Inhibitory effects of TNP-470 in combination with BCNU on tumor growth of human glioblastoma xenografts

This study investigated the effect of TNP-470 in combination with carmustine (BCNU) on the growth of subcutaneously implanted human glioblastoma xenografts in nude mice.Human glioblastoma U-251 cells (1×10 7) were injected into 24 nude mice subcutaneously.The tumor-bearing mice were randomly divided into 4 groups on the seventh day following tumor implantation:TNP-470 group,in which TNP-470 was given 30 mg/kg subcutaneously every other day 7 times;BCNU group,in which 20 mg/kg BCNU were injected into peritoneal cavity per 4 days 3 times;TNP-470 plus BCNU group,in which TNP-470 and BCNU were coadministered in the same manner as in the TNP-470 group and the BCNU group;control group,in which the mice were given 0.2 mL of the mixture including 3% ethanol,5% acacia and 0.9% saline subcutaneously every other day 7 times.The tumor size and weights were measured.The tumor microvessel density (MVD) was determined by immunostaining by using goat-anti-mouse polyclonal antibody CD105.The results showed that on the 21th day following treatment,the volume of xenografts in the TNP-470 plus BCNU group was (108.93±17.63)mm 3,markedly lower than that in the TNP-470 group [(576.10±114.29)mm 3 ] and the BCNU group [(473.01±48.04)mm 3 ] (both P<0.01).And the xenograft volume in these 3 treatment groups was even much lower than that in the control group [(1512.61±470.25) mm 3 ] (all P<0.01).There was no significant difference in the volume of xenografts between the TNP-470 group and the BCNU group (P>0.05).The inhibition rate of the tumor growth in the TNP-470 plus BCNU group was (92.80±11.37)%,notably higher than that in the TNP-470 group [(61.91±6.29)%] and the BCNU group [(68.73±9.65)%] (both P<0.01) on the 21th day following treatment.There was no significant difference in the inhibition rate of tumor growth between the TNP-470 group and the BCNU group (P>0.05).The MVD of xenografts in the TNP-470 plus BCNU group was decreased significantly as compared with that in the TNP-470 group or the BCNU group (both P     

A New Protein Girdin in Tumor Metastasis

The phosphatidylinositol 3-kinase/Akt serine/threonine kinase system regulates multiple cellular processesthrough the phosphorylation of a great number of downstream substrates and has been recognized as an important pathway for signal transduction, and in cancer invasion and metastasis.1 Although it is accepted that Akt promotes the metastasis of human malignant tumors, the mechanisms of Akt function to promote cell migration remains to be elucidated. Girdin,     

Inhibitory effect of ginsenoside Rg3 on ovarian cancer metastasis

Background Ginsenosides are main components extracted from ginseng, and ginsenoside Rg3 is one of the most important parts. Ginsenoside Rg3 has been found to inhibit several kinds of tumor growth and metastasis. The present study was undertaken to investigate the effect of ginsenoside Rg3 on human ovarian cancer metastasis and the possible mechanism. Methods The experimental lung metastasis models of ovarian cancer SKOV-3 and the assay of tumor-induced angiogenesis were used to observe the inhibitory effects of Rg3 on tumor metastasis and angiogenesis. The effect of Rg3 on invasive ability of SKOV-3 cells in vitro was detected by Boyden chamber, and immunofluorescence staining was used to recognize the expression of matrix metalloproteinase 9 （MMP-9） in SKOV-3 cells. Results In the experimental lung metastasis models of ovarian cancer, the number of tumor colonies in the lung and vessels oriented toward the tumor mass in each ginsenoside Rg3 group, was lower than that of control group. The invasive ability and MMP-9 expression of SKOV-3 cells decreased significantly after treatment with ginsenoside Rg3. Conclusions Ginsenoside Rg3 can significantly inhibit the metastasis of ovarian cancer. The inhibitory effect is partially due to inhibition of tumor-induced an qioqenesis and decrease of invasive ability and MMP-9 expression of SKOV-3 cells.     

Advances in TCM Treatment for Metastasis of Tumors

As one of the basic biologic features of malignanttumors and a major cause leading to failure oftreatment and even death,metastasis has aroused agreat interest among the medical researchers.To date,convincing evidence is still lacking as to whethermetastasis could be controlled by surgery,radio-orchemotherapy.However,TCM measures have provedto be advantageous in improving the survival qualityand prolonging the survival period by decreasing therate of distant metastasis of tumors.The following isa brief summary on the advances in this field.     

Lymphoepithelioma-like carcinoma of the submandibular salivary gland: a case report

Carcinoma of the salivary gland is an uncommon disease, accounting for less than 1% of all head and neck malignant neoplasm.1 Lymphoepthelioma is a malignant tumor of epithelial origin showing varying amounts of reactive lymphocytic infiltrate. Lymphoepithelioma-like carcinoma （LELC） constitutes a significant proportion of salivary gland carcinoma in Chinese and Eskimo populations and is related to Epstein-Barr virus infection. Carcinoma of the salivary gland has a propensity for early lymphatic metastasis, and thus a swelling of cervical lymph nodes is occasionally the sole initial symptom. It is very vital to consider a multimodality approach including surgery, radiotherapy and chemotherapy for the treatment in the locally advanced disease.     

Intraspinal clear cell meningioma： a case report

Clear cell meningioma (CCM) is a recently described histologic subtype of meningiema. It has an aggressive clinical behavior, and is prone to local recurrence and distant metastasis. The most common locations of the tumor are the spinal canal and the cranial posterior fossa. We present a case of typical clear cell meningioma in the cauda equina detected by magnetic resonance imaging (MRI) and microscopy,     

Papillary thyroid microcarcinoma presenting as skull base metastasis

Papillary thyroid carcinoma （PTC） is the most common type of well-differentiated thyroid cancer and is considered to be a relatively indolent tumor in which distant metastasis and death are rare.The metastasis of PTC is usually to regional lymph nodes, especially the cervical and mediastinal nodes.     

Tumor immune microenvironment-modulated nanostrategy for the treatment of lung cancer metastasis

As one of the most malignant tumors worldwide, lung cancer, fueled by metastasis, has shown rising mortality rates. However, effective clinical strategies aimed at preventing metastasis are lacking owing to its dynamic multi-step, complicated, and progressive nature. Immunotherapy has shown promise in treating cancer metastasis by reversing the immunosuppressive network of the tumor microenvironment. However, drug resistance inevitably develops due to inadequate delivery of immunostimulants and ...     

Study on Proteomics in Hepatic Metastasis of Colorectal neoplasms

Colorectal cancer is one of the most frequent cancers in the world. Hepatic metastasis is the most common site metastatic disease and dominant cause of death in colorectal cancer patients. In the large majority of cases, cell dysfunction in CRC results from multiple rather than single, gene interactions, so to be able to predict occurrence of disease and treatment outcome, more studies on comparative proteomics are needed both in sporadic and in hereditary colorectal cancer. This article is about the proteomic study on hepatic metastasis of colorectal cancer which helps to identify the specific proteins that play important roles in hepatic metastasis. The study of protein molecules with their expressions correlated to the metastatic process would help to understand the metastatic mechanisms and thus facilitate the development of strategies for the therapeutic interventions and clinical management of cancer.     

Intra-cranial metastasis of gastrointestinal stromal tumor

With the evolution of immunochemical staining techniques and better imaging modalities with better image resolution and whole body coverage, gastrointestinal stromal tumor (GIST), the most common mesenchymal tumor of the gastrointestinal tract, is often encountered in clinical practice. Metastasis is common with malignant GIST and can be found in up to 50% of patients at presentation. Liver and peritoneum are the two most common sites of metastasis and accounted for 95% of cases. Lymphatics, bone and lung metastasis are rare. Malignant GIST with intracranial metastasis is even rarer, with only a few cases reported in the literature, and most of these had earlier metastasis elsewhere. Radiological features for GISTs are not specific but it does contribute to confirming early and accurate diagnosis of malignant GISTs by judging the tumor size, enhancement pattern and the invasion of adjacent structures. We report a case of a 26-year-old male with metastatic GIST to the liver and subsequently to the brain and skull vault. This is the first case reported in our locality and he is the youngest patient reported with this disease entity. The clinical progress, radiological features and the role of imaging will be discussed further in this paper. The radiological and clinical features of the primary tumor will specifically be addressed. The purpose of this paper is to enrich the current database of this rare disease entity and to alert both radiologists and clinicians about the imaging features of GIST with intracranial metastasis.

     

TNP-470与阿霉素联合使用治疗小鼠膀胱癌

目的观察血管形成抑制剂TNF-470与化疗药物阿霉素联合应用抑制小鼠膀胱癌的协同作用.方法分别予TNP-470、阿霉素、TNP-470 阿霉素治疗TN39膀胱癌荷瘤小鼠,观察肿瘤生长及血管形成、细胞凋亡情况.结果治疗后12 d,TNP-470、阿霉素及TNP-470 阿霉素治疗组抑瘤率分别为46.3%、21.4%及56.5%,TNP-470组微血管密度明显减少、凋亡指数增多,阿霉素组凋亡指数增多,TNP-470 阿霉素组凋亡指数进一步增加.结论TNP-470与阿霉素治疗小鼠膀胱肿瘤,有明显的抗肿瘤协同作用,其机理可能是通过抑制血管形成及化疗药物细胞毒性作用而促使肿瘤细胞凋亡进一步增加.     

Ad-PUMA联合SU5416对裸鼠胰腺癌生长和转移的抑制作用

目的：研究重组腺病毒（Ad）-PUMA联合SU5416对裸鼠胰腺癌生长和转移的抑制作用。方法：建立裸鼠胰腺癌AsPC-1细胞株原位移植瘤模型,将胰腺癌裸鼠随机分为4组,于模型的第14天,分别自腹腔注射生理盐水100μL（对照组,n=8）、Ad—PUMA3×10^8pfu／100μL（PUMA组,n=10）、SU5416制剂16mg／kg（SU5416组,n=9）和Ad—PUMA＋SU54163×10^8pfu／100μL＋SU541616mg／kg（联合组,n=10）。治疗2周后处死裸鼠,剖腹测量原位肿瘤瘤重、抑瘤率、肿瘤微血管密度、胰腺癌细胞凋亡指数,同时观察腹膜、肝脏及毗邻脏器转移和腹水情况。结果：对照组、PUMA组、SU5416组、联合组诱发肿瘤瘤重分别为（0．72±0．08）、（0．48±0．06）、（0．52±0．07）、（0．21±0．04）g,抑瘤率分别为0、28％、34％、71％,肿瘤微血管密度分别为21．4±2．7、20．2±2．5、8．3±1．6、3．8±1．0,凋亡指数分别为（2．7±1．8）、（13．7±3．4）、（5．5±3．7）、（20．6±8．6）％,腹膜转移率分别为87％、70％、33％、10％,肝转移率分别为75％、50％、22％、0,联合组与对照组比较差异有统计学意义（P均〈0．05）。结论：AdPUMA联合SU5416具有协同抗胰腺癌作用。     

TNP-470和MMC联合应用对鼠结肠癌生长和肝转移的作用

目的：研究O-(氨乙酰-氨甲酰基)烟曲霉醇（TNP-470）和丝裂霉素（MMC）联合应用对结肠癌生长和肝转移的抑制作用。 方法：建立裸鼠结肠癌的原位生长和肝转移模型,随机分为对照组、TNP-470组、MMC组及联合用药组（TNP-470+MMC）。 结果：4个组瘤重分别为(499±247)、(478±180)、(275±80)和（255±65）mg,肝转移率分别为87.5%、25.0%、75.0%和12.5%,与对照组比较联合用药组抑制作用最明显（P<0.01）,且治疗后各组裸鼠活动良好,无明显体重减轻。 结论：TNP-470与MMC联合应用对结肠癌的生长及肝转移的抑制有协同作用,且未加重TNP-470引起的体重减轻等毒副作用。     

血管生成抑制剂联合分化诱导剂治疗结肠癌肝脏转移的实验研究

目的:实验通过建立人LOVO细胞结肠癌裸鼠肝脏转移瘤模型,研究血管生成抑制剂(TNP-470)联合分化诱导剂(RA)抗结肠癌转移的效应,二者是否具有协同效果.方法:建立人LOVO细胞结肠癌裸鼠肝脏转移瘤模型,随机分为4组,模型建立后分组治疗,至治疗结束时处死裸鼠,检测肝脏转移率和肝转移结节数及肝脏转移瘤组织中血管内皮生...     

重组人血管内皮抑制素对结肠癌生长及肝转移抑制作用的研究

目的探讨重组人血管内皮抑制素(恩度)对小鼠结肠癌生长及肝转移的抑制作用。方法 40只小鼠建立结肠癌肝脏转移模型,随机分为对照组,恩度低浓度组、中浓度组、高浓度组,每组10只。各组给药浓度分别为0 mg/kg、2 mg/kg、4 mg/kg、8 mg/kg,于术后第2天腹腔注射给药,1次/d,共10 d。停止给药后2 d观察各组小鼠原发灶的大小、肝转移瘤的数量,检测原发灶的凋亡指数(AI)、肿瘤微血管密度(MVD)和血清VEGF浓度。结果各组的原发灶的体积平均数分别为1.230 cm3、1.198 cm3、1.125 cm3、0.891 cm3。高浓度组与对照组比较,脾脏种植瘤的体积明显缩小(P<0.05)。高浓度组的转移瘤数量明显少于低浓度组和对照组(P<0.05),低浓度组和中浓度组之间差异无统计学意义(P>0.05)。高浓度组原发灶的AI高于对照组(P<0.05)。中、高浓度组转移瘤的MVD计数明显低于对照组(P<0.05)。血清VEGF的浓度各实验组均低于对照组(P均<0.05)。结论重组人血管内皮抑制素能明显抑制结肠癌的生长和肝转移。     

蛇床子水提取液抑瘤作用的实验研究

目的 :研究蛇床子水提取液的体内抗肿瘤作用。方法 :通过 S180 肉瘤移植建立荷瘤小鼠模型 ,给予不同剂量蛇床子水提取液后观察 S180 荷瘤小鼠肿瘤生长曲线、血清唾液酸 (SA)、瘤重及小鼠生存天数的变化。结果 :蛇床子水提取液能明显抑制肿瘤生长 ,降低荷瘤小鼠血清 SA水平 ,0 .0 6mg/(g· d) ,0 .1 1 mg/(g· d)、0 .2 1 mg/(g· d)剂量组平均瘤重低于肿瘤对照组 (P<0 .0 5 ) ,抑瘤率依次为 2 3 .2 %、2 9.1 %和 2 4 .8%,且能延长荷瘤小鼠生存天数 (P<0 .0 1 ) ,动物生命延长率依次为 :2 6 .9%、3 4 .8%和 2 6 .6 %。结论 :蛇床子水提取液具有较强的抗肿瘤效应 ,有很好的利用前景 ,值得对其进行深入研究。     

Leptin及其受体的表达与肝癌血管生成、生长和转移的关系

目的　探讨 L eptin及其受体的表达与肝癌血管生成和肿瘤生长、转移的关系。　方法　应用免疫组织化学方法观察 95例原发性肝癌、6 0例肝硬化、40例正常肝组织 L eptin及其受体 (Ob- R)的表达情况 ,分析 L eptin、Ob- R与微血管密度 (MVD)及肿瘤细胞增殖指数的关系。　结果　肝癌细胞上 L eptin呈强阳性表达者 ,其 MVD明显高于弱阳性表达及阴性者 (P<0 .0 5 ) ,两者呈正相关关系 (r=0 .42 78,P<0 .0 5 ) ;肝癌血管内皮细胞中 L eptin阳性表达者的 MVD明显高于阴性者 (P<0 .0 1) ,呈正相关关系 (r=0 .42 19,P<0 .0 5 ) ,且与肿瘤转移倾向成正相关 (P<0 .0 1) ;肝癌细胞中 Ob- R表达与转移的发生呈正相关关系 (P<0 .0 1) ,在肝癌组织中也可见 Ob- R在血管内皮细胞中的表达。　结论　 L eptin在肝癌的血管生成及转移过程中可能起着重要的作用。     

Heparanase antisense oligodeoxynucleotide inhibits angiogenesis and metastasis of human mammary carcinoma cell xenografts in nude mice

Objective： To evaluate the inhibitory effect of heparanase antisense oligodeoxynucleotide （AS-ODN） on the angiogenesis and metastasis of human mammary carcinoma cell xenografts in nude mice. Methods： The AS-ODN complementary to the start codon region of heparanase mRNA and its control, scrambled nonsense oligodeoxynucleotide （NS-ODN） were designed and synthesized. A subcutaneous growth model and an acute hematogenous metastasis model of human mammary carcinoma were established in nude mice and were treated with ODNs. The heparanase expression in tumor was evaluated by RT-PCR and Western blot. The microvessel density （MVD） was measured by immunohistochemistry for factor VS. The tumor volume was calculated and lung metastatic nodules were counted. Results ： The heparanase expression, MVD, tumor volume and lung metastatic nodules in AS-ODN treated group were significantly decreased compared with that in NS-ODN treated group and that in PBS group （P〈0.01）. Conclusion ： Heparanase AS-ODN has significant inhibitory effect on the angiogenesis and metastasis of human mammary carcinoma cell xenografts in nude mice.     

贝伐单抗联合TNP-470治疗结肠癌的实验研究

目的观察贝伐单抗联合血管生成抑制剂TNP-470治疗裸鼠结肠癌移植瘤的疗效,二者是否有协同效果。方法随机将48只大肠癌裸鼠分为对照组(A组)、贝伐单抗组(B组)、血管生成抑制剂(C组)、贝伐单抗与血管生成抑制剂联合组(D组),A组于左侧腋部皮下注射0.9%生理盐水30mg/kg,B组于左侧腋部皮下注射贝伐单抗5mg/kg,C组于左侧腋部皮下注射血管生成抑制剂TNP-470 30mg/kg,D组于左侧腋部皮下注射贝伐单抗5mg/kg和TNP-470 30mg/kg,1次/d,连用14d,至治疗结束时处死裸鼠,测量皮下移植瘤的长短径,分析各组间肿瘤体积差异的显著性;测量皮下移植瘤重量,计算抑瘤率;用细胞凋亡检测试剂盒测定裸鼠移植瘤凋亡水平,免疫组化检测结肠癌转移瘤血管内皮生长因子(VEGF)的表达和肿瘤微血管密度(MVD)。结果各实验组肿瘤的生长明显受到抑制,裸鼠皮下移植瘤瘤重、抑瘤率,D组和A组、B组、C组比较差异均有统计学意义(P<0.01),且B组、C组和A组之间差异亦有统计学意义;B、C、D组均可诱导移植瘤的凋亡,且差异有统计学意义;D组中的VEGF表达及MVD计数较A、B、C组均明显降低,差异有统计学意义。结论贝伐单抗与血管生成抑制剂TNP-470联合治疗结肠癌裸鼠皮下移植瘤比贝伐单抗或TNP-470单药治疗具有更强的抑瘤作用,二者联和应用,抗肿瘤效应明显增强。