Li-qun Zou

Induction of apoptosis by norcantharidin in human colorectal carcinoma cell lines: involvement of the CD95 receptor/ligand

Abstract.Purpose: Cantharidin, a natural toxin, is the active substance of mylabris and has antitumor effects in man. Norcantharidin, the demethylated analogue of cantharidin, has been used in the treatment of patients with primary hepatoma and those with leukopenia in China. The present study was designed to investigate whether norcantharidin exerts cytotoxic activity against colorectal cancer cells by inducing apoptosis and to examine the possible mechanism in the phenomenon. Methods: Inhibition of proliferation of norcantharidin on Colo205, HT-29, and SW480 colorectal cancer cells was determined by the trypan blue dye exclusion test. Apoptosis of norcantharidin-treated cells was determined by morphological analysis, agarose gel DNA electrophoresis, and quantitated by flow cytometry after staining with propidium iodide. Cell cycle and the cell surface expression of the CD95/CD95 ligand were evaluated by flow cytometry. Caspase 8-like protease and protein phosphatase 1 and 2A activities were also analyzed. Results: Treatment with norcantharidin of colorectal cancer cells not only inhibited cell proliferation, but also induced apoptosis. Norcantharidin induced apoptosis mainly in two phases: rapid apoptosis in S-phase cells and delayed apoptosis in G2/M arrested cells. Treatment with norcantharidin resulted in an upregulation of the CD95 receptor and CD95 ligand on the cell surface. Furthermore, stimulation with anti-CD95 monoclonal antibody (mAb) resulted in further induction of apoptosis after treatment with norcantharidin. In addition, the apoptosis-inducing effect of norcantharidin was almost completely inhibited by anti-CD95 ligand mAb. Norcantharidin-treated cells showed the activation of caspase 8. Both zVAD-FMK (a broad range caspase inhibitor) and IETD-FMK (a caspase-8 inhibitor) showed apparent inhibition of the apoptosis-inducing effect. Norcantharidin did not show an inhibitory effect on protein phosphatase. Conclusions: These results suggest that norcantharidin triggers apoptosis in colorectal cancer cell lines via the activation of the CD95 receptor/ligand system, and that this agent may be useful for developing new therapeutic regimens for the treatment of colorectal carcinoma.

Phase 2 trial of "sandwich" L-asparaginase, vincristine, and prednisone chemotherapy with radiotherapy in newly diagnosed, stage IE to IIE, nasal type, extranodal natural killer/T-cell lymphoma.

Extranodal natural killer/T‐cell lymphoma (ENKTL), nasal‐type, is a distinct entity of lymphoid tissue. ENKTL is sensitive to radiotherapy (RT), but the prognosis is poorer than for other types of early lymphoma. The treatment schedule is controversial.

Clinical characteristics of 45 patients with invasive pulmonary aspergillosis: retrospective analysis of 1711 lung cancer cases.

Invasive aspergillosis (IA) is a common complication in patients with hematologic malignancies. Patients with solid tumors also are at risk for IA because they may develop neutropenia as a result of chemotherapy and radiotherapy. However, studies of IA in patients with solid tumors are rare. In this study, the risk factors and clinical characteristics of pulmonary infection and death mediated by invasive pulmonary aspergillosis (IPA) as complications in patients with lung cancer were determined.

Gemcitabine and cisplatin in advanced nasopharyngeal carcinoma: a pilot study.

A pilot study was performed to evaluate the efficacy and safety of gemcitabine and cisplatin combination in the treatment of patients with metastatic nasopharyngeal carcinoma (NPC). Eligible patients were those with metastatic NPC who had been treated with radiotherapy and cisplatin plus 5-fluorouracil chemotherapy. Cisplatin was given intravenously at the fixed dose of 30 mg/m2 on days 1–3. Gemcitabine was intravenously administered over 30 min infusion with the dose escalated from 800 to 1200 mg/m2 on days 1 and 8. The 3-week schedule defined a cycle of treatment. Fifteen patients were enrolled and assessed for the worst toxicities. For a total of 83 cycles, Grade 3–4 toxicity was 46.7% for neutropenia, 40.0% for thrombocytopenia, and 20.0% for anemia. Grade 3 nonhematologic toxicity was 13.3%. Fourteen patients were assessable for response. The overall response rate was 92.9%, with complete response in three patients (21.4%). Median survival was 10.2 months. Seven patients had lived more than one year, and two patients had lived more than 2 years. The recommended dose of gemcitabine was 1000 mg/m2 on days 1 and 8 in each cycle. In conclusion, the present combination is well tolerated and highly active in the treatment of advanced NPC patients.

Measurement of distress in Chinese inpatients with lymphoma

The aim of this study was to assess the levels and sources of distress in patients with lymphoma. This study also focused on the influence of factors of the level of distress and the cutoff score using the Distress Thermometer (DT) relative to the Hospital Anxiety and Depression Scale (HADS).

Survey on breast cancer patients in China toward breast‐conserving surgery

Objective: We sought to investigate attitudes toward breast‐conserving therapy (BCS) in early‐stage breast cancer (EBC) patients from P. R. China and assess the factors influencing their decision.

Five-year analysis from phase 2 trial of "sandwich" chemoradiotherapy in newly diagnosed, stage IE to IIE, nasal type, extranodal natural killer/T-cell lymphoma.

The “sandwich” protocol, was first proposed by us and comprised of l‐asparaginase, vincristine, and prednisone chemotherapy with radiotherapy, results in 2‐year overall survival and progression‐free survival rates that surpass traditional therapies for patients with newly diagnosed, stage IE‐IIE, nasal type, extranodal natural killer/T‐cell lymphoma. The results had been published by cancer. These patients were followed up over a median period of 67 months, for which updates and the results of prognostic factors analyses are presented. The 5‐year overall survival and progress‐free survival rates were both 64%. The highest rates of death occurred during the first 6 months, and between the second and third year after enrollment. The initial therapeutic response (odds ratio = 5.83; P = 0.001) and B symptoms (odds ratio = 6.13; P = 0.043) were significant prognostic factors for overall survival. However, the international prognostic index was not significant for progress‐free survival and overall survival. There were no severe long‐term side effects. These results indicate that the “sandwich” protocol may benefit the long‐term survival of patients with newly diagnosed stage IE‐IIE, nasal type, extranodal natural killer/T‐cell lymphoma. However, additional studies with larger samples are required to confirm these results. This study is registered at www.Chictr.org (ChicTR‐TNC‐09000394).

Prognostic Characteristics of Gastrointestinal Tract Nk/t-cell Lymphoma: An Analysis of 47 Patients in China

Background: The gastrointestinal tract is the most common primary site of extranodal lymphomas, whereas gastrointestinal natural killer/T-cell (GINKT) lymphomas are relatively rare. To date, neither the prognostic characteristics nor the clinical features or optimal therapeutic approach for GINKT has yet been defined. Patients and Methods: In this study, a retrospective analysis was carried out on clinical data obtained from 47 patients diagnosed with GINKT lymphoma between May 1999 and August 2011 at West China Hospital. Results: Patients had a median age of 37 years. Thirty-five of the patients were men (74.5%). The common clinical manifestations included fever (78.7%) and abdominal pain (76.6%). Seventeen patients had intestinal perforation (36.2%). All patients showed ulcerative lesions; the most common site of involvement was the colon (27/47; 57.4%), followed by the jejunoileum and ileocecum (14/47; 29.8%). The median survival period was 2.83 (95% confidence interval, 0.27-29) months. Age, perforation, B syndrome, staging according to Lugano system, and surgery were independent prognostic risk factors for GINKT lymphoma. Conclusions: This study concluded that GINKT lymphoma is prone to perforation, hemorrhage, and other complications; moreover, the prognosis is very poor. The Lugano staging is a relatively suitable staging system. Surgery before perforation is a key therapy factor that affected prognosis. Although the roles played by chemotherapy and radiotherapy are unclear, combination therapy is necessary.

A phase II prospective study of the “Sandwich” protocol, L-asparaginase, cisplatin, dexamethasone and etoposide chemotherapy combined with concurrent radiation and cisplatin, in newly diagnosed, I/II stage, nasal type, extranodal natural killer/T-cell lymphoma

Nasal-type, extranodal NK/T cell lymphoma (ENKTCL) is a special type of lymphomas with geographic and racial specificity. Up to now, the standard first-line treatment is still not unified. In our previous report, the “sandwich” protocol produced good results. Continuing to use the “sandwich” mode, a new chemotherapy composed of L-asparaginase, cisplatin, etoposide and dexamethasone (LVDP) plus concurrent chemoradiotherapy (CCRT) was conducted in more patients with newly diagnosed, I/II stage ENKTCL. The results showed that 66 patients were enrolled. Overall response rate was 86.4% including 83.3% complete response and 3.0% partial remission. With the median follow-up of 23.5 months, 3-year overall survival and 3-year progression-free survival were 70.1% and 67.4%, respectively. The survival rate in stage II and extra-cavity stage I was significantly less than that in limited stage I (p < 0.05). Therefore, we thought that the “sandwich” mode was worthy of being generalized and LVDP combined with CCRT was an effective protocol for I/II stage ENKTCL. But this regimen was not suitable for all stage I/II patients and warrants larger sample and layering investigation. This study was a registered clinical trial with number ChiCTR-TNC-12002353.

The role of palliative chemotherapy for terminally ill patients with advanced NSCLC

Background:  To evaluate the conditions of palliative chemotherapy in terminally ill patients with advanced non‐small cell lung cancer (NSCLC), and to discuss the potential factors that affect the prognosis of these patients.