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American Journal of Botany May 2023Staminodes are commonly studied in hermaphroditic flowers, in which a fraction of the androecium evolves into infertile structures, but few studies have addressed the...
PREMISE
Staminodes are commonly studied in hermaphroditic flowers, in which a fraction of the androecium evolves into infertile structures, but few studies have addressed the evolution of staminodes as they occur through the loss of stamen function in carpellate flowers. Plants of Paronychia (Caryophyllaceae) are monoecious with hermaphroditic flowers with one staminodial whorl, except for the dioecious P. chartacea and P. minima. Dioecious species have carpellate flowers that evolved an additional whorl of staminodes, providing an exceptional opportunity to study a second origin of staminodes in the same flower.
METHODS
Using scanning electron microscopy, we observed the development of carpellate and staminate flowers to determine whether the developmental pathway of the staminodes in hermaphroditic flowers was co-opted during the evolutionary transition to unisexual flowers.
RESULTS
In carpellate flowers, antesepalous staminodes initiate as sterile anthers that develop similar to functioning stamens, but arrest before full development, leaving a rudimentary anther with lateral lobes that correspond to thecae. After antesepalous staminodes arrest, alternisepalous staminodes initiate as structures that correspond with filaments, as they do in staminate and hermaphroditic flowers.
CONCLUSIONS
The second origin of staminodes in carpellate flowers evolved using a different developmental pathway than what had previously evolved in the alternisepalous whorl. The two androecial whorls in the same flowers are serialogous as members of the androecium, but are paralogous as staminodes on the basis of structural and developmental differences.
Topics: Flowers; Microscopy, Electron, Scanning
PubMed: 37070618
DOI: 10.1002/ajb2.16171 -
Clinical Cancer Research : An Official... Sep 2023The FDA granted accelerated approval for amivantamab-vmjw (hereafter referred to as amivantamab), a bispecific antibody directed against EGFR and mesenchymal-epithelial... (Clinical Trial)
Clinical Trial
The FDA granted accelerated approval for amivantamab-vmjw (hereafter referred to as amivantamab), a bispecific antibody directed against EGFR and mesenchymal-epithelial transition receptor, on May 21, 2021, for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion mutations whose disease has progressed on or after platinum-based chemotherapy. Approval was based on results of an ongoing, multicenter, nonrandomized, open-label, multicohort clinical trial (CHRYSALIS, NCT02609776), demonstrating a substantial overall response rate (ORR) and durable responses, with an ORR of 40% [95% confidence interval (CI): 29-51] and a median response duration of 11.1 months (95% CI: 6.9-not evaluable). Guardant360 CDx was contemporaneously approved as a companion diagnostic for this indication to identify EGFR exon 20 insertion mutations in plasma specimens. The most notable safety finding was the high incidence (66%) of infusion-related reactions, which is addressed in both the Dosage and Administration and Warnings and Precautions sections of the product label. Other common adverse reactions (occurring in ≥20% of patients) were rash, paronychia, musculoskeletal pain, dyspnea, nausea and vomiting, fatigue, edema, stomatitis, cough, and constipation. The approval of amivantamab was the first approval of a targeted therapy for patients with advanced NSCLC harboring EGFR exon 20 insertion mutations.
Topics: Adult; Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Mutagenesis, Insertional; ErbB Receptors; Exons; Mutation; Protein Kinase Inhibitors
PubMed: 37022784
DOI: 10.1158/1078-0432.CCR-22-3713 -
Plants (Basel, Switzerland) Feb 2023All the names in described from South America are investigated. Five names (, subsp. var. , , , and ) are lecto- or neotypified on specimens preserved at GOET, K, LP,...
All the names in described from South America are investigated. Five names (, subsp. var. , , , and ) are lecto- or neotypified on specimens preserved at GOET, K, LP, and P. The typification of nine names, first proposed by Chaudhri in 1968 as the "holotype" are corrected according to Art. 9.10 of ICN. Three second-step typifications (Art. 9.17 of ICN) are proposed for , , and . The following nomenclatural changes are proposed: (basionym: subsp. var. ), (Philippi non Gray; Art. 53.1 of ICN), (basionym: subsp. var. ), subsp. (basionym: subsp. ), and subsp. (basionym: subsp. ). A new species () is proposed based on our examination of live plants and herbarium specimens. subsp. var. is synonymized () with . Finally, subsp. is excluded from South America since it was based on misidentified specimens (deposited at MO) of subsp. . A total of 30 species (43 taxa including subspecies, varieties, subvarieties, and forms) are recognized, highlighting that for some (, , ) we provisionally accept Chaudhri's infraspecific classification, since the high phenotypic variability of these taxa is quite complicated and further investigations need to solve their taxonomy.
PubMed: 36903924
DOI: 10.3390/plants12051064 -
International Journal of Environmental... Mar 2023There are a few reports that focus on radiotherapy (RT) and cetuximab (CET) therapy exclusively for oral cancer. This retrospective study aimed to investigate the...
There are a few reports that focus on radiotherapy (RT) and cetuximab (CET) therapy exclusively for oral cancer. This retrospective study aimed to investigate the efficacy and safety of RT and CET therapy for locally advanced (LA) or recurrent/metastatic (R/M) oral squamous cell carcinoma (OSCC). Seventy-nine patients from 13 hospitals who underwent RT and CET therapy for LA or R/M OSCC between January 2013 and May 2015 were enrolled in the study. Response, overall survival (OS), disease-specific survival (DSS), and adverse events were investigated. The completion rate was 62/79 (78.5%). The response rates in patients with LA and R/M OSCC were 69% and 37.8%, respectively. When only completed cases were examined, the response rates were 72.2% and 62.9%, respectively. The 1- and 2-year OS were 51.5% and 27.8%, respectively (median, 14 months), for patients with LA OSCC, and 41.5% and 11.9% (median, 10 months) for patients with R/M OSCC. The 1- and 2-year DSS were 61.8% and 33.4%, respectively (median, 17 months), for patients with LA OSCC, and 76.6% and 20.4% (median, 12 months) for patients with R/M OSCC. The most common adverse event was oral mucositis (60.8%), followed by dermatitis, acneiform rash, and paronychia. The completion rate was 85.7% in LA patients and 70.3% in R/M patients. The most common reason for noncompletion was an inadequate radiation dose due to worsening general conditions in R/M patients. Although the standard treatment for LA or R/M oral cancer is concomitant RT with high-dose cisplatin (CCRT) and the efficacy of RT and CET therapy for oral cancer is not considered to be as high as that for other head and neck cancers, it was thought that RT and CET therapy could be possible treatments for patients who cannot use high-dose cisplatin.
Topics: Humans; Cetuximab; Carcinoma, Squamous Cell; Cisplatin; Retrospective Studies; Japan; Mouth Neoplasms; Antineoplastic Combined Chemotherapy Protocols; Neoplasm Recurrence, Local; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms
PubMed: 36901553
DOI: 10.3390/ijerph20054545 -
Indian Journal of Sexually Transmitted... 2022Bowen's disease (BD) is a premalignant condition. Its exact etiology is unknown but chronic arsenic and sun exposure, and human papillomavirus infection is known...
Bowen's disease (BD) is a premalignant condition. Its exact etiology is unknown but chronic arsenic and sun exposure, and human papillomavirus infection is known predisposing factors. Pigmented lesions of BD represent 1.7%-5.5% of all BD cases. BD in the nail unit is challenging due to its varied clinical presentations such as fissure, ulceration, warty lesion, paronychia, onychocryptosis, and nail dystrophy. We present the case of a 43-year-old married, immunocompromised male (HIV), with a CD 4 count of 478, on tenofovir, atazanavir boosted with ritonavir regimen, known diabetic presented with multiple asymptomatic discrete, rounded, hyperpigmented verrucous papules on both surfaces of shaft of penis and scrotum and a single, 4 cm × 3 cm, irregular, smooth surfaced, hyperpigmented plaque, on the base of the penis extending to the upper part of the scrotum of 1-year duration with history of multiple unprotected sexual exposures with unknown female partners. Regional lymphadenopathy and systemic complaints were absent. Biopsy from hyperpigmented verrucous papule and hyperpigmented plaque was consistent with verruca vulgaris and pigmented Bowen's disease, respectively. The patient was lost to follow-up. Ten months later, he presented with longitudinal melanonychia with a subungual hyperpigmented mass protruding beyond the distal nail margin near the lateral nail fold of the right middle finger nail with an absent Hutchinson's sign. Longitudinal excisional biopsy of nail lesion was consistent with BD. He was started on 5-fluorouracil 5% for BD of genitals and podophyllin application for verruca vulgaris with remarkable improvement in both the lesions and there is no recurrence of nail lesion after 9 months of excision.
PubMed: 36743119
DOI: 10.4103/ijstd.ijstd_2_22 -
Cureus Dec 2022Nail changes elicited by Ibrutinib are relatively infrequent but are reported in the literature. Herein, we report on two cases that developed Ibrutinib-induced nail...
Nail changes elicited by Ibrutinib are relatively infrequent but are reported in the literature. Herein, we report on two cases that developed Ibrutinib-induced nail toxicities. A 63-year-old female, with relapsing mantle cell lymphoma on Ibrutinib 560mg/day for seven months developed paronychia, onychomadesis, Beau's lines, nail fragility, and brittleness over fingernails and toenails. On the other hand, an 80-year-old male with chronic lymphoid leukemia developed a bloody papule with hemorrhagic crust and nail-plate abnormalities. Skin toxicities manifested eight months after initiating Ibrutinib therapy. From a clinical perspective, Ibrutinib-induced chronic paronychia and PG have been established. All other PG triggers have been ruled out. After the cessation of Ibrutinib, the PG improved for both cases. The exact pathogenesis of PG induced by Ibrutinib is not yet understood but it had been compared to retinoid-related changes. Thus, further research and reporting of similar cases should be done to further understand the pathophysiology of such manifestations.
PubMed: 36712781
DOI: 10.7759/cureus.32943 -
Enfermedades Infecciosas Y... May 2023
Topics: Humans; Paronychia; Mpox (monkeypox); Anti-Bacterial Agents; Acute Disease
PubMed: 36710164
DOI: 10.1016/j.eimce.2022.09.011 -
Investigational New Drugs Feb 2023Potential novel strategies for adverse event (AE) management of osimertinib therapy, including therapeutic drug monitoring and the use of biomarkers, have not yet been... (Observational Study)
Observational Study
Population Pharmacokinetics, Pharmacogenomics, and Adverse Events of Osimertinib and its Two Active Metabolites, AZ5104 and AZ7550, in Japanese Patients with Advanced Non-small Cell Lung Cancer: a Prospective Observational Study.
BACKGROUND
Potential novel strategies for adverse event (AE) management of osimertinib therapy, including therapeutic drug monitoring and the use of biomarkers, have not yet been fully investigated. This study aimed to evaluate (1) the relationship between exposure to osimertinib, especially its active metabolites (AZ5104 and AZ7550), and AEs, and (2) the relationship between germline polymorphisms and AEs.
METHODS
We conducted a prospective, longitudinal observational study of 53 patients with advanced non-small cell lung cancer receiving osimertinib therapy from February 2019 to April 2022. A population pharmacokinetic model was developed to estimate the area under the serum concentration-time curve from 0 to 24 h (AUC) of osimertinib and its metabolites. Germline polymorphisms were analyzed using TaqMan® SNP genotyping and CycleavePCR® assays.
RESULTS
There was a significant association between the AUC of AZ7550 and grade ≥ 2 paronychia (p = 0.043) or anorexia (p = 0.011) and between that of osimertinib or AZ5104 and grade ≥ 2 diarrhea (p = 0.026 and p = 0.049, respectively). Furthermore, the AUC of AZ5104 was significantly associated with any grade ≥ 2 AEs (p = 0.046). EGFR rs2293348 and rs4947492 were associated with severe AEs (p = 0.019 and p = 0.050, respectively), and ABCG2 rs2231137 and ABCB1 rs1128503 were associated with grade ≥ 2 AEs (p = 0.008 and p = 0.038, respectively).
CONCLUSION
Higher exposures to osimertinib, AZ5104, and AZ7550 and polymorphisms in EGFR, ABCG2, and ABCB1 were related to higher severity of AEs; therefore, monitoring these may be beneficial for osimertinib AE management.
Topics: Humans; Aniline Compounds; Carcinoma, Non-Small-Cell Lung; East Asian People; ErbB Receptors; Lung Neoplasms; Mutation; Pharmacogenetics; Prospective Studies; Protein Kinase Inhibitors; ATP Binding Cassette Transporter, Subfamily B, Member 2; ATP Binding Cassette Transporter, Subfamily B
PubMed: 36637703
DOI: 10.1007/s10637-023-01328-9 -
BMC Medicine Jan 2023HL-085 is a selective, orally administered MEK1/2 inhibitor. We aimed to evaluate the safety and efficacy of HL-085 in patients with advanced melanoma harboring NRAS...
BACKGROUND
HL-085 is a selective, orally administered MEK1/2 inhibitor. We aimed to evaluate the safety and efficacy of HL-085 in patients with advanced melanoma harboring NRAS mutations.
METHODS
This was a multicenter phase 1 study. HL-085 was administered twice daily in a standard 3 + 3 dose-escalation design (10 dose cohorts; 0.5-18 mg twice daily), followed by dose expansion at the recommended phase II dose (RP2D). The primary endpoints included tolerability, dose-limiting toxicity (DLT), maximum tolerated dose (MTD) and RP2D.
RESULTS
Between September 13, 2017, and January 18, 2021, 42 patients were enrolled (dose escalation phase: n = 30; dose expansion phase: n = 12). No DLT was reported during dose escalation and MTD was not reached with HL-085 doses up to 18 mg twice daily. The RP2D was 12 mg twice daily. The most common all-grade drug-related adverse events (AEs) across all dose levels were rash (61.9%), increased creatine phosphokinase (CK, 59.5%), face edema (50.0%), increased aspartate aminotransferase (47.6%), peripheral edema (40.5%), diarrhea (33.3%), alanine aminotransferase (33.3%), and paronychia (19.0%), most of which were grade 1 and 2. Most frequency of grade ≥ 3 AEs were CK (14.2%), asthenia (7.1%), peripheral edema (4.8%), and acneiform dermatitis (4.8%). In the cohort of 12 mg twice daily dose (15 patients), confirmed objective response rate was 26.7%; disease control rate was 86.7%; median duration of response was 2.9 months; median progression-free survival was 3.6 months.
CONCLUSIONS
The HL-085 showed acceptable tolerability and substantial clinical activity in patients with advanced melanoma harboring NRAS mutations.
TRIAL REGISTRATION
Trial registration ClinicalTrials.gov number: NCT03973151.
Topics: Humans; Antineoplastic Agents; GTP Phosphohydrolases; Melanoma; Membrane Proteins; Mitogen-Activated Protein Kinase Kinases; Mutation; Progression-Free Survival; Protein Kinase Inhibitors
PubMed: 36600247
DOI: 10.1186/s12916-022-02669-7