bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of the Common Forms of Human Leukemia
Authors: MACMAHON BRIAN , CLARK DUNCAN 
Published: November 2019

Abstract
From hospital records and from death certificates, an attempt was made to assemble data on all residents of the Borough of Brooklyn diagnosed as having leukemia in the period 1943-52. A total of 1792 abstracts of hospital records and 1830 death certificates gave information on 1709 patients. The mean Brooklyn population over the same period is used to express incidences of the various forms of leukemia in relation to color, sex and age.
The incidence of leukemia in white males and females was 71.3 and 57.7 per million per annum respectively. Corresponding rates for Negroes were 46.5 and 30.6. The white-Negro difference was decreased but not eliminated by standardization to allow for differences in the age distributions of the two populations.
Sex ratios were lower for the acute forms of the disease than for the chronic forms, and, in both acute and chronic forms, for myeloid than for lymphatic cell types. No relationship of sex ratio with age at diagnosis or initial white cell count was found.
Each pathologic variety of leukemia has its own distinct age incidence curve. The lymphatic forms appear to be more sharply associated with the extremes of life than do the myeloid varieties. That is, acute lymphatic leukemia appears at a younger age than does acute myeloid leukemia and the chronic lymphatic form appears at an older average age than the chronic myeloid variety.
Mortality in Relation to Histologic Type in Hodgkin’s Disease
Authors: SMETANA HANS F. , COHEN BERNARD M. 
Published: November 2019

Abstract
1. A study of the trends of mortality in Hodgkin’s disease of diverse histologic type was undertaken with 437 cases at the AFIP Lymphatic Tumor Registry. These represent the records and pathologic material in the Registry of all white males in whom the disease was diagnosed during service in the Army in the World War II period (1941-1946).
2. Follow-up through June 30, 1953 by means of service, Veterans Administration and other records was carried out by established methods which have been demonstrated to result in virtually complete tracing.
3. On histologic analysis of the cases, 388 were confirmed as Hodgkin’s disease and these were differentiated by histologic type as Hodgkin’s granuloma (308 cases, 79 pet cent), Hodgkin’s paragranuloma (35 cases, 9 per cent) and an unspecified group (40 cases, 10 per cent) in which a decision as to type could not be made and as sarcoma (5 cases, 1 per cent). A further analysis of the 308 cases of Hodgkin’s granuloma showed secondary histologic characteristics of sclerosis in 57 instances (18.5 per cent), and of sarcoid in 13 cases (4.2 per cent).
4. The mortality at seven years after diagnosis was 77.1 per cent for the entire group of cases of confirmed Hodgkin’s disease; 28.6 per cent for Hodgkin’s paragranuloma; and 82.8 per cent for Hodgkin’s granuloma. The difference in mortality between these types is significant.
5. The seven year mortality rate for granuloma without qualifying histologic characteristics was 85.7 per cent; for cases with a sarcoid component, 81.8 per cent. The difference in mortality between nonsclerosing and sclerosing Hodgkin’s granuloma (87.5 per cent as against 74.5 per cent) was significant although the significance is borderline.
6. On re-evaluation of the 15 instances diagnosed as Hodgkin’s paragranuloma and terminating fatally, it appeared from the original biopsy material that the diagnosis probably should have been Hodgkin’s granuloma in five instances, and "malignant lymphoma, type uncertain (Hodgkin’s disease not ruled out)" in one case. In the remaining nine instances the histologic diagnosis of the original biopsy material of paragranuloma was confirmed. Autopsy material was available in three of the fifteen cases; two of these showed widespread Hodgkin’s granuloma and one presented a generalized malignant neoplasm, possibly of the Hodgkin’s sarcoma type.
7. For 95 per cent of the deaths among the histologically confirmed cases of Hodgkin’s disease the reported cause of death as found in hospital records or on death certificates was Hodgkin’s disease. It is not known for many of these whether the stated cause of death was verified by autopsy.
8. From the available evidence the question of transformation from paragranuloma to granuloma, or to sarcoma, or to any other form of lymphoma cannot be answered.
9. The correct diagnosis of the types of Hodgkin’s disease and the differentiation of secondary histologic characteristics are of importance in the evaluation of the prognosis, and for the choice of treatment.
Negative Regulation of Cell Cycle Kinetics of Human Hematopoietic Cells by the Transcription Factor Dmtf1.
Authors: Kobayashi Michihiro , Srour Edward F. 
Published: November 2019

Abstract
Hematopoietic stem cells (HSCs) are predominantly quiescent with only a small number entering active phases of cell cycle at any time point. With such tightly regulated cell cycle kinetics, HSCs ensure preservation of the stem cell pool. Many cell cycle-related proteins, mainly tumor suppressor genes, are involved in maintenance of HSCs quiescence. Dmtf1 (Cyclin D-binding Myb-like Protein1) is a transcription factor that negatively regulates cell cycle by inducing Arf expression, and its deletion has been reported in some leukemias (Bodner SM et al, 1999). As there is no information regarding the role of Dmtf1 in hematopoiesis, we examined the impact of Dmtf1 on regulating cell cycle kinetics of hematopoietic progenitor cells. Dmtf1 mRNA was expressed in human granulocytes, lymphocytes, CD34+ cells, and in murine Sca1+lin-CD117+ (KSL) cells. Using retroviral vectors (MIEG3/IRES-GFP), we first investigated cell cycle progression in 293 cells transduced with four different constructs; GFP only control vector (−), wild type Dmtf1 (WT), and two dominant negative mutants expressing a point mutation (K319E) or a deleted myb-like repeat box (dMHR). A total of 36.0% of sorted and cultured GFP+ control (−) cells were in S/G2+M 24hr after initiation of culture. Whereas 30.8% of cells expressing (WT) were in S/G2+M at the same time point, expression of the two dominant negative mutants K319E and dMHR induced 46.6% and 45.5% of the cells into S/G2+M, respectively suggesting that loss of Dmtf1 activity results in rapid cell proliferation. Interestingly, a 2.5-fold increase in the ecxpression of Arf and p21 mesured by qPCR was detected in cells transduced with WT only whereas other transduced cells did not show any change in expression of both Arf and p21. The impact of these constructs was then evaluated in cord blood cells using CFU assays. Cord blood CD34+ cells were transduced with the four vectors mentioned above and GFP+ cells were subsequently sorted and cultured. Both K319E and dMHR induced a 25% increase in the number of clonogenic progenitors relative to (−) while a modest decrease of 10% in colony numbers was detected in the WT group. Cells cycle analysis of these cells is currently under investigation. These results demonstrate that Dmtf1 acts as a negative regulator of cell cycle control in hematopoietic cells and suggests that it may play a role in the maintenance of HSC quiescence.
Low Serum Folate Levels as a Risk Factor for Non-Hodgkin’s Lymphoma.
Authors: Kim HeeNam , Shin Min-Ho , Kim Yeo-Kyeoung , Lee Il-Kwon , Yang Deok-Hwan , Lee Je-Jung , Park Kyeong-Soo , Choi Jin-Su , Kim Hyeoung Joon 
Published: November 2019

Abstract
Folate plays an essential role in cell division by participating in DNA synthesis and regenerating S-adenosylmethionine, a universal methyl donor in methylation. Folate deficiency may be involved in carcinogenesis of several type cancers through impaired synthesis and repair of DNA, or by causing global hypomethylation of DNA. So far, there is no prior report on epidemiologic data concerning the relationship between folate intake or serum folate levels and non-Hodgkin’s lymphoma (NHL) risk. We performed a case-control study (432 cases and 1,700 controls) to examine the association between serum folate levels and risk of NHL. This is, to the best of our knowledge, the first study to show that serum folate levels and risk of NHL. We also investigate whether genetic polymorphisms in folate-metabolizing enzymes interact with serum folate levels in modifying NHL risk. Serum folate was measured by ion capture assay on an AxSYM Analyzer (Abbott Diagnostics, AbbottPark, IL). The geometric mean in cases was lower than in controls (e.g., 18.9 vs 22.1 nmol/L, P < 0.001). We found a statistically significant association between serum folate level and risk of NHL, with 3.35 of odds ratios (OR) (95% confidence interval (CI), 2.27–4.95) for individuals in the lowest serum folate level category (<11.3 nmol/L [5 ng/mL]) compared with the highest category (>22.7 nmol/L [10 ng/mL]) There was a significant thymidylate synthase (TS)-folate interaction in T-cell lymphoma subtype, but we did not observe any significant gene-folate interactions in NHL and DLBCL subtype. Among subjects with low serum folate concentration (<7.5 ng/ml), the OR of T-cell lymphoma for the 3R/3R or 2R/3R genotype were 2.80 (95% CI = 1.36–5.77) and 0.78(95% CI = 0.29–2.12) for 2R/2R genotype (P = 0.045, test for homogeneity). These results provide support for the important role of folate deficiency in the risk of NHL and folate-gene interaction in the etiology of T-cell lymphoma.
Bortezomib Is Synergistic with Rituximab and Cyclophosphamide in Inducing Apoptosis of Mantle Cell Lymphoma Cells In Vitro and In Vivo.
Authors: Zhang Liang , Shi Yuankai , Han Xiaohong , Yang Jing , Qian Jianfei , Kwak Larry W. , Romaguera Jorge , Yi Qing , Wang Michael 
Published: November 2019

Abstract
Introduction: Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma with poor clinical outcome. Although frontline therapy induces a high rate of complete remission, relapse is inevitable and new regimens are needed for relapsed MCL. The proteasome inhibitor bortezomib (BTZ) induces apoptosis and sensitizes MCL cells to chemotherapy in relapsed MCL, but as a single agent, response rate is low, duration of response is short and side effects are severe. Here we evaluated whether BTZ is additive or synergistic with cyclophosphamide (CTX) and rituximab (RTX).
Material and Methods: Four human MCL cell lines SP53, MINO, Grant 519, and Jeko-1 and freshly isolated primary tumor cells from three MCL patients were treated with BTZ, CTX, RTX individually or in combination of RTX and CTX (RC), or BTZ plus RTX and CTX (BRC regimen). Cell proliferation and apoptosis were evaluated to determine if there was additive or synergistic effect of the BRC regimen. Western blot analysis was used to elucidate the molecular mechanism by which BTZ, RTX, CTX, RC and BRC induces apoptosis in MCL cells. In addition, in vivo experiments using severe combined immunodeficiency mice with human mantle cell lymphoma xenografts were performed to examine the in vivo efficacy of the regimen to control the growth of and eradicate MCL cells.
Results: BTZ and CTX as single agents inhibited the growth of MCL cell lines in a dose-dependent manner (P < 0.01). The IC50 (inhibitory concentration at 50%) for BTZ and for CTX were between 10 and 20 nM and between 5 and 20 mM, respectively. Increasing doses of BTZ with a fixed dose of RTX (10 μg/mL) and CTX (10 mM) resulted in markedly synergistic growth inhibition of MCL cells (P < 0.01). The BRC regimen induced apoptosis in about 69.7% of MCL cell lines and 92.6% of primary tumor cells (P < 0.05 and P < 0.01, compared with those induced by BTZ, RTX, CTX or RC). Furthermore, western blotting analysis showed that BRC induced apoptosis earlier via activation and cleavage of caspases-8, -9, and -3, and PARP as compared with BTZ, RTX, CTX or RC. The pan-caspase inhibitor z-VAD-FMK completely blocked apoptosis induced by BRC. In vivo studies demonstrated that BRC regimen eradicated subcutaneous tumors in MCL-bearing SCID mice and significantly prolonged the long-term event-free survival up to 10 weeks in 70% of the mice, whereas all tumor-bearing mice receiving BTZ, RTX, CTX or RC or PBS (control) died of aggressive MCL within 6 weeks.
Conclusion: Cytoreductive chemotherapy with both BTZ and anti-CD20 antibody effectively inhibited the growth and induced apoptosis of MCL cells in vitro and in vivo. Bortezomib-rituximab-cyclophosphamide (BRC) regimen may offer a better therapeutic modality for MCL patients. Thus, our data lay the basis for a clinical trial in relapsed MCL using the BRC combination treatment.
Treatment of Idiopathic Myelofibrosis Employing siRNA for Heat Shock Protein 47 (siRNA/HSP47) Encapsulated in Liposomes.
Authors: Watanabe Junichi , Matsunaga Takuya , Murase Kazuyuki , Sato Yasushi , Nagaya Taiko , Ishiwatari Hirotoshi , Takahashi Sho , Takada Koichi , Kobune Masayoshi , Shimoda Kazuya , Harada Mine , Niitsu Yoshiro 
Published: November 2019

Abstract
Idiopathic myelofibrosis (IMF) is a chronic myeloproliferative disorder characterized by bone marrow (BM) fibrosis, splenomegaly, extramedurally hematopoiesis and anemia. At present, there is no curative treatment available for this disease except allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the high therapy-related mortality of allo-HSCT, even in reduced-intensity transplantation, could not be ignored. We report a novel approach for the treatment of IMF, utilizing siRNA for a collagen specific chaperon, heat shock protein 47 (HSP47) encapsulated in liposomes (lip-siRNA/HSP47). We first confirmed suppression of HSP47 in NIH3T3 murine fibroblast cell line and primary murine BM fibroblasts, and collagen secretion from these cells by siRNA/HSP47. We next treated thrombopoietin (TPO) transgenic mice exhibiting IMF like feature (Shimoda K, Harada M et al. Leuk Res29, 761–769, 2005; Am J Hematol82, 802–806, 2007). In these mice, treatment by intravenous injection of lip-siRNA/HSP47 resulted in histological resolution of myelofibrosis associated with apoptotic death of BM fibroblasts, and improvement of anemia and splenomegaly. Thus, lip-siRNA/HSP47 therapy may be a promising treatment for IMF.
Decreased MHC-II Expression and Immune Dysfunction by Mesenchymal Stem Cells in the Bone Marrow of Patients with Myeloproliferative Disorders.
Authors: Castillo Marianne D. , Rameshwar Pranela 
Published: November 2019

Abstract
The etiology of hematological disorders has been studied at the cellular and molecular levels. These studies have led to an understanding of the effects by the bone marrow microenvironment on the pathophysiology of myeloproliferative disorders. The overarching hypothesis states that resident bone marrow Mesenchymal Stem Cells (MSCs) are important in the development of myeloproliferative disorders and are also involved in the development of fibrosis. The specific hypothesis is that MHC-II expression is decreased in patients MSCs. This makes them unable to act as antigen presenting cells and to suppress immune mediated mechanisms that lead to the development of some myeloproliferative disorders. MSCs were expanded from bone marrow aspirates of patients with AML (n=10), CML (n=10), and MDS (n=10). Flow cytometric analysis showed decreased MHC-II expression in MSCs from all patients as compared to MSCs from patients without hematological malignancy. The flow cytometry results were verified in functional studies using the MSCs as stimulators in a one way mixed lymphocyte reaction. Compared to MSCs from non-hematological malignancy patients, MSCs from study subjects showed reduced ability to elicit allogeneic responses. Retrospective analyses of bone marrow biopsies using immunohistochemistry showed an increase in the amount of MSCs in myelofibrosis patients, compared to patients without evidence of fibrosis, alluding to their role in the development of this condition. These results suggest that MSCs may be dysfunctional in patients with hematological disorders. Variations in the immune properties and the increased amount of MSCs in these patients open an avenue for a lingering question on the etiology of the development of some hematological disorders. Do dysfunctions of MSCs precede myeloproliferative disorders and leukemia or does the opposite occur? In summary, we provide insight into the immune-mediated mechanisms related to the pathophysiology of these disorders, which may have clinical implications for future therapies of bone marrow related disease.
An Analysis of Occurrence and Prognosis Related Factors of Renal Dysfunction in Patients with Multiple Myeloma.
Authors: Fu Rong , Wang Ting , Shao Zonghong 
Published: November 2019

Abstract
Objective To analysis the occurrence and prognosis related factors in renal dysfunction with multiple myeloma(MM).
Methods Seventy-four cases with MM were enrolled in this study. The risk factors of occurrence and prognosis were analyzed.
Results The incidence of renal dysfunction (RD) with MM was 56.8%, Age, hypertention, hemoglobin, serum ALB and GLO levels, serum β2MG, serum calcium and phosphonium level, the percentage of myeloma cells in bone marrow, types of MM, Durie-Salmon stage were the single factors associated with the incidence of RD with MM. Hypertention, serum β2MG and ALB levels were the multiple factors associated with the incidence of RD with MM. ALB was the protection factor and the other two were risk factors. The renal function recovered rapidly in the patients who received CR or received blood transfusion. The patients with renal dysfunction survived shorter (28±5months) than those with normal renal function (42±6months). Renal dysfunction caused more MM patients death(84.6%) in 3 months.
Conclusion Hypertention and high tumor burden were the risk factors of renal dysfunction in MM, effective chemothemapy and support treatment help renal function recovery.
Clinical Features and Management of Jaw Osteonecrosis in Patients Receiving Bisphosphonate Therapy.
Authors: Alves Fabio , Prado José D. , Rocha André C. 
Published: November 2019

Abstract
Osteonecrosis of the jaws (ONJ) in patients receiving bisphosphonates is currently being discussed in the scientific literature. Oral bisphosphonates such as alendronate are commonly used to treat osteoporosis and have rarely been associated with ONJ in the benign setting. There is a greater number of reported ONJ cases in patients using intravenous bisphosphonates such as pamidronate and zoledronic acid for cancer-related indications. Many authors have associated local factors, such as dental extraction, periodontal disease, abscesses, and other oral problems, with the development of ONJ, and some have also suggested risk factors other than dental irritation. The aim of this study was to describe the clinical data from oncology patients with ONJ from a single institution. A total of 18 ONJ cases were identified among all patients treated at or referred to our institute (Hospital do Cancer A C Camargo, Sao Paulo, Brazil). These patients had a variety of primary malignancies: breast cancer (n = 7), multiple myeloma (n = 4), prostate cancer (n = 3), lung cancer (n = 3), and renal cancer (n = 1). Current bisphosphonate therapy included zoledronic acid (n = 15; 7 [47%] had received prior pamidronate therapy), pamidronate (n = 2), and alendronate (n = 1). The ONJ cases were managed conservatively using local irrigation with 0.12% chlorhexidine gluconate, debridement, and antibiotics. A total of 29 local ONJ lesions were found: 13 patients had 1 lesion, 3 patients had 2 lesions, and 2 patients had 5 lesions. The majority (n = 16 [89%]) of the patients experienced some level of local discomfort/pain, 6 complained of halitosis, and only 2 patients were asymptomatic. Clinically, 62% of the ONJ lesions were associated with dental work and extractions; only 20% occurred spontaneously. The majority (59%) of the ONJ lesions completely healed in 9 patients. Overall, most of the ONJ lesions were associated with dental procedures, and pain was the symptom most frequently reported. Excellent dental hygiene was found to be important for preventing infections and ONJ and also to contribute to lesion healing in the majority of the cases.
Osteonecrosis of the Jaw in Multiple Myeloma Patients (the IFM Registry).
Authors: Fuzibet Jean Gabriel , Viellard Marie Hélène , Rossignol Benoit B.R. , Doyen Chantal C.D. , Hulin Cyril , Garderet Laurent L.G. , Blanc Michel M.B. , Marit Gerald , Facon Thierry T.F. , Moreau Philippe 
Published: November 2019

Abstract
PURPOSE: to describe the incidence, characteristics and risk factors for osteonecrosis of the jaw (ONJ) in multiple myeloma (MM).
PATIENTS AND METHODS : retrospective review of 51 ONJ collected from the IFM centers. For MM, age at diagnosis, isotype, DS staging, nature of chemotherapy and number of Stem-Cell Transplantation were the same that expected.
RESULTS: ONJ occurred predominantly in the mandible (70%). The median time of exposure to biphosphonates (BP) was 45 months (4 to 144 months). BP therapy included: zoledronate (85%), pamidronate (10%), clodronate (5%), all of the patients have received intravenous BP before, two patients have no BP at the time of diagnosis of ONJ.
RISK FACTORS: dental extraction (59%) other dental care (5%), dental infection (24%), others (30%), no risk factor (10%). SYMPTOMS: pain (92%), purulent discharge (37%), presence of exposed bone (60%), fracture (2%).
MANAGEMENT: BP discontinuation (84%), medical treatment (86%), removal of sequestra (51%), extensive surgery (20%).
EVOLUTION: improvement (55%), chronical symptoms (70%).
INCIDENCE: we have not the number of exposed patients but: 46 centers/73 reported no ONJ.The first report was march 2001. In the same period, 1695 patients where included in IFM trials and only 16 ONJ where observed. Year of diagnosis: before 2004: 5 cases; 2004: 11 cases; 2005:26 cases; 2006: 7 cases; 2007(6 months): 2cases.
CONCLUSION: ONJ is an adverse side effect of amino BP therapy (zoledronate>pamidronate), is time dependant and often after dental extraction. Preventive recommandations applied in 2005 can explain the decreasing incidence of ONJ in our study.