Clinical analysis of patients with primary and secondary extranodal natural killer/T-cell lymphoma of central nervous system.

Extranodal natural killer (NK)/T-cell lymphoma (NKTL) is a rare non-Hodgkin lymphoma that rarely arise exclusively in or metastasizes to the central nervous system (CNS). Globally, CNS involvement of NKTL heralds a serious prognosis and there is no standard treatment. 19 of 414 patients (4.59%) with ENKL followed were diagnosed with CNS involvement between 2006 and 2020. Two patients had primary CNS (PCNS) NKTL, and 17 patients had secondary CNS (SCNS) invasion. A total of 9 patients survived and 10 patients died. The median overall survival time was 55 months, and the median survival time after CNS invasion was 17 months. The 5-year cumulative survival probability was 45.7%. In conclusion, CNS risk evaluation and prophylaxis treatment can be carried out for patients with NK/T-cell lymphoma prognostic index risk group III/IV. In terms of treatment, systemic therapy based on methotrexate combined with radiotherapy and intrathecal chemotherapy can be selected.

Orelabrutinib-bruton tyrosine kinase inhibitor-based regimens in the treatment of central nervous system lymphoma: a retrospective study.

BACKGROUND: Central nervous system lymphoma (CNSL) is an aggressive lymphoma. Orelabrutinib, an oral Bruton tyrosine kinase inhibitor, is a new treatment strategy for CNSL. This study aims to evaluate the efficacy and safety of orelabrutinib-based regimens in the treatment of patients with CNSL. METHODS: Twenty-three patients with CNSL were included in this retrospective study. All patients received the orelabrutinib-based regimen. Efficacy was evaluated based on investigators' assessment of overall response rate (ORR), complete response/unconfirmed complete response (CR/CRu), partial response (PR), stable disease (SD), progressive disease (PD), duration of response (DOR), progression-free survival (PFS) and overall survival (OS). The safety of orelabrutinib-based regimens has also been evaluated. RESULTS: A total of 17.39% of patients received orelabrutinib-based regimens for consolidation therapy, and 82.61% of patients for induction therapy (4 newly diagnosed CNSL, 15 relapsed/refractory CNSL). In the newly diagnosed CNSL group, the ORR was 100% (1 CR, 1 CRu, 2 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 100%, 100%, and 100%, respectively. Of the 15 relapsed/refractory CNSL patients, five therapy regimens were applied (orelabrutinib, n = 3; orelabrutinib/immunotherapy, n = 3; orelabrutinib/chemotherapy, n = 2; orelabrutinib/immunochemotherapy, n = 6; orelabrutinib/radiotherapy, n = 1). The ORR was 60.00% (4 CR, 5 PR). The 6-month DOR rate, 6-month PFS rate, and 6-month OS rate were 92.30%, 67.70%, and 70.00%, respectively. Twenty-one patients reported adverse events (AEs), and 6 patients experienced grade ≥ 3 AEs. CONCLUSION: Orelabrutinib-based regimens were efficacious and well-tolerated in patients with CNSL. These combined therapies offer a new potential therapeutic strategy for patients with CNSL.

Radiotherapy vs sequential pegaspargase, gemcitabine, cisplatin and dexamethasone and radiotherapy in newly diagnosed early natural killer/T-cell lymphoma: A randomized, controlled, open-label, multicenter study.

To compare the efficacy and safety of radiotherapy (RT) and chemotherapy of pegaspargase, gemcitabine, cisplatin and dexamethasone (DDGP) combined with RT in newly diagnosed stage I-II natural killer/T-cell lymphoma (NKTL), we designed a randomized, controlled, open-label, multicenter clinical trial. Data from 65 stage I-II NKTL patients whose diagnoses were confirmed using immunohistochemistry were enrolled from January 2011 to December 2013 in the First Affiliated Hospital of Zhengzhou University. Patients were randomly divided into the RT group (n = 35) and the DDGP combined with RT group (n = 30). There was a difference between the Eastern Cooperative Oncology Group (ECOG) score in the two arms (P = .013). The complete response rate (CRR) and objective response rate (ORR) of DDGP combined with RT group were superior to those in the RT group (CRR: 73.3% vs 48.6%; ORR: 83.3% vs 60.0%, respectively). The 5-year progression-free survival (PFS) rate and overall survival (OS) rate in the DDGP combined with RT group were higher than those in the RT group (82.9% vs 56.5% for PFS, P = .023; 85.7% vs 60.4% for OS, P = .040), and treatment methods and lactate dehydrogenase were independent risk factors. Myelosuppression (P < .001), gastrointestinal reactions (P < .001), abnormal liver function (P = .007), coagulation abnormalities (P < .001) and baldness (P < .001) were more likely to occur in the DDGP combined with RT group. In conclusion, DDGP combined with radiotherapy obviously obtained great efficacy and prolonged the survival time of patients, also the side effects were mild for stage I-II NKTL. This trial was registered at https://register.clinicaltrials.gov as #NCT01501136.

Ibrutinib combined with venetoclax for the treatment of relapsed/refractory diffuse large B cell lymphoma.

Treatment outcomes of relapsed/refractory diffuse large B cell lymphoma (R/R DLBCL) are far from satisfactory. Certain efficacy of ibrutinib has been observed in non-GCB subtype DLBCL patients. This study aimed to investigate the efficacy and safety of ibrutinib plus BCL2 inhibitor venetoclax in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression. Combinational therapy (ibrutinib 560mg/day; venetoclax started 1 week later, oral dose increased from 100 to 400mg/day in 3 weeks) was conducted, and one cycle was 4 weeks. Both drugs were stopped when disease progress or serious adverse reactions appear. The primary end-point was overall response rate (ORR) at two cycles. From December 2018 to July 2020, a total of 13 patients were treated with the combined therapy. Among them, eleven (84.6%) patients previously received at least two treatment regimens, eight (61.5%) patients were C-myc and BCL2 double expression. The ORR at two cycles was 61.5%, with 3 (23.1%) patients achieved complete remission (CR) and 5 (38.4%) patients achieved partial remission (PR). The ORR at four cycles and six cycles was 53.8% and 46.2%, respectively. The median duration of response was 11 months (range, 1.5-13.6 months). The median progression-free survival and overall survival were 5.6 months (range, 0.4-15.6) and 11.3 months (range, 2.8-17.2), respectively. The most common adverse event was grade 1/2 neutropenia (53.8%), and nonhematologic toxicities included Grade1/2 diarrhea (46.2%) and elevated liver enzymes (30.8%). Combined therapy of ibrutinib and venetoclax showed promising efficacy and synergistic effects in R/R DLBCL patients with non-GCB subtype and BCL2 overexpression, and the toxicities were well-tolerated.

c-Myc mediated upregulation of long noncoding RNA SNHG12 regulates proliferation and drug sensitivity in natural killer/T-cell lymphoma.

Nasal-type natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy with poor outcomes. The treatment of NKTCL requires intensive chemotherapy. Long noncoding RNAs (lncRNAs) have been implicated in many cancers, including NKTCL. The elucidation of the multidrug resistance (MDR) may greatly contribute to explore novel therapeutic strategies. Herein, we explored the roles and potential regulatory mechanism of lncRNAs small nucleolar RNA host gene 12 (SNHG12) in MDR of NKTCL. We found that SNHG12 was upregulated in NKTCL tissue sections, and its high expression was positively correlated with clinical grade of malignancy of NKTCL. c-Myc and SNHG12 expression was upregulated in NKTCL cell lines. c-Myc- and SNHG12 overexpression promoted proliferation and inhibited sensitivity to cisplatin (CDDP) in NK/T-cell lymphoma cell line YTS cells, and c-Myc and SNHG12-downregulation inhibited proliferation and enhanced sensitivity to CDDP in SNK-6 cells. Moreover, c-Myc- and SNHG12 overexpression increased Ki67 and P-gp expression in YTS cells, whereas c-Myc and SNHG12-downregulation reduced the Ki67 and P-gp expression in SNK-6 cells. Correlational analyses revealed that c-Myc expression was positively correlated with SNHG12 expression in NKTCL tissues. Mechanism research showed that SNHG12 was a direct transcriptional target of c-Myc and c-Myc promoted SNHG12 expression in NKTCL cell lines. Further research showed that SNHG12 overexpression reversed the effects of c-Myc downregulation on proliferation and sensitivity to CDDP in NKTCL cell lines. Taken together, our findings first report that c-Myc mediated upregulation of SNHG12 promotes proliferation and inhibits drug sensitivity in NKTCL, which provides new insights into the therapeutic target for NKTCL.

Complete Blood Count Score Model Integrating Reduced Lymphocyte-Monocyte Ratio, Elevated Neutrophil-Lymphocyte Ratio, and Elevated Platelet-Lymphocyte Ratio Predicts Inferior Clinical Outcomes in Adult T-Lymphoblastic Lymphoma.

BACKGROUND: T-lymphoblastic lymphoma (T-LBL) is a highly aggressive neoplasm of lymphoblasts of T-cell origin. Although promising improvements have been recently achieved, one third of patients experience relapse or refractory T-LBL. Therefore, optimal strategies for identifying high-risk patients are urgently needed. MATERIALS AND METHODS: In the present study, 75 newly diagnosed adult patients (aged ≥15 years) with T-LBL were identified and the predictive value of complete blood count (CBC) abnormalities, including lymphocyte-monocyte ratio (LMR), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) on clinical outcomes, was analyzed. RESULTS: Using the receiver operating characteristic curve to determine the best cutoff values based on survival, it was found that patients with T-LBL with LMR ≤2.8, NLR ≥3.3, and PLR ≥200 had both inferior progression-free survival (PFS) and inferior overall survival (OS), in which the differences were much more remarkable in the international prognostic index score 0-2 subgroup. In the multivariable analysis, NLR ≥3.3 together with age >40 years and central nervous system (CNS) involvement were identified to be independently associated with shortened PFS, whereas PLR ≥200 and CNS involvement were identified to be independent risk factors for OS. LMR, NLR, and PLR were integrated to generate a "CBC score" model, which well separated adult patients with T-LBL into three risk groups, and the 3-year OS was 84%, 53%, and 30% for low-, intermediate-, and high-risk patients, respectively. CONCLUSION: Overall, a "CBC score" model was initially promoted for stratification in adult patients with T-LBL using simple, widely available, and easy to interpret parameters in the largest adult T-LBL cohort to date. IMPLICATIONS FOR PRACTICE: Optimal strategies for identifying high-risk patients with T-lymphoblastic lymphoma (T-LBL) are urgently needed. In the largest adult T-LBL cohort to date, simple, inexpensive, widely available parameters were applied and revealed that patients with lymphocyte-monocyte ratio (LMR) ≤2.8, neutrophil-lymphocyte ratio (NLR) ≥3.3, and platelet-lymphocyte ratio (PLR) ≥200 had both inferior progression-free survival and inferior overall survival (OS), in which the differences were much more remarkable in the international prognostic index score 0-2 subgroup. LMR, NLR, and PLR were integrated to generate a "complete blood count score" model, in which the 3-year OS was 84%, 53%, and 30% for low-, intermediate-, and high-risk patients, respectively.

SPARC is down-regulated by DNA methylation and functions as a tumor suppressor in T-cell lymphoma.

The aim of this study was to assess the functional role of SPARC in T-cell non-Hodgkin's lymphoma (T-NHL), as well as the underlying molecular mechanisms. Here, we first identified SPARC expression in T-NHL tissues and cell lines through western blot and real-time PCR (RT-PCR). Overall survival of T-NHL patients with different levels of SPARC was assessed by Kaplan-Meier survival curves. Then cell proliferation, apoptosis, migration and invasion of T-NHL cells with either knockdown or overexpression of SPARC were determined by MTT, flow cytometry, transwell migration and invasion assay, respectively. Finally, the molecular mechanism by which SPARC modulated T-NHL cell progression was assessed. We confirmed that SPARC was significantly down-regulated in T-NHL tissues and cell lines. T-NHL patients with high levels of SPARC demonstrated a favorable clinical outcome. SPARC significantly suppressed cell proliferation, migration and invasion, and EMT process, but facilitated cell apoptosis in T-NHL cells. Further, we found that loss of SPARC expression in T-NHL tissues and cell lines, both in mRNA and protein levels, was associated with the aberrant DNA methylation in SPRAC gene, and the disrupted SPARC expression could be rescued after treatment with the demethylating agent 5-Aza-2'-deoxycitydine (5-Aza-Cdr). Additionally, 5-Aza-Cdr reversed SPARC hypermethylation to restore its biological role as a tumor suppressor in T-NHL cells, including inhibiting cell proliferation, invasion and migration, while promoting cell apoptosis. Our data provided evidence that DNA methylation in SPARC gene may play a role in the progression of T-NHL.

AEG-1 is involved in hypoxia-induced autophagy and decreases chemosensitivity in T-cell lymphoma.

BACKGROUND: This study was to examine the link between astrocyte elevated gene-1 (AEG-1) and hypoxia induced-chemoresistance in T-cell non-Hodgkin's lymphoma (T-NHL), as well as the underlying molecular mechanisms. METHODS: Expression of AEG-1, LC3-II, and Beclin-1 were initially examined in human T-NHL tissues (n = 30) and normal lymph node tissues (n = 16) using western blot, real-time PCR and immunohistochemistry. Western blot was also performed to analyze the expression of AEG-1, LC3-II, and Beclin-1 in T-NHL cells (Hut-78 and Jurkat cells) under normoxia and hypoxia. Additionally, the proliferation and apoptosis of Hut-78 cells exposed to different concentration of Adriamycin (ADM) in normoxia and hypoxia were evaluated by MTT and Annexin-V FITC/PI staining assay. Finally, the effects of AEG-1 on Hut-78 cells exposed to ADM in hypoxia were assessed by MTT and Annexin-V FITC/PI staining assay, and 3-MA (autophagy inhibitor) was further used to determine the underlying mechanism. RESULTS: AEG-1, LC3-II and Beclin-1 expression were significantly increased in T-NHL tissues compared with normal tissues. Incubation of Hut-78 and Jurkat cells in hypoxia obviously increased AEG-1, LC3-II and Beclin-1 expression. Hypoxia induced proliferation and reduced apoptosis of Hut-78 cells exposed to ADM. AEG-1 overexpression further increased proliferation and decreased apoptosis of Hut-78 cells exposed to ADM in hypoxia. Moreover, overexpression of AEG-1 significantly inversed 3-MA induced-changes in cell proliferation and apoptosis of Hut-78 cells exposed to ADM in hypoxia. CONCLUSIONS: This study suggested that AEG-1 is associated with hypoxia-induced T-NHL chemoresistance via regulating autophagy, uncovering a novel target against hypoxia-induced T-NHL chemoresistance.

TIPE2 suppresses progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/ß-catenin pathway.

BACKGROUND: Esophageal carcinoma is the eighth prevalent malignancy and ranks the sixth in carcinoma-related death worldwide. Tumor necrosis factor-α-induced protein-8 like-2 (TIPE2) has been identified as a tumor suppressor in multiple carcinomas. However, its roles and molecular mechanisms underlying esophageal carcinoma progression are still undefined till now. METHODS: RT-qPCR assay was employed to detect the expression of TIPE2 mRNA. TIPE2 protein expression was measured by using western blot assay. Ad-V and Ad-TIPE2 adenoviruses were constructed to overexpress TIPE2. The effects of TIPE2 overexpression on cell proliferation, invasion and apoptosis were assessed by MTT and Edu incorporation assays, transwell invasion assay and flow cytometry analysis, respectively. The effect of TIPE2 overexpression on xenograft tumor growth was determined by measuring tumor volume and weight, together with immunohistochemistry assay. The effect of TIPE2 overexpression on the Wnt/ß-catenin signaling pathway was evaluated by detecting the protein levels of ß-catenin, c-Myc and cyclinD1 in EC9076 cells and xenograft tumors of esophageal carcinoma. RESULTS: TIPE2 expression was downregulated in esophageal carcinoma tissues and cells. Adenovirus-mediated TIPE2 overexpression suppressed cell proliferation and invasion, and induced apoptosis in esophageal carcinoma cells. Enforced expression of TIPE2 inhibited tumor growth in vivo, as evidenced by the reduced tumor volume, tumor weight and proliferating cell nuclear antigen expression. Overexpression of TIPE2 inhibited the Wnt/ß-catenin signaling pathway in esophageal carcinoma in vitro and in vivo. CONCLUSIONS: These results suggest that TIPE2 suppressed progression and tumorigenesis of esophageal carcinoma via inhibition of the Wnt/ß-catenin pathway.

Conserved cell populations in doxorubicin-resistant human nasal natural killer/T cell lymphoma cell line: super multidrug resistant cells?

BACKGROUND: Extranodal NK/T-cell lymphoma, nasal type (ENKL) is a distinct clinicopathological entity and EBV-associated disease that is highly aggressive. Many patients had failed to respond to conventional chemotherapy or relapsed after treatment. Multi-drug resistance is a major cause that leads to these desperate failures. However, the specific mechanism of drug resistance is still unclear. METHODS: In the previous study, we firstly developed a doxorubicin-resistant ENKL cell line known as SNK-6/ADM, and then a small quantity of side population (SP) cells were derived from SNK-6/ADM and named SNK-6/ADM-SP. In order to explore the biological characteristics and mechanism of drug-resistance of these cells, SNK-6, SNK-6/ADM and SNK-6/ADM-SP cells were utilized to evaluate potentially differences of chemotherapy resistance index (RI), morphology, proliferation, cell cycles, expression of ATP-binding cassette (ABC) transporters (ABCG1, ABCG2 and ABCC4) and surface markers, cytokine sensitivity, and situation of EBV infection. RESULTS: We identified SNK-6/ADM-SP is a specific multidrug resistant cell population with a higher level of RI than SNK-6/ADM. Relevant evaluations showed that SNK-6/ADM-SP presented a series of conserved biological behaviors including relatively poor proliferation ability, high expression of ABCG2, weak sensitivity to IL-15 which could stimulate normal ENKL cells' proliferation and differentiation, and EBV inhibition with low level of EBV-DNA replication and EBV-antigen expression. CONCLUSIONS: This discovered cellular heterogeneity of ENKL could provide a new perspective to better understand the mechanisms of drug resistance and overcome elusive response to chemotherapy of ENKL.

MiR-199a mediated the dissemination of human mantle cell lymphoma by interacting with the CCR7/CCL21 pair.

Mantle cell lymphoma (MCL) is a rare but deadly subtype of non-Hodgkin's lymphomas because of it can progress rapidly and has a poor prognosis. MicroRNA-199a (miR-199a) is a potential diagnostic marker and therapeutic target for MCL patients. However, the function and molecular mechanisms of miRNA-199a in MCL cells are still unclear. In this study, we first analyzed the levels of miR-199a and C-C chemokine receptor 7 (CCR7) in the tumor tissues and tumor-adjacent tissues, and found that the level of miRNA-199a was lower, whereas the level of CCR7 was higher in tumor tissues. Moreover, overexpression of miR-199a in MCL cells downregulated the level of CCR7. Then, it was found that chemokine (C-C motif) ligand 21 (CCL21), a ligand of CCR7, promoted Granta-519 and Mino cell growth and migration in a concentration-dependent and time-dependent manner. Otherwise, the CCL21/CCR7 pair elevated the level of phosphorylation of protein kinase B and extracellular regulated protein kinases 1/2, upregulated the level of matrix metalloproteinases-2, matrix metalloproteinases-9, and the markers of the mesenchymal phenotype (N-cadherin and vimentin), as well as decreased the level of E-cadherin. However, the functions of CCL21/CCR7 in the growth, migration, and dissemination of MCL cells were decreased by overexpression of miR-199a. Thus, miR-199a inhibited the dissemination of MCL cells by reversing the function of CCL21/CCR7, providing a theoretical basis for miRNA-199a as a potential novel diagnostic marker and therapeutic target for MCL patients.

Fotemustine, teniposide and dexamethasone versus high-dose methotrexate plus cytarabine in newly diagnosed primary CNS lymphoma: a randomised phase 2 trial.

OBJECTIVE: This prospective, randomized, controlled and open-label clinical trial sought to evaluate the tolerability and efficacy of the FTD regimen (fotemustine, teniposide and dexamethasone) compared to HD-MA therapy (high-dose methotrexate plus cytarabine) and to elucidate some biomarkers that influence outcomes in patients with newly diagnosed primary CNS lymphoma. METHODS: Participants were stratified by IELSG risk score (low versus intermediate versus high) and randomly assigned (1:1) to receive four cycles of FTD or HD-MA regimen. Both regimens were administered every 3 weeks and were followed by whole-brain radiotherapy. The primary endpoints were overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). RESULTS: Between June 2012, and June 2015, 52 patients were enrolled, of whom 49 patients were randomly assigned and analyzed. Of the 49 eligible patients, no significant difference was observed in terms of ORR between FTD (n = 24) and HD-MA (n = 25) groups (88% versus 84%, respectively, P = 0.628). Neither the 2-year PFS nor the 3-year OS rate differed significantly between FTD and HD-MA groups (37% versus 39% for 2-year PFS, P = 0.984; 51% versus 46% for 3-year OS, P = 0.509; respectively). The HD-MA group showed more serious neutropenia (P = 0.009) than the FTD group. High Bcl-6 expression correlated with longer OS (P = 0.038). CONCLUSIONS: FTD chemotherapy appeared to be safe and effective for PCNSL patients. High Bcl-6 expression correlated with longer survival.

A randomized controlled study of bedside electrocardiograph-guided tip location technique & the traditional chest radiography tip location technique for peripherally inserted central venous catheter in cancer patients.

Background & objectives: The peripherally inserted central catheter (PICC) has the advantages of higher safety, lower infection rate and longer retention time than peripherally inserted catheter. This study was aimed to evaluate the accuracy and safety of bedside electrocardiograph (ECG)-guided tip location technique in PICC in cancer patients, and compared with traditional chest radiography tip location technique. Methods: Patients were randomly assigned into two groups: The ECG test group patients underwent PICC insertion with ECG-guided tip location, while the control group patients had PICC insertion by the conventional method. The precision of tip location was verified by chest radiography in both groups. The groups were compared with regard to the accuracy of tip placement, anxiety levels before and after the procedure; medical cost and incidence of complications at one week, three months and six months after PICC insertion. Results: Accurate tip location was achieved in 99.30 per cent in the ECG test group vs 92.30 per cent in the control group (P<0.001). At 24 h after the procedure, the anxiety level was significantly lower in the ECG test group. The presence of thrombogenesis was significantly lower in the ECG test group at both three months and six months after the procedure (P=0.04 and P=0.03, respectively). Interpretation & conclusions: The ECG-guided PICC tip location technique was accurate and caused fewer procedure-related complications and less anxiety in patients compared to chest radiography tip location technique. Radiographic confirmation of PICC tip position may not be needed when ECG guidance is used and thus it can help avoid radiation exposure.

The efficacy and safety of gemcitabine, cisplatin, prednisone, thalidomide versus CHOP in patients with newly diagnosed peripheral T-cell lymphoma with analysis of biomarkers.

We compared the efficacy and safety of gemcitabine, cisplatin, prednisone and thalidomide (GDPT) with standard CHOP regimen (cyclophosphamide, doxorubicin, vincristine, prednisone) for patients with newly diagnosed peripheral T-cell lymphoma (PTCL) in a prospective randomized controlled and open-label clinical trial. Between July 2010 and June 2016, 103 patients were randomly allocated into two groups, of whom 52 were treated with GDPT therapy and 51 with CHOP therapy. The 2-year progression-free survival (PFS) and overall survival (OS) rates were better in the GDPT group than in the CHOP group (57% vs. 35% for 2-year PFS, P = 0·0035; 71% vs 50% for 2-year OS, P = 0·0001). The complete remission rate (CRR) and the overall response rate (ORR) in the GDPT group were higher than in the CHOP group (52% vs. 33%, P = 0·044 for CRR; 67% vs. 49%, P = 0·046 for ORR). Haemocytopenia was the predominant adverse effect, and acute toxicity was moderate, tolerable and well managed in both arms. mRNA expression of ERCC1, RRM1, TUBB3 and TOP2A genes varied among patients but the difference did not reach statistical significance, mainly due to the relatively small sample size. The precise characters of these biomarkers remain to be identified. In conclusion, GDPT is a promising new regimen as potential first-line therapy against PTCL. This study was registered at www.clinicaltrials.gov as #NCT01664975.

Drug-induced skin toxicity and clinical nursing of VitK cream on colorectal cancer patients.

To discuss the impact of 0.1% vitamin K1 (VitK1) cream on cetuximab-induced skin toxicity for colorectal cancer patients. 60 colorectal cancer patients with cetuximab therapy after hospitalization, were divided into experimental group (Ward A) and control group (Ward B) according to personnel sequential number, with 30 cases in each group. Routine nursing was implemented on control group. For experimental group, on the routine nursing basis, 0.1% VitK1 cream was smeared on face, neck, chest, back and nail (toenail) edge with three times one day at the application of cetuximab day. After cetuximab applied in 8 weeks, both skin itch and dry skin for patients in experimental group were significantly improved compared those in control group, showing statistically significant difference (W=708.000, P=0.001: W=662. 500, P=0.000). 0.1% VitK1 cream was conducive to improve both skin itch and dry skin symptoms in the cetuximab-induced skin toxicity for colorectal cancer patients.

A chemically sulfated polysaccharide derived from Ganoderma lucidum induces mitochondrial-mediated apoptosis in human osteosarcoma MG63 cells.

To develop new anticancer agents, we prepared a sulfated polysaccharide (SCGLP1) from the fruiting bodies of Ganoderma lucidum, and the effect of SCGLP1 on human osteosarcoma MG63 cell line was investigated. Our result showed that treatment with SCGLP1 resulted in a significant inhibitory effect on cell proliferation and cell viability of MG63 cells in a dose- and time-dependent manner and caused apoptotic death in MG63 cells through an increase in G0/G1 phase arrest, but had minor cytotoxic effect on human normal osteoblast (NHOst) cells. Western blot analysis identified that SCGLP1-induced apoptosis was associated with an increased protein expression of proapoptotic Bax and Bad, decreased expression of antiapoptotic Bcl-2 and Bcl-XL, loss of mitochondrial membrane potential (Δψm), the release of mitochondrial cytochrome c to cytosol, and cleavage of caspase-9, caspase-3, and poly(ADP-ribose) polymerase (PARP). In addition, pretreatment with the pan-caspase inhibitor (z-VAD-fmk) blocked the SCGLP1-induced apoptosis in MG63 cells. The data indicate that SCGLP1-induced apoptosis is primarily associated with caspase-3- and caspase-9-dependent apoptotic pathway.

Clinical analysis of chronic lung injury in patients with non-Hodgkin lymphoma after CHOP chemotherapy.

We conducted a preliminarily study on the clinical characteristics of chronic lung injury (CLI) in patients with non-Hodgkin lymphoma (NHL) after CHOP chemotherapy and observed the effects of this injury on CHOP treatment efficacy. Sixty patients who were diagnosed as NHL and received CHOP chemotherapy in hospital were enrolled for this clinical trial. CLI was assessed by clinical symptoms and computed tomography (CT) scan conducted before and after chemotherapy. The effect of CLI on the efficacy of CHOP chemotherapy in patients with NHL was evaluated by comparing treatment response and recurrence rate to patients with no signs of lung injury. Our CT scans revealed multiple signs of CLI in 35 patients (56.67 %), such as pulmonary diffuse, limited infiltration shadow or ground glass-like changes. Among them, 23 patients (38.33 %) showed bilateral diffuse lung injury and 12 (20.00 %) showed topical lung injury. Most patients suffering from 6 to 12 months delayed recurrence exhibited signs of CLI. The inflammatory response of CLI may increase the risk of disease progression and recurrence. Therefore, early diagnosis and intervention, which play a positive role in the clinical treatment and the long-term efficacy, are critical for patients with NHL.

Effectiveness of gemcitabine, pegaspargase, cisplatin, and dexamethasone (DDGP) combination chemotherapy in the treatment of relapsed/refractory extranodal NK/T cell lymphoma: a retrospective study of 17 patients.

The prognosis of extranodal nature killer (NK)/T cell lymphoma (ENKL) is dismal because of its aggressive course and multidrug resistance. Currently, for patients with relapsed/refractory ENKL, L-asparaginase-based regimens such as L-asparaginase, ifosfamide, methotrexate, etoposide, and dexamethasone (SMILE) or L-asparaginase, methotrexate, and dexamethasone (AspaMetDex) are recommended. We retrospectively investigated the efficacy and safety of gemcitabine, pegaspargase, cisplatin, and dexamethasone (DDGP) combination chemotherapy in the treatment of 17 relapsed/refractory ENKL patients. Clinical data from these patients were collected and analyzed. The primary end point was overall response rate (ORR). All patients were subjected to 2 to 6 cycles of DDGP chemotherapy, and the median number of cycles of DDGP regimen administrated was four. The ORR was 88.2 % (15/17), with nine patients (52.9 %) achieved complete response (CR) and six patients (35.3 %) achieved partial response (PR). The median follow-up time was 17 months (range 2-28 months). The 1-year overall survival (OS) rate and 1-year progression-free survival (PFS) were 82.4 and 64.7 %, respectively. For those CR responders, the median PFS was 17 months. Grade 3/4 neutropenia occurred in nine patients (52.9 %) and grade 3/4 thrombocytopenia occurred in six patients (35.3 %). DDGP combination chemotherapy produces favorable outcomes in relapsed/refractory ENKL, and more attention should be paid to treatment-related myelosuppression. Further prospective trials are expected to define the efficacy.