MK8617 inhibits M1 macrophage polarization and inflammation via the HIF-1α/GYS1/UDPG/P2Y14 pathway.

Background: Nonresolving inflammation is a major driver of disease and needs to be taken seriously. Hypoxia-inducible factor (HIF) is closely associated with inflammation. Hypoxia-inducible factor-prolyl hydroxylase inhibitors (HIF-PHIs), as stabilizers of HIF, have recently been reported to have the ability to block inflammation. We used MK8617, a novel HIF-PHI, to study its effect on macrophage inflammation and to explore its possible mechanisms. Methods: Cell viability after MK8617 and lipopolysaccharide (LPS) addition was assessed by Cell Counting Kit-8 (CCK8) to find the appropriate drug concentration. MK8617 pretreated or unpretreated cells were then stimulated with LPS to induce macrophage polarization and inflammation. Inflammatory indicators in cells were assessed by real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR), western blot (WB) and immunofluorescence (IF). The level of uridine diphosphate glucose (UDPG) in the cell supernatant was measured by ELISA. Purinergic G protein-coupled receptor P2Y14, as well as hypoxia-inducible factor-1α (HIF-1α) and glycogen synthase 1 (GYS1) were detected by qRT-PCR and WB. After UDPG inhibition with glycogen phosphorylase inhibitor (GPI) or knockdown of HIF-1α and GYS1 with lentivirus, P2Y14 and inflammatory indexes of macrophages were detected by qRT-PCR and WB. Results: MK8617 reduced LPS-induced release of pro-inflammatory factors as well as UDPG secretion and P2Y14 expression. UDPG upregulated P2Y14 and inflammatory indicators, while inhibition of UDPG suppressed LPS-induced inflammation. In addition, HIF-1α directly regulated GYS1, which encoded glycogen synthase, an enzyme that mediated the synthesis of glycogen by UDPG, thereby affecting UDPG secretion. Knockdown of HIF-1α and GYS1 disrupted the anti-inflammatory effect of MK8617. Conclusions: Our study demonstrated the role of MK8617 in macrophage inflammation and revealed that its mechanism of action may be related to the HIF-1α/GYS1/UDPG/P2Y14 pathway, providing new therapeutic ideas for the study of inflammation.

Environmental Impact Assessment for the Use of an Orally Aerosolized Adenovirus Type-5 Vector-Based COVID-19 Vaccine in Randomized Clinical Trials.

BACKGROUND: An orally aerosolized adenovirus type-5 vector-based coronavirus disease 2019 (COVID-19) vaccine (Ad5-nCoV) has recently been authorized for boosting immunization in China. Our study aims to assess the environmental impact of the use of aerosolized Ad5-nCoV. METHODS: We collected air samples from rooms, swabs from the desks on which the vaccine nebulizer was set, mask samples from participants, and blood samples of nurses who administered the inoculation in the clinical trials. The viral load of adenovirus type-5 vector in the samples and the antibody levels against the wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain in serum were detected. RESULTS: Only one (4.00%) air sample collected before initiation of vaccination was positive and most air samples collected during and after vaccination were positive (97.96%, 100%, respectively). All nurses in trial A showed at least 4-fold increase of the neutralizing antibody against SARS-CoV-2 after initiation of the study. In trial B, the proportion of positive mask samples was 72.97% at 30 minutes after vaccination, 8.11% at day 1, and 0% at days 3, 5, and 7. CONCLUSIONS: Vaccination with the orally aerosolized Ad5-nCoV could result in some spillage of the vaccine vector viral particles in the environment and cause human exposure. Clinical Trials Registration. NCT04840992 and NCT05303584.

Safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised Ad5-nCoV after two-dose priming with an inactivated SARS-CoV-2 vaccine in Chinese adults: a randomised, open-label, single-centre trial.

BACKGROUND: Due to waning immunity and protection against infection with SARS-CoV-2, a third dose of a homologous or heterologous COVID-19 vaccine has been proposed by health agencies for individuals who were previously primed with two doses of an inactivated COVID-19 vaccine. METHODS: We did a randomised, open-label, controlled trial to evaluate the safety and immunogenicity of heterologous boost immunisation with an orally administered aerosolised adenovirus type-5 vector-based COVID-19 vaccine (Ad5-nCoV) in Chinese adults (≥18 years old) who had previously received two doses of an inactivated SARS-CoV-2 vaccine-Sinovac CoronaVac. Eligible participants were randomly assigned (1:1:1) to receive a heterologous booster vaccination with a low dose (1·0 × 1011 viral particles per mL; 0·1 mL; low dose group), or a high dose (1·0 × 1011 viral particles per mL; 0·2 mL; high dose group) aerosolised Ad5-nCoV, or a homologous intramuscular vaccination with CoronaVac (0·5 mL). Only laboratory staff were masked to group assignment. The primary endpoint for safety was the incidence of adverse reactions within 14 days after the booster dose. The primary endpoint for immunogenicity was the geometric mean titres (GMTs) of serum neutralising antibodies (NAbs) against live SARS-CoV-2 virus 14 days after the booster dose. This study was registered with ClinicalTrials.gov, NCT05043259. FINDINGS: Between Sept 14 and 16, 2021, 420 participants were enrolled: 140 (33%) participants per group. Adverse reactions were reported by 26 (19%) participants in the low dose group and 33 (24%) in the high dose group within 14 days after the booster vaccination, significantly less than the 54 (39%) participants in the CoronaVac group (p<0·0001). The low dose group had a serum NAb GMT of 744·4 (95% CI 520·1-1065·6) and the high dose group had a GMT of 714·1 (479·4-1063·7) 14 days after booster dose, significantly higher than the GMT in the CoronaVac group (78·5 [60·5-101·7]; p<0·0001). INTERPRETATION: We found that a heterologous booster vaccine with an orally administered aerosolised Ad5-nCoV is safe and highly immunogenic in adults who have previously received two doses of CoronaVac as the primary series vaccination. FUNDING: National Natural Science Foundation of China and Jiangsu Provincial Key Research and Development Program.

Drug resistance biomarker ABCC4 of selinexor and immune feature in multiple myeloma.

The treatment of relapse or refractory multiple myeloma (RRMM) is still a big challenge in clinic. Recently, several clinical trials indicated that the XPO1 inhibitor, selinexor could significantly improve the remission rate in MM patients. However, the heterogeneous genetic background greatly influenced the efficiency of selinexor among MM. Here, we tried to characterized the biomarkers associated with selinexor sensitivity by analyzing gene expression data in MM patients. We found the cytogenetic background of selinexor sensitive MM patients was not limited to specific cytogenetic subtypes. In addition, by weighted gene co-expression network analysis (WGCNA), we obtained 10 key genes which showed a strong correlation with the selinexor sensitivity in MM patients. Notably, ABCC4 (MRP4) was the only gene which was both differentially expressed and proved to be clinical prognostic valuable (both for event-free survival and overall survival) in MM patients. We further validated the heterogenous expression of ABCC4 in MM cell lines and its value as a novel indicator for selinexor sensitivity. Moreover, immune infiltration analysis showed that ABCC4 expression had a significantly positive correlation with NK infiltration as well as immunotherapy target TIM-3 (HAVCR2) expression. Collectively, our findings indicated that ABCC4 might be a predictive biomarker of selinexor sensitivity in MM patients, which could be enhanced if combined with immunotherapy drugs such as TIM-3 inhibitor.

PKMYT1 Promotes Gastric Cancer Cell Proliferation and Apoptosis Resistance.

BACKGROUND: Abnormal expression of protein kinase membrane associated tyrosine/threonine 1 (PKMYT1) is closely associated with multiple types of cancers. In the present study, we examined the roles of PKMYT1 in gastric cancer (GC) progression. METHODS: We examined the expression status of PKMYT1 in GC tissues and cell lines. Meanwhile, short hairpin RNA (shRNA) was used to inhibit the endogenous expression of PKMYT1 in GC cells. Then we analyzed the effect of PKMYT1 on the malignant biological behavior of GC cells by in vitro and in vivo experiments. RESULTS: The findings showed high PKMYT1 expressions in GC tissues as well as a positive correlation between PKMYT1 expression and prognosis of patients with GC. Additional findings also revealed that PKMYT1 silencing significantly enhanced apoptosis and inhibited GC cell proliferation. In vivo, the silence of PKMYT1 inhibits tumor growth. Further analysis showed that the increase in PKMYT1 expressions led to malignant biological behavior through activation of the MAPK signaling pathway. CONCLUSION: Our data suggested that PKMYT1 promotes cell proliferation and apoptosis resistance in GC cells by activating the MAPK signaling pathway, making it a potential therapeutic target for GC.

Clinical value of DPOC for detecting and removing residual common bile duct stones (video).

BACKGROUND: This study aims to evaluate the efficacy and safety of detecting and removing residual common bile duct stones (CBDS) using direct peroralcholangioscopy (DPOC) after performing endoscopic retrograde cholangiopancreatography (ERCP) for stone retrieval. METHODS: From January 5, 2017 to December 27, 2017, a total of 164 cases of choledocholithiasis were treated by ERCP for stone retrieval. According to the inclusion and exclusion criteria, the remaining 79 cases (39 males; mean age: 63.3 years old, range: 52-79 years old) were enrolled in the present study. The maximum transverse stone diameter was 6-15 mm (12.7 ± 4.2 mm), as determined by ERCP. Furthermore, there were 57 cases of multiple stones (number of stones: two in 41 cases, three in nine cases, and ≥ 4 in seven cases), 13 cases of post-mechanical lithotripsy, and nine cases of broken stones. RESULTS: The overall success rate of DPOC was 94.9% (75/79). Furthermore, 18.7%(14/75) of cases were directly inserted, 72%(54/75) of cases required guide wire assistance, and 9.3%(7/75) of cases were successfully inserted with overtube assistance. The average insertion time was 7-17 min (4.9 ± 2.9 min). Residual stones were detected in 19 cases (25.3%), and all of which were < 5 mm in diameter. Moreover, five cases of formed stones were removed by basket and balloon catheter, while the remaining cases were cleaned after irrigation and suction. There were no serious complications. CONCLUSION: DPOC is safe and effective for both the detection and removal of residual CBDS after conventional ERCP.

Anti-inflammatory activity of resveratrol prevents inflammation by inhibiting NF­κB in animal models of acute pharyngitis.

Recent studies have demonstrated that resveratrol can reduce blood sugar, improve insulin resistance, regulate abnormalities in lipid metabolism, and lower the secretion and expression of inflammatory factors. The present study investigated the anti­inflammatory effects of resveratrol in animal models of acute pharyngitis, and its possible mechanisms. Commercial ELISA kits were used to measure tumor necrosis factor­α, interleukin (IL)­6, macrophage inflammatory protein­2, cyclooxygenase­2 levels and caspase­3/9 activity. Toll­like receptor (TLR)­4, myeloid differentiation primary response protein MyD88, phosphorylated (p)­nuclear factor (NF)­κB and p­IκB were analyzed using western blotting. In a rabbit model of acute pharyngitis, it was demonstrated that resveratrol inhibited tumor necrosis factor­α and interleukin­6 serum levels, macrophage inflammatory protein­2 and cyclooxygenase­2 activity levels, reactive oxygen species production and caspase­3/9 activity. Resveratrol suppressed NACHT, LRR and PYD domains­containing protein 3 and caspase­1 protein expression, and reduced IL­1ß and IL­18 protein expression in animal models of acute pharyngitis. Additionally, resveratrol suppressed TLR4 and myeloid differentiation primary response protein 88 protein expression, and reduced p­NF­κB and increased p­IκB protein expression in animal models of acute pharyngitis. In conclusion, these findings indicated that the anti­inflammatory activity of resveratrol prevents acute pharyngitis­induced inflammation by inhibiting NF­κB in animal models. Therefore, these data suggested an important clinical application of resveratrol in preventing acute pharyngitis.

Interim PET-CT may predict PFS and OS in T-ALL/LBL adult patients.

T lymphoblastic leukemia/lymphoma (T-ALL/LBL) is highly aggressive. Although intensive chemotherapies such as ALL-type regimens are commonly used, about half adult patients eventually relapse and die of T-ALL/LBL. Overwhelming evidences have confirmed that interim PET can predict survival outcomes and guide subsequent treatments in Hodgkin lymphoma. However, whether interim PET-CT can predict survival outcomes or not in T-ALL/LBL patients remains unclear. 47 adult patients of T-ALL/LBL were retrospectively reviewed. Interim PET-CT was done after induction therapy and evaluated according to the International Harmonization Project criteria. After induction therapy, interim PET-CT was positive in 19 patients (40.4%). After a median follow up time of 34 months, the 2-year and 3-year progression free survival (PFS) rate were 39% and 30%, respectively, and the 2-year and 3-year overall survival (OS) rate were 54% and 45%, respectively. Using Kaplan-Meier survival analysis, it was found that interim PET-CT positivity correlated with significantly inferior PFS and OS (2-year PFS rate for patients with positive or negative interim PET were 21.1% or 56.0%, respectively, p = 0.002; 2-year OS rate for patients with positive or negative interim PET were 31.6% or 63.7%, respectively, p = 0.010). However, there was no significant relationship between PFS, OS and bone marrow infiltration, lactate dehydrogenase level, and stages (p > 0.05). Interim PET-CT may predict PFS and OS in adult patients of T-ALL/LBL, which needs to be validated in prospective clinical trials. The optimal criteria for interim PET-CT evaluation and risk-adapted treatment strategy determined by interim PET-CT should be investigated in future clinical practice.

High level of soluble interleukin-2 receptor in serum predicts treatment resistance and poor progression-free survival in multiple myeloma.

The IL-2/IL-2 receptor (IL-2R) system plays a central role in maintaining normal T cell immunity, and its disturbance is associated with several hematologic disorders. Studies have found in several types of lymphoma that abnormal amounts of soluble IL-2R (sIL-2R) may result in imbalance of the IL-2/IL-2R system and hence of the T cell immunoregulation. Whether the level of sIL-2R in blood could predict treatment outcomes or not needs to be investigated in multiple myeloma (MM) patients. The level of sIL-2R in serum was measured using enzyme-linked immunosorbent assay (ELISA) in 81 patients with newly diagnosed MM. Twenty-six patients (32.1%) were treated with bortezomib-based regimens and 55patients (67.9%) received old drugs-based regimens. The mean concentration of sIL-2R for myeloma patients was 8.51 ng/ml, significantly higher than that of healthy controls (0.56 ng/ml, p < 0.0001). The best cutoff value for sIL-2R in predicting high risk for disease progression is 6.049 ng/ml with an area under curve (AUC) of 0.665 (p = 0.013). Thirty-six patients (44.4%) were classified as higher sIL-2R level group (> 6.049 ng/ml), and 45 patients (55.6%) as lower group (≤ 6.049 ng/ml). The overall response rate (ORR) was 60.0% in lower sIL-2R level group, and 41.7% in higher level group (p = 0.156). The median progression-free survival (PFS) and overall survival (OS) was 12 months (range, 2.0-65 months) and 20 months (range, 2.0-118 months), respectively. In a multivariate survival analysis, including Eastern Cooperative Oncology Group performance status score, treatment response, and sIL-2R level, it was found that all these three parameters were significantly independent prognostic factors for PFS (p = 0.032, 0.016, and 0.043, respectively), but none factors maintained their value in predicting OS. Subgroup analysis revealed that high level of sIL-2R is correlated with significantly inferior PFS in patients treated with bortezomib-based regimens (p = 0.004). Serum sIL-2R level is an independent prognostic factor for PFS, indicating novel drugs targeting the imbalance of IL-2/IL-2R system may be a promising strategy in MM.

Elevated neutrophil-to-lymphocyte ratio predicts poor outcome in patients with advanced non-small-cell lung cancer receiving first-line gefitinib or erlotinib treatment.

AIM: Elevated neutrophil-to-lymphocyte ratio (NLR) has been demonstrated to be a poor prognostic factor in multiple types of malignancies, whereas the effect of NLR on the prognosis of epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) patients treated with first-line EGFR tyrosine kinase inhibitors (TKIs) is not fully addressed. METHODS: 81 metastatic NSCLC patients harboring EGFR mutation treated with first-line EGFR TKIs were retrospectively included. The associations between baseline clinical characteristics, including NLR, and tumor response, progression and survival were investigated. RESULTS: Elevated NLR (≥3.5) was observed in 33 of 81 patients. The progression-free and overall survival of the patients with increased NLR was significantly worse than that of the patients with decreased NLR (8.20 vs 10.60 months, P < 0.001 and 17.20 vs 23.20 months, P < 0.001, respectively). Elevated NLR was confirmed to be an independent prognostic factor for worse progression-free and overall survival in Cox multivariate analysis. CONCLUSION: Elevated NLR is likely to be associated with poor outcome in EGFR-mutated advanced NSCLC patients treated with first-line EGFR TKIs.

PPy@MIL-100 Nanoparticles as a pH- and Near-IR-Irradiation-Responsive Drug Carrier for Simultaneous Photothermal Therapy and Chemotherapy of Cancer Cells.

A medical nanoplatform with small size, low cost, biocompatibility, good biodegradability, and, in particular, multifunctionality has attracted much attention in the exploration of novel therapeutic methodologies. As an emerging material of self-assembled porous structure, metal-organic frameworks (MOFs) have high expectations because of their special properties compared to traditional porous materials. Therefore, integration of MOFs and functional materials is leading to the creation of new multifunctional composites/hybrids. Photothermal therapy (PTT), using near-IR (NIR) laser-absorbing nanomaterials as PTT agents, has shown encouraging therapeutic effects to photothermally ablate tumors. However, the most of widely used PTT agents are inorganic materials and nonbiodegradable. Herein, uniform polypyrrole (PPy) nanoparticles (NPs) with good biodegradability were synthesized by a microemulsion method. The PPy NPs were further coated with the mesoporous iron-based MOF structure MIL-100 by interaction between PPy NPs and MIL-100 precursors at room temperature. As a multifunctional nanoplatform, an anticancer drug could easily be loaded into the mesopores of the MIL-100 shell. The PPy core, as an organic photothermal agent, is able to photothermally ablate cancer cells and improve the efficacy of chemotherapy under NIR irradiation. The composites showed an outstanding in vivo synergistic anticancer capacity. Our work could encourage further study in the construction of a synergetic system using MOFs and organic PTT agents.

Serum neuron-specific enolase levels are upregulated in patients with acute lymphoblastic leukemia and are predictive of prognosis.

We explored the relationship between neuron-specific enolase (NSE) levels and the clinical features of acute lymphoblastic leukemia (ALL). Seventy ALL patients and forty-two healthy controls were enrolled in this study, and their serum NSE levels were measured using an electrochemiluminescence assay. The serum NSE concentration was higher in ALL patients than in healthy controls. In ALL patients, the mean serum NSE level declined after complete remission (CR) but increased with relapse. In addition, the mean serum NSE level was lower in the CR group than in the non-CR group. High NSE levels were associated with poorer progression-free and overall survival than low NSE levels. Serum NSE levels closely correlated with several clinical features, including the immunophenotype, risk stratification and serum lactate dehydrogenase levels. Multivariate analysis revealed that high NSE expression was an independent prognostic factor in adult ALL patients. NSE mRNA levels were also higher in ALL cell lines and bone marrow mononuclear cells from ALL patients than in control cells. These results suggested that NSE could be a clinical prognostic factor and a potential therapeutic target in ALL.

A childhood chemotherapy protocol improves overall survival among adults with T-lymphoblastic lymphoma.

A broadly accepted standard treatment for adult T-lymphoblastic lymphoma (T-LBL) has not yet been defined. To address that issue, we retrospectively compared three chemotherapy regimens used to treat 110 adult patients with newly diagnosed T-LBL. These included two adult regimens (ECOG2993 and hyper-CVAD) and a childhood regimen (BFM-90). These intensive drug regimens are mainly used to treat childhood and adult acute lymphoblastic leukemia. They included induction, consolidation, and maintenance chemotherapy protocols and were administered over the course of 2 years. Seventy-five patients (80%) achieved a complete remission (CR). Within a median follow-up time of 31 months (range: 5-152 months), the 5-year overall survival (OS) and progression-free survival (PFS) rates were 47.7% (95% CI, 35.0-69.8%) and 45.7% (95% CI, 27.6-56.6%), respectively. Shorter survival was associated with age > 40 years, poor ECOG PS and bone marrow involvement. Elevated lactic dehydrogenase (LDH) level, Ann Arbor stage and International Prognostic Index (IPI) score had no prognostic value. The childhood chemotherapy regimen improved CR and the overall survival rate more than the adult regimen in patients aged < 40 years.

High level of interleukin-10 in serum predicts poor prognosis in multiple myeloma.

BACKGROUND: Interleukin-10 (IL-10) is a inhibiting inflammatory cytokine that plays an important role in immune suppressive microenvironment in multiple myeloma (MM). Whether the level of serum IL-10 could predict treatment response and survival outcomes or not needs to be investigated in MM patients. METHODS: The level of IL-10 in serum was measured using enzyme-linked immunosorbent assay in 188 patients with newly diagnosed MM. RESULTS: The best cutoff value for IL-10 in predicting survival is 169.69 pg ml(-1) with an area under the curve (AUC) value of 0.747 (P<0.001). In all, 92 patients (48.9%) were classified as high-IL-10 group (>169.96 pg ml(-1)) and 96 patients (51.1%) as low-IL-10 group (⩽169.96 pg ml(-1)). The overall response rate (ORR) was 79.2% in low-IL-10 group, significantly higher than that in high-IL-10 group (53.3%, P<0.001). Patients in low-IL-10 group had significantly better survival compared with those in high-IL-10 group (3-year PFS rate: 69.3% vs 13.3%, P<0.001; 3-year OS rate: 93.6% vs 51.9%, P<0.001). Multivariate analysis revealed that serum IL-10 level >169.96 pg ml(-1) at diagnosis and certain cytogenetic abnormalities were two adverse factors for PFS and OS. CONCLUSIONS: Our data suggest that serum IL-10 at diagnosis is a novel, powerful predictor of prognosis for MM.

First-line combination of GELOX followed by radiation therapy for patients with stage IE/IIE ENKTL: An updated analysis with long-term follow-up.

In recent years, asparaginase-based chemotherapy regimens have produced excellent short-term efficacy in patients with extranodal natural killer/T-cell lymphoma (ENKTL). However, few long-term outcomes have been reported to date. A phase II clinical trial evaluating the efficacy and safety of a combination of gemcitabine, oxaliplatin and asparaginase (GELOX), followed by radiotherapy (RT) in the treatment of localized ENKTL, was reported by this group in 2012. By the time of the present analysis, detailed information had been collected for all 27 patients in the phase II trial, over an extended follow-up period. The median follow-up time was 63.15 months. The 5-year overall survival and progression-free survival were 85.0 and 74.0%, respectively. Recurrence within the RT field was observed in three patients, and the planning target-volume control rate at 5 years was 88.9%. One patient with confirmed lung invasion who did not respond to autologus stem cell transplantation (ASCT) was successfully treated by salvage therapy with lenalidomide monotherapy, and the EBV DNA load in this individual reflected disease progression and treatment response. No clinically significant late toxicities were identified during follow-up visits. In conclusion, this updated analysis confirmed the long-term benefit of the GELOX regimen followed by RT, and demonstrated a good safety profile for this treatment. This strategy may be one of the most suitable options for the treatment of early stage ENKTL.

Serum levels of soluble programmed death ligand 1 predict treatment response and progression free survival in multiple myeloma.

Immune checkpoint signaling plays an important role in immunosuppression in multiple myeloma (MM). Blood levels of soluble programmed death-ligand 1 (sPD-L1), a checkpoint-relevant protein, might predict treatment response and survival outcomes in MM patients. We used an enzyme-linked immunosorbent assay to measure serum sPD-L1 levels in 81 newly diagnosed MM patients. We found that myeloma patients had higher sPD-L1 concentrations than healthy controls. The best sPD-L1 cutoff value for predicting disease progression risk was 2.783 ng/mL. The overall response rate to treatment was higher in low sPD-L1 patients than in high sPD-L1 patients. The 3-year progression free survival (PFS) and overall survival (OS) rates for all patients were 16% and 64%, respectively. Multivariate survival analysis including Eastern Cooperative Oncology Group performance status score, treatment response, and sPD-L1 level showed that a less than partial treatment response (PR) and higher sPD-L1 levels (>2.783 ng/ml) were independent prognostic factors for shorter PFS; neither factor was predictive of OS. The serum sPD-L1 level is a valuable biomarker for predicting treatment response and an independent prognostic factor for PFS. PD-1/ PD-L1 blockade may be a promising novel immune-based therapeutic strategy in MM.

Once-weekly subcutaneous administration of bortezomib in patients with multiple myeloma.

In patients with multiple myeloma (MM), once-weekly intravenous injection or twice-weekly subcutaneous injection (SC) of bortezomib has been proven to offer non-inferior efficacy to standard twice-weekly intravenous administration, with an improved safety profile. However, whether once-weekly SC bortezomib can further reduce the incidence rate of peripheral neuropathy (PN) and not compromise the efficacy remains to be investigated. 25 patients of MM treated with once-weekly SC bortezomib were reviewed in this study. The median treatment cycles were 4 (range, 2-9 cycles). Complete response (CR) rate was 52%, ≥very good partial response (VGPR) rate was 72%, and ≥partial response (PR) rate was 84%. 1-year and 2-year PFS rate was 63.0% and 34.3%, respectively, and 2-year OS rate was 100%. Any grade of PN was reported in 9 patients (36.0%), with 7 patients (28.0%) had grade 1 PN, and 2 patients (8.0%) had grade 2 PN. No patients reported grade 3/4 PN in this cohort. In conclusion, once-weekly subcutaneous administration of bortezomib offers excellent efficacy with a further improved safety profile, especially with regard to PN. It needs to be validated in future prospective randomized trials.

A prognostic model to predict survival in stage III colon cancer patients based on histological grade, preoperative carcinoembryonic antigen level and the neutrophil lymphocyte ratio.

BACKGROUND: Stage III colon cancer patients demonstrate diverse clinical outcomes. The aim of this study was to develop a prognostic model in order to better predict their survival. MATERIALS AND METHODS: From 2004 to 2010, 548 patients were retrospectively analyzed, among whom 328 were defined as the study group and the remaining 220 served as a validation group. Clinico-pathologic features, including age, gender, histological grade, T stage, number of positive lymph nodes, number of harvest lymph nodes, pretreatment carcinoembryonic antigen (CEA) levels and pretreatment neutrophil lymphocyte ratio (NLR), were collected. Kaplan-Meier survival curves were used to detect prognostic factors and multivariate analysis was applied to identify independent examples on which to develop a prognostic model. Finally, the model was further validated with the validation group. RESULTS: Histological grade (p=0.002), T stage (p=0.011), number of positive lymph nodes (p=0.003), number of harvested lymph nodes (p=0.020), CEA (p=0.005), and NLR (p<0.001) were found as prognostic factors while histological grade [RR(relative risk):0.632, 95%CI (Confidence interval) 0.405~0.985, p=0.043], CEA (RR:0.644, 95%CI:0.431~0.964, p=0.033) and NLR (RR:0.384, 95%CI:0.255~0.580, p<0.001) levels were independent. The prognostic model based on these three factors was able to classify patients into high risk, intermediate and low risk groups (p<0.001), both in study and validation groups. CONCLUSIONS: Histological grade, pretreatment CEA and NLR levels are independent prognostic factors in stage III colon cancer patients. A prognostic model based on these factors merits attention in future clinical practice.

Hepatitis B virus infection correlates with poor prognosis of extranodal natural killer/T cell lymphoma.

Studies have shown that hepatitis B virus (HBV) infection may play an important role in the lymphomagenesis of lymphoma, but no studies regarding the relationship between HBV infection and extranodal natural killer/T cell lymphoma (ENKTL) have been reported previously. One hundred and seven patients diagnosed with ENKTL were retrospectively reviewed. The hepatitis B surface antigen (HBsAg)-positive rate was 13.1%, and no significant correlation existed between HBV infection and clinical characteristics (p > 0.05). No significant difference existed in complete remission rate between HBsAg-positive and -negative groups (42.9% vs. 44.1%, p = 1.000). In a multivariate Cox regression model that included international prognostic index (IPI) score, induction chemotherapy regimen and HBsAg status, all these variables were independent prognostic factors for overall survival (OS) and progression-free survival (PFS) (p < 0.05). In conclusion, the HBsAg-positive rate in ENKTL was similar to that of the normal population in a high HBV endemic area, and HBsAg-positive status was an independent prognostic factor for OS and PFS.