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Introduction: Hypersensitivity to chemotherapeutic and biological agents has increased in recent years due to their frequent use. Avoidance has been the first line of defense, leading to decreased treatment efficacy and increased adverse events. Objective: To characterize the sociodemographic and clinical aspects of patients with hypersensitivity reactions to chemotherapeutic agents who underwent desensitization and biological procedures in a Colombian city. Methods: This observational, descriptive, retrospective, multicenter study was conducted in patients with hypersensitivity reactions to chemotherapeutic and biological agents who underwent desensitization. Results: In the 14 included patients with a history of hypersensitivity reactions to chemotherapeutic and biological agents (57.1% women; median age 42.5 years), 45 desensitization procedures were performed. The most commonly prescribed drug was rituximab (57%). The skin was the most frequent reaction site (78.6%), and systemic corticosteroids were the most common treatment (78.6%). Breakthrough reactions occurred in 31.1% of the patients and only premedication with corticosteroids was associated with less severe reactions. All cases of desensitization were successful. Conclusions: Desensitization to chemotherapeutic and biological agents proved to be a useful and safe tool in a Colombian population.
Introdução: A hipersensibilidade aos agentes quimioterápicos e biológicos aumentou nos últimos anos devido ao seu uso frequente. Evitar tem sido a primeira linha de ação, levando à diminuição da eficácia do tratamento e ao aumento de eventos adversos. Objetivos: Caracterizar os aspectos sociodemográficos e clínicos de pacientes com reações de hipersensibilidade a agentes quimioterápicos submetidos a dessensibilização e procedimentos biológicos em uma cidade colombiana. Métodos: Foi realizado um estudo observacional, descritivo, retrospectivo e multicêntrico em pacientes com reações de hipersensibilidade a agentes quimioterápicos e biológicos submetidos à dessensibilização. Resultados: Foram incluídos 45 procedimentos de dessensibilização em 14 pacientes com histórico de reações de hipersensibilidade a agentes quimioterápicos e biológicos (57,1% mulheres, com mediana de idade de 42,5 anos). O medicamento mais relatado foi o rituximabe (57%). O envolvimento cutâneo foi o mais frequente (78,6%) e os corticosteroides sistêmicos foram o tratamento mais utilizado (78,6%). As reações ocorreram em 31,1% e apenas a pré-medicação com corticosteroides foi associada a uma menor gravidade destas. Todos os casos de dessensibilização foram bem-sucedidos. Conclusões: A dessensibilização a agentes quimioterápicos e biológicos provou ser uma ferramenta útil e segura em uma população colombiana.
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HumansABSTRACT
【Objective】 To investigate the effects of WM-3835, a histone acetyltransferase KAT7 (KAT7) inhibitor, on the proliferation and migration of bladder cancer cells and to explore the possible mechanism. 【Methods】 Human ureteral epithelial immortalized cell line SV-HUC-1, and bladder cancer cell lines UM-UC-3 and T24 were treated with different concentrations of WM-3835 (0, 10, 20, 30, 40 μmol/L). After 48 hours, the effects of WM-3835 on the proliferation, cell cycle distribution and migration of cells were detected with MTT assay, flow cytometry, scratch and Transwell assay, respectively. The expressions of cyclin D1 (cyclin D1), proliferating nuclear antigen (PCNA), matrix metalloproteinase 9 (MMP9) and neurocadherin (N-cadherin) were detected with Western blotting and real-time quantitative PCR. 【Results】 WM-3835 significantly inhibited the proli-feration of bladder cancer cells in a dose-dependent manner. After treatment with WM-3835, the cycle of UM-UC-3 and T24 cells were blocked in the G0/G1 phase, the proliferation was effectively inhibited, and the migration was significantly wea-kened. The expressions of cyclin-D1, PCNA, MMP9 and N-cadherin were down-regulated. 【Conclusion】 WM-3835 can inhibit the proliferation and migration of bladder cancer cells, and has the potential as a chemotherapeutic agent for bladder cancer.
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Objective To compare the therapeutic efficacy of preventive transcatheter arterial chemoembolization (TACE) with that of preventive transhepatic arterial infusion (TAI) for patients with primary hepatocellular carcinoma (HCC) after hepatectomy. Methods During the period from June 2011 to June 2012 at authors’ hospital, preventive transhepatic interventional therapy was employed in 79 HCC patients within three months after hepatectomy. The followed-up endpoint was in June 2013. The clinical data were retrospectively analyzed. The patients were divided into TACE group (n=41) and TAI group (n=38). No significant differences in age, sex, preoperative liver function, Child-Pugh scores, tumor size and AFP level existed between the two groups. During interventional procedure , catheterization of proper hepatic artery was performed first, which was followed by angiography in order to clarify that there were no newly-developed tumor vessels or tumor lesions in the residual liver, then the chemotherapeutic agents were infused through the catheter. The emulsion of iodized oil with chemotherapeutic agent was used in the patients of TACE group, while only chemotherapeutic agent was adopted in the patients of TAI group. By using Chi-square test the one-year recurrence rate was determined. Kaplan-Meier estimation method was used to calculate the disease-free survival time, and t test was adopted to estimate the mean hospitalization days. The results were compared between the two groups. Results Of the 79 patients, postoperative recurrence was confirmed in 11, and the overall one-year recurrence rate was 13.9%. The one-year recurrence rate of TACE group and TAI group was 12.20% and 15.79% respectively , and no significant difference in one- year recurrence rate existed between TACE group and TAI group (χ2= 0.213, P = 0.645). The average disease-free survival time of TACE group and TAI group was (21.60 ± 1.52) months and (17.38 ± 3.01) months respectively, the difference between the two groups was of statistical significance (P = 0.038). The mean hospitalization days of TACE group and TAI group were (6.30 ± 1.84) days and (5.89 ± 2.08) days respectively, and the difference between the two groups was not statistically significant (P = 0.522). Conclusion No significant difference in one-year recurrence rate exists between the patients receiving preventive TACE and the patients receiving preventive TAI after hepatectomy for HCC. Nevertheless , preventive TACE can probably improve the disease-free survival time after hepatectomy.
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Objective To investigate the anti-leukemia adriamycin (ADR) effect of membrane protein Splicing factor proline/glutamine-rich (SFPQ).Methods HL-60 and its adriamycin-resistant cells HL-60/ADR were cultured in vitro.Expression of SFPQ on HL-60 and HL-60/ADR cell membranes were examined by immunofluorescence.McAb 5D12 was used to block membrane SFPQ protein activity.ADR susceptibility and cell proliferation were analyzed by MTT assay.IC50 values of ADR in HL-60 and HL-60/ADR cell lines and up-regulations in cell proliferation induced by 5D12 were calculated.Intracellular accumulation of rhodamine in HL-60 and HL-60/ADR cells were measured using fluorescence-activated cell sorting.Results Expression of SFPQ on cell membrane was higher in HL-60 cells compared to the HL-60/ADR cell line.After membraneblocking with 5D12,ADR sensitivity was decreased in vitro compared with the untreated cells [the 48 h IC50 value,HL-60 cell line (0.19±0.03) μg/ml vs (0.95±0.13) μg/ml,HL-60/ADR cell line (14.41±2.42) μg/ml vs (21.33±4.26) μg/ml].Blocking of membrane SFPQ by 5D12 did not affect the intracellular accumulation of rhodamine in these cells,however,5D12 induced HL-60 and HL-60/ADR cell proliferation,following 1,3,5,8 and 12 μg/ml 5D12 treatment for 96 h were (9.12±2.02) ％,(16.63±0.92) ％,(19.04±0.25) ％,(24.17±0.53) ％,(34.04±3.20) ％ (HL-60),and (7.40±2.23) ％,(8.72±2.38) ％,(10.47±3.78) ％,(11.57±1.49) ％,(13.97±0.91) ％ (HL-60/ADR),respectively.Conclusion Nuclear protein-SFPQ contributes to HL-60′ ssensitivity to adriamycin by increasing its surface expression and promoting cell proliferation,but the protein has no significant effect on the intracellular accumulation of the drug.
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PURPOSE: Adjuvant chemotherapy is currently recommended for Stage IIIA colon cancers. This study aimed to elucidate the oncologic outcomes of Stage IIIA colon cancer according to the chemotherapeutic regimen based on a retrospective review. METHODS: From 1995 to 2008, Stage IIIA colon cancer patients were identified from a prospectively maintained database at a single institution. Exclusion criteria were as follows: rectal cancer, another malignancy other than colon cancer, no adjuvant chemotherapy and unknown chemotherapeutic regimen. One hundred thirty-one patients were enrolled in the study, and the clinicopathologic and the oncologic characteristics were analyzed. The number of males was 72, and the number of females was 59; the mean age was 59.5 years (range, 25 to 76 years), and the median follow-up period was 33 months (range, 2 to 127 months). RESULTS: Of the 131 patients, fluorouracil/leucovorin (FL)/capecitabine chemotherapy was performed in 109 patients, and FOLFOX chemotherapy was performed in 22 patients. When the patients who received FL/capecitabine chemotherapy and the patients who received FOLFOX chemotherapy were compared, there was no significant difference in the clinicopathologic factors between the two groups. The 5-year overall survival and the 5-year disease-free survival were 97.2% and 94.5% in the FL/capecitabine patient group and 95.5% and 90.9% in the FOLFOX patient group, respectively, and no statistically significant differences were noted between the two groups. CONCLUSION: Stage IIIA colon cancer showed good oncologic outcomes, and the chemotherapeutic regimen did not seem to affect the oncologic outcome.
Subject(s)
Female , Humans , Male , Chemotherapy, Adjuvant , Colon , Colonic Neoplasms , Disease-Free Survival , Follow-Up Studies , Prognosis , Prospective Studies , Rectal Neoplasms , Retrospective StudiesABSTRACT
Drug resistance is major obstacles in the successful treatment of malignant solid tumors. Multiple mechanisms involeve in development of cancer drug resistance. Recent research suggests dysregulation of microRNAs is associated with cancer drug resistance. The profiles of microRNAs in drug resistance cancer cells or tissues are different with sensitivity cells or tissues in various solid tumors. Restoring microRNAs could improve chemosensitivity of cancer cells. MicroRNAs expression profiles may provide a critical link for understanding mechanisms involved in chemoresistance. We can also find a specific marker for screening chemosensitivity patients through identification of the microRNAs patterns of drug resistance cells or tissues.
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Cancer is the first leading cause of death in Korea. Systemic chemotherapy is currently the standard treatment for a wide variety of cancers; however, in the majority of cases, cure is not achieved, and the attendant side effects of the treatment are considerable. The effectiveness of chemotherapy in cancers depends on the adequate delivery of the chemotherapeutic agent to cancer cells. The achievement of uniform drug delivery of chemotherapeutic agents throughout tumors is limited by the anomalous vascularization and blood vessel permeability. Ultrasound has an ever-increasing role in the delivery of therapeutic agents including chemotherapeutic agents, proteins, and genetic materials. Ultrasound technology allows for the use of focused ultrasound energy for therapeutic purposes by delivering high-intensity focused ultrasound for applications such as tissue ablation, and enhanced drug delivery. We reviewed recent work in the emerging field of ultrasound-based therapeutics, with particular emphasis on the delivery of drugs to tumor tissue.
Subject(s)
Humans , Antineoplastic Agents/administration & dosage , Drug Delivery Systems , Drug Evaluation, Preclinical , Lung Neoplasms/drug therapy , Neoplasms/drug therapy , UltrasonicsABSTRACT
PURPOSE: Infertility due to ovarian failure that is caused by antineoplastic chemotherapeutic agents is one of the primary problems of female cancer atients who are in their reproductive years. It has become important to preserve the reproductive potential of female cancer patients. This study was conducted to determine whether autotransplantation of frozen ovaries can restore reproductive potential. METHODS: This study included 30 female mice that had normal reproductive potential. The mice were divided into 4 groups: the positive control, the negative control, the comparison group, and the experimental group. The positive control group received right total oophorectomy, and the negative control group received bilateral total oophorectomy. Greater than or equal to 90% of the left ovary was removed in the mice of the comparison group, and then cyclophosphamide was administered. In the experimental group, the right ovary taken out by right total oophorectomy, and this was crypreserved using the vitrification method. And then cyclophosphamide was administered. The cryopreserved ovary was autotransplanted to the left gonadal fat pad after greater than or equal to 90% of the left ovary was removed. The reproductive performance in each group was analyzed according to the pregnancy rate after mating. RESULTS: In the positive control group, all five mice became pregnant, and the number of fetuses was 4 to 5 (mean=4.60+/-0.55). In the comparison group, the pregnancy rate was 50%, and the mean number of fetuses was 1.40+/-0.55. In the experimental group, 7 of 10 (70%) mice became pregnant, and the mean number of fetuses was 4.71+/-2.56. There was no significant difference in the number of fetuses between the positive control and the experimental group (p=0.093), but there was a significant difference in the number of fetuses between the comparison group and the experimental group (p=0.019). CONCLUSION: The results of this study suggest that autotransplantation of frozen ovaries using the vitrification method may restore the impaired ovarian function induced by antineoplastic chemotherapeutic agents.
Subject(s)
Animals , Female , Humans , Mice , Adipose Tissue , Cyclophosphamide , Fetus , Gonads , Infertility , Ovariectomy , Ovary , Pregnancy Rate , VitrificationABSTRACT
PUPOSE: We reported our preliminary result in 2001. At that time, the follow-up period was too short to evaluate the survival benefit of adjuvant chemotherapy in gastric cancer without serosal invasion. Therefore, we followed those patients for 66 months to determine the long-term effects of adjuvant chemotherapy. MATERIALS AND METHODS: We analyzed the recurrence pattern, the survival rate, and the disease-specific survival of 135 patients by reviewing their medical records and calling the patients or their relatives. All enrolled patients were included in the intention-to-treat analysis of efficacy. RESULTS: The follow-up rate was 89.6% (121/135), and the median follow-up duration was 66 months. Among the 135 patients, 4 relapsed in group 1 (5-FU cisplatin), 7 in group 2 (mitomycin C oral 5-FU), and 6 in group 3 (oral 5-FU only). The overall survival rate was 89% in group 1, 84% in group 2, and 82% in group 3. There were no differences in the overall survival rates and the disease-specific survival rates among the three groups. CONCLUSION: Oral chemotherapeutic agents have an acceptable effect for adjuvant chemotherapy compared with intravenous agent. However, a large-scale, prospective, randomized study, including a control group, is needed for an exact evaluation.
Subject(s)
Humans , Chemotherapy, Adjuvant , Fluorouracil , Follow-Up Studies , Medical Records , Prospective Studies , Recurrence , Stomach Neoplasms , Survival RateABSTRACT
OBJECTIVE: Because of the limited penetration into the central nervous system after systemic administration of numerous therapeutic compounds, intratumoral chemotherapy for brain tumors has also been used. However, the efficacy of intratumoral drug administration is restricted by the poor diffusion of drug through tumor and brain interstitium. In order to enhance the diffusion of chemotherapeutic agent and increase the cytotoxicity with minimal dose, the authors report the results of convection-enhanced delivery(CED) of chemotherapeutic agent to the malignant brain tumor as a method of enhancing cerebral drug delivery. METHODS: Authors used "CADD-Micro(R) ambulatory infusion pump" from Deltec, which can be programmed for continuous infusion. Intratumoral injection of chemotherapeutic drug using the pump was applied to eight patients with glioma and one patient with lymphoma. Surgery was done and tumor was removed as much as possible. The tip of catheter was placed in the center of tumor cavity. Adriamycin (0.16~0.32mg) was put in the reservoir which was connected to the proximal catheter and fixed in the pump device. Twenty-four hours after surgery, Adriamycin was infused. RESULTS: There was no adverse reaction of CED technique. Compared with current delivery techniques, the improvement of survival rate has been observed(5 patients: alive, 3 patients: dead, 1 patient: lost(alive to 5 mo.)). CONCLUSION: CED can be useful method for distributing therapeutic molecules in the interstitial space of tumor and can be utilized for chemotherapeutic agents, immunotoxins, and gene etc..
Subject(s)
Humans , Brain , Brain Neoplasms , Catheters , Central Nervous System , Diffusion , Doxorubicin , Drug Therapy , Glioma , Immunotoxins , Lymphoma , Survival RateABSTRACT
Subject(s)
Animals , Mice , Apoptosis , Bone Marrow , Capillaries , Carcinoma, Squamous Cell , Cell Death , Cell Line , Cicatrix , Europe , Fibrosis , Heterografts , Mass Screening , Mice, Nude , Mouth Neoplasms , Necrosis , Viscum albumABSTRACT
Objective To observe the inhibitory effect of 5 chemotherapeutic agents including vincristine,adriamycin,pingyangmycin,cisplatin,cyclophosphamide on the KBV200 cell line and to study the reverse effect on the multidrug resistance of Matrine.Methods MTT assay was used to investigate the inhibition ability of 5 drugs on the cell line and the reverse effect on the multidrug resistance of Matrine.Results Vincristine,pingyangmycin,cyclophosphamide had less inhibitory effects than adriamycin,cisplatin on the KBV200 cell line.Matrine had the ability to reverse the multidrug resistance of the cell line to vincristine,adriamycin.Conclusion KBV200 cell line is multidrug-resistant to vincristine,pingyangmycin,cyclophosphamide.Matrine can enhance the sensitivity of KBV200 to the vincristine,adriamycin.
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We report a case of atypical eruption due to chemotherapeutic agent in a 60-year-old man who presented with asymptomatic, erythematous, 0.5cm in diameter, confluent, and elevated papules and plaques confined to the face. The patient was previously diagnosed with small cell carcinoma of the lung with liver metastasis. Two months after the diagnosis, a first course of chemotherapy including etoposide was started. Five days after starting the chemotherapy, the patient developed a facial eruption. Histopathologic examination demonstrated increased epidermal mitotic figures, cells in metaphase arrest, basal cell layer hyperpigmentation, prominent dyskeratosis, and squamous atypia. The most distinctive histologic feature was the presence of starburst cells, which are markedly enlarged pale staining keratinocytes containing small basophilic fragments of nuclear debris haphazardly scattered throughout the cytoplasm in a starburst pattern.
Subject(s)
Humans , Middle Aged , Basophils , Carcinoma, Small Cell , Cytoplasm , Diagnosis , Drug Therapy , Etoposide , Hyperpigmentation , Keratinocytes , Liver , Lung , Metaphase , Neoplasm MetastasisABSTRACT
PURPOSE: Resistance to anticancer chemotherapeutic drug remains a major obstacle in cancer chemotherapy. Multidrug-resistance(MDR) gene overexpression and detoxification by glutathione are believed to be involved in adriamycin and cisplatin resistance. We investigated change of p-glycoprotein(MDR gene product) expression, cellular glutathione content and glutathione peroxidase and glutathione transferase activities by hyperthermia to elucidate the synergistic mechanism of hyperthermia with chemotherapeutic agent. MATERIALS AND METHODS: Human renal cell carcinoma cell lines, Caki-1 and A-498 were used. Control temperature was 37OC and hyperthermia of 43OC was applied in 2 and 4 hours durations. P-glycoprotein expression was measured by flowcytometric examination using monoclonal antibody to p-glycoprotein. Glutathione content and activities of glutathione peroxidase and transferase were measured by biochemical methods. RESULTS: Glutathione content and activities of glutathione peroxidase and transferase were not changed by hyperthermia. However, p-glycoprotein expression was reduced by hyperthermia of 43OC. CONCLUSIONS: These results suggest that reduced p-glycoprotein expression by hyperthermia causes increased intracellular accumulation of chemotherapeutic agent by decreasing drug efflux mechanism and plays an important role in synergistic effect with adriamycin and cisplatin cytotoxicities.