%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Víctor Alfonso Solarte, Paulette Conget, Jean-Paul Vernot, Jaiver Eduardo Rosas, Zuly Jenny Rivera, Javier Eduardo García, Martha Ligia Arango-Rodríguez
A tetrameric peptide derived from bovine lactoferricin as a potential therapeutic tool for oral squamous cell carcinoma: A preclinical model
www.plosone.org
www.plosone.org
endstream
endobj
3 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 14 0 R/Annots 15 0 R/Contents 16 0 R/TrimBox[0 0 612 792]>>
endobj
15 0 obj
[17 0 R 18 0 R 19 0 R 20 0 R 21 0 R 22 0 R 23 0 R 24 0 R 25 0 R 26 0 R 27 0 R 28 0 R 29 0 R 30 0 R 31 0 R 32 0 R 33 0 R 34 0 R 35 0 R 36 0 R 37 0 R 38 0 R 39 0 R 40 0 R 41 0 R 42 0 R 43 0 R 44 0 R 45 0 R 46 0 R 47 0 R 48 0 R 49 0 R]
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref001)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref002)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref003)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref004)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref005)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref006)>>
endobj
23 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref010)>>
endobj
24 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref011)>>
endobj
25 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref016)>>
endobj
26 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref010)>>
endobj
27 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref017)>>
endobj
28 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref018)>>
endobj
29 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref019)>>
endobj
30 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref020)>>
endobj
31 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref021)>>
endobj
32 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref023)>>
endobj
33 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref023)>>
endobj
34 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref023)>>
endobj
35 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref024)>>
endobj
36 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref007)>>
endobj
37 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref014)>>
endobj
38 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref015)>>
endobj
39 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref018)>>
endobj
40 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref025)>>
endobj
41 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref027)>>
endobj
42 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref023)>>
endobj
43 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref028)>>
endobj
44 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref029)>>
endobj
45 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref029)>>
endobj
46 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref007)>>
endobj
47 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.t001)>>
endobj
48 0 obj
<>/Border[0 0 0]/Dest(Rpone.0174707.ref030)>>
endobj
49 0 obj
<>/Border[0 0 0]/A 50 0 R>>
endobj
50 0 obj
<>
endobj
16 0 obj
[51 0 R 52 0 R 53 0 R 54 0 R 55 0 R 56 0 R 57 0 R 58 0 R 59 0 R 60 0 R 61 0 R 62 0 R 63 0 R 64 0 R 65 0 R 66 0 R 67 0 R 68 0 R 69 0 R 70 0 R 71 0 R 72 0 R 73 0 R 74 0 R 75 0 R 76 0 R 77 0 R 78 0 R 79 0 R]
endobj
51 0 obj
<>stream
q
0.83 0.64 0.02 0 k
407.8488 674.9858 m
412.611 674.9858 l
h
f*
355.011 649.0205 m
359.7732 649.0205 l
h
f*
276.7748 622.9984 m
281.537 622.9984 l
h
f*
452.0693 610.0157 m
456.8315 610.0157 l
h
f*
461.2535 610.0157 m
466.0157 610.0157 l
h
f*
465.4488 571.011 m
470.211 571.011 l
h
f*
475.3701 571.011 m
484.8945 571.011 l
h
f*
410.5134 558.0283 m
420.0378 558.0283 l
h
f*
425.1969 558.0283 m
434.7213 558.0283 l
h
f*
411.2504 544.989 m
420.7748 544.989 l
h
f*
425.1402 544.989 m
434.6646 544.989 l
h
f*
439.0299 544.989 m
448.5543 544.989 l
h
f*
485.2346 505.9843 m
494.7591 505.9843 l
h
f*
483.137 493.0016 m
492.6614 493.0016 l
h
f*
359.7165 453.9969 m
369.2409 453.9969 l
h
f*
374.4567 453.9969 m
383.9244 453.9969 l
h
f*
543.2882 453.9969 m
552.8126 453.9969 l
h
f*
513.1276 414.9921 m
522.652 414.9921 l
h
f*
527.074 414.9921 m
536.5984 414.9921 l
h
f*
221.726 363.0047 m
226.4882 363.0047 l
h
f*
230.9669 363.0047 m
240.4913 363.0047 l
h
f*
244.9134 363.0047 m
254.4378 363.0047 l
h
f*
258.9165 363.0047 m
268.3843 363.0047 l
h
f*
272.863 363.0047 m
282.3874 363.0047 l
h
f*
287.5465 363.0047 m
297.0709 363.0047 l
h
f*
203.4142 324 m
212.9386 324 l
h
f*
217.3606 324 m
226.885 324 l
h
f*
231.3071 324 m
240.8315 324 l
h
f*
457.3984 284.9953 m
466.9228 284.9953 l
h
f*
451.5024 272.0126 m
456.2079 272.0126 l
h
f*
308.9764 146.948 m
338.1165 146.948 l
h
f*
283.5213 133.9087 m
293.0457 133.9087 l
h
f*
0 g
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 706.0535 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Introduction)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 689.1023 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Oral)Tj
2.0182 0 Td
(squamous)Tj
4.2633 0 Td
(cell)Tj
1.559 0 Td
(carcinoma)Tj
4.4504 0 Td
(\(OSCC\),)Tj
3.6737 0 Td
(one)Tj
1.7008 0 Td
(of)Tj
1.0147 0 Td
(the)Tj
1.4684 0 Td
(ten)Tj
1.491 0 Td
(most)Tj
2.2053 0 Td
(common)Tj
3.8438 0 Td
(cancers)Tj
3.2031 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(world,)Tj
-33.3975 -1.3039 Td
(has)Tj
1.542 0 Td
(a)Tj
0.652 0 Td
(delayed)Tj
3.2598 0 Td
(clinical)Tj
3.0727 0 Td
(detection)Tj
3.9401 0 Td
(and)Tj
1.7292 0 Td
(poor)Tj
2.1259 0 Td
(prognosis)Tj
4.1216 0 Td
([)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
(].)Tj
1.6044 0 Td
(The)Tj
1.7801 0 Td
(treatment)Tj
4.1329 0 Td
(of)Tj
1.0205 0 Td
(this)Tj
1.6724 0 Td
(pathology)Tj
4.1783 0 Td
(fre-)Tj
-34.8319 -1.2982 Td
(quently)Tj
3.2258 0 Td
(requires)Tj
3.4695 0 Td
(combined)Tj
4.2463 0 Td
(therapies:)Tj
4.0705 0 Td
(surgery)Tj
3.1918 0 Td
(as)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(primary)Tj
3.4582 0 Td
(modality,)Tj
4.0025 0 Td
(and)Tj
1.7291 0 Td
(radiotherapy)Tj
5.3518 0 Td
(and)Tj
-35.2287 -1.2983 Td
(chemotherapy)Tj
5.947 0 Td
(as)Tj
1.0148 0 Td
(adjuvant)Tj
3.702 0 Td
(treatments)Tj
4.4957 0 Td
([)Tj
0.83 0.64 0.02 0 k
(2)Tj
0 g
(].)Tj
1.6044 0 Td
(However,)Tj
4.0762 0 Td
(there)Tj
2.2621 0 Td
(is)Tj
0.8504 0 Td
(limited)Tj
3.067 0 Td
(success)Tj
3.1011 0 Td
(associated)Tj
4.2576 0 Td
(with)Tj
-34.3783 -1.3039 Td
(the)Tj
1.4683 0 Td
(use)Tj
1.5307 0 Td
(of)Tj
1.0148 0 Td
(these)Tj
2.2563 0 Td
(therapies,)Tj
4.0706 0 Td
(and)Tj
1.7291 0 Td
(patients)Tj
3.3675 0 Td
(report)Tj
2.7099 0 Td
(a)Tj
0.652 0 Td
(variety)Tj
2.9253 0 Td
(of)Tj
1.0148 0 Td
(severe)Tj
2.6759 0 Td
(side)Tj
1.7972 0 Td
(effects)Tj
2.7269 0 Td
(caused)Tj
2.9197 0 Td
(by)Tj
1.1792 0 Td
(the)Tj
1.4683 0 Td
(lack)Tj
-35.5065 -1.2983 Td
(of)Tj
1.0147 0 Td
(drug)Tj
2.109 0 Td
(specificity)Tj
4.2123 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(].)Tj
1.6044 0 Td
(In)Tj
1.1055 0 Td
(the)Tj
1.4683 0 Td
(face)Tj
1.7915 0 Td
(of)Tj
1.0148 0 Td
(these)Tj
2.2507 0 Td
(facts,)Tj
2.2507 0 Td
(researchers)Tj
4.7111 0 Td
(have)Tj
2.0636 0 Td
(proposed)Tj
3.9515 0 Td
(alternative)Tj
4.4164 0 Td
(thera-)Tj
-33.9645 -1.2982 Td
(peutic)Tj
2.6758 0 Td
(approaches)Tj
4.7395 0 Td
(in)Tj
1.0318 0 Td
(order)Tj
2.4208 0 Td
(to)Tj
1.0261 0 Td
(improve)Tj
3.583 0 Td
(the)Tj
1.4684 0 Td
(treatment)Tj
4.1328 0 Td
(of)Tj
1.0148 0 Td
(OSCC)Tj
2.7723 0 Td
([)Tj
0.83 0.64 0.02 0 k
(4)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2586 0 Td
(5)Tj
0 g
(].)Tj
1.2642 0 Td
(For)Tj
1.6214 0 Td
(instance,)Tj
3.7531 0 Td
(cationic)Tj
-32.7626 -1.304 Td
(amphipathic)Tj
5.2497 0 Td
(peptides)Tj
3.5603 0 Td
(\(CAPs\))Tj
3.1634 0 Td
(have)Tj
2.0636 0 Td
(shown)Tj
2.846 0 Td
(to)Tj
1.0261 0 Td
(be)Tj
1.1509 0 Td
(a)Tj
0.652 0 Td
(novel)Tj
2.4037 0 Td
(promising)Tj
4.3427 0 Td
(tool)Tj
1.7801 0 Td
(for)Tj
1.3833 0 Td
(treating)Tj
3.3279 0 Td
(different)Tj
-32.9497 -1.2982 Td
(types)Tj
2.2733 0 Td
(of)Tj
1.0148 0 Td
(cancer.)Tj
3.0728 0 Td
(Several)Tj
3.0443 0 Td
(studies)Tj
2.9877 0 Td
(have)Tj
2.058 0 Td
(described)Tj
4.0535 0 Td
(their)Tj
2.109 0 Td
(selectivity)Tj
4.1385 0 Td
(and)Tj
1.7291 0 Td
(cytotoxic)Tj
3.8665 0 Td
(activity)Tj
3.1181 0 Td
(in)Tj
1.0318 0 Td
(a)Tj
0.6576 0 Td
(wide)Tj
-35.155 -1.2983 Td
(range)Tj
2.4604 0 Td
(of)Tj
1.0148 0 Td
(tumors)Tj
3.1068 0 Td
(using)Tj
2.3867 0 Td
(different)Tj
/F11 1 Tf
3.6567 0 Td
[()12()]TJ
1.0148 0 Td
[()-13()14()7()20()]TJ
/F7 1 Tf
2.0466 0 Td
(and)Tj
/F11 1 Tf
1.7291 0 Td
[()12()]TJ
1.0148 0 Td
[()-13()15()3()]TJ
/F7 1 Tf
1.8198 0 Td
(cancer)Tj
2.846 0 Td
(models)Tj
3.1067 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(].)Tj
3.0671 0 Td
(These)Tj
2.5682 0 Td
(studies)Tj
2.9877 0 Td
(indi-)Tj
-34.8262 -1.2983 Td
(cate)Tj
1.7971 0 Td
(that)Tj
1.7802 0 Td
(CAPs)Tj
2.4888 0 Td
(are)Tj
1.4456 0 Td
(likely)Tj
2.3528 0 Td
(to)Tj
1.0261 0 Td
(trigger)Tj
2.8856 0 Td
(fewer)Tj
2.4095 0 Td
(side)Tj
1.7971 0 Td
(effects)Tj
2.7269 0 Td
([)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(16)Tj
0 g
(])Tj
3.3222 0 Td
(as)Tj
1.0148 0 Td
(well)Tj
1.8199 0 Td
(as)Tj
1.0147 0 Td
(induce)Tj
2.9367 0 Td
(immunogenic)Tj
-30.818 -1.3039 Td
(cell)Tj
1.5477 0 Td
(death,)Tj
2.6475 0 Td
(which)Tj
2.6419 0 Td
(in)Tj
1.0261 0 Td
(turn)Tj
1.9616 0 Td
(prevents)Tj
3.6056 0 Td
(cancer)Tj
2.8346 0 Td
(recurrence)Tj
4.5184 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7292 0 Td
(17)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.3889 0 Td
(18)Tj
0 g
(])Tj
1.5024 0 Td
(and)Tj
1.7234 0 Td
(therefore,)Tj
4.0706 0 Td
(represents)Tj
4.3086 0 Td
(a)Tj
0.6463 0 Td
(sig-)Tj
-36.1528 -1.2982 Td
(nificant)Tj
3.2938 0 Td
(advance)Tj
3.4639 0 Td
(towards)Tj
3.4072 0 Td
(more)Tj
2.3414 0 Td
(efficient)Tj
3.4469 0 Td
(cancer)Tj
2.846 0 Td
(treatments.)Tj
4.7168 0 Td
(Moreover,)Tj
4.3994 0 Td
(additional)Tj
4.2746 0 Td
(studies)Tj
2.9877 0 Td
(have)Tj
-35.1777 -1.2983 Td
(revealed)Tj
3.5206 0 Td
(that)Tj
1.7801 0 Td
(the)Tj
1.4683 0 Td
(high)Tj
2.0126 0 Td
(content)Tj
3.2655 0 Td
(of)Tj
1.0148 0 Td
(cationic)Tj
3.3902 0 Td
(and)Tj
1.7292 0 Td
(hydrophobic)Tj
5.3574 0 Td
(amino)Tj
2.7949 0 Td
(acids)Tj
2.2337 0 Td
(in)Tj
1.0375 0 Td
(CAPs,)Tj
2.7099 0 Td
(such)Tj
2.0636 0 Td
(as)Tj
1.0148 0 Td
(argi-)Tj
-35.3931 -1.3039 Td
(nine)Tj
2.0069 0 Td
(and)Tj
1.7291 0 Td
(tryptophan,)Tj
4.9209 0 Td
(are)Tj
1.4513 0 Td
(critical)Tj
2.948 0 Td
(for)Tj
1.389 0 Td
(their)Tj
2.1033 0 Td
(antitumoral)Tj
4.9719 0 Td
(selective)Tj
3.5433 0 Td
(activity)Tj
3.1181 0 Td
([)Tj
0.83 0.64 0.02 0 k
(19)Tj
0 g
(].)Tj
2.075 0 Td
(Specifically,)Tj
4.9152 0 Td
(these)Tj
-35.172 -1.2983 Td
(peptides)Tj
3.5546 0 Td
(are)Tj
1.4513 0 Td
(prone)Tj
2.5852 0 Td
(to)Tj
1.0261 0 Td
(interaction)Tj
4.6035 0 Td
(with)Tj
2.0012 0 Td
(anionic)Tj
3.2145 0 Td
(cell)Tj
1.559 0 Td
(membrane)Tj
4.5694 0 Td
(surfaces)Tj
3.4073 0 Td
([)Tj
0.83 0.64 0.02 0 k
(20)Tj
0 g
(],)Tj
2.0749 0 Td
(which)Tj
2.6532 0 Td
(are)Tj
1.4457 0 Td
(charac-)Tj
-34.1459 -1.2982 Td
(teristic)Tj
2.931 0 Td
(of)Tj
1.0148 0 Td
(cancer)Tj
2.8402 0 Td
(cells:)Tj
2.1487 0 Td
(they)Tj
1.9219 0 Td
(have)Tj
2.0636 0 Td
(more)Tj
2.3414 0 Td
(anionic)Tj
3.2145 0 Td
(molecules)Tj
4.1952 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.474 0 Td
(surface)Tj
3.0444 0 Td
(than)Tj
2.0296 0 Td
(non-cancerous)Tj
-30.4949 -1.304 Td
(cells.)Tj
2.1429 0 Td
(In)Tj
1.1112 0 Td
(addition,)Tj
3.8211 0 Td
(such)Tj
2.0579 0 Td
(anionic)Tj
3.2202 0 Td
(molecules)Tj
4.1952 0 Td
(are)Tj
1.4513 0 Td
(associated)Tj
4.2576 0 Td
(with)Tj
1.9956 0 Td
(phosohatidylserine,)Tj
8.0164 0 Td
(lipoproteins)Tj
-32.2694 -1.2982 Td
(O-glycocylated)Tj
6.2191 0 Td
(mucines)Tj
3.5943 0 Td
(and)Tj
1.7292 0 Td
(sialic)Tj
2.2166 0 Td
(acid)Tj
1.8709 0 Td
([)Tj
0.83 0.64 0.02 0 k
(21)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(],)Tj
3.5489 0 Td
(and)Tj
1.7292 0 Td
(allow)Tj
2.3357 0 Td
(the)Tj
1.474 0 Td
(peptides)Tj
3.5546 0 Td
(to)Tj
1.0262 0 Td
(be)Tj
1.1508 0 Td
(selective)Tj
3.5376 0 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(].)Tj
-33.9871 -1.2983 Td
(Regarding)Tj
4.3426 0 Td
(CAPs,)Tj
2.7156 0 Td
(their)Tj
2.1033 0 Td
(anticancer)Tj
4.3936 0 Td
(mechanism)Tj
4.8473 0 Td
(of)Tj
1.0148 0 Td
(action)Tj
2.6985 0 Td
(is)Tj
0.8447 0 Td
(suggested)Tj
4.0762 0 Td
(to)Tj
1.0262 0 Td
(be)Tj
1.1452 0 Td
(the)Tj
1.474 0 Td
(induction)Tj
4.1328 0 Td
(of)Tj
1.0148 0 Td
(cell)Tj
-35.8296 -1.2983 Td
(necrosis)Tj
3.4809 0 Td
(\(via)Tj
1.7178 0 Td
(cell)Tj
1.559 0 Td
(membrane)Tj
4.5638 0 Td
(lysis\))Tj
2.2506 0 Td
(or)Tj
1.0999 0 Td
(cell)Tj
1.559 0 Td
(apoptosis)Tj
3.9912 0 Td
(\(via)Tj
1.7178 0 Td
(slight)Tj
2.3811 0 Td
(damage)Tj
3.3278 0 Td
(to)Tj
1.0205 0 Td
(the)Tj
1.474 0 Td
(plasma)Tj
3.0274 0 Td
(membrane)Tj
-33.1708 -1.3039 Td
(or)Tj
1.0941 0 Td
(the)Tj
1.474 0 Td
(mitochondrial)Tj
5.9641 0 Td
(lytic)Tj
1.9105 0 Td
(effect\),)Tj
2.931 0 Td
(which)Tj
2.6476 0 Td
(depend)Tj
3.1918 0 Td
(on)Tj
1.2755 0 Td
(the)Tj
1.4684 0 Td
(peptide)Tj
3.1918 0 Td
(concentration)Tj
5.8223 0 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(24)Tj
0 g
(].)Tj
-31.5097 -1.2982 Td
(Bovine)Tj
3.0047 0 Td
(Lactoferricin)Tj
5.3801 0 Td
(\(LfcinB\))Tj
3.5433 0 Td
(is)Tj
0.8504 0 Td
(one)Tj
1.7007 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(most)Tj
2.2053 0 Td
(studied)Tj
3.1521 0 Td
(CAPs.)Tj
2.7156 0 Td
(Different)Tj
3.8608 0 Td
(amphipathic)Tj
-30.0924 -1.2983 Td
(peptides)Tj
3.5546 0 Td
(have)Tj
2.0579 0 Td
(been)Tj
2.126 0 Td
(derived)Tj
3.2145 0 Td
(from)Tj
2.2053 0 Td
(its)Tj
1.1452 0 Td
(sequence)Tj
3.8607 0 Td
(and)Tj
1.7292 0 Td
(have)Tj
2.0579 0 Td
(shown)Tj
2.8516 0 Td
(high)Tj
2.007 0 Td
(selective)Tj
3.5432 0 Td
(cytotoxicity)Tj
-30.3531 -1.3039 Td
(against)Tj
3.0273 0 Td
(various)Tj
3.1408 0 Td
(types)Tj
2.2734 0 Td
(of)Tj
1.0204 0 Td
(cancer,)Tj
3.0671 0 Td
(such)Tj
2.0579 0 Td
(as)Tj
1.0148 0 Td
(hematological)Tj
5.8224 0 Td
(malignancies,)Tj
5.6806 0 Td
(melanomas,)Tj
5.0399 0 Td
(and)Tj
1.7292 0 Td
(carcino-)Tj
-33.8738 -1.2983 Td
(mas)Tj
1.8311 0 Td
([)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2643 0 Td
(14)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.3946 0 Td
(15)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.4003 0 Td
(18)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.3946 0 Td
(25)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(27)Tj
0 g
(].)Tj
3.2032 0 Td
(In)Tj
1.1111 0 Td
(particular,)Tj
4.337 0 Td
(several)Tj
2.931 0 Td
(studies)Tj
2.9877 0 Td
(have)Tj
2.058 0 Td
(reported)Tj
3.6623 0 Td
(that)Tj
1.7802 0 Td
(the)Tj
1.4683 0 Td
(core)Tj
1.9445 0 Td
(sequence)Tj
-32.7682 -1.2983 Td
(20-RRWQWR-25)Tj
7.3643 0 Td
(\(LfcinB\(2025\)\))Tj
6.6444 0 Td
(of)Tj
1.0148 0 Td
(LfcinB)Tj
2.8686 0 Td
(is)Tj
0.8447 0 Td
(the)Tj
1.4684 0 Td
(responsible)Tj
4.7565 0 Td
(motif)Tj
2.3981 0 Td
(for)Tj
1.3889 0 Td
(the)Tj
1.4684 0 Td
(selective)Tj
3.5433 0 Td
(cytotoxic)Tj
-33.7604 -1.3039 Td
(activity)Tj
3.118 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(peptide,)Tj
3.4185 0 Td
(due)Tj
1.7008 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4684 0 Td
(well-defined)Tj
5.176 0 Td
(amphipathic)Tj
5.2554 0 Td
(structure)Tj
3.8211 0 Td
(that)Tj
1.7801 0 Td
(the)Tj
1.4684 0 Td
(peptide)Tj
3.1974 0 Td
(adopts)Tj
-33.9134 -1.2982 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7347 0 Td
(28)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.3947 0 Td
(29)Tj
0 g
(].)Tj
-1.9332 -1.2983 Td
(We)Tj
1.61 0 Td
(have)Tj
2.0636 0 Td
(recently)Tj
3.4073 0 Td
(demonstrated)Tj
5.7599 0 Td
(that)Tj
1.7802 0 Td
(peptides)Tj
3.5546 0 Td
(derived)Tj
3.2145 0 Td
(from)Tj
2.2053 0 Td
(LfcinB\(2025\))Tj
5.9697 0 Td
(exhibited)Tj
3.9232 0 Td
(a)Tj
0.6576 0 Td
(spe-)Tj
-35.3421 -1.3039 Td
(cific)Tj
1.8878 0 Td
(cytotoxic)Tj
3.8664 0 Td
(effect)Tj
2.3641 0 Td
(in)Tj
1.0318 0 Td
(tumorigenic)Tj
5.142 0 Td
(cell)Tj
1.5591 0 Td
(lines.)Tj
2.2904 0 Td
(Specifically,)Tj
4.9152 0 Td
(the)Tj
1.4683 0 Td
(tetrameric)Tj
4.3484 0 Td
(peptide)Tj
3.1974 0 Td
(LfcinB\(20)Tj
-32.0709 -1.2983 Td
(25\))Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 212.9385 284.4283 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(4)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 216.4535 286.0724 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(,)Tj
0.4478 0 Td
(containing)Tj
4.5298 0 Td
(four)Tj
1.9105 0 Td
(molecules)Tj
4.2009 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(monomer)Tj
4.218 0 Td
(LfcinB\(2025\))Tj
5.964 0 Td
([)Tj
0.83 0.64 0.02 0 k
(29)Tj
0 g
(],)Tj
2.075 0 Td
(caused)Tj
2.9196 0 Td
(a)Tj
0.652 0 Td
(more)Tj
2.3414 0 Td
(selective)Tj
-33.3861 -1.2982 Td
(cytotoxic)Tj
3.8606 0 Td
(effect)Tj
2.3698 0 Td
(on)Tj
1.2756 0 Td
(OSCC)Tj
2.7666 0 Td
(cells)Tj
1.9218 0 Td
(by)Tj
1.1792 0 Td
(activating)Tj
4.1103 0 Td
(a)Tj
0.6576 0 Td
(necrotic)Tj
3.4809 0 Td
(process)Tj
3.1861 0 Td
([)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(].)Tj
1.5988 0 Td
(Based)Tj
2.5455 0 Td
(on)Tj
1.2755 0 Td
(these)Tj
2.2564 0 Td
(findings,)Tj
3.719 0 Td
(the)Tj
-36.2037 -1.2983 Td
(present)Tj
3.1633 0 Td
(work)Tj
2.2791 0 Td
(evaluated)Tj
3.9911 0 Td
(the)Tj
1.4683 0 Td
(antitumoral)Tj
4.972 0 Td
(effect)Tj
2.3641 0 Td
(of)Tj
1.0148 0 Td
(LfcinB\(2025\))Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 449.9716 258.4062 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(4)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 455.7543 260.107 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(on)Tj
1.2755 0 Td
(a)Tj
0.652 0 Td
(preclinical)Tj
4.388 0 Td
(OSCC)Tj
2.7723 0 Td
(model)Tj
-34.6618 -1.3039 Td
(generated)Tj
4.1329 0 Td
(in)Tj
1.0375 0 Td
(Syrian)Tj
2.7723 0 Td
(golden)Tj
2.9366 0 Td
(hamsters,)Tj
4.0422 0 Td
(in)Tj
1.0375 0 Td
(order)Tj
2.4208 0 Td
(to)Tj
1.0261 0 Td
(establish)Tj
3.6453 0 Td
(its)Tj
1.1452 0 Td
(potential)Tj
3.7586 0 Td
(use)Tj
1.5307 0 Td
(as)Tj
1.0148 0 Td
(a)Tj
0.6577 0 Td
(tool)Tj
1.7744 0 Td
(for)Tj
1.389 0 Td
(human)Tj
-34.3216 -1.2982 Td
(OSCC)Tj
2.7666 0 Td
(treatment.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 195.9874 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Materials)Tj
4.5071 0 Td
(and)Tj
1.989 0 Td
(methods)Tj
/F0 1 Tf
-6.4961 -1.4976 Td
(Peptide)Tj
3.5669 0 Td
(synthesis,)Tj
4.6205 0 Td
(purity)Tj
2.6363 0 Td
(and)Tj
1.8661 0 Td
(characterization)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 161.0078 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(The)Tj
1.7801 0 Td
(linear)Tj
2.5115 0 Td
(form)Tj
2.2053 0 Td
(of)Tj
1.0148 0 Td
(LfcinB)Tj
2.8687 0 Td
(\(LfcinB25\),)Tj
4.7168 0 Td
(the)Tj
1.474 0 Td
(monomeric)Tj
4.9039 0 Td
(\(LfcinB\(2025\)\))Tj
6.6444 0 Td
(and)Tj
1.7348 0 Td
(the)Tj
1.4683 0 Td
(tetrameric)Tj
-31.3226 -1.2982 Td
(\(LfcinB\(2025\))Tj
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 260.844 146.3244 cm
BT
/F7 1 Tf
1 TL
-0.0053 Tc
0 0 Td
(4)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 264.4157 148.0251 cm
BT
/F7 1 Tf
1 TL
-0.004 Tc
0 0 Td
(\))Tj
0.5612 0 Td
(peptides)Tj
3.5546 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(Table)Tj
2.7836 0 Td
(1)Tj
0 g
(\))Tj
1.0318 0 Td
(were)Tj
2.126 0 Td
(synthesized)Tj
4.8245 0 Td
(using)Tj
2.3868 0 Td
(the)Tj
1.474 0 Td
(SPPS-Fmoc/tBu)Tj
6.65 0 Td
(method,)Tj
3.549 0 Td
(as)Tj
-35.3817 -1.3039 Td
(previously)Tj
4.3483 0 Td
(reported)Tj
3.6622 0 Td
([)Tj
0.83 0.64 0.02 0 k
(30)Tj
0 g
(].)Tj
2.075 0 Td
(The)Tj
1.7801 0 Td
(purity)Tj
2.6589 0 Td
(\()Tj
/F12 1 Tf
0 Tc
(>)Tj
/F7 1 Tf
-0.004 Tc
(90%\))Tj
3.3789 0 Td
(and)Tj
1.7348 0 Td
(the)Tj
1.4683 0 Td
(molecular)Tj
4.2179 0 Td
(weight)Tj
2.8857 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(peptides)Tj
3.5546 0 Td
(were)Tj
-34.2478 -1.2982 Td
(determined)Tj
4.8472 0 Td
(via)Tj
1.3776 0 Td
(RP-HPLC)Tj
4.2802 0 Td
(analysis)Tj
3.3279 0 Td
(and)Tj
1.7291 0 Td
(MS)Tj
1.5874 0 Td
(MALDI-TOF,)Tj
5.8733 0 Td
(respectively.)Tj
5.108 0 Td
(Peptides)Tj
3.6 0 Td
(used)Tj
2.0579 0 Td
(for)Tj
/F11 1 Tf
1.389 0 Td
[()12()]TJ
-35.1776 -1.2983 Td
[()-13()15()3()]TJ
/F7 1 Tf
1.8198 0 Td
(experiments)Tj
5.1363 0 Td
(were)Tj
2.1259 0 Td
(dissolved)Tj
3.8948 0 Td
(in)Tj
1.0375 0 Td
(0.9%)Tj
2.1486 0 Td
(sodium)Tj
3.2315 0 Td
(chloride)Tj
3.5149 0 Td
(solution)Tj
3.481 0 Td
(at)Tj
0.9524 0 Td
(100,)Tj
1.8765 0 Td
(200,)Tj
1.8709 0 Td
(and)Tj
1.7291 0 Td
(300)Tj
/F13 1 Tf
1.6497 0 Td
[()]TJ
/F7 1 Tf
(g/mL,)Tj
-34.4689 -1.3039 Td
(while)Tj
2.3697 0 Td
(peptides)Tj
3.5546 0 Td
(used)Tj
2.0579 0 Td
(for)Tj
/F11 1 Tf
1.389 0 Td
[()12()]TJ
1.0148 0 Td
[()-13()14()7()20()]TJ
/F7 1 Tf
2.0409 0 Td
(assays)Tj
2.6305 0 Td
(were)Tj
2.1203 0 Td
(dissolved)Tj
3.8948 0 Td
(in)Tj
1.0375 0 Td
(culture)Tj
3.0387 0 Td
(medium)Tj
3.6056 0 Td
(without)Tj
3.3279 0 Td
(fetal)Tj
1.9105 0 Td
(bovine)Tj
-33.9927 -1.2983 Td
(serum)Tj
2.7212 0 Td
(\(FBS\),)Tj
2.7099 0 Td
(at)Tj
0.9525 0 Td
(a)Tj
0.6518 0 Td
(concentration)Tj
5.8223 0 Td
(of)Tj
1.0148 0 Td
(100)Tj
/F13 1 Tf
1.6441 0 Td
[()]TJ
/F7 1 Tf
(g/mL.)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 107.1496 23.6976 re
W* n
q
107.0929 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 238.6204 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Tetramer)Tj
3.9968 0 Td
(ic)Tj
0.9284 0 Td
(peptide)Tj
3.437 0 Td
(derived)Tj
3.4371 0 Td
(from)Tj
2.1897 0 Td
(bovine)Tj
3.1111 0 Td
(lactoferr)Tj
3.5433 0 Td
(icin)Tj
1.6866 0 Td
(as)Tj
1.2615 0 Td
(treatment)Tj
4.3795 0 Td
(for)Tj
1.3678 0 Td
(oral)Tj
1.8496 0 Td
(squamous)Tj
4.7622 0 Td
(cell)Tj
1.6796 0 Td
(carcinoma)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
81.5811 34.9228 m
237.8835 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(ONE)Tj
2.3669 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https://doi.or)Tj
5.4142 0 Td
(g/10.137)Tj
3.8198 0 Td
(1/journal.po)Tj
5.1236 0 Td
(ne.01747)Tj
4.089 0 Td
(07)Tj
0 g
2.0906 0 Td
(March)Tj
2.9622 0 Td
(30,)Tj
1.5874 0 Td
(2017)Tj
34.3562 0 Td
(2)Tj
0.7654 0 Td
(/)Tj
0.496 0 Td
(17)Tj
/F9 1 Tf
-0.025 Tc
-66.402 84.0904 Td
(a)Tj
0.6448 0 Td
(recipien)Tj
2.8985 0 Td
(t)Tj
0.4748 0 Td
(of)Tj
0.9496 0 Td
(scholarships)Tj
4.9182 0 Td
(from)Tj
2.0055 0 Td
(COLCIENCIA)Tj
4.7339 0 Td
(S)Tj
0.7512 0 Td
(for)Tj
-17.3765 -1.3748 Td
(doctorates)Tj
4.1457 0 Td
(in)Tj
0.8858 0 Td
(Colombia)Tj
3.7276 0 Td
(\(Grant)Tj
2.5724 0 Td
(511-2010\))Tj
3.9261 0 Td
(.)Tj
/F8 1 Tf
-15.2576 -2.126 Td
(Competing)Tj
4.3795 0 Td
(interests)Tj
3.3307 0 Td
(:)Tj
/F9 1 Tf
0.4819 0 Td
(The)Tj
1.5875 0 Td
(authors)Tj
3.0401 0 Td
(have)Tj
1.963 0 Td
(declared)Tj
-14.7827 -1.3749 Td
(that)Tj
1.6228 0 Td
(no)Tj
1.1693 0 Td
(competing)Tj
4.1599 0 Td
(interests)Tj
ET
endstream
endobj
52 0 obj
<>stream
endstream
endobj
53 0 obj
<>stream
endstream
endobj
54 0 obj
<>stream
endstream
endobj
55 0 obj
<>stream
endstream
endobj
56 0 obj
<>stream
endstream
endobj
57 0 obj
<>stream
endstream
endobj
58 0 obj
<>stream
endstream
endobj
59 0 obj
<>stream
endstream
endobj
60 0 obj
<>stream
endstream
endobj
61 0 obj
<>stream
endstream
endobj
62 0 obj
<>stream
endstream
endobj
63 0 obj
<>stream
endstream
endobj
64 0 obj
<>stream
endstream
endobj
65 0 obj
<>stream
endstream
endobj
66 0 obj
<>stream
endstream
endobj
67 0 obj
<>stream
endstream
endobj
68 0 obj
<>stream
endstream
endobj
69 0 obj
<>stream
endstream
endobj
70 0 obj
<>stream
endstream
endobj
71 0 obj
<>stream
endstream
endobj
72 0 obj
<>stream
endstream
endobj
73 0 obj
<>stream
endstream
endobj
74 0 obj
<>stream
endstream
endobj
75 0 obj
<>stream
endstream
endobj
76 0 obj
<>stream
endstream
endobj
77 0 obj
<>stream
endstream
endobj
78 0 obj
<>stream
endstream
endobj
79 0 obj
<>stream
BT
10.3394 79.2147 Td
(exist.)Tj
ET
Q
endstream
endobj
80 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 14 0 R/Annots 82 0 R/Contents 83 0 R/TrimBox[0 0 612 792]>>
endobj
81 0 obj
<>
endobj
84 0 obj
<>
endobj
85 0 obj
<>stream
%!PS-AdobeFont-1.0
11 dict begin
/FontName /TeX_CM_Maths_Symbols def
/FontType 1 def
/FontBBox {-20 -958 1114 770} readonly def
/FontMatrix [0.001 0 0 0.001 0 0] readonly def
/PaintType 0 def
/FontInfo 8 dict dup begin
/FullName (TeX_CM_Maths_Symbols) readonly def
/BaseFontName (TeX_CM_Maths_Symbols) def
end def
/Encoding 256 array
0 1 255 {1 index exch /.notdef put} for
dup 0 /C0 put
dup 1 /C1 put
dup 2 /C2 put
dup 3 /C3 put
dup 4 /C4 put
dup 5 /C5 put
dup 6 /C6 put
dup 7 /C7 put
dup 8 /C8 put
dup 9 /C9 put
dup 10 /C10 put
dup 11 /C11 put
dup 12 /C12 put
dup 13 /C13 put
dup 14 /C14 put
dup 15 /C15 put
dup 16 /C16 put
dup 17 /C17 put
dup 18 /C18 put
dup 19 /C19 put
dup 20 /C20 put
dup 21 /C21 put
dup 22 /C22 put
dup 23 /C23 put
dup 24 /C24 put
dup 25 /C25 put
dup 26 /C26 put
dup 27 /C27 put
dup 28 /C28 put
dup 29 /C29 put
dup 30 /C30 put
dup 31 /C31 put
dup 32 /space put
dup 33 /exclam put
dup 34 /quotedbl put
dup 35 /numbersign put
dup 36 /dollar put
dup 37 /percent put
dup 38 /ampersand put
dup 39 /quoteright put
dup 40 /parenleft put
dup 41 /parenright put
dup 42 /asterisk put
dup 43 /plus put
dup 44 /comma put
dup 45 /hyphen put
dup 46 /period put
dup 47 /slash put
dup 48 /zero put
dup 49 /one put
dup 50 /two put
dup 51 /three put
dup 52 /four put
dup 53 /five put
dup 54 /six put
dup 55 /seven put
dup 56 /eight put
dup 57 /nine put
dup 58 /colon put
dup 59 /semicolon put
dup 60 /less put
dup 61 /equal put
dup 62 /greater put
dup 63 /question put
dup 64 /at put
dup 65 /A put
dup 66 /B put
dup 67 /C put
dup 68 /D put
dup 69 /E put
dup 70 /F put
dup 71 /G put
dup 72 /H put
dup 73 /I put
dup 74 /J put
dup 75 /K put
dup 76 /L put
dup 77 /M put
dup 78 /N put
dup 79 /O put
dup 80 /P put
dup 81 /Q put
dup 82 /R put
dup 83 /S put
dup 84 /T put
dup 85 /U put
dup 86 /V put
dup 87 /W put
dup 88 /X put
dup 89 /Y put
dup 90 /Z put
dup 91 /bracketleft put
dup 92 /backslash put
dup 93 /bracketright put
dup 94 /asciicircum put
dup 95 /underscore put
dup 96 /quoteleft put
dup 97 /a put
dup 98 /b put
dup 99 /c put
dup 100 /d put
dup 101 /e put
dup 102 /f put
dup 103 /g put
dup 104 /h put
dup 105 /i put
dup 106 /j put
dup 107 /k put
dup 108 /l put
dup 109 /m put
dup 110 /n put
dup 111 /o put
dup 112 /p put
dup 113 /q put
dup 114 /r put
dup 115 /s put
dup 116 /t put
dup 117 /u put
dup 118 /v put
dup 119 /w put
dup 120 /x put
dup 121 /y put
dup 122 /z put
dup 123 /braceleft put
dup 124 /bar put
dup 125 /braceright put
dup 126 /asciitilde put
dup 127 /Euro put
dup 128 /ff put
dup 129 /ffi put
dup 130 /ffl put
dup 131 /C131 put
dup 132 /Eth put
dup 133 /eth put
dup 134 /Thorn put
dup 135 /thorn put
dup 136 /onequarter put
dup 137 /onehalf put
dup 138 /C138 put
readonly def
currentdict end
currentfile eexec
M#1H5 J6o\&rtS(#v\0\V7Fe༙OYx5-cY9^%Y6
(efIOldN"wȰ;)UƽoFg/rvV$JS8_oc@
o9-eGJp}[Do]mN=4*{ܯq=eU^t6¤(HwK7X7
Mr:E%]3<Ӝ$wrAQ4ADt%̏>E hAجm*pu@>#6aZi}NRmƼ%
,OgX' EX?ڞ\#JEG<IXS}Eh[ş8ї48ٶ.w4bJ?_nfulqD?둓\C%+' { L9K7isW+ӕ(6oɧVҺlS;5K
Z%.oQՕW*9Qk_S+B-}%lYC@WP0b\KKdi>t,n_S[ '9`-z+cڦEb#c@;yɸoAT O_H~i -6ϰ豟Ae&BF+
wNX!=hhUF8(hZ6pgJc m'9dx*^wXc
գ<.쯶c ln)/LvXY2jbF:ȸ3'>\Ȥmzj,!:ZK' (q/ -&&S ؤ-bm KQSxLGu `D3yԱKaVMU§ %iq5%s 2SdR#ho45H.4TdՊa<K>BqG- Ao, (e&F2gG`z8*༠&
x#B
B;8!93~T/ \>nLazCSKm~,!_<ӾX@X@N2vEt בFmBYa wRG[i;+oM+%(8 jԀlIW>t