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.
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.
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.
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 etanercepts 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-? inhibitors to successfully treat this disorder.
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.
Transverse leukonychia (Leukonychia striata or Muehrckes 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.
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.
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.
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.
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.
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.
Kulchitsky cells represent the cells of origin of small cell lung cancer (SCLC). They display an antigenic makeup characteristic of both the neural crest and epithelium and have been shown to secrete both polypeptide hormones and enzymes. The coexistence of two or more (concomitant or sequential) paraneoplastic endocrine syndromes is possible with SCLC, and paraneoplastic amylase production has also been described with this malignancy. We present here the first patient with an extensive stage SCLC, exhibiting a marked paraneoplastic lipase production and a syndrome of inappropriate antidiuretic hormone (SIADH) secretion. In our patient, the paraneoplastic hyperlipasemia paralleled both the initial SCLC response to chemotherapy and its subsequent clinicoradiological relapse.
Immunotherapy is an important modality in the therapy of patients with malignant melanoma. As our knowledge about this disease continues to expand, so does the immunotherapeutic armamentarium. Nevertheless, successful preclinical models do not always translate into clinically meaningful results. The authors give a comprehensive analysis of most recent advances in the immune anti-melanoma therapy, including interleukins, interferons, other cytokines, adoptive immunotherapy, biochemotherapy, as well as the use of different vaccines. We also present the fundamental concepts behind various immune enhancement strategies, passive immunotherapy, as well as the use of immune adjuvants. This review brings into discussion the results of newer and older clinical trials, as well as potential limitations and drawbacks seen with the utilization of various immune therapies in malignant melanoma. Development of novel therapeutic approaches, along with optimization of existing therapies, continues to hold a great promise in the field of melanoma therapy research. Use of anti-CTLA4 and anti-PD1 antibodies, realization of the importance of co-stimulatory signals, which translated into the use of agonist CD40 monoclonal antibodies, as well as activation of innate immunity through enhanced expression of co-stimulatory molecules on the surface of dendritic cells by TLR agonists are only a few items on the list of recent advances in the treatment of melanoma. The need to engineer better immune interactions and to boost positive feedback loops appear crucial for the future of melanoma therapy, which ultimately resides in our understanding of the complexity of immune responses in this disease.
Non-Hodgkin lymphoma (NHL) occurs in the setting of methotrexate (MTX) therapy for rheumatoid arthritis. However, it has been very rarely reported in subjects with psoriatic arthritis treated with MTX. We report here a case of a 70-year-old woman with psoriatic arthritis who presented with bilateral lung infiltrates, pleural effusion, splenomegaly, and inguinal lymphadenopathy during treatment with MTX. The diagnosis of diffuse large B-cell lymphoma was made by analysis of the pleural fluid via thoracentesis and biopsy of an enlarged inguinal lymph node. Clinicians should consider the possibility of a NHL complicating psoriasis and with MTX therapy in order to prevent treatment delays.
Although infiltration of the gallbladder by lymphoma is rare, it has to be considered in the differential diagnosis of patients presenting with cholecystitis-like symptoms. The most common lymphomas masquerading as acute cholecystitis are mucosa-associated lymphoid tissue lymphoma and large B-cell lymphoma. We describe a 75-year-old patient who presented with an acute cholecystitis-like picture, featuring chronic lymphocytic leukemia (CLL) with gallbladder wall involvement as the initial disease presentation. The cholecystectomy specimen showed perineural invasion present within the gallbladder wall, which likely accounted for the patients right upper quadrant abdominal tenderness. In this way, we would like to alert clinicians and pathologists alike to CLL as yet another cause of a cholecystitis-like symptomatology.
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?"
Diagnosis of cutaneous melanoma requires accurate differentiation of true malignant tumors from highly atypical lesions, which lack the capacity to develop uncontrolled proliferation and to metastasize. We used melanoma markers from previous work to differentiate benign and atypical lesions from melanoma using paraffin-embedded tissue. This critical step in diagnosis generates the most uncertainty and discrepancy between dermatopathologists. A total of 193 biopsy tissues were selected: 47 melanomas, 48 benign nevi, and 98 atypical/suspicious, including 48 atypical nevi and 50 melanomas as later assigned by expert dermatopathologists. Performance for SILV, GDF15, and L1CAM normalized to TYR in unequivocal melanoma versus benign nevi resulted in an area under the curve (AUC) of 0.94, 0.67, and 0.5, respectively. SILV also differentiated atypical cases classified as melanoma from atypical nevi with an AUC=0.74. Furthermore, SILV showed a significant difference between suspicious melanoma and each suspicious atypia group: melanoma versus severe atypia and melanoma versus moderate atypia had P-values of 0.0077 and 0.0009, respectively. SILV showed clear discrimination between melanoma and benign unequivocal cases as well as between different atypia subgroups in the group of suspicious samples. The role and potential utility of this molecular assay as an adjunct to the morphological diagnosis of melanoma are discussed.
Melanoma is the deadliest form of all skin cancers and is highly linked to sun-related behavior in patients. However, sun-protection behavior to prevent melanoma in this population has been shown to be inadequate to date. The objective of this study was to compare changes in sun protection habit before and after patients diagnosis with malignant melanoma. The study also seeks patients advice on how to improve public education on melanoma prevention. A retrospective survey study was conducted on 68 respondents of patients diagnosed with melanoma from six different dermatologic practices in various boroughs of New York and Long Island in the state of New York by telephone interviews. There was a significant positive change in patients sun-protection behavior after they were diagnosed with melanoma. Various methods of sun protection, such as avoiding sun exposure, applying and reapplying sunscreen, and wearing protective clothing were practiced more frequently after diagnosis. In addition, the frequency of sunbathing decreased drastically. Most patients were aware about the dangers of sun exposure before their diagnosis. They, however, did not feel the need to adopt sun-protection measures before their diagnosis. Respondents advised that education on dangers to excess sun exposure should be provided at an early age through multiple venues. The study reflected that 71% of diagnosed patients who completed the survey were informed about sun protection before their diagnosis. Many patients did not follow strict guidelines to prevent sun damage as shown by their behaviors before diagnosis. Diagnosis of the disease was apparently the main motivating factor to initiate challenging behavioral changes.
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.
Patients with congestive heart failure (CHF) that are not eligible for transplantation have limited therapeutic options. Stem cell therapy such as autologous bone marrow, mobilized peripheral blood, or purified cells thereof has been used clinically since 2001. To date over 1000 patients have received cellular therapy as part of randomized trials, with the general consensus being that a moderate but statistically significant benefit occurs. Therefore, one of the important next steps in the field is optimization. In this paper we discuss three ways to approach this issue: a) increasing stem cell migration to the heart; b) augmenting stem cell activity; and c) combining existing stem cell therapies to recapitulate a "therapeutic niche". We conclude by describing a case report of a heart failure patient treated with a combination stem cell protocol in an attempt to augment beneficial aspects of cord blood CD34 cells and mesenchymal-like stem cells.
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.
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.
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.
The rapidly increasing incidence of melanoma occurs at the same time as an increase in general healthcare costs, particularly the expenses associated with cancer care. Previous cost estimates in melanoma have not utilized a dynamic model considering the evolution of the disease and have not integrated the multiple costs associated with different aspects of medical interventions and patient-related factors. Futhermore, previous calculations have not been updated to reflect the modern tendencies in healthcare costs.
Endothelial dysfunction is associated with major causes of morbidity and mortality, as well as numerous age-related conditions. The possibility of preserving or even rejuvenating endothelial function offers a potent means of preventing/treating some of the most fearful aspects of aging such as loss of mental, cardiovascular, and sexual function.Endothelial precursor cells (EPC) provide a continual source of replenishment for damaged or senescent blood vessels. In this review we discuss the biological relevance of circulating EPC in a variety of pathologies in order to build the case that these cells act as an endogenous mechanism of regeneration. Factors controlling EPC mobilization, migration, and function, as well as therapeutic interventions based on mobilization of EPC will be reviewed. We conclude by discussing several clinically-relevant approaches to EPC mobilization and provide preliminary data on a food supplement, Stem-Kine, which enhanced EPC mobilization in human subjects.
Family environment probably represents a high route of transmission for H. pylori, a bacterium associated with gastric cancer (GC). We report two cases of GC in a husband-wife pair of immigrants from Romania. The disease was first diagnosed in the wife, and three years later in her husband of 55 years. Both patients had active H. pylori-related inflammation. Household family members of GC patients could be infected with a shared H. pylori strain, putting them at risk for developing the disease. Therefore, it may be justified to identify and eradicate the H. pylori infection in such family members early, before the neoplastic changes become irreversible.
Although most cases of prekallikrein deficiency are asymptomatic, a few reports link severe prekallikrein deficiency with thrombotic phenomena and recurrent pregnancy loss. Here, we present a case of a Jamaican female patient with prekallikrein deficiency, associated with a severe bleeding diathesis. A low level of plasma prekallikrein activity, along with the presence of C529Y mutation, confirmed the diagnosis in our patient. Some animals with prekallikrein deficiency were shown to have moderate bleeding tendencies. Furthermore, the first patient with prekallikrein deficiency from the African continent was a young child who presented with severe, hemophilia-like bleeding, featuring recurrent hemarthrosis and subcutaneous hematomas. We find it intriguing that our patient is of African heritage and presented with a moderate nasal bleeding tendency in her youth, followed by severe recurrent mucosal bleeding later in life.
Bisphosphonates are associated with an important number of inflammatory ocular side-effects including but not limited to conjunctivitis, episcleritis, scleritis, uveitis, and optic neuritis. The intravenous bisphosphonates appear to be linked with more severe ocular inflammation than the orally administered ones. These eye complications tend to resolve with the bisphosphonate discontinuation and can re-occur with its re-challenge. We present here the first case of an acute retinal pigment epithelial detachment associated with pamidronate infusion in a 59-year-old patient with metastatic prostate cancer.
Sea urchin injuries have been associated with a variety of cutaneous lesions, ranging from acute, transient reactions, to more chronic inflammatory conditions that result in the formation of granulomas. Although diverse species of sea urchins have been reported to produce chronic cutaneous granulomas, the two most prevalent organisms found on the US West Coast, purple and red sea urchins (Strongylocentrotus purpuratus and Strongylocentrotus franciscanus), have not yet been reported to induce persistent granulomatosis in humans. We describe one case of a 35-year-old marine biologist with chronic cutaneous lesions produced after repeated exposures. The lesions were similar to the ones produced by other urchin species, consisting of small, firm, erythematous nodules on his palms, dorsum of the hands, elbows, and knees. Increased awareness of this condition, including its association with the two prevalent organisms on the West Coast, should lead to a more rapid diagnosis for those affected. This article reviews the types of injuries, clinical cutaneoous lesions, histopathological features, and pathogenesis of the chronic inflammatory process induced by sea urchins.
Carboplatin-gemcitabine doublet is an important therapeutic option for patients with both previously treated and untreated ovarian cancer (OC). At the currently recommended dosing, its main toxicity is hematological, consisting of thrombocytopenia, neutropenia, including febrile neutropenia, and/or anemia. The use of platelet transfusions, G-CSF and/ or packed red blood cells is often necessary, in order to avoid treatment delays or omission of doses. We report here on the high efficacy of lower doses of gemcitabine at 750 mg/m(2) on days 1 and 8 in combination with carboplatin AUC = 4 on day 1, repeated in 21-day cycles, in a small series of patients with advanced/metastatic OC. Using the above dose regimen, durable complete remissions were achieved in all patients in our cohort within 9-12 weeks, with no growth factor support, and no transfusions of blood components being necessary. We believe that lowering the doses of both carboplatin and gemcitabine from the start of therapy would ensure their timely delivery and steady-state plasma drug levels. In conclusion, administration of carboplatin AUC = 4 and gemcitabine 750 mg/m(2) appears to be a safe and effective combination for the therapy of advanced/metastatic OC, with clinically tolerable hematological toxicity.
Medications belonging to the group of epidermal growth factor (EGFR) inhibitors are currently in widespread use for the treatment of epithelial malignancies. Many cutaneous side effects are known to develop as a result of the use of these agents. Trichomegaly is a newly described side effect, consisting of premature maturation (terminal differentiation) of the hair of the eyelashes and the scalp, which is characterized by a hairy phenotype. Although occurrence of the acneiform skin rash is clearly associated with favorable tumor responses and improvement in patient survival during the use of EGFR inhibitors for the treatment of cancer, the significance of trichomegaly is less clear. A review of all published cases is provided, leading to the observation that trichomegaly also developed in patients whose tumors had a positive response to anti-EGFR therapy. The apparent lack of the development of tolerance to this medication effect and, therefore, the continued clinical sign of trichomegaly is in contrast to the time-limited nature of other cutaneous side effects of EGFR inhibitors, such as the classical papulo-pustular rash. The persistence of trichomegaly in some patients brings into question the precise mechanism of this phenomenon and suggests the possibility of using EGFR inhibition therapeutically to stimulate hair growth.
The influences exerted by the epidermal growth factor receptor (EGFR) on the skin act at multiple levels, which involve compartments that normally express EGFR. These include the basal and suprabasal layers of the epidermis, sebaceous glands, and the outer root sheath of the hair follicles. The physiological roles of EGFR ensure epidermal renewal and integrity, along with a gatekeeping and function and hair growth stimulation functions. Important cellular functions that are altered during EGF receptor blocking therapy consist of epidermal differentiation, proliferation, apoptosis, and migration, with an overall dominating effect of inducing growth arrest and terminal differentiation of the keratinocytes in the basal layers. The effects of EGFR blockage on the hair cycle include terminal differentiation of the hair follicle, which in certain cases may be associated with trichomegaly. Trichomegaly of the eyelashes may occur as an isolated occurrence or, frequently, as part of a generalized phenomenon that may be associated with the use of the EGFR inhibitors. Molecular changes associated with EGFR blockage are discussed, relevant to their association with hair growth. Modulation of Akt, AP2alpha, CDK4, Notch-1, p27KIP1, and Hedgehog expression are involved in the initiation of the hair cycle and inducement of the anagen phase, followed by proliferation and differentiation of the hair follicles. Epidermal growth factor receptor inhibitors have been developed as therapeutic molecules directed against cancer; in these regimens the knowledge of EGF receptor signaling functions has been translated into significant clinical results. However, among their various collateral effects on the skin, hair growth is observed to occur in certain patients. A particular "wavy" hair phenotype is observed during the pharmacological EGFR receptor blockade, just as in murine transgenic models that carry loss of function of TGF-alpha or EGFR genes. A better characterization of the individual roles pertaining to the EGF family ligands and receptors, has the potential provide new strategies for the management of hair loss.
Although relatively uncommon, malignant melanoma in African-Americans and other minority ethnic populations represents an aggressive disease highly associated with invasive lesions and a more advanced stage of disease at diagnosis, and consequently with a decreased survival compared with Caucasians. Data on biology of melanoma in African-Americans is very limited, which complicates the analysis of epidemiological information, as well as identification of accurate prognostic variables. This review article explores critical features of melanoma in African-Americans that distinguish it from disease seen in Caucasians, including the clinical presentation, histological patterns, prognostic indicators, and etiology. Emerging data from biologic and genetic studies will also be discussed, raising the possibility that melanoma in pigmented skin may represent molecular distinct cancers that are inherently more aggressive. Improved understanding of the unique manifestations of melanoma in African-Americans, and its underlying tumor biology, will help improve clinical detection, optimize preventative measures through public health education, and potentially lead to the development of novel targeted therapeutic approaches.
Lenalidomide is an important contemporary treatment option for patients with multiple myeloma (MM). Rare instances of autoimmune conditions have been observed in association with its use. Although moderate myelosuppression is not uncommonly seen in patients treated with lenalidomide, aplastic anemia has not previously been reported to be associated with this agent. We describe a case of severe aplastic anemia (AA) that was probably induced by lenalidomide. A 64-year-old male patient developed progressive pancytopenia three weeks into therapy with lenalidomide for his relapsed MM. A bone marrow aspirate and biopsy confirmed the diagnosis of AA and suggested the existence of an immunological reaction at the level of marrow. A gradual spontaneous recovery of normal hematopoiesis followed after the lenalidomide discontinuation.
The mammalian target of rapamycin (mTOR) pathway inhibition has emerged as one of the main directions for the development of new targeted agents in renal cell carcinoma (RCC). A prominent member in its class of medications, temsirolimus has already been shown to improve overall survival in advanced kidney cancer, when compared with the previous standard, IFN-alpha.
We present a case featuring a unique overlap between the body areas involved by lung adenocarcinoma and the cutaneous paraneoplastic sign of Leser-Trélat. In our patient, the Leser-Trélat sign consisted of explosive multiple seborrheic keratoses in combination with acanthosis nigricans, representing a remarkable geometric skin projection of lung cancer which involved both the upper lobes. Our case suggests a unique interrelation between the paraneoplastic sign of Leser-Trélat and the tumor itself. The recognition of this phenomenon may contribute to an early diagnosis and prompt surgical treatment of occult cancers.
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.
The simultaneous advances in engineering, medicine, and molecular biology have accelerated the pace of introductions of new light-based technologies in dermatology. In this review, the authors examine recent advances in laser surgery as well as peer into the future of energy-based cutaneous medicine. The future landscape of dermatology will almost undoubtedly include (1) noninvasive imaging technologies and (2) improved "destructive" modalities based on real-time feedback from the skin surface.
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-?. 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.
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