Re-evaluating the role of pelvic radiation in the age of modern precision medicine and systemic therapy

The efficacy of pelvic radiation in the management of locally advanced stage rectal cancer has come under scrutiny in the context of modern precision medicine and systemic therapy as evidenced by recent clinical trials such as FOWARC(J Clin Oncol 2019;37:3223-3233),NCT04165772(N Engl J Med 2022;386:2363-2376),and PROSPECT(N Engl J Med 2023;389:322-334).In this review,we comprehensively assess these pivotal trials and offer additional insights into the evolving role of pelvic radiation in contemporary oncology.

Advancements in the Research of Gold Nanomaterials for Radiation Therapy Sensitization

Gold nanomaterials exhibit unique advantages in tumor radiotherapy sensitization due to their enhanced X-ray deposition capability, excellent biocompatibility, and superior chemical, electronic, and optical properties. To date, studies on gold nanomaterial-mediated radiosensitization have been reported, with related mechanisms including catalyzing reactive oxygen species (ROS) production, depleting intracellular glutathione (GSH), overcoming tumor hypoxia, and regulating cell cycles. This article will elaborate on the research progress of gold nanomaterial-mediated tumor radiotherapy sensitization and discuss its mechanisms and future research directions. In addition, the limitations of gold nanomaterials in clinical applications will be further discussed.

Ion emission from warm dense matter produced by irradiation with a soft x-ray free-electron laser

We report on an experiment performed at the FLASH2 free-electron laser(FEL)aimed at producing warm dense matter via soft x-ray isochoric heating.In the experiment,we focus on study of the ions emitted during the soft x-ray ablation process using time-of-flight electron multipliers and a shifted Maxwell–Boltzmann velocity distribution model.We find that most emitted ions are thermal,but that some impurities chemisorbed on the target surface,such as protons,are accelerated by the electrostatic field created in the plasma by escaped electrons.The morphology of the complex crater structure indicates the presence of several ion groups with varying temperatures.We find that the ion sound velocity is controlled by the ion temperature and show how the ion yield depends on the FEL radiation attenuation length in different materials.

Potential of non-Western medicines in chemoradiotherapy for cervical cancer

This editorial explores the potential integration of non-Western medicine into radiotherapy for cervical cancer.While radiotherapy remains a radical treatment for cervical cancer,its associated toxicity and decline in quality of life can significantly impact patients’lives.Currently,most treatments are supportive,with no specific treatment options available in Western medicine.Non-Western medicine,often less toxic and easier to administer,has shown promising results when used alongside radiotherapy for cervical cancer.Despite these potential benefits,challenges such as limited evidence and restricted application areas persist.While non-Western medicines may offer potential improvements in chemoradiotherapy outcomes for cervical cancer,further research is necessary to substantiate these benefits.

Current and future perspectives in the management and treatment of colorectal cancer

In this editorial,we reviewed the article by Fadlallah et al that was recently published in the World Journal of Clinical Oncology.The article provided a comprehensive and in-depth view of the management and treatment of colorectal cancer(CRC),one of the leading causes of cancer-related morbidity and mortality worldwide.The article analyzed the therapeutic modalities and their sequencing,focusing on total neoadjuvant therapy for locally advanced rectal cancer.It highlighted the role of immunotherapy in tumors with high microsatellite instability or deficient mismatch repair,addressing recent advances that have improved prognosis and therapeutic response in localized and metastatic CRC.Innovations in surgical techniques,advanced radiotherapy,and systemic agents targeting specific mutational profiles are also discussed,reflecting on how they revolutionized clinical management.Circulating tumor DNA has emerged as a promising tool for detecting minimal residual disease,prognosis,and therapeutic monitoring,solidifying its role in precision oncology.This review emphasized the importance of technological and therapeutic advancements in improving clinical outcomes and personalizing CRC treatment.

Prognostic impact of inflammatory and nutritional biomarkers in pancreatic cancer

Pancreatic cancer is usually associated with a poor prognosis.Surgery is the main curative treatment but pancreatic operations are aggressive and new tools that help clinicians to predict surgical and prognostic outcomes are necessary.Lu et al recently published a retrospective,single centre cohort study evaluating the impact of seven nutritional and inflammatory markers in pancreatic cancer surgical patients:The albumin-to-globulin ratio,prognostic nutritional index(PNI),systemic immune-inflammation index(SII),neutrophil-to-lymphocyte ratio(NLR),platelet-to-lymphocyte ratio(PLR),nutritional risk index,and the geriatric nutritional risk index.A significant correlation was found between the PNI,SII,NLR,and PLR and a hospital discharge of less than 15 days.In a univariable analysis,PNI,SII,NLR and PLR were significantly related to recurrence-free survival and,in a multivariable analysis PNI was associated with overall survival.Various meta-analyses corroborate the results in terms of prognosis but individual studies are discordant on their usefulness.Besides,the cut-off values for these markers vary significantly between studies and there are no clinical trials comparing them to identify the most relevant ones.These are limitations when implementing nutritional and inflammatory biomarkers into clinical practice and further studies are needed in order to answer these questions.

Validation of the prognostic model for palliative radiotherapy in older patients with cancer

BACKGROUND Older patients are more likely to have a poor performance status and comor-bidities.There is a reluctance to extensively investigate and treat older patients.As elderly individuals and patients with neoplasms each increase in number,palliative treatment of older patients is expected to grow as an issue.AIM To investigated the role of palliative radiotherapy in older patients and patients who were expected to demonstrate a therapeutic effect.METHODS From February 2019 to February 2022,33 patients aged≥80 years underwent palliative radiotherapy.The prognosis in palliative care study predictor(PiPS),palliative prognostic index(PPI),and delirium-palliative prognostic score(D-PaP)models were used for prognosis prediction.D-PaP scores calculated according to the doctor's prediction of clinical prediction of survival(CPS)were excluded and then analyzed for comparison.Radiation was prescribed at a dose of 2.5-7 Gy per fraction,up to a median of 39 Gy10(range,28-75 Gy10).RESULTS The median follow-up was 2.4 months(range,0.2-27.5 months),and 28 patients(84.8%)showed subjective symptom improvements following treatment.The 2-and 6-month survival rates of all patients were 91.5%and 91.5%,respectively.According to regression analysis,the performance status index,symptom type,and radiation dose all showed no significant correlation with the treatment re-sponse.When survival was expected for>55 days in the PiPS model,the 2-month survival rate was 94.4%.For patients with PPI and D-PaP-CPS values of 0-3.9 points,the 2-month survival rates were 90.0%and 100%,respectively.For patients with a score of≥4 points,the 2-month survival rates were 37.5%and 0%,res-pectively.Core Tip:This is a retrospective study to investigate the role of palliative radiotherapy in older patients and patients who were expected to demonstrate a great therapeutic effect.The prognosis in palliative care study predictor,palliative prognostic index,and delirium-palliative prognostic score models were used for prognosis prediction.Most of patients showed subjective symptom improvements following treatment.The prognosis prediction model showed good correlation with survival.In order to increase the therapeutic effectiveness in palliative radiotherapy,it is necessary to assess a patient's exact prognosis and select appropriate patients accordingly.INTRODUCTION The incidence of cancer is high among individuals 60-69 years old and is 11 times greater among those≥65-years-old compared to those<65-years-old.For this reason,about half of all cancer cases are diagnosed in individuals aged≥70 years,and older patients account for a large portion of the total population regarding the prevalence of cancer[1].Cancer is one of the most significant diseases in older patients.About 60%of all cancer-related deaths occur in older patients aged 70 years[1,2].Moreover,cancer accounts for about one-third of the causes of death in the elderly population[1,2].When choosing a cancer treatment,both the characteristics of the cancer and the overall health status of the patient,such as their general condition and any underlying diseases,should be considered[2].Older patients have a shorter life expectancy than younger patients;moreover,they typically have many accompanying underlying diseases and have a poorer general condition.For this reason,older patients are often rejected from receiving active testing and treatment services.Therefore,even if other factors,such as the underlying disease,are the same in young and old patients,older patients typically receive less treatment due to the simple fact that they are older[3].Palliative treatment is a treatment approach that improves the pain and symptoms of a patient and their quality of life.Although palliative treatment is applicable regardless of patient age and the type and severity of their disease,most patients requiring palliative treatment are cancer patients.Palliative radiotherapy is relatively effective for cancer patients and tends to be a well-tolerated treatment.Although some studies have reported the usefulness of palliative radiotherapy in elderly patients,a large number of patients and caregivers are not receiving treatment due to fears of treatment,the risks of side effects,and doubts about treatment effectiveness[1].Since actual age is not always associated with physical ability,the determination of treatment based solely on age can be an obstacle preventing appropriate treatment opportunities.The importance of palliative care is increasing due to the recent growth of the elderly population,as well as,the increase in cancer incidence,and the changes in traditional views or perceptions,such as a growing acceptance of the pursuit of a dignified death[4].Therefore,in this study,we investigated the role of palliative radiotherapy in older patients and in patients who are expected to show a great therapeutic effect.

Identifying adipocyte-derived exosomal miRNAs as potential novel prognostic markers for radiotherapy of esophageal squamous cell carcinoma

BACKGROUND Radiation resistance limits radiotherapy efficacy in esophageal squamous cell carcinoma(ESCC).The tumor microenvironment,particularly adipocytes,plays a role in promoting cancer progression.Extracellular vesicles and microRNAs(miRNAs)regulate gene expression and hold prognostic potential for esophageal carcinoma.Elucidating radioresistance mechanisms and identifying radiosensitization targets can help enhance radiotherapy efficacy for esophageal cancer.AIM To investigate the potential role of miRNAs derived from adipocyte exosomes as prognostic markers for radiotherapy efficacy in ESCC.METHODS Free adipocytes were isolated from human thoracic adipose tissue.A co-culture model of adipocytes and ESCC cells was established to observe colony formation and cell survival post-irradiation.ESCC cell apoptosis was assessed by flow cytometry.Western Blot and immunofluorescence assays were performed to evaluate DNA damage in ESCC cells post-irradiation.Adipocyte-derived exosomes were isolated by ultracentrifugation and identified by electron microscopy.A similar set of experiments was performed on ESCC cells to analyze cell survival,apoptosis,and DNA damage post-radiation exposure.Exosomes from adipose tissue and serum exosomes from ESCC patients pre-and post-radiotherapy were subjected to high-throughput miRNA-sequencing and validated using real-time quantitative polymerase chain reaction.The correlation between potential target miRNAs and the short-term prognosis of radiotherapy in ESCC was evaluated by receiver operating characteristic curve analysis.RESULTS Co-culturing adipocytes with ESCC cells enhanced radioresistance,as evidenced by increased colony formation.Adipocyte co-culture reduced ESCC cell apoptosis and DNA damage post-radiation.Adipocyte-derived exosomes similarly conferred radioresistance in ESCC cells,decreasing apoptosis and DNA damage post-irradiation.Highthroughput miRNA-sequencing identified miR-660-5p in serum and adipose tissue exosomes.Patients with high expression of serum exosome miR-660-5p showed poor prognosis after radiotherapy.CONCLUSION Adipocyte-derived exosomal miR-660-5p is a potential biomarker for evaluating radiotherapy efficacy in ESCC.

Impact of microplastics on the human digestive system:From basic to clinical

As a new type of pollutant,the harm caused by microplastics(MPs)to organisms has been the research focus.Recently,the proportion of MPs ingested through the digestive tract has gradually increased with the popularity of fast-food products,such as takeout.The damage to the digestive system has attracted increasing attention.We reviewed the literature regarding toxicity of MPs and observed that they have different effects on multiple organs of the digestive system.The mechanism may be related to the toxic effects of MPs themselves,interactions with various substances in the biological body,and participation in various signaling pathways to induce adverse reactions as a carrier of toxins to increase the time and amount of body absorption.Based on the toxicity mechanism of MPs,we propose specific suggestions to provide a theoretical reference for the government and relevant departments.

Role of radiation therapy in gastric adenocarcinoma

Outcomes in patients with gastric cancer in the United States remain disappointing, with a five-year overall survival rate of approximately 23%. Given high rates of local-regional control following surgery, a strong rationale exists for the use of adjuvant radiation therapy. Randomized trials have shown superior local control with adjuvant radiotherapy and improved overall survival with adjuvant chemoradiation. The benefit of adjuvant chemoradiation in patients who have undergone D2 lymph node dissection by an experienced surgeon is not known, and the benefit of adjuvant radiation therapy in addition to adjuvant chemotherapy continues to be defined. In unresectable disease, chemoradiation allows long-term survival in a small number of patients and provides effective palliation. Most trials show a benefit to combined modality therapy compared to chemotherapy or radiation therapy alone. The use of pre-operative, intra-operative, 3D conformal, and intensity modulated radiation therapy in gastric cancer is promising but requires further study. The current article reviews the role of radiation therapy in the treatment of resectable and unresectable gastric carcinoma, focusing on current recommendations in the United States.

Diffusion-weighted magnetic resonance imaging for predicting the response of rectal cancer to neoadjuvant concurrent chemoradiation

AIM:To evaluate the clinical value of diffusion-weighted magnetic resonance imaging(DW-MRI)in predicting the response of rectal cancer to neoadjuvant chemoradiation.METHODS:This prospective study was approved by our institutional review board,and informed consent was obtained from each patient.Fifteen patients(median age 56 years)with locally advanced rectal cancer were treated in our hospital from June 2006 to December 2007.All patients were stageⅢB-C according to the results of MRI and endorectal ultrasound examinations.All patients underwent pelvic irradiation with 45 Gy/25 fx per 35 days.The concurrent chemotherapy regimen consisted of capecitabine 625mg/m2,bid(Monday-Friday),and oxaliplatin 50 mg/m2,weekly.The patients underwent surgery 5-8 wk after the completion of neoadjuvant therapy.T downstaging was defined as the downstaging of the tumor from cT3to ypT0-2 or from cT4 to ypT0-3.Good regression was defined as TRG 3-4,and poor regression was defined as TRG 0-2.Diffusion-weighted magnetic resonance images were obtained prior to and weekly during the course of neoadjuvant chemoradiation,and the apparent diffusion coefficient(ADC)values were calculated from the acquired tumor images.RESULTS:Comparison with the mean pretreatment tumor ADC revealed an increase in the mean tumor ADC during the course of neoadjuvant chemoradiation,especially at the 2ndweek(P=0.004).We found a strong negative correlation between the mean pretreatment tumor ADC and tumor regression after neoadjuvant chemoradiation(P=0.021).In the T downstage and tumor regression groups,we found a significant increase in the mean ADC at the 2ndweek of neoadjuvant therapy(P=0.011;0.004).CONCLUSION:DW-MRI might be a valuable clinical tool to help predict or assess the response of rectal cancer to neoadjuvant chemoradiation at an early timepoint.

Role of radiation therapy in neoadjuvant era in patients with locally advanced rectal cancer

Surgery remains the primary determinant of cure in patients with localized rectal cancer, and total mesorectal excision is now widely accepted as standard of care. The widespread implementation of neoadjuvant shortcourse radiotherapy (RT) or long-course chemoradiotherapy (CRT) has reduced local recurrence rates from 25% to 40% to less than 10%; Preoperative RT in resectable rectal cancer has a number of potential advantages, most importantly reducing local recurrence, and down-staging effect. In this article making a comprehensive literature review searching the reliable medical data bases of PubMed and Cochrane we present all available information on the role of radiation therapy alone or in combination with chemotherapy in preoperative setting of rectal cancer. Data reported show that in locally advanced rectal cancer the addition of radiation therapy or CRT pre surgically has significantly improved sphincter prevention surgery. Moreover, the addition of chemotherapy to radiation therapy in preoperative setting has significantly improved pathologic complete response rate and loco-regional control rate without improvement in sphincter preserving surgery. Finally, the results of recently published randomized trials have shown a significant improvement of prevs postoperative CRT on local control; however, there was no effect on overall survival.

Role of stereotactic body radiation therapy for hepatocellular carcinoma

The integration of new technologies has raised an interest in liver tumor radiotherapy,with literature evolving to support its efficacy.These advances,particularly stereotactic body radiation therapy(SBRT),have been critical in improving local control or potential cure in liver lesions not amenable to first-line surgical resection or radiofrequency ablation.Active investigation of SBRT,particularly for hepatocellular carcinoma(HCC),has recently started,yielding promising local control rates.In addition,data suggest a possibility that SBRT can be an alternative option for HCC unfit for other local therapies.However,information on optimal treatment indications,doses,and methods remains limited.In HCC,significant differences in patient characteristics and treatment availability exist by country.In addition,the prognosis of HCC is greatly influenced by underlying liver dysfunction and treatment itself in addition to tumor stage.Since they are closely linked to treatment approach,it is important to understand these differences in interpreting outcomes from various reports.Further studies are required to validate and maximize the efficacy of SBRT by a large,multi-institutional setting.

Damage of nasal mucociliary movement after intensity-modulated radiation therapy of nasopharyngeal carcinoma

Background and Objective:Radiation usually results in paranasal sinusitis in patients with nasopharyngeal carcinoma (NPC), which influences patients' quality of life.This study aimed to determine the relationships between dose distribution in the nasal cavity and nasal mucous injury in patients with NPC treated by intensity-modulated radiation therapy (IMRT), and to find the tolerable radiation dose for the nasal mucous.Methods:Sixty-six patients with NPC treated by IMRT between October 2006 and November 2008 were enrolled.The irradiation dose in the nasal cavity was determined by the computer with the IMRT work platform.Mucociliary transport rate (MTR) was detected by modified saccharine test before IMRT, at the end of IMRT, and at 3, 6, and 12 months after IMRT.Results:The data were available for 129 nasal cavities.The cavities receiving a mean dose below or equal to 37 Gy showed substantial preservation of nasal mucous after IMRT.The MRT decreased to (62.82±38.59)%, (56.78±37.79)%, (64.05±39.37)%, and (71.13±39.55)% of pre-IMRT value at 4 time points after IMRT, with significant differences among the data (P<0.05).In contrast, when the cavities received a mean dose higher than 37 Gy, no significant differences in MTR among the time points were observed.At 3 months after IMRT, the MTR was the lowest (38.27% of pre-RT value).Conclusions:A mean radiation dose of ≤37 Gy for the nasal cavity is an optimal dose to protect the nasal cavity function.

Role of triamcinolone in radiation enteritis management

AIM:To investigate the role of triamcinolone in the management of acute and chronic enteritis caused by pelvic radiotherapy.METHODS:Twenty-eight patients with rectum adenocarcinoma or endometrium adenocarcinoma were studied.We compared the results of 14 patients treated with injected triamcinolone acetonide(TA)with those of 14 patients who were not treated with TA.For the TA group,40 mg of TA was injected intramuscularly on the 1st,11th and 21st d of radiotherapy;the control group received no injections.All of the study participants had a median age of 65 years,had undergone postoperative radiotherapy and were evaluated weekly using Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer Acute Morbidity Score Criteria,and complete blood counts for every 10 d.RESULTS:Triamcinolone was found to effectively prevent and treat radiation-induced acute gastrointestinal(enteritis)and genitourinary(cystitis)side effects(P=0.022 and P=0.023).For the lower GI side effect follow up,11 patients in the control group had Grade 2toxicity and 3 patients had Grade 1 toxicity.In the TA group,5 patients had Grade 2 toxicity and 9 patients had Grade 1 toxicity.For the genitourinary system side effect follow up,4 patients had Grade 2 toxicity and 6patients had Grade 1 toxicity.Additionally,2 patients had Grade 2 toxicity and 2 patients had Grade 1 toxicity.The neutrophil counts did not differ between the TA group and the control group.There was no meaningful difference between age groups and primary cancers.At the 12th mo of follow up,there were no differences between groups for chronic side effects.CONCLUSION:Triamcinolone is a moderately potent steroid,that is inexpensive and has a good safety profile.It would be beneficial for reducing medical expenses related to treatment of radiation induced enteritis.

Endoscopic and non-endoscopic approaches for the management of radiation-induced rectal bleeding

Pelvic radiation is a commonly utilized treatment for malignancy of the genitourinary and lower gastrointestinal tract. Radiation proctitis and the resultant clinical picture varies from asymptomatic to potentially life threatening. Similarly, treatment options also vary greatly, from medical therapy to surgical intervention. Commonly utilized medical therapy includes sucralfate enemas, antibiotics, 5-aminosalicylic acid derivatives, probiotics, antioxidants, short-chain fatty acids, formalin instillation and fractionated hyperbaric oxygen. More invasive treatments include endoscopic-based, focally ablative interventions such as dilation, heater and bipolar cautery, neodymium/yttrium aluminum garnet argon laser, radiofrequency ablation or argon plasma coagulation. Despite its relatively common frequency, there is a dearth of existing literature reporting headto-head comparisons of the various treatment options via a randomized controlled approach. The purpose of our review was to present the reader a consolidation of the existing evidence-based literature with the goal of highlighting the comparative effectiveness and risks of the various treatment approaches. Finally, we outline a pragmatic approach to the treatment of radiation proctitis. In light of the lack of randomized data, our goal is to pursue as least invasive an approach as possible, with escalation of care tailored to the severity of the patient's symptoms. For those cases that are clinicallyasymptomatic or only mildly symptomatic, observation or medical management can be considered. Once a patient fails such management or symptoms become more severe, invasive procedures such as endoscopically based focal ablation or surgical intervention can be considered. Although not all recommendations are supported by level I evidence, reported case series and single-institutional studies in the literature suggest that successful treatment with cessation of symptoms can be obtained in the majority of cases.

Radiation-induced sarcomas of the head and neck

With improved outcomes associated with radiotherapy, radiation-induced sarcomas(RIS) are increasingly seen in long-term survivors of head and neck cancers, with an estimated risk of up to 0.3%. They exhibit no subsite predilection within the head and neck and can arise in any irradiated tissue of mesenchymal origin. Common histologic subtypes of RIS parallel their de novo counterparts and include osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma/sarcoma nitricoxide synthase, and fibrosarcoma. While imaging features of RIS are not pathognomonic, large size, extensive local invasion with bony destruction, marked enhancement within a prior radiotherapy field, and an appropriate latency period are suggestive of a diagnosis of RIS. RIS development may be influenced by factors such as radiation dose, age at initial exposure, exposure to chemotherapeutic agents and genetic tendency. Precise pathogenetic mechanisms of RIS are poorly understood and both directly mutagenizing effects of radiotherapy as well as changes in microenvironments are thought to play a role. Management of RIS is challenging, entailing surgery in irradiated tissue and a limited scope for further radiotherapy and chemotherapy. RIS is associated with significantly poorer outcomes than stagematched sarcomas that arise independent of irradiationand surgical resection with clear margins seems to offer the best chance for cure.

Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer:Adjuvant 5-FU/cisplatin and chemoradiation with capecitabine

AIM： To evaluate the efficacy and toxicity of postoperative chemoradiation using FP chemotherapy and oral capecitabine during radiation for advanced gastric cancer following curative resection. METHODS： Thirty-one patients who had underwent a potentially curative resection for Stage Ⅲ and Ⅳ （M0） gastric cancer were enrolled. Therapy consists of one cycle of FP （continuous infusion of 5-FU 1000 mg/m^2 on d 1 to 5 and cisplatin 60 mg/m^2 on d 1） followed by 4500 cGy （180 cGy/d） with capecitabine （1650 mg/m daily throughout radiotherapy）. Four wk after completion of the radiotherapy, patients received three additional cycles of FP every three wk. The median follow-up duration was 22.2 mo. RESULTS： The 3-year disease free and overall survival in this study were 82.7% and 83.4%, respectively. Four patients （12.9%） showed relapse during follow-up. Eight patients did not complete all planned adjuvant therapy. Grade 3/4 toxicities included neutropenia in 50.2%, anemia in 12.9%, thrombocytopenia in 3.2% and nausea/ vomiting in 3.2%. Neither grade 3/4 hand foot syndrome nor treatment related febrile neutropenia or death were observed. CONCLUSION： These preliminary results suggest that this postoperative adjuvant chemoradiation regimen of FP before and after capecitabine and concurrent radiotherapy appears well tolerated and offers a comparable toxicity profile to the chemoradiation regimen utilized in INTo0116. This treatment modality allowed successful Ioco-regional control rate and 3-year overall survival.

Long-term outcomes of interventions for radiation-induced xerostomia:A review

Xerostomia, or dry mouth, is a significant problem affecting quality of life in patients treated with radiation therapy for head and neck cancer. Strategies for reduction of xerostomia burden vary widely, with options including: sialagogue medications, saliva substitutes, acupuncture, vitamins, hyperbaric oxygen,submandibular gland transfer, and acupuncture or associated treatments. In this review, we sought to evaluate long-term outcomes of patients treated with various interventions for radiation-induced xerostomia. A literature search was performed using the terms "xerostomia" and "radiation" or "radiotherapy"; all prospective clinical trials were evaluated, and only studies that reported 1 year follow up were included. The search results yielded 2193 studies, 1977 of which were in English. Of those, 304 were clinical trials or clinical studies. After abstract review, 23 trials were included in the review evaluating the following treatment modalities: pilocarpine(three); cevimeline(one); amifostine(eleven);submandibular gland transfer(five); acupuncture like transcutaneous electrical nerve stimulation(ALTENS)(one); hyperbaric oxygen(one); and acupuncture(one). Pilocarpine, cevimeline, and amifostine have been shown in some studies to improve xerostomia outcomes, at the cost of toxicity. ALTENS has similar efficacy with fewer side effects. Submandibular gland transfer is effective but requires an elective surgery, and thus may not always be appropriate or practical.The use of intensity-modulated radiation therapy, in addition to dose deescalation in select patients, may result in fewer patients with late xerostomia,reducing the need for additional interventions.

Role of PLC-PIP2 and cAMP-PKA Signal Pathways in Radiation-induced Immune-suppressing Effect

Objective The purpose of the present study was to observe the changes in CD4＋CD25＋Nrpl＋Treg cells after irradiation with different doses and explore the possible molecular mechanisms involved. Methods ICR mice and mouse lymphoma cell line （EL-4 cells） was used. The expressions of CD4, CD25, Nrpl, calcineurin and PKC-α were detected by flow cytometry. The expressions of TGF-131, IL-10, PKA and cAMP were estimated with ELISA. Results At 12 h after irradiation, the expression of Nrpl increased significantly in 4.0 Gy group, compared with sham-irradiation group （P〈0.05） in the spleen and thymus, respectively, when ICR mice received whole-body irradiation （WBI）. Meanwhile the synthesis of Interleukin 10 （IL-20） and transforming growth factor-β1 （TGF-β1） increased significantly after high dose irradiation （HDR） （〉 or = 1.0 Gy）. In addition, the expression of cAMP and PKA protein increased, while PKC-α, calcineurin decreased at 12h in thymus cells after 4.0 Gy X-irradiation. While TGF-β1 was clearly inhibited when the PLC-PIP2 signal pathway was stimulated or the cAMP-PKA signal pathway was blocked after 4.0 Gy X-irradiation, this did not limit the up-regulation of CD4＋CD25＋Nrpl＋Treg cells after ionizing radiation. Conclusion These results indicated that HDR might induce CD4＋CD25＋Nrpl＋Treg cells production and stimulate TGF-β1 secretion by regulating signal molecules in mice.