Long-term influence of adjuvant therapy on natural killer cell activity in breast cancer

Summary Unstimulated IFN- and IL2-stimulated (NK) cell activities were investigated in patients with breast cancer who had received either local radiotherapy alone or adjuvant chemotherapeutic treatment with CMF combined with radiotherapy 12 to 18 months previously. When tested against the primarily NK-sensitive K562 cell line, patients who had received adjuvant chemotherapeutic treatment with CMF were shown to have a significantly decreased unstimulated and IFN-stimulated NK cell activity, as compared to both patients after radiotherapy only (P<0.002) and P<0.005, respectively) and healthy control persons (P<0.05). The former group of patients also had a significantly decreased IFN-stimulated NK cell activity, when tested against the primarily NK-insensitive Chang hepatoma cell line, as compared to patients after radiotherapy only (P<0.005) and healthy controls (P<0.05). Moreover, patients after radiotherapy only proved to have a significantly increased unstimulated (P<0.01) and IFN-stimulated NK cell activity (K562: P<0.05; Chang hepatoma cell line: P<0.05), as compared to healthy control individuals. In contrast, no difference in IL2-stimulated NK cell activity was detected. The investigation for the expression of CD3 and/or Leu 19 antigens as phenotypic markers of cells with non-MHC restricted cytotoxicity showed a significantly lower percentage of cells with the CD3+ phenotype in patients with breast cancer, irrespective of the chosen post-operative treatment, as compared to healthy controls (P<0.01). Finally, patients with breast cancer who had received radiotherapy only had a significant trend towards an increased percentage of CD³+/Leu 19+ PMNC, as compared to both patients after CMF treatment (P<0.05) and healthy controls (P<0.025). We conclude that patients with breast cancer vary on a long-term basis in their NK activity and in the phenotype of their PMNC depending on their post-operative adjuvant management.Abbreviations NK natural killer cells - IFN interferon - IL 2 interleukin 2 - CMF cyclophosphamide, methotrexate, fluorouracil - ER oestrogen receptor - PMNC peripheral blood mononuclear cells - MHC major histocompatibility complex - CTL cytotoxic T lymphocytes     

The Effect of Phosphinothricin (Glufosinate) on Glutathione Synthesis in Plants

The inhibitory effect of DL-phosphinothricin (glufosinate) on glutathione synthesis was studied in vivo and in vitro. The influence of phosphinothricin on γ-glutamylcysteine synthetase was compared with the already known effects of l -buthionine sulfoximine and l -methionine sulfoximine. The results showed that phosphinothricin and buthionine sulfoximine are inhibitors of γ-glutamylcysteine synthetase of plants. With both substances the enzyme was inhibited by 50 % at a concentration of 7 . 10^?4M (pI₅₀ = 3.15). Methionine sulfoximine reduced the enzyme activity by 50% at 5 . 10^?2 M (pI₅₀ = 1.30). It is discussed that the target enzyme of phosphinothricin is the glutamine synthetase whereas the γ-glutamylcysteine synthetase is only an accessory target.     

In vivo modulation of natural killer cell activity by tamoxifen in patients with bilateral primary breast cancer

Natural killer (NK) cell activity, the autologous mixed lymphocyte reaction (AMLR) and proportions of T cell subpopulations (CD3⁺/CD4⁺ and CD3⁺/CD8⁺) and NK cells (CD16⁺) were studied in 21 patients with bilateral primary breast cancer (BBC), 10 patients with single-breast cancer (SBC) and 20 healthy controls. All patients studied had no evidence of disease and had been off radiotherapy and/or chemotherapy for at least 1 year. Ten patients with BBC were also treated with tamoxifen. Patients with SBC had NK cell activity, AMLR responses and T cell subpopulations that were comparable to those of normal controls. In patients with BBC, a significant (P<0.01) increase in NK activity compared to that in normal controls (42±13% versus 21±10%, effector-to-target cell ratio, 251) and a significant (P<0.05) decrease in CD4⁺ T cell proportions (30±15% versus 49±13%) and absolute numbers (472±82/mm³ versus 953±131/mm³) were found. However, the proliferative response of BBC patients' T lymphocytes in AMLR was in the range of the normal controls. Lymphocytes derived from 10 BBC patients treated with tamoxifen exhibited NK cell activity that was comparable to that of normal controls and patients with SBC, and was significantly (P<0.01) reduced compared to the pretreatment period. BBC patients who received tamoxifen also show a reduction in the proportion of CD4⁺ T cells and in AMLR proliferative responses, which decreased compared to levels in normal controls. Taken together, these results indicate that long-term tamoxifen treatment modulates immune responses in BBC patients.     

A Randomized Controlled Trial of Conventional Fraction and Late Course Accelerated Hyperfraction Three-Dimensional Conformal Radiotherapy for Esophageal Cancer

We compared the curative and side-effects in esophageal carcinoma treated by conventional fraction (CF) and late course accelerated hyperfraction (LCAF) three-dimensional conformal radiotherapy. Ninety-eight patients were randomly assigned to two different radiotherapy model groups. Fifty patients were treated using CF three-dimensional conformal radiotherapy at a total dose of 60–68 Gy; 2 Gy/F; 5 fractions/week (median 64 Gy), 48 patients were treated with LCAF (First CF-treated at the dose 40 Gy. Later, LCAF-treated 1.5 Gy/F; 2 fractions/day; 21–27 Gy; a total dose of 61–67 Gy; median 64 Gy). The data showed that the 1-, 2- and 3-year-survival rates in LCAF group were 79.2, 56.3, and 43.8%, compared to 74, 54, and 36% in CF group (P = 0.476). The 1-, 2- and 3-year-local control rates in LCAF group were 81.3, 62.5, and 50%, compared to 78, 58, and 42% in CF group (P = 0.454). In CF group, the incidence of radiation-induced esophagitis was lower than that in LCAF group (72 vs. 93.8%; P = 0.008) and there was no significant difference between rates of radiation-induced pneumonitis in CF and LCAF groups (10 vs. 6.25%; P = 0.498). It was concluded that the 1-, 2- and 3-year-local control and survival rates of esophageal carcinoma patients treated with LCAF were slightly better than CF radiotherapy; however, the radiation side-effects in LCAF group were greater than those in CF group.     

Macrotermes mounds as sites for tree regeneration in a Sudanian woodland (Burkina Faso)

The importance of mounds created by Macrotermes subhyalinus as safe site for tree regeneration was analysed in a savannah woodland of Burkina Faso. Plantlets (height <1.5 m) were sampled and followed over an year in 72 × 4 m² quadrats located on M. subhyalinus mounds and adjacent areas. The mechanisms of regeneration and plantlet mortality were also determined. We identified three regeneration mechanisms: seedlings regenerated by seed (abundant on mounds), sprouts (abundant on adjacent areas) and root suckers (a rare case on both sites). A total of 37 species representing 17 families and 30 genera were found on all quadrats, of which 29 species were found on termite mounds and 22 species on adjacent areas. Species richness and density of plantlets at the 4 m² scale were higher on mounds than in the adjacent area (P < 0.05). Among plantlet categories, seedling density was significantly different among microhabitats (P < 0.001) and across sampling periods (P < 0.01) and, the majority of plantlet individuals appeared within the 0–25 cm height class. The mortality of plantlets and particularly seedling mortality differed significantly between microhabitats (P < 0.01) and between periods (P < 0.01), whereas more than half the variation in the death of Acacia erythrocalyx seedlings (the most abundant species) were related to the density of the live seedlings of the same species (P < 0.001). The observed mortality rate was way below 50%; plantlet density remained higher on mound during sampling periods as compared to the adjacent area. It can thus be concluded that Macrotermes termite mounds are favourable sites for the recruitments of woody plants in savannah woodlands.     

Saquinavir enhances the mucosal toxicity of infusional cyclophosphamide, doxorubicin, and etoposide in patients with HIV-associated non-Hodgkin''s lymphoma

Protease inhibitors are an important new class of agents for the treatment of human immunodeficiency virus (HIV) infection. The purpose of our trial was to determine the feasibility of combining the protease inhibitor saquinavir with a 96-hour continuous intravenous infusion of cyclophosphamide (800 mg/M²), doxorubicin (50mg/M², and etoposide (240 mg/M²) (CDE) plus filgrastim in patients with non-Hodgkin's lymphoma associated with HIV infection. The effect of saquinavir on CDE-induced myelosuppression, CD4 lymphopenia, and non-hematologic toxicity was also sought. Twelve patients with HIV-related lymphoma received CDE every 28 or more days. All patients received saquinavir (600 mg PO TID), filgrastim andPneumocystis carinii and fungal prophylaxis. Patients also received either stavudine (n=2) or boths stavudine and didanosine (n=10). Toxicity was analyzed using the NCI Common Toxicity Criteria for each cycle and the data were compared with the data from our prior study of CDE plus didanosine. An interim analysis was performed after accrual of the first 12 patients in order to assess toxicity. Severe (grade 3 or 4) mucositis occurred in eight of 12 patients (67%) treated with CDE plus saquinavir compared with three of 25 patients (12%) in our prior study treated with CDE without saquinavir (P<0.001). In logistic regression analysis, saquinavir use was the only factor associated with a significantly greater risk of severe mucositis (relative risk 7.9;P=0.03). Saquinavir use was not associated with a significant difference in the incidence of febrile neutropenia, prolonged neutropenia, chemotherapy dose reduction, or in the degree of myelosuppression. The decrease in CD4 lymphocytes for patients treated with saquinavir (absolute decrease of 23/μL, or a 26% decrease from baseline) was significantly less than for patients treated without saquinavir in the prior study (absolute decrease of 91/μL, or 42% decrease from baseline;P=0.05). Four of 10 patients (40%) treated with saquinavir had an increase in CD4 lymphocytes of ≥10/μL compared with none of 25 patients (0%) treated without saquinavir (P<0.001). Combination of the protease inhibitor saquinavir with infusional CDE in patients with HIV-associated lymphoma was associated with a significant increase in the incidence of severe mucositis. This finding suggests that saquinavir may alter the metabolism of one of more of the cytotoxic agents in the CDE regimen, and underscores the need for careful investigation regarding the use of the protease inhibitors in patients receiving chemotherapy.     

Above- and Belowground Net Primary Production in a Temperate Mixed Deciduous Forest

Our current ability to detect and predict changes in forest ecosystem productivity is constrained by several limitations. These include a poor understanding of belowground productivity, the short duration of most analyses, and a need for greater examination of species- or community-specific variability in productivity studies. We quantified aboveground net primary productivity (ANPP) over 3 years (1999–2001), and both belowground NPP (BNPP) and total NPP over 2 years (2000–2001) in both mesic and xeric site community types of the mixed mesophytic forest of southeastern Kentucky to examine landscape variability in productivity and its relation with soil resource [water and nitrogen (N)] availability. Across sites, ANPP was significantly correlated with N availability (R² = 0.58, P = 0.028) while BNPP was best predicted by soil moisture content (R² = 0.72, P = 0.008). Because of these offsetting patterns, total NPP was unrelated to either soil resource. Interannual variability in growing season precipitation during the study resulted in a 50% decline in mesic site litter production, possibly due to a lag effect following a moderate drought year in 1999. As a result, ANPP in mesic sites declined 27% in 2000 compared to 1999, while xeric sites had no aboveground production differences related to precipitation variability. If global climate change produces more frequent occurrences of drought, then the response of mesic sites to prolonged moisture deficiency and the consequences of shifting carbon (C) allocation on C storage will become important questions.     

Temporal Evolution of Parotid Volume and Parotid Apparent Diffusion Coefficient in Nasopharyngeal Carcinoma Patients Treated by Intensity-Modulated Radiotherapy Investigated by Magnetic Resonance Imaging: A Pilot Study

Purpose

To concurrently quantify the radiation-induced changes and temporal evolutions of parotid volume and parotid apparent diffusion coefficient (ADC) in nasopharyngeal carcinoma (NPC) patients treated by intensity-modulated radiotherapy by using magnetic resonance imaging (MRI).

Materials and Methods

A total of 11 NPC patients (9 men and 2 women; 48.7 ± 11.7 years, 22 parotid glands) were enrolled. Radiation dose, parotid sparing volume, severity of xerostomia, and radiation-to-MR interval (RMI) was recorded. MRI studies were acquired four times, including one before and three after radiotherapy. The parotid volume and the parotid ADC were measured. Statistical analysis was performed using SPSS and MedCalc. Bonferroni correction was applied for multiple comparisons. A P value less than 0.05 was considered as statistically significant.

Results

The parotid volume was 26.2 ± 8.0 cm³ before radiotherapy. The parotid ADC was 0.8 ± 0.15 × 10⁻³ mm²/sec before radiotherapy. The parotid glands received a radiation dose of 28.7 ± 4.1 Gy and a PSV of 44.1 ± 12.6%. The parotid volume was significantly smaller at MR stage 1 and stage 2 as compared to pre-RT stage (P < .005). The volume reduction ratio was 31.2 ± 13.0%, 26.1 ± 13.5%, and 17.1 ± 16.6% at stage 1, 2, and 3, respectively. The parotid ADC was significantly higher at all post-RT stages as compared to pre-RT stage reciprocally (P < .005 at stage 1 and 2, P < .05 at stage 3). The ADC increase ratio was 35.7 ± 17.4%, 27.0 ± 12.8%, and 20.2 ± 16.6% at stage 1, 2, and 3, respectively. The parotid ADC was negatively correlated to the parotid volume (R = -0.509; P < .001). The parotid ADC was positively associated with the radiation dose significantly (R² = 0.212; P = .0001) and was negatively associated with RMI significantly (R² = 0.203; P = .00096) significantly. Multiple regression analysis further showed that the post-RT parotid ADC was related to the radiation dose and RMI significantly (R² = 0.3580; P < .0001). At MR stage 3, the parotid volume was negatively associated with the dry mouth grade significantly (R² = 0.473; P < .0001), while the parotid ADC was positively associated with the dry mouth grade significantly (R² = 0.288; P = .015).

Conclusion

Our pilot study successfully demonstrates the concurrent changes and temporal evolution of parotid volume and parotid ADC quantitatively in NPC patients treated by IMRT. Our results suggest that the reduction of parotid volume and increase of parotid ADC are dominated by the effect of acinar loss rather than edema at early to intermediate phases and the following recovery of parotid volume and ADC toward the baseline values might reflect the acinar regeneration of parotid glands.     

Linking White-Tailed Deer Density,Nutrition, and Vegetation in a Stochastic Environment

Density-dependent behavior underpins white-tailed deer (Odocoileus virginianus) theory and management application in North America, but strength or frequency of the phenomenon has varied across the geographic range of the species. The modifying effect of stochastic environments and poor-quality habitats on density-dependent behavior has been recognized for ungulate populations around the world, including white-tailed deer populations in South Texas, USA. Despite the importance of understanding mechanisms influencing density dependence, researchers have concentrated on demographic and morphological implications of deer density. Researchers have not focused on linking vegetation dynamics, nutrition, and deer dynamics. We conducted a series of designed experiments during 2004–2012 to determine how strongly white-tailed deer density, vegetation composition, and deer nutrition (natural and supplemented) are linked in a semi-arid environment where the coefficient of variation of annual precipitation exceeds 30%. We replicated our study on 2 sites with thornshrub vegetation in Dimmit County, Texas. During late 2003, we constructed 6 81-ha enclosures surrounded by 2.4-m-tall woven wire fence on each study site. The experimental design included 2 nutrition treatments and 3 deer densities in a factorial array, with study sites as blocks. Abundance targets for low, medium, and high deer densities in enclosures were 10 deer (equivalent to 13 deer/km²), 25 deer (31 deer/km²), and 40 deer (50 deer/km²), respectively. Each study site had 2 enclosures with each deer density. We provided deer in 1 enclosure at each density with a high-quality pelleted supplement ad libitum, which we termed enhanced nutrition; deer in the other enclosure at each density had access to natural nutrition from the vegetation. We conducted camera surveys of deer in each enclosure twice per year and added or removed deer as needed to approximate the target densities. We maintained >50% of deer ear-tagged for individual recognition. We maintained adult sex ratios of 1:1–1:1.5 (males:females) and a mix of young and older deer in enclosures. We used reconstruction, validated by comparison to known number of adult males, to make annual estimates of density for each enclosure in analysis of treatment effects. We explored the effect of deer density on diet composition, diet quality, and intake rate of tractable female deer released into low- and high-density enclosures with natural nutrition on both study sites (4 total enclosures) between June 2009 and May 2011, 5 years after we established density treatments in enclosures. We used the bite count technique and followed 2–3 tractable deer/enclosure during foraging bouts across 4 seasons. Proportion of shrubs, forbs, mast, cacti, and subshrubs in deer diets did not differ (P > 0.57) between deer density treatments. Percent grass in deer diets was higher (P = 0.05) at high deer density but composed only 1.3 ± 0.3% (SE) of the diet. Digestible protein and metabolizable energy of diets were similar (P > 0.45) between deer density treatments. Likewise, bite rate, bite size, and dry matter intake did not vary (P > 0.45) with deer density. Unlike deer density, drought had dramatic (P ≤ 0.10) effects on foraging of tractable deer. During drought conditions, the proportion of shrubs and flowers increased in deer diets, whereas forbs declined. Digestible protein was 31%, 53%, and 54% greater (P = 0.06) during non-drought than drought during autumn, winter, and spring, respectively. We studied the effects of enhanced nutrition on the composition and quality of tractable female deer diets between April 2007 and February 2009, 3 years after we established density treatments in enclosures. We also estimated the proportion of supplemental feed in deer diets. We used the 2 low-density enclosures on each study site, 1 with enhanced nutrition and 1 with natural nutrition (4 total enclosures). We again used the bite count technique and 2–3 tractable deer living in each enclosure. We estimated proportion of pelleted feed in diets of tractable deer and non-tractable deer using ratios of stable isotopes of carbon. Averaged across seasons and nutrition treatments, shrubs composed a majority of the vegetation portion of deer diets (44%), followed by mast (26%) and forbs (15%). Enhanced nutrition influenced the proportion of mast, cacti, and flowers in the diet, but the nature and magnitude of the effect varied by season and year. The trend was for deer in natural-nutrition enclosures to eat more mast. We did not detect a statistical difference (P = 0.15) in the proportion of shrubs in diets between natural and enhanced nutrition, but deer with enhanced nutrition consumed 7–24% more shrubs in 5 of 8 seasons. Deer in enhanced-nutrition enclosures had greater (P = 0.03) digestible protein in their overall diet than deer in natural-nutrition enclosures. The effect of enhanced nutrition on metabolizable energy in overall diets varied by season and was greater (P < 0.04) for enhanced-nutrition deer during summer and autumn 2007 and winter 2008. In the enhanced-nutrition treatment, supplemental feed averaged 47–80% of the diet of tractable deer. Of non-tractable deer in all density treatments with enhanced nutrition, 97% (n = 128 deer) ate supplemental feed. For non-tractable deer averaged across density treatments, study sites, and years, percent supplemental feed in deer diets exceeded 70% for all sex and age groups. We determined if increasing deer density and enhanced nutrition resulted in a decline in preferred forbs and shrubs and an increase in plants less preferred by deer. We sampled all 12 enclosures via 20, 50-m permanent transects in each enclosure. Percent canopy cover of preferred forbs was similar (P = 0.13) among deer densities averaged across nutrition treatments and sampling years (low density: = 8%, SE range 6–10; medium density: 5%, 4–6; high density: 4%, 3–5; SE ranges are presented because SEs associated with backtransformed means are asymetrical). Averaged across deer densities, preferred forb canopy cover was similar between nutrition treatments in 2004; but by 2012 averaged 20 ± 17–23% in enhanced-nutrition enclosures compared to 10 ± 8–13% in natural-nutrition enclosures (P = 0.107). Percent canopy cover of other forbs, preferred shrubs, other shrubs, and grasses, as well as Shannon's index, evenness, and species richness were similar (P > 0.10) among deer densities, averaged across nutrition treatments and sampling years. We analyzed fawn:adult female ratios, growth rates of fawns and yearlings, and survival from 6 to 14 months of age and for adults >14 months of age. We assessed adult body mass and population growth rates (lambda apparent, λ_APP) to determine density and nutrition effects on deer populations in the research enclosures during 2004–2012. Fawn:adult female ratios declined (P = 0.04) from low-medium density to high density in natural-nutrition enclosures but were not affected (P = 0.48) by density in enhanced nutrition enclosures although, compared to natural nutrition, enhanced nutrition increased fawn:adult female ratios by 0.15 ± 0.12 fawns:adult female at low-medium density and 0.44 ± 0.17 fawns:adult female at high density. Growth rate of fawns was not affected by deer density under natural or enhanced nutrition (P > 0.17) but increased 0.03 ± 0.01 kg/day in enhanced-nutrition enclosures compared to natural nutrition (P < 0.01). Growth rate of yearlings was unaffected (P > 0.71) by deer density, but growth rate increased for males in some years at some density levels in enhanced-nutrition enclosures. Adult body mass declined in response to increasing deer density in natural-nutrition enclosures for both adult males (P < 0.01) and females (P = 0.10). Enhanced nutrition increased male body mass, but female mass did not increase compared to natural nutrition. Survival of adult males was unaffected by deer density in natural- (P = 0.59) or enhanced- (P = 0.94) nutrition enclosures. Survival of adult females was greatest in medium-density enclosures with natural nutrition but similar at low and high density (P = 0.04). Enhanced nutrition increased survival of females (P < 0.01) and marginally for males (P = 0.11). Survival of fawns 6–14 months old was unaffected (P > 0.35) by density in either natural- or enhanced-nutrition treatments but was greater (P = 0.04) under enhanced nutrition. Population growth rate declined (P = 0.06) with increasing density in natural-nutrition enclosures but not (P = 0.55) in enhanced nutrition. Enhanced nutrition increased λ_APP by 0.32. Under natural nutrition, we found only minor effects of deer density treatments on deer diet composition, nutritional intake, and plant communities. However, we found density-dependent effects on fawn:adult female ratios, adult body mass, and population growth rate. In a follow-up study, deer home ranges in our research enclosures declined with increasing deer density. We hypothesized that habitat quality varied among home ranges and contributed to density-dependent responses. Variable precipitation had a greater influence on deer diets, vegetation composition, and population parameters than did deer density. Also, resistance to herbivory and low forage quality of the thornshrub vegetation of our study sites likely constrained density-dependent behavior by deer. We posit that it is unlikely that, at our high-density (50 deer/km²) and perhaps even medium-density (31 deer/km²) levels, negative density dependence would occur without several wet years in close association. In the past century, this phenomenon has only happened once (1970s). Thus, density dependence would likely be difficult to detect in most years under natural nutrition in this region. Foraging by deer with enhanced nutrition did not result in a reduction in preferred plants in the vegetation community and had a protective effect on preferred forbs because ≤53% of deer diets consisted of vegetation. However, enhanced nutrition improved fitness of individual deer and deer populations, clearly demonstrating that nutrition is limiting for deer populations under natural conditions in western South Texas. © 2019 The Authors. Wildlife Monographs published by Wiley Periodicals, Inc. on behalf of The Wildlife Society.     

Effects of spatial disturbance on common loon nest site selection and territory success

The common loon (Gavia immer) breeds during the summer on northern lakes and water bodies that are also often desirable areas for aquatic recreation and human habitation. In northern New England, we assessed how the spatial nature of disturbance affects common loon nest site selection and territory success. We found through classification and regression analysis that distance to and density of disturbance factors can be used to classify observed nest site locations versus random points, suggesting that these factors affect loon nest site selection (model 1: Correct classification = 75%, null = 50%, K = 0.507, P < 0.001; model 2: Correct classification = 78%, null = 50%, K = 0.551, P < 0.001). However, in an exploratory analysis, we were unable to show a relation between spatial disturbance variables and breeding success (P = 0.595, R² = 0.436), possibly because breeding success was so low during the breeding seasons of 2007–2008. We suggest that by selecting nest site locations that avoid disturbance factors, loons thereby limit the effect that disturbance will have on their breeding success. Still, disturbance may force loons to use sub-optimal nesting habitat, limiting the available number of territories, and overall productivity. We advise that management efforts focus on limiting disturbance factors to allow breeding pairs access to the best nesting territories, relieving disturbance pressures that may force sub-optimal nest placement. © 2011 The Wildlife Society     

立体定向放疗联合内分泌治疗对转移性激素敏感性前列腺癌患者免疫功能和生活质量的影响

摘要 目的：探讨立体定向放疗（SBRT）联合内分泌治疗对转移性激素敏感性前列腺癌患者生活质量、免疫功能的影响。方法：选取我院2015年2月~2017年2月期间收治的转移性激素敏感性前列腺癌患者100例,根据信封抽签法将患者分为对照组（50例）和放疗组（50例）,对照组给予内分泌治疗,放疗组在对照组的基础上联合SBRT治疗。对比两组前列腺特异性抗原（PSA）进展时间、PSA缓解率、治疗期间不良反应状况、3年生存率、免疫功能（CD3⁺、CD4⁺、CD8⁺、CD4⁺/CD8⁺）和扩展性前列腺癌复合指数量表（EPIC）各项评分。结果：随访3年,对照组有2例失访、放疗组有3例失访,放疗组的PSA进展时间长于对照组（P<0.05）,放疗组的3年生存率高于对照组（P<0.05）。治疗后,两组CD3⁺、CD4⁺/CD8⁺、CD4⁺均下降,但放疗组较对照组升高（P<0.05）,两组治疗后CD8⁺均升高,但放疗组较对照组降低（P<0.05）。治疗后6个月,放疗组性功能、激素功能、泌尿功能、肠道功能领域评分均高于对照组（P<0.05）。两组不良反应总发生率、PSA缓解率组间对比无差异（P>0.05）。结论：SBRT联合内分泌治疗转移性激素敏感性前列腺癌患者,可延长患者PSA进展时间,减轻免疫抑制,提高患者生活质量,同时还可改善患者的预后,患者耐受性良好。     

Rôle de la TEP au 18F-FDG dans l’évaluation des volumes cibles chez des patients atteints de CBNPC traités par radiochimiothérapie

Currently ¹⁸F-FDG-PET is the gold standard to evaluate tumor response after chemotherapy in patients with advanced or metastatic non-small cell lung cancer (NSCLC). PET can also determine the volumes to be treated by radiotherapy, in inoperable patients. The aim of our mixed (prospective and retrospective) study concerned 28 patients with NSCLC, was to quantify the variation of the metabolic activity of lesions and their volumes after chemotherapy. We also studied the impact of change of these volumes on the definition of radiotherapy target volumes. Patients with stage II–IV and inoperable NSCLC were included. Two PET scans were performed: before treatment (PET1), then after two to six courses of chemotherapy (PET2). Of the 28 patients included, we observed complete metabolic response in six patients (21%), partial metabolic response in 13 patients (46%), stable disease in seven patients (25%), and progressive metabolic disease in two patients (7%), according to the PERCIST criteria. We observed significant variation (P < 0.001) of metabolic activity (estimated by SULpeak or SUVmax) for primary tumor as well as for overall lesions between the two PET scans. Thus, the target volumes of radiotherapy decreased significantly (P < 0.01) in PET2. Our results confirm that ¹⁸F-FDG-PET is not only a powerful technique for treatment evaluation but also a useful tool for radiotherapy planning after chemotherapy, in the context of personalized treatments.     

Characterization of T-lymphocyte subpopulations infiltrating primary breast cancer

Summary Characterization of T-lymphocyte subpopulations adjacent to and infiltrating the primary tumor of breast cancer was carried out using a direct immunofluorescence procedure with the antibodies anti-(Leu-2a) for suppressor/cytotoxic (CD8⁺) and anti-(Leu-3a) for helper/inducer (CD4⁺) T-lymphocytes. Fifty-six primary malignant tumors with lymphoid infiltration were studied. The majority (58.9%) were infiltrating duct carcinoma. There were metastases to axillary lymph nodes in 6.67% of the patients. Massive lymphoid infiltration (>40 lymphocytes per ×400 microscopic field) was found in 19.6% of the tumors and moderate infiltration (20–40 lymphocytes per field) in 51.8%. In all the tumors studied there was a reversed CD4⁺/CD8⁺ ratio as compared to that found in normal peripheral blood. In 66.1% the CD4⁺/CD8⁺ ratio (helper/suppressor) was less than 1.0. The reversed ratio was due to a significant decrease in the number of helper cells (P<0.0005). The most significant drop was in the stroma area (P<0.0001) as well as in the tumor tissue (P=0.001). Of particular interest was the significant positive correlation between the age of the patients and an increased number of CD4⁺lymphocytes in the stroma (P=0.02). Significant negative correlations were found between a reduced number of CD4⁺ lymphocytes or CD4⁺/CD8⁺ ratio and several histological parameters: tumor diameter, pleomorphism, nucleus/cytoplasm ratio. There was also a significant positive correlation between the total number of CD8⁺ lymphocytes infiltrating the tumor tissue and the number of axillary lymph nodes with metastatic disease (P=0.03). It is suggested that the reversed ratio of CD4⁺/CD8⁺ lymphocytes may significantly affect the host/tumor immune surveillance.     

Assessment of immunologic response and recurrence patterns among patients with clinical recurrence after vaccination with a preventive HER2/neu peptide vaccine: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02

Background  E75, a HER2/neu immunogenic peptide, is expressed in breast cancer (BCa). We have performed clinical trials of E75 + GM-CSF vaccine in disease-free, node-positive and node-negative BCa patients at high recurrence risk and recurrences were noted in both control and vaccine groups. Methods  Among the 186 BCa patients enrolled, 177 completed the study. Patients were HLA typed; the HLA-A2⁺/A3⁺ patients were vaccinated; HLA-A2⁻/A3⁻ patients were followed as controls. Standard clinicopathological factors, immunologic response to the vaccine, and recurrences were collected and assessed. Results  The control group recurrence rate was 14.8 and 8.3% in the vaccinated group (P = 0.17). Comparing the 8 vaccinated recurrences (V-R) to the 88 vaccinated nonrecurrent patients (V-NR), the V-R group had higher nodal stage (≥N2: 75 vs. 5%, P = 0.0001) and higher grade tumors (%grade 3: 88 vs. 31%, P = 0.003). The V-R group did not fail to respond immunologically as noted by equivalent dimer responses and post-DTH responses. Compared to control recurrent patients (C-R), V-R patients trended toward higher-grade tumors and hormone-receptor negativity. C-R patients had 50% bone-only recurrences, compared to V-R patients with no bone-only recurrences (P = 0.05). Lastly, V-R mortality rate was 12.5% compared with 41.7% for the C-R group (P = 0.3). Conclusions  The vaccinated patients who recurred had more aggressive disease compared to V-NR patients. V-R patients had no difference in immune response to the vaccine either in vitro or in vivo. V-R patients, when compared to C-R patients, trended towards more aggressive disease, decreased recurrence rates, decreased mortality, and no bone-only recurrences. Supported by the United States Military Cancer Institute and the Department of Clinical Investigation at Walter Reed Army Medical Center. Funded primarily by the Clinical Breast Care Project. The opinions or assertions contained herein are the private views of the authors and are not to be construed as official or reflecting the views of the Department of the Army, the Department of the Navy, or the Department of Defense. This work represents original research that has not been submitted elsewhere for publication.     

Primary antiphospholipid antibody syndrome—one further aspect of thrombophilia in overweight and obese patients with venous thromboembolism

Objective: Overweight and obesity are established risk factors for venous thromboembolism (VTE). We examined the difference in the frequency of primary antiphospholipid antibody syndrome (PAPS) in VTE patients according to their BMI. Design and Methods: We included 998 VTE patients treated at our institution between 2009 and 2011 in a retrospective data analysis. Thrombophilia screening including evaluation for APS (lupus anticoagulant, anti‐cardiolipin, and anti‐B2‐glycoprotein‐I IgG and IgM antibodies) was performed in all patients. Results: PAPS was diagnosed in 6.8% (24/355) of normal weight (BMI < 24 kg/m²) VTE patients, in 11.1% (50/452) of overweight (BMI 25–30 kg/m²) VTE patients, and in 15.7% (30/191) of obese (BMI > 31 kg/m²) VTE patients. The difference of PAPS occurrence between these groups was statistically significant (P = 0.001). PAPS patients demonstrated higher fibrinogen levels as compared to non‐PAPS patients (median 416.0 md/dl vs. 352.0 mg/dl, P = 0.001). Furthermore, fibrinogen levels increased significantly according to the body weight of patients (median normal weight patients 330.0 mg/dl vs. overweight patients 359.0 mg/dl vs. obese patients 415.0 mg/dl, P = 0.001). Conclusion: PAPS seems to be more frequent in overweight and obese patients. As PAPS patients showed significantly higher fibrinogen levels and as fibrinogen levels increased significantly according to the body weight of patients, an elevated inflammatory state in overweight and obese patients as a reason for the increased PAPS occurrence can be assumed.     

Insulin requirement profiles and related factors of insulin pump therapy in patients with type 2 diabetes

Continuous subcutaneous insulin infusion(CSII) is an effective therapy to control hyperglycemia in both patients with type 1 diabetes and type 2 diabetes.However,there is little data investigating the insulin dose setting during CSII therapy in type 2 diabetes to achieve optimal glycemic control and avoid the risk of hypoglycemia.Thus,this study is aimed to assess the dose characteristics of insulin requirement and explore the related clinical factors in patients with type 2 diabetes who were treated with CSII.A total of 327 patients(195 males) aged 52.9±12.5 years old were included in this study.Patients were treated with CSII to achieve the target fasting capillary blood glucose(4.4-7.0 mmol L ~(-1)) and 2-h postprandial capillary blood glucose(4.4-10.0 mmol L ~(-1)) by adjusting insulin infusion according to the seven-point capillary blood glucose profiles.Total daily insulin dose(TDD),total daily insulin dose per kilogram(TDD kg-1) and the ratio of total basal insulin dose(TBD) to TDD(%TBa) were calculated after patients achieved the glucose targets for at least 3 days via 1-2 weeks of CSII treatment.And insulin dose,insulin dosing patterns and the relevant clinical factors were analyzed.The mean ratio of basal/bolus insulin distribution of all patients was 40%:60%.Patients with central obesity needed more TDD(51.3±17.1 U versus 43.5±14.0 U,P0.05) and TDD kg ~(-1)(0.8±0.3 U kg ~(-1) versus 0.7±0.2 U kg ~(-1),P0.05) than those without central obesity.Pearson's correlation analysis demonstrated that TDD was positively correlated with body mass index(BMI),waist circumference(WC),baseline fasting plasma glucose(FPG),fasting C-peptide level,2 h-postprandial C-peptide level and time to achieve glycemic target(all P0.05);TDD kg ~(-1) was positively correlated with waist-to-hip ratio(WHR),baseline FPG,glycosylated hemoglobin Ale(HbAlc),fasting C-peptide level and time to achieve glycemic target,and negatively correlated with BMI(all P0.05).Multiple linear regression analyses revealed that BMI(β=1.796,P0.01),WC(β=0.109,P0.01),baseline FPG(β=1.459,P0.01) and HbAlc(β=0.930,P=0.021) were independently related to TDD.Gender(β=-0.107,P=0.003),WC(β=0.005,P=0.029),baseline FPG(β=0.025,P0.01) and HbAlc(β=0.016,β=0.007) were independently associated with TDD kg ~(-1).Gender(β=-0.015,P=0.048) and disease duration(β=0.134,P=0.029) were independently associated with %TBa.%TBa is around 40% in Chinese patients with type 2 diabetes treated with CSII when glycemic control is achieved.In addition to body weight or BMI,WC and glucose levels before CSII should be considered to set TDD.Patients with central obesity or poor glycemic control might need more TDD.Higher %TBa should be considered in female patients or patients with longer disease duration.     

The Chronic Effects of Whey Proteins on Blood Pressure,Vascular Function,and Inflammatory Markers in Overweight Individuals

Limited evidence suggests that dairy whey protein may be the major dairy component that is responsible for health benefits currently associated with increased dairy consumption. Whey proteins may reduce blood pressure and improve cardiovascular health. This study evaluated the effects of whey protein supplementation on blood pressure, vascular function and inflammatory markers compared to casein and glucose (control) supplementation in overweight/obese individuals. The subjects were randomized to either whey protein, casein or glucose supplementation for 12 weeks according to a parallel design. In all, 70 men and women with a mean (±s.e.m.) BMI (kg/m²) of 31.3 ± 0.8 completed the study. Systolic blood pressure (SBP) decreased significantly at week 6 compared to baseline in the whey and casein groups, (P = 0.028 and P = 0.020, respectively) and at week 12 (P = 0.020, and P = 0.017, respectively). Diastolic blood pressure (DBP) decreased significantly compared to baseline in the whey and casein groups (P = 0.038 and P = 0.042, respectively) at week 12. DBP decreased significantly in the whey and casein groups (P = 0.025, P = 0.038, respectively) at week 12 compared to the control group. Augmentation index (AI) was significantly lower from baseline at 12 weeks (P = 0.021) in the whey group. AI decreased significantly in the whey group at 12 weeks compared to control (P = 0.006) and casein (P = 0.006). There were no significant changes in inflammatory markers within or between groups. This study demonstrated that supplementation with whey protein improves blood pressure and vascular function in overweight and obese individuals.     

The physical phenotype of girls and women with Turner syndrome is not X-imprinted

Certain behavioral and metabolic aspects of Turner syndrome (TS) are attributed to X-chromosome genomic imprinting. To investigate the possible contribution of imprinting to the physical features of the TS phenotype in live-born individuals, we genotyped the single normal X-chromosome in subjects with TS who all underwent a comprehensive evaluation as part of the NIH genotype–phenotype protocol. All had physical examinations, auxological measurements and imaging of the renal and cardiovascular systems. Absolute height and height as a percent of predicted height was the same in X^M (n = 56) and X^P (n = 23) subjects that had reached final height and were not growth hormone treated. Interestingly, adult height was significantly correlated with maternal but not paternal heights in both X^M and X^P groups. Neck webbing was found in 35% of the X^M (n = 133) and 22% of the X^P (n = 50) groups (P = 0.11). Renal anomalies were present in 24% of X^M and 25% of X^P groups (P = 0.9). Bicuspid aortic valve was found in 26% of X^M and 24% of X^P groups (P = 0.83), and any cardiovascular anomaly (abnormal aortic valve, aortic coarctation, elongated transverse aortic arch, anomalous pulmonary venous connection, left superior vena cava) affected 55% of X^M and 52% of X^P groups. Thus, we found no evidence for X-linked genomic imprinting effects on stature or lymphatic, renal or cardiovascular development in TS. Our sample size was sufficient to exclude such effects within 95% confidence limits. We did demonstrate a selective maternal effect on final stature that was independent of X-chromosome origin, suggesting potential autosomal imprinting effects on growth revealed by X monosomy.     

Evaluation of Electric Fencing to Inhibit Feral Pig Movements

Abstract: Natural resource managers and agricultural producers are seeking innovative tools to minimize damages caused by rapidly expanding feral pig (Sus scrofa) populations. One tool that has received little scientific inquiry is the use of exclusion fences to protect economically and ecologically sensitive areas. Our objectives were to evaluate the ability of electric fencing to minimize feral pig movements in a captive setting as well as in rangeland and agriculture land. In captivity, we tested a 1-, 2-, and 3-strand electric fence. In our captive trial, we found 65% fewer intrusions (F_2,18 = 20.46, P < 0.001) for electric fences (x̄ = 12.4, SE = 2.8) compared with nonelectric fences (x̄ = 35.6, SE = 6.9). We found no difference (F_2,9 = 1.85, P = 0.212) for 1-strand (x̄ = 28.1, SE = 7.8), 2-strand (x̄ = 14.2, SE = 3.2), and 3-strand (x̄ = 16.9, SE = 4.3) electric fences. However, we found 50% and 40% fewer crossings for the 2- and 3-strand fences, respectively, compared with the 1-strand fence. In our rangeland trial, we found 49% fewer intrusions (F_2,18 =4.39, P = 0.028) into bait stations with a 2-strand electric fence (x̄ =4.1, SE = 1.8) compared with no fence (x̄ =8.1, SE = 2.4). Finally, in our agriculture trial, we found 64% less damage (X²₂ = 5.77, P = 0.016) to sorghum crops with a 2-strand electric fence (x̄ = 4.48, SE = 0.01%) compared with no electric fence (x̄ = 12.46, SE = 0.03%). Furthermore we found no (X¹₁ = 3.72, P = 0.054) wildlife pathways in areas with an electric fence (x̄ = 0.0, SE =0.0) compared with no fence (x̄ = 2.4, SE= 1.3). No electric fence design we tested was 100% pig-proof However, we found electric fencing restricted feral pig movements. Combining electric fencing with other damage control methods in an integrated management program may be the best method for alleviating feral pig damages.