Abstract: Objective: HOTAIR, a long intervening non-coding Hox transcript antisense intergenic RNA, negatively regu- lates transcription on another chromosome and is reported to reprogram chromatin organization and promote tu- mor progression. Nevertheless, little is known about its roles in the development of radiation therapy of lung cancer. In this study, we established a xenografed model of Lewis lung carcinoma in C57BL/6 mice and investigated the possible involvement of HOTAIR in this radiotherapy. Methods: C57BL/6 mice were subcutaneously transplanted with Lewis lung carcinoma cells and locally irradiated followed by measurement in tumor volume. Levels of HOTAIR and WIF-1 mRNA expression were determined by using Quantitative Real-Time PCR. Levels of WIF-1 and β-catenin were determined by using western blot assay. Cell viability was evaluated by MTT assay. Cell apoptosis was exam- ined by using TUNEL assay. Results: In mice bearing Lewis lung carcinoma tumor, local radiotherapy suppressed tumor growth and it also reduced level of HOTAIR but increased WIF-1 expression. When HOTAIR was overexpressed, radio-sensitivity was reduced. In vitro experiments, irradiation inhibited HOTAIR transportation to the nucleus. However, it was reversed by over-expressed HOTAIR. Cells transfected with pcDNA-HOTAIR or siRNA-HOTAIR resulted in decline or increase in radiosensitivity, which was abrogated by co-tansfected with siRNA-β-catenin. Conclusion: Radiotherapy induced Lewis lung cancer cell apoptosis via inactivating β-catenin mediated by upregulated HOTAIR.
The bacterial population in the cecum has been reported to be more abundant in Firmicutes, the phylum of SCFA-producing gut bacteria, relative to feces (48). Therefore, we carried out 16S rRNA marker gene sequencing and confirmed that the levels of gram-pos- itive SCFA-producing bacteria were substantially reduced following treatment with vancomycin alone. Fecal samples from mice treated with 0.5 g/L oral vancomycin were sequenced and compared with samples from untreated control mice. As expected, we found that vancomycin treatment induced major alterations in the bacterial community composition, including elimination of the majority of gram-positive taxa together with some impact on gram-negative taxa (Figure 6E). As a result, the number of bacterial taxa found in the vancomycin-treated group was 4 times lower than that of the untreated controls (P = 0.01) (Figure 6F). The composition of the bacterial community was altered consistently by vancomycin treat- ment, as indicated by an analysis of unweighted UniFrac distance, which is a measure of community dissimilarity between samples. Sample distances within the control and vancomycin treatment groups were drastically lower than the between-group distances (P < 0.001) (Figure 6G).
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Given all the lifestyle, environmental and genetic factors which play a role in cancer risk, radiotherapy is simply one of the many contributing factors to second primary development. Larger scale observational studies with longer fol- low up time are required to further assess the risk of radiation-induced malig- nancies, especially in younger patient populations. With the current data, the benefits of radiation therapy in appropriate selected patients still outweigh the risks and side effects of treatment. While an effort should be taken to reduce the amount of radiation a patient is subjected to, cancer treatment and prevention with appropriate therapy should always take priority with an appreciation of pa- tient risk factors and latency periods.
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grade III and IV mucositis is diagnosed based on its clinical presentation of superficial ulcerations covered by pseudomembranes, that are very painful to be rubbed off. These pseudomembranous ulcerations are to be differentiated from pseudomembranous candidosis, consisting of whitish, easy to rub off, pseudomembranes. Again, the laboratory isolation of yeasts from smears, taken from the lesions, may be helpful, but is not critical for diagnosis. Pseudomembranous candidosis may be superimposed on the pseudomembranous ulcerations of mucositis and, in these cases, the differentiation is difficult. Severe mucositis is important to be differentiated from the clinically identical, herpes simplex virus-1 reactivation and infection in neutropenic patients. Herpetic infection, if not diagnosed and treated promptly, may further aggravate mucositis and delay may further aggravate mucositis and delay healing, thus compromising the antineoplastic protocol (Sonis et al., 1999). The correlation co-efficient of the head and neck cancer oral stomatitis domain and the WHO scale was 0.58 and hence being commonly use (Sylvester, 1980). In our present study the WHO mucositis grading system was utilized which showed that every patient had a significant increase in the gradation of mucositis mostly starting from the 2nd week of treatment and by the end of the 4th week, grade III or grade IV mucositis (Figure 1). The Wilcoxon signed rank test showed that there was a statistically significant difference between the clinical grade of mucositis between week 1 and week 2 (Z-4.873), week 1 and week 3 (Z-4.890) and also week 1 and week 4 (Z-4.928) as per Table 1. Our present study consists of 30 patients of whom 25 were males and 5 females consisting of 83% and 17% respectively. Carcinoma of tongue, carcinoma alveolus and carcinoma of buccal mucosa were major carcinoma. In our study, approximately 63% of patients developed severe form of mucositis as per the WHO mucositis grading scale. In the total of 18 patients who underwent chemo-radiotherapy about 10% of patients developed grade III mucositis by the end of the 3rd week of therapy.
Surgical resection is regarded as a standard treatment for early NSCLC while radiotherapy has been offered to patients who are not suitable for surgery due to medic- ally inoperable factors such as poor pulmonary function or severe cardiovascular dysfunction . SBRT is cur- rently defined as a technique for delivering external beam radiotherapy with a high degree of accuracy to an extra-cranial target, using high doses per fraction, and now considered as the first-line treatment option for medically inoperable patients affected by early NSCLC . For peripheral lung tumors, low treatment-related toxicity rates have been confirmed in prospective trials, as these tumors are mainly surrounded by lung tissue . On the other hand, SBRT for central located tumors (< 2 cm from the main bronchus) has a potential risk of developing severe, potentially life-threatening toxicities because of the proximity of the target field to critical or- gans such as the main bronchus, the esophagus, and the heart . When SBRT is employed to treat centrally lo- cated NSCLCs, the esophagus is typically one of the most crucial organs at risk owing to its close proximity to the radiation field. The adverse effects on the esopha- gus are well-known complications of SBRT for centrally located lung tumors. These esophageal complications range from esophagitis to esophagus ulcer resulting in stricture, perforation, and/or tracheo-esophageal fistula, and the frequency of grade 1–2 and over grade 3 toxicity according to the Common Terminology Criteria for Ad- verse Events has been reported as up to 12.8% and up to
The radiation-enhanced efficacy of therapy mediated by OAds might also be due the ioni- zing radiation increasing viral replication . Cross-resistance is theoretically unlikely beca- use the mechanisms of oncolytic virus and ionizing radiation are independent of one an- other, consequently minimizing the possibility of treatment-resistant tumor cells developing. Here, we examined the efficacy of treating RCC cells with gene therapy mediated by F5/ 35-ZD55 combined with radiotherapy. Wes- tern blotting confirmed higher E1A protein expression in cells treated with F5/35-ZD55 alone or a combination of F5/35-ZD55 and radiotherapy. Our results indicate that F5/35- ZD55 replicates efficiently in Ketr-3 RCC ce- lls. Consistent with this finding, the MTT ass- ay showed that the combined F5/35-ZD55 and radiotherapy induced cytopathic effects in Ketr-3 cells specifically. Furthermore, F5/35- ZD55 and radiotherapy significantly inhibited tumor growth when compared with F5/35-ZD- 55 treatment or radiotherapy alone.
Background : Radiation-induced gliomas of the spinal cord are rare late complica- tions of spinal cord irradiation that typically occur in patients treated at younger ages. Aim : Raise awareness of radiation induced high grade gliomas with a case presentation and a review of the literature. Case Presentation : A 50-year-old male with Stage IVA squamous cell carcinoma of the oropharynx was treated with external beam radiotherapy with a complete response. Seven years later, he presented with a cervical spinal cord mass on MRI. An open biopsy was performed. Pathology re- vealed an intramedullary WHO grade IV astrocytoma, ( i . e ., glioblastoma multi- forme) of the cervical spine that fulfilled the criteria for a radiation-induced malig- nancy. Conclusions : Review of the literature suggests that radiation-induced gliomas tend to be high grade and may occur at the periphery of an irradiated field. Radia- tion-induced gliomas of the spinal cord are a serious complication of radiotherapy that may occur in older patients with head and neck cancers, but are so rare that it should not affect treatment decisions.
PI3K, AKT1, ERK1 and JNK had been reported to be the downstream signals of TGF-β. An ex vivo study found that inhibiting PI3K/Akt was able to block cell prolifera- tion, increase of α-SMA expression and collagen pro- duction induced by TGF-β, which demonstrated the dominant roles of the PI3K/Akt pathway in the prolifera- tion and differentiation process of lung fibroblast . In addition, Caraci et al. demonstrated that TGF-β1 induced α-SMA expression and collagen production in human lung fibroblasts via ERK1/2 pathway activation, GSK-3β inhibition, and nuclear β-catenin translocation . Utsugi et al.  suggested that TGF-β1-induced con- nective tissue growth factor (CTGF) mRNA expression was mediated through the JNK-dependent pathway . Our current study showed that increased VTN promoted the phosphorylated levels of ERK, AKT and JNK, which indicated that VTN overexpression activated the fibrosis regulatory pathway dominated by TGF-β to further pro- mote the production of collagens. In the in vivo study, the mice infected with VTN-overexpressed lentivirus exhib- ited enhanced TGF-β1 production which coupled with increased expression of α-SMA. In contrast, the mice infected with VTN-si-NRA lentivirus decreased TGF-β1 and suppressed transcription of α-SMA. These results, together with the data mentioned above, suggested that VTN might promote the differentiation of lung fibro- blasts to form a myofibroblast phenotype through up- regulation expression of TGF-β1 and increasing the transcription of α-SMA.
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The primary outcome of interest in this study is a reduc- tion of pain of 2 points at 6 weeks since baseline. The literature shows that in patients with conventional radio- therapy the percentage of patients with pain reduction ranges from 66 % to 72 %. We assume that the percent- age of patients with pain reduction is 70 % in the group with conventional radiotherapy compared to 85 % in the group with stereotactic radiotherapy. Therefore, 135 pa- tients are needed in each group to obtain a power of 80 % (Fisher-exact test, two-sided, alpha = 0.05). We adjust for a drop-out rate of 30 % and will include a total of 386 pa- tients. The primary analysis will be the comparison be- tween the two treatment arms of the proportion of patients with pain reduction, defined as a decrease in pain score of at least 2 points from initial pain score, at 6 weeks. Time to pain progression, radiation-induced fracture and/ or death will be calculated from date of randomization to the documentation. For the calculation of response, no fixed time interval from the date of randomization will be applied. Response of treatment will be calculated if at least two successive follow-up pain scores are available.
It is one of the main radiosensitizers studied around the world. Studies have shown that gemcitabine compliments both radiation and cisplatin. In a phase II study by pattaranutaporn et al, gemcitabine was delivered at 300 mg/m 2 weekly during radiotherapy for 5 weeks in patients with FIGO Stage III.B cervical cancer. This regiment was tolerated well. At follow up, CR was achieved in all except 2 and at a median follow up of 20 months the DFS and OS were 84% and 100% respectively . Though gemcitabine has shown excellent local control rates, the toxicity when combined with cisplatin is on the higher side as gemcitabine sensitizes both radiation and cisplatin. This was seen in a study by Alvarez et al [96, 97].
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PSMA is a glutamate carboxypeptidase II with folate hydrolase 1 (FOLH1) and N-acetylated α-linked acidic dipeptidase (NAALADase) activities [28, 29]. The car- boxypeptidase activity and an expression pattern analogue to that of pro-angiogenic acting CD13/APN molecule strongly suggest the regulating role of PSMA during the angiogenic processes in tumor tissue [30, 31]. As shown by Conway et al., PSMA participates in laminin-specific integrin signaling and in regulation of cytoskeletal dynam- ics which are required for angiogenesis in vivo and for invasiveness of endothelial cells in vitro. Recent in vitro studies suggest the endothelial PSMA expression to be induced by tumor-released factors [32, 33]. In this study, we found that the TNBC cells MDA-MB231 led the endo- thelial cells to generate tubes at a level comparable to VEGF-containing medium. In contrast, the NTNBC cells MCF-7 did not show any pro-angiogenic effect, suggesting that the stimulating potential is not related to the PSMA expression. These data correspond to the pathological profile of TNBC characterized by aggressive and highly metastatic progression. As shown by Wang et al., the TNBC cells produce higher level of VEGF and MMP-9
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The resulting salivary gland hypofunction and xerostomia arising from radiotherapy for HNC can cause a serious diseased condition. The stomatologic complications could depend on the type of cancer treatment and the cumulative radiation dose to the gland tissue. They can be reversible or irreversible, transient, or enduring. The best approach to manage the radiotherapeutic patient begins with a careful clinical assessment of the individual case, followed by pre- ventive therapy aimed to reduce oral complications when possible. Therefore, the clinician must keep this kind of patients under careful control in order to palliate the symp- toms of xerostomia and improve their quality of life.
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received antiemetic therapy along with CRT to prevent chemotherapy-induced nausea and vomiting. Because of dysphagia and prolonged nausea due to the radiotherapy, a nasogastric tube was inserted on day 23 of CRT. En- teral nutrition was administered by intermittent injec- tion three times a day, and the nasogastric tube was clamped overnight after the last daily administration of enteral nutrition. On the evening of day 27, the patient vomited, which was followed by severe left chest pain ra- diating to the back and the upper abdomen. During the vomiting episode, the nasogastric tube was unintention- ally removed along with vomitus. A physical exam was negative for rebound tenderness in the abdomen; the symptoms were relieved by analgesics; and the patient was observed overnight. His symptoms returned in the morning, and his temperature was 38.2 °C. Laboratory testing showed an intense inflammatory response (CRP 8.02 mg/dL). Contrast-enhanced computed tomography (CT) revealed extensive mediastinal emphysema extending from the neck to the gastric cardia, a small amount of left pleural effusion, and no pneumothorax (Fig. 1b, c). Boerhaave syndrome was suspected at this point in the patient’s clinical course. Since his general status and vital signs were stable, he underwent esopha- gography to confirm the diagnosis and aid in treatment planning. Since reinsertion of a nasogastric tube was dif- ficult, the esophagogram was obtained after the patient ingested contrast medium orally while being observed
Our study, as many others, is certainly limited by the small study population and the retrospective design. Fur- thermore different treatment protocols reduce the com- parability of treatment outcomes. Prospective trials would be desirable for further evaluation but the first planned prospective and randomized study (initiated by the Baro- medical Research Foundation) was cancelled because of poor recruitment (NCT00134628). Nevertheless, we be- lieve that our results show the long-term efficiency and safety of this therapy option in patients suffering from radiation- and cyclophosphamide-induced haemorrhagic cystitis.
Adjuvant radiotherapy following breast conserving surgery has been an important component of the standard of care for early breast cancer. Improvements in breast cancer care have resulted in a substantial reduction in local relapse rates over recent decades.mean that local relapse rates have fallen substantially over recent decades. Although the proportional benefits of adjuvant radiotherapy are similar for different prognostic risk groups of patients, the absolute benefits depend on risk of relapse and therefore vary considerably between prognostic groups. Radiotherapy is not without risk and for some patients at very low risk of relapse the risks of radiotherapy may outweigh the benefit leading to potential overtreatment.
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To understand the role of autophagy in RT- induced TC cells apoptosis, autophagy level was quantified by FACS following MDC staining. X-ray irritation induced an increase of MDC positive SW579 cell population, which was respectively increased to 6.33%, 22.8% and 11.67% at 12, 24 and 48 h (Figure 2A). Further, the intense punctuate MDC fluorescence which represented the autophagic vacuoles were clearly increased in X-ray irritated SW579 cells (Figure 2B). Moreover, the expression of auto- phagy associated protein Beclin-1 and conver- sion of LC3 I to LC3 II were raised by radiation treatment (Figure 2C). These dates indicate that autophagy could be induced by RT in TC cells.
Extraction was performed by two reviewers. Disagreements were resolved by discussion. We contacted the original study researchers for indistinct data and removed the data from stage II NPC patients. The following information was extracted: first author, publication year, patient number, inclusion period, random method, treatment regimen, and outcomes. The effi- cient outcomes were overall response rate (ORR), complete response rate (CRR), and OS. As for the toxic outcomes, data on grade 3–4 adverse events of hematologic toxicity, gastrointestinal reaction, radiation-induced oral mucositis, and radiodermatitis were extracted. If the study reported relevant adverse events separately, for example, nausea, vomiting, and diarrhea, the higher event rate was used to approximate the overall events. Among the 15 studies, 1 study utilized Common Terminology Criteria for Adverse Events criteria 3.0 for adverse events, and the rest utilized the World Health Organization criteria. However, the evaluation standard is very similar in these two criteria for adverse events. Thus, these data could be combined in this meta-analysis.
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The included studies were comparative studies, including both retrospective and prospective studies, that compared radiotherapy, including SBRT/SABR, with surgery, includ- ing lobectomy, segmentectomy, or wedge resection, in patients with T1-3N0M0 NSCLC. The clinical stages of NSCLC ranged from I to II. When multiple groups were pres- ent in an individual study, we only selected the comparison between lobectomy plus segmentectomy plus wedge resec- tion and SBRT/SABR. In some studies on SBRT/SABR in propensity-matched analysis, we selected the comparison
DOI: 10.4236/jct.2019.108051 628 Journal of Cancer Therapy ate only 3% risk of necrosis. Normalized total dose of conventional re-irradiation was lower than those used in either stereotactic radiosurgery or fractionated ste- reotactic radiotherapy . Radionecrosis happened at normalized total doses more than 100 Gy. There was no association between risk of radionecrosis and interval time between treatment courses. Due to limiting normal tissue irradia- tion, re-irradiation using stereotactic and conformal techniques is safe and asso- ciated with limited risk of radionecrosis .
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and targeted therapeutic targets have not been identified. For early stage TNBC, surgical treat- ment combined with radiotherapy improves local control and is currently the best treatment available. However, for patients with advanced stage TNBC, radiotherapy has not significantly affected prognosis . Moreover, neopathy of radiotherapy remains a cause of increased mortality . The potential side effects of che- motherapy should also be considered, and these include immunosuppression and toxicity to kidneys, liver, lung, and heart. Unfortunately, these side effects remain difficult to overcome. Consequently, immunotherapy represents an attractive option for cancer treatment due to its low toxicity and high specificity . Moreover, it has been demonstrated that cell immuno- therapy combined with conventional treatment can improve treatment outcomes . The mechanism responsible for this improvement may derive from the synergistic effects of the- se two approaches. For example, chemothera- py not only kills and/or slows the growth of can- cer cells, but it can also increase the sensitivity of tumor cells’ response to immune effector cells. Meanwhile, immunotherapy can restore an immune system which is compromised by chemotherapy and can also stimulate antitu- mor immunity . Currently, DC-CIK cell treat- ment is widely used for the treatment of cancer patients. Antigen-presenting DCs are able to activate naive CD4 + T helper cells and they