Mesenchymal stem cells-derived secretome and extracellular vesicles: perspective and challenges in cancer therapy and clinical applications.

Stem cell-based therapies have been foreshowed as a promising therapeutic approach for the treatment of several diseases. However, in the cancer context, results obtained from clinical studies were found to be quite limited. Deeply implicated in inflammatory cues, Mesenchymal, Neural, and Embryonic Stem Cells have mainly been used in clinical trials as a vehicle to deliver and stimulate signals in tumors niche. Although these stem cells have shown some therapeutical promises, they still face several challenges, including their isolation, immunosuppression potential, and tumorigenicity. In addition, regulatory and ethical concerns limit their use in several countries. Mesenchymal stem cells (MSC) have emerged as a gold standard adult stem cell medicine tool due to their distinctive characteristics, such as self-renewal and potency to differentiate into numerous cell types with lower ethical restrictions. Secreted extracellular vesicles (EVs), secretomes, and exosomes play a crucial role in mediating cell-to-cell communication to maintain physiological homeostasis and influence pathogenesis. Due to their low immunogenicity, biodegradability, low toxicity, and ability to transfer bioactive cargoes across biological barriers, EVs and exosomes were considered an alternative to stem cell therapy through their immunological features. MSCs-derived EVs, exosomes, and secretomes showed regenerative, anti-inflammatory, and immunomodulation properties while treating human diseases. In this review, we provide an overview of the paradigm of MSCs derived exosomes, secretome, and EVs cell-free-based therapies, we will focus on MSCs-derived components in anti-cancer treatment with decreased risk of immunogenicity and toxicity. Astute exploration of MSCs may lead to a new opportunity for efficient therapy for patients with cancer.

Post-COVID-19 Secondary Sclerosing Cholangitis: A Rare but Severe Condition with no Treatment Besides Liver Transplantation.

BACKGROUND The incidence of abnormal liver function, mainly aspartate aminotransferase and alanine aminotransferase elevations, in patients with COVID-19 is not uncommon, but persistent liver damage after the acute phase of the disease is uncommon and has been recently recognized as a new entity named post-COVID-19 cholangiopathy. CASE REPORT We report a clinical case with progressive cholestatic disease following severe COVID-19. AST and ALT peaked at hospital admission and while its serum concentration went down, bilirubin and cholestatic liver enzymes started to increase, reaching the maximum at day 122. Magnetic resonance imaging (MRI) revealed a diffuse irregularity of intra- and extrahepatic bile ducts, with multiple focal strictures alternating with mild focal dilations of the biliary tree, suggesting a sclerosing cholangiopathy. A transjugular liver biopsy showed a prominent bile ductular reaction, cholangiocyte injury, inflammatory infiltrate rich in neutrophils, biliary infarctions, marked cholestasis, and portal fibrosis, suggesting the diagnosis of post-Covid-19 secondary sclerosing cholangitis. The patient evolved with a continuous deterioration of liver functions, but liver transplantation was not performed due to his poor clinical condition. CONCLUSIONS Post-COVID-19 SSC is a severe disease with no effective clinical treatment and has liver transplantation as the only treatment for a few selected patients.

A second reported malignancy in a patient with Morquio syndrome.

Morquio syndrome is a rare lysosomal storage disease that affects multiple organ systems. However, it is rarely associated with malignancy. We present the case of a 30-year old man with Morquio syndrome associated with gastric adenocarcinoma. This case also demonstrates two other findings that have not been previously described in patients with Morquio syndrome - malrotation of brainstem and cerebellum, without clinical neurologic deficit, and persistence of fetal lobulation in the kidneys.

A second reported malignancy in a patient with Morquio syndrome

Morquio syndrome is a rare lysosomal storage disease that affects multiple organ systems. However, it is rarely associated with malignancy. We present the case of a 30-year old man with Morquio syndrome associated with gastric adenocarcinoma. This case also demonstrates two other findings that have not been previously described in patients with Morquio syndrome - malrotation of brainstem and cerebellum, without clinical neurologic deficit, and persistence of fetal lobulation in the kidneys.

Decision making and factors influencing long-term satisfaction with prophylactic mastectomy in women with breast cancer.

PURPOSE: Studies demonstrate an increasing rate of contralateral prophylactic mastectomy (CPM). The purpose of this study is to evaluate decision making and factors influencing women's long-term satisfaction with CPM. Descriptive analysis is used to analyze the results of our designed questionnaire approved by our Institutional Review Board. METHODS: We searched our institutional cancer registry for patients diagnosed with breast cancer between 2000 and 2010. The studied time frame is of significance as this study is the first to measure response rate in questions examining patient satisfaction for >1 year after undergoing CPM. The questionnaire was mailed to all consented participants to examine factors contributing to the choice of CPM and postoperative satisfaction. RESULTS: Of the 206 women included in the study, 147 were aged up to 50 years. Majority of women who underwent CPM in this cohort was with a bachelor's degree or higher, married or partnered women, and women earning >$60,000/y. Almost all women were "happy with overall surgery" and would recommend CPM to other patients. Psychological factors, such as fear of recurrence, were more commonly associated with the decision for CPM in patients with invasive carcinoma. Opinions of partners, relatives, friends, and physicians further contributed to the decision to undergo surgery. The availability of reconstruction was also an influential factor in the overall decision. CONCLUSIONS: The majority of our study participants experienced long-term satisfaction with the surgical procedure of CPM. From our analysis, we can confidently say that fear of cancer recurrence and the opinions of others, among other factors, were influencing contributors toward the decision of undergoing CPM.