Amivantamab plus lazertinib versus osimertinib in first-line EGFR-mutant advanced non-small-cell lung cancer with biomarkers of high-risk disease: a secondary analysis from MARIPOSA.

BACKGROUND: Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups. PATIENTS AND METHODS: This analysis included patients with treatment-naive, EGFR-mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR). RESULTS: Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR-mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]. CONCLUSIONS: Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR-mutant advanced NSCLC.

HLJ1 is an endogenous Src inhibitor suppressing cancer progression through dual mechanisms.

HLJ1 (DNAJB4), a DNAJ/Hsp40 chaperone, has emerged as a novel prognostic marker in lung cancers; however, the molecular contribution and functionality in neoplastic diseases remain to be established. This study demonstrated that HLJ1 inhibits epithelial-mesenchymal transition in vitro and reduces lung cancer metastasis in vivo. Using shRNA silencing and ectopic expression of HLJ1, we found that HLJ1 not only suppresses catalytic activity of Src but also downregulates the formation of oncogenic complexes associated with the EGFR, FAK and STAT3 signaling pathways. A screen of specimens from HLJ1-knockout mice and lung cancer patients validated that HLJ1 expression is inversely correlated with Src activity. Mechanistically, HLJ1 protein directly bound to catalytic and protein-binding domains of Src through its amino acid Y172 and the P301/P304 motif. Following Src-induced HLJ1 phosphorylation at Y172, HLJ1-Src interaction was elevated, resulting in Src inhibition and malignancy suppression. Interestingly, both Src-binding regions also occurred in other DNAJB family members and contributed to anti-invasive activities of DNAJB proteins. We conclude that HLJ1 is an endogenous Src inhibitor that can suppress cancer metastasis through complex interacting mechanisms. This HLJ1-Src complex might provide a promising molecular model for developing new anticancer strategies.

Pymetrozine causes a nontarget pest, the Colorado potato beetle (Coleoptera: Chrysomelidae), to leave potato plants.

Pymetrozine is a selective insecticide that targets aphids. Published assessments of the effects of pymetrozine on nontarget organisms focus mainly on predatory insects, and they rarely indicate toxicity. In a laboratory bioassay, survival of Colorado potato beetle, Leptinotarsa decemlineata (Say) (Coleoptera: Chrysomelidae), larvae was not affected by pymetrozine exposure. We subsequently used pymetrozine to implement low-aphid-density treatments in a field experiment that involved separate manipulations of Colorado potato beetle density. Unexpectedly, the addition of Colorado potato beetle adults and eggs did not increase the densities of Colorado potato beetle larvae in plots that were sprayed with pymetrozine (applied with water and an adjuvant). In control plots sprayed with water and adjuvant (without pymetrozine), addition of Colorado potato beetles increased densities of their larvae. Data collected on a smaller scale suggest that a behavioral mechanism underlies the population-level pattern: Colorado potato beetle larvae become more active and are less likely to remain on a host plant after exposure to pymetrozine. Thus, potato, Solanum tuberosum L., growers who use pymetrozine against aphids also might benefit in terms of Colorado potato beetle control.

Clinical patterns among invasive pulmonary aspergillosis patients with and without recent intensive immunosuppressive therapy.

BACKGROUND AND PURPOSE: Invasive pulmonary aspergillosis (IPA) is usually an acute life-threatening infection in cancer patients receiving chemotherapy and in organ transplant recipients receiving immunosuppressive therapy. In some immunocompetent patients, IPA has a chronic and indolent clinical course. We compared the clinical patterns among IPA patients who had received recent intensive immunosuppressive therapy (RIIT) and those who had not (N-RIIT). METHODS: We reviewed the medical records of patients with a diagnosis of IPA made between 1992 and 1999. RIIT was defined as chemotherapy or high-dose corticosteroid therapy (at least 500 mg/d methylprednisolone, or equivalent, for at least 3 d) within 2 weeks before the onset of symptoms. RIIT patients were divided into those with and without malignancy. We compared clinical characteristics including age, sex, chest image patterns, diagnostic methods, culture results, treatment conditions, mortality, and recurrence rate in IPA patients: RIIT versus N-RIIT, and RIIT with and without malignancy. RESULTS: A total of 24 patients with IPA, 17 patients who had received RIIT and seven patients who had not (N-RIIT), were included. In the RIIT group, 11 patients had malignancy and six did not. No significant differences in gender, chest image patterns, diagnostic methods, and culture results were found between the RIIT and N-RIIT groups. The N-RIIT group was older and was treated significantly later after the onset of symptoms than the RIIT group (mean +/- standard deviation, SD, 89.43 +/- 129.47 vs 9.70 +/- 9.33 d, p = 0.018). Only one of the seven N-RIIT patients died, while nine of the 17 RIIT patients died (p = 0.08). Among the RIIT patients, five of the six without malignancy died, while four of the 11 patients with malignancy died. IPA recurred in seven of the eight RIIT patients, all of whom had malignancy, but in none of the six N-RIIT patients during a similar follow-up period (mean +/- SD, 16.3 +/- 18.9 vs 27.0 +/- 54.5 mo, p = 0.505). CONCLUSIONS: No differences were noted in image and culture studies between RIIT and N-RIIT IPA patients. RIIT IPA patients had acute and fulminant clinical courses, especially patients without malignancy, even though they received treatment with a mean duration of about 10 days starting from the onset of symptoms. All patients with malignancy undergoing further chemotherapy had recurrence of IPA. N-RIIT IPA patients had chronic clinical courses, a trend of lower mortality rate even with delayed diagnosis, and no recurrence.

Isokinetic elbow joint torques estimation from surface EMG and joint kinematic data: using an artificial neural network model.

Because the relations between electromyographic signal (EMG) and anisometric joint torque remain unpredictable, the aim of this study was to determine the relations between the EMG activity and the isokinetic elbow joint torque via an artificial neural network (ANN) model. This 3-layer feed-forward network was constructed using an error back-propagation algorithm with an adaptive learning rate. The experimental validation was achieved by rectified, low-pass filtered EMG signals from the representative muscles, joint angle and joint angular velocity and measured torque. Learning with a limited set of examples allowed accurate prediction of isokinetic joint torque from novel EMG activities, joint position, joint angular velocity. Sensitivity analysis of the hidden node numbers during the learning and testing phases demonstrated that the choice of numbers of hidden node was not critical except at extreme values of those parameters. Model predictions were well correlated with the experimental data (the mean root-mean-square-difference and correlation coefficient gamma in learning were 0.0290 and 0.998, respectively, and in three different speed testings were 0.1413 and 0.900, respectively). These results suggested that an ANN model can represent the relations between EMG and joint torque/moment in human isokinetic movements. The effect of different adjacent electrode sites was also evaluated and showed the location of electrodes was very important to produce errors in the ANN model.

Partitioning in situ total spectral absorption by use of moored spectral absorption-attenuation meters.

High-temporal-resolution spectral absorption data were acquired by use of one bottom-mounted (approximately 68-m) and three moored spectral absorption and attenuation meters (ac-9 meters at 14, 37, and 52 m) on the Middle Atlantic Bight continental shelf during the fall 1996 period of the Coastal Mixing and Optics experiment. We employed a previously published spectral absorption model with the data to partition total absorption into absorption by water, phytoplankton, detritus, and gelbstoff (dissolved matter). We validated the model by comparing its results against coincident in vivo absorption coefficients derived from discrete bottle samples. Correlations between modeled and in vivo spectra range from 0.873 to 0.998. We optimized these correlations to determine the model parameters. These parameters could not be determined solely from the moored ac-9 results. Therefore a separate set of absorption measurements (from discrete bottle samples) was necessary to permit values for the model parameters to be determined. Model results allow us to separate particulate and dissolved components of absorption and to examine the temporal variability and the vertical distributions and concentrations of each component, given the total absorption in the water column.

Encoding of three-dimensional structure-from-motion by primate area MT neurons.

We see the world as three-dimensional, but because the retinal image is flat, we must derive the third dimension, depth, from two-dimensional cues. Image movement provides one of the most potent cues for depth. For example, the shadow of a contorted wire appears flat when the wire is stationary, but rotating the wire causes motion in the shadow, which suddenly appears three-dimensional. The neural mechanism of this effect, known as 'structure-from-motion', has not been discovered. Here we study cortical area MT, a primate region that is involved in visual motion perception. Two rhesus monkeys were trained to fixate their gaze while viewing two-dimensional projections of transparent, revolving cylinders. These stimuli appear to be three-dimensional, but the surface order perceived (front as opposed to back) tends to reverse spontaneously. These reversals occur because the stimulus does not specify which surface is in front or at the back. Monkeys reported which surface order they perceived after viewing the stimulus. In many of the neurons tested, there was a reproducible change in activity that coincided with reversals of the perceived surface order, even though the stimulus remained identical. This suggests that area MT has a basic role in structure-from-motion perception.

Applying fuzzy logic to control cycling movement induced by functional electrical stimulation.

This study examines the design of a rational stimulation pattern for electrical stimulation and a robust closed-loop control scheme to improve cycling system efficacy for subjects with paraplegia. The stimulation patterns were designed by analyzing gravitation potential needed for the cycling movement of the lower limbs against a frictionless cycling ergometer and the response delay of electrically stimulated muscles. To simplify the cycling control system, the stimulation patterns were fixed and only the single gain of the stimulation patterns was adjusted via a feedback control algorithm. To circumvent the complexity involved with exactly modeling a stimulated muscle and cycling ergometer, a model-free fuzzy logic controller (FLC) was adopted herein for our control scheme. Comparison between FLC and conventional proportional-derivative (PD) controllers demonstrated that the FLC with asymmetrical membership function enabled the subject with paraplegia to maintain varied desired cycling speeds, particularly at lower cycling speed. By incorporating the rational stimulation patterns, the FLC can produce a smooth and prolonged cycling movement deemed necessary for designing various training protocols.

A neuro-control system for the knee joint position control with quadriceps stimulation.

A neuro-control system was designed to control the knee joint to move in accordance with the desired trajectory of movement through stimulation of quadriceps muscle. This control system consisted of a neural controller and a fixed parameter proportional-integral-derivative (PID) feedback controller, which was designated as a neuro-PID controller. A multilayer feedforward time-delay neural network was used and trained as an inverse model of the functional electrical stimulation (FES)-induced quadriceps-lower leg system for direct feedforward control. The training signals for neural network learning were obtained from experimentation using a low-pass filtered random sequence to reveal the plant characteristics. The Nguyen-Widrow method was used to initialize the neural connection weights. The conjugate gradient descent algorithm was then used to modify these connection weights so as to minimize the errors between the desired outputs and the network outputs. The knee joint angle was controlled with only small deviations along the desired trajectory with the aid of the neural controller. In addition, the PID feedback controller was utilized to compensate for the residual tracking errors caused by disturbances and modeling errors. This control strategy was evaluated on one able-bodied and one paraplegic subject. The neuro-PID controller showed promise as a position controller of knee joint angle with quadriceps stimulation.

Real-time implementation of electromyogram pattern recognition as a control command of man-machine interface.

The purpose of this study was to develop a real-time electromyogram (EMG) discrimination system to provide control commands for man-machine interface applications. A host computer with a plug-in data acquisition and processing board containing a TMS320 C31 floating-point digital signal processor was used to attain real-time EMG classification. Two-channel EMG signals were collected by two pairs of surface electrodes located bilaterally between the sternocleidomastoid and the upper trapezius. Five motions of the neck and shoulders were discriminated for each subject. The zero-crossing rate was employed to detect the onset of muscle contraction. The cepstral coefficients, derived from autoregressive coefficients and estimated by a recursive least square algorithm, were used as the recognition features. These features were then discriminated using a modified maximum likelihood distance classifier. The total response time of this EMG discrimination system was achieved about within 0.17 s. Four able bodied and two C5/6 quadriplegic subjects took part in the experiment, and achieved 95% mean recognition rate in discrimination between the five specific motions. The response time and the reliability of recognition indicate that this system has the potential to discriminate body motions for man-machine interface applications.

Flutamide-associated liver toxicity during treatment with total androgen suppression and radiation therapy for prostate cancer.

PURPOSE: To examine the frequency and severity of toxicity associated with flutamide inpatients treated with total androgen suppression before and during pelvic radiation therapy (RT) for prostate cancer. MATERIALS AND METHODS: Sixty-five patients with T2b-T4 prostate cancer received flutamide and goserelin acetate for 4 months, with RT beginning at the 3rd month. Treatment records including liver function test (LFT) results at baseline and during treatment were reviewed and toxicities noted. RESULTS: In 30 (46%) of 65 patients, flutamide was discontinued prematurely. Primary reasons included elevation in LFT levels (n=14); gastro-intestinal toxicity (n=9); decreased hemoglobin level (n=2); patient refusal (n=2); and arthralgia, rash, and malaise (n=1 each). Hepatotoxicity generally was manifest as asymptomatic transaminase level elevation. Grade 3-4 hepatotoxicity was noted in four of 65 patients. Mean aspartase aminotransferase increased from 23 (baseline) to 67 U/L (during flutamide treatment) (P<.02); mean alanine aminotransferase level increased from 26 (baseline) to 94 U/L (during flutamide treatment) (P<.005). CONCLUSION: Flutamide toxicity was common. LFTs should be monitored during flutamide therapy. The role of flutamide in this treatment regimen may need to be reevaluated.

Testosterone secretion during early pregnancy in mares.

We have characterized the testosterone secretion pattern during the first 80 d of pregnancy in mares and determined the sources that contribute to circulating testosterone levels during this period. Ten untreated, pregnant mares (Group 1), 10 altrenogest-treated, pregnant mares (Group 2), and 10 altrenogest-treated, pregnant mares in which the CL was eliminated by administration of PGF-2alpha on Day 16 (Group 3) were used in this study. Complete luteolysis occurred following PGF-2alpha administration in all mares in Group 3. Six of the 10 mares in Group 3 did not have an active CL until after Day 60 of pregnancy (Group 3a) and were included in the analysis. The remaining four mares developed a new CL on Days 32, 40, 43 and 49 of pregnancy and were excluded from analysis. Mares without a functional CL (Group 3a) had significantly lower testosterone concentrations than mares with a functional CL (Groups 1 and 2), during the period before equine chorionic gonadotropin (eCG) secretion. At the onset of eCG secretion, testosterone concentrations increased rapidly but the rate of increase decreased with time in mares with a functional CL (Groups 1 and 2). In mares without a functional CL (Group 3a), testosterone concentrations did not increase at the onset of eCG secretion but increased at a gradually increasing rate after Day 50. The lower testosterone concentration in mares without a functional CL before eCG secretion suggests that the CL contributes significantly to the circulating testosterone concentration during the period before eCG secretion. The close time relationship between the onset of eCG secretion and the increase in testosterone secretion in mares with a functional CL and the lack of a testosterone increase in pregnant mares without a functional CL suggest that the increase in testosterone secretion after Day 35 of pregnancy is the result of eCG-stimulated, luteal testosterone synthesis.

Isolation and characterization of a novel human prostatic stromal cell culture: DuK50.

A novel human prostatic stromal cell culture, designated DuK50, has been passed in vitro > 12 mo. Tissue cultures were obtained from material harvested within a normal region of a radical prostatectomy specimen. These monolayers exhibited normal fibroblastic characteristics with each cell having a flattened, elongated appearance. Karyotypic analysis revealed a normal, male 46, XY chromosomal content with no numerical or structural abnormalities. DNA analysis using a Cell Analysis Systems Image Analyzer confirmed a euploid DNA content (7.9 pg DNA). Cellular markers for verification of stromal cell type were performed by immunohistochemical techniques. DuK50 stained positive for vimentin and fibronectin. Immunostains for epithelial cytokeratins and prostate-specific antigen were negative, which ruled out contamination with prostatic epithelial cells. Negative immunostaining with desmin monoclonal antibody and light staining with smooth muscle actin alpha is consistent with the staining pattern of myofibroblasts. Response to various androgens, measured by a microculture tetrazolium assay technique, revealed a significant growth stimulation of DuK50. Soft agar invasiveness assays and tumorigenicity studies in nude mice were negative. DuK50 exhibits a rapid doubling time with excellent plating efficiency, thrives in a readily available media supplemented with fetal bovine serum, and passes with routine trypsin protocols. The availability of this prostatic stromal cell culture may facilitate studies on this cell type's role in growth factor modulation, drug and steroid metabolism, and stromal-epithelial interactions in the prostate.

Genotypic analysis of Epstein-Barr virus isolates associated with nasopharyngeal carcinoma in Chinese immigrants to the United States.

EBV genotypes of first- and second-generation Chinese diagnosed with nasopharyngeal carcinoma in the United States were analyzed by PCR techniques. Previous studies showed a geographical distribution of genotypically distinct sub-types of EBV. Viruses detected at a higher frequency among Chinese NPC patients (Cf) were distinguished from those found in the majority of Caucasian NPC patients (DF) in the United States by polymorphisms in the BamHI F and I regions. Exploiting this distinction, we analyzed the biopsies of Chinese immigrants in the United States for their C/D and F/f genotypes to evaluate the importance of retention of the Cf virus among Chinese NPC patients in a geographical area where the DF virus prevails. This study shows that approximately 45.5 to 50% of first- and second-generation Chinese NPC patients in California harbor the Cf virus, which is present in only 8% of Caucasian NPC patients in California. It is interesting that, while only 48% of the viral isolates from immigrant Chinese to California harbor the "f" variant, 96% harbor the type-C viruses.

Excess cancer mortality among children and adolescents in residential districts polluted by petrochemical manufacturing plants in Taiwan.

We have collected data on the cancer deaths of children and adolescents 0-19 yr old living in a residential area near 3 large petroleum and petrochemical complexes in and near Kaohsiung city (petrochemical industrial districts, PIDs) in the period of 1971-1990 and compared these with the cancer deaths of children and adolescents 0-19 yr old among the entire population of Taiwan (national reference) and among the residents of 26 administrative districts, comprising all of Kaohsiung city and Kaohsiung county (local reference), except for 8 sparsely populated, rural districts. Having scrutinized all cancer death certificates, we have identified various statistically significant excess deaths, as compared with the national and local reference, due to cancers at all sites. Cancer of the bone, brain, and bladder in boys and girls 0-9 yr and 10-19 yr of age in the 1981-1990 decade that followed the establishment of petrochemical production in the PIDs was studied. However, excess cancer deaths seemed to have clustered in the 10-19 yr age group, who had been potentially exposed to the petrochemical pollutants for the longest period of time from the youngest age. Almost all bone, brain, and bladder cancer deaths registered were within 3 km of the 3 complexes. Bone and brain cancers in particular occurred in girls in the PIDs more frequently than in boys, even though these are believed to occur more in males than females elsewhere.

Rat fibroblasts transfected with the human 70-kDa heat shock gene exhibit altered translation and eukaryotic initiation factor 2 alpha phosphorylation following heat shock.

Heat shock inhibits translation in a wide variety of cells. After heating, eukaryotic initiation factor 2-alpha (eIF-2 alpha) becomes phosphorylated which prevents the binding of Met-tRNA to the 40s ribosomal subunit inhibiting initiation of translation. Thermotolerant cells demonstrate resistance to inhibition of translation by additional heating suggesting that heat shock proteins may help to maintain translational integrity following thermal stress. Here we have examined the effects of increased intracellular levels of hsp70 protein on translation and eIF-2 alpha phosphorylation using rat fibroblasts stably transfected with a cloned human hsp70 gene. We observed a decrease in the rate of translational inhibition following heat shock in both hsp70-transfected and thermotolerant cells. Upon recovery at 37 degrees C, both hsp70-transfected and thermotolerant cells exhibit a faster rate of translational recovery. Utilizing slab gel isoelectric focusing coupled with immunoblotting we demonstrate that 45 degrees C heat shock leads to a rapid 4-5-fold increase in eIF-2 alpha phosphorylation, with little difference seen between control cells and hsp70-transfected cells. However, dephosphorylation of eIF-2 alpha occurs faster in the hsp70-transfected cells. These results suggest that hsp70 may play a role in facilitating the dephosphorylation of eIF-2 alpha as well as reversing the inhibition of translation following heat shock.

Effect of gossypol on 5 alpha-reductase and 3 alpha-hydroxysteroid dehydrogenase activities in adult rat testes.

It has been reported that little to no 5 alpha-reductase can be detected in adult rat testes when progesterone is used as substrate. The 5 alpha-reductase activity in 4-month-old rats and the inhibitory action of gossypol on steroidobiosynthesis were studied. Testicular sections (10 microns thickness) were incubated at 30.5 degrees C in the presence of NADPH with 3H-testosterone and cold testosterone as substrates (9 microM total), and with or without gossypol as the test sample and control, respectively. Endogenous testosterone level was evaluated by radioimmunoassay. Reverse phase high performance liquid chromatography (HPLC) was used to separate the substrate and products. Components of interest were collected and their recovery monitored. At 200 microM concentration, gossypol significantly decreased dihydrotestosterone (DHT) formation by 21% when compared to that of control (0.6 pm/mg protein/min), and decreased 5 alpha-androstane-3 alpha,17 beta-diol formation by 35% vs control (2 pm/mg protein/min). In the current study, gossypol was found to have inhibitory effects of noncompetitive nature on 5 alpha-reductase, which catalyzes the conversion of testosterone to DHT, and on 3 alpha-hydroxysteroid dehydrogenase (3 alpha-HSD), which interconverts DHT and dihydroandrostanediol.

Biosynthesis and secretion of growth factor proteins by kidney cells from DES-treated Syrian hamsters.

Long-term estrogen treatment of Syrian hamsters results in the initiation and development of hormone-dependent renal adenocarcinomas. The pathway(s) to neoplastic transformation remain unknown in this animal model of hormonal carcinogenesis. In the present study, short-term primary kidney cell cultures and incubations of freshly prepared kidney slices have been incubated with [35S]-methionine to study the effects of estrogen treatment on protein biosynthesis in the Syrian hamster. An increase in amount of two secreted proteins were observed with an increasing duration of diethylstilbestrol (DES) treatment. Further characterization of these proteins by two-dimensional electrophoresis identified two proteins present only in treated hamsters, a 20-22 kDa protein and a 16-18 kDa protein with an isoelectric point of 8.5-9.0. Immunoprecipitation using specific antibodies to growth factors, followed by separation on SDS-PAGE electrophoresis, showed that kidney slices from five month-treated animals produced a TGF-alpha-like protein and a bFGF-like protein. The induction of these growth factors may play an important role in the tumorigenic process in kidneys of Syrian hamsters, including cell proliferation and vascularization of the tumor tissue.

Detection of distinct Epstein-Barr virus genotypes in NPC biopsies from southern Chinese and Caucasians.

Using the polymerase chain reaction (PCR) to analyze paraffin sections from 12 Caucasian patients, we detected only the prototype F Epstein-Barr virus (EBV) in 10 specimens from patients with nasopharyngeal carcinoma (NPC). This is in contrast to the higher frequency of association of "f" variants in NPC biopsies from Southern Chinese. The results of EBV genotyping support evidence that the EBV strains associated with NPC in the Southern Chinese population differ from those found in Caucasians. DNA sequencing confirmed that a simple point mutation is responsible for the restriction-fragment-length polymorphism which distinguishes the prototype F virus from the "f" variant.