411 research outputs found
Toxins and Cancer Therapy
No full textCancer has been a patient-specific and difficult-to-treat disease for decades, resulting in more deaths since 1900 than all other diseases except cardiovascular diseases. As societies around the world continue to shift towards an aging population, the social and economic burden created by cancer will only rise in the coming decades, necessitating continued improvement in our cancer therapies. Remarkably, in the late 1800s, bone surgeon William Coley serendipitously discovered that bacteria could be administered to patients as an effective (and sometimes toxic) form of cancer therapy known as "Coley's Toxins". His discoveries unknowingly led to two fields of cancer therapy that have been in development for decades and are now leading to significant improvements in therapy for cancer patients: immune-based and toxin-based therapies for cancer. Articles included here discuss the discoveries that emerged from Coley's Toxins that enable us to harness the immune system and microbial toxins to combat cancers, as oncology shifts from a field dominated by chemotherapy for most of the 20th century to biologic therapies that will dominate the 21st century
Toxins and Cancer Therapy
No full textCancer has been a patient-specific and difficult-to-treat disease for decades, resulting in more deaths since 1900 than all other diseases except cardiovascular diseases. As societies around the world continue to shift towards an aging population, the social and economic burden created by cancer will only rise in the coming decades, necessitating continued improvement in our cancer therapies. Remarkably, in the late 1800s, bone surgeon William Coley serendipitously discovered that bacteria could be administered to patients as an effective (and sometimes toxic) form of cancer therapy known as "Coley's Toxins". His discoveries unknowingly led to two fields of cancer therapy that have been in development for decades and are now leading to significant improvements in therapy for cancer patients: immune-based and toxin-based therapies for cancer. Articles included here discuss the discoveries that emerged from Coley's Toxins that enable us to harness the immune system and microbial toxins to combat cancers, as oncology shifts from a field dominated by chemotherapy for most of the 20th century to biologic therapies that will dominate the 21st century
Linkage analysis in cases of serial burglary : comparing the performance of university students, police professionals, and a logistic regression model
No full textUniversity students, police professionals, and a logistic regression model were provided with information on 38 pairs of burglaries, 20% of which were committed by the same offender, in order to examine their ability to accurately identify linked serial burglaries. For each offense pair, the information included: (1) the offense locations as points on a map, (2) the distance (in km) between the two offenses, (3) entry methods, (4) target characteristics, and (5) property stolen. Half of the participants received training informing them that the likelihood of two offenses being committed by the same offender increases as the distance between the offenses decreases. Results showed that students outperformed police professionals, that training increased decision accuracy, and that the logistic regression model achieved the highest rate of success. Potential explanations for these results are presented, focusing primarily on the participants' use of offense information, and their implications are discussed
ST-Producing E. coli Oppose Carcinogen-Induced Colorectal Tumorigenesis in Mice
No full textThere is a geographic inequality in the incidence of colorectal cancer, lowest in developing countries, and greatest in developed countries. This disparity suggests an environmental contribution to cancer resistance in endemic populations. Enterotoxigenic bacteria associated with diarrheal disease are prevalent in developing countries, including enterotoxigenic E. coli (ETEC) producing heat-stable enterotoxins (STs). STs are peptides that are structurally homologous to paracrine hormones that regulate the intestinal guanylyl cyclase C (GUCY2C) receptor. Beyond secretion, GUCY2C is a tumor suppressor universally silenced by loss of expression of its paracrine hormone during carcinogenesis. Thus, the geographic imbalance in colorectal cancer, in part, may reflect chronic exposure to ST-producing organisms that restore GUCY2C signaling silenced by hormone loss during transformation. Here, mice colonized for 18 weeks with control E. coli or those engineered to secrete ST exhibited normal growth, with comparable weight gain and normal stool water content, without evidence of secretory diarrhea. Enterotoxin-producing, but not control, E. coli, generated ST that activated colonic GUCY2C signaling, cyclic guanosine monophosphate (cGMP) production, and cGMP-dependent protein phosphorylation in colonized mice. Moreover, mice colonized with ST-producing E. coli exhibited a 50% reduction in carcinogen-induced colorectal tumor burden. Thus, chronic colonization with ETEC producing ST could contribute to endemic cancer resistance in developing countries, reinforcing a novel paradigm of colorectal cancer chemoprevention with oral GUCY2C-targeted agents
The Presence of GC-C in Extracellular Vesicles Secreted by Colorectal Cancer Cells
No full textBackground: Guanylyl Cyclase C (GC-C) is a membrane-bound protein found on intestinal epithelial cells involved in the activation of CFTR. This protein has previously been involved in the development of colorectal cancer.
Extracellular vesicles (EVs) are bilayered vesicles of varying size (30 to 1,000 + nm in diameter) that believed to be secreted by all cells in the human body. In the past decade, EVs have garnered attention due to their impact in the field of oncology, where they have been shown to potentially serve as biomarkers for various cancers.
In this study, we looked at the EVs secreted by GC-C+ and GC-C- cell lines. We expected GC-C to be present on the EVs secreted by GC-C+ cell lines and that this finding may intake a role for GC-C at tissues distal to the intestinal epithelial cells.
Methods: GC-C+ cells lines (T84 and CT26-hGCC) and GC-C- cell lines (SW480 and CT26-WT) were cultured and their media was harvested, then ultracentrifuged to extract the EVs from the media. These EVs were then checked for the presence and absence of various markers (GC-C, Calnexin, TSG101) via Western Blot. Exosome size was assessed via NTA to further provide evidence for the identity of these EVs.
Results: Western blot confirmed the presence of TSG101 in both EV types samples, as well as the presence of GC-C in EVs derived from GC-C+ cell lines, but not from GC-C- cell lines. Calnexin was found to be absent in EV samples, excluding the possibility of lysate contamination. NTA analysis confirmed the correct size for the exosomes in sample.
Discussion: This study assessed the contents of EVs secreted by colorectal cancer cell lines. Our findings indicate the presence of GC-C on exosomes and microvesicles. Further studies will need to be conducted in order to assess the function of these GC-C+ EVs in the setting of colorectal cancer
Listeria monocytogenes as a Vector for Cancer Immunotherapy: Current Understanding and Progress
No full textListeria monocytogenes, a Gram-positive facultative anaerobic bacterium, is becoming a popular vector for cancer immunotherapy. Indeed, multiple vaccines have been developed utilizing modified Listeria as a tool for generating immune responses against a variety of cancers. Moreover, over a dozen clinical trials testing Listeria cancer vaccines are currently underway, which will help to understand the utility of Listeria vaccines in cancer immunotherapy. This review aims to summarize current views on how Listeria-based vaccines induce potent antitumor immunity and the current state of Listeria-based cancer vaccines in clinical trials
Immunotherapy regimens for metastatic colorectal carcinomas
No full textMetastatic colorectal cancer (mCRC) is a leading cause of cancer-related mortality with a 5-year overall survival rate of 13%. Despite recent advances in cancer immunotherapy, only the minority of CRC patients (<15%) with microsatellite instability can potentially benefit from immune checkpoint inhibitors, the only immunotherapy currently approved for mCRC. In that context, there is an unmet need to improve survival in mCRC. Our ever-increasing understanding of the immune system and its interactions with cancer has allowed development of multiple strategies to potentially improve outcomes in the majority of mCRC patients. Various approaches to manipulate patient immunity to recognize and kill colorectal cancer cells are being explored simultaneously, with combination therapies likely being the most effective. Ideally, therapies would target tumor-restricted antigens selectively found in tumors, but shielded from immune attack in normal tissues, to mount an effective cytotoxic T-cell response, while also overcoming cellular and molecular inhibitory pathways, self-tolerance, and T-cell exhaustion. Here, we provide a brief overview of the most promising immunotherapy candidates in mCRC and their strategies to produce a lasting immune response and clinical benefit in patients with mCRC
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