RESUMO
Pyoderma gangrenosum has been described in association with multiple myeloma and usually affects patients with active/untreated disease. This dermatologic condition was shown to resolve after successful anti-myeloma therapy. We report herein occurrence of pyoderma gangrenosum involving bilateral knees in a patient with multiple myeloma responding to lenalidomide therapy. Previous papers claimed usefulness of thalidomide and its newer derivatives for the therapy of this neutrophilic dermatosis. Occurrence of pyoderma gangrenosum in a myeloma patient responding to lenalidomide would argue against its effectiveness in treating this skin condition. Moreover, the clinical setting suggested that lenalidomide either induced or contributed to the occurrence of pyoderma gangrenosum in our patient. If our hypothesis is correct, we expect more reports of pyoderma gangrenosum with the use of this class of pharmaceuticals.
Assuntos
Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/uso terapêutico , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico , Pioderma Gangrenoso/induzido quimicamente , Talidomida/análogos & derivados , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , Evolução Fatal , Humanos , Joelho/patologia , Lenalidomida , Masculino , Pioderma Gangrenoso/patologia , Pele/patologia , Talidomida/efeitos adversos , Talidomida/uso terapêuticoRESUMO
Interleukin-2 (IL-2) therapy has been demonstrated to induce responses in 10-20% of advanced melanoma and renal cell carcinoma patients, which translates into durable remissions in up to half of the responsers. Unfortunately the use of IL-2 has been associated with severe toxicity and death. It has been previously observed and reported that IL-2 therapy causes a major drop in circulating levels of ascorbic acid (AA). The IL-2 induced toxicity shares many features with sepsis such as capillary leakage, systemic complement activation, and a relatively non-specific rise in inflammatory mediators such as TNF-alpha, C-reactive protein, and in advanced cases organ failure. Animal models and clinical studies have shown rapid depletion of AA in conditions of sepsis and amelioration associated with administration of AA (JTM 9:1-7, 2011). In contrast to other approaches to dealing with IL-2 toxicity, which may also interfere with therapeutic effects, AA possesses the added advantage of having direct antitumor activity through cytotoxic mechanisms and suppression of angiogenesis. Here we present a scientific rationale to support the assessment of intravenous AA as an adjuvant to decrease IL-2 mediated toxicity and possibly increase treatment efficacy.
Assuntos
Ácido Ascórbico/uso terapêutico , Imunoterapia , Interleucina-2/uso terapêutico , Humanos , Infusões Intravenosas , Estresse OxidativoRESUMO
Individuals with malignant melanoma present a variety of immune abnormalities including but not limited to cellular immune dysfunction, antigen presentation deficits, and cytokine production defects. Therefore, enhancing the immune system potential represents an appealing avenue for melanoma therapy. The authors review the immune therapies currently in clinical use as well as the most promising immunotherapy candidates. Ipilimumab, a monoclonal antibody against the CTLA-4, was approved for the therapy of advanced melanoma in 2011. In addition, sizeable anti-melanoma activity has recently been shown with the use of other agents including anti-PD-1/anti-PD-1 ligand antibodies. Consequently, these experimental immunotherapy agents may soon become important items in the anti-melanoma armamentarium.
Assuntos
Anticorpos Monoclonais/farmacologia , Anticorpos Monoclonais/uso terapêutico , Melanoma/terapia , Animais , Anticorpos Monoclonais/imunologia , Antígeno CTLA-4/antagonistas & inibidores , Humanos , Imunoterapia , Ipilimumab , Melanoma/imunologiaRESUMO
Cathelicidin is increased when normal skin is injured and in psoriasis lesions where it has been suggested to play a pivotal role in inflammation through interactions with self-DNA and toll-like receptor 9 (TLR-9) in keratinocytes and plasmacytoid dendritic cells. Because of etanercept's success in treating psoriasis, we hypothesized that etanercept may suppress TLR-9 and cathelicidin induction. Examination of experimentally induced wounds of psoriatic lesional and non-lesional skin, and comparison with wounded normal skin, shows that the induction of cathelicidin and TLR-9 is greatly enhanced in lesional psoriatic skin. Six weeks of etanercept appears not to affect the baseline expression of cathelicidin or TLR-9, but does blunt the induction of cathelicidin in psoriasis with wounding. These findings support the role of cathelicidin in the enhancement of local inflammation in psoriasis and may partially explain one of the mechanisms enabling TNF-α inhibitors to successfully treat this disorder.
Assuntos
Imunidade Inata/efeitos dos fármacos , Imunoglobulina G/farmacologia , Psoríase/tratamento farmacológico , Psoríase/imunologia , Peptídeos Catiônicos Antimicrobianos , Catelicidinas/biossíntese , Etanercepte , Humanos , Imunossupressores/farmacologia , Psoríase/metabolismo , Receptores do Fator de Necrose Tumoral , Receptor Toll-Like 9/biossíntese , Ferimentos e Lesões/tratamento farmacológico , Ferimentos e Lesões/imunologia , Ferimentos e Lesões/metabolismoRESUMO
BACKGROUND: Although the incidence of malignant melanoma in African Americans is considerably lower than in Caucasians, African Americans have a less-favorable prognosis related to later presentation and more deeply invasive lesions at diagnosis. OBJECTIVE: To review the current literature addressing the specific clinical, histopathologic, and molecular features of melanoma in darkly pigmented individuals. METHODS: We reviewed the most up-to-date literature pertaining to melanoma in this patient population, including data from clinical studies, epidemiologic analyses, and molecular and genetic studies. RESULTS: Several studies have suggested differences between lightly and darkly pigmented populations with regard to clinicopathologic character and the underlying genetic processes affecting its pathogenesis. CONCLUSION: Further investigation is warranted to better elucidate the clinical and underlying biological differences in melanoma between Caucasians and African Americans. Such research may help to ameliorate the disparities in melanoma outcomes through improved screening, public health measures aimed at prevention, and potentially novel targeted therapeutic approaches.
Assuntos
Melanoma/etnologia , Melanoma/patologia , Neoplasias Cutâneas/etnologia , Neoplasias Cutâneas/patologia , Pigmentação da Pele , Negro ou Afro-Americano , Disparidades nos Níveis de Saúde , Humanos , Imunoterapia , Melanoma/genética , Melanoma/terapia , Prognóstico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/terapia , Estados Unidos/epidemiologiaRESUMO
Transverse leukonychia (Leukonychia striata or Muehrcke's lines) has been described with the use of several drugs in oncology, mainly chemotherapeutic agents. This condition is thought to represent an abnormality of the vascular nail bed. As the diagnosis is clinical and the condition is self-limited, referral to other specialists is usually not required. We report the first case of transverse leukonychia related to the use of transretinoic acid for acute promyelocytic leukemia. Physician awareness of transverse leukonychia is important in order to reassure the patients and avoid unnecessary (and often not inexpensive) diagnostic work-up.
Assuntos
Antineoplásicos/efeitos adversos , Leucemia Promielocítica Aguda/tratamento farmacológico , Doenças da Unha/induzido quimicamente , Tretinoína/efeitos adversos , Idoso , Antineoplásicos/uso terapêutico , Feminino , Humanos , Doenças da Unha/diagnóstico , Doenças da Unha/patologia , Tretinoína/uso terapêuticoRESUMO
We report the first case of progressive hair repigmentation associated with the use of lenalidomide in an elderly patient with multiple myeloma. The influence of lenalidomide on follicular melanogenesis may involve removing the inhibitory influences of some cytokines such as IL-1, IL-6 and TNF-α. In addition, certain endocrine effects of lenalidomide on the hypophyseal-adrenal axis could explain its action on hair pigmentation. We further hypothesize that lenalidomide may be capable of stimulating migration and/or differentiation of melanocytes to promote repigmentation of gray hair follicles. Pending the clarification of how hair repigmentation occurs with lenalidomide, our observation materializes the concept that hair graying may not be an irreversible process, which opens avenues for targeted therapeutics in the fields of cosmetics and anti-aging medicine.
Assuntos
Inibidores da Angiogênese/farmacologia , Cor de Cabelo/efeitos dos fármacos , Melanócitos/efeitos dos fármacos , Talidomida/análogos & derivados , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Citocinas/metabolismo , Folículo Piloso/efeitos dos fármacos , Folículo Piloso/metabolismo , Humanos , Lenalidomida , Masculino , Melanócitos/metabolismo , Mieloma Múltiplo/tratamento farmacológico , Talidomida/farmacologia , Talidomida/uso terapêuticoRESUMO
Despite the successes of recombinant hematopoietic-stimulatory factors at accelerating bone marrow reconstitution and shortening the neutropenic period post-transplantation, significant challenges remain such as cost, inability to reconstitute thrombocytic lineages, and lack of efficacy in conditions such as aplastic anemia. A possible means of accelerating hematopoietic reconstitution would be administration of cells capable of secreting hematopoietic growth factors. Advantages of this approach would include: a) ability to regulate secretion of cytokines based on biological need; b) long term, localized production of growth factors, alleviating need for systemic administration of factors that possess unintended adverse effects; and c) potential to actively repair the hematopoietic stem cell niche. Here we overview the field of hematopoietic growth factors, discuss previous experiences with mesenchymal stem cells (MSC) in accelerating hematopoiesis, and conclude by putting forth the rationale of utilizing exogenous endothelial cells as a novel cellular therapy for acceleration of hematopoietic recovery.
Assuntos
Células Endoteliais/citologia , Hematopoese , Animais , Células Endoteliais/metabolismo , Fatores de Crescimento de Células Hematopoéticas/metabolismo , Transplante de Células-Tronco Hematopoéticas , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Nicho de Células-TroncoRESUMO
BORIS, or CTCFL, the so called Brother of the Regulator of Imprinted Sites because of the extensive homology in the central DNA binding region of the protein to the related regulator, CTCF, is expressed in early gametogenesis and in multiple cancers but not in differentiated somatic cells. Thus it is a member of the cancer testes antigen group (CTAs). Since BORIS and CTCF target common DNA binding sites, these proteins function on two levels, the first level is their regulation via the methylation context of the DNA target site and the second level is their distinct and different epigenetic associations due to differences in the non-homologous termini of the proteins. The regulation on both of these levels is extensive and complex and the sphere of influence of each of these proteins is associated with vastly different cellular signaling processes. On the level of gene expression, BORIS has three known promoters and multiple spliced mRNAs which adds another level of complexity to this intriguing regulator. BORIS expression is observed in the majority of cancer tissues and cell lines analyzed up to today. The expression profile and essential role of BORIS in cancer make this molecule very attractive target for cancer immunotherapy. This review summarizes what is known about BORIS regarding its expression, structure, and function and then presents some theoretical considerations with respect to its genome wide influence and its potential for use as a vaccine for cancer immunotherapy.
Assuntos
Proteínas de Ligação a DNA/metabolismo , Epigênese Genética , Genoma Humano/genética , Fator de Ligação a CCCTC , Proteínas de Ligação a DNA/genética , Humanos , Neoplasias/genética , Neoplasias/imunologia , Neoplasias/terapia , Ligação Proteica , Proteínas RepressorasRESUMO
The history of ascorbic acid (AA) and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS) and multi organ failure (MOF), has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop septic symptoms, a further decrease in ascorbic acid levels occurs. Given the known role of ascorbate in: a) maintaining endothelial and suppression of inflammatory markers; b) protection from sepsis in animal models; and c) direct antineoplastic effects, we propose the use of ascorbate as an adjuvant to existing modalities in the treatment and prevention of cancer-associated sepsis.
Assuntos
Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/uso terapêutico , Neoplasias/complicações , Sepse/tratamento farmacológico , Sepse/prevenção & controle , Ácido Ascórbico/farmacologia , Deficiência de Ácido Ascórbico/complicações , Endotélio/efeitos dos fármacos , Endotélio/fisiopatologia , Humanos , Imunidade/efeitos dos fármacos , Injeções Intravenosas , Sepse/etiologia , Sepse/fisiopatologiaRESUMO
OBJECTIVES: Subjects with polycystic ovary syndrome (PCOS) were shown to carry an increased long-term cardiovascular risk. Systemic inflammation and reactive leukocytosis have also been described in PCOS. Recent research suggests the presence of an increased thrombotic risk in these patients. METHODS: We describe a cohort of PCOS patients presenting with persistent thrombocytosis. Our cohort included women aged 20-37 who also had moderate leukocytosis and neutrophilia. They showed normal mean platelet volume and platelet aggregation. We excluded any myeloproliferative conditions in all patients. RESULTS: The mean platelet count and standard deviation (SD) at presentation were 587 ± 61 × 10/L (normal 140-440 × 10/L). Median C-reactive protein (CRP) was 1.66 (range 1.2-2.2, normal <1 mg/dL). The platelet counts did not correlate with the CRP levels in our patients (Pearson correlation coefficient 0.171 and 0.170, respectively, P = 0.08). CONCLUSION: While the inflammatory state of PCOS could play a role in triggering an increased platelet count, the persistent thrombocytosis in our patients did not correlate with the CRP levels. Therefore, from an etiological perspective, thrombocytosis appears to be at least partially independent from the classical pathways of systemic inflammation. The preexisting procoagulant state in PCOS due to coagulation cascade stimulation, platelet activation, and endothelial dysfunction may be further fueled by the presence of persistent thrombocytosis. We propose a unique model for cardiovascular risk assessment in women with PCOS to include not only the classic cardiovascular risk factors, but also the parameters related to the proinflammatory and procoagulant tendencies manifested in PCOS.
Assuntos
Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/complicações , Trombocitose/sangue , Trombocitose/etiologia , Adulto , Proteína C-Reativa/metabolismo , Estudos de Coortes , Feminino , Humanos , Leucocitose/sangue , Leucocitose/complicações , Leucocitose/fisiopatologia , Neutropenia/sangue , Neutropenia/complicações , Neutropenia/fisiopatologia , Agregação Plaquetária , Contagem de Plaquetas , Síndrome do Ovário Policístico/fisiopatologia , Trombocitose/terapia , Adulto JovemRESUMO
BACKGROUND: Whereas the association between multisystem and pulmonary sarcoidosis and malignancy has been documented, a relationship between cutaneous sarcoidosis and neoplasia has not yet been reported. Because cutaneous manifestations are seen in 20-25 percent of cases of sarcoidosis, this association deserves further investigation. METHODS: We reviewed the relevant literature, in addition to our case series, for a total of 110 cases of cutaneous and non-cutaneous sarcoidosis associated with malignancy with the aim of analyzing possible associations between cutaneous sarcoidosis and malignancy and to enhance the dermatologist's understanding of their critical role in the management of this disease. A search for consecutive cases, which were encountered during the past 20 years, identified 10 cases of confirmed cutaneous sarcoidosis. A review of the relevant literature was also conducted to identify cases of malignancy associated with cutaneous and non-cutaneous sarcoidosis. RESULTS: Cutaneous localization of sarcoidosis was identified in 58 of 100 patients with sarcoidosis and cancer found in the literature (58%) and in 4 of 10 patients in our series (40%). In our series, all cases manifested solid tumors, including breast (n=4 tumors), prostate cancer, colon cancer, kidney cancer, and squamous cell carcinoma of the skin (n=1 of each type). Among the 6 patients in our series with cancers and non-cutaneous sarcoidosis, the types of neoplasias encountered were renal cancer (n=1), mycosis fungoides (n=1), diffuse large B-cell lymphoma (n=1), colon cancer (n=1), and ADK of parotid (n=2). Neoplasias developed after an average of 7.14 years in the literature cases and eight years in our series, following the diagnosis of sarcoidosis. Among the 100 cases of cutaneous (n=58) and non-cutaneous (n=42) sarcoidosis associates with malignancy, which were extracted from the literature, hematologic malignancies accounted for 73 percent of cases and sarcoidosis preceded the detection of neoplasia in a majority (76%) of cases. Among 110 total cases analyzed in this paper, cutaneous sarcoidosis was confirmed in 56.4 percent of overall cases, a figure exceeding expected rates of cutaneous involvement (20-25%) in the general sarcoidosis population. CONCLUSIONS: Sarcoidosis with cutaneous manifestations appears to be associated with malignancy, possibly at a higher rate than other systemic forms of sarcoidosis. The predominant occurrence of sarcoidosis before the development of neoplasia may indicate that an immune dysregulation, such as impairment of cellular immunity mediated by sarcoidosis or the effects of treatment may contribute to an increased risk of malignancy in predisposed individuals. Physician recognition of this link between sarcoidosis and malignancy is critical. Dermatologists, in particular, play an important role, given that many of these associated cases manifest initially, or even solely, with cutaneous findings.
Assuntos
Neoplasias/complicações , Sarcoidose/complicações , Dermatopatias/complicações , Humanos , Pessoa de Meia-Idade , Sarcoidose/patologia , Dermatopatias/patologiaRESUMO
A various array of cutaneous granulomatous disorders have been found to be associated with internal malignancy. Among them, sarcoidosis, granuloma anulare (GA), psoriasis, pyoderma gangrenosum (PG), or other neutrophilic dermatoses such as the Sweet syndrome and subcorneal pustular dermatosis may precede the development of a neoplastic process by months or years. Pathogenic links of inflammation with cancer are discussed, including inflammation, intrinsic immune dysfunction, cytokines and interleukins, angiogenetic factors, and epigenetic changes.
Assuntos
Granuloma/complicações , Neoplasias/fisiopatologia , Síndromes Paraneoplásicas , Dermatopatias/complicações , Granuloma/fisiopatologia , Humanos , Inflamação , Neoplasias/complicações , Sarcoidose/complicações , Sarcoidose/fisiopatologiaRESUMO
BACKGROUND: Magnetic resonance imaging has been used in the diagnosis of human prion diseases such as sCJD and vCJD, but patients are scanned only when clinical signs appear, often at the late stage of disease. This study attempts to answer the questions "Could MRI detect prion diseases before clinical symptoms appear?, and if so, with what confidence?" METHODS: Scrapie, the prion disease of sheep, was chosen for the study because sheep can fit into a human sized MRI scanner (and there were no large animal MRI scanners at the time of this study), and because the USDA had, at the time of the study, a sizeable sample of scrapie exposed sheep, which we were able to use for this purpose. 111 genetically susceptible sheep that were naturally exposed to scrapie were used in this study. RESULTS: Our MRI findings revealed no clear, consistent hyperintense or hypointense signal changes in the brain on either clinically affected or asymptomatic positive animals on any sequence. However, in all 37 PrPSc positive sheep (28 asymptomatic and 9 symptomatic), there was a greater ventricle to cerebrum area ratio on MRI compared to 74 PrPSc negative sheep from the scrapie exposed flock and 6 control sheep from certified scrapie free flocks as defined by immunohistochemistry (IHC). CONCLUSIONS: Our findings indicate that MRI imaging can detect diffuse cerebral atrophy in asymptomatic and symptomatic sheep infected with scrapie. Nine of these 37 positive sheep, including 2 one-year old animals, were PrPSc positive only in lymph tissues but PrPSc negative in the brain. This suggests either 1) that the cerebral atrophy/neuronal loss is not directly related to the accumulation of PrPSc within the brain or 2) that the amount of PrPSc in the brain is below the detectable limits of the utilized immunohistochemistry assay. The significance of these findings remains to be confirmed in human subjects with CJD.
Assuntos
Encéfalo/patologia , Síndrome de Creutzfeldt-Jakob/patologia , Modelos Animais de Doenças , Imageamento por Ressonância Magnética , Animais , Atrofia , Ventrículos Cerebrais/patologia , Humanos , Tamanho do Órgão , Curva ROC , OvinosRESUMO
The medical use of low level laser (LLL) irradiation has been occurring for decades, primarily in the area of tissue healing and inflammatory conditions. Despite little mechanistic knowledge, the concept of a non-invasive, non-thermal intervention that has the potential to modulate regenerative processes is worthy of attention when searching for novel methods of augmenting stem cell-based therapies. Here we discuss the use of LLL irradiation as a "photoceutical" for enhancing production of stem cell growth/chemoattractant factors, stimulation of angiogenesis, and directly augmenting proliferation of stem cells. The combination of LLL together with allogeneic and autologous stem cells, as well as post-mobilization directing of stem cells will be discussed.
Assuntos
Terapia com Luz de Baixa Intensidade , Doença Pulmonar Obstrutiva Crônica/terapia , Células-Tronco , Animais , Diferenciação Celular/efeitos da radiação , Proliferação de Células/efeitos da radiação , Ensaios Clínicos como Assunto , Humanos , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Neovascularização Fisiológica/efeitos da radiação , Transplante de Células-Tronco , Células-Tronco/fisiologia , Células-Tronco/efeitos da radiaçãoRESUMO
Induction of tumor-specific immunity is an attractive approach to cancer therapy, however to date every major pivotal trial has resulted in failure. While the phenomena of tumor-mediated immune suppression has been known for decades, only recently have specific molecular pathways been elucidated, and for the first time, rationale means of intervening and observing results of intervention have been developed. In this review we describe major advances in our understanding of tumor escape from immunological pressure and provide some possible therapeutic scenarios for enhancement of efficacy in future cancer vaccine trials.
Assuntos
Antígenos de Neoplasias , Vacinas Anticâncer/imunologia , Vacinas Anticâncer/uso terapêutico , Neoplasias/imunologia , Neoplasias/terapia , Células Dendríticas/imunologia , Humanos , Tolerância Imunológica/imunologia , Estresse Oxidativo , Linfócitos T/imunologiaRESUMO
Since the days of Medawar, the goal of therapeutic tolerogenesis has been a "Holy Grail" for immunologists. While knowledge of cellular and molecular mechanisms of this process has been increasing at an exponential rate, clinical progress has been minimal. To provide a mechanistic background of tolerogenesis, we overview common processes in the naturally occurring examples of: pregnancy, cancer, oral tolerance and anterior chamber associated immune deviation. The case is made that an easily accessible byproduct of plastic surgery, the adipose stromal vascular fraction, contains elements directly capable of promoting tolerogenesis such as T regulatory cells and inhibitory macrophages. The high content of mesenchymal and hematopoietic stem cells from this source provides the possibility of trophic/regenerative potential, which would augment tolerogenic processes by decreasing ongoing inflammation. We discuss the application of this autologous cell source in the context of rheumatoid arthritis, concluding with some practical examples of its applications.
Assuntos
Tecido Adiposo/patologia , Artrite Reumatoide/imunologia , Transplante de Células-Tronco Hematopoéticas , Articulações/patologia , Células Estromais/patologia , Tecido Adiposo/cirurgia , Tecido Adiposo/transplante , Idoso , Animais , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/patologia , Artrite Reumatoide/fisiopatologia , Artrite Reumatoide/terapia , Autoanticorpos/biossíntese , Autoanticorpos/sangue , Autoanticorpos/genética , Células Cultivadas , Feminino , Humanos , Articulações/metabolismo , Lipectomia , Células-Tronco Mesenquimais/imunologia , Atividade Motora , Peptídeos Cíclicos/imunologia , Fator Reumatoide/biossíntese , Fator Reumatoide/sangue , Fator Reumatoide/genética , Nicho de Células-Tronco , Células Estromais/transplante , Linfócitos T Reguladores/imunologiaRESUMO
Duchenne muscular dystrophy (DMD) is a lethal X-linked musculodegenerative condition consisting of an underlying genetic defect whose manifestation is augmented by inflammatory mechanisms. Previous treatment approaches using gene replacement, exon-skipping or allogeneic cell therapy have been relatively unsuccessful. The only intervention to mediate improvement in survival, albeit minor, is glucocorticoid treatment. Given this modality appears to function via suppression of underlying inflammation; we focus this review on the inflammatory response as a target for mesenchymal stem cell (MSC) therapy. In contrast to other cell based therapies attempted in DMD, MSC have the advantages of (a) ability to fuse with and genetically complement dystrophic muscle; (b) possess anti-inflammatory activities; and (c) produce trophic factors that may augment activity of endogenous repair cells. We conclude by describing one practical scenario of stem cell therapy for DMD.
Assuntos
Inflamação/imunologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/imunologia , Distrofia Muscular de Duchenne/cirurgia , Animais , Diferenciação Celular , Humanos , Células-Tronco Mesenquimais/citologia , Músculo Esquelético/imunologia , Músculo Esquelético/patologia , Distrofia Muscular de Duchenne/imunologia , Resultado do TratamentoRESUMO
PURPOSE: Retrospective analysis of two recent multiple myeloma (MM) clinical trials suggested that the use of bortezomib may be associated with an increased incidence of herpes zoster infections. Therefore, prophylactic use of antivirals has been advocated by some authors. This article explores the potential risks and pitfalls linked to routine acyclovir prophylaxis in bortezomib-treated MM. SUMMARY: use of antivirals can be associated with important nephro- and neurotoxicity. The nephrotoxicity induced by MM itself and its supportive therapies, superimposed to aging and inherent immunosuppression in myeloma, makes the development of renal impairment even more likely. On the other hand, sensory neuropathy is known to occur both during myeloma progression and in the setting of bortezomib therapy. Furthermore, preexisting nephropathy in MM patients can contribute to the occurrence of serious neurologic toxicity with acyclovir. CONCLUSIONS: long-term acyclovir prophylaxis in MM patients treated with bortezomib may cause severe renal and neurological toxicity. Prevention of these complications can be achieved through either withholding of the antivirals or a very close monitoring of both neurologic status and renal function in this patient population. This highlights the importance of both clinician's and pharmacist's involvement in optimization of myeloma patient care.