Total body irradiation in a case of thalassemia major with source to axis distance based planning: A case report

Background: The use of total body radiation (TBI) before hematopoietic stem cell transplantation (HSCT) would increase the engraftment without transplant-related morbidity or mortality among Thalassemia major (TM) cases. Case presentation: A 2-year-old female child, diagnosed with TM was scheduled for haploidentical allogenic transplant-based protocol, and after that, based on protocol she was scheduled to undergo a single session of TBI as a conditioning regimen before haploidentical allogenic hematopoietic stem cell tranplant. A total dose of 4 Gy was administered.. The incidence of graft failure was reduced as TBI was used before allogeneic stem cell transplantation. TBI provided a uniform dose of radiation to the entire body, penetrating areas such as the central nervous system (CNS) and testes. Conclusion: Total Body Irradiation with the SAD technique is the most effective way of treatment. As it is comfortable for the patient to undergo, easily reproducible, and it helps to achieve a uniform dose distribution

Total body irradiation in a case of thalassemia major with source to axis distance based planning: A case report

Background: The use of total body radiation (TBI) before hematopoietic stem cell transplantation (HSCT) would increase the engraftment without transplant-related morbidity or mortality among Thalassemia major (TM) cases. Case presentation: A 2-year-old female child, diagnosed with TM was scheduled for haploidentical allogenic transplant-based protocol, and after that, based on protocol she was scheduled to undergo a single session of TBI as a conditioning regimen before haploidentical allogenic hematopoietic stem cell tranplant. A total dose of 4 Gy was administered.. The incidence of graft failure was reduced as TBI was used before allogeneic stem cell transplantation. TBI provided a uniform dose of radiation to the entire body, penetrating areas such as the central nervous system (CNS) and testes. Conclusion: Total Body Irradiation with the SAD technique is the most effective way of treatment. As it is comfortable for the patient to undergo, easily reproducible, and it helps to achieve a uniform dose distribution

Antioxidant efficacy of Litchi (Litchi chinensis Sonn.) pericarp extract in sheep meat nuggets.

Not AvailableIn the present study, the efficacy of litchi fruit pericarp (LFP) extract (0.5%, 1.0% and 1.5% concentration) in retarding lipid oxidation of cooked sheep meat nuggets was evaluated and compared to butylated hydroxyl toluene (BHT, 100 ppm). The total phenolic content and antioxidant potential of LFP extracts were determined. The thiobarbituric acid reactive substance (TBARS) values were evaluated to assess the potential of LFP extracts as natural antioxidants for oxidative stability of cooked nuggets during 12 days of refrigerated storage. Results show that total phenolics content in 10 mg LFP powder was comparable to 100 ppm BHT, but 15 mg LFP powder had significantly higher (p < 0.05) total phenolics content and reducing power than the synthetic antioxidant. LFP extract did not affect pH, cooking yield and the sensory attributes of cooked nuggets. Non-treated control and nuggets with 1.0% LFP extract had significantly lower total phenolics than nuggets with 1.5% extract and BHT. TBARS values were significantly lower (p < 0.05) throughout the storage period in cooked meat nuggets containing either LFP extract or BHT than in non-treated control. Results indicate that LFP extracts are promising sources of natural antioxidants and can potentially be used as functional food additives in meat products at 1.5% without affecting products’ acceptability.Not Availabl

Poly(ADP-ribose) polymerase family member 14 (PARP14) is a novel effector of the JNK2-dependent pro-survival signal in multiple myeloma

Copyright @ 2013 Macmillan Publishers Limited. This is the author's accepted manuscript. The final published article is available from the link below.Regulation of cell survival is a key part of the pathogenesis of multiple myeloma (MM). Jun N-terminal kinase (JNK) signaling has been implicated in MM pathogenesis, but its function is unclear. To elucidate the role of JNK in MM, we evaluated the specific functions of the two major JNK proteins, JNK1 and JNK2. We show here that JNK2 is constitutively activated in a panel of MM cell lines and primary tumors. Using loss-of-function studies, we demonstrate that JNK2 is required for the survival of myeloma cells and constitutively suppresses JNK1-mediated apoptosis by affecting expression of poly(ADP-ribose) polymerase (PARP)14, a key regulator of B-cell survival. Strikingly, we found that PARP14 is highly expressed in myeloma plasma cells and associated with disease progression and poor survival. Overexpression of PARP14 completely rescued myeloma cells from apoptosis induced by JNK2 knockdown, indicating that PARP14 is critically involved in JNK2-dependent survival. Mechanistically, PARP14 was found to promote the survival of myeloma cells by binding and inhibiting JNK1. Moreover, inhibition of PARP14 enhances the sensitization of MM cells to anti-myeloma agents. Our findings reveal a novel regulatory pathway in myeloma cells through which JNK2 signals cell survival via PARP14, and identify PARP14 as a potential therapeutic target in myeloma.Kay Kendall Leukemia Fund, NIH, Cancer Research UK, Italian Association for Cancer Research and the Foundation for Liver Research

Galectin-3C Inhibits Tumor Growth and Increases the Anticancer Activity of Bortezomib in a Murine Model of Human Multiple Myeloma

Galectin-3 is a human lectin involved in many cellular processes including differentiation, apoptosis, angiogenesis, neoplastic transformation, and metastasis. We evaluated galectin-3C, an N-terminally truncated form of galectin-3 that is thought to act as a dominant negative inhibitor, as a potential treatment for multiple myeloma (MM). Galectin-3 was expressed at varying levels by all 9 human MM cell lines tested. In vitro galectin-3C exhibited modest anti-proliferative effects on MM cells and inhibited chemotaxis and invasion of U266 MM cells induced by stromal cell-derived factor (SDF)-1α. Galectin-3C facilitated the anticancer activity of bortezomib, a proteasome inhibitor approved by the FDA for MM treatment. Galectin-3C and bortezomib also synergistically inhibited MM-induced angiogenesis activity in vitro. Delivery of galectin-3C intravenously via an osmotic pump in a subcutaneous U266 cell NOD/SCID mouse model of MM significantly inhibited tumor growth. The average tumor volume of bortezomib-treated animals was 19.6% and of galectin-3C treated animals was 13.5% of the average volume of the untreated controls at day 35. The maximal effect was obtained with the combination of galectin-3C with bortezomib that afforded a reduction of 94% in the mean tumor volume compared to the untreated controls at day 35. In conclusion, this is the first study to show that inhibition of galectin-3 is efficacious in a murine model of human MM. Our results demonstrated that galectin-3C alone was efficacious in a xenograft mouse model of human MM, and that it enhanced the anti-tumor activity of bortezomib in vitro and in vivo. These data provide the rationale for continued testing of galectin-3C towards initiation of clinical trials for treatment of MM

Effects of IL-8 up-regulation on cell survival and osteoclastogenesis in multiple myeloma

[EN]IL-8 promotes cancer cell growth, survival, angiogenesis, and metastasis in several tumors. Herein, we investigated the sources of IL-8 production in multiple myeloma (MM) and its potential roles in MM pathogenesis. We found that bone marrow cells from patients with MM secreted higher amounts of IL-8 than healthy donors. IL-8 production was detected in cultures of CD138+ plasma cells and CD138(-) cells isolated from bone marrows of MM patients, and in three of seven human myeloma cell lines (HMCLs) analyzed. Interactions between MM and stromal cells increased IL-8 secretion by stromal cells through cell-cell adhesion and soluble factors. Interestingly, 1L8 expression also increased in HMCLs, stromal cells, and osteoclasts after treatment with the antimyeloma drugs melphalan and bortezomib. In fact, the effect of bortezomib on IL-8 production was higher than that exerted by stromal-MM cell interactions. Addition of exogenous IL-8 did not affect growth of HMCLs, although it protected cells from death induced by serum starvation through a caspase-independent mechanism. Furthermore, IL-8 induced by stromal-MM cell interactions strongly contributed to osteoclast formation in vitro, because osteoclastogenesis was markedly reduced by IL-8 specific neutralizing antibodies. In conclusion, our results implicate IL-8 in myeloma bone disease and point to the potential utility of an anti IL-8 therapy to prevent unwanted effects of IL-8 up-regulation on survival, angiogenesis, and osteolysis in MM.Spanish RTICC, Spanish Association against Cancer (AECC), the INNOCAMPUS Program , Spanish ISCIII-FIS (PI12/02591) and FEDER, Regional Council from Castilla y León (Consejería de Educación) and the Network of Centers for Regenerative Medicine and Cellular Therapy from Castilla y León

The use of murine models for studying mechanistic insights of genomic instability in multiple myeloma

Multiple myeloma (MM) is a B-cell malignancy characterized by the accumulation of clonal plasma cells in the bone marrow. In normal plasma cell development, cells undergo programmed DNA breaks and translocations, a process necessary for generation of a wide repertoire of antigen-specific antibodies. This process also makes them vulnerable for the acquisition of chromosomal defects. Well-known examples of these aberrations, already seen at time of MM diagnosis, are hyperdiploidy or the translocations involving the immunoglobulin heavy chain. Over the recent years, however, novel aspects concerning genomic instability and its role in tumor development, disease progression and nascence of refractory disease were identified. As such, genomic instability is becoming a very relevant research topic with the potential identification of novel disease pathways. In this review, we aim to describe recent studies involving murine MM models focusing on the deregulation of processes implicated in genomic instability and their clinical impact. More specifically, we will discuss chromosomal instability, DNA damage and repair responses, development of drug resistance, and recent insights into the study of clonal hierarchy using different murine MM models. Lastly, we will discuss the importance and the use of murine MM models in the pre-clinical evaluation of promising novel therapeutic agents