Electrochemotherapy associated with calcium electroporation in metastatic feline cutaneous malignant melanoma

Background: Calcium electroporation (CaEP) is a novel therapeutic treatment that has been studied for cancer due to itsselective killing cancer cells by necrosis and danger signals. Besides that, electrochemotherapy (ECT) is an effective local treatment that involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to thetumor. The combination with ECT and CaEP has been reported in literature suggesting that additional response of immunesystem could have been enhanced by electroporation with calcium. This case, report on the successful treatment with CaEPcombined with ECT for treatment of a regional metastasis in a feline model of malignant melanoma.Case: A 9-year-old, mixed breed cat was referred to the veterinary clinic with a 2-month history of cutaneous peripalpebralplaque lesion (0.19 cm³) and a submandibular lymph node enlargement (0.5 cm³). Incisional biopsy of the cutaneous lesionand fine-needle aspiration of submandibular lymph node confirmed a cutaneous melanoma with submandibular lymph nodemetastasis. Tumor staging was set in T1N1M0 according to WHO staging criteria. ECT for the primary lesion and lymphnode metastasis was proposed. For the ECT, bleomycin (15,000 UI/m²) application was performed intravenous followedby electroporation (8 pulses of 100 μs at 1000 V/cm, and 1 Hz) using a needle array electrode consisted of two parallelrows with six needles in each row. At 28-day post-ECT complete remission of the primary tumor and metastatic foci wasachieved. However, 120 days after ECT, recurrence was observed in submandibular and retropharyngeal...

Electrochemotherapy associated with calcium electroporation in metastatic feline cutaneous malignant melanoma

Background: Calcium electroporation (CaEP) is a novel therapeutic treatment that has been studied for cancer due to itsselective killing cancer cells by necrosis and danger signals. Besides that, electrochemotherapy (ECT) is an effective local treatment that involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to thetumor. The combination with ECT and CaEP has been reported in literature suggesting that additional response of immunesystem could have been enhanced by electroporation with calcium. This case, report on the successful treatment with CaEPcombined with ECT for treatment of a regional metastasis in a feline model of malignant melanoma.Case: A 9-year-old, mixed breed cat was referred to the veterinary clinic with a 2-month history of cutaneous peripalpebralplaque lesion (0.19 cm³) and a submandibular lymph node enlargement (0.5 cm³). Incisional biopsy of the cutaneous lesionand fine-needle aspiration of submandibular lymph node confirmed a cutaneous melanoma with submandibular lymph nodemetastasis. Tumor staging was set in T1N1M0 according to WHO staging criteria. ECT for the primary lesion and lymphnode metastasis was proposed. For the ECT, bleomycin (15,000 UI/m²) application was performed intravenous followedby electroporation (8 pulses of 100 μs at 1000 V/cm, and 1 Hz) using a needle array electrode consisted of two parallelrows with six needles in each row. At 28-day post-ECT complete remission of the primary tumor and metastatic foci wasachieved. However, 120 days after ECT, recurrence was observed in submandibular and retropharyngeal...(AU)

Radiation therapy for oral melanoma in dogs: a retrospective study / A utilização da radioterapia no melanoma oral de cães: Estudo retrospectivo

Our retrospective study evaluated the survival of 24 dogs with unresectable malignant melanoma treated with radiation therapy. Fifteen dogs were treated with radiation therapy (RT) and chemotherapy (CT), five with surgery followed by RT and CT, three with palliative RT, and one with electrochemotherapy associated with RT. All dogs were treated with an orthovoltage Stabilipan I. The protocol used was three or four weekly fractions of 8 Gy. Carboplatin was administered every 21 days, a total of four times. Five percent of dogs were classified as having stage I melanoma, 17% as stage II, 50% as stage III, and 17% as stage IV. Sixty-four percent had a partial response to treatment, 29% achieved complete remission, and 7% remained in a stable disease state. The mean survival time was 390 days for stage I, 286 days for stage II, 159 days for stage III, and 90 days for stage IV. We concluded that radiation therapy can be considered a viable alternative for the palliative treatment of canine oral melanoma.

O estudo retrospectivo analisou a sobrevida de 24 cães com melanomas irressecáveis tratados com radioterapia (RT). Quinze animais foram tratados com RT e quimioterapia (QT), 5 animais com cirurgia citoredutiva seguida por RT e QT, 3 animais com RT paliativa apenas e 1 animal com RT associada a 1 sessão de eletroquimioterapia. Os animais foram tratados com um equipamento de ortovoltagem Stabilipan I, e o protocolo foi de três a quatro frações semanais de 8 Gy. A quimioterapia consistiu de carboplatina administrada a cada 21 dias em um total de 4 aplicações. Apenas um animal (4%) foi classificado em estadio I, enquanto quatro (17%) estavam no estadio II, doze (50%) estavam no estadio III e quatro (29%) estavam no estadio IV. De maneira geral, 64% dos cães apresentaram resposta parcial, 29% remissão completa e 7% doença estável. O tempo médio de sobrevida foi de 390 dias no estádio I, 286 dias no estádio II, 159 dias no estádio III e 90 dias no estádio IV. A radioterapia deve ser considerada pelo clínico veterinário como alternativa para o tratamento de melanoma oral canino.

Radiation therapy for oral melanoma in dogs: a retrospective study / A utilização da radioterapia no melanoma oral de cães: Estudo retrospectivo

Our retrospective study evaluated the survival of 24 dogs with unresectable malignant melanoma treated with radiation therapy. Fifteen dogs were treated with radiation therapy (RT) and chemotherapy (CT), five with surgery followed by RT and CT, three with palliative RT, and one with electrochemotherapy associated with RT. All dogs were treated with an orthovoltage Stabilipan I. The protocol used was three or four weekly fractions of 8 Gy. Carboplatin was administered every 21 days, a total of four times. Five percent of dogs were classified as having stage I melanoma, 17% as stage II, 50% as stage III, and 17% as stage IV. Sixty-four percent had a partial response to treatment, 29% achieved complete remission, and 7% remained in a stable disease state. The mean survival time was 390 days for stage I, 286 days for stage II, 159 days for stage III, and 90 days for stage IV. We concluded that radiation therapy can be considered a viable alternative for the palliative treatment of canine oral melanoma.(AU)

O estudo retrospectivo analisou a sobrevida de 24 cães com melanomas irressecáveis tratados com radioterapia (RT). Quinze animais foram tratados com RT e quimioterapia (QT), 5 animais com cirurgia citoredutiva seguida por RT e QT, 3 animais com RT paliativa apenas e 1 animal com RT associada a 1 sessão de eletroquimioterapia. Os animais foram tratados com um equipamento de ortovoltagem Stabilipan I, e o protocolo foi de três a quatro frações semanais de 8 Gy. A quimioterapia consistiu de carboplatina administrada a cada 21 dias em um total de 4 aplicações. Apenas um animal (4%) foi classificado em estadio I, enquanto quatro (17%) estavam no estadio II, doze (50%) estavam no estadio III e quatro (29%) estavam no estadio IV. De maneira geral, 64% dos cães apresentaram resposta parcial, 29% remissão completa e 7% doença estável. O tempo médio de sobrevida foi de 390 dias no estádio I, 286 dias no estádio II, 159 dias no estádio III e 90 dias no estádio IV. A radioterapia deve ser considerada pelo clínico veterinário como alternativa para o tratamento de melanoma oral canino.(AU)

Anticancer properties of phospholipase A2 fromDaboia siamensis venom on human skin melanoma cells

Phospholipase A2 (PLA2) is a major component of theDaboia siamensis venom, which is able to hydrolyse the membrane of various cells. For this reason, the activity of PLA2was investigated regarding its pharmaceutical properties. This study was conducted to explore the pharmacological properties of a PLA2from Daboia siamensis (dssPLA2) venom on human skin melanoma cell line (SK-MEL-28). Methods dssPLA2 was isolated by ion exchange and gel filtration columns. Various concentrations of dssPLA2were investigated for cytotoxic activity and inhibition of migration on SK-MEL-28 cells. Cell death analysis, mRNA expression levels of Notch I-III and BRAF V600E genes were also determined. Results dssPLA2 exhibited cytotoxicity on SK-MEL-28 for 24 and 72 h as compared with untreated cells. However, it had no toxic effects on CCD-1064sk cells under the same conditions. dssPLA2 (0.25 and 0.5 g/mL) induced 17.16 and 30.60 % of apoptosis, while activated 6.53 and 7.05 % of necrotic cells. dssPLA2 at 0.25, 0.5, 1 and 2 g/mL could inhibit migration on SK-MEL-28 cells for 24 h by 31.06, 41.66, 50 and 68.75 %, respectively. The action of dssPLA2 significantly reduced the levels of Notch I and BRAF V600E genes expression on SK-MEL-28 cells compared with untreated cells at 72 h. Conclusions This study indicates that dssPLA2 had potential effects of apoptosis, necrosis, cytotoxicity and inhibition of migration on SK-MEL-28 cells. dssPLA2 could possibly be a selective agent that targets cancer cells without affecting normal cells.(AU)

Anticancer properties of phospholipase A2 fromDaboia siamensis venom on human skin melanoma cells

Phospholipase A2 (PLA2) is a major component of theDaboia siamensis venom, which is able to hydrolyse the membrane of various cells. For this reason, the activity of PLA2was investigated regarding its pharmaceutical properties. This study was conducted to explore the pharmacological properties of a PLA2from Daboia siamensis (dssPLA2) venom on human skin melanoma cell line (SK-MEL-28). Methods dssPLA2 was isolated by ion exchange and gel filtration columns. Various concentrations of dssPLA2were investigated for cytotoxic activity and inhibition of migration on SK-MEL-28 cells. Cell death analysis, mRNA expression levels of Notch I-III and BRAF V600E genes were also determined. Results dssPLA2 exhibited cytotoxicity on SK-MEL-28 for 24 and 72 h as compared with untreated cells. However, it had no toxic effects on CCD-1064sk cells under the same conditions. dssPLA2 (0.25 and 0.5 g/mL) induced 17.16 and 30.60 % of apoptosis, while activated 6.53 and 7.05 % of necrotic cells. dssPLA2 at 0.25, 0.5, 1 and 2 g/mL could inhibit migration on SK-MEL-28 cells for 24 h by 31.06, 41.66, 50 and 68.75 %, respectively. The action of dssPLA2 significantly reduced the levels of Notch I and BRAF V600E genes expression on SK-MEL-28 cells compared with untreated cells at 72 h. Conclusions This study indicates that dssPLA2 had potential effects of apoptosis, necrosis, cytotoxicity and inhibition of migration on SK-MEL-28 cells. dssPLA2 could possibly be a selective agent that targets cancer cells without affecting normal cells.