Subpopulations of human T-lymphocytes. XIX. T-cells and T-cells with receptors for IgMFc (T mu), IgGFc (T gamma), or IgAFc (T alpha) in the peripheral blood and regional lymph nodes of patients with untreated breast cancer

Peripheral blood and regional lymph node mononuclear cells from 43 untreated patients with breast cancer were analyzed for the proportions of total T-cells and T-cells with receptors for the Fc portion of IgM (T mu), IgG (T gamma), or IgA (T alpha). Proportions of total T-cells and T mu cells both in peripheral blood and lymph nodes from breast cancer patients were comparable to those from health controls. The proportion of T gamma cells, however, was significantly (P less than 0.01) increased in the peripheral blood and lymph nodes from breast cancer patients as compared to that from controls. The proportion of T alpha in the peripheral blood was comparable; however, when compared to the number of T alpha cells in control lymph nodes, T alpha cells were increased (P less than 0.025) in the regional lymph nodes from patients with breast cancer. When data on the proportions of T-cells and T-cell subsets were analyzed according to the presence or absence of metastatic disease in the regional lymph nodes, the proportion of T gamma cells was significantly (P less than 0.025) higher in the peripheral blood from patients with metastatic disease than in patients with nonmetastatic disease. This study demonstrates an abnormality of T-cell subsets in the peripheral blood and the regional lymph nodes from patients with breast cancer. The significance of these observations is discussed.     

Lymphocyte function-associated antigen-1 and intercellular adhesion molecule-1 expression on B-cell subsets and the effects of splenectomy-experimental studies

There is an abundance of data dealing with recirculation of T cells in the rats, but relatively little is known about the traffic of B cells. The adhesion molecules expressed on the surface membrane are of great significance for recirculation of lymphocytes. However, very little is known about the expression of various adhesion molecules on B-cell subsets. Here we show that in normal rats various adhesion molecules are differentially expressed on B-cell subsets and that the level of their expression changes after the entry of B lymphocytes from the blood into the lymphoid tissues. In splenectomized rats, the surface expression of LFA-1 and ICAM-1 is selectively reduced on B-cell subsets in blood and lymph node, which is accompanied by a selective increase in the number of all B-cell subsets in the blood. The decreased surface expression of adhesion molecules results in faster migration of B lymphocytes through lymph nodes with subsequent accumulation of these cells in the blood.     

食管癌术中淋巴结化疗的临床研究

目的 淋巴结转移是影响食管癌患者预后的主要因素.淋巴结化疗(lymph node chemotherapy,LNC)采用吸附了化疗药物的载体可被淋巴结中巨噬细胞吞噬的原理实现淋巴结的“靶向化疗”.本研究探讨LNC在食管癌术中的运用价值,筛选LNC中的较优药物,并与同期静脉化疗对比.方法 选取2013-01-21-2013 10-23四川大学华西医院胸外科接受食管癌治疗的患者92例,采取单中心前瞻性半随机单盲对照研究.其中紫杉醇-纳米炭淋巴结化疗组(LNC by paclitaxel-carbon nanoparticles,LNP)、氟尿嘧啶纳米炭淋巴结化疗组(LNC by fluorouracil-carbon nanoparticles,LNF)各41例,按相应药物接受术中LNC;氟尿嘧啶静脉化疗组(venous chemotherapy by fluorouracil,VF)10例,接受术中氟尿嘧啶静脉化疗.光镜下观察注射部位及淋巴结内药物分布,比较各组淋巴结、血清相应药物浓度.结果 光镜下吸附了化疗药物的纳米炭未引起局部组织炎性细胞浸润及坏死,并可聚集于淋巴结皮质.LNP组淋巴结中紫杉醇药物浓度为2.16(3.25),高于血清浓度0.00(0.00),Z=5.579,P＜0.01.LNF组淋巴结中氟尿嘧啶药物浓度为0.44(1.07),也高于血清浓度0.00(0.31),Z=-3.069,P＜0.01.而VF组淋巴结药物浓度0.11(0.26)与血药浓度0.00(0.15)的差异无统计学意义,Z=-0.135,P-0.893.LNF组淋巴结内药物浓度0.44(1.07)比VF组0.11(0.26)高,H=94.500,P＜0.01.LNP组淋巴结内药物浓度2.16(3.25)高于LNF组0.44(1.07),H=351.000,P＜0.01,血清药物浓度0.00(0.00)则低于LNF组0.00(0.31),H=577.000,P＜0.01.结论 在食管癌术中,LNC可安全、有效地使化疗药物靶向进入并停留于淋巴结,在淋巴结转移疗效上可能优于同期静脉化疗.实施LNC时,优选对载体亲和力高的药物.     

Suppressor cell activity in melanoma-draining lymph nodes

We previously demonstrated that the cells of lymph nodes near to a melanoma respond well to stimulation by mitogens, alloantigens, and interleukin 2 than do nodes further away. In this study we examined suppressor T-cell activity in nodes at different distances from primary melanoma, using a concanavalin A (Con A) suppressor cell assay. Tumor-free regional nodes were classified as proximal, intermediate, and distal relative to primary melanoma. Lymph node lymphocytes (LNL) were stimulated with 50 micrograms/ml Con A for 48-72 h, inactivated, and then mixed with autologous peripheral blood lymphocytes. The peripheral blood lymphocyte-LNL mixtures were stimulated with phytohemagglutinin for 3 days. Proliferation was measured by [3H]thymidine uptake during the final 18 h of culture. In 13 patients, Con A-treated LNL from nodes near to tumor were more suppressive of the peripheral blood lymphocyte response to phytohemagglutinin than those from nodes located further from tumor. T-lymphocyte subset assessment before and after Con A treatment of LNL showed no significant changes in T4:T8 ratios. Con A-induced suppressor cells could be maintained in culture in the presence of recombinant interleukin 2 and retained their suppressive activity. LNL not exposed to Con A and maintained in culture with interleukin 2 did not show suppressor cell activity. Suppressor cell activity thus contributes to the weak immune reactivity of lymph nodes near to melanoma.     

pN1a甲状腺乳头状癌中央区淋巴结清扫数与临床转归的关系

背景与目的:甲状腺乳头状癌(papillary thyroid carcinoma,PTC)常发生颈部淋巴结转移,多见于颈部中央区.该研究旨在探讨转移淋巴结数小于等于5枚的pN1a PTC患者颈部中央区淋巴结清扫数与131I"清甲"治疗后临床转归的关系.方法:回顾性分析2012年2月—2014年12月北京协和医院收治的167例经术后病理证实存在1~5枚淋巴结转移的pN1a PTC患者的临床资料,均行全甲状腺切除或近全甲状腺切除联合中央区淋巴结清扫术.经过131I"清甲"治疗后中位随访26个月,将患者的临床转归根据美国甲状腺协会(American Thyroid Association,ATA)2015年发布的《成人甲状腺结节与分化型甲状腺癌诊治指南》分为:满意(excellent response,ER)、不确切(indeterminate response,IDR)、血清学反应欠佳(biochemical incomplete response,BIR)和影像学反应欠佳(structural incomplete response,SIR).计算不同淋巴结清扫数对应的累计ER率(以ERn表示,n为淋巴结清扫数,ERn为清扫数小于等于n枚淋巴结后达到ER的患者数占清扫数小于等于n枚淋巴结的总人数的百分比),分析中央区淋巴结清扫数与ERn的关系.结果:随着中央区淋巴结清扫数增多,ERn总体呈上升趋势,ER1、ER5、ER10和ER30分别为25.0%、66.7%、74.7%和79.1%,且n由1至10时ERn升高明显.n大于等于10的患者的满意率高于n小于10的患者,差异有统计学意义(85.7%vs 73.3%,P=0.05).多因素Logistic回归分析显示,中央区淋巴结清扫数大于等于10枚(OR=2.720,95%CI:1.052~7.033,P=0.039)、131I治疗前刺激性甲状腺球蛋白(stimulated thyroglobulin,sTg)水平(OR=0.955,95%CI:0.926~0.984,P=0.003)是影响ER的独立预后因素.结论:随着中央区淋巴结清扫数的增多,pN1a PTC患者131I"清甲"治疗后更易达到ER;对于淋巴结转移数小于等于5枚的pN1a PTC患者,中央区淋巴结清扫数大于等于10枚有助于其131I"清甲"治疗后达到ER.     

Inhibin/activin subunits (inhibin-alpha, -betaA and -betaB) are differentially expressed in human breast cancer and their metastasis

Inhibins (INH) are dimeric glycoproteins, composed of an alpha-subunit (INH-alpha) and one of two possible beta-subunits (INH-betaA or -betaB). Aims of this study were to determine the frequency and tissue distribution of INH-alpha, -betaA and -betaB in breast cancer tissue. Paraffin-fixed ductal carcinoma in situ (DCIS; n=7), invasive ductal carcinomas without lymph node metastases (IDC; n=8), infiltrating ductal carcinomas with their lymph node metastases (IDC/LN; n=8), primary ductal carcinomas with their subsequent recurrence (n=7) were analyzed by immunohistochemical means with monoclonal antibodies against inhibin-alpha, -betaA and -betaB subunits. INH-alpha was observed in DCIS (5/7), while its expression was significantly higher in DCIS than IDC (1/7; p<0.05) and IDC/LN (0/8; p<0.005) and recurrent breast cancer tissue (0/7; p<0.005). The INH-betaA subunit was also demonstrated in all DCIS cases with a significantly higher intensity compared to IDC (p<0.05), IDC/LN (p<0.01) and primary carcinoma with subsequent recurrence (p<0.05). INH-betaA expression was significant higher in primary tumors with subsequent recurrence compared to IDC/LN (p<0.05). The metastatic lymph nodes expressed the lowest inhibin-betaA compared to all other groups (p<0.01). INH-betaB was also demonstrated in all mammary carcinoma tissues, but without any statistical differences. The differential expression of INH-alpha in DCIS might suggest a function as a tumor suppressor in breast tissue, suggesting a useful marker for recognizing patients with subsequent risk of developing invasive ductal cancer. The higher INH-betaA expression in DCIS than invasive cancer suggests an important role in mammary carcinogenesis. Interestingly, primary breast tumor with a subsequent recurrence expressed a higher intensity of the inhibin-betaA subunit, suggesting an important role in metastatic pathogenesis, and utilization as a tumor marker. The immunoreactivity of inhibin-betaA was significantly higher in DCIS than invasive ductal carcinomas, suggesting an important role in mammary carcinogenesis. The metastatic lymph nodes expressed lower INH-betaA and -betaB than the primary tumor, which might be the cause of less differentiated and aggressive tumor cells within the primary tumor. Therefore, inhibin/activin subunits might be useful prognostic markers for breast cancer.     

B-cell malignancy and monoclonal gammopathy, and idiotype of cell surface and serum immunoglobulin

We studied cell surface membrane immunoglobulins (SmIg), intracytoplasmic Ig (CIg) and monoclonal Ig (M protein) in patients with the B-cell series malignancies; malignant lymphoma, chronic lymphocytic leukemia (CLL), Waldenstr?m's macroglobulinemia (WM), multiple myeloma (MM), and monoclonal gammopathy (MG) associated with Sj?gren's syndrome (SS). The patients were examined for idyotype (Id) determinants on the cell surface and in the cytoplasm of malignant cells as well as serum M proteins. Twenty-two patients had malignant lymphoma with monoclonal SmIg. The malignant cells of 11 patients contained CIg; four of these 11 patients had a small amount of serum M protein. SmIg of the IgM class was most frequent (12/22) and the lambda type light chain was predominant (kappa/lambda ratio = 4/8). By means of rabbit anti-Id antisera prepared against M proteins, Id determinants were demonstrated on the cell surface and in the cytoplasm of malignant cells as well as in the serum M proteins, indicating that the malignant cells proliferated monoclonally producing monoclonal IgM on the cell surface and in the cytoplasm and secreting it to the serum. Six CLL patients were included in our series; one manifested monoclonal IgM in the serum. The Id determinants of M protein was detected on the cell surface and in the cytoplasm of pathologic cells in the peripheral blood. Eight of ten WM patients were examined for SmIg; all had monoclonal SmIg on the surface of cells from peripheral blood or bone marrow. Id determinants were detected on the cell surface and in the cytoplasm of malignant cells in four WM patients. There were 42 patients with MM; 10 of them were examined for SmIg and three of these had monoclonal SmIg on plasma cells derived from the bone marrow. By immunofluorescent and mixed rosette methods, Id-bearing B (0-20%) and T cells (0-2%) were identified in the peripheral blood of MM patients who had no plasma cells in the peripheral blood. Our findings suggest that a monoclonal change may occur at the B-cell level and that Id-bearing T cells may exist as regulatory T cells. Ten SS patients had M proteins. Non-IgM class M proteins (2 IgG and 4 IgA) were more frequent than the IgM class (3 IgM). Four M proteins with rheumatoid factor (RF) activity were found among these 10 M proteins.(ABSTRACT TRUNCATED AT 400 WORDS)     

甲状腺癌中Bax、Survivin及Livin的表达及意义

目的 探讨甲状腺癌中B细胞淋巴瘤-2相关X蛋白(Bax)、生存素(Survivin)及Livin的表达及意义.方法 采用免疫组化法检测82例甲状腺癌组织及相应癌旁正常组织中Bax、Survivin及Livin的阳性表达,分析三者与临床病理参数的关系.结果 甲状腺癌组织中Bax的阳性表达率明显低于癌旁正常组织(P﹤0.001),Survivin及Livin的阳性表达率明显高于癌旁正常组织(P﹤0.001).Ⅲ~Ⅳ期甲状腺癌患者的Bax阳性表达率明显低于Ⅰ~Ⅱ期患者,有淋巴结转移患者的Bax阳性表达率明显低于无淋巴结转移患者(P﹤0.01).Ⅲ~Ⅳ期甲状腺癌患者的Survivin及Livin阳性表达率明显高于Ⅰ~Ⅱ期患者,有淋巴结转移患者的Survivin及Livin阳性表达率明显高于无淋巴结转移患者(P﹤0.01).甲状腺癌组织中Bax与Survivin的表达呈负相关(r=-0.435,P﹤0.01),Bax与Livin的表达也呈负相关(r=-0.551,P﹤0.01),Survivin与Livin的表达呈正相关(r=0.738,P﹤0.01).结论Bax在甲状腺癌组织中低表达,Survivin及Livin在甲状腺癌组织中高表达,并与TNM分期及淋巴结转移密切相关,三者联合检测可能成为甲状腺癌预后的参考指标.     

The role of 18F-fluoro-2-deoxy-D-glucose positron emission tomography (18F-FDG-PET) in the diagnosis of recurrence and lymph node metastasis of cervical cancer

The usefulness of positron emission tomography with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG-PET) in diagnosing recurrence and lymph node metastasis of uterine cervical cancer was evaluated as a preliminary study. The FDG uptake of 13 cervical cancer patients, including 4 patients with recurrence, was evaluated. The FDG uptake of the cervices of 5 patients who underwent PET studies for non-cervical tumors were used as control. In 2 patients who had undergone radical hysterectomy, we compared the diagnosis of lymph node metastasis based on FDG-PET and magnetic resonance imaging. The FDG uptake in the 9 primary cervical cancers was greater than that in normal cervices (p=0.025). Examination of the 4 recurrent tumors revealed a higher FDG uptake than that in normal cervices (p=0.0022). Metastatic lesions in lymph nodes showed an accumulation of FDG on the PET scan. In conclusion, FDG-PET may be an effective diagnostic tool for detecting recurrence and lymph node metastasis of uterine cervical cancers.     

胃癌细胞增殖活性与脉管转移及预后关系的探讨

目的探讨胃癌细胞溴化脱氧脲嘧啶核苷（BrdUrd）标记指数（LI）、G2／M期细胞比率（G2／MPF）、DNA含量与胃癌淋巴管侵袭、淋巴结转移、静脉侵袭及预后之间的关系。方法用BrdUrd／DNA双参数流式细胞术（FCM）检测60例胃癌新鲜标本。碘化丙啶（PI）用于检测细胞DNA的荧光探针,抗BrdUrd单克隆抗体用于掺入DNA中的BrdUrd探针。荧光标记的羊抗鼠抗体用于第二抗体。用体外标记BrdUrd法检测S期比率,同时检测DNA倍体和G2／MPF。结果淋巴管侵袭阳性者BrdUrd LI和G2／MPF均明显高于阴性者（P〈0．01）,二者5年生存率差异有统计学意义（P〈0．01）。淋巴结转移阳性者BrdUrd LI和G2／MPF较阴性者明显增高（P〈0．01）,二者5年生存率差异有统计学意义（P〈0．01）。异倍体癌淋巴结转移阳性者明显增高（P〈0．05）,二倍体癌的5年生存率较异倍体癌明显增高（P〈0．05）。淋巴结多数转移者（〉5个）的BrdUrd LI较无转移者（P〈0．01）和少数转移者（1～4个）明显增高（P〈0．05）,G2／MPF较无转移者明显增高（P〈0．01）;淋巴结少数转移者较无转移者的G2／MPF明显增高（P〈0．05）,淋巴无结转移、少数转移和多数转移者之间比较,其5年生存率差异有统计学意义（P〈0．01）;异倍体癌淋巴结多数转移者明显增高（P〈0．01）。静脉侵袭阳性的G2／MPF较阴性者明显增高（P〈0．01）。结论胃癌细胞BrdUrd LI、G2／MPF、DNA含量和脉管侵袭与胃癌预后有一定的关系。     

Functional and surface phenotype study of lymphocyte subsets in peripheral blood and lymph nodes of breast cancer patients

In an attempt to identify lymphocyte subsets possibly involved in the response to malignant cells, we have studied the lymphocyte surface phenotype by using a panel of monoclonal antibodies on both peripheral blood lymphocytes (PBL) and histologically proven metastatic and nonmetastatic (i.e., "hyperplastic") axillary lymph node lymphocytes (LNL) from eight breast cancer patients. Furthermore, we carried out a functional study by evaluating the response to polyclonal mitogens of the PBL and of the LNL of the same patients. A group of 30 healthy subjects, age and sex matched, were selected as controls for PBL. Six of them, who underwent surgery for nonneoplastic conditions, were selected as controls for LNL. The responsiveness of breast cancer patients' PBL to polyclonal mitogens phytohemagglutinin (PHA) and concanavalin A (Con A) was significantly lower as compared with the control response. The responsiveness of breast cancer patients' metastatic LNL was not different from control LNL for PHA, and it was lower than control LNL for Con A, while the responsiveness of the same metastatic LNL was higher than that of nonmetastatic (i.e., hyperplastic) LNL of patients. Furthermore, the response of hyperplastic LNL was always lower than that of control LNL. The responsiveness of patients' PBL was always lower than that of metastatic LNL, while the responsiveness of patients' PBL vs. hyperplastic LNL was at variance. Regarding the surface phenotype of PBL, there was no difference between those of breast cancer patients and controls concerning the T-cells subsets, while the Leu 7, CD 21 and DR antigens were significantly higher among the breast cancer patients. No significant differences were found between patient metastatic and hyperplastic LNL or between control LNL and patient metastatic or hyperplastic LNL, respectively; only the CD 4 antigen was higher in metastatic than in hyperplastic LNL. A comparison of this surface phenotype between PBL and either metastatic or hyperplastic LNL of breast cancer patients showed values almost constantly significantly higher for PBL vs. either metastatic or hyperplastic LNL, respectively. The results of our study suggest that there is no change in the local-regional immunocompetent cell subsets that may be related to metastasis of breast cancer to regional nodes and to the progression of disease and that circulating T cells in breast cancer include cells expressing activation markers but not showing significant changes in the proportion of entire subpopulations.     

Detection of hematogenic and lymphogenic tumor cell dissemination in patients with medullary thyroid carcinoma by cytokeratin 20 and preprogastrin-releasing peptide RT-PCR

Despite an extensive surgical approach only 50% of the patients with medullary thyroid carcinoma (MTC) are biochemically cured. The failure to cure a larger number of patients is a result of the early dissemination of MTC. The present study evaluates two RT-PCR based assays for the detection of disseminated tumor cells in blood, bone marrow and lymph node samples of patients with MTC. Frozen tissue and blood samples of 19 patients with MTC and 61 cervical lymph nodes of these patients were obtained intraoperatively during thyroidectomy and lymphadenectomy. Preoperative bone marrow samples were obtained from 8 patients with MTC. An expression of CK20 and preproGRP was found in all MTC tissue samples. Using CK20-PCR, disseminated MTC cells were detected in 67% of the cervical lymph nodes of patients with MTC, compared to 72% involved lymph nodes, detected by preproGRP-PCR. In 16 of 61 nodes (26%) each PCR-system detected disseminated tumor cells in histologically tumor-free lymph nodes. Disseminated tumor cells were detected with CK20-PCR and preproGRP in 5 of 18 (28%) preoperative blood samples, each. The detection of a hematogenic tumor cell dissemination by preproGRP correlated significantly with the tumor stages (p = 0.019). Circulating MTC cells were found in 3 of 8 bone marrow samples with CK20-PCR, compared to 1 of 8 samples with preproGRP-PCR. Both PCR assays are highly sensitive to detect disseminated MTC cells in blood, bone marrow and lymph node samples. Our results of disseminated MTC cells in 26% of histologically tumor-free cervical lymph nodes and in 28% of the blood samples of patients with MTC might therefore explain the low biochemical cure rates.     

Cytokine-containing gelfoam implants at a postsurgical tumor excision site to stimulate local immune reactivity

We previously demonstrated increased numbers of CD34(+) progenitor cells in the peripheral blood of tumor bearers. Also demonstrated was the feasibility of chemoattracting these cells by sponge implants containing VEGF. The present study used a murine Lewis lung carcinoma (LLC) model to test if CD34(+) cells that are chemoattracted to a tumor excision site can be differentiated in situ into dendritic cells and whether this leads to increased local immune reactivity. After surgically excising established LLC tumors, mice received at the excision site gelatin sponge implants containing VEGF to chemoattract CD34(+) cells, and/or GM-CSF plus SCF to induce CD34(+) cell differentiation into dendritic cells. In some studies, lysates of GFP-transfected LLC cells (LLC(GFP)) were also included in the implants as a source of tumor antigen. After 2 weeks, implants and local lymph nodes were removed and analyzed. Implants containing VEGF, GM-CSF/SCF or VEGF/GM-CSF/SCF had a higher proportion of CD34(+) cells compared to control implants. However, the number of dendritic cells was higher in implants containing GM-CSF/SCF or VEGF/GM-CSF/SCF than those containing either VEGF or diluent. Regional lymph node from mice containing GM-CSF/SCF or VEGF/GM-CSF/SCF implants showed increased dendritic cell levels. However, when lysates from LLC(GFP) were added to the implants, the highest proportion of dendritic cells associated with GFP was in lymph nodes of mice containing GM-CSF/SCF implants. Lymph node cells from mice with GM-CSF/SCF or VEGF/GM-CSF/SCF had a higher level of proliferation and IFN-gamma secretion in response to in vitro LLC lysate challenge, with the greatest response being from lymph node cells of mice with GM-CSF/SCF implants. These results suggest the feasibility of using GM-CSF/SCF-containing implants to increase dendritic cell levels, uptake of tumor antigens, trafficking to lymph nodes and stimulation of immune reactivity at tumor excision sites with residual tumor.     

Adjuvant hormone treatment and chemotherapy in postmenopausal women with operable breast cancer: a retrospective analysis.

Two hundred consecutive postmenopausal women with operable breast cancer and metastatic axillary nodes were treated during the period January - December 1981 with adjuvant chemotherapy (CMF) or hormonal treatment (tamoxifen). The distribution of receptor status (estrogen or progesterone), number of axillary metastatic nodes (less than = 3 or greater than 3), surgical treatment and size of the primary tumor were homogeneous in both groups. Receptor status and number of axillary lymph nodes were correlated with adjuvant treatment efficacy. Ten-year disease-free survival (DFS) was higher in the TAM-treated (72%) than in the CMF-treated group (52%) (p less than 0.01). In patients with less than = 3 axillary metastatic nodes, those treated with TAM had a higher DFS rate than those treated with CMF (75% vs 59%, p less than 0.01). There was no difference in DFS between CMF-and TAM-treated groups within the greater than 3 metastatic lymph node patients. In ER + primary tumors, DFS was higher in the subset treated with TAM (62%) than with CMF (51%) (p less than 0.05), whereas no difference in DFS was observed in ER- patients between the two treatment groups. Considering the TAM group, DFS was better (p less than 0.01) for ER+ cases than for ER- cases only at 5 years of observation. In the CMF group, DFS was not influenced by ER status. PgR content did not affect DFS in either adjuvant treatment group.     

Neoadjuvant therapy changes the lymphocyte composition of tumor-draining lymph nodes in cervical carcinoma

BACKGROUND: The objective of the current study was to illustrate the influence of neoadjuvant therapy on the local immune response in patients with cervical carcinoma. METHODS: Uninvolved tumor-draining lymph nodes (TDLN) (n=158 lymph nodes), including internal, external, and common iliac lymph nodes as well as obturator, presacral, and aortic lymph nodes from 15 nontreated (NT) patients, 4 chemotherapy (CT)-treated patients, and 19 chemoradiation (CR)-treated patients, were analyzed for lymphocyte subset distribution and for the proliferative response of T cells to polyclonal activation and interferon-gamma (IFN-gamma) production. Lymphocyte subsets in peripheral blood also were assessed. RESULTS: TDLNs from CR-treated patients contained higher proportions of CD8+ cells and natural killer cells than NT and CT-treated patients (P values ranged from <0.05 to <0.01). TDLNs from CR-treated patients were enriched in activated-type CD4+ cells (HLA-DR+, CD134+, CD62L-, and CD25+ at an intermediate expression level; P values ranged from <0.05 to <0.01) and activated-type CD8+ cells (CD62L-, P<0.001) compared with NT patients. Concomitantly, there was a reduction in the proportion of na?ve-type CD4+ and CD8+ cells (CD45RA+/CD62L+) (P<0.01 and <0.05, respectively). CR treatment increased the proportion of both CD4+ and CD8+ cells prone to produce IFN-gamma. All TDLNs contained suppressive CD4+ T regulatory (Treg) cells (CD25+ and CD152+ at a high expression level) whose frequency and suppressive activity was not influenced by the treatment. Therapy-induced changes in TDLN were mirrored only in part by respective alterations in peripheral blood. CONCLUSIONS: To our knowledge, the current study is the first to show that neoadjuvant therapy produces an enhancing effect on the immune competency of TDLNs from patients with cervical carcinoma.     

血管内皮生长因子-C mRNA的表达与食管鳞癌临床病理特征的关系

目的 探讨血管内皮生长因子-C(VEGF-C)mRNA的表达与食管鳞癌临床病理特征的关系.方法 采用实时荧光定量逆转录多聚酶链反应(QRT-PCR)法,测定59例食管癌和正常黏膜中VEGF-C mRNA的表达.结果 食管癌组织中VEGF-C mRNA表达显著高于正常黏膜(6.30和2.81,P=0.02),淋巴结转移者的VEGF-C mRNA表达显著高于无转移者(10.11和4.15,P=0.04),转移淋巴结≥4枚患者的VEGF-C mRNA表达显著高于<4枚的患者(62.19和6.30,P=0.01),转移淋巴结组≥3组患者的VEGF-C mRNA表达显著高于<3组的患者(18.98和4.92,P=0.04),Ⅱb+Ⅲ+Ⅳ期患者的VEGF-C mRNA表达显著高于Ⅰ+Ⅱa期患者(9.99和3.80,P=0.03),颈淋巴结转移与区域淋巴结转移患者的VEGF-C mRNA表达无统计学意义.Logistic多元回归分析显示,VEGF-C mRNA高表达是食管癌淋巴结转移的独立危险因素(P=0.01).单因素和多因素分析均显示,EGFR-C mRNA表达与食管鳞癌患者的预后无关,而淋巴结转移组数是食管癌预后的独立危险因素(P<0.01).结论 VEGF-C mRNA的表达与食管鳞癌淋巴结转移密切相关,在食管鳞癌的淋巴结转移中起着非常重要的作用.     

B-lymphocytes and T-lymphocytes in three types of bovine lymphosarcoma.

Lymphoid cells of peripheral blood, lymph nodes, and thymus from clinically normal cattle, cattle infected with bovine leukemia virus (BLV), and cattle with lymphosarcoma were characterized for T- and B-cell surface markers. B-cells were detected by the erythrocyte-antibody-complement (EAC) rosette test and the surface immunoglobulin (sig) immunofluorescence assay. Peripheral blood from BLV-infected cattle had a higher than normal percentage of B-cells by both EAC rosette and sig immunofluorescence assays. Lymphoid cells from tumorous lymph nodes of cattle with the adult type of lymphosarcoma had a higher than normal percentage of sig-bearing cells, but in the same cell preparation the EAC rosette-positive cells were fewer than sig-positive cells. T-cells were detected by the erythrocyte rosette test. The percentage of T-cells by this test in lymph nodes of adult type lymphosarcoma was lower than that in normal cattle. A distinctly lower than normal percentage of lymphocytes could be characterized as either B- or T-cells in lymph nodes thymus, and peripheral blood from the calf type and thymic type of lymphosarcoma.     

Significance of lymph node micrometastasis in pN0 hilar bile duct carcinoma.

AIMS: To examine micrometastasis in node-negative hilar bile duct carcinoma (HBDC) using an immunohistochemical method and evaluated the clinical significance. METHODS: Four hundred and twenty three regional lymph nodes from 28 patients with node-negative HBDC who had undergone a resection were immunostained with an antibody against cytokeratins eight and 18 (CAM 5.2). RESULTS: Lymph node micrometastasis was detected in 11 of the 28 patients and 14 of the 423 lymph nodes. Lymph node micrometastasis was significantly correlated with the pT classification (p=0.03), the histopathological grading (p=0.01) and venous invasion (p=0.05). The 5-year survival rate of the patients with lymph node micrometastasis was 21.8%, as opposed to 66.5% in the patients without micrometastasis. Patients with micrometastasis showed a significantly poorer survival rate than those without micrometastasis (p=0.02). CONCLUSION: The results suggest that immunohistochemically detected lymph node micrometastasis has an impact on the outcome in HBDC.     

Blood lymphocyte counts with subset analysis in operable breast cancer. Relation to the extent of tumor disease and prognosis

Blood lymphocyte counts and various lymphocyte subsets, as defined by rosette tests, were examined in breast cancer patients and correlated to the extent of tumor disease and prognosis. One hundred sixty-six patients tested before or shortly after surgery were included. It was observed that the frequency of E-rosette-forming lymphocytes correlated to the development of distant metastases (P = 0.007) and survival (P = 0.022). A high frequency of E-rosette-forming cells was associated with a poor prognosis. The well-known prognostic value of clinical tumor stage and axillary lymph node involvement was also confirmed. A possible relation between the tumor disease and other immune variables was indicated by the finding that the frequency of EAC-rosette-forming lymphocytes (mainly B-cells) was reduced in patients with relatively large primary tumors. This relation was most pronounced in patients without axillary node involvement (P less than 0.01). In addition, it was observed that the blood lymphocyte counts were significantly higher in patients with three or more tumor-involved axillary nodes than in those with zero to two (P less than 0.005). Our results seem to stand in contrast to the generally held view that low lymphocyte counts and a low proportion of E-rosette-forming cells in the blood are associated with a large tumor burden and a poor prognosis.     

Studies on the use of membrane markers for the differential diagnosis of malignant lymphomas.

Lymphoid cells isolated from lymph nodes, spleen and the peripheral blood were examined using the rosette test with sheep erythrocytes (E), immunofluorescent staining of the surface immunoglobulins (SmIg) and the combined test (SmIg + E). The studies were performed on 48 patients with untreated non-Hodgkin lymphoma, 14 Hodgkin patients, 5 patients with lymphadenitis and on 132 controls. In the control group the following percentages of B-T lymphocytes were obtained: blood (n = 100); T-68 +/- 9, B-20 +/- 6, 0-11 +/- 7, BT-1 +/- 1, lymph nodes (n = 24): T-62 +/- 13, B-19 +/- 11, 0-18 +/- 8, BT-1 +/- 1, spleens (n = 8): T-45 +/- 9, B-33 +/- 9, 0-23 +/- 7, BT-1 +/- 1. In non-Hodgkin lymphoma lymph nodes a statistically significant increase of B and 'null' cells was noted in comparison to controls and to the Hodgkin lymphoma group. The characteristics of the Hodgkin nodes did not differ significantly from controls. After arranging the non-Hodgkin lymphomas according to the Kiel classification it was observed that the low-grade malignant lymphomas subtype most often an immunological 'B type' and 'mixed B/0' type was present whereas the high-grade malignant lymphoma group showed a distinct majority of 'null' cells. It was concluded that the surface markers studied allow a differentiation in most cases between the non-Hodgkin lymphomas and other disorders of the lymphoid system. They are not sufficient to distinguish the subtypes of non-Hodgkin lymphomas but do give interesting information about the more exact nature of the disorder.