bluuebunny/crossref_metadata_2025_split huggingface dataset:
Diffuse Large B-Cell Lymphoma: Relevance of bcl-2 Expression at a National Hospital from Lima Peru 2000–2002.
Authors: Egoavil R. Cecilia M. , Delgado G. Victor M. , La Serna Jesus 
Published: October 2019

Abstract
Diffuse large B-cell lymphoma (DLCL) exhibits heterogeneous clinical features and varies in response to treatment and prognosis. Establishment of parameters that can predict outcome could help to identify patients who may benefit from risk-adjusted therapies. Because apoptosis-related proteins may play an important role in predicting the prognosis of DLCL, the current study investigated the significance of bcl-2 expression in relation to clinical characteristics in this patients. We studied 125 patients (74/51 men/women; median age 64.17 years) consecutively diagnosed with de novo DLBCL in a single institution from Peru (HNGAI) during 3-year period (2000–2002).Morphology, and clinical characteristics were analyzed according to the primary site of the lymphoma and edge. Paraffin-embedded specimens from 88 were analyzed immunohistochemically for bcl-2 protein expression. Cases with a positive immunohistological stain in more than 20% of the tumor cells were considered positive expression. Results: Sites of the disease were: lymph node, 78 cases (62.4%); Waldeyer’s ring, 18 (14.4%); and extranodal sites, 45 (36%), including GI tract in 33 cases. 5-year overall survival (OS) was 19.7%. Log-rank analyses of survival showed significant differences between ≥60 years old and younger patients (P=0.003).bcl-2 expression was identified in 34 patients (38.6%), There was no significant difference in the OS (P=0.453) between the bcl-2+ (n=34) and bcl-2− (n=54) groups. In conclusion, bcl-2 expression appeared to be non predictive of a good OS in patients with DLCL, however, there was still a clear trend that the bcl-2+ patients died sooner than the patients with tumors that contained bcl-2− lymphoma cells. The current study show all patients as were staged or confined in a group with high or high intermediate IPI scores and could be candidates for alternative therapeutic approaches.
Primary Oral Cavity Lymphomas. Features of 29 Patients Assisted at Oncology Hospital Marie Curie, Buenos Aires Argentina.
Authors: Dragosky Marta O. , Frascino Nelly , Alcaraz Susana , Annetta Isabel , Devoto Laura , Luchetta Patricia , Marquez Marisa , Giaco Carmen , Gallo Karina , Acosta Gabriela , Alcoba Elsa , Stagnaro Jorgelina , Guerrero Laura 
Published: October 2019

Abstract
Primary oral cavity lymphomas (POCV) are uncommon and must be distinguish from widespread involvement of systemic lymphomas.
Countries with high incidence of oral malignancies report cancer predominance. HIV+ population have higher prevalence than immunocompetent patientes. Alcohol and tobacco have been mentioned like risk factors. The International Prognostic Index has been taken in consideration. Patients attended Hospital on referal from medical or odontology centers and others on their own. A total of 29 patientes were studied. Aged 21 to 70, media 47,3 years. Male predominance: 69%. Histopathology: NHL high grade B: 19 cases, NHL low grade B: 4, NHL high grade T: 3 and plasmoblastic 3. Sites: superior maxilla: 12, inferior maxilla 11, tongue 3, palate 3. No predominance for right or left locations. HIV+ 9 patients (31%) The prevalence among inmmunocompetent was markedly lower: in 662 diagnosed with NHL 20 cases=3,02%, in 32 NHL HIV+ 9 cases= 28,12%. More frequent complaints were: painless swell of the maxilla, movable teeth, dysphagia, facial edema. The stages were I and II, 28% with locoregional extension: adenopathies or bone infiltration. The IPI was 0 in17, 1 in 10 and 2 in 2 patients. All patients received chemotherapy (CVP, CHOP), with initial good response and early relapse in HIV+.
Conclusions: In correspondence with others reports, we found predominance in male and middle age, B cell lineage and connection with HIV infection. POCL may lead to the diagnosis of an up to then unknown HIV infection. The little specificity of the initial symptons tends to delay the diagnosis and the referal to a specialized center. IPI didn’t prove useful as a prognostic assessment.
Effects of Integrin α5β1-Mediated Signal TransductionPathways on the Proliferation and Apoptosis of K562 and CML Cells.
Authors: Pan Ling , Niu Zhiyun , Zhang Xuejun , Wang Fuxu , Suo Xiaohui , Dong Zuoren 
Published: October 2019

Abstract
Objective and methods: More than 90% of chronic myeloid leukemia (CML) patients have the Philadelphia (Ph) chromosome which produces a specific oncoprotein known as BCR/ABL (P210 protein). Having strong tyrosine kinase activity, the BCR/ABL oncoprotein can trigger several signal transduction pathways and inhibit the normal signal transduction pathways of CML progenitor cells. Presenting on cell surface, Integrins belong to the adhesive molecule family. They mediate adhesion of cell to cell or cell to extra cellular matrix (ECM) and take part in many physiological and pathological processes such as signaling transduction, cell differentiation, proliferation and apoptosis. Many studies showed that abnormal circulating of CML Ph+ cells in peripheral blood and unregulated proliferation of CML Ph+ cells in bone marrow were related closely to the abnormal adhesion function of integrins. It is also well known that Interferon (IFN)-α is one of the effective therapeutic agents for CML. Therefore the present study was designed, by cell culture, FCM, RT-PCR and Western Blot, to observe the effects of IFNα-2b on the proliferation of k562 cells and fresh leukemia cells from patients with CML-in blast crisis (CML cells), before and after integrin α5β1 having been neutralized by Anti-integrin α5β1 monoclonal antibody (Anti-α5β1), and to investigate the changes of mRNA and protein of several key molecules in integrin-mediated pathways, such as FAK, ERK, AKT, PI3K and Cychin D1, p21 and survivin before and after the treatment of Anti-α5β1 with or without IFNα-2b.
Results: The expression level of integrin α5β1 on K562 cells and CML cells was much higher than that on health volunteers’ BMMNC. And the adhesion capability of K562 cells and CML cells to fibronectin (FN) decreased significantly than that of health volunteers’ BMMNC. IFNα-2b improved the adhesion capability of K562 cells and CML cells to FN. Anti-α5β1 inhibited proliferation but induced apoptosis and G0/G1 arresting of K562 cells and CML cells. Anti-α5β1 downregulated the expression level of p-FAK-, p-ERK-, PI3K- and p-AKT-mRNA and protein. Anti-α5β1 also downregulated the expression level of Cyclin D1 mRNA, but upregulated the expression level of P21 mRNA. Moreover, the effect of Anti-α5β1 is stronger than that of IFNα-2b.
Conclusions: Anti-α5β1 inhibited integrin α5β1-mediated signal transduction pathways: FAK-ras-ERK pathway and PI3K-AKT-survivin pathway. This might be the mechanisms of Anti-α5β1 inhibiting proliferation and inducing apoptosis of K562 cellsand CML cells. This indicated that the dysfunction of integrin α5β1 pathway might have important meanings in the leukemogenesis of CML and might become a new target for the treatment of CM.
Blockage of IL-6 Mediated JAK2/STAT3 Cell Signaling Pathway by sIL-6R Effectively Inhibited the Growth of Multiple Myeloma Cell.
Authors: Park Ju-won , Ahn Kwang-Sung , Kim Young-Ju , Bae Eunkyung , Lee Yong-Yeol , Yoon Sung-Soo , Kim Inho , Park Seonyang , Kim Byoung-Kook 
Published: October 2019

Abstract
Interleukin-6 (IL-6) is a key growth factor and thus plays a pivotal role in the pathogenesis of multiple myeloma. IL-6 is absolutely necessary for the cellular signalling cascade via JAK/STAT and RAS/MAPK pathways involved in proliferation and viability. We found interleukin (IL)-6 induced JAK-2 phosphorylation and induced proliferation of multiple myeloma cell line. Also phosphorylation of Stat1 and Stat3 was increased by IL-6 stimulation. Silencing JAK2 expression by small interfering RNA (siRNA) abrogated IL-6 induced phosphorylation of STAT3. In addition, soluble interleukin-6 receptor (sIL-6R) antagonized the function of hIL-6 and efficiently induced the growth arrest and apoptosis of U266 cells in a dose-dependent manner. Increasing levels of sIL-6R suppressed the phosphorylation of JAK-2 and Stat3. This suggests a comprehensive knowledge of the signaling and survival pathways could help find additional molecular targets and lead to the development of novel and more effective treatment strategies in multiple myeloma.
Treatment of Diuretic Refractory Pleural Effusions with Bevacizumab in Four Patients with Primary Systemic Amyloidosis (AL).
Authors: Hoyer Robert J. , Leung Nelson , Witzig Thomas E. , Lacy Martha Q. 
Published: October 2019

Abstract
Introduction
Refractory pleural effusions present a challenging management problem and are associated with a poor prognosis in patients with primary systemic amyloidosis (AL). Vascular endothelial growth factor (VEGF) has been implicated to play a role in both malignant and non-malignant pleural effusions through its ability to regulate vascular permeability. VEGF can induce morphologic changes in vascular endothelial cells, regulate gene expression, stimulate cell proliferation and migration, and inhibit apoptosis. We report a series of four patients with AL who presented with bilateral pleural effusions that were refractory to diuretic therapy. After treatment with bevacizumab, an anti-VEGF antibody, three of the four patients had improvement in their pleural effusions, peripheral edema, and functional status.
Methods
A retrospective chart review was conducted four patients with AL and refractory pleural effusions who received bevacizumab. Three of the patients had documented renal amyloid by biopsy and two had suspected cardiac involvement. Serum creatinine ranged from 1.3–3.8 mg/dL (mean=2.15 mg/dL), 24 hour urine protein ranged from 190 mg – 12.5 grams per 24 hours (mean=6.1 grams). Bevacizumab 5 mg/kg was administered for 1–4 cycles (mean=2).
Results
Three of the four patients had demonstrable improvement in their pleural effusions, peripheral edema and functional status after a single dose of bevacizumab. One patient had no objective response to treatment. The three responders experienced a 2–7 kg (mean= 4.6 kg) decrease in weight within two weeks after receiving bevacizumab. This effect was observed in patients who were re-treated. All three patients received concurrent diuretic therapy, however, they had not previously responded to diuretic therapy. Two weeks after the first dose of bevacizumab, the 24 hour urine protein of the patient who received four cycles of bevacizumab increased to 18.2 grams per 24 hours, however it returned to baseline (12.5 grams per 24 hours) one week later, and increased slightly to 13.3 grams per 24 hours after the fourth dose. A second patient also experienced an increase in 24 hour protein excretion (6.9 grams per 24 hours to 9.2 grams per 24 hours) after the first dose of bevacizumab. One patient experienced a deep vein thrombosis after the third cycle of bevacizumab. No hemorrhagic complications were observed.
Conclusion
Bevacizumab may represent a novel non-invasive management strategy for patients with systemic amyloidosis and diuretic-refractory pleural effusions, however, additional studies are needed to further define the role of bevacizumab in the management of this group of patients.
Myeloablative Conditioning Followed by T-Cell Depletion Is Associated with Low Treatment Related Mortality.
Authors: Novitzky Nicolas , Thomas Valda , Toit Cecile du , McDonald Andrew 
Published: October 2019

Abstract
Introduction: Classically the conditioning for transplantation in haematological malignancies has been with myeloablative doses of radiation or chemotherapy, and was followed by variable immunosuppression for the prevention of GvHD. This strategy has been associated with substantial transplant related mortality from regimen toxicity and GvHD, which were most pronounced in older patients. Reduced intensity conditioning programs that are mainly immunosuppressive allow engraftment and predisposed to donor chimerism and appear to have lower TRM, but seem associated to higher rates of GvHD and disease recurrence. To better apportion conditioning strategies for patients undergoing allogeneic stem cell transplantation, we studied the outcome of 81 patients who received similar GvHD prophylaxis with T-cell depletion and immunosuppression, after myeloablative conditioning.
Patients & methods: Patients with haematological malignancies, in remission or still responsive to chemotherapy who had an HLA identical sibling were offered T-cell depleted stem cell grafts. Conditioning was with ablative doses of either chemotherapy or total body radiotherapy. Stem cells were mobilised into the blood (PBPC) with G-CSF (5–10ug/kg × 5) and grafts were harvested by large volume (30 litres) apheresis. GvHD prophylaxis was by ex vivo depletion of lymphocytes from the graft with CAMPATH-1 H antibodies followed by therapeutic doses of cyclosporin until day 90. End points were TRM, disease recurrence rate and overall survival time.
Results: 90 consecutive patients with median age of 45 (17–62) years were studied. The diagnosis included acute leukaemia (ALL in 7) in CR in 38, myeloproliferative disorders in 16, lymphoproliferative diseases in 26 and multiple myeloma in 10. Post transplantation, patients with CML received, in addition, escalating doses of lymphocytes at 6 months (maximum 1 × 107/kg CD3) or imatinib for 12 months. Median CD34+ cell number was 2.7 (1–12.3) and the median dose of campath-1H was 10 (range 7.5–45) mg. Median time to engraftment was 11 days. Overall, 20 (22%) individuals died while treatment related mortality occurred in 17% (n= 15; VOD 3, infections in 8, pneumonitis in 1, EBV lymphoma in 1 and GvHD in 2). GvHD (> grade1) occurred in 7 patients, was controlled with further immunosuppression but lead to death from infections in 6. Disease recurrence was seen in 12, but 7 with CML or myeloma responded to DLI. At a median follow up of 688 days, 77 survive; 75% in unsustained remission.
Conclusions: Myeloablative conditioning is well tolerated in patients receiving T-cell depleted grafts, and treatment related mortality of <20% can be expected consistently with this strategy. This information is useful to more precisely select patients who would benefit most from reduced intensity conditioning schedules.
Experiences with Caspofungin Plus Posaconazole in Immunocompromised Adults with Invasive Aspergillosis (IA) Refractory to Prior Standard Therapy.
Authors: Dahlke Joachim , Zabelina Tatjana , Lellek Heinrich , Muth Alexander , Waschke Olga , Wolschke Christine , Sobottka Ingo , Kroeger Nicolaus , Zander Axel R. 
Published: October 2019

Abstract
Background: Aspergillosis is a lethal infection of immunocompromised patients that respond poorly to antifungal therapy. Caspofungin (CAS) or Posaconazole (POS) as salvage monotherapy for IA have response rates of 45% and 42% respectively. Preliminary results of in vitro studies, animal models and clinical studies suggest that combination therapy with azoles and echinocandins may have additive activity against Aspergillus species.
Methods: Seven adult patients after unrelated haematopoietic stem cell transplantation, with proven, probable or possible IA (per EORTC/MSG criteria) and refractory to standard antifungal therapy received Caspofungin plus Posaconazole (standard monotherapy dosage). All patients had > 3 days of combination antifungal therapy. Underlying diseases were AML (n=5), Biphenotypic leukaemia (n=1), Mantle cell Lymphoma (n=1). Three patients were neutropenic (ANC<500), all patients received immunosuppressive medication. IA sites were lung (n=6) and liver (n=1). All patients were evaluable for toxicity. Efficacy was assessed by signs, symptoms and CT-scan/ultrasound. Favourable responses (complete or partial) required significant clinical and radiographic/ultrasound improvement.
Results: Success at end of combination therapy (EOCT) was seen in six patients (86%). One critically ill patient died (due to bacterial sepsis and severe acute GvHD) four days after first administration of combination therapy. One patient with complete radiographic response died 20 days after EOCT due to bacterial sepsis in relapse of AML. Combination therapy at 4 to 59 (mean 35.7) days was well tolerated. No patient discontinued combination therapy due to toxicity. Follow up from start of combination therapy was 4 to 204 (mean 79.8) days.
Conclusion: Randomized trials are warranted to determine whether this combination should be used as primary therapy for aspergillosis.
Favorable Impact of Short Term Methotrexate on Early Immune Reaction and Non-Relapse Mortality in Umbilical Cord Blood Transplantation for Adult Patients.
Authors: Watanabe Masato , Narimatsu Hiroto , Terakura Seitaro , Matsuo Keitaro , Oba Taku , Kasai Masanobu , Iida Hiroatsu , Hamaguchi Motohiro , Kohno Akio , Murata Makoto , Sawa Masashi , Miyamura Koichi , Morishita Yoshihisa ,   Nagoya BMT Group
Published: October 2019

Abstract
Cord blood transplantation (CBT) represents an attractive alternative for patients with advanced hematological malignancy who lack matched related or unrelated donors. Adult patients receiving myeloablative or reduced-intensity CBT display a 90% chance of engraftment, but also experience a 50% rate of transplant-related mortality. Post-transplant immune disorders including early immune reactions and acute GVHD are problematic in CBT for adult patients. These reactions and/or additional immunosuppressive therapy might increase the risk of infection and organ dysfunction, leading to high rates of transplantation-related mortality. However, optimal prophylaxis and management for immune reactions have not been established in CBT. We investigated retrospectively whether intensive graft-versus-host disease (GVHD) prophylaxis has a prognostic impact on CBT. Post-CBT immune reactions were classified according to time course as pre-engraftment immune reaction (PIR), engraftment syndrome (ES) or acute GVHD. Between March 2001 and September 2003, a total of 77 patients underwent CBT at 8 centers of the Nagoya Blood and Marrow Transplantation Group (NBMTG). Median age of patients was 48 years (range, 18–69 years). Preparative regimens were myeloablative (n=31) or reduced-intensity (n=46). Acute GVHD prophylaxis included cyclosporine alone (n=23), tacrolimus alone (n=12), cyclosporine plus short-term methotrexate (n=17), tacrolimus plus short-term MTX (n=23) or cyclosporine plus methylprednisolone (n=2). Cumulative incidences of PIR, ES and grade I-IV GVHD were 38%, 12% and 29%, respectively. Short-term MTX exerted significant favorable effects on PIR in univariate analysis (hazard ratio, 0.41; 95% confidence interval, 0.19–0.89) and on non-relapse mortality (NRM) in multivariate analysis (hazard ratio, 0.36; 95% confidence interval, 0.16–0.81). On the other hand, PIR occurred in 35% of patients with cyclosporine and 37% with tacrolimus. Short-term MTX appears to offer optimal GVHD prophylaxis to reduce PIR and improve NRM.
Figure Figure
Oral Tipifarnib (R115777) Has Single Agent Anti-Tumor Activity in Patients with Relapsed Aggressive Non-Hodgkin Lymphoma (NHL): Results of a Phase II Trial in the University of Iowa/Mayo Clinic Lymphoma SPORE (CA97274).
Authors: Witzig Thomas E. , Maurer Matthew J. , Johnston Patrick B. , Colgan Joseph P. , Kaufmann Scott H. , Inwards David J. , Micallef Ivana N. , Ansell Stephen M. , Zent Clive S. , Allmer Cristine , Weiner George J. , Wooldridge James E. , Link Brian K. , Habermann Thomas M. 
Published: October 2019

Abstract
Background: Patients (pts) with aggressive NHL who relapse after conventional chemotherapy or stem cell transplant have a poor prognosis. Novel agents are needed for this important subset. Tipifarnib is an orally available methylquinolone derivative that is an inhibitor of the farnesyl transferase enzyme that transfers the farnesyl group from farnesyl pyrophosphate to specific polypeptides including small GTPases of the Ras, Rho-B, and Rheb families, as well as nuclear lamins and kinetochore proteins. Tipifarnib has documented activity in acute leukemia and produces stable disease in relapsed multiple myeloma. The goal of this study was to evaluate the activity of single-agent tipifarnib in patients with relapsed aggressive NHL in the context of a phase II trial.
Methods: Pts with relapsed diffuse large, follicular grade III, or mantle cell lymphoma were eligible for this study. Pts were treated with oral tipifarnib 300 mg twice daily d1–21 q 28 days until progression. Pts were restaged after 2 cycles, 6 cycles, and every 3 cycles thereafter. Tumor was sampled prior to tipifarnib and at day 8 in selected patients with accessible tumors. These paired samples were assayed for accumulation of unprocessed HDJ-2 and prelamin A, two polypeptides that require farnesylation for processing.
Results: Forty-two pts were accrued between March 2004 and June 2006. Thirty-seven pts had diffuse large cell, 1 follicular grade III, and 4 had mantle cell. Of the 38 patients evaluable for response, 7 (18%) had a partial response and 8 (21%) had stable disease. The 7 responders all had diffuse large cell histology. Median progression-free survival (PFS) for all pts was 2 months (range, 0–25+). The PFS of the 7 responders was noteworthy at 4.2, 4.9+, 6.7, 9.6, 14.9+, 21.6+, and 25.1+ months, respectively. The primary toxicity was myelosuppression and 33% of pts required dose reductions. The median dose received in all pts was 300 mg twice daily (mean 275, range, 100–400). The median dose received by the 7 responders was 200 mg twice daily (range, 100–400). The dose of 300 mg twice daily resulted in accumulation of unfarnesylated forms of one or both markers in all pts studied to date.
Conclusion: Oral tipifarnib has antitumor activity as a single agent with an excellent toxicity profile in pts with relapsed/refractory aggressive lymphoma. When given in this dose and schedule, tipifarnib is well-tolerated and can be taken for months without cumulative toxicity. This drug warrants further investigation in combination with conventional chemotherapy and other novel agents for the treatment of this important subset of patients.