This phase II, single-arm, multicenter study examined the efficacy and safety of coltuximab ravtansine (an anti-CD19 antibody drug conjugate) in 61 patients with histologically documented (
or ...transformed) relapsed or refractory diffuse large B-cell lymphoma who had previously received rituximab-containing immuno-chemotherapy. Patients had received a median of 2.0 (range 0-9) prior treatment regimens for diffuse large B-cell lymphoma and almost half (45.9%) had bulky disease (≥1 lesion >5 cm) at trial entry. Patients received coltuximab ravtansine (55 mg/m
) in 4 weekly and 4 biweekly administrations until disease progression or unacceptable toxicity. Forty-one patients were eligible for inclusion in the per protocol population. Overall response rate (International Working Group criteria) in the per protocol population, the primary end point, was 18/41 43.9%; 90% confidence interval (CI:) 30.6-57.9%. Median duration of response, progression-free survival, and overall survival (all treated patients) were 4.7 (range 0.0-8.8) months, 4.4 (90%CI: 3.02-5.78) months, and 9.2 (90%CI: 6.57-12.09) months, respectively. Common non-hematologic adverse events included asthenia/fatigue (30%), nausea (23%), and diarrhea (20%). Grade 3-4 adverse events were reported in 23 patients (38%), the most frequent being hepatotoxicity (3%) and abdominal pain (3%). Eye disorders occurred in 15 patients (25%); all were grade 1-2 and none required a dose modification. Coltuximab ravtansine monotherapy was well tolerated and resulted in moderate clinical responses in pre-treated patients with relapsed/refractory diffuse large B-cell lymphoma. (Registered at:
.
Purpose
The impact of SARS-CoV-2 pandemic on other pathogens is largely unknown. We aimed to compare the prevalence of vaccine-preventable invasive bacterial infections before and during the pandemic ...in Piedmont (Italy).
Methods
We defined the monthly incidence of
S. pneumoniae
,
H. influenzae
and
N. meningitides
-invasive diseases from January 2010 to June 2021. Then, we compared the mean monthly cases during the previous 5 years (2015–2019) and the monthly cases in 2020 or 2021.
Results
We found significant reductions for invasive pneumococcal diseases (IPDs) in adults and
H. influenzae
-invasive diseases in 2020 and 2021 in comparison to the previous years, but not for invasive meningococcal diseases and IPDs in children.
Conclusions
Further data are needed to confirm these findings and define possible post-pandemic evolutions in the epidemiology of vaccine-preventable invasive bacterial diseases.
We have investigated the activity of ITF2357, a novel hydroxamate histone deacetylase inhibitor, on multiple myeloma (MM) and acute myelogenous leukemia (AML) cells in vitro and in vivo. ITF2357 ...induced apoptosis in 8/9 MM and 6/7 AML cell lines, as well as 4/4 MM and 18/20 AML freshly isolated cases, with a mean IC(50) of 0.2 microM. ITF2357 activated the intrinsic apoptotic pathway, upregulated p21 and downmodulated Bcl-2 and Mcl-1. The drug induced hyperacetylation of histone H3, H4 and tubulin. When studied in more physiological conditions, ITF2357 was still strongly cytotoxic for the interleukin-6 (IL-6)-dependent MM cell line CMA-03, or for AML samples maximally stimulated by co-culture on mesenchymal stromal cells (MSCs), but not for the MSCs themselves. Interestingly, ITF2357 inhibited the production of IL-6, vascular endothelial growth factor (VEGF) and interferon-gamma by MSCs by 80-95%. Finally, the drug significantly prolonged survival of severe combined immunodeficient mice inoculated with the AML-PS in vivo passaged cell line already at the 10 mg/kg oral dose. These data demonstrate that ITF2357 has potent anti-neoplastic activity in vitro and in vivo through direct induction of leukemic cell apoptosis. Furthermore, the drug inhibits production of growth and angiogenic factors by bone marrow stromal cells, in particular IL-6 and VEGF.
Direct measurements of the total fusion cross section for B8+40Ar were achieved with the active target technique. The fusion excitation function was extracted at energies near the Coulomb barrier. ...The cross section is well described by a coupled reaction channels calculation. The data were compared with previous B8 fusion experiments on Si28 and Ni58 targets. No evidence of striking enhancement of the total fusion cross section at near the Coulomb barrier, that was previously reported for the B8+58Ni system, was observed in these direct measurements. The present data are systematically consistent with the results for B8+28Si at higher energies and with other weakly-bound systems at near-barrier energies.
Background
Chronic amastigote‐negative cutaneous leishmaniasis (CL) is a diagnostic challenge, as the parasite load may be low, or absent in biopsy tissue sections.
Methods
A series of consecutive ...biopsy specimens, taken from 130 patients with a diagnosis of granulomatous dermatitis of unknown etiology, were reviewed. Polymerase chain reaction (PCR) was carried out for Leishmania‐specific DNA.
Results
A total of 27 of 130 samples were positive for Leishmania‐specific DNA. In only 3 patients was a clinical diagnosis CL made. The lesions were, single or multiple nodules or plaques of many months duration. Histopathologically, a tuberculoid granulomatous dermatitis was the least common denominator in every case, whilst in 5 cases a heavy lymphoid component was predominant. One patient had a concurrent cutaneous marginal zone lymphoma (MZL), the additional PCR study showed the presence of Leishmania DNA in tissue.
Conclusions
The results of this study expand on previous observations as to the deceptive clinicopathologic manifestations of chronic CL, confirming the diagnostic value of PCR analysis for Leishmania DNA in unspecified granulomatous dermatitides. We also suggest that, in countries where Leishmaniasis is endemic, PCR for Leishmania‐specific DNA be performed in any idiopathic pseudolymphomatous. More compelling evidence as to whether chronic Leishmania infection is implicated in the pathogenesis of some cutaneous MZL is warranted by further studies.
State of the art measurements with TexAT Bishop, J; Rogachev, G V; Aboud, E ...
Journal of physics. Conference series,
08/2019, Letnik:
1308, Številka:
1
Journal Article
Recenzirano
Odprti dostop
In the past several years, there has been a large interest of Time Projection Chambers (TPCs) for use in experimental nuclear physics. This has continued in tandem with the requirement for high ...efficiency detectors with low intensity radioactive ion beams. TexAT is a Active Target TPC (AT-TPC) built at Texas A&M University utilizing MICRO MEsh GASeous (MicroMegas) pads and GET electronics developed specifically for TPCs. This design combines good TPC pixelation with a surrounding shell of Si/CsI telescopes to make an extremely versatile detector capable of a wide range of different experimental techniques with only minor modifications to the electronics setup. Two recent experiments performed at the Cyclotron Institute, Texas A&M University, are detailed here demonstrating versatility beyond the usual Thick Target Inverse Kinematics (TTIK) or transfer reactions that these TPCs are more typically used for. The first, a measurement of the 12N → 12C* → 3α decay demonstrates the capabilities of TexAT as a low-energy detector operating at low pressure (20 Torr) to measure β-delayed particle decay. The second, a direct measurement of the 8B+40Ar fusion cross section shows the advantages of operating in active target mode where the target also functions as the detector gas.
Summary
Gemtuzumab ozogamicin (GO) is a humanized anti‐CD33 antibody conjugated with the cytotoxic drug calicheamicin and approved for the treatment of relapsed acute myeloid leukaemia. As ...approximately 18% of acute lymphoblastic leukaemias (ALL) are also CD33 positive, we have investigated the cytotoxic activity of GO on CD33+ ALL cells in vitro and in vivo. 10 ng/ml GO induced 30–95% inhibition of thymidine uptake and 30–70% cell death in four freshly isolated and one in vivo passaged CD33+ ALL‐cell cultures. Furthermore, an in vivo model of a CD33+ ALL carrying the Philadelphia chromosome t(9;22) was established. 5 × 106 ALL‐2 cells inoculated in the tail vein of severe combined immunodeficient mice engrafted into haematopoietic organs, reaching a mean of 70%, 61% and 69% human CD45+ cells in bone marrow, spleen and liver, respectively, at 35 d. To test the therapeutic activity of GO, 50 or 100 μg immunotoxin was inoculated i.p. on days 7, 11 and 15 following tumour‐cell inoculation. GO treatment dramatically inhibited expansion of ALL‐2 cells in all tested organs and increased survival of tumour‐injected animals by 28–41 d, relative to controls. These data demonstrated that GO is active both in vitro and in vivo against CD33+ ALL cells.
A retroviral vector has been constructed that contains the human CD20 cDNA under the control of the Moloney murine leukemia virus (Mo-MuLV) LTR. Freshly isolated mononuclear cells are infected for ...three consecutive days in the presence of PHA and hrlL-2, and a mean 15.9% of the cells (range, 6.5 to 31.7%) acquire a CD3+CD20+ phenotype. Transduced T lymphocytes grow and expand in vitro for up to 3 weeks like mock-infected cells and, as observed for the T lymphoblastoid CEM cell line, CD20 expression is maintained for several months with no change in the growth curve of the cells. CD20-expressing CEM and fresh T lymphocytes can be positively immunoselected on columns using different anti-CD20 antibodies. Exposure to monoclonal chimeric anti-CD20 IgG1(kappa) Rituximab antibody (Roche), in the presence of complement, results in effective and rapid killing of the transduced CD3+CD20+ human T cells in vitro. This approach represents a new and alternative method to gene manipulation with "suicide" genes for the production of drug-responsive T cell populations, a crucial step for the future management of graft-versus-host disease in bone marrow transplant patients.
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