Disease relevance of PFN2

• METHODS: Sixty-four patients with previously untreated, locoregionally advanced head and neck cancer received two cycles of cisplatin, bleomycin, and methotrexate (PBM) (33 patients) or cisplatin, fluorouracil (5-FU), and leucovorin (PFL) (31 patients) [1].
• Distant disease progression is 24% for PBM and only 3% for PFL [1].
• STUDY OBJECTIVE: To study the activity of continuous infusion cisplatin, 5-fluorouracil, and high-dose leucovorin (PFL) as induction chemotherapy in patients with previously untreated, advanced squamous cell carcinoma of the head and neck [2].
• CONCLUSION: PFL has significant activity with acceptable toxicity in patients with advanced disease who have a good performance status [3].
• The incidence of severe mucositis was reduced when GM-CSF was given in the second cycle of PFL [4].

High impact information on PFN2

• PFL was given to patients who were unable to receive bleomycin [1].
• Our findings strongly suggest that in brain profilin I and profilin II complexes link the actin cytoskeleton and endocytic membrane flow, directing actin and clathrin assembly to distinct membrane domains [5].
• In extracts from mouse brain, profilin I and profilin II can form complexes with regulators of endocytosis, synaptic vesicle recycling and actin assembly [5].
• We determined the structures of Acanthamoeba profilin I and profilin II by x-ray crystallography at resolutions of 2.0 and 2.8 A, respectively [6].
• Two areas of high positive potential on the surface of profilin II are candidate binding sites for phosphatidylinositol phosphates [6].

Chemical compound and disease context of PFN2

• Therefore, the addition of LV to cisplatin and 5-FU (PFL) may increase the activity of that combination in head and neck cancer [7].
• Neoadjuvant PFL augmented by methotrexate and piritrexim followed by concomitant chemoradiotherapy for advanced head and neck cancer: a feasible and active approach [8].
• A phase II clinical trial was initiated in 1987 to evaluate a new induction regimen of cis-platinum, 5-fluorouracil, and leucovorin (PFL) for patients with stages III-IV squamous cell carcinoma of the head and neck [9].
• PURPOSE: To determine the efficacy of the combination of cisplatin, fluorouracil, and high-dose l-leucovorin (PFL) as organ-preserving induction therapy followed by radiotherapy in untreated patients with advanced squamous cell carcinoma of the head and neck [10].

Biological context of PFN2

• The putative mouse homolog of PFN2 was mapped to mouse chromosome 3, thus suggesting a localization for the mouse homolog of USH3 [11].
• RESULTS: In the first cycle of PFL chemotherapy, GM-CSF significantly reduced the incidence, mean duration, and mean area under the curve (AUC) of severe oral gross mucositis (grade > or = 3) compared with no therapy [4].
• In the early stage, downregulation of collagens and keratins, together with upregulation of profilin 2 and ICAM-2, suggested cytoskeletal changes and cell adhesion remodeling [12].
• The objectives of this study were to establish the maximum tolerated dose of vinorelbine in combination with PFL, and to define the overall response rate in a cohort of patients treated with the maximum tolerated dose [13].
• In the present study, leachates of solid wastes from a polyfiber factory (PFL), an aeronautical plant (AEL), and a municipal sludge leachate (MSL) were assessed for their ability to induce DNA damage in human peripheral blood lymphocytes using the alkaline Comet assay [14].

Anatomical context of PFN2

• Northern blot analysis showed that profilin II is highly expressed in brain, skeletal muscle and kidney and less strongly in heart, placenta, lung and liver [15].
• A previously described antagonist of leukotriene-induced smooth muscle contraction PFL 55712 had a Ki of 23 +/- 2 nM as determined by competition binding experiments [16].
• Our results demonstrated that esophagectomy followed by concurrent irradiation and PFL combination chemotherapy may provide a significant improvement in the quality of life and survival for appropriate patients with advanced T4M0 epidermoid carcinoma of the esophagus [17].
• PATIENTS AND METHODS: This was a phase II study of PFL in 47 patients with resectable stage III (n = 20) and IV (n = 27) M0 squamous cell carcinoma of the head and neck, including larynx (n = 20), hypopharynx (n = 14), and oropharynx (n = 13) [10].

Associations of PFN2 with chemical compounds

• In contrast to serine 29 of profilin I, tyrosine 29 in profilin II is capable of forming an additional stacking interaction and a hydrogen bond with poly-L-proline which may account for the increased affinity of the second isoform for proline-rich peptides [18].
• Profilin-II labeled with rhodamine on cysteine at position 58 retains its affinity for actin, PIP(2) and poly-L-proline [19].
• Profilin I and profilin II have similar affinities for PtdIns(4,5)P2 and poly(L-proline), and both accelerate nucleotide exchange on monomeric actin to the same extent [20].
• CONCLUSION: Induction chemotherapy with PFL followed by concurrent cisplatin chemoradiotherapy is well tolerated and results in a good likelihood of organ preservation and excellent PFS and OS [21].
• Two-cycles (periods) of identical doses of cisplatin, fluorouracil (5-FU), and leucovorin (PFL) chemotherapy with cisplatin 20 mg/m2/d, 5-FU 800 mg/m2/d, leucovorin 90 mg/m2/d by 96-hour continuous intravenous infusion every 3 weeks were given to each patient [4].

Other interactions of PFN2

• The 115 differences detected again emphasized the abundance of neurons in the olfactory organ, especially a cluster of mRNAs encoding cytoskeletal-associated proteins and cell adhesion molecules such as 14-3-3zeta, actins, tubulins, trophinin, Fax, Yel077cp, suppressor of profilin 2, and gelsolin [22].

Analytical, diagnostic and therapeutic context of PFN2

• Here, we report the crystallization and X-ray structure determination of human profilin II to 2.2 A [18].
• CONCLUSIONS: The sequencing of induction chemotherapy and concomitant chemoradiotherapy is feasible and results in a high local control rate and in an encouraging survival rate with PFL [1].
• After PFL chemotherapy, GM-CSF 4 micrograms/kg subcutaneously from days 5 to 14 or no therapy was given by a randomized self-controlled crossover study design [4].
• BACKGROUND: To study prospectively the activity of primary chemotherapy with cisplatin, fluorouracil and leucovorin (PFL) in patients with paranasal cancer receiving surgery and postoperative radiotherapy [23].
• Multivariate Cox analysis showed PFL adjuvant chemotherapy was the independent factor that predicted metastasis-free survival after adjustment for other variables [24].

References