Purpose: We determined the therapeutic effect of an epidermal growth factor receptor (EGFR)-specific monoclonal antibody (mAb), cetuximab (Erbitux) on the growth of oral squamous cell carcinoma (OSCC) xenografted in athymic nude mice. Experimental Design: We induced subcutaneous tumors by inoculating human tumor cell suspension into the right flank of nude mice. Nude mice with subcutaneous tumors were randomized to receive cetuximab alone, paclitaxel alone, cetuximab plus paclitaxel, or a placebo (control). Antitumor mechanisms of cetuximab were determined by immunohistochemical and apoptosis assays. Results: Cetuximab, paclitaxel, and cetuximab/paclitaxel combined therapy resulted in 50%, 52%, 67% in vivo inhibition of tumor proliferation, respectively. Tumors of mice treated with cetuximab plus paclitaxel demonstrated decreased PCNA-positive tumor cells and increased apoptotic tumor cells, which slowed growth of the murine tumors. Conclusion: These data show that EGFR can be a molecular target for the treatment of OSCC. And combination therapy with cetuximab and paclitaxel warrants further clinical study.
Successful anticancer strategies require a differential response between tumor and normal tissue (i.e., a therapeutic ratio). In fact, improving the effectiveness of a cancer therapeutic is of no clinical value in the absence of a significant increase in the differential response between tumor and normal tissue. Although radiation dose escalation with the use of intensity modulated radiation therapy has permitted the maximum tolerable dose for most locally advanced cancers, improvements in tumor control without damaging normal adjacent tissues are needed. As a means of increasing the therapeutic ratio, several new approaches are under development. Drugs targeting signal transduction pathways in cancer progression and more recently, immunotherapeutics targeting specific immune cell subsets have entered the clinic with promising early results. Radiobiological research is underway to address pressing questions as to the dose per fraction, irradiated tumor volume and time sequence of the drug administration. To exploit these exciting novel strategies, a better understanding is needed of the cellular and molecular pathways responsible for both cancer and normal tissue and organ response, including the role of radiation-induced accelerated senescence. This review will highlight the current understanding of promising biologically targeted therapies to enhance the radiation therapeutic ratio.
Alberto Martinez-Martinez;Jade Garcia-Espinosa;Antonio Jesus Lainez Ramos-Bossini;Fernando Ruiz Santiago
Korean Journal of Radiology
/
v.22
no.6
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pp.944-950
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2021
Objective: To demonstrate the feasibility of percutaneous microwave ablation in desmoid fibromatosis with respect to tumor volume control and improvement in the quality of life. Materials and Methods: Twelve microwave ablations were performed in 9 patients with a histological diagnosis of desmoid fibromatosis between January 2010 and January 2019. The study population included 6 female and 3 male, with an age range of 21-76 years (mean = 46.6 years; standard deviation [SD] = 19.3 years). The mean major axis of the tumors was 10.9 cm (SD = 5.2 cm) and mean lesion volume was 212.7 cm3 (SD = 213 cm3). Their anatomical distribution was as follows: 3 lesions in the thigh, 2 in the gluteus, 2 in the leg and 2 in the periscapular region. We evaluated the reduction in tumor volume and improvement in the quality of life based on the Eastern Cooperative Oncology Group (ECOG) scale. Results: An average tumor volume reduction of 70.4% (SD = 24.9) was achieved, while the quality of life (ECOG scale) improved in 88.9% of patients. Conclusion: Percutaneous microwave ablation may potentially be a safe, effective, and promising technique for controlling tumor volume and improving the quality of life in patients with desmoid fibromatosis.
Hyangpaeyangyeongtang, which was first prescribed in the book of Euijonggumgam (醫宗金鑑), has been widely applied to the treatment of scrofula and carbuncle in the neck and tumor as well in the oriental medicine. The Fritillariae roylei bulbus was also used as an anti-tumor medicine. In order to investigate the effect of Hyangpaeyangyeongtang and Fritillariae roylei bulbus extracts on the immune responses to the epithelioma induced by 3-methylcholanthrene and prostaglandin-$F_2{\alpha}$ in mice, the change of epithelioma size was observed and delayed type hypersensitivity, hemagglutinin titer, hemolysin titer, rosette forming cells, natural killer cell activity, lymphocyte transformation, productivity of interleukin-2 and phagocytic activity were also measured. The results were as follows; 1. The epithelioma size was decreased with statistical significance in the Hyangpaeyangyeongtang group at the 14th day, as compared with the control group. 2. Delayed type hypersensitivity was not shown any decrease in the Hyangpaeyangyeongtang group and the Fritillariae roylei bulbus group, as compared with the control group. 3. Hemagglutinin titer was increased with statistical significance in the Hyangpaeyangyeongtang group, but not in the Fritillariae roylei bulbus group as compared with the control group. 4. Hemolysin titer was increased with statistical significance in the Hyangpaeyangyeongtang group, but not in the Fritillariae roylei bulbus group as compared with the control group. 5. Rosette forming cells were not increased in the Hyangpaeyangyeong tang group, but increased with statistical significance in the Fritillariae roylei bulbus group as compared with the control group. 6. Natural killer cell activity at the ratio 100:1 of effector cells to target cells was increased with statistical significance in the Hyangpaeyayeongngtang group and the Fritillariae roylei bulbus group respectively, and the natural killer cell activity at the ratio of 50:1 and 10:1 of effector cells to target cells Hyangpaeyangyeongtang group was increased with statistical significance as compared with the control group. 7. Lymphocyte transformation was increased in the Hyangpaeyangyeong tang group and the Fritillariae roylei bulbus group respectively, as compared with the control group. 8. Productivity of interleukin-2 was increased in the Hyangpaeyangyecing tang group and the Fritillariae roylei bulbus group respectively, as compared with the control group. 9. Phagocytic activity was not shown any decrease in the Hyangpaeyangyeongtang group and the Fritillariae roylei bulbus group, as compared with the control group.
Oxygen supply into inside solid tumor is often diminished, which is called hypoxia. Many gene transcriptions were activated by hypoxia-inducible factor (HIF)-$1{\alpha}$. Here, we investigated the effect of hypoxia on paclitaxel-resistance induction in HeLa cervical tumor cells. When HeLa cells were incubated under hypoxia condition, HIF-$1{\alpha}$ level was increased. In contrast, paclitaxel-mediated tumor cell death was reduced by the incubation under hypoxia condition. Paclitaxel-mediated tumor cell death was also inhibited by treatment with DMOG, chemical HIF-$1{\alpha}$ stabilizer, in a dose-dependent manner. A significant increase in intracellular ROS level was detected by the incubation under hypoxia condition. A basal level of cell density was increased in response to 10 nM $H_2O_2$. HIF-$1{\alpha}$ level was increased by treatment with various concentration of $H_2O_2$. The increased level of HIF-$1{\alpha}$ by hypoxia was reduced by the treatment with N-acetylcysteine (NAC), a well-known ROS scavenger. Paclitaxel-mediated tumor cell death was increased by treatment with NAC. Taken together, these findings demonstrate that hypoxia could play a role in paclitaxel-resistance induction through ROS-mediated HIF-$1{\alpha}$ stabilization. These results suggest that hypoxia-induced ROS could, in part, control tumor cell death through an increase in HIF-$1{\alpha}$ level.
Annona muricata L (Annonaceae), commonly known as soursop has a long, rich history in herbal medicine with a lengthy recorded indigenous use. It had also been found to be a promising new anti-tumor agent in numerous in vitro studies. The present investigation concerns chemopreventive effects in a two-stage model of skin papillomagenesis. Chemopreventive effects of an ethanolic extract of A. muricata leaves (AMLE) was evaluated in 6-7 week old ICR mice given a single topical application of 7,12-dimethylbenza(${\alpha}$)anthracene (DMBA 100ug/100ul acetone) and promotion by repeated application of croton oil (1% in acetone/twice a week) for 10 weeks. Morphological tumor incidence, burden and volume were measured, with histological evaluation of skin tissue. Topical application of AMLE at 30, 100 and 300mg/kg significantly reduced DMBA/croton oil induced mice skin papillomagenesis in (i) peri-initiation protocol (AMLE from 7 days prior to 7 days after DMBA), (ii) promotion protocol (AMLE 30 minutes after croton oil), or (iii) both peri-initiation and promotion protocol (AMLE 7 days prior to 7 day after DMBA and AMLE 30 minutes after croton oil throughout the experimental period), in a dose dependent manner (p<0.05) as compared to carcinogen-treated control. Furthermore, the average latent period was significantly increased in theAMLE-treated group. Interestingly, At 100 and 300 mg/kg, AMLE completely inhibited the tumor development in all stages. Histopathological study revealed that tumor growth from the AMLE-treated groups showed only slight hyperplasia and absence of keratin pearls and rete ridges. The results, thus suggest that the A.muricata leaves extract was able to suppress tumor initiation as well as tumor promotion even at lower dosage.
Radixin, a member of the ERM (ezrin-radixin-moesin) family, plays important roles in cell motility, invasion and tumor progression. It is expressed in a variety of normal and neoplastic cells, including many types of epithelial and lymphoid examples. However, its function in glioblastomas remains elusive. Thus, in this study, radixin gene expression was first examined in the glioblastoma cells, then suppressed with a lentivirus-mediated short-hairpin RNA (shRNA) method.We found that there were high levels of radixin expression in glioblastoma U251cells. Radixin shRNA caused down-regulation of radixin gene expression and when radixin-silenced cells were implanted into nude mice, tumor growth was significantly inhibited as compared to blank control cells or nonsense shRNA cells. In addition, microvessel density in the tumors was significantly reduced. Thrombospondin-1 (TSP-1) and E-cadherin were up-regulated in radixin- suppressed glioblastoma U251 cells. In contrast, MMP9 was down-regulated. Taken together, our findings suggest that radixin is involved in GBM cell migration and invasion, and implicate TSP-1, E-cadherin and MMP9 as metastasis-inducing factors.
It is reported that a fermented soybean food, Doenjang, has srong antimutagenic and cytotoxic effect on cancer cells. This study investigated the effect of Chungkookjang, another traditional popular Korean soybean fermented food, on growth of cancer cells: HL-60, SNU-638 and MCF-7, and also its in vivo antitumorigenic effect in DMBA-induced mammary tumor rat model. For the in vitro study, Chungkookjang and steamed soybeans were extracted with ethanol and sequentially fractioned with 5 kinds of solvents differing in grades of polarity such as hexane, dichloromethane, ethylacetate, butanol and water. Almost all Chungkookjang extracts significantly inhibited the growth of HL-60 (human leukemic cancer cell), SNU-638 (human gastric cancer cell) and MCF-7 (human breast cancer cell) when compared to steamed soybean extracts. Butanol fraction of Chungkookjang extract especially showed a remarkable inhibitory effect in all the three kinds of cancer cells. To induce a mammary gland tumor, DMBA (50 mg/BW) was administered to 50 day-old female rats and followed by Chungkookjang or steamed soybean supplemented diets. Freezedried Chungkookjang powder (20% of diet in wet weight) was added to AIN-93G based diet for the Chungkookjang group of rats. Likewise, steamed soybean powder containing equal protein content to that of Chungkookjang powder was supplemented to soybean group of rats. At 13 weeks later, the mammary tumor incidence, average tumor number and tumor weight a rat were lower in Chungkookjang group compared to the control or soybean group. In conclusion, Chungkookjang showed a strong inhibitory effect on cancer cell growth in vitro, as well as a more preventive effect against chemically induced mammary tumorigenesis in vivo, while steamed soybeans did not. Therefore, these results suggest that Chungkookjang acquire its anticancer activity through the fermentation process.
Gui, Chengcheng;Morris, Carol D.;Meyer, Christian F.;Levin, Adam S.;Frassica, Deborah A.;Deville, Curtiland;Terezakis, Stephanie A.
Radiation Oncology Journal
/
v.37
no.2
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pp.117-126
/
2019
Purpose: The purpose of this study was to characterize and evaluate the clinical significance of volume changes of soft tissue sarcomas during radiation therapy (RT), prior to definitive surgical resection. Materials and Methods: Patients with extremity or pelvis soft tissue sarcomas treated at our institution from 2013 to 2016 with RT prior to resection were identified retrospectively. Tumor volumes were measured using cone-beam computed tomography obtained daily during RT. Linear regression evaluated the linearity of volume changes. Kruskal-Wallis tests, Mann-Whitney U tests, and linear regression evaluated predictors of volume change. Logistic and Cox regression evaluated volume change as a predictor of resection margin status, histologic treatment response, and tumor recurrence. Results: Thirty-three patients were evaluated. Twenty-nine tumors were high grade. Prior to RT, median tumor volume was 189 mL (range, 7.2 to 4,885 mL). Sixteen tumors demonstrated significant linear volume changes during RT. Of these, 5 tumors increased and 11 decreased in volume. Myxoid liposarcoma (n = 5, 15%) predicted decreasing tumor volume (p = 0.0002). Sequential chemoradiation (n = 4, 12%) predicted increasing tumor volume (p = 0.008) and corresponded to longer times from diagnosis to RT (p = 0.01). Resection margins were positive in three cases. Five patients experienced local recurrence, and 7 experienced distant recurrence, at median 8.9 and 6.9 months post-resection, respectively. Volume changes did not predict resection margin status, local recurrence, or distant recurrence. Conclusion: Volume changes of pelvis and extremity soft tissue sarcomas followed linear trends during RT. Volume changes reflected histologic subtype and treatment characteristics but did not predict margin status or recurrence after resection.
Background: Cancer registration data is used to understand the nation's cancer burden, and to provide significant baseline data for cancer control efforts, as well as, research on cancer incidence, mortality, survival, and prevalence. A system that approves, assesses, and manages the qualification of specialists, responsible for performing cancer registration, has not been developed in Korea. This study presents ways to implement a certification system designed for the qualification of tumor registrars in Korea. Materials and Methods: Requirements for implementing a certified tumor registrar qualification system were determined by reviewing the system for establishing qualifications in Korea and the American qualification system via the National Cancer Registrars Association (NCRA). Moreover, a survey was conducted on Korean medical records administrators, who had taken the U.S. Certified Tumor Registrar (CTR) examination, in order to review their opinions regarding these requirements. Results: This study verified the feasibility of a qualification examination based on the opinions of CTR specialists by determining the following: items, and the associated ratings, of the qualifications necessary to register individuals as certified tumor registrars in a private qualification system; status of human resources required for the examination or training processes; plans regarding the organization needed for management, and operation of qualifications, examination standards, subject areas, examination methods, examination qualifications, or education and training programs. Conclusions: The implementation of a certified tumor registrar qualification system will lead to enhanced job competency for specialists and a qualitative improvement of cancer registration data. It will also reliably foster human resources that will lay the groundwork needed to establish scientific and reasonable national cancer management policies.
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