ABSTRACT
Intravesical chemotherapy is an important part of the treatment for superficial bladder cancer. However, the response to it is limited and its side effects are extensive. Functional single-walled carbon nanotubes (SWNT) have shown promise for tumor-targeted accumulation and low toxicity. In the present study, we performed in vivo and in vitro investigations to determine whether SWNT-based drug delivery could induce high tumor depression in rat bladder cancer and could decrease the side effects of pirarubicin (tetrahydropyranyl-adriamycin, THP). We modified SWNT with phospholipid-branched polyethylene glycol and constructed an SWNT-THP conjugate via a cleavable ester bond. The cytotoxicity of SWNT-THP against the human bladder cancer cell line BIU-87 was evaluated in vitro. Rat bladder cancer in situ models constructed by N-methyl-N-nitrosourea intravesical installation (1 g/L, 2 mg/rat once every 2 weeks for 8 weeks) were used for in vivo evaluation of the cytotoxicity of SWNT and SWNT-THP. Specific side effects in the THP group including urinary frequency (N = 12), macroscopic hematuria (N = 1), and vomiting (N = 7) were identified; however, no side effects were observed with SWNT-THP treatment. Flow cytometry was used to assess the cytotoxicity in vitro and in vivo. Results showed that SWNT alone did not yield significant tumor depression compared to saline (1.74 ± 0.56 and 1.23 ± 0.42%) in vitro. SWNT-THP exhibited higher tumor depression than THP-saline in vitro (74.35 ± 2.56 and 51.24 ± 1.45%) and in vivo (52.46 ± 2.41 and 96.85 ± 0.85%). The present findings indicate that SWNT delivery of THP for the treatment of bladder cancer leads to minimal side effects without loss of therapeutic efficacy. Therefore, this nanotechnology may play a crucial role in the improvement of intravesical treatment of bladder cancer.
Subject(s)
Animals , Female , Humans , Rats , Antineoplastic Agents/administration & dosage , Doxorubicin/analogs & derivatives , Nanotubes, Carbon , Urinary Bladder Neoplasms/drug therapy , Administration, Intravesical , Antineoplastic Agents/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Rats, Sprague-DawleyABSTRACT
Intravesical chemotherapy is an important part of the treatment for superficial bladder cancer. However, the response to it is limited and its side effects are extensive. Functional single-walled carbon nanotubes (SWNT) have shown promise for tumor-targeted accumulation and low toxicity. In the present study, we performed in vivo and in vitro investigations to determine whether SWNT-based drug delivery could induce high tumor depression in rat bladder cancer and could decrease the side effects of pirarubicin (tetrahydropyranyl-adriamycin, THP). We modified SWNT with phospholipid-branched polyethylene glycol and constructed an SWNT-THP conjugate via a cleavable ester bond. The cytotoxicity of SWNT-THP against the human bladder cancer cell line BIU-87 was evaluated in vitro. Rat bladder cancer in situ models constructed by N-methyl-N-nitrosourea intravesical installation (1 g/L, 2 mg/rat once every 2 weeks for 8 weeks) were used for in vivo evaluation of the cytotoxicity of SWNT and SWNT-THP. Specific side effects in the THP group including urinary frequency (N = 12), macroscopic hematuria (N = 1), and vomiting (N = 7) were identified; however, no side effects were observed with SWNT-THP treatment. Flow cytometry was used to assess the cytotoxicity in vitro and in vivo. Results showed that SWNT alone did not yield significant tumor depression compared to saline (1.74 ± 0.56 and 1.23 ± 0.42%) in vitro. SWNT-THP exhibited higher tumor depression than THP-saline in vitro (74.35 ± 2.56 and 51.24 ± 1.45%) and in vivo (52.46 ± 2.41 and 96.85 ± 0.85%). The present findings indicate that SWNT delivery of THP for the treatment of bladder cancer leads to minimal side effects without loss of therapeutic efficacy. Therefore, this nanotechnology may play a crucial role in the improvement of intravesical treatment of bladder cancer.
Subject(s)
Antineoplastic Agents/administration & dosage , Doxorubicin/analogs & derivatives , Nanotubes, Carbon , Urinary Bladder Neoplasms/drug therapy , Administration, Intravesical , Animals , Antineoplastic Agents/adverse effects , Doxorubicin/administration & dosage , Doxorubicin/adverse effects , Female , Humans , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Research on children's loneliness has been conducted mostly in Western, especially North American, cultures. The purpose of the study was to examine relations between loneliness and social adaptation among children and adolescents in four different societies. METHODS: A total of 2263 children from grade 3 to grade 6, aged 9 to 12 years, in Brazil, Canada, P. R. China, and Southern Italy participated in the study. The participants completed a self-report measure of loneliness. Information about social behaviors and peer relationships was obtained from peer assessments. RESULTS: Multi-group analyses revealed that the overall patterns of relations among social behaviors, peer relationships and loneliness differed across the samples. Specifically, sociability was positively associated with peer relationships and made negative indirect contributions to loneliness through peer relationships in all four samples. Aggression made significant indirect contributions to the prediction of loneliness in Chinese children, but not in other samples. Shyness-sensitivity was associated with loneliness directly in Brazilian and Italian children and indirectly through peer relationships in Canadian children, but not associated with loneliness in Chinese children. CONCLUSIONS: The results suggest that the nature of children's loneliness may be affected by the broad socio-cultural context.