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.

Analysis of Changes in Failure Risk Over Time of Patients with Locoregionally Advanced Nasopharyngeal Carcinoma / 中山大学学报(医学科学版)

[Objective] This study aims to investigate the changes in risk of disease failure in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) after treatment over time and provide reference for individualized follow-up.[Methods] 556 patients receiving intensity-modulated radiotherapy (IMRT) from 2009 to 2010 were analyzed.The failure free survival (FFS) and annual hazard rates of disease failure were estimated using the life-table method.We also used the difference confidence interval to evaluate the difference between different failure risk rates.[Results] The median follow-up in study was 83 months.A total of 119 patients experienced the treatment failure during the follow-up period.The 5-year failure-free survival rate of the whole cohort was 80.6％ and the curve of failure risk showed an increase in the first two years and a slow decline after two years.The comparison of the rates of failure risk in different stages between the peak year and the subsequent years were as follow:For patients with stage Ⅲ,failure risk rate of the second year was significantly 3.2％ higher than that in the fifth year;Rate of the second year was significantly 18.4％ higher than that in the fourth year for patients with stage ⅣB.No significantly difference was found in other results.Additionally,the risks of failure in patients with ⅣB were significantly higher than that in patients with stage Ⅲ in the first two years and in patients with stage ⅣA in the second year.[Conclusion] The curve of failure risk for patients with locoregionally advanced NPC reached a relative peak in the second year.It is recommended that patients with stage Ⅲ maintain a relatively high follow-up frequency within 3-4 years after treatment;Patients in stage ⅣA were not recommended to reduce the frequency of follow-up within 3-5 years;It was recommended that the frequency of follow-up could not be reduced within 2-3 years,and should be given a more intensive follow-up strategy than patients with stage Ⅲ-ⅣA in the first two years.

Subdivision of M category for nasopharyngeal carcinoma with synchronous metastasis: time to expand the M categorization system / 癌症

<p><b>INTRODUCTION</b>The current metastatic category (M) of nasopharyngeal carcinoma (NPC) is a "catch-all" classification, covering a heterogeneous group of tumors ranging from potentially curable to incurable. The aim of this study was to design an M categorization system that could be applied in planning the treatment of NPC with synchronous metastasis.</p><p><b>METHODS</b>A total of 505 NPC patients diagnosed with synchronous metastasis at Sun Yat-sen University Cancer Center between 2000 and 2009 were involved. The associations of clinical variables, metastatic features, and a proposed M categorization system with overall survival (OS) were determined by using Cox regression model.</p><p><b>RESULTS</b>Multivariate analysis showed that Union for International Cancer Control (UICC) N category (N1-3/N0), number of metastatic lesions (multiple/single), liver involvement (yes/no), radiotherapy to primary tumor (yes/no), and cycles of chemotherapy (>4/≤4) were independent prognostic factors for OS. We defined the following subcategories based on liver involvement and the number of metastatic lesions: M1a, single lesion confined to an isolated organ or location except the liver; M1b, single lesion in the liver and/or multiple lesions in any organs or locations except the liver; and M1c, multiple lesions in the liver. Of the 505 cases, 74 (14.7%) were classified as M1a, 296 (58.6%) as M1b, 134 (26.5%) as M1c, and 1 was not specified. The three M1 subcategories showed significant difference in OS [M1b vs. M1a, hazard ratio (HR) = 1.69, 95% confidence interval (CI) = 1.16-2.48, P = 0.007; M1c vs. M1a, HR = 2.64, 95% CI = 1.75-3.98, P < 0.001].</p><p><b>CONCLUSIONS</b>We developed an M categorization system based on the independent factors related to the prognosis of patients with metastatic NPC. This system may be helpful to further optimize individualized care for NPC patients.</p>

The clinical characteristics and treatment outcome of 57 children and adolescents with primary central nervous system germ cell tumors / 癌症

Primary central nervous system germ cell tumors (CNS-GCTs) in children and adolescents have unique clinical features and methods of treatment compared with those in adults. There is little information about Chinese children and adolescents with CNS-GCTs. Therefore, in this study we retrospectively analyzed the clinical features and treatment outcome of Chinese children and adolescents with primary CNS-GCTs. Between January 2002 and December 2012, 57 untreated patients from a single institution were enrolled. They were diagnosed with CNS-GCTs after pathologic or clinical assessment. Of the 57 patients, 41 were males and 16 were females, with a median age of 12.8 years (range, 2.7 to 18.0 years) at diagnosis; 43 (75.4%) had non-germinomatous germ cell tumors (NGGCTs) and 14 (24.6%) had germinomas; 44 (77.2%) had localized disease and 13 (22.8%) had extensive lesions. Fifty-three patients completed the prescribed treatment, of which 18 underwent monotherapy of surgery, radiotherapy, or chemotherapy, and 35 underwent multimodality therapies that included radiotherapy combined with chemotherapy or surgery combined with chemotherapy and/or radiotherapy. PEB (cisplatin, etoposide, and bleomycin) protocol was the major chemotherapy regimen. The median follow-up time was 32.3 months (range, 1.2 to 139 months). Fourteen patients died of relapse or disease progression. The 3-year event-free survival (EFS) and overall survival rates for all patients were 72.2% and 73.8%, respectively. The 3-year EFS was 92.9% for germinomas and 64.8% for NGGCTs (P = 0.064). The 3-year EFS rates for patients with NGGCTs who underwent monotherapy and multimodality therapies were 50.6% and 73.5%, respectively (P = 0.042). Our results indicate that multimodality therapies including chemotherapy plus radiotherapy were better treatment option for children and adolescents with CNS-GCTs.

Evaluation of the prognostic significance of refinement and stratification of distant metastasis status in 1016 cases of nasopharyngeal carcinoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the prognostic factors for nasopharyngeal carcinoma (NPC) with different metastatic status, and to improve the NPC management by multi-level refinement and stratification of M1 stage distant metastases.</p><p><b>METHODS</b>Clinicopathological data of 1016 NPC patients with distant metastases were retrospectively reviewed. The M1 stage distant metastases were subdivided into synchronous or metachronous metastases, metastatic sites (lung, bone, liver), number of metastatic organs (solitary, multiple) and number of metastases (solitary, multiple) subgroups to analyze the prognosis and survival of the patients.</p><p><b>RESULTS</b>The most frequently involved metastatic sites were bone (542, 53.3%), lung (420, 41.3%) and liver (302, 29.7%). There were solitary metastatic lesions in 164 patients (16.2%), synchronous metastases in 376 cases and metachronous metastases in 640 cases. The median overall survival of the whole group of 1016 NPC patients was 30.8 months since the time of diagnosis of metastasis. For the 376 patients in the synchronous metastasis group, the median survival was 23.3 months and the 1-, 3- and 5-year overall survival rates were 74.2%, 27.6% and 18.5%, respectively. For the 640 patients in the metachronous metastases group, the median survival was 36.7 months, and the 1-, 3- and 5-year overall survival rates were 88.1%, 49.6% and 28.6%, respectively, with a significant difference between the two groups (all P < 0.001). Cox multivariate analysis indicated that the number of metastatic lesions, different metastatic sites and N stage at initial diagnosis were independent prognostic factors for patients with metachronous metastases (P < 0.05).</p><p><b>CONCLUSIONS</b>A theory of detailed multi-level metastasis (M1) stratification aiming at different distant metastasis status for nasopharyngeal carcinoma is proposed. To take appropriate individualized treatment scheme according to the prognosis and expected survival should be helpful to improving the diagnosis and treatment of nasopharyngeal cancer.</p>

Histone deacetylase inhibitor, 2-propylpentanoic acid, increases the chemosensitivity and radiosensitivity of human glioma cell lines in vitro / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Treatment for malignant glioma generally consists of cytoreductive surgery followed by radiotherapy and chemotherapy. In this study, we intended to investigate the effects of 2-propylpentanoic acid (VPA), a histone deacetylase inhibitor, on chemosensitivity and radiosensitivity in human glioma cell lines.</p><p><b>METHODS</b>Human glioma cell lines, T98-G, and SF295, were treated with temozolomide (TMZ) or irradiation (IR), with or without VPA (1.0 mmol/L). Then, cytotoxicity and clonogenic survival assay was performed. Cell cycle stage, apoptosis, and autophagy were also detected using flow cytometry and dansyl monocadaverin (MDC) incorporation assay. One-way analysis of variance (ANOVA) and t-test were used to analyze the differences among variant groups.</p><p><b>RESULTS</b>Mild cytotoxicity of VPA was revealed in both cell lines, T98-G and SF295, with the 50% inhibiting concentration (IC50) value of (3.85 ± 0.58) mmol/L and (2.15 ± 0.38) mmol/L, respectively; while the IC50 value of TMZ was (0.20 ± 0.09) mmol/L for T98-G and (0.08 ± 0.02) mmol/L for SF295. Moreover, if combined with VPA (1.0 mmol/L) for 96 hours, the sensitivity of glioma cells to TMZ was significant increased (P < 0.05). The surviving fractions at 2 Gy (SF2) of T98-G and SF295 cells exposed to IR alone were 0.52 and 0.58. However, when VPA was combined with IR, the SF2 of T98-G and SF295 dropped to 0.39 (P = 0.047) and 0.49 (P = 0.049), respectively. Treatment with VPA plus TMZ or IR also resulted in a significant decrease in the proportion of cells in the G2 phase and increased apoptotic rates as well as autophagy in T98-G and SF295 cell lines (P < 0.01).</p><p><b>CONCLUSION</b>VPA may enhance the activities of TMZ and IR on glioma cells possibly through cell cycle block and promote autophagy, and thus could be a potential sensitizer of glioma treatment.</p>

Establishment and characterization of a novel nasopharyngeal carcinoma cell line (SUNE2) from a Cantonese patient / 癌症

The undifferentiated form of nasopharyngeal carcinoma (NPC) is the most common malignant head and neck cancer in South China, especially in Cantonese populations. However, few NPC cell lines have been established from the patients in this region. In this study, we established a new NPC cell line, termed SUNE2, from a Cantonese patient with undifferentiated NPC. This cell line had extremely low concentrations of Epstein-Barr virus (EBV) DNA in long-term culture and expressed low levels of latent membrane protein 1 (LMP1), latent membrane protein 2A (LMP2A), BamH1-A right frame 1 (BARF1), EBV-encoded RNA-1 (EBER1), and EBV-encoded RNA-2 (EBER2) in early passages. SUNE2 cells also showed much stronger transforming ability than 5-8F cells in colony formation assays and anchorage-independent growth assays in soft agar, and they only need 2 weeks to form tumors in nude mice. In summary, the SUNE2 cell line is a new in vitro model that can be used for further research on the mechanisms underlying the occurrence and development of NPC.

Increased pretreatment levels of serum LDH and ALP as poor prognostic factors for nasopharyngeal carcinoma / 癌症

Serum enzymes that play potential roles in tumor growth have recently been reported to have prognostic relevance in a diverse array of tumors. However, prognosis-related serum enzymes are rarely reported for nasopharyngeal carcinoma(NPC). To clarify whether the level of serum enzymes is linked to the prognosis of NPC, we reviewed the pretreatment data of lactate dehydrogenase(LDH), alkaline phosphatase (ALP), and glutamyl transferase (GGT) in 533 newly diagnosed NPC patients who underwent radical radiotherapy between May 2002 and October 2003 at Sun Yat-sen University Cancer Center. Patients were grouped according to the upper limit of normal values of LDH, ALP, and GGT. The Kaplan-Meier method and log-rank test were used for selecting prognostic factors from clinical characteristics and serum enzymes, and the chi-square test was applied to analyze the relationships of clinical characteristics and serum enzymes. Finally, a Cox proportional hazards model was used to identify the independent prognostic factors. We found that increased levels of LDH had poor effects on both overall survival and distant metastasis-free survival (P = 0.009 and 0.035, respectively), and increased pretreatment level of serum ALP had poor effects on both overall survival and local recurrence-free survival (P = 0.037 and 0.039, respectively). In multivariate analysis, increased LDH level was identified as an independent prognostic factor for overall survival. Therefore, we conclude that increased pretreatment serum LDH and ALP levels are poor prognostic factors for NPC.

Long-term molecular changes in WHO grade II astrocytomas following radiotherapy / 癌症

Monitoring the long-term radiotherapy-associated molecular changes in low-grade gliomas (LGGs) facilitates the understanding of LGG response to radiotherapy. In this study, we used immunohistochemistry to analyze the expression of Ki-67, tumor protein P53 (TP53), P21, and P27 in 8 paired WHO grade II astrocytoma samples. The interval between radiotherapy (RT) and the second surgery was more than 3 months in all cases. The average Ki-67 labeling index (LI) was 5.3% in pre-RT samples and 11.54% in post-RT samples. Ki-67 LI was higher in the primary tumors that underwent malignant transformation observed at the second surgery after radiation. Post-RT Ki-67 LI decreased in 2 cases with an interval of less than 12 months between RT and the second surgery. TP53 expression was found in 3 out of 4 pre-RT samples with malignant transformation and in 1 out of 4 pre-RT samples without malignant transformation. Post-RT TP53 increased in 2 cases in which increased expression of P21 or P27 was also observed. Our study suggests that radiotherapy can inhibit WHO grade II astrocytoma proliferation as reflected by Ki-67 LI, but the effect attenuates with time. In addition, there is a tendency of malignant transformation for WHO grade II astrocytomas with a high Ki-67 level or TP53 expression in initial samples.

Establishment of a specific serum proteomic profile model of nasopharyngeal carcinoma by MALDI-TOF MS / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To determine the specific serum peptide profile by comparing the serum differences between nasopharyngeal carcinoma patients (NPC) and normal control subjects, and to provide a diagnostic model of nasopharyngeal carcinoma.</p><p><b>METHODS</b>Pre-treatment serum samples of NPC and normal control subjects were collected and assayed by MALDI-TOF MS analysis. The peptides were extracted with magnetic beads coated with WCX. Mass spectrographic data were analyzed with ClinProt(TM) software. The specific serum peptide model of NPC was established by using genetic algorithms. The sensitivity and specificity of model were tested by blind testing.</p><p><b>RESULTS</b>The serum peptidome patterns of nasopharyngeal carcinoma was obtained. Differential expression of 99 peptide peaks was deteced, and the 808.99 Da, 834.61 Da, 3954.82 Da, 8141.88 Da peptide peaks showing statistically significant differences between the two groups, were used to establish the diagnostic model for nasopharyngeal cancer. The recognition rate and predictive power of the model were 90.0% and 84.3%, respectively. The sensitivity and specificity of the model were 80.0% and 64.0% determined by blind testing, respectively.</p><p><b>CONCLUSIONS</b>Significant differences of serum peptide peaks are detected between NPC and normal control groups. The established specific serum peptide model may have certain application in the diagnosis of nasopharyngeal carcinoma, and provides the basis for discovering specific tumor markers of nasopharyngeal carcinoma.</p>

Relationship between traditional Chinese medicine syndrome differentiation and imaging characterization to the radiosensitivity of nasopharyngeal carcinoma / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Traditional Chinese medicine (TCM) is a well established and time-honored practice in China, employing syndrome differentiation as a basis for the treatment of disease. According to different TCM syndrome typing findings, combining modern medical methods with TCM approaches can improve the quality of life and comprehensive effect on patients with nasopharyngeal carcinoma (NPC). This study investigated the relationship between TCM syndrome typing and imaging characterization to radiosensitivity as to provide objective evidence for the integration of Chinese and modern medical approaches in the treatment of NPC.</p><p><b>METHODS</b>Prior to treatment, TCM syndrome typing, computed tomography (CT) and magnetic resonance imaging (MRI) were performed on 147 patients pathologically classified with NPC. The status of tumor remission was radiologically evaluated at accumulated doses of 20 Gy, 40 Gy and 60 Gy, and at 3 months after completion of radiotherapy. Statistical results were analyzed by the Friedman and K-W test procedures.</p><p><b>RESULTS</b>Prior to treatment, TCM syndrome typing of NPC included Lung Heat, Blood Stasis, Phlegm Congealment and Blood Stasis-Phlegm Congealment. Lung Heat typing accounted for the highest proportion at 34.7% (51/147), followed by Phlegm Congealment at 32.7% (48/147), Blood Stasis at 17.0% (25/147) and Blood Stasis-Phlegm Congealment at 15.7% (23/147). Radiological imaging demonstrated a higher incidence of cervical lymph node metastases in Phlegm Congealment and Blood Stasis-Phlegm Congealment types (P<0.05), while Blood Stasis and Blood Stasis-Phlegm Congealment types were more prone to skull base invasion (P<0.05). Residual tumor size was larger in Blood Stasis and Blood Stasis-Phlegm Congealment types than in Lung Heat and Phlegm Congealment types after 3 months of treatment (P<0.05).</p><p><b>CONCLUSIONS</b>Different radiological manifestations were observed in TCM syndrome typed NPC patients, with lesser radiosensitivity demonstrated in the Blood Stasis and the Blood Stasis-Phlegm Congealment types relative to the Lung Heat and Phlegm Congealment types.</p>

Influence of level-Ib lymphadenopathy on the prognosis of nasopharyngeal carcinoma / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>The level-Ib lymph node metastasis is rare in nasopharyngeal carcinoma (NPC). When and how this level should be irradiated with precise radiotherapy remains controversial. This study evaluated the prevalence and prognostic significance of level-Ib lymphadenopathy on the prognosis of NPC patients.</p><p><b>METHODS</b>From January 1990 and December 1999, 933 newly diagnosed patients with NPC treated at Sun Yat-sen University Cancer Center were randomly selected, examined with computed tomography (CT) imagining for evidence of level-Ib lymphadenopathy before treatment. All patients received radical radiotherapy with or without chemotherapy. The relationship between level-Ib lymphadenopathy and post-treatment outcomes including overall survival (OS), locoregional recurrence-free survival (LRFS), and distant metastasis-free survival (DMFS) were analyzed using Kaplan-Meier methods. The Cox proportional hazards regression model was used to adjust for other prognostic factors.</p><p><b>RESULTS</b>Of the 933 patients, 55 (5.9%) were found to have level-Ib lymphadenopathy, which was associated with carotid sheath involvement, oropharynx involvement and levels, and lateral cervical lymph node involvement. In the subgroup with carotid sheath involvement, with multivariate analysis accounting for all previously known prognostic factors, level-Ib lymphadenopathy was still associated with a risk of decreased OS (RR, 2.124; P<0.001), DMFS (RR, 2.168; P<0.001), and LRFS (RR, 1.989; P=0.001).</p><p><b>CONCLUSION</b>Level-Ib lymphadenopathy in the patients with carotid sheath involvement is an independent prognostic factor.</p>

Continuous fall in hemoglobin level is a poor prognostic factor in patients with nasopharyngeal carcinoma treated with radiotherapy / 癌症

<p><b>BACKGROUND AND OBJECTIVE</b>Anemia can not only reduce the quality of life of patients with cancer, but also affect their survival. This study was to investigate the prognostic value of hemoglobin (Hb) level in patients with nasopharyngeal carcinoma (NPC) treated with radiotherapy.</p><p><b>METHODS</b>Clinical data of 520 NPC patients received definitive radiotherapy between 2000 and 2002 at Sun Yat sen University Cancer Center were analyzed. Patients were stratified into normal Hb level and anemia groups according to their Hb levels before, during, and after radiation. Anemia was defined according to World Health Organization criteria as Hb level < 130 g/L in men and < 120 g/L in women. Hb continuous decrease group and non decrease group were defined according to Hb changes in the patients during radiotherapy. Loco regional recurrence free survival (LRFS) and overall survival (OS) rates were estimated using the Kaplan Meier method. Multivariate analysis was performed using the Cox model to analyze the prognostic factors.</p><p><b>RESULTS</b>Before radiation, the 5 year LRFS rates were 60.9% in anemia group and 63.9% in normal Hb level group (P = 0.337); the 5 year OS rates were 65.2% and 71.0%, respectively (P = 0.299). During radiation, the 5 year LRFS rates were 56.7% in anemia group and 67.9% in normal Hb level group (P = 0.013); the 5 year OS rates were 61.0% and 75.9%, respectively (P = 0.001). After radiation, the 5 year LRFS rates were 59.6% in anemia group and 64.9% in normal Hb level group (P = 0.169); the 5 year OS rates were 65.0% and 71.9%, respectively (P = 0.090). The 5 year LRFS and OS rates were significantly lower in Hb continuous decrease group than in Hb non decrease group (59.1% vs. 69.3%, P = 0.032; 66.2% vs. 76.4%, P=0.011). Multivariate analysis showed that the continuous decrease of Hb was an independent prognostic factor for OS.</p><p><b>CONCLUSION</b>The change in Hb level during radiotherapy is an important prognostic factor affecting the OS of NPC patients.</p>

DNA-dependent protein kinase activity and radiosensitivity of nasopharyngeal carcinoma cell lines CNE1/CNE2 / 生理学报

The present study investigated the relationship between DNA-dependent protein kinase (DNA-PK) and radiosensitivity of nasopharyngeal carcinoma (NPC) cell lines. The dose-survival relationship for NPC cell lines, CNE1 and CNE2, was analyzed using clonogenic formation assay, the activity of DNA-PK of the two cell lines was measured using the Signa TECT DNA-PK assay kit, and the localization and expression of Kus (a heterodimer) and DNA-PKcs protein in CNE1 and CNE2 before irradiation and 15 min, 1 h, 6 h, 12 h, 24 h after 4 Gy irradiation were analyzed by immunofluorescence, laser scanning confocal microscope (LSCM) and Western blot. The results showed that the surviving fraction of CNE1 was higher than that of CNE2 at each dose. The DNA-PK activity of CNE1 was also significantly higher than that of CNE2 before and after irradiation (P<0.05), while the expression of total Ku70/Ku80 in CNE1 and CNE2 had no significant difference. Increasing translocation of Ku70 and Ku80 from the cytoplasm to the nuclei in the two cell lines was observed with increase of irradiation time as detected by Western blot, and the immunofluorescence of the DNA-PK complex subunits showed greater nuclear translocation in CNE1 than CNE2 after irradiation. The results suggest that the relatively higher radio-resistance of CNE1 correlates with the higher activity of DNA-PK as compared to that of more radiosensitive CNE2 (or lower radio-resistance) before and after irradiation. Thus, DNA-PK activity may be a useful predictor of radiosensitivity of NPC.

Correlation of DNA-PK activity with anti-cancer drug-sensitivity in human gliomas / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the relationship between DNA-dependent protein kinase (DNA-PK) activity and anti-cancer drug sensitivity in human glioma tissues.</p><p><b>METHODS</b>Human glioma specimens were primarily cultured and its sensitivity to several anti-cancer drugs were evaluated by MTT assay. Nuclear protein was extracted from the glioma sample of the same patient and its DNA-PK activity was determined by a biotinylated DNA-PK assay with p53-derived peptide as a specific substrate.</p><p><b>RESULTS</b>DNA-PK activity varied widely among these glioma samples. Of all 36 samples, 16 showed higher DNA-PK activity (relative activity > or = 0.40) and 20 samples with lower DNA-PK activity (relative activity < 0.40). The gliomas sensitive to DDP and VCR as evaluated by inhibition rate (IR > or = 50%) under plasma peak concentration (PPC) showed lower DNA-PK activity than the resistant ones (IR < 50%) (t = -3.445, P < 0.01). Furthermore, the gliomas with higher DNA-PK activity showed lower inhibition rate (IR < 50%) than those with lower DNA-PK activity ones (t = -2.145, P < 0.05).</p><p><b>CONCLUSION</b>DNA-PK activity is significantly associated with anti-cancer drug sensitivity to DDP and VCR in human gliomas. DNA-PK activity could be used as a new biomarker for the chemotherapy sensitivity of human gliomas.</p>

Treatment outcome and prognosis of 112 patients with nasal and nasopharyngeal peripheral T cell lymphomas / 中华血液学杂志

<p><b>OBJECTIVE</b>To retrospectively analyze the treatment outcomes and prognostic factors of nasal and nasopharyngeal peripheral T cell lymphomas (PTCL) patients.</p><p><b>METHODS</b>One hundred and twelve patients with pathologically confirmed nasal and nasopharyngeal PTCL were included, among which 39 were CD56(+) NK/T cell lymphomas. The median pre-treatment disease course was 4 months. 84 were males and 28 females median age was 46 years. The tumors mainly involved nasal cavity (88 cases) and/or nasopharynx (50 cases) and adjacent structures, and 83 cases with extra-cavity diseases. 91.1% of the patients had Ann Arbor I(E)/II(E) diseases. The International Prognostic Indices (IPI) were less than 2 scores in 78.8% of the patients. Seventy two patients received combined chemo-radiotherapy, 32 chemotherapy only, 3 radiotherapy only and 5 no any treatment.</p><p><b>RESULTS</b>Median follow-up duration was 42 months. Chemotherapy achieved a complete remission (CR) rate of 34.4% for initial treatment, and of 65.1% after primary treatment. The local tumor controlled rate was 50.5%, and the median time to tumor progression (TTP) was 11 months. There were evidences of systemic relapse in more than 30% of the patients. The extra-cavity tumors usually had a shorter TTP (r(s) = -0.191, P = 0.024). The progress-free survival and overall survival rates were 38.8% and 52.4% at 3 years, and 34.9% and 44.8% at 5 years respectively. Univariate analysis showed that favorable prognostic factors for survival were pre-treatment course > 3 months, earlier clinical stage, non NK/T lymphoma, no skin involvement, lower IPI, CR after initial chemotherapy, radiotherapy, CR after primary treatment and local tumor controlled. Multivariate analysis showed that, pre-treatment course > 3 months (P = 0.011), non NK/T lymphoma (P = 0.007), CR after initial chemotherapy (P = 0.008) and radiotherapy (P = 0.000) were favorable prognostic factors for survival.</p><p><b>CONCLUSIONS</b>Although most nasal and nasopharyngeal peripheral T-cell lymphomas were diagnosed at early stage diseases, some of them were highly aggressive with poor prognosis, particularly CD56(+) NK/T cell lymphomas. Combination chemo/radiotherapy, though remained principal treatments, more effective therapeutic modalities are expected.</p>

Clinical features and prognosis of nasal type NK/T cell lymphoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the clinical features, treatment modalities and the prognosis of nasal type NK/T cell lymphoma.</p><p><b>METHODS</b>The data of 39 such patients treated from June 2000 to December 2003 were retrospectively reviewed. Twenty three patients were treated by combined chemoradiotherapy, basing on anthracycline-containing CHOP or similar regimens (median 5 cycles). Eleven patients by chemotherapy alone, 2 by radiotherapy alone and 2 aged patients by palliative chemotherapy or radiotherapy. Radiotherapy was given by high energy photon ray combined with electron beam with a median curative dose of 56 Gy in conventional fractionation. Bivariate correlations and univariate prognostic factors were analyzed.</p><p><b>RESULTS</b>Median follow-up time for the 21 patients who were still alive was 22.5 months. The overall remission rate (RR) after initial treatment was 66.7% (21 CR, 3 PR). Chemotherapy alone got a CR rate of only 37.5%. The overall local control rate was 59.4%. Local relapse rate after curative radiotherapy was 25.0%. Radiotherapy was positively correlated with local control (P = 0.000) and time to disease progression (TTP, P = 0.002). Skin and intestine were among the extranodal relapse sites. Fifteen patients had highly aggressive tumors with a median survival time of only 5 months. Univariate analysis showed that significant favorable survival prognostic factors were: radiotherapy (P = 0.001); lower risk International Prognostic Index (IPI, P = 0.001); complete remission after primary treatment (P = 0.000); pre-diagnostic history > 2 months (P = 0.024); and free of skin involvement (P = 0.034).</p><p><b>CONCLUSION</b>Most of nasal type NK/T cell lymphoma are in early stage when diagnosed. Radiotherapy remains to be the mainstay of treatment. Combined chemoradiotherapy needs further improvement for the progressive disease type. Some patients may have highly aggressive tumors with poor prognosis. Optimal prognostic factors and individualized treatment regimens need to be investigated.</p>

Retrospective analysis of 934 nasopharyngeal carcinoma patients treated with conventional external beam radiotherapy alone / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To analyze the clinical outcome of 934 primary nasopharyngeal carcinoma treated with conventional external beam radiotherapy alone.</p><p><b>METHODS</b>34 patients were treated from Jan. 1, 1999 to Dec. 31, 1999. The radiation fields were delineated according to the CT/MRI imaging findings on disease extent. Two lateral opposing isocentric portals with customized blockings were used for the nasopharynx and upper neck. The dose delivered to tumor in the nasopharynx was 68-70 Gy/2 Gy fraction/7 weeks. The doses delivered to the neck was 60-70 Gy/6-7 weeks for patients with positive lymph nodes and 50 Gy/5 weeks for the patients with negative lymph node.</p><p><b>RESULTS</b>The 1-, 2-, 3- and 4-year overall survival rate (OS) was 89.5%, 81.9%, 78.1% and 75.7%, and metastasis-free survival rate (MFS) was 84.0%, 77.2%, 74.4% and 72.0%, respectively. The 1-, 2-, 3- and 4-year disease-free survival rate (DFS) was 80.8%, 73.1%, 68.5% and 65.1%, and the relapse-free survival rate (RFS) was 95.5%, 92.7%, 90.3% and 87.3%, respectively. The overall failure rate was 30.9% (289/934). At the end of the radiotherapeutic course, the percentage of residual disease was 14.6%. The 4-year loco-regional recurrence and distant metastasis rates after radiotherapy were 7.2% and 9.2% with a median time of 19.3 months and 12.8 months.</p><p><b>CONCLUSION</b>It may be helpful to improve radiotherapy curative effect when the target is individually designed through improving irradiation technique according to CT/MRI findings and by shortening the overall course time, enhancing irradiation dose and strictly implementing QA/QC measures.</p>