Introduction to Cancer Modeling
Yang Kuang, John D. Nagy, Steffen E. Eikenberry in Introduction to Mathematical Oncology, 2018
Describing cancer as "uncontrolled cell growth," as is frequently done, is a bit like calling a rocket "a stick that moves." Indeed, rockets move and cancers grow without a lot of regulation, but something is obviously amiss. "Cell growth," i.e., cells becoming larger, is not the problem. Cell replication (proliferation) is. But even saying "cancer is uncontrolled cell proliferation" still fails to uniquely characterize cancer because many other diseases such as, elephantiasis, Huntington's disease, Alzheimer's disease, diverticulitis and atherosclerosis to name a few also are characterized by uncontrolled proliferation. Tumor growth models have their historical roots in the work of Ludwig von Bertalanffy and Benjamin Gompertz. Although neither indicated in print any particular interest in tumors, both studied general growth equations that were later successfully applied to actual tumor data, along with many ecological applications. In science, competing theoretical models often are united when someone demonstrates that they are nothing more than special cases of a more global theoretical approach.
Diethylcarbamazine
Urban Hellgren, Orjan Ericsson, Orjan Ericsson, Lars L Gustafsson in Handbook of Drugs for Tropical Parasitic Infections, 1995
Base: MW 199; citrate: MW 391; pKa 7.7. Freely soluble in water. It should be stored in airtight containers and the solutions protected from light. Pharmacology and mechanism of action Diethylcarbamazine (DEC) is a piperazine derivative which was introduced in clinical medicine in 1947. The drug is active against adult and microfilariae forms of Wuchereria bancrofti, Brugia malayi, Brugia timori and Loa loa. Against Onchocerca volvulus, the drug is only effective against the microfilariae. Soon after its administration, it causes rapid disappearance of microfilariae from the blood (lymphatic filariasis) or from the skin (onchocerciasis). Its effect against microfilariae in nodules or in hydroceles and in advanced elephantiasis is minimal (1).
Leontiasis Ossea
Michael E. Mulligan in Classic Radiologic Signs, 2020
Leontiasis is a descriptive term that has been used for at least three different disorders. The first use of the term was for a form of leprosy affecting the facial soft tissues. In this sense, the term has been used since Claudius Galen’s time’ (circa 130–201 ad). Second, the term was used for a type of elephantiasis affecting the soft tissues of the head and neck. Third, leontiasis ossea, was the name given by Rudolf Virchow (1821–1902) to a condition causing hyperostosis of the skull. He felt that the overgrowth of bone matched the elephantiasis of soft tissue and ‘he decided to call these cases leontiasis ossea, not because the bone disease produced a leonine appearance, but because he considered it to be analogous to a disease of the soft parts which did.’ 2 Virchow’s description is based on the study of several skulls, the first one originally described by Marcello Malpighi (1628–1694) in the Opera Posthuma in 1700 2 . Another case known to Virchow, the first with a clinical history, is shown in Figure 2 . Today, we use the term leontiasis ossea primarily to describe the skull changes due to the condition known as fibrous dysplasia ( Figure 1 ). Whether any of the cases studied by Virchow were actually due to fibrous dysplasia is not known. Disorders other than fibrous dysplasia also give rise to leonine changes in facial bones. Among them are Paget’s, renal osteodystrophy and reactive inflammatory bone disease 3 . Figure 1 Anteroposterior (A) and lateral (B) views of the skull showing extreme deformation due to fibrous dysplasia. Case courtesy of Dr Anne Brower Figure 2 Drawing of Fourcade’s case. The patient was his son who died at age 45 in 1767. Reprinted from Knaggs 2 . Leontiasis Ossea. Br. J. Surg., 1923, 11, 347–79 with permission of Blackwell Science Ltd, the publisher
AA amyloidosis as a complication of primary lymphedema
Published in Amyloid, 2014
François Beloncle, Johnny Sayegh, Caroline Eymerit-Morin, Agnès Duveau, Jean-François Augusto
Primary lymphedema is a rare disease caused by a disorder of lymphangiogenesis. Clinical presentation and age at onset are variable. AA amyloidosis is usually due to chronic inflammatory diseases, malignant tumors or less frequently chronic infectious diseases. We report here the first two cases of AA amyloidosis present with renal failure and nephrotic syndrome in patients with primary lymphedema-induced chronic leg ulcers. The first patient was a 62-year-old female who presented with chronic untreated leg ulcers for 8 years secondary to primary lymphedema. A kidney biopsy done for nephrotic syndrome allowed the diagnosis of AA amyloidosis. The second patient was a 54-year-old male who presented with hereditary lymphedema and elephantiasis since the age of 12. A salivary gland biopsy allowed the diagnosis of AA amyloidosis. Renal function deteriorated progressively needing chronic haemodialysis. Chronic leg ulcers have been rarely reported to induce AA amyloidosis. Only five other cases have been reported in the literature, but none of them with chronic lymphedema. We believe that the relation between lymphedema, chronic leg ulcers and AA amyloidosis is underestimated.
Oral bioavailability enhancement of flubendazole by developing nanofibrous solid dosage forms
Published in Drug Development and Industrial Pharmacy, 2017
Tamás Vigh, Balázs Démuth, Attila Balogh, Dorián L. Galata, Ivo Van Assche, Claire Mackie, Monica Vialpando, Ben Van Hove, Petros Psathas, Enikő Borbás, Hajnalka Pataki, Peter Boeykens, György Marosi, Geert Verreck, Zsombor K. Nagy
The bioavailability of the anthelminthic flubendazole was remarkably enhanced in comparison with the pure crystalline drug by developing completely amorphous electrospun nanofibres with a matrix consisting of hydroxypropyl-β-cyclodextrin and polyvinylpyrrolidone. The thus produced formulations can potentially be active against macrofilariae parasites causing tropical diseases, for example, river blindness and elephantiasis, which affect altogether more than a hundred million people worldwide. The bioavailability enhancement was based on the considerably improved dissolution. The release of a dose of 40 mg could be achieved within 15 min. Accordingly, administration of the nanofibrous system ensured an increased plasma concentration profile in rats in contrast to the practically non-absorbable crystalline flubendazole. Furthermore, easy-to-grind fibers could be developed, which enabled compression of easily administrable immediate release tablets.
Filarial parasites in the postgenomic era
Published in Expert Review of Anti-infective Therapy, 2009
Evaluation of: Moreno Y, Geary TG. Stage- and gender-specific proteomic analysis of Brugia malayi excretory–secretory products. PLoS Negl. Trop. Dis. 2(10), e326 (2008). Filarial parasites are able to survive for many years in their host, with suppression of the host’s immune response being one major survival strategy of the parasite. However, knowledge on molecules that induce these pathways is limited. Additionally, molecules that induce inflammation, thereby leading to severe pathology, such as elephantiasis, are also not fully identified. This article assesses the findings of a recently published analysis of stage-specific excretory–secretory proteins by sodium dodecylsulfate-polyacrylamide gel electrophoresis in combination with liquid chromatography–tandem mass spectrometry. In total, 228 proteins with known and unknown functions were identified and compared with genomic, expressed sequence tags and proteomic databases. We discuss the key findings of this article for implications on filarial parasitism, as well as for a potential use for new therapeutics.
Related Knowledge Centers
- Lymphedema
- Vulva
- Lymphatic System
- Scrotum
- Filarial Elephantiasis
- Filariasis
- Podoconiosis