Incidence and associated factors of cetuximab-induced hypersensitivity infusion reactions in 1392 cancer patients treated in four French areas: a possible association with Lyme disease?

BACKGROUND: Previous studies have observed an increased incidence of Cetuximab-induced hypersensitivity infusion reactions (CI-IRs) in the southeastern states of the USA. Tick's bites were suspected of generating cross-reactions between cetuximab and alpha-gal. This study aims was to describe the incidence and associated risk factors of CI-IRs, in the French areas chosen according to their Lyme disease incidence. PATIENTS AND METHODS: A retrospective chart review was conducted on patients that received cetuximab infusion from January 2010 to June 2019 in 4 French areas with different Lyme disease incidence rates. RESULTS: Of 1392 patients, 117 (8.4%) experienced a CI-IR, including 68 severe (grade 3 or 4) reactions (4.9%). This CI-IR incidence was significantly higher in the Lyme disease high-risk area than in the other areas (13.2% versus 7.1%, 8.1% and 6.4%; P = 0.016). Sex (P = 0.53), premedication (P = 0.91), primary cancer location (P = 0.46) and chemotherapy regimen type (P = 0.78) had no impact on CI-IR incidence in the overall population. In the head and neck squamous cell carcinoma (HNSCC) patient subgroup, CI-IRs were significantly more frequent in the high-risk area (16.4% versus 6.7%, 7.1% and 7.0%; P = 0.0015). CONCLUSION: This study suggests that patients treated in the French area with the highest incidence of Lyme disease are at a higher risk of CI-IRs.

[Patients' satisfaction and waiting time in oncology day care centers in Champagne-Ardenne]. / Programme d'évaluation de l'administration des chimiothérapies en hôpital de jour en Champagne-Ardenne (PEACH) : satisfaction et délais d'attente des patients.

AIM: Quality of life of patients suffering from cancer may be influenced by the way healthcare is organized and by patient experiences. Nowadays, chemotherapy is often provided in day care centers. This study aimed to assess patient waiting time and satisfaction in oncology day care centers in Champagne-Ardenne, France. METHODS: This cross-sectional survey involved all patients receiving ambulatory chemotherapy during a one-week period in day care centers of Champagne-Ardenne public and private healthcare institutions participating in the study. Sociodemographic, medical and outpatient data were collected. Patient satisfaction was measured using the Out-Patsat35 questionnaire. RESULTS: Eleven (out of 16) oncology day care centers and 441 patients participated in the study. Most of the patients were women (n=252, 57.1%) and the mean age was 61±12 years. The mean satisfaction score was 82±14 (out of 100) and the mean waiting time between the assigned appointment time and administration of chemotherapy was 97±60 min. CONCLUSION: This study has shown that waiting times are important. However, patients are satisfied with the healthcare organization, especially regarding nursing support. Early preparation of chemotherapy could improve these parameters.

THOR-05F biofidelity evaluation in reclined and upright seated postures subjected to frontal crash pulses.

The THOR 5th percentile female dummy (THOR-05F) was evaluated for two seating postures/positions in frontal impacts using a generic automotive seat environment. The conditions included 2 crash pulses: a 15 km/h test that utilized 4.5 g acceleration and a 3-point restraint with 2 kN load limiter, and a 32 km/h test that utilized 9.5 g acceleration and a 3-point restraint with a 4.5 kN load limiter and pretensioner, and two seatback angles: 25°, a nominal upright posture, and 45°, a moderate reclined posture. The BRS scores were calculated using the NHTSA BioRank method. Overall biofidelity rating was consider excellent for both seating postures. This evaluation provides an understanding of the THOR-05F response and biofidelity evaluation of the ATD in two seating postures (nominal and reclined). This is essential in the assessment and development of safety measures in emerging ADS-equipped vehicles.

[Oral ulcerations]. / Les ulcérations de la bouche.

Oral ulcerations are frequent lesions resulting from numerous different causes. A precise anamnesis is mandatory to direct towards the diagnosis. It includes the type of the earliest lesion (blister/vesicle or ulceration), the number of lesions (isolated or numerous), the complaints (painful or asymptomatic), the disease evolution (acute, chronic, recurrent), the duration of the ulceration (a few hours, days, weeks, months, years...), the presence of adenopathies and/or the association with clinical lesions on other mucous membranes, on skin, on nails or on scalp. A traumatism or a drug reaction are the first aetiologies to be excluded. Chronic enteropathies or lupus erythematosus or other systemic diseases, especially those leading to immunosuppression, can be responsible for oral ulcerations. These diseases must be diagnosed and treated to obtain an improvement of the oral lesions. Laboratory studies such as microbiological isolation, serology or biopsy, are performed in accordance with the suspected diagnosis resulting from anamnesis and physical examination. Aphthous stomatitis and oral herpes infection present similar features such as symptomatology, recurrences, trigger factors, etc. Differential diagnosis is mandatory to treat correctly the disease. It is easier if the primary lesion (vesicle or ulceration) is observed or if herpes simplex virus is yielded. Oral blisters are uncommon; they especially concern erythema multiforme and bullous auto-immune diseases. A single ulceration directs towards a diagnosis of cancer or chancre. Lichen planus is a frequent disease of the oral mucous membrane with numerous clinical features: erosive and ulcerated lesions are often observed. In all cases, a symptomatic treatment is necessary against pain to permit nutrition, hydratation and good speech. An etiologic treatment is associated as soon as possible.

Human G protein-coupled receptor GPR-9-6/CC chemokine receptor 9 is selectively expressed on intestinal homing T lymphocytes, mucosal lymphocytes, and thymocytes and is required for thymus-expressed chemokine-mediated chemotaxis.

TECK (thymus-expressed chemokine), a recently described CC chemokine expressed in thymus and small intestine, was found to mediate chemotaxis of human G protein-coupled receptor GPR-9-6/L1.2 transfectants. This activity was blocked by anti-GPR-9-6 monoclonal antibody (mAb) 3C3. GPR-9-6 is expressed on a subset of memory alpha4beta7(high) intestinal trafficking CD4 and CD8 lymphocytes. In addition, all intestinal lamina propria and intraepithelial lymphocytes express GPR-9-6. In contrast, GPR-9-6 is not displayed on cutaneous lymphocyte antigen-positive (CLA(+)) memory CD4 and CD8 lymphocytes, which traffic to skin inflammatory sites, or on other systemic alpha4beta7(-)CLA(-) memory CD4/CD8 lymphocytes. The majority of thymocytes also express GPR-9-6, but natural killer cells, monocytes, eosinophils, basophils, and neutrophils are GPR-9-6 negative. Transcripts of GPR-9-6 and TECK are present in both small intestine and thymus. Importantly, the expression profile of GPR-9-6 correlates with migration to TECK of blood T lymphocytes and thymocytes. As migration of these cells is blocked by anti-GPR-9-6 mAb 3C3, we conclude that GPR-9-6 is the principal chemokine receptor for TECK. In agreement with the nomenclature rules for chemokine receptors, we propose the designation CCR-9 for GPR-9-6. The selective expression of TECK and GPR-9-6 in thymus and small intestine implies a dual role for GPR-9-6/CCR-9, both in T cell development and the mucosal immune response.

[Allergies to dental metals. Titanium: a new allergen]. / Les allergies aux métaux dentaires. Un allergène émergent: le titane.

Oral allergies are underdiagnosed by dental health professionals. Patients with an oral allergy complain of various symptoms such as burning or tingling sensations, with or without oral dryness or loss of taste, or of more general symptoms such as headache, dyspepsia, asthenia, arthralgia, myalgia. The signs of oral allergy include erythema, labial oedema or purpuric patches on the palate, oral ulcers, gingivitis, geographical tongue, angular cheilitis, perioral eczematous eruption, or lichenoid reactions localized on the oral mucosa. There is an increase in the prevalence of oral allergies to metals used in dental materials. Allergy to gold included in dental prosthesis has been well documented since the years eighties. Recently, titanium, used in orthopedic devices and oral implants, considered as an inert material, can induce toxicity or allergic type I or IV reactions. These reactions to titanium could be responsible for unexplained successive failure cases of dental implants in some patients (named "cluster patients"). The risk of an allergy to titanium is increased in patients who are allergic to other metals. In these patients, an evaluation of allergy is recommended, in order to exclude any problem with titanium medical devices. We stress the importance of a multidisciplinary approach to take into account patients with an oral allergy, with participation of specialists from dental and dermatologic fields.

[How to diagnose and how to treat diseases of the genital mucosa?]. / Reconnaître et traiter les lesions des muqueuses génitales féminines.

The genital area in women is covered by a keratinized squamous stratified epithelium outside the body (vulva), and a non keratinized epithelium inside the body (vagina). These characteristics can have an effect on the clinical aspects of the diseases and/or on the choice of the treatment. Symptoms (itching, pain, vaginal discharge), preferential localisation of skin diseases (psoriasis, lichen planus, lichen sclerosus, atopic dermatitis and allergic contact dermatitis, irritative dermatitis) and the aspect of primary lesions are to be investigated. The implication of this region in sexual activity places it at risk of sexually transmitted diseases (STD's) and dyspareunia. These have numerous causes that have to be sought and taken care of, often by multidisciplinary teams. After a careful history and clinical examination, additional tests allow to exclude infections or confirm a skin condition or neoplasia by a skin biopsy. If contact dermatitis is suspected, specific allergy testing is done. Treatment starts with correction of harmful habits (excessive use of soaps, inappropriate cosmetic products,...) that add to the local irritation. Patients are then reassured of common misconception regarding cancer, STD's and fertility. In the vast majority of cases, the treatment will target an infection (fungal, bacterial, STD's), will relieve irritation by the use of local immunosuppressant drugs (local corticosteroids) and/or relief itching symptoms with anti-histamine drugs.

[Economic evaluation of at home subcutaneous and intravenous immunoglobulin substitution]. / Etude comparative du coût du traitement à domicile des immunoglobulines intraveineuses ou sous-cutanées à visée substitutive.

BACKGROUND: Intravenous (IV) and subcutaneous (SC) immunoglobulin (Ig) administration is a safe and an efficacious treatment in patients with IgG deficiency. Home administration of IV Ig and SC Ig has recently been approved in France. Most of the patients treated in hospital ask for home treatment. Some patients prefer monthly IV administration, others weekly SC administration. MATERIAL AND METHODS: We evaluated in details the cost of both of these practices. We currently use electric pumps for both IV and SC administration which are fixed to the patient giving complete freedom and mobility. RESULTS: For 20 g administrated per 4 week, the total cost of home treatment is 1,518 euro with SC Ig and 1,033 euro with IV Ig. For 40 g administrated per 4 week, the total cost of home treatment is 2,507 euro to 2,729 euro with SC Ig and 2,034 euro with IV Ig. The difference is mainly explained by the cost of renting the electric pumps and by the cost of furniture for SC administration. The choice of home Ig substitution must be given to all patient receiving treatment in hospital. CONCLUSIONS: Home IV and home SC perfusions are two possible options each different with there own advantages and disadvantages. The cost of each procedure must be known by the medical staff.

Characteristics of megakaryocyte colony formation in normal individuals and in primary thrombocythemia: studies using an optimal cloning system.

Colony formation by megakaryocyte (MK) progenitors was studied in 36 normal individuals and in 26 patients with primary thrombocythemia (PT) using an improved plasma clot cloning system. MK colonies were identified by immunoperoxidase staining using a monoclonal antibody against human platelet glycoprotein IIb/IIIa complex. In normal individuals, a frequency of 194 +/- 23 MK colony-forming units (CFU-MK) per 5 X 10(5) bone marrow nonadherent mononuclear cells and 11 +/- 4 CFU-MK per 5 X 10(5) blood mononuclear cells was found. These CFU-MK grew as large (greater than 20 cells), mean (11-20 cells), small (3-10 cells), or mix-MK colonies (at least two MK) that comprised 15%, 23%, 62%, or 5% of all MK colonies in bone marrow and 0%, 8%, 92%, or 1% in peripheral blood, respectively. In PT, several abnormalities of MK colony formation were observed: 1) increased circulating CFU-MK numbers, 2) increased mix-MK colony formation, 3) spontaneous MK colony formation without phytohemagglutinin-stimulated leukocyte-conditioned medium and normal serum, 4) decreased proportion of larger MK colonies (greater than 11 cells) in PT bone marrow, and 5) failure of PT plasma or serum to stimulate MK colony formation by normal marrow cells in a normal fashion. These results indicate some of the characteristics of quantitative and qualitative abnormalities of in vitro megakaryocytopoiesis in PT.

[Genital herpes]. / L'herpès génital.

In developed countries, genital herpes is, together with papillomavirus infections, among the most common sexually transmitted diseases. HSV is a dormant virus causing lifelong infection and recurring with or without clinical symptoms. Exposure to lesions and to asymptomatic viral shedding result in transmission. Thus, in most cases, finding the exact path of viral transmission is impossible. The diagnosis is often clinical: classic lesion presentation and typical localised recurrences. The confirmation of the diagnosis is obtained by virus isolation, the most sensitive method is PCR but viral culture techniques are the most widely used. Today, the nucleoside analog antivirals (aciclovir, valacicovir, famciclovir, penciclovir), are the only efficient and well tolerated treatments for genital herpes. The virus resistance to these molecules in immunocompetent patients is very low and has not increased since their introduction. Thus, for these patients, treatment failure is generally due to low bioavailability which is resolved by increasing doses. Ideally a vaccine against herpes should be prophylactic (preventing primary infection) and therapeutic (preventing recurrences). None is available today despite intensive research for the past two decades.

Spreading of psoriatic plaques: alteration of epidermal differentiation precedes capillary leakiness and anomalies in vascular morphology.

To approach the temporal relationship between alterations in keratinization and capillary leakiness in psoriasis, we studied the topography of these anomalies in spreading psoriatic lesions. Histological and immunohistochemical studies were performed on skin biopsies obtained from normal individuals and from psoriatic patients. In the latter case, biopsies were taken in uninvolved skin, in the center of lesions, and at the edge of evolving plaques (spanning uninvolved and involved skin). Alterations in epidermal differentiation were assessed by the distribution of filagrin, involucrin, and epidermal membrane-bound transglutaminase. Capillary leakiness was evaluated by the abundance of plasma proteins such as albumin, fibrinogen, and immunoglobulin G within the epidermis. Typical alterations of epidermal differentiation were already obvious at the edge of the lesions, in areas devoid of vessel abnormalities and leakiness, or significant cellular infiltration. These results strongly suggest that, during the formation of a psoriatic plaque, defects in keratinocyte differentiation precede the development of vascular anomalies.

Overexpression of Bcl-2 in Kaposi's sarcoma-derived cells.

The pathogenesis of Kaposi's sarcoma (KS), a tumor of probable vascular origin, remains an enigma. It is still unclear whether KS is a true malignancy or whether it represents a reactive polyclonal process. Using both an immunohistochemical and an immunoblot approach, we found that cells derived from KS lesions express significant levels of Bcl-2, a protein known to prolong cellular viability and to antagonize apoptosis. Bcl-2 expression was found in AIDS-related KS-derived cells, as well as in cells derived from iatrogenic and sporadic KS, indicating that Bcl-2 upregulation may be important in the pathogenesis of KS regardless of its epidemiologic form. By contrast, fibroblasts and dermal microvascular endothelial, cells which are the probable vascular progenitors of KS cells, expressed low levels of Bcl-2. The expression of Bcl-2 in KS-derived cells was associated with a long-term survival in serum-deprived conditions, a situation that has been shown to induce apoptosis in various cell types. Incubation of fibroblasts or of dermal microvascular endothelial cells with KS cell-free supernatants did not enhance Bcl-2 expression, suggesting that Bcl-2 expression is not mediated by an agent released by KS cells. Analogously, KS supernatants failed to promote the viability of fibroblasts and of dermal microvascular endothelial cells cultured in serum-free conditions. Our findings suggest that the spindle cells derived from KS have a survival advantage and may adequately represent the tumor cells of KS.

Early- and late-stage Kaposi's sarcoma-derived cells but not activated endothelial cells can invade de-epidermized dermis.

Whether Kaposi's sarcoma is a true neoplasm or a reactive endothelial cell outgrowth triggered by inflammatory cytokines remains unclear. In this study, we investigated the differential invasive properties of activated endothelial cells and Kaposi's sarcoma cells in a model of de-epidermized dermis, supplying the cells with matrix barriers similar to those found in vivo. Cells derived from early "patch-stage" and from late "nodular-stage" Kaposi's sarcoma lesions exhibited similar invasive properties, which indicates that cells with an invasive potential are present in the early stages of tumor development. Slow accumulation of the cells into the extracellular matrix, together with a low proliferation index and with expression of anti-apoptotic proteins, suggest that the progression of Kaposi's sarcoma may be related to escape from cell death rather than to increased proliferation. The Kaposi's sarcoma-Y1 cell line, which is tumorigenic in nude mice, also exhibited invasive properties. By contrast to the Kaposi's sarcoma-derived spindle cells, however, which were scattered between the collagen bundles, the Kaposi's sarcoma-Y1 cell population had a higher proliferation index and displayed a multilayer arrangement. Inflammatory cytokines and Kaposi's sarcoma cell supernatant could activate and stimulate the growth of human dermal microvascular endothelial cell, but could not induce their invasion in this model, showing that activated endothelial cells do not fit all the requirements to traverse the various barriers found in the dermal extracellular matrix. These results confer to Kaposi's sarcoma cells a tumor phenotype and suggest that the in vivo dominant endothelial cell population represents a reactive hyperplasia rather than the true tumor process.

Renewal and differentiation of keratinocytes cultured on dead de-epidermalized dermis.

Human keratinocytes grown at an air-liquid interface on dead de-epidermalized dermis exhibit a pattern of organization similar to that seen in vivo. Cell renewal is limited to the basal layer. The cell cycle time determined after 7 days of culture, using a percentage labelled mitoses (PLM) technique, was about 15 h. This result is comparable with published data for cultivated keratinocytes but is shorter than the parameter proposed for epidermis in vivo. Appearance of labelled cells in the granular layer was observed 4 days after pulse labelling. Despite this high cell renewal, a normal cell differentiation with expression of various keratinization markers was maintained.

FB1, a monoclonal antibody reacting with a keratin 14 epitope, stains only a small subset of psoriatic basal keratinocytes.

A murine monoclonal antibody, FB1, reacted with the basal keratinocytes of human stratified epithelia. One-dimensional and two-dimensional immunoblotting assays, performed on keratins extracted from HaCat cells and normal human keratinocytes, showed that FB1 recognizes K14. When LL002, another K14 monoclonal antibody is added, the FB1 stained area in the 2D-immunoblot seems to cover a fraction of the LL002 spot. Immunohistochemical data obtained from studies on normal human tissues supported the K14 specificity of FB1, but when compared with two other monoclonal antibodies, LL002 and RCK107 reacting with K14, some differences appeared. These differences were mainly seen in sweat glands, hair follicles, psoriatic epidermis and salivary glands. In psoriatic epidermis, FB1 showed a heterogeneous pattern of staining of the basal cell compartment. Intense reactivity was only observed at the bottom of the rete ridges. Staining diminished and finally disappeared in the basal cells above the dermal papillae. This observation supports the view that an increased germinative cell population in psoriasis involves a partially differentiated amplifying compartment in which the number of cell divisions is increased.

Diffusive and convective solute clearances during continuous renal replacement therapy at various dialysate and ultrafiltration flow rates.

Clearances of several solutes (urea, creatinine, phosphate, urates, beta(2)-microglobulin [beta(2)-M]) were measured during venovenous continuous renal replacement therapy (CRRT) at various ultrafiltration (Q(UF); 0 to 2 L/h) and dialysate flow rates (Q(D); 0 to 2.5 L/h). Preset Multiflow-60 and Multiflow-100 hollow-fiber dialysers (M-60 and M-100; Hospal-Gambro, St-Leonard, Canada) were compared (five patients for each type). First, we evaluated the impact of predilution on convective clearances: a progressive decrease in patient clearances, similar for both filters, was observed, reaching a maximum of 15%, 18%, and 19% for urea, urates, and creatinine, respectively, with predilution at a Q(UF) of 2 L/h. Second, we compared convective and diffusive clearances. Because effluent to plasma ratio (E/P) remained at 1 for small solutes (urea, creatinine, phosphate, urates) during convection, clearances were equal to the effluent rate for both dialyzers. However, we observed greater diffusive clearances for small molecules with M-100 than with M-60 at a Q(D) of 1.5 to 2.5 L/h, the difference being more significant as molecular weight increased. For beta(2)-M, diffusive clearance was very low and rapidly reached a plateau of 8 and 12 mL/min for M-60 and M-100, respectively, at a Q(D) greater than 1.5 L/h. Convective clearances for beta(2)-M increased nonlinearly up to 20 +/- 2 mL/min at a progressively greater Q(UF) (from 0.5 to 2 L/h) for both M-60 and M-100. This nonlinear increase was attributed to an increase of almost 40% in E/P for beta(2)-M from a Q(UF) of 0.5 to 2 L/h. Third, the interaction between convection and diffusion was assessed by measuring solute clearances at a fixed Q(UF) (1 and 2 L/h) and variable Q(D) (0.5 to 2.5 L/h). For small molecules, no significant interaction between convection and diffusion was noticed with M-100, whereas only a small interaction was noticed with M-60. However, for beta(2)-M, the addition of diffusion (Q(D), 0.5 to 2.5 L/h) did not result in any significant increase in total clearances over convective clearances for M-60 and M-100. This observation suggests that the diffusive clearances for beta(2)-M observed with M-60 and M-100 at a Q(UF) of 0 L/h and at various Q(D) probably occurs by convective fluxes across the membrane. These results demonstrate that convection is more efficient than diffusion in removing mixed-molecular-weight solutes during CRRT.

Ion-molecule reactions in mixtures of trimethylaluminum and methylamines.

The ion-molecule reactions of mixtures of trimethylaluminum and methylamines, to serve as a model system for group 13-15 semiconductor fabrication, were examined by using Fourier transform ion cyclotron resonance mass spectrometry. Sequential ion-molecule reactions leading to formation of multiple adduets were observed for each of the reactant mixtures investigated. Collision-induced dissociation was used to probe the adduct structures. There is evidence for hydrogen bonding between the amines and aluminum in most of the adducts studied. Rearrangement of the aluminum/nitrogen skeletons was not observed, although the aluminum/nitrogen bonds appear to be relatively strong, so that stable adducts can be formed. The monomethylamine and dimethylamine readily produce gas-phase neutral adducts with trimethylaluminum, which can be related to the basicities of the methylamines.

PCR assay fails to detect molluscum contagiosum virus-related sequences in AIDS-related Kaposi's sarcoma.

Previous PCR-based studies have demonstrated the presence of various viral DNA or RNA sequences in Kaposi's sarcoma (KS) tissues. To date, only human herpesvirus 8 (HHV-8) DNA sequences are found consistently in KS. The putative role of this agent in KS pathogenesis remains, however, to be determined; HHV-8 could infect populations endemically and could be reactivated in patients with KS. A close association between AIDS-related KS and molluscum contagiosum occurrence was found and this study was conducted primarily to search for the presence of molluscum contagiosum virus DNA sequences in KS. Frozen KS samples were examined for the presence of both HHV-8 and molluscum contagiosum virus DNA sequences by PCR. Despite a high rate of co-infection, no molluscum contagiosum virus (MCV) DNA sequence could be found in the KS samples whereas HHV-8 was uniformly detected. These results suggest that the high prevalence of MCV in AIDS patients with KS relies on a mode of transmission common for HHV-8 and molluscum contagiosum virus rather than on a multiviral etiology of KS. They may also indicate a particular susceptibility of the host to viral reactivation. If this is so, the failure to detect MCV DNA sequences in KS tissues by PCR indicates that locally produced or released cyotokines are not involved in the latter process.

Iron induces Bcl-2 expression in human dermal microvascular endothelial cells.

Iron is suspected to be involved in the induction and/or progression of various human tumors. The present study was designed to investigate the effects of iron on endothelial cells, keeping in mind that the homeostasis of microvessels plays a critical role in neo-angiogenesis. Applying a model of human dermal microvascular endothelial cell terminal differentiation and death induced by serum deprivation, we found that iron salts (iron chloride and ferric nitrilotriacetate) provided a survival advantage to endothelial cells. Using immunohistochemistry and Western Blot analysis, we found that the extended cellular life span induced by iron was paralleled by an increase of Bcl-2 protein expression. Taken together, these observations suggest that iron may give a survival advantage to endothelial cells and represent a novel mechanism through which iron may contribute to tumorigenesis.

In vitro sensitivity of Kaposi's sarcoma cells to various chemotherapeutic agents including acyclic nucleoside phosphonates.

The involvement of a viral agent in the pathogenesis of Kaposi's sarcoma (KS) points to antiviral agents as possible therapeutic and/or prophylactic options in the management of the disease. In the present study we investigated the antiproliferative effects of various chemotherapeutic agents, including acyclic nucleoside phosphonates, on the growth of KS-derived cells. Nested PCR amplification demonstrated that these cells do not contain human herpesvirus 8 (HHV-8) DNA sequences. The cytotoxicity of the chemotherapeutic compounds was less pronounced in KS cells than in human dermal microvascular endothelial cells, which are considered to be the normal counterpart of KS cells. Stimulation of KS cells with basic fibroblast growth factor (bFGF) and correction of the IC50 values by the doubling times revealed that the apparent chemotherapeutic resistance of KS cells could mainly be attributed to the long doubling times of these cells. bFGF-stimulated KS cells still exhibited no particular sensitivity to the acyclic nucleoside phosphonates whose activity extends to HHV-8, which is consistent with the absence of linear HHV-8 DNA synthesis in these cells. Our data suggest that neither anti-cancer agents nor antiviral agents such as the acyclic nucleoside phosphonates can discriminate efficiently between KS cells and normal endothelial cells.