The Desired Effect : Pontiac\u27s Rebellion and the Native American Struggle to Survive in Britain\u27s North American Conquest

Ravaged by war and in debt after its victory in the French and Indian War, Britain was not only recuperating, but rejoicing over the signing of the Treaty of Paris in 1763. This treaty officially ended the fighting and gave Britain all of the land east of the Mississippi River, formerly owned by the French. The ink on the treaty was barely dry when a new insurgence arose in British occupied North America. Native Americans, dissatisfied after the war with their position as conquered people and not as allies, rebelled collectively against British colonists and forts along the frontier. Before the war had started, the French had traded and lived among the Native Americans, but perhaps most importantly, they had given them presents to show respect and diplomacy. The Native Americans had grown accustomed to this act of friendliness and when Britain, in debt after the war, wanted to considerably reduce the number of gifts given, there were severe consequences. In 1763, the Native Americans led an insurgence, commonly called Pontiac’s Rebellion because of Pontiac, the Ottawa leader. This insurgence would culminate in the first extensive multi-tribal resistance to European colonization in America. In response to Britain’s new policies, the Native Americans took ten of their forts, which led not only to excess in conflict, but to the British exposing smallpox blankets onto the Native Americans

Impressive long-term response with pertuzumab and trastuzumab in HER2-positive breast cancer with brain metastasis

This is a case report of a 40-year-old woman who, after conservative breast cancer treatment, developed a HER2 positive solitary brain metastasis in the left temporal lobe, without extracranial disease. She underwent surgery resection followed by stereotactic radiotherapy and, because of early brain progression, she was submitted to the first line therapy with pertuzumab, trastuzumab and weekly paclitaxel. After six months of treatment, a brain magnetic resonance imaging revealed a complete disappearance of brain recurrence, which persisted for more than 24 months

Ampelographic and Molecular Characterisation of Aglianico Accessions (Vitis vinifera L.) Collected in Southern Italy

To characterise 31 different Aglianico accessions randomly collected in Southern Italy, 30 ampelographicdescriptors, 13 SSRs and 10 AFLP primer combinations were analysed. An appreciable variation ofampelographic descriptors was revealed mainly by mature leaf traits, while very few variations wererecorded for shoot and berry traits. Similarly, all SSR loci revealed molecular monomorphism and AFLPswith a very high genetic similarity (Dice coefficient) among all the accessions considered. One of the aimsof this study was to clarify the genetic assessment of Aglianico Nero and Aglianico del Vulture Nero,since they are registered as two different cultivars with distinct varietal codes at the Italian Register ofGrape Varieties. Registered Aglianico Nero and Aglianico del Vulture Nero were included in the analyses,compared and used as reference material. Our plants showed that all the accessions tested, independentfrom the biotype, and the two registered cultivars belong to the same genotype, suggesting that, as reportedby the Vitis International Variety Catalogue, a case of synonymy occurred between Aglianico Nero andAglianico del Vulture Nero. These cultivars could therefore be considered as a single cultivar. Moreover,the AFLP data revealed a partial match between morphological and molecular data, showing that theAFLP molecular method was able to discriminate between different accessions belonging to the samecultivar

Evidence of non-seed transmission of viruses in grapevine breeding material

The vertical transmission of viruses is an important phenomenon affecting a wide range of viruses and host plants. Nevertheless, the presence of virus in a seed does not always lead to seedling infection. In grapevine, seed transmission has been reported for many nepoviruses, but little is known about Leafroll, Rugose wood complex and Fleck diseases. Thus, the aim of this study is to monitor the virological condition of seedlings obtained by crosses between infected parents, analyzing the sanitary status of seedlings after the transfer in experimental fields. It was observed that, although the viral state of parents was quite compromised, viruses were not detected in any of the 150 progeny plants, demonstrating that the main grapevine viruses are at low risk for seed transmission

Bevacizumab in association with de Gramont 5-fluorouracil/folinic acid in patients with oxaliplatin-, irinotecan-, and cetuximab-refractory colorectal cancer: a single-center phase 2 trial.

BACKGROUND: The aim of the current study was the investigation of the value of bevacizumab+5-fluorouracil(5-FU)/folinic acid in patients with advanced colorectal cancers who have exhausted standard chemotherapy options. METHODS: The authors included 48 heavily pretreated patients (colon:rectum, 33:15; men:women, 23:25; median age, 63 years; range, 27-79 years) whose disease had progressed during or within an oxaliplatin-based first-line chemotherapy, an irinotecan-based second-line regimen, and a third-line treatment with cetuximab plus weekly irinotecan. Bevacizumab was given at a dose of 5 mg/kg. 5-FU/folinic acid was administered according to the de Gramont schedule. RESULTS: The response rate was 6.25%, and 30.4% of patients demonstrated stable disease as the best response. The median time to disease progression was 3.5 months (95% confidence interval [95% CI], 2.3-6.9 months), and the median survival time was 7.7 months (95% CI, 3.9-11.9 months). The most common grade 3 to 4 side toxicities (graded according to the National Cancer Institute Common Toxicity Criteria [version 2.0]) were: diarrhea (20.8%), fatigue (14.5%), and stomatitis (12.5%). Grade 3 to 4 hemorrhage occurred in 8 patients (16.6%), including 4 cases of bleeding in the gastrointestinal tract. Other relatively common adverse events such as hypertension, thrombosis, and bowel perforation were reported in 50%, 18.7%, and 4.16%, of patients respectively. CONCLUSIONS: The data from the current study suggest a modest but significant clinical benefit of bevacizumab+de Gramont schedule in heavily pretreated colorectal cancer patients. Copyright (c) 2009 American Cancer Society

progression free survival pfs benefit from first line endocrine based therapies in postmenopausal women with hr her2 metastatic breast cancer mbc according to different prognostic subgroups a combined analysis of data from paloma 2 monaleesa 2 monarch 3 falcon swog and fact trials

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Optimizing PD-L1 evaluation on cytological samples from advanced non-small-cell lung cancer

Aim: Programmed cell death-ligand 1 (PD-L1) predicts response to immune checkpoint inhibitors in non-small-cell lung cancer (NSCLC) patients. Most NSCLCs are diagnosed at an advanced stage and using minimally invasive diagnostic procedures that yield small biopsies or cytological samples. Methods: Cytological smears and paired histological samples from 52 advanced NSCLC patients were tested for PD-L1 expression by immunocyto/histochemistry (ICC/IHC) and for PD-L1 gene status by FISH. Results: PD-L1 was overexpressed in 9/52 (17%) cytological samples and in seven (13.5%) matched biopsies. The concordance between immunocytochemistry and IHC was 92.3% (48/52; p < 0.001). The concordance between PD-L1 gene status on cytology and histology was 69.2% (18/26; p < 0.001). No correlation between IHC and fluorescence in situ hybridization results was found. Conclusion: Our data support the feasibility and reliability of PD-L1 protein and PD-L1 gene assessment on direct cytological smears from NSCLC patients whenever histological sample are inadequate

Should all patients with HR-positive HER2-negative metastatic breast cancer receive CDK 4/6 inhibitor as first-line based therapy? A network meta-analysis of data from the PALOMA 2, MONALEESA 2, MONALEESA 7, MONARCH 3, FALCON, SWOG and FACT trials

Background: We aim to understand whether all patients with hormonal receptor (HR)-positive (+)/human epidermal growth factor receptor-2 (HER2)-negative (−) metastatic breast cancer (MBC) should receive cyclin D-dependent kinase (CDK) 4/6 inhibitor-based therapy as a first-line approach. Methods: A network meta-analysis (NMA) using the Bayesian hierarchical arm-based model, which provides the estimates for various effect sizes, were computed. Results: First-line treatment options in HR+/HER2− MBC, including CDK 4/6 inhibitors combined with aromatase inhibitors (AIs) or fulvestrant (F), showed a significantly longer progression-free survival (PFS) in comparison with AI monotherapy, with a total of 26% progression risk reduction. In the indirect comparison across the three classes of CDK 4/6 inhibitors and F endocrine-based therapies, the first strategy resulted in longer PFS, regardless of specific CDK 4/6 inhibitor (HR: 0.68; 95% CrI: 0.53–0.87 for palbociclib + AI, HR: 0.65; 95% CrI: 0.53–0.79 for ribociclib + AI, HR: 0.63; 95% CrI: 0.47–0.86 for abemaciclib + AI) and patient’s characteristics. Longer PFS was also found in patients with bone-only and soft tissues limited disease treated with CDK 4/6 inhibitors. Conclusions: CDK 4/6 inhibitors have similar efficacy when associated with an AI in the first-line treatment of HR+ MBC, and are superior to either F or AI monotherapy, regardless of any other patients or tumor characteristics

Comparison of HER2 status in primary and paired metastatic sites of gastric carcinoma

Background: Trastuzumab has recently shown efficacy in the treatment of HER2-positive advanced gastric adenocarcinoma. Although antibody-based therapies target the metastatic disease, HER2 status is usually evaluated in the primary tumour because metastatic sites are rarely biopsied. The aim of this study was to compare HER2 status in primary and paired metastatic sites of gastric adenocarcinoma. Methods: The HER2 status was assessed by fluorescence in situ hybridisation (FISH) and immunohistochemistry (IHC) in 72 secondary lesions of gastric adenocarcinoma and in the corresponding primary tumours. Results: Concordance of FISH results, evaluable in 68 primary and matched metastatic sites, was 98.5%. Concordance of IHC results, available in 39 of the 72 paired cases, was 94.9%. Only one case showed discordance between primary tumour and metastasis, being negative by both IHC and FISH in the primary and showing HER2 overexpression and amplification in the corresponding pancreatic lymph node metastasis. Conclusion: The high concordance observed between HER2 results obtained by both IHC and FISH on primary tumours and corresponding metastases suggests that in gastric cancer HER2 status is maintained in most cases unchanged during the metastatic process. Keywords: HER2, gastric cancer, FISH, immunohistochemistr