Long-term outcomes of imiquimod-treated lentigo maligna.

BACKGROUND: Lentigo maligna (LM) may be disfiguring and can progress to LM melanoma. Surgical excision remains the mainstay of treatment, but may result in disfigurement when used for large facial lesions. Topical imiquimod is a nonsurgical alternative although data on its long-term efficacy remain limited. AIM: To assess long-term outcomes of LM treated with imiquimod cream. METHODS: We collected data retrospectively for 33 patients treated with imiquimod cream for biopsy-proven LM from 2001 to 2016. Patients initially applied imiquimod once daily, 5 days/week for 6 weeks, aiming to produce a brisk local inflammatory response. If there was no response, the dose was increased to twice daily 7 days/week for 6 weeks and if again there was no response, to twice daily for 10 weeks. RESULTS: An inflammatory response developed in 29 (88%) of the 33 patients, and of these, 4 patients stopped treatment earlier than planned because they could not tolerate the inflammatory reaction, while 3 patients reported systemic side effects. There was lesion clearance in 21 (72%) of the 29 patients, and they remained clear after a mean follow-up of 4.1 years. Eight failed to clear; in five the lesion was excised, while the remaining three were managed expectantly. CONCLUSIONS: Our results support the use of imiquimod as an alternative to surgery for the treatment of LM in selected cases. With adequate patient preparation, imiquimod is generally tolerated and can achieve excellent cosmetic results. A clinical response is more likely if there is a brisk inflammatory response, and LM will not resolve if there is no inflammatory response.

Prospective study of formalin-fixed Mohs surgery and haematoxylin and eosin stains with control contralateral biopsies for lentigo maligna: 5-year follow-up results.

BACKGROUND: There is little consensus on the optimum form of surgical management for lentigo maligna (LM). Currently, because malignant melanocytes spread down adnexal structures, full-thickness skin removal is the only surgical option. Interpretation of Mohs histological specimens is difficult because of the presence of abnormal melanocytes in otherwise normal sun-damaged skin. OBJECTIVES: To investigate Slow Mohs for surgical excision of LM, to see whether the use of control contralateral skin biopsies would enable the end point of excision to be more easily interpreted and to investigate factors that influence the subclinical amelanotic extensions of LM. METHODS: The Slow Mohs technique for formalin-fixed tissue was used in 74 patients with LM. Before surgery LMs were classified as well defined, poorly defined, incompletely excised or recurrent. Control biopsies were taken from healthy skin of the contralateral side. Specimens were processed in formalin, stained with haematoxylin and eosin (H&E) and the results read at 24-48 h. The excision margin required for complete excision was measured and patients were followed for a minimum of 5 years to exclude recurrence. RESULTS: On average the final excision margin required was 6·7 mm. Margins were significantly greater for ill-defined, recurrent and incompletely excised LM compared with well-defined LM. The presence of depigmented patches preoperatively did not correlate with the excision margin, but LMs showing nesting required significantly wider excision margins. There were seven (12%) recurrences at a mean 4·4 years after surgery in the group with 5-year follow-up. Recurrence occurred only in recurrent and ill-defined primary LM. CONCLUSIONS: The use of Slow Mohs formalin-fixed tissue and H&E section staining, even with comparator biopsies, does not provide sufficient discrimination to identify residual disease confidently.

Cancer-Causing Effects of Orthopaedic Metal Implants in Total Hip Arthroplasty.

BACKGROUND: Metal implants have been preferentially used in THA due to its biocompatibility, mechanical stability and durability. Yet concerns have emerged regarding their potential to release metallic ions, leading to long-term adverse effects, including carcinogenicity. This study aimed to investigate the risk of cancer development in patients with orthopaedic metal implants in total hip arthroplasty (THA). METHODS: Patients with THA conducted at a local tertiary implant centre from 2001-2008 were linked to the local cancer registry and followed up to the end of 2023. Standardized incidence ratios (SIRs) for cancer incidence and its confidence interval by Poisson distribution were calculated. Survival analysis was depicted using the Kaplan-Meier method, and the log-rank test was used to assess the differences across groups. RESULTS: The study cohort included 388 patients and 53 cancers diagnosed during follow-up, at least 5 years post THA. All-site cancer risks were increased in patients with THA (SIR: 1.97; 95% CI: 1.48-2.46), validated with chi-square analysis (chi-square = 15.2551, N = 100,388, p < 0.01). A statistically significant increase in multiple site-specific cancers including haematological cancers were identified. CONCLUSIONS: Patients with THA were found to have an increased risk for cancer compared to the general population during a mean follow-up of 16 years.

Comparison of the Cost-Effectiveness and Safety between Staged Bilateral Total Knee Arthroplasty and Simultaneous Bilateral Total Knee Arthroplasty: A Retrospective Cohort Study between 2001 and 2022.

A substantial proportion of Hong Kong's aging population suffers from osteoarthritis in both knees. Bilateral total knee arthroplasty (BTKA) is a surgical option for addressing this condition and can be performed via two approaches: simultaneous BTKA (SimBTKA) and staged BTKA (StaBTKA). We compared the cost-effectiveness and safety of these two methods in our institution. We retrospectively reviewed 2,372 patients (SimBTKA, 772; StaBTKA, 1,600; females, 1,780; males, 592; mean age at SimBTKA, 70.4 ± 7.99 years; mean age at StaBTKA, 66.4 ± 7.50 years; p < 0.001) who underwent BTKA in our institution from 2001 to 2022. Patients were categorized according to the surgical approach. Patients undergoing BTKA in our institution were included. Particularly for SimBTKA, patients were assessed by anesthetists to be medically fit before undergoing the procedure according to their age, American Society of Anesthesiologists status, and osteoarthritis severity. The primary outcome was the length of stay (LOS) after surgery. The secondary outcomes were the 30-day unintended readmission, intensive care unit (ICU) admission, and death. SimBTKA had a shorter mean total LOS (acute hospital + rehabilitation center; SimBTKA, 13.09 days; StaBTKA, 18.12 days; p < 0.001) and mean LOS in acute hospital (SimBTKA, 7.70 days; StaBTKA, 10.42 days; p < 0.001). However, no significant difference was found in the mean LOS in rehabilitation centers (SimBTKA, 5.47 days; StaBTKA, 6.32 days; p > 0.05) between the two approaches. The 30-day unintended readmission rate was lower in SimBTKA (SimBTKA, 2.07%; StaBTKA, 3.30%; odds ratio [OR] = 1.60; p > 0.05) but statistically insignificant. SimBTKA was less costly than StaBTKA by US$ 8,422.22 per patient. No significant differences in ICU admission and death rates were found (p > 0.05) between the two groups. SimBTKA had a shorter LOS and lower cost than StaBTKA and comparable complication rates. Therefore, SimBTKA should be indicated in medically stable patients.

Photoacoustic tomography as a method to estimate the optical fluence distribution in turbid media.

Currently, there are no non-invasive experimental methods available for measuring optical fluence distributions in tissue. We present photoacoustic tomography (PAT) as a method to approximate the relative optical fluence distribution in a homogeneous optically scattering medium. Three-dimensional photoacoustic images were captured with a near-full view PAT scanner in phantoms with known optical absorption and scatter properties. Resultant 3D PAT images were compared to the expected optical fluence distributions from Monte Carlo simulations and diffusion theory using volumetric and shape analysis. Volumetric analysis of PAT images compared well with the optical fluence distributions from simulation. Dice similarity coefficients ranged from 51 to 82%. The reduced scattering coefficient estimated from PAT images compared well to estimates from simulations for values below 0.5 mm-1. Near full-view PAT has been found to be useful for estimating the optical fluence distribution in an optically scattering medium. Further development is needed to extend the measurement range.

The IPASC data format: A consensus data format for photoacoustic imaging.

Photoacoustic imaging (PAI) is an emerging modality that has shown promise for improving patient management in a range of applications. Unfortunately, the current lack of uniformity in PAI data formats compromises inter-user data exchange and comparison, which impedes: technological progress; effective research collaboration; and efforts to deliver multi-centre clinical trials. To overcome this challenge, the International Photoacoustic Standardisation Consortium (IPASC) has established a data format with a defined consensus metadata structure and developed an open-source software application programming interface (API) to enable conversion from proprietary file formats into the IPASC format. The format is based on Hierarchical Data Format 5 (HDF5) and designed to store photoacoustic raw time series data. Internal quality control mechanisms are included to ensure completeness and consistency of the converted data. By unifying the variety of proprietary data and metadata definitions into a consensus format, IPASC hopes to facilitate the exchange and comparison of PAI data.

Satisfactory long-term survival, functional and radiological outcomes of open-wedge high tibial osteotomy for managing knee osteoarthritis: Minimum 10-year follow-up study.

BACKGROUND: This prospective cohort study was designed to evaluate the survivorship and functional outcomes associated with long-term results of medial open-wedge high tibial osteotomy (MOWHTO) for the treatment of medial compartment knee osteoarthritis in the Chinese population. Although MOWHTO is a well-established procedure in the management of medial osteoarthritis of the knee, the long-term outcome in the Chinese population has not been reported in current literature. We hypothesised that MOWHTO would result in long-term preservation of knee function in Chinese, similar to that reported in the Caucasian population. METHODS: A cohort of 22 young adult patients (age < 55 years old) undergoing MOWHTO for the treatment of symptomatic medial compartment knee osteoarthritis between 2002 and 2008 was retrospectively surveyed with a minimum follow-up of 10 years. Kaplan-Meier survival analysis was performed, and the failure modes were investigated. The outcomes on survival (not requiring arthroplasty), clinical outcome (Knee Society Knee Score and Knee Society Function Score) and range of motion (numeric rating scale) at preoperative, 1-year postoperative follow-up and at last follow-up (>10 years) were evaluated. In addition, the mechanical tibiofemoral angle was also measured. The Wilcoxon signed-rank test was used for statistical evaluation of nonparametric data in these related samples. RESULT: A total of 31 knees in these 22 cases were included. The follow-up rate was 100% at 13.4 ± 1.9 years (11-17). Mean age at time of surgery was 45.8 ± 9.5 years (18-53). At 10-year follow-up, four knees converted to require total knee arthroplasty (survival: 87.1%). Preoperative varus alignment with mechanical tibiofemoral angle of -9.26 ± 2.83 was corrected to 2.58 ± 2.46 after surgery and remained 2.01 ± 3.52 at the latest follow-up. Knee Society Knee Score increased significantly from 53.7 ± 11.1 preoperatively to 93.8 ± 6.8 at 1-year follow-up and 91.8 ± 9.7 at latest follow-up. Similarly, the functional score also increased significantly from 67.4 ± 21.0 preoperatively to 86.3 ± 14.5 at 1-year follow-up and 82.1 ± 16.6 at latest follow-up (p < 0.01). Whereas, the range of motion significantly decreased from 122.7 ± 6.6 preoperatively to 116.1 ± 15.5 at the latest follow-up. CONCLUSION: Even in cases of severe medial osteoarthritis and varus malalignment, MOWHTO would be a good treatment option for management in active Chinese population less than 55 years. Although the long-term survival and functional outcome after MOWHTO was proven to be satisfactory in our cohort during the 10-year follow-up, a larger cohort to illustrate the long-term functional outcome is still warranted. TRANSLATIONAL POTENTIAL: The finding in this study indicated MOWHTO is a feasible treatment option for young adult patients with osteoarthritis to achieve long-term satisfactory results.

Effect of tissue shrinkage on histological tumour-free margin after excision of basal cell carcinoma.

BACKGROUND: Histology reports of skin tumour excisions frequently describe a histological margin significantly less than the planned surgical excision margin. OBJECTIVES: A novel method of marking visible tumour margin was devised. This allowed us to evaluate the accuracy of tumour detection and to compare tissue contraction of the clinically normal perilesional skin with that of tumour tissue following excision and fixation. METHODS: Forty-four well-defined basal cell carcinomas were excised from 42 patients. The visible tumour edge was marked by scoring with a blade around its circumference prior to excision. This allowed comparison of visible and true histological tumour margin. The excision margin was carefully measured from the scored line and the tumour excised. After tissue fixation and processing the histological dimensions of tumour and perilesional margin skin were compared with the pre-excision measurements. RESULTS: The tumour edge was accurately identified to within 1 mm in 67% of margins and was underestimated in only 4%. The whole specimen contracted by a mean of 14%. Skin containing tumour contracted by a mean of 11% but adjacent tumour-free skin in the same plane contracted by a mean of 19%. There was no significant effect of age and site on difference in percentage shrinkage between tumour and margin. CONCLUSIONS: We underestimated tumour extent at only 4% of margins. Tissue shrinkage was the most important factor affecting eventual histological margin. Our novel technique allowed us to demonstrate that this shrinkage is not uniform across the specimen, but is disproportionately high in the tumour-free margin. This suggests that previous estimates of margin shrinkage, based on whole-specimen contraction measurements, may have been erroneously low.

Assessing Time-Resolved fNIRS for Brain-Computer Interface Applications of Mental Communication.

Brain-computer interfaces (BCIs) are becoming increasingly popular as a tool to improve the quality of life of patients with disabilities. Recently, time-resolved functional near-infrared spectroscopy (TR-fNIRS) based BCIs are gaining traction because of their enhanced depth sensitivity leading to lower signal contamination from the extracerebral layers. This study presents the first account of TR-fNIRS based BCI for "mental communication" on healthy participants. Twenty-one (21) participants were recruited and were repeatedly asked a series of questions where they were instructed to imagine playing tennis for "yes" and to stay relaxed for "no." The change in the mean time-of-flight of photons was used to calculate the change in concentrations of oxy- and deoxyhemoglobin since it provides a good compromise between depth sensitivity and signal-to-noise ratio. Features were extracted from the average oxyhemoglobin signals to classify them as "yes" or "no" responses. Linear-discriminant analysis (LDA) and support vector machine (SVM) classifiers were used to classify the responses using the leave-one-out cross-validation method. The overall accuracies achieved for all participants were 75% and 76%, using LDA and SVM, respectively. The results also reveal that there is no significant difference in accuracy between questions. In addition, physiological parameters [heart rate (HR) and mean arterial pressure (MAP)] were recorded on seven of the 21 participants during motor imagery (MI) and rest to investigate changes in these parameters between conditions. No significant difference in these parameters was found between conditions. These findings suggest that TR-fNIRS could be suitable as a BCI for patients with brain injuries.

Structured-light surface scanning system to evaluate breast morphology in standing and supine positions.

Breast shapes are affected by gravitational loads and deformities. Measurements obtained in the standing position may not correlate well with measurements in the supine position, which is more representative of patient position during breast surgery. A dual color 3D surface imaging system capable of scanning patients in both supine and standing positions was developed to evaluate the effect of changes in body posture on breast morphology. The system was evaluated with  breast phantoms to assess accuracy, then tested on ten subjects in three body postures to assess its effectiveness as a clinical tool. The accuracy of the system was within 0.4 mm on average across the model. For the human study, there was no effect of body posture on breast volumes (p value > 0.05), but we observed an effect of completeness of breast scans on body posture (p value < 0.05). Post-hoc tests showed that the supine position and the standing position with hands at the waist differed significantly (p value < 0.05). This study shows that the system can quantitatively evaluate the effect of subject postures, and thereby has the potential to be used to investigate peri-operative changes in breast morphology.

Perfusion and Metabolic Neuromonitoring during Ventricular Taps in Infants with Post-Hemorrhagic Ventricular Dilatation.

Post-hemorrhagic ventricular dilatation (PHVD) is characterized by a build-up of cerebral spinal fluid (CSF) in the ventricles, which increases intracranial pressure and compresses brain tissue. Clinical interventions (i.e., ventricular taps, VT) work to mitigate these complications through CSF drainage; however, the timing of these procedures remains imprecise. This study presents Neonatal NeuroMonitor (NNeMo), a portable optical device that combines broadband near-infrared spectroscopy (B-NIRS) and diffuse correlation spectroscopy (DCS) to provide simultaneous assessments of cerebral blood flow (CBF), tissue saturation (StO2), and the oxidation state of cytochrome c oxidase (oxCCO). In this study, NNeMo was used to monitor cerebral hemodynamics and metabolism in PHVD patients selected for a VT. Across multiple VTs in four patients, no significant changes were found in any of the three parameters: CBF increased by 14.6 ± 37.6% (p = 0.09), StO2 by 1.9 ± 4.9% (p = 0.2), and oxCCO by 0.4 ± 0.6 µM (p = 0.09). However, removing outliers resulted in significant, but small, increases in CBF (6.0 ± 7.7%) and oxCCO (0.1 ± 0.1 µM). The results of this study demonstrate NNeMo's ability to provide safe, non-invasive measurements of cerebral perfusion and metabolism for neuromonitoring applications in the neonatal intensive care unit.

Optical monitoring of cerebral perfusion and metabolism in adults during cardiac surgery with cardiopulmonary bypass.

During cardiac surgery with cardiopulmonary bypass (CPB), adequate maintenance of cerebral blood flow (CBF) is vital in preventing postoperative neurological injury - i.e. stroke, delirium, cognitive impairment. Reductions in CBF large enough to impact cerebral energy metabolism can lead to tissue damage and subsequent brain injury. Current methods for neuromonitoring during surgery are limited. This study presents the clinical translation of a hybrid optical neuromonitor for continuous intraoperative monitoring of cerebral perfusion and metabolism in ten patients undergoing non-emergent cardiac surgery with non-pulsatile CPB. The optical system combines broadband near-infrared spectroscopy (B-NIRS) to measure changes in the oxidation state of cytochrome c oxidase (oxCCO) - a direct marker of cellular energy metabolism - and diffuse correlation spectroscopy (DCS) to provide an index of cerebral blood flow (CBFi). As the heart was arrested and the CPB-pump started, increases in CBFi (88.5 ± 125.7%) and significant decreases in oxCCO (-0.5 ± 0.2 µM) were observed; no changes were noted during transitions off CPB. Fifteen hypoperfusion events, defined as large and sustained reductions in CPB-pump flow rate, were identified across all patients and resulted in significant decreases in perfusion and metabolism when mean arterial pressure dropped to 30 mmHg or below. The maximum reduction in cerebral blood flow preceded the corresponding metabolic reduction by 18.2 ± 15.0 s. Optical neuromonitoring provides a safe and non-invasive approach for assessing intraoperative perfusion and metabolism and has potential in guiding patient management to prevent adverse clinical outcomes.

Avian influenza virus A/HK/483/97(H5N1) NS1 protein induces apoptosis in human airway epithelial cells.

Avian H5N1 influenza virus causes a remarkably severe disease in humans, with an overall case fatality rate of greater than 50%. Human influenza A viruses induce apoptosis in infected cells, which can lead to organ dysfunction. To verify the role of H5N1-encoded NS1 in inducing apoptosis, the NS1 gene was cloned and expressed in human airway epithelial cells (NCI-H292 cells). The apoptotic events posttransfection were examined by a terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick-end-labeling assay, flow cytometric measurement of propidium iodide, annexin V staining, and Western blot analyses with antibodies specific for proapoptotic and antiapoptotic proteins. We demonstrated that the expression of H5N1 NS1 protein in NCI-H292 cells was sufficient to induce apoptotic cell death. Western blot analyses also showed that there was prominent cleavage of poly(ADP-ribose) polymerase and activation of caspase-3, caspase-7, and caspase-8 during the NS1-induced apoptosis. The results of caspase inhibitor assays further confirmed the involvement of caspase-dependent pathways in the NS1-induced apoptosis. Interestingly, the ability of H5N1 NS1 protein to induce apoptosis was much enhanced in cells pretreated with Fas ligand (the time posttransfection required to reach >30% apoptosis was reduced from 24 to 6 h). Furthermore, 24 h posttransfection, an increase in Fas ligand mRNA expression of about 5.6-fold was detected in cells transfected with H5N1 NS1. In conclusion, we demonstrated that the NS1 protein encoded by avian influenza A virus H5N1 induced apoptosis in human lung epithelial cells, mainly via the caspase-dependent pathway, which encourages further investigation into the potential for the NS1 protein to be a novel therapeutic target.

Formalin-fixed tissue Mohs surgery (slow Mohs) for basal cell carcinoma: 5-year follow-up data.

BACKGROUND: Mohs surgery using a formalin-fixed tissue technique (slow Mohs) was used to treat 1090 basal cell carcinomas (BCCs) occurring in 1000 patients without Gorlin syndrome in a prospective, open nonrandomized trial of therapy carried out in a university dermatology department. OBJECTIVES: To record outcomes and 5-year cure rates in these patients. RESULTS: Five multirecurrent BCCs could not be cleared and Mohs surgery was abandoned. In the remaining 1085 BCCs, after debulking, clearance was achieved with a mean of 1.7 stages and 7.7 blocks. Logistic regression analysis showed that large tumour size and position on the nose were the only factors that significantly predicted the risk of tumour excision requiring more than two Mohs stages. Wounds were managed by the Mohs surgeon (n = 917), by an oculoplastic surgeon (n = 117) and by a plastic or other surgeon (n = 56). The mean interval between the first Mohs excision and Mohs clearance, regardless of the closure technique, was 4.2 days (range 0-44) and the mean interval between tumour clearance and defect closure was 1.9 days (range 0-49). Reconstruction of 117 periocular defects by the oculoplastic surgeon was done at a mean of 0.8 days (range 0-6) after Mohs clearance. Reconstruction by the plastic surgeon was done at a mean of 10 days (range 0-49) after Mohs clearance. Five-year follow up was possible in 750 BCCs. Within this group 21 tumour recurrences were identified, giving a 5-year cure rate of 97.2% for all patients, 97.8% for primary BCC and 95.3% for recurrent BCC. The mean tumour recurrence time was 2.5 years (range 0.6-4.99) following Mohs excision. There was a higher risk of recurrence for big (four of 78; 5%) and recurrent (nine of 193; 5%) BCCs compared with other indications for Mohs surgery. CONCLUSIONS: The essential difference between frozen sections and formalin-fixed sections is the greater use of an automated laboratory system to process the smaller size and greater number of blocks produced using the latter process. An effective Mohs service based on formalin-fixed sections requires a minimum of three half-day operating sessions together with a pathology laboratory able to provide results routinely within 24-48 h. A formalin-fixed tissue Mohs service is useful for certain skin tumours and requires less technician time than a frozen section service but this advantage may not outweigh the inconvenience to the patient.

Crystal structure of Pseudomonas mevalonii HMG-CoA reductase at 3.0 angstrom resolution.

The rate-limiting step in cholesterol biosynthesis in mammals is catalyzed by 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a four-electron oxidoreductase that converts HMG-CoA to mevalonate. The crystal structure of HMG-CoA reductase from Pseudomonas mevalonii was determined at 3.0 angstrom resolution by multiple isomorphous replacement. The structure reveals a tightly bound dimer that brings together at the subunit interface the conserved residues implicated in substrate binding and catalysis. These dimers are packed about a threefold crystallographic axis, forming a hexamer with 23 point group symmetry. Difference Fourier studies reveal the binding sites for the substrates HMG-CoA and reduced or oxidized nicotinamide adenine dinucleotide [NAD(H)] and demonstrate that the active sites are at the dimer interfaces. The HMG-CoA is bound by a domain with an unusual fold, consisting of a central alpha helix surrounded by a triangular set of walls of beta sheets and alpha helices. The NAD(H) is bound by a domain characterized by an antiparallel beta structure that defines a class of dinucleotide-binding domains.

Crystal structure of the ectodomain of human transferrin receptor.

The transferrin receptor (TfR) undergoes multiple rounds of clathrin-mediated endocytosis and reemergence at the cell surface, importing iron-loaded transferrin (Tf) and recycling apotransferrin after discharge of iron in the endosome. The crystal structure of the dimeric ectodomain of the human TfR, determined here to 3.2 angstroms resolution, reveals a three-domain subunit. One domain closely resembles carboxy- and aminopeptidases, and features of membrane glutamate carboxypeptidase can be deduced from the TfR structure. A model is proposed for Tf binding to the receptor.

Chemical composition and antiproliferative activity of essential oil from the leaves of a medicinal herb, Schefflera heptaphylla.

Schefflera heptaphylla (L.) Frodin is a medicinal herb widely used as a main ingredient of the popular health tea formulation against infections in Southern China. Twenty-seven volatile compounds were identified by GC-MS analysis from the essential oil obtained from the leaves of S. heptaphylla, and 17 of them belonged to monoterpenes or sesquiterpenes. The main volatile constituent in S. heptaphylla was found to be a monoterpene, beta-pinene, comprising about 22% of the total volatile components. The essential oil showed significant antiproliferative activity against three cancer cell lines, MCF-7, A375 and HepG2 cells, with IC50 values of 7.3 microg/mL, 7.5 microg/mL and 6.9 microg/mL, respectively. The result of the cytotoxicity assay indicates that (-)-beta-pinene and (+)-beta-pinene (commercially available from Sigma) also possessed antiproliferative activity against the cancer cells MCF-7, A375 and HepG2 with IC50 values ranging from 147.1 to 264.7 microm.