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Thalidomide causes teratogenic effects in several animal species and in humans. Accordingly, the World Health Organization banned thalidomide when mothers who took thalidomide during pregnancy delivered abnormal fetuses. After four decades, thalidomide underwent drug “re-purposing” since its antiangiogenic and immunomodulatory effects were therapeutic for multiple myeloma. There are no reports of thalidomide’s effects on prokaryotes, but it showed teratogenic effects in Arabidopsis thaliana, an ancestor of the plant kingdom. This proof of concept study clearly shows that thalidomide caused a significant and reproducible decrease in germination rate, nitric oxide (NO) production, and chlorophyll content of fennel plantlets. Thalidomide also induced the formation of abnormal fennel plantlets with stunting, wrinkling, and curling of fennel shoots and leaves. Notably, quantitative analysis showed that thalidomide caused a 50% increase in the formation of abnormal fennel plantlets and that these negative effects of thalidomide showed a 2.50- to 4-fold decrease when fennel seeds were co-incubated with an NO donor (Spermine NoNoate) or a stable cGMP analog 8-bromo Guanosine 3′,5′-cyclic monophosphate (8-Bromo-cGMP). This study is important because it confirms that thalidomide’s negative effects on fennel seed germination and growth are mediated by attenuation of NO and disruption of NO signaling. This reproducible model of thalidomide-induced, NO-dependent damage in a plant system can be used to further investigate the molecular mechanisms of thalidomide action in plants. Importantly, this study establishes a link between the evolution of development of higher plants and mammals.

Objective Fear of cancer recurrence (FCR) is a common psychosocial sequela among cancer survivors, but data on patients with multiple myeloma are scarce. This study calculated the prevalence of FCR and identified family and social factors that predict FCR in the study population. Methods We recruited 127 myeloma patients and their partners to participate in a cross‐sectional survey from a regional tertiary cancer centre in China. The questionnaires included items on demographic characteristics and from the fear of disease progression simplified scale, family hardiness index and Social Support Scale. Univariate and multivariate regression was used to identify predictors of FCR. Results Of the participants, 56.4% patients reported high‐level FCR, which was similar to the partner‐reported proportion. The partners' FCR was positively associated with the patients' FCR, while family hardiness and social support were statistically significant, negative predictors. Conclusions Interventions to mitigate partners' FCR and improve family hardiness and social support may help with the psychological adjustment and well‐being of myeloma patients.

Circulating tumor cells (CTCs) are of great interest in cancer research because of their crucial role in hematogenous metastasis. We recently developed “diffuse in vivo flow cytometry” (DiFC), a preclinical research tool for enumerating extremely rare fluorescently labeled CTCs directly in vivo. In this work, we developed a green fluorescent protein (GFP)-compatible version of DiFC and used it to noninvasively monitor tumor cell numbers in circulation in a multiple myeloma (MM) disseminated xenograft mouse model. We show that DiFC allowed enumeration of CTCs in individual mice overtime during MM growth, with sensitivity below 1 CTC mL−1 of peripheral blood. DiFC also revealed the presence of CTC clusters (CTCCs) in circulation to our knowledge for the first time in this model and allowed us to calculate CTCC size, frequency, and kinetics of shedding. We anticipate that the unique capabilities of DiFC will have many uses in preclinical study of metastasis, in particular, with a large number of GFP-expressing xenograft and transgenic mouse models.

Introduction Non-epithelial breast malignancies include primary lymphomas, sarcomas, haematological malignancies, melanomas as well as secondary metastases to the breast. They account for less than 1% of all breast tumours. The demographics and clinical features are similar to epithelial breast cancers but the prognosis and management options are often very different. Most reported series are small with limited follow-up. The main aim of this study was to review our experience for these malignancies and to compare this with the published literature. Methods A 14-year retrospective review of all breast resection specimens was completed in the Antrim Area Hospital Cancer Unit. Clinical records of patients diagnosed with non-epithelial breast malignancies were then reviewed for data regarding patient demographics, clinical presentation, pre-operative investigations, operative findings and outcome. Pathology reports were examined carefully for tumour type, location and for evidence of lymphovascular spread. This data was compared with the available literature. Results Nineteen (F = 16) patients were found to have non-epithelial breast malignancies between April 1994 and August 2007. Mean age was 61.6 years (range 25–86). 17 patients (89.5%) presented with a palpable lump, mastalgia or skin change, while 2 (10.5%) patients' tumours were detected through screening. The histological types of non-epithelial malignancies were as follows: lymphoma (n = 8; M = 1 and F = 7, mean age: 68.5 range 52–86), sarcoma (n = 5; M = 1 and F = 4, mean age 56.4 range 29–69), malignant melanoma (n = 3; M = 1 and F = 2, mean age 54.3 range 25–70), multiple myeloma (n = 1; F, 71), metastatic renal cell carcinoma (n = 1; F, 63) and metastatic carcinoid tumour (n = 1; F, 52). The mean follow-up was 1541 days (32–4589 days). Nine patients were alive at the end of follow-up. Only 1 of 11 deaths was not directly related to the malignancy. The average time from surgery to death was 798.5 days (range 32–3248 days). Conclusion Non-epithelial breast malignancies are rare cancers with significant mortality rates. Correct diagnosis and avoidance of inappropriate therapies requires a comprehensive triple assessment and a multidisciplinary management approach.

Low-molecular-weight heparins (LMWH) appear to prolong survival of patients with cancer. Such a beneficial effect is thought to be associated with interruption of molecular mechanisms involving the heparan sulfate (HS) chains of cell surface and extracellular matrix proteoglycans (HSPGs), growth factors and their receptors, heparanase, and selectins. The beneficial effects of heparin species could also be associated with their ability to release tissue factor pathway inhibitor from endothelium. The utility of heparin and LMWH as anticancer drugs is limited due to their anticoagulant properties. Non-anticoagulant heparins can be obtained either by removing chains containing the antithrombin-binding sequence, or by inactivating critical functional groups or units of this sequence. The non-anticoagulant heparins most extensively studied are regioselectively desulfated heparins and ‘glycol-split’ heparins. Some modified heparins of both types are potent inhibitors of heparanase. A number of them also attenuate metastasis in experimental models. With cancer cells overexpressing selectins, heparin-mediated inhibition of tumor cells-platelets aggregation and tumor cell interaction with the vascular endothelium appears to be the prevalent mechanism of attenuation of early stages of metastasis. The structural requirements for inhibition of growth factors, heparanase, and selectins by heparin derivatives are somewhat different for the different activities. An N-acetylated, glycol-split heparin provides an example of application of a non-anticoagulant heparin that inhibits cancer in animal models without unwanted side effects. Delivery of this compound to mice bearing established myeloma tumors dramatically blocked tumor growth and progression.

A proportionate mortality ratio (PMR) analysis of 1071 deaths in pulp and paper mill workers in New Hampshire during 1975-85 showed an increase in cancers of the digestive tract and lymphopoietic tissues. A similar analysis of deaths for 452 timber cutters and loggers failed to show excess PMRs for cancers of these sites. Despite methodological constraints, these results suggest that one or more of the exposures experienced by pulp and paper mill workers may pose a significant carcinogenic risk. More definitive epidemiological studies are required to determine particular high risk processes or specific aetiological agents.

Three new human myeloma cell lines (U-1957, U-1958, and U-1996) have been established in vitro. The cell lines are Epstein-Barr virus (EBV) negative, monoclonal, and aneuploid and should thus represent malignant cell populations and not EBV-carrying non-neoplastic B lymphoblastoid cell lines. The myeloma origin of the cell lines is also suggested by their capacity for production of monoclonal complete immunoglobulin (Ig) molecules (U-1957 and U-1958) or IgG light chains (U-1996) of the same type as the myeloma protein in vivo. All the cell lines have morphological features of plasmablasts-plasma cells but appear to represent slightly different stages of B cell differentiation. Thus, the U-1958 has plasma cell morphology, expresses only PCA-1 and OKT-10 but no other B cell antigens, and secretes 1.5 micrograms/mL of IgG/10(6) cells/24 hours. The U-1957 has plasma cell morphology and expresses Fc receptors and the LB-1 antigen in addition to the PCA-1 and OKT-10 antigens. This line produces only minimal amounts of IgG, which appears not to be secreted. The U-1996, finally, is a kappa light chain producer, has a plasmablast morphology, and expresses LB-1 in addition to the PCA-1 and OKT-10 antigens. All three cell lines are chromosomally heterogeneous and contain several markers with a 14q+ abnormality as a common characteristic abnormality. These new myeloma lines have been in continuous culture for approximately 3 years and are instrumental in studies of various aspects of the biology of human myeloma.

Immunoglobulin D (IgD) has been recently established as a new fourth member of the immunoglobulin family. It was discovered by Rowe and Fahey1in 1965 in a patient with multiple myeloma and later it was found to be present in the serum of normal human subjects. Its biological functions and roles in the immune mechanisms are still unknown. D-myelomas are quite rare. Only a few reports have appeared in the literature.2-7 In the present communication a patient with plasma cell leukemia with IgD paraprotein will be described. This is, to our knowledge, the first reported case. Materials and Methods Routine hematological examinations were performed according to Dacie and Lewis.8Electrophoresis of serum and urine were done on paper, cellulose acetate, and starch gel according to techniques described by Kohn9and Smithies.10Immunoelectrophoresis and immunodiffusion of serum and urine were performed according to Scheidegger,11and