Photodynamic hyperthermal chemotherapy with indocyanine green: a novel cancer therapy for 16 cases of malignant soft tissue sarcoma

Sixteen cases of malignant soft tissue sarcoma (STS; 10 canines and six felines) were treated with a novel triple therapy that combined photodynamic therapy, hyperthermia using indocyanine green with a broadband light source, and local chemotherapy after surgical tumor resection. This triple therapy was called photodynamic hyperthermal chemotherapy (PHCT). In all cases, the surgical margin was insufficient. In one feline case, PHCT was performed without surgical resection. PHCT was performed over an interval of 1 to 2 weeks and was repeated three to 21 times. No severe side effects, including severe skin burns, necrosis, or skin suture rupture, were observed in any of the animals. No disease recurrence was observed in seven out of 10 (70.0%) dogs and three out of six (50.0%) cats over the follow-up periods ranging from 238 to 1901 days. These results suggest that PHCT decreases the risk of STS recurrence. PHCT should therefore be considered an adjuvant therapy for treating companion animals with STS in veterinary medicine.

Extracellular polysaccharide production by a strain of Pleurotus djamor isolated in the south of Brazil and antitumor activity on Sarcoma 180

Polysaccharides with medicinal properties can be obtained from fruiting bodies, mycelium and culture broth of several fungus species. This work was carried out in batch culture using a stirred tank reactor with two different initial glucose concentrations (40-50 g/L) and pH values (3.0-4.0) to enhance extracellular polysaccharides production by Pleurotus djamor UNIVILLE 001 and evaluate antitumor effect of intraperitonial administration of Pleurotus djamor extract on sarcoma 180 animal model. According to factorial design, the low pH value (pH 3.0) led to a gain of 1.6 g/L on the extracellular polysaccharide concentration, while glucose concentration in the tested range had no significant effect on the concentration of polysaccharide. With 40 g/L initial glucose concentration and pH 3.0, it was observed that yield factor of extracellular polysaccharide on substrate (Y P/S = 0.072) and maximum extracellular polysaccharide productivity (Q Pmax = 11.26 mg/L.h) were about 188% and 321% respectively higher than those obtained in the experiment performed at pH 4.0. Under these conditions, the highest values of the yield factor of biomass on substrate (Y X/S = 0.24) and maximal biomass productivity (Q Xmax = 32.2 mg/L.h) were also reached. In tumor response study, mean tumor volume on the 21th day was 35.3 cm³ in untreated group and 1.6 cm³ in treated group (p = 0.05) with a tumor inhibition rate of 94%. These impressive results suggests an inhibitory effect of P.djamor extract on cancer cells.

Chemotherapy in adult soft tissue sarcoma.

Soft tissue sarcomas (STSs) are rare and histologically diverse neoplasms. Recent results of various meta-analyses and development of newer drugs have changed the medical management of soft tissue sarcoma. This review gives an outline of chemotherapy and the newer targeted therapies for the same. We have carried out an extensive search in PubMed, Medline for almost all relevant articles concerning chemotherapy of soft tissue sarcoma. The available data from the literature is mainly composed of the most recent reviews, meta-analyses, phase II, and randomized phase III trials published in various peer reviewed journals and various international conferences. The role of neoadjuvant and adjuvant chemotherapy has been found to be controversial. The recent meta-analysis for adjuvant therapy in STSs has shown an increase in the overall survival with combination of ifosfamide and adriamycin. In locally advanced and metastatic STSs, single agent adriamycin remains the basic standard of medication. The combination of ifosfamide and adriamycin may also be used for rapid symptom relief and in patients planned for curative resection for metastases. Newer combinations of docetaxel and gemcitabine appear promising in selected subgroups, especially in leiomyosarcoma and malignant fibrous histiocytoma. Some recent developments include the European Union's approval of trabectedin for advanced STSs patients who had progressed on adriamycin and ifosfamide therapy. The future of mTOR inhibitors, insulin like growth factor receptor inhibitors and anti-angiogenic drugs appear quite promising. Newer methodologies such as, Bayesian adaptive randomization and inclusion of newer end points like progression-free rate, time of progression rate, and tumor growth rate will improve the results of sarcoma trials. At the end of each section we have also presented recommendations from *European Society of Medical Oncology and **National Comprehensive Cancer Network guidelines v.1.2009 for better correlation with the present literature.

Antitumor effects of ethanolic extracts from Sophora moorcroftiana seeds in mice

Sophora moorcroftiana [Wallich] is an endemic shrub species in Tibet, China, and is a plant with a great value in folk medicine. The previous studies had shown that the ethanolic [95%] extracts were much more effective than other extracts from Sophora moorcroftiana seeds on antiproliferative effects, inducing apoptosis in the human stomach cancer SGC-7901 cell line in vitro. To investigate the antitumor activity of the ethanolic extracts from Sophora moorcroftiana seeds, various doses of ethanolic extracts [200 mg/kg/d, 400 mg/kg/d, 800 mg/Kg/d] were administered via gavage to tumorbearing mice with S180 sarcoma cell for ten days. The weights of tumor tissue stripped from the left flank, TNF-alpha and IL-2 in blood-serum were tested and analyzed for photochemical composition, using standard procedures. The weight of tumor tissue was significantly decreased upon the treatment with ethanol extracts, but the decrease was more prominent in the group receiving ethanol extracts treatment at 800 mg/kg/d [1.35 +/- 0.21mg] and the inhibition rate on the growth of tumor tissue was higher [28.1%]. The structural changes of post-treatment in the tumor tissue by the ethanolic extracts at a dose of 800 mg/kg/d showed larger areas of necrosis and more significantly invaded lymphocytes. IL-2 and TNF-alpha in serum from the treated mice significantly increased in ethanolic extract-treated groups, compared with the untreated control animals. This suggested that the ethanolic extracts from Sophora moorcroftiana seeds had a weak antitumor role and in high concentration to tumor-bearing mice in vivo, the 95% ethanolic extracts was rather effective

In vitro anti-proliferation/cytotoxic activity of epingaione and its derivatives on the human SH-SY5Y neuroblastoma and TE-671 sarcoma cells / Actividad citotóxica antiproliferativa in vitro de la epingaiona y sus derivados, sobre el neuroblastoma humano sh-sy5y y las células del sarcoma te-671

Epingaione (4-Methyl-1-(5-methyl-2, 3,4,5-tetrahydro-[2,3']bifuranyl-5-yl)-pentan-2-one) was isolated as one of the major lipophilic secondary metabolites from the leaves and stems of Bontia daphnoides L. The compound gave 79.24and 50.83anti-proliferation/cytotoxic activity on the human SH-SY5Y neuroblastoma and TE-671 sarcoma cells in vitro at 50 pg/mL, respectively. Epingaione was transformed into eleven derivatives under laboratory conditions using ethanol, some gave greater anti-proliferation/cytotoxic activity on the cancer cell lines tested. One of the derivatives (compound 2) with enhanced cytotoxic activity was elucidated as 5'-Ethoxy-5-methyl-5-(4-methyl-2-oxo-pentyl)-2,3,4,5-tetrahydro-5'H-[2,3']bifuranyl-2'-one. Both epingaione and compound 2 caused an accumulation of arrested or dead SH-SY5Y neuroblastoma in the m-phase of the cell cycle as revealed by the m-phase specific marker KE 67.

La epingaiona (4-Metil-1-(5-metil-2,3,4,5-tetrahidro-[2,3']bifuranil-5-il)-pentan-2-uno) fue aislada como uno de los principales metabolitos lipofilicos secundarios de las hojas y tallos de Bontia daphnoides L. El compuesto produjo 79.24 % y 50.83 % de actividad citotóxica/anti-proliferación sobre el neuroblastoma humano SH-SY5Y y las células del sarcoma TE-671 in vitro a 50 µg/mL, respectivamente. La epingaiona fue transformada en once derivados en condiciones de laboratorio, utilizando etanol. Algunos produjeron mayor actividad citotóxica y antiproliferativa sobre las líneas celulares cancerosas sometidas a ensayo. Uno de los derivados (compuesto 2) de elevada actividad citotóxica fue identificado como 5'-Etoxi-5-metil-5-(4-metil-2-oxo-pentil)-2,3,4,5-tetrahidro-5'H- [2,3']bifuranil-2'-uno. Tanto la epingaiona como el compuesto 22 causaron una acumulación de neuroblastomas SH-SY5Y muertos o detenidos en la fase m del ciclo celular, según lo revela el marcador KE 67 específico de la fase m.

Primitive cardiac sarcomas: about 2 cases

The cardiac sarcomas, although very rare, represent the quasi-totality of the primitive sly tumors of the heart. It is about a retrospective study of two cases of cardiac sarcomas operated in Sahloul university hospital of Sousse. Cases it is about a woman and a man: The respective ages were 22 and 45 years. The clinical pattern of the patients was polymorphic and the diagnosis put by cardiac echography. Both patients had a surgical resection and a chemotherapy. Both patients died in 13 and 18 months after the diagnosis. Because of the extreme rarity of the cardiac sarcomas, there is no precise therapeutic strategy. The only consensus concerns the surgery as soon as the diagnosis of cardiac tumor is put. The prognosis of these tumors is extremely redoubtable with a survival which does not exceed 2 years after the beginning of the symptomatology

Atividade antitumoral de indigofera suffruticosa / Antitumoractivity of indigofera suffruticosa

Objetivo: Avaliar a atividade antitumoral de extratos aquosos por infusão e maceração de folhas de Indigofera suffruticosa (Fabaceae) em camundongos albinos suíços. Materiais e Métodos: Em trinta camundongos albinos suíços foram injetados via i.p. 0,3 ml de células do Sarcoma 180 (aproximadamente 3x106 células). Após 48 horas do implante, a quimioterapia foi iniciada com o uso do extrato aquoso de folhas de I. suffruticosa por infusão e maceração em concentrações diárias de 50mg/kg i.p. por 7 dias consecutivos. Para o grupo controle, 0,2 ml/Kg i.p. de solução salina foi administrada. No oitavo dia, os camundongos foram sacrificados para estudos tumorais. Os dados foram analisados utilizando-se Análise de Variância (ANOVA) ou o teste de Kruskal-Wallis. P<0,001 foi usado para rejeição da hipótese de nulidade. Resultados: A atividade antitumoral dos extratos aquosos por infusão (64,5%) e maceração (62,6%) sob Sarcoma 180 em camundongos na dose de 50 mg/kg i.p., baseada na baixa ordem de toxicidade, foi comparada com o grupo controle que mostrou desenvolvimento tumoral de 100% Conclusão: O extrato aquoso de folhas de I. suffruticosa apresenta propriedade antitumoral.

Histamine combined with melphalan in isolated limb perfusion for the treatment of locally advanced soft tissue sarcomas: preclinical studies in rats

OBJETIVO: Avaliar o potencial benéfico da histamina combinada ao melfalano, na perfusão de membro isolado (PMI), como alternativa à combinacão TNF-alfa mais melfalano, no tratamento de sarcomas de partes moles irressecaveis em extremidades, em ratos de linhagem Brown Norway (BN). MÉTODOS: 20 ratos BN foram submetidos a implantacão de fragmentos de fibrosarcoma singênico BN-175 na pata traseira direita. Em cerca de 7-10 dias o tumor atingiu um diâmetro médio de 12-15 mm e foram aleatóriamente divididos em quatro grupos (controle, melfalano,histamina em doses progessivas combinada ao melfalano e histamina) sendo submetidos a PMI experimental por 30 minutos. Os tumores foram então medidos diariamente com o uso de paquímetro e o volume tumoral calculado. RESULTADOS: As curvas de resposta mostram um efeito significativo da combinacão de Histamina na concentracão de 200 mg/mL ao melfalano, com 66% de resposta global incluindo 33% de respostas completas (p < 0.01). Não houve efeitos colaterais sistêmicos e localmente apenas edema leve e transitório nos animais tratados com histamine. CONCLUSAO: A histamina em combinacão com o melfalano apresenta um efeito promissor na PMI garantindo maiores investigacões do seu mecanismo de acão e do seu potencial uso na perfusão de órgãos.

Stromal sarcoma of breast: a case report.

A 34 years unmarried female was admitted with an ulcerated foul smelling growth in her right breast. On examination the fungating mass measured 17.5 cm x 15 cm in central and lower part of right breast involving the nipple and areola. The ulcer was covered with slough and rest part of the breast appeared bosselated. Her Hb was 4 g/dl and incision biopsy from the margin of the tumour showed histology of sarcoma. The patient was infused 6 units of blood and right sided total mastectomy was done. Histopathological examination confirmed it was a case of stromal sarcoma of breast. Chemotherapy was started with vincristine, adriamycin and cylophosphamide. The patient was doing well in next follow-up.

Sarcomas de partes moles primários de tronco e extremidades em lactentes / Primary trunk and extremities soft sarcomas in infants

Durante o período de janeiro de 1970 a dezembro de 1991, 30 lactentes portadores de sarcoma de partes moles primário do tronco e extremidades foram admitidos no Departamento de Pediatria do Hospital do Câncer. Treze neoplasias eram originárias da parede torácica e abdominal; 13, de membros inferiores; e quatro, de membros superiores. Dez pacientes apresentavam doença localizada e 20, doença avançada. Em relaçäo ao tipo histológico, 18 tumores foram classificados como sarcomas de partes moles näo rabdomiossarcoma. Quinze crianças estäo vivas sem evidência de doença; uma, viva com segundo tumor (LLA); três foram perdidos de seguimento e 11 foram a óbito (10 por progressäo de doença e um por toxicidade). A intervençäo cirúrgica, a quimioterapia e a radioterapia utilizadas isoladamente ou combinadas na dependência do tipo histológico e extensäo da doença nos pacientes portadores de sarcomas de partes moles foram responsáveis pelo aumento da taxa de cura nesses casos. As características intrínsecas do lactente fazem com que cada vez mais esses recursos terapêuticos venham a ser aprimorados a fim de que os efeitos colaterais decorrentes do tratamento sejam evitados ou minimizados. Ao analisarmos lactentes portadores de sarcomas de partes moles, pudemos avaliar os efeitos deletérios decorrentes da terapêutica preconizada nos anos 70 e 80, atentando para o fato de que cada vez mais, cura e qualidade de vida devem caminhar paralelamente. Os avanços em biologia molecular poderÝo, num futuro próximo, selecionar pacientes de maior ou menor risco, preconizando tratamentos mais e menos agressivos na dependência do prognóstico. O fator prognóstico mais importante foi a extensäo da doença ao diagnóstico.

Diagnóstico y tratamiento de los sarcomas de partes blandas / Soft tissue sarcomas, diagnosis and treatment

En este artículo se presentan algunos conocimientos básicos y avanzados sobre el estudio de los carcomas, así como de su biología y manejo multidisciplinario. También se presenta parte de las experiencias que hemos adquirido en el Instituto Nacional de Cancerología

Sarcomas de cabeza y cuello / Head and neck sarcomas

Diversos tipos de sarcomas existen en el área de cabeza y cuello, aunque por lo general son neoplasias muy raras. Se localizan en esta región el 15 por ciento de todos los sarcomas, pero representan apenas el 1 por ciento de los tumores de cabeza y cuello. Su historia natural es similar a los sarcomas del resto del cuerpo; sin embargo, dada su localización, presentan mayor dificultad quirúrgica de control local, por lo que los pacientes tienen una expectativa de vida más pobre. A diferencia de sarcomas en otra localización, éstos metastatizan preferentemente a pulmones. Se dividen en sarcomas de alto, intermedio y bajo grado, y en no clasificables. El principal factor pronóstico es el grado histológico; otros son el tamaño de la lesión, tipo de excisión (si fue o no completa) y parámetros morfológicos: (número de mitosis, pleomorfismo nuclear y necrosis). En la serie del Instituto Nacional de Cancerología de México se identificaron 27 casos (registrados entre 1082 a 1993), 23 de éstos correspondieron a sarcomas de alto grado y los cuatro restantes fueron de grado intermedio. En nuestra serie, el grado histológico también fue el principal factor pronóstico. Las estirpes de schwannoma maligno y rabdomiosarcoma fueron las variedades más frecuentes, a cada una de ellas correspondieron ocho casos (59 por ciento); también se documentarn cinco de angiosarcoma. El antro maxilar y el cuello fueron los sitios de presentación registrados con mayor frecuencia. La cirugía fue la alternativa de tratamiento en los sarcomas menores a 5 cm; mientras que la modalidad combinada se cirugía y radioterapia lo fue para lesiones mayores de 5 cm muy avanzadas. A los enfermos con tumores resecados incompletamante se les administó quimioterapia paliativa. El papel de la cirugía en sarcomas de cabeza y cuello es especialmente dificil debido a limitaciones anatómicas que dificultan dar márgenes quirúrgicos adecuado, a lo cual se suma el inherente compromiso estético y funcional. A esto habría que agregar que nuestros casos se presentaron con tumores de grandes dimensiones y ya en estadios avanzados. En conclusión, la experiencia documentada en la literatura y la obtenida en nuestro instituto apoyan el concepto de terapia combinada: cirugía y radioterapia en el tratamiento de sarcomas de alto grado resecados incompletamente; para pacientes con lesiones pequeñas y de grado intermedio...

Momento atual do tratamento dos sarcomas osseos de alta malignidade / Present status of the treatment of high grade bone sarcomas

Os autores apresentam uma revisao das alteracoes ocorridas no tratamento dos sarcomas osseos de alta malignidade nos ultimos 20 anos. Sao discutidos a abordagem multidisciplinar para o controle local e sistemico destes tumores principalmente a quimioterapia neoadjuvante que levou a um aumento na sobrevida global nao apenas para o osteossarcoma como tambem para o sarcoma de Ewing. Apresentam as possibilidades para a reconstituicao do membro apos resseccao ampla que incluem endoprotese nao convencional e enxerto autologo e de banco de osso

Radioterapia en sarcoma de los tejidos blandos / Radiotherapy in soft tissue carcoma

El presente artículo es una breve revisión de las contribuciones más notables que ha hecho la radiotrapia al campo de la terapéutica de los sarcomas de los tejidos blandos. De antemano se sabe que el manejo clásico de este tipo de neoplasias es quirúrgico y que, según la amplitud del procedimiento empleado, la recurrencia local varía desde un 90 por ciento para la biopsia excisional únicamente, hasta un 18 por ciento para la cirugía radical o amputación. En algunas series se informa que más del 50 por ciento de pacientes sufrieron de cirugías mutilantes. En pacientes casi siempre inoperables, la radioterapia como tratamiento único resulta en índices de control local del 29 al 33 por ciento. Combinar radioterapia preoperatoria y cirugía brinda control local de 90 a 97 por ciento. Con la aplicación de la radioterapia después de la cirugía se logra control local de 78 a 91 por ciento; la tasa de falla local es del 18.5 por ciento; la preservación funcional del miembro afectado puede ser hasta de 84.7 por ciento. La radioterapia intraoperatoria, con braquiterapia de carga diferida con Ir-192, es otra modalidad terapéutica exitosa, sobre todo en los sarcomas de alto grado en los que se obtiene control local a cinco años hasta del 90 por ciento. El tratamiento combinado ciugía más radioterapia en cualquiera de sus variantes es el mayor avance registrado en el manejo de los sarcomas de los tejidos blandos en las últimas décadas

Osteogenic sarcoma: initial experience at the Shaukat Khanum Hospital

Osteogenic sarcoma is a malignant tumour of bone in which tumour cells form neoplastic osteoid or bone or both. It is not a very uncommon tumour. We saw 66 patients at the Shaukat Khanum Paediatric Oncology Department between January 1995 to November 1996. There was a male preponderance [73%]. Mean age at presentation was 14.38 years. The average tumour length and width at the time of presentation was 21.2cm and 17.45cm respectively. The common site was femur 44.0%. Metastases were present in 45% at presentation. Serum Alkaline Phosphatase was elevated. Majority [79%] of the patients had no treatment prior to presentation. All the poor prognostic factors were present at presentation in almost all the patients. All received neo- adjuvant chemotherapy and all the patients except one were offered amputations. Sixty five percent patients have been lost to follow up

Tratamento dos sarcomas de partes moles / Soft tissue sarcomas - treatmnet

Os sarcomas de partes moles sao raros,correspondendo a menos de 1 por cento dos casos de tumores malignos,embora essa incidência aumente para 6,5 por cento em idades abaixo de 15 anos.Em funçao da raridade ,os cirurgioes se defrontam com esse diagnostico apenas ocasionalmente.Devido à variabilidade de localizaçao e de agressividade, o tratamento dessas doenças representa um grande desafio.Localizam-se preferencialmente nas extremidades,com 58 por cento dos casos,depois no tronco(30 por cento) e na cabeça e pescoço(12 por cento).Apresentam-se como massa que crescem no subcutâneo, na intimidade de musculos esqueléticos,no retroperitônio ou madiastino ou,ainda,em víceras.As bases do tratamento cirurgico dos sarcomas de partes moles estao bem estabelecidas:ressecçao completa em monobloco do tumor,que deve ser envolvido por um generoso envelope,com 2 a 4 cm de espessura,de tecidos normais.Quando sao feitas excisoes marginais,isto é,quando o tumor é ressecado imediatamente por fora de sua pseudocápsula,as recidivas ocorrerao em 90 por cento a 100 por cento dos casos.Apenas as ressecçoes locais radicais abaixam esse índice para 10 a 15 por cento.A radioterapia adjuvante tem diminuido em algumas situaçoes as recidivas locais.A quimioterapia ddjuvante tem sido objeto de controversias.Existem séries em que a combinaçao de doxorubicina,ciclofosfamida e metotrexate mostram melhora significativa no período livre de doença em sarcomas de alto grau.Outros estudos,entretanto,nao confirmam tais resultados.Na avaliaçao prognostica dos sarcomas de partes moles é fundamental a determinaçao de seu grau,cuja importância supera em muito a do tipo histologico e o tamanho do tumor.