Exploring the role of lactylation-related genes in osteosarcoma: A deep dive into prognostic significance and therapeutic potential.

Osteosarcoma (OS), notorious for its complex pathogenesis and formidable prognosis, represents a significant medical quandary. This research embarked on a quest to unravel the implications of lactylation-related genes (LRGs) in OS, offering a novel lens through which to interpret its intricacies. A meticulous evaluation of 329 LRGs within the TARGET dataset spotlighted 27 paramount genes, intricately intertwined with survival. These genes highlighted metabolic processes-particularly amino acid metabolism-as key players, as evidenced in both GO and KEGG analyses. Utilizing consensus clustering and principal component analysis, the 93 OS samples were segmented into two distinct groups, differing notably in overall and event-free survival. Cluster 2 demonstrated a heightened immune response, contrasting the other cluster. Machine learning techniques, like generalized boosted model, CoxBoost, and RSF, spotlighted MYC and GOT2 as critical genes. Using multivariate Cox regression, a risk model was developed, categorizing patients into high and low-risk groups, each displaying varied survival patterns. Additionally, a contrast was observed between MYC and GOT2's associations with HLA molecules, emphasizing their distinct roles in antigen presentation. Potential therapeutic avenues were identified for each risk group, with special attention to mutations in MYC, particularly amplifications, hinting at its role in tumor progression. Finally, delving deeper into the role of MYC, Western blot analyses exhibited amplified myc protein levels in OS cells U-2 and MG-63 when juxtaposed against human osteoblastic cells Hfob1.19. A focused knockdown of myc in OS cells subsequently confirmed its influence on cell proliferation and migration, with reduced myc expression resulting in inhibited cell activities. Furthermore, immunofluorescence assays corroborated myc's heightened expression in OS cells relative to normal osteoblastic cells. In summary, this study accentuates the vital role of LRGs and specifically MYC in OS, ushering in a horizon of tailored therapeutic strategies.

TLR2 promotes development and progression of human glioma via enhancing autophagy.

OBJECTIVE: In this study, we aim to evaluate Toll-like receptor 2 (TLR2) expression in human glioma tumors and the correlation between its expression with degrees of malignancy and autophagy, development of tumors. METHOD: Immunohistochemistry and Western blot were carried out to determine the expression of LC3, Beclin1 and TLR2 in 74 glioma specimens. We analyzed the prognosis of 551 glioma patients through the Cancer Genome Atlas (TCGA). To determine the effect of TLR2 in glioma, we manipulated TLR2 expression using TLR2 plasmid transfer technique in U87 human glioma cell. RESULTS: TLR2 expression in high-grade was significantly higher than that in low-grade glioma group (P < 0.05). TLR2 was positively correlated with tumor grade (P < 0.05). Spearman correlation showed that the expression of TLR2 was positively correlated with the numbers of LC3 and Beclin1 (P < 0.05). The patients with high TLR2 expression had a poorer outcome compared with the patients with low TLR2 in low-grade glioma (P < 0.05). TLR2 overexpression enhances glioma cell activity and accelerates cell cycle progression. In addition, treatment with TLR2 overexpression increases the conversion rate of LC3-I to LC3-II and enhances the level of phosphorylated p38. CONCLUSION: TLR2 promotes development and progression of human glioma via enhancing autophagy.

[A randomized trial comparing oxaliplatin plus vinorelbine versus cisplatin plus vinorelbine for the treatment of patients with advanced non-small-cell lung cancer].

OBJECTIVE: To evaluate the difference of efficacy, side-effects and quality of life in advanced non-small-cell lung cancer (NSCLC) patients treated with oxaliplatin plus vinorelbine or cisplatin plus vinorelbine. METHODS: Eligible patients were randomly assigned to NL (oxaliplatin + vinorelbine) group and NP (cisplatin + vinorelbine) group in a 2:1 ratio. In the NL group, 70 evaluable cases were treated with oxaliplatin 130 mg/m(2) i.v. on day 2, and vinorelbine 25 mg/m(2) i.v. on days 1 and 8 in 21 days per cycle. In the NP group, 32 evaluable cases were treated with cisplatin 80 mg/m(2) i.v. divided to 2 - 3 days dosing, 21 days per cycle, and vinorelbine administered by the same way as in the NL group. The response rate, time to progression (TTP), one-year survival, side-effects and the quality of life were observed. RESULTS: The response rate was 35.7% vs. 43.8% (P = 0.4), median TTP was 4.7 months vs. 5.5 months (P = 0.6), one-year survival rate was 38.5% vs. 58.6% (P = 0.07) in the NL and NP groups, respectively. Grade I-II neuro-sensory toxicity occurred significantly more frequent in NL group than in NP group (68.4% vs. 36.4%, P = 0.0017). However, Grade I-II granulocytopenia was significantly less occurred in NL group than in NP group (49.4% vs. 70.6%, P = 0.037). There was no statistically difference between the two groups regarding quality of life. CONCLUSION: Due to good efficacy and tolerability, the NL regimen offered a new candidate for treating advanced NSCLC.

[Combination of EP regimen and split-course hyperfractionated accelerated irradiation in locally advanced non-small cell lung cancer].

BACKGROUND: To investigate the efficacy of EP regimen combined with split-course hyperfractionated accelerated irradiation for locally advanced non-small cell lung cancer. METHODS: The treatment was composed of 3 cycles of combined chemoradiotherapy at 4-week intervals. Chemotherapy with cisplatin ( 30 mg/m²) and etoposide (60 mg/m²) was administrated intravenously on days 1-3, followed by radiotherapy on days 4-8. A course of radiotherapy consisted of 1.5 Gy per fraction, twice a day (3 Gy per day) for 5 consecutive days, for a total dose of 15 Gy. In the third cycle, additional irradiotherapy consisted of 2 Gy once a day was performed on days 11-15, for a total dose up to 55 Gy during 10 weeks. After three cycles, patients were given 2 additional cycles of chemotherapy with MVP regimen. RESULTS: Of the 43 patients, 12 had a complete remission and 22 a partial response, resulting in an overall response rate of 79.1%. Of the 152 chemotherapeutic cycles administrated, there were 40 during which grade III-IV toxicities occurred, mainly consisting of leukopenia and vomiting. The 1- and 2-year survival rates were 66.7% and 57.2%, respectively. CONCLUSIONS: EP regimen combined with split-course hyperfractionated accelerated irradiation is effective and well tolerated for advanced locally non-small celll lung cancer. It should be investigated further.

Evidence that tilapia islets do not express alpha-(1,3)gal: implications for islet xenotransplantation.

BACKGROUND: Cell therapy for diabetes using teleost fish islet tissue has emerged as an intriguing alternative to the use of islet tissue from mammalian pancreases. The islet tissue, called Brockman bodies (BBs), is anatomically distinct from the pancreatic exocrine tissue and can be easily identified and isolated. Islets harvested from Nile tilapia (Oreochromis niloticus), when transplanted into streptozotocin-diabetic nude mice, produce long-term normoglycemia and achieve mammalian-like glucose tolerance profiles. We asked whether tilapia express the alpha-(1,3)gal epitope, the immunodominant target of human xenogeneic responses. METHODS AND RESULTS: Immunostaining with the alpha-(1,3)gal-specific IB4 lectin on tilapia BB, liver, heart, spleen, and head kidney was negative, as was staining with murine anti-alpha-gal-specific monoclonal antibodies. Absence of alpha-gal-specific binding of IB4 or murine anti-gal mAbs to dispersed BBs was confirmed by fluorescent-activated cell sorter analysis. Tilapia BB cell membranes failed to reduce binding of anti-alpha-(1,3)gal-specific mAb in an enzyme-linked immunosorbent assay (ELISA) inhibition assay, while porcine and murine tissue lysates did. Tilapia BB cell lysates were shown to be devoid of alpha-1,3 galactosyltransferase activity by ELISA. Transplantation of tilapia BBs into diabetic alpha-gal knockout (gal KO) mice was not associated with accelerated xenograft rejection when compared with wild type control recipients (mean survival time 6.5 days vs. 7.2 days). Tilapia BBs failed to induce a rise in anti-gal IgG and IgM titers in gal KO mice, while the transplant of wild type mouse islets into gal KO mice caused a significant rise in anti-gal IgG and IgM antibodies. CONCLUSIONS: We conclude that tilapia BBs are devoid of alpha-gal expression, and may offer an alternative to swine as a donor species for islet xenotransplantation.