Background: Inonotus obliquus, also known as Chaga, is a parasitic fungus growing on birches and used in traditional medicine (especially by Khanty people) to treat various health problems. In this ...study, we aimed to quantify the 3 metabolites frequently cited in literature, that is, betulin, betulinic acid, and inotodiol in the Chaga recently discovered in forests located in Normandy (France), and to compare their concentrations with Ukrainian and Canadian Chaga. This study also explores the cytotoxicity of the French Chaga against cancer-derived cells and transformed cells. Methods: A quantification method by HPLC-MS-MS (high-performance liquid chromatography–tandem mass spectrometry) of betulin, betulinic acid, and inotodiol was developed to study the French Chaga and compare the concentration of these metabolites with extracts provided from Chaga growing in Canada and Ukraine. This method was also used to identify and quantify those 3 compounds in other traditional preparations of Chaga (aqueous extract, infusion, and decoction). Among these preparations, the aqueous extract that contains betulin, betulinic acid, and inotodiol was chosen to evaluate and compare its cytotoxic activity toward human lung adenocarcinoma cells (A549 line) and human bronchial epithelial cells (BEAS-2B line). Results: French Chaga contains betulin and betulinic acid at higher levels than in other Chaga, whereas the concentration of inotodiol is greater in the Canadian Chaga. Moreover, the results highlighted a cytotoxic activity of the Chaga’s aqueous extract after 48 and 72 hours of exposure with a higher effect on cancer-derived cells A549 than on normal transformed cells BEAS-2B (P = 0.025 after 48 hours of exposure and P = 0.004 after 72 hours of exposure).
Most patients with localized breast cancer (LBC) who take adjuvant chemotherapy (CT) complain of fatigue and a decrease in quality of life during or after radiotherapy (RT). The aim of this ...longitudinal study was to compare the impact of RT alone with that occurring after previous CT on quality of life.
Fatigue (the main endpoint) and cognitive impairment were assessed in 161 CT-RT and 141 RT patients during RT and 1 year later. Fatigue was assessed with Functional Assessment of Cancer Therapy-General questionnaires, including breast and fatigue modules.
At baseline, 60% of the CT-RT patients expressed fatigue vs. 33% of the RT patients (p <0.001). Corresponding values at the end of RT were statistically similar (61% and 53%), and fatigue was still reported at 1 year by more than 40% of patients in both groups. Risk factors for long-term fatigue included depression (odds ratio OR = 6), which was less frequent in the RT group at baseline (16% vs. 28 %, respectively, p = 0.01) but reached a similar value at the end of RT (25% in both groups). Initial mild cognitive impairments were reported by RT (34 %) patients and CT-RT (24 %) patients and were persistent at 1 year for half of them. No biological disorders were associated with fatigue or cognitive impairment.
Fatigue was the main symptom in LBC patients treated with RT, whether they received CT previously or not. The correlation of persistent fatigue with initial depressive status favors administering medical and psychological programs for LBC patients treated with CT and/or RT, to identify and manage this main quality-of-life-related symptom.
Despite numerous guidelines, nearly one of two patients with cancer pain remains undertreated, thereby affecting their quality of life. Active patient involvement through Therapeutic Patient ...Education (TPE) is considered as a relevant strategy to overcoming hurdles in pain management. The aim of the EFFADOL study is to assess the effectiveness of a TPE program in improving cancer pain management.
The EFFADOL study is a stepped-wedge randomised controlled trial. A total of 260 cancer patients with unbalanced background pain will be randomised over the institutional level, i.e. stepped-wedge cluster design. Six clusters will be formed, one at the regional level of "Basse-Normandie" for patients receiving the educational approach by health providers already trained to TPE. Then, five additional centers will be gradually included at the national level, making it possible to compare the "conventional" management of pain (before medical staff training to TPE) with the educational approach (after being trained). The main study parameter is pain interference on daily life assessed with the self-administrated and validated Brief Pain Inventory questionnaire. Secondary objectives comprised the evaluation of patients' adherence to pain education program, the description of pain intensity, pain relief, analgesic adherence and pain emotional impact. Educational dimension of the program will be evaluated through the patients' acquisition of knowledge and skills about their pain and treatment as well as their self-efficacy to participate actively in pain management. The patient's feeling of pain changes will be measured. Finally, the satisfaction of participants and educators will be reported. We hypothetise active involvement of patients in TPE will lead to an improved pain management compared to standard care.
Analyzing the impact of a TPE program in cancer pain patients will improve their pain management and quality of life. We expect that the dissemination of our project educational approach through the French territory will be accompanied by long term change in clinical practices with mutual benefit to patients and caregiver-educators.
NCT03297723 , registered: 09/28/2017. Protocol version: Version n°1.1 dated from 2016/09/08.
Purpose
Older cancer patients are susceptible to long-term effects of chemotherapy, including cancer-related cognitive decline and impairments to quality of life. Taxane-based chemotherapies are ...associated with physical declines among older women and may negatively impact cognitive performance. We sought to examine whether changes in objective and subjective measures of cognitive performance and well-being differ among older breast cancer survivors as a function of taxane-based chemotherapy treatment regimens.
Methods
Individual-level data were pooled and harmonized from two large prospective studies of older (greater than 60 years) breast cancer survivors. Assessments were conducted prior to systemic therapy and up to 36 months after. Cognitive performance was assessed with objective (working memory, processing speed, and executive functions) and subjective tests and physical, emotional, and functional well-being were also assessed.
Results
One hundred and sixty-seven (M age = 67.3 years) women with 116 receiving chemotherapy with taxanes and 51 without taxanes contributed data. Declines in subjective cognition for both groups were significant between pre-treatment and 12-month follow-up. Significant improvements were seen on a measure of objective cognition (working memory) from 12 to 36 months. Measures of well-being improved from prior to systemic therapy to 12 months. Longitudinal changes across all measures did not vary as a function of receipt of taxane-based treatment.
Conclusion
Older women who received treatment with taxanes did not have greater declines in cognitive performance or well-being than women receiving other chemotherapy regimens. Despite older cancer survivors being at greater risk for negative outcomes, treatment with taxane-based chemotherapies does not appear to exacerbate these health consequences.
In patients with differentiated thyroid cancer (DTC), tumor burden of persistent disease (PD) is a variable that could affect therapy efficiency. Our aim was to assess its correlation with the 2015 ...American Thyroid Association (ATA) risk-stratification system, and its impact on response to initial therapy and outcome.
This retrospective cohort study included 618 consecutive DTC patients referred for postoperative radioiodine (RAI) treatment. Patients were risk-stratified using the 2015 ATA guidelines according to postoperative data, before RAI treatment. Tumor burden of PD was classified into three categories, i.e. very small-, small- and large-volume PD. Very small-volume PD was defined by the presence of abnormal foci on post-RAI scintigraphy with SPECT/CT or
FDG PET/CT without identifiable lesions on anatomic imaging. Small- and large-volume PD were defined by lesions with a largest size < 10 or ≥ 10 mm respectively.
PD was evidenced in 107 patients (17%). Mean follow-up for patients with PD was 7 ± 3 years. The percentage of large-volume PD increased with the ATA risk (18, 56 and 89% in low-, intermediate- and high-risk patients, respectively, p < 0.0001). There was a significant trend for a decrease in excellent response rate from the very small-, small- to large-volume PD groups at 9-12 months after initial therapy (71, 20 and 7%, respectively; p = 0.01) and at last follow-up visit (75, 28 and 16%, respectively; p = 0.04). On multivariate analysis, age ≥ 45 years, distant and/or thyroid bed disease, small-volume or large-volume tumor burden and
FDG-positive PD were independent risk factors for indeterminate or incomplete response at last follow-up visit.
The tumor burden of PD correlates with the ATA risk-stratification, affects the response to initial therapy and is an independent predictor of residual disease after a mean 7-yr follow-up. This variable might be taken into account in addition to the postoperative ATA risk-stratification to refine outcome prognostication after initial treatment.
Air quality in homes is a major concern in Europe, where people spend most of their time indoors. According to the World Health Organization, numerous houses are subject to dampness that can lead to ...mold growth, with associated health and economic consequences. Our goal was to characterize the human exposure to bioaerosols in French mold-damaged houses but also to study the effects of these bioaerosols as suffered by the inhabitants of these houses. A global approach including both field study and laboratory experimentation was used to investigate 48 mold-damaged homes. Among a wide fungal diversity, 101 viable species, Aspergillus versicolor, Penicillium chrysogenum and P. crustosum were observed as recurrent species and could be used as microbial indicators of indoor air quality. Statistical analyses highlighted a relationship between the concentrations of these recurrent molds and the levels of surface contamination by molds in homes. Fever, cough, dyspnea, flu-like symptoms were observed with several fungal strains (A. versicolor, P. chrysogenum and P. crustosum) or in relation to moldy odor. Relationships between particles of 2 to 15 µm diameter and headaches and dizziness were also observed. In our study, we identified a cutaneous effect (itching) in relationship to the airborne concentration of A. versicolor.
The mutagenic patterns of
and
extracts were evaluated. These strains of toxigenic
were collected from the agricultural environment. The Ames test was performed on
strains TA98, TA100 and TA102, ...without and with S9mix (exogenous metabolic activation system). These data were compared with the mutagenicity of the corresponding pure mycotoxins tested alone or in reconstituted mixtures with equivalent concentrations, in order to investigate the potential interactions between these molecules and/or other natural metabolites. At least 3 mechanisms are involved in the mutagenic response of these aflatoxins: firstly, the formation of AFB
-8,9-epoxide upon addition of S9mix, secondly the likely formation of oxidative damage as indicated by significant responses in TA102, and thirdly, a direct mutagenicity observed for higher doses of some extracts or associated mycotoxins, which does not therefore involve exogenously activated intermediates. Besides the identified mycotoxins (AFB
, AFB
and AFM
), additional "natural" compounds contribute to the global mutagenicity of the extracts. On the other hand, AFB
and AFM
modulate negatively the mutagenicity of AFB
when mixed in binary or tertiary mixtures. Thus, the evaluation of the mutagenicity of "natural" mixtures is an integrated parameter that better reflects the potential impact of exposure to toxigenic Aspergilli.
In this large cohort of Hodgkin's lymphoma survivors with long follow-up, we estimated the impact of treatment regimens on premature ovarian failure (POF) occurrence and motherhood, including safety ...of nonalkylating chemotherapy and dose-response relationships for alkylating chemotherapy and age at treatment.
The Life Situation Questionnaire was sent to 1,700 women treated in European Organisation for Research and Treatment of Cancer and Groupe d'Étude des Lymphomes de l'Adulte trials between 1964 and 2004. Women treated between ages 15 and 40 years and currently not using hormonal contraceptives (n = 460) were selected to assess occurrence of POF. Cumulative POF risk was estimated using the life-table method. Predictive factors were assessed by Cox regression analysis.
Median follow-up was 16 years (range, 5 to 45 years). Cumulative risk of POF after alkylating chemotherapy was 60% (95% CI, 41% to 79%) and only 3% (95% CI, 1% to 7%) after nonalkylating chemotherapy (doxorubicin, bleomycin, vinblastine, and dacarbazine; epirubicin, bleomycin, vinblastine, and prednisone). Dose relationship between alkylating chemotherapy and POF occurrence was linear. POF risk increased by 23% per year of age at treatment. In women treated without alkylating chemotherapy at age younger than 32 years and age 32 years or older, cumulative POF risks were 3% (95% CI, 1% to 16%) and 9% (95% CI, 4% to 18%), respectively. If menstruation returned after treatment, cumulative POF risk was independent of age at treatment. Among women who ultimately developed POF, 22% had one or more children after treatment, compared with 41% of women without POF.
Nonalkylating chemotherapy carries little to no excess risk of POF. Dose-response relationships for alkylating chemotherapy and age at treatment are both linear. Timely family planning is important for women at risk of POF.
Molds are ubiquitous biological pollutants in bioaerosols. Among these molds, the genus
is found in the majority of indoor air samples, and includes several species with pathogenic and toxigenic ...properties.
species in the series
remain little known despite recurrence in bioaerosols. In order to investigate their toxicity, we studied 22 isolates of clinical and environmental origin, corresponding to seven different species of the series
. Spore suspensions and ethyl acetate extracts prepared from fungal isolates were subjected to oxidative potential measurement using the dithiothreitol (DTT) test and cell survival measurement. The DTT tests showed that all species of the series
had an oxidative potential, either by their spores (especially for
) or by the extracts (especially from
). Measurements of cell survival of A549 and HaCaT cell lines showed that only the spore suspension containing 10
spores/mL of
caused a significant decrease in survival after 72 h of exposure. The same tests performed with mixtures of 10
spores/mL showed a potentiation of the cytotoxic effect, with a significant decrease in cell survival for mixtures containing spores of two species (on A549 cells,
= 0.05 and HaCaT cells,
= 0.001) or three different species (on HaCaT cells,
= 0.05). Cell survival assays after 72 h of exposure to the fungal extracts showed that
extract was the most cytotoxic (IC50 < 25 µg/mL), while
caused no significant decrease in cell survival.
ObjectiveIn patients with differentiated thyroid cancer (DTC), the stimulated serum thyroglobulin (Tg) level at radioiodine ablation is a known predictive factor of persistent disease. This ...prognostic value is based on data obtained after thyroid hormone withdrawal (THW), but little is known about this prognostic value after recombinant human TSH (rhTSH) stimulation and about the relationship between the stimulated Tg level and the burden of persistent tumor. We aimed to assess the impact of both radioiodine preparation modalities and persistent tumor burden on stimulated Tg levels.Design and methodsThe stimulated Tg level was measured at radioablation in 308 consecutive DTC patients without serum Tg antibodies. Of these, 123 (40%) were prepared with rhTSH and 185 with THW. Post-ablation scintigraphy included total-body scan and neck and thorax single photon emission computed tomography with computed tomography (SPECT–CT). During a mean follow-up of 43 months, persistent/recurrent disease (PRD) was found in 56 patients (18%). PRD was considered structural in the presence of lesions >1 cm and nonstructural otherwise.ResultsNonstructural PRD was more frequent in the rhTSH group than in the THW group (64 vs 26%, P=0.01). Stimulated Tg levels were lower after rhTSH than after THW in patients with (13.5 vs 99.5 ng/ml, P<0.01) and without (1.2 vs 3.2 ng/ml, P<0.001) PRD. Also, Tg levels were lower in nonstructural disease than in structural disease in both rhTSH (3.8 vs 127.0 ng/ml, P<0.01) and THW (13.0 vs 143.5 ng/ml, P<0.0001) patients. The best Tg cutoff to predict PRD was 2.8 in rhTSH and 28 ng/ml in THW patients.ConclusionBoth radioiodine preparation modalities and the burden of persistent tumor affect the stimulated Tg level at ablation.
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