Paediatric Anatomical Models in Radiotherapy Applications.

Anatomical models have key applications in radiotherapy, notably to help understand the relationship between radiation dose and risk of developing side effects. This review analyses whether age-specific computational phantoms, developed from healthy subjects and paediatric cancer patient data, are adequate to model a paediatric population. The phantoms used in the study were International Commission on Radiological Protection (ICRP), 4D extended cardiac torso (XCAT) and Radiotherapy Paediatric Atlas (RT-PAL), which were also compared to literature data. Organ volume data for 19 organs was collected for all phantoms and literature. ICRP was treated as the reference for comparison, and percentage difference (P.D) for the other phantoms were calculated relative to ICRP. Overall comparisons were made for each age category (1, 5, 10, 15) and each organ. Statistical analysis was performed using Microsoft Excel (version 16.59). The smallest P.D to ICRP was for Literature (-17.4%), closely followed by XCAT (26.6%). The largest was for RT-PAL (88.1%). The rectum had the largest average P.D (1,049.2%) and the large bowel had the smallest (2.0%). The P.D was 122.6% at age 1 but this decreased to 43.5% by age 15. Linear regression analysis showed a correlation between organ volume and age to be the strongest for ICRP (R2 = 0.943) and weakest for XCAT (R2 = 0.676). The phantoms are similar enough to ICRP for potential use in modelling paediatric populations. ICRP and XCAT could be used to model a healthy population, whereas RT-PAL could be used for a population undergoing/after radiotherapy.

A phase II open-label trial of avelumab plus axitinib in previously treated non-small-cell lung cancer or treatment-naïve, cisplatin-ineligible urothelial cancer.

BACKGROUND: We hypothesized that avelumab plus axitinib could improve clinical outcomes in patients with advanced non-small-cell lung cancer (NSCLC) or urothelial carcinoma (UC). PATIENTS AND METHODS: We enrolled previously treated patients with advanced or metastatic NSCLC, or untreated, cisplatin-ineligible patients with advanced or metastatic UC. Patients received avelumab 800 mg every 2 weeks (Q2W) and axitinib 5 mg orally two times daily. The primary endpoint was objective response rate (ORR). Immunohistochemistry was used to assess programmed death-ligand 1 (PD-L1) expression (SP263 assay) and the presence of CD8+ T cells (clone C8/144B). Tumor mutational burden (TMB) was assessed by whole-exome sequencing. RESULTS: A total of 61 patients were enrolled and treated (NSCLC, n = 41; UC, n = 20); 5 remained on treatment at data cut-off (26 February 2021). The confirmed ORR was 31.7% in the NSCLC cohort and 10.0% in the UC cohort (all partial responses). Antitumor activity was observed irrespective of PD-L1 expression. In exploratory subgroups, ORRs were higher in patients with higher (≥median) CD8+ T cells in the tumor. ORRs were higher in patients with lower TMB (

Plastic waste recycling: existing Indian scenario and future opportunities.

This review article aims to suggest recycling technological options in India and illustrates plastic recycling clusters and reprocessing infrastructure for plastic waste (PW) recycling in India. The study shows that a majority of states in India are engaged in recycling, road construction, and co-processing in cement kilns while reprocessing capabilities among the reprocessors are highest for polypropylene (PP) and polyethylene (PE) polymer materials. This review suggests that there are key opportunities for mechanical recycling, chemical recycling, waste-to-energy approaches, and bio-based polymers as an alternative to deliver impact to India's PW problem. On the other hand, overall, polyurethane, nylon, and polyethylene terephthalate appear most competitive for chemical recycling. Compared to conventional fossil fuel energy sources, polyethylene (PE), polypropylene (PP), and polystyrene are the three main polymers with higher calorific values suitable for energy production. Also, multi-sensor-based artificial intelligence and blockchain technology and digitization for PW recycling can prove to be the future for India in the waste flow chain and its management. Overall, for a circular plastic economy in India, there is a necessity for a technology-enabled accountable quality-assured collaborative supply chain of virgin and recycled material. Supplementary Information: The online version contains supplementary material available at 10.1007/s13762-022-04079-x.

Rates of cannabis use in patients with cancer.

Background: A comprehensive assessment of cannabis use by patients with cancer has not previously been reported. In this study, we aimed to characterize patient perspectives about cannabis and its use. Methods: An anonymous survey about cannabis use was offered to patients 18 years of age and older attending 2 comprehensive and 2 community cancer centres, comprising an entire provincial health care jurisdiction in Canada (ethics id: hreba-17011). Results: Of 3138 surveys distributed, 2040 surveys were returned (65%), with 1987 being sufficiently complete for analysis (response rate: 63%). Of the respondents, 812 (41%) were less than 60 years of age; 45% identified as male, and 55% as female; and 44% had completed college or higher education.Of respondents overall, 43% reported any lifetime cannabis use. That finding was independent of age, sex, education level, and cancer histology. Cannabis was acquired through friends (80%), regulated medical dispensaries (10%), and other means (6%). Of patients with any use, 81% had used dried leaves.Of the 356 patients who reported cannabis use within the 6 months preceding the survey (18% of respondents with sufficiently complete surveys), 36% were new users. Their reasons for use included cancer-related pain (46%), nausea (34%), other cancer symptoms (31%), and non-cancer-related reasons (56%). Conclusions: The survey demonstrated that prior cannabis use was widespread among patients with cancer (43%). One in eight respondents identified at least 1 cancer-related symptom for which they were using cannabis.

Bites by the Monocled Cobra, Naja kaouthia, in Chittagong Division, Bangladesh: Epidemiology, Clinical Features of Envenoming and Management of 70 Identified Cases.

AbstractWe describe 70 cases of monocled cobra (Naja kaouthia) bite admitted to Chittagong Medical College Hospital, Bangladesh. The biting snakes were identified by examining the dead snake and/or detecting N. kaouthia venom antigens in patients' serum. Bites were most common in the early morning and evening during the monsoon (May-July). Ligatures were routinely applied to the bitten limb before admission. Thirty-seven patients consulted traditional healers, most of whom made incisions around the bite site. Fifty-eight patients experienced severe neurotoxicity and most suffered swelling and pain of the bitten limb. The use of an Indian polyvalent antivenom in patients exhibiting severe neurotoxicity resulted in clinical improvement but most patients experienced moderate-to-severe adverse reactions. Antivenom did not influence local blistering and necrosis appearing in 19 patients; 12 required debridement. Edrophonium significantly improved the ability of patients to open the eyes, endurance of upward gaze, and peak expiratory flow rate suggesting that a longer-acting anticholinesterase drug (neostigmine) could be recommended for first aid. The study suggested that regionally appropriate antivenom should be raised against the venoms of the major envenoming species of Bangladesh and highlighted the need to improve the training of staff of local medical centers and to invest in the basic health infrastructure in rural communities.

Role of folic Acid on symptoms of chronic arsenic toxicity.

BACKGROUND: Chronic arsenic toxicity (Arsenicosis) due to drinking of arsenic contaminated ground water is a global problem. However, its treatment is unsatisfactory. Methylation of arsenic facilitates its urinary excretion. Persons with relatively lower proportion of urinary dimethyl arsenic acid (DMA) are found to have at greater risk of developing symptoms of arsenicosis including its complications. The biochemical pathway responsible for methylation of arsenic is a folate-dependent pathway. Studies in rodents and humans suggest that folate nutritional status influences the metabolism of arsenic. METHODS: The present study compares the effect of giving folic acid on 32 arsenicosis patients during a 6-month period and comparing the results with clinical effect of taking only arsenic-free safe water on 45 age and sex-matched arsenic-affected people for the same period. RESULTS: There was significant improvement of arsenical skin lesion score of both patients treated with folic acid (2.96 ± 1.46 to 1.90 ± 0.90, P < 0.001) and arsenic free safe water (2.91 ± 1.26 to 1.62 ± 1.05, P < 0.001) for a period of 6 months. Significant improvement in systemic disease score was also observed from the baseline systemic score in folic acid treated group (4.78 ± 3.43 to 1.00 ± 1.56, P < 0.001) and the group treated with arsenic-free water (1.87 ± 2.11 to 0.82 ± 1.62, P < 0.001). However, there was a significant increased improvement of systematic disease score in the folic acid treated group compared to the control group taking arsenic free water (P < 0.001). CONCLUSIONS: This study provides evidence that folic acid treatment in arsenicosis cases could help in reducing clinical symptoms of arsenicosis.

Phase II study of magnesium sulfate in acute organophosphate pesticide poisoning.

BACKGROUND: Acute organophosphorus (OP) poisoning is relatively common and a major cause of death from poisoning in developing countries. Magnesium has been shown to be of benefit in animal models. METHODS: We conducted a phase II study of bolus doses of (MgSO4) in 50 patients with acute organophosphate poisoning. Patients eligible for inclusion had ingested OP and had cholinergic symptoms consistent with moderate or severe poisoning. All patients received standard care of atropinization titrated to control muscarinic symptoms and pralidoxime. The trial was run in 4 sequential groups of patients. Participants in each group received a different total dose of MgSO4 (20%) administered as intermittent bolus doses infused over 10-15 min or placebo. There was one control patient for every 4 patients who received MgSO4. Group A (16 patients) received a total of 4 gm MgSO4 as a single bolus, group B (8 patients) received 8 gm (in two 4 gm doses q4H), group C (8 patients) received 12 gm (in three 4 gm doses q4H) group D (8 patients) received 16 gm (in four 4 gm doses q4H) and control (10 patients) received placebo). Patients were closely monitored for any adverse reaction like significant clinical neuromuscular disturbance and respiratory depression. RESULTS: No adverse reactions to magnesium were observed. The 24 hour urinary magnesium concentration were statistically different between 16 gm (234.74 ± 74.18 mg/dl) and control (118.06 ± 30.76 mg/dl) (p = 0.019), while it was much lower than the 80% of the intravenous magnesium load. Six patients died in control group compared to 3 in 4 gm, 2 in 8 gm and 1 in 12 gm group. There was no mortality in 16 gm group. CONCLUSION: Magnesium was well tolerated in this study. Larger studies are required to examine for efficacy.

Treatment for glioblastoma multiforme: current guidelines and Canadian practice.

PURPOSE: Our survey aimed to document variability in the practice patterns of Canadian radiation oncologists treating high-grade brain tumours. MATERIALS AND METHODS: A 20-question survey was developed to address various aspects of treatment: Guidelines usedTypes of fusion protocols usedNumber of treatment phasesMargins for volume delineationDose constraintsThe survey was sent to Canadian radiation oncologists currently treating the central nervous system (cns) as one of their primary sites. RESULTS: We attained a 56% response rate from radiation oncologists across Canada treating cns sites. In their practice, 14% of respondents reported following guidelines from the European Organisation for Research and Treatment of Cancer; 32%, from the Radiation Therapy Oncology Group; and 56%, centre-specific guidelines. Single-phase treatment was reported by 60% of clinicians, and two-phase or multi-phase treatments, by 37%. For clinicians treating in single phase, margins from the gross treatment volume (gtv) to the planning treatment volume (ptv) included 0.5 cm (6%), 1 cm (6%), 1.5 cm (25%), 2.0 cm (56%), 2.5 cm (25%), and 3 cm (12.5%), with some respondents selecting more than one standard margin. For clinicians treating in multiple phases, margins from gtv to ptv in phase 2 included 1 cm (10%), 2.0 cm (40%), 2.5 cm (30%), and 3.0 cm (20%). Variability was also observed in dose constraints to critical structures. All respondents trimmed their margins to bony structures. CONCLUSIONS: Our survey shows considerable variation in the current treatment by Canadian radiation oncologists of high-grade brain tumours, especially with respect to guidelines followed, number of phases, and overall volume treated. Further studies are thus required to establish the evidence for optimal radiation volumes and phases, especially as brain tumour treatments evolve in the age of mr imaging and chemotherapy.

Clinical and laboratory parameters of pleural tuberculosis.

This prospective observational clinical study was done to find out the clinical and laboratory parameters of pleural tuberculosis patients, to find out a sensitive and specific tool for diagnosis and to see the effectively of a standard anti-TB regime Isoniazide, Rifampicine, Pyrazinamide, Ethambutol, (2HRZE/4HR) for treatment of pleural tuberculosis in an adult medicine unit, department of Medicine, Chittagong Medical College Hospital, Chittagong, Bangladesh. A series of total thirty-three consecutive pleural tuberculosis patients admitted in that unit over a period of 6 months were enrolled. All thirty-three pleural tuberculosis patients were observed for their demographic and clinical parameters and undergone some relevant investigations like complete blood count, Mantoux test, pleural fluid study and pleural histopathological study. Later on, they were put on anti-tuberculosis therapy without steroid and followed their response after one month. All patients of pleural tuberculosis presented in this medicine unit had fever and cough associated with chest pain (87.9%), dysnoea (42.4%), haemoptysis (9.1%), weight loss (84.4%), anorexia (90.9%). Age of presentation was 34.1+/-16.2 years and of them, 60.7% patients were below 30. Mean Erythrocyte Sedimentation Rate (ESR) was 97.04 mm in 1st hour and 57.6% cases had ESR more than 100. 63.6% had Mantoux Test (MT) positive (>10 mm). Only 6.1% had hemorrhagic effusion and others had straw colored fluid. Mean pleural fluid protein is 5.9 gram/L and sugar 65.7 mg/dl. No Acid Fast Bacilli (AFB) was seen on microscopy in pleural fluid. Pleural biopsy revealed 54.5% granulomatous lesion with or without caseation and another 24.2% shows chronic inflammation. Seventy seven percentage (77%) patients were attended follow-up clinic after 1 month and all patients (100%) were improved with this anti-TB therapy. Of the total patient treated with anti TB drug, 53.5% had no pleural effusion, other had minimum effusion. Only 6.06% require subsequent steroid addition and other measures. Pleural biopsy is the investigations of choice for pleural tuberculosis especially in resource poor countries. Pleural tuberculosis can be treated with a standard anti-TB regime successfully without steroid.

Clinical efficacy of Shatapushpa (Anethum sowa Kurz.) powder in the management of Artava kshaya (oligomenorrhoea).

A clinical trial was carried out on 30 oligomenorrhoea [Artava Kshaya] patients aged between 15 and 35 years having complaints of irregular, scanty and painful menstruations. The patients were registered from OPD and IPD of Gopabandhu Ayurveda Mahavidyalaya Puri. They were administrated Satapuspa churna for three months in a dose of 5 g twice daily with cow grita. The specific investigations were done in order to exclude TB endometritis, endocrine disorders, diabetes and heart disease. The clinical assessment was carried out in thirty days intervals. It is inferred that the study discloses the effect of satapuspa churna on irregularity of interval of menstruation [90.47%], duration of menstruation [79.37%], amount of blood flow [90.00%] and pain during menstruation [100.00%] which were highly significant in clinical study. No untoward side effect was noticed during clinical trial.

Systemic manifestations in chronic arsenic toxicity in absence of skin lesions in West Bengal.

BACKGROUND & OBJECTIVE: Pigmentation and keratosis are the prerequisites to diagnose arsenicosis. However, many systemic manifestations occur in association with pigmentation and keratosis in people exposed to chronic drinking of arsenic contaminated water. The present study aim to find out whether systemic manifestations occur in significant number of cases in arsenic exposed people in the absence of skin lesions in an affected district in West Bengal, India. METHODS: A cross-sectional study was carried out in South 24 Parganas, an arsenic affected district of West Bengal, India. Both dermatological and systemic manifestations were recorded and water samples collected for arsenic analysis from 7683 participants. A correlation of systemic manifestations in relation to arsenic exposure was carried out in subjects having no arsenical skin lesion. Prevalence odds ratio (POR) was calculated for each outcome comparing those with high arsenic exposure with those with lowest exposure. RESULTS: The frequency of occurrence of various clinical manifestations like weakness, anaemia, diarrhoea, hepatomegaly and lung disease was found to be significantly higher among participants drinking water having arsenic concentration > or = 50 microg/l in comparison to those taking water with arsenic content below this level. Further, there was increased occurrence of these manifestations with increasing concentration of arsenic level in drinking water, and this followed a dose-response relationship. INTERPRETATION & CONCLUSION: It appears that it is worthwhile to include people with systemic manifestations in absence of skin lesions with evidence of arsenic exposure as suspected cases of arsenicosis for case detection and in surveillance programme.

Direct in vivo assessment of microcirculatory dysfunction in severe falciparum malaria.

BACKGROUND: This study sought to describe and quantify microcirculatory changes in the mucosal surfaces of patients with severe malaria, by direct in vivo observation using orthogonal polarization spectral (OPS) imaging. METHODS: The microcirculation in the rectal mucosa of adult patients with severe malaria was assessed by use of OPS imaging, at admission and then daily. Comparison groups comprised patients with uncomplicated falciparum malaria, patients with bacterial sepsis, and healthy individuals. RESULTS: Erythrocyte velocities were measured directly in 43 adult patients with severe falciparum malaria, of whom 20 died. Microcirculatory blood flow was markedly disturbed, with heterogeneous obstruction that was proportional to severity of disease. Blocked capillaries were found in 29 patients (67%) and were associated with concurrent hyperdynamic blood flow (erythrocyte velocity, >750 mm/s) in adjacent vessels in 27 patients (93%). The proportion of blocked capillaries correlated with the base deficit in plasma and with the concentration of lactate. Abnormalities disappeared when the patients recovered. In healthy individuals and in patients with uncomplicated malaria or sepsis, no stagnant erythrocytes were detected, and, in patients with sepsis, hyperdynamic blood flow was prominent. CONCLUSION: Patients with severe falciparum malaria show extensive microvascular obstruction that is proportional to the severity of the disease. This finding underscores the prominent role that microvascular obstruction plays in the pathophysiology of severe malaria and illustrates the fundamental difference between the microvascular pathophysiology of malaria and that of bacterial sepsis.

Consecutive bites on two persons by the same cobra: a case report

In tropical countries like Bangladesh, persons are bitten by snakes every day and a considerable number of patients die en route to the hospital. An event of consecutive neurotoxic bites on two men by a single snake was observed in the Snake Bite Study Clinic (SBSC) of the Chittagong Medical College Hospital (CMCH). Two brothers, working in their semi-pucca restaurant, were successively bitten by the same cobra on their lower limbs. Within an hour, they were taken to the CMCH. Few minutes after admission, both developed symptoms of neurotoxicity: ptosis, nasal voice, dysphagia, broken neck sign, etc. They received polyvalent antivenom (Haffkine Bio-Pharmaceuticals Company, India) and other auxiliary treatment immediately. Within few hours, neurotoxic features were completely absent. Later, the snake was captured in the restaurant kitchen and identified as monocellate cobra (Naja kauthia) by the SBSC. The elder brother developed significant antivenom reactions and both presented necrosis and ulceration at the bite sites. In these cases, immediate arrival to the hospital and early administration of antivenom resulted in successful recoveries.

Consecutive bites on two persons by the same cobra: a case report

In tropical countries like Bangladesh, persons are bitten by snakes every day and a considerable number of patients die en route to the hospital. An event of consecutive neurotoxic bites on two men by a single snake was observed in the Snake Bite Study Clinic (SBSC) of the Chittagong Medical College Hospital (CMCH). Two brothers, working in their semi-pucca restaurant, were successively bitten by the same cobra on their lower limbs. Within an hour, they were taken to the CMCH. Few minutes after admission, both developed symptoms of neurotoxicity: ptosis, nasal voice, dysphagia, broken neck sign, etc. They received polyvalent antivenom (Haffkine Bio-Pharmaceuticals Company, India) and other auxiliary treatment immediately. Within few hours, neurotoxic features were completely absent. Later, the snake was captured in the restaurant kitchen and identified as monocellate cobra (Naja kauthia) by the SBSC. The elder brother developed significant antivenom reactions and both presented necrosis and ulceration at the bite sites. In these cases, immediate arrival to the hospital and early administration of antivenom resulted in successful recoveries.(AU)

Anti-snake venom: use and adverse reaction in a snake bite study clinic in Bangladesh

Snakebites can present local or systemic envenomation, while neurotoxicity and respiratory paralysis are the main cause of death. The mainstay of management is anti-snake venom (ASV), which is highly effective, but liable to cause severe adverse reactions including anaphylaxis. The types of adverse reaction to polyvalent anti-snake venom have not been previously studied in Bangladesh. In this prospective observational study carried out between 1999 and 2001, in the Snake Bite Study Clinic of Chittagong Medical College Hospital, 35 neurotoxic-snake-bite patients who had received polyvalent anti-snake venom were included while the ones sensitized to different antitoxins and suffering from atopy were excluded. The common neurotoxic features were ptosis (100%), external ophthalmoplegia (94.2%), dysphagia (77.1%), dysphonia (68.5%) and broken neck sign (80%). The percentage of anti-snake venom reaction cases was 88.57%; pyrogenic reaction was 80.64%; and anaphylaxis was 64.51%. The common features of anaphylaxis were urticaria (80%); vomiting and wheezing (40%); and angioedema (10%). The anti-snake venom reaction was treated mainly with adrenaline for anaphylaxis and paracetamol suppository in pyrogenic reactions. The average recovery time was 4.5 hours. Due to the danger of reactions the anti-snake venom should not be withheld from a snakebite victim when indicated and appropriate guidelines should be followed for its administration.(AU)

Use of the measure of process of care for families (MPOC-56) and service providers (MPOC-SP) to evaluate family-centred services in a paediatric disability setting.

BACKGROUND: The value of family-centred principles in paediatric professional caregiving services is widely acknowledged. However, the degree to which such services adhere to these principles is not well documented. AIM: To examine the perceptions of both families and service providers of the extent to which family-centred services were being implemented by a paediatric disability service provider and to pinpoint areas for improvement. METHOD: A sample of 158 families receiving services from the Cerebral Palsy Association of Western Australia completed the Measure of Processes of Care for families (MPOC-56) and 43 clinicians (most of them physiotherapists, speech pathologists and occupational therapists) completed the Measure of Processes of Care for service providers (MPOC-SP). RESULTS: As in previous studies, the families rated 'respectful and supportive care' highest and 'providing general information' lowest. Clinicians rated 'showing interpersonal sensitivity' highest and 'providing general information' lowest. Analysis of individual items revealed that the following areas of family-centred services were in need of improvement: provision of general written information to families on a range of issues, continuity of care, greater involvement of the family in therapy and provision of more detailed information about therapy issues and provision of more general support to whole families. CONCLUSIONS: The MPOC tools have been found useful in enabling disability service providers to identify areas for improvement and move towards providing services that are more family centred.

Efficacy of the phosphorylation of synthetic peptides by purified catalytic subunit of PKA (PKAcat) from bovine lens depends on the amino acid sequence of the peptides.

Protein kinase (PK) A catalytic (PKAcat) subunit was purified to homogeneity from bovine lens using a 100-kDa cut-off membrane filtration followed by different chromatographic procedures. The molecular weight of PKAcat was found to be 41 kDa. The kinase phosphorylates histone IIIs and other synthetic modified peptides of VRKRTLRRL with different amino acid environment. The extent of phosphorylation depends not only on the presence of Ser or Thr (phosphorylating residues) but also on other surrounding amino acid residues. Although some peptides compete in phosphorylating histone, they are not very significant. The result suggests that the extent of phosphorylation depends on the amino acid residue(s) surrounding phosphorylable residue(s) on the peptide.

ALVAC-mediated gene transfer is efficient in lymphoid malignancies of T-and early B-cell origin, but not in tumors arising from mature B-cells.

Natural attenuation of ALVAC virus in mammals makes it an attractive vector for cancer vaccine therapy of immunocompromised hosts, such as patients with lymphoid malignancies. However, the transduction efficiency of ALVAC constructs in lymphoid tumors has not yet been characterized. We studied a wide spectrum of human T- and B-cell leukemia and lymphomas and found significant heterogeneity of the ALVAC-mediated gene product expression in these tumors. While ALVAC-B7.1, ALVAC-B7.2, or ALVAC-luciferase vectors effectively expressed recombinant genes in malignancies arising from T- or early B-cell precursors, negative or low expression of ALVAC recombinant genes occurred in tumors arising from mature B-cells. We showed that ALVAC-encoded B7.1 or B7.2 was continuously expressed on the infected, and subsequently irradiated, leukemia cells, and only cells with ALVAC-mediated expression of costimulatory molecules (but not unmodified leukemia cells or those infected with the ALVAC-parental vector) induced significant proliferation and IFN-gamma production by alloreactive T-cells. These data provide the rationale for clinical studies using the ALVAC vector system for gene transfer into lymphoid tumors of T- and early B-cell origin to render them more immunogenic, while alternative strategies should be considered for immunotherapy of mature B-cell malignancies.

Enhanced sensitivity of human oral carcinomas to induction of apoptosis by selenium compounds: involvement of mitogen-activated protein kinase and Fas pathways.

Prospective studies and recent intervention trials suggest that the risk of some cancers, including respiratory tract cancers, may be inversely related to selenium (SE) intake, and this is supported by strong experimental evidence with chemical-induced animal cancer models. How this cancer-protective effect is mediated is unclear, but interference with the balance of growth/apoptosis during tumor outgrowth is one plausible hypothesis. In general, there is a correlation between the effectiveness of SE compounds as chemopreventive agents in vivo and their ability to inhibit cell growth and induce apoptosis in vitro. This study has investigated the signal transduction pathways affected by SE compounds in biopsies of normal human oral mucosa cells and human oral squamous carcinoma cells (SCCs), using a primary culture system. Two SE compounds were tested: selenodiglutathione (SDG), the primary metabolite of selenite and the most commonly used cancer-protective SE compound in animal models, and the synthetic SE compound, 1,4-phenylenebis(methylene)selenocyanate (p-XSC), one of the most potent chemopreventive pharmacological SE compounds. Three novel findings are reported: (a) SCCs were found to be significantly more sensitive to induction of apo ptosis by SDG than normal human oral mucosa cells, though the differences were marginal with p-XSC; (b) both SE compounds induced the expression of Fas ligand (Fas-L) in oral cells to a degree that correlated with the extent of apoptosis induction; and (c) both SDG and p-XSC induced the stress pathway kinases, Jun NH2-terminal kinase (JNK) and p38 kinase, at concentrations causing apoptosis; p-XSC, and to a lesser extent SDG, also activated extracellular regulated kinases 1&2 (ERKs 1&2) and protein kinase-B or Akt. To test their functional involvement, the effect of inhibiting each of these pathways on induction of apoptosis by SDG and p-XSC was determined in SCCs. Inhibiting the ERKs 1&2 or Akt pathways with specific chemical inhibitors (PD98059 or LY294002, respectively) did not affect the extent of apoptosis induced by SDG or p-XSC (with the exception of LY294002, which actually enhanced the level of induction of apoptosis by SDG). The JNK pathway appeared to be most important for induction of Fas-L and apoptosis because concentrations of SB202190 that inhibited activation of both the JNK and p38 kinase (but not ERKs 1&2) in SCC reduced the extent of induction of Fas-L and apoptosis by SDG and p-XSC, whereas lower concentrations that inhibited activation only of p38 kinase did not. This was confirmed by the fact that exogenous expression of a dominant negative deletion mutant of c-Jun (TAM67) reduced the induction of both apoptosis and Fas-L by SDG.