1 research outputs found
Study of photodynamic efficiency of the hematoporphyrin conjugated with antibody to VEGF in mouse Lewis carcinoma
Aim: To examine photodynamic antitumor and anti-metastatic effect of hematoporphyrin, conjugated with antibodies to VEGF in comparison with native hematoporphyrin in experiments with high metastatic, angiogenesis-independent Lewis carcinoma (LLC) and its low metastatic angiogenesis-dependent variant β LLC/R9. Methods: Mice with LLC or with LLC/R9 were treated by photodynamic therapy (PDT) using new photosensitizer β hematoporphyrin conjugated with antibodies to VEGF, in comparison with hematoporphyrin or aminolevulinic acid. Tumor growth indices and metastasis incidence were calculated. Results: Strong antitumor effect of PDT with new conjugate was demonstrated β delay of tumor development by 70% whereas native hematoporphyrin with the same treatment regime did not show any significant effect. Most pronounced effect of conjugate was demonstrated on the growth and metastasing of LLC/R9, which was characterized by the resistance to chemotherapeutic drugs. Slowdown of the tumor growth β up to complete regression β was detected already at the third day after PDT and, on the average was about 70% of control values. Non-conjugated hematoporphyrin under parameters chosen did not cause antitumor effect. Metastases calculation demonstrated that total metastatic volume reduced by seven times in conjugate group and by 3.5 times in hematoporphyrin group. Conclusion: Hematoporhyrin conjugate studied had high photodynamic antitumor activity. Taking into consideration substantial prevalence in clinical practice of drug-resistant tumors and angiogenesis-dependent character of metastasis process, further study and application of photosensitizers, conjugated with antibodies to VEGF, may help to improve the clinical outcomes.Π¦Π΅Π»Ρ: ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΠ³ΠΎ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠ³ΠΎ ΠΈ Π°Π½ΡΠΈΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ Π³Π΅ΠΌΠ°ΡΠΎΠΏΠΎΡΡΠΈΡΠΈΠ½Π°, ΠΊΠΎΠ½ΡΡΠ³ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ
Ρ Π°Π½ΡΠΈΡΠ΅Π»Π°ΠΌΠΈ ΠΊ VEGF, ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ ΠΈΡΡ
ΠΎΠ΄Π½ΡΠΌ Π³Π΅ΠΌΠ°ΡΠΎΠΏΠΎΡΡΠΈΡΠΈΠ½ΠΎΠΌ ΠΏΡΠΈ ΡΠΎΡΠΎΠ΄ΠΈΠ½Π°ΠΌΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ Π²ΡΡΠΎΠΊΠΎΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ
Π·Π°Π²ΠΈΡΠΈΠΌΠΎΠΉ ΠΎΡ Π°Π½Π³ΠΈΠΎΠ³Π΅Π½Π΅Π·Π° ΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌΡ ΠΡΡΠΈΡ (LLC) ΠΈ Π΅Π΅ Π½ΠΈΠ·ΠΊΠΎΠΌΠ΅ΡΠ°ΡΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΠΎΠ³ΠΎ ΠΎΡ Π°Π½Π³ΠΈΠΎΠ³Π΅Π½Π΅Π·Π° Π²Π°ΡΠΈΠ°Π½ΡΠ°
β LLC/R9. MeΡΠΎΠ΄Ρ: ΠΌΡΡΠ°ΠΌ Ρ LLC ΠΈΠ»ΠΈ Ρ LLC/R9 ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΠ»ΠΈ ΡΠΎΡΠΎΠ΄ΠΈΠ½Π°ΠΌΠΈΡΠ΅ΡΠΊΡΡ ΡΠ΅ΡΠ°ΠΏΠΈΡ (Π€ΠΠ’) Ρ Π½ΠΎΠ²ΡΠΌ ΡΠΎΡΠΎΡΠ΅Π½ΡΠΈΠ±ΠΈΠ»ΠΈΠ·Π°ΡΠΎΡΠΎΠΌ
β Π³Π΅ΠΌΠ°ΡΠΎΠΏΠΎΡΡΠΈΡΠΈΠ½ΠΎΠΌ, ΠΊΠΎΠ½ΡΡΠ³ΠΈΡΠΎΠ²Π°Π½Π½ΡΠΌ Ρ Π°Π½ΡΠΈΡΠ΅Π»Π°ΠΌΠΈ ΠΊ VEGF, ΠΏΡΠΈ ΡΡΠ°Π²Π½Π΅Π½ΠΈΠΈ Ρ ΠΈΡΡ
ΠΎΠ΄Π½ΡΠΌ Π³Π΅ΠΌΠ°ΡΠΎΠΏΠΎΡΡΠΈΡΠΈΠ½ΠΎΠΌ
ΠΈΠ»ΠΈ Π°ΠΌΠΈΠ½ΠΎΠ»Π΅Π²ΡΠ»ΠΈΠ½ΠΎΠ²ΠΎΠΉ ΠΊΠΈΡΠ»ΠΎΡΠΎΠΉ. Π£ΡΠΈΡΡΠ²Π°Π»ΠΈ ΡΠ°Π·ΠΌΠ΅ΡΡ ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ ΠΈ ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ ΠΌΠ΅ΡΠ°ΡΡΠ°Π·ΠΎΠ². Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ: ΠΏΡΠΈ Π€ΠΠ’ Ρ ΠΊΠΎΠ½ΡΡΠ³Π°ΡΠΎΠΌ
ΠΎΡΠΌΠ΅ΡΠ΅Π½ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΠΉ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΡΠΉ ΡΡΡΠ΅ΠΊΡ β Π·Π°Π΄Π΅ΡΠΆΠΊΠ° ΡΠΎΡΡΠ° ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ Π½Π° 60β63%, Π² ΡΠΎ Π²ΡΠ΅ΠΌΡ ΠΊΠ°ΠΊ ΠΈΡΡ
ΠΎΠ΄Π½ΡΠΉ Π³Π΅ΠΌΠ°ΡΠΎΠΏΠΎΡΡΠΈΡΠΈΠ½
Π² Π²ΡΠ±ΡΠ°Π½Π½ΡΡ
ΡΡΠ»ΠΎΠ²ΠΈΡΡ
Π·Π½Π°ΡΠΈΠΌΠΎΠ³ΠΎ ΡΡΡΠ΅ΠΊΡΠ° Π½Π΅ ΠΎΠΊΠ°Π·ΡΠ²Π°Π». ΠΠ°ΠΈΠ±ΠΎΠ»ΡΡΠ΅Π΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΠΊΠΎΠ½ΡΡΠ³Π°Ρ ΠΎΠΊΠ°Π·ΡΠ²Π°Π» Π½Π° ΡΠΎΡΡ ΠΈ
ΠΌΠ΅ΡΠ°ΡΡΠ°Π·ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π²Π°ΡΠΈΠ°Π½ΡΠ° ΠΎΠΏΡΡ
ΠΎΠ»ΠΈ LLC/R9, Ρ
Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·ΡΡΡΠ΅Π³ΠΎΡΡ ΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΠΎΡΡΡΡ ΠΊ Ρ
ΠΈΠΌΠΈΠΎΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°ΠΌ. ΠΠ°Π΄Π΅ΡΠΆΠΊΡ ΠΎΠΏΡΡ
ΠΎΠ»Π΅Π²ΠΎΠ³ΠΎ
ΡΠΎΡΡΠ° β Π²ΠΏΠ»ΠΎΡΡ Π΄ΠΎ ΠΏΠΎΠ»Π½ΠΎΠΉ ΡΠ΅Π³ΡΠ΅ΡΡΠΈΠΈ β ΠΎΡΠΌΠ΅ΡΠ°Π»ΠΈ ΡΠΆΠ΅ Π½Π° 3-ΠΈ ΡΡΡΠΊΠΈ ΠΏΠΎΡΠ»Π΅ Π€ΠΠ’ ΠΈ Π² ΠΎΠ±ΡΠ΅ΠΌ ΠΎΠ½Π° ΡΠΎΡΡΠ°Π²Π»ΡΠ»Π° ΠΎΠΊΠΎΠ»ΠΎ 70%
ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ ΠΊΠΎΠ½ΡΡΠΎΠ»Π΅ΠΌ. ΠΠΎΠ΄ΡΡΠ΅Ρ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π° ΠΌΠ΅ΡΠ°ΡΡΠ°Π·ΠΎΠ² ΠΏΠΎΠΊΠ°Π·Π°Π», ΡΡΠΎ ΠΎΠ±ΡΠΈΠΉ ΠΎΠ±ΡΠ΅ΠΌ ΠΌΠ΅ΡΠ°ΡΡΠ°Π·ΠΎΠ² ΡΠ½ΠΈΠ·ΠΈΠ»ΡΡ Π² 7 ΡΠ°Π· Π² Π³ΡΡΠΏΠΏΠ΅
Ρ ΠΊΠΎΠ½ΡΡΠ³Π°ΡΠΎΠΌ ΠΈ Π² 3,5 ΡΠ°Π·Π° Π² Π³ΡΡΠΏΠΏΠ΅ Ρ Π³Π΅ΠΌΠ°ΡΠΎΠΏΠΎΡΡΠΈΡΠΈΠ½ΠΎΠΌ. ΠΡΠ²ΠΎΠ΄Ρ: ΠΏΡΠΈΠ½ΠΈΠΌΠ°Ρ Π²ΠΎ Π²Π½ΠΈΠΌΠ°Π½ΠΈΠ΅ Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅ ΠΏΡΠ΅Π²Π°Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅
Π² ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΏΡΠ°ΠΊΡΠΈΠΊΠ΅ Ρ
ΠΈΠΌΠΈΠΎΡΠ΅Π·ΠΈΡΡΠ΅Π½ΡΠ½ΡΡ
ΠΎΠΏΡΡ
ΠΎΠ»Π΅ΠΉ, Π° ΡΠ°ΠΊΠΆΠ΅ Π·Π°Π²ΠΈΡΠΈΠΌΠΎΠ³ΠΎ ΠΎΡ Π°Π½Π³ΠΈΠΎΠ³Π΅Π½Π΅Π·Π° Ρ
Π°ΡΠ°ΠΊΡΠ΅Ρ ΠΌΠ΅ΡΠ°ΡΡΠ°Π·ΠΈΡΠΎΠ²Π°Π½ΠΈΡ,
Π΄Π°Π»ΡΠ½Π΅ΠΉΡΠ΅Π΅ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΠΈ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΡΠΎΡΠΎΡΠ΅Π½ΡΠΈΠ±ΠΈΠ»ΠΈΠ·Π°ΡΠΎΡΠΎΠ², ΠΊΠΎΠ½ΡΡΠ³ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
Ρ Π°Π½ΡΠΈΡΠ΅Π»Π°ΠΌΠΈ ΠΊ VEGF, ΠΌΠΎΠΆΠ΅Ρ ΡΠ»ΡΡΡΠΈΡΡ
ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΡ Π»Π΅ΡΠ΅Π½ΠΈΡ