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1.
Breast Cancer Res Treat ; 184(1): 45-52, 2020 Nov.
Article in English | MEDLINE | ID: mdl-32737713

ABSTRACT

BACKGROUND: Despite the current recommendation for influenza vaccination in cancer patients with active oncological therapy, limited data are available on the efficacy of vaccination in cancer patients receiving targeted therapies. We aimed to investigate the immunogenicity and tolerability of influenza vaccination in breast cancer patients treated with trastuzumab in adjuvant setting. METHODS: A prospective open-label multicenter study was performed including patients with breast cancer during trastuzumab treatment in adjuvant setting and healthy controls. Blood samples were taken before, 4 weeks after, and 12 weeks after a single dose of trivalent influenza vaccine containing inactivated A/California/7/2009 (H1N1) pdm09, A/Hongkong4801/2014 (H3N2), and B/Brisbane/60/2008. Levels of serum antibody titers to hemagglutinin for H1N1 and influenza B strains were measured. RESULTS: Twenty breast cancer patients and 37 controls were included in the study. No difference in seroprotection rate between trastuzumab-treated patients and controls was observed for either H1N1 (100% in both groups) or B strain (78.9% vs. 89.2%, p value = 0.423). A statistically significant increase in geometric mean titers from baseline was seen in both groups and was evident both 4 weeks and 12 weeks after vaccination. Adverse events in the trastuzumab-treated group were uncommon and mild with only one serious adverse event not related to vaccination. CONCLUSION: Breast cancer patients treated with trastuzumab in adjuvant setting seem to benefit from influenza vaccination in terms of immunogenicity without increasing the risk for adverse events. The current data support the recommendation to offer influenza vaccination in breast cancer patients treated with this type of targeted therapy.


Subject(s)
Breast Neoplasms , Influenza A Virus, H1N1 Subtype , Influenza Vaccines , Influenza, Human , Antibodies, Viral , Breast Neoplasms/drug therapy , Female , Hemagglutination Inhibition Tests , Humans , Influenza A Virus, H3N2 Subtype , Influenza Vaccines/adverse effects , Influenza, Human/prevention & control , Prospective Studies , Trastuzumab/adverse effects , Vaccination
2.
BMC Cancer ; 20(1): 1197, 2020 Dec 07.
Article in English | MEDLINE | ID: mdl-33287744

ABSTRACT

BACKGROUND: The incidence of cutaneous malignant melanoma (CMM) is increasing worldwide. In Sweden, over 4600 cases were diagnosed in 2018. The prognosis after radical surgery varies considerably with tumor stage. In recent years, new treatment options have become available for metastatic CMM. Early onset of treatment seems to improve outcome, which suggests that early detection of recurrent disease should be beneficial. Consequently, in several countries imaging is a part of the routine follow-up program after surgery of high risk CMM. However, imaging has drawbacks, including resources required (costs, personnel, equipment) and the radiation exposure. Furthermore, many patients experience anxiety in waiting for the imaging results and investigations of irrelevant findings is another factor that also could cause worry and lead to decreased quality of life. Hence, the impact of imaging in this setting is important to address and no randomized study has previously been conducted. The Swedish national guidelines stipulate follow-up for 3 years by clinical examinations only. METHODS: The TRIM study is a prospective randomized multicenter trial evaluating the potential benefit of imaging and blood tests during follow-up after radical surgery for high-risk CMM, compared to clinical examinations only. Primary endpoint is overall survival (OS) at 5 years. Secondary endpoints are survival from diagnosis of relapse and health-related quality of life (HRQoL). Eligible for inclusion are patients radically operated for CMM stage IIB-C or III with sufficient renal function for iv contrast-enhanced CT and who are expected to be fit for treatment in case of recurrence. The planned number of patients is > 1300. Patients are randomized to clinical examinations for 3 years +/- whole-body imaging with CT or FDG-PET/CT and laboratory tests including S100B protein and LDH. This academic study is supported by the Swedish Melanoma Study Group. DISCUSSION: This is the first randomized prospective trial on the potential benefit of imaging as a part of the follow-up scheme after radical surgery for high-risk CMM. RESULTS: The first patient was recruited in June 2017 and as of April 2020, almost 500 patients had been included at 19 centers in Sweden. TRIAL REGISTRATION: ClinicalTrials.gov , NCT03116412 . Registered 17 April 2017, https://clinicaltrials.gov/ct2/show/study/NCT03116412.


Subject(s)
Melanoma/diagnostic imaging , Skin Neoplasms/diagnostic imaging , Disease-Free Survival , Female , Follow-Up Studies , Humans , Incidence , Male , Melanoma/surgery , Neoplasm Staging , Prognosis , Prospective Studies , Skin Neoplasms/surgery , Melanoma, Cutaneous Malignant
3.
Glob Chang Biol ; 25(2): 589-601, 2019 02.
Article in English | MEDLINE | ID: mdl-30537359

ABSTRACT

Current climate models and observations indicate that atmospheric circulation is being affected by global climate change. To assess how these changes may affect nocturnally migrating bird populations, we need to determine how current patterns of wind assistance at migration altitudes will be enhanced or reduced under future atmospheric conditions. Here, we use information compiled from 143 weather surveillance radars stations within the contiguous United States to estimate the daily altitude, density, and direction of nocturnal migration during the spring and autumn. We intersected this information with wind projections to estimate how wind assistance is expected to change during this century at current migration altitudes. The prevailing westerlies at midlatitudes are projected to increase in strength during spring migration and decrease in strength to a lesser degree during autumn migration. Southerly winds will increase in strength across the continent during both spring and autumn migration, with the strongest gains occurring in the center of the continent. Wind assistance is projected to increase across the central (0.44 m/s; 10.1%) and eastern portions of the continent (0.32 m/s; 9.6%) during spring migration, and wind assistance is projected to decrease within the central (0.32 m/s; 19.3%) and eastern portions of the continent (0.17 m/s; 6.6%) during autumn migration. Thus, across a broad portion of the continent where migration intensity is greatest, the efficiency of nocturnal migration is projected to increase in the spring and decrease in the autumn, potentially affecting time and energy expenditures for many migratory bird species. These findings highlight the importance of placing climate change projections within a relevant ecological context informed through empirical observations, and the need to consider the possibility that climate change may generate both positive and negative implications for natural systems.


Subject(s)
Animal Migration , Birds/physiology , Climate Change , Wind , Animals , Seasons , United States
4.
Biol Lett ; 15(9): 20190383, 2019 09 27.
Article in English | MEDLINE | ID: mdl-31530114

ABSTRACT

Applications of remote sensing data to monitor bird migration usher a new understanding of magnitude and extent of movements across entire flyways. Millions of birds move through the western USA, yet this region is understudied as a migratory corridor. Characterizing movements in the Pacific Flyway offers a unique opportunity to study complementary patterns to those recently highlighted in the Atlantic and Central Flyways. We use weather surveillance radar data from spring and autumn (1995-2018) to examine migrants' behaviours in relation to winds in the Pacific Flyway. Overall, spring migrants tended to drift on winds, but less so at northern latitudes and farther inland from the Pacific coastline. Relationships between winds and autumn flight behaviours were less striking, with no latitudinal or coastal dependencies. Differences in the preferred direction of movement (PDM) and wind direction predicted drift patterns during spring and autumn, with increased drift when wind direction and PDM differences were high. We also observed greater total flight activity through the Pacific Flyway during the spring when compared with the autumn. Such complex relationships among birds' flight strategies, winds and seasonality highlight the variation within a migration system. Characterizations at these scales complement our understanding of strategies to clarify aerial animal movements.


Subject(s)
Animal Migration , Wind , Animals , Birds , Flight, Animal , Radar , Seasons
5.
Cancer ; 124(14): 2923-2930, 2018 07 15.
Article in English | MEDLINE | ID: mdl-29723396

ABSTRACT

BACKGROUND: Several studies have reported a high risk of local disease recurrence (LR) and locoregional disease recurrence (LRR) in patients with breast cancer after neoadjuvant chemotherapy (NCT) and breast-conserving therapy (BCT). The objective of the current study was to identify potential risk factors for LR and LRR after NCT and BCT. METHODS: Individual patient data sets from 9 studies were pooled. The outcomes of interest were the occurrence of LR and/or LRR. A 1-stage meta-analytic approach was used. Cox proportional hazards regression models were applied to identify factors that were predictive of LR and LRR, respectively. RESULTS: A total of 9 studies (4125 patients) provided their data sets. The 10-year LR rate was 6.5%, whereas the 10-year LRR rate was 10.3%. Four factors were found to be associated with a higher risk of LR: 1) estrogen receptor-negative disease; 2) cN + disease; 3) a lack of pathologic complete response in axilla (pN0); and 4) pN2 to pN3 disease. The predictive score for LR determined 3 risk groups: a low-risk, intermediate-risk, and high-risk group with 10-year LR rates of 4.0%, 7.9%, and 20.4%, respectively. Two additional factors were found to be associated with an increased risk of LRR: cT3 to cT4 disease and a lack of pathologic complete response in the breast. The predictive score for LRR determined 3 risk groups; a low-risk, intermediate-risk, and high-risk group with 10-year LRR rates of 3.2%, 10.1%, and 24.1%, respectively. CONCLUSIONS: BCT after NCT appears to be an oncologically safe procedure for a large percentage of patients with breast cancer. Two easy-to-use clinical scores were developed that can help clinicians to identify patients at higher risk of LR and LRR after NCT and BCT and individualize the postoperative treatment plan and follow-up. Cancer 2018;124:2923-30. © 2018 American Cancer Society.


Subject(s)
Breast Neoplasms/therapy , Mastectomy, Segmental , Neoplasm Recurrence, Local/epidemiology , Antineoplastic Combined Chemotherapy Protocols , Axilla , Breast/pathology , Breast/surgery , Breast Neoplasms/pathology , Female , Humans , Incidence , Lymphatic Metastasis/pathology , Neoadjuvant Therapy/methods , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/prevention & control , Neoplasm Staging , Receptors, Estrogen/metabolism , Risk Factors , Sentinel Lymph Node/pathology , Treatment Outcome
6.
Biol Lett ; 14(11)2018 11 14.
Article in English | MEDLINE | ID: mdl-30429244

ABSTRACT

Light cues elicit strong responses from nearly all forms of life, perhaps most notably as circadian rhythms entrained by periods of daylight and darkness. Atypical periods of darkness, like solar eclipses, provide rare opportunities to study biological responses to light cues. By using a continental scale radar network, we investigated responses of flying animals to the total solar eclipse of 21 August 2017. We quantified the number of biological targets in the atmosphere at 143 weather radar stations across the continental United States to investigate whether the decrease in light and temperature at an atypical time would initiate a response like that observed at sunset, when activity in the atmosphere usually increases. Overall, biological activity decreased in the period leading to totality, followed by a short low-altitude spike of biological activity during totality in some radars. This pattern suggests that cues associated with the eclipse were insufficient to initiate nocturnal activity comparable to that occurring at sunset but sufficient to suppress diurnal activity.


Subject(s)
Birds/physiology , Chiroptera/physiology , Darkness , Flight, Animal , Insecta/physiology , Sunlight , Animals , Circadian Rhythm , Temperature , Time Factors , United States
7.
Surg Endosc ; 31(5): 2131-2139, 2017 05.
Article in English | MEDLINE | ID: mdl-27770252

ABSTRACT

BACKGROUND: Inexperienced operating assistants are often tasked with the important role of handling camera navigation during laparoscopic surgery. Incorrect handling can lead to poor visualization, increased operating time, and frustration for the operating surgeon-all of which can compromise patient safety. The objectives of this trial were to examine how to train laparoscopic camera navigation and to explore the transfer of skills to the operating room. MATERIALS AND METHODS: A randomized, single-center superiority trial with three groups: The first group practiced simulation-based camera navigation tasks (camera group), the second group practiced performing a simulation-based cholecystectomy (procedure group), and the third group received no training (control group). Participants were surgical novices without prior laparoscopic experience. The primary outcome was assessment of camera navigation skills during a laparoscopic cholecystectomy. The secondary outcome was technical skills after training, using a previously developed model for testing camera navigational skills. The exploratory outcome measured participants' motivation toward the task as an operating assistant. RESULTS: Thirty-six participants were randomized. No significant difference was found in the primary outcome between the three groups (p = 0.279). The secondary outcome showed no significant difference between the interventions groups, total time 167 s (95% CI, 118-217) and 194 s (95% CI, 152-236) for the camera group and the procedure group, respectively (p = 0.369). Both interventions groups were significantly faster than the control group, 307 s (95% CI, 202-412), p = 0.018 and p = 0.045, respectively. On the exploratory outcome, the control group for two dimensions, interest/enjoyment (p = 0.030) and perceived choice (p = 0.033), had a higher score. CONCLUSIONS: Simulation-based training improves the technical skills required for camera navigation, regardless of practicing camera navigation or the procedure itself. Transfer to the clinical setting could, however, not be demonstrated. The control group demonstrated higher interest/enjoyment and perceived choice than the camera group.


Subject(s)
Cholecystectomy, Laparoscopic/education , Laparoscopy/education , Simulation Training , Virtual Reality , Adult , Female , Humans , Students, Medical , Young Adult
8.
J Anim Ecol ; 85(1): 115-24, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26147535

ABSTRACT

Animals that use flight as their mode of transportation must cope with the fact that their migration and orientation performance is strongly affected by the flow of the medium they are moving in, that is by the winds. Different strategies can be used to mitigate the negative effects and benefit from the positive effects of a moving flow. The strategies an animal can use will be constrained by the relationship between the speed of the flow and the speed of the animal's own propulsion in relation to the surrounding air. Here we analyse entomological and ornithological radar data from north-western Europe to investigate how two different nocturnal migrant taxa, the noctuid moth Autographa gamma and songbirds, deal with wind by analysing variation in resulting flight directions in relation to the wind-dependent angle between the animal's heading and track direction. Our results, from fixed locations along the migratory journey, reveal different global strategies used by moths and songbirds during their migratory journeys. As expected, nocturnally migrating moths experienced a greater degree of wind drift than nocturnally migrating songbirds, but both groups were more affected by wind in autumn than in spring. The songbirds' strategies involve elements of both drift and compensation, providing some benefits from wind in combination with destination and time control. In contrast, moths expose themselves to a significantly higher degree of drift in order to obtain strong wind assistance, surpassing the songbirds in mean ground speed, at the cost of a comparatively lower spatiotemporal migratory precision. Moths and songbirds show contrasting but adaptive responses to migrating through a moving flow, which are fine-tuned to the respective flight capabilities of each group in relation to the wind currents they travel within.


Subject(s)
Adaptation, Physiological , Animal Migration , Flight, Animal , Moths/physiology , Songbirds/physiology , Wind , Animals , Radar , Seasons , Sweden
9.
Biol Lett ; 11(6): 20150337, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26085501

ABSTRACT

In order to fully understand the orientation behaviour of migrating birds, it is important to understand when birds set their travel direction. Departure directions of migratory passerines leaving stopover sites are often assumed to reflect the birds' intended travel directions, but this assumption has not been critically tested. We used data from an automated radiotelemetry system and a tracking radar at Falsterbo peninsula, Sweden, to compare the initial orientation of departing songbirds (recorded by radiotelemetry) with the orientation of songbird migrants in climbing and level flight (recorded by radar). We found that the track directions of birds at high altitudes and in level flight were more concentrated than the directions of departing birds and birds in climbing flight, which indicates that the birds adjust their travelling direction once aloft. This was further supported by a wide scatter of vanishing bearings in a subsample of radio-tracked birds that later passed an offshore radio receiver station 50 km southeast of Falsterbo. Track directions seemed to be more affected by winds in climbing compared with level flights, which may be explained by birds not starting to partially compensate for wind drift until they have reached cruising altitudes.


Subject(s)
Animal Migration , Flight, Animal , Orientation , Songbirds/physiology , Animals , Radar , Sweden , Telemetry , Wind
10.
Mod Pathol ; 27(9): 1223-30, 2014 09.
Article in English | MEDLINE | ID: mdl-24457463

ABSTRACT

Male breast cancer is poorly understood with a large proportion arising in the familial context particularly with the BRCA2 germline mutation. As phenotypic and genotypic differences between sporadic and familial male breast cancers have been noted, we investigated the importance of a hypoxic drive in these cancers as this pathway has been shown to be of importance in familial female breast cancer. Expression of two major hypoxia-induced proteins, the hypoxia-inducible factor-1α (HIF1A) and the carbonic anhydrase IX (CA9), examined within a large cohort including 61 familial (3 BRCA1, 28 BRCA2, 30 BRCAX) and 225 sporadic male breast cancers showed that 31% of all male breast cancers expressed either HIF1A (25%) and/or CA9 (8%) in the combined cohort. Expression of HIF1A correlated with an increased incidence of a second-major malignancy (P=0.04), histological tumor type (P=0.005) and basal phenotype (P=0.02). Expression of CA9 correlated with age (P=0.004) in sporadic cases and an increased tumor size (P=0.003). Expression of HIF1A was prognostic for disease-specific survival in sporadic male breast cancers (HR: 3.8, 95% CI: 1.5-9.8, P=0.006) but not within familial male breast cancer, whereas CA9 was only prognostic in familial male breast cancers (HR: 358.0, 95% CI: 9.3-13781.7, P=0.002) and not in sporadic male breast cancer. This study found that hypoxic drive is less prevalent in male breast cancer compared with female breast cancer, possibly due to a different breast microenvironment. The prognostic impact of HIF1A is greatest in sporadic male breast cancers with an alternate dominant mechanism for the oncogenic drivers suggested in high risk familial male breast cancers.


Subject(s)
Biomarkers, Tumor/metabolism , Breast Neoplasms, Male/metabolism , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Aged , Antigens, Neoplasm/genetics , BRCA1 Protein/metabolism , BRCA2 Protein/metabolism , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Breast Neoplasms, Male/diagnosis , Breast Neoplasms, Male/mortality , Carbonic Anhydrase IX , Carbonic Anhydrases/genetics , Disease-Free Survival , Female , Genetic Predisposition to Disease , Germ-Line Mutation , Humans , Immunohistochemistry , Male , Prognosis , Tissue Array Analysis
11.
Acta Obstet Gynecol Scand ; 93(5): 517-20, 2014 May.
Article in English | MEDLINE | ID: mdl-24754607

ABSTRACT

The objective was to compare two teaching methods for postpartum hemorrhage management: interactive hands-on training and non-interactive video training. In a controlled intervention study at a secondary health care center in Kenya, the two training methods, based on the Advanced Life Support in Obstetrics curriculum, were evaluated utilizing structured observation of a standardized scenario before and after training. Both intervention groups significantly increased in performance scores after receiving hands-on training: 40% (95% CI 29.5-47.0) and video training: 34.5% (95% CI 25.0-42.0); likewise, pass rates improved significantly. No significant differences in performance score or pass rates were found between the two methods. The findings indicate that postpartum hemorrhage management training by mobile media might be just as effective as conventional hands-on training and a feasible way to overcome the outreach gap in sub-Saharan Africa's rural areas, where peripheral health facilities are generally difficult to reach with conventional training programs.


Subject(s)
Education, Nursing/methods , Obstetrics/education , Postpartum Hemorrhage/therapy , Rural Health Services , Adult , Clinical Competence , Female , Humans , Kenya , Male , Video Recording , Young Adult
12.
Am Nat ; 181(6): 837-45, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23669545

ABSTRACT

It has been suggested that birds migrate faster in spring than in autumn because of competition for arrival order at breeding grounds and environmental factors such as increased daylight. Investigating spring and autumn migration performances is important for understanding ecological and evolutionary constraints in the timing and speed of migration. We compiled measurements from tracking studies and found a consistent predominance of cases showing higher speeds and shorter durations during spring compared to autumn, in terms of flight speeds (airspeed, ground speed, daily travel speed), stopover duration, and total speed and duration of migration. Seasonal differences in flight speeds were generally smaller than those in stopover durations and total speed/duration of migration, indicating that rates of foraging and fuel deposition were more important than flight speed in accounting for differences in overall migration performance. Still, the seasonal differences in flight speeds provide important support for time selection in spring migration.


Subject(s)
Animal Migration , Birds , Seasons , Animals , Feeding Behavior , Models, Biological , Models, Statistical , Time Factors
13.
Mod Pathol ; 26(1): 87-94, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22918167

ABSTRACT

Assessment of proliferation is important in female breast cancer and individual treatment decisions are based upon its results, especially in the luminal subgroups. Gene expression analyses fail to group male breast cancer into the intrinsic subgroups previously established in female breast cancer. Even though proliferation has been shown to divide male breast cancer into molecular subgroups with different prognoses, the clinical importance of proliferation markers has not yet been elucidated. Previous studies in male breast cancer have demonstrated contradictory results regarding the prognostic impact of histological grade and Ki-67, parameters strongly associated with proliferation. The aim of the present project was to study proliferation in male breast cancer by assessing other proliferation-related markers viz. cyclins A, B, D1 and mitotic count. A total of 197 male breast cancer cases with accessible paraffin-embedded material and outcome data were investigated. Immunohistochemical stainings were performed on tissue microarrays. Kaplan-Meier estimates and the Cox proportional regression models were used for survival analyses with breast cancer death as the event. The subset of patients with high expression of cyclin A (hazard ratio (HR) 3.7; P=0.001) and B (HR 2.7; P=0.02) demonstrated a poorer survival. Furthermore, high mitotic count was associated with an increased risk of breast cancer death (HR 2.5; P=0.01). In contrast, cyclin D1 overexpression was predictive of better breast cancer survival (HR 0.3; P=0.001). In conclusion, high levels of cyclin A and B expression and an elevated mitotic count result in a two to threefold higher risk for breast cancer death, whereas cyclin D1 overexpression halves the risk. The clinical utility of these proliferation markers needs further elucidation.


Subject(s)
Biomarkers, Tumor/analysis , Breast Neoplasms, Male/mortality , Breast Neoplasms, Male/pathology , Adult , Aged , Aged, 80 and over , Breast Neoplasms, Male/metabolism , Cell Proliferation , Cyclin A/analysis , Cyclin A/biosynthesis , Cyclin B/analysis , Cyclin B/biosynthesis , Cyclin D1/analysis , Cyclin D1/biosynthesis , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Middle Aged , Mitotic Index , Neoplasm Grading , Neoplasm Staging , Tissue Array Analysis , Young Adult
14.
Acta Oncol ; 52(1): 102-9, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22928693

ABSTRACT

BACKGROUND: Male breast cancer (MBC) is an uncommon disease and there is limited information on the prognostic impact of routinely used clinicopathological parameters. MATERIAL AND METHODS: In a retrospective setting, we reviewed 197 MBC patients with accessible paraffin-embedded tumor tissue and clinicopathological data. Immunohistochemical (IHC) stainings were performed on tissue microarrays and histological grading on conventional slides. Cox proportional regression models were applied for uni- and multivariate analyses using breast cancer death as the event. RESULTS: Estrogen receptor (ER) and progesterone receptor positivity were demonstrated in 93% and 77% of patients, respectively. Nottingham histologic grade (NHG) III was seen in 41% and HER2 positivity in 11%. Classification into molecular subtypes using IHC markers according to three alternative definitions revealed luminal A and luminal B in 81% vs. 11%; 48% vs. 44% and 41% vs. 42% of cases. Two cases of basal-like were identified, but no cases of HER2-like. Factors associated with an increased risk of breast cancer death were node positivity (HR 4.5; 95% CI 1.8-11.1), tumor size > 20 mm (HR 3.3; 95% CI 1.4-7.9) and ER negativity (HR 10.9; 95% CI 3.2-37.9). No difference in breast cancer death between the luminal subgroups was demonstrated, regardless of definition. CONCLUSION: MBC tumors were more often of high grade, whereas HER2 overexpression was as frequent as in FBC. Lymph nodes, tumor size and ER status were independent predictors of breast cancer death. The prognostic impact of molecular subtyping in MBC seems to differ from that previously established in FBC.


Subject(s)
Breast Neoplasms, Male/mortality , Breast Neoplasms, Male/pathology , Adult , Aged , Aged, 80 and over , Breast Neoplasms, Male/metabolism , Humans , Immunohistochemistry , Ki-67 Antigen/metabolism , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local , Prognosis , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Registries , Retrospective Studies , Tissue Array Analysis , Young Adult
15.
Breast Cancer Res ; 14(1): R31, 2012 Feb 14.
Article in English | MEDLINE | ID: mdl-22333393

ABSTRACT

INTRODUCTION: Male breast cancer (MBC) is a rare and inadequately characterized disease. The aim of the present study was to characterize MBC tumors transcriptionally, to classify them into comprehensive subgroups, and to compare them with female breast cancer (FBC). METHODS: A total of 66 clinicopathologically well-annotated fresh frozen MBC tumors were analyzed using Illumina Human HT-12 bead arrays, and a tissue microarray with 220 MBC tumors was constructed for validation using immunohistochemistry. Two external gene expression datasets were used for comparison purposes: 37 MBCs and 359 FBCs. RESULTS: Using an unsupervised approach, we classified the MBC tumors into two subgroups, luminal M1 and luminal M2, respectively, with differences in tumor biological features and outcome, and which differed from the intrinsic subgroups described in FBC. The two subgroups were recapitulated in the external MBC dataset. Luminal M2 tumors were characterized by high expression of immune response genes and genes associated with estrogen receptor (ER) signaling. Luminal M1 tumors, on the other hand, despite being ER positive by immunohistochemistry showed a lower correlation to genes associated with ER signaling and displayed a more aggressive phenotype and worse prognosis. Validation of two of the most differentially expressed genes, class 1 human leukocyte antigen (HLA) and the metabolizing gene N-acetyltransferase-1 (NAT1), respectively, revealed significantly better survival associated with high expression of both markers (HLA, hazard ratio (HR) 3.6, P = 0.002; NAT1, HR 2.5, P = 0.033). Importantly, NAT1 remained significant in a multivariate analysis (HR 2.8, P = 0.040) and may thus be a novel prognostic marker in MBC. CONCLUSIONS: We have detected two unique and stable subgroups of MBC with differences in tumor biological features and outcome. They differ from the widely acknowledged intrinsic subgroups of FBC. As such, they may constitute two novel subgroups of breast cancer, occurring exclusively in men, and which may consequently require novel treatment approaches. Finally, we identified NAT1 as a possible prognostic biomarker for MBC, as suggested by NAT1 positivity corresponding to better outcome.


Subject(s)
Arylamine N-Acetyltransferase/metabolism , Biomarkers, Tumor/metabolism , Breast Neoplasms, Male/enzymology , Carcinoma, Ductal, Breast/enzymology , Carcinoma, Intraductal, Noninfiltrating/enzymology , Isoenzymes/metabolism , Transcriptome , Adult , Aged , Aged, 80 and over , Arylamine N-Acetyltransferase/genetics , Biomarkers, Tumor/genetics , Breast Neoplasms, Male/classification , Breast Neoplasms, Male/diagnosis , Breast Neoplasms, Male/mortality , Carcinoma, Ductal, Breast/classification , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Ductal, Breast/mortality , Carcinoma, Intraductal, Noninfiltrating/classification , Carcinoma, Intraductal, Noninfiltrating/diagnosis , Carcinoma, Intraductal, Noninfiltrating/mortality , Cluster Analysis , Female , Gene Expression Profiling , Humans , Isoenzymes/genetics , Kaplan-Meier Estimate , Male , Middle Aged , Multivariate Analysis , Oligonucleotide Array Sequence Analysis , Principal Component Analysis , Prognosis , Statistics, Nonparametric , Tissue Array Analysis , Young Adult
16.
Acta Pharmacol Sin ; 33(2): 173-81, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22301857

ABSTRACT

Obesity and obesity-related metabolic diseases represent a growing socioeconomic problem throughout the world. Great emphasis has been put on establishing treatments for this condition, including pharmacological intervention. However, there are many obstacles and pitfalls in the development process from pre-clinical research to the pharmacy counter, and there is no certainty that what has been observed pre-clinically will translate into an improvement in human health. Hence, it is important to test potential new drugs in a valid translational model early in their development. In the current mini-review, a number of monogenetic and polygenic models of obesity will be discussed in view of their translational character.


Subject(s)
Disease Models, Animal , Obesity/pathology , Translational Research, Biomedical , Animals , Diet , Humans , Mice , Obesity/genetics , Obesity/metabolism , Rats , Translational Research, Biomedical/methods
17.
Cancers (Basel) ; 14(4)2022 Feb 18.
Article in English | MEDLINE | ID: mdl-35205786

ABSTRACT

The benefit of imaging in the follow-up setting for high-risk melanoma patients is uncertain, and even less is known about the impact of intensive follow-up on the patient´s quality of life. In 2017, a Swedish prospective randomized multicenter study started, in which high-risk melanoma patients are randomly assigned 1:1 to follow-up by physical examinations +/- whole-body imaging. The first-year examinations are scheduled at 0, 6 and 12 months. The aim of this study was to investigate whether the patients´ health-related quality of life (HRQoL) and levels of anxiety and depression were affected at 1 year by imaging. Anxiety/depression and HRQoL were assessed at 0 and 12 months by the questionnaires Hospital Anxiety and Depression (HAD) scale and EORTC QLQ-C30 version 3. Expected baseline QLQ-C30 values for the patients were calculated using data from the general population. In total, 204 patients were analyzed. Mean differences in subscale scores at 1 year were not statistically significant either for HRQoL or for anxiety/depression. Baseline HRQoL did not differ from expected values in the general Swedish population. In conclusion, the patients in general coped well with the situation, and adding whole-body imaging to physical examinations did not affect the melanoma patients' HRQoL or levels of anxiety or depression.

18.
Breast Cancer Res Treat ; 129(3): 747-60, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21113657

ABSTRACT

Male breast cancer (MBC) is extremely rare and poorly characterized on the molecular level. Using high-resolution genomic data, we aimed to characterize MBC by genomic imbalances and to compare it with female breast cancer (FBC), and further to investigate whether the genomic profiles hold any prognostic information. Fifty-six fresh frozen MBC tumors were analyzed using high-resolution tiling BAC arrays. Significant regions in common between cases were assessed using Genomic Identification of Significant Targets in Cancer (GISTIC) analysis. A publicly available genomic data set of 359 FBC tumors was used for reference purposes. The data revealed a broad pattern of aberrations, confirming that MBC is a heterogeneous tumor type. Genomic gains were more common in MBC than in FBC and often involved whole chromosome arms, while losses of genomic material were less frequent. The most common aberrations were similar between the genders, but high-level amplifications were more common in FBC. We identified two genomic subgroups among MBCs; male-complex and male-simple. The male-complex subgroup displayed striking similarities with the previously reported luminal-complex FBC subgroup, while the male-simple subgroup seems to represent a new subgroup of breast cancer occurring only in men. There are many similarities between FBC and MBC with respect to genomic imbalances, but there are also distinct differences as revealed by high-resolution genomic profiling. MBC can be divided into two comprehensive genomic subgroups, which may be of prognostic value. The male-simple subgroup appears notably different from any genomic subgroup so far defined in FBC.


Subject(s)
Breast Neoplasms, Male/genetics , Breast Neoplasms/genetics , Adult , Aged, 80 and over , BRCA2 Protein/genetics , Chromosome Aberrations , Comparative Genomic Hybridization , Female , Humans , Male , Middle Aged , Mutation
19.
Proc Biol Sci ; 278(1721): 3074-80, 2011 Oct 22.
Article in English | MEDLINE | ID: mdl-21389024

ABSTRACT

Vast numbers of insects and passerines achieve long-distance migrations between summer and winter locations by undertaking high-altitude nocturnal flights. Insects such as noctuid moths fly relatively slowly in relation to the surrounding air, with airspeeds approximately one-third of that of passerines. Thus, it has been widely assumed that windborne insect migrants will have comparatively little control over their migration speed and direction compared with migrant birds. We used radar to carry out the first comparative analyses of the flight behaviour and migratory strategies of insects and birds under nearly equivalent natural conditions. Contrary to expectations, noctuid moths attained almost identical ground speeds and travel directions compared with passerines, despite their very different flight powers and sensory capacities. Moths achieved fast travel speeds in seasonally appropriate migration directions by exploiting favourably directed winds and selecting flight altitudes that coincided with the fastest air streams. By contrast, passerines were less selective of wind conditions, relying on self-powered flight in their seasonally preferred direction, often with little or no tailwind assistance. Our results demonstrate that noctuid moths and passerines show contrasting risk-prone and risk-averse migratory strategies in relation to wind. Comparative studies of the flight behaviours of distantly related taxa are critically important for understanding the evolution of animal migration strategies.


Subject(s)
Animal Migration , Flight, Animal , Moths/physiology , Songbirds/physiology , Air Movements , Altitude , Animals , England , Orientation , Radar , Seasons
20.
Acta Oncol ; 50(7): 1083-8, 2011 Oct.
Article in English | MEDLINE | ID: mdl-21830994

ABSTRACT

PURPOSE: Male breast cancer (MBC) is an uncommon disease. In the absence of randomized studies, current guidelines are mainly based on data on the management of female breast cancer (FBC). In light of concerns regarding the quality and extent of management in men, the aim of the present study was to investigate whether there are differences in tumor characteristics, treatment and outcome in male compared with FBC patients. METHODS: Cohorts of male and female breast cancer were retrospectively analyzed. All male patients diagnosed with invasive breast cancer between 1993 and 2007 were identified from the Regional Breast Cancer Register of the Uppsala-Örebro Region in Sweden. To increase the power of the study and obtain comparable cohorts we sampled four FBC patients (n = 396) for each MBC patient (n = 99) with similar age at diagnosis and time of diagnosis. RESULTS: No differences were seen in stage at diagnosis between MBC and FBC. Men underwent mastectomy more often than women (92% vs. 44%, p < 0.001). Radiotherapy was delivered less often to MBC than FBC (44% vs. 56%, p = 0.034), but radiotherapy given after mastectomy (44% vs. 39%, p = 0.47) did not differ between the groups. No differences were found regarding adjuvant chemotherapy (16% vs. 21%; p = 0.31) or adjuvant endocrine therapy (59% vs. 52%, p = 0.24). Both overall survival (41% vs. 55%, p = 0.001) and relative survival (74% vs. 88%, p = 0.015) were inferior in MBC compared to FBC. CONCLUSION: Concerns regarding less extensive treatment in MBC patients were not supported by this study. Although no differences in the stage of the disease or treatment intensity could be demonstrated, outcome was inferior in the male group.


Subject(s)
Breast Neoplasms, Male , Breast Neoplasms , Adult , Age Factors , Aged , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Breast Neoplasms/physiopathology , Breast Neoplasms/therapy , Breast Neoplasms, Male/mortality , Breast Neoplasms, Male/pathology , Breast Neoplasms, Male/physiopathology , Breast Neoplasms, Male/therapy , Chemotherapy, Adjuvant , Combined Modality Therapy , Female , Humans , Male , Mastectomy , Middle Aged , Neoplasm Recurrence, Local , Neoplasm Staging , Retrospective Studies , Sex Factors , Survival Analysis , Sweden , Young Adult
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