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Background: Theobroma cacao, the cocoa tree, is a tropical crop grown for its highly valuable cocoa solids and fat which are the basis of a 200-billion-dollar annual chocolate industry. However, the long generation time and difficulties associated with breeding a tropical tree crop have limited the progress of breeders to develop high-yielding disease-resistant varieties. Development of marker-assisted breeding methods for cacao requires discovery of genomic regions and specific alleles of genes encoding important traits of interest. To accelerate gene discovery, we developed a gene atlas composed of a large dataset of replicated transcriptomes with the long-term goal of progressing breeding towards developing high-yielding elite varieties of cacao., Results: We describe the creation of the Cacao Transcriptome Atlas, its global characterization and define sets of genes co-regulated in highly organ- and temporally-specific manners. RNAs were extracted and transcriptomes sequenced from 123 different tissues and stages of development representing major organs and developmental stages of the cacao lifecycle. In addition, several experimental treatments and time courses were performed to measure gene expression in tissues responding to biotic and abiotic stressors. Samples were collected in replicates (3-5) to enable statistical analysis of gene expression levels for a total of 390 transcriptomes. To promote wide use of these data, all raw sequencing data, expression read mapping matrices, scripts, and other information used to create the resource are freely available online. We verified our atlas by analyzing the expression of genes with known functions and expression patterns in Arabidopsis (ACT7, LEA19, AGL16, TIP13, LHY, MYB2) and found their expression profiles to be generally similar between both species. We also successfully identified tissue-specific genes at two thresholds in many tissue types represented and a set of genes highly conserved across all tissues., Conclusion: The Cacao Gene Atlas consists of a gene expression browser with graphical user interface and open access to raw sequencing data files as well as the unnormalized and CPM normalized read count data mapped to several cacao genomes. The gene atlas is a publicly available resource to allow rapid mining of cacao gene expression profiles. We hope this resource will be used to help accelerate the discovery of important genes for key cacao traits such as disease resistance and contribute to the breeding of elite varieties to help farmers increase yields., (© 2024. The Author(s).)

The international radiotherapy (RT) expert panel has revised and updated the RT guidelines that were accepted in 2020 at the 4th Hungarian Breast Cancer Consensus Conference, based on new scientific evidence. Radiotherapy after breast-conserving surgery (BCS) is indicated in ductal carcinoma in situ (stage 0), as RT decreases the risk of local recurrence (LR) by 50-60%. In early stage (stage I-II) invasive breast cancer RT remains a standard treatment following BCS. However, in elderly (≥70 years) patients with stage I, hormone receptor-positive tumour, hormonal therapy without RT can be considered. Hypofractionated whole breast irradiation (WBI) and for selected cases accelerated partial breast irradiation are validated treatment alternatives to conventional WBI administered for 5 weeks. Following mastectomy, RT significantly decreases the risk of LR and improves overall survival of patients who have 1 to 3 or ≥4 positive axillary lymph nodes. In selected cases of patients with 1 to 2 positive sentinel lymph nodes axillary dissection can be substituted with axillary RT. After neoadjuvant systemic treatment (NST) followed by BCS, WBI is mandatory, while after NST followed by mastectomy, locoregional RT should be given in cases of initial stage III-IV and ypN1 axillary status., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Polgár, Kahán, Ivanov, Chorváth, Ligačová, Csejtei, Gábor, Landherr, Mangel, Mayer and Fodor.)

The primary aim of AVACONT was to collect data in the course of routine oncological care from patients with metastatic colorectal cancer (mCRC) treated with bevacizumab supplemented fluoropyrimidine-based chemotherapy doublet in an open, multicentre, observational study in Hungary. Primary endpoint of the study was to determine progression-free survival (PFS). The Full Analysis Set (FAS) comprised 280 patients. Median PFS calculated from enrolment was 270 days in the FAS population. The metastatic involvement of the liver or more than one organ significantly decreased (250 and 245 days), while a clinical response achieved significantly increased (partial response: 404, complete response: 623 days) the mPFS calculated from enrolment. PFS calculated from the start of the first-line treatment was significantly decreased by the presence of mutant RAS gene (481 vs. 395 days). The results confirm the efficacy, known prognostic factors and safety profile of bevacizumab in combination with chemotherapy dosed during standard oncology care in Hungarian centres.

Purpose: The neoadjuvant use of pertuzumab and trastuzumab with chemotherapy improves the pathologic complete response (pCR) in early HER2+ breast cancer. The aim of this study was to determine the pCR rate obtained with dual HER2 blockade in routine clinical practice. The secondary and tertiary objective was to investigate the impact of neoadjuvant systemic therapy (NST) on performing breast-conserving surgery and survival data. Methods: This was a multicentre, retrospective, observational study in patients with stage II and III HER2+ early breast cancer who received pertuzumab and trastuzumab-based NST. Data were collected from patients' medical records. Results: Eighty-two patients were included in the study treated in 8 cancer centers in Hungary between March 2015 and January 2020. The study included women with a median age of 50.3 years. The majority of the patients (95%) received a sequence of anthracycline-based chemotherapy followed by docetaxel. pCR was achieved in 54% of the cases. As a result of NST a significant increase of conservative breast surgeries (33% vs. 3.6% planned, p = 0.0001) was observed. Ki67 expression and neutrophil-to-lymphocyte ratio (NLR) significantly predicted pCR. None of the variables were independent predictors of DFS. Conclusion: The pCR rate achieved in our study demonstrates the reproducibility of trial data in a real-world population. The rate of breast-conserving surgery was significantly increased., Competing Interests: The authors declare that there are no known conflicts of interest associated with this publication and there was no significant financial support for this work that could have influenced its outcome. The authors state that the following financial relationships were not in any respect related to the present study. KB received consulting fees from Pfizer, Novartis, Eli Lilly, and Roche. ZH has received speaker honorarium from Roche, Pfizer, Eli-Lilly, Novartis, AstraZeneca, Amgen, Swixx, Bayer, Sandoz, Merck, Abbvie, Amicus, Egis, TEVA, Boeringer, BMS, Med-Gen Sol, and Oncompass. ZK received consulting fees from AstraZeneca EGIS, Pfizer, Novartis, Eli Lilly, Richter, and Roche. LL received consulting fees from Roche. GR received consulting fees from Pfizer, Novartis, Eli Lilly, and Roche. AR, TC, KM and BB declares no conflict of interest., (Copyright © 2021 Boér, Kahán, Landherr, Csőszi, Máhr, Ruzsa, Horváth, Budai and Rubovszky.)

Considerable evidence supports the rationale for postoperative radiotherapy after breast cancer surgery. Moreover, local tumour control affects survival too. High-dose irradiation is inherently associated with an increased risk of secondary malignancies in the long run. This radiobiological phenomenon raises the question whether it is worth taking this hazard, and the exact level of the risk of a secondary malignancy should be clarified. Answering these questions is important, regarding the large population size of breast cancer survivors, as well as patients' improving survival rates and time. The postoperative radiation load to the ipsilateral lung tissue can be reduced, but it is still significant. The current literature review aims to evaluate the risk of secondary lung cancer associated with breast cancer- specific radiotherapy. Published evidence suggests that the benefits of postoperative radiotherapy following breast cancer surgery are much higher than the minimal risk of secondary lung cancer associated with this management strategy.

The radiotherapy (RT) expert panel revised and updated the RT guidelines accepted in 2016 at the 3rd Hungarian Breast Cancer Consensus Conference based on new scientific evidence. Radiotherapy after breast-conserving surgery (BCS) is indicated in ductal carcinoma in situ (St. 0), as RT decreases the risk of local recurrence (LR) by 50-60%. In early stage (St. I-II) invasive breast cancer RT remains a standard treatment following BCS. However, in elderly (≥70 years) patients with stage I, hormone receptor positive tumour hormonal therapy without RT can be considered. Hypofractionated whole breast irradiation (WBI) and for selected cases accelerated partial breast irradiation are validated treatment alternatives of conventional WBI. Following mastectomy RT significantly decreases the risk of LR and improves overall survival of patients having 1 to 3 or ≥4 positive axillary lymph nodes. In selected cases of patients with 1 to 2 positive sentinel lymph nodes axillary dissection can be substituted with axillary RT. After neoadjuvant chemotherapy (NAC) followed by BCS WBI is mandatory, while after NAC followed by mastectomy locoregional RT should be given in cases of initial stage III-IV and ypN1 axillary status.

At present an estimated hundred millions of women worldwide use oral contraception, but the influence of hormonal contraception on carcinogenesis of breast is not fully understood. Previous studies of breast cancer risk show inconsistent findings - from zero elevation to approximately 30%-40% increase in risk. The beneficial effect on ovarian and endometrial cancer risk is apparent. In this literature review we attempt to determine effects of oral contraception in relation to the risk of breast cancer. The risk increased with longer duration of use, but absolute increase is very small. "Beneficial effects of OCs on the gynecological cancers thus outweighed adverse effects." (Vessey).

Theobroma cacao, the source of cocoa, is a crop of particular importance in many developing countries. Availability of elite planting material is a limiting factor for increasing productivity of Theobroma cacao; therefore, the development of new strategies for clonal propagation is essential to improve farmers' incomes and to meet increasing global demand for cocoa. To develop a more efficient embryogenesis system for cacao, tissue was transformed with a transgene encoding a fusion of Leafy Cotyledon 2 (TcLEC2) to a glucocorticoid receptor domain (GR) to control nuclear localization of the protein. Upon application of the glucocorticoid dexamethasone (dex), downstream targets of LEC2 involved in seed-development were up-regulated and somatic embryos (SEs) were successfully regenerated from TcLEC2-GR transgenic flower and leaf tissue in large numbers. Immature SEs regenerated from TcLEC2-GR leaves were smaller in size than immature SEs from floral tissue, suggesting a different ontogenetic origin. Additionally, exposure of TcLEC2-GR floral explants to dex increased the number of SEs compared to floral explants from control, non-transgenic trees or from TcLEC2-GR floral explants not treated with dex. Testing different durations of exposure to dex indicated that a three-day treatment produced optimal embryo regeneration. Leaf derived SEs were successfully grown to maturity, converted into plants, and established in the greenhouse, demonstrating that these embryos are fully developmentally competent. In summary, we demonstrate that regulating TcLEC2 activity offers a powerful new strategy for optimizing somatic embryogenesis pipelines for cacao., Competing Interests: The authors have the following interests: Andrew S. Fister is employed by Pairwise Plants and Yufan Zhang by Essenlix Corporation. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Importance: Everolimus plus exemestane and capecitabine are approved second-line therapies for advanced breast cancer., Objective: A postapproval commitment to health authorities to estimate the clinical benefit of everolimus plus exemestane vs everolimus or capecitabine monotherapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer., Design: Open-label, randomized, phase 2 trial of treatment effects in postmenopausal women with advanced breast cancer that had progressed during treatment with nonsteroidal aromatase inhibitors., Interventions: Patients were randomized to 3 treatment regimens: (1) everolimus (10 mg/d) plus exemestane (25 mg/d); (2) everolimus alone (10 mg/d); and (3) capecitabine alone (1250 mg/m2 twice daily)., Main Outcomes and Measures: Estimated hazard ratios (HRs) of progression-free survival (PFS) for everolimus plus exemestane vs everolimus alone (primary objective) or capecitabine alone (key secondary objective). Safety was a secondary objective. No formal statistical comparisons were planned., Results: A total of 309 postmenopausal women were enrolled, median age, 61 years (range, 32-88 years). Of these, 104 received everolimus plus exemestane; 103, everolimus alone; and 102, capecitabine alone. Median follow-up from randomization to the analysis cutoff (June 1, 2017) was 37.6 months. Estimated HR of PFS was 0.74 (90% CI, 0.57-0.97) for the primary objective of everolimus plus exemestane vs everolimus alone and 1.26 (90% CI, 0.96-1.66) for everolimus plus exemestane vs capecitabine alone. Between treatment arms, potential informative censoring was noted, and a stratified multivariate Cox regression model was used to account for imbalances in baseline characteristics; a consistent HR was observed for everolimus plus exemestane vs everolimus (0.73; 90% CI, 0.56-0.97), but the HR was closer to 1 for everolimus plus exemestane vs capecitabine (1.15; 90% CI, 0.86-1.52). Grade 3 to 4 adverse events were more frequent with capecitabine (74%; n = 75) vs everolimus plus exemestane (70%; n = 73) or everolimus alone (59%; n = 61). Serious adverse events were more frequent with everolimus plus exemestane (36%; n = 37) vs everolimus alone (29%; n = 30) or capecitabine (29%; n = 30)., Conclusions and Relevance: These findings suggest that everolimus plus exemestane combination therapy offers a PFS benefit vs everolimus alone, and they support continued use of this therapy in this setting. A numerical PFS difference with capecitabine vs everolimus plus exemestane should be interpreted cautiously owing to imbalances among baseline characteristics and potential informative censoring., Trial Registration: ClinicalTrials.gov identifier: NCT01783444.

This randomized, open-label, active-controlled study investigated the safety and efficacy of three doses of Rolontis (eflapegrastim), a novel, long-acting myeloid growth factor, versus pegfilgrastim in breast cancer patients being treated with docetaxel and cyclophosphamide (TC). The primary efficacy endpoint was duration of severe neutropenia (DSN) during the first cycle of treatment. Patients who were candidates for adjuvant/neoadjuvant TC chemotherapy were eligible for participation. TC was administered on Day 1, followed by 45, 135, or 270 μg/kg Rolontis or 6 mg pegfilgrastim on Day 2. Complete blood counts were monitored daily when the absolute neutrophil count (ANC) fell to <1.5 × 10 9 /L. Up to four cycles of TC were investigated. The difference in DSN (time from ANC <0.5 × 10 9 /L to ANC recovery ≥2.0 × 10 9 /L) between the Rolontis and pegfilgrastim groups was -0.28 days (confidence interval [CI]: -0.56, -0.06) at 270 μg/kg, 0.14 days (CI: -0.28, 0.64) at 135 μg/kg, and 0.72 days (CI: 0.19, 1.27) at 45 μg/kg. Noninferiority to pegfilgrastim was demonstrated at 135 μg/kg (P = 0.002) and 270 μg/kg (P < .001), with superiority demonstrated at 270 μg/kg (0.03 days; P = 0.023). The most common treatment-related adverse events (AEs) were bone pain, myalgia, arthralgia, back pain, and elevated white blood cell counts, with similar incidences across groups. All doses of Rolontis were well tolerated, and no new or significant treatment-related toxicities were observed. In Cycle 1, Rolontis demonstrated noninferiority at the 135 μg/kg dose and statistical superiority in DSN at the 270 μg/kg dose when compared to pegfilgrastim., (© 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Regular consumption of alcohol increases the risk of developing (one or more of) several malignant conditions: the frequency of tumours in the aerodigestive tract, in the liver, in the colorectal region and in the breast is increased. The principal carcinogen component of alcoholic drinks is ethanol itself; the effect is unmistakably proportional to the daily/weekly dosage. Under the influence of alcohol-dehydrogenase, ethanol will metabolise to acetaldehyde, which is a known carcinogen. Among other things chronic alcohol consumption promotes the production of endogen hormones, affects the insulin-like growth factor-1, alters several biological pathways, raises oxidative stress, and damages the genes. Even modest daily alcohol intake will increase the risk of breast cancer.

Theobroma cacao , the source of cocoa, suffers significant losses to a variety of pathogens resulting in reduced incomes for millions of farmers in developing countries. Development of disease resistant cacao varieties is an essential strategy to combat this threat, but is limited by sources of genetic resistance and the slow generation time of this tropical tree crop. In this study, we present the first application of genome editing technology in cacao, using Agrobacterium-mediated transient transformation to introduce CRISPR/Cas9 components into cacao leaves and cotyledon cells. As a first proof of concept, we targeted the cacao Non-Expressor of Pathogenesis-Related 3 (TcNPR3) gene, a suppressor of the defense response. After demonstrating activity of designed single-guide RNAs (sgRNA) in vitro , we used Agrobacterium to introduce a CRISPR/Cas9 system into leaf tissue, and identified the presence of deletions in 27% of TcNPR3 copies in the treated tissues. The edited tissue exhibited an increased resistance to infection with the cacao pathogen Phytophthora tropicalis and elevated expression of downstream defense genes. Analysis of off-target mutagenesis in sequences similar to sgRNA target sites using high-throughput sequencing did not reveal mutations above background sequencing error rates. These results confirm the function of NPR3 as a repressor of the cacao immune system and demonstrate the application of CRISPR/Cas9 as a powerful functional genomics tool for cacao. Several stably transformed and genome edited somatic embryos were obtained via Agrobacterium -mediated transformation, and ongoing work will test the effectiveness of this approach at a whole plant level.

With the continually growing number of cancer survivors in the past decades there is an increased interest in understanding and treating the adverse events of cancer therapy, which damage the survivor's quality of life. Post-treatment cognitive impairment (chemobrain) is well known in women with breast cancer and other patients with malignancy. The goal of the current short review is to arouse the caregivers' attention to the not severe, but real problem.

Due to the limited experience with capecitabine plus docetaxel (XT) combination in the first-line treatment of metastatic breast cancer in Hungary, the main objective of the study was to analyze the effectiveness and tolerability of XT therapy. A prospective, open-label, non-randomized, single-arm, multicenter, observational study was designed. All female patients were eligible whose metastatic breast cancer could be treated with the XT protocol according to the summary of product characteristics of the drugs. The median progression free survival was 9.9 ± 3.0 months. Time to treatment failure was 4.6 ± 5.1 months on average. The overall response rate was 28.9 %, the clinical benefit rate was 73.3 %. The treatment was discontinued in 35.6 % of patients due to disease progression and in 20.0 % due to adverse events (AE). 33 patients with a total of 73 AEs have been reported, and 13 of them had serious adverse events (SAE). The efficacy and the safety profile of XT chemotherapy proven in the study are consistent with the results demonstrated in randomized trials. First-line XT chemotherapy effectively improves the PFS in metastatic breast cancer.

Some disseminated tumor cells (as "seeds") feel well in the skeletal tissue, as a "soil", but the humoral crosstalk between tumor cells and bone cells disrupts the normal bone homeostasis (remodeling), which leads to a vicious circle, the multiple bone metastatic disease. The tumor cells could stimulate bone resorption, bone neo-formation or both, characteristic of the primary tumor. This usually incurable condition involves serious consequences, as fractures, pain, surgeries, irradiations, plegias, hypercalcemia, etc. (skeletal-related events, SREs), which destroy the quality of life. Targeting bone resorption with bisphosphonates or RANK ligand dependent mechanism could improve the rate of serious SREs and disease-free survival.

Background: A modest proportion of patients with early stage hormone receptor-positive (HR+), HER2-negative (HER2-) breast cancer benefit from adjuvant chemotherapy. Traditionally, treatment recommendations are based on clinical/pathologic criteria that are not predictive of chemotherapy benefit. Multigene assays provide prognostic and predictive information that can help to make more informed treatment decisions. The MAGIC survey evaluated international differences in treatment recommendations, how traditional parameters are used for making treatment choices, and for which patients treating physicians feel most uncertain about their decisions., Methods: The MAGIC survey captured respondents' demographics, practice patterns, relevance of traditional parameters for treatment decisions, and use of or interest in using multigene assays. Using this information, a predictive model was created to simulate treatment recommendations for 672 patient profiles., Results: The survey was completed by 911 respondents (879 clinicians, 32 pathologists) from 52 countries. Chemo-endocrine therapy was recommended more often than endocrine therapy alone, but there was substantial heterogeneity in treatment recommendations in 52% of the patient profiles; approximately every fourth physician provided a different treatment recommendation. The majority of physicians indicated they wanted to use multigene assays clinically. Lack of reimbursement/availability were the main reasons for non-usage., Conclusions: The survey reveals substantial heterogeneity in treatment recommendations. Physicians have uncertainty in treatment recommendations in a high proportion of patients with intermediate risk features using traditional parameters. In HR+, HER2- patients with early disease the findings highlight the need for additional markers that are both prognostic and predictive of chemotherapy benefit that may support more-informed treatment decisions., (Copyright © 2017. Published by Elsevier Ltd.)

About 50% of all patients with cancer eventually develop anorexia/cachexia syndrome, which represents a complex clinical syndrome occurring in several illnesses, including cancer. The syndrome is characterized by systemic inflammation and primarily loss of body fat and body mass. In this review we shortly summarize the pathomechanism of anorexia/cachexia syndrome and list the current pharmacological approaches.

The radiotherapy expert panel revised and updated the radiotherapy (RT) guidelines accepted in 2009 at the 2nd Hungarian Breast Cancer Consensus Conference based on new scientific evidence. Radiotherapy of the conserved breast is indicated in ductal carcinoma in situ (St. 0), as RT decreases the risk of local recurrence by 60%. In early stage (St. I-II) invasive breast cancer RT remains a standard treatment following breast conserving surgery. However, in elderly (≥70 years) patients with stage I, hormone receptor positive tumour hormonal therapy without RT can be considered. Hypofractionated (15×2.67 Gy) whole breast irradiation and for selected cases accelerated partial breast irradiation are validated treatment alternatives of conventional (25×2 Gy) whole breast irradiation. Following mastectomy RT significantly decreases the risk of locoregional recurrence and improves overall survival of patients having 1 to 3 (pN1a) or ≥4 (pN2a, pN3a) positive axillary lymph nodes. In selected cases of patients with 1 to 2 positive sentinel lymph nodes axillary dissection can be omitted and substituted with axillary RT. After neoadjuvant chemotherapy (NAC) followed by breast conserving surgery whole breast irradiation is mandatory, while after NAC followed by mastectomy locoregional RT should be given in cases of initial stage III-IV and ypN1 axillary status.

Endocrine agents are well established standards of care in hormone-sensitive postmenopausal breast cancer. The pure estrogen receptor antagonist (down-regulator) fulvestrant after binding to the ER induces its conformational change which disrupts ER signal and accelerates ER degradation. Fulvestrant is devoid of partial agonist activity. In unselected patients there was no difference in TTP between "standard dose" fulvestrant and aromatase inhibitors, but in first-line treatment of advanced breast cancer the elevated dose of fulvestrant may delay progression and may extend the overall survival compared with aromatase inhibitors.

The aims of our study were to describe the history and development of intracavitary brachytherapy in the treatment of gynecological tumors, to introduce our current practice for intracavitary brachytherapy treatments based on CT planning. Gynecological intracavitary brachytherapy has been applied in our department since the early 1930s. After a long development it has been completely renewed by 2014. In our center definitive and/or preoperative gynecological HDR-AL brachytherapy treatments were given to 25 patients (13 corpus uterine cancer patients and 12 cervical cancer patients) during the period of 01. 01. 2014-31. 01. 2015. In each case, target volumes were planned by CT images, DVH (dose volume histogram) analysis was performed in order to calculate the radiation tolerance dose of rectum and urinary bladder. Evaluation was performed by the EclipseTM 11.0.47. brachytherapy treatment planning system. During the definitive treatments of the 13 uterine cancer patients the D2cc value related to rectum tolerance was 66.3 GyEQD2 (46-91 Gy). The average D2cc value of urinary bladder tolerance was 76.5 GyEQD2 (30-112 Gy). CI was 0.72 (0.6-0.95). Average value of COIN was 0.57 (0.35-0.78). Compared to the prescribed dose D100 and D90 values were given in ratios. Compared to the volume which receives 100% of reference dose V150 and V200 values were also given in ratios. D100 and D90 were calculated to be 0.66 (0.47-0.97) and 0.91 (0.8-1.25). V150 and V200 volumes were 0.11 (0.04-0.18) and 0.06 (0.02-0.1). During the definitive treatments of 12 cervical cancer patients the D2cc value related to rectum tolerance calculated by DVH was 75.2 GyEQD2 (60-82 Gy). The average D2cc value of urinary bladder tolerance was 85 GyEQD2 based on DVH. CI was 0.66 (0.42-0.76). Average value of COIN was 0.52 (0.32-0.78). Mean value of DHI was 0.46 (0.27-0.54). D100 and D90 were calculated to be 0.72 (0.57-0.89) and 0.91 (0.84-1.11). V150 and V200 volumes were 0.057 (0.02-0.13) and 0.02 (0.002-0.06). During treatments no severe side effects were found. During gynecological intracavitary HDR therapies the calculated dose of the target volume can be given safely using the EclipseTM 11.0.47. brachytherapy planning system and CT-based planning. CT-based treatment planning provides optimal safety for organs at risk, acceptable doses for rectum and urinary bladder while the target volume receives the proper prescribed dose.

The origin of novel traits is recognized as an important process underlying many major evolutionary radiations. We studied the genetic basis for the evolution of haustoria, the novel feeding organs of parasitic flowering plants, using comparative transcriptome sequencing in three species of Orobanchaceae. Around 180 genes are upregulated during haustorial development following host attachment in at least two species, and these are enriched in proteases, cell wall modifying enzymes, and extracellular secretion proteins. Additionally, about 100 shared genes are upregulated in response to haustorium inducing factors prior to host attachment. Collectively, we refer to these newly identified genes as putative "parasitism genes." Most of these parasitism genes are derived from gene duplications in a common ancestor of Orobanchaceae and Mimulus guttatus, a related nonparasitic plant. Additionally, the signature of relaxed purifying selection and/or adaptive evolution at specific sites was detected in many haustorial genes, and may play an important role in parasite evolution. Comparative analysis of gene expression patterns in parasitic and nonparasitic angiosperms suggests that parasitism genes are derived primarily from root and floral tissues, but with some genes co-opted from other tissues. Gene duplication, often taking place in a nonparasitic ancestor of Orobanchaceae, followed by regulatory neofunctionalization, was an important process in the origin of parasitic haustoria., (© The Author 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.)

Background: Patients with metastatic colorectal cancer receive chemotherapy prior liver resection more and more frequently. Histopathologic assessment methods of the resected specimen could evaluate the response to chemotherapy. In this study it is analyzed if these histopathologic changes are specific to preoperative chemotherapy and if these methods have correlation with survival., Methods: Sixty three patients with available pathology slides, resected for colorectal cancer liver metastases were enrolled in this study. 46 patients (73%) received neoadjuvant chemotherapy. Five pathological evaluation methods were compared according to the literature: [1] residual tumor cell ratio, [2] tumor regression grade (TRG) scoring system, [3] modified tumor regression grade (mTRG) scoring system with the type of necrosis, [4] pattern of tumor regression and [5] the tumor thickness at the tumor-normal interface (TNI)., Results: Analyzing the pathological methods between the chemotherapy (CTX) and the non-chemotherapy group (NC), we found that that four evaluation methods showed significant and one showed strong correlation with the use of chemotherapy. (Residual tumor cell ratio: p = 0.08; TRG: p <0.01; mTRG: p = 0.03; pattern of tumor regression: p <0.01; TNI: p = 0.02). In the chemotherapy group none of the analyzed pathological methods showed significant correlation with progression free survival (PFS) or with overall survival (OS). Residual tumor cell ratio, TRG and the pattern of tumor cells showed positive but not significant correlation with OS and PFS and a slight difference in the group of patients with TNI <2 mm could be documented., Conclusions: Tumor regression grade (TRG) and tumor thickness at the tumor-normal interface (TNI) were the most useful methods for pathological response evaluation and these methods had some correlation with survival. According to these data, authors concluded, that a reproducible and well defined scoring system, based on different histopathological evaluation methods should be developed to predict more accurately the effect of neoadjuvant chemotherapy in CRCLM patients.

The active form of vitamin D, in conjunction with his own receptor, affect a multitude of biological processes in the cell (inter alia it influences the expression of oncogenes and tumor suppressor genes). There is an increasing volume of scientific publications examining the relationships between serum vitamin D levels, vitamin D supplementation and malignant diseases. Some articles suggest inverse relationship between the low serum levels of vitamin D and the breast cancer risk and mortality, whilst other publications do not support this view. Thus the present opinion is conflicted. Vitamin D can exert a beneficial influence on the symptoms and outcomes of a large number of ailments, but its role in affecting cancer is still not completely clear.

Cardiac complications may present a particular problem following radiation treatment applied to the mediastinum and thoracic wall (and especially to the left breast). Exposure of the heart during radiotherapy increases the risk of ischemic heart disease occurring generally years after the treatment. The incidence of radiation cardiotoxicity depends on various factors related to oncological therapies and the patient (details of radiotherapy, age, gender, comorbidities, smoking habits, etc.). Until recently the majority of clinical studies reported increased cardiac morbidity in patients receiving radiation treatment of the chest wall and the breast. Due to modern methods, however, postoperative chest wall and left breast irradiation is much safer today than previously. In order to avoid cardiotoxicity, adherence to clinical practice guidelines for chemo- and targeted therapy of breast cancer, use of the most advanced irradiation procedures, regular monitoring of patients, and close cooperation between cardiologists and oncologists are all recommended.

Background: First-line bevacizumab-paclitaxel therapy demonstrated a median progression-free survival (PFS) of 11 months in three randomized phase III trials on metastatic breast cancer (mBC) (E2100, TURANDOT and CALGB 40502). We assessed the efficacy and safety of bevacizumab-paclitaxel in a routine oncology practice study., Patients and Methods: Patients with previously untreated mBC received bevacizumab-paclitaxel according to the approved indication in Hungary. The primary end-point was PFS. Secondary end-points included time-to-treatment discontinuation, 1-year survival rate, PFS in patients with triple-negative breast cancer (TNBC) and safety., Results: Median PFS in the 220 treated patients was 9.3 (95%CI 7.8-10.8) months. The 1-year survival rate was 68%. In patients with TNBC (N=106), median PFS was 8.3 months (95%CI 7.8-8.8). Adverse events were consistent with the established safety profile of bevacizumab-paclitaxel., Conclusion: Bevacizumab-paclitaxel is an active and well-tolerated first-line treatment for mBC, with notable activity in TNBC.

The skeleton is the most common site to be affected by advanced breast, prostatic, lung, kidney, thyroid and other solid tumors (in addition to myeloma multiplex). Bone metastases cause significant morbidity with nearly always fatal outcome. Over 600 000 new patients diagnosed in the developed countries yearly. On average every 4-6 months patients suffer from series of severe skeletal complications such as pathologic fractures, spinal cord compression, hypercalcemic events, etc., besides the permanent pain. Local external beam radiotherapy, systemic radioisotope-, endocrine-, and chemotherapy, oral and i.v. bisphosphonates and recently s.c. denosumab are the mainstays of treatment, in addition to pain-killers and other usual "classical" interventions. The modern treatments singificantly reduce the probability of skeletal complications and improve the patients' quality of life and, sometimes, they extend the survival as well. The authors briefly summarize the available treatment options.

Background: Previous studies in basal angiosperms have provided insight into the diversity within the angiosperm lineage and helped to polarize analyses of flowering plant evolution. However, there is still not an experimental system for genetic studies among basal angiosperms to facilitate comparative studies and functional investigation. It would be desirable to identify a basal angiosperm experimental system that possesses many of the features found in existing plant model systems (e.g., Arabidopsis and Oryza)., Results: We have considered all basal angiosperm families for general characteristics important for experimental systems, including availability to the scientific community, growth habit, and membership in a large basal angiosperm group that displays a wide spectrum of phenotypic diversity. Most basal angiosperms are woody or aquatic, thus are not well-suited for large scale cultivation, and were excluded. We further investigated members of Aristolochiaceae for ease of culture, life cycle, genome size, and chromosome number. We demonstrated self-compatibility for Aristolochia elegans and A. fimbriata, and transformation with a GFP reporter construct for Saruma henryi and A. fimbriata. Furthermore, A. fimbriata was easily cultivated with a life cycle of just three months, could be regenerated in a tissue culture system, and had one of the smallest genomes among basal angiosperms. An extensive multi-tissue EST dataset was produced for A. fimbriata that includes over 3.8 million 454 sequence reads., Conclusions: Aristolochia fimbriata has numerous features that facilitate genetic studies and is suggested as a potential model system for use with a wide variety of technologies. Emerging genetic and genomic tools for A. fimbriata and closely related species can aid the investigation of floral biology, developmental genetics, biochemical pathways important in plant-insect interactions as well as human health, and various other features present in early angiosperms.

Nowadays PET/CT examinations have got more and more important role during cancer treatment. It has importance not only in diagnostic examination and staging but also in the radiation planning process and measuring the therapeutic effect. From November 2006 to November 2010 there were 153 PET/CT examinations requested by the Oncology Outpatient Clinic, Uzsoki Hospital. Nine patients were excluded from the examination. In the clinical trial we have aimed to measure what the correlation between the oncologists' questions and the PET/CT results was, in how many cases the PET/CT had influence on therapeutic decision-making. In the case of the patients waiting for the operation we compared the results of the pathological examinations to the results of the PET/CT. The oncologists got the expected answers in 79 cases, while in 45 cases the answers were negative. In 10 cases there were no definite answers. Ten cases proved to be false negative or false positive based on the later pathological examination. As a result of the PET/CT findings the originally planned therapeutic decisions or the therapies in process have been modified in 77 cases. To sum up, the PET/CT gave the expected answers to the oncologists' questions in more than half of the cases (54.9%) and modified the originally prescribed therapy in 53.5% of the cases.

Parasitism in flowering plants has evolved at least 11 times [1]. Only one family, Orobanchaceae, comprises all major nutritional types of parasites: facultative, hemiparasitic (partially photosynthetic), and holoparasitic (nonphotosynthetic) [2]. Additionally, the family includes Lindenbergia, a nonparasitic genus sister to all parasitic Orobanchaceae [3-6]. Parasitic Orobanchaceae include species with severe economic impacts: Striga (witchweed), for example, affects over 50 million hectares of crops in sub-Saharan Africa, causing more than $3 billion in damage annually [7]. Although gene losses and increased substitution rates have been characterized for parasitic plant plastid genomes [5, 8-11], the nuclear genome and transcriptome remain largely unexplored. The Parasitic Plant Genome Project (PPGP; http://ppgp.huck.psu.edu/) [2] is leveraging the natural variation in Orobanchaceae to explore the evolution and genomic consequences of parasitism in plants through a massive transcriptome and gene discovery project involving Triphysaria versicolor (facultative hemiparasite), Striga hermonthica (obligate hemiparasite), and Phelipanche aegyptiaca (Orobanche [12]; holoparasite). Here we present the first set of large-scale genomic resources for parasitic plant comparative biology. Transcriptomes of above-ground tissues reveal that, in addition to the predictable loss of photosynthesis-related gene expression in P. aegyptiaca, the nonphotosynthetic parasite retains an intact, expressed, and selectively constrained chlorophyll synthesis pathway., (Copyright © 2011 Elsevier Ltd. All rights reserved.)