Colon cancer in a 12-year-old girl with hypertriglyceridemia

Colorectal cancer is usually considered a disease of the elderly; however, in a small fraction of patients (2%-3% of all affected individuals), colorectal malignancies may develop earlier. The reasons whereby some individuals develop colorectal cancer at a young age are poorly understood. In a 12-year-old girl, a malignancy was diagnosed in the ascending colon. There was no familial history of Lynch syndrome or familial adenomatous polyposis. The metabolic profile of the patient revealed hypertriglyceridemia and low high-density lipoprotein cholesterol levels at nine years, then diagnosed as familial hypertriglyceridemia due to a constitutional mutation in the APOA5 gene (c.427delC). Moreover, variants possibly increasing the risk of cancer were detected in MSH6 (c.3438+11_3438+14delCTTA, intron 5) and APC (I1307K). The patient showed a rather unusual dietary pattern, since her basic alimentation from weaning consisted almost exclusively of meat homogenates and, subsequently, roasted meat or cutlets. Other foods, including fish, vegetables, sweets, and pasta, were refused. In this case, genetic and environmental factors could have acted in a particularly accelerated manner. Indeed, the genetic background of the patient (familial hypertriglyceridemia and polymorphisms predisposing to colorectal cancer) may have favored a dietary-driven colorectal carcinogenesis, resulting in an extremely early onset development of malignancy

Argyrophilic nucleolar organizer regions and bromodeoxyuridine and h3-thymidine labelling indices in colorectal cancer

The count of argyrophilic nucleolar organizer regions (AgNORs) has been proposed as a useful method for evaluating cell replication in human tumours. The current study was undertaken to compare AgNOR values in colorectal cancers with two better established methods for investigating cell proliferation such as bromodeoxyuridine (BrdUrd) and (3)[H]-thymidine ((3)[H]dT) labelling indices (LIs). Because some concern still exists regarding accuracy and reproducibility of AgNOR quantifying methods, we carried out a control study by independently repeating the same measurements (number, area and area per silver-stained NOR particle) in two centres with different operators and computer-assisted image analysers on 40 colorectal carcinomas. AgNOR values recorded in the two centres were strictly correlated (r = 0.75; P < 0.001 for number; r = 0.62, P < 0.01 for area; r = 0.63, P < 0.001 for area per silver-stained NOR particle) and the range of values were almost identical, Then, AgNOR values were compared with BrdUrd and (3)[H]dT LIs, respectively obtained by in vivo incorporation and in vitro incubation in the same series of colorectal carcinomas. No correlation was found between AgNOR values and BrdUrd or (3)[H]dT LIs. BrdUrd and (3)[H]dT LIs were instead reciprocally significantly correlated, No evident correlation was seen between LIs or AgNOR values and clinico-pathological parameters of the tumour. In conclusion, in colorectal neoplasms, AgNOR values did not appear to relate with more direct parameters of cell proliferation. It follows that AgNOR reliability as a biomarker of cell proliferation remains questionable

Repurposing of plasminogen: An orphan medicinal product suitable for SARS-CoV-2 inhalable therapeutics

The SARS-CoV-2 infection is associated with pulmonary coagulopathy, which determines the deposition of fibrin in the air spaces and lung parenchyma. The resulting lung lesions compromise patient pulmonary function and increase mortality, or end in permanent lung damage for those who have recovered from the COVID-19 disease. Therefore, local pulmonary fibrinolysis can be efficacious in degrading pre-existing fibrin clots and reducing the conversion of lung lesions into lasting scars. Plasminogen is considered a key player in fibrinolysis processes, and in view of a bench-to-bedside translation, we focused on the aerosolization of an orphan medicinal product (OMP) for ligneous conjunctivitis: human plasminogen (PLG-OMP) eye drops. As such, the sterile and preservative-free solution guarantees the pharmaceutical quality of GMP production and meets the Ph. Eur. requirements of liquid preparations for nebulization. PLG-OMP aerosolization was evaluated both from technological and stability viewpoints, after being submitted to either jet or ultrasonic nebulization. Jet nebulization resulted in a more efficient delivery of an aerosol suitable for pulmonary deposition. The biochemical investigation highlighted substantial protein integrity maintenance with the percentage of native plasminogen band > 90%, in accordance with the quality specifications of PLG-OMP. In a coherent way, the specific activity of plasminogen is maintained within the range 4.8–5.6 IU/mg (PLG-OMP pre-nebulization: 5.0 IU/mg). This is the first study that focuses on the technological and biochemical aspects of aerosolized plasminogen, which could affect both treatment efficacy and clinical dosage delivery. Increasing evidence for the need of local fibrinolytic therapy could merge with the availability of PLG-OMP as an easy handling solution, readily aerosolizable for a fast translation into an extended clinical efficacy assessment in COVID-19 patients

Computer-aided design/computer-aided manufacturing of hydroxyapatite scaffolds for bone reconstruction in jawbone atrophy: a systematic review and case report.

BACKGROUND: We reviewed the biological and mechanical properties of porous hydroxyapatite (HA) compared to other synthetic materials. Computer-aided design/computer-aided manufacturing (CAD/CAM) was also evaluated to estimate its efficacy with clinical and radiological assessments. METHOD: A systematic search of the electronic literature database of the National Library of Medicine (PubMed-MEDLINE) was performed for articles published in English between January 1985 and September 2013. The inclusion criteria were (1) histological evaluation of the biocompatibility and osteoconductivity of porous HA in vivo and in vitro, (2) evaluation of the mechanical properties of HA in relation to its porosity, (3) comparison of the biological and mechanical properties between several biomaterials, and (4) clinical and radiological evaluation of the precision of CAD/CAM techniques. RESULTS: HA had excellent osteoconductivity and biocompatibility in vitro and in vivo compared to other biomaterials. HA grafts are suitable for milling and finishing, depending on the design. In computed tomography, porous HA is a more resorbable and more osteoconductive material than dense HA; however, its strength decreases exponentially with an increase in porosity. CONCLUSIONS: Mechanical tests showed that HA scaffolds with pore diameters ranging from 400 to 1200 \u3bcm had compressive moduli and strength within the range of the human craniofacial trabecular bone. In conclusion, using CAD/CAM techniques for preparing HA scaffolds may increase graft stability and reduce surgical operating time

Th Inducing POZ-Kruppel Factor (ThPOK) Is a Key Regulator of the Immune Response since the Early Steps of Colorectal Carcinogenesis

We purposed to evaluate the role of Th inducing POZ-Kruppel Factor (ThPOK), a transcriptional regulator of T cell fate, in tumour-induced immune system plasticity in colorectal carcinogenesis. The amounts of CD4+, CD8+ and CD56+ and ThPOK+ cells infiltrate in normal colorectal mucosa (NM), in dysplastic aberrant crypt foci (microadenomas, MA), the earliest detectable lesions in colorectal carcinogenesis, and in colorectal carcinomas (CRC), were measured, and the colocalization of ThPOK with the above-mentioned markers of immune cells was evaluated using confocal microscopy. Interestingly, ThPOK showed a prominent increase since MA. A strong colocalization of ThPOK with CD4 both in NM and in MA was observed, weaker in carcinomas. Surprisingly, there was a peak in the colocalization levels of ThPOK with CD8 in MA, which was evident, although to a lesser extent, in carcinomas, too. In conclusion, according to the data of the present study, ThPOK may be considered a central regulator of the earliest events in the immune system during colorectal cancer development, decreasing the immune response against cancer cells

Expression of neutrophil gelatinase-associated lipocalin in colorectal neoplastic progression:A marker of malignant potential?

Peer reviewedPublisher PD

Low tumour cell proliferation at the invasive margin is associated with a poor prognosis in Dukes' stage B colorectal cancers

The conflicting results about the prognostic impact of tumour cell proliferation in colorectal cancer might be explained by the heterogeneity observed within these tumours. We have investigated whether a systematic spatial heterogeneity exists between different compartments, and whether the presence of such a systematic heterogeneity has any impact on survival. Fifty-six Dukes' stage B colorectal cancers were carefully morphometrically quantified with respect to the immunohistochemical expression of the proliferative marker Ki-67 at both the luminal border and the invasive margin. The proliferative activity was significantly higher at the luminal border compared with the invasive margin (P < 0.001), although the two compartments were also significantly correlated with each other. Tumours with low proliferation at the invasive margin had a significantly poorer prognosis both in univariate (P = 0.014) and in multivariate survival analyses (P = 0.042). We conclude that Dukes' B colorectal cancers exhibit a systematic spatial heterogeneity with respect to proliferation, and tumours with low proliferation at the invasive margin had a poor prognosis. The present data independently confirm recent results from the authors, and provide new insights into the understanding of tumour cell proliferation in colorectal cancer. © 1999 Cancer Research Campaig

Alkylation of the Tumor Suppressor PTEN Activates Akt and β-Catenin Signaling: A Mechanism Linking Inflammation and Oxidative Stress with Cancer

PTEN, a phosphoinositide-3-phosphatase, serves dual roles as a tumor suppressor and regulator of cellular anabolic/catabolic metabolism. Adaptation of a redox-sensitive cysteinyl thiol in PTEN for signal transduction by hydrogen peroxide may have superimposed a vulnerability to other mediators of oxidative stress and inflammation, especially reactive carbonyl species, which are commonly occurring by-products of arachidonic acid peroxidation. Using MCF7 and HEK-293 cells, we report that several reactive aldehydes and ketones, e.g. electrophilic α,β-enals (acrolein, 4-hydroxy-2-nonenal) and α,β-enones (prostaglandin A2, Δ12-prostaglandin J2 and 15-deoxy-Δ-12,14-prostaglandin J2) covalently modify and inactivate cellular PTEN, with ensuing activation of PKB/Akt kinase; phosphorylation of Akt substrates; increased cell proliferation; and increased nuclear β-catenin signaling. Alkylation of PTEN by α,β-enals/enones and interference with its restraint of cellular PKB/Akt signaling may accentuate hyperplastic and neoplastic disorders associated with chronic inflammation, oxidative stress, or aging