Highly focalised thermotherapy using a ferrimagnetic cement in the treatment of a melanoma mouse model by low temperature hyperthermia

Portela, Ana; Vasconcelos, Mário; Fernandes, Maria Helena; García, Manuel Francisco Martínez; Silva, António; Gabriel, Joaquim; Gärtner, Fátima; Amorim, Irina; Cavalheiro, J.

doi:10.3109/02656736.2013.767478

Cited by 11 publications

(8 citation statements)

References 46 publications

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“…A prominent finding in our study was the activation of the apoptotic pathway as evidenced by an increased expression of cleaved caspase-3 in both hyperthermia-treated groups. These results are in accordance with our previous in vitro findings together with observations, by other groups, showing the involvement of caspase-3 in triggering the apoptotic response in a number of different therapeutic protocols combined with hyperthermia (45,46,48,51). In contrast, COX-2 was shown to be expressed in significantly lower levels in the tumors of both hyperthermia-treated groups, a finding also in agreement with earlier studies exhibiting an increased expression of COX-2 in metastatic melanoma lesions and cell lines while being undetected in lesions of primary stages (53).…”

Section: Discussionsupporting

confidence: 93%

“…Furthermore, we have shown a remarkably prominent inhibition of tumor volume and size between hyperthermic and control conditions which further supports the significance of hyperthermia's therapeutic potential. A large number of studies are also in agreement with our in vivo findings although their focus was primarily on determining the efficacy of various clinical therapeutic protocols in combination with hyperthermia (43)(44)(45)(46)(47)(48)(49)(50)(51)(52).…”

Section: Discussionsupporting

confidence: 80%

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Hyperthermia Suppresses Post - In Vitro Proliferation and Tumor Growth in Murine Malignant Melanoma and Colon Carcinoma

et al. 2019

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Background: Several studies have highlighted hyperthermia's ability to enhance the effectiveness of radiation and chemotherapy in various in vitro and in vivo cancer models. Materials and Methods: In vivo murine models of malignant melanoma and colon carcinoma were utilized for demonstrating hyperthermia's therapeutic effectiveness by examining levels of caspase 3, COX-2 and phospho-H2A.X (Ser139) as endpoints of apoptosis, proliferation and DNA damage respectively. Results: Hyperthermia induced in vitro cytotoxicity in malignant melanoma (B16-F10) and colon carcinoma (CT26) cell lines. In addition, it reduced post-in vitro proliferation and suppression of tumor growth by inducing the expression of caspase-3 and phospho-H2A.X (Ser139) while reducing the expression of COX-2 in both murine cancer models. Conclusion: Hyperthermia can exert therapeutic effectiveness against melanoma and colon carcinoma by inhibiting a number of critical cellular cascades including apoptosis, proliferation and DNA damage. One of the most aggressive and deadliest malignancies of all solid tumors is malignant melanoma (MM). Its incidence rates have been continuously rising worldwide while the disease accounts for the majority of skin cancer-related deaths (1-4). MM occurs from the accumulation of genetic and metabolic abnormalities of melanocytes as well as other contributing factors like numerous atypical nevi (i.e. benign proliferations of melanocytes), genetic predisposition and solar ultraviolet (UV) (5-7). In particular, evidence from various studies have linked exposure to UV radiation with the increased occurrence of the disease, due to the mutagenic properties of UVR, thus making it the leading risk factor (8-10). The majority of MM cases present an active BRAF mutation, with V 600E being the most common one accounting for 90% of cases. The activation of other oncogene pathways including RAS, c-KIT, NRAS, PI3K and PTEN as well as inactivation of tumor suppressors such as CDKN2A have been also associated with the development of the disease (11, 12). However, although there has been significant progress on understanding MM's biology, the disease's pathogenesis has yet to be well characterized. Although there is remarkable progress in developing more targeted therapeutic approaches there is still a great need to design more effective treatment strategies due to the poor responsiveness of MM to current therapeutic means (13-15). On the other hand, colorectal or colon carcinoma (CRC) is a tumor type originating from epithelial cells residing in the colon or rectum of the gastrointestinal tract (16, 17). CRC is the third most common type of cancer diagnosed globally while it is the fourth leading cause of cancer-related 2307 This article is freely accessible online.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 80%

Hyperthermia Suppresses Post - In Vitro Proliferation and Tumor Growth in Murine Malignant Melanoma and Colon Carcinoma

et al. 2019

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“…Data from various clinical studies have shown that hyperthermia enhances the effectiveness of therapeutic strategies like radiation and chemotherapy 11 – 14 . In the case of malignant melanoma, there is only a limited number of reports investigating into the induction of cell death as a response to hyperthermia 10 , 15 , 16 .…”

Section: Discussionmentioning

confidence: 99%

Hyperthermia induces therapeutic effectiveness and potentiates adjuvant therapy with non-targeted and targeted drugs in an in vitro model of human malignant melanoma

Mantso

Vasileiadis

Anestopoulos

et al. 2018

Sci Rep

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In the present study, we have aimed to characterize the intrinsic, extrinsic and ER-mediated apoptotic induction by hyperthermia in an in vitro model of human malignant melanoma and furthermore, to evaluate its therapeutic effectiveness in an adjuvant therapeutic setting characterized by combinational treatments with non-targeted (Dacarbazine & Temozolomide) and targeted (Dabrafenib & Vemurafenib) drugs. Overall, our data showed that both low (43 °C) and high (45 °C) hyperthermic exposures were capable of inducing cell death by activating all apoptotic pathways but in a rather distinct manner. More specifically, low hyperthermia induced extrinsic and intrinsic apoptotic pathways both of which activated caspase 6 only as opposed to high hyperthermia which was mediated by the combined effects of caspases 3, 7 and 6. Furthermore, significant involvement of the ER was evident (under both hyperthermic conditions) suggesting its role in regulating apoptosis via activation of CHOP. Our data revealed that while low hyperthermia activated IRE-1 and ATF6 only, high hyperthermia induced activation of PERK as well suggesting that ultimately these ER stress sensors can lead to the induction of CHOP via different pathways of transmitted signals. Finally, combinational treatment protocols revealed an effect of hyperthermia in potentiating the therapeutic effectiveness of non-targeted as well as targeted drugs utilized in the clinical setting. Overall, our findings support evidence into hyperthermia’s therapeutic potential in treating human malignant melanoma by elucidating the underlying mechanisms of its complex apoptotic induction.

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“…Recent preclinical studies on MFH treatment of murine melanoma have shown encouraging results [14][15][16][17][18]. However, the control over the treatment intensity was rather limited, frequently leading to tissue necrosis, with the associated possible side effects that necrosis brings (such as vascular disruption and scarring), as well as the subsequent need for surgical removal of the dead tissue.…”

mentioning

confidence: 99%

Real-Time Tracking of Delayed-Onset Cellular Apoptosis Induced By Intracellular Magnetic Hyperthermia

Blanco-Andujar

Ortega

Southern

et al. 2015

Nanomedicine (Lond.)

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Highly focalised thermotherapy using a ferrimagnetic cement in the treatment of a melanoma mouse model by low temperature hyperthermia

Cited by 11 publications

References 46 publications

Hyperthermia Suppresses Post - In Vitro Proliferation and Tumor Growth in Murine Malignant Melanoma and Colon Carcinoma

Hyperthermia Suppresses Post - In Vitro Proliferation and Tumor Growth in Murine Malignant Melanoma and Colon Carcinoma

Hyperthermia induces therapeutic effectiveness and potentiates adjuvant therapy with non-targeted and targeted drugs in an in vitro model of human malignant melanoma

Real-Time Tracking of Delayed-Onset Cellular Apoptosis Induced By Intracellular Magnetic Hyperthermia

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