Immunohistochemical expression of CD-10, BCL-6 and MUM-1 antibodies and immediate clinical response in patients of diffuse large B-cell lymphomas after six cycles of chemotherapy

To determine the expression of CD-10, BCL-6 and MUM-1 in patients with diffuse large B-cell lymphoma [DLBCL] and its association with immediate clinical response after six cycles of CHOP chemotherapy. Analytical study. Armed Forces Institute of Pathology [AFIP], Rawalpindi in collaboration with Nuclear medicine, Oncology and Radiotherapy Institute [NORI], Islamabad from September 2010 to September 2011. CD-10, BCL-6 and MUM-1 antibodies were applied on cases diagnosed as DLBCL. Immediate clinical response was noted after 6 cycles of chemotherapy with the help of oncologist and divided into complete response, partial response, stable disease and relapse/ progression. Patient's age, results of expression of CD-10, BCL-6 and MUM-1 and results of immediate clinical response to chemotherapy were noted. Regarding analysis of prognostic markers [CD-10, BCL-6 and MUM-1], chi-square test was used for immediate clinical response to chemotherapy in DLBCL. CD-10 was positive in 40% cases, BCL-6 in 58.7% cases and MUM-1 was positive in 46.7% cases. About 41.3% of patients showed complete response, 10.6% partial response, 17.3% stable disease and 30.8% showed relapse/progression. CD-10 expression in DLBCL was associated with better immediate clinical response [p = 0.011] whereas MUM-1 expression in DLBCL was associated with poor immediate clinical response [p < 0.0001]. However, there was no statistically significant association of BCL-6 with immediate clinical response [p = 0.22]. DLBCL shows expression of CD-10, BCL-6 and MUM-1 in nearly fifty percent of the cases. CD-10 is associated with good whereas MUM is associated with poor response. However, there was no association of BCL-6 with immediate clinical response

Associação do quimioterápico daunorrubicina a uma nanoemulsão rica em colesterol: estudos de regressão tumoral e farmacocinética / Association of the chemotherapeutic agent daunorubicin a cholesterol-rich nanoemulsion: regression studies pharmacokinetics and tumor

A nanoemulsão lipídica (LDE) se concentra nas células neoplásicas e pode ser utilizada como transportador de derivado lipofílico da daunorrubicina, como o Noleil- daunorrubicina (oDNR). Neste estudo, a LDE-oDNR foi preparada por homogeneização em alta pressão e sua toxicidade e atividade anti-tumoral testadas. A associação LDE-oDNR teve rendimento elevado e permaneceu estável por longo período. Em camundongosC57BL/6J, a dose máxima tolerada (DMT) foi 65 vezes maior e a DL50 48 vezes maior no tratamento LDE-oDNR comparado ao tratamento DNR comercial, resultando em alta redução da toxicidade. Em camundongos implantados com células de melanoma B16, a preparação LDE-oDNR (7,5 mol/kg) levou a redução de 59 ± 2% do crescimento do tumor comparado a redução de 23 ± 2% para o tratamento DNR comercial na mesma dose (p<0,001). A probabilidade de sobrevida teve aumento pronunciado nos animais tratados com LDE-oDNR comparado à DNR comercial (p <0,01). Além disso, apenas 30% dos animais portadores de melanoma submetidos ao tratamento com LDE-oDNR apresentaram metástases, comparado a 82% quando tratados com DNR comercial. Uma forte redução de toxicidade também foi observada pela redução da anemia e leucopenia nos animais tratados com LDE-oDNR, em comparação com DNR comercial. A preparacao LDE-oDNR foi eficaz também no quadro de trombocitose induzida por tumor. Os testes com fragmentos extraídos de tumores dos animais tratados mostraram que a LDE-oDNR foi mais eficaz na destruição das células neoplásicas comparado ao tratamento DNR comercial (9% de células viáveis com tratamento LDE-oDNR, 27% sob tratamento DNR). O estudo mostrou que o tratamento proposto com o derivado ODNR associado à nanoemulsão (LDE-oDNR) é efetivo no combate às células tumorais, seletivo, menos tóxico e melhor tolerado. Os estudos de farmacocinética e biodistribuição somam a este protocolo informações importantes relacionadas às propriedades de absorção, distribuição, metabolismo e excreção...

A lipidic nanoemulsion (LDE) that concentrates in neoplastic cells can be used as vehicle to daunorubicin lipophylic derivatives, such as N-oleyl-daunorubicin (oDNR). Here, LDE-oDNR was prepared by high pressure homogenization to test toxicity and anti-tumor activity. LDE-oDNR association yield was high and stable for long period. In mice, maximum tolerated dose was 65 and LD50 was 48-fold greater in LDE-oDNR than in commercial DNR treatment, showing very strong toxicity reduction. In melanoma B16-tumor bearing mice, LDE-oDNR (7.5 mol/Kg) reduced tumorgrowth by of 59±2%, and DNR by only 23±2% at same dose level (p<0.001). Survival was pronouncedly increased in LDE-oDNR compared to DNR treatment (p<0.01). Furthermore, the number of melanoma-bearing mice with metastasis was 30% under LDE-oDNR, compared to 82% under DNR treatment. Strong reduction of toxicity was also observed by reduction of anemia and leucopenia under LDE-oDNR, compared to commercial DNR tumor-induced thrombocytosis was more effective with LDE-oDNR than with DNR. Tests with fragments extracted from tumors of treated animals showed that LDE-oDNR was more effective in killing neoplastic cells than DNR (9% of viable cells under LDE-oDNR; 27% under DNR). The pharmacokinetics and biodistribution studies add important information to this protocol related to the properties of absorption, distribution, metabolism and excretion of the formulation under study compared to free DNR. The remarkable toxicity reduction and increase in pharmacological action supports novel LDE-oDNR as a promising weapon in cancer treatment.

Associação de derivados do quimioterápico daunorrubicina à nanoemulsão lipídica que se liga aos receptores da LDL: estudos pré-clínicos / Daunorubicin chemotherapic derivatives association to a lipidic nanoemulsion that binds to LDL receptors: pre-clinical studies

A daunorrubicina é utilizada no tratamento da leucemia mielóide aguda cujo uso é muito limitado devido à alta cardiotoxicidade. Neste trabalho foi feita a sua modificação química e associação à uma nanoemulsão lipídica que se liga aos receptores da LDL, a LDE, como um meio de reduzir a toxicidade do fármaco mantendo o efeito antitumoral. Dois derivados da daunorrubicina foram produzidos, caracterizados, associados à LDE e analisados quanto à taxa de associação, diâmetro da partícula e estabilidade no plasma. A LDE-N-oleil daunorrubicina foi menos cardiotóxica e menos letal em camundongos do que a daunorrubicina comercial. Houve efeito citotóxico em células tumorais, embora um pouco menor do que o da daunorrubicina comercial / Daunorubicin is a chemotherapic used in acute myeloid leukemia treatment which use is many limited due to high cardiotoxicity. Here we did the chemical modification of the drug and its association with a lipidic nanoemulsion that binds to LDL receptors, LDE, as a way of decreasing drug toxicity and, at the same time, keeping the antitumoral effect. Two N-daunorubicin derivatives were produced, chemically characterized and associated with LDE particles. The partitioning coefficient, LDE association rate, particle size and plasma stability was determined for each derivative. LDE-N-oleil daunorubicin was less cardiotoxic and had a higher lethal doses in Swiss mice than commercial daunorubicin. The antitumoral effect to leukemic cells was kept although it had been lower than commercial daunorubicin...