多形性胶质母细胞瘤术后联合化疗病人的护理

多形性胶质母细胞瘤在神经上皮性肿瘤中占22．3％，占颅内肿瘤的10．2％，仅次于星型细胞瘤。由于其浸润性生长，与周围正常脑组织无明显界限，手术难以全部切除，术后联合化疗是综合治疗的手段之一。1999年4月-2004年11月，联合应用卡莫司汀（BCNU）、5-氟尿嘧啶（5-FU）、替尼泊苷（VM-26）用于45例多形性胶质母细胞瘤术后病人的化疗。现就其临床护理报告如下。     

多形性胶质母细胞瘤术后联合化疗病人的护理

多形性胶质母细胞瘤在神经上皮性肿瘤中占22.3%,占颅内肿瘤的10.2%,仅次于星型细胞瘤。由于其浸润性生长,与周围正常脑组织无明显界限,手术难以全部切除,术后联合化疗是综合治疗的手段之一。1999年4月—2004年11月,联合应用卡莫司汀(BCNU)、5-氟尿嘧啶(5-FU)、替尼泊苷(VM-26)用于45例多形性胶质母细胞瘤术后病人的化疗。现就其临床护理报告如下。1临床资料1.1一般资料本组45例,男26例,女19例,年龄13岁～77岁,平均年龄44.9岁。均经组织学证实为多形性胶质母细胞瘤。肿瘤部位:额叶29例,顶叶9例,枕叶4例,基底核2例,小脑1例。1.2病例选择①…     

A combination of benznidazole and ketoconazole enhances efficacy of chemotherapy of experimental Chagas' disease

Despite the large number of patients infected with Trypanosoma cruzi, there are no commercial drugs available with high efficacy for use in the clinical treatment of Chagas' disease (American trypanosomiasis). As the prospects of the introduction of new compounds by the pharmaceutical industry are poor, alternative strategies are being designed to identify candidates among drugs already available on the market that could be used in combination to provide a synergic effect and improve the efficacy of chemotherapy. In this paper we investigated a possible synergic effect of drugs in mice inoculated with isolates of T. cruzi susceptible (CL), moderately resistant (Y) and naturally resistant (Colombiana) to benznidazole and nifurtimox. Our data demonstrated that the combination of benznidazole with ketoconazole induced a synergic effect in mice infected with the CL and Y isolate of T. cruzi. No differences were observed, however, in animals infected with the Colombiana isolate, suggesting that the synergic effect of benznidazole and ketoconazole is influenced by the isolate of parasite and that this could be important in further studies searching for useful combinations of drugs. Moreover, we observed that early treatment with ketoconazole could increase the cure rate in animals infected with the Y isolate. No positive effect, in relation to cure rate, was observed with the combination of benznidazole and ofloxacin. Our results re-emphasize the importance of identifying those compounds already on the market with synergic effects able to enhance the cure of T. cruzi infection.     

术后辅助不同放化疗方案治疗多形性胶质母细胞瘤患者的疗效比较

目的研究术后不同辅助治疗手段对多形性胶质母细胞瘤患者生存期的影响,不同因素对预后的影响。方法对手术治疗的41例病理诊断为胶质母细胞瘤的术后患者进行随访和回顾性研究。所有患者都接受至少近全切的手术。其中7例行单纯手术治疗,10例行术后单纯放疗,12例行术后尼莫司汀化疗＋放疗,12例行术后替莫唑胺化疗＋放疗。利用生存曲线Kaplan-Meier法比较胶质母细胞瘤患者术后经过4种不同治疗方案治疗的生存期是否存在显著差异。结果41例胶质母细胞瘤患者术后经过不同的放化疗,总体平均生存期和中位生存期都为11个月（2—27个月）。单纯手术治疗组中位生存期6个月,中位无进展生存期4个月,6个月生存率57．1％;术后单纯放疗组中位生存期10个月,中位无进展生存期5个月,6个月生存率90．0％,12个月生存率50．0％;术后尼莫司汀＋放疗组中位生存期13个月,中位无进展生存期5个月,6个月生存率100％,12个月生存率66．7％;术后替莫唑胺＋放疗组中位生存期13个月,中位无进展生存期7个月,6个月生存率66．7％,12个月生存率58．3％。经过Kaplan-Meier生存分析,单纯手术胶质母细胞瘤患者生存期显著低于术后放化疗组患者的生存期（P〈0．05）;术后单放疗组患者生存期显著低于术后尼莫司汀＋放疗组（P=0．039）和替莫唑胺＋放疗组（P=0．049）,术后替莫唑胺＋放疗组与尼莫司汀＋放疗组生存期比较无统计学差异,但两化疗组较单纯手术组和术后单纯放疗组患者生存期显著延长（P〈0．05）。术后替莫唑胺化疗组中位无进展生存期较单纯手术组显著延长（P〈0．05）,其余各组之间差异无统计学意义。结论术后早期辅助放化疗可以延长胶质母细胞瘤患者中位生存期。     

Subreum efficacy and tolerance in patients with early rheumatic arthritis]

AIM: To evaluate effectiveness and tolerance of subreum in early rheumatoid arthritis (RA). MATERIAL AND METHODS: 44 patients with early rheumatoid arthritis. Subreum was given as a single drug and in combination with other basic drugs. Tolerance was evaluated in all the examinees, the effect--in 13 patients who finished the 6-month treatment by the articular syndrome, by ACR, DAS and HAQ criteria. RESULTS: By DAS, a good response was achieved in 2 patients (15%), a satisfactory one--in 3 (23%) patients. By ACR criteria, a 20% and 50% improvement was obtained in 3 (23%) and 4 (31%) patients. Side effects were absent in 41 (93%) patients. CONCLUSION: Subreum proved effective and well tolerable in early RA.     

Gene therapy for tolerance and vice versa: a case for hemophilia

Hemophilia is a bleeding disorder that affects approximately 1 in 4000 males across populations worldwide. First-line therapy for the treatment of hemophilia is the intravenous administration of protein therapeutics to replace the deficient coagulation factor. However, in a significant number of patients, the immune system recognizes the therapeutic protein as 'dangerous' and mounts a humoral response that rejects the treatment and significantly increases the morbidity associated with this disease. Recent advances have been made in gene therapy in the field of hemophilia. Gene therapy provides the possibility of a cure for this disease; however, managing immunological tolerance to therapy is a challenge for this treatment modality. This review describes an approach in which gene therapy is used to deliver a tolerogenic construct to B-cells that can induce tolerance to protein therapy or to replacement gene therapy. Several other novel techniques to modulate immunity in patients with hemophilia, such as non-specific agents, mAbs and protein modifications, are at various stages of translation to the clinic and are also highlighted. The successful modulation of the immune system to accept treatment will significantly improve the quality of life for patients with hemophilia.     

The efficacy of cytoplasmatic therapy in elderly patients

It has been studied whether cytoplasmatic therapy with macromolecular substances can favourably influence symptoms of the progressive aging process in old patients. For this purpose a randomized double-blind study was carried out in a geriatric clinic. A marked and statistically significant improvement was observed in the patients after four weeks real treatment as compared with the placebo group, using as criteria the ECG, the frequency of cerebral symptoms and the result of psychological tests. Concomitant chemical and haematological laboratory controls did not indicate a difference between the two treatment groups.     

Comparative efficacy and tolerance of atenolol and midodrine in patients with vasovagal syncopes

AIM: To compare efficacy and tolerance of atenolol and midodrine in patients with vasovagal syncopes (VVS). MATERIAL AND METHODS: The trial included 35 patients with recurrent VVS confirmed at long passive head-up tilt table test (HTTT) or maximal load bicycle exercise test (MET). These tests were also used for assessing efficacy of atenolol and midodrine in cases when syncopes occur in repeated tests. If recurrent induction of VVS was absent, efficacy of the drugs was assessed by long-term (up to 12 months) clinical observation. Long-term administration of atenolol and midodrine was continued in patients with effect by HTTT and/or MET. Eighteen patients were randomized to take atenolol in a daily dose up to 50 mg, seventeen--to take midodrine in a daily dose up to 15 mg. RESULTS: Efficacy of atenolol by HTTT and MET was 8%, midodrine--57% (p = 0.01). All the patients benefited from the drugs in their long-term regimen. Long-term administration of atenolol induced remission of VVS in 82% cases, midodrine--in 89% (insignificant). Overall efficacy of atenolol was 44%, of midodrine--70% (insignificant). In 5 of 6 patients resistant to atenolol and midodrine monotherapy, combined use of the drugs was effective. Treatment with atenolol, midodrine and their combination prevented VVS in 89% patients. Both short- and long-term courses of atenolol and midodrine were safe in terms of side effects. CONCLUSION: Atenolol and midodrine as well as their combination were highly effective and well tolerated in the treatment of VVS patients.     

Immune tolerance improves the efficacy of enzyme replacement therapy in canine mucopolysaccharidosis I

Mucopolysaccharidoses (MPSs) are lysosomal storage diseases caused by a deficit in the enzymes needed for glycosaminoglycan (GAG) degradation. Enzyme replacement therapy with recombinant human alpha-L-iduronidase successfully reduces lysosomal storage in canines and humans with iduronidase-deficient MPS I, but therapy usually also induces antibodies specific for the recombinant enzyme that could reduce its efficacy. To understand the potential impact of alpha-L-iduronidase-specific antibodies, we studied whether inducing antigen-specific immune tolerance to iduronidase could improve the effectiveness of recombinant iduronidase treatment in canines. A total of 24 canines with MPS I were either tolerized to iduronidase or left nontolerant. All canines received i.v. recombinant iduronidase at the FDA-approved human dose or a higher dose for 9-44 weeks. Nontolerized canines developed iduronidase-specific antibodies that proportionally reduced in vitro iduronidase uptake. Immune-tolerized canines achieved increased tissue enzyme levels at either dose in most nonreticular tissues and a greater reduction in tissue GAG levels, lysosomal pathology, and urinary GAG excretion. Tolerized MPS I dogs treated with the higher dose received some further benefit in the reduction of GAGs in tissues, urine, and the heart valve. Therefore, immune tolerance to iduronidase improved the efficacy of enzyme replacement therapy with recombinant iduronidase in canine MPS I and could potentially improve outcomes in patients with MPS I and other lysosomal storage diseases.     

Interleukin-4 enhances the in vitro precursor cell recruitment for tumor-specific T lymphocytes in patients with glioblastoma

Previously the authors showed that interleukin-4 (IL-4), used in combination with IL-2, increases the reduced proliferation rate of T cells of glioblastoma-bearing patients after in vitro autologous immunization. In this report, they sought to determine whether this effect is caused by a direct mitogenic effect of IL-4, or rather by an indirect effect through an increased expression of the IL-2 receptor subunits or an enhanced recruitment of responsive cells. Flow cytometric analysis confirmed that the IL-2 receptor subunits are less expressed on circulating T cells from patients with glioblastoma than on those from healthy donors. Because no significant modification of the expression of the p55 and p75 subunits of the IL-2 receptor is observed in cultures treated with both IL-2 and IL-4, the reported enhanced proliferation rate cannot be attributed to an increased level of IL-2 receptor expression. Limiting dilution assays, using autologous target cell immunization, show that treatment with both cytokines (IL-2 plus IL-4) significantly increases the number of recruitable precursor cells without affecting their proliferation rate. These results indicate that IL-4 facilitates an immune response against the autologous tumor cells in glioblastoma-bearing patients by increasing the recruitable precursor T-cell frequency.     

Comparison of patient-controlled and nurse-controlled antiemetic therapy in patients receiving chemotherapy

The purpose of this quasi-experimental pilot study was to compare the effect of patient-controlled (PCAE) and nurse administered (NCAE) antiemetic therapy for controlling chemotherapy-induced nausea and vomiting in patients receiving moderate emetogenic chemotherapy. Twenty subjects were randomly assigned to either the PCAE group who received IV antiemetic medication via a patient-controlled pump or the NCAE group who received antiemetic medication via nurse administered minibags. Nausea, vomiting, sedation, and drug consumption were measured. There was no difference in nausea scores between the two groups. Subjects in the PCAE group consumed significantly less medication than subjects in the NCAE group.     

CD47 blockade enhances the efficacy of intratumoral STING-targeting therapy by activating phagocytes

Activation of STING signaling plays an important role in anti-tumor immunity, and we previously reported the anti-tumor effects of STING through accumulation of M1-like macrophages in tumor tissue treated with a STING agonist. However, myeloid cells express SIRPα, an inhibitory receptor for phagocytosis, and its receptor, CD47, is overexpressed in various cancer types. Based on our findings that breast cancer patients with highly expressed CD47 have poor survival, we evaluated the therapeutic efficacy and underlying mechanisms of combination therapy with the STING ligand cGAMP and an antagonistic anti-CD47 mAb using E0771 mouse breast cancer cells. Anti-CD47 mAb monotherapy did not suppress tumor growth in our setting, whereas cGAMP and anti-CD47 mAb combination therapy inhibited tumor growth. The combination therapy enhanced phagocytosis of tumor cells and induced systemic anti-tumor immune responses, which rely on STING and type I IFN signaling. Taken together, our findings indicate that coadministration of cGAMP and an antagonistic anti-CD47 mAb may be promising for effective cancer immunotherapy.     

Gene therapy and angiogenesis in patients with coronary artery disease

Not all patients with severe coronary artery disease can be treated satisfactorily with current recommended medications and revascularization techniques. Various vascular growth factors have the potential to induce angiogenesis in ischemic tissue. Clinical trials have only evaluated the effect of VEGF and FGF in patients with coronary artery disease. The initial small and unblinded studies with either recombinant growth factor proteins or genes encoding growth factors were encouraging, demonstrating both clinical improvement and evidence of angiogenesis. However, subsequent larger double-blind placebo-controlled trials could not confirm the initial high efficacy of either the growth factor protein or the gene therapy approaches observed in earlier small trials. The clinical studies so far have all been without any gene-related serious adverse events. Future trials will focus on whether an improvement in clinical results can be obtained with a cocktail of growth factors or by a combination of gene and stem cell therapy in patients with severe coronary artery disease, which cannot be treated effectively with current treatment strategies.     

Anti-integrin monoclonal antibody CNTO 95 enhances the therapeutic efficacy of fractionated radiation therapy in vivo

Selective targeting of up-regulated integrins on tumor cells is a novel antiangiogenesis strategy for treating solid tumors. CNTO 95 is a fully human anti-alpha(v) integrin monoclonal antibody and has shown antitumor activity when used as a single agent in preclinical studies. We previously showed that radiation combined with an integrin alpha(v)beta(3) antagonist cRGD peptide increased the therapeutic efficacy of radiation in preclinical tumor models. We hypothesized that the combination of radiation and CNTO 95 would synergistically enhance the efficacy of radiation therapy. The in vitro studies showed that CNTO 95 radiosensitized and induced apoptosis in M21 cells in vitronectin-coated dishes. In mice bearing established human cancer xenograft tumors, CNTO 95 alone had only a moderate effect on tumor growth. The combined therapy of CNTO 95 and fractionated radiation significantly inhibited tumor growth and produced the longer tumor growth delay time in multiple tumor models. Maintenance dosing of CNTO 95 following irradiation contributed to efficacy and was important for continued inhibition of tumor regrowth. Immunohistochemistry studies showed that the combined use of CNTO 95 and radiation reduced the alpha(v) integrin and vascular endothelial growth factor receptor expression and the microvessel density and increased apoptosis in tumor cells and the tumor microenvironment. CNTO 95 alone and in combination with radiation did not produce any obvious signs of systemic toxicity. These results show that CNTO 95 can potentiate the efficacy of fractionated radiation therapy in a variety of human cancer xenograft tumor types in nude mice. These findings are very promising and may have high translational relevance for the treatment of patients with solid tumors.     

Gef gene therapy enhances the therapeutic efficacy of cytotoxics in colon cancer cells

The potential use of gene therapy to improve the response of patients with advanced cancer is being intensively analyzed. We evaluated the cytotoxic impact of the gef gene, a suicide gene, which has a demonstrated antiproliferative activity in tumor cells, in colon carcinoma cells in order to improve the antitumour effect of chemotherapeutic drugs used as first line treatment in the management of advanced colon cancer. We found that the gef gene induced a marked decrease in cell viability (50% in 24 h) in T-84 cells through cell death by apoptosis. Interestingly, when gef gene expression was combined with drugs of choice in the clinical treatment of colon cancer (5-fluorouracil, oxaliplatin and irinotecan), a strong synergistic effect was observed with approximately a 15–20% enhancement of the antiproliferative effect. Our data demonstrate, for the first time, that gef gene expression induces significant growth arrest in colon cancer cells and that it is able to enhance the effect of some cytotoxic drugs compared with a single therapeutic approach. These results indicate the potential therapeutic value of the gef gene in colon cancer combination therapy.