30 research outputs found
Photoactivatable prodrugs of antimelanoma agent Vemurafenib
In this study, we report on novel
photoactivatable caged prodrugs
of vemurafenib. This kinase inhibitor was the first approved drug
for the personalized treatment of BRAF-mutated melanoma and showed
impressive results in clinical studies. However, the occurrence of
severe side effects and drug resistance illustrates the urgent need
for innovative therapeutic approaches. To conquer these limitations,
we implemented photoremovable protecting groups into vemurafenib.
In general, this caging concept provides spatial and temporal control
over the activation of molecules triggered by ultraviolet light. Thus,
higher inhibitor concentrations in tumor tissues might be reached
with less systemic effects. Our study describes the first development
of caged vemurafenib prodrugs useful as pharmacological tools. We
investigated their photochemical characteristics and photoactivation. <i>In vitro</i> evaluation proved the intended loss-of-function
and the light-dependent recovery of efficacy in kinase and cellular
assays. The reported vemurafenib photo prodrugs represent a powerful
biological tool for novel pharmacological approaches in cancer research
Hairy cell lymphoma: a potentially under-recognized entity
Hairy cell leukemia (HCL) is a low grade B-cell lymphoproliferative disorder that typically presents with splenomegaly, cytopenias, and diffuse bone marrow infiltration. There have been few cases in the literature of HCL presenting as lymphomas in extra-nodal locations, such as soft tissues and bones without circulating leukemic cells, splenomegaly, or iliac crest bone marrow involvement. We present an additional case presenting as a thoracic mass, and discuss potential diagnostic pitfalls and management of these rare cases
Anaesthesia in Congenital Facial Anomalies in a Rural Set up of a Developing Country
Background: India has an estimated backlog of
1000000 cleft patients. A total of 35000 new cleft
patients are born each year. With the capacity to
operate on approximately 50000 patients each year
only 15000 patients from the national backlog can be
operated upon each year if capability is not augmented.
Objectives: To reach the population at large we
meticulously planned an out-reach programme and
operated on patients even in rural set ups with lack of
modern facilities. We operated on patients at sub
divisional centres, where apparatus for providing
sevoflurane was not available. Institutional Ethical
clearance was taken before conduction of the study.
Patients who required prolonged surgery were taken to
the tertiary centre. Working ventilators were also not
available at peripheral centres. Materials and
Methods: This interventional study was carried in a
time span of four years on nineteen hundred and nine
patients, after taking approval from the Institutional
Ethical Committee. Patients were screened and some
were operated at rural centers and others at a tertiary
care centre. Patients who could not afford to come to
the tertiary care centre were operated at different rural
centers. Informed consent was taken. Results: There
were 1909 patients with Congenital Facial Anomalies
(CFA) over four years period out of which 918 patients
were of either unilateral or bilateral cleft lip. They were
successfully operated at rural health centers with
limited facilities. This could reduce the total load of
surgeries for CFA at tertiary care hospital ensuring safe
surgeries for all with CFA for all age groups and both genders.No mortality was recorded and post operative
complications consisted of nausea and vomiting, three
had delayed recovery and one had laryngospasm.
Conclusion: Outreach programmes can increase the
efficacy of Smile Train Project and effective screening
of patients before surgery can result in fruitful
outcomes even in a rural set up with lack of modern
anaesthetic facilities
High grade leiomyosarcoma mimicking a recurrent angiomyxoma in the perineum
Perineal leiomyosarcoma is an extremely rare and aggressive cancer with a high metastatic potential and no defined standard treatment. There are only a few (six) reported cases in the literature. We report the case of a 67-year-old woman with a perineal leiomyosarcoma arising at the same site of a previously resected superficial angiomyxoma. Initially, she was treated for a presumptive recurrence of angiomyxoma. As she did not respond to medical therapy, she underwent repeat surgical excision. Pathology revealed a high grade leiomyosarcoma, histologically strikingly distinct from the initial diagnosis. She received adjuvant local radiation therapy, and remains without evidence of recurrent disease 36 months after completion of all therapy. This is the first reported case of a high grade perineal leiomyosarcoma originating at the same site as a resected benign superficial angiomyxoma. Our case emphasizes the necessity of a prompt histological diagnosis in cases of presumed recurrent perineal angiomyxoma
Supplementary Material for: Pharmacoeconomic Implications of Lenalidomide Maintenance Therapy in Multiple Myeloma
We compared the three arms of the MM-015 randomized phase III clinical trial [melphalan and prednisone (MP), MP plus lenalidomide (MPR), and MPR plus lenalidomide maintenance (MPR-R)] to determine whether the addition of lenalidomide maintenance therapy for primary treatment of multiple myeloma is cost-effective. We used progression-free survival and adverse event data from the MM-015 study for the analysis. Two novel measures of cost-effectiveness termed the Average Cumulative Cost per Patient (ACCP) and the Average Cumulative Cost per Progression-Free Survivor (ACCPFS) were developed for the purpose of this analysis. The ACCP of MP was USD 18,218, compared to USD 167,862 for MPR and USD 309,173 for MPR-R. The ACCPFS was highest with MPR at USD 1,555,443, while MP was USD 313,592 and MPR-R was USD 690,111. MPR-R is superior to MPR in terms of preventing the first progression after initial therapy. However, the addition of lenalidomide to MP in the induction and also in the maintenance setting leads to significant costs