An alternative synthetic approach for 1,3- benzoxazine derivatives

1,3-benzoxazine derivatives were synthesized in high yield using three-step synthetic technique by the condensation of 2-hydroxybenzaldehyde with aromatic amines, reducing the condensation products and replacing the usual formaldehyde with methylene bromide to achieve ring closure. The structures of the benzoxazines were confirmed by FTIR, 1H and 13C NMR spectra and Mass spectroscopy

Primary mediastinal large B-cell lymphoma (PMLBCL): long-term results from a retrospective multicentre Italian experience in 138 patients treated with CHOP or MACOP-B/VACOP-B

The optimal treatment of primary mediastinal large B-cell lymphoma (PMLBCL) is still undefined. In the absence of randomised studies, we retrospectively analysed: (a) the effectiveness of two chemotherapy regimens (CHOP vs MACOP-B/VACOP-B) in complete remission (CR) achievement and event-free survival (EFS) and (b) the role of mediastinal involved-field radiotherapy (IF-RT) as consolidation. From 1982 to 1999, 138 consecutive patients affected by PMLBCL were treated in 13 Italian institutions with CHOP (43) or MACOP-B/VACOP-B (95). The two groups of patients were similar as regard to age, gender, presence of bulky mediastinal mass, pleural effusion, stage and international prognostic indexes category of risk. Overall, 75.5% of patients in CR received IF-RT as consolidation. Complete remission was 51.1% in the CHOP group and 80% in MACOP-B/VACOP-B (P<0.001). Relapse occurred in 22.7% of CHOP- and in 9.2% of MACOP-B/VACOP-B-treated patients (n.s.). Event-free patients were 39.5% in CHOP and 75.7% in the MACOP-B/VACOP-B group (P<0.001). The addition of IF-RT as consolidation improved the outcome, irrespectively of the type of chemotherapy (P=0.04). At a multivariate analysis, achievement of CR (P<0.0001) and type of CT (MACOP-B/VACOP-B) retained the significance for OS (P=0.008) and EFS (P=0.03). In our experience, MACOP-B/VACOP-B appears to positively influence OS and EFS in patients affected by PMLBCL, as compared to CHOP. Consolidation IF-RT on mediastinum further improves the outcome of CR patients

A role of BRCA1 and BRCA2 germline mutations in breast cancer susceptibility within Sardinian population

<p>Abstract</p> <p>Background</p> <p>In recent years, numerous studies have assessed the prevalence of germline mutations in <it>BRCA1 </it>and <it>BRCA2 </it>genes in various cohorts. We here extensively investigated the prevalence and geographical distribution of <it>BRCA1-2 </it>mutations in the entire genetically-homogeneous Sardinian population. The occurrence of phenotypic characteristics which may be predictive for the presence of <it>BRCA1-2 </it>germline mutations was also evaluated.</p> <p>Methods</p> <p>Three hundred and forty-eight breast cancer patients presenting a familial recurrence of invasive breast or ovarian carcinoma with at least two affected family members were screened for <it>BRCA1-2 </it>mutations by DHPLC analysis and DNA sequencing. Association of <it>BRCA1 </it>and <it>BRCA2 </it>mutational status with clinical and pathological parameters was evaluated by Pearson's Chi-Squared test.</p> <p>Results and Conclusion</p> <p>Overall, 8 <it>BRCA1 </it>and 5 <it>BRCA2 </it>deleterious mutations were detected in 35/348 (10%) families; majority (23/35;66%) of mutations was found in <it>BRCA2 </it>gene. The geographical distribution of <it>BRCA1-2 </it>mutations was related to three specific large areas of Sardinia, reflecting its ancient history: <it>a</it>) the Northern area, linguistically different from the rest of the island (where a <it>BRCA2 c.8764_8765delAG </it>mutation with founder effect was predominant); <it>b</it>) the Middle area, land of the ancient Sardinian population (where <it>BRCA2 </it>mutations are still more common than <it>BRCA1 </it>mutations); and <it>c</it>) the South-Western area, with many Phoenician and Carthaginian locations (where <it>BRCA1 </it>mutations are prevalent). We also found that phenotypic features such as high tumor grading and lack of expression of estrogen/progesterone receptors together with age at diagnosis and presence of ovarian cancer in the family may be predictive for the presence of <it>BRCA1-2 </it>germline mutations.</p

Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Lymphoma risk is elevated for relatives with common non-Hodgkin lymphoma (NHL) subtypes, suggesting shared genetic susceptibility across subtypes. To evaluate the extent of mutual heritability among NHL subtypes and discover novel loci shared among subtypes, we analyzed data from eight genome-wide association studies within the InterLymph Consortium, including 10,629 cases and 9505 controls. We utilized Association analysis based on SubSETs (ASSET) to discover loci for subsets of NHL subtypes and evaluated shared heritability across the genome using Genome-wide Complex Trait Analysis (GCTA) and polygenic risk scores. We discovered 17 genome-wide significant loci (P &lt; 5 × 10−8) for subsets of NHL subtypes, including a novel locus at 10q23.33 (HHEX) (P = 3.27 × 10−9). Most subset associations were driven primarily by only one subtype. Genome-wide genetic correlations between pairs of subtypes varied broadly from 0.20 to 0.86, suggesting substantial heterogeneity in the extent of shared heritability among subtypes. Polygenic risk score analyses of established loci for different lymphoid malignancies identified strong associations with some NHL subtypes (P &lt; 5 × 10−8), but weak or null associations with others. Although our analyses suggest partially shared heritability and biological pathways, they reveal substantial heterogeneity among NHL subtypes with each having its own distinct germline genetic architecture

Correction: Distinct germline genetic susceptibility profiles identified for common non-Hodgkin lymphoma subtypes

Correction to: Leukemia https://doi.org/10.1038/s41375-022-01711-0, published online 22 October 202

Newly diagnosed cases of hematologic malignancies in Sardinia in the early 2000s: an estimation of their number, age and geographic distribution on the basis of a previous epidemiologic survey

We estimate the number of cases of hematologic malignancies expected to be newly diagnosed in the resident population of Sardinia during the year 2001, and classify the predicted cases according to disease, age and geographic distribution, The implications of these predictions for the Sardinian health care system are discussed, particularly with respect to the development of policies aimed to ensure the most adequate medical care

BRCA1 and BRCA2 germline mutations in Sardinian breast cancer families

20118 Background: Germline alterations in the BRCA1 and BRCA2 genes highly predispose to breast and ovarian cancer. In families with BRCA1/2 mutations, identification of mutation carriers is clinically rilevant in view of the options for surveillance and prevention. The general aim of the present research is to contribute to the molecular epidemiology of BRCA1/2 genes in the italian region of Sardinia as a prerequisite for a prevention program based on DNA analysis. Methods: Fifty-two of 172 patients diagnosed with primary invasive breast carcinomas (n = 150) or ovarian cancer (n = 18) and 4 male with breast cancer referring to our departments between 2003 and 2005, had a positive family history for breast and/or ovarian cancer and were selected for BRCA1/2 mutation screening by denaturing high-performance liquid chromatography and DNA sequencing. Onehundred DNAs from healthy women originating from the same geographical area were used as population controls. Results: We identified 7 BRCA sequence alterations: 3 were already described polymorphisms while 4 novel BRCA variants were found in 11 out of 52 (21%) probands. The BRCA23951del3insAT is a novel deleterious mutation which leads to protein truncation at codon 1258 and co-occurred with the missense BRCA2S2546P in 6 probands originating from the same village and in none of the controls. Segregation analysis suggested the cis-position of the two mutations. All mutation carriers shared a common disease-associated BRCA2 haplotype indicating the presence of a founder effect. The BRCA2N272I was first observed in our population and was found in 3 unrelated probands and in none of 200 control chromosomes. The missense BRCA1E1352K mutation was present in 3 patients from two unrelated families with breast and ovarian cancer cases in three generations. Conclusions: In the present study, BRCA2 are more recurrent than BRCA1 mutations as reported for the northern part of the island. Our findings provide new epidemiological data that may be useful in defining the prevalence, mutational spectrum and penetrance of BRCA1/2 in the genetically homogeneous population of Sardinia. A comprehensive map of the BRCA mutations may facilitate screening/testing for inherited risk of breast cancer. No significant financial relationships to disclose. </jats:p