Oncogenic KRAS mutations modulate BAX-mediated cell death.

Kirsten rat sarcoma viral oncogene homolog (KRAS) belongs to the GTPase RAS superfamily, which regulates several cell-signaling pathways involved in the control of important cellular functions, including apoptosis. Oncogenic mutations in KRAS are considered the most common gain-of-function mutations, affecting 30-50 % of colorectal cancer (CRC) patients. While RAS proteins usually play an anti-apoptotic role, little is known about the involvement of KRAS mutations in apoptosis regulation.

Anticancer Activity of Benzo[]phenoxazine Compounds Promoting Lysosomal Dysfunction.

Specific cancer therapy remains a problem to be solved. Breast and colorectal cancer are among the cancers with the highest prevalence and mortality rates. Although there are some therapeutic options, there are still few effective agents for those cancers, which constitutes a clinical problem that requires further research efforts.

Enhancement of Acetate-Induced Apoptosis of Colorectal Cancer Cells by Cathepsin D Inhibition Depends on Oligomycin A-Sensitive Respiration.

Colorectal cancer (CRC) is a leading cause of death worldwide. Conventional therapies are available with varying effectiveness. Acetate, a short-chain fatty acid produced by human intestinal bacteria, triggers mitochondria-mediated apoptosis preferentially in CRC but not in normal colonocytes, which has spurred an interest in its use for CRC prevention/therapy.

New Ruthenium-Cyclopentadienyl Complexes Affect Colorectal Cancer Hallmarks Showing High Therapeutic Potential.

Colorectal cancer (CRC) is among the most deadly cancers worldwide. Current therapeutic strategies have low success rates and several side effects. This relevant clinical problem requires the discovery of new and more effective therapeutic alternatives.

Modulation of the Tumor Microenvironment by Microbiota-Derived Short-Chain Fatty Acids: Impact in Colorectal Cancer Therapy.

Finding new therapeutic approaches towards colorectal cancer (CRC) is of increased relevance, as CRC is one of the most common cancers worldwide. CRC standard therapy includes surgery, chemotherapy, and radiotherapy, which may be used alone or in combination. The reported side effects and acquired resistance associated with these strategies lead to an increasing need to search for new therapies with better efficacy and less toxicity.

Targeting Lysosomes in Colorectal Cancer: Exploring the Anticancer Activity of a New Benzo[]phenoxazine Derivative.

Colorectal cancer (CRC) has been ranked as one of the cancer types with a higher incidence and one of the most mortal. There are limited therapies available for CRC, which urges the finding of intracellular targets and the discovery of new drugs for innovative therapeutic approaches. In addition to the limited number of effective anticancer agents approved for use in humans, CRC resistance and secondary effects stemming from classical chemotherapy remain a major clinical problem, reinforcing the need for the development of novel drugs.

Microbiota-Derived Short-Chain Fatty Acids: New Road in Colorectal Cancer Therapy.

The colon microbiota is an important player in colorectal cancer (CRC) development, which is responsible for most of the cancer-related deaths worldwide. During carcinogenesis, the colon microbiota composition changes from a normobiosis profile to dysbiosis, interfering with the production of short-chain fatty acids (SCFAs). Each SCFA is known to play a role in several biological processes but, despite their reported individual effects, colon cells are exposed to these compounds simultaneously and the combined effect of SCFAs in colon cells is still unknown.

Colon microbiota modulation by dairy-derived diet: new strategy for prevention and treatment of colorectal cancer.

An unbalanced diet is one of the well-known risk factors for the development of colorectal cancer (CRC). This type of cancer is currently the main cause of cancer-related deaths worldwide, urging the need for new and more effective preventive and therapeutic approaches. It is already known that CRC patients have alterations in the microbial community and metabolism.

Biotinylated Polymer-Ruthenium Conjugates: In Vitro and In Vivo Studies in a Triple-Negative Breast Cancer Model.

The need for new therapeutic approaches for triple-negative breast cancer is a clinically relevant problem that needs to be solved. Using a multi-targeting approach to enhance cancer cell uptake, we synthesized a new family of ruthenium(II) organometallic complexes envisaging simultaneous active and passive targeting, using biotin and polylactide (PLA), respectively. All compounds with the general formula, [Ru(η-CpR)(P)(2,2'-bipy-4,4'-PLA-biotin)][CFSO], where R is -H or -CH and P is P(CH), P(CHF) or P(CHOCH), were tested against triple-negative breast cancer cells MDA-MB-231 showing IC values between 2.

Crucial Role of Oncogenic Mutations in Apoptosis and Autophagy Regulation: Therapeutic Implications.

KRAS, one of the RAS protein family members, plays an important role in autophagy and apoptosis, through the regulation of several downstream effectors. In cancer cells, mutations confer the constitutive activation of this oncogene, stimulating cell proliferation, inducing autophagy, suppressing apoptosis, altering cell metabolism, changing cell motility and invasion and modulating the tumor microenvironment. In order to inhibit apoptosis, these oncogenic mutations were reported to upregulate anti-apoptotic proteins, including Bcl-xL and survivin, and to downregulate proteins related to apoptosis induction, including thymine-DNA glycosylase (TDG) and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL).

Ruthenium(II)-Cyclopentadienyl-Derived Complexes as New Emerging Anti-Colorectal Cancer Drugs.

Colorectal cancer (CRC) is one of the most common malignancies and one of the leading causes of cancer-related death worldwide, urging the need for new and more efficient therapeutic approaches. Ruthenium complexes have emerged as attractive alternatives to traditional platinum-based compounds in the treatment of CRC. This work aims to evaluate anti-CRC properties, as well as to identify the mechanisms of action of ruthenium complexes with the general formula [Ru(η-CHR)(PPh)(4,4'-R'-2,2'-bipyridine)][CFSO], where R = CH, CHO or CHOH and R' = H, CH, CHOH, or dibiotin ester.

KRAS as a Modulator of the Inflammatory Tumor Microenvironment: Therapeutic Implications.

mutations are one of the most frequent oncogenic mutations of all human cancers, being more prevalent in pancreatic, colorectal, and lung cancers. Intensive efforts have been encouraged in order to understand the effect of mutations, not only on tumor cells but also on the dynamic network composed by the tumor microenvironment (TME). The relevance of the TME in cancer biology has been increasing due to its impact on the modulation of cancer cell activities, which can dictate the success of tumor progression.

Novel Nile Blue Analogue Stains Yeast Vacuolar Membrane, Endoplasmic Reticulum, and Lipid Droplets, Inducing Cell Death through Vacuole Membrane Permeabilization.

Phenoxazine derivatives such as Nile Blue analogues are assumed to be increasingly relevant in cell biology due to their fluorescence staining capabilities and antifungal and anticancer activities. However, the mechanisms underlying their effects remain poorly elucidated. Using as a eukaryotic model, we found that BaP1, a novel 5- and 9--substituted benzo[]phenoxazine synthesized in our laboratory, when used in low concentrations, accumulates and stains the vacuolar membrane and the endoplasmic reticulum.

Growing Teratoma Syndrome: A Rare Outcome.

Growing teratoma syndrome is a rare condition described in both testicular and ovarian cancer. We present a case of a 26-year-old male with known mixed germ cell tumor which exhibited new and progressive secondary lesions during imaging surveillance, later to be histologically characterized as teratomas.

Gastric metastases from invasive lobular carcinoma of the breast: Case report.

Invasive lobular carcinoma is the second most common type of invasive carcinoma of the breast. Although rare, invasive lobular carcinoma can lead to gastric metastases, which may appear several years after the initial diagnosis. The diagnosis is difficult, either because of its rarity or because of overlapping symptoms and imaging findings with primary gastric carcinoma.

A New Family of Iron(II)-Cyclopentadienyl Compounds Shows Strong Activity Against Colorectal and Triple Negative Breast Cancer Cells.

A family of compounds with the general formula [Fe(η-CH)(CO)(PPh)(NCR)] has been synthesized (NCR = benzonitrile (); 4-hydroxybenzonitrile (); 4-hydroxymethylbenzonitrile (); 4-aminobenzonitrile (); 4-bromobenzonitrile (); and, 4-chlorocinnamonitrile ()). All of the compounds were obtained in good yields and were completely characterized by standard spectroscopic and analytical techniques. Compounds , , and crystallize in the monoclinc P21/c space group and packing is determined by short contacts between the phosphane phenyl rings and cyclopentadienyl (compounds and ) or π-π lateral interactions between the benzonitrile molecules (complex ).

Ruthenium-Cyclopentadienyl Bipyridine-Biotin Based Compounds: Synthesis and Biological Effect.

Prospective anticancer metallodrugs should consider target-specific components in their design in order to overcome the limitations of the current chemotherapeutics. The inclusion of vitamins, which receptors are overexpressed in many cancer cell lines, has proven to be a valid strategy. Therefore, in this paper we report the synthesis and characterization of a set of new compounds [Ru(η-CH)(P(CHR))(4,4'-R'-2,2'-bpy)] (R = F and R' = H, ; R = F and R' = biotin, ; R = OCH and R' = H, ; R = OCH and R' = biotin, ), inspired by the exceptional good results recently obtained for the analogue bearing a triphenylphosphane ligand.

MCT1, MCT4 and CD147 expression and 3-bromopyruvate toxicity in colorectal cancer cells are modulated by the extracellular conditions.

Monocarboxylate transporters (MCTs) inhibition leads to disruption in glycolysis, induces cell death and decreases cell invasion, revealing the importance of MCT activity in intracellular pH homeostasis and tumor aggressiveness. 3-Bromopyruvate (3BP) is an anti-tumor agent, whose uptake occurs via MCTs. It was the aim of this work to unravel the importance of extracellular conditions on the regulation of MCTs and in 3BP activity.

Ultrasound elastography: compression elastography and shear-wave elastography in the assessment of tendon injury.

Ultrasound elastography (USE) is a recent technology that has experienced major developments in the past two decades. The assessment of the main mechanical properties of tissues can be made with this technology by characterisation of their response to stress. This article reviews the two major techniques used in musculoskeletal elastography, compression elastography (CE) and shear-wave elastography (SWE), and evaluates the studies published on major electronic databases that use both techniques in the context of tendon pathology.

Colorectal Cancer Cells Increase the Production of Short Chain Fatty Acids by Impacting on Cancer Cells Survival.

is a commercially relevant bacterium with probiotic potential. This bacterium can exert protective effects particularly against colorectal cancer (CRC), via the production of short chain fatty acids (SCFA), namely acetate and propionate. In this work, we aimed to evaluate the performance and adaptation capacity of to a simulated digestive stress using different culture media, namely YEL, Basal medium, Mimicking the Content of the Human Colon medium (MCHC) and DMEM.

The Role of Diet Related Short-Chain Fatty Acids in Colorectal Cancer Metabolism and Survival: Prevention and Therapeutic Implications.

Colorectal Cancer (CRC) is a major cause of cancer-related death worldwide. CRC increased risk has been associated with alterations in the intestinal microbiota, with decreased production of Short Chain Fatty Acids (SCFAs). SCFAs produced in the human colon are the major products of bacterial fermentation of undigested dietary fiber and starch.

Small bowel intussusception in 2 adults caused by inflammatory polyps.

Inflammatory fibroid polyps are rare, benign pseudotumors of the gastrointestinal tract of unknown etiology, which may rarely present as bowel intussusception and obstruction. The authors describe the clinical, radiologic, and pathologic features of 2 patients with ileal inflammatory fibroid polyps presenting as small bowel intussusception.

The Yeast Saccharomyces cerevisiae as a Model for Understanding RAS Proteins and their Role in Human Tumorigenesis.

The exploitation of the yeast as a biological model for the investigation of complex molecular processes conserved in multicellular organisms, such as humans, has allowed fundamental biological discoveries. When comparing yeast and human proteins, it is clear that both amino acid sequences and protein functions are often very well conserved. One example of the high degree of conservation between human and yeast proteins is highlighted by the members of the RAS family.