A primary mode of cancer prevention and early detection in the United States is the widespread practice of screening. Although many strategies for early detection and prevention are available, ...adverse outcomes, such as overdiagnosis and overtreatment, are prevalent among those utilizing these approaches. Broad use of mammography and prostate cancer screening are key examples illustrating the potential harms stemming from the detection of indolent lesions and the subsequent overtreatment. Furthermore, there are several cancers for which prevention strategies do not currently exist. Clinical and experimental evidence have expanded our understanding of cancer initiation and progression, and have instructed the development of improved, precise modes of cancer prevention and early detection. Recent cancer prevention and early detection innovations have begun moving towards the integration of molecular knowledge and risk stratification profiles to allow for a more accurate representation of at-risk individuals. The future of cancer prevention and early detection efforts should emphasize the incorporation of precision cancer prevention integration where screening and cancer prevention regimens can be matched to one's risk of cancer due to known genomic and environmental factors.
Background. Colorectal cancer (CRC) incidence and mortality has been declining in the U.S. Despite success in reducing CRC incidence, incidence of early-onset CRC has increased markedly. In this ...study, we identified age-related disparities in CRC incidence and mortality, and investigated differences in anatomical distribution of colon cancers between populations. Methods. CRC trends were evaluated using Surveillance, Epidemiology, and End Results Program Data from 1980–2016 for individuals under age 50 and 50 years and older. Rates and ratios were calculated using SEER∗Stat. Regression analyses were calculated using Joinpoint. Results. Increased CRC incidence among individuals under age 50 was observed. Among individuals under age 50, incidence-based mortality (IBM) stabilized, while incidence and IBM decreased for individuals aged 50 years and older. Normalized trends indicated increased rectal cancer incidence for individuals under age 50, particularly among individuals aged 30–39. Similar incidence of proximal and distal colon cancers in individuals under age 50 was observed, while colon cancers in individuals aged 50 and older were primarily distal. Conclusions. We found age-related disparities in CRC incidence and IBM between individuals under age 50 and age 50 years and older. Increasing incidence rates of rectal cancer substantially accounts for this disparity among individuals under age 50. The escalating trends of early-onset CRC warrant investigation into the factors leading to the population-level trends.
PurposeCarpal tunnel syndrome (CTS) is a hand disease caused by the pressing of the median nerve present in the palmar side of the wrist. It causes severe pain in the wrist, triggering disturbance ...during sleep. Different products like splints, braces and gloves are available in the market to alleviate this disease but there was still a need to improve the wearability, comfort and cost of the product. This study was about designing a comfortable and cost-effective wearable system for mild-to-moderate CTS. Transcutaneous electrical nerve stimulation (TENS) therapy has been used to reduce the pain in the wrist.Design/methodology/approachAfter simulation by using Proteus software (which allowed the researchers to draw and simulate electrical circuits using ISIS, ARES and PCB design tools virtually), the circuit with optimum frequency, i.e. 33 Hz was selected, and the circuit was developed on a printed circuit board (PCB). The developed circuit was integrated successfully into the half glove structure.FindingsThe developed product had good thermophysiological comfort and hand properties as compared to the commercially available product of the same kind. In vivo testing (It involves the testing with living subjects like animals, plants or human beings) was performed which resulted in 85% confirmed viability of the product against CTS. A glove with an integrated circuit was developed successfully to accommodate various sizes without any sex specifications in a cost-effective way to mitigate the issue of CTS.Research limitations/implicationsIndustrial workers, individuals frequently using their hands or those diagnosed with CTS may wish to use this product as therapy. The attention could not be paid to the aesthetic or visual appeal of the developed product.Originality/valueA very comfortable glove with integrated TENS electrodes was developed successfully to accommodate various sizes without any sex specifications in a cost-effective way to mitigate the issues of CTS.
There exists no coherent national strategy for the early detection or prevention of gastric cancer in the United States (US), even among identified high-risk groups such as Asian Americans, African ...Americans, Hispanic Americans, and Alaska Native/American Indian peoples. As a result, patients with gastric cancer in the US are diagnosed at later stages and demonstrate worse overall survival compared to nations of East Asia with established screening programs (
Table 1
). The under-recognition of gastric cancer risk within minority communities is a significant unaddressed healthcare disparity.
To address this disparity, the Division of Gastroenterology and Hepatology and the Center for Asian Health Research and Education at Stanford University hosted the inaugural Gastric Cancer Summit on March 5–6, 2020. This Summit brought together academic physicians, researchers, policy leaders, and patient advocates to identify strategies to combat gastric cancer in high-risk US populations through prevention and early detection. The first day of the Summit consisted of health policy- and advocacy-oriented presentations, and the second day consisted of scientific presentations on advances in early detection and prevention.
Firstly I would like to appreciate the views and compliments. I was mentioning to Mr Idrees Khawaja that perhaps they could have chosen a much better representative for the private sector because my ...view is distinctly in the minority in case of RGST. I will just share with you where the private sector stands on the issue of RGST, what their opinion is and then I will give you my own stance on the subject as well as justification on the same. As you would know from newspapers and other media, the private sector is strongly against the imposition of RGST. The vast majority of chambers, which represent the bulk of Pakistan’s private sector, have been vociferous in the opposition of RGST. I must mention here that in addition to my responsibilities at Engro, I also serve in the role of Chairman of Pakistan Business Council, which was created a few years ago. Pakistan Business Council comprises of largest business groups of Pakistan. Every single large business group of Pakistan is its member, including some of the key multinationals operating in Pakistan. Pakistan Business Council formally supported the RGST, even during its hearing in the National Assembly Finance Committee. Part of the difference that you see here can be explained in terms which would be flattering to us. We have been part of the industry since a very long time but we realise where the world is headed, and understand that a modern country cannot progress and cannot be run effectively with a tax-to-GDP ratio which is in single digit. But since the private sector is not significantly represented here, I think it is only fair that I try to bring forth where some of their apprehensions come from. We at large businesses have management systems and teams who are sophisticated enough to deal with complex systems. We have the necessary resources which enable us to engage the most expensive lawyers in Pakistan, and fight with the FBR when we see corruption or unfair practices being carried out. We can also raise issues that we face in front of the highest authority in the country. The vast majority of the Pakistani businessmen are small traders or small manufacturers. They do not have the systems and resources like large companies. Moreover, fact of the matter is that the tax machinery in Pakistan is both incompetent and corrupt. Therefore, it is a very legitimate concern on part of the business community that the RGST will make their lives difficult, more than the way economic theory portrays it to be. This is because there are certain realities that have to be looked at.
Recent clinical trial data from Lynch Syndrome (LS) carriers demonstrated that naproxen administered for 6-months is a safe primary chemoprevention that promotes activation of different resident ...immune cell types without increasing lymphoid cellularity. While intriguing, the precise immune cell types enriched by naproxen remained unanswered. Here, we have utilized cutting-edge technology to elucidate the immune cell types activated by naproxen in mucosal tissue of LS patients.
Normal colorectal mucosa samples (pre- and post-treatment) from a subset of patients enrolled in the randomized and placebo-controlled 'Naproxen Study' were obtained and subjected to a tissue microarray for image mass cytometry (IMC) analysis. IMC data was processed using tissue segmentation and functional markers to ascertain cell type abundance. Computational outputs were then used to quantitatively compare immune cell abundance in pre- and post-naproxen specimens.
Using data-driven exploration, unsupervised clustering identified four populations of immune cell types with statistically significant changes between treatment and control groups. These four populations collectively describe a unique cell population of proliferating lymphocytes within mucosal samples from LS patients exposed to naproxen.
Our findings show that daily exposure of naproxen promotes T-cell proliferation in the colonic mucosa, which paves way for developing combination of immunoprevention strategies including naproxen for LS patients.
Effective approaches for prevention of hepatocellular carcinoma (HCC) will have a significant impact on HCC-related mortality. There are strong preclinical data and rationale to support targeting ...epidermal growth factor receptor (EGFR) for HCC chemoprevention. Small molecule inhibitors of EGFR have been Food and Drug Administration–approved for cancer therapy, which provides an opportunity to repurpose one of these drugs for chemoprevention of HCC. Unfortunately, the frequency of side effects associated with administration of these drugs at oncology doses renders them ineffective for chemoprevention. This clinical trial assesses whether lower doses of one of these inhibitors, erlotinib, still engages EGFR in the liver to block signaling (eg, EGFR phosphorylation). The objective of this clinical trial was determination of a safe and minimum effective dose of erlorinib for which ≥ 50% reduction phospho-EGFR immunohistochemical staining in the liver was observed.
Forty six participants were preregistered and 25 participants were registered in this multicenter trial. By dose de-escalation trial design, cohorts of participants received a 7-day course of erlotinib 75 mg/day, 50 mg/day or 25 mg/day with liver tissue acquisition prior to and after erlotinib.
A ≥50% reduction phospho-EGFR immunohistochemical staining in the liver was observed in a minimum of 40% of participants (predetermined threshhold) at each of the dose levels. Erlotinib was very well tolerated with few side effects observed, particularly at the dose of 25 mg/day. Favorable modulation of the Prognostic Liver Signature was observed in participants who received erlotinib.
These data support the selection of erlotinib doses as low as 25 mg/day of for a longer intervention to assess for evidence of efficacy as an HCC chemoprevention drug (ClinicalTrials.govNCT02273362).
Cancer immunoprevention refers to the modulation of the host immune response to control the initiation or development of cancer. The significant role of host immunity in early tumorigenesis has only ...recently been confirmed, as a better understanding of the mechanisms, molecules and cells involved in tumor immunology have been elucidated over the past two decades. Of utmost importance, preclinical and clinical evidences have demonstrated that early neoplastic cells (transformed cells that initiate cancer formation) express antigens that allow the immune system to distinguish them from normal cells. Furthermore, recognition of the aberrant cell by the immune cells activates a complex interaction of mutual modulation between the immune cells, the tumor and the tumor microenvironment that may result not only in inhibition but also promotion of cancer. The deepening understanding of cancer-related immunologic processes, properties, and components has spawned exploration of more rational, mechanism-based immunologic strategies (using vaccines, antibodies, and immune modulators) for cancer prevention. This introduction to the Cancer Prevention Research immunoprevention series will attempt to review the basics of the immune response modulation as a basis for potential application to cancer immunoprevention strategies with an emphasis on vaccines. Recognizing the fast-paced research in immune response modulation, the series will cover current understandings and future directions of cancer immunoprevention research.
BackgroundMicrosatellite instability (MSI) tumors are characterized by defects in the DNA mismatch repair (MMR) genes that lead to the accumulation of mutations within microsatellite (MS) loci. ...Indels in MS regions of coding genes can result in the synthesis of shared frameshift peptide (FSP) neoantigens, expected to be immunogenic and safe. MSI tumors develop sporadically or secondary to hereditary predisposition as part of Lynch Syndrome (LS), one of the most common hereditary colorectal cancers. Nous-209 is a genetic vaccine encoding 209 neoantigens shared across sporadic and hereditary MSI tumors developed for interception and treatment of MSI tumors.1 A phase I trial (NCT04041310) combining the Nous-209 vaccine with pembrolizumab anti-PD-1 antibody has been recently completed in metastatic colorectal, gastric and gastro-esophageal cancer patients showing excellent safety, immunogenicity, and promising signs of clinical efficacy.2 3 Here, we report the safety and immunogenicity of Nous-209 from the Phase Ib/II trial in LS carriers for the first 10 subjects.MethodsNCT05078866 is a Phase Ib/II single-arm, open-label, clinical trial testing Nous-209 monotherapy for immune-interception in LS carriers. Safety and immunogenicity are the co-primary objectives. Nous-209 is administered intramuscularly: one prime with a Great Ape Adenovirus (GAd20-209-FSPs) on day 1, and boost with a Modified Vaccinia Ankara (MVA-209-FSPs) at week 8. Blood samples are collected for biomarker assays (Baseline, weeks 3, 8, 9, 24, and 52). Immunogenicity is evaluated on PBMC before and after vaccination by ex-vivo IFNγ ELISpot assay.ResultsOn the data cutoff date (28 May 2023), 21 patients were enrolled in this NCI-sponsored study, 18 of those treated with both GAd and MVA. No dose limiting serious adverse events (SAEs) were observed (n=10), and the treatment appears safe and well tolerated. Immunogenicity was demonstrated in 100% of tested patients (n=10) with a mean peak response of ~700 IFN-γ SFCs/million PBMCs. No immune responses were detected at baseline prior vaccination in either previvors or survivors LS carriers. Nous-209-induced T cell responses were broad, recognizing different FSPs with induction of both CD4 and CD8 T cell responses. Deconvolution of T cell responses against predicted CD8 epitopes included in the FSPs pools showed multiple positive responses, confirming the optimal breadth of immune responses.ConclusionsNous-209 is safe, well tolerated, and elicits potent and broad immune response in both LS carriers previvors and survivors, supporting Nous-209 development as a compelling approach for LS cancer interception.ReferencesLeoni G, et al. A genetic vaccine encoding shared cancer neoantigens to treat tumors with microsatellite instability. Cancer Res. 2020;80(18):3972–3982.Fakih M, et al. First clinical and immunogenicity results including all subjects enrolled in a phase I study of Nous-209, an off-the-shelf immunotherapy, with pembrolizumab, for the treatment of tumors with a deficiency in mismatch repair/microsatellite instability (dMMR/MSI). Journal of Clinical Oncology 2022;40(16_suppl):2515–2515.D’Alise AM, et al. Adenoviral-based vaccine promotes neoantigen-specific CD8+ T cell stemness and tumor rejection. Science Translational Medicine 2022;14(657):eabo7604.
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