Long-term surgical outcomes of temporal lobe epilepsy associated with low-grade brain tumors

Phi, Ji Hoon,Kim, Seung-Ki,Cho, Byung-Kyu,Lee, Seo Young,Park, Su Yeon,Park, Sung-joon,Lee, Sang Kun,Kim, Ki Joong,Chung, Chun Kee Wiley Subscription Services, Inc., A Wiley Company 2009 Cancer Vol.115 No.24

<B>BACKGROUND:</B><P>Tumor-related temporal lobe epilepsy (TLE) has a high likelihood of medical intractability and requires surgical treatment. The aims of this study were to analyze the long-term surgical outcomes of and to present appropriate surgical strategies for tumor-related TLE.</P><B>METHODS:</B><P>The clinical data of 87 consecutive patients diagnosed with tumor-related TLE were analyzed. The median age at surgery was 22 years. Sixteen patients had a tumor confined to the amygdala or the parahippocampal gyrus, and 10 of them received a tailored lesionectomy without hippocampectomy. The surgical outcome was evaluated based on 3 aspects: seizure control, tumor control, and discontinuation of antiepileptic drugs (AEDs).</P><B>RESULTS:</B><P>The actuarial seizure and tumor control rates at the fifth year postoperatively were 79% and 90%, respectively. Seizure control was highly correlated with tumor control. The following factors were found to be significantly associated with poor seizure control: duration of epilepsy >10 years, presence of a remote focus on surface electroencephalography, and incomplete tumor removal. The actuarial AED maintenance rates were 47% at the second year and 11% at the fifth year. The median time to AED discontinuation was 22 months. A younger age at surgery was found to be significantly associated with an increased chance of AED discontinuation. Tailored resection focusing on the tumor resulted in a favorable outcome, even for tumors confined to the amygdala or the parahippocampal gyrus.</P><B>CONCLUSIONS:</B><P>Surgical treatment of tumor-related TLE resulted in long-term seizure control in the majority of patients. Maximal tumor removal can be recommended for tumor-related TLE. Cancer 2009. © 2009 American Cancer Society.</P>

Surgery of the Tumors in the Ventricular System

Hong, Sang-Won,Choi, Ha-Young,Koh, Eun-Jeong The Korean Neurosurgical Society 2006 Journal of Korean neurosurgical society Vol.39 No.1

Objective : The authors study on the clinical presentations and the surgical outcomes of the tumors in the ventricular system. Methods : 15 patients with ventricular tumor were studied. The clinical presentation, radiological findings, different surgical approaches, and outcome were analyzed. Tumors were classified into three groups based on their locations in MRI : lateral, third and fourth ventricle. Surgical methods were transcortical approach in eight patients, transcallosal approach in four, median suboccipital approach in two, and subfrontal approach in one. Gross total removal was achieved in 10 patients. Subtotal resections were performed in the rest. Glasgow outcome scale was used for evaluation of the surgical outcome. Results : Main clinical presentations were chronic headache in patients with the tumor in the lateral ventricular tumor and sudden onset of headache and consciousness change in patients with the tumor in the third and fourth ventricular tumor Development of hydrocephalus was more predominant in patients with the tumors in the third ventricle. Postoperatively, good outcome [Glasgow outcome scale IV, V] were in 73%, and better results was observed in patients with the tumors in the lateral ventricular tumor. The differences of outcome according to surgical approach were not recognized, even though it was not reliable statistically. Conclusion : In ventricular tumor, postoperative outcome is not good in patients with sudden development of headache, hydrocephalus, high grade tumor. Outcome is good in patients with the tumor in the lateral ventricle relatively. There is no difference in outcome according to the approach method to the tumors. And it is necessary to be aware of various approach methods to the tumors and anatomy surrounding the ventricle for avoidance of neurological complications.

Tumor vessel normalization by the PI3K inhibitor HS-173 enhances drug delivery

Kim, S.J.,Jung, K.H.,Son, M.K.,Park, J.H.,Yan, H.H.,Fang, Z.,Kang, Y.W.,Han, B.,Lim, J.H.,Hong, S.S. Elsevier 2017 Cancer letters Vol.403 No.-

Tumor vessels are leaky and immature, which causes poor oxygen and nutrient supply to tumor vessels and results in cancer cell metastasis to distant organs. This instability of tumor blood vessels also makes it difficult for anticancer drugs to penetrate and reach tumors. Numerous tumor vessel normalization approaches have been investigated for improving drug delivery into tumors. In this study, we investigated whether phosphoinositide 3-kinase (PI3K) inhibitors are able to improve vascular structure and function over the prolonged period necessary to achieve effective vessel normalization. The PI3K inhibitors, HS-173 and BEZ235 potently suppressed tumor growth and hypoxia, and increased tumor apoptosis in animal models. PI3K inhibitors also induced a regular, flat monolayer of endothelial cells (ECs) in vessels, improving stability of vessel structure, and normalized tumor vessels by increasing vascular maturity, pericyte coverage, basement membrane thickness, and tight-junctions. These effects resulted in a decrease in tumor vessel tortuosity and vessel thinning, and improved vessel function and blood flow. The tumor vessel stabilization effect of the PI3K inhibitor HS-173 also decreased the number of metastatic lung nodules in vivo metastasis model. Furthermore, HS-173 improved the delivery of doxorubicin into the tumor region, enhancing its anticancer effects. Mechanistic studies suggested that PI3K inhibitor HS-173-induced vessel normalization reflected changes in endothelial Notch signaling. Taken together, our findings indicate that vessel normalization by PI3K inhibitors restrained tumor growth and metastasis while improving chemotherapy by enhancing drug delivery into the tumor, suggesting that HS-173 may have a therapeutic value as an enhancer or an anticancer drug.

난소의 상피성 종양에서 신생혈관형성과 Cathepsin D 발현의 상관관계

박일수,배용철 대한부인종양 콜포스코피학회 2003 Journal of Gynecologic Oncology Vol.14 No.3

목적 : 악성종양의 진행과 전이과정에 관여하는 인자로 신생혈관형성 및 단백분해효소에 대한 관심이 높아지고 있으나, 이러한 인자들의 예후에 대한 중요성은 아직 확립되어 있지 않다. 본 연구에서는 양성, 경계성, 악성종양에서 신생혈관형성 유발인자인 VEGF의 발현도와 신생혈관수 및 Cathepsin D의 발현도와의 관계를 알아보고자 한다. 연구 방법 : 1997년부터 1999년까지 경북대학교병원에서 수술로 절제된 난소조직중 장액성 종양 41예와 점액성 종양 50예를 대상으로 면역조직화학적 염색을 이용하여 VEGF와 Cathepsin D의 발현 정도를 분석하였고, CD31에 대한 monoclonal antibody를 이용하여 미세혈관 수를 정량화 하였다. 장액성 종양은 양성 19예, 경계성 3예, 악성 19예였고, 점액성 종양은 양성 2예, 경계성 16예, 악성 14예였다. 결과 : 미세혈관 수, VEGF, Cathepsin D는 점액성과 장액성 모두에서 양성이나 경계성보다 악성에서 현저히 증가하였고, 특히 미세혈관 수는 재발한 1예와 사망한 1예에서 평균보다 높은 수치를 보였다. 그러나 임상인자인 병기, 종양크기 및 환자의 연령과는 통계학적 유의성이 없었다. VEGF 발현과 미세혈관 수 사이에는 유의한 상관 관계가 없으나, Cathepsin D와 VEGF, 신생혈관 수의 발현에는 유의한 상관관계가 있었다. 이는 종양의 혈관형성 에 있어 VEGF 이외에 다른 여러 가지 혈관형성인자 및 성장인자가 관여한다는 것을 보여준다. 결론 : 결론적으로 미세혈관 수, VEGF, 그리고 Cathepsin D의 발현은 난소종양 진행의 유용한 지표로서 여겨지나, 아직 예후에 대한 유의성이 확립되어 있지 않고, 추적기간이 짧아 앞으로 환자의 장기 생존률에 대한 지속적인 연구가 필요할 것으로 사료된다. Objective : Tumor angiogenesis and proteolysis have a role in tumor invasion and metastasis in various types of tumor. But the prognostic significance in ovarian epithelial tumors has not been established. In this study, we evaluate correlation of MVC, VEGF and Cathepsin D expression with progression in ovarian tumor. Methods : Formalin fixed tumor tissues from 41 cases of serous and 50 cases of mucinous tumors were analyzed for the expresssion of VEGF and Cathepsin D by immunohistochemical stain. The authors quantified microvessel counts (MVC) using monoclonal antibody for CD31. The serous tumors included 19 cases of benign, 3 cases of borderline and 19 cases of malignant tumors. The mucinous tumors included 20 cases of benign, 16 cases of borderline and 14 cases of malignant tumors. Results : MVC, VEGF and cathepsin D expression in malignant tumors were significantly higher than those in benign or borderline malignancy of both serous and mucinous tumors. One case of recurrence and another one case of death showed highly counted microvessels. But, there was no significant correlation as to FIGO stage, tumor size or patient’s age. There was no correlation between VEGF expression and MVC, however significant correlation was found between expression of Cathepsin D and VEGF and MVC. These results suggest that other angiogenic factors may affect in the regulation of angiogenesis. Conclusion : MVC, VEGF and Cathepsin D expression seems to be suggested as a useful indicator of progression in ovarian tumors. But, the prognostic significance cannot be fully established and additionally long-term follow up study for patient’s survival rate is needed.

Normalization of Tumor Vessels by Tie2 Activation and Ang2 Inhibition Enhances Drug Delivery and Produces a Favorable Tumor Microenvironment

Park, Jin-Sung,Kim, Il-Kug,Han, Sangyeul,Park, Intae,Kim, Chan,Bae, Jeomil,Oh, Seung Ja,Lee, Seungjoo,Kim, Jeong Hoon,Woo, Dong-Cheol,He, Yulong,Augustin, Hellmut G.,Kim, Injune,Lee, Doheon,Koh, Gou Y Cell Press 2016 CANCER CELL Vol. No.

<P><B>Summary</B></P> <P>A destabilized tumor vasculature leads to limited drug delivery, hypoxia, detrimental tumor microenvironment, and even metastasis. We performed a side-by-side comparison of ABTAA (Ang2-Binding and Tie2-Activating Antibody) and ABA (Ang2-Blocking Antibody) in mice with orthotopically implanted glioma, with subcutaneously implanted Lewis lung carcinoma, and with spontaneous mammary cancer. We found that Tie2 activation induced tumor vascular normalization, leading to enhanced blood perfusion and chemotherapeutic drug delivery, markedly lessened lactate acidosis, and reduced tumor growth and metastasis. Moreover, ABTAA favorably altered the immune cell profile within tumors. Together, our findings establish that simultaneous Tie2 activation and Ang2 inhibition form a powerful therapeutic strategy to elicit a favorable tumor microenvironment and enhanced delivery of a chemotherapeutic agent into tumors.</P> <P><B>Highlights</B></P> <P> <UL> <LI> ABTAA-induced Tie2 activation and Ang2 inhibition normalize tumor vasculature </LI> <LI> Tumor vessel normalization leads to enhanced blood perfusion and drug delivery </LI> <LI> Tumor vessel normalization lessens hypoxia, acidosis, tumor growth, and metastasis </LI> <LI> Tie2 activation favorably alters the tumor microenvironment and immune infiltration </LI> </UL> </P> <P><B>Graphical Abstract</B></P> <P>[DISPLAY OMISSION]</P>

Tumor-Derived Transforming Growth Factor-β is Critical for Tumor Progression and Evasion from Immune Surveillance

Li, Zheng,Zhang, Li-Juan,Zhang, Hong-Ru,Tian, Gao-Fei,Tian, Jun,Mao, Xiao-Li,Jia, Zheng-Hu,Meng, Zi-Yu,Zhao, Li-Qing,Yin, Zhi-Nan,Wu, Zhen-Zhou Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13

Tumors have evolved numerous mechanisms by which they can escape from immune surveillance. One of these is to produce immunosuppressive cytokines. Transforming growth factor-${\beta}$(TGF-${\beta}$) is a pleiotropic cytokine with a crucial function in mediating immune suppression, especially in the tumor microenvironment. TGF-${\beta}$ produced by T cells has been demonstrated as an important factor for suppressing antitumor immune responses, but the role of tumor-derived TGF-${\beta}$ in this process is poorly understood. In this study, we demonstrated that knockdown of tumor-derived TGF-${\beta}$ using shRNA resulted in dramatically reduced tumor size, slowing tumor formation, prolonging survival rate of tumor-bearing mice and inhibiting metastasis. We revealed possible underlying mechanisms as reducing the number of myeloid-derived suppressor cells (MDSC) and $CD4^+Foxp3^+$ Treg cells, and consequently enhanced IFN-${\gamma}$ production by CTLs. Knockdown of tumor-derived TGF-${\beta}$ also significantly reduced the conversion of na$\ddot{i}$ve $CD4^+$ T cells into Treg cells in vitro. Finally, we found that knockdown of TGF-${\beta}$ suppressed cell migration, but did not change the proliferation and apoptosis of tumor cells in vitro. In summary, our study provided evidence that tumor-derived TGF-${\beta}$ is a critical factor for tumor progression and evasion of immune surveillance, and blocking tumor-derived TGF-${\beta}$ may serve as a potential therapeutic approach for cancer.

Altered Biological Potential and Radioresponse of Murine Tumors in Different Microenvironments

이익재,이은정,박효진,김원우,하상준,신유근,성진실 대한암학회 2016 Cancer Research and Treatment Vol.48 No.2

Purpose This study was conducted to evaluate the biological features of murine hepatocarcinoma according to different tumor microenvironmental models and to determine the change in molecular and immunologic responses after radiation. Materials and Methods Tumor models were established in the liver (orthotopic) and thigh (heterotopic) of male C3H/HeN mice. Tumor growth and lung metastasis were assessed in these models. To evaluate the radiation effect, the tumors were irradiated with 10 Gy. Factors associated with tumor microenvironment including vascular endothelial growth factor (VEGF), cyclooxygenase- 2 (COX-2), transforming growth factor beta1 (TGF-!1), CD31, and serum interleukin- 6 (IL-6) were evaluated. Tumor-infiltrating regulatory immune cells, regulatory T cells (Tregs), and myeloid-derived suppressor cells (MDSCs) were also analyzed. Results A higher number of lung metastases were observed in the orthotopic tumor model than in the heterotopic tumor model. VEGF, CD31, COX-2, and TGF-!1 expression was more prominent in the orthotopic tumor model than in the heterotopic tumor model. Expression of the angiogenic factor VEGF and key regulatory molecules (TGF-!1 and COX-2) decreased following radiation in the orthotopic tumor model, while the serum IL-6 level increased after radiation. In the orthotopic tumor model, the number of both Tregs and MDSCs in the tumor burden decreased after radiation. Conclusion The orthotopic tumor model showed higher metastatic potential and more aggressive molecular features than the heterotopic tumor model. These findings suggest that the orthotopic tumor mouse model may be more reflective of the tumor microenvironment and suitable for use in the translational research of radiation treatment.

Inhibitory Effects of Dunning Rat Prostate Tumor Fluid on Proliferation of the Metastatic MAT-LyLu Cell Line

Bugan, Ilknur,Altun, Seyhan Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.2

Tumor fluid accumulation occurs in both human cancer and experimental tumor models. Solid tumors show a tendency to tumor fluid accumulation because of their anatomical and physiological features and this may be influenced by molecular factors. Fluid accumulation in the peri-tumor area also occurs in the Dunning model of rat prostate cancer as the tumor grows. In this study, the effects of tumor fluids that were obtained from Dunning prostate tumor-bearing Copenhagen rats on the strongly metastatic MAT-LyLu cell line were investigatedby examining the cell's migration and tumor fluid's toxicity and the kinetic parameters such as cell proliferation, mitotic index, and labelling index. In this research, tumor fluids were obtained from rats injected with $2{\times}10^5$ MAT-LyLu cells and treated with saline solution, and 200 nM tetrodotoxin (TTX), highly specific sodium channel blocker was used. Sterilized tumor fluids were added to medium of MAT-LyLu cells with the proportion of 20% in vitro. Consequently, it was demonstrated that Dunning rat prostate tumor fluid significantly inhibited proliferation (up to 50%), mitotic index, and labeling index of MAT-LyLu cells (up to 75%) (p<0.05) but stimulated the motility of the cells in vitro.

고관절주위 종양에 대한 임상적 고찰

김성준 ( Sung Joon Kim ),최일용 ( Il Yong Choi ),김태승 ( Tai Seung Kim ),안성철 ( Sung Chul Ahn ) 대한고관절학회 1991 Hip and Pelvis Vol.3 No.1

From January 1983 to December 1990, Sixty-six patients who have tumors around the hip joint and were confirmed their diagnosis by histopathological study have been reviewed and the following results were obtained. 1. There were forty-three cases(65.2%) of benign tumor and twenty-three(34.8%) malignant tumor. 2. Of the sixty-six patient, thirty-four were male and thirty-two female. In benign tumor, they shows relatively even distribution in age but in malignant tumors, thirteen cases(56.5%) were in the 5th and 6th decade. 3. Among the benign tumors, the soft tissue origin was nineteen cases and bony origin twenty-four. The most common tumor in soft tissue origin was lipoma (six cases(31.6%)) and bony origin unicameral bone cyst (nine cases(37.5%)). In malig- nent tumors. the metastatic carcinoma was most common (twelve cases(52.5%)) and the liver was most common primary site of cancer. 4. The most common chief complaint was mass (fourteen cases(32.6%)) in benign tumor and painful mass (eight(34.8%)) in malignant tumor. The duration of symptom ranged from 1 day to 33 years with an average of 3.6 years in benign tumor and from 2 weeks to 5 years (average 6 months) in malignant tumor. 5. Most of the benign tumors were treated by local excision, and malignant tumors were treated by wide excision, chemotherapy, radiation therapy, bipolar hemiarthroplasty, and tumor prosthesis or combination of them.

Homologous tumor cell membrane vesicles active preferential self‑recognition of tumor cells in vitro

Wu Chenghu,Yu Ailin,Chen Yue,Fan Mingbo 한국응용생명화학회 2022 Applied Biological Chemistry (Appl Biol Chem) Vol.65 No.1

Cell membrane vesicles, as delivery carriers of drugs or biological agents in vivo, are an important therapeutic mode in the study of disease treatment. Tumor membrane-derived vesicles have been widely used in tumor therapy because of their good tumor enrichment effect. The most common method is the surface of nanoparticles coated with tumor cell membrane, which can effectively prolong the circulation time of particles in the blood and the enrichment of tumors. In this study, we prepared vesicles of different tumor cell membrane derivate and studied their targeting to tumors detailly. The results showed that homologous vesicles have high targeting to homologous tumor cells. The fluorescence of vesicles in homologous tumor cells was significantly higher than that in other tumor cells. This study will provide a new strategy and guidance for the clinical treatment of cancer based on the tumor cell membrane system.