MYC-dependent MiR-7-5p regulated apoptosis and autophagy in diffuse large B cell lymphoma by targeting AMBRA1.

Diffuse large B-cell lymphoma (DLBCL) is the leading cause of mortality from invasive hematological malignancies worldwide. MicroRNA-7-5p (miR-7-5p) has been shown to be a tumor suppressor in several types of tumors. However, its role in DLBCL is not fully understood. This study explored the role of miR-7-5p in the progression of DLBCL and pursued the underlying mechanism. Quantitative real-time PCR and transfection of miRNA mimic and inhibitors were used to assess the effects of miR-7-5p on autophagy and apoptosis in SU-DHL-4 and SU-DHL-10 cells. Dual-luciferase reporter assay was used to identify target genes of miR-7-5p. Immunofluorescence, flow cytometry, and western blotting (WB) were performed to explore the underlying mechanism and downstream pathways of miR-7-5p and AMBRA1 in DLBCL cells. MiR-7-5p was upregulated in DLBCL cells. Luciferase reporter assays implicated AMBRA1 as a downstream target of miR-7-5p in DLBCL. WB and flow cytometry showed that an increase in miR-7-5p level and a decrease in AMBRA1 expression led to a decrease in autophagy and apoptosis-related protein expression. Furthermore, miR-7-5p prevented c-MYC dephosphorylation through AMBRA1 downregulation. On the contrary, c-MYC increased the expression of miR-7-5p, thereby establishing positive feedback on miR-7-5p transcription. The addition of hydroxychloroquine, an autophagy inhibitor, reduced autophagy and increased apoptosis in DLBCL cells. In vivo experiments further proved that the increase of miR-7-5p played a regulatory role in the expression of downstream AMBRA1 and c-MYC. These results demonstrate that c-MYC-dependent MiR-7-5p suppressed autophagy and apoptosis by targeting AMBRA1 in DLBCL cells. MiR-7-5p also suppressed autophagy and apoptosis by targeting AMBRA1 in DLBCL cells. Therefore, these data suggest that targeting miR-7-5p may be a promising strategy in DLBCL therapy.

Genomic features reveal potential benefit of adding anti-PD-1 immunotherapy to treat non-upper aerodigestive tract natural killer/T-cell lymphoma.

Natural killer/T-cell lymphoma (NKTCL) is a highly heterogeneous disease with a poor prognosis. However, the genomic characteristics and proper treatment strategies for non-upper aerodigestive tract NKTCL (NUAT-NKTCL), a rare subtype of NKTCL, remain largely unexplored. In this study, 1589 patients newly diagnosed with NKTCL at 14 hospitals were assessed, 196 (12.3%) of whom had NUAT-NKTCL with adverse clinical characteristics and an inferior prognosis. By using whole-genome sequencing (WGS) and whole-exome sequencing (WES) data, we found strikingly different mutation profiles between upper aerodigestive tract (UAT)- and NUAT-NKTCL patients, with the latter group exhibiting significantly higher genomic instability. In the NUAT-NKTCL cohort, 128 patients received frontline P-GEMOX chemotherapy, 37 of whom also received anti-PD-1 immunotherapy. The application of anti-PD-1 significantly improved progression-free survival (3-year PFS rate 53.9% versus 17.0%, P = 0.009) and overall survival (3-year OS rate 63.7% versus 29.2%, P = 0.01) in the matched NUAT-NKTCL cohort. WES revealed frequent mutations involving immune regulation and genomic instability in immunochemotherapy responders. Our study showed distinct clinical characteristics and mutational profiles in NUAT-NKTCL compared with UAT patients and suggested adding anti-PD-1 immunotherapy in front-line treatment of NUAT-NKTCL. Further studies are needed to validate the efficacy and related biomarkers for immunochemotherapy proposed in this study.

Onychopathy Following Durvalumab Treatment for Extensive-Stage Small-Cell Lung Cancer: A Case Report.

Patients treated with immune checkpoint inhibitors (ICIS) are prone to immune related adverse events (irAEs), making it important to pay attention to these adverse events. Herein, we report a case of onychopathy after treatment of extensive small cell lung cancer (ES-SCLC) with durvalumab; this is the first report of onychopathy caused by durvalumab in a patient with lung cancer. The change in the patient's nails mainly manifested in the form of pigmentation and the thickening of the nails. Antifungal ointment was ineffective, and these changes were unrelated to malnutrition or any other factors. In addition, this case shows that onychopathy may occur within 2 years after treatment, indicating that these patients need long-term follow-up.

Surgical therapy and survival in young patients with stage I-II hepatocellular carcinoma: a retrospective cohort study.

Background: Hepatocellular carcinoma (HCC) is regarded as a high-mortality cancer, but the effectiveness of surgical strategies for young patients with early-stage HCC remains controversial. We aimed to analyze the survival in young patients with stage I-II HCC who underwent different kinds of surgical treatments. Methods: Overall survival (OS) and cancer-specific survival (CSS) were compared among patients aged 18-45 years with stage I-II HCC from the Surveillance, Epidemiology, and End Results (SEER) database (2004-2013) who underwent local tumor destruction (LTD), wedge or segmental resection (WSR), lobectomy resection (LR), liver transplantation (LT), or non-surgery. Univariate and multivariate analyses and Kaplan-Meier method were used to examine the OS and CSS of the patients. A stratification analysis of CSS was also conducted among the subgroups. Results: Data from 664 patients were extracted. The median survival time was 46 months. In the multivariate analysis of OS, compared with non-surgery, LTD [hazard ratio (HR), 0.37; 95% confidence interval (CI): 0.25-0.54; P<0.0001], LR (HR, 0.29; 95% CI: 0.19-0.45; P<0.0001), and WSR (HR, 0.26; 95% CI: 0.17-0.39; P<0.0001) had better outcomes, and LT had the best survival benefit (HR, 0.24; 95% CI: 0.16-0.36; P<0.0001), which was similar to CSS. In the stratification analysis, compared with the non-surgery group, among patients with chemotherapy, LT reduced the risk of CSS by 64% (HR, 0.36; 95% CI: 0.19-0.66; P interaction=0.0004). Conclusions: Surgery offers a survival benefit compared with non-surgery for young patients with stage I-II HCC. LT is associated with better survival than WSR, LR, and LTD.

First-line treatments for patients with advanced ALK gene rearrangements in NSCLC: a systematic review and network meta-analysis.

OBJECTIVE: To conduct a network meta-analysis of randomised controlled trials to determine the optimal clinical choice of first-line therapy for patients with ALK receptor tyrosine kinase (ALK) gene rearrangement non-small cell lung cancer (NSCLC). METHODS: Clinical trials in patients with histologically confirmed ALK gene rearrangement NSCLC, that included ALK inhibitors as first-line therapy, were identified using database searches. A Bayesian network meta-analysis was conducted to calculate the efficacy and safety of the included first-line treatments. RESULTS: Nine trials with 2,407 patients were included for analyses. Lorlatinib was better than brigatinib for progression-free survival (PFS) (hazard ratio 0.79, 95% confidence interval 0.63, 0.98). In subgroup analyses, lorlatinib exhibited the highest probability of best PFS ranking in patients with or without baseline brain metastases (38% and 80%, respectively); brigatinib had the highest probability of best PFS ranking among Asian patients (47%). Alectinib offered the highest survival advantage (57% probability), while lorlatinib was likely to be the best treatment for an objective response (41% probability). Alectinib displayed the highest probability of being ranked lowest for grade ≥3 adverse events (86%). CONCLUSIONS: Lorlatinib was associated with the best PFS overall, and was suitable for patients with or without brain metastases. Brigatinib was associated with the best PFS in Asian patients.

The impact of surgery on long-term survival of patients with primary intestinal non-Hodgkin lymphomas based on SEER database.

Evidence regarding the need for surgery for primary intestinal non-Hodgkin lymphoma (PINHL) patients with chemotherapy is limited and controversial. We aimed to investigate the specific impact of surgery on survival of PINHL patients. Data from PINHL patients (aged > 18 years) with chemotherapy between 1983 and 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We concerned about overall survival (OS) and improved cancer-specific survival (CSS). Propensity score matching (PSM) analysis was also used to explore the reliability of the results to further control for confounding factors. Finally, we screened 3537 patients. Multivariate regression analysis showed that patients with surgery and chemotherapy had better OS (hazard ratio [HR] 0.83; 95% confidence interval [CI] 0.75-0.93; p = 0.0009) and CSS (HR 0.87; 95% CI 0.77-0.99; p = 0.0404) compared with the non-operation group after adjusting for confounding factors. After PSM analysis, compared with non-surgery, surgery remained associated with improved OS (HR 0.77; 95% CI 0.68-0.87; p < 0.0001) and improved CSS (HR 0.82; 95% CI 0.72-0.95; p = 0.008) adjusted for baseline differences. In the large cohort of PINHL patients with chemotherapy older than 18 years, surgery was associated with significantly improved OS and CSS before and after PSM analysis.

Functional drug-target-disease network analysis of gene-phenotype connectivity for curcumin in hepatocellular carcinoma.

BACKGROUND: The anti-tumor properties of curcumin have been demonstrated for many types of cancer. However, a systematic functional and biological analysis of its target proteins has yet to be fully documented. The aim of this study was to explore the underlying mechanisms of curcumin and broaden the perspective of targeted therapies. METHODS: Direct protein targets (DPTs) of curcumin were searched in the DrugBank database. Using the STRING database, the interactions between curcumin and DPTs and indirect protein targets (IPTs) weres documented. The protein-protein interaction (PPI) network of curcumin-mediated proteins was visualized using Cytoscape. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis was performed for all curcumin-mediated proteins. Furthermore, the cancer targets were searched in the Comparative Toxicogenomics Database (CTD). The overlapping targets were studied using Kaplan-Meier analysis to evaluate cancer survival. Further genomic analysis of overlapping genes was conducted using the cBioPortal database. Lastly, MTT, quantitative polymerase chain reaction (qPCR), and western blot (WB) analysis were used to validate the predicted results on hepatocellular carcinoma (HCC) cells. RESULTS: A total of five DPTs and 199 IPTs were found. These protein targets were found in 121 molecular pathways analyzed via KEGG enrichment. Based on the anti-tumor properties of curcumin, two pathways were selected, including pathways in cancer (36 genes) and HCC (22 genes). Overlapping with 505 HCC-related gene sets identified in CTD, five genes (TP53, RB1, TGFB1, GSTP1, and GSTM1) were finally identified. High mRNA levels of TP53, RB1, and GSTM1 indicated a prolonged overall survival (OS) in HCC, whereas elevated mRNA levels of TGFB1 were correlated with poor prognosis. The viability of both HepG2 cells and Hep3B cells was significantly reduced by curcumin at concentrations of 20 or 30 µM after 48 or 72 h of culture. At a concentration of 20 µM curcumin cultured for 48 h, the expression of TGFB1 and GSTP1 in Hep3B cells was reduced significantly in qPCR analysis, and reduced TGFB1 protein expression was also found in Hep3B cells.

Coexisting of myasthenia gravis and fulminant myocarditis induced by nivolumab in a patient with ureteral epithelial cancer.

The adverse events of immune checkpoint inhibitors (ICIs) are mostly immune mediated reactions. In this study, we presented a patient who developed coexisting of myasthenia gravis, myocarditis and anemia after treatment with nivolumab only 1 cycle for ureteral epithelial cancer. A 66-year-old woman was admitted to our department with the complaint of recurrent hematuria and backache for 2 months. This patient was diagnosed with stage IV, T4N3M1, urothelial carcinoma of the right kidney. She received immune checkpoint therapy consisting of nivolumab. Then, the physical and neurological examination found the ptosis of eyes especially the right eye and weakness of proximal limb muscles. Patient presented with sub-sternal chest discomfort, shortness of breath, electrocardiograms suggested atrial fibrillation and possible acute myocardial ischemic. One week later, this patient died of ventricular arrhythmia. This patient has increased clinical awareness by indicating that the immune-related adverse events (irAEs) could simultaneously involve multiple systems and progress quickly. Early recognition of aberrant immune activation and complete evaluation upon the occurrence of irAEs are critical.

Analysis of Molecular Mechanism of YiqiChutan Formula Regulating DLL4-Notch Signaling to Inhibit Angiogenesis in Lung Cancer.

In order to explore the specific mechanism of YiqiChutan formula (YQCTF) in inhibiting the angiogenesis of lung cancer and its relationship with delta-like ligand 4- (DLL4-) Notch signaling, 30 healthy BALB/c-nu/nu rats were selected and divided into three groups: A549 group (implanted with lung adenocarcinoma cell line A549), NCI-H460 group (implanted with human lung large-cell carcinoma cell line NCI-H460), and NCI-H446 group (implanted with human lung small cell carcinoma cell line NCI-H446) for constructing lung cancer transplanted tumor models. After modeling, the group treated with normal saline was taken as control group, 200 mg/kg of YQCTF was adopted for intervention, and the tumor volume and growth inhibition rate were compared with the vascular targeted inhibitor Sorafenib. HE staining, CD31 fluorescent antibody staining, and microelectron microscopy were adopted to observe the neovascular endothelial cells of the transplanted tumor. The expression of VEGF, HIF-1α, DLL4, and Notch-1 in the transplanted tumors in each group was detected by Western blot and RT-PCR at the protein level or mRNA level. Compared with the control group, the YQCTF-treated group had obvious inhibitory effect on lung cancer transplanted tumor and lung cancer angiogenesis. In the YQCTF-treated group, the density of angiogenesis decreased significantly and the vascular lumen structure also decreased, and the expression levels of VEGF, HIF-1α, DLL4, and Notch-1 in the YQCTF-treated group were all lower than those in the control group. YQCTF could inhibit the growth of lung cancer transplanted tumor through antiangiogenesis, and it could also reduce the amount of angiogenesis in lung cancer transplanted tumor. In addition, the generation of lumen structure was also hindered, which was realized through the VEGF signaling pathway and DLL4-Notch signaling pathway.

Development and External Validation of a Nomogram to Predict Cancer-Specific Survival in Patients with Primary Intestinal Non-Hodgkin Lymphomas.

PURPOSE: Primary intestinal non-Hodgkin lymphoma (PINHL) is a biologically and clinically heterogeneous disease. Few individual prediction models are available to establish prognoses for PINHL patients. Herein, a novel nomogram was developed and verified to predict long-term cancer-specific survival (CSS) rates in PINHL patients, and a convenient online risk calculator was created using the nomogram. MATERIALS AND METHODS: Data on PINHL patients from January 1, 2004, to December 31, 2015, obtained from the Surveillance, Epidemiology, and End Results (SEER) database (n = 2372; training cohort), were analyzed by Cox regression to identify independent prognostic parameters for CSS. The nomogram was internally and externally validated in a SEER cohort (n = 1014) and a First Affiliated Hospital of Guangzhou University of Chinese Medicine (FAHGUCM) cohort (n = 37), respectively. Area under the receiver operating characteristic curve (AUC), calibration curves, and decision curve analysis (DCA) were used to evaluate nomogram performance. RESULTS: Five independent predictors were identified, namely, age, marital status, Ann Arbor Stage, B symptoms, and histologic type. The nomogram showed good performance in discrimination and calibration, with C-indices of 0.772 (95% CI: 0.754-0.790), 0.763 (95% CI: 0.734-0.792), and 0.851 (95% CI: 0.755-0.947) in the training, internal validation, and external validation cohorts, respectively. The calibration curve indicated that the nomogram was accurate, and DCA showed that the nomogram had a high clinical application value. AUC values indicated that the prediction accuracy of the nomogram was higher than that of Ann Arbor Stage (training cohort: 0.804 vs 0.630; internal validation cohort: 0.800 vs 0.637; external validation cohort: 0.811 vs 0.598), and Kaplan-Meier curves indicated the same. CONCLUSION: A nomogram was developed to assist clinicians in predicting the survival of PINHL patients and in making optimal treatment decisions. An online calculator based on the nomogram was made available at https://cuifenzhang.shinyapps.io/DynNomapp/.

mRNA expression profile analysis reveals a C-MYC/miR-34a pathway involved in the apoptosis of diffuse large B-cell lymphoma cells induced by Yiqichutan treatment.

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of adult non-Hodgkin's lymphoma (NHL). While DLBCL is sensitive to chemotherapy, a certain percentage of patients with DLBCL experience relapse. Previous studies have indicated that Yiqichutan treatment, which was developed to treat NHL, can inhibit DLBCL cell growth, but the mechanism is not fully understood. The present study identified 991 differentially expressed mRNAs, with 498 upregulated and 493 downregulated (P<0.05), in SUDHL-6 cells exposed to Yiqichutan. The underlying pathways included the Jak/Stat and PI3K signaling pathways. In total, six representative mRNAs were selected for validation with reverse transcription-quantitative PCR (RT-qPCR), and a strong correlation was identified between the RT-qPCR results and microarray data. Since the transcription factor C-MYC is involved in both the Jak/Stat and PI3K signaling pathways, C-MYC and its associated microRNA (miR) were selected for further analysis. It was found that knockdown of C-MYC increased miR-34a expression levels, inhibited forkhead box P1 (Foxp1) expression levels and promoted DLBCL cell apoptosis. In addition, the miR-34a mimics further enhanced the role of C-MYC knockdown. It was demonstrated that, the expression levels of apoptotic factors Bax and poly (ADP-ribose) polymerase were significantly upregulated with C-MYC knockdown and miR-34a mimics in SUDHL-6 cells, while the Bcl2 expression level was significantly reduced. Moreover, Yiqichutan treatment increased miR-34a expression levels and induced apoptosis, as well as reducing Foxp1 expression level in SUDHL-6 cells. Therefore, the present results suggested that Yiqichutan treatment affected DLBCL cells via several signaling pathways. Furthermore, Yiqichutan may inhibit the proliferation of DLBCL cells by blocking the C-MYC/miR-34a signaling pathway.

The Efficacy and Toxicity of Lobaplatin-contained Chemotherapy in Extensive-stage Small-cell Lung Cancer.

To assess the efficacy and toxicity of Lobaplatin (LBP) -contained chemotherapy on extensive stage small-cell lung cancer (ES-SCLC), we conducted a prospective, single-arm, and multicenter Phase IV clinical trial on Lobaplatin (ChiCTR-ONC-13003471), and used the patient clinical data obtained from our cancer center to perform the analysis. Previously untreated patients with ES-SCLC were given LBP intravenously (IV) at 30 mg/m2 on day 1 and etoposide IV at 100 mg/m2 on day 1, 2, and 3. The treatment was cycled every 21 days, lasting for four to six cycles. The patients with second-line treatment or above were also included in the study, and they were treated with LBP-contained regimen: a single dose of LBP at 50 mg/m2 on day 1 through IV; combined application, LBP30 mg/m2 IV on day 1. From May 2015 to August 2016, 36 patients were enrolled in the study at our cancer center. For the 30 first-line patients, the median overall survival (OS) and the median progression-free survival (PFS) was 13.0 months (ranging from 11.2 to 14.7 months) and 4.7 months (ranging from 1.6 to 7.7 months) respectively, with overall response rate of 57 % and disease control rate of 85.7%. For the 6 patients with second-line treatment or above, one patient got a partial response (PR) and four patients got a stable disease (SD). The most frequent drug-related adverse effects were leukopenia and neutropenia, and no grade 3/4 hepatotoxicity or nephrotoxicity was observed. These results indicated that LBP-contained chemotherapy was effective and tolerable for extensive stage SCLC in terms of response and survival. However, due to the small sample size of this study, we need to wait for the OS data of phase Ⅲ clinical trial and the final data of this multicenter Phase IV study to draw the conclusion.

Late distant recurrence of breast carcinoma and metastasis to the main bronchus and choroid: A case report.

RATIONALE: Metastases of breast carcinoma to the main bronchus and choroid are rare, but have been reported in relevant literature. Late distant recurrence of breast carcinoma after more than 20 years is extremely rare. Herein, we report a 57-year-old woman with late distant recurrence and metastasis to the main bronchus and choroid almost 28 years after surgery. PATIENT CONCERNS: At the age of 29, the patient underwent chemotherapy and endocrine treatment after a right side mastectomy to remove breast carcinoma. The patient was hospitalized for a cough with blood-tinged sputum, dysphagia, and blurred vision in the left eye at the age of 57. DIAGNOSES: On evaluation, laboratory findings detected the elevated serum tumor markers of CA12-5, CA15-3, NSE, and Cyfra21-1. The imaging showed left lung metastase, multiple lymph node metastases, and small suspected metastases in the both sides of parietal lobes. Fundus fluorescein angiography showed choroidal occupying lesion of the left side which indicates secondary metastasis and retinal detachment. Combined with the pathological finding via fiberoptic bronchoscopic biopsy, the patient was clinically diagnosed with a late distant recurrence of breast carcinoma. INTERVENTIONS: The patient received oral endocrine therapy of letrozole, but she refused chemotherapy, radiotherapy and other topical treatments. OUTCOMES: At the 3-month follow-up visit, the multiple lesions of the left lung and lymph nodes had partially regressed, and the lesion of right parietal lobe had disappeared. The patient's clinical symptoms, such as blood-tinged sputum and dysphagia, had significantly improved. LESSONS: We have described this case and reviewed the relevant literature concerning late distant recurrence of breast carcinoma. Importantly, this case indicates that patients with HR positive breast carcinoma are more likely to develop late distant recurrence and clinicians should not ignore the follow-up examinations even more than 20 years after the surgery.

Java brucea and Chinese herbal medicine for the treatment of cholesterol granuloma in the suprasellar and sellar regions: A case report and literature review.

RATIONALE: A cholesterol granuloma (CG) is usually found in the middle ear, papilla, orbits, petrous apex, and choroid plexus, but is highly uncommon in the skull. In spite of benign clinicopathological lesions, bone erosion can be seen occasionally in the patient with CG. The optimal treatment strategy is radical surgery, but complete excision is usually impossible due to anatomical restrictions and a risk of injury to the key structures located nearby. Here, we report a patient with CGs in the suprasellar and sellar regions who was successfully treated with Java brucea and Chinese herbal medicine. PATIENT CONCERNS: A 31-year-old man presenting with progressive decreased vision in both eyes was analyzed. DIAGNOSES: A skull magnetic resonance imaging (MRI) scan showed a low-density tumor in the uprasellar and sellar regions and histopathological examination revealed a CG. INTERVENTIONS: The patient was referred the surgery and radiotherapy. In the meantime, brucea soft capsules and herbal medicine combined were administered to him. OUTCOMES: The related clinical symptoms and signs resolved significantly after several months, as his therapy progressed. The patient showed no sign of recurrence during the treatment period. Furthermore, he was still alive and disease-free at 37 months of follow-up visit. LESSONS: Overall, brucea soft capsules and a Chinese herbal formula treatment combined could be beneficial in improving the patient's quality of life with CG in the skull.

Chemotherapy Near the End of Life for Chinese Patients with Solid Malignancies.

INTRODUCTION: There are increasing concerns about the negative impacts of chemotherapy near the end of life (EOL). There is discrepancy among different countries about its use, and little is known about the real-world situation in China. PATIENTS AND METHODS: This retrospective study was conducted at six representative hospitals across China. Adult decedents with a record of advanced solid cancer and palliative chemotherapy were consecutively screened from 2010 through 2014. The prevalence of EOL chemotherapy within the last 1 month of life was set as the primary outcome. The correlations among EOL chemotherapy, clinicopathological features, and overall survival (OS) were investigated. RESULTS: A total of 3,350 decedents who had had cancer were consecutively included; 2,098 (62.6%) were male and the median age was 56 years (range, 20-88). There were 177 (5.3%), 387 (11.6%), and 837 (25.0%) patients who received EOL chemotherapy within the last 2 weeks, 1 month, and 2 months of life, respectively. We identified inferior OS (median OS, 7.1 vs. 14.2 months; hazard ratio, 1.37; 95% confidence interval [CI], 1.23-1.53; p < .001), more intensive treatments (e.g., admitted to intensive care unit [ICU] in the last month of life, received cardiopulmonary resuscitation and invasive ventilation support), and hospital death (odds ratio, 1.53; 95% CI, 1.14-2.06; p = .005) among patients who received continued chemotherapy within the last month compared with those who did not. However, subgroup analyses indicated that receiving oral agents correlated with fewer ICU admissions and lower rates of in-hospital death. CONCLUSION: This study showed that EOL chemotherapy is commonly used in China. Intravenous chemotherapy at the EOL significantly correlated with poor outcomes and the role of oral anticancer agents warrants further investigation. The Oncologist 2017;22:53-60Implications for Practice: The role of chemotherapy toward the end of life (EOL) in patients with solid cancers is debatable. This article is believed to be the first to report the current prevalence of EOL chemotherapy in China. This study found that, compared with oral anticancer agents, intravenous chemotherapy at the EOL was significantly associated with poor outcomes. Therefore, the role of oral anticancer agents at the EOL stage deserves further investigation.

Detection of the value of consecutive serum total light chain (sTLC) in patients diagnosed with diffuse large B cell lymphoma.

There are limited data on serum total light chain (sTLC) in lymphoma and its relative role on the outcome of diffuse large B cell lymphoma (DLBCL) patients. Blood samples from 46 cases newly diagnosed with DLBCL were collected consecutively during chemotherapy to detect sTLC, IgG, IgA, and IgM levels. Clinical data and survival outcomes were analyzed according to the results of sTLC measurements. In summary, 22 patients (47.8 %) had abnormal k or λ light chain, respectively, and 6 patients (13.0 %) had both abnormal k and λ light chains before chemotherapy. Patients with elevated k light chain more frequently displayed multiple extra-nodal organ involvement (P = 0.01) and had an inferior overall survival (OS) (P = 0.041) and progression-free survival (PFS) (P = 0.044) compared to patients with normal level of k light chain. Furthermore, patients with elevated level of both k and λ also exhibited significant association with shorter OS (P = 0.002) and PFS (P = 0.009). Both elevated k alone and concurrent elevated k and λ had independent adverse effects on PFS (P = 0.031 and P = 0.019, respectively). sTLC level was reduced gradually by treatment in this study and reached the lowest point after the fourth cycle of chemotherapy, which was consistent with the disease behavior during chemotherapy. Considering the small sample size of this study, these results should be confirmed in a larger prospective study.

Non-Hodgkin's lymphoma involving the ileocecal region: a single-institution analysis of 46 cases in a Chinese population.

BACKGROUND AND GOALS: Non-Hodgkin's lymphoma (NHL) involving the ileocecal region is a rare occurrence. Optimal management and treatment outcomes of ileocecal NHL have not been well defined. STUDY: In this study, clinical characteristics, treatment outcomes, and prognostic factors of 46 Chinese patients with ileocecal NHL were retrospectively analyzed. RESULTS: Among 46 patients, the median age of these patients was 46 years and 84.8% of them were male. Twenty-four cases (52.2%) had early-stage disease (stage I/II1/II2) and 35 (76.1%) cases were of B-cell origin. Higher incidence of fever (P=0.001) and intestinal perforation (P=0.038) at onset was observed in T-cell lymphomas. Surgical emergencies occurred in 13 patients, including 8 patients who were receiving chemotherapy. Patients with T-cell advanced ileocecal NHL (stage IIE/IV) suffered more surgical emergencies during chemotherapy than others (P=0.005). The 5-year overall survival and progression-free survival rates for these 46 patients were 64.2% and 49.3%, respectively. Early-stage cases undergoing radical resection before chemotherapy had a prolonged 5-year progression-free survival rate (P=0.01). In multivariate analysis, both advanced stage and T-cell phenotype were identified as independent prognostic factors for poor survival. CONCLUSIONS: Radical resection before chemotherapy should be considered in early-stage ileocecal NHL to achieve a better survival. Palliative resection of the primary lesion before chemotherapy may be necessary in T-cell advanced cases to avoid surgical emergencies during chemotherapy. Owing to the small sample number in this study, a prospective analysis with larger sample number is highly necessary.

Expression of PIK3CA and FOXP1 in gastric and intestinal non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue type.

Non-Hodgkin's lymphoma of mucosa-associated lymphoid tissue (MALT) type arises from a wide variety of extranodal sites, most frequently from the gastrointestinal tract. Recently, it has been demonstrated that karyotypic alterations involving the PIK3CA and FOXP1 genes of chromosome 3 occur in MALT lymphoma. However, their associated protein expression has not been extensively studied. Tumor tissues from 27 gastric and 23 intestinal MALT lymphomas were analyzed for PIK3CA and FOXP1 protein expression using immunohistochemistry and correlated with histological features and treatment outcomes. Expression of PIK3CA, a novel indicator, was found in 40% of gastrointestinal cases and indicated an inferior progression-free survival in both gastric and intestinal MALT lymphomas (P = 0.001 and P = 0.015). Tumor staining of nuclear FOXP1 (46.0%) was more common in gastric than intestinal MALT lymphomas (P = 0.042) and was significantly associated with polymorphic histology (P = 0.007). FOXP1 expression was identified as an adverse prognostic factor for overall survival in gastric MALT lymphomas (P = 0.035). We further combined these two markers and observed that patients that are positive for both PIK3CA and FOXP1 had a worse overall and progression-free survival. Considering the small sample size of this study, these results should be confirmed in a large prospective study.

Long-term results of pirarubicin versus doxorubicin in combination chemotherapy for aggressive non-Hodgkin's lymphoma: single center, 15-year experience.

Pirarubicin is an analog of doxorubicin. Few studies have compared the long-term outcomes of patients receiving pirarubicin-based THP-COP and doxorubicin-based CHOP in the treatment of non-Hodgkin's lymphoma (NHL). We retrospectively compared the efficacy and safety of these two regimens in 459 previously untreated aggressive NHL patients admitted to Sun Yat-Sen University Cancer Center from 1987 to 2003. For initial treatment, 205 patients received the THP-COP regimen, and 254 patients received the CHOP regimen. The patients' characteristics were well balanced. The groups did not differ in the complete remission rate (THP-COP, 57.1% vs. CHOP, 57.0%; P = 0.998) or response rate (THP-COP, 82.9% vs. CHOP, 81.5%; P = 0.691). At a median follow-up of 95.7 months, the 8-year survival rates were also similar (overall survival: THP-COP, 55.8% vs. CHOP, 56.7%; progression-free survival: THP-COP, 47.3% vs. CHOP, 43.5%; lymphoma-specific survival: THP-COP, 51.2% vs. CHOP, 48.5%). The THP-COP group had fewer cases of alopecia (P < 0.001) and gastrointestinal toxicities (P = 0.015). A tendency toward decreased arrhythmia (P = 0.075), especially in elderly patients (P = 0.030), was found. In combination chemotherapy for aggressive NHL, pirarubicin has comparable efficacy to doxorubicin and has a lower incidence of alopecia, gastrointestinal toxicities, and arrhythmia. Further studies are warranted to confirm these results.