- Long-term renal function and hypertension in adult survivors of childhood sarcoma: Single center experience. [Journal Article]
- PHPediatr Hematol Oncol 2018 Sep 19; :1-10
- CONCLUSIONS: In our series of adult survivors treated for a diagnosis of sarcoma in their childhood, the prevalence of CKD was 10%. We found survivors treated with ifosfamide as the only nephrotoxic agent did not present glomerular or tubular toxicity at long term follow-up, but further studies including a larger number of cases are required to confirm it.
- Nucleosides block AICAR-stimulated activation of AMPK in skeletal muscle and cancer cells. [Journal Article]
- AJAm J Physiol Cell Physiol 2018 Sep 19
- AMP-activated kinase (AMPK) is a major regulator of energy metabolism and a promising target for development of new treatments for type 2 diabetes and cancer. 5-aminoimidazole-4-carboxamide-1-β-D-rib...
AMP-activated kinase (AMPK) is a major regulator of energy metabolism and a promising target for development of new treatments for type 2 diabetes and cancer. 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), an adenosine analogue, is a standard positive control for AMPK activation in cell-based assays. Some broadly used cell culture media, such as MEMα, contain high concentrations of adenosine and other nucleosides. We determined whether such media alter AICAR action in skeletal muscle and cancer cells. In nucleoside-free media, AICAR stimulated AMPK activation, increased glucose uptake and suppressed cell proliferation. Conversely, these effects were blunted or completely blocked in MEMα that contains nucleosides. Addition of adenosine or 2'-deoxyadenosine to nucleoside-free media also suppressed AICAR action. MEMα with nucleosides blocked AICAR-stimulated AMPK activation even in the presence of methotrexate, which normally markedly enhances AICAR action by reducing its intracellular clearance. Other common media components, such as vitamin B12, vitamin C and α-lipoic acid, had a minor modulatory effect on AICAR action. Our findings show that nucleoside-containing media, commonly used in AMPK research, block action of the most widely used pharmacological AMPK activator AICAR. Results of cell-based assays in which AICAR is used for AMPK activation therefore critically depend on media formulation. Furthermore, our findings highlight a role for extracellular nucleosides and nucleoside transporters in regulation of AMPK activation.
- Successful treatment of refractory juvenile generalized pustular psoriasis with secukinumab monotherapy: A case report and review of published work. [Journal Article]
- JDJ Dermatol 2018 Sep 19
- Juvenile generalized pustular psoriasis (GPP) is rare and often resistant to conventional systemic therapy such as methotrexate, retinoic acid and cyclosporin A. GPP can be induced by deficiency of i...
Juvenile generalized pustular psoriasis (GPP) is rare and often resistant to conventional systemic therapy such as methotrexate, retinoic acid and cyclosporin A. GPP can be induced by deficiency of interleukin (IL)-36 receptor antagonist (DITRA). No standardized guidelines are available for juvenile GPP or DITRA, and a uniformly safe and effective biologic agent has not been identified. However, multiple biologics approved for use in plaque-type psoriasis have also been used in GPP. Herein, we report a case of a 6-year-old Taiwanese boy with GPP and homozygous mutation at c.115+6T>C within the IL-36 receptor antagonist (IL36RN) gene, who was treated successfully with secukinumab after failure of prior methotrexate, acitretin, cyclosporin A, etanercept and adalimumab. Similar to two previously reported non-adult cases of GPP successfully treated with secukinumab, our case also demonstrated a history of repeated treatment failures with several conventional oral systemic agents and biologics. Different from these two cases, however, ours is the first of juvenile GPP successfully treated with secukinumab monotherapy, without using other systemic agent concurrently during the use of secukinumab.
- A Case of Bing-Neel Syndrome Successfully Treated with Ibrutinib. [Journal Article]
- CRCase Rep Hematol 2018; 2018:8573105
- Bing-Neel syndrome is a rare manifestation of Waldenström macroglobulinemia characterized by lymphoplasmacytic cells' infiltration into the central nervous system. We present a case of a 74-year-old ...
Bing-Neel syndrome is a rare manifestation of Waldenström macroglobulinemia characterized by lymphoplasmacytic cells' infiltration into the central nervous system. We present a case of a 74-year-old patient with a known diagnosis of Waldenström macroglobulinemia and newly depressed consciousness. Flow cytology of his cerebral spinal fluid demonstrated a lambda light chain-restricted population of B-cells consistent with a CD5+ CD10+ B-cell lymphoma. Magnetic resonance imaging suggested involvement of the left optic nerve sheath and the bilateral orbital and parietal parenchyma and leptomeninges. He was diagnosed with Bing-Neel syndrome and treated with intrathecal liposomal cytarabine, intravenous high-dose methotrexate, and rituximab without improvement. Subsequently, he started treatment with ibrutinib 560 mg daily and concurrent rituximab. Within three months, he showed clinical and radiologic improvement. The patient has continued on ibrutinib and has now been stable for over 36 months. This represents the longest reported period of successful treatment of Bing-Neel syndrome with ibrutinib.
- Effects of a 15-month anti-TNF-α treatment on plasma levels of glycosaminoglycans in women with rheumatoid arthritis. [Journal Article]
- ARArthritis Res Ther 2018 Sep 18; 20(1):211
- CONCLUSIONS: Our results suggest that anti-TNF-α therapy has a beneficial effect on extracellular matrix remodeling in the course of RA.
- Successful Treatment of a Recurrent Cesarean Scar Pregnancy by Transvaginal Cesarean Scar Pregnancy Lesion Resection: A Case Report. [Journal Article]
- JRJ Reprod Med 2016 Nov-Dec; 61(11-12):595-7
- CONCLUSIONS: This case highlights the likelihood of RCSP and the need for transvaginal CSP lesion resection to decrease the risk of RCSP in CSP patients who desire future pregnancy.
- Successful Treatment of a Pararenal Pregnancy Using High-Dose Methotrexate Regimen: A Case Report. [Journal Article]
- JRJ Reprod Med 2016 Nov-Dec; 61(11-12):592-4
- CONCLUSIONS: The site of an ectopic pregnancy should be sought thoroughly to avoid missing an abdominal pregnancy and hence disastrous hemoperitoneum. While medical therapy with high-dose methotrexate is not a standard treatment, it can be considered after failing the traditional therapy, provided that there is adequate treatment monitoring and expertise in handling the side effects of the medication.
- Circadian rhythms and rheumatoid arthritis. [Journal Article]
- JBJoint Bone Spine 2018 Sep 15
- Circadian rhythms (Nobel prize for Medicine 2017) regulate, under action of biological clocks located both at the level of central nervous system and inside peripheral cells, several daily activities...
Circadian rhythms (Nobel prize for Medicine 2017) regulate, under action of biological clocks located both at the level of central nervous system and inside peripheral cells, several daily activities, embracing sleep, feeding times, energy metabolism, endocrine and immune functions with related pathological conditions, including rheumatoid arthritis (RA). In RA the circadian rhythms impact on cellular functions, involving night synthesis and release of proinflammatory cytokines and chemokines, cell migration to inflamed tissues, phagocytosis, proliferative cell response and all are peaking at late night. In chronic inflammatory conditions such as RA, the amplitude of the circadian rhythm of the anti-inflammatory endogenous cortisol availability is not increased as expected and requested, which indicate a reduced night cortisol secretion under the adrenal chronic stress induced by the disease. Therefore, the prevention/treatment of the immune cell night hyperactivity, with related flare of cytokine synthesis and morning RA clinical symptoms, has been shown more effective when the availability of the exogenous glucocorticoids is obtained in the middle of the night (night release). The impressive positive results observed in RA patients treated with modified night release prednisone with a low-dose chronotherapy, seem applicable even for other agents such as conventional NSAIDs and DMARDs, including the positive experimental and clinical results obtained by the night time daily administration of methotrexate. Interestingly, a very recent study showed that methotrexate upregulates important cell circadian genes, resulting in induction of apoptosis in synovial fibroblasts. The link between the circadian rhythms of the disease and the chronotherapy of RA is promising.
- Glycolysis Inhibitors Monoiodoacetate and 2-Deoxyglucose as Antitumor Agents: Experimental Study on Lewis Lung Carcinoma Model. [Journal Article]
- BEBull Exp Biol Med 2018 Sep 17
- Antitumor effects of glycolysis inhibitors monoiodoacetate and 2-deoxyglucose were studied on Lewis lung carcinoma model. Monoiodoacetate exhibited antitumor and antimetastatic activities, being not ...
Antitumor effects of glycolysis inhibitors monoiodoacetate and 2-deoxyglucose were studied on Lewis lung carcinoma model. Monoiodoacetate exhibited antitumor and antimetastatic activities, being not inferior of methotrexate (reference drug); however, the preparation also demonstrated high systemic toxicity. 2-Deoxyglucose exhibited only antitumor effect, while its antimetastatic activity did not differ from the result in the group without treatment.
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- Improved microfluidic platform for simultaneous multiple drug screening towards personalized treatment. [Journal Article]
- BBBiosens Bioelectron 2018 Sep 02
- Development of new targeted therapies is a challenge in the battle against cancer. Although a variety of treatments is currently available, there is no technique for rapidly evaluating the response o...
Development of new targeted therapies is a challenge in the battle against cancer. Although a variety of treatments is currently available, there is no technique for rapidly evaluating the response of cancer patients to the drug. In this work, a microfluidic platform for the real-time simultaneous analysis of the success rate of different nanoparticle based chemotherapeutic drugs is presented. Based on a previous planar chamber and a reported sensitivity enhancing strategy, linear and cross shape microstructures were integrated into the chamber dome of the microfluidic polydimethylsiloxane and glass platform in order to provide a higher fluid mixing and treatment-cell interaction. Several methotrexate (MTX) based treatments (free MTX, MTX loaded Lecithin-PVA nanoparticles, MTX loaded Lecithin-Tween 80 nanoparticles) as well as their respective controls (cell media and both blank nanoparticles) were recirculated through the microchamber over an osteosarcoma cell monolayer. These nanovehicles reduced cell population to less than 20% (LEC-PVA nanoparticles) and 2.3% (LEC-Tween nanoparticles), demonstrating that nanoparticles are a promising target therapy for cancer treatment. Moreover, microstructured platforms demonstrated a higher efficacy in the drug-screening process: due to the liquid folding a higher amount of nanoparticles was internalized by the cells and, therefore, results were observed faster. In fact, the time required to reduce cell viability to the half was nearly a 75% faster. Furthermore, this microfluidic platform offers the capability to test up to five different drugs simultaneously, making it a powerful tool to evaluate the effect of multiple drugs and determine the most effective and personalized treatment.