Reduced-intensity allogeneic hematopoietic stem cell transplantation in metastatic colorectal cancer as a novel adoptive cell therapy approach. The European group for blood and marrow transplantation experience

Abstract Reduced-intensity conditioning (RIC) regimens for allogeneic hematopoietic stem cell transplantation (HCT) allowed the existence of an allogeneic cell-mediated antitumor effect in metastatic colorectal cancer (mCRC) to be explored. We report on 39 patients with progressing mCRC treated with different RIC regimens in a multicenter clinical trial of the European Bone Marrow Transplantation Group. Disease status at transplant was progressive disease (PD) in 31 patients (80%), stable disease (SD) in 6 (15%), and partial response (PR) in 2 (5%). All patients engrafted (median donor T cell chimerism of 90% at day +60). Transplant-related morbidities were limited. Grades II-IV acute graft-versus-host disease (aGVHD) occurred in 14 patients (35%) and chronic GVHD (cGVHD) in 9 patients (23%). Transplant-related mortality occurred in 4 patients (10%). The best tumor responses were: 1 complete response (CR) (2%), 7 PR (18 %), and 10 SD (26%), giving an overall disease control in 18 of 39 patients (46%). Allogeneic HCT after RIC is feasible; the collected results compared favorably in terms of tumor response with those observed using conventional approaches beyond second-line therapies. The study of an allogeneic cell based therapy in less advanced patients is warranted

I tumori cistici del pancreas. Revisione della letteratura e proposta di un percorso diagnostico-terapeutico

In questo lavoro, gli Autori esaminano gli aspetti epidemiologici, clinici, anatomo-patologici, morfologico-strumentali e chimico-fisici propri di ogni singolo tipo di lesione cistica del pancreas e li paragonano tra di loro in maniera critica. In tal modo riescono ad individuare per ogni singola categoria le caratteristiche più salienti. Un percorso composto di quattro gruppi principali di esami strumentali e di laboratorio (ecografia addominale standard / EUS, TC, RM, FNA / biopsia / dosaggio di oncomarkers ed amilasi del contenuto cistico) è stato prescelto per l’acquisizione di tutti questi dati in virtù di precisi criteri di specificità, sensibilità ed accuratezza diagnostica forniti dalla letteratura scientifica internazionale. Per ogni sottogruppo di tumore cistico del pancreas viene proposto, infine, il piano terapeutico accreditato di miglior successo, sempre secondo la comune opinione scientifica internazional

Colon cancer adrenal metastasis: case report and review of the literature

The authors report a case of alone right adrenal metastasis from colon carcinoma discovered incidentally by CT scan imaging 4 years after colon resection in a 74-year-old man. The presence of metastasis in the adrenal glands represents the second most frequent cause of “adrenal incidentaloma”, following cortical-adrenal adenomas. The most common primary tumors responsible for adrenal metastasis are carcinoma of the lung, breast and kidney. Alone adrenal metastases due to colon or rectal carcinoma is very rare. Due to their rarity, at present there are not randomised studies supporting the effectiveness of surgery. Nevertheless, on the basis of international Literature and our experience of adrenalectomy could represent the current “gold-standard” therapeutic approach

New paradigm for nano–bio interactions: multimolecular assembly of a prototypical disordered protein with ultrasmall nanoparticles

Understanding the interactions between nanoparticles (NPs) and proteins is crucial for the successful application of NPs in biological contexts. Protein adsorption is dependent on particle size, and protein binding to ultrasmall (1–3 nm) NPs is considered to be generally weak. However, most studies have involved structured biomacromolecules, while the interactions of ultrasmall NPs with intrinsically disordered proteins (IDPs) have remained elusive. IDPs are abundant in eukaryotes and found to associate with NPs intracellularly. As a model system, we focused on ultrasmall gold nanoparticles (usGNPs) and tau, a cytosolic IDP associated with Alzheimer’s disease. Using site-resolved NMR, steady-state fluorescence, calorimetry, and circular dichroism, we reveal that tau and usGNPs form stable multimolecular assemblies, representing a new type of nano–bio interaction. Specifically, the observed interaction hot spots explain the influence of usGNPs on tau conformational transitions, with implications for the intracellular targeting of aberrant IDP aggregation

Allogeneic nonmyeloablative hematopoietic cell transplantation in metastatic colon cancer: tumor-specific T-cells directed to a tumor-associated antigen are generated in vivo during GVHD. Blood

A pilot study was conducted to evaluate safety and activity of nonmyeloablative allogeneic hematopoietic cell transplantation (HCT) in colorectal carcinoma (CRC) and to determine whether a T-cell response to a tumor-associated antigen (TAA) was induced. Fifteen patients with metastatic CRC underwent HCT from human leukocyte antigen (HLA)-matched siblings after a nonmyeloablative conditioning regimen. All patients engrafted with a median donor T-cell chimerism of 72% at day ؉56. Eight patients experienced grades II to IV acute graft-versushost disease (GVHD). Despite progressive disease before HCT, partial remission and disease stabilization longer than 90 days were observed in 1 and 3 patients, respectively. Induction of TAA-specific T cells was evaluated with a carcinoembryonic antigen (CEA)-specific HLA-A*0201 pentamer in 6 patients with CRC. CEA-specific CD8 ؉ T cells were detected in 3 of 3 patients concomitant with GHVD onset, but not in 3 of 3 patients without GVHD. They were also not detected in 9 of 9 control patients with GVHD who received transplants for diagnoses other than CRC. Antitumor activity of CEAspecific T cells was also validated in vitro. In one patient, the induction of CEA-specific T cells was associated with a decrease of serum CEA levels and a partial response