Analysis of molecular aberrations of Wnt pathway gladiators in colorectal cancer in the Kashmiri population

<p>Abstract</p> <p>The development and progression of colorectal cancer (CRC) is a multi-step process, and the Wnt pathways with its two molecular gladiators adenomatous polyposis coli (<it>APC</it>) and <it>β-catenin </it>plays an important role in transforming a normal tissue into a malignant one. In this study, we aimed to investigate the role of aberrations in the <it>APC </it>and <it>β-catenin </it>genes in the pathogenesis of CRC in the Kashmir valley, and to correlate it with various clinicopathological variables. We examined the paired tumour and normal-tissue specimens of 86 CRC patients for the occurrence of aberrations in the mutation cluster region (MCR) of the <it>APC </it>gene and exon 3 of the β-<it>catenin </it>gene by polymerase chain reaction-single-strand conformation polymorphism (PCR-SSCP) and/or PCR-direct sequencing. Analysis of promoter hypermethylation of the <it>APC </it>gene was also carried out using methylation-specific PCR (MS-PCR). The overall mutation rate of the MCR of the APC gene among 86 CRC cases was 12.8 per cent (11 of 86). Promoter hypermethylation of <it>APC </it>was observed in 54.65 per cent (47 of 86) of cases. Furthermore, we found a significant association between tumour location, tumour grade and node status and the methylation status of the <it>APC </it>gene (<it>p </it>≤ 0.05). Although the number of mutations in the <it>APC </it>and <it>β-catenin </it>genes in our CRC cases was very low, the study confirms the role of epigenetic gene silencing of the pivotal molecular gladiator, <it>APC</it>, of the Wnt pathway in the development of CRC in the Kashmiri population.</p

Enabling Solution Processible COFs through Suppression of Precipitation during Solvothermal Synthesis

Covalent organic frameworks (COFs) are crystalline, nanoporous materials of interest for various applications. However, current COF synthetic routes lead to insoluble aggregates which hamper processing and prohibit their use in many applications. Here, we report a novel COF synthesis method that produces a stable, homogeneous suspension of crystalline COF nanoparticles. Our approach involves the use of a polar solvent, di-acid catalyst, and slow reagent mixing procedure at elevated temperatures which all together enable access to crystalline COF nanoparticle suspension that does not aggregate or precipitate when kept at elevated temperatures. On cooling, the suspension undergoes a thermoreversible gelation transition to produce crystalline and highly porous COF materials. We demonstrate that this method enables the preparation of COF monoliths, membranes, and films using conventional solution processing techniques. We show that the modified synthesis approach is compatible with various COF chemistries, including both large- and small-pore imine COFs, hydrazone-linked COFs, and COFs with rhombic and hexagonal topology, and in each case, we demonstrate that the final product has excellent crystallinity and porosity. The final materials contain both micro- and macropores, and the total porosity can be tuned through variation of sample annealing. Dynamic light scattering measurements reveal the presence of COF nanoparticles that grow with time at room temperature, transitioning from a homogeneous suspension to a gel. Finally, we prepare imine COF membranes and measure their rejection of polyethylene glycol (PEG) polymers and oligomers, and these measurements exhibit size-dependent rejection of PEG solutes. This work demonstrates a versatile processing strategy to create crystalline and porous COF materials using solution processing techniques and will greatly advance the development of COFs for various applications

Mutational spectrum of conserved regions of TP53 and PTEN genes in Kangri cancer (of the skin) in the Kashmiri population

Kangri cancer is a unique, thermally induced squamous cell carcinoma (SCC) of the skin that develops due to persistent use of a Kangri (a brazier) by the Kashmiri people to combat the cold temperature during winter. Unlike classical UV-induced SCC of the skin, Kangri cancer appears on the legs and abdomen. Its common features are erythematous patches, recurrence and metastasis. In the absence of any molecular etiology, we made a preliminary attempt to estimate the nature and frequency of mutations in the TP53 and PTEN genes in Kangri cancer patients from Kashmir. PCR-SSCP analysis followed by direct sequencing revealed that TP53 mutations account for 40% (12/30) of sporadic Kangri cancer patients and that PTEN mutations account for only 6.6% (2/30). There were 16 mutations in TP53 exons 5 and 7, found in 12 patients. They consisted of 11 substitutions (7 transitions, 3 transversions and 1 double-base) and 5 insertions. The 11 substitutions represent 8 distinct missense mutations, 3 of which were silent mutations. The mutations detected in the PTEN gene consisted of one insertion and one C > T transition. This high percentage of TP53 mutations (especially A > G) showed a statistically significant association with age and positive lymph node status. Our results indicate that TP53 is a predominant target of chronic hyperthermia in the development of Kangri cancer in the moderate risk Kashmiri population. The differences in the TP53 mutation spectrum of UV-induced SCC of the skin and Kangri cancer are probably due to the nature of the respective environmental carcinogens. The study also suggests that TP53 may function as a potential molecular marker and prognostic tool, at least in a subset of sporadic Kangri tumors

Gastric Cancer in Young Patients

Aim. The aim of this study was to see the clinical, pathological, and demographic profile of young patients with stomach carcinoma besides association with p53. Patients and Methods. Prospective study of young patients with stomach carcinoma from January 2005 to December 2009. A total of 50 patients with age less than 40 years were studied. Results. Male female ratio was 1 : 1.08 in young patients and 2.5 : 1 in older patients. A positive family history of stomach cancer in the first degree relatives was present in 10% of young patients. Resection was possible only in 50% young patients. 26% young patients underwent only palliative gastrojejunostomy. The most common operation was lower partial gastrectomy in 68%. Amongst the intraoperative findings peritoneal metastasis was seen in 17.4% in young patients. 50% young patients presented in stage IV as per AJCC classification (P value .004; sig.). None of the patients presented as stage 1 disease in young group. Conclusion. Early detection of stomach carcinoma is very important in all patients but in young patients it is of paramount importance

Aberrant promoter methylation and reduced expression of p16 gene in esophageal squamous cell carcinoma from Kashmir valley: a high-risk area

Esophageal squamous cell carcinoma (ESCC) is one of the most prevalent cancer in Jammu and Kashmir region of India and has multi-factorial etiology involving dietary habits, genetic factors, and gene environmental interactions. Inactivation of the p16 gene expression by aberrant promoter methylation plays an important role in the progression of esophageal carcinoma. In the present investigation, we have studied the role of p16 promoter methylation in 69 histopathologically confirmed ESCC tissues and compared it with corresponding normal adjacent tissues for DNA methylation in the CpG island in the p16 promoter region by methylation-specific polymerase chain reaction (MSP) and p16 protein expression by immunoblotting. The results showed loss of p16 expression in 67% (46/69) of tumor tissues compared to only 3% in control tissues (2/69). Promoter methylation was observed in 52% (36/69) of tumor tissues and it gradually increased with the increasing severity of histological grades of the cancer (P = 0.0001). Loss of p16 expression with promoter methylation was observed in 26 of 36 cases (72%). Analysis of patients dietary habits revealed a strong association between promoter methylation and high consumption of hot salted tea (P &#60; 0.05) which is a most favourite drink commonly consumed by Kashmiri people

A multinational cross-sectional study on the awareness and concerns of healthcare providers toward monkeypox and the promotion of the monkeypox vaccination

BackgroundThe aim of this study was to explore potential healthcare workers' (HCWs) concerns about the monkeypox virus in order to create practical solutions to manage this disease.MethodsOnline cross-sectional research was conducted in 11 Arabic countries (Egypt, Saudi Arabia, Yemen, Syria, Libya, Algeria, Tunisia, Iraq, Palestine, Jordan, and Sudan) from 2 August 2022 to 28 December 2022.ResultsApproximately 82% of respondents felt the need to acquire further information. The acceptability of the vaccine against monkeypox has been indicated by more than half of the participants (54.5%). Furthermore, we state that 45% of the participants are knowledgeable about the monkeypox virus, and 53.1% of the participants have never been affected with COVID-19 before are more worried about COVID-19 than about monkeypox. Participants diagnosed with COVID-19 were 0.63 times less likely to worry about monkeypox than those who were not diagnosed with COVID-19. A greater willingness to get the monkeypox vaccination was seen among the age group 21–30 years (42.4%) compared to the other age groups.ConclusionMost healthcare professionals have a moderate knowledge of the monkeypox virus. Furthermore, they demonstrated a low willingness to get the vaccination against the monkeypox virus