Virulence Profiles and Genome-Wide Association Study for Ascochyta lentis Isolates Collected from Australian Lentil-Growing Regions.

Ascochyta lentis, the causal organism of Ascochyta blight (AB) of lentil (Lens culinaris), has been shown to produce an avirulence effector protein that mediates AB resistance in certain lentil cultivars. The two known forms of the effector protein were identified from a biparental mapping population between isolates that have reciprocal virulence on 'PBA Hurricane XT' and 'Nipper'. The effector AlAvr1-1 was described for the PBA Hurricane XT-avirulent isolate P94-24 and AlAvr1-2 characterized in the PBA Hurricane XT-virulent isolate AlKewell. Here, we performed a genome-wide association study to identify other loci associated with AB for a differential set of lentil cultivars from a diverse panel of isolates collected in the Australian lentil-growing regions from 2013 to 2020. The chromosome 3 AlAvr1 locus was strongly associated with the PBA Hurricane XT, 'Indianhead', and Nipper disease responses, but one other genomic region on chromosome 11 was also associated with the Nipper disease trait. Our results corroborate earlier work that identified the AlAvr1 locus for field-collected isolates that span the period before release and after widespread adoption of PBA Hurricane XT. A multiplex PCR assay was developed to differentiate the genes AlAvr1-1 and AlAvr1-2 to predict PBA Hurricane XT avirulence and pathotype designation in the diversity panel. Increasing numbers of the PBA Hurricane XT-virulent pathotype 2 isolates across that time indicate strong selection for isolates with the AlAvr1-2 allele. Furthermore, one other region of the A. lentis genome may contribute to the pathogen-host interaction for lentil AB.

Comparing efficacy and safety of P013, a proposed pertuzumab biosimilar, with the reference product in HER2-positive breast cancer patients: a randomized, phase III, equivalency clinical trial.

BACKGROUND: Breast cancer is the most frequently diagnosed cancer and the leading reason for cancer-related death among women. Neoadjuvant treatment with dual-HER2 (human epidermal growth factor receptor 2) blockade has shown promising effects in this regard. The present study aimed to compare the efficacy and safety of a proposed pertuzumab biosimilar with the reference pertuzumab. METHODS: This randomized, phase III, multicenter, equivalency clinical trial was conducted on chemotherapy-naive women with HER2-positive breast cancer. Patients were randomly assigned (1:1) to receive six cycles of either P013 (CinnaGen, Iran) or the originator product (Perjeta, Roche, Switzerland) along with trastuzumab, carboplatin, and docetaxel every 3 weeks. Patients were stratified by cancer type (operable, locally advanced, inflammatory) and hormone receptor status. The primary endpoint was breast pathologic complete response (bpCR). Secondary endpoints included comparisons of total pCR, overall response rate (ORR), breast-conserving surgery (BCS), safety, and immunogenicity. RESULTS: Two hundred fourteen patients were randomized to treatment groups. bpCR rate in the per-protocol population was 67.62% in the P013 and 71.57% in the reference drug groups. Based on bpCR, P013 was equivalent to the reference pertuzumab with a mean difference of - 0.04 (95% CI: - 0.16, 0.09). Secondary endpoints were also comparable between the two groups. CONCLUSIONS: The proposed biosimilar P013 was equivalent to the reference product in terms of efficacy. The safety of both medications was also comparable.

Bevacizumab plus FOLFOX or FOLFIRI regimens on patients with unresectable liver-only metastases of metastatic colorectal cancer.

BACKGROUND: The present study was aimed to evaluate the efficacy and safety of at least three cycles of Bevacizumab in combination with chemotherapy regimens, FOLFIRI or FOLFOX to treat liver metastatic colorectal cancer and improved response rates in these patients. MATERIALS AND METHODS: In this non-randomized clinical trial, 38 patients were enrolled and followed for 12-weeks period of chemotherapy. Fifteen patients under treated with FOLOFX (Group I), 15 patients under treated with FOLOFIRI (Group II), 4 patients under treated with FOLOFX + Bevacizumab (Group III), and 34 patients under treated with FOLOFIRI + Bevacizumab (Group IV). Response to treatment was assessed in all patients as main endpoint. Patients in groups I and II, who did not response to treatment after 12 weeks of chemotherapy, were followed by groups III and IV regimens, respectively, for 12 weeks. RESULTS: Overall response rate was 35% (19 of 54), and complete response (CR), partial response (PR), progressive disease (PD), and stable disease (SD) rates in all patients were 18%, 17%, 35%, and 30%. PR, SD, and PD were different among groups, but no statistical significance was noted among groups (P-value >0.05). No patient achieved a CR in groups III and IV, although CR was observed in 4 patients (27%) and 6 patients (40%) in groups I and II, respectively. The rare of CR was statistically significant among studied groups (P-value = 0.013). CONCLUSION: Results showed that adding Bevacizumab to chemotherapy regimens, in patients who did not response to FOLFIRI or FOLFOX regimen, did not increase CR in these patients.

Incidence and clinical importance of BCR-ABL1 mutations in Iranian patients with chronic myeloid leukemia on imatinib.

Mutations of the BCR-ABL1 kinase domain seem to be the most common cause of imatinib mesylate resistance in chronic myeloid leukemia (CML). We screened BCR-ABL1 kinase domain mutations using nested reverse transcriptase polymerase chain reaction and direct sequencing in 30 CML patients including 22 resistant patients and 8 patients with optimal response to imatinib. Three mutations of two different types were identified in 3 of 22 (13.6%) resistant patients. Two patients had p.E355G mutation in the catalytic domain, and the third patient had p.G398R in the activation loop that is reported here for the first time. No mutation was found in patients with optimal response to imatinib. The frequency of mutations was similar in patients with primary resistance compared with patients with secondary resistance (25 vs 11%; P=1). Mutation status had no impact on the overall survival and progression-free survival. p.E355G mutation was correlated with shorter survival (P=0.047) in resistant patients. We conclude that BCR- ABL1 mutations are associated with the clinical resistance, but may not be considered the only cause of resistance to imatinib. Mutational analysis may identify resistant patients at risk of disease progression.