instruction:
In this task, you are given a passage which has a question and the context. You have to generate an answer to the question based on the information present in the context.
question:
Context: Hypoxia is associated with human non-small cell lung cancers (NSCLC), which are highly resistant to chemotherapy. The hypoxia inducible factor (HIF) as a transcription factor in response to hypoxia indicates that it could be a novel, tumor-specific target for anticancer therapy. We hypothesized that disruption of HIF pathway through lentiviral vector-mediated HIF-1alpha RNA interference (RNAi) could reverse the hypoxia-induced resistance to chemotherapy.', 'We transfected Human NSCLC cell lines, SPCA1 and A549 with HIF-1alpha specific RNAi lentiviral vectors as well as controls. HIF-1alpha silenced cells [SPCA1/HIF-1alpha(-) and A549/HIF-1alpha(-)] were screened by blasticidin. They were incubated in 19 or 0.5% O2 for 16 h followed by the assessment of chemosensitivity to cisplatin and doxorubicin with MTT and clonogenic assays. Quantitative RT-PCR and Western blot analysis were used to detect the expressions of HIF-1alpha mRNA and protein, respectively. Moreover, flow cytometry was used to monitor the expression of P-glycoprotein.', 'Exposure of SPCA1 and A549 cells to 0.5% O2 significantly increased resistance to cisplatin and doxorubicin, in contrast to cells incubated in normoxia. Transduction of SPCA1 with HIF-1alpha RNAi vector resulted in sequence specific silencing with 87.2 and 84.6% decreases of HIF-1alpha mRNA transcription and 97.3 and 94.8% of protein expressions in normoxia and hypoxia, respectively. Correspondingly, they are 89.2, 89.9% and 97.2, 88.4% decreases in A549 cells. Hypoxia-induced resistance to cisplatin and doxorubicin were reversed in SPCA1/HIF-1alpha(-) and A549/HIF-1alpha(-) cells. There was no significant P-glycoprotein increase induced by hypoxia in NSCLC cells.\Question: Is hypoxia-induced resistance to cisplatin and doxorubicin in non-small cell lung cancer inhibited by silencing of HIF-1alpha gene?
answer:
Our studies demonstrated that hypoxia-induced chemoresistance to cisplatin and doxorubicin in NSCLC cells is through the HIF pathway. MDR1 regulation may not be involved in hypoxia-induced chemoresistance. Combining delivery of HIF-1alpha RNAi lentiviral vector with cisplatin-related chemotherapy regimens may enable us to develop more effective strategy for NSCLC therapy.


question:
Context: To test whether oral L-81 treatment could improve the condition of mice with diabetes and to investigate how L-81 regulates microsomal triglyceride transfer protein (MTP) activity in the liver.', 'Genetically diabetic (db/db) mice were fed on chow supplemented with or without L-81 for 4 wk. The body weight, plasma glucose level, plasma lipid profile, and adipocyte volume of the db/db mice were assessed after treatment. Toxicity of L-81 was also evaluated. To understand the molecular mechanism, HepG2 cells were treated with L-81 and the effects on apolipoprotein B (apoB) secretion and mRNA level of the MTP gene were assessed.', 'Treatment of db/db mice with L-81 significantly reduced and nearly normalized their body weight, hyperphagia and polydipsia. L-81 also markedly decreased the fasting plasma glucose level, improved glucose tolerance, and attenuated the elevated levels of plasma cholesterol and triglyceride. At the effective dosage, little toxicity was observed. Treatment of HepG2 cells with L-81 not only inhibited apoB secretion, but also significantly decreased the mRNA level of the MTP gene. Similar to the action of insulin, L-81 exerted its effect on the MTP promoter.\Question: Does pluronic L-81 ameliorate diabetic symptoms in db/db mice through transcriptional regulation of microsomal triglyceride transfer protein?
answer:
L-81 represents a promising candidate in the development of a selective insulin-mimetic molecule and an anti-diabetic agent.


question:
Context: Locally advanced colorectal cancer often requires extended resection to radically remove all tumor. This is the only chance for cure in these patients, but a higher complication rate would be expected. To evaluate the overall benefit for the patient, this study assesses morbidity and mortality as well as long-term survival of patients who underwent extended resection for a T3-T4 carcinoma.', 'Two hundred twenty patients with locally advanced adenocarcinoma of the colorectum were included. One hundred fifty presented with a T3 and 70 with a T4 tumor. Eighty-three patients underwent extended resection. In 38 patients extended en bloc resection was performed because of inflammatory adherence mimicking infiltration. Thirty-three patients who underwent extended resections were over 70 years of age. There were no significant differences between the groups that underwent extended or nonextended resections in age, sex, stage, or grading.', 'pT4 lesions were significantly more frequent in the extended resection group than in the nonextended resection group. Mean survival was 44 months after extended resections and 45 months after nonextended resections. In the extended resection group there was no significant difference in mean survival between pT3 and pT4 stage patients within 46 and 38 months, respectively. In patients who underwent nonextended resections, however, there was a significant difference in mean survival within 48 months for pT3 and 28 for pT4 patients (P < 0.05). Postoperative morbidity and mortality were comparable between the extended resection group and the non-extended resection group. The presence of residual tumor influenced prognosis of patients significantly; R0 resections fared significantly better than patients who underwent R1 or R2 resections (55 and 51 to 14/12 and 23/8 months) (P < 0.01). Nodal stage and International Union Against Cancer stage were also significant determinants of prognosis. After extended resections mean survival morbidity and 30-day mortality in patients more than 70 years was similar to those less than 70 years.\Question: Are extended resections beneficial for patients with locally advanced colorectal cancer?
answer:

Because extended resections can achieve comparable results in locally more advanced colorectal cancer as nonextended resections in less advanced cancer, an aggressive surgical approach is warranted.