#chemoresistance

[indogenmed-org]

Researchers have found that combining CDK4/6 inhibitors with chemotherapy significantly slows tumor growth in small cell lung cancer (SCLC). This new approach works by blocking key pathways involved in cancer cell survival, offering hope for patients battling chemoresistance. Could this be the next step in advanced SCLC treatment.

[gendronrecherche]

Reversing Chemoresistance in Pancreatic Cancer

Researchers discover that pancreatic cancer's chemoresistance is linked to tissue stiffness and CD44 receptors, suggesting new drug targets. http://dlvr.it/T9Bpsr

[rnomics]

IJMS, Vol. 25, Pages 6740: LINC00662 Promotes Aggressive Traits by Modulating OCT4 Expression through miR-335-5p in Gallbladder #cancer Cells

Long non-coding #RNAs (l#ncRNAs) are nucleotide sequences that participate in different biological processes and are associated with different pathologies, including #cancer. Long intergenic non-protein-coding #RNA 662 (LINC00662) has been reported to be involved in different #cancers, including colorectal, prostate, and breast #cancer. However, its role in gallbladder #cancer has not yet been described. In this article, we hypothesize that LINC00662 has an important role in the acquisition of aggressiveness traits such as a stem-like phenotype, invasion, and chemoresistance in gallbladder #cancer. Here, we show that LINC00662 is associated with larger tumor size and lymph node metastasis in patients with gallbladder #cancer. Furthermore, we show that the overexpression of LINC00662 promotes an increase in CD133+/CD44+ cell populations and the expression of stemness-associated genes. LINC00662 promotes greater invasive capacity and the expression of genes associated with epithelial–mesenchymal transition. In addition, the expression of LINC00662 promotes resistance to cisplatin and 5-fluorouracil, associated with increased expression of chemoresistance-related ATP-binding cassette (ABC) transporters in gallbladder #cancer (GBC) cell lines. Finally, we show that the mechanism by which LINC00662 exerts its function is through a decrease in #microRNA 335-5p (miR-335-5p) and an increase in octamer-binding transcription factor 4 (OCT4) in GBC cells. Thus, our data allow us to propose LINC00662 as a biomarker of poor prognosis and a potential therapeutic target for patients with GBC. https://www.mdpi.com/1422-0067/25/12/6740?utm_source=dlvr.it&utm_medium=tumblr

[jcmarchi]

From steel engineering to ovarian tumor research

New Post has been published on https://thedigitalinsider.com/from-steel-engineering-to-ovarian-tumor-research/

From steel engineering to ovarian tumor research

Ashutosh Kumar is a classically trained materials engineer. Having grown up with a passion for making things, he has explored steel design and studied stress fractures in alloys.

Throughout Kumar’s education, however, he was also drawn to biology and medicine. When he was accepted into an undergraduate metallurgical engineering and materials science program at Indian Institute of Technology (IIT) Bombay, the native of Jamshedpur was very excited — and “a little dissatisfied, since I couldn’t do biology anymore.”

Now a PhD candidate and a MathWorks Fellow in MIT’s Department of Materials Science and Engineering, Kumar can merge his wide-ranging interests. He studies the effect of certain bacteria that have been observed encouraging the spread of ovarian cancer and possibly reducing the effectiveness of chemotherapy and immunotherapy.

“Some microbes have an affinity toward infecting ovarian cancer cells, which can lead to changes in the cellular structure and reprogramming cells to survive in stressful conditions,” Kumar says. “This means that cells can migrate to different sites and may have a mechanism to develop chemoresistance. This opens an avenue to develop therapies to see if we can start to undo some of these changes.”

Kumar’s research combines microbiology, bioengineering, artificial intelligence, big data, and materials science. Using microbiome sequencing and AI, he aims to define microbiome changes that may correlate with poor patient outcomes. Ultimately, his goal is to engineer bacteriophage viruses to reprogram bacteria to work therapeutically.

Kumar started inching toward work in the health sciences just months into earning his bachelor’s degree at IIT Bombay.

“I realized engineering is so flexible that its applications extend to any field,” he says, adding that he started working with biomaterials “to respect both my degree program and my interests.”

“I loved it so much that I decided to go to graduate school,” he adds.

Starting his PhD program at MIT, he says, ���was a fantastic opportunity to switch gears and work on more interdisciplinary or ‘MIT-type’ work.”

Kumar says he and Angela Belcher, the James Mason Crafts Professor of biological engineering and materials science, began discussing the impact of the microbiome on ovarian cancer when he first arrived at MIT.

“I shared my enthusiasm about human health and biology, and we started brainstorming,” he says. “We realized that there’s an unmet need to understand a lot of gynecological cancers. Ovarian cancer is an aggressive cancer, which is usually diagnosed when it’s too late and has already spread.”

In 2022, Kumar was awarded a MathWorks Fellowship. The fellowships are awarded to School of Engineering graduate students, preferably those who use MATLAB or Simulink — which were developed by the mathematical computer software company MathWorks — in their research. The philanthropic support fueled Kumar’s full transition into health science research.

“The work we are doing now was initially not funded by traditional sources, and the MathWorks Fellowship gave us the flexibility to pursue this field,” Kumar says. “It provided me with opportunities to learn new skills and ask questions about this topic. MathWorks gave me a chance to explore my interests and helped me navigate from being a steel engineer to a cancer scientist.”

Kumar’s work on the relationship between bacteria and ovarian cancer started with studying which bacteria are incorporated into tumors in mouse models.

“We started looking closely at changes in cell structure and how those changes impact cancer progression,” he says, adding that MATLAB image processing helps him and his collaborators track tumor metastasis.

The research team also uses RNA sequencing and MATLAB algorithms to construct a taxonomy of the bacteria.

“Once we have identified the microbiome composition,” Kumar says, “we want to see how the microbiome changes as cancer progresses and identify changes in, let’s say, patients who develop chemoresistance.”

He says recent findings that ovarian cancer may originate in the fallopian tubes are promising because detecting cancer-related biomarkers or lesions before cancer spreads to the ovaries could lead to better prognoses.

As he pursues his research, Kumar says he is extremely thankful to Belcher “for believing in me to work on this project.

“She trusted me and my passion for making an impact on human health — even though I come from a materials engineering background — and supported me throughout. It was her passion to take on new challenges that made it possible for me to work on this idea. She has been an amazing mentor and motivated me to continue moving forward.”

For her part, Belcher is equally enthralled.

“It has been amazing to work with Ashutosh on this ovarian cancer microbiome project,” she says. “He has been so passionate and dedicated to looking for less-conventional approaches to solve this debilitating disease. His innovations around looking for very early changes in the microenvironment of this disease could be critical in interception and prevention of ovarian cancer. We started this project with very little preliminary data, so his MathWorks fellowship was critical in the initiation of the project.”

Kumar, who has been very active in student government and community-building activities, believes it is very important for students to feel included and at home at their institutions so they can develop in ways outside of academics. He says that his own involvement helps him take time off from work.

“Science can never stop, and there will always be something to do,” he says, explaining that he deliberately schedules time off and that social engagement helps him to experience downtime. “Engaging with community members through events on campus or at the dorm helps set a mental boundary with work.”

Regarding his unusual route through materials science to cancer research, Kumar regards it as something that occurred organically.

“I have observed that life is very dynamic,” he says. “What we think we might do versus what we end up doing is never consistent. Five years back, I had no idea I would be at MIT working with such excellent scientific mentors around me.”

[leedsomics]

Phenomics demonstrates cytokines additive induction of epithelial to mesenchymal transition

Epithelial to Mesenchymal Transition (EMT) is highly plastic with a program where cells lose adhesion and become more motile. EMT heterogeneity is one of the factors for disease progression and chemoresistance in cancer. Omics characterizations are costly and challenging to use. We developed single cell phenomics with easy to use wide-field fluorescence microscopy. We analyse over 70000 cells and combined 51 features. Our simplistic pipeline allows efficient tracking of EMT plasticity, with a single statistical metric. We discriminate four high EMT plasticity cancer cell lines along the EMT spectrum. We test two cytokines, inducing EMT in all cell lines, alone or in combination. The single cell EMT metrics demonstrate the additive effect of cytokines combination on EMT independently of cell line EMT spectrum. Single cell phenomics is uniquely suited to characterize the cellular heterogeneity in response to complex microenvironment, and show potential for drug testing assays. http://dlvr.it/T6bMGF

[jhavelikes]

Brain metastasis of advanced breast cancer often results in deleterious consequences. Metastases to the brain lead to significant challenges in treatment options, as the blood–brain barrier (BBB) prevents conventional therapy. Thus, we hypothesized that creation of a nanoparticle (NP) that distributes to both primary tumor site and across the BBB for secondary brain tumor can be extremely beneficial. Here, we report a simple targeting strategy to attack both the primary breast and secondary brain tumors utilizing a single NP platform. The nature of these mitochondrion-targeted, BBB-penetrating NPs allow for simultaneous targeting and drug delivery to the hyperpolarized mitochondrial membrane of the extracranial primary tumor site in addition to tumors at the brain. By utilizing a combination of such dual anatomical distributing NPs loaded with therapeutics, we demonstrate a proof-of-concept idea to combat the increased metabolic plasticity of brain metastases by lowering two major energy sources, oxidative phosphorylation (OXPHOS) and glycolysis. By utilizing complementary studies and genomic analyses, we demonstrate the utility of a chemotherapeutic prodrug to decrease OXPHOS and glycolysis by pairing with a NP loaded with pyruvate dehydrogenase kinase 1 inhibitor. Decreasing glycolysis aims to combat the metabolic flexibility of both primary and secondary tumors for therapeutic outcome. We also address the in vivo safety parameters by addressing peripheral neuropathy and neurobehavior outcomes. Our results also demonstrate that this combination therapeutic approach utilizes mitochondrial genome targeting strategy to overcome DNA repair–based chemoresistance mechanisms.

Simultaneous targeting of peripheral and brain tumors with a therapeutic nanoparticle to disrupt metabolic adaptability at both sites | PNAS

[petnews2day]

Purdue researchers see possible link with dog, human cancer treatments – 95.3 MNC

New Post has been published on https://petn.ws/1Y0cp

Purdue researchers see possible link with dog, human cancer treatments – 95.3 MNC

In the first experiment of its kind, Purdue University researchers treated canines diagnosed with cancer using chemotherapy to see if their response could lead to future treatment for human cancer patients. Chemoresistance, a patient’s adverse reaction to chemotherapy, can lessen remission and survival time. Michael Childress, professor of comparative oncology in the College of Veterinary […]

See full article at https://petn.ws/1Y0cp #DogNews

[tumimmtxpapers]

Correction: IL6 derived from cancer-associated fibroblasts promotes chemoresistance via CXCR7 in esophageal squamous cell carcinoma

No abstract http://dlvr.it/SwJgrC

[ribosome-papers]

Targeting Ribosome Biogenesis as a Novel Therapeutic Approach to Overcome EMT-related Chemoresistance in Breast Cancer

Pubmed: http://dlvr.it/Ss79b0

[indogenmed-org]

Pancreatic adenocarcinoma is the fourth leading cause of cancer deaths, fueled by cancer stem cells driving drug resistance. 🧬 Research shows BICC1 protein boosts chemoresistance and stemness in pancreatic cancer by activating tryptophan metabolism. 🌟 Blocking BICC1/IDO1 pathways enhances gemcitabine effectiveness, offering a promising new target for treatment!

[sisiad]

WNT2–SOX4 positive feedback loop promotes chemoresistance and tumorigenesis by inducing stem-cell like properties in gastric cancer

http://dlvr.it/SvD5hQ

[cupcraft]

i just think its very super interesting how our microbiota can be another added piece to effectiveness and or ineffectiveness of cancer treatments. Like what do you mean this bacteria usually found in the oral microbiota can be found in high abundance in CRC and maybe contributes to chemoresistance or favorable tumor environments like whaatttt.

[rnomics]

IJMS, Vol. 25, Pages 3406: A Current Synopsis of the Emerging Role of Extracellular Vesicles and Micro-#RNAs in Pancreatic #cancer: A Forward-Looking Plan for Diagnosis and Treatment

Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest malignancies worldwide, while it persists as the fourth most prevalent cause of #cancer-related death in the United States of America. Although there are several novel therapeutic strategies for the approach of this intensely aggressive tumor, it remains a clinical challenge, as it is hard to identify in early stages, due to its asymptomatic course. A diagnosis is usually established when the disease is already in its late stages, while its chemoresistance constitutes an obstacle to the optimal management of this malignancy. The discovery of novel diagnostic and therapeutic tools is considered a necessity for this tumor, due to its low survival rates and treatment failures. One of the most extensively investigated potential diagnostic and therapeutic modalities is extracellular vesicles (EVs). These vesicles constitute nanosized double-lipid membraned particles that are characterized by a high heterogeneity that emerges from their distinct biogenesis route, their multi-variable sizes, and the particular cargoes that are embedded into these particles. Their pivotal role in cell-to-cell communication via their cargo and their implication in the pathophysiology of several diseases, including pancreatic #cancer, opens new horizons in the management of this malignancy. Meanwhile, the interplay between pancreatic carcinogenesis and short non-coding #RNA molecules (micro-#RNAs or miRs) is in the spotlight of current studies, as they can have either a role as tumor suppressors or promoters. The deregulation of both of the aforementioned molecules leads to several aberrations in the function of pancreatic cells, leading to carcinogenesis. In this review, we will explore the role of extracellular vesicles and #miRNAs in pancreatic #cancer, as well as their potent utilization as diagnostic and therapeutic tools. https://www.mdpi.com/1422-0067/25/6/3406?utm_source=dlvr.it&utm_medium=tumblr

[cytoscape-publications]

Combining Mass Spectrometry-Based Phosphoproteomics with a Network-Based Approach to Reveal FLT3-Dependent Mechanisms of Chemoresistance. Pugliese, et al., Proteomes doi: 10.3390/proteomes9020019.

Apps are available in the Cytoscape App Store.

[leedsomics]

Deep Quantitative Proteomics Identifies Conserved Proteome Alterations in Low and High-Grade Serous Ovarian Cancers

Low-grade serous ovarian carcinoma (LGSOC) is a rare and largely chemoresistant subtype of epithelial ovarian cancer. Unlike treatment for high-grade serous ovarian cancer (HGSOC), management options for LGSOC patients are limited, in part, due to a lack of deep molecular characterization of this disease. To address this limitation, we performed quantitative mass spectrometry-based proteomic analyses of whole tissue collections of tumors harvested from LGSOC (n=12) and HGSOC (n=24) patients or normal fallopian tube tissues (n=12) from women with benign disease. We quantified 7,043 proteins across all patient samples and unsupervised analyses revealed proteome alterations distinctly stratify fallopian tube tissue, LGSOC, and HGSOC tumors. Proteins elevated in LGSOC compared to HGSOC tumors (LIMMA adjusted p < 0.05) were enriched for pathways regulating cilium assembly and included a pathway regulating activation of FAK1 by MET, a therapeutic target in LGSOC. Using data from an independent proteomic analysis of LGSOC (n=14) and HGSOC (n=30) tumors, we identified 330 co-altered proteins between LGSOC and HGSOC tumors exhibiting high quantitative correlation (Spearman Rho = 0.803, P < 2.2E10-16). Among these, MUC16 was identified as significantly elevated (>1.7 log2-fold) in LGSOC versus HGSOC. Immunohistochemistry analysis of MUC16 verified the increased abundance in LGSOC tissues and identified that MUC16 staining patterns in LGSOC are uniquely apical compared to HGSOC (Fishers Exact p = 0.001). Our deep proteomic analyses identifies highly-conserved proteome alterations distinguishing LGSOC from HGSOC tumors, including candidates regulating FAK1 signaling as well as a novel identification that MUC16 is elevated and exhibits an apical staining pattern in LGSOC tumors. These findings deepen our molecular understanding of LGSOC and provide unique insights into the regulation of MUC16 in LGSOC tumors. http://dlvr.it/T6LtsP