Genotypic and Phenotypic Analysis of αβ-Thalassemia in Children / 中国实验血液学杂志

OBJECTIVE@#To analyze the genotype and hematological characteristics of children with αβ-thalassemia in Shenzhen area of China.@*METHODS@#The erythrocyte parameters and hemoglobin components of the children were determined by blood routine examination and capillary electrophoresis (CE). Reverse dot blot (RDB) -polymerase chain reaction (PCR) was used to determine gene mutations in α- and β-thalassemia children. The Gap-PCR was used to determine the gene deletion of α-thalassemia children，while specimens suspected HKαα were determined with nested PCR.@*RESULTS@#Total of 29 complex genotypes were detected from 74 cases of αβ-thalassemia, among which 1 case was determined as β-thalassemia with αααanti4.2/αα and 5 cases were double heterozygous β-thalassemia combining α-thalassemia with intermediate phenotype. 1 case of β-28/βcap+40-43 double heterozygotes combined with --/αα and the other 62 cases were characterized by light β-thalassemia, 2 cases ofβCAP+40-43/βN with --/αα showed light α-thalassemia.@*CONCLUSION@#The genotypes of αβ-thalassemia in Shenzhen area of China are complex and diverse. The common complex genotypes are similar to those of simple β-thalassemia. If the genotype and phenotype are not consistent, the existence of rare genotype should be considered.

CCR6 Is a Predicting Biomarker of Radiosensitivity and Potential Target of Radiosensitization in Rectal Cancer / Journal of the Korean Cancer Association, 대한암학회지

PURPOSE: This study aimed to explore the functions and mechanisms of C-C motif chemokine receptor 6 (CCR6), a gene associated with progression and metastasis of colorectal cancer (CRC), in radiosensitivity of rectal cancer (RC). MATERIALS AND METHODS: RNA sequencing and immunohistochemical analysis on CCR6 expression were performed in pretreatment tissues of RC patients exhibiting different therapeutic effects of radiotherapy. Colonogenic survival assay was conducted in different CRC cell lines to assess their radiosensitivity. And the impact of CCR6 expression on radiosensitivity was validated through RNA interference. The DNA damage repair (DDR) abilities of cell lines with different CCR6 expression were evaluated through immunofluorescence-based γH2AX quantification. RESULTS: The CCR6 mRNA level was higher in patients without pathologic complete remission (pCR) than in those with pCR (fold changed, 2.11; p=0.004). High-level expression of CCR6 protein was more common in the bad responders than in the good responders (76.3% vs. 37.5%, p < 0.001). The CRC cell lines with higher CCR6 expression (LoVo and sw480) appeared to be more radioresistant, compared with the sw620 cell line which had lower CCR6 expression. CCR6 knockdown made the LoVo cells more sensitive to ionizing radiation (sensitization enhancement ratio, 1.738; p < 0.001), and decreased their DDR efficiency. CONCLUSION: CCR6 might affect the RC radiosensitivity through DDR process. These findings supported CCR6 as a predicting biomarker of radiosensitivity and a potential target of radiosensitization for RC patients.

RITA combined with temozolomide inhibits the proliferation of human glioblastoma U87 cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the effect of RITA, a small molecule that targets p53, combined with temozolomide (TMZ) on proliferation, colony formation and apoptosis of human glioblastoma U87 cells and explore the underlying mechanism.</p><p><b>METHODS</b>Cultured U87 cells were treated with RITA (1, 5, 10, 20 µmol/L), TMZ, or RITA+TMZ (half dose) for 24, 48 or 72 h. MTS assay were used to detect the cell proliferation, and the cell proliferation rate and inhibitory rate were calculated. The effect of combined treatments was evaluated by the q value. The expressions of p53, p21 and other apoptosis-associated genes were detected by qRT-PCR and Western blotting; cell apoptosis was assayed using flow cytometry with Annexin V/PI double staining; colony formation of the cells was detected with crystal violet staining.</p><p><b>RESULTS</b>MTS assay showed that RITA at the 4 doses more potently inhibited U87 cell viability than TMZ at 72 h (P=0.000) with inhibitory rates of 25.94%-41.38% and 3.84%-8.20%, respectively. RITA combined with TMZ caused a more significant inhibition of U87 cells (29.21%-52.11%) than RITA (P<0.01) and TMZ (P=0.000) alone. At the doses above 5 µmol/L, the combined treatments with RITA+TMZ for 48 h resulted in q values exceeding 1.2 and showed an obvious synergistic effect of the drugs. Both RITA and TMZ, especially the latter, significantly increased the expressions of p53, p21, puma, and other apoptosis-associated genes to accelerate apoptosis and inhibit the growth and colony formation of U87 cells, and the effect was more obvious with a combined treatment.</p><p><b>CONCLUSION</b>RITA inhibits the growth of human glioblastoma cells and enhance their sensitivity to TMZ by up-regulating p53 expression, and when combined, RITA and TMZ show a synergistic effect to cause a stronger cell inhibition.</p>

Impact of primary tumor volume and location on the prognosis of patients with locally recurrent nasopharyngeal carcinoma / 癌症

<p><b>INTRODUCTION</b>The properties of a tumor itself were considered the main factors determining the survival of patients with locally recurrent nasopharyngeal carcinoma (NPC) treated with intensity-modulated radiotherapy (IMRT). However, recurrent tumors were mainly evaluated by using the American Joint Committee on Cancer staging system, which was modeled on primary tumors and did not incorporate the tumor volume. This study aimed to investigate the prognostic values of the primary tumor location and tumor volume, and to determine whether evaluating these parameters could improve the current staging system.</p><p><b>METHODS</b>Magnetic resonance (MR) images for 229 patients with locally recurrent NPC who underwent IMRT were analyzed retrospectively.</p><p><b>RESULTS</b>The skull base, parapharyngeal space, and intracranial cavity were the most common sites of tumors. There was a difference in the survival between patients with T1 and T2 diseases (77.6% vs. 50.0%, P<0.01) and those with T3 and T4 diseases (33.0% vs. 18.0%, P=0.04) but no difference between patients with T2 and T3 diseases (50.0% vs. 33.0%, P=0.18). Patients with a tumor volume≤38 cm3 had a significantly higher survival rate compared with those with a tumor volume>38 cm3 (48.7% vs. 15.2%, P<0.01).</p><p><b>CONCLUSIONS</b>A new staging system has been proposed, with T3 tumors being down-staged to T2 and with the tumor volume being incorporated into the staging, which may lead to an improved evaluation of these tumors. This new system can be used to guide the treatment strategy for different risk groups of recurrent NPC.</p>

International collaborations preparing for a cancer "moon shot": a summary of the Sino-US Symposium on Head and Neck Cancer / 癌症

Oncologists and scientists in the field of head and neck cancer exchanged their research findings and clinical experiences in the Sino-USA Symposium on Head and Neck Cancer, which was held January 6-7, 2012 in Guangzhou, China. The symposium was jointly organized by Sun Yat-sen University Cancer Center (SYSUCC) and the University of Texas MD Anderson Cancer Center (MDACC). The Guangdong Provincial Anti-Cancer Association and the Chinese Journal of Cancer also helped in organizing the conference. Speakers were from China (SYSUCC, the Chinese University of Hong Kong, Tianjin Medical University Cancer Institute and Hospital, and Fudan University Shanghai Cancer Center) and the United States (MDACC). The presentations covered most kinds of head and neck cancers and included both basic and clinical research progress. In particular, NPC was discussed in depth. The symposium explored the reality that cancer is complex and numerous questions remain to be answered, even though there has already been an enormous effort into research. International exchanges of experience and in-depth cooperation are definitely needed to improve our capability of caring for cancer patients. In this article, we provide highlights of the presentations.

Treatment outcomes for different subgroups of nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy / 癌症

Although many studies have investigated intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC), sample sizes in the reported studies are usually small and different in outcomes in different T and N subgroups are seldom analyzed. Herein, we evaluated the outcomes of NPC patients treated with IMRT and further explored treatment strategy to improve such outcome. We collected clinical data of 865 NPC patients treated with IMRT alone or in combination with chemotherapy, and classified all cases into the following prognostic categories according to different TNM stages: early stage group (T1-2N0-1M0), advanced local disease group (T3-4N0-1M0), advanced nodal disease group (T1-2N2-3M0), and advanced locoregional disease group (T3-4N2-3M0). The 5-year overall survival (OS), local relapse-free survival (LRFS), and distant metastases-free survival (DMFS) were 83.0%, 90.4%, and 84.0%, respectively. The early disease group had the lowest treatment failure rate, with a 5-year OS of 95.6%. The advanced local disease group and advanced nodal disease group had similar failure pattern and treatment outcomes as well as similar hazard ratios for death (4.230 and 4.625, respectively). The advanced locoregional disease group had the highest incidence of relapse and death, with a 5-year DMFS and OS of 62.3% and 62.2%, respectively, and a hazard ratio for death of 10.402. Comparing with IMRT alone, IMRT in combination with chemotherapy provided no significant benefit to locoregionally advanced NPC. Our results suggest that the decision of treatment strategy for NPC patients should consider combinations of T and N stages, and that IMRT alone for early stage NPC patients can produce satisfactory results. However, for advanced local, nodal, and locoregional disease groups, a combination of chemotherapy and radiotherapy is recommended.

Clinical features of 337 patients with recurrent nasopharyngeal carcinoma / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>At present, although appropriate radiotherapy and combined treatments are widely used for the patients with primary nasopharyngeal carcinoma (NPC), local or regional recurrence rates are still high. According to clinical performance, pathology, and diagnostic imaging of the patients with the first recurrence of NPC, this study analyzed the clinical features of recurrent NPC to provide a reference for tracking the rules of recurrence after the treatment of patients with NPC.</p><p><b>METHODS</b>Clinical data of 337 patients diagnosed with recurrent NPC for the first time were collected. The diagnoses were based on pathology and/or imaging and the patients were treated at the Sun Yat-sen University Cancer Center between January 1999 and December 2004. Data used for statistical analysis included clinical performance during the patient visit, the extension of the invasion as shown on imaging, pathologic features, Epstein-Barr virus (EBV) serology, restaging, etc.</p><p><b>RESULTS</b>Patients were staged according to the system developed by the International Union Against Cancer (UICC) and the American Joint Committee on Cancer (AJCC) in 2002. Patients with diseases at stages I/II accounted for 25.2%, while those with stage III/IV accounted for 74.8%. The median interval of relapse was 25 months. Patients had local recurrence (69.4%), regional recurrence (4.5%), or both (26.1%). Epistaxis and headache were the most common symptoms. Abduct dysfunction and facial numbness induced by cranial nerve damage were the most common signs. The probability of invasion of structures adjacent to the nasopharynx, such as the oropharynx, the prestyloid space, and the carotid sheath area, was low in patients with recurrent NPC. By contrast, the probability of invasion of structures far from the nasopharynx, such as the base of the skull, the paranasal sinuses, cranial nerves, the cavernous sinus, the brain, the pterygopalatine fossa, the infratemporal fossa, the orbital apex, and the soft palate, was higher in recurrent NPC.</p><p><b>CONCLUSIONS</b>The most common interval of relapse is about 2 years. The relapsed disease is usually more widespread and located deeper. Most recurrent NPC is advanced disease.</p>

Time course of let-7a expression in the cell cycle of human cervical carcinoma HeLa cells / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the time course of let-7a microRNA expression in the cell cycle of HeLa cells.</p><p><b>METHODS</b>HeLa cells were synchronized in G(1), S and G(2)/M phases using double-thymidine block, and the cell cycle phases were defined by flow cytometry. Real-time quantitative RT-PCR was used to examine the expression of let-7a in HeLa cells in different cell cycle phases.</p><p><b>RESULTS</b>The synchronization rates of G(1), S and G(2)/M phases were 84.81%, 83.65% and 77.69%, respectively. Let-7a was constitutively expressed throughout the cell cycle in HeLa cells, but the expression levels in G(1) and S phases were lower than those in G(2)/M phase.</p><p><b>CONCLUSIONS</b>Cell cycle can significantly influence the expression level of let-7a, which may provide new clues to the understanding of the cell cycle control mechanisms.</p>