Interactions between normal and tumoral tissues at the boundary of human anterior pituitary adenomas

We studied the boundary between adenoma and peritumoral anterior pituitary tissues in order to understand their mutual interactions during tumour progression. We selected 18 adenomas of different secretory type, grade and invasiveness in which fragments of peritumoral anterior pituitary were still attached to the adenoma. Immunohistochemistry was performed on serial sections with markers of the basement membranes (type IV collagen), the hormone-producing cells of the normal and neoplastic anterior pituitary, and the folliculo-stellate cells (S-100 protein). In passing from tumour to gland, localized areas of passive compression of the normal gland were seen in only 3 cases. In all the tumours, the boundary consisted partly or solely of a transitional zone characterized by the presence of enlarged cell-cords. Openings in the basement membrane of these enlarged cell-cords were seen in contact with the tumour tissue. Normal and neoplastic cells intermingled in the transitional zone. Normal residual cells could be seen in the central area of the tumour but no adenomatous cells were observed in the gland around the tumour. Folliculo-stellate cells were concentrated in the vicinity of the transition zone. These findings favour the existence of an active process of adenoma expansion within the normal parenchyma, without noticeable infiltration of tumour cells into surrounding gland.     

The use of luteinizing hormone releasing hormone agonists and antagonists in gynaecological cancers

The use of agonistic analogues of luteinizing hormone releasinghormone (LHRH) is an established therapy for hormone-dependentmetastatic pre-menopausal breast cancer. Their mechanism ofaction in this disease is the suppression of ovarian oestrogenproduction (medical castration). In the treatment of post-menopausalmetastatic breast cancer, LHRH agonists alsohave some effect,although minor, probably through a suppression of ovarian androgenproduction. Convincing evidence has been accumulated that LHRHanalogues can directly inhibit the proliferation of breast cancercells in vitro. The clinical impact of these findings, however,is still controversial. Experimental data and several pilotclinical trals suggest that in epithelial ovarian cancer andsex-cord-stromal tumours of the ovary, LHRH agonists might haveantitumour activity through the suppression of gonadotrophinsecretion (selective medical hypophysectomy). Phase III clinicaltrials, evaluating this hypothesis, are in progress. Directantiproliferative effects of LHRH analogues on epithelial ovariancancer cells have been demonstrated in vitro. In endometrialcnacer, experimental and early clinical results support theconcept of a direct antiproliferative activity of LHRH analogues.Recently, potent antagonistic analogues of LHRH, devoid of relevantside-effects have become available for clinical testing. Thesenew antagonists might be superior to agonistic LHRH analogueswith respect to the rapidity and efficacy of selective medicalhypophysectomy and medical castration. Modern LHRH antagonistsmight also permit a better exploitation of direct antitumoureffects. A further therapeutic improvement in gynaecologicaloncology might result from a combination of LHRH agonists orantagonists with other peptide hormone anlogues such as agonistsof somatostatin or antagonists of bombesin/gatrin releasingpeptide which have antitumour activity. Since 50% of breastcancers and 80% of epithelial ovarian cancers and endometrialcancers have high affinity binding sites for LHRH, cytotoxicLHRH analogues might provide a targeted chemotherapy, whichwould be more efficacious and less toxic than conventional regimens.     

Paraffin wax-embedded material as a source of DNA for the detection of somatic genetic changes

Loss of genetic material, corresponding to chromosomal deletions, has been detected in a wide range of tumours and may indicate the position of a tumour suppressor gene. In order to identify the position of such a gene more precisely, many tumour samples must be studied until a minimum consensus deletion is characterized. This process is particularly necessary for lung tumours in which the deletion in chromosome 3, seen with such high frequencies in all histological subtypes, is almost always large. We have recently described the use of the polymerase chain reaction (PCR) for restriction fragment length polymorphism (RFLP) analysis of DNA isolated from small bronchial biopsies of lung tumours. In this study we adapted this technique to allow genotyping of DNA isolated from paraffin wax-embedded material (PWEM) microdissected from glass slides. We have investigated 12 lung tumours at polymorphic loci on chromosome 3 and showed allelic loss in all samples. In adapting PCR–RFLP analysis for DNA isolated from PWEM, we have concentrated on those approaches which might be adaptable to routine clinical practice. Somatic genetic changes are now being identified in many tumour types, and this information is expected to be of diagnostic and prognostic significance.     

直肠癌转移与癌组织微血管密度的关系

目的:分析直肠癌组织的微血管密度(MVD)变化及其对癌转移的临床诊断价值。方法:采用免疫组织化学法,对72例手术切除直肠癌组织标本进行微血管标记;在光学显微镜下测定其MVD。将所有患者的临床及追踪随访资料与其手术标本的MVD数据进行统计分析。结果:有转移直肠癌组织的MVD高于无转移者(106.12±32.18vs84.26±27.13),差异有非常显著性意义。结论:直肠癌组织的MVD增加对诊断癌转移有一定的临床价值。     

Haplotype analysis of the BRCA2 9254delATCAT recurrent mutation in breast/ovarian cancer families from Spain

A frame-shift 9254del5 mutation was independently identified in 12 families, eleven of them with Spanish ancestors, in a BRCA2 screening performed in 841 breast and/or ovarian cancer families and in 339 women with breast cancer diagnosed before the age of 40 at different centers in France and Spain. We sought to analyze in detail the haplotype and founder effects of the 9254del5 and to estimate the time of origin of the mutation. Eight polymorphic microsatellite markers and two BRCA2 polymorphisms were used for the haplotype analyses. The markers were located flanking the BRCA2 gene spanning a region of 6.1 cM. Our results suggest that these families shared a common ancestry with BRCA2 9254del5, which is a founder mutation originating in the Northeast Spanish, with an estimated age of 92 (95% CI 56-141) generations.     

Influence of organ site and tumor cell type on MUC1-specific tumor immunity

We investigated the influence of organ-specific parameters on tolerance and immunity to human MUC1. C57Bl/6 mice (wild-type) and C57Bl/6 transgenic for MUC1 (MUC1.Tg) were challenged in the pancreas with Panc02-MUC1, a C57Bl/6-syngeneic pancreatic cancer cell line expressing human MUC1. Wild-type mice produced immune responses to MUC1 when presented on tumor cells growing in the pancreas; however, the responses to tumors in the pancreas were less effective than responses produced by tumor challenge at the s.c. site. Tumor immunity specific for MUC1 was produced in wild-type mice by two different procedures: (i) s.c. immunization of wild-type mice with a low dose of Panc02-MUC1 or (ii) adoptive transfer of spleen and lymph node cells harvested from wild-type mice previously immunized s.c. with Panc02-MUC1. This demonstrates that immune responses to MUC1 presented at the s.c. site can be detected and adoptively transferred. MUC1.Tg mice were immunologically tolerant to MUC1; however, some immunological protection against orthotopic challenge with Panc02-MUC1 was conferred by adoptive transfer of CD4+ and CD8+ T cells from wild-type mice. These results show that it is more difficult to produce immune responses to tumors growing at the pancreatic site than the s.c. site. Panc02-MUC1 cells growing in the pancreas were accessible to the immune system, and immune responses evoked by s.c. presentation of this molecule in wild-type mice were effective in rejecting tumor cells in the pancreas of both wild-type and MUC1.Tg mice. No effective anti-tumor immune responses against MUC1 were produced in MUC1.Tg mice.     

结肠癌患者血清叶酸含量分析

以放射免疫法测定36例结肠癌患者血清叶酸浓度,患者血清叶酸水平低于对照组(P＜0.05).这表明血清叶酸浓度与结肠癌的发生密切相关.调整饮食结构,改善低叶酸状态将会在预防结肠癌方面产生积极作用.     

CD44 stimulation down-regulates Fas expression and Fas-mediated apoptosis of lung cancer cells

Cytotoxic T lymphocytes (CTL) play a major role in the rejection of tumor cells, but tumor rejection does not always occur in vivo, indicating that defects in anti-tumor immune responses may be common. We here document a novel function for CD44--using lung cancer cells, we showed that stimulation of CD44 reduced Fas expression and Fas-mediated apoptosis: (i) lung cancer cells expressed high levels of CD44; (ii) engagement of CD44 on the cells by a specific antibody or fragmented hyaluronan reduced Fas expression; (iii) CD44 cross-linking reduced Fas-mediated apoptosis; (iv) stimulation of CD44 on lung cancer cells decreased IFN-gamma production by autologous CTL; and (v) CD44 stimulation prevented killing of lung cancer cells by autologous CTL. Based on these findings, we postulate a new concept--that interaction of CD44 on lung cancer cells with fragments of extracellular hyaluronan present in the surrounding extracellular matrix reduces Fas expression as well as Fas-mediated apoptosis of cancer cells. This leads to reduced susceptibility of the cells to CTL-mediated cytotoxicity through the Fas-Fas ligand pathway.     

支气管动脉超选择性介入治疗中晚期肺癌

目的 探讨支气管动脉超选择性介入化疗及栓塞治疗肺癌的疗效。方法 58例肺癌病人均行支气管动脉超选择性介入化疗栓塞术，观察治疗前后原发癌灶体积及最大直径与垂直直径的变化，比较肺CT影像学改变；观察栓塞剂用量与癌灶体积之间的关系；观察临床病征、介入并发症等情况，并进行分析。结果 支气管动脉超选择性介入化疗栓塞术治疗肺癌疗效显，术后原发癌灶的体积大多有不同程度缩小，肿瘤最大直径与垂直直径乘积缩小，降低50％以上的占89．66％，栓塞剂用量小，介入并发症出现率低，副反应轻。     

Epstein-Barr virus association with early cancers found together with gastric medullary carcinomas demonstrating lymphoid infiltration

Seven early gastric cancers obtained from patients also demonstrating Epstein-Barr virus (EBV)-positive gastric medullary carcinoma with lymphoid infiltration were investigated using a combined polymerase chain reaction (PCR) and in situ hybridization (ISH) approach. Sharing the same background mucosa as gastric medullary cancers, they comprised four intramucosal carcinomas, predominantly well-differentiated adenocarcinomas, and three submucosal carcinomas, histologically showing mixtures of well and poorly differentiated adenocarcinoma. In the three cases of submucosal carcinoma, the presence of EBV was proven by means of both PCR and ISH. However, not all cancer cells were positive for EBV on the basis of ISH examination, in contrast to the large series of gastric carcinoma with lymphoid infiltration previously investigated. All four mucosal carcinomas were EBV-negative. Lymphocyte-determined membrane antigen (LYDMA) monoclonality, performed by PCR, and latent membrane protein-1 (LMP-1) and Epstein-Barr virus (EBNA2) expression, assessed immunohistochemically, were negative in all seven cases. The results suggest that EBV becomes associated with gastric medullary carcinoma with lymphoid infiltration (GMCL) at a relatively early stage of the disease, shortly after the tumour has initially progressed to an invasive form, and plays some role in the manifestation as GMCL.