immediate facial rehabilitation in poor prognosis tumor patients.

Effective rehabilitation of facial paralysis in the poor prognosis tumor patient is best accomplished by the judicious and individualized use of that combination of static or static and dynamic procedures which will correct the major deformities present immediately and with minimal morbidity. This approach may be taken at the time of tumor ablation or later when the effects of paralysis become distressingly evident. In the rare patient whose disease is controlled, additonal dynamic rehabilitative efforts may be considered subsequently.

Aged

Prolactin receptors in 7,12-dimethylbenz(a) anthracene-induced mammary tumors following endocrine ablation.

We have determined the effect of ovariectomy and hypophysectomy on prolactin receptors in 7,12-dimethylbenz(a)anthracene-induced mammary tumors. Growing tumors from intact rats show a wide range in the number of prolactin receptors. Ovariectomy causes a slight (approximately 30%) decrease in receptors regardless of whether tumors regress or continue to grow, while the affinity of the receptor for prolactin remains unchanged. Hypophysectomy, which causes a prompt 10-fold decrease in prolactin receptors in rat liver, causes only a slight reduction in prolactin receptors in tumors from these same animals. We conclude that autonomous and ovariectomy responsive 7,12-dimethylbenz(a)anthracene-induced mammary tumors cannot be distinguished on the basis of prolactin receptor sites and that endocrine regulation of prolactin receptors is distinctly different in normal liver and neoplastic mammary tissue.

9,10-Dimethyl-1,2-benzanthracene

Estrogen and prolactin receptor concentrations in rat mammary tumors and response to endocrine ablation.

Estrogen and prolactin receptor concentrations were measured in 24 carcinogen-induced rat mammary tumors and correlated with the tumor response to host ovariectomy or hypophysectomy. It was found that essentially all of the tumors contained some specific estrogen receptor, and all but three contained prolactin receptor. The values for each receptor comprised a continuum from very low to relatively high concentrations, suggesting that previous considerations of hormone dependence on the basis of presence or absence of hormone receptors may be oversimplified. The concentration of each receptor tended to be lower in the hormone-independent than in the hormone-dependent tumors, but there were a number of hormone-independent tumors with higher receptor levels than some of the hormone-dependent tumors had. A better correlation of tumor response to endocrine ablation resulted from a combination of the 2 receptor levels than from either receptor concentration alone. These results suggest that there is a complex relationship between mammary tumor response to endocrine ablatin and levels of estrogen and prolactin receptors and that some tumors may be dependent upon 1 or both of these hormones for growth.

9,10-Dimethyl-1,2-benzanthracene

Engineered MXene-based nanozyme platform: NIR-II photothermal and dual enzyme-mimetic potentiated chemodynamic synergy for precision tumor eradication.

The antioxidant defense barrier in the tumor microenvironment, particularly glutathione (GSH), considerably restricts the therapeutic efficacy of chemodynamic therapy (CDT). Moreover, CDT generally exhibits relatively mild therapeutic efficacy owing to its intrinsic reaction kinetics, making it difficult to achieve complete tumor eradication within a short time. To address these issues, we construct a functionalized nanotherapeutic platform, Nb2CTx@Ru-PEG2000-FA (NCRPF), for tumor photothermal ablation and enhanced CDT resulting from GSH depletion. NCRPF possesses three key advantages: 1. Efficient near-infrared II photothermal conversion (η = 42.08%), raising the tumor temperature above 45 °C within 90 s for rapid ablation; 2. Dual peroxidase-like and glutathione peroxidase-like activities, simultaneously depleting GSH and generating a burst of ·OH to eliminate residual tumors; 3. Targeted tumor accumulation with 2.9-fold higher efficiency than passive diffusion. Both in vitro and in vivo results confirm that this combined strategy achieves complete tumor eradication with favorable biosafety. Collectively, the NCRPF nanotherapeutic system provides a powerful new paradigm with high translational potential for the complete eradication of breast cancer.

Animals

Detection of cancer-associated antigen(s) in urine of sarcoma patients.

Tumor-associated antigens were demonstrated in concentrated and dialyzed urine of several sarcoma patients with large tumor burden. The antigens were detected by complement fixation using autologous and allogeneic sera from sarcoma patients. The antigenic activity in three patients who were studied sequentially disappeared after surgical ablation of tumor. In two of these three patients, the antigenic activity reappeared before tumor recurrence. The reactivity of the sarcoma sera to the urine could be abolished by absorption of the sera with human sarcoma cells but not by normal human liver cells, which indicates that the same antigen was present in the urine and on biopsy-obtained sarcoma cells. Urine from cancer patients with high tumor burden may be useful as a source of tumor-associated antigen. Further studies on the presence of these antigens in urine of sarcoma patients may lead to a method for detecting subclinical tumor recurrence.

Adult

Possible retention of the estrogen-binding capacity after endocrine ablation therapy in the rat and human breast cancer.

The estrogen-binding capacity of the regrowing tumors after endocrine ablation surgery was estimated in the rat and human breast cancer. All of 4 tumors that had not had the estrogen receptor before oophorectomy did not show the estrogen-binding capacity after the procedure, in the mammary cancer in the Sprague-Dawley rat induced by 7,12-dimethylbenz[a]anthracene, whereas all the 4 tumors that had the receptor before the procedure showed the binding capacity after oophorectomy. In 4 patients who had been subjected to the major endocrine ablation therapy because of metastatic breast cancer with effective response, the secondary metastatic deposits of cancer showed the estrogen-binding capacity long after the endocrine ablation. The fact that regrowing tumors after complete or partial regression of initial tumors by endocrine ablation retain the estrogen receptor seems to be contradictory to the classical concept of autonomy in recurrence of the breast cancer after hormonal manipulation.

9,10-Dimethyl-1,2-benzanthracene

Ovarian sex cord tumor with annular tubules. Clinicopathologic report of two benign and one malignant cases with long follow-ups.

The clinicopathologic features of three new cases of ovarian sex cord tumors with annular tubules are presented, thereby increasing to 23 the number of the published cases in the world literature. These three observations, along with another one which was previously published, were found in the files of the Institute of Pathology of the University of Lausanne from 1939 to 1978. Forty-seven granulosa cell tumors and eight Sertoli and/or Leydig cell tumors of the ovary were found during the same 40-year period. The patients were 48, 64 and 71 years of age. No sign of the Peutz-Jeghers syndrome was noticed in the three patients. All three tumors caused metrorrhagias as a cardinal sign. They were bulky, unilateral and were formed by solid tissue with cystic spaces. Histologically, the most characteristic pattern consisted of simple and complex tubular structures as described by Scully in 1970. Two patients, in which the mitotic indexes of the tumors were lower than 5 mitoses per 10 HPF, died without evidence of a recurrence 36 and 37 years after surgical ablation of the tumor. The third patient, whose neoplasm featured fewer well differentiated tubular structures than the two previous ones and had a mitotic index of over 70 mitoses per 10 HPF, died from massive abdominal recurrence after 5 years and 5 months.

Aged

On the mechanism of prolactin and estrogen action in 7,12 dimethylbenz(A)anthracene-induced mammary carcinoma in the rat. II. In vivo tumor responses and estrogen receptor.

In order to test the in vivo effect of prolactin on estrogen receptor (ER) binding capacity in tumors induced by 7,12 dimethylbenz(a)anthrancene (DMBA-tumor), growth of the tumors from changes in prolactin and estrogen levels was compared retrospectively with cytoplasmic ER levels. It was demonstrated that some tumors required prolactin, some needed prolactin-estrogen during their growth period anda small number were not influenced by hormonal milieu. ER was present in hormonally dependent tumors but was low or absent in hormonaly-independent tumors. Deletion of hormones by endocrine ablation in the host rat resulted in tumor regression loss of ER. Replenishment of ER and subsequent tumor growth were accomplished by injection of prolactin or prolactin-estrogen in endocrine ablated rats but were not achieved in rats bearing tumors exposed to prolactin-nafoxidine. Our results demonstrate that both estrogen and prolactin were essential for growth of hormonally dependent DMBA-tumors. Tumor growth was also prevented when cytoplasmic ER was not replenished , indicating that ER may be an indispensable prerequisite for growth. Prolactin, independently of or cooperatively with estrogen, stimulated ER binding capacity. These results support the hypothesis that there may exist a prolactin regulatory mechanism of estrogen action at the tumor site. The interactions of estrogen and prolactin in situ in modulating hormonal receptor binding capacities may contribute to the overall stimulatory effect of these two hormones on DMBA-tumors.

9,10-Dimethyl-1,2-benzanthracene

Estrogen-prolactin dependency in 7,12-dimethylbenz(a)anthracene-induced tumors.

Hormonal influences on dimethylbenz(a)anthracene-induced tumor growth were investigated in detail by endocrine ablation and replacement of hormones. The majority of tumors regressed following ablation and most of them were reactivated by subsequent administrations of estrogen (0.1 to 5 mug) or prolactin (2 mg). Increasing numbers of tumors, however, were not stimulated by prolactin when administration was delayed, and a basal level of estradiol (0.01 mug) in addition to prolactin was required for reactivation of tumors. Nafoxidine hydrochloride, a competitor of estrogen at the receptor sites, arrested growth of a large portion of dimethylbenz(a)anthracene-induced tumors in intact animals but failed to retard growth of prolactin-stimulated tumors. On withdrawal of prolactin-nafoxidine, rapid regression of tumor occurred and readministration of prolactin failed to activate most of the tumors for as long as 28 days. Our results give good supporting evidence that estrogen plays a primary role in tumor growth. The interactions of prolactin and estrogen at tumor sites are necessary for regulatory events related to tumor growth.

Adenocarcinoma

Hemangiopericytoma. Literature review and clinical presentations.

Hemangiopericytomas are soft tissue sarcomas of vascular origin, comprised of pericytes. They have been reported in the extremities, head and neck, back, retroperitoneum, and abdomen. The criteria for the diagnosis and treatment are reviewed. Wide local ablation of the tumor is necessary to prevent local recurrence. Fifty per cent are malignant, although regional node spread is infrequent. Ultrastructural studies are necessary to differentiate hemangiopericytomas from other sarcomas. Long-term follow-up of all cases is essential for optimal clinical management.

Adult

Dermatofibrosarcoma protuberans.

Dermatofibrosarcoma protuberans is a well-differentiated sarcoma that rarely metastasizes but is characterized by a high recurrence rate. This is due to clinically undetectable, microscopic extensions into the surrounding dermis. Chemosurgery (Mohs) is effective in the ablation of this tumor because the extensions can be identified and eradicated.

Adult

The use of postoperative irradiation--its goals and 1978 attainments.

The use of postoperative irradiation as an adjunctive measure for better control of local and regional disease after a surgical procedure has been used at the Anderson Hospital since approximately 1965. The common clinical setting occurs in those patients in whom, after surgical ablation of the tumor, there are microscopic foci of residual disease at the margins, perineural invasion, histologically a very poorly differentiated carcinoma, dermal lymphatic involvement, multiple nodes in the neck or very large nodes in which the tumor has broken through the nodal capsule and entered the connective tissue. We have been applying this criterion for the treatment of salivary gland malignancies, squamous carcinomas of the hypopharynx and supraglottic larynx, and all sites in the head and neck in which there was extensive cercical nodal metastasis. The results of this therapeutic approach will be reported and discussed.

Carcinoma, Squamous Cell