Bone structural and metabolic response of caloric restriction in Wistar rats and a GH-IGF-1 axis-suppressed transgenic rat model.

The growth hormone?insulin-like growth factor-1 (GH?IGF-1) axis plays an important role in the effects of caloric restriction(CR) on lifespan extension and may elicit effects on bone metabolism in CR animals. We compared the effects of the GH?IGF-1 axis suppression and CR on bone metabolism. We used Wistar rats fed ad libitum (control group) or fed a 30% calorierestricted diet in CR group and heterozygous transgenic (F1) rats whose GH-IGF-1 axis is moderately suppressed. There was no significant difference in serum IGF-1 concentration between control and CR rats; however, IGF-1 was significantly lower inF1 rats than in other groups. The bone volume fraction (BV/TV) was significantly lower in CR than in the control. The mean SMI value in CR rats was marginally significant difference from that in control rats, Although there was no difference in serum IGF-1 concentrations between CR and control rats, bone volume was lower, and higher SMI was observed in the former. The serum IGF-1 levels in F1 rats were lower than those of controls, but the bone volume and SMI in F1 were not different. Therefore, the effects of bone metabolism in CR rats may be different from those in the GH-IGF-1 suppression rats

Bone structural and metabolic response of caloric restriction in Wistar rats and a GH-IGF-1 axis-suppressed transgenic rat model.

The growth hormone–insulin-like growth factor-1 (GH–IGF-1) axis plays an important role in the effects of caloric restriction (CR) on lifespan extension and may elicit effects on bone metabolism in CR animals. We compared the effects of the GH–IGF-1 axis suppression and CR on bone metabolism. We used Wistar rats fed ad libitum (control group) or fed a 30% calorierestricted diet in CR group and heterozygous transgenic (F1) rats whose GH-IGF-1 axis is moderately suppressed. There was no significant difference in serum IGF-1 concentration between control and CR rats; however, IGF-1 was significantly lower in F1 rats than in other groups. The bone volume fraction (BV/TV) was significantly lower in CR than in the control. The mean SMI value in CR rats was marginally significant difference from that in control rats, Although there was no difference in serum IGF-1 concentrations between CR and control rats, bone volume was lower, and higher SMI was observed in the former. The serum IGF-1 levels in F1 rats were lower than those of controls, but the bone volume and SMI in F1 were not different. Therefore, the effects of bone metabolism in CR rats may be different from those in the GH-IGF-1 suppression rats

Predictive impact of C-reactive protein to albumin ratio for recurrent or metastatic head and neck squamous cell carcinoma receiving nivolumab

Abstract Although the neutrophil to lymphocyte ratio (NLR) was reported to be a predictive biomarker for clinical outcomes in various types of cancer, including recurrent or metastatic head and neck cancer (R/M HNSCC) treated with nivolumab, the usefulness of the pretreatment C-reactive protein/albumin ratio (CAR) as a prognostic marker remains to be clarified. This study aimed to analyze the clinical usability of the CAR in comparison with that of the NLR. 46 R/M HNSCC patients treated with nivolumab were retrospectively analyzed. The optimal cutoff value for the CAR was calculated using receiver operating characteristic curve analysis. The optimal cutoff value for the CAR was set to 0.30. On multivariate analyses, a high CAR was significantly associated with poor overall survival (adjusted HR, 2.19; 95% CI, 1.42–3.47; p < 0.01) and progression-free survival (adjusted HR, 1.98; 95% CI, 1.38–2.80; p < 0.01). The overall response rate and disease control rate for the high CAR patients were lower than for the low CAR patients. The CAR had significantly higher area under the curve values than the NLR at 2 and 4 months. The pretreatment CAR might be an independent marker for prognosis and efficacy in R/M HNSCC patients treated with nivolumab

Nanoliposomal irinotecan with fluorouracil and folinic acid, FOLFIRINOX, and S-1 as second-line treatment for unresectable pancreatic cancer after gemcitabine/nab-paclitaxel

Abstract This study aimed to compare second-line treatment outcomes for patients with unresectable pancreatic cancer previously treated with gemcitabine plus nab–paclitaxel (GnP) therapy. We conducted an integrated analysis of two retrospective studies included 318 patients receiving nanoliposomal irinotecan + 5-fluorouracil/folinic acid (NFF) (n = 102), S-1 (n = 57), or FOLFIRINOX (n = 14) as second-line treatment. Median overall survival (OS) in the NFF group was 9.08 months, significantly better than S-1 (4.90 months, P = 0.002). FOLFIRINOX had a median OS of 4.77 months, not statistically different from NFF. Subgroup analyses of OS indicated NFF was generally superior, however, a statistical interaction was observed between the treatment regimen in serum Alb < 3.5 g/dL (P = 0.042) and serum CRP ≥ 0.3 mg/dL (P = 0.006). Median progression-free survival (PFS) was 2.93 months for NFF, significantly better than S-1 (2.53 months, P = 0.024), while FOLFIRINOX had a comparable PFS (3.04 months, P = 0.948). Multivariate analysis identified the serum CRP, serum CA19-9, duration of first-line GnP therapy, and use (yes/no) of S-1 for second-line treatment as independent predictors for OS. This study concludes that second-line NFF therapy demonstrated a more favorable OS compared to S-1 therapy, however, it is still important to consider the patient background characteristics while selecting the most appropriate treatment

Effect of 1-week treatment with erythropoietin on the vascular endothelial function in anaesthetized rabbits

1. Chronic administration of erythropoietin (EPO) is often associated with hypertension in animals and humans. The aim of this study was to estimate whether 1-week treatment with EPO can affect the vascular endothelial function. 2. Rabbits were given with EPO (400 iu kg(−1) s.c.) or saline each other day for 1 week. Hypotensive responses to intravenously given acetylcholine (ACh), endothelium-independent nitric oxide donors (NOC7, nitroprusside and nitroglycerin) and prostaglandin I(2) were tested before and after administration of N(G)-nitro-L-arginine methyl ester (L-NAME), a specific nitric oxide synthase inhibitor, under pentobarbitone anaesthesia. 3. Blood haemoglobin concentration in EPO group was significantly higher than that in control group, whereas baseline values of aortic pressure, heart rate and femoral vascular resistance were similar. The dose of ACh (172 ng kg(−1)) requiring for a 15 mmHg hypotension from the baseline in EPO group was apparently higher than that (55 ng kg(−1)) in control group. On the contrary, hypotensive responses to NOC7, nitroprusside, nitroglycerin and prostaglandin I(2) were comparable between two groups. The extent of ACh-induced hypotension did not correlate with haemoglobin concentration. 4. L-NAME significantly inhibited the ACh-induced vasodilating response in control group but did not in EPO group. 5. In another set of rabbits, the same treatment with EPO also decreased vasodilating responses to carbachol, bradykinin and substance P besides ACh as compared with control group. 6. These results indicate that 1-week treatment with EPO selectively attenuates depressor responses to endothelium-dependent vasodilators in anaesthetized rabbits, most likely due to inhibition of endothelial nitric oxide synthase

Survival outcomes including salvage therapy of adult head and neck para-meningeal rhabdomyosarcoma: a multicenter retrospective study from Japan

Abstract Background Rhabdomyosarcoma is the most common soft tissue sarcoma in children, but rare in adults. Para-meningeal rhabdomyosarcoma in head and neck (PM-HNRMS) is less applicable for surgery due to the anatomic reason. PM-HNRMS has a poor prognosis in children. However, its clinical outcomes remain unclear in adults due to the rarity. Further, there is almost no detailed data about salvage therapy. Methods We retrospectively examined the adult patients with PM-HNRMS treated at institutions belonging to the Kyushu Medical Oncology Group from 2009 to 2022. We evaluated the overall survival (OS) and progression-free survival (PFS) of the patients who received a first-line therapy. We also reviewed the clinical outcomes of patients who progressed against a first-line therapy and received salvage therapy. Results Total 11 patients of PM-HNRMS received a first-line therapy. The characteristics were as follows: median age: 38 years (range 25 – 63 years), histology (alveolar/spindle): 10/1, and risk group (intermediate/high): 7/4. As a first-line therapy, VAC and ARST0431-based regimen was performed in 10 and 1 patients, respectively. During a first-line therapy, definitive radiation for all lesions were performed in seven patients. The median PFS was 14.2 months (95%CI: 6.0 – 25.8 months): 17.1 months (95%CI: 6.0 – not reached (NR)) for patients with stage I-III and 8.5 months (95%CI: 5.2 – 25.8 months) for patients with stage IV. The 1-year and 3-year PFS rates were 54.5% and 11.3% for all patients. Median OS in all patients was 40.8 months (95%CI: 12.1 months–NR): 40.8 months (95%CI: 12.1 – NR) for patients with stage I-III and NR for patients with stage IV. The 5-year OS rate was 48.5% for all patients. Among seven patients who received salvage therapy, three are still alive, two of whom remain disease-free for over 4 years after completion of the last therapy. Those two patients received multi-modal therapy including local therapy for all detected lesions. Conclusion The cure rate of adult PM-HNRMS is low in spite of a first-line therapy in this study. Salvage therapy might prolong the survival in patients who received the multi-modal therapy including local therapy for all detected lesions