Role of N-acetyl cysteine on bone marrow-derived hematopoietic stem/progenitor cell cryopreservation: Outcome on the oxidative stress-mediated cryodamage and repopulation Capacity into hematopoietic lineages

Cryopreservation of hematopoietic stem/progenitor cells (HSPCs) is associated with oxidative stress-mediatedcryodamage, hence compromising the therapeutic potency. The roles of N-acetyl cysteine (NAC) on the oxidativestress-mediated cryodamage and repopulation capacity of HSPCs into myeloid, erythroid, and pre-B lymphoidprogenitors were investigated. Mice bone marrow-derived HSPCs were cultured for 24 hours, followed bycryopreservation at 1 × 106/ml cells in cryomedium containing 10% dimethyl sulfoxide with NAC (0.25, 0.5, or 2.0µM) or without for 48 hours, 2 weeks, and 4 weeks at −80°C. Cryopreservation significantly reduced cell viability atpost-thawed (p < 0.05) with long-term cryopreservation conferred a greater cell recovery. NAC improved the bonemarrow-derived HSPC viability (p < 0.05) at 0.5 and 2.0 µM after 48 hours of cryopreservation. Cryopreservationlowered the malondialdehyde level (p < 0.05) although glutathione, superoxide dismutase, and protein carbonyl levelswere not significantly affected. Repopulation capacity of HSPCs into myeloid–erythroid progenitors was greatlyreduced (p < 0.05) after 4 weeks of cryopreservation as compared to precryopreservation group. Meanwhile, NACsupplementation showed no remarkable effect on oxidative stress-mediated cryodamage and repopulation capacity ofHSPCs. Conclusively, the cryoprotective role of NAC on the cryopreservation of HSPCs deserves further investigation

Treatment of Locally Advanced Squamous Cell Carcinoma of Head and Neck with Hybrid Accelerated Radiotherapy and Concurrent Chemotherapy

Introduction: Head and neck cancer is the most common cancer in India. Overall, 57.5% of global head and neck cancersoccur in Asia, especially in India. Even though anatomical subsites of head and neck regions are accessible to clinicalexamination, 60–80% of patients in India report with locally advanced disease in comparison with developed countries whichis 40% only.Concurrent chemoradiation remains the standard treatment approach in locally advanced head and neck cancers.Conventional radiation schemes with 3 weekly cisplatin produce a response rate of 50–60% only in locally advanced head andneck cancer. Studies reveal that tumor clonogen repopulation might be one of the most important factors determining treatmentoutcome. Various retrospective studies and clinical trials have shown that an increase in tumor control can be achieved byshortening treatment time using altered fractionation schemas.Aim: In this present work, we made an attempt to improve the therapeutic ratio by hyperfractionation and accelerated radiationregimens.Methods: To achieve the above, 30 patients of locally advanced squamous cell carcinoma with different disease status werechosen. Patients subjected to hybrid accelerated radiotherapy with total dose of 72 Gy along with cisplatin 100 mg/m2 were givenon day 1 and day 22. Complete response rate in primary T2, T3, and T4 tumors is 100%, 86.95%, and 16.67%, respectively.Results: Complete response rates attained by N0, N1, and N2 nodes are 100%, 100%, and 50%, respectively. 16.6% hadGrade 2 mucositis and 50% had Grade 3 mucositis. 80% had Grade 3 and 20% had Grade 2 skin toxicities. No Grades 3 and4 hematological toxicities such as anemia, leucopenia, or thrombocytopenia were observed.Conclusion: Hence, we suggest that combination of hybrid accelerated radiotherapy and cisplatin mono-chemotherapy, withmanageable, although substantial, toxicity as an effective alternative regimen to treat head and neck cancer

The 4Rs in radiation therapy / 中华放射医学与防护杂志

It has been realized that the 4Rs (repair,repopulation,redistribution,and reoxygenation) would affect the result of cell irradiation,and thus radiation treatment.The 4Rs each occurs at different dose rates,usually very low dose rates.Depending on the dose rate used for treatment,the corresponding R should be included in the linear-quadratic equation (LQ) and biological effective dose (BED) calculation.For low dose rate brachytherapy(LDR) especially permanent implant,all the 4Rs should be included in LQ for BED calculation.The 4Rs,especially repair and repopulation,play a critical role in dose fractionation.Various dose fractionation schemes such as hyperfractionation and hypofractionation are determined in consideration of the 4Rs.Stereotactic radiation therapy uses hypofractionation with high fractional doses and combine with high accuracy target localization techniques to achieve high local control rates compared to conventional dose fractionation schemes.The 4Rs have been taken into account for LDR and permanent implant.Recently,LQ for permanent implant brachytherapy has been modified to include all the 4Rs for gynecological malignancy 131Cs permanent implants.Including the 4Rs in radiation therapy has significantly improved the effectiveness and efficiency of radiation therapy for cancer treatment.

An external tag for fish: tagging effects in different fish size classes and its influence on growth performance and hematology of Lophiosilurus alexandri (Siluriformes: Pseudopimelodidae)

This study tested an external tag for juveniles of Lophiosilurus alexandri and measured the effects of tagging in different size classes of fishes. Experiment 1 evaluated the retention rate and influence of the tag on survival and growth of three hundred fishes divided Small, Medium and Large size classes. After 90 days of experiment the fishes had 100% survival and the tag had a higher retention rate for animals of the Large size class. Experiment 2 evaluated the tag's influence on hematology parameters of forty-two fishes at 5, 10 and 30 days post-tagging. In this experiment both tagged and untagged animals experienced 9.4% mortality. The hematocrit was higher on the 30th day for tagged animals than for untagged animals. No difference was observed for leukocytes, plasma protein, erythrocytes and mean corpuscular volume. It was concluded from Experiment 1 that the tag reduced growth performance when applied to small sized juvenile L. alexandri, and that the tag retention rate increased with increasing animal size. Among the hematological parameters studied for juveniles on the Experiment 2 the tag only influenced the hematocrit parameters, which shows that the tag can be used without considerable influence on the hematological parameters of juvenile L. alexandri.(AU)

Esse estudo testou a utilização de marcadores externos em juvenis de Lophiosilurus alexandri, assim como o tamanho mínimo ideal do peixe para marcação. No experimento 1 foi avaliado a taxa de retenção e a influência do marcador sobre a sobrevivência e crescimento dos peixes divididos por tamanho nas classes: Pequeno, Médio e Grande. Após 90 dias, os peixes apresentaram 100% de sobrevivência e uma taxa de retenção mais elevada para os animais classificados como grandes. O segundo experimento avaliou a influência do marcador sobre os parâmetros hematológicos dos animais após 5, 10 e 30 dias da marcação. Neste experimento, foram observados valores mais elevados para o hematócrito no 30º dia para os animais marcados, enquanto nenhuma diferença foi observada para leucócitos, proteína plasmática, eritrócitos e volume corpuscular médio. Concluiu-se o que o marcador reduziu a taxa de crescimento dos animais menores, e que a taxa de retenção aumentou com o aumento do tamanho do animal. Dos parâmetros hematológicos avaliados, o marcador influenciou apenas no valor do hematócrito, o que mostra que o marcador pode ser usado sem considerável influência nos parâmetros hematológicos do L. alexandri.(AU)

Advances in prostaglandin E2 reprogramming pancreatic cancer microenvironment / 上海交通大学学报（医学版）

Pancreatic cancer is a highly malignant disease with poor prognosis. Accumulating evidences indicate that prostaglandin E2 (PGE2) can promote cancer progression by reprogramming tumor microenvironment (TME). On one hand, PGE2 can regulate immune cells, tumor cells, cancer-associated fibroblasts and endothelial cells in TME to boost growth, invasion and metastasis of pancreatic cancer. On the other hand, exosomes from tumor cells influence the synthesis, release and uptake of PGE2 and enhance its reprogramming abilities. Furthermore, PGE2 even plays an important role in the development of therapy resistance by stimulating tumor repopulation and inducing epithelial-mesenchymal transition. Hence, PGE2 might be a potential therapeutic target for intervention of pancreatic cancer.

Platelet activating factor receptor antagonists improve the efficacy of experimental chemo- and radiotherapy

Platelet activating factor is a lipid mediator of inflammation, and in recent decades, it has emerged as an important factor in tumor outcomes. Platelet activating factor acts by specific binding to its receptor, which is present in both tumor cells and cells that infiltrate tumors. Pro-tumorigenic effects of platelet activating factor receptor in tumors includes promotion of tumor cell proliferation, production of survival signals, migration of vascular cells and formation of new vessels and stimulation of dendritic cells and macrophages suppressor phenotype. In experimental models, blocking of platelet activating factor receptor reduced tumor growth and increased animal survival. During chemotherapy and radiotherapy, tumor cells that survive treatment undergo accelerated proliferation, a phenomenon known as tumor cell repopulation. Work from our group and others showed that these treatments induce overproduction of platelet activating factor-like molecules and increase expression of its receptor in tumor cells. In this scenario, antagonists of platelet activating factor markedly reduced tumor repopulation. Here, we note that combining chemo- and radiotherapy with platelet activating factor antagonists could be a promising strategy for cancer treatment.

Eugenol como anestésico para el manejo de juveniles de Pavón (Cichla orinocensis)

Con el objeto de establecer una concentración anestésica de eugenol óptima para una adecuada manipulación de juveniles de Pavón (Cichla orinocensis), 24 juveniles (57,65 ± 43 g y 16.44 ± 1,17 cm de longitud estándar) provenientes de la estación Piscícola Experimental Casa Piedra de la Fundación Orinoquia de Puerto Carreño, Vichada, Colombia, fueron sometidos a diferentes concentraciones de eugenol (30, 40 y 50 mg/L) y un grupo control. Se presentaron diferencias estadísticamente significativas entre los tratamientos tanto para los tiempos de inducción como de recuperación con las concentraciones de 20, 30 y 50 mg/L (p<0,05), siendo el tratamiento de 20 mg/L el que presento el mayor tiempo de inducción (133±63,21 segundos) y el tratamiento de 50 mg/L presento el menor tiempo de inducción (46±17,51 segundos), los tiempos de recuperación del experimento aumentaron conforme aumentaban las concentraciones anestésicas empleadas, se observaron diferencias significativas (p<0,05) entre los tiempos de recuperación de cada tratamiento. La concentración anestésica de eugenol recomendada para juveniles de pavón (C. orinocensis) obtenida en este trabajo es de 35 mg/L.

In order to establish an optimal concentration of anesthetic eugenol for proper handling of juvenile Pavon (Cichla orinocensis), 24 juveniles (43 ± 57.65 g and 16.44 ± 1.17 cm standard length) from the station Experimental Fish Foundation Orinoquia, Stone House of Puerto Carreño, Vichada, Colombia, were subjected to different concentrations of eugenol (30, 40 and 50 mg / L) and a control group. Statistically significant differences between treatments, for induction times and recovery time with concentrations of 20, 30 and 50 mg / L (p <0.05) were presented. Is the treatment of 20 mg / L which Eugenol como anestésico para el manejo de juveniles de Pavón (Cichla orinocensis) 31 had the highest induction time (133 ± 63.21 seconds) and the treatment of 50 mg / L had the lowest induction time (46 ± 17.51 seconds), the recovery times of the experiment increased proportionally anesthetic concentrations employed, were observed significant differences (p <0.05) between recovery times each treatment. The anesthetic concentration of eugenol recommended for juvenile pavón (C. orinocensis) obtained in this study is 35 mg / L.

A fim de estabelecer uma melhor concentração de eugenol anestésico para tratamento adequado dos juvenis Pavon (Cichla orinocensis), 24 jovens (43 ± 57,65 g e 16,44 ± 1,17 cm de comprimento padrão) da estação Experimental Fish House de pedra em Fundação Orinoquia de Puerto Carreño, Vichada, Colômbia, foram submetidos a diferentes concentrações de eugenol (30, 40 e 50 mg / L) e um grupo controle. -Se diferenças estatisticamente significativas entre os tratamentos para ambos os tempos de indução e recuperação com concentrações de 20, 30 e 50 mg / L (p <0,05) foram apresentados, é o tratamento com 20 mg / L, que teve a mais alta tempo de indução (133 ± 63,21 segundos) e o tratamento de 50 mg / L tiveram o tempo menor de indução (46 ± 17,51 segundos), o tempo de recuperação do experimento aumentou proporcionalmente concentrações anestésicas empregadas, foram observados diferenças significativas (p <0,05) entre os tempos de recuperação de cada tratamento. A concentração do anestésico de eugenol recomendado para Pavón juvenil (C. orinocensis) obtida neste estudo é de 35 mg / L.

Crecimiento y mejora del índice gonadal en el cultivo del erizo de mar Paracentrotus lividus (Echinoida: Echinidae) en Galicia (España) / Growth rate and gonadal index improvement in sea urchin culture Paracentrotus lividus (Echinoida: Echinidae)

Resumen La gran demanda de Paracentrotus lividus (Lamarck, 1816) en países como Francia, Italia, Turquía, Bélgica o Japón, ha elevado el nivel de extracción de este equinodermo en los últimos años que ha generado un desgaste en las poblaciones de erizos, los cuales tardan años en regenerarse. La importancia económica de P. lividus en Galicia, con una producción media anual de 700 000 kg y un valor cercano a los 2 millones de € en el año 2013, nos ha llevado a realizar diversas experiencias con el objetivo de analizar las posibilidades del cultivo en Galicia de esta especie en batea. Se han diseñado tres experiencias: 1) Efecto de cinco dietas y tres densidades sobre el crecimiento de juveniles de P. lividus obtenidos del medio natural; (2) Crecimiento de juveniles de P. lividus obtenidos en criadero, alimentados con algas, y 3) Efecto de diferentes dietas experimentales sobre el índice gonadal de P. lividus de tamaño comercial. Las experiencias se realizaron en una batea de la USC situada en la ría de Muros-Noia (Galicia), durante cuatro años (2007 - 2010), utilizando 2 231 erizos en total, procedentes del medio natural (450), de criadero (773) y de tamaño comercial (1 008), diseñándose diversas dietas experimentales que tratan de incrementar el crecimiento somático y gonadal de los erizos, con el fin de reducir el tiempo de crecimiento de los juveniles procedentes del medio natural y de criadero hasta que alcancen la talla comercial (55 mm de diámetro), o bien hasta que consigan un tamaño adecuado para repoblar las zonas sobreexplotadas del medio natural (20 mm de diámetro), así como el crecimiento de las gónadas de erizos comerciales con diferentes dietas. Mensualmente se tomó el diámetro de los erizos juveniles con el fin de determinar el efecto de las diferentes dietas y densidades sobre el crecimiento de los mismos, así como la determinación del índice gonadal (IG) en los erizos de tamaño comercial para ver el efecto de las diferentes dietas ensayadas. Con los datos obtenidos estimamos que, en la actualidad, no sería rentable alimentar erizos juveniles de P. lividus en batea hasta alcanzar la talla comercial, debido al bajo precio que tiene esta especie en el mercado (3€ / kg aproximadamente), aunque sí sería interesante mantenerlos en cultivo en batea hasta que alcancen el tamaño óptimo para repoblar zonas donde las poblaciones naturales están mermadas, combinando esto con el engorde de gónadas con alguno de los piensos diseñados que aumenta el IG y amplía el tiempo de explotación comercial de los erizos.

Abstract The high demand for Paracentrotus lividus (Lamarck, 1816) in countries like France, Italy, Turkey, Belgium and Japan, has raised the level of extraction of this echinoderm in recent years and has generated wear urchin populations, which take years to regenerate. The economic importance of P. lividus in Galicia, with an average annual production of 700≤000 kg and a value close to € 2 million in 2013, has led us to perform a variety of experiences in order to analyze the possibilities of the culture of this species in Galicia in raft. We have designed three experiences: 1) Effect of five diets and three densities on the growth of juvenile P. lividus obtained from the natural environment; 2) Growth of juvenile P. lividus obtained from hatchery, fed algae, and 3) Effect of different experimental diets on gonadal index of P. lividus commercial size. The experiments were performed on a USC raft situated in the estuary of Muros-Noia (Galicia) for four years (2007 - 2010), using 2 231 total urchins, from the natural environment (450), hatchery (773) and market size (1 008), being designed various experimental diets that try to increase somatic and gonadal growth in sea urchins, in order to reduce the rise time of juveniles from the wild and hatchery until they reach the size commercial (55 mm diameter), or until they get a suitable size to repopulate overfished areas of the natural environment (20 mm diameter), and the growth of the gonads of sea urchins with different diets. Monthly has taken diameter of juvenile sea urchins in order to determine the effect of different diets on growth and densities of the same, as well as determining the gonadal index (GI) in sea urchins of commercial size to see the effect took different tested diets. With the data obtained estimates that, at present, it would be profitable to feed juvenile sea urchins P. lividus in raft to reach commercial size, due to the low price of this species in the market (3€ / kg). Additonally they could reach optimum size and be used to repopulate areas where natural populations are depleted. This should be combined with the fattening of gonads and extended time of commercial exploitation. Rev. Biol. Trop. 63 (Suppl. 2): 261-272. Epub 2015 June 01.

Inhibition of polypeptide extract from scorpion venom on repopulation in Lewis lung adenocarcinoma during chemotherapy / 中草药

Objective: To identify the repopulation in metastatic Lewis lung adenocarcinoma during 5-Fu chemotherapy and observe the inhibition of polypeptide extract from scorpion venom (PESV) on the repopulation. Methods: To make repopulation model, Lewis cells were iv injected into caudal vein of C57BL/6 mice, the mice were ip injected by 5-Fu once every 7 d since day 7 and intervened by ig administration of PESV. Groups were treated differently. Six mice were sacrificed every 7 d, with counting metastatic foci in lung and detecting the level of proliferating cell nuclear antigen (PCNA), vascular endothelial growth factor (VEGF), and microvessel dentity (MVD) expression in Lewis lung metastatic loci by using immunohistochemistry. Results: In model groups, from day 21 to day 28 the numbers of metastatic big loci increased 2.5 averagely, while from day 14 to day 21 increased 0.8 only; The weight of lung from day 21 to day 28 increased more than that from day 14 to day 21; The expression of PCNA was the lowest in day 21, the highest in day 28, and there was no significant difference between day 28 and day 14; The expression in both high- and low-dose PESV groups in day 28 was lower than that in model group. There was a significant effect in high-dose PESV group. In model group the expression of VEGF in day 28 was upregulated significantly (P<0.01 vs that in model group in day 21). Compared with model group, VEGF expression in high-dose PESV group in day 21 and day 28 was downregulated, especially in day 28 (P<0.01). In low-dose PESV group only in day 28 the difference was found (P<0.05 vs that in model group); The change of MVD was the same as PCNA. The expression was the lowest in day 21, the highest in day 28, and there was no significant difference between day 28 and day 14. While in high-dose PESV group, the number of MVD in day 14 was more than that in day 21, and in day 21 more than in day 28, there were significant differences. In low-dose PESV group, in day 14 more than in day 21, but no significant difference was found between day 21 and day 28. Conclusion: The phenomenon of repopulation acceleration is found in Lewis lung adenocarcinoma during 5-Fu treatment and PESV could inhibit the repopulation through anti-angiogenesis which may be one of the mechanisms of inhibiting tumor cell repopulation.

Application of Fah knockout mice in the hepatocyte transplantation and the pathological changes / 中国药科大学学报

Aim: To investigate the pathological changes in NTBC[2-(2-nitro-4-trifluoro-methyl-benzoyl) -1,3 cy-clohexanedione]-induced hepatic injury in mice and in the repopulation of adult hepatocytes in Fah~(-/-) mouse. Methods: Autogenous hepatic injuries in Fah~(-/-) mice were induced by the treatment of NTBC. Injection of hepatocytes obtained from wild-type mice to spleen were transplanted into the Fah~(-/-) mice. Then, changes to body weight and the likelihood of the transplanted Fah~(-/-) mice, and hepatic immunohistochemistry were ob-served. In addition, pathological changes to liver damage induced by NTBC treatment were analyzed under HE-staining microscopy and electron microscopy. Results: The surviving Fah~(-/-) mice subjected to hepatocyte trans-plantation were found to be healthy and in stable body weight. liver repopulation reached to 90% in the 8th week. Repopulating hepatocytes caused no alteration to histological structure of the recipient liver, and subacute hepatic injury occurred in the Fah~(-/-) mice after NTBC treatment. Electronic microscopy observations indicated that necrosis in the hepatocytes occurred at early stage and that apoptosis gradually appeared. It was also shown both necrosis and apoptosis co-existed in the same samples of interest at the following stages of the induced liver injury. Conclusion: Transplanted hepatocytes proliferated in Fah~(-/-) mice allow 90% of the hepatocytic repopula- tion. Repopulation renders normal hepatic function and structure in the recipient Fah~(-/-) mice, as a model of liver repopulation, could be applicable in study of stem cell derived hepatic cells in transplantation assay.

DYNAMIC CHECK OF CERVICAL CARCINOMA BRACHYTHERAPY DOSE AND TUMOR CELL REPOULATION / 肿瘤研究与临床

Objective:To explore the relationship between the accelerated repopulation of tumor cells in the afterloading fractionated radiation therapy and the radiation dose,Ki67 antigen,PcNA & mutation p53 antigen expression were analyzed by continual biopsy on the same patients of cervical carcinoma two weeks (10 Gy)and four weeks(20 Gy).Methods:Ki67 antigen expression and cell cycle analysis (SPF,PI,DEN) were checked by flow cytometry,PCEA & mutation p53 antigen expression were checked by means of immunohistochemical technique and computerized image cytometry.All these indexes were viewed on their relationship with the irradiation dose.Rusults:Ki67 antigen expression and DEN were increased as radiation dose increased.The difference of Ki67,PCNA and mtP53 antigen expression at the dose of 10 Gy had statistical significance compared with before brachytherapy,but it had no statistical significance compared with at the dose of 20 Gy.Conclusion:It may be concluded that the tumor cell repopulation had occurred at the dose of 10 Gy (two weeks after brachytherapy).But these markers were not obviously changed compared with at the dose of 20 Gy,so it leads to a conclusion that tumor cell repopulation was stable.It also offers the theory basis to select the opportunity of accelerated brachytherapy of cervical carcinoma.

Expression of stem cell factor of testes was effected by cytoxan / 重庆医科大学学报

0.05).(4) Repopulation index of experimental groups in 4w were significantly lower than that of control groups(P