Teatro, attori e subalternità ne Il sogno della camera rossa

The article focuses on a masterpiece of Chinese literature: The Dream of the Red Chamber and investigates into the dynamics governing the relationships between actors and society during the Qing dynasty. This analysis will be carried on by means of significant episodes of the novel. It will be shown how actors are able to establish a micro-society (exemplified by a troupe employed within a court), that is the most actual alternative to the severe and strict dominant schemes. This group is criticized and misunderstood due to its distance from common morality, resulting in a complex mixture of subservience and effective dominance. In fact, its dependent role within elitist society, reveals to be revertible through the development of a symbolic autonomy, opposite to the real decadence of masters, who end up to be the actual servants. The particular freedom carried on by actors, also thanks to their art, becomes the way they use their influence onto the social environment.L’articolo analizza, all’interno dello Honglou Meng, romanzo cardine della letteratura cinese, le dinamiche che regolano il rapporto degli attori con la società di epoca Qing, attraverso alcuni episodi della narrazione. La microsocietà degli attori, esemplificata da una compagnia teatrale alle dipendenze di una corte, rappresenta la più forte alternativa ai rigidi schemi dominant. È un gruppo controverso e frainteso nella sua distanza dalle convenzioni morali, contraddistinto da un complesso connubio di subordinazione e potere effettivo. La sua posizione di sottomissione ad una società elitaria si dimostra infatti rovesciabile, tramite lo sviluppo di un’autonomia simbolica, opposta alla reale condizione decadente dei padroni, che finiscono per esserne asserviti. La particolare libertà di cui l’attore si fa paladino, grazie anche alla propria educazione all’arte, diviene il modo tramite il quale egli esercita un potere sull’ambiente che lo circonda

Studio esplorativo sul ruolo dei microrna circolanti in pazienti affetti da carcinoma colorettale metastatico trattati con regorafenib

Negli ultimi dieci anni la sopravvivenza mediana dei pazienti affetti da carcinoma colorettale metastatico (mCRC) è notevolmente migliorata, passando da circa 12 a più di 24 mesi, grazie all’introduzione di tecniche chirurgiche innovative e di nuove strategie terapeutiche che prevedono la combinazione di farmaci citotossici e farmaci biologici. Nonostante questi progressi la malattia tumorale sviluppa inevitabilmente una resistenza alle terapie sebbene una discreta percentuale di pazienti siano in buone condizioni generali al momento della progressione. Sulla base dei risultati di un ampio studio di fase III è stato recentemente approvato un nuovo farmaco multitarget inibitore di chinasi coinvolte nell’angiogenesi e nella crescita tumorale, regorafenib. Ad oggi regorafenib è indicato nel trattamento di pazienti con mCRC in progressione di malattia dopo aver ricevuto tutte le altre terapie disponibili. In una consistente percentuale di pazienti la malattia progredisce rapidamente entro le prime settimane di trattamento con regorafenib ed inoltre l’impiego di questo farmaco può determinare l’insorgenza di specifici effetti collaterali, talora gravi, oltre ad aumentare drasticamente i costi delle terapie. Per questi motivi la razionalizzare dell’impiego di tale farmaco, tramite l’identificazione di caratteristiche cliniche e/o biomolecolari che possano predire la risposta o la resistenza al trattamento è una necessità impellente. Negli ultimi anni è stato ipotizzato che microRNA (miRNA) circolanti, piccole molecole lunghe appena 20 nucleotidi, possano condizionare la cancerogenesi dei tumori colorettali tramite la regolazione di oncosoppressori e oncogeni e possano avere un ruolo diagnostico, prognostico e/o predittivo. Per questo ragioni abbiamo condotto uno studio esplorativo allo scopo di valutare l’andamento dei livelli plasmatici di 10 miRNA circolanti, scelti sulla base del loro già noto ruolo prognostico, in 34 pazienti con mCRC trattati con regorafenib presso il Polo Oncologico dell’Azienda Ospedaliero-Universitaria Pisana. Le caratteristiche principali dei 34 pazienti trattati erano: rapporto maschi / femmine, 50% / 50%; età mediana, 65 anni (range 46-78), ECOG Performance Status 0 / 1-2, 71% / 29%; tempo intercorso tra diagnosi di malattia metastatica e trattamento con regorafenib < / ≥ 18 mesi, 65% / 35%. È stato osservato un tasso di risposta del 3% e una stabilizzazione di malattia nel 47% dei casi. Ad un follow-up mediano di 9.1 mesi, la sopravvivenza libera da progressione (PFS) e la sopravvivenza globale (OS) mediane sono risultate, rispettivamente, di 2.4 e 6.5 mesi. Complessivamente è stata osservato un incremento significativo dei livelli plasmatici mediani tra il primo e il quindicesimo giorno di terapia nei miR-601 (p=0.01), miR-141 (p=0.04) e miR-21 (p=0.06). Nonostante l’incremento mediano osservato nella popolazione generale dei livelli circolanti di miR-21 al quindicesimo giorno, in 12 pazienti (35%) si è riscontrata una riduzione vs 22 pazienti (65%) in cui si è registrato un aumento. Correlando la variazione dei livelli di miR-21 con la risposta al trattamento si è verificato che: miR-21 si è ridotto in 3 dei 17 (18%) pazienti rapidamente progrediti al trattamento e in 9 dei 17 (53%) pazienti che hanno ottenuto una risposta o una stabilizzazione della malattia (Fisher's Exact Test, p=0.035). Valutando i parametri standard di accuratezza di un test diagnostico, la misurazione dei livelli di miR-21 ha mostrato una sensibilità dell’82% e una valore predittivo negativo dell’75% nel predire il beneficio dal trattamento con regorafenib. La PFS e la OS mediane dei pazienti in cui è stata osservata una riduzione del miR-21 sono risultate rispettivamente di 3.9 e 7.8 mesi, mentre nei pazienti in cui il miR-21 è incrementato sono risultate di 2.1 e 5.8 mesi rispettivamente. Questi dati trovano un forte razionale biologico, infatti miR-21 è un miRNA oncogenico che modula l’espressione di numerosi geni implicati nella progressione tumorale, tra i quali PTEN e timidilato sintetasi. E’ iperespresso in numerose neoplasie e in particolare nel CRC elevati livelli di espressione sono stati associati a progressione di malattia e peggiore prognosi. Questa analisi esplorativa identifica nella variazione precoce dei livelli plasmatici di miR-21 un potenziale marker predittivo di risposta al trattamento con regorafenib. I risultati ottenuti saranno verificati in uno studio prospettico ad oggi in corso

a retrospective study of trifluridine tipiracil in pretreated metastatic colorectal cancer patients in clinical practice

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Clinical impact of first-line bevacizumab plus chemotherapy in metastatic colorectal cancer of mucinous histology: a multicenter, retrospective analysis on 685 patients

In metastatic colorectal cancer (MCRC), mucinous histology has been associated with poor response rate and prognosis. We investigated whether bevacizumab combined with different chemotherapy regimens may have an impact on clinical outcomes of MCRC patients with mucinous histology

Location of primary tumor and benefit from anti-epidermal growth factorreceptor monoclonalantibodies in patients with RAS and BRAF wild-typemetastatic colorectal cancer

Introduction. Right- and left-sided colorectal cancers (CRCs) differ in clinical and molecular characteristics. Some retrospective analyses suggested that patients with right-sided tumors derive less benefit from anti-epidermal growth factor receptor (EGFR) antibodies; however, molecular selection in those studies was not extensive. Patients and Methods. Patients with RAS and BRAF wild-type metastatic CRC (mCRC) who were treated with single-agent anti-EGFRs or with cetuximab-irinotecan (if refractory to previous irinotecan) were included in the study. Differences in outcome between patients with right- and left-sided tumors were investigated. Results. Of 75 patients, 14 and 61 had right- and left-sided tumors, respectively. None of the right-sided tumors responded according to RECIST, compared with 24 left-sided tumors (overall response rate: 0% vs. 41%; p 5 .0032), and only 2 patients with right-sided tumors (15%) versus 47 patients with left-sided tumors (80%) achieved disease control (p, .0001). The median duration of progression-free survival was 2.3 and 6.6 months in patients with right-sided and left-sided tumors, respectively (hazard ratio: 3.97;95%confidence interval: 2.09–7.53; p,.0001). Conclusion. Patients with right-sided RAS and BRAF wild-type mCRC seemed to derive no benefit from single-agent anti- EGFRs

Upfront Modified Fluorouracil, Leucovorin, Oxaliplatin, and Irinotecan Plus Panitumumab Versus Fluorouracil, Leucovorin, and Oxaliplatin Plus Panitumumab for Patients With RAS/BRAF Wild-Type Metastatic Colorectal Cancer: The Phase III TRIPLETE Study by GONO

PURPOSE To verify whether the intensification of the upfront chemotherapy backbone with a modified schedule of modified fluorouracil, leucovorin, oxaliplatin, and irinotecan (mFOLFOXIRI) increases the activity of fluorouracil, leucovorin, and oxaliplatin when both regimens are combined with panitumumab as initial treatment for RAS and BRAF wild-type (wt) metastatic colorectal cancer (mCRC).METHODS TRIPLETE was a prospective, open-label, phase III trial in which previously untreated patients with unresectable RAS and BRAF wt mCRC were randomly assigned 1:1 to modified FOLFOX/panitumumab (control group) or mFOLFOXIRI/panitumumab (experimental group) up to 12 cycles, followed by fluorouracil/-leucovorin/panitumumab until disease progression. The primary end point was objective response rate (ORR) according to RECIST 1.1. Hypothesizing an ORR of 60% in the control group, 432 cases provided 90% power to a two-sided chi-square test for heterogeneity with a two-sided alpha error of .05 to detect &gt;= 15% differences between arms (ClinicalTrials.gov identifier: NCT03231722).RESULTS From September 2017 to September 2021, 435 patients were enrolled (control group/experimental group: 217/218) in 57 Italian sites. One hundred sixty (73%) patients treated with mFOLFOXIRI plus panitumumab and 165 (76%) patients treated with modified FOLFOX plus panitumumab achieved RECIST response (odds ratio 0.87, 95% CI, 0.56 to 1.34, P= .526). No differences in early tumor shrinkage rate (57%/58%, P = .878) and deepness of response (median: 48%/47%, P = .845) were reported, nor in RO resection rate (25%/29%, P = .317). No significant difference between arms was reported in terms of progression-free survival (median progression-free survival: 12.7 in the experimental group v 12.3 months in the control group, hazard ratio: 0.88, 95% CI, 0.70 to 1.11, P = .277).CONCLUSION The intensification of the upfront chemotherapy backbone in combination with panitumumab does not provide additional benefit in terms of treatment activity at the price of increased gastrointestinal toxicity in patients with RAS and BRAF wt mCRC. (C) 2022 by American Society of Clinical Oncolog

The Inflammatory Feed-Forward Loop Triggered by the Complement Component C3 as a Potential Target in Endometriosis

Copyright © 2021 Agostinis, Zorzet, Balduit, Zito, Mangogna, Macor, Romano, Toffoli, Belmonte, Morello, Martorana, Borelli, Ricci, Kishore and Bulla. The complement system is a major component of humoral innate immunity, acting as a first line of defense against microbes via opsonization and lysis of pathogens. However, novel roles of the complement system in inflammatory and immunological processes, including in cancer, are emerging. Endometriosis (EM), a benign disease characterized by ectopic endometrial implants, shows certain unique features of cancer, such as the capacity to invade surrounding tissues, and in severe cases, metastatic properties. A defective immune surveillance against autologous tissue deposited in the peritoneal cavity allows immune escape for endometriotic lesions. There is evidence that the glandular epithelial cells found in endometriotic implants produce and secrete the complement component C3. Here, we show, using immunofluorescence and RT-qPCR, the presence of locally synthesized C3 in the ectopic endometriotic tissue, but not in the eutopic tissue. We generated a murine model of EM via injection of minced uterine tissue from a donor mouse into the peritoneum of recipient mice. The wild type mice showed greater amount of cyst formation in the peritoneum compared to C3 knock-out mice. Peritoneal washings from the wild type mice with EM showed more degranulated mast cells compared to C3 knock-out mice, consistent with higher C3a levels in the peritoneal fluid of EM patients. We provide evidence that C3a participates in an auto-amplifying loop leading to mast cell infiltration and activation, which is pathogenic in EM. Thus, C3 can be considered a marker of EM and its local synthesis can promote the engraftment of the endometriotic cysts.Ministry of Health: Project code: ENDO-2020-23670288 “Pathogenesis of endometriosis: the role of genes, inflammation and environment”; Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy (RC20/16, RC23/18; 5MILLE15D; PORFESR 2014/2020 FVG (“TiCheP” project)

TRIPLETE: A randomised phase III study of modified FOLFOXIRI plus panitumumab versus mFOLFOX6 plus panitumumab as initial therapy for patients with unresectable RAS and BRAF wild-type metastatic colorectal cancer

FOLFOXIRI plus bevacizumab is considered a standard option in the upfront treatment of clinically selected patients with metastatic colorectal cancer irrespective of RAS and BRAF molecular status. The randomised MACBETH and VOLFI studies showed that a modified FOLFOXIRI regimen in combination with cetuximab or panitumumab, respectively, achieved high therapeutic activity in RAS and BRAF wild-type patients with an acceptable toxicity profile. Drawing from these considerations, we designed TRIPLETE study aiming at comparing two different chemotherapy backbones (mFOLFOXIRI or mFOLFOX6) in combination with panitumumab in the first-line treatment of patients with RAS and BRAF wild-type metastatic colorectal cancer. Methods This is a prospective, open-label, multicentre phase III trial in which initially unresectable and previously untreated RAS and BRAF wild-type metastatic colorectal cancer patients are randomised to receive a standard treatment with mFOLFOX6 plus panitumumab or an experimental regimen with modified FOLFOXIRI (irinotecan 150 mg/m 2, oxaliplatin 85 mg/m 2, L-leucovorin 200 mg/m 2, 5-fluoruracil 2400 mg/m 2 48-hour continuous infusion) plus panitumumab up to 12 cycles, followed by panitumumab plus 5-fluorouracil and L-leucovorin until disease progression. The primary endpoint is overall response rate according to RECIST 1.1 criteria. Discussion The relative benefit of chemotherapy intensification when using an anti-EGFR-based regimen in molecularly selected patients is unknown; TRIPLETE study aims at filling this gap of knowledge. The study is sponsored by the Gruppo Oncologico Nord Ovest Cooperative Group and is currently ongoing at 42 Italian centres. Clinical trial information NCT03231722

Colorectal neoplastic emergencies in immunocompromised patients: preliminary result from the Web-based International Register of Emergency Surgery and Trauma (WIRES-T trial)

Association of advanced age, neoplastic disease and immunocompromission (IC) may lead to surgical emergencies. Few data exist about this topic. Present study reports the preliminary data from the WIRES-T trial about patients managed for colorectal neoplastic emergencies in immunocompromised patients. The required data were taken from a prospective observational international register. The study was approved by the Ethical Committee with approval n. 17575; ClinicalTrials.gov Identifier: NCT03643718. 839 patients were collected; 753 (80.7%) with mild-moderate IC and 86 (10.3%) with severe. Median age was 71.9 years and 73 years, respectively, in the two groups. The causes of mild-moderate IC were reported such malignancy (753-100%), diabetes (103-13.7%), malnutrition (26-3.5%) and uremia (1-0.1%), while severe IC causes were steroids treatment (14-16.3%); neutropenia (7-8.1%), malignancy on chemotherapy (71-82.6%). Preoperative risk classification were reported as follow: mild-moderate: ASA 1-14 (1.9%); ASA 2-202 (26.8%); ASA 3-341 (45.3%); ASA 4-84 (11.2%); ASA 5-7 (0.9%); severe group: ASA 1-1 patient (1.2%); ASA 2-16 patients (18.6%); ASA 3-41 patients (47.7%); ASA 4-19 patients (22.1%); ASA 5-3 patients (3.5%); lastly, ASA score was unavailable for 105 cases (13.9%) in mild-moderate group and in 6 cases (6.9%) in severe group. All the patients enrolled underwent urgent/emergency surgery Damage control approach with open abdomen was adopted in 18 patients. Mortality was 5.1% and 12.8%, respectively, in mild-moderate and severe groups. Long-term survival data: in mild-moderate disease-free survival (median, IQR) is 28 (10-91) and in severe IC, it is 21 (10-94). Overall survival (median, IQR) is 44 (18-99) and 26 (20-90) in mild-moderate and severe, respectively; the same is for post-progression survival (median, IQR) 29 (16-81) and 28, respectively. Univariate and multivariate analyses showed as the only factor influencing mortality in mild-moderate and severe IC is the ASA score. Colorectal neoplastic emergencies in immunocompromised patients are more frequent in elderly. Sigmoid and right colon are the most involved. Emergency surgery is at higher risk of complication and mortality; however, management in dedicated emergency surgery units is necessary to reduce disease burden and to optimize results by combining oncological and acute care principles. This approach may improve outcomes to obtain clinical advantages for patients like those observed in elective scenario. Lastly, damage control approach seems feasible and safe in selected patients