Cancer Research and Treatment

Volume 45(2); June 2013

Review Article

Treatment of Non-small Cell Lung Carcinoma after Failure of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor: Jae Cheol Lee, Seung Hun Jang, Kye Young Lee, Young-Chul Kim; Cancer Res Treat. 2013;45(2):79-85. Published online June 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.2.79

Since the first description of non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutation as a distinct clinical entity, studies have proved EGFR tyrosine kinase inhibitors (TKIs) as a first choice of treatment. The median response duration of TKIs as a first-line treatment for EGFR mutant tumors ranges from 11 to 14 months. However, acquired resistance to EGFR-TKIs is inevitable due to various mechanisms, such as T790M, c-Met amplification, activation of alternative pathways (IGF-1, HGF, PI3CA, AXL), transformation to mesenchymal cell or small cell features, and tumor heterogeneity. Until development of a successful treatment strategy to overcome such acquired resistance, few options are currently available. Here we provide a summary of the therapeutic options after failure of first line EGFR-TKI treatment for NSCLC.

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Original Articles

Trends in Cancer Screening Rates among Korean Men and Women: Results from the Korean National Cancer Screening Survey, 2004-2012: Mina Suh, Kui Son Choi, Yoon Young Lee, Jae Kwan Jun; Cancer Res Treat. 2013;45(2):86-94. Published online June 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.2.86

Abstract PDF PubReader ePub

PURPOSE
The Korean National Cancer Screening Survey (KNCSS), a nationwide, annual cross-sectional survey, has been conducted since 2004. The current study was conducted in order to report on trends in cancer screening rates for five types of cancer (stomach, liver, colorectal, breast, and cervix uteri).
MATERIALS AND METHODS
KNCSS data were collected between 2004 and 2012. The eligible study population included cancer-free men who were 40 years of age and older and women who were 30 years of age and older. The lifetime screening rate, screening rate with recommendation, and changes in annual rates were calculated.
RESULTS
Lifetime screening rates and screening rates with recommendation for the five types of cancer rose steadily until 2010, showed a slight drop or were stable in 2011, and increased again in 2012. On average, screening rates with recommendation have shown annual increases of 4.3% (95% confidence interval [CI], 3.6 to 5.0%) for stomach cancer, 0.8% (95% CI, -0.5 to 2.1%) for liver cancer, 2.4% (95% CI, 1.3 to 3.5%) for colorectal cancer, 4.5% (95% CI, 3.9 to 5.1%) for breast cancer, and 1.3% (95% CI, 0.6 to 2.0%) for cervical cancer. Disparities in age groups and household incomes have been decreasing since 2004.
CONCLUSION
Cancer screening rates in Korea showed a significant increase from 2004 to 2012, and screening rates for gastric and breast cancer are now approaching 70%. The 10-Year Plan for Cancer Control target for screening rates was met or nearly met for all cancer types examined, with the exception of liver and colorectal cancer.

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Predicting Survival in Patients with Advanced Non-squamous Non-small Cell Lung Cancer: Validating the Extent of Metastasis: Dong Soo Lee, Jin Hyoung Kang, Chang Geol Lee, Seoung Jun Kim, Young Jin Choi, Kyo Young Lee, Yeon Sil Kim; Cancer Res Treat. 2013;45(2):95-102. Published online June 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.2.95

Abstract PDF PubReader ePub

PURPOSE
A number of factors related to overall survival (OS) have been addressed in advanced non-small cell lung cancer (NSCLC). This study was conducted to determine the impact of whole-body metastatic regions on survival outcome in advanced non-squamous NSCLC.
MATERIALS AND METHODS
Between March 2005 and February 2011, 112 eligible patients with newly confirmed stage IV non-squamous NSCLC, available for epidermal growth factor receptor (EGFR) mutation status 18-21 analysis, and accessible for the determination of pretreatment whole-body metastatic regions were enrolled in this retrospective study. The total number of synchronous metastatic regions was scored according to the following disease sites: abdomen/pelvis, lung to lung/pulmonary lymphangitic spread, bone, pleura/pleural effusion/pericardial effusion, neck/axillary lymph nodes, other soft tissue, brain.
RESULTS
The median age of the cohort was 65 years (range, 31 to 88 years). The median whole-body metastatic score was 2 (range, 1 to 6), and bone and lung to lung were the most common metastatic sites. EGFR mutations were observed in 40 (35.7%) patients with a deletion in exon 19 and Leu858Arg mutation in exon 21 being detected in 16 (40.0%) and 19 (47.5%) patients, respectively. Multivariate analysis for OS revealed that treatment factors (p=0.005), performance status (p=0.006), whole-body metastatic score (p<0.001), and EGFR mutation status (p=0.095) were significantly or marginally associated with OS.
CONCLUSION
The results of the present study demonstrated that whole-body metastatic extent strongly affects survival outcome, even after adjustment for other significant variables in advanced non-squamous NSCLC. The clinical validity of more curative multimodal approaches in cohorts with limited metastases remains to be explored.

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JIACHENG SONG, JING YU, ZHANLONG MA, SHANSHAN LU
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Is second-line systemic chemotherapy beneficial in patients with non-small cell lung cancer (NSCLC)? A multicenter data evaluation by the Anatolian Society of Medical Oncology
Hatice Odabas, Arife Ulas, Kubra Aydin, Mevlude Inanc, Asude Aksoy, Dogan Yazilitas, Mehmet Turkeli, Sinemis Yuksel, Ali Inal, Ahmet S. Ekinci, Alper Sevinc, Nebi S. Demirci, Mukremin Uysal, Necati Alkis, Faysal Dane, Mehmet Aliustaoglu, Mahmut Gumus
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Clinical Correlation Between Tumor Maximal Standardized Uptake Value in Metabolic Imaging and Metastatic Tumor Characteristics in Advanced Non-small Cell Lung Cancer
Dong Soo Lee, Seung Joon Kim, Hong Seok Jang, Ie Ryung Yoo, Kyung Ran Park, Sae Jung Na, Kyo Young Lee, Sook Hee Hong, Jin Hyoung Kang, Young Kyoon Kim, Yeon Sil Kim
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A case of lung cancer complicated by axillary Castleman's disease
Manabu Kakizoe, Kousuke Suzuki, Noriyuki Saeki
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Non-small cell lung cancer metastasis to the oral cavity: a case report
JB Olsen, F Sim, A Chandu
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Lung Cancer Coexisting With Ipsilateral Pleural Effusion
Francisco Rodriguez-Panadero, Beatriz Romero-Romero
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EGFR endocytosis is a novel therapeutic target in lung cancer with wild-type EGFR
Ukhyun Jo, Kyong Hwa Park, Young Mi Whang, Jae Sook Sung, Nam Hee Won, Jong Kuk Park, Yeul Hong Kim
Oncotarget.2014; 5(5): 1265. CrossRef

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Which Patients Might Benefit from Postmastectomy Radiotherapy in Breast Cancer Patients with T1-2 Tumor and 1-3 Axillary Lymph Nodes Metastasis?: Moonkyoo Kong, Seong Eon Hong; Cancer Res Treat. 2013;45(2):103-111. Published online June 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.2.103

Abstract PDF PubReader ePub

PURPOSE
This study compared the clinical outcomes of T1-2N1 breast cancer patients with and without postmastectomy radiotherapy (PMRT). Risk factors for loco-regional recurrence (LRR) were identified in order to define a subgroup of patients who might benefit from PMRT.
MATERIALS AND METHODS
Of 110 T1-2N1 breast cancer patients who underwent mastectomy from January 1994 through December 2009, 32 patients underwent PMRT and 78 patients did not. Treatment outcomes and risk factors for LRR were analyzed.
RESULTS
The 5- and 10-year LRR rates were both 6.2% in the PMRT group, and 10.4% and 14.6% in the no-PMRT group (p=0.336). In addition, no significant differences in distant metastasis-free survival (DMFS) or overall survival (OS) were observed between patients receiving and not receiving PMRT. In multivariate analysis, factors associated with higher LRR rates included grade 3 disease, extracapsular extension (ECE), and triple negative subtype. Patients who had one or more risk factors for LRR were defined as a high-risk patient group. In the high-risk group, both 5- and 10-year LRR rates for patients who underwent PMRT was 18.2%, and LRR rates of 21.4% at five years and 36.6% at 10 years were observed for patients who did not undergo PMRT (p=0.069).
CONCLUSION
PMRT in T1-2N1 breast cancer patients should be considered according to several prognostic factors in addition to T and N stage. Findings of our study indicated that PMRT did not improve LRR, DMFS, or OS in T1-2N1 breast cancer patients. However, in a subgroup of patients with grade 3 disease, ECE, or triple negative subtype, PMRT might be beneficial.

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A Prognostic Risk Stratification Model to Identify Potential Population Benefiting From Postmastectomy Radiotherapy in T1–2 Breast Cancer With 1–3 Positive Axillary Lymph Nodes
Niuniu Hou, Juliang Zhang, Lu Yang, Ying Wu, Zhe Wang, Mingkun Zhang, Li Yang, Guangdong Hou, Jianfeng Wu, Yidi Wang, Bingyao Dong, Lili Guo, Mei Shi, Rui Ling
Frontiers in Oncology.2021;[Epub] CrossRef
SKIN AND SUBCUTANEOUS ADIPOSE TISSUE DAMAGE AFTER RADIATION THERAPY IN BREAST CANCER PATIENTS
D. Bazyka, O. Litvinenko, S. Bugaytsov, G. Shakhrai
Проблеми радіаційної медицини та радіобіології = Problems of Radiation Medicine and Radiobiology.2021; 26: 18. CrossRef
Multidisciplinary Management of the Axilla in Patients with cT1-T2 N0 Breast Cancer Undergoing Primary Mastectomy: Results from a Prospective Single-Institution Series
Samantha Grossmith, Anvy Nguyen, Jiani Hu, Jennifer K. Plichta, Faina Nakhlis, Linda Cutone, Laura Dominici, Mehra Golshan, Margaret Duggan, Katharine Carter, Esther Rhei, Thanh Barbie, Katherina Calvillo, Suniti Nimbkar, Jennifer Bellon, Julia Wong, Rina
Annals of Surgical Oncology.2018; 25(12): 3527. CrossRef
A prognostic score model to determine which breast cancer patients with 1-3 positive lymph nodes after modified radical mastectomy should receive radiotherapy
Dawei Chen, Haiyong Wang, Xinyu Song, Fang Shi, Li Kong, Jinming Yu
Oncotarget.2018; 9(1): 385. CrossRef
Postmastectomy radiation therapy for breast cancer patients with one to three positive lymph nodes: a propensity score matching analysis
Jiamao Lin, Cheng Li, Chenyue Zhang, Fang Shi, Haiyong Wang
Future Oncology.2017; 13(16): 1395. CrossRef
Predicting loco-regional recurrence risk in T1, T2 breast cancer with 1–3 positive axillary nodes postmastectomy: Development of a predictive nomogram
T Wadasadawala, S Kannan, S Gudi, A Rishi, A Budrukkar, V Parmar, T Shet, S Desai, S Gupta, R Badwe, R Sarin
Indian Journal of Cancer.2017; 54(1): 352. CrossRef
Comparison of Treatment Outcomes between Breast Conserving Surgery Followed by Radiotherapy and Mastectomy Alone in Patients with T1-2 Stage and 1-3 Axillary Lymph Nodes in the Era of Modern Adjuvant Systemic Treatments
Sang-Won Kim, Mison Chun, Sehwan Han, Yong Sik Jung, Jin Hyuk Choi, Seok Yun Kang, Hyunsoo Jang, Sunmi Jo, William B. Coleman
PLOS ONE.2016; 11(9): e0163748. CrossRef
Improvement of survival with postmastectomy radiotherapy in patients with 1-3 positive axillary lymph nodes: A systematic review and meta-analysis of the current literature
Hannah Headon, Abdul Kasem, Reham Almukbel, Kefah Mokbel
Molecular and Clinical Oncology.2016; 5(4): 429. CrossRef
ABCB1 polymorphism as prognostic factor in breast cancer patients treated with docetaxel and doxorubicin neoadjuvant chemotherapy
Hee‐Jun Kim, Seock‐Ah Im, Bhumsuk Keam, Hye Seon Ham, Kyung Hun Lee, Tae Yong Kim, Yu Jung Kim, Do‐Youn Oh, Jee Hyun Kim, Wonshik Han, In‐Jin Jang, Tae‐You Kim, In Ae Park, Dong Young Noh
Cancer Science.2015; 106(1): 86. CrossRef
Conservative Axillary Surgery in Breast Cancer Patients Undergoing Mastectomy: Long-Term Results
Michael S. Cowher, Stephen R. Grobmyer, Joanne Lyons, Colin O'Rourke, Deborah Baynes, Joseph P. Crowe
Journal of the American College of Surgeons.2014; 218(4): 819. CrossRef

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Clinical Outcome of Rituximab-Based Therapy (RCHOP) in Diffuse Large B-Cell Lymphoma Patients with Bone Marrow Involvement: Byung Woog Kang, Joon Ho Moon, Yee Soo Chae, Soo Jung Lee, Jong Gwang Kim, Yeo-Kyeoung Kim, Je-Jung Lee, Deok-Hwan Yang, Hyeoung-Joon Kim, Jin Young Kim, Young Rok Do, Keon Uk Park, Hong Suk Song, Ki Young Kwon, Min Kyung Kim, Kyung Hee Lee, Myung Soo Hyun, Hun Mo Ryoo, Sung Hwa Bae, Hwak Kim, Sang Kyun Sohn; Cancer Res Treat. 2013;45(2):112-117. Published online June 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.2.112

Abstract PDF PubReader ePub

PURPOSE
We investigated the clinical outcome of bone marrow (BM) involvement in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy.
MATERIALS AND METHODS
A total of 567 consecutive patients with newly diagnosed DLBCL treated with rituximab-CHOP (RCHOP) between November 2001 and March 2010 were included in the current study. All of the patients underwent a BM study at the initial staging and the clinical characteristics and prognosis of these patients with or without BM involvement were analyzed retrospectively.
RESULTS
The total cohort included 567 patients. The overall incidence of BM involvement was 8.5%. With a median follow-up duration of 33.2 months (range, 0.1 to 80.7 months) for patients who were alive at the last follow-up, the five-year overall survival (OS) and event-free survival (EFS) rate in patients without BM involvement (76.3% and 67.5%, p<0.001) was statistically higher than that in patients with BM involvement (44.3% and 40.1%, p<0.001). In multivariate analysis, among total patients, BM involvement showed a significant association with OS and EFS. In univariate and multivariate analyses, even among stage IV patients, a significant association with worse EFS was observed in the BM involvement group.
CONCLUSION
BM involvement at diagnosis affected the survival of patients with DLBCL who received RCHOP. Although use of RCHOP can result in significant improvement of the therapeutic effect of DLBCL, BM involvement is still a negative prognostic factor of DLBCL patients in the era of rituximab.

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Combination of Bone Marrow Biopsy and Flow Cytometric Analysis: The Prognostically Relevant Central Approach for Detecting Bone Marrow Invasion in Diffuse Large B-Cell Lymphoma
Haruya Okamoto, Nobuhiko Uoshima, Ayako Muramatsu, Reiko Isa, Takahiro Fujino, Yayoi Matsumura-Kimoto, Taku Tsukamoto, Shinsuke Mizutani, Yuji Shimura, Tsutomu Kobayashi, Eri Kawata, Hitoji Uchiyama, Junya Kuroda
Diagnostics.2021; 11(9): 1724. CrossRef
Assessment of CD52 expression in "double-hit" and "double-expressor" lymphomas: Implications for clinical trial eligibility
Jeffrey W. Craig, Michael J. Mina, Jennifer L. Crombie, Ann S. LaCasce, David M. Weinstock, Geraldine S. Pinkus, Olga Pozdnyakova, Francesco Bertolini
PLOS ONE.2018; 13(7): e0199708. CrossRef
HIV-infection impact on clinical–biological features and outcome of diffuse large B-cell lymphoma treated with R-CHOP in the combination antiretroviral therapy era
Maria Joao Baptista, Olga Garcia, Mireia Morgades, Eva Gonzalez-Barca, Pilar Miralles, Armando Lopez-Guillermo, Eugenia Abella, Miriam Moreno, Juan-Manuel Sancho, Evarist Feliu, Josep-Maria Ribera, Jose-Tomas Navarro
AIDS.2015; 29(7): 811. CrossRef
Non-Hodgkin Lymphomas: Impact of Rituximab on Overall Survival of Patients with Diffuse Large B-Cell and Follicular Lymphoma
José Carlos Jaime-Pérez, Carmen Magdalena Gamboa-Alonso, Alberto Vázquez-Mellado de Larracoechea, Marisol Rodríguez-Martínez, César Homero Gutiérrez-Aguirre, Luis Javier Marfil-Rivera, David Gómez-Almaguer
Archives of Medical Research.2015; 46(6): 454. CrossRef

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Expression of Transforming Growth Factor beta1 and E-Cadherin Proteins in Pulmonary Adenocarcinoma: Its Significance in Tumor Progression: Chi Hong Kim, Sonya Youngju Park, Jinyoung Yoo; Cancer Res Treat. 2013;45(2):118-125. Published online June 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.2.118

Abstract PDF PubReader ePub

PURPOSE
This study was conducted in order to investigate the significance of transforming growth factor beta1 (TGFbeta1) and E-cadherin proteins in tumor progression of lung adenocarcinoma and to evaluate their differential expression in association with morphologic characteristics.
MATERIALS AND METHODS
A total of 65 pulmonary adenocarcinomas were reclassified according to the new classification system proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, and European Respiratory Society. Tumor samples from 20 adenocarcinomas in situ (AIS, formerly bronchioloalveolar carcinoma [BAC]), 9 minimally invasive adenocarcinomas (MIA, formerly BAC with < or = 5 mm invasion), 17 lepidic predominant adenocarcinomas (LPA, formerly mixed adenocarcinoma showing nonmucinous BAC features with >5 mm invasion), and 19 invasive adenocarcinomas with no BAC features were analyzed by immunohistochemistry for expression of TGFbeta1 and E-cadherin proteins.
RESULTS
TGFbeta1 expression was detected in 46% (21/46) of noninvasive elements and 87% (39/45) of invasive elements (p=0.001). E-Cadherin expression was less frequent in invasive components than in noninvasive components (38% vs. 65%, p=0.009). Negative correlation was identified between TGFbeta1 expression and E-cadherin expression in noninvasive elements (p=0.022). More importantly, significantly higher frequency of TGFbeta1 expression was observed in noninvasive components of LPA (14/17, 82%), compared with those of either AIS (5/20, 25%) or MIA (2/9, 22%) (p=0.008).
CONCLUSION
Our data indicate involvement of both TGFbeta1 and E-cadherin proteins in tumor progression of pulmonary adenocarcinoma. It is noteworthy that TGFbeta1 up-regulation precedes alveolar destruction by invasion of tumor cells. TGFbeta1 may thus have the potential to improve lung adenocarcinoma diagnostics and therapeutics.

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Aberrant N-cadherin expression in cancer
Zhan-Qi Cao, Zhi Wang, Ping Leng
Biomedicine & Pharmacotherapy.2019; 118: 109320. CrossRef
High FDG uptake on PET is associated with negative cell-to-cell adhesion molecule E-cadherin expression in lung adenocarcinoma
Kotaro Higashi, Yoshimichi Ueda, Miyako Shimasaki, Yasuhito Ishigaki, Yuka Nakamura, Manabu Oguchi, Tsutomu Takegami, Naoto Watanabe
Annals of Nuclear Medicine.2017; 31(8): 590. CrossRef
17‐AAG suppresses growth and invasion of lung adenocarcinoma cells via regulation of the LATS1/YAP pathway
Xiang‐Yun Ye, Qing‐Quan Luo, Yun‐Hua Xu, Nai‐Wang Tang, Xiao‐Min Niu, Zi‐Ming Li, Sheng‐Ping Shen, Shun Lu, Zhi‐Wei Chen
Journal of Cellular and Molecular Medicine.2015; 19(3): 651. CrossRef
F-box protein complex FBXL19 regulates TGFβ1-induced E-cadherin down-regulation by mediating Rac3 ubiquitination and degradation
Su Dong, Jing Zhao, Jianxin Wei, Rachel K Bowser, Andrew Khoo, Zhonghui Liu, James D Luketich, Arjun Pennathur, Haichun Ma, Yutong Zhao
Molecular Cancer.2014;[Epub] CrossRef
High p-Smad2 expression in stromal fibroblasts predicts poor survival in patients with clinical stage I to IIIA non-small cell lung cancer
Yongbing Chen, Pengfei Xing, Yuanyuan Chen, Li Zou, Yongsheng Zhang, Feng Li, Xueguan Lu
World Journal of Surgical Oncology.2014;[Epub] CrossRef
Brain Metastases from Lung Cancer Show Increased Expression of DVL1, DVL3 and Beta-Catenin and Down-Regulation of E-Cadherin
Anja Kafka, Davor Tomas, Vili Beroš, Hrvoje Pećina, Martina Zeljko, Nives Pećina-Šlaus
International Journal of Molecular Sciences.2014; 15(6): 10635. CrossRef
TGF-β Suppresses COX-2 Expression by Tristetraprolin-Mediated RNA Destabilization in A549 Human Lung Cancer Cells
Soyeong Kang, Ahrum Min, Seock-Ah Im, Sang-Hyun Song, Sang Gyun Kim, Hyun-Ah Kim, Hee-Jun Kim, Do-Youn Oh, Hyun-Soon Jong, Tae-You Kim, Yung-Jue Bang
Cancer Research and Treatment.1970; 47(1): 101. CrossRef

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Src Family Kinase Inhibitor PP2 Has Different Effects on All-Trans-Retinoic Acid or Arsenic Trioxide-Induced Differentiation of an Acute Promyelocytic Leukemia Cell Line: Suk-Gu Yoon, Hee-Jeong Cheong, Sook-Ja Kim, Kyoung Ha Kim, Sang-Cheol Lee, Namsu Lee, Hee Sook Park, Jong-Ho Won; Cancer Res Treat. 2013;45(2):126-133. Published online June 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.2.126

Abstract PDF PubReader ePub

PURPOSE
Leukemic promyelocytes have the unique ability to undergo differentiation after exposure to retinoic acid and both differentiation and apoptosis after exposure to arsenic trioxide (ATO). Recent studies have shown that inhibition of Src family kinases (SFKs) resulted in enhancement of retinoic acid-induced myeloid differentiation.
MATERIALS AND METHODS
In this study, we investigated the question of whether the SFK inhibitor PP2 enhanced the differentiation of NB4 cells when combined with ATO as well as when combined with all-trans-retinoic acid (ATRA). In addition, we attempted to determine the difference in retinoic acid-induced gene expression between cells treated with PP2 in combination with ATRA and in combination with ATO.
RESULTS
SFK inhibitor PP2 induced significant enhancement of ATRA- or ATO-induced differentiation of NB4 cells. A significantly stronger synergistic effect was observed when PP2 was combined with ATRA than when combined with ATO. Flow cytometric analysis demonstrated a significant increase in CD11b-positive granulocytes up to 60.73% and 31.58%, respectively. These results were confirmed by nitroblue tetrazolium staining. These effects were not related to apoptosis. Results of Annexin-V-fluorescein staining revealed that PP2 combined with ATRA or PP2 combined with ATO did not induce apoptosis in NB4 cells. Retinoic acid-induced gene expression was different in both groups. Intercellular adhesion molecule-1 expression showed a significant increase in cells treated with PP2 in combination with ATRA, whereas cathepsin D expression showed a significant increase in cells treated with PP2 in combination with ATO.
CONCLUSION
Our data showed that SFK inhibitor PP2 enhanced acute promyelocytic leukemia cell differentiation when combined with either ATRA or ATO with difference in activation of retinoic acid-induced genes.

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An overview of arsenic trioxide-involved combined treatment algorithms for leukemia: basic concepts and clinical implications
Yanan Jiang, Xiuyun Shen, Fengnan Zhi, Zhengchao Wen, Yang Gao, Juan Xu, Baofeng Yang, Yunlong Bai
Cell Death Discovery.2023;[Epub] CrossRef
Integrated bioinformatics analysis and network pharmacology to explore the potential mechanism of Patrinia heterophylla Bunge against acute promyelocytic leukemia
Liya Feng, Sha Zhu, Jian Ma, Yali Hong, Meixia Wan, Qian Qiu, Hongjing Li, Juan Li
Medicine.2023; 102(40): e35151. CrossRef
Serum levels of FAK and some of its effectors in adult AML: correlation with prognostic factors and survival
Mona G. El-Sisi, Sara M. Radwan, Alia M. Saeed, Hala O. El-Mesallamy
Molecular and Cellular Biochemistry.2021; 476(5): 1949. CrossRef
O-GlcNAc homeostasis contributes to cell fate decisions during hematopoiesis
Zhen Zhang, Matthew P. Parker, Stefan Graw, Lesya V. Novikova, Halyna Fedosyuk, Joseph D. Fontes, Devin C. Koestler, Kenneth R. Peterson, Chad Slawson
Journal of Biological Chemistry.2019; 294(4): 1363. CrossRef
Src family kinases and their role in hematological malignancies
Matthew Ku, Meaghan Wall, Ruth N. MacKinnon, Carl R. Walkley, Louise E. Purton, Constantine Tam, David Izon, Lynda Campbell, Heung-Chin Cheng, Harshal Nandurkar
Leukemia & Lymphoma.2015; 56(3): 577. CrossRef
Hematopoietic cell kinase (HCK) as a therapeutic target in immune and cancer cells
Ashleigh R. Poh, Robert J.J. O’Donoghue, Matthias Ernst
Oncotarget.2015; 6(18): 15752. CrossRef
Src family kinase inhibitor PP2 enhances differentiation of acute promyelocytic leukemia cell line induced by combination of all-trans-retinoic acid and arsenic trioxide
Yun Seok Jung, Hee-Jeong Cheong, Sook-Ja Kim, Kyoung Ha Kim, Namsu Lee, Hee Sook Park, Jong-Ho Won
Leukemia Research.2014; 38(8): 977. CrossRef

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RASSF1A Suppresses Cell Migration through Inactivation of HDAC6 and Increase of Acetylated alpha-Tubulin: Hae-Yun Jung, Jun Seok Jung, Young Mi Whang, Yeul Hong Kim; Cancer Res Treat. 2013;45(2):134-144. Published online June 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.2.134

Abstract PDF PubReader ePub

PURPOSE
The RAS association domain family protein 1 (RASSF1) has been implicated in a tumor-suppressive function through the induction of acetylated alpha-tubulin and modulation of cell migration. However, the mechanisms of how RASSF1A is associated with acetylation of alpha-tubulin for controlling cell migration have not yet been elucidated. In this study, we found that RASSF1A regulated cell migration through the regulation of histon deacetylase 6 (HDAC6), which functions as a tubulin deacetylase.
MATERIALS AND METHODS
The cell migration was assessed using wound-healing and transwell assays. The role of RASSF1A on cell migration was examined by immunofluorescence staining, HDAC activity assay and western blot analysis.
RESULTS
Cell migration was inhibited and cell morphology was changed in RASSF1A-transfected H1299 cells, compared with controls, whereas HDAC6 protein expression was not changed by RASSF1A transfection in these cells. However, RASSF1A inhibited deacetylating activity of HDAC6 protein and induced acetylated alpha-tubulin expression. Furthermore, acetylated alpha-tubulin and HDAC6 protein were co-localized in the cytoplasm in RASSF1A-transfected H1299 cells. Conversely, when the endogenous RASSF1A expression in HeLa cells was blocked with RASSF1A siRNA treatment, acetylated alpha-tubulin was co-localized with HDAC6 protein throughout the whole cells, including the nucleus, compared with scramble siRNA-treated HeLa cells. The restoration of RASSF1A by 5-Aza-dC treatment also induced acetylated alpha-tubulin through inhibition of HDAC6 activity that finally resulted in suppressing cell migration in H1299 cells. To further confirm the role of HDAC6 in RASSF1A-mediated cell migration, the HDAC6 expression in H1299 cells was suppressed by using HDAC6 siRNA, and cell motility was found to be decreased through enhanced acetylated alpha-tubulin.
CONCLUSION
The results of this study suggest that the inactivation of HDAC6 by RASSF1A regulates cell migration through increased acetylated alpha-tubulin protein.

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Luojia Liu, Xiaoqiang Liu, Ying Chen, Meng Kong, Jinghong Zhang, Min Jiang, Hongling Zhou, Jinrui Yang, Xu Chen, Ze Zhang, Chao Wu, Xupin Jiang, Jiaping Zhang
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European Journal of Cell Biology.2022; 101(2): 151202. CrossRef
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Autophagy.2020; 16(10): 1753. CrossRef
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Hyuk-Joon Jeon, Jeong Su Oh
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Zsofia Kutil, Lubica Skultetyova, David Rauh, Marat Meleshin, Ivan Snajdr, Zora Novakova, Jana Mikesova, Jiri Pavlicek, Martin Hadzima, Petra Baranova, Barbora Havlinova, Pavel Majer, Mike Schutkowski, Cyril Barinka
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Wenjiao Li, Fei Yue, Yuan Dai, Boyun Shi, Guibin Xu, Xianhan Jiang, Xinke Zhou, Gerd P. Pfeifer, Leyuan Liu
Cell Death & Differentiation.2019; 26(8): 1379. CrossRef
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Mohammad Reza Zinatizadeh, Seyed Ali Momeni, Peyman Kheirandish Zarandi, Ghanbar Mahmoodi Chalbatani, Hassan Dana, Hamid Reza Mirzaei, Mohammad Esmaeil Akbari, Seyed Rouhollah Miri
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Fatéméh Dubois, Emmanuel Bergot, Gérard Zalcman, Guénaëlle Levallet
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Hiroaki Iwasa, Shakhawoat Hossain, Yutaka Hata
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Dual-functionality of RASSF1A overexpression in A375 cells is mediated by activation of IL-6/STAT3 regulatory loop
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Case Reports

Two Cases of Humoral Hypercalcemia of Malignancy in Metastatic Cholangiocarcinoma: Seungtaek Lim, Jungwoo Han, Kyeong Hye Park, Won Jai Jung, Yong Kang Lee, Ara Choi, Young Jae Kim, Jong-Chan Lee, Hye Jin Choi; Cancer Res Treat. 2013;45(2):145-149. Published online June 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.2.145

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Humoral hypercalcemia of malignancy (HHM) is rarely associated with cholangiocarcinoma (CC), and represents dismal prognosis. A 63-year-old male was admitted for evaluation of an intrahepatic mass. He was diagnosed with HHM associated with locally advanced CC. As the tumor responded to the concurrent chemoradiotherapy with capecitabine and cisplatin, serum calcium level was normalized. However, according to the disease progression, he suffered recurrence of HHM and he expired approximately one year after initial diagnosis. A 68-year-old male who presented with abdominal pain was diagnosed with metastatic CC. After the eighth cycle of gemcitabine and cisplatin, progression of the disease was found with HHM. He was treated with the best supportive care, until his demise approximately one month after the diagnosis of HHM. We report on two cases of HHM associated with CC that demonstrate strong correlation between hypercalcemia and disease burden.

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The peculiar clinical presentation and diagnostic results of a case of widely metastatic cholangiocellular carcinoma in a Siberian Husky dog
Hannah Reichert, Alexandra Macleod, Leslie Sharkey, Cornelia Peterson
Topics in Companion Animal Medicine.2024; 63: 100923. CrossRef
Prevalence and Clinicopathologic Characteristics of Hypercalcemia in Patients With Cholangiocarcinoma
Eirini Konstantinidou, Jordan R. Maurer, Stephanie L. Reyes, Islam Baiev, Jennifer R. Stanton, Ryan D. Nipp, Lipika Goyal
JAMA Oncology.2023; 9(5): 714. CrossRef
Recurrent distal cholangiocarcinoma and humoral hypercalcemia of malignancy: report of a rare case and literature review
Jun Ito, Kiten Sakai, Yuki Yamamoto, Rikako Nakajima, Kei Ito, Masanao Fujii, Hideki Matsumura, Norio Takayashiki, Masanao Kurata, Satoshi Inagawa, Hiroaki Yagyu
Endocrine Journal.2023; 70(4): 375. CrossRef
Hypercalcemia of Malignancy in a Dog Diagnosed With Cholangiocellular Carcinoma
Laura Martínez-Sogues, Anna Vila, Xavier Roura, Josep Pastor, Rosa Novellas, Alberto Marco, Maria Cuvertoret-Sanz, Jorge Martínez, Laia Solano-Gallego
Topics in Companion Animal Medicine.2019; 35: 1. CrossRef
Combined Hepatocholangiocarcinoma Associated with Humoral Hypercalcemia of Malignancy and Chronic Inflammatory Demyelinating Polyneuropathy
Ruben Manuel Luciano Colunga Biancatelli, Marco Ciacciarelli, Alessandro Polidoro, Piera Clemenzi, Viviana Congedo, Leonardo Calvosa, Eleonora D’Armiento, Carmen Misurale, Davide Bellini, Stefano Badia, Massimiliano Mancini, Vincenzo Petrozza, Luigi Iulia
Case Reports in Oncological Medicine.2019; 2019: 1. CrossRef
Humoral Hypercalcemia of Malignancy with a Parathyroid Hormone-Related Peptide-Secreting Intrahepatic Cholangiocarcinoma Accompanied by a Gastric Cancer
Katsushi Takeda, Ryosuke Kimura, Nobuhiro Nishigaki, Shinya Sato, Asami Okamoto, Kumiko Watanabe, Sachie Yasui
Case Reports in Endocrinology.2017; 2017: 1. CrossRef
Denosumab is Effective for Controlling Serum Calcium Levels in Patients with Humoral Hypercalcemia of Malignancy Syndrome: A Case Report on Parathyroid Hormone-related Protein-producing Cholangiocarcinoma
Norihiro Ashihara, Koji Nakajima, Yoshiyuki Nakamura, Mutsuhiro Kobayashi, Kumiko Shirahata, Chika Maeda, Takeshi Uehara, Daisuke Gomi, Nobuo Ito
Internal Medicine.2016; 55(23): 3453. CrossRef
Esophageal Cancer Initially Presenting as Severe Paraneoplastic Hypercalcemia Requiring Hemodialysis
Hye Shin Ahn, Jong Min Yun, Yeong Bok Lee, Yu Mi Ko, Jung Eun Lee, Hye Sung Won, Sung Soo Kim, Young Ok Kim
The Korean Journal of Gastroenterology.2015; 65(6): 361. CrossRef

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Multiple Cardiac Metastases from a Nonfunctioning Pancreatic Neuroendocrine Tumor: Yong Hyeok Choi, Hye-Suk Han, Sung-Nam Lim, Sang Yeub Lee, Ji Hae Koo, Ok-Jun Lee, Ki Hyeong Lee, Seung Taik Kim; Cancer Res Treat. 2013;45(2):150-154. Published online June 30, 2013; DOI: https://doi.org/10.4143/crt.2013.45.2.150

Abstract PDF PubReader ePub

Pancreatic neuroendocrine tumors (pNETs) are rare neoplasms, which most commonly metastasize to the liver. However, intrathoracic metastases from pNETs are encountered infrequently. This report describes a case of nonfunctioning pNET with multiple cardiac metastases. A 56-year-old male presented with a palpable abdominal mass that showed progressive enlargement. Findings on computed tomography (CT) of the abdomen revealed two relatively well-marginated inhomogeneous low-attenuation masses, one in the head of the pancreas and the other in the tail. Multiple enhancing masses in the left pericardium with myocardial involvement were observed on chest CT and transthoracic echocardiography. Needle biopsies were performed on the mass in the tail of the pancreas and the left ventricular apical pericardium; histologic examination by hematoxylin and eosin morphology and immunohistochemical staining showed pNET in both. This is the first report of pNET with multiple cardiac metastases to previously undescribed metastatic sites.

Citations

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Journal of Nuclear Medicine.2024; 65(11): 1745. CrossRef
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Medicina.2021; 57(2): 107. CrossRef
Cardiac Metastases in Patients with Neuroendocrine Tumours: Clinical Features, Therapy Outcomes, and Prognostic Implications
Man Liu, Eleni Armeni, Shaunak Navalkissoor, Joseph Davar, Luke Sullivan, Charlotte Leigh, Luke Furtado O’Mahony, Aimee Hayes, Dalvinder Mandair, Jie Chen, Martyn Caplin, Christos Toumpanakis
Neuroendocrinology.2021; 111(10): 907. CrossRef
A concealed carcinoid cardiac metastasis uncovered by comprehensive cardiovascular magnetic resonance-based tissue characterization: a case report
Georgios Georgiopoulos, Panagiota Mitropoulou, Pier Giorgio Masci, Juerg Schwitter, Khan Tina, Voges Inga, Raisi Estabragh Zahra, Minguito Carazo Carlos, Thomson Ross
European Heart Journal - Case Reports.2020; 4(6): 1. CrossRef
A Multimodal Approach to Evaluate for Cardiac Metastasis in a Case of Non-Small Cell Lung Cancer
Nadeem Bilani, Leah Elson, Felipe Martinez, Diego Sadler, Zeina Nahleh, Elizabeth Elimimian, Evan Alley
Case Reports in Oncology.2020; 13(1): 212. CrossRef
Identification of multiple cardiac metastases from nonsmall-cell lung cancer by 18F-FDG PET/CT
Shengming Deng, Bin Zhang, Jihui Li, Shibiao Sang, Wei Zhang
Medicine.2018; 97(49): e12868. CrossRef

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