The intracellular ratio of the membrane to the secreted form of immunoglobulin M heavy chain is a measure of the developmental stage of B cell lymphomas

Tumors of B lymphocyte origin have been used as models for normal B cells “frozen” at particular stages of their development. Surface properties, amount, and intracellular location of immunoglobulin and the synthesis of J chain have all been used as indicators of developmental stages. Each requires special techniques or yields data that are difficult to compare from one experiment to the next. For these reasons, we have developed a metric for B cell development that is simple to perform and allows quick quantitative comparisons of cell lines. It has recently been established that the membrane (μ_m) and secreted (μ_s) forms of the IgM heavy chain differ at their extreme carboxy termini. The two proteins differ slightly in size and are easily distinguished when they are compared without their carbohydrate on sodium dodecyl sulfate (SDS) polyacrylamide gels. We have examined four mouse tumors derived from the B lymphocyte lineage whose phenotypes resemble late pre-B cells (internal μ only; uninduced 70Z/3), small B lymphocytes (high levels of surface IgM; LPS-induced 70Z/3, WEHI 231), lymphoblasts (both membrane and secreted IgM; WEHI 279.1), and plasma cells (copious IgM secretion; MOPC 104E). Despite the fact the 70Z/3 and WEHI 231 secrete no detectable IgM, all of the tumors synthesize at least intracellular forms of both μ_m and μ_s. The proportion of μ_m is stable and is characteristic of each tumor. The 70Z/3 cells and WEHI 231 cells synthesize about 75% of their total μ as μ_m; WEHI 279.1 cells synthesize about 30% and MOPC 104E cells about 5% of their total μ as μ_m. The population of LPS-stimulated B lymphocytes shows a similar progression during its differentiation. The proportion of μ_m correlates with other developmentally regulated parameters (Fc receptor, Ia and plasma cell antigen levels, and J chain) and can be used as a simple metric for comparison with developing B lymphocytes and determination of the developmental stage of a B cell tumor.     

Concomitant sertoli and leydig cell tumor of the testis: a case report

A rare intratubular gonadal stromal tumor was present in the testis of a 45-year-old man who was admitted to our hospital with the chief complaint of gradual enlargement of the left testis. Tumoral markers were negative and no extension was observed. The tumor comprised an intratubular mixture of two types of tumor cells with intercellular junctions: the predominant tumor cells were consistent with a Sertoli cell origin and cells comprising the minor population consistent with a Leydig cell origin. The patient is disease free after 6-month follow-up. The case is considered to be a testicular mixed tubular Sertoli-Leydig cell tumor. It highlights a rare type of primary tumor of the testis that features a good prognosis.     

细胞外ATP与肿瘤免疫

ATP是最重要的胞内代谢产物之一,也是一种重要的信号分子。研究发现,某些凋亡刺激能诱导肿瘤细胞内ATP释放到细胞外,这种释放到细胞外的ATP能促进吞噬细胞对凋亡细胞的吞噬,由此激发特异性抗肿瘤免疫杀伤效应,提示细胞外ATP在肿瘤免疫治疗中的潜在应用价值。本文就细胞外ATP在肿瘤免疫中的研究进展作一综述。     

Impact of histology on the treatment outcome of metastatic or recurrent renal cell carcinoma

Among 107 renal cell carcinoma (RCC) patients with histopathologic subtype diagnosis who were treated at Albert Einstein Cancer Center with cytokines over a 10-year period, seven patients had sarcomatoid histology, 63 had clear cell carcinoma, and 10 patients had mixed histology (sarcomatoid and clear cell). Regardless of their histology, patients with a disease free interval of 2 years or more had significantly better survival. None of the patients with sarcomatoid histology responded to therapy. However, several patients with mixed and clear cell histology achieved partial or complete responses following high dose interleukin-2 (IL-2) therapy. The median survival of patients with sarcomatoid histology was the shortest (13.8 months), whilst that of patients with mixed and clear cell histology was much longer (34.8 months and 39.1 months, respectively). This result was statistically significant in both univariate and multivariate survival analysis (P<0.001 andP<0.01, respectively). Patients with mixed and clear cell histology had no significant difference in survival, and their median survival combined was significantly longer than that of patients with sarcomatoid histology (P<0.0001 in univariate analysis,P<0.01 in multivariate analysis). This study suggests that survival with a diagnosis of RCC is predicted by tumor histology and disease free interval, and this impacts on the ability to respond to standard therapy. Patients with mixed and clear cell histology respond to cytokine therapy. Other therapies should be sought for patients with sarcomatoid RCC.     

综述:慢性炎症对肿瘤干细胞的调控

大量研究已证实肿瘤干细胞是肿瘤耐药、复发和转移的根源.慢性炎症与肿瘤的发生和发展密切相关,肿瘤炎性微环境中的IL-6、IL-8、EGF等炎性因子和生长因子激活了肿瘤干细胞内NF-κB/Stat3信号通路,维持肿瘤干细胞的自我更新能力,从而促进肿瘤的生长和转移.深入研究肿瘤炎性微环境对肿瘤干细胞的调控机制,可以使我们找到潜在的治疗靶点,为攻克肿瘤带来新的思路和手段.     

共刺激分子与宫颈癌相关性的研究进展

共刺激分子是T细胞激活的第二信号,有促进T细胞生长、分化和细胞因子产生的正调控分子,也包括诱导和维持T细胞免疫耐受以至凋亡的负调控分子。将从这两方面对共刺激分子在肿瘤免疫,尤其在宫颈癌中的相关研究方面进行综述。     

SFRP1 CpG island methylation locus is associated with renal cell cancer susceptibility and disease recurrence

Loss of the secreted Fzd-related protein 1 (SFRP1) and concurrent alteration of the SFRP1/WNT pathway are frequently observed in human cancers such as in renal cell cancer (RCC). Whether methylation of a SFRP1 CpG island locus in normal human solid tissues is associated with increased tissue specific cancer risk has not been determined to date. Here we measure the cancer risk attributable to SFRP1 DNA methylation in renal tissue. Pyrosequencing of bisulfite treated DNA was used for a case-control study including 120 normal-appearing renal tissues of autopsy specimens and 72 normal-appearing tissues obtained from tumor adjacent areas, and a cross sectional study of 96 RCCs. Association of methylation with demographic risk factor age, clinicopathological parameters and course of patients was investigated. We show significant hypermethylation of a SFRP1 CpG island locus in normal-appearing renal tissues from RCC patients compared with normal-appearing autopsy kidney tissues. Inter quartile analysis revealed a 6-, 13- and 11-fold increased cancer risk for the second, third and fourth quartiles of methylation in the age matched subgroup of tissues (p = 0.001, p = 1.3E-6, p = 6.9E-6). Methylation in autopsy tissues increased with age and methylation in tumors was an independent predictor of recurrence free survival. SFRP1 DNA methylation, accumulates with age in normal-appearing kidney tissues and is associated with increased renal cancer risk, suggesting this CGI sub region as an epigenetic susceptibility locus for RCC. Our data underline the need to further analyze the tissue specific risks conferred by methylated loci for the development of human cancers.     

单个肿瘤细胞测序研究进展

肿瘤是机体在各种致癌因素作用下,遗传物质受损导致特定细胞失去对正常生长调控,引起其克隆性异常增生而形成的恶性赘生物。随着单细胞分离技术及单细胞测序技术日益成熟,单个肿瘤细胞全基因组测序已成为肿瘤研究的一个崭新的领域。该文就对单个肿瘤细胞的获取及单个肿瘤细胞测序研究进展进行综述。     

灵芝中有效成分灵芝酸的抑制肿瘤作用研究

本文采用了体外肿瘤细胞培养增殖抑制试验与体内肿瘤细胞抑制试验,结果显示灵芝酸在体外对肿瘤细胞株SW620、LS180、S180的增殖具有明显的抑制作用,体内抗肿瘤疗效试验显示灵芝酸对Lewis肺癌(足趾接种)具有一定的疗效,对荷Lewis肺癌的小鼠IL-2的生成及NK细胞的免疫活性均有一定的促进作用。因此可以认为灵芝酸通过直接细胞毒作用与激活免疫体系实现抑制肿瘤作用。     

Recent advances and hurdles in melanoma immunotherapy

Worldwide incidence of malignant melanoma has been constantly increasing during the last years. Surgical excision is effective when primary tumours are thin. At later disease stages patients often succumb, due to failure of metastasis control. Therefore, great efforts have been made to develop improved strategies to treat metastatic melanoma patients. In the search for novel treatments during the last two decades, immunotherapy has occupied a prominent place. Numerous early phase immunotherapy clinical trials, generally involving small numbers of patients each time, have been reported: significant tumour‐specific immune responses could often be measured in patients upon treatments. However, clinical responses remain at a dismal low rate. In some anecdotal cases, objective clinical benefit was more frequently observed among immune responders than immune non‐responders. This clearly calls for a better understanding of protective immunity against tumours as well as the cross talk taking place between tumours and the immune system. Here we discuss advances and limitations of specific immunotherapy against human melanoma in the light of the literature from the last 5 yr.