Traumatic distress symptoms in early breast cancer I: Acute response to diagnosis

In this study, the concept of ‘acute traumatic stress response’ was applied to breast cancer diagnosis. A total of 106 patients were studied before surgery, by means of a psychiatric interview and questionnaires (Impact of Event Scale, General Health Questionnaire and Clinical Global Impression Scale). The traumatic stress response was related to age, marital status, occurrence of breast cancer in first-degree relatives, previous physical and psychological health parameters, social support and life events during the last year. Of the patients, 44% reported a high level of intrusive symptoms (mean score 17.2) and 29% of avoidance symptoms (mean score 15.0). Younger age and being married were positively correlated with intrusive symptomology while patients with a first-degree relative with breast cancer had less intrusive distress. Previous physical and psychiatric health parameters showed no association to acute traumatic stress symptoms except for those who had experienced ‘a serious illness/accident/hospitalisation last year’ who had some more avoidant symptomology. Multiple regression showed a statistically significant effect for age only on intrusive symptoms when other factors were controlled for in this analysis.     

Traumatic distress symptoms in early breast cancer. II: Outcome six weeks post surgery

One hundred and six consecutive patients with a confirmed diagnosis of breast cancer were studied before and after surgery with a clinical psychiatric interview and questionnaires (Impact of Event Scale, General Health Questionnaire and Clinical Global Impression scale). The traumatic stress response after six weeks was related to sociodemographic factors, premorbid health problems, negative life events and clinical-oncological parameters. Symptoms of traumatic distress were significantly reduced post-surgery compared to acutely, and most so among patients with no premorbid health problems and negative life events according to pre-surgery interview and self-report data. Eighteen percent of the patients reported a high level (>19) of intrusive symptoms and 14%, avoidance symptoms. Patients with premorbid impairment in work, family and social functioning and patients who during the last year had experienced the death of a close relative or a serious illness other than cancer showed the greatest distress. Previous consultations for nervous problems, age, marital status, stage of disease, type of surgery (breast-conserving versus mastectomy) and adjuvant cytostatic treatment did not influence the traumaticstress response six weeks after surgery. The level of acute posttraumatic stress response to breast cancer surgery seems best predicted by premorbid variables.     

Absence of Neuronal Autoantibodies in Neuropsychiatric Systemic Lupus Erythematosus

This study aimed to characterise both neuronal autoantibodies and levels of interferon α, two proposed causative agents in neuropsychiatric systemic lupus erythematosus (NPSLE). Cerebrospinal fluid (CSF) and plasma from 35 patients with systemic lupus erythematosus (SLE; 15 with NPSLE) showed no antibodies against natively expressed N-methyl-D-aspartate receptors (NMDARs), or the surface of live hippocampal neurons. By comparison to controls (n = 104), patients with SLE had antibodies that bound to a peptide representing the extracellular domain of NMDARs (p < 0.0001), however, binding was retained against both rearranged peptides and no peptide (r = 0.85 and r = 0.79, respectively, p < 0.0001). In summary, neuronal-surface reactive antibodies were not detected in NPSLE. Further, while interferon α levels were higher in SLE (p < 0.0001), they lacked specificity for NPSLE. Our findings mandate a search for novel biomarkers in this condition. ANN NEUROL 2020;88:1244–1250     

Characterization of a hotspot region on chromosome 12 for amplification in ring chromosomes in atypical lipomatous tumors

Ring chromosomes are cytogenetic hallmarks of genomic amplification in several bone and soft tissue tumors, in particular atypical lipomatous tumors (ALT). In ALT, the ring chromosomes invariably contain amplified material from the central part of the long arm of chromosome 12, mainly 12q12→15, but often also segments from other chromosomes are involved. Previous studies have shown that one of the recurrent amplicons in ALT, located in 12q13.3‐14.1 and harboring the candidate target genes TSPAN31 and CDK4, often has a sharp centromeric border. To characterize this breakpoint region in more detail, 12 cases of ALT with ring chromosomes were analyzed by array comparative genomic hybridization and fluorescence in situ hybridization. In the seven cases showing a sharply delineated amplicon in 12q13.3‐14.1, the breakpoint region was further investigated by real time quantitative polymerase chain reaction and Vectorette PCR. The breakpoints clustered to a 146‐kb region containing 11 genes. Whereas there was no indication that the breakpoints gave rise to fusion genes, in silico analysis revealed that the breakpoint region was enriched for repeated elements that could be important for ring chromosome formation in ALT. © 2009 Wiley‐Liss, Inc.     

Indirect CD4+ T‐cell‐mediated elimination of MHC IINEG tumor cells is spatially restricted and fails to prevent escape of antigen‐negative cells

Tumor‐specific Th1 cells can activate tumor‐infiltrating macrophages that eliminate MHC class II negative (MHC II^NEG) tumor cells. Activated M1‐like macrophages lack antigen (Ag) receptors, and are presumably unable to discriminate and thus kill both Ag‐positive (Ag^POS) and Ag‐negative (Ag^NEG) tumor cells (bystander killing). The lack of specificity of macrophage‐mediated cytotoxicity might be of clinical importance as it could provide a means of avoiding tumor escape. Here, we have tested this idea using mixed populations of Ag^POS and Ag^NEG tumor cells in a TCR‐transgenic model in which CD4⁺ T cells recognize a secreted tumor‐specific antigen. Surprisingly, while Ag^POS tumor cells were recognized and rejected, Ag^NEG cells grew unimpeded and formed tumors. We further demonstrated that macrophage‐mediated cytotoxicity was spatially restricted to areas dominated by Ag^POS tumor cells, sparing Ag^NEG tumor cells in the vicinity. As a consequence, macrophage tumoricidal activity did not confer bystander killing in vivo. The present results offer novel insight into the mechanisms of indirect Th1‐mediated elimination of MHC II^NEG tumor cells.     

Dietary intake of phytoestrogens, estrogen receptor-beta polymorphisms and the risk of prostate cancer

BACKGROUND: The causes of prostate cancer are poorly understood, but genetic factors may be more important than for many other malignancies, and dietary phytoestrogens may be protective. Because phytoestrogens bind tightly to the estrogen receptor-beta, we conducted an epidemiologic investigation of synergistic effects between phytoestrogen intake and estrogen receptor-beta gene polymorphisms. METHODS: We performed a population-based case-control study in Sweden. All participants reported their phytoestrogen intake and donated a blood sample. We identified four haplotype-tagging single nucleotide polymorphisms (htSNPs) and genotyped these htSNPs in 1314 prostate cancer patients and 782 controls. Odds ratios were estimated by multivariate logistic regression. Interactions between phytoestrogen intake and estrogen receptor-beta SNPs on prostate cancer risk were evaluated considering both multiplicative and additive effect scales. RESULTS: We found a significant multiplicative interaction (P = 0.04) between dietary intake of phytoestrogens and a promoter SNP in the estrogen receptor-beta gene (rs 2987983-13950), but not with any of the three other htSNPs (P = 0.11, 0.69, 0.85). Among carriers of the variant promoter alleles, we found strong inverse associations with increasing intake of total phytoestrogens (odds ratio for highest vs. lowest quartile = 0.43; P for trend <0.001), isoflavonoids (odds ratio = 0.63; P for trend = 0.05), and coumestrol (odds ratio = 0.57; P for trend = 0.003). We found no association between phytoestrogens and prostate cancer among carriers homozygous for the wild-type allele (TT). CONCLUSIONS: Our study provides strong evidence that high intake of phytoestrogens substantially reduce prostate cancer risk among men with specific polymorphic variation in the promoter region of the estrogen receptor-beta gene.