The role of compartmentalized signaling pathways in the control of mitochondrial activities in cancer cells

Mitochondria are the powerhouse organelles present in all eukaryotic cells. They play a fundamental role in cell respiration, survival and metabolism. Stimulation of G-protein coupled receptors (GPCRs) by dedicated ligands and consequent activation of the cAMP·PKA pathway finely couple energy production and metabolism to cell growth and survival. Compartmentalization of PKA signaling at mitochondria by A-Kinase Anchor Proteins (AKAPs) ensures efficient transduction of signals generated at the cell membrane to the organelles, controlling important aspects of mitochondrial biology. Emerging evidence implicates mitochondria as essential bioenergetic elements of cancer cells that promote and support tumor growth and metastasis. In this context, mitochondria provide the building blocks for cellular organelles, cytoskeleton and membranes, and supply all the metabolic needs for the expansion and dissemination of actively replicating cancer cells. Functional interference with mitochondrial activity deeply impacts on cancer cell survival and proliferation. Therefore, mitochondria represent valuable targets of novel therapeutic approaches for the treatment of cancer patients. Understanding the biology of mitochondria, uncovering the molecular mechanisms regulating mitochondrial activity andmapping the relevant metabolic and signaling networks operating in cancer cells will undoubtly contribute to create a molecular platform to be used for the treatment of proliferative disorders. Here, we will highlight the emerging roles of signaling pathways acting downstream to GPCRs and their intersection with the ubiquitin proteasome system in the control of mitochondrial activity in different aspects of cancer cell biology

Small bowel infarction by Aspergillus.

Primary gut involvement by Aspergillus is a rare and often fatal complication of intensive antileukemic therapy. We describe the case of an adult patient affected by acute leukemia who developed a small bowel fungal thromboembolism without radiographic evidence of lung involvement during the post-induction aplastic phase. The diagnosis was made histologically at laparotomy performed for small bowel perforation. The patient died a week later in spite of amphotericin-B treatment and neutrophil recovery. Anti- Aspergillus prophylaxis and early introduction of amphotericin-B in the treatment of febrile neutropenia is probably advisable in all cases of AML

TCGA Molecular Subgroups in Endometrial Undifferentiated/Dedifferentiated Carcinoma

We aimed to classify undifferentiated/dedifferentiated carcinoma (UDC/DDC) according to the four TCGA molecular subgroups of endometrial cancer: microsatellite-instable/hypermutated (MSI), POLE-mutant/ultramutated (POLE), copy-number-low/p53-wild-type (p53wt), and copy-number-high/p53-abnormal (p53abn), through a systematic review and meta-analysis. Electronic databases were searched from January 2013 to July 2019 for studies assessing the TCGA classification in endometrial UDC/DDC series. Pooled prevalence of each TCGA subgroup on the total UDC/DDCs was calculated. Three studies with 73 patients were included. Pooled prevalence of the TCGA subgroups were: 12.4% for the POLE subgroup, 44% for the MSI subgroup, 18.6% for the p53abn subgroup, 25% for the p53wt group. All TCGA groups are represented in UDC/DDC, with a predominance of the MSI group, indicating a biological heterogeneity. Hypermutated/ultramutated cancers constitute the majority of UDC/DDC, suggesting a crucial difference with other high-risk histologies of endometrial carcinoma

Hashimoto Thyroiditis in Primary Thyroid Non-Hodgkin Lymphoma

OBJECTIVES: To assess the prevalence of Hashimoto thyroiditis (HT) in primary thyroid lymphoma (PTL) and whether it differs between mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBCL). METHODS: Electronic databases were searched for studies assessing HT prevalence in PTL, based on antithyroid antibodies, clinical history, or pathology. Pooled prevalence of HT and its association with histotype (MALT or DLBCL) were calculated. RESULTS: Thirty-eight studies with 1,346 PTLs were included. Pooled prevalence results were 78.9% (any HT evidence), 65.3% (antithyroid antibodies), 41.7% (clinical history), and 64% (pathology). HT prevalence was significantly higher in MALT lymphoma than in DLBCL (P = .007) and in mixed DLBCL/MALT than in pure DLBCL (P = .002). CONCLUSIONS: Overall, 78.9% of patients with PTL have any HT evidence, but only half of these had been clinically followed. The difference in HT prevalence suggests that a subset of DLBCL may not derive from MALT lymphoma

R0 surgical resection of giant dedifferentiated retroperitoneal liposarcomas in the COVID era with and without nephrectomy: A case report

: Retroperitoneal sarcomas (RPSs) are rare findings that can grow into large masses without eliciting severe symptoms. At present, surgical resection is the only radical therapy, whenever it can be performed with the aim to achieve a complete removal of the tumor. The present report describes two consecutive cases of RPSs that resulted in dedifferentiated liposarcomas (DDLPSs) and these patients underwent R0 surgical resection with and without a nephron-sparing procedure. The diagnostic workup, the surgical approach, the impact of late surgical management due to the COVID pandemic and the latest literature on the topic are discussed and analyzed. The patients, who refused to undergo any medical examination during the prior 2 years due to the COVID pandemic, were admitted to Federico II University Hospital (Naples, Italy) complaining about weight loss and general abdominal discomfort. In the first case, a primitive giant abdominal right neoplasm of retroperitoneal origin enveloping and medializing the right kidney was observed. The second patient had a similar primitive retroperitoneal giant left neoplasm, which did not affect the kidney. Given the characteristics of the masses and the absence of distant metastases, after a multidisciplinary discussion, radical surgical removal was carried out for both patients. The lesions appeared well-defined from the surrounding tissues, and markedly compressed all the adjacent organs, without signs of infiltration. In the first patient, the right kidney was surrounded and undetachable from the tumor and it was removed en bloc with the mass. The second patient benefited from a nephron-sparing resection, due to the existence of a clear cleavage plane. The postoperative courses were uneventful. Both the histological examinations were oriented towards a DDLPS and both patients benefited from adjuvant chemotherapy. In conclusion, the treatment of giant RPS is still challenging and requires multidisciplinary treatment as well as, when possible, radical surgical removal. The lack of tissue infiltration and the avoidance of excision or reconstruction of major organs (including the kidney) could lead to an easier postoperative course and an improved prognosis. When possible, surgical management of recurrences or incompletely resected masses must be pursued. Since the COVID pandemic caused limited medicalization of a number of population groups and delayed diagnosis of other oncologic diseases, an increased number of DDLPSs could be expected in the near future

Treatments and overall survival in patients with Krukenberg tumor

BACKGROUND: Krukenberg tumor (KT) is a rare secondary ovarian tumor, primarily localized at the gastrointestinal tract in most cases. KT is related to severe prognosis due to its aggressiveness, diagnostic difficulties and poor treatment efficacy. Several treatments have been used, such as cytoreductive surgery (CRS), adjuvant chemotherapy (CT) and/or hyperthermic intraperitoneal chemotherapy (HIPEC). To date, it is still unclear which treatment or combination of treatments is related to better survival. OBJECTIVE: To assess the most effective therapeutic protocol in terms of overall survival (OS). METHODS: A systematic review of the literature was performed by searching MEDLINE, Scopus, EMBASE, ClinicalTrial.gov, OVID, Web of Sciences, Cochrane Library, and Google Scholar for all studies assessing the association of treatments with OS in KTs. The effectiveness of each treatment protocol was evaluated by comparing the OS between patients treated with different treatment protocols. RESULTS: Twenty retrospective studies, with a total sample size of 1533 KTs, were included in the systematic review. Therapeutic protocols used were CRS in 18 studies, CT in 13 studies, HIPEC in 7 studies, neoadjuvant CT in 2 studies, and some combinations of these in 6 studies. Seven studies showed that CRS significantly improved OS compared to other treatments or association of treatments without it. 11 studies showed that CRS without residual (R0 CRS) had a significantly better OS than CRS with residual (R + CRS). Five studies showed that CT significantly improved OS, but other five showed it did not. Two studies showed that HIPEC in association with CRS improved OS, while another study showed that efficacy of HIPEC was comparable to CT. Two studies evaluated neoadjuvant CT, but results were conflicting. CONCLUSION: CRS and in particular R0 CRS are the treatments showing the clearest results in improving OS in KT patients. Results about CT are conflicting. HIPEC appears effective both alone and in combination with CRS, and also related to fewer adverse effect than CT. The usefulness of neoadjuvant CT is still unclear. The association of R0 CRS with HIPEC seems to be the most effective and safe therapeutic protocol for KT patients