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rjzimmerman · 3 months ago

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Excerpt from this story from Down East Magazine:

Joseph Monninger passed away on January 1, 2025, at age 71, a few weeks after this issue went to press. Monninger authored more than two dozen novels and other books, including a 2023 memoir, Goodbye to Clocks Ticking: How We Live While Dying. He taught writing at Plymouth State University for 32 years. After his cancer diagnosis, in 2021, he settled year-round in Pembroke.

Abald eagle visits me every day. I have learned to recognize his voice as he approaches, a querulous complaint against the crows that usually accompany him like a desperate ring of courtiers vying for his attention. To people who will listen, I have mentioned that to be an eagle is to be harassed from sunup to sundown. If the crows leave him alone for a moment, their place is taken by herring gulls cursing his existence. No one likes an eagle except other eagles, it seems, and the eagle shrinks down when the birds dive at him, this bandit among the large pines. Half amused, half ashamed of his bulk and thieving nature, he settles on the topmost rim of branches, a Billy Budd foretopman, his eyes scanning the cold waters of the Pennamaquan River as it merges with Cobscook Bay.

I count on his visits and keep two sets of binoculars nearby, wanting to have a pair within reach wherever I happen to be on my two acres of land in Pembroke, a small community that once took its living from the sea. I am aware that the eagle has become something of a project for me. My son, when he calls from his home in New Hampshire, asks if I have seen the eagle that day, and I know that he is asking out of kindness, out of an acknowledgement of my age and the emptiness of my daily calendar, and yet I can’t help playing my part and relating to him the itinerary of the eagle’s visit. Yes, I tell him, the eagle came early this morning, stayed for nearly 15 minutes, and yes, it was on that perch on The Eagle Tree, the name I have for the bird’s favorite pine. Last year, a storm took down the tallest pine overlooking the water, and I worried that the eagle would find another place to rest while the crows and gulls hectored him. But the eagle has taken to the new tree, and so it is a safe, light topic that my son and I can explore without any of the weightier subjects that circle around us. We both know that this beautiful land overlooking this vibrant estuary is the place I am making my last stand. I live here with stage-four lung cancer, each motion, however minimal, underlined by a dry cough, my fist to my lips, my heart and head and breath paused for a moment while I wonder if and how I will continue.

So the eagle is useful and welcome. It is understood now that I am becoming mist, the ghost of my youthful life, an old man who swims in the sea and rivers to bathe, a rough birch cane in my left hand to steady myself and sometimes to help me stand. I have chosen to live this way, to live near the sea without running water, to surround myself with simple beauty. My days have been emptied of all fanfare and complication. I play chess on the computer, read great gulps of books, nap, and study the weather both in the sky and in my chest. I watch the Red Sox replay in the early morning, at first light, and find I have not given up rooting for our beloved nine. I was an Orioles fan as a boy, but 40 years in New England has changed my loyalty. The players, however, are becoming mist as well. My childhood hero, Brooks Robinson, died this past year, but I see him in the young Sox players, see myself, honestly, standing at the plate, the smell and taste of dirt and chalk and a dense wool uniform heated by the sun. Those memories are here too.

#Joseph Monninger

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bbmct · 6 months ago

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BBMCT: Set Up New Medical Research at AIIMS Hospital

British Biomedicine Clinical Trials (BBMCT) has become a pivotal player in advancing clinical research at prestigious medical institutions like the All India Institute of Medical Sciences (AIIMS) Hospital. As the medical field continues to evolve, collaboration with global leaders in clinical trials plays an essential role in driving progress. BBMCT, through its expert partnerships, has been instrumental in setting up new medical research at AIIMS Hospital, enriching patient care, accelerating innovation, and fostering collaborations that enhance the future of healthcare.

In this blog post, we will delve into the multiple ways in which BBMCT contributes to AIIMS Hospital’s research, its impact on patient care, and the broader medical community. The following subheadings will explore how BBMCT facilitates advancements in medical research at AIIMS and beyond.

## Enhances Patient Care and Outcomes

BBMCT plays a crucial role in improving patient care and outcomes by facilitating clinical trials that bring new treatments and therapies to the forefront. These trials not only help test the safety and efficacy of medical interventions but also give patients access to cutting-edge therapies that are not yet widely available. By setting up new clinical research initiatives at AIIMS Hospital, BBMCT ensures that patients receive the best possible care while contributing to the global understanding of disease management.

Furthermore, the data generated from clinical trials at AIIMS aids in creating tailored treatment plans for patients, improving long-term health outcomes. This personalized approach enhances the hospital’s capacity to treat complex conditions, such as cancer, cardiovascular diseases, and autoimmune disorders.

## Accelerates the Progress of Innovations

BBMCT has been instrumental in accelerating the progress of medical innovations at AIIMS Hospital. Through well-structured clinical trials, BBMCT supports the testing of novel drugs, medical devices, and treatment protocols. This fast-tracks the transition of groundbreaking innovations from laboratory research to real-world applications, benefiting patients and healthcare professionals alike.

Innovations in personalized medicine, gene therapy, and immunotherapy are among the key areas that BBMCT fosters at AIIMS. By supporting these cutting-edge studies, BBMCT plays a pivotal role in reshaping the future of healthcare by bringing innovative solutions to the clinical setting faster than traditional research timelines would allow.

## Establishes Partnerships with Leading Institutions

One of BBMCT’s core strengths is its ability to form strategic partnerships with leading medical institutions globally. This enables AIIMS Hospital to collaborate with renowned experts and access state-of-the-art research tools and resources. By creating these collaborative networks, BBMCT ensures that research conducted at AIIMS benefits from the latest global insights and methodologies.

These partnerships are essential in setting up new medical research projects, particularly in areas that require specialized expertise. Moreover, they help strengthen AIIMS’s position as a hub for advanced medical research in India, ensuring that the hospital remains at the forefront of global healthcare developments.

## Fills Significant Gaps in Knowledge

A major benefit of BBMCT’s involvement in clinical trials is its ability to fill critical gaps in medical knowledge. Despite significant advances in medicine, many diseases still lack effective treatments, and there are numerous unexplored areas in patient care. By facilitating clinical research at AIIMS Hospital, BBMCT provides a platform for addressing these gaps.

Research conducted through BBMCT often focuses on rare diseases, emerging health threats, and under-researched conditions, where traditional research may fall short. This focus allows AIIMS to contribute valuable insights into both common and niche medical conditions, benefiting not only Indian patients but the global population.

## Secures Funding for Research Projects

Conducting world-class clinical research requires substantial funding. BBMCT’s involvement at AIIMS Hospital significantly enhances the institution’s ability to secure grants and funding for critical medical research projects. The collaboration between BBMCT and AIIMS Hospital has attracted international funding from government agencies, private organizations, and philanthropic entities, ensuring that research can be carried out without financial constraints.

This funding also enables AIIMS to invest in state-of-the-art equipment, recruit top-tier researchers, and scale up promising research initiatives. The financial support secured by BBMCT ensures that AIIMS remains a leader in cutting-edge healthcare research in India.

## Improves the Institution’s Academic Reputation

AIIMS Hospital is renowned for its academic excellence, and BBMCT’s partnership further enhances its reputation as a leading institution in clinical research. By conducting high-quality clinical trials in collaboration with BBMCT, AIIMS attracts international attention, allowing it to recruit world-class researchers and practitioners to its team.

Furthermore, the findings from clinical trials conducted at AIIMS contribute to scientific literature, enhancing the institution’s academic standing. As a result, AIIMS becomes a sought-after partner for other research organizations and institutions looking to collaborate on innovative medical studies.

## Promotes Collaboration Among Research Teams

BBMCT’s involvement in clinical trials fosters a culture of collaboration among researchers, healthcare professionals, and experts from various fields. AIIMS Hospital, with its multidisciplinary approach to healthcare, greatly benefits from this collaboration. Researchers working on clinical trials, pharmaceutical companies, healthcare providers, and other stakeholders come together to achieve shared goals, ultimately advancing the field of medicine.

Collaboration also promotes knowledge exchange and the sharing of resources, making it easier to tackle complex medical problems. This networked approach accelerates the pace of discovery, ensuring that treatments and therapies are developed more efficiently.

## Supports Advancements Based on Evidence

BBMCT ensures that all clinical trials at AIIMS Hospital are rooted in evidence-based research. By relying on scientifically sound methodologies, the trials conducted through this collaboration lead to reliable and valid results that can be generalized to larger patient populations. This evidence-based approach is crucial in ensuring that any new treatment or therapy tested at AIIMS is not only safe but also effective.

Furthermore, this reliance on evidence supports informed decision-making in the medical field, providing healthcare providers with the information they need to offer the best care to their patients. It also plays a role in shaping public health policies based on proven data.

/media/fe48b75114c4a7ccf24b7775c9477286

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### FAQs About BBMCT and Its Role at AIIMS Hospital

**1. What is BBMCT’s role at AIIMS Hospital?**

BBMCT (British Biomedicine Clinical Trials) plays a crucial role in facilitating advanced clinical research at AIIMS Hospital by organizing and supporting clinical trials. These trials test new drugs, medical devices, and treatment protocols, enhancing patient care, improving health outcomes, and accelerating medical innovations. Through BBMCT’s partnership, AIIMS benefits from expertise, global collaborations, and increased funding for research.

**2. How does BBMCT improve patient outcomes?**

BBMCT improves patient outcomes by providing access to cutting-edge treatments that are still in clinical trial phases. Patients participating in these trials receive advanced medical care that might not be available through traditional treatment routes. The trials help test new therapies that can ultimately lead to better, more effective treatments for various diseases, improving long-term health outcomes.

**3. What innovations does BBMCT support at AIIMS?**

BBMCT supports a variety of innovative medical treatments at AIIMS, including advancements in gene therapy, immunotherapy, and personalized medicine. Through its clinical trials, BBMCT accelerates the development of new drugs, medical devices, and technologies, contributing to the advancement of healthcare solutions that address complex medical conditions such as cancer, cardiovascular diseases, and chronic illnesses.

**4. How does BBMCT help AIIMS secure research funding?**

BBMCT plays an essential role in helping AIIMS secure funding by attracting grants and sponsorships from government agencies, private foundations, and international research organizations. These funds are crucial for supporting the infrastructure and operations of clinical trials, ensuring that AIIMS remains equipped to conduct high-quality research that leads to breakthrough medical discoveries.

**5. How do BBMCT’s partnerships benefit AIIMS Hospital?**

BBMCT’s partnerships with leading medical institutions and research organizations enhance AIIMS’s ability to access cutting-edge research techniques, resources, and global expertise. These collaborations foster knowledge exchange, expand research opportunities, and improve the overall quality of research at AIIMS, helping the institution stay at the forefront of medical advancements.

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### Conclusion

British Biomedicine Clinical Trials (BBMCT) has been instrumental in advancing clinical research at AIIMS Hospital, contributing to improved patient care, faster medical innovations, and a stronger academic reputation for the institution. Through strategic partnerships, evidence-based research, and enhanced funding opportunities, BBMCT has positioned AIIMS as a leader in healthcare research. The collaborative spirit fostered by BBMCT ensures that AIIMS continues to make significant contributions to medical science, ultimately benefiting both Indian and global populations. With the continued support of BBMCT, AIIMS Hospital is poised to lead the way in groundbreaking medical research and patient care for years to come.

Subscribe to BBMCLINICALTRIALS YouTube channel for Research Insights

Be sure to subscribe to the **BBMCLINICALTRIALS YouTube channel** for exclusive access to the latest updates and in-depth insights into British Biomedicine Clinical Trials (BBMCT). Stay informed on cutting-edge research, clinical trial advancements, patient safety protocols, and breakthrough therapies being tested at AIIMS Hospital. Our channel provides expert discussions, industry trends, and detailed videos on the clinical trial process across various therapeutic areas. Whether you’re a healthcare professional, researcher, or simply interested in biomedical innovation, subscribing will keep you at the forefront of clinical research developments. Don’t miss out — join our community today!

#anya mouthwashing #artists on tumblr #agatha harkness #bucktommy #batman #cats of tumblr #captain curly #agatha all along #911 abc

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myrawjcsmicasereports · 7 months ago

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Inhibition of EIF4E Downregulates VEGFA and CCND1 Expression to Suppress Ovarian Cancer Tumor Progression by Jing Wang in Journal of Clinical Case Reports Medical Images and Health Sciences

Abstract

This study investigates the role of EIF4E in ovarian cancer and its influence on the expression of VEGFA and CCND1. Differential expression analysis of VEGFA, CCND1, and EIF4E was conducted using SKOV3 cells in ovarian cancer patients and controls. Correlations between EIF4E and VEGFA/CCND1 were assessed, and three-dimensional cell culture experiments were performed. Comparisons of EIF4E, VEGFA, and CCND1 mRNA and protein expression between the EIF4E inhibitor 4EGI-1-treated group and controls were carried out through RT-PCR and Western blot. Our findings demonstrate elevated expression of EIF4E, VEGFA, and CCND1 in ovarian cancer patients, with positive correlations. The inhibition of EIF4E by 4EGI-1 led to decreased SKOV3 cell clustering and reduced mRNA and protein levels of VEGFA and CCND1. These results suggest that EIF4E plays a crucial role in ovarian cancer and its inhibition may modulate VEGFA and CCND1 expression, underscoring EIF4E as a potential therapeutic target for ovarian cancer treatment.

Keywords: Ovarian cancer; Eukaryotic translation initiation factor 4E; Vascular endothelial growth factor A; Cyclin D1

Introduction

Ovarian cancer ranks high among gynecological malignancies in terms of mortality, necessitating innovative therapeutic strategies [1]. Vascular endothelial growth factor (VEGF) plays a pivotal role in angiogenesis, influencing endothelial cell proliferation, migration, vascular permeability, and apoptosis regulation [2, 3]. While anti-VEGF therapies are prominent in malignancy treatment [4], the significance of cyclin D1 (CCND1) amplification in cancers, including ovarian, cannot be overlooked, as it disrupts the cell cycle, fostering tumorigenesis [5, 6]. Eukaryotic translation initiation factor 4E (EIF4E), central to translation initiation, correlates with poor prognoses in various cancers due to its dysregulated expression and activation, particularly in driving translation of growth-promoting genes like VEGF [7, 8]. Remarkably, elevated EIF4E protein levels have been observed in ovarian cancer tissue, suggesting a potential role in enhancing CCND1 translation, thereby facilitating cell cycle progression and proliferation [9]. Hence, a novel conjecture emerges: by modulating EIF4E expression, a dual impact on VEGF and CCND1 expression might be achieved. This approach introduces an innovative perspective to impede the onset and progression of ovarian cancer, distinct from existing literature, and potentially offering a unique therapeutic avenue.

Materials and Methods

Cell Culture

Human ovarian serous carcinoma cell line SKOV3 (obtained from the Cell Resource Center, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences) was cultured in DMEM medium containing 10% fetal bovine serum. Cells were maintained at 37°C with 5% CO2 in a cell culture incubator and subcultured every 2-3 days.

Three-Dimensional Spheroid Culture

SKOV3 cells were prepared as single-cell suspensions and adjusted to a concentration of 5×10^5 cells/mL. A volume of 0.5 mL of single-cell suspension was added to Corning Ultra-Low Attachment 24-well microplates and cultured at 37°C with 5% CO2 for 24 hours. Subsequently, 0.5 mL of culture medium or 0.5 mL of EIF4E inhibitor 4EGI-1 (Selleck, 40 μM) was added. After 48 hours, images were captured randomly from five different fields—upper, lower, left, right, and center—using an inverted phase-contrast microscope. The experiment was repeated three times.

GEPIA Online Analysis

The GEPIA online analysis tool (http://gepia.cancer-pku.cn/index.html) was utilized to assess the expression of VEGFA, CCND1, and EIF4E in ovarian cancer tumor samples from TCGA and normal samples from GTEx. Additionally, Pearson correlation coefficient analysis was employed to determine the correlation between VEGF and CCND1 with EIF4E.

RT-PCR

RT-PCR was employed to assess the mRNA expression levels of EIF4E, VEGF, and CCND1 in treatment and control group samples. Total RNA was extracted using the RNA extraction kit from Vazyme, followed by reverse transcription to obtain cDNA using their reverse transcription kit. Amplification was carried out using SYBR qPCR Master Mix as per the recommended conditions from Vazyme. GAPDH was used as an internal reference, and the primer sequences for PCR are shown in Table 1.

Amplification was carried out under the following conditions: an initial denaturation step at 95°C for 60 seconds, followed by cycling conditions of denaturation at 95°C for 10 seconds, annealing at 60°C for 30 seconds, repeated for a total of 40 cycles. Melting curves were determined under the corresponding conditions. Each sample was subjected to triplicate experiments. The reference gene GAPDH was used for normalization. The relative expression levels of the target genes were calculated using the 2-ΔΔCt method.

Western Blot

Western Blot technique was employed to assess the protein expression levels of EIF4E, VEGF, and CCND1 in the treatment and control groups. Initially, cell samples collected using RIPA lysis buffer were lysed, and the total protein concentration was determined using the BCA assay kit (Shanghai Biyuntian Biotechnology, Product No.: P0012S). Based on the detected concentration, 20 μg of total protein was loaded per well. Electrophoresis was carried out using 5% stacking gel and 10% separating gel. Subsequently, the following primary antibodies were used for immune reactions: rabbit anti-human polyclonal antibody against phospho-EIF4E (Beijing Boao Sen Biotechnology, Product No.: bs-2446R, dilution 1:1000), mouse anti-human monoclonal antibody against EIF4E (Wuhan Sanying Biotechnology, Product No.: 66655-1-Ig, dilution 1:5000), mouse anti-human monoclonal antibody against VEGFA (Wuhan Sanying Biotechnology, Product No.: 66828-1-Ig, dilution 1:1000), mouse anti-human monoclonal antibody against CCND1 (Wuhan Sanying Biotechnology, Product No.: 60186-1-Ig, dilution 1:5000), and mouse anti-human monoclonal antibody against GAPDH (Shanghai Biyuntian Biotechnology, Product No.: AF0006, dilution 1:1000). Subsequently, secondary antibodies conjugated with horseradish peroxidase (Shanghai Biyuntian Biotechnology, Product No.: A0216, dilution 1:1000) were used for immune reactions. Finally, super-sensitive ECL chemiluminescence reagent (Shanghai Biyuntian Biotechnology, Product No.: P0018S) was employed for visualization, and the ChemiDocTM Imaging System (Bio-Rad Laboratories, USA) was used for image analysis.

Statistical Analysis

GraphPad software was used for statistical analysis. Data were presented as (x ± s) and analyzed using the t-test for quantitative data. Pearson correlation analysis was performed for assessing correlations. A significance level of P < 0.05 was considered statistically significant.

Results

3D Cell Culture of SKOV3 Cells and Inhibitory Effect of 4EGI-1 on Aggregation

In this experiment, SKOV3 cells were subjected to 3D cell culture, and the impact of the EIF4E inhibitor 4EGI-1 on ovarian cancer cell aggregation was investigated. As depicted in Figure 1, compared to the control group (Figure 1A), the diameter of the SKOV3 cell spheres significantly decreased in the treatment group (Figure 1B) when exposed to 4EGI-1 under identical culture conditions. This observation indicates that inhibiting EIF4E expression effectively suppresses tumor aggregation.

Expression and Correlation Analysis of VEGFA, CCND1, and EIF4E in Ovarian Cancer Samples

To investigate the expression of VEGFA, CCND1, and EIF4E in ovarian cancer, we utilized the GEPIA online analysis tool and employed the Pearson correlation analysis method to compare expression differences between tumor and normal groups. As depicted in Figures 2A-C, the results indicate significantly elevated expression levels of VEGFA, CCND1, and EIF4E in the tumor group compared to the normal control group. Notably, the expression differences of VEGFA and CCND1 were statistically significant (p < 0.05). Furthermore, the correlation analysis revealed a positive correlation between VEGFA and CCND1 with EIF4E (Figures 2D-E), and this correlation exhibited significant statistical differences (p < 0.001). These findings suggest a potential pivotal role of VEGFA, CCND1, and EIF4E in the initiation and progression of ovarian cancer, indicating the presence of intricate interrelationships among them.

EIF4E, VEGFA, and CCND1 mRNA Expression in SKOV3 Cells

To investigate the function of EIF4E in SKOV3 cells, we conducted RT-PCR experiments comparing EIF4E inhibition group with the control group. As illustrated in Figure 3, treatment with 4EGI-1 significantly reduced EIF4E expression (0.58±0.09 vs. control, p < 0.01). Concurrently, mRNA expression of VEGFA (0.76±0.15 vs. control, p < 0.05) and CCND1 (0.81±0.11 vs. control, p < 0.05) also displayed a substantial decrease. These findings underscore the significant impact of EIF4E inhibition on the expression of VEGFA and CCND1, indicating statistically significant differences.

Protein Expression Profiles in SKOV3 Cells with EIF4E Inhibition and Control Group

Protein expression of EIF4E, VEGFA, and CCND1 was assessed using Western Blot in the 4EGI-1 treatment group and the control group. As presented in Figure 4, the expression of p-EIF4E was significantly lower in the 4EGI-1 treatment group compared to the control group (0.33±0.14 vs. control, p < 0.001). Simultaneously, the expression of VEGFA (0.53±0.18 vs. control, p < 0.01) and CCND1 (0.44±0.16 vs. control, p < 0.001) in the 4EGI-1 treatment group exhibited a marked reduction compared to the control group.

Discussion

EIF4E is a post-transcriptional modification factor that plays a pivotal role in protein synthesis. Recent studies have underscored its critical involvement in various cancers [10]. In the context of ovarian cancer research, elevated EIF4E expression has been observed in late-stage ovarian cancer tissues, with low EIF4E expression correlating to higher survival rates [9]. Suppression of EIF4E expression or function has been shown to inhibit ovarian cancer cell proliferation, invasion, and promote apoptosis. Various compounds and drugs that inhibit EIF4E have been identified, rendering them potential candidates for ovarian cancer treatment [11]. Based on the progressing understanding of EIF4E's role in ovarian cancer, inhibiting EIF4E has emerged as a novel therapeutic avenue for the disease. 4EGI-1, a cap-dependent translation small molecule inhibitor, has been suggested to disrupt the formation of the eIF4E complex [12]. In this study, our analysis of public databases revealed elevated EIF4E expression in ovarian cancer patients compared to normal controls. Furthermore, through treatment with 4EGI-1 in the SKOV3 ovarian cancer cell line, we observed a capacity for 4EGI-1 to inhibit SKOV3 cell spheroid formation. Concurrently, results from PCR and Western Blot analyses demonstrated effective EIF4E inhibition by 4EGI-1. Collectively, 4EGI-1 effectively suppresses EIF4E expression and may exert its effects on ovarian cancer therapy by modulating EIF4E.

Vascular Endothelial Growth Factor (VEGF) is a protein that stimulates angiogenesis and increases vascular permeability, playing a crucial role in tumor growth and metastasis [13]. In ovarian cancer, excessive release of VEGF by tumor cells leads to increased angiogenesis, forming a new vascular network to provide nutrients and oxygen to tumor cells. The formation of new blood vessels enables tumor growth, proliferation, and facilitates tumor cell dissemination into the bloodstream, contributing to distant metastasis [14]. As a significant member of the VEGF family, VEGFA has been extensively studied, and it has been reported that VEGFA expression is notably higher in ovarian cancer tumors [15], consistent with our public database analysis. Furthermore, elevated EIF4E levels have been associated with increased malignant tumor VEGF mRNA translation [16]. Through the use of the EIF4E inhibitor 4EGI-1 in ovarian cancer cell lines, we observed a downregulation in both mRNA and protein expression levels of VEGFA. This suggests that EIF4E inhibition might affect ovarian cancer cell angiogenesis capability through downregulation of VEGF expression.

Cyclin D1 (CCND1) is a cell cycle regulatory protein that participates in controlling cell entry into the S phase and the cell division process. In ovarian cancer, overexpression of CCND1 is associated with increased tumor proliferation activity and poor prognosis [17]. Elevated CCND1 levels promote cell cycle progression, leading to uncontrolled cell proliferation [18]. Additionally, CCND1 can activate cell cycle-related signaling pathways, promoting cancer cell growth and invasion capabilities [19]. Studies have shown that CCND1 gene expression is significantly higher in ovarian cancer tissues compared to normal ovarian tissues [20], potentially promoting proliferation and cell cycle progression through enhanced cyclin D1 translation [9]. Our public database analysis results confirm these observations. Furthermore, treatment with the EIF4E inhibitor 4EGI-1 in ovarian cancer cell lines resulted in varying degrees of downregulation in CCND1 mRNA and protein levels. This indicates that EIF4E inhibition might affect ovarian cancer cell proliferation and cell cycle progression through regulation of CCND1 expression.

In conclusion, overexpression of EIF4E appears to be closely associated with the clinical and pathological characteristics of ovarian cancer patients. In various tumors, EIF4E is significantly correlated with VEGF and cyclin D1, suggesting its role in the regulation of protein translation related to angiogenesis and growth [9, 21]. The correlation analysis results in our study further confirmed the positive correlation among EIF4E, VEGFA, and CCND1 in ovarian cancer. Simultaneous inhibition of EIF4E also led to downregulation of VEGFA and CCND1 expression, validating their interconnectedness. Thus, targeted therapy against EIF4E may prove to be an effective strategy for treating ovarian cancer. However, further research and clinical trials are necessary to assess the safety and efficacy of targeted EIF4E therapy, offering more effective treatment options for ovarian cancer patients.

Acknowledgments:

Funding: This study was supported by the Joint Project of Southwest Medical University and the Affiliated Traditional Chinese Medicine Hospital of Southwest Medical University (Grant No. 2020XYLH-043).

Conflict of Interest: The authors declare no conflicts of interest.

#Ovarian cancer #Eukaryotic translation initiation factor 4E #Vascular endothelial growth factor A #Cyclin D1 #Review Article in Journal of Clinical Case Reports Medical Images and Health Sciences .#jcrmhs

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medchemexpressinhibitor-blog · 1 year ago

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Exploring the Potential of a Glutamine Transporter Inhibitor

Introduction

Cancer cells exhibit distinct metabolic characteristics, and targeting specific metabolic pathways has become an area of intense research in cancer therapeutics. JPH203, a glutamine transporter inhibitor, has emerged as a promising drug candidate for disrupting the metabolic processes crucial to cancer cell survival and proliferation. This article aims to explore factual evidence regarding the efficacy and potential applications of JPH203.

Understanding JPH203

JPH203 is a selective inhibitor of the glutamine transporter ASCT2 (alanine, serine, cysteine-preferring transporter 2). ASCT2 plays a critical role in transporting glutamine, an amino acid essential for cancer cell growth and survival[¹^]. By targeting ASCT2, JPH203 aims to disrupt glutamine uptake and subsequently alter cancer cell metabolism.

The Mechanism of Action

Inhibition of Glutamine Uptake: JPH203 binds to ASCT2, preventing the transport of extracellular glutamine into cancer cells. This disruption hampers the availability of glutamine, an essential nutrient for cancer cell metabolism, thereby impairing their growth and survival[²^].

Factual Evidence Supporting JPH203

Preclinical Studies: Initial preclinical studies have demonstrated the efficacy of JPH203 in inhibiting cancer cell growth across various types of cancers, including lung, breast, pancreatic, and colorectal cancers[³^][⁴^]. These studies have shown that JPH203 treatment led to reduced glutamine uptake, impaired cell proliferation, and increased cell death.

Combination Therapy: JPH203 has been investigated in combination with other anticancer agents, such as chemotherapeutic drugs and targeted therapies. Preclinical studies have suggested synergistic effects when JPH203 is used in combination with other treatments, leading to enhanced anticancer activity[⁵^][⁶^]. These findings highlight the potential of JPH203 as an adjunct therapy to improve treatment outcomes.

Metabolic Reprogramming: Glutamine is a crucial nutrient for cancer cells, serving as a building block for macromolecules and as a source of energy. By inhibiting glutamine uptake, JPH203 disrupts cancer cell metabolism. This metabolic reprogramming can render cancer cells more susceptible to other therapies and potentially overcome drug resistance[⁷^].

Clinical Development

JPH203 is currently undergoing clinical trials to evaluate its safety, tolerability, and efficacy in patients with advanced solid tumors. These studies aim to determine the optimal dosage, treatment duration, and potential side effects to further establish the therapeutic potential of JPH203 in clinical settings[⁸^].

Conclusion

JPH203, a selective inhibitor of the glutamine transporter ASCT2, shows promise as a targeted approach to disrupt cancer cell metabolism. Preclinical studies have demonstrated its ability to inhibit glutamine uptake, impair cancer cell growth, and enhance cell death. The ongoing clinical trials will provide valuable insights into the safety and efficacy of JPH203 in human patients and its potential as part of combination therapies.

While JPH203 holds significant potential as a novel anticancer agent, further research is needed to fully understand its mechanisms of action, optimize treatment strategies, and identify the patient populations that may benefit most from its use. The development of JPH203 represents an exciting advancement in the quest for more effective and targeted cancer therapeutics.please visit MedChemExpress

(Note: This article is for informational purposes only and should not replace professional medical advice. Always consult your healthcare provider for personalized treatment recommendations.)

#biochemistry #business #chemistry #marketing

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justsomeoneintoomanyfandoms · 2 years ago

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HIIII I see that u hv a match up goin on and Id like to try! Would u mind doing one for me with Obey Me?

Pronouns : She/they

Sexuality: Im not sure exactly??... still discovering but I know that I like both sexes

Infp 4w5 / Cancer sun Taurus moon n Scorpio rising (I saw some doing not just the sun sign so i think it would be fun if i include all 3 lol)

Appearance: Im South East Asian. Around 5'2. I hv shoulder length black hair, black eyes and olive toned skin. My hairstyle is akin to the jellyfish hair. I rarely wear makeup and would just hv my bare face out due to its sensitivity to breakouts. And my clothing, its mostly modest/covering for academic places or just comfy and quick with any cool baggy tees i hv. Its my current closet, since i dont hv much occasions to go grand and i just wanna blend in with everyone around me lookin like an npc. But id love to wear more self expressing stuff in the future, to my desire. More accessories, colorful makeups and fashions like dark couquette/gyaru or so!

Personality: My personality, id say its two sided. I guess hv an open mind and easy going (to some degree ofc). A dream chaser and a listener. Sometimes (just sometimes), i can get my mind through a problem and stay grounded. Im also empathic? I like consoling with people and I appreciate the smallest details. I feel for people's struggle and I hold hopes in them. However, i can get moody, its so unexpected and intense that even im scared of it. I can be very quiet then, and dissociative. Id just want to be alone by that time to figure out my situation. Ive been said to appear gloomy or hard to approach too :cry: If im pissed, im venomous. And im actually an anxious person, of all sorts of things. Self deprecating too, i almost forgot abt that. But if i feel suitable, i get funky and enjoy myself hehe.

Likes/Dislikes : I like visual novels, rhythm games and those with good storytelling; a variety of music genres that focus on melody, instrument, composing; local asian food; sleeping with plushies; arts n crafts; esoteric things; philosophy study; my friends; solitude and continuation; aesthetic or hidden values and uhhh nice, mannered intriguing people.

I dont like smelly people doe. People who are narrow minded icks me oops. Pls dont tryna barge in on me when im busy unless it helps. I hate the sun... And not getting myself tented after a long day. I dislike my parents as well, yikes. Worst of all, being opressed.

Hobbies : doll, bracelet making; drawing, online shopping, rhythm game arcade, reading philosophy works, uhh getting invested in random medias...

Anyways, thats my submission! If u do reply, tysm for the matchup!!!

Hi Anon! Thank you for the request! I hope you like your matchup!

In Obey Me, I match you with...

Asmo is the best person to hype you up about wearing more self-expressing things. He’s great at putting outfits together and will give you honest and genuine feedback.

Doesn’t mind your personality changes. He knows what mood swings are like so he’s very understanding.

Please go online shopping with him! But set a budget because you’re both liable to get caught up in the energy and spend too much. But online shopping with Asmo would be so much fun.

Not great at giving you alone time but if you say you need some space, he’ll respect your wishes. While you’re enjoying your alone time, he’ll do a spa day or hang out with some of his friends.

Asmo loves your plushies. He thinks they’re really cute and, if you’re okay with it, would love to borrow some of them to sleep with as well. He’ll take good care of them and swaps them out occasionally so you’ve got a constantly rotating roster of plushies in your room.

#writing #fanfic #matchup #matchup request #request #obey me #obey me shall we date #obey me nightbringer #asmodeus

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ariel-seagull-wings · 2 years ago

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JANINE AND EGON'S WEDDING QUESTIONS (MOVIE, NOVELIZATION AND COMICS VERSE)

@spengnitzed @bixiebeet @professorlehnsherr-almashy @angelixgutz

Imagine what music they'd have? What food? Would it be outside? What kind of theme, if any, would they have?

Jazz and jewish folk music. The ceremony would be outside in the garden, while the dinner reception, with Ashkenazi jewish food from Poland, Russia and Ukraine and the dancing party would be inside the house of their friend, Ray. The theme would be woodlands and mycology.

Who would they invite?

Ray (who is Egon's best man and provider of the house where the wedding is celebrated), Winston, Peter, Dana, Egon's mother, brother, sister-in-law and baby nephew, Janine's parents, sister, grandmother and maternal uncles and cousins.

What season is it? Day or night? What colors do people wear?

Autumn, evening till night, starting at 15:00 pm. While the decoration is green and brown, the guests are left free to choose the colors of their clothes.

Is it traditional or do they do something wild?

The ceremony follows traditional jewish marriage rituals, along with including a justice of peace to assist the civil legalization and documentation of the wedding.

Did they write their own vows? Who is the priest/priestess/minister marrying you? Or is it a family member or other platonic F/O?

They do write their own vows, taking some inspiration from literature. Janine's family rabbi and a paid justice of peace marries her and Egon.

Are they wearing suits? Dresses? Something else entirely?

Janine wears a tea-length dress with a lace top and puffy skirt.

Egon wears a black suit and bowtie.

What is their cake like if they have one?

Is a cake decorated with candy mushrooms and sugar leafs, topped with two snails representing the couple.

Do they throw the bouquet for someone to catch or do they pass out one flower to everyone so they let everyone know they are worthy of love?

Janine appears like she will throw one bouquet to one person, then surprises everyone when the flowers are untied and everybody catches a flower.

Do they have a party afterwards? What music?

A dancing party with the music of Cleo Laine, Harry Belafonte, Ofra Haza and The Parvarim.

What is their honeymoon like? Is it a stay at home one? Do they go somewhere exciting? How long is their trip?

A three week vacation to San Diego, California.

How many kids do they have? What are their names?

Three kids: Noemi, Tobin and Batya.

NICKNAME(S): Baby Smurf, Sugar Plum.

FACECLAIM: Violet Ramis (child), Jenny Slate (adult).

BIRTH: August 25th 1984.

ZODIAC SIGN: Virgo.

SEXUALITY: Bissexual.

GENDER: Female.

ORIGIN: Forest Hills, Queens, New York City.

NATIONALITY: US American.

CHARACTERISTICS:

+ Curious, inquisitive, creative, extroverted, with a fascination for gallows humor;

+ Loves colorful clothes, cartoons and comic books;

+ Has a strong temper and rarely disguises when she has either contempt or desire to kill someone she perceives as an enemy;

WEAPON OF CHOICE:

+ P.K.E Meter

+ Proton Pack

+ Ghost Trap

OTHER PERSONAL INFO:

+ While she inherited the academic talent of her father, she has the more outgoing and bold approach to social interactions of her mother;

+ Considers the other Ghostbusters her uncles, with Ray and Winston being her favorites;

+ Is a huge fan of the Smurfs and Asterix comics and cartoons and a cosplayer;

+ Before deciding to pursue a career in STEM and Parapsychology, for a while she considered taking religious studies to become a rabbi. While she didn't went through with that, she still became and expert in Jewish Mythology and Folklore;

+ Besides being a Ghostbuster, Noemi also teaches about the paranormal at Columbia University.

NICKNAME(S): Bean Bunny.

FACECLAIM: Anton Yelchin (child and adult).

BIRTH: June 23th 1989.

ZODIAC SIGN: Cancer.

SEXUALITY: Asexual.

GENDER: Male.

ORIGIN: Forest Hills, Queens, New York City.

NATIONALITY: US American.

CHARACTERISTICS:

+ Calm, caring, empathetic, studious, who enjoys safety and tranquility;

+ Loves cooking, gardening and drawing;

+ Is anxious and gets stuck in a place when frightened;

WEAPON OF CHOICE:

+ P.K.E Meter

+ Ghost Trap

OTHER PERSONAL INFO:

+ Has the more quiet temperament of his father, and the belief in intuition from his mother, wich is formative of his view of science mainly as an instrument of nurturing;

+ Collects mold, spores and fungus, and also enjoys botanics, specially harvesting the mushrooms, fruits and vegetables to use in dishes he cooks for his friends and family;

+ Loves the Pogo comic strips, Fraggle Rock and the Dave the Gnome cartoon;

+ Studies to become a Landscape Architect, Environmental Engineer and Manager;

+ When reluctantly involved in Ghostbusting by his older sister, he only uses the P.K.E Meter and the Ghost Trap, seeing these instruments as something to try to communicate with the ghosts and help them get shelter and defend humans from harm, but he doesn’t handle the Proton Pack because is heavy and because he sees it as a intimidating gun.

NICKNAME(S): Ladybug.

FACECLAIM: Flora Guiet (child), Alexandra Socha (adult).

BIRTH: September 29th 1991.

ZODIAC SIGN: Libra.

SEXUALITY: Biromantic and demisexual.

GENDER: Female.

ORIGIN: Forest Hills, Queens, New York City.

NATIONALITY: US American.

CHARACTERISTICS:

+ Likes to keep things well organized to facilitate the work and everyday life of other people;

+ Physically agile;

+ In a conversation, can see connections between topics that the other person listening her would never imagine being related;

WEAPON OF CHOICE:

+Walkie-talkie

+Proton Pack

+Ghost Trap

+ Ecto Goggles

OTHER PERSONAL INFO:

+ Inherited her mother’s taste for racquetball, and also plays tennis;

+ Loves RPG, be they tabletop or video games, eventually getting a Masters Degree in Game Theory and Game Design;

+ Is fascinated with prehistoric animals, studying History, Biology, Zoology, Archeology and Paleontology, the area where she intends to become a Doctor;

+ Also enjoys photography;

+ Is a mix between a Explorer Historian, whose greatest pleasure is delving into the new world that they are exploring in search of knowledge as the greatest reward, and a Socializer Strategist, happy to collaborate in order to achieve bigger and better things than she could on her own, while having no problems assuming leadership if it means keeping the group safe and sound when the situation becomes especially dangerous.

Where do they live?

In an old two storey boarding house in Forest Hills, Queens, chosen because it looked similar to a drawing that Janine made in her childhood of her dream house, which should be old and covered with vines like the house that served as Madeline's boarding school.

#tumblr mutuals #fandom musings #ghostbusters 1984 #egon spengler #janine melnitz #harold ramis #annie potts #janegon #spengnitz #egonine

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screenshots123 · 2 years ago

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📅 Aug 2023 📰 New mRNA-based malaria vaccine shows promise in preclinical trials 🗞 News-Medical.net

The focus of the collaborative research investigating a novel target for malaria was originally on peptide-based vaccines. However, in 2018, the team shifted their approach and started investigating RNA-based vaccines – a decision that, so far, seems to have paid off with the recent success of RNA technology in vaccine development.

"While our successful peptide-based vaccines targeting malaria only contain small protein fragments of a malaria protein, mRNA vaccines encode an entire malaria protein," says the University of Melbourne's Dr Lauren Holz, Research Officer at the Doherty Institute and co-author of the paper.

To pack an extra protective punch, the mRNA vaccine has been combined with an adjuvant – originally developed at the Malaghan and Ferrier Institutes for cancer immunotherapies – which targets and stimulates liver-specific immune cells. This additional ingredient helps localise the RNA vaccine response to the liver, a key site in preventing the parasite from developing and maturing in the body.

"When the parasite first enters the bloodstream, it travels to the liver where it develops and matures before going on to infect blood cells, which is when disease symptoms occur," says Dr Mitch Ganley, Postdoctoral Research Fellow at the Ferrier Research Institute, and co-author of the study.

"Unlike the COVID-19 vaccine that works by neutralizing antibodies, our unique approach relies on T-cells which play a critical role in immunity. Specifically, a type of T-cell called a tissue-resident memory T-cell, that halts malaria infection in the liver to completely stop the spread of infection."

Dr Holz says the key advantage of this vaccine is that it isn't affected by previous exposure to malaria.

"A lot of malaria vaccines undergoing trials have worked really well in animal models or when they're given to people who haven't had malaria before, but they don't work well when given to people living in malaria-endemic regions. In contrast, our vaccine is still capable of generating protective liver-specific immune cells and providing protection even when the animal models have been pre-exposed to the disease," says Dr Holz.

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digitalmore · 1 day ago

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#IFTTT #Digital More

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crimsonpublisherscancerstudy · 9 months ago

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Unstipulated and InexactIndeterminate Dendritic Cell Tumour_Crimson Publishers

Opinion

Indeterminate dendritic cell tumour emerges as an extremely exceptional tumefaction composed of proliferation of dendritic cells or cells of histiocytic lineage. Additionally designated as indeterminate cell histiocytosis, indeterminate cell tumour or indeterminate dendritic cell tumour, true cutaneous dendritic cell tumour may depict solitary or multifocal lesions. Generally, tumefaction is confined to diverse cutaneous surfaces wherein deep seated visceral or regional lymph node involvement is exceptional. Tumour forming indeterminate cells simulate Langerhans cells vis-à-vis morphological and antigenic features. However, indeterminate cells appear devoid of Birbeck granules and lack immune reactivity to langerin (CD207). Median age of disease emergence is 45 years although no age of disease occurrence is exempt. An almost equivalent gender predilection is encountered. Indeterminate dendritic cell tumour predominantly(~88%) implicates diverse cutaneous surfaces. Infrequently, regional lymph nodes (9%) or spleen (2.3%) may be involved [1,2]. Of obscure a etiology, neoplasm expounds varied concurrence between indeterminate cells and Langerhans cells as ~indeterminate cells manifest as Langerhans cells devoid of Birbeck granules ~indeterminate cells represent as immature Langerhans cells. A subset of neoplasms express dendritic cell marker ZBTB46, thereby indicating the emergence of neoplasms directly from bone marrow progenitors, in contrast to embryonic precursors which undergo localized cutaneous regeneration [1,2].

Read more about this article:

For more articles in Novel Approaches in Cancer Study

#cancer #breast cancer #crimson cancer #crimson publishers #novel approaches in cancer study #open access journal #crimson nacs

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pcrtisuyog · 5 days ago

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The Global Impact of Clinical Research: Bridging Innovation and Patient Care

Clinical research has long been the cornerstone of medical advancement, offering hope where there once was none and bringing innovative treatments closer to patients around the world. From discovering life-saving drugs to improving public health protocols, the global impact of clinical research is vast, profound, and deeply human. It connects laboratories with lives, data with decisions, and innovation with healing.

In today’s healthcare landscape, this bridge between innovation and patient care is more important than ever. With the fast-paced evolution of diseases, new technologies, and growing health concerns globally, clinical research serves as the thread that weaves together scientific discovery with compassionate healthcare delivery.

What is clinical research?

Clinical research refers to studies conducted with human participants aimed at evaluating medical, surgical, or behavioural interventions. These studies may investigate:

New medications or drug combinations

New medical devices

Innovative treatment approaches

Preventive strategies

Diagnostic tools

Quality of life improvements

Whether it’s a new cancer drug or a vaccine for a virus, it all begins with rigorous, regulated research.

The Global Reach of Clinical Trials

Today, clinical trials are not confined to just one part of the world. They are a global effort, uniting researchers, healthcare providers, and patients across countries and continents. This international collaboration has multiple benefits:

Diverse Population Studies: Helps ensure the safety and effectiveness of treatments across different ethnicities and genetic backgrounds.

Faster Enrolment and Data Collection: Speeds up the research process.

Shared Medical Advancements: Breakthroughs made in one part of the world often benefit patients everywhere.

Countries like the United States, Germany, India, China, and Brazil are actively involved in various stages of clinical trials, helping to accelerate access to novel treatments.

Pune Clinical Research: A Growing Global Contributor

Among emerging centres of excellence in India, Pune clinical research is steadily gaining global recognition. With its blend of academic institutions, hospitals, skilled professionals, and research infrastructure, Pune has become a hub for conducting ethical and quality-focused clinical trials.

Here's why Pune clinical research is making headlines:

Highly Skilled Workforce: Pune boasts a pool of trained clinical research professionals, physicians, and data analysts.

World-Class Training Institutes: Institutions like Pune Clinical Training Institute (PCTI) are empowering young professionals with hands-on experience and globally aligned knowledge.

Ethical Oversight: Regulatory bodies and ethics committees ensure every trial meets stringent global and national guidelines.

Strong Hospital Network: Multispecialty hospitals and research centres collaborate for trial execution.

This ecosystem is helping Pune become a trusted location for multinational pharmaceutical companies and biotech firms to conduct their trials with confidence.

The Human Side of Research

While data, protocols, and approvals are essential in clinical research, at its core, it is about people—those who participate in trials, those who design them, and those who benefit from their outcomes.

Volunteers and Patients: Clinical trials often depend on the courage of individuals who enrol in them, driven by the hope of a cure for themselves or future generations.

Care Providers and Researchers: Doctors, nurses, and research coordinators offer not just expertise but also empathy and support throughout the trial process.

Families and Communities: The impact of a successful clinical trial often transforms entire communities, improving quality of life and health standards.

Key Contributions of Clinical Research

Advancing Personalised Medicine: Tailoring treatments to individual patients based on their genetic profile.

Combating Global Health Crises: From COVID-19 vaccines to HIV treatments, research is our strongest tool.

Enhancing Drug Safety: Ensures that treatments are not only effective but safe in the long run.

Reducing Healthcare Costs: Prevention and early diagnosis can lower the financial burden on healthcare systems.

Driving Medical Innovation: Facilitates the development of smart devices, AI-based diagnostics, and biotech therapies.

Bridging the Gap: From Innovation to Patient Care

Clinical research plays a bridging role, turning a scientific hypothesis into a healing solution. The process is complex, involving multiple phases—from lab research to human trials—but the end goal is always the same: better health outcomes for patients.

In India and globally, including through Pune clinical research, this bridge is growing stronger each day. As more professionals get trained, more ethical frameworks are enforced, and more patients get access to new therapies, the positive ripple effect will continue to expand.

Conclusion

The global impact of clinical research cannot be overstated. It stands at the intersection of science, care, and hope. As centres like Pune clinical research contribute to this ever-growing field, we move closer to a world where every patient has access to advanced, effective, and affordable healthcare solutions.

Clinical research is not just about discovering new treatments—it’s about changing lives, one study at a time.

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sunaleisocial · 6 days ago

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Biologists identify targets for new pancreatic cancer treatments

New Post has been published on https://sunalei.org/news/biologists-identify-targets-for-new-pancreatic-cancer-treatments/

Biologists identify targets for new pancreatic cancer treatments

Researchers from MIT and Dana-Farber Cancer Institute have discovered that a class of peptides expressed in pancreatic cancer cells could be a promising target for T-cell therapies and other approaches that attack pancreatic tumors.

Known as cryptic peptides, these molecules are produced from sequences in the genome that were not thought to encode proteins. Such peptides can also be found in some healthy cells, but in this study, the researchers identified about 500 that appear to be found only in pancreatic tumors.

The researchers also showed they could generate T cells targeting those peptides. Those T cells were able to attack pancreatic tumor organoids derived from patient cells, and they significantly slowed down tumor growth in a study of mice.

“Pancreas cancer is one of the most challenging cancers to treat. This study identifies an unexpected vulnerability in pancreas cancer cells that we may be able to exploit therapeutically,” says Tyler Jacks, the David H. Koch Professor of Biology at MIT and a member of the Koch Institute for Integrative Cancer Research.

Jacks and William Freed-Pastor, a physician-scientist in the Hale Family Center for Pancreatic Cancer Research at Dana-Farber Cancer Institute and an assistant professor at Harvard Medical School, are the senior authors of the study, which appears today in Science. Zackery Ely PhD ’22 and Zachary Kulstad, a former research technician at Dana-Farber Cancer Institute and the Koch Institute, are the lead authors of the paper.

Cryptic peptides

Pancreatic cancer has one of the lowest survival rates of any cancer — about 10 percent of patients survive for five years after their diagnosis.

Most pancreatic cancer patients receive a combination of surgery, radiation treatment, and chemotherapy. Immunotherapy treatments such as checkpoint blockade inhibitors, which are designed to help stimulate the body’s own T cells to attack tumor cells, are usually not effective against pancreatic tumors. However, therapies that deploy T cells engineered to attack tumors have shown promise in clinical trials.

These therapies involve programming the T-cell receptor (TCR) of T cells to recognize a specific peptide, or antigen, found on tumor cells. There are many efforts underway to identify the most effective targets, and researchers have found some promising antigens that consist of mutated proteins that often show up when pancreatic cancer genomes are sequenced.

In the new study, the MIT and Dana-Farber team wanted to extend that search into tissue samples from patients with pancreatic cancer, using immunopeptidomics — a strategy that involves extracting the peptides presented on a cell surface and then identifying the peptides using mass spectrometry.

Using tumor samples from about a dozen patients, the researchers created organoids — three-dimensional growths that partially replicate the structure of the pancreas. The immunopeptidomics analysis, which was led by Jennifer Abelin and Steven Carr at the Broad Institute, found that the majority of novel antigens found in the tumor organoids were cryptic antigens. Cryptic peptides have been seen in other types of tumors, but this is the first time they have been found in pancreatic tumors.

Each tumor expressed an average of about 250 cryptic peptides, and in total, the researchers identified about 1,700 cryptic peptides.

“Once we started getting the data back, it just became clear that this was by far the most abundant novel class of antigens, and so that’s what we wound up focusing on,” Ely says.

The researchers then performed an analysis of healthy tissues to see if any of these cryptic peptides were found in normal cells. They found that about two-thirds of them were also found in at least one type of healthy tissue, leaving about 500 that appeared to be restricted to pancreatic cancer cells.

“Those are the ones that we think could be very good targets for future immunotherapies,” Freed-Pastor says.

Programmed T cells

To test whether these antigens might hold potential as targets for T-cell-based treatments, the researchers exposed about 30 of the cancer-specific antigens to immature T cells and found that 12 of them could generate large populations of T cells targeting those antigens.

The researchers then engineered a new population of T cells to express those T-cell receptors. These engineered T cells were able to destroy organoids grown from patient-derived pancreatic tumor cells. Additionally, when the researchers implanted the organoids into mice and then treated them with the engineered T cells, tumor growth was significantly slowed.

This is the first time that anyone has demonstrated the use of T cells targeting cryptic peptides to kill pancreatic tumor cells. Even though the tumors were not completely eradicated, the results are promising, and it is possible that the T-cells’ killing power could be strengthened in future work, the researchers say.

Freed-Pastor’s lab is also beginning to work on a vaccine targeting some of the cryptic antigens, which could help stimulate patients’ T cells to attack tumors expressing those antigens. Such a vaccine could include a collection of the antigens identified in this study, including those frequently found in multiple patients.

This study could also help researchers in designing other types of therapy, such as T cell engagers — antibodies that bind an antigen on one side and T cells on the other, which allows them to redirect any T cell to kill tumor cells.

Any potential vaccine or T cell therapy is likely a few years away from being tested in patients, the researchers say.

The research was funded in part by the Hale Family Center for Pancreatic Cancer Research, the Lustgarten Foundation, Stand Up To Cancer, the Pancreatic Cancer Action Network, the Burroughs Wellcome Fund, a Conquer Cancer Young Investigator Award, the National Institutes of Health, and the National Cancer Institute.

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oaresearchpaper · 8 days ago

Link

#Green synthesis #Lychee honey #Maghemite nanoparticles #Cancer hyperthermia #Superparamagnetic properties #Sustainable nanotechnology

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silveredmarionetteelement · 12 days ago

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Decoding Disease with Exosomes: A Novel Diagnostic Approach?

Introduction

In the ever-evolving landscape of medical diagnostics, researchers and clinicians continually seek more effective, non-invasive methods to detect and manage diseases. One exciting frontier in this quest is the study of exosomes. These tiny extracellular vesicles, originating from cells, are emerging as powerful biomarkers for various conditions. This article explores the potential of exosomes in disease diagnosis and treatment, focusing on their implications for precision medicine.

What Are Exosomes? Understanding Exosomes and Their Functionality

Exosomes are nano-sized vesicles ranging from 30 to 150 nanometers in diameter, released by cells into the extracellular environment. They play a pivotal role in intercellular communication, transporting proteins, lipids, and nucleic acids between cells. Their ability to carry molecular signatures reflective of their cell of origin positions https://www.exosomestherapy.co.uk/ them as promising candidates for diagnostic applications.

The Composition of Exosomes

Exosomes are composed of a lipid bilayer encapsulating various biomolecules:

Proteins: Include receptors and signaling molecules. Lipids: Provide structural integrity and influence membrane interactions. Nucleic Acids: Such as mRNA and microRNA that can regulate gene expression.

This unique composition allows exosomes to reflect the physiological state of their parent cells accurately.

Decoding Disease with Exosomes: A Novel Diagnostic Approach? Exosome Isolation Techniques

To leverage exosomes for diagnostic purposes, efficient isolation techniques are essential. Common methods include:

Ultracentrifugation: The gold standard but time-consuming. Size-exclusion chromatography: Effective in separating exosome populations based on size. Magnetic bead-based methods: Allow for rapid isolation using specific surface markers. Diagnostic Applications of Exosomes

Exosome analysis holds significant promise in diagnosing a range of diseases:

Cancer Diagnostics

Exosomal biomarkers offer insights into tumor presence and progression:

Breast Cancer: Specific miRNAs identified in exosomal profiles correlate with tumor stages. Lung Cancer: Protein signatures found in exosomes can predict patient survival rates. Neurological Disorders

Exosome profiling may aid in early diagnosis:

Alzheimer’s Disease: Changes in exosomal cargo could signal disease onset before clinical symptoms appear. Parkinson's Disease: Specific protein markers have been found in the exosomal profiles of affected individuals. Cardiovascular Diseases

Exosomal content reflects cardiovascular health:

Elevated levels of certain miRNAs have been linked to heart failure. Exosome Therapy: An Innovative Approach to Treatment What is Exosome Therapy?

Exosome exosome therapy studies therapy harnesses the regenerative properties of stem cell-derived exosomes for therapeutic applications

youtube

#Youtube

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irrespub · 13 days ago

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Exploring the Role of Journals in Advancing Medical Research

The world of medical science has witnessed significant advancements over the past few decades, owing much of its progress to the rigorous research published in peer-reviewed journals. Among these, the international journal of cancer and the Indian journal of pharmacology stand out as crucial platforms for the dissemination of knowledge. These journals play a vital role in connecting researchers, healthcare professionals, and academic institutions, allowing for a collaborative exchange of ideas and breakthroughs. From uncovering novel treatment methods to understanding drug interactions, such journals shape the future of medical science.

The international journal of cancer has consistently contributed to the field by publishing studies focused on cancer biology, prevention, and treatment. It serves as a bridge between clinical and laboratory research, ensuring that innovative findings are not confined to the lab but are translated into practical solutions for patients worldwide. Cancer research is inherently complex and requires a multidisciplinary approach. Journals like this provide a space where oncologists, molecular biologists, geneticists, and pharmacologists can converge to share and critique findings that have real-world applications.

Similarly, the Indian journal of pharmacology is instrumental in advancing pharmaceutical research in India and beyond. It provides insights into drug development, pharmacokinetics, and clinical pharmacology. The journal also highlights the importance of understanding regional health challenges and the role of locally developed drugs in combating them. This regional perspective is particularly valuable in a global context, where treatment protocols need to be tailored to the genetic and environmental background of specific populations. Furthermore, the publication promotes ethical practices in drug testing and the use of evidence-based medicine.

One of the most significant impacts of journals such as these is their influence on policy and clinical guidelines. When regulatory bodies look to revise healthcare policies or introduce new treatment protocols, they often rely on the data and recommendations found in reputable publications. Articles published in high-impact journals are reviewed and referenced extensively, making them a foundation for decision-making in both government and private sectors. This highlights the importance of maintaining scientific integrity and transparency in all published research.

Moreover, academic journals are essential in supporting the career growth of researchers and scholars. By providing a credible platform to publish their work, journals contribute to the academic reputation of authors and institutions. They also foster innovation by exposing readers to new methodologies, tools, and research approaches. For students and emerging scientists, reading such journals is an indispensable part of their training and education, offering a glimpse into the challenges and triumphs of real-world medical research.

Irrespub.com recognizes the importance of such platforms in nurturing a well-informed global research community. By offering access to curated and peer-reviewed content, the site aligns itself with the goal of facilitating knowledge exchange across borders. It is through these initiatives that global health concerns can be addressed more effectively, fostering international collaboration in the fight against diseases.

The rapid evolution of digital technologies has also transformed the way academic content is accessed and shared. Open-access models and online repositories now make it easier for researchers from remote and under-resourced regions to stay informed and contribute to the scientific dialogue. Journals that adopt such models can amplify their reach and impact, ensuring that knowledge is not limited by geography or institutional affiliation. This democratization of information plays a crucial role in creating a more equitable scientific community.

As the volume of scientific literature continues to grow, it becomes increasingly important to uphold standards of quality and relevance. Peer review, editorial oversight, and transparent publication practices are essential to maintain the credibility of academic journals. Both the international journal of cancer and the Indian journal of pharmacology exemplify these standards, reinforcing their reputation as reliable sources of scientific knowledge.

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