A Stepwise Interventional Strategy for the Removal of Adherent Totally Implanted Central Venous Access Port Catheters.

BACKGROUND: To evaluate the safety and effectiveness of a stepwise interventional strategy for the removal of adherent totally implanted central venous access port catheters, consisting of a guidewire support, antegrade coaxial separation, and retrograde coaxial separation with increasing technical complexity. METHODS: This study has a retrospective design. Thirty-two patients who had failed routine removal of the port catheter and were then transferred to interventional radiology between November 2017 and December 2023 were reviewed. The technical success and complication rates were recorded. RESULTS: All adherent catheters were successfully removed without catheter fragmentation, using guidewire support (n = 21), antegrade coaxial separation (n = 5), and retrograde coaxial separation (n = 6). The technical success rate was 100%, and no complications occurred. CONCLUSIONS: The proposed stepwise interventional strategy successfully removed adherent port catheters, with good safety and high effectiveness. It appeared to reduce the incidence of catheter fracture during the removal of adherent totally implantable central venous access port catheters.

[Analysis of Histologic Transformation and Prognosis for Follicular Lymphoma].

OBJECTIVE: To investigate the related factors of invasive transformation and prognosis for follicular lymphoma. METHODS: A total of 168 patients with follicular lymphoma at First Affiliated Hospital of Zhengzhou University from August 2015 to January 2021 were collected, and the significance of each index in histological transformation (HT) and prognosis were analyzed. RESULTS: Pathology grade3, Ki-67 index ≥40%, ß2MG＞3 mg/L, LDH＞245 U/L, POD24 and non-invasion of bone marrow were associated with HT. Univariate analysis showed that the high risk of FLIPI-2, pathological grade 3, Ki-67≥40%, anemia, ß2MG＞3 mg/L, LDH＞245 U/L and HT had significant adverse effects on PFS; ß2MG＞3 mg/L, LDH＞245 U/L, POD24 and HT had significant adverse effects on OS. Cox multivariate analysis showed that the ß2MG >3 mg/L and HT were independent risk factors of PFS, HT was independent risk factor of OS. CONCLUSION: The pathological grade, Ki-67, ß2MG, LDH, POD24 and bone marrow invasion of FL can predict the risk of HT. Meanwhile, ß2MG >3 mg/L and HT are significantly related to poor prognosis of FL.

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.

A multicenter retrospective study on the real-world outcomes of autologous vs. allogeneic hematopoietic stem cell transplantation for peripheral T-cell lymphoma in China.

BACKGROUND: There were few studies on real-world data about autologous hematopoietic stem cell transplantation (auto-HSCT) or allogeneic HSCT (allo-HSCT) in peripheral T-cell lymphoma (PTCL). This study aimed to investigate the clinical outcomes of patients who received auto-HSCT or allo-HSCT in China. METHODS: From July 2007 to June 2017, a total of 128 patients who received auto-HSCT (n  = 72) or allo-HSCT (n  = 56) at eight medical centers across China were included in this study. We retrospectively collected their demographic and clinical data and compared the clinical outcomes between groups. RESULTS: Patients receiving allo-HSCT were more likely to be diagnosed with stage III or IV disease (95% vs. 82%, P = 0.027), bone marrow involvement (42% vs. 15%, P = 0.001), chemotherapy-resistant disease (41% vs. 8%, P = 0.001), and progression disease (32% vs. 4%, P < 0.001) at transplantation than those receiving auto-HSCT. With a median follow-up of 30 (2-143) months, 3-year overall survival (OS) and progression-free survival (PFS) in the auto-HSCT group were 70%(48/63) and 59%(42/63), respectively. Three-year OS and PFS for allo-HSCT recipients were 46%(27/54) and 44%(29/54), respectively. There was no difference in relapse rate (34%[17/63] in auto-HSCT vs. 29%[15/54] in allo-HSCT, P = 0.840). Three-year non-relapse mortality rate in auto-HSCT recipients was 6%(4/63) compared with 27%(14/54) for allo-HSCT recipients (P = 0.004). Subanalyses showed that patients with lower prognostic index scores for PTCL (PIT) who received auto-HSCT in an upfront setting had a better outcome than patients with higher PIT scores (3-year OS: 85% vs. 40%, P = 0.003). Patients with complete remission (CR) undergoing auto-HSCT had better survival (3-year OS: 88% vs. 48% in allo-HSCT, P = 0.008). For patients beyond CR, the outcome of patients who received allo-HSCT was similar to that in the atuo-HSCT group (3-year OS: 51% vs. 46%, P = 0.300). CONCLUSIONS: Our study provided real-world data about auto-HSCT and allo-HSCT in China. Auto-HSCT seemed to be associated with better survival for patients in good condition (lower PIT score and/or better disease control). For patients possessing unfavorable characteristics, the survival of patients receiving allo-HSCT group was similar to that in the auto-HSCT group.

Clinical features and treatment outcomes of primary ocular adnexal mucosa-associated lymphoid tissue lymphoma: a single center retrospective analysis of 64 patients in China.

AIM: To investigate the clinical features, treatment and prognosis of primary ocular adnexal mucosa-associated lymphoid tissue lymphoma (POAML). METHODS: A retrospective analysis was performed on 64 patients with POAML who were admitted to the First Affiliated Hospital of Zhengzhou University from January 2006 to December 2018. RESULTS: With a median follow-up of 61mo (range, 2-156mo), estimated overall survival (OS) rate and progression-free survival (PFS) rate at 10y reached 94.5% and 61.5%, respectively. Median OS time and PFS time were not reached. During this period, only 3 patients died, but none of them died directly due to disease progression. One patient (1.6%) developed transformation to diffuse large B-cell lymphoma (DLBCL). Of the 56 patients achieved complete remission after first-line treatment, 5 (8.9%) developed local and/or systemic relapse eventually. Patients ≥60y had significantly shorter PFS than younger patients (P=0.01). For patients with early stages (Ann Arbor stage I and stage II), univariate analysis confirmed that radiotherapy dose lower than 32 Gy were independently associated with shorter PFS (P=0.04). Other factors including gender, bone marrow involvement, the initial location of the disease, and the laterality were not associated with PFS. CONCLUSION: The data from our center indicate that POAML has a slow clinical progression and has an excellent clinical outcome. Patients with POAML harbor a continual risk of relaps and transformation to aggressive subtype of lymphoma.

Activated hippo signal pathway inhibits cell proliferation and promotes apoptosis in NK/T cell lymphoma cells.

BACKGROUND: Natural Killer T-Cell Lymphoma (NKTCL) is a subtype of Non-Hodgkin's Lymphoma, and its morbidity is ranked the first of T-Cell Lymphoma. Hippo signaling pathway is involved in the pathogenesis of tumors. However, the role of Hippo signaling pathway in the oncogenesis of NKTCL still remains unclear. METHODS: The expressions of mammalian sterile 20-like kinase 1 (MST1) and Yes-associated protein (YAP) were investigated by RT-PCR and Western blotting. Cell viability was detected by MTT assays. Cell cycle and cell apoptosis were determined by flow cytometry. Cell proliferative capacity was detected by colony formation assay. Nude mice xenograft models were established and the tumor sections were analyzed by immunohistochemistry (IHC) staining. RESULTS: The expression of MST1 was significantly down-regulated in NKTCL tissues (n = 30) and cell lines, while the expression of YAP was significantly up-regulated, and the phosphorylation of YAP was inhibited. Overexpression of MST1, knockdown of YAP, or verteporfin (VP) treatment could inhibit cell proliferation, and promote cell cycle arrest and apoptosis in NKTCL cells, while knockdown of MST1 and overexpression of YAP promoted cell proliferation. Additionally, Bcl-2/Bax ratio and downstream effectors of Hippo signaling pathway (c-myc, survivin, cyclinD1, CTGF, and TEAD) were significantly decreased when MST1 was overexpressed and YAP was knocked down or after VP treatment. Furthermore, our mice model demonstrated that activation of Hippo signal pathway suppressed the tumorigenesis of NKTCL. CONCLUSION: The activation of Hippo signal pathway via overexpressing MST1 or down-regulating YAP can inhibit the tumorigenesis of NKTCL.

Prognostic significance of CD30 expression in nasal natural killer/T-cell lymphoma.

The present study aimed to investigate the expression of tumor necrosis factor receptor superfamily member 8 (CD30) in extranodal natural killer/T-cell lymphoma (ENKTL) using immunohistochemistry, and to evaluate the association between CD30 and clinicopathological and prognostic significance. CD30 expression was detected using immunohistochemistry on paraffin-embedded sections obtained from 122 patients with ENKTL prior to treatment. In total, 70 of these patients with complete clinical data were collected for prognostic analysis. The level of CD30 expression, of the 122 patients with ENKTL, was grouped on the basis of a 5-tiered scale as follows: 0%, no staining; 1+, <25% positive cells; 2+, 25-50% positive cells; 3+, 50-75% positive cells; and 4+, >75% positive cells). In total, 36 (29.5%) were classified as 0; 46 (37.7%) as 1+; 22 (18.0%) as 2+; 12 (9.8%) as 3+; and 6 (4.9%) as 4+. Among the 86 patients with scores between 1+ and 4+, the membranous staining patterns of CD30 expression were sporadic (33.7%), focal (43.2%), diffuse (15.1%) and angiocentric (8.1%). When considering a score of ≥3+ as CD30 positivity (CD30+), the CD30+ group had significantly shorter overall survival rates (P=0.0023) and progression-free survival rate (P=0.0008) compared with CD30 negative group. However, no statistically significant association was found between CD30 expression and clinicopathological features (P<0.05). The present study found that the expression of CD30 (≥3+) was significantly associated with poor prognosis but was not associated with clinical and histopathological parameters in ENKTL. Therefore, CD30 may be a useful prognostic marker in ENKTL.

Fotemustine, teniposide and dexamethasone in treating patients with CNS lymphoma.

PURPOSE: We developed and evaluated a regimen including fotemustine, teniposide and dexamethasone (FTD) for treating patients with central nervous system (CNS) lymphoma based on pharmacokinetic properties of individual agents and in combination. PATIENTS AND METHODS: In a comparison study, 8 patients with primary CNS lymphoma (PCNSL) and 8 with secondary CNS lymphoma (SCNSL) were treated with FTD (comprising fotemustine 100 mg/m2, 1h infusion, day 1; teniposide 60 mg/m2, >0.5 h infusion, on day 2, 3, 4; dexamethasone 40 mg, 1h infusion, on day 1, 2, 3, 4 and 5; and methotrexate 12 mg, cytosine arabinoside 50 mg plus dexamethasone 5 mg intrathecally, on day 2 and 7). Cycles were repeated every 3 weeks. After response assessment, patients received whole brain radiotherapy. RESULTS: Of the 8 PCNSL patients, 4 (50%) achieved CR and 3 (38%) PR, an overall response rate of 88%. Four patients (50%) were in continuing remission at the end of this study after a median follow-up of 30 months (range 10 to 56 months). Of the 8 SCNSL patients the overall response rate was 63% (CR+PR:38%+25%). All responses were achievable with predictable toxicity mainly reflecting reversible myelosuppression. CONCLUSION: This study suggests that FTD could be an effective treatment for CNS lymphoma, and is worthy of further evaluation.

[Experimental study of extract from Prunella vulgaris inducing B, T lymphoma cell apoptosis].

OBJECTIVE: To investigate the effects of extract from Prunella vulgaris on proliferation of human B lymphoma cell line Raji cells anf T lymphoma cell line Jurkat cells and discuss the mechanism. METHODS: Used different concentrations of extract from Prunella vulgaris to treat Raji and Jurkat cells and collected cells after 48 h respectively, the proliferation inhibition rate, the DNA Ladder and the apoptosis rate of Raji and Jurkat cells were examined by MTT assay, agarose gel electrophoresis and flow cytometry respectively; Western blot was used to detect the change of BCL-2, BAX protein. RESULTS: Different concentrations of the extract from Prunella vulgaris could inhibit the proliferation of both Raji and Jurkat cells remarkably (P < 0.01), the IC50 of Raji cells, 18.01 +/- 0.92 microg/mL, was lower than that of Jurkat, the difference was significant statistically (P < 0.05); Apoptosis related DNA Ladder appeared after treated Raji and Jurkat cells with the extract from Prunella vulgaris; Compared with the control group, with the increase of the concentration of the extract from Prunella vulgaris, the early cell apoptosis rate of Raji and Jurkat were all increased,the early cell apoptosis rate of the extract from Prunella vulgaris of 15, 20 and 25 microg/mL treated Raji and Jurkat cells were (9.46 +/- 0.25)%, (21.68 +/- 0.46)%, (35.03 +/- 0.35)% and (4.06 +/- 0.14)%, (13.59 +/- 0.23)%, (22.92 +/- 0.20)% respectively. With the same concentration, the early apoptosis rate of Raji cells was higher than that of Jurkat cells significantly (P < 0.01); Compared with the control group, with the in- crease of the concentration of the extract from Prunella vulgaris, the expression of BCL-2 protein was down-regulated and BAX up-regulated, With the same concentration, the decline degree of BCL-2 protein expression and the increase degree of BAX protein expression in Raji cells was more remarkable than that in Jurkat cells, the difference was significant (P < 0.05). CONCLUSION: The extract from Prunella vulgaris can inhibit the proliferation of lymphoma cells and the inhibition is realized by inducing apoptosis, the mechanism of inducing cell apoptosis with extract from Prunella vulgaris is probably related with the BAX and BCL-2 protein expression, the inhibition effect on Raji cells is greater than that of Jurkat cells.

[Construction of a lentiviral vector carrying TRAIL gene and its infection efficiency to lymphoma cells in vitro].

This study was purposed to construct a lentiviral vector carrying the TNF-related apoptosis-inducing ligand (TRAIL) gene and investigate its infection efficiency to several lymphoma cells lines. A pGM-T-TRAIL vector was constructed by inserting the cDNA segment derived from TRAIL mRNA into the cloning vector pGM-T, which was then inserted into the lentiviral vector pWPI. The recombinant lentiviral vector plenti-TRAIL was produced by transfecting 293T cells with pWPI-TRAIL, packaging plasmid Δ8.2, and envelope plasmid pCMV-VSVG and then harvested from the culture supernatant. Infection efficiency was measured in several lymphoma cell lines by live cell GFP fluorescence, while TRAIL expression was assessed by RT-PCR and Western blot. The results showed that the enzyme cut identification and sequencing demonstrated the successful construction of both pGM-T-TRAIL and pWPI-TRAIL. The results of testing drop showed that the concentration of the restructured lentiviral plenti-TRAIL reached 10(9) IU/ml. Comparison of infection efficiency revealed that YTS cells were more likely to be infected than DOHH2 or Jurkat cells (P < 0.05). Finally, RT-PCR and Western blot showed that lymphoma cells infected with plenti-TRAIL were able to efficiently express the TRAIL mRNA and protein. It is concluded that the lentiviral vector pWPI-TRAIL is successfully constructed and the recombinant lentiviral plenti-TRAIL is manufactured. The plenti-TRAIL vector is able to infect several lymphoma cell lines, and the infected lymphoma cells can effectively express TRAIL genes.

[Expression and significance of matrix metalloproteinase and tissue inhibitor of matrix metalloproteinase in non-melanoma skin cancer].

OBJECTIVE: To investigate the expression and significance of matrix metalloproteinases (MMP-2, MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-2, TIMP-1) in non-melanoma skin cancer (NMSC). METHODS: Thirty six patients with squamous cell carcinoma (SCC) and 32 patients with basal cell carcinoma (BCC), confirmed by pathology, were selected, and 30 cases of normal skin were selected as control. The expression of MMP-2, MMP-9, TIMP-1 and TIMP-2 in all samples were examined by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). The expression rate, expression intensity and expression level of each factor were recorded. The results were compared between the groups. RESULTS: The expression rates of MMP-2 and MMP-9 in the control group were 30.0% and 36.7%, the expression levels of MMP-2 and MMP-9 in the control group were 57.216 ± 12.785 and 59.318 ± 13.262, all significantly lower than those in the tumor edge and center of the SCC and BCC groups (P < 0.01). The expression rates of TIMP-1 and TIMP-2 in the control group were 96.7% and 100%, their expression levels were 121.738 ± 25.516 and 122.612 ± 25.964, all significantly higher than those in the SCC and BCC groups (P < 0.01). The expression levels of MMP-2 and MMP-9 in the tumor center and edge of SCC group were significantly higher than those in the corresponding parts of the BCC group, while the expression levels of TIMP-1 and TIMP-2 were significantly lower than those in the BCC group (P < 0.01). The expression levels of MMP-2 and MMP-9 in the tumor edge of the SCC and BCC groups were significantly higher than those in the tumor centers (P < 0.01), while the expression levels of TIMP-1and TIMP-2 were significantly lower than those in the tumor centers (P < 0.01). CONCLUSION: MMP-2, MMP-9 and TIMP-2, TIMP-1 may play an important role in the development, progression, invasion and metastasis of non-melanoma skin cancer.

[Study on proteomics of Jurkat cells treated with the extracts from Prunella vulgaris].

OBJECTIVE: To analyse the differential proteins of Jurkat cells after treated with the extracts from Prunella vulgaris using two-dimensional electrophoresis and mass spectrum. METHODS: Jurkat cell growth inhibitive effect of the extracts from Prunella vulgaris was analyzed by MTT assay. The total proteins of the cells were extracted after treated with the extracts in a dose of 20 microg/mL. Then 2D and MALDI-TOF-MS were used to assess the differential proteins. RESULTS: The extracts from Prunella vulgaris could depress the proliferation of Jurkat cells in a dose-dependent manner. After 2-DE and MALDI-TOF-MS,11 proteins were identified successfully, including glyceraldehyde-3-phosphate dehydrogenase, coagulation factor VII, Heterogeneous nuclear ribonucleoprotein L, heat shock 70 kDa protein 8 isoform 2, immunoglobulin heavy chain variable region, heterogeneous nuclear ribonucleoprotein A2/B1, zinc finger protein 43, chaperonin containing TCP1, subunit 6A (zeta 1), isoform CRA_b, etc. CONCLUSION: The extracts from Prunella vulgaris could inhibit the growth of Jurkat cells significantly, and lead the proteomics change of Jurkat cells, which may be related to the anti-tumor effect of the extracts from Prunella vulgaris.

Analysis of serum proteome profiles of non-Hodgkin lymphoma for biomarker identification.

Serum samples from non-Hodgkin lymphoma (NHL) patients who had not undergone chemotherapy, lymphnoditis patients, and healthy adults were analyzed using surface-enhanced laser desorption-ionization time-of-flight mass spectrometry (SELDI-TOF MS) to detect the differentially expressed serum proteins. Models were developed to distinguish between the healthy adult group and the NHL group, with a sensitivity of 69% and specificity of 90%, and between the lymphnoditis group and the NHL group with a sensitivity of 74% and specificity of 84%. A protein with the m/z of M10 197.91 u was expressed at a significantly higher level in the NHL group, compared to the other groups. Furthermore, differences were also significant among different stages of NHL and among samples with different International Prognosis Index (IPI) scores or lactase dehydrogenase (LDH) levels. The three identified proteins may offer a new serological approach for early diagnosis, differential diagnosis, and pathogenic investigation of NHL. And the protein with the m/z of M10 197.91 u may be a new serological biomarker for monitoring treatment response and evaluating the prognosis of patients with NHL.