Cytotoxic effect of hydroalcoholic extract of Cota tinctoria (L) J. Gay on AGS and Hep-G2 cancer cell lines / Efecto citotóxico del extracto hidroalcohólico de Cota tinctoria (L) J. Gay sobre líneas celulares de cáncer AGS y Hep-G2

Cota tinctoria is a medicinal plant which has been used for management of cancer in folk medicine of various regions. The aim of present study is to investigate cytotoxic activity of different concentrations of hydroalcoholic extract of C. tinctoria flowers on gastric (AGS) and liver (Hep-G2) cancer cell lines as well as Human Natural GUM fibroblast (HUGU) cells. Cell mortality rates were examined after 24, 48 and 72 h incubations using the MTT assay. IC50of extract on AGS cells after 24, 48 and 72h was 1.46, 1.29 and 1.14 µg/mL respectively. The extract demonstrated IC50 of 5.15, 3.92 and 2.89 µg/mL on Hep-G2 cells after 24, 48 and 72 h respectively. No cytotoxic effect was detected on HUGU (Human Natural GUM fibroblast) cells. C. tinctoria seems to have a promising potential to be considered as a source for anticancer drug discovery. However, more experimental and clinical studies are required.

Cota tinctoria es una planta medicinal que se ha utilizado para el tratamiento del cáncer en la medicina popular de varias regiones. El objetivo del presente estudio es investigar la actividad citotóxica de diferentes concentraciones de extracto hidroalcohólico de flores de C. tinctoria en líneas celulares de cáncer gástrico (AGS) e hígado (Hep-G2), así como en células de fibroblasto GUM humano natural (HUGU). Se examinaron las tasas de mortalidad celular después de incubaciones de 24, 48 y 72 h utilizando el ensayo MTT. La CI50 del extracto en células AGS después de 24, 48 y 72 h fue de 1,46; 1,29 y 1,14 µg respectivamente. El extracto demostró una CI50 de 5,15, 3,92 y 2,89 µg/mL en células Hep-G2 después de 24, 48 y 72 h, respectivamente. No se detectó ningún efecto citotóxico en las células HUGU (fibroblasto GUM humano natural). C. tinctoria parece tener un potencial prometedor para ser considerada como una fuente de descubrimiento de fármacos contra el cáncer. Sin embargo, se requieren más estudios experimentales y clínicos.

Investigation of effect of paclitaxel on netrin 1 and factor 8 in Ehrlich solid tumors / Investigación del efecto del paclitaxel en netrina 1 y factor 8 en tumores sólidos de Ehrlich

SUMMARY: Cancer known as a malignant tumor, is a class of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. The Ehrlich tumor is a mammary adenocarcinoma of mice developed in solid and ascitic forms. This study was aimed to investigate the effects of paclitaxel on Netrin 1 and Factor 8 expression and also in tumor cell proliferation, apoptosis, angiogenesis, and development of tumor in Ehrlich solid tumors treated with paclitaxel. In this study, 26 adult Balb/C male mice were used. 6 of them were used as stock. Ehrlich ascites cells taken from animals in stock were injected subcutaneously from the neck area to all animals. The mice were randomly assigned to two groups of ten rats per group. Paclitaxel treatment group 10 mg/kg were administered to mice intraperitoneally (i.p.) 4,9, and 14th days. 15th day the animals were sacrificed and tumor tissues were taken. Paraffin-embedded solid tumor sections were stained Hematoxylin & Eosin, Masson's Trichrome. Also solid tumor sections were stained immunohistochemically with Netrin1 and Factor 8. Tunel method was applied to determine apoptosis. Paclitaxel applied as a therapeutic Ehrlich solid tumor reduced the volume of tumors in the treatment groups. At the end of the experiments, in the treatment groups' significantly reduced the Netrin 1 expression and microvessel density compared to the group control. Also paclitaxel in the treatment group increased the number of apoptotic cells. We suggest that decreasing the expression of Netrin 1 would be reduced vessel density and increased apoptosis.

RESUMEN: El cáncer, conocido como tumor maligno, es una clase de enfermedad que involucra un crecimiento celular anormal con potencial de invadir o diseminarse a otras partes del cuerpo. El tumor de Ehrlich es un adenocarcinoma mamario de ratones desarrollado en formas sólidas y ascíticas. Este estudio tuvo como objetivo investigar los efectos del paclitaxel en la expresión de Netrin 1 y Factor 8 y también en la proliferación de células tumorales, apoptosis, angiogénesis y desarrollo de tumores sólidos de Ehrlich tratados con paclitaxel. En esta investigación se utilizaron 26 ratones machos Balb / C adultos. Seis de ellos se utilizaron como stock. Se inyectaron por vía subcutánea células de ascitis de Ehrlich tomadas de animales en la zona del cuello. Los ratones se asignaron aleatoriamente a dos grupos de diez ratas por grupo. Se administraron 10 mg/kg del grupo de tratamiento con paclitaxel a ratones por vía intraperitoneal (i.p.) 4, 9 y 14 días. El día 15 se sacrificaron los animales y se extrajeron los tejidos tumorales. Las secciones de tumor sólido incluidas en parafina se tiñeron con hematoxilina y eosina y tricrómico de Masson. También se tiñeron inmunohisto-químicamente secciones de tumor sólido con Netrin1 y Factor 8. Se aplicó el método Tunel para determinar la apoptosis. El paclitaxel aplicado como tumor sólido terapéutico de Ehrlich redujo el volumen de tumores en los grupos de tratamiento. Al final de los experimentos, en los grupos de tratamiento se redujo significativamente la expresión de Netrin 1 y la densidad de microvasos en comparación con el grupo control. Además, el paclitaxel en el grupo tratamiento aumentó el número de células apoptóticas. Sugerimos que la disminución de la expresión de Netrin 1 reduciría la densidad de los vasos y aumentaría la apoptosis.

Application of vincristine-loaded platelet therapy in three dogs with refractory immune-mediated thrombocytopenia

Three dogs presented with refractory immune-mediated thrombocytopenia (IMT). All patients failed to respond to prednisone, which is considered a mainstay of immunosuppressive therapy. Vincristine-loaded platelets (VLPs), which act selectively on mononuclear phagocytes,were introduced. After the VLPs were transfused, two dogs responded quickly withimproved clinical signs while the third dogwith recurrent IMT was euthanized due to its deteriorating condition. This case report describesthe efficacy of VLP therapy in refractory IMT patients.

Association between perineal trauma and pain in primiparous women / Associación entre el trauma perineal y dolór em primíparas / Associação entre trauma perineal e dor em primíparas

Objective To identify the association between perineal trauma and pain in 473 primiparous women. Method Cross-sectional study in which pain was measured by the numerical pain scale (0 to 10 - 0 being no pain and 10 maximal pain). Results The prevalence and mean intensity of pain were 33.0% and 4.7 points (standard deviation = 2.0) in the numeric scale, respectively. Episiotomy represented the most frequent trauma (46.7%). The occurrence and intensity of the pain were associated with perineal trauma and postpartum time. Having perineal trauma tripled the chance of pain. Each hour elapsed following the birth reduced the chance of pain by 4.8%. Conclusion Primiparous women are subject to a high frequency of perineal trauma, with episiotomy being the most prominent. Perineal pain affects approximately one-third of primiparous women and is associated with the postpartum time and perineal traumas. .

Objetivo Identificar la asociación entre el trauma y el dolor perineal en 473 primíparas. Método Estudio transversal, en el que el dolor se midió por medio de la escala numérica del dolor (0 a 10; 0 = ningún dolor y 10 = dolor máximo). Resultados La prevalencia y el promedio de intensidad del dolor fueron 33,0% y 4,7 (Desviación Estándar = 2,0) puntos en la escala, respectivamente. La episiotomía fue el trauma más frecuente (46,7%). La ocurrencia y la intensidad del dolor se asociaron con el trauma y el tiempo del postparto. Tener trauma perineal triplica la probabilidad de tener dolor. Cada hora transcurrida después del nacimiento reduce la posibilidad de dolor en 4,8%. Conclusión Las primíparas están sujetas a altas tasas de trauma perineal, especialmente episiotomía. El dolor perineal afecta aproximadamente a un tercio de las primíparas y se asocia con el tiempo de postparto y el traumatismo perineal.

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Objetivo Identificar a associação entre trauma perineal e dor em 473 primíparas. Método Estudo transversal, no qual dor foi mensurada por meio da escala numérica de dor (0 a 10 – sendo 0 ausência de dor e 10 dor máxima). A prevalência e a média de intensidade de dor foram 33,0% e 4,7 (Desvio Padrão = 2,0) pontos na escala numérica, respectivamente. Resultados A episiotomia foi o trauma mais frequente (46,7%). A ocorrência e a intensidade da dor foram associadas ao trauma perineal e ao tempo de pós-parto. Ter trauma perineal triplicou a chance de dor. Cada hora decorrida depois do parto reduziu a chance de dor em 4,8%. Conclusão As primíparas estão sujeitas a elevada frequência de trauma perineal, sobretudo episiotomia. A dor perineal afeta, aproximadamente, um terço das primíparas e está associada ao tempo de pós-parto e aos traumas locais. .

Onicólisis exudativa y paroniquia bacteriana aguda en relación con BIBF-1120 y paclitaxel: respuesta a la terapia tópica / Exudative onycholysis and acute bacterial paronychia related to BIBF-1120 and paclitaxel: response to topical therapy

Se presenta el caso de una paciente de 50 años de edad con cáncer de mama tratada con paclitaxel y BIBF 1120 semanal. La paciente desarrolló al final del duodécimo ciclo de quimioterapia una onicólisis distal, con exudado seroso intenso en el hiponiquio, dolor y mal olor en todas las uñas de las manos. Se trató con ácido fusídico tópico y aceponato de metilprednisolona al 1% dos veces al día, con una excelente respuesta desde los tres primeros días de tratamiento. A la semana de iniciar la terapia tópica, se observó una paroniquia bacteriana con la pérdida de la uña del quinto dedo de la mano izquierda, con cultivos positivos para Staphylococcus aureus sensible a meticilina. Hay pocos casos publicados de onicólisis exudativa asociada a quimioterapia. Sin embargo, están especialmente relacionados con paclitaxel. No se observaron recurrencias de las alteraciones ungueales semanas después de culminar la quimioterapia. Los corticoides tópicos y el ácido fusídico podrían ser considerados como una opción terapéutica cuando la onicólisis exudativa relacionada con paclitaxel esté establecida.

A case of a 50 years-old breast cancer patient treated with weekly paclitaxel and BIBF 1120 is reported herein. At the end of the twelfth cycle of chemotherapy, the patient developed distal onycholysis with intense hyponychium serous exudates, pain and malodor in all her fingernails. It was treated with topical fusidic acid and 1% methylprednisolone aceponate two times daily, with an excellent clinical response from the first three days of treatment. Bacterial paronychia with nail plate loss of the fifth left fingernail was observed a week after the topical therapy was started, with positive cultures for Methicillin susceptible Staphylococcus aureus. There are few reported cases of exudative onycholysis associated with chemotherapy. However, these are especially related to paclitaxel. No recurrences of nail disturbances were observed weeks after the end of chemotherapy. Topical corticosteroids and fusidic acid could be considered as a therapeutic option when exudative onycholysis related to paclitaxel is established.

Metformin synergistically enhances antiproliferative effects of cisplatin and etoposide in NCI-H460 human lung cancer cells / Metformina sinergicamente potencializa os efeitos antiproliferativos de cisplatina e etoposideo em linhagem de celulas de cancer humano de pulmao NCI-H460

OBJECTIVE: To test the effectiveness of combining conventional antineoplastic drugs (cisplatin and etoposide) with metformin in the treatment of non-small cell lung cancer in the NCI-H460 cell line, in order to develop new therapeutic options with high efficacy and low toxicity. METHODS: We used the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and calculated the combination index for the drugs studied. RESULTS: We found that the use of metformin as monotherapy reduced the metabolic viability of the cell line studied. Combining metformin with cisplatin or etoposide produced a synergistic effect and was more effective than was the use of cisplatin or etoposide as monotherapy. CONCLUSIONS: Metformin, due to its independent effects on liver kinase B1, had antiproliferative effects on the NCI-H460 cell line. When metformin was combined with cisplatin or etoposide, the cell death rate was even higher. .

OBJETIVO: Testar a eficácia da combinação terapêutica de antineoplásicos convencionais (cisplatina e etoposídeo) com metformina em linhagem celular NCI-H460 de câncer de pulmão não pequenas células, a fim de desenvolver novas possibilidades terapêuticas com eficácia superior e reduzida toxicidade. MÉTODOS: Foi utilizado o ensaio de brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazólio (MTT) e calculado o índice de combinação dos fármacos estudados. RESULTADOS: Observamos que o uso de metformina em monoterapia reduziu a viabilidade celular metabólica da linhagem de células estudada. O uso de metformina em combinação com cisplatina ou etoposídeo foi sinérgico e superior à monoterapia com cisplatina ou etoposídeo. CONCLUSÕES: A metformina, devido às suas ações independentes em liver kinase B1, apresentou atividade antiproliferativa na linhagem NCI-H460 e, em combinação com cisplatina ou etoposídeo, ampliou a taxa de morte celular. .

Quimioterapia neoadjuvante e resposta patológica: coorte retrospectiva / Neoadjuvant chemotherapy and pathologic response: a retrospective cohort

OBJETIVO: Avaliar a taxa de resposta patológica completa atingida pelas pacientes com diagnóstico de câncer de mama localmente avançado submetidas à quimioterapia neoadjuvante baseada no esquema doxorrubicina/ciclofosfamida seguido de paclitaxel. MÉTODOS: Coorte retrospectiva de pacientes admitidas no Hospital de Câncer de Barretos com câncer de mama localmente avançado entre 2006 e 2008 submetidas ao protocolo de doxorrubicina/ciclofosfamida seguido de paclitaxel (4 ciclos de doxorrubicina 60mg/m² e ciclofosfamida 600mg/m² a cada 21 dias; 4 ciclos de paclitaxel 175mg/m² a cada 21 dias). As seguintes variáveis foram avaliadas: idade, menopausa, performance status, estadiamento clínico inicial, dados antropométricos, quimioterapia (dose - duração), perfil de toxicidade, estadiamento clínico pós-tratamento, cirurgia, resposta patológica completa, sobrevida livre de doença e características anatomopatológicas (tipo e grau histológico, perfil hormonal e comprometimento linfonodal). A análise estatística foi realizada considerando-se o nível de significância de 5%. RESULTADOS: Das 434 pacientes avaliadas, 136 foram excluídas por erro no estadiamento ou por terem recebido outro tipo de quimioterapia. A mediana de idade foi 50 anos, todas com performance status 0-1. A mediana do tamanho clínico inicial do tumor foi 65mm e a mediana do tamanho clínico final do tumor foi 22mm. Apresentaram resposta patológica completa 51 (17,1%) pacientes. Aquelas que apresentavam perfil hormonal negativo ou que eram triplo-negativas (Her-2 e perfil hormonal negativos) tiveram impacto favorável na resposta patológica completa. CONCLUSÃO: Quimioterapia neoadjuvante com doxorrubicina/ciclofosfamida seguidas de paclitaxel ofereceu taxa de resposta patológica completa na população estudada de acordo com a literatura. Pacientes triplo-negativas tiveram maior chance de atingir essa resposta.

OBJECTIVE: To evaluate the complete pathologic response attained by patients diagnosed with locally advanced breast cancer submitted to neoadjuvant chemotherapy based on the doxorubicin/cyclophosphamide regimen followed by paclitaxel. METHODS: A retrospective cohort of patients with locally advanced breast cancer, admitted to the Hospital de Câncer de Barretos between 2006 and 2008 submitted to the doxorubicin/cyclophosphamide protocol followed by paclitaxel (4 cycles of doxorubicin 60mg/m² and cyclophosphamide 600mg/m² every 21 days; 4 cycles of paclitaxel 175mg/m² every 21 days). The following variables were assessed: age, menopause, performance status, initial clinical staging, anthropometric data, chemotherapy (dose - duration), toxicity profile, post-treatment staging, surgery, pathologic complete response rate, disease-free survival, and pathological characteristics (type and histological degree, hormonal profile and lymph node involvement). Statistical analysis was performed using a 5% level of significance. RESULTS: Of the 434 patients evaluated, 136 were excluded due to error in staging or because they had received another type of chemotherapy. Median age was 50 years, all with performance status 0-1. Median initial clinical size of tumor was 65mm and the median final clinical size of the tumor was 22mm. Fifty-one (17.1%) patients experienced a pathologic complete response. Those with a negative hormonal profile or who were triple-negative (negative Her-2 and hormonal profile) experienced a favorable impact on the pathologic complete response. CONCLUSION: Neoadjuvant chemotherapy with doxorubicin/cyclophosphamide followed by paclitaxel provided a pathologic complete response in the population studied in accordance with that observed in the literature. Triple-negative patients had a greater chance of attaining this response.

Resveratrol diminishes platelet aggregation and increases susceptibility of K562 tumor cells to natural killer cells.

Platelet aggregation around migrating cancer cells protects them against the activity of natural killer cells (NKCs). The inability of immune system to response results in the progression of malignant diseases. This study was designed to evaluate the effects of resveratrol (3, 4', 5-trihydroxystilbene) on platelet aggregation and NKCs activity. Experiments were designed to evaluate the platelet aggregation, production of thromboxane B2 (TXB2), estimation of expression of the platelet receptor GpIIb/IIIa (major biological markers for platelet aggregation) and functional activity of the NKCs against the K562 cancer cell line after incubation with various concentrations of reveratrol. Resveratrol at a concentration of 3 × 10-3Μ completely inhibited platelet aggregation (p<0.05), decreased TXB2 levels (p<0.05) and inhibited the expression of receptor GpIIb/IIIa in non-stimulated platelets (p<0.05). At the same concentration, it increased the NKCs cytotoxic activity at an average rate of 319 ± 34, 450 ± 34 and 62 ± 2.4% (p<0.05) in the NKC/targets cells ratios of 12.5:1, 25:1 and 50:1, respectively. Thus, resveratrol not only completely inhibited platelet aggregation and reduced TXB2 levels and expression of receptor GpIIb/IIIa, but also increased the cytotoxic activity of NKCs in vitro and thus increased the susceptibility of tumor cells to NKCs. Thus, resveratrol can be used as an additional supplement to modulate the immune system and to inhibit platelet aggregation in thromboembolic episodes. Further clinical investigation in vivo could lead to specific concentrations that may maximize the beneficial effect of resveratrol.

Antitumor function and mechanism of phycoerythrin from Porphyra haitanensis

The anti-tumor effect of R-Phycoerythrin (R-PE) from Porphyra haitanensis was studied using cell line HeLa as an in vitro model and Sarcoma-180 (S180) tumor-bearing mice as an in vivo model. The results showed that the combination treatment of R-PE and photodynamic therapy PDT) significantly inhibited the growth of HeLa cells up to 81.5%, with a fair dose-effect relationship, but did not inhibit endothelial cells. The annexin v-fitc/PI fluorescence staining experiments demonstrated that at doses between 0~60µg/mL, apoptosis cells and later stage apoptosis cells or necrosis cells increased significantly as the R-PE dosage increased. DNA electrophoresis showed that after R-PE+PDT treatment of HeLa cells for 24 hours, a light "smear" band between 100~400bp appeared to indicate the degradation of genomic DNA. The QRT-PCR results showed that R-PE+PDT treatment increased caspase-3 and caspase-10 gene expression and decreased the Bcl-2 gene expression level significantly as the R-PE dose increased, implying that R-PE promoted HeLa cell apoptosis. Compared with untreated S180 tumor-bearing mice, R-PE injection significantly inhibited the growth of S180 in tumor-bearing mice up to 41.3% at a dose of 300mg-kg-1. Simultaneously, the significant increase of superoxide dismutase (SOD) activity in serum (p < 0.01) and the decrease of the malondialdehyde (MDA) level in liver suggests that R-PE improved the anti-oxidant ability of the S180 tumor-bearing mice, which may related to its antitumor effect. In addition, the R-PE caused a significant increase (p < 0.05) in the spleen index and thymus index, and a significant increase (p < 0.01) in lymphocyte proliferation, NK cell kill activity and the TNF-α level in the serum of S180 tumor-bearing mice. These results strongly suggest that the antitumor effect of R-PE from Porphyra haitanensis functioned by increasing the immunity and antioxidant ability of S180 tumor-bearing mice, promoting apoptosis by increasing protease gene expression and TNF-α secretion.

A Prospective, Randomized Comparison of Promus Everolimus-Eluting and TAXUS Liberte Paclitaxel-Eluting Stent Systems in Patients with Coronary Artery Disease Eligible for Percutaneous Coronary Intervention: The PROMISE Study

We aimed comparing two-year clinical outcomes of the Everolimus-Eluting Promus and Paclitaxel-Eluting TAXUS Liberte stents used in routine clinical practice. Patients with objective evidence of ischemia and coronary artery disease eligible for PCI were prospectively randomized to everolimus-eluting stent (EES) or paclitaxel-eluting stent (PES) groups. The primary end-point was ischemia-driven target vessel revascularization (TVR) at 2 yr after intervention, and the secondary end-point was a major adverse cardiac event (MACE), such as death, myocardial infarction (MI), target lesion revascularization (TLR), TVR or stent thrombosis. A total of 850 patients with 1,039 lesions was randomized to the EES (n=425) and PES (n=425) groups. Ischemic-driven TVR at 2 yr was 3.8% in the PES and 1.2% in the EES group (P for non-inferiority=0.021). MACE rates were significantly different; 5.6% in PES and 2.5% in EES (P = 0.027). Rates of MI (0.8% in PES vs 0.2% in EES, P = 0.308), all deaths (1.5% in PES vs 1.2% in EES, P = 0.739) and stent thrombosis (0.3% in PES vs 0.7% in EES, P = 0.325) were similar. The clinical outcomes of EES are superior to PES, mainly due to a reduction in the rate of ischemia-driven TVR.

Use of pyridoxine and pyridostigmine in children with vincristine-induced neuropathy.

Four children with vincristine (VCR)-induced neuropathy are being reported. All cases were followed with the diagnosis of acute lymphoblastic leukemia. Two were boys aged between 2 and 13 year. Electromyographic examination consisted of sensoriomotor polyneuropathy with axonal involvement in three patients. In another patient, it consisted of motor axonal polyneuropathy. In all patients, pyridoxine and pyridostigmine were successfully used in the treatment of VCR-induced neuropathy. They recovered completely with this drug combination. Recovering period of symptoms was between 1-2 week.

Individualized Tumor Response Testing for Prediction of Response to Paclitaxel and Cisplatin Chemotherapy in Patients with Advanced Gastric Cancer

The purpose of our study was to determine the most accurate analytic method to define in vitro chemosensitivity, using clinical response as reference standard in prospective clinical trial, and to assess accuracy of adenosine triphosphate-based chemotherapy response assay (ATP-CRA). Forty-eight patients with chemo-naive, histologically confirmed, locally advanced or metastatic gastric cancer were enrolled for the study and were treated with combination chemotherapy of paclitaxel 175 mg/m2 and cisplatin 75 mg/m2 for maximum of six cycles after obtaining specimen for ATP-CRA. We performed the receiver operator characteristic curve analysis using patient responses by WHO criteria and ATP-CRA results to define the method with the highest accuracy. Median progression free survival was 4.2 months (95% confidence interval [CI]: 3.4-5.0) and median overall survival was 11.8 months (95% CI: 9.7-13.8) for all enrolled patients. Chemosensitivity index method yielded highest accuracy of 77.8% by ROC curve analysis, and the specificity, sensitivity, positive and negative predictive values were 95.7%, 46.2%, 85.7%, and 75.9%. In vitro chemosensitive group showed higher response rate (85.7% vs. 24.1%) (P=0.005) compared to chemoresistant group. ATP-CRA could predict clinical response to paclitaxel and cisplatin chemotherapy with high accuracy in advanced gastric cancer patients. Our study supports the use of ATP-CRA in further validation studies.

Orbital Metastatic Angiosarcoma

We report a case of a 48-year-old man who developed metastatic angiosarcoma in her left orbit. A 48-year-old man was first sent to us for a check up of proptosis of the left eye. A left orbital tumor was recognized on orbital computed tomography scans. The open biopsy showed angiosarcoma. Chest X-ray films and thoracic computed tomography showed an abnormal mass in the left inferior lung field. Angiosarcoma was confirmed by transbronchial lung biopsy. In summary, we believed that the orbital tumour was an initial symptom of the metastasis ensuing from the lung angiosarcoma.

Vincristine delays gastric emptying and gastrointestinal transit of liquid in awake rats

We evaluated the effects of vincristine on the gastrointestinal (GI) motility of awake rats and correlated them with the course of vincristine-induced peripheral neuropathy. Vincristine or saline was injected into the tail vein of male Wistar rats (180-250 g) on alternate days: 50 µg/kg (5 doses, N = 10), 100 µg/kg (2, 3, 4 and 5 doses, N = 49) or 150 µg/kg (1, 2, or 5 doses, N = 37). Weight and stool output were measured daily for each animal. One day after completing the vincristine treatment, the animals were fasted for 24 h, gavage-fed with a test meal and sacrificed 10 min later to measure gastric emptying (GE), GI transit and colon weight. Sensory peripheral neuropathy was evaluated by hot plate testing. Chronic vincristine treatments with total cumulative doses of at least 250 µg/kg significantly decreased GE by 31-59 percent and GI transit by 55-93 percent. The effect of 5 doses of vincristine (150 µg/kg) on GE did not persist for more than 1 week. Colon weight increased after 2 and 5 doses of vincristine (150 µg/kg). Fecal output decreased up to 48 h after the fifth dose of vincristine (150 µg/kg). Vincristine decreased the heat pain threshold 1 day after 5 doses of 50-100 µg/kg or after 3-5 doses of 150 µg/kg. This effect lasted for at least 2 weeks after the fifth dose. Chronic intravenous vincristine treatment delayed GE and GI transit of liquid. This effect correlated with the peak increase in colon weight but not with the pain threshold changes.

A comparative study of low dose weekly paclitaxel versus cisplatin with concurrent radiation in the treatment of locally advanced head and neck cancers.

PURPOSE: The purpose of this study was to compare low dose weekly paclitaxel versus cisplatin with concurrent radiation in locally advanced head and neck cancers. MATERIALS AND METHODS: From August 2005 to July 2006, a total of 100 biopsy proven, locally advanced head and neck cancers were enrolled for the study. All the patients were stratified in two groups, study group A and control group B. Study group patients received injection Paclitaxel 20 mg/m 2 , I/V 1 hr infusion weekly for 6 weeks and control group patients received injection Cisplatin 30 mg/m 2 , I/V 2 hrs infusion weekly for 6 weeks. All patients received 66-70 Gy concurrent radiation at the rate of 2 Gy/day, 5 #/week, in 6-7 weeks by cobalt theratron phoenix - 80 teletherapy units. RESULT: Complete response achieved in 73% of patients in study group and 64% of patients in control group. There was no statistically significant difference observed between the study group and the control group (chi2 = 1.167, df = 1, level of significance 0.05). On 3-10 months of follow-up 59% of patients in the study group and 42% of patients in the control group are alive and disease free. Local toxicities including mucositis, dysphasia and skin reactions were more in the study group but tolerable. CONCLUSION: Efficacy of paclitaxel in low dose weekly schedule is comparable to cisplatin in locally advanced head and neck squamous cell carcinoma. Further analysis and follow-up are needed to evaluate if this benefit will translate into prolonged survival.

Highly elevated serum CA 125 in a lady with ascites and retroperitoneal mass--a diagnostic dilemma.

BACKGROUND: Cancer antigen 125 (CA 125), a widely used tumor marker for monitoring epithelial ovarian cancer, is also found to be raised in non-gynecological tumors and non malignant disease involving peritoneum. We report a case of non-Hodgkin's lymphoma who presented with peritoneal and pleural effusions with a very high level of serum CA 125. CASE: Fifty four years female presented with gross ascitis, bilateral moderate pleural effusions, right retroperitoneal mass and a very high serum CA 125 level (4462.60 u/ml). She was initially evaluated to rule out ovarian malignancy but her biopsy from retroperitoneal mass came out to be diffuse large B cell non-Hodgkin's lymphoma. CONCLUSION: In a female patient with ascitis with high serum CA 125 level, a differential diagnosis of lymphoma should not be overlooked unless cytology comes positive for epithelial carcinoma cells.

Trombose coronariana tardia secundária a implante de stent com paclitaxel sem reestenose dos stents convencionais / Late coronary thrombosis secondary to implantation of paclitaxel-eluting stent without restenosis of conventional stents

Homem de 39 anos com angina pós-infarto. Coronariografia demonstrou: obstrução total proximal da artéria coronária direita (ACD), lesões obstrutivas de 95 por cento na artéria descendente anterior (ADA), 80 por cento no 2° ramo marginal esquerdo (ME) e 95 por cento na artéria circunflexa (ACX). O paciente foi submetido a implante de stent TAXUS 3,0 x 24 mm e stent EXPRESS 2,75 x 24 mm nos terços proximal e distal da ACD, respectivamente, e stent INFINNIUM 3,0 x 24 mm na ADA com sucesso. Após 7 meses, apresentou IAM anterior por trombose do stent INFINNIUM e reestenose do stent TAXUS, sem perda de resultado nos stents convencionais.

A male 39 year-old patient with post-infarction angina. The coronary angiography showed total proximal obstruction of right coronary artery (RCA), obstructive lesions of 95 percent of the anterior descending artery (ADA), 80 percent of the second left marginal branch (LM2), and 95 percent of the circumflex artery (CXA). The patient was successfully implanted with a Taxus 3.0 x 24 mm stent and an Express 2.75 x 24 mm stent in the proximal and distal thirds of the RCA, respectively, and with an Infinnium 3.0 x 24 mm stent in the ADA. After seven months, the patient had an anterior acute myocardial infarct (AMI) due to thrombosis of the Infinnium stent and restenosis of the Taxus stent, with no loss of results in the conventional stents.

Cobalt chromium stent with antiproliferative for restenosis trial in India (COSTAR I).

BACKGROUND: The CoStar stent is a novel cobalt chromium stent designed specifically for drug delivery. The COSTAR I trial represents the first-in-man study of the CoStar Paclitaxel-Eluting Coronary Stent System evaluating three dose release formulations of paclitaxel in a bioresorbable polymer matrix in the treatment of de novo coronary lesions. METHODS: The COSTAR I Trial was a prospective, multi-center registry enrolling 87 patients in four Indian centers for treatment of up to two de novo lesions = 25 mm in length in a reference vessel 2.5-3.5 mm in diameter. Three dose release formulations were studied: 30 microg eluted over 10 days bidirectionally (Group 1, n =10), 10 microg eluted over 30 days abluminally (Group 2, n=40) and 3 microg eluted over 30 days abluminally (Group 3, n = 37). RESULTS: Demographics and lesion characteristics were similar between the groups and treatment in all three groups included small caliber vessels (RVD 2.45 +/- 0.30 - 2.57 +/- 0.36 mm). The primary endpoint of in-stent late loss at four months was lowest in Group 2 (0.43 +/- 0.43 mm) compared to Group 1 and Group 3 (0.51 +/- 7 mn; 0.74 mm and 1.07 +/- 0.65 mm respectively). In-segment late loss followed similar trends, being lowest in Group 2 (0.24 +/- 0.39 mm) compared to Groups 1 and 3 (0.52 +/- 0.66 mm and 0.76 +/- 0.57 mm respectively). Group 2 demonstrated better angiographic out-comes at 12 months with in-stent late loss of 0.55 +/- 0.38 mm when compared to Groups 1 and 3 (0.90 +/- 0.76 mm and 0.74 +/- 0.55 mm respectively). Cumulative binary restenosis rates at twelve months were 1.9%, 35.7% and 39.1% in Groups 2, 1 and 3 respectively. Clinical outcomes trended similarly with cumulative MACE rates at twelve months being lowest at 7.5% in Group 2 as compared to 20% in Group 1 and 21.6% in Group 3 respectively. CONCLUSIONS: In this first-in-man feasibility trial, angiographic and clinical results seen with the extended release formulation at a higher dose (10 microg/30 days) demonstrate the feasibility of the CoStar stent platform in the treatment of native coronary lesions. It also demonstrates the importance of drug dose and release kinetics.

Primary endobronchial anaplastic large cell lymphoma in a pediatric patient

The authors describe a pediatric patient who presented with a 3-month history of dry cough, chest pain, progressive breathlessness, fever and recurrent pneumonia with atelectasis. A fiberoptic bronchoscopy revealed a whitish lesion at the left bronchus. A biopsy of the lesion demonstrated an anaplastic large cell lymphoma (ALCL). Evaluation for disseminated disease was negative. After the patient completed chemotherapy the lesion abated and she has been in complete remission for almost 4 years. Although extranodal involvement of ALCL is frequent at some stage of the disease, endobronchial involvement is extremely rare even in the presence of advanced disease. To our knowledge, this is the first primary isolated endobronchial ALCL described in a pediatric patient.