Combination chemotherapy is more effective than mono-chemotherapy and is widely used in clinical practice for enhanced cancer treatment. In this study, we investigated the potential synergistic effects of acetaminophen, a common component in many cold medicines, and romidepsin, a histone deacetylase (HDAC) inhibitor, in the A549 non-small cell lung cancer (NSCLC) cell line. The combination of acetaminophen and romidepsin also exerted significant cytotoxicity and apoptosis induced by activation of caspase-3 on tumor cells in vitro. Moreover, combination therapy significantly induced increased production of chemokines that stimulate migration of activated T-cells into tumor cells. This mechanism can lead to active T-cell mediated anti-tumor immunity in addition to the direct cytotoxic chemotherapeutic effect. Activated T-cells led to enhanced cytotoxicity in drug-treated A549 cells through interaction with tumor cells. These results suggested that the interaction between the two drugs is synergistic and significant. In conclusion, our data showed that the use of romidepsin and low concentrations acetaminophen could induce effective anti-tumor effects via enhanced tumor immune and direct cytotoxic chemotherapeutic responses. The combination of acetaminophen with romidepsin should be considered as a promising strategy for the treatment of lung cancer.
Alizadeh-Navaei, Reza;Rafiei, Alireza;Abedian-Kenari, Saeid;Asgarian-Omran, Hossein;Valadan, Reza;Hedayatizadeh-Omran, Akbar
Asian Pacific Journal of Cancer Prevention
/
v.17
no.1
/
pp.131-133
/
2016
Background: Combination chemotherapy regimes are common treatments for cancer. The aim of this study was to evaluation the effect of individual chemotherapeutic agents in comparison with a first line chemotherapy regime treatment in the AGS gastric cancer cell line by MTT assay. Materials and Methods: In this experimental study, AGS cells were grown in RPMI-1640 supplemented with 10% fetal calf serum and 100 IU/ml penicillin, and $10{\mu}g/ml$ streptomycinin, under a humidified condition at $37^{\circ}C$ with 5% CO2. All cells were washed with PBS and detached with trypsin, centrifuged and 8000 cells re-plated on to 96- well plates. LD50 doses of Epirubicin, Cisplatin and 5-fluorouracil were added to each well in mono or triple therapy. Anti-proliferative activities were determined by MTT assay after 24, 48 or 72 h. Results: Results of MTT assays showed that there were no significant differences among 3 drugs in monotherapy (p=0.088), but there was significant difference between combination therapy with epirubicin (P=0.031) and 5FU (p=0.013) on cell survival at 24 h. After 48 and 72 hours, cell viability showed significant differences between the 3 drugs (p=0.048 and P=0.000 for 48 and 72 h, respectively) and there was significant difference between combination therapy with epirubicin (P=0.035 and P=0.002 for 48 and 72 h, respectively). Conclusions: The results showed no significant differences between these chemotherapy drugs each given alone, but combination therapy with 3 drugs had significant effects on cell viability in comparison with epirubicin alone.
The prevalence of breast cancer is very high in Korea. Although the patients receive standard treatments, such as surgery, chemotherapy, or radiotherapy, they frequently experience recurrence or metastasis of their tumors. In addition, many patients with breast cancer also suffer from side effect symptoms induced by these standard treatments. Therefore, increasing numbers of patients now want to undergo treatment with traditional Korean medicine (TKM) in addition to conventional treatment. We present a case of 46-year-old female with recurred breast cancer. She first received two kinds of chemotherapy and then underwent surgery. She then also received 4 cycles of adjuvant chemotherapy. At a follow-up examination, she was informed of recurrent lesions on the right anterior chest wall. She started to receive TKM treatments together with a new chemotherapy. After about one month, the size of the recurred tumor in right chest wall had decreased. Her symptoms, such as shoulder pain, chest pain, and nausea induced by conventional therapy, were also improved. We suggest that a combination of TKM and chemotherapy is a promising treatment for breast cancer.
We have developed a fully automated high throughput drug screening (HTDS) system based on the microfluidic cell culture array to perform combinational chemotherapy. This system has 64 individually addressable cell culture chambers where the sequential combinatorial concentrations of two different drugs can be generated by two microfluidic diffusive mixers. Each diffusive mixer has two integrated micropumps connected to the media and the drug reservoirs respectively for generating the desired combination without the need for any extra equipment to perfuse the solution such as syringe pumps. The cell array is periodically exposed to the drug combination with the programmed LabVIEW system during a couple of days without extra handling after seeding the cells into the microfluidic device and also, this device does not require the continuous generation of solutions compared to the previous systems. Therefore, the total amount of drug being consumed per experiment is less than a few hundred micro liters in each reservoir. The utility of this system is demonstrated through investigating the viability of the prostate cancer PC3 cell line with the combinational treatments of curcumin and tumor necrosis factor-alpha related apoptosis inducing ligand (TRAIL). Our results suggest that the system can be used for screening and optimizing drug combination with a small amount of reagent for combinatorial chemotherapy against cancer cells.
We report the case of a patient with gastric adenocarcinoma with multiple liver metastases. This patient showed complete remission for more than 68 months after S-1/cisplatin combination chemotherapy and radical total gastrectomy. The patient, a 63-year-old man, presented with dyspepsia and difficulty in swallowing. Endoscopic findings showed a huge ulcero-infiltrative mass at the lesser curvature of the mid-body, extending to the distal esophagus. Biopsy revealed a poorly differentiated tubular adenocarcinoma. An abdominal computed tomography scan demonstrated multiple hepatic metastases. S-1/cisplatin combination chemotherapy was initiated, and following completion of six cycles of chemotherapy, the gastric masses and hepatic metastatic lesions had disappeared on abdominal computed tomography. Radical total gastrectomy and D2 lymphadenectomy combined with splenectomy were performed. The patient underwent three cycles of S-1/cisplatin combination chemotherapy followed by tegafur-uracil therapy for 1 year. He remained in complete remission for more than 68 months after surgery.
Objectives: Esthesioneuroblastoma is a rare malignant neoplasm that originates from the olfactory sensory cells. This tumor grows from the upper nasal cavity and ethmoid sinus and invades surrounding structures through the cribriform plate into intracranium or orbit in advanced stage. Even though there has been some controversies in determining standard treatment due to rarity of this tumor, the combination treatment of surgery and adjuvant radiation has been recommended for the locally advanced esthesioneuroblastomas. However, the recent clinical experiences of advanced cases showed that combination chemotherapy is highly effective to reduce tumor mass and improve clinical outcomes. Materials and Methods: The authors conducted a retrospective analysis of 6 esthesioneuroblastoma patients who were treated in our hospital from 1986. Results: The age of these patients was between 19 and 86 year-old. Among the 6 cases, 2 were diagnosed at stage B and 4 at stage C, according to Kadish classification. Anti-tumor treatments were performed in 5 patients. One patient refused active treatment and was lost to follow-up. Better survival outcome were observed in 3 patients who were treated with combination chemotherapy alone or combined modality treatment including chemotherapy. Conclusion: Based on our retrospective study, the combined treatment consisting of surgery, radiotherapy, and combination chemotherapy should be used to improve treatment results. And furthermore, innovative clinical approaches such as neoadjuvant chemotherapy, high-dose chemotherapy and autologous peripheral stem cell transplantation, which have been reported to have good therapeutic results, should be considered and applied actively.
Song, Wen-Guang;Wang, Yi-Feng;Wang, Rui-Lin;Qu, Yin-E;Zhang, Zhi;Li, Guo-Zhong;Xiao, Ying;Fang, Fang;Chen, Hong
Asian Pacific Journal of Cancer Prevention
/
v.14
no.2
/
pp.923-927
/
2013
Objective: This work aims to investigate the therapeutic regimen of brain metastatic cancers and the relationship between clinical features and prognosis. Methods: Clinical data of 184 patients with brain metastatic cancers were collected and analysed for the relationship between survival time and age, gender, primary diseases, quantity of brain metastatic foci, their position, extra cranial lesions, and therapeutic regimens. Results: The average age of onset was 59.1 years old. The median survival time (MST) was 15.0 months, and the patients with breast cancer as the primary disease had the longest survival time. Females had a longer survival time than males. Patients with meningeal metastasis had extremely short survival time. Those with less than 3 brain metastatic foci survived longer than patients with more than 3. The MST of patients receiving radiotherapy only and the patients receiving chemotherapy only were all 10.0 months while the MST of patients receiving combination therapy was 16.0 months. Multiple COX regression analysis demonstrated that gender, primary diseases, and quantity of brain metastatic foci were independent prognostic factors for brain metastatic cancers. Conclusions: Chemotherapy is as important as radiotherapy in the treatment of brain metastatic cancer. Combination therapy is the best treatment mode. Male gender, brain metastatic cancers originating in the gastrointestinal tract, more than 3 metastatic foci, and involvement of meninges indicate a worse prognosis.
Large bowel cancer shows the 4-5th frequency in cancers that occurs in Korea. The western medicine cures the Large bowel cancer by radiation, surgery and chemotherapy. While, Oriental medicine cures the Large bowel cancer by Herb-drugs, acupuncture, moxa and et al. With just one way of treating Large bowel cancer can't be effective remedy. Because each medicine has a strength and weakness, it is effective treatment when two medicine combines and supplement each other. We got the following result about a trend of oriental and western combination treatment for Large bowel cancer through studding records. 1. In Large bowel cancer, colon cancer is referred hematochezia(腸風下血), rectal cancer is refereed enterotoxin(腸毒), and anal cancer is accumulation of pathogens in yin(結陰). 2. The western medicine treats Large bowel cancer patient with surgery first. They need on assembly treatment such as chemical, radiation and immune treatment. In oriental medicine, they treats Large bowel cancer patients with differentiation of symptom and signs and treatment(辨證施治) for example, insufficiency of spleen and stomach(脾胃虛弱), collapse of the spleen-ql(脾氣下陷), stagnation of blood stasis and toxic agent(瘀毒內結), reinforcing both qi and blood(脾血下陷), stagnation of damp-phlegm(痰濕凝結) and cure for them by acupuncture and moxa too. 3. In combination with oriental and western medical treatment princple of Large bowel cancer by each stage is as follows. First stage is cured with radical surgery and herb-drugs without chemotherapy. The intermediate and terminal stage patients is used radiation before surgery, or after palliative surgery cour with chemotherapy, radiation and Herb-drugs. In terminal stage patients, unable for surgery, is used combination between chemotherapy, palliative radiation and Herb-drugs. 4. After radiation surgery, the terminal stage patients who have extensively lymph node metastasis or local contraindication is able to undergo combination of Herb-durgs and chemotherapy. 5. The cure-effect with oriental and western medicine combination treatment was better than that just with oriental or western medical treatment. 6. The merits of oriental and western medicine combination treatment lengthen one's life and diminish the bad effect of chemotherapy and complete radiation treatment, prevent from relapsing, maintain the balance in their environment of body and improve immunity.
Huang, Yu-Jing;He, Ai-Na;Sun, Yuan-Jue;Shen, Zan;Min, Da-Liu;Yao, Yang
Asian Pacific Journal of Cancer Prevention
/
v.16
no.6
/
pp.2391-2395
/
2015
Objective: The aim of this retrospective study was to evaluate the feasibility and efficacy of response to continuous-infusion ifosfamide and doxorubicin combination as second-line chemotherapy for patients with recurrent or refractory osteosarcoma. Materials and Methods: Eighteen recurrent or refractory osteosarcoma patients who were treated with continuous-infusion ifosfamide and doxorubicin combination between May 1999 and April 2011 were included in the analysis. Ifosfamide at $12g/m^2$ was administered by intravenous continuous infusion over 3 days, and doxorubicin $60mg/m^2$ was administered as an intravenous bolus injection on day 1. The combination therapy was repeated every 3 weeks. Treatment was continued until evidence of disease progression or unacceptable toxicity. Results: The patients (ages 7-53 years) received a total of 42 cycles of chemotherapy (median: 2 courses; range: 2-5 courses). The overall response rate was 0% and the disease control rate was 22.3%, with four patients having stable disease. The median time to progression and overall survival time were 2 months (range: 2-5 months) and 9 months (range: 3-29 months), respectively. Major severe toxicities were leucopenia 7 (38.9%), nausea and vomiting 3 (16.7%) and alopecia 9 (50%). There were no treatment-related deaths. Conclusions: In our experience, continuous-infusion ifosfamide and doxorubicin combination therapy at this dosage and schedule was found to be well tolerated and moderate effective, which could be considered as salvage therapy for patients with recurrent or refractory osteosarcoma. Further assessment is necessary to confirm the safety and efficacy of this treatment.
In the present case, the effect and toxicity of carboplatin and cyclophosphamide chemotherapy combined with surgery of mammary tumors in a dog were examined. An 8-year old spayed female Beagle presented with a mammary tumor. Physical examination, radiography, ultrasonography, computed tomography (CT), and laboratory examination were performed. Metastasis of the mammary tumor was confirmed by CT scan. Chemotherapy using a combination of carboplatin and cyclophosphamide was initiated following surgery. The first cycle of chemotherapy was planned to last for 6 weeks; it was planned that carboplatin would be intravenously administered for the first week (1 day) and cyclophosphamide would be intravenously administered for the next 3 weeks (22 days). Between the end of cycle 1 and the beginning of cycle 2, based on CT, it was confirmed that the number and size of tumors were unchanged and the tumors had not spread to other organs. However, at the end of cycle 2 and the beginning of cycle 3, CT revealed an increase in the number and size of mass in the lung. Chemotherapy was associated with adverse effects such as lethargy, anorexia, leukopenia, and hair loss. In conclusion, this case showed that a combination of carboplatin and cyclophosphamide suppressed the development of new neoplasms as well as metastasis for a certain period of time but did not improve the survival time. Although more cases are required, this chemotherapeutic procedure remains challenging.
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