Background and Objectives. Familial aggregation has been recognized in patients with several lymphoid neoplasms, but the genetic basis for this familial clustering is not known. Germ-line mutations in the ataxia-telangiectasia mutated (ATM) and CHK2 genes have been detected in patients with mantle cell lymphoma (MCL), suggesting a potential role of these genes in genetic predisposition to these tumors. However, no familial association has been previously recognized in MCL.

The molecular pathogenesis of follicular lymphoma (FL) was partially revealed 3 decades ago, with the discovery of the translocation that brings BCL2 under the influence of immunoglobulin heavy chain en-hancers in a vast majority of cases. Despite the importance of this seminal observation, it has become increasingly clear that additional genetic alterations need to occur to trigger neoplastic transformation and disease progression. The evolution of FL involves developmental arrest and disruption of the normal function of one or more of epigenetic regulators including KMT2D/MLL2, EZH2 , CBP/ CREBBP , p300/ EP300 , and HIST1H1 in > 95% of cases. B-cells "arrested" in germinal centers acquire dozens of additional genetic aberrations that influence key pathways controlling their physiological development including B Cell Receptor (BCR) signaling, PI3K/AKT, TLR, mTOR, NF-κB, JAK/STAT, MAPK, CD40/CD40L, chemokine, and interleukin signaling. Additionally, most cases of FL do not result from linear accumulation of ge-nomic aberrations, but rather evolve from a common progenitor cell population by diverse evolution, creating multiple FL subclones in one patient. Moreover, one of the subclones might acquire a combination of aberrations involving genes controlling cell survival and proliferation including MDM2, CDKN2A/B, BCL6, MYC, TP53, β2M, FOXO1, MYD88, STAT3, or miR-17-92 , and this can lead to the transformation of an initially indolent FL to an aggressive lymphoma (2%-3% risk per year). The complexity of the disease is also underscored by the importance of its interactions with the microenvironment that can substantially influence disease development and prognosis. Interpreting individual aberrations in relation to their impact on normal processes, their frequency, position in the disease evolution, and the consequences of their (co)occurrence, are the basis for understanding FL pathogenesis. This is necessary for the identification of patients with risk of early progression or transformation, for the development of novel targeted therapies, and for personalized treatment approaches. In this review, we summarize recent knowledge of molecular pathways and microenvironmental components involved in FL biology, and discuss them in the context of physiological B-cell development, FL evolution, and targeted therapies.

... The role of major histocompatibility complex class I antigens in tumorigenesis: future applications in cancer therapy. Auteur(s) / Author(s). NAPOLITANO L. (1) ; VOGEL J. ; JAY G. ; Affiliation(s) du ou des auteurs / Author(s) Affiliation(s). ... Tumor. ; Antígeno histocompatibilidad clase ...

56 patients receiving chemotherapy for non-Hodgkin lymphoma or Hodgkin's disease with curative intent were monitored for up to one year after initiation of treatment. During chemotherapy (mean duration 5.2 months), 26 of the patients (46') suffered from 38 febrile episodes. In only 16 instances was an extraoral cause for the septicaemia found. However, severe dental infection, reflected in an elevated radiological index for the jaws, was found more frequently in patients suffering febrile episodes than in those without (P= 0.02). Moderate to severe gingival inflammation was observed during 22 (58%) of episodes. During 71% of the episodes various pathological findings were also recorded in the oral mucosa. No source of infection other than an oral one was found in 42% of the patients. Our results emphasise the importance of oral foci as the possible infection source in patients receiving intensive chemotherapy.

A new generation of novel, effective targeted drugs and cellular therapies include monoclonal antibodies directed at the cell surface, such as the anti-CD-19 tafasitamab which, combined with lenalidomide, is the first therapy approved by the Food and Drug Administration for second-line treatment of diffuse large B-cell lymphoma. Other agents interfere with pro-survival intracellular signaling pathways including drugs that inhibit Bruton tyrosine kinase, phosphatidylinositol-3 kinase (PI3-kinase), and bcl-2. An increasing number of therapies impact the microenvironment, notably checkpoint inhibitors and bispecific antibodies. Chimeric antigen receptor-T cell therapy has improved the outcome of patients with a variety of histologies of lymphoma. Whereas in the past, such therapies would be used inrelapsed and refractory settings, they are now being evaluated as initial treatment in selected patients. With an improved ability to individualize treatment approaches, chemo-free will be a reality for lymphoma patients.

CARCINOMA of the large intestine is the leading cause of death from neoplastic disease in the United States and is therefore a major health problem. For reasons that are not readily apparent from epidemiologic studies, in America the incidence of this lesion is among the highest in the world. It is interesting to speculate on why the incidence of carcinoma of the colon in Japan is 6.6 males and 5.5 females per 100,000 population compared to 45.2 males and 49 females in the United States. Genetic factors are probably of little significance because the incidence in immigrants is similar to that in the population of the adopted rather than the native country.12 Another unexplained observation is the increasing proportion of colonic to rectal cancers throughout the United States.1 In 1968, the American Cancer Society estimates that there will be 73,000 new cases and 45,000 deaths due to cancer of the colon and rectum in this country.3 In view of the tremendous efforts in treatment of this disease, a review of 30 years' experience with cancer of the colon and rectum at The New York Hospital-Cornell Medical Center was undertaken. Clinical Material The records of 1,625 patients with carcinoma of the colon and rectum who were admitted to the pavilion service of The New York Hospital-Cornell Medical Cen

The cytokine interleukin 2 (IL-2) is involved in the activation of T cells and has been shown to play a central role in cancer immunotherapy. The full therapeutic potential of IL-2, however, has not been realized because of its doselimiting systemic toxicity. We sought to identify a region of IL-2 that is responsible for the induction of vasopermeability (leaky tumor endothelium), a property associated with the toxicity of the molecule. Methods: Intact IL-2 or overlapping synthetic peptides of IL-2 that were chemically conjugated to tumor-targeting monoclonal antibodies (TNT-1 or Lym-1) were injected into groups of mice (n = 4) that had previously been xenotransplanted with human tumor cells (ME-180 cervical carcinoma and Raji lymphoma). Two hours later, mice received intravenous injections of radiolabeled tracer antibody, and 3 days later they were subjected to biodistribution analysis to measure the ability of each immunoconjugate to enhance tumor uptake of the tracer antibody (i.e., vasopermeability activity). The cytokine activity of the immunoconjugates was determined by assaying their ability to promote the proliferation of a mouse IL-2-dependent cell line. Results: Pretreatment of mice with an antibody/IL-2 immunoconjugate resulted in an approximately fourfold increase in radiolabeled tracer antibody uptake in the xenograft tumor as compared with uptake in mice injected with antibody alone. One synthetic fragment consisting of amino acids 22-58 contained 100% of the vasopermeability activity of IL-2 and was designated permeability-enhancing peptide (PEP). PEP had vasopermeability activity only when conjugated to a tumor-targeting antibody, had maximal activity as a dimer, and was devoid of cytokine activity. Conclusions: The identification of PEP should aid in the discovery of ways to decrease the toxicity of IL-2. Moreover, PEP is a promising candidate for the generation of agents that can enhance the delivery of antibodies and drugs to tumors. [J Natl Cancer Inst 2003;95:741-9]

This paper describes the synthesis, physico-chemical characteristics and results of selected biological tests of conjugates of antibodies or proteins with poly(HPMA) or with poly(HPMA) carriers of anti-cancer drug doxorubicin, designed for targeted cancer therapy. Two types of conjugates differing in the method of conjugation of polymer with protein were synthesized. In the first, protein is attached to the polymer via an oligopeptide sequence in the side chain of the polymer backbone and, in the second, the polymer is attached to protein via its end-chain functional group. Conjugation of an antibody with poly(HPMA) does not influence the binding activity of the antibody for cell surface antigen. The physico-chemical characteristics and biological activity of both systems depend on the detailed structure of the polymer, the type of antibody or protein moiety and the structure of the whole system.

The main objective was to compare parent-reported health-related quality of life (HRQL) of child and adolescent survivors of childhood cancer to that of controls who had no history of cancer. Methods We assessed HRQL of 800 child and adolescent survivors younger than 16 years and 923 randomly selected, age-and sex-matched controls from the general population in a national multicenter retrospective cohort study using the Child Health Questionnaire parent report. Participation was 69% among survivors and 57% among controls. Results Survivors had means that were consistently lower than controls on the HRQL physical summary (PH; 49.9 v 55.3; P Ͻ.005), psychosocial summary (PS; 49.4 v 52.6; P Ͻ .005), and all but one of the eight subscale scores. Clinically important survivor-control differences in means on PH were found for survivors of CNS tumors, bone tumors, lymphoma, leukemia, soft tissue sarcoma and Wilms' tumor (differences: Ϫ8.7, Ϫ7.0, Ϫ6.3, Ϫ5.4, Ϫ4.4, Ϫ3.8/100, respectively); on PS, survivors of CNS tumors were most compromised (Ϫ6.1/100). Survivor-control differences in both PH and PS were also large for survivors treated with radiation only (Ϫ5.8 and Ϫ11.9/100, respectively), or radiation combined with surgery (Ϫ6.6 and Ϫ5.9/100, respectively), or radiation combined with both surgery and chemotherapy (Ϫ7.8 and Ϫ5.1/100, respectively). Cranial radiation was associated with the most compromised HRQL. Conclusion According to parents, HRQL for survivors was somewhat poorer, overall, than for controls. Survivors of CNS tumors, lymphoma, and leukemia and those patients treated with cranial radiation were reported to have poorest HRQL. These findings support development of guidelines for levels of follow-up care for particular groups of survivors.

Cover: This is a photograph of a model posing as a patient with Hu-PNS. Hu-PNS usually runs a severe and subacute course, leaving the patient with severe disability within weeks to months from onset of symptoms. At the time of neurological presentation, approximately 70% of patients are not known with cancer. In more than 80% of the patients, an underlying tumor is ultimately detected, most often a small cell lung cancer.

Computed tomography (CT; unenhanced, followed by contrast-enhanced examinations) is the cornerstone of imaging of adrenal tumours. Attenuation values of !10 Hounsfield units on an unenhanced CT are practically diagnostic for adenomas. When lesions cannot be characterised adequately with CT, magnetic resonance imaging (MRI) evaluation (with T1-and T2-weighted sequences and chemical shift and fat-suppression refinements) is sought. Functional nuclear medicine imaging is useful for adrenal lesions that are not adequately characterised with CT and MRI. Scintigraphy with [ 131 I]-6-iodomethyl norcholesterol (a labelled cholesterol analogue) can differentiate adrenal cortical adenomas from carcinomas. Phaeochromocytomas appear as areas of abnormal and/or increased uptake of [ 123 I]-and [ 131 I]-meta-iodobenzylguanidine (a labelled noradrenaline analogue). The specific and useful roles of adrenal imaging include the characterisation of tumours, assessment of true tumour size, differentiation of adenomas from carcinomas and metastases, and differentiation of hyperfunctioning from non-functioning lesions. Adrenal imaging complements and assists the clinical and hormonal evaluation of adrenal tumours.

Antibodies directed against tumourassociated antigens on cell surfaces can be used to carry cytotoxic agents specifically to tumour cells provided the antibody and agent are covalently bound. Physically adsorbed, but non-covalently bound, antibody/cytotoxic drug mixtures dissociate under in-vivo conditions and do not form satisfactory carrier complexes, but the antibody is still able to augment the cytotoxic action of the drug by another mechanism.

Feline large granular lymphocyte (LGL) lymphoma is an uncommon, morphologically distinct variant of feline lymphoma. Limited information exists in the literature regarding pathological and immunohistochemical descriptions, clinical fi ndings, treatment and survival times. The purpose of this study was to describe clinical features, treatment and outcome in feline LGL lymphoma. Medical records of 45 cats with LGL lymphoma were retrospectively evaluated. Decreased appetite/anorexia, weight loss, lethargy and vomiting were the most commonly reported clinical signs. All cats tested for feline leukaemia virus and feline immunodefi ciency virus infection were negative. The mesenteric lymph nodes and small intestine were the most commonly affected organs. One complete response and six partial responses were noted in the 23 cats that received chemotherapy as their initial treatment. Median survival time for cats that were treated was 57 days. Based on these results, feline LGL lymphoma appears to be minimally responsive to chemotherapy and is associated with a grave prognosis.

We report 3 cases of lymphoid neoplasms with mixed lineage features of T-, NK-, or B-cell marker expression and clonal gene rearrangement for both T-cell receptor and immunoglobulin light chain IgK. A characteristic of our cases was the lack of expression of the specific B-cell transcription factor, Pax5, which is essential for maintaining the identity and function of mature B cells during late B lymphopoiesis. In the absence of Pax5, B cells in vitro can differentiate into macrophages, dendritic cells, granulocytes, and T/NK cells. Methylation analysis of the Pax5 gene in our cases suggests that its inactivation by this epigenetic event in a committed or mature B cell, before plasma cell differentiation, may well be a common pathogenetic mechanism in mature lymphoid neoplasms with expression of multilineage antigens. In particular, case 1 may represent a mixed NK-and B-cell lineage; and cases 2 and 3 may represent mixed T and B-cell lineage, respectively. Aberrations in the DNA methylation patterns are currently recognized as a hallmark of human cancer. Cases with aberrant phenotypes require molecular analysis for lineage assignment. Studies of such cases may be helpful to better elucidate whether they represent a distinct entity with clinical, immunophenotypic, and molecular characteristics or an incidental phenomenon during malignant transformation. Interestingly, these cases were all characterized by poor clinical outcome.

a b s t r a c t B-cell lymphomas constitute the most frequent malignant neoplasm of the ocular adnexal, often presenting with localized disease. Five patients with primary localized CD20 positive B cell non Hodgkin ocular adnexal lymphomas received intralesional rituximab at the dose of 5 mg once a week for one month, followed by 10 mg weekly in case of incomplete response. Four of five patients obtained regression of symptoms and 2 of them showed complete response. No patients experienced side effects besides pain on the site of the injection. Local treatment with Rituximab for OAL is a safe and useful first-line therapeutic option.

Background Gastric carcinoma is usually characterized with significant morbidity and mortality mainly because of late presentation. Late presentation of gastric carcinoma is a prominent feature in developing and poor countries. Aim of Study The purpose of this study is to present our experience with the pattern and outcome of gastric tumors at the University of Benin Teaching Hospital, Benin City, Nigeria; with emphasis on late presentation of the patients. Patients and Methods The case files of the patients that were managed at the University of Benin Teaching Hospital for gastric tumors over a 5-year period (January 2004 to December 2006) were analyzed for biodata, symptoms and signs of disease, findings at operation, treatment offered, and outcome of treatment. Results The male/female ratio was 2.3:1, with the youngest patient being 38 years while the oldest patient was 76 years old. Upper abdominal pain and a palpable mass per abdomen were the commonest symptoms and signs, respectively. Alcohol ingestion was the commonest identifiable risk factor. Only 30.4% of the patients presented within a year of the onset of symptoms. The gastric antrum was affected in over 78% of the cases, and adenocarcinoma was found in about 90% of the patients. Partial gastrectomy with gastrojejunostomy was the commonest procedure carried out. The mortality rate was 39.1%, and of the patients that died, 66.7% occurred within a year from time of diagnosis.

The prognostic effect of weight loss prior to chemotherapy was analyzed using data from 3,047 patients enrolled in 12 chemotherapy protocols of the Eastern Cooperative Oncology Group. The frequency of weight loss ranged from 31 percent for favorable non-Hodgkin's lymphoma to 87 percent in gastric cancer. Median survival was significantly shorter in nine protocols for the patients with weight loss compared to the patients with no weight loss. Chemotherapy response rates were lower in the patients with weight loss, but only in patients with breast cancer was this difference significant. Decreasing weight was correlated with decreasing performance status except for patients with pancreatic and gastric cancer. Within performance status categories, weight loss was associated with decreased median survival. The frequency of weight loss increased with increasing number of anatomic sites involved with metastases, but within categories of anatomic involvement, weight loss was associated with decreased median survival. These observations emphasize the prognostic effect of weight loss, especially in patients with a favorable performance status or a limited anatomic involvement with tumor.

To provide an overview of what is currently known about the relationship between allergies and cancer. Data Sources: Publications were selected from a systematic review of the English-language literature from established databases (eg, MEDLINE, EBSCO) and the references of materials identified through these databases.

OBJECTIVE To evaluate the importance of inter-institutional second opinion surgical pathology review of lymphoma, and identify the lymphoma pathologic mimics. METHODS The surgical pathology material of patients referred to 2 tertiary care hospitals in the western region of Saudi Arabia (King Faisal Specialist Hospital and Research Centre and King Abdulaziz University Hospital, Jeddah, Saudi Arabia), for evaluation or therapy for lymphoma over a 10-year period (August 2001 to August 2011), were reviewed. This study included only cases in which the patient referred with a diagnosis previously made at the primary institution. RESULTS Of 560 cases, the second opinion diagnosis differed significantly from the initial diagnosis in 39 cases (7%). These include changing the diagnoses from lymphoma to non-lymphoma lesions, change the type of lymphoma with major clinical impact, and change from reactive/non-diagnostic to lymphoma. CONCLUSION Second opinion surgical pathology for lymphomas can...

The techniques of flow cytometry are becoming more and more important for the clinical hematology laboratory. No longer a novelty confined to a few specialized institutions as it was 10 years ago, flow cytometry has blossomed into a mature discipline. The methodology is well-known, the mechanical apparatus is readily available, and the role it plays in clinical hematology is increasingly appreciated. The burgeoning number of scientific articles devoted to this topic attests to the interest it has aroused as a tool for both medical research and patient care. In fact, more than a thousand such papers are now published each year and it would be impossible to deal with all the methodologies and applications of FCM currently utilized or under development. Throughout this paper four relevant hematologic fields are briefly discussed, in which FCM appears to be of great help at present: the immunophenotyping of leukemias and lymphomas, the measurement of proliferative activity and DNA ploid...

The purpose of this study was to evaluate the efficacy of adding mitoxantrone to a cyclophosphamide, doxorubicin, vincristine, L-asparaginase and prednisone containing protocol. Sixty-five dogs with multicentric lymphoma were evaluated for overall remission and survival times. Remission and survival time versus stage, substage, pretreatment hypercalcaemia and pretreatment steroid administration were also evaluated. Overall median remission for dogs with multicentric lymphoma was 302 days and overall median survival was 622 days. Of the dogs with multicentric lymphoma, 23 (35%) received all scheduled mitoxantrone doses. Only median survival versus substage was found to be significant (substage a median survival was 679 days and substage b median survival was 302 days, P = 0.025). Increasing the total combined dose of doxorubicin and mitoxantrone may improve remission times when compared with historical controls, and further studies are needed to determine how best to utilize mitoxantrone in multidrug chemotherapy protocols for canine multicentric lymphoma.

Pancreatic neoplasia in cats is rare and associated with a poor prognosis, but pancreatic nodular hyperplasia is a common incidental finding. The purpose of this study was to describe radiographic and ultrasonographic findings in cats with pancreatic neoplasia or nodular hyperplasia. Fourteen cats (age 3-18 years) were diagnosed with malignant pancreatic tumors: carcinoma/adenocarcinoma (n ¼ 11), lymphoma (n ¼ 1), squamous cell carcinoma (n ¼ 1), and lymphangiosarcoma (n ¼ 1). The most common radiographic findings were an abdominal mass or mass effect (6/6) and lack of serosal margin detail (4/6). On ultrasound, the most common finding was a focal pancreatic mass or nodule, with a size range from 0.4 cm to more than 7.0 cm (8/14). Lymphadenopathy (7/14) and abdominal effusion (7/14) were frequently seen. Five cats (age 10-16 years) with adenomatous/nodular hyperplasia had an abdominal mass or mass effect as the most common radiographic finding (3/3). On ultrasound, all cats had multiple hypoechoic nodules between 0.3 and 1.0 cm associated with the pancreas. Other common findings were pancreatic thickening (2/5), lymphadenopathy (2/5), and abdominal effusion (2/5). The only imaging finding unique to malignant pancreatic tumors was the presence of a single pancreatic nodule or mass exceeding 2 cm in at least one dimension (4/14). Although there was a tendency for neoplastic lesions to manifest as single larger lesions and for nodular hyperplasia to manifest as multiple smaller lesions, there was overlap of the imaging findings in both entities. Radiographs and ultrasound can complement but not replace cytology and histopathology in the diagnosis of feline pancreatic neoplasia.

The interplay between tumors and their immunologic microenvironment is complex and difficult to decipher, but its understanding is of seminal importance for the development of novel prognostic markers and therapeutic strategies. This chapter discusses tumor-immune interactions in several human cancers that illustrate various aspects of this complexity and proposes an integrated scheme of the impact of local immune reactions on clinical outcome. Thus, the fact that a strong infiltration of memory T cells with a Th1 and cytotoxic pattern is the strongest predictor for recurrence and metastasis is exemplified in colorectal cancer in which intratumoral chemokines shape an efficient immune reaction. Based on these data, we propose an immune score that predicts recurrence in early stage (UICC-TNM stage I-II) cancers. Studies on non-small lung cancers have confirmed findings of colorectal cancers and have addressed the question of the sites where antitumor immune reactions may take place. ...

Genetic immunization of mice with dendritic cells (DCs) engineered to express a melanoma antigen generates antigen-specific, MHC-restricted, CD4-dependent protective immune responses. We wanted to determine the role of CD4 cells and CD40 ligation of MART-1 gene-modified DC in an animal model of immunotherapy for murine melanoma. CD4 knock-out (CD4KO) or antibody-depleted mice were immunized with DC adenovirally transduced with the MART-1 gene (AdVMART1/DC) with or without CD40 cross-linking. Tumor protection was absent in CD4-depleted mice, but protection was reestablished when the CD40 receptor was engaged using three different constructs. Transduction of DCs with vectors expressing the Th1 cytokines interleukin (IL)-2, IL-7, or IL-12 could not reproduce the CD40-mediated maturation signal in this model. CD8 T-cell depletion in CD4KO mice immunized with CD40-ligated DCs abrogated the protective response. Pooled analysis of CD40 cross-linking of AdVMART1/DC administered to wild-type...

Cutaneous or subcutaneous lymphoma is one of the four different forms appearing in the horse. This type of equine lymphoma is usually lymphohistiocytic with a T, B or mixed-cell immunophenotype and with a prevalence of less than 3% among skin neoplasms. This is all about a 9-year old Warmblood mare admitted with a 5-month history of multiple cutaneous masses spreading to many parts of the body. Apart from the multiple subcutaneous nodules and plaques, which did not provide discomfort to the horse, no other abnormalities were found either in clinical or laboratory examination. Lesional histopathology and immunohistochemistry revealed a lymphohistiocytic T-cell lymphoma, which most likely was primary. The owner elected not to have her horse treated, but readmitted it for euthanasia 5 months later, because of the worsening of skin lymphoma and the appearance of general and systemic clinical signs. The ensuing postmortem was suggestive of distant metastatic disease (liver, mediastinal l...

The implementation of new techniques of imaging in the daily practice of the radiation oncologist is a major advance in these last 10 years. This allows optimizing the therapeutic intervals and locoregional control of the disease while limiting side effects. Among them, positron emission tomography (PET) offers an opportunity to the clinician to obtain data relative to the tumoral biological mechanisms, while benefiting from the morphological images of the computed tomography (CT) scan. Recently hybrid PET/CT has been developed and numerous studies aimed at optimizing its use in the planning, the evaluation of the treatment response and the prognostic value. The choice of the radiotracer (according to the type of cancer and to the studied biological mechanism) and the various methods of tumoral delineation, require a regular update to optimize the practices. We propose throughout this article, an exhaustive review of the published researches (and in process of publication) until Dec...

Lymphoma is one of the most commonly diagnosed conditions in ferrets in the United States and in Europe. Despite the high frequency of occurrence, ferret lymphoma is poorly understood and is considered to be one of the more difficult diseases to diagnose accurately and successfully treat in these animals. An update on ferret lymphoma will be provided, along with a proposal to standardize a classification system for this common disease presentation.

Non IgM-Lymphoplasmacytic Lymphoma (LPL) is a rare chronic lymph proliferative disorder with worse outcome with respect to classical LPL and Waldenstrom Macroglobulinemia. Therapeutic options are limited and differently from other indolent lymphomas no specific approved therapies are available. Here we present the case of a IgA-secreting LPL previously treated with 6 lines of therapies including immuno-chemotherapy, proteasome inhibitor and radiotherapy. At the last relapse this patient was successfully treated with zanubrutinib monotherapy within the BGB-311-AU-003 trial. Treatment with this BTK inhibitor showed to be well tolerated and led to a rapid and still ongoing response at 4 years follow up.

Objective To characterise potential fear of radiation exposure in a normal population of individuals who have volunteered to care for a radioactive family member or friend after outpatient radioimmunotherapy (RIT) treatment for cancer, and obtain their knowing and willing acceptance of the risk. Methods Over 750 carers of 300 patients confined to their homes for 1 week following outpatient iodine-131 rituximab RIT of lymphoma were interviewed by a nuclear medicine physicist according to a multi-visit integrated protocol designed to minimise radiation exposure, define risk and gain informed consent. Results Median radiation exposure of carers was 0.49 mSv (range 0.01-3.7 mSv) which is below the Western Australian regulatory limit of 5 mSv for consenting adult carers of radioactive patients. After signing a declaration of consent, only 2 carers of 750 abrogated their responsibility and none of those who carried out their duties expressed residual concerns at the end of the exit interview with respect to their radiation exposure.

Diffuse large B-cell lymphomas (DLBCLs) are phenotypically and genetically heterogeneous.
Gene-expression profiling has identified subgroups of DLBCL (activated
B-cell–like [ABC], germinal-center B-cell–like [GCB], and unclassified) according
to cell of origen that are associated with a differential response to chemotherapy
and targeted agents. We sought to extend these findings by identifying genetic
subtypes of DLBCL based on shared genomic abnormalities and to uncover therapeutic
vulnerabilities based on tumor genetics.

From a library of mouse sperm DNA, we have isolated two overlapping clones which contain the Cc, gene. One of these clones also contains the C,6 gene. The C gene is separated from the C membrane exons by approximately 2 kilobases (kb) of DNA. Ae Cc, gene was identified by (a) hybridization to poly(A) RNA prepared from the IgD-producing rat plasma cell tumor IR731, and (b) homology of a translated nucleotide sequence to the amino acid sequence of the human 8 chain. The C gene spans 8 kb of DNA in the germ line. Plasmid subclones of the Cc, gene were used as probes in Southern and RNA blot experiments. RNA blot analysis of cytoplasmic poly(A)+RNA from 1R731 and a piA+8 B-cell hybridoma revealed 1.6-and 2.7-kb 8 mRNA species with different 3' ends, which presumably encode the secreted and membrane-bound forms, respectively, of the 8 chain. Southern blot analysis of DNA from two ,u+8+ lymphomas revealed that the C5g gene is in the germ-line configuration in each case. Restriction map analysis of C and Cc, genomic clones isolated from a library of normal IA+ 8B-cell DNA also gave no evidence for DNA rearrangement in the region between the C, and Cog genes. Taken together, these data suggest that IgD expression in pI+B+ B cells does not involve a VH-to-Cs DNA switch rearrangement. We propose that simultaneous expression of CA and Cc with a single V gene is mediated by two alternative routes of RNA processing o? a primary nuclear transcript which contains the VH, C , and Cc, genes. In contrast, analogous experiments with myeloma TR731 DNA revealed that the C,, gene has been deleted from the myeloma DNA and that the Cog gene has undergone DNA rearrangement, presumably including a switch recombination of the VH gene from the C to the Cc, gene. These results indicate that two alternative meclanisms may be used in the expression of IgD molecules-RNA splicing in B cells and DNA rearrangement in plasma cells. An immunoglobulin heavy chain is composed of a variable (VH) region and one of five classes of constant (CH) region: CG (gM),

Evidence suggests a growing number of youth soccer players in the U.S. have been diagnosed with cancer (over 60 percent of which are goalkeepers). Claims have been made that the increase may be due to the crumb rubber turf and the toxic chemicals which are linked with the materials used to make the fields. This paper investigates an alternate hypothesis that the increased cancers by athletes on artificial turf fields are due to repeated electrostatic charge buildup and electrical discharge due to triboelectric effects from the crumb rubber turf and plastic blades of grass in contact with player's skin and jerseys. INTRODUCTION A soccer coach at the University of Washington [1] has developed a list of athletes with cancer who have played on synthetic turf which now stands at/above 200 athletes, 158 of whom are soccer players. Of those soccer players, 101 are goalkeepers. Eighty of the athletes on the list have some form of lymphoma.

The World Health Organization (WHO) classification of lymphomas updated in 2008 represents an international consensus for diagnosis of lymphoid neoplasms based on the recognition of distinct disease entities by applying a constellation of clinical and laboratory features. The 2008 classification has refined and clarified the definitions of well-recognized diseases, identified new entities and variants, and incorporated emerging concepts in the understanding of lymphoid neoplasms. Rather than being a theoretical scheme this classification has used data from published literature. Recent knowledge of molecular pathways has led to identification and development of new diagnostic tools, like gene expression profiling, which could complement existing technologies. However, some questions remain unresolved, such as the extent to which specific genetic or molecular alterations define certain tumors. In general, practical considerations and economics preclude a heavily molecular and genetic ...