Tailored treatment for signet ring cell gastric cancer

Gastric cancer with Laur\ue8n diffuse types is increasing in the West. The raising trend is more evident when considering signet ring cells (SRC) histology. However, to control the biologic potential of this GC subtype, some hypotheses of tailored therapeutic strategies for SRC cancers have been made. A review of the literature was performed using the key words "signet ring cells" AND "gastric cancer". Results of literature review were descriptively reported. Endoscopic submucosal dissection (ESD), according to the Japanese extended criteria, could be a therapeutic option for early SRC tumours. However, according to the evidences from more recent studies, indications for ESD to these tumours types should be carefully considered. Concerning the optimal surgical treatment, considering the high lymphotropism and infiltrating behaviour of SRC histotype, the extension of gastric resection should be wider than for intestinal type cancer and laparoscopic surgery should be performed carefully. Moreover, D3 lymphadenectomy could provide a benefit in diffuse-type and SRC histology. The role of surgery in gastric cancer with peritoneal carcinomatosis is still debated and studies on this topic should stratify the good results according to GC histotype. Finally, despite the evidences of chemoresistance in SRC, ongoing randomized trials suggest that multimodal therapy could be the best treatment. Based on the assumption that SRC tumours have specific features, they deserve a specific multimodal treatment. However, a preliminary step to generate strong evidences in this field is the standardization of terminology used to define signet ring cells carcinoma

Preliminary analyses of changes in intense precipitation in FVG, northeastern Italy

oai:air.uniud.it:11390/126739

Filamin A in somatostatin and dopamine receptor regulation in pituitary and the role of cAMP/PKA dependent phosphorylation

Molecular mechanisms underlying resistance of pituitary tumors to somatostatin (SS) and dopamine (DA) analogues treatment are not completely understood. Resistance has been associated with defective expression of functional somatostatin and dopamine receptors SSTR2, SSTR5, and DRD2, respectively. Recently, a role of cytoskeleton protein filamin A (FLNA) in DRD2 and SSTR receptors expression and signaling in PRL- and GH-secreting tumors, respectively, has been demonstrated, first revealing a link between FLNA expression and responsiveness of pituitary tumors to pharmacological therapy. No molecular events underlying the reduction of FLNA levels in resistant tumors have been so far identified. FLNA can be phosphorylated by PKA on Ser2152, with increased FLNA resistance to cleavage by calpain and conformational changes affecting FLNA regions involved in SSTR2 and DRD2 binding and signal transduction. In this respect, the effect of cAMP/PKA pathway in the regulation of FLNA stability and/or function by modulating its phosphorylation status could assume particular importance in pituitary, where cAMP cascade plays a crucial role in pituitary cell functions and tumorigenesis. This review will discuss the role of FLNA in the regulation of the main GPCRs target of pharmacological treatment of pituitary tumors, that is, SSTR2 and DRD2, focusing on the effects of cAMP/PKA-mediated FLNA phosphorylation on FLNA biological functions

Expression of protein kinase A regulatory subunits in benign and malignant human thyroid tissues : a systematic review

In this review, we discuss the molecular mechanisms and prognostic implications of the protein kinase A (PKA) signaling pathway in human tumors, with special emphasis on the malignant thyroid. The PKA signaling pathway is differentially activated by the expression of regulatory subunits 1 (R1) and 2 (R2), whose levels change during development, differentiation, and neoplastic transformation. Following the identification of gene mutations within the PKA regulatory subunit R1A (PRKAR1A) that cause Carney complex-associated neoplasms, several investigators have studied PRKAR1A expression in sporadic thyroid tumors. The PKA regulatory subunit R2B (PRKAR2B) is highly expressed in benign, as well as in malignant differentiated and undifferentiated lesions. PRKAR1A is highly expressed in follicular adenomas and malignant lesions with a statistically significant gradient between benign and malignant tumors; however, it is not expressed in hyperplastic nodules. Although the importance of PKA in human malignancy outcomes is not completely understood, PRKAR1A expression correlates with tumor dimension in malignant lesions. Additional studies are needed to determine whether a relationship exists between PKA subunit expression and clinical outcomes, particularly in undifferentiated tumors. In conclusion, the R1A subunit might be a good molecular candidate for the targeted treatment of malignant thyroid tumors

Pituitary Tumors: Genetic and Molecular Factors Underlying Pathogenesis and Clinical Behavior

Pituitary neuroendocrine tumors (PitNETs) are the most common intracranial neoplasms. Although generally benign, they can show a clinically aggressive course, with local invasion, recurrences, and resistance to medical treatment. No universally accepted biomarkers of aggressiveness are available yet, and predicting clinical behavior of PitNETs remains a challenge. In rare cases, the presence of germline mutations in specific genes predisposes to PitNET formation, as part of syndromic diseases or familial isolated pituitary adenomas, and associates to more aggressive, invasive, and drug-resistant tumors. The vast majority of cases is represented by sporadic PitNETs. Somatic mutations in the α subunit of the stimulatory G protein gene (gsp) and in the ubiquitin-specific protease 8 (USP8) gene have been recognized as pathogenetic factors in sporadic GH- and ACTH-secreting PitNETs, respectively, without an association with a worse clinical phenotype. Other molecular factors have been found to significantly affect PitNET drug responsiveness and invasive behavior. These molecules are cytoskeleton and/or scaffold proteins whose alterations prevent proper functioning of the somatostatin and dopamine receptors, targets of medical therapy, or promote the ability of tumor cells to invade surrounding tissues. The aim of the present review is to provide an overview of the genetic and molecular alterations that can contribute to determine PitNET clinical behavior. Understanding subcellular mechanisms underlying pituitary tumorigenesis and PitNET clinical phenotype will hopefully lead to identification of new potential therapeutic targets and new markers predicting the behavior and the response to therapeutic treatments of PitNETs

The amount of cells with Signet Ring Cell morphology has a prognostic impact in poorly cohesive gastric carcinoma

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