• Title/Summary/Keyword: drug combinations

Search Result 97, Processing Time 0.024 seconds

Breakthroughs in the Systemic Treatment of HER2-Positive Advanced/Metastatic Gastric Cancer: From Singlet Chemotherapy to Triple Combination

  • Sun Young Rha;Hyun Cheol Chung
    • Journal of Gastric Cancer
    • /
    • v.23 no.1
    • /
    • pp.224-249
    • /
    • 2023
  • Gastric cancer is heterogeneous in morphology, biology, genomics, and treatment response. Alterations in human epidermal growth factor receptor 2 (HER2) overexpression, microsatellite instability (MSI) status, programmed death-ligand 1 (PD-L1) levels, and fibroblast growth factor receptor 2 (FGFR2) can be used as biomarkers. Since the combination of fluoropyrimidine/platinum plus trastuzumab that was investigated in the ToGA trial was approved as a standard of care in HER2-positive patients in 2010, no other agents showed efficacy in the first- (HELOISE, LOGiC, JACOB trials) and second- (TyTAN, GATSBY, T-ACT trials) line treatments. Despite the success in treating breast cancer, various anti-HER2 agents, including a monoclonal antibody (pertuzumab), an antibody-drug conjugate (ADC; trastuzumab emtansine [T-DM1]), and a small molecule (lapatinib) failed to translate into clinical benefits until the KEYNOTE-811 (first-line) and DESTINY-Gastri01 (≥second-line) trials were conducted. The incorporation of HER2-directed treatment with immune checkpoint inhibitors in the form of a monoclonal antibody or ADC is now approved as a standard treatment. Despite the promising results of new agents (engineered monoclonal antibodies, bi-specific antibodies, fusion proteins, and small molecules) in the early phase of development, the management of HER2-positive gastric cancer requires further optimization to achieve precision medicine with a chemotherapeutic backbone. Treatment resistance is a complex process that can be overcome using a combination of chemotherapy, targeted agents, and immune checkpoint inhibitors, including novel agents. HER2 status must be reassessed in patients undergoing anti-HER2 treatment with disease progression after the first-line treatment. As a general guideline, patients who need systemic treatment should receive chemotherapy plus targeted agents, anti-angiogenic agents, immune checkpoint inhibitors, or their combinations.

Evaluation of Microbial Analysis and Application of Reduction Technology in a Dairy Factory (목장형 유가공장의 미생물 분석 및 저감기술 적용 평가)

  • Jong-Hui Kim;Eun-Seon Lee;Bu-Min Kim;Jun-Sang Ham;Mi-Hwa Oh
    • Journal of Dairy Science and Biotechnology
    • /
    • v.41 no.4
    • /
    • pp.203-210
    • /
    • 2023
  • Bacterial contamination negatively affects the quality, functionality, and safety of dairy products. Adherent populations of bacteria, referred to as biofilms, grow on the surfaces of dairy processing equipment and are the primary cause of dairy contamination. In addition, microorganisms present in the farm environment and dairy factory can contaminate the Clear-In-Place (CIP) line through raw milk transport pipes; therefore, exhaustive management is required. In dairy manufacturing facilities, biofilm formation is controlled using CIP systems that primarily require sodium hydroxide and nitric acid. However, the leakage or incomplete removal of these potently active compounds can be harmful to humans. In the present study, we compared the eradication of Escherichia coli and other bacteria using commercially available combinations of sodium hypochlorite (NaClO) and citric acid, which are recognized by the Korean Ministry of Food and Drug Safety (MFDS) as food disinfectants. When considered in the CIP system of the field manufacturing process, E. coli was not detected (compared to detection before treatment), and other bacteria were detected at 0-32 culture-forming units (CFU)/cm2. The residual amount of chlorine ions after CIP treatment was similar to that in tap water, and there was no significant difference in the overall components of the fermented dairy products. Therefore, the NaClO/citric acid CIP system can be safely applied in dairy manufacturing processes.

Antimicrobial drug susceptibility and treatment efficacy in mice against Escherichia coli and Salmonella spp isolated from feces of diarrheal animals (가축의 설사변에서 분리한 대장균과 살모넬라균의 항균물질 감수성과 마우스에서의 치료효과)

  • Kim, Jong-man;Jean, Nam-seop;Kim, Jong-wan;Jean, Young-hwa;Lee, Hee-soo;Kweon, Chang-hee;Woo, Sung-ryong;Lee, Hae-chon;Park, Jong-myung;Kim, Jae-hak;Rhee, Jae-chin
    • Korean Journal of Veterinary Research
    • /
    • v.37 no.2
    • /
    • pp.389-403
    • /
    • 1997
  • Survey on MIC of antimicrobial drugs and its treatment efficacy in mice were conducted for the strains of Escherichia coli and Salmonella spp isolated from feces of young domestic animals with diarrhea in 1996. A total of 338 strains of E coli and 61 strains of Salmonella spp were examined for the susceptibility to 20 antibiotics and 7 synthetic antimicrobial drugs. The results indicated that the majority of strains were susceptible to amikacin(93.5%), cefoperazone/sulbactam(93.5%), cefotaxim(93.3%), cefomandole(92.8%), cefoperazone(91.6%) and ciprofloxacin(85.1%), in order. Although gentamicin, ciprofloxacin and norfloxacin showed the relatively low MIC distributions, erythromycin, doxycycline, sulfamethoxazole and oxytetracycline revealed the high MIC distributions to most of isolates. The $MIC_{90}$ of antimicrobials for E coli were > $62.5{\mu}g/ml$ in gentamicin, $2.0{\mu}g/ml$ in ciprofloxacin, $1.0{\mu}g/ml$ in norfloxacin, > $500{\mu}g/ml$ in erythromycin, $125{\mu}g/ml$ in doxycycline, > $1000{\mu}g/ml$ in sulfamethoxazole and > $250{\mu}/ml$ in oxytetracycline. In general, the MIC of E coli isolates was higher than that of Salmonella spp isolates. Although variation in synergism or additivity of antibiotic combinations were demonstrated, ampicillin-gentamicin was the most efficacious combination both against E coli and Salmonella spp with the fluctuation of 7.7-77.5%. In the experiment of treatment efficacy in mice, the highest survival ratio(83.3%) after challenge with pathogenic E coli and Salmonella typhimurium was detected in the group treated with gentamicin.

  • PDF

Effect of Herbal Extracts Mixtures on Antioxidant System in Chronic Enthanol-treated Rats

  • Kim, Mok-Kyung;Won, Eun-Kyung;Choung, Se-Young
    • Biomolecules & Therapeutics
    • /
    • v.14 no.4
    • /
    • pp.226-234
    • /
    • 2006
  • Disturbance of antioxidant system is very common in chronic alcoholics and herbal or natural products with antioxidant activity have been used for its treatment. This study was to investigate the effect of Vitis vinifera extract(V), Schisandra chinensis extract(S), Taraxacum officinale extract(T), Gardenia jasminoides extract(G), Angelica acutiloba extract(A) and Paeonia japonica extract(P), and their combinations on the antioxidant and ethanol oxidation system. Male Sprague-Dawley rats were subjected to Lieber-DeCarli ethanol liquid diet(ED) and were then given different herbal extract mixtures for 6 weeks including VST(V 100+S 150+T 150mg/kg/day), VSG(V 100+S 150+G 150mg/kg/day), VTG(V 100+T 150+G 150mg/kg/day), and VAP(V 100+A 150+P 150mg/kg/day). When the activity of alcohol dehydrogenase(ADH) and acetaldehyde dehydrogenase(ALDH) were compared between ED only group and herbal extracts treatment group, the differences were statistically significant. Phase I and II(glutathione-S-transferase, phenol sulfatransferase) enzyme activities were found to be significantly higher in the VAT treatment group compared to the ED group. Herbal extracts not only repressed the ethanol-induced elevation of malondialdehyde level, but also protected against ethanol-induced decrease in glutathione content, glutathione reductase, glutathione peroxidase, catalase and superoxide dismutase activities. The administration of the herbal extracts was found to be effective in eliminating lipid-peroxides induced by long-term consumption of alcohol by activating various enzyme systems and physiological active compound formation system. After a chronic consumption of alcohol, Angelica Radix protected the liver via activating the ethanol-metabolism enzyme system, and Paeoniae Radix via activating the ethanol-metabolism enzyme and the phase I, II-metabolism enzyme system. Taraxaci Herba was also effective in liver protection via activating the ethanol-metabolism enzyme system and the phase I, II-metabolism enzyme system, Gardeniae Fructus via activating the phase II-metabolism enzyme system and the anti-oxidation system enzyme, and Schisandra Fructus and a grapestone via activating the anti-oxidation system. Our data suggest that these herbal extracts may be useful as a health functional food or new drug candidate for fatty liver and hepatotoxicity induced by chronic alcohol consumption.

Factors Attributing to the Formation of N-Nitrosamines in Instant Food (즉석 식품에서 니트로사민이 검출되는 요인 분석)

  • Suh, Bokyung;Kwon, Hoonjeong
    • Journal of Food Hygiene and Safety
    • /
    • v.32 no.2
    • /
    • pp.114-122
    • /
    • 2017
  • N-nitrosamines can be produced in the process of heating, processing, storage and packaging. Migration specifications for N-nitrosamines exist only for rubber baby bottle nipples, which are regulated by the Ministry of Food and Drug Safety (MFDS). There is no regulation for other food contact substances (FCS) and studies on N-nitrosamines migration from FCS are rather limited. A pilot study showed an increase in N-nitrosamines contents when cooking instant noodles. Thus, the migration from the packaging was suspected and it was necessary to monitor the migration of N-nitrosamines from food packaging materials and to examine the change in N-nitrosamines contents when cooking instant foods. Three N-nitrosamines, NDMA (N-nitrosodimethtlamine), NDEA (N-nitrosodiethylamine), NDBA (N-nitrosodibutylamine), were analyzed in migration test solutions from plastics such as polyethylene, polypropylene and polystyrene, papers and aluminium containers. In all test solutions, N-nitrosamines were detected less than method quantitation limits (MQLs). Food samples were also investigated to ensure that there is no effect from food contact substances when cooking instant foods. In retort sauces such as curry, black soybean sauce and tomato sauce, NDMA concentration was ranged from 0.54 to $3.81{\mu}g/kg$, but there were no significant differences between unheated and heated samples. However, the NDMA contents were significantly increased in most of the instant noodle samples tested when cooked (p < 0.05). No effects from the food contact substances or cooking water was observed. Only when the seasoning powder and noodles were cooked together was NDMA detected. Individual components (noodle, seasoning powder or dried vegetable) or other combinations such as noodles and dried vegetables did not generate N-nitrosamines. Therefore, it is speculated that NDMA may be formed from the precursors in noodles and seasoning powders when they are solubilized in a medium of water.

Clinical Study of Topotecan as Second-Line Treatment in Small Cell Lung Cancer (소세포폐암의 2차요법으로서의 Topotecan의 치료효과)

  • Kim, Hak-Ryul;Yang, Sei-Hoon;Jeong, Eun-Taik
    • Tuberculosis and Respiratory Diseases
    • /
    • v.52 no.3
    • /
    • pp.230-240
    • /
    • 2002
  • Background : The majority of chemotherapy-treated small cell lung cancers(SCLC) patients eventually recur. Although many patients are in excellent physical condition at the time of recurrence, few drugs or drug combinations are capable of effecting a tumor regression in this setting. Topotecan, a topoisomerase I inhibitor, is one of the more widely studied single afents in SCLC. The aim of this study was to determine the response rate, survival and toxicity of topotecan as a second line traeatment SCLC. Materials and Methods : 19 patients with measurable SCLC, progressive during the first line chemotherapy (9 cases) or recurrent after the first line chemotherpy(10 cases), were enrolled in this study. Topotecan was administered as a 30-minute daily infusion at a dose of 1.5mg/$m^2$ for 5 consecutive days, every 3 weeks. Results : The overall response rate was 26.3%(5/19, CR 2, PR 3, SD 3, PD 11). The median survival was 24 weeks. The response rate and survival were poor in the nonresponders during first chemotherapy, those who were refractory to the first chemotherapy(recurrent within 3 months after completion of first chemotherapy) and extensive disease, but the results were not statistically significant. The toxicities were mainly hematologic and anemia grade III 1/90, leukopenia grade III 6/90 IV 4/90, thrombocytopenia grade III 1/90 IV 1/90, vomiting grade III 1/90 of cycles were occurred. There was no treatment-related deaths due to severe myelosuppression. Conclusion : Topotecan can be an active second line chemotherapeutic agent for treating SCLC.

Review of Anti-Leukemia Effects from Medicinal Plants (항 백혈병작용에 관련된 천연물의 자료조사)

  • Pae Hyun Ock;Lim Chang Kyung;Jang Seon Il;Han Dong Min;An Won Gun;Yoon Yoo Sik;Chon Byung Hun;Kim Won Sin;Yun Young Gab
    • Journal of Physiology & Pathology in Korean Medicine
    • /
    • v.17 no.3
    • /
    • pp.605-610
    • /
    • 2003
  • According to the Leukemia and Lymphoma Society, leukemia is a malignant disease (cancer) that originates in a cell in the marrow. It is characterized by the uncontrolled growth of developing marrow cells. There are two major classifications of leukemia: myelogenous or lymphocytic, which can each be acute or chronic. The terms myelogenous or lymphocytic denote the cell type involved. Thus, four major types of leukemia are: acute or chronic myelogenous leukemia and acute or chronic lymphocytic leukemia. Leukemia, lymphoma and myeloma are considered to be related cancers because they involve the uncontrolled growth of cells with similar functions and origins. The diseases result from an acquired (not inherited) genetic injury to the DNA of a single cell, which becomes abnormal (malignant) and multiplies continuously. In the United States, about 2,000 children and 27,000 adults are diagnosed each year with leukemia. Treatment for cancer may include one or more of the following: chemotherapy, radiation therapy, biological therapy, surgery and bone marrow transplantation. The most effective treatment for leukemia is chemotherapy, which may involve one or a combination of anticancer drugs that destroy cancer cells. Specific types of leukemia are sometimes treated with radiation therapy or biological therapy. Common side effects of most chemotherapy drugs include hair loss, nausea and vomiting, decreased blood counts and infections. Each type of leukemia is sensitive to different combinations of chemotherapy. Medications and length of treatment vary from person to person. Treatment time is usually from one to two years. During this time, your care is managed on an outpatient basis at M. D. Anderson Cancer Center or through your local doctor. Once your protocol is determined, you will receive more specific information about the drug(s) that Will be used to treat your leukemia. There are many factors that will determine the course of treatment, including age, general health, the specific type of leukemia, and also whether there has been previous treatment. there is considerable interest among basic and clinical researchers in novel drugs with activity against leukemia. the vast history of experience of traditional oriental medicine with medicinal plants may facilitate the identification of novel anti leukemic compounds. In the present investigation, we studied 31 kinds of anti leukemic medicinal plants, which its pharmacological action was already reported through many experimental articles and oriental medical book: 『pharmacological action and application of anticancer traditional chinese medicine』 In summary: Used leukemia cellline are HL60, HL-60, Jurkat, Molt-4 of human, and P388, L-1210, L615, L-210, EL-4 of mouse. 31 kinds of anti leukemic medicinal plants are Panax ginseng C.A Mey; Polygonum cuspidatum Sieb. et Zucc; Daphne genkwa Sieb. et Zucc; Aloe ferox Mill; Phorboc diester; Tripterygium wilfordii Hook .f.; Lycoris radiata (L Her)Herb; Atractylodes macrocephala Koidz; Lilium brownii F.E. Brown Var; Paeonia suffruticosa Andr.; Angelica sinensis (Oliv.) Diels; Asparagus cochinensis (Lour. )Merr; Isatis tinctoria L.; Leonurus heterophyllus Sweet; Phytolacca acinosa Roxb.; Trichosanthes kirilowii Maxim; Dioscorea opposita Thumb; Schisandra chinensis (Rurcz. )Baill.; Auium Sativum L; Isatis tinctoria, L; Ligustisum Chvanxiong Hort; Glycyrrhiza uralensis Fisch; Euphorbia Kansui Liou; Polygala tenuifolia Willd; Evodia rutaecarpa (Juss.) Benth; Chelidonium majus L; Rumax madaeo Mak; Sophora Subprostmousea Chunet T.ehen; Strychnos mux-vomical; Acanthopanax senticosus (Rupr.et Maxim.)Harms; Rubia cordifolia L. Anti leukemic compounds, which were isolated from medicinal plants are ginsenoside Ro, ginsenoside Rh2, Emodin, Yuanhuacine, Aleemodin, phorbocdiester, Triptolide, Homolycorine, Atractylol, Colchicnamile, Paeonol, Aspargus polysaccharide A.B.C.D, Indirubin, Leonunrine, Acinosohic acid, Trichosanthin, Ge 132, Schizandrin, allicin, Indirubin, cmdiumlactone chuanxiongol, 18A glycyrrhetic acid, Kansuiphorin A 13 oxyingenol Kansuiphorin B. These investigation suggest that it may be very useful for developing more effective anti leukemic new dregs from medicinal plants.