Proteomic and meta-transcriptomic study on lymph node metastasis in gastric cancer

AbstractTo examine the proteomic background of lymph node metastasis (LNM) in gastric cancer, we performed protein expression profiling of paired non-tumor, primary tumor, and LNM tissues. Using a label-free proteomic approach, we generated protein expression profiles of 3894 unique proteins and identified 109 differentially expressed proteins. Functional pathway analysis of the differentially expressed proteins showed that members of the beta-3 integrin (ITGB3) pathway were significantly enriched. Aberrations of ITGB3 were reported in various malignancies; however, ITGB3 in LNM tissues has not been examined to date. Different level of ITGB3 expression was confirmed in 20 gastric cancer cases by Western blotting. We analyzed the mRNA levels of the differentially expressed proteins by using a public mRNA expression database; 38.8% of the proteins examined, including those involved in oxidation and reduction, showed correlation between protein and mRNA levels. Proteins without such correlation included factors related to cell adhesion. Our study suggests a novel role for the integrin pathway in the development of LNM in gastric cancer and indicated possible benefits of observational transcriptomic analysis for proteomic studies

Elevated C-reactive protein associates with early-stage carotid atherosclerosis in young subjects with type 1 diabetes

WSTĘP. Celem badania była ocena wpływu procesu zapalnego o małym nasileniu na wczesną fazę rozwoju zaawansowanej miażdżycy tętnic szyjnych u młodych chorych na cukrzycę typu 1. MATERIAŁ I METODY. U 55 chorych na cukrzycę typu 1 (22 mężczyzn i 33 kobiety, w wieku 22,1 &plusmn; 3,6 lat (&plusmn; SD), z cukrzycą trwającą 14,2 &plusmn; 5,7 lat) oraz u 75 osób bez cukrzycy z tej samej grupy wiekowej (28 mężczyzn i 47 kobiet) wykonano pomiar średniej i maksymalnej grubości kompleksu błony wewnętrznej i środkowej (IMT, intima-media thickness) w tętnicy szyjnej przy użyciu ultrasonograficznej prezentacji B. Stężenie białka C-reaktywnego dużej czułości (hs-CRP, high-sensitive C-reactive protein) oznaczano za pomocą immunonefelometru z zastosowaniem lateksu. WYNIKI. U chorych na cukrzycę typu 1 stężenie hs-CRP (mediana 0,35, zakres 0,05&#8211;1,47 mg/l u chorych na cukrzycę; mediana 0,14, zakres 0,05&#8211;1,44 mg/l u osób bez cukrzycy; p = 0,001) oraz średnia i maksymalna IMT (średnia IMT 0,76 &plusmn; 0,09 vs. 0,72 &plusmn; 0,04 mm, p = 0,003; maksymalna IMT 0,84 &plusmn; 0,11 vs. 0,77 &plusmn; 0,06, p < 0,0001) były wyraźnie większe niż u osób bez cukrzycy. Stężenie hs-CRP wykazywało wyraźną zależność ze średnią i maksymalną IMT u chorych na cukrzycę typu 1 oraz z maksymalną IMT u osób bez cukrzycy. Analiza metodą regresji wielowymiarowej przeprowadzona łącznie dla grupy chorych na cukrzycę oraz osób bez cukrzycy wykazała, że stężenie hs-CRP niezależnie koreluje ze średnią oraz maksymalną IMT (odpowiednio: p = 0,002 i p = 0,023), jak również z rozkurczowym ciśnieniem tętniczym, płcią i czasem trwania cukrzycy. WNIOSKI. Dane uzyskane w badaniu wskazują, że u młodych chorych na cukrzycę typu 1 stężenie hs- -CRP jest podwyższone, co może mieć związek z wczesną fazą rozwoju zaawansowanej miażdżycy tętnic szyjnych.INTRODUCTION. To evaluate whether low-grade inflammation contributes to early-stage advanced carotid atherosclerosis in young subjects with type 1 diabetes. MATERIAL AND METHODS. The mean and maximum (max) intima-media thicknesses (IMT) of the carotid artery were assessed using ultrasound B-mode imaging in 55 patients with type 1 diabetes (22 men and 33 women, aged 22.1 &#177; 3.6 years (&#177; SD), duration of diabetes 14.2 &#177; 5.7 years) and 75 age-matched healthy nondiabetic subjects (28 men and 47 women). High-sensitive C-reactive protein (hs-CRP) levels were measured with a latex-enhanced immunonephelometer. RESULTS. The patients with type 1 diabetes had significantly higher hs-CRP levels (median 0.35, range 0.05&#8211;1.47 mg/l vs. median 0.14, range 0.05&#8211;1.44 mg/l; P = 0.001) as well as significantly higher mean IMT and max IMT than the nondiabetic subjects (mean IMT 0.76 &#177; 0.09 vs. 0.72 &#177; 0.04 mm, P = 0.003; max IMT 0.84 &#177; 0.11 vs. 0.77 &#177; 0.06 mm, P < 0.0001). Hs-CRP levels were significantly correlated with the mean and max IMT of patients with type 1 diabetes and with the max IMT of nondiabetic patients. Multivariate regression analyses for both diabetic and nondiabetic subjects as a single group showed that hs-CRP levels are independently correlated with the mean IMT and max IMT levels (P = 0.002 and P = = 0.023, respectively) as well as with diastolic blood pressure, sex, and duration of diabetes. CONCLUSIONS. Our data indicate that hs-CRP levels are elevated in young patients with type 1 diabetes, possibly corresponding with early-stage advanced carotid atherosclerosis

Real-world effectiveness and safety analysis of carfilzomib-lenalidomide-dexamethasone and carfilzomib-dexamethasone in relapsed/refractory multiple myeloma: a multicenter retrospective analysis

Background: Little is known about the real-world survival benefits and safety profiles of carfilzomib-lenalidomide-dexamethasone (KRd) and carfilzomib-dexamethasone (Kd). Methods: We performed a retrospective analysis to evaluate their efficacy and safety in 157 patients registered in the Kansai Myeloma Forum database. Results: A total of 107 patients received KRd. Before KRd, 99% of patients had received bortezomib (54% were refractory disease), and 82% had received lenalidomide (57% were refractory disease). The overall response rate (ORR) was 68.2%. The median progression-free survival (PFS) and overall survival (OS) were 8.8 and 29.3 months, respectively. Multivariate analysis showed that reduction of the carfilzomib dose and non-IgG M protein were significantly associated with lower PFS and reduction of the carfilzomib dose and refractoriness to prior bortezomib-based regimens were significantly associated with lower OS. A total of 50 patients received Kd. Before Kd, 96% of patients had received bortezomib (54% were refractory disease). The ORR was 62.0%. The median PFS and OS were 7.1 and 20.9 months, respectively. Based on the multivariate analysis, reduction of the carfilzomib dose and International Staging System Stage III (ISS III) were significantly associated with lower PFS. Grade III or higher adverse events were observed in 48% of KRd cases and 54% of Kd cases. Cardiovascular events, cytopenia, and infections were frequent, and 4 KRd patients died due to heart failure, arrhythmia, cerebral hemorrhage, and pneumonia. Conclusion: Our analysis showed that an adequate dose of carfilzomib is important for achieving the best survival benefits in a real-world setting. Adverse effects after KRd and Kd therapy should also be considered

Monocyte or white blood cell counts and β₂ microglobulin predict the durable efficacy of daratumumab with lenalidomide

BACKGROUND: Daratumumab is one of the most widely used treatments for relapsed/refractory multiple myeloma (MM) patients. However, not all patients achieve a lasting therapeutic response with daratumumab. OBJECTIVES: We hypothesized that a durable response to daratumumab could be predicted by the balance between the MM tumor burden and host immune status. DESIGN: We conducted a retrospective study using the real-world data in the Kansai Myeloma Forum (KMF) database. METHODS: We retrospectively analyzed 324 relapsed/refractory MM patients who were treated with daratumumab in the KMF database. RESULTS: In this study, 196 patients were treated with daratumumab, lenalidomide, and dexamethasone (DLd) regimen and 128 patients were treated with daratumumab, bortezomib, and dexamethasone (DBd) regimen. The median age at treatment, number of prior treatment regimens and time-to-next-treatment (TTNT) were 68, 4 and 8.02 months, respectively. A multivariate analysis showed that the TTNT under the DLd regimen was longer with either higher monocyte counts (analysis 1), higher white blood cell (WBC) counts (analysis 2), lower β2 microglobulin (B2MG < 5.5 mg/L) or fewer prior regimens (<4). No parameters were correlated with TTNT under the DBd regimen. CONCLUSION: We propose a simple scoring model to predict a durable effect of the DLd regimen by classifying patients into three categories based on either monocyte counts (0 points for ⩾200/μl; 1 point for <200/μl) or WBC counts (0 points for ⩾3500/μl; 1 point for <3500/μl) plus B2MG (0 points for <5.5 mg/L; 1 point for ⩾5.5 mg/L). Patients with a score of 0 showed significantly longer TTNT and significantly better survival compared to those with a score of 1 or 2 (both p < 0.001). To confirm this concept, our results will need to be validated in other cohorts

Is Early Enteral Nutrition Better for Postoperative Course in Esophageal Cancer Patients?

We retrospectively examined esophageal cancer patients who received enteral nutrition (EN) to clarify the validity of early EN compared with delayed EN. A total of 103 patients who underwent transthoracic esophagectomy with three-field lymphadenectomy for esophageal cancer were entered. Patients were divided into two groups; Group E received EN within postoperative day 3, and Group L received EN after postoperative day 3. The clinical factors such as days for first fecal passage, the dose of postoperative albumin infusion, differences of serum albumin value between pre- and postoperation, duration of systematic inflammatory response syndrome (SIRS), incidence of postoperative infectious complication, and use of total parenteral nutrition (TPN) were compared between the groups. The statistical analyses were performed using Mann-Whitney U test and Chi square test. The statistical significance was defined as p &lt; 0.05. Group E showed fewer days for the first fecal passage (p &lt; 0.01), lesser dose of postoperative albumin infusion (p &lt; 0.01), less use of TPN (p &lt; 0.01), and shorter duration of SIRS (p &lt; 0.01). However, there was no significant difference in postoperative complications between the two groups. Early EN started within 3 days after esophagectomy. It is safe and valid for reduction of albumin infusion and TPN, for promoting early recovery of intestinal movement, and for early recovery from systemic inflammation

Is Early Enteral Nutrition Better for Postoperative Course in Esophageal Cancer Patients?

We retrospectively examined esophageal cancer patients who received enteral nutrition (EN) to clarify the validity of early EN compared with delayed EN. A total of 103 patients who underwent transthoracic esophagectomy with three-field lymphadenectomy for esophageal cancer were entered. Patients were divided into two groups; Group E received EN within postoperative day 3, and Group L received EN after postoperative day 3. The clinical factors such as days for first fecal passage, the dose of postoperative albumin infusion, differences of serum albumin value between pre- and postoperation, duration of systematic inflammatory response syndrome (SIRS), incidence of postoperative infectious complication, and use of total parenteral nutrition (TPN) were compared between the groups. The statistical analyses were performed using Mann-Whitney U test and Chi square test. The statistical significance was defined as p < 0.05. Group E showed fewer days for the first fecal passage (p < 0.01), lesser dose of postoperative albumin infusion (p < 0.01), less use of TPN (p < 0.01), and shorter duration of SIRS (p < 0.01). However, there was no significant difference in postoperative complications between the two groups. Early EN started within 3 days after esophagectomy. It is safe and valid for reduction of albumin infusion and TPN, for promoting early recovery of intestinal movement, and for early recovery from systemic inflammation

Gastric cancer surgery for patients with liver cirrhosis

AIM: To elucidate the influence of liver cirrhosis (LC) on the prognosis of patients with gastric cancer (GC)