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Presence of additional copies of Philadelphia chromosome (Ph) is characteristic of chronic myeloid leukemia in blast crisis, very rarely observed in de novo acute lymphoblastic leukemia (ALL). Ph positive (Ph+ve) ALL and CML in lymphoid blast crisis (CML-LBC) are biologically different with divergent clinical course. Double Ph+ve ALL has little data available as to its incidence and prognostic significance. We studied five cases of Ph+ve precursor B-cell ALL having an extra copy of Ph chromosome with regard to their clinical and laboratory features. An extensive review of literature was done on prognostic significance and molecular aspects of double Ph in ALL. The study confirms that double Ph was a rare phenomenon in precursor B-cell ALL. It is observed that molecular basis of double Ph positive ALL is less understood compared to CML in blast crisis. The study highlights fundamental role of cytogenetic and molecular studies in diagnosis and management of these patients. Long-term follow-up studies on a larger group of patients are required to understand the prognostic impact of extra Ph in Ph+ve ALL, which is usually resistant to standard chemotherapeutic regimen and often requiring bone marrow transplantation., Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-022-01525-1., Competing Interests: Conflict of interestThe authors have no conflicts of interest to declare that are relevant to the content of this article., (© Indian Society of Hematology and Blood Transfusion 2022.)

Introduction: Neuroblastoma (NB), Wilms tumor (WT), hepatoblastoma (HBL), germ cell tumors (GCT), rhabdomyosarcoma (RMS), and so forth are the commonly identified solid tumors in infants. Invasive diagnostic techniques are more challenging in infants than older children. fine needle aspiration cytology (FNAC) is a safe, minimally invasive and outpatient procedure which is time and cost-effective for solid tumor diagnosis. This study aims to evaluate the role of FNAC in the diagnosis of various infantile solid tumors., Methods: In this retrospective study, 61 cases of FNA of infant solid tumors were retrieved from the cytology archives over a period of 5 years from January 2013 to December 2017. Cytomorphology was studied and immunohistochemistry on cell block was performed wherever feasible. Histopathological correlation was done in 19 cases., Results: Of the 61 cases studied, 60 cases were included in the study of which 35 were male and 25 were female. Infantile solid tumors constituted 7.3% of all pediatric solid tumors reported in cytopathology division of our Institute. The most common final diagnosis was NB (15, 25%) followed by HBL (13, 21.6%), WT (10, 16.6%), RMS (nine, 15%) and GCT (nine, 15%). The commonest site was abdominal-pelvic (42, 70%). A definitive independent diagnosis could be made on FNA in 48 cases (80%). Follow-up was done for 1.5 to 4 years (mean 26 months). The highest and lowest mortality was noted in NB (64.3%) and WT (12.5%) respectively., Conclusion: This study concludes that FNAC can be adopted as a diagnostic modality in infant solid tumors., (© 2021 Wiley Periodicals LLC.)

Synovial sarcoma is a mesenchymal neoplasm that shows a specific t(X;18) translocation that leads to the formation of SS18-SSX gene fusions and is most commonly seen in soft tissues of the extremity. The gastrointestinal tract is a very rare site of involvement. We report a case of primary gastric synovial sarcoma in a 13-year-old male child. Synovial sarcoma should be included in the differential diagnosis when spindle cell neoplasms are encountered in the stomach. A high degree of suspicion, followed by the necessary immunohistochemistry and molecular studies, is required to make an accurate diagnosis.

Background: Variety of substances such as tobacco, UV radiation, infrared rays, X-radiations, and chemicals on oral induction results in chromosomal aberrations and production of micronucleus (MN). Among them, tobacco-specific nitrosamines are potent mutagenic agents causing oral cancer., Objective: The objective of the study is to compare the genotoxicity in buccal mucosal cells, i.e. the MN count of all groups and to find the incidence of micronucleated cells (MNCs) in accordance to duration and frequency of tobacco usage and timing of contact of tobacco in the oral mucosa., Materials and Methods: Individuals without any oral diseases were divided into 3 groups having 25 in each group: smoking, chewing, and control. Smears were made from buccal exfoliated cells and stained with DNA-specific Feulgen stain. Frequency on MNC per 500 cells was assessed with one-way ANOVA and Tukey HSD multiple comparisons test and mean rank with Kruskal-Wallis test., Results: The mean micronucleus MN revealed that chewers had 8.00, smokers had 7.20 and controls had 0.4. The ANOVA test for mean frequency of micronucleated cell MNC revealed High significance (<0.001) for between groups comparison. The mean rank by Kruskal Wallis test revealed the MNC increases as the duration and frequency of habit increases. An increase in MNC in accordance to time of contact with buccal mucosa increases as the duration and time increases., Conclusion: Estimation of MN serve as an indicator of genetic damage and points that tobacco in chewing form induce genotoxic effect. This is studied in an easily accessible tissue- buccal mucosa in a non invasive manner., Competing Interests: None

Competing Interests: There are no conflicts of interest.

Tumors arising from urachus in children are exceedingly rare and sporadically reported in literature. Being a midline structure, the urachus may harbor neoplastic germ cell elements and can occasionally present as a case of acute abdomen. A 20-month-old toddler presented with spontaneous rupture of an urachal yolk sac tumor causing hemoperitoneum. He underwent resection, received platinum-based chemotherapy and presently remains well on follow-up. Despite its rarity, urachal germ cell tumors must be considered in a child with acute abdomen and tumor markers must be measured preemptively in such cases.

Background: Of the overall 9.5 million deaths annually in India, nearly 100,000 are due to organ failure. To save and extend lives, organ donation and organ transplantation have become the only hope. Health care professionals (HCPs) are a key element in facilitating cadaveric organ donation process., Objective: To assess and compare the knowledge, attitude, and practice regarding organ donation among undergraduate dental students., Methods: A cross-sectional study was conducted among 298 undergraduate dental students of the Panineeya Institute of Dental Sciences and Hospital, Hyderabad, India. A 27-item self-administered questionnaire, which assessed the levels of knowledge (Q1-13), positive attitude (Q14-24) and practice habits (Q25-27) regarding organ donation with dichotomous scale (Yes/No)., Results: As compared to males, females reported better mean±SD scores in knowledge (8.22±1.51) and practice (0.91±0.8); higher mean±SD attitude scores (8.55±1.56) were reported among males (p<0.001). While second year dental students had higher scores for their knowledge (8.55±1.56) and practice (1.02±0.44) compared to other year of training, third year students showed a significant higher mean attitude score (1.73±1.17) (p=0.02). Hindus and Muslims scored significantly lower mean knowledge, attitude and practice habits compared to others (Christians, Jains and Athesists) (p<0.001). There was a positive correlation between mean knowledge, attitude, and practice habits., Conclusion: There are an average level of knowledge and low levels of positive attitude and practice habits among studied dental students towards organ donation and transplantation.

Background: The Ewing sarcoma family of tumors (ESFT) are aggressive malignant tumors with small round cell morphology affecting mainly children and adolescents. The aim of this study is to classify the histological diversity and clinical characteristics of ESFT in children from a Tertiary Care Center in South India., Materials and Methods: This retrospective descriptive study includes 51 cases of ES in children aged below 15 years. Clinical details were collected from case files. Histomorphological features were reviewed and tumors were subtyped into classic, primitive neuroectodermal tumor (PNET) and atypical variants along with immunohistochemical markers, cytogenetics, and fluorescence in situ hybridization (FISH)., Results: Fifty-three percent were female and 47% were male with mean age of 10 years. The most common site of involvement was skeletal involvement in 71%, followed by soft tissue involvement in 23%, and visceral involvement in 6%. Localized disease at presentation was seen in 44%, locally advanced disease in 28%, and metastatic disease in 28%. Recurrence was documented during follow-up in 18% of the cases. Histomorphologically, classic type was the most common (72%) followed by PNET (20%) category and atypical variant (8%). All cases were immunoreactive for CD99. Cytogenetic study in 12 cases showed translocation t(11;22) (q24;12) in 80% and variant translocations such as t(3;16), t(3;11) with nonspecific numerical abnormalities in 20%. FISH was carried out for documentation of four cases with atypical histomorphology., Conclusion: ESFT had wide histological variation which required confirmation by ancillary studies.

Brain tumors are the second most common cancers after hematological malignancies accounting for approximate 21% of all childhood malignancies in children between ages of 0 and 14 y. The present study was undertaken to determine the spectrum of the brain tumors diagnosed in a tertiary cancer center in South India. A retrospective analysis of the data of pediatric brain tumors diagnosed between 2003 and 2009 was done and data was classified according to the age, gender and histology types. Out of 2,844 pediatric patients, 341 (11.99%) were diagnosed as having brain tumors. Most of the patients were in the age group of >5-14 y. Male to female ratio was 1.58:1. The most common pediatric brain tumor was medulloblastoma followed by astrocytoma and ependymoma. Glioblastoma multiforme was the most common subtype of astrocytoma. Other common tumors were glioma, oligodendroglioma, periphereral neuroectodermal tumor and germ cell tumor. As compared to western data, incidence of brain tumors in children was found to be less in the present study.

Introduction: The diagnosis and management of cancer in infantile age group is a significant challenge to pediatric oncologists. Malignancies occurring in infants often have different clinical and biological behavior in comparison to older children. This study was performed with an aim to find out the profile of infantile cancers at a tertiary care cancer center in South India., Methods: The present study was a retrospective analysis of infants presenting with malignancy between 2003 and 2012 to our center in South India., Result: A total of 4588 pediatric patients were registered in the Department of Pediatric Oncology at our institute between 2003 and 2012. Among those, 266 (5.79%) of the patients were infants (0-1 years). There were 65.75% males and 34.25% females. Solid tumors were the most common malignancy in this age group (72.56%). Leukemias were observed in 67 (25.19%) infants. ALL was the most common hematological malignancy (17.29%) followed by AML (5.64%). Common solid tumors in descending orders were neuroblastoma, soft tissue sarcoma, renal tumors, germ cell tumors, retinoblastoma and hepatoblastoma. Thirteen (4.89%) neonates were seen in our study. The most common malignancy in neonates was neuroblastoma., Conclusion: The distribution of malignancy in infants is quite different from that which is found in older children. Although neuroblastoma is the most common infantile tumor in western countries, in our study leukemia is the most common infantile malignancy. Embryonal tumors such as neuroblastoma, Wilms tumor, retinoblastoma, and hepatoblastoma were more prevalent in infants. Solid tumors were the most common malignancy in infants which is followed by leukemia.

Bleomycin is a chemotherapeutic antibiotic used in various malignancies. Its toxicity is mainly lung and skin with marrow sparing effect. Here we would like to describe a characteristic skin reaction developed because of bleomycin in a case of intracranial germ cell tumor. Flagellate erythema which is a self-limiting toxic reaction can cause residual hyperpigmentation.

The bio reduction of chloro auric acid (HAuCl(4)) and silver nitrate (AgNO(3)) is achieved extracellularly by using the aqueous extract of Solanum torvum (S. torvum) fruit. The nanoparticle formation was screened by UV-visible spectroscopy through color conversion due to surface plasma resonance bands at 560 nm and 430 nm for gold and silver nanoparticles respectively. The spherical shapes with smooth surface of gold and silver nanoparticles were analyzed through scanning electron microscope and its presence was confirmed by energy dispersive X-ray spectroscopy (SEM/EDX). The functional groups in the gold and silver salts and the bio interactive functional groups present in the S. torvum extract were characterized by employing Fourier transform infra-red spectroscopy (FTIR). The biomedical properties of gold and silver nanoparticles were premeditated as free radical scavenging activity and antibacterial static agents. Gold and silver nanoparticles serve as strong hydroxyl, superoxide, nitric oxide and DPPH radical scavengers in contrast to their corresponding metal oxides. The radical quenching properties of gold and silver nanoparticles were found to correlate with in vitro DNA protective effect. The silver nanoparticles show strong zone of inhibition against Escherichia coli, Pseudomonas and Bacillus whereas, gold nanoparticles exhibit fair zone of inhibition. To our knowledge this is the first report that S. torvum extract can reduce metal acids to nano materials., (Copyright © 2012 Elsevier B.V. All rights reserved.)

Aim: To assess the 1) levels of awareness and knowledge about risk factors and early signs of oral cancer among dental patients visiting dental hospital in Hyderabad city, South India 2) and to correlate the knowledge levels according to age, gender and education levels., Methods: The survey comprised of 16-item questionnaire which was distributed to patients attending Panineeya Institute of Dental Sciences, Hyderabad. Data was collected and statistically analysis was done using SPSS software (12.0 version). p<0.05 was considered statistically significant., Results: 2045 participants completed the questionnaire (response rate - 97. 9%). The reliability of the questionnaire as calculated by Cronbach's alpha was 0.75. Mean age of the study population was 37.9 years. 60.2% of the respondents had heard about oral cancer. When knowledge towards risk factors of oral cancer was taken into consideration along with variables, significant differences were seen only in gender with female having better knowledge (p=0.02). No significant difference was noted among the age group and varying education levels. However, knowledge about early signs of oral cancer revealed a highly significant difference with the level of education (p=0.000)., Conclusion: The awareness levels and knowledge about risk factors and early signs of oral cancer in this cross-section of Indian dental patients were satisfactory., (Copyright © 2011 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.)

Background: The cornerstones of successful treatment of hepatoblastoma (HB) include preoperative chemotherapy followed by complete anatomical resection of tumor, followed by chemotherapy. Advances in chemotherapy in the last 2 decades have been associated with a higher rate of tumor response and possibly a greater potential for resectability., Aims: We analyzed our single center experience with neoadjuvant chemotherapy (NACT) and surgery in HBs., Settings and Design: Our study included all children with HBs who received NACT and underwent surgical excision from January 1997 to July 2004., Materials and Methods: Patient characteristics, clinical features, clinical course, treatment modalities, and long-term outcome were analyzed., Results: There were 9 boys and 3 girls, aged 5-60 months (median age at tumor diagnosis was 24 months). All received NACT containing cisplatin and doxorubicin. Of the 12 children, 9 underwent hepatectomy and among them, 4 patients each had right and left hepatectomy and 1 patient underwent right extended hepatectomy. After surgery, all patients completed rest of the chemotherapy course (total 6 cycles). R0 resection was carried out in all the 9 cases with no life-threatening complications., Conclusions: Our experience of the 9 cases, although less in number, reaffirms the advantages of NACT followed by surgery. The prognosis for patients with resectable tumors is fairly good in combination with chemotherapy.

Background: Change in socio-economic status and various health problems adversely affect an individual's way of life during old age., Objectives: To study the health and social problems of the elderly and their attitude towards life., Materials and Methods: Descriptive study carried out in the Field practice area of the Department of Community Medicine in South India. A total of 213 elderly patients (60 years old and above) who attended the outreach clinics were interviewed using a pre-tested schedule. Findings were described in terms of proportions and percentages to study the socio-economic status of the samples and its correlation to social problems., Results: Around 73% of the patients belonged to the age group of 60-69 years old. Nearly half of the respondents were illiterate. Around 48% felt they were not happy in life. A majority of them had health problems such as hypertension followed by arthritis, diabetes, asthma, cataract, and anemia. About 68% of the patients said that the attitude of people towards the elderly was that of neglect., Conclusions: The results of the study showed that there is a need for geriatric counseling centers that can take care of their physical and psychological needs. The stringent rules for eligibility to social security schemes should be made more flexible to cover a larger population.

Purpose: Activation of polyol pathway due to increased aldose reductase (ALR2) activity has been implicated in the development of diabetic complications including diabetic retinopathy (DR), a leading cause of blindness. However, the relationship between hyperglycemia-induced activation of polyol pathway in retina and DR is still uncertain. We investigated the relationship between ALR2 levels and human DR by measuring ALR2 activity and its product, sorbitol, in erythrocytes., Methods: We enrolled 362 type 2 diabetic subjects (T2D) with and without DR and 66 normal subjects in this clinical case-control study. Clinical evaluation of DR in T2D patients was done by fundus examination. ALR2 activity and sorbitol levels along with glucose and glycosylated hemoglobin (HbA1C) levels in erythrocytes were determined., Results: T2D patients with DR showed significantly higher specific activity of ALR2 as compared to T2D patients without DR. Elevated levels of sorbitol in T2D patients with DR, as compared to T2D patients without DR, corroborated the increased ALR2 activity in erythrocytes of DR patients. However, the increased ALR2 activity was not significantly associated with diabetes duration, age, and HbA1C in both the DR group and total T2D subjects., Conclusions: Levels of ALR2 activity as well as sorbitol in erythrocytes may have value as a quantitative trait to be included among other markers to establish a risk profile for development of DR.

Pediatric small round cell tumors (SRCT) are a group of neoplasms occurring in children, which have in common a cytomorphology of groups of small round cells with scanty cytoplasm. The common SRCT encountered are neuroblastoma, retinoblastoma, Ewing's sarcoma/peripheral neuroectodermal tumor (PNET), rhabdomyosarcoma and lymphoma which show varying degrees of bone marrow involvement and bone marrow evaluation forms a part of the initial staging procedure. This study was undertaken to evaluate marrow involvement at presentation in pediatric non hematological SRCT. 7833 bone marrow aspirates done over a period of three years in different malignancies were analysed and of these 180 aspirates were performed in patients of pediatric non hematological SRCT at presentation. These cases were evaluated in detail for incidence of marrow involvement. Thirty two (17.7%) cases showed marrow involvement and these cases have been analysed with respect to the primary tumor. The SRCT showing involvement of bone marrow included neuroblastoma (48.8%), retinoblastoma (11.1%), Ewing's sarcoma/PNET (8.6%) and rhabdomyosarcoma (3.2%). These findings are discussed in the light of available world literature.

Background & Objective: Detection of AmpC-mediated resistance in Gram-negative organisms poses a problem due to misleading results in phenotypic tests. There are no recommended guidelines for detection of this resistance mechanism and there is a need to address this issue as much as the detection of extended spectrum beta lactamases (ESBLs) since both may co-exist and mask each other. Though resistance to cefoxitin is used as a screening test, it does not reliably indicate Amp C production. This study was undertaken to detect Amp C beta lactamases in certain Gram-negative bacteria employing an inhibitor base test using boronic acid., Methods: A total number of 76 consecutive non repetitive clinical isolates of Escherichia coli (n=67) and 9 Klebsiella pneumoniae (n=9) obtained over a period of two months, were screened for amp C production by disc diffusion method using cefoxitin (30 microg) dics and confirmed by inhibitor based test using boronic acid as inhibitor., Results: A total of 36 of 76 isolates (47.3%) screened harboured amp C enzymes, of which a majority 31 (86.1%) co-produced ESBL enzymes. Pure ampC production was seen in 7 (9.2%) of isolates only., Interpretation & Conclusion: Most of the amp C producers also produced ESBL enzymes. The inhibitor based test was useful in identifying cefoxitin susceptible amp C producers and could also effectively differenciate ESBL from amp C producing isolates.

Ascariasis is caused by the roundworm, Ascaris lumbricoides. We report an additional case of live Ascaris lumbricoides removed from the lacrimal puncta of a 10-year-old boy.

Cis-unsaturated fatty acids (c-UFAs) have been shown to be capable of decreasing the survival of macrophage tumor (AK-5) cells in vitro. This cytotoxic action of c-UFAs was found to be associated with an increase in free radical generation and lipid peroxidation process and a simultaneous decrease in cellular anti-oxidants such as superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione reductase, glutathione and vitamin E. In the present study, it was observed that c-UFAs such as gamma linolenic acid (GLA), arachidonic acid (AA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can activate phospholipase C (PLC) and enhance diacylglycerol formation; all the fatty acids except alpha linolenic acid (ALA) increased the binding of phorbol dibutyrate acetate (PDBu) suggesting translocation of protein kinase C (PKC) and at the same time these fatty acids (especially GLA, AA, EPA and DHA) also enhanced PKC activity. AA, EPA and DHA decreased the activity of protein kinase A (PKA) both in the cytosol and particulate fractions whereas ALA and GLA enhanced the PKA activity in the particulate fractions; all the fatty acids except ALA reduced cyclic AMP levels and an enhanced phosphorylation of about 13 proteins of the nuclear fraction and about eight proteins of the plasma membrane fraction was noted in c-UFA treated AK-5 cells in vitro. These results suggest that c-UFAs can alter the activities of second messenger systems such as diacylglycerol and protein kinases and can phosphorylate both plasma membrane and nuclear proteins which are likely to be components of NADPH oxidase. Based on these results, it is suggested that fatty acids may mediate their cytotoxic action in part by modulating the expression of PKC. Activated PKC may then intensify the pro-oxidant state by augmenting NADPH oxidase, so inducing superoxide anion generation which may ultimately lead to cytolysis.

Tumour cell drug resistance is a major problem in cancer chemotherapy. Essential fatty acids have been shown to be cytotoxic to a variety of tumour cells in vitro. But, the effect of these fatty acids on tumour cell drug resistance has not been well characterized. Gamma-linolenic acid (GLA) of the n-6 series and eicosapentaenoic acid (EPA) of the n-3 series potentiated the cytotoxicity of anti-cancer drugs: vincristine, cis-platinum and doxorubicin on human cervical carcinoma (HeLa) cells in vitro. Alpha-linolenic acid (ALA), GLA, EPA and docosahexaenoic acid (DHA) enhanced the uptake of vincristine by HeLa cells. In addition, DHA, EPA, GLA and DGLA were found to be cytotoxic to both vincristine-sensitive (KB-3-1) and -resistant (KB-ChR-8-5) human cervical carcinoma cells in vitro. Pre-incubation of vincristine-resistant cells with sub-optimal doses of fatty acids enhanced the cytotoxic action of vincristine. GLA, DGLA, AA, EPA and DHA enhanced the uptake and inhibited the efflux of vincristine and thus, augmented the intracellular concentration of the anti-cancer drug(s). Fatty acid analysis of KB-3-1 and KB-ChR-8-5 cells showed that the latter contained low amounts of ALA, GLA, 22:5 n-3 and DHA in comparison to the vincristine-sensitive cells. The concentrations of GLA and DHA were increased 10-15 fold in the phospholipid, free fatty acid and ether lipid cellular lipid pools of GLA and DHA treated cells. These results coupled with the observation that various fatty acids can alter the activity of cell membrane bound enzymes such as sodium-potassium-ATPase and 5'-nucleotidase, levels of various anti-oxidants, p53 expression and the concentrations of protein kinase C suggest that essential fatty acids and their metabolites can reverse tumour cell drug-resistance at least in vitro.

Cis-unsaturated fatty acids (c-UFAs) induced decreased survival of macrophage tumor (AK-5) cells in vitro. The cytotoxic action of c-UfAs was associated with an increase in free radical generation and lipid peroxidation process. In addition, exposure of AK-5 cells to various c-UFAs for a short period (1 h) decreased the cellular concentrations of anti-oxidants: superoxide dismutase (SOD), catalase, glutathione peroxidase, glutathione reductase, glutathione and vitamin E. However, prolonged (24 h) exposure of AK-5 cells to c-UFAs enhanced the levels of SOD with little or no change in the concentrations of catalase, glutathione peroxidase and glutathione reductase. These results indicate that c-UFAs can enhance free radical generation and lower the concentrations of various anti-oxidants in the tumor cells which may explain the cytotoxic action of c-UFAs.

Prostacyclin (PGI2) prevented genetic damage to the bone marrow cells of mice induced by gamma-radiation, benzo(a)pyrene(BP) and cis-platinum(cis-DDP). Carba-PGI2, an analogue of PGI2, was also effective against cis-DDP-induced mutagenicity. In a time-course study it was observed that the geno-protective action of PGI2, can last as long as 24 hr. 6-keto-PGF1 alpha, a major metabolite of PGI2 and c-AMP, a second messenger, were ineffective in bringing about this beneficial action. PGI2 did not influence free radical generation induced by phorbol myristate acetate in human peripheral leukocytes. This suggests that the genoprotective action of PGI2 is not mediated by its metabolite 6-keto-PGF1 alpha and the second messenger cyclic-AMP and is not due to any action on free radical generation. This geno-protective action of PGI2 would be futile if it interfered with the tumoricidal action of cis-DDP. It was observed that the cytotoxic action of cis-DDP against Meth-A tumor cells was not interfered with by PGI2 and carba-PGI2 both in vitro and in vivo. This description of the geno-protective action of PGI2 is important in the development of new strategies in cancer chemotherapy since, it is likely that anticancer drugs, at least cis-DDP can be given along with PGI2 to prevent genetic damage to normal cells without interfering with their tumoricidal action.

An earlier study showed that essential fatty acids and their metabolites can kill tumor cells in vitro. This tumoricidal action can be correlated to an increase in generation of free radicals in the tumor cells. Evening primrose oil (EPO) is a rich source of linoleic acid and gamma-linolenic acid. We report that EPO can kill tumor cells both in vitro and in vivo. This tumoricidal action of EPO was associated with a threefold increase in superoxide generation. One of the factors that is capable of interfering with the cytotoxic action of fatty acids appears to be the protein content of the medium. Fatty acids can bind to protein and thus prevent their cytotoxic action.

Psoriasis is a common disorder characterized by marked increases in keratinocyte proliferation, abnormal patterns of keratinocyte differentiation, prominent alterations in dermal capillary vasculature and the presence of dermal and epidermal T cells, monocytes/macrophages and neutrophils. It is now known that psoriasis can occur due to abnormalities in essential fatty acid metabolism, lymphokine secretion, free radical generation, lipid peroxidation and eicosanoid metabolism. It is possible to suppress almost completely psoriatic lesions by judicious use of methotrexate, cyclosporine A, and eicosapentaenoic acid. Our studies have shown that in patients with psoriasis there is an increase in the generation of free radicals with an alteration in essential fatty acid metabolism and that side-effects of anti-cancer drugs can be blocked by essential fatty acids in vivo. Thus, essential fatty acid metabolism seems to play a crucial role both in the pathogenesis and treatment of psoriasis.

Specific fatty acids such as linoleic acid (LA), gamma-linolenic acid (GLA), dihomo gamma linolenic acid (DGLA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) showed cytotoxicity towards human cervical (HeLa) cells in vitro. Cyclo-oxygenase inhibitor, indomethacin; lipoxygenase inhibitor, nordihydroguiaretic acid (NDGA); anti-oxidant, vitamin E; and calmodulin antagonists, trifluoperazine (TFP) and chlorpromazine (CPZ) blocked the cytotoxic action of these fatty acids. GLA-induced free radical generation and lipid peroxidation were also inhibited by indomethacin, NDGA, vitamin E, TFP and CPZ. Both indomethacin and NDGA also showed significant anti-oxidant property. These results suggest that fatty acid-induced cytotoxic action against HeLa cells is a free radical dependent process and that it can be modulated by calmodulin antagonists. These results are in contrast to those observed by us earlier with human breast cancer cells where in it was found that the tumoricidal action of fatty acids can be blocked by anti-oxidants but not by cyclo-oxygenase (CO) and lipoxygenase (LO) inhibitors. From these results it can be suggested that though free radicals are the mediators of the tumoricidal action of fatty acids, the mechanism of their production may be different in different types of tumor cells.

The mechanism(s) involved in the generation of free radicals in human leukocytes by phorbol myristate acetate (PMA), formyl-methionyl-leucyl-phenylalanine (FMP), lipopolysaccharide (LPS), arachidonic acid (AA), and recombinant-tumor necrosis factor-1-alpha (r-TNF-1 alpha) was investigated. Calmodulin antagonists, chlorpromazine and trifluoperazine, inhibited free radical generation in human leukocytes by these stimulants. Dexamethosone, an inhibitor of phospholipase A2, could also block free radical generation in human leukocytes induced by r-TNF 1 alpha. PMA, FMP, LPS and TNF can activate phospholipase A2 and induce the release of AA from the cell membrane lipid pool. AA induced free radical generation in human leukocytes can be inhibited by calmodulin antagonists. Hence, it is likely that calmodulin dependent events play a crucial role in the generation of free radicals by human leukocytes in response to various stimulants including TNF.