Progress of biotherapy in gastrointestinal carcinomas / 中华胃肠外科杂志

Gastrointestinal carcinomas are among the malignancies with highest morbidity and mortality. The survival rates of these tumors remain pretty low in spite of advancements of traditional treatments. As the fourth treatment method besides surgery, radiotherapy and chemotherapy, biotherapy has shown promising prospect in improving the prognosis of gastrointestinal carcinomas. In this manuscript, we summarized the current progress of biotherapy in gastrointestinal tumors including gene therapy, immune therapy and molecular targeted therapy.

Safety of in vitro amplified HLA-haploidentical donor immune cell infusions for childhood malignancies / 癌症

In vitro amplified human leukocyte antigen (HLA)-haploidentical donor immune cell infusion (HDICI) is not commonly used in children. Therefore, our study sought to evaluate its safety for treating childhood malignancies. Between September 2011 and September 2012, 12 patients with childhood malignancies underwent HDICI in Sun Yat-sen University Cancer Center. The median patient age was 5.1 years (range, 1.7-8.4 years). Of the 12 patients, 9 had high-risk neuroblastoma (NB) [7 showed complete response (CR), 1 showed partial response (PR), and 1 had progressive disease (PD) after multi-modal therapies], and 3 had Epstein-Barr virus (EBV)-positive lymphoproliferative disease (EBV-LPD). The 12 patients underwent a total of 92 HDICIs at a mean dose of 1.6×10(8) immune cells/kg body weight: 71 infusions with natural killer (NK) cells, 8 with cytokine-induced killer (CIK) cells, and 13 with cascade primed immune cells (CAPRIs); 83 infusions with immune cells from the mothers, whereas 9 with cells from the fathers. Twenty cases (21.7%) of fever, including 6 cases (6.5%) accompanied with chills and 1 (1.1%) with febrile convulsion, occurred during infusions and were alleviated after symptomatic treatments. Five cases (5.4%) of mild emotion changes were reported. No other adverse events occurred during and after the completion of HDIDIs. Neither acute nor chronic graft versus host disease (GVHD) was observed following HDICIs. After a median of 5.0 months (range, 1.0-11.5 months) of follow-up, the 2 NB patients with PR and PD developed PD during HDICIs. Of the other 7 NB patients in CR, 2 relapsed in the sixth month of HDICIs, and 5 maintained CR with disease-free survival (DFS) ranging from 4.5 to 11.5 months (median, 7.2 months). One EBV-LPD patient achieved PR, whereas 2 had stable disease (SD). Our results show that HDICI is a safe immunotherapy for childhood malignancies, thus warranting further studies.

Effect of anti-asthma Chinese medicine Chuankezhi on the anti-tumor activity of cytokine-induced killer cells / 癌症

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 interferon-gamma (IFN-γ) and interleukin 2. Different concentrations of CKZ were added on day 2. After incubation for 14 days in culture, the antitumor 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 antitumor activity of CIK cells in nude mice was also investigated. CKZ increased the percentage of CD3+CD56+ CIK cells but did not significantly change the percentage of CD4+, CD8+, or CD4+CD25+ CIK cells. CKZ-conditioned CIK cells showed a greater ability to kill tumor cells, 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 in vivo than the CIK, CKZ, or normal saline control groups. Our results indicate that CKZ enhances the antitumor activity of CIK cells and is a potential medicine for tumor immunotherapy.

Effect of silencing epidermal growth factor receptor expression by RNA interference on the growth of nasopharyngeal carcinoma cell 5-8F / 南方医科大学学报

<p><b>OBJECTIVE</b>To observe the growth and cell cycle changes of nasopharyngeal carcinoma cell 5-8F in response to silencing of the expression of epidermal growth factor receptor (EGFR) with RNA interference (RNAi), and explore the possible relationships between EGFR and the occurrence, differentiation and progression of nasopharyngeal carcinoma.</p><p><b>METHOD</b>Three EGFR-specific small interfering RNAs (siRNAs) were obtained by in vitro transcription and synthesis and were transiently transfected into 5-8F cells. The EGFR expression levels in the transfected cells were detected by reverse transcription (RT)-PCR and Western blotting, respectively. After EGFR expression silencing, the growth and cell cycle changes of the cells were observed.</p><p><b>RESULTS</b>EGFR mRNA contents and protein levels decreased by approximately 67.5% and 77%, respectively, after RNAi of 5-8F cells, and the cell proliferation decreased and cell cycle arrest at G1 phase occurred in association with EGFR silencing.</p><p><b>CONCLUSION</b>EGFR silencing by RNAi can reduce the proliferation of nasopharyngeal carcinoma cells and induce cell cycle arrest at G1 phase, which sheds light on the possible use of RNAi for further investigation of the pathogenesis and gene therapy of nasopharyngeal carcinoma.</p>

Primary diffuse large B-cell lymphoma of the heart: a clinicopathological study / 南方医科大学学报

<p><b>OBJECTIVE</b>To define the clinicopathological features of primary cardiac large B-cell lymphoma.</p><p><b>METHOD</b>A case of primary cardiac large B-cell lymphoma was studied with conventional histopathological and immunohistochemical staining in combination with literature review.</p><p><b>RESULTS</b>The lesion appeared to originate in the right atrium and involved the venae cavae and the left atrium. Microscopic examination showed diffuse proliferation of large atypical lymphocytes with abundant cytoplasm, vestiealer nuelei, thick nuclear membrane and conspicuous nucleoli. Giant tumor cells scattered in the lesion. The neoplastic cells were positive for CD20 and CD79a.</p><p><b>CONCLUSION</b>Primary cardiac lymphoma is extremely rare, and its pathogenesis remains unclear. With non-specific clinical manifestations, the majority of primary cardiac lymphomas are of B-cell lineage and a bad prognosis.</p>

Study on etiology and pathology of severe acute respiratory syndrome / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the clinicopathologic characteristics of severe acute respiratory syndrome (SARS).</p><p><b>METHODS</b>Three autopsy cases were studied retrospectively. Routine HE stain was used to study all the cases. Part of the lung tissue specimens were studied further with Macchiavello's stain, viral inclusion body stain, reticulin and PAS stains, immunohistochemistry, thin sections with staining, light microscopy and transmission electronic microscope investigation.</p><p><b>RESULTS</b>The earliest symptom of all 3 cases was hyperpyrexia and followed by progressive dyspnea and appearance of lung field shadows in X rays findings. Pulmonary lesions included: bilateral and extensive consolidation, localized hemorrhage and necrosis, desquamative alveolitis and bronchitis, alveolar proliferation and desquamation, accumulation of protein exudates, mononuclear cells, lymphocytes, and plasma cells as well as hyaline membrane formation in alveoli and viral inclusion bodies were seen in the alveolus epithelial cells. The exudated organization tended to become glomeruloid organizing pneumonitis in a few avaoli. Lesions of the immune organs included: large patchy necrosis in the spleens and localized necrosis in the lymph nodes were seen. Bone marrow became restrained. There were lesions of systemic small vasculitis including edema of the perivascular tissue and vascular wall of the small veins with localized fibrinoid necrosis distributing in the heart, lungs, kidneys, adrenal glands and the striated muscles accompanying with mononuclear cells and lymphocytes infiltration. Thrombosis was seen in part of the small veins. In addition, there were also the systemic poisonous changes including: degeneration and necrosis of the parenchyma cells in lungs, liver, kidneys, heart and adrenals. Electronic microscopy demonstrated clusters of virus particles seen in the lung tissue.</p><p><b>CONCLUSION</b>SARS is a systemic disease. Lungs, immune system and systemic small vessels are the main target organs attacked by the virus. Extensive consolidation of lungs, formation of hyaline membrane to a large extent, respiratory distress and decrease of immune function are the main causes of death.</p>