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Chronic erythematous rash and lesions on trunk and limbs
Published in Richard Ashton, Barbara Leppard, Differential Diagnosis in Dermatology, 2021
Richard Ashton, Barbara Leppard
A T-cell lymphoma is usually confined to the skin. It presents as itchy red scaly patches (Fig. 8.75 & 8. 76) that may mimic either eczema or psoriasis. The main differentiating feature is that individual lesions are of different colours, so that some patches are pink, others red or orange brown.
Involvement of Dopamine with Various Cancers
Published in Nira Ben-Jonathan, Dopamine, 2020
T-cell lymphomas account for ~15% of all NHLs. There are many forms of T-cell lymphomas, which can be aggressive or indolent [14]. Jurkat cells are an immortalized human T-lymphocyte cell line that was originally obtained from the peripheral blood of a boy with T cell leukemia. They are commonly used to study T-cell signaling, apoptosis, and expression of chemokine receptors susceptible to vial entry, particularly HIV. Jurkat lymphocytes express many components of the DA system: DAT and vesicular monoamine transporter (VMAT), D1-like and D2-like receptors, confirming their ability to internalize, store and respond to DA. Yet, they lack TH expression and do not synthesize DA de novo [15]. To examine the effects of DA on HIV-1 gene transcription, a reporter containing the full length long terminal repeat of HIV-1 was transfected into Jurkat cells [16]. Large doses of DA (50–200 μM) stimulated HIV-1 transcription via nuclear factor kappa B (NF-κB) activation. The combination of DA and tumor necrosis factor alpha (TNF-α) increased HIV-1 transcription as well as replication. Others reported that D1R activation inhibited cell proliferation in T-cells from normal volunteers but failed to do so in Jurkat cells because of overexpression of phosphodiesterase (PDE) activity [17].
The lymphoreticular system and bone marrow
Published in C. Simon Herrington, Muir's Textbook of Pathology, 2020
In the past, T-cell lymphomas have been difficult to classify, and many are now included under the general category of peripheral T-cell lymphoma, not otherwise specified (NOS). Most of these are nodal tumours showing, as a rule, a pleomorphic cellular picture due to varying admixtures of small lymphoid elements and transformed cells (immunoblasts) with a correspondingly unpredictable, but usually poor, prognosis.
Approved and emerging PI3K inhibitors for the treatment of chronic lymphocytic leukemia and non-Hodgkin lymphoma
Published in Expert Opinion on Pharmacotherapy, 2020
Dirk L. Kienle, Stephan Stilgenbauer
T-cell lymphomas represent an area of particular unmet need due to their rarity with limited-approved treatment options and their poor prognosis with high recurrence rates after conventional chemotherapy. As part of the larger phase 1 trial including patients with CLL and B-NHL [31], see ‘Pi3Ki in CLL→ Duvelisib’), a subgroup of patients with peripheral T-cell lymphomas (PTCL, n = 16) and cutaneous T-cell lymphomas (CTCL, n = 19) was included [58]. The safety profile was comparable to the patients with B-NHL. ORR was 50.0% and 31.6% in PTCL and CTCL patients, respectively, including 3 complete responses. Concomittent in-vitro studies gave further insight into the mechanisms of action of duvelisib in T-NHL. Among 11 T-NHL cell lines under study, all cell lines showed expression of PI3Kgamma and 4 showed constitutive AKT activation. Duvelisib induced killing in three of these four cell lines, while no killing was observed in cell lines lacking AKT activation indicating that AKT activation is a prerequisite for duvelisib efficacy. Moreover, duvelisib induced a shift of the microenvironment in PTCL patient-derived xenograft from an immunosuppressive to an inflammatory phenotype [58]. A phase 2 trial investigating duvelisib monotherapy in R/R PTCL is ongoig (NCT03372057). In addition, the combination of duvelisib with either Romidepsin or Bortezomib is explored in patients with R/R T-cell Lymphomas in phase 1 (NCT02783625).
Cancer risk in patients with psoriasis: should we be paying more attention?
Published in Expert Review of Clinical Immunology, 2020
Nikolai Dyrberg Loft, Sofie Vaengebjerg, Lone Skov
One possible contributing factor for the observed associations might be surveillance bias. Patients with psoriasis visit a dermatologist frequently and as dermatologists are experts in identifying NMSC, this might in part explain the overrepresentation. Few studies have a reference group with a skin disease, which could overcome this issue. Again, for cutaneous T-cell lymphoma (CTCL) surveillance bias might explain some of the increased risk seen. Patients with psoriasis who present with a newly developed atypical plaque or patch are advised to do a skin biopsy with the possibility of CTCL [176]. This underlines the difficulty in the differentiation of CTCL and psoriasis in some cases; thus, misdiagnosis could potentially also explain some of the increased risk. However, for surveillance bias to be dominating, one would also expect the risk of MM to be increased in patients with psoriasis, which is not the case [15,16]. Moreover, surveillance bias cannot explain the increased risk of some solid and hematologic cancers.
How is safety of dermatology drugs assessed: trials, registries, and spontaneous reporting
Published in Expert Opinion on Drug Safety, 2020
Leila Asfour, Zenas Z.N. Yiu, Richard B. Warren
There are common treatments that have had their adverse effect profile described in mainstream media impacting on how receptive patients are to these treatments and the importance of addressing those particular concerns in consultation. One of the most common examples is the acne treatment, Isotretinoin, and the concern around increased suicide ideation. Apart from case reports, there has not been any clear proof of an association. However, there is a concern about the possibility of a rare idiosyncratic adverse effect that has not been fully delineated[30]. Another example is the topical preparations tacrolimus and pimecrolimus; both often used as second-line options in atopic dermatitis for both adults and children and the concern regarding the association of skin cancer[31]. Parents often enquire regarding this concern[32]. A recent post-authorization study of children and adults in four European population-based databases found their topical use was associated with an increased risk of lymphoma. However, the low absolute risk for lymphoma and cutaneous T-cell lymphoma means that even if the increased risk observed is causal, the excess risk for an individual patient is relatively small [33]. This post-marketing surveillance data and the use of patient databases are vital in updating safety profiles and are highly applicable to clinical practice. Clinicians, therefore, are required to inform patients and advise around these adverse events.