• Asian Pacific Journal of Cancer Prevention
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• v.15 no.6
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• pp.2541-2546
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• 2014

Background: Primary hepatic neuroendocrine carcinoma (PHNEC) is rarer than extrahepatic gastrointestinal neuroendocrine carcinoma (NEC). It is difficult to make a correct diagnosis and poses a challenge for management. Materials and Methods: Ten PHNEC patients were admitted to our hospital from June 2006 to June 2011. Laboratory tests and imaging scans were performed for diagnosis and exclusion of extrahepatic NEC. All patients were AFP - and CA199-. Seven patients had solid tumors with cystic changes on ultrasonography, CT and/or MRI. For the initial treatment, four patients received combined-therapy and six monotherapy. Considering overall treatment, six patients received combined-therapy and four patients monotherapy. Staging criteria of primary hepatocellular carcinoma (PHC, AJCC 7th edition) were used to differentiate the stage of all patients: 3 patients were stage I, 2 stageII, 4 patients stageIII and 1 stageIV. All patients were followed up and clinical data were gathered. Results: The median follow-up duration was 38.5 months. The 1-year, 2-year, 3-year and 6-year disease-free survival was 80.0%, 46.2% and 46.2% and 0% respectively. The overall survival rates were 100%, 67.1%, 67.1% and 33.6% respectively. Patients in early-stages (I/II) had similar disease-free and overall survival as those in advanced-stages (III/IV). Patients with monotherapy had significant shorter disease-free and overall survival than the patients with combination-therapy. Conclusions: PHNEC has a unique specificity during its occurrence and development. The staging criteria of PHC might not be suitable for the PHENT. More convenient and effective features need to be found in imaging and laboratory detection. Surgical resection, TACE, chemotherapy and radiofrequency ablation should be performed in combination and actively for patients with PHNEC or recurrence to get the best effectiveness; they might extend the disease-free and overall survival.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.11
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• pp.5031-5035
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• 2016

Docetaxel, recognized as a stabilizing microtubule agent, is frequently administrated as a first line treatment for prostate cancers. Due to high side effects of monotherapy, however, combinations with novel adjuvants have emerged as an alternative strategy in cancer therapy protocols. Here, we investigated the combined effects of stattic and docetaxel on the DU145 prostate cancer cell line. Cytotoxicity was evaluated by MTT assay. To understand molecular mechanisms of stattic action, apoptotic related genes including Bcl-2, Mcl-1, Survivin and Bax were evaluated by real-time RT-PCR. Alteration in the expression of pro-apoptotic Bax and anti-apoptotic Bcl-2 genes and Bax/Bcl-2 ratio were investigated via the $2^{{\Delta}{\Delta}CT}$ method. The $IC_{50}$ values for docetaxel and stattic were $3.7{\pm}0.9nM$ and $4.6{\pm}0.8{\mu}M$, respectively. Evaluation of key gene expression levels revealed a noticeable decrease in antiapoptotic Bcl-2 and Mcl-1 along with an increase in pro-apoptotic Bax mRNA levels (p<0.05). Our results suggest that combination of a STAT3 inhibitor with doctaxel can be considered as a potent strategy for induction of apoptosis via increasing Bax mRNA expression.

• Parasites, Hosts and Diseases
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• v.40 no.1
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• pp.1-7
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• 2002

The purpose of treatment for uncomplicated malaria is to produce a radical cute using the combination of: artesunate (4 mg/kg/day) plus mefloquine (8 mg/kg/day) for 3 days; a fixed dose of artemether and lumefantrine (20/120 mg tablet) named $Coartem^{\circledR}$ (4 tablets twice a day for three days for adults weighing more than 35 kg); quinine 10 mg/kg 8-hourly plus tetracycline 250 mg 6-hourly for 7 days (or doxycycline 200 mg as an alternative to tetracycline once a day for 7 days) in patients aged 8 years and over; $Malarone^{\circledR}$ (in adult 4 tablets daily for 3 days). In treating severe malaria, early diagnosis and treatment with a potent antimalarial drug is recommended to save the patient's life. The antimalarial drugs of choice are: intravenous quinine or a parenteral form of an artemisinin derivative (artesunate i.v./i.m. for 2.4 mg/kg followed by 1.2 mg/kg injection at 12 and 24 hr and then daily for 5 days; artemether i.m. 3.2 mg/kg injection followed by 1.6 mg/kg at 12 and 24 hrs and then dialy for 5 days; arteether i. m. ($Artemotil^{\circledR}$) with the same dose of artemether or artesunate suppository (5 mg/kg) given rectally 12 hourly for 3 days. Oral arlemisinin derivatives (artesunate, artemether, and dihydroartemisinin with 4 mg/kg/day) could replace parenteral forms when patients can tolerate oral medication. Oral mefloquine (25 mg/kg divided into two doses 8 hrs apart) should be given at the end of the artemisinin treatment course to reduce recrudescence.

• Asian Pacific Journal of Cancer Prevention
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• v.13 no.7
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• pp.3471-3476
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• 2012

Background and Objective: Histone deacetylase (HDAC) inhibitors represent a promising class of potential anticancer agents for treatment of human malignancies. In this study, we investigated the effect of trichostatin A (TSA), one such HDAC inhibitor, in combination with docetaxel (TXT), a cytotoxic chemotherapy agent or erlotinib, a novel molecular target therapy drug, on lung cancer A549 cells. Methods: A549 cells were treated with TXT, erlotinib alone or in combination with TSA, respectively. Cell viability, apoptosis, and cell cycle distribution were evaluated using MTT (3- (4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay, Hochst33258 staining and flow cytometry. Moreover, immunofluorescent staining and Western blot analysis were employed to examine alterations of ${\alpha}$-tubulin, heat shock protein 90 (hsp90), epidermal growth factor receptor (EGFR), and caspase-3 in response to the different exogenous stimuli. Results: Compared with single-agent treatment, co-treatment of A549 cells with TSA/TXT or TSA/erlotinib synergistically inhibited cell proliferation, induced apoptosis, and caused cell cycle delay at the $G_2/M$ transition. Treatment with TSA/TXT or TSA/erlotinib led to a significant increase of cleaved caspase-3 expression, also resulting in elevated acetylation of ${\alpha}$-tubulin or hsp90 and decreased expression of EGFR, which was negatively associated with the level of acetylated hsp90. Conclusions: Synergistic anti-tumor effects are observed between TXT or erlotinib and TSA on lung cancer cells. Such combinations may provide a more effective strategy for treating human lung cancer.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.sup3
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• pp.287-291
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• 2016

Cervical cancer is one of the most common gynecological cancers in Iranian women. This study was initiated to assess whether the combination of paclitaxel and cisplatin with radiation might feasible for these patients. The aim was to assess tumor response and toxicity of weekly cisplatin and paclitaxel along with radiotherapy in the treatment of cervical cancer. Women with primary untreated squamous cell carcinoma of the cervix with FIGO stages IB2 to IIIB were treated with weekly injections of cisplatin 30 mg/m2 and paclitaxel 35 mg/m2 for 5-6 weeks along with radiotherapy. A total of 25 patients were enrolled in this study who completed the intended treatment. Disease was assessed prior to treatment by pelvic examination and contrast enhanced MRI of the abdomen and pelvis. Response was assessed 1 month after completion of treatment by physical examination and 3 months after also by MRI.Toxicity was assessed and was graded using RTOG grading. There was a complete response rate of 84% after 3 months. The major toxicity was grade 1 and 2 anemia (92%). The mean duration of treatment was 58 days. In conclusion, combination chemotherapy with cisplatin and paclitaxel along with radiotherapy in patients with locally advanced squamous cell carcinoma of cervixwas well tolerated, in contrast to other studies, but it seems that there was no increase in tumor response and progression free survival with this treatment regimen.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.17 no.3
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• pp.289-295
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• 1995

Malignant fibrous histiocytoma rarely occurs in the jaws. Although the histogenesis of this tumor remains controversal, it is best regarded as a primitive and pleomorphic nature reflected by collagen production and occasional phagocytosis. It is common for metastatic foci to appear in lung and regional lymph node. There are variable treatments such as radiotherapy, surgical excision or combination therapy of surgical excision, chemotherapy and radiotherapy. With the review of literatures, the authors report the clinical study of two cases of malignant fibrous histiocytoma of the jaw.

• Journal of Ginseng Research
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• v.45 no.5
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• pp.591-598
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• 2021

Background: Hematopoiesis is the production of blood cells from hematopoietic stem cells (HSCs) that reside in the bone marrow. Cyclophosphamide (CTX) is a chemotherapy drug that suppresses the immune system. Korean Red Ginseng (KRG) and Colla corii asini (CCA) have been traditionally used for boosting the immune system. Methods: HSCs in the bone marrow, and immune cell subtype in splenocytes, PBMCs, and thymocytes were investigated. Serum levels of hematopoietic-related markers were analyzed using ELISA. Protein expression in spleen tissue was analyzed using western blot analysis. Hematoxylin & eosin staining in the femurs of mice were also conducted. Results: The combination of KRG and CCA with a ratio of 3:2 increased HSCs, CD3 and CD8⁺ T cells in the circulation, and CD3 T cells in the spleen. A ratio of 2:3 (KRG:CCA) increased the thymic regulatory T cells and recovered the CD3 T cells in the spleen and circulation while recovering proteins in the JAK-STAT pathway in the spleen. Overall, blood cell population and differentiating factors vital for cell differentiation were also significantly recovered by all combinations especially in ratios of 3:2 and 2:3. Conclusion: A ratio of 3:2 (KRG:CCA) is the most ideal combination as it recovered the HSC population in the bone marrow of mice.

• Korean Journal of Veterinary Research
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• v.63 no.3
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• pp.30.1-30.8
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• 2023

Metformin is a treatment used widely for non-insulin-dependent diabetes mellitus with few side effects and acts by inhibiting hepatic gluconeogenesis and glucose absorption from the gastrointestinal tract. Lymphoma is one of the most common hematological malignancies in dogs. Chemotherapy is used mainly on lymphoma, but further research on developing anticancer drugs for lymphoma is needed because of its severe side effects. This study examined the anticancer effects of metformin alone and in combination with 2-deoxy-D-glucose (2-DG), a glucose analog, on EL4 cells (mouse T cell lymphoma). Metformin reduced the metabolic activity of EL4 cells and showed an additive effect when combined with 2-DG. In addition, cell death was confirmed using a trypan blue exclusion test, Hochest 33342/propidium iodide (PI) staining, and Annexin V/PI staining. An analysis of the cell cycle and mitochondria membrane potential (MMP) to investigate the mechanism of action showed that metformin stopped the G2/M phase of EL4 cells, and metformin + 2-DG decreased MMP. Metformin exhibited anticancer effects as a G2/M phase arrest mechanism in EL4 cells and showed additive effects when combined with 2-DG via MMP reduction. Unlike cytotoxic chemotherapeutic anticancer drugs, metformin and 2-DG are related to cellular glucose metabolism and have little toxicity. Therefore, metformin and 2-DG can be an alternative to reduce the toxicity caused by chemotherapeutic anticancer drugs. Nevertheless, research is needed to verify the in vivo efficacy of metformin and 2-DG before they can be used in lymphoma treatments.

• Tuberculosis and Respiratory Diseases
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• v.75 no.1
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• pp.9-17
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• 2013

Background: In cancer cells, autophagy is generally induced as a pro-survival mechanism in response to treatment-associated genotoxic and metabolic stress. Thus, concurrent autophagy inhibition can be expected to have a synergistic effect with chemotherapy on cancer cell death. Monensin, a polyether antibiotic, is known as an autophagy inhibitor, which interferes with the fusion of autophagosome and lysosome. There have been a few reports of its effect in combination with anticancer drugs. We performed this study to investigate whether erlotinib, an epidermal growth factor receptor inhibitor, or rapamycin, an mammalian target of rapamycin (mTOR) inhibitor, is effective in combination therapy with monensin in non-small cell lung cancer cells. Methods: NCI-H1299 cells were treated with rapamycin or erlotinib, with or without monensin pretreatment, and then subjected to growth inhibition assay, apoptosis analysis by flow cytometry, and cell cycle analysis on the basis of the DNA contents histogram. Finally, a Western blot analysis was done to examine the changes of proteins related to apoptosis and cell cycle control. Results: Monensin synergistically increases growth inhibition and apoptosis induced by rapamycin or erlotinib. The number of cells in the sub-$G_1$ phase increases noticeably after the combination treatment. Increase of proapoptotic proteins, including bax, cleaved caspase 3, and cleaved poly(ADP-ribose) polymerase, and decrease of anti-apoptotic proteins, bcl-2 and bcl-xL, are augmented by the combination treatment with monensin. The promoters of cell cycle progression, notch3 and skp2, decrease and p21, a cyclin-dependent kinase inhibitor, accumulates within the cell during this process. Conclusion: Our findings suggest that concurrent autophagy inhibition could have a role in lung cancer treatment.

• The Journal of Internal Korean Medicine
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• v.28 no.3
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• pp.531-543
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• 2007

Backgrounds : Gastric cancer is one of the most frequent causes of cancer-related deaths worldwide. Gastric cancer patients frequently exhibit distant metastasis at the time of diagnosis and at present, there is no standard regimen after operation or chemotherapy to prevent metastasis and recurrences. Aims : The objective of the study was to compare the overall survival and disease free survival in patients treated with wheel balance therapy (WBT) with patients treated with WBT alone or the combination of WBT and conventional therapy and see if there were any significant improvements in survival between the two groups. Setting & Design : East-West Cancer Center at Daejeon University: retrospective study. Materials & Methods : We retrospectively analyzed 62 patients with stage III (40 patients) and stage IV (22 patients) gastric cancer who have received operation or chemotherapy 2 months prior to beginning WBT. The patients followed the WBT protocol which includes herbal medicine such as PSM capsules, OnePlus syrup, or HAD capsules which prevent metastasis and recurrences. Overall survival and disease free survival were analyzed and the patients were treated for 89.55 weeks and 49.27 weeks (median value) for stages III and IV, respectively. Statistical analysis used : Overall survival and disease free survival were estimated using the Kaplan-Meier method and the WBT and combination treatment arms were compared using the log rank test. Results : For stage III, the 3 year overall survival was 78.5% and disease free survival was 78.3%. Metastasis and recurrence occurred in 13 of 40 patients (32.5%). For stage IV, the 2 year overall survival was 18.2% and disease free survival was also 18.2%. Metastasis and recurrence occurred in 19 of 22 patients (86.4%). No significant difference was found statistically between the WBT alone and combination treatment arms though the combination regimen showed superiority (overall survival p=0.5093, disease free survival p=0.5175). Conclusions : WBT yielded satisfactory results in prolonging survival and preventing metastasis and recurrence in gastric cancer patients. The major treatment unit of WBT is composed of herbal medications (HAD, PSM capsules, OnePlus syrup) and a randomized, prospective study should be carried out using only this treatment unit in the future.