Sequential Adjuvant CMF Chemotherapy Followed by Radiotherapy in the Treatment of Early-Stage Breast Cancer: The Lankenau Hospital Experience

Abstract: The optimal timing of systemic cyclophosphamide, methotrexate, 5-fluorouracil (CMF) chemotherapy and local radiation in adjuvant breast cancer has been a debatable subject. To evaluate the Lankenau Hospital experience with sequential CMF chemotherapy followed by radiation in the adjuvant therapy of stage I and stage II breast cancer we reviewed the records of patients at our center. This group of 34 patients was treated in a homogenous manner, all receiving standard CMF for six cycles followed by radiotherapy after lumpectomy with axillary lymph node dissection. The radiation course was 5040cGy to the entire breast (28 fractions in 45 elapsed days) followed by a boost to the tumor site of 1800cGy in 10 fractions. Thirty-four patients were identified and followed for an average of 5 years (range 1.5–11.5 years). One patient had local recurrence and with subsequent treatment is disease-free at 5 years postrecurrence (8 years from initial diagnosis). Two deaths were not breast-cancer related (1 myocardial infarction at year 3, 1 melanoma at year 7.5). The estimated probability of no relapse at 5 years and 8 years by Kaplan-Meier analysis is 79% and 60% respectively. Overall and disease-free survival in this group of patients treated with breast-conserving surgery and CMF chemotherapy followed by radiation is excellent. There appears to be no detriment to delaying radiotherapy until full doses of systemic treatment are given as local recurrence was rare (6%) and was amenable to further treatment.     

Selective Effect of Adjuvant Arthritis on the Disposition of Propranolol Enantiomers in Rats Detected Using a Stereospecific HPLC Assay

Nonstereospecific studies have indicated that the pharmacokinetics of propranolol (PR) are altered in inflammatory conditions such as arthritis. However, as the kinetics and dynamics of PR are stereoselective, we examined the effect of adjuvant arthritis (AA) on the disposition of the individual enantiomers. A novel normal-phase stereospecific HPLC assay for PR was developed involving chiral derivatization with S-(naphthyl)ethyl isocyanate and fluorescence detection. Oral and iv doses of racemic PR were administered to control and AA rats (n = 6). AA had no significant effect on either clearance or S:R ratio after iv doses. On the other hand, after oral doses, clearance was significantly decreased in AA. Although significant for both enantiomers, this effect was more pronounced on the less active R-enantiomer. The AUC R:S ratio was, therefore, significantly altered (AA, 14 ± 3.0; control, 4.3 ± 1.2). Increased total (S + R) plasma concentrations of PR in AA, possibly due to a reduced intrinsic clearance, therefore, reflect mainly increased concentrations of the less active R-enantiomer.     

尼美舒利对佐剂性关节炎大鼠的治疗作用研究

尼美舒利(Nime)0．6、30、15mg·kg^-1对佐剂性关节炎大鼠的原发性和继发性炎症反应均有明显的抑制作用，用药组继发性炎痘反应的全身症状也明显减轻，而Nime对佐剂性关节炎大鼠低下的脾细胞增殖反应和腹腔巨噬细胞产生过高的IL-1活性却无明显影响，提示Nime无明显的免疫作用，该结果表明，Nime对佐剂性关节炎大鼠有明显的治疗作用，这一作用可能与Nime有较强的抗炎作甩有关。     

The effect of adjuvant therapy with or without tamoxifen on the endocrine function of patients with breast cancer

The ovarian and pituitary functions of 64 operable breast cancer patients undergoing adjuvant therapy with cytotoxic chemotherapy and/or tamoxifen were investigated. The post menopausal patients, divided into 3 treatment groups, one with tamoxifen alone, one with tamoxifen and chemotherapy and the other with chemotherapy alone had serum estradiol 17-β (E2) and progesterone levels lower than the evaluable limits. Although there was no significant difference in the level of estrone sulfate (E1-S) between these three groups, the level of lutainizing hormone (LH) and follicle stimulating hormone (FSH) in the patients treated with tamoxifen alone and tamoxifen and chemotherapy were significantly lower than those treated with chemotherapy alone. The decrease in gonadotropin levels induced by tamoxifen treatment was reversible as it appeared after the initiation of tamoxifen and recovered after its cessation. In the premenopausal patients, a group treated with tamoxifen and chemotherapy had significantly higher E1-S, E2 and progesterone levels and significantly lower gonadotropin levels than a group treated with chemotherapy alone or one treated with a cyclophosphamide regimen. These increases in the levels of estrogen and progesterone were also reversible, and induced by tamoxifen. Thus, adjuvant endocrinochemotherapy causes profound alteration in the hypothalamo-pituitary-ovarian axis and therefore, monitoring a variety of hormonal levels is thought to be necessary for assessing the consequences of adjuvant therapy in breast cancer patients, especially in premenopausal patients using tamoxifen.     

Immunoadjuvant action of liposomes for entrapped Japanese Encephalitis virus E－glucoprotein

ＩｍｍｕｎｏａｄｊｕｖａｎｔａｃｔｉｏｎｏｆｌｉｐｏｓｏｍｅｓｆｏｒｅｎｔｒａｐｐｅｄＪａｐａｎｅｓｅＥｎｃｅｐｈａｌｉｔｉｓｖｉｒｕｓＥ－ｇｌｕｃｏｐｒｏｔｅｉｎ￥ＨｕＪｕｎ（胡军）；ＭａＷｅｎｙｕ（马文煜）；ＨｕａｎｇＱｉｎｇｓｈｅｎｇ（黄庆生）...     

环氧酶-2抑制剂对关节炎大鼠小肠黏膜的影响

目的 探讨环氧酶-2抑制剂对关节炎大鼠小肠黏膜的影响。方法 将32只雄性SD大鼠随机分为空白对照组、造模对照组、空白给药组和造模给药组,造模对照组、造模给药组给予弗氏完全佐剂右后足跖注射,空白对照组、空白给药组注射等量生理盐水。1周后造模给药组、空白给药组给予选择性环氧酶-2抑制剂塞来昔布（溶于1%甲基纤维素）灌胃28 d,空白对照组、造模对照组给予等量溶剂。处死大鼠后观察小肠黏膜大体损伤、病理评分,酶联免疫吸附试验检测末段小肠前列腺素浓度。结果 造模对照组与造模给药组模型复制第7天的足周径比较,差异无统计学意义（P>0.05）,但两组分别与空白对照组和空白给药组比较,差异有统计学意义（P <0.05）,空白对照组与空白给药组比较,差异无统计学意义（P>0.05）。空白对照组与造模对照组小肠黏膜损伤面积比较,差异有统计学意义（P <0.05）,空白给药组与空白对照组比较,差异有统计学意义（P <0.05）。造模对照组、空白给药组和造模给药组组间小肠黏膜病理评分比较,差异无统计学意义（P>0.05）,且空白对照组与其他3组比较,差异有统计学意义（P &...     

Antibodies to squalene in recipients of anthrax vaccine

We previously reported that antibodies to squalene, an experimental vaccine adjuvant, are present in persons with symptoms consistent with Gulf War Syndrome (GWS) (P. B. Asa et al., Exp. Mol. Pathol 68, 196-197, 2000). The United States Department of Defense initiated the Anthrax Vaccine Immunization Program (AVIP) in 1997 to immunize 2.4 million military personnel. Because adverse reactions in vaccinated personnel were similar to symptoms of GWS, we tested AVIP participants for anti-squalene antibodies (ASA). In a pilot study, 6 of 6 vaccine recipients with GWS-like symptoms were positive for ASA. In a larger blinded study, only 32% (8/25) of AVIP personnel compared to 15.7% (3/19) of controls were positive (P > 0.05). Further analysis revealed that ASA were associated with specific lots of vaccine. The incidence of ASA in personnel in the blinded study receiving these lots was 47% (8/17) compared to an incidence of 0% (0/8; P < 0.025) of the AVIP participants receiving other lots of vaccine. Analysis of additional personnel revealed that in all but one case (19/20; 95%), ASA were restricted to personnel immunized with lots of vaccine known to contain squalene. Except for one symptomatic individual, positive clinical findings in 17 ASA-negative personnel were restricted to 4 individuals receiving vaccine from lots containing squalene. ASA were not present prior to vaccination in preimmunization sera available from 4 AVIP personnel. Three of these individuals became ASA positive after vaccination. These results suggest that the production of ASA in GWS patients is linked to the presence of squalene in certain lots of anthrax vaccine.     

Histopathological studies on the local reactions induced by complete Freund's adjuvant (CFA), bacterial lipopolysaccharide (LPS), and synthetic lipopeptide (P3C) conjugates

The inflammatory reactions following subcutaneous application of adjuvants revealed characteristic pathological patterns. The injection of complete Freund's adjuvant (CFA) resulted in the formation of large lipid deposits encircled by an inflammatory reaction and concentrically arranged collagen bundles. Bacterial lipopolysaccharide (LPS) caused granulomatous aggregations of mononuclear cells with thrombotic vessel occlusions. Inoculation of the lipopeptide adjuvants induced accumulation of mononuclear cells with only minimal fibrotic changes which were resolved after day 28. Lipopeptide conjugates based on the head group tripalmitoyl-S-glyceryl-cysteinyl-serin (P3CS) can thus be used as effective immunogens and adjuvants without long-term tissue damage.     

Immune effector cells induced by complete Freund's adjuvant exert an inhibitory effect on antigen-specific type 2 T helper responses

Background II has hecn well documented that environmental factors such as antigenpresenting cells and related cytokines could affect the development of T helper cells. Objective The purpose of this study is to investigate the effect of different adjuvants on T cell development. Methods Ovalbumin (OVA) combined with aluminum hydroxide (Alum) plus pertussis toxin (PT) or complete Freund's adjuvant (CFA) were used to sensitize mice; the production of IgG and IgE anli-OVA antibodies was then followed. In addition, OVA-specific proliferative responses and cytokine production by spleen cells were also investigated. Results The data showed that the adjuvants themselves could modify the pattern of immune response: (1) IgG_2a > anti-OVA antibody was higher in mice sensitized with OVA + CFA compared to that of mice sensitized with OVA + Alum + PT; (2) the ratio of IFN-γ/IL-4 produced by OVA-stimutated spleen cells was higher in mice sensitized with OVA + CFA than that of mice sensitized with OVA + Alum + PT; (3) increased percentage of γδ T cells was noted in the peritoneal exudate cells of OVA + CFA immunized mice; and (4) the immune response of mice sensitized wilh OVA + Alum+ PT was inhibited by the adoptively transferred ascitic cells from OVA + CFA immunized mice. Conclusion In general, the data suggested higher IgG2a and the ratio of IFN-γ/IL-4 was noted In mice sensitized with OVA + CFA. Further elucidation of the regulatory mechanism of allergen-specific T helper cells development and exploration of possible agents for inmiunotherapy might shed light on the management of atopic diseases.     

Hypersensitivity pneumonitis in rabbits. Modulation of pulmonary inflammation by long-term aerosol challenge with antigen

Immunized rabbits that were aerosol challenged for 2 to 3 wk with pigeon dropping extract, an etiologic agent of hypersensitivity pneumonitis, developed chronic pulmonary inflammation associated with cell-mediated immunity in bronchoalveolar cells. However, prolonged aerosol challenge for 12 wk resulted in the diminution of pulmonary inflammation (modulation) and the loss of demonstrable cell-mediated immunity. This was probably not due to loss of sensitized lymphocytes that mediated pulmonary inflammation. Furthermore, rabbits undergoing modulation when they were challenged with an unrelated antigen were refractory to the development of pulmonary inflammation for at least 9 wk. After this refractory period, animals reimmunized and aerosol challenged with pigeon dropping extract displayed an anamnestic response and produced pulmonary lesions that were strikingly similar to the histopathology of human hypersensitivity pneumonitis.