喉鳞癌微血管密度与颈淋巴结转移及病理临床分期的相关性研究

目的研究喉鳞癌微血管密度与颈淋巴结转移及病理临床分期的相关性。方法采用抗Ⅷ因子相关抗原的抗体标记肿瘤血管内皮细胞并测定喉鳞癌组织微血管密度。结果①颈淋巴结转移组喉鳞癌的微血管密度显著高于非转移组(32.1518±6.489∶18.0672±4.983,P<0.01);②喉鳞癌微血管密度大于均数组则颈淋巴结转移率显著增高(P<0.01);③病理临床分期晚期组喉鳞癌的微血管密度明显高于早期组(P<0.01)。结论喉鳞癌微血管密度可作为预测其颈淋巴结转移的一项指标。     

颅-面联合径路前颅底区肿瘤切除术

目的完整切除侵及前颅底区肿瘤,提高治愈率.方法采用颅-面联合径路,其中单用带血管蒂帽状腱膜-颅骨膜瓣4例,帽状腱膜-颅骨膜瓣加肋骨片或钛网板各2例修补颅底.8例未做颅底重建.结果肿瘤全切16例,无1例手术死亡、长期脑脊液漏或/和颅内感染,5例恶性肿瘤患者术后存活3～5年;3例存活1～2年;均未见肿瘤复发.另4例在2年内分别死于局部复发和远处转移,4例良性肿瘤患者术后随诊1～7年未见复发.结论颅-面联合径路前颅底区肿瘤切除术,具有术野大、显露清楚、安全可靠,有利于肿瘤整块切除.硬脑膜修补和颅底重建,可有效地防止脑脊液漏和颅内感染等并发症.     

CD44 enhances tumor formation and lung metastasis in experimental osteosarcoma and is an additional predictor for poor patient outcome

Formation of metastases in the lungs is the major cause of death in patients suffering from osteosarcoma (OS). Metastases at presentation and poor response to preoperative chemotherapy are strong predictors for poor patient outcome. The elucidation of molecular markers that promote metastasis formation and/or chemoresistance is therefore of importance. CD44 is a plasma membrane glycoprotein that binds to the extracellular matrix component hyaluronan (HA) and has been shown to be involved in metastasis formation in a variety of other tumors. Here we investigated the role of CD44 expression on OS tumor formation and metastasis. High CD44 expression, evaluated with a tissue microarray including samples from 53 OS patients and stained with a pan‐CD44 antibody (Hermes3), showed a tendency (p < 0.08) to shortened overall survival. However, nonresponders and patients with lung metastases and high CD44 expression had significantly poorer prognosis than patients with low CD44 expression. Overexpression of the standard CD44 isoform (CD44s) and its HA‐binding defective mutant R41A in osteoblastic SaOS‐2 cells resulted in HA‐independent higher migration rates and increased chemoresistance, partially dependent on HA. In an orthotopic mouse model of OS, overexpression of CD44s in SaOS‐2 cells resulted in an HA‐dependent increased primary tumor formation and increased numbers of micrometastases and macrometastases in the lungs. In conclusion, although CD44 failed to be an independent predictor for patient outcome in this limited cohort of OS patients, increased CD44 expression was associated with even worse survival in patients with chemoresistance and with lung metastases. CD44‐associated chemoresistance was also observed in vitro, and increased formation of lung metastases was found in vivo in SCID mice. © 2013 American Society for Bone and Mineral Research.     

Bone Microenvironment-Suppressed T Cells Increase Osteoclast Formation and Osteolytic Bone Metastases in Mice

Immunotherapies use components of the immune system, such as T cells, to fight cancer cells, and are changing cancer treatment, causing durable responses in some patients. Bone metastases are a debilitating complication in advanced breast and prostate cancer patients. Approved treatments fail to cure bone metastases or increase patient survival and it remains unclear whether immunotherapy could benefit patients. The bone microenvironment combines various immunosuppressive factors, and combined with T cell products could increase bone resorption fueling the vicious cycle of bone metastases. Using syngeneic mouse models, our study revealed that bone metastases from 4T1 breast cancer contain tumor-infiltrating lymphocyte (TILs) and their development is increased in normal mice compared to immunodeficient and T-cell depleted mice. This effect seemed caused by the TILs specifically in bone, because T-cell depletion increased 4T1 orthotopic tumors and did not affect bone metastases from RM-1 prostate cancer cells, which lack TILs. T cells increased osteoclast formation ex vivo and in vivo contributing to bone metastasis vicious cycle. This pro-osteoclastic effect is specific to unactivated T cells, because activated T cells, secreting interferon γ (IFNγ) and interleukin 4 (IL-4), actually suppressed osteoclastogenesis, which could benefit patients. However, non-activated T cells from bone metastases could not be activated in ex vivo cultures. 4T1 bone metastases were associated with an increase of functional polymorphonuclear and monocytic myeloid-derived suppressor cells (MDSCs), potent T-cell suppressors. Although effective in other models, sildenafil and zoledronic acid did not affect MDSCs in bone metastases. Seeking other therapeutic targets, we found that monocytic MDSCs are more potent suppressors than polymorphonuclear MDSCs, expressing programmed cell death receptor-1 ligand (PD-L1)⁺ in bone, which could trigger T-cell suppression because 70% express its receptor, programmed cell death receptor-1 (PD-1). Collectively, our findings identified a new mechanism by which suppressed T cells increase osteoclastogenesis and bone metastases. Our results also provide a rationale for using immunotherapy because T-cell activation would increase their anti-cancer and their anti-osteoclastic properties. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

p53 Expression in Gastric Cancer (Clinicopathological Correlation and Prognostic Significance)

For evaluation of the prognostic relevance ofp53 expression in gastric cancer, theimmunohistochemical tissue status of 133 primary gastriccancer patients was investigated for p53 expression andthe association between p53 tissue status andclinicopathological parameters was analyzed. P53immunoreactivity was detected in the nuclei of cancercells in 35 cases (26.3%). The nuclear p53immunoreaction was closely associated with tumor location, lymph nodemetastasis, and curability. Tumors with positive p53stain reactions frequently metastasized to lymph nodes(metastatic rate: 91.4%) in contrast to tumors with negative p53 stain reactivity (71.4%, P =0.021). Immunohistochemical analysis of primary gastriccancer appears to be an accurate and simple method ofscreening for p53 expression. In combination with common prognostic parameters, determination of p53tissue status might help to detect prognosticallyunfavorable subgroups of gastric cancerpatients.     

基质金属蛋白酶-7mRNA与胃癌淋巴结微转移的关系

目的 探讨检测胃癌淋巴结微转移的有效方法。方法 用逆转录聚合酶链反应(RT-PCR)检测基质金属蛋白酶-7(MMP-7)mRNA在24例胃癌94枚淋巴结中的表达，并与常规病理检查进行对比。结果 94枚淋巴结常规病理组织学检出癌转移54枚，MMP-7mRNA表达阳性78枚。MMP-7mRNA表达阳性而传统组织学检查阴性的28个淋巴结，再次切片有8枚发现癌转移。对5例淋巴结组织学检查阴性而MMP-7mRNA表达阳性的患者随访中发现，有2例分别在胃癌根治术后16个月和22个月发现肝转移。结论 RT-PCR法检测。MMP-7mRNA对胃癌淋巴结微转移的诊断有较高的敏感性，对判断预后和指导术后辅助治疗具有重要意义。     

肿瘤侵犯大血管的外科治疗

目的　探讨累及大血管的肿瘤切除及受侵犯血管的处理方法 ,以提高肿瘤的切除率及术后生存率。方法　总结 1998年 10月～ 2 0 0 4年 2月的 2 6例累及重要血管的肿瘤切除及血管重建的经验。结果　 2 6例患者均无术后人工血管感染 ,血肿形成等。获随访 2 3例 ,随访时间 2～ 65个月 ,平均 42 .8个月。术后随访分别行彩色超声或CT血管显影 (CTA )检查 ,5例胰头癌和 1例胆管癌患者下腔静脉、门静脉置换后 ,3例分别于术后 3～ 15个月并发癌栓形成 ,术后远期通畅率为 5 0 % ,肿瘤分别于术后 3～ 3 1个月复发。 7例盆腔和腹膜后肿瘤切除血管置换患者术后获随访 2年 ,1例复发 ,但血管通畅。 2例四肢肉瘤患者随访 1年未见复发 ,血管通畅。 11例颈部肿瘤切除、血管置换患者术后随访 3个月至 5年 ,目前血管通畅 ,肿瘤未见复发。结论　对累及重要血管的肿瘤患者行肿瘤切除并大血管切除重建手术是安全的 ,可明显提高切除率、降低复发率 ,延长存活时间。     

端粒酶活性在乳腺癌中的表达及临床病理学相关性研究

目的　探讨端粒酶活性在乳腺癌的诊断价值及其临床病理学相关性。方法　应用端粒酶ＰＣＲ 酶联免疫吸附法定量检测４０ 例乳癌,３１ 例乳腺良性病变和９ 例正常乳腺组织端粒酶活性,同时与硝酸银染色定性检测对比。结果　端粒酶在乳癌、乳腺良性病变、正常乳腺组织表达的阳性率分别为７０ ％ （２８／４０） ,２９ ％ （９／３１） 和０ ％ （０／９） 。按定量检测其ＯＤ值分别为０．６０３,０．２５８ 和０．０３,３ 组之间均有显著性差异（ Ｐ ＜ ０ ．００１） 。端粒酶活性在乳癌中心和癌旁组织分别为０．６０３ 和０．２９３（ Ｐ ＜ ０ ．００１） 。按ＴＮＭ 分期,Ⅲ期（０．７８０ ±０．３９４） 高于Ⅱ期（０．５１１ ±０．４４７）（ Ｐ ＜ ０ ．０５） 。ＰＲ 阴性组（０．７８６ ±０．４４７） 高于ＰＲ 阳性组（０．５０１ ±０．３９３）（ Ｐ ＜ ０ ．０５） 。结论　良、恶性乳腺肿瘤端粒酶活性有显著性差异,可作为乳癌诊断的辅助指标之一;端粒酶活性与临床分期和ＰＲ 受体相关,提示端粒酶可作为反映乳癌侵袭性和预后的指标。