Improved detection of chromosomal abnormalities in chronic lymphocytic leukemia by conventional cytogenetics using CpG oligonucleotide and interleukin‐2 stimulation: A Belgian multicentric study

We performed a multicentric study to assess the impact of two different culture procedures on the detection of chromosomal abnormalities in 217 consecutive unselected cases with chronic lymphocytic leukemia (CLL) referred for routine analysis either at the time of diagnosis (n = 172) or during disease evolution (n = 45). Parallel cultures of peripheral blood or bone marrow were set up with the addition of either the conventional B‐cell mitogen 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA) or a combination of CpG oligonucleotide (CpG) and interleukin‐2 (IL‐2). Cytogenetic analyses were performed on both cultures. Clonal abnormalities were identified in 116 cases (53%). In 78 cases (36%), the aberrant clone was detected in both cultures. Among these, the percentages of aberrant metaphases were similar in both conditions in 17 cases, higher in the CpG/IL‐2 culture in 43 cases, and higher in the TPA culture in 18 cases. Clonal aberrations were detected in only one culture, either in CpG/IL‐2 or TPA in 33 (15%) and 5 (2%) cases, respectively. Taken together, abnormal karyotypes were observed in 51% with CpG/IL‐2 and 38% with TPA (P < 0.0001). Application of FISH (n = 201) allowed the detection of abnormalities not visible by conventional cytogenetic analysis in 80 cases: del(13q) (n = 71), del(11q) (n = 5), +12 (n = 2), del(14q) (n = 1), and del(17p) (n = 1). In conclusion, our results confirm that CpG/IL‐2 stimulation increases the detection rate of chromosomal abnormalities in CLL compared with TPA and that further improvement can be obtained by FISH. However, neither conventional cytogenetics nor FISH detected all aberrations, demonstrating the complementary nature of these techniques. © 2009 Wiley‐Liss, Inc.     

Variations in HSP70 genes associated with noise-induced hearing loss in two independent populations

Noise-induced hearing loss (NIHL) is one of the most important occupational health hazards. Millions of people worldwide are exposed daily to harmful levels of noise. NIHL is a complex disease resulting from an interaction between genetic and environmental factors. Although the environmental risk factors have been studied extensively, little is known about the genetic factors. Heat-shock proteins (HSPs) are induced after exposure to severe noise. When first induced by exposure to moderate sound levels, they can protect the ear from damage from excessive noise exposure. This protection is highly variable between individuals. An association of HSP70 genes with NIHL has been described by Yang et al (2006) in a Chinese sample set of noise-exposed workers. In this study, three polymorphisms (rs1043618, rs1061581 and rs2227956) in HSP70-1, HSP70-2 and HSP70-hom, respectively, were genotyped in 206 Swedish and 238 Polish DNA samples of noise-exposed subjects and analyzed. One SNP, rs2227956 in HSP70-hom, resulted in a significant association with NIHL in both sample sets. In addition, rs1043618 and rs1061581 were significant in the Swedish sample set. Analysis of the haplotypes composed of the three SNPs revealed significant associations between NIHL and haplotype GAC in both sample sets and with haplotype CGT in the Swedish sample set. In conclusion, this study replicated the association of HSP70 genes with NIHL in a second and third independent noise-exposed sample set, hereby adding to the evidence that HSP70 genes may be NIHL susceptibility genes.     

Factors associated with cancer worries in individuals participating in annual pancreatic cancer surveillance

It is important to adequately and timely identify individuals with cancer worries amongst participants in a pancreatic ductal adenocarcinoma (PDAC) surveillance program, because they could benefit from psychosocial support to decrease distress. Therefore, the aim of this study was to assess both psychosocial and clinical factors associated with cancer worries. High-risk individuals participating in PDAC-surveillance were invited to annually complete a cancer worry scale (CWS) questionnaire which was sent after counseling by the clinical geneticist (T0), after intake for participation in PDAC-surveillance (T1), and then annually after every MRI and endoscopic ultrasonography (EUS) (T2 and further). Analyses were performed to identify factors associated with cancer worries in the second year of surveillance (T3). We found a significant intra-individual decrease in cancer worries (β = ?0.84, P < 0.001), nevertheless, 33 % of individuals had a CWS-score ≥14 at T3. We found one factor significantly associated with cancer worries at T3: having a family member affected by PDAC <50 years of age (β = 0.22, P = 0.03). The detection of a cystic lesion, a shortened surveillance interval, or undergoing pancreatic surgery did not lead to more cancer worries (P = 0.163, P = 0.33, and P = 0.53, respectively). In conclusion, this study identified ‘a family history of PDAC <50 years of age’ as the only predictor of cancer worries experienced after 2 years of surveillance in individuals at high risk of developing PDAC. This knowledge could help clinicians to timely identify individuals ‘at risk’ for high levels of cancer worries who would likely benefit from psychosocial support.     

Menopausal hormone therapy and the risk of esophageal and gastric cancer

A protective effect of female sex hormones has been suggested to explain the male predominance in esophageal and gastric adenocarcinoma, but evidence is lacking. We aimed to test whether menopausal hormone therapy (MHT) decreases the risk of these tumors. For comparison, esophageal squamous cell carcinoma was also assessed. This population‐based matched cohort study included all women who had ever used systemic MHT in Sweden in 2005–2012. A comparison cohort of non‐users of MHT was matched to the MHT‐users regarding age, parity, thrombotic events, hysterectomy, diabetes, obesity, smoking‐related diseases and alcohol‐related diseases. Individuals with any previous cancer were excluded. Data on MHT use, cancer, comorbidity and mortality were collected from well‐established Swedish nationwide registers. Odds ratios (OR) with 95% confidence intervals (CI) were calculated using conditional logistic regression. Different MHT regimens and age groups were compared in sub‐group analyses. We identified 290,186 ever‐users and 870,165 non‐users of MHT. Ever‐users had decreased ORs of esophageal adenocarcinoma (OR = 0.62, 95% CI 0.45–0.85, n = 46), gastric adenocarcinoma (OR = 0.61, 95% CI 0.50–0.74, n = 123) and esophageal squamous cell carcinoma (OR = 0.57, 95% CI 0.39–0.83, n = 33). The ORs were decreased for both estrogen‐only MHT and estrogen and progestin combined MHT, and in all age groups. The lowest OR was found for esophageal adenocarcinoma in MHT‐users younger than 60 years (OR = 0.20, 95% CI 0.06–0.65). Our study suggests that MHT‐users are at a decreased risk of esophageal and gastric adenocarcinoma and also of esophageal squamous cell carcinoma. The mechanisms behind these associations remain to be elucidated.     

Cytogenetic characterization of a high-grade murine B-cell lymphoma

The chromosomal pattern of a high-grade malignant B-cell lymphoma that arose spontaneously in a C57BL mouse is described. A considerable amount of structural chromosomal abnormalities was found in the lymphoma cells. These abnormalities are discussed in view of their possible role for oncogenesis, infiltration, and tissue distribution. The chromosomal findings of this lymphoma are compared with the few that have been described previously.     

Fusobacterium pyomyositis of the shoulder after tonsillitis. Report of a case of Lemierre's syndrome.

A case of nontropical pyomyositis is reported in a young male without predisposing factors. The disease was preceded by a tonsillitis, and the presentation initially suggested a septic arthritis of the shoulder. Fusobacterium, a highly unusual pathogen in pyomyositis, was isolated from an abscess in the infraspinatus muscle. The increasing frequency of the disease in areas with a temperate climate and the pathogenesis are discussed. Our case had the classic features of Lemierre's syndrome: invasion of the bloodstream by Fusobacterium species from a tonsillitis.     

PET measurements of hyperthermia-induced suppression of protein synthesis in tumors in relation to effects on tumor growth

Hyperthermia-induced metabolic changes in tumor tissue have been monitored by PET. Uptake of L-[1-11C]tyrosine in rhabdomyosarcoma tissue of Wag/Rij rats was dose-dependently reduced after local hyperthermia treatment at 42, 45, or 47 degrees C. Tumor blood flow, as measured by PET with 13NH3, appeared to be unchanged. The L-[1-11C]tyrosine uptake data were compared to uptake data of L-[1-14C]tyrosine and with data on the incorporation of L-[1-14C]tyrosine into tumor proteins. After intravenous injection, the 14C data were obtained from dissected tumor tissue. Heat-induced inhibition of the incorporation of L-[1-14C]tyrosine into tumor proteins tallied with the L-[1-11C]tyrosine uptake data. Heat-induced inhibition of amino acid uptake in the tumor correlated well with regression of tumor growth. It is concluded that PET using L-[1-11C]tyrosine is eligible for monitoring the effect of hyperthermia on tumor growth.     

Heat-induced nuclear protein binding and its relation to thermal cytotoxicity

When nuclei were isolated from exponentially growing HeLa S3 cells immediately after a treatment with hyperthermia and/or procaine-HCl, an increase in nuclear protein binding was observed. The extent of this increase, however, did not correlate with cell survival under all conditions of the various treatments. For example, an increase up to 40 per cent in nuclear protein binding as a result of procaine treatment did not lead to a decrease of survival, while a 40 percent increase of nuclear protein binding as a result of hyperthermia corresponded with over 90 per cent cell killing. In addition the extent of heat-induced enhancement of nuclear protein content was approximately equal for thermotolerant and heated control cells, or for cells heated in the presence of procaine. The rate of decay in nuclear protein binding upon post-heat incubations at 37 degrees C of the cells, however, was enhanced in tolerant cells and retarded in cells heated in the presence of procaine as compared to heated control cells. These results show that, in spite of suggestions in other reports, neither the initial rate of enhanced protein binding nor the extent of the protein bound to the nucleus seems a reliable measure for heat toxicity. The capacity of the cell to reverse this heat-induced protein binding must be considered.