Impact of HLA-E gene polymorphism on HLA-E expression in tumor cells and prognosis in patients with stage III colorectal cancer.

Human leukocyte antigen (HLA)-E can contribute to the escape of cancer cells from host immune mechanisms. However, it is unknown whether HLA-E gene polymorphisms might play a role in cancer immune escape. This study aimed to evaluate the correlation between HLA-E gene polymorphisms and HLA-E expression in tumor tissue and determine the effects on clinical outcome of patients with stage III colorectal cancer. Two hundred thirty patients with stage III colorectal cancer were enrolled. HLA-E expression was detected in patient-derived tumor tissues with immunohistochemistry. HLA-E gene alleles in tumor tissues were detected with the polymerase chain reaction-sequence-specific primer method. In colorectal cancer tissue and in the normal tissue adjacent to the tumor, the HLA-E expression rates were 72.2 and 15.1 %, respectively (P < 0.05). Patients with overexpression, low expression, and no expression of HLA-E exhibited disease-free survival of 55.3, 72.9, and 72.1 %, respectively. Patients with HLA-E overexpression exhibited the lowest long-term survival rate. No relationship was observed between the type of HLA-E gene polymorphism and its expression level in tumor tissues; moreover, no polymorphisms appeared to affect the long-term survival of patients with colorectal cancer. The type of HLA-E polymorphism did not have an impact on HLA-E expression in tumors or the prognosis in patients with stage III colorectal cancer. However, the level of HLA-E expression in tumor tissue strongly predicted long-term survival in these patients.

[Efficacy of modified B-NHL-BFM-90 protocol on anaplastic T-cell lymphoma in children and adolescents].

BACKGROUND AND OBJECTIVE: Anaplastic T-cell lymphoma in children and adolescents is an aggressive malignant non-Hodgkin's lymphoma (NHL). The optimal treatment regimen needs to be investigated. This study was to evaluate the efficacy of modified B-NHL-BFM-90 protocol on anaplastic T-cell lymphoma in children and adolescents. METHODS: From October 2002 to January 2008, 18 untreated anaplastic T-cell lymphoma patients aged less than 16 years were enrolled, and treated with modified B-NHL-BFM-90 protocol including cyclophosphamide, vincristine, ifosfamide, etoposide, adriamycin, HD-methotrexate, vindesine, dexamethasone, cytarabine/HD-cytarabine. Intrathecal injection was given every course. RESULTS: Of the 18 patients, 15 (83.3%) achieved complete remission (CR), and three (16.7%) achieved partial remission (PR). The patients were followed up for 4-68 months (median, 31 months). The 3-year event-free survival (EFS) rates were (87.4+/-8.4)% for all patients, 100% for stage II patients, and (85.1+/-9.7)% for stage III/IV patients; 100% for low risk group, (88.9+/-10.5)% for moderate risk group, and (80.0+/-17.9)% for high risk group. Most patients suffered from grade 3-4 myelosuppression and recovered after active support care. One patient with stage IV disease received autologous peripheral blood stem cell transplantation (PBSCT) after CR and was still alive. Two patients had tumor relapsed and died at three and five months after off treatment, respectively. CONCLUSIONS: Modified B-NHL-BFM-90 protocol, with tolerable toxicity, is an effective treatment regimen for anaplastic T-cell lymphoma in children and adolescents. It should be used in experienced cancer centers and hematological units.

[Clinical characteristics and prognosis of different subtypes of breast cancer].

OBJECTIVE: To investigate the clinical characteristics and prognosis of patients with different subtypes of breast cancer: basaloid, HER-2 and luminal types, and try to find the evidence of individualized treatment for the patients. METHODS: 1280 histologically and immunohistochemically proven patients with resectable breast cancer were treated, and the clinical data including characteristics, relapse and survival of the patients with different subtypes of breast cancer were analyzed retrospectively. RESULTS: Of the 1280 breast cancer patients, basaloid, HER-2 and luminal types accounted for 20.9%, 23.2% and 55.9%, respectively. Basaloid type was more likely to be found in younger patients frequently with a family history of breast cancer. HER-2 type usually had a tumor of larger size with more advanced stage disease and more metastatic lymph nodes. Luminal type was likely to occur in aged patients with an earlier stage disease. The recurrence rates in basaloid, HER-2 and luminal types were 25.0%, 27.9% and 11.7%, respectively. Patients with basaloid or HER-2 type were found to have a significantly higher recurrence rate than the patients with luminal type breast cancer (P < 0.001), but no significant difference was observed between the basaloid and HER-2 types. However, patients with basaloid type breast cancer were more likely to develop lung metastasis than HER-2 type (13.4% vs. 7.1%, P = 0.017). Up to December 2006, the 5-year disease-free survival (DFS) rates for patients with basaloid, HER-2 and luminal types were 72.2%, 68.2% and 86.2% (P < 0.001), respectively. The overall 5-yr survival (OS) rates of the three groups were 88.6%, 83.8% and 95.8% (P < 0.001) , respectively. Of the patients with luminal type breast cancer, HER2-negative patients had a higher DFS (86.2% vs 57.0%, P < 0.001) and OS (95.8% vs 87.7%, P = 0.0001) compared with those with HER2-positive. The results of Multivariate Cox Regression showed that tumor size and lymph node state were the most important factors influencing the prognosis. CONCLUSION: Each subtype of breast cancer has somewhat its own specific clinical features in terms of recurrence pattern and prognosis, therefore, individualized treatment regimen may be required.

Intensive chemotherapy improved treatment outcome for Chinese children and adolescents with lymphoblastic lymphoma.

BACKGROUND: Lymphoblastic lymphoma (LBL) is a highly aggressive lymphoma, for which intensive chemotherapy is necessary. This study was designed to evaluate the efficacy and toxicity of a modified acute lymphoblastic leukemia (ALL)-Berlin-Frankfurt-Münster (BFM)-90-based protocol in Chinese children and adolescents with LBL. METHODS: From March 1998 to November 2006, 60 untreated patients with LBL (age <18 years) from a single institution were enrolled. All patients were treated with the modified ALL-BFM-90 protocol, and prophylactic cranial radiotherapy was omitted. RESULTS: The median age of the patients was 10 years (range, 2.5-18 years). Forty-eight (80%) patients had T-cell LBL, and 59 (98.3%) of the patients were stage III/IV. At the end of induction remission Ia (day 33), 3 patients had died of treatment-related toxicity. In the remaining 57 patients, complete remission (CR) or CR undetermined (CRu) had occurred in 47 (82.45%), who were designated as the moderate-risk group and partial remission (PR) had occurred in 10 patients (17.54%), who were designated the high-risk group. All patients experienced grade 3-4 hematological toxicity. At a median follow-up of 35 months, event-free survival was 78.81%+/-0.05 for all patients; the figure was 88.34%+/-0.05 for the moderate-risk group (90.91%+/-0.08 for stage III, 87.68%+/-0.06 for stage IV, 100% for those with B-cell LBL, 84.78%+/-0.06 for those with T-cell LBL, and 82.94%+/-0.08 for stage IV patients with more than 25% blast cells in bone marrow [BM]). The event-free survival in the high-risk group was 60%+/-0.15. CONCLUSION: This modified ALL-BFM-90 protocol is an effective regimen and it greatly improved the survival rate of Chinese children and adolescents with LBL compared with the ALL protocols used previously.

[Dynamic changes of serum proteomic spectra in patients with non-Hodgkin's lymphoma (NHL) before and after chemotherapy and screening of candidate biomarkers for NHL].

BACKGROUND & OBJECTIVE: Although the complete response rate of non-Hodgkin's lymphoma (NHL) is 70%-80% using modern comprehensive treatments, its relapse rate is about 40%-50%. The minimal residual disease (MRD) may be the reason of recurrence. This study was to detect dynamic changes of serum proteomic spectra in NHL patients before and after chemotherapy, thus to screen candidate markers for NHL. METHODS: The proteomic spectra from serum of 44 NHL patients before chemotherapy, 44 NHL patients who achieved complete remission (CR) after chemotherapy, and 51 healthy individuals were analyzed by surface-enhanced laser desorption/ ionization time of flight mass spectrometry (SELDI-TOF-MS) and Ciphergen ProteinChip 3.1 software. RESULTS: Compared with the normal group, one protein peak (M11710) was up-regulated in untreated NHL group, while was close to the normal level in CR group (P < 0.05); nine other protein peaks (M3322, M4355, M6445, M6646, M8581, M8708, M8918, M13959, M15149) were down-regulated in untreated NHL group, while were close to normal levels in CR group(P < 0.05). Five candidate biomarkers for NHL were screened using the decision tree model. CONCLUSIONS: Expressions of serum proteomic spectra are different before and after chemotherapy in NHL patients. Protein signatures of NHL may be screened using SELDI mass spectrometry combined with ProteinChip software. Those signatures may be helpful in screening MRD, detecting early recurrence and predicting the response to treatments.

[Clinical characteristics and prognosis of triple-negative breast cancer: a report of 305 cases].

BACKGROUND & OBJECTIVE: Triple-negative breast cancer is defined by a lack of expression of estrogen receptor, progesterone receptor, and HER2/neu, and considered to be a clinicopathologic entity with aggressive behaviors and poor prognosis. No satisfactory treatment is available. This study was to analyze the clinical characteristics and prognostic factors of the patients with triple-negative breast cancer. METHODS: Clinical data of 1,280 patients with histopathologically confirmed resectable breast cancer, treated at Cancer Center of Sun Yat-sen University from Jan. 2000 to Dec. 2004, were analyzed. Of the 1,280 patients, 305 (23.8%) were confirmed to be triple-negative breast cancer. The clinical characteristics, recurrence and survival of the patients were summarized. RESULTS: Triple-negative breast cancer was commonly seen in young patients, with large masses, a high proportion of lymph node metastasis and familial history of breast cancer at diagnosis. By Jun. 2007, the median time of follow-up was 52 months (range, 28-89 months). Of the 1,280 patients, 234 had local recurrence and metastasis, and 94 died. There was no significant difference in local recurrence between triple-negative and non-triple-negative breast cancer patients. However, the occurrence rates of lung metastasis (HR= 4.41, P<0.001) and liver metastasis (HR=2.13, P=0.006) were significantly higher in triple-negative breast cancer patients than in non-triple-negative breast cancer patients. The 5-year disease-free and overall survival rates were significantly lower in triple-negative breast cancer patients than in non-triple-negative breast cancer patients (73.7% vs. 80.8%, P=0.025; 88.5% vs. 92.8%,P=0.010). Multivariate Cox regression analysis showed that tumor size and lymph node state were prognostic factors of triple-negative breast cancer patients. CONCLUSIONS: Nearly one fourth of breast cancer patients in China are triple-negative breast cancer patients. These patients are usually young, with large masses, lymph node metastasis, and family history of breast cancer. Lung metastasis and liver metastasis may be the main reason of poor prognosis of triple-negative breast cancer.

[Correlation of tumor vessel function to synergistic antitumor effect of Avastin combined cyclophosphamide].

BACKGROUND & OBJECTIVE: Dysfunction of tumor vessels renders high interstitial pressure, hypoxia and acidosis, causing the barrier of cytotoxic efficacy of chemotherapeutic agents. This study was to observe the dynamic alteration of vessel function in neuroblastoma (NB) after treatment of Avastin, and explore the correlation of tumor vessel function to synergistic antitumor effect of Avastin plus cyclophosphamide (CPM). METHODS: Human NB cells were incubated and transplanted into nude mice to form NB xenografts. Avastin at a dose of 5 mg/kg was administered to the mice through the tail veins. The mice were killed on the 6th hour, 3rd day, 6th day and 9th day after Avastin treatment, separately. Tumor vessel function was tested with fluorescein Hoechst33342 staining. NB-bearing mice were treated with Avastin plus CPM. The synergistic antitumor effects were compared when CPM was administered simultaneously with Avastin (combined regimen I) or at the time the tumor vessel function was mostly improved after Avastin administration (combined regimen II). RESULTS: The tumor vessel function was mostly improved on the 6th day after Avastin treatment. Tumor inhibition rates were 36.4% in Avastin monotherapy group, 38.2% in CPM monotherapy group, 55.9% in combined regimen I group, and 66.8% in combined regimen II group at 3 weeks after treatment. The synergistic antitumor effect was better when CPM was administered on the 6th day after Avastin treatment as compared with it used simultaneously with Avastin (P<0.05). CONCLUSION: The synergistic antitumor effect can be augmented when CPM is administered at the time the tumor vessel function is mostly improved after Avastin treatment.

[Clinical analysis of 69 cases of Burkitt's lymphoma].

BACKGROUND & OBJECTIVE: Burkitt's lymphoma is a kind of highly aggressive B-cell lymphoma. Its clinical characteristics are different between the endemic areas in Africa and the sporadic areas in America and Europe. There is no large-scale report concerning Burkitt's lymphoma in China yet. This study was to summarize the characteristics of Burkitt's lymphoma in China. METHODS: Clinical data of 69 Burkitt's lymphoma patients, treated from May 1985 to May 2007 in Cancer Center of Sun Yat-sen University, were analyzed. RESULTS: Of the 69 patients, 44 were men and 25 were women, with a median age of 7 (range, 2-72); 5 were at stage I, 9 at stage II, 21 at stage III, and 34 at stage IV, advanced stage (stages III and IV) accounted for 55 (79.7%) patients. Abdomen (63.8%), cervical lymph nodes (68.1%) and faciomaxillary-oropharynx (34.8%) were the most common involved sites. Bone marrow (21.9%) and central nervous system (17.4%) could also be involved. B symptoms were found in 34 patients. Serum lactate dehydrogenase (LDH) level was elevated in 42 of 58 patients, while serum uric acid level was elevated in 13 of 56 patients. Hepatitis B virus (HBV) infection was found in 6 of 57 patients, Epstain-Barr virus (EBV) infection in 7 of 13 patients, human immunodeficiency virus (HIV) infection in 0 of 51 patients. Short-term and high intensive chemotherapy with central nervous system prophylaxis could improve the prognosis. CONCLUSION: The clinical characteristics of these 69 Burkitt's lymphoma patients are much similar to those from sporadic areas, but the median age is lower, and the most common involved sites are cervical lymph nodes, abdomen and faciomaxillary-oropharynx.

[Efficacy of modified B-NHL-BFM-90 protocol on Burkitt's lymphoma in Chinese children and adolescents].

BACKGROUND & OBJECTIVE: Burkitt's lymphoma is an aggressive non-Hodgkin's lymphoma (NHL) and often involves bone marrow and central nerve system. The efficacy of CHOP regimen on Burkitt's lymphoma is poor. The optimal chemotherapy regimen needs to be investigated. This study was to evaluate the efficacy of modified B-NHL-BFM-90 protocol on Burkitt's lymphoma in children and adolescents, and observe the survival status. METHODS: From Oct. 1999 to Nov. 2006, 31 untreated Burkitt's lymphoma patients aged less than 20 were enrolled. The median age of these patients was 5 (range, 1.5-20 years old). Of the 31 patients, 20 (64.5%) were male, 11 (35.5%) were female. According to St Jude staging system, 1 (3.2%) was at stage I, 6 (19.4%) at stage II, 8 (25.8%) at stage III, 16 (51.6%) at stage IV; 24 (77.4%) were at stage III/IV. According to clinical stage, lactate dehydrogenase (LDH) level and treatment response, these patients were divided into low, moderate and high risk groups. They received modified B-NHL-BFM-90 protocol: cytotoxic drugs such as cyclophosphamide, vincristine, ifosfamide, etoposide, adriamycin, HD-methotrexate, vindesin, dexamethasone, cytarabinec/HD-cytarabine and intrathecal injection. RESULTS: One patient died of tumor lysis syndrome during prophase. The efficacy was evaluable in 30 patients. Of the 30 patients, 25 (83.3%) achieved complete remission (CR), 3 (10.0%) achieved partial remission (PR), 2 (6.7%) had progressive disease (PD)û 1 had tumor relapse. Grade 3-4 myelosuppression occurred in most patients and were recovered by active support care and did not affect next course of chemotherapy. At a median follow-up of 33 months (range, 3-98 months), the 3-year event-free survival (EFS) rate was 86.0% for all patients, with 100% for stage I/II patients and 82.1% for stage III/IV patients, 100% for low risk group, 92.0% for moderate risk group, and 70.0% for high risk group. CONCLUSIONS: Modified B-NHL-BFM-90 protocol can improve the responses and survival of Burkitt's lymphoma in Chinese children and adolescents, with tolerable toxicity. It should be used in the experienced cancer center and hematological unit.

[Feasibility to treat pediatric cancer pain with analgesics for adults and their efficacy].

BACKGROUND & OBJECTIVE: Lacking enough knowledge of pediatric cancer pain and pediatric dosage form of analgesics, current treatment of pediatric cancer pain in China is unsatisfactory. This study was to probe the efficacy and safety of treating pediatric cancer pain with analgesics for adults through summarizing the experience of diagnosis and treatment in Cancer Center of Sun Yet-sen University. METHODS: Basing on the components and the endurable dosage of each component for children, we formulated the appropriate dosage and usage of a few analgesics (including sustained release tablets of morphine, oxycodone and transdermal fantanyl) available in China, most of which were used in adults. Cancer pain of 139 children with newly diagnosed tumors were treated according to the World Health Organization (WHO) analgesic ladder, including 19 cases of mild pain, 41 cases of moderate pain and 79 cases of severe pain. Efficacy and adverse events were evaluated. RESULTS: Of the 139 patients, 104 (74.8%) were treated with analgesics of 1 WHO ladder step, 35 (25.2%) were treated with increased WHO ladder steps (ladder 1-->2 or 2-->3) or reduced WHO ladder steps (ladder 3-->2 or 2-->1). The total response rate for pain relief was 100%: 129 (92.8%) patients had complete relief, 7 (5.0%) had obvious relief, 3(2.2%) had moderate relief. The median time for pain control was 5 days (range, 1-12 days). Sustained release tablets of morphine, transdermal fantanyl, and sustained release tablets of oxycodone were used in 20, 28, and 40 patients, respectively. The median ages of the 3 groups were 10 (5-18), 6 (2.3-16), and 5 (2.5-16) years, respectively. The median of maximum dosages of the 3 single drugs were 20 (10-70) mg, 25 (12.5-50) microg/h, and 10 (5-30) mg, respectively. The median doses used in the 3 groups were 100 (20-360) mg, 5 (1.25-7.5) mg, and 60 (10-200) mg, respectively. The non-steroid anti-inflammatory drug-induced adverse events were nausea and vomiting with very low frequencies. The weak opioid and strong opioid drug-induced adverse events included constipation, nausea, vomiting, and somnolence, all of which were reversible. No severe adverse events, including respiratory depression and drug addiction, happened. CONCLUSIONS: The WHO ladder approach for cancer pain is appropriate for children. Currently in China, most analgesics for adults could be used for pediatric cancer pain treatment.