Optimizing Tissue Harvesting Techniques for Establishing Patient-Derived Glioblastoma Organoids.

INTRODUCTION: Brain tumors display remarkable cellular and molecular diversity, significantly impacting the progression and outcomes of the disease. The utilization of tumor tissue acquired through surgical handheld devices for tumor characterization raises important questions regarding translational research. This study seeks to evaluate the integrity of tissue resected using a microdebrider(MD) in the context of establishing tumor organoids from glioblastomas(GBM). METHODS: Tumor samples were collected from patients with GBM using both tumor forceps(en bloc) and a MD(Myriad;Nico,Corp.). The time required to protocol completion and cell viability of paired samples were measured. H&E staining was performed to examine histological morphology. RESULTS: Ten paired samples were obtained from GBM patients using tumor forceps and the MD. Samples collected with the MD demonstrated significantly shorter processing times compared to those obtained through en bloc resection, with overall means of 31.7±2.4mins and 38.8±3mins, respectively(p<0.001). Cell viability measured at the end of protocol completion was comparable between tissues obtained using both the MD and en bloc, with mean viabilities of 80.2±12.4% and 79.1±12.5%, respectively(p=0.848). H&E examination of tissues revealed no significant differences in the cellular and histological characteristics of paired samples obtained using both methods across GBM tumors, nor in the corresponding established organoids. CONCLUSION: Tumor tissues obtained using the MD and en bloc methods demonstrate a high success rate in establishing GBM organoids, with the MD offering the advantage of significantly reduced processing time. Both methods display comparable cell viability and maintain consistent histological characteristics in the resected tissue and the corresponding organoids.

Comparison of Resection Assisting Devices in the Process of Collecting Brain Tumor Tissue for Basic Research: Microdebrider Versus Ultrasonic Aspirator.

INTRODUCTION: Brain tumors display significant inter and intratumoral heterogeneity, impacting disease progression and outcomes. Preserving surgically resected tissue is vital for ensuring accurate research results to enhance understanding of tumor pathophysiology. This study evaluates tissue integrity and viability of tissue resected using 2 surgical devices for tumor resection: a mechanical microdebrider (MD) and an ultrasonic aspirator (UA). METHODS: Tumor samples were obtained from patients undergoing surgical resection of primary and secondary intracranial tumors. Cell viability was assessed, and histopathological analysis of Hematoxylin and Eosin -stained tissues was performed. Adherent monolayer and neurospheres cell cultures were established from paired samples. RNA isolation and quantitative polymerase chain reaction of housekeeping genes were conducted to compare genetic integrity. RESULTS: The cellular viability was comparable between samples obtained using both the MD and the UA, with a mean viability of 75.2% ± 15.6 and 70.7% ± 16.8, respectively (P = 0.318). Histopathological evaluation indicated no discernible differences in cellular integrity between the devices. Cell culture success rates and growth characteristics were similar for both devices. RNA concentration and integrity were well-maintained in both MD and UA samples, with no significant differences (P = 0.855). Quantitative polymerase chain reaction analysis of housekeeping genes showed consistent results across matched tissues from both devices and different tumor pathologies. CONCLUSIONS: Surgical handheld devices provide valuable, high-quality tissue samples for research. Surgeon preference, tumor pathology, and anatomical location dictate device choice. Both MD and UA devices are reliable for obtaining quality tissue specimens, facilitating translational neuro-oncology research.

BA.5 bivalent booster vaccination enhances neutralization of XBB.1.5, XBB.1.16 and XBB.1.9 variants in patients with lung cancer.

This study reports that most patients with NSCLC had a significant increase in the nAb response to the currently circulating Omicron variants after bivalent booster vaccination and had Ab titers comparable to healthy participants. Interestingly, though the durability of the nAb response persisted in most of the healthy participants, patients with NSCLC had significantly reduced nAb titers after 4-6 months of vaccination. Our data highlight the importance of COVID-19 bivalent booster vaccination as the standard of care for patients with NSCLC given the evolution of new variants of concern.

Haploidentical Transplant in Radiosensitive Severe Combined Immunodeficiency Disease.

Severe combined immunodeficiency (SCID) is an inborn error of immunity invariably resulting in mortality in infancy until managed by hematopoietic stem cell transplant (HSCT). We present an unusual case of SCID with a rare mutation involving the non-homologous end-joining 1 (NHEJ1) gene, where a haploidentical HSCT was carried out with modified conditioning and graft versus host prophylaxis regimen using proteasome inhibitor bortezomib with a successful outcome.

Psychosocial issues among paediatric health-care workers posted in intensive care unit during COVID-19 pandemic: A questionnaire-based survey (Psy-Co-19 survey).

AIM: To understand the moral distress experienced by health-care workers (HCWs) in the COVID paediatric intensive care unit (PICU). We also aimed to assess the psychological well-being and the coping mechanisms used by HCWs. METHODS: A prospective observational cross-sectional study was conducted from July to September 2021, involving all HCWs who worked in the COVID PICU. Moral distress using Moral Distress for Health-care Professionals (MMD-HPs) scale, psychological well-being using Trauma Screening Questionnaire (TSQ) and coping strategies adopted by HCWs using Brief-COPE (Coping Orientation to Problems Experienced) were measured. RESULTS: One hundred and eighty-four HCW data were examined. The most common causes of moral distress among HCWs were compromised patient care caused by a lack of resources and caring for more patients than they could safely handle. Moral distress was the same regardless of the HCWs' job profile, marital status, number of children or age. The TSQ revealed psychological stress in 23.3% of HCWs with Post-traumatic Stress Disorder, significantly higher in HCWs under the age of 30 and without children. Few HCWs turned to substance use, self-blame or denial as coping mechanisms; instead, acceptance, self-distraction and emotional support were the most frequently used. CONCLUSION: The most common reasons for moral and psychological distress perceived by participants were insufficient staff and organisational support. Younger HCWs and those without children experienced higher levels of psychological distress. HCWs' typical coping mechanisms are constructive, such as seeking help and support from others, reframing situations and meditation. Health-care administrators must develop a framework to assist HCWs in dealing with such serious issues.

Multifocal Multisystem Langerhans Cell Histiocytosis Involving Pituitary Masquerading as Crohn's Disease: A Case Report and Review of the Literature.

Background/Objective. We present a case of Langerhans cell histiocytosis (LCH) with gastrointestinal involvement masquerading as inflammatory bowel disease (IBD) in a patient who initially had features of central diabetes insipidus (CDI). Case Report. A 19-year-old male presented at 14 years of age with central diabetes insipidus. He subsequently developed panhypopituitarism and sellar-suprasellar mass, the biopsy of which was inconclusive. Secondary causes for hypophysitis were ruled out. Five years later, he developed perianal pus discharging sinuses, positive ASCA, and sacroiliitis. Rectal ulcer biopsy showed nonspecific inflammation and necrosis. Hence, he was managed as inflammatory bowel disease (IBD). Due to nonresponsiveness of symptoms, doubt about diagnosis was invoked and rectal ulcer biopsy was repeated, which then showed infiltration by Langerhans cells. Hence, he was diagnosed with LCH and showed resolution of symptoms on initiating steroids and vinblastine. Discussion. Gastrointestinal involvement by LCH is unusual and only rarely has represented a prominent clinical manifestation. In most cases, such involvement suggests widespread multisystem disease. Its distinctive morphologic and immunohistochemical features allow LCH to be distinguished from other inflammatory infiltrations found in mucosal biopsy specimens. Conclusion. Preceding CDI and hypopituitarism may predict LCH in patients with IBD-like diseases.

Antibody Response to COVID-19 mRNA Vaccine in Patients With Lung Cancer After Primary Immunization and Booster: Reactivity to the SARS-CoV-2 WT Virus and Omicron Variant.

PURPOSE: To examine COVID-19 mRNA vaccine-induced binding and neutralizing antibody responses in patients with non-small-cell lung cancer (NSCLC) to SARS-CoV-2 614D (wild type [WT]) strain and variants of concern after the primary 2-dose and booster vaccination. METHODS: Eighty-two patients with NSCLC and 53 healthy volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2-specific binding and neutralizing antibody responses were evaluated by Meso Scale Discovery assay and live virus Focus Reduction Neutralization Assay, respectively. RESULTS: A majority of patients with NSCLC generated binding and neutralizing antibody titers comparable with the healthy vaccinees after mRNA vaccination, but a subset of patients with NSCLC (25%) made poor responses, resulting in overall lower (six- to seven-fold) titers compared with the healthy cohort (P = < .0001). Although patients age > 70 years had lower immunoglobulin G titers (P = < .01), patients receiving programmed death-1 monotherapy, chemotherapy, or a combination of both did not have a significant impact on the antibody response. Neutralizing antibody titers to the B.1.617.2 (Delta), B.1.351 (Beta), and in particular, B.1.1.529 (Omicron) variants were significantly lower (P = < .0001) compared with the 614D (WT) strain. Booster vaccination led to a significant increase (P = .0001) in the binding and neutralizing antibody titers to the WT and Omicron variant. However, 2-4 months after the booster, we observed a five- to seven-fold decrease in neutralizing titers to WT and Omicron viruses. CONCLUSION: A subset of patients with NSCLC responded poorly to the SARS-CoV-2 mRNA vaccination and had low neutralizing antibodies to the B.1.1.529 Omicron variant. Booster vaccination increased binding and neutralizing antibody titers to Omicron, but antibody titers declined after 3 months. These data highlight the concern for patients with cancer given the rapid spread of SARS-CoV-2 Omicron variant.

A Targeted Metabolomics Approach to Study Secondary Metabolites and Antioxidant Activity in 'Kinnow Mandarin' during Advanced Fruit Maturity.

In this study, we investigated the impact of harvest maturity stages and contrasting growing climates on secondary metabolites in Kinnow mandarin. Fruit samples were harvested at six harvest maturity stages (M1−M6) from two distinct growing locations falling under subtropical−arid (STA) and subtropical−humid (STH) climates. A high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) technique was employed to identify and quantify secondary metabolites in the fruit juice. A total of 31 polyphenolics and 4 limonoids, with significant differences (p < 0.05) in their concentration, were determined. With advancing maturity, phenolic acids and antioxidant activity were found to increase, whereas flavonoids and limonoids decreased in concentration. There was a transient increase in the concentration of some polyphenolics such as hesperidin, naringin, narirutin, naringenin, neoeriocitrin, rutin, nobiletin and tangeretin, and limonoid aglycones such as limonin and nomilin at mid-maturity stage (M3) which coincided with prevailing low temperature and frost events at growing locations. A higher concentration of limonin and polyphenolics was observed for fruit grown under STH climates in comparison to those grown under STA climates. The data indicate that fruit metabolism during advanced stages of maturation under distinct climatic conditions is fundamental to the flavor, nutrition and processing quality of Kinnow mandarin. This information can help in understanding the optimum maturity stage and preferable climate to source fruits with maximum functional compounds, less bitterness and high consumer acceptability.

The Study of Pattern of Lipid Profile in Chronic Kidney Disease Patients on Conservative Management and Hemodialysis: A Comparative Study.

BACKGROUND: Chronic kidney disease (CKD) causes irreversible damage to the renal tissue resulting in decreased kidney function. It is known more for its morbidity than for its mortality as the deranged kidney functioning affects almost every organ system of the body. Dyslipidemia is one of the most common complications of chronic renal failure (CRF) reflected even in the early stages of CRF and usually parallels the deterioration in renal function. As a consequence, dyslipidemia as a risk factor in CKD progression should be explored and documented more. The aim of the study was to compare the pattern of lipid profile in CKD patients on conservative management with that of CKD patients on hemodialysis. MATERIALS AND METHODS: This is a cross-sectional observational study conducted in Lucknow, India, between January 2021 to May 2021 after considering inclusion and exclusion criteria. The lipid profile of 105 eligible patients was analyzed using an autoanalyzer. After generation of the proper template, data was entered in Microsoft Excel (Microsoft Corp., Redmond, Washington, United States) and analysis was done through SPSS for Windows, Version 16.0 (Released 2007, SPSS Inc., Chicago, United States). RESULTS: There was a statistically significant decrease in high-density lipoprotein (HDL) and an increase in triglycerides (TG) and very-low-density lipoprotein (VLDL) levels in CKD patients on hemodialysis when compared with CKD patients on conservative management. As far as total cholesterol and low-density lipoprotein (LDL) levels are concerned, they were also significantly increased in CKD patients on hemodialysis than CKD patients on conservative management. CONCLUSIONS: Dyslipidemia progresses with the stage of CKD, so early monitoring of lipid profile in CKD patients may help in decreasing the progression of the disease and, hence, mortality in CKD patients.

Antibody response to SARS-CoV-2 mRNA vaccine in lung cancer patients: Reactivity to vaccine antigen and variants of concern.

PURPOSE: We investigated SARS-CoV-2 mRNA vaccine-induced binding and live-virus neutralizing antibody response in NSCLC patients to the SARS-CoV-2 wild type strain and the emerging Delta and Omicron variants. METHODS: 82 NSCLC patients and 53 healthy adult volunteers who received SARS-CoV-2 mRNA vaccines were included in the study. Blood was collected longitudinally, and SARS-CoV-2-specific binding and live-virus neutralization response to 614D (WT), B.1.617.2 (Delta), B.1.351 (Beta) and B.1.1.529 (Omicron) variants were evaluated by Meso Scale Discovery (MSD) assay and Focus Reduction Neutralization Assay (FRNT) respectively. We determined the longevity and persistence of vaccine-induced antibody response in NSCLC patients. The effect of vaccine-type, age, gender, race and cancer therapy on the antibody response was evaluated. RESULTS: Binding antibody titer to the mRNA vaccines were lower in the NSCLC patients compared to the healthy volunteers (P=<0.0001). More importantly, NSCLC patients had reduced live-virus neutralizing activity compared to the healthy vaccinees (P=<0.0001). Spike and RBD-specific binding IgG titers peaked after a week following the second vaccine dose and declined after six months (P=<0.001). While patients >70 years had lower IgG titers (P=<0.01), patients receiving either PD-1 monotherapy, chemotherapy or a combination of both did not have a significant impact on the antibody response. Binding antibody titers to the Delta and Beta variants were lower compared to the WT strain (P=<0.0001). Importantly, we observed significantly lower FRNT50 titers to Delta (6-fold), and Omicron (79-fold) variants (P=<0.0001) in NSCLC patients. CONCLUSIONS: Binding and live-virus neutralizing antibody titers to SARS-CoV-2 mRNA vaccines in NSCLC patients were lower than the healthy vaccinees, with significantly lower live-virus neutralization of B.1.617.2 (Delta), and more importantly, the B.1.1.529 (Omicron) variant compared to the wild-type strain. These data highlight the concern for cancer patients given the rapid spread of SARS-CoV-2 Omicron variant.

Antibody binding and neutralization of live SARS-CoV-2 variants including BA.4/5 following booster vaccination of patients with B-cell malignancies.

Non-Hodgkin lymphoma and chronic lymphocytic leukemia (NHL/CLL) patients elicit inadequate antibody responses after initial SARS-CoV-2 vaccination and remain at high risk of severe COVID-19 disease. We investigated IgG, IgA, and IgM responses after booster vaccination against recent SARS-CoV-2 variants including Omicron BA.5 in 67 patients. Patients had lower fold increase and total anti-spike binding titers after booster than healthy individuals. Antibody responses negatively correlated with recent anti-CD20 therapy and low B cell numbers. Antibodies generated after booster demonstrated similar binding properties against SARS-CoV-2 variants compared to those generated by healthy controls with lower binding against Omicron variants. Importantly, 43% of patients showed anti-Omicron BA.1 neutralizing antibodies after booster and all these patients also had anti-Omicron BA.5 neutralizing antibodies. NHL/CLL patients demonstrated inferior antibody responses after booster vaccination, particularly against Omicron variants. Prioritization of prophylactic and treatment agents and vaccination of patients and close contacts with updated vaccine formulations are essential.

Lipid Profile in Pre-dialysis and Post-dialysis End Stage Renal Disease Patients: A Cross-Sectional Comparative Study in Lucknow, India.

BACKGROUND: Chronic kidney disease (CKD) patients are at elevated risk of cardiovascular diseases (CVD) due to altered lipid profiles. Dyslipidemia is maximal in end stage renal disease (ESRD) patients and there is insufficient data on the impact of hemodialysis on lipid profile. The present study was aimed to evaluate the effect of hemodialysis on lipid profile of CKD patients. MATERIALS AND METHODS: This cross-sectional study was conducted on 50 CKD patients on hemodialysis from three randomly selected hospitals of Lucknow, Uttar Pradesh, India, between March - May 2021. Serum lipid profile was analysed before and after hemodialysis session by using an auto analyzer. The mean values of different lipid parameters before and after hemodialysis were calculated and the difference between them was analyzed by using paired t-test. A p-value of <0.05 was considered to be statistically significant. RESULTS: In this study, very low density lipoprotein (VLDL) levels decreased significantly after hemodialysis. Total cholesterol (TC), low density lipoprotein (LDL) and triglyceride (TG) levels were also significantly lowered. High density lipoprotein (HDL) was the only lipoprotein that increased after dialysis although this increase was non-significant. CONCLUSION: Adequate dialysis and time bound monitoring of various components of lipid profile can help CKD patients by decreasing risks for cardiovascular complications.

Promoting Inuit health through a participatory whiteboard video.

SETTING: The Inuit community of Rigolet experiences greater rates of self-reported acute gastrointestinal illness (AGI) compared to southern Canada. INTERVENTION: A whiteboard video tool was collaboratively developed by Rigolet youth, community members, the research team and key regional stakeholders to share public health recommendations for reducing the risk of AGI. The video debuted in Rigolet at a community event in August 2016 and was later provided online for community members and local and regional health departments. Interviews and focus group discussions were used to evaluate the ability of the video to communicate public health information to community members in Rigolet. OUTCOMES: Community and government viewers reported that the whiteboard video was novel and engaging. Evaluation participants believed the video was suitable for promoting Inuit health because of the use of locally relevant visuals and narrative, which reflect Inuit art and storytelling traditions. Furthermore, participants indicated that the video co-development process was critical to ensuring community relevance of the video. Short-term outcome results suggest the video can reinforce health knowledge and potentially encourage behavioural change. IMPLICATIONS: The results suggest this whiteboard video was an effective tool to share information and could increase intention to change behaviours to reduce the risk of AGI in Rigolet. While tools like the whiteboard video are gaining popularity, the participatory approach was used to develop the video, and its use in an Inuit context illustrates its innovation and novelty. This tool may be a useful health promotion tool among Indigenous communities in Canada.

Targeted metabolite profiling to gain chemometric insight into Indian pomegranate cultivars and elite germplasm.

BACKGROUND: Pomegranate fruit is an excellent source of bioactive polyphenolics, known to contribute significantly to human health. India is the largest producer of pomegranate in the world and produces the finest quality fruit with highly desirable consumer traits such as soft seeds, low acidity, and attractive fruit and aril color. Knowledge of the extent of variation in key metabolites (sugars, organic acids, phenolics, and anthocyanins) is key to selecting superior genotypes for germplasm improvement. Relevant information with respect to Indian genotypes is scarce. The present study therefore aims to evaluate quantitatively important metabolites in some cultivars and elite germplasm of pomegranate in India. RESULTS: Identification and quantification of primary and secondary metabolites such as sugars, organic acids, vitamin C, polyphenolics, and anthocyanins were conducted using a liquid chromatography - mass spectrometry (LC-MS) platform. Fructose and citric acid were the predominant sugar and organic acid, respectively. Wild genotypes had significantly higher concentrations of organic acids, antioxidant activity, and phenolics, namely punicalagin, ellagic acid, sinapic, and ferulic acid. CONCLUSION: Cyanidin and delphinidin derivatives of anthocyanins were more abundant in red aril commercial genotypes. Results suggest that wild-sour accessions represent a rich source of polyphenolics that can be utilized in future breeding programs to breed healthier varieties, food supplements, and pharmaceutical products. © 2019 Society of Chemical Industry.

Participatory methods for Inuit public health promotion and programme evaluation in Nunatsiavut, Canada.

Engaging stakeholders is crucial for health promotion and programme evaluations; understanding how to best engage stakeholders is less clear, especially within Indigenous communities. The objectives of this thesis research were to use participatory methods to: (1) co-develop and evaluate a whiteboard video for use as a public health promotion tool in Rigolet, Nunatsiavut, and (2) develop and validate a framework for participatory evaluation of Inuit public health initiatives in Nunatsiavut, Labrador. Data collection tools included interactive workshops, community events, interviews, focus-group discussions and surveys. Results indicated the whiteboard video was an engaging and suitable medium for sharing public health messaging due to its contextually relevant elements. Participants identified 4 foundational evaluation framework components necessary to conduct appropriate evaluations, including: (1) community engagement, (2) collaborative evaluation development, (3) tailored evaluation data collection and (4) evaluation scope. This research illustrates stakeholder participation is critical to develop and evaluate contextually relevant public health initiatives in Nunatsiavut, Labrador and should be considered in other Indigenous communities.

Cell cycle regulation and apoptotic cell death in experimental colon carcinogenesis: intervening with cyclooxygenase-2 inhibitors.

Relative imbalance in the pathways regulating cell cycle, cell proliferation, or cell death marks a prerequisite for neoplasm. C-phycocyanin, a biliprotein from Spirulina platensis and a selective COX-2 inhibitor along with piroxicam, a traditional nonsteroidal antiinflammatory drug was used to investigate the role of cell cycle regulatory proteins and proinflammatory transcription factor NFκB in 1,2-dimethylhydrazine dihydrochloride (DMH)-induced rat colon carcinogenesis. Cell cycle regulators [cyclin D1, cyclin E, cyclin dependent kinase 2 (CDK2), CDK4, and p53], NFκB (p65) pathway, and proliferating cell nuclear antigen (PCNA) were evaluated by gene and protein expression, whereas apoptosis was studied by terminal deoxynucleotidyl transferase dUTP nick end labeling and apoptotic bleb assay. Molecular docking of ligand protein interaction was done to validate the in vivo results. Cyclin D1, cyclin E, CDK2, and CDK4 were overexpressed in DMH, whereas piroxicam and c-phycocyanin promoted the cell cycle arrest by downregulating them. Both drugs mediated apoptosis through p53 activation. Piroxicam and c-phycocyanin also stimulated antiproliferation by restraining PCNA expression and reduced cell survival via inhibiting NFκB (p65) pathway. Molecular docking revealed that phycocyanobilin (a chromophore of c-phycocyanin) interact with DNA binding site of NFκB. Inhibition of cyclin/CDK complex by piroxicam and c-phycocyanin affects the expression of p53 in colon cancer followed by downregulation of NFκB and PCNA levels, thus substantiating the antineoplastic role of these agents.

Postharvest vapour heat treatment as a phytosanitary measure influences the aroma volatiles profile of mango fruit.

Our objective was to determine the influence of postharvest vapour heat treatment (VHT) on qualitative and quantitative measurement of aroma volatiles during fruit ripening in mango (cv. Chausa) using gas chromatography-mass spectrometry (GC-MS). VHT (48°C for 20 min) accelerated the process of fruit ripening leading to edible-soft stage within 4 days after heat treatment against 8 days in control. Reversible inhibition of aroma volatiles emission was observed in heat-treated fruit, with a significant alteration in aroma volatiles profiles at different stages of fruit ripening. The heat-induced increase in the rate of fruit ripening proceeded with a significant lag in the emission of aroma volatiles. The suppression of aroma volatiles at ripe stage in heat-treated fruit might adversely impact the consumer acceptance of fruit.

Targeting angiogenic pathway for chemoprevention of experimental colon cancer using C-phycocyanin as cyclooxygenase-2 inhibitor.

An angiogenic pathway was studied that involved stromal tissue degradation with matrix metalloproteinases (MMPs), vesicular endothelial growth factor-A (VEGF-A), and hypoxia inducible factor-1α (HIF-1α) mediated growth regulation in a complex interaction with chemokines, such as monocyte chemoattractant protein-1 (MCP-1) and macrophage inflammatory protein-1ß (MIP-1ß). Gene and protein expression was studied with real-time PCR, Western immunoblot, and immunofluorescence. Morphological and histopathological analysis of tumor was done, as also the activity of MMPs and HIF-1α by gelatin zymography and ELISA. Binding interactions of proteins were studied by molecular docking. Piroxicam, a traditional NSAID and C-phycocyanin, a biliprotein from Spirulina platensis, were utilized in the chemoprevention of DMH-induced rat colon cancer. A significant number of tumors was evident in DMH treated animals, while with piroxicam and C-phycocyanin, the number and size of tumors/lesions were reduced. Colonic tissues showed severe dysplasia, tubular adenoma, and adenocarcinoma from DMH, with invasive features along with signet ring cell carcinoma. No occurrence of carcinoma was detected in either of the drug treatments or in a combination regimen. An elevated VEGF-A, MMP-2, and MMP-9 level was observed, which is required for metastasis and invasion into surrounding tissues. Drugs induced chemoprevention by down-regulating these proteins. Piroxicam docked in VEGF-A binding site of VEGF-A receptors i.e., VEGFR1 and VEGFR2, while phycocyanobilin (a chromophore of C-phycocyanin) docked with VEGFR1 alone. HIF-1α is up-regulated which is associated with increased oxygen demand and angiogenesis. MCP-1 and MIP-1ß expression was also found altered in DMH and regulated by the drugs. Anti-angiogenic role of piroxicam and C-phycocyanin is well demonstrated.

Piroxicam and c-phycocyanin prevent colon carcinogenesis by inhibition of membrane fluidity and canonical Wnt/ß-catenin signaling while up-regulating ligand dependent transcription factor PPARγ.

The colon cancer tissues from DMH treated rats exhibited higher membrane potential, fluidity and changed lipid order as examined by Merocyanine 540 and 1,6-diphenyl-1,3,5-hexatriene, respectively. A transition from gel to liquid crystalline state was observed by Laurdan fluorescence and also reduced fluorescence quenching of NBD-PE as contributed in the decreased membrane lipid phase separation. With piroxicam, a traditional NSAID and c-phycocyanin, a biliprotein from Spirulina platensis, these effects were normalized. An augmented intracellular Ca(+2) had contributed to the drug mediated apoptosis which is supported by an elevated calpain-9 expression. Histopathologically, a large pool of secreted acid/neutral mucopolysaccrides as well as the presence of blood vessels and dysplastic crypts signifies invasive mucinous adenocarcinoma while both the drugs reduced these neoplastic alterations. Wnt/ß-catenin pathway was also found to be up-regulated which served as a crucial indicator for cancer cell growth. A concomitant down regulation of PPARγ was noted in DMH treatment which is associated with tumor progression. The expression of PPARα and δ, the other two isoforms of PPAR family was also modulated. We conclude that piroxicam and c-phycocyanin exert their anti-neoplastic effects via regulating membrane properties, raising calpain-9 and PPARγ expression while suppressing Wnt/ß-catenin signaling in experimental colon carcinogenesis.