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Biomedical subjects

Michael Baum

Publications and source records attributed to Michael Baum.

At least 19 recordsLinked to original sources

On the origin of the late-flowering ppd-H1 allele in barley.

To breed for climate resilient crops, an understanding of the genetic and environmental factors influencing adaptation is critical. Barley provides a model species to study adaptation to climate change. Here we present a detailed analysis of genetic variation at a major photoperiod response locus and relate this to the domestication history and dispersal of barley. The PPD-H1 locus (a PSEUDO-RESPONSE REGULATOR 7) promotes flowering under long-day conditions, and a natural mutation at this locus resulted in a recessive, late-flowering ppd-H1 allele. This mutation proved beneficial in high-latitude environments such as Northern Europe, where it allows extended vegetative growth during long spring days. We infer the origin of the mutated late-flowering ppd-H1 allele by re-sequencing a large geo-referenced collection of 942 Hordeum spontaneum, 5 Hordeum agriocrithon and 1110 domesticated (Hordeum vulgare) barleys. We demonstrate that the late-flowering phenotype originated from Desert-type wild barley in the Southern Levant and present evidence suggesting a post-domestication origin of the mutated ppd-H1 allele.

Hordeum↗

Targeted intraoperative radiotherapy (TARGIT) yields very low recurrence rates when given as a boost.

PURPOSE: Patients undergoing breast-conserving surgery were offered boost radiotherapy with targeted intraoperative radiotherapy (TARGIT) using the Intrabeam system to test the feasibility, safety, and efficacy of the new approach. METHODS AND MATERIALS: We treated 302 cancers in 301 unselected patients. This was not a low-risk group. One-third of patients (98/301) were younger than 51 years of age. More than half of the tumors (172, 57%) were between 1 cm and 2 cm, and one-fifth (62, 21%) were >2 cm; 29% (86) had a Grade 3 tumor and, in 29% (87), axillary lymph nodes contained metastasis. After primary surgery, 20 Gy was delivered intraoperatively to the surface of the tumor bed, followed by external-beam radiotherapy (EBRT), but excluding the usual boost. RESULTS: The treatment was well tolerated. The follow-up ranged from 3 to 80 months (164 and 90 patients completed 2 and 3 years follow-up, respectively). Four patients (1.3%) had local recurrence. The Kaplan-Meier estimate of local recurrence is 2.6% (SE = 1.7) at 5 years. This compares favorably with the 4.3% recurrence rate in boosted patients from the EORTC boost study, in which only 8.1% patients were node-positive, as opposed to 29% in our series. CONCLUSION: Targeted intraoperative radiotherapy combined with EBRT results in a low local recurrence rate. This could be attributed to both accurate targeting and timeliness of the treatment. These data support the need for a randomized trial to test whether the TARGIT boost is superior to conventional external boost, especially in high-risk women.

Adult↗

Transcriptional analysis between two wheat near-isogenic lines contrasting in aluminum tolerance under aluminum stress.

To understand the mechanisms of aluminum (Al) tolerance in wheat (Triticum aestivum L.), suppression subtractive hybridization (SSH) libraries were constructed from Al-stressed roots of two near-isogenic lines (NILs). A total of 1,065 putative genes from the SSH libraries was printed in a cDNA array. Relative expression levels of those genes were compared between two NILs at seven time points of Al stress from 15 min to 7 days. Fifty-seven genes were differentially expressed for at least one time point of Al treatment. Among them, 28 genes including genes for aluminum-activated malate transporter-1, ent-kaurenoic acid oxidase-1, beta-glucosidase, lectin, histidine kinase, and phospoenolpyruvate carboxylase showed more abundant transcripts in Chisholm-T and therefore may facilitate Al tolerance. In addition, a set of genes related to senescence and starvation of nitrogen, iron, and sulfur, such as copper chaperone homolog, nitrogen regulatory gene-2, yellow stripe-1, and methylthioribose kinase, was highly expressed in Chisholm-S under Al stress. The results suggest that Al tolerance may be co-regulated by multiple genes with diverse functions, and those genes abundantly expressed in Chisholm-T may play important roles in enhancing Al tolerance. The down-regulated genes in Chisholm-S may repress root growth and restrict uptake of essential nutrient elements, and lead to root senescence.

Aluminum↗

The role of complementary and alternative medicine in the management of early breast cancer: recommendations of the European Society of Mastology (EUSOMA).

Patients diagnosed with breast cancer have many needs that for a start include the expectation of cure. Where cure is unlikely there is always a place for hope and spiritual support. Furthermore whether dealing with the early stages or with the advanced disease patients require symptomatic control that encompasses pain relief, control of nausea and vomiting and psychological distress. To achieve all of these goals there is a need that goes beyond the role of scientific medicine. This position papers describes the guidelines for the use of complimentary and alternative medicine (CAM) developed by a workshop on behalf of the European Society of Mastology (EUSOMA).

Breast Neoplasms↗

Role of complementary and alternative medicine in the care of patients with breast cancer: report of the European Society of Mastology (EUSOMA) Workshop, Florence, Italy, December 2004.

The aim of the European Society of Mastology (EUSOMA) Workshop, Florence, Italy, December 2004, was to produce guidelines on the use of complementary and alternative medicine (CAM) for breast cancer. The widespread use of CAM has to be acknowledged and the reasons for this understood. Deficiencies in the practice of conventional medicine that lead to the adoption of CAM need to be addressed. At the same time, CAM use for breast cancer should be quality controlled, avoiding double standards in evaluation, whilst recognising the problems of CAM research. These guidelines, which appear in an accompanying paper, aim to help oncologists and cancer patients alike.

Breast Neoplasms↗

Retrospective analysis of time to recurrence in the ATAC trial according to hormone receptor status: an hypothesis-generating study.

PURPOSE: Arimidex, tamoxifen alone, or in combination (ATAC) trial of anastrozole (Arimidex) versus tamoxifen or a combination of the two in 9,366 postmenopausal patients with primary breast cancer found a significant improvement in disease-free survival and time to recurrence (TTR) for anastrozole compared with tamoxifen, that was restricted to patients with hormone receptor-positive (ie, estrogen receptor-positive [ER+] and/or progesterone receptor-positive [PgR+]) disease, the target population for these therapies. We retrospectively tested the hypothesis that this benefit might differ according to PgR status. PATIENTS AND METHODS: TTR was compared between the three treatment groups for subgroups defined by ER and PgR status using Cox's proportional hazards model, with and without adjustment for baseline variables. RESULTS: The unadjusted hazard ratio (HR) for anastrozole versus tamoxifen for TTR was 0.74 (95% CI, 0.64 to 0.87) for women with either ER+ or PgR+ tumors. In the ER+/PgR+ subgroup (n = 3,834) the HR was 0.84 (95% CI, 0.69 to 1.02) compared with 0.43 (95% CI, 0.31 to 0.61) in the ER+/PgR-negative (PgR-) subgroup (n = 880). In the adjusted model the HRs were 0.83 and 0.45, respectively. CONCLUSION: Time to recurrence was longer for anastrozole- than tamoxifen-treated patients in both ER+/PgR+ and ER+/PgR- subgroups, but the benefit was substantially greater in the PgR- subgroup. As this was an "exploratory" analysis, this effect should be considered as hypothesis generating and assessed prospectively in other trials comparing the adjuvant use of an aromatase inhibitor with tamoxifen.

Anastrozole↗

Does surgery unfavourably perturb the "natural history" of early breast cancer by accelerating the appearance of distant metastases?

This historical perspective on breast cancer tells us how and why certain therapeutic eras have reached ascendancy and then declined. Therapeutic revolutions occur after a crisis develops when there is a general recognition that clinical interventions are not producing positive results predicted by the prevailing paradigm. The attitude of pre-modern surgeons was influenced by the very real possibility of doing more harm than good by operating upon women with breast cancer. Up until Halsted, the general consensus was clearly that, unless forced by the circumstances, surgical resection should be avoided for disease much more advanced than very early stage tumours (the cacoethesis of Celsus). Twentieth century progress in antisepsis, anaesthesia, and surgery changed this point of view. The first three quarters of that century saw more and more aggressive operations performed while the last quarter century reversed this trend, with reduction of the size of breast cancer operations based largely on the teachings of Fisher. A new crisis is upon us now in that trials of early detection have resulted in unexpected disadvantages to certain subgroups and there is previously unreported structure in early hazard of relapse, clinical data that suggests the act of surgery might accelerate the appearance of distant metastases. The explanation we propose that agrees with these results, as well as physicians of antiquity, is that surgery can induce angiogenesis and proliferation of distant dormant micrometastases, especially in young patients with positive nodes.

Breast Neoplasms↗

A survey of breast cancer awareness and knowledge in a Western population: lots of light but little illumination.

There are conflicting data on breast cancer awareness and knowledge in specific population groups. We assessed awareness and knowledge of breast cancer in the general Irish population to identify sources of information on breast cancer and determine factors associated with knowledge and awareness of the disease. Participants (n=2355, 53% female) completed a multi-part questionnaire. Most (81%) had seen or heard something about breast cancer in the recent past and knowledge of symptoms and treatment was good overall. However, 66% of females overestimated their risk of developing disease, 88% underestimated the age at which it was most likely to develop and 56% underestimated 5-year survival. Knowledge of incidence and survival was higher in males (Odds Ratio (OR) 1.3, 95% Confidence Interval (CI); 1.1-1.5), participants with higher education (1.5; 1.2-1.7) and those who received information from television (1.3; 1.1-1.5). Ignorance regarding incidence, outcome and risk makes it unlikely that the general public or at risk females could currently make informed decisions on a range of breast cancer issues.

Adult↗

TARGeted Intraoperative radiotherapy (TARGIT): an innovative approach to partial-breast irradiation.

A revolution is challenging the dogma that local treatment for all patients with breast cancer treated with breast conservation therapy must include postoperative radiotherapy delivered to the whole breast. Such prolonged postoperative radiotherapy is a burden to patients and hospitals and forces many women to chose mastectomy instead. Furthermore, for patients receiving chemotherapy, the start of conventional radiotherapy may be delayed so long as to increase the risk of local relapse. These problems might be eliminated if effective radiotherapy could be given as a single treatment intraoperatively, immediately after the surgery. Local recurrence after breast-conserving surgery usually occurs in the portion of the breast in the immediate proximity of the tumor, even when radiotherapy is omitted. Therefore, it should usually be possible to restrict radiotherapy to only the area adjacent to the tumor in selected women. Based on this premise, we have devised a new technique of partial breast irradiation, with the intention of completing all local treatment in a single session. In this article, we elaborate on the rationale and on the different methods of delivering intraoperative radiotherapy. If this approach is validated in ongoing randomized trials, it could save time, money, and breasts.

Breast Neoplasms↗

Alternative splicing microarrays reveal functional expression of neuron-specific regulators in Hodgkin lymphoma cells.

Alternative splicing provides a versatile mechanism of gene regulation, which is often subverted in disease. We have used customized oligonucleotide microarrays to interrogate simultaneously the levels of expression of splicing factors and the patterns of alternative splicing of genes involved in tumor progression. Analysis of RNAs isolated from cell lines derived from Hodgkin lymphoma tumors indicate that the relative abundance of alternatively spliced isoforms correlates with transformation and tumor grade. Changes in expression of regulators were also detected, and a subset sample was confirmed at the protein level. Ectopic expression of neuron-specific splicing regulatory proteins of the Nova family was observed in some cell lines and tumor samples, correlating with expression of a neuron-specific mRNA isoform of JNK2 kinase. This microarray design can help assess the role of alternative splicing in a variety of biological and medical problems and potentially serve as a diagnostic tool.

Alternative Splicing↗