Epstein-barr virus DNAemia monitoring for the management of post-transplant lymphoproliferative disorder

Background

Post-transplant lymphoproliferative disorder (PTLD) is a potentially fatal complication of allogeneic hematopoietic cell transplantation (HCT). Epstein-Barr virus (EBV) reactivation (detectable DNAemia) predisposes to the development of PTLD.

Breast cancer local recurrence under the form of inflammatory carcinoma,treated with concurrent radiation and chemotherapy,a case report

The authors present a case report of a patient with breast cancer diagnosed in 2005, treated with conservative surgery, adjuvant chemotherapy and radiotherapy, followed by hormonal therapy until 2010, who relapsed under the form of inflammatory breast cancer in 2011. After tumor progression detected during primary systemic therapy, a concurrent radiation and radiosensitizing chemotherapy were proposed. There was a significant clinical response to this treatment, enabling curative chance with total mastectomy. The histological examination of the breast and regional lymph nodes revealed a complete response, since there was no evidence of residual tumor.There are few reports concerning concurrent radiotherapy and chemotherapy in locally advanced breast cancer, but it could be a suitable “loco regional rescue therapy” to further reduce tumor progression and allow curative surgery. Study of this treatment strategy in randomized clinical trials is warranted.     

Treatment outcomes and late toxicities of intensity-modulated radiation therapy for 1091 Japanese patients with localized prostate cancer

Aim

This study aimed to evaluate the treatment result of intensity-modulated radiation therapy (IMRT) in a large number of Japanese patients with prostate cancer.

Fine needle aspiration biopsy of a posttransplant lymphoproliferative disorder with pronounced plasmacytic differentiation presenting in the face. A case report

BACKGROUND: Posttransplant lymphoproliferative disorders (PTLDs) occur in fewer than 2% of transplant patients. However, as a group, 54% of PTLD patients die of these diseases. Presentation as only skin/superficial soft tissue nodules is rare, with this the second such reported case, and this is the only fine needle aspiration biopsy (FNAB) of such a case as well as the only FNAB of a plasmacytoid monomorphous/monoclonal PTLD. CASE: A 48-year-old, white male, seven years status post kidney transplantation, presented with a 2.5-cm mass in the skin/soft tissue anterior to the right maxillary sinus. FNAB showed a moderately cellular smear composed of discohesive cells, many with the morphology of plasma cells and some with the morphology of large lymphocytes. Flow cytometry showed these cells to be a monoclonal B-cell population, and a diagnosis of monomorphous/monoclonal PTLD was made. The diagnosis was subsequently confirmed by histology. The patient ultimately died. CONCLUSION: The clinical course of the present patient was grave as compared with the course of the other reported patient.     

Autophagy and chemotherapy resistance: a promising therapeutic target for cancer treatment

Induction of cell death and inhibition of cell survival are the main principles of cancer therapy. Resistance to chemotherapeutic agents is a major problem in oncology, which limits the effectiveness of anticancer drugs. A variety of factors contribute to drug resistance, including host factors, specific genetic or epigenetic alterations in the cancer cells and so on. Although various mechanisms by which cancer cells become resistant to anticancer drugs in the microenvironment have been well elucidated, how to circumvent this resistance to improve anticancer efficacy remains to be defined. Autophagy, an important homeostatic cellular recycling mechanism, is now emerging as a crucial player in response to metabolic and therapeutic stresses, which attempts to maintain/restore metabolic homeostasis through the catabolic lysis of excessive or unnecessary proteins and injured or aged organelles. Recently, several studies have shown that autophagy constitutes a potential target for cancer therapy and the induction of autophagy in response to therapeutics can be viewed as having a prodeath or a prosurvival role, which contributes to the anticancer efficacy of these drugs as well as drug resistance. Thus, understanding the novel function of autophagy may allow us to develop a promising therapeutic strategy to enhance the effects of chemotherapy and improve clinical outcomes in the treatment of cancer patients.     

Multi-strip silicon sensors for beam array monitoring in micro-beam radiation therapy

We present here the latest results from tests performed at the ESRF ID17 and ID21 beamlines for the characterization of novel beam monitors for Microbeam Radiation Therapy (MRT), which is currently being implemented at ID17. MRT aims at treating solid tumors by exploiting an array of evenly spaced microbeams, having an energy spectrum distributed between 27 and 600 keV and peaking at 100 keV. Given the high instantaneous dose delivered (up to 20 kGy/s), the position and the intensity of the microbeams has to be precisely and instantly monitored. For this purpose, we developed dedicated silicon microstrip beam monitors. We have successfully characterized them, both with a microbeam array at ID17, and a submicron scanning beam at ID21. We present here the latest results obtained in recent tests along with an outlook on future developments.     

Intraoperative radiation therapy opportunities for clinical practice normalization: Data recording and innovative development

Background

Intraoperative radiotherapy (IORT) refers to the delivery of a high dose of radiation at the time of surgery.

Aim

To analyze clinical and research-oriented innovative activities developed in a 17-year period using intraoperative electron-radiation therapy (IOeRT) as a component of treatment in a multidisciplinary approach for cancer management.

Materials and methods

From 01/1995 to 03/2012 IOeRT procedures were registered in a specific Hospital-based database. Research and developments in imaging and recording for treatment planning implementation are active since 2006.

Results

1004 patients were treated and 1036 IORT procedures completed. Median age of patients was 61 (range 5 months to 94 years). Gender distribution was male in 54% of cases and female in 46%. Disease status at the time of IORT was 796 (77%) primary and 240 (23%) recurrent. Cancer type distribution included: 62% gastrointestinal, 18% sarcoma, 5% pancreas, 2% paediatric, 3% breast, 77 7% oligotopic recurrences, 2% other. IORT technical characteristics were: Applicator size 5 cm 22%, 6 cm 21%, 7 cm 21%, 8 cm 15%, 9 cm 6%, 10 cm 7% 12 cm 5% 15 cm 3%. Electron energies: 6 MeV 19%, 8 MeV 15%, 10 MeV 15%, 12 MeV 23%, 15 MeV 19%, 18 MeV 6%, other 3%. Multiple fields: 108 (11%). Dose: 7.5 Gy 3%, 10 Gy 35%, 12 Gy 3%, 12.5 Gy 49%, 15 Gy 5%, other 5%.

Conclusion

An IORT programme developed in an Academic Hospital based on practice-oriented medical decisions is an attractive interdisciplinary oncology initiative proven to be able to generate an intensive clinical activity for cancer patient quality care and a competitive source of scientific patient-oriented research, development and innovation.     

Morphologic and immunophenotypic characterization of a cell line derived from liver tissue with epstein-barr virus associated post-transplant lymphoproliferative disease

Summary A B-cell line was established from the liver of an 11-yr-old boy with Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disease (PTLD). The cells were morphologically heterogenous, CD10 (CALLA) negative, and expressed several B-cell antigens, including CD23, in a manner reminiscent of lymphoblastoid cell lines (LCLs) reported in the literature. However, the cells also showed expression of the CD77 antigen, carried a 14q32+ chromosomal anomaly, and showed IgM-kappa immunoglobulin isotype restriction immediately after their outgrowth in culture. These latter properties are typically associated with Burkitt’s lymphoma cell lines rather than LCLs. Aberrant expression of the L60 antigen on these B-cells was found as additional evidence of altered growth regulation in these cells. EBV infection was demonstrated by the abundant expression of EBNA-2 and LMP viral antigens in culture. The cell line described should be useful in planning in vitro experiments designed to understand the factors that modulate the growth of PTLD in vivo.     

Combined effects of space flight factors and radiation on humans

The probability that a dose of ionizing radiation kills a cell is about 10,000 times the probability that the cell will be transformed to malignancy. On the other hand, the number of cells killed required to significantly impact health is about 10,000 times the number that must be transformed to cause a late malignancy. If these two risks, cell killing and malignant transformation, are about equal, then the risk that occurs during a mission is more significant than the risk that occurs after a mission. The latent period for acute irradiation effects (cell killing) is about 2-4 weeks; the latent period for malignancy is 10-20 years. If these statements are approximately true, then the impact of cell killing on health in the low-gravity environment of space flight should be examined to establish an estimate of risk. The objective of this study is to synthesize data and conclusions from three areas of space biology and environmental health to arrive at rational risk assessment for radiations received by spacecraft crews: (1) the increased physiological demands of the space flight environment; (2) the effects of the space flight environment on physiological systems; and (3) the effects of radiation on physiological systems. One physiological system has been chosen: the immune response and its components, consisting of myeloid and lymphoid proliferative cell compartments. Best-case and worst-case scenarios are considered. In the worst case, a doubling of immune-function demand, accompanied by a halving of immune capacity, would reduce the endangering dose to a crew member to around 1 Gy.     

Effects of microbeam radiation therapy on normal and tumoral blood vessels

Microbeam radiation therapy (MRT) is a new form of preclinical radiotherapy using quasi-parallel arrays of synchrotron X-ray microbeams. While the deposition of several hundred Grays in the microbeam paths, the normal brain tissues presents a high tolerance which is accompanied by the permanence of apparently normal vessels. Conversely, the efficiency of MRT on tumor growth control is thought to be related to a preferential damaging of tumor blood vessels.The high resistance of the healthy vascular network was demonstrated in different animal models by in vivo biphoton microscopy, magnetic resonance imaging, and histological studies. While a transient increase in permeability was shown, the structure of the vessels remained intact. The use of a chick chorioallantoic membrane at different stages of development showed that the damages induced by microbeams depend on vessel maturation. In vivo and ultrastructural observations showed negligible effects of microbeams on the mature vasculature at late stages of development; nevertheless a complete destruction of the immature capillary plexus was found in the microbeam paths. The use of MRT in rodent models revealed a preferential effect on tumor vessels. Although no major modification was observed in the vasculature of normal brain tissue, tumors showed a denudation of capillaries accompanied by transient increased permeability followed by reduced tumor perfusion and finally, a decrease in number of tumor vessels. Thus, MRT is a very promising treatment strategy with pronounced tumor control effects most likely based on the anti-vascular effects of MRT.     

Adoptive transfer of natural killer cells in combination with chemotherapy improves outcomes of patients with locally advanced colon carcinoma

Background

Despite the availability of multiple treatment strategies, patients with advanced colon carcinoma (CC) have poor prognoses. The aim of this study was to evaluate the efficacy and safety of natural killer (NK) cell therapy in combination with chemotherapy in patients with locally advanced CC.

Insights into apoptotic proteins in chemotherapy: quantification techniques and informing therapy choice

Introduction: Cancer is one of the leading causes of morbidity and mortality worldwide. A hallmark of cancer is evasion of apoptosis leading to tumor progression and drug resistance. Biomarker research has become a sign of the times, and proteins involved in apoptosis may be used for clinical diagnostic or prognostic purposes in cancer treatment. The recent progress in proteomic technology has triggered an emerging number of researchers to study the molecular mechanisms that regulate the apoptotic signal transduction pathways in cancer.

Areas covered: A PubMed search for ‘Proteomics’ and ‘cancer’ and ‘chemotherapy’ and ‘apoptosis’ has been conducted for literature until December 2017.

Results: The study of apoptotic protein signatures in cancer provides valuable information for more effective prognosis, response to therapy and the identification of novel drug targets. A huge number of bioinformatic tools are available to interpret raw data. For quantification, mass spectrometry is the most reliable technique.

Expert commentary: This field of research is, however, still in its infancy and more intensive research is warranted to explore the full potential of biomarkers for clinical use. Progress in this field is influenced by the detection limit of current quantification methods as well as patient and cancer inter-individual profiles.     

Caloric restriction augments radiation efficacy in breast cancer

Dietary modification such as caloric restriction (CR) has been shown to decrease tumor initiation and progression. We sought to determine if nutrient restriction could be used as a novel therapeutic intervention to enhance cytotoxic therapies such as radiation (IR) and alter the molecular profile of triple-negative breast cancer (TNBC), which displays a poor prognosis. In two murine models of TNBC, significant tumor regression is noted with IR or diet modification, and a greater regression is observed combining diet modification with IR. Two methods of diet modification were compared, and it was found that a daily 30% reduction in total calories provided more significant tumor regression than alternate day feeding. At the molecular level, tumors treated with CR and IR showed less proliferation and more apoptosis. cDNA array analysis demonstrated the IGF-1R pathway plays a key role in achieving this physiologic response, and multiple members of the IGF-1R pathway including IGF-1R, IRS, PIK3ca and mTOR were found to be downregulated. The innovative use of CR as a novel therapeutic option has the potential to change the biology of tumors and enhance the opportunity for clinical benefit in the treatment of patients with TNBC.     

国产两性霉素B抢先治疗血液病患者肺部侵袭性真菌感染的疗效与安全性分析

目的观察国产两性霉素B抢先治疗血液病患者侵袭性肺部真菌感染(以下简称IFI)的疗效与不良反应。方法回顾性分析我院2004年12月～2008年12月间,45例免疫功能低下IFI患者接受国产两性霉素B治疗的临床资料。结果 45例患者均应用两性霉素B治疗两周以上,最长应用时间为14周,中位数6周。总有效率为86.7%,不良反应主要有低钾血症、发热、转氨酶升高、肾功损害、胃肠道反应,根据WHO药物毒性分级标准均为I～II级毒性。结论国产两性霉素B对于血液病患者IFI临床诊断的抢先治疗疗效肯定,不良反应可耐受。     

Oxytocin in obsessive compulsive disorder

A double-blind, placebo-controlled study with syntocinon (oxytocin) was carried out in 12 patients, nine females and three males with obsessive compulsive disorder (OCD). Patients were treated by intranasal administration of oxytocin spray (18 IU per day) or placebo. No reductions in the number of obsessions or compulsive behaviors were observed in either treatment group. To evaluate whether a higher dosage would exert more beneficial effects, two additional patients were treated with a threefold higher dosage of oxytocin using an open design. In one patient a slight reduction in the number of checking rituals was observed, whereas in the other patient virtually no effect was observed. The results of this study do not support the hypothesis that oxytocin might be a potential anticompulsive agent.     

Solar UV-B and visible radiation in tropical forest gaps: measurements partitioning direct and diffuse radiation

Solar ultraviolet-B (UV-B) radiation penetrates plant canopies to a different degree than photosynthetically active radiation (PAR) because UV-B is diffused to a greater degree by the atmosphere. We measured both global (total) and diffuse solar radiation in canopy gaps of a semideciduous tropical forest in Panama. Measurements were simultaneously made in the UV-B and PAR wavebands. Compared to unobstructed measurements taken outside the forest, the sunlit portions of gaps were depleted in the proportion of UV-B relative to PAR, especially at midday. Shaded areas, in contrast, were always richer in UV-B relative to PAR, but the magnitude of the change varied greatly. Presumably this variation was due to the differences in the directional nature of diffuse solar UV-B radiation as compared to diffuse PAR. Measurements in the gaps showed substantial reductions in the proportion of radiation in the diffuse components of both the UV-B and PAR wavebands. However, because of the greater proportion of UV-B which is diffuse, it tended to predominate in shaded areas. Similar patterns were seen in measurements taken at temperate latitudes. Response of shade- and gap-dwelling plants to these high UV-B:PAR ratios has received little attention.     

The role of radiation-induced apoptosis as a determinant of tumor responses to radiation therapy

Ionizing radiation is an effective means of killing tumor cells. Approximately 50% of all American cancer patients are treated with radiotherapy at some time during the course of their disease, making radiation one of the most widely used cytotoxic therapies. Currently, much effort is focused on understanding the molecular pathways that regulate tumor cell survival following radiotherapy, with the long term goal of developing novel therapeutic strategies for specifically sensitizing tumors to radiation. At present, there is particular interest in the role of tumor cell apoptotic potential as a regulator of both intrinsic and extrinsic determinants of the response of tumors to radiation therapy. Here we review what is currently known about the role of apoptosis as a mechanism of tumor cell killing by ionizing radiation and the relative contribution of apoptosis to cellular radiosensitivity and the ability to control human cancers using radiotherapy. The following topics will be discussed: (1) radiation-induced apoptosis in normal and malignant cells, (2) clinical findings with respect to apoptosis in human cancers treated with radiotherapy, (3) the contribution of apoptosis to intrinsic radiosensitivity in vitro, (4) the relevance of apoptosis to treatment outcome in experimental tumor models in vivo and (5) the potential of exploiting apoptosis as a means to improve the therapeutic efficacy of radiotherapy.