Cancer Research and Treatment

Original Articles

Genetic Profiles Associated with Chemoresistance in Patient-Derived Xenograft Models of Ovarian Cancer: Lan Ying Li, Hee Jung Kim, Sun Ae Park, So Hyun Lee, Lee Kyung Kim, Jung Yun Lee, Sunghoon Kim, Young Tae Kim, Sang Wun Kim, Eun Ji Nam; Cancer Res Treat. 2019;51(3):1117-1127. Published online November 6, 2018; DOI: https://doi.org/10.4143/crt.2018.405

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Purpose
Recurrence and chemoresistance (CR) are the leading causes of death in patients with high-grade serous carcinoma (HGSC) of the ovary. The aim of this study was to identify genetic changes associated with CR mechanisms using a patient-derived xenograft (PDX) mouse model and genetic sequencing.
Materials and Methods
To generate a CR HGSC PDX tumor, mice bearing subcutaneously implanted HGSC PDX tumors were treated with paclitaxel and carboplatin. We compared gene expression and mutations between chemosensitive (CS) and CR PDX tumors with whole exome and RNA sequencing and selected candidate genes. Correlations between candidate gene expression and clinicopathological variables were explored using the Cancer Genome Atlas (TCGA) database and the Human Protein Atlas (THPA).
Results
Three CR and four CS HGSC PDX tumor models were successfully established. RNA sequencing analysis of the PDX tumors revealed that 146 genes were significantly up-regulated and 54 genes down-regulated in the CR group compared with the CS group. Whole exome sequencing analysis showed 39 mutation sites were identified which only occurred in CR group. Differential expression of SAP25, HLA-DPA1, AKT3, and PIK3R5 genes and mutation of TMEM205 and POLR2A may have important functions in the progression of ovarian cancer chemoresistance. According to TCGA data analysis, patients with high HLA-DPA1 expression were more resistant to initial chemotherapy (p=0.030; odds ratio, 1.845).
Conclusion
We successfully established CR ovarian cancer PDX mouse models. PDX-based genetic profiling study could be used to select some candidate genes that could be targeted to overcome chemoresistance of ovarian cancer.

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Creation and Validation of Patient-Derived Cancer Model Using Peritoneal and Pleural Effusion in Patients with Advanced Ovarian Cancer: An Early Experience
Ruri Nishie, Tomohito Tanaka, Kensuke Hirosuna, Shunsuke Miyamoto, Hikaru Murakami, Hiromitsu Tsuchihashi, Akihiko Toji, Shoko Ueda, Natsuko Morita, Sousuke Hashida, Atsushi Daimon, Shinichi Terada, Hiroshi Maruoka, Hiromi Konishi, Yuhei Kogata, Kohei Tan
Journal of Clinical Medicine.2024; 13(9): 2718. CrossRef
Uncovering miRNA–mRNA Regulatory Networks Related to Olaparib Resistance and Resensitization of BRCA2MUT Ovarian Cancer PEO1-OR Cells with the ATR/CHK1 Pathway Inhibitors
Łukasz Biegała, Damian Kołat, Arkadiusz Gajek, Elżbieta Płuciennik, Agnieszka Marczak, Agnieszka Śliwińska, Michał Mikula, Aneta Rogalska
Cells.2024; 13(10): 867. CrossRef
Patient-derived xenograft models in cancer therapy: technologies and applications
Yihan Liu, Wantao Wu, Changjing Cai, Hao Zhang, Hong Shen, Ying Han
Signal Transduction and Targeted Therapy.2023;[Epub] CrossRef
Deregulations of RNA Pol II Subunits in Cancer
Martina Muste Sadurni, Marco Saponaro
Applied Biosciences.2023; 2(3): 459. CrossRef
Transcriptome and Metabolome Analyses Reveal the Mechanism of Corpus Luteum Cyst Formation in Pigs
Jiage Dai, Jiabao Cai, Taipeng Zhang, Mingyue Pang, Xiaoling Xu, Jiahua Bai, Yan Liu, Yusheng Qin
Genes.2023; 14(10): 1848. CrossRef
Prediction of Chemoresistance—How Preclinical Data Could Help to Modify Therapeutic Strategy in High-Grade Serous Ovarian Cancer
Jacek Wilczyński, Edyta Paradowska, Justyna Wilczyńska, Miłosz Wilczyński
Current Oncology.2023; 31(1): 229. CrossRef
Personalization of Therapy in High-Grade Serous Tubo-Ovarian Cancer—The Possibility or the Necessity?
Jacek Wilczyński, Edyta Paradowska, Miłosz Wilczyński
Journal of Personalized Medicine.2023; 14(1): 49. CrossRef
PIK3R5 genetic predictors of hypertension induced by VEGF-pathway inhibitors
Julia C. F. Quintanilha, Alessandro Racioppi, Jin Wang, Amy S. Etheridge, Stefanie Denning, Carol E. Peña, Andrew D. Skol, Daniel J. Crona, Danyu Lin, Federico Innocenti
The Pharmacogenomics Journal.2022; 22(1): 82. CrossRef
AKT Isoforms Interplay in High-Grade Serous Ovarian Cancer Prognosis and Characterization
Eros Azzalini, Domenico Tierno, Michele Bartoletti, Renzo Barbazza, Giorgio Giorda, Fabio Puglisi, Sabrina Chiara Cecere, Nunzia Simona Losito, Daniela Russo, Giorgio Stanta, Vincenzo Canzonieri, Serena Bonin
Cancers.2022; 14(2): 304. CrossRef
Comparative analysis of cancer gene mutations using targeted sequencing in matched primary and recurrent gastric cancers after chemotherapy
Yeon-Ju Huh, Sung-Yup Cho, Min-Sun Cho, Kyoung-Eun Lee, Joo-Ho Lee
Genes & Genomics.2022; 44(11): 1425. CrossRef
Validation of a Patient-Derived Xenograft Model for Cervical Cancer Based on Genomic and Phenotypic Characterization
Shunsuke Miyamoto, Tomohito Tanaka, Kensuke Hirosuna, Ruri Nishie, Shoko Ueda, Sousuke Hashida, Shinichi Terada, Hiromi Konishi, Yuhei Kogata, Kohei Taniguchi, Kazumasa Komura, Masahide Ohmichi
Cancers.2022; 14(12): 2969. CrossRef
HCP5, as the sponge of miR-1291, facilitates AML cell proliferation and restrains apoptosis via increasing PIK3R5 expression
Yan Liu, Xue-Bing Jing, Zhen-Cheng Wang, Qing-Kun Han
Human Genomics.2021;[Epub] CrossRef
Leveraging Genomics, Transcriptomics, and Epigenomics to Understand the Biology and Chemoresistance of Ovarian Cancer
Sandra Muñoz-Galván, Amancio Carnero
Cancers.2021; 13(16): 4029. CrossRef
CD83, a Novel MAPK Signaling Pathway Interactor, Determines Ovarian Cancer Cell Fate
Aalia Batool, Hao Liu, Yi-Xun Liu, Su-Ren Chen
Cancers.2020; 12(8): 2269. CrossRef
A recombinant platform to characterize the role of transmembrane protein hTMEM205 in Pt(ii)-drug resistance and extrusion
Marc J Gallenito, Tahir S Qasim, Jasmine N Tutol, Ved Prakash, Sheel C Dodani, Gabriele Meloni
Metallomics.2020; 12(10): 1542. CrossRef
Function, Regulation and Biological Roles of PI3Kγ Variants
Bernd Nürnberg, Sandra Beer-Hammer
Biomolecules.2019; 9(9): 427. CrossRef

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Comparison of Clinical Features and Outcomes in Epithelial Ovarian Cancer according to Tumorigenicity in Patient-Derived Xenograft Models: Kyung Jin Eoh, Young Shin Chung, So Hyun Lee, Sun-Ae Park, Hee Jung Kim, Wookyeom Yang, In Ok Lee, Jung-Yun Lee, Hanbyoul Cho, Doo Byung Chay, Sunghoon Kim, Sang Wun Kim, Jae-Hoon Kim, Young Tae Kim, Eun Ji Nam; Cancer Res Treat. 2018;50(3):956-963. Published online October 17, 2017; DOI: https://doi.org/10.4143/crt.2017.181

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Purpose
Although the use of xenograft models is increasing, few studies have compared the clinical features or outcomes of epithelial ovarian cancer (EOC) patients according to the tumorigenicity of engrafted specimens. The purpose of this study was to evaluate whether tumorigenicity was associated with the clinical features and outcomes of EOC patients.
Materials and Methods
Eighty-eight EOC patients who underwent primary or interval debulking surgery from June 2014 to December 2015 were included. Fresh tumor specimens were implanted subcutaneously on each flank of immunodeficient mice. Patient characteristics, progression-free survival (PFS), and germline mutation spectra were compared according to tumorigenicity.
Results
Xenografts were established successfully from 49 of 88 specimens. Tumorigenicity was associated with lymphovascular invasion and there was a propensity to engraft successfully with high-grade tumors. Tumors from patientswho underwent non-optimal (residual disease ≥ 1 cm) primary orinterval debulking surgery had a significantly greater propensity to achieve tumorigenicity than those who received optimal surgery. In addition, patients whose tumors became engrafted seemed to have a shorter PFS and more frequent germline mutations than patients whose tumors failed to engraft. Tumorigenicity was a significant factor for predicting PFS with advanced International Federation of Gynecology and Obstetrics stage and high-grade cancers.
Conclusions
Tumorigenicity in a xenograft model was a strong prognostic factor and was associated with more aggressive tumors in EOC patients. Xenograft models can be useful as a preclinical tool to predict prognosis and could be applied to further pharmacologic and genomic studies on personalized treatments.

Citations

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TOWARDS Study: Patient-Derived Xenograft Engraftment Predicts Poor Survival in Patients With Newly Diagnosed Triple-Negative Breast Cancer
Christos Vaklavas, Cindy B. Matsen, Zhengtao Chu, Kenneth M. Boucher, Sandra D. Scherer, Satya Pathi, Anna Beck, Kirstyn E. Brownson, Saundra S. Buys, Namita Chittoria, Elyse D'Astous, H. Evin Gulbahce, N. Lynn Henry, Stephen Kimani, Jane Porretta, Regina
JCO Precision Oncology.2024;[Epub] CrossRef
Generation, evolution, interfering factors, applications, and challenges of patient-derived xenograft models in immunodeficient mice
Mingtang Zeng, Zijing Ruan, Jiaxi Tang, Maozhu Liu, Chengji Hu, Ping Fan, Xinhua Dai
Cancer Cell International.2023;[Epub] CrossRef
Cancer “Avatars”: Patient-Derived Xenograft Growth Correlation with Postoperative Recurrence and Survival in Pancreaticobiliary Cancer
Isaac T Lynch, Amro M Abdelrahman, Roberto Alva-Ruiz, Alessandro Fogliati, Rondell P Graham, Rory Smoot, Mark J Truty
Journal of the American College of Surgeons.2023; 237(3): 483. CrossRef
Identification of Prognostic Markers of Gynecologic Cancers Utilizing Patient-Derived Xenograft Mouse Models
Ha-Yeon Shin, Eun-ju Lee, Wookyeom Yang, Hyo Sun Kim, Dawn Chung, Hanbyoul Cho, Jae-Hoon Kim
Cancers.2022; 14(3): 829. CrossRef
Experimental models for ovarian cancer research
Sum In Tsang, Ayon A. Hassan, Sally K.Y. To, Alice S.T. Wong
Experimental Cell Research.2022; 416(1): 113150. CrossRef
Preclinical models of epithelial ovarian cancer: practical considerations and challenges for a meaningful application
Alessandra Ciucci, Marianna Buttarelli, Anna Fagotti, Giovanni Scambia, Daniela Gallo
Cellular and Molecular Life Sciences.2022;[Epub] CrossRef
Harnessing preclinical models for the interrogation of ovarian cancer
Tianyu Qin, Junpeng Fan, Funian Lu, Li Zhang, Chen Liu, Qiyue Xiong, Yang Zhao, Gang Chen, Chaoyang Sun
Journal of Experimental & Clinical Cancer Research.2022;[Epub] CrossRef
Prognostic value of patient‐derived xenograft engraftment in pediatric sarcomas
Helena Castillo‐Ecija, Guillem Pascual‐Pasto, Sara Perez‐Jaume, Claudia Resa‐Pares, Monica Vila‐Ubach, Carles Monterrubio, Ana Jimenez‐Cabaco, Merce Baulenas‐Farres, Oscar Muñoz‐Aznar, Noelia Salvador, Maria Cuadrado‐Vilanova, Nagore G Olaciregui, Leire B
The Journal of Pathology: Clinical Research.2021; 7(4): 338. CrossRef
Patient-Derived Xenograft Models in Cervical Cancer: A Systematic Review
Tomohito Tanaka, Ruri Nishie, Shoko Ueda, Shunsuke Miyamoto, Sousuke Hashida, Hiromi Konishi, Shinichi Terada, Yuhei Kogata, Hiroshi Sasaki, Satoshi Tsunetoh, Kohei Taniguchi, Kazumasa Komura, Masahide Ohmichi
International Journal of Molecular Sciences.2021; 22(17): 9369. CrossRef
Biliary tract cancer patient-derived xenografts: Surgeon impact on individualized medicine
Jennifer L. Leiting, Stephen J. Murphy, John R. Bergquist, Matthew C. Hernandez, Tommy Ivanics, Amro M. Abdelrahman, Lin Yang, Isaac Lynch, James B. Smadbeck, Sean P. Cleary, David M. Nagorney, Michael S. Torbenson, Rondell P. Graham, Lewis R. Roberts, Gr
JHEP Reports.2020; 2(2): 100068. CrossRef
Patient-derived xenograft model engraftment predicts poor prognosis after surgery in patients with pancreatic cancer
Qi Chen, Tao Wei, Jianxin Wang, Qi Zhang, Jin Li, Jingying Zhang, Lei Ni, Yi Wang, Xueli Bai, Tingbo Liang
Pancreatology.2020; 20(3): 485. CrossRef
A Biobank of Colorectal Cancer Patient-Derived Xenografts
Suad M. Abdirahman, Michael Christie, Adele Preaudet, Marie C. U. Burstroem, Dmitri Mouradov, Belinda Lee, Oliver M. Sieber, Tracy L. Putoczki
Cancers.2020; 12(9): 2340. CrossRef
High-Grade Serous Ovarian Cancer: Basic Sciences, Clinical and Therapeutic Standpoints
Michael-Antony Lisio, Lili Fu, Alicia Goyeneche, Zu-hua Gao, Carlos Telleria
International Journal of Molecular Sciences.2019; 20(4): 952. CrossRef
Efficient use of patient-derived organoids as a preclinical model for gynecologic tumors
Yoshiaki Maru, Naotake Tanaka, Makiko Itami, Yoshitaka Hippo
Gynecologic Oncology.2019; 154(1): 189. CrossRef
Current Status of Patient-Derived Ovarian Cancer Models
Yoshiaki Maru, Yoshitaka Hippo
Cells.2019; 8(5): 505. CrossRef
Establishment of patient‐derived xenograft model in ovarian cancer and its influence factors analysis
Jianfa Wu, Yunxi Zheng, Qi Tian, Ming Yao, Xiaofang Yi
Journal of Obstetrics and Gynaecology Research.2019; 45(10): 2062. CrossRef
Ovarian Cancers: Genetic Abnormalities, Tumor Heterogeneity and Progression, Clonal Evolution and Cancer Stem Cells
Ugo Testa, Eleonora Petrucci, Luca Pasquini, Germana Castelli, Elvira Pelosi
Medicines.2018; 5(1): 16. CrossRef

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Long Non-coding RNA HOXA11 Antisense Promotes Cell Proliferation and Invasion and Predicts Patient Prognosis in Serous Ovarian Cancer: Ga Won Yim, Hee Jung Kim, Lee Kyung Kim, Sang Wun Kim, Sunghoon Kim, Eun Ji Nam, Young Tae Kim; Cancer Res Treat. 2017;49(3):656-668. Published online October 11, 2016; DOI: https://doi.org/10.4143/crt.2016.263

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Purpose
The biological function of long non-coding RNAs (lncRNAs) is only partially understood; therefore, in this study, we investigated the expression of the novel HOXA11 antisense (HOXA11as) lncRNA and its oncogenic role in serous ovarian cancer (SOC).
Materials and Methods
HOXA11as expression was examined in 129 SOC tissue samples by real time reverse transcription polymerase chain reaction. Clinicopathological factors and patient survival were compared between the high (n=27) and low HOXA11as expression group (n=102). To investigate the role of HOXA11as in cell proliferation, invasion, and migration, HOXA11as expression in ovarian cancer cells was knocked down using RNA interference.
Results
HOXA11as expression in cancer tissue was 77-fold higher than that of noncancerous tissue (p < 0.05). Higher HOXA11as expression was significantly correlated with histological grade (p=0.017) and preoperative cancer antigen 125 (p=0.048). HOXA11as overexpression in SOC cells led to increased cell proliferation, invasion, and migration. Moreover, HOXA11as was associated with the expression of genes involved in cell invasion, migration, and epithelial-mesenchymal transition (EMT), including vascular endothelial growth factor, matrix metalloproteinase 9 (MMP-9), B-catenin, E-cadherin, Snail, Twist, and vimentin. Multivariate analysis revealed that HOXA11as was a prognostic factor of progressive disease and mortality (hazard ratio [HR], 1.730; p=0.043 and HR, 2.170; p=0.033, respectively). Progression-free and overall survival were significantly shorter in patients with high HOXA11as expression.
Conclusion
These findings highlight the clinical significance of HOXA11as to predicting the prognosis of SOC patients and suggest its potential in promoting tumor aggressiveness via regulation of vascular endothelial growth factor (VEGF), MMP-9, and EMT-related mechanisms.

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The Role of EMT-Related lncRNAs in Ovarian Cancer
Dimitra Ioanna Lampropoulou, Marios Papadimitriou, Christos Papadimitriou, Dimitrios Filippou, Georgia Kourlaba, Gerasimos Aravantinos, Maria Gazouli
International Journal of Molecular Sciences.2023; 24(12): 10079. CrossRef
LncRNAs and the Angiogenic Switch in Cancer: Clinical Significance and Therapeutic Opportunities
Peace Mabeta, Rodney Hull, Zodwa Dlamini
Genes.2022; 13(1): 152. CrossRef
Long non-coding RNA HOXA11-AS knockout inhibits proliferation and overcomes drug resistance in ovarian cancer
Yuwei Chen, Zhaolei Cui, Qiaoling Wu, Huihui Wang, Hongmei Xia, Yang Sun
Bioengineered.2022; 13(5): 13893. CrossRef
The role of altered long noncoding RNAs in overall survival of ovarian cancer: A systematic review and meta-analysis
Elahe Seyed Hosseini, Marziyeh Alizadeh Zarei, Hamed Haddad Kashani, Alireza Milajerdi, Zahra Zare Dehghanani, Hassan Hassani Bafrani, Hossein Nikzad
Pathology - Research and Practice.2021; 219: 153363. CrossRef
Non-Coding RNAs as Biomarkers of Tumor Progression and Metastatic Spread in Epithelial Ovarian Cancer
Karolina Seborova, Radka Vaclavikova, Lukas Rob, Pavel Soucek, Pavel Vodicka
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Alexey V. Zamaraev, Pavel I. Volik, Gennady T. Sukhikh, Gelina S. Kopeina, Boris Zhivotovsky
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Panminerva Medica.2021;[Epub] CrossRef
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Soudeh Ghafouri-Fard, Mohammadhosein Esmaeili, Hamed Shoorei, Mohammad Taheri
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Lin Deng, Ding-qing Feng, Bin Ling
Journal of Zhejiang University-SCIENCE B.2020; 21(4): 315. CrossRef
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Sun-Ae Park, Lee Kyung Kim, Young Tae Kim, Tae-Hwe Heo, Hee Jung Kim
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Jianing Xu, Qiyu Bo, Xiang Zhang, Dapeng Lei, Jue Wang, Xinliang Pan
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Jin-yan Wang, Ai-qing Lu, Li-juan Chen
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Chu Zhang, Jie Liu, Yang Zhang, Chengyan Luo, Tong Zhu, Rongrong Zhang, Ruiqin Yao
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Lei Zhan, Jun Li, Bing Wei
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Cheng‐Wei Lu, Dan‐Dan Zhou, Tian Xie, Ji‐Long Hao, Om Prakash Pant, Cheng‐Bo Lu, Xiu‐Fen Liu
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Puxiang Chen, Xiaolin Fang, Bing Xia, Yan Zhao, Qiaoyan Li, Xiaoying Wu
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RETRACTED ARTICLE: Systematic analyses reveal long non-coding RNA (PTAF)-mediated promotion of EMT and invasion-metastasis in serous ovarian cancer
Haihai Liang, Xiaoguang Zhao, Chengyu Wang, Jian Sun, Yingzhun Chen, Guoyuan Wang, Lei Fang, Rui Yang, Mengxue Yu, Yunyan Gu, Hongli Shan
Molecular Cancer.2018;[Epub] CrossRef
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Mei S Ong, Wanpei Cai, Yi Yuan, Hin C Leong, Tuan Z Tan, Asad Mohammad, Ming L You, Frank Arfuso, Boon C Goh, Sudha Warrier, Gautam Sethi, Nicholas S Tolwinski, Peter E Lobie, Celestial T Yap, Shing C Hooi, Ruby Y Huang, Alan P Kumar
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Synergistic Effect of COX-2 Inhibitor on Paclitaxel-Induced Apoptosis in the Human Ovarian Cancer Cell Line OVCAR-3: Hee Jung Kim, Ga Won Yim, Eun Ji Nam, Young Tae Kim; Cancer Res Treat. 2014;46(1):81-92. Published online January 15, 2014; DOI: https://doi.org/10.4143/crt.2014.46.1.81

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PURPOSE
Celecoxib, a highly selective cyclooxygenase-2 inhibitor, regulates apoptosis of several types of human cancer cells. The purpose of this study was to investigate whether celecoxib in combination with paclitaxel modulates apoptosis of ovarian cancer cells, and to identify the signal pathway by which celecoxib mediates apoptosis.
MATERIALS AND METHODS
OVCAR-3 cells were exposed to paclitaxel (20 microM) in the absence or presence of celecoxib (10 microM). Cell viability was evaluated using a Cell Counting Kit-8 assay. Apoptosis was evaluated using Annexin-V/7-aminoactinomycin D staining and a cellular DNA fragmentation enzyme-linked immunosorbent assay. Caspase-3, -9, and cleavage of poly ADP-ribose polymerase (PARP) were determined by western blotting. Expression of nuclear factor-kappaB (NF-kappaB) and vascular endothelial growth factor (VEGF) and Akt activation were assessed using reverse transcriptase-polymerase chain reaction and western blotting.
RESULTS
Celecoxib enhanced paclitaxel-induced growth inhibition of OVCAR-3 cells. Celecoxib significantly increased paclitaxel-induced apoptosis of OVCAR-3 cells. Pretreatment with celecoxib also increased activation of caspase-9, -3 and cleaved PARP following paclitaxel-treatment. Exposure of OVCAR-3 cells to celecoxib in combination with paclitaxel resulted in downregulation of NF-kappaB activation and VEGF expression. Furthermore, combining celecoxib and paclitaxel inhibited phosphorylation of Akt.
CONCLUSION
OVCAR-3 cells were sensitized to paclitaxel-induced apoptosis by celecoxib through downregulation of NF-kappaB and Akt activation, suggesting that celecoxib may work synergistically with paclitaxel to inhibit different targets and ultimately produce anticancer effects. Combining celecoxib with paclitaxel may prove beneficial in the clinical treatment of ovarian cancer.

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Cyclooxygenase-2 promotes ovarian cancer cell migration and cisplatin resistance via regulating epithelial mesenchymal transition
Lin Deng, Ding-qing Feng, Bin Ling
Journal of Zhejiang University-SCIENCE B.2020; 21(4): 315. CrossRef
Paclitaxel induces apoptosis through the TAK1–JNK activation pathway
Di Yu‐Wei, Zhuo‐sheng Li, Shu‐min Xiong, Ge Huang, Yan‐fei Luo, Tie‐ying Huo, Mao‐hua Zhou, You‐wei Zheng
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A Case of Cryptococcal Meningitis in a Brest Cancer Patient with Liver Metastasis, Suffering from Herpes Zoster: Chul Woo Ahn, Wook Jin Chung, Beom Seok Kim, Se Hang Cho, Sun Young Rha, Hyun Cheol Chung, Joo Hang Kim, Jae Kyung Roh, Byung Soo Kim, Hee Jung Kim, Kwang Gil Lee; J Korean Cancer Assoc. 1997;29(3):540-540.

Abstract PDF: Cryptococcosis is a relatively common mycosis of human caused by a worldwide Cryptococcus neoformans. Cryptococcosis occurs more frequently in immuno-compromised hosts such as patients with lymphoma, AIDS, leukemia and other debilitating diseases which manifest a condition of altered cell mediated immunity. Also cancer patients with anticancer chemotherapy are at high risk. Cryptococcosis is primarily a pulmonary disease that remains asymptomatic and unrecognised in most cases. Meningitic and meningoencephalitc forms are more frequently diagnosed because of their striking clinical symptoms.Meningoencephalitis is an uncommon form of cryptoccocosis that often leads to coma and death within a short time, if it is not quickly diagnosed and treated properly. The treatment of choice for the cryptococcosis consists of intravenous amphotericin B and 5-fluorocytocine. We report a case of cryptococcal meningitis in 47-year-old female breast cancer patient with liver metastasis after systemic chemotherapy. She complained headach, fever and diagnosed as cryptococcal meningitis after the India ink smear and culture of CSF. After treated with amphotericin B, her conditions were improved.

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