Ai zheng = Aizheng = Chinese journal of cancer (Chin J Canc)

Publications in this journal

• Article: Urinary bladder malignant paraganglioma with vertebral metastasis: a case report with review of the literature.

  Ning Feng, Xiang Li, Haide Gao, Zhong-Lin Liu, Lu-Jing Shi, Wen-Zhi Liu
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  ABSTRACT: Paraganglioma (also known as extra-adrenal pheochromocytoma) is a rare neuroendocrine neoplasm observed in patients of all ages, with an estimated incidence of 1 per 300,000 population. It has long been recognized that some cases are familial. The majority of these tumors are benign, and the only absolute criterion for malignancy is the presence of metastases at sites where chromaffin tissue is not usually found. Some tumors show gross local invasion and recurrence, which may indeed kill the patient, but this does not necessarily correlate with metastatic potential. Here, we report a case of vertebral metastatic paraganglioma that occurred 19 months after the patient had undergone partial cystectomy for urinary bladder paraganglioma. We believe this to be a rarely reported bone metastasis of paraganglioma arising originally within the urinary bladder. In this report, we also provide a summary of the general characteristics of this disease, together with progress in diagnosis, treatment, and prognosis.
  Ai zheng = Aizheng = Chinese journal of cancer 05/2013;
• Article: Dysregulation of mTOR activity through LKB1 inactivation.

  Wei Zhou, Adam I Marcus, Paula Vertino
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  ABSTRACT: Mammalian target of Rapamycin (mTOR) is aberrant activated in many cancer types, and two Rapamycin derivatives are currently approved by FDA for the treatment of renal cell carcinoma. Mechanistically, mTOR is hyperactivated in human cancers either due to the genetic activation of its upstream activating signaling pathways or the genetic inactivation of its negative regulators. The tumor suppressor liver kinase B1 (LKB1; also known as serine/threonine kinase 11, STK11) involves in cell polarity, cell detachment and adhesion, tumor metastasis, and energetic stress response. One of LKB1's key roles is to negatively regulate mTOR complex 1 (mTORC1) activity. This review summarizes the molecular basis of this negative interaction, and recent research progress in this area.
  Ai zheng = Aizheng = Chinese journal of cancer 05/2013;
• Article: Intraarterial chemotherapy with gemcitabine and cisplatin in locally advanced or recurrent squamous cell carcinoma of the penis.

  Jian-Ye Liu, Yong-Hong Li, Zhou-Wei Liu, Zhi-Ling Zhang, Yun-Lin Ye, Kai Yao, Hui Han, Zi-Ke Qin, Fang-Jian Zhou
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  ABSTRACT: The prognosis of locally advanced or recurrent squamous cell carcinoma (SCC) of the penis after conventional treatment is dismal. This study aimed to evaluate the therapeutic effects of intraarterial chemotherapy with gemcitabine and cisplatin in patients with locally advanced or recurrent SCC of the penis. Between April 1999 and May 2011, we treated five patients with locally advanced penile SCC and seven patients with recurrent disease with intraarterial chemotherapy. The response rate and toxicity data were retrospectively analyzed, and survival rates were calculated. After two to six cycles of intraarterial chemotherapy with gemcitabine and cisplatin, one out of five patients with locoregionally advanced disease achieved a complete response (CR), and four patients achieved partial response (PR). Of the seven patients with recurrent disease, two achieved CR, three patients achieved PR, one achieved stable disease, and the other one developed progressive disease. An objective tumor response was therefore achieved in 10 of the 12 patients. The median interval of overall survival for the patients was 24 months (range: 10-50 months). Three out of 10 patients who responded were long-term survivors after intraarterial chemotherapy. Intraarterial chemotherapy with gemcitabine and cisplatin may be effective and potentially curative in locoregionally advanced or recurrent penile SCC. The contribution of this therapy in the primary management of advanced or recurrent penile SCC should be prospectively investigated.
  Ai zheng = Aizheng = Chinese journal of cancer 05/2013;
• Article: Molecular mechanisms of tumor resistance to PI3K-mTOR targeted cancer therapy.

  Jing Tan, Qiang Yu
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  ABSTRACT: Deregulation of the phosphatidylinositide 3-kinase (PI3K) and mammalian target of rapamycin (mTOR) signaling pathway occurs frequently in a wide range of human cancers and is a major driving force in tumorigenesis. Thus, small molecules targeting this pathway are under active development as anti-cancer therapeutics. Although small molecule inhibitors of the PI3K-mTOR pathway have shown promising clinical efficacy against human cancers, the emergence of drug resistance may limit their success in the clinic. To date, several resistance mechanisms, including both PI3K-dependent and-independent mechanisms, have been described. Here, we summarize the current understanding of resistance mechanisms to PI3K-mTOR inhibitors and discuss potential strategies for overcoming resistance for potential clinical application.
  Ai zheng = Aizheng = Chinese journal of cancer 05/2013;
• Article: Clinical implications of miRNAs in liver cancer stem cells.

  Stella Chai, Stephanie Ma
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  ABSTRACT: The prognosis of patients diagnosed with hepatocellular carcinoma (HCC) is often dismal mainly due to late presentation, high recurrence rate and the disease's resistance to chemotherapy and radiotherapy. Accumulating evidence on the differential microRNA (miRNA) expression patterns between non-tumor and HCC or liver cancer stem cells (CSC) and non-CSC subsets, and their significant clinical implications, has suggested miRNA to be a promising, non-invasive marker for the prognosis and diagnosis of the disease. This perspective article provides a summary of the current knowledge of miRNAs in liver CSCs and points to the need of further investigating the role of miRNAs in regulating liver CSC subsets for possible future clinical applications.
  Ai zheng = Aizheng = Chinese journal of cancer 05/2013;
• Article: Molecular targeted agents--where we are and where we are going.

  Li Yan
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  ABSTRACT: A total of 23 new cancer medicines or indication expansions were approved by the U. S. Food and Drug Administration in 2012. Among these, 12 are new molecular entities (NMEs)--new chemical or biological drugs approved for the first time for oncologic use--and 10 of these NMEs are molecular targeted agents. Among the 10 targeted agents, 4 are anti-angiogenesis agents and 2 are Bcr-Abl pathway inhibitors, targeting well established targets validated by previously approved agents such as bevacizumab (Avastin) or imatinib (Gleevec). Despite this progress, several questions remain: Do these newly approved agents provide sufficient treatment options to manage the broad spectrum of cancers we deal with in the clinic? Where will the next wave of new cancer drugs come from? Where should R&D efforts be invested to continue improve cancer treatment and management, especially for tumor types uniquely prevalent in China? This editorial and the review articles in this special issue of Chinese Journal of Cancer provide an in depth review of the progress and challenges in developing targeted cancer therapies, as well as an outlook of new research areas where near term breakthroughs are expected to overcome some of these challenges.
  Ai zheng = Aizheng = Chinese journal of cancer 05/2013; 32(5):225-32.
• Article: Targeting the PI3K-AKT-mTOR signaling network in cancer.

  Khurum H Khan, Timothy A Yap, Li Yan, David Cunningham
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  ABSTRACT: The phosphoinositide 3-kinase-AKT-mammalian target of rapamycin (PI3K-AKT-mTOR) pathway is a frequently hyperactivated pathway in cancer and is important for tumor cell growth and survival. The development of targeted therapies against mTOR, a vital substrate along this pathway, led to the approval of allosteric inhibitors, including everolimus and temsirolimus, for the treatment of breast, renal, and pancreatic cancers. However, the suboptimal duration of response in unselected patients remains an unresolved issue. Numerous novel therapies against critical nodes of this pathway are therefore being actively investigated in the clinic in multiple tumor types. In this review, we focus on the progress of these agents in clinical development along with their biological rationale, the need of predictive biomarkers and various combination strategies, which will be useful in counteracting the mechanisms of resistance to this class of drugs.
  Ai zheng = Aizheng = Chinese journal of cancer 05/2013; 32(5):253-65.
• Article: The recurrence and survival of oral squamous cell carcinoma: a report of 275 cases.

  Bo Wang, Shu Zhang, Kai Yue, Xu-Dong Wang
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  ABSTRACT: Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck, and recurrence is an important prognostic factor in patients with OSCC. We explored the factors associated with recurrence of OSCC and analyzed the survival of patients after recurrence. Clinicopathologic and follow-up data of 275 patients with OSCC treated by surgery in the Cancer Institute and Hospital of Tianjin Medical University between 2002 and 2006 were analyzed. Recurrence factors were analyzed with Chi-square or Fisher's exact test and multivariate analysis. The prognosis of patients after recurrence was analyzed with the Kaplan-Meier method and Log-rank test. The recurrence rate was 32.7%. The recurrence time ranged from 2 to 96 months, with a median time of 14 months. Univariate analysis showed that T stage, degree of differentiation, pN stage, flap application, resection margin, and lymphovascular invasion were factors of recurrence (P < 0.05). Multivariate analysis showed that T stage, degree of differentiation, and pN stage were independent factors of recurrence (P < 0.001). The differences in gender, age, the tumor site, region of lymph node metastasis, and perineural invasion between the recurrence and non-recurrence groups were not significant (P > 0.05). Kaplan-Meier and Log-rank tests showed that the 2- and 5-year survival rates were significantly lower in the recurrence group than in non-recurrence group (67.6% vs. 88.0%, 31.8% vs. 79.9%, P < 0.001). Therefore, to improve prognosis, we recommend extended local excision, flap, radical neck dissection, and adjuvant chemoradiotherapy for patients more likely to undergo recurrence.
  Ai zheng = Aizheng = Chinese journal of cancer 04/2013;
• Article: Biological functions of Decorin in cancer.

  Xiu-Li Bi, Wancai Yang
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  ABSTRACT: Decorin is a member of the extracellular matrix small leucine-rich proteoglycans family that exists and functions in stromal and epithelial cells. Accumulating evidence suggests that decorin affects the biology of various types of cancer by directly or indirectly targeting the signaling molecules involved in cell growth, survival, metastasis, and angiogenesis. More recent studies show that decorin plays important roles during tumor development and progression and is a potential cancer therapeutic agent. In this article, we summarize recent studies of decorin in cancer and discuss decorin's therapeutic and prognostic value.
  Ai zheng = Aizheng = Chinese journal of cancer 04/2013;
• Article: Centrifugation: an important pre-analytic factor that influences plasma microRNA quantification during blood processing.

  Xiao-Hui Zheng, Cui Cui, Xin-Xi Zhou, Yi-Xin Zeng, Wei-Hua Jia
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  ABSTRACT: Circulating microRNAs are robustly present in plasma or serum and have become a research focus as biomarkers for tumor diagnosis and prognosis. Centrifugation is a necessary factor for obtaining high-quality blood supernatant. Herein, we investigated one-step and two-step centrifugations, two centrifugal methods routinely used in microRNA study, to explore their effects on plasma microRNA quantification. The microRNAs obtained from one-step and two-step centrifugations were quantified by microarray and TaqMan-based real-time quantitative polymerase chain reaction (Q-PCR). Dynamic light scattering was performed to explore the difference underlying the two centrifugal methods. The results from the microarray containing 1,347 microRNAs showed that the signal detection rate was greatly decreased in the plasma sample prepared by two-step centrifugation. More importantly, the microRNAs missing in this plasma sample could be recovered and detected in the precipitate generated from the second centrifugation. Consistent with the results from microarray, a marked decrease of three representative microRNAs in two-step centrifugal plasma was validated by Q-PCR. According to the size distribution of all nanoparticles in plasma, there were fewer nanoparticles with size >1000 nm in two-step centrifugal plasma. Our experiments directly demonstrated that different centrifugation methods produced distinct quantities of plasma microRNAs. Thus, exosomes or protein complexes containing microRNAs may be involved in large nanoparticle formation and may be precipitated after two-step centrifugation. Our results remind us that sample processing methods should be first considered in conducting research.
  Ai zheng = Aizheng = Chinese journal of cancer 04/2013;
• Article: Germinal-center type B-cell classification and clinical characteristics of Chinese pediatric diffuse large B-cell lymphoma: a report of 76 cases.

  Yan Chen, Xiao-Fei Sun, Zi-Jun Zhen, Juan Wang, Jia Zhu, Su-Ying Lu, Fei-Fei Sun, Fei Zhang, Peng-Fei Li, Rui-Qing Cai
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  ABSTRACT: Pediatric diffuse large B-cell lymphoma (DLBCL) is a highly aggressive disease with unique clinical characteristics. This study analyzed the germinal-center type B-cell (GCB) classification and clinical characteristics of Chinese pediatric DLBCL. A total of 76 patients with DLBCL newly diagnosed in Sun Yat-sen University Cancer Center between February 2000 and May 2011, with an age younger than 18 years, were included in the analysis. The male/female ratio was 3.47. The median age was 12 years (range, 2 to 18 years), and 47 (61.8%) patients were at least 10 years old. Of the 76 patients, 48 (63.2%) had stage III/IV disease, 9 (11.8%) had bone marrow involvement, 1 (1.3%) had central nervous system (CNS) involvement, and 5 (6.6%) had bone involvement. The GCB classification was assessed in 45 patients: 26 (57.8%) were classified as GCB subtype, and 19 (42.2%) were classified as non-GCB subtype. The modified B-NHL-BFM 90/95 regimen was administered to 50 patients, and the 4-year event-free survival (EFS) rate was 85.8%. Among these 50 patients, 31 were assessed for the GCB classification: 17 (54.8%) were classified as GCB subtype, with a 4-year EFS rate of 88.2 %; 14 (45.2%) were classified as non-GCB subtype, with a 4-year EFS rate of 92.9%. Our data indicate that bone marrow involvement and stage III/IV disease are common in Chinese pediatric DLBCL patients, while the percentage of patients with the GCB subtype is similar to that of patients with the non-GCB subtype. The modified NHL-BFM-90/95 protocol is an active and effective treatment protocol for Chinese pediatric patients with DLBCL.
  Ai zheng = Aizheng = Chinese journal of cancer 04/2013;
• Article: Cancer Bioinformatics: detection of chromatin states, SNP-containing motifs, and functional enrichment modules.

  Xiaobo Zhou
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  ABSTRACT: In this editorial preface, we briefly review cancer bioinformatics and introduce the four articles in this special issue highlighting important applications of the field: detection of chromatin states; detection of SNP-containing motifs and association with transcription factor-binding sites; improvements in functional enrichment modules; and gene association studies on aging and cancer. We expect this issue to provide computer scientists, cancer biologists, and clinical doctors with a better understanding of how cancer bioinformatics can be used to identify candidate biomarkers and targets and to conduct functional analysis.
  Ai zheng = Aizheng = Chinese journal of cancer 04/2013;
• Article: A Chinese patient with relapsed and refractory Hodgkin lymphoma treated with brentuximab vedotin.

  Zhi-Gang Cao, Hong-Wei Zhou, Chao-Jin Peng, Mo Liu, Yu Du, Qing-Ming Yang
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  ABSTRACT: At present, approximately 20% of Hodgkin lymphomas (HL) are relapsed and refractory, and therapeutic methods including chemotherapy, radiotherapy, and even stem cell transplantation are unsatisfactory. Brentuximab vedotin, composed of CD30 antibody and a chemotherapeutic agent, is a new targeted drug that eradicates tumor cells by binding to the CD30 antigen on their surface. In clinical trials, the response rate and complete remission rate of this drug were 73% and 40%, respectively, for relapsed and refractory HL. Here we report a case of CD-30 positive relapsed and refractory HL that was treated with brentuximab. Before the treatment with brentuximab, the patient underwent chemotherapy, radiotherapy, and autologous stem cell transplantation. However, the disease continued to progress, affecting multiple organs and prompting symptoms such as persistent fever. After the treatment with brentuximab, the patient's condition improved. Body temperature returned to normal after four days. Lung nodules were reduced in size and number after a single course of treatment, and PET/CT showed partial remission and complete remission after three and six courses of treatment, respectively. The entire treatment process progressed smoothly, though the patient experienced some symptoms due to chemotherapy, including peripheral neuritis of the limbs, irritating dry cough, and mild increase in aminotransferase. No serious side effects were observed. The current general condition of the patient is good; the continuous complete remission has amounted to six months.
  Ai zheng = Aizheng = Chinese journal of cancer 04/2013;
• Article: A modified radiofrequency ablation approach for treating superficial lymph node metastasis in late-stage cancer patients: a case report.

  Ru-Hai Zou, Qi-Jiong Li, Ji-Liang Qiu, Ya-Di Liao
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  ABSTRACT: Patients with late-stage cancer commonly have distant lymph node metastasis; however, poor health often contraindicates surgical treatment. Although the quality of life and overall survival for these patients are low, there is neither a consensus nor a guide for treatment. Ablation technique and surrouding tissue damage are two possible reasons for limited study of radiofrequency ablation in patients with superficial distant lymph node metastasis. Here, we report two cases treated successfully with ultrasound-guided radiofrequency ablation for superficial distant lymph node metastasis. In these cases, deionized water was injected to the surrounding lymph node to decrease heat injury. Results from these cases suggest that radiofrequency ablation may play an important role in the treatment of patients with distant lymph node metastasis.
  Ai zheng = Aizheng = Chinese journal of cancer 04/2013;
• Article: Impact of genetic alterations on mTOR-targeted cancer therapy.

  Shi-Yong Sun
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  ABSTRACT: Rapamycin and its derivatives (rapalogs), a group of allosteric inhibitors of mammalian target of rapamycin (mTOR), have been actively tested in a variety of cancer clinical trials, and some have been approved by the Food and Drug Administration for the treatment of certain types of cancers. However, the single agent activity of these compounds in many tumor types remains modest. The mTOR axis is regulated by multiple upstream signaling pathways. Because the genes (e.g., PIK3CA, KRAS, PTEN, and LKB1) that encode key components in these signaling pathways are frequently mutated in human cancers, a subset of cancer types may be addicted to a given mutation, leading to hyperactivation of the mTOR axis. Thus, efforts have been made to demonstrate the potential impact of genetic alterations on rapalog-based or mTOR-targeted cancer therapy. This review will primarily summarize research advances in this direction.
  Ai zheng = Aizheng = Chinese journal of cancer 03/2013;
• Article: New evidence-based adaptive clinical trial methods for optimally integrating predictive biomarkers into oncology clinical development programs.

  Robert A Beckman, Cong Chen
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  ABSTRACT: Predictive biomarkers are important to the future of oncology; they can be used to identify patient populations who will benefit from therapy, increase the value of cancer medicines, and decrease the size and cost of clinical trials while increasing their chance of success. But predictive biomarkers do not always work. When unsuccessful, they add cost, complexity, and time to drug development. This perspective describes phases 2 and 3 development methods that efficiently and adaptively check the ability of a biomarker to predict clinical outcomes. In the end, the biomarker is emphasized to the extent that it can actually predict.
  Ai zheng = Aizheng = Chinese journal of cancer 03/2013;
• Article: Liver cancer incidence and mortality in China, 2009.

  Wan-Qing Chen, Rong-Shou Zheng, Si-Wei Zhang
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  ABSTRACT: Liver cancer is one of the most common cancers and a leading cause of cancer deaths in China. To aid the government in establishing a control plan for this disease, we provided real-time surveillance information by analyzing liver cancer incidence and mortality in China in 2009 reported by the National Central Cancer Registry. Liver cancer incidence and cases of death were retrieved from the national database using the ICD-10 topography code "C22," and crude incidence, mortality rates were calculated and stratified by sex, age, and location (urban/rural). China's population in 1982 and Segi (world) population structures were used for age-standardized rates. In cancer registration areas in 2009, the crude incidence of liver cancer was 28.71/100,000, making it the fourth most common cancer in China, third most common in males, and fifth most common in females. The crude mortality of liver cancer was 26.04/100,000, making it the second leading cause of cancer death in China and urban areas and the third leading cause in rural areas. Incidence and mortality rates were higher in males than in females and in rural areas than in urban areas. The age-specific incidence and mortality rates were relatively low among persons under age 30 but dramatically increased and peaked in the 80-84 year age group. These findings confirm that liver cancer is a common and fatal cancer in China. Primary and secondary prevention such as health education, hepatitis B virus vaccination, and early detection should be carried out both in males and females, in urban and rural areas.
  Ai zheng = Aizheng = Chinese journal of cancer 03/2013;
• Article: sMICA and its emerging role as a prognostic and diagnostic indicator in systemic malignancies besides hepatocellular carcinomas.

  Shailendra Kapoor
  Ai zheng = Aizheng = Chinese journal of cancer 03/2013;
• Article: Effect of anti-asthma Chinese medicine Chuankezhi on the anti-tumor activity of cytokine-induced killer cells.

  Jing-Jing Zhao, Ke Pan, Qi-Jing Wang, Zheng-Di Xu, De-Sheng Weng, Jian-Jun Li, Yong-Qiang Li, Jian-Chuan Xia
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  ABSTRACT: Chuankezhi (CKZ), a new Chinese medicine, plays an important role in immunoregulation. Cytokine-induced killer (CIK) cells have been commonly used for immunotherapy in recent years. In this study, we aimed to investigate the immunoregulatory effect of CKZ on CIK cells. Peripheral blood monocytes were isolated from healthy donors, and CIK cells were generated by culturing monocytes with IFN-γ, OKT3, and IL-2. Different concentrations of CKZ were added on day 2. After incubation for 14 days in culture, the anti-tumor effects of CIK cells were measured by cytotoxicity assay. Flow cytometry was used to explore the effect of CKZ on CIK cell immunophenotype, intracellular cytokine production, and apoptosis. The effect of CKZ on the anti-tumor activity of CIK cells in nude mice was also investigated. CKZ increased the proportion of CD3+CD56+ CIK cells but did not significantly change the percentage of CD4+, CD8+, or CD4+CD25+ T cells. CKZ-conditioned CIK cells showed a greater ability to kill tumor cell lines, as well as a higher frequency of IFN-γ and TNF-α production, compared with the CIK cells in the control group. CKZ also suppressed the apoptosis of CIK cells in vitro. Furthermore, CKZ combined with CIK cells had a stronger suppressive effect on tumor growth than the CIK, CKZ, or normal saline control groups in vivo. Our results indicate that CKZ enhances the anti-tumor activity of CIK cells and is a potential medicine for tumor immunotherapy.
  Ai zheng = Aizheng = Chinese journal of cancer 03/2013;