Erratum: Non-canonical signaling pathway of SNAI2 induces EMT in ovarian cancer cells by suppressing miR-222-3p transcription and upregulating PDCD10: Erratum.

[This corrects the article DOI: 10.7150/thno.43198.].

Transport Behavior of Cd2+ in Highly Weathered Acidic Soils and Shaping in Soil Microbial Community Structure.

The mining and smelting site soils in South China present excessive Cd pollution. However, the transport behavior of Cd in the highly weathered acidic soil layer at the lead-zinc smelting site remains unclear. Here, under different conditions of simulated infiltration, the migration behavior of Cd2+ in acid smelting site soils at different depths was examined. The remodeling effect of Cd2+ migration behavior on microbial community structure and the dominant microorganisms in lead-zinc sites soils was analyzed using high-throughput sequencing of 16S rRNA gene amplicons. The results revealed a specific flow rate in the range of 0.3-0.5 mL/min that the convection and dispersion have no obvious effect on Cd2+ migration. The variation of packing porosity could only influence the migration behavior by changing the average pore velocity, but cannot change the adsorption efficiency of soil particles. The Cd has stronger migration capacity under the reactivation of acidic seepage fluid. However, in the alkaline solution, the physical properties of soil, especially pores, intercept the Cd compounds, further affecting their migration capacity. The acid-site soil with high content of SOM, amorphous Fe oxides, crystalline Fe/Mn/Al oxides, goethite, and hematite has stronger ability to adsorb and retain Cd2+. However, higher content of kaolinite in acidic soil will increase the potential migration of Cd2+. Besides, the migration behavior of Cd2+ results in simplified soil microbial communities. Under Cd stress, Cd-tolerant genera (Bacteroides, Sphingomonas, Bradyrhizobium, and Corynebacterium) and bacteria with both acid-Cd tolerance (WCHB 1-84) were distinguished. The Ralstonia showed a high enrichment degree in alkaline Cd2+ infiltration solution (pH 10.0). Compared to the influence of Cd2+ stress, soil pH had a stronger ability to shape the microbial community in the soil during the process of Cd2+ migration.

New application of Aspergillus versicolor in promoting plant growth after suppressing sterigmatocystin production via genome mining and engineering.

Aspergillus genus is a key component in fermentation and food processing. However, sterigmatocystin (STE)-a mycotoxin produced by several species of Aspergillus-limits the use of some Aspergillus species (such as Aspergillus versicolor, Aspergillus inflatus, and Aspergillus parasiticus) because of its toxicity and carcinogenicity. Here, we engineered an STE-free Aspergillus versicolor strain based on genome mining techniques. We sequenced and assembled the Aspergillus versicolor D5 genome (34.52 Mb), in which we identified 16 scaffolds and 54 biosynthetic gene clusters (BGCs). We silenced cytochrome P450 coding genes STC17 and STC27 by insertional inactivation. The production of STE in the Δstc17 mutant strain was increased by 282% but no STE was detected in the Δstc27 mutant. Metabolites of Δstc27 mutant exhibited growth-promoting effect on plants. Our study makes significant progress in improving the application of some Aspergillus strains by restricting their production of toxic and carcinogenic compounds.

Clinical Impact of 11q13.3 Amplification on Immune Cell Infiltration and Prognosis in Breast Cancer.

Introduction: Amplification of the 11q13.3 locus has been observed in various tumors. This study sought to determine the correlation of gene amplification at the 11q13.3 locus with the immune status and survival of breast cancer. Methods: Amplification of the 11q13.3 locus was characterized by analyzing a publicly available database from the cBioPortal platform (TCGA). The correlation of amplified genes with immune cell infiltration in breast cancer was further analyzed using the TIMER2.0 platform. Immunohistochemical staining was used to determine the expression levels of Cyclin D1 (CCND1), Fas-associated death domain (FADD) and P53 in 156 clinical breast cancer samples. Results: This study revealed that amplification of the 11q13.3 amplicon in breast cancer is likely more frequently detected in luminal B breast cancer. Moreover, high expression or amplification of CCND1, fibroblast growth factor 3 (FGF3), fibroblast growth factor 4 (FGF4), fibroblast growth factor 19 (FGF19) and FADD was inversely correlated with the abundance of CD4+ T cells and dendritic cell infiltration in breast cancer (P < 0.05). Data analysis also demonstrated that high expression of CCND1, FGF4 and FADD mRNA levels was closely correlated with shorter recurrence-free survival (RFS) in patients with breast cancer (P < 0.05). The results of immunohistochemical staining from clinical samples further confirmed that high expression of CCND1 and FADD was frequently detected in luminal B and high-grade breast cancer with shorter metastasis-free survival times (P < 0.05). Conclusion: This study demonstrated that coamplification of genes located on the 11q13.3 amplicon is frequently detected in luminal B subtype breast cancer and is closely associated with worse survival in patients with breast cancer. Moreover, coamplification of the CCND1-FGF locus might decrease antitumor immune activity in breast cancer, indicating that coamplification of the 11q13.3 amplicon is likely to be a key determinant of therapeutic resistance and accelerate the aggressive evolution of breast cancer.

Downregulation of MEIS1 mediated by ELFN1-AS1/EZH2/DNMT3a axis promotes tumorigenesis and oxaliplatin resistance in colorectal cancer.

Oxaliplatin is widely used in the frontline treatment of colorectal cancer (CRC), but an estimated 50% of patients will eventually stop responding to treatment due to acquired resistance. This study revealed that diminished MEIS1 expression was detected in CRC and harmed the survival of CRC patients. MEIS1 impaired CRC cell viabilities and tumor growth in mice and enhanced CRC cell sensitivity to oxaliplatin by preventing DNA damage repair. Mechanistically, oxaliplatin resistance following MEIS1 suppression was critically dependent on enhanced FEN1 expression. Subsequently, we confirmed that EZH2-DNMT3a was assisted by lncRNA ELFN1-AS1 in locating the promoter of MEIS1 to suppress MEIS1 transcription epigenetically. Based on the above, therapeutics targeting the role of MEIS1 in oxaliplatin resistance were developed and our results suggested that the combination of oxaliplatin with either ELFN1-AS1 ASO or EZH2 inhibitor GSK126 could largely suppress tumor growth and reverse oxaliplatin resistance. This study highlights the potential of therapeutics targeting ELFN1-AS1 and EZH2 in cell survival and oxaliplatin resistance, based on their controlling of MEIS1 expression, which deserve further verification as a prospective therapeutic strategy.

Transcriptome Profiles Reveal the Growth-Promoting Mechanisms of Paenibacillus polymyxa YC0136 on Tobacco (Nicotiana tabacum L.).

Paenibacillus polymyxa is an important member of the plant growth-promoting rhizobacteria. P. polymyxa YC0136 inoculation had beneficial effect on growth promotion and biological control of tobacco (Nicotiana tabacum L.) under field conditions. This study aimed to reveal the growth-promoting mechanisms of strain YC0136. In growth-promotion assays, tobacco plant height was increased by 8.42% and 8.25% at 60 and 90 days, respectively, after inoculation with strain YC0136. Strain YC0136 also promoted the accumulation of tobacco biomass in varying degrees. Following inoculation with strain YC0136, 3,525 and 4,368 tobacco genes were up-regulated and down-regulated, respectively. Strain YC0136 induced the expression of plant hormone-related genes in tobacco, including auxin, cytokinin, and gibberellin, as well as transcription factors related to stress resistance such as WRKY and MYB. In addition, strain YC0136 induced the up-regulation of genes in the phenylpropanoid biosynthesis pathway by 1.51-4.59 times. Interaction with tobacco also induced gene expression changes in strain YC0136, with 286 and 223 genes up-regulated and down-regulated, respectively. Tobacco interaction induced up-regulation of the ilvB gene related to auxin biosynthesis in strain YC0136 by 1.72 times and induced expression of some nutrient transport genes. This study contributes to our understanding of the growth-promoting mechanisms of strain YC0136 on tobacco and provides a theoretical basis for the application of P. polymyxa YC0136 as a biological fertilizer.

HOXC10 promotes tumour metastasis by regulating the EMT-related gene Slug in ovarian cancer.

The mortality rate of ovarian cancer is the highest among gynaecological cancers, primarily due to metastatic symptoms. Recent studies have shown that HOX genes are crucial in tumour progression, but the underlying mechanisms remain unclear. Here, HOXC10 expression was examined in ovarian cancer tissues. The function of HOXC10 in ovarian cancer metastasis was investigated in vitroand via intraperitoneal injection in vivo. A total of 158 ovarian cancer patients with adequate records were enrolled for analysis. HOXC10 was associated with metastasis and poor prognosis in ovarian cancer. In vitro, HOXC10 overexpression promoted ovarian cancer cell migration. Moreover, HOXC10 positively regulated Slug expression, altering the migration ability of cancer cells. Furthermore, our study showed that miR-222-3p was a suppressor of HOXC10. In vivo, a decrease in hepatic metastasis was seen in xenograft mice harbouring tumours with stable HOXC10 overexpression after miR-222-3p agomir (an overexpression reagent) injection. This study provides the first evidence that HOXC10 promotes ovarian cancer metastasis by regulating the transcription of the EMT-related gene Slug. Moreover, we found that HOXC10 is regulated by miR-222-3p. These data highlight the crucial role of HOXC10 in enhancing ovarian cancer metastasis and may provide a therapeutic target for ovarian cancer.

Non-canonical signaling pathway of SNAI2 induces EMT in ovarian cancer cells by suppressing miR-222-3p transcription and upregulating PDCD10.

Background: Epithelial ovarian cancer (EOC) is one of the most lethal malignancies in women worldwide. Many studies showed the transcription factor SNAI2-induced Epithelial-Mesenchymal Transition (EMT) through inhibiting E-cadherin (E-cad) expression. Our previous study reported that miR-222-3p was an important tumor-suppressive miRNA for EOC development and dissemination. The present study aimed to acquire a deeper mechanistic understanding of the role of miR-222-3p regulation that might contribute to improving current anti-metastasis strategies in EOC. Methods: A variety of techniques were used to measure mRNA and protein expression levels, including quantitative real-time polymerase chain reaction (qRT-PCR), Western blot, immunohistochemical (IHC) staining, and immunofluorescence (IF). Four different microRNA (miRNA) target prediction databases were used to predict the target genes of miR-222. Luciferase assay was performed to determine the direct binding of miR-222-3p to the untranslated region (3'-UTR) of PDCD10. The biological effects of PDCD10 and miR-222-3p were also investigated in vitro by Transwell and wound healing assays, as well as in vivo by a xenograft mice model. Combining UCSC and JASPAR, as well as ENCODE public databases, we predicted that the transcription factor SNAI2 could affect miR-222-3p expression. Luciferase assay was utilized to examine the validity of putative SNAI2 binding sites for miR-222-3p regulation. Chromatin immunoprecipitation (ChIP) was used to explore the SNAI2's occupancy on the miR-222-3p promoter. Results: We observed the inhibitory effect of SNAI2 on miR-222-3p transcription and confirmed the tumor-suppressive function of miR-222-3p both in EOC cells and tissues. PDCD10 was upregulated and inversely correlated with miR-222-3p, both in vitro and in vivo, which was consistent with the information in bioinformatics databases. Furthermore, We observed direct binding of miR-222-3p to the 3'-UTR of PDCD10 and inhibition of PDCD10 translation, which, in turn, inhibited EOC cell migration in vitro and repressed EOC xenografted tumor metastasis in vivo. We found that genetic overexpression of PDCD10 (OE-PDCD10) increased cancer metastasis by down-regulating E-cad and enhancing Vimentin (VIM) thereby inducing EMT and promoting ß-catenin/Wnt-mediated cell migration.

Functions of N6-methyladenosine and its role in cancer.

N6-methyladenosine (m6A) is methylation that occurs in the N6-position of adenosine, which is the most prevalent internal modification on eukaryotic mRNA. Accumulating evidence suggests that m6A modulates gene expression, thereby regulating cellular processes ranging from cell self-renewal, differentiation, invasion and apoptosis. M6A is installed by m6A methyltransferases, removed by m6A demethylases and recognized by reader proteins, which regulate of RNA metabolism including translation, splicing, export, degradation and microRNA processing. Alteration of m6A levels participates in cancer pathogenesis and development via regulating expression of tumor-related genes like BRD4, MYC, SOCS2 and EGFR. In this review, we elaborate on recent advances in research of m6A enzymes. We also highlight the underlying mechanism of m6A in cancer pathogenesis and progression. Finally, we review corresponding potential targets in cancer therapy.

Correction: MiR-4524b-5p/WTX/ß-catenin axis functions as a regulator of metastasis in cervical cancer.

[This corrects the article DOI: 10.1371/journal.pone.0214822.].

MiR-4524b-5p/WTX/ß-catenin axis functions as a regulator of metastasis in cervical cancer.

Cervical cancer is the second most deadly gynecological tumor worldwide. MicroRNAs (miRNAs) play very important roles in tumor oncogenesis and progression. The mechanism of post-transcription regulation of WTX gene is still unknown. A series of differential miRNAs were discovered by microarray analysis comparing three pairs of primary cervical cancer specimens and their relapsed tumors from three patients. Quantitative reverse transcriptase PCR (qRT-PCR), Western Blot (WB) and Immunohistochemistry (IHC) was used to detect the expression of miR-4524b-5p and WTX in cervical cell lines and tissues. The biological function of miR-4524b-5p and WTX was investigated through knockdown and overexpression with inhibitor/siRNA and mimic/plasmid in vitro and in vivo. In this study, we found that miR-4524b-5p is highly expressed in relapsed cervical cancer specimens. Combined in vitro and in vivo experiments, showed that miR-4524b-5p could regulate the migration and invasion ability of cervical cancer. Furthermore, we also found that miR-4524b-5p could regulate the migration and invasion of cervical cancer by targeting WTX and that WTX could regulate the expression of ß-catenin. Taken together, our data identified a miR-4524b-5p/WTX/ß-catenin regulatory axis for cervical cancer, and miR-4524b-5p may be a potential target for cervical cancer therapy.

MiR-221-3p targets ARF4 and inhibits the proliferation and migration of epithelial ovarian cancer cells.

Epithelial ovarian cancer (EOC) is the most lethal gynecologic cancer. Although molecular diagnostic tools and targeted therapies have been developed over the past few decades, the survival rate is still rather low. Numerous researches suggest that some microRNAs (miRNAs) are key regulators of tumor progression. Among those miRNAs that has attracted much attention for their multiple roles in human cancers, the function of miR-221-3p in EOC has not been elucidated. Herein, we examined the expression of miR-221-3p in EOC patients and cell lines. Our data revealed that higher expression of miR-221-3p was linked to better overall survival in EOC patients. In-vitro experiments indicated that miR-221-3p inhibited EOC cell proliferation and migration. By performing subsequent systematic molecular biological and bioinformatic analyses, we found ADP-ribosylation factor (ARF) 4 is one of the putative target genes, the direct binding relationship was further confirmed by dual-luciferase reporter assay. Finally, a distinct gene expression between miR-221-3p and ARF4 in EOC group and normal group was identified, and the negative correlation between their expression levels in EOC specimens was further confirmed. Taken together, our research uncovered the tumor suppressive role of miR-221-3p in EOC and directly targeted ARF4, suggesting that miR-221-3p might be a novel potential candidate for clinical prognosis and therapeutics of EOC.

Synthesis of Size-Tunable Hollow Polypyrrole Nanostructures and Their Assembly into Folate-Targeting and pH-Responsive Anticancer Drug-Delivery Agents.

Chemotherapeutic drugs currently used in clinical settings have high toxicity, low specificity, and short half-lives. Herein, polypyrrole-based anticancer drug nanocapsules were prepared by tailoring the size of the nanoparticles with a template method, controlling drug release by means of an aromatic imine, increasing nanoparticle stability through PEGylation, and improving tumor-cell selectivity by folate mediation. The nanoparticles were characterized by TEM and dynamic light scattering. α-Folate receptor expression levelsof tumor cells and normal cells were investigated by western blot and quantitative polymerase chain reaction analyses. Flow cytometry and fluorescence imaging were used to verify the cell uptake of the different-sized nanoparticles. From the different-sized polypyrrole nanoparticles, the optimally functionalized nanoparticles of 180 nm hydrodynamic diameter were chosen and further usedfor in vitroandin vivotests. The nanoparticles showed excellent biocompatibility and the drug-loaded nanoparticles exhibited effective inhibition of tumor cell growth in vitro. Moreover, the drug-loaded nanoparticles showed substantially enhanced accumulation in tumor regions and effectively inhibitedin vivotumor growth. Furthermore, the nanoparticles showed reduced doxorubicin-induced toxicity andno significant side effects in normal organs of tumor-bearing mice, as measured by body-weight shifts and evaluationof drug distribution. Overall, the functionalized nanoparticles are promising nanocarriers for tumor-targeting drug delivery.

MicroRNA-222-3p/GNAI2/AKT axis inhibits epithelial ovarian cancer cell growth and associates with good overall survival.

Ovarian carcinoma is the most lethal gynecologic tumor worldwide. Despite having developed molecular diagnostic tools and targeted therapies over the past few decades, patient survival is still quite poor. Numerous studies suggest that microRNAs are key regulators of many fundamental biological processes, including neoplasia and tumor progression. miR-222 is one of those miRNAs that has attracted much attention for its multiple roles in human diseases, especially cancer. The potential role of microRNAs in ovarian cancer has attracted much attention in recent years. Some of these microRNAs have been suggested as potential therapeutic targets for EOC patients. In this study, we sought to investigate the biologic functions of miR-222-3p in EOC carcinogenesis. Herein, we examined the expression of miR-222-3p in EOC patients, mouse models and cell lines, and found that higher expression of miR-222-3p was associated with better overall survival in EOC patients, and its level was negatively correlated with tumor growth in vivo. Furthermore, in-vitro experiments indicated that miR-222-3p inhibited EOC cell proliferation and migration, and decreased the phosphorylation of AKT. We identified GNAI2 as a target of miR-222-3p. We also found that GNAI2 promoted EOC cell proliferation, and is an activator of the PI3K/AKT pathway. We describe the characterization of a novel regulatory axis in ovarian cancer cells, miR-222-3p/GNAI2/AKT and its potential application as a therapeutic target for EOC patients.

Multicenter phase II study of capecitabine combined with nedaplatin for recurrent and metastatic nasopharyngeal carcinoma patients after failure of cisplatin-based chemotherapy.

PURPOSE: There is no standard second-line regimen for recurrent and metastatic nasopharyngeal carcinoma patients after failure of cisplatin-based chemotherapy. A multicenter phase II study was conducted to evaluate the efficacy and toxicity of capecitabine combined with nedaplatin for these patients. PATIENTS AND METHODS: In the multicenter, open-label, single-arm phase II study, patients with recurrent and metastatic nasopharyngeal carcinoma who failed to previous cisplatin-based chemotherapy were enrolled. Patients received oral capecitabine (1,000 mg/m(2) twice daily from day 1 to 14) and intravenous nedaplatin (80 mg/m(2), day 1) every 3 weeks for two cycles at least. RESULTS: A total of forty-eight patients were enrolled and included in the intention-to-treat analysis of efficacy and adverse events. Treatment was well tolerated. Grade 3/4 toxicities included neutropenia (8.4 %), anemia (2.1 %), diarrhea (4.2 %), stomatitis (6.3 %), and hand-foot syndrome (HFS) (4.2 %). There were two complete response (4.2 %), eighteen partial responses (37.5 %), giving an overall response rate of 41.7 % [95 % confidence interval (CI) 27.7-55.8]. With a median follow-up period of 12.1 months, the median time to progression was 5.8 months (95 % CI 3.9-7.8 months) and median overall survival was 12.4 months (95 % CI 9.6-16.8 months). CONCLUSION: Capecitabine combined with nedaplatin offers a satisfactory clinical activity and an acceptable safety profile for recurrent and metastatic nasopharyngeal carcinoma patients after failure of cisplatin-based chemotherapy.

[Transdermal fentanyl in treating severe painful mucositis caused by autologous hematopoietic stem cell transplantation].

BACKGROUND & OBJECTIVE: The incidence of mucositis caused by autologous hematopoietic stem cell transplantation (AHSCT) is relatively high. The severe painful mucositis can reduce the quality of life of patients obviously. Transdermal fentanyl is efficient in treating chronic pain of cancer, and also can relieve the severe pain of mucositis resulted from chemotherapy. This study was to investigate the efficacy and safety of transdermal fentanyl for the severe painful mucositis caused by AHSCT. METHODS: A total of 22 malignant tumor patients suffered from severe mucositis caused by high dose chemotherapy combined AHSCT. The analgesic degree before and after treatment was evaluated by the scores of Visual Analogue Scale (VAS) (range 0-10). The median VAS scores of all patients were above 4 (moderate to severe pain) before the administration of transdermal fentanyl. The quality of life before and after treatment was evaluated by the Standard of Quality of Life drew up in China in 1990. The adverse events after treatment were evaluated by Common Toxicity Criteria formulated by National Cancer Institute of the USA. RESULTS: The median VAS score has been decreased from baseline at 6 (4-9) to 3.5 (0-9) on Day 3, 2 (0-6) on Day 5, 0.5 (0-8) on Day 7, 0 (0-6) on Day 10, and 0 (0-5) on Day 15 after treatment (P<0.001). The overall response rate was 100%, while the complete response rate was 45.5%. The quality of life of the patients was improved significantly (P<0.01). The adverse events after treatment of transdermal fentanyl included dizziness, somnolence, dysuria, mild and transient nausea, vomiting, discomfort of stomach, and so on. All the adverse events disappeared within several days after proper managements. Neither severe adverse event nor drug addiction was found. CONCLUSIONS: Transdermal fentanyl has good analgesic effect on painful severe mucositis induced by AHSCT. It is convenient and well tolerated, and could improve quality of life significantly.

[Efficacy of rituximab-containing salvage regimens on relapsed or refractory B-cell non-Hodgkin's lymphoma].

BACKGROUND & OBJECTIVE: The prognosis of relapsed or refractory B-cell lymphoma is poor, with a short-term survival after conventional second-line chemotherapy. Rituximab, a chimeric anti-CD20 antigen, in combination with CHOP or CHOP-like chemotherapy may improve both disease-freely survival and overall survival of naive patients, but it's role in the second-line treatment for relapsed non-Hodgkin's lymphoma (NHL) is uncertain. This study was to evaluate the efficacy of rituximab-containing salvage regimens on relapsed or refractory NHL, and observe the toxicities. METHODS: Clinical data of 35 patients with relapsed or refractory NHL, treated in Cancer Center of Sun Yat-sen University, were analyzed retrospectively. Of the 35 patients, 19 were man, and 16 were women, with a median age of 53.5 years (ranged from 21 to 77); for ECOG performance status, 33 (94.3%) scored 0-1; for international prognostic index (IPI), 20 (57.1%) scored 0-1, 7 (20%) scored 2, 4 (11.4%) scored 3, and 4 (11.4%) scored 4-5; 23 cases of diffuse large B-cell lymphoma (DLBL) accounted for 65.7% among all subtypes. Rituximab (375 mg/m2) was administered intravenously at the day before each chemotherapy cycle. The second-or third-line salvage regimens included EPOCH, CHOP, DHAP, DICE, IVAC, IMVP-16, and FND. RESULTS: Of the 35 patients, 30 received rituximab-combined regimens, and 5 received rituximab alone. A total of 102 cycles of rituximab-containing salvage regimens were administered. The objective response rate of the 32 evaluable cases was 68.8%, with a complete remission (CR) rate of 40.6%; 3 patients achieved CR after radiotherapy following rituximab-based regimens, and 3 achieved CR after autologous hematopoietic stem cell transplantation. The most frequent adverse events were nausea, leukopenia, and alopecia. The addition of rituximab to chemotherapy only elevated the occurrence of mild infusion-related reactions, such as chills, fever, and pruritus. The median follow-up time was 12.5 months (ranged from 3 to 69 months); 2 patients were lost, 10 were died (9 died of lymphoma, and 1 died of severe hepatitis), the other patients remained alive. The median progression-freely survival was 11.8 months (ranged from 3 to 33 months). The overall 1-, 2-, and 3-year survival rates were 72.9%, 62.8%, and 62.8%, respectively. CONCLUSION: Rituximab-containing salvage regimens are effective and well tolerated, even in extensively pretreated patients with relapsed or refractory B-cell NHL.

[Prognostic analysis of patients with nasal-type NK/T-cell non-Hodgkin's lymphoma--a report of 93 cases].

BACKGROUND & OBJECTIVE: Nasal-type NK/T-cell non-Hodgkin's lymphoma (NHL) is a unique subtype with the manifestation of local necrosis, infection and fever. The efficacy of chemotherapy alone is unsatisfactory; while radiochemotherapy plays some roles in the management of NK/T-cell lymphoma (NK/TCL). This study was to summarize the clinical characteristics, treatment outcome and prognosis of NK/TCL patients. METHODS: Records of 93 patients with NK/TCL from Jan. 1997 to Jun. 2004 were analyzed retrospectively. All the patients were classified according to WHO classification system. RESULTS: Of the 93 patients, 75 (80.6%) were in stage I-II, and 18 (19.4%) were in stage III-IV. The most common symptoms were nasal obstruction, rhinorrhea, and epistaxis. The disease course was 1-24 months with a median of 6.5 months. Of the 93 patients, 15 (16.1%) presented perforation of hard palate and/or nasal septum, 35 (37.6%) presented B symptoms; 35 (37.6%) were treated with chemotherapy alone, 2 (2.2%) were treated with radiotherapy alone, 54 (58.0%) were treated with radiochemotherapy, and 2 (2.2%) received no treatment. The first-line chemotherapy regimens were mainly CHOP and EPOCH. The overall response rate (RR) was 84.4% (76/90) with complete remission (CR) rate of 64.4% (58/90). The response rate of chemotherapy alone group was 67.6% (23/34) with CR rate of 41.2% (14/34). The response rate of combined modality group was 94.4% (51/54) with CR rate of 83.3% (45/54). The 2 patients who received no treatment died within 6 months. The major toxicity of chemotherapy was myelosuppression. The prevalence of grade III-IV neutropenia, thrombocytopenia, and anemia were 37.7%, 13.7%, and 10.7%. The major toxicities of radiotherapy were grade I-II mucosa lesion and myelosuppression. Other toxicities were mild. The mortality was 66.7% (62/93). The 1-, 3-, and 5-year overall survival (OS) rates were 63.4%, 43.1%, and 17.6%, respectively. Multivariate analysis showed that perforation of hard palate and/or nasal septum, B symptoms and therapeutic modality were independent prognostic factors of NK/TCL (P=0.035, P<0.001, and P=0.004). CONCLUSIONS: NK/TCL has low chemotherapy sensitivity. Although combined chemoradiotherapy yield better outcome, the long-term survival was still poor. Investigation of optional treatment is needed.

[Long-term outcomes of 392 non-Hodgkin's lymphoma patients treated with pirarubicin based regimens].

OBJECTIVE: To analyse the effectiveness and toxicity of combined chemotherapy regimen containing pirarubicin (THP) in the treatment of non-Hodgkin's lymphoma (NHL). METHODS: Three hundred and ninety two patients with NHL were treated by THP containing regimen with or without involved field radiotherapy. The clinical characteristics, response, toxicity and long-term survival rates were analysed. RESULTS: The median age of the patients was 47 (5 - 87) years and 26.0% aged more than 60 years. 61.0% of the patients were males and 39.0% females. B-cell and T/NK cell NHL accounted for 68.4% and 23.2% respectively with 56.9% of diffuse large B cell lymphoma and 12.5% of peripheral T cell lymphoma. 92.6% of the patients were ECOG < 1, 63.2% in stage I + II, 84.7% with IPI score 0 - 2 and 25% with B symptoms, 93.9% (368/392) of the patients received CTOP (containing THP) regimen chemotherapy and among them 28.5% (112/392) plus involved field radiotherapy. Altogether 1598 courses were administered on 368 patients. The overall response rate was 88.5% (341/385) with a complete remission (CR) rate of 63.6%, major toxicity was myelosuppression with 12.8%, 1.0% and 1.5% of grade III - IV neutropenia, thrombocytopenia and anemia, respectively. G-CSF support was given for 553 courses (34.6%). Alopecia account for 19.8%. The incidence of mild cardiotoxicity was 5.8%. Treatment-related mortality was 1.6% (6/368). Median follow-up was 24 months. The 1, 3 and 5 year actuarial survival rates were 86.4% , 66.5% and 59.2%, respectively. Median survival time has not been achieved. CONCLUSION: The efficacy of THP based regimen CTOP for the treatment of aggressive NHL is promising. Further clinical trial is warranted.

[Clinical outcomes of 106 patients with peripheral T-cell lymphoma treated by standard CHOP regimen].

BACKGROUND & OBJECTIVE: T-cell Non-Hodgkin's lymphoma (NHL) are common in Asia, It's biological behavior is different from B-cell NHL. It often shows lower chemo-sensitivity, high incidence of relapse and poor prognosis. This study was designed to analyse the clinical characteristics and to evaluate the effectiveness and toxicity of standard CHOP regimen in the treatment of peripheral T-cell lymphomas-unspecified (PTCL-U) according to the Revised European- American Lymphoma (REAL) classification. METHODS: 106 patients with PTCL-U were treated by standard CHOP regimen with or without involved field radiotherapy from January 1997 to December 2003 in Cancer Center, Sun Yat-sen University, The clinical characteristics, response and long-term survival rates were analysed, retrospectively. RESULTS: Early stages (I-II) were present in 78.3% (83/106) of the patients. Extranodal involvement account for 84.0% (89/106) with 34.9% (37/106) of more than 1 involved extranodal sites. The percentage of IPI score 0-1 was 78.3% (83/106). All the patients were treated by standard CHOP regimen plus IFRT for bulky disease. 55.7% (59/106) patients were treated by chemotherapy alone and 43.3% (46/106) were treated by chemotherapy plus radiotherapy. The overall response rate was 81.0% (85/105) with 58.2%(65/105) complete remission (CR) rates. The response rate of chemotherapy alone were 69.5% (41/59) and CR rates was 44.1% (26/59). The median duration of response was 16 months (1-88 months). The actual 1, 3 and 5 year overall survival rates were 69.9%, 42.9% and 22.0%, respectively. Median survival times were 24 (12-36) months. CONCLUSION: Long-term survival of PTCL-U treated by standard CHOP regimen were poor. Further investigation is wanted.